Αρχειοθήκη ιστολογίου

Αναζήτηση αυτού του ιστολογίου

Παρασκευή 3 Νοεμβρίου 2017

Effects of 30 Years of Disuse on Exceptional Memory Performance

Abstract

In the mid-1980s, Dario Donatelli (DD) participated in a laboratory study of the effects of around 800 h of practice on digit-span and increased his digit-span from 8 to 104 digits. This study assessed changes in the structure of his memory skill after around 30 years of essentially no practice on the digit-span task. On the first day of testing, his estimated span was only 10 digits, but over the following 3 days of testing it increased to 19 digits. Further analyses of his recall performance and verbal reports identified which mechanisms of the original memory skill he could retrieve or reacquire over the 3 days of practice. We discuss theoretical implications for the retention of skilled memory performance, the effects of age-related changes in memory on it, and for the future study of the effects of disuse on exceptional performance and complex skill.



http://ift.tt/2zw2xMO

Pseudoprogression as an adverse event of glioblastoma therapy

Abstract

We explored predictive factors of pseudoprogression (PsP) and its impact on prognosis in a retrospective series of uniformly treated glioblastoma patients. Patients were classified as having PsP, early progression (eP) or neither (nP). We examined potential associations with clinical, molecular, and basal imaging characteristics and compared overall survival (OS), progression-free survival (PFS), post-progression survival (PPS) as well as the relationship between PFS and PPS in the three groups. Of the 256 patients studied, 56 (21.9%) were classified as PsP, 70 (27.3%) as eP, and 130 (50.8%) as nP. Only MGMT methylation status was associated to PsP. MGMT methylated patients had a 3.5-fold greater possibility of having PsP than eP (OR: 3.48; 95% CI: 1.606–7.564; = 0.002). OS was longer for PsP than eP patients (18.9 vs. 12.3 months; = 0.0001) but was similar for PsP and nP patients (= 0.91). OS was shorter–though not significantly so—for PsP than nP patients (OS: 19.5 vs. 27.9 months; = 0.63) in methylated patients. PPS was similar for patients having PsP, eP or nP (PPS: 7.2 vs. 5.4 vs. 6.7; = 0.43). Neurological deterioration occurred in 64.3% of cases at the time they were classified as PsP and in 72.8% of cases of eP (= 0.14). PsP confounds the evaluation of disease and does not confer a survival advantage in glioblastoma.

Thumbnail image of graphical abstract

We explored clinical, molecular and imaging (MRI) predictive factors of pseudoprogression (PsP) in 256 glioblastoma patients. MGMT methylation was the only factor associated with PsP and PsP did not improve OS over nP (neither PsP nor early progression), suggesting that it should be considered an adverse event of therapy and should be reported as such in clinical trials.



http://ift.tt/2hb7pPw

A review of mirvetuximab soravtansine in the treatment of platinum-resistant ovarian cancer

Future Oncology, Ahead of Print.


http://ift.tt/2ytsbBw

Current and Future Treatments for Lysosomal Storage Disorders

Abstract

Purpose of review Lysosomal storage disorders (LSDs) are a class of genetic disorders that are a testing ground for the invention of novel therapeutics including enzyme replacement therapy (ERT), substrate reduction therapy (SRT), gene therapy, and hematopoietic stem cell transplant (HSCT). This review summarizes recently approved drugs, then examines the successful clinical trials in gene therapy and HSCT.

Recent findings The FDA has recently approved a second SRT by reversing an earlier FDA decision, suggesting a favorable regulatory landscape going forward. Adeno-associated virus therapies, adenovirus therapies, and HSCT have overcome limitations of earlier clinical and preclinical trials, suggesting that gene therapy may be a reality for LSDs in the near future. At the same time, the first EU-approved gene therapy drug, Glybera, has been discontinued, and other ex vivo-based therapies although approved for clinical use have failed to be widely adapted and are no longer economically viable.

Summary There are now 11 ERTs and two SRTs approved for LSDs in the USA. Gene therapy approaches and HSCT have also demonstrated promising clinical trial results suggesting that these therapies are on the frontier. Challenges that remain include navigating immune responses, developing drugs capable of crossing the blood-brain barrier (BBB), developing therapies that can reverse end-organ damage, and achieving these goals in a safe, ethical, and financially sustainable manner. The amount of active development and a track record of iterative progress suggest that treatments for LSDs will continue to be a field of innovation, problem solving, and success.



http://ift.tt/2hDvKuE

Sudden death due to malignant hyperthermia with a mutation of RYR1: autopsy, morphology and genetic analysis

Abstract

Malignant hyperthermia (MH) is an autosomal dominant disorder characterized by abnormal calcium homeostasis in skeletal muscles in response to triggering agents. Autopsy, morphology, and genetic analysis were performed on a 19-year-old man who died rapidly after exposure to sevoflurane during maxillofacial surgery. Muscle spasm around the operation area and limb rigidity occurred and renal tubules full of myoglobin casts were observed by microscopy. Ultrastructural changes in the skeletal muscles and the myocardium were detected by transmission electron microscopy (TEM). Genetic analysis disclosed a ryanodine receptor type 1 (RYR1) gene mutation and a nucleoide mutation in chromosome 19q (G1021A) in the deceased and his father. According to the fore mentioned results, the relationship between the cause of death and MH was confirmed. Thus, genetic analysis can be an important procedure in diagnosing MH.



http://ift.tt/2yu7dm6

Hypothalamic-pituitary-adrenal axis variants and childhood trauma influence anxiety sensitivity in South African adolescents

Abstract

Anxiety sensitivity (AS) is characterised by the fear of anxiety-related symptoms and is a risk factor for the development of anxiety-related disorders. We examined whether genetic variation in three stress response genes, CRHR1, NR3C1, and FKBP5, interact with childhood trauma (CT) to predict AS in South African adolescents. Xhosa (n = 634) and Coloured (n = 317) students completed self-report measures of AS and CT, and a total of eighteen polymorphisms within CRHR1, NR3C1, and FKBP5 were genotyped. Differences in AS based on genetic variation and CT were analysed within population and gender groups using multiple linear regression. Associations were found between AS and FKBP5 rs9296158 (p = 0.025) and rs737054 (p = 0.045) in Coloured males. Analysis of gene x CT interactions indicated that NR3C1 rs190488 CC-genotype, NR3C1 rs10482605 G-allele addition, and FKBP5 rs3800373 C-allele addition protect against AS with increasing CT in Xhosa females (p = 0.009), Xhosa males (p = 0.036) and Coloured males (p = 0.049), respectively. We identified two different protective single nucleotide polymorphism (SNP) combinations in a four-SNP CRHR1 haplotype in Coloured males. An analysis of the interaction between CT and a six-SNP FKBP5 haplotype in Coloured males revealed both protective and risk allelic combinations. Our results provide evidence for the influence of both genetic variation in CRHR1, NR3C1 and FKBP5, as well as CT x SNP interactions, on AS in South African adolescents. This study reinforces the importance of examining the influence of gene-environment (G X E) interactions within gender and population groups.



http://ift.tt/2zcNiI2

Integrated 18 F-FDG PET/MRI in breast cancer: early prediction of response to neoadjuvant chemotherapy

Abstract

Purpose

To explore whether integrated 18F-FDG PET/MRI can be used to predict pathological response to neoadjuvant chemotherapy (NAC) in patients with breast cancer.

Methods

Between November 2014 and April 2016, 26 patients with breast cancer who had received NAC and subsequent surgery were prospectively enrolled. Each patient underwent 18F-FDG PET/MRI examination before and after the first cycle of NAC. Qualitative MRI parameters, including morphological descriptors and the presence of peritumoral oedema were assessed. Quantitatively, PET parameters, including maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis (TLG), and MRI parameters, including washout proportion and signal enhancement ratio (SER), were measured. The performance of the imaging parameters singly and in combination in predicting a pathological incomplete response (non-pCR) was assessed.

Results

Of the 26 patients, 7 (26.9%) exhibited a pathological complete response (pCR), and 19 (73.1%) exhibited a non-pCR. No significant differences were found between the pCR and non-pCR groups in the qualitative MRI parameters. The mean percentage reductions in TLG30% on PET and SER on MRI were significantly greater in the pCR group than in the non-pCR group (TLG30% −64.8 ± 15.5% vs. −25.4 ± 48.7%, P = 0.005; SER −34.6 ± 19.7% vs. −8.7 ± 29.0%, P = 0.040). The area under the receiver operating characteristic curve for the percentage change in TLG30% (0.789, 95% CI 0.614 to 0.965) was similar to that for the percentage change in SER (0.789, 95% CI 0.552 to 1.000; P = 1.000).The specificity of TLG30% in predicting pCR) was 100% (7/7) and that of SER was 71.4% (5/7). The sensitivity of TLG30% in predicting non-pCR was 63.2% (12/19) and that of SER was 84.2% (16/19). When the combined TLG30% and SER criterion was applied, sensitivity was 100% (19/19), and specificity was 71.4% (5/7).

Conclusion

18F-FDG PET/MRI can be used to predict non-pCR after the first cycle of NAC in patients with breast cancer and has the potential to improve sensitivity by the addition of MRI parameters to the PET parameters.



http://ift.tt/2A5VUN6

EANM Springer Prizes awarded at EANM’ 17 Vienna



http://ift.tt/2hENjdD

68 Ga-PSMA-11 PET/CT in primary staging of prostate carcinoma: preliminary results on differences between black and white South-Africans

Abstract

Purpose

The incidence of prostate cancer is 60% higher and the mortality rate is two- to three-times greater in black versus white men. We report on differences in 68Ga-PSMA-11 PET/CT imaging findings in 77 black South-African (BSAs) and 18 white South-African (WSAs) treatment-naïve primary prostate carcinoma (PPC) patients.

Methods

68Ga-PSMA-11 PET/CT imaging findings were compared to histological, biochemical and morphological imaging data. Patients were grouped into three Gleason grade groups (GG), GG 1 (scores 3 + 3 and 3 + 4), GG2 (scores 4 + 3 and 4 + 4) and GG3 (scores 9 and 10), and the PSA difference among the groups was determined. Inter-racial difference in SUVmax of the primary tumor as well as its correlation with serum PSA were also determined.

Results

Ninety-three out of 95 PPC where readily identified on 68Ga-PSMA-11 PET/CT imaging. Median PPC SUVmax and serum PSA values proved significantly higher (p = 0.033 and p = 0.003) in GG3 patients (median 16.4 and 180 ng/ml) when compared to GG1 patients (median 9.6 and 25.1 ng/ml) or GG2 patients (median 8.8 and 46.2 ng/ml). SUVmax significantly correlated with serum PSA-values (r = 0.377 (p = 0.0001)). Age, frequency of lymph node involvement and distant metastases, and GGs (p ≥ 0.153) were similar in BSAs and WSAs, both median serum PSA-values as well as SUVmax values proved significantly higher in BSAs when compared to WSAs, respectively, 81.6 ng/ml versus 14.5 ng/ml (p = 0.0001) and 11.9 versus 4.38 (p = 0.004). Moreover, Gleason-score normalized median SUVmax values proved 2.5 times higher in BSAs when compared to WSAs (p = 0.005).

Conclusion

SUVmax values proved significantly related to GG and to be significantly higher in BSAs when compared to WSAs. Also, SUVmax significantly correlated with serum PSA values, which was significantly higher in BSAs when compared with WSAs.



http://ift.tt/2A5USkd

Four-dimensional map of the human early visual system

Humans manage to live under the sun, and are repeatedly exposed to gross and extensive changes in low-level visual information in daily life. For example, you might remember that the sunlight dazzled your eyes when you stepped out from a movie theater. Experimental studies using visual-evoked potentials (VEP) and electrical stimulation suggest that such visual perception is associated primarily with neural processing in the medial-occipital region (Barett et al., 1976; Ducati et al., 1988; Winawer and Parvizi, 2016; Bosking et al., 2017).

http://ift.tt/2zc3zKD

Physician Decision-Making in the Setting of Advanced Illness: An Examination of Patient Disposition and Physician Religiousness

Little is known about patient and physician factors that affect decisions to pursue more or less aggressive treatment courses for patients with advanced illness.

http://ift.tt/2zu0vfS

Visual and Automated Computer Analysis Differ Substantially in Detection of Acidic Reflux in MII-pH Monitoring



http://ift.tt/2h27TDS

CDK4/6 Inhibition Augments Anti-Tumor Immunity by Enhancing T Cell Activation [Research Articles]

Immune checkpoint blockade, exemplified by antibodies targeting the programmed death-1 (PD-1) receptor, can induce durable tumor regressions in some patients. To enhance the efficacy of existing immunotherapies, we screened for small molecules capable of increasing the activity of T cells suppressed by PD-1. Here, we show that short-term exposure to small molecule inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) significantly enhances T cell activation, contributing to anti-tumor effects in vivo, due in part to de-repression of Nuclear Factor of Activated T cell (NFAT) family proteins and their target genes, critical regulators of T cell function. Although CDK4/6 inhibitors decrease T cell proliferation, they increase tumor infiltration and activation of effector T cells. Moreover, CDK4/6 inhibition augments the response to PD-1 blockade in a novel ex vivo organotypic tumor spheroid culture system and in multiple in vivo murine syngeneic models, thereby providing a rationale for combining CDK4/6 inhibitors and immunotherapies.



http://ift.tt/2zw3TH1

Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids [Research Articles]

Ex vivo systems that incorporate features of the tumor microenvironment (TME) and model the dynamic response to immune checkpoint blockade (ICB) may facilitate efforts in precision immuno-oncology and the development of effective combination therapies. Here, we demonstrate the ability to interrogate ex vivo response to ICB using murine- and patient-derived organotypic tumor spheroids (MDOTS/PDOTS). MDOTS/PDOTS isolated from mouse and human tumors retain autologous lymphoid and myeloid cell populations, and respond to ICB in short-term 3-dimensional microfluidic culture. Response and resistance to ICB was recapitulated using MDOTS derived from established immunocompetent mouse tumor models. MDOTS profiling demonstrated that TBK1/IKK inhibition enhanced response to PD-1 blockade, which effectively predicted tumor response in vivo. Systematic profiling of secreted cytokines in PDOTS captured key features associated with response and resistance to PD-1 blockade. Thus, MDOTS/PDOTS profiling represents a novel platform to evaluate ICB using established murine models as well as clinically relevant patient specimens.



http://ift.tt/2zhs0Zj

H3.3K27M Expression Combined with Trp53 Loss Induces High-Grade Glioma [Research Watch]

In utero expression of H3.3K27M with Trp53 loss in mice recapitulates human pediatric high-grade glioma.



http://ift.tt/2zgdktn

The MHC I Genotype Influences Early Driver Events in Cancer [Research Watch]

The incidence of recurrent oncogenic alterations in a tumor is influenced by the MHC I genotype.



http://ift.tt/2zuYkZt

Lorlatinib in ALK+ NSCLC: Robust Phase II Efficacy Seen [News in Brief]

Investigational drug is well tolerated, induces confirmed responses across five cohorts.



http://ift.tt/2zhgnBs

Mutation Load Offers Predictive Biomarker in SCLC [News in Brief]

High number of genomic aberrations linked to better outcomes with checkpoint inhibitors.



http://ift.tt/2zwhK0i

Outcomes of per-oral endoscopic myotomy for treatment of esophageal achalasia with a median follow-up of 49 months

Per-oral endoscopic myotomy (POEM) has received wide acceptance as a highly effective and safe treatment for esophageal achalasia. Short-term and small-scale studies are ample but long-term large-scale studies are few. The aim of the study was to systematically analyze our long-term results of POEM, with particular emphasis on POEM failures and associated risk factors.

http://ift.tt/2zj14rV

Prediction of clinical outcomes in Crohn’s disease by using confocal laser endomicroscopy: results from a prospective multicenter study.

Assessment of prognostic factors in Crohn's disease (CD) patients is of pivotal importance for early intervention and "treat-to-target" strategies. Confocal Laser Endomicroscopy (CLE) enables on demand in vivo characterization of mucosal inflammatory and architectural changes during endoscopy. We prospectively assessed the value of CLE for prediction of clinical outcome parameters in CD.

http://ift.tt/2zv80TY

A novel device for improving visualization in an inadequately prepared colon

Adequate bowel preparation is essential for a quality colonoscopy. Poor bowel preparation can result in longer procedural times, missed adenomas, earlier repeat procedures, increase costs, and decreased patient satisfaction [1-5].Pure-Vu (MOTUS GI, Tirat Carmel, Israel) is a system that facilitates intra-procedural cleaning of a poorly prepared colon during a colonoscopy by irrigating the colon and evacuating the fluid and feces. The study aims were to evaluate Pure-Vu's cleansing capabilities and its usability and safety, in a live animal colon

http://ift.tt/2zhJAw9

Volume of surgery for benign colorectal polyps in the last 11 years

Traditionally large complex colorectal polyps were managed by surgical resection (SR) and in recent years endoscopic resection (ER) has progressed significantly. However, to what extent ER has replaced SR remains largely unknown. We performed a multicenter retrospective cohort study to assess the volume and volume changes of SR for benign colorectal polyps over the past decade.

http://ift.tt/2zvQ6Ae

Radiofrequency ablation combined with biliary stent placement versus stent placement alone for malignant biliary strictures: a systematic review and meta-analysis

Unresectable malignant biliary strictures are generally managed by palliative stent placement for drainage of biliary tree. Recently, radiofrequency ablation (RFA) has been used to improve the patency of biliary stents in these patients. Several studies have evaluated the effectiveness of biliary stent placement with RFA on stent patency and patient survival with variable results. We performed this meta-analysis to evaluate the efficacy and safety of biliary stent placement with RFA compared with stent placement alone in patients with malignant biliary strictures.

http://ift.tt/2zigpcC

Eosinophilic gastritis with involvement of esophageal gastric inlet patch



http://ift.tt/2zv1ahf

Transoral outlet reduction: a comparison of pursestring to interrupted stitch technique

Weight regain after Roux-en-Y gastric bypass (RYGB) correlates with dilated gastrojejunal anastomosis (GJA). Endoscopic sutured transoral outlet reduction (TORe) is safe and effective in the management, and has predominantly been performed by either (1) placing interrupted sutures at the GJA or (2) the creation of a pursestring. The aim of the current study was to compare these techniques.

http://ift.tt/2ziW8nd

Can Echocardiography Be Used to Diagnose Pulmonary Embolism at the Bedside?

The search strategy yielded 5,905 potential references, of which 24 full-text articles were included in the final analysis; pulmonary embolism prevalence was 40.8%. Study design was prospective in 17 studies and retrospective in 7. Risk of bias was low in 7 studies, high in 4, and unclear in the remaining 13. Echocardiograms were performed by physicians in 9 studies (3 by emergency physicians, 5 by cardiologists, and 1 unclear) and at the point of care in 7 studies; 7 studies were conducted solely in the ED.

http://ift.tt/2yuhdeU

Should Buprenorphine Be Administered to Patients With Opioid Withdrawal in the Emergency Department?

Of 3,573 studies identified, 27 met all inclusion criteria for meta-analysis: 6 studies evaluated buprenorphine versus tapered methadone, 7 evaluated tapering buprenorphine, and 14 evaluated buprenorphine versus α2-adrenergic agonists (primarily clonidine).

http://ift.tt/2lORA2A

What Is the Diagnostic Performance of Ultrasonography to Diagnose Small Bowel Obstruction?

Authors included 11 prospective, observational studies for analysis, with 1,178 patients, from an initial 9,545 identified studies (after removal of duplicates) (Table). Study setting was the emergency department (ED) for 5 studies, whereas for the remaining 6 studies it was either non-ED or not specified. Studies were conducted in 10 countries. Reference standards varied, including surgical examination, CT, colonoscopy, enema, enteroclysis, pathology, and clinical follow-up. Seven studies did not specify the training protocol or ultrasonographic experience of the study ultrasonographers; the remaining studies generally reported a combination of didactic training focused on the ultrasonographic diagnosis of small bowel obstruction and previous ultrasonographic practical experience spanning several ultrasonographic studies or greater than 2 years of regular ultrasonographic experience.

http://ift.tt/2yt48mc

Transgender and Gender-Nonconforming Patients in the Emergency Department: What Physicians Know, Think, and Do

We explore self-reported knowledge, attitudes, and behaviors of emergency physicians in regard to the care of transgender and gender-nonconforming patients to identify opportunities to improve care of this population.

http://ift.tt/2lOHyi9

Functional Role of A Novel Long Noncoding RNA TTN-AS1 in Esophageal Squamous Cell Carcinoma Progression and Metastasis

Purpose: Emerging studies demonstrate that long non-coding RNAs (lncRNAs)participate in the regulation of various cancers. In the current study, a novel lncRNA-TTN-AS1 has been identified and explored in esophageal squamous cell carcinoma (ESCC). Experimental Design: To discover a new regulatory circuitry in which RNAs crosstalk with each other, the transcriptome of lncRNA-miRNA-mRNA from ESCC and adjacent non-malignant specimens were analyzed using multiple microarrays and diverse bioinformatics platforms. The functional role and mechanism of a novel lncRNA-TTN-AS1 were further investigated by gain-of and loss-off function assays in vivo and in vitro. An ESCC biomarker panel, consisting of lncRNA-TTN-AS1, miR-133b and FSCN1, was validated by qRT-RCP and in situ hybridization using samples from 148 patients. Results: LncRNA-TN-AS1 as an oncogene, is highly expressed in ESCC tissues and cell lines, and promotes ESCC cell proliferation and metastasis. Mechanistically, lncRNA-TTN-AS1 promotes expression of transcription factor Snail1 by competitively binding miR-133b, resulting in the epithelial-mesenchymal transition (EMT) cascade. Moreover, lncRNA-TTN-AS1 also induces FSCN1 expression by sponging miR-133b and upregulation of mRNA stabilizing protein HuR, which further promotes ESCC invasion cascades. We also discovered and validated a clinically applicable ESCC biomarker panel, consisting of lncRNA-TTN-AS1, miR-133b and FSCN1, that is significantly associated with overall survival and provides additional prognostic evidence for ESCC patients. Conclusions: As a novel regulator, lncRNA-TTN-AS1 plays an important role in ESCC cell proliferation and metastasis. The lncRNA-TTN-AS1/miR133b/FSCN1 regulatory axis provides bona fide targets for anti-ESCC therapies.



http://ift.tt/2zwqhjJ

Pancreatic Ductal Adenocarcinoma Subtyping using the Biomarkers Hepatocyte Nuclear Factor-1A and Cytokeratin-81 Correlates with Outcome and Treatment Response.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is associated with a dismal prognosis and poor therapeutic response to current chemotherapy regimens in unselected patient populations. Recently, it has been shown that PDAC may be stratified into functionally and therapeutically relevant molecular subgroups and that some of these subtypes can be recapitulated by immunohistochemistry for KRT81 (QM/squamous/basal like) and HNF1A (non-QM, overlap with exocrine/ADEX subtype). Experimental Design: We validated the different outcome of the HNF1A / KRT81 PDAC subtypes in two independent cohorts of surgically treated patients and examined the treatment response to chemotherapy in a third cohort of unresectable patients. The first two cohorts included 262 and 130 patients, respectively, and the third independent cohort comprised advanced-stage PDAC patients who were either treated with FOLFIRINOX (64 patients) or Gemcitabine (61 patients). Results: In both cohorts with resected PDAC the HNF1A-positive subtype showed the best, the KRT81-positive subtype the worst and the double negative subtype an intermediate survival (p <0.013 and <0.009, respectively). In the chemotherapy cohort the survival difference between the double negative and the HNF1A-positive subtype was lost, while the dismal prognosis of KRT81-positive PDAC patients was retained (p <0.021). Patients with a KRT81-positive subtype did not benefit from FOLFIRINOX-therapy, while those with HNF1A-positive tumors responded better compared to Gemcitabine-based treatment (p <0.038). Conclusions: Immunohistochemical stratification recapitulating molecular subtypes of PDAC using HNF1A and KRT81 is associated with significantly differing outcomes and responses to chemotherapy. These results may pave the way towards future pretherapeutic biomarker based stratification of PDAC patients.



http://ift.tt/2zhsjTL

Comments on Gabbani, et al. Metabolomic analysis with 1H NMR for non-invasive diagnosis of hepatic fibrosis degree in patients with chronic hepatitis C



http://ift.tt/2lOrVqW

Does Azathioprine induce endoscopic and histologic healing in Pediatric Inflammatory Bowel Disease? A prospective, observational study

The new concept of disease remission for pediatric inflammatory bowel diseases (IBD) implies the achievement of mucosal healing.

http://ift.tt/2ysFT7P

Simultaneous Integrated Boost for Radiation Dose Escalation to the Gross Tumor Volume with Intensity-Modulated (Photon) Radiation Therapy or Intensity-Modulated Proton Therapy and Concurrent Chemotherapy for Stage II-III Non-Small Cell Lung Cancer: A Phase I Study

Local failure is common after conventionally fractionated, standard-dose chemoradiation for NSCLC. Theoretically, higher doses could confer a survival benefit, but this has not been confirmed in a phase III trial using conventional techniques. Dose escalation by new strategies seems promising. Our study is trying to find the optimal dose and fractionation by image-guided IMRT or IMPT with a simultaneous integrated boost. This article presents our preliminary results of a phase I study.Simultaneous Integrated Boost for Radiation Dose Escalation to the Gross Tumor Volume with Intensity-Modulated (Photon) Radiation Therapy or Intensity-Modulated Proton Therapy and Concurrent Chemotherapy for Stage II-III Non-Small Cell Lung Cancer: A Phase I Study

http://ift.tt/2hCMBO4

Gray Zone Coping with Knife: Post-operative Management of Nodular Lymphocyte Predominant Hodgkin Lymphoma



http://ift.tt/2A7etAS

Optimal high dose rate brachytherapy fractionation scheme after keloid excision. A retrospective multicenter comparison of recurrence rates and complications

Keloid treatment with excision followed by brachytherapy is considered the most effective. However, the optimal fractionation scheme is unknown. Patient cohorts from three centers using 2x9 Gy, 3x6 Gy, or 2x6 Gy were analyzed. The scheme using 2x6 Gy had equally low recurrence and lower complication rates, showing a BED of 20 Gy is adequate in post-excisional HDR brachytherapy keloid treatment.

http://ift.tt/2hDAobS

Posttraumatic stress-related psychological functioning in adult survivors of childhood cancer

Abstract

Purpose

The majority of research examining posttraumatic stress symptoms/disorder (PTSS/PTSD) among adult survivors of childhood cancer has been oriented to cancer, assuming that cancer has been the most traumatic experience in their lives. Whether that assumption is valid, and how it might impact assessment of PTSS, is unknown.

Methods

Survivors in the St. Jude Lifetime Cohort study completed an assessment of PTSS without cancer orientation, global psychological functioning, perceived stress, and cancer-related anxiety.

Results

Participants (n = 2969; Mage = 32.5 ± 8.5 years, 24.1 years since diagnosis, 49.1% female) obtained a mean score on the PTSD Checklist of 27.7, which is comparable to a normative population. Using established cutoffs, 11.8% obtained scores in the at-risk range. Multivariable modeling indicated that psychological factors [global distress (p < 0.0001), perceived stress (p = 0.001), cancer-related anxiety (p < 0.0001)] and demographic variables [female gender (p < 0.0001), survivors with less than a college education (p = 0.002)] were risk factors for increased PTSS. Only 14.5% identified a cancer-related traumatic event, and there was no difference in PTSS scores between those who identified cancer vs. non-cancer events as most stressful (28.4 ± 12.6 vs. 28.5 ± 12.7, p = 0.93).

Conclusion

One in eight adult long-term survivors of childhood cancer had PTSS above the cutoff, though subgroups (e.g., females and those with lower education) report more distress symptoms. Most adult survivors do not identify cancer as their most stressful event.

Implications for cancer survivors

Screening for distress in survivorship clinics should not assume that distress is directly related to the survivor's cancer experience.



http://ift.tt/2ytjsza

A systematic review and diagnostic test accuracy meta-analysis of the validity of anion gap as a screening tool for hyperlactatemia

This systematic review and meta-analysis seeks to determine the validity of the anion gap to screen for hyperlactatemia in critically ill patients. We have previously shown that the anion gap does not predict ...

http://ift.tt/2A62bsk

Vaccine-related poliovirus shedding in trivalent polio vaccine and human immunodeficiency virus status: analysis from under five children

Poliomyelitis is an acute viral infection caused by poliovirus and transmitted via the fecal–oral route. The causative agent is one of the three serotypes of poliovirus (serotypes 1, 2, 3) that differ slightly...

http://ift.tt/2hCReru

Garcinia mangostana Linn displays antidepressant-like and pro-cognitive effects in a genetic animal model of depression: a bio-behavioral study in the Flinders Sensitive Line rat

Abstract

There is abundant evidence for both disorganized redox balance and cognitive deficits in major depressive disorder (MDD). Garcinia mangostana Linn (GM) has anti-oxidant activity. We studied the antidepressant-like and pro-cognitive effects of raw GM rind in Flinders Sensitive Line (FSL) rats, a genetic model of depression, following acute and chronic treatment compared to a reference antidepressant, imipramine (IMI). The chemical composition of the GM extract was analysed for levels of α- and γ-mangostin. The acute dose-dependent effects of GM (50, 150 and 200 mg/kg po), IMI (20 mg/kg po) and vehicle were determined in the forced swim test (FST) in FSL rats, versus Flinders Resistant Line (FRL) control rats. Locomotor testing was conducted using the open field test (OFT). Using the most effective dose above coupled with behavioral testing in the FST and cognitive assessment in the novel object recognition test (nORT), a fixed dose 14-day treatment study of GM was performed and compared to IMI- (20 mg/kg/day) and vehicle-treated animals. Chronic treated animals were also assessed with respect to frontal cortex and hippocampal monoamine levels and accumulation of malondialdehyde. FSL rats showed significant cognitive deficits and depressive-like behavior, with disordered cortico-hippocampal 5-hydroxyindole acetic acid (5-HIAA) and noradrenaline (NA), as well as elevated hippocampal lipid peroxidation. Acute and chronic IMI treatment evoked pronounced antidepressant-like effects. Raw GM extract contained 117 mg/g and 11 mg/g α- and γ-mangostin, respectively, with acute GM demonstrating antidepressant-like effects at 50 mg/kg/day. Chronic GM (50 mg/kg/d) displayed significant antidepressant- and pro-cognitive effects, while demonstrating parity with IMI. Both behavioral and monoamine assessments suggest a more prominent serotonergic action for GM as opposed to a noradrenergic action for IMI, while both IMI and GM reversed hippocampal lipid peroxidation in FSL animals. Concluding, FSL rats present with cognitive deficits and depressive-like behaviors that are reversed by acute and chronic GM treatment, similar to that of IMI.



http://ift.tt/2A4Y8N2

Learning With E-books and Project-based Strategy in a Community Health Nursing Course.

With advances in information technology, "information-assisted instruction" has been gradually introduced to nursing education curricula. Specifically, the integration of an e-book system can effectively enhance nursing students' attention and interest. Most studies on nursing education that incorporated e-books have focused on the advantages of convenience and assistance provided by e-books. Few studies have addressed community health nursing and off-campus practice activities in relation to suitable teaching strategies for learning activities. This study involved designing and planning a multimedia e-book learning system with a project-based learning activity that conforms to the curriculum and practical requirements of a community health nursing course. The purpose was to reduce the gap between theory and practice and realize an effective learning process. For learning evaluations, a final examination analysis with an independent sample t test; a scoring scheme with intrateam, interteam, and expert ratings; and Bloom's taxonomy-based analysis were conducted. The evaluation results indicated that the comprehension and learning abilities of the experimental group using the e-book system with a mobile device were effectively improved. In addition, the exploratory process involved in project-based learning can develop multiple cognitive skills and problem-solving ability, thereby realizing effective learning. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2xXA0eB

Clinical Implications of NRAS Overexpression in Resectable Pancreatic Adenocarcinoma Patients

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer, and its incidence is rising worldwide. Although survival can be improved by surgical resection, when detected at an early stage, this type of cancer is usually asymptomatic, and disease becomes only apparent after metastasis. Adjuvant treatment does not improve survival, thus after surgery there is a lack of predictive and prognosis biomarkers to predict treatment response and survival. The mitogen-activated protein-kinase and phosphoinositide 3-kinase signalling pathways play a crucial role in cancer development and progression. Especially, activated RAS proteins promote cell proliferation through constitutive stimulation of the downstream effectors RAF-MEK-ERK and PI3K-AKT. Mutational status of NRAS is required in several types of cancer like colorectal or cutaneous melanoma. However, mutations in this gene are very scarce in PDAC patients, and NRAS determination is not usually performed in clinical practice for this kind of tumor. In this study, we analyse the association between NRAS protein expression and progression-free survival and overall survival of an homogenous cohort of pancreatic ductal adenocarcinoma patients from a single-centre. Interestingly, we found that patients with high expression not only showed longer progression-free survival than those patients with low expression (22 versus 9 months, respectively) (P = 0.013), but also longer overall survival (43 versus 19 months, respectively) (P = 0.020). These results confirm NRAS expression could be used to differentiate patients according to their prognosis. Proportional hazard model revealed NRAS expression together with grade of differentiation as pathological variables to predict patient's outcome.



http://ift.tt/2zdfeca

Tumor Biology Predicts Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients Presenting with Locally Advanced Breast Cancer

Abstract

Background

Neoadjuvant chemotherapy (NAC) is used to convert patients with inoperable locally advanced breast cancer (LABC) to operability, but has not traditionally been used to avoid mastectomy or axillary dissection in this subset.

Objective

The purpose of this study was to determine the rates of pathologic complete response (pCR) in LABC patients, and identify factors predictive of pCR to determine if responding patients might be suitable for limited surgery.

Methods

From 2006 to 2016, 1522 patients received NAC followed by surgery; 321 had advanced disease in the breast (cT4) and/or in the nodes (cN2/N3). pCR rates were assessed by T and N stage, and receptor subtype.

Results

Of 321 LABC patients, 223 were cT4, 77 were cN2, and 82 were cN3. Forty-three percent were hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative (HR+/HER2−), 23% were triple negative, and 34% were HER2+. The overall pCR rate was 25% and differed by receptor subtype (HR+/HER2− 7%, triple negative 23%, HER2+ 48%; p < 0.001). Breast pCR occurred in 27% of patients and was similar in T4 versus non-T4 disease (29% vs. 22%; p = 0.26). Nodal pCR was achieved in 38% of cN+ patients and did not differ by nodal stage (cN1 43%, cN2 36%, cN3 32%; p = 0.23). Nodal pCR was significantly more common than breast pCR (p = 0.014) across all tumor subtypes. Receptor subtype was the only predictor of overall pCR (p < 0.001).

Conclusion

In patients with LABC, pCR after NAC was seen in 25%, and did not differ by T or N stage. Tumor biology, but not extent of disease, predicted pCR. Studies assessing the feasibility of surgical downstaging with NAC in LABC patients are warranted.



http://ift.tt/2A4o0IU

Expression of 3β-Hydroxysteroid Dehydrogenase Type 1 in Breast Cancer is Associated with Poor Prognosis Independent of Estrogen Receptor Status

Abstract

Background

Human 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) plays a vital role in steroidogenesis in breast tumors and may therefore be a suitable target for treatment of breast cancer. This study investigated the role of HSD3B1 in the pathogenesis of breast cancer in clinical and experimental settings.

Methods

Expression of HSD3B1 in primary tumors of 258 breast cancer patients was evaluated by immunohistochemistry. Screening of breast cancer cell lines indicated that triple-negative MDA-MB-231 cells expressed HSD3B1. The effects from genetic and pharmacologic inhibition of HSD3B1 were assessed in vitro and in vivo.

Results

The findings showed that 44% of the 258 breast cancers were HSD3B1-positive. The HSD3B1-positivity was associated with advanced-stage disease (p = 0.009) and reduced recurrence-free survival (p = 0.048) but not with tumor subtype or estrogen receptor status. Silencing of HSD3B1 or treatment with an HSD3B1 inhibitor (trilostane) reduced colony formation in breast cancer cells. Knockdown of HSD3B1 inhibited cell proliferation and migration. Analysis of a murine xenograft tumor model indicated that trilostane significantly slowed tumor growth.

Conclusions

Expression of HSD3B1 in breast cancer is negatively associated with prognosis. The study found HSD3B1 to be a potential therapeutic target for breast cancer independent of estrogen receptor status.



http://ift.tt/2hCpDqb

High STMN1 Expression is Associated with Cancer Progression and Chemo-Resistance in Lung Squamous Cell Carcinoma

Abstract

Background

Known as a microtubule-destabilizing protein, STMN1 (gene symbol: STMN1) regulates the dynamics of microtubules, cell cycle progress, and chemo-resistance against taxane agents. It is highly expressed in various human cancers and involved in cancer progression as well as poor prognosis.

Methods

Expression of STMN1 was examined by immunohistochemistry using FFPE tissue sections from 186 patients with lung squamous cell carcinoma (LSCC). Analysis of STMN1 suppression was performed for STMN1 small interfering RNA (siRNA)-transfected LSCC cell lines to determine the change in proliferation, invasive and apoptosis abilities, and paclitaxel sensitivity.

Results

The cytoplasmic STMN1 expression in LSCC was higher than in normal tissues. The high expression was significantly associated with vascular invasion (P = 0.0477) and poor prognosis. In addition, the proliferating and invasive abilities were decreased, and the apoptosis ability and paclitaxel sensitivity were increased in STMN1-suppressed LSCC cells compared with control cells.

Conclusion

The results suggest that STMN1 is a prognostic factor that also is associated with caner progression and chemo-resistance. Therefore, STMN1 could be a predictor for poor prognosis and a potential therapeutic target in LSCC.



http://ift.tt/2hDlTVx

Anti-Candida activity of antimicrobial impregnated central venous catheters

Whenever the rate of central line-associated bloodstream infections (CLABSIs) remains high even after the implementation of preventive strategies, the use of chlorhexidine/silver sulfadiazine (CSS) or minocycl...

http://ift.tt/2lNyolJ

Elastic stains in the evaluation of DCIS with comedo necrosis in breast cancers

Abstract

As concerns the microscopic morphology of ductal carcinoma in situ (DCIS), neoplastic cells are surrounded by both a myoepithelial cell layer and a basement membrane as expected from the outer structure of ducts and lobules. However, in some cases, it is impossible to state whether the structures involved by the disease are ducts or lobules. Altogether 1220 anatomic structures involved by DCIS displaying comedo necrosis from 27 slides of 21 patients (seen on both haematoxylin and eosin-stained and orcein-stained slides) were identified as representing ducts, likely ducts, unclassifiable structures, likely acini or acini on the basis of their distribution and resemblance to normal anatomic structures. All structures were then rated as having a circumferential elastic layer (as normal ducts), a partial elastic layer around more or less than half of the periphery or having no peripheral elastic layer at all (as normal acini). Structures classified as ducts or likely ducts were likely to have an elastic coating, whereas acini and likely acini had no such coating. Unclassifiable structures were generally devoid of an elastic layer. Structures (and cases) that were likely to represent neoductgenesis as proposed by Zhou et al. (Int J Breast Cancer 2014;2014:581706) were generally unclassifiable and devoid of outer elastic layer. Many duct-like structures in DCIS with comedo necrosis are devoid of elastic layer typical of normal ducts, suggesting that these structures are abnormal despite conservation of the myoepithelium and the basement membrane.



http://ift.tt/2j223ad

NAAC introduces Certified Ambulance Documentation Specialist (CADS) course

CADS is the nation's first documentation-specific certification course for EMS practitioners and officers HERSHEY, Pa. — Hershey is known for being the sweetest place on earth. But after the five-day abc360 conference at the Hershey Lodge Oct. 21-25, it is also on the map for rolling out the Certified Ambulance Documentation Specialist (CADS) course for the nation's EMS industry. The ...

http://ift.tt/2yranXz

Frontmatter



http://ift.tt/2zcYN2d

Visual assessment of sample quality: quo usque tandem?

Authors: Lippi, Giuseppe / Cadamuro, Janne


http://ift.tt/2xe9ltD

Tumor microenvironment and systemic disease: a dual target in medical oncology (also in the case of biomarkers)

Authors: Melichar, Bohuslav


http://ift.tt/2zaHeiZ

How to reduce scientific irreproducibility: the 5-year reflection

Authors: Fiala, Clare / Diamandis, Eleftherios P.


http://ift.tt/2hadT14

Frontmatter



http://ift.tt/2zcqkAD

The porphyrias: from clinical presentation to a diagnosis. The role of the laboratory profession



http://ift.tt/2hadPym

Closing Lecture



http://ift.tt/2zb2FRf

Risk Management and its utility in the clinical laboratory



http://ift.tt/2hadMTc

Laboratory Reference Intervals: Global Initiatives and Harmonization challenges



http://ift.tt/2zcYBQx

High-sensitivity assays for cardiac troponins – continued

Authors: Lackner, Karl J.


http://ift.tt/2haWPZ6

Terminology of cardiac troponin assays and data censoring

Authors: Jarolim, Petr


http://ift.tt/2zcYyUR

Automated antinuclear immunofluorescence antibody analysis is a reliable approach in routine clinical laboratories

Authors: Zheng, Bing / Li, Enling / Zhu, Haoming / Lu, Jingbo / Shi, Xinming / Zhang, Jie / Li, Min


http://ift.tt/2haWMwo

High-sensitivity cardiac troponin: do think twice, it’s not all right

Authors: Ungerer, Jacobus P.J. / Pretorius, Carel J.


http://ift.tt/2zcYwMJ

Fast track protocols using highly sensitive troponin assays for ruling out and ruling in non-ST elevation acute coronary syndrome

Authors: Ferraro, Simona / Dolci, Alberto / Panteghini, Mauro


http://ift.tt/2haWJ3G

Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in adults with vitamin D insufficiency

Authors: Saleh, Lanja / Tang, Jonathan / Gawinecka, Joanna / Boesch, Lukas / Fraser, William D. / von Eckardstein, Arnold / Nowak, Albina


http://ift.tt/2zcYwfH

Determination of Thermodynamic Properties of Alkaline Earth-liquid Metal Alloys Using the Electromotive Force Technique

56718eq1.jpg

This protocol describes the measurement of the electromotive force of alkaline-earth elements in liquid metal alloys at high temperatures (723-1,123 K) to determine their thermodynamic properties, including activity, partial molar entropy, partial molar enthalpy, and phase transition temperatures, over a wide composition range.

http://ift.tt/2ze7dDR

New Research From Clinical Psychological Science

Read about the latest research from Clinical Psychological Science:

What Drives False Memories in Psychopathology? A Case for Associative Activation

Henry Otgaar, Peter Muris, Mark L. Howe, and Harald Merckelbach

Memories play an influential role in both clinical and legal settings because memory anomalies are characteristic of posttraumatic stress disorder (PTSD) and depression. For example, PTSD has been shown to incorporate poorly elaborated and integrated memories, which may lead to problems with intentional recall, whereas depression has been linked to distinct autobiographical memory problems. Findings from past research on the effects of PTSD and depression on false memory have been inconsistent. The current review examines associative activation as the link between PTSD, depression, and spontaneous false memory. Associative activation theories conceptualize memory as containing representations or nodes that are interconnected by associative links. When information is encoded, activation can spread, triggering related information that may or may not have been part of the original experience. The authors examined the link between psychopathology (i.e., PTSD and depression) and false memories in two meta-analyses. The results indicated that individuals with these two conditions are at a greater risk of generating false memories — but only when exposed to negative or trauma-related material The authors suggest that this type of material may map onto participants' knowledge base, thus allowing them to make rapid linkages to associated information.

Negative Event Recall as a Vulnerability for Depression: Relationship Between Momentary Stress-Reactive Rumination and Memory for Daily Life Stress

Samantha L. Connolly and Lauren B. Alloy

Rumination has been found to predict the onset, duration, and number of depressive episodes people experience. One theory explaining the connection between rumination and depression suggests that rumination leads to deeper encoding of negative stimuli and maintenance of negative stimuli in long-term memory. This in turn leads to increased recall of negative information and depressed mood. The researchers tested this hypothesis by having participants complete assessments of depression, verbal memory, and rumination. Participants then took part in a 7-day ecological momentary assessment (EMA) procedure in which they reported, four times a day, negative life events that had occurred to them since the previous reporting period, along with the intensity of the event. In a follow-up assessment completed after the EMA procedure, participants completed reports of common life events, depression, and verbal memory. Negative events followed by rumination were more likely to be recalled at the 2-week follow-up, and those who recalled more stressors had increased depressive symptoms. Memory for negative life events was not found to mediate the relationship between rumination and depressive symptoms. This study provides preliminary support for the influence of rumination on memory and depressive symptoms.

Improvements in Negative Parenting Mediate Changes in Children's Autonomic Responding Following a Preschool Intervention for ADHD

Ziv Bell, Tiffany Shader, Carolyn Webster-Stratton, M. Jamila Reid, and Theodore P. Beauchaine

Children with externalizing disorders often display abnormal patterns of sympathetic- and parasympathetic-linked cardiac activity and reactivity. Recent research suggests that these patterns of physiological activity may be shaped by coercive family interactions. In this study, the researchers examined whether parenting serves as a mediator for changes in parasympathetic- and sympathetic-nervous system reactivity and activity after treatment for attention-deficit/hyperactivity disorder (ADHD). To examine this, children ages 4 to 6 with ADHD and their parents took part in the Incredible Years intervention. In this intervention, parents attend parenting training and support groups, and children take part in structured and unstructured group activities teaching anger management, emotional regulation, and appropriate social behaviors. Children's respiratory sinus arrhythmia (RSA), cardiac pre-ejection period (PEP), and behavioral interactions with their parent were assessed before and after the intervention. The researchers found that increases in resting RSA and greater PEP reactivity to incentives were mediated, in part, by reductions in negative parenting.

Psychodynamic and Cognitive-Behavioral Therapies Are More Different Than You Think: Conceptualizations of Mental Problems and Consequences for Studying Mechanisms of Change

Asle Hoffart and Sverre Urnes Johnson

Psychodynamic therapy and cognitive behavioral therapy are two interventions commonly used to treat a wide variety of mental-health disorders. In this article, the authors examine whether the kinds of theoretical models that are used to explain mental disorders in these interventions influence the ability to study mechanisms of change. The authors detail how the theories behind these interventions conceptualize social anxiety disorder (SAD); in psychodynamic therapy, it is viewed using an essentialist model, and in cognitive behavioral therapy, it is viewed using a mechanistic property cluster model. The authors then examine how treatment evolves from these conceptualizations and look at whether the mechanisms of change inherent to each intervention can be identified and tested. The authors find, among other things, that the main explanatory mechanism of SAD cannot be dissociated from symptoms in psychodynamic theory, and therefore explanatory mechanisms cannot be adequately tested. In contrast, the conceptualization of SAD in cognitive therapy is one that can be adequately tested. The authors suggest the need to leave essentialist viewpoints behind in favor of mechanistic property cluster models.



http://ift.tt/2hbptsW

Resting regional brain metabolism in social anxiety disorder and the effect of moclobemide therapy

Abstract

While there is mounting evidence of abnormal reactivity of several brain regions in social anxiety disorder, and disrupted functional connectivity between these regions at rest, relatively little is known regarding resting regional neural activity in these structures, or how such activity is affected by pharmacotherapy. Using 2-deoxy-2-(F-18)fluoro-D-glucose positron emission tomography, we compared resting regional brain metabolism between SAD and healthy control groups; and in SAD participants before and after moclobemide therapy. Voxel-based analyses were confined to a predefined search volume. A second, exploratory whole-brain analysis was conducted using a more liberal statistical threshold. Fifteen SAD participants and fifteen matched controls were included in the group comparison. A subgroup of SAD participants (n = 11) was included in the therapy effect comparison. No significant clusters were identified in the primary analysis. In the exploratory analysis, the SAD group exhibited increased metabolism in left fusiform gyrus and right temporal pole. After therapy, SAD participants exhibited reductions in regional metabolism in a medial dorsal prefrontal region and increases in right caudate, right insula and left postcentral gyrus. This study adds to the limited existing work on resting regional brain activity in SAD and the effects of therapy. The negative results of our primary analysis suggest that resting regional activity differences in the disorder, and moclobemide effects on regional metabolism, if present, are small. While the outcomes of our secondary analysis should be interpreted with caution, they may contribute to formulating future hypotheses or in pooled analyses.



http://ift.tt/2haf68I

The anxiolytic-like effects of puerarin are associated with the changes of monoaminergic neurotransmitters and biosynthesis of allopregnanolone in the brain

Abstract

Anxiety disorder is a serious and burdensome psychiatric illness that frequently turn into chronic clinical conditions. Puerarin have been shown to be effective in the therapy of depression. However, few studies are concerned about the anxiolytic-like effects of puerarin. The current study aimed to evaluate the anxiolytic-like effects of puerarin and its possible mechanism. To evaluate this, the behavioral tests, i.e. Vogel-type conflict test (VTCT), elevated plus-maze test (EPMT), and open-field test (OFT) were conducted. Data showed that similar to the positive-control drug sertraline (Ser) (15 mg/kg, i.g.), the anxiolytic-like effects were produced by puerarin (60 and 120 mg/kg, i.g.) in VTCT and EMPT respectively without affecting locomotor activity in OFT. Moreover, the present study also found that consistent with Ser, the levels of allopregnanolone and serotonin (5-HT) in the prefrontal cortex and hippocampus were increased by puerarin (60 and 120 mg/kg, i.g.), respectively. In summary, the present study indicated that puerarin exerted the anxiolytic-like effects, which maybe associated with normalization of 5-HT levels and biosynthesis of allopregnanolone in brain.



http://ift.tt/2zblqns

Normal diet Vs High fat diet - A comparative study: Behavioral and neuroimmunological changes in adolescent male mice.

Abstract

Recent evidence has established that consumption of High-fat diet (HFD)-induced obesity is associated with deficits in hippocampus-dependent memory/learning and mood states. Nevertheless the link between obesity and emotional disorders still remains to be elucidated. This issue is of particular interest during adolescence, which is important period for shaping learning/memory and mood regulation that can be sensitive to the detrimental effects of HFD. Our present study is focused to investigate behavioral and metabolic influences of short–term HFD intake in adolescent C57BL/6 mice. HFD caused weight gain, impaired glucose tolerance (IGT) and depression-like behavior as early as after 3 weeks which was clearly proved by a decrease in number of groomings in the open field test (OFT) and an increase in immobility time in the tail suspension test (TST). In the 4th week HFD induced obese model was fully developed and above behavioral symptoms were more dominant (decrease in number of crossings and groomings and increase in immobility time in both FST and TST). At the end of 6th week hippocampal analysis revealed the differences in morphology (reduced Nissl positive neurons and decreased the 5-HT1A receptor expression), neuronal survival (increased cleaved caspase-3 expression), synaptic plasticity (down regulation of p-CREB and BDNF), and inflammatory responses (increase in expression of pro-inflammatory cytokines and decrease in expression of anti-inflammatory cyokines) in HFD mice. Our results demonstrate that, high-fat feeding of adolescent mice could provoke "depression-like" behavior as early as 3 weeks and modulate structure, neuron survival and neuroinflammation in hippocampus as early as 6 weeks proving that adolescent age is much prone to adverse effects of HFD, which causes obesity, behavioral differences, memory and learning deficiencies.



http://ift.tt/2hakhWs

Antibacterial, antioxidant and Immuno-modulatory properties in extracts of Barleria lupulina Lindl.

Antibacterial, immunomodulatory and antioxidant properties of aerial parts of Barleria lupulina Lindl were investigated in the present communication.

http://ift.tt/2h11SHR

Structure and function of the human parvulins Pin1 and Par14/17

Authors: Matena, Anja / Rehic, Edisa / Hönig, Dana / Kamba, Bianca / Bayer, Peter


http://ift.tt/2iYNP9R

Frontmatter



http://ift.tt/2Aigivx

A novel design of HA-coated nanoparticles co-encapsulating plasmid METase and 5-Fu shows enhanced application in targeting gastric cancer stem cells

Authors: Yanga, Weifeng / Zhanga, Houting / Xin, Lin


http://ift.tt/2iXIfEN

PARP-1 and PARP-2 activity in cancer-induced cachexia: potential therapeutic implications

Authors: Barreiro, Esther / Gea, Joaquim


http://ift.tt/2iZ6mCY

Production of recombinant porin from Y. pseudotuberculosis in a water-soluble form for pseudotuberculosis diagnostics

Authors: Golotin, Vasily / Portnyagina, Olga / Chopenko, Natalia / Kim, Natalia / Rasskazov, Valery / Novikova, Olga


http://ift.tt/2AhazGn

Progress in understanding the molecular oxygen paradox – function of mitochondrial reactive oxygen species in cell signaling

Authors: Kuksal, Nidhi / Chalker, Julia / Mailloux, Ryan J.


http://ift.tt/2iZ68vC

Human U3 protein 14a plays an anti-apoptotic role in cancer cells

Authors: Ma, Teng / Lu, Chenxi / Guo, Yafei / Zhang, Chunfeng / Du, Xiaojuan


http://ift.tt/2Af3ypn

Functional control of polypeptide GalNAc-transferase 3 through an acetylation site in the C-terminal lectin domain

Authors: Lorenz, Virginia / Cejas, Romina B. / Bennett, Eric P. / Nores, Gustavo A. / Irazoqui, Fernando J.


http://ift.tt/2iZboiE

Reactive nitrogen species (RNS)-resistant microbes: adaptation and medical implications

Authors: Tharmalingam, Sujeenthar / Alhasawi, Azhar / Appanna, Varun P. / Lemire, Joe / Appanna, Vasu D.


http://ift.tt/2Af3gyN

Cellular and plasma nitrite levels in myeloid leukemia: a pathogenetic decrease

Authors: Jain, Mili / Kumar, Ashutosh / Singh, Uma Shankar / Kushwaha, Rashmi / Singh, Abhishek Kumar / Dikshit, Madhu / Tripathi, Anil Kumar


http://ift.tt/2j0cZFd

Immune-regulation and -functions of eicosanoid lipid mediators

Authors: Esser-von Bieren, Julia


http://ift.tt/2AjGbeu

Oxidised protein metabolism: recent insights

Authors: Samardzic, Kate / Rodgers, Kenneth J.


http://ift.tt/2j1Tqwl

Immunofluorescence Microscopy of γH2AX and 53BP1 for Analyzing the Formation and Repair of DNA Double-strand Breaks

56617fig1v3.jpg

This manuscript provides a protocol for the analysis of DNA double-strand breaks by immunofluorescence microscopy of γH2AX and 53BP1.

http://ift.tt/2lMeeJb

A qualitative exploration of the experiences, needs, and roles of caregivers during and after cancer treatment: “That’s what I say. I’m a relative survivor”

Abstract

Purpose

The transition out of acute cancer treatment has been identified as a time of stress and uncertainty for cancer survivors, but little is known about how caregivers fare during this period. In this paper, we discuss caregiving work up to and including transition from initial care and the needs of caregivers during transition and beyond.

Methods

We held four focus groups with breast, prostate, and colorectal cancer survivors who had completed treatment with intent to cure and two with caregivers for the same population. Participants were affiliated with either an urban academic or rural community cancer center. The discussions focused on cancer-related experiences and needs during the transition out of acute cancer care.

Results

Focus groups included 47 people: 28 survivors and 19 caregivers. Three key caregiving themes identified the significance of support for the patient in the clinic, support for the patient in the home, and for caregiver self-care.

Conclusions

Discussions revealed aspects of caregiving that created difficulties for the caregiver themselves or between the caregiver and the cancer survivor. Caregiver experiences and needs may warrant explicit attention as survivors and caregivers are adjusting to a "new normal" that is no longer centered on getting through treatment.

Implications for cancer survivors

Patients and informal caregivers are often conceptualized as a "unit of care"; consideration of the needs of both is important for the provision of appropriate and effective health services.



http://ift.tt/2lMmpFm

Randomized trial of a clinic-based weight loss intervention in cancer survivors

Abstract

Background

This trial examined the efficacy of a clinic-based weight loss intervention in cancer survivors.

Methods

This single-center phase II trial randomized survivors of solid tumors and hematologic malignancies to a 15-week group-based weight loss intervention that included caloric restriction and physical activity (n = 30) or a wait-list control intervention (n = 30). The primary study outcome was body mass. Secondary study outcomes included body composition using dual-energy X-ray absorptiometry, physical fitness using the 6-min walk test (6MWT), and concentrations of serum biomarkers.

Results

Participants in the intervention group lost 5.6 ± 4.4% of baseline weight (4.6 ± 3.9 kg), whereas participants in the control group gained 0.2 ± 2.4% of baseline weight (0.2 ± 2.0 kg); intervention effect − 5.8% (95% CI − 7.8, − 3.8); − 4.8 kg (95% CI − 6.6, − 3.0); P = 0.0001. A larger proportion of participants in the intervention group lost ≥ 5% of baseline weight compared to the control group (43 vs 0%; P < 0.0001). The intervention led to reductions in fat mass (− 3.2 ± 0.7 kg; P < 0.0001), improvements in physical fitness (an increase of 22.6 ± 10.8 m on 6MWT; P = 0.03), and reductions in concentrations of insulin (− 7.7 ± 3.5 μU/mL; P = 0.004) and leptin (− 7.3 ± 4.0 ng/mL; P = 0.04).

Conclusion

A 15-week clinic-based weight loss intervention resulted in significant weight loss and improvements in body composition, physical fitness, and concentrations of serum biomarkers in cancer survivors.

Implications for cancer survivors

Weight loss programs provide a number of benefits for cancer survivors; survivors should inquire about the availability of lifestyle programs offered at their cancer center and within their local communities.



http://ift.tt/2lMmgli

8 more reasons why you should never run to treat patients

By EMS1 Staff If you're not running, then you're not concerned, right" Wrong. In an article about why EMS providers should never run to treat patients, an EMT outlined eight reasons on why not running to patients is not due to a lack of concern. On Facebook, the article received 1,000 Likes and was shared over 1,700 times. What do you think" Should there be any special circumstances for running ...

http://ift.tt/2hBMphQ

Application of Aorta-gonad-mesonephros Explant Culture System in Developmental Hematopoiesis

56557fig1.jpg

This protocol describes using cultured Aorta-Gonad-Mesonephros for expression analyses, colony-forming units in the culture and spleen, and long-term reconstitution to determine the effect of regulatory factors and signaling pathways on hematopoietic stem cell development. This has been demonstrated as an effective system for studying hematopoietic stem cell biology and function.

http://ift.tt/2zic0X5

Combined detection of Twist1, Snail1 and squamous cell carcinoma antigen for the prognostic evaluation of invasion and metastasis in cervical squamous cell carcinoma

Abstract

Background

Cervical cancer is one of the most common malignant tumours of the female reproductive system, ranking second only to breast cancer in morbidity worldwide. Essential features of the progression of cervical cancer are invasion and metastasis, which are closely related to disease prognosis and mortality rate. At the present time there is no effective method to evaluate cancer invasion and metastasis before surgery. Here we report our study on molecular changes in biopsy tissue for the prognostic evaluation of cancer invasion and metastasis.

Patients and methods

Expression of the epithelial–mesenchymal transition-inducing transcription factors Twist1 and Snail1 was detected by immunohistochemistry in 32 normal, 36 low-grade squamous intraepithelial neoplasia (LSIL), 54 high-grade squamous intraepithelial neoplasia (HSIL) and 320 cervical squamous cell carcinoma (CSCC) samples. The correlation between the expression of Twist1, Snail1 and squamous cell carcinoma antigen (SCCA) in CSCC tissues and clinical pathology results was evaluated. A transwell migration and invasion assay was used to explore the roles of Twist1 and Snail1 in the invasion of cancer cells. Lymph node metastasis and lymphovascular space invasion (LVSI) rates for the following groups were analysed: SCCA(+) group, Twist1(+) group, Snail1(+) group, Twist1(+)Snail1(+)group, Twist1(+)SCCA(+)group, Snail1(+)SCCA(+)group and Twist1(+)Snail1(+)SCCA(+) group.

Results

The expression of Twist1 and Snail1 was significantly upregulated in HSIL and CSCC (p < 0.05). Twist1 and Snail1 expression levels were associated with LVSI, lymph node metastasis and histological grade (p < 0.05) but not with age or FIGO stage (p > 0.05). The expression of SCCA was associated with LVSI, lymph node metastasis, FIGO stage and histological grade (p < 0.05) but not with age (p > 0.05). Twist1 was an independent factor contributing to the invasion ability of cervical cancer cells. In addition, the positive rate of lymph node metastasis and LVSI was higher in the Twist1(+)Snail1(+)SCCA(+) group than in the SCCA(+) group, Twist1(+) group and Snail1(+) group, respectively (p < 0.05).

Conclusion

Combined detection of Twist1 and Snail1 in SCCA-positive biopsy specimens may be a potential method for evaluating the invasion and metastasis of CSCC prior to surgery.



http://ift.tt/2AiS1FR

Vascular consideration in repair of total scalp avulsion

Jun Karibe<br />Oct 24, 2017; 2017:bcr-2017-220605-bcr-2017-220605<br />Unusual presentation of more common disease/injury

http://ift.tt/2xWkU8R

Use of a dynamic gait trainer for a child with thoracic level spinal cord injury

Wendy Altizer<br />Oct 10, 2017; 2017:bcr-2017-220756-bcr-2017-220756<br />Novel treatment (new drug/intervention; established drug/procedure in new situation)

http://ift.tt/2zaJ8xz

Severe liver injury due to Epsom salt naturopathy

Cyriac Abby Philips<br />Oct 2, 2017; 2017:bcr-2017-221718-bcr-2017-221718<br />Images in...

http://ift.tt/2xYuDf6

Could kinesiology taping help mitigate pain, breathlessness and abdominal-related symptoms in cancer?

Gourav Banerjee<br />Feb 24, 2017; 2017:bcr2016216695-bcr2016216695<br />case-report

http://ift.tt/2zcARcC

Genome-wide DNA methylation analysis reveals a prognostic classifier for non-metastatic colorectal cancer (ProMCol classifier)

Objective

Pathological staging used for the prediction of patient survival in colorectal cancer (CRC) provides only limited information.

Design

Here, a genome-wide study of DNA methylation was conducted for two cohorts of patients with non-metastatic CRC (screening cohort (n=572) and validation cohort (n=274)). A variable screening for prognostic CpG sites was performed in the screening cohort using marginal testing based on a Cox model and subsequent adjustment of the p-values via independent hypothesis weighting using the methylation difference between 34 pairs of tumour and normal mucosa tissue as auxiliary covariate. From the 1000 CpG sites with the smallest adjusted p-value, 20 CpG sites with the smallest Brier score for overall survival (OS) were selected. Applying principal component analysis, we derived a prognostic methylation-based classifier for patients with non-metastatic CRC (ProMCol classifier).

Results

This classifier was associated with OS in the screening (HR 0.51, 95% CI 0.41 to 0.63, p=6.2E–10) and the validation cohort (HR 0.61, 95% CI 0.45 to 0.82, p=0.001). The independent validation of the ProMCol classifier revealed a reduction of the prediction error for 3-year OS from 0.127, calculated only with standard clinical variables, to 0.120 combining the clinical variables with the classifier and for 4-year OS from 0.153 to 0.140. All results were confirmed for disease-specific survival.

Conclusion

The ProMCol classifier could improve the prognostic accuracy for patients with non-metastatic CRC.



http://ift.tt/2zc1OzB

Assessment of liver fibrosis with the gamma-glutamyl transpeptidase to platelet ratio: a multicentre validation in patients with HBV infection

We read with interest the study by Lemoine et al1 in which the gamma-glutamyl transpeptidase (GGT) to platelet ratio (GPR) was developed to stage fibrosis in patients with chronic hepatitis B (CHB). This study concluded that GPR is more accurate than the aspartate aminotransferase to platelet ratio index (APRI) and Fib-4 to stage liver fibrosis in patients with CHB. As China is a highly endemic area of CHB with estimated >74 million hepatitis B surface antigen (HBsAg)-positive patients,2 3 we conducted this multicentre study to validate the diagnostic performance of GPR in Chinese patients with CHB.

Treatment-naïve patients with positive HBsAg who underwent liver biopsy, Fibroscan (FS402, Echosens, France) and blood tests were included from three centres (Huai'an Fourth People's Hospital, Huai'an, China (January 2012–April 2016), Beijing You-An Hospital, Capital Medical University, Beijing, China (January 2014–June 2016) and Hepatology Hospital of Jilin Province, Jilin, China (January 2014–October 2016)). The patient...



http://ift.tt/2h8ICfb

Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit

Objective

Butyrate exerts metabolic benefits in mice and humans, the underlying mechanisms being still unclear. We aimed to investigate the effect of butyrate on appetite and energy expenditure, and to what extent these two components contribute to the beneficial metabolic effects of butyrate.

Design

Acute effects of butyrate on appetite and its method of action were investigated in mice following an intragastric gavage or intravenous injection of butyrate. To study the contribution of satiety to the metabolic benefits of butyrate, mice were fed a high-fat diet with butyrate, and an additional pair-fed group was included. Mechanistic involvement of the gut-brain neural circuit was investigated in vagotomised mice.

Results

Acute oral, but not intravenous, butyrate administration decreased food intake, suppressed the activity of orexigenic neurons that express neuropeptide Y in the hypothalamus, and decreased neuronal activity within the nucleus tractus solitarius and dorsal vagal complex in the brainstem. Chronic butyrate supplementation prevented diet-induced obesity, hyperinsulinaemia, hypertriglyceridaemia and hepatic steatosis, largely attributed to a reduction in food intake. Butyrate also modestly promoted fat oxidation and activated brown adipose tissue (BAT), evident from increased utilisation of plasma triglyceride-derived fatty acids. This effect was not due to the reduced food intake, but explained by an increased sympathetic outflow to BAT. Subdiaphragmatic vagotomy abolished the effects of butyrate on food intake as well as the stimulation of metabolic activity in BAT.

Conclusion

Butyrate acts on the gut-brain neural circuit to improve energy metabolism via reducing energy intake and enhancing fat oxidation by activating BAT.



http://ift.tt/2zbUowc

Deciphering the biology of IgG4-related disease: specific antigens and disease?

Immunoglobulin G4-related disease (IgG4-RD) is the name applied to a corticosteroid and/or B-cell depletion responsive illness, in which patients present with the consequences of usually multiorgan, relapsing and remitting, fibroinflammation.1 The disease is histologically characterised by obliterative phlebitis, storiform fibrosis and a dense lymphoplasmacytic infiltrate.2 IgG4-RD is not a new disease, but is benefiting from the application of new technologies in the pursuit of better biological understanding. The histologic enrichment of IgG4-expressing plasma cells is a diagnostic hallmark of disease that additionally serves as a biological phenomenon driving scientific evaluation.3 Key disease themes have evolved to include a large clonal expansion of activated plasmablasts and CD4+ cytotoxic, inflammatory and profibrotic lymphocytes. Therapeutically, a reduced frequency of CD4+ cytotoxic lymphocytes are seen after B-cell depletion; such therapy may consequently impact on antigen presentation.4–6 To date, the activity of IgG4-RD is not readily tracked by...



http://ift.tt/2h8Is7z

Long-term performance of colorectal cancer screening programmes based on the faecal immunochemical test

Background

The long-term performance of colorectal cancer (CRC) screening programmes based on a 2-year faecal immunochemical test (FIT) is still unclear.

Methods

In a sample of 50 to 69-year-olds repeatedly screened with the FIT (OC-Hemodia latex agglutination test; cut-off: 20 µg haemoglobin/g faeces), we examined: (1) the FIT positivity rate, the CRC and advanced adenoma detection rate and the FIT's positive predictive value (PPV) for advanced neoplasia, at each round of screening and (2) the cumulative CRC and advanced adenoma detection rate after five rounds of FIT.

Results

Over 12 years (2002–2014), 123 347 individuals were administered the FIT up to six times, and 781 CRCs and 4713 advanced adenomas were diagnosed. The CRC and advanced adenoma detection rates declined substantially from the first to the third (rate ratio (RR) 0.25, 95% CI 0.20 to 0.32) and second (RR 0.51, 95% CI 0.47 to 0.56) rounds, respectively, and then remained stable. The PPV for advanced neoplasia dropped by 18% in the second round (RR 0.82, 95% CI 0.77 to 0.89), with no further reduction thereafter due to a concomitant decline in the FIT positivity rate (RR first to sixth rounds: 0.56, 95% CI 0.53 to 0.60).

The cumulative CRC and advanced adenoma detection rates over five consecutive rounds were 8.5 (95% CI 7.8 to 9.2), and 58.9 (95% CI 56.9 to 61.0), respectively.

Conclusions

Repeated FIT significantly reduces the burden of colorectal disease while facilitating an efficient use of colonoscopy resources. The cumulative detection rate after five rounds of FIT is similar to primary screening with colonoscopy, supporting the need to account for the cumulative sensitivity of repeated FITs when evaluating the test's efficacy.



http://ift.tt/2zbUaoQ

Unexpected Cardiac Computed Tomography Findings in Patients With Postoperative Myocardial Injury

BACKGROUND: Postoperative myocardial injury (PMI) is a strong predictor of mortality after noncardiac surgery. PMI is believed to be attributable to coronary artery disease (CAD), yet its etiology is largely unclear. We aimed to quantify the prevalence of significant CAD in patients with and without PMI using coronary computed tomography angiography (CCTA). METHODS: This prospective cohort study included patients of 60 years or older without a history of cardiac disease and with and without PMI after intermediate- to high-risk noncardiac surgery. PMI was defined as any serum troponin I level ≥60 ng/L on the first 3 postoperative days. Main exclusion criteria were known cardiac disease and postoperative ischemic symptoms or electrocardiography abnormalities. Noninvasive imaging consisted of a postoperative CCTA. Main outcome was CAD defined as >50% coronary stenosis on CCTA. RESULTS: The analysis included 66 patients. Median peak troponin levels in the PMI (n = 46) and control group (n = 20) were 150 (interquartile range, 120–298) vs 15 (interquartile range, 10–31) ng/L (P

http://ift.tt/2xXo1xs

Teacher and Trustee: Examining the Ethics of Experiential Learning in Transesophageal Echocardiography Education

No abstract available

http://ift.tt/2zcZOF1

Artificial Ventilation: A Basic Clinical Guide

No abstract available

http://ift.tt/2xW2ghq

Neuroprotective Effects of Fasudil, a Rho-Kinase Inhibitor, After Spinal Cord Ischemia and Reperfusion in Rats

BACKGROUND: Excessive Rho/Rho-kinase pathway activation occurs subsequent to stroke. We examined the neuroprotective effects of pre- and posttreatment with fasudil (a Rho-kinase inhibitor) in a rat transient spinal cord ischemia-reperfusion model under normothermic conditions. METHODS: After approval by our animal research committee, male Sprague-Dawley rats were assigned to 1 of 6 groups: pre- and postcontrol (C); pre- and postfasudil (F); and pre- and postsham (S). Fasudil (10 mg/kg) or normal saline was administered intravenously over 30 minutes before ischemia in the pre-F or pre-C groups, and over 30 minutes after reperfusion in the post-F or post-C groups. Sham groups were not subjected to ischemia. Ischemia was induced by aortic occlusion using a balloon catheter combined with hypotension for 10 minutes. Neurologic deficit scores (NDS; 0–8 points) were assessed 1, 7, and 14 days after ischemia, and then histopathologic outcomes were assessed. RESULTS: NDS 7 and 14 days after ischemia in the pre-F group (median [range]; 3.5 [2–6] and 2.5 [0–6]) were lower than those in the pre-C group (5.5 [4–7] and 4.5 [4–6]; P = .046 and P = .049), whereas NDS in the post-F group and in the post-C group were not different. The numbers of intact neurons in the gray matter in the pre- and post-F groups (mean ± standard deviation [95% confidence interval]: 25 ± 7 [20–30] and 16 ± 5 [12–19]) were greater than those in the pre- and post-C groups (11 ± 5 [7–14] and 9 ± 3 [7–11]; P

http://ift.tt/2zbPDQI

The Society for Obstetric Anesthesia and Perinatology Consensus Statement on the Anesthetic Management of Pregnant and Postpartum Women Receiving Thromboprophylaxis or Higher Dose Anticoagulants

Venous thromboembolism is recognized as a leading cause of maternal death in the United States. Thromboprophylaxis has been highlighted as a key preventive measure to reduce venous thromboembolism–related maternal deaths. However, the expanded use of thromboprophylaxis in obstetrics will have a major impact on the use and timing of neuraxial analgesia and anesthesia for women undergoing vaginal or cesarean delivery and other obstetric surgeries. Experts from the Society of Obstetric Anesthesia and Perinatology, the American Society of Regional Anesthesia, and hematology have collaborated to develop this comprehensive, pregnancy-specific consensus statement on neuraxial procedures in obstetric patients receiving thromboprophylaxis or higher dose anticoagulants. To date, none of the existing anesthesia societies' recommendations have weighed the potential risks of neuraxial procedures in the presence of thromboprophylaxis, with the competing risks of general anesthesia with a potentially difficult airway, or maternal or fetal harm from avoidance or delayed neuraxial anesthesia. Furthermore, existing guidelines have not integrated the pharmacokinetics and pharmacodynamics of anticoagulants in the obstetric population. The goal of this consensus statement is to provide a practical guide of how to appropriately identify, prepare, and manage pregnant women receiving thromboprophylaxis or higher dose anticoagulants during the ante-, intra-, and postpartum periods. The tactics to facilitate multidisciplinary communication, evidence-based pharmacokinetic and spinal epidural hematoma data, and Decision Aids should help inform risk–benefit discussions with patients and facilitate shared decision making. Accepted for publication August 24, 2017. Funding: None. The authors declare no conflicts of interest. 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/KegmMq). The Appendix provides the full list of the SOAP VTE Taskforce members, along with their respective affiliations. Reprints will not be available from the authors. Address correspondence to Lisa Leffert, MD, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114. Address e-mail to lleffert@partners.org. © 2017 International Anesthesia Research Society

http://ift.tt/2xY9EsX

Tricuspid Regurgitation Due to Absent Tricuspid Valve Leaflet: Utility of Three-Dimensional Echocardiography

No abstract available

http://ift.tt/2zaGGXT

Can Lung Ultrasound Be the First-Line Tool for Evaluation of Intraoperative Hypoxemia?

No abstract available

http://ift.tt/2xW1PDO

Is It Time to Reconsider the Concepts of “Universal Donor” and “ABO Compatible” Transfusions?

No abstract available

http://ift.tt/2zbn8CR

The Anesthesia Records of Harvey Cushing and Ernest Codman

Hundreds of thousands of anesthesia records are created each day. The earliest records were prepared by 2 medical students in late 19th-century Boston. Ernest Codman and Harvey Cushing went on to become prominent surgeons and contributed much to the safety of the surgical patient. Cushing's career is celebrated due to his associations with William Stewart Halsted, Peter Bent Brigham Hospital, Yale University, in New Haven, Connecticut, and his biography of Sir William Osler. Codman is remembered for introducing the morbidity and mortality conference as well as his drive to improve outcomes and patient safety. We analyze every anesthetic record created by Codman and Cushing and provide both a historical context and perspective on many ways in which their doggedness, brilliance, and insight anticipated many advances that enhanced safety for patients undergoing surgical procedures. Accepted for publication September 4, 2017. Funding: This study received intramural support. The authors declare no conflicts of interest. 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/KegmMq). Reprints will not be available from the authors. Address correspondence to Sukumar P. Desai, MD, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115. Address e-mail to sdesai@partners.org. © 2017 International Anesthesia Research Society

http://ift.tt/2zczydP

Type B Aortic Dissection Diagnosed by Left-Sided Transthoracic Ultrasonography in a Woman With Preeclampsia

No abstract available

http://ift.tt/2xVYPYb

Percutaneous Closure of Complex Membranous Ventricular Septal Defect Under Transesophageal Echocardiographic Guidance

No abstract available

http://ift.tt/2zc1AWO

Colloids and the Microcirculation

Colloid solutions have been advocated for use in treating hypovolemia due to their expected effect on improving intravascular retention compared with crystalloid solutions. Because the ultimate desired effect of fluid resuscitation is the improvement of microcirculatory perfusion and tissue oxygenation, it is of interest to study the effects of colloids and crystalloids at the level of microcirculation under conditions of shock and fluid resuscitation, and to explore the potential benefits of using colloids in terms of recruiting the microcirculation under conditions of hypovolemia. This article reviews the physiochemical properties of the various types of colloid solutions (eg, gelatin, dextrans, hydroxyethyl starches, and albumin) and the effects that they have under various conditions of hypovolemia in experimental and clinical scenarios. Accepted for publication September 27, 2017. Funding: H.H. received funding from the China Scholarship Council (No. 201608110082) and the Organization Department of Beijing Municipal Committee (No. 2015000020124G072). C.I. has received honoraria and independent research grants from Fresenius-Kabi, Bad Homburg, Germany, and Baxter HealthCare, Deerfield, IL. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Can Ince, PhD, Department of Intensive Care, Erasmus Medical Center, s-Gravendijkwal 230, 3015 CE Rotterdam, the Netherlands. Address e-mail to c.ince@erasmusmc.nl. © 2017 International Anesthesia Research Society

http://ift.tt/2xXXujO

Transplantation of Schwann Cells Inside PVDF-TrFE Conduits to Bridge Transected Rat Spinal Cord Stumps to Promote Axon Regeneration Across the Gap

This article describes a technique to insert a hollow conduit between the spinal cord stumps after complete transection and fill with Schwann cells (SCs) and injectable basement membrane matrix in order to bridge and promote axon regeneration across the gap.

http://ift.tt/2zdDP0J

Chyluria: a scourge of our region

Rajan Kumar Sinha<br />Jul 6, 2015; 2015:bcr2014209188-bcr2014209188<br />case-report

http://ift.tt/2j0ZuF1

Vanishing lung syndrome mistaken for bilateral spontaneous pneumothorax

Faisal A Khasawneh<br />Oct 17, 2013; 2013:bcr2013201016-bcr2013201016<br />case-report

http://ift.tt/2Ai3Hs4

Devastating complication of silver nitrate instillation for the treatment of chyluria

Manish Garg<br />Sep 26, 2013; 2013:bcr2013201270-bcr2013201270<br />case-report

http://ift.tt/2j0ZjJR

Tuberculous gumma: a forgotten entity in the UK

Louise Parker<br />Sep 26, 2013; 2013:bcr2013010462-bcr2013010462<br />case-report

http://ift.tt/2AfGKG2

Asymptomatic submitral aneurysm: an uncommon complication of a common disease

G Vivek<br />Jun 24, 2013; 2013:bcr2013200032-bcr2013200032<br />case-report

http://ift.tt/2j0Z8OH

Successful treatment of massive intractable pericardial effusion in a patient with systemic lupus erythematosus with tocilizumab

Yasuyuki Kamata<br />Dec 21, 2012; 2012:bcr2012007834-bcr2012007834<br />case-report

http://ift.tt/2AfGF5c

Biomarkers related to bullous pemphigoid activity and outcome

Abstract

Bullous pemphigoid (BP) is the most common autoimmune sub-epidermal blistering disease of the skin. Investigation of the BP-associated pathophysiological processes during the last decades showed that the generation of auto-antibodies directed against the hemidesmosome proteins BP180 and BP230, a hallmark of the BP-associated autoimmune response, leads to the recruitment of inflammatory immune cells at the dermal-epidermal junction, and subsequently to the release of a large amount of inflammatory molecules involved in blister formation. Analysis in transversal and longitudinal studies of autoantibodies and inflammatory molecules production both at time of diagnosis and under treatment was mainly performed within the serum but also in the blister fluid. Some autoimmune or inflammatory molecules expression was related to the presence of clinical signs, while others were mere bystanders. In this review, we focused on the autoimmune and inflammatory molecules that have been identified as potential biomarkers of BP development and outcome.

This article is protected by copyright. All rights reserved.



http://ift.tt/2yrIWx5

Clogged arteries may be down to bacteria, not diet

An analysis of the chemical signatures of fatty deposits in clogged arteries found that they matched lipids produced by mouth and gut bacteria.

http://ift.tt/2zu2FfL

Long-term sequelae in survivors of childhood leukemia with Down syndrome: A childhood cancer survivor study report

BACKGROUND

Children with Down syndrome (DS) are at increased risk of developing acute leukemia and are more prone to acute toxicities. We studied the incidence and severity of chronic health conditions among survivors of childhood leukemia with DS compared with those without DS.

METHODS

Chronic health conditions reported by questionnaire were compared between 154 pediatric leukemia survivors with DS and 581 without DS, matched by leukemia, age at diagnosis, race/ethnicity, sex, radiation location and chemotherapy exposure using Cox models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Subjects were selected from 7139 5-year survivors of leukemia in the Childhood Cancer Survivor Study.

RESULTS

Risk of at least 1 late onset chronic health condition (grade 1-5) was similar in the DS population compared with the non-DS group (HR, 1.1; 95% CI, 0.7-1.5). Serious chronic health conditions (grade 3-5) were more common in DS survivors (HR, 1.7; 95% CI, 1.1-2.6), as were ≥ 3 chronic health conditions (grades 1-5) (HR, 1.7; 95% CI, 1.2-2.4). The 25-year cumulative incidence of any condition (grades 1-5) was 83% for DS survivors and 69% for non-DS survivors.

CONCLUSION

Leukemia survivors with DS have therapy-related chronic health conditions comparable to those of similarly treated survivors without DS, with a few notable exceptions: 1) an increased risk of cataracts, hearing loss, and thyroid dysfunction compared with survivors without DS (though these are known risks in the DS population), 2) decreased risk of second cancers, and 3) increased risk of severe or multiple conditions. Practitioners should be aware of these risks during and after therapy. Cancer 2017. © 2017 American Cancer Society.



http://ift.tt/2hBZ1FM

Predictors of Intubation in Patients With Acute Hypoxemic Respiratory Failure Treated With a Noninvasive Oxygenation Strategy

Objectives: In patients with acute hypoxemic respiratory failure, noninvasive ventilation and high-flow nasal cannula oxygen are alternative strategies to conventional oxygen therapy. Endotracheal intubation is frequently needed in these patients with a risk of delay, and early predictors of failure may help clinicians to decide early. We aimed to identify factors associated with intubation in patients with acute hypoxemic respiratory failure treated with different noninvasive oxygenation techniques. Design: Post hoc analysis of a randomized clinical trial. Setting: Twenty-three ICUs. Patients: Patients with a respiratory rate greater than 25 breaths/min and a PaO2/FIO2 ratio less than or equal to 300 mm Hg. Intervention: Patients were treated with standard oxygen, high-flow nasal cannula oxygen, or noninvasive ventilation. Measurement and Main Results: Respiratory variables one hour after treatment initiation. Under standard oxygen, patients with a respiratory rate greater than or equal to 30 breaths/min were more likely to need intubation (odds ratio, 2.76; 95% CI, 1.13–6.75; p = 0.03). One hour after high-flow nasal cannula oxygen initiation, increased heart rate was the only factor associated with intubation. One hour after noninvasive ventilation initiation, a PaO2/FIO2 ratio less than or equal to 200 mm Hg and a tidal volume greater than 9 mL/kg of predicted body weight were independent predictors of intubation (adjusted odds ratio, 4.26; 95% CI, 1.62–11.16; p = 0.003 and adjusted odds ratio, 3.14; 95% CI, 1.22–8.06; p = 0.02, respectively). A tidal volume above 9 mL/kg during noninvasive ventilation remained independently associated with 90-day mortality. Conclusions: In patients with acute hypoxemic respiratory failure breathing spontaneously, the respiratory rate was a predictor of intubation under standard oxygen, but not under high-flow nasal cannula oxygen or noninvasive ventilation. A PaO2/FIO2 below 200 mm Hg and a high tidal volume greater than 9 mL/kg were the two strong predictors of intubation under noninvasive ventilation. 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). This study was coordinated at Réanimation Médicale, CHU de Poitiers, Poitiers, France and performed in 23 centers in France and Belgium. Dr. Frat reports grants, personal fees, and nonfinancial support from the "Fisher & Paykel HealthCare" firm, during the conduct of the study; personal fees and nonfinancial support from SOS oxygène, outside the submitted work. Dr. Coudroy reports nonfinancial support from MSD, outside the submitted work. Dr. Girault reports nonfinancial support and other from Fisher & Paykel Healthcare, during the conduct of the study; personal fees from Fisher & Paykel Healthcare, outside the submitted work. Dr. Demoule reports personal fees from Covidien, grants and personal fees from Maquet, grants from Philips, personal fees from MSD, nonfinancial support from Dräger, outside the submitted work. Dr. Ricard reports coverage by Fisher & Paykel Healthcare of expenses to attend scientific meetings. Dr. Mercat reports personal fees from Faron Pharmaceuticals, personal fees from Air Liquide Medical Systems, grants and personal fees from Fisher-Paykel, grants and personal fees from Covidien, outside the submitted work. In addition, Dr. Mercat has a patent General Electric licensed. Dr. Brochard reports grants and nonfinancial support from Fisher & Paykel, grants and nonfinancial support from Covidien, nonfinancial support from Philips, nonfinancial support from Maquet, nonfinancial support from General Electric, grants from Air Liquide, outside the submitted work. Dr. Robert reports nonfinancial support from Fresenius Medical Care, from Baxter Gambro, outside the submitted work. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: jean-pierre.frat@chu-poitiers.fr Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://ift.tt/2zaMQHx

Acute Systemic Complications of Convulsive Status Epilepticus—A Systematic Review

Objectives: Status epilepticus is a neurologic emergency with high morbidity and mortality requiring neurointensive care and treatment of systemic complications. This systematic review compiles the current literature on acute systemic complications of generalized convulsive status epilepticus in adults and their immediate clinical impact along with recommendations for optimal neurointensive care. Data Sources: We searched PubMed, Medline, Embase, and the Cochrane library for articles published between 1960 and 2016 and reporting on systemic complications of convulsive status epilepticus. Study Selection: All identified studies were screened for eligibility by two independent reviewers. Data Extraction: Key data were extracted using standardized data collection forms. Data Synthesis: Thirty-two of 3,046 screened articles were included. Acute manifestations and complications reported in association with generalized convulsive status epilepticus can affect all organ systems fueling complex cascades and multiple organ interactions. Most reported complications result from generalized excessive muscle contractions that increase body temperature and serum potassium levels and may interfere with proper and coordinated function of respiratory muscles followed by hypoxia and respiratory acidosis. Increased plasma catecholamines can cause a decay of skeletal muscle cells and cardiac function, including stress cardiomyopathy. Systemic complications are often underestimated or misinterpreted as they may mimic underlying causes of generalized convulsive status epilepticus or treatment-related adverse events. Conclusions: Management of generalized convulsive status epilepticus should center on the administration of antiseizure drugs, treatment of the underlying causes, and the attendant systemic consequences to prevent secondary seizure-related injuries. Heightened awareness, systematic clinical assessment, and diagnostic workup and management based on the proposed algorithm are advocated as they are keys to optimal outcome. 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). This work was performed at Universtiy Hospital Basel, Basel, Switzerland. Dr. Sutter received research grants from the Swiss National Foundation (No 320030_169379), the Research Fund of the University Basel, the Scientific Society Basel, and the Gottfried Julia Bangerter-Rhyner Foundation. He received personal grants from the Union Chimique Belge (UCB)-pharma and holds stocks from Novartis and Roche. Dr. Rüegg's institution received funding from UCB, Novartis, and Swiss National Science Foundation Grants: grant number 320030_169379/1 and coapplicant for grants numbers 33CM30_125115/1 and 33CM30_140338/1; he disclosed that he is the President of the Swiss League against Epilepsy (no payments), Editor of EPILEPTOLOGIE (Journal of the Swiss League against Epilepsy) (no payments), and Editor of the Swiss EEG Bulletin (payments from UCB); he received honoraria from serving on the scientific advisory boards of Desitin, Eisai, GlaxoSmithKline (GSK), and UCB-pharma, travel grants from GSK, Janssen-Cilag, UCB-pharma, speaker fees from UCB-pharma and from serving as a consultant for Eisai, GSK, Janssen-Cilag, Pfizer, Novartis, and UCB-pharma; and he does not hold any stocks of any pharmaceutical industries or manufacturers of medical devices. Dr. Kaplan received funding from the Amercian Clinical Neurophysiology Society (board) and from serving as an expert witness; he has provided unsponsored grand rounds; and he published books on electroencephalogram (EEG), status epilepticus and epilepsy, and is on Qatar Research Foundation grant on continuous EEG monitoring in status epilepticus. The remaining authors have disclosed that they do not have any potential conflicts of interest. Dr. Sutter, Dittrich, and Dr. Semmlack have designed this review, did the literature search, analyzed the data, written the article, and designed the tables and figures. Drs. Rüegg, Marsch, and Kaplan have analyzed the data, written parts of the article, and revised the article. For information regarding this article, E-mail: Raoul.Sutter@usb.ch Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://ift.tt/2za990f

EMS Artwork: Responders continue to heal, remain Vegas Strong

There were many first responders who were off duty when the Las Vegas shooting happened, but they came into work and offered to help. They knew their co-workers would be overwhelmed with patients. This event didn't only impact the crews that were on scene, but all first responders in Las Vegas. All sales from this image will go to the Las Vegas First Responder Mental Health Fund that has been set ...

http://ift.tt/2zcrYQp

EMS Artwork: Responders continue to heal, remain Vegas Strong

This AMR crew was working the night a gunman opened fire on 22,000 Las Vegas concert attendees

http://ift.tt/2gYYSM1

Inside EMS Podcast: Tips to pass the NREMT exam

Our co-hosts also discuss how to go from the truck to stepping into an instructor role

http://ift.tt/2hAB2qy

An investigation into the range dependence of target delineation strategies for stereotactic lung radiotherapy

Abstract

Background

The "gold standard" approach for defining an internal target volume (ITV) is using 10 gross tumor volume (GTV) phases delineated over the course of one respiratory cycle. However, different sites have adopted several alternative techniques which compress all temporal information into one CT image set to optimize work flow efficiency. The purpose of this study is to evaluate alternative target segmentation strategies with respect to the 10 phase gold standard.

Methods

A Quasar respiratory motion phantom was employed to simulate lung tumor movement. Utilizing 4DCT imaging, a gold standard ITV was created by merging 10 GTV time resolved image sets. Four alternative planed ITV's were compared using free breathing (FB), average intensity projection (AIP), maximum image projection (MIP), and an augmented FB (FB-Aug) set where the ITV included structures from FB plus max-inhale/exhale image sets. Statistical analysis was performed using the Dice similarity coefficient (DSC). Seventeen patients previously treated for lung SBRT were also included in this retroactive study.

Results

PTV's derived from the FB image set are the least comparable with the 10 phase benchmark (DSC = 0.740-0.408). For phantom target motion greater than 1 cm, FB and AIP ITV delineation exceeded the 10 phase benchmark by 2% or greater, whereas MIP target segmentation was found to be consistently within 2% agreement with the gold standard (DSC > 0.878). Clinically, however, the FB-Aug method proved to be most favorable for tumor movement up to 2 cm (DSC = 0.881 ± 0.056).

Conclusion

Our results indicate the range of tumor motion dictates the accuracy of the defined PTV with respect to the gold standard. When considering delineation efficiency relative to the 10 phase benchmark, the FB-Aug technique presents a potentially proficient and viable clinical alternative. Among various techniques used for image segmentation, a judicious balance between accuracy and efficiency is inherently required to account for tumor trajectory, range and rate of mobility.



http://ift.tt/2hAOJFY

Next generation sequencing: clinical applications in solid tumours

Summary

Next generation sequencing (NGS) has unravelled the genetic alterations that underlie the pathogenesis of cancer. It is now becoming integrated into routine clinical diagnostics of malignant tumours. NGS supports diagnosis, identifies therapeutic targets, reveals resistance mechanisms and facilitates disease monitoring. It takes a central function in the implementation of cancer therapies adapted to the molecular alterations of tumours.



http://ift.tt/2hACQQj

Biophysical Characterization of Genetically Encoded Voltage Sensor ASAP1: Dynamic Range Improvement

Recent work has introduced a new fluorescent voltage sensor, ASAP1, which can monitor rapid trains of action potentials in cultured neurons. This indicator is based on the Gallus gallus voltage-sensitive phosphatase with the phosphatase domain removed and a circularly permuted GFP placed in the S3-S4 linker. However, many of the biophysical details of this indicator remain unknown. In this work, we study the biophysical properties of ASAP1. Using the cut-open voltage clamp technique, we have simultaneously recorded fluorescence signals and gating currents from Xenopus laevis oocytes expressing ASAP1.

http://ift.tt/2iXnnxn

Mapping Hydrophobic Tunnels and Cavities in Neuroglobin with Noble Gas under Pressure

Internal cavities are crucial for conformational flexibility of proteins and can be mapped through noble gas diffusion and docking. Here we investigate the hydrophobic cavities and tunnel network in neuroglobin (Ngb), a hexacoordinated heme protein likely to be involved in neuroprotection, using crystallography under noble gas pressure, mostly at room temperature. In murine Ngb, a large internal cavity is involved in the heme sliding mechanism to achieve binding of gaseous ligands through coordination to the heme iron.

http://ift.tt/2Agvppp

Biophysical Characterization of Genetically Encoded Voltage Sensor ASAP1: Dynamic Range Improvement

Recent work has introduced a new fluorescent voltage sensor, ASAP1, which can monitor rapid trains of action potentials in cultured neurons. This indicator is based on the Gallus gallus voltage-sensitive phosphatase with the phosphatase domain removed and a circularly permuted GFP placed in the S3-S4 linker. However, many of the biophysical details of this indicator remain unknown. In this work, we study the biophysical properties of ASAP1. Using the cut-open voltage clamp technique, we have simultaneously recorded fluorescence signals and gating currents from Xenopus laevis oocytes expressing ASAP1.

http://ift.tt/2iXnnxn

Mapping Hydrophobic Tunnels and Cavities in Neuroglobin with Noble Gas under Pressure

Internal cavities are crucial for conformational flexibility of proteins and can be mapped through noble gas diffusion and docking. Here we investigate the hydrophobic cavities and tunnel network in neuroglobin (Ngb), a hexacoordinated heme protein likely to be involved in neuroprotection, using crystallography under noble gas pressure, mostly at room temperature. In murine Ngb, a large internal cavity is involved in the heme sliding mechanism to achieve binding of gaseous ligands through coordination to the heme iron.

http://ift.tt/2Agvppp