Western Blot-Based Logistic Regression Model for the Identification of Recent HIV-1 Infection: A Promising HIV-1 Surveillance Approach for Resource-Limited Regions

Objectives. Identifying recent infections is necessary to monitor HIV/AIDS epidemic; however, it needs to be further developed. Methods and Results. Participants were defined as having recent infection or older infection according to the estimated duration of HIV-1 infection and further assigned into training set and validation set according to their entering time points. Western blot (WB) confirmatory test and BED-CEIA were performed. The performance of the two methods on recent HIV-1 diagnosis was evaluated and compared. 81 subjects were enrolled in the training set and 72 in the validation set. Relative grey ratios of p24, p39, p31, p66, gp41, and gp160 were significantly higher in older infected patients of the training set. The present status of p55 was more frequently missing in recently infected patients in both sets. The logistic stepwise regression analysis of WB method shows sensitivity, specificity, and accuracy of 93.02%, 92.11%, and 92.59%. For BED-CEIA, they were 76.74%, 86.84%, and 81.48%. In the validation set, overall agreement rate, sensitivity, and specificity were 88.46%, 84.78%, and 86.11% in the WB-based method and 50.00%, 84.78%, and 72.22% in the BED-CEIA method. Conclusions. WB-based method is a promising approach to predict recent HIV-1 infection, especially in resource-limited regions.

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Model Analysis of Digital Models in Moderate to Severe Crowding: In Vivo Validation and Clinical Application

Objective. We investigated the suitability of intraoral-scan models for measuring tooth dimensions and the amount of crowding in patients with severe tooth crowding. Materials and Methods. Fifty-eight patients who had undergone intraoral scans for diagnosis were included. Cast models were divided into two groups depending on the amount of crowding, as determined by initial caliper-based measurements (mild crowding [MC] group: 4.5 mm). Twenty maxillary models and 20 mandibular models were used in this study. For the three types of models (i.e., IS digital model, C cast model, and CS digital model), the reproducibility and the precision of linear measurements were evaluated. Results. We found that linear measurements made using digital calipers on a plaster model and on the relevant software were reproducible. There was no significant difference in most linear measurements between digital models and the C model. There were differences in the amount of crowding (), although these were not clinically significant. There was no relationship between the precision of crowding in the three types of models and the severity of crowding. Conclusions. Digital models can be used for measuring crowding in both mild and severe crowding cases. However, crowding measured by digital models tends to be lesser than that measured by cast models, and this should be considered during clinical application.

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Simultaneous Quantification of Gallic Acid, Bergenin, Epicatechin, Epicatechin Gallate, Isoquercitrin, and Quercetin-3-Rhamnoside in Rat Plasma by LC-MS/MS Method and Its Application to Pharmacokinetics after Oral Administration of Ardisia japonica Extract

Ardisia japonica is a well-known traditional Chinese medicinal herb used as a diuretic, for treating cough and for stopping uterine bleeding. A simple, sensitive, and reliable LC-MS/MS method was developed to determine six active compounds in rat plasma and this method was further applied to the pharmacokinetic study of these compounds after oral administration of Ardisia japonica extract. Acetonitrile was used to precipitate the protein in the plasma samples. Using acetonitrile and formic acid aqueous solution (0.05%) as the mobile phase, the separation of the six compounds and internal standards was achieved at a flow rate of 300 μL min−1 on an Eclipse plus C18 column at an elution time of 16 min. A tandem mass spectrometer having an electrospray ionization (ESI) source was used in the detection of the analytes and internal standards using multiple reactions monitoring (MRM) in the negative ionization mode. The LLOQ was 2, 2, 4, 2, 1, and 0.4 ng mL−1 for gallic acid, bergenin, epicatechin, epicatechin gallate, isoquercitrin, and quercetin-3-rhamnoside, respectively. The validated method was applied to the pharmacokinetic study of gallic acid, bergenin, and quercetin-3-rhamnoside in rat plasma after oral administration of A. japonica extract to rats.

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Retracted: Antioxidant Activity and Characterization of One New Polysaccharide Obtained from Perigord Truffle (Tuber huidongense)

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Recording Brain Electromagnetic Activity During the Administration of the Gaseous Anesthetic Agents Xenon and Nitrous Oxide in Healthy Volunteers

Simultaneous magnetoencephalography and electroencephalography provides a useful tool to search for common and distinct macro-scale mechanisms of reductions in consciousness induced by different anesthetics. This paper illustrates the empirical methods underlying the recording of such data from healthy humans during N-Methyl-D-Aspartate-(NMDA)-receptor-antagonist-based anesthesia during inhalation of nitrous oxide and xenon.

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Kbtbd2 inhibits the cytotoxic activity of immortalized NK cells through down-regulating mTOR signaling in a mouse hepatocellular carcinoma model

Abstract

Natural killer cell (NK cell)-based immunotherapy is a promising therapeutic strategy for hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the regulation of NK cell function in the tumor sites are not completely elucidated. In this study, we identified the enhanced expression of kelch repeat and BTB (POZ) domain containing 2 (Kbtbd2) in intratumoral NK cells in a mouse HCC implantation model as a negative regulator of NK cells. To investigate this interaction,, we used a Tet-on inducible expression system to control Kbtbd2 expression in an immortalized mouse NK cell line KIL C.2. With this approach, we found that overexpression of Kbtbd2 reduced KIL C.2 cell proliferation, decreased expression certain of Ly49 receptor family members, and substantially impaired cytotoxic activity of KIL C.2 cells in vitro. Moreover, phosphorylation of mTOR and its target 4E-binding protein 1 was reduced in Kbtbd2-expressing KIL C.2 cells, along with down-regulated phosphorylation of Erk1/2. Adoptively transferred Kbtbd2-expressing KIL C.2 cells exhibited weaker tumoricidal effect on hepatocellular carcinoma cells in the HCC implantation model, in comparison with transferred control KIL C.2 cells. Taken together, our investigation indicates that Kbtbd2 is an inhibitory molecule for the tumoricidal activity of KIL C.2 cells and perhaps intratumoral NK cells.

This article is protected by copyright. All rights reserved

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Dissection and Explant Culture of Murine Allantois for the In Vitro Analysis of Allantoic Attachment

We describe an in vitro assay to model chorioallantoic attachment, the first step in placenta formation. The protocol demonstrates the dissection and explant culture of murine allantoides on immobilized α4β1 integrin. Allantois attachment is evaluated microscopically at pre-determined time points.

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Management of patients on antithrombotic agents undergoing emergency and elective endoscopy: joint Asian Pacific Association of Gastroenterology (APAGE) and Asian Pacific Society for Digestive Endoscopy (APSDE) practice guidelines

This Guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society for Digestive Endoscopy (APSDE). It was developed in response to the increasing use of antithrombotic agents (antiplatelet agents and anticoagulants) in patients undergoing gastrointestinal (GI) endoscopy in Asia. After reviewing current practice guidelines in Europe and the USA, the joint committee identified unmet needs, noticed inconsistencies, raised doubts about certain recommendations and recognised significant discrepancies in clinical practice between different regions. We developed this joint official statement based on a systematic review of the literature, critical appraisal of existing guidelines and expert consensus using a two-stage modified Delphi process. This joint APAGE-APSDE Practice Guideline is intended to be an educational tool that assists clinicians in improving care for patients on antithrombotics who require emergency or elective GI endoscopy in the Asian Pacific region.

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Response to: 'Prognosis of immune-tolerant phase chronic hepatitis B by Chu and Liaw

We appreciate the interest given to our article1 by Chu and Liaw.2

Determining disease phases of patients with chronic hepatitis B (CHB) is essential for assessing patient prognosis and need for treatment. Distinguishing between the immune-tolerant and immune-active phases among patients with hepatitis B e antigen (HBeAg)-positive CHB is best determined by identifying significant necroinflammation and/or fibrosis through liver biopsy. However, given the dynamic nature of CHB and the risks and costs of repeated liver biopsy, this recommendation may not always be realistic, especially in regions with high CHB prevalence.

Current practice guidelines recommend considering HBeAg positivity and serum levels of HBV DNA and alanine aminotransferase (ALT) to determine the phases of CHB, and ALT levels are a crucial criterion for determining treatment initiation in patients with CHB. However, the HBV DNA cut-off levels for the immune-tolerant phase vary among guidelines. More importantly, as observed in our study,...

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Modern management of perianal fistulas in Crohns disease: future directions

Perianal fistulae in patients with Crohn's disease (CD) can be associated with significant morbidity resulting in negative impact on quality of life. The last two decades have seen significant advancements in the management of perianal fistulas in CD, which has evolved into a multidisciplinary approach that includes gastroenterologists, colorectal surgeons, endoscopists and radiologists. Despite the introduction of new medical therapies such as antitumour necrosis factor and novel models of care delivery, the best fistula healing rates reported with combined medical and surgical approaches are approximately 50%. More recently, newer biologics, cell-based therapies as well as novel endoscopic and surgical techniques have been introduced raising new hopes that outcomes can be improved upon. In this review, we describe the modern management and the most recent advances in the management of complex perianal fistulising CD, which will likely impact clinical practice. We will explore optimal use of both older and newer biological agents, as well as new data on cell-based therapies. In addition, new techniques in endoscopic and surgical approaches will be discussed.

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Liver sampling: a vital window into HBV pathogenesis on the path to functional cure

In order to optimally refine the multiple emerging drug targets for hepatitis B virus (HBV), it is vital to evaluate virological and immunological changes at the site of infection. Traditionally liver biopsy has been the mainstay of HBV disease assessment, but with the emergence of non-invasive markers of liver fibrosis, there has been a move away from tissue sampling. Here we argue that liver biopsy remains an important tool, not only for the clinical assessment of HBV but also for research progress and evaluation of novel agents. The importance of liver sampling has been underscored by recent findings of specialised subsets of tissue-resident immune subsets capable of efficient pathogen surveillance, compartmentalised in the liver and not sampled in the blood. Importantly, the assessment of virological parameters, such as cccDNA quantitation, also requires access to liver tissue. We discuss strategies to maximise information obtained from the site of infection and disease pathology. Fine needle aspirates of the liver may allow longitudinal sampling of the local virus/host landscape. The careful utilisation of liver tissue and aspirates in conjunction with blood will provide critical information in the assessment of new therapeutics for the functional cure of HBV.

http://ift.tt/2r03LMJ

Risk factors for gastric cancer: is it time to discard PPIs?

We read with great interest the paper by Cheung et al recently published in your journal.1 The extensive worldwide use of proton pump inhibitors (PPIs) makes the debate about a related risk of gastric cancer a very popular and current topic.2 Potentially, the PPI-induced reduction of acid content in the stomach may contribute to gastric cancer pathogenesis, possibly by increasing gastrin secretion, with a resultant constant trophic stimulus on the gastric mucosa, similar to Helicobacter pylori-related chronic atrophic gastritis.3 These conditions may both feasibly share a similar alteration of the gastric microbiota.4

However, evidence on this topic is not definitive: two meta-analyses of randomised controlled trials found no correlation between gastric cancer and long-term PPI use,5 6 whereas a meta-analysis of observational studies found a 40% increased risk associated with PPI use,7 similar to that of a recent...

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Sucrase-isomaltase 15Phe IBS risk variant in relation to dietary carbohydrates and faecal microbiota composition

Recently in Gut, a coding sucrase-isomaltase (SI) variant (15Phe at single nucleotide polymorphism rs9290264) with 35% reduced disaccharidase activity was reported to increase IBS risk and to correlate with more frequent stools. These observations were not assessed in relation to key dietary factors including carbohydrate (ie, SI substrates) consumption.1

Here, we studied two large German population-based cross-sectional cohorts, namely PopGen (n=639; average age 61.4; 44.8% female) and FoCus (n=759; average age 53.0; 58.5% female), with available genotype (genome-wide arrays), dietary (12-month food frequency questionnaire, FFQ), faecal microbiota (16S sequencing) and IBS status (self-reported from questionnaire) data, as previously described in detail.2–4

In a combined age/sex/body mass index (BMI)-adjusted logistic regression analysis of the two data sets, carriers of the 15Phe variant (52.86%) reported IBS significantly more often than non-carriers (3.69% vs 1.84%, respectively; P=0.044, OR=2.04), thus replicating and extending previous findings.1 When...

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Early changes in the pharmacokinetic profile of vedolizumab-treated patients with IBD may predict response after dose optimisation

We read with interest the recent paper by Colombel et al1 showing that vedolizumab is frequently used for patients with inflammatory bowel disease (IBD). There is evidence for an exposure–efficacy relationship for vedolizumab induction therapy.2 Increasing dosing frequency of vedolizumab to every 4 weeks leads to an improvement in clinical response in both ulcerative colitis (UC)3 and Crohn's disease (CD).4 In contrast to anti-tumour necrosis factor (TNF) agents, the correlation between the response to dose optimisation and changes in the pharmacokinetic profile of vedolizumab-treated patients remains unknown. We performed a retrospective analysis of all vedolizumab-treated patients that increased dosing frequency because of primary non-response (≤week 14 after treatment initiation) or secondary loss of response (>week 14 after treatment initiation) in our tertiary referral IBD centre (Nancy University Hospital) between 1 April 2016 and 31 May 2017. Treatment response, defined as an improvement in clinical...

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Primary Biliary Cholangitis, DNA and Beyond: The Relative Contribution of Genes

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Deep grey matter volume loss drives disability worsening in multiple sclerosis

Abstract

Objective: Grey matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS.

Methods: We analysed 3,604 brain high-resolution T1-weighted MRI scans from 1,417 participants: 1,214 MS patients (253 clinically-isolated syndrome[CIS], 708 relapsing-remitting[RRMS], 128 secondary-progressive[SPMS], 125 primary-progressive[PPMS]), over an average follow-up of 2.41 years (standard deviation[SD]=1.97), and 203 healthy controls (HCs) [average follow-up=1.83 year, SD=1.77], attending 7 European centres. Disability was assessed with the Expanded-Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem and cerebral white matter. Hierarchical mixed-models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time-to-EDSS progression.

Results: SPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to-EDSS progression (hazard ratio=0.73, 95% CIs 0.65, 0.82; p<0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow-up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (-1.45%), PPMS (-1.66%), and RRMS (-1.34%) than CIS (-0.88%) and HCs (-0.94%)[p<0.01]. The rate of temporal GM atrophy in SPMS (-1.21%) was significantly faster than RRMS (-0.76%), CIS (-0.75%), and HCs (-0.51%). Similarly, the rate of parietal GM atrophy in SPMS (-1.24-%) was faster than CIS (-0.63%) and HCs (-0.23%) (all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta=0.04, p<0.001).

Interpretation: This large multi-centre and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions. This article is protected by copyright. All rights reserved.

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Mechanistic target of rapamycin complex 1 and 2 in human temporal lobe epilepsy

ABSTRACT

Objective: Temporal lobe epilepsy (TLE) is a chronic epilepsy syndrome defined by seizures and progressive neurological disabilities, including cognitive impairments, anxiety and depression. Here, human TLE specimens were investigated focusing on the mechanistic target of rapamycin (mTOR) Complex 1 (mTORC1) and Complex 2 (mTORC2) activities in the brain, as both pathways may represent unique targets for treatment.

Methods: Surgically resected hippocampal and temporal lobe samples from therapy-resistant TLE patients were analyzed by Western blotting to quantify the expression of established mTORC1 and mTORC2 activity markers and upstream or downstream signaling pathways involving the two complexes. Histological and immunohistochemical techniques were used to assess hippocampal and neocortical structural abnormalities and cell-specific expression of individual biomarkers. Samples from patients with focal cortical dysplasia (FCD) type II served as positive controls.

Results: We found significantly increased expression of phospho-mTOR (Ser2448), phospho-S6 (Ser235/236), phospho-S6 (Ser240/244) and phospho-Akt (Ser473) in TLE samples compared to controls, consistent with activation of both mTORC1 and mTORC2. Our work identified the PI3K and Ras/ERK signaling pathways as potential mTORC1 and mTORC2 upstream activators. In addition, we found that overactive mTORC2 signaling was accompanied by induction of two Akt-dependent pro-survival pathways, as evidenced by increased inhibitory phosphorylation of FoxO3a (Ser253) and GSK-β (Ser9).

Interpretation: Our data demonstrate that mTOR signaling is significantly dysregulated in human TLE, offering new targets for pharmacologic interventions. Specifically, clinically available drugs that suppress mTORC1 without compromising mTOR2 signaling, such as rapamycin and its analogs, may represent a new group of antiepileptogenic agents in TLE patients. This article is protected by copyright. All rights reserved.

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Cerebrospinal fluid macrophage biomarkers in amyotrophic lateral sclerosis

Abstract

Objective

The neurodegenerative disease amyotrophic lateral sclerosis (ALS) is a heterogeneous clinical syndrome involving multiple molecular pathways. The development of biomarkers for use in therapeutic trials is a priority. We sought to use a high-throughput proteomic method to identify novel biomarkers in individual cerebrospinal fluid samples.

Methods

Liquid chromatography-tandem mass spectrometry with label-free quantification was used to identify cerebrospinal fluid proteins using samples from a well-characterised longitudinal cohort comprising patients with ALS (n=43), the upper motor neuron variant primary lateral sclerosis (PLS, n=6), cross-sectional healthy (n=20) and disease controls (Parkinsons's n=20, ALS mimic disorders n=12).

Results

Three macrophage-derived chitinases showed increased abundance in ALS: chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1) and chitinase-3-like protein 2 (CHI3L2). Elevated CHI3L1 was common to ALS and PLS, whereas CHIT1 and CHI3L2 levels differed. Chitinase levels correlated with disease progression rate (CHIT1 r=0.56, p<0.001; CHI3L1 r=0.31, p=0.028; CHI3L2 r=0.29, p=0.044). CHIT1, CHI3L1 and CHI3L2 levels correlated with phosphorylated neurofilament heavy chain (pNFH; r=0.62, p<0.001; r=0.49, p<0.001; r=0.41, p<0.001). CHI3L1 levels, but not CHIT1 or CHI3L2, increased over time in those with low initial levels (gradient=0.005 log abundance units/month, p=0.001). High CHIT1 was associated with shortened survival (HR 2.84, p=0.009). Inclusion of pNFH in survival models left only an association of pNFH and survival (HR 1.26, p=0.019).

Interpretation

Neuroinflammatory mechanisms have been consistently implicated through various experimental paradigms. These results support a key role for macrophage activity in ALS pathogenesis, offering novel target engagement and pharmacodynamic biomarkers for neuroinflammation-focused ALS therapy. This article is protected by copyright. All rights reserved.

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Terminal spreading depolarization and electric silence in death of human cortex

Abstract

Objective: Restoring the circulation is the primary goal in emergency treatment of cerebral ischemia. However, better understanding of how the brain responds to energy depletion could inform the time available for resuscitation until irreversible damage and advance development of interventions that prolong this span. Experimentally, injury to central neurons begins only with anoxic depolarization. This potentially reversible, spreading wave typically starts 2-5 min after the onset of severe ischemia, marking the onset of a toxic intraneuronal change that eventually results in irreversible injury.

Methods: To investigate this in the human brain, we performed recordings with either subdural electrode strips (n=4) or intraparenchymal electrode arrays (n=5) in patients with devastating brain injury that resulted in activation of a Do Not Resuscitate-Comfort Care order followed by terminal extubation.

Results: Withdrawal of life-sustaining therapies produced a decline in brain tissue partial pressure of oxygen (p_tiO₂) and circulatory arrest. Silencing of spontaneous electrical activity developed simultaneously across regional electrode arrays in eight patients. This silencing, termed 'nonspreading depression', developed during the steep falling phase of p_tiO₂ (intraparenchymal sensor, n=6) at 11 (7, 14) mmHg. Terminal spreading depolarizations started to propagate between electrodes 3.9 (2.6, 6.3) min after onset of the final drop in perfusion and 13 to 266s after nonspreading depression. In one patient, terminal spreading depolarization induced the initial electrocerebral silence in a spreading depression pattern; circulatory arrest developed thereafter.

Interpretation: These results provide fundamental insight into the neurobiology of dying and have important implications for survivable cerebral ischemic insults. This article is protected by copyright. All rights reserved.

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Cellular membrane trafficking machineries utilized by the hepatitis viruses

Abstract

While the life cycles of hepatitis viruses (hepatitis A, B, C, D, and E viruses) have been modestly characterized, recent intensive studies have provided new insights. Because these viruses 'hijack' the membrane trafficking of the host cell machinery during replicative propagation, it is essential to determine and understand these specific cellular pathways. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are well known as a leading cause of liver cirrhosis and hepatocellular carcinoma. While substantial inroads toward treating HCV patients have recently been made, patients with HBV continue to require life-long treatment, which makes a thorough understanding of the HBV life cycle essential. Importantly, these viruses have been observed to "hijack" the secretory and endocytic membrane trafficking machineries of the hepatocyte. These can include the canonical clathrin-mediated endocytic process that internalizes virus through cell surface receptors. While these receptors are encoded by the host genome for normal hepatocellular functions, they also exhibit viral-specific recognition. Further, functions provided by the multivesicular body (MVB), that include endosomal sorting complexes required for transport (ESCRT), are now known to envelope a variety of different hepatitis viruses. In this review, we summarize the recent findings regarding the cellular membrane trafficking machineries utilized by HBV in the context of other hepatitis viruses. This article is protected by copyright. All rights reserved.

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A fixed partial EMT triggers carcinogenesis, whereas asymmetrical division of hybrid EMT cells drives cancer progression

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Hepatic PPARα function is controlled by polyubiquitination and proteasome-mediated degradation via the coordinated actions of PAQR3 and HUWE1

Abstract

Peroxisome proliferator-activated receptor α (PPARα) is a key transcriptional factor that regulates hepatic lipid catabolism by stimulating fatty acid oxidation and ketogenesis in an adaptive response to nutrient starvation. However, how PPARα is regulated by post-translational modification is poorly understood. Here, we identified that PAQR3 promotes PPARα ubiquitination through the E3 ubiquitin ligase HUWE1, thereby negatively modulating PPARα functions both in vitro and in vivo. Adenovirus-mediated Paqr3 knockdown and liver-specific deletion of the Paqr3 gene reduced hepatic triglyceride levels while increasing fatty acid oxidation and ketogenesis upon fasting. PAQR3 deficiency enhances the fasting-induced expression of PPARα target genes, including those involved in fatty acid oxidation and FGF21, a key molecule that mediates the metabolism-modulating effects of PPARα. PAQR3 directly interacts with PPARα and increases the polyubiquitination and proteasome-mediated degradation of PPARα. Furthermore, the E3 ubiquitin ligase HUWE1 was identified to mediate PPARα polyubiquitination. Additionally, PAQR3 enhances the interaction between HUWE1 and PPARα. Collectively, this study revealed that ubiquitination modification through the coordinated action of PAQR3 with HUWE1 plays a crucial role in regulating the activity of PPARα in response to starvation. This article is protected by copyright. All rights reserved.

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Selective IKK2 inhibitor IMD0354 disrupts NF-κB signaling to suppress corneal inflammation and angiogenesis

Abstract

Corneal neovascularization is a sight-threatening condition caused by angiogenesis in the normally avascular cornea. Neovascularization of the cornea is often associated with an inflammatory response, thus targeting VEGF-A alone yields only a limited efficacy. The NF-κB signaling pathway plays important roles in inflammation and angiogenesis. Here, we study consequences of the inhibition of NF-κB activation through selective blockade of the IKK complex IκB kinase β (IKK2) using the compound IMD0354, focusing on the effects of inflammation and pathological angiogenesis in the cornea. In vitro, IMD0354 treatment diminished HUVEC migration and tube formation without an increase in cell death and arrested rat aortic ring sprouting. In HUVEC, the IMD0354 treatment caused a dose-dependent reduction in VEGF-A expression, suppressed TNFα-stimulated expression of chemokines CCL2 and CXCL5, and diminished actin filament fibers and cell filopodia formation. In developing zebrafish embryos, IMD0354 treatment reduced expression of Vegf-a and disrupted retinal angiogenesis. In inflammation-induced angiogenesis in the rat cornea, systemic selective IKK2 inhibition decreased inflammatory cell invasion, suppressed CCL2, CXCL5, Cxcr2, and TNF-α expression and exhibited anti-angiogenic effects such as reduced limbal vessel dilation, reduced VEGF-A expression and reduced angiogenic sprouting, without noticeable toxic effect. In summary, targeting NF-κB by selective IKK2 inhibition dampened the inflammatory and angiogenic responses in vivo by modulating the endothelial cell expression profile and motility, thus indicating an important role of NF-κB signaling in the development of pathologic corneal neovascularization.

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Variation in guideline-concordant care for elderly patients with metastatic breast cancer in the United States

Abstract

Purpose

Prior studies have identified shortcomings in the quality of care for early-stage breast cancer. Guidelines recommend systemic therapy for metastatic breast cancer (MBC), but few studies have examined guideline concordance for these patients.

Methods

We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to identify patients aged ≥ 66 diagnosed in 2010–2011 with de novo MBC who were continuously enrolled in fee-for-service Medicare. We described initial care (within 6 months of diagnosis) for hormone receptor (HR)-positive/human epidermal receptor-2 (HER2)-negative, HER2-positive, and triple-negative (TN) tumors. We identified factors independently associated with receiving no initial systemic therapy, and compared hospice and hospital utilization for treated versus untreated patients.

Results

Among 446 patients, 65% were HR-positive, 21% were HER2-positive, and 14% were TN. Most patients (76.9%) received initial systemic treatment. Among treated HR-positive patients, 15% received chemotherapy as initial treatment; among treated HER2-positive patients, 34% did not receive HER2-targeted initial therapy. Factors independently associated with receiving no initial systemic therapy included older age (OR_{age continuous/year} = 1.08, 95% CI 1.04–1.11), being not married (OR_{not married vs. married} = 2.87, 95% CI 1.42–5.81), and subtype (OR_{TN vs. HR+} = 4.95, 95% CI 2.53–9.71). Of patients who did not receive initial systemic therapy, 41.1% did not receive hospice services.

Conclusions

In this population-based MBC cohort, almost one quarter did not receive initial systemic therapy and a substantial proportion of treated patients did not receive guideline-concordant first-line therapy. Further research should explore underuse of chemotherapy and HER2-targeted therapies, investigate whether patterns of care are consistent with patient preferences, and identify opportunities to optimize hospice utilization for patients not receiving treatment.

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Flow pattern analysis in Type B aortic dissection patients after stent-grafting repair: Comparison between complete and incomplete false lumen thrombosis

Abstract

Endovascular stent graft repair has become a common treatment for complicated Stanford Type B aortic dissection in order to restore true lumen flow and induce false lumen thrombosis. Using computational fluid dynamics, this study reports the differences in flow patterns and wall shear stress distribution in complicated Stanford Type B aortic dissection patients after endovascular stent graft repair. Five patients were included in this study: two having more than 80% false lumen thrombosis (Group 1), while three others had less than 80% false lumen thrombosis (Group 2) within one year following endovascular repair. Group 1 patients had concentrated re-entry tears around the abdominal branches only, while Group 2 patients had re-entry tears that spread along the dissection line. Blood flow inside the false lumen which affected thrombus formation, increased with the number of re-entry tears and when only small amounts of blood that entered the false lumen exited through the branches. In those cases where dissection extended below the abdominal branches (Group 2), patients with fewer re-entry tears and longer distance between the tears had low wall shear stress contributing to thrombosis. This work provides an insight into predicting the development of complete or incomplete false lumen thrombosis and, has implications for patient selection for treatment

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Oncological outcomes after cytoreductive nephrectomy for patients with metastatic renal cell carcinoma with inferior vena caval tumor thrombus

Abstract

Background

To evaluate the oncological outcomes of patients with metastatic renal cell carcinoma (mRCC) involving the inferior vena cava (IVC) who received cytoreductive nephrectomy.

Methods

This study included 75 consecutive metastatis renal cell carcinoma (mRCC) patients with inferior vena cava (IVC) tumor thrombus undergoing cytoreductive nephrectomy and tumor thrombectomy followed by systemic therapy.

Results

Of the 75 patients, 11, 33, 24 and 7 had level I, II, III and IV IVC thrombus, respectively. Following surgical treatment, 25 (group A), 27 (group B) and 23 (group C) received cytokine therapy alone, molecular-targeted therapy alone and both therapies, respectively, as management for metastatic diseases. The median overall survival (OS) of the 75 patients was 16.2 months. No significant differences in OS were noted according to the level of the IVC tumor thrombus. There were no significant differences in OS among groups A, B and C; however, OS in groups B and C was significantly superior to that in group A. Furthermore, multivariate analysis of several parameters identified the following independent predictors of poor OS—elevated C-reactive protein, liver metastasis and postoperative treatment with cytokine therapy alone.

Conclusions

The prognosis of mRCC patients with IVC thrombus undergoing cytoreductive nephrectomy may be significantly affected by the type of postoperative systemic therapy rather than the level of the IVC tumor thrombus. Accordingly, cytoreductive nephrectomy should be considered as a major therapeutic option for patients with mRCC involving the IVC, particularly in the era of targeted therapy.

http://ift.tt/2Fz9Fra

Eighty-five-year-old man with mosaic attenuation on chest imaging

Description

An 85-year-old man presented with worsening dyspnea and non-productive cough ongoing for 3 days prior to the admission. The patient denied any fever, chills, chest pain, palpitations, orthopnoea or paroxysmal nocturnal dyspnoea. Physical examination was remarkable for mild respiratory distress without any additional findings on auscultation. Social history was significant for >20 pack-year history of smoking. Vitals on admission: blood pressure 138/85, heart rate 92 bpm, respiratory rate 22, pO₂ 94% on room air. EKG was noticeable for normal sinus rhythm with ventricular rate of 87, without any ST-T wave changes.

A chest X-ray (CXR) was significant for hyperlucent lungs (figure 1). CT of chest without Intravenous contrast was performed to evaluate for possible atypical infection that could have been missed on the CXR.1 Areas of hypoattenuation are visible on the scan (figure 2A).

Figure 1

Chest X-ray showing hyperlucent lungs.

http://ift.tt/2mznZZ9

Torsion and rupture of a non-communicating rudimentary horn in a 17-week gestation in a 16-year-old girl: lessons learnt

A unicornuate uterus with non-communicating rudimentary horn has always been notorious and poses threat to continuation of pregnancy with dismal consequences. We are reporting an interesting case of uterine malformation with a 90° rotation of uterine axis which ultimately ruptured during termination of pregnancy. The rarity in our case was not only conception in non-communicating horn but also the complete twisting of axis which made the pregnant horn come in front of the non-gravid unicornuate uterus, mimicking normal pregnancy. The most important lesson learnt is that if induction does not lead to cervical changes and uterine contractions, one must consider atypical presentations of an anomalous uterus as a possible differential before proceeding further.

http://ift.tt/2qX22ri

Correction: A rare case of dual diagnosis in a 16-year-old girl with shortness of breath

de Vere F, House R, Gokdogan Y. A rare case of dual diagnosis in a 16-year-old girl with shortness of breath. BMJ Case Reports 2017. doi:10.1136/bcr-2017-221939.

There was an error in the published version of this article, in that the following statement was missed from the publication:

FDV and RH are joint first authors and contributed equally to this paper.

http://ift.tt/2mznApE

Relevance of enlarged cardiophrenic lymph nodes in determining prognosis of patients with advanced ovarian cancer

Ovarian cancer often presents at an advanced stage with widespread peritoneal and/or extra-abdominal metastases. Complete cytoreduction is the mainstay of treatment for disease confined to peritoneum. But in patients with distant metastases, the role and rationale is less obvious. One of the the most common sites of extra-abdominal disease is the cardiophrenic lymph node (CPLN). In this paper, we described the management of a patient with International Federation of Gynecology and Obstetrics (FIGO) stage IVB epithelial ovarian carcinoma and widespread peritoneal and extra-abdominal metastases to the CPLN, who underwent complete cytoreduction including excision of enlarged CPLN, following neoadjuvant chemotherapy. We examined the literature to determine the prognostic value of enlarged CPLN and their relevance in managing patients with advanced ovarian cancer and found it as an adverse prognostic factor. Transdiaphragmatic excision of CPLN is feasible without major complications. But as its correlation with overall or progression-free survival is not yet evident, large-scale prospective studies are warranted.

http://ift.tt/2r2KtGj

Combined sublethal irradiation and agonist anti-CD40 enhance donor T cell accumulation and control of autochthonous murine pancreatic tumors

Abstract

Tumor-reactive T lymphocytes can promote the regression of established tumors. However, their efficacy is often limited by immunosuppressive mechanisms that block T cell accumulation or function. ACT provides the opportunity to ameliorate immune suppression prior to transfer of tumor-reactive T cells to improve the therapeutic benefit. We evaluated the combination of lymphodepleting whole body irradiation (WBI) and agonist anti-CD40 (αCD40) antibody on control of established autochthonous murine neuroendocrine pancreatic tumors following the transfer of naïve tumor-specific CD8 T cells. Sublethal WBI had little impact on disease outcome but did promote T cell persistence in the lymphoid organs. Host conditioning with αCD40, an approach known to enhance APC function and T cell expansion, transiently increased donor T cell accumulation in the lymphoid organs and pancreas, but failed to control tumor progression. In contrast, combined WBI and αCD40 prolonged T cell proliferation and dramatically enhanced accumulation of donor T cells in both the lymphoid organs and pancreas. This dual conditioning approach also promoted high levels of inflammation in the pancreas and tumor, induced histological regression of established tumors, and extended the lifespan of treated mice. Prolonged survival was entirely dependent upon adoptive transfer, but only partially dependent upon IFNγ production by donor T cells. Our results identify the novel combination of two clinically relevant host conditioning approaches that synergize to overcome immune suppression and drive strong tumor-specific T cell accumulation within well-established tumors.

http://ift.tt/2D9xuHQ

Recent advances in metabolic engineering of Yarrowia lipolytica for lipid overproduction

Abstract

The non-conventional yeast Yarrowia lipolytica has been receiving growing attention due to its excellent lipid accumulation capacity. Microbial lipid has attracted widespread interest due to their broad applications as dietary supplements, cosmetic additives, oleochemicals and renewable starting materials for the production of fossil fuel. With the development of whole-genome sequencing, many effective genetic tools, including transformation systems, promoter systems, genomic integration and genome editing tools, have been applied in Y. lipolytica to enhance the overproduction of lipid. It can be genetically engineered for high lipid production via the upregulation of synthetic precursor and lipid synthesis pathways, the downregulation or disruption of competing pathways such as β-oxidation, and elimination of inhibitory factors. In this review, we summarize the lipid metabolism, available genetic tools, and recent advances in metabolic engineering of Y. lipolytica for the overproduction of lipid and lipid-derived chemicals. Future prospects of lipid biosynthesis in Y. lipolytica are discussed in light of the current progress, challenges, and trends in this field. Guidelines for future studies are also proposed.

Practical applications: General concerns about climate change, oil price crisis, and the increasing study for renewable energy are driving bio-lipid as promising alternatives to fossil fuel. Over the past few decades, microbial lipid has been widely applied in dietary supplements, cosmetic additives, oleochemicals and renewable starting materials for the production of fossil fuel. The non-conventional yeast Yarrowia lipolytica has become an attractive metabolic engineering host for the production of microbial lipids due to its ability to synthesize them in large quantities. This review illuminated the lipid biosynthesis and degradation of Y. lipolytica, and summarized the metabolic engineering efforts which have targeted a variety of biosynthetic biosynthetic pathway to efficiently convert carbon source to lipid in oleaginous Y. lipolytica.

http://ift.tt/2DrHPN8

Is there a social gradient of sarcopenia? A meta-analysis and systematic review protocol

Introduction

Sarcopenia (or loss of muscle mass and function) is a relatively new area within the field of musculoskeletal research and medicine. Investigating whether there is a social gradient, including occupation type and income level, of sarcopenia, as observed for other diseases, will contribute significantly to the limited evidence base for this disease. This new information may inform the prevention and management of sarcopenia and widen the evidence base to support existing and future health campaigns.

Methods and analysis

We will conduct a systematic search of the databases PubMed, Ovid, CINAHL, Scopus and EMBASE to identify articles that investigate associations between social determinants of health and sarcopenia in adults aged 50 years and older. Eligibility of the selected studies will be determined by two independent reviewers. The methodological quality of eligible studies will be assessed according to predetermined criteria. Established statistical methods to identify and control for heterogeneity will be used, and where appropriate, we will conduct a meta-analysis. In the event that heterogeneity prevents numerical synthesis, a best evidence analysis will be employed. This systematic review protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols reporting guidelines and will be registered with the International Prospective Register of Systematic Reviews (PROSPERO).

Ethics and dissemination

This systematic review will use published data, thus ethical permissions will not be required. In addition to peer-reviewed publication, our results will be presented at (inter)national conferences relevant to the field of sarcopenia, ageing and/or musculoskeletal health and disseminated both electronically and in print.

PROSPERO registration number

CRD42017072253.

http://ift.tt/2Dd4XkC

Right Iliac Fossa Pain Treatment (RIFT) Study: protocol for an international, multicentre, prospective observational study

Introduction

Patients presenting with right iliac fossa (RIF) pain are a common challenge for acute general surgical services. Given the range of potential pathologies, RIF pain creates diagnostic uncertainty and there is subsequent variation in investigation and management. Appendicitis is a diagnosis which must be considered in all patients with RIF pain; however, over a fifth of patients undergoing appendicectomy, in the UK, have been proven to have a histologically normal appendix (negative appendicectomy). The primary aim of this study is to determine the contemporary negative appendicectomy rate. The study's secondary aims are to determine the rate of laparoscopy for appendicitis and to validate the Appendicitis Inflammatory Response (AIR) and Alvarado prediction scores.

Methods and analysis

This multicentre, international prospective observational study will include all patients referred to surgical specialists with either RIF pain or suspected appendicitis. Consecutive patients presenting within 2-week long data collection periods will be included. Centres will be invited to participate in up to four data collection periods between February and August 2017. Data will be captured using a secure online data management system. A centre survey will profile local policy and service delivery for management of RIF pain.

Ethics and dissemination

Research ethics are not required for this study in the UK, as determined using the National Research Ethics Service decision tool. This study will be registered as a clinical audit in participating UK centres. National leads in countries outside the UK will oversee appropriate registration and study approval, which may include completing full ethical review. The study will be disseminated by trainee-led research collaboratives and through social media. Peer-reviewed publications will be published under corporate authorship including 'RIFT Study Group' and 'West Midlands Research Collaborative'.

http://ift.tt/2mtwDHt

Cohort profile: the Comparative Outcomes And Service Utilization Trends (COAST) Study among people living with and without HIV in British Columbia, Canada

Purpose

The Comparative Outcomes And Service Utilization Trends (COAST) Study in British Columbia (BC), Canada, was designed to evaluate the determinants of health outcomes and health care services use among people living with HIV (PLHIV) as they age in the period following the introduction of combination antiretroviral therapy (cART). The study also assesses how age-associated comorbidities and health care use among PLHIV may differ from those observed in the general population.

Participants

COAST was established through a data linkage between two provincial data sources: The BC Centre for Excellence in HIV/AIDS Drug Treatment Program, which centrally manages cART dispensation across BC and contains prospectively collected data on demographic, immunological, virological, cART use and other clinical information for all known PLHIV in BC; and Population Data BC, a provincial data repository that holds individual event-level, longitudinal data for all 4.6 million BC residents. COAST participants include 13 907 HIV-positive adults (≥19 years of age) and a 10% random sample inclusive of 516 340 adults from the general population followed from 1996 to 2013.

Findings to date

For all participants, linked individual-level data include information on demographics, health service use (eg, inpatient care, outpatient care and prescription medication dispensations), mortality, and HIV diagnostic and clinical data. Publications from COAST have demonstrated the significant mortality reductions and dramatic changes in the causes of death among PLHIV from 1996 to 2012, differences in the amount of time spent in a healthy state by HIV status, and high levels of injury and mood disorder diagnosis among PLHIV compared with the general population.

Future plans

To capture the dynamic nature of population health parameters, regular data updates and a refresh of the data linkage are planned to occur every 2 years, providing the basis for planned analysis to examine age-associated comorbidities and patterns of health service use over time.

http://ift.tt/2D9N6v8

Effectiveness and safety of oral sedation in adult patients undergoing dental procedures: protocol for a systematic review

Introduction

The management of anxious patients undergoing dental procedures is still a challenge in clinical practice. Despite a wide variety of drugs for oral sedation in adult patients, there are relatively few systematic reviews that compare the effectiveness and safety of different drugs administered via this route. Thus, this study will evaluate the effectiveness and safety of oral sedation with benzodiazepines and other agents to patients undergoing dental surgical procedures.

Method/design

We will conduct a systematic review and, if appropriate, a meta-analysis of randomised controlled clinical trials that will evaluate the use of conscious sedation administered orally to adult patients undergoing oral surgery. The search will be conducted using electronic databases, such as the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via Ovid), EMBASE (via Ovid), CINAHL (via Ovid), Lilacs (SciELO) and Capes database, without restriction of languages or date of publication. Primary outcomes include anxiety, sedation, treatment satisfaction, pain and adverse effects. Secondary outcomes include vital parameters (heart rate, respiratory rate and blood pressure) and patient cooperation during intervention. A team of reviewers will independently assess each citation for eligibility and in duplicates. For eligible studies, the same reviewers will perform data extraction, risk of bias assessment and determination of the overall quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation classification system.

Ethics and dissemination

The evidence gathered from this study should provide dental surgeons with knowledge on the effectiveness and safety of oral sedation in adults requiring dental surgical procedures. This in turn should contribute towards the decision-making process in dental practice, minimising the risks of anxiety and ineffective pain control in clinical procedures, as well as possible side effects. Ethics approval is not required in protocols for systematic reviews. The systematic review will be published in a peer-reviewed journal and presented at conferences.

PROSPERO registration number

CRD42017057142.

http://ift.tt/2mrBrNS

Temporal trends in antithrombotic treatment of real-world UK patients with newly diagnosed atrial fibrillation: findings from the GARFIELD-AF registry

Objective

To investigate evolving patterns in antithrombotic treatment in UK patients with newly diagnosed non-valvular atrial fibrillation (AF).

Design

Prospective, multicentre, international registry.

Setting

186 primary care practices in the UK.

Participants

3482 participants prospectively enrolled in four sequential cohorts (cohort 2 (C2) n=830, diagnosed September 2011 to April 2013; cohort 3 (C3) n=902, diagnosed April 2013 to June 2014; cohort 4 (C4) n=850, diagnosed July 2014 to June 2015; cohort 5 (C5) n=900, diagnosed June 2015 to July 2016). Participants had newly diagnosed non-valvular AF and at least one risk factor for stroke, were aged ≥18, and provided informed consent.

Main outcome measures

Antithrombotic treatment initiated at diagnosis, overall and according to stroke and bleeding risks. Stroke risk was retrospectively calculated using CHA₂DS₂-VASc (cardiac failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled)–vascular disease, age 65–74 and sex category (female)) and bleeding risk using HAS-BLED (hypertension, abnormal renal/liver function (1 point each), stroke, bleeding history or predisposition, elderly (>65), drugs/alcohol concomitantly (1 point each)).

Results

42.7% were women and the mean age was 74.5 years. The median CHA₂DS₂-VASc score was 3 in all cohorts and the median HAS-BLED score was 2 in all cohorts. There was a statistically significant increase in the use of anticoagulant therapy from C2 to C5 (C2 54.7%, C3 60.3%, C4 73.1%, C5 73.9%; P value for trend <0.0001). The increase in the use of anticoagulant was mainly in patients with CHA₂DS₂-VASc ≥2. The use of vitamin K antagonists (VKAs)±antiplatelet (AP) drugs decreased from C2 to C5 (C2 53.3%, C3 52.1%, C4 50.3%, C5 30.6%), while the use of non-vitamin K antagonist oral anticoagulants (NOACs)±AP increased (C2 1.3%, C3 8.0%, C4 22.7%, C5 43.3%). The use of AP only decreased (C2 36.4%, C3 25.5%, C4 11.9%, C5 10.5%), as did the combination therapy of VKA+AP (C2 13.6%, C3 11.0%, C4 9.6%, C5 5.8%).

Conclusion

There has been a progressive increase in the proportion of patients newly diagnosed with AF receiving guideline-recommended therapy in the UK, potentially driven by the availability of NOACs.

Trial registration number

NCT01090362; Pre-results.

http://ift.tt/2Dd4IGe

Understanding frailty: a qualitative study of European healthcare policy-makers approaches to frailty screening and management

Objective

To elicit European healthcare policy-makers' views, understanding and attitudes about the implementation of frailty screening and management strategies and responses to stakeholders' views.

Design

Thematic analysis of semistructured qualitative interviews.

Setting

European healthcare policy departments.

Participants

Seven European healthcare policy-makers representing the European Union (n=2), UK (n=2), Italy (n=1), Spain (n=1) and Poland (n=1). Participants were sourced through professional networks and the European Commission Authentication Service website and were required to be in an active healthcare policy or decision-making role.

Results

Seven themes were identified. Our findings reveal a 'knowledge gap', around frailty and awareness of the malleability of frailty, which has resulted in restricted ownership of frailty by specialists. Policy-makers emphasised the need to recognise frailty as a clinical syndrome but stressed that it should be managed via an integrated and interdisciplinary response to chronicity and ageing. That is, through social co-production. This would require a culture shift in care with redeployment of existing resources to deliver frailty management and intervention services. Policy-makers proposed barriers to a culture shift, indicating a need to be innovative with solutions to empower older adults to optimise their health and well-being, while still fully engaging in the social environment. The cultural acceptance of an integrated care system theme described the complexities of institutional change management, as well as cultural issues relating to working democratically, while in signposting adult care, the need for a personal navigator to help older adults to access appropriate services was proposed. Policy-makers also believed that screening for frailty could be an effective tool for frailty management.

Conclusions

There is potential for frailty to be managed in a more integrated and person-centred manner, overcoming the challenges associated with niche ownership within the healthcare system. There is also a need to raise its profile and develop a common understanding of its malleability among stakeholders, as well as consistency in how and when it is measured.

http://ift.tt/2Dd4Fu2

A study protocol for a non-randomised comparison trial evaluating the feasibility and effectiveness of a mobile cognitive-behavioural programme with integrated coaching for anxious adults in primary care

Introduction

Generalised anxiety disorder (GAD) and subclinical GAD are highly prevalent in primary care. Unmanaged anxiety worsens quality of life in patients seen in primary care practices and leads to increased medical utilisation and costs. Programmes that teach patients cognitive–behavioural therapy (CBT) techniques have been shown to improve anxiety and to prevent the evolution of anxiety symptoms to disorders, but access and engagement have hampered integration of CBT into medical settings.

Methods and analysis

This pragmatic study takes place in University of Pittsburgh Medical Center primary care practices to evaluate a coach-supported mobile cognitive– behavioural programme (Lantern) on anxiety symptoms and quality of life. Clinics were non-randomly assigned to either enhanced treatment as usual or Lantern. All clinics provide electronic screening for anxiety and, within clinics assigned to Lantern, patients meeting a threshold level of mild anxiety (ie, >5 on Generalised Anxiety Disorder 7-Item Questionnaire (GAD-7)) are referred to Lantern. The first study phase is aimed at establishing feasibility, acceptability and effectiveness. The second phase focuses on long-term impact on psychosocial outcomes, healthcare utilisation and clinic/provider adoption/sustainable implementation using a propensity score matched parallel group study design. Primary outcomes are changes in anxiety symptoms (GAD-7) and quality of life (Short-Form Health Survey) between baseline and 6-month follow-ups, comparing control and intervention. Secondary outcomes include provider and patient satisfaction, patient engagement, durability of changes in anxiety symptoms and quality of life over 12 months and the impact of Lantern on healthcare utilisation over 12 months. Patients from control sites will be matched to the patients who use the mobile app.

Ethics and dissemination

Ethics and human subject research approval were obtained. A data safety monitoring board is overseeing trial data and ethics. Results will be communicated to participating primary care practices, published and presented at clinical and scientific conferences.

Trial registration number

NCT03035019.

http://ift.tt/2mrjnTS

Family-focused practices in addictions: a scoping review protocol

Introduction

Families are significantly impacted by addictions and family involvement in treatment can reduce the harms and can also improve treatment entry, treatment completion and treatment outcomes for the individual coping with an addiction. Although the benefits of family-focused practices in addictions have been documented, services continue to have an individual focus and research on this topic is also limited. The objective of this study is to map the extent, range and nature of evidence available examining family interventions in addictions and identify gaps to guide future research, policy and practice.

Methods and analysis

This is a scoping review using the five-stage framework developed by Arksey and O'Malley. We will include published and unpublished empirical studies focusing on any type of family interventions in addiction treatment between 2000 and the present in English or French. A reviewer will search for literature that meets the inclusion criteria through the following electronic databases: MEDLINE, PsycINFO and Social Services Abstracts. For a comprehensive search, we will also hand-search reference lists, web sites and key journals. Data will be charted and sorted using a thematic analysis approach.

Ethics and dissemination

This review will be the first to examine all forms of family-focused practices for both substance use and problem gambling treatment for adults. It will provide information about existing service provisions and gaps in practice. This review can be used to start moving towards the development of best practices for families in addiction treatment. The results will be disseminated through a peer-reviewed journal and at mental health and addiction conferences.

http://ift.tt/2mtwC6n

Concealment of type 1 diabetes at work in Finland: a mixed-method study

Objectives

To explore the possible reasons for concealing type 1 diabetes (T1D) at work.

Methods

The main set of data came from a cross-sectional survey (response rate 49.3%), the participants of which were 688 wage earners with T1D. Concealment of T1D was measured by asking respondents have they ever during their working career hidden their diabetes from their (A) colleagues and (B) line manager. Furthermore, semistructured interviews (n=20) were conducted to obtain deeper understanding. Questionnaire data were analysed using logistic regression analyses and qualitative interviews with inductive thematic analysis.

Results

About 30% of wage earners with T1D had concealed their condition during their working career from their colleagues and almost 20% from their line manager. Individuals aged 18–44 years age were more likely to conceal their T1D from their colleagues than older workers during their working career. Not disclosing T1D to the extended family (OR 5.24 (95% CI 2.06 to 13.35)), feeling an outsider at work (OR 2.47 (95% CI 1.58 to 3.84)), being embarrassed by receiving special attention at work (OR 1.99 (95% CI 1.33 to 2.96)) and neglecting treatment at work (OR 1.59 (95% CI 1.01 to 2.48)) were all associated with concealment of T1D from colleagues. The youngest age group of 18–24 years were more likely to conceal their T1D from their line managers than the older age groups during their working career. Not disclosing T1D to the extended family (OR 4.41 (95% CI 1.72 to 11.32)), feeling like an outsider at work (OR 2.51 (1.52 to 4.14)) and being embarrassed by receiving special attention at work (OR 1.81 (95% CI 1.13 to 2.91)) were associated with concealment of T1D from line managers. From the interviews, five main themes related to concealment emerged, expressing fears related to the consequences of telling: (1) being perceived as weak, (2) job discrimination, (3) unwanted attention, (4) being seen as a person who uses their T1D for seeking advantages and (5) losing privacy.

Conclusions

A considerable proportion of wage earners with T1D are concealing their diagnosis often because of feelings associated with stigma. Both overemphasis and underestimation of T1D at work by the colleagues or line manager may lead to concealing T1D and may thus be harmful to self-management of T1D. The obstacles in disclosing T1D might be diminished by giving adequate information at the workplace about the condition and its significance.

http://ift.tt/2DbkgdG

What are the physical and psychological health effects of suicide bereavement on family members? An observational and interview mixed-methods study in Ireland

Objectives

Research focussing on the impact of suicide bereavement on family members' physical and psychological health is scarce. The aim of this study was to examine how family members have been physically and psychologically affected following suicide bereavement. A secondary objective of the study was to describe the needs of family members bereaved by suicide.

Design

A mixed-methods study was conducted, using qualitative semistructured interviews and additional quantitative self-report measures of depression, anxiety and stress (DASS-21).

Setting

Consecutive suicide cases and next-of-kin were identified by examining coroner's records in Cork City and County, Ireland from October 2014 to May 2016.

Participants

Eighteen family members bereaved by suicide took part in a qualitative interview. They were recruited from the Suicide Support and Information System: A Case-Control Study (SSIS-ACE), where family members bereaved by suicide (n=33) completed structured measures of their well-being.

Results

Qualitative findings indicated three superordinate themes in relation to experiences following suicide bereavement: (1) co-occurrence of grief and health reactions; (2) disparity in supports after suicide and (3) reconstructing life after deceased's suicide. Initial feelings of guilt, blame, shame and anger often manifested in enduring physical, psychological and psychosomatic difficulties. Support needs were diverse and were often related to the availability or absence of informal support by family or friends. Quantitative results indicated that the proportion of respondents above the DASS-21 cut-offs respectively were 24% for depression, 18% for anxiety and 27% for stress.

Conclusions

Healthcare professionals' awareness of the adverse physical and psychosomatic health difficulties experienced by family members bereaved by suicide is essential. Proactively facilitating support for this group could help to reduce the negative health sequelae. The effects of suicide bereavement are wide-ranging, including high levels of stress, depression, anxiety and physical health difficulties.

http://ift.tt/2mu6dp4

Is postoperative bracing after pedicle screw fixation of spine fractures necessary? Study protocol of the ORNOT study: a randomised controlled multicentre trial

Introduction

The most common surgical treatment of traumatic spine fractures is through a posterior approach using pedicle screws and rods. Postoperative treatment protocols including the use of postoperative orthoses however differ between hospitals and surgeons. A three-point hyperextension orthosis is designed to support proper posture and unload the anterior column. Some motion remains when wearing an orthosis, and its main value in postoperative treatment is therefore believed to be pain relief and patient confidence. This could consequently shorten recovery time. On the other hand, an orthosis could also lead to muscle weakness and slow down recovery. Any orthosis-related complications might also be avoided. Additionally, recent studies on conservative fracture treatment show no difference in radiological outcomes with or without an orthosis. To date, no randomised studies have been performed on the use of postoperative orthoses.

Methods and analysis

Patients undergoing posterior fixation with pedicle screws for a traumatic thoracolumbar fracture (T7–L4) will be included in this randomised controlled multicentre non-inferiority trial. Forty-six patients will be randomised 1:1 to one of the two parallel groups; one group will wear a postoperative orthosis for 6 weeks followed by 6 weeks of weaning and one group will not wear an orthosis. The primary outcome is pain at 6 weeks reported on the Numerical Rating Scale. Secondary outcomes consist of pain on other moments, analgesic use, complications and length of hospital stay, quality of life (EuroQuol 5 Dimensions), back pain-related function (Oswestry Disability Index) and radiological outcomes with a follow-up of 1 year. Orthosis compliance is monitored weekly in the orthosis group.

Ethics and dissemination

The institutional review board (METc VUmc) approved this study on 11 October 2016 under case number 2016.389. After completion of the trial, the results will be offered to an international scientific journal for peer-reviewed publication.

Trial registration number

NCT03097081 and NTR6285; Pre-results.

http://ift.tt/2DbSnSN

Clinical outcomes and prognostic factors in patients with spinal dural arteriovenous fistulas : a prospective cohort study in two Chinese centres

Background

The short-term outcomes and prognostic factors of patients with spinal dural arteriovenous fistulas (SDAVFs) have not been defined in large cohorts.

Objective

To define the short-term clinical outcomes and prognostic factors in patients with SDAVFs.

Methods

A prospective cohort of 112 patients with SDAVFs were included consecutively in this study. The patients were serially evaluated with the modified Aminoff and Logue's Scale (mALS) one day before surgery and at 3 months, 6 months and 12 months after treatment. Univariate and multivariate analyses were performed to identify demographic, clinical and procedural factors related to favourable outcome.

Results

A total of 94 patients (mean age 53.5 years, 78 were men) met the criteria and are included in the final analyses. Duration of symptom ranged from 0.5 to 66 months (average time period of 12.7 months). The location of SDAVFs was as follows: 31.6% above T7 level, 48.4% between T7 and T12 level (including T7 and T12) and 20.0% below T12 level. A total of 81 patients (86.2%) underwent neurosurgical treatment, 10 patients (10.6%) underwent endovascular treatment, and 3 patients (3.2%) underwent neurosurgical treatment after unsuccessful embolisation. A total of 78 patients demonstrated an improvement in mALS score of one point or greater at 12 months. Preoperative mALS score was associated with clinical improvement after adjusting for age, gender, duration of symptoms, location of fistula and treatment modality using unconditional logistic regression analysis (p<0.05).

Conclusion

Approximately four fifths of the patients experienced clinical improvement at 12 months and preoperative mALS was the strongest predictor of clinical improvement in the cohort.

http://ift.tt/2DdPiBJ

Postdischarge service utilisation and outcomes among Chinese and South Asian psychiatric inpatients in Ontario, Canada: a population-based cohort study

Objective

We sought to examine the short-term and long-term impacts of psychiatric hospitalisations among patients of Chinese and South Asian origin.

Design

Retrospective population-based cohort study using linked health administrative data.

Setting

We examined all adult psychiatric inpatients discharged between 1 April 2006 and 31 March 2014 in Ontario, Canada, who were classified as Chinese, South Asian and all other ethnicities (ie, 'general population') using a validated algorithm. We identified 2552 Chinese, 2439 South Asian and 127 142 general population patients.

Primary and secondary outcome measures

We examined psychiatric severity measures at admission and discharge and performed multivariable logistic regression analyses to examine 30-day, 180-day and 365-day postdischarge service utilisation and outcomes, comparing each of the ethnic groups with the reference population, after adjustment for age, sex, income, education, marital status, immigration status, community size and discharge diagnosis.

Results

Despite presenting to hospital with greater illness severity, Asian psychiatric inpatients had shorter lengths of hospital stay and greater absolute improvements in mental health and functional status at discharge compared with other inpatients. After hospitalisation, Chinese patients were more likely to visit psychiatrists and South Asian patients were more likely to seek mental healthcare from general practitioners. They were also less likely to have a psychiatric readmission or die 1 year following hospitalisation (adjusted OR_Chinese=0.87; 95% CI 0.79 to 0.97; adjusted OR_{South Asian}=0.82, 95% CI 0.73 to 0.91). Findings were consistent across genders, psychiatric diagnoses and immigrant groups.

Conclusion

Once hospitalised, patients of Chinese and South Asian origin fared as well as or better than general population patients at discharge and following discharge, and had a positive trajectory of psychiatric service utilisation.

http://ift.tt/2mqChdC

Now you see me: a pragmatic cohort study comparing first and final radiological diagnoses in the emergency department

Objectives

To (1) compare timely but preliminary and definitive but delayed radiological reports in a large urban level 1 trauma centre, (2) assess the clinical significance of their differences and (3) identify clinical predictors of such differences.

Design, setting and participants

We performed a retrospective record review for all 2914 patients who presented to our university affiliated emergency department (ED) during a 6-week period. In those that underwent radiological imaging, we compared the patients' discharge letter from the ED to the definitive radiological report. All identified discrepancies were assessed regarding their clinical significance by trained raters, independent and in duplicate. A binary logistic regression was performed to calculate the likelihood of discrepancies based on readily available clinical data.

Results

1522 patients had radiographic examinations performed. Rater agreement on the clinical significance of identified discrepancies was substantial (kappa=0.86). We found an overall discrepancy rate of 20.35% of which about one-third (7.48% overall) are clinically relevant. A logistic regression identified patients' age, the imaging modality and the anatomic region under investigation to be predictive of future discrepancies.

Conclusions

Discrepancies between radiological diagnoses in the ED are frequent and readily available clinical factors predict their likelihood. Emergency physicians should reconsider their discharge diagnosis especially in older patients undergoing CT scans of more than one anatomic region.

http://ift.tt/2DaYXsF

What are the characteristics of vitamin D metabolism in opioid dependence? An exploratory longitudinal study in Australian primary care

Objective

Compare vitamin D levels in opioid dependence and control population and adjust for relevant confounding effects. Nuclear hormone receptors (including the vitamin D receptor) have been shown to be key transducers and regulators of intracellular metabolism and comprise an important site of pathophysiological immune and metabolic dysregulation potentially contributing towards pro-ageing changes observed in opioid-dependent patients (ODPs).

Design

Longitudinal prospective comparing ODPs with general medical controls (GMCs).

Setting

Primary care.

Participants

Prospective review comparing 1168 ODP (72.5% men) and 415 GMC (51.6% men, p<0.0001). Mean ages were 33.92±0.31 (mean±SEM) and 41.22±1.32 years, respectively (p<0.0001). Opioid use in the ODP has been previously reported and shown to be typical.

Interventions

Nil. Observational study only.

Primary and secondary outcomes

Serum vitamin D levels and relevant biochemical parameters.

Results

Vitamin D levels were higher in the ODP (70.35±1.16 and 57.06±1.81 nmol/L, p<0.0001). The difference in ages between the two groups was handled in an age-matched case–control subanalysis and also by multiple regression. Sexes were analysed separately. The age:status (or age:time:status) was significant in case–control, cross-sectional and longitudinal analyses in both sexes (p<0.05). Modelled vitamin D was 62.71 vs 57.81 nmol/L in the two groups. Time-dependent mixed-effects models quadratic in age outperformed linear-only models (p=0.0377). ODP vitamin D was shown to vary with age and to correlate with alanine aminotransferase establishing it as a biomarker of age in this group. Hepatitis C seronegativity was significant in regression models (from p=0.0015).

Conclusion

Vitamin D was higher in ODP in both sexes in bivariate, cross-sectional, case–control and longitudinal analyses and was robust to the inclusion of metabolic and immune biomarkers. That Hepatitis C seronegativity was significant suggests opioid dependence has an effect beyond simply that of its associated hepatitides. This finding may relate to the accelerated ageing process previously described in opioid dependence.

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Long term exposure to cell phone frequencies (900 and 1800 MHz) induces apoptosis, mitochondrial oxidative stress and TRPV1 channel activation in the hippocampus and dorsal root ganglion of rats

Abstract

Mobile phone providers use electromagnetic radiation (EMR) with frequencies ranging from 900 to 1800 MHz. The increasing use of mobile phones has been accompanied by several potentially pathological consequences, such as neurological diseases related to hippocampal (HIPPON) and dorsal root ganglion neuron (DRGN). The TRPV1 channel is activated different stimuli, including CapN, high temperature and oxidative stress. We investigated the contribution TRPV1 to mitochondrial oxidative stress and apoptosis in HIPPON and DRGN following long term exposure to 900 and 1800 MHz in a rat model. Twenty-four adult rats were equally divided into the following groups: (1) control, (2) 900 MHz, and (3) 1800 MHz exposure. Each experimental group was exposed to EMR for 60 min/ 5 days of the week during the one year. The 900 and 1800 MHz EMR exposure induced increases in TRPV1 currents, intracellular free calcium influx (Ca²⁺), reactive oxygen species (ROS) production, mitochondrial membrane depolarization (JC-1), apoptosis, and caspase 3 and 9 activities in the HIPPON and DRGN. These deleterious processes were further increased in the 1800 MHz experimental group compared to the 900 MHz exposure group. In conclusion, mitochondrial oxidative stress, programmed cell death and Ca²⁺ entry pathway through TRPV1 activation in the HIPPON and DRGN of rats were increased in the rat model following exposure to 900 and 1800 MHz cell frequencies. Our results suggest that exposure to 900 and 1800 MHz EMR may induce a dose-associated, TRPV1-mediated stress response.

http://ift.tt/2AVuFVL

Survivorship care plan outcomes for primary care physicians, cancer survivors, and systems: a scoping review

Abstract

Purpose

With the focus on survivorship care-coordination between oncology and primary care providers (PCPs), there is a need to assess the research regarding the use of survivorship care plans (SCPs) and determine emerging research areas. We sought to find out how primary care physicians have been involved in the use of SCPs and determine SCP's effectiveness in improving care for cancer survivors. In this scoping review, we aimed to identify gaps in the current research and reveal opportunities for further research.

Methods

We followed the methodology for scoping studies which consists of identifying the research question, locating relevant studies, selecting studies, charting the data, and collating, summarizing, and reporting the results.

Results

Out of 5375 original articles identified in the literature search, 25 met the inclusion/exclusion criteria. Eight articles examined PCP-only related outcomes, eight examined survivor-only related outcomes, eight examined mixed outcomes between both groups, and one examined system-based outcomes. Findings highlighted several areas where SCPs may provide benefits, including increased confidence among PCPs in managing the care of survivors and increased quality of life and well-being for survivors. This research also highlighted the need for careful consideration of SCP mode of delivery and content in order to maximize their utility to patients and providers.

Conclusions

Based on the findings of this review, SCPs may benefit providers and health care systems, but the benefits to patients remain unclear. Further research on the potential benefits of SCPs to particular patient populations is warranted.

Implications for Cancer Survivors

SCPs appear to be beneficial to PCPs in improving overall quality of care. However, more work needs to be done to understand the direct impact on cancer survivors.

http://ift.tt/2AWk9O7

Outbreak and management of Mycoplasma gallisepticum infection in desi chicken and turkey flocks in an organized mixed farm

Abstract

In an organized farm, desi chicken and turkeys were reported with the clinical signs of congestion of conjunctival mucous membrane, dullness, unilateral and bilateral head swelling and nasal discharge. Flock strength was 545 desi chickens and 296 turkeys of 75 and 50 days old respectively. Morbidity was 3.67 and 6.75% and mortality was 0.91 and 0.67% in chickens and turkeys respectively. On investigation, clinical signs started 12 days after the introduction of desi chicken from another organized farm. In total, 10 chickens and 20 turkeys showed clinical signs, of which 5 desi chicken and 2 turkeys died. On necropsy, the birds showed congestion of conjunctival mucous membrane, unilateral and bilateral infraorbital sinus swelling and caseous material with mucous exudates in the infraorbital sinus. Lungs were congested and edematous. Thoracic and abdominal air sacs were cloudy with beaded appearance, thickened with yellowish caseous material. Infraorbital sinus and ocular swab were collected from live birds. Infraorbital sinus swab, lung and air sacs were collected from dead birds. Mycoplasma gallisepticum was isolated from infraorbital sinus and air sac samples and was also confirmed by polymerase chain reaction. Histopathologically, mucopurulent sinusitis and airsacculitis were noticed. The Mycoplasma gallisepticum outbreak was effectively controlled by using effective treatment with 1% Tylosin and following strict bio-security measures.

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The Endoscopic Band Ligation for colonic diverticular bleeding

Abstract

Colonic diverticular bleeding presents with sudden painless hematochezia. Bleeding often occurs from the right hemi colon with only 6 to 42% of them can be identified.¹ Spontaneous hemostasis can be expected up to 70 to 80%, however, 20 to 40% encounter rebleeding.

This article is protected by copyright. All rights reserved.

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Consideration of population and cultural factors in American Indian/Alaskan Native (AIAN) research

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The association between smoking and cancer incidence in BRCA1 and BRCA2 mutation carriers

Abstract

Tobacco smoke is an established carcinogen, but the association between tobacco smoking and cancer risk in BRCA mutation carriers is not clear. The aim of this study was to evaluate prospectively the association between tobacco smoking and cancer incidence in a cohort of BRCA1 and BRCA2 mutation carriers. The study population consisted of unaffected BRCA mutation carriers. Information on lifestyle including smoking histories, reproductive factors, and past medical histories was obtained through questionnaires. Incident cancers were updated biennially via follow-up questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using time-dependent Cox regression models. There were 700 incident cancers diagnosed over 26,711 person-years of follow-up. The most frequent cancers seen in BRCA mutation carriers were breast (n = 428; 61%) and ovarian (n = 109; 15%) cancer. Compared to non-smokers, (ever) smoking was associated with a modest increased risk of all cancers combined (HR = 1.17; 95%CI 1.01-1.37). Women in the highest group of total pack-years (4.3-9.8) had an increased risk of developing any cancer (HR = 1.27; 95%CI 1.04-1.56), breast cancer (HR=1.33, 95%CI 1.02-1.75), and ovarian cancer (HR = 1.68; 95%CI 1.06-2.67) compared to never smokers. The associations between tobacco smoking and cancer did not differ by BRCA mutation type or by age at diagnosis. This prospective study suggests that tobacco smoking is associated with a modest increase in the risks of breast and ovarian cancer among women with BRCA1 or BRCA2 mutation. This article is protected by copyright. All rights reserved.

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Reproductive history, breast-feeding and risk of triple negative breast cancer: The Breast Cancer Etiology in Minorities (BEM) Study

Abstract

Few risk factors have been identified for triple negative breast cancer (TNBC) which lacks expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This more aggressive subtype disproportionately affects some racial/ethnic minorities and is associated with lower survival. We pooled data from three population-based studies (558 TNBC and 5,111 controls) and examined associations of TNBC risk with reproductive history and breast-feeding. We estimated odds ratios (OR) and 95% confidence intervals (CI) using multivariable logistic regression. For younger women, aged <50 years, TNBC risk was increased two-fold for parous women who never breast-fed compared to nulliparous women (OR=2.02, 95% CI=1.12-3.63). For younger parous women, longer duration of lifetime breast-feeding was associated with a borderline reduced risk (≥24 vs. 0 months: OR=0.52, 95% CI=0.26-1.04, P trend=0.06). Considering the joint effect of parity and breast-feeding, risk was increased two-fold for women with ≥3 full-term pregnancies (FTPs) and no or short-term (<12 months) breast-feeding compared to women with 1-2 FTPs and breast-feeding ≥12 months (OR=2.56, 95% CI=1.22-5.35). None of these associations were observed among older women (≥50 years). Differences in reproductive patterns possibly contribute to the racial/ethnic differences in TNBC incidence. Among controls aged <50 years, the prevalence of no or short-term breast-feeding and ≥3 FTPs was highest for Hispanics (22%), followed by African Americans (18%), Asian Americans (15%), and non-Hispanic whites (6%). Breast-feeding is a modifiable behavioral factor that may lower TNBC risk and mitigate the effect of full-term pregnancies in women under age 50 years. This article is protected by copyright. All rights reserved.

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Sequential versus simultaneous use of chemotherapy and gonadotropin-releasing hormone agonist (GnRHa) among estrogen receptor (ER)-positive premenopausal breast cancer patients: effects on ovarian function, disease-free survival, and overall survival

Abstract

Objective

To investigate ovarian function and therapeutic efficacy among estrogen receptor (ER)-positive, premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonist (GnRHa) and chemotherapy simultaneously or sequentially.

Method

This study was a phase 3, open-label, parallel, randomized controlled trial (NCT01712893). Two hundred sixteen premenopausal patients (under 45 years) diagnosed with invasive ER-positive breast cancer were enrolled from July 2009 to May 2013 and randomized at a 1:1 ratio to receive (neo)adjuvant chemotherapy combined with sequential or simultaneous GnRHa treatment. All patients were advised to receive GnRHa for at least 2 years. The primary outcome was the incidence of early menopause, defined as amenorrhea lasting longer than 12 months after the last chemotherapy or GnRHa dose, with postmenopausal or unknown follicle-stimulating hormone and estradiol levels. The menstrual resumption period and survivals were the secondary endpoints.

Result

The median follow-up time was 56.9 months (IQR 49.5–72.4 months). One hundred and eight patients were enrolled in each group. Among them, 92 and 78 patients had complete primary endpoint data in the sequential and simultaneous groups, respectively. The rates of early menopause were 22.8% (21/92) in the sequential group and 23.1% (18/78) in the simultaneous group [simultaneous vs. sequential: OR 1.01 (95% CI 0.50–2.08); p = 0.969; age-adjusted OR 1.13; (95% CI 0.54–2.37); p = 0.737]. The median menstruation resumption period was 12.0 (95% CI 9.3–14.7) months and 10.3 (95% CI 8.2–12.4) months for the sequential and simultaneous groups, respectively [HR 0.83 (95% CI 0.59–1.16); p = 0.274; age-adjusted HR 0.90 (95%CI 0.64–1.27); p = 0.567]. No significant differences were evident for disease-free survival (p = 0.290) or overall survival (p = 0.514) between the two groups.

Conclusion

For ER-positive premenopausal patients, the sequential use of GnRHa and chemotherapy showed ovarian preservation and survival outcomes that were no worse than simultaneous use. The application of GnRHa can probably be delayed until menstruation resumption after chemotherapy.

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Fumarate hydratase (FH) deficiency in uterine leiomyomas: recognition by histological features versus blind immunoscreening

Abstract

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is a rare autosomal dominant disease caused by germline mutations in the fumarate hydratase (FH) gene. Affected individuals develop cutaneous and uterine leiomyomas and aggressive RCC. To date, only few publications described the frequency and morphology of FH-deficient uterine leiomyomas. We reviewed 22 cases collected over 8 years from routine and consultation files based on distinctive histological features. In addition, we screened 580 consecutive uterine leiomyomas from 484 patients, 23 extra-uterine and 8 uterine leiomyosarcomas, and 6 leiomyomas with bizarre nuclei for FH loss using immunohistochemistry (IHC) on tissue microarrays (TMAs). All 22 FH-deficient cases were suspected on H&E sections and confirmed by FH IHC. Patients' ages ranged from 25 to 70 years (median 36). Seventeen patients had multiple nodules (2–14) measuring up to 11.8 cm. None of the patients had stigmata or family history of the HLRCC syndrome. Histologically, all FH-deficient tumors showed consistent and reproducible features as reported previously. FH loss was detected in 2/534 evaluable leiomyomas (0.4%), but in none of leiomyosarcomas. Two of six leiomyomas with bizarre nuclei were FH-deficient. FH-deficient uterine leiomyomas are rare in routine material (= 0.4%). They can be reliably identified or suspected by consistent morphological features. Our data showed predictive morphology to be superior to blind IHC screening for detecting them. The relationship of FH-deficient uterine smooth muscle tumors to the HLRCC syndrome needs further clarification.

http://ift.tt/2D6b9vA

Spectrum of bone marrow pathology and hematological abnormalities in methylmalonic acidemia

Patients with isolated methylmalonic acidemia (MMA) may present with a wide range of hematological complications including anemia, leukopenia, thrombocytopenia, and pancytopenia. However, there are very limited data on the development of hemophagocytosis or myelodysplasia in these patients. We report three patients with isolated MUT related MMA who presented with severe refractory pancytopenia during acute illness. Their bone marrow examination revealed a wide spectrum of pathology varying from bone marrow hypoplasia, hemophagocytosis to myelodysplasia with ring sideroblasts. We discuss their management and outcome. This report emphasizes the need for bone marrow examination in these patients with refractory or unexplained severe cytopenia, to confirm bone marrow pathology, and to rule out other diseases with similar clinical presentation for a better clinical outcome.

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Vernal keratoconjunctivitis

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Does herpes zoster predispose to giant cell arteritis: a geo-epidemiologic study

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Parents’ Judgments about the Desirability of Toys for Their Children: Associations with Gender Role Attitudes, Gender-typing of Toys, and Demographics

Abstract

Parental toy selection and responses to toy play are important factors in children's gender socialization. Reinforcing play with same-gender-typed toys guides children's activities and limits their action repertoires in accordance with gender stereotypes. A survey of 324 Austrian parents of three- to six-year-old children was conducted to investigate parents' judgments about the desirability of different types of toys for their children and how these judgements relate to parents' gender-typing of toys, gender role attitudes, and demographics (age, education, gender). Results show that parents rated same-gender-typed and gender-neutral toys as more desirable for their children than cross-gender-typed toys. The traditionalism of parents' gender role attitudes was not associated with their desirability judgments of same-gender-typed toys, but was negatively related to their desirability judgments of cross-gender-typed toys. This indicates that egalitarian parents permit a greater range of interests and behaviors in their children than traditional parents do. Younger parents, parents with lower educational levels, and fathers reported more traditional gender role attitudes than did older parents, parents with higher educational levels, and mothers. However, no differences based on age, educational level or gender were found in parents' judgments of toy desirability. The present study demonstrates that parents' judgments about the desirability of toys for their children do not accurately reflect their gender role attitudes. This finding highlights the importance of simultaneously investigating different aspects of parents' gender-related attitudes in order to gain a better understanding of parental transmission of gender stereotypes.

http://ift.tt/2CXsUZL