Objectives: Platelet defect mechanisms after cardiopulmonary bypass remain unclear. Our hypothesis microRNA expressions in circulating platelets significantly change between pre and post cardiopulmonary bypass, and consequent messenger RNA and protein expression level alterations cause postcardiopulmonary bypass platelet defect. Design: Single-center prospective observational study. Setting: Operating room of Kyoto Prefectural University of Medicine. Patients: Twenty-five adult patients scheduled for elective cardiac surgeries under cardiopulmonary bypass. Interventions: None. Measurements and Main Results: In the initial phase, changes in microRNA expression between pre and post cardiopulmonary bypass underwent next generation sequencing analysis (10 patients). Based on the results, we focused on changes in mir-10b and mir-96, which regulate glycoprotein 1b and vesicle-associated membrane protein 8, respectively, and followed them until messenger RNA and protein syntheses (15 patients) using quantitative polymerase chain reaction and Western blotting. Seven microRNAs including mir-10b and mir-96 exhibited significant differences in the initial phase. In the subsequent phase, mir-10b-5p and mir-96-5p overexpressions were confirmed, and glycoprotein 1b and vesicle-associated membrane protein 8 messenger RNA levels were significantly decreased after cardiopulmonary bypass: fold differences (95% CI): mir-10b-5p: 1.35 (1.05–2.85), p value equals to 0.01; mir-96-5p: 1.59 (1.06–2.13), p value equals to 0.03; glycoprotein 1b messenger RNA: 0.46 (0.32–0.60), p value of less than 0.001; and vesicle-associated membrane protein messenger RNA: 0.70 (0.56–0.84), p value of less than 0.001. Glycoprotein 1b and vesicle-associated membrane protein 8 were also significantly decreased after cardiopulmonary bypass: glycoprotein 1b: 82.6% (71.3–93.8%), p value equals to 0.005; vesicle-associated membrane protein 8: 79.0% (70.7–82.3%), p value of less than 0.001. Conclusions: Expressions of several microRNAs in circulating platelets significantly changed between pre and post cardiopulmonary bypass. Overexpressions of mir-10b and mir-96 decreased glycoprotein 1b and vesicle-associated membrane protein 8 messenger RNA as well as protein, possibly causing platelet defect after cardiopulmonary bypass. Drs. Mukai and Nakayama contributed equally to this work. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by the Grant-in-Aids for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (numbers 26462761, 26462370, 17K11093, 17K11094). The authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Yoshinobu Nakayama, MD, PhD, Department of Anesthesiology and Critical Care, Kyoto Prefectural University of Medicine, Kajiicho 465, Kamigyo-Ku, Kyoto, Japan. E-mail: na-yoshi@koto.kpu-m.ac.jp Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
https://ift.tt/2wrJHpb
Τετάρτη 9 Μαΐου 2018
Predictive Validity of Sepsis-3 Definitions and Sepsis Outcomes in Critically Ill Patients: A Cohort Study in 49 ICUs in Argentina
Objectives: The new Sepsis-3 definitions have been scarcely assessed in low- and middle-income countries; besides, regional information of sepsis outcomes is sparse. Our objective was to evaluate Sepsis-3 definition performance in Argentina. Design: Cohort study of 3-month duration beginning on July 1, 2016. Settings: Forty-nine ICUs. Patients: Consecutive patients admitted to the ICU with suspected infection that triggered blood cultures and antibiotic administration. Interventions: None. Measurements and Main Results: Patients were classified as having infection, sepsis (infection + change in Sequential Organ Failure Assessment ≥ 2 points), and septic shock (vasopressors + lactate > 2 mmol/L). Patients on vasopressors and lactate less than or equal to 2 mmol/L (cardiovascular dysfunction) were analyzed separately, as those on vasopressors without serum lactate measurement. Systemic inflammatory response syndrome was also recorded. Main outcome was hospital mortality. Of 809 patients, 6% had infection, 29% sepsis, 20% cardiovascular dysfunction, 40% septic shock, and 3% received vasopressors with lactate unmeasured. Hospital mortality was 13%, 20%, 39%, 51%, and 41%, respectively (p = 0.000). Independent predictors of outcome were lactate, Sequential Organ Failure Assessment score, comorbidities, prior duration of symptoms (hr), mechanical ventilation requirement, and infection by highly resistant microorganisms. Area under the receiver operating characteristic curves for mortality for systemic inflammatory response syndrome and Sequential Organ Failure Assessment were 0.53 (0.48–0.55) and 0.74 (0.69–0.77), respectively (p = 0.000). Conclusions: Increasing severity of Sepsis-3 categories adequately tracks mortality; cardiovascular dysfunction subgroup, not included in Sepsis-3, has distinct characteristics. Sequential Organ Failure Assessment score shows adequate prognosis accuracy─contrary to systemic inflammatory response syndrome. This study supports the predictive validity of Sepsis-3 definitions. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by a grant of the National Ministry of Health (2014) given to the Sociedad Argentina de Terapia Intensiva. Dr. Pálizas disclosed government work and disclosed that this research was organized by a Committee of the Argentine Society of Critical Care Medicine (SATI); SATI received some funding from the Ministry of Health due to the epidemiologic importance of the study. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: estenssoro.elisa@gmail.com Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
https://ift.tt/2Kaaokm
https://ift.tt/2Kaaokm
Cardiac Arrest in Patients Managed for Convulsive Status Epilepticus: Characteristics, Predictors, and Outcome
Objectives: Cardiac arrest is a catastrophic event that may arise during the management of convulsive status epilepticus. We aimed to report the clinical characteristics, outcomes, and early predictors of convulsive status epilepticus–related cardiac arrest. Design: Retrospective multicenter study. Setting: Seventeen university or university affiliated participating ICUs in France and Belgium. Patients: Consecutive patients admitted to the participating ICUs for management of successfully resuscitated out-of-hospital cardiac arrest complicating the initial management of convulsive status epilepticus between 2000 and 2015. Patients were compared with controls without cardiac arrest identified in a single-center registry of convulsive status epilepticus patients, regarding characteristics, management, and outcome. Interventions: None. Measurements and Main Results: We included 49 cases with convulsive status epilepticus–cardiac arrest and 235 controls. In the cases, median time from medical team arrival to cardiac arrest was 25 minutes (interquartile range, 5–85 min). First recorded rhythm was asystole in 25 patients (51%) and pulseless electrical activity in 13 patients (27%). A significantly larger proportion of patients had a favorable 1-year outcome (Glasgow Outcome Scale score of 5) among controls (90/235; 38%) than among cases (10/49; 21%; p = 0.02). By multivariate analysis, independent predictors of cardiac arrest were pulse oximetry less than 97% on scene (odds ratio, 2.66; 95% CI, 1.03–7.26; p = 0.04), drug poisoning as the cause of convulsive status epilepticus (odds ratio, 4.13; 95% CI, 1.27–13.53; p = 0.02), and complications during early management (odds ratio, 11.98; 95% CI, 4.67–34.69; p
https://ift.tt/2rx8ALm
https://ift.tt/2rx8ALm
Long-Term Survival of Young Patients Surviving ICU Admission With Severe Sepsis
Objectives: Sepsis remains a disease with a high mortality rate. The study goal was to assess long-term survival of severe sepsis in young patients. Design: Retrospective cohort study. Setting: Patients admitted with sepsis to ICUs in seven tertiary hospitals between 2003 and 2011. Patients: A total of 409 patients less than 45 years who survived to hospital discharge were age and sex matched with 818 patients with infectious disease without sepsis selected from internal medicine or surgical department admissions. Interventions: None. Measurements and Main Results: The median age in sepsis patients and the comparison group was 31 and 32 years, respectively. The proportions of patients surviving after hospital discharge were significantly lower in the sepsis group compared with the control group; among survivors, 6-month, 1-year, and 3-year mortality rates were 0.7% versus 0%, 4.5% versus 0.7%, 7.9% versus 1.2%, and 10.8% versus 1.8%, respectively (p
https://ift.tt/2K7kuCu
https://ift.tt/2K7kuCu
Exploratory Application of Neuropharmacometabolomics in Severe Childhood Traumatic Brain Injury
Objectives: To employ metabolomics-based pathway and network analyses to evaluate the cerebrospinal fluid metabolome after severe traumatic brain injury in children and the capacity of combination therapy with probenecid and N-acetylcysteine to impact glutathione-related and other pathways and networks, relative to placebo treatment. Design: Analysis of cerebrospinal fluid obtained from children enrolled in an Institutional Review Board–approved, randomized, placebo-controlled trial of a combination of probenecid and N-acetylcysteine after severe traumatic brain injury (Trial Registration NCT01322009). Setting: Thirty-six–bed PICU in a university-affiliated children's hospital. Patients and Subjects: Twelve children 2–18 years old after severe traumatic brain injury and five age-matched control subjects. Intervention: Probenecid (25 mg/kg) and N-acetylcysteine (140 mg/kg) or placebo administered via naso/orogastric tube. Measurements and Main Results: The cerebrospinal fluid metabolome was analyzed in samples from traumatic brain injury patients 24 hours after the first dose of drugs or placebo and control subjects. Feature detection, retention time, alignment, annotation, and principal component analysis and statistical analysis were conducted using XCMS-online. The software "mummichog" was used for pathway and network analyses. A two-component principal component analysis revealed clustering of each of the groups, with distinct metabolomics signatures. Several novel pathways with plausible mechanistic involvement in traumatic brain injury were identified. A combination of metabolomics and pathway/network analyses showed that seven glutathione-centered pathways and two networks were enriched in the cerebrospinal fluid of traumatic brain injury patients treated with probenecid and N-acetylcysteine versus placebo-treated patients. Several additional pathways/networks consisting of components that are known substrates of probenecid-inhibitable transporters were also identified, providing additional mechanistic validation. Conclusions: This proof-of-concept neuropharmacometabolomics assessment reveals alterations in known and previously unidentified metabolic pathways and supports therapeutic target engagement of the combination of probenecid and N-acetylcysteine treatment after severe traumatic brain injury in children. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by the National Institutes of Health grants R01 NS069247 (to Drs. Empey, Bell, and Clark), 1TL1 TR001858-01 (to Dr. Hagos). Mr. Hagos, Drs. Empey, Poloyac, Bayir, Bell, and Clark received support for article research from the National Institutes of Health (NIH). Mr. Hagos received funding from NIH and University of Pittsburgh Clinical and Translational Science Institute. Mr. Hagos, Drs. Empey, and Bell disclosed off-label product use of probenecid and N-acetylcysteine for pediatric traumatic brain injury. Drs. Empey's, Kochanek's, and Bell's institutions received funding from the NIH. Dr. Kochanek received funding from Society of Critical Care Medicine and World Federation of Pediatric Intensive and Critical Care Societies (Editor-in-Chief of Pediatric Critical Care Medicine) and he has served as an expert witness on a number of cases and has given numerous lectures as a guest professor. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: clarkrs@ccm.upmc.edu; pempey@pitt.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
https://ift.tt/2ryzkeg
https://ift.tt/2ryzkeg
Derivation and Validation of a Biomarker-Based Clinical Algorithm to Rule Out Sepsis From Noninfectious Systemic Inflammatory Response Syndrome at Emergency Department Admission: A Multicenter Prospective Study
Objectives: To derive and validate a predictive algorithm integrating a nomogram-based prediction of the pretest probability of infection with a panel of serum biomarkers, which could robustly differentiate sepsis/septic shock from noninfectious systemic inflammatory response syndrome. Design: Multicenter prospective study. Setting: At emergency department admission in five University hospitals. Patients: Nine-hundred forty-seven adults in inception cohort and 185 adults in validation cohort. Interventions: None. Measurements and Main Results: A nomogram, including age, Sequential Organ Failure Assessment score, recent antimicrobial therapy, hyperthermia, leukocytosis, and high C-reactive protein values, was built in order to take data from 716 infected patients and 120 patients with noninfectious systemic inflammatory response syndrome to predict pretest probability of infection. Then, the best combination of procalcitonin, soluble phospholypase A2 group IIA, presepsin, soluble interleukin-2 receptor α, and soluble triggering receptor expressed on myeloid cell-1 was applied in order to categorize patients as "likely" or "unlikely" to be infected. The predictive algorithm required only procalcitonin backed up with soluble phospholypase A2 group IIA determined in 29% of the patients to rule out sepsis/septic shock with a negative predictive value of 93%. In a validation cohort of 158 patients, predictive algorithm reached 100% of negative predictive value requiring biomarker measurements in 18% of the population. Conclusions: We have developed and validated a high-performing, reproducible, and parsimonious algorithm to assist emergency department physicians in distinguishing sepsis/septic shock from noninfectious systemic inflammatory response syndrome. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by the Italian Ministry of Health. Drs. Mearelli, Fiotti, Giansante, Casarsa, De Helmersen, Altamura, Barbati, and Bregnocchi disclosed government work. Dr. Orso received support for article research from the Italian Ministry of Education, Universities and Research. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: filippome@libero.it Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
https://ift.tt/2rwV9ee
https://ift.tt/2rwV9ee
Clinical Factors Associated With ICU-Specific Care Following Supratentoral Brain Tumor Resection and Validation of a Risk Prediction Score
Objectives: The postoperative management of patients who undergo brain tumor resection frequently occurs in an ICU. However, the routine admission of all patients to an ICU following surgery is controversial. This study seeks to identify the frequency with which patients undergoing elective supratentorial tumor resection require care, aside from frequent neurologic checks, that is specific to an ICU and to determine the frequency of new complications during ICU admission. Additionally, clinical predictors of ICU-specific care are identified, and a scoring system to discriminate patients most likely to require ICU-specific treatment is validated. Design: Retrospective observational cohort study. Setting: Academic neurosurgical center. Patients: Two-hundred consecutive adult patients who underwent supratentorial brain tumor surgery. An additional 100 consecutive patients were used to validate the prediction score. Interventions: None. Measurements and Main Results: Univariate statistics and multivariable logistic regression were used to identify clinical characteristics associated with ICU-specific treatment. Eighteen patients (9%) received ICU-specific care, and 19 (9.5%) experienced new complications or underwent emergent imaging while in the ICU. Factors significantly associated with ICU-specific care included nonelective admission, preoperative Glasgow Coma Scale, and volume of IV fluids. A simple clinical scoring system that included Karnofsky Performance Status less than 70 (1 point), general endotracheal anesthesia (1 point), and any early postoperative complications (2 points) demonstrated excellent ability to discriminate patients who required ICU-specific care in both the derivation and validation cohorts. Conclusions: Less than 10% of patients required ICU-specific care following supratentorial tumor resection. A simple clinical scoring system may aid clinicians in stratifying the risk of requiring ICU care and could inform triage decisions when ICU bed availability is limited. This work was performed at the University of Michigan, Ann Arbor, MI. Presented, in part, as an electronic poster at the American Association of Neurological Surgeons Annual Meeting 2017, Los Angeles, CA. Ms. Franko and Dr. Hollon contributed equally to this work. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Ms. Franko received grant funding from the Student Biomedical Research Program at the University of Michigan School of Medicine to complete this research ($4,870 for 10 wk of dedicated time to work on the project as a medical student researcher). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: craigaw@med.umich.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
https://ift.tt/2wz2M9c
https://ift.tt/2wz2M9c
A Multicenter Observational Study of Family Participation in ICU Rounds
Objectives: Guidelines recommend offering family members of critically ill patients the option to attend interdisciplinary team rounds as a way to improve communication and satisfaction. Uncertainty remains around the benefits and risks. Design: We conducted an observational study to describe family participation in ICU rounds and its association with rounding processes. Setting: Rounds conducted under the leadership of 33 attending physicians in seven hospitals across three Canadian cities. Patients: Three hundred two individual rounds on 210 unique patients were observed. Interventions: Quantitative and qualitative data were collected using standardized observational tools. Measurements and Main Results: Among the 302 rounds observed, family attended in 68 rounds (23%), were present in ICU but did not attend in 59 rounds (20%), and were absent from the ICU in 175 rounds (58%). The median duration of rounds respectively for these three groups of patients was 20 minutes (interquartile range, 14–26 min), 16 minutes (interquartile range, 13–22 min), and 16 minutes (interquartile range, 10–23 min) (p = 0.01). There were no significant differences in prognostic discussions (35% vs 36% vs 36%; p = 0.99) or bedside teaching (35% vs 37% vs 34%; p = 0.88). The quality of rounds was not significantly associated with family attendance in rounds or presence in the ICU (quality score [1 (low) to 10 (high)] median 8 [interquartile range, 7–8] vs 7 [interquartile range, 6–9] vs 7 [interquartile range, 6–9]; p = 0.11). Qualitative analyses suggested that family attendance may influence relationship building, information gathering, patient and family education, team dynamics, future family meetings, workflow, and shared clinical decision-making. Conclusions: Our results suggest family attendance in ICU rounds is associated with longer duration of rounds, but not the frequency of trainee teaching, discussions of prognosis, or quality of rounds. Family attendance in rounds may enhance communication and complement family conferences. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by Strategic Clinical Network New Investigator Seed Fund, MSI Foundation. Dr. Bagshaw is supported by a Canada Research Chair in Critical Care Nephrology. Dr. Stelfox is supported by a Canadian Institutes of Health Research Embedded Clinician Researcher Award. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Selena.Au@AlbertaHealthServices.ca Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
https://ift.tt/2rv5aJ8
https://ift.tt/2rv5aJ8
Duration of Respiratory Failure After Trauma Is Not Associated With Increased Long-Term Mortality
https://ift.tt/2KaaA34
Niacin and Selenium Attenuate Brain Injury After Cardiac Arrest in Rats by Up-Regulating DJ-1-Akt Signaling
Objectives: To determine neuroprotective effects and mechanism of the combination therapy of niacin and selenium in cardiac arrest rats. Design: Prospective laboratory study. Setting: University laboratory. Subjects: Rat cortex neurons and male Sprague-Dawley rats (n = 68). Interventions: In rat cortex neurons underwent 90 minutes of oxygen-glucose deprivation and 22.5 hours of reoxygenation, effects of the combination therapy of niacin (0.9 mM) and selenium (1.5 μM) were investigated. The role of DJ-1 was determined using DJ-1 knockdown cells. In cardiac arrest rats, posttreatment effects of the combination therapy of niacin (360 mg/kg) and selenium (60 μg/kg) were evaluated. Measurements and Main Results: In oxygen-glucose deprivation and 22.5 hours of reoxygenation cells, combination therapy synergistically activated the glutathione redox cycle by a niacin-induced increase in glutathione reductase and a selenium-induced increase in glutathione peroxidase activities and reduced hydrogen peroxide level. It increased phosphorylated Akt and intranuclear Nuclear factor erythroid 2–related factor 2 expression and attenuated neuronal injury. However, these benefits were negated by DJ-1 knockdown. In cardiac arrest rats, combination therapy increased DJ-1, phosphorylated Akt, and intranuclear nuclear factor erythroid 2–related factor 2 expression, suppressed caspase 3 cleavage, and attenuated histologic injury in the brain tissues. It also improved the 7-day Neurologic Deficit Scales from 71.5 (66.0–74.0) to 77.0 (74.–80.0) (p = 0.02). Conclusions: The combination therapy of clinically relevant doses of niacin and selenium attenuated brain injury and improved neurologic outcome in cardiac arrest rats. Its benefits were associated with reactive oxygen species reduction and subsequent DJ-1-Akt signaling up-regulation. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare (grant number: HI12C1117). All authors have disclosed that this work was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare (grant number: HI12C1117). For information regarding this article, E-mail: suhgil@snu.ac.kr Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
https://ift.tt/2rx97Nm
https://ift.tt/2rx97Nm
Restoration of an academic historical gross pathology collection—refreshed impact on current medical teaching?
Abstract
The declaration of Leiden pronounces the demand to conserve pathological-anatomical collections as cultural heritage. Likewise, the Institute of Pathology of the Friedrich-Alexander-University Erlangen-Nuremberg owns macroscopic pathological-anatomical specimens reaching back over 150 years. The purpose of this work is to examine the impact, meaning, and perception of such historical preparations during the current medical curriculum. Additionally, the experiences from the renovation process can be used as a template for other institutes. All preparations were documented, photographed, and catalogued in an electronic database. During a restoration period, a series of didactically suitable specimens were professionally restored. Hereby, the help of a special course of interested students was admitted. In a second step, the specimens were integrated into the regular teaching of students in macroscopic pathology. An evaluation was carried out on two student cohorts with and without historical specimens by means of a questionnaire with 23 items and two free text fields. In total, 1261 specimens were registered covering diseases from almost the complete human body with a strong representation of the cardiovascular, urinary, gastrointestinal, and central nervous systems. Hereby, exceptional rare and untreated cases with medical relevance could be found and stepwise implemented into the curriculum. The student evaluation positively addressed that the courses became livelier and interactive. Furthermore, a more comprehensive overview and a better understanding of the macroscopic pathology were appreciated. However, more self-study time with the specimen was demanded. The authenticity of historical specimens contrasts with the tendency to carry out virtual "online" didactic methods. The stereoscopic view on often untreated and, therefore, unbiased cases enhances a skill-oriented deeper understanding of diseases. In conclusion, historical specimens regain interest and even didactic value, especially in an era of declining autopsy rates.
https://ift.tt/2wsa7XY
A Practical Guide to Conducting a Systematic Review and Meta-analysis of Health State Utility Values
Abstract
Economic analysts are increasingly likely to rely on systematic reviews and meta-analyses of health state utility values to inform the parameter inputs of decision-analytic modelling-based economic evaluations. Beyond the context of economic evaluation, evidence from systematic reviews and meta-analyses of health state utility values can be used to inform broader health policy decisions. This paper provides practical guidance on how to conduct a systematic review and meta-analysis of health state utility values. The paper outlines a number of stages in conducting a systematic review, including identifying the appropriate evidence, study selection, data extraction and presentation, and quality and relevance assessment. The paper outlines three broad approaches that can be used to synthesise multiple estimates of health utilities for a given health state or condition, namely fixed-effect meta-analysis, random-effects meta-analysis and mixed-effects meta-regression. Each approach is illustrated by a synthesis of utility values for a hypothetical decision problem, and software code is provided. The paper highlights a number of methodological issues pertinent to the conduct of meta-analysis or meta-regression. These include the importance of limiting synthesis to 'comparable' utility estimates, for example those derived using common utility measurement approaches and sources of valuation; the effects of reliance on limited or poorly reported published data from primary utility assessment studies; the use of aggregate outcomes within analyses; approaches to generating measures of uncertainty; handling of median utility values; challenges surrounding the disentanglement of utility estimates collected serially within the context of prospective observational studies or prospective randomised trials; challenges surrounding the disentanglement of intervention effects; and approaches to measuring model validity. Areas of methodological debate and avenues for future research are highlighted.
https://ift.tt/2G1697W
Trypanosoma cruzi Reactivation in the Brain
https://ift.tt/2I3BBbK
Moving On
Everyone in my examining room is aging on schedule, patients and doctor alike. It's quite a change from the scene a few decades ago, when all of us were young and the patients were dying, one HIV-fueled departure after another, each one surrounded by a little medical care to soothe the worst of it.…
https://ift.tt/2G41Ngq
Case 14-2018: A 68-Year-Old Woman with a Rash, Hyponatremia, and Uveitis
Presentation of Case. Dr. AbdulRasheed A. Alabi (Medicine): A 68-year-old woman was admitted to this hospital during the winter because of a rash, hyponatremia, and anterior uveitis. One month before admission, the patient traveled abroad. She spent a week in Sweden visiting family members,…
https://ift.tt/2jKlotn
Xanthoma Striatum Palmare
https://ift.tt/2ryfkaN
Idiopathic Pulmonary Fibrosis
The family of interstitial lung diseases is characterized by cellular proliferation, interstitial inflammation, fibrosis, or a combination of such findings within the alveolar wall that is not due to infection or cancer. Interstitial fibrosis is the predominant phenotype in most cases. The majority…
https://ift.tt/2G2387x
Essential Tremor
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations. A 62-year-old woman presents…
https://ift.tt/2I9Abs2
Seamless Genetic Conversion of SMN2 to SMN1 via CRISPR/Cpf1 and Single-Stranded Oligodeoxynucleotides in Spinal Muscular Atrophy Patient-Specific Induced Pluripotent Stem Cells
Human Gene Therapy, Ahead of Print.
https://ift.tt/2KPGtyZ
A Calsequestrin Cis-Regulatory Motif Coupled to a Cardiac Troponin T Promoter Improves Cardiac Adeno-Associated Virus Serotype 9 Transduction Specificity
Human Gene Therapy, Ahead of Print.
https://ift.tt/2rwQ0Cg
CRISPR/Cas9 Inhibits Multiple Steps of HIV-1 Infection
Human Gene Therapy, Ahead of Print.
https://ift.tt/2I52Qmj
Gene Therapy with Tetracycline-Regulated Human Recombinant COLIA1 cDNA Direct Adenoviral Delivery Enhances Fracture Healing in Osteoporotic Rats
Human Gene Therapy, Ahead of Print.
https://ift.tt/2ryagn7
Predicting responses to mechanical ventilation for preterm infants with acute respiratory illness using artificial neural networks
International Journal for Numerical Methods in Biomedical Engineering, EarlyView.
https://ift.tt/2I3ra84
Impact of Sleeping Altitude on Symptoms of Acute Mountain Sickness on Mt. Fuji
High Altitude Medicine &Biology, Ahead of Print.
https://ift.tt/2wrORl8
A comprehensive analysis of clinical trials including both immunotherapy and radiation therapy
Abstract
Purpose
Radiation therapy (RT) may work synergistically with cancer immunotherapies but clinical trial data is needed to validate this paradigm. We isolated the portfolio of trials that investigate the primary immunomodulatory properties of RT and examined recent trends in clinical trials that combine immunotherapy and RT (ITRT).
Methods
We queried clinicaltrials.gov for trials initiated since 2002 using both radiation and immunotherapy as mandated interventions. We designated the trials that examine the specific aspects of RT or its abscopal properties as "Primary RT Immunomodulation" trials. Chi-squared analysis determined differences between primary RT immunomodulation trials and those that incorporate RT as a secondary intervention. Joinpoint regression modeling determined the rate of change of the introduction of new trials over time.
Results
One hundred and ninety trials met inclusion criteria. Targeted immunostimulatory agents, including checkpoint inhibitors, were the most common immunotherapy (n = 79 [41.6%]). Sixty-six (34.7%) trials included RT as the primary intervention, with 50 (75.6%) of these utilizing stereotactic body radiation (SBRT). All ITRT trials increased at a rate of 14.8% per year. Primary RT immunomodulation trials increased at a rate of 26.8% per year. Primary RT immunomodulation trials were more likely to utilize targeted immunostimulatory agents (p < 0.01), and SBRT (p < 0.01), and more likely to involve metastatic sites (p < 0.01). The number of ITRT studies increased drastically in the latest two years of the study.
Conclusion
The number of new ITRT clinical trials is increasing rapidly. This increase in quantity may improve the clinical application of the immunomodulatory properties of RT.
https://ift.tt/2Ic8Y8l
Revisiting Blood Safety Practices Given Emerging Data about Zika Virus
New England Journal of Medicine, Volume 378, Issue 19, Page 1837-1841, May 2018.
https://ift.tt/2wsuggr
Idiopathic Pulmonary Fibrosis
New England Journal of Medicine, Volume 378, Issue 19, Page 1811-1823, May 2018.
https://ift.tt/2IwaRQM
Hemorrhagic Shock
New England Journal of Medicine, Volume 378, Issue 19, Page 1850-1853, May 2018.
https://ift.tt/2Iqge3M
Investigational Testing for Zika Virus among U.S. Blood Donors
New England Journal of Medicine, Volume 378, Issue 19, Page 1778-1788, May 2018.
https://ift.tt/2K84sbj
Venous Thromboembolism Prophylaxis after Hip or Knee Arthroplasty
New England Journal of Medicine, Volume 378, Issue 19, Page 1848-1849, May 2018.
https://ift.tt/2wvz84u
Maternal Sirolimus Therapy for Fetal Cardiac Rhabdomyomas
https://ift.tt/2IsSAni
Deployment of Preventive Interventions — Time for a Paradigm Shift
New England Journal of Medicine, Volume 378, Issue 19, Page 1761-1763, May 2018.
https://ift.tt/2IrPTm2
MRI-Targeted versus Ultrasonography-Guided Biopsy for Suspected Prostate Cancer
New England Journal of Medicine, Volume 378, Issue 19, Page 1835-1836, May 2018.
https://ift.tt/2IrPYWS
Trypanosoma cruzi Reactivation in the Brain
https://ift.tt/2K84obz
Essential Tremor
New England Journal of Medicine, Volume 378, Issue 19, Page 1802-1810, May 2018.
https://ift.tt/2K92kjA
Firearm Injuries and NRA Annual Conventions
New England Journal of Medicine, Volume 378, Issue 19, Page 1853-1853, May 2018.
https://ift.tt/2IoQGE6
Intravenous Immune Globulin to Prevent Heparin-Induced Thrombocytopenia
https://ift.tt/2K9nIW8
Thrombectomy for Stroke with Selection by Perfusion Imaging
New England Journal of Medicine, Volume 378, Issue 19, Page 1849-1850, May 2018.
https://ift.tt/2IrPVua
Case 14-2018: A 68-Year-Old Woman with a Rash, Hyponatremia, and Uveitis
New England Journal of Medicine, Volume 378, Issue 19, Page 1825-1833, May 2018.
https://ift.tt/2K7IDst
Moving On
New England Journal of Medicine, Volume 378, Issue 19, Page 1763-1765, May 2018.
https://ift.tt/2ImDGPx
Tackling Tumors with Small RNAs Derived from Transfer RNA
New England Journal of Medicine, Volume 378, Issue 19, Page 1842-1843, May 2018.
https://ift.tt/2IsnHzi
The 2017 Nobel Peace Prize and the Doomsday Clock — The End of Nuclear Weapons or the End of Us?
https://ift.tt/2wpG4jK
Cancers, Vol. 10, Pages 141: Role of the Bone Microenvironment in the Development of Painful Complications of Skeletal Metastases
Cancers, Vol. 10, Pages 141: Role of the Bone Microenvironment in the Development of Painful Complications of Skeletal Metastases
Cancers doi: 10.3390/cancers10050141
Authors: Sun H. Park Matthew R. Eber D. Brooke Widner Yusuke Shiozawa
Cancer-induced bone pain (CIBP) is the most common and painful complication in patients with bone metastases. It causes a significant reduction in patient quality of life. Available analgesic treatments for CIBP, such as opioids that target the central nervous system, come with severe side effects as well as the risk of abuse and addiction. Therefore, alternative treatments for CIBP are desperately needed. Although the exact mechanisms of CIBP have not been fully elucidated, recent studies using preclinical models have demonstrated the role of the bone marrow microenvironment (e.g., osteoclasts, osteoblasts, macrophages, mast cells, mesenchymal stem cells, and fibroblasts) in CIBP development. Several clinical trials have been performed based on these findings. CIBP is a complex and challenging condition that currently has no standard effective treatments other than opioids. Further studies are clearly warranted to better understand this painful condition and develop more effective and safer targeted therapies.
https://ift.tt/2jKOicX
Genomic Prediction Accounting for Genotype by Environment Interaction Offers an Effective Framework for Breeding Simultaneously for Adaptation to an Abiotic Stress and Performance Under Normal Cropping Conditions in Rice
Developing rice varieties adapted to alternate wetting and drying water management is crucial for the sustainability of irrigated rice cropping systems. Here we report the first study exploring the feasibility of breeding rice for adaptation to alternate wetting and drying using genomic prediction methods that account for genotype by environment interactions. Two breeding populations (a reference panel of 284 accessions and a progeny population of 97 advanced lines) were evaluated under alternate wetting and drying and continuous flooding management systems. The predictive ability of genomic prediction for response variables (index of relative performance and the slope of the joint regression) and for multi-environment genomic prediction models were compared. For the three traits considered (days to flowering, panicle weight and nitrogen-balance index), significant genotype by environment interactions were observed in both populations. In cross validation, predictive ability for the index was on average lower (0.31) than that of the slope of the joint regression (0.64) whatever the trait considered. Similar results were found for progeny validation. Both cross-validation and progeny validation experiments showed that the performance of multi-environment models predicting unobserved phenotypes of untested entrees was similar to the performance of single environment models with differences in predictive ability ranging from -6% to 4% depending on the trait and on the statistical model concerned. The predictive ability of multi-environment models predicting unobserved phenotypes of entrees evaluated under both water management systems outperformed single environment models by an average of 30%. Practical implications for breeding rice for adaptation to alternate wetting and drying system are discussed.
https://ift.tt/2jOWUix
From human antibody structure and function towards the design of a novel Plasmodium falciparum circumsporozoite protein malaria vaccine
Hedda Wardemann | Rajagopal Murugan
https://ift.tt/2K6CU6m
Sustainable vaccine development: a vaccine manufacturer's perspective
Rino Rappuoli | Emmanuel Hanon
https://ift.tt/2wsQDCj
Sociodemographic variation in the use of chemotherapy and radiotherapy in patients with stage IV lung, oesophageal, stomach and pancreatic cancer: evidence from population-based data in England during 2013–2014
Sociodemographic variation in the use of chemotherapy and radiotherapy in patients with stage IV lung, oesophageal, stomach and pancreatic cancer: evidence from population-based data in England during 2013–2014
Sociodemographic variation in the use of chemotherapy and radiotherapy in patients with stage IV lung, oesophageal, stomach and pancreatic cancer: evidence from population-based data in England during 2013–2014, Published online: 10 May 2018; doi:10.1038/s41416-018-0028-7
Sociodemographic variation in the use of chemotherapy and radiotherapy in patients with stage IV lung, oesophageal, stomach and pancreatic cancer: evidence from population-based data in England during 2013–2014
https://ift.tt/2I6x8Fr
When it comes to genomic analysis of tumours, don't buy in bulk
When it comes to genomic analysis of tumours, don't buy in bulk
When it comes to genomic analysis of tumours, don't buy in bulk, Published online: 10 May 2018; doi:10.1038/s41416-018-0096-8
When it comes to genomic analysis of tumours, don't buy in bulk
https://ift.tt/2ruK1P4
FDA's Approval of the First Biosimilar to Bevacizumab
Passage of the Biologics Price Competition and Innovation Act of 2009 created an abbreviated licensure pathway for biosimilar products. The Food and Drug Administration approved ABP215 (MVASI, bevacizumab-awwb, Amgen) as a biosimilar to US-licensed Avastin (bevacizumab, Genentech) based on an extensive comparative analytical characterization, data obtained in a pharmacokinetic similarity study in healthy subjects, and a comparative clinical study in patients with non-small cell lung cancer. The totality of the evidence for biosimilarity supported extrapolation of the data to support licensure as a biosimilar for other approved indications of US-licensed Avastin, without the need of additional clinical studies.
https://ift.tt/2rz2E3u
PTPN12/PTP-PEST Regulates Phosphorylation-Dependent Ubiquitination and Stability of Focal Adhesion Substrates in Invasive Glioblastoma Cells
Glioblastoma (GBM) is an invasive brain cancer with tumor cells that disperse from the primary mass, escaping surgical resection and invariably giving rise to lethal recurrent lesions. Here we report that PTP-PEST, a cytoplasmic protein tyrosine phosphatase, controls GBM cell invasion by physically bridging the focal adhesion protein Crk-associated substrate (Cas) to valosin containing protein (Vcp), an ATP-dependent protein segregase that selectively extracts ubiquitinated proteins from multiprotein complexes and targets them for degradation via the ubiquitin proteasome system. Both Cas and Vcp are substrates for PTP-PEST, with the phosphorylation status of tyrosine 805 (Y805) in Vcp impacting affinity for Cas in focal adhesions and controlling ubiquitination levels and protein stability. Perturbing PTP-PEST-mediated phosphorylation of Cas and Vcp led to alterations in GBM cell invasive growth in vitro and in pre-clinical mouse models. Collectively, these data reveal a novel regulatory mechanism involving PTP-PEST, Vcp, and Cas that dynamically balances phosphorylation-dependent ubiquitination of key focal proteins involved in GBM cell invasion.
https://ift.tt/2IaEYd5
Correction to: 3L, 5L, What the L? A NICE Conundrum
The article 3L, 5L, What the L? A NICE Conundrum Written by Nancy Devlin, John Brazier, A. Simon Pickard, Elly Stolk was originally published electronically on the publisher's internet portal (currently Springer Link) on (26th February, 2018) without open access.
https://ift.tt/2KNPbhj
Calcifying Odontogenic Cyst with Extensive Areas of Dentinoid: Uncommon Case Report and Update of Main Findings
The calcifying odontogenic cyst (COC) is a benign odontogenic cyst that occurs in the gnathic bones. This cyst is part of a spectrum of lesions characterized by odontogenic epithelium containing "ghost cells," which may undergo calcification. Areas of an eosinophilic matrix material compatible dentinoid also may present adjacent to the epithelial component. However, these areas of dentinoid commonly do not appear so abundant in COCs. In this study, we report a case of intraosseous COC with extensive areas of dentinoid and perform an update regarding the clinical, radiographical, histopathological, and differential diagnosis, treatment, and prognosis of this cystic lesion.
https://ift.tt/2rwC4ZT
Cost Savings Limited With Generic Imatinib
WEDNESDAY, May 9, 2018 -- Prices of imatinib (Gleevec) remained high even after a generic version was introduced, according to a study published in the May issue of Health Affairs. Ashley L. Cole, from the University of North Carolina at Chapel...
https://ift.tt/2KNFS0R
Low Procedure Volume for Many Surgeons Doing Hysterectomies
WEDNESDAY, May 9, 2018 -- A substantial number of surgeons performing hysterectomies have low procedural volumes, according to a study published online May 9 in Obstetrics & Gynecology. Maria P. Ruiz, D.O., from Columbia University in New York...
https://ift.tt/2G2cS1y
Lymphoma, Leukemia Survivors Have Increased Health Care Use
WEDNESDAY, May 9, 2018 -- Survivors of lymphoma and chronic lymphocytic leukemia (CLL) have increased use of health care services versus a normative population, according to a study published online April 26 in Cancer. Lindy P.J. Arts, from the...
https://ift.tt/2jJuXsB
Birth Factors Mostly Explain England's Child Mortality Rate
WEDNESDAY, May 9, 2018 -- Birth characteristics largely explain the higher child mortality in England versus Sweden, according to a study published online May 3 in The Lancet. Ania Zylbersztejn, Ph.D., from the Farr Institute of Health Informatics...
https://ift.tt/2G0s0N7
Depressive Symptoms Tied to Memory, Aging of the Brain
WEDNESDAY, May 9, 2018 -- Greater depressive symptoms are associated with episodic memory and markers of brain aging in older Caribbean Hispanic patients, according to a study published online May 9 in Neurology. Adina Zeki Al Hazzouri, Ph.D., from...
https://ift.tt/2KOJ5Nq
Effect of Transmural Differences in Excitation-Contraction Delay and Contraction Velocity on Left Ventricle Isovolumic Contraction: A Simulation Study
Recent studies have shown that left ventricle (LV) exhibits considerable transmural differences in active mechanical properties induced by transmural differences in electrical activity, excitation-contraction coupling, and contractile properties of individual myocytes. It was shown that the time between electrical and mechanical activation of myocytes (electromechanical delay: EMD) decreases from subendocardium to subepicardium and, on the contrary, the myocyte shortening velocity (MSV) increases in the same direction. To investigate the physiological importance of this inhomogeneity, we developed a new finite element model of LV incorporating the observed transmural gradients in EMD and MSV. Comparative simulations with the model showed that when EMD or MSV or both were set constant across the LV wall, the LV contractility during isovolumic contraction (IVC) decreased significantly ( was reduced by 2 to 38% and IVC was prolonged by 18 to 73%). This was accompanied by an increase of transmural differences in wall stress. These results suggest that the transmural differences in EMD and MSV play an important role in physiological contractility of LV by synchronising the contraction of individual layers of ventricular wall during the systole. Reduction or enhancement of these differences may therefore impair the function of LV and contribute to heart failure.
https://ift.tt/2jKSSaZ
Screening for gastric cancer with magnetically controlled capsule gastroscopy in asymptomatic individuals
Gastric cancer (GC) is the fourth most common cancer and the fourth leading cause of cancer death worldwide. In some Asian countries, screening esophagogastroduodenoscopy (EGD) has greatly improved the survival rate. However, patients' discomfort and the need for sedation may limit adherence to screening programs. Prior studies have shown good tolerance and good agreement of magnetically controlled capsule gastroscopy (MCCG) with EGD. This study was designed to assess the application of MCCG in GC detection in an asymptomatic population.
https://ift.tt/2I4tLyI
Inspection of endoscope instrument channels after reprocessing using a prototype borescope
Visual inspection of the instrument channel has been proposed as a quality assurance step during endoscope reprocessing. However, the nature and severity of findings in a broad array of endoscopes (gastroscopes, colonoscopes, duodenoscopes, and echoendoscopes) after systemic implementation of an inspection protocol remain unknown. In addition, a study using borescope inspection in upper endoscopes and colonoscopes raised concerns about persistent simethicone residue despite full reprocessing.
https://ift.tt/2ryxzwL
Outcomes of endoscopic resection for superficial duodenal epithelial neoplasia
Pancreaticoduodenectomy is an invasive procedure, and endoscopic resection (ER) is an alternative therapy. However, details regarding the outcomes of ER are unknown, especially for superficial duodenal epithelial neoplasia (SDET). The aim of this study was to elucidate the outcomes of ER for SDET and to compare endoscopic mucosal resection (EMR) with endoscopic submucosal dissection (ESD).
https://ift.tt/2KOyYZ5
It’s not what you think: Associations between perceived cognitive and physical status and prognostic understanding in patients with advanced cancer
Patients with advanced cancer often overestimate their time left to live. Those who have heightened awareness of their cognitive and physical deficits at the end of life may have a better prognostic understanding.
https://ift.tt/2IbHP5r
Validation of the Dyspnea Exertion Scale of Breathlessness in people with life-limiting illness
Although chronic breathlessness is common in life-limiting illnesses, validated, feasible instruments to measure functional impact of the symptom in this population are scarce. We aimed to validate the Dyspnea Exertion Scale (DES) compared with the modified Medical Research Council (mMRC) breathlessness scale for test-retest reliability, concurrent validity and responsiveness in people with life-limiting illness.
https://ift.tt/2I0TZ4W
Quality of Life, Symptoms, and Self-Management Strategies After Gastroesophageal Cancer Surgery
The most common and effective treatment strategy for gastroesophageal cancer is surgery. Surgical procedures (esophagectomy, gastrectomy) are invasive and complex, and risk for postoperative complications is high (up to 40%).1 Postoperative recovery is slow, with impairments in quality of life (QOL) that can persist ten years after surgery.2 Nutritional symptoms are common (nausea, vomiting, early satiety, diarrhea, pain), and often result in severe malnutrition.3 These symptoms and associated eating problems are often a major source of anxiety for patients postoperatively.
https://ift.tt/2I7f2yU
Validation of the Amharic Version of the Brief Fatigue Inventory (BFI-Am) for Assessment of Cancer Related Fatigue in Ethiopian Cancer Patients
Even though cancer related fatigue (CRF) is a highly prevalent and distressing symptom associated with cancer and its treatment; it is mostly under-screened, under-assessed and under-treated. The Brief Fatigue Inventory (BFI) is a reliable and valid instrument to assess CRF.
https://ift.tt/2jJPixS
Effects of Virologic Response to Treatment on Short- and Long-term Outcomes of Patients With Chronic HBV Infection and Decompensated Cirrhosis
Little is known about the effects of antiviral therapy on short- and long-term survival of patients with hepatitis B virus (HBV)-related decompensated cirrhosis. We aimed to determine whether a maintained virologic response (MVR, defined as persistent undetectable HBV DNA during therapy) associates with short-term (6-month) and long-term (6–120 months) survival of patients with decompensated cirrhosis.
https://ift.tt/2I9YfuU
Criteria to Determine Reliability of Non-invasive Assessment of Liver Fibrosis With Virtual Touch Quantification
Virtual Touch Quantification (VTQ) evaluates liver fibrosis in patients with chronic liver diseases by measuring shear wave speed in the liver. We aimed to determine the reliability criteria of VTQ examination.
https://ift.tt/2I6oyWQ
Level of hepatitis B (HB) core antibody associates with seroclearance of HBV DNA and HB surface antigen in HB e antigen-seronegative patients
Although a low level of hepatitis B surface antigen (HBsAg) is a marker of hepatitis B virus (HBV) seroclearance, additional biomarkers are needed for more accurate prediction. We investigated whether quantification of antibody against HBV core protein (anti-HBc) can identify patients with undetectable levels of HBV DNA and HBsAg seroclearance among those who were HBV e antigen (HBeAg)-seronegative.
https://ift.tt/2jPnRTD
Widefield High Frame Rate Single-Photon SPAD Imagers for SPIM-FCS
Photon-counting sensors based on standard complementary metal-oxide-semiconductor single-photon avalanche diodes (SPADs) represent an emerging class of imagers that enable the counting and/or timing of single photons at zero readout noise (better than high-speed electron-multiplying charge-coupling devices) and over large arrays. They have seen substantial progress over the last 15 years, increasing their spatial resolution, timing accuracy, and sensitivity while reducing spurious signals such as afterpulsing and dark counts.
https://ift.tt/2G1eCIo
GADD45α sensitizes cervical cancer cells to radiotherapy via increasing cytoplasmic APE1 level
GADD45α sensitizes cervical cancer cells to radiotherapy via increasing cytoplasmic APE1 level
GADD45α sensitizes cervical cancer cells to radiotherapy via increasing cytoplasmic APE1 level, Published online: 09 May 2018; doi:10.1038/s41419-018-0452-x
GADD45α sensitizes cervical cancer cells to radiotherapy via increasing cytoplasmic APE1 levelhttps://ift.tt/2wsnTty
iASPP–PP1 complex is required for cytokinetic abscission by controlling CEP55 dephosphorylation
iASPP–PP1 complex is required for cytokinetic abscission by controlling CEP55 dephosphorylation
iASPP–PP1 complex is required for cytokinetic abscission by controlling CEP55 dephosphorylation, Published online: 09 May 2018; doi:10.1038/s41419-018-0561-6
iASPP–PP1 complex is required for cytokinetic abscission by controlling CEP55 dephosphorylationhttps://ift.tt/2rvNn4d
Inhibitor of apoptosis proteins are required for effective fusion of autophagosomes with lysosomes
Inhibitor of apoptosis proteins are required for effective fusion of autophagosomes with lysosomes
Inhibitor of apoptosis proteins are required for effective fusion of autophagosomes with lysosomes, Published online: 09 May 2018; doi:10.1038/s41419-018-0508-y
Inhibitor of apoptosis proteins are required for effective fusion of autophagosomes with lysosomeshttps://ift.tt/2K84qR3
miR-338-3p functions as a tumor suppressor in gastric cancer by targeting PTP1B
miR-338-3p functions as a tumor suppressor in gastric cancer by targeting PTP1B
miR-338-3p functions as a tumor suppressor in gastric cancer by targeting PTP1B, Published online: 09 May 2018; doi:10.1038/s41419-018-0611-0
miR-338-3p functions as a tumor suppressor in gastric cancer by targeting PTP1Bhttps://ift.tt/2KaDfVN
E2F1 inhibition mediates cell death of metastatic melanoma
E2F1 inhibition mediates cell death of metastatic melanoma
E2F1 inhibition mediates cell death of metastatic melanoma, Published online: 09 May 2018; doi:10.1038/s41419-018-0566-1
E2F1 inhibition mediates cell death of metastatic melanomahttps://ift.tt/2I58Jjt
Leukaemic alterations of IKZF1 prime stemness and malignancy programs in human lymphocytes
Leukaemic alterations of IKZF1 prime stemness and malignancy programs in human lymphocytes
Leukaemic alterations of <i>IKZF1</i> prime stemness and malignancy programs in human lymphocytes, Published online: 09 May 2018; doi:10.1038/s41419-018-0600-3
Leukaemic alterations of IKZF1 prime stemness and malignancy programs in human lymphocyteshttps://ift.tt/2wtVwvb
p53-dependent CD51 expression contributes to characteristics of cancer stem cells in prostate cancer
p53-dependent CD51 expression contributes to characteristics of cancer stem cells in prostate cancer
p53-dependent CD51 expression contributes to characteristics of cancer stem cells in prostate cancer, Published online: 09 May 2018; doi:10.1038/s41419-018-0541-x
p53-dependent CD51 expression contributes to characteristics of cancer stem cells in prostate cancerhttps://ift.tt/2IpTsci
Grail is involved in adipocyte differentiation and diet-induced obesity
Grail is involved in adipocyte differentiation and diet-induced obesity
Grail is involved in adipocyte differentiation and diet-induced obesity, Published online: 09 May 2018; doi:10.1038/s41419-018-0596-8
Grail is involved in adipocyte differentiation and diet-induced obesityhttps://ift.tt/2K6i7Qm
The implications of TrkA and MET aberrations in de novo salivary duct carcinoma
Salivary duct carcinoma (SDC) is an aggressive carcinoma with poor prognosis. Although anti-HER2 therapy is a potential treatment option for HER2-positive SDC, other potential therapeutic targets are not known, in particular for HER2-negative cases. In this study, the recently identified receptor tyrosine kinases MET and tropomyosin-receptor kinase (Trk) were investigated as potential therapeutic targets. A total of 28 consecutive, surgically resected, de novo SDC cases were selected after evaluating histology and immunohistochemical expression of androgen receptor.
https://ift.tt/2I54F2q
Evaluating agreement, histological features and relevance of separating pleomorphic and florid lobular carcinoma-in-situ subtypes
Morphological variants of lobular carcinoma in situ (LCIS) include classical- (CLCIS), pleomorphic- (PLCIS) and florid-type (FLCIS). Treatment guidelines suggest managing PLCIS and FLCIS like ductal carcinoma in situ (DCIS); therefore accurate identification of LCIS subtypes is critical. However significance of separating PLCIS from FLCIS is not clear. Also inter-observer agreement in identifying LCIS subtypes, using contemporary criteria, is not known. We aimed to evaluate inter-observer agreement amongst breast pathologists in diagnosing LCIS subtypes and use the agreement data to justify LCIS classification for management purposes.
https://ift.tt/2I8q3Qr
Overexpression of MCM6 predicts poor survival in patients with glioma
Minichromosome maintenance proteins (MCMs) play an essential role in DNA replication and other cellular activities. However, their expression levels and clinical value in glioma are unclear. In the present study, we analyzed the relationship between MCM mRNA expression and clinical parameters in 325 gliomas, and found that MCM6 presented high expression and was associated with poor survival. Immunohistochemistry analysis of an independent dataset of 423 glioma tissues confirmed the overexpression of MCM6 protein, especially in glioblastomas (GBMs) with shorter overall survival (OS).
https://ift.tt/2I3Er0z
Determination of the mutational landscape in Taiwanese patients with papillary thyroid cancer by whole-exome sequencing
Among women in Taiwan, thyroid cancer is the fifth most common malignant neoplasia. However, genomic profiling of papillary thyroid cancer (PTC) cases from Taiwan has not been attempted previously. We used whole-exome sequencing to identify mutations in a cohort of 19 PTC patients. Sequencing was performed using the Illumina system; Sanger sequencing was used to validate all identified mutations. We identified new somatic mutations in APC, DICER1, LRRC8D and NDRG1. We also found somatic mutations in ARID5A, CREB3L2, MDM4, PPP2R5A and TFPT; mutations in these genes had been found previously in other tumors, but had not been described previously in PTC.
https://ift.tt/2I7bblb
Children with Chronic Disease Bear the Highest Burden of Pediatric Sepsis
To describe the contemporary epidemiology of pediatric sepsis in children with chronic disease, and the contribution of chronic diseases to mortality. We examined the incidence and hospital mortality of pediatric sepsis in a nationally representative sample and described the contribution of chronic diseases to hospital mortality.
https://ift.tt/2rCROd5
24-Hour Ambulatory Blood Pressure after Adenotonsillectomy in Childhood Sleep Apnea
To assess the effects of adenotonsillectomy (T&A) on ambulatory blood pressure (ABP) in childhood obstructive sleep apnea (OSA).
https://ift.tt/2rx2oCe
Real-World Implementation of Infant Behavioral Sleep Interventions: Results of a Parental Survey
To describe parental practices implementing behavioral sleep intervention (BSI) outside a clinical setting.
https://ift.tt/2I3vnJ5
Increased Fracture Risk with Furosemide Use in Children with Congenital Heart Disease
To determine the association of furosemide therapy with the incidence of bone fractures in children with congenital heart disease.
https://ift.tt/2I2SD9T
Sildenafil and Retinopathy of Prematurity in Preterm Infants with Bronchopulmonary Dysplasia
To assess whether sildenafil is associated with worsening retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants (≤1500 g) with bronchopulmonary dysplasia (BPD).
https://ift.tt/2rx2rho
Psychosocial Characteristics of Women with a Delayed Diagnosis of Turner Syndrome
To characterize the psychosocial profiles of adult women diagnosed with Turner syndrome before (early diagnosis) and at or after (late diagnosis) 13 years of age.
https://ift.tt/2I5eAoM
Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease
To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis.
https://ift.tt/2I2OHpQ
Neonatal Hyperglycemia—Causes, Treatments, and Cautions
In this volume of The Journal, Zamir et al report persistence of hyperglycemia for a surprisingly long period after birth, up to at least 28 days, in a relatively large number (580) of extremely preterm infants born at <27 weeks gestation.1 Hyperglycemia was defined as >180 mg/dL (>10 mmol/L), a value considerably higher than most text book definitions of neonatal hyperglycemia (commonly >125 mg/dL [~7 mmol/L]) and much above the upper limit found in normal human fetuses over the second half of gestation (108 mg/dL [6 mmol/L]).
https://ift.tt/2rCRWcz
Fabius Anesthesia Machines by Dräger Medical: Class I Recalls - Due to Production Step Error
[Posted 05/09/2018] AUDIENCE: Anesthesiology, Risk Manager, Surgery ISSUE: Dräger Medical is recalling the Fabius Anesthesia machines due to excessive oil that was not removed at the time of production. Such excess oil may interfere with the...
https://ift.tt/2IomkBE
Microbial diversity and ecotoxicity of sediments 3 years after the Jiaozhou Bay oil spill
In 2013, the "Qingdao oil pipeline explosion" released an estimated 2000 tons of oil into the environment. Sediment samples were collected from ten sites in Jiaozhou Bay and Shilaoren Beach to evaluate the inf...
https://ift.tt/2rtWnXS
Stepwise partially overlapping primer-based PCR for genome walking
A stepwise partially overlapping primer-based PCR (SWPOP-PCR) method for isolating flanking unknown DNA regions was developed, which comprises three rounds of nested PCRs sequentially driven by SWPOP primer-ne...
https://ift.tt/2wn54Ia
Fabius Anesthesia Machines by Dräger Medical: Class I Recalls - Due to Production Step Error
[Posted 05/09/2018] AUDIENCE: Anesthesiology, Risk Manager, Surgery ISSUE: Dräger Medical is recalling the Fabius Anesthesia machines due to excessive oil that was not removed at the time of production. Such excess oil may interfere with the...
https://ift.tt/2IomkBE
Application of the Canadian Computed Tomography Head Rule to Patients With Minimal Head Injury
Two clinical decision rules, the Canadian CT Head Rule and the New Orleans Criteria, set the standard to guide clinicians in determining which patients with minor head trauma need computed tomography (CT) imaging. Both rules were derived with patients with minor head injury who had had a loss of consciousness or witnessed disorientation. No evidence exists for evaluating patients and need for CT imaging with minimal head injury; that is, patients who had a head injury but no loss of consciousness or disorientation and therefore would have been excluded from the Canadian CT Head Rule and New Orleans Criteria trials.
https://ift.tt/2IoFxTX
Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock: Rationale for a Randomized Trial
Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg [4 to 6 L in an 80-kg adult] during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg [≤2 to 3 L]), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion.
https://ift.tt/2wy2fnY
In Patients With Acute Myocardial Infarction and No Hypoxemia, Does Oxygen Therapy Improve Outcomes Compared With No Supplemental Oxygen?
Authors included 7 randomized controlled trials with 3,842 patients receiving oxygen therapy and 3,860 patients not receiving supplemental oxygen. Time frames for outcome measurements ranged from index admission up to 12 months. Most included patients were men, and the most common comorbidities were hypertension, hyperlipidemia, diabetes, and smoking. Overall, there was no association between oxygen supplementation with any benefit in patients with acute myocardial infarction (Table). Six studies reported all-cause mortality, 6 reported recurrent ischemia or myocardial infarction, 3 reported heart failure, and 5 reported arrhythmia.
https://ift.tt/2IumZSe
Emergency Department Implementation of the Centers for Disease Control and Prevention Pediatric Mild Traumatic Brain Injury Guideline Recommendations
From 2005 to 2009, children made more than 2 million outpatient visits and almost 3 million emergency department (ED) visits for mild traumatic brain injury.1 The actual number of mild traumatic brain injury cases is difficult to assess because patients may seek treatment in a variety of medical or school settings, or not at all. However, there is evidence that these numbers are increasing; in 2007, there were 461,000 ED visits for traumatic brain injury among children aged 14 years and younger; by 2013, that number had increased to 642,000.
https://ift.tt/2wy277Y
State of the National Emergency Department Workforce: Who Provides Care Where?
We describe the current US emergency medicine workforce in terms of clinician type and examine rural and urban emergency medicine workforce differences.
https://ift.tt/2wupjUs
Construction of an Improved Multi-Tetrode Hyperdrive for Large-Scale Neural Recording in Behaving Rats
https://ift.tt/2K4guCH
Photoselective Vaporesection of the Prostate via an End-firing Lithium Triborate Crystal Laser
https://ift.tt/2jIWfiE
Lesbian, Bi Women More Likely to Develop T2DM at Younger Age
WEDNESDAY, May 9, 2018 -- Lesbian and bisexual (LB) women are more likely to develop type 2 diabetes at a younger age than heterosexual women, with the difference mediated by body mass index (BMI), according to a study published online May 2 in...
https://ift.tt/2rx9RBn
Coaching to Up H2O Intake Does Not Slow eGFR Decline in CKD
WEDNESDAY, May 9, 2018 -- Coaching to increase water intake does not significantly slow the decline in kidney function among adults with chronic kidney disease, according to a study published in the May 8 issue of the Journal of the American Medical...
https://ift.tt/2KNOd4o
Marijuana Use Not Linked to Risk of Arrhythmias After Acute MI
WEDNESDAY, May 9, 2018 -- For patients with acute myocardial infarction (AMI), marijuana use is not associated with increased risk of ventricular tachycardia/ventricular fibrillation (VT/VF) or cardiac arrest, according to a study presented at the...
https://ift.tt/2rx9Opb
Surgery for Hip Fx Cuts Mortality in NH Residents With Dementia
WEDNESDAY, May 9, 2018 -- For nursing home (NH) residents with dementia and hip fracture, surgical hip fracture repair is associated with lower mortality, according to a study published online May 7 in JAMA Internal Medicine. Sarah D. Berry, M.D.,...
https://ift.tt/2I2noM9
At Low Temps, Air Pollution May Up Risk of Sudden Cardiac Death
WEDNESDAY, May 9, 2018 -- Exposure to particulate matter less than 2.5 µm in diameter (PM2.5) is associated with increased risk of sudden cardiac death (SCD) at low temperatures in women, according to a study presented at the annual meeting of the...
https://ift.tt/2rx85jE
Peds Fasting Duration Not Tied to Adverse Sedation Outcomes
WEDNESDAY, May 9, 2018 -- For children undergoing procedural sedation for a painful procedure, fasting duration is not associated with adverse events, according to a study published online May 7 in JAMA Pediatrics. Maala Bhatt, M.D., from the...
https://ift.tt/2I2qP5A
Chronic Aspirin Exposure Linked to Melanoma Risk in Males
WEDNESDAY, May 9, 2018 -- Chronic acetylsalicylic acid (ASA; aspirin) exposure is associated with increased risk of malignant melanoma (MM) in men, but not women, according to a letter to the editor published online March 27 in the Journal of the...
https://ift.tt/2rx9KWt
Women Have Stronger Link Between APOE-ε4, CSF Tau Levels
WEDNESDAY, May 9, 2018 -- The correlation between the apolipoprotein E (APOE) gene allele APOE-ε4 and cerebrospinal fluid (CSF) tau levels is stronger among women than men, according to a study published online May 7 in JAMA Neurology. Timothy J....
https://ift.tt/2I0M3R7
Crowdfunding Exaggerates Efficacy of Unproven Stem Cell Tx
WEDNESDAY, May 9, 2018 -- Crowdfunding campaigns for unproven stem cell-based interventions tend to exaggerate the efficacy and underemphasize the risks, according to a research letter published in the May 8 issue of the Journal of the American...
https://ift.tt/2rwh98s
Psychological Therapies May Help Older Adults With Chronic Pain
WEDNESDAY, May 9, 2018 -- For older adults with chronic pain, psychological interventions have small benefits, including reducing pain and catastrophizing beliefs, according to a review published online May 7 in JAMA Internal Medicine. Bahar...
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NPY Induces Stress Resilience via Downregulation of Ih in Principal Neurons of Rat Basolateral Amygdala
Neuropeptide Y (NPY) expression is tightly linked with the development of stress resilience in rodents and humans. Local NPY injections targeting the basolateral amygdala (BLA) produce long-term behavioral stress resilience in male rats via an unknown mechanism. Previously, we showed that activation of NPY Y1 receptors hyperpolarizes BLA principal neurons (PNs) through inhibition of the hyperpolarization-activated, depolarizing H-current, Ih. The present studies tested whether NPY treatment induces stress resilience by modulating Ih. NPY (10 pmol) was delivered daily for 5 d bilaterally into the BLA to induce resilience; thereafter, the electrophysiological properties of PNs and the expression of Ih in the BLA were characterized. As reported previously, increases in social interaction (SI) times persisted weeks after completion of NPY administration. In vitro intracellular recordings showed that repeated intra-BLA NPY injections resulted in hyperpolarization of BLA PNs at 2 weeks (2W) and 4 weeks (4W) after NPY treatment. At 2W, spontaneous IPSC frequencies were increased, whereas at 4W, resting Ih was markedly reduced and accompanied by decreased levels of HCN1 mRNA and protein expression in BLA. Knock-down of HCN1 channels in the BLA with targeted delivery of lentivirus containing HCN1-shRNA increased SI beginning 2W after injection and induced stress resilience. NPY treatment induced sequential, complementary changes in the inputs to BLA PNs and their postsynaptic properties that reduce excitability, a mechanism that contributes to less anxious behavior. Furthermore, HCN1 knock-down mimicked the increases in SI and stress resilience observed with NPY, indicating the importance of Ih in stress-related behavior.
SIGNIFICANCE STATEMENT Resilience improves mental health outcomes in response to adverse situations. Neuropeptide Y (NPY) is associated with decreased stress responses and the expression of resilience in rodents and humans. Single or repeated injections of NPY into the basolateral amygdala (BLA) buffer negative behavioral effects of stress and induce resilience in rats, respectively. Here, we demonstrate that repeated administration of NPY into the BLA unfolds several cellular mechanisms that decrease the activity of pyramidal output neurons. One key mechanism is a reduction in levels of the excitatory ion channel HCN1. Moreover, shRNA knock-down of HCN1 expression in BLA recapitulates some of the actions of NPY and causes potent resilience to stress, indicating that this channel may be a possible target for therapy.
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Neural Activity in Ventral Medial Prefrontal Cortex Is Modulated More Before Approach Than Avoidance During Reinforced and Extinction Trial Blocks
Ventromedial prefrontal cortex (vmPFC) is thought to provide regulatory control over Pavlovian fear responses and has recently been implicated in appetitive approach behavior, but much less is known about its role in contexts in which appetitive and aversive outcomes can be obtained and avoided, respectively. To address this issue, we recorded from single neurons in vmPFC while male rats performed our combined approach and avoidance task under reinforced and non-reinforced (extinction) conditions. Surprisingly, we found that cues predicting reward modulated cell firing in vmPFC more often and more robustly than cues preceding avoidable shock; in addition, firing of vmPFC neurons was both response (press or no-press) and outcome (reinforced or extinction) selective. These results suggest a complex role for vmPFC in regulating behavior and support its role in appetitive contexts during both reinforced and non-reinforced conditions.
SIGNIFICANCE STATEMENT Selecting context-appropriate behaviors to gain reward or avoid punishment is critical for survival. Although the role of ventromedial prefrontal cortex (vmPFC) in mediating fear responses is well established, vmPFC has also been implicated in the regulation of reward-guided approach and extinction. Many studies have used indirect methods and simple behavioral procedures to study vmPFC, which leaves the literature incomplete. We recorded vmFPC neural activity during a complex cue-driven combined approach and avoidance task and during extinction. Surprisingly, we found very little vmPFC modulation to cues predicting avoidable shock, whereas cues predicting reward approach robustly modulated vmPFC firing in a response- and outcome-selective manner. This suggests a more complex role for vmPFC than current theories suggest, specifically regarding context-specific behavioral optimization.
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Husband’s involvement with mother’s awareness and knowledge of newborn danger signs in facility-based childbirth settings: a cross-sectional study from rural Bangladesh
The aim of this study was to examine the association between husband involvement and maternal awareness and knowledge of newborn danger signs. This cross-sectional study was conducted in three rural hospitals ...
https://ift.tt/2KLlJZ8
ICAM-1-related long non-coding RNA: promoter analysis and expression in human retinal endothelial cells
Regulation of intercellular adhesion molecule (ICAM)-1 in retinal endothelial cells is a promising druggable target for retinal vascular diseases. The ICAM-1-related (ICR) long non-coding RNA stabilizes ICAM-1...
https://ift.tt/2G0fBJ0
Assessment of the Cytotoxic and Immunomodulatory Effects of Substances in Human Precision-cut Lung Slices
In view of the 3Rs principle, respiratory models as alternatives to animal studies are evolving. Especially for risk assessment of respiratory substances, there is a lack of appropriate assays. Here, we describe the use of human precision-cut lung slices for the assessment of airborne substances.
https://ift.tt/2Io0yho
Estimation of spatio-temporal parameters of gait from magneto-inertial measurement units: multicenter validation among Parkinson, mildly cognitively impaired and healthy older adults
The use of miniaturized magneto-inertial measurement units (MIMUs) allows for an objective evaluation of gait and a quantitative assessment of clinical outcomes. Spatial and temporal parameters are generally r...
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Hemodynamic effects of perfusion level of peripheral ECMO on cardiovascular system
Peripheral ECMO is an effective cardiopulmonary support in clinical. The perfusion level could directly influence the performances and complications. However, there are few studies on the effects of the perfus...
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Correction to: Secondary B-cell lymphoma associated with the Epstein-Barr virus in chronic lymphocytic leukemia patients
The article Secondary B-cell lymphoma associated with the Epstein-Barr virus in chronic lymphocytic leukemia patients.
https://ift.tt/2I2b5zv
Long-Term Depression Is Independent of GluN2 Subunit Composition
NMDA receptors (NMDARs) mediate both long-term potentiation and long-term depression (LTD) and understanding how a single receptor can initiate both phenomena remains a major question in neuroscience. A prominent hypothesis implicates the NMDAR subunit composition, specifically GluN2A and GluN2B, in dictating the rules of synaptic plasticity. However, studies testing this hypothesis have yielded inconsistent and often contradictory results, especially for LTD. These inconsistent results may be due to challenges in the interpretation of subunit-selective pharmacology and in dissecting out the contributions of differential channel properties versus the interacting proteins unique to GluN2A or GluN2B. In this study, we address the pharmacological and biochemical challenges by using a single-neuron genetic approach to delete NMDAR subunits in conditional knock-out mice. In addition, the recently discovered non-ionotropic nature of NMDAR-dependent LTD allowed the rigorous assessment of unique subunit contributions to NMDAR-dependent LTD while eliminating the variable of differential charge transfer. Here we find that neither the GluN2A nor the GluN2B subunit is strictly necessary for either non-ionotropic or ionotropic LTD.
SIGNIFICANCE STATEMENT NMDA receptors are key regulators of bidirectional synaptic plasticity. Understanding the mechanisms regulating bidirectional plasticity will guide development of therapeutic strategies to treat the dysfunctional synaptic plasticity in multiple neuropsychiatric disorders. Because of the unique properties of the NMDA receptor GluN2 subunits, they have been postulated to differentially affect synaptic plasticity. However, there has been significant controversy regarding the roles of the GluN2 subunits in synaptic long term depression (LTD). Using single-neuron knock-out of the GluN2 subunits, we show that LTD requires neither GluN2A nor GluN2B.
https://ift.tt/2IstwN7
Restoring Tip60 HAT/HDAC2 Balance in the Neurodegenerative Brain Relieves Epigenetic Transcriptional Repression and Reinstates Cognition
Cognitive decline is a debilitating hallmark during preclinical stages of Alzheimer's disease (AD), yet the causes remain unclear. Because histone acetylation homeostasis is critical for mediating epigenetic gene control throughout neuronal development, we postulated that its misregulation contributes to cognitive impairment preceding AD pathology. Here, we show that disruption of Tip60 histone acetlytransferase (HAT)/histone deacetylase 2 (HDAC2) homeostasis occurs early in the brain of an AD-associated amyloid precursor protein (APP) Drosophila model and triggers epigenetic repression of neuroplasticity genes well before Aβ plaques form in male and female larvae. Repressed genes display enhanced HDAC2 binding and reduced Tip60 and histone acetylation enrichment. Increasing Tip60 in the AD-associated APP brain restores Tip60 HAT/HDAC2 balance by decreasing HDAC2 levels, reverses neuroepigenetic alterations to activate synaptic plasticity genes, and reinstates brain morphology and cognition. Such Drosophila neuroplasticity gene epigenetic signatures are conserved in male and female mouse hippocampus and their expression and Tip60 function is compromised in hippocampus from AD patients. We suggest that Tip60 HAT/HDAC2-mediated epigenetic gene disruption is a critical initial step in AD that is reversed by restoring Tip60 in the brain.
SIGNIFICANCE STATEMENT Mild cognitive impairment is a debilitating hallmark during preclinical stages of Alzheimer's disease (AD), yet its causes remain unclear. Although recent findings support elevated histone deacetylase 2 (HDAC2) as a cause for epigenetic repression of synaptic genes that contribute to cognitive deficits, whether alterations in histone acetlytransferase (HAT) levels that counterbalance HDAC2 repressor action occur and the identity of these HATs remain unknown. We demonstrate that disruption of Tip60 HAT/HDAC2 homeostasis occurs early in the AD Drosophila brain and triggers epigenetic repression of neuroplasticity genes before Aβ plaques form. Increasing Tip60 in the AD brain restores Tip60 HAT/HDAC2 balance, reverses neuroepigenetic alterations to activate synaptic genes, and reinstates brain morphology and cognition. Our data suggest that disruption of the Tip60 HAT/HDAC2 balance is a critical initial step in AD.
https://ift.tt/2K3yih6
Mortality trends among people with hepatitis B and C: a population-based linkage study, 1993-2012
This study evaluated cause-specific mortality trends including liver-related mortality among people with a hepatitis B virus (HBV) and hepatitis C virus (HCV) notification in New South Wales, Australia.
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Preparing Fresh Retinal Slices from Adult Zebrafish for Ex Vivo Imaging Experiments
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Correction to: European radiographers’ challenges from mammography education and clinical practice—an integrative review
Affiliation number 2 was rendered incorrectly.
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Australian integrative oncology services: a mixed-method study exploring the views of cancer survivors
The significant use of traditional and complementary medicine (T&CM) by cancer survivors is well documented. The aim of this study was to explore cancer survivors' views on integrating T&CM services with conve...
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Antrodia cinnamomea extract inhibits the proliferation of tamoxifen-resistant breast cancer cells through apoptosis and skp2/microRNAs pathway
Breast cancer is the most common cancer in women and affects 1.38 million women worldwide per year. Antiestrogens such as tamoxifen, a selective estrogen receptor (ER) modulator, are widely used in clinics to ...
https://ift.tt/2jLYzpp
A terpenoid isolated from sarang semut (Myrmecodia pendans) bulb and its potential for the inhibition and eradication of Streptococcus mutans biofilm
Dental caries remains a serious problem due to its detrimental effects on individual health and quality of life. The bulbs of Myrmecodia pendans (Merr & Perry), native plants of Papua, have been used as natural r...
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Respiratory and GIT tract immune responses of broiler chickens following experimental infection with Newcastle disease’s virus
Abstract
Newcastle disease causes a lymphoproliferative response in the tracheal and intestinal mucosa of the infected birds. In this study, the Hitchner B1 and I-2 vaccine and challenging of ND field strains were used to evaluate the populations of T lymphocyte subsets infiltrated intestinal and tracheal, also to shed some light on cell-mediated immune response using enzyme-linked immunosorbent assay (ELISA) detecting chicken's serum interferon-γ. Three hundred-day-old broilers were randomly divided into four groups. Groups 1 and 2 received I-2 and B1 vaccines, respectively, while groups 3 and 4 were challenged-unvaccinated and unchallenged-unvaccinated groups. Blood samples were taken from five random chicks and were then tested with ELISA test. Three chicks of each group were euthanized after vaccine administration and also challenging with acute virus. Interferon-γ changes were significant in time (p < 0.001). Totally, there was no significant difference between I-2 and B1 groups. The number of CD3+, CD4+, and CD8+ cells of I-2 and B1 vaccinated group's intestine and the trachea samples was significantly increased compared with the negative control group (p < 0.001). The results indicated the significant increase in CD4+ and CD8+ in intestinal and tracheal tissues, while the level of interferon-γ of the vaccinated group was more than the unvaccinated one. Finding no significant differences between the vaccinated groups indicated the potential of both vaccines in producing CD4+ and CD8+ in the tracheal and intestinal tissues and the equality of interferon-γ production in the sera.
https://ift.tt/2I5A0yc
Phase II study of adjuvant chemotherapy with S1 plus oxaliplatin for Chinese patients with gastric cancer
Abstract
Background
S-1 plus oxaliplatin(SOX) has been demonstrated to be effective and well tolerated for patients with metastatic gastric cancer. We conducted this phase II study to evaluate the feasibility of SOX as adjuvant chemotherapy for gastric cancer after curative resection.
Methods
Adjuvant chemotherapy consisted of six to eight cycles of S-1 plus oxaliplatin. Oxaliplatin was administered intravenously at a dose of 130 mg/m2 on day 1. S-1 was administered orally at a dose of 70 mg/m2 daily from day 1 to 14 of a 3-week cycle. A total of 58 patients were enrolled in this study. The primary end point of the trial was the treatment completion rate for six cycles. Secondary endpoints were safety, 1-year and 3-year of disease free survival (DFS) and overall survival (OS).
Results
A total of 58 patients were enrolled and 54 patients have been analysed. The completion rate of six cycles was 72.2%. Grade 4 toxicities included neutropenia (1.9%) and thrombocytopenia (3.7%). Grade 3 toxicities included leukopenia (5.6%), neutropenia (24.1%), thrombocytopenia (13.0%), nausea (7.4%), vomiting 13.0%), and diarrhea (13.0%). There was no grade 3 or higher peripheral sensory neuropathy and treatment-related death. The median follow-up time was 42.4 months. 1-year and 3-year DFS rate were 85.2 and 75.9%, respectively.1-year and 3-year OS were 98.1 and 85.2%, respectively.
Conclusion
Adjuvant chemotherapy for GC with S-1 plus oxaliplatin is safe and feasible in Chinese patients. The optimal dose of oxaliplatin and optimal cycles of treatment still need to be further investigated.
Trial registration
clinicaltrials.gov identifier NCT01542294. Trial registration date: 03/02/2012.
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Clinical decision making in cancer care: a review of current and future roles of patient age
Abstract
Background
Patient age is among the most controversial patient characteristics in clinical decision making. In personalized cancer medicine it is important to understand how individual characteristics do affect practice and how to appropriately incorporate such factors into decision making. Some argue that using age in decision making is unethical, and how patient age should guide cancer care is unsettled. This article provides an overview of the use of age in clinical decision making and discusses how age can be relevant in the context of personalized medicine.
Methods
We conducted a scoping review, searching Pubmed for English references published between 1985 and May 2017. References concerning cancer, with patients above the age of 18 and that discussed age in relation to diagnostic or treatment decisions were included. References that were non-medical or concerning patients below the age of 18, and references that were case reports, ongoing studies or opinion pieces were excluded. Additional references were collected through snowballing and from selected reports, guidelines and articles.
Results
Three hundred and forty-seven relevant references were identified. Patient age can have many and diverse roles in clinical decision making: Contextual roles linked to access (age influences how fast patients are referred to specialized care) and incidence (association between increasing age and increasing incidence rates for cancer); patient-relevant roles linked to physiology (age-related changes in drug metabolism) and comorbidity (association between increasing age and increasing number of comorbidities); and roles related to interventions, such as treatment (older patients receive substandard care) and outcome (survival varies by age).
Conclusions
Patient age is integrated into cancer care decision making in a range of ways that makes it difficult to claim age-neutrality. Acknowledging this and being more transparent about the use of age in decision making are likely to promote better clinical decisions, irrespective of one's normative viewpoint. This overview also provides a starting point for future discussions on the appropriate role of age in cancer care decision making, which we see as crucial for harnessing the full potential of personalized medicine.
https://ift.tt/2KJ418J
PDXliver: a database of liver cancer patient derived xenograft mouse models
Abstract
Background
Liver cancer is the second leading cause of cancer-related deaths and characterized by heterogeneity and drug resistance. Patient-derived xenograft (PDX) models have been widely used in cancer research because they reproduce the characteristics of original tumors. However, the current studies of liver cancer PDX mice are scattered and the number of available PDX models are too small to represent the heterogeneity of liver cancer patients. To improve this situation and to complement available PDX models related resources, here we constructed a comprehensive database, PDXliver, to integrate and analyze liver cancer PDX models.
Description
Currently, PDXliver contains 116 PDX models from Chinese liver cancer patients, 51 of them were established by the in-house PDX platform and others were curated from the public literatures. These models are annotated with complete information, including clinical characteristics of patients, genome-wide expression profiles, germline variations, somatic mutations and copy number alterations. Analysis of expression subtypes and mutated genes show that PDXliver represents the diversity of human patients. Another feature of PDXliver is storing drug response data of PDX mice, which makes it possible to explore the association between molecular profiles and drug sensitivity. All data can be accessed via the Browse and Search pages. Additionally, two tools are provided to interactively visualize the omics data of selected PDXs or to compare two groups of PDXs.
Conclusion
As far as we known, PDXliver is the first public database of liver cancer PDX models. We hope that this comprehensive resource will accelerate the utility of PDX models and facilitate liver cancer research. The PDXliver database is freely available online at: http://www.picb.ac.cn/PDXliver/
https://ift.tt/2rxHsL9
XPF polymorphism toward lung cancer susceptibility and survival in patients treated with platinum-based chemotherapy
Future Oncology, Ahead of Print.
https://ift.tt/2IbOxIo
Temozolomide rechallenge in recurrent glioblastoma: when is it useful?
Future Oncology, Ahead of Print.
https://ift.tt/2ruEvfs
Recent breakthroughs in metastatic uveal melanoma: a cause for optimism?
Future Oncology, Ahead of Print.
https://ift.tt/2I6taII
Overexpression of Fn14 in gliomas: tumor progression and poor prognosis
Future Oncology, Ahead of Print.
https://ift.tt/2IbOiNu
CXCL12 and CXCR4 polymorphisms and expressions in peripheral blood from patients of hepatocellular carcinoma
Future Oncology, Ahead of Print.
https://ift.tt/2ruEc4i
Diagnostic serum vitamin D level is not a reliable prognostic factor for resectable breast cancer
Future Oncology, Ahead of Print.
https://ift.tt/2I8DMH5
Assessing the kidney function parameters glomerular filtration rate and effective renal plasma flow with dynamic FDG-PET/MRI in healthy subjects
Abstract
Background
A method was developed to assess the kidney parameters glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) from 2-deoxy-2-[18F]fluoro-d-glucose (FDG) concentration behavior in kidneys, measured with positron emission tomography (PET) scans.
Twenty-four healthy adult subjects prospectively underwent dynamic simultaneous PET/magnetic resonance imaging (MRI) examination. Time activity curves (TACs) were obtained from the dynamic PET series, with the guidance of MR information. Patlak analysis was performed to determine the GFR, and based on integrals, ERPF was calculated. Results were compared to intra-individually obtained reference values determined from venous blood samples.
Results
Total kidney GFR and ERPF as estimated by dynamic PET/MRI were highly correlated to their reference values (r = 0.88/p < 0.0001 and r = 0.82/p < 0.0001, respectively) with no significant difference between their means.
Conclusions
The study is a proof of concept that GFR and ERPF can be assessed with dynamic FDG PET/MRI scans in healthy kidneys. This has advantages for patients getting a routine scan, where additional examinations for kidney function estimation could be avoided. Further studies are required for transferring this PET/MRI method to PET/CT applications.
https://ift.tt/2I2GQs3
SPIN1, negatively regulated by miR-148/152, enhances Adriamycin resistance via upregulating drug metabolizing enzymes and transporter in breast cancer
Abstract
Background
Spindlin1 (SPIN1), a protein highly expressed in several human cancers, has been correlated with tumorigenesis and development. Alterations of drug metabolizing enzymes and drug transporters are major determinants of chemoresistance in tumor cells. However, whether the metabolizing enzymes and transporters are under the control of SPIN1 in breast cancer chemoresistance has not yet been defined.
Methods
SPIN1 expression in breast cancer cells and tissues was detected by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Chemosensitivity assays in vitro and in vivo were performed to determine the effect of SPIN1 on Adriamycin resistance. Downstream effectors of SPIN1 were screened by microarray and confirmed by qRT-PCR and Western blot. Luciferase assay and Western blot were used to identify miRNAs regulating SPIN1.
Results
We showed that SPIN1 was significantly elevated in drug-resistant breast cancer cell lines and tissues, compared with the chemosensitive ones. SPIN1 enhanced Adriamycin resistance of breast cancer cells in vitro, and downregulation of SPIN1 by miRNA could decrease Adriamycin resistance in vivo. Mechanistically, drug metabolizing enzymes and transporter CYP2C8, UGT2B4, UGT2B17 and ABCB4 were proven to be downstream effectors of SPIN1. Notably, SPIN1 was identified as a direct target of the miR-148/152 family (miR-148a-3p, miR-148b-3p and miR-152-3p). As expected, miR-148a-3p, miR-148b-3p or miR-152-3p could increase Adriamycin sensitivity in breast cancer cells in vitro. Moreover, high expression of SPIN1 or low expression of the miR-148/152 family predicted poorer survival in breast cancer patients.
Conclusions
Our results establish that SPIN1, negatively regulated by the miR-148/152 family, enhances Adriamycin resistance in breast cancer via upregulating the expression of drug metabolizing enzymes and drug transporter.
https://ift.tt/2KMvgiI
The dysregulation of tRNAs and tRNA derivatives in cancer
Abstract
Transfer RNAs (tRNAs), traditionally considered to participate in protein translation, were interspersed in the entire genome. Recent studies suggested that dysregulation was observed in not only tRNAs, but also tRNA derivatives generated by the specific cleavage of pre- and mature tRNAs in the progression of cancer. Accumulating evidence had identified that certain tRNAs and tRNA derivatives were involved in proliferation, metastasis and invasiveness of cancer cell, as well as tumor growth and angiogenesis in several malignant human tumors. This paper reviews the importance of the dysregulation of tRNAs and tRNA derivatives during the development of cancer, such as breast cancer, lung cancer, and melanoma, aiming at a better understanding of the tumorigenesis and providing new ideas for the treatment of these cancers.
https://ift.tt/2rxn39d
10 rules for EMS at the emergency department
Behave, play nice and show some respect to strive for fellowship with doctors and nurses on hospital grounds
https://ift.tt/2jKVmX7
Futile Recanalization after Endovascular Therapy in Acute Ischemic Stroke
Early recanalization after endovascular treatment could improve the prognosis of acute ischemia stroke. Futile recanalization often occurred which was one of the main causes of failure. By now the mechanisms of futile recanalization were not clear. They are probably concerned with bad collateral circulation, subacute reocclusion, large hypoperfusion volumes, microvascular compromise, and impaired cerebral autoregulation. Previous research found that some of the image markers could be used as the accurate predictors for poor prognosis after successful treatment in order to identify the patients who were not suitable for recanalization and reduce some of the unnecessary cost. Predictors for futile recanalization mentioned in our article can be used for supplement to make decision for endovascular treatment.
https://ift.tt/2I40Nig
Associations of dietary intake and supplement use with post-therapy cognitive recovery in breast cancer survivors
Abstract
Purpose
Cognitive impairment induced by cancer therapy is common and can be long lasting after completion of therapy. Little is known on factors that influence recovery from the impairment. We evaluated the associations of dietary intake and supplement use with post-therapy cognitive recovery in a large cohort of breast cancer survivors.
Methods
This study included 1047 breast cancer patients aged 20–75 who were recruited to the Shanghai Breast Cancer Survival Study between 2002 and 2006 at approximately 6.5 months post-cancer diagnosis. Two cognitive assessments covering immediate memory, delayed memory, verbal fluency, and attention, were conducted at 18 and 36 months post-diagnosis. We used food frequency questionnaire to collect information on their dietary intake and supplement use between 18 and 36 months post-diagnosis. Linear regression models were used to examine the associations of dietary intake and supplement use with mean cognitive scores at 36 months post-diagnosis and with differences in cognitive scores between 18 and 36 months post-diagnosis.
Results
Higher vegetable, fruit and fish intake, supplementation with vitamin B and vitamin E, and tea drinking were associated with higher cognitive scores, while alcohol drinking was associated with lower cognitive scores at 36 months post-diagnosis. Vegetable intake was positively associated with improvement in verbal fluency, while tea drinking and fish oil supplementation were associated with greater improvements in delayed memory between 18 and 36 months post-diagnosis.
Conclusions
Our results indicate that higher vegetable intake, tea drinking, and fish oil supplementation may help post-therapy cognitive recovery for cancer patients.
https://ift.tt/2FYtuYh
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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