Medicine by Alexandros G.Sfakianakis: 10/24/18

Τετάρτη 24 Οκτωβρίου 2018

Evaluation of the venous drainage pattern of the splenic flexure by preoperative three‐dimensional computed tomography

Asian Journal of Endoscopic Surgery, EarlyView.

https://ift.tt/2Ari3Zu

Prostate cancer diagnostic pathway: Is a one-stop cognitive MRI targeted biopsy service a realistic goal in everyday practice? A pilot cohort in a tertiary referral centre in the UK

Objectives

To evaluate the feasibility of a novel multiparametric MRI (mpMRI) and cognitive fusion transperineal targeted biopsy (MRTB) led prostate cancer (PCa) diagnostic service with regard to cancer detection and reducing time to diagnosis and treatment.

Design

Consecutive men being investigated for possible PCa under the UK 2-week wait guidelines.

Setting

Tertiary referral centre for PCa in the UK.

Participants

Men referred with a raised prostate-specific antigen (PSA) or abnormal digital rectal examination between February 2015 and March 2016 under the UK 2-week rule guideline.

Interventions

An mpMRI was performed prior to patients attending clinic, on the same day. If required, MRTB was offered. Results were available within 48 hours and discussed at a specialist multidisciplinary team meeting. Patients returned for counselling within 7 days

Primary and secondary outcome measures

Outcome measures in this regard included the time to diagnosis and treatment of patients referred with a suspicion of PCa. Quality control outcome measures included clinically significant and total cancer detection rates.

Results

112 men were referred to the service. 111 (99.1%) underwent mpMRI. Median PSA was 9.4 ng/mL (IQR 5.6–21.0). 87 patients had a target on mpMRI with 25 scoring Likert 3/5 for likelihood of disease, 26 4/5 and 36 5/5.

57 (51%) patients received a local anaesthetic, Magnetic resonance imaging targeted biopsy (MRTB). Cancer was detected in 45 (79%). 43 (96%) had University College London definition 2 disease or greater. The times to diagnosis and treatment were a median of 8 and 20 days, respectively.

Conclusions

This approach greatly reduces the time to diagnosis and treatment. Detection rates of significant cancer are high. Similar services may be valuable to patients with a potential diagnosis of PCa.

https://ift.tt/2Q1w6tS

Percutaneous coronary intervention in patients with acute coronary syndrome in Chinese Military Hospitals, 2011-2014: a retrospective observational study of a national registry

Objectives

Interventional treatment of patients with acute coronary syndrome (ACS) is surging dramatically in China in recent years, whereas nationwide assessments of the quality of percutaneous coronary intervention (PCI) procedural performance and outcomes are scarce. We aimed to provide an updated and real-world overview of the performance of PCI in patients with ACS since 2011 in China after the China PEACE study from 2001 to 2011.

Methods

In this cross-sectional study, data were extracted from the National Registry of Cardiovascular Intervention in Military Hospitals database to create a national sample of 144 659 patients with ACS undergoing PCI at 117 military hospitals in all regions of China from calendar years 2011–2014. Patient characteristics, procedural performance, PCI outcomes and adverse events and temporal changes were analysed.

Results

During 2011–2014, patients with ACS undergoing PCI increased dramatically. Small numbers of high-volume hospitals performed the majority of PCI procedures. However, only half of these patients were adequately covered and proportions for the use of assisted devices and novel medications were relatively small. Radial artery access was still increasing with time. Primary PCIs were performed on 45.4% ST-segment elevation myocardial infarction patients with PCI procedures. 3.8% lesion vessels involve left main artery. Implanted stents, the overall complications and in-hospital mortality were decreasing remarkably.

Conclusions

In Chinese military hospitals, interventional resources were limited with great regional disparities, there are still gaps to be filled to better serve patients with ACS. Our findings can serve as an indispensable supplement to a more comprehensive understanding of the practice of contemporary cardiac intervention in China.

https://ift.tt/2ArlQ8V

Evaluating methodological quality of Prognostic models Including Patient-reported HeAlth outcomes iN oncologY (EPIPHANY): a systematic review protocol

Introduction

While there is mounting evidence of the independent prognostic value of patient-reported outcomes (PROs) for overall survival (OS) in patients with cancer, it is known that the conduct of these studies may hold a number of methodological challenges. The aim of this systematic review is to evaluate the quality of published studies in this research area, in order to identify methodological and statistical issues deserving special attention and to also possibly provide evidence-based recommendations.

Methods and analysis

An electronic search strategy will be performed in PubMed to identify studies developing or validating a prognostic model which includes PROs as predictors. Two reviewers will independently be involved in data collection using a predefined and standardised data extraction form including information related to study characteristics, PROs measures used and multivariable prognostic models. Studies selection will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with data extraction form using fields from the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist for multivariable models. Methodological quality assessment will also be performed and will be based on prespecified domains of the CHARMS checklist. As a substantial heterogeneity of included studies is expected, a narrative evidence synthesis will also be provided.

Ethics and dissemination

Given that this systematic review will use only published data, ethical permissions will not be required. Findings from this review will be published in peer-reviewed scientific journals and presented at major international conferences. We anticipate that this review will contribute to identify key areas of improvement for conducting and reporting prognostic factor analyses with PROs in oncology and will lay the groundwork for developing future evidence-based recommendations in this area of research.

Prospero registration number

CRD42018099160.

https://ift.tt/2Q1x49u

Assessing the operational feasibility and acceptability of an inhalable formulation of oxytocin for improving community-based prevention of postpartum haemorrhage in Myanmar: a qualitative inquiry

Objective

This study assessed the potential operational feasibility and acceptability of a heat-stable, inhaled oxytocin (IOT) product for community-based prevention of postpartum haemorrhage in Myanmar.

Methods

A qualitative inquiry was conducted between June 2015 and February 2016 through focus group discussions and in-depth interviews. Research was conducted in South Dagon township (urban setting) and in Ngape and Thanlyin townships (rural settings) in Myanmar. Eleven focus group discussions and 16 in-depth interviews were conducted with mothers, healthcare providers and other key informants. All audio recordings were transcribed verbatim in Myanmar language and were translated into English. Thematic content analysis was done using NVivo software.

Results

Future introduction of an IOT product for community-based services was found to be acceptable among mothers and healthcare providers and would be feasible for use by lower cadres of healthcare providers, even in remote settings. Responses from healthcare providers and community members highlighted that midwives and volunteer auxiliary midwives would be key advocates for promoting community acceptance of the product. Healthcare providers perceived the ease of use and lack of dependence on cold storage as the main enablers for IOT compared with the current gold standard oxytocin injection. A single-use disposable device with clear pictorial instructions and a price that would be affordable by the poorest communities was suggested. Appropriate training was also said to be essential for the future induction of the product into community settings.

Conclusion

In Myanmar, where home births are common, access to cold storage and skilled personnel who are able to deliver injectable oxytocin is limited. Among community members and healthcare providers, IOT was perceived to be an acceptable and feasible intervention for use by lower cadres of healthcare workers, and thus may be an alternative solution for the prevention of postpartum haemorrhage in community-based settings in the future.

https://ift.tt/2ApIYVl

Protocol for a randomised controlled trial to study cryoprevention of chemotherapy-induced oral mucositis after autologous stem cell transplantation

Introduction

A majority of patients who receive myeloablative therapy prior to hematopoetic stem cell transplantation develop oral mucositis (OM). This adverse cytotoxic effect manifests as oral mucosal erythema and ulcerations and frequently necessitates high doses of morphine for pain alleviation. OM may also interfere with food intake and result in parenteral nutrition, weight loss and impaired quality of life. To date, there have been a few studies of evidence-based interventions for prevention of OM. Cooling the oral mucosa using ice chips in conjunction with chemotherapy is known to reduce the severity of OM although clinical application is still limited due to several disadvantages. The primary endpoint of this study is therefore to evaluate the efficacy of an innovative intraoral cooling device (Cooral) compared with ice cooling in reducing the degree of OM, in patients with myeloma or lymphoma.

Method and analysis

A total of 180 patients from four different university hospitals in Sweden will be randomised to ice or Cooral in a proportion of 1:1. The degree of OM will be assessed at eight intraoral locations, in accordance with the Oral Mucositis Assessment Scale and WHO scale. Patients will be registered beginning at admission and will continue until discharge or until day +28. The primary variable is analysed in a multiple linear regression model. The significance level used is 5%.

Ethics and dissemination

The study protocol, questionnaire, diaries and letter of invitation to participants have been reviewed by the local ethical board in Göteborg. The trial results will be published in a peer-reviewed journal and disseminated to participants.

Trial registration number

NCT03203733; Pre-results.

Protocol version

Version 4, 2017-06-05

https://ift.tt/2PUQdu3

Depression, depressive symptoms and treatments in women who have recently given birth: UK cohort study

Objectives

To investigate how depression is recognised in the year after child birth and treatment given in clinical practice.

Design

Cohort study based on UK primary care electronic health records.

Setting

Primary care.

Participants

Women who have given live birth between 2000 and 2013.

Outcomes

Prevalence of postnatal depression, depression diagnoses, depressive symptoms, antidepressant and non-pharmacological treatment within a year after birth.

Results

Of 206 517 women, 23 623 (11%) had a record of depressive diagnosis or symptoms in the year after delivery and more than one in eight women received antidepressant treatment. Recording and treatment peaked 6–8 weeks after delivery. Initiation of selective serotonin reuptake inhibitors (SSRI) treatment has become earlier in the more recent years. Thus, the initiation rate of SSRI treatment per 100 pregnancies (95% CI) at 8 weeks were 2.6 (2.5 to 2.8) in 2000–2004, increasing to 3.0 (2.9 to 3.1) in 2005–2009 and 3.8 (3.6 to 3.9) in 2010–2013. The overall rate of initiation of SSRI within the year after delivery, however, has not changed noticeably. A third of the women had at least one record suggestive of depression at any time prior to delivery and of these one in four received SSRI treatment in the year after delivery.

Younger women were most likely to have records of depression and depressive symptoms. (Relative risk for postnatal depression: age 15–19: 1.92 (1.76 to 2.10), age 20–24: 1.49 (1.39 to 1.59) versus age 30–34). The risk of depression, postnatal depression and depressive symptoms increased with increasing social deprivation.

Conclusions

More than 1 in 10 women had electronic health records indicating depression diagnoses or depressive symptoms within a year after delivery and more than one in eight women received antidepressant treatment in this period. Women aged below 30 and from the most deprived areas were at highest risk of depression and most likely to receive antidepressant treatment.

https://ift.tt/2ApIU83

Self-rated health among migrants from the former Soviet Union in Germany: a cross-sectional study

Objectives

To assess the status and change in self-rated health among Aussiedler, ethnic German immigrants from the former Soviet Union, as a predictor for premature death 10 years after first assessment. Moreover, to identify subgroups which are particular at risk of anticipated severe health impairment.

Design

Cross-sectional questionnaire.

Setting

The study was conducted in the catchment area of Augsburg, a city in southern Bavaria, Germany, in 2011/2012 that has a large community of Aussiedler.

Participants

595 Aussiedler (231 male, 364 female, mean age 55 years) who in majority migrated to Germany between 1990 and 1999.

Outcome

Primary outcome: self-rated health (very good/good/not so good/bad) and its association with demographic, social and morbidity related variables.

Methods

Self-rated health was dichotomised as 'very good' and 'good' versus 'not so good' and 'bad'. Multivariable logistic models were created. Missing values with regard to pain were addressed by a second analysis.

Results

Although low response suggests a healthier sample, the findings are alarming. Altogether47% of the Aussiedler perceived their health as less than good, which is worse compared with the first assessment in 2000 (25% compared with 20% of the general public). Prevalence of high blood pressure was present in 52% of Aussiedler, 34.5% were obese, 40.7% suffered from frequent pain and 13.1% had diabetes mellitus. According to the multivariable models, individuals suffering from pain, limited mobility, diabetes mellitus and high blood pressure are particularly in jeopardy.

Conclusions

10 years after the first assessment of self-rated health among Aussiedler their situation deteriorated. Tailored risk factor counselling of general practitioners is highly recommended.

https://ift.tt/2PSFpfH

Equity and determinants of routine child immunisation programme among tribal and non-tribal populations in rural Tangail subdistrict, Bangladesh: a cohort study

Objectives

The study estimated valid vaccination coverage of under 5 children in a rural area under Tangail subdistrict and examined their sociodemographic correlates including ethnicity.

Setting

The study sites are three primary areas where tribal and non-tribal population resides together in a rural subdistrict of Bangladesh.

Participants

Routine vaccination information of a cohort of 2802 children, born between 1 January 2011 and 31 December 2012, were retrieved from the Expanded Program on Immunization (EPI) registers maintained by the health assistants. Collected data were entered in an Oracle-based computer program. Univariate, bivariate and multivariate analyses were performed in SPSS V.20 to explore coverage and differentials for full valid vaccination coverage in the study area.

Results

Valid vaccination coverage was 90.6% among tribal population and 87.3% among non-tribal population(p=0.25). Compared with females, males had higher valid vaccination coverage (89.2% vs 85.9%) and lower invalid (5.4% vs 6.9%) and no-coverage (5.3% vs 7.3%) (p=0.03). Households with mobile phones had higher valid coverage (90.9% vs 86.5%) and lower invalid (4.5% vs 6.7%) and no coverage (4.5% vs 6.9%) compared with those without mobile phones (p=0.01). Coverage of valid vaccination was higher among children of Oronkhola union than in children of the other two unions.

Conclusion

The study documented that valid vaccination coverage was high in this rural area, and there was no significant ethnic variation which was one of the strengths of the national EPI. However, there is significant variation by gender of the child, household ownership of mobile phones and geographical location of households.

https://ift.tt/2ApIOgH

Qualitative study to explore the views of general practice staff on the use of point-of-care C reactive protein testing for the management of lower respiratory tract infections in routine general practice in England

Objectives

To explore the knowledge, skills, attitudes and beliefs of general practice staff about C reactive protein (CRP) point-of-care tests (POCTs) in routine general practice and associated barriers and facilitators to implementing it to improve the management of acute cough.

Design

A qualitative methodology including interviews and focus groups using the Com-B framework to understand individuals' behaviour to implement CRP POCT in routine general practice. Data were analysed inductively and then aligned to the Com-B framework.

Setting

A service evaluation of CRP POCT over a 6-month period was previously conducted in randomly selected GP practices from a high prescribing National Health Service Clinicial Commissioning Groups in England. All 11 intervention practices (eight accepting CRPs; three declining CRPs) and the eight control practices, which were not offered CRP POCT, were also invited to interview. A further randomly selected practice not allocated to intervention or control was also invited to participate.

Participants

Seven of eight accepting CRP, one of three declining CRP and four of nine control practices consented to participate. 12 practices and 26 general practice staff participated; 11 interviews, 3 focus groups and 1 hand-written response.

Results

Participants reported that CRP POCT can increase diagnostic certainty for acute cough, inform appropriate management, manage patient expectations for antibiotics, support patient education and improve appropriate antibiotic prescribing. Reported barriers to implementing CRP POCT included: CRP cost, time, easy access to the POCT machine and effects on clinical workflow. Participants with greater CRP use usually had a dedicated staff member with the machine located in their consultation room.

Conclusions

CRP POCT can help general practice staff improve patient care and education if incorporated into routine care, but this will need enthusiasts with dedicated POCT instruments or smaller, cheaper, more portable machines. In addition, funding will be needed to support test costs and staff time.

https://ift.tt/2Q1wFUw

Caesarean section in Palestine using the Robson Ten Group Classification System: a population-based birth cohort study

Objective

To analyse the current situation of caesarean section in Palestine using the Robson Ten Group Classification System (TGCS).

Design

A population-based birth cohort study.

Setting

Obstetrical departments in three governmental hospitals in Gaza.

Participants

All women (18 908) who gave birth between 1 January 2016 and 30 April 2017.

Methods

The contributions of each group to the study population and to the overall rate of caesarean section were calculated, as well as the rate of caesarean section in each TGCS group. Differences in proportions between study hospitals were assessed by ² test.

Main outcome measures

The main outcome was the contributions of each group to the overall caesarean section rate.

Results

The overall rate of caesarean section was 22.9% (4337 of 18 908), ranging from 20.6% in hospital 1 to 24.6% in hospital 3. The largest contributors to the overall caesarean section rate were multiparous women with single cephalic full-term pregnancy who had undergone at least one caesarean section (group 5, 42.6%), women with multiple pregnancies (group 8, 11.6%) and those with single cephalic preterm labour (group 10, 8.1%). Statistically significant differences in caesarean section rates between the study hospitals were observed in group 1 (nulliparous women with single cephalic full-term pregnancy and spontaneous labour), group 4 (multiparous with single cephalic full-term pregnancy with induced labour or prelabour caesarean section), group 5 (multiparous with single cephalic full-term pregnancy with previous caesarean section) and in group 7 (multiparous with breech presentation).

Conclusion

Women in groups 5, 8 and 10 were the largest contributors to the overall caesarean section rate in the study hospitals. Efforts to reduce the differences in obstetrical care between hospitals need to be directed towards increasing the proportion of vaginal births after caesarean section and by reducing primary caesarean section in multiple pregnancies and preterm labour.

https://ift.tt/2ApIAGn

Is the alcohol industry doing well by 'doing good? Findings from a content analysis of the alcohol industrys actions to reduce harmful drinking

Objectives

The aims of this study were to: (1) describe alcohol industry corporate social responsibility (CSR) actions conducted across six global geographic regions; (2) identify the benefits accruing to the industry ('doing well'); and (3) estimate the public health impact of the actions ('doing good').

Setting

Actions from six global geographic regions.

Participants

A web-based compendium of 3551 industry actions, representing the efforts of the alcohol industry to reduce harmful alcohol use, was issued in 2012. The compendium consisted of short descriptions of each action, plus other information about the sponsorship, content and evaluation of the activities. Public health professionals (n=19) rated a sample (n=1046) of the actions using a reliable content rating procedure.

Outcome measures

WHO Global strategy target area, estimated population reach, risk of harm, advertising potential, policy impact potential and other aspects of the activity.

Results

The industry actions were conducted disproportionately in regions with high-income countries (Europe and North America), with lower proportions in Latin America, Africa and Asia. Only 27% conformed to recommended WHO target areas for global action to reduce the harmful use of alcohol. The overwhelming majority (96.8%) of industry actions lacked scientific support (p<0.01) and 11.0% had the potential for doing harm. The benefits accruing to the industry ('doing well') included brand marketing and the use of CSR to manage risk and achieve strategic goals.

Conclusion

Alcohol industry CSR activities are unlikely to reduce harmful alcohol use but they do provide commercial strategic advantage while at the same time appearing to have a public health purpose.

https://ift.tt/2AqvBV4

Binary Bias Distorts How We Integrate Information

When we evaluate and compare a range of data points – whether that data is related to health outcomes, head counts, or menu prices – we tend to neglect the relative strength of the evidence and treat it as simply binary, according to research published in Psychological Science, a journal of the Association for Psychological Science.

"People show a strong tendency to dichotomize data distributions and ignore differences in the degree to which instances differ from an explicit or inferred midpoint," says psychological scientist Matthew Fisher of Carnegie Mellon University, first author on the research. "This tendency is remarkably widespread across a diverse range information formats and content domains, and our research is the first to demonstrate this general tendency."

In a series of six studies, Fisher and coauthor Frank C. Keil of Yale University examined how people tend to reduce a continuous range of data points into just two categories.

"Especially in the Internet age, people have access to an overwhelming amount of information," says Fisher. "We have been interested in how people make sense of all the data at their fingertips."

Fisher and Keil hypothesized that people would implicitly create an "imbalance score," analyzing the difference in data points that fall on one side of a given boundary and those that fall on the other side. If people are evaluating data from different studies investigating the relationship between caffeine and health, for example, they would quickly categorize data as either showing an effect or not, regardless of the relative strength of the evidence.

In one online study, Fisher and Keil randomly assigned a total of 605 participants to consider a specific topic related to either scientific reports, eyewitness testimonies, social judgments, or consumer reviews. They saw a series of 17 claims about the relationship between two variables, such as taking a certain medication and experiencing feelings of hunger (e.g., "One group of scientists found that the new medication makes feeling hungry 2 times more likely," "One group of scientists found that the new medication makes feeling hungry 4 times less likely").

After viewing the claims, participants then summarized the evidence, choosing the rating that best captured their overall impression.

As hypothesized, the imbalance score – the number of strong and weak negative evidence claims subtracted from the number of strong and weak positive evidence claims – was associated with participants' summary judgments. Their summary judgments were also influenced by the first piece evidence they saw.

Further evidence for the impact of imbalance score on participants' estimates emerged in two additional online studies, in which people saw data presented in various forms, including vertical and horizontal bar charts, pie charts, verbal descriptions with or without percentages, and dot plots.

The binary bias even appeared in the context of real-world decision making: Participants seemed to collapse data into two categories whether they were evaluating menu prices or determining which factories had higher carbon dioxide output. In both of these domains, participants' judgments were influenced by the imbalance score implied by the data.

"We were surprised by the pervasiveness of the effect across contexts and content domains," says Fisher. "The binary bias influenced how people interpret sequences of information and a wide variety of graphical displays."

The fact that the bias is so pervasive suggests that it is not due to a specific feature of data visualization or statistical information but is instead a general cognitive illusion. Fisher and Keil suspect that this cognitive distortion may offer a cognitive shortcut that allows us to process large amounts of information relatively efficiently.

"Our work suggests the bias is a basic processing mechanism which is applied across many contexts, including health, financial and public-policy decisions," the researchers conclude.

All data and materials have been made publicly available via the Open Science Framework. The complete Open Practices Disclosure for this article is available online. This article has received the badges for Open Data and Open Materials.

https://ift.tt/2q7mRgF

Big Data in Head and Neck Cancer

Opinion statement

Head and neck cancers can be used as a paradigm for exploring "big data" applications in oncology. Computational strategies derived from big data science hold the promise of shedding new light on the molecular mechanisms driving head and neck cancer pathogenesis, identifying new prognostic and predictive factors, and discovering potential therapeutics against this highly complex disease. Big data strategies integrate robust data input, from radiomics, genomics, and clinical-epidemiological data to deeply describe head and neck cancer characteristics. Thus, big data may advance research generating new knowledge and improve head and neck cancer prognosis supporting clinical decision-making and development of treatment recommendations.

https://ift.tt/2D5VU5F

Anaplastic Glioma: Treatment Approaches in the Era of Molecular Diagnostics

Opinion statement

The treatment paradigm for anaplastic glioma has shifted, owing to new diagnostic criteria and new phase III clinical trial evidence. In 2016, the WHO classification of brain tumors including diffuse gliomas was redefined to include molecular criteria, often supplanting the morphological appearance of the tumor cells. This was necessary as prognosis is more closely associated with molecular diagnosis than with morphology and grade. Recently, the benefit of adjuvant chemotherapy in addition to radiotherapy has been demonstrated in both anaplastic oligodendroglioma and anaplastic astrocytoma, as well as lower grade gliomas with the most marked benefit evident in IDH-mutated (astrocytoma) and 1p/19q co-deleted (oligodendroglial) tumors. The defining principle of recent breakthroughs has been the benefit of combinatorial therapy (chemo-radiation) as opposed to treatment in series or treatment of either modality after a period of observation upon evidence of progression.

https://ift.tt/2EIJGBp

Allogeneic Hematopoietic Stem Cell Transplantation for Older Patients With Acute Myeloid Leukemia

Opinion statement

Acute myelogenous leukemia (AML) in the elderly is complex and has a poor prognosis, often characterized by higher risk cytogenetic and molecular features compared to that in younger patients. Rates of transplant have been limited by concern related to non-relapse mortality, as older patients have historically been considered medically unfit for the transplantation process. Reduced-intensity conditioning (RIC) for hematopoietic stem cell transplantation (HSCT) has been shown to provide similar efficacy to myeloablative methods, with decreased non-relapse mortality in the elderly and improved efficacy over non-transplant approaches with cytotoxic chemotherapy alone. Targeted non-cytotoxic and modified cytotoxic agents have emerged to further improve transplant outcomes for older AML patients. Validated comorbidity indices are useful tools to assess an individual's fitness for undergoing HSCT rather than chronological age alone. We believe HSCT is the primary curative treatment approach for many older AML patients, taking into account risk and comorbidities, particularly given the tendency of leukemia in this population to harbor an unfavorable disease profile. We use RIC and advocate for the addition of targeted agents if applicable. With continuing data in support of transplant for older AML patients, we anticipate that transplant rates in this population will continue to rise.

https://ift.tt/2D7v7po

Diagnosis and Treatment of Myxoid Liposarcomas: Histology Matters

Opinion statement

Sarcomas are a heterogeneous group of rare malignancies that arise from mesenchymal cells and can occur anywhere in the body. Herein, the focus will be on one subtype of sarcoma that arises from adipocytic tissue, liposarcoma. Specifically, the review will focus on one type of liposarcoma, myxoid liposarcoma. Given the rarity of this tumor, it is imperative that these patients are treated at a sarcoma center, where a multidisciplinary approach incorporates all the modalities available including clinical trials. As the understanding of the biology of myxoid liposarcomas progresses, more targeted therapies are being developed that will lead to better tolerated treatments and improved survival for patients. In this review, we will be discussing the pathophysiology, clinical presentation, diagnostic workup, and available treatment options including surgery, radiation, chemotherapy, and clinical trials.

https://ift.tt/2PjzlQn

Gastrointestinal Dysfunction in Parkinson’s Disease

Abstract

Purpose of review

During the past 25 years, there has been an explosion of information regarding the occurrence of gastrointestinal dysfunction in Parkinson's disease. In this review, the clinical features of gastrointestinal dysfunction in Parkinson's disease will be described and information regarding the potential role of the enteric nervous system and the gut microbiome in the genesis of Parkinson's disease will be addressed.

Recent findings

Recognition is growing regarding the role that gastroparesis and small intestinal dysfunction may play in Parkinson's disease, especially with regard to erratic responses to anti-Parkinson medication. The presence of enteric nervous system involvement in Parkinson's disease is now well established, but whether the enteric nervous system is the starting point for Parkinson's disease pathology remains a source of debate. The potential role of the gut microbiome also is beginning to emerge.

Summary

Gastrointestinal dysfunction is a prominent nonmotor feature of Parkinson's disease and dysfunction can be found along the entire length of the gastrointestinal tract. The enteric nervous system is clearly involved in Parkinson's disease. Whether it is the initial source of pathology is still a source of controversy. There also is growing recognition of the role that the gut microbiome may play in Parkinson's disease, but much more research is needed to fully assess this aspect of the disorder.

https://ift.tt/2q9FYXj

Beyond the hospital infection control guidelines: a qualitative study using positive deviance to characterize gray areas and to achieve efficacy and clarity in the prevention of healthcare-associated infections

The literature is replete with attempts to design and promote customized guidelines to reduce infections during the care continuum. Paradoxically, these efforts sometimes result in gray areas where many staff ...

https://ift.tt/2AqHZ7C

Neuromyelitis optica spectrum disorders with and without connective tissue disorders

Neuromyelitis optica spectrum disorders (NMOSD) often coexist with connective tissue disorders (CTD). The aim of this study was to investigate and compare the features of NMOSD with and without CTD.

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Meet Our Editorial Board Member

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Acknowledgements

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Stromal interleukin-33 promotes regulatory T cell-mediated immunosuppression in head and neck squamous cell carcinoma and correlates with poor prognosis

Abstract

Regulatory T cells (Tregs) mediate immunosuppressive signals that can contribute to the progression of head and neck squamous cell carcinoma (HNSCC). Interleukin-33 (IL-33) is defined as an 'alarmin', an endogenous factor that is expressed during tissue and cell damage, which has been shown to promote Treg proliferation in non-lymphoid organs. However, the interaction between IL-33 and Tregs in the HNSCC tumor microenvironment remains uncertain. In this study, we examined IL-33⁺ and Foxp3⁺ cells by immunohistochemistry in 68 laryngeal squamous cell cancer patients, followed by functional analysis of IL-33 in Tregs. In addition, the suppressive function of Tregs was assessed by cell proliferation assays. The level of stromal IL-33 was significantly upregulated in advanced versus early stage HNSCC patients and positively correlated with Foxp3⁺ Treg infiltration as well as a poor prognosis. ST2 is regarded as the only receptor of IL-33. Infiltrated ST2-expressing Tregs were responsive to IL-33, and the percentage of Tregs was increased upon IL-33 stimulation. Functional investigation demonstrated that IL-33 increased the proportion of Foxp3⁺GATA3⁺ Tregs and improved the suppressive functions of Tregs by inducing IL-10 and TGF-β1 as well as decreasing the proliferation of responder T cells. Blockade of ST2 abrogated the immunosuppression caused by IL-33. Our data demonstrate that stromal IL-33 both expands the Treg population and enhances their functions in the tumor microenvironment. Furthermore, stromal IL-33 has prognostic value for tumor progression. Thus, stromal IL-33 is a potential target for future HNSCC immunotherapy.

https://ift.tt/2PQopXG

The Limits of Measuring Information in Biology: an Ontological Approach

Abstract

The concept of biological information, and information in general, usually presupposes a purely quantitative view of reality. Even though actualist quantification has an important place in the description of the world, a nominalistic stance that tries to simplify reality in purely actualist terms inevitably runs into inconsistencies; these inconsistencies have been pointed out by the critical assessments of the notion of biological information. Rather than calling for an abandonment of the informational terminology, we try to rethink information as a part of an event, the description of which cannot be exhausted by a physicalist, mechanistic, temporally static view of reality. Reconceptualizing the notion of biological information in terms of a process of interpretation rather than as an informational object allows us to transcend the limitations imposed by an analysis of reality that depends on a fixed, finite structure of outcome. Thus, we argue that measuring biological information is intrinsically problematic.

https://ift.tt/2yYE1RC

Pharmacokinetics of clobazam oral soluble film

Epilepsia, EarlyView.

https://ift.tt/2SeTbLf

Stromal interleukin-33 promotes regulatory T cell-mediated immunosuppression in head and neck squamous cell carcinoma and correlates with poor prognosis

Abstract

https://ift.tt/2PQopXG

Hepatocellular carcinoma-associated hypercholesterolemia: involvement of proprotein-convertase-subtilisin-kexin type-9 (PCSK9)

Abstract

Background

PCSK9 regulates low-density lipoprotein cholesterol (LDLc) level and has been implicated in hypercholesterolemia. Aberrant plasma lipid profile is often associated with various cancers. Clinically, the relationship between altered serum lipid level and hepatocellular carcinoma (HCC) has been documented; however, the underlying cause and implications of such dyslipidemia remain unclear.

Methods

The present study includes the use of HepG2 tumor xenograft model to study the potential role of glucose (by providing 15% glucose via drinking water) in regulating PCSK9 expression and associated hypercholesterolemia. To support in vivo findings, in vitro approaches were used by incubating HCC cells in culture medium with different glucose concentrations or treating the cells with glucose uptake inhibitors. Impact of hypercholesterolemia on chemotherapy was demonstrated by exogenously providing LDLc followed by appropriate in vitro assays.

Results

We observed that serum and hepatic PCSK9 level is decreased in mice which were provided with glucose containing water. Interestingly, serum and tumor PCSK9 level was upregulated in HepG2-tumor-bearing mice having access to water containing glucose. Additionally, elevated LDLc is detected in sera of these mice. In vitro studies indicated that PCSK9 expression was increased by high glucose availability with potential involvement of reactive oxygen species (ROS) and sterol regulatory element binding protein-1 (SREBP-1). Furthermore, it is also demonstrated that pre-treatment of cells with LDLc diminishes cytotoxicity of sorafenib in HCC cells.

Conclusion

Taken together, these results suggest a regulation of PCSK9 by high glucose which could contribute, at least partly, towards understanding the cause of hypercholesterolemia in HCC and its accompanied upshots in terms of altered response of HCC cells towards cancer therapy.

https://ift.tt/2AqvKHU

Retention of HIV infected pregnant and breastfeeding women on option B+ in Gomba District, Uganda: a retrospective cohort study

Lifelong antiretroviral therapy for HIV infected pregnant and lactating women (Option B+) has been rapidly scaled up but there are concerns about poor retention of women initiating treatment. However, facility...

https://ift.tt/2PSjAgh

Rising rates of injection drug use associated infective endocarditis in Virginia with missed opportunities for addiction treatment referral: a retrospective cohort study

Injection drug use (IDU) is a growing public health threat in Virginia, though there is limited knowledge of related morbidity. The purpose of this study was to describe the temporal, geographic and clinical t...

https://ift.tt/2Aqv05F

Editorial Board

https://ift.tt/2Ra6hZ1

Early pancreatic cancer — The role of endoscopic ultrasound with or without tissue acquisition in diagnosis and staging

Pancreatic cancer (PC) is one of the deadliest cancers with a 5-year overall survival of less than 6%. Due to its insidious clinical course and unspecific symptoms, the diagnosis is usually late, with only 15–20% patients presenting with potentially curable disease. It is, therefore, extremely important to identify patients with PC at early stages of the disease when tumors may be amenable to surgical resection. For unresectable and borderline resectable PC it is consensual to perform a biopsy to have a cyto/histological confirmation of malignancy before treatment.

https://ift.tt/2OPBX9m

Translation and initial validation of the Medication Adherence Report Scale (MARS) in Italian patients with Crohn’s Disease

The MARS-5 (Medication Adherence Report Scale) was developed in English. The aim of this project was to analyse the MARS-5I (© Prof Rob Horne) psychometric properties and to identify whether its Italian translation is suitable for assessing medication adherence in Crohn Disease (CD) Italian patients. The MARS was translated and linguistically validated in Italian. The MARS-5I was used for evaluating medication adherence in the SOLE study, conducted in Italy on 552 subjects with CD. In order to un-bias the questionnaire results from the effects of treatment change and/or effectiveness, the analyses were performed on the 277 patients whose disease activity remained stable, selected among the 371 patients who maintained the same treatment between two consecutive visits.

https://ift.tt/2Ra6hIv

Intraductal ultrasonographic diagnosis of hydatid membranes in the common bile duct

A 76-year-old Tibetan woman was admitted to us with a one-month history of intermittent abdominal pain, fever and jaundice. There was a history of excision of hepatic hydatid cyst 40 years ago. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a cystic mass in the right lobe of the liver and abnormal material in a dilated common bile duct (CBD), which was demonstrated as a multiple cord-like structure by magnetic resonance cholangiopancreatography (MRCP) (Fig. 1a). Endoscopic retrograde cholangiopancreatography (ERCP) revealed a hugely dilated CBD with irregular filling defects (Fig.

https://ift.tt/2ONZasy

AISF position paper on HCV in immunocompromised patients

This report summarizes the clinical features and the indications for treating HCV infection in immunocompromised and transplanted patients in the Direct Acting Antiviral drugs era.

https://ift.tt/2Rd5CG2

Harmonising proton pump inhibitors treatment in the specialist setting following the SIGE recommendations

we read with great interest the position paper of the Italian Society of Gastroenterology (SIGE) on the appropriateness of prescription for proton pump inhibitor (PPI) drugs that was recently published in Digestive and Liver Disease, as we feel that the statements reported in the manuscript should actually represent a "Dos and don'ts" companion handbook in everyday clinical practice of both primary care physicians and specialists in gastroenterology [1].

https://ift.tt/2OLKaeB

Large abdominopelvic mammary-type myofibroblastoma with incomplete resection and recurrence

A 48-year-old man consulted for vague abdominal discomfort and increased urinary frequency. CT showed a large abdominopelvic mass compressing the urinary bladder, prostate, and rectum (Fig. 1). This lesion was well-demarcated with no involvement of adjacent anatomic structures. Surgery and pathology showed a mammary-type myofibroblastoma (MTM), which was incompletely resected due to its large size. Follow-up CT, a year later, showed a recurring lesion in the pelvis with very slow growth during subsequent 4-year imaging monitoring (Fig.

https://ift.tt/2Ret8Tf

Shortened Lifespan and Other Age-Related Defects in Bang Sensitive Mutants of Drosophila melanogaster

Mitochondrial diseases are complex disorders that exhibit their primary effects in energetically active tissues. Damage generated by mitochondria is also thought to be a key component of aging and age-related disease. An important model for mitochondrial dysfunction is the bang sensitive (bs) mutants in Drosophila melanogaster. Although these mutants all show a striking seizure phenotype, several bs mutants have gene products that are involved with mitochondrial function, while others affect excitability another way. All of the bs mutants (para^bss, eas, jus, ses B, tko are examined here) paralyze and seize upon challenge with a sensory stimulus, most notably mechanical stimulation. These and other excitability mutants have been linked to neurodegeneration with age. In addition to these phenotypes, we have found age-related defects for several of the bs strains. The mutants eas, ses B, and tkodisplay shortened lifespan, an increased mean recovery time from seizure with age, and decreased climbing ability over lifespan as compared to isogenic CS or w¹¹¹⁸lines. Other mutants show a subset of these defects. The age-related phenotypes can be rescued by feeding melatonin, an antioxidant, in all the mutants except ses B. The age-related defects do not appear to be correlated with the seizure phenotype. Inducing seizures on a daily basis did not exacerbate the phenotypes and treatment with antiepileptic drugs did not increase lifespan. The results suggest that the excitability phenotypes and the age-related phenotypes may be somewhat independent and that these phenotypes mutants may arise from impacts on different pathways.

https://ift.tt/2O5CAX9

Highly Continuous Genome Assembly of Eurasian Perch (Perca fluviatilis) Using Linked-Read Sequencing

The Eurasian perch (Perca fluviatilis) is the most common fish of the Percidae family and is widely distributed across Eurasia. Perch is a popular target for professional and recreational fisheries, and a promising freshwater aquaculture species in Europe. However, despite its high ecological, economical and societal importance, the available genomic resources for P. fluviatilis are rather limited. In this work, we report de novo assembly and annotation of the whole genome sequence of perch. The linked-read based technology with 10X Genomics Chromium chemistry and Supernova assembler produced a draft perch genome ~1.0 Gbp assembly (scaffold N₅₀ = 6.3 Mb; the longest individual scaffold of 29.3 Mb; BUSCO completeness of 88.0%), which included 281.6 Mb of putative repeated sequences. The perch genome assembly presented here, generated from small amount of starting material (0.75 ng) and a single linked-read library, is highly continuous and considerably more complete than the currently available draft of P. fluviatilis genome. A total of 23,397 protein-coding genes were predicted, 23,171 (99%) of which were annotated functionally from either sequence homology or protein signature searches. Linked-read technology enables fast, accurate and cost-effective de novo assembly of large non-model eukaryote genomes. The highly continuous assembly of the Eurasian perch genome presented in this study will be an invaluable resource for a range of genetic, ecological, physiological, ecotoxicological, functional and comparative genomic studies in perch and other fish species of the Percidae family.

https://ift.tt/2ywIN9F

Whole-Genome Analysis of Introgression Between the Spotted Owl and Barred Owl (Strix occidentalis and Strix varia, Respectively; Aves: Strigidae) in Western North America

As the barred owl (Strix varia; Aves: Strigiformes: Strigidae) expands throughout western North America, hybridization between barred and spotted owls (Strix varia and S. occidentalis, respectively), if abundant, may lead to genetic swamping of the endangered spotted owl. We analyzed low-coverage, whole-genome sequence data from fifty-one barred and spotted owls to investigate recent introgression between these two species. Although we obtained genomic confirmation that these species can and do hybridize and backcross, we found no evidence of widespread introgression. Plumage characteristics of western S. varia that suggested admixture with S. occidentalis appear unrelated to S. occidentalis ancestry and may instead reflect local selection.

https://ift.tt/2O2B205

RNA-Seq-Based Analysis Reveals Heterogeneity in Mature 16S rRNA 3' Termini and Extended Anti-Shine-Dalgarno Motifs in Bacterial Species

We present an RNA-Seq based approach to map 3' end sequences of mature 16S rRNA (3' TAIL) in bacteria with single-base specificity. Our results show that 3' TAILs are heterogeneous among species; they contain the core CCUCC anti-Shine-Dalgarno motif, but vary in downstream lengths. Importantly, our findings rectify the mis-annotated 16S rRNAs in 11 out of 13 bacterial species studied herein (covering Cyanobacteria, Deinococcus-Thermus, Firmicutes, Proteobacteria, Tenericutes, and Spirochaetes). Furthermore, our results show that species-specific 3' TAIL boundaries are retained due to their high complementarity with preferred Shine-Dalgarno sequences, suggesting that 3' TAIL bases downstream of the canonical CCUCC motif play a more important role in translation initiation than previously reported.

https://ift.tt/2yyQdcd

The NCI Transcriptional Pharmacodynamics Workbench: a tool to examine dynamic expression profiling of therapeutic response in the NCI-60 cell line panel

The intracellular effects and overall efficacies of anticancer therapies can vary significantly by tumor type. To identify patterns of drug-induced gene modulation that occur in different cancer cell types, we measured gene expression changes across the NCI-60 cell line panel after exposure to 15 anticancer agents. The results were integrated into a combined database and set of interactive analysis tools, designated the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), that allows exploration of gene expression modulation by molecular pathway, drug target, and association with drug sensitivity. We identified common transcriptional responses across agents and cell types and uncovered gene expression changes associated with drug sensitivity. We also demonstrated the value of this tool for investigating clinically-relevant molecular hypotheses and identifying candidate biomarkers of drug activity. The NCI TPW, publicly available at https://ift.tt/2As0cl4, provides a comprehensive resource to facilitate understanding of tumor cell characteristics that define sensitivity to commonly used anticancer drugs.

https://ift.tt/2PVgDMe

PIN1 maintains redox balance via the c-Myc/NRF2 axis to counteract Kras-induced mitochondrial respiratory injury in pancreatic cancer cells.

Kras is a decisive oncogene in pancreatic ductal adenocarcinoma (PDAC). PIN1 is a key effector involved in the Kras/ERK axis, synergistically mediating various cellular events. However, the underlying mechanism by which PIN1 promotes the development of PDAC remains unclear. Here we sought to elucidate the effect of PIN1 on redox homeostasis in Kras-driven PDAC. PIN1 was prevalently upregulated in PDAC and predicted the prognosis of the disease, especially Kras-mutant PDAC. Downregulation of PIN1 inhibited PDAC cell growth and promoted apoptosis, partially due to mitochondrial dysfunction. Silencing of PIN1 damaged basal mitochondrial function by significantly increasing intracellular ROS. Furthermore, PIN1 maintained redox balance via synergistic activation of c-Myc and NRF2 to upregulate expression of antioxidant response element (ARE)-driven genes in PDAC cells. This study elucidates a new mechanism by which Kras/ERK/NRF2 promotes tumor growth and identifies PIN1 as a decisive target in therapeutic strategies aimed at disturbing the redox balance in pancreatic cancer.

https://ift.tt/2PXMYC9

Isoform switching as a mechanism of acquired resistance to mutant isocitrate dehydrogenase inhibition [Research Briefs]

Somatic mutations in cytosolic or mitochondrial isoforms of Isocitrate Dehydrogenase (IDH1 or IDH2, respectively) contribute to oncogenesis via production of the metabolite 2-hydroxyglutarate (2HG). Isoform-selective IDH inhibitors suppress 2HG production and induce clinical responses in patients with IDH1- and IDH2-mutant malignancies. Despite the promising activity of IDH inhibitors, the mechanisms that mediate resistance to IDH inhibition are poorly understood. Here, we describe four clinical cases that identify mutant IDH isoform switching, either from mutant IDH1 to mutant IDH2 or vice versa, as a mechanism of acquired clinical resistance to IDH inhibition in solid and liquid tumors.

https://ift.tt/2yWICUc

Development of a best-practice clinical guideline for the use of bleomycin in the treatment of germ cell tumours in the UK

Development of a best-practice clinical guideline for the use of bleomycin in the treatment of germ cell tumours in the UK

Development of a best-practice clinical guideline for the use of bleomycin in the treatment of germ cell tumours in the UK, Published online: 25 October 2018; doi:10.1038/s41416-018-0300-x

Development of a best-practice clinical guideline for the use of bleomycin in the treatment of germ cell tumours in the UK

https://ift.tt/2S9Pk2d

Ten-year results of the PORTEC-2 trial for high-intermediate risk endometrial carcinoma: improving patient selection for adjuvant therapy

Ten-year results of the PORTEC-2 trial for high-intermediate risk endometrial carcinoma: improving patient selection for adjuvant therapy

Ten-year results of the PORTEC-2 trial for high-intermediate risk endometrial carcinoma: improving patient selection for adjuvant therapy, Published online: 25 October 2018; doi:10.1038/s41416-018-0310-8

Ten-year results of the PORTEC-2 trial for high-intermediate risk endometrial carcinoma: improving patient selection for adjuvant therapy

https://ift.tt/2z01l1s

Acute Brucellosis Presenting as an Autoimmune Hemolytic Anemia

Brucellosis is one of the most widespread zoonosis in the world. Hematological complications in brucellosis usually present as mild anemia, leukopenia, or pancytopenia. Autoimmune hemolytic anemia in brucellosis is rarely reported. Here, we report an 18-year-old female presented to us with progressive fatigue, jaundice, and fever. Hematological investigations revealed hemolytic anemia. Direct Coombs test was positive. Further evaluation showed positive serology and culture for Brucella. The patient was diagnosed with brucellosis with autoimmune hemolytic anemia. She was put on rifampicin and doxycycline along with corticosteroids. After 6 weeks, the patient was symptomatically improved with complete remission of hemolytic anemia. The possibility of brucellosis should be considered as a differential diagnosis of autoimmune hemolytic anemia, especially those living in the endemic areas.

https://ift.tt/2CC5ufs

Algorithm-Defined Tx Duration Non-Inferior in Staph Bacteremia

WEDNESDAY, Oct. 24, 2018 -- For patients with staphylococcal bacteremia, an algorithm that defines treatment duration results in a non-inferior rate of clinical success compared with usual care, according to a study published in the Sept. 25 issue...

https://ift.tt/2SiTaWy

FDA Approves First New Influenza Drug in 20 Years

WEDNESDAY, Oct. 24, 2018 -- For the first time in nearly two decades, the U.S. Food and Drug Administration has approved a new type of antiviral influenza drug. The single oral dose of Xofluza (baloxavir marboxil) is for the treatment of...

https://ift.tt/2Sma9HQ

Almost One in 10 Treated in Hospital for Non-Fatal Injury

WEDNESDAY, Oct. 24, 2018 -- In 2013, 9.8 per 100 people were treated in the hospital for a non-fatal injury, with costs estimated at $1.853 trillion, according to a study published online Oct. 8 in Injury Epidemiology. Mark R. Zonfrillo, M.D., from...

https://ift.tt/2z0TXTk

7 Children Dead From Adenovirus Outbreak in New Jersey

WEDNESDAY, Oct. 24, 2018 -- New Jersey health officials on Wednesday confirmed the deaths of seven children after infection with an adenovirus. Eleven other children are infected, and all cases occurred at the same health care facility, the Wanaque...

https://ift.tt/2z0TWie

Tibia Lead Levels Linked to Risk of Resistant-Hypertension

WEDNESDAY, Oct. 24, 2018 -- Tibia lead levels are associated with resistant-hypertension (HTN), according to a study published online Oct. 24 in the Journal of the American Heart Association. Alexander Zheutlin, from the University of Michigan in...

https://ift.tt/2SdFGM5

Reflections on Thyroid Autoimmunity: A Personal Overview from the Past into the Future

Horm Metab Res
DOI: 10.1055/a-0725-9297

After investigating thyroid autoimmunity for more than 40 years, we present a personal perspective on the field. Despite effective therapies for Graves' hyperthyroidism and Hashimoto's thyroiditis, cures are elusive. Novel forms of therapy are being developed, such as small molecule inhibitors of the TSH receptor (TSHR), but cure will require immunotherapy. This goal requires advances in understanding the pathogenesis of thyroid autoimmunity, the 'keys' for which are the thyroid antigens themselves. Presently, however, greater investigative focus is on non-thyroid specific immune cell types and molecules. Thyroid autoantigens are the drivers of the autoimmune response, a prime example being the TSHR. In our view, the TSHR is the culprit as well as the victim in Graves' disease because of its unique structure. Unlike the closely related gonadotropin receptors, the TSHR cleaves into subunits and there is strong evidence that its shed extracellular A-subunit, not the holoreceptor, is the major antigen driving pathogenic thyroid stimulating autoantibodies (TSAb) development. There is no Graves' disease of the gonads. Studies of potential antigen-specific immunotherapies require an animal model. Such models have been developed in which TSAb can be induced or, more importantly, arise spontaneously. Not appreciated until recently by thyroid investigators is that B cell surface autoantibodies are highly efficient 'antigen receptors' and the epitope to which an autoantibody binds influences antigen processing and which peptide is presented to T cells. These animal models and recombinant human autoantibodies cloned from Graves' and Hashimoto's B cells (plasma cells) are available for study by future generations.
[...]

Article in Thieme eJournals:
Table of contents | Abstract | Full text

https://ift.tt/2D0Hnbn

Development of the perceived barriers scale: a new instrument identifying barriers to career development and employment for young adult survivors of pediatric CNS tumors

Abstract

Purpose

Given the significant employment disparities for survivors of pediatric brain tumors, there is increased need to conduct vocational and career research with this group. The purpose of the present study was to construct an instrument, the Perceived Barriers Scale, that is psychometrically sound and has both clinical and research application related to career and employment issues of pediatric brain tumor survivors.

Method

The participants consisted of 110 young adult central nervous system survivors of childhood cancer aged between 18 and 30 years old (M = 23.05, SD = 3.36) who were identified by the DFCI Pediatric Brain Tumor Clinic. The 12-item Perceived Barriers Scale was developed from a comprehensive literature review, clinical interviews conducted with survivors of pediatric brain tumors, and feedback from multidisciplinary providers. Exploratory factor analysis and correlations were completed to examine the initial psychometric properties of the scale.

Results

Exploratory factors analysis identified two factors that accounted for 57.92% with the two factors labeled as internal barriers and external barriers. All factors loaded significantly onto their respective factors (.48 to .88). The results of the correlational analysis found significant relationships between both internal barrier and external barrier subscales and CSE and WHODAS-2 providing initial support for the construct validity of the Perceived Barriers Scale.

Conclusions

Overall, the study findings indicate good psychometrics with the brevity of the scale increasing potential application and utilization in both research and clinical settings.

Implications for cancer survivors

Identification of employment barriers for brain tumor survivors provides opportunity for more targeted vocational intervention.

https://ift.tt/2EJSZRt

Crestline’s Specialty Vehicle Division introduces new Patient Transport Unit

SASKATOON, SK, Canada — Crestline Coach, a global leader in ambulance and specialty vehicle manufacturing and a Canadian distributor of small to mid-sized buses, announced the recent addition of the Crestline manufactured Patient Transport Unit to its portfolio of specialty vehicle solutions. Crestline designed the Patient Transport Unit to bridge the gap between health care and long-term...

https://ift.tt/2SlDCSe

Ten-year results of the PORTEC-2 trial for high-intermediate risk endometrial carcinoma: improving patient selection for adjuvant therapy

https://ift.tt/2ApHOtd

Development of a best-practice clinical guideline for the use of bleomycin in the treatment of germ cell tumours in the UK

https://ift.tt/2PUb8xl

Keratoacanthoma Centrifugum Marginatum with Spontaneous Regression and Its Possible Differential Diagnosis

Keratoacanthoma centrifugum marignatum (KCM) is a rare variant of keratoacanthoma, which is characterized by the dense infiltration of inflammatory cells throughout the dermis, especially around the keratinocytic islands. Therefore, it is sometimes difficult to differentiate between KCM and cutaneous T-cell lymphomas. In this report, we describe a case of KCM with spontaneous regression that showed dense infiltration of CD3+CD8+ T cells. Our present case suggested the importance of investigating tumor-infiltrating lymphocytes to avoid the misdiagnosis of KCM as cutaneous T-cell lymphoma.
Case Rep Oncol 2018;11:671–675

https://ift.tt/2yvOvZ5

Optimal Timing of Repeat Newborn Screening for Congenital Hypothyroidism in Preterm Infants to Detect Delayed Thyroid-Stimulating Hormone Elevation

To evaluate the timing of a delayed rise in thyroid-stimulating hormone (TSH) levels in preterm infants with congenital hypothyroidism, and to determine whether cases of congenital hypothyroidism would be missed by using current consensus guidelines of repeat screening at approximately 2 weeks of age or 2 weeks after the first screening.

https://ift.tt/2ONiczi

Plasma miR-1290 Is a Novel and Specific Biomarker for Early Diagnosis of Necrotizing Enterocolitis—Biomarker Discovery with Prospective Cohort Evaluation

To discover specific circulating microRNA (miRNA) biomarkers for the early differentiation of necrotizing enterocolitis (NEC) from neonatal sepsis and inflammatory conditions.

https://ift.tt/2RefSOC

Anti-Müllerian Hormone in Girls with Premature Adrenarche: The Impact of Polycystic Ovary Syndrome History in their Mothers

To assess whether the serum levels of anti-Müllerian hormone (AMH) are increased in girls with premature adrenarche because they are at a higher risk of developing polycystic ovary syndrome (PCOS) later in life.

https://ift.tt/2ONifes

Assessment of Malnutrition Risk in Canadian Pediatric Hospitals: A Multicenter Prospective Cohort Study

To assess the prevalence, causes, and consequences of malnutrition, as well as the evolution of nutritional status, in Canadian pediatric health care institutions.

https://ift.tt/2RfbnDn

Epilepsy and Neurodegeneration: Clues in the Hair and Blood Vessels!

A 4-month-old boy, born to nonconsanguineous parents, presented with daily, recurrent seizures. The initial focal, motor seizures evolved into clustered, flexor type of infantile spasms at 7 months of age and became polymorphic by 15 months of age. He had global developmental delay with a developmental age of 3-4 months. Additionally, he lost head control with progression and required repeated hospitalizations for pneumonia. He was the third child born in the family with an unremarkable perinatal period.

https://ift.tt/2RefX4S

Learning of robust spectral graph dictionaries for distributed processing

We consider the problem of distributed representation of signals in sensor networks, where sensors exchange quantized information with their neighbors. The signals of interest are assumed to have a sparse repr...

https://ift.tt/2Aq7Axy

Braun Ambulances to Display Four Units at EMS World Expo 2018

The ambulance manufacturer will showcase what it means to be Built for Life with two new ambulances showcased next to a five-year-old unit and a remounted unit VAN WERT, Ohio — Braun Ambulances will be attending EMS World Expo October 29-November 2, 2018. The ambulance manufacturer will display four ambulances, including two Nashville ambulances, a Jacksonville unit, and a remounted New...

https://ift.tt/2ShHl2V

Loss of first baby tooth a positive experience for children

Scared, ashamed, happy or proud -- how do children feel when they lose their first baby tooth? Scientists have now found that children's feelings are predominantly positive. The study also reveals that previous visits to the dentist's as well as parental background and level of education affect how children experience the loss of their first tooth.

https://ift.tt/2SexvyU

Large-scale Top-down Proteomics Using Capillary Zone Electrophoresis Tandem Mass Spectrometry

A detailed protocol is described for the separation, identification, and characterization of proteoforms in protein samples using capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry (CZE-ESI-MS/MS). The protocol can be used for the high-resolution characterization of proteoforms in simple protein samples and the large-scale identification of proteoforms in complex proteome samples.

https://ift.tt/2O5RaxE

A Rat Methyl-Seq Platform to Identify Epigenetic Changes Associated with Stress Exposure

Here, we describe the protocol and implementation of Methyl-Seq, an epigenomic platform, using a rat model to identify epigenetic changes associated with chronic stress exposure. Results demonstrate that the rat Methyl-Seq platform is capable of detecting methylation differences that arise from stress exposure in rats.

https://ift.tt/2OM4Umw

Visualization of Tangential Cell Migration in the Developing Chick Optic Tectum

We describe the methods for fluorescent labeling of tangentially migrating cells by electroporation, and for time-lapse imaging of the labeled cell movement in a flat-mount culture in order to visualize migrating cell behavior in the developing chick optic tectum.

https://ift.tt/2O3SEIW

Inhibitory functions of PD-L1 and PD-L2 in the regulation of anti-tumor immunity in murine tumor microenvironment

Abstract

Although a role of PD-L1 in the suppression of anti-tumor immunity and its value as a predictive biomarker has been suggested by various preclinical and clinical studies, the precise mechanisms how PD-L1 and PD-L2, another ligand of PD-1, regulate anti-tumor immunity in the tumor microenvironment are yet to be fully explored. Here, we address this issue using PD-L1-deficient tumor cells, PD-L1-knockout (KO) mice, anti-PD-L1 monoclonal antibody (mAb), and anti-PD-L2 mAb. Firstly, PD-L1-deficient or competent tumor cells were inoculated into wild-type or PD-L1-KO mice. Results of tumor growth and mouse survival indicated that both tumor- and host-derived PD-L1 are functional to suppress anti-tumor immunity, while the former contributes predominantly than the latter. Experiments using bone marrow (BM) chimeric mice, generated by transferring PD-L1-KO BM cells into wild-type mice or vice versa, further suggested that PD-L1 expressed on BM-derived hematopoietic cells mediates the suppressive effects on anti-tumor immunity. Secondly, anti-PD-L2 mAb treatment demonstrated a profound synergy with anti-PD-L1 mAb therapy, whereas anti-PD-L2 mAb alone hardly induced any anti-tumor effects, suggesting that PD-L2's function becomes evident when the effects of PD-L1 are abrogated by anti-PD-L1 mAb. Consistent with this notion, PD-L2 expression was upregulated on tumor-associated macrophages (TAM) when mice were treated with anti-PD-L1 mAb. Taken together, our study elucidated the importance of PD-L1 associated with tumor cells and non-tumor host cells, particularly BM-derived hematopoietic cells, as well as PD-L2 inducibly expressed on TAM in the suppression of anti-tumor immunity in the tumor microenvironment.

https://ift.tt/2CCo7zM

Efficient and Scalable Directed Differentiation of Clinically Compatible Corneal Limbal Epithelial Stem Cells from Human Pluripotent Stem Cells

This protocol introduces a simple two-step method for differentiating corneal limbal epithelial stem cells from human pluripotent stem cells under xeno- and feeder cell-free culture conditions. The cell culture methods presented here enable cost-efficient, large-scale production of clinical quality cells applicable to corneal cell therapy use.

https://ift.tt/2Rc27j9

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice

Here we present the unpredictable chronic mild stress protocol in mice. This protocol induces a long-term depressive-like phenotype and enables to assess the efficacy of putative antidepressants in reversing the behavioral and neuromolecular depressive-like deficits.

https://ift.tt/2q8B3pB

Deep Neural Network Improves Detection of Wrist Fractures

WEDNESDAY, Oct. 24, 2018 -- Deep learning methods allow senior medical specialists to deliver their expertise to emergency medicine clinicians via use of a deep neural network, which is associated with considerable improvement in sensitivity and...

https://ift.tt/2qaAM5s

Prevalence of Pediatric Metabolic, Bariatric Surgery Examined

WEDNESDAY, Oct. 24, 2018 -- From 2005 through 2014, an estimated 14,178 metabolic and bariatric surgery (MBS) procedures were performed among pediatric patients aged 20 years and younger with severe obesity, according to a research letter published...

https://ift.tt/2Rds6a5

Hispanics With HIV Face Higher Risk for HPV-Related Cancer

WEDNESDAY, Oct. 24, 2018 -- HIV-infected Hispanics have an increased risk for human papillomavirus (HPV)-related cancers than Hispanics in the general population, according to a study published online Oct. 22 in Cancer. Ana P. Ortiz, Ph.D., from the...

https://ift.tt/2qaAL1o

Most Supplements Contain Prohibited Stimulants

WEDNESDAY, Oct. 24, 2018 -- Many supplements contain one or more stimulants that have been the subject of U.S. Food and Drug Administration-issued public notices, according to a research letter published online Oct. 22 in JAMA Internal...

https://ift.tt/2ReOgsB

Arthritis in Adulthood Linked to Childhood Maltreatment

WEDNESDAY, Oct. 24, 2018 -- The prevalence of arthritis is higher among adults who experience severe and/or frequent childhood maltreatment, according to a study published online Oct. 17 in Arthritis Care & Research. Elizabeth M. Badley,...

https://ift.tt/2qc6y1T

High-Dose Flu Vaccine May Cut Hospitalization in Dialysis Patients

WEDNESDAY, Oct. 23, 2018 -- Receipt of the high-dose influenza vaccine in 2016 to 2017 was associated with lower rates of hospitalization among dialysis patients, according to a study published online Oct. 23 in the Clinical Journal of the American...

https://ift.tt/2RcB9bg

Midwifery Care Cuts Poor Birth Outcomes Versus Physician Care

WEDNESDAY, Oct. 24, 2018 -- Compared with physician models of care, midwifery care is associated with lower odds of poor birth outcomes for low-income women, according to a study published in the October issue of BMJ Open. In a study of 57,872...

https://ift.tt/2qaAI5I

Health Enterprise Zone Initiative Cut Hospitalizations, Costs

WEDNESDAY, Oct. 24, 2018 -- Maryland's Health Enterprise Zone Initiative reduced hospitalizations and led to net cost savings, according to a study published in the October issue of Health Affairs. Darrell J. Gaskin, Ph.D., from the Johns Hopkins...

https://ift.tt/2RbRlcH

Myo-Inositol Does Not Reduce Retinopathy of Prematurity

WEDNESDAY, Oct. 24, 2018 -- Treatment with myo-inositol for up to 10 weeks does not reduce the risk for type 1 retinopathy of prematurity (ROP) or death versus placebo for premature infants younger than 28 weeks of gestational age, according to a...

https://ift.tt/2qaAGuC

AGA Issues Guidelines for Opioid-Induced Constipation

WEDNESDAY, Oct. 24, 2018 -- Recommendations for medical management of opioid-induced constipation include laxatives as first-line agents, according to a guideline from the American Gastroenterological Association (AGA) published online Oct. 17 in...

https://ift.tt/2Rcqopf

Inhibitory functions of PD-L1 and PD-L2 in the regulation of anti-tumor immunity in murine tumor microenvironment

Abstract

https://ift.tt/2CCo7zM

Neuronal Response Latencies Encode First Odor Identity Information across Subjects

Odorants are coded in the primary olfactory processing centers by spatially and temporally distributed patterns of glomerular activity. Whereas the spatial distribution of odorant-induced responses is known to be conserved across individuals, the universality of its temporal structure is still debated. Via fast two-photon calcium imaging, we analyzed the early phase of neuronal responses in the form of the activity onset latencies in the antennal lobe projection neurons of honeybee foragers. We show that each odorant evokes a stimulus-specific response latency pattern across the glomerular coding space. Moreover, we investigate these early response features for the first time across animals, revealing that the order of glomerular firing onsets is conserved across individuals and allows them to reliably predict odorant identity, but not concentration. These results suggest that the neuronal response latencies provide the first available code for fast odor identification.

SIGNIFICANCE STATEMENT Here, we studied early temporal coding in the primary olfactory processing centers of the honeybee brain by fast imaging of glomerular responses to different odorants across glomeruli and across individuals. Regarding the elusive role of rapid response dynamics in olfactory coding, we were able to clarify the following aspects: (1) the rank of glomerular activation is conserved across individuals, (2) its stimulus prediction accuracy is equal to that of the response amplitude code, and (3) it contains complementary information. Our findings suggest a substantial role of response latencies in odor identification, anticipating the static response amplitude code.

https://ift.tt/2R95nvR

Anterior Temporal Lobectomy Impairs Neural Classification of Body Emotions in Right Superior Temporal Sulcus and Reduces Emotional Enhancement in Distributed Brain Areas without Affecting Behavioral Classification

Humans with amygdalar lesions show proportional reductions of the emotional response to facial expressions in the fusiform face area as well as deficits in emotion recognition from facial expressions. While processing of bodily expressions shares many similarities with facial expressions, there is no substantial evidence that lesions of the amygdala result in similar behavioral and neural sequelae. We combined behavioral assessment with functional neuroimaging in a group of male and female humans with unilateral anterior temporal lobe (ATL) resections, including the amygdala (right: n = 10; left: n = 10) and 12 matched controls. The objective was to assess whether the amygdala is crucial for the recognition of body expressions and for modulatory effects on distant areas during perception of body expressions. The behavioral results revealed normal performance in both patient groups on emotion categorization of body expressions. The neuroimaging results showed that ATL patients displayed no enhanced activations in right fusiform body area and left extrastriate body area and that left ATL patients additionally displayed no enhanced activations in right posterior superior temporal sulcus and right extrastriate body area, respectively. Multivoxel pattern analysis revealed altered categorization capacity between emotional and neutral stimuli in right posterior superior temporal sulcus in right ATL patients. In addition, we also found emotional enhancement in frontal, parietal, occipital, and cingulate regions in controls. Together, our data show that the amygdala and ATLs are not necessary for recognition of dynamic body expressions, but suggest that amygdala lesions affect body emotion processing in distant brain areas.

SIGNIFICANCE STATEMENT For humans, information from emotional expressions of others is crucial to support social interactions. The majority of emotion studies has focused on facial expressions; however, in daily life, we also use information from body postures and body movement. Visual processing of body expressions relies on a brain network, including body-specific visual areas and visuomotor areas. Even though the importance of the amygdala and its modulatory effects on distant brain regions have been documented, it remains unclear whether the amygdala plays a crucial role in emotional body processing. By combining behavioral and neuroimaging data in patients with amygdalar lesions, we provide further evidence for its modulatory effect on distant areas during the perception of body expressions.

https://ift.tt/2RcoTaB

Cortical Potentials Evoked by Subthalamic Stimulation Demonstrate a Short Latency Hyperdirect Pathway in Humans

A monosynaptic projection from the cortex to the subthalamic nucleus is thought to have an important role in basal ganglia function and in the mechanism of therapeutic subthalamic deep-brain stimulation, but in humans the evidence for its existence is limited. We sought physiological confirmation of the cortico-subthalamic hyperdirect pathway using invasive recording techniques in patients with Parkinson's disease (9 men, 1 woman). We measured sensorimotor cortical evoked potentials using a temporary subdural strip electrode in response to low-frequency deep-brain stimulation in patients undergoing awake subthalamic or pallidal lead implantations. Evoked potentials were grouped into very short latency (<2 ms), short latency (2–10 ms), and long latency (10–100 ms) from the onset of the stimulus pulse. Subthalamic and pallidal stimulation resulted in very short-latency evoked potentials at 1.5 ms in the primary motor cortex accompanied by EMG-evoked potentials consistent with corticospinal tract activation. Subthalamic, but not pallidal stimulation, resulted in three short-latency evoked potentials at 2.8, 5.8, and 7.7 ms in a widespread cortical distribution, consistent with antidromic activation of the hyperdirect pathway. Long-latency potentials were evoked by both targets, with subthalamic responses lagging pallidal responses by 10–20 ms, consistent with orthodromic activation of the thalamocortical pathway. The amplitude of the first short-latency evoked potential was predictive of the chronic therapeutic stimulation contact.

SIGNIFICANCE STATEMENT This is the first physiological demonstration of the corticosubthalamic hyperdirect pathway and its topography at high spatial resolution in humans. We studied cortical potentials evoked by deep-brain stimulation in patients with Parkinson's disease undergoing awake lead implantation surgery. Subthalamic stimulation resulted in multiple short-latency responses consistent with activation of hyperdirect pathway, whereas no such response was present during pallidal stimulation. We contrast these findings with very short latency, direct corticospinal tract activations, and long-latency responses evoked through polysynaptic orthodromic projections. These findings underscore the importance of incorporating the hyperdirect pathway into models of human basal ganglia function.

https://ift.tt/2OPIVLp

Klotho modulates ER-mediated signaling crosstalk between prosurvival autophagy and apoptotic cell death during LPS challenge

Abstract

Bacterial endotoxins have been shown to induce prosurvival autophagy or apoptosis in fibroblasts and thus impair the wound healing process. Endoplasmic reticulum has been proposed as a molecular switch between these processes and klotho protein possessing pleiotropic characteristics seems to be involved in both processes, however the exact molecular mechanism is unknown. In this study, we have evaluated the effect of klotho silencing on human fibroblasts exposed to a non-toxic dose of lipopolysaccharide in terms of in vitro wound healing ability. We show for the first time, that klotho silencing in fibroblasts intensified lipopolysaccharide-induced oxidative stress and inflammatory response, what resulted in genomic instability, p-eIF2a-mediated ER stress, retardation of prosurvival autophagy, induction of apoptotic cell death and finally in impaired wound closure. Therefore, our data suggest that klotho serves as a part of cellular defense mechanism engaged in providing protection against bacterial infections during wound healing by modulating ER-signaling crosstalk between autophagy and apoptosis.

https://ift.tt/2PRSAxB

Convergent Metabotropic Signaling Pathways Inhibit SK Channels to Promote Synaptic Plasticity in the Hippocampus

Hebbian synaptic plasticity at hippocampal Schaffer collateral synapses is tightly regulated by postsynaptic small conductance (SK) channels that restrict NMDA receptor activity. SK channels are themselves modulated by G-protein-coupled signaling pathways, but it is not clear under what conditions these are activated to enable synaptic plasticity. Here, we show that muscarinic M1 receptor (M1R) and type 1 metabotropic glutamate receptor (mGluR1) signaling pathways, which are known to inhibit SK channels and thereby disinhibit NMDA receptors, converge to facilitate spine calcium transients during the induction of long-term potentiation (LTP) at hippocampal Schaffer collateral synapses onto CA1 pyramidal neurons of male rats. Furthermore, mGluR1 activation is required for LTP induced by reactivated place-cell firing patterns that occur in sharp-wave ripple events during rest or sleep. In contrast, M1R activation is required for LTP induced by place-cell firing patterns during exploration. Thus, we describe a common mechanism that enables synaptic plasticity during both encoding and consolidation of memories within hippocampal circuits.

SIGNIFICANCE STATEMENT Memory ensembles in the hippocampus are formed during active exploration and consolidated during rest or sleep. These two distinct phases each require strengthening of synaptic connections by long-term potentiation (LTP). The neuronal activity patterns in each phase are very different, which makes it hard to map generalized rules for LTP induction onto both formation and consolidation phases. In this study, we show that inhibition of postsynaptic SK channels is a common necessary feature of LTP induction and that SK channel inhibition is achieved by separate but convergent metabotropic signaling pathways. Thus, we reveal a common mechanism for enabling LTP under distinct behavioral conditions.

https://ift.tt/2OKyM2B

CACHD1 is an {alpha}2{delta}-Like Protein That Modulates CaV3 Voltage-Gated Calcium Channel Activity

The putative cache (Ca²⁺ channel and chemotaxis receptor) domain containing 1 (CACHD1) protein has predicted structural similarities to members of the α2 voltage-gated Ca²⁺ channel auxiliary subunit family. CACHD1 mRNA and protein were highly expressed in the male mammalian CNS, in particular in the thalamus, hippocampus, and cerebellum, with a broadly similar tissue distribution to Ca_V3 subunits, in particular Ca_V3.1. In expression studies, CACHD1 increased cell-surface localization of Ca_V3.1, and these proteins were in close proximity at the cell surface, consistent with the formation of CACHD1-Ca_V3.1 complexes. In functional electrophysiological studies, coexpression of human CACHD1 with Ca_V3.1, Ca_V3.2, and Ca_V3.3 caused a significant increase in peak current density and corresponding increases in maximal conductance. By contrast, α2-1 had no effect on peak current density or maximal conductance in Ca_V3.1, Ca_V3.2, or Ca_V3.3. A comparison of CACHD1-mediated increases in Ca_V3.1 current density and gating currents revealed an increase in channel open probability. In hippocampal neurons from male and female embryonic day 19 rats, CACHD1 overexpression increased Ca_V3-mediated action potential firing frequency and neuronal excitability. These data suggest that CACHD1 is structurally an α2-like protein that functionally modulates Ca_V3 voltage-gated calcium channel activity.

SIGNIFICANCE STATEMENT This is the first study to characterize the Ca²⁺ channel and chemotaxis receptor domain containing 1 (CACHD1) protein. CACHD1 is widely expressed in the CNS, in particular in the thalamus, hippocampus, and cerebellum. CACHD1 distribution is similar to that of low voltage-activated (Ca_V3, T-type) calcium channels, in particular to Ca_V3.1, a protein that regulates neuronal excitability and is a potential therapeutic target in conditions such as epilepsy and pain. CACHD1 is structurally an α2-like protein that functionally increases Ca_V3 calcium current. CACHD1 increases the presence of Ca_V3.1 at the cell surface, forms complexes with Ca_V3.1 at the cell surface, and causes an increase in channel open probability. In hippocampal neurons, CACHD1 causes increases in neuronal firing. Thus, CACHD1 represents a novel protein that modulates Ca_V3 activity.

https://ift.tt/2OKQMtU

The Divalent Metal Transporter 1 (DMT1) Is Required for Iron Uptake and Normal Development of Oligodendrocyte Progenitor Cells

The divalent metal transporter 1 (DMT1) is a multimetal transporter with a primary role in iron transport. Although DMT1 has been described previously in the CNS, nothing was known about the role of this metal transporter in oligodendrocyte maturation and myelination. To determine whether DMT1 is required for oligodendrocyte progenitor cell (OPC) maturation, we used siRNAs and the Cre-lox system to knock down/knock out DMT1 expression in vitro as well as in vivo. Blocking DMT1 synthesis in primary cultures of OPCs reduced oligodendrocyte iron uptake and significantly delayed OPC development. In vivo, a significant hypomyelination was found in DMT1 conditional knock-out mice in which DMT1 was postnatally deleted in NG2- or Sox10-positive OPCs. The brain of DMT1 knock-out animals presented a decrease in the expression levels of myelin proteins and a substantial reduction in the percentage of myelinated axons. This reduced postnatal myelination was accompanied by a decrease in the number of myelinating oligodendrocytes and a rise in proliferating OPCs. Furthermore, using the cuprizone model of demyelination, we established that DMT1 deletion in NG2-positive OPCs lead to less efficient remyelination of the adult brain. These results indicate that DMT1 is vital for OPC maturation and for the normal myelination of the mouse brain.

SIGNIFICANCE STATEMENT To determine whether divalent metal transporter 1 (DMT1), a multimetal transporter with a primary role in iron transport, is essential for oligodendrocyte development, we created two conditional knock-out mice in which DMT1 was postnatally deleted in NG2- or Sox10-positive oligodendrocyte progenitor cells (OPCs). We have established that DMT1 is necessary for normal OPC maturation and is required for an efficient remyelination of the adult brain. Since iron accumulation by OPCs is indispensable for myelination, understanding the iron incorporation mechanism as well as the molecules involved is critical to design new therapeutic approaches to intervene in diseases in which the myelin sheath is damaged or lost.

https://ift.tt/2RaL01i

Stac Proteins Suppress Ca2+-Dependent Inactivation of Neuronal L-type Ca2+ Channels

Stac protein (named for its SH3- and cysteine-rich domains) was first identified in brain 20 years ago and is currently known to have three isoforms. Stac2, Stac1, and Stac3 transcripts are found at high, modest, and very low levels, respectively, in the cerebellum and forebrain, but their neuronal functions have been little investigated. Here, we tested the effects of Stac proteins on neuronal, high-voltage-activated Ca²⁺ channels. Overexpression of the three Stac isoforms eliminated Ca²⁺-dependent inactivation (CDI) of l-type current in rat neonatal hippocampal neurons (sex unknown), but not CDI of non-l-type current. Using heterologous expression in tsA201 cells (together with β and α₂-₁ auxiliary subunits), we found that CDI for Ca_V1.2 and Ca_V1.3 (the predominant, neuronal l-type Ca²⁺ channels) was suppressed by all three Stac isoforms, whereas CDI for the P/Q channel, Ca_V2.1, was not. For Ca_V1.2, the inhibition of CDI by the Stac proteins appeared to involve their direct interaction with the channel's C terminus. Within the Stac proteins, a weakly conserved segment containing ~100 residues and linking the structurally conserved PKC C1 and SH3_1 domains was sufficient to fully suppress CDI. The presence of CDI for l-type current in control neonatal neurons raised the possibility that endogenous Stac levels are low in these neurons and Western blotting indicated that the expression of Stac2 was substantially increased in adult forebrain and cerebellum compared with neonate. Together, our results indicate that one likely function of neuronal Stac proteins is to tune Ca²⁺ entry via neuronal l-type channels.

SIGNIFICANCE STATEMENT Stac protein, first identified 20 years ago in brain, has recently been found to be essential for proper trafficking and function of the skeletal muscle l-type Ca2+ channel and is the site of mutations causing a severe, inherited human myopathy. In neurons, however, functions for Stac protein have remained unexplored. Here, we report that one likely function of neuronal Stac proteins is tuning Ca2+ entry via l-type, but not that via non-l-type, Ca2+ channels. Moreover, there is a large postnatal increase in protein levels of the major neuronal isoform (Stac2) in forebrain and cerebellum, which could provide developmental regulation of l-type channel Ca2+ signaling in these brain regions.

https://ift.tt/2RdNJqW

Veno-Venous Extracorporeal Membrane Oxygenation in a Mouse

Here we present a protocol describing the technique of veno-venous extracorporeal membrane oxygenation (ECMO) in a non-intubated, spontaneously breathing mouse. This murine model of ECMO can be effectively implemented in experimental studies of acute and end-stage lung diseases.

https://ift.tt/2q8C29a

Fabrication and Testing of Photonic Thermometers

We describe the process of fabrication and testing of photonic thermometers.

https://ift.tt/2CCSS7F

Penfield’s stimulation for direct cortical motor mapping: An outdated technique?

Neurosurgeons worldwide are indebted to Dr. Wilder Penfield for his seminal work on intraoperative cortical mapping. Although Penfield was not the first to apply electrical current to the human brain in Neurosurgery - Robert Bartholow's case dates back to 1874 (Bartholow, 1874) -, he certainly pioneered the development of cortical stimulation into a routine neurosurgical procedure (Ladino et al., 2018). The original work by Penfield and Boldrey in 1937 reads: "Stimulation is carried out by either unipolar or bipolar platinum electrodes which emerge from a glass handle and are attached to insulated wires […] In recent years we have found a thyratron stimulator […] and have usually employed a wave frequency of from 55 to 65 per second […] The current is thus constant and may be altered accurately in rate and intensity" (Penfield and Boldrey, 1937).

https://ift.tt/2CCFoJ2

Approaches to Sleep in Severely Brain Damaged Patients – Further comments and replies to Kotchoubey & Pavlov

We would like to further contribute to the discussion regarding circadian rhythms in patients with disorders of consciousness (DOC; Kotchoubey and Pavlov, 2018a,b; Rossi Sebastiano et al., 2018; Rossi Sebastiano and Franceschetti, 2018; Schabus et al., 2018). Specifically, we would like to respond to Kotchoubey and Pavlov (2018b) and clarify remaining issues and misunderstandings that seem to have arisen from our previous comment (Schabus et al., 2018).

https://ift.tt/2q9ehOx

Machine learning versus human expertise: the case of sleep stage classification in Disorders of Consciousness. Response to Wislowska et al

The discussion published in several Letters in Clinical Neurophysiology appears to be productive because consensus has been attained regarding most questions except one. This is the question of whether automatic methods of the analysis of sleep stages can, or actually do, outperform scoring by human experts. As regards the former part of the question (i.e., whether they can), we agree that the answer should be positive. As regards the latter part (i.e., whether they already do), some hesitations remain.

https://ift.tt/2CAXNpK

Non-invasive brain stimulation in the modulation of cerebral blood flow after stroke: a systematic review of Transcranial Doppler studies

NIBS has been successfully explored as a biomarker and therapeutic adjunct for functional recovery after stroke. rTMS and tDCS are two such promising neuromodulatory techniques that have been widely investigated to prime the motor areas of the brain in combination with task-specific practice (Bastani et al., 2012, Hsu et al., 2012, Jodie et al., 2015, Le et al., 2014). Although these techniques have demonstrated modest efficacy, clinical translation is still limited as the underlying physiological mechanisms are not completely understood, nor is the inter-individual variability associated with these techniques resolved (López-Alonso et al., 2014, Maeda et al., 2000, Wiethoff et al., 2014).

https://ift.tt/2q73XX0

Heart rate variability in neonatal patients with seizures

Seizures are the most common alterations observed in neurological conditions affecting newborns (Evans and Levene, 1998). Due to its larger excitability, the developing brain is more prone to seizures than the mature brain (Holmes and Ben-Ari, 1998; Lawrence and Inder, 2010; Levene, 2002; Nardou et al., 2013). The incidence of neonatal seizures (NS) is about 1 to 3 per 1000 live births, but this estimate increases when preterm infants are included (Vasudevan and Levene, 2013). NS are generally related to serious brain conditions (e.g.

https://ift.tt/2CCFnEY

Delirium is not associated with altered hub flexibility of the posterior cingulate cortex

Delirium is an acute disturbance of attention, awareness and cognition that tends to fluctuate over time. It is an acute and serious condition, affecting more than 15% of all hospitalized patients, and is related to poor outcomes such as prolonged length of hospital stay and long-term cognitive impairment. Although previous studies suggest multiple hypotheses towards underlying mechanisms, e.g. neurotransmitter imbalances, abnormal stress response and neuroinflammation, the exact pathogenesis of delirium remains poorly understood.

https://ift.tt/2q9e79T

T-LAK cell-originated protein kinase (TOPK): an emerging target for cancer-specific therapeutics

T-LAK cell-originated protein kinase (TOPK): an emerging target for cancer-specific therapeutics

T-LAK cell-originated protein kinase (TOPK): an emerging target for cancer-specific therapeutics, Published online: 24 October 2018; doi:10.1038/s41419-018-1131-7

T-LAK cell-originated protein kinase (TOPK): an emerging target for cancer-specific therapeutics

https://ift.tt/2yvmuAT

Reprogramming mechanisms influence the maturation of hematopoietic progenitors from human pluripotent stem cells

Reprogramming mechanisms influence the maturation of hematopoietic progenitors from human pluripotent stem cells

Reprogramming mechanisms influence the maturation of hematopoietic progenitors from human pluripotent stem cells, Published online: 24 October 2018; doi:10.1038/s41419-018-1124-6

Reprogramming mechanisms influence the maturation of hematopoietic progenitors from human pluripotent stem cells

https://ift.tt/2ER3kLM

A 3-Dimensional Mapping Analysis of Regional Nodal Recurrences in Breast Cancer

We analyzed the anatomic pattern of nodal recurrence among a large number of breast cancer patients and provide evidence-based contouring guidelines, in addition to analysis of pathologic factors specifically associated with recurrence in the supraclavicular, axillary, and internal mammary regions.

https://ift.tt/2D3ouUS

The American Society for Radiation Oncology 2017 Radiation Oncologist Workforce Study

The ASTRO 2017 radiation oncologist workforce survey showed, relative to the 2012 survey, narrowing of the gender gap, greater racial diversity, and increased concern about RO oversupply. ROs reported median 250 consults and 20 on-treatment patients in 2016, and increase in time allocation to electronic health record management. Job vacancies were more prevalent in urban practices and academic/university systems. Practice merger/buyout was the lead reason for ROs to change employer. ROs are gravitating towards urban and suburban locations at the expense of rural locations. The workforce has shifted from private practice predominance to more equal balance with academic/university systems.

https://ift.tt/2EKsD21

Natural Course of Asymptomatic Walled Off Pancreatic Necrosis

There is paucity of data on natural course of asymptomatic walled off necrosis (WON).

https://ift.tt/2EG2yAY

Plasma and brain pharmacokinetics of letrozole and drug interaction studies with temozolomide in NOD- scid gamma mice and sprague dawley rats

Abstract

Purpose

The aromatase inhibitor, letrozole, is being investigated in experimental animal models as a novel treatment for high-grade gliomas (HGGs). To facilitate optimal dosing for such studies, we evaluated the plasma and brain pharmacokinetics (PK) of letrozole in NOD-scid gamma (NSG) mice, which are frequently employed for assessing efficacy against patient-derived tumor cells. Furthermore, we evaluated the potential PK interactions between letrozole and temozolomide (TMZ) in Sprague–Dawley rats.

Methods

NSG mice were administered letrozole (8 mg/kg; i.p) as a single or multiple dose (b.i.d, 10 days). Brain tissue and blood samples were collected over 24 h. Letrozole and TMZ interaction study employed jugular vein-cannulated rats (three groups; TMZ alone, letrozole alone and TMZ + letrozole). Intracerebral microdialysis was performed for brain extracellular fluid (ECF) collection simultaneously with venous blood sampling. Drug levels were measured employing HPLC and PK analysis was conducted using Phoenix WinNonlin^®.

Results

In NSG mice, peak plasma and brain tissue letrozole concentrations (C_max) were 3–4 and 0.8–0.9 µg/ml, respectively. The elimination half-life was 2.6 h with minimal accumulation following multiple dosing. In the drug interaction study, no PK changes were evident when TMZ and letrozole were given in combination. For instance, peak plasma and brain ECF TMZ levels when given alone were 14.7 ± 1.1 and 4.6 ± 0.6 µg/ml, respectively, and 12.6 ± 2.4 and 3.4 ± 0.8 µg/ml, respectively, when given with letrozole.

Conclusions

These results will guide the optimization of dosing regimen for further development of letrozole for HGG treatment.

https://ift.tt/2OJoCPQ

Response to “Hyoscine butylbromide for the management of death rattle: sooner rather than later”

We have read with interest the paper by Mercadante et al [1] and congratulate the authors on completing this work in a group notoriously hard to study. While the outcomes of the study at face value support the regular use of anticholinergics to reduce the phenomena of noisy secretions, we believe the routine use of medications is not supported within the available evidence.

https://ift.tt/2z103mQ

Pilot Qualitative Study of Informal Teachers in Interprofessional Collaboration and Practice

Non-physician members of the interprofessional palliative care team often participate in teaching physicians and others in the context of workplace learning due to the interprofessional collaborative nature of the specialty.

https://ift.tt/2Se4yDe

Author's Response

I'm grateful for the interesting comments by an authoritative group of researchers from Australia. I'm trying to respond point by point.

https://ift.tt/2z10qxK

Novel Computer-assisted Diagnosis System for Endoscopic Disease Activity in Patients with Ulcerative Colitis

Evaluation of endoscopic disease activity for patients with ulcerative colitis (UC) is important when determining the treatment of choice. However, endoscopists require a certain period of training to evaluate the activity of inflammation properly, and interobserver variability exists. Therefore, we constructed a computer-assisted diagnosis (CAD) system using a convolutional neural network (CNN) and evaluated its performance using a large data set of endoscopic images from patients with UC.

https://ift.tt/2EHtd09

Αρχειοθήκη ιστολογίου

Αναζήτηση αυτού του ιστολογίου

Τετάρτη 24 Οκτωβρίου 2018

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