Introduction. Mineral Trioxide Aggregate (MTA) is a tricalcium-based silicate, dicalcium silicate matrix. Despite its good biologic properties, some clinicians still claim to have difficulties in handling MTA after its preparation due to its sandy consistency. The aim of the present study was to evaluate the physicochemical properties and cytotoxicity of MTA Repair HP (Angelus, Londrina, PR, Brazil) compared with MTA Angelus (Angelus, Londrina, PR, Brazil). Materials and Method. The properties assessed were particle size, setting time, flow, film thickness, radiopacity, water solubility, compressive strength, and cytotoxicity. Statistical analysis was performed considering p
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Δευτέρα 26 Νοεμβρίου 2018
Physical and Biological Properties of a High-Plasticity Tricalcium Silicate Cement
Massive Haemoptysis due to Obscure Aetiology: Perils and Management Dilemmas
Pulmonary actinomycosis is an important differential diagnosis in patients with long-standing pulmonary infiltrates related to poor oral hygiene or compromised immune function. Up to a quarter of cases of thoracic actinomycosis are misdiagnosed as lung malignancy. Here, we report a 56-year-old man with a hypodense lesion in the left lower lobe presenting with recurrent massive haemoptysis for about one year. He underwent left lower lobe lobectomy due to intractable haemoptysis. Histopathological examination demonstrated actinomycosis infiltrating the left lower lobe. Rarity of the case was the presence of actinomycosis in an immunocompetent individual and without underlying preexisting lung disease. Also, intractable massive haemoptysis necessitating surgical excision which proved to be both diagnostic and curative due to actinomycosis is an unusual occurrence.
https://ift.tt/2PWXltN
Development of a dental handpiece angle correction device
Preparation of a uniform angle of walls is essential for making an ideal convergence angle in fixed prosthodontics. We developed a de novo detachable angle-correction apparatus for dental handpiece drills that...
https://ift.tt/2QtezP7
Pedobarographic analysis of body weight distribution on the lower limbs and balance after ankle arthrodesis with Ilizarov fixation and internal fixation
A number of various techniques were proposed to stabilized ankle arthrodesis, among them external and internal fixation. Appropriate balance and adequate distribution of lower limb loads determine normal biome...
https://ift.tt/2DLNpfj
Beneficial effect of compound essential oil inhalation on central fatigue
Although the physical and mental enhancement effect of essential oils have been proved, the beneficial effect of essential oil in central fatigue remains unclear. In this study, we extracted essential oils fro...
https://ift.tt/2PWAIFH
Effects of transcutaneous electrical nerve stimulation in the Management of Post-Injection Sciatic Pain in a non-randomized controlled clinical trial in Nnewi, Nigeria
Many studies on transcutaneous electrical nerve stimulation (TENS) had been undertaken to explore its pain relieving efficiency on several medicals/surgical conditions but none, specifically, had been carried ...
https://ift.tt/2RbAcjQ
The challenges of muscle biopsy in a community based geriatric population
To describe the difficulties of obtaining muscle samples using a Bergstrom needle technique in a frail older adult population. The data were obtained from a study primarily investigating immunosenescence in fr...
https://ift.tt/2PTCtDE
Utilization and determinants of long term and permanent contraceptive methods among married reproductive age women at Janamora district, northwest Ethiopia
This study is aimed at determining the prevalence and factors associated with utilization of long acting and permanent methods among married reproductive age (15–49) females at Janamora district, in 2018.
https://ift.tt/2PYJbIs
Survival status and predictors of mortality among children with severe acute malnutrition admitted to general hospitals of Tigray, North Ethiopia: a retrospective cohort study
Despite the presence standard protocol for management of severe acute malnutrition case-fatality rates in African hospitals remain unacceptably high. The case in Ethiopia is not different from others. Therefor...
https://ift.tt/2RiICWz
Pain management in living related adult donor hepatectomy: feasibility of an evidence-based protocol in 100 consecutive donors
Living donor hepatectomy (LDH) has important consequences in terms of acute and chronic pain. We proposed an anesthetic protocol based on the best currently available evidence. We report the results of this pr...
https://ift.tt/2PYJ67C
The National Physicians Cooperative: transforming fertility management in the cancer setting and beyond
Future Oncology, Ahead of Print.
https://ift.tt/2Rh6k5N
Incidence of human rabies virus exposure in northwestern Amhara, Ethiopia
Clinical Rabies is a widely distributed almost 100% fatal viral zoonotic disease. Most human rabies cases occur in developing countries, especially in Asia and Africa. It can be prevented by immunization, post...
https://ift.tt/2PYAzSg
Prevalence of chlamydia trachomatis infection among reproductive age women in sub Saharan Africa: a systematic review and meta-analysis
Chlamydia trachomatis is the most common curable sexual transmitted bacterial infection in the world, including Sub-Saharan Africa. There is nil systematic review and meta-analysis on Chlamydia trachomatis infect...
https://ift.tt/2RiFtGf
Histoplasma capsulatum causing sinusitis: a case report in French Guiana and review of the literature
American histoplasmosis is a mycosis caused by Histoplasma capsulatum. A variety of clinical features of histoplasmosis have been commonly described ranging from asymptomatic infections to severe pulmonary infect...
https://ift.tt/2Q04l9p
Cost-Effectiveness of Niraparib Versus Routine Surveillance, Olaparib and Rucaparib for the Maintenance Treatment of Patients with Ovarian Cancer in the United States
Abstract
Objectives
The aim was to evaluate the cost-effectiveness of niraparib compared with routine surveillance (RS), olaparib and rucaparib for the maintenance treatment of patients with recurrent ovarian cancer (OC).
Methods
A decision-analytic model estimated the cost per quality-adjusted life-year (QALY) gained for niraparib versus RS, olaparib, and rucaparib from a US payer perspective. The model considered recurrent OC patients with or without germline BRCA mutations (gBRCAmut and non-gBRCAmut), who were responsive to their last platinum-based chemotherapy regimen. Model health states were: progression-free disease, progressed disease and dead. Mean progression-free survival (PFS) was estimated using parametric survival distributions based on ENGOT-OV16/NOVA (niraparib phase III trial), ARIEL3 (rucaparib phase III trial) and Study 19 (olaparib phase II trial). Mean overall survival (OS) benefit was estimated as double the mean PFS benefit based on the relationship between PFS and OS observed in Study 19. Costs included: drug, chemotherapy, monitoring, adverse events, and terminal care. EQ-5D utilities were estimated from trial data.
Results
Compared to RS, niraparib was associated with an incremental cost-effectiveness ratio (ICER) of US$68,287/QALY and US$108,287/QALY for gBRCAmut and non-gBRCAmut, respectively. Compared to olaparib and rucaparib, niraparib decreased costs and increased QALYs, with a cost saving of US$8799 and US$22,236 versus olaparib and US$198,708 and US$73,561 versus rucaparib for gBRCAmut and non-gBRCAmut, respectively.
Conclusions
Niraparib was estimated to be less costly and more effective compared to olaparib and rucaparib, and the ICER fell within an acceptable range compared to RS. Therefore, niraparib may be considered a cost-effective maintenance treatment for patients with recurrent OC.
https://ift.tt/2Avl7Cu
Myeloablative haploidentical transplantation is superior to chemotherapy for patients with intermediate-risk acute myelogenous leukemia in first complete remission
Purpose: Although myeloablative human leukocyte antigen (HLA) haploidentical hematopoietic stem cell transplantation (haplo-HSCT) following pretransplant ATG and granulocyte colony-stimulating factor (G-CSF) stimulated grafts (ATG+G-CSF) has been confirmed as an alternative to HSCT from HLA-matched sibling donors(MSDs), the effect of haplo-HSCT on postremission treatment of patients with AML with intermediate risk (int-risk AML) who achieved first complete remission (CR1) has not been defined. Experimental Design: In this prospective trial, among 443 consecutive patients aged 16-60 years with newly diagnosed de novo AML with int-risk cytogenetics, 147 patients with molecular int-risk AML who achieved CR1 within two courses of induction and remained in CR1 at 4 months postremission either received chemotherapy (n=69) or underwent haplo-HSCT (n=78). Results: The 3-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher in the haplo-HSCT group than in the chemotherapy group (74.3% vs 47.3%, P=0.0004 and 80.8% vs 53.5%, P=0.0001, respectively). In the multivariate analysis with propensity score adjustment, postremission treatment (haplo-HSCT vs chemotherapy) was an independent risk factor affecting the LFS (HR 0.360, 95% CI 0.163-0.793, P=0.011), OS (HR 0.361, 95% CI 0.156-0.832, P=0.017) and cumulative incidence of relapse (CIR; HR 0.161, 95% CI 0.057-0.459, P=0.001) either in entire cohort or stratified by minimal residual disease after the second consolidation. Conclusions: Myeloablative haplo-HSCT with ATG+G-CSF is superior to chemotherapy as a postremission treatment in patients with int-risk AML during CR1. Haplo-HSCT might be a first-line postremission therapy for int-risk AML in the absence of MSDs.
https://ift.tt/2P4DVxM
Conditional Inactivation of Nf1 and Pten in Schwann Cells Results in Abnormal Neuromuscular Junction Maturation
The neuromuscular junction (NMJ) consists of three components, namely presynaptic motor neurons, postsynaptic muscle fibers and perisynaptic Schwann cells (PSCs). The role of Schwann cells (SCs) in regulating NMJ structural and functional development remains unclear. In this study, mice with conditional inactivation of neurofibromin 1 (Nf1) and phosphatase and tensin homolog (Pten), specifically in SCs, resulted in delayed NMJ maturation that led to delayed muscle growth, recapitulating the muscular dystrophy condition observed in human neurofibromatosis type I syndrome (NF1) patients. Expression levels of NMJ development related molecules such as cholinergic receptor, nicotinic, alpha polypeptide 1 (Chrna1), agrin (Agrn), dystrophin, muscular dystrophy (Dmd), laminin, beta 2 (Lamb2) and dystroglycan 1 (Dag1) were also downregulated. To further explore the molecular alterations in these SCs, NF1- and PTEN-related pathways were analyzed in mutant sciatic nerves. As expected, hyperactive RAS/PI3K/AKT/mTOR signaling pathways were identified, suggesting the importance of these pathways for NMJ development, and subsequent muscle maturation.
https://ift.tt/2RbTVzL
Correction to: Emerging roles of Myc in stem cell biology and novel tumor therapies
In the publication of this article [1] there are three errors.
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Cutaneous B-Cell Lymphoma
Primary cutaneous B-cell lymphomas are non-Hodgkin lymphomas that present in the skin without evidence of extracutaneous involvement at diagnosis. There are 3 types of primary cutaneous B-cell lymphomas: primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma, and primary cutaneous diffuse large B-cell lymphoma, leg-type. Because it is most frequently diagnosed on skin biopsy, intravascular large B-cell lymphoma is commonly included with pcBCL. A complicating factor in diagnosing primary cutaneous B-cell lymphomas is that they can appear histologically identical to their extracutaneous counterparts. This review summarizes the clinical presentation, histopathology, evaluation, treatment, and differential diagnosis of these lymphomas.
https://ift.tt/2PYoxrY
Cutaneous Metastasis
Although rare, cutaneous metastases portend a poor prognosis and are often an indicator of widespread disease. Breast cancer and melanoma are the most common types of cancer that are associated with spread to and within the skin; however, other malignancies, such as lung, colon, head and neck, and hematologic, have been described with a degree of relative frequency. A variety of clinical appearances and syndromes of cutaneous metastases are presented and described in this article. Possible treatment options, including skin-directed therapies and immunotherapies, are also discussed.
https://ift.tt/2Rhi5Jg
Rare Cutaneous T-Cell Lymphomas
Rare lymphoma includes the entities that occur in less than 1% of cases of all lymphomas. Although the percentage is low, there are more than eight lymphomas classified as rare lymphomas. This article describes clinical presentation, diagnosis, prognosis, and management of the most common rare lymphomas, including primary cutaneous γδ T-cell lymphoma, primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, primary cutaneous acral CD8+ T-cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, extranodal NK-/T-cell lymphoma, nasal type, and subcutaneous panniculitis-like T-cell lymphoma.
https://ift.tt/2Rf5dDr
Erratum
For the article on "First-Generation and Second-Generation Bruton Tyrosine Kinase Inhibitors in Waldenström Macroglobulinemia" in the October 2018 issue of Hematology/Oncology Clinics of North America (Volume 32, Issue 5), Dr. M. Lia Palomba's last name was erroneously excluded.
https://ift.tt/2RgfLT3
Mycosis Fungoides and Sézary Syndrome
Cutaneous T-cell lymphomas are a heterogeneous collection of non-Hodgkin lymphomas that arise from skin-tropic memory T lymphocytes. Among them, mycosis fungoides (MF) and Sézary syndrome (SS) are the most common malignancies. Diagnosis requires the combination of clinical, pathologic, and molecular features. Significant advances have been made in understanding the genetic and epigenetic aberrations in SS and to some extent in MF. Several prognostic factors have been identified. The goal of treatment is to minimize morbidity and limit disease progression. However, hematopoietic stem cell transplantation, considered for patients with advanced stages, is the only therapy with curative intent.
https://ift.tt/2RgKT4N
Cutaneous Malignancy
The skin is responsible for protecting us from temperature extremes, ultraviolet radiation, physical injury, and infection. As such, it is a complex and rich organ composed of diverse cell types, which have differentiated from the ectoderm, mesoderm, and neural crest. Malignancies that arise in the skin may originate from keratinocytes, melanocytes, Merkel cells, endothelial cells, adnexal structures, constituents of the connective tissue stroma, and skin-resident immune cells among others. The skin is also a common site for metastasis.
https://ift.tt/2Q0xAbZ
Cutaneous Sarcomas
Cutaneous sarcomas are rare malignancies that may present with a variety of clinical manifestations. This article focuses on 4 of the most common cutaneous sarcomas (Kaposi sarcoma, cutaneous angiosarcoma, dermatofibrosarcoma protuberans, and cutaneous leiomyosarcoma) and reviews clinical, diagnostic, and therapeutic aspects of these rare skin malignancies.
https://ift.tt/2Rh3s95
Cutaneous Melanoma—A Review in Detection, Staging, and Management
Melanoma is an increasingly common cancer in the United States, although mortality has likely stabilized. Diagnosis relies on a skilled practitioner with the aid of dermoscopy and initial local surgical management is a mainstay of treatment. Recent changes in staging emphasize continued use of sentinel lymph node biopsy to aid in prognostication although routine complete lymph node dissection has fallen out of favor. Advances in systemic treatment options, including targeted and immunotherapy, have dramatically changed the treatment paradigm for advanced melanoma and improved outcome. Prevention via sun protection remains a critical tool in efforts to limit the burden of this disease.
https://ift.tt/2PYtMrC
Cutaneous Involvement of Hematologic Malignancies
In reviewing cutaneous manifestations of various hematologic malignancies, the authors focus on secondary cutaneous lymphomas and cutaneous manifestations of histiocyte disorders. Secondary cutaneous lymphomas are defined as skin lesions that develop secondary to infiltration by systemic lymphomas with predominantly extracutaneous involvement. In their review of histiocytic disorders with skin involvement, the authors focus on Langerhans cell histiocytosis and Rosai-Dorfman disease. Their review emphasizes the histology, pathophysiology, clinical presentation, prognosis, and treatments available for these diseases.
https://ift.tt/2Rh3myf
Basal Cell Carcinoma Review
Basal cell carcinoma (BCC) is the most common malignancy and the incidence is rising. BCCs have low mortality but can cause significant morbidity primarily through local destruction. The pathogenesis is linked to the interplay between environmental and patient-derived characteristics. There are multiple therapeutic modalities, and appropriate selection requires knowledge of complications, cosmetic outcomes, and recurrence rates. This article reviews the epidemiology, staging, treatment, and prevention of BCC.
https://ift.tt/2PYo0Gu
A Review of Primary Cutaneous CD30+ Lymphoproliferative Disorders
Primary cutaneous CD30+ lymphoproliferative diseases (LPDs) comprise a range of diseases (LyP, pcALCL, and borderline lesions) with broad histologic and phenotypical characteristics, although they all share the common feature of a favorable prognosis notwithstanding histology suggestive of a high-grade lymphoma. Given their cytomorphologic similarities, accurate diagnosis and workup are needed to differentiate these distinct entities in order to best use novel biologic therapies and avoid aggressive overtreatment. Moreover, although CD30+ LPDs have a favorable prognosis, secondary malignancies should be considered as part of the initial evaluation, and patients should have ongoing surveillance.
https://ift.tt/2RicAtO
Caring for the critically ill patients over 80: a narrative review
There is currently no international recommendation for the admission or treatment of the critically ill older patients over 80 years of age in the intensive care unit (ICU), and there is no valid prognostic se...
https://ift.tt/2FIdUoL
Early immune modulation by single-agent trastuzumab as a marker of trastuzumab benefit
Early immune modulation by single-agent trastuzumab as a marker of trastuzumab benefit
Early immune modulation by single-agent trastuzumab as a marker of trastuzumab benefit, Published online: 27 November 2018; doi:10.1038/s41416-018-0318-0
Early immune modulation by single-agent trastuzumab as a marker of trastuzumab benefithttps://ift.tt/2TOaX8U
Development and validation of a novel risk score for the detection of insignificant prostate cancer in unscreened patient cohorts
Development and validation of a novel risk score for the detection of insignificant prostate cancer in unscreened patient cohorts
Development and validation of a novel risk score for the detection of insignificant prostate cancer in unscreened patient cohorts, Published online: 27 November 2018; doi:10.1038/s41416-018-0316-2
Development and validation of a novel risk score for the detection of insignificant prostate cancer in unscreened patient cohortshttps://ift.tt/2ArYFdL
Multiparametric magnetic resonance imaging in the assessment of anti-EGFRvIII chimeric antigen receptor T cell therapy in patients with recurrent glioblastoma
Multiparametric magnetic resonance imaging in the assessment of anti-EGFRvIII chimeric antigen receptor T cell therapy in patients with recurrent glioblastoma
Multiparametric magnetic resonance imaging in the assessment of anti-EGFRvIII chimeric antigen receptor T cell therapy in patients with recurrent glioblastoma, Published online: 27 November 2018; doi:10.1038/s41416-018-0342-0
Multiparametric magnetic resonance imaging in the assessment of anti-EGFRvIII chimeric antigen receptor T cell therapy in patients with recurrent glioblastomahttps://ift.tt/2TOm2qv
The Norwegian Cognitive impairment after stroke study (Nor-COAST): study protocol of a multicentre, prospective cohort study
Early and late onset post-stroke cognitive impairment (PCI) contributes substantially to disability following stroke, and is a high priority within stroke research. The aetiology for PCI is complex and related...
https://ift.tt/2FFWfhi
Stathmin is required for normal mouse mammary gland development and {Delta}16HER2-driven tumorigenesis
Post-natal development of the mammary gland relies on the maintenance of oriented cell division and apico-basal polarity, both of which are often deregulated in cancer. The microtubule (MT) network contributes to control these processes, however very little is known about the impact of altered MT dynamics in the development of a complex organ and on the role played by MT-interacting proteins such as stathmin. In this study, we report that female stathmin knock-out (STM KO) mice are unable to nurse their litters due to frank impairment of mammary gland development. In mouse mammary epithelial cells, loss of stathmin compromised the trafficking of polarized proteins and the achievement of proper apico-basal polarity. In particular, prolactin receptor internalization and localization was altered in STM KO mammary epithelial cells, leading to decreased protein stability and downmodulation of the Prl/PrlR/STAT5 signaling pathway. Absence of stathmin induced alterations in mitotic spindle orientation, accumulation of mitotic defects, and apoptosis, overall contributing to tissue disorganization and further decreasing the expansion of the mammary epithelial compartment. Loss of stathmin in MMTV-Δ16HER2 transgenic mice decreased the incidence and increased the latency of these very aggressive mammary carcinomas. Collectively, these data identify the essential mammary protein stathmin as pro-tumorigenic and suggest it may serve as a potential therapeutic target in breast cancer.
https://ift.tt/2PThjpj
FDA Approves New Treatment for Acute Myeloid Leukemia
MONDAY, Nov. 26, 2018 -- The U.S. Food and Drug Administration recently announced the approval of Daurismo (glasdegib) tablets for use in combination with a low dose of the chemotherapy cytarabine to treat newly diagnosed acute myeloid leukemia...
https://ift.tt/2DY7Lmx
ACA Coverage Substantial, but Did Not Impact Labor Markets
MONDAY, Nov. 26, 2018 -- Millions of workers gained insurance coverage under the Affordable Care Act (ACA) without adverse effects on labor markets, according to a report published by the Robert Wood Johnson Foundation and the Urban Institute. Using...
https://ift.tt/2ScNvkc
Early Antibiotic Use May Be Tied to Higher Childhood Body Weight
MONDAY, Nov. 26, 2018 -- Antibiotic use in children <24 months of age is associated with a slightly higher body weight at 5 years of age, according to a study published recently in Pediatrics. Jason P. Block, M.D., M.P.H., from Harvard Pilgrim...
https://ift.tt/2E0zX8q
Newborns Infected With Ebola in Congo Outbreak
MONDAY, Nov. 26, 2018 -- Ebola infections in newborns are being reported in the current outbreak of the deadly disease in Congo, the World Health Organization says. In an update late last week, the U.N. health agency said there were 36 new confirmed...
https://ift.tt/2Sdqnlt
Estimated 2.5 Percent of U.S. Children Diagnosed With Autism
MONDAY, Nov. 26, 2018 -- The prevalence of parent-reported autism spectrum disorder (ASD) is estimated at 2.5 percent among U.S. children aged 3 to 17 years, according to a study published online Nov. 26 in Pediatrics. Using data from the nationally...
https://ift.tt/2DZMhpp
One-year molecular surveillance of carbapenem-susceptible A. baumannii on a German intensive care unit: diversity or clonality
A. baumannii is a common nosocomial pathogen known for its high transmission potential. A high rate of carbapenem-susceptible Acinetobacter calcoaceticus-Acinetobacter baumannii (ACB)-complex in clinical specimen...
https://ift.tt/2ArP32z
A seven-Gene Signature assay improves prognostic risk stratification of perioperative chemotherapy treated gastroesophageal cancer patients from the MAGIC trial
Abstract
Background
Following neoadjuvant chemotherapy for operable gastroesophageal cancer, lymph node metastasis is the only validated prognostic variable; however, within lymph node groups there is still heterogeneity with risk of relapse. We hypothesized that gene profiles from neoadjuvant chemotherapy treated resection specimens from gastroesophageal cancer patients can be used to define prognostic risk groups to identify patients at risk for relapse. Patients and methods
The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial (n = 202 with high quality RNA) samples treated with perioperative chemotherapy were profiled for a custom gastric cancer gene panel using the NanoString platform. Genes associated with overall survival (OS) were identified using penalized and standard Cox regression, followed by generation of risk scores and development of a NanoString biomarker assay to stratify patients into risk groups associated with OS. An independent dataset served as a validation cohort. Results
Regression and clustering analysis of MAGIC patients defined a seven-Gene Signature and two risk groups with different OS [hazard ratio (HR) 5.1; P < 0.0001]. The median OS of high- and low-risk groups were 10.2 [95% confidence interval (CI) of 6.5 and 13.2 months] and 80.9 months (CI: 43.0 months and not assessable), respectively. Risk groups were independently prognostic of lymph node metastasis by multivariate analysis (HR 3.6 in node positive group, P = 0.02; HR 3.6 in high-risk group, P = 0.0002), and not prognostic in surgery only patients (n = 118; log rank P = 0.2). A validation cohort independently confirmed these findings. Conclusions
These results suggest that gene-based risk groups can independently predict prognosis in gastroesophageal cancer patients treated with neoadjuvant chemotherapy. This signature and associated assay may help risk stratify these patients for post-surgery chemotherapy in future perioperative chemotherapy-based clinical trials.https://ift.tt/2FF9bUv
Six‐months assessment of a hand prosthesis with intraneural tactile feedback
Abstract
Objective
Hand amputation is a highly disabling event, which significantly affects quality of life. An effective hand replacement can be achieved if the user, in addition to motor functions, is provided with the sensations that are naturally perceived while grasping and moving. Intraneural peripheral electrodes have shown promising results toward the restoration of the sense of touch. However, the long‐term usability and clinical relevance of intraneural sensory feedback have not yet been clearly demonstrated.
Methods
To this aim, we performed a six months clinical study with three trans‐radial amputees who received implants of transverse intrafascicular multichannel electrodes (TIMEs) in their median and ulnar nerves. After calibration, electrical stimulation was delivered through the TIMEs connected to artificial sensors in the digits of a prosthesis to generate sensory feedback, which was then used by the subjects while performing different grasping tasks.
Results
All the subjects, notwithstanding their important clinical differences, reported stimulation‐induced sensations from the phantom hand for the whole duration of the trial. They also successfully integrated the sensory feedback into their motor control strategies while performing experimental tests simulating tasks of real life (with and without the support of vision). Finally, they reported a decrement of their phantom limb pain and a general improvement in mood state.
Interpretation
The promising results achieved with all subjects show the feasibility of the use of intraneural stimulation in clinical settings.
This article is protected by copyright. All rights reserved
https://ift.tt/2PTPGMV
Enzymatic Extraction, Purification, and Characterization of Polysaccharides from Penthorum chinense Pursh: Natural Antioxidant and Anti-Inflammatory
Penthorum chinense Pursh (PCP) is a kind of functional food or medicine for liver protection. In the present work, Plackett-Burman design, steepest ascent method, and response surface methodology (RSM) were employed to obtain maximum total sugar yield. The experimental yield of 6.91% indicated a close agreement with the predicted yield of 7.00% of the model under optimized conditions. The major polysaccharide fraction (PCPP-1a) from PCPP was purified and identified as acidic polysaccharides with a high content of uronic acid (FT-IR, UV, HPGPC). PCPP had similar monosaccharide profile with PCPP-1a but was rich in galacturonic acid (HPLC). Both of PCPP and PCPP-1a possessed strong hydroxyl radical scavenging, DPPH radical scavenging, and Fe2+ chelating activities. Moreover, they were revealed to show strong anti-inflammatory activities by inhibiting NO, TNF-α, and IL-1β release compared to LPS treatment in RAW264.7 cells. These data suggest that the polysaccharides from PCP could be potential natural products for treating ROS and inflammatory-related diseases.
https://ift.tt/2RgLdk2
Survival of Coliform Bacteria in Virgin Olive Oil
Coliform bacteria consist of both nonpathogen commensal and human opportunistic pathogen species isolated from different habitats like animals, man, vegetables, and water. Olives normally carry natural nonpathogenic epiphytic bacteria, but during growth, harvest, and processing, one of the final products, represented by virgin olive oil, can be contaminated with coliform. Present study showed that coliform bacteria can survive and reproduce in virgin olive oil containing low level of phenolic compounds. The laboratory inoculation trials demonstrated that when the bacterium Escherichia coli, isolated from the olives carposphere, was transferred in olive oil containing high polar phenols content, equal to 372 mg caffeic acid equivalent per kg, the survival was completely inhibited after 15 days of storage. On the contrary, the bacterium reproduced quickly when it was inoculated in virgin olive oil samples containing lower concentration of polar phenols. The SDS-PAGE analysis of the E. coli proteins showed different electrophoretic patterns when the bacterium was inoculated in the virgin olive oil with high phenolic compounds content, confirming the strong interaction between the olive oil phenols content and the bacterial wall proteins. The SEM ultrastructural observations confirmed the presence of a more higher number of damaged microbial cells in virgin olive oil rich of polar phenols. This finding needs further studies since, in an era of antibiotic resistance, the development of new strategies to fight unwanted food bacteria is promising way for the future.
https://ift.tt/2PY7Ugi
Is Culprit-Lesion-Only PCI in Cardiogenic Shock Still Better at 1 Year?
Cardiogenic shock occurs in approximately 5% of patients with an acute coronary syndrome — usually, but not always, after ST-segment elevation myocardial infarction. If a large amount of myocardial tissue has become ischemic or injured, pump failure and reduced blood flow to vital organs occur.…
https://ift.tt/2r5Ur77
Lethal Fentanyl and Cocaine Intoxication
To the Editor: The opioid crisis has rapidly transitioned from prescription opioids to heroin and fentanyl. We describe an outbreak of opioid intoxication in patients who had not used opioids previously and who had nonopioid substance-use disorder. Late on a weekend evening, the first 6 patients in…
https://ift.tt/2At0K8X
A Novel Familial Cardiac Arrhythmia Syndrome with Widespread ST-Segment Depression
To the Editor: Several classic cardiac genetic disorders have been identified from specific electrocardiographic (ECG) patterns. Here, we describe five unrelated families, from three different countries, with features that appear to represent a previously unrecognized autosomal dominant syndrome.…
https://ift.tt/2BzaqAD
Application of Cell-free DNA Analysis to Cancer Treatment
Tumor biopsies represent the standard for cancer diagnosis and the primary method for molecular testing to guide the selection of precision therapies. Liquid biopsies, particularly those involving cell-free DNA (cfDNA) from plasma, are rapidly emerging as an important and minimally invasive adjunct…
https://ift.tt/2PUG9VL
Health Care in the 2018 Election
The outcome of the 2018 midterm congressional election is important to the future of health care in the United States. Since 1994, the division between those who identify as Republicans and those who identify as Democrats has grown on a range of domestic policy issues, including many major health…
https://ift.tt/2KyjsAI
Changes in Prevalence of Health Care–Associated Infections in U.S. Hospitals
Health care–associated infections are major threats to the safety of patients in the United States. Rates of selected health care–associated infections have become state and national metrics by which government agencies and consumers evaluate health care quality in hospitals. The National…
https://ift.tt/2TT7nuq
Health Regulation for the Digital Age — Correcting the Mismatch
In January 2018, Amazon, Berkshire Hathaway, and JPMorgan Chase announced that they would be teaming up to "disrupt" the health sector. The news set the health policy world abuzz, overshadowing reports that many tech companies were already entering the health sector. Apple, for example, unveiled an…
https://ift.tt/2BzoPNn
Postpartum Care in the United States — New Policies for a New Paradigm
In April 2018, the American College of Obstetricians and Gynecologists (ACOG) called for a new paradigm for postpartum care in the United States. According to the ACOG committee opinion, postpartum care should be an ongoing, individualized, and woman-centered process, rather than being limited to…
https://ift.tt/2KABFxE
What We Can Do about Maternal Mortality — And How to Do It Quickly
Most Americans take for granted that giving birth in a U.S. hospital will be a safe experience resulting in a healthy mother and baby. However, recent reports in the lay media — an NPR special series called "Lost Mothers: Maternal Mortality in the U.S."; a New York Times article on closures of…
https://ift.tt/2BzPY2O
Becoming a Caregiver — Lessons from My Dad
When I imagined this moment, I always thought that it would crush me. Dad stared at me and then back at the social worker. She stood in the doorway, smiling expectantly. She asked again, more loudly than necessary: "Can you introduce me, Paul?" She'd just started work at the nursing home, and I…
https://ift.tt/2PW5M8S
Immunocytochemistry Based on a Cell-Type-Specific Aptamer for Rapid Immunostaining of Adenocarcinoma Cells in Clinical Serosal Fluids
Abstract
All too often, conventional immunocytochemistry (ICC) via an antibody on cytological samples is limited to a few smears due to scant cellularity. To circumvent these limitations, this study employed a cell-type-specific aptamer as the core tool in ICC protocols for a timely and highly specific ICC diagnosis. S6, an aptamer against A549 lung carcinoma cells, was adopted instead of antibodies in this study for differentiating cancer cells in serosal fluids. Here, we developed three different strategies for discriminating the adenocarcinoma cells in effusion cytology specimens using the S6 aptamer in ICC. These strategies included a biotin-labeled S6 aptamer, an FAM-labeled S6 aptamer, and an activatable S6 aptamer. A total of 112 serosal fluid specimens with known diagnoses were evaluated by all three modes of use of the S6 aptamer. ICC procedures based on biotin-labeled or FAM-labeled S6 aptamers required time-consuming washing to avoid interference from nonspecific adsorption. ICC procedures based on an activatable S6 aptamer probe showed a weak fluorescence signal in the absence of target cells, but the procedures showed a strong fluorescence signal due to alteration of the conformation without any complicated washing steps, in the presence of targets. The specificity and sensitivity are higher in all three different ICC protocols based on the S6 aptamer than those for antibody protocols for differentiating adenocarcinoma cells in clinical effusion cytology. ICC based on cell-type-specific aptamers, instead of on a panel of a set of antibodies, is promising as an auxiliary method for the diagnosis of cancer.
https://ift.tt/2DYGO2e
Complements from the Lung
Foreword. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information by sharing relevant background and reasoning with the reader (regular type). The authors' commentary follows. Stage. A 26-year-old man…
https://ift.tt/2DsVEwW
Changes in Prevalence of Health Care–Associated Infections in U.S. Hospitals
Health care–associated infections are major threats to the safety of patients in the United States. Rates of selected health care–associated infections have become state and national metrics by which government agencies and consumers evaluate health care quality in hospitals. The National…
https://ift.tt/2TT7nuq
Genomic Analysis of Lassa Virus during an Increase in Cases in Nigeria in 2018
Lassa fever is a viral hemorrhagic illness that is endemic to parts of West Africa and causes more than 300,000 cases of illness and 3000 deaths each year. Despite the burden of disease, there is currently no approved vaccine, and the only available pharmacologic therapy is early intravenous…
https://ift.tt/2Sg7kau
Lethal Fentanyl and Cocaine Intoxication
To the Editor: The opioid crisis has rapidly transitioned from prescription opioids to heroin and fentanyl. We describe an outbreak of opioid intoxication in patients who had not used opioids previously and who had nonopioid substance-use disorder. Late on a weekend evening, the first 6 patients in…
https://ift.tt/2At0K8X
Complements from the Lung
Foreword. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information by sharing relevant background and reasoning with the reader (regular type). The authors' commentary follows. Stage. A 26-year-old man…
https://ift.tt/2DsVEwW
Changes in Prevalence of Health Care–Associated Infections in U.S. Hospitals
Health care–associated infections are major threats to the safety of patients in the United States. Rates of selected health care–associated infections have become state and national metrics by which government agencies and consumers evaluate health care quality in hospitals. The National…
https://ift.tt/2TT7nuq
Application of Cell-free DNA Analysis to Cancer Treatment
Tumor biopsies represent the standard for cancer diagnosis and the primary method for molecular testing to guide the selection of precision therapies. Liquid biopsies, particularly those involving cell-free DNA (cfDNA) from plasma, are rapidly emerging as an important and minimally invasive adjunct…
https://ift.tt/2PUG9VL
Macrophage Checkpoint Blockade in Cancer — Back to the Future
Macrophages are an essential component of the tumor microenvironment and have been ascribed a role in cancer-promoting inflammation. Phagocytic cells (a component of innate immunity) mediate first-line resistance against pathogens and, when appropriately activated, can mediate extracellular killing…
https://ift.tt/2Rml43q
CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin’s Lymphoma
Anti-CD20 antibodies such as rituximab are integral components of treatment regimens for virtually all subtypes of B-cell non-Hodgkin's lymphoma. Once these lymphomas become refractory to standard antibody- or chemotherapy-based therapies, the prognosis is poor. The median overall survival among…
https://ift.tt/2PUG5oZ
Author's Response
Thanks again for the further comments. The debate continues and I'm happy that this paper has raised such interest, giving me the occasion to further clarify its meaning.
https://ift.tt/2P4z7bQ
A Rasch Analysis of the Integrated Palliative Care Outcome Scale (IPOS)
Accurate assessment of a patient's palliative care needs is essential for the timely provision of treatment and support. The Integrated Palliative Care Outcome Scale (IPOS) is an ordinal measure possessing acceptable psychometric properties, but its ability to discriminate precisely between individual symptom levels has not been rigorously investigated.
https://ift.tt/2zshMV7
Response to “Hyoscine butylbromide for the management of death rattle: sooner rather than later”
We read with interest the article "Hyoscine Butylbromide for the Management of Death Rattle: Sooner Rather Than Later" by Mercadante et al,(1) comparing pre-emptive hyoscine butylbromide for the management of noisy upper respiratory tract secretions (RTS) in patients in the last days of life with treatment of RTS when they occurred. Previous studies have administered anticholinergic drugs to treat already formed noisy RTS rather than preventing their formation, but anticholinergic drugs are unable to remove secretions already formed.
https://ift.tt/2P4jKQB
Bi‐allelic recessive loss‐of‐function mutations in FIGLA cause premature ovarian insufficiency with short stature
Premature ovarian insufficiency (POI) is a group of heterogeneous disorders characterized by decreased ovarian reserve and increased follicle stimulating hormone (FSH) levels. It is rarely associated with short stature. FIGLA mutations with POI are identified with regards to heterozygosity; till date, only one affected family has been identified with homozygous mutations in FIGLA but without functional evaluation. Here, we described two POI patients from a consanguineous family from China. An 18‐year‐old girl and her sister presented with primary amenorrhea and increased FSH and luteinizing hormone levels, but the sister also presented with short stature and bone age delay. Whole‐genome sequencing analysis identified a recurrent homozygous mutation in the FIGLA gene, c.2T>C (p.Met1Thr), in this family member with POI; this variant was segregated within the pedigree. This change was absent in 382 control subjects, and we did not detect any mutations in 39 other idiopathic POI patients. In vitro functional analysis indicates that the p.Met1Thr mutation does not affect the transcription of the FIGLA gene, but blocks the synthesis of the full‐length FIGLA protein. Our results support the notion that bi‐allelic recessive loss‐of‐function effects of FIGLA contribute to POI patients with short stature and expand the FIGLA‐related phenotypic spectrum.
This article is protected by copyright. All rights reserved.
https://ift.tt/2FInrMw
Phase 2 Study of Radiation Therapy Plus Low Dose Temozolomide Followed by Temozolomide and Irinotecan for Glioblastoma: NRG Oncology RTOG Trial 0420
XXXX tested the adjuvant combination of Irinotecan and temozolomide after initial chemoradiation in a single arm phase II study of newly diagnosed glioblastoma. The doublet regimen given for 12 months is substantially more toxic and does not appear to extend overall survival compared to temozolomide alone given for 6 months, with a potential benefit for the combination regimen only in the best prognostic group, RPA Class III.
https://ift.tt/2BzHtok
Implications of Image-Defined Risk Factors and Primary Site Response on Local Control and Radiation Treatment Delivery in the Management of High Risk Neuroblastoma: Is there a Role for De-escalation of Adjuvant Primary Site Radiotherapy?
We show that successive improvements in systemic therapy have improved local relapse-free survival and overall survival in high-risk neuroblastoma, and reduced the potential need for both local and locoregional therapy. Gross disease may be successfully controlled with primary-site radiotherapy to a dose of 30.6 Gy in the context of modern multi-modality therapy. Finally, we show that International Neuroblastoma Risk Group Image Defined Risk Factors, presence/absence of residual disease, and intensity of systemic therapy may be useful in selecting patients for further primary-site radiotherapy de-escalation in future studies.
https://ift.tt/2BAoD0t
Organs at Risk Considerations for Thoracic Stereotactic Body Radiation Therapy: What Is Safe for Lung Parenchyma?
Data were pooled from published reports to analyze dosimetric and clinical predictors of radiation-induced lung toxicity (RILT) after thoracic stereotactic body radiotherapy. Most reviewed studies report safe treatment for mean combined lung dose ≤ 8 Gy (3-5 fractions) and percent total combined lung V20≤10-15%. Interstitial lung disease is a particular risk factor. More detailed dosimetric and endpoint reporting is needed to facilitate future development of accurate quantitative models of RILT.
https://ift.tt/2KAfwzB
Chest wall toxicity after stereotactic body radiation therapy: a pooled-analysis of 57 studies
This study analyzes the significance of clinical and dosimetric risk factors in relation to chest wall (CW) injury after stereotactic body radiotherapy (SBRT) for lung tumors. Our study shows that female sex, having a tumor to CW distance of <16–25 mm, and the dosimetric parameters of maximal dose to 0.5–5 cc and 30 Gy volume exposure of CW or rib are risk factors that predict CW toxicity.
https://ift.tt/2BAoBFT
Dosimetric Impact of MRI distortions - A study on Head and Neck Cancers
The dosimetric impact of distortions on 21 head and neck cancer MR-only radiotherapy (RT) treatment plans was studied. Distorted CT (dCT) images were obtained by deforming patient CTs (CT) with displacement fields from residual system and patient-induced susceptibility effects. The feasibility of MR-only RT was demonstrated by a dose difference of less than 2% within the target volume for all dosimetric parameters evaluated between dCT and CT treatment plans. Active shimming over entire image volumes reduced distortions due to local B0-field inhomogeneities. However, shimming over user-defined sub-volumes introduced unwanted geometric shifts in nearby regions.
https://ift.tt/2KAfyHJ
A Quantitative Clinical Decision-support Strategy Identifying Which Oropharyngeal Head and Neck Cancer Patients may Benefit the Most from Proton Radiation Therapy
We developed and implemented a data-driven decision support system for identifying those oropharyngeal cancer patients likely to have the greatest benefit from proton therapy. We found that younger patients with p16-positive tumors who smoked ≤10 pack-years were estimated to have the most quality-adjusted life years (QALYs) spared with proton therapy, as compared to photon IMRT. Importantly, the estimated benefit of proton therapy depends strongly on the organ-at-risk doses achievable with photon IMRT.
https://ift.tt/2BAuNxr
Mitigating respiratory motion in radiotherapy: rapid, shallow, non-invasive mechanical ventilation for internal thoracic targets
Motion due to normal respiration increases the volume of healthy tissue irradiated during radiotherapy. The authors propose a simple method to reduce the motion associated with respiration by utilising a standard non-invasive ventilator operated at higher frequencies with reduced ventilation volumes. Results from a healthy subject study demonstrate promise in achieving large reductions in respiratory motion around the lower thoracic and upper abdominal regions. This reduction in motion has the potential to increase access to therapeutic regimes of radiotherapy for a patient cohort that has been traditionally poorly served by radiotherapy.
https://ift.tt/2KzsvRZ
Trends in Radiation Oncology Residency Applicant Interview Experiences and Postinterview Communication
Applicants to radiation oncology residencies previously reported high rates of potential Match violations. A survey was sent to all applicants during the 2018 Match at a single institution and were compared to results from a similar 2016 survey. Respondents in 2018 report that fewer programs are engaging in potential Match violations and more are actively discouraging PIC. Some respondents continue to engage in 'gamesmanship', but more are choosing not to send thank you notes/emails.
https://ift.tt/2KDelzy
Neulasta regimen for the hematopoietic ARS: effects beyond neutrophil recovery
This study aims to characterize the protective effects of Neulasta beyond its well-defined role of myelosuppression reversal following acute radiation exposure. Twenty male Göttingen minipigs irradiated at the LD70/45 were administered with either Neulasta or dextrose vehicle. In addition to improving survival and ameliorating neutropenia, here we report that Neulasta upregulates molecular pathways involved in cardiovascular health, prevents occurrence of endothelial dysfunction, and ameliorates endothelial barrier function.
https://ift.tt/2ByFK2H
More Evidence to Help Guide Decision Making About Aspirin for Primary Prevention
Defining the role of aspirin in the primary prevention of cardiovascular events is challenging because of the close balance between benefits and harms. This commentary discusses the results of 2 large trials, 1 in healthy older adults and 1 in middle-aged and older adults with diabetes, that provide information to assist in decision making regarding the use of aspirin in patients without a history of cardiovascular disease.
https://ift.tt/2RejekP
https://ift.tt/2RejekP
The Burden of Candidate Pathogenic Variants for Kidney and Genitourinary Disorders Emerging From Exome Sequencing
Background:
Exome sequencing is increasingly being used for clinical diagnostics, with an impetus to expand reporting of incidental findings across a wide range of disorders. Analysis of population cohorts can help reduce risk for genetic variant misclassification and resultant unnecessary referrals to subspecialists. Objective:
To examine the burden of candidate pathogenic variants for kidney and genitourinary disorders emerging from exome sequencing. Design:
Secondary analysis of genetic data. Setting:
A tertiary care academic medical center. Patients:
A convenience sample of exome sequence data from 7974 self-declared healthy adults. Measurements:
Assessment of the prevalence of candidate pathogenic variants in 625 genes associated with Mendelian kidney and genitourinary disorders. Results:
Of all participants, 23.3% carried a candidate pathogenic variant, the majority of which were attributable to previously reported variants that have implausibly high allele frequencies. In particular, 25 genes (discovered before the creation of the Exome Aggregation Consortium, a genetic database comprising data from a large control population) accounted for 67.7% of persons with candidate pathogenic variants. After stringent filtering based on allele frequency, 1.4% of persons still had a candidate pathogenic variant, an excessive rate given the prevalence of monogenic kidney and genitourinary disorders. Manual annotation of a subset of variants showed that the majority would be classified as nonbenign under current guidelines for clinical sequence interpretation and could prompt subspecialty referrals if returned. Limitation:
Limited access to health record data prevented comprehensive assessment of the phenotypic concordance with genetic diagnoses. Conclusion:
Widespread reporting of incidental genetic findings related to kidney and genitourinary disorders will require stringent curation of clinical variant databases and detailed case-level review to avoid genetic misdiagnosis and unnecessary referrals. These findings motivate similar analyses for genes relevant to other medical subspecialties. Primary Funding Source:
National Institute of Diabetes and Digestive and Kidney Diseases and National Human Genome Research Institute.https://ift.tt/2PXvB8r
Long-Term Protection After Fractional-Dose Yellow Fever Vaccination Follow-up Study of a Randomized, Controlled, Noninferiority Trial
Background:
Outbreaks of yellow fever and a frequently depleted vaccine stock increase demand for a dose-sparing strategy. A fractional dose of 17D yellow fever virus (17D-YFV) vaccine has been shown to be noninferior to the standard dose in inducing seroprotection. Objective:
To evaluate whether fractional-dose vaccination can confer long-term immunity. Design:
Ten-year follow-up of a subgroup of a randomized, controlled, noninferiority trial. (Dutch Trial Register: NTR7094 [current study] and ISRCTN46326316 [original study]) Setting:
The Netherlands. Participants:
Seventy-five of 155 participants in the original trial provided a blood sample for this study. These 75 participants had received primary vaccination with 17D-YFV vaccine 10 years before. Forty received a 0.1-mL fractional dose intradermally, and 35 received the standard 0.5-mL dose subcutaneously. Measurements:
Virus-neutralizing antibody responses were measured by a plaque reduction neutralization test. Results:
Thirty-nine of 40 (98% [95% CI, 89% to 100%]) participants had protective levels of yellow fever–neutralizing antibodies more than 10 years after receiving a fractional dose of 17D-YFV vaccine compared with 34 of 35 (97% [CI, 87% to 100%]) in the standard-dose group. Limitation:
Only 48% of participants from the original trial participated in this study. Conclusion:
Intradermal administration of a one-fifth dose of yellow fever vaccine induced a protective immune response that lasted for 10 years after vaccination. Persons receiving a fractional dose of yellow fever vaccine do not require a booster vaccination for long-term protection against yellow fever. Primary Funding Source:
Leiden University Medical Center and the International Society of Travel Medicine.https://ift.tt/2RgU9po
Harnessing the Consumer Movement
In this issue, an American College of Physicians (ACP) position paper on Principles for Patient and Family Partnership moves beyond longstanding rhetoric urging clinicians to become more "patient-centered" and calls for an aggressive turn toward true partnership. The editorialists discuss the ACP recommendations and offer their own suggestions for helping to more quickly implement the fundamental changes the ACP advocates.
https://ift.tt/2PW0mKJ
https://ift.tt/2PW0mKJ
Estimated Filtration: The Continued Need for Expert Classification of Genetic Variants
Rasouly and colleagues' study shows that the filters and other automated components of current bioinformatics pipelines alone are insufficient to make a clinically valid determination of whether a genetic variant is disease-causing. The editorialist discusses the findings and the improvements to automated variant interpretation that are needed before entire genomes can be interpreted at scale with clinical validity.
https://ift.tt/2RgTMeu
https://ift.tt/2RgTMeu
Principles for Patient and Family Partnership in Care: An American College of Physicians Position Paper
In this position paper, the American College of Physicians (ACP) examines the rationale for patient and family partnership in care and reviews outcomes associated with this concept, including greater adherence to care plans, improved satisfaction, and lower costs. The paper also explores and acknowledges challenges associated with implementing patient- and family-centered models of care. On the basis of a comprehensive literature review and a multistakeholder vetting process, the ACP's Patient Partnership in Healthcare Committee developed a set of principles that form the foundation for authentic patient and family partnership in care. The principles position patients in their rightful place at the center of care while acknowledging the importance of partnership between the care team and patient in improving health care and reducing harm. The principles state that patients and families should be treated with dignity and respect, be active partners in all aspects of their care, contribute to the development and improvement of health care systems, and be partners in the education of health care professionals. This paper also recommends ways to implement these principles in daily practice.
https://ift.tt/2PWiiVJ
Prospective study of clinical, neurophysiological and urodynamic findings in multiple scleosis patients undergoing percutaneous transluminal venous angioplasty
Multiple Sclerosis (MS) is a multifactorial disease (Lucchinetti et al. 2000; Compston and Cole 2008): perivenular inflammation in the white matter followed by demyelination of central nervous fibers, together with axonal loss and neurodegeneration, contribute to affect sensory (somatic, visual, auditory) motor, cognitive and urinary system functions, leading to increase of disability over time. In animal models, demyelination slows down conduction properties of neural pathways and reduces the ability to transmit neural impulses at high frequency; when combined with axonal degeneration, partial or complete conduction blocks may also occur (McDonald and Sears 1970), leading to functional impairment in virtually all sensory and motor domains.
https://ift.tt/2FHcR8h
De novo temporal intermittent rhythmic delta activity after laser interstitial thermal therapy for mesial temporal lobe epilepsy predicts poor seizure outcome
Temporal intermittent rhythmic delta activity (TIRDA) is an EEG pattern characterized by intermittent rhythmic sinusoidal bursts and trains of delta activity localized over the temporal regions (Cobb, 1945). Unlike other intermittent rhythmic delta activities such as occipital intermittent rhythmic delta activity (OIRDA) and frontal intermittent rhythmic delta activity (FIRDA), TIRDA represents a pre-operative EEG pattern that predicts focal seizures in patients with temporal lobe epilepsy (TLE) (Reiher et al., 1989).
https://ift.tt/2r4POu5
Disruption of Function: Neurophysiological markers of cognitive deficits in retired football players
An estimated 1.6-3.8 million sports-related traumatic brain injuries (TBIs) occur every year in the United States alone (Langlois et al., 2006a; 2006b). An uncomplicated mild-traumatic brain injury (MTBI), more commonly referred to as concussion (Maroon et al., 2000; McCrory et al., 2009; Guskiewicz and Mihalik, 2011; Iverson et al., 2012; Zetterberg and Blennow, 2016), has been described as a serious public health concern (Ommaya and Gennarelli, 1974; Gronwall, 1977; McCrory et al., 2009). Concussion, a "complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces" (McCrory et al., 2009), has been shown to negatively affect cognition, social functioning, emotional wellbeing, and neurologic function years after initial diagnosis (Collins et al., 1991; Dekosky et al., 2010; Kraus et al., 2016).
https://ift.tt/2FJ0h8I
Cortical networks are disturbed in people with cirrhosis even in the absence of neuropsychometric impairment
The term 'hepatic encephalopathy' is used to describe the spectrum of neuropsychiatric change which commonly complicates the course of cirrhosis (Vilstrup et al., 2014). People with cirrhosis with clinically apparent impairment in mental and motor performance, for which there is no other discernible cause, are classified as having overt hepatic encephalopathy. Those with no apparent clinical neuropsychiatric deficits who nevertheless show neuropsychometric or neurophysiological abnormalities are classified as having minimal hepatic encephalopathy (Vilstrup et al., 2014).
https://ift.tt/2r4PQlH
Simultaneously recorded intracranial and scalp high frequency oscillations help identify patients with poor postsurgical seizure outcome
Around one third of patients with focal epilepsy continue to have seizures even after therapy with several different antiepileptic drugs (Kwan and Brodie 2000). In these patients epilepsy surgery aiming to remove the epileptic focus is a very effective treatment to stop seizures permanently (Rosenow and Lüders 2001). In some patients non-invasive diagnostic such as MRI and long-term EEG do not lead to conclusive results regarding the epileptic focus. In these patients intracranial chronic EEG recording may be used to delineate the seizure onset zone (SOZ) and define which brain areas have to be removed to have a good postsurgical seizure outcome (Diehl and Lüders 2000).
https://ift.tt/2FHd0sl
Micturition and startle-induced reflex seizures in a patient with focal cortical dysplasia in the middle frontal gyrus
Reflex seizures arise from hyperexcitable cortex within the areas physiologically activated during specific sensory stimulations, and cognitive or motor activities. Micturition-induced seizures are rare, only a few clinical cases have been reported, all with normal neuroimaging findings, and EEG indicative of fronto-central onset (Whitney and Callen, 2013; Jang et al., 2018). Startle seizures are induced by sudden and unexpected stimuli, usually noise. Most of the patients have widespread structural brain abnormalities, predominantly in the frontal, temporal and perisylvian cortices (Palmini et al., 2005; Yang 2010).
https://ift.tt/2r4Wzfx
Multicenter population pharmacokinetic study of colistimethate sodium and colistin dosed as in normal renal function in patients on continuous renal replacement therapy [Pharmacology]
Background: Intravenous colistimethate sodium (CMS) is used to treat infections with multi-resistant Gram-negative bacteria. Optimal dosing in patients undergoing continuous renal replacement therapy (CRRT) is unclear.
Materials/methods: In a prospective study, we determined CMS and colistin pharmacokinetics in 10 critically ill patients requiring CRRT (8 underwent continuous venovenous hemofiltration (CVVHD), median blood flow 100 ml/min). Intensive sampling was performed on treatment day 1, 3 and 5 after a 9 MU intravenous CMS loading dose (6 MU if body weight < 60 kg) with a consecutive 8-hourly 3 MU (respectively 2 MU) maintenance dose. CMS and colistin were determined by liquid chromatography with mass spectroscopy. A model-based population pharmacokinetic analysis incorporating CRRT settings was applied to the observations.
Results: Sequential model building indicated a monocompartmental distribution for both CMS and colistin, with interindividual variability in both volume and clearance. Hematocrit was shown to affect the efficacy of drug transfer across the filter. CRRT clearance accounted for on average 41% of total CMS and 28% of total colistin clearance, confirming enhanced elimination of colistin compared to normal renal function. Target colistin steady state trough concentrations of at least 2.5 mg/L were achieved in all patients receiving 3 MU 8-hourly.
Conclusion: A loading dose of 9 MU followed after 8 h by a maintenance dosage of 3 MU 8 hourly independent of body weight is expected to achieve therapeutic colistin concentrations in patients undergoing CVVHD using low blood flows. Colistin therapeutic drug monitoring might help to further ensure optimal dosing in individual patients.
https://ift.tt/2Aod0I8
Patients at Risk for Aortic Rupture Often Exposed to Fluoroquinolones During Hospitalization [Epidemiology and Surveillance]
Several studies have indicated that fluoroquinolone use may be associated with an increased risk of aortic aneurysm or dissection (AAD). Because patients with AAD or Marfan syndrome are at increased risk for aortic rupture, we performed a retrospective cohort study to determine the prevalence of systemic fluoroquinolone exposure and predictors of fluoroquinolone use in these patients. Data were obtained from the Advisory Board billing and administrative database, which contained information on 22 million adult hospitalizations in the United States for the study period (2009-2015). International Classification of Diseases (9/10) and Current Procedural Terminology codes were used to identify patients who had AAD or Marfan syndrome or underwent aortic repair. We identified 136,789 admissions for AAD, which involved 99,818 unique patients, 20% of whom received fluoroquinolone during a hospital admission. Of the 7,045 patients with dissection, 18% were exposed to fluoroquinolone. Of the 27,876 AAD patients who underwent aortic repair, 19% received fluoroquinolone during a hospitalization before the repair. In the AAD patients, having a diagnosis of pneumonia or urinary tract infection increased the likelihood of receiving fluoroquinolone during admission by 46% and 40%, respectively (P<0.001). Additionally, we identified 2,871 admissions for Marfan syndrome, which involved 1,872 patients, 14% of whom received fluoroquinolone during an admission. In these patients, pneumonia and urinary tract infections also increased the risk of fluoroquinolone exposure. If the deleterious effects of fluoroquinolone on aortic integrity are substantiated, reducing fluoroquinolone use in hospitalized patients with aortic disorders will become an urgent safety issue for antibiotic stewardship programs.
https://ift.tt/2THnFpY
The global implications of the gentamicin histamine contamination- sorting fact from fiction [Letters]
On the 6th of October 2017 the Therapeutics Goods Administration (TGA) in conjunction with Pfizer Australia released a statement to recall 10 batches of gentamicin Infection BP 80mg in 2ml Steriluer ampoules, due to the finding that these batches may have contained higher than expected amounts of histamine, a residual from the manufacturing process(1)....
https://ift.tt/2AtpC0G
Molecular Analysis of Linezolid Resistant Clinical Isolates of Mycobacterium abscessus [Mechanisms of Resistance]
A total of 194 Mycobacterium abscessus isolates were collected from patients and the whole genomes were sequenced. Eighty-five (43.8%) showed linezolid (LZD) resistant. Only 8.2% of resistant isolates harbored 23S rRNA mutations. qRT-PCR revealed higher transcriptional levels of efflux pumps lmrS and mmpL9 in LZD-resistant isolates. Genome comparative analysis identified several new LZD resistance-associated genes. This study highlights the role of efflux pumps in LZD-resistant M. abscessus and proposes potential target genes for further studies.
https://ift.tt/2TMHTik
In vivo applicability of Neosartorya fischeri antifungal protein 2 (NFAP2) in treatment of vulvovaginal candidiasis [Experimental Therapeutics]
In the consequence of emerging number of vulvovaginitis caused by azole-resistant and biofilm-forming Candida species, the fast and efficient treatment of this infection has become challenging. The problem is further exacerbated by the severe side-effects of azoles as long-term use medications in the recurrent form. There is therefore an increasing demand for novel and safely applicable effective antifungal therapeutic strategies. The small, cysteine-rich and cationic antifungal proteins from filamentous ascomycetes are potential candidates as they inhibit the growth of several Candida spp. in vitro; however no information is available about their in vivo antifungal potency against yeasts. In the present study we investigated the possible therapeutic application of one of their representatives in the treatment of vulvovaginal candidiasis, the Neosartorya fischeri antifungal protein 2 (NFAP2). NFAP2 inhibited the growth of a fluconazole (FLC)-resistant Candida albicans strain isolated from vulvovaginal infection, and it was effective against both planktonic cells and biofilm in vitro. We observed that the fungal cell killing activity of NFAP2 is connected to its pore-forming ability in the cell membrane. NFAP2 did not exert cytotoxic effects on primary human keratinocytes and dermal fibroblasts at the minimal inhibitory concentration in vitro. In vivo murine vulvovaginitis model experiments showed that NFAP2 significantly decreases the cell number of the FLC-resistant C. albicans, and the combined application with FLC enhances the efficacy. These results suggest that NFAP2 provides a feasible base for the development of a fundamental new, safely applicable mono- or polytherapeutic topical agent in the treatment of superficial candidiasis.
https://ift.tt/2AtpvSO
Comparative genomics of serial Candida glabrata isolates and the rapid acquisition of echinocandin resistance during therapy [Mechanisms of Resistance]
The opportunistic pathogen Candida glabrata shows a concerning increase in drug resistance. Here we present the analysis of two serial bloodstream isolates, taken 12 days apart. Both isolates show pan-azole resistance and echinocandin resistance was acquired during the sampling interval. Genome sequencing identified 9 nonsynonymous SNVs between the strains, including a S663P substitution in FKS2 and previously undescribed SNVs in MDE1 and FPR1, offering insight into how C. glabrata acquires drug resistance and adapts to a human host.
https://ift.tt/2TO6Cm5
Emergence of resistance to quinolones and {beta}-lactam antibiotics in enteroaggregative and enterotoxigenic Escherichia coli causing travelers diarrhea. [Epidemiology and Surveillance]
The objective of this study was to assess the antimicrobial resistance of enteroaggregative Escherichia coli (EAEC) and enterotoxigenic E. coli (ETEC) causing traveler's diarrhea (TD) and investigate the molecular characterization of antimicrobial resistance genes to third generation cephalosporins, chepamycins and quinolones. Overall, 39 EAEC and 43 ETEC clinical isolates were studied. The susceptibility of EAEC and ETEC against ampicillin, amoxicillin-clavulanic acid, cefotaxime, imipenem, chloramphenicol, tetracycline, cotrimoxazole, nalidixic acid, ciprofloxacin, azithromycin and rifaximin was determined. All genes encoding resistant determinants were detected by PCR or PCR and DNA sequencing. The epidemiology of selected EAEC and ETEC strains was studied using MLST. The resistance to quinolones of EAEC and ETEC strains causing TD has significantly increased over the last decades, and high percentages has been found especially in patients traveling to India and sub-Saharan Africa. The ST38 and ST131 carrying the blaCTX-M-15 and blaCTX-M-27 genes, respectively, are highly prevalent among ESBL-producing EAEC and ETEC. The cephamycinase ACT-20 is described in the present study for the first time in EAEC and ETEC strains causing TD in patients who had traveled to Central America. The percentages of resistance to azithromycin in EAEC and ETEC isolates from patients to South-East Asia/India and Africa are above 25%. Meanwhile, rifaximin is still active against EAEC and ETEC with the prevalence of resistant strains not being high. In conclusion, fluoroquinolones should no longer be considered the drugs of choice for the prevention or treatment in TD for travelers traveling to India and Africa. Azithromycin and rifaximin are still a good alternative to treat TD caused by EAEC or ETEC.
https://ift.tt/2AobPIw
LEISHMANICIDAL ACTIVITY OF ISOSELENOCYANATE DERIVATIVES. [Chemistry; Biosynthesis]
Conventional chemotherapy against leishmaniasis includes agents exhibiting considerable toxicity. In addition, reports of drug-resistance are not uncommon. Thus, safe and effective therapies are urgently needed. Isoselenocyanate compounds have recently been identified with potential antitumor activity. It is well known that some antitumor agents demonstrate effects against Leishmania. In this study, the in vitro leishmanicidal activities of several organo- selenium and sulfur compounds were tested against Leishmania major and Leishmania amazonensis parasites, using promastigotes and intracellular amastigote forms. The cytotoxicity of these agents was measured in murine peritoneal macrophages and their selectivity indexes were calculated. One of the tested compounds, an isoselenocyanate derivative NISC-6, showed selectivity indexes two- and ten-fold higher than those of the reference drug Amphotericin B when evaluated in L. amazonensis and L. major, respectively. The American strain (L. amazonensis) was less sensitive to NISC-6 than L. major, showing a similar trend as described previously for Amphotericin B. In addition, we also observed that NISC-6 significantly reduced the number of amastigotes per infected macrophage. On the other hand, we showed that NISC-6 decreases expression levels of Leishmania genes involved in the cell cycle, such as topoisomerase-2 (TOP-2), PCNA and MCM4, therefore contributing to its leishmanicidal activity. The effect of this compound on cell cycle progression was confirmed by flow cytometry. We observed a significant increase of cells in the G1 phase and a dramatic reduction of cells in the S phase compared to untreated cells. Altogether, our data suggest that the isoselenocyanate NISC-6 may be a promising candidate for new drug development against leishmaniasis.
https://ift.tt/2TSMMq6
SCY-078, A Novel Fungicidal Agent, Demonstrates Distribution to Tissues Associated with Fungal Infections During Mass Balance Studies with IV and PO 14C-SCY-078 in Albino and Pigmented Rats [Pharmacology]
SCY-078, a fungicidal ß-1,3-glucan synthesis inhibitor, administered as intravenous or oral [14C]-SCY-078 to rat, distributed primarily into tissues associated with invasive fungal disease (kidney, lung, liver, spleen, bone marrow, muscle, vaginal tissue, and skin) to levels exceeding plasma. Oral fraction absorbed was ~40%. Elimination was primarily via bile and feces (~90%) and urine (~1.5%). Mean t1/2 was ~8 h. Quantitative whole-body autoradiography showed a rapid distribution 8 h post-dose, and elimination by 168 h.
https://ift.tt/2Atp7Um
Analysis of Shear Flow-induced Migration of Murine Marginal Zone B Cells In Vitro
https://ift.tt/2r5ATje
RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
https://ift.tt/2FRkgSS
Microfluidic Assay for the Assessment of Leukocyte Adhesion to Human Induced Pluripotent Stem Cell-derived Endothelial Cells (hiPSC-ECs)
https://ift.tt/2r5SyaD
EDTA‐conditioning of circumpulpal dentine induces dentinogenic events in pulpotomized miniature swine teeth
Abstract
Aim
To investigate pulp responses after pulpotomy and EDTA‐conditioning of pulp chamber dentinal walls with or without the placement of a collagenous scaffold in the experimental model of miniature swine teeth.
Methodology
Forty‐two fully developed permanent premolars and molars of healthy miniature swines were used. After preparation of pulp exposures through Class I cavities, the tissue of the pulp chamber was completely removed. The haemorrhage was controlled and the root pulp was protected using a polyurethane film. The circumpulpal pulp chamber dentine was treated for 3 min with normal saline (group 1), or 17% EDTA solution (groups 2 and 3). The film was removed and the pulp chamber cavities were left empty (groups 1 and 2), or filled with swine collagenous sponge (group 3). The access cavities were restored with a Teflon disc and glass ionomer. Teeth were evaluated histo‐morphologically after 10 weeks. Data were compared using the nonparametric Fisher's exact test.
Results
Teeth after treatment of dentine with saline (group 1) were associated with no or only traces of hard tissue formation along the root canal walls. Atubular tertiary dentine deposition in the form of matrix deposition along root canal walls, or dentine bridge formation at the orifice of root canals or complete pulp canal obliteration, were found after treatment of dentine with EDTA in both experiments (groups 2 and 3). Significantly different types of mineralization in the root canals of groups 2 and 3 were seen (p=0.001). Tissue changes in the pulp cavity, characterized by soft tissue growth and osteodentine or atubular tertiary dentine formation, were only seen after EDTA‐conditioning of dentine, in 6.2% of the teeth without scaffold and 64.7% of the teeth with scaffold application. Newly deposited mineralized matrix in the pulp chamber was always in continuation with hard tissue deposited in the root canals.
Conclusions
The EDTA‐conditioning of pulp cavity dentinal walls after pulpotomy induced dentinogenic events in the root pulp. Application of collagenous scaffold in the pulp cavity enhanced soft tissue growth and mineralized tissue formation along the treated circumpulpal dentine.
This article is protected by copyright. All rights reserved.
https://ift.tt/2PZLgE7
Simultaneous Study of the Recruitment of Monocyte Subpopulations Under Flow In Vitro
https://ift.tt/2P49UOC
Decellularization of Whole Human Heart Inside a Pressurized Pouch in an Inverted Orientation
https://ift.tt/2zu70h6
ADT May Up Risk for Heart Failure in Prostate Cancer Patients
MONDAY, Nov. 26, 2018 -- For patients with prostate cancer, androgen deprivation therapy is associated with an increased risk for heart failure, according to a study published online Nov. 7 in the Journal of Clinical Pharmacology. Hui-Han Kao, from...
https://ift.tt/2ztcdWC
CDC: U.S. Prevalence of ALS Was 5.2 Per 100,000 in 2015
MONDAY, Nov. 26, 2018 -- In 2015, the prevalence of amyotrophic lateral sclerosis (ALS) in the United States was 5.2 per 100,000 population, with 16,583 cases identified, according to research published in the Nov. 23 issue of the U.S. Centers for...
https://ift.tt/2zrUjn7
Insulin Needed for T2DM Tx Set to Increase >20 Percent by 2030
MONDAY, Nov. 26, 2018 -- From 2018 to 2030, the insulin required to treat type 2 diabetes is expected to increase more than 20 percent, according to a study published online Nov. 20 in The Lancet Diabetes & Endocrinology. Sanjay Basu, Ph.D.,...
https://ift.tt/2P3iDQY
Ocrelizumab May Help Preserve Hand, Arm Function in PPMS
MONDAY, Nov. 26, 2018 -- For patients with primary progressive multiple sclerosis (PPMS), ocrelizumab reduces progression of upper-extremity (UE) impairment, according to an exploratory analysis published online Nov. 12 in the Multiple Sclerosis...
https://ift.tt/2zqLUQV
Clinical Decision Support System Ups Outpatient PE Management
MONDAY, Nov. 26, 2018 -- The use of a clinical decision support system (CDSS) in the emergency department can improve outpatient management for patients with acute pulmonary embolism (PE), according to a study published online Nov. 13 in the Annals...
https://ift.tt/2P7URDO
Youth Smoking Decline Mirrors Rise in Vaping Popularity
MONDAY, Nov. 26, 2018 -- Even with the rapid rise in popularity of electronic cigarettes, there has been a simultaneous decline in smoking prevalence among U.S. teens and young adults, suggesting e-cigarettes may not prompt young people to start...
https://ift.tt/2ztch8O
Child Overweight, Obesity Linked to Increased Asthma Risk
MONDAY, Nov. 26, 2018 -- Children who are overweight or obese have an increased risk for asthma, according to a study published online Nov. 26 in Pediatrics. James E. Lang, M.D., M.P.H., from Duke University in Durham, North Carolina, and colleagues...
https://ift.tt/2P3rJ0r
Lung Cancer Screening Implementation Guide Developed
MONDAY, Nov. 26, 2018 -- The American Lung Association and the American Thoracic Society have established a website to guide implementation of lung cancer screening, according to an editorial published in the Nov. 1 issue of the American Journal of...
https://ift.tt/2ztcfxI
Obesity Tied to Increased Risk for Early-Onset CRC in Women
MONDAY, Nov. 26, 2018 -- Obesity is associated with an increased risk for early-onset colorectal cancer (CRC) among women, according to a study recently published in JAMA Oncology. Po-Hong Liu, M.D., M.P.H., from Massachusetts General Hospital in...
https://ift.tt/2P47tf4
Probiotics Show No Benefits for Pediatric Acute Gastroenteritis
MONDAY, Nov. 26, 2018 -- For children with acute gastroenteritis, probiotics show no significant benefit versus placebo, according to two studies published in the Nov. 22 issue of the New England Journal of Medicine. David Schnadower, M.D., M.P.H.,...
https://ift.tt/2P3RjSG
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
https://ift.tt/2PZxGAD
Invasive Hemodynamic Monitoring of Aortic and Pulmonary Artery Hemodynamics in a Large Animal Model of ARDS
https://ift.tt/2Rbhby1
IL-4-dependent Jagged1 expression/processing is associated with survival of chronic lymphocytic leukemia cells but not with Notch activation
IL-4-dependent Jagged1 expression/processing is associated with survival of chronic lymphocytic leukemia cells but not with Notch activation
IL-4-dependent Jagged1 expression/processing is associated with survival of chronic lymphocytic leukemia cells but not with Notch activation, Published online: 26 November 2018; doi:10.1038/s41419-018-1185-6
IL-4-dependent Jagged1 expression/processing is associated with survival of chronic lymphocytic leukemia cells but not with Notch activationhttps://ift.tt/2Q0MLCg
Calcimimetic restores diabetic peripheral neuropathy by ameliorating apoptosis and improving autophagy
Calcimimetic restores diabetic peripheral neuropathy by ameliorating apoptosis and improving autophagy
Calcimimetic restores diabetic peripheral neuropathy by ameliorating apoptosis and improving autophagy, Published online: 26 November 2018; doi:10.1038/s41419-018-1192-7
Calcimimetic restores diabetic peripheral neuropathy by ameliorating apoptosis and improving autophagyhttps://ift.tt/2RbgYLf
Chloroquine ameliorates carbon tetrachloride-induced acute liver injury in mice via the concomitant inhibition of inflammation and induction of apoptosis
Chloroquine ameliorates carbon tetrachloride-induced acute liver injury in mice via the concomitant inhibition of inflammation and induction of apoptosis
Chloroquine ameliorates carbon tetrachloride-induced acute liver injury in mice via the concomitant inhibition of inflammation and induction of apoptosis, Published online: 26 November 2018; doi:10.1038/s41419-018-1136-2
Chloroquine ameliorates carbon tetrachloride-induced acute liver injury in mice via the concomitant inhibition of inflammation and induction of apoptosishttps://ift.tt/2PVZ0Qt
Three-dimensional in vitro modeling of malignant bone disease recapitulates experimentally accessible mechanisms of osteoinhibition
Three-dimensional in vitro modeling of malignant bone disease recapitulates experimentally accessible mechanisms of osteoinhibition
Three-dimensional in vitro modeling of malignant bone disease recapitulates experimentally accessible mechanisms of osteoinhibition, Published online: 26 November 2018; doi:10.1038/s41419-018-1203-8
Three-dimensional in vitro modeling of malignant bone disease recapitulates experimentally accessible mechanisms of osteoinhibitionhttps://ift.tt/2RgR6xq
Zinc finger protein 32 promotes breast cancer stem cell-like properties through directly promoting GPER transcription
Zinc finger protein 32 promotes breast cancer stem cell-like properties through directly promoting GPER transcription
Zinc finger protein 32 promotes breast cancer stem cell-like properties through directly promoting GPER transcription, Published online: 26 November 2018; doi:10.1038/s41419-018-1144-2
Zinc finger protein 32 promotes breast cancer stem cell-like properties through directly promoting GPER transcriptionhttps://ift.tt/2PSiKnX
Satisfactory results of a psychometric analysis and calculation of minimal clinically important differences of the World Health Organization quality of life-BREF questionnaire in an observational cohort study with lung cancer and mesothelioma patients
Abstract
Background
To determine the psychometric properties and minimal clinically important differences (MCIDs) of the World Health Organization Quality of Life-BREF (WHOQOL-BREF) in advanced stage lung cancer patients.
Methods
Patients (n = 153) completed the WHOQOL-BREF and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Confirmatory factor analysis (CFA) was performed and reliability and construct validity determined. MCIDs were estimated with two distribution-based methods (0.5 standard deviation (SD) and 1 standard error of measurement (1 SEM)).
Results
CFA confirmed WHOQOL-BREF domain structure. All domains demonstrated good internal consistency (α > 0.70), except Social Relationships (α = 0.57). Nineteen of the 24 WHOQOL-BREF items had correlations of ≥ 0.40 with their intended domain. Four items had higher correlations with a domain other than their intended domain. Moderate to strong correlations were observed for corresponding domains of the two questionnaires, except for the social domains (r = 0.07). For 0.5 SD, MCIDs ranged from 0.88 to 1.55, and for 1 SEM MCIDs ranged from 1.76 to 2.72.
Conclusions
The WHOQOL-BREF has satisfactory psychometric properties in patients with advanced stage lung cancer, whereas the observed MCIDs provide a method for interpretation of scores.
https://ift.tt/2PVcr2N
Tox and Hound – The Worst of Both Worlds
A very special welcome to our newest hound, Jeanna Marraffa, PharmD, DABAT! You can learn more about her here . . . by Jeanna Marraffa Circa Feb 2012 Poison Center: "Um, Jeanna, there is a doc on the line that has a quick question for you. I'm going to send it through to your line." […]
EMCrit Project by Tox & Hound.
https://ift.tt/2ByaY9V
Gain‐of‐function variants in the ODC1 gene cause a syndromic neurodevelopmental disorder associated with macrocephaly, alopecia, dysmorphic features, and neuroimaging abnormalities
Polyamines serve a number of vital functions in humans, including regulation of cellular proliferation, intracellular signaling, and modulation of ion channels. Ornithine decarboxylase 1 (ODC1) is the rate‐limiting enzyme in endogenous polyamine synthesis. In this report, we present four patients with a distinct neurometabolic disorder associated with de novo heterozygous, gain‐of‐function variants in the ODC1 gene. This disorder presents with global developmental delay, ectodermal abnormalities including alopecia, absolute or relative macrocephaly, and characteristic facial dysmorphisms. Neuroimaging variably demonstrates white matter abnormalities, prominent Virchow–Robin spaces, periventricular cysts, and abnormalities of the corpus callosum. Plasma clinical metabolomics analysis demonstrates elevation of N‐acetylputrescine, the acetylated form of putrescine, with otherwise normal polyamine levels. Therapies aimed at reducing putrescine levels, including ODC1 inhibitors, dietary interventions, and antibiotics to reduce polyamine production by gastrointestinal flora could be considered as disease‐modifying therapies. As the ODC1 gene has been implicated in neoplasia, cancer surveillance may be important in this disorder.
https://ift.tt/2RhrhNS
The accuracy of computer‐based diagnostic tools for the identification of concurrent genetic disorders
The increasing use of next‐generation sequencing, especially clinical exome sequencing, has revealed that individuals having two coexisting genetic conditions are not uncommon occurrences. This pilot study evaluates the efficacy of two methodologically distinct computational differential diagnosis generating tools—FindZebra and SimulConsult—in identifying multiple genetic conditions in a single patient. Clinical query terms were generated for each of 15 monogenic disorders that were effective in resulting in the top 10 list of differential diagnoses for each of the 15 monogenic conditions when entered into these bioinformatics tools. Then, the terms of over 125 pairings of these conditions were entered using each tool and the resulting list of diagnoses evaluated to determine how often both diagnoses of a pair were represented in that list. Neither tool was successful in identifying both members of a pair of conditions in greater than 40% of test cases. Disorder detection sensitivity was not homogeneous within a tool, with each tool favoring the identification of a subset of genetic conditions. In view of recent exome sequencing data showing an unexpectedly high prevalence of coexistent monogenic conditions, the results from this pilot study highlight a need for the development of computational tools designed to effectively generate differential diagnoses with consideration of the possibility of coexisting conditions.
https://ift.tt/2PZfPK7
EBV-miR-BART8-3p induces epithelial-mesenchymal transition and promotes metastasis of nasopharyngeal carcinoma cells through activating NF-κB and Erk1/2 pathways
Abstract
Background
Epstein-Barr virus (EBV) is ubiquitously associated with nasopharyngeal carcinoma (NPC). EBV encodes two groups of microRNAs (miRNAs) which are divided into BamHI fragment H rightward open reading frame 1 (BHRF1) and BamHI-A rightward transcripts (BART) microRNAs. EBV miR-BART has been found to be involved in the development and progression of NPC. However, so far the role of EBV-miR-BART8-3p in NPC progression remains unknown. This study aimed to investigate the role of EBV-miR-BART8-3p in NPC and explore the underlying mechanisms.
Methods
miRNA expression was profiled in NPC and normal nasopharyngeal mucosal specimens using miRNA sequencing. EBV-miR-BART8-3p and RNF38 expression was quantified with qPCR assay. The migration, invasion and metastasis of NPC cells were evaluated using CCK-8, colony-forming, wound-healing, and migration and invasion assays. The expression levels of epithelial-mesenchymal transition (EMT)-related markers,metastasis-related markers and NF-κB and Erk1/2 signaling proteins were determined using Western blotting. Tumorigenic assay was performed to evaluate the pulmonary metastatic ability of NPC cells in vivo.
Results
EBV BART miRNAs were highly over-expressed and co-expressed in NPC and might be associated with deactivated immune response in NPC according to the sequencing analysis. EBV-miR-BART8-3p expression was significantly higher in human NPC specimens than in normal nasopharyngeal mucosal specimens. EBV-miR-BART8-3p was found to promote NPC migration, invasion and metastasis, drove an EMT process and upregulated expression of metastasis-related proteins expression in NPC cells. Our data showed EBV-miR-BART8-3p directly targeted RNF38 in NPC cells.
Conclusion
The present study demonstrates that EBV-miR-BART8-3p plays a significant role in inducing EMT and promoting metastasis through directly targeting RNF38 in NPC cells via the activation of NF-κB and Erk1/2 signaling pathways. Our findings suggest that EBV-miR-BART8-3p is a potential therapeutic target for NPC.
https://ift.tt/2Qj28oM
MNAT1 is overexpressed in colorectal cancer and mediates p53 ubiquitin-degradation to promote colorectal cancer malignance
Abstract
Background
MNAT1 (menage a trois 1, MAT1), a cyclin-dependent kinase-activating kinase (CAK) complex, high expresses in various cancers and is involved in cancer pathogenesis. However, mechanisms underlying its regulation in carcinogenesis are unclear.
Methods
The tissue microarray of colorectal cancer (CRC) was used to evaluate MNAT1 expressions in CRC tissues using immunohistochemistry, CRC cell lines were also detected MNAT1 expression using Western-blotting. MNAT1 and shMNAT1 vectors were constructed, and transfected into CRC cells. Cell growths of the transfected cells were observed using MTT and colony formation. The affects of MNAT1 on p53 expression were analyzed using Western-blotting and Real-time PCR. Immunoprecipitation assay was used to analyze the interaction p53 and MNAT1, and Western-blotting was used to test the effects of MNAT1 on p53 downstream molecules. The apoptosis of CRC cells with MNAT1 or shMNAT1 were analyzed using flow cytometry. BABL/c athymic nude mice were used to observe the effect of MNAT1 on CRC cell growth in vivo.
Results
MNAT1 was found to be overexpressed in CRC tissues and cells, and MNAT1 expressions in CRC tissue samples were associated with CRC carcinogenesis and poor patient outcomes. MNAT1-knockin increased CRC cell growth and colony formation, and MNAT1-knockdown dramatically decreased cell motility and invasion. MNAT1 physically interacted with p53, MNAT1 also increased the interaction of MDM2 with p53. Strikingly, MNAT1 mediated p53 ubiquitin-degradation. MNAT1 shortened p53 half-life, and ectopic MNAT1 expression decreased p53 protein stability. Moreover, MNAT1 induced RAD51 and reduced p21, cleaved-caspase3, cleaved-PARP and BAX expression. MNAT1 inhibited CRC cell apoptosis. shMANT1 decreased tumor growths in nude mice following p53 increase.
Conclusion
MNAT1 binds to p53, mediates p53 ubiquitin-degradation through MDM2, increases cell growth and decreases cell apoptosis, and finally promotes CRC malignance. MNAT1 binding to p53 and mediating p53 ubiquitin-degradation axis represents a novel molecular joint in the p53 pathway.
https://ift.tt/2DMoVCV
Genomic insights into the metabolism of ‘Candidatus Defluviicoccus seviourii’, a member of Defluviicoccus cluster III abundant in industrial activated sludge
Abstract
Filamentous cluster III Defluviicoccus (DF3) are known to proliferate and cause bulking issues in industrial wastewater treatment plants. Members of the genus Defluviicoccus are also known to exhibit the glycogen accumulating organism (GAO) phenotype, which is suggested to be detrimental to enhanced biological phosphorus removal (EBPR). Despite the reported negative impact members of the DF3 have on activated sludge wastewater treatment systems, limited research has focused on understanding the physiological traits that allow them to compete in these environments. In this study, a near complete genome of an abundant filamentous DF3 named 'Candidatus Defluviicoccus seviourii' was obtained from a full-scale sequencing batch reactor (SBR) treating winery wastewater. Annotation of the 'Ca. D. seviourii' genome revealed interesting metabolic features that help to understand the abundance of this microorganism in industrial wastewater treatment plants. Their potential for the storage of polyhydroxyalkanoates (PHAs) is suggested to favour these organisms with the intermittent availability of carbon in these systems. An ability to fix nitrogen and take up urea may provide them with an additional advantage with the characteristically high carbon to nitrogen content of industrial wastes. The genome and preliminary findings of this study provide a foundation for further research into these biotechnologically relevant organisms.https://ift.tt/2RdAMO7
Toxin-antitoxin systems shows variability among Mycobacterium tuberculosis lineages
Abstract
The Toxin-Antitoxin (TA) systems are operons involved in the formation of persistent cells and in stress situations in microorganism. TAs are widely distributed in Mycobacterium tuberculosis (MTB). The objective of this study was to determine the distribution and variability of protein sequences of TA systems in seven MTB lineages. Protein prediction on 73 genomes of different lineage was made using Prodigal, and profile hidden Markov models (PHMMs) of 225 reference TA proteins were constructed with HMMER. A homology search was made comparing the predicted proteins to PHMMs. Consecutive proteins that matched PHMMs (forming an operon) were selected. Thereafter, clustering of orthologous genes was made for further mutation scanning through multiple alignments. All proteins found belong to TA type II and IV, and 45 proteins were found completely conserved. Six uncharacterized antitoxins homologous to VapB11, VapB5, VapB45, VapB13, ParD1 and RelB were found. Multiple alignments revealed differences among lineages with specific mutations suitable for genotyping. Significant changes in amino acid sequences caused by frameshift mutations were found in 46 TA proteins.https://ift.tt/2BxJQrN
Evaluation of human trophoblasts and ovine testis cell lines for the study of the intracellular pathogen Brucella ovis
Abstract
Since pathogenic Brucella survive and replicate inside phagocytes, cellular models of infection constitute important tools in brucellosis research. We describe the behavior of B. ovis PA (which causes a type of ovine brucellosis mainly affecting the male reproductive tract) and representative attenuated mutants in two commercially available cell lines of non-professional phagocytes related to Brucella tissue preference: OA3.Ts ovine testis cells and JEG-3 human trophoblasts. In comparison with J774.A1 macrophages and HeLa cells, intracellular bacteria were enumerated at several post-infection time points and visualized by confocal microscopy. Replication of B. ovis in OA3.Ts and JEG-3 cells was equivalent to that observed in J774.A1 macrophages -despite the more efficient internalization in the latter- and better than in HeLa cells. Multiplication and/or survival in all phagocytes was dependent on virB2 and vjbR but independent of cgs, despite the attenuation in mice of the Δcgs mutant. However, Omp25c was required for B. ovis internalization only in HeLa cells, and removal of Omp31 increased bacterial internalization in human HeLa and JEG-3 cells. The results presented here demonstrate variability in the interaction of B. ovis with different host cells and provide advantageous models of non-professional phagocytes to study the intracellular behavior of B. ovis.https://ift.tt/2KxeCUp
Molecular cloning and characterization of a Methyl Parathion Hydrolase from an Organophosphorus-degrading Bacterium, Serratia marcescens MEW06
Abstract
An organophosphorus-degrading bacterium MEW06, which exhibited excellent biodegradation capabilities towards 50 mg/L of methyl parathion (MP), paraoxon, and dimethoate, was isolated from Sand Lake (Wuhan, China) and identified as Serratia marcescens subsp. marcescens based on physiological–biochemical characteristics and a 16S rDNA sequence-based phylogenetic tree. MEW06 genome contains a 31.09-kDa MPH (MPHGM004539) that was 54.9% similar to Pseudomonas sp. WBC-3's MPH. RT–qPCR revealed that mphGM004539 gene expression was significant up-regulated when co-cultured with MP. mphGM004539 without signal peptide (mphGM004539Δsp) was successful cloned and expressed in Escherichia coli BL21 (DE3). Optimized specific enzyme activity of MPHGM004539ΔSP was 5.26 U/mg under 35°C and pH 11.0 conditions when MP as the substrate. Additionally, Co2+, Cd2+and Fe2+ increased the enzyme activity level. MP could be degraded by MPHGM004539ΔSP into p-nitrophenol probably by hydrolyzing the P–O ester bond. Virulence of MP towards Drosophila melanogaster W1118 was reduced by MEW06 or MPHGM004539ΔSP biodegradation. This is the first cloning and characterization of MPH from the organophosphorus-degrading bacterium S. marcescens. MEW06 and its MPH have potential roles in the bioremediation of organophosphorus pesticide-contaminated eco-systems.https://ift.tt/2BycOrv
A newly isolated Enterobacter sp. strain produces 2,3-butanediol during its cultivation on low-cost carbohydrate-based substrates
Abstract
2,3-Butanediol (BDO) is an important platform chemical with wide range of applications in various industries. In the present study, a newly isolated wild Enterobacter sp. strain (FMCC-208) was evaluated towards its ability to produce BDO on media composed of sugars derived from sucrose refinery plant. Optimum values of temperature and pH as well as substrate inhibition were determined through batch experiments. The ability of the strain to convert various monosaccharides was also investigated. Maximum BDO concentration of 90.3 g l−1 and 10 g l−1 of acetoin were obtained during a fed-batch bioreactor experiment in with cane molasses and sucrose were employed as substrates. A high volumetric productivity was noted in a fed-batch experiment using molasses and sucrose as carbon source at T = 37°C, in which 73.0 g l−1 of BDO together with 12.4 g l−1 of acetoin were produced where 1.15 g l−1 h−1 of diol/acetoin were produced. In previously pasteurized media, 70.0 g l−1 of BDO and 5.0 g l−1 of acetoin were produced (yield = 0.39 g g−1). Finally, besides BDO production, growth on molasses was accompanied by non-negligible decolorization (25–35%) of the residue. Therefore the strain is a promising candidate for the conversion of sucrose-based materials into BDO.https://ift.tt/2KAC2bA
Phosphatidylinositide 3-Kinase Contributes to the Anti-Inflammatory Effect of Abutilon crispum L. Medik Methanol Extract
Abutilon crispum L. Medik, better known as bladdermallow, is used as a traditional remedy in India, for its anti-inflammatory effect due to its high content of flavonoids. However, research about its anti-inflammatory effect at the molecular level has not been performed. In this study, we aimed to investigate the mechanism of Abutilon crispum methanol extract (Ac-ME) in inhibiting the inflammatory response by conducting several experiments including cellular and molecular assays. Ac-ME inhibited the production of nitric oxide (NO) in RAW264.7 cells during treatment of LPS and Pam3CSK4 without exhibiting cytotoxicity. Ac-ME also suppressed the mRNA expression of inducible nitric oxide (iNOS) and proinflammatory cytokines such as interleukin (IL)-1β and IL-6. Moreover, Ac-ME was shown to inhibit the NF-κB pathway, according to the luciferase reporter gene assay performed with a NF-κB-Luc construct containing NF-κB-binding promoter regions under MyD88 and TRIF overexpression conditions, and immunoblotting analysis by determining the phospho-form levels of IκBα, IKKα/β, and p85, a regulatory domain of phosphatidylinositide 3-kinase (PI3K). Finally, we observed that the level of phospho-p85 induced by the overexpression of spleen tyrosine kinase (Syk) and Src was decreased by Ac-ME at 200 μg/ml. Therefore, these results suggest that Ac-ME has an anti-inflammatory effect by targeting PI3K in the NF-κB signaling pathway.
https://ift.tt/2DKXkBO
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
