Using Social Media at National Meetings in Hematology—Optimal Use, Tips, Strategies, and Limitations

Abstract

Social media has become an important tool for physicians and scientists to rapidly share information with colleagues around the world. Use of social media outlets—in particular, Twitter—has risen rapidly in recent years, and it is now customary for national hematology meetings to have thousands of participants who share photographs and textual summaries of data presentations, as well as personal insights and commentary, with virtual audiences. These messages, or "tweets," can be specifically followed using a hashtag ontology which arose organically over the past several years in the context of medical meetings. This system facilitates communication between meeting attendees and those colleagues near and far with similar interests, thus globalizing the conversation between hematology providers, investigators, patient advocates, professional organizations, regulatory agencies, testing companies, and the pharmaceutical industry about cutting-edge developments in the field.

http://ift.tt/2yRaDhH

Rhabdomyolysis: a 10-year retrospective study of patients treated in a medical department.

Background: Rhabdomyolysis is a common and potentially life-threatening syndrome, and acute kidney injury (AKI) is a serious complication. We performed a 10-year retrospective study that included all patients treated for rhabdomyolysis in a medical clinic. We examined the relationships between the levels of creatine kinase (CK), myoglobin, and creatinine (as a marker of renal function and thereby AKI), and whether the myoglobin/CK ratio could be a valuable tool in the clinical evaluation of this patient group. Clinical characteristics were noted. Patients and methods: The study included all patients treated for rhabdomyolysis in the Department of Medicine, Oslo University Hospital Ulleval, from 2003 to 2012. Rhabdomyolysis was defined as a serum CK activity more than five times the upper reference limit. Results: A total of 341 patients were included in the study; 51% developed AKI, and 20% of those required dialysis. Logistic regression showed that myoglobin concentration [P

http://ift.tt/2zQHEbV

The influence of grasping habits and object orientation on motor planning in children and adults

Abstract

We investigated the influence of habitual grasp strategies and object orientation on motor planning in 3-year-olds and 4- to 5-year-old children and adults. Participants were required to rotate different vertically oriented objects around 180°. Usually, adults perform this task by grasping objects with an awkward grip (thumb and index finger pointing downward) at the beginning of the movement, in order to finish it with a comfortable hand position. This pattern corresponds to the well-known end-state comfort effect (ESC) in grasp planning. The presented objects were associated with different habitual grasp orientations that either corresponded with the grasp direction required to reach end-state comfort (downward) or implied a contrary grasp orientation (upward). Additionally, they were presented either in their usual, canonical orientation (e.g., shovel with the blade oriented downward versus cup with its opening oriented upward) or upside down. As dependent variable we analyzed the number of grips conforming to the end-state comfort principle (ESC score) realized in each object type and orientation condition. The number of grips conforming to ESC strongly increased with age. In addition, the extent to which end-state comfort was considered was influenced by the actual orientation of the objects' functional parts. Thus, in all age-groups the ESC score was highest when the functional parts of the objects were oriented downward (shovel presented canonically with blade pointing downward, cup presented upside down) and corresponded to the hand orientation needed to realize ESC.

http://ift.tt/2i6zST6

Behavioral flexibility in learning to sit

Abstract

What do infants learn when they learn to sit upright? We tested behavioral flexibility in learning to sit—the ability to adapt posture to changes in the environment—in 6- to 9-month-old infants sitting on forward and backward slopes. Infants began with slant at 0°; then slant increased in 2° increments until infants lost balance. Infants kept balance on impressively steep slopes, especially in the forward direction, despite the unexpected movements of the apparatus. Between slant adjustments while the slope was stationary, infants adapted posture to the direction and degree of slant by leaning backward on forward slopes and forward on backward slopes. Postural adaptations were nearly optimal for backward slopes. Sitting experience predicted greater postural adaptations and increased ability to keep balance on steeper changes of slant, but only for forward slopes. We suggest that behavioral flexibility is integral to learning to sit and increases with sitting experience.

http://ift.tt/2gF7lUB

Sensitivity to facial expressions among extremely low birth weight survivors in their 30s

The current study investigated the impact of birth weight on the ability to recognize facial expressions in adulthood among the longest known prospectively followed cohort of extremely low birth weight survivors (ELBW; <1,000 g). We measured perceptual threshold to detect subtle facial expressions and confusion among different emotion categories in order to disentangle visual perceptual ability from emotional processing. ELBW adults (N = 64, M_age = 31.9 years) were more likely than normal birth weight (NBW) controls (N = 82, M_age = 32.5 years) to see fear in angry faces. This finding was not a result of increased perceptual efficiency in processing fearful expressions in the ELBW adults, since the two groups did not differ on their threshold to detect emotion in low intensity facial expressions. These findings suggest that a processing bias toward fear may reflect long-term developmental effects from being born at ELBW that may portend socioemotional problems that characterize ELBW survivors.

http://ift.tt/2i4UNGk

Vigilance for threat accounts for inter-individual variation in physiological responses to adversity in rhesus macaques: A cognition × environment approach

Abstract

Early life adversity (ELA) can lead to poor health later in life. However, there is significant variation in outcomes, with some individuals displaying resilience even in the face of adversity. Using longitudinal data collected from free-ranging rhesus macaques between birth and 3 years, we examined whether individual variation in vigilance for threat, an early emerging attentional bias, can account for variation in long-term outcomes between individuals reared in similar environments. We found that ELA and vigilance during infancy interact to predict physiological dysregulation in Sympathetic Nervous System (SNS) and Hypothalamic-Pituitary-Adrenal (HPA) stress responses during juvenility. During high stress periods, High ELA juveniles with high vigilance exhibit less asymmetry than High ELA juveniles with low vigilance. This suggests that although increased vigilance is viewed as a negative consequence of ELA, it might also be a mechanism by which vulnerable individuals proactively buffer themselves from negative outcomes in unstable or threatening environments.

http://ift.tt/2gF7ibn

Sexual orientation identity and tobacco and hazardous alcohol use: findings from a cross-sectional English population survey

Objectives

To assess the association between tobacco and hazardous alcohol use and sexual orientation and whether such an association could be explained by other sociodemographic characteristics.

Design

Cross-sectional household survey conducted in 2014–2016.

Setting

England, UK.

Participants

Representative English population sample (pooled n=43 866).

Main outcomes

Sexual orientation identity (lesbian/gay, bisexual, heterosexual, prefer-not-to-say); current tobacco and hazardous alcohol use (defined as Alcohol Use Disorders Identification Test Score ≥8). All outcomes were self-reported.

Results

Due to interactions between sexual orientation and gender for substance use, analyses were stratified by gender. Tobacco use prevalence was significantly higher among lesbian/gay (women: 24.9%, 95% CI 19.2% to 32.6%; men: 25.9%, 95% CI 21.3% to 31.0%) and bisexual participants (women: 32.4%, 95% CI 25.9% to 39.6%; men: 30.7%, 95% CI 23.7% to 30.7%) and significantly lower for prefer-not-to-say participants in women (15.5%, 95% CI 13.5% to 17.8%) but not men (22.7%, 95% CI 20.3% to 25.3%) compared with heterosexual participants (women: 17.5%, 95% CI 17.0% to 18.0%; men: 20.4%, 95% CI 19.9% to 21.0%; p<0.001 for omnibus test). Similarly, hazardous alcohol use was significantly more prevalent for lesbian/gay (women: 19.0%, 95% CI 14.0% to 25.3%; men: 30.0%, 25.2%–35.3%) and bisexual participants (women: 24.4%, 95% CI 18.7% to 31.3%; men: 24.3%, 95% CI 17.9% to 32.1%) and lower for prefer-not-to-say participants (women: 4.1%, 95% CI 3.0% to 5.4%; men: 13.7%; 95% CI 11.8% to 16.0%) compared with heterosexuals (women: 8.3%, 95% CI 7.9% to 8.7%; men: 18.4%, 95% CI 17.9% to 18.9%; p<0.001 for omnibus test). However, after adjusting for sociodemographic confounders, tobacco use was similar across all sexual orientation groups among both women and men. By contrast, sexual orientation differences in hazardous alcohol use remained even after adjustment among women but not for bisexual and gay men.

Conclusions

In England, higher rates of tobacco use among sexual minority men and women appear to be attributable to other sociodemographic factors. Higher rates of hazardous alcohol use among sexual minority men may also be attributable to these factors, whereas this is not the case for sexual minority women.

http://ift.tt/2zPUgQB

Euthanasia and physician-assisted suicide not meeting due care criteria in the Netherlands: a qualitative review of review committee judgements

AbstractObjectives

To assess how Dutch regional euthanasia review committees (RTE) apply the euthanasia and physician-assisted suicide (EAS) due care criteria in cases where the criteria are judged not to have been met ('due care not met' (DCNM)) and to evaluate how the criteria function to set limits in Dutch EAS practice.

Design

A qualitative review using directed content analysis of DCNM cases in the Netherlands from 2012 to 2016 published on the RTE website (http://ift.tt/2zQybkI) as of 31 January 2017.

Results

Of 33 DCNM cases identified (occurring 2012–2016), 32 cases (97%) were published online and included in the analysis. 22 cases (69%) violated only procedural criteria, relating to improper medication administration or inadequate physician consultation. 10 cases (31%) failed to meet substantive criteria, with the most common violation involving the no reasonable alternative (to EAS) criterion (seven cases). Most substantive cases involved controversial elements, such as EAS for psychiatric disorders or 'tired of life', in incapacitated patients or by physicians from advocacy organisations. Even in substantive criteria cases, the RTE's focus was procedural. The cases were more about unorthodox, unprofessional or overconfident physician behaviours and not whether patients should have received EAS. However, in some cases, physicians knowingly pushed the limits of EAS law. Physicians from euthanasia advocacy organisations were over-represented in substantive criteria cases. Trained EAS consultants tended to agree with or facilitate EAS in DCNM cases. Physicians and families had difficulty applying ambiguous advance directives of incapacitated patients.

Conclusion

As a retrospective review of physician self-reported data, the Dutch RTEs do not focus on whether patients should have received EAS, but instead primarily gauge whether doctors conducted EAS in a thorough, professional manner. To what extent this constitutes enforcement of strict safeguards, especially when cases contain controversial features, is not clear.

http://ift.tt/2xnJ2kw

Cognitive complexity of clients and counsellors during motivation-based treatment for smoking cessation: an observational study on occasional smokers in a US college sample

Objective

Motivational interviewing (MI) is a widely used and promising treatment approach for aiding in smoking cessation. The present observational study adds to other recent research on why and when MI works by investigating a new potential mechanism: integrative complexity.

Setting

The study took place in college fraternity and sorority chapters at one large midwestern university.

Participants

Researchers transcribed MI counselling sessions from a previous randomised controlled trial focused on tobacco cessation among college students and subsequently scored clients' and counsellors' discussions across four counselling sessions for integrative complexity.

Interventions

This is an observational secondary analysis of a randomised controlled trial that tested the effectiveness of MI. We analysed the relationship between integrative complexity and success at quitting smoking in the trial.

Primary and secondary outcome measures

Success in quitting smoking:Participants were categorised into two outcome groups (successful quitters vs failed attempters), created based on dichotomous outcomes on two standard variables: (1) self-reported attempts to quit and (2) number of days smoked via timeline follow-back assessment procedures that use key events in participants' lives to prompt their recall of smoking.

Results

We found (1) significantly higher complexity overall for participants who tried to quit but failed compared with successful quitters (standardised β=0.36, p<0.001, (Lower Confidence Interval.)LCI=0.16, (Upper Confidence Interval) UCI=0.47) and (2) the predictive effect of complexity on outcome remains when controlling for standard motivational and demographic variables (partial r(102)=–0.23, p=0.022).

Conclusions

Taken together, these results suggest that cognitive complexity is uniquely associated with successful quitting in MI controlled trials, and thus may be an important variable to more fully explore during treatment.

http://ift.tt/2xnJ0Jq

Development and pilot testing of a decision aid for the initiation of antipsychotic medications in persons with dementia in long-term care using a systematic approach: a study protocol

Introduction

Antipsychotic medications are commonly used in long-term care to treat neuropsychiatric symptoms of dementia despite concerns that their risks (eg, infection, falls, death) may outweigh their benefits. This study protocol outlines the development and pilot testing of a decision aid for antipsychotic medications that is tailored to the information needs of residents with dementia in long-term care and family caregivers (or decision makers). The goals of the decision aid are to help residents and caregivers (1) better understand the risks and benefits of antipsychotic medications in long-term care, and (2) make informed decisions about their use (or non-use).

Methods and analysis

This multiphased study is being conducted between October 2016 and September 2018. In phase I, the decision aid will be developed after consultation with a steering group, review of scientific evidence on outcomes associated with pharmacological treatments for neuropsychiatric symptoms of dementia in long-term care, review of guidelines for the use of antipsychotic medications in long-term care, and review of guidelines for writing health information for patients and families. The decision aid will also be alpha-tested and redrafted, as necessary, in phase I. In phase II, implementation and reporting guidelines for the decision aid will be developed in collaboration with Directors of Care in long-term care. In phase III, the decision aid will be (1) beta-tested with residents with dementia in long-term care and caregivers not involved in the design phase, and (2) assessed by an external panel of experts.

Ethics and dissemination

Ethical approval for this study has been granted by the Research Ethics Board at the University of Saskatchewan, approval number Beh 16-465. Findings from this study will be disseminated via conference presentations, publications, presentations to policy makers and plain language summaries to residents with dementia in long-term care and their caregivers.

http://ift.tt/2zQ3Um8

Projecting diabetes prevalence among Mexicans aged 50 years and older: the Future Elderly Model-Mexico (FEM-Mexico)

Objective

Diabetes has been growing as a major health problem and a significant burden on the population and on health systems of developing countries like Mexico that are also ageing fast. The goal of the study was to estimate the future prevalence of diabetes among Mexico's older adults to assess the current and future health and economic burden of diabetes.

Design

A simulation study using longitudinal data from three waves (2001, 2003 and 2012) of the Mexican Health and Aging Study and adapting the Future Elderly Model to simulate four scenarios of hypothetical interventions that would reduce diabetes incidence and to project the future diabetes prevalence rates among populations 50 years and older.

Participants

Data from 14 662 participants with information on self-reported diabetes, demographic characteristics, health and mortality.

Outcome measures

We obtained, for each scenario of diabetes incidence reduction, the following summary measures for the population aged 50 and older from 2012 to 2050: prevalence of diabetes, total population with diabetes, number of medical visits.

Results

In 2012, there were approximately 20.7 million persons aged 50 and older in Mexico; 19.3% had been diagnosed with diabetes and the 2001–2003 diabetes incidence was 4.3%. The no-intervention scenario shows that the prevalence of diabetes is projected to increase from 19.3% in 2012 to 34.0% in 2050. Under the 30% incidence reduction scenario, the prevalence of diabetes will be 28.6% in 2050. Comparing the no-intervention scenario with the 30% and 60% diabetes incidence reduction scenarios, we estimate a total of 816 320 and 1.6 million annual averted cases of diabetes, respectively, for the year 2020.

Discussion

Our study underscores the importance of diabetes as a disease by itself and also the potential healthcare demands and social burden of this disease and the need for policy interventions to reduce diabetes prevalence.

http://ift.tt/2zR8Pn6

Bridging knowledge, policies and practices across the ageing and disability fields: a protocol for a scoping review to inform the development of a taxonomy

Introduction

Bridging is a term used to describe activities, or tasks, used to promote collaboration and knowledge exchange across fields. This paper reports the protocol for a scoping review which aims to identify and characterise peer reviewed evidence describing bridging activities, between the ageing and disability fields. The purpose is to clarify the concepts underpinning bridging to inform the development of a taxonomy, and identify research strengths and gaps.

Methods

A scoping review will be conducted. We will search Medline, Cumulative Index to Nursing and Allied Health Literature, Embase, PsycInfo, Sociological Abstracts and the Cochrane Library, to identify peer reviewed publications (reviews, experimental, observational, qualitative designs and expert commentaries) describing bridging activities. Grey literature, and articles not published in English will be excluded. Two investigators will independently complete article selection and data abstraction to minimise bias. A data extraction form will be iteratively developed and information from each publication will be extracted: (1) bibliographic, (2) methodological, (3) demographic, and (4) bridging information. Qualitative content analysis will be used to describe key concepts related to bridging.

Conclusions

To our knowledge, this will be the first scoping review to describe bridging of ageing and disability knowledge, services and policies. The findings will inform the development of a taxonomy to define models of bridging that can be implemented and further evaluated to enable integrated care and improve systems and services for those ageing with disability.

Ethics and dissemination

Ethics is not required because this is a scoping review of published literature. Findings will be disseminated through stakeholder meetings, conference presentations and peer reviewed publication.

http://ift.tt/2xnIM52

An enquiry based on a standardised questionnaire into knowledge, awareness and preferences concerning the care of familial hypercholesterolaemia among primary care physicians in the Asia-Pacific region: the "Ten Countries Study"

Objective

To determine physicians' knowledge, awareness and preferences regarding the care of familial hypercholesterolaemia (FH) in the Asia-Pacific region.

Setting

A formal questionnaire was anonymously completed by physicians from different countries/regions in the Asia-Pacific. The survey sought responses relating to general familiarity, awareness of management guidelines, identification (clinical characteristics and lipid profile), prevalence and inheritance, extent of elevation in risk of cardiovascular disease (CVD) and practice on screening and treatment.

Participants

Practising community physicians from Australia, Japan, Malaysia, South Korea, Philippines, Hong Kong, China, Vietnam and Taiwan were recruited to complete the questionnaire, with the UK as the international benchmark.

Primary outcome

An assessment and comparison of the knowledge, awareness and preferences of FH among physicians in 10 different countries/regions.

Results

1078 physicians completed the questionnaire from the Asia-Pacific region; only 34% considered themselves to be familiar with FH. 72% correctly described FH and 65% identified the typical lipid profile, with a higher proportion of physicians from Japan and China selecting the correct FH definition and lipid profile compared with those from Vietnam and Philippines. However, less than half of the physician were aware of national or international management guidelines; this was significantly worse than physicians from the UK (35% vs 61%, p<0.001). Knowledge of prevalence (24%), inheritability (41%) and CVD risk (9%) of FH were also suboptimal. The majority of the physicians considered laboratory interpretative commenting as being useful (81%) and statin therapy as an appropriate cholesterol-lowering therapy (89%) for FH management.

Conclusions

The study identified important gaps, which are readily addressable, in the awareness and knowledge of FH among physicians in the region. Implementation of country-specific guidelines and extensive work in FH education and awareness programmes are imperative to improve the care of FH in the region.

http://ift.tt/2zR8QYc

Lung function at term in extremely preterm-born infants: a regional prospective cohort study

Objectives

To compare lung function of extremely preterm (EP)-born infants with and without bronchopulmonary dysplasia (BPD) with that of healthy term-born infants, and to determine which perinatal characteristics were associated with lung function at term and how predictive these measurements were for later respiratory health in EP-born infants.

Methods

Perinatal variables were recorded prospectively, and tidal breathing parameters were measured at term-equivalent age using electromagnetic inductance plethysmography. Respiratory morbidity was defined by hospital readmissions and/or treatment with asthma medications during the first year of life.

Results

Fifty-two EP-born infants (mean gestational age 26¹, range 22⁶–27⁶ weeks) and 45 term-born infants were included. There was evidence of significant airway obstruction, higher tidal volumes and increased minute ventilation in the EP-born infants with and without BPD, although generally more pronounced for those with BPD. Male gender, antenatal steroids and number of days on continuous positive airway pressure were associated with lung function outcomes at term. A prediction model incorporating two unrelated tidal breathing parameters, BPD, birth weight z-score and gender, predicted respiratory morbidity in the first year of life with good accuracy (area under the curve 0.818, sensitivity and specificity 81.8% and 75.0%, respectively).

Conclusion

Lung function measured at term-equivalent age was strikingly abnormal in EP-born infants, irrespective of BPD. Tidal breathing parameters may be of value in predicting future pulmonary health in infants born premature.

Trial registration number

NCT01150396; Results.

http://ift.tt/2xnIJpS

Bi-modal stimulation in the treatment of tinnitus: a study protocol for an exploratory trial to optimise stimulation parameters and patient subtyping

Introduction

Tinnitus is the perception of sound in the absence of a corresponding external acoustic stimulus. Bimodal neuromodulation is emerging as a promising treatment for this condition. The main objectives of this study are to investigate the relevance of interstimulus timing and the choices of acoustic and tongue stimuli for a proprietary bimodal (auditory and somatosensory) neuromodulation device, as well as to explore whether specific subtypes of patients are differentially responsive to this novel intervention for reducing the symptoms of chronic tinnitus.

Methods and analysis

This is a two-site, randomised, triple-blind, exploratory study of a proprietary neuromodulation device with a pre–post and 12-month follow-up design. Three different bimodal stimulation parameter sets will be examined. The study will enrol 342 patients, split 80:20 between two sites (Dublin, Ireland and Regensburg, Germany), to complete 12 weeks of treatment with the device. Patients will be allocated to one of three arms using a stepwise stratification according to four binary categories: tinnitus tonality, sound level tolerance (using loudness discomfort level of <60 dB SL as an indicator for hyperacusis), hearing thresholds and presence of a noise-induced audiometric profile. The main indicators of relative clinical efficacy for the three different parameter sets are two patient-reported outcomes measures, the Tinnitus Handicap Inventory and the Tinnitus Functional Index, after 12 weeks of intervention. Clinical efficacy will be further explored in a series of patient subtypes, split by the stratification variables and by presence of a somatic tinnitus. Evidence for sustained effects on the psychological and functional impact of tinnitus will be followed up for 12 months. Safety data will be collected and reported. A number of feasibility measures to inform future trial design include: reasons for exclusion, completeness of data collection, attrition rates, patient's adherence to the device usage as per manufacturer's instructions and evaluation of alternative methods for estimating tinnitus impact and tinnitus loudness.

Ethics and dissemination

This study protocol is approved by the Tallaght Hospital/St. James's Hospital Joint Research Ethics Committee in Dublin, Ireland, and by the Ethics Committee of the University Clinic Regensburg, Germany. Findings will be disseminated to relevant research, clinical, health service and patient communities through publications in peer-reviewed and popular science journals and presentations at scientific and clinical conferences.

Trial registration number

The trial is registered on ClinicalTrials.gov (NCT02669069) Pre-results.

http://ift.tt/2zPXFPc

How do workplaces, working practices and colleagues affect UK doctors career decisions? A qualitative study of junior doctors career decision making in the UK

Objectives

This study draws on an in-depth investigation of factors that influenced the career decisions of junior doctors.

Setting

Junior doctors in the UK can choose to enter specialty training (ST) programmes within 2 years of becoming doctors. Their specialty choices contribute to shaping the balance of the future medical workforce, with views on general practice (GP) careers of particular interest because of current recruitment difficulties. This paper examines how experiences of medical work and perceptions about specialty training shape junior doctors' career decisions.

Participants

Twenty doctors in the second year of a Foundation Training Programme in England were recruited. Purposive sampling was used to achieve a diverse sample from respondents to an online survey.

Results

Narrative interviewing techniques encouraged doctors to reflect on how experiences during medical school and in medical workplaces had influenced their preferences and perceptions of different specialties. They also spoke about personal aspirations, work priorities and their wider future.

Junior doctors' decisions were informed by knowledge about the requirements of ST programmes and direct observation of the pressures under which ST doctors worked. When they encountered negative attitudes towards a specialty they had intended to choose, some became defensive while others kept silent. Achievement of an acceptable work-life balance was a central objective that could override other preferences.

Events linked with specific specialties influenced doctors' attitudes towards them. For example, findings confirmed that while early, positive experiences of GP work could increase its attractiveness, negative experiences in GP settings had the opposite effect.

Conclusions

Junior doctors' preferences and perceptions about medical work are influenced by multiple intrinsic and extrinsic factors and experiences. This paper highlights the importance of understanding how perceptions are formed and preferences are developed, as a basis for generating learning and working environments that nurture students and motivate their professional careers.

http://ift.tt/2zOahq5

Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis

Abstract

Patients undergoing radiation therapy for the head and neck are susceptible to a significant and often abrupt deterioration in their oral health. The oral morbidities of radiation therapy include but are not limited to an increased susceptibility to dental caries and periodontal disease. They also include profound and often permanent functional and sensory changes involving the oral soft tissue. These changes range from oral mucositis experienced during and soon after treatment, mucosal opportunistic infections, neurosensory disorders, and tissue fibrosis. Many of the oral soft tissue changes following radiation therapy are difficult challenges to the patients and their caregivers and require life-long strategies to alleviate their deleterious effect on basic life functions and on the quality of life. We discuss the presentation, prognosis, and management strategies of the dental structure and oral soft tissue morbidities resulting from the administration of therapeutic radiation in head and neck patient. A case for a collaborative and integrated multidisciplinary approach to the management of these patients is made, with specific recommendation to include knowledgeable and experienced oral health care professionals in the treatment team.

Oral complications of radiation therapy to the head and neck can result in acute and long-term deterioration in oral soft tissues and dentition. The presentation, prognosis, and strategies to manage the dental and nondental morbidities of radiation therapy to the head and neck are discussed in this manuscript.

http://ift.tt/2zEiQCV

Cancer Registry follow-up for 17 million person-years of a nationwide maternity cohort

Abstract

Population-based Finnish Maternity Cohort (FMC) comprises 2M first trimester sera collected from 1M women during 33 years. Informed consent is by the opt-out principle, and linkages with cancer and population registries provide a base for over time and over generation studies. Follow-up for 17M person-years by the end of 2014 can identify 39,700 cases of invasive cancer and 18,900 cases of premalignant breast and cervix lesions, and basal cell carcinoma diagnosed after serum sampling. For women with multiple pregnancies, serial samples taken before cancer diagnosis are available. Offspring of the women have developed more than 4000 cancers. For 100,000 individuals, samples taken during the pregnancies of both their mothers and grandmothers enable familial cancer studies. FMC continues to collect samples, and surveillance of exposures or interventions like vaccination programs is feasible. In summary, the FMC is a unique, accessible biobank for epidemiological, biomarker, and surveillance studies on cancer.

We announce a biobank comprising virtually the entire population of Finnish females, who have been pregnant since 1983. The Finnish Maternity Cohort (FMC) is linkable with population-based health registers including the Finnish Cancer Registry. Serial prediagnostic serum samples and comprehensive data accessible over three generations provide possibilities for unique study settings. Selected examples on the use of the FMC in cancer studies hopefully stimulate international quest for this open access resource.

http://ift.tt/2h9v7bO

Primary and heterotrophic productivity relate to multikingdom diversity in a hypersaline mat

Abstract

Benthic microbial ecosystems are widespread yet knowledge gaps still remain on the relationships between the diversity of species across kingdoms and productivity. Here, we ask two fundamental questions: (i) How does species diversity relate to the rates of primary and heterotrophic productivity? (ii) How do diel variations in light-energy inputs influence productivity and microbiome diversity? To answer these questions, microbial mats from a magnesium sulfate hypersaline lake were used to establish microcosms. Both the number and relatedness between bacterial and eukaryotic taxa in the microbiome were assayed via amplicon-based sequencing of 16S and 18S rRNA genes over two diel cycles. These results correlated with biomass productivity obtained from substrate-specific ¹³C stable isotope tracers that enabled comparisons between primary and heterotrophic productivity. Both bacterial and eukaryotic species richness and evenness were related only to the rates of ¹³C-labeled glucose and acetate biomass incorporation. Interestingly, measures of these heterotrophic relationships changed from positive and negative correlations depending on carbon derived from glucose or acetate, respectively. The bacterial and eukaryotic diversity of this ecosystem is also controlled, in part, from energy constraints imposed by changing irradiance over a diel cycle.

http://ift.tt/2kWQwJC

Bar versus ball attachments for implant-supported overdentures in complete edentulism: A systematic review

Abstract

Background

Implant-supported overdenture is one of the most predictable treatment options used in complete edentulism. However, differences have been reported between bar and ball attachments used to retain overdentures in terms of patient satisfaction and prosthesis retention.

Purpose

The purpose of this study is to compare the effectiveness of bar and ball attachments for conventionally loaded implant-supported overdentures in completely edentulous patients to improve patient satisfaction and prosthesis retention.

Materials and methods

We conducted the review according to the Cochrane methods and following MECIR standards. We searched Cochrane Oral Health Group Trial register, Cochrane Central Register of Controlled Trials, MEDLINE, and the WHO ICTRP (March 31, 2017). Two review authors assessed trials for inclusion and risk of bias, extracted data, and checked for accuracy. We have expressed results as risk ratio or mean differences, together with their 95% confidence intervals.

Results

We included 10 trials (465 participants). After 5 y, one trial reported higher patient satisfaction when bar attachment was used (MD 1.30, 95% CI 0.20–2.40), and reported no difference between both systems in prosthesis retention (MD −0.90, 95% CI −1.90 to 0.10). Two trials reported no implant failures after 1 and 5 y in both attachments. Downgrading of evidence was based on the unclear risk of bias of included studies and the wide CI crossing the line of no effect.

Conclusions

There is insufficient evidence to support bar or ball attachment to be used with implant-supported overdentures in completely edentulous patients to improve patient satisfaction and prosthesis retention (PROSPERO 2014:CRD42014014594).

http://ift.tt/2zFeVWJ

Hospice Exposure Is Associated with Lower Healthcare Expenditures in Taiwanese Cancer Decedents’ Last Year of Life: A Population-Based Retrospective Cohort Study

Evidence for the association of hospice exposure with lower healthcare expenditures at end of life (EOL) remains inconclusive and neglects EOL care being concentrated in patients' last few months.

http://ift.tt/2gNmbMh

A Case of “Total Nausea:” An Interprofessional Approach to the Management of Chemotherapy-Induced Nausea/Vomiting Complicated by Anxiety and Existential Distress

Total pain, first described in 1964 by Dame Cicely Saunders, took into account the spiritual, psychosocial, practical, and emotional stressors that contribute to a person's experience of pain 1. Although a similar framework has been described for conceptualizing nausea and vomiting, it has not been formally studied and is not as readily considered in clinical practice. Nausea/vomiting is one of the most distressing symptoms following chemotherapy, affecting up to 90% of patients receiving highly emetogenic chemotherapy 2.

http://ift.tt/2yN4406

Dietary Patterns and Cardiovascular Disease Prevention among Patients with Diabetes

Abstract

Purpose of Review

This review summarizes the most recent literature on dietary patterns and their effects on cardiovascular health among patients with diabetes.

Recent Findings

Studies identified examined low-fat, low-carbohydrate, low-glycemic index, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean dietary patterns. A limited number of short-term studies showed that intake of low-fat, low-carbohydrate, and low-glycemic index dietary patterns reduced body weight and blood pressure among individuals with diabetes. Short-term consumption of the DASH dietary pattern reduced blood pressure, low-density lipoprotein cholesterol, and triglyceride levels in patients with diabetes. Most convincing evidence supports the effectiveness of Mediterranean dietary patterns in cardiovascular disease prevention by reducing cardiovascular risk factors and mortality among patients with diabetes, as supported by a prospective cohort study, randomized controlled trials, and meta-analyses.

Summary

Among the dietary patterns identified, Mediterranean dietary patterns should be considered as primary nutritional recommendation for cardiovascular disease prevention among individuals with diabetes.

http://ift.tt/2gEazaY

Behavioral and neurophysiological mechanisms underlying motor skill learning in patients with post-stroke hemiparesis

Skilled actions of daily life such as reaching across a busy table to pick a coffee mug are often performed with accurate, yet fast and efficient arm movements. Such complex skilled actions require optimization of speed and accuracy; and rely on efficient planning and execution (Begliomini et al., 2014; Fang et al., 2015; Orban de Xivry et al., 2017; Stewart et al., 2013). Following a neurological insult such as stroke, skilled arm movements are greatly impaired in the paretic (weaker) arm such that task performance is slow, inaccurate and fragmented (Cirstea et al., 2003; Levin, 1996; Liu et al., 2013; Shaikh et al., 2014; Silva et al., 2014).

http://ift.tt/2y5EzHW

Copanlisib Produces Prolonged Responses in Lymphoma [News in Brief]

More than half of patients respond to the PI3K inhibitor, which may be safer than idelalisib.

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Inter-individual variability in muscle sympathetic responses to static handgrip in young men: Evidence for sympathetic responder types?

Negative and positive muscle sympathetic nerve activity (MSNA) responders have been observed during mental stress. We hypothesized that similar MSNA response patterns could be identified during the first minute of static handgrip and contribute to the inter-individual variability throughout exercise. Supine measurements of multi-unit MSNA (microneurography) and continuous blood pressure (Finometer) were recorded in 29 young healthy men during the first (HG1) and second (HG2) minute of static handgrip (30% maximal voluntary contraction) and subsequent post-exercise circulatory occlusion (PECO). Responders were identified based on differences from the typical error of baseline total MSNA; 7 negative, 12 positive, and 10 non-response patterns. Positive responders demonstrated larger total MSNA responses during HG1 (p<0.01) and HG2 (p<0.0001), however, the increases in blood pressure throughout handgrip exercise were similar between all groups, as were the changes in heart rate, stroke volume, cardiac output, total vascular conductance, and respiration (All p>0.05). Comparing negative and positive responders, total MSNA responses were similar during PECO (p=0.17) but opposite from HG2 to PECO (40±46 vs. -21±62%, p=0.04). Negative responders also had a shorter time-to-peak diastolic blood pressure during HG1 (20±20 vs. 44±14 seconds, p<0.001). Total MSNA responses during HG1 were associated with responses to PECO (r=0.39, p<0.05), the change from HG2 to PECO (r=-0.49, p<0.01), and diastolic blood pressure time-to-peak (r=0.50, p<0.01). Overall, MSNA response patterns during the first minute of static handgrip contribute to inter-individual variability, and appear to be influenced by differences in central command, muscle metaboreflex activation, and rate of loading of the arterial baroreflex.

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Aerobic exercise training-induced changes in serum C1q/TNF-related protein levels are associated with reduced arterial stiffness in middle-aged and older adults

Adiponectin regulates endothelial nitric oxide synthase in endothelial cells, and body fat loss by aerobic exercise training promotes adiponectin secretion. Recently, C1q/tumor necrosis factor-related proteins (CTRPs) have been identified as novel adipokines and are paralogs of adiponectin, but the association between exercise training-induced reduction of arterial stiffness and circulating CTRPs levels remains unclear. This study aimed to clarify whether the reduction of arterial stiffness in middle-aged and older adults is associated with the change in serum levels of CTRPs induced by exercise training. A total of 52 middle-aged and older participants were randomly divided into two groups: the training group (n=26) and the sedentary control group (n=26). Participants in the training group completed 8 weeks of aerobic exercise training (60-70% peak oxygen uptake for 45min, 3days/week). The reduction of % whole body fat, abdominal visceral fat area, and carotid-femoral pulse wave velocity (cfPWV) was significantly greater in the training group than in the control group (P<0.05). Moreover, the increase in serum adiponectin, CTRP3, and CTRP5 from baseline to 8-week was significantly higher in the training group compared to the control group (P<0.05). Additionally, the training-induced change in cfPWV was negatively correlated with the training-induced change in serum adiponectin, CTRP3, and CTRP5 levels (r=–0.51, r=–0.48, r=–0.42, respectively, P<0.05), and increased plasma nitrite/nitrate level by exercise training was only correlated with adiponectin levels (r=0.41, P<0.05). These results suggest that the exercise training-induced increase in serum CTRPs levels may be associated with the reduction of arterial stiffness in middle-aged and older adults.

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The 2017 New Investigator Review Awards

n/a

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Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) link vitamin B6 catabolism and lung cancer risk

Circulating pyridoxal-5'-phosphate (PLP) has been linked to lung cancer risk. The PAr index, defined as the ratio 4-pyridoxic acid / (pyridoxal + PLP), reflects increased vitamin B6 catabolism during inflammation. PAr has been defined as a marker of lung cancer risk in a prospective cohort study, but analysis of a larger numbers of cases are needed to deepen the significance of this study. Here we conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC, n = 521,330), which included 892 incident lung cancer cases and 1748 controls matched by center, gender, date of blood collection and date of birth. The association of PAr with risk of lung cancer was evaluated by using conditional logistic regression. Study participants with elevated PAr experienced higher risk of lung cancer in a dose-response fashion, with a doubling in PAr levels associated with 52% higher odds of lung cancer after adjustment for tobacco smoking, serum cotinine levels, educational attainment, and BMI (OR=1.52, 95% CI=1.27 to 1.81, P < 0.001). Additional adjustment for intake of vegetables and fruits and physical activity did not materially affect risk association. The association of PAr with lung cancer risk was similar in both genders but slightly stronger in former smokers and in participants diagnosed with squamous cell carcinoma. This study provides robust evidence that increased vitamin B6 catabolism is independently associated with a higher risk of future lung cancer.

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Mitochondrial haplotype alters mammary cancer tumorigenicity and metastasis in an oncogenic driver- dependent manner

Using a novel mouse model, a mitochondrial nuclear exchange model termed MNX, we tested the hypothesis that inherited mitochondrial haplotypes alter primary tumor latency and metastatic efficiency. Male FVB/N-Tg(MMTVneu)202Mul/J (Her2) transgenic mice were bred to female MNX mice having FVB/NJ nuclear DNA and either FVB/NJ, C57BL/6J or BALB/cJ mtDNA. Pups receiving the C57BL/6J or BALB/cJ mitochondrial genome (i.e. females crossed with Her2 males) showed significantly (p<0.001) longer tumor latency (262 v 293 v 225 days), fewer pulmonary metastases (5 v 7 v 15) and differences in size of lung metastases (1.2 v 1.4 v 1.0 mm diameter) compared to FVB/NJ mtDNA. Although PyMT-driven tumors showed altered primary and metastatic profiles in previous studies, depending upon nuclear and mtDNA haplotype, the magnitude and direction of changes were not the same in the HER2-driven mammary carcinomas. Collectively, these results establish mitochondrial polymorphisms as quantitative trait loci in mammary carcinogenesis, and they implicate distinct interactions between tumor drivers and mitochondria as critical modifiers of tumorigenicity and metastasis.

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Type I IFN receptor signalling controls IL-7-dependent accumulation and activity of protumoral IL-17A-producing {gamma}{delta}T cells in breast cancer

The protumoral activity of γδT17 cells has recently emerged in a wide variety of solid malignancies including breast cancer. These cells promote tumor growth, angiogenesis, and subsequent metastasis development. However, the factors that regulate the biology of γδT17 cells within the tumor microenvironment are poorly understood. Here we use two experimental models of breast cancer to reinforce the concept that tumor-infiltrating γδT17 cells are endowed with protumoral functions that promote tumor progression and metastasis development. We also demonstrated a critical role for type I interferon signaling in controlling the preferential accumulation of a peculiar subset of γδT17 cells displaying a CD27- CD3bright phenotype in the tumor bed, previously associated with the invariant Vγ6Vδ1+ TCR. This effect was indirect and relied partially on IFNAR1-dependent control of IL-7 secretion, a factor that triggers proliferation and activating functions of deleterious γδT17 cells. Our work identifies a key role of the type I interferon/IL-7 axis in the regulation of intratumoral γδT17 cell functions and in the development of primary breast tumor growth and metastasis.

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The Instrument for Measuring the Implementation Situation of Traditional Chinese Medicine Guideline: Evaluation and Application

Clinical practice guidelines play an important role in reducing the variations in clinical practices and improving the quality of care. To assess the real effect, measuring its implementation situation is needed. The implementation situation can be reflected by testing the consistency between the actual clinical practice and the guideline. We constructed an instrument to measure the implementation situation of Traditional Chinese Medicine (TCM) guideline through consistency testing. The main objectives of our study were to validate the instrument and evaluate the implementation situation of menopause syndrome guideline of TCM, using the data from the consistency test of comparing the medical records with the guideline. A total of 621 cases were included for data analysis. Cronbach's Alpha coefficient is 0.73. The model fit of 7 items in four dimensions was good (SRMR = 0.04; GFI = 0.97; NFI = 0.97; TLI = 0.96; CFI = 0.98; AGFI = 0.90). This instrument is of good reliability and validity. It can help the guideline developers to measure the implementation situation, find the reasons affecting the implementation, and revise the guideline. The method of using consistency test to measure the implementation situation may provide a sample for evaluating the guideline implementation in other fields.

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Outcome of Critically Ill Patients with Testicular Cancer

Purpose. To evaluate the clinical characteristics and outcomes of critically ill patients with testicular cancer (TC) admitted to an oncological intensive care unit (ICU). Methods. This was a prospective observational study. There were no interventions. Results. During the study period, 1,402 patients with TC were admitted to the Department of Oncology, and 60 patients (4.3%) were admitted to the ICU. The most common histologic type was nonseminomatous germ cell tumors (55/91.7%). The ICU, hospital, and 6-month mortality rates were 38.3%, 45%, and 63.3%, respectively. The Cox multivariate analysis identified the white blood cells count (HR = 1.06, 95% CI = 1.01–1.11, and ), ionized calcium (iCa) level (HR = 1.23, 95% CI = 1.01–1.50, and ), and 2 or more organ failures during the first 24 hours after ICU admission (HR = 3.86, 95% CI = 1.96–7.59, and ) as independent predictors of death for up to 6 months. Conclusion. The ICU, hospital, and 6-month mortality rates were 38.3%, 45%, and 63.3%, respectively. The factors associated with an increased 6-month mortality rate were white blood cells count, iCa level, and 2 or more organ failures during the first 24 hours after ICU admission.

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Extracellular vesicles released by cardiomyocytes in a doxorubicin-induced cardiac injury mouse model contain protein biomarkers of early cardiac injury

Purpose: Cardiac injury is a major cause of death in cancer survivors, and biomarkers for it are detectable only after tissue injury has occurred. Extracellular vesicles (EVs) remove toxic biomolecules from tissues and can be detected in the blood. Here, we evaluate the potential of using circulating EVs as early diagnostic markers for long-term cardiac injury. Experimental Design: Using a mouse model of doxorubicin (DOX)-induced cardiac injury, we quantified serum EVs, analyzed proteomes, measured oxidized protein levels in serum EVs released after DOX treatment, and investigated the alteration of EV content. Results: Treatment with DOX caused a significant increase in circulating EVs (DOX_EVs) compared to saline-treated controls. DOX_EVs exhibited a higher level of 4-hydroxynonenal adducted proteins, a lipid peroxidation product linked to DOX-induced cardiotoxicity. Proteomic profiling of DOX_EVs revealed the distinctive presence of brain/heart, muscle, and liver isoforms of glycogen phosphorylase (GP), and their origins were verified to be heart, skeletal muscle, and liver, respectively. The presence of brain/heart GP (PYGB) in DOX_EVs correlated with a reduction of PYGB in heart, but not brain tissues. Manganese superoxide dismutase (MnSOD) overexpression, as well as pretreatment with cardioprotective agents and MnSOD mimetics, resulted in a reduction of EV-associated PYGB in mice treated with DOX. Kinetic studies indicated that EVs containing PYGB were released prior to the rise of cardiac troponin in the blood after DOX treatment, suggesting that PYGB is an early indicator of cardiac injury. Conclusions: EVs containing PYGB are an early and sensitive biomarker of cardiac injury.

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PTEN is fundamental for elimination of leukemia stem cells mediated by GSK126 targeting EZH2 in chronic myelogenous leukemia

Purpose:Leukemia stem cells (LSCs) are important source of tyrosine kinase inhibitor (TKI) resistance and disease relapse in chronic myelogenous leukemia (CML). Targeting LSCs may be an attractive strategy to override this thorny problem. Given that EZH2 was overexpressed in primary CML CD34+ cells, our purpose in this study was to evaluate the effects of targeting EZH2 on CML LSCs and clarify its underlying mechanism. Experimental Design：Human primary CML CD34+ cells and retrovirally-BCR-ABL-driven CML mouse model were employed to evaluate the effects of suppression of EZH2 by GSK126 or EZH2 specific shRNA in vitro and in vivo. Recruitment of EZH2 and H3K27me3 on the promoter of tumor suppressor gene PTEN in CML cells was measured by chromatin immunoprecipitation (ChIP) assay. Results: Our results showed that pharmacological inhibition of EZH2 by GSK126 not only elicited apoptosis and restricted cell growth in CML bulk leukemia cells, but also decreased LSCs in CML CD34+ cells while sparing those from normal bone marrow (NBM) CD34+ cells. Suppression of EZH2 by GSK126 or specific shRNA prolonged survival of CML mice and reduced the number of LSCs in mice. EZH2 knockdown resulted in elevation of PTEN and led to impaired recruitment of EZH2 and H3K27me3 on the promoter of PTEN gene. The effect of EZH2 knockdown in the CML mice was at least partially reversed by PTEN knockdown. Conclusions: These findings improve the understanding of the epigenetic regulation of stemness in CML LSCs, and warrants clinical trial of GSK126 in refractory patients with CML.

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Circulating Tumors Cells from Different Vascular Sites Exhibit Spatial Heterogeneity in Epithelial and Mesenchymal Composition and Distinct Clinical Significance in Hepatocellular Carcinoma

Purpose: The spatial heterogeneity of phenotypic and molecular characteristics of CTCs within circulatory system remains unclear. Herein, we mapped the distribution and characterized biological features of CTCs along the transportation route in hepatocellular carcinoma (HCC).  Experimental Design: In 73 localized HCC patients, blood was drawn from peripheral vein (PV), peripheral artery (PA), hepatic veins (HV), infrahepatic inferior vena cava (IHIVC) and portal vein (PoV) before tumor resection. Epithelial and mesenchymal transition (EMT) phenotype in CTCs were analyzed by a 4-channel immunofluorescence CellSearch assay and microfluidic quantitative RT-PCR. The clinical significance of CTCs from different vascular sites was evaluated. Results: The CTC number and size gradient between tumor efferent vessels and post-pulmonary peripheral vessels was marked. Tracking the fate of CTC clusters revealed that CTCs displayed an aggregated-singular-aggregated manner of spreading. Single-cell characterization demonstrated that EMT status of CTCs was heterogeneous across different vascular compartments. CTCs were predominantly epithelial at release, but switched to EMT-activated phenotype during hematogeneous transit via Smad2 and β-catenin signaling pathways. EMT activation in primary tumor correlated with total CTC number at HV, rather than epithelial or EMT-activated subsets of CTCs. Follow-up analysis suggested that CTC and circulating tumor microemboli burden in hepatic veins and peripheral circulation prognosticated postoperative lung metastasis and intrahepatic recurrence, respectively. Conclusions: The current data suggested that a profound spatial heterogeneity in cellular distribution and biological features existed among CTCs during circulation. Multi-vascular measurement of CTCs could help to reveal novel mechanisms of metastasis and facilitate prediction of postoperative relapse pattern in HCC.

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Thermal Acclimation Ability Varies in Temperate and Tropical Aquatic Insects from Different Elevations

Synopsis

It has long been recognized that populations and species occupying different environments vary in their thermal tolerance traits. However, far less attention has been given to the impact of different environments on the capacity for plastic adjustments in thermal sensitivity, i.e., acclimation ability. One hypothesis is that environments characterized by greater thermal variability and seasonality should favor the evolution of increased acclimation ability compared with environments that are aseasonal or thermally stable. Additionally, organisms under selection for high heat tolerance may experience a trade-off and lose acclimation ability. Few studies have tested these non-mutually exclusive hypotheses at both broad latitudinal and local elevation scales in phylogenetically paired taxa. Here, we measure short-term acclimation ability of the critical thermal maximum (CT_MAX) in closely related temperate and tropical mayflies (Ephemeroptera) and stoneflies (Plecoptera) from mountain streams at different elevations. We found that stream temperature was a good predictor of acclimation ability in mayflies, but not in stoneflies. Specifically, tropical mayflies showed reduced acclimation ability compared with their temperate counterparts. High elevation tropical mayflies had greater acclimation ability than low elevation mayflies, which reflected the wider temperature variation experienced in high elevation streams. In contrast, temperate and tropical stoneflies exhibited similar acclimation responses. We found no evidence for a trade-off between heat tolerance and acclimation ability in either taxonomic order. The acclimation response in stoneflies may reflect their temperate origin or foraging mode. In combination with previous studies showing tropical taxa have narrower thermal breadths, these results demonstrate that many lower elevation tropical aquatic insects are more vulnerable to climate warming than their temperate relatives.

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Shared Decision Making among Children with Medical Complexity: Results from a Population-Based Survey

To compare the rates of shared decision making (SDM) reported by parents of children with medical complexity (CMC) with the rates of SDM reported by parents of noncomplex children with special health care needs (CSHCN).

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The influence of stage at diagnosis and molecular subtype on breast cancer patient survival: a hospital-based multi-center study

Stage at diagnosis and molecular subtype are important clinical factors associated with breast cancer patient survival. However, subgroup survival data from a large study sample are limited in China. To estima...

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Thrombotic Microangiopathies (TTP, HUS, HELLP)

Thrombocytopenia, strictly defined as a platelet count less than 150,000, is common in the emergency department. Recognition, diagnostic investigation, and proper disposition of a thrombocytopenic patient are imperative. One group of disorders leading to thrombocytopenia is the thrombotic microangiopathies, hallmarked by platelet destruction. These thrombotic microangiopathies include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and hemolysis, elevated liver enzyme levels, low platelet count (HELLP), which should be distinguished from similar disease processes such as immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC) and heparin induced thrombocytopenia (HIT). In this article, clinical presentations, pathophysiology, diagnostic workup, management plans, complications, and dispositions are addressed for this complex group of platelet disorders.

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Contents

John C. Perkins and Jonathan E. Davis

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Contributors

GEORGE P. CANELLOS, MD

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Anemia

Patients with anemia are frequently encountered in the emergency department (ED); emergency physicians (EPs) often play an important role in the evaluation and management of anemia. Although many patients have findings consistent with anemia on routine laboratory tests, only a small percentage will require acute intervention. An understanding of the broader types of anemia and how to manage such patients is important in the practice of an EP, as the presence of anemia will impact treatment plans for a variety of other disorders. This article reviews the evaluation and management of adult patients presenting to the ED with anemia.

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Neutropenic Fever

Fever is a common presenting complaint among adult or pediatric patients in the emergency department setting. Although fever in healthy individuals does not necessarily indicate severe illness, fever in patients with neutropenia may herald a life-threatening infection. Therefore, prompt recognition of patients with neutropenic fever is imperative. Serious bacterial illness is a significant cause of morbidity and mortality for neutropenic patients. Neutropenic fever should trigger the initiation of a rapid work-up and the administration of empiric systemic antibiotic therapy to attenuate or avoid the progression along the spectrum of sepsis, severe sepsis, septic shock syndrome, and death.

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Hematology/Oncology Emergencies

HEMATOLOGY/ONCOLOGY CLINICS OF NORTH AMERICA

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Forthcoming Issues

Castleman Disease

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Hematology/Oncology Emergencies

Hematologic and oncologic (heme/onc) emergencies are an ever-increasing occurrence in emergency departments (ED) around the world. Our population is aging; more patients are receiving chemotherapy and related treatments, and patients are living longer with chronic heme/onc comorbid conditions. And regardless of training background, many emergency providers (EP) still feel uncomfortable when faced with heme/onc emergencies. In this issue of the Hematology/Oncology Clinics of North America, we cover the most common heme/onc emergencies so that any EP will feel more comfortable with diagnosis, evaluation, and urgent or emergent treatments.

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Sickle Cell Disease in the Emergency Department

Acute painful episodes are the most common reason for emergency department visits among patients with sickle cell disease (SCD). Early and aggressive pain management is a priority. Emergency providers (EPs) must also diagnose other emergent diagnoses in patients with SCD and differentiate them from vaso-occlusive crisis. EPs should be aware of cognitive biases that may misdirect the diagnostic process. Administration of intravenous fluids should be used judiciously. Blood transfusion may be considered. Coordination of care with hematology is an important part of the effective emergency department and long-term management of patients with SCD.

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Myeloproliferative Disorders

The emergency providers generally encounters myeloproliferative disorders (MPNs) in 1 of 2 ways: as striking laboratory abnormalities of seeming unknown consequence, or in previously diagnosed patients presenting with complications. The course of patients with MPNs is highly variable, but major complications can arise. Emergent conditions related to hyperviscosity need to be recognized early and treated aggressively. Rapid hydration, transfusion, cytoreduction, and early hematology consultation can be lifesaving. Likewise, although management is not altered, a high index of suspicion for thrombotic complications is required in patients with known MPNs as these are a significant cause of morbidity and mortality.

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Antithrombotic Reversal Agents

The actively bleeding anticoagulated patient presenting to the emergency department requires rapid evaluation and treatment, which is made increasingly complicated by the ever-evolving antithrombotic treatment options used in medicine. Even with excellent supportive care, the timeliness with which reversal decisions need to be made continues to demand of the emergency practitioner a familiarity with the properties and general characteristics of a variety of antithrombotic agents. Reversal options vary and may include vitamin K, FFP, PCC, rFVIIa, platelets, and desmopressin, among others.

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Chemotherapeutic Medications and Their Emergent Complications

Patients with complications of chemotherapy, either acute or chronic, are frequently encountered in the emergency department (ED). Some patients present with complaints immediately after chemotherapy administration, whereas others may show subtle, secondary signs or may have no signs or symptoms of chemotoxicity. An increased index of suspicion prompts early recognition, diagnosis, and prevention of further iatrogenic injury. This article reviews characteristic hypersensitivity reactions, typical organ system dysfunction, and treatment strategies for adult patients who present to the ED with complications after chemotherapy.

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Acquired Bleeding Disorders

Emergency medicine practitioners treat bleeding patients on a regular basis. Disorders of hemostasis are an additional challenge in these patients but can be assessed and managed in a systematic fashion. Of particular importance to the emergency clinician are the iatrogenic causes of abnormal hemostasis. Other acquired causes of abnormal hemostasis include renal disease, immune thrombocytopenia, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, acquired coagulation factor inhibitors, acute traumatic coagulopathy, liver disease, and disseminated intravascular coagulopathy.

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Pediatric Oncologic Emergencies

The overall prognosis for most pediatric cancers is good. Mortality for all childhood cancers combined is approximately half what it was in 1975, and the survival rates of many malignancies continue to improve. However, the incidence of childhood cancer is significant and the related emergencies that develop acutely carry significant morbidity and mortality. Emergency providers who can identify and manage oncologic emergencies can contribute significantly to an improved prognosis. Effective care of pediatric malignancies requires an age-appropriate approach to patients and compassionate understanding of family dynamics.

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Oncologic Mechanical Emergencies

Prevalence of cancer and its various related complications continues to rise. Increasingly these life-threatening complications are initially managed in the emergency department, making a prompt and accurate diagnosis crucial to effectively institute the proper treatment and establish goals of care. The following oncologic emergencies are reviewed in this article: pericardial tamponade, superior vena cava syndrome, brain metastasis, malignant spinal cord compression, and hyperviscosity syndrome.

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Time is running short for a chance to "Choose Your Tools" from California Casualty

SAN MATEO, Calif. — It's the last chance to enter California Casualty's latest Work Hard/Play Hard Sweepstakes. One lucky first responder will receive their pick of $5,000 worth of DeWALT®* guaranteed tough tools. The deadline for entries is November 13 at http://ift.tt/2y4c517. The contest is open to peace officers, EMTs and firefighters; American heroes who work hard and ...

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Prevalence and determinants of burnout syndrome among physicians in Cameroon: a research proposal

Burnout syndrome is a common psychological state, that may affect human healthcare providers due to their prolonged exposure to job stressors. Burnout can hinder optimal healthcare delivery. Hence this study a...

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Adherence to iron supplements among women receiving antenatal care at Mulago National Referral Hospital, Uganda-cross-sectional study

Antenatal iron supplementation is a cost effective way of reducing iron deficiency anaemia among pregnant women in resource limited countries like Uganda. Poor adherence to iron supplements has limited its eff...

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Potential of Lanistes varicus in limiting the population of Bulinus truncatus

To determine the ability of the Ampullariid, Lanistes varicus to prey on egg masses and juveniles of Bulinus truncatus snails, an intermediate host of urogenital schistosomiasis in West Africa.

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Why paramedics do not run to treat patients

A user on Quora recently asked, "Why don't paramedics run to emergency patients"" A few answers stood out to us, especially one by EMT Ross Cohen. You can read his reply below: I'm glad you asked, because I promise you it's not due to a lack of concern. It's actually perfectly logical when you see it from our point of view. 3 Main Reasons: Running is risky. If we trip ...

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With FDA Approval for Advanced Lymphoma, Second CAR T-Cell Therapy Moves to the Clinic

One month after approving the first CAR T-cell therapy for cancer, FDA has approved a second such therapy. The treatment, axicabtagene ciloleucel (Yescarta™), was approved for some patients with advanced non-Hodgkin lymphoma.

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Risk stratification using SpO2/FiO2 and PEEP at initial ARDS diagnosis and after 24 h in patients with moderate or severe ARDS

We assessed the potential of risk stratification of ARDS patients using SpO2/FiO2 and positive end-expiratory pressure (PEEP) at ARDS onset and after 24 h.

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Isolation of Salmonella typhimurium-containing Phagosomes from Macrophages

We describe here a simple and quick method for the isolation of Salmonella typhimurium-containing phagosomes from macrophages by coating the bacteria with biotin and streptavidin.

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DNA Nanotubes as a Versatile Tool to Study Semiflexible Polymers

Semiflexible polymers display unique mechanical properties that are extensively applied by living systems. However, systematic studies on biopolymers are limited since properties such as polymer rigidity are inaccessible. This manuscript describes how this limitation is circumvented by programmable DNA nanotubes, enabling experimental studies on the impact of filament rigidity.

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Ala. schools adopt 911 app to shorten response times

A staff member who is faced with an emergency can select from active shooter, fire, police, medical or 911, and a dispatcher will direct their call

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Operation of a 25 KWth Calcium Looping Pilot-plant with High Oxygen Concentrations in the Calciner

This manuscript describes a procedure for operating a calcium looping pilot-plant for post-combustion carbon capture with high oxygen concentrations in the calciner in order to reduce or eliminate the flue gas recycle.

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University to design ‘super ambulance’ to speed up cardiac arrest treatment

The University of Minnesota is researching how they can equip ambulances with the latest imaging and heart-lung bypass technology

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Comparison of Zinc Finger Nucleases Versus CRISPR-Specific Nucleases for Genome Editing of the Wiskott-Aldrich Syndrome Locus

Human Gene Therapy , Vol. 0, No. 0.


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Modeling Amyloid-β42 Toxicity and Neurodegeneration in Adult Zebrafish Brain

This protocol describes the synthesis, characterization, and injection of monomeric amyloid-β42 peptides for generating amyloid toxicity in adult zebrafish to establish an Alzheimer's disease model, followed by histological analyses and detection of aggregations.

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The Changing Face of Surgical Oncology

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The Role of Intersphincteric Resection in Very Low Rectal Cancer

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Reply to: Partial Verification Distorts Estimates of Sensitivity in Diagnostic Accuracy Studies for Fine-Needle Aspiration Cytology

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Impact of RAS Mutations in Metastatic Colorectal Cancer After Potentially Curative Resection: Does Site of Metastases Matter?

Abstract

Background

RAS mutation status is an important prognostic factor after resection of liver metastases (LiM) from colorectal cancer (CRC). The prognostic significance of RAS after resection of lung (LuM) and peritoneal (PM) metastases from CRC is unknown.

Methods

Between 2005 and 2014, all consecutive patients with known RAS status who underwent potentially curative resection for LiM, LuM, or PM were evaluated.

Results

A total of 720 patients with known RAS status underwent resection of LiM (n = 468), LuM (n = 102), and PM (n = 150). RAS mutations were identified in 63 and 58% of patients with LuM and PM, respectively, compared with 41% of patients with LiM (p < 0.001). Five-year overall survival (OS) after resection of PM was 45%, compared with 52% after resection of LiM (p = 0.018) and 64% after resection of LuM (p = 0.005). RAS mutations were associated with significantly worse OS after resection of LiM (p < 0.001), but did not affect OS among patients undergoing resection of LuM (p = 0.41) and PM (p = 0.65).

Conclusions

RAS mutations are more prevalent among patients undergoing resection of LuM and PM than LiM but do not affect survival after lung and peritoneal metastasectomy, as they do after hepatectomy. These results suggest that the prognostic significance of RAS mutations after resection of metastatic CRC depends on the specific site of metastases.

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Vitamin D Levels Affect Breast Cancer Survival Rates: A Reply

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Signatures of Somatic Inhibition and Dendritic Excitation in Auditory Brainstem Field Potentials

Extracellular voltage recordings (V_e; field potentials) provide an accessible view of in vivo neural activity, but proper interpretation of field potentials is a long-standing challenge. Computational modeling can aid in identifying neural generators of field potentials. In the auditory brainstem of cats, spatial patterns of sound-evoked V_e can resemble, strikingly, V_e generated by current dipoles. Previously, we developed a biophysically-based model of a binaural brainstem nucleus, the medial superior olive (MSO), that accounts qualitatively for observed dipole-like V_e patterns in sustained responses to monaural tones with frequencies >~1000 Hz (Goldwyn et al., 2014). We have observed, however, that V_e patterns in cats of both sexes appear more monopole-like for lower-frequency tones. Here, we enhance our theory to accurately reproduce dipole and non-dipole features of V_e responses to monaural tones with frequencies ranging from 600 to 1800 Hz. By applying our model to data, we estimate time courses of paired input currents to MSO neurons. We interpret these inputs as dendrite-targeting excitation and soma-targeting inhibition (the latter contributes non-dipole-like features to V_e responses). Aspects of inferred inputs are consistent with synaptic inputs to MSO neurons including the tendencies of inhibitory inputs to attenuate in response to high-frequency tones and to precede excitatory inputs. Importantly, our updated theory can be tested experimentally by blocking synaptic inputs. MSO neurons perform a critical role in sound localization and binaural hearing. By solving an inverse problem to uncover synaptic inputs from V_e patterns we provide a new perspective on MSO physiology.

SIGNIFICANCE STATEMENT Extracellular voltages (field potentials) are a common measure of brain activity. Ideally, one could infer from these data the activity of neurons and synapses that generate field potentials, but this "inverse problem" is not easily solved. We study brainstem field potentials in the region of the medial superior olive (MSO); a critical center in the auditory pathway. These field potentials exhibit distinctive spatial and temporal patterns in response to pure tone sounds. We use mathematical modeling in combination with physiological and anatomical knowledge of MSO neurons to plausibly explain how dendrite-targeting excitation and soma-targeting inhibition generate these field potentials. Inferring putative synaptic currents from field potentials advances our ability to study neural processing of sound in the MSO.

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The Timing of Reward-Seeking Action Tracks Visually Cued Theta Oscillations in Primary Visual Cortex

An emerging body of work challenges the view that primary visual cortex (V1) represents the visual world faithfully. Theta oscillations in the local field potential (LFP) of V1 have been found to convey temporal expectations and, specifically, to express the delay between a visual stimulus and the reward that it portends. We extend this work by showing how these oscillatory states in male, wild-type rats can even relate to the timing of a visually cued reward-seeking behavior. In particular, we show that, with training, high precision and accuracy in behavioral timing tracks the power of these oscillations and the time of action execution covaries with their duration. These LFP oscillations are also intimately related to spiking responses at the single-unit level, which themselves carry predictive timing information. Together, these observations extend our understanding of the role of cortical oscillations in timing generally and the role of V1 in the timing of visually cued behaviors specifically.

SIGNIFICANCE STATEMENT Traditionally, primary visual cortex (V1) has been regarded as playing a purely perceptual role in stimulus-driven behaviors. Recent work has challenged that view by showing that theta oscillations in rodent V1 may come to convey timed expectations. Here, we show that these theta oscillations carry predictive information about timed reward-seeking actions, thus elucidating a behavioral role for theta oscillations in V1 and extending our understanding of the role of V1 in decision making.

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MEG Insight into the Spectral Dynamics Underlying Steady Isometric Muscle Contraction

To gain fundamental knowledge on how the brain controls motor actions, we studied in detail the interplay between MEG signals from the primary sensorimotor (SM1) cortex and the contraction force of 17 healthy adult humans (7 females, 10 males). SM1 activity was coherent at ~20 Hz with surface electromyogram (as already extensively reported) but also with contraction force. In both cases, the effective coupling was dominant in the efferent direction. Across subjects, the level of ~20 Hz coherence between cortex and periphery positively correlated with the "burstiness" of ~20 Hz SM1 (Pearson r 0.65) and peripheral fluctuations (r 0.9). Thus, ~20 Hz coherence between cortex and periphery is tightly linked to the presence of ~20 Hz bursts in SM1 and peripheral activity. However, the very high correlation with peripheral fluctuations suggests that the periphery is the limiting factor. At frequencies <3 Hz, both SM1 signals and ~20 Hz SM1 envelope were coherent with both force and its absolute change rate. The effective coupling dominated in the efferent direction between (1) force and the ~20 Hz SM1 envelope and (2) the absolute change rate of the force and SM1 signals. Together, our data favor the view that ~20 Hz coherence between cortex and periphery during isometric contraction builds on the presence of ~20 Hz SM1 oscillations and needs not rely on feedback from the periphery. They also suggest that effective cortical proprioceptive processing operates at <3 Hz frequencies, even during steady isometric contractions.

SIGNIFICANCE STATEMENT Accurate motor actions are made possible by continuous communication between the cortex and spinal motoneurons, but the neurophysiological basis of this communication is poorly understood. Using MEG recordings in humans maintaining steady isometric muscle contractions, we found evidence that the cortex sends population-level motor commands that tend to structure according to the ~20 Hz sensorimotor rhythm, and that it dynamically adapts these commands based on the <3 Hz fluctuations of proprioceptive feedback. To our knowledge, this is the first report to give a comprehensive account of how the human brain dynamically handles the flow of proprioceptive information and converts it into appropriate motor command to keep the contraction force steady.

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Spatial Structure of Synchronized Inhibition in the Olfactory Bulb

Olfactory sensory input is detected by receptor neurons in the nose, which then send information to the olfactory bulb (OB), the first brain region for processing olfactory information. Within the OB, many local circuit interneurons, including axonless granule cells, function to facilitate fine odor discrimination. How interneurons interact with principal cells to affect bulbar processing is not known, but the mechanism is likely to be different from that in sensory cortical regions because the OB lacks an obvious topographical organization. Neighboring glomerular columns, representing inputs from different receptor neuron subtypes, typically have different odor tuning. Determining the spatial scale over which interneurons such as granule cells can affect principal cells is a critical step toward understanding how the OB operates. We addressed this question by assaying inhibitory synchrony using intracellular recordings from pairs of principal cells with different intersomatic spacing. We found, in acute rat OB slices from both sexes, that inhibitory synchrony is evident in the spontaneous synaptic input in mitral cells (MCs) separated up to 220 μm (300 μm with elevated K⁺). At all intersomatic spacing assayed, inhibitory synchrony was dependent on Na⁺ channels, suggesting that action potentials in granule cells function to coordinate GABA release at relatively distant dendrodendritic synapses formed throughout the dendritic arbor. Our results suggest that individual granule cells are able to influence relatively large groups of MCs and tufted cells belonging to clusters of at least 15 glomerular modules, providing a potential mechanism to integrate signals reflecting a wide variety of odorants.

SIGNIFICANCE STATEMENT Inhibitory circuits in the olfactory bulb (OB) play a major role in odor processing, especially during fine odor discrimination. However, how inhibitory networks enhance olfactory function, and over what spatial scale they operate, is not known. Interneurons are potentially able to function on both a highly localized, synapse-specific level and on a larger, spatial scale that encompasses many different glomerular channels. Although recent indirect evidence has suggested a relatively localized functional role for most inhibition in the OB, in the present study, we used paired intracellular recordings to demonstrate directly that inhibitory local circuits operate over large spatial scales by using fast action potentials to link GABA release at many different synaptic contacts formed with principal cells.

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Weak Higher-Order Interactions in Macroscopic Functional Networks of the Resting Brain

Interactions among different brain regions are usually examined through functional connectivity (FC) analysis, which is exclusively based on measuring pairwise correlations in activities. However, interactions beyond the pairwise level, that is, higher-order interactions (HOIs), are vital in understanding the behavior of many complex systems. So far, whether HOIs exist among brain regions and how they can affect the brain's activities remains largely elusive. To address these issues, here, we analyzed blood oxygenation level-dependent (BOLD) signals recorded from six typical macroscopic functional networks of the brain in 100 human subjects (46 males and 54 females) during the resting state. Through examining the binarized BOLD signals, we found that HOIs within and across individual networks were both very weak regardless of the network size, topology, degree of spatial proximity, spatial scales, and whether the global signal was regressed. To investigate the potential mechanisms underlying the weak HOIs, we analyzed the dynamics of a network model and also found that HOIs were generally weak within a wide range of key parameters provided that the overall dynamic feature of the model was similar to the empirical data and it was operating close to a linear fluctuation regime. Our results suggest that weak HOI may be a general property of brain's macroscopic functional networks, which implies the dominance of pairwise interactions in shaping brain activities at such a scale and warrants the validity of widely used pairwise-based FC approaches.

SIGNIFICANCE STATEMENT To explain how activities of different brain areas are coordinated through interactions is essential to revealing the mechanisms underlying various brain functions. Traditionally, such an interaction structure is commonly studied using pairwise-based functional network analyses. It is unclear whether the interactions beyond the pairwise level (higher-order interactions or HOIs) play any role in this process. Here, we show that HOIs are generally weak in macroscopic brain networks. We also suggest a possible dynamical mechanism that may underlie this phenomenon. These results provide plausible explanation for the effectiveness of widely used pairwise-based approaches in analyzing brain networks. More importantly, it reveals a previously unknown, simple organization of the brain's macroscopic functional systems.

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The Intellectual Disability and Schizophrenia Associated Transcription Factor TCF4 Is Regulated by Neuronal Activity and Protein Kinase A

Transcription factor 4 (TCF4 also known as ITF2 or E2-2) is a basic helix-loop-helix (bHLH) protein associated with Pitt–Hopkins syndrome, intellectual disability, and schizophrenia (SCZ). Here, we show that TCF4-dependent transcription in cortical neurons cultured from embryonic rats of both sexes is induced by neuronal activity via soluble adenylyl cyclase and protein kinase A (PKA) signaling. PKA phosphorylates TCF4 directly and a PKA phosphorylation site in TCF4 is necessary for its transcriptional activity in cultured neurons and in the developing brain in vivo. We also demonstrate that Gadd45g (growth arrest and DNA damage inducible gamma) is a direct target of neuronal-activity-induced, TCF4-dependent transcriptional regulation and that TCF4 missense variations identified in SCZ patients alter the transcriptional activity of TCF4 in neurons. This study identifies a new role for TCF4 as a neuronal-activity-regulated transcription factor, offering a novel perspective on the association of TCF4 with cognitive disorders.

SIGNIFICANCE STATEMENT The importance of the basic helix-loop-helix transcription factor transcription factor 4 (TCF4) in the nervous system is underlined by its association with common and rare cognitive disorders. In the current study, we show that TCF4-controlled transcription in primary cortical neurons is induced by neuronal activity and protein kinase A. Our results support the hypotheses that dysregulation of neuronal-activity-dependent signaling plays a significant part in the etiology of neuropsychiatric and neurodevelopmental disorders.

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Chd7 Collaborates with Sox2 to Regulate Activation of Oligodendrocyte Precursor Cells after Spinal Cord Injury

Oligodendrocyte precursor cells (OPCs) act as a reservoir of new oligodendrocytes (OLs) in homeostatic and pathological conditions. OPCs are activated in response to injury to generate myelinating OLs, but the underlying mechanisms remain poorly understood. Here, we show that chromodomain helicase DNA binding protein 7 (Chd7) regulates OPC activation after spinal cord injury (SCI). Chd7 is expressed in OPCs in the adult spinal cord and its expression is upregulated with a concomitant increase in Sox2 expression after SCI. OPC-specific ablation of Chd7 in injured mice leads to reduced OPC proliferation, the loss of OPC identity, and impaired OPC differentiation. Ablation of Chd7 or Sox2 in cultured OPCs shows similar phenotypes to those observed in Chd7 knock-out mice. Chd7 and Sox2 form a complex in OPCs and bind to the promoters or enhancers of the regulator of cell cycle (Rgcc) and protein kinase C (PKC) genes, thereby inducing their expression. The expression of Rgcc and PKC is reduced in the OPCs of the injured Chd7 knock-out mice. In cultured OPCs, overexpression and knock-down of Rgcc or PKC promote and suppress OPC proliferation, respectively. Furthermore, overexpression of both Rgcc and PKC rescues the Chd7 deletion phenotypes. Chd7 is thus a key regulator of OPC activation, in which it cooperates with Sox2 and acts via direct induction of Rgcc and PKC expression.

SIGNIFICANCE STATEMENT Spinal cord injury (SCI) leads to oligodendrocyte (OL) loss and demyelination, along with neuronal death, resulting in impairment of motor or sensory functions. Oligodendrocyte precursor cells (OPCs) activated in response to injury are potential sources of OL replacement and are thought to contribute to remyelination and functional recovery after SCI. However, the molecular mechanisms underlying OPC activation, especially its epigenetic regulation, remain largely unclear. We demonstrate here that the chromatin remodeler chromodomain helicase DNA binding protein 7 (Chd7) regulates the proliferation and identity of OPCs after SCI. We have further identified regulator of cell cycle (Rgcc) and protein kinase C (PKC) as novel targets of Chd7 for OPC activation.

http://ift.tt/2gC4lrU

Extremely Vivid, Highly Transparent, and Ultrathin Quantum Dot Light-Emitting Diodes

Abstract

Displaying information on transparent screens offers new opportunities in next-generation electronics, such as augmented reality devices, smart surgical glasses, and smart windows. Outstanding luminance and transparency are essential for such "see-through" displays to show vivid images over clear background view. Here transparent quantum dot light-emitting diodes (Tr-QLEDs) are reported with high brightness (bottom: ≈43 000 cd m⁻², top: ≈30 000 cd m⁻², total: ≈73 000 cd m⁻² at 9 V), excellent transmittance (90% at 550 nm, 84% over visible range), and an ultrathin form factor (≈2.7 µm thickness). These superb characteristics are accomplished by novel electron transport layers (ETLs) and engineered quantum dots (QDs). The ETLs, ZnO nanoparticle assemblies with ultrathin alumina overlayers, dramatically enhance durability of active layers, and balance electron/hole injection into QDs, which prevents nonradiative recombination processes. In addition, the QD structure is further optimized to fully exploit the device architecture. The ultrathin nature of Tr-QLEDs allows their conformal integration on various shaped objects. Finally, the high resolution patterning of red, green, and blue Tr-QLEDs (513 pixels in.⁻¹) shows the potential of the full-color transparent display.

Extremely bright, transparent, and ultrathin quantum dot light-emitting diodes are achieved by engineering electron transport layer and quantum dots, which leads to the highest luminance (bottom: ≈43 000 cd m⁻², top: ≈30 000 cd m⁻² at 9 V) and transparency (90% at 550 nm) among all types of transparent displays. The ultrathin transparent quantum dot light-emitting diodes can also conformally be integrated on various curvilinear surfaces.

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In Situ Coupling Strategy for the Preparation of FeCo Alloys and Co4N Hybrid for Highly Efficient Oxygen Evolution

Abstract

An in situ coupling approach is developed to create a new highly efficient and durable cobalt-based electrocatalyst for the oxygen evolution reaction (OER). Using a novel cyclotetramerization, a task-specific bimetallic phthalocyanine-based nanoporous organic framework is successfully built as a precursor for the carbonization synthesis of a nonprecious OER electrocatalyst. The resultant material exhibits an excellent OER activity with a low overpotential of 280 mV at a current density of 10 mA cm⁻² and high durability in an alkaline medium. This impressive result ranks among the best from known Co-based OER catalysts under the same conditions. The simultaneous installation of multiple diverse cobalt-based active sites, including FeCo alloys and Co₄N nanoparticles, plays a critical role in achieving this promising OER performance. This innovative approach not only enables high-performance OER activity to be achieved but simultaneously provides a means to control the surface features, thereby tuning the catalytic property of the material.

A new highly efficient and durable cobalt-based oxygen evolution reaction (OER) electrocatalyst is developed by an in situ coupling approach. A bimetallic phthalocyanine-based framework is built for the construction of the desirable catalyst. The material exhibits an excellent OER activity with a low overpotential of 280 mV at 10 mA cm⁻² and high durability in an alkaline medium.

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Vertical Growth of 2D Amorphous FePO4 Nanosheet on Ni Foam: Outer and Inner Structural Design for Superior Water Splitting

Abstract

Rational design of highly efficient bifunctional electrocatalysts based on 3D transition-metal-based materials for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is of great importance for sustainable energy conversion processes. Herein, a novel strategy involving outer and inner structural engineering is developed for superior water splitting via in situ vertical growth of 2D amorphous FePO₄ nanosheets on Ni foam (Am FePO₄/NF). Careful experiments and density functional theory calculations show that the inner and outer structural engineering contributing to the synergistic effects of 2D morphology, amorphous structure, conductive substrate, and Ni−Fe mixed phosphate lead to superior electrocatalytic activity toward OER and HER. Furthermore, a two-electrode electrolyzer assembled using Am FePO₄/NF as an electrocatalyst at both electrodes gives current densities of 10 and 100 mA cm⁻² at potentials of 1.54 and 1.72 V, respectively, which is comparable to the best bifunctional electrocatalyst reported in the literature. The strategies, introduced in the present work, may open new opportunities for the rational design of other 3D transition-metal-based electrocatalyst through an outer and inner structural control to strengthen the electrocatalytic performance.

A novel strategy involving outer and inner structural engineering is developed for superior water splitting via in situ vertical growth of 2D amorphous nanosheets on Ni foam. This structural engineering contributing to the synergistic effect of 2D morphology, amorphous structure, and conductive substrate maps out a promising strategy for further improving catalytic activity of 3D transition-metal-based materials.

http://ift.tt/2y4nmhU

Prognostic value of change in anti-thyroglobulin antibodies after thyroidectomy in patients with papillary thyroid carcinoma

Abstract

Purpose

Anti-thyroglobulin antibodies (TgAb) can be used as a surrogate tumor marker in the follow-up of papillary thyroid carcinoma (PTC). We try to determine if the change in TgAb levels in the first post-operative year is a good predictor of persistence/recurrence risk in TgAb-positive PTC patients.

Methods/patients

105 patients with PTC who underwent thyroidectomy between 1988 and 2014 were enrolled. We calculated the percentage of change in TgAb levels with the first measurement at 1–2 months after surgery and the second one at 12–14 months.

Results

TgAb negativization was observed in 29 patients (27.6%), a decrease of more than 50% was observed in 57 patients (54.3%), less than 50% in 12 patients (11.4%) and in 7 patients (6.7%) the TgAb level had increased. The percentage of persistence/recurrence was 0, 8.8, 16.7 and 71.4% in each group, respectively (p < 0.001). In the multivariate analysis, only the percentage of change in TgAb showed a significant association with the risk of persistence/recurrence, regardless of other factors such as age, size and TNM stages.

Conclusions

Changes in TgAb levels in the first year after surgery can predict the risk of persistence/recurrence of TgAb-positive PTC patients. Patients who achieved negativization of TgAb presented an excellent prognosis.

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A non-randomized, open-label, single-arm, Phase 2 study of emibetuzumab in Asian patients with MET diagnostic positive, advanced gastric cancer

Abstract

Purpose

Mesenchymal–epithelial transition factor (MET) is expressed in gastric cancer and associated with poor clinical outcomes. We assessed activity, safety, and pharmacokinetics of emibetuzumab, a bivalent monoclonal anti-MET antibody that blocks ligand-dependent and ligand-independent MET signaling.

Methods

This non-randomized, single-arm, Phase 2 study enrolled Asian patients with MET diagnostic positive advanced gastric adenocarcinoma. Emibetuzumab (2000 mg, intravenous) was given on days 1 and 15 (28-day cycle). The primary endpoint was 8-week progression-free survival rate. Secondary objectives included safety, pharmacokinetics, overall survival, and change in tumor size.

Results

Tumors from 65 patients were immunohistochemically screened to enroll 15 MET diagnostic positive patients (23% positivity; 8 Japanese, 7 Korean; 10 male). Eight-week progression-free survival rate was 0.47 (70% CI, 0.33–0.59). Disease control rate was 40% (target lesion decreases, three patients; no complete/partial responses according to RECIST). Median overall survival was 17.1 weeks (95% CI, 6.3–not achievable). No serious emibetuzumab-related adverse events or new safety signals emerged. Grade ≥ 3 possibly drug-related adverse events were hyperkalemia, hyponatremia, and hyperuricemia (one each). Emibetuzumab's pharmacokinetics profile was similar to that observed previously. MET expression and clinical outcomes were not obviously associated.

Conclusion

Emibetuzumab was well tolerated with limited single-agent activity in advanced gastric adenocarcinoma.

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Scaffold-Based microRNA Therapies in Regenerative Medicine and Cancer

Abstract

microRNA-based therapies are an advantageous strategy with applications in both regenerative medicine (RM) and cancer treatments. microRNAs (miRNAs) are an evolutionary conserved class of small RNA molecules that modulate up to one third of the human nonprotein coding genome. Thus, synthetic miRNA activators and inhibitors hold immense potential to finely balance gene expression and reestablish tissue health. Ongoing industry-sponsored clinical trials inspire a new miRNA therapeutics era, but progress largely relies on the development of safe and efficient delivery systems. The emerging application of biomaterial scaffolds for this purpose offers spatiotemporal control and circumvents biological and mechanical barriers that impede successful miRNA delivery. The nascent research in scaffold-mediated miRNA therapies translates know-how learnt from studies in antitumoral and genetic disorders as well as work on plasmid (p)DNA/siRNA delivery to expand the miRNA therapies arena. In this progress report, the state of the art methods of regulating miRNAs are reviewed. Relevant miRNA delivery vectors and scaffold systems applied to-date for RM and cancer treatment applications are discussed, as well as the challenges involved in their design. Overall, this progress report demonstrates the opportunity that exists for the application of miRNA-activated scaffolds in the future of RM and cancer treatments.

MicroRNA-based therapies hold immense potential to finely balance gene expression and reestablish tissue health, but their progress largely relies on the development of safe and effective delivery systems. In this Progress Report future opportunities and current challenges that exist in the emerging application of biomaterial scaffolds as microRNA delivery platforms for regenerative medicine and cancer treatments are illustrated.

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Novel 1,3,5-Triazine Derivatives Exert Potent Anti-cervical Cancer Effects by Modulating Bax, Bcl2, and Caspases Expression

Abstract

The present study aimed to develop novel 1,3,5-triazine derivatives as potent anti-cervical cancer agents. The compounds were synthesised in short steps with an excellent yield and characterised via various spectroscopic and analytical methods. A structure–activity relationship study suggested that electron-withdrawing substituents showed greater anticancer activity than electron-donating groups. Compound 7p (p-fluoro) showed the highest activity against cervical cancer cells. In a nude mouse xenograft model inoculated with HeLa cells, 7p showed dose-dependent inhibition of cervical tumour growth. Histopathological examination of excised tumour-bearing tissues showed that 7p improved the microstructure in a dose-dependent manner. Compound 7p also increased the proportions of HeLa cells in G0/G1 and S-phase and significantly decreased that of G2/M-phase. The effects of 7p on C-caspase-3, C-caspase-9, Bcl-2, and Bax expression in HeLa cells were also determined.

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Structure–activity relationship study suggested that the halogen-containing compounds (F and Cl) had higher anticancer activity than non-halogen (OH, OCH₃, and CH₃) compounds.

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Structural Basis for the Agonist Action at Free Fatty Acid Receptor 1 (FFA1R or GPR40)

Abstract

G-protein-coupled receptor 40 (GPR40) was recently identified as an interesting target for treatment of type II diabetes. The high level of expression in pancreatic beta cells and the dependence of glucose on stimulating the secretion of insulin led to great excitement in this field. The identification of this target was followed by the development of a series of agonists with great potential for the treatment of diabetes. All known agonists have the presence of a pharmacophoric carboxylic acid group in their structure, which makes several polar interactions at the binding site of this receptor. In this report, we provide a review of the structure-activity relationships of GPR40 agonists with a focus on the main strategies of medicinal chemistry used to develop each one of the main structural patterns exploited for this purpose. Additionally, we provide a general model for the design of GPR40 ligands that can help researchers to follow up some strategies and implement them in the development of novel agonists of this receptor.

This article is protected by copyright. All rights reserved.

The high level of expression in pancreatic beta cells and the dependence of the glucose to stimulate the secretion of insulin make theGPR40 an interesting target for treatment of type II diabetes. The development of novel agonists of this receptor is a hot topic in Medicinal Chemistry. Herein, we describe a review on the structure-activity relationships of GPR40 agonists focusing on the main strategies of medicinal chemistry used to develop each one of the main structural patterns exploited for this purpose and we provide a general model for the design of novel GPR40 ligands.

http://ift.tt/2h8s5ET