Immunological hallmarks of cis -DDP-resistant Lewis lung carcinoma cells

Abstract

Purpose

Tumor cell resistance to platinum-based chemotherapeutic agents is one of the major hurdles to successful cancer treatment with these drugs, and is associated with alterations in tumor cell immune evasion and immunomodulatory properties. Immunocyte targeting is considered as a relevant approach to fight drug-resistant cancer. In this study, immunological hallmarks of cis-DDP-resistant Lewis lung carcinoma cells (LLC/R9) were investigated.

Methods

Immunological features of LLC/R9 cells cultured in vitro in normoxic and hypoxic conditions as well as of those that were grown in vivo were examined. The expression of immunologically relevant genes was evaluated by RT-PCR. Tumor cell susceptibility to the macrophage contact tumoricidal activity and NK-mediated cytolysis was investigated in MTT test. TNF-α-mediated tumor cell apoptosis as well as macrophage phagocytosis, oxidative metabolism, and CD206 expression after the treatment with conditioned media from normoxic and hypoxic tumor cells were studied by flow cytometry. Flow cytometry was also used to characterize dendritic cell maturity.

Results

When growing in vitro, LLC/R9 were characterized by slightly increased immunosuppressive cytokine gene expression. Transition to in vivo growth was associated with the enhancement of transcription of these genes in tumor cells. LLC/R9 cells had lowered sensitivity to contact-dependent macrophage-mediated cytotoxicity and to the TNFα-mediated apoptosis in vitro. Conditioned media from hypoxic LLC/R9 cells stimulated reactive oxygen species generation and CD206 expression in non-sensitized macrophages. Acquisition of drug resistance by LLC/R9 cells was associated with their increased sensitivity to NK-cell-mediated cytolysis. Meanwhile, the treatment of LLCR/9-bearing animals with generated ex vivo and loaded with LLC/R9 cell-lysate dendritic cells (DCs) resulted in profoundly enhanced tumor metastasizing.

Conclusion

Decreased sensitivity to macrophage cytolysis, polarizing effect on DCs maturation along with increased susceptibility to NK-cell cytotoxic action promote extensive local growth of chemoresistant LLC/R9 tumors in vivo, but hamper their metastasizing.

http://ift.tt/2BWBtDO

Progression to bone-marrow carcinomatosis and extraosseous legion during treatment with radium-223 for multiple bone metastases

Abstract

A 67-year-old man with metastatic prostate cancer presented with progression to castration-resistant prostate cancer. After sequential therapies with flutamide, estramustine phosphate, docetaxel, enzalutamide, and cabazitaxel for castration-resistant prostate cancer, radium-223 was initiated and continued up to 4 cycles. However, concurrently with radiological and clinical progressions, pancytopenia was observed due to bone-marrow carcinomatosis by prostatic adenocarcinoma. This case suggested that radium-223 should be employed at appropriated timing before appearances of extraosseous and bone-marrow lesions in addition to visceral metastasis.

http://ift.tt/2EinHNs

The Focused History and Physical - circa 100 BCE

Abstract

When modern physicians reflect on 'ancient medicine' or 'Greek medicine,' they typically think of Hippocrates and Galen. Few know of the raging, centuries-long intellectual debates among physicians about what exactly mattered in the treatment of illness, or about a group of physicians whose pattern-based, systematized approach to health and disease was a forerunner of how today's emergency medicine physicians evaluate and treat their patients.Methodist physicians (c. 100 BCE to 500 CE, active mostly in Rome but present throughout the Mediterranean world) were named after their "method" of healing.

This article is protected by copyright. All rights reserved.

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An overview on Vadimezan (DMXAA), the vascular disrupting agent

Abstract

Vascular disrupting agents (VDAs), a group of cancer remedies, can cause a specific and irreversible destruction of established tumor vessels, and the complete halt of blood flow in the tumor. DMXAA(ASA404) or Vadimezan, a flavone-acetic acid-based drug is the most promising VDAs that induces a rapid shutdown of blood flow in tumors but not in normal tissue. The exact mechanism of vascular disruption is unknown; however proposed direct and indirect mechanisms of action for DMXAA comprises: i) inducing apoptosis in endothelial cells; ii) hemorrhagic necrosis and ischemia in tumor; iii) release of serotonin (5-HT); vi) stimulation of innate immune system; v) production of inflammatory cytokines e.g. TNF, IL-6, GCSF, KC, IP-10, and MCP-1; vi) activation of NFκB and p38 (MAPK); vii) production of nitric oxide and viii) reducing tumor energetics and membrane turnover. Despite the remarkable results from preclinical and Phase I/II, DMXAA has failed in phase III clinical trials. The reason for this surprising discrepancy, among others, was discovered to be STING receptor variations between mice and humans. In this review, the development, the mechanisms of DMXAA action, the clinical trials, the combination therapy, and the future of this drug will be discussed.

This article is protected by copyright. All rights reserved.

This review highlights the characteristics of clinically used vascular disrupting agent drug, vadimezan, DMXAA (ASA404). Also development, and mechanisms of DMXAA action, and also the clinical trials, the combination therapy and the future of this drug is discussed.

http://ift.tt/2EggXzL

FDA Clears Stereotactic Radiotherapy System for Use in Treating Breast Cancer

December 22, 2017 -- Today, the U.S. Food and Drug Administration cleared a new noninvasive stereotactic radiotherapy system intended for use in treating cancer in breast tissue. "With today's clearance, patients will have access to a treatment...

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Difference in causes and prognostic factors of early death between cohorts with de novo and relapsed acute promyelocytic leukemia

Abstract

Early death (ED) remains the most critical issue in the current care of patients with acute promyelocytic leukemia (APL). Very limited data are available regarding ED in patients with relapsed APL. In this retrospective study, 285 de novo and 79 relapsed patients were included. All patients received single-agent arsenic trioxide as induction therapy. The differences in baseline clinical features, incidence, causes, and prognostic factors of ED were compared between the two patient cohorts. The relapse cohort exhibited a better overall condition than the de novo cohort upon hospital admission. The ED rate in the relapsed patients (24.1%) was somewhat higher than that in the de novo patients (17.9%), although the difference was not significant (P = 0.219). For both cohorts, hemorrhage was the main cause of ED, followed by differentiation syndrome, infection, and other causes. Increased serum creatinine level, older age, male sex, white blood cell (WBC) count > 10 × 10⁹/L, and fibrinogen < 1 g/L were independently risk factors for ED in the de novo patients, whereas WBC count > 10 × 10⁹/L, elevated serum uric acid level, and D-dimer > 4 mg/L were independent risk factors for ED in the relapsed patients. These data furnish clinically relevant information that might be useful for designing more appropriate risk-adapted treatment protocols aimed at reducing ED rate in patients with relapsed APL.

http://ift.tt/2lvNE3E

Association between hemorrhagic transformation after endovascular therapy and poststroke seizures

Summary

Objective

Endovascular therapy has recently become standard therapy for select patients with acute ischemic stroke. Infarcted brain tissue may undergo hemorrhagic transformation (HT) after endovascular therapy. We investigated the association between HT and occurrence of poststroke seizures in patients treated with endovascular therapy.

Methods

Consecutive patients treated with endovascular therapy for acute anterior circulation ischemic stroke were included. HT was assessed with computed tomography/magnetic resonance imaging (CT/MRI) at 24 h after stroke onset. Patients were followed for up to 2 years for seizure occurrence.

Results

A total of 205 (57.1% male) patients were analyzed. Median age was 69 years (interquartile range [IQR] 57-78). Among patients with HT, 17.9% (10/56) developed poststroke seizures compared with 4.0% (6/149) among those without HT (hazard ratio [HR] 5.52; 95% confidence interval [CI] 2.00-15.22; P = .001). The association remained significant after adjustment for cortical involvement, baseline National Institutes of Health Stroke Scale score, age and use of intravenous tissue plasminogen activator and clot retrieval (HR 4.85; 95% CI 1.60-14.76; P = .005). In patients who developed seizures within the follow-up period, median time to first seizure was 111 days (IQR 28-369) in patients with HT and 36 days (IQR 0.5-183) in patients without HT.

Significance

A patient who develops HT following endovascular therapy for acute ischemic stroke had a nearly 5 times higher rate of developing poststroke seizures within 2 years. HT may be used as an imaging biomarker for poststroke seizures.

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Cover, Ed Board and TOC

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Study protocol for a multicentre, randomised, controlled trial to assess the effectiveness of antimicrobial central venous catheters versus ordinary central venous catheters at reducing catheter related infections in critically ill Chinese patients

Introduction

Catheter use is associated with many complications and is an iatrogenic source of morbidity and mortality in intensive care units (ICU). The catheter being studied (Certofix Protect) was developed to reduce the risk of catheter related infections. This clinical trial will compare the safety and efficiency of Certofix Protect with that of an ordinary Certofix catheter.

Methods and analysis

In this multicentre trial, we will randomly assigned dual lumen central venous catheterisation (≥5 ds) in patients in the adult ICU to the antimicrobial central venous catheter (CVC) group or the ordinary CVC group. We plan to recruit 12–16 medical centres in China. Our main objective is to assess the effectiveness of antimicrobial CVCs in reducing catheter related bloodstream infection (CRBSI), all cause mortality, catheter colonisation, catheter related thrombosis and other catheter related complications. The primary outcome is the incidence of CRBSI.

Ethics and dissemination

The ethics committee of West China Hospital of Sichuan University has granted ethics approval for this study (27 January 2015). The results will be published in peer reviewed journals and presented at conferences.

Trial registration number

NCT02645682.

http://ift.tt/2Cqdn5A

Pneumonia diagnosis in childhood and incidence of leukaemia, lymphoma and brain cancer: a Danish nationwide cohort study

Objectives

There is an ongoing debate on the possible association between infections in early childhood and subsequent cancer risk, but it remains unclear if a hospital admission for infection is associated with risk of childhood cancer diagnosis. We examined if a hospital-based diagnosis of pneumonia was a clinical marker of the three most common childhood cancers.

Design

Population-based cohort study.

Setting

Denmark, hospital diagnoses, 1994–2013.

Methods

Using national health registries, we compared the observed incidence of leukaemia, lymphoma and brain cancer among 83 935 children with a hospital-based pneumonia diagnosis with that expected among children in the general population. We calculated absolute cancer risks and standardised incidence ratios (SIRs) as a measure of relative risk.

Results

The cancer SIRs were substantially increased during the first 6 months of follow-up; lymphoid leukaemia: 6.2 (95% CI 3.5 to 10.3); myeloid leukaemia: 14.8 (95% CI 6.0 to 30.6); Hodgkin's lymphoma: 60.8 (95% CI 26.2 to 120), non-Hodgkin's lymphoma: 15.9 (95% CI 5.2 to 37.2) and brain cancer: 4.4 (95% CI 1.9 to 8.7). The 6-month absolute risks of leukaemia, lymphoma and brain cancer were all low, reaching 0.05% when combined. An increased risk persisted beyond 5 years for non-Hodgkin's lymphoma and brain cancer. However, the 5-year absolute cancer risk was 0.14%.

Conclusions

The short-term incidence of leukaemia, lymphoma and brain cancer was higher than expected and persisted beyond 5 years for non-Hodgkin's lymphoma and brain cancer. However, the absolute cancer risk was low.

http://ift.tt/2ColAHc

Wait a minute? An observational cohort study comparing iron stores in healthy Swedish infants at 4 months of age after 10-, 60- and 180-second umbilical cord clamping

Background and objective

Umbilical cord blood (UCB) is a valuable stem cell source used for transplantation. Immediate umbilical cord (UC) clamping is widely practised, but delayed UC clamping is increasingly advocated to reduce possible infant anaemia. The aim of this study was to investigate an intermediate UC clamping time point and to evaluate iron status at the age of 4 months in infants who had the UC clamped after 60 s and compare the results with immediate and late UC clamping.

Design

Prospective observational study with two historical controls.

Setting

A university hospital in Stockholm, Sweden, and a county hospital in Halland, Sweden.

Methods

Iron status was assessed at 4 months in 200 prospectively recruited term infants whose UC was clamped 60 s after birth. The newborn baby was held below the uterine level for the first 30 s before placing the infant on the mother's abdomen for additional 30 s. The results were compared with data from a previously conducted randomised controlled trial including infants subjected to UC clamping at ≤10 s (n=200) or ≥180 s (n=200) after delivery.

Results

After adjustment for age differences at the time of follow-up, serum ferritin concentrations were 77, 103 and 114 µg/L in the 10, 60 and 180 s groups, respectively. The adjusted ferritin concentration was significantly higher in the 60 s group compared with the 10 s group (P=0.002), while the difference between the 60 and 180 s groups was not significant (P=0.29).

Conclusion

In this study of healthy term infants, 60 s UC clamping with 30 s lowering of the baby below the uterine level resulted in higher serum ferritin concentrations at 4 months compared with 10 s UC clamping. The results suggest that delaying the UC clamping for 60 s reduces the risk for iron deficiency.

Trial registration number

NCT01245296.

http://ift.tt/2DzQDiT

Azithromycin to prevent post-discharge morbidity and mortality in Kenyan children: a protocol for a randomised, double-blind, placebo-controlled trial (the Toto Bora trial)

Introduction

Child mortality due to infectious diseases remains unacceptably high in much of sub-Saharan Africa. Children who are hospitalised represent an accessible population at particularly high risk of death, both during and following hospitalisation. Hospital discharge may be a critical time point at which targeted use of antibiotics could reduce morbidity and mortality in high-risk children.

Methods and analysis

In this randomised, double-blind, placebo-controlled trial (Toto Bora Trial), 1400 children aged 1–59 months discharged from hospitals in Western Kenya, in Kisii and Homa Bay, will be randomised to either a 5-day course of azithromycin or placebo to determine whether a short course of azithromycin reduces rates of rehospitalisation and/or death in the subsequent 6-month period. The primary analysis will be modified intention-to-treat and will compare the rates of rehospitalisation or death in children treated with azithromycin or placebo using Cox proportional hazard regression. The trial will also evaluate the effect of a short course of azithromycin on enteric and nasopharyngeal infections and cause-specific morbidities. We will also identify risk factors for postdischarge morbidity and mortality and subpopulations most likely to benefit from postdischarge antibiotic use. Antibiotic resistance in Escherichia coli and Streptococcus pneumoniae among enrolled children and their primary caregivers will also be assessed, and cost-effectiveness analyses will be performed to inform policy decisions.

Ethics and dissemination

Study procedures were reviewed and approved by the institutional review boards of the Kenya Medical Research Institute, the University of Washington and the Kenyan Pharmacy and Poisons Board. The study is being externally monitored, and a data safety and monitoring committee has been assembled to monitor patient safety and to evaluate the efficacy of the intervention. The results of this trial will be published in peer-reviewed scientific journals and presented at relevant academic conferences and to key stakeholders.

Trial registration number

NCT02414399.

http://ift.tt/2Dz3vWm

Association between total dose of ritodrine hydrochloride and pulmonary oedema in twin pregnancy: a retrospective cohort study in Japan

Objective

Pulmonary oedema is recognised as a severe side effect of ritodrine hydrochloride. Recently, the number of twin pregnancies has been increasing. Few studies have reported the association between total dose of ritodrine hydrochloride prior to delivery and pulmonary oedema in twin pregnancy. We aimed to examine this association and determine the optimal cut-off threshold of total ritodrine hydrochloride dose to predict the incidence of pulmonary oedema in twin pregnancy based on obstetric records.

Design

Retrospective cohort study.

Setting

Yamanashi Prefectural Central Hospital, Japan.

Participants

Two hundred and twenty-six women with twin pregnancy who delivered at Yamanashi Prefectural Central Hospital between September 2009 and November 2016.

Methods

The obstetric records of the participants were analysed. We defined 1 unit of ritodrine hydrochloride as 72 mg per 24 hours continuous transfusion at 50 µg/min to calculate the dose of ritodrine used for tocolysis.

Outcome measures

Multivariable logistic regression analysis was performed to examine the association between total dose of ritodrine hydrochloride used for threatened preterm labour and pulmonary oedema, while controlling for potential confounding factors. Then, a receiver–operating characteristic curve was used to determine the optimal cut-off of total ritodrine dose to predict pulmonary oedema incidence.

Results

Mean maternal age was 32 (range, 18–46) years; 143 participants were nulliparous (63.3%), 109 had (48.2%) term deliveries and 194 (85.8%) had caesarean deliveries. The overall incidence of pulmonary oedema was 13.7% (31/226). Multivariable analysis showed that the total dose of ritodrine was significantly associated with pulmonary oedema (adjusted OR 1.02; 95% CI 1.004 to 1.03). The best cut-off point to predict the incidence of pulmonary oedema was 26 units (1872 mg) (sensitivity, 61.3%; specificity, 87.8%).

Conclusion

Our results suggest that consideration of the total dose of ritodrine hydrochloride is helpful in the management of patients with threatened preterm labour in twin pregnancy.

http://ift.tt/2DxjFQ0

Pharmacological interventions for preventing post-operative atrial fibrillation in patients undergoing cardiac surgery: a network meta-analysis protocol

Introduction

Postoperative atrial fibrillation (POAF) is the most common complication following cardiac surgery, and randomised clinical trials (RCTs) and systematic reviews have been conducted to compare and evaluate different pharmacological interventions for preventing POAF. This study aimed to explore the effect of different pharmacological interventions for prophylaxis against POAF after cardiac surgery using network meta-analysis (NMA).

Methods and analysis

A systematic search will be performed in PubMed, EMBASE and the Cochrane Library to identify RCTs, systematic reviews, meta-analyses or NMA of different pharmacological interventions for POAF. We will evaluate the risk of bias of the included RCTs according to the Cochrane Handbook V.5.1.0, and use GRADE to assess the quality of evidence. Standard pairwise meta-analysis, trial sequential analysis and Bayesian network meta-analysis will be used to compare the efficacy of different pharmacological interventions.

Ethics and dissemination

Ethics approval and patient consent are not required as this study is a meta-analysis based on published studies. The results of this NMA and trial sequential analysis will be submitted to a peer-reviewed journal for publication.

Protocol registration number

CRD42017067492.

http://ift.tt/2CpQcIB

Development and validation of a priori risk model for extensive white matter lesions in people age 65 years or older: the Dijon MRI study

Objectives

The objective was to develop and validate a risk model for the likelihood of extensive white matter lesions (extWML) to inform clinicians on whether to proceed with or forgo diagnostic MRI.

Design

Population-based cohort study and multivariable prediction model.

Setting

Two representative samples from France.

Participants

Persons aged 60–80 years without dementia or stroke. Derivation sample n=1714; validation sample n=789.

Primary and secondary outcome measures

Volume of extWML (log cm³) was obtained from T2-weighted images in a 1.5 T scanner. 20 candidate risk factors for extWML were evaluated with the C-statistic. Secondary outcomes in validation included incident stroke over 12 years follow-up.

Results

The multivariable prediction model included six clinical risk factors (C-statistic=0.61). A cut-off of 7 points on the multivariable prediction model yielded the optimum balance in sensitivity 63.7% and specificity 54.0% and the negative predictive value was high (81.8%), but the positive predictive value was low (31.5%). In further validation, incident stroke risk was associated with continuous scores on the multivariable prediction model (HR 1.02; 95% CI 1.01 to 1.04, P=0.02) and dichotomised scores from the multivariable prediction model (HR 1.28; 95% CI 1.02 to 1.60, P=0.03).

Conclusions

A simple clinical risk equation for WML constituted by six variables can inform decisions whether to proceed with or forgo brain MRI. The high-negative predictive value demonstrates potential to reduce unnecessary MRI in the population aged 60–80 years.

http://ift.tt/2CqzYil

Prevalence of mental ill health, traumas and postmigration stress among refugees from Syria resettled in Sweden after 2011: a population-based survey

Objectives

To estimate the prevalence of and associations between anxiety, depression, post-traumatic stress disorder (PTSD), low subjective well-being (SWB), potential traumas and postmigration stress among refugees from Syria resettled in Sweden.

Design

A cross-sectional and population-based questionnaire study based on a known and complete sample frame. The survey included multiple measures of mental ill health and factors of particular relevance for refugees. Weighted analyses were conducted to calculate representative prevalence rates and associations. Associations were investigated through a series of logistic regression analyses. All analyses were supplemented with robust 95% CIs.

Setting

Sweden.

Participants

A random sample of 1215 individuals (response rate 30.4%) from Syria aged 18–64 years that were granted residency in Sweden on grounds of asylum between 2011 and 2013.

Main outcome measures

Anxiety, depression, PTSD and low SWB were assessed through Hopkins Symptom Checklist, Harvard Trauma Questionnaire and WHO-5 Well-being Index, using established cut-offs.

Results

A majority of the participants met the criteria for at least one of the studied types of mental ill health, and the comorbidity was high. Depression was the most the common type with 40.2% (95% CI 36.9% to 43.3%), followed by low SWB with 37.7% (95% CI 34.8% to 40.1%), anxiety with 31.8% (95% CI 29.2% to 34.7%) and PTSD with 29.9% (95% CI 27.2% to 32.6%). Refugee-related potentially traumatic events (PTEs) experienced before or during migration was common as was substantial levels of postmigration stress. Most types of refugee-related PTEs, especially being exposed to interpersonal violence, and postmigration stress were associated with increased risks for anxiety, depression, low SWB and PTSD.

Conclusions

Mental ill health, in terms of anxiety, depression, low SWB and PTSD, are highly elevated and comorbid among refugees from Syria. Increased attention from multiple societal sectors to adequately support Syrian refugees' mental health needs, promoting recovery and reducing postmigration stress are needed.

http://ift.tt/2DyAHNO

Effect of whole-body vibration exercise in preventing falls and fractures: a systematic review and meta-analysis

Objective

To investigate the effect of whole-body vibration exercise (WBV) on fracture risk in adults ≥50 years of age.

Design

A systematic review and meta-analysis calculating relative risk ratios, fall rate ratio and absolute weighted mean difference using random effects models. Heterogeneity was estimated using I² statistics, and the Cochrane Collaboration's risk of bias tool and the GRADE approach were used to evaluate quality of evidence and summarise conclusions.

Data sources

The databases PubMed, Embase and the Cochrane Central Register from inception to April 2016 and reference lists of retrieved publications.

Eligibility criteria for selecting studies

Randomised controlled trials examining the effect of WBV on fracture risk in adults ≥50 years of age. The primary outcomes were fractures, fall rates and the proportion of participants who fell. Secondary outcomes were bone mineral density (BMD), bone microarchitecture, bone turnover markers and calcaneal broadband attenuation (BUA).

Results

15 papers (14 trials) met the inclusion criteria. Only one study had fracture data reporting a non-significant fracture reduction (risk ratio (RR)=0.47, 95% CI 0.14 to 1.57, P=0.22) (moderate quality of evidence). Four studies (n=746) showed that WBV reduced the rate of falls with a rate ratio of 0.67 (95% CI 0.50 to 0.89, P=0.0006; I²=19%) (moderate quality of evidence). Furthermore, data from three studies (n=805) found a trend towards falls reduction (RR=0.76, 95% CI 0.48 to 1.20, P=0.24; I²=24%) (low quality of evidence). Finally, moderate to low quality of evidence showed no overall effect on BMD and only sparse data were available regarding microarchitecture parameters, bone turnover markers and BUA.

Conclusions

WBV reduces fall rate but seems to have no overall effect on BMD or microarchitecture. The impact of WBV on fractures requires further larger adequately powered studies. This meta-analysis suggests that WBV may prevent fractures by reducing falls.

PROSPERO registration number

CRD42016036320; Pre-results.

http://ift.tt/2Cpi7Is

Patterns of routine primary care for osteoarthritis in the UK: a cross-sectional electronic health records study

Objective

To determine common patterns of recorded primary care for osteoarthritis (OA), and patient and provider characteristics associated with the quality of recorded care.

Design

An observational study nested within a cluster-randomised controlled trial.

Setting

Eight UK general practices who were part of the Management of Osteoarthritis in Consultations study.

Participants

Patients recorded as consulting within the eight general practices for clinical OA.

Primary outcomes

Achievement of seven quality indicators of care (pain/function assessment, information provision, exercise/weight advice, analgesics, physiotherapy), recorded through an electronic template or routinely recorded in the electronic healthcare records, was identified for patients aged ≥45 years consulting over a 6-month period with clinical OA. Latent class analysis was used to cluster patients based on care received. Clusters were compared on patient and clinician-level characteristics.

Results

1724 patients (median by practice 183) consulted with clinical OA. Common patterns of recorded quality care were: cluster 1 (38%, High) received most quality indicators of care; cluster 2 (11%, Moderate) had pain and function assessment, and received or were considered for other indicators; cluster 3 (17%, Low) had pain and function assessment, and received or were considered for paracetamol or topical non-steroidal anti-inflammatory drugs; cluster 4 (35%, None) had no recorded quality indicators. Patients with higher levels of recorded care consulted a clinician who saw more patients with OA, consulted multiple times and had less morbidity. Those in the High cluster were more likely to have recorded diagnosed OA and have knee/hip OA.

Conclusions

Patterns of recorded care for OA fell into four natural clusters. Appropriate delivery of core interventions and relatively safe pharmacological options for OA are still not consistently recorded as provided in primary care. Further research to understand clinical recording behaviours and determine potential barriers to quality care alongside effective training for clinicians is needed.

Trial registration number

ISRCTN06984617; Results.

http://ift.tt/2CqhK0m

Neighbourhood socioeconomic status and cross-sectional associations with obesity and urinary biomarkers of diet among New York City adults: the heart follow-up study

Objective

To determine whether neighbourhood socioeconomic status (SES) is associated with body mass index (BMI), waist circumference (WC) and biomarkers of diet (urinary sodium and potassium excretion).

Design

A cross-sectional study.

Setting

The data reported were from the 2010 Heart Follow-up Study, a population-based representative survey of 1645 adults.

Participants

Community-dwelling diverse residents of New York City nested within 128 neighbourhoods (zip codes).

Primary and secondary outcome measures

BMI (kg/m²) and WC (inches) were measured during in-home visits, and 24-hour urine sample was collected to measure biomarkers of diet: sodium (mg/day) and potassium (mg/day), with high sodium and low potassium indicative of worse diet quality.

Results

After adjusting for individual-level characteristics using multilevel linear regressions, low versus high neighbourhood SES tertile was associated with 1.83 kg/m² higher BMI (95% CI 0.41 to 3.98) and 251 mg/day lower potassium excretion (95% CI –409 to 93) among women only, with no associations among men (P values for neighbourhood SES by sex interactions <0.05).

Conclusion

Our results suggest that women may be particularly vulnerable to the effects of a socioeconomically disadvantaged neighbourhood. Future neighbourhood research should explore sex differences, as these can inform tailored interventions.

Trial registration number

NCT01889589; Results.

http://ift.tt/2CrJKkb

Open peroral endoscopic myotomy for achalasia with failed Heller myotomy

Abstract

In May 2017, a 55-year-old man was referred to our endoscopy center because of dysphagia and chest pain. The patient with a history of failed Heller myotomy was diagnosed as a recurrence of achalasia (type II) with an Eckardt score of 13. Selective myotomy was achieved by peroral endoscopic myotomy without a submucosal tunnel for this case. We describe this technique as open peroral endoscopic myotomy(O-POEM) (Fig 1, 2).

This article is protected by copyright. All rights reserved.

http://ift.tt/2llQR6C

The usefulness of argon plasma coagulation ablation subsequent to endoscopic snare papillectomy for ampullary adenoma

Abstract

Background and aim

Endoscopic snare papillectomy (ESP) is an effective treatment for ampullary adenoma. Argon plasma coagulation (APC) is widely used as an additional method to control bleeding or ablate the residual tumor. However, the efficacy of this procedure has not yet been fully evaluated. This study aimed to evaluate the usefulness of APC as an additional method to ESP.

Methods

The patients who underwent ESP for ampullary adenoma between September 2005 and September 2015 were retrospectively reviewed. Using propensity score matching, we compared short- and long-term outcomes between ESP with additional APC group and ESP only group. Primary outcome was early post-ESP adverse events (AEs), and secondary outcome were late AEs and recurrence.

Results

Among 109 patients, additional APC was performed in 59 (54.1%) patients. After matching, 41 patients were included in both groups, respectively. Bleeding rate was significantly lower in ESP+APC group than ESP only group (7.3% vs. 31.7%, odds ratio = 0.180, P<0.01). However, there were no significant differences in other procedure-related early AEs such as pancreatitis (12.2% vs. 19.5%, P = 0.365), cholangitis (2.4% vs. 9.8%, P = 0.198), and perforation (2.4% vs. 2.4%, P = 1.000) between ESP+APC group and ESP only group. During the follow-up period (mean 904±868 days), papillary stricture (9.8% vs. 4.9%, P = 0.405) and recurrence rates (24.4% vs. 24.4%, P = 0.797) were not significantly different between ESP+APC group and ESP only group.

Conclusions

Additional APC during ESP may have beneficial effect by decreasing bleeding rate without harmful effect.

This article is protected by copyright. All rights reserved.

http://ift.tt/2ltqVF4

RING-finger protein 6 amplification activates JAK/STAT3 pathway by modifying SHP-1 ubiquitylation and associates with poor outcome in colorectal cancer

Objective The E3 ubiquitin ligase RNF6 (RING-finger protein 6) plays a crucial role in carcinogenesis. However, the copy number and expression of RNF6 were rarely reported in colorectal cancer (CRC). We aimed to explore the mechanical, biological and clinical role of RNF6 in CRC initiation and progression. Design The copy number and expression of RNF6 were analyzed from Tumorscape and The Cancer Genome Atlas (TCGA) datasets. Gene expressions were examined by real time PCR, western blot and immunohistochemical staining. Gene expression profiling studies were performed to identify pivotal genes regulated by RNF6. Biological function of RNF6 on tumor growth and metastasis was detected in vivo and vitro. Role of RNF6 in modulating SHP-1 expression was examined by co-immunoprecipitation and confocal microscopy respectively. Results The copy number of RNF6 was significantly amplified in CRC and the amplification was associated with RNF6 expression level. Amplification and overexpression of RNF6 positively correlated with CRC patients with poor prognosis. GSEA analysis revealed cell proliferation and invasion-related genes were enriched in RNF6 high-expressed CRC cells as well as in patients from TCGA dataset. Down-regulation of RNF6 impaired the CRC cell proliferation and invasion in vitro and vivo. RNF6 may activate JAK/STAT3 pathway and increase pSTAT3 levels by inducing the ubiquitination and degradation of SHP-1. Conclusions Genomic amplification drives RNF6 overexpression in CRC. RNF6 may be a novel biomarker in colorectal carcinogenesis, and RNF6 may increase pSTAT3 level via promoting SHP-1 ubiquitylation and degradation. Targeting the RNF6/SHP-1/STAT3 axis provides a potential therapeutic option for RNF6-amplified tumors.

http://ift.tt/2zO6Z5d

Genomics-Driven Precision Medicine for Advanced Pancreatic Cancer - Early Results from the COMPASS Trial.

Purpose: To perform real time whole genome sequencing (WGS) and RNA sequencing (RNASeq) of advanced pancreatic ductal adenocarcinoma (PDAC) to identify predictive mutational and transcriptional features for better treatment selection.  Experimental Design: Patients with advanced PDAC were prospectively recruited prior to first-line combination chemotherapy. Fresh tumor tissue was acquired by image guided percutaneous core biopsy for WGS and RNASeq. Laser capture microdissection was performed for all cases. Primary endpoint was feasibility to report WGS results prior to first disease assessment CT scan at 8 weeks. The main secondary endpoint was discovery of patient subsets with predictive mutational and transcriptional signatures. Results:Sixty three patients underwent a tumor biopsy between December 2015 and June 2017. WGS and RNASeq were successful in 62 (98%) and 60 (95%), respectively. Genomic results were reported at a median of 35 days (range 19-52 days) from biopsy, meeting the primary feasibility endpoint. Objective responses to first line chemotherapy were significantly better in patients with the classical PDAC RNA subtype compared to those with the basal-like subtype (P=0.004). The best progression free survival was observed in those with classical subtype treated with m-FOLFIRINOX. GATA6 expression in tumor measured by RNA in situ hybridization was found to be a robust surrogate biomarker for differentiating classical and basal-like PDAC subtypes. Potentially actionable genetic alterations were found in 30% of patients. Conclusions:Prospective genomic profiling of advanced PDAC is feasible and our early data indicate that chemotherapy response differs among patients with different genomic/transcriptomic subtypes.

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CD47 Blockade as an Adjuvant Immunotherapy for Resectable Pancreatic Cancer

Purpose: Patients with pancreatic ductal adenocarcinoma (PDAC) who undergo surgical resection and adjuvant chemotherapy have an expected survival of only two years due to disease recurrence, frequently in the liver. We investigated the role of liver macrophages in progression of PDAC micrometastases to identify adjuvant treatment strategies that could prolong survival. Experimental Design: A murine splenic injection model of hepatic micrometastatic PDAC was used with five patient-derived PDAC tumors. The impact of liver macrophages on tumor growth was assessed by 1) depleting mouse macrophages in nude mice with liposomal clodronate injection, and 2) injecting tumor cells into nude vs. NOD-scid-gamma mice. Immunohistochemistry and flow cytometry were used to measure CD47 ("don't eat me signal") expression on tumor cells and characterize macrophages in the tumor microenvironment. In vitro engulfment assays and mouse experiments were performed with CD47-blocking antibodies to assess macrophage engulfment of tumor cells, progression of micrometastases in the liver and mouse survival. Results: In vivo clodronate depletion experiments and NOD-scid-gamma mouse experiments demonstrated that liver macrophages suppress the progression of PDAC micrometastases. Five patient-derived PDAC cell lines expressed variable levels of CD47. In in vitro engulfment assays, CD47-blocking antibodies increased the efficiency of PDAC cell clearance by macrophages in a manner which correlated with CD47 receptor surface density. Treatment of mice with CD47-blocking antibodies resulted in increased time-to-progression of metastatic tumors and prolonged survival. Conclusions: These findings suggest that following surgical resection of PDAC, adjuvant immunotherapy with anti-CD47 antibody could lead to substantially improved outcomes for patients.

http://ift.tt/2zO8lN1

Sequencing of Linkage Region on Chromosome 12p11 Identifies PKP2 as a Candidate Gene for Left Ventricular Mass in Dominican Families

Increased left ventricular mass (LVM) is an intermediate phenotype for cardiovascular disease (CVD) and a predictor of stroke. Using families from the Dominican Republic, we have previously shown LVM to be heritable and found evidence for linkage to chromosome 12p11. Our current study aimed to further characterize the QTL by sequencing the 1 LOD unit down region in ten families from the Dominican Republic with evidence for linkage to LVM. Within this region, we tested 5,477 common variants (CVs; minor allele frequency [MAF] ≥5%) using the QTDT test. Gene-based analyses were performed to test rare variants (RVs; MAF<5%) in 181 genes using the family-based sequence kernel association test. A sample of 618 unrelated Dominicans from the Northern Manhattan Study (NOMAS) and 12 Dominican families with Exome Array data were used for replication analyses. The most strongly associated CV with evidence for replication was rs1046116 (Discovery families p=9.0x10^-4; NOMAS p=0.03; replication families p=0.46), a missense variant in PKP2. In non-synonymous RV analyses, PKP2 was one of the most strongly associated genes (p=0.05) with suggestive evidence for replication in NOMAS (p=0.05). PKP2 encodes the plakophilin 2 protein and is a desmosomal gene implicated in arrythmogenic right ventricular cardiomyopathy and recently in arrhythmogenic left ventricular cardiomyopathy, which makes PKP2 an excellent candidate gene for LVM. In conclusion, sequencing of our previously reported QTL identified common and rare variants within PKP2 to be associated with LVM. Future studies are necessary to elucidate the role these variants play in influencing LVM.

http://ift.tt/2zOmR7x

Understanding EMS Scheduling Software & The Web of Information That Runs Your Business

There are many different web-based products for just about any service you can imagine in the EMS and public service industry. Most organizations use an HR Management system for on-boarding employees, managing their employment status and providing benefit enrollment. There are more and more HRIS vendors that have "do it all" systems with the addition of online time clock & attendance ...

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Platinum Educational Group Prepares for New CoAEMSP Requirements

GRAND RAPIDS, MI — Platinum Educational Group understands the struggles and obstacles that are presented to EMS educators when it pertains to accreditation. EMS training institutes, particularly paramedic programs, face stringent challenges like the NREMT Portfolio (where applicable), on-site reviews, and most recently the upcoming Appendix G requirements from Committee on Accreditation of Educational ...

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A Case of Fatal Pulmonary Hypoplasia with Congenital Diaphragmatic Hernia, Thoracic Myelomeningocele, and Thoracic Dysplasia

AJP Rep 2017; 07: e234-e237
DOI: 10.1055/s-0037-1615791

Background Congenital diaphragmatic hernia (CDH) is fatal in severe cases of pulmonary hypoplasia. We experienced a fatal case of pulmonary hypoplasia due to CDH, thoracic myelomeningocele (MMC), and thoracic dysplasia. This constellation of anomalies has not been previously reported. Case Report A male infant with a prenatal diagnosis of thoracic MMC with severe hydrocephalus and scoliosis was born at 36 weeks of gestation. CDH was found after birth and the patient died of respiratory failure due to pulmonary hypoplasia and persistent pulmonary hypertension of the newborn at 30 hours of age despite neonatal intensive care. An autopsy revealed a left CDH without herniation of the liver or stomach into the thoracic cavity, severe hydrocephalus, Chiari malformation type II, MMC with spina bifida from Th4 to Th12, hemivertebrae, fused ribs, deformities of the thoracic cage and legs, short trunk, and agenesis of the left kidney. Conclusion We speculate that two factors may be associated with the severe pulmonary hypoplasia: decreased thoracic space due to the herniation of visceral organs caused by CDH and thoracic dysplasia due to skeletal deformity and severe scoliosis.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

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Ineffective Erythropoiesis: Anemia and Iron Overload

Stress erythropoiesis (SE) is characterized by an imbalance in erythroid proliferation and differentiation under increased demands of erythrocyte generation and tissue oxygenation. β-thalassemia represents a chronic state of SE, called ineffective erythropoiesis (IE), exhibiting an expansion of erythroid-progenitor pool and deposition of alpha chains on erythrocyte membranes, causing cell death and anemia. Concurrently, there is a decrease in hepcidin expression and a subsequent state of iron overload. There are substantial investigative efforts to target increased iron absorption under IE. There are also avenues for targeting cell contact and signaling within erythroblastic islands under SE, for therapeutic benefits.

http://ift.tt/2EdKmdN

Machine Guns Underwater

Imagine you are on a fishing trip on the Colorado River Delta where the river flows into the Sea of Cortez by Baja California. You spot a section of water that seems to be churned up and muddy, almost muddy like someone was mixing cocoa powder to make hot chocolate. You get a bit closer, and all of a sudden you instinctively duck under the nearest deck chair. It sounds like someone is firing a machine gun at you. But the sound does not stop and only keeps getting louder.

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Isolated central nervous system post-transplant lymphoproliferative disorder in a pediatric patient: a case report with pathobiological perspective

Abstract

Isolated central nervous system post-transplant lymphoproliferative disorder (ICNS-PTLD) in pediatric patients is a distinctly rare entity without accepted diagnostic criteria or treatment recommendations. We present a case of an 8-year-old male with a prior history of a kidney transplant who developed and ICNS-PTLD. We highlight the pathobiology and diagnostic features with a brief review of the literature on these rare cases. There is a complex interplay between CD30, Epstein Barr Virus and MYC as part of lymphocyte transformation leading to PTLD. In the appropriate clinical setting, CD30 and EBV positivity along with normal MYC expression are highly predictive of CNS-PTLD over a Primary CNS lymphoma. ICNS-PTLD has only been rarely reported in children. The faithful diagnosis is necessary for prognostication and to accrue data for treatment recommendations.

http://ift.tt/2BTF19Z

The structure of the FACT-Cog v3 in cancer patients, students, and older adults

The FACT-Cog version 3 questionnaire is designed to assess perceived cognitive function and impact on quality of life in cancer patients.

http://ift.tt/2EfVXc2

Old Friends: Maintaining the Physician-Patient Connection in the 21st Century

I've had multiple roles in my medical career, including traditional bench academic, clinical academic, private practitioner, and administrator. But I've always worked in teaching hospitals, instructing students, residents, and for a good amount of time, fellows. Interaction with patients has changed, particularly with the presence of the electronic medical record (EMR), where the computer is now the third person in the room, often sitting between the doctor and patient. But these are not musings of an old man wistfully remembering the days before computers.

http://ift.tt/2ChDUo1

Morphometric diagnosis of Glossina palpalis (Diptera: Glossinidae) population structure in Ghana

This study aimed to identify isolated population(s) of Glossina palpalis in Ghana using geometric morphometrics to evaluate variations in wing-shape and size between populations of the fly from three regions.

http://ift.tt/2CpqbJn

Use of the Hippocratic or other professional oaths in UK medical schools in 2017: practice, perception of benefit and principlism

This paper concerns the continued use of the Hippocratic Oath in United Kingdom (UK) medical schools. A survey of all UK medical schools looked at which schools use the Oath, which variants they use, and what ...

http://ift.tt/2Dywcm6

Acupuncture for patients with mild to moderate Alzheimer’s disease: a randomized controlled trial

Alzheimer's disease (AD) is the most common cause of dementia. However, none of medical treatment can stop or reverse the underlying neurodegenerative of AD at present. Acupuncture has attracted more and more ...

http://ift.tt/2zNCn3I

Phoyunnanin E inhibits migration of non-small cell lung cancer cells via suppression of epithelial-to-mesenchymal transition and integrin αv and integrin β3

The conversion of the epithelial phenotype of cancer cells into cells with a mesenchymal phenotype-so-called epithelial–mesenchymal transition (EMT)-has been shown to enhance the capacity of the cells to disse...

http://ift.tt/2C9s53H

Acacia hydaspica R. Parker prevents doxorubicin-induced cardiac injury by attenuation of oxidative stress and structural Cardiomyocyte alterations in rats

The use of doxorubicin (DOX) an anthracycline antineoplastic agent is withdrawn due to its cardio-toxic side effects. Oxidative stress has been recognized as the primary cause of DOX induced cardiotoxicity. We...

http://ift.tt/2zNC74K

Danshen extract circumvents drug resistance and represses cell growth in human oral cancer cells

Danshen is a common traditional Chinese medicine used to treat neoplastic and chronic inflammatory diseases in China. However, the effects of Danshen on human oral cancer cells remain relatively unknown. This ...

http://ift.tt/2C9scfD

Correction to: Ficus sycomorus extract reversed behavioral impairment and brain oxidative stress induced by unpredictable chronic mild stress in rats

After the publication of this article [1] it came to our attention that Harquin Simplice Foyet was incorrectly included as Harquin Simplice Harquin Foyet. The corrected name is included in the author list. The...

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Chromatin Immunoprecipitation (ChIP) of Histone Modifications from Saccharomyces cerevisiae

Here, we describe a protocol for chromatin immunoprecipitation of modified histones from the budding yeast Saccharomyces cerevisiae. Immunoprecipitated DNA is subsequently used for quantitative PCR to interrogate the abundance and localization of histone post-translational modifications throughout the genome.

http://ift.tt/2lkTDZH

Post-ERCP infection and its epidemiological and clinical characteristics in a large Chinese tertiary hospital: a 4-year surveillance study

Endoscopic retrograde cholangiopancreatography (ERCP) is widely performed as a treatment for biliary and pancreatic illness in China; however, there are few data available regarding post-ERCP infections. This ...

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Urinary pathogenic bacterial profile, antibiogram of isolates and associated risk factors among pregnant women in Ambo town, Central Ethiopia: a cross-sectional study

Urinary tract infection (UTI) is a well-known bacterial infection posing serious health problem in pregnant women. A study was conducted in pregnant women with the objectives of estimating prevalence of UTI, d...

http://ift.tt/2EgfSYn

Human Bronchial Epithelial Cell–derived Factors from Severe Asthmatic Subjects Stimulate Eosinophil Differentiation

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 99-106, January 2018.


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Regulators of G-Protein Signaling as Asthma Therapy?

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 7-9, January 2018.


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RGS4 Overexpression in Lung Attenuates Airway Hyperresponsiveness in Mice

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 89-98, January 2018.


http://ift.tt/2BUJDwp

Genetic Variation in MAP3K1 Associates with Ventilator-Free Days in Acute Respiratory Distress Syndrome

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 117-125, January 2018.


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A Circulating MicroRNA Signature Serves as a Diagnostic and Prognostic Indicator in Sarcoidosis

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 40-54, January 2018.


http://ift.tt/2BUJzNb

High-Mobility Group Box 1 Upregulates MUC5AC and MUC5B Expression in Primary Airway Epithelial Cells

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 126-128, January 2018.


http://ift.tt/2ClGzx2

Oxygen Administration Improves Survival but Worsens Cardiopulmonary Functions in Chlorine-exposed Rats

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 107-116, January 2018.


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January Highlights/Papers by Junior Investigators/NIH News

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page i-i, January 2018.


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Sirtuin1 Protects against Systemic Sclerosis–related Pulmonary Fibrosis by Decreasing Proinflammatory and Profibrotic Processes

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 28-39, January 2018.


http://ift.tt/2BUe6uI

Deletion of c-FLIP from CD11bhi Macrophages Prevents Development of Bleomycin-induced Lung Fibrosis

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 66-78, January 2018.


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Immunomodulatory Cell Therapy to Target Cystic Fibrosis Inflammation

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 12-20, January 2018.


http://ift.tt/2BUJqJD

Biomarkers in Sarcoidosis: Can microRNAs Fill the Gap?

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 1-2, January 2018.


http://ift.tt/2CggY8H

Hypercapnic Acidosis Regulates Mer Tyrosine Kinase Receptor Shedding and Activity

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 132-134, January 2018.


http://ift.tt/2BT5yUW

β2-Agonists Enhance Asthma-Relevant Inflammatory Mediators in Human Airway Epithelial Cells

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 128-132, January 2018.


http://ift.tt/2CjO5s1

Chlorine Countermeasures: Supplemental Oxygen Equals Supplemental Lung Injury?

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 10-11, January 2018.


http://ift.tt/2BU7xYU

CD34 Differentially Regulates Contractile and Noncontractile Elements of Airway Reactivity

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 79-88, January 2018.


http://ift.tt/2Cnempi

Monocyte-derived Alveolar Macrophages: The Dark Side of Lung Repair?

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 5-6, January 2018.


http://ift.tt/2BWnI8l

Is Asthma Paying the Toll?

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 3-4, January 2018.


http://ift.tt/2ClseAv

Toll-Like Receptor 7/8 Ligand, S28463, Suppresses Ascaris suum–induced Allergic Asthma in Nonhuman Primates

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 55-65, January 2018.


http://ift.tt/2BWnzSl

Semaphorins and Their Roles in Airway Biology: Potential as Therapeutic Targets

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 1, Page 21-27, January 2018.


http://ift.tt/2ClPNJy

Palliative Care Planner: A Pilot Study to Evaluate Acceptability and Usability of an Electronic Health Records System-integrated, Needs-targeted App Platform

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 59-68, January 2018.


http://ift.tt/2Cq18G8

Facilitators and Barriers to Positive Airway Pressure Adherence for Adolescents. A Qualitative Study

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 83-88, January 2018.


http://ift.tt/2Dxf6Fg

Long-Term Oxygen Therapy: The Three Big Questions

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 14-15, January 2018.


http://ift.tt/2CmmIet

Distinct Phenotypes of Smokers with Fixed Airflow Limitation Identified by Cluster Analysis of Severe Asthma

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 33-41, January 2018.


http://ift.tt/2CqcWs1

Severe Airflow Obstruction in a Man with Stomatitis and Lymphadenopathy

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 102-106, January 2018.


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Fitting Positive Airway Pressure Adherence into Teenage Life: Don’t Push It!

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 22-23, January 2018.


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Combined Pulmonary Fibrosis and Emphysema

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 110-112, January 2018.


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Mind the Gap: Addressing Provider-Level Barriers to Lung Cancer Screening

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 20-21, January 2018.


http://ift.tt/2zMCFry

Comments on “Stressing the Brain...Acute Respiratory Distress Syndrome”

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 113-114, January 2018.


http://ift.tt/2zLs7ci

Early Respiratory Bacterial Detection and Antistaphylococcal Antibiotic Prophylaxis in Young Children with Cystic Fibrosis

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 42-48, January 2018.


http://ift.tt/2zMCEE0

Reply: A New Direction: Sleep and Neuropsychological Impairment after Critical Illness

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 114-114, January 2018.


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The Public Health Conundrum of Coal Mining

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 11-13, January 2018.


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Discovering Pediatric Asthma Phenotypes on the Basis of Response to Controller Medication Using Machine Learning

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 49-58, January 2018.


http://ift.tt/2zNHe4I

Patient Perceptions of the Adequacy of Supplemental Oxygen Therapy. Results of the American Thoracic Society Nursing Assembly Oxygen Working Group Survey

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 24-32, January 2018.


http://ift.tt/2CbIuEU

Subacute Respiratory Illness with Peripheral Pulmonary Opacities

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 107-109, January 2018.


http://ift.tt/2Dyhvj7

Reply: Comments on “Stressing the Brain…Acute Respiratory Distress Syndrome”

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 115-115, January 2018.


http://ift.tt/2CoLsCW

The U.S. Food and Drug Administration's Experience with Ivacaftor in Cystic Fibrosis. Establishing Efficacy Using In Vitro Data in Lieu of a Clinical Trial

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 1-2, January 2018.


http://ift.tt/2DwODI8

Out of One, Many: Moving beyond a Single Guideline toward Personalized Asthma Care for Obese Children

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 16-17, January 2018.


http://ift.tt/2Cp3wgh

The Value and Application of the 6-Minute-Walk Test in Idiopathic Pulmonary Fibrosis

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 3-10, January 2018.


http://ift.tt/2Cp3rJv

The Long-Term Oxygen Treatment Trial for Chronic Obstructive Pulmonary Disease: Rationale, Design, and Lessons Learned

Annals of the American Thoracic Society, Volume 15, Issue 1, Page 89-101, January 2018.


http://ift.tt/2DvNvo0

A Simple and Low-cost Assay for Measuring Ambulation in Mouse Models of Muscular Dystrophy

This protocol describes a flexible, low-cost system for measuring mouse ambulation in an open field activity assay. We show that a 6-minute ambulation assay based on this system detects a decrease in voluntary movement in mdx mice, and accurately distinguishes improvement in a muscle-specific rescue of these animals.

http://ift.tt/2DwxjTr

FirstNet now available for first responders across the U.S.

All 50 states, two territories and Washington, D.C. have joined FirstNet in order to give first responders access to the wireless broadband network

http://ift.tt/2DvvmGU

Hepatitis B virus infection in hilly/mountainous regions of southeastern China: a locality-dependent epidemiology

The overall prevalence of hepatitis B virus (HBV) infection in China is declining. The purpose of this study was to use a community-based epidemiological study to update the infection status of hepatitis B vir...

http://ift.tt/2lk0LW7

Influenza vaccine effectiveness against influenza-related hospitalization during a season with mixed outbreaks of four influenza viruses: a test-negative case-control study in adults in Canada

The Serious Outcomes Surveillance (SOS) Network was established to monitor seasonal influenza complications among hospitalized Canadian adults and to assess the effectiveness of influenza vaccination against s...

http://ift.tt/2ltUyGe

The aetiologies of central nervous system infections in hospitalised Cambodian children

Central nervous system (CNS) infections are an important cause of childhood morbidity and mortality. The aetiologies of these potentially vaccine-preventable infections have not been well established in Cambodia.

http://ift.tt/2lk1syG

An evaluation of a recombinant multiepitope based antigen for detection of Toxoplasma gondii specific antibodies

The inefficiency of the current tachyzoite antigen-based serological assays for the serodiagnosis of Toxoplasma gondii infection mandates the need for acquirement of reliable and standard diagnostic reagents. Rec...

http://ift.tt/2lsAB2N

Improved performance of Xpert MTB/RIF assay on sputum sediment samples obtained from presumptive pulmonary tuberculosis cases at Kibong’oto infectious diseases hospital in Tanzania

The introduction of Xpert MTB/RIF assay (Xpert) has significantly improved diagnosis of Tuberculosis (TB) in resource limited human immunodeficiency virus (HIV) endemic settings. We aimed to modify the Xpert p...

http://ift.tt/2lhuP4K

Visualizing Intracellular SNARE Trafficking by Fluorescence Lifetime Imaging Microscopy

This protocol describes a new method allowing for the quantitative visualization of complex formation of SNARE proteins, based on Förster resonance energy transfer, and fluorescence lifetime imaging microscopy.

http://ift.tt/2EgPlKQ

The relationship between lower limb muscle volume and body mass in ambulant individuals with bilateral cerebral palsy

Individuals with cerebral palsy have smaller muscle volumes normalised to body mass than their typically developing peers. The aim of this study is to investigate the relationship between lower limb muscle vol...

http://ift.tt/2lsNg5Q

Nucleoli cytomorphology in cutaneous melanoma cells – a new prognostic approach to an old concept

The nucleolus is an organelle that is an ultrastructural element of the cell nucleus observed in H&E staining as a roundish body stained with eosin due to its high protein content. Changes in the nucleoli cyto...

http://ift.tt/2C9YJCr

An Interpretable Machine Learning Model for Accurate Prediction of Sepsis in the ICU

Objectives: Sepsis is among the leading causes of morbidity, mortality, and cost overruns in critically ill patients. Early intervention with antibiotics improves survival in septic patients. However, no clinically validated system exists for real-time prediction of sepsis onset. We aimed to develop and validate an Artificial Intelligence Sepsis Expert algorithm for early prediction of sepsis. Design: Observational cohort study. Setting: Academic medical center from January 2013 to December 2015. Patients: Over 31,000 admissions to the ICUs at two Emory University hospitals (development cohort), in addition to over 52,000 ICU patients from the publicly available Medical Information Mart for Intensive Care-III ICU database (validation cohort). Patients who met the Third International Consensus Definitions for Sepsis (Sepsis-3) prior to or within 4 hours of their ICU admission were excluded, resulting in roughly 27,000 and 42,000 patients within our development and validation cohorts, respectively. Interventions: None. Measurements and Main Results: High-resolution vital signs time series and electronic medical record data were extracted. A set of 65 features (variables) were calculated on hourly basis and passed to the Artificial Intelligence Sepsis Expert algorithm to predict onset of sepsis in the proceeding T hours (where T = 12, 8, 6, or 4). Artificial Intelligence Sepsis Expert was used to predict onset of sepsis in the proceeding T hours and to produce a list of the most significant contributing factors. For the 12-, 8-, 6-, and 4-hour ahead prediction of sepsis, Artificial Intelligence Sepsis Expert achieved area under the receiver operating characteristic in the range of 0.83–0.85. Performance of the Artificial Intelligence Sepsis Expert on the development and validation cohorts was indistinguishable. Conclusions: Using data available in the ICU in real-time, Artificial Intelligence Sepsis Expert can accurately predict the onset of sepsis in an ICU patient 4–12 hours prior to clinical recognition. A prospective study is necessary to determine the clinical utility of the proposed sepsis prediction model. The opinions or assertions contained herein are the private ones of the author/speaker and are not to be construed as official or reflecting the views of the Department of Defense, the Uniformed Services University of the Health Sciences, or any other agency of the U.S. Government. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). Drs. Nemati, Stanley, and Clifford received support for article research from the National Institutes of Health (NIH). Dr. Nemati's institution received funding from the NIH, award number K01ES025445. Dr. Holder received funding from CR Bard, Inc. Dr. Buchman's institution received funding from the Henry M. Jackson Foundation for his role as site director in Surgical Critical Care Institute, www.sc2i.org, funded through the Department of Defense's Health Program – Joint Program Committee 6/Combat Casualty Care (USUHS HT9404-13-1-0032 and HU0001-15-2-0001); from Society of Critical Care Medicine for his role as Editor-in-Chief of "Critical Care Medicine"; and from Philips Corporation (unrestricted educational grant to a physician education association in South Korea so he could present the results of his research in eICU). Dr. Buchman received support for article research from the Henry M Jackson Foundation. Ms. Ramzi has disclosed that she does not have any potential conflicts of interest. For information regarding this article, E-mail: shamim.nemati@alum.mit.edu Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://ift.tt/2zNfq0k

Update of a Systematic Review of Autoresuscitation After Cardiac Arrest

Objectives: There has been a growth in publications focusing on the phenomena of autoresuscitation in recent years. In 2010, we systematically reviewed the medical literature with the primary objective of summarizing the evidence on the timing of autoresuscitation. Healthcare professionals have continued to voice concerns regarding the potential for autoresuscitation. With this in mind, the objective of this brief report is to update the results of our original review of autoresuscitation. Data Sources: We applied the same search strategy described in our original article to update our findings to include articles published from January 2009 to September 2016. Study Selection and Data Extraction: We screened an additional 1,859 citations, after duplicates were removed, and then assessed 46 full-text articles for eligibility, from which 15 studies were included for data extraction. Data Synthesis: During the time period of this review, there have been 1) 10 additional adult and three pediatric case reports of autoresuscitation in patients after cessation of cardiopulmonary resuscitation; in those cases with continuous monitoring and confirmation of circulation, the longest events are reported to be 10 and 2 minutes, respectively for adults and children; 2) six adults (4%, total n = 162) with autoresuscitation events reported from two observational studies and one chart review of patients undergoing withdrawal of life-sustaining therapy; the longest time reported to be 89 seconds with electrocardiogram and invasive arterial blood pressure monitoring and 3 minutes with electrocardiogram monitoring only; 3) 12 pediatric patients studied with vital sign monitoring during withdrawal of life-sustaining therapy without any reports of autoresuscitation. Conclusions: Although case reports of autoresuscitation are hampered by variability in observation and monitoring techniques, autoresuscitation has now been reported in adults and children, and there appears to be a distinction in timing between failed cardiopulmonary resuscitation and withdrawal of life-sustaining therapy. Although additional prospective studies are required to clarify the frequency and predisposing factors associated with this phenomenon, clinical decision-making regarding patient management under uncertainty is required nonetheless. Both adult and pediatric healthcare professionals should be aware of the possibility of autoresuscitation and monitor their patients accordingly before diagnosing death. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). Supported, in part, by Canadian Blood Services. Ms. Hornby received funding from Canadian Blood Services (consultant) and disclosed that she is the Project Manager for a research program in deceased organ donation, funded by the Canadian Institutes of Health Research. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: lhornby@uottawa.ca Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://ift.tt/2zMvRKr

Explaining the Origin of Three-Membrane-Bound Plastids in Dinoflagellates and Euglenophytes: Kleptoplastidy via Myzocytosis?

http://ift.tt/2ChR9F8

Methylphenidate disrupts cytoskeletal homeostasis and reduces membrane-associated lipid content in juvenile rat hippocampus

Abstract

Although methylphenidate (MPH) is ubiquitously prescribed to children and adolescents, the consequences of chronic utilization of this psychostimulant are poorly understood. In this study, we investigated the effects of MPH on cytoskeletal homeostasis and lipid content in rat hippocampus. Wistar rats received intraperitoneal injections of MPH (2.0 mg/kg) or saline solution (controls), once a day, from the 15th to the 44th day of age. Results showed that MPH provoked hypophosphorylation of glial fibrillary acidic protein (GFAP) and reduced its immunocontent. Middle and high molecular weight neurofilament subunits (NF-M, NF-H) were hypophosphorylated by MPH on KSP repeat tail domains, while NFL, NFM and NFH immunocontents were not altered. MPH increased protein phosphatase 1 (PP1) and 2A (PP2A) immunocontents. MPH also decreased the total content of ganglioside and phospholipid, as well as the main brain gangliosides (GM1, GD1a, and GD1b) and the major brain phospholipids (sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine). Total cholesterol content was also reduced in the hippocampi of juvenile rats treated with MPH. These results provide evidence that disruptions of cytoskeletal and lipid homeostasis in hippocampus of juvenile rats are triggers by chronic MPH treatment and present a new basis for understanding the effects and consequences associated with chronic use of this psychostimulant during the development of the central nervous system.

http://ift.tt/2lim7Dm

Swyer-James Syndrome

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 130-131, January 1, 2018.


http://ift.tt/2lryNqD

The z-Score Does Not Predict Mortality Because of Confounding by Age

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 141-141, January 1, 2018.


http://ift.tt/2liBQCs

Psychological Outcomes after Critical Illness. Is It Time to Rethink Our Paradigm?

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 6-7, January 1, 2018.


http://ift.tt/2lqH6Db

Pulmonology in Pregnancy

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 127-129, January 1, 2018.


http://ift.tt/2liBKuA

Fluticasone Furoate, Vilanterol, and Lung Function Decline in Patients with Moderate Chronic Obstructive Pulmonary Disease and Heightened Cardiovascular Risk

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 47-55, January 1, 2018.


http://ift.tt/2llilZN

Airway Closure in Acute Respiratory Distress Syndrome: An Underestimated and Misinterpreted Phenomenon

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 132-136, January 1, 2018.


http://ift.tt/2lr5XH5

Weight-adjusted Intravenous Reslizumab in Severe Asthma with Inadequate Response to Fixed-Dose Subcutaneous Mepolizumab

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 38-46, January 1, 2018.


http://ift.tt/2liBCeA

Total Airway Count on Computed Tomography and the Risk of Chronic Obstructive Pulmonary Disease Progression. Findings from a Population-based Study

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 56-65, January 1, 2018.


http://ift.tt/2lsu7B0

A Novel Drug-Eluting Indwelling Pleural Catheter for the Management of Malignant Effusions

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 136-138, January 1, 2018.


http://ift.tt/2lj9rw2

The Case of Missing Airways in Chronic Obstructive Pulmonary Disease

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 4-6, January 1, 2018.


http://ift.tt/2liRLR7

A Phase 2 Randomized Controlled Study of Tralokinumab in Subjects with Idiopathic Pulmonary Fibrosis

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 94-103, January 1, 2018.


http://ift.tt/2liRD45

Airway Closure Could Be Confirmed by Electrical Impedance Tomography

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 138-141, January 1, 2018.


http://ift.tt/2lpqvjh

Exosome-based Therapy for Bronchopulmonary Dysplasia

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 10-12, January 1, 2018.


http://ift.tt/2liRsFX

Reply to Vanjare et al.: The z-Score Does Not Predict Mortality Because of Confounding by Age

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 141-142, January 1, 2018.


http://ift.tt/2lq7QUk

Airway Mucosal Host Defense Is Key to Genomic Regulation of Cystic Fibrosis Lung Disease Severity

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 79-93, January 1, 2018.


http://ift.tt/2liRkpX

Reaching for the Holy Grail of Chronic Obstructive Pulmonary Disease Outcomes. Can Medications Modify Lung Function Decline?

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 2-4, January 1, 2018.


http://ift.tt/2lsQw0P

Reply to Gilbert et al.: The Impact of the ASAP Trial: Maybe We Shouldn’t Act So Quickly

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 143-144, January 1, 2018.


http://ift.tt/2liRfCF

Eosinophilic and Noneosinophilic Asthma

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 22-37, January 1, 2018.


http://ift.tt/2lq7HQM

Do Randomized Clinical Trials Always Provide Certain Results? The Case of Tralokinumab in Idiopathic Pulmonary Fibrosis

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 1, Page 9-10, January 1, 2018.


http://ift.tt/2lqGZYh

Principles and methods of in-silico prioritization of non-coding regulatory variants

Abstract

Over a decade of genome-wide association, studies have made great strides toward the detection of genes and genetic mechanisms underlying complex traits. However, the majority of associated loci reside in non-coding regions that are functionally uncharacterized in general. Now, the availability of large-scale tissue and cell type-specific transcriptome and epigenome data enables us to elucidate how non-coding genetic variants can affect gene expressions and are associated with phenotypic changes. Here, we provide an overview of this emerging field in human genomics, summarizing available data resources and state-of-the-art analytic methods to facilitate in-silico prioritization of non-coding regulatory mutations. We also highlight the limitations of current approaches and discuss the direction of much-needed future research.

http://ift.tt/2zLAch3

Outcomes of previously untreated elderly patients with AML: a propensity score-matched comparison of clofarabine vs. FLAG

Abstract

The 5-year overall survival (OS) in patients ≥ 60 years old with acute myeloid leukemia (AML) remains < 10%. Clofarabine-based induction (CLO) provides an alternative to low-intensity therapy (LIT) and palliative care for this population, but supporting data are conflicted. Recently, our institution adopted the FLAG regimen (fludarabine, cytarabine, and granulocyte colony-stimulating factor) based on data reporting similar outcomes to CLO in elderly patients with AML unable to tolerate anthracycline-based induction. We retrospectively analyzed the efficacy and safety of patients ≥ 60 years old with AML treated with FLAG or CLO over the past 10 years. We performed a propensity score match that provided 32 patients in each group. Patients treated with FLAG had a higher CR/CRi rate (65.6 vs. 37.5%, P = 0.045) and OS (7.9 vs. 2.8 months, P = 0.085) compared to CLO. Furthermore, FLAG was better tolerated with significantly less grade 3/4 toxicities and a shorter duration of neutropenia (18.5 vs. 30 days, P = 0.002). Finally, we performed a cost analysis that estimated savings to be $30,000–45,000 per induction with FLAG. Our study supports the use of FLAG both financially and as an effective, well-tolerated high-dose treatment regimen for elderly patients with AML. No cases of cerebellar neurotoxicity occurred.

http://ift.tt/2lq1Law

Fusobacterium May Help Colorectal Cancer Grow and Spread

Fusobacterium, found in the stomach and intestines, may help fuel the growth of colorectal cancer and metastases. In a mouse model of colorectal cancer, using antibiotics to kill these bacteria slowed tumor growth.

http://ift.tt/2pXs0KQ

The Changing Landscape of Lynch Syndrome due to PMS2 Mutations

Abstract

DNA repair pathways are essential for cellular survival as our DNA is constantly under assault from both exogenous and endogenous DNA damaging agents. Five major mammalian DNA repair pathways exist within a cell to maintain genomic integrity. Of these, the DNA mismatch repair (MMR) pathway is highly conserved among species and is well documented in bacteria. In humans, the importance of MMR is underscored by the discovery that a single mutation in any one of four genes within the MMR pathway (MLH1, MSH2, MSH6 and PMS2) results in Lynch syndrome (LS). LS is an autosomal dominant condition that predisposes individuals to a higher incidence of many malignancies including colorectal, endometrial, ovarian, and gastric cancers. In this review, we discuss the role of PMS2 in the MMR pathway, the evolving testing criteria used to identify variants in the PMS2 gene, the LS phenotype as well as the autosomal recessive condition called Constitutional Mismatch Repair Deficiency syndrome, and current methods used to elucidate the clinical impact of PMS2 mutations.

http://ift.tt/2pVh0hc

Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice

Abstract

Although genetic revolution of recent years has vastly expanded a list of genes implicated in epilepsies, complex architecture of epilepsy genetics is still largely unknown, consequently, universally accepted workflows for epilepsy genetic testing in a clinical practice are missing. We present a comprehensive NGS-based diagnostic approach addressing both the clinical and genetic heterogeneity of disorders involving epilepsy or seizures. A bioinformatic panel of 862 epilepsy- or seizure-associated genes was applied to Mendeliome (4813 genes) or whole-exome sequencing data as a first stage, while the second stage included untargeted variant interpretation. Eighty-six consecutive patients with epilepsy or seizures associated with neurodevelopmental disorders and/or congenital malformations were investigated. Of the 86 probands, 42 harbored pathogenic and likely pathogenic variants, giving a diagnostic yield of 49%. Two patients were diagnosed with pathogenic copy number variations and two had causative mitochondrial DNA variants. Eleven patients (13%) were diagnosed with diseases with specific treatments. Besides, genomic approach in diagnostics had multiple additional benefits due to mostly non-specific, overlapping, not full-blown phenotypes and abilities to diagnose novel and ultra rare epilepsy-associated diseases. Likely pathogenic variants were identified in SOX5 gene, not previously associated with epilepsy, and UBA5, a recently associated with epilepsy gene.

http://ift.tt/2EbgXRv

New Research From Psychological Science

Read about the latest research published in Psychological Science:

Does Smile Intensity in Photographs Really Predict Longevity? A Replication and Extension of Abel and Kruger (2010)

Michael Dufner, Martin Brümmer, Joanne M. Chung, Pia M. Drewke, Christophe Blaison, and Stefan C. Schmukle

Past research has suggested that positive affectivity is associated with longevity. Many of the studies finding this connection have examined a small to medium timeframe (less than 30 years), but one of the few studies examining this relationship over a longer period was conducted by Abel and Kruger (2010). In this study, the researchers analyzed pictures of U.S. professional baseball players who were active in 1952. The authors used the players' smiles in the photographs as a proxy for positive affectivity and examined how long they had lived (as of 2009). The researchers found that players who showed a full smile were half as likely to die in a given year as players who did not smile. In the current study, the authors attempted to replicate and extend these findings by analyzing three samples: one almost identical to that in the Abel and Kruger (2010) study, a nonoverlapping sample from the same cohort, and all players in the database. The pictures were assessed by human coders and by automatic computer-based emotion-recognition programs. The researchers found that the results failed to replicate, in that indicators of positive affectivity did not predict longevity after birth year was controlled as a covariate.

Mothers' Neural and Behavioral Responses to Their Infants' Distress Cues: The Role of Secure Base Script Knowledge
Ashley M. Groh and Katherine C. Haydon

Children who have sensitive caregivers are likely to represent the attachment relationship as structured around a secure base of support, a representation that guides how they process social information later in life. However, some individuals may form less adaptive attachment representations. Do these representations influence how mothers attend to their infants' distress cues? To find out, the authors used a narrative completion task to gauge the degree to which participating mothers held a secure-base attachment representation. They also had each mother complete an attention task in which she viewed images of her infant making different facial expressions and pressed a button whenever she saw the target expression. Physiological data recorded via EEG revealed that mothers whose narratives lacked a secure-base structure showed a larger P3b amplitude (an event-related potential component) when attending to their infants' distress expressions and were less likely to identify these expressions compared with mothers whose narratives included a secure base. Because P3b amplitude is thought to indicate the attentional resources engaged in a task, the authors conclude that lacking a secure-base attachment representation may make it more difficult for some mothers to attend to their infants' distress.

Early Conceptual Understanding of Cardinality Predicts Superior School-Entry Number-System Knowledge

David C. Geary, Kristy vanMarle, Felicia W. Chu, Jeffrey Rouder, Mary K. Hoard, and Lara Nugent

Most children's first mathematical insight is that number words represent unique and specific quantities (i.e., cardinal values). This understanding may emerge as early as age 3 or as late as age 6, meaning that children who acquire cardinality insight later may fall behind their peers in mathematical competence and other academic outcomes. The researchers tested children's mathematical abilities when they began preschool at ages 3 and 4 and throughout the next 2 years, measuring skills including verbal counting, cardinality understanding, and numerical recognition. When the children were 6 and 7 years old, the researchers asked them to solve some simple addition problems and some more complex math problems without pencil and paper; the children then described how they solved each problem. Statistical analyses revealed that children who understood that number words represent specific quantities earlier showed greater knowledge of number systems and mathematics achievement at follow-up compared with peers whose understanding of cardinality emerged later. This suggests that the age at which children acquire the concept of cardinal value is central to their mathematical development and school readiness.

http://ift.tt/2DwE3B0

Overcoming hypoxia-induced tumor radioresistance in non-small cell lung cancer by targeting DNA-dependent protein kinase in combination with carbon ion irradiation

Abstract

Background

Hypoxia-induced radioresistance constitutes a major obstacle for a curative treatment of cancer. The aim of this study was to investigate effects of photon and carbon ion irradiation in combination with inhibitors of DNA-Damage Response (DDR) on tumor cell radiosensitivity under hypoxic conditions.

Methods

Human non-small cell lung cancer (NSCLC) models, A549 and H1437, were irradiated with dose series of photon and carbon ions under hypoxia (1% O₂) vs. normoxic conditions (21% O₂). Clonogenic survival was studied after dual combinations of radiotherapy with inhibitors of DNA-dependent Protein Kinase (DNAPKi, M3814) and ATM serine/threonine kinase (ATMi).

Results

The OER at 30% survival for photon irradiation of A549 cells was 1.4. The maximal oxygen effect measured as survival ratio was 2.34 at 8 Gy photon irradiation of A549 cells. In contrast, no significant oxygen effect was found after carbon ion irradiation. Accordingly, the relative effect of 6 Gy carbon ions was determined as 3.8 under normoxia and. 4.11 under hypoxia. ATM and DNA-PK inhibitors dose dependently sensitized tumor cells for both radiation qualities. For 100 nM DNAPKi the survival ratio at 4 Gy more than doubled from 1.59 under normoxia to 3.3 under hypoxia revealing a strong radiosensitizing effect under hypoxic conditions. In contrast, this ratio only moderately increased after photon irradiation and ATMi under hypoxia. The most effective treatment was combined carbon ion irradiation and DNA damage repair inhibition.

Conclusions

Carbon ions efficiently eradicate hypoxic tumor cells. Both, ATMi and DNAPKi elicit radiosensitizing effects. DNAPKi preferentially sensitizes hypoxic cells to radiotherapy.

http://ift.tt/2lrzuAp

Letter to the Editor regarding the article “Prevalence of Hepatitis A Virus Antibody in Portuguese Travelers: A New Paradigm”

N/A.

http://ift.tt/2Duut1g

Post-Traumatic Diaphragmatic Hernia: Limitations of Non-Invasive Ventilation

N/A.

http://ift.tt/2CluFAw

Letter to the Editor: The Clear and Present Danger to Portuguese Travelers to the Middle East Region

N/A.

http://ift.tt/2DvvSVw

Infectious Mononucleosis and Cholestatic Hepatitis: A Rare Association

Infectious mononucleosis is one of the major clinical manifestations of Epstein-Barr virus infection. In this syndrome, elevation of liver transaminase levels is common but cholestasis is rare, with few cases described in the literature. We present the case of a 14-year-old female adolescent, admitted to the Emergency Room with fever, odynophagia and cervical adenomegaly. She was treated with amoxicillin and two days later he presented with jaundice. The analytical evaluation was compatible with cholestatic hepatitis and abdominal ultrasound revealed hepatosplenomegaly without dilatation of the bile ducts. The diagnosis of Epstein-Barr virus infection was confirmed by the presence of serological markers. This case aims to raise awareness of a rare manifestation of a common infectious agent and, consequently, to the inclusion of acute Epstein-Barr virus infection in the differential diagnosis of pediatric cholestatic hepatitis.

http://ift.tt/2ClurcE

Letter to the Editor: Colonic Perforation

N/A.

http://ift.tt/2Dw8Uxq

Lead Poisoning: Myoclonus Following Welding Exposure

N/A.

http://ift.tt/2Cn8cTQ

Limited Health Literacy in Portugal Assessed with the Newest Vital Sign

Introduction: In Portugal, health literacy has started to be addressed through national policies, but research on the topic is still scarce. We aimed to estimate the prevalence and sociodemographic correlates of limited health literacy in Portugal using an existing health literacy instrument, the Newest Vital Sign.
Materials and Methods: Following cross-cultural adaptation of the instrument, a sample of 249 participants was evaluated to assess reliability and construct validity of the Newest Vital Sign; the latter was tested assuming physicians would score highest, followed by health researchers, then by engineering researchers and finally by laypersons from the general population. We applied this validated version in a representative sample of 1544 Portuguese-speaking residents in Portugal aged between 16 and 79 years and quantified the associations between limited health literacy and sociodemographic characteristics.
Results: The instrument showed high reliability (Cronbach's α = 0.85). Health-related occupation showed association with higher scores in the Newest Vital Sign (p trend < 0.001). The prevalence of limited health literacy in the Portuguese population was 72.9% (95% CI: 69.4 - 76.4). We found no differences between men and women, but persons with limited health literacy were significantly older (p < 0.001) and less educated (p < 0.001).
Discussion: The burden of limited health literacy in Portugal is higher than that in other European countries. It should drive a universal precautions approach to health communication at all levels of the health system.
Conclusion: We validated a brief and simple instrument and estimated the prevalence of limited health literacy in the literate Portuguese population at roughly three out of four people.

http://ift.tt/2DvpzRT

Retroperitoneal Cellular Angiofibroma: A Rare Gynecological Entity

Cellular angiofibroma is a mesenchymal tumor, described in 1997, without gender preference, that usually appears at age 40. The vulvovaginal area is the most common site in women, mimicking vulvar benign tumors, like Bartholin gland cyst. However, there are a few described cases of a deep or extra-pelvic angiofibroma. Excision is the treatment of choice and the recurrence rate appears to be low. We present the case of a woman with a heterogeneous tumor in the right adnexial region. At the surgery, a retroperitoneal tumor was excised and the histopathological tissue analysis revealed a cellular angiofibroma.

http://ift.tt/2ClXI7g

Effects of Speech Therapy in Hospitalized Patients with Post-Stroke Dysphagia: A Systematic Review of Observational Studies

Introduction: Since dysphagia may be one of the brain post-stroke consequences, the objective of this study was to analyze the average recovery time of patients with cerebrovascular accident and dysphagia subjected to speech therapy in a hospital bed.
Material and Methods: Systematic review performed following the 'Preferred Reporting Items is Systematic Reviews and MetaAnalyses' instructions. The search was performed in different electronic databases, without restriction of time and language. The studies were evaluated regarding their methodological quality.
Results: Of 5671 titles, five studies were included. 176 patients with stroke and dysphagia were obtained (aged between 22 and 91 years old – average: 68.95), with no preference regarding gender. Improvement occurred in 84.26% of the subjects and the recovery time was between one and ninety days (average: 22 days). Randomization, blinding, loss to follow-up and withdrawal were not performed with control group in any study.
Discussion: The success of rehabilitation of oropharyngeal dysphagia as a post-stroke sequela will depend on the extent, location of the neurological lesion and early intervention in the hospital bed. Despite the recognition of health professionals about the importance of swallowing rehabilitation for these patients, there is a lack of studies that support an evidence-based practice, although the results point to improvements in this regard.
Conclusion: Speech therapy in hospital bed in post-stroke hospitalized patients with dysphagia seems to bring satisfactory results in the short-term, revealing the importance of diagnosis and early intervention in these cases.

http://ift.tt/2DwD2ZD

Selection of Donor-Recipient Pairs in Renal Transplantation: Comparative Simulation Results

Introduction: Implemented in 2007 by Ordinance No. 6357, allocation rules of cadaveric donor kidneys seek to distribute equitably a scarce community resource to patients who can improve their survival and quality of life. As stated in the aforementioned ordinance these rules must be updated whenever the state of the art recommends it. The objective of this work is to evaluate and compare three cadaveric donor allocation models: scoring criteria of ordinance nº 6537/2007 (model 1); similar to the previous model but with a lower score for the dialysis time (model 2); and a model adapted from the previously proposed color allocation system (model 3).
Material and Methods: For the purpose of this analysis we generated data about 70 cadaveric donors taking into account information published regarding blood group distribution and human leucocyte antigens allelic and haplotype frequencies of Portuguese voluntary donors. We generated also data for a simulated waiting list of 500 first-time kidney transplant candidates.
Results: We observed fewer candidates selected by model 3 with more than 3 human leucocyte antigens mismatches (39.3%) when compared to those selected by model 1 with more than 3 human leucocyte antigens mismatches (57.1%, p < 0.01).
Discussion: In our analysis, model 3 selects transplant candidates with a lower number of human leucocyte antigens mismatches when compared to the adapted rules for kidney allocation of Ordinance No. 6537/2007 (model 1) without penalizing candidates with a longer time on dialysis.
Conclusion: The analysis and discussion of the best rules for allocation of such a scarce resource as organs from deceased donors should be a continuous and adaptive process inherent to transplant candidate's waiting list evolution and mutation.

http://ift.tt/2CmXDjM

Anaesthesia in Dental Medicine with Local Infiltrative Anaesthetic Technique Versus Diploe Anaesthesia Delivery Systems: Efficacy and Behaviour, an Experimental Study

Introduction: This study aimed to compare the analgesic efficacy and the influence of local infiltrative anesthesia techniques, with diploe anesthesia, on the cardiac rhythm
Material and Methods: We selected 32 healthy volunteers who were given both anaesthetic techniques on tooth 1.4 (0.45 mL of lidocaine with adrenaline, 1:80 000). In the first phase, the volunteers underwent periapical infiltrative anaesthesia. In the second phase, diploe anaesthesia was performed with a QuickSleeper® device. The parameters analysed were pulp response to the electrical test and heart rate of the participants. These parameters were evaluated on five different occasions: before anaesthesia (t0), immediately after anaesthesia (t1), 15 minutes later (t15), 30 minutes later (t30) and 60 minutes later (t60). Statistical analysis of the data was performed using SPSS 2.0 software, with α = 0.05.
Results: With the diploe anaesthesia, a level of analgesia was obtained faster. There was a slight increase in heart rate soon after administration of diploe anaesthesia, which stabilized after t15 of the procedure. This technique still proved to be painless.
Conclusion: Diploe anaesthesia demonstrated better results in terms of analgesia than the infiltrative anaesthesia. It has been reported to be easy, safe and an effective procedure that allows anaesthesia in almost all clinical situations. This approach may offer particular advantages for endodontic therapy, providing greater comfort for the patient.

http://ift.tt/2DwRII9

Injuries in Portuguese Amateur Youth Football Players: A Six Month Prospective Descriptive Study

Introduction: This study analyzed the incidence and characteristics of injuries sustained by amateur youth football players in Portugal during season 2015 - 2016.
Material and Methods: This is an observational descriptive study. We analyzed Portuguese youth football players' injuries over six months of a season. A total of 529 players were divided according to their age in two groups (Under-17 and Under-19). Data on injuries were collected.
Results: Throughout all 62 062.0 hours of exposure recorded, 248 injuries were reported in 173 different players. The average incidence of injury was 3.87 (95% CI = 2.81; 4.94) per 1000 hours of football exposure. There was a significantly higher average incidence of injury during matches – 14.22 (95% CI = 10.35; 18.09) per 1000 hours of exposure – when compared to the average incidence of injury during training – 2.06 (95% CI = 1.22; 2.90) per 1000 hours of exposure. This significance was also observed when the comparison was made within each age group. A traumatic mechanism was involved in 76.6% of all the injuries, while overuse was reported in 12.9%. The most common type was the injury that affected muscles and tendons (52.8%). The body location most commonly affected by injuries was the thigh (24.6%).
Discussion: Even though is essential a better characterization of Portuguese athletes of younger age groups such as those discussed in this study, the results of the studied population are in agreement with the existing literature. However, this study provides more information that may be important to better target the Portuguese athletes' training for injury prevention.
Conclusion: This study provides descriptive data on injuries developed in a subpopulation of Portuguese amateur youth football players that could represent a focus for future prevention.

http://ift.tt/2Cnkmw1

Kidney Allocation: New Contributions to an Ongoing Challenge

N/A.

http://ift.tt/2DvFY8B

Analysis of the Cochrane Review: Early Discharge Hospital at Home. Cochrane Database Syst Rev. 2017;6:CD000356.

Hospital at home is a service that provides active treatment by healthcare professionals in the patient's home for a condition that otherwise would require acute hospital in-patient care. However, the clinical benefit of this intervention and its effect on health costs are not established. This Cochrane systematic review aimed to assess the effectiveness and costs of managing patients with hospital at home compared with inpatient hospital care. A systematic review of the literature was carried out by searching the following databases to 9 January 2017: Cochrane Effective Practice and Organization of Care Group (EPOC) register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, EconLit and clinical trials registries. Thirty-two randomized trials (2 of which unpublished), including 4746 patients, were included. The present review provides insufficient objective evidence of economic benefit (through a reduction in hospital length of stay) or improved health outcomes.

http://ift.tt/2Dve6le

Fremanezumab for Preventive Treatment of Migraine

Fremanezumab is a humanized monoclonal antibody targeting calcitonin gene–related peptide (CGRP). It is administered monthly via SQ injection.

In this NEJM study, fremanezumab was effective as a preventive treatment for chronic migraine: http://ift.tt/2k9DoB2

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Functional requirement of a wild-type allele for mutant IDH1 to suppress anchorage-independent growth through redox homeostasis

Abstract

Mutations of isocitrate dehydrogenase 1 (IDH1) gene are most common in glioma, arguably preceding all known genetic alterations during tumor development. IDH1 mutations nearly invariably target the enzymatic active site Arg132, giving rise to the predominant IDH1^R132H. Cells harboring IDH1^R132H -heterozygous mutation produce 2-hydroxyglutarate (2-HG), which results in histone and DNA hypermethylation. Although exogenous IDH1^R132H transduction has been shown to promote anchorage-independent growth, the biological role of IDH1^R132H in glioma remains debatable. In this study, we demonstrate that heterozygous IDH1^R132H suppresses but hemizygous IDH1^R132H promotes anchorage-independent growth. Whereas genetic deletion of the wild-type allele in IDH1^R132H -heterozygous cells resulted in a pronounced increase in neurosphere genesis, restoration of IDH1 expression in IDH1^R132H -hemizygous cells led to the contrary. Conversely, anchorage-independent growth was antagonistic to the mutant IDH1 function by inhibiting gene expression and 2-HG production. Furthermore, we identified that in contrast to IDH1^R132H -hemizygous neurosphere, IDH1^R132H -heterozygous cells maintained a low level of reducing power to suppress neurosphere genesis, which could be bypassed, however, by the addition of reducing agent. Taken together, these results underscore the functional importance of IDH1 mutation heterozygosity in glioma biology and indicate functional loss of mutant IDH1 as an escape mechanism underlying glioma progression and the pathway of redox homeostasis as potential therapeutic targets.

http://ift.tt/2pW1dP2