Identification of a novel DNMT1 mutation in a Chinese patient with hereditary sensory and autonomic neuropathy type IE

DNA methyltransferase 1 (EC 2.1.1.37), encoded by DNMT1 gene, is one of key enzymes in maintaining DNA methylation patterns of the human genome. It plays a crucial role in embryonic development, imprinting and...

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Prevalence and antibiotic susceptibility pattern of CTX-M type extended-spectrum β-lactamases among clinical isolates of gram-negative bacilli in Jimma, Ethiopia

The prevalence of extended-spectrum β-lactamases (ESBLs) have been reported in clinical isolates obtained from various hospitals in Ethiopia. However, there is no data on the prevalence and antibiotic suscepti...

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Contents

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Editorial Board

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Herbert Ross: Among the First in the U. S. to Benefit from a New Surgical Navigation System

The Department of Otorhinolaryngology-Head and Neck Surgery at McGovern Medical School at UTHealth was the first site in the United...

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UTHealth Otorhinolaryngology Residents Named HSO Resident Scientific Research Winners

Two UTHealth otorhinolaryngology residents were among four Houston-area residents invited to present their research as winners of the Houston Society...

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Dr. Ibrahim Alava, Dr. William Yao and Dr. Sancak Yuksel Receive Dean’s Teaching Excellence Awards

Ibrahim "Trey" Alava, MD; William Yao, MD; and Sancak Yuksel, MD, have been recognized with McGovern Medical School's 2018 Dean's...

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UT Physicians Otorhinolaryngology Expands Its Annual Head and Neck Cancer Screening from the Texas Medical Center to Houston Suburbs

The Department of Otorhinolaryngology—Head and Neck Surgery at McGovern Medical School at UTHealth offered four free cancer screening clinics last...

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Time Course Changes of the Mechanical Properties of the Iris Pigment Epithelium in a Rat Chronic Ocular Hypertension Model

Background. The flow field of aqueous humor correlates to the stiffness of iris pigment epithelium (IPE) which acts as a wall of posterior chamber. We focus on the variations of IPE stiffness in a rat ocular hypertension (OHT) model, so as to prepare for exploring the mechanism of duration of OHT. Methods. Episcleral venous cauterization (EVC) was applied on one eye of male adult Sprague-Dawley rats to induce chronic high intraocular pressure. According to the duration of OHT (0, 1, 2, 4, and 8 weeks), rats were randomly divided into Gw0, Gw1, Gw2, Gw4, and Gw8. Atomic force microscope (AFM) analysis was applied to test IPE stiffness in three regions: iris root, mid-periphery, and pupillary-margin in each group. Histological changes of IPE were also examined in Gw4 and Gw8. Results. There was an overall growing tendency of IPE stiffness in EVC eye. IPE in EVC eye was significantly stiffer than fellow eye in Gw2, Gw4, and Gw8 (in iris root, mid-periphery, and pupillary-margin, p

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The Influence of Position of the Displaced Lesser Trochanter on Clinical Outcome of Unstable Trochanteric Femur Fractures in the Elderly

Purpose. This study aimed to evaluate whether position of the displaced lesser trochanter affected clinical outcome in the treatment of unstable trochanteric fractures with intramedullary fixation. Patients and Methods. Patients with unstable trochanteric fractures and displaced lesser trochanter who received intramedullary fixation were retrospectively reviewed in this study. Based on displacement distance of the lesser trochanter and whether the lesser trochanter was reduced operatively, patients were divided into three groups: patients with the displaced lesser trochanter less than 1cm (Group A), those with the displaced lesser trochanter more than 1 cm without operative reduction (Group B), or those with operative reduction (Group C). The surgical time, reduction quality, Harris Hip Score (HHS), Visual Analog Score (VAS), and complication rate were reviewed. Results. There were 42 patients in Group A, 33 in Group B, and 36 in Group C with comparable demographic characteristics. The surgical time was significantly longer in Group C (P=0.009), compared with Groups A and B. Fracture reduction quality was comparable with over 85% good reduction among the three groups. The VAS score was significantly higher in Group B (P=0.023) without significant difference between Groups A and B. The HHS score was slightly lower in Group B, but it did not reach significant difference. The complication rate was statistically higher in Group B (p=0.043) than Groups A and C. Conclusion. The severe displaced lesser trochanter may increase postoperative complications and postoperative pain in the treatment of unstable trochanteric femur fractures. However, the displaced lesser trochanter may not affect hip function.

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Construction of a Multilayered Mesenchymal Stem Cell Sheet with a 3D Dynamic Culture System

This article provides an efficient and feasible method for constructing multilayered stem cell sheets with favorable stem cell property.

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What if EMS won a $1 billion lottery jackpot?

Big dreams to improve EMS with a windfall of funding for safety, health and wellness, research and leadership development

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What if EMS won a $1 billion lottery jackpot?

Big dreams to improve EMS with a windfall of funding for safety, health and wellness, research and leadership development

https://ift.tt/2ytDMyo

An In Vivo Method for Evaluating the Gut-Blood Barrier and Liver Metabolism of Microbiota Products

The access of nutrients, microbiota metabolites and medicines to the circulation is controlled by the gut-blood barrier (GBB). We describe a direct method for measuring the GBB permeability in vivo, which, in contrast to commonly used indirect methods, is virtually not affected by liver and kidney functions.

https://ift.tt/2J7XgwJ

Scalable Fabrication of Stretchable, Dual Channel, Microfluidic Organ Chips

Here, we present a protocol that describes the fabrication of stretchable, dual channel, organ chip microfluidic cell culture devices for recapitulating organ-level functionality in vitro.

https://ift.tt/2pYvDNY

Role of BMP-9 in human liver disease

We read with interest the article by Breitkopf-Heinlein et al,1 investigating the role of bone morphogenetic protein (BMP)-9 in liver regeneration and fibrosis. In mice, the authors demonstrate that BMP-9, a member of the transforming growth factor-β family, is primarily produced by hepatic stellate cells (HSCs) and is a profibrogenic factor. Inhibition or knockout of BMP-9 reduced liver fibrosis, while the recombinant protein increased the proliferation and migration of human HSCs. However, as shown in figure 1H and I of that study, rhBMP-9 did not upregulate fibrosis markers (eg, collagen I, fibronectin, platelet-derived growth factor B and α smooth muscle actin). While BMP-9 expression increased during the activation of primary human HSCs, the authors were unable to demonstrate a correlation between human hepatic BMP-9 expression and liver fibrosis stage from a publicly available microarray dataset.

We analysed multiple publicly available microarray datasets; consistent with their findings, differential expression...

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DYRK1A modulates c-MET in pancreatic ductal adenocarcinoma to drive tumour growth

Background and aims

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumour with a poor prognosis using current treatments. Targeted therapies may offer a new avenue for more effective strategies. Dual-specificity tyrosine regulated kinase 1A (DYRK1A) is a pleiotropic kinase with contradictory roles in different tumours that is uncharacterised in PDAC. Here, we aimed to investigate the role of DYRK1A in pancreatic tumorigenesis.

Design

We analysed DYRK1A expression in PDAC genetic mouse models and in patient samples. DYRK1A function was assessed with knockdown experiments in pancreatic tumour cell lines and in PDAC mouse models with genetic reduction of Dyrk1a dosage. Furthermore, we explored a mechanistic model for DYRK1A activity.

Results

We showed that DYRK1A was highly expressed in PDAC, and that its protein level positively correlated with that of c-MET. Inhibition of DYRK1A reduced tumour progression by limiting tumour cell proliferation. DYRK1A stabilised the c-MET receptor through SPRY2, leading to prolonged activation of extracellular signal-regulated kinase signalling.

Conclusions

These findings reveal that DYRK1A contributes to tumour growth in PDAC, at least through regulation of c-MET accumulation, suggesting that inhibition of DYRK1A could represent a novel therapeutic target for PDAC.

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Administration of ferrous sulfate drops has significant effects on the gut microbiota of iron-sufficient infants: a randomised controlled study

We read with interest the work by Jaeggi et al1 and Paganinni et al2 and commend their efforts. Despite differences in iron concentration, infants' age and sequencing techniques, both studies demonstrate unfavourable iron effects on gut microbiota with decreased abundance of bifidobacteria and lactobacillus, and increased abundance of pathogenic bacteria in iron-deficient/anaemic Kenyan infants.

We have investigated changes in gut microbial composition due to iron fortification or supplementation in healthy, Swedish infants. Iron-sufficient infants at 6 months of age were randomly allocated to receive low-iron-fortified formula (1.2 mg Fe/day; n=24), high-iron-fortified formula (6.6 mg Fe/day; n=24) or no-added-iron formula with liquid ferrous sulfate supplementation (iron drops; 6.6 mg Fe/day; n=24) for 45 days. All participants gave their informed consent before inclusion through parents or legal guardians. Total iron intake was 1.2, 6.4 and 5.7 mg/day (all differences p<0.01) in the low-iron, high-iron and iron-drops group, respectively. Stool samples were collected before...

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MicroRNA-10a, -210 and -563 as circulating biomarkers for Ossification of the Posterior Longitudinal Ligament

Publication date: Available online 20 October 2018

Source: The Spine Journal

Author(s): Chen Xu, Hao Zhang, Wenchao Zhou, Huiqiao Wu, Xiaolong Shen, Yuanyuan Chen, Mingfang Liao, Yang Liu, Wen Yuan

ABSTRACT

Background Context

The presence of ossification of posterior longitudinal ligament (OPLL) can lead to symptomatic spinal cord compression and myelopathy. The surgical approach in patients with myelopathy is influenced by the presence of OPLL. Diagnose of OPLL currently requires computed tomography which incurs a large dose of radiation. Circulating disease-specific microRNAs (miRNAs) may serve as promising diagnostic markers with no radiation and easy accessibility for OPLL patients.

Purpose

The purpose of this study is to evaluate the accuracy and significance of OPLL-specific microRNAs in discriminating OPLL from normal and intervertebral disc degenerated (IDD) patients by detecting the microRNAs' plasma level.

Study Design/patient samples

The level of microRNAs in OPLL patients' plasma or serum were detected and compared to that of normal and IDD patients to evaluate the accuracy and significance of diagnosing OPLL.

Methods

Taking advantage of the high through-put microRNA sequencing data, we selectively tested the ten most differentially regulated microRNAs in patients with: 1)radiologically diagnosed OPLL (n=68), 2) radiologically diagnosed disc herniated patients with no evidence of OPLL (n=45), 3) non-OPLL and non-myelopathy patients (n=53).The feasibility of the biomarkers in identifying OPLL was assessed through analysis of sensitivity, specificity, accuracy, negative predictive value, positive predictive value, and area under the curve (AUC) values.

Results

Of the ten miRNAs validated,miR-10a-3p, miR-10a-5p, miR-563, miR-210-3p and miR-218-3p showed significance between OPLL and non-OPLL blood samples. While miR-10a-5p, miR-563 and miR-210-3p showed high accuracy and significance in identifying OPLL from other groups individually, and an index that combines these miRNAs achieved the highest accuracy and AUC (area under curve) among these individual miRNAs.

Conclusion

Analysis of miR-10a-5p, miR-563 and miR-210-3p may be of important value in diagnosing OPLL. These markers maybe useful in a clinical setting in the early detection of OPLL patients by blood testing.

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EVIDENCE OF IMPAIRED PAIN MODULATION IN ADOLESCENTS WITH IDIOPATHIC SCOLIOSIS AND CHRONIC BACK PAIN

Publication date: Available online 19 October 2018

Source: The Spine Journal

Author(s): Alisson R. Teles, Don Daniel Ocay, Abdulaziz Bin Shebreen, Andrew Tice, Neil Saran, Jean A. Ouellet, Catherine E. Ferland

Abstract

Background context

Although 40% of adolescent idiopathic scoliosis (AIS) patients present with chronic back pain, the pathophysiology and underlying pain mechanisms remain poorly understood. We hypothesized that development of chronic pain syndrome in AIS is associated with alterations in pain modulatory mechanisms.

Purpose

To identify the presence of sensitization in nociceptive pathways and to assess the efficacy of the diffuse noxious inhibitory control in patients with AIS presenting with chronic back pain.

Study design

Cross-sectional study.

Patient sample

Ninety-four patients diagnosed with AIS and chronic back pain.

Outcome measures

Quantitative sensory testing (QST) assessed pain modulation and self-reported questionnaires were used to assess pain burden and health-related quality of life.

Methods

Patients underwent a detailed pain assessment using a standard and validated quantitative sensory testing (QST) protocol. The measurements included mechanical detection thresholds (MDT), pain pressure threshold (PPT), heat pain threshold (HPT), heat tolerance threshold (HTT), and a conditioned pain modulation (CPM) paradigm. Altogether, these tests measured changes in regulation of the neurophysiology underlying the nociceptive processes based on the patient's pain perception. Funding was provided by The Louise and Alan Edwards Foundation and The Shriners Hospitals for Children.

Results

Efficient pain inhibitory response was observed in 51.1% of patients, while 21.3% and 27.7% had sub-optimal and inefficient CPM, respectively. Temporal summation of pain was observed in 11.7% of patients. Significant correlations were observed between deformity severity and pain pressure thresholds (P = 0.023) and CPM (P=0.017), neuropathic pain scores and pain pressure thresholds (P=0.015) and temporal summation of pain (P=0.047), and heat temperature threshold and pain intensity (P=0.048).

Conclusions

Chronic back pain has an impact in the quality of life of adolescents with idiopathic scoliosis. We demonstrated a high prevalence of impaired pain modulation in this group. The association between deformity severity and somatosensory dysfunction may suggest that spinal deformity can be a trigger for abnormal neuroplastic changes in this population contributing to chronic pain syndrome.

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Detection of Heterodimerization of Protein Isoforms Using an in Situ Proximity Ligation Assay

Here, we show how to use a Proximity Ligation Assay (PLA) to visualize MST1/MST2 heterodimerization in fixed cells with high sensitivity.

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Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE): a multicenter observational study

Abstract

Background

Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and ¹⁸F-fluorodeoxyglucose positron emission tomography with computed tomography (¹⁸F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR.

Methods

The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and ¹⁸F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival.

Discussion

If the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped.

Trial registration

The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341.

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Rigor prophylaxis in stage IV melanoma and renal cell carcinoma patients treated with high dose IL-2

Abstract

Background

Rigors are a significant adverse event during interleukin-2 (IL2) therapy for metastatic melanoma and renal cell carcinoma. Meperidine has been a mainstay for rigor prophylaxis but there is a paucity of data regarding possible alternatives.

Methods

Ninety one patients receiving IL2 therapy for metastatic renal cell carcinoma and melanoma at Huntsman Cancer institute (HCI), Utah from May 2009 to October 2016 were retrospectively evaluated for rigor prophylaxis. Forty two patients received meperidine and 49 received tramadol. Rigors were tabulated using the proxy of number of doses of as needed (PRN) rigor medications and normalized by IL2 doses. Other outcomes of fever, hypotension, and renal insufficiency were noted on a binary scale and normalized by cycles. Statistical analysis was performed utilizing univariate and multivariate negative binomial models.

Results

Ninety one patients were identified with metastatic melanoma or RCC who received high dose IL2 therapy. Forty two received meperidine and 49 received tramadol prophylaxis for rigors. Univariate negative binomial analysis shows incidence rate ratios (IRR): fever 0.41 (95% CI 0.28–0.62, p-value < 0.001), hypotension 1.7 (95% CI 1.11–2.61, p-value 0.015), renal insufficiency 0.58 (95% CI 0.35–0.98, p-value 0.041), rigors per all PRN meds 1.01 (95% CI 0.79–1.28, p-value 0.964), and rigors via opioid PRN meds 0.85 (95% CI 0.67–1.07, p-value 0.168). Multivariate negative binomial analysis shows IRR: fever 0.59 (95% CI 0.28–1.24, p-value 0.163), hypotension 0.93 (95% CI 0.43–2.03, p-value 0.864), renal insufficiency 1.1 (95% CI 0.52–2.32, p-value 0.807), rigors per al PRN meds 0.92 (95% CI 0.67–1.26, p-value 0.604), and rigors via opioid PRN 0.9 (95% CI 0.65–1.26, p-value 0.554).

Conclusion

Univariate models indicated meperidine pre-treatment was associated with significantly lower rates of fever and renal insufficiency whereas tramadol was associated with significantly lower rate of hypotension. However, when controlled for demographics and other treatment differences, these differences were no longer significant.

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Impact of renal impairment on outcomes after autologous stem cell transplantation in multiple myeloma: a multi-center, retrospective cohort study

Abstract

Background

Renal impairment (RI) is a negative prognostic factor in Multiple Myeloma (MM) and affected patients are often excluded from autologous stem cell transplantation (ASCT). However, it remains unclear whether historically inferior outcome data still hold true.

Methods

From a total of 475 eligible MM patients who had undergone ASCT between 1998 and 2016, 374 were included in this multi-centric retrospective cohort study. Renal function was determined both at the time of MM diagnosis and ASCT by estimated glomerular filtration rate (eGFR according to the MDRD formula, RI defined as eGFR < 60 ml/min/1.73m²). Patients were categorized into 3 groups: A) no RI diagnosis and ASCT, B) RI at diagnosis with normalization before ASCT and C) RI both at the time of diagnosis and ASCT. Log-rank testing was used for overall and progression-free survival (OS, PFS) analysis.

Conclusion

While severe RI at MM diagnosis confers a risk of shorter OS, MM progression after ASCT is not affected by any stage of renal failure. It can be concluded that ASCT can be safely carried out in MM patients with mild to moderate RI and should be pro-actively considered in those with severe RI.

Results

When comparing all groups, no difference in OS and PFS was found (p = 0.319 and p = 0.904). After further stratification according to the degree of RI at the time of diagnosis, an OS disadvantage was detected for patients with an eGFR < 45 ml/min/m². PFS was not affected by any RI stage.

https://ift.tt/2yQppUj

Groove Pancreatitis Masquerading as Pancreatic Carcinoma—Detected on 18 F-FDG PET/CT

Abstract

Groove pancreatitis is a rare form of chronic pancreatitis that affects the groove area adjacent to the second part of the duodenum. Clinical and biochemical features often overlap with other subsets of chronic pancreatitis, while the imaging features resemble that of carcinoma of the head of pancreas. We present a 38-year-old man with abdominal pain, nausea, vomiting, and loss of weight who underwent ¹⁸F-FDG PET/CT to rule out a pancreatic malignancy. PET/CT imaging features of groove pancreatitis are distinct from the other subsets of chronic pancreatitis, such as alcoholic and autoimmune pancreatitis, and helpful in the diagnosis and planning further management of the patient.

https://ift.tt/2Ewr8V2

Dysfunctional effort-based decision-making underlies apathy in genetic cerebral small vessel disease

Abstract

Apathy is a syndrome of reduced motivation that commonly occurs in patients with cerebral small vessel disease, including those with the early onset form, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). The cognitive mechanisms underlying apathy are poorly understood and treatment options are limited. We hypothesized that disrupted effort-based decision-making, the cognitive process by which potential rewards and the effort cost required to obtain them is integrated to drive behaviour, might underlie the apathetic syndrome. Nineteen patients with a genetic diagnosis of CADASIL, as a model of 'pure' vascular cognitive impairment, and 19 matched controls were assessed using two different behavioural paradigms and MRI. On a decision-making task, participants decided whether to accept or reject sequential offers of monetary reward in return for exerting physical effort via handheld dynamometers. Six levels of reward and six levels of effort were manipulated independently so offers spanned the full range of possible combinations. Choice, decision time and force metrics were recorded. Each participant's effort and reward sensitivity was estimated using a computational model of choice. On a separate eye movement paradigm, physiological reward sensitivity was indexed by measuring pupillary dilatation to increasing monetary incentives. This metric was related to apathy status and compared to the behavioural metric of reward sensitivity on the decision-making task. Finally, high quality diffusion imaging and tract-based spatial statistics were used to determine whether tracts linking brain regions implicated in effort-based decision-making were disrupted in apathetic patients. Overall, apathetic patients with CADASIL rejected significantly more offers on the decision-making task, due to reduced reward sensitivity rather than effort hypersensitivity. Apathy was also associated with blunted pupillary responses to incentives. Furthermore, these independent behavioural and physiological markers of reward sensitivity were significantly correlated. Non-apathetic patients with CADASIL did not differ from controls on either task, whilst actual motor performance of apathetic patients in both tasks was also normal. Apathy was specifically associated with reduced fractional anisotropy within tracts connecting regions previously associated with effort-based decision-making. These findings demonstrate behavioural, physiological and anatomical evidence that dysfunctional effort-based decision-making underlies apathy in patients with CADASIL, a model disorder for sporadic small vessel disease. Reduced incentivization by rewards rather than hypersensitivity to effort costs drives this altered pattern of behaviour. The study provides empirical evidence of a cognitive mechanism for apathy in cerebral small vessel disease, and identifies a promising therapeutic target for interventions to improve this debilitating condition.

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Lung squamous cell carcinoma with solitary ocular metastasis and its successful treatment with thoracic surgery and chemotherapy: an interesting and rare case report

Abstract

Background

The incidence of ocular metastasis from lung cancer is reported to be 0.1–7%, with adenocarcinoma and small cell lung cancer accounting for the highest proportions of these cases. The majority of cases involves metastasis to more than one other distal organ in addition to the eye. Here, we report for the first time, a case of lung squamous cell carcinoma with solitary symptomatic ocular metastasis as the initial manifestation that was managed by a multidisciplinary treatment (MDT).

Case presentation

A woman presented at the ophthalmology department of hospital with a 1-week history of left eye pain and blurred vision. Systemic examination led to the diagnosis of central lung cancer in the right lower lobe with ocular metastasis. After consultations with an MDT, including specialists from the surgery, internal medicine, ophthalmology, radiotherapy and imaging departments, the patient underwent surgery and chemotherapy. Her eye symptoms disappeared, and the ocular lesion was well controlled without any specific ocular treatment. The patient demonstrated a prolonged progression-free survival.

Conclusion

This is the first report of a rare case with solitary ocular metastasis as the initial manifestation of lung squamous cell carcinoma. This rare patient was treated based on evidence-based medicine, indicating the importance of cooperation within an MDT. The successful treatment of this case was reported as a new therapeutic reference for clinicians who encounter similar cases in the future.

https://ift.tt/2Oz8KPY

Latissimus dorsi rotational flap combined with a custom-made scapular prosthesis after oncological surgical resection: a report of two patients

Abstract

Background

Sarcomas that arise from the scapula or periscapular soft tissues often require a total scapulectomy. This often implies a large complex tissue defect that needs adequate reconstruction of both bone and soft tissue. Although various methods have been developed, no optimal procedure has emerged. Postoperative complications are common and functional recovery is not always satisfactory. This study aims to present a new surgical technique that combines a custom-made scapular prosthesis with a functional latissimus dorsi flap.

Case presentation

Two patients diagnosed with malignant tumour of the scapular region were surgically treated after proper multidisciplinary evaluation. The first patient underwent the procedure as a first surgery, the second as revision surgery. The new technique comprises three surgical stages: excisional surgery with soft tissue resection and scapulectomy, bone reconstruction with custom-made prosthesis, and soft tissue reconstruction using a latissimus dorsi rotational flap overturned on the prosthesis. The goal is to set up a new functional unit combining an anatomically shaped implant (manufactured using latest three-dimensional printing technology) and a muscular flap, and to maintain the neurovascular supply. The patients were followed up to evaluate functional outcome and complications. Both patients were alive with no evidence of disease. Functional results were satisfactory and the Musculoskeletal Tumor Society scores were 87% and 63%, respectively. No surgical complications such as implant breakage, joint collapse, wound dehiscence, or infection were observed.

Conclusions

This new technique upgrades the role of the latissimus dorsi flap to a functional tool in combination with an anatomical, three-dimensionally printed, custom-made prosthesis, and provides adequate well-vascularized and healthy tissue to maximize the likelihood of successful limb salvage.

https://ift.tt/2NTYCfc

Human papillomavirus infection in patients with laryngeal carcinoma

Abstract

Background

The aim of this study was to determine the HPV positivity rate in patients with laryngeal cancer, and to determine the effect of HPV positivity on survival. An additional aim was to determine if patients with HPV positive laryngeal cancer are more sensitive to chemotherapy and if such sensitivity differs according to chemotherapy protocol.

Methods

The study included laryngeal specimens obtained from 82 laryngeal cancer patients and 11 laryngeal specimens with normal laryngeal mucosa that were obtained from our hospital's paraffin block archives between 1995 and 2013. HPV was detected via chromogenic in situ hybridization (cISH) and confirmed via genotyping.

Results

HPV was not detected in any of the 82 laryngeal cancer patients' laryngeal specimens, nor in any of the 11 archived laryngeal specimens with normal laryngeal mucosa via cISH. Genotyping confirmed these findings; none of the HPV types studied were detected in any of the specimens. As none of the study samples were HPV positive, it was not possible to compare survival, recurrence, or chemotherapy sensitivity.

Conclusions

HPV infection is not a leading cause of laryngeal cancer; however, additional research on HPV positivity in patients with laryngeal cancer and its effect on recurrence, survival, and chemotherapy sensitivity is warranted.

https://ift.tt/2OC4H56

Shear wave elastography in the evaluation of level VI lymph nodes in papillary thyroid carcinoma: combined with gray-scale ultrasound ex vivo

Abstract

Background

The evaluation of cervical lymph nodes is very important for patients with papillary thyroid carcinoma (PTC). Conventional ultrasound is recommended to assess the status of cervical lymph nodes but the diagnostic performance is not satisfying especially in level VI lymph nodes. Recently, shear wave elastography has shown great potential in diagnosis. Therefore, this study aimed at exploring the value of shear wave elastography in ultrasound evaluation for level VI lymph nodes in papillary thyroid carcinoma. Because Hashimoto's thyroiditis may influence the diagnostic performance, a subgroup was also analysed that included only lymph nodes from PTC without Hashimoto's thyroiditis.

Methods

Eighty-Seven level VI lymph nodes from 22 consecutive patients with papillary thyroid carcinoma were evaluated by gray-scale ultrasound and SWE in condition of ex vivo before rapid frozen section. Gray-scale ultrasound and shear wave elastography indexes of metastatic and non-metastatic lymph nodes were evaluated by statistical analysis separately in all patients and in patients without Hashimoto's thyroiditis. Indexes included long diameter, short diameter, short-to-long diameter ratio (S/L ratio), E_mean, E_min, E_max and E_SD. The rapid frozen section result of each lymph node was used as gold standard to evaluate the diagnostic performance of gray-scale ultrasound and combination method which combined gray-scale ultrasound and SWE.

Results

In all patients, significant indexes included short diameter (p = 0.009), S/L ratio (p = 0.003), E_max (p = 0.016) and E_SD (p = 0.006). In patients without Hashimoto's thyroiditis, significant indexes included short diameter (p = 0.002), S/L ratio (p = 0.003), E_mean (p = 0.030), E_max (p < 0.001) and E_SD (p = 0.001). Combining gray-scale ultrasound with SWE, combination method had higher AUC than gray-scale ultrasound both in all patients (0.887 vs 0.841) and patients without Hashimoto's thyroiditis (0.925 vs 0.866). Gray-scale ultrasound had higher AUC in patients without Hashimoto's thyroiditis than in all patients (0.866 vs 0.841), which was the same with combination method (0.925 vs 0.887).

Conclusion

Shear wave elastography can provide additional information for ultrasound evaluation of level VI lymph nodes in papillary thyroid carcinoma, especially in papillary thyroid carcinoma without Hashimoto's thyroiditis.

https://ift.tt/2NS91Ip

Fear of cancer recurrence trajectory during radiation treatment and follow-up into survivorship of patients with breast cancer

Abstract

Background

Fear of cancer recurrence (FCR) has been shown to be higher in patients treated with external beam radiotherapy (RT) compared to those untreated. However, little is known about the dynamics of patient's FCR during and after RT. The aim of this study was to examine FCR levels in a longitudinal panel design with breast cancer patients receiving RT.

Methods

Consecutive newly-diagnosed breast cancer patients (n = 94) attending a single cancer centre were invited to complete a 7-item FCR scale (FCR7) that was collected weekly by paper instrument and at a follow-up phone call 6–8 weeks after completion of RT. Descriptive statistics, and Latent Growth Curve Modelling (LGCM) were utilised to analyse the data.

Results

Women who were younger, single/separated, had chemotherapy, had extra boost radiation treatment, taking Herceptin and treated by 4-field technique reported higher recurrence fear at baseline. There was strong evidence of substantial variation in the trajectory of FCR (z = − 3.54, p < .0001). The average trajectory of FCR over RT was negative (unstandardized estimate = − 0.59) and associated with FCR follow-up level (standardised estimate = 0.36, z = 3.05, p < .002), independent of baseline recurrence fears.

Conclusion

Patients vary in their trajectory of recurrence fears over RT which predicts FCR approximately 2 months following treatment. Review appointments by therapy radiographers presents an opportunity to intervene in FCR trajectories.

Trial registration

ClinicalTrials.gov: NCT02599506. Prospectively registered on 11th March 2015.

https://ift.tt/2OAqJFx

Aberrant miRNAs expressed in HER-2 negative breast cancers patient

Abstract

Background

Breast cancer is a highly heterogeneous pathology, exhibiting a number of subtypes commonly associated with a poor outcome. Due to their high stability, microRNAs are often regarded as non-invasive cancer biomarkers, having an expression pattern specific for their 'cell of origin'.

Method

Triple negative breast cancer (TNBC: ER-, PR-, Her-2-) and double positive breast cancer (DPBC: ER+, PR+, Her-2) miRNA expression patterns were obtained by analysis of the TCGA (The Cancer Genome Atlas) data, followed by PCR-array analysis on plasma samples from 20 TNBC patients, 14 DPBC patients and 11 controls.

Results

Three downregulated and nine upregulated miRNAs were obtained from the TNBC analysis. Five overexpressed miRNAs were identified in the DPBC group. Four of the dysregulated miRNAs (miR-10a, miR-125b, miR-210 and miR-489) were common for both groups. The cluster miR-17-92 (miR-17, miR-20a, miR-20b, and miR-93), along with miR-130, miR-22 and miR-29a/c, were found to differentiate between TNBC and DPBC. A panel of five transcripts (miR-10a, miR-125, miR-193b, miR-200b and miR-489) was validated in a new set of plasma samples. The overlapping of TCGA and plasma profiling data revealed miR-200b, miR-200c, miR-210 and miR-29c as common signature. MiR-200b was validated on additional normal and tumor tissue samples. The expression level of this transcript from the TCGA data was correlated with lung and bone metastatic genes.

Conclusion

The miR-200b presents a great potential for the future advancements in the diagnostic/prognostic and therapeutic approach of TNBC, along with other coding or non-coding transcripts. However, this needs to be further integrated in a regulatory network that acts in conjunction with other markers that affect the patients' prognosis or response to therapy.

https://ift.tt/2NRMnzK

Amniotic membrane transplantation with or without autologous cultivated limbal stem cell transplantation for the management of partial limbal stem cell deficiency

https://ift.tt/2yqekd0

Pa. township considers implementing AED ordinance

The new ordinance would require building owners to put an automated external defibrillator in high-occupancy places

https://ift.tt/2AfyGXT

An unusual case report of indolent T-cell lymphoproliferative disorder with aberrant CD20 expression involving the gastrointestinal tract and bone marrow

Indolent T-cell proliferative disorder of the GIT is a rare and provisional entity in the revised WHO 2016 classification. The patients usually have prolonged survival with persistent disease even without any ...

https://ift.tt/2J6bXQO

Targeting metabolic flexibility via angiopoietin-like 4 protein sensitizes metastatic cancer cells to chemotherapy drugs

Abstract

Overcoming multidrug resistance has always been a major challenge in cancer treatment. Recent evidence suggested epithelial-mesenchymal transition plays a role in MDR, but the mechanism behind this link remains unclear. We found that the expression of multiple ABC transporters was elevated in concordance with an increased drug efflux in cancer cells during EMT. The metastasis-related angiopoietin-like 4 (ANGPTL4) elevates cellular ATP to transcriptionally upregulate ABC transporters expression via the Myc and NF-κB signaling pathways. ANGPTL4 deficiency reduced IC₅₀ of anti-tumor drugs and enhanced apoptosis of cancer cells. In vivo suppression of ANGPTL4 led to higher accumulation of cisplatin-DNA adducts in primary and metastasized tumors, and a reduced metastatic tumor load. ANGPTL4 empowered cancer cells metabolic flexibility during EMT, securing ample cellular energy that fuels multiple ABC transporters to confer EMT-mediated chemoresistance. It suggests that metabolic strategies aimed at suppressing ABC transporters along with energy deprivation of EMT cancer cells may overcome drug resistance.

https://ift.tt/2S4KC5R

Clindamycin suppresses virulence expression in inducible clindamycin-resistant Staphylococcus aureus strains

Clindamycin is a protein synthesis inhibitory agent that has the ability to suppress the expression of virulence factors in Staphylococcus aureus. Recent guidelines recommend the use of clindamycin for the treatm...

https://ift.tt/2J6UszP

Binocular coordination and reading performance during smartphone reading in intermittent exotropia

https://ift.tt/2CvSGat

Correlates of smoking status in cancer survivors

Abstract

Purpose

To determine the characteristics associated with cancer survivors which indicate continued cigarette smoking at or around the time of cancer diagnosis.

Methods

A total of 631 survivors were recruited in four cancer centers in Memphis, TN, between March 2015 and June 2016. To increase the probability of accurate reporting, surveys were conducted anonymously. A total of 112 respondents reported they were current smokers and 202 reported they were former smokers (n = 314), who comprised the sample.

Results

We found that the rate of daily e-cigarette use among cancer survivors who smoked was 15.2% versus 3.9% in cancer survivors who no longer smoked. The national rate of adult e-cigarette use is 3.5%. Multivariate models correlated the characteristics of current versus former smokers and revealed that increasing age (aOR = 0.97, p < .0001), decreasing education (aOR = 2.39, p < .02), and current use of e-cigarettes (aOR = 3.74, p < .00045) were frequently associated with current cigarette smoking.

Conclusions

While age and gender were associated with continued smoking, current use of e-cigarettes was associated with almost four times higher odds of being a current smoker. Further research is needed to determine if use of e-cigarettes deters or promotes the smoking cessation process, at least in cancer survivors.

Implications for Cancer Survivors

Among cancer survivors who continue to smoke after a cancer diagnosis, use of e-cigarettes is highly prevalent; research is needed to determine whether use of e-cigarettes promotes, has no effect, or hinders smoking cessation efforts among this vulnerable population.

https://ift.tt/2yqMY6D

Next-generation sequencing of prostate cancer: genomic and pathway alterations, potential actionability patterns, and relative rate of use of clinical-grade testing

.


https://ift.tt/2PHzqKE

Labor pain control by aromatherapy: A meta-analysis of randomized controlled trials

Publication date: Available online 19 October 2018

Source: Women and Birth

Author(s): Shuo-Fei Chen, Chia-Hui Wang, Pi-Tuan Chan, Hsiu-Wen Chiang, Tsung-Ming Hu, Ka-Wai Tam, El-Wui Loh

Abstract

Background

Aromatherapy is a treatment method that applies fragrant extracts from herbal plants, existed long ago in medical history as a major treatment approach and now used as an auxiliary treatment and sometimes a major treatment for pain and stress management, including those that occur in labor.

Aim

We aimed to conduct a meta-analysis of randomized controlled trials of the effectiveness of aromatherapy on labor pain and duration reduction.

Methods

We searched the Pubmed, EMBASE, Cochrane Central Register of Controlled Trials, Google Scholar and Clinicaltrials.gov for randomized controlled trials investigating the effectiveness of aromatherapy on labor pain and duration.

Results

A total of 17 trials with low-risk labor parturient women were included for meta-analysis using the Review Manager 5.3. Meta-analyses showed that aromatherapy reduced labor pain in the transition phase and the duration of active phase and third stage labor; a trend toward shortened duration was observed in the second stage. Also, aromatherapy had no influences on emergency caesarean section, membrane rupture, and spontaneous labor onset.

Conclusion

Our findings suggest that aromatherapy is effective in reducing labor pain and duration, and generally safe to the mothers. However, due to the heterogeneity across trials in some of the outcomes, further trials with device-based pain measurements, larger sample size, and more stringent design, should be conducted before strong recommendation.

https://ift.tt/2CvlP5B

Regimes of Complex Lipid Bilayer Phases Induced by Cholesterol Concentration in MD Simulation

Cholesterol is essential to the formation of phase separated lipid domains in membranes. Lipid domains can exist in different thermodynamic phases depending on the molecular composition, and play significant roles in determining structure and function of membrane proteins. We investigate the role of cholesterol in the structure and dynamics of ternary lipid mixtures displaying phase separation using Molecular Dynamics simulations, employing a physiologically-relevant span of cholesterol concentration.

https://ift.tt/2NRS7JX

Microtubule feedback and LET-99-dependent control of pulling forces ensure robust spindle position.

During asymmetric division of Caenorhabditis elegans zygote, to properly distribute cell fate determinants, the mitotic spindle is asymmetrically localized by a combination of centering and cortical pulling microtubule-mediated forces, the dynamics of the latter being regulated by mitotic progression. Here we show a novel and additional regulation of these forces by spindle position itself. For that, we observed the onset of transverse spindle oscillations which reflects the burst of anaphase pulling forces.

https://ift.tt/2q3F9zs

Steroidal alkaloids and conessine from the medicinal plant Holarrhena antidysenterica restore antibiotic efficacy in a Galleria mellonella model of multidrug-resistant Pseudomonas aeruginosa infection

This study aimed to evaluate the efficacy of combinations of steroidal alkaloids and conessine from the Thai medicinal plant Holarrhena antidysenterica with antibiotics against Pseudomonas aeruginosa strains poss...

https://ift.tt/2Pbf27P

Hexane extract from Spondias tuberosa (Anacardiaceae) leaves has antioxidant activity and is an anti-Candida agent by causing mitochondrial and lysosomal damages

Spondias tuberosa is a plant that produces a fruit crop with high economic relevance at Brazilian Caatinga. Its roots and leaves are used in folk medicine.

https://ift.tt/2EC8ElT

Free radical scavenging, α-glucosidase inhibitory and lipase inhibitory activities of eighteen Sudanese medicinal plants

Lifestyle-related diseases such as diabetes are steadily increasing worldwide. In Sudan, there are a variety of plant species used traditionally for the treatment of diabetes, obesity and other symptoms which ...

https://ift.tt/2P8nxR2

The leaves of Crataeva nurvala Buch-Ham. modulate locomotor and anxiety behaviors possibly through GABAergic system

Crataeva nurvala Buch-Hum is an indigenous herb, extensively used in traditional medicines of the South Asian countries to treat inflammation, rheumatic fever, gastric irritation, and constipation. Despite this w...

https://ift.tt/2ExBsMk

Complementary and alternative medicine use among persons with multiple chronic conditions: results from the 2012 National Health Interview Survey

Although a quarter of Americans are estimated to have multiple chronic conditions, information on the impact of chronic disease dyads and triads on use of complementary and alternative medicine (CAM) is scarce...

https://ift.tt/2Pa3qSA

The Influence of Globally Ungrammatical Local Syntactic Constraints on Real‐Time Sentence Comprehension: Evidence From the Visual World Paradigm and Reading

Cognitive Science, EarlyView.


https://ift.tt/2AkBgvY

Evaluation of microvascular changes in the macular area of eyes with rhegmatogenous retinal detachment without macular involvement using swept-source optical coherence tomography angiography

https://ift.tt/2Cu9gHG

No latency to dentate granule cell epileptogenesis in experimental temporal lobe epilepsy with hippocampal sclerosis

Epilepsia, EarlyView.


https://ift.tt/2q2FgLG

Epilepsy surgery in Panama: Establishment of a successful hybrid program as a model for small middle‐income countries

Epilepsia, EarlyView.


https://ift.tt/2R4znZU

Do Women in the Newsroom Make a Difference? Coverage Sentiment toward Women and Men as a Function of Newsroom Composition

Abstract

Positive or negative media coverage may have important consequences for individuals' lives and ability to succeed. One potential factor that may affect the tone of coverage, in particular for women, is the gender of newsroom managers. Some scholars have suggested that women in key editorial and managerial roles should have a positive effect on the overall coverage of issues in the news, and specifically on the coverage of women. We used fixed effects regression to analyze panel data on the coverage sentiment of 212 U.S. newspapers from various cities and states between 2004 and 2009 to examine the effects of the gendered composition of newsrooms on coverage tone for both men and women. Our results showed that individuals with female names receive more positive coverage than those with male names do in every section of the newspaper. We also found that increases in female representation on newspapers' editorial boards resulted in coverage for women that is moderately more positive. However, there is no evidence that under female executive editorship coverage sentiment favors women. Our findings are consistent with the work of gender sociologists and media scholars who have highlighted the media's rigid gender structures and their resistance to change.

https://ift.tt/2q0xKR9

Influence of novel implant selective laser melting framework design on mechanical durability of acrylic veneer

Clinical Implant Dentistry and Related Research, EarlyView.


https://ift.tt/2NRcqHl

Health care providers’ adherence to immediate postpartum care guideline and associated factors among women who gave birth in Mekele public teaching hospitals, Tigray 2018

To assess health care providers adherence to immediate postpartum care and associated factors among women's who gave birth in Mekele teaching public hospitals, 2018.

https://ift.tt/2EIAIUy

Exploring the role of obesity and overweight in predicting postoperative outcome of abdominal surgery in a sub-Saharan African setting: a prospective cohort study

Current literature on the role of excess weight in predicting surgical outcome is controversial. In sub-Saharan Africa, there is extreme paucity of data regarding this issue in spite of the increasing rates of...

https://ift.tt/2P8niFI

Prevalence, antimicrobial susceptibility profile and predictors of asymptomatic bacteriuria among pregnant women in Adigrat General Hospital, Northern Ethiopia

Approach to asymptomatic bacteriuria among pregnant women in Ethiopia is mainly based on clinical grounds and urine strip and microscopy tests. On top of this, the treatment is also on an empirical basis which...

https://ift.tt/2EIAE7g

Nigella sativa as an anti-inflammatory agent in asthma

Nigella sativa (N. sativa) has several pharmacological actions which include antioxidant, antidiabetic, anticancer, antitussive, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, and bron...

https://ift.tt/2Pddlqn

Balance of pro- and anti-inflammatory cytokines in livers of high fat diet rats exposed to fractionated gamma irradiation

In this work, the effects of irradiation and high fat diet (HFD) intake have been examined in Wistar rat livers. HFD Wistar rats were exposed three times per week for 2 months to three different doses (0.5, 1,...

https://ift.tt/2EzqwxV

Clearing the air: towards agreement about access to high cost cancer medicines

https://ift.tt/2PLlYWc

Axitinib Versus Placebo as an Adjuvant Treatment for Renal Cell Carcinoma: Results From the Phase III, Randomized ATLAS Trial

Abstract

Background

The ATLAS trial compared axitinib versus placebo in patients with locoregional renal cell carcinoma (RCC) at risk of recurrence after nephrectomy.

Patients and Methods

In a phase III, randomized, double-blind trial, patients had >50% clear-cell RCC, had undergone nephrectomy, and had no evidence of macroscopic residual or metastatic disease (independent review committee [IRC] confirmed). The intent-to-treat population included all randomized patients (≥pT2 and/or N+, any Fuhrman grade [FG], Eastern Cooperative Oncology Group status 0/1). Patients (stratified by risk group/country) received (1:1) oral twice-daily axitinib 5 mg or placebo for ≤3 years, with a 1-year minimum unless recurrence, occurrence of second primary malignancy, significant toxicity, or consent withdrawal. The primary end point was disease-free survival (DFS) per IRC. A prespecified DFS analysis in the highest-risk subpopulation (pT3, FG ≥ 3 or pT4 and/or N+, any T, any FG) was conducted.

Results

A total of 724 patients (363 versus 361, axitinib versus placebo) were randomized from May 8, 2012, to July 1, 2016. The trial was stopped due to futility at a preplanned interim analysis at 203 DFS events. There was no significant difference in DFS per IRC (hazard ratio [HR] = 0.870; 95% confidence interval [CI]: 0.660–1.147; P=0.3211). In the highest-risk subpopulation, a 36% and 27% reduction in risk of a DFS event (HR; 95% CI) was observed per investigator (0.641; 0.468–0.879; P=0.0051), and by IRC (0.735; 0.525–1.028; P=0.0704), respectively. Overall survival data were not mature. Similar adverse events (AEs; 99% versus 92%) and serious AEs (19% versus 14%), but more grade 3/4 AEs (61% versus 30%) were reported for axitinib versus placebo.

Conclusions

ATLAS did not meet its primary end point; however, improvement in DFS per investigator was seen in the highest-risk subpopulation. No new safety signals were reported.

Trial registration number

NCT01599754

https://ift.tt/2PfYVpk

Biomarker analysis beyond angiogenesis: RAS/RAF mutation status, tumour sidedness, and second-line ramucirumab efficacy in patients with metastatic colorectal carcinoma from RAISE, a global phase 3 study

Abstract

Background

Second-line treatment with ramucirumab+FOLFIRI improved overall survival (OS) versus placebo+FOLFIRI for patients with metastatic colorectal carcinoma (mCRC) (hazard ratio [HR]=0.84, 95%CI=0.73–0.98, P=0.022). Post-hoc analyses of RAISE patient data examined the association of RAS/RAF mutation status and the anatomical location of the primary CRC tumour (left versus right) with efficacy parameters.

Patients and methods

Patient tumour tissue was classified as BRAF mutant, KRAS/NRAS ("RAS") mutant, or RAS/BRAF wild-type. Left-CRC was defined as the splenic flexure, descending and sigmoid colon, and rectum; right-CRC included transverse, ascending colon and cecum.

Results

RAS/RAF mutation status was available for 85% of patients (912/1072) and primary tumour location was known for 94.4% of patients (1012/1072). A favourable and comparable ramucirumab treatment effect was observed for patients with RAS mutations (OS HR = 0.86, 95% CI = 0.71–1.04) and patients with RAS/BRAF wild-type tumours (OS HR = 0.86, 95% CI = 0.64–1.14). Among the 41 patients with BRAF-mutated tumours, the ramucirumab benefit was more notable (OS HR = 0.54, 95% CI = 0.25–1.13), although, as with the other genetic subgroup analyses, differences were not statistically significant. Progression-free survival (PFS) data followed the same trend. Treatment-by-mutation status interaction tests (OS P=0.523, PFS P=0.655) indicated that the ramucirumab benefit was not statistically different among the mutation subgroups, although the small sample size of the BRAF group limited the analysis. Addition of ramucirumab to FOLFIRI improved left-CRC median OS by 2.5 month over placebo (HR = 0.81, 95% CI = 0.68–0.97); median OS for ramucirumab-treated patients with right-CRC was 1.1 month over placebo (HR = 0.97, 95% CI = 0.75–1.26). The treatment-by-subgroup interaction was not statistically significant for tumour sidedness (P = 0.276).

Conclusions

In the RAISE study, the addition of ramucirumab to FOLFIRI improved patient outcomes, regardless of RAS/RAF mutation status and tumour sidedness. Ramucirumab treatment provided a numerically substantial benefit in BRAF-mutated tumours, although the p-values were not statistically significant. ClinicalTrials.gov, NCT01183780

https://ift.tt/2Paqh03

Nanoscale Extracellular Vesicle-Derived DNA is Superior to Circulating Cell Free DNA for Mutation Detection in Early-Stage Non-Small Cell Lung Cancer

Abstract

Background

The comparison between relatively intact nanoscale extracellular vesicle derived DNA (nEV-DNA) and fragmented circulating cell free DNA (cfDNA) in mutation detection among patients with non-small cell lung cancer (NSCLC) has not been performed yet, and thus deserves investigation.

Patients and methods

Both nEV-DNA and cfDNA was obtained from 377 NSCLC patients with known EGFR mutation status and 69 controls. The respective EGFR^{E19del/T790M/L858R} mutation status was interrogated with amplification-refractory-mutation-system-based PCR assays (ARMS-PCR).

Results

Neither nEV-DNA nor cfDNA levels show a strong correlation with tumor volumes. There is no correlation between cfDNA and nEV-DNA levels either. The detection sensitivity of nEV-DNA and cfDNA using ARMS-PCR in early-stage NSCLC was 25.7% and 14.2%, respectively, with 96.6% and 91.7% specificity, respectively. In late-stage NSCLC, both nEV-DNA and cfDNA show ∼80% sensitivity and over 95% specificity.

Conclusions

nEV-DNA is superior to cfDNA for mutation detection in early-stage NSCLC using ARMS-PCR. However, the advantages vanish in late-stage NSCLC.

https://ift.tt/2PIcYRz

Identification of a novel crizotinib-sensitive MET-ATXN7L1 gene fusion variant in lung adenocarcinoma by next generation sequencing

https://ift.tt/2P6HXdd

Niacinamide and 12‐hydroxystearic acid prevented benzo(a)pyrene and squalene peroxides induced hyperpigmentation in skin equivalent

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2S14TJz

Expression of Proton‐sensing G‐Protein‐coupled receptors in selected skin tumors

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2yPuJav

On the relevance of an in vitro reconstructed human epidermis model for drug screening in atopic dermatitis

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2S3Ez1m

Two‐Layered and Stretchable e‐Textile Patches for Wearable Healthcare Electronics

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2EIyK6C

Clues to recognition of fumarate hydratase‐deficient renal cell carcinoma: Findings from cytologic and limited biopsy samples

Cancer Cytopathology, EarlyView.


https://ift.tt/2OE9Mu4

NIFTP revised: Chronicle of a change foretold

Cancer Cytopathology, EarlyView.


https://ift.tt/2NNudPO

Automated detection of cancer cells in effusion specimens by DNA karyometry

Cancer Cytopathology, EarlyView.


https://ift.tt/2OA2gQH

Variational based smoke removal in laparoscopic images

In laparoscopic surgery, image quality can be severely degraded by surgical smoke, which not only introduces errors for the image processing algorithms (used in image guided surgery), but also reduces the visi...

https://ift.tt/2R3j1Ay

Evaluation of spatial distribution and characterization of wall shear stress in carotid sinus based on two-dimensional color Doppler imaging

This study aims to use a wall shear stress (WSS) quantitative analysis software to analyze and evaluate the carotid sinus WSS spatial distribution and characteristics in intima-media thickness (IMT) normal and...

https://ift.tt/2q2buq5

Fine-grain recordings of the electrically evoked compound action potential amplitude growth function in cochlear implant recipients

In cochlear implants (CI) measuring the electrically evoked compound action potential (ECAP) has become an important tool for verifying the electrode-nerve interface as well as establishing a basis for a map t...

https://ift.tt/2R3iXki

Social media and clinical trials: The pros and cons gain context when the patient is at the center

Cancer, EarlyView.


https://ift.tt/2ySM2r1

Surviving a transfixing gunshot wound to the head 70 years ago

Abstract

Surviving a gunshot wound to the head is a rare event, particularly in the past when medical treatment was much less advanced than it is today. Moreover, the finding of such a case as an identified specimen within a museum collection is even more uncommon. This led us to report on this unique case in this paper as it poses a challenge to forensic anthropology and provides a unique educational oppourtunity. The skull from the Collection at the Cranium Museum in the Department of Morphology and Genetic at the Federal University of São Paulo (UNIFESP) dates back to 1946. For trauma registration the bone location, severity, trauma aetiology, trauma classification, description, callus formation, periosteal reaction, degree and success of repair, and an estimate of the time elapsed since the trauma, were all assessed. To explore the case radiologically a CT scan of the skull was performed. Considering the survival of the patient and the morphology of the wound it is likely that the injury was caused by a small calibre, low-velocity gunshot. The bullet path shows an almost vertical direction on the right side of the individual's splanchno and neurocranium. The path of the projectile is consistent with a suicide attempt, although the possibility of a homicide simulating a suicide cannot be discarded. This case highlights how informative such cases can be to the practice of forensic anthropology.

https://ift.tt/2R4DoNS

Task errors contribute to implicit aftereffects in sensorimotor adaptation

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.


https://ift.tt/2ypwWKv

Purinergic modulation of neuronal activity in the rat prepositus hypoglossi nucleus

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.


https://ift.tt/2J8D9hU

The Power of the Parkinson's Patient According to Tom Isaacs: A Call to Action

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.


https://ift.tt/2yonTJO

Pedunculopontine Tegmentum Cholinergic Loss Leads to a Progressive Decline in Motor Abilities and Neuropathological Changes Resembling Progressive Supranuclear Palsy

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.


https://ift.tt/2J8eGt1

Liraglutide, sitagliptin and insulin glargine added to metformin: the effect on body weight and intrahepatic lipid in patients with type 2 diabetes mellitus and NAFLD

Hepatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2R3gEOa

A model for Glomerular filtration Rate Assessment In Liver disease (GRAIL) in the presence of renal dysfunction

Hepatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2q2C6HN

Plasma extracellular nanovesicle (exosome) derived biomarkers for drug metabolism pathways: A novel approach to characterise variability in drug exposure

British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2S3MyLC

Prevalence and incidence of prescription opioid analgesic use in Australia

British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2yOPLGa

Endoscopic Submucosal Dissection under D‐sorbitol Solution in Animal Model

Digestive Endoscopy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2q3VXGs

Stability and in vitro digestibility of beta‐carotene in nanoemulsions fabricated with different carrier oils

Food Science &Nutrition, EarlyView.


https://ift.tt/2R2ANDV

Evaluation of physicochemical properties and enzymatic activity of organic substrates during four crop cycles in soilless containers

Food Science &Nutrition, EarlyView.


https://ift.tt/2q3DLNe

A BAP31 intrabody induces gastric cancer cell death by inhibiting p27kip1 proteasome degradation

International Journal of Cancer, Volume 0, Issue ja, -Not available-.


https://ift.tt/2R2ANnp

Circulating exosomal non‐coding RNAs as prognostic biomarkers in human hepatocellular carcinoma

International Journal of Cancer, Volume 0, Issue ja, -Not available-.


https://ift.tt/2q05zls

Issue Information

International Journal of Cancer, Volume 143, Issue 9, Page 2085-2091, 1 November 2018.


https://ift.tt/2R36XiS

Issue Information

International Journal of Cancer, Volume 143, Issue 9, Page 2331-2332, 1 November 2018.


https://ift.tt/2pZQkJi

Cholesterol crystals in periapical lesions of root filled teeth

International Endodontic Journal, Volume 0, Issue ja, -Not available-.


https://ift.tt/2yME0jC

Microguided endodontics: A case report of a maxilary lateral incisor with pulp canal obliteration and apical periodontitis

International Endodontic Journal, Volume 0, Issue ja, -Not available-.


https://ift.tt/2ypvAzp