British Journal of Surgery, EarlyView.
https://ift.tt/2H9Cyi6
Τρίτη 17 Απριλίου 2018
Cost–utility analysis of bariatric surgery
c‐Src inhibitor selectively inhibits triple‐negative breast cancer overexpressed Vimentin in vitro and in vivo
Cancer Science, EarlyView.
https://ift.tt/2H851VF
Hispidulin suppresses cell growth and metastasis by targeting PIM1 through JAK2/STAT3 signaling in colorectal cancer
Cancer Science, EarlyView.
https://ift.tt/2qGPm4D
Ictal Interictal Continuum Patterns
Abstract
Purpose of review
To present data available on the epidemiology and significance of rhythmic and periodic patterns that lie on the ictal interictal continuum and propose an algorithm for the clinical approach to patients exhibiting these patterns.
Recent findings
There is accumulating evidence on the prognostic implications of various rhythmic and periodic patterns in the critically ill population. These patterns are not only associated with increased seizure risk but have also been associated with worse outcome and increased long-term risk of epilepsy in recent studies. There is emerging evidence suggesting that certain EEG features as well as ancillary studies including serum, neuroimaging, and invasive multimodality monitory can assist in the risk stratification of neuronal injury associated with these patterns, allowing for a targeted approach to these patterns.
Summary
We present a case illustrating the clinical nuances of these patterns. We propose an algorithm for a personalized and targeted approach to ictal interictal patterns based on risk stratification according to clinical, EEG, imaging, and invasive monitoring markers.
https://ift.tt/2qLl7un
Quo Vadis—Do Immunotherapies Have a Role in Glioblastoma?
Abstract
Purpose of review
More effective therapies for glioblastoma are urgently needed. Immunotherapeutic strategies appear particularly promising and are therefore intensively studied. This article reviews the current understanding of the immunosuppressive glioblastoma microenvironment, discusses the rationale behind various immunotherapies, and outlines the findings of several recently published clinical studies.
Recent findings
The results of CheckMate-143 indicated that nivolumab is not superior to bevacizumab in patients with recurrent glioblastoma. A first-in man exploratory study evaluating EGFRvIII-specific CAR T cells for patients with newly diagnosed glioblastoma demonstrated overall safety of CAR T cell therapy and effective target recognition. A pilot study evaluating treatment with adoptively transferred CMV-specific T cells combined with a CMV-specific DC vaccine was found to be safe and resulted in increased polyclonality of CMV-specific T cells in vivo.
Summary
Despite the success of immunotherapies in many cancers, clinical evidence supporting their efficacy for patients with glioblastoma is still lacking. Nevertheless, the recently published studies provide important proof-of-concept in several areas of immunotherapy research. The careful and critical interpretation of these results will enhance our understanding of the opportunities and challenges of immunotherapies for high-grade gliomas and improve the immunotherapeutic strategies investigated in future clinical trials.
https://ift.tt/2EVaj0M
Randomised clinical trial: gastrointestinal events in arthritis patients treated with celecoxib, ibuprofen or naproxen in the PRECISION trial
Alimentary Pharmacology &Therapeutics, EarlyView.
https://ift.tt/2ETn5g9
Adjuvant chemotherapy in patients with operable granulosa cell tumors of the ovary: a surveillance, epidemiology, and end results cohort study
Cancer Medicine, EarlyView.
https://ift.tt/2H9l55q
To stent or not to stent: the use of transanastomotic biliary stents in liver transplantation and patient outcomes
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2Hwn07r
Issue Information
Clinical Oral Implants Research, Volume 29, Issue 4, Page i-ii, April 2018.
https://ift.tt/2qETHoY
The role of ketogenic diets in the therapeutic management of adult and paediatric gliomas: a systematic review
CNS Oncology, Ahead of Print.
https://ift.tt/2HABS4K
Early-Detection Sequencing Assays Prove Highly Specific [News in Brief]
Ultrasensitive DNA-sequencing methods demonstrate feasibility of designing a blood test for cancer screening.
https://ift.tt/2H9aag8
Vision for NCI Outlined by New Director [News in Brief]
At the AACR Annual Meeting, Norman Sharpless, MD, described four broad areas where the agency can make advances and accelerate progress against cancer.
https://ift.tt/2qHnq0z
Combo Therapy for Lung Cancer Extends Survival [News in Brief]
Pembrolizumab plus chemo improves OS and PFS in patients with advanced NSCLC.
https://ift.tt/2H7Aur0
Whole Genome Sequence of an Edible and Potential Medicinal Fungus, Cordyceps guangdongensis
Cordyceps guangdongensis is an edible fungus which was approved as a novel food by the Chinese Ministry of Public Health in 2013. It also has a broad prospect of application in pharmaceutical industries, with many medicinal activities. In this study, the whole genome of C. guangdongensis GD15, a single spore isolate from a wild strain, was sequenced and assembled with Illumina and PacBio sequencing technology. The generated genome is 29.05 Mb in size, comprising nine scaffolds with an average GC content of 57.01%. It is predicted to contain a total of 9150 protein-coding genes. Sequence identification and comparative analysis indicated that the assembled scaffolds contained two complete chromosomes and four single-end chromosomes, showing a high level assembly. Gene annotation revealed a diversity of transposons that could contribute to the genome size and evolution. Besides, approximately 15.57% and 12.01% genes involved in metabolic processes were annotated by KEGG and COG respectively. Genes belonging to CAZymes accounted for 3.15% of the total genes. In addition, 435 transcription factors, involved in various biological processes, were identified. Among the identified transcription factors, the fungal transcription regulatory proteins (18.39%) and fungal-specific transcription factors (19.77%) represented the two largest classes of transcription factors. This genomic resource provided a new insight into better understanding the relevance of phenotypic characters and genetic mechanisms in C. guangdongensis.
https://ift.tt/2vnTv38
Effect of Larval Nutrition on Maternal mRNA Contribution to the Drosophila Egg
Embryonic development begins under the control of maternal gene products, mRNAs and proteins that the mother deposits into the egg; the zygotic genome is activated some time later. Maternal control of early development is conserved across metazoans. Gene products contributed by mothers are critical to many early developmental processes, and set up trajectories for the rest of development. Maternal deposition of these factors is an often-overlooked aspect of parental investment. If the mother experiences challenging environmental conditions, such as poor nutrition, previous studies in Drosophila melanogaster have demonstrated a plastic response wherein these mothers may produce larger eggs to buffer the offspring against the same difficult environment. This additional investment can produce offspring that are more fit in the challenging environment. With this study, we ask whether D. melanogaster mothers who experience poor nutrition during their own development change their gene product contribution to the egg. We perform mRNA-Seq on eggs at a stage where all mRNAs are maternally derived, from mothers with different degrees of nutritional limitation. We find that nutritional limitation produces similar transcript changes at all degrees of limitation tested. Genes that have lower transcript abundance in nutritionally limited mothers are those involved in translation, which is likely one of the most energetically costly processes occurring in the early embryo. We find an increase in transcripts for transport and localization of macromolecules, and for the electron transport chain. The eggs produced by nutrition-limited mothers show a plastic response in mRNA deposition, which may better prepare the future embryo for development in a nutrition-limited environment.
https://ift.tt/2JV4R1t
A Catalogue of Putative cis-Regulatory Interactions Between Long Non-coding RNAs and Proximal Coding Genes Based on Correlative Analysis Across Diverse Human Tumors
Antisense transcripts and other long non-coding RNAs are pervasive in mammalian cells, and some of these molecules have been proposed to regulate proximal protein-coding genes in cis. For example, non-coding transcription can contribute to inactivation of tumor suppressor genes in cancer, and antisense transcripts have been implicated in the epigenetic inactivation of imprinted genes. However, our knowledge is still limited and more such regulatory interactions likely await discovery. Here, we make use of available gene expression data from a large compendium of human tumors to generate hypotheses regarding non-coding-to-coding cis-regulatory relationships with emphasis on negative associations, as these are less likely to arise for reasons other than cis-regulation. We document a large number of possible regulatory interactions, including 193 coding/non-coding pairs that show expression patterns compatible with negative cis-regulation. Importantly, by this approach we capture several known cases, and many of the involved coding genes have known roles in cancer. Our study provides a large catalogue of putative non-coding/coding cis-regulatory pairs that may serve as a basis for further experimental validation and characterization.
https://ift.tt/2vkFOlr
Deptor is a novel target of Wnt/{beta}-catenin/c-Myc and contributes to colorectal cancer cell growth
Activation of the Wnt/β-catenin signaling pathway drives colorectal cancer (CRC) growth by deregulating expression of downstream target genes including the c-Myc proto-oncogene. The critical targets that mediate the functions of oncogenic c-Myc in CRC have yet to be fully elucidated. Previously, we showed that activation of PI3K/Akt/mTOR contributes to CRC growth and metastasis. Here we show that Deptor, a suppressor of mTOR, is a direct target of Wnt/β-catenin/c-Myc signaling in CRC cells. Inhibition of Wnt/β-catenin or knockdown of c-Myc decreased, while activation of Wnt/β-catenin or overexpression of c-Myc increased, the expression of Deptor. c-Myc bound the promoter of Deptor and transcriptionally regulated Deptor expression. Inhibition of Wnt/β-catenin/c-Myc signaling increased mTOR activation, and the combination of Wnt and Akt/mTOR inhibitors enhanced inhibition of CRC cell growth in vitro and in vivo. Deptor expression was increased in CRC cells; knockdown of Deptor induced differentiation, decreased expression of B lymphoma Mo-MLV insertion region 1 (Bmi1), and decreased proliferation in CRC cell lines and primary human CRC cells. Importantly, our work identifies Deptor as a downstream target of the Wnt/β-catenin/c-Myc signaling pathway, acting as a tumor promoter in CRC cells. Moreover, we provide a molecular basis for the synergistic combination of Wnt and mTOR inhibitors in treating CRC with elevated c-Myc.
https://ift.tt/2qHlyF5
Gallium-67/68-labeled antibody fragments for immuno-SPECT/PET show low renal radioactivity without loss of tumor uptake
Purpose:This study was undertaken to evaluate the renal radioactivity levels of a newly designed 67Ga-labeled antibody fragment with a linkage cleaved by enzymes present on the brush border membrane (BBM) lining the lumen of the renal tubule. Experimental Design: 67Ga-labeled S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-Bn-NOTA) was conjugated with an antibody Fab fragment through a Met-Val-Lys linkage (67Ga-NOTA-MVK-Fab) considering that a Met-Val sequence is a substrate of enzymes on the renal BBM and 67Ga-NOTA-Met is excreted from the kidney into the urine. The enzymatic recognition of the linkage was evaluated with a low-molecular-weight 67Ga-NOTA-Met-Val-Lys derivative. Biodistribution of radioactivity after injection of 67Ga-NOTA-MVK-Fab into mice was compared with 67Ga-NOTA-conjugated Fab fragments through a Met-Ile linkage that liberates 67Ga-NOTA-Met (67Ga-NOTA-MI-Fab) or a conventional thiourea linkage (67Ga-NOTA-Fab). Results: The MVK linkage remained stable in plasma and was recognized by enzymes on renal BBM to liberate 67Ga-NOTA-Met. When injected into mice, all three 67Ga-labeled Fab exhibited similar blood clearance rates and tumor accumulation. Significant differences were observed in the kidney where 67Ga-NOTA-MVK-Fab registered the lowest renal radioactivity levels from early postinjection time (p < 0.05), followed by 67Ga-NOTA-MI-Fab, which was well reflected in the SPECT/CT images. Conclusions: These findings indicated that our proposal of liberating a radiolabeled compound to urinary excretion from antibody fragments at the renal BBM to reduce the renal radioactivity levels was applicable to 67/68Ga-labeled antibody fragments. Since antibody fragments and constructs share similar metabolic fates in the kidney, the present labeling procedure would also apply to a variety of antibody fragments and constructs of interest.
https://ift.tt/2EVwsvS
Strategic therapeutic targeting to overcome venetoclax resistance in aggressive B-cell lymphomas
Purpose: B-cell lymphoma-2 (BCL-2), an anti-apoptotic protein often dysregulated in B-cell lymphomas, promotes cell survival and provides protection from stress. A recent Phase I first-in-human study of the BCL-2 inhibitor venetoclax in non-Hodgkin lymphoma showed an overall response rate of 44%. These promising clinical results prompted our examination of the biological effects and mechanism of action underlying venetoclax activity in aggressive B-cell lymphoma, including mantle cell lymphoma (MCL) and diffuse large B cell lymphoma (DLBCL). Experimental Design: MCL and DLBCL cell lines, primary patient samples, and in vivo patient-derived xenograft (PDX) models were utilized to examine venetoclax efficacy. Furthermore, the mechanisms underlying venetoclax response and the development of venetoclax resistance were evaluated using proteomics analysis and Western blotting. Results: Potential biomarkers linked to venetoclax activity and targeted combination therapies that can augment venetoclax response were identified. We demonstrate that DLBCL and MCL cell lines, primary patient samples, and PDX mouse models expressing high BCL-2 levels are extremely sensitive to venetoclax treatment. Proteomics studies showed that venetoclax substantially alters the expression levels and phosphorylation status of key proteins involved in cellular processes, including the DNA damage response, cell metabolism, cell growth/survival, and apoptosis. Short- and long-term exposure to venetoclax inhibited PTEN expression, leading to enhanced AKT pathway activation and concomitant susceptibility to PI3K/AKT inhibition. Intrinsic venetoclax-resistant cells possess high AKT activation and are highly sensitive to PI3K/AKT inhibition. Conclusions: These findings demonstrate the on-target effect of venetoclax and offer potential mechanisms to overcome acquired and intrinsic venetoclax resistance through PI3K/AKT inhibition.
https://ift.tt/2Hz0ds1
Fratricide of NK Cells in Daratumumab Therapy for Multiple Myeloma Overcome by Ex Vivo Expanded Autologous NK Cells
Purpose: Daratumumab and its use in combination with other agents is becoming a new standard of care for treatment of multiple myeloma (MM). We mechanistically studied how daratumumab acts on NK cells. Experimental Design: Quantities of NK cells in peripheral blood (PB) and/or bone marrow (BM) of MM patients or healthy donors were examined by flow cytometry. NK cell apoptosis and the associated mechanism were assessed by flow cytometry and immunoblotting. Patients' NK cells were expanded in vitro using feeder cells. Combination treatment of daratumumab and expanded NK cells was performed using an MM.1S xenograft animal model. Results: CD38–/low NK cells survived, while CD38+ NK cells were almost completely eliminated, in PB and BM of daratumumab-treated MM patients. NK cell depletion occurred due to daratumumab-induced NK cell fratricide via antibody-dependent cellular cytotoxicity (ADCC). Consequently, CD38–/low NK cells were more effective for eradicating MM cells than were CD38+ NK cells in the presence of daratumumab. Blockade of CD38 with the F(ab)2 fragments of daratumumab inhibited the antibody-mediated NK cell fratricide. CD38–/low NK cells displayed a significantly better potential for expansion than CD38+ NK cells, and the expanded NK cells derived from the former population were more cytotoxic than those derived from the latter against MM cells. Therefore, infusion of ex vivo-expanded autologous NK cells from daratumumab-treated patients may improve the antibody therapy. Conclusions: We unravel a fratricide mechanism for daratumumab-mediated NK cell depletion and provide a potential therapeutic strategy to overcome this side effect in daratumumab-treated MM patients.
https://ift.tt/2Hz0nzD
Targeting Galectin-1 impairs castration-resistant prostate cancer progression and invasion
Purpose: The majority of prostate cancer (PCa) patients who are treated with androgen deprivation therapy (ADT) will eventually develop fatal metastatic castration-resistant prostate cancer (mCRPC). Currently, there are no effective durable therapies for patients with mCRPC. High expression of Galectin-1 (Gal-1) is associated with PCa progression and poor clinical outcome. The role of Gal-1 in tumor progression are largely unknown. Here we characterized Gal-1 functions and evaluated the therapeutic effects of a newly developed Gal-1inhibitor, LLS30, in mCRPC. Experimental Design: Cell viability, colony formation, migration and invasion assays were performed to examine the effects of inhibition of Gal-1 in CRPC cells. We used two human CRPC xenograft models to assess growth inhibitory effects of LLS30. Genome-wide gene expression analysis was conducted to elucidate the effects of LLS30 on metastatic PC3 cells. Results: Gal-1 was highly expressed in CRPC cells, but not in androgen-sensitive cells. Gal-1 knockdown significantly inhibited CRPC cells' growth, anchorage independent growth, migration and invasion through the suppression of AR and Akt signaling. LLS30 targets Gal-1 as an allosteric inhibitor, and decreases Gal-1 binding affinity to its binding partners. LLS30 showed in vivo efficacy in both AR positive and AR negative xenograft models. LLS30 not only can potentiate the anti-tumor effect of docetaxel to cause complete regression of tumors, but can also effectively inhibit the invasion and metastasis of PCa cells in vivo. Conclusions:Our study provides evidence that Gal-1 is an important target for mCRPC therapy, and LLS30 is a promising small molecule compound that can potentially overcome mCRPC.
https://ift.tt/2vnqvIL
Fish-Mouth Papilla
A 53-year-old man presented with postprandial epigastric pain and weight loss for 2 months. He had no significant medical or family history. Physical examination was normal and the laboratory results were unremarkable. We performed an upper endoscopy, which showed a normal stomach and duodenum. However, the major papilla (Figure A) had an unusual appearance. We examined the patient using a duodenoscope and observed a fish-mouth–like papilla extruding thick mucus (Supplementary Video 1). The fish-mouth appearance of papilla, although not always present (prevalence, 50%), is pathognomonic and specific (91%) for intraductal papillary mucinous neoplasm (IPMN) of the pancreas.
https://ift.tt/2HaoXTY
Rectoprostate Fistula After Endoscopic Treatment of Radiation Proctitis
An 80-year-old man was referred for severe, persistent rectal pain.
https://ift.tt/2HICUtn
Carbonic anhydrase 9 expression in well-differentiated pancreatic neuroendocrine neoplasms might be associated with aggressive behavior and poor survival
Abstract
Well-differentiated pancreatic neuroendocrine neoplasms/tumors (PanNETs) are rare neoplasms with diverse clinical behavior. Biomarker discovery is important for predicting clinical course and prognosis of PanNET patients. Carbonic anhydrase 9 (CA9) and vimentin are hypoxia and epithelial-mesenchymal transition-related proteins of which expression in many carcinomas has been associated with poor prognosis, but their significance in PanNET has yet to be determined. We assessed CA9 and vimentin expression in 164 PanNETs and compared this with clinicopathologic characteristics. CA9 expression was observed in normal islets, while neuroendocrine microadenomas and small (< 1 cm) PanNETs showed loss of CA9 expression. CA9 and vimentin expression was observed in 38 (23%) and 36 (22%) of PanNETs, respectively. CA9 expression was associated with larger size (p = 0.001), higher grade (p < 0.001), higher pT category (p < 0.001), lymph node (p = 0.003) and distant (p = 0.047) metastases, higher AJCC stage (p < 0.001), and lymphovascular (p < 0.001) and perineural (p = 0.002) invasion. PanNET patients with CA9 expression had a shorter recurrence-free survival (5-year survival rate 47%) than those without CA9 expression (76%) by univariate (p = 0.001) but not multivariate analysis. Vimentin expression correlated with CA9 expression (p < 0.001) but not with other clinicopathologic factors. In conclusion, CA9 expression was observed in normal islets, while neuroendocrine microadenomas and small (< 1 cm) PanNETs showed CA9 expression loss. CA9 expression gradually reappeared in larger PanNETs, and this was associated with clinical progression and decreased patient survival by univariate but not multivariate analysis.
https://ift.tt/2J3Shfb
Lasting Outcome Similar for ULS, SSLF for Pelvic Organ Prolapse
TUESDAY, April 17, 2018 -- For women with pelvic organ prolapse, there is no significant difference in five-year outcomes with uterosacral ligament suspension (ULS) and sacrospinous ligament fixation (SSLF) surgeries, and no difference in the...
https://ift.tt/2EUKq1d
Caffeine Does Not Appear to Be Linked to Risk of Arrhythmia
TUESDAY, April 17, 2018 -- Regular intake of coffee and tea does not appear to be associated with the risk of arrhythmia, according to a review published in the April 1 issue of JACC: Clinical Electrophysiology. Aleksandr Voskoboinik, M.B.B.S., from...
https://ift.tt/2qEzsbK
Calcium Channel Blockers May Up Pancreatic Cancer Risk in Women
TUESDAY, April 17, 2018 -- Use of short-acting calcium channel blockers (CCBs) is associated with increased risk of pancreatic cancer in postmenopausal women, according to a study presented at the annual meeting of the American Association for...
https://ift.tt/2EUJQ3q
USPSTF: Exercise Interventions Prevent Falls in Seniors
TUESDAY, April 17, 2018 -- The U.S. Preventive Services Task Force (USPSTF) concludes that exercise interventions may be beneficial for preventing falls in older adults; however, the evidence is insufficient to weigh the benefits and harms of...
https://ift.tt/2qEzrEI
2000 to 2015 Saw Increase in Institutional Post-Acute Care
TUESDAY, April 17, 2018 -- From 2000 to 2015 there was an increase in the use of institutional post-acute care, according to a study published in the April 17 issue of the Journal of the American Medical Association. Rachel M. Werner, M.D., Ph.D.,...
https://ift.tt/2ETpAPK
Neuraminidase as an influenza vaccine antigen: a low hanging fruit, ready for picking to improve vaccine effectiveness
Maryna C Eichelberger | David M Morens | Jeffery K Taubenberger
https://ift.tt/2Hr3dXh
Editorial overview: Innate immunity: The finely tuned STING of innate immunity
Gwendalyn J Randolph
https://ift.tt/2EUIvty
Meta‐analysis evaluating music interventions for anxiety and pain in surgery
British Journal of Surgery, EarlyView.
https://ift.tt/2EVgIZO
Randomized clinical trial of the effect of a fibrin sealant patch on pancreatic fistula formation after pancreatoduodenectomy
British Journal of Surgery, EarlyView.
https://ift.tt/2Hxe8yG
Mortality following surgery for trauma in an Indian trauma cohort
British Journal of Surgery, EarlyView.
https://ift.tt/2EURXx4
Effect of Oryctolagus cuniculus (rabbit) rennet on the texture, rheology, and sensory properties of white cheese
Food Science &Nutrition, EarlyView.
https://ift.tt/2H87o6P
Enhanced yield of oleuropein from olive leaves using ultrasound‐assisted extraction
Food Science &Nutrition, EarlyView.
https://ift.tt/2HpnDjt
Effect of sweet potato endogenous amylase activation on in vivo energy bioavailability and acceptability of soy‐enriched orange‐fleshed sweet potato complementary porridges
Food Science &Nutrition, EarlyView.
https://ift.tt/2J58aCa
Clinical significance of TM4SF1 as a tumor suppressor gene in gastric cancer
Cancer Medicine, EarlyView.
https://ift.tt/2qHVGJ5
Establishment of a nine‐gene prognostic model for predicting overall survival of patients with endometrial carcinoma
Cancer Medicine, EarlyView.
https://ift.tt/2H79s2V
Asymptomatic late-phase radiographic changes amongst chest wall patients are associated with a proton RBE exceeding 1.1
For matched proton and photon cohorts of chest-wall patients, asymptomatic late-phase radiographic changes within the lung were found to be significantly more prominent amongst those treated with protons. An en-face proton beam arrangement was used. RBE elevation could be attributable to either (i) the late, normal tissue endpoint considered, (ii) end-of-range proton LET elevation, or a combination of these two. Regardless, our results suggest that clinically-relevant proton RBEs exceed 1.1 under certain circumstances.
https://ift.tt/2H9YuG6
Definitive Radiation Therapy and Survival in Clinically Node-Positive Prostate Cancer
The survival benefit of combined radiation therapy and androgen deprivation therapy compared to androgen deprivation therapy alone for clinically lymph node-positive prostate cancer remains controversial. We identified clinically node-positive, non-metastatic prostate cancer patients from the Veterans Affairs system and compared mortality outcomes between treatment groups. We found that definitive treatment with radiation therapy improved prostate cancer-specific mortality and all-cause mortality, though only among patients with lower baseline prostate specific antigen.
https://ift.tt/2qEzr7F
Differential Association between Circulating Lymphocyte Populations with Outcome after Radiotherapy in Subtypes of Liver Cancer
This study investigated key effector and suppressor lymphocytes during radiotherapy in liver cancer patients. Results indicate that cellular immune responses may occur early during radiotherapy, associate with survival and significantly differ between histological subtypes. These data provide new insights for the pursuit of rational combinations of radiation with immunotherapy in liver cancer.
https://ift.tt/2Hcwy44
Blade‐Cast Nonfullerene Organic Solar Cells in Air with Excellent Morphology, Efficiency, and Stability
Advanced Materials, EarlyView.
https://ift.tt/2J6r8bJ
FeS2 Nanoparticles Decorated Graphene as Microbial‐Fuel‐Cell Anode Achieving High Power Density
Advanced Materials, EarlyView.
https://ift.tt/2HIb3cN
Optically Unraveling the Edge Chirality‐Dependent Band Structure and Plasmon Damping in Graphene Edges
Advanced Materials, EarlyView.
https://ift.tt/2J3SA9L
Anisotropic Broadband Photoresponse of Layered Type‐II Weyl Semimetal MoTe2
Advanced Materials, EarlyView.
https://ift.tt/2HHZlP9
Ion Gated Synaptic Transistors Based on 2D van der Waals Crystals with Tunable Diffusive Dynamics
Advanced Materials, EarlyView.
https://ift.tt/2J3PcMk
Dielectric Screening Meets Optimally Tuned Density Functionals
Advanced Materials, EarlyView.
https://ift.tt/2HJDCXm
2D Perovskites with Short Interlayer Distance for High‐Performance Solar Cell Application
Advanced Materials, EarlyView.
https://ift.tt/2HGcubp
High body mass index is associated with increased risk of treatment failure and surgery in biologic‐treated patients with ulcerative colitis
Alimentary Pharmacology &Therapeutics, EarlyView.
https://ift.tt/2H9eoEN
Three case reports of radiation-induced glioblastoma after complete remission of acute lymphoblastic leukemia
Abstract
Radiation therapy is sometimes performed to control intracranial acute lymphoblastic leukemia (ALL), but may lead to radiation-induced malignant glioma. The clinical, radiological, histological, and molecular findings are described of three cases of radiation-induced glioblastoma after the treatment for ALL. They received radiation therapy at age 6–8 years. The latency from radiation therapy to the onset of radiation-induced glioblastoma was 5–10 years. Magnetic resonance imaging demonstrated diffuse lesions with multiple small enhanced lesions in all cases. Histological examination showed that the tumors consisted of mainly small round astrocytic atypical cells in one case, and astrocytic atypical cells with elongated cytoplasm and nuclear pleomorphism with small cell component in two cases. Microvascular proliferation was present in all cases. Immunohistochemical analysis for B-Raf V600E, and mutational analysis for the isocitrate dehydrogenase (IDH) 1, IDH2, and H3F3A gene revealed the wild-type alleles in all three cases. The integrated diagnoses were IDH wild-type glioblastoma, and local irradiation and concomitant temozolomide were performed. After the initial treatment, significant shrinkage of the diffuse lesion and enhanced lesion was found in all cases. Radiation-induced glioblastoma occurring after the treatment for ALL had unique clinical, radiological, histological, and molecular characteristics in our three cases.
https://ift.tt/2H6CCPL
Immune‐mediated antitumor effect of a transplanted lymph node
International Journal of Cancer, EarlyView.
https://ift.tt/2HGZSRs
Distinct profiles of TERT promoter mutations and telomerase expression in head and neck cancer and cervical carcinoma
International Journal of Cancer, EarlyView.
https://ift.tt/2J5kHW2
1‐L‐MT, an IDO inhibitor, prevented colitis‐associated cancer by inducing CDC20 inhibition‐mediated mitotic death of colon cancer cells
International Journal of Cancer, EarlyView.
https://ift.tt/2HG8SWT
Time from breast cancer diagnosis to therapeutic surgery and breast cancer prognosis: A population‐based cohort study
International Journal of Cancer, EarlyView.
https://ift.tt/2HamnNN
A first-in-class inhibitor, MLN4924 (pevonedistat), induces cell-cycle arrest, senescence, and apoptosis in human renal cell carcinoma by suppressing UBE2M-dependent neddylation modification
Abstract
Purpose
MLN4924 is a second-generation inhibitor that targets ubiquitin–proteasome system by inhibiting neddylation activation enzyme (NAE), and subsequently blocking the neddylation-dependent activation of Cullin-RING E3 ligases (CRLs), which leads to the accumulation of CRLs substrates and hence, suppressing diverse tumor development. In this study, we investigated the potential application of this first-in-class inhibitor MLN4924 in the treatment of human renal cell carcinoma both in vitro and in vivo.
Methods
The impact of MLN4924 on renal cancer cells was determined by measuring viability (MTS), proliferation cell count test and clonogenic assays, cell cycle progression (flow cytometry with propidium iodide staining), apoptosis (flow cytometry with annexin V-FITC labeling) and DNA damage (immunofluorescent staining). The cell cycle regulatory molecules, apoptosis-related molecules, and cell stress-related proteins were examined by Western blotting. The influence of tumor cell migration was analyzed by wound healing assays. A well-established SCID xenograft mouse model was used to evaluate the effects of MLN4924 on tumor growth in vivo.
Results
The data showed that MLN4924 induced a dose-dependent cytotoxicity, anti-proliferation, anti-migration, and apoptosis in human renal cancer cells; and caused cell cycle arrested at the G2 phase. In addition, the E2 conjugating enzymes of Neddylation UBE2M played a major role in the proliferation control of renal cancer cells. Finally, we confirmed MLN4924 inhibited tumor growth in a RCC xenograft mouse model with minimal general toxicity.
Conclusion
We concluded that MLN4924 induces apoptosis and cell cycle arrest. These findings implied that MLN4924 provides a novel strategy for the treatment of RCC.
https://ift.tt/2EURfQa
Nut Consumption Associated With Reduced Risk of A-Fib
TUESDAY, April 17, 2018 -- Nut consumption is associated with reduced risk of atrial fibrillation, according to a study published online April 16 in Heart. Susanna C. Larsson, Ph.D., from the Karolinska Institutet in Stockholm, and colleagues...
https://ift.tt/2qGC4Fl
UTI Calculator Predicts Risk of Infant Urinary Tract Infection
TUESDAY, April 17, 2018 -- The newly developed UTICalc calculator can be used to guide testing and treatment in children with suspected urinary tract infection (UTI), according to a study published online April 16 in JAMA Pediatrics. In an effort to...
https://ift.tt/2qFApzX
Social Worker-Led Intervention Beneficial in Heart Failure
TUESDAY, April 17, 2018 -- A social worker-led palliative care intervention seems beneficial for patients with advanced heart failure at high risk for mortality, according to a study published online April 11 in JAMA Cardiology. Arden E. O'Donnell,...
https://ift.tt/2H5siY9
Metabolic Syndrome Common With Chronic Hep B Infection
TUESDAY, April 17, 2018 -- Metabolic syndrome (MetS) is prevalent among patients with chronic hepatitis B (HBV) infection, according to a study published online March 29 in Diabetes Care. Mandana Khalili, M.D., from the University of California, San...
https://ift.tt/2qHr3n5
Sedentary Habits Tied to Medial Temporal Lobe Thinning
TUESDAY, April 17, 2018 -- For non-demented middle-aged and older adults, there is an inverse correlation between medial temporal lobe (MTL) thickness and sedentary behavior, according to a study published online April 12 in PLOS ONE. Prabha...
https://ift.tt/2H8BoDN
Repeated BP Measures Linked to Drop in Initially Elevated BP
TUESDAY, April 17, 2018 -- Among patients with hypertension (HTN), repeated measurement of an initially elevated blood pressure (BP) is associated with a reduction in systolic BP, according to a research letter published online April 16 in JAMA...
https://ift.tt/2Hawvdm
Neuroscience Education, Motor Control Training Ease Spinal Pain
TUESDAY, April 17, 2018 -- For individuals with chronic spinal pain, pain neuroscience education combined with cognition-targeted motor control training seems more effective than current best-evidence physical therapy, according to a study published...
https://ift.tt/2H8Jn3P
Prognostic impact of perihepatic lymph node metastases in patients with resectable colorectal liver metastases
British Journal of Surgery, EarlyView.
https://ift.tt/2H6sdUq
Nationwide trends in the incidence and outcome of patients with gastrointestinal stromal tumour in the imatinib era
British Journal of Surgery, EarlyView.
https://ift.tt/2qBvArc
Generic velpatasvir plus sofosbuvir for hepatitis C virus infection in patients with or without human immunodeficiency virus coinfection
Alimentary Pharmacology &Therapeutics, EarlyView.
https://ift.tt/2qECBIJ
Real‐world use of elbasvir‐grazoprevir in patients with chronic hepatitis C: retrospective analyses from the TRIO network
Alimentary Pharmacology &Therapeutics, EarlyView.
https://ift.tt/2J235dU
Safety of sofosbuvir‐based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study
Alimentary Pharmacology &Therapeutics, EarlyView.
https://ift.tt/2HtQoLU
Paramedic receives positivity after being criticized for getting food
By EMS1 Staff LOUGHBOROUGH, England — A paramedic who tweeted about being criticized while getting food said he received a huge amount of support from the public. BBC reported that East Midlands Ambulance Service duty operations manager Tim Hargraves was making a food stop during a 10-hour shift when a stranger made a rude comment. "I had to wait for an ambulance, nice you have time to eat," ...
https://ift.tt/2J4ylsu
Positive Surgical Margins in Favorable-Stage Differentiated Thyroid Cancer
Objective: The significance of positive margin in favorable-stage well-differentiated thyroid cancer is controversial. We report outcomes of positive-margin patients with a matched-pair comparison to a negative-margin group. Materials and Methods: A total of 25 patients with classic-histology papillary or follicular carcinoma, total thyroidectomy +/− node dissection, stage T1-3N0-1bM0, positive surgical margin at primary site, adjuvant radioactive iodine (I-131), and age older than 18 years were treated between 2003 and 2013. Endpoints were clinical and biochemical (thyroglobulin-only) recurrence-free survival. Matched-pair analysis involved a 1:1 match with negative-margin cases matched for overall stage and I-131 dose. Results: Recurrence-free survival in positive-margin patients was 71% at 10 years. No patient was successfully salvaged with additional treatment. Only 1 patient died of thyroid cancer. Recurrence-free survival at 10 years was worse with a positive (71%) versus negative (90%) margin (P=0.140). Conclusions: Cure with a microscopically positive margin was suboptimal (71%) despite patients having classic-histology papillary and follicular carcinoma, favorable stage, and moderate-dose I-131 therapy. The authors declare no conflicts of interest. Reprints: Robert J. Amdur, MD, 2000 SW Archer Road, P.O. Box 100385, Gainesville, FL 32610-0385. E-mail: amdurr@shands.ufl.edu. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2ETWaRB
https://ift.tt/2ETWaRB
Long-term Outcomes With Ifosfamide-based Hypofractionated Preoperative Chemoradiotherapy for Extremity Soft Tissue Sarcomas
Objectives: The objective of this study was to analyze outcomes for patients with soft tissue sarcoma of the extremities using neoadjuvant ifosfamide-based chemotherapy and hypofractionated reduced dose radiotherapy, followed by limb-sparing surgery. Materials and Methods: An Institutional Review Board (IRB)-approved retrospective review of patients treated at a single institution between 1990 and 2013 was performed. In total, 116 patients were identified who received neoadjuvant ifosfamide-based chemotherapy and 28 Gy in 8 fractions of preoperative radiation (equivalent dose in 2 Gray fractions, 31.5 Gy [α/β 10] 36.4 Gy [α/β 3]) followed by limb-sparing surgery. Local recurrence (LR), distant failure (DF), and overall survival (OS) were calculated. Univariate and multivariate analysis for LR, DF, and OS were performed using Cox analysis. Statistical significance was set at a P
https://ift.tt/2ETHbal
https://ift.tt/2ETHbal
The Role of Provider Characteristics in the Selection of Surgery or Radiation for Localized Prostate Cancer and Association With Quality of Care Indicators
Introduction: We sought to identify the role of provider and facility characteristics in receipt of radical prostatectomy (RP) or external beam radiation therapy (EBRT) and adherence to quality of care measures in men with localized prostate cancer (PCa). Materials and Methods: Subjects included 2861 and 1630 men treated with RP or EBRT, respectively, for localized PCa whose records were reabstracted as part of the Centers for Disease Control and Prevention Breast and Prostate Patterns of Care Study. We utilized multivariable generalized estimating equation regression analysis to assess patient, clinical, and provider (year of graduation, urologist density) and facility (group vs. solo, academic/teaching status, for-profit status, distance to treatment facility) characteristics that predicted use of RP versus EBRT as well as quality of care outcomes. Results: Multivariable analysis revealed that group (vs. solo) practice was associated with a decreased risk of RP (odds ratio, 0.47; 95% confidence interval, 0.25-0.91). Among RP patients with low-risk disease, receipt of a bone scan that was not recommended was significantly predicted by race and insurance status. Surgical quality of care measures were associated with physician's year of graduation and receiving care at a teaching facility. Conclusions: In addition to demographic factors, we found that provider and facility characteristics were associated with treatment choice and specific quality of care measures. Long-term follow-up is required to determine whether quality of care indicators are related to PCa outcomes. The Breast and Prostate Cancer Data Quality and Patterns of Care Study was supported by the Centers for Disease Control and Prevention through cooperative agreements with the California Cancer Registry (Public Health Institute) (1-U01-DP000260), Emory University (1-U01-DP000258), Louisiana State University Health Sciences Center (1-U01-DP000253), Minnesota Cancer Surveillance System (Minnesota Department of Health) (1-U01-DP000259), Medical College of Wisconsin (1-U01-DP000261), University of Kentucky (1-U01-DP000251), and Wake Forest University (1-U01-DP000264). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. The authors declare no conflicts of interest. Reprints: Ann S. Hamilton, PhD, Keck School of Medicine of University of Southern California, 2001 N. Soto St 318E, MC9239, Los Angeles, CA 90089-9239. E-mail: ahamilt@med.usc.edu. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2JUP6Yr
https://ift.tt/2JUP6Yr
Fabricating High-viscosity Droplets using Microfluidic Capillary Device with Phase-inversion Co-flow Structure
https://ift.tt/2HFOPrE
BCR‐ABL enhances the prolyl isomerase activity of Pin 1 by interacting with DAPK1 in ph+ ALL
Cancer Medicine, EarlyView.
https://ift.tt/2JQTtns
Chloroquine‐treated dendritic cells require STAT1 signaling for their tolerogenic activity
European Journal of Immunology, EarlyView.
https://ift.tt/2vmyA0j
Tetramer‐based identification of naïve antigen‐specific B cells within a polyclonal repertoire
European Journal of Immunology, EarlyView.
https://ift.tt/2HvtiUR
The CXCL5/CXCR2 axis contributes to the epithelial-mesenchymal transition of nasopharyngeal carcinoma cells by activating ERK/GSK-3β/snail signalling
Abstract
Background
Distant metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear.
Methods
Quantitative RT-PCR (qRT-PCR), western blotting, cell growth, foci formation, migration and invasion assays, and xenograft mouse models were utilized to examine the expression levels and functions of the CXCL5/CXCR2 axis in NPC. A luciferase reporter assay, western blotting, immunofluorescence, and migration and invasion assays were used to identify and verify the ERK/GSK-3β/Snail signalling pathway.
Results
CXCL5 was significantly increased in the sera of NPC patients, and high expression levels of CXCL5/CXCR2 in NPC primary tissues indicated poor survival. CXCL5 and CXCR2 were upregulated in NPC cell lines. Ectopic expression of the CXCL5/CXCR2 axis promoted NPC cell migration and invasion in vitro and the formation of lung metastases in vivo. Mechanistically, the dual overexpression of CXCL5 and CXCR2 promoted cell spreading by inducing the epithelial-mesenchymal transition (EMT) through the activation of the ERK/GSK-3β/Snail signalling pathway.
Conclusion
The CXCL5/CXCR2 axis contributes to the EMT of NPC cells by activating ERK/GSK-3β/Snail signalling, and this axis may be a potential diagnostic marker and therapeutic target for patients with NPC.
https://ift.tt/2H6sQNC
A retrospective study on the crestal bone loss associated with different implant surfaces in chronic periodontitis patients under maintenance
Clinical Oral Implants Research, EarlyView.
https://ift.tt/2HH8OGl
Correction to: Sepsis increases perioperative metastases in a murine model
It has been highlighted that the original manuscript [1] contains a typesetting error in Fig. 1 and the Fig. 1c panel gas been inadvertently duplicated in panel Fig. 1d. This does not affect the results and conclusions of the article. The correct version of Fig. 1 is included with this Correction. The original article has been updated.
https://ift.tt/2J3AJzO
Peritoneal carcinomatosis arising from rectal or colonic adenocarcinoma treated with cytoreductive surgery (CRS) hyperthermic intraperitoneal chemotherapy (HIPEC): two different diseases
Abstract
Purpose
Peritoneal carcinomatosis (PC) from colorectal cancer (CRC) has poor survival. Multi-modal treatment including systemic chemotherapy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) can be used in selected patients with curative intent. The majority published works consider PC of CRC origin as a homogenous disease. Aim of this study is to stress the different biological behaviors and survival of PC according to colonic or rectal origin.
Methods
Data of CRS and HIPEC procedures for PC of CRC origin performed at MD Anderson Cancer Center-Madrid (Spain) have been collected, dividing patients into two groups according to colonic or rectal PC. Clinical, operatory, and postoperatory variables of the two groups have been analyzed to compare survival-related rates and PC origin.
Results
In the years 2004–2015, 114 procedures of CRS followed by HIPEC for peritoneal metastasis of different origin have been performed; of these, 36 procedures were for colorectal PC (31 patients in colonic and 5 in rectal group). Two groups are homogenous after analysis of clinical, operatory, and follow-up data. Median survival (OS) is significantly higher in colonic compared to rectal group (47.83 vs. 22.0 months, p 0.008). 3- and 5-year survival rate is 74 and 50% in colonic group vs. 20 and 0% in rectal group.
Conclusion
Rectal origin PC has a more aggressive behavior compared to colonic origin, reflecting in a worst prognosis of patients affected by rectal origin PC. According to our data and literature, indications of multi-modal treatment including CRS and HIPEC should be more restrictive for rectal cancer PC. Authors should differentiate colonic and rectal origin of PC when reporting cases in the literature.
https://ift.tt/2HMcl6F
In Situ Self‐Assembling Micellar Depots that Can Actively Trap and Passively Release NO with Long‐Lasting Activity to Reverse Osteoporosis
Advanced Materials, EarlyView.
https://ift.tt/2H6c4OO
On the optimal z -score threshold for SISCOM analysis to localize the ictal onset zone
Abstract
Background
In epilepsy patients, SISCOM or subtraction ictal single photon emission computed tomography co-registered to magnetic resonance imaging has become a routinely used, non-invasive technique to localize the ictal onset zone (IOZ). Thresholding of clusters with a predefined number of standard deviations from normality (z-score) is generally accepted to localize the IOZ. In this study, we aimed to assess the robustness of this parameter in a group of patients with well-characterized drug-resistant epilepsy in whom the exact location of the IOZ was known after successful epilepsy surgery. Eighty patients underwent preoperative SISCOM and were seizure free in a postoperative period of minimum 1 year. SISCOMs with z-threshold 2 and 1.5 were analyzed by two experienced readers separately, blinded from the clinical ground truth data. Their reported location of the IOZ was compared with the operative resection zone. Furthermore, confidence scores of the SISCOM IOZ were compared for the two thresholds.
Results
Visual reporting with a z-score threshold of 1.5 and 2 showed no statistically significant difference in localizing correspondence with the ground truth (70 vs. 72% respectively, p = 0.17). Interrater agreement was moderate (κ = 0.65) at the threshold of 1.5, but high (κ = 0.84) at a threshold of 2, where also reviewers were significantly more confident (p < 0.01).
Conclusions
SISCOM is a clinically useful, routinely used modality in the preoperative work-up in many epilepsy surgery centers. We found no significant differences in localizing value of the IOZ using a threshold of 1.5 or 2, but interrater agreement and reader confidence were higher using a z-score threshold of 2.
https://ift.tt/2vm97UK
Issue highlights
British Journal of Clinical Pharmacology, Volume 84, Issue 5, Page 811-812, May 2018.
https://ift.tt/2HaPgZV
Issue Information
British Journal of Clinical Pharmacology, Volume 84, Issue 5, Page 809-810, May 2018.
https://ift.tt/2HGqeDb
Large differences in neonatal drug use between NICUs are common practice: time for consensus?
British Journal of Clinical Pharmacology, EarlyView.
https://ift.tt/2HaPekL
Immediate implant replacement with DIEP flap: a single-stage salvage option in failed implant-based breast reconstruction
Abstract
Background
Implant-based immediate breast reconstruction after skin-sparing mastectomy has shown a significant improvement in patients' quality of life, making the procedure steadily more popular year after year. However, this technique has a high morbidity rate, including skin necrosis and implant exposure.
Methods
A retrospective review of a prospectively held database for autologous breast reconstruction in our institution of the last 5 years found eight cases with exposed implants after nipple-sparing mastectomy and immediate reconstruction. A single-stage procedure consisting on implant removal and immediate replacement with a deepithelialized DIEP flap was performed in all cases (10 DIEP flaps).
Results
All flaps were successful. Patients' mean age was 45 years old. Three patients developed seroma (5, 7, and 14 days after surgery, respectively). No infections were detected in up to 24 months of follow-up.
Conclusions
Nipple-sparing mastectomy with immediate implant-based reconstruction is considered oncologically safe. However, it has a high rate of complications that could require implant removal. Immediate free flap reconstruction is a feasible and safe option to replace the missing volume with low risk of complications that result in a soft and natural-shaped breast.
https://ift.tt/2EXGUmQ
The versatile role of exosomes in cancer progression: diagnostic and therapeutic implications
Abstract
Background
Recent advances in cancer biology have highlighted the relevance of exosomes and nanovesicles as carriers of genetic and biological messages between cancer cells and their immediate and/or distant environments. It has been found that these molecular cues may play significant roles in cancer progression and metastasis. Cancer cells secrete exosomes containing diverse molecules that can be transferred to recipient cells and/or vice versa to induce a plethora of biological processes, including angiogenesis, metastasis formation, therapeutic resistance, epithelial-mesenchymal transition and epigenetic/stemness (re)programming. While exosomes interact with cells within the tumour microenvironment to promote tumour growth, these vesicles can also facilitate the process of distant metastasis by mediating the formation of pre-metastatic niches. Next to their tumour promoting effects, exosomes have been found to serve as potential tools for cancer diagnosis and therapy. The ease of isolating exosomes and their content from different body fluids has led to the identification of diagnostic and prognostic biomarker signatures, as well as to predictive biomarker signatures for therapeutic responses. Exosomes can also be used as cargos to deliver therapeutic anti-cancer drugs, and they can be engineered to serve as vaccines for immunotherapy. Additionally, it has been found that inhibition of exosome secretion, and thus the transfer of oncogenic molecules, holds promise for inhibiting tumour growth. Here we provide recent information on the diverse roles of exosomes in various cellular and systemic processes governing cancer progression, and discuss novel strategies to halt this progression using exosome-based targeted therapies and methods to inhibit exosome secretion and the transfer of pro-tumorigenic molecules.
Conclusions
This review highlights the important role of exosomes in cancer progression and its implications for (non-invasive) diagnostics and the development of novel therapeutic strategies, as well as its current and future applications in clinical trials.
https://ift.tt/2qGpgyL
Hereditary pancreatitis in Paediatrics: the causative role of p.Leu104Pro mutation of cationic trypsinogen gene also in young subjects
We read with interest the letter by Németh et al,1 describing a hereditary pancreatitis (HP) family of Hungarian origin carrying the heterozygous p.Leu104Pro variant of human cationic trypsinogen (PRSS1) gene. It added further data to previous publications by Schnúr et al2 and Balázs et al,3 who proposed that a subset of PRSS1 variants caused chronic pancreatitis by inducing misfolding and endoplasmic reticulum stress, rather than increased intrapancreatic trypsin activity.
However, a clinically defined relationship between the mutation and the phenotypic expression in the general population still remains to be established. Indeed, to date, p.Leu104Pro PRSS1 variant has been reported in three families: three heterozygous carriers of a German pedigree without clinically proven chronic pancreatitis, a subject of Chinese origin with late onset idiopathic chronic pancreatitis3 4 and three related Hungarian subjects who presented with HP in adult life, as reported in...
https://ift.tt/2qHi45l
Ledipasvir/sofosbuvir with or without ribavirin for 8 or 12 weeks for the treatment of HCV genotype 4 infection: results from a randomised phase III study in Egypt
Objective
We evaluated the efficacy and safety of ledipasvir/sofosbuvir alone and with ribavirin for 8 and 12 weeks in Egyptian patients with and without cirrhosis, who were infected with hepatitis C virus (HCV) genotype 4, including those who had failed previous treatment with sofosbuvir regimens.
DesignIn this open-label, multicentre, phase III study, treatment-naive patients were randomised to receive 8 or 12 weeks of ledipasvir/sofosbuvir±ribavirin. Interferon treatment-experienced patients were randomised to receive 12 weeks of ledipasvir/sofosbuvir±ribavirin, while sofosbuvir-experienced or ledipasvir/sofosbuvir-experienced patients received 12 weeks of ledipasvir/sofosbuvir+ribavirin. Randomisation was stratified by cirrhosis status. The primary endpoint was sustained virological response 12 weeks post-treatment (SVR12).
ResultsWe enrolled 255 patients from four centres in Egypt. Among treatment-naive patients, SVR12 rates were 95% and 90% for those receiving 8 weeks of ledipasvir/sofosbuvir alone and with ribavirin, respectively, and 98% for those receiving 12 weeks of ledipasvir/sofosbuvir both alone and with ribavirin. Among interferon-experienced patients, SVR rates were 94% for those receiving 12 weeks of ledipasvir/sofosbuvir and 100% for those receiving 12 weeks of ledipasvir/sofosbuvir plus ribavirin. All patients previously treated with sofosbuvir regimens who received ledipasvir/sofosbuvir plus ribavirin achieved SVR12. The most common adverse events, headache and fatigue, were more common among patients receiving ribavirin.
ConclusionAmong non-cirrhotic treatment-naive patients with HCV genotype 4, 8 weeks of ledipasvir/sofosbuvir±ribavirin was highly effective. Twelve weeks of ledipasvir/sofosbuvir±ribavirin was highly effective regardless of presence of cirrhosis or prior treatment experience, including previous treatment with sofosbuvir or ledipasvir/sofosbuvir.
Trial registration numberNCT02487030.
https://ift.tt/2H8ya3a
Fatty Acid 13C Isotopologue Profiling Provides Insight into Trophic Carbon Transfer and Lipid Metabolism of Invertebrate Consumers
The fatty acid trophic marker approach, i.e., the assimilation of fatty acids as entire molecule and transfer into consumer tissue with no or minor modification, is hampered by knowledge gaps in fatty acid metabolism of small soil invertebrates. Isotopologue profiling is provided as a valuable tool to disentangle trophic interactions.
https://ift.tt/2HIkx7U
An HS-MRM Assay for the Quantification of Host-cell Proteins in Protein Biopharmaceuticals by Liquid Chromatography Ion Mobility QTOF Mass Spectrometry
https://ift.tt/2H8yMlc
Prophylactic thyroidectomy in children with multiple endocrine neoplasia type 2
British Journal of Surgery, EarlyView.
https://ift.tt/2HxUXEP
Prognostic value of pathological node status after neoadjuvant radiotherapy for rectal cancer
British Journal of Surgery, EarlyView.
https://ift.tt/2IZqY5N
Prognostic significance of gross extrathyroidal extension invading only strap muscles in differentiated thyroid carcinoma
British Journal of Surgery, EarlyView.
https://ift.tt/2HxfR6U
Mortality in patients with permanent hypoparathyroidism after total thyroidectomy
British Journal of Surgery, EarlyView.
https://ift.tt/2J4dW7c
Multicentre phase II trial of near‐infrared imaging in elective colorectal surgery
British Journal of Surgery, EarlyView.
https://ift.tt/2Hu3LLK
Predictors of complications after direct‐to‐implant breast reconstruction with an acellular dermal matrix from a multicentre randomized clinical trial
British Journal of Surgery, EarlyView.
https://ift.tt/2J4e1aV
Two‐year results of the randomized clinical trial DILALA comparing laparoscopic lavage with resection as treatment for perforated diverticulitis
British Journal of Surgery, EarlyView.
https://ift.tt/2HxfLw4
Interobserver variability in the classification of appendicitis during laparoscopy
British Journal of Surgery, EarlyView.
https://ift.tt/2J3mMBW
An extended OpenSim knee model for analysis of strains of connective tissues
OpenSim musculoskeletal models provide an accurate simulation environment that eases limitations of in vivo and in vitro studies. In this work, a biomechanical knee model was formulated with femoral articular ...
https://ift.tt/2HtM1As
Simulation of phase contrast angiography for renal arterial models
With the development of versatile magnetic resonance acquisition techniques there arises a need for more advanced imaging simulation tools to enable adequate image appearance prediction, measurement sequence d...
https://ift.tt/2J2oxzh
Learn about stress and mental health with CrewCare
You Are Invited Join us April 19th to learn how the CrewCare project is a vital resource in understanding how stress plays a role in the lives of crew members, organizations and the first responder industry. CrewCare was created in response to growing concerns about mental health. ImageTrend and the collaborative minds behind the project are committed to making a positive impact on the daily struggles ...
https://ift.tt/2H6pDhd
Characterization of biosurfactant from yeast using residual soybean oil under acidic conditions and their use in metal removal processes
Abstract
This study aimed at the production of biosurfactants from yeasts under acidic conditions using residual soybean oil as a carbon source, as well as the biosurfactant produced in the solubilization of metals in sewage sludge. The yeast Meyerozyma guilliermondii was considered the best producer in both pH 4.0 and 2.0, therefore the product obtained by this yeast was characterized by Fourier Transform Infrared (FT-IR) and 1H Nuclear Magnetic Resonance (NMR) spectroscopy. Moreover, it was applied in metal removal assays in anaerobic sewage sludge. The spectra obtained in FT-IR suggested that M. guilliermondii's biosurfactant had a similar structure to glycolipids from the sophorolipid class and it was confirmed by 1H NMR spectroscopy. In the bioleaching assays, the application of biosurfactant (2%) produced by M. guilliermondii with pH adjusted to 2.0 was able to solubilize 15.9% of cadmium from the sewage sludge.https://ift.tt/2JUG4Li
Publishing activities improves undergraduate biology education
Abstract
To improve undergraduate biology education, there is an urgent need for biology instructors to publish their innovative active learning instructional materials in peer-reviewed journals. To do this, instructors can measure student knowledge about a variety of biology concepts, iteratively design activities, explore student learning outcomes, and publish the results. Creating a set of well-vetted activities, searchable through a journal interface, saves other instructors time and encourages the use of active-learning instructional practices. For authors, these publications offer new opportunities to collaborate and can provide evidence of a commitment to using active-learning instructional techniques in the classroom.https://ift.tt/2vlOoQR
Mechanisms of bacterial attachment to roots
Abstract
The attachment of bacteria to roots constitutes the first physical step in many plant-microbe interactions. These interactions exert both positive and negative influences on agricultural systems depending on whether a growth-promoting, symbiotic, or pathogenic relationship transpires. A common biphasic mechanism of root attachment exists across agriculturally important microbial species, including Rhizobium, Agrobacterium, Pseudomonas, Azospirillum and Salmonella. Attachment studies have revealed how plant-microbe interactions develop, and how to manipulate these relationships for agricultural benefit. Here, we review our current understanding of the molecular mechanisms governing plant-microbe root attachment and draw together a common biphasic model.https://ift.tt/2qFsSRn
Examining the effectiveness of consuming flour made from agronomically biofortified wheat (Zincol-2016/NR-421) for improving Zn status in women in a low-resource setting in Pakistan: study protocol for a randomised, double-blind, controlled cross-over trial (BiZiFED)
Introduction
Dietary zinc (Zn) deficiency is a global problem, particularly in low-income and middle-income countries where access to rich, animal-source foods of Zn is limited due to poverty. In Pakistan, Zn deficiency affects over 40% of the adult female population, resulting in suboptimal immune status and increased likelihood of complications during pregnancy.
Methods and analysisWe are conducting a double-blind, randomised controlled feeding study with cross-over design in a low-resource setting in Pakistan. Households were provided with flour milled from genetically and agronomically biofortified grain (Zincol-2016/NR-421) or control grain (Galaxy-2013). Fifty households were recruited. Each household included a woman aged 16–49 years who is neither pregnant nor breastfeeding, and not currently consuming nutritional supplements. These women were the primary study participants. All households were provided with control flour for an initial 2-week baseline period, followed by an 8-week intervention period where 25 households receive biofortified flour (group A) and 25 households receive control flour (group B). After this 8-week period, groups A and B crossed over, receiving control and biofortified flour respectively for 8 weeks. Tissue (blood, hair and nails) have been collected from the women at five time points: baseline, middle and end of period 1, and middle and end of period 2.
Ethics and disseminationEthical approval was granted from the lead university (reference no. STEMH 697 FR) and the collaborating institution in Pakistan. The final study methods (including any modifications) will be published in peer-reviewed journals, alongside the study outcomes on completion of the data analysis. In addition, findings will be disseminated to the scientific community via conference presentations and abstracts and communicated to the study participants through the village elders at an appropriate community forum.
Registration detailsThe trial has been registered with the ISRCTN registry, study ID ISRCTN83678069.
https://ift.tt/2qD0m3D
Associations of smoking and alcohol consumption with healthy ageing: a systematic review and meta-analysis of longitudinal studies
Objectives
The number of older people is growing across the world; however, quantitative synthesis of studies examining the impact of lifestyle factors on the ageing process is rare. We conducted a systematic review and meta-analysis of longitudinal studies to synthesise the associations of smoking and alcohol consumption with healthy ageing (HA).
MethodsMajor electronic databases were searched from inception to March 2017 (prospectively registered systematic reviews registration number CRD42016038130). Studies were assessed for methodological quality. Random-effect meta-analysis was performed to calculate pooled ORs and 95% CI.
ResultsIn total, we identified 28 studies (n=184 543); 27 studies reported results on smoking, 22 on alcohol consumption. 23 studies reported a significant positive association of never or former smoking with HA and 4 non-significant. 12 studies reported a significant positive association of alcohol consumption with HA, 9 no association and 1 negative. Meta-analysis revealed increased pooled OR of HA for never smokers compared with current smokers (2.36, 95% CI 2.03 to 2.75), never smokers compared with former smokers (1.32, 95% CI 1.23 to 1.41), former or never smokers compared with current smokers (1.72, 95% CI 1.20 to 2.47), never smokers compared with past or current smokers (1.29, 95% CI 1.16 to 1.43); drinkers compared with non-drinkers (1.28, 95% CI 1.08 to 1.52), light drinkers compared with non-drinkers (1.12, 95% CI 1.03 to 1.22), moderate drinkers compared with non-drinkers (1.35, 95% CI 0.93 to 1.97) and high drinkers compared with non-drinkers (1.25, 95% CI 1.09 to 1.44). There was considerable heterogeneity in the definition and measurement of HA and alcohol consumption.
ConclusionsThere is consistent evidence from longitudinal studies that smoking is negatively associated with HA. The associations of alcohol consumption with HA are equivocal. Future research should focus on the implementation of a single metric of HA, on the use of consistent drinking assessment among studies and on a full-range of confounding adjustment. Our research also highlighted the limited research on ageing in low-and-middle-income countries.
https://ift.tt/2qGWLAK
The French prospective multisite registry on sudden unexpected infant death (OMIN): rationale and study protocol
Introduction
Even after 'back-to-sleep' campaigns, sudden unexpected infant death (SUID) continues to be the leading cause of death for infants 1 month to 1 year old in developed countries, with devastating social, psychological and legal implications for families. To sustainably tackle this problem and decrease the number of SUIDs, a French SUID registry was initiated in 2015 to (1) inform prevention with standardised data, (2) understand the mechanisms leading to SUID and the contribution of the already known or newly suggested risk factors and (3) gather a multidisciplinary group of experts to coordinate and develop innovative and urgent research in the SUID area.
Methods and analysisThis observational multisite prospective observatory includes all cases of sudden unexpected deaths in children younger than 2 years occurring in the French territory covered by the 35 participating French referral centres. From these cases, various data concerning sociodemographic conditions, death scene, personal and family medical history, parental behaviours, sleep environment, clinical examinations, biological and imagery investigations and autopsy are systematically collected. These data will be complemented as of 2018 with a biobank of diverse biological samples (blood, hair, urine, faeces and cerebrospinal fluid), with other administrative health-related data (health claim reimbursements and hospital admissions) and socioenvironmental data. Insights from exploratory descriptive statistics and thematic analysis will be combined for the design of targeted strategies to effectively reduce preventable infant deaths.
Ethics and disseminationThe French sudden unexpected infant death registry (Observatoire National des Morts Inattendues du Nourrisson registry;OMIN) was approved in 2015 by the French Data Protection Authority in clinical research (Commission Nationale de l'Informatique et des Libertés: number 915273) and by an independent ethics committee (Groupe Nantais d'Ethique dans le Domaine de la Santé: number 2015-01-27). Results will be discussed with associations of families affected by SUID, caregivers, funders of the registry, medical societies and researchers and will be submitted to international peer-reviewed journals and presented at international conferences.
https://ift.tt/2qDsZO7
Prognostic value of ki67 in BCG-treated non-muscle invasive bladder cancer: a meta-analysis and systematic review
Objectives
The aim of this study was to explore the prognostic value of ki67 as a marker in patients with non-muscle invasive bladder cancer (NMIBC) treated with BCG.
MethodsStudies were systematically retrieved from the relevant databases (Web of Science, PubMed, Cochrane Library and Embase), and the expiry date was May 2017. The research steps referred to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement.
ResultsA total of 11 studies that complied with the inclusion criteria were included. The expression of ki67 was not statistically significantly associated with recurrence-free survival (RFS) (HR 1.331; 95% CI 0.980 to 1.809). No significant heterogeneity was found among all included studies (I2=36.7%, p=0.148). The expression of ki67 was statistically significantly associated with progression-free survival (PFS) (HR 2.567; 95% CI 1.562 to 4.219), and the overexpression of ki67 was the risk factor for PFS. Significant heterogeneity was noted among all the included studies (I2=55.6%, p=0.021). The studies that might cause heterogeneity were excluded using the Galbraith plot, and then the meta-analysis was performed again. The results showed that the expression of ki67 was still associated with PFS (HR 2.922; 95% CI 2.002 to 4.266).
ConclusionsThe overexpression of ki67 was the risk factor for PFS, and the relationship between the expression of ki67 and RFS was not statistically significant in patients with NMIBC treated with BCG intravesical immunotherapy. Well-designed, prospective, with a large sample size are still needed to validate the findings.
https://ift.tt/2J5d7Lf
Study protocol for the SARON trial: a multicentre, randomised controlled phase III trial comparing the addition of stereotactic ablative radiotherapy and radical radiotherapy with standard chemotherapy alone for oligometastatic non-small cell lung cancer
Introduction
Following growing evidence to support the safety, local control (LC) and potential improvement in overall survival (OS) in patients with oligometastatic non-small cell lung cancer (NSCLC) that have been treated with local ablative therapy such as stereotactic ablative radiotherapy (SABR) and stereotactic radiosurgery (SRS), we initiate the SARON trial to investigate the impact and feasibility of adding SABR/SRS and radical radiotherapy (RRT) following standard chemotherapy on OS.
Methods and analysisSARON is a large, randomised controlled, multicentre, phase III trial for patients with oligometastatic EGFR, ALK and ROS1 mutation negative NSCLC (1–3 sites of synchronous metastatic disease, one of which must be extracranial). 340 patients will be recruited over 3 years from approximately 30 UK sites and randomised to receive either standard platinum-doublet chemotherapy only (control arm) or standard chemotherapy followed by RRT/SABR to their primary tumour and then SABR/SRS to all other metastatic sites (investigational arm). The primary endpoint is OS; the study is powered to detect an improvement in median survival from 9.9 months in the control arm to 14.3 months in the investigational arm with 85% power and two-sided 5% significance level. The secondary endpoints are LC, progression-free survival, new distant metastasis-free survival, toxicity and quality of life. An early feasibility review will take place after 50 randomised patients. Patients requiring both conventional thoracic RT to the primary and SABR to a thoracic metastasis will be included in a thoracic SABR safety substudy to assess toxicity and planning issues in this subgroup of patients more thoroughly.
Ethics and disseminationAll participants are given a SARON patient information sheet and required to give written informed consent. Results will be submitted for presentation at local and international conferences and expected to be published in a peer-reviewed journal.
Trial registration number Sponsor referenceUCL/13/0594.
https://ift.tt/2HwlRge
Preventing emergency department (ED) visits and hospitalisations of older adults with cognitive impairment compared with the general senior population: what do we know about avoidable incidents? Results from a scoping review
Objectives
Older cognitively impaired adults present a higher risk of hospitalisation and mortality following a visit to the emergency department (ED). Better understanding of avoidable incidents is needed to prevent them and the associated ED presentations in community-dwelling adults. This study aimed to synthetise the actual knowledge concerning these incidents leading this population to ED presentation, as well as possible preventive measures to reduce them.
DesignA scoping review was performed according to the Arksey and O'Malley framework.
MethodsScientific and grey literature published between 1996 and 2017 were examined in databases (Medline, Cumulative Index of Nursing and Allied Health, Ageline, Scopus, ProQuest Dissertations/theses, Evidence-based medecine (EBM) Reviews, Healthstar), online library catalogues, governmental websites and published statistics. Sources discussing avoidable incidents leading to ED presentations were included and then extended to those discussing hospitalisation and mortality due to a lack of sources. Data (type, frequency, severity and circumstances of incidents, preventive measures) was extracted using a thematic chart, then analysed with content analysis.
Results67 sources were included in this scoping review. Five types of avoidable incidents (falls, burns, transport accidents, harm due to self-negligence and due to wandering) emerged, and all but transport accidents were more frequent in cognitively impaired seniors. Differences regarding circumstances were only reported for burns, as scalding was the most prevalent mechanism of injury for this population compared with flames for the general senior population. Multifactorial interventions and implications of other professionals (eg, pharmacist, firefighters) were reported as potential interventions to reduce avoidable incidents. However, few preventive measures were specifically tested in this population.
ConclusionsPrimary research that screens for cognitive impairment and involves actors (eg, paramedics) to improve our understanding of avoidable incidents leading to ED visits is greatly needed. This knowledge is essential to develop preventive measures tailored to the needs of older cognitively impaired adults.
https://ift.tt/2H6HAYF
Last Year of Life Study Cologne (LYOL-C): protocol for a cross-sectional mixed methods study to examine care trajectories and transitions in the last year of life until death
Introduction
The last year of life constitutes a particularly vulnerable phase for patients, involving nearly all health and social care structures. Yet, little scientific evidence is available that provides insight into the trajectories including the number and types of care setting transitions, transitions into palliative care and the dying phase. Only few studies have focused on difficulties associated with having to move between health and social care settings in the last year of life, although patients face a significant risk of adverse events. The Last Year of Life Study Cologne (LYOL-C) aims to fill this gap.
Methods and analysisLYOL-C is a mixed-methods study composed of four steps: (1) Claims data collected by the statutory health insurance funds of deceased persons will be analysed with regard to patient care trajectories, health service transitions and costs in the last year of life. (2) Patient trajectories and transitions in healthcare will additionally be reconstructed by analysing the retrospective accounts of bereaved relatives (n=400) using a culturally adapted version of the Views of Informal Carers—Evaluation of Services Short Form questionnaire and the Patient Assessment of Care for Chronic Conditions Short Form questionnaire adapted for relatives. (3) Qualitative interviews with bereaved relatives (n=40–60) will provide in-depth insight into reasons for transitions and effects on patients' quality of life. (4) Focus groups (n=3–5) with Healthcare Professionals will be conducted to discuss challenges associated with transitions in the last year of life.
Ethics and disseminationEthical approval has been obtained from the Ethics Commission of the Faculty of Medicine of Cologne University (#17–188). Results will be submitted for publication in peer-reviewed journals and presented at national and international conferences.
Trial registration numberThe study is registered in the German Clinical Trials Register (DRKS00011925) and in the Health Services Research Database (VfD_CoRe-Net_17_003806).
https://ift.tt/2HtCucE
Does dexmedetomidine given as a premedication or intraoperatively reduce post-hospitalisation behaviour change in children? A study protocol for a randomised controlled trial in a tertiary paediatric hospital
Introduction
It has been reported that post-hospitalisation behaviour change (PHBC) occurs in over 50% of children undergoing a general anaesthetic and manifests as behaviours such as sleep and eating disorders, defiance of authority, nightmares, enuresis and temper tantrums. The effect is usually short-lived (2–4 weeks); however, in 5–10% of children, these behaviours can last up to 12 months. The risk factors for developing PHBC include underlying anxiety in the child or parent, a previous bad hospital experience, emergence delirium and preschool age. A recent meta-analysis of alpha-2 agonists (including dexmedetomidine) found that they effectively reduce the incidence of emergence delirium but none of the studies looked at longer term outcomes, such as PHBC.
Methods and analysisTwo-year-old to seven-year-old children requiring general anaesthesia for common day-case procedures will be randomly assigned to one of three groups: a dexmedetomidine pre medication group, an intraoperative dexmedetomidine group and a control group. Baseline anxiety levels of the parent will be recorded and the anxiety of the child during induction of anaesthesia will also be recorded using validated tools. The primary outcome will be negative behaviours after hospitalisation and these will be measured using the Post Hospitalisation Behaviour Questionnaire for Ambulatory Surgery and the Strengths and Difficulties Questionnaire. These questionnaires will be administered by a blinded researcher at days 3, 14 and 28 post surgery.
Ethics and disseminationEthics approval has been granted by the Children's Health Queensland human research ethics committee (HREC/15/QRCH/248) and the University of Queensland human research ethics office (#2016001715). Any amendments to this protocol will be submitted to the ethics committees for approval.
Trial registration numberANZCTR:12616000096459; Pre-results.
https://ift.tt/2H8id8O
Domains of health-related quality of life in age-related macular degeneration: a qualitative study in the Chinese cultural context
Objective
To explore which areas of health-related quality of life were affected in Chinese patients, and to identify whether the areas are well covered by validated questionnaires.
DesignA qualitative study based on semistructured interviews was conducted. A qualitative thematic analysis following the approach of Colaizzi was used to analyse the interview data for significant statements and phrases. The themes and subthemes organised from the analysis were then compared by using the following current instruments: National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), Macular Disease Quality of life Questionnaire (MacDQoL) and Low-Luminance Questionnaire (LLD).
Participants and settingTwenty-one patients with age-related macular degeneration were recruited from the eye clinic of Southwest Eye Hospital in Chongqing, mainland China.
ResultsThe mean age of the participants was 69.8 years (range 57–82 years) and the duration of the disease ranged from 3 months to 6 years. The qualitative analysis revealed nine important domains including symptoms, difficulties with daily activities, depending on others, depression and uncertainty, optimism and hope, social isolation, role change, family support and financial burden. However, all the three questionnaires were insufficient to capture the full extent of quality of life issues of Chinese patients with AMD, and MacDQoL covered more domains when compared with NEI-VFQ-25 and LLD.
ConclusionThe domains of concepts important to people with AMD in the Chinese culture are not fully represented in the three widely used questionnaires. Nine important domains were identified for the assessment of quality of life and should be considered when assessing the impact of AMD on Chinese individuals. Further studies are needed to develop an AMD quality of life questionnaire, better tailored to the needs and culture of Chinese patients.
https://ift.tt/2HxPZrT
Doctors on the move: a European case study on the key characteristics of national recertification systems
Objectives
With increased cross-border movement, ensuring safe and high-quality healthcare has gained primacy. The purpose of recertification is to ensure quality of care through periodically attesting doctors' professional proficiency in their field. Professional migration and facilitated cross-border recognition of qualifications, however, make us question the fitness of national policies for safeguarding patient care and the international accountability of doctors.
Design and settingWe performed document analyses and conducted 19 semistructured interviews to identify and describe key characteristics and effective components of 10 different European recertification systems, each representing one case (collective case study). We subsequently compared these systems to explore similarities and differences in terms of assessment criteria used to determine process quality.
ResultsGreat variety existed between countries in terms and assessment formats used, targeting cognition, competence and performance (Miller's assessment pyramid). Recertification procedures and requirements also varied significantly, ranging from voluntary participation in professional development modules to the mandatory collection of multiple performance data in a competency-based portfolio. Knowledge assessment was fundamental to recertification in most countries. Another difference concerned the stakeholders involved in the recertification process: while some systems exclusively relied on doctors' self-assessment, others involved multiple stakeholders but rarely included patients in assessment of doctors' professional competence. Differences between systems partly reflected different goals and primary purposes of recertification.
ConclusionRecertification systems differ substantially internationally with regard to the criteria they apply to assess doctors' competence, their aims, requirements, assessment formats and patient involvement. In the light of professional mobility and associated demands for accountability, we recommend that competence assessment includes patients' perspectives, and recertification practices be shared internationally to enhance transparency. This can help facilitate cross-border movement, while guaranteeing high-quality patient care.
https://ift.tt/2H8chwR
Systematic review and meta-analysis of diabetes mellitus, cardiovascular and respiratory condition epidemiology in sexual minority women
Objective
Sexual minority women (SMW) experience higher chronic disease risk factors than heterosexual counterparts. However, it was unclear if these risks translate into higher physical condition rates. This systematic review evaluates cardiovascular disease (CVD), hypertension, respiratory disease and diabetes mellitus in SMW.
MethodsA protocol was registered with the Prospero database (CRD42016050299). Included were studies reporting mortality, incidence or prevalence of the above-listed conditions in SMW compared with heterosexual women. Databases (platforms) searched from 2010 to December 2016 were Medline (Ovid), Embase (Elsevier), Cumulative Index to Nursing and Allied Health Literature (Elsevier), PsycINFO (Ovid), Social Policy and Practice (Ovid), Cochrane CENTRAL (Cochrane Library), Science Citation Index (Web of Science), and CAB Abstracts (Ovid). Search terms included Medical Subject Heading (MeSH) terms and text words. Extensive additional searches were conducted in specialist academic journals and websites. Two reviewers checked study eligibility. One independently extracted data and assessed quality, checked by a second reviewer, with disagreements resolved through discussion. The Critical Appraisal Skills Programme cohort checklist was used to assess risk of bias. Meta-analysis was conducted where more than four studies reported the same outcomes, with Comprehensive Meta-Analysis software, using adjusted ORs (AORs) and random-effects models. Heterogeneity was assessed using I2 test.
ResultsIdentified were 23 103 citations, 692 full texts screened and 16 studies included (in 18 papers). One reported mortality (from Denmark), none incidence and 15 prevalence (14 USA, 1 Australia). Same-sex cohabiting women had higher mortality rates compared with opposite-sex cohabiting women in CVD (HR=1.37 (95% CI 1.22 to 1.54)) and respiratory disease (HR=2.10 (95% CI 1.74 to 2.53)). AOR meta-analyses of seven studies showed higher asthma rates in lesbians (OR=1.44 (95% CI 1.27 to 1.64), I2=0%) and bisexual women (OR=1.64 (95% CI 1.41 to 1.89), I2=0%) but no differences for CVD (5 studies), hypertension (5 studies) or diabetes mellitus (7 studies).
ConclusionsThese new health estimates require further confirmatory epidemiological studies, and investigation into potential environmental, hormonal, physiological, psychological or genetic causes. This would be supported by routine collection of sexual identity measures in population-level epidemiological surveys.
https://ift.tt/2H6KQHJ
Competencies necessary for becoming a leader in the field of community medicine: a Japanese qualitative interview study
Objectives
To clarify competencies for inclusion in our curriculum that focuses on developing leaders in community medicine.
DesignQualitative interview study.
SettingAll six regions of Japan, including urban and rural areas.
ParticipantsNineteen doctors (male: 18, female: 1) who play an important leadership role in their communities participated in semistructured interviews (mean age 48.3 years, range 34–59; mean years of clinical experience 23.1 years, range 9–31).
MethodSemistructured interviews were held and transcripts were independently analysed and coded by the first two authors. The third and fourth authors discussed and agreed or disagreed with the results to give a consensus agreement. Doctors were recruited by maximum variation sampling until thematic saturation was achieved.
ResultsSix themes emerged: (1)'Medical ability': includes psychological issues and difficult cases in addition to basic medical problems. High medical ability gives confidence to other medical professionals. (2)'Long term perspective': the ability to develop a long-term, comprehensive vision and to continuously work to achieve the vision. Cultivation of future generations of doctors is included. (3) 'Team building':the ability to drive forward programmes that include residents and local government workers, to elucidate a vision, to communicate and to accept other medical professionals. (4)'Ability to negotiate': the ability to negotiate with others to ensure that programmes and visions progress smoothly (5) 'Management ability': the ability to run a clinic, medical unit or medical association. (6) 'Enjoying oneself': doctors need to feel an attraction to community medicine, that it be fun and challenging for them.
ConclusionsWe found six competencies that are needed by leaders in the field of community medicine. The results of this study will contribute to designing a curriculum that develops such leaders.
https://ift.tt/2H8f3Ca
Increase in assisted suicide in Switzerland: did the socioeconomic predictors change? Results from the Swiss National Cohort
Objective
To determine whether the strong increase in assisted suicides in Switzerland since 2008 is linked to a shift in the socioeconomic factors associated with assisted suicide and its related diagnoses.
MethodsIn a population-based longitudinal study, we investigated assisted suicides in Switzerland over the period 2003–2014. Two groups of younger (25–64 years) and older (65–94 years) persons were analysed separately and compared. We calculated crude rates and used Cox proportional hazard and logistic regression models to examine associations of assisted dying with gender, marital status, education, religion, neighbourhood socioeconomic status and other variables, and investigated trends over time.
ResultsWe identified 3941 assisted suicides among 6 237 997 Swiss residents, 80% of which occurred in the older age group. Crude rates of assisted suicide more than tripled during the study period from 3.60 to 11.21 per 100 000 person-years; the increase was more pronounced in the older age group. Cancer was the most common underlying diagnosis (41.8%), but the percentage dying assisted was highest among patients with diseases of the nervous system (5.25% in the younger and 1.23% in the older age group). The factors associated with assisted suicide did not change during the study period. Female gender, higher education, having no religious affiliation, no children and a Swiss passport, living in a neighbourhood with a higher socioeconomic index and living in the French-speaking part of Switzerland were associated with a higher rate.
ConclusionsThe study results do not indicate any shift in socioeconomic factors associated with assisted suicide, but a more pronounced increase in incidence among the elderly.
https://ift.tt/2HrkHTd
Medical overuse in the Iranian healthcare system: a systematic review protocol
Introduction
Lack of resources is one of the main problems of all healthcare systems. Recent studies have shown that reducing the overuse of medical services plays an important role in reducing healthcare system costs. Overuse of medical services is a major problem in the healthcare system, and it threatens the quality of the services, can harm patients and create excess costs for patients. So far, few studies have been conducted in this regard in Iran. The main objective of this systematic review is to perform an inclusive search for studies that report overuse of medical services in the Iranian healthcare system.
Method and analysisAn extensive search of the literature will be conducted in six databases including PubMed, Embase, Scopus, Web of Science, Cochrane and Scientific Information Database using a comprehensive search strategy to identify studies on overuse of medical care. The search will be done without time limit until the end of 2017, completed by reference tracking, author tracking and expert consultation. The search will be conducted on 1 February 2018. Any study that reports an overuse in a service based on a specific standard will be included in the study. Two reviewers will screen the articles based on the title, abstract and full text, and extract data about type of service, clinical area and overuse rate. Quality appraisal will be assessed using the Joanna Briggs Institute checklist. Potential discrepancies will be resolved by consulting a third author.
Ethics and disseminationRecommendations will be made to the Iranian MOHME (Ministry of Health and Medical Education) in order to make better evidence-based decisions about medical services in the future.
PROSPERO registration numberCRD42017075481
https://ift.tt/2H8eRmq
Understanding students and clinicians experiences of informal interprofessional workplace learning: an Australian qualitative study
Objectives
While postgraduate studies have begun to shed light on informal interprofessional workplace learning, studies with preregistration learners have typically focused on formal and structured work-based learning. The current study investigated preregistration students' informal interprofessional workplace learning by exploring students' and clinicians' experiences of interprofessional student-clinician (IPSC) interactions.
DesignA qualitative interview study using narrative techniques was conducted.
SettingStudent placements across multiple clinical sites in Victoria, Australia.
ParticipantsThrough maximum variation sampling, 61 participants (38 students and 23 clinicians) were recruited from six professions (medicine, midwifery, nursing, occupational therapy, paramedicine and physiotherapy).
MethodsWe conducted 12 group and 10 individual semistructured interviews. Themes were identified through framework analysis, and the similarities and differences in subthemes by participant group were interrogated.
ResultsSix themes relating to four research questions were identified: (1) conceptualisations of IPSC interactions; (2) context for interaction experiences; (3) the nature of interaction experiences; (4) factors contributing to positive or negative interactions; (5) positive or negative consequences of interactions and (6) suggested improvements for IPSC interactions. Seven noteworthy differences in subthemes between students and clinicians and across the professions were identified.
ConclusionsDespite the results largely supporting previous postgraduate research, the findings illustrate greater breadth and depth of understandings, experiences and suggestions for preregistration education. Educators and students are encouraged to seek opportunities for informal interprofessional learning afforded by the workplace.
https://ift.tt/2qGWPR0
Adoption of a novel surgical innovation into clinical practice: protocol for a qualitative systematic review examining surgeon views
Introduction
Efficient adoption of clinically effective novel surgical innovations has great potential benefits for patients. Factors affecting the adoption of surgical innovation are not well understood and proposed models of adoption do not accurately correlate with historical evidence. This protocol is for a systematic review that aims to identify the qualitative evidence relating to surgeon views regarding the adoption of novel surgical innovation into clinical practice.
Methods and analysisA systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance will be performed. Two independent reviewers will search the following databases: MEDLINE, Embase, Science Direct, Scopus, Web of Science and the Cochrane Library of Systematic Reviews. Inclusion criteria are studies which report on the views of surgeons who adopt a novel surgical innovation into clinical practice. Each article will be screened for inclusion and assessed according to a Critical Appraisal Skills Programme tool. Data will be synthesised and analysed according to thematic analysis. Given the anticipated yield of a small heterogeneous body of evidence meeting the eligibility criteria for the review, a narrative-based summary is planned.
Ethics and disseminationThis review does not require formal ethical approval as it does not involve direct patient contact or patient-identifiable data. The results of this review will be published in a peer-reviewed journal and presented at relevant conferences. The results will also inform an empirical qualitative study exploring surgeon and other stakeholder views regarding the introduction of novel surgical technology and procedures into clinical practice.
PROSPERO registration numberCRD42017076715.
https://ift.tt/2HxLcqb
Patient safety climate in general public hospitals in China: differences associated with department and job type based on a cross-sectional survey
Objective
This study analysed differences in the perceived patient safety climate among different working departments and job types in public general hospitals in China.
DesignCross-sectional survey.
SettingEighteen tertiary hospitals and 36 secondary hospitals from 10 areas in Shanghai, Hubei Province and Gansu Province, China.
ParticipantsOverall, 4753 staff, including physicians, nurses, medical technicians and managers, were recruited from March to June 2015.
Main outcome measureThe Patient Safety Climate in Healthcare Organisations (PSCHO) tool and the percentages of 'problematic responses' (PPRs) were used as outcome measures. Multivariable two-level random intercept models were applied in the analysis.
ResultsA total of 4121 valid questionnaires were collected. Perceptions regarding the patient safety climate varied among departments and job types. Physicians responded with relatively more negative evaluations of 'organisational resources for safety', 'unit recognition and support for safety efforts', 'psychological safety', 'problem responsiveness' and overall safety climate. Paediatrics departments, intensive care units, emergency departments and clinical auxiliary departments require more attention. The PPRs for 'fear of blame and punishment' were universally significantly high, and the PPRs for 'fear of shame' and 'provision of safe care' were remarkably high, especially in some departments. Departmental differences across all dimensions and the overall safety climate primarily depended on job type.
ConclusionsThe differences suggest that strategies and measures for improving the patient safety climate should be tailored by working department and job type.
https://ift.tt/2H8ex7c
MiR‐21 improves invasion and migration of drug‐resistant lung adenocarcinoma cancer cell and transformation of EMT through targeting HBP1
Cancer Medicine, EarlyView.
https://ift.tt/2HttzYK
Hepatitis B infection reported with cancer chemotherapy: analyzing the US FDA Adverse Event Reporting System
Cancer Medicine, EarlyView.
https://ift.tt/2J5749J
Congenital heart diseases and cardiovascular abnormalities in 22q11.2 deletion syndrome: From well‐established knowledge to new frontiers
American Journal of Medical Genetics Part A, EarlyView.
https://ift.tt/2HGHWq4
Medical expenses of urban Chinese patients with stomach cancer during 2002–2011: a hospital-based multicenter retrospective study
Abstract
Background
In China, stomach cancer is the third most common cancer and the third leading cause of cancer death. Few studies have examined Chinese stomach cancer patients' medical expenses and their associated trends. The Cancer Screening Program in Urban China (CanSPUC) is a Major Public Health Project funded by the central government. Through this project, we have extracted patients' medical expenses from hospital billing data to examine the costs of the first course treatments (which refers to 2 months before and 10 months after the date of cancer diagnosis) in Chinese patients with stomach cancer and the associated trends.
Methods
The expense data of 14,692 urban Chinese patients with stomach cancer were collected from 40 hospitals in 13 provinces. We estimated the inflation-adjusted medical expenses per patient during 2002–2011. We described the time trends of medical expenses at the country-level, and those trends by subgroup, and analyzed the compositions of medical expenses. We constructed the Generalized Linear Mixed (GLM) regression model with Poisson distribution to examine the factors that were associated with medical expenses per patient.
Results
The average medical expenses of the first course treatments were about 43,249 CNY (6851 USD) in 2011, more than twice of that in 2002. The expenses increased by an average annual rate of 7.4%. Longer stay during hospitalization and an increased number of episodes of care are the two main contributors to the expense increase. The upward trend of medical expenses was observed in almost all patient subgroups. Drug expenses accounted for over half of the medical expenses.
Conclusions
The average medical expenses of the first course (2 months before and 10 months after the date of cancer diagnosis) treatments per stomach cancer patient in urban China in 2011 were doubled during the previous 10 years, and about twice as high as the per capita disposable income of urban households in the same year. Such high expenses indicate that it makes economic sense to invest in cancer prevention and control in China.
https://ift.tt/2HGQa1j
The oncogenic effects of HES1 on salivary adenoid cystic carcinoma cell growth and metastasis
Abstract
Background
Our previous study demonstrated a close relationship between NOTCH signaling pathway and salivary adenoid cystic carcinoma (SACC). HES1 is a well-known target gene of NOTCH signaling pathway. The purpose of the present study was to further explore the molecular mechanism of HES1 in SACC.
Methods
Comparative transcriptome analyses by RNA-Sequencing (RNA-Seq) were employed to reveal NOTCH1 downstream gene in SACC cells. Immunohistochemical staining was used to detect the expression of HES1 in clinical samples. After HES1-siRNA transfected into SACC LM cells, the cell proliferation and cell apoptosis were tested by suitable methods; animal model was established to detect the change of growth ability of tumor. Transwell and wound healing assays were used to evaluate cell metastasis and invasion.
Results
We found that HES1 was strongly linked to NOTCH signaling pathway in SACC cells. The immunohistochemical results implied the high expression of HES1 in cancerous tissues. The growth of SACC LM cells transfected with HES1-siRNAs was significantly suppressed in vitro and tumorigenicity in vivo by inducing cell apoptosis. After HES1 expression was silenced, the SACC LM cell metastasis and invasion ability was suppressed.
Conclusions
The results of this study demonstrate that HES1 is a specific downstream gene of NOTCH1 and that it contributes to SACC proliferation, apoptosis and metastasis. Our findings serve as evidence indicating that HES1 may be useful as a clinical target in the treatment of SACC.
https://ift.tt/2J5w94h
Circumstances of SUDEP: A nationwide population‐based case series
Epilepsia, EarlyView.
https://ift.tt/2J6ouTo
Studies with Ray Guillery on the early development of the visual pathways: eyecup, optic nerve, chiasm and optic tract
European Journal of Neuroscience, EarlyView.
https://ift.tt/2H5vfYZ
One year of experience using the Paris System for Reporting Urinary Cytology
Cancer Cytopathology, EarlyView.
https://ift.tt/2qFo9iB
Is pathology prepared for the adoption of artificial intelligence?
Cancer Cytopathology, EarlyView.
https://ift.tt/2H6yvDn
Prevalence, identification of virulence factors, O-serogroups and antibiotic resistance properties of Shiga-toxin producing Escherichia coli strains isolated from raw milk and traditional dairy products
Shiga-toxigenic Escherichia coli strains are one of the most important foodborne bacteria with an emergence of antibiotic resistance. Foodborne STEC strains are mainly associated with presence of certain virulenc...
https://ift.tt/2qJHkIr
Associations of cigarette smoking and alcohol drinking with stomach cancer survival: A prospective patient cohort study in Japan
International Journal of Cancer, EarlyView.
https://ift.tt/2qGX6DF
Higher carbohydrate intake is associated with increased risk of all‐cause and disease‐specific mortality in head and neck cancer patients: results from a prospective cohort study
International Journal of Cancer, EarlyView.
https://ift.tt/2H4VxKF
Notch signals modulate lgl mediated tumorigenesis by the activation of JNK signaling
Oncogenic potential of Notch signaling and its cooperation with other factors to affect proliferation are widely established. Notch exhibits a cooperative effect with loss of a cell polarity gene, scribble to ind...
https://ift.tt/2J3turF
Under diagnosis of intestinal schistosomiasis in a referral hospital, North Ethiopia
The present cross-sectional study was aimed at determining the magnitude of under diagnosis of intestinal schistosomiasis among patients requested for routine ova/parasite examination at Ayder referral hospital.
https://ift.tt/2Hqdumq
Homology modelling, molecular docking, and molecular dynamics simulations reveal the inhibition of Leishmania donovani dihydrofolate reductase-thymidylate synthase enzyme by Withaferin-A
Present in silico study was carried out to explore the mode of inhibition of Leishmania donovani dihydrofolate reductase-thymidylate synthase (Ld DHFR-TS) enzyme by Withaferin-A, a withanolide isolated from Witha...
https://ift.tt/2H65TWK
Idiopathic basal ganglia calcification associated with cerebral micro-infarcts: a case report
Idiopathic basal ganglia calcification (IBGC) is a rare neurodegenerative disorder characterized by symmetric intracranial calcium deposition. We report a patient with IBGC associated with cerebral infarction ...
https://ift.tt/2vpz59S
The cold pressor test in interictal migraine patients – different parasympathetic pupillary response indicates dysbalance of the cranial autonomic nervous system
Data on autonomic nervous system (ANS) activations in migraine patients are quite controversial, with previous studies reporting over- and underactivation of the sympathetic as well as parasympathetic nervous ...
https://ift.tt/2qEZD21
Perceptions of risk of infertility among male survivors of childhood cancer: A report from the Childhood Cancer Survivor Study
Cancer, EarlyView.
https://ift.tt/2H64I9M
Patient Protection and Affordable Care Act Medicaid expansion and gains in health insurance coverage and access among cancer survivors
Cancer, EarlyView.
https://ift.tt/2HGp8r7
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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