Pure intraductal carcinoma of the parotid gland: Cytologic findings on FNA sample. Report of one case

One case of intraductal carcinoma of the parotid gland in a 67-year-old male patient is here introduced. The patient, who had a one-year history of a parotid mass, had undergone ultrasound and MRI examination that disclosed a 13x4x3 mm well delimited nodular mass of the accessory lobe of his left parotid gland. Ultrasound-guided Fine Needle Aspiration (FNA) had been performed by the clinician. The obtained smears showed widespread cellular necrosis in which cellular clusters with moderate and focally severe atypias displayed papillary and cribriform architecture and were admixed with sheets of epithelial cells with less striking nuclear atypias, squamous, or apocrine metaplasia. Histopathological examination disclosed a pure intraductal carcinoma of the parotid gland with classical morphology, which was radically excised. The differential cytological diagnosis of pure intraductal carcinoma of salivary glands may be difficult and comprises mucoepidermoid carcinoma as well as "in situ" carcinomas developping in the context of sclerosing polycystic adenosis, mammary analogue secretory carcinoma (MASC) of the salivary glands and cystic variants of salivary adenocarcinoma NOS (formerly called cystadenocarcinomas).

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Dosage effects of ZP2 and ZP3 heterozygous mutations cause human infertility

Abstract

The zona pellucida (ZP) is an extracellular matrix universally surrounding mammalian eggs, which is essential for oogenesis, fertilization, and pre-implantation embryo development. Here, we identified two novel heritable mutations of ZP2 and ZP3, both occurring in an infertile female patient with ZP-abnormal eggs. Mouse models with the same mutations were generated by CRISPR/Cas9 gene editing system, and oocytes obtained from female mice with either single heterozygous mutation showed approximately half of the normal ZP thickness compared to wild-type oocytes. Importantly, oocytes with both heterozygous mutations showed a much thinner or even missing ZP that could not avoid polyspermy fertilization, following the patient's pedigree. Further analysis confirmed that precursor proteins produced from either mutated ZP2 or ZP3 could not anchor to oocyte membranes. From these, we conclude that ZP mutations have dosage effects which can cause female infertility in humans. Finally, this patient was treated by intracytoplasmic sperm injection (ICSI) with an improved culture system and successfully delivered a healthy baby.

http://ift.tt/2s1jqvp

A time for psycho-spiritual transcendence: The experiences of Iranian women of pain during childbirth

Publication date: Available online 23 June 2017
Source:Women and Birth
Author(s): Z. Taghizdeh, A. Ebadi, M. Dehghani, M. Gharacheh, P. Yadollahi
BackgroundThe description of women's experiences of childbirth improves our understandings of the nature of childbirth, women's suffering and pain during childbirth.AimThis study aimed to explore women's experiences of pain during childbirth.MethodA qualitative study was conducted using a conventional content analysis method proposed by Graneheim and Lundman (2004). In-depth face to face semi-structured interviews were held with 17 women who met inclusion criteria for participation in this study.FindingsThe women's experiences of pain during childbirth was described as 'a time for psycho-spiritual transcendence'. Categories developed during the data analysis were 'conflicting emotions towards pain', 'new insight towards labor pain', 'self-actualization' and 'spiritual development'.ConclusionMost participants had positive experiences and attitudes towards pain during childbirth influenced by cultural, context and religious factors. According to this study, 'transcendental progression' was an eminent feeling that created positive inner feelings along with self-actualization in women. This provides a new insight on labor pain and helps healthcare providers understand the effect of pain during childbirth on women's spiritual, mental and psychological needs.



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Argininosuccinate synthase 1 (ASS1): A marker of unclassified hepatocellular adenoma and high bleeding risk

Abstract

Hepatocellular adenomas (HCA) are rare benign tumors divided into three main subgroups defined by patho-molecular features, HNF1A (H-HCA), mutated β-catenin (b-HCA) and inflammatory (IHCA). In the case of unclassified HCA (UHCA), which are currently identified by default, a high risk of bleeding remains a clinical issue. The objective of this study was to explore UHCA proteome with the aim to identify specific biomarkers. Following dissection of the tumoral (T) and non-tumoral (NT) tissue on formalin-fixed paraffin-embedded (FFPE) from HCA tissue sections using laser capture methodology, we performed mass spectrometry analysis to compare T and NT protein expression levels in HCA, H-HCA, IHCA, b-HCA, UHCA and focal nodular hyperplasia. Using this methodology, we searched for proteins, which are specifically deregulated in UHCA. We demonstrate that proteomic profiles allow discriminating known HCA subtypes through the identification of classical biomarkers in each HCA subgroup. We observed specific upregulation of the arginine synthesis pathway associated with overexpression of argininosuccinate synthase (ASS1) and arginosuccinate lyase (ASL) in UHCA. ASS1 immunohistochemistry identified all the UHCA, of which 64.7% presented clinical bleeding manifestations. Interestingly, we demonstrated that the significance of ASS1 was not restricted to UHCA but also encompassed certain hemorrhagic cases in other HCA subtypes, particularly inflammatory HCA.

Conclusion: ASS1+ HCA combined with a typical hematoxylin and eosin stain aspect defined a new HCA subgroup at a high risk of bleeding. This article is protected by copyright. All rights reserved.

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Alcohol abstinence in patients surviving an episode of alcoholic hepatitis: Prediction and impact on long-term survival

ABSTRACT

Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease. Most studies have focused on short-term prognosis, while factors associated with long-term survival are largely unknown. The aims of our study were: 1) to determine the impact of complete abstinence from alcohol on long-term survival and 2) to identify prognostic factors at admission capable of predicting abstinence during long-term follow-up in patients with AH. One hundred and forty-two patients with biopsy-proven AH that survived the first episode were included. Demographic, psychiatric and biochemical variables at admission and drinking status during follow-up were obtained. Cox regression, logistic regression and classification and regression trees (CART) analyses were used for statistical analysis. Overall mortality was 38% with a median follow-up of 55 months. During follow-up, complete abstinence was reported in 39% and was associated with better long-term survival (HR 0.53; p=0.03). After adjustment for baseline prognostic scoring systems (MELD and ABIC scores), complete abstinence was independently associated with survival (p<0.05). Age and lack of prior alcoholism treatments were independently associated with complete abstinence (p<0.001 and p=0.02, respectively) during follow-up. CART analysis generated a simple and practical algorithm based-on the combination of prior alcoholism treatments and age. Using CART analysis we stratified 2 subgroups of patients with high (65%) and low (26-29%) rates of complete abstinence after an episode of AH.

Conclusions: Complete abstinence after an episode of AH positively impacts long-term survival. The combination of 2 variables easily obtained at admission might be useful to predict long-term abstinence after an episode of AH. Strategies aimed at promoting alcohol abstinence in these patients are mandatory. This article is protected by copyright. All rights reserved.

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Prospero-related homeobox 1 drives angiogenesis of hepatocellular carcinoma through selectively activating IL-8 expression

ABSTRACT

Angiogenesis has been proven to play an important role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanism underlying HCC angiogenesis is not well understood. In this study, Prospero-related homeobox 1 (PROX1) was identified as a novel pro-angiogenic factor in HCC cell lines and tissues. A strong positive correlation was found between the levels of PROX1 and microvessel density in HCC tissues. Knockdown of PROX1 expression in HCC cells significantly inhibited the in vitro capillary tube formation by human vascular endothelial cells and in vivo angiogenesis of HCC, while overexpression of PROX1 in HCC cells induced the opposite effects. PROX1 and NF-κB p65 expression levels were positively correlated in both HCC tissues and cell lines. PROX1 could enhance the nuclear accumulation of p65 and stabilizes p65 by recruiting ubiquitin specific protease 7 (USP7) to prevent p65 ubiquitination. Consequently, PROX1 activated the NF-κB signaling and selectively promoted the expression of the pro-angiogenic IL-8 by epigenetically stimulating the IL-8 promoter. Finally, progression of high PROX1 expression HCC in tumor xenograft mice could be effectively contained by an anti-IL-8 mAb. Conclusions: We have identified PROX1 as a crucial promoter of HCC angiogenesis. Our study provides a novel insight into PROX1's function in HCC progression and the potential therapeutic application of anti-IL-8 antibody in high PROX1 expression HCC patients. This article is protected by copyright. All rights reserved.

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Letter to the editor: Authors' Reply: Healthy Controls in Non-Alcoholic Fatty Liver Disease Management: A Biomedical Research Perspective

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Letter to the editor: Healthy Controls in Non-Alcoholic Fatty Liver Disease Management: a Biomedical Research Perspective

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Targeting Histone deacetylase 4/Ubc9 impairs DNA repair for radiosensitization of hepatocellular carcinoma cells

Abstract

Several strategies to improve the efficacy of radiation therapy against hepatocellular carcinoma (HCC) have been investigated. One approach was to develop radiosensitizing compounds. Because histone deacetylase 4 (HDAC4) is highly expressed in liver cancer and known to regulate oncogenesis through chromatin structure remodeling and controlling protein access to DNA, we postulated that HDAC4 inhibition might enhance radiation's effect on HCC cells. HCC cell lines (Huh7 and PLC5) and an ectopic xenograft were pretreated with HDAC inhibitor or shRNA to knock down expression of HDAC4, and then irradiated (2.5-10 Gy). We evaluated cell survival by a clonogenic assay; apoptosis by annexin-V immunofluorescence; γH2AX, Rad51, and HDAC4 by immunofluorescence staining; HDAC4, Rad51, and Ubc9 in HCC cell nuclei by cell fractionation and confocal microscopy; physical interaction between HDAC4/Rad51/Ubc9 by immunoprecipitation; the downstream targets of HDAC4 knockdown by immunoblotting. Both HDAC4 knockdown and HDAC inhibitor enhanced radiation-induced cell death, and reduced homologous recombination repair of DNA double-strand breaks and Akt activation, leading to increased apoptosis. HDAC4 knockdown with or without an HDAC inhibitor significantly delayed tumor growth in a radiation-treated xenograft model. Radiation stimulated nuclear translocation of Rad51 in an HDAC4-dependent manner and the binding of Ubc9 directly to HDAC4, which led to Ubc9 acetylation. Moreover, these effects were accompanied by HDAC4/Ubc9/Rad51 complex dissociation through inhibiting nuclear translocation. Conclusions: HDAC4 signaling blockade enhances radiation-induced lethality in HCC cells and xenografts. These findings raise the possibility that HDAC4/Ubc9/Rad51 complex in DNA repair may be a target for radiosensitization of HCC. This article is protected by copyright. All rights reserved.

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The Liver-Gut Microbiota Axis Modulates Hepatotoxicity of Tacrine in the Rat

Abstract

The gut microbiota possesses diverse metabolic activities but its contribution towards heterogeneous toxicological responses is poorly understood. Here, we elucidate the role of the liver-gut microbiota axis in underpinning the hepatotoxicity of tacrine. We employed an integrated strategy combining pharmacokinetics, toxicology, metabonomics, genomics and metagenomics to elucidate and validate the mechanism of tacrine-induced hepatotoxicity in Lister hooded rats. Pharmacokinetic studies in rats demonstrated 3.3-fold higher systemic exposure to tacrine in strong responders that experienced transaminitis, revealing enhanced enterohepatic recycling of deglucuronidated tacrine in this subgroup, not attributable to variation in hepatic disposition gene expression. Metabonomic studies implicated variation in gut microbial activities that mapped onto tacrine-induced transaminitis. Metagenomics delineated greater deglucuronidation capabilities in strong responders, based on differential gut microbial composition (e.g. Lactobacillus, Bacteroides and Enterobacteriaceae) and ∼9% higher β-glucuronidase gene abundance compared to non-responders. In the validation study, co-administration with oral β-glucuronidase derived from Escherichia coli and pre-treatment with vancomycin and imipenem significantly modulated the susceptibility to tacrine-induced transaminitis in vivo. Conclusion: Our study establishes the pertinent gut microbial influences in defining the hepatotoxicity of tacrine, providing crucial insights for personalized medicine initiatives. This article is protected by copyright. All rights reserved.

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Hepatic stimulator substance resists hepatic ischemia-reperfusion injury by regulating Drp1 translocation and activation

Abstract

Ischemia-reperfusion injury (IRI), induced by abnormal mitochondrial fission related apoptosis, is a major concern in liver transplantation settings. Our previous studies have demonstrated that hepatic stimulator substance (HSS) is an anti-apoptotic effector and could protect liver from IRI. However, the underlying mechanism remains unclear. In the present study, we report that in vitro and in vivo HSS could regulate mitochondrial fission and hepatocyte apoptosis during liver IRI by orchestrating the translocation and activation of dynamin-related protein 1 (Drp1). Using a mouse model of IR-induced liver injury, we found that HSS haploinsufficient (HSS^+/-) mice displayed exacerbated liver damage based on their increased serum aminotransferase levels, cell structural destruction, and apoptosis levels compared to the wild type (HSS^+/+) littermates. Disruption of HSS markedly increased cyclin-dependent kinase 1 (CDK1) and Bax expression, accompanied with elevated p-Drp1 and release of cytochrome c. In parallel in vitro studies, we found that HSS could inhibit the expression of CDK1 and that HSS inhibits hepatocytes apoptosis through its suppression of CDK1/cyclin B -mediated phosphorylation at Ser-616 of Drp1, thereby decreasing Drp1 accumulation in mitochondria and Drp1-mediated activation of the mitochondrial fission program. On the contrary, knockdown of HSS increased of CDK1 as well as Drp1 phosphorylation and aggravated hepatocellular apoptosis. Mechanistic investigation showed that HSS was able to reduce the stability and translation of CDK1 mRNA by modulating the expression of several miRNAs, including miR-410-3p, miR-490-3p and miR-582-5p. Our data reveal a novel mechanism for HSS in regulating the mitochondrial fission machinery and further suggest that modulation of HSS may provide a therapeutic approach for combating liver damage. This article is protected by copyright. All rights reserved.

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Hepatic bile acid uptake in humans and mice: Multiple pathways and expanding potential role for gut-liver signaling

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A first-time-in-human study of GSK2636771, a phosphoinositide 3 kinase beta-selective inhibitor, in patients with advanced solid tumors

Purpose: The phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT) pathway is commonly activated in several tumor types. Selective targeting of p110β could result in successful pathway inhibition while avoiding the on and off target effects of pan-PI3K inhibitors. GSK2636771 is a potent, orally bioavailable, adenosine triphosphate-competitive, selective inhibitor of PI3Kβ.<br /><br />Experimental Design: <p>We evaluated the safety, pharmacokinetics, pharmacodynamics and antitumor activity of GSK2636771 to define the recommended Phase II dose (RP2D). During the dose-selection and dose-escalation stages (Parts 1 and 2), patients with phosphatase and tensin homolog (PTEN)-deficient advanced solid tumors received escalating doses of GSK2636771 (25-500 mg once daily [QD]) using a modified 3+3 design to determine the RP2D; tumor type-specific expansion cohorts (Part 3) were implemented to further assess tumor responses at the RP2D.</p> <br />Results: A total of 65 patients were enrolled; dose-limiting toxicities were hypophosphatemia and hypocalcemia. Adverse events included diarrhea (48%), nausea (40%), and vomiting (31%). Single- and repeat-dose exposure increased generally dose proportionally. GSK2636771 400 mg QD was the RP2D. Phospho/total AKT ratio decreased with GSK2636771 in tumor and surrogate tissue. A castrate-resistant prostate cancer (CRPC) patient harboring PIK3CB amplification had a partial response for over a year; an additional 10 patients derived durable (≥24 weeks) clinical benefit, including 2 other patients with CRPC with PIK3CB alterations (≥34 weeks). GSK2636771 400 mg QD oral induced sufficient exposure and target inhibition with a manageable safety profile.<br /><br />Conclusions: Genomic aberrations of PIK3CB may be associated with clinical benefit from GSK2636771.

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Mutational Heterogeneity in APC and KRAS Arises at the Crypt level and Leads to Polyclonality in Early Colorectal Tumorigenesis

Purpose:  The majority of genomic alterations causing intratumoral heterogeneity (ITH) in colorectal cancer (CRC) are thought to arise during early stages of carcinogenesis as a burst but only after truncal mutations in APC have expanded a single founder clone. We have investigated if the initial source of ITH is consequent to multiple independent lineages derived from different crypts harboring distinct truncal APC and driver KRAS mutations, thus challenging the prevailing monoclonal monocryptal model. <p>Experimental design: High-depth next-generation sequencing and SNP arrays were performed in whole lesion extracts of 37 FAP colorectal adenomas. Also, ultra-sensitive genotyping of hotspot mutations of APC and KRAS was performed using nanofluidic PCRs in matched bulk biopsies (n=59) and crypts (n=591) from 18 adenomas and 7 carcinomas and adjacent normal tissues.</p> <p>Results: Multiple co-occurring truncal APC and driver KRAS alterations were uncovered in whole lesion extracts from adenomas and subsequently confirmed to belong to multiple clones. Ultra-sensitive genotyping of bulk biopsies and crypts revealed novel undetected APC mutations that were prominent among carcinomas, whereas abundant wild-type APC crypts were detected in adenomas. KRAS mutational heterogeneity within crypts was evident in both adenomas and carcinomas with a higher degree of concordance between biopsy and crypt genotyping in carcinomas. Non-random heterogeneity among crypts was also observed.</p> Conclusions: The striking degree of non-random intercrypt heterogeneity in truncal and driver gene mutations observed in adenomas and carcinomas is consistent with a polycryptal model derived from multiple independent initiation linages as the source of early ITH in colorectal carcinogenesis.

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Combined BTK and PI3K{delta} inhibition with acalabrutinib and ACP-319 improves survival and tumor control in CLL mouse model

Purpose: Targeting the B-cell receptor (BCR) pathway with inhibitors of BTK and PI3K-delta is highly effective for the treatment of chronic lymphocytic leukemia (CLL). However, deep remissions are uncommon and drug resistance with single-agent therapy can occur. In vitro studies support the effectiveness of combing PI3K-delta and BTK inhibitors. <p>Experimental design: As CLL proliferation and survival depends on the microenvironment, we used murine models to assess the efficacy of the BTK inhibitor acalabrutinib combined with the PI3K-delta inhibitor ACP-319 in vivo. We compared single-agent with combination therapy in TCL1-192 cell-injected mice, a model of aggressive CLL.</p> <p>Results: We found significantly larger reductions in tumor burden in the peripheral blood and spleen of combination-treated mice. While single-agent therapy improved survival compared with control mice by a few days, combination therapy extended survival by over two weeks compared to either single agent. The combination reduced tumor proliferation, NF-KB signaling and expression of BCL-xL and MCL-1 more potently than single-agent therapy.</p> <p>Conclusion: The combination of acalabrutinib and ACP-319 was superior to single-agent treatment in a murine CLL model, warranting further investigation of this combination in clinical studies.

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T cell receptors for clinical therapy: in vitro assessment of toxicity risk

Adoptive therapy with T cell receptor (TCR)-engineered T cells has shown promising results in the treatment of patients with tumors, and the number of TCRs amenable for clinical testing is expanding rapidly. Notably, adoptive therapy with T cells is challenged by treatment-related side effects, which calls for cautious selection of target antigens and TCRs that goes beyond their mere ability to induce high T cell reactivity. Here, we propose a sequence of in vitro assays to improve selection of TCRs, and exemplify risk assessments of on-target as well as off-target toxicities using TCRs directed against Cancer Germline Antigens. The proposed panel of assays covers parameters considered key to safety, such as expression of target antigen in healthy tissues, determination of a TCR's recognition motif towards its cognate peptide, and TCR's cross-reactivity towards non-cognate peptides.

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Disease-specific hematopoietic stem cell transplantation in children with inherited bone marrow failure syndromes

Abstract

Hematopoietic stem cell transplantation (HSCT) using an optimized conditioning regimen is essential for the long-term survival of patients with inherited bone marrow failure syndromes (IBMFS). We report HSCT in 24 children with Fanconi anemia (FA, n = 12), Diamond–Blackfan anemia (DBA, n = 7), and dyskeratosis congenita (DC, n = 5) from a single HSCT center. The graft source was peripheral blood stem cells (n = 19) or cord blood stem cells (n = 5). FA and DC patients received reduced-intensity conditioning, while DBA patients had myeloablative conditioning. The median numbers of infused mononuclear cells and CD34+ cells were 14.20 × 10⁸/kg and 4.3 × 10⁶/kg, respectively. The median time for neutrophil and platelet recovery was 12 and 18 days, respectively. Complete donor engraftment was achieved in 23 of 24 patients. There was one primary graft failure. During a median follow-up of 27.5 months (range, 2–130 months), the overall survival in all patients was 95.8%. The incidence of grade II–III acute graft versus host disease (GvHD) and chronic GvHD was 29.2% and 16.7%, respectively. We conclude that HSCT can be a curative option for patients with IBMFS. Modification of the conditioning regimen based on the type of disease may lead to encouraging long-term outcomes.

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Rethinking the usefulness of bone marrow biopsy on treatment decision in CLL patients at diagnosis

Abstract

We aimed to investigate the role of bone marrow infiltration pattern (BMIP) and bone marrow reticulin fibrosis (BMRF) in determining treatment demand in patients with diagnosis of chronic lymphocytic leukemia (CLL). We retrospectively evaluated the data of 65 patients, who were followed with the diagnosis of CLL at Istanbul Training and Research Hospital, Department of Hematology, between July 2007 and June 2016. The median age of the patients was 64 years (range, 32–83). Twenty-three (35.4%) patients were female, and 42 (64.6%) were male. Early/mild grade BMRF was observed in 46 (70.8%) patients and advanced grade BMRF in 19 (29.2%) patients. Eleven (23.9%) of 46 patients with early/mild grade BMRF and 10 (52.9%) of 19 patients with advanced grade BMRF required treatment during follow-up (p = 0.04). According to the BMIP, 14 (21.5%) patients had diffuse and 51 (78.5%) patients had non-diffuse BMIP. Eleven (78.6%) of 14 patients with diffuse BMIP and 10 (19.6%) of 51 patients with non-diffuse BMIP required treatment during follow-up (p < 0.001). In univariate analysis, both advanced grade BMRF and diffuse BMIP had an impact on occurrence of treatment demand (p = 0.028, HR = 3.535 vs. p < 0.01 HR = 15.033). Multivariate analysis also revealed diffuse BMIP to be effective (p < 0.001, HR 13.089), while advanced grade BMRF failed to significantly influence treatment demand (p = 0.140, HR 2.664). In conclusion, in the light of our findings, it is reasonable to consider that bone marrow biopsy at the time of diagnosis might provide a preliminary information about treatment demand in patients with CLL.

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Successful treatment with azacitidine for the simultaneous occurrence of multiple myeloma and acute myeloid leukemia with concomitant del(5q) and the JAK2 V617F mutation

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Vitamin D and plasma cell dyscrasias: reviewing the significance

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is a clonal plasma cell disorder and precursor disease to multiple myeloma and other related cancers. While MGUS is considered a benign disorder, with a low risk of disease progression, patients have altered bone microarchitecture and an increased risk of bone fracture. In addition, alterations in immune function are regularly found to correlate with disease activity. Vitamin D, an important hormone for bone and immune health, is commonly deficient in multiple myeloma patients. However, vitamin D deficiency is also prevalent in the general population. The purpose of this review is to highlight the current understanding of vitamin D in health and disease and to parallel this with a review of the abnormalities found in plasma cell dyscrasias. While some consensus statements have advocated for vitamin D testing and routine supplementation in MGUS, there is no clear standard of care approach and clinical practice patterns vary. Further research is needed to better understand how vitamin D influences outcomes in MGUS patients.

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Sweet syndrome secondary to myelodysplastic syndrome mimicking necrotizing fasciitis

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Central nervous system involvement in adults with haemophagocytic lymphohistiocytosis: a single-center study

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem disorder characterized by proliferation and diffuse infiltration multiple organs with histiocytes, including the central nervous system (CNS). Neurological manifestations of HLH have been recognized in different studies with children, but they remain relatively ill-defined in adults with HLH. From March 2008 to October 2014, 289 adult patients with HLH were admitted to our center. Clinical, radiological, and cerebral spinal fluid (CSF) data of the patients with CNS involvement were reviewed, and a retrospective study in our single-center was carried out. CNS involvement was observed in 29 patients (10%) either in their diagnosis process or during disease course. CNS symptoms included disturbance of consciousness, cranial nerve palsies, seizures, headache, limb paralysis, irritability, meningism, and memory loss. CSF analysis was conducted in 17 patients (59%). Among them, 11 patients (65%) were reported as having abnormal CSF. Neuroradiological studies were performed in 25 patients (86%). Among the 13 cases that underwent CT scan, one patient hemorrhaged. Single or multiple hypodense foci were detected in the other 2 patients. Magnetic resonance imaging (MRI) abnormalities were found in 15 patients, including focal lesions in cortical and adjacent subcortical regions with or without variable nodular or ring contrast-enhancement, multiple lesions in white matter, diffuse white matter signal changes, and meningeal enhancement. Basal ganglia, cerebellum, and brainstem lesions were also observed. CNS involvement could also be found in adult patients with HLH, but not as frequent as it was in children. The clinical manifestations could be diversified. By carrying out rigorous CNS examinations, an early diagnosis could be made and it was of the utmost importance for the prevention of further lesions.

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Co-mutated CALR and MPL driver genes in a patient with myeloproliferative neoplasm

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Pathogen reduction/inactivation of products for the treatment of bleeding disorders: what are the processes and what should we say to patients?

Abstract

Patients with blood disorders (including leukaemia, platelet function disorders and coagulation factor deficiencies) or acute bleeding receive blood-derived products, such as red blood cells, platelet concentrates and plasma-derived products. Although the risk of pathogen contamination of blood products has fallen considerably over the past three decades, contamination is still a topic of concern. In order to counsel patients and obtain informed consent before transfusion, physicians are required to keep up to date with current knowledge on residual risk of pathogen transmission and methods of pathogen removal/inactivation. Here, we describe pathogens relevant to transfusion of blood products and discuss contemporary pathogen removal/inactivation procedures, as well as the potential risks associated with these products: the risk of contamination by infectious agents varies according to blood product/region, and there is a fine line between adequate inactivation and functional impairment of the product. The cost implications of implementing pathogen inactivation technology are also considered.

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Co-occurrence of type I CALR and two MPL mutations in patient with primary myelofibrosis

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Influence of TNF and IL6 gene polymorphisms on the severity of cytopenias in Argentine patients with myelodysplastic syndromes

Abstract

Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematologic disorders characterized by cytopenia(s) and predisposition to leukemic progression. An immune dysregulation and an aberrant bone marrow microenvironment seem to be key elements in the physiopathological process of MDS. In order to evaluate a possible association between susceptibility and clinic-pathologic features, we genotyped 153 MDS patients for functional cytokine polymorphisms: TNF (−308 G/A), IFNG (+874 A/T and +875 CAn), IL6 (−174 G/C), and TGFB1 (+869 C/T and +915 G/C). The frequency of TNF and IL6 polymorphisms was different between patients and healthy controls (n = 131), suggesting a relatedness to MDS susceptibility in our population. Furthermore, the presence of each or both high-producing genotypes [TNF: p = 0.048, odds ratio (OR): 3.979; IL6: p = 0.001, OR: 6.835; both: p = 0.010, OR: 6.068] and thrombocytopenia at platelet counts of <50,000/μL (p = 0.004, OR: 4.857) were independently associated with an increased risk of manifesting a hemoglobin level of <8 g/dL at diagnosis. In particular, a severe bicytopenia was more frequently observed in patients with the TNF (high)_IL6 (high) combined genotype (p = 0.004, OR: 8.357), who consistently became transfusion dependent earlier (2.9 vs. 34.6 months; p = 0.001); and this likelihood was more evident in patients with lower bone marrow blast counts. The contribution of the remaining functional polymorphisms to the disease phenotype was less relevant. Our results demonstrate that TNF and IL6 gene polymorphisms, as underlying host features, are likely to play a key role in influencing the severity of the cytopenias in MDS and they may be instrumental for tailoring cytokine-target therapies.

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Serum EBV EA-IgA and VCA-IgA antibodies can be used for risk group stratification and prognostic prediction in extranodal NK/T cell lymphoma: 24-year experience at a single institution

Abstract

Although extranodal NK/T cell lymphoma (ENKTCL) is consistently associated with Epstein-Barr virus (EBV) infection, the manifestation and prognostic value of serum EBV antibodies still remain unknown. One hundred and forty-one patients with ENKTCL were evaluated for serum EBV EA-IgA and VCA-IgA antibodies levels in the past 24 years in our institution. Their correlation with clinicopathological features, plasma EBV DNA load, and patients' outcomes was analyzed. EBV EA-IgA ≥1:10 and VCA-IgA ≥1:160 were found in 18.4 and 16.3% of patients, respectively. They correlated with adverse ENKTCL profile and inferior overall survival (OS) and progression-free survival (PFS). EA-IgA ≥1:10 was an independent prognostic factor on OS (RR = 2.276, p = 0.008) and associated with lower complete response (CR) rate (34.8 vs 70.6%, p = 0.001) and higher relapse rate in CR patients (62.5 vs 34.7%, p = 0.016). In subgroup analysis, both EA-IgA ≥1:10 and VCA-IgA ≥1:160 significantly correlated with inferior OS and PFS in patients with stage I/II, IPI score 0–1, plasma EBV DNA (+), and CR. Patients with plasma EBV DNA (+) and EA-IgA ≥1:10 (or VCA-IgA ≥1:160) had significantly shorter periods of OS and PFS in comparison with other corresponding groups. Elevated serum EBV EA-IgA and VCA-IgA levels were related to adverse ENKTCL profile and correlated with poor treatment response, early relapse, and poor prognosis in patients with ENKTCL. These findings provide convincing evidence for the use of serum EBV EA-IgA and VCA-IgA antibodies for risk group stratification and prognostic prediction in ENKTCL.

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NF1+/- hematopoietic cells accelerate malignant peripheral nerve sheath tumor development without altering chemotherapy response

Haploinsufficiency in the tumor suppressor NF1 contributes to the pathobiology of type 1 neurofibromatosis, but a related role has not been established in malignant peripheral nerve sheath tumors (MPNST) where NF1 mutations also occur. Patients with NF1-associated MPNST appear to have worse outcomes than patients with sporadic MPNST, but the mechanism underlying this correlation is not understood. To define the impact of stromal genetics on the biology of this malignancy, we developed unique mouse models that reflect the genetics of patient-associated MPNST. Specifically, we used adenovirus-cre injections to generate MPNST in Nf1 Flox/Flox ; Ink4a/Arf Flox/Flox and Nf1 Flox/- ; Ink4a/Arf Flox/Flox paired littermate mice to model tumors from NF1-wildtype and NF1-associated patients, respectively. In these models, Nf1 haploinsufficiency in hematopoietic cells accelerated tumor onset and increased levels of tumor-infiltrating immune cells comprised of CD11b+ cells, monocytes and mast cells. We observed that mast cells were also enriched in human NF1-associated MPNST. In a co-clinical trial to examine how the tumor microenvironment influences the response to multi-agent chemotherapy, we found that stromal Nf1 status had no effect. Taken together, our results clarify the role of the NF1-haploinsufficient tumor microenvironment in MPNST.

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Predicting Indirect Effects of Predator–Prey Interactions

Synopsis

Predicting the effects of climate change on species and communities remains a pre-eminent challenge for biologists. Critical among this is understanding the indirect effects of climate change, which arise when the direct, physiological effects of climate on one species change the outcome of its interaction with a second species, altering the success of the second species. A diverse array of approaches to predicting indirect effects exists from mechanistic models, which attempt to build-up from physiological changes to ecological consequences, to ecological models that focus solely on the ecological scale. Here I review studies of the indirect effects of temperature on two predator–prey systems in rocky intertidal habitats. Laboratory and field studies have shown that temperature can indirectly affect interactions through both physiological and behavioral changes in predator and prey, but no model yet captures the full range of these effects. The three main categories of changes are metabolic rate effects, stress effects, and behavioral avoidance. Mechanistic models best capture the first two of these three dynamics, while ecological models have focused mainly on the last two. The challenge remains to correctly identify a species' vulnerability to climate change, which differs from its physiological sensitivity. The best approach may be to use detailed physiological-scale studies of indirect effect in a few systems to ground truth simpler models that can be applied more broadly. Model development and testing is also hampered by the small number of field studies of indirect effects in natural systems, particularly studies that examine natural temporal or spatial variation in climate.

http://ift.tt/2tEl2IC

Diversity and Persistence of the Gut Microbiome of the Giant Neotropical Bullet Ant

Synopsis

Identifying the factors that structure host-associated microbiota is critical to understand the role these microbes may play in host ecology and evolutionary history. To begin to address this question we investigate the diversity and persistence of the bacterial community of the giant Neotropical bullet ant, Paraponera clavata. We included samples from four widely dispersed locations to address the role geography plays in shaping these communities. To understand how the digestive tract can filter bacterial communities, we sampled mouth and gut communities. To investigate the stability of community members we sampled wild caught and individuals kept on a sterile diet. Only a single bacterial taxon in the Firmicutes is consistently present across individuals, indicating a remarkably simple "core" bacterial community for the giant Neotropical bullet ant. Geography did not explain host bacterial diversity, but we did find significant reductions in diversity between the mouth and the gut tract. Lastly, our diet manipulations highlight the importance of controlled experiments to tease apart persistent microbial communities from environmental transients.

http://ift.tt/2t4DRrg

Amlexanox downregulates S100A6 to sensitize KMT2A/AFF1-positive acute lymphoblastic leukemia to TNF-{alpha} treatment

Acute lymphoblastic leukemias (ALL) positive for KMT2A/AFF1 (MLL/AF4) translocation, which constitute 60% of all infant ALL cases, have a poor prognosis even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This poor prognosis is due to one of two factors, either resistance to TNF-α which mediates a graft-versus-leukemia (GVL) response after allo-HSCT, or immune resistance due to upregulated expression of the immune escape factor S100A6. Here we report an immune stimulatory effect against KMT2A/AFF1-positive ALL cells by treatment with the anti-allergy drug amlexanox, which we found to inhibit S100A6 expression in the presence of TNF-α. In KMT2A/AFF1-positive transgenic (Tg) mice, amlexanox enhanced tumor immunity and lowered the penetrance of leukemia development. Similarly, in a NOD/SCID mouse model of human KMT2A/AFF1-positive ALL, amlexanox broadened GVL responses and extended survival. Our findings show how amlexanox degrades the resistance of KMT2A/AFF1-positive ALL to TNF-α by downregulating S100A6 expression, with immediate potential implications for improving clinical management of KMT2A/AFF1-positive ALL.

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MCAM mediates chemoresistance in small cell lung cancer via the PI3K/AKT/SOX2 signaling pathway

Despite favorable responses to initial therapy, small cell lung cancer (SCLC) relapse occurs within a year and exhibits resistance to multiple drugs. Due to limited accessibility of patient tissues for research purposes, SCLC-patient derived xenografts (PDX) have provided the best opportunity to address this limitation. Here we sought to identify novel mechanisms involved in SCLC chemoresistance. Through in-depth proteomic profiling, we identified MCAM as a markedly upregulated surface receptor in chemoresistant SCLC cell lines and in chemoresistant PDX compared to matched treatment-naïve tumors. MCAM depletion in chemoresistant cells reduced cell proliferation and reduced the IC50 inhibitory concentration of chemotherapeutic drugs in vitro. This MCAM-mediated sensitization to chemotherapy occurred via SOX2-dependent upregulation of mitochondrial 37S ribosomal protein 1/ATP binding cassette subfamily C member 1 (MRP1/ABCC1) and the PI3/AKT pathway. Metabolomic profiling revealed that MCAM modulated lactate production in chemoresistant cells that exhibit a distinct metabolic phenotype characterized by low oxidative phosphorylation. Our results suggest that MCAM may serve as a novel therapeutic target to overcome chemoresistance in SCLC.

http://ift.tt/2sAKUq9

EIF1AX and NRAS mutations co-occur and cooperate in low-grade serous ovarian carcinomas

Low-grade serous ovarian carcinomas (LGSC) are associated with a poor response to chemotherapy and are molecularly characterized by RAS pathway activation. Using exome and whole genome sequencing we identified recurrent mutations in the protein translational regulator EIF1AX and in NF1, USP9X, KRAS, BRAF and NRAS. RAS pathway mutations were mutually exclusive, however we found significant co-occurrence of mutations in NRAS and EIF1AX. Missense EIF1AX mutations were clustered at the N-terminus of the protein in a region associated with its role in ensuring translational initiation fidelity. Co-expression of mutant NRAS and EIF1AX proteins promoted proliferation and clonogenic survival in LGSC cells, providing the first example of co-occurring, growth-promoting mutational events in ovarian cancer.

http://ift.tt/2s5LybN

Functionally null RAD51D missense mutation associates strongly with ovarian carcinoma

RAD51D is a key player in DNA repair by homologous recombination (HR) and RAD51D truncating mutation carriers have an increased risk for ovarian cancer (OC). However, the contribution of non-truncating RAD51D variants to cancer predisposition remains uncertain. Using deep sequencing and case-control genotyping studies, we show that in French Canadians, the missense RAD51D variant c.620C>T;p.S207L is highly prevalent and is associated with a high risk for ovarian high-grade serous carcinoma (HGSC) (3.8% cases vs 0.2% controls). The frequency of the p.S207L variant did not significantly differ from that of controls in breast, endometrial, pancreas or colorectal adenocarcinomas. Functionally, we show for the first time that this mutation impairs HR by disrupting the RAD51D-XRCC2 interaction and confers PARP-inhibitor sensitivity. These results highlight the importance of a functional RAD51D-XRCC2 interaction to promote HR and prevent the development of HGSC. This study identifies c.620C>T;p.S207L as the first bona fide pathogenic RAD51D missense cancer susceptibility allele and supports the use of targeted PARP-inhibitor therapies in OC patients carrying deleterious missense RAD51D mutations.

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FUT8 Promotes Melanoma Invasion and Metastasis [Research Watch]

FUT8-mediated core fucosylation of L1CAM drives melanoma metastasis.

http://ift.tt/2s5Kwwq

ERF Competes with ERG for Chromatin Binding to Control Oncogenesis [Research Watch]

In prostate cancer, ERF loss-of-function mutations enhance ERG activity to promote tumorigenesis.

http://ift.tt/2sAzXVD

Epigenetic Drugs Promote Transcription from Cryptic Start Sites [Research Watch]

HDAC and DNMT inhibitors promoted global de novo transcription from nonannotated TSSs (termed TINAT).

http://ift.tt/2s5yALb

MLL2 Promotes Cell Survival in MLL1-Rearranged Acute Myeloid Leukemia [Research Watch]

Loss of MLL2, but not MLL1, suppresses MLL1-rearranged acute myeloid leukemia.

http://ift.tt/2sAgzIo

A Click-Chemistry Approach Reveals the BET Inhibitor Mechanism of Action [Research Watch]

Click chemistry–based modification of BET inhibitors allows use as molecular probes in vitro and in vivo.

http://ift.tt/2s5T5ap

Hyperbaric oxygen may only be optional in head and neck necrotizing fasciitis: a retrospective analysis of 43 cases and review of the literature

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http://ift.tt/2s1cdLy

Predictive biomarkers for triple negative breast cancer treated with platinum-based chemotherapy

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http://ift.tt/2rMcNsC

CRISPR/Cas9-based Pten knock-out and Sleeping Beauty Transposon-mediated Nras knock-in induces hepatocellular carcinoma and hepatic lipid accumulation in mice

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http://ift.tt/2t4SVor

Zinc oxide nanoparticles antagonize the effect of Cetuximab on head and neck squamous cell carcinoma in vitro

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http://ift.tt/2t4HkFU

Depletion of signal recognition particle 72kDa increases radiosensitivity

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http://ift.tt/2rMeDcO

Functional analysis of rare variants in mismatch repair proteins augments results from computation-based predictive methods

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http://ift.tt/2rMa4zn

Diagnosis, staging, and risk stratification in prostate cancer: Utilizing diagnostic tools to avoid unnecessary therapies and side effects

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http://ift.tt/2t4VTJD

Succinylcholine Chloride 20mg/mL 5mL Syringe by Fagron Sterile Services: Recall - Potential Lack Of Sterility Assurance

Audience: Pharmacy, Critical Care Medicine [Posted 06/23/2017] ISSUE: Fagron Sterile Services is voluntarily recalling three (3) lots of Succinylcholine Chloride 20mg/mL 5mL syringe to the hospital/clinic level. The secondary recall of product...

http://ift.tt/2tYbzLz

10th Oxford Debate

Janet Bezner, PT, DPT, PhD, FAPTA, and Scott Euype, PT, DPT, MHS, recap the 2017 Oxford Debate, "Jack of All vs. Master of One," which playfully argued whether PTs and PTAs should demonstrate expertise in a specific focused area of practice immediately upon graduation.

https://www.youtube.com/watch?v=ScBcLvHiFA4

22nd John H.P. Maley Lecture

Tara Jo Manal, PT, DPT, FAPTA, discusses her lecture "Strike While the Iron is Hot," delivered at NEXT 2017.

https://www.youtube.com/watch?v=XeuPh3XrHc4

#APTAvalue: Financial Solutions Center

Discussing the newest APTA benefit, the Financial Solutions Center. Representatives from Enrich and Laurel Road talk about how APTA members can explore personalized online financial education tools and student loan refinancing.

https://www.youtube.com/watch?v=YPIujaAML94

Enabling Young Leaders

Massachusetts Chapter President Heather Jennings, PT, DPT, discusses her development as a young leader, and how that development was supported by older generations.

https://www.youtube.com/watch?v=aCtINssgJTo

Foundation for Physical Therapy VCU-Marquette Challenge

Foundation for Physical Therapy VCU-Marquette Challenge announcement of 2017 winning school.

https://www.youtube.com/watch?v=uCBKdT4UGAc

Utilization of acid pre-treated coconut dregs as a substrate for production of detergent compatible lipase by Bacillus stratosphericus

In recent years, many efforts have been directed to explore the methods to reduce the production costs of industrial lipase by improving the yield and the use of low-cost agricultural wastes. Coconut dregs, wh...

http://ift.tt/2sLkBvX

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

New England Journal of Medicine, Ahead of Print.


http://ift.tt/2rLBQMj

Succinylcholine Chloride 20mg/mL 5mL Syringe by Fagron Sterile Services: Recall - Potential Lack Of Sterility Assurance

Audience: Pharmacy, Critical Care Medicine [Posted 06/23/2017] ISSUE: Fagron Sterile Services is voluntarily recalling three (3) lots of Succinylcholine Chloride 20mg/mL 5mL syringe to the hospital/clinic level. The secondary recall of product...

http://ift.tt/2tYbzLz

No additional prognostic value for MRE11 in squamous cell carcinomas of the anus treated with chemo-radiotherapy

No additional prognostic value for MRE11 in squamous cell carcinomas of the anus treated with chemo-radiotherapy

British Journal of Cancer advance online publication, June 22 2017. doi:10.1038/bjc.2017.188

Authors: Alexandra K Walker, Christiana Kartsonaki, Elena Collantes, Judith Nicholson, Duncan C Gilbert & Anne E Kiltie

http://ift.tt/2tzuCwr

Comment on 'The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis'

Comment on 'The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis'

British Journal of Cancer advance online publication, June 22 2017. doi:10.1038/bjc.2017.184

Author: Alain Braillon

http://ift.tt/2tzFtX0

A cancer geography paradox? Poorer cancer outcomes with longer travelling times to healthcare facilities despite prompter diagnosis and treatment: a data-linkage study

A cancer geography paradox? Poorer cancer outcomes with longer travelling times to healthcare facilities despite prompter diagnosis and treatment: a data-linkage study

British Journal of Cancer advance online publication, June 22 2017. doi:10.1038/bjc.2017.180

Authors: Melanie Turner, Shona Fielding, Yuhan Ong, Chris Dibben, Zhiqianq Feng, David H Brewster, Corri Black, Amanda Lee & Peter Murchie

http://ift.tt/2t0thBM

Characterisation of blood-derived exosomal hTERT mRNA secretion in cancer patients: a potential pan-cancer marker

Characterisation of blood-derived exosomal hTERT mRNA secretion in cancer patients: a potential pan-cancer marker

British Journal of Cancer advance online publication, June 22 2017. doi:10.1038/bjc.2017.166

Authors: Hadar Goldvaser, Anna Gutkin, Einat Beery, Yonatan Edel, Jardena Nordenberg, Ofir Wolach, Ester Rabizadeh, Orit Uziel & Meir Lahav

http://ift.tt/2tzLdjH

Human equilibrative nucleoside transporter 1 gene expression is associated with gemcitabine efficacy in advanced leiomyosarcoma and angiosarcoma

Human equilibrative nucleoside transporter 1 gene expression is associated with gemcitabine efficacy in advanced leiomyosarcoma and angiosarcoma

British Journal of Cancer advance online publication, June 22 2017. doi:10.1038/bjc.2017.187

Authors: Bruno Vincenzi, Silvia Stacchiotti, Paola Collini, Francesco Pantano, Carla Rabitti, Giuseppe Perrone, Michele Iuliani, Alfonso Baldi, Giuseppe Badalamenti, Roberta Sanfilippo, Daniele Santini, Andrea Onetti Muda, Alessandro Gronchi, Paolo Casali, Angelo Paolo Dei Tos & Giuseppe Tonini

http://ift.tt/2t0oYGF

Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy

Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy

British Journal of Cancer advance online publication, June 22 2017. doi:10.1038/bjc.2017.175

Authors: K J Gash, A C Chambers, D E Cotton, A C Williams & M G Thomas

http://ift.tt/2tzQKqh

Detection of phosphatidylserine-positive exosomes for the diagnosis of early-stage malignancies

Detection of phosphatidylserine-positive exosomes for the diagnosis of early-stage malignancies

British Journal of Cancer advance online publication, June 22 2017. doi:10.1038/bjc.2017.183

Authors: Raghava Sharma, Xianming Huang, Rolf A Brekken & Alan J Schroit

http://ift.tt/2t0a3fv

Sequential versus concurrent chemotherapy for adjuvant breast cancer: does dose intensity matter?

Sequential versus concurrent chemotherapy for adjuvant breast cancer: does dose intensity matter?

British Journal of Cancer advance online publication, June 22 2017. doi:10.1038/bjc.2017.176

Authors: N LeVasseur & S K Chia

http://ift.tt/2tzPoMc

Reply to ‘Comment on ‘The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis’’

Reply to 'Comment on 'The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis''

British Journal of Cancer advance online publication, June 22 2017. doi:10.1038/bjc.2017.185

Authors: L Zgaga, P G Vaughan-Shaw, F O'Sullivan, S M Farrington, E Theodoratou, H Campbell & M G Dunlop

http://ift.tt/2t0etTA

Impact of novel miR-145-3p regulatory networks on survival in patients with castration-resistant prostate cancer

Impact of novel miR-145-3p regulatory networks on survival in patients with castration-resistant prostate cancer

British Journal of Cancer advance online publication, June 22 2017. doi:10.1038/bjc.2017.191

Authors: Yusuke Goto, Akira Kurozumi, Takayuki Arai, Nijiro Nohata, Satoko Kojima, Atsushi Okato, Mayuko Kato, Kazuto Yamazaki, Yasuo Ishida, Yukio Naya, Tomohiko Ichikawa & Naohiko Seki

http://ift.tt/2t00wFb

Evaluation of serum microRNA biomarkers for gastric cancer based on blood and tissue pools profiling: the importance of miR-21 and miR-331

Evaluation of serum microRNA biomarkers for gastric cancer based on blood and tissue pools profiling: the importance of miR-21 and miR-331

British Journal of Cancer advance online publication, June 22 2017. doi:10.1038/bjc.2017.190

Authors: Marek Sierzega, Marcin Kaczor, Piotr Kolodziejczyk, Jan Kulig, Marek Sanak & Piotr Richter

http://ift.tt/2tA4zVK

Sequential vs concurrent epirubicin and docetaxel as adjuvant chemotherapy for high-risk, node-negative, early breast cancer: an interim analysis of a randomised phase III study from the Hellenic Oncology Research Group

Sequential vs concurrent epirubicin and docetaxel as adjuvant chemotherapy for high-risk, node-negative, early breast cancer: an interim analysis of a randomised phase III study from the Hellenic Oncology Research Group

British Journal of Cancer advance online publication, June 22 2017. doi:10.1038/bjc.2017.158

Authors: Dimitrios Mavroudis, Emmanouil Saloustros, Ioannis Boukovinas, Pavlos Papakotoulas, Stylianos Kakolyris, Nikolaos Ziras, Charalampos Christophylakis, Nikolaos Kentepozidis, Georgios Fountzilas, Georgios Rigas, Ioannis Varthalitis, Konstantinos Kalbakis, Sofia Agelaki, Dora Hatzidaki & Vasilios Georgoulias

http://ift.tt/2t0HU7U

Nephrotic Syndrome With Cancer Immunotherapies: A Report of 2 Cases

Oncologic immunotherapies use a patient's immune response to eliminate tumor cells by modulation of immune checkpoints, including programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) proteins. Immune-mediated sequelae, including interstitial nephritis, have been reported; however, glomerular disease appears rare. We describe 2 cases of nephrotic syndrome in patients treated with these agents. Patient 1 received the anti–PD-1 antibody pembrolizumab for Hodgkin lymphoma.

http://ift.tt/2t4FCEC

Risk of ESRD and Mortality Associated With Change in Filtration Markers

Using change in estimated glomerular filtration rate (eGFR) based on creatinine concentration as a surrogate outcome in clinical trials of chronic kidney disease has been proposed. Risk for end-stage renal disease (ESRD) and all-cause mortality associated with change in concentrations of other filtration markers has not been studied in chronic kidney disease populations.

http://ift.tt/2t4FDIG

Associations of Early Kidney Disease With Brain Magnetic Resonance Imaging and Cognitive Function in African Americans With Type 2 Diabetes Mellitus

Relationships between early kidney disease, neurocognitive function, and brain anatomy are poorly defined in African Americans with type 2 diabetes mellitus (T2DM).

http://ift.tt/2rLSH1F

Are Children Born with Birth Defects at Increased Risk of Injuries in Early Childhood?

To investigate the extent to which children with birth defects experience differential likelihood of various injuries and injury-related hospitalizations in early childhood.

http://ift.tt/2s14H3p

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

New England Journal of Medicine, Ahead of Print.


http://ift.tt/2rLBQMj

Special Issue on Medical Art Therapy

Volume 34, Issue 2, April 2017, Page 99-99
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Research Scholarship in Art Therapy: What Should Come Next?

Volume 34, Issue 2, April 2017, Page 56-57
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http://ift.tt/2rLHEFy

A case report of thoracolumbar paraspinal myopathy as the cause of camptocormia in a patient with atypical parkinsonism

Camptocormia is severe flexion of the thoracolumbar spine, exaggerated during standing and walking but minimized in supine position. Even though camptocormia is a relatively common condition during the course ...

http://ift.tt/2s50nv5

How Often Is Hearing Loss Considered?

As audiologists, we know firsthand the impact that hearing loss has on communication. Before we begin speaking, we look at our patients and provide an unobstructed view of our face. As soon as patients walk into our office, we adjust the volume, pitch, and tempo of our speech to ensure that they can hear and understand us. We hope that other health-care providers, including physicians, are also attuned to their patients' hearing needs particularly when helping older adults where a prevalence of hearing loss is high.

Tweet

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ImageTrend Continuum™ named JEMS Hot Product at EMS Today 2017

LAKEVILLE, Minn. — ImageTrend, Inc. announced Continuum, the company's Active Data Monitoring™ solution, has been selected as a JEMS Hot Product at EMS Today 2017. The solution was designed to deliver information when, where and how agencies want it for immediate response and care delivery improvement. Continuum ...

http://ift.tt/2s4ZUch

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

Acute myeloid leukemia (AML) is a heterogeneous disease that remains challenging to treat because of patient factors (age and coexisting diseases) and intrinsic biologic factors. Cytogenetic and mutational data are used to divide patients into subgroups defined according to prognostic factors and…

http://ift.tt/2tD4nVX

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

Acute myeloid leukemia (AML) is a heterogeneous disease that remains challenging to treat because of patient factors (age and coexisting diseases) and intrinsic biologic factors. Cytogenetic and mutational data are used to divide patients into subgroups defined according to prognostic factors and…

http://ift.tt/2tD4nVX

β-NGF and β-NGF receptor upregulation in blood and synovial fluid in osteoarthritis

Journal Name: Biological Chemistry
Issue: Ahead of print


http://ift.tt/2s0Gt9t

Shared function and moonlighting proteins in molybdenum cofactor biosynthesis

Journal Name: Biological Chemistry
Issue: Ahead of print


http://ift.tt/2sKruh9

S100A6 – focus on recent developments

Journal Name: Biological Chemistry
Issue: Ahead of print


http://ift.tt/2s0mTKB

The role of sirtuins in mitochondrial function and doxorubicin-induced cardiac dysfunction

Journal Name: Biological Chemistry
Issue: Ahead of print


http://ift.tt/2sKXxh7

Mutation of N-linked glycosylation in EpCAM affected cell adhesion in breast cancer cells

Journal Name: Biological Chemistry
Issue: Ahead of print


http://ift.tt/2s0vw7Q

The monoheme cytochrome c subunit of Alternative Complex III is a direct electron donor to caa3 oxygen reductase in Rhodothermus marinus

Journal Name: Biological Chemistry
Issue: Ahead of print


http://ift.tt/2sKIELr

Molecular challenges imposed by MHC-I restricted long epitopes on T cell immunity

Journal Name: Biological Chemistry
Issue: Ahead of print


http://ift.tt/2rZViJs

Iron overload and altered iron metabolism in ovarian cancer

Journal Name: Biological Chemistry
Issue: Ahead of print


http://ift.tt/2sKIFPv

In vitro modelling of familial amyloidotic polyneuropathy allows quantitative detection of transthyretin amyloid fibril-like structures in hepatic derivatives of patient-specific induced pluripotent stem cells

Journal Name: Biological Chemistry
Issue: Ahead of print


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Human papillomavirus first and second generation vaccines–current status and future directions

Journal Name: Biological Chemistry
Issue: Ahead of print


http://ift.tt/2sKBGWU

Scalable Solution-processed Fabrication Strategy for High-performance, Flexible, Transparent Electrodes with Embedded Metal Mesh

This protocol describes a solution-based fabrication strategy for high-performance, flexible, transparent electrodes with fully-embedded, thick metal mesh. Flexible transparent electrodes fabricated by this process demonstrate among the highest reported performances, including ultra-low sheet resistance, high optical transmittance, mechanical stability under bending, strong substrate adhesion, surface smoothness, and environmental stability.

http://ift.tt/2t0caPr

Preparation of Janus Particles and Alternating Current Electrokinetic Measurements with a Rapidly Fabricated Indium Tin Oxide Electrode Array

In this article, a simple method to prepare partially or fully coated metallic particles and to perform AC electrokinetic property measurements with a rapidly fabricated indium tin oxide (ITO) electrode array is demonstrated.

http://ift.tt/2t3UvqR

Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology

Abstract

Two hallmarks of chronic multiple sclerosis lesions are the absence of significant spontaneous remyelination and primary as well as secondary neurodegeneration. Both characteristics may be influenced by the presence of inhibitory factors preventing myelin and neuronal repair. We investigated the potential of antibodies against Nogo-A, a well-known inhibitory protein for neuronal growth and plasticity, to enhance neuronal regeneration and remyelination in two animal models of multiple sclerosis. We induced a targeted experimental autoimmune encephalomyelitis (EAE) lesion in the dorsal funiculus of the cervical spinal cord of adult rats resulting in a large drop of skilled forelimb motor functions. We subsequently observed improved recovery of forelimb function after anti-Nogo-A treatment. Anterograde tracing of the corticospinal tract revealed enhanced axonal sprouting and arborisation within the spinal cord gray matter preferentially targeting pre-motor and motor spinal cord laminae on lesion level and above in the anti-Nogo-A-treated animals. An important additional effect of Nogo-A-neutralization was enhanced remyelination observed after lysolecithin-induced demyelination of spinal tracts. Whereas remyelinated fiber numbers in the lesion site were increased several fold, no effect of Nogo-A-inhibition was observed on oligodendrocyte precursor proliferation, migration, or differentiation. Enhancing remyelination and promoting axonal regeneration and plasticity represent important unmet medical needs in multiple sclerosis. Anti-Nogo-A antibodies hold promise as a potential new therapy for multiple sclerosis, in particular during the chronic phase of the disease when neurodegeneration and remyelination failure determine disability evolution.

http://ift.tt/2tXzcnD

Immune-mediated effects targeting hepatitis C virus in a syngeneic replicon cell transplantation mouse model

Objective

HCV is characterised by its ability to establish chronic infection in hepatocytes and to replicate in the presence of an inflammation. We mimicked this situation in vivo in immune-competent mice by syngeneic transplantation of HCV replicon-containing mouse hepatoma cells.

Design

A total of 5 million H-2^b positive Hep56.1D cells, carrying a subgenomic genotype (gt) 2a replicon (HCV replicon cells) or stably expressing comparable levels of the HCV NS3/4A protease/helicase complex (NS3/4A hepatoma cells), were injected subcutaneously into syngeneic H-2^b-restricted mice. Kinetics of tumour growth, HCV RNA replication levels and HCV-specific immune responses were monitored. For immune monitoring, new H-2^b-restricted cytotoxic T cell epitopes within the gt2a NS3/4A region were mapped. Immune mice were generated by DNA-based vaccination.

Results

HCV replicon and NS3/4A hepatoma cells generated solid tumours in vivo. Similar to what is seen in human HCV infection did HCV RNA replicate in the presence of inflammation. NS3/4A-specific CD8+ T cells seemed to transiently reduce HCV RNA levels. Both CD4+ and CD8+ T cells were required for protection against tumour growth. Vaccine-induced NS3/4A(gt2a)-specific T cells protected against HCV replicon tumours in wild-type, but not in HCV NS3/4A(gt1a)-transgenic mice with dysfunctional HCV-specific T cells. Importantly, as in human HCV infection, HCV replicon cells neither primed nor boosted a strong NS3/4A-specific T cell response.

Conclusion

Syngeneic transplantation of mouse HCV replicon cells into immune-competent animals mirrors many in vivo events in humans. This system is versatile and can be applied to any genetically modified H-2^b-restricted mouse strain.

http://ift.tt/2rL2LYK

An audit on technical quality of root fillings performed by undergraduate students

Abstract

Aim

To evaluate radiographically the technical quality of root fillings performed by undergraduate dental students and to assess whether students were exposed to an appropriate endodontic case mix during their clinical training.

Methodology

A retrospective audit was undertaken evaluating the clinical records of patients who underwent endodontic procedures during the period from September 2015 to June 2016 in the Dental School at Queen's University Belfast, UK. Two final year dental students were trained and calibrated to evaluate post-operative intraoral periapical radiograph of completed root canal treatments using specific assessment criteria. Data was presented as frequencies, percentage and mean ± standard deviation (SD). Comparisons of treatment outcomes between groups (posterior and anterior teeth) were calculated using Fisher's Exact Test and the level of significance was set at p<0.05. Intra- and inter-examiner reproducibility was assessed by Kappa statistics.

Results

A total of 222 teeth and 381 canals were assessed and of those 253 (66%) of the root fillings were found to be acceptable in all the assessment parameters namely, taper, length and lateral adaptation of the root filling. Sub-analysis of individual root filling parameters revealed that 372 canals (97%) exhibited good taper, 275 canals (72%) were considered to be of an appropriate length, with 89 canals (23%) found to be underfilled and 17 canals (5%) overfilled. Overall 346 (91%) of canals had good lateral condensation. Students treated both single and multi-rooted teeth and there was no significant association between tooth type and the quality of root filling provided (p>0.05).

Conclusion

In the majority of the teeth treated by undergraduate students at Queen's University Belfast, the technical quality of the root filling was acceptable and students were exposed to an appropriate case mix for endodontic training.

This article is protected by copyright. All rights reserved.

http://ift.tt/2rL3pFF

An All-on-chip Method for Rapid Neutrophil Chemotaxis Analysis Directly from a Drop of Blood

This article provides the detailed method of performing a rapid neutrophil chemotaxis assay by integrating the on-chip neutrophil isolation from whole blood and the chemotaxis test on a single microfluidic chip.

http://ift.tt/2sZLBtE

Implementation of tobacco cessation brief intervention in complementary and alternative medicine practice: qualitative evaluation

This article presents findings from qualitative interviews conducted as part of a research study that trained Acupuncture, Massage, and Chiropractic practitioners' in Arizona, US, to implement evidence-based t...

http://ift.tt/2sZDzkL

3,5,4′-trihydroxy-6,7,3′-trimethoxyflavone protects against beta amyloid-induced neurotoxicity through antioxidative activity and interference with cell signaling

Alzheimer's disease is a neurodegenerative disease, characterized by progressive decline in memory and cognitive functions, that results from loss of neurons in the brain. Amyloid beta (Aβ) protein and oxidati...

http://ift.tt/2tXqMMR

Epigallocatechin gallate inhibits the type III secretion system of gram negative enteropathogenic bacteria under model condition

Abstract

Epigallocatechin gallate (EGCG), a major polyphenol in green tea, inhibits the type III secretion system (T3SS) of enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC, respectively), Salmonella enterica serovar Typhimurium, and Yersinia pseudotuberculosis. The inhibitory effect causes the inhibition of hemolysis, cell invasion, cell adhesion, and apoptosis, which are functions of the type III secretion device. In the case of EPEC, EspB accumulates in the cells. RT-PCR showed that the translation of EspB was not blocked. The transcription of escN, which supplies energy for the injection of the effector factor into the host cells, was also not inhibited. EGCG does not suppress the transcription and translation of T3SS constitutive protein in bacterial cells, but it seems to suppress the normal construction or secretion of T3SS. When LB medium was used to visualize the EGCG-induced inhibition of T3SS, the inhibitory effect disappeared. The inhibition of T3SS was partially canceled when the T3SS inhibitory potency of EGCG was examined by adding yeast extract, which is a component of LB medium, to DMEM. These results suggest that EGCG probably inhibits secretion by suppressing some metabolic mechanisms of T3SS.

http://ift.tt/2t3NZQL

The role of expectation in multisensory body representation: neural evidence

Abstract

Sensory events contribute to body ownership, the feeling that the body belongs to me. However, the encoding of sensory events is not only reactive, but also proactive in that our brain generates prediction about forthcoming stimuli. In previous studies we have shown that prediction of sensory events is a sufficient condition to induce the sense of body ownership. In this study we investigate the underlying neural mechanisms. Participants were seated with their right arm resting upon a table just below another smaller table. Hence, the real hand was hidden from the participant's view and a life-sized rubber model of a right hand was placed on the small table in front of them. Participants observed a wooden plank while approaching – without touching - the rubber hand. We measured the phenomenology of the illusion by means of questionnaire. Neural activity was recorded by means of near infrared spectroscopy (fNIRS). Results showed higher activation of multisensory parietal cortices in the rubber hand illusion induced by touch expectation. Furthermore, such activity was correlated with the subjective feeling of owning the rubber hand.

Our results enrich current models of body ownership suggesting that our multisensory brain regions generate prediction on what could be my body and what could not. This finding might have interesting implications in all those cases in which body representation is altered, anorexia, bulimia nervosa and obesity, among others.

This article is protected by copyright. All rights reserved.

http://ift.tt/2rZRxDJ

Within-class differences in cancer risk for sulfonylurea treatments in patients with type 2 diabetes (ZODIAC-55) – a study protocol

Abstract

Background

Patients with type 2 diabetes (T2D) are at increased risk for developing cancer. As approximately 8% of the world's population is living with T2D, even a slight increase in cancer risk could result in an enormous impact on the number of persons developing cancer. In addition, several glucose lowering drug classes for treating patients with T2D have been associated with a difference in risk of cancer overall, and especially for obesity related cancers. In what way and to what degree cancer risk is modified by the use of different sulfonylureas (SU) is unclear. The primary aim of this study will be to evaluate within-class SU differences in obesity related cancer risk. Secondary aims will be to investigate within-class SU differences in risk for all cancers combined and site-specific cancers separately (i.e. breast, colorectal, prostate, bladder and lung cancer) and to account for duration-response relationships between individual SU use and cancer risk.

Methods

Patients will be selected from a Dutch primary care cohort of patients with T2D linked with the Dutch Cancer Registration (ZODIAC-NCR). Within this cohort study annually collected clinical data (e.g. blood pressure, weight, HbA1c) and nationwide data on cancer incidence are available. Time-dependent cox proportional hazard analyses will be performed to evaluate SU cancer risk, adjusted for potential confounders.

Discussion

This study will be the first prospective cohort study investigating within-class SU differences in cancer risk and could contribute to improved decision making regarding the individual drugs within the class of SUs, and possibly improve quality of life and result in an increased cost-effectiveness of healthcare in patients with T2D.

Trial registration

Nederlands Trialregister (NTR6166), 6 Jan 2017.

http://ift.tt/2tX6bYV

Socioeconomic status is associated with symptom severity and sickness absence in people with infectious intestinal disease in the UK

The burden of infectious intestinal disease (IID) in the UK is substantial. Negative consequences including sickness absence are common, but little is known about the social patterning of these outcomes, or th...

http://ift.tt/2sZyhpb

Poorer outcomes among cancer patients diagnosed with Clostridium difficile infections in United States community hospitals

Cancer predisposes patients to Clostridium difficile infection (CDI) due to health care exposures and medications that disrupt the gut microbiota or reduce immune response. Despite this association, the national ...

http://ift.tt/2tXd24U

Erratum to: Trends in antimicrobial resistance and empiric antibiotic therapy of bloodstream infections at a general hospital in mid-Norway: a prospective observational study

http://ift.tt/2sZjX04

Comparing self- and provider-collected swabbing for HPV DNA testing in female-to-male transgender adult patients: a mixed-methods biobehavioral study protocol

Cervical cancer, nearly all cases of which are caused by one of several high-risk strains of the human papillomavirus (hr-HPV), leads to significant morbidity and mortality in individuals with a cervix. Trans ...

http://ift.tt/2tXcZGg

Microbiota-dependent metabolite and cardiovascular disease marker trimethylamine-N-oxide (TMAO) is associated with monocyte activation but not platelet function in untreated HIV infection

HIV infection is associated with increased risk of cardiovascular disease beyond that explained by traditional risk factors. Altered gut microbiota, microbial translocation, and immune activation have been pro...

http://ift.tt/2sZmrvk

Woman awarded for saving landlord's life with CPR

Ashley Neece was doing yard work with Valerie Pettit when she heard the lawn mower stop abruptly

http://ift.tt/2s3JEbS

Interictal oscillations and focal epileptic disorders

Abstract

Neuronal network oscillations represent a main feature of the brain activity recorded in the EEG under normal and pathological conditions such as epilepsy. Specific oscillations occur between seizures in patients and in animal models of focal epilepsy, and thus they are termed interictal. According to their shape and intrinsic signal frequency, interictal oscillations are classified as spikes and high frequency oscillations (HFOs). Interictal spikes are recorded in the "wideband" EEG signal and consist of large-amplitude events that usually last less than 1 s; HFOs, in contrast, are extracted by amplifying the appropriately filtered EEG signal, and are usually categorized as ripples (80-200 Hz) and fast ripples (250-500 Hz). Interictal spikes and HFOs are used in clinical practice to localize the seizure onset zone in focal epileptic disorders, which is fundamental for performing successful surgical interventions in epileptic patients not responding to antiepileptic drug therapy. Both types of interictal oscillations have been widely studied in animal models of focal epilepsy to identify the mechanisms underlying their generation as well as to establish their role in ictogenesis and epileptogenesis. In this review, we will address the cellular mechanisms underlying the generation of interictal spikes and HFOs in animal models of epileptiform synchronization and of focal epilepsy. Moreover, we will highlight in vitro and in vivo evidence indicating that these interictal oscillations mirror specific, dynamic changes in neuronal network excitability causing seizure generation (i.e., ictogenesis) and leading to a chronic epileptic condition (i.e., epileptogenesis).

This article is protected by copyright. All rights reserved.

http://ift.tt/2sKb9ZK

A genetic epidemiology study of Congenital Adrenal Hyperplasia in Italy

Abstract

Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (21OHD-CAH) is an autosomal recessive disorder affecting steroidogenesis, due to mutations in CYP21A2 (6p21.3). 21OHD-CAH neonatal screening is based on 17-hydroxyprogesterone (17OHP) serum levels, showing high type I error rate and low sensitivity to mild CAH forms.

Here, we used an epidemiological approach, which estimates the allelic frequency (q) of an autosomal recessive disorder using the proportion of homozygous patients, the mutational spectrum and the inbreeding coefficient in a sample of affected individuals. We applied this approach to two independent Italian cohorts of patients with both clinical and molecular diagnosis of 21OHD-CAH from mainland Italy (N = 240) and Sardinia (N = 53). We inferred q estimates of 2.87% and 1.83%, corresponding to a prevalence of 1/1,214 and 1/2,986, respectively. CYP21A2 mutational spectra were quite discrepant between the two cohorts, with V281L representing 74% of all the mutations detected in Sardinia vs 37% in mainland Italy.

These findings provide an updated fine-grained picture of 21OHD-CAH genetic epidemiology in Italy and suggest the need for a screening approach suitable to the detection of the largest number of clinically significant forms of CAH.

Graphical Abstract

http://ift.tt/2tWNBAa

Effectiveness and safety of moxibustion treatment for non-specific lower back pain: protocol for a systematic review

Introduction

Many patients experience acute lower back pain that becomes chronic pain. The proportion of patients using complementary and alternative medicine to treat lower back is increasing. Even though several moxibustion clinical trials for lower back pain have been conducted, the effectiveness and safety of moxibustion intervention is controversial. The purpose of this study protocol for a systematic review is to evaluate the effectiveness and safety of moxibustion treatment for non-specific lower back pain patients.

Methods and analysis

We will conduct an electronic search of several databases from their inception to May 2017, including Embase, PubMed, Cochrane Central Register of Controlled Trial, Allied and Complementary Medicine Database, Wanfang Database, Chongqing VIP Chinese Science and Technology Periodical Database, China National Knowledge Infrastructure Database, Korean Medical Database, Korean Studies Information Service System, National Discovery for Science Leaders, Oriental Medicine Advanced Searching Integrated System, the Korea Institute of Science and Technology, and KoreaMed. Randomised controlled trials investigating any type of moxibustion treatment will be included. The primary outcome will be pain intensity and functional status/disability due to lower back pain. The secondary outcome will be a global measurement of recovery or improvement, work-related outcomes, radiographic improvement of structure, quality of life, and adverse events (presence or absence). Risk ratio or mean differences with a 95% confidence interval will be used to show the effect of moxibustion therapy when it is possible to conduct a meta-analysis.

Ethics and dissemination

This review will be published in a peer-reviewed journal and will be presented at an international academic conference for dissemination. Our results will provide current evidence of the effectiveness and safety of moxibustion treatment in non-specific lower back pain patients, and thus will be beneficial to patients, practitioners, and policymakers.

Trial registration number

CRD42016047468 in PROSPERO 2016

http://ift.tt/2sy6kEh

The relationship between bicycle commuting and perceived stress: a cross-sectional study

Introduction

Active commuting — walking and bicycling for travel to and/or from work or educational addresses — may facilitate daily, routine physical activity. Several studies have investigated the relationship between active commuting and commuting stress; however, there are no studies examining the relationship between solely bicycle commuting and perceived stress, or studies that account for environmental determinants of bicycle commuting and stress. The current study evaluated the relationship between bicycle commuting, among working or studying adults in a dense urban setting, and perceived stress.

Methods

A cross-sectional study was performed with 788 adults who regularly travelled to work or study locations (excluding those who only commuted on foot) in Barcelona, Spain. Participants responded to a comprehensive telephone survey concerning their travel behaviour from June 2011 through to May 2012. Participants were categorised as either bicycle commuters or non-bicycle commuters, and (based on the Perceived Stress Scale, PSS-4) as either stressed or non-stressed. Multivariate Poisson regression with robust variance models of stress status based on exposures with bicycle commuting were estimated and adjusted for potential confounders.

Results

Bicycle commuters had significantly lower risk of being stressed than non-bicycle commuters (Relative Risk; RR (95% CI)=0.73 (0.60 to 0.89), p=0.001). Bicycle commuters who bicycled 4 days per week (RR (95% CI)=0.42 (0.24 to 0.73), p=0.002) and those who bicycled 5 or more days per week (RR (95% CI)=0.57 (0.42 to 0.77), p<0.001) had lower risk of being stressed than those who bicycled less than 4 days. This relationship remained statistically significant after adjusting for individual and environmental confounders and when using different cut-offs of perceived stress.

Conclusions

Stress reduction may be an important consequence of routine bicycle use and should be considered by decision makers as another potential benefit of its promotion.

http://ift.tt/2s39Gvy

Efficacy of adding a physiotherapy rehabilitation programme to arthroscopic management of femoroacetabular impingement syndrome: a randomised controlled trial (FAIR)

Objectives

Although several rehabilitation programmes following hip arthroscopy for femoracetabular impingement (FAI) syndrome have been described, there are no clinical trials evaluating whether formal physiotherapy-prescribed rehabilitation improves recovery compared with self-directed rehabilitation. The objective of this study was to evaluate the efficacy of adding a physiotherapist-prescribed rehabilitation programme to arthroscopic surgery for FAI syndrome.

Design

Randomised controlled trial.

Methods

People aged ≥16 years with FAI syndrome scheduled for hip arthroscopy were recruited and randomly allocated to physiotherapy (PT) or control. The PT group received seven PT sessions (one preoperative and six postoperative) incorporating education, manual therapy and a progressive rehabilitation programme of home, aquatic and gym exercises while the control group did not undertake PT rehabilitation. Measurements were taken at baseline (2 weeks presurgery) and 14 and 24 weeks postsurgery. The primary outcomes were the International Hip Outcome Tool (iHOT-33) and the sport subscale of the Hip Outcome Score (HOS) at week 14.

Results

Due to slower than expected recruitment and funding constraints, recruitment was ceased after 23 months. Thirty participants (14 PT and 16 control) were randomised and 28 (14 PT and 14 control; 93%) and 22 (11 PT and 11 control; 73%) completed week 14 and 24 measurements, respectively. For the 14-week primary outcomes, the PT group showed significantly greater improvements on the iHOT-33 (mean difference 14.2 units; 95% CI 1.2 to 27.2) and sport subscale of the HOS (13.8 units; 95% CI 0.3 to 27.3). There were no significant between-group differences at week 24.

Conclusions

An individual PT treatment and rehabilitation programme may augment improvements in patient-reported outcomes following arthroscopy for FAI syndrome. However, given the small sample size, larger trials are needed to validate the findings.

Trial registration number

Trial registered with the Australian New Zealand Clinical Trials Registry :ACTRN12613000282785, Results.

http://ift.tt/2syDEez

Variation in the prevalence of urinary catheters: a profile of National Health Service patients in England

Introduction

Harm from catheter-associated urinary tract infections is a common, potentially avoidable, healthcare complication. Variation in catheter prevalence may exist and provide opportunity for reducing harm, yet to date is poorly understood. This study aimed to determine variation in the prevalence of urinary catheters between patient groups, settings, specialities and over time.

Methods

A prospective study (July 2012 to April 2016) of National Health Service (NHS) patients surveyed by healthcare professionals, following a standardised protocol to determine the presence of a urinary catheter and duration of use, on 1 day per month using the NHS Safety Thermometer.

Results

1314 organisations (253 NHS trusts) and 9 266 284 patients were included. Overall, 12.9% of patients were catheterised, but utilisation varied. There was higher utilisation of catheters in males (15.7% vs 10.7% p<0.001) and younger people (18–70 year 14.0% vs >70 year 12.8% p<0.001), utilisation was highest in hospital settings (18.6% p<0.001), particularly in critical care (76.6% p<0.001). Most catheters had been in situ <28 days (72.9% p<0.001). No clinically significant changes were seen over time in any setting or specialty.

Conclusion

Catheter prevalence in patients receiving NHS-funded care varies according to gender, age, setting and specialty, being most prevalent in males, younger people, hospitals and critical care. Utilisation has changed only marginally over 46 months, and further guidance is indicated to provide clarity for clinicians on the insertion and removal of catheters to supplement the existing guidance on care.

http://ift.tt/2s3lTAw

The perspective of European researchers of national occupational safety and health institutes for contributing to a European research agenda: a modified Delphi study

Objectives

This study, developed within the frame of the Partnership for European Research on Occupational Safety and Health joint research activities and based on the frame designed by the 2013 European Agency for Safety and Health at Work (EU-OSHA) study, is the first example of using the points of view of European occupational safety and health (OSH) researchers.

The objective is to identify priorities for OSH research that may contribute to the achievement of present and future sustainable growth objectives set by the European strategies.

Methods

The study was carried out using a modified Delphi method with a two-round survey. Each round involved a panel of about 110 researchers representing the network member institutes was selected according to specific criteria, including the ownership of research expertise in at least one of the four macroareas identified by the reference report developed by EU-OSHA in 2013.

Results

The study identified some innovative research topics (for example, 'Emerging technological devices' and 'OSH consequences of markets integration') and research priorities (ie, crowdsourcing, e-work, zero-hours contracts) that are not reflected in previous studies of this nature.

The absence of any reference to violence and harassment at work among the researchers' proposals is a major difference from previous similar studies, while topics related to gender issues and electromagnetic fields show a lower importance.

Conclusions

The innovative design of a research priorities identification process, which takes advantage of a large, representative and qualified panel of European researchers allowed the definition of a number of research priorities able to support the inclusion of innovative OSH research issues in the scope of the next European research agenda.

http://ift.tt/2syem01

Effect of two additional interventions, test and reflection, added to standard cardiopulmonary resuscitation training on seventh grade students practical skills and willingness to act: a cluster randomised trial

Objectives

The aim of this research is to investigate if two additional interventions, test and reflection, after standard cardiopulmonary resuscitation (CPR) training facilitate learning by comparing 13-year-old students' practical skills and willingness to act.

Settings

Seventh grade students in council schools of two municipalities in south-east Sweden.

Design

School classes were randomised to CPR training only (O), CPR training with a practical test including feedback (T) or CPR training with reflection and a practical test including feedback (RT). Measures of practical skills and willingness to act in a potential life-threatening situation were studied directly after training and at 6 months using a digital reporting system and a survey. A modified Cardiff test was used to register the practical skills, where scores in each of 12 items resulted in a total score of 12–48 points. The study was conducted in accordance with current European Resuscitation Council guidelines during December 2013 to October 2014.

Participants

29 classes for a total of 587 seventh grade students were included in the study.

Primary and secondary outcome measures

The total score of the modified Cardiff test at 6 months was the primary outcome. Secondary outcomes were the total score directly after training, the 12 individual items of the modified Cardiff test and willingness to act.

Results

At 6 months, the T and O groups scored 32 (3.9) and 30 (4.0) points, respectively (p<0.001), while the RT group scored 32 (4.2) points (not significant when compared with T). There were no significant differences in willingness to act between the groups after 6 months.

Conclusions

A practical test including feedback directly after training improved the students' acquisition of practical CPR skills. Reflection did not increase further CPR skills. At 6-month follow-up, no intervention effect was found regarding willingness to make a life-saving effort.

http://ift.tt/2s3dFbJ

Cognitive screening and behavioural observation of functional ability in patients with multiple episode schizophrenia: an exploratory study

Objectives

To evaluate the usability of a neuropsychological screening instrument and two observation scales of everyday behaviour to describe cognitive and functional capacity of patients with multiepisode schizophrenia and considerable care needs, who frequently refuse to participate in cognitive testing or performance-based functional measurement.

Setting

One psychiatric unit specialised in severe mental illness at the Sahlgrenska University Hospital, Gothenburg, Sweden.

Participants

Patients were included consecutively from date of admission to the unit. Inclusion criteria: age 18–65 years, International Classification of Diseases 10 diagnoses F20.0–F20.9 (schizophrenia) or F25.0-F25.9 (schizoaffective disorder) since at least 5 years. Exclusion criteria: acute serious psychotic episodes or physical illness, alcohol or drug abuse during the year before the study, diagnosed cerebral disorder at admission to the unit, and insufficient ability to speak Swedish. 64 patients filled the criteria and 19 accepted participation: 14 males, 5 females, median age 56 years.

Outcome measures

Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) scores, measured by a psychologist; Frontal Systems Behaviour Scale (FrSBe) Family Version and Functional Independence Measure (FIM) V.4.0 scores, measured by nursing staff. Non-parametric statistics were consistently applied to process the data.

Results

Failure analysis showed differences regarding gender and subdiagnoses between participants and non-participants. All participants had BNIS scores indicating cognitive dysfunction. FrSBe group medians showed apathy and executive problems, indicating possible frontal lobe disturbance. FIM showed dependency on others for linguistic and social communication, everyday problem solving, and remembering persons and daily routines. Correlations between FrSBe and FIM (p≤0.01) suggested executive dysfunction being crucial to explain difficulties in performing activities of daily functioning.

Conclusions

Indications of considerable cognitive and functional difficulties found among the participants suggestedthat the instruments are clinically applicable for tentative assessment of cognitive and functional ability among patients with multiepisode schizophrenia and considerable care needs.

http://ift.tt/2sy9qZ8

Assessing the impact of colonoscopy complications on use of colonoscopy among primary care physicians and other connected physicians: an observational study of older Americans

Objectives

Psychological biases can distort treatment decision-making. The availability heuristic is one such bias, wherein events that are recent, vivid or easily imagined are readily 'available' to memory and are therefore judged more likely to occur than expected based on epidemiological data. We assessed if the occurrence of a serious colonoscopy complication for a primary care physician's patient influenced colonoscopy rates for the physician's other patients.

Design

Longitudinal study with time-varying exposure variables.

Setting/participants

Individuals living in 51 hospital referral regions across the USA identified based on enrolment in fee-for-service Medicare during 2005–2010. We assigned patients to a primary care physician based on office visits during the prior 2 years.

Exposures

For each physician in each month, we calculated the proportion of patients assigned to them who had a colonoscopy. We identified two serious complications of which the primary care provider would very likely be aware: gastrointestinal bleed or perforation leading to hospitalisation or death within 14 days of colonoscopy.

Main outcome measures

We employed Poisson regression models including physician fixed effects to assess the change in number of colonoscopies in the four quarters following an adverse colonoscopy event.

Results

We identified 5 360 191 patients assigned to 30 704 physicians. 4864 physicians (16%) had at least one patient with an adverse event. The estimated change in the quarterly number of colonoscopies among physicians' patients was significantly lower in quarter 2 following an adverse colonoscopy event (change=–2.1% (95% CI –3.4 to –0.8%)), before returning to the rate expected in the absence of an adverse event.

Conclusions

Having a patient experience a serious adverse colonoscopy event was associated with a small and temporary decline in colonoscopy rates among a physician's other patients. This finding provides empirical evidence for the influence of notable adverse events on care, possibly due to the availability heuristic.

http://ift.tt/2s3Hfhc

The predictive value of serial changes in diaphragm function during the spontaneous breathing trial for weaning outcome: a study protocol

Introduction

There is a variety of tools being used in clinical practice for the prediction of weaning success from mechanical ventilation. However, their diagnostic performances are less than satisfactory. The purpose of this study is to investigate the value of serial changes in diaphragm function measured by ultrasound during the spontaneous breathing trial (SBT) as a weaning predictor.

Methods and analysis

This is a prospective observational study conducted in a 10-bed medical emergency intensive care unit (EICU) in a university-affiliated hospital. The study will be performed from November 2016 to December 2017. All patients in the EICU who are expected to have mechanical ventilation for more than 48 hours through endotracheal tube are potentially eligible for this study. Patients will be included if they fulfil the criteria for SBT. All enrolled patients will be ventilated with an Evita-4 by using volume assist control mode prior to SBT. Positive end-expiratory pressure (PEEP) will be set to 5 cmH₂O and fractional inspired oxygen (FiO₂) will be set to a value below 0.5 that guarantees oxygen saturation by pulse oximetry (SpO₂) greater than 90%. Enrolled patients will undergo SBT for 2 hours in semirecumbent position. During the SBT, the patients will breathe through the ventilator circuit by using flow triggering (2 L/min) with automatic tube compensation of 100% and 5 cmH₂O PEEP. The FiO₂ will be set to the same value as used before SBT. If the patients fail to tolerate the SBT, the trial will be discontinued immediately and the ventilation mode will be switched to that used before the trial. Patients who pass the 2-hour SBT will be extubated. Right diaphragm excursion and bilateral diaphragm thickening fraction will be measured by ultrasonography during spontaneous breathing. Images will be obtained immediately prior to the SBT, and at 5, 30, 60, 90 and 120 min after the initiation of SBT. Rapid shallow breathing index will be simultaneously calculated at the bedside by a respiratory nurse.

Ethics and dissemination

The study protocol is approved by the ethics committee of Sir Run Run Shaw Hospital, an affiliate of Zhejiang University, Medical College. The results will be published in a peer-reviewed journal and shared with the worldwide medical community.

Trial registration number

ISRCTN42917473; Pre-results.

http://ift.tt/2syxf33

A combined randomised and observational study of surgery for fractures in the distal radius in the elderly (CROSSFIRE)--a study protocol

Fractures of the distal radius are common and occur in all age groups. The incidence is high in older populations due to osteoporosis and increased falls risk. Considerable practice variation exists in the management of distal radius fractures in older patients ranging from closed reduction with cast immobilisation to open reduction with plate fixation. Plating is currently the most common surgical treatment. While there is evidence showing no significant advantage for some forms of surgical fixation over conservative treatment, and no difference between different surgical techniques, there is a lack of evidence comparing two of the most common treatments used: closed reduction and casting versus plating. Surgical management involves significant costs and risks compared with conservative management. High-level evidence is required to address practice variation, justify costs and to provide the best clinical outcomes for patients.

Methods and analysis

This pragmatic, multicentre randomised comparative effectiveness trial aims to determine whether plating leads to better pain and function and is more cost-effective than closed reduction and casting of displaced distal radius fractures in adults aged 60 years and older. The trial will compare the two techniques but will also follow consenting patients who are unwilling to be randomised in a separate, observational cohort. Inclusion of non-randomised patients addresses selection bias, provides practice and outcome insights about standard care, and improves the generalisability of the results from the randomised trial.

Ethics and dissemination

CROSSFIRE(Combined Randomised and Observational Study of Surgery for Fractures In the distal Radius in the Elderly) was reviewed and approved by The Hunter New England HREC (HNEHREC Reference No: 16/02/17/3.04). The results of the trial will be published in a peer-reviewed journal and will be disseminated via various forms of media. Results will be incorporated in clinical recommendations and practice guidelines produced by professional bodies.

Registration

CROSSFIRE has been registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR: ACTRN12616000969460).

http://ift.tt/2s3ps9L

Role, structure and effects of medical tourism in Africa: a systematic scoping review protocol

Introduction

Some patients travel out of, while others come into Africa for medical care through a growing global phenomenon referred to as medical tourism (MT): the travel in search of medical care that is either unavailable, unaffordable or proscribed at home healthcare systems. While some castigate MT as promoting healthcare inequity, others endorse it as a revenue generator, promising local healthcare system strengthening. Currently, however, the understanding of this component of healthcare in Africa is inadequate. This study seeks to determine the level of knowledge on the role, structure and effect of MT in Africa as it relates to healthcare systems in the region.

Methods

Conduct a systematic scoping review to outline the role, structure and effect of MT in Africa. Databases: Academic Search Complete, Business Source Complete. Studies mapped in two stages: (1) mapping the studies based on the relevance of their titles and subject descriptors; (2) applying further inclusion criteria on studies from stage 1. Two reviewers will independently assess study quality and abstract data. Both quantitative and qualitative data analysis will be performed, using STATA V.13 and NVIVO, respectively.

Ethics and dissemination

The study results will be disseminated by publication in peer-reviewed journals and findings presented at academic and industry conferences related to MT, public health, health systems strengthening and tourism.

Discussion

MT spurs cutting-edge medical technologies, techniques and best practices in healthcare delivery. The two-tier healthcare landscape in Africa, however, presents an exceptionally unique context in which to situate this study. Much has been written about MT globally, but not much is known about the phenomenon in Africa; hence the appropriateness of this scientific assessment of MT in the region. By elucidating the role, structure and effect of this phenomenon, this study hopes to contribute to health systems strengthening in Africa.

PROSPERO registration number

CRD42016039745.

http://ift.tt/2syekVX

Officials: EMTs, firefighters endangered by erratic 911 system

Authorities said the malfunctions in the system deprives responders of recent emergency information

http://ift.tt/2t2pRy9

Intra-articular lipoma of the hip

Intra-articular lipoma of the hip is a rare entity, with only two reports published in the English-language literature. We present a case of successful arthroscopic resection of an intra-articular peripheral compartment lipoma in a 69-year-old woman with a coincident labral tear. This woman presented with left hip pain that developed gradually over 2 years and increased over 2 months. MRI showed a fat-intense mass in the anterior aspect of the hip joint, convincing for intra-articular lipoma. Physical examination in the operating room reproduced decreased range of motion and evidence of impingement but with a soft endpoint. Arthroscopy revealed an anterior intrasubstance labral tear, which was debrided. The mass was excised and confirmed as true lipoma on histology. The soft endpoint on examination illustrates that a large lipoma of the hip joint can cause clinical symptoms of impingement in the absence of bony abnormality or trauma.

http://ift.tt/2tBNI4X

The cause of the stroke: a diagnostic uncertainty

A 39-year-old man with a history of sickle cell disease (SCD) presented with left leg weakness. He had a normal CT head and CT angiogram, but MRI head showed multiple acute bilateral cortical infarcts including in the right precentral gyrus. The MRI findings were more in keeping with an embolic source rather than stroke related to SCD, although it could not be ruled out. He also had an echocardiogram which revealed a patent foramen ovale. He was treated with antiplatelet therapy and also had red blood cell exchange transfusion. His symptoms improved significantly and he was discharged with follow-up as an outpatient and a cardiology review.

http://ift.tt/2t2se47

An unusual case of abdominal pains

Description

A 55-year-old African American man presented to the emergency room with 3 days of new-onset right-sided flank and abdominal pains. His abdominal pains were dull in nature, constant, moderate in severity (approximately 6 out of 10) and radiated to his back and right flank regions. There were no aggravating factors but the patient reported temporary relief with over-the-counter acetaminophen. The pains were associated with mild nausea and vomiting but he denied diarrhoea, constipation, weight loss, fevers or other associated symptoms. His only known medical history was hypertension, controlled with lisinopril. Surgical, social and family history were unremarkable. Other than abdominal pains, a complete review of systems was negative. His blood pressure was 117/78 mm Hg and his pulse was 82 bpm. His physical examination revealed right flank and right lower quadrant abdominal pain without rebound or guarding.

He underwent an abdominal CT scan which showed a 5.2 cmx4.2 cm hypodensed solid right...

http://ift.tt/2tBO2kf