Publication date: Available online 30 March 2018
Source:Injury
Author(s): Gowri Shivasabesan, Biswadev Mitra, Gerard M. O'Reilly
BackgroundTrauma registries play an integral role in trauma systems but their valid use hinges on data quality. The aim of this study was to determine, among contemporary publications using trauma registry data, the level of reporting of data completeness and the methods used to deal with missing data.MethodsA systematic review was conducted of all trauma registry-based manuscripts published from 01 January 2015 to current date (17 March 2017). Studies were identified by searching MEDLINE, EMBASE, and CINAHL using relevant subject headings and keywords. Included manuscripts were evaluated based on previously published recommendations regarding the reporting and discussion of missing data. Manuscripts were graded on their degree of characterization of such observations. In addition, the methods used to manage missing data were examined.ResultsThere were 539 manuscripts that met inclusion criteria. Among these, 208 (38.6%) manuscripts did not mention data completeness and 88 (16.3%) mentioned missing data but did not quantify the extent. Only a handful (n = 26; 4.8%) quantified the 'missingness' of all variables. Most articles (n = 477; 88.5%) contained no details such as a comparison between patient characteristics in cohorts with and without missing data. Of the 331 articles which made at least some mention of data completeness, the method of managing missing data was unknown in 34 (10.3%). When method(s) to handle missing data were identified, 234 (78.8%) manuscripts used complete case analysis only, 18 (6.1%) used multiple imputation only and 34 (11.4%) used a combination of these.ConclusionMost manuscripts using trauma registry data did not quantify the extent of missing data for any variables and contained minimal discussion regarding missingness. Out of the studies which identified a method of managing missing data, most used complete case analysis, a method that may bias results. The lack of standardization in the reporting and management of missing data questions the validity of conclusions from research based on trauma registry data.
https://ift.tt/2GEFulR
Παρασκευή 30 Μαρτίου 2018
Missing Data in Trauma Registries: A Systematic Review
Performance of the modified TRISS for evaluating trauma care in subpopulations: a cohort study
Publication date: Available online 30 March 2018
Source:Injury
Author(s): Leonie de Munter, Suzanne Polinder, Daan Nieboer, Koen W.W. Lansink, Ewout W. Steyerberg, Mariska A.C. de Jongh
IntroductionPrevious research showed that there is no agreement on a practically applicable model to use in the evaluation of trauma care. A modification of the Trauma and Injury Severity Score (modified TRISS) is used to evaluate trauma care in the Netherlands. The aim of this study was to evaluate the prognostic ability of the modified TRISS and to determine where this model needs improvement for better survival predictions.MethodsPatients were included if they were registered in the Brabant Trauma Registry from 2010 through 2015. Missing values were imputed according to multiple imputation. Subsets were created based on age, length of stay, type of injury and injury severity. Probability of survival was calculated with the modified TRISS. Discrimination was assessed with the Area Under the Receiver Operating Curve (AUROC). Calibration was studied graphically.ResultsThe AUROC was 0.84 (95% CI: 0.83, 0.85) for the total cohort (N = 69,747) but only 0.53 (95% CI: 0.51, 0.56) for elderly patients with hip fracture. Overall, calibration of the modified TRISS was adequate for the total cohort, with an overestimation for elderly patients and an underestimation for patients without brain injury.ConclusionsOutcome comparison conducted with TRISS-based predictions should be interpreted with care. If possible, future research should develop a simple prediction model that has accurate survival prediction in the aging overall trauma population (preferable with patients with hip fracture), with readily available predictors.
https://ift.tt/2IinNWC
Clinician tasking in ambulance control improves the identification of major trauma patients and pre-hospital critical care team tasking
Publication date: Available online 30 March 2018
Source:Injury
Author(s): Neil Sinclair, Paul A. Swinton, Michael Donald, Lisa Curatolo, Peter Lindle, Steph Jones, Alasdair R. Corfield
IntroductionTrauma remains the fourth leading cause of death in western countries and is the leading cause of death in the first four decades of life. NICE guidance in 2016 advocated the attendance of pre-hospital critical care trauma team (PHCCT) in the pre-hospital stage of the care of patients with major trauma. Previous publications support dispatch by clinicians who are also actively involved in the delivery of the PHCCT service; however there is a lack of objective outcome measures across the current reviewed evidence base. In this study, we aimed to assess the accuracy of PHCCT clinician led dispatch, when measured by Injury Severity Score (ISS).MethodsA retrospective cohort study over a 2 year period pre and post implementation of a PHCCT clinician led dispatch of PHCCT for potential major trauma patients, using national ambulance data combined with national trauma registry data.ResultsA total of 99,702 trauma related calls were made to SAS including 495 major trauma patients with an ISS >15, and a total of 454 dispatches of a PHCCT. Following the introduction of a PHCCT clinician staffed trauma desk, the sensitivity for major trauma was increased from 11.3% to 25.9%. The difference in sensitivity between the pre and post trauma desk group was significant at 14.6% (95% CI 7.4%–21.4%, p < 0.001).DiscussionThe results from the study support the results from other studies recommending that a PHCCT clinician should be located in ambulance control to identify major trauma patients as early as possible and co-ordinate the response.
https://ift.tt/2GHBH7m
Impact of timing on soft tissue augmentation during implant treatment: A systematic review and meta‐analysis
Clinical Oral Implants Research, EarlyView.
https://ift.tt/2pTS5Ya
Anti‐thymocyte globulin improves survival free from relapse and graft‐versus‐host disease after allogeneic peripheral blood stem cell transplantation in patients with Philadelphia‐negative acute lymphoblastic leukemia: An analysis by the Acute Leukemia Working Party of the EBMT
Cancer, EarlyView.
https://ift.tt/2IkuIyz
HOTAIR gene polymorphisms contribute to increased neuroblastoma susceptibility in Chinese children
Cancer, EarlyView.
https://ift.tt/2GlSgq1
A Translational Model of Incomplete Catch‐Up Growth: Early‐Life Hypoxia and the Effect of Physical Activity
Clinical and Translational Science, EarlyView.
https://ift.tt/2Ih2JQe
Postconditioning effects of argon or xenon on early graft function in a porcine model of kidney autotransplantation
British Journal of Surgery, EarlyView.
https://ift.tt/2GZuoWj
Pain management for patients with cancer
CA: A Cancer Journal for Clinicians, EarlyView.
https://ift.tt/2GF6eTo
Optimal pain management for patients with cancer in the modern era
CA: A Cancer Journal for Clinicians, EarlyView.
https://ift.tt/2Gr36ax
Identification of Proteins Required for Precise Positioning of Apc2 in Dendrites
In Drosophila neurons, uniform minus-end-out polarity in dendrites is maintained in part by kinesin-2-mediated steering of growing microtubules at branch points. Apc links the kinesin motor to growing microtubule plus ends and Apc2 recruits Apc to branch points where it functions. Because Apc2 acts to concentrate other steering proteins to branch points, we wished to understand how Apc2 is targeted. From an initial broad candidate RNAi screen, we found Miro (a mitochondrial transport protein), Ank2, Axin, spastin and Rac1 were required to position Apc2-GFP at dendrite branch points. YFP-Ank2-L8, Axin-GFP and mitochondria also localized to branch points suggesting the screen identified relevant proteins. By performing secondary screens, we found that energy production by mitochondria was key for Apc2-GFP positioning and spastin acted upstream of mitochondria. Ank2 seems to act independently from other players, except its membrane partner, Neuroglian (Nrg). Rac1 likely acts through Arp2/3 to generate branched actin to help recruit Apc2-GFP. Axin can function in a variety of wnt signaling pathways, one of which includes heterotrimeric G proteins and Frizzleds. Knockdown of Gas, Gao, Fz and Fz2, reduced targeting of Apc2 and Axin to branch points. Overall our data suggest that mitochondrial energy production, Nrg/Ank2, branched actin generated by Arp2/3 and Fz/G proteins/Axin function as four modules that control localization of the microtubule regulator Apc2 to its site of action in dendrite branch points.
https://ift.tt/2J5UaJ8
Genome-Wide Analysis of Mycoplasma bovirhinis GS01 Reveals Potential Virulence Factors and Phylogenetic Relationships
Mycoplasma bovirhinis is a significant etiology in bovine pneumonia and mastitis, but our knowledge about the genetic and pathogenic mechanisms of M. bovirhinis is very limited. In this study, we sequenced the complete genome of M. bovirhinis strain GS01 isolated from the nasal swab of pneumonic calves in Gansu, China, and we found that its genome forms a 847,985 bp single circular chromosome with a GC content of 27.57% and with 707 protein-coding genes. The putative virulence determinants of M. bovirhinis were then analyzed. Results showed that three genomic islands and 16 putative virulence genes, including one adhesion gene enolase, seven surface lipoproteins, proteins involved in glycerol metabolism, and cation transporters, might be potential virulence factors. Glycerol and pyruvate metabolic pathways were defective. Comparative analysis revealed remarkable genome variations between GS01 and a recently reported HAZ141_2 strain, and extremely low homology with others mycoplasma species. Phylogenetic analysis demonstrated that M. bovirhinis was most genetically close to M. canis, distant from other bovine Mycoplasma species. Genomic dissection may provide useful information on the pathogenic mechanisms and genetics of M. bovirhinis.
https://ift.tt/2pTMIrK
Genome-Wide Association Mapping Uncovers Fw1, a Dominant Gene Conferring Resistance to Fusarium Wilt in Strawberry
Fusarium wilt, a soil-borne disease caused by the fungal pathogen Fusarium oxysporum f. sp. fragariae, threatens strawberry (Fragaria x ananassa) production worldwide. The spread of the pathogen, coupled with disruptive changes in soil fumigation practices, have greatly increased disease pressure and the importance of developing resistant cultivars. While resistant and susceptible cultivars have been reported, a limited number of germplasm accessions have been analyzed, and contradictory conclusions have been reached in earlier studies to elucidate the underlying genetic basis of resistance. Here, we report the discovery of Fw1, a dominant gene conferring resistance to Fusarium wilt in strawberry. The Fw1 locus was uncovered in a genome-wide association study of 565 historically and commercially important strawberry accessions genotyped with 14,408 SNP markers. Fourteen SNPs in linkage disequilibrium with Fw1 physically mapped to a 2.3 Mb segment on chromosome 2 in a diploid F. vesca reference genome. Fw1 and 11 tightly linked GWAS-significant SNPs mapped to linkage group 2C in octoploid segregating populations. The most significant SNP explained 85% of the phenotypic variability and predicted resistance in 97% of the accessions tested-broad-sense heritability was 0.96. Several disease resistance and defense-related gene homologs, including a small cluster of genes encoding nucleotide-binding leucine-rich-repeat proteins, were identified in the 0.7 Mb genomic segment predicted to harbor Fw1. DNA variants and candidate genes identified in the present study should facilitate the development of high-throughput genotyping assays for accurately predicting Fusarium wilt phenotypes and applying marker-assisted selection.
https://ift.tt/2J6cwtG
A Whole Genome Assembly of the Horn Fly, Haematobia irritans, and Prediction of Genes with Roles in Metabolism and Sex Determination
Haematobia irritans, commonly known as the horn fly, is a globally distributed blood-feeding pest of cattle that is responsible for significant economic losses to cattle producers. Chemical insecticides are the primary means for controlling this pest but problems with insecticide resistance have become common in the horn fly. To provide a foundation for identification of genomic loci for insecticide resistance and for discovery of new control technology, we report the sequencing, assembly, and annotation of the horn fly genome. The assembled genome is 1.14 Gb, comprising 76,616 scaffolds with N50 scaffold length of 23 Kb. Using RNA-Seq data, we have predicted 34,413 gene models of which 19,185 have been assigned functional annotations. Comparative genomics analysis with the Dipteran flies Musca domestica L., Drosophila melanogaster, and Lucilia cuprina, show that the horn fly is most closely related to M. domestica, sharing 8,748 orthologous clusters followed by D. melanogaster and L. cuprina, sharing 7,582 and 7,490 orthologous clusters respectively. We also identified a gene locus for the sodium channel protein in which mutations have been previously reported that confers target site resistance to the most common class of pesticides used in fly control. Additionally, we identified 276 genomic loci encoding members of metabolic enzyme gene families such as cytochrome P450s, esterases and glutathione S-transferases, and several genes orthologous to sex determination pathway genes in other Dipteran species.
https://ift.tt/2pTMDUY
Loss of NF-{kappa}B1 Promotes Inflammation and Immune Checkpoint Regulators [Research Watch]
Polymorphisms that reduce NF-B1 in epithelial and hematopoietic cells promote gastric cancer.
https://ift.tt/2pU7Rms
Increasing Fc{gamma}R Binding Activity May Enhance Anti-CTLA4 Efficacy [Research Watch]
Anti-CTLA4 antibodies induce an FcR-dependent depletion of Tregs to promote tumor rejection.
https://ift.tt/2IelQub
Inhibiting PTPN12-Regulated RTKs May Be Therapeutic in TNBC [Research Watch]
PTPN12 deficiency may confer sensitivity to tyrosine kinase inhibitor combinations in TNBC.
https://ift.tt/2pRKzgX
LHPP Is a Histidine Phosphatase and a Tumor Suppressor [Research Watch]
Deregulated histidine phosphorylation may promote tumorigenesis in hepatocellular carcinoma (HCC).
https://ift.tt/2uzyZvR
Machine Learning Improves Diagnosis of CNS Cancers [News in Brief]
Algorithm spots patterns in genome-wide methylation profiles to help classify brain and spinal cord tumors.
https://ift.tt/2pSpzH8
Retraction: ‘Sunlight exposure is important for preventing hip fractures in patients with Alzheimer's disease, Parkinson's disease, or stroke’ by J. Iwamoto, T. Takeda and H. Matsumoto
Acta Neurologica Scandinavica, EarlyView.
https://ift.tt/2GlD501
SMAD4 gene mutation renders pancreatic cancer resistance to radiotherapy through promotion of autophagy
Purpose: Understanding the mechanism of radioresistance could help develop strategies to improve therapeutic response of patients with PDAC. The SMAD4 gene is frequently mutated in pancreatic cancer. In this study, we investigated the role of SMAD4 deficiency in pancreatic cancer cells' response to radiotherapy. Experimental Design: We downregulated SMAD4 expression with SMAD4 siRNA or SMAD4 shRNA and overexpressed SMAD4 in SMAD4 mutant pancreatic cancer cells followed by clonogenic survival assay to evaluate their effects on cell radioresistance. To study the mechanism of radioresistance, the effects of SMAD4 loss on reactive oxygen species (ROS) and autophagy were determined by Flow Cytometry and immunoblot analysis, respectively. Furthermore, we measured radioresistance by clonogenic survival assay after treatment with autophagy inhibitor (Chloroquine) and ROS inhibitor (N-acetyl-L-cysteine) in SMAD4-depleted pancreatic cancer cells. Finally, the effects of SMAD4 on radioresistance were also confirmed in an orthotopic tumor model derived from SMAD4-depleted Panc-1 cells. Results: SMAD4-depleted pancreatic cancer cells were more resistant to radiotherapy based on clonogenic survival assay. Overexpression of wild type SMAD4 in SMAD4-mutant cells rescued their radiosensitivity. Radioresistance mediated by SMAD4 depletion was associated with persistently higher levels of ROS and radiation-induced autophagy. Finally, SMAD4 depletion induced in vivo radioresistance in Panc-1-derived orthotopic tumor model (P = 0.038). More interestingly, we observed that the protein level of SMAD4 is inversely correlated with autophagy in orthotopic tumor tissue samples. Conclusions:Our results demonstrate that defective SMAD4 is responsible for radioresistance in pancreatic cancer through induction of ROS and increased level of radiation-induced autophagy.
https://ift.tt/2E6Py1V
Novel Metabolites Provide Insight to Health Benefits of Coffee
FRIDAY, March 30, 2018 -- Metabolomic profiling highlights potential mechanisms to explain coffee's health effects, according to a study published online March 15 in the Journal of Internal Medicine. Marilyn C. Cornelis, Ph.D., from Northwestern...
https://ift.tt/2GrZ0yz
Bariatric Surgery Lessens Knee OA Pain More in Certain Patients
FRIDAY, March 30, 2018 -- Laparoscopic gastric band (LAGB) surgery is associated with more improvement in knee osteoarthritis (OA) in younger patients and those without prior knee injury, according to a study published recently in Seminars in...
https://ift.tt/2GGMkrg
Receptivity to Tobacco Ads Linked to Progression to Use
FRIDAY, March 30, 2018 -- For adolescents, receptivity to tobacco advertising is associated with progression toward use, according to a study published online March 26 in JAMA Pediatrics. John P. Pierce, Ph.D., from the University of California, San...
https://ift.tt/2Gq8bzI
Simple Lung Function Tests in Primary Care Help ID Early COPD
FRIDAY, March 30, 2018 A peak flow meter or microspirometer can be used routinely in primary care among patients with suspected chronic obstructive pulmonary disease (COPD) for early case identification, according to a study published online March...
https://ift.tt/2GHFtgV
After Hockey Win, Fans' Heart Attack Risk Rises
FRIDAY, March 30, 2018 -- Following a professional hockey game victory, there is an increase in heart attack-related hospital admissions among male fans, according to a study published online March 29 in the Canadian Journal of Cardiology. Caroline...
https://ift.tt/2Gnor4q
Nanomedicine Approaches Against Parasitic Worm Infections
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2pSYofr
Shelf‐life enhancement of whole rainbow trout (Oncorhynchus mykiss) treated with Reshgak ice coverage
Food Science &Nutrition, EarlyView.
https://ift.tt/2pXfCaK
Transcytosis of payloads that are non-covalently complexed to bispecific antibodies across the hCMEC/D3 blood-brain barrier model
Journal Name: Biological Chemistry
Issue: Ahead of print
https://ift.tt/2uyv6r8
Functional characterization of the mouse Serpina1 paralog DOM-7
Journal Name: Biological Chemistry
Issue: Ahead of print
https://ift.tt/2GmROb9
O-1-35. The verification for stimulation characteristics of Cortical Stimulator
Bipolar stimulation (BS) used in intraoperative mapping is said to have less influence of leakage current. Its characteristics were actually verified while comparing with monopolar stimulation (MS).
https://ift.tt/2H0FA5i
S15-3. Why is theta burst stimulation effective?
As the first patterned protocol of repetitive transcranial magnetic stimulation (rTMS), theta burst stimulation (TBS) gives bursts containing 3 pulses at 50 Hz at 5 Hz in either an uninterrupted continuous train (continuous TBS, cTBS) or short trains with pauses in between (intermittent TBS, iTBS). TBS induces a cortical modulation effect outlasting the stimulation for up to an hour after 20–192 s of stimulation. Since TBS is usually given at a low intensity for a short period of time, coil overheat is rarely seen before the end of stimulation.
https://ift.tt/2E7OgDQ
O-1-25. Task-dependent modulation of cerebellar brain inhibition during motor imagery
The aim of study was to investigate cerebellar brain inhibition (CBI) is affected by imaginary muscle contraction (Contract-I) and relaxation (Relax-I) using paired pulse paradigm with transcranial magnetic stimulation (TMS) in healthy human. Participants performed tonic actual contraction and relaxation of right first dorsal interosseous (FDI) muscle with visual feedback using electromyography. The motor evoked potential (MEP) in right FDI induced by TMS over the left primary motor cortex with or without conditioning TMS over the right cerebellum was measured during no-imagery (No-I), Contract-I (1st experiment, n = 9) and Relax-I (2nd experiment, n = 20).
https://ift.tt/2GYWAsB
O-2-17. Influence of different types of orthoses on muscle synergy control during gait in stroke patients with hemiparesis
The purpose of this study was to verify the influence of lower limb orthoses on muscle synergy control during gait in stroke patients with hemiparesis. In four subjects with acute stroke, surface EMG signals from eight muscles of the paretic lower limb were measured during gait in two conditions (ankle foot orthosis; AFO or knee ankle foot orthosis; KAFO). The number of modules, muscle weightings and activation timing profile of each module were analyzed using non-negative matrix factorization. In two subjects (Fugl Meyer Assessment; FMA > 20) who walked with mild assistance, three modules were identified during gait with KAFO, whereas two modules were identified with AFO.
https://ift.tt/2GZMyay
O-2-24. Multimodal evoked potential study following posterior quadrantectomy in children with intractable epilepsy
To identify surgical effects on brainstem and cortical function objectively, we compared auditory brainstem response (ABR), somatosensory evoked potential (SEP) and flash visual evoked potential (fVEP) before and after posterior quadrantectomy (PQ) in 11 young children with intractable epilepsy associated with posterior quadrant cortical dysplasia. Mean age of seizure onset and the surgery was 1.4 months and 7.7 months old, respectively. Seven patients showed spasm and 2 had tonic seizures preoperatively.
https://ift.tt/2pVoZr9
O-1-24. Cortical silent period during force control task
We investigated whether transcranial magnetic stimulation (TMS)-induced cortical silent period (cSP), which reflects activation of the GABAergic inhibitory neural circuit in the primary motor cortex (M1), was modulated with dependency on actual output force and corticospinal excitability. Eleven healthy participants were asked to control the force of abduction of the right index finger to 10–100% of the maximum voluntary contraction. TMS was delivered to the left M1 during the task. The results showed that actual output force level, background electromyography activity (bEMG) and area of motor evoked potential (aMEP) in the right first dorsal interosseous muscle gradually increased with increasing target force level while cSP gradually decreased with increasing target force level.
https://ift.tt/2E7NZki
S19-4. Establishment of evidence-based physical therapy
Motor imagery and imitation have been widely used by physical therapist as part of rehabilitation program. However, there have been few evidences for the effect of these approaches on the physical therapy in terms of the neuroscience. Understanding of their neural mechanisms leads to establishment of evidence-based physical therapy (EBPT). Recently, we demonstrated some of the neural mechanism of motor imagery and imitation using MEG.
https://ift.tt/2H3mgEx
Transition Points for the Routine Integration of Palliative Care in Patients with Advanced Cancer
Increasing emphases are being placed upon early integration of palliative care for patients with advanced cancers, yet barriers to implementation in clinical practice remain. Criteria to standardise referral have been endorsed, but their application are yet to be tested at the population level.
https://ift.tt/2J7j9f3
Treatment of Anal Cancer Pain – A Case Report
Treatment of pain related to anal cancer remains challenging. A literature review shows very little data on how best to treat such pain. Opioids are frequently used to manage localized pain associated with anal cancer, but the efficacy of such treatment remains largely unknown. In addition, many expensive opioids and procedures tried in other studies and countries are lacking in less developed countries such as ours. We present that case of a young man diagnosed with stage III anal cancer and extreme sharp pain treated with suppositories containing a steroid and anesthetic resulting in significant improvement in his pain.
https://ift.tt/2E6RRlx
Cost-Effectiveness of Early Insertion of Transjugular Intrahepatic Portosystemic Shunts for Recurrent Ascites
Treatment options for recurrent ascites resulting from decompensated cirrhosis include serial large volume paracentesis and albumin infusion (LVP+A) or insertion of a transjugular intrahepatic portosystemic shunt (TIPS). Insertion of TIPSs with covered stents during early stages of ascites (early TIPS, defined as 2 LVPs within the past 3 weeks and less than 6 LVPs in the prior 3 months) significantly improves chances of survival and reduces complications of cirrhosis compared to LVP+A. However, it is not clear if TIPS insertion is cost-effective in these patients.
https://ift.tt/2GGo4Fz
Equivalent Efficacies of Reverse Hybrid and Bismuth Quadruple Therapies in Eradication of Helicobacter pylori Infection in a Randomized Controlled Trial
Bismuth quadruple therapy is recommended as a first-line treatment for Helicobacter pylori infection in the United States but hybrid therapy is an alternative option. Reverse hybrid therapy (proton pump inhibitor plus amoxicillin for 14 days, and clarithromycin plus metronidazole for the initial 7 days) is a simplified hybrid treatment. We aimed to assess the efficacies of reverse hybrid therapy vs bismuth quadruple therapy as first-line treatments for patients with H pylori infection in a randomized trial.
https://ift.tt/2Gq6pyH
Expression of C19MC miRNAs in HCC associates with stem-cell features and the cancer-testis genes signature
Intratumor heterogeneity of hepatocellular carcinoma (HCC) and, among HCC cell subsets, the cancer stem cell population (hCSC), is responsible for therapeutic resistance and disease relapse.
https://ift.tt/2pRrMli
Diagnostic Ability of Blue Laser Imaging Combined with Magnifying Endoscopy for Early Esophageal Cancer
Blue laser imaging (BLI) is a new image-enhanced endoscopy technique that utilizes a laser light source developed for narrow-band light observation.
https://ift.tt/2GWOZKQ
Cost-Effectiveness Analysis of Routine Magnetic Resonance Imaging in the Follow-Up of Patients with Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy
To estimate the clinical benefit and cost-effectiveness of routine head and neck magnetic resonance imaging (MRI) in the follow-up of patients with nasopharyngeal carcinoma (NPC) after definitive intensity-modulated radiotherapy (IMRT).
https://ift.tt/2GlrQot
Partial Laryngeal IMRT for T2N0 Glottic Cancer: Impact of Image Guidance and Radiotherapy Intensification
This single institution study shows a high local control for partial laryngeal IMRT in T2 glottic cancer over a transition from IGRT matching surrogate from initial bone to laryngeal soft tissue, and further enhancement without increasing late toxicity when biological effective dose (α/β=10 Gy) was increased from 66.7 to 72 Gy using 2.0 Gy/fraction instead of 2.4 Gy/fraction. The results underline the importance of appropriate IGRT strategies and radiotherapy intensification using partial laryngeal IMRT.
https://ift.tt/2IednqX
Daily Image-Guidance with Cone Beam Computed Tomography May Reduce Radiation Pneumonitis in Unresectable Non-Small Cell Lung Cancer
We found a decreased rate of Grade ≥ 2 radiation pneumonitis among inoperable non-small cell lung cancer patients receiving daily image-guided radiation therapy (IGRT) with cone-beam computed tomography (CBCT) after an initial 4-dimensional computed tomography simulation compared to daily IGRT with 2-dimensional orthogonal kilovoltage imaging. Future studies should consider the ability of CBCT to improve tumor localization and potentially reduce subacute pulmonary toxicity.
https://ift.tt/2Ijw1hb
Emerging MR Imaging Technologies for Radiation Therapy Planning and Response Assessment
Functional and molecular MRI techniques are capable of measuring biologic properties of tumor tissue. Knowledge of these biologic properties may improve radiation treatment by more accurately identifying tumor volumes, characterizing radioresistant subvolumes of tumor before radiation therapy (RT) and identifying recurrent disease following RT. Intravoxel incoherent motion (IVIM) MRI, blood oxygenation level dependent (BOLD) MRI, tissue oxygenation level dependent (TOLD) MRI, hyperpolarized 13C MRI, and chemical exchange saturation transfer (CEST) MRI are relatively new MRI techniques that have shown promise for contributing to RT planning and response assessment.
https://ift.tt/2GkyRpD
Mentorship experiences of early career academic radiation oncologists in North America
Given concerns about gender equity and career outcomes of academic radiation oncologists, we sought to gather evidence regarding mentorship experiences. We surveyed early career academic radiation oncologists within five years of board certification, using a pre-tested questionnaire. Our results suggest a need for increased facilitation of mentorship of all junior faculty through deliberate, structured programs, and further study is required to elucidate the mechanism driving gender imbalance in laboratory and translational research participation.
https://ift.tt/2GlgPDv
Study on the relationship between changes of immune cells and TNF-α in peripheral blood of patients with multidrug-resistant and extensively drug-resistant tuberculosis
OBJECTIVE: To investigate the relationship between changes in CD4- and CD8-positive immune cells and TNF-α in the peripheral blood of patients affected by multidrug-resistant and extensively drug-resistant tuberculosis.
PATIENTS AND METHODS: 179 patients suffering from tuberculosis treated in the Chest Hospital of Hebei from April 2010 to December 2015 were selected for the study. There were 47 cases affected by drug-resistant tuberculosis and 132 cases affected by non-drug-resistant tuberculosis. The control group included 183 healthy subjects examined during the same period. ELISA was used to compare and analyze serum levels of TNF-α, CD4- and CD8-positive cell levels, and CD4/CD8 ratio in the two groups.
RESULTS: CD4- and CD8-positive cell count, CD4/CD8 ratio, and serum TNF-a were significantly higher in patients with drug-resistant tuberculosis compared with healthy controls and the non-drug-resistant tuberculosis patients (p < 0.05). There was a positive correlation between TNF-α level and CD4/CD8 ratio (r=0.892, p < 0.05). Before treatment, the differences in the levels of TNF-a in the different groups of drug-resistant patients were insignificant (p >0.05). After treatment, the levels of TNF-a in the different groups of drug-resistant patients were decreased, except for patients with extensively drug-resistant tuberculosis, whose levels were significantly decreased compared with before treatment (t = 0.648, p>0.05). The differences in the levels of TNF-α in the other groups of patients before and after treatment were statistically significant (t = 8.497, 6.258, 5.346, p < 0.05, fully sensitive tuberculosis single drug-resistant tuberculosis, multidrug-resistant tuberculosis, respectively).
CONCLUSIONS: The level of TNF-α plays a critical role in the evaluation of the severity of patients with drug-resistant tuberculosis and it has a clinical value.
L'articolo Study on the relationship between changes of immune cells and TNF-α in peripheral blood of patients with multidrug-resistant and extensively drug-resistant tuberculosis sembra essere il primo su European Review.
https://ift.tt/2GZB9aH
Fibrosis‐4 index predicts cirrhosis risk and liver‐related mortality in 2075 patients with chronic HBV infection
Alimentary Pharmacology &Therapeutics, EarlyView.
https://ift.tt/2GGoJXI
Review article: nonclinical and clinical pharmacology, pharmacokinetics and pharmacodynamics of etrolizumab, an anti‐β7 integrin therapy for inflammatory bowel disease
Alimentary Pharmacology &Therapeutics, EarlyView.
https://ift.tt/2GrRfso
Neuron-Macrophage Co-cultures to Activate Macrophages Secreting Molecular Factors with Neurite Outgrowth Activity
The current protocol presents experimental procedures to stimulate cultured macrophages to be endowed with capacity to release molecular factors that promote neurite outgrowth. Treatment of cAMP to the neuron-macrophage co-cultures induces the macrophages to produce conditioned medium that possesses strong neurite outgrowth activity.
https://ift.tt/2uApfS4
Survival benefit of lymph node dissection in surgery for colon cancer in elderly patients: A multicenter propensity score‐matched study in Japan
Asian Journal of Endoscopic Surgery, EarlyView.
https://ift.tt/2Iji2aT
Study of candidate gene cHRNA4 for familial epilepsy syndrome
OBJECTIVE: To screen a three-generation familial partial epilepsy with variable foci (FPEVF) family with epilepsy to identify the cHRNA4 gene (a candidate gene).
PATIENTS AND METHODS: A total of 18 members of the three-generation FPEVF family with partial epilepsy were selected, and 18 blood samples were collected for investigation. Among them, five members were affected by epilepsy, and another 13 members were not affected. A pedigree chart was mapped to comprehensively analyze the clinical characteristics of each member, including ictal semiology, electroencephalogram (EEG), past medical history, MRI features, neuropsychological MMSE (mini-mental state examination) scores, etc. PCR and Sanger sequencing method were used to screen the mutant gene cHRNA4.
RESULTS: cHRNA4 genes of all affected members were positively mutated, and that of the unaffected members were negative. The positive mutation was base A instead of base G.
CONCLUSIONS: cHRNA4 is the causative gene of FPEVF, and genes of the affected members are all heterozygotes mutations.
L'articolo Study of candidate gene cHRNA4 for familial epilepsy syndrome sembra essere il primo su European Review.
https://ift.tt/2GmQcOR
Effects of sevoflurane post-conditioning in cerebral ischemia-reperfusion injury via TLR4/NF-κB pathway in rats
OBJECTIVE: The aim of the study was to investigate the anti-inflammatory effect of sevoflurane post-conditioning on cerebral ischemia-reperfusion injury in rats.
MATERIALS AND METHODS: Thirty Sprague Dawley (SD) rats were randomly divided into 3 groups: sham operation group (Sham), ischemia/reperfusion injury (I/R) group and sevoflurane post-conditioning group (Se). Hematoxylin-eosin (HE) staining was used to observe the inflammatory response in the brain tissue. The levels of TNF-α, IL-1β, IL-6 in serum were measured by ELISA. The mRNA and protein expression of TLR4 and NF-κB p65 were detected by RT-PCR and Western blot in the brain tissue.
RESULTS: The post-conditioning of sevoflurane decreased the level of inflammatory reaction in ischemic-reperfusion rat cerebral infarction area and reduced the levels of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6 in rats with ischemia-reperfusion injury. In addition, after treatment with sevoflurane, the mRNA and protein expression of TLR4 and NF-κBp65 in TLR4/NF-κB pathway was inhibited.
CONCLUSIONS: Sevoflurane post-conditioning can decrease the inflammatory reaction in cerebral infarct area induced by cerebral ischemia-reperfusion injury in rats. The neuroprotective effect mechanism of sevoflurane may be related to TLR4/NF-κB signaling pathway.
L'articolo Effects of sevoflurane post-conditioning in cerebral ischemia-reperfusion injury via TLR4/NF-κB pathway in rats sembra essere il primo su European Review.
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miR-424 protects PC-12 cells from OGD-induced injury by negatively regulating MKP-1
OBJECTIVE: It's of great significance to investigate the novel targets of drugs for the treatment of stroke. In this study, we explored the neuroprotective role of miR-424 in oxygen glucose deprivation (OGD)-induced injuries in PC-12 cells.
MATERIALS AND METHODS: PC-12 cells were subjected to OGD stimulation to mimic ischemic injury. The expressions of miR-424 and mitogen-activated protein kinase phosphatase-1 (MKP-1) were altered by transient transfection with miR-424 mimic, miR-424 inhibitor, pEX-MKP-1, or sh-MKP-1. Cell counting kit-8 (CCK-8) assay, flow cytometry, and quantitative reverse transcription polymerase chain reaction (qRT-PCR), were conducted to respectively detect cell viability, apoptotic cells, and the expression of miR-424 and MKP-1. The protein expressions of several factors were determined by Western blot. Meanwhile, relative luciferase activity assay was done to verify the predicted targets association.
RESULTS: OGD induced injury in PC-12 cells by suppressing cell viability and inducing apoptosis. OGD also induced the expression of miR-424 in PC-12 cells. Overexpression of miR-424 protected PC-12 cells from OGD-induced injury by increasing cell viability and decreasing apoptosis. MKP-1 was a direct target of miR-424, and its expression was negatively regulated by miR-424. Up-regulation of expression of MKP-1 aggravated OGD-induced cell injury by inhibiting the expression of hypoxia-inducible factor 1α (HIF-1α), thus inhibiting the PI3K/AKT/mTOR pathways.
CONCLUSIONS: miR-424 protected PC-12 cells from OGD-induced injury through direct suppression of MKP-1 expression, as MKP-1 promoted OGD-induced cell injury by inhibiting the expression of HIF-1α and PI3K/AKT/mTOR pathways.
L'articolo miR-424 protects PC-12 cells from OGD-induced injury by negatively regulating MKP-1 sembra essere il primo su European Review.
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Changes in cerebrovascular reactivity in healthy adults after acute exposure to high altitude
OBJECTIVE: To study changes in the cerebrovascular reactivity (CVR) at different altitude area in healthy adults.
SUBJECTS AND METHODS: CVR was tested using transcranial Doppler combined with CO2 inhalation, near-infrared spectroscopy (NIRS) was used to detect the regional cerebral oxygen saturation (rScO2). Blood samples were collected, and the vasoactive substances in serum were detected using the enzyme-linked immunosorbent assay. In this study, 59 healthy adults were divided into 3 groups: low altitude group, medium altitude group and high altitude group. All the indicators in low altitude group were tested at 24h before departure and after arrival from Beijing (at an altitude of 44.4 m) to Xining (at a medium altitude of 2200 m). Then, after resting for 48h, all the indicators were tested at 24h and 48h after arrival from Xining (at a medium altitude of 2200 m) to Yushu Jiegu town (at a high altitude of 3700 m) together with those at the medium altitude. Intergroup comparisons were made for the subjects in the three altitudes.
RESULTS: There was an increase in the CVR in low altitude group after acute exposure to high altitude, and the difference was significant (CVR: 1.94re was vs. 0.91±0.53, p<0.001); the CVR index was increased, and the difference was significant [cerebrovascular reserve index (CVRI): 3.65he CVR vs. 1.37e CVR, p<0.001]; the rScO2 level was decreased with the increase of altitude, and the difference was significant [(66.78±4.61)% vs. (70.29±4.52)%, p<0.001]. The levels of vasoactive substances in low altitude group were decreased after acute exposure to high altitude compared with those before exposure: NO: [(79.14±9.54) μmol/L vs. (58.01±9.93) μmol/L, p<0.001]; serum eNOS level was increased, and the difference was significant [(77.23±6.20) pg/ml vs. (65.07±9.82) pg/ml, p<0.001]; EPO: [(84.68±13.16) pg/ml vs. (65.01±5.92) pg/ml, p<0.001]; VEGF: [(71.91±11.62) pg/ml vs. (54.92±11.86) pg/ml, p<0.001]; sFlt: [(384.18±42.73) pg/ml vs. (320.62±78.96) pg/ml, p<0.001].
There was also an increase in CVR in medium altitude group after acute exposure to high altitude, and the difference was significant [CVR: 2.00±0.79 vs. 0.91±0.66, p<0.001]; the difference of CVRI was significant [3.83±0.67 vs. 1.67±0.87, p<0.001]; rScO2 was slightly decreased with the increase of altitude, and the difference was not statistically significant [(67.53±4.61) % vs. (69.63±5.59) %, p<0.001]. Before exposure to high altitude area, the levels of NO, NOS, EPO, VEGF, and sFlt in low and medium altitude groups were higher than those in high altitude group. CVR level of subjects at different altitudes was negatively related to the ScO2 (r=-0.91) but positively related to NO and NOS levels (rs=0.89, r=0.75); CVR was moderately related to VEGF and EPO (rs=0.45, r=0.42). rScO2 was positively related to RBC, HB and VEGF levels (r=0.89, r=0.75, rs=0.86), but had a moderately negative correlation with NO and NOS levels (rs=-0.52, r=-0.57).
CONCLUSIONS: After subjects at a low altitude are exposed to high altitude rapidly, CVR is increased, RBC and vasoactive substances in serum, such as NO, eNOS, and EPO, are dramatically increased, VEGF is increased first and then decreased, sFlt-1 level is increased gradually, and rScO2 level is gradually decreased with the increase of altitude, indicating the local brain anoxia of subjects at a high altitude.
L'articolo Changes in cerebrovascular reactivity in healthy adults after acute exposure to high altitude sembra essere il primo su European Review.
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Endothelial progenitor cell miR-126 promotes homing of endothelial progenitor cells within arterial thrombus in patients with cerebral infarction and its molecular mechanism
OBJECTIVE: The present study was designed to investigate the effect of microRNA-126 (miR-126) on the migration and homing of endothelial progenitor cells (EPCs) within arterial thrombus of cerebral infarction patients.
MATERIALS AND METHODS: EPCs from rat bone marrow were isolated, and miR-126 overexpressed EPCs were constructed by lentiviral transfection. Then, the middle cerebral artery occlusion (MCAO) model was established by the method of thread ligation. Successfully established model rats were randomly divided into miR-126 overexpression EPC group, miR-126 wild type EPC group, and normal saline group. One day after the infarction, the miR-126 overexpression EPCs, miR-126 wild type EPCs, and normal saline, were injected into the lateral ventricle of the corresponding groups. Also, the transplanted cells were tracked by cell dye SPDiIC18. The expression of tight junction proteins ZO-1 and Claudin-5 in brain tissue was detected by Western blotting.
RESULTS: Transplanted cells were detected in the cerebral infarction area 3 days after transplantation by cell dye SP-DiIC18. The number of homing EPCs in miR-126 overexpression group was significantly higher than that of miR-126 wild type EPC group (p < 0.05). Also, the protein expression of ZO-1 and Claudin-5 in the miR- 126 overexpression EPC group was significantly higher compared with that of the miR-126 wild type EPC group and the normal saline group.
CONCLUSIONS: miR-126 overexpression EPCs, which were transplanted in the lateral ventricle, can home to the cerebral infarction areas via increasing increase
L'articolo Endothelial progenitor cell miR-126 promotes homing of endothelial progenitor cells within arterial thrombus in patients with cerebral infarction and its molecular mechanism sembra essere il primo su European Review.
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The role of AMPK/mTOR signal pathway in brain injury following chronic intermittent hypoxia in growing rats
OBJECTIVE: To investigate the role of AMPK-mTOR signal pathway in brain injury induced by chronic intermittent hypoxia (CIH) in young rats.
MATERIALS AND METHODS: Forty healthy male Sprague-Dawley rats (3-4 weeks old, weighing 80-100 g) were randomly assigned to four groups: 2-week-CIH group (2IH), 4-week-CIH group (4IH), 2-week-simulated air control group (2AC) and 4-week-simulated air control group (4AC). TUNEL staining was used to detect the cell apoptosis in the hippocampus and pre-frontal cortexes, respectively. The Western blot was conducted to analysis the P-AMPK (Phospho-AMP-activated protein kinase) and P-mTOR (phosphorylated mammalian target of rapamycin) protein expression.
RESULTS: The neurons apoptosis in the hippocampus and pre-frontal cortex in 2IH and 4IH groups increased significantly, compared with that of in 2AC and 4AC groups, (p<0.05, respectively). Moreover, 4IH group exhibited significantly increased apoptosis rates than 2IH group (p<0.05). 2IH and 4IH groups exhibited increased protein expression levels of P-AMPK in the hippocampus and prefrontal cortexes compared with 2AC and 4AC groups (p<0.05, respectively), whereas the protein expression of P-mTOR decreased after CIH treatment (p<0.05, respectively). Higher expression levels of P-AMPK and lower levels of P-mTOR were observed in 4IH group compared to 2IH group. No difference of apoptotic cells and protein expression of P-AMPK and P-mTOR was exhibited between 2AC and 4AC groups.
CONCLUSIONS: CIH induces neural apoptosis in a time-dependent manner by activating AMPK and inhibiting mTOR phosphorylation in young rats.
L'articolo The role of AMPK/mTOR signal pathway in brain injury following chronic intermittent hypoxia in growing rats sembra essere il primo su European Review.
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Trps1 is associated with the multidrug resistance of lung cancer cell by regulating MGMT gene expression
Cancer Medicine, EarlyView.
https://ift.tt/2pRhhiE
Effect of ulixertinib, a novel ERK1/2 inhibitor, on the QT/QTc interval in patients with advanced solid tumor malignancies
Abstract
Purpose
The aim of this analysis was to investigate the potential for ulixertinib (BVD-523) to prolong cardiac repolarization. The mean prolongation of the corrected QT (QTc) interval was predicted at the mean maximum drug concentrations of the recommended phase 2 dose (RP2D; 600 mg BID) and of higher concentrations. In addition, the effect of ulixertinib on other quantitative ECG parameters was assessed.
Methods
In a two-part, phase 1, open-label study in adults with advanced solid tumors, 105 patients [24 in Part 1 (dose escalation) and 81 in Part 2 (cohort expansion)] were included in a QT prolongation analysis. Electrocardiograms (ECGs) extracted from 12-lead Holter monitors, along with time-matched pharmacokinetic blood samples, were collected over 12 h on cycle 1 day 1 and cycle 1 day 15 and analyzed by a core ECG laboratory.
Results
A small increase in heart rate was observed on both study days (up to 5.6 bpm on day 1 and up to 7 bpm on day 15). The estimated mean changes from baseline in the study-specific QTc interval (QTcSS), at the ulixertinib Cmax, were − 0.529 ms (90% CI − 6.621, 5.562) on day 1 and − 9.202 ms (90% CI − 22.505, 4.101) on day 15. The concentration: QTc regression slopes were mildly positive but not statistically significant [0.53 (90% CI − 1.343, 2.412) and 1.16 (90% CI − 1.732, 4.042) ms per µg/mL for days 1 and 15, respectively]. Ulixertinib had no meaningful effect on PR or QRS intervals.
Conclusions
Ulixertinib administered to patients with solid tumors at clinically relevant doses has a low risk for QT/QTc prolongation or any other effects on ECG parameters.
Registration
The study is registered at Clinicaltrials.gov (NCT01781429) and was sponsored by BioMed Valley Discoveries.
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Evaluation of Stem Cell Therapies in a Bilateral Patellar Tendon Injury Model in Rats
https://ift.tt/2J5hnLw
Lower Energy Consumption for South Asian Migrants With T2DM
FRIDAY, March 30, 2018 -- Among South Asian (SA) migrants in the United States, those with type 2 diabetes mellitus (T2DM) consume less total energy and have lower consumption of many nutrients than those without T2DM, according to a study published...
https://ift.tt/2uzaWNt
Early Age-Related Macular Degeneration Linked to High HDL
FRIDAY, March 30, 2018 -- There is a higher risk for early age-related macular degeneration (AMD) in individuals with high plasma high-density lipoprotein cholesterol levels, according to a study published online March 29 in JAMA...
https://ift.tt/2Gp0uxO
Aortic Valve Replacement in Elderly Tied to High Mortality
FRIDAY, March 30, 2018 -- The 10-year mortality rate in elderly patients who receive surgical aortic valve replacement (SAVR) is considerable, according to a study published in the April 3 issue of the Journal of the American College of...
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ACA Has Provided Better Access to Care for Cancer Survivors
FRIDAY, March 30, 2018 -- Cancer survivors are more likely to have difficulty accessing and affording health care, but the proportion reporting these issues is decreasing, according to a study published online March 29 in JAMA Oncology. Ryan D....
https://ift.tt/2uB4wO4
Montreal Parkinson Risk of Dementia Scale Deemed Accurate
FRIDAY, March 30, 2018 -- The office-based, eight-item Montreal Parkinson Risk of Dementia Scale is a valid predictor of development of dementia, according to a study published online March 26 in JAMA Neurology. Benjamin K. Dawson, from McGill...
https://ift.tt/2GlJMiX
Lag in Progress Against Lung CA Mortality in Midwest, Appalachia
FRIDAY, March 30, 2018 -- In the Midwest and Appalachia there are areas where progress against lung cancer mortality among women is lagging compared with the rest of the nation, according to a study published March 30 in Cancer Epidemiology,...
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3, 6 Month Adjuvant CAPOX Equally Effective for Colon Cancer
THURSDAY, March 29, 2018 -- For patients with stage III colon cancer, three months of capecitabine and oxaliplatin (CAPOX) therapy is not noninferior to six months of therapy overall, according to a study published in the March 20 issue the New...
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Pectoralis Major Tears Described in Deployed Military Personnel
FRIDAY, March 30, 2018 -- Deployed military personnel may be at high risk for pectoralis major tears, according to a study published online in the Journal of Orthopedics & Rheumatology. Dane Salazar, M.D., from the Saint Louis University School...
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Rate of MI, Stroke Higher After Respiratory Infection
FRIDAY, March 30, 2018 -- The risk for myocardial infarction (MI) or stroke remains higher after laboratory-confirmed Streptococcus pneumoniae or influenza, according to a study published March 21 in the European Respiratory Journal. Charlotte...
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Childhood Irritability, Depressive Mood Linked to Suicidality Later
FRIDAY, March 30, 2018 -- Children with high irritability and depressive/anxious mood have increased suicidality risk during adolescence, according to a study published online March 28 in JAMA Psychiatry. Massimiliano Orri, Ph.D., from the Institut...
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Hearing What You See
A recent gif image has been circulating where individual can report hearing a "thud" sound
https://ift.tt/2GmIFzt
Development of a new patient-derived xenograft humanised mouse model to study human-specific tumour microenvironment and immunotherapy
Objective
As the current therapeutic strategies for human hepatocellular carcinoma (HCC) have been proven to have limited effectiveness, immunotherapy becomes a compelling way to tackle the disease. We aim to provide humanised mouse (humice) models for the understanding of the interaction between human cancer and immune system, particularly for human-specific drug testing.
DesignPatient-derived xenograft tumours are established with type I human leucocyte antigen matched human immune system in NOD-scid Il2rg–/– (NSG) mice. The longitudinal changes of the tumour and immune responses as well as the efficacy of immune checkpoint inhibitors are investigated.
ResultsSimilar to the clinical outcomes, the human immune system in our model is educated by the tumour and exhibits exhaustion phenotypes such as a significant declination of leucocyte numbers, upregulation of exhaustion markers and decreased the production of human proinflammatory cytokines. Notably, cytotoxic immune cells decreased more rapidly compared with other cell types. Tumour infiltrated T cells have much higher expression of exhaustion markers and lower cytokine production compared with peripheral T cells. In addition, tumour-associated macrophages and myeloid-derived suppressor cells are found to be highly enriched in the tumour microenvironment. Interestingly, the tumour also changes gene expression profiles in response to immune responses by upregulating immune checkpoint ligands. Most importantly, in contrast to the NSG model, our model demonstrates both therapeutic and side effects of immune checkpoint inhibitors pembrolizumab and ipilimumab.
ConclusionsOur work provides a model for immune-oncology study and a useful parallel-to-human platform for anti-HCC drug testing, especially immunotherapy.
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Effect of cultivation mode on the production of docosahexaenoic acid by Tisochrysis lutea
In this study, Tisochrysis lutea was cultivated in mixotrophic and heterotrophic cultures with glycerol as a carbon source and with glucose and acetate for comparison; autotrophic cultivation was the control grou...
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Cancers, Vol. 10, Pages 99: Treatment Options for Paediatric Anaplastic Large Cell Lymphoma (ALCL): Current Standard and beyond
Cancers, Vol. 10, Pages 99: Treatment Options for Paediatric Anaplastic Large Cell Lymphoma (ALCL): Current Standard and beyond
Cancers doi: 10.3390/cancers10040099
Authors: Nina Prokoph Hugo Larose Megan Lim G. Burke Suzanne Turner
Anaplastic Lymphoma Kinase (ALK)-positive Anaplastic Large Cell Lymphoma (ALCL), remains one of the most curable cancers in the paediatric setting; multi-agent chemotherapy cures approximately 65–90% of patients. Over the last two decades, major efforts have focused on improving the survival rate by intensification of combination chemotherapy regimens and employing stem cell transplantation for chemotherapy-resistant patients. More recently, several new and 'renewed' agents have offered the opportunity for a change in the paradigm for the management of both chemo-sensitive and chemo-resistant forms of ALCL. The development of ALK inhibitors following the identification of the EML4-ALK fusion gene in Non-Small Cell Lung Cancer (NSCLC) has opened new possibilities for ALK-positive ALCL. The uniform expression of CD30 on the cell surface of ALCL has given the opportunity for anti-CD30 antibody therapy. The re-evaluation of vinblastine, which has shown remarkable activity as a single agent even in the face of relapsed disease, has led to the consideration of a revised approach to frontline therapy. The advent of immune therapies such as checkpoint inhibition has provided another option for the treatment of ALCL. In fact, the number of potential new agents now presents a real challenge to the clinical community that must prioritise those thought to offer the most promise for the future. In this review, we will focus on the current status of paediatric ALCL therapy, explore how new and 'renewed' agents are re-shaping the therapeutic landscape for ALCL, and identify the strategies being employed in the next generation of clinical trials.
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Measuring Gene Expression in Bombarded Barley Aleurone Layers with Increased Throughput
An improved protocol is presented for the measurement of transient gene expression from reporter constructs in barley aleurone cells after particle bombardment. The combination of automated grain grinding with 96-well plate enzyme assays provides high throughput for the procedure.
https://ift.tt/2GLl3DM
An Efficient and Simple Method to Establish NK and T Cell Lines from Patients with Chronic Active Epstein-Barr Virus Infection
A simple method for obtaining NK and T cell clones from CAEBV patients was developed with high efficiency, a small amount of peripheral blood, and a low-dose of IL-2.
https://ift.tt/2IdAXEb
The significance of interfamilial relationships on birth preparedness and complication readiness in Pakistan
Publication date: Available online 30 March 2018
Source:Women and Birth
Author(s): Usman Ghani, Susan Crowther, Yasir Kamal, Muhammad Wahab
BackgroundIn the interests of improving maternal health care and survival, the issue of birth preparedness and complication readiness has been much debated and has remained a priority for the international health community. The provision of birth preparedness and complications readiness is determined by a range of different factors.AimThe main aim of this study is to identify and measure the influence of husbands and other family relationships on birth preparedness and complications readiness in the Khyber Pakhtunkhwa province of Pakistan.MethodsThis study is a cross-sectional exploratory study. Data was collected through a survey questionnaire. Logistic regression and descriptive analysis was used.FindingsAnalysis indicated that the mother-in-law's role, men's and women's level of education and interfamilial relationships are still the most significant factors influencing birth preparedness and complications readiness. Of the respondents, 86% were receiving antenatal care and 76.5% were planning for the birth to take place in state-run hospitals or private obstetric and gynae clinics.ConclusionThe tendency to take up antenatal care in Khyber Pakhtunkhwa can mainly be credited to a mutual understanding between husband and wife and a good relationship between the woman and her mother-in-law. Highlighting the significance of these relationships has implications for ensuring birth preparedness and complications readiness.
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Intramuscular islet allotransplantation in type 1 diabetes mellitus
OBJECTIVE: Alternative sites to the liver for islet transplantation have been studied for a long time. Intramuscular islet transplantation appears to be an alternative site to the liver because of the ease of access. First islet autotransplantations were reported in patients after total pancreatectomies. The transplanted islets showed a proper revascularization and their function was observed for up to 2 years after the implant. However, only a few cases of autotransplantation and no allotransplantation have been performed. The aim of this study was to verify the feasibility of islet allotransplantation into muscles.
PATIENTS AND METHODS: In four patients affected by type 1 diabetes mellitus in which liver islet allotransplantation was contraindicated, human islets were transplanted into patients' arm muscle with local anesthesia.
RESULTS: The surgery was minimally invasive, without complications. In one patient a moderate local inflammatory reaction was observed at the site of the implant, which resolved spontaneously within 4 days. Islet graft function was observed after transplantation in all patients, but it progressively disappeared in 3 out 4 patients within a short time.
CONCLUSIONS: In this first ever-reported intramuscular pancreatic islet allotransplantation, the procedure appears feasible but new strategies must be envisaged to significantly improve islet engraftment and the long-term graft function.
L'articolo Intramuscular islet allotransplantation in type 1 diabetes mellitus sembra essere il primo su European Review.
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Analysis of the correlation between non-alcoholic fatty liver disease and bone metabolism indicators in healthy middle-aged men
OBJECTIVE: To investigate the relationship between bone metabolic indicators and non-alcoholic fatty liver disease (NAFLD) in healthy middle-aged men.
PATIENTS AND METHODS: The bone metabolic indicators of 232 healthy middle-age men with NAFLD (NAFLD group) and 308 healthy controls without fatty liver (Control group) were measured, including non-collagenous osteocalcin, the procollagen type 1 N-terminal propeptide (P1NP), beta-C-terminal telopeptide of type I collagen (β-CTX). The Student's t-test was used to analyze the differences in the bone metabolic indicators, age, clinical data, biochemical indicators, and the indicators of glucose and lipid metabolism between the two groups. The correlation of fatty liver-related indicators was detected using the logistic regression analysis.
RESULTS: The body mass index (BMI), diastolic blood pressure, and heart rate in NAFLD group were significantly higher than those in Control group. Among the indicators of glucose and lipid metabolism in NAFLD group, the levels of blood glucose [fasting plasma glucose, postprandial blood glucose and hemoglobin A1c (HbA1c)] were significantly higher than those in Control group. In addition, the insulin resistance and secretion indexes were also significantly higher than those in Control group. The levels of lipid metabolic indicators such as triglyceride were higher, but high-density lipoprotein cholesterol was lower than that in Control group. From logistic regression analysis, the BMI, Homeostasis model assessment (HOMA)-β, HOMA-IR, HbA1c and P1NP were positively associated with the occurrence of NAFLD.
CONCLUSIONS: The bone metabolic indicator P1NP might be a potential predicator for the diagnosis of NAFLD in clinical application.
L'articolo Analysis of the correlation between non-alcoholic fatty liver disease and bone metabolism indicators in healthy middle-aged men sembra essere il primo su European Review.
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Islet transplantation 30 years after the first transplants
First clinical islet allotransplantation in patients affected by type 1 diabetes mellitus was performed about 30 years ago. Despite the progressive improvement of the success rate, the clinical indication to the islet allotransplantation remains limited to selected patients affected by brittle type 1 diabetes mellitus. The burden of the immunosuppression therapy still represents the main critical issue but other areas might be subject to further improvements, such as the islet production, islet engraftment and long-term function. Several strategies have been proposed to increase the success rate of pancreas digestion and islet purification or to facilitate islet engraftment by reducing islet hypoxia and the inflammatory reaction occurring in the site of transplantation. The co-transplantation of progenitors of beta cell together with the islets has expected to contribute to prolong graft function. Clinical trials are expected soon. Scientific advances, as well as economical efforts, are required to make this procedure a real therapeutical option for patients with type 1 diabetes mellitus.
L'articolo Islet transplantation 30 years after the first transplants sembra essere il primo su European Review.
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The role of adiponectin gene mediated by NF-κB signaling pathway in the pathogenesis of type 2 diabetes
OBJECTIVE: To investigate the role of adiponectin (ADPN) gene mediated by NF-κB signaling pathway in the pathogenesis of type 2 diabetes (T2DM).
PATIENTS AND METHODS: The levels of expression of ADPN were measured by fluorescence quantitative PCR technology, enzyme-linked immunosorbent assay, Western-blotting and immunohistochemistry in 78 patients with type 2 diabetes.
RESULTS: Compared with the normal population, the levels of expression of ADPN and NF-κB mRNA in the blood of patients with type 2 diabetes were significantly reduced (p < 0.05). The detection of ADPN gene protein expression in normal population and patients with type 2 diabetes by enzyme-linked immunosorbent assay showed that ADPN gene protein expression in type 2 diabetic patients (1.26 ± 0.73) µg/l was significantly lower (p < 0.05) than ADPN gene protein expression of the normal population (3.26 ± 1.25) µg/l. At the same time, the detection of the expression of NF-κB gene showed that the protein expression in type 2 diabetic patients (0.58 ± 0.15) µg/l was significantly lower (p < 0.05) than that in the normal population (1.67 ± 1.04) µg/l. The results of Western-blotting were consistent with the results of enzyme-linked immunosorbent assay. Immunohistochemical results also showed that the percentage of ADPN positive cells in patients with type 2 diabetes (25.47%) was significantly lower (p < 0.05) than that in the normal population (79.47%).
CONCLUSIONS: ADPN gene in the human body can be involved in the pathogenesis of T2DM through the NF-κB signaling pathway.
L'articolo The role of adiponectin gene mediated by NF-κB signaling pathway in the pathogenesis of type 2 diabetes sembra essere il primo su European Review.
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Impact of formulation on the iontophoretic delivery of the FOLFIRINOX regimen for the treatment of pancreatic cancer
Abstract
Purpose
Effective treatment of patients with locally advanced pancreatic cancer is a significant unmet clinical need. One major hurdle that exists is inadequate drug delivery due to the desmoplastic stroma and poor vascularization that is characteristic of pancreatic cancer. The local iontophoretic delivery of chemotherapies provides a novel way of improving treatment. With the growing practice of highly toxic combination therapies in the treatment of pancreatic cancer, the use of iontophoresis for local delivery can potentiate the anti-cancer effects of these therapies while sparing unwanted toxicity. The objective of this study was to investigate the impact of formulation on the electro-transport of the FOLFIRINOX regimen for the development of a new treatment for pancreatic cancer.
Methods
Three formulations of the FOLFIRINOX regimen (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) were generated at a fixed pH of 6.0 and were referred to as formulation A (single drug solution with all four drugs combined), formulation B (two drug solutions with two drugs per solution), and formulation C (four individual drug solutions). Anodic iontophoresis of the three different formulations was evaluated in orthotopic patient-derived xenografts of pancreatic cancer.
Results
Iontophoretic transport of the FOLFIRINOX drugs was characterized according to organ exposure after a single device treatment in vivo. We report that the co-iontophoresis of two drug solutions, leucovorin + oxaliplatin and 5-fluorouracil + irinotecan, resulted in the highest levels of cytotoxic drugs in the tumor compared to drugs delivered individually or combined into one solution. There was no significant difference in plasma, pancreas, kidney, and liver exposure to the cytotoxic drugs delivered by the three different formulations. In addition, we found that reducing the duration of iontophoretic treatment from 10 to 5 min per solution resulted in a significant decrease in drug concentrations.
Conclusions
Underlying the difference in drug transport of the formulations was electrolyte concentrations, which includes both active and inactive components. Electrolyte concentrations can hinder or improve drug electro-transport. Overall, balancing electrolyte concentration is needed for optimal electro-transport.
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Cardiopulmonary fitness before and after neoadjuvant chemotherapy in patients with oesophagogastric cancer
British Journal of Surgery, EarlyView.
https://ift.tt/2GXhs3j
Construct and criterion validity testing of the Non‐Technical Skills for Surgeons (NOTSS) behaviour assessment tool using videos of simulated operations
British Journal of Surgery, EarlyView.
https://ift.tt/2uCpMmy
Outcome of open abdominal management following military trauma
British Journal of Surgery, EarlyView.
https://ift.tt/2GZIpn9
Relationship between intraoperative non‐technical performance and technical events in bariatric surgery
British Journal of Surgery, EarlyView.
https://ift.tt/2uCpM62
Translating Research into Health Policy: Stock Albuterol Legislation
https://ift.tt/2uAOofm
Association of High-Dose Ibuprofen Use, Lung Function Decline, and Long-Term Survival in Children with Cystic Fibrosis
Annals of the American Thoracic Society, Volume 15, Issue 4, Page 485-493, April 2018.
https://ift.tt/2GXcCDb
A Practical Approach to Severe Asthma in Children
Annals of the American Thoracic Society, Volume 15, Issue 4, Page 399-408, April 2018.
https://ift.tt/2E7UnaW
Evaluation of Practice Changes in the Care of Patients with Septic Shock during the U.S. Norepinephrine Shortage
Annals of the American Thoracic Society, Volume 15, Issue 4, Page 509-511, April 2018.
https://ift.tt/2GWPnsO
Variation in Cilia Protein Genes and Progression of Lung Disease in Cystic Fibrosis
Annals of the American Thoracic Society, Volume 15, Issue 4, Page 440-448, April 2018.
https://ift.tt/2E7Kg5X
The Road to Precision Medicine in Chronic Obstructive Pulmonary Disease: Squeezing More Out of Chest Computed Tomography Scans
https://ift.tt/2GYERRM
Epidemiology of Hypersensitivity Pneumonitis among an Insured Population in the United States: A Claims-based Cohort Analysis
Annals of the American Thoracic Society, Volume 15, Issue 4, Page 460-469, April 2018.
https://ift.tt/2uAOnbi
Chronic Obstructive Pulmonary Disease Postexacerbation: Let’s Get Physical?
https://ift.tt/2GXie0i
Reply: Further Need for Evidence in Long-Term Oxygen Therapy
Annals of the American Thoracic Society, Volume 15, Issue 4, Page 512-513, April 2018.
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Ambient Pollution Contributes Not Only to Pneumonia Cases but Also to Disease Severity
https://ift.tt/2GV5Ttj
A Bone to Pick with a Lung Disease
https://ift.tt/2uDljAe
Mass Incarceration and Pulmonary Health: Guidance for Clinicians
https://ift.tt/2GWPbtA
Home-based Physical Activity Coaching, Physical Activity, and Health Care Utilization in Chronic Obstructive Pulmonary Disease. Chronic Obstructive Pulmonary Disease Self-Management Activation Research Trial Secondary Outcomes
Annals of the American Thoracic Society, Volume 15, Issue 4, Page 470-478, April 2018.
https://ift.tt/2E6WSKP
Further Need for Evidence in Long-Term Oxygen Therapy
https://ift.tt/2GZDjHx
Getting to the Root of the Matter
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The Long and the Short of It in Cystic Fibrosis Clinical Research Outcomes
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Powers and Pitfalls of Using Administrative Data to Study the Epidemiology of Interstitial Lung Diseases
https://ift.tt/2E78vl4
Short-Term Air Pollution and Incident Pneumonia. A Case–Crossover Study
Annals of the American Thoracic Society, Volume 15, Issue 4, Page 449-459, April 2018.
https://ift.tt/2GXidtg
Domiciliary High-Flow Nasal Cannula Oxygen Therapy for Patients with Stable Hypercapnic Chronic Obstructive Pulmonary Disease. A Multicenter Randomized Crossover Trial
Annals of the American Thoracic Society, Volume 15, Issue 4, Page 432-439, April 2018.
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Is It Time to “Go With the (High) Flow”?
https://ift.tt/2GWQc4P
Is It Time to Consider Obstructive Sleep Apnea Syndrome a Risk Factor for Alzheimer’s Disease?
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 855-856, April 1, 2018.
https://ift.tt/2GZ9dno
Exosome Treatment of Bronchopulmonary Dysplasia: How Pure Should Your Exosome Preparation Be?
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 969-970, April 1, 2018.
https://ift.tt/2uvyz9T
Breaking the In Vitro Barrier in Respiratory Medicine. Engineered Microphysiological Systems for Chronic Obstructive Pulmonary Disease and Beyond
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 869-875, April 1, 2018.
https://ift.tt/2H00kKs
Tobacco Smoking Is a Medical Problem. We Ought to Treat It Like One
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 852-853, April 1, 2018.
https://ift.tt/2E44spz
An Observational Study of the Efficacy of Cisatracurium Compared with Vecuronium in Patients with or at Risk for Acute Respiratory Distress Syndrome
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 897-904, April 1, 2018.
https://ift.tt/2GYbbVb
What Is Laryngomalacia?
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page P11-P12, April 1, 2018.
https://ift.tt/2uvyfYJ
Erratum: Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 971-971, April 1, 2018.
https://ift.tt/2GXM1pn
Y Not? Sex Chromosomes May Modify Sexual Dimorphism in Pulmonary Hypertension
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 858-859, April 1, 2018.
https://ift.tt/2uxvTZo
Erratum: Effects of Age and Disease Severity on Systemic Corticosteroid Responses in Asthma
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 970-971, April 1, 2018.
https://ift.tt/2H00gKI
The Significance of Eosinophilic Inflammation in Chronic Obstructive Pulmonary Disease
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 967-968, April 1, 2018.
https://ift.tt/2uvgb0K
Reply to Muraca et al.: Exosome Treatment of Bronchopulmonary Dysplasia: How Pure Should Your Exosome Preparation Be?
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 970-970, April 1, 2018.
https://ift.tt/2GZ89zR
Increased Echocardiographic Pulmonary Pressure in HIV-infected and -uninfected Individuals in the Veterans Aging Cohort Study
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 923-932, April 1, 2018.
https://ift.tt/2uyLAzx
Airway Epithelial Progenitors and the Natural History of Chronic Obstructive Pulmonary Disease
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 847-849, April 1, 2018.
https://ift.tt/2GZ88fh
Precision Medicine in Asthma: Integrating Imaging and Inflammatory Biomarkers
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 845-846, April 1, 2018.
https://ift.tt/2E7YNi6
Is It Acceptable to Assess Prenatal Smoking Risk to Infants without Considering Socioeconomic Status?
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 965-966, April 1, 2018.
https://ift.tt/2GZCG0g
Reply to Cooper et al.: The Significance of Eosinophilic Inflammation in Chronic Obstructive Pulmonary Disease
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 968-969, April 1, 2018.
https://ift.tt/2uugvwE
Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly. A Longitudinal Study
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 933-943, April 1, 2018.
https://ift.tt/2GYCQVI
Reply to Vaz Fragoso et al.: Spirometry-based Diagnostic Criteria That Are Not Age-Appropriate Lack Clinical Relevance
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 964-965, April 1, 2018.
https://ift.tt/2E6aZ35
Seeing Deeply into the Lung in Interstitial Lung Disease
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 857-858, April 1, 2018.
https://ift.tt/2GWMmJ0
Cardiovascular and Neuropsychiatric Events after Varenicline Use for Smoking Cessation
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 913-922, April 1, 2018.
https://ift.tt/2uDhj2G
Outcome prediction in patients with acute repetitive seizures: Application of the Status Epilepticus Severity Score
Epilepsia, EarlyView.
https://ift.tt/2GXJ6wV
SCN1A variants associated with sudden infant death syndrome
Epilepsia, EarlyView.
https://ift.tt/2E7WETA
Depression comorbidity in epileptic rats is related to brain glucose hypometabolism and hypersynchronicity in the metabolic network architecture
Epilepsia, EarlyView.
https://ift.tt/2H2yWvn
Radiosurgery versus open surgery for mesial temporal lobe epilepsy: The randomized, controlled ROSE trial
Epilepsia, EarlyView.
https://ift.tt/2uww1sb
IL-33 induced inflammation exacerbated the development of chronic obstructive pulmonary disease through oxidative stress
OBJECTIVE: We aimed at exploring the role of IL-33 in mouse chronic obstructive pulmonary disease and its potential molecular mechanism.
MATERIALS AND METHODS: The chronic obstructive pulmonary disease (COPD) mice model was established by cigarette smoking (CS). COPD mice were randomly assigned into PBS group and IL-33 antibody group. The peripheral blood and lung tissues of mice from two groups were collected for the following experiments. Pathological changes of the lung tissues in both groups were analyzed by hematoxylin and eosin (HE) staining. IL-33 positive cells in lung tissues were detected by immunohistochemistry. Then, the mRNA and protein levels of IL-33, sST2, ERK and TNF-α in the mice peripheral blood of the two groups were accessed by Real-time polymerase chain reaction (RT-PCR) and Western blot. Finally, the indicators related to oxidative stress, including superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) in the mice serum of two groups were measured.
RESULTS: After successful construction of COPD mouse model by CS, HE staining illustrated that the structure of airway wall of lung tissue in mice from PBS group was irregular. The ciliated columnar epithelium presented significant degeneration, necrosis and shedding. A large amount of inflammation cell infiltration was observed in vascular tissues. The alveolar epithelial structure was severely damaged and alveolar septum was narrowed and ruptured. Adjacent alveoli were found to be fused into larger cysts. The above pathological changes were relatively better in mice from IL-33 antibody group. Immunohistochemical results demonstrated that IL-33 was remarkably deposited in the lung tissue of PBS group. The mRNA and protein levels of IL-33, sST2, ERK and TNF-α in peripheral blood of PBS group were much higher than those of IL-33 antibody group. At the same time, SOD level in PBS group decreased, while MDA level and ROS production increased.
CONCLUSIONS: IL-33 aggravates lung injury in COPD mice by increasing inflammation response and oxidative stress, which may serve as a target for predicting and treating COPD.
L'articolo IL-33 induced inflammation exacerbated the development of chronic obstructive pulmonary disease through oxidative stress sembra essere il primo su European Review.
https://ift.tt/2GlyGGA
The relationship between Muc5ac high secretion and Munc18b upregulation in obese asthma
OBJECTIVE: Mucus production and hypersecretion are important pathophysiological features of asthma. Airway mucus secretion is more serious in obese asthma. Therefore, it is of great significance to elucidate the mechanism of asthma airway mucus high secretion in improving the control of asthma and the prognosis of obese asthmatic patients.
MATERIALS AND METHODS: Obese asthmatic mice model was established to test the airway resistance and mucin secretion by hematoxylin-eosin (HE) staining. Munc18b and Muc5ac expression levels were determined by Western-blotting. Munc18b conditioned knockout mice were adopted to explore the mechanism of Muc5ac high secretion.
RESULTS: The mice weight increased in obese asthmatic model accompanied by elevated airway resistance. HE staining showed enhanced mucin secretion, which was correlated to weight and airway resistance. Munc18b and Muc5ac expressions significant upregulated in an obese asthmatic mouse model compared with normal control. Muc5ac expression failed to show elevation in Munc18b conditioned knockout mice.
CONCLUSIONS: Muc5ac high secretion was positively correlated with Munc18b upregulation in obese asthma. Munc18b participated in inducing Muc5ac high expression.
L'articolo The relationship between Muc5ac high secretion and Munc18b upregulation in obese asthma sembra essere il primo su European Review.
https://ift.tt/2GGkUS8
Expression of Nrf2-Keap1-ARE signal pathway in traumatic lung injury and functional study
OBJECTIVE: Traumatic lung injury (TLI) can cause inflammation and oxidative stress, or even leads to acute respiratory distress syndrome (ARDS) and death. Nuclear factor erythroid-2 related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signal pathway participates in disease occurrence and progression via regulating inflammatory and oxidative stress response, but with its expression and functional roles in TLI largely unknown.
MATERIALS AND METHODS: Wistar rats were randomly divided into control group, TLI group by crushing method, and Nrf2 activation group which received Nrf2 specific agonist sulforaphane 30 min before TLI treatment. Artery blood gas (ABG), wet/dry mass ratio (W/D) of lung tissues, myeloid peroxidase (MPO) and superoxide dismutase (SOD) activity of lung tissue were analyzed. Keap1 and ARE mRNA levels were tested by Real-time PCR, while Nrf2 protein was measured by Western blot. Inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) were quantified by enzyme-linked immunosorbent assay (ELISA).
RESULTS: TLI model had lower ABG or SOD, higher W/D ratio, MPO value, elevated expressions of TNF-α, IL-2, and Keap1, plus decreased Nrf2 and ARE expression (p<0.05). Nrf2 activation significantly improved ABG, decreased W/D ratio and MPO value, enhanced SOD activity, decreased TNF-α and IL-2 secretion, suppressed Keap1 expression, and facilitated Nrf2 and ARE expressions (p<0.05).
CONCLUSIONS: Nrf2-Keap1-ARE signal pathway can improve TLI-related pathology via modulating oxidative stress response and suppressing inflammation.
L'articolo Expression of Nrf2-Keap1-ARE signal pathway in traumatic lung injury and functional study sembra essere il primo su European Review.
https://ift.tt/2GnTf5f
Carbon Dots: Near‐Infrared Excitation/Emission and Multiphoton‐Induced Fluorescence of Carbon Dots (Adv. Mater. 13/2018)
Advanced Materials, Volume 30, Issue 13, March 27, 2018.
https://ift.tt/2E6M1AF
Single‐Atom Catalysts: Atomically Dispersed Transition Metals on Carbon Nanotubes with Ultrahigh Loading for Selective Electrochemical Carbon Dioxide Reduction (Adv. Mater. 13/2018)
Advanced Materials, Volume 30, Issue 13, March 27, 2018.
https://ift.tt/2GZTkNG
Adaptive Soft Robots: Soft Ultrathin Electronics Innervated Adaptive Fully Soft Robots (Adv. Mater. 13/2018)
Advanced Materials, Volume 30, Issue 13, March 27, 2018.
https://ift.tt/2GWxnPm
Phonon Polaritons: Highly Confined and Tunable Hyperbolic Phonon Polaritons in Van Der Waals Semiconducting Transition Metal Oxides (Adv. Mater. 13/2018)
Advanced Materials, Volume 30, Issue 13, March 27, 2018.
https://ift.tt/2uvtgHv
Cancer Therapy: A Magnetofluorescent Carbon Dot Assembly as an Acidic H2O2‐Driven Oxygenerator to Regulate Tumor Hypoxia for Simultaneous Bimodal Imaging and Enhanced Photodynamic Therapy (Adv. Mater. 13/2018)
Advanced Materials, Volume 30, Issue 13, March 27, 2018.
https://ift.tt/2GXb8ZI
An Alkylated Indacenodithieno[3,2‐b]thiophene‐Based Nonfullerene Acceptor with High Crystallinity Exhibiting Single Junction Solar Cell Efficiencies Greater than 13% with Low Voltage Losses
Advanced Materials, Volume 30, Issue 13, March 27, 2018.
https://ift.tt/2uCaXAq
Risk Assessment Tools in Pulmonary Arterial Hypertension. Prognosis for Prospective Trials?
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 843-845, April 1, 2018.
https://ift.tt/2uyPYyy
Does HIV Really Augment the Frequency or Mortality Risk of Increased Pulmonary Artery Systolic Pressures?
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 854-855, April 1, 2018.
https://ift.tt/2GlJfgL
Chronic Obstructive Pulmonary Disease: Recent Advances and Controversies in Inhaler Therapies
American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 7, Page 944-946, April 1, 2018.
https://ift.tt/2uxryFH
A cross-sectional survey of physical strains among offshore wind farm workers in the German exclusive economic zone
Objectives
To assess the physical strains of employees in the German offshore wind industry, according to job type and phase of the wind farm (under construction or operation).
DesignWeb-based cross-sectional survey.
SettingOffshore wind farm companies operating within the German exclusive economic zone.
ParticipantsMale workers with regular offshore commitments and at least 28 days spent offshore in the past year (n=268).
Outcome measuresPhysical strains (eg, climbing, noise, working overhead, with twisted upper body or in confined spaces, vibration, heavy lifting, humidity, odours).
ResultsThe most frequently mentioned physical strain was 'climbing' with 63.8% of the respondents reporting to be always or frequently confronted with climbing and ascending stairs during offshore work. Work as a technician was associated with a greater exposition to noise, vibrations, humidity, cold, heat, chemical substances, lifting/carrying heavy loads, transport of equipment, working in non-ergonomic positions and in cramped spaces, as well as climbing.
Indeed, statistical analyses showed that, after adjusting for phase of the wind farm, age, nationality, offshore experience, work schedule and type of shift, compared with non-technicians, working as a technician was associated with more frequently lifting/carrying of heavy loads (OR 2.58, 95% CI 1.58 to 4.23), transport of equipment (OR 2.06 95% CI 1.27 to 3.33), working with a twisted upper body (OR 2.85 95% CI 1.74 to 4.69), working overhead (OR 2.77 95% CI 1.67 to 4.58) and climbing (OR 2.30 95% CI 1.40 to 3.77). Working in wind farms under construction was strongly associated with increased and decreased exposure to humidity (OR 2.32 95% CI 1.38 to 3.92) and poor air quality (OR 0.58 95% CI 0.35 to 0.95), respectively.
ConclusionsWorkers on offshore wind farms constitute a heterogeneous group, including a wide variety of occupations. The degree of exposure to detrimental physical strains varies depending on the type of job. Technicians are more exposed to ergonomic challenges than other offshore workers.
https://ift.tt/2pOxynI
Dentists intention to report suspected violence: a cross-sectional study in eight Arab countries
Objectives
This study assessed dentists' intention in eight Arab countries to report suspected exposure to violence among patients and factors associated with this intention based on the theory of planned behaviour.
MethodsA cross-sectional study was conducted in 2016 including a convenience sample of dentists practising in public, private and academic sectors in Algeria, Egypt, Jordan, Kuwait, Libya, Palestine, Saudi Arabia and Yemen. Respondents answered a self-administered questionnaire collecting information about personal and professional background and perceived ability to identify victims of violence. The questionnaire assessed (on a scale from 1 to 10 using six negative statements) dentists' perception of healthcare system mandated reporting of suspected violence. Six statements were used to assess professional attitude towards reporting suspected violence. Logistic regression was used to assess the association between intention to report suspected violence and perceived ability, perception and attitude adjusting for confounders.
ResultsThe response rate was 65.2% (n=2936/4506) from general practitioners (70.9%) of mean age=31 years with 56.7% women. Of those, 68.8% intended to report and 52.2% considered themselves able to identify violence victims. The mean (SD) negative perception score=5.3/10 (2.1) and the mean (SD) professional attitude score=7.5/10 (1.9). In multivariate regression, intention to report was associated with professional attitude (OR 1.08, 95% CI 1.03 to 1.14), ability to identify violence victims (OR 1.76, 95% CI 1.45 to 2.12) and negative perception that reporting is not mandated (OR 0.89, 95% CI 0.85 to 0.94). Significant differences existed among countries in intention to report.
ConclusionMost dentists intended to report suspected violence and their intention could be explained by the theory of planned behaviour which offers a framework for professional development to support violence victims. Sharing of training resources, policies and guidelines is needed to ensure that practices similar to international guidelines are consistently adopted by dentists across Arab countries.
https://ift.tt/2J7wT9F
Distribution and predictors of hospital charges for haemorrhagic stroke patients in Beijing, China, March 2012 to February 2015: a retrospective study
Objectives
The purpose of this study is to analyse hospital charges for patients with haemorrhagic stroke in China and investigate potential factors associated with inpatient charges.
MethodsThe study participants were in-hospital patients with a primary diagnosis of haemorrhagic stroke from all the secondary and tertiary hospitals in Beijing during the period from 1 March 2012 to 28 February 2015. Distribution characteristics of detailed hospital charges were analysed. The influence of potential factors on hospital charges was researched using a stepwise multiple regression model.
ResultsA total of 34 890 patients with haemorrhagic stroke of mean age 61.19±14.37 years were included in the study, of which 37.2% were female. Median length of hospital stay (LOHS) was 15 days (IQR 9–23) and median hospital cost was 18 577 Chinese yuan (CNY) (IQR 10 442–39 784). The hospital costs for patients in Western medicine hospitals (median 19 651 CNY) were significantly higher (P<0.01) than those in traditional Chinese medicine hospitals (median 14 560 CNY), and were significantly higher (P<0.01) for Level 3 hospitals (median 20 029 CNY) than for Level 2 hospitals (median 16 095 CNY). The proportion of medicine fees and bed fees within total hospital charges showed a decreasing trend during the study period. With stepwise multiple regression, the major factors associated with hospital charges were LOHS, surgery, pulmonary infection, ventilator usage, hospital level, occupation, hyperlipidaemia, hospital type, in-hospital death, sex and age.
ConclusionWe conclude that medicines form the largest part of hospital charges but are showing a decreasing trend, and LOHS is strongly associated with patient charges for haemorrhagic stroke in China. This implies that the cost structure is very unreasonable in China and medical technology costs fail to be fully manifested. A reasonable decrease in medicine charges and shortening LOHS may be effective ways to reduce hospital charges.
https://ift.tt/2pSZMxP
Dementia and vagotomy in Taiwan: a population-based cohort study
Objective
Truncal vagotomy is associated with a decreased risk of subsequent Parkinson disease (PD), although the effect of vagotomy on dementia is unclear. In response, we investigated the risk of dementia in patients who underwent vagotomy.
SettingPopulation-based cohort study.
ParticipantsA total of 155 944 patients who underwent vagotomy (vagotomy cohort) and 155 944 age-matched, sex-matched and comorbidity-matched controls (non-vagotomy cohort) were identified between 2000 and 2011.
Primary and secondary outcome measuresAll patient data were tracked until the diagnosis of dementia, death or the end of 2011. The cumulative incidence of subsequent dementia and HRs were calculated.
ResultsThe mean ages of the study patients in the vagotomy and non-vagotomy cohorts were 56.6±17.4 and 56.7±17.3 years, respectively. The overall incidence density rate for dementia was similar in the vagotomy and non-vagotomy cohorts (2.43 and 2.84 per 1000 person-years, respectively). After adjustment for age, sex and comorbidities such as diabetes, hypertension, hyperlipidaemia, stroke, depression, coronary artery disease and PD, the patients in the vagotomy cohort were determined to not be at a higher risk of dementia than those in the non-vagotomy cohort (adjusted HR=1.09, 95% CI 0.87 to 1.36). Moreover, the patients who underwent truncal vagotomy were not associated with risk of dementia (adjusted HR=1.04, 95% CI 0.87 to 1.25), compared with the patients who did not undergo vagotomy.
ConclusionVagotomy, either truncal or selective, is not associated with risk of dementia.
https://ift.tt/2J5q9ct
Trends in initiation of direct oral anticoagulant therapies for atrial fibrillation in a national population-based cross-sectional study in the French health insurance databases
Objective
Unlike several other national health agencies, French health authorities recommended that the newer direct oral anticoagulant (DOAC) agents only be prescribed as second choice for the treatment of newly diagnosed non-valvular atrial fibrillation (NVAF), with vitamin K antagonists (VKA) remaining the first choice. We investigated the patterns of use of DOACs versus VKA in the treatment of NVAF in France over the first 5 years of DOAC availability. We also identified the changes in patient characteristics of those who initiated DOAC treatment over this time period.
MethodsBased on the French National Health Administrative Database, we constituted a population-based cohort of all patients who were newly treated for NVAF between January 2011 and December 2015. Trends in drug use were described as the percentage of patients initiating each drug at the time of treatment initiation. A multivariate analysis using logistic regression model was performed to identify independent sociodemographic and clinical predictors of initial anticoagulant choice.
ResultsThe cohort comprised 814 446 patients who had received a new anticoagulant treatment for NVAF. The proportion of patients using DOACs as initial anticoagulant therapy reached 54% 3 months after the Health Ministry approved the reimbursement of dabigatran for NVAF, and 61% by the end of 2015, versus VKA use. In the multivariate analysis, we found that DOAC initiators were younger and healthier overall than VKA initiators, and this tendency was reinforced over the 2011–2014 period. DOACs were more frequently prescribed by cardiologists in 2012 and after (adjusted OR in 2012: 2.47; 95% CI 2.40 to 2.54).
ConclusionDespite recommendations from health authorities, DOACs have been rapidly and massively adopted as initial therapy for NVAF in France. Observational studies should account for the fact that patients selected to initiate DOAC treatment are healthier overall, as failure to do so may bias the risk–benefit assessment of DOACs.
https://ift.tt/2pSNWUf
Protocol for the mixed-methods process and context evaluation of the TB & Tobacco randomised controlled trial in Bangladesh and Pakistan: a hybrid effectiveness-implementation study
Introduction
Tuberculosis (TB) remains a significant public health problem in South Asia. Tobacco use increases the risks of TB infection and TB progression. The TB& Tobacco placebo-controlled randomised trial aims to (1) assess the effectiveness of the tobacco cessation medication cytisine versus placebo when combined with behavioural support and (2) implement tobacco cessation medication and behavioural support as part of general TB care in Bangladesh and Pakistan. This paper summarises the process and context evaluation protocol embedded in the effectiveness–implementation hybrid design.
Methods and analysisWe are conducting a mixed-methods process and context evaluation informed by an intervention logic model that draws on the UK Medical Research Council's Process Evaluation Guidance. Our approach includes quantitative and qualitative data collection on context, recruitment, reach, dose delivered, dose received and fidelity. Quantitative data include patient characteristics, reach of recruitment among eligible patients, routine trial data on dose delivered and dose received, and a COM-B ('capability', 'opportunity', 'motivation' and 'behaviour') questionnaire filled in by participating health workers. Qualitative data include semistructured interviews with TB health workers and patients, and with policy-makers at district and central levels in each country. Interviews will be analysed using the framework approach. The behavioural intervention delivery is audio recorded and assessed using a predefined fidelity coding index based on behavioural change technique taxonomy.
Ethics and disseminationThe study complies with the guidelines of the Declaration of Helsinki. Ethics approval for the study and process evaluation was granted by the University of Leeds (qualitative components), University of York (trial data and fidelity assessment), Bangladesh Medical Research Council and Bangladesh Drug Administration (trial data and qualitative components) and Pakistan Medical Research Council (trial data and qualitative components). Results of this research will be disseminated through reports to stakeholders and peer-reviewed publications and conference presentations.
Trial registration numberISRCTN43811467; Pre-results.
https://ift.tt/2J8UYwT
Measuring quality of life of people with predementia and dementia and their caregivers: a systematic review protocol
Introduction
Dementia is the fastest growing major cause of disability globally and may have a profound impact on the health-related quality of life (HRQoL) of both the patient with dementia and those who care for them. This review aims to systematically identify and synthesise the measurements of HRQoL for people with, and their caregivers across the full spectrum of, dementia from its preceding stage of predementia to end of life.
Methods and analysisA systematic literature review was conducted in Medical Literature Analysis and Retrieval System Online , ExcerptaMedicadataBASE, Cochrane Database of Systematic Reviews , Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effect, National Health Service Economic Evaluation Database and PsycINFO between January 1990 and the end of April 2017. Two reviewers will independently assess each study for inclusion and disagreements will be resolved by a third reviewer. Data will be extracted using a predefined data extraction form following best practice. Study quality will be assessed with the Effective Public Health Practice Project quality assessment tool. HRQoL measurements will be presented separately for people with dementia and caregivers by instrument used and, when possible, HRQoL will be reported by disease type and stage of the disease. Descriptive statistics of the results will be provided. A narrative synthesis of studies will also be provided discussing differences in HRQoL measurements by instrument used to estimate it, type of dementia and disease severity.
Ethics and disseminationThis systematic literature review is exempt from ethics approval because the work is carried out on published documents. The findings of the review will be disseminated in a related peer-reviewed journal and presented at conferences. They will also contribute to the work developed in the Real World Outcomes across the Alzheimer's disease spectrum for better care: multimodal data access platform (ROADMAP).
Trial registration numberhttps://ift.tt/2pSxmnm
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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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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
