Advanced Healthcare Materials, EarlyView.
https://ift.tt/2J2WEec
Τετάρτη 23 Μαΐου 2018
Development of Inhalable Superparamagnetic Iron Oxide Nanoparticles (SPIONs) in Microparticulate System for Antituberculosis Drug Delivery
Rationale, Opportunities, and Reality of Biosimilar Medications
Biologic therapies for cancer and other disorders contribute to improved outcomes for many patients but also account for a large proportion of health care expenditures. Opportunities for cost containment may emerge as the patents on originator products expire and highly similar agents known as…
https://ift.tt/2IGhQaw
Subscribing to Your Patients — Reimagining the Future of Electronic Health Records
Nearly all U.S. health care systems and many physician practices have by now migrated from paper charts to electronic health records (EHRs). But though this shift could have been a transformative change, current EHRs are largely digital remakes of traditional systems, just as many early motion…
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Doughnuts and Discounts — Changes to Medicare Part D under the Bipartisan Budget Act of 2018
https://ift.tt/2LsYaV8
Case 16-2018: A 45-Year-Old Man with Fever, Thrombocytopenia, and Elevated Aminotransferase Levels
Presentation of Case. Dr. Alyssa Sclafani (Medicine): A 45-year-old man presented to the emergency department of this hospital during the summer with fever, thrombocytopenia, and elevated aminotransferase levels. Three weeks before presentation, fever occurred (with temperatures as high as 40.0°C),…
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Tinea Capitis in a Newborn
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Incidence of Cellulitis among Children with Primary Lymphedema
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Interplay among gut microbiota, intestinal mucosal barrier and enteric neuro-immune system: a common path to neurodegenerative diseases?
Abstract
Neurological diseases, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and multiple sclerosis, are often associated with functional gastrointestinal disorders. These gastrointestinal disturbances may occur at all stages of the neurodegenerative diseases, to such an extent that they are now considered an integral part of their clinical picture. Several lines of evidence support the contention that, in central neurodegenerative diseases, changes in gut microbiota and enteric neuro-immune system alterations could contribute to gastrointesinal dysfunctions as well as initiation and upward spreading of the neurologic disorder. The present review has been intended to provide a comprehensive overview of the available knowledge on the role played by enteric microbiota, mucosal immune system and enteric nervous system, considered as an integrated network, in the pathophysiology of the main neurological diseases known to be associated with intestinal disturbances. In addition, based on current human and pre-clinical evidence, our intent was to critically discuss whether changes in the dynamic interplay between gut microbiota, intestinal epithelial barrier and enteric neuro-immune system are a consequence of the central neurodegeneration or might represent the starting point of the neurodegenerative process. Special attention has been paid also to discuss whether alterations of the enteric bacterial-neuro-immune network could represent a common path driving the onset of the main neurodegenerative diseases, even though each disease displays its own distinct clinical features.
https://ift.tt/2s82noC
Avelumab: A Review in Metastatic Merkel Cell Carcinoma
Abstract
Avelumab (Bavencio®) is a fully human IgG1 monoclonal antibody that is directed against programmed cell death ligand 1 (PD-L1). Avelumab functions as an immune checkpoint inhibitor and has recently been approved in the USA, the EU and Japan for the treatment of metastatic Merkel cell carcinoma (MCC). It is thus the first therapeutic agent specifically approved for use in this indication, and is approved for use independent of line of treatment. Approval for avelumab in metastatic MCC was based on the two-part, single-arm, phase II trial, JAVELIN Merkel 200. In Part A of the study, confirmed objective responses were observed in approximately one-third of patients with chemotherapy-refractory metastatic MCC treated with avelumab. The responses were observed early and appeared to be durable, with an estimated 74% of responses having a duration ≥ 12 months. Furthermore, interim results from a separate cohort of patients (Part B) indicate an objective response rate for avelumab of > 60% in patients who were chemotherapy-naïve in the metastatic disease setting. Avelumab is associated with a risk of immune-related adverse events but, overall, has an acceptable and manageable safety and tolerability profile. In conclusion, currently available data suggest that avelumab presents a clinically beneficial new treatment option for metastatic MCC, a rare but aggressive cancer associated with a poor prognosis. 
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Odd‐skipped related 1 inhibits lung cancer proliferation and invasion by reducing Wnt signaling through the suppression of SOX9 and β‐catenin
Cancer Science, EarlyView.
https://ift.tt/2IILaZM
Stromal immunoglobulin κC expression is associated with initiation of breast cancer in TA2 mice and human breast cancer
Cancer Science, EarlyView.
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Efficacy and safety of 3‐month dosing regimen of degarelix in Japanese subjects with prostate cancer: A phase III study
Cancer Science, EarlyView.
https://ift.tt/2xeabe2
Management of Non-Diffuse Large B Cell Lymphoma Post-Transplant Lymphoproliferative Disorder
Opinion statement
Post-transplant lymphoproliferative disorder (PTLD) is one of the most common neoplasms seen after solid organ and hematopoietic stem cell transplantation, and is associated with significant morbidity and mortality. The pathogenesis is related to post-transplant immunosuppression and EBV infection. Prevention of PTLD depends upon judicious use of immunosuppression and serial EBV monitoring. Preemptive therapy consists of reduction of immunosuppression, antiviral medications, and single-agent rituximab. There are no randomized phase III trials on PTLD treatment, so current management guidelines are largely based on recent phase II trials, single-institution retrospective studies, and expert opinion. Management of PTLD is dependent upon its subtypes. Early-type and polymorphic PTLD generally respond to reduction of immunosuppression and rituximab monotherapy, whereas monomorphic PTLD often requires additional concurrent or sequential use of chemotherapy. For rare subtypes of PTLD, standard-of-care guidelines for de novo lymphomas are recommended. Surgical resection or radiotherapy may be used as adjunctive therapy depending on the extent of disease. Non-chemotherapy options such as adoptive T cell therapy have shown promising efficacy and must be explored further. Despite progress in the last decade, overall survival rates continue to be low in published series. This review highlights the need for prospective randomized trials incorporating novel agents to improve outcomes in PTLD.
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Follicular Lymphoma: Past, Present, and Future
Opinion statement
Even in the modern era, follicular lymphoma (FL) remains largely an incurable but treatable disease with both standard and novel treatment modalities. Despite the abundance of efficacious treatment modalities currently available, there is no universally agreed upon standard approach to treatment for patients with FL, particularly in the relapsed/refractory (R/R) setting. There is an increasing need for better tools to risk-stratify patients and to identify those likely to experience relapse early. Additionally, the use of gene expression profiling and next-generation sequencing techniques in recent years has led to a wealth of knowledge regarding the molecular drivers of lymphomagenesis; however, much of this knowledge is not currently applicable on a day to day basis in the clinic setting. Further studies are needed to determine a validated, clinically relevant predictive model that incorporates patient factors and molecular factors that will guide clinicians on the most effective treatment strategy. With many questions left unanswered, it is our opinion that the treatment of FL and sequencing of therapy in the R/R setting should be a personalized approach that balances patient-specific factors such as preferences and comorbidities with treatment-related factors such as known response rates and toxicity profiles.
https://ift.tt/2ILBcah
Quality Assurance and Improvement in Head and Neck Cancer Surgery: From Clinical Trials to National Healthcare Initiatives
Opinion statement
It is without question in the best interest of our patients, if we can identify ways to improve the quality of care we deliver to them. Great progress has been made within the last 25 years in terms of development and implementation of quality-assurance (QA) platforms and quality improvement programs for surgery in general, and within this context for head and neck surgery. As of now, we have successfully identified process indicators that impact outcome of our patients and the quality of care we deliver as surgeons. We have developed risk calculators to determine the risk for complications of individual surgical patients. We have created perioperative guidelines for complex head and neck procedures. We have in Europe and North America created audit registries that can gather and analyze data from institutions across the world to better understand which processes need change to obtain good outcomes and improve quality of care. QA platforms can be tested within the clearly defined environment of prospective clinical trials. If positive, such programs could be rolled out within national healthcare systems, if feasible. Testing quality programs in clinical trials could be a versatile tool to help head neck cancer patients benefit directly from such initiatives on a global level.
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Patterns of RSA and observed distress during the still‐face paradigm predict later attachment, compliance and behavior problems: A person‐centered approach
Developmental Psychobiology, EarlyView.
https://ift.tt/2kmuNrA
Editorial: faecal incontinence—the hidden burden of inflammatory bowel diseases
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 12, Page 1715-1716, June 2018.
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Editorial: validating reliability of the eosinophilic oesophagitis histological scoring system (EOE‐HSS)—an important first step. Authors’ reply
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 12, Page 1714-1715, June 2018.
https://ift.tt/2kpcQZv
Letter: serum HBcrAg is a useful marker for disease monitoring, predicting treatment response and disease outcome of chronic hepatitis B virus infection—authors' reply
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 12, Page 1720-1721, June 2018.
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Editorial: faecal incontinence—the hidden burden of inflammatory bowel diseases. Authors' reply
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 12, Page 1716-1717, June 2018.
https://ift.tt/2J3cKnZ
Editorial: finding the coeliacs – should everyone be screened?
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 12, Page 1717-1718, June 2018.
https://ift.tt/2s8OoPl
Letter: serum HBcrAg is a useful marker for disease monitoring, predicting treatment response and disease outcome of chronic hepatitis B virus infection
Alimentary Pharmacology &Therapeutics, Volume 47, Issue 12, Page 1719-1720, June 2018.
https://ift.tt/2kk0XUv
Matrix Metalloproteinases and Their Tissue Inhibitors in Blood Serum of Patients with Endometrial Cancer: Clinical and Morphological Correlations
In patients with endometrial cancer (N=94), endometrial polyps (N=28), endometrial hyperplasia (N=25), and healthy women (N=77), the serum contents of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 were measured by ELISA. Both carcinoma and benign neoplasms were accompanied by significant elevation of MMP-7 and TIMP-2 in blood serum. The greatest elevation (in comparison with the control) was observed for MMP-7, although serum concentration of this marker was practically identical in patients with carcinoma and benign tumors. In contrast, the levels of MMP-2 and TIMP-1 were lower in cancer patients in comparison with the control; in these patients, the levels of MMP-9 and TIMP-1 were also lower than the corresponding levels in patients with polyps and endometrial hyperplasia. There were no significant correlations between the levels of examined markers with tumor metastasizing, its histological structure, and differentiation degree of endometrial cancer. No differences were observed between examined serological markers in patients with polyps and endometrial hyperplasia of various severities. The examined MMPs and TIMPs cannot be advanced as potential diagnostic markers of endometrial cancer, but they can be used to monitor and prognosticate the disease and to assess effectiveness of the targeted therapy.
https://ift.tt/2x90Cx1
Preventive Effects of Oxidized Dextran on Functional Activity of Pulmonary Macrophages in Mice Infected with Influenza A Virus
We analyzed cytokine profile of pulmonary macrophages in mice infected with highly pathogenic influenza A/H5N1 virus after preventive injections of oxidized dextran. Light microscopy, immunohistochemistry, and morphometric examinations showed that preventive injections of oxidized dextran led to more effective virus elimination, modulation of the proinflammatory cytokine response, and host antiviral response and reduce animal mortality. Our findings allow recommending oxidized dextran for further studies in order to create a vaccine with antiviral and adjuvant potencies.
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Correction to Comparative Study of Toxicity of Alkoxyamines In Vitro and In Vivo
The author name M. V. Edeeva should read M. V. Edeleva.
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In Vitro Effects of Sodium Nitroprusside and L-N ω -Nitroarginine Methyl Ester (L-NAME) on Activity of Lysosomal Cysteine Proteinases and Lysosomal Membrane Permeability
The direct effect of 5 mM L-NAME and 0.1 mM sodium nitroprusside on activity of lysosomal cysteine proteinases and permeability of lysosomal membrane was studied in vitro after 1, 2, and 4 h of incubation. Isolated from the liver of intact female rats lysosome suspensions were used. Both substances reduced total activity of cathepsin H and did not affect cathepsin B at all time intervals. L-NAME increased cathepsin L activity at all incubation times, while sodium nitroprusside increased activity of this enzyme after 2-h incubation and reduced it incubation after 4-h incubation. L-NAME demonstrated a membrane-destabilizing effect in in vitro experiments, while sodium nitroprusside on the contrary stabilized lysosomal membranes.
https://ift.tt/2IG2UsY
Protective Role of Nitrate/Nitrite Reductase System during Transient Global Cerebral Ischemia
The effects of a non-selective blocker of NO synthases LNNA in a dose of 25 mg/kg and nitrates KNO3, NaNO3, Mg(NO3)2, and Ca(NO3)2 in doses of 5 and 50 mg/kg were studied on the model of experimental ischemic stroke induced by bilateral occlusion of the common carotid arteries. Wistar rats were randomized into 40 treatment (n=960) and 8 control (n=192) groups. Treatment group rats received injection of either nitrate, or LNNA, or a combination LNNA+nitrate. All substances were administered intraperitoneally 1 h prior to brain ischemia or 5 sec after occlusion of the common carotid arteries. Control rats received the same volume of 0.9% NaCl at the same terms. The non-selective inhibitor of NO synthases LNNA administered against the background of brain ischemia increased neurological deficit and animal mortality. Nitrate/nitrite reductase system had protective properties depending on the cation of nitrate and concentration of a nitrate during inhibition of NO synthase system under conditions of brain ischemia and hypoxia.
https://ift.tt/2x4DO1z
Endothelial Cells Modulate Differentiation Potential and Mobility of Mesenchymal Stromal Cells
We studied the effect of endothelial cells on in vitro migration and differentiation potential of multipotent mesenchymal stromal cells. Down-regulation of stemness genes OCT4, SOX2, and chondrogenic differentiation regulator SOX9 gene and upregulation of osteogenesis master-gene RUNX2 in mesenchymal stromal cells were observed in the presence of intact and TNFα-activated endothelial cells, which indicated an increase in commitment of mesenchymal stromal cells.The medium conditioned by endothelial cells stimulated migration activity of mesenchymal stromal cells; migration rate increased significantly in conditioned medium from activated cells in comparison with medium from non-activated cells. It was concluded that the interaction with endothelial cells modulated functional activity of mesenchymal stromal cells; moreover, activated endothelial cells produced more pronounced effects on differentiation potential and migration activity of mesenchymal stromal cells both in direct contact and through paracrine regulation.
https://ift.tt/2IFhhh2
Reinforced Hybrid Collagen Sponges for Tissue Engineering
We created an anisotropic material based on collagen sponge and reactive polylactide structured by laser photopolymerization. The combination of collagen with reactive polylactide improves the resistance of the formed matrices to biodegradation in comparison with collagen sponge, while the existence of sites with different mechanical characteristics and cell affinity on the matrix provides directed cell growth during their culturing. It was shown that reinforcement of the collagen sponges 7-fold increased the mean Young's modulus for the hybrid matrix without affecting its cytotoxicity. The developed matrix provides cell adhesion and proliferation along reinforcement lines and can be used for fabrication of tissue engineering constructs.
https://ift.tt/2xdCUQy
Composition of the Stabilizer and Conditions of Lyophilization for Preserving Infectious Activity of Influenza Virus
For stabilization of vaccine preparations, they are lyophilized. The composition of the protective medium is an important parameter affecting the quality of the vaccine after drying. In view of the risk of spreading prion diseases, the use of media containing animal proteins is not recommended. In this study, protective media containing no animal proteins and lyophilization regimen were determined. The optimum lyophilization regimen consisted of three stages: freezing at -70°C, main stage at -35°C, and drying at 24°C. Protective medium containing 4% trehalose or protective medium with 10% sucrose and 5% soy peptone ensured highest stability of the lyophilized vaccine preparation in temperature range of 4-24°C. This can help to overcome possible break in the cold chain, which is important during transporting or storage of vaccine preparations.
https://ift.tt/2Ls40X4
Isolation of Rat Olfactory Ensheathing Cells and Their Use in the Therapy of Posttraumatic Cysts of the Spinal Cord
We evaluated the efficacy of rat olfactory ensheathing cells in the therapy of experimental cysts of the spinal cord. Improvement of the motor function of the hind limbs after transplantation of the olfactory ensheathing cells into the posttraumatic spinal cord cysts rats was found. We also determined the required number of cells for transplantation and demonstrated a neuroprotective effect of this dosage. For further clinical studies, autologous tissue-specific cell preparation of olfactory ensheathing cells has to be created. Cell therapy in combination surgical and pharmacological treatment will substantially improve the quality of life of patients with posttraumatic spinal cord cysts.
https://ift.tt/2x4zsHS
Retinoblastoma Cell Culturing and Evaluation of Their Drug Resistance
We obtained primary culture of retinoblastoma cells and evaluated the resistance of cultured ells to chemotherapy. The study included 19 patients aged 6-64 months (mean 27.9±17.4 months); of these, 6 (31.6%) patients with bilateral retinoblastoma and 13 (68.4%) patients with unilateral form. In 18 (94.7%) patients, group E retinoblastoma was diagnosed. Enucleation was performed in all patients; in 94.7% cases, low-differentiated retinoblastoma was identified. Samples of the tumor tissue were taken to derive a cell culture and to study drug resistance and metabolic activity of cells (MTT test). In 4 cases, adhesion primary cultures of retinoblastoma were derived. Cytological verification of the obtained cultures was performed. The primary cultures were derived from 4 of 6 bilateral tumors and from none of 13 unilateral tumors (p=0.003). There were no statistically significant correlations with patient age (p=0.33) and the presence of calcifications in the tumor (p=0.26). MTT test revealed no differences in the sensitivity of cell cultures to irinotecan and ifosfamide. Pronounced differences in the resistance of cell cultures were observed for oxaliplatin and ascorbic acid. MTT test with evaluation of drug resistance can be used both in clinical practice for adjusting chemotherapy regimen and in development of new approaches to the treatment of retinoblastoma with assessment of in vivo tumor cell resistance in animal models.
https://ift.tt/2LmT0Km
Peculiarities of Molecular Mechanisms Involved in Modification of the Structural and Molecular Organization of the Cell Genome
Within the framework of the previously proposed model of structural organization of DNA that supplements the Watson—Crick model and is based on a mathematical regulation — Fibonacci sequence, we suppose the existence of nucleotides without nitrogenous base and acting as linkers connecting DNA subunits.
https://ift.tt/2x4zbEQ
Heart Rhythm Disturbances Caused by Injection of Cholinesterase Inhibitor Physostigmine to Rats during the Early Ontogeny
Parameters of cardiac activity after administration of the cholinesterase inhibitor physostigmine were analyzed in newborn rats and on day 16 of postnatal development. The type of cardiovascular response to acetylcholine excess in newborns and 16-day-old rats were similar, but they significantly differed by the magnitude, which suggests that that maturation of cholinergic structures involved in the regulation of cardiac activity is completed during the early postnatal ontogeny.
https://ift.tt/2Ls3J6u
Effect of Intramuscular Administration of Mesenchymal Stem Cells and Erythropoietin on Angiogenesis in Critical Limb Ischemia
We studied the effect of intramuscular injections of bone marrow mesenchymal stromal cells on microcirculation parameters in an ischemic limb of Wistar rats. It was shown that transplantation of mesenchymal stem cells with or without erythropoietin stimulates angiogenesis in the ischemic zone. An essential role in angiogenesis stimulation is played by cytokines and growth factors.
https://ift.tt/2ILqyQR
Radioprotective Properties of Neomitilan in Experimental Radiation Pneumonia
The efficiency of neomitilan, a polysaccharide isolated from Crenomytilus grayanus mussels, was studied in experimental model of radiation pneumonia (irradiation of the animal lungs with a total dose of 14 and 28 Gy). Histological study showed that an increase in the number of nucleated components in the lungs of animals subjected to neomitilan inhalation prior to irradiation. Proliferation of bronchial epitheliocytes and the formation of additional lymphoid structures were also revealed in these animals. The absence of a tendency to lung tissue recovery in animals irradiated with 28 Gy is due to extreme radiation toxicity.
https://ift.tt/2IGLfRV
Cell Death and Development of Fibrotic Alterations in Lung Granuloma of BALB/c Mice during Chronic BCG-Induced Granulomatosis
Light microscopy, immunohistochemistry, and morphometric examinations established that cell death in lung granulomas of BCG-infected mice resulted mainly from activation of receptor-mediated apoptosis, which did not prevent the persistence of the causative agent in macrophages of the granulomas and promoted the formation of pronounced fibrosis in granulomas and pulmonary interstitium.
https://ift.tt/2IIxQEK
Dynamics of Expression of Cytokine Genes and Macrophage Content in the Lungs and Kidneys after Subtotal Hepatectomy in Rats
The role of the lungs and kidneys in liver regeneration after subtotal hepatectomy was studied on a rat model. It was found that production of hepatocyte growth factor (HGF) in the lungs and kidneys and expression of cytokine genes Il1b, Il6, Il10, and tnfa significantly increased. Analysis of the dynamics of lung macrophage population showed that accumulation of HGF and the increase in the expression of cytokine genes in the lungs were accompanied by simultaneous increase in the number of CD68+ cells, which attested to the leading role of macrophages in activation of HGF synthesis in the lungs. Macrophage content in the kidneys after subtotal hepatectomy did not increase.
https://ift.tt/2IGeggx
Quantification of near‐wall hemodynamic risk factors in large‐scale cerebral arterial trees
International Journal for Numerical Methods in Biomedical Engineering, EarlyView.
https://ift.tt/2KRC7Xp
Absence of KRAS hotspot mutations in endometriosis of Korean patients
Histopathology, EarlyView.
https://ift.tt/2KLKofl
Antegrade tissue scraping through endoscopic ultrasonography‐guided hepaticogastrostomy (with video)
Digestive Endoscopy, EarlyView.
https://ift.tt/2kjMGqP
Comprehensive profiling of DNA repair defects in breast cancer identifies a novel class of endocrine therapy resistance drivers
Purpose: This study was undertaken to conduct a comprehensive investigation of the role of DNA damage repair (DDR) defects in poor outcome ER+ disease. Experimental Design: Expression and mutational status of DDR genes in ER+ breast tumors were correlated with proliferative response in neoadjuvant aromatase inhibitor therapy trials (discovery data set), with outcomes in METABRIC, TCGA and Loi data sets (validation data sets), and in patient derived xenografts. A causal relationship between candidate DDR genes and endocrine treatment response, and the underlying mechanism, was then tested in ER+ breast cancer cell lines. Results: Correlations between loss of expression of three genes: CETN2 (p<0.001) and ERCC1 (p=0.01) from the nucleotide excision repair (NER) and NEIL2 (p=0.04) from the base excision repair (BER) pathways were associated with endocrine treatment resistance in discovery data sets, and subsequently validated in independent patient cohorts. Complementary mutation analysis supported associations between mutations in NER and BER pathways and reduced endocrine treatment response. A causal role for CETN2, NEIL2 and ERCC1 loss in intrinsic endocrine resistance was experimentally validated in ER+ breast cancer cell lines, and in ER+ patient-derived xenograft models. Loss of CETN2, NEIL2 or ERCC1 induced endocrine treatment response by dysregulating G1/S transition, and therefore, increased sensitivity to CDK4/6 inhibitors. A combined DDR signature score was developed that predicted poor outcome in multiple patient cohorts. Conclusions:This report identifies DDR defects as a new class of endocrine treatment resistance drivers and indicates new avenues for predicting efficacy of CDK4/6 inhibition in the adjuvant treatment setting.
https://ift.tt/2kmk3JH
Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor-Positive Advanced Breast Cancer
Purpose: This single-arm, open label Phase II study evaluated the safety and efficacy of taselisib (GDC-0032) plus fulvestrant in postmenopausal women with locally advanced or metastatic HER2-negative, hormone receptor (HR)-positive breast cancer. Experimental Design: Patients received 6 mg oral taselisib capsules daily plus intramuscular fulvestrant (500 mg) until disease progression or unacceptable toxicity. Tumor tissue (if available) was centrally evaluated for PIK3CA mutations. Adverse events (AEs) were recorded using NCI-CTCAE v4.0. Tumor response was investigator-determined using RECIST v1.1. Results: Median treatment duration was 4.6 (range: 0.9-40.5) months. All patients experienced ≥1 AE, 30 (50.0%) had grade ≥3 AEs, and 19 (31.7%) experienced 35 serious AEs. Forty-seven of sixty patients had evaluable tissue for central PIK3CA mutation testing (20 had mutations, 27 had no mutation detected [MND]). In patients with baseline measurable disease, clinical activity was observed in tumors with PIK3CA mutations (best confirmed response rate: 38.5% [5/13; 95% CI 13.9-68.4]; clinical benefit rate [CBR]: 38.5% [5/13; 95% CI 13.9-68.4]), PIK3CA-MND (best confirmed response rate: 14.3% [3/21; 95% CI 3.0-36.3]; CBR: 23.8% [5/21; 95% CI 8.2-47.2]), and unknown PIK3CA mutation status (best confirmed response rate: 20.0% [2/10; 95% CI 2.5-55.6]; CBR: 30.0% [3/10; 95% CI 6.7-65.2]). Conclusions: Taselisib plus fulvestrant had clinical activity irrespective of PIK3CA mutation status, with numerically higher objective response rate and CBR in patients with PIK3CA-mutated (versus -MND) locally advanced or metastatic HER2-negative, HR-positive breast cancer. No new safety signals were reported. A confirmatory Phase III trial is ongoing.
https://ift.tt/2xa3I40
BET inhibition overcomes receptor tyrosine kinase-mediated cetuximab resistance in HNSCC
Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to the emergence of intrinsic and acquired resistance. We and others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK) including HER3, MET, and AXL. In an effort to overcome cetuximab resistance and circumvent toxicities associated with the administration of multiple RTK inhibitors, we sought to identify a common molecular target that regulates expression of multiple RTK. Bromodomain-containing protein-4 (BRD4) has been shown to regulate the transcription of various RTK in the context of resistance to PI3K and HER2 inhibition in breast cancer models. We hypothesized that, in HNSCC, targeting BRD4 could overcome cetuximab resistance by depleting alternative RTK expression. We generated independent models of cetuximab resistance in HNSCC cell lines and interrogated their RTK and BRD4 expression profiles. Cetuximab-resistant clones displayed increased expression and activation of several RTK, such as MET and AXL, as well as an increased percentage of BRD4-expressing cells. Both genetic and pharmacologic inhibition of BRD4 abrogated cell viability in models of acquired and intrinsic cetuximab resistance and was associated with a robust decrease in alternative RTK expression by cetuximab. Combined treatment with cetuximab and bromodomain inhibitor JQ1 significantly delayed acquired resistance and RTK upregulation in PDX models of HNSCC. These findings indicate that the combination of cetuximab and bromodomain inhibition may be a promising therapeutic strategy for HNSCC patients.
https://ift.tt/2xazON6
Metabolic and physiologic imaging biomarkers of the tumor microenvironment predict treatment outcome with radiation or a hypoxia-activated prodrug in mice.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by hypoxic niches that lead to treatment resistance. Therefore, studies of tumor oxygenation and metabolic profiling should contribute to improved treatment strategies. Here we define two imaging biomarkers that predict differences in tumor response to therapy: 1) partial oxygen pressure (pO2), measured by EPR imaging; and 2) [1-13C] pyruvate metabolism rate, measured by hyperpolarized 13C MRI. Three human PDAC xenografts with varying treatment sensitivity (Hs766t, MiaPaCa-2, and Su.86.86) were grown in mice. The median pO2 of the mature Hs766t, MiaPaCa-2, and Su.86.86 tumors was 9.1±1.7, 11.1±2.2, and 17.6±2.6 mmHg, and the rate of pyruvate-to-lactate conversion was 2.72±0.48, 2.28±0.26, and 1.98±0.51 min-1, respectively (n=6, each). These results are in agreement with steady state data of matabolites quantified by mass spectroscopy and histological analysis indicating glycolytic and hypoxia profile in Hs766t, MiaPaca-2, and Su.86.86 tumors. Fractionated radiation therapy (5 Gy x 5) resulted in a tumor growth delay of 16.7±1.6 and 18.0±2.7 days in MiaPaca-2 and Su.86.86 tumors, respectively, compared to 6.3±2.7 days in hypoxic Hs766t tumors. Treatment with gemcitabine, a first-line chemotherapeutic agent, or the hypoxia-activated prodrug TH-302 was more effective against Hs766t tumors (20.0±3.5 and 25.0±7.7 days increase in survival time, respectively) than MiaPaCa-2 (2.7±0.4 and 6.7±0.7 days) and Su.86.86 (4.7±0.6 and 0.7±0.6 days) tumors. Collectively, these results demonstrate the ability of molecular imaging biomarkers to predict the response of PDAC to treatment with radiation therapy and TH-302.
https://ift.tt/2kj2Gcw
Isolation‐induced ultrasonic vocalizations in pups: A comparison between Long‐Evans, Sprague–Dawley, and Wistar rats
Developmental Psychobiology, EarlyView.
https://ift.tt/2IIZzVX
Cardiac vagal regulation in infancy predicts executive function and social competence in preschool: Indirect effects through language
Developmental Psychobiology, EarlyView.
https://ift.tt/2IIyXsk
The relation of respiratory sinus arrhythmia to later shyness: Moderation by neighborhood quality
Developmental Psychobiology, EarlyView.
https://ift.tt/2x7EPpr
The development of consistency and flexibility in manual pointing during middle childhood
Developmental Psychobiology, EarlyView.
https://ift.tt/2LnnrQG
Roles of the right temporo‐parietal and premotor cortices in self‐location and body ownership
European Journal of Neuroscience, EarlyView.
https://ift.tt/2koloiV
Case of chondroid syringoma mimicking a nodular hidradenoma: A diagnostic pitfall on cytopathology
Diagnostic Cytopathology, EarlyView.
https://ift.tt/2khZoGy
Atorvastatin and Caffeine in Combination Regulates Apoptosis, Migration, Invasion and Tumorspheres of Prostate Cancer Cells
Abstract
Atorvastatin is the most prescribed cholesterol-lowering statin, while caffeine enhances chemo-sensitivity and induces apoptosis of tumor cells through its DNA repair-inhibiting effect. The present study investigated the effects and mechanisms of atorvastatin and caffeine in combination on human prostate cancer cells cultured in vitro. Cell growth were determined by the trypan blue exclusion assay. The cell apoptosis and colony formation were determined by morphological assessment. The ability of cell migration and invasion were performed using a scratch wound-healing and Transwell assay. Tumorspheres were formed in suspension under the condition of non-adherence and serum-free medium. Finally, the western blot assay was used to determine the levels of proteins. The combination synergistically suppressed proliferation and induced apoptotic death. Meanwhile, the migration, invasion, and the formation of tumorspheres were significantly inhibited by the combination. We found that atorvastatin and caffeine in combination downregulated phospho-Akt, phospho-Erk1/2, anti-apoptotic Bcl-2 and Survivin protein levels. Results of the present study indicate treatment with the combination of caffeine and atorvastatin may be an effective strategy for inhibiting the growth of prostate cancer and should be evaluated clinically.
https://ift.tt/2IZW5BL
ICU Intervention Doesn't Impact Surrogate Psychological Burden
WEDNESDAY, May 23, 2018 -- A family-support intervention delivered by the interprofessional intensive care unit (ICU) team does not significantly impact surrogates' burden of psychological symptoms, according to a study published online May 23 in...
https://ift.tt/2IJjIQ1
12 County-Level Factors Affect Individual Well-Being in U.S.
WEDNESDAY, May 23, 2018 -- Twelve county-level factors, including social and economic, clinical care, and physical environment, explain the majority of variation in resident well-being in the United States, according to a study published online May...
https://ift.tt/2x6NZmf.
E-Cigarette Flavoring Agent May Impair Airway Defense System
WEDNESDAY, May 23, 2018 -- Cinnamaldehyde, a commonly used flavoring agent in electronic cigarettes (e-cigarettes), disrupts mitochondrial function, correlating with impaired cilia beat frequency (CBF), according to a study presented at the American...
https://ift.tt/2ICWgUe
Lung Cancer Incidence Higher for Young Women Than Young Men
WEDNESDAY, May 23, 2018 -- Lung cancer incidence is higher among young women than young men, according to a study published in the May 24 issue of the New England Journal of Medicine. Ahmedin Jemal, D.V.M., Ph.D., from the American Cancer Society in...
https://ift.tt/2IJLB6g
AAP: Congress Urged to Act to Prevent Firearm Deaths
WEDNESDAY, May 23, 2018 -- Pediatricians are joining the call for action to prevent firearm deaths and injuries, according to a letter published by the American Academy of Pediatrics. Following the shooting at Marjory Stoneman Douglas High School in...
https://ift.tt/2IFeO6p
Genomic Variation Among and Within Six Juglans Species
Genomic analysis in Juglans (walnuts) is expected to transform the breeding and agricultural production of both nuts and lumber. To that end, we report here the determination of reference sequences for six additional relatives of Juglans regia: Juglans sigillata (also from section Dioscaryon), Juglans nigra, Juglans microcarpa, Juglans hindsii (from section Rhysocaryon), Juglans cathayensis (from section Cardiocaryon), and the closely related Pterocarya stenoptera. While these are 'draft' genomes, ranging in size between 640Mbp and 990Mbp, their contiguities and accuracies can support powerful annotations of genomic variation that are often the foundation of new avenues of research and breeding. We annotated nucleotide divergence and synteny by creating complete pairwise alignments of each reference genome to the remaining six. In addition, we have re-sequenced a sample of accessions from four Juglans species (including regia). The variation discovered in these surveys comprises a critical resource for experimentation and breeding, as well as a solid complementary annotation. To demonstrate the potential of these resources the structural and sequence variation in and around the polyphenol oxidase loci, PPO1 and PPO2 were investigated. As reported for other seed crops variation in this gene is implicated in the domestication of walnuts. The apparently Juglandaceae specific PPO1 duplicate shows accelerated divergence and an excess of amino acid replacement on the lineage leading to accessions of the domesticated nut crop species, Juglans regia and sigillata.
https://ift.tt/2GKSylJ
Atrioventricular canal defect and genetic syndromes: The unifying role of sonic hedgehog
Clinical Genetics, EarlyView.
https://ift.tt/2J5z2ph
Mutational analysis of CCM1, CCM2 and CCM3 in a Han Chinese cohort with multiple cerebral cavernous malformations in Taiwan
Clinical Genetics, EarlyView.
https://ift.tt/2x6UEgf
Developmental disorders with intellectual disability driven by chromatin dysregulation: Clinical overlaps and molecular mechanisms
Clinical Genetics, EarlyView.
https://ift.tt/2x6z5fQ
Altered dynamics of neurovascular coupling in CADASIL
Annals of Clinical and Translational Neurology, EarlyView.
https://ift.tt/2LpFupx
Serum neurofilament light chain is increased in hereditary spastic paraplegias
Annals of Clinical and Translational Neurology, EarlyView.
https://ift.tt/2x4qomd
Functional high‐intensity training: A HIT to improve insulin sensitivity in type 2 diabetes
Experimental Physiology, EarlyView.
https://ift.tt/2kjAF4B
Physicochemical properties, antioxidant capacities, and metal contents of virgin coconut oil produced by wet and dry processes
Food Science &Nutrition, EarlyView.
https://ift.tt/2s1BlQE
Antiwrinkle and antimelanogenesis activity of the ethanol extracts of Lespedeza cuneata G. Don for development of the cosmeceutical ingredients
Food Science &Nutrition, EarlyView.
https://ift.tt/2KNaZsm
Acetylation of Amaranthus viridis starch: Modeling and process parameters optimization
Food Science &Nutrition, EarlyView.
https://ift.tt/2s40dqU
Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer
Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer
Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer, Published online: 24 May 2018; doi:10.1038/s41416-018-0108-8
Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancerhttps://ift.tt/2x7e9oU
Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams)
Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams)
Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams), Published online: 24 May 2018; doi:10.1038/s41416-018-0107-9
Development and external validation of nomograms in oropharyngeal cancer patients with known HPV-DNA status: a European Multicentre Study (OroGrams)https://ift.tt/2x2lUMO
Impact of race on dose selection of molecular-targeted agents in early-phase oncology trials
Impact of race on dose selection of molecular-targeted agents in early-phase oncology trials
Impact of race on dose selection of molecular-targeted agents in early-phase oncology trials, Published online: 24 May 2018; doi:10.1038/s41416-018-0102-1
Impact of race on dose selection of molecular-targeted agents in early-phase oncology trialshttps://ift.tt/2J5lcDl
The efficacy of VEGFR TKI therapy after progression on immune combination therapy in metastatic renal cell carcinoma
The efficacy of VEGFR TKI therapy after progression on immune combination therapy in metastatic renal cell carcinoma
The efficacy of VEGFR TKI therapy after progression on immune combination therapy in metastatic renal cell carcinoma, Published online: 24 May 2018; doi:10.1038/s41416-018-0104-z
The efficacy of VEGFR TKI therapy after progression on immune combination therapy in metastatic renal cell carcinomahttps://ift.tt/2s7q9RI
Docetaxel enhances lysosomal function through TFEB activation
Docetaxel enhances lysosomal function through TFEB activation
Docetaxel enhances lysosomal function through TFEB activation, Published online: 23 May 2018; doi:10.1038/s41419-018-0571-4
Docetaxel enhances lysosomal function through TFEB activationhttps://ift.tt/2klxc5A
Carnitine palmitoyltransferase gene upregulation by linoleic acid induces CD4+ T cell apoptosis promoting HCC development
Carnitine palmitoyltransferase gene upregulation by linoleic acid induces CD4+ T cell apoptosis promoting HCC development
Carnitine palmitoyltransferase gene upregulation by linoleic acid induces CD4<sup>+</sup> T cell apoptosis promoting HCC development, Published online: 23 May 2018; doi:10.1038/s41419-018-0687-6
Carnitine palmitoyltransferase gene upregulation by linoleic acid induces CD4+ T cell apoptosis promoting HCC developmenthttps://ift.tt/2x6kCjQ
Renal inhibition of miR-181a ameliorates 5-fluorouracil-induced mesangial cell apoptosis and nephrotoxicity
Renal inhibition of miR-181a ameliorates 5-fluorouracil-induced mesangial cell apoptosis and nephrotoxicity
Renal inhibition of miR-181a ameliorates 5-fluorouracil-induced mesangial cell apoptosis and nephrotoxicity, Published online: 23 May 2018; doi:10.1038/s41419-018-0677-8
Renal inhibition of miR-181a ameliorates 5-fluorouracil-induced mesangial cell apoptosis and nephrotoxicityhttps://ift.tt/2J4BxrZ
Inhibition of LCMR1 and ATG12 by demethylation-activated miR-570-3p is involved in the anti-metastasis effects of metformin on human osteosarcoma
Inhibition of LCMR1 and ATG12 by demethylation-activated miR-570-3p is involved in the anti-metastasis effects of metformin on human osteosarcoma
Inhibition of LCMR1 and ATG12 by demethylation-activated miR-570-3p is involved in the anti-metastasis effects of metformin on human osteosarcoma, Published online: 23 May 2018; doi:10.1038/s41419-018-0620-z
Inhibition of LCMR1 and ATG12 by demethylation-activated miR-570-3p is involved in the anti-metastasis effects of metformin on human osteosarcomahttps://ift.tt/2x6kC3k
Nogo-C regulates post myocardial infarction fibrosis through the interaction with ER Ca2+ leakage channel Sec61α in mouse hearts
Nogo-C regulates post myocardial infarction fibrosis through the interaction with ER Ca2+ leakage channel Sec61α in mouse hearts
Nogo-C regulates post myocardial infarction fibrosis through the interaction with ER Ca<sup>2+</sup> leakage channel Sec61α in mouse hearts, Published online: 23 May 2018; doi:10.1038/s41419-018-0598-6
Nogo-C regulates post myocardial infarction fibrosis through the interaction with ER Ca2+ leakage channel Sec61α in mouse heartshttps://ift.tt/2s9GQfj
DNMT1 mediates metabolic reprogramming induced by Epstein–Barr virus latent membrane protein 1 and reversed by grifolin in nasopharyngeal carcinoma
DNMT1 mediates metabolic reprogramming induced by Epstein–Barr virus latent membrane protein 1 and reversed by grifolin in nasopharyngeal carcinoma
DNMT1 mediates metabolic reprogramming induced by Epstein–Barr virus latent membrane protein 1 and reversed by grifolin in nasopharyngeal carcinoma, Published online: 23 May 2018; doi:10.1038/s41419-018-0662-2
DNMT1 mediates metabolic reprogramming induced by Epstein–Barr virus latent membrane protein 1 and reversed by grifolin in nasopharyngeal carcinomahttps://ift.tt/2kiBcnp
Long non-coding RNA H19 contributes to apoptosis of hippocampal neurons by inhibiting let-7b in a rat model of temporal lobe epilepsy
Long non-coding RNA H19 contributes to apoptosis of hippocampal neurons by inhibiting let-7b in a rat model of temporal lobe epilepsy
Long non-coding RNA H19 contributes to apoptosis of hippocampal neurons by inhibiting let-7b in a rat model of temporal lobe epilepsy, Published online: 23 May 2018; doi:10.1038/s41419-018-0496-y
Long non-coding RNA H19 contributes to apoptosis of hippocampal neurons by inhibiting let-7b in a rat model of temporal lobe epilepsyhttps://ift.tt/2s8i1QD
Longevity of bond strength of resin cements to root dentine after radiation therapy
International Endodontic Journal, EarlyView.
https://ift.tt/2LlVitf
Cytokine expression in response to root repair agents
International Endodontic Journal, EarlyView.
https://ift.tt/2IGXycP
Prevotella strains and lactamic resistance gene distribution in different oral environments of children with pulp necrosis
International Endodontic Journal, EarlyView.
https://ift.tt/2IEUKky
Ten‐year follow‐up of dental implants used for immediate loading in the edentulous mandible: A prospective clinical study
Clinical Implant Dentistry and Related Research, EarlyView.
https://ift.tt/2GK4Omo
Effect of implant therapy on oral health‐related quality of life (OHIP‐49), health status (SF‐36), and satisfaction of patients with several agenetic teeth: Prospective cohort study
Clinical Implant Dentistry and Related Research, EarlyView.
https://ift.tt/2IKH47S
Peri‐implant soft tissue status and crestal bone levels around adjacent implants placed in patients with and without type‐2 diabetes mellitus: 6 years follow‐up results
Clinical Implant Dentistry and Related Research, EarlyView.
https://ift.tt/2s8HIk8
Unusual presentation of calcific tendinitis of the iliopsoas tendon in a 28‐year‐old female
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2klVtIY
Pyelo‐choledochal fistulation on intraoperative cholangiogram
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2IFZdn3
Mobility scores as a predictor of length of stay in general surgery: a prospective cohort study
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2GJ64qd
Identification of Hub Genes and Key Pathways Associated with Two Subtypes of Diffuse Large B-Cell Lymphoma Based on Gene Expression Profiling via Integrated Bioinformatics
There is a significant difference in prognosis between the germinal center B-cell (GCB) and activated B-cell (ABC) subtypes of diffuse large B-cell lymphoma (DLBCL). However, the signaling pathways and driver genes involved in these disparate subtypes are ambiguous. This study integrated three cohort profile datasets, including 250 GCB samples and 250 ABC samples, to elucidate potential candidate hub genes and key pathways involved in these two subtypes. Differentially expressed genes (DEGs) were identified. After Gene Ontology functional enrichment analysis of the DEGs, protein-protein interaction (PPI) network and sub-PPI network analyses were conducted using the STRING database and Cytoscape software. Subsequently, the Oncomine database and the cBioportal online tool were employed to verify the alterations and differential expression of the 8 hub genes (MME, CD44, IRF4, STAT3, IL2RA, ETV6, CCND2, and CFLAR). Gene set enrichment analysis was also employed to identify the intersection of the key pathways (JAK-STAT, FOXO, and NF-κB pathways) validated in the above analyses. These hub genes and key pathways could improve our understanding of the process of tumorigenesis and the underlying molecular events and may be therapeutic targets for the precise treatment of these two subtypes with different prognoses.
https://ift.tt/2J2Ftt5
The Use of Phage Display and Yeast Based Expression System for the Development of a Von Willebrand Factor Propeptide Assay: Development of a Von Willebrand Factor Propeptide Assay
Background. The diagnosis of von Willebrand disease is complex due to the heterogeneity of the disease. About eighty percent of von Willebrand disease patients are diagnosed with a quantitative defect of von Willebrand factor (VWF) where fifty percent is due to an increased clearance of von Willebrand factor. These patients do not respond well to the treatment of choice, Desmopressin (DDAVP) due to decreased efficacy. The ratio between the VWF propeptide and the mature VWF antigen is used to diagnose these patients. Commercial VWF propeptide assays are too expensive for use in developing countries. In this study, we developed a cost-effective ELISA assay. Methods. We first displayed VWF propeptide on yeast. Antibody fragments were selected against the displayed VWF propeptide by using phage display technology. The antibodies were used to develop a cost-effective VWF propeptide assay and compared to a commercial VWF propeptide assay. Results. Two of these antibody fragments bound specific to the VWF propeptide and not to the yeast used for the expression of the propeptides. These purified antibody fragments were able to detect VWF propeptide in normal plasma. Conclusion. Our assay performed well when compared to a commercial kit. It also showed a higher binding affinity for VWF propeptide in plasma at especially lower plasma concentrations.
https://ift.tt/2kiis7I
Krüppel‐like factor 4 promotes c‐Met amplification‐mediated gefitinib resistance in non‐small‐cell lung cancer
Cancer Science, EarlyView.
https://ift.tt/2xgXwYb
Endoplasmic reticulum stress‐mediated autophagy protects against β,β‐dimethylacrylshikonin‐induced apoptosis in lung adenocarcinoma cells
Cancer Science, EarlyView.
https://ift.tt/2LnfScK
Prognostic value of nutritional risk screening 2002 scale in nasopharyngeal carcinoma: A large‐scale cohort study
Cancer Science, EarlyView.
https://ift.tt/2xgXvU7
PRMT9 promotes hepatocellular carcinoma invasion and metastasis via activating PI3K/Akt/GSK‐3β/Snail signaling
Cancer Science, Volume 109, Issue 5, Page 1414-1427, May 2018.
https://ift.tt/2IGzz1G
Issue Information
Cancer Science, Volume 109, Issue 5, Page 1277-1279, May 2018.
https://ift.tt/2IJT70Q
LKB1 obliterates Snail stability and inhibits pancreatic cancer metastasis in response to metformin treatment
Cancer Science, Volume 109, Issue 5, Page 1382-1392, May 2018.
https://ift.tt/2LqBUvt
Current state of therapeutic development for rare cancers in Japan, and proposals for improvement
Cancer Science, Volume 109, Issue 5, Page 1731-1737, May 2018.
https://ift.tt/2IJWwgi
Podoplanin: An emerging cancer biomarker and therapeutic target
Cancer Science, Volume 109, Issue 5, Page 1292-1299, May 2018.
https://ift.tt/2LpAdhQ
Influence of different drilling preparation on cortical bone: A biomechanical, histological, and micro‐CT study on sheep
Clinical Oral Implants Research, EarlyView.
https://ift.tt/2GLPqWC
Cover
Clinical Oral Implants Research, Volume 29, Issue 5, Page i-i, May 2018.
https://ift.tt/2J0PozE
What is the effect of secondary (high) schooling on subsequent medical school performance? A national, UK-based, cohort study
Objectives
University academic achievement may be inversely related to the performance of the secondary (high) school an entrant attended. Indeed, some medical schools already offer 'grade discounts' to applicants from less well-performing schools. However, evidence to guide such policies is lacking. In this study, we analyse a national dataset in order to understand the relationship between the two main predictors of medical school admission in the UK (prior educational attainment (PEA) and performance on the United Kingdom Clinical Aptitude Test (UKCAT)) and subsequent undergraduate knowledge and skills-related outcomes analysed separately.
MethodsThe study was based on national selection data and linked medical school outcomes for knowledge and skills-based tests during the first five years of medical school. UKCAT scores and PEA grades were available for 2107 students enrolled at 18 medical schools. Models were developed to investigate the potential mediating role played by a student's previous secondary school's performance. Multilevel models were created to explore the influence of students' secondary schools on undergraduate achievement in medical school.
ResultsThe ability of the UKCAT scores to predict undergraduate academic performance was significantly mediated by PEA in all five years of medical school. Undergraduate achievement was inversely related to secondary school-level performance. This effect waned over time and was less marked for skills, compared with undergraduate knowledge-based outcomes. Thus, the predictive value of secondary school grades was generally dependent on the secondary school in which they were obtained.
ConclusionsThe UKCAT scores added some value, above and beyond secondary school achievement, in predicting undergraduate performance, especially in the later years of study. Importantly, the findings suggest that the academic entry criteria should be relaxed for candidates applying from the least well performing secondary schools. In the UK, this would translate into a decrease of approximately one to two A-level grades.
https://ift.tt/2KN2ZaO
Reducing Bacterial Infections and Biofilm Formation Using Nanoparticles and Nanostructured Antibacterial Surfaces
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2LrFkxU
Bone Regeneration: Novel 3D Hybrid Nanofiber Aerogels Coupled with BMP‐2 Peptides for Cranial Bone Regeneration (Adv. Healthcare Mater. 10/2018)
Advanced Healthcare Materials, Volume 7, Issue 10, May 23, 2018.
https://ift.tt/2GLXUNx
Loss of cyclin‐dependent kinase‐like 2 predicts poor prognosis in gastric cancer, and its overexpression suppresses cells growth and invasion
Cancer Medicine, EarlyView.
https://ift.tt/2x9sKQK
Genetically determined height was associated with lung cancer risk in East Asian population
Cancer Medicine, EarlyView.
https://ift.tt/2J21j04
Rolapitant for the prevention of nausea in patients receiving highly or moderately emetogenic chemotherapy
Cancer Medicine, EarlyView.
https://ift.tt/2x90hdX
Gemcitabine and cisplatin regimen facilitates prognosis of advanced nasopharyngeal carcinoma
Cancer Medicine, EarlyView.
https://ift.tt/2kkq2OX
The effects of aberrant expression of LncRNA DGCR5/miR‐873‐5p/TUSC3 in lung cancer cell progression
Cancer Medicine, EarlyView.
https://ift.tt/2kjwXYP
A distinctively expressed long noncoding RNA, RP11‐466I1.1, may serve as a prognostic biomarker in hepatocellular carcinoma
Cancer Medicine, EarlyView.
https://ift.tt/2xdgZZM
Long noncoding RNA UFC1 is activated by E2F1 and exerts oncogenic properties by functioning as a ceRNA of FOXP3
Cancer Medicine, EarlyView.
https://ift.tt/2J5stD9
Prognostic significance of combined pretreatment lymphocyte counts and body mass index in patients with head and neck cancer treated with radiation therapy
Cancer Medicine, EarlyView.
https://ift.tt/2s9pmzo
Glioblastoma recurrence correlates with NLGN3 levels
Cancer Medicine, EarlyView.
https://ift.tt/2x5MHrN
LGR5 promotes epithelial ovarian cancer proliferation, metastasis, and epithelial–mesenchymal transition through the Notch1 signaling pathway
Cancer Medicine, EarlyView.
https://ift.tt/2J0tZGJ
Annual Report to the Nation on the Status of Cancer, part II: Recent changes in prostate cancer trends and disease characteristics
Cancer, EarlyView.
https://ift.tt/2IZKR05
Annual Report to the Nation on the Status of Cancer, part I: National cancer statistics
Cancer, EarlyView.
https://ift.tt/2x9T9Oo
The pendulum swings back: Screening for prostate cancer in 2018
Cancer, EarlyView.
https://ift.tt/2klqA7g
PSA screening, prostate biopsy, and treatment of prostate cancer in the years surrounding the USPSTF recommendation against prostate cancer screening
Cancer, EarlyView.
https://ift.tt/2x6UTYR
Liquid biopsies offer promise and challenges
Cancer, Volume 124, Issue 11, Page 2269-2270, June 1, 2018.
https://ift.tt/2s4a3YM
Issue Information
Cancer, Volume 124, Issue 11, Page 2259-2268, June 1, 2018.
https://ift.tt/2IZCGAX
More evidence that gum disease increases cancer risk
Cancer, Volume 124, Issue 11, Page 2270-2271, June 1, 2018.
https://ift.tt/2x69Nye
Recurrent GNA14 mutations in anastomosing haemangiomas
Histopathology, EarlyView.
https://ift.tt/2IL2cXr
Low‐grade intraductal carcinoma of the salivary gland with prominent oncocytic change: a newly described variant
Histopathology, EarlyView.
https://ift.tt/2rZ5ShV
The value of grading dysplasia in appendiceal mucinous neoplasm in the absence of pseudomyxoma peritonei
Histopathology, EarlyView.
https://ift.tt/2IGPvwD
Validation of the systematic scoring of immunohistochemically stained tumour tissue microarrays using QuPath digital image analysis
Histopathology, EarlyView.
https://ift.tt/2rZ5boP
Issue Information
Academic Emergency Medicine, Volume 25, Issue 5, Page 477-481, May 2018.
https://ift.tt/2KOTs3f
Spatial Semantics, Cognition, and Their Interaction: A Comparative Study of Spatial Categorization in English and Korean
Cognitive Science, EarlyView.
https://ift.tt/2IGlOQB
Lexical Learning May Contribute to Phonetic Learning in Infants: A Corpus Analysis of Maternal Spanish
Cognitive Science, EarlyView.
https://ift.tt/2IIHYxz
Improved Stable Indocyanine Green (ICG)‐Mediated Cancer Optotheranostics with Naturalized Hepatitis B Core Particles
Advanced Materials, EarlyView.
https://ift.tt/2LpksqU
Gap‐Mode Surface‐Plasmon‐Enhanced Photoluminescence and Photoresponse of MoS2
Advanced Materials, EarlyView.
https://ift.tt/2IJi1hp
Injectable Bioresponsive Gel Depot for Enhanced Immune Checkpoint Blockade
Advanced Materials, EarlyView.
https://ift.tt/2IHhhNM
A Novel Conductive Mesoporous Layer with a Dynamic Two‐Step Deposition Strategy Boosts Efficiency of Perovskite Solar Cells to 20%
Advanced Materials, EarlyView.
https://ift.tt/2IJhYCf
Perovskite Solar Cells with Inorganic Electron‐ and Hole‐Transport Layers Exhibiting Long‐Term (≈500 h) Stability at 85 °C under Continuous 1 Sun Illumination in Ambient Air
Advanced Materials, EarlyView.
https://ift.tt/2IFsYEC
Automated Buildup of Biomimetic Films in Cell Culture Microplates for High‐Throughput Screening of Cellular Behaviors
Advanced Materials, EarlyView.
https://ift.tt/2IJhX19
Piezoelectric Nanogenerators: Point‐Defect‐Passivated MoS2 Nanosheet‐Based High Performance Piezoelectric Nanogenerator (Adv. Mater. 21/2018)
Advanced Materials, Volume 30, Issue 21, May 24, 2018.
https://ift.tt/2LrKrOG
Flexoelectricity in Bones
Advanced Materials, Volume 30, Issue 21, May 24, 2018.
https://ift.tt/2IJkAQv
Configurable Integrations: Configurable Integration of On‐Chip Quantum Dot Lasers and Subwavelength Plasmonic Waveguides (Adv. Mater. 21/2018)
Advanced Materials, Volume 30, Issue 21, May 24, 2018.
https://ift.tt/2LqStaf
Biomaterials: Synthetic Biology Makes Polymer Materials Count (Adv. Mater. 21/2018)
Advanced Materials, Volume 30, Issue 21, May 24, 2018.
https://ift.tt/2x6qrxU
Lithium‐Metal Batteries: High‐Voltage Lithium‐Metal Batteries Enabled by Localized High‐Concentration Electrolytes (Adv. Mater. 21/2018)
Advanced Materials, Volume 30, Issue 21, May 24, 2018.
https://ift.tt/2LqRLdq
Neuromorphic Computing: Ion Gated Synaptic Transistors Based on 2D van der Waals Crystals with Tunable Diffusive Dynamics (Adv. Mater. 21/2018)
Advanced Materials, Volume 30, Issue 21, May 24, 2018.
https://ift.tt/2IJkuZd
Masthead: (Adv. Mater. 21/2018)
Advanced Materials, Volume 30, Issue 21, May 24, 2018.
https://ift.tt/2IIyRRm
Quantum Dots: Site‐Controlled Single‐Photon Emitters Fabricated by Near‐Field Illumination (Adv. Mater. 21/2018)
Advanced Materials, Volume 30, Issue 21, May 24, 2018.
https://ift.tt/2IIHrM5
Contents: (Adv. Mater. 21/2018)
Advanced Materials, Volume 30, Issue 21, May 24, 2018.
https://ift.tt/2IEZ2IB
Enhanced Performance of a Molecular Photoacoustic Imaging Agent by Encapsulation in Mesoporous Silicon Nanoparticles
Advanced Materials, EarlyView.
https://ift.tt/2x2u7AC
Hospital readmissions, mortality and potentially inappropriate prescribing: a retrospective study of older adults discharged from hospital
British Journal of Clinical Pharmacology, EarlyView.
https://ift.tt/2LrC45E
Population pharmacokinetics of tacrolimus in children with nephrotic syndrome
British Journal of Clinical Pharmacology, EarlyView.
https://ift.tt/2GLqYVv
Evaluation of sex‐by‐formulation interaction in bioequivalence studies of efavirenz tablets
British Journal of Clinical Pharmacology, EarlyView.
https://ift.tt/2LoCGcl
Pharmacokinetics of efavirenz in patients on antituberculosis treatment in high human immunodeficiency virus and tuberculosis burden countries: A systematic review
British Journal of Clinical Pharmacology, EarlyView.
https://ift.tt/2KOEeeh
Anti‐inflammatory potency testing of topical corticosteroids and calcineurin inhibitors in human volunteers sensitized to diphenylcyclopropenone
British Journal of Clinical Pharmacology, EarlyView.
https://ift.tt/2Lrrziz
Laparoscopic radical nephrectomy for a right renal tumor with renal vein tumor thrombus in a patient with situs inversus totalis
Asian Journal of Endoscopic Surgery, EarlyView.
https://ift.tt/2GLqMWh
Inguinoscrotal hernia containing the urinary bladder successfully repaired using laparoscopic transabdominal preperitoneal repair technique: A case report
Asian Journal of Endoscopic Surgery, EarlyView.
https://ift.tt/2J8aufc
Combination of endoscopic submucosal dissection and transanal minimally invasive surgery for the resection of early rectal cancer with fibrosis after prior partial excision
Asian Journal of Endoscopic Surgery, EarlyView.
https://ift.tt/2GKKzVM
Commentary on “The impact of nonadherence to antiseizure drugs on seizure outcomes in an animal model of epilepsy”
Epilepsia, EarlyView.
https://ift.tt/2IFLCrQ
Evolution of lobar abnormalities of cerebral glucose metabolism in 41 children with drug‐resistant epilepsy
Epilepsia, EarlyView.
https://ift.tt/2s3OGYJ
The novel sodium channel modulator GS‐458967 (GS967) is an effective treatment in a mouse model of SCN8A encephalopathy
Epilepsia, EarlyView.
https://ift.tt/2IGOg0r
An interview with Kyle Thomson, 2018 Epilepsia Prize Winner for Basic Science Research
Epilepsia, EarlyView.
https://ift.tt/2s3R55C
Hepatocyte microvesicle levels improve prediction of mortality in patients with cirrhosis
Hepatology, EarlyView.
https://ift.tt/2IZzG7F
PRDM8 exhibits antitumor activities toward hepatocellular carcinoma by targeting NAP1L1
Hepatology, EarlyView.
https://ift.tt/2KODu8Z
The high burden of alcoholic cirrhosis in privately insured persons in the United States
Hepatology, EarlyView.
https://ift.tt/2Lo5GRi
Loss of PDK4 switches the hepatic NF‐κB/TNF pathway from pro‐survival to pro‐apoptosis
Hepatology, EarlyView.
https://ift.tt/2KMVzo6
Receipt of a pediatric liver offer as the first offer reduces waitlist mortality for adult women
Hepatology, EarlyView.
https://ift.tt/2IZzFAD
Link between gut‐microbiome derived metabolite and shared gene‐effects with hepatic steatosis and fibrosis in NAFLD
Hepatology, EarlyView.
https://ift.tt/2KMVsZI
Hepatology Highlights
Hepatology, Volume 67, Issue 6, Page 2065-2067, June 2018.
https://ift.tt/2Lkp1Tz
Instructions to authors and Information for readers
Hepatology, Volume 67, Issue 6, June 2018.
https://ift.tt/2KMV6SS
Hepatic CREBZF couples insulin to lipogenesis by inhibiting insig activity and contributes to hepatic steatosis in diet‐induced insulin‐resistant mice
Hepatology, EarlyView.
https://ift.tt/2J6ldqR
The diagnostic role of BAP1 in serous effusions
The aim of this study was to analyze the diagnostic role of BAP1 in effusion cytology. Effusions (n=258), consisting of 53 malignant mesotheliomas and 205 other cancers, the majority carcinomas (62 breast, 60 ovarian, 31 lung, 51 carcinomas of other origin, 1 melanoma), were analyzed for BAP1 expression using immunohistochemistry. BAP1 was lost in 46 (87%) mesotheliomas, compared to 4/205 (2%) loss in other cancers (P<.001), resulting in sensitivity and specificity of 87% and 98%, respectively. There was no significant difference between peritoneal (n=14) and pleural (n=39) mesotheliomas.
https://ift.tt/2Ls1bFl
Impacts of supplementing growing rabbit diets with whey powder and citric acid on growth performance, nutrient digestibility, meat and bone analysis, and gut health
The present study evaluated the impact of supplementing the rabbit diet with graded levels of whey powder and citric acid. The dietary treatments were as follows: T1, control diet (basal diet); T2, basal diet ...
https://ift.tt/2LkmJUt
Relative Adrenal Insufficiency in Cirrhotic Patients with Ascites (Hepatoadrenal Syndrome)
Relative adrenal insufficiency (RAI) has been reported in critically ill patients with cirrhosis. We evaluated the prevalence of RAI and its relationship to clinical course in non-septic cirrhosis patients with ascites.
https://ift.tt/2s739SV
Crestline to deliver $4.5 million in specialized ambulances to the Department of National Defence
Saskatoon, SK, Canada — Crestline Coach, a global leader in ambulance and specialty vehicle manufacturing and a Canadian supplier of small to mid-sized buses, secured a contract with the Department of National Defence to manufacture specialized ambulances for Canadian Armed Forces military bases, situated coast to coast. The contract is valued at $4.5 million, excluding options. With its rugged ...
https://ift.tt/2J7XINM
Food Protein–Induced Enterocolitis Instead of Necrotizing Enterocolitis? A Neonatal Intensive Care Unit Case Series
Necrotizing enterocolitis is an important disease in infants born premature. However, other disease entities present with similar signs and symptoms. This series reviews 5 atypical cases initially diagnosed as necrotizing enterocolitis that may be more consistent with food protein–induced enterocolitis. Food protein–induced enterocolitis may be underdiagnosed in this population.
https://ift.tt/2IGc5ty
Association between Clustering of Lifestyle Behaviors and Health-Related Physical Fitness in Youth: The UP&DOWN Study
To examine clustering of lifestyle behaviors in Spanish children and adolescents based on screen time, nonscreen sedentary time, moderate-to-vigorous physical activity, Mediterranean diet quality, and sleep time, and to analyze its association with health-related physical fitness.
https://ift.tt/2LqPbE8
The Oro-Helical Length Accurately Predicts Endotracheal Tube Insertion Depth in Neonates
We evaluated the reliability of the oro-helical length in predicting the ideal endotracheal tube depth in neonates and found the oro-helical length was a consistently more reliable and better predictor of the ideal endotracheal tube depth on chest radiograph than the 7-8-9 rule, especially in infants weighing ≤1500 g.
https://ift.tt/2IFvKpg
Cardiopulmonary Adaptation During First Day of Life in Human Neonates
To characterize the natural history of cardiopulmonary physiology in the first 24 hours after birth.
https://ift.tt/2x67GdY
Implementation of a Population-Based Cirrhosis Identification and Management System
Cirrhosis-related morbidity and mortality is potentially preventable. Antiviral treatment in patients with cirrhosis-related to hepatitis C virus (HCV) or hepatitis B virus can prevent complications.1–3 Beta-blockers and endoscopic treatments of esophageal varices are effective in primary prophylaxis of variceal hemorrhage.4 Surveillance for hepatocellular cancer is associated with increased detection of early stage cancer and improved survival.5 However, many patients with cirrhosis are either not diagnosed in a primary care setting, or even when diagnosed, not seen or referred to specialty clinics to receive disease-specific care,6 and thus remain at high risk for complications.
https://ift.tt/2x7hyUH
Interrelationship Between Fractal Ornament and Multilevel Selection Theory
Abstract
Interdisciplinarity is one of the features of modern science, defined as blurring the boundaries of disciplines and overcoming their limitations or excessive specialization by borrowing methods from one discipline into another, integrating different theoretical assumptions, and using the same concepts and terms. Often, theoretical knowledge of one discipline and technological advances of another are combined within an interdisciplinary science, and new branches or disciplines may also emerge. Biosemiotics, a field that arose at the crossroads of biology, semiotics, linguistics, and philosophy, enables scientists to borrow theoretical assumptions from semiotics and extend them to different biological theories. The latter applies especially to extended synthesis, wherein culture is viewed as one of the factors influencing evolution. In the present research, the semiotic system of Ukrainian folk ornament is analyzed through the theory of fractals, key features of which are recursion and self-similarity. As a result, an assumption is made about the fractal structure of culture and social life on a conceptual level. What follows is a discussion of how this assumption can contribute to the multilevel selection theory, one of the foundations of extended synthesis, which employs the concept of self-similarity at all levels of the biological hierarchy.
https://ift.tt/2IGaDD7
Semiotic Mechanisms Underlying Niche Construction
Abstract
The explanatory value of niche construction can be strengthened by firm footing in semiotic theory. Anthropologists have a unique perspective on the integration of such diverse approaches to human action and evolutionary processes. Here, we seek to open a dialogue between anthropology and biosemiotics. The overarching aim of this paper is to demonstrate that niche construction, including the underlying mechanism of reciprocal causation, is a semiotic process relating to biological development (sensu stricto) as well as cognitive development and cultural change. In making this argument we emphasize the semiotic mechanisms underlying the niche concept. We argue that the "niche" in ecology and evolutionary biology can be consistent with the Umwelt of Jakob von Uexkull. Following John Deely we therefore suggest that investigations into the organism—environment interface constituting niche construction should emphasize the semiotic basis of experience. Peircean signs are pervasive and allow for flexible interpretations of phenomena in relation to the perceptual and cognitive capacities of the behaving organism, which is particularly pertinent for understanding the relation of proximate/ultimate selective forces as co-productive (i.e., reciprocal). Additionally, theoretical work by Kinji Imanishi on the evolution of daily life and Gregory Bateson's relational view of evolution both support the linkage between proximate and ultimate evolutionary processes of causation necessitated by the niche construction perspective. We will then apply this theoretical framework to two specific examples: 1) hominin evolution, including uniquely human cultural behaviors with niche constructive implications; and 2) the multispecies and anthropocentric niche of human-dog coevolution from which complex cognitive capacities and semiotic relationships emerged. The intended outcome of this paper is the establishment of concrete semiotic mechanisms and theory underlying niche constructive behavior which can then be applied to a broad spectrum of organisms to contextualize the reciprocal relation between proximate and ultimate drivers of behavior.
https://ift.tt/2IED2xv
Biosemiotics, the Extended Synthesis, and Ecological Information: Making Sense of the Organism-Environment Relation at the Cognitive Level
Abstract
This paper argues that the Extended Synthesis, ecological information, and biosemiotics are complementary approaches whose engagement will help us explain the organism-environment interaction at the cognitive level. The Extended Synthesis, through niche construction theory, can explain the organism-environment interaction at an evolutionary level because niche construction is a process guided by information. We believe that the best account that defines information at this level is the one offered by biosemiotics and, within all kinds of biosemiotic information available, we believe that ecological information (information for affordances) is the best candidate for making sense of the organism-environment relation at the cognitive level. This entanglement of biosemiotics, ecological information and the Extended Synthesis is promising for understanding the multidimensional character of the organism-environment reciprocity as well as the relation between evolution, cognition, and meaning.
https://ift.tt/2x8aUgT
Automated chest screening based on a hybrid model of transfer learning and convolutional sparse denoising autoencoder
In this paper, we aim to investigate the effect of computer-aided triage system, which is implemented for the health checkup of lung lesions involving tens of thousands of chest X-rays (CXRs) that are required...
https://ift.tt/2IFWz0D
A Randomized Trial of a Family-Support Intervention in Intensive Care Units
Approximately one in five persons in the United States dies in or shortly after discharge from an intensive care unit (ICU), typically after a decision has been made by the patient's surrogate decision maker to forgo life-prolonging therapies. Problems with communication between clinicians and…
https://ift.tt/2GHw3y8
Antimicrobial susceptibility of Campylobacter jejuni and Campylobacter coli: comparison between Etest and a broth dilution method
Campylobacter is a leading cause of foodborne gasteroenteritis worldwide. Antimicrobial susceptibility testing for Campylobacter spp. is not routinely performed by most clinical laboratories. However, the emergen...
https://ift.tt/2s1IMam
When will every EMT wear a body camera?
An EMT's attack of a restrained patient is a reminder for all leaders to discuss response to provocations and consider body-worn cameras to capture the EMS point-of-view
https://ift.tt/2s8GZ2i
An Ultrahigh-throughput Microfluidic Platform for Single-cell Genome Sequencing
https://ift.tt/2GKdPvH
Dynamics of colistin and tobramycin resistance among Enterobacter cloacae during prolonged use of selective decontamination of the digestive tract
A high prevalence of colistin resistance among E. cloacae isolates in two intensive care units (ICU) (of 16 and 6 beds) using selective digestive decontamination (SDD) since 1990 instigated a retrospective and pr...
https://ift.tt/2kiOyA7
Comparison of aqueous, polyethylene glycol-aqueous and ethanolic propolis extracts: antioxidant and mitochondria modulating properties
Propolis is multicomponent substance collected by honeybees from various plants. It is known for numerous biological effects and is commonly used as ethanolic extract because most of active substances of propo...
https://ift.tt/2s4k6xO
Hopkins syndrome following the first episode of bronchial asthma associated with enterovirus D68: a case report
Hopkins syndrome (HS) is a rare disorder presenting with acute flaccid paralysis of the limbs following an asthma attack. Neurologists encounter a diagnostic challenge if patients without a history of bronchia...
https://ift.tt/2IFlY6y
Anti-ganglioside complex antibody profiles in a recurrent complicated case of GQ1b-seronegative miller fisher syndrome and Bickerstaff brainstem encephalitis: a case report
Guillain-Barré syndrome (GBS), Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE) are a group of autoimmune neurological disorders (GBS spectrum disorder) that rarely recur. Recently, an...
https://ift.tt/2s393Fj
Longevity and pleural mesothelioma: age-period-cohort analysis of incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program, 1973–2013
This study investigates the hypothesis that an increasing fraction of incident pleural mesothelioma (PM) in the US population may be related to longevity, i.e., to expansion of the population over age 75 years...
https://ift.tt/2ILFY7O
Ketamine and electroconvulsive therapy: so happy together?
Purpose of review Anesthetics, such as thiopental, methohexital, propofol and ketamine have been used to induce unconsciousness for electroconvulsive therapy (ECT), each with its advantages and disadvantages. Only until recently was it discovered that ketamine may have inherent antidepressant effects. We reviewed the side effect profile of ketamine and examined the literature for whether or not ketamine augments the antidepressant effects of ECT. Recent findings Systematic reviews and meta-analyses of randomized controlled trials of the potential benefits of adding ketamine to ECT treatment have generated varied conclusions. Currently there is a lack of clear evidence that ketamine with ECT is more efficacious than ECT alone. Summary Large, multicenter randomized controlled trials are needed to further investigate the potential advantages of adding ketamine to ECT for patients with severe or refractory depression. The addition of ketamine to ECT treatment may have some early beneficial effect in patients with acute depressive disorders. Most likely, ECT itself is responsible for lasting remission from severe depression. Ketamine's side effect profile may be undesirable in certain patient populations, and so the risks and benefits of the addition of this drug to ECT treatment must be weighed. Correspondence to Kathryn Cobb, MD, N2198 UNC Hospitals, CB# 7010, Chapel Hill, NC 27599-7010, USA. Tel: +1 919 966 5136; e-mail: kathryn_cobb@med.unc.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2kl4nGA
https://ift.tt/2kl4nGA
Recommendations Developed for Managing Postpartum Pain
WEDNESDAY, May 23, 2018 -- Recommendations for managing postpartum pain have been developed and published in a Committee Opinion online May 17 in Obstetrics & Gynecology. Tekoa L. King, M.P.H., from the American College of Nurse-Midwives in...
https://ift.tt/2ko2JEh
Less Driving Tied to Lower Cardiovascular Disease Risk
WEDNESDAY, May 23, 2018 -- More active alternatives to the car for travel are associated with a reduced risk of cardiovascular disease (CVD) and all-cause mortality, according to a study published online May 21 in Heart. Jenna Panter, Ph.D., from...
https://ift.tt/2s5p4ty
Cryoablation Efficacious for Cancer Pain, Review Finds
WEDNESDAY, May 23, 2018 -- Cryoablation is effective for controlling cancer pain without many side effects, according to a review published online May 7 in PAIN Practice. Laura Ferrer-Mileo, from L'Hospitalet de Llobregat in Barcelona, Spain, and...
https://ift.tt/2IEFwvX
Better Social Support Network Protects Black Men Against HIV
WEDNESDAY, May 23, 2018 -- A better social support network may help protect black men who have sex with men (BMSM) against HIV acquisition, according to a study published in the June issue of the Journal of Acquired Immune Deficiency Syndrome. Keith...
https://ift.tt/2GIVQpM
Pediatricians Should Advocate for Life Support Training
WEDNESDAY, May 23, 2018 -- Pediatricians should advocate for life support training for children, parents, caregivers, school personnel, and the public, according to a technical report and policy statement published online May 23 in Pediatrics. Susan...
https://ift.tt/2IK4jPq
Morbidity in Pregnancy Common for Women With Heart Disease
WEDNESDAY, May 23, 2018 -- For women with heart disease, cardiac complications occur in 16 percent of pregnancies and are mainly linked to arrhythmias and heart failure, according to a study published in the May 29 issue of the Journal of the...
https://ift.tt/2GKyXC8
Dupilumab Reduces Rate of Severe Asthma Exacerbations
WEDNESDAY, May 23, 2018 -- Add-on dupilumab reduces the rate of severe asthma exacerbations in uncontrolled asthma; it also reduces the glucocorticoid dose for glucocorticoid-treated asthma, according to two studies published online May 21 in the...
https://ift.tt/2khIHv0
Vitamin D Supplement Tied to Less Wheezing in Black Preemies
WEDNESDAY, May 23, 2018 -- Vitamin D sustained supplementation is associated with reduced recurrent wheezing among black infants born preterm, according to a study published in the May 22/29 issue of the Journal of the American Medical...
https://ift.tt/2s8NfXQ
Extended INR Test Intervals Safe for Warfarin-Treated Patients
WEDNESDAY, May 23, 2018 -- For stable warfarin-treated patients, extended international normalized ratio (INR) testing can be successfully and safely implemented, according to a study published online May 15 in the Journal of Thrombosis and...
https://ift.tt/2kl4h1G
Inverse Link for Plasma 25(OH)D Concentration, Risk of T2DM
WEDNESDAY, May 23, 2018 -- There is an inverse association for plasma 25-hydroxyvitamin D (25[OH]D) concentration with diabetes risk, according to a study published online April 19 in PLOS ONE. Sue K. Park, M.D., Ph.D., from the Seoul National...
https://ift.tt/2s6AL33
Cannula Implantation into the Cisterna Magna of Rodents
Here we describe a protocol to perform cisterna magna cannulation (CMc), a minimally invasive way to deliver tracers, substrates and signaling molecules into the cerebrospinal fluid (CSF). Combined with different imaging modalities, CMc enables glymphatic system and CSF dynamics assessment, as well as brain-wide delivery of various compounds.
https://ift.tt/2J0nT9o
NERVE STIMULATION ENHANCES TASK-ORIENTED TRAINING FOR MODERATE-TO-SEVERE HEMIPARESIS 3-12 MONTHS AFTER STROKE: A RANDOMIZED TRIAL
Objective Determine whether somatosensory stimulation affects outcomes of motor training for moderate-to-severe upper extremity hemiparesis less than 12 months post-stroke. Design 55 adults participated in 18 intervention sessions pairing 2 hours of active (n=33) or sham (n=22) somatosensory stimulation with 4 hours of intensive task-oriented motor training. Wolf Motor Function Test, Action Research Arm Test, Fugl-Meyer Assessment, and Stroke Impact Scale were administered at baseline, post-intervention, and 1- and 4-month follow-up. Results Statistically significant between-groups differences favored the active condition on Wolf Motor Function Test at post (p=0.04) and Action Research Arm Test at post (p=0.02), 1-month (p=0.01), and 4-month (p=0.01) but favored the sham condition on Stroke Impact Scale at 1-month (p=0.03). There were no significant between-groups differences on Fugl-Meyer Assessment. Conclusion Somatosensory stimulation can improve objective outcomes of motor training for moderate-to-severe hemiparesis less than 12 months after stroke, although the magnitude of between-groups differences in this study needs to be determined if they are clinically relevant. Future studies should investigate the intervention's impact on disability and functional recovery for this population as well as neurophysiological mechanisms underlying intervention effects. Corresponding author: Lumy Sawaki, MD, PhD, University of Kentucky Department of Physical Medicine and Rehabilitation at Cardinal Hill Hospital, 2050 Versailles Road, Lexington, KY 40504 (lsawa2@uky.edu; phone 859/323-6226; fax 859/323-1123) Disclosures: This study was funded by the National Institutes of Health R01 NIH HD056002, ARRA Administrative Supplement, and the Cardinal Hill Rehabilitation Hospital Endowed Chair in Stroke and Spinal Cord Injury Rehabilitation (0705129700). There are no financial benefits to the authors. Results of this study were first presented in poster form at the 2015 Conference of the American Society of Neurorehabilitation. There are no conflicts of interest related to this research or this manuscript. The clinical trial registration number with clinicaltrials.gov is NCT03124186. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2klDOkB
https://ift.tt/2klDOkB
Effectiveness of Physiotherapy Interventions on Spasticity in People with Multiple Sclerosis. A Systematic Review and Meta-Analysis
Objective To examine the effectiveness of physiotherapy (PT) interventions on spasticity in people with multiple sclerosis (PwMS). Design A systematic search was performed using PRISMA guidance. Studies evaluate the effect of PT interventions on spasticity were included. PwMS, spasticity, disability and PT interventions characteristics were extracted in included studies. Level of evidence was synthesized by GRADE approach. Meta-analyses were performed by calculating Hedges g at 95% confidence interval. Results A total of 29 studies were included in the review, and 25 in the meta-analyses. The included PT interventions were exercise therapy, electrical stimulation, radial shock wave therapy, vibration, and standing. The review and meta-analyses showed different evidences of benefits and non-benefits for PT interventions on some spasticity outcomes. The best quality evidences were for beneficial effects of exercise therapy especially robot gait training, and outpatient exercise programs on self-perceived spasticity and muscle tone respectively. The review results were positive regarding the acute effects, follow-up measurements, safety, progressive MS, and non-ambulatory PwMS. The included articles were heterogeneous and badly reported in PT interventions and PwMS characteristics. Conclusion PT interventions can be safe and beneficial option for spasticity in PwMS. No firm conclusion can be drawn on overall spasticity. Further researches in different spasticity aspects are needed. Corresponding Author: Mohammad Etoom PT, PhD, Physical Therapy Department, Al-Isra University, Amman-Jordan, Email: mohammed.etoom2016@gmail.com Financial support and conflict of interest: None The manuscript has not been previously presented in any scientific meeting or publication. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2GKynnW
https://ift.tt/2GKynnW
Functional Outcome of Elderly Hip Fracture Patients is not Affected By Pre-Fracture Dementia
Objective The aim of the study was to examine whether a diagnosis of pre-fracture Dementia (PFD) affects functional outcome at discharge from a geriatric rehabilitation setting. Design A total of 211 consecutive elderly hip fracture patients were evaluated retrospectively. We used the Functional Independence Measure (FIM) and analyzed data by t-test, chi square-test and multiple linear regression analysis. Results Patients with PFD were older (P = 0.001), presented with lower Mini-Mental State Examination (MMSE) scores (P
https://ift.tt/2IFLsoB
https://ift.tt/2IFLsoB
When will every EMT wear a body camera?
An EMT's attack of a restrained patient is a reminder for all leaders to discuss response to provocations and consider body-worn cameras to capture the EMS point-of-view
https://ift.tt/2s6OaIq
Dear new EMT or paramedic: It's OK to ask for help
In EMS, most providers learn their most important lessons by doing; here are three lessons learned that you should never forget – no matter how long you've been in EMS
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Video: Celebrating EMS Week 2018
Departments are marking the occasion by enhancing their training skills, teaching lifesaving lessons and reminding providers to always have their partner's back
https://ift.tt/2KOK7bo
Oral Over-the-Counter Benzocaine Products: Drug Safety Communication - Risk of Serious and Potentially Fatal Blood Disorder
[Posted 05/23/2018] AUDIENCE: Pediatrics, Dentistry, Consumer, Health Professional, Pharmacy ISSUE: The FDA is warning that over-the-counter (OTC) oral drug products containing benzocaine should not be used to treat infants and children younger...
https://ift.tt/2GJZcZw
Oral Over-the-Counter Benzocaine Products: Drug Safety Communication - Risk of Serious and Potentially Fatal Blood Disorder
[Posted 05/23/2018] AUDIENCE: Pediatrics, Dentistry, Consumer, Health Professional, Pharmacy ISSUE: The FDA is warning that over-the-counter (OTC) oral drug products containing benzocaine should not be used to treat infants and children younger...
https://ift.tt/2GJZcZw
How DahlgrenDecon is the fastest, most effective decontamination solution
DahlgrenDecon can neutralize fentanyl in about five minutes and is the most effective decontamination for other drugs, chemical and biological agents as well as toxic industrial chemicals and materials
https://ift.tt/2IXKVh7
Atomic Layer Deposition of Vanadium Dioxide and a Temperature-dependent Optical Model
Thin films (100-1000 Å) of vanadium dioxide (VO2) were created by atomic-layer deposition (ALD) on sapphire substrates. Following this, the optical properties were characterized through the metal-insulator transition of VO2. From the measured optical properties, a model was created to describe the tunable refractive index of VO2.
https://ift.tt/2J0gh6O
Stoichiometry of the Heteromeric Nicotinic Receptors of the Renshaw Cell
Neuronal nicotinic acetylcholine receptors (nAChRs) are pentamers built from a variety of subunits. Some are homomeric assemblies of α subunits, others heteromeric assemblies of α and β subunits which can adopt two stoichiometries (2α:3β or 3α:2β). There is evidence for the presence of heteromeric nAChRs with the two stoichiometries in the CNS, but it has not yet been possible to identify them at a given synapse. The 2α:3β receptors are highly sensitive to agonists, whereas the 3α:2β stoichiometric variants, initially described as low sensitivity receptors, are indeed activated by low and high concentrations of ACh. We have taken advantage of the discovery that two compounds (NS9283 and Zn) potentiate selectively the 3α:2β nAChRs to establish (in mice of either sex) the presence of these variants at the motoneuron-Renshaw cell (MN-RC) synapse. NS9283 prolonged the decay of the two-component EPSC mediated by heteromeric nAChRs. NS9283 and Zn also prolonged spontaneous EPSCs involving heteromeric nAChRs, and one could rule out prolongations resulting from AChE inhibition by NS9283. These results establish the presence of 3α:2β nAChRs at the MN-RC synapse. At the functional level, we had previously explained the duality of the EPSC by assuming that high ACh concentrations in the synaptic cleft account for the fast component and that spillover of ACh accounts for the slow component. The dual ACh sensitivity of 3α:2β nAChRs now allows to attribute to these receptors both components of the EPSC.
SIGNIFICANCE STATEMENT Heteromeric nicotinic receptors assemble α and β subunits in pentameric structures, which can adopt two stoichiometries: 3α:2β or 2α:3β. Both stoichiometric variants are present in the CNS, but they have never been located and characterized functionally at the level of an identified synapse. Our data indicate that 3α:2β receptors are present at the spinal cord synapses between motoneurons and Renshaw cells, where their dual mode of activation (by high concentrations of ACh for synaptic receptors, by low concentrations of ACh for extrasynaptic receptors) likely accounts for the biphasic character of the synaptic current. More generally, 3α:2β nicotinic receptors appear unique by their capacity to operate both in the cleft of classical synapses and at extrasynaptic locations.
https://ift.tt/2KMVoZS
Palladin Is a Neuron-Specific Translational Target of mTOR Signaling That Regulates Axon Morphogenesis
The mTOR signaling pathway regulates protein synthesis and diverse aspects of neuronal morphology that are important for brain development and function. To identify proteins controlled translationally by mTOR signaling, we performed ribosome profiling analyses in mouse cortical neurons and embryonic stem cells upon acute mTOR inhibition. Among proteins whose translation was significantly affected by mTOR inhibition selectively in neurons, we identified the cytoskeletal regulator protein palladin, which is localized within the cell body and axons in hippocampal neurons. Knockdown of palladin eliminated supernumerary axons induced by suppression of the tuberous sclerosis complex protein TSC1 in neurons, demonstrating that palladin regulates neuronal morphogenesis downstream of mTOR signaling. Our findings provide novel insights into an mTOR-dependent mechanism that controls neuronal morphogenesis through translational regulation.
SIGNIFICANCE STATEMENT This study reports the discovery of neuron-specific protein translational responses to alterations of mTOR activity. By using ribosome profiling analysis, which can reveal the location and quantity of translating ribosomes on mRNAs, multiple aspects of protein translation were quantitatively analyzed in mouse embryonic stem cells and cortical neurons upon acute mTOR inhibition. Neurons displayed distinct patterns of ribosome occupancy for each codon and ribosome stalling during translation at specific positions of mRNAs. Importantly, the cytoskeletal regulator palladin was identified as a translational target protein of mTOR signaling in neurons. Palladin operates downstream of mTOR to modulate axon morphogenesis. This study identifies a novel mechanism of neuronal morphogenesis regulated by mTOR signaling through control of translation of the key protein palladin.
https://ift.tt/2GITQ0s
Dopamine Triggers CTCF-Dependent Morphological and Genomic Remodeling of Astrocytes
Dopamine is critical for processing of reward and etiology of drug addiction. Astrocytes throughout the brain express dopamine receptors, but consequences of astrocytic dopamine receptor signaling are not well established. We found that extracellular dopamine triggered rapid concentration-dependent stellation of astrocytic processes that was not a result of dopamine oxidation but instead relied on both cAMP-dependent and cAMP-independent dopamine receptor signaling. This was accompanied by reduced duration and increased frequency of astrocytic Ca2+ transients, but little effect on astrocytic voltage-gated potassium channel currents. To isolate possible mechanisms underlying these structural and functional changes, we used whole-genome RNA sequencing and found prominent dopamine-induced enrichment of genes containing the CCCTC-binding factor (CTCF) motif, suggesting involvement of chromatin restructuring in the nucleus. CTCF binding to promoter sites bidirectionally regulates gene transcription and depends on activation of poly-ADP-ribose polymerase 1 (PARP1). Accordingly, antagonism of PARP1 occluded dopamine-induced changes, whereas a PARP1 agonist facilitated dopamine-induced changes on its own. These results indicate that astrocyte response to elevated dopamine involves PARP1-mediated CTCF genomic restructuring and concerted expression of gene networks. Our findings propose epigenetic regulation of chromatin landscape as a critical factor in the rapid astrocyte response to dopamine.
SIGNIFICANCE STATEMENT Although dopamine is widely recognized for its role in modulating neuronal responses both in healthy and disease states, little is known about dopamine effects at non-neuronal cells in the brain. To address this gap, we performed whole-genome sequencing of astrocytes exposed to elevated extracellular dopamine and combined it with evaluation of effects on astrocyte morphology and function. We demonstrate a temporally dynamic pattern of genomic plasticity that triggers pronounced changes in astrocyte morphology and function. We further show that this plasticity depends on activation of genes sensitive to DNA-binding protein CTCF. Our results propose that a broad pattern of astrocyte responses to dopamine specifically relies on CTCF-dependent gene networks.
https://ift.tt/2LqmtTS
Temporal Response Properties of Accessory Olfactory Bulb Neurons: Limitations and Opportunities for Decoding
The vomeronasal system (VNS) is a major vertebrate chemosensory system that functions in parallel to the main olfactory system (MOS). Despite many similarities, the two systems dramatically differ in the temporal domain. While MOS responses are governed by breathing and follow a subsecond temporal scale, VNS responses are uncoupled from breathing and evolve over seconds. This suggests that the contribution of response dynamics to stimulus information will differ between these systems. While temporal dynamics in the MOS are widely investigated, similar analyses in the accessory olfactory bulb (AOB) are lacking. Here, we have addressed this issue using controlled stimulus delivery to the vomeronasal organ of male and female mice. We first analyzed the temporal properties of AOB projection neurons and demonstrated that neurons display prolonged, variable, and neuron-specific characteristics. We then analyzed various decoding schemes using AOB population responses. We showed that compared with the simplest scheme (i.e., integration of spike counts over the entire response period), the division of this period into smaller temporal bins actually yields poorer decoding accuracy. However, optimal classification accuracy can be achieved well before the end of the response period by integrating spike counts within temporally defined windows. Since VNS stimulus uptake is variable, we analyzed decoding using limited information about stimulus uptake time, and showed that with enough neurons, such time-invariant decoding is feasible. Finally, we conducted simulations that demonstrated that, unlike the main olfactory bulb, the temporal features of AOB neurons disfavor decoding with high temporal accuracy, and, rather, support decoding without precise knowledge of stimulus uptake time.
SIGNIFICANCE STATEMENT A key goal in sensory system research is to identify which metrics of neuronal activity are relevant for decoding stimulus features. Here, we describe the first systematic analysis of temporal coding in the vomeronasal system (VNS), a chemosensory system devoted to socially relevant cues. Compared with the main olfactory system, timescales of VNS function are inherently slower and variable. Using various analyses of real and simulated data, we show that the consideration of response times relative to stimulus uptake can aid the decoding of stimulus information from neuronal activity. However, response properties of accessory olfactory bulb neurons favor decoding schemes that do not rely on the precise timing of stimulus uptake. Such schemes are consistent with the variable nature of VNS stimulus uptake.
https://ift.tt/2LoMyCW
Encoding of Serial Order in Working Memory: Neuronal Activity in Motor, Premotor, and Prefrontal Cortex during a Memory Scanning Task
We have adapted Sternberg's context-recall task to investigate the neural mechanisms of encoding serial order information in working memory, in 2 male rhesus monkeys. We recorded from primary motor, premotor, and dorsolateral prefrontal cortex while the monkeys performed the task. In each cortical area, most neurons displayed marked modulation of activity during the list presentation period of the task, whereas the serial order of the stimuli needed to be encoded in working memory. The activity of many neurons changed in a consistent manner over the course of the list presentation period, without regard to the location of the stimuli presented. Remarkably, these neurons encoded serial position information in a relative (rather than absolute) manner across different list lengths. In addition, many neurons showed activity related to both location and serial position, in the form of an interaction effect. Surprisingly, the activity of these neurons was often modulated by the location of stimuli presented before the epoch in which the activity changes occurred. In motor and premotor areas, a large proportion of neurons with list presentation activity also showed direction-related activity during the response phase, whereas in prefrontal cortex most cells showed only list presentation effects. These results show that many neurons had a heterogeneous functionality by representing distinct task variables at different periods of the task. Finally, potential confounds could not account for the effects observed. For these reasons, we conclude that these neurons were indeed participating in sequence encoding in working memory.
SIGNIFICANCE STATEMENT Traditionally, primary motor, premotor, and prefrontal areas have been considered to be mainly engaged in motor output, visuomotor transformation, and higher cognitive functions, respectively. Here we show that neurons in all three cortical regions participate in the encoding of a sequence of spatial stimuli in working memory. Furthermore, a central question in cognitive neuroscience has been the manner in which the position of an item within a sequence is encoded in the brain. Our findings provide direct neurophysiological support for a specific hypothesis from cognitive psychology: that of relative coding of serial order.
https://ift.tt/2Lrq3gr
Early Interventions for the Prevention of Posttraumatic Stress Symptoms in Survivors of Critical Illness: A Qualitative Systematic Review
Objectives: Posttraumatic stress disorder among survivors of critical illness is of public health importance, as it is common and reduces patient quality of life. The objective of this systematic review was to collate the world's literature on interventions aimed at preventing posttraumatic stress disorder among survivors of critical illness. Data Sources: We performed a search of CENTRAL, MEDLINE, EMBASE, CINAHL, and clinical trials registry platforms, with no restriction to language using a comprehensive strategy. Study Selection: Study inclusion criteria were as follows: 1) adult human subjects, 2) patients treated in an ICU setting, 3) intervention arm aimed at reducing posttraumatic stress disorder symptoms, 4) use of a control arm, and 5) an outcome measure assessing development of acute stress or posttraumatic stress disorder symptoms. Data Extraction: We performed a qualitative analysis to collate and summarize effects of identified interventions according to the recommended methodology from the Cochrane Handbook. Data Synthesis: Seventeen studies met all inclusion and no exclusion criteria. There was heterogeneity in interventions and outcome measures used. All studies had some concern for risk of bias as per the Cochrane tool for assessing risk of bias. In eight of 12 studies (67%) testing early interventions (i.e., initiated in the ICU course) and one of five studies (20%) testing delayed interventions following ICU discharge, posttraumatic stress disorder symptoms were decreased among the intervention group compared with controls. Conclusions: Despite a paucity of high-quality clinical investigations, the preponderance of evidence to date suggests that 1) posttraumatic stress disorder among survivors of critical illness may be preventable and 2) early interventions may be the most effective. All authors have made substantial contributions to this article; contributed to the development of the selection criteria, the risk of bias assessment strategy, and data extraction criteria; read and contributed substantially to revision of the final article; and approved the article in its final form. Drs. M. B. Roberts and B. W. Roberts developed the search strategy and drafted the article. B. W. Roberts supervised all aspects of the study design and takes responsibility for the article as a whole. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Dr. Jones' institution received funding from Roche Diagnostics, AstraZeneca, Janssen, and Hologic (investigator for an ongoing study). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: roberts-brian-w@cooperhealth.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
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https://ift.tt/2IGB7Zw
De novo FBXO11 mutations are associated with intellectual disability and behavioural anomalies
Abstract
Intellectual disability (ID) has an estimated prevalence of 1.5–2%. In most affected individuals, its genetic basis remains unclear. Whole exome sequencing (WES) studies have identified a multitude of novel causative gene defects and have shown that a large proportion of sporadic ID cases results from de novo mutations. Here, we present two unrelated individuals with similar clinical features and deleterious de novo variants in FBXO11 detected by WES. Individual 1, a 14-year-old boy, has mild ID as well as mild microcephaly, corrected cleft lip and alveolus, hyperkinetic disorder, mild brain atrophy and minor facial dysmorphism. WES detected a heterozygous de novo 1 bp insertion in the splice donor site of exon 3. Individual 2, a 3-year-old boy, showed ID and pre- and postnatal growth retardation, postnatal mild microcephaly, hyperkinetic and restless behaviour, as well as mild dysmorphism. WES detected a heterozygous de novo frameshift mutation. While ten individuals with ID and de novo variants in FBXO11 have been reported as part of larger studies, only one of the reports has some additional clinical data. Interestingly, the latter individual carries the identical mutation as our individual 2 and also displays ID, intrauterine growth retardation, microcephaly, behavioural anomalies, and dysmorphisms. Thus, we confirm deleterious de novo mutations in FBXO11 as a cause of ID and start the delineation of the associated clinical picture which may also comprise postnatal microcephaly or borderline small head size and behavioural anomalies.
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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...
