Medicine by Alexandros G.Sfakianakis: 10/19/18

Παρασκευή 19 Οκτωβρίου 2018

Platelets: the holy grail in cancer blood biomarker research?

Abstract

We would like to promote the fact that platelets are increasingly emerging as a rich source of potential biomarkers for cancer. Blood platelets contain vast amounts of bioactive proteins, such as growth factors, chemokines, and cytokines. These proteins are either synthesized by the megakaryocytes that produce the platelets or are sequestered by the circulating platelets from the blood, in which case these proteins may originate from the tumor. Recent studies in patients have demonstrated that the presence of cancer influences multiple platelet characteristics (e.g., platelet count, volume, activation status, proteins, and RNA content). Interestingly, these changes happened already in early stages of the disease before metastasis had occurred. Additionally, exploiting these platelet alterations enabled discrimination of patients with early-stage cancer from healthy sex- and age-matched individuals. Therefore, we challenge clinicians and researchers to look beyond traditional fluid sources such as plasma or serum, and to take platelets and their content into account as they may become the holy grail in cancer blood biomarker research.

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Safety and efficacy of lifitegrast 5% ophthalmic solution in contact lens discomfort

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Purpura fulminans with Lemierre’s syndrome caused by Gemella bergeri and Eikenella corrodens: a case report

Gemella bergeri is one of the nine species of the genus Gemella and is relatively difficult to identify. We herein describe the first case of septic shock due to a Gemella bergeri coinfection with Eikenella corro...

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A remarkable insight into the cancer journey of Barbara Moss

Future Oncology, Ahead of Print.

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Sequential treatment with afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: an observational study

Future Oncology, Ahead of Print.

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Outcomes of Stable Multiple Sclerosis Patients Staying on Initial Interferon Beta Therapy Versus Switching to Another Interferon Beta Therapy: A US Claims Database Study

Abstract

Introduction

This study was designed to assess real-world outcomes of patients with multiple sclerosis (MS) who were stable on interferon (IFN) beta therapy in the year prior to switching to another IFN beta therapy versus those who continued on the initial treatment.

Methods

This study used administrative claims from MarketScan Commercial Claims and Encounters Database, from January 1, 2010, to March 31, 2015, to identify MS patients aged 18–64 years who remained relapse free for at least 1 year while continuously treated with an IFN beta therapy. Stable patients remaining on their initial IFN beta therapy (no-switch patients) were matched with stable patients who switched IFN beta therapy (switch patients) using propensity score matching (first claim = index date). Outcome measures included annualized relapse rate (ARR), the percentage of patients who relapsed, medication possession ratio, and the proportion of days covered and were measured during the year following the index date.

Results

This study identified 531 patients in the no-switch group and 177 patients in the switch group, with subsets of 270 patients in the no-switch group and 90 patients in the switch group stable on intramuscular (IM) IFN beta-1a therapy. All outcomes during the follow-up year were significantly better in the no-switch group than in the switch group. For all patients, ARR in the switch group was more than twice that in the no-switch group (P = 0.002). For patients stable on IM IFN beta-1a at baseline, ARR was twice as high in the switch group as in the no-switch group (P = 0.012).

Conclusion

Among all patients stable on IFN beta therapy and the subset stable on IM IFN beta therapy in particular, those who remained on therapy had significantly better outcomes than those who switched to another IFN beta therapy.

Funding

Biogen (Cambridge, MA, USA).

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Diurnal and 24-h Intraocular Pressures in Glaucoma: Monitoring Strategies and Impact on Prognosis and Treatment

Abstract

The present review casts a critical eye on intraocular pressure (IOP) monitoring and its value in current and future glaucoma care. Crucially, IOP is not fixed, but varies considerably during the 24-h cycle and between one visit and another. Consequently, a single IOP measurement during so-called office hours is insufficient to characterize the real IOP pathology of a patient with glaucoma. To date IOP remains the principal and only modifiable risk factor for the development and progression of glaucoma. Only by evaluating IOP characteristics (mean, peak and fluctuation of IOP) at diagnosis and after IOP-lowering interventions can we appreciate the true efficacy of therapy. Unfortunately, a major limiting factor in glaucoma management is lack of robust IOP data collection. Treatment decisions, advancement of therapy and even surgery are often reached on the basis of limited IOP evidence. Clearly, there is much room to enhance our decision-making and to develop new algorithms for everyday practice. The precise way in which daytime IOP readings can be used as predictors of night-time or 24-h IOP characteristics remains to be determined. In practice it is important to identify those at-risk glaucoma patients for whom a complete 24-h curve is necessary and to distinguish them from those for whom a daytime curve consisting of three IOP measurements (at 10:00, 14:00 and 18:00) would suffice. By employing a staged approach in determining the amount of IOP evidence needed and the rigour required for our monitoring approach for the individual patient, our decisions will be based on more comprehensive data, while at the same time this will optimize use of resources. The patient's clinical picture should be the main factor that determines which method of IOP monitoring is most appropriate. A diurnal or ideally a 24-h IOP curve will positively impact the management of glaucoma patients who show functional/anatomical progression, despite an apparently acceptable IOP in the clinic. The potential impact of nocturnal IOP elevation remains poorly investigated. The ideal solution in the future is the development of non-invasive methods for obtaining continuous, Goldmann equivalent IOP data on all patients prior to key treatment decisions. Moreover, an important area of future research is to establish the precise relationship between 24-h IOP characteristics and glaucoma progression.

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RUNX1-ETO Upregulates CCND2 to Drive Leukemogenesis [Research Watch]

An RNAi screen identified CCND2 as a RUNX1–ETO target gene required for leukemia maintenance.

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IRE1{alpha}-XBP1 Suppresses the Antitumor Activity of T Cells [Research Watch]

Endoplasmic reticulum stress activates IRE1α–XBP1 in ovarian cancer T cells to reduce antitumor activity.

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Inhibiting C5a Enhances Chemotherapeutic Efficacy [Research Watch]

C5aR1 signaling in macrophages and mast cells promotes squamous cell carcinoma (SCC) tumorigenesis.

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Neoadjuvant Immune Checkpoint Blockade Has Antitumor Activity [Research Watch]

Neoadjuvant immunotherapy induces a stronger immune response than adjuvant immunotherapy.

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MYC Interacts with the G9a Methyltransferase to Repress Target Genes [Research Watch]

G9a binds preferentially to MYC at MYC-repressed target genes, enhancing transcriptional repression.

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Innate immune priming of insulin secretion

Elise Dalmas

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Oxeiptosis: a discreet way to respond to radicals

Pietro Scaturro | Andreas Pichlmair

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CDC: First U.S. Case of Rat-Borne Andes Virus Diagnosed

FRIDAY, Oct. 19, 2018 -- The first confirmed U.S. case of a virus carried by South American rodents occurred earlier this year, the U.S. Centers for Disease Control and Prevention says. Doctors at a Delaware hospital diagnosed Andes virus in a...

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Physical Therapy an Option for Nonobstructive Meniscal Tears

FRIDAY, Oct. 19, 2018 -- Physical therapy (PT) is non-inferior to arthroscopic partial meniscectomy (APM) for patients with nonobstructive meniscal tears, according to a study published in the Oct. 2 issue of the Journal of the American Medical...

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Limited Success for Changing Diet and Exercise Among Nurses

FRIDAY, Oct. 19, 2018 -- Implementation of a workplace intervention to change diet and physical activity (PA) behavior was partially successful among nurses, with the ability to change both diet and PA at the same time described as challenging,...

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CDC: Vaccination Rates More Than 95 Percent for Kindergartners

FRIDAY, Oct. 19, 2018 -- Overall vaccination coverage is high among the nation's kindergarten students, according to research published in the Oct. 12 issue of the U.S. Centers for Disease Control and Prevention's Morbidity and Mortality Weekly...

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Variability in Geographic Availability of New Antibiotics

FRIDAY, Oct. 19, 2018 -- There is considerable variability in the geographic availability of antibiotics, according to a study published online Oct. 16 in PLOS ONE. Cecilia Kållberg, from the University of Oslo in Norway, and colleagues examined...

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TGF{beta}-activated USP27X deubiquitinase regulates cell migration and chemoresistance via stabilization of Snail1

In cancer cells, epithelial-to-mesenchymal transition (EMT) is controlled by Snail1, a transcriptional factor also required for the activation of cancer-associated fibroblasts (CAF). Snail1 is short-lived in normal epithelial cells as a consequence of its coordinated and continuous ubiquitination by several F-box specific E3 ligases, but its degradation is prevented in cancer cells and in activated fibroblasts. Here we performed an siRNA screen and identified USP27X as a deubiquitinase that increases Snail1 stability. Expression of USP27X in breast and pancreatic cancer cell lines and tumors positively correlated with Snail1 expression levels. Accordingly, downregulation of USP27X decreased Snail1 protein in several tumor cell lines. USP27X depletion impaired Snail1-dependent cell migration and invasion and metastasis formation and increased cellular sensitivity to cisplatin. USP27X was upregulated by TGFβ during EMT and was required for TGFβ-induced expression of Snail1 and other mesenchymal markers in epithelial cells and CAF. In agreement with this, depletion of USP27X prevented TGFβ-induced EMT and fibroblast activation. Collectively, these results indicate that USP27X is an essential protein controlling Snail1 expression and function, and may serve as a target for inhibition of Snail1-dependent tumoral invasion and chemoresistance.

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The Relationship Between Bone Mineral Density and Type 2 Diabetes in Obese Children and Adolescents at the Time of Initial Diagnosis

Horm Metab Res
DOI: 10.1055/a-0755-2799

Long-term effects of type 2 diabetes mellitus (T2D) on bone health remain unclear. The objective of this study was to assess the possible association of bone mineral density (BMD) at multiple sites with T2D after correcting for several potential confounders such as age, sex, Tanner stage, and BMI known to affect BMD in adolescents with newly developed T2D. In this cross-sectional study, 17 children and adolescents with T2D and 59 age, sex, and BMI-matched controls were included. All subjects underwent dual-energy X-ray absorptiometry to measure regional and whole-body composition with Lunar Prodigy at the time of initial diagnosis. A BMD Z-score was calculated using data from healthy Korean children and adolescents after adjusting for height-for-age. The mean age of all subjects was 12.9±2.4 years (range, 8.3–18.3 years). BMDht Z-scores for lumbar spine and total body after adjusted for age, sex, BMI SDS, and Tanner stage were not significantly different between patients and controls. However, BMDht Z-scores for femur neck and bone mineral apparent density (BMAD) Z-scores of lumbar spine were significantly lower in T2D patients than those in healthy controls. HOMA-IR or HbA1c was not associated with BMDht Z-scores at multiple sites. BMDht Z-scores at multiple sites except femur neck in adolescents with newly developed T2D were similar to those in obese controls after adjustment for potential confounders.
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Article in Thieme eJournals:
Table of contents | Abstract | Full text

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Protecting the Beans: Perioperative Acute Kidney injury

No abstract available

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Update on Perioperative Acute Kidney Injury

Acute kidney injury (AKI) in the perioperative period is a common complication and is associated with increased morbidity and mortality. A standard definition and staging system for AKI has been developed, incorporating a reduction of the urine output and/or an increase of serum creatinine. Novel biomarkers may detect kidney damage in the absence of a change in function and can also predict the development of AKI. Several specific considerations for AKI risk are important in surgical patients. The surgery, especially major and emergency procedures in critically ill patients, may cause AKI. In addition, certain comorbidities, such as chronic kidney disease and chronic heart failure, are important risk factors for AKI. Diuretics, contrast agents, and nephrotoxic drugs are commonly used in the perioperative period and may result in a significant amount of in-hospital AKI. Before and during surgery, anesthetists are supposed to optimize the patient, including preventing and treating a hypovolemia and correcting an anemia. Intraoperative episodes of hypotension have to be avoided because even short periods of hypotension are associated with an increased risk of AKI. During the intraoperative period, urine output might be reduced in the absence of kidney injury or the presence of kidney injury with or without fluid responsiveness. Therefore, fluids should be used carefully to avoid hypovolemia and hypervolemia. The Kidney Disease: Improving Global Outcomes guidelines suggest implementing preventive strategies in high-risk patients, which include optimization of hemodynamics, restoration of the circulating volume, institution of functional hemodynamic monitoring, and avoidance of nephrotoxic agents and hyperglycemia. Two recently published studies found that implementing this bundle in high-risk patients reduced the occurrence of AKI in the perioperative period. In addition, the application of remote ischemic preconditioning has been studied to potentially reduce the incidence of perioperative AKI. This review discusses the epidemiology and pathophysiology of surgery-associated AKI, highlights the importance of intraoperative oliguria, and emphasizes potential preventive strategies.

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Balancing Act: Multimodal General Anesthesia

No abstract available

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Multimodal General Anesthesia: Theory and Practice

Balanced general anesthesia, the most common management strategy used in anesthesia care, entails the administration of different drugs together to create the anesthetic state. Anesthesiologists developed this approach to avoid sole reliance on ether for general anesthesia maintenance. Balanced general anesthesia uses less of each drug than if the drug were administered alone, thereby increasing the likelihood of its desired effects and reducing the likelihood of its side effects. To manage nociception intraoperatively and pain postoperatively, the current practice of balanced general anesthesia relies almost exclusively on opioids. While opioids are the most effective antinociceptive agents, they have undesirable side effects. Moreover, overreliance on opioids has contributed to the opioid epidemic in the United States. Spurred by concern of opioid overuse, balanced general anesthesia strategies are now using more agents to create the anesthetic state. Under these approaches, called "multimodal general anesthesia," the additional drugs may include agents with specific central nervous system targets such as dexmedetomidine and ones with less specific targets, such as magnesium. It is postulated that use of more agents at smaller doses further maximizes desired effects while minimizing side effects. Although this approach appears to maximize the benefit-to-side effect ratio, no rational strategy has been provided for choosing the drug combinations. Nociception induced by surgery is the primary reason for placing a patient in a state of general anesthesia. Hence, any rational strategy should focus on nociception control intraoperatively and pain control postoperatively. In this Special Article, we review the anatomy and physiology of the nociceptive and arousal circuits, and the mechanisms through which commonly used anesthetics and anesthetic adjuncts act in these systems. We propose a rational strategy for multimodal general anesthesia predicated on choosing a combination of agents that act at different targets in the nociceptive system to control nociception intraoperatively and pain postoperatively. Because these agents also decrease arousal, the doses of hypnotics and/or inhaled ethers needed to control unconsciousness are reduced. Effective use of this strategy requires simultaneous monitoring of antinociception and level of unconsciousness. We illustrate the application of this strategy by summarizing anesthetic management for 4 representative surgeries.

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Single-incision Laparoscopy Versus Multiport Laparoscopy for Colonic Surgery: A Multicenter, Double-blinded, Randomized Controlled Trial

Objective: To compare outcome of single-port laparoscopy (SPL) and multiport laparoscopy (MPL) laparoscopy for colonic surgery. Summary of Background Data: Benefits of SPL over MPL are yet to be demonstrated in large randomized trials. Methods: In this prospective, double-blinded, superiority trial, patients undergoing laparoscopic colonic resection for benign or malignant disease were randomly assigned to SPL or MPL (NCT01959087). Primary outcome was length of theoretical hospital stay (LHS). Results: One hundred twenty-eight patients were randomized and 125 analyzed: 62 SPL and 63 MPL, including 91 right (SPL: n = 44, 71%; MPL: n = 47, 75%) and 34 left (SPL: n = 18, 29%; MPL: n = 16, 25%) colectomies, performed for Crohn disease (n = 53, 42%), cancer (n = 36, 29%), diverticulitis (n = 21, 17%), or benign neoplasia (n = 15, 12%). Additional port insertion was required in 5 (8%) SPL patients and conversion to laparotomy occurred in 7 patients (SPL: n = 3, 5%; MPL: n = 4, 7%; P = 1.000). Total length of skin incision was significantly shorter in the SPL group [SPL: 56 ± 41 (range, 30–300) mm; MPL: 87 ± 40 (50–250) mm; P

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Balancing Act: Multimodal General Anesthesia

No abstract available

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Postoperative Hypotension and Surgical Site Infections After Colorectal Surgery: A Retrospective Cohort Study

BACKGROUND: Hypotension compromises local tissue perfusion, thereby reducing tissue oxygenation. Hypotension might thus be expected to promote infection. Hypotension on surgical wards, while usually less severe than intraoperative hypotension, is common and often prolonged. In this retrospective cohort study, we tested the hypotheses that there is an association between surgical site infections and low postoperative time-weighted average mean arterial pressure and/or postoperative minimum mean arterial pressure. METHODS: We considered patients who had colorectal surgery lasting ≥1 hour at the Cleveland Clinic between 2009 and 2013. We defined blood pressure exposures as time-weighted average (primary) and minimum mean arterial pressure (secondary) within 72 hours after surgery. We assessed associations between continuous blood pressure exposures with a composite of deep and superficial surgical site infection using separate severity-weighted average relative effect generalized estimating equations models, each using an unstructured correlation structure and adjusting for potentially confounding variables. RESULTS: A total of 5896 patients were eligible for analysis. Time-weighted mean arterial pressure and surgical site infection were not significantly associated, with an estimated odds ratio (95% CI) of 1.03 (0.99–1.08) for a 5-mm Hg decrease (P = .16). However, there was a significant inverse association between minimum postoperative mean arterial pressure and infection, with an estimated odds ratio of 1.08 (1.03–1.12) per 5-mm Hg decrease (P = .001). CONCLUSIONS: Postoperative time-weighted mean arterial pressure was not associated with surgical site infection, but lowest postoperative mean arterial pressure was. Whether the relationship is causal remains to be determined.

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71st World Health Assembly, Geneva, Switzerland 2018

No abstract available

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In Response

No abstract available

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Protecting the Beans: Perioperative Acute Kidney injury

No abstract available

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In Response

No abstract available

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“Randomization at the Expense of Relevance.” L. J. Cronbach and Intravenous Acetaminophen as an Opioid-Sparing Adjuvant

No abstract available

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American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Postoperative Gastrointestinal Dysfunction Within an Enhanced Recovery Pathway for Elective Colorectal Surgery: Erratum

No abstract available

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Preoperative Intravenous Iron to Enhance a Blood Management Program: Is It All in “Vein”?

No abstract available

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Perioperative Two-Dimensional Transesophageal Echocardiography: A Practical Handbook, 2nd ed

No abstract available

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Multimodal General Anesthesia: A Principled Approach to Producing the Drug-Induced, Reversible Coma of Anesthesia

No abstract available

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In Response

No abstract available

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Why Cost-Effectiveness?

No abstract available

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Nitrous Oxide Supply Systems

No abstract available

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Intraoperative Oliguria: Physiological or Beginning Acute Kidney Injury?

No abstract available

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Surveying the Literature: Synopsis of Recent Key Publications

No abstract available

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Anesthesia: The Gift of Oblivion and the Mystery of Consciousness

No abstract available

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Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival: A Planned Subanalysis of the ENIGMA-II Trial

BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs). RESULTS: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55–4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26–3.92]). Patients who suffered a MAPE with troponin elevation but without MI had the highest risk of death (n = 116) (aHR, 4.29 [95% CI, 2.89–6.36]). These 4 types of adverse events similarly affected 1-year disability-free survival. CONCLUSIONS: MACEs and MAPEs occur at similar frequencies and affect survival to a similar degree. All 3 types of postoperative troponin elevation in this analysis were associated, to varying degrees, with increased risk of death and disability.

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In Response

No abstract available

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In Response

No abstract available

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Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium

Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework.

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Coping with Incongruence: Mirror Therapy to Manage the Phantom Limb Phenomenon in Pediatric Amputee Patients

In pediatric patients with cancer-related amputations, the incidence of "phantom limb" pain is close to 90% (1). Although its physiopathology has not been fully explained, Mirror Therapy (MT), in conjunction with other treatments, has shown promising results in adults. In children, data is more limited and there are no controlled, prospective studies proving its efficacy, nor is there a standard for when it should be initiated, or its frequency or duration of the sessions (2,3).

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Predictors of Respiratory Improvement 1 Week after Ligation of Patent Ductus Arteriosus in Preterm Infants

To characterize preterm infants that demonstrates respiratory improvement 7 days after ligation of a patent ductus arteriosus (PDA).

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Copper Beaten Skull

A 5-year-old boy was referred for evaluation of dysmorphic facial features. Examination revealed a small forehead, bilateral proptosis, hypertelorism, flat nasal bridge, hypoplasia of the maxilla, and overcrowding of teeth. Near similar facial features were seen in his mother and younger brother. Genetic evaluation of the brothers and mother revealed FGFR2 10q26.13 gene mutation. Crouzon syndrome was diagnosed. This syndrome is characterized by premature craniosynostosis and inherited as an autosomal-dominant trait.

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Preparation of Chloroplast Sub-compartments from Arabidopsis for the Analysis of Protein Localization by Immunoblotting or Proteomics

Here, we describe a method to purify intact chloroplasts from Arabidopsis leaves and their three main sub-compartments (envelope, stroma, and thylakoids), using a combination of differential centrifugations, continuous Percoll gradients, and discontinuous sucrose gradients. The method is valuable for subplastidial and subcellular localization of proteins by immunoblotting and proteomics.

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A joint resource allocation method for multiple targets tracking in distributed MIMO radar systems

In order to simultaneously improve system performance and resource utilization of distributed multiple-input multiple-output (MIMO) radar systems, a joint resource allocation method is proposed to address the ...

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Communication efficient distributed weighted non-linear least squares estimation

The paper addresses design and analysis of communication-efficient distributed algorithms for solving weighted non-linear least squares problems in multi-agent networks. Communication efficiency is highly relevan...

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Capture and Identification of RNA-binding Proteins by Using Click Chemistry-assisted RNA-interactome Capture (CARIC) Strategy

A detailed protocol for applying the click chemistry-assisted RNA-interactome capture (CARIC) strategy to identify proteins binding to both coding and noncoding RNAs is presented.

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Regional Bone Mineral Density Differences measured by QCT: Does the Standard Clinically Used L1-L2 Average Correlate with the Entire Lumbosacral Spine?

Publication date: Available online 18 October 2018

Source: The Spine Journal

Author(s): Stephan N. Salzmann, Toshiyuki Shirahata, Jingyan Yang, Courtney Ortiz Miller, Brandon B. Carlson, Colleen Rentenberger, John A. Carrino, Jennifer Shue, Andrew A. Sama, Frank P. Cammisa, Federico P. Girardi, Alexander P. Hughes

ABSTRACT

Background context

Quantitative computed tomography (QCT) of the lumbar spine is used as an alternative to dual-energy X-ray absorptiometry in assessing bone mineral density (BMD). The average BMD of L1-L2 is the standard reportable metric used for diagnostic purposes according to current recommendations. The density of L1 and L2 has also been proposed as a reference value for the remaining lumbosacral vertebrae and is commonly used as a surrogate marker for overall bone health. Since regional BMD differences within the spine have been proposed, it is unclear if the L1-L2 average correlates with the remainder of the lumbosacral spine.

Purpose

The aims of this study were to determine possible BMD variations throughout the lumbosacral spine in patients undergoing lumbar fusion and to assess the correlation between the clinically-used L1-L2 average and the remaining lumbosacral vertebral levels.

Study Design/Setting

This is a retrospective case series.

Patient Sample

Patients undergoing posterior lumbar spinal fusion from 2014 to 2017 at a single, academic institution with available preoperative CT imaging were included in this study.

Outcome Measures

The outcome measure was BMD measured by QCT.

Methods

Standard quantitative computed tomography (QCT) measurements at the L1 and L2 vertebra and additional experimental measurements of L3, L4, L5 and S1 were performed. Subjects with missing preoperative lumbar spine CT imaging were excluded. The correlations between the L1-L2 average and the other vertebral bodies of the lumbosacral spine (L3, L4, L5, S1) were evaluated.

Results

In total, 296 consecutive patients (55.4% female, mean age of 63.1 years) with available preoperative CT were included. The vertebral BMD values showed a gradual decrease from L1 to L3 and increase from L4 to S1 (L1=118.8 mg/cm³, L2=116.6 mg/cm³, L3=112.5 mg/cm³, L4=122.4 mg/cm³, L5=135.3 mg/cm³, S1 =157.4 mg/cm³). There was strong correlation between the L1-L2 average and the average of the other lumbosacral vertebrae (L3-S1) with a Pearson's correlation coefficient (r=0.85). We also analyzed the correlation between the L1-L2 average and each individual lumbosacral vertebra. Similar relationships were observed (r value, 0.67 - 0.87), with the strongest correlation between the L1-L2 average and L3 (r=0.87).

Conclusions

Our data demonstrate regional BMD differences throughout the lumbosacral spine. Nevertheless, there is high correlation between the clinically-used L1-L2 average and the BMD values in the other lumbosacral vertebrae. We therefore conclude the standard clinically-used L1-L2 BMD average is a useful bone quantity measure of the entire lumbosacral spine in patients undergoing lumbar spinal fusion.

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Triple Combo Regimens May Address Cause of Cystic Fibrosis

FRIDAY, Oct. 19, 2018 -- Triple therapy with VX-659 or VX-445 combined with tezacaftor-ivacaftor shows promise for the treatment of adult patients with cystic fibrosis who have mutations in the cystic fibrosis transmembrane conductance regulator...

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2014 to 2016 Saw 470 Percent Increase in HIV PrEP Use in U.S.

FRIDAY, Oct. 19, 2018 -- From 2014 to 2016 there was an increase in the annual number of HIV preexposure prophylaxis (PrEP) users in the United States, although only about 7 percent of those with indications for PrEP were prescribed PrEP in 2016,...

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Light Use of Topical Skin Tx Before Radiotherapy Seems Safe

FRIDAY, Oct. 19, 2018 -- Contrary to the advice most cancer patients receive, light or moderate use of topical agents before radiation treatment does not appear to increase the radiation dose to the skin, according to a study published online Oct....

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Asthma May Raise Obesity Risk Later in Childhood

FRIDAY, Oct. 19, 2018 -- Early-onset asthma and wheezing may contribute to an increased risk of developing obesity later in childhood, according to a study published in the Sept. 1 issue of the European Respiratory Journal. Zuelma A. Contreras, from...

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Bioinformatics Tool Can ID Source of Bloodstream Pathogens

FRIDAY, Oct. 19, 2018 -- A streamlined bioinformatics tool can match bloodstream pathogens to a candidate source, according to a study published online Oct. 15 in Nature Medicine. Fiona B. Tamburini, from Stanford University in California, and...

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Aspirin, Anticoagulants Similarly Prevent VTE After TKA

FRIDAY, Oct. 19, 2018 -- Among patients undergoing total knee arthroplasty (TKA), aspirin alone may provide protection against postoperative venous thromboembolism (VTE) that is similar to that of other anticoagulants, according to a study published...

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ASA: Dorsal Root Ganglion Stimulation Disrupts Back Pain

FRIDAY, Oct. 19, 2018 -- Dorsal root ganglion (DRG) neurostimulation therapy may reduce pain and disability in patients with chronic lower extremity and back pain, according to a study presented at the annual meeting of the American Society of...

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Transcatheter Mitral Valve Repair Benefits Some With Heart Failure

FRIDAY, Oct. 19, 2018 -- Transcatheter mitral-valve repair results in a lower rate of hospitalization and lower all-cause mortality than medical therapy alone among patients with heart failure and moderate-to-severe secondary mitral regurgitation...

https://ift.tt/2EvT4Z3

Poor Experience With PCP Linked to Hospitalization in CKD

FRIDAY, Oct. 19, 2018 -- For Hispanic patients with chronic kidney disease (CKD), lower perceived quality of the patient experience with their primary care physician is associated with increased risk of hospitalization, according to a study...

https://ift.tt/2S0viXK

A New Ex Vivo Model for the Evaluation of Endoscopic Submucosal Injection Material Performance

We developed a new ex vivo model that applies constant tension to the porcine gastric specimen. This development made it possible to evaluate the performance (the height and duration of the submucosal elevation) of various SIMs accurately. The detailed setup methodology of this new model is explained.

https://ift.tt/2yrZKlw

Time-lapse 3D Imaging of Phagocytosis by Mouse Macrophages

Here we describe methods using spinning disk confocal microscopy to image single phagocytic events by mouse resident peritoneal macrophages. The protocols can be extended to other phagocytic cells.

https://ift.tt/2yMnpwr

One-year outcomes in children with eosinophilic esophagitis

Abstract

Background and aims

Despite rising incidence of eosinophilic esophagitis (EoE), data on the follow-up and treatment outcomes in pediatric patients are scarce. Therefore, the aim of this study was to present data on the treatment outcomes in children diagnosed with EoE who were treated in a tertiary medical center.

Patients and methods

A retrospective study involving patients younger than 18 years who were diagnosed with EoE in our center between January 2011 and June 2017.

Results

Thirty-two patients met inclusion criteria and were followed up for a mean of 3 years (range 0.5–6.8). Six months after the diagnosis, 28 (87.5%) children were still followed up; 21 (75%) were in clinical remission, including 10 (36%) who were in histological remission. After 12 months, 27 patients were still followed up; 21 (78%) achieved clinical remission, including 10 (37%) with histological remission. During follow-up, three patients developed gastroesophageal reflux disease (GERD). There was no difference in body mass index (BMI) Z score between baseline and 12 months follow-up (median − 0.3 vs − 0.3 SD, p = 0.862).

Conclusions

Absence of symptoms does not indicate mucosal healing; therefore, patients should be followed up endoscopically. Additionally, despite restricted diet, nutritional status remains unaffected. Finally, patients with EoE can develop significant GERD even years after the EoE diagnosis.

https://ift.tt/2ypmO46

Immunotherapy Drug Cemiplimab Approved for Advanced Squamous Cell Skin Cancer

The Food and Drug Administration approved the immunotherapy drug cemiplimab (Libtayo) for an advanced form of cutaneous squamous cell carcinoma (SCC), a common type of skin cancer. It is the first agent to be approved specifically for advanced SCC.

https://ift.tt/2Aj5M9a

Loss of GRHL3 leads to TARC/CCL17-mediated keratinocyte proliferation in the epidermis

Loss of GRHL3 leads to TARC/CCL17-mediated keratinocyte proliferation in the epidermis

Loss of <i>GRHL3</i> leads to TARC/CCL17-mediated keratinocyte proliferation in the epidermis, Published online: 19 October 2018; doi:10.1038/s41419-018-0901-6

Loss of GRHL3 leads to TARC/CCL17-mediated keratinocyte proliferation in the epidermis

https://ift.tt/2q0GBm3

miR4673 improves fitness profile of neoplastic cells by induction of autophagy

miR4673 improves fitness profile of neoplastic cells by induction of autophagy

miR4673 improves fitness profile of neoplastic cells by induction of autophagy, Published online: 19 October 2018; doi:10.1038/s41419-018-1088-6

miR4673 improves fitness profile of neoplastic cells by induction of autophagy

https://ift.tt/2NNeXSR

AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields (TTFields)

AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields (TTFields)

AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields (TTFields), Published online: 19 October 2018; doi:10.1038/s41419-018-1085-9

AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields (TTFields)

https://ift.tt/2q0Grer

Targeting enhancer of zeste homolog 2 protects against acute kidney injury

Targeting enhancer of zeste homolog 2 protects against acute kidney injury

Targeting enhancer of zeste homolog 2 protects against acute kidney injury, Published online: 19 October 2018; doi:10.1038/s41419-018-1012-0

Targeting enhancer of zeste homolog 2 protects against acute kidney injury

https://ift.tt/2NMudQ4

MicroRNA-495-3p inhibits multidrug resistance by modulating autophagy through GRP78/mTOR axis in gastric cancer

MicroRNA-495-3p inhibits multidrug resistance by modulating autophagy through GRP78/mTOR axis in gastric cancer

MicroRNA-495-3p inhibits multidrug resistance by modulating autophagy through GRP78/mTOR axis in gastric cancer, Published online: 19 October 2018; doi:10.1038/s41419-018-0950-x

MicroRNA-495-3p inhibits multidrug resistance by modulating autophagy through GRP78/mTOR axis in gastric cancer

https://ift.tt/2q8UrTD

A functional genomics screen reveals a strong synergistic effect between docetaxel and the mitotic gene DLGAP5 that is mediated by the androgen receptor

A functional genomics screen reveals a strong synergistic effect between docetaxel and the mitotic gene DLGAP5 that is mediated by the androgen receptor

A functional genomics screen reveals a strong synergistic effect between docetaxel and the mitotic gene DLGAP5 that is mediated by the androgen receptor, Published online: 19 October 2018; doi:10.1038/s41419-018-1115-7

A functional genomics screen reveals a strong synergistic effect between docetaxel and the mitotic gene DLGAP5 that is mediated by the androgen receptor

https://ift.tt/2NSEmKW

Diesel exhaust particles induce autophagy and citrullination in Normal Human Bronchial Epithelial cells

Diesel exhaust particles induce autophagy and citrullination in Normal Human Bronchial Epithelial cells

Diesel exhaust particles induce autophagy and citrullination in Normal Human Bronchial Epithelial cells, Published online: 19 October 2018; doi:10.1038/s41419-018-1111-y

Diesel exhaust particles induce autophagy and citrullination in Normal Human Bronchial Epithelial cells

https://ift.tt/2q3ein3

Activation of the interferon type I response rather than autophagy contributes to myogenesis inhibition in congenital DM1 myoblasts

Activation of the interferon type I response rather than autophagy contributes to myogenesis inhibition in congenital DM1 myoblasts

Activation of the interferon type I response rather than autophagy contributes to myogenesis inhibition in congenital DM1 myoblasts, Published online: 19 October 2018; doi:10.1038/s41419-018-1080-1

Activation of the interferon type I response rather than autophagy contributes to myogenesis inhibition in congenital DM1 myoblasts

https://ift.tt/2NQh9Jo

In Vitro and In Vivo Approaches to Determine Intestinal Epithelial Cell Permeability

Two methods are presented here to determine intestinal barrier function. An epithelial meter (volt/ohm) is used for measurements of transepithelial electrical resistance of cultured epithelia directly in tissue culture wells. In mice, the FITC-dextran gavage method is used to determine the intestinal permeability in vivo.

https://ift.tt/2CUqOxo

Age-Related Seroprevalence of Antibodies Against AAV-LK03 in a UK Population Cohort

Human Gene Therapy, Ahead of Print.

https://ift.tt/2Ct9AGp

The preload force affects the perception threshold of muscle vibration-induced movement illusions

Abstract

The control and the execution of motor tasks are largely influenced by proprioceptive feedback, i.e. the information about the position and movement of the body. In 1972, it was discovered that a vibratory stimulation applied non-invasively to a muscle or a tendon induces a movement illusion consistent with the elongation of the vibrated muscle/tendon. Although this phenomenon was reported by several studies, it is still unclear how to reliably reproduce it because of the many different features of the stimulation altering the sensation (e.g. frequency, duration, location). By performing a psychophysical test, we analysed the effects of the stimulation point and the preload force on the minimum stimulation amplitude needed to elicit an illusion of movement. In particular, we stimulated two groups of healthy subjects on three target regions of the biceps brachii muscle (the distal tendon, the muscle belly and one of the proximal tendons) applying three preload force ranges (0.5–0.75N, 1–2N and 3–4N). Our results showed that the minimum stimulation amplitude eliciting a sensation is affected by the preload force. On the contrary, it did not change significantly among the three stimulated regions. Nevertheless, the reported vividness of the illusion of movement changed across the stimulated points decreasing while moving from the distal to the proximal tendons. Overall, these outcomes contribute to the scientific debate on the features that modulate the vibration-induced movement illusion proposing ways to increase the reliability of the procedure in basic and applied research studies.

https://ift.tt/2RV2n7z

Patient, tumor, and healthcare factors associated with regional variability in lung cancer survival: a Spanish high-resolution population-based study

ABSTRACT

Purpose

The third most frequently diagnosed cancer in Europe in 2018 was lung cancer; it is also the leading cause of cancer death in Europe. We studied patient and tumor characteristics, and patterns of healthcare provision explaining regional variability in lung cancer survival in southern Spain.

Methods

A population-based cohort study included all 1196 incident first invasive primary lung cancer (C33–C34 according to ICD-10) cases diagnosed between 2010 and 2011 with follow-up until April 2015. Data were drawn from local population-based cancer registries and patients' hospital medical records from all public and private hospitals from two regions in southern Spain.

Results

There was evidence of regional differences in lung cancer late diagnosis (58% stage IV in Granada vs. 65% in Huelva, p value < 0.001). Among patients with stage I, only 67% received surgery compared with 0.6% of patients with stage IV. Patients treated with a combination of radiotherapy, chemotherapy, and surgery had a 2-year mortality risk reduction of 94% compared with patients who did not receive any treatment (excess mortality risk 0.06; 95% CI 0.02–0.16). Geographical differences in survival were observed between the two regions: 35% vs. 26% at 1-year since diagnosis.

Conclusions

The observed geographic differences in survival between regions are due in part to the late cancer diagnosis which determines the use of less effective therapeutic options. Results from our study justify the need for promoting lung cancer early detection strategies and the harmonization of the best practice in lung cancer management and treatment.

https://ift.tt/2OyCoo9

Hurricane deployment is not Beach Week for Ambulance Strike Teams

Operating in the public eye under conditions that may require evacuation or assisting colleagues at a moment's notice means responders must be ready 24/7

https://ift.tt/2OvTxz3

INT-HA induces M2-like macrophage differentiation of human monocytes via TLR4-miR-935 pathway

Abstract

As a major component of the microenvironment of solid tumors, tumor-associated macrophages (TAMs) facilitate tumor progression. Intermediate-sized hyaluronan (INT-HA) fragments have an immunological function in cell differentiation; however, their role in promoting the polarization of non-activated macrophages to an M2-like TAM phenotype has not been characterized, and the underlying mechanisms remain unclear. Here, we used a miRNA microarray to find that some miRNAs (especially miR-935) were differentially regulated in INT-HA-induced M2-like macrophages. According to RT-qPCR and Western blot, there was an association between miR-935 and C/EBPβ, that control the polarization of macrophages. Moreover, we found that INT-HA induced an M2-like phenotype via the TLR4 receptor. In our study, there was a negative correlation between plasma HA and miR-935 in monocytes from the peripheral blood of patients with solid tumors. There was also a negative correlation between miR-935 and M2-like macrophage markers in monocytes. These findings suggest that HA fragments interact with TLR4 and educate macrophage polarization to an M2-like phenotype via miR-935. Therefore, this study provides new insight into the role of miR-935 in INT-HA-induced M2-like polarization, and suggests a potential therapeutic target for antitumor treatment.

https://ift.tt/2Ex6pAj

INT-HA induces M2-like macrophage differentiation of human monocytes via TLR4-miR-935 pathway

Abstract

https://ift.tt/2Ex6pAj

Correction to: Cancer Biother Radiopharm 2014;29(8):303–309. DOI: 10.1089/cbr.2014.1653 and Cancer Biother Radiopharm 2014;29(10):451–456. DOI: 10.1089/cbr.2014.1698

Cancer Biotherapy and Radiopharmaceuticals, Volume 33, Issue 8, Page 363-363, October 2018.

https://ift.tt/2CsQ1OB

Despite the high interpatient PTV (size and position) variability, it was possible to set a standard SHL AP optimization list with a high level of generalizability. Using the implemented list, the AP module was able to limit OAR doses, producing clinically acceptable plans with stable quality without additional user input. Overall, the AP engine associated to the arc technique represents the best option for SHL.

https://ift.tt/2pYIoYK

Improving 3D-printing of megavoltage X-rays radiotherapy bolus with surface-scanner

Abstract

Background

Computed tomography (CT) data used for patient radiotherapy planning can nowadays be used to create 3D-printed boluses. Nevertheless, this methodology requires a second CT scan and planning process when immobilization masks are used in order to fit the bolus under it for treatment.

This study investigates the use of a high-grade surface-scanner to produce, prior to the planning CT scan, a 3D-printed bolus in order to increase the workflow efficiency, improve treatment quality and avoid extra radiation dose to the patient.

Methods

The scanner capabilities were tested on a phantom and on volunteers. A phantom was used to produce boluses in the orbital region either from CT data (resolution ≈1 mm), or from surface-scanner images (resolution 0.05 mm). Several 3D-printing techniques and materials were tested. To quantify which boluses fit best, they were placed on the phantom and scanned by CT. Hounsfield Unit (HU) profiles were traced perpendicular to the phantom's surface. The minimum HU in the profiles was compared to the HU values for calibrated air-gaps. Boluses were then created from surface images of volunteers to verify the feasibility of surface-scanner use in-vivo.

Results

Phantom based tests showed a better fit of boluses modeled from surface-scanner than from CT data. Maximum bolus-to-skin air gaps were 1-2 mm using CT models and always < 0.6 mm using surface-scanner models. Tests on volunteers showed good and comfortable fit of boluses produced from surface-scanner images acquired in 0.6 to 7 min. Even in complex surface regions of the body such as ears and fingers, the high-resolution surface-scanner was able to acquire good models. A breast bolus model generated from images acquired in deep inspiration breath hold was also successful. None of the 3D-printed bolus using surface-scanner models required enlarging or shrinking of the initial model acquired in-vivo.

Conclusions

Regardless of the material or printing technique, 3D-printed boluses created from high-resolution surface-scanner images proved to be superior in fitting compared to boluses created from CT data. Tests on volunteers were promising, indicating the possibility to improve overall radiotherapy treatments, primarily for megavoltage X-rays, using bolus modeled from a high-resolution surface-scanner even in regions of complex surface anatomy.

https://ift.tt/2NRmPTH

Stereotactic ablative radiotherapy (SABR) as primary, adjuvant, consolidation and re-treatment option in pancreatic cancer: scope for dose escalation and lessons for toxicity

Abstract

Background

Stereotactic ablative radiotherapy (SABR) offers an alternative treatment for pancreatic cancer, with the potential for improved tumour control and reduced toxicity compared with conventional therapies. However, optimal dose planning and delivery strategies are unelucidated and gastro-intestinal (GI) toxicity remains a key concern.

Methods

Patients with inoperable non-metastatic pancreatic cancer who received CyberKnife® SABR (18–36 Gy) in three fractions as primary, adjuvant, consolidation or re-treatment options were studied. Patient individualised planning and delivery variables were collected and their impact on patient outcome examined. Linear-quadratic (LQ) radiobiology modelling methods were applied to assess SABR parameters against a conventional fractionated radiotherapy schedule.

Results

In total 42 patients were included, 37 (88%) of whom had stage T4 disease. SABR was used > 6 months post-primary therapy to re-treat residual disease in 11 (26.2%) patients and relapsed disease in nine (21.4%) patients. SABR was an adjuvant to other primary therapy for 14 (33.3%) patients and was the sole primary therapy for eight (19.0%) patients. The mean (95% CI) planning target volume (PTV), prescription isodose, percentage cover, minimum dose to PTV and biological effective dose (BED) were 76.3(63.8–88.7) cc, 67.3(65.2–69.5)%, 96.6(95.5–97.7)%, 22.3(21.0–23.6) Gy and 50.3(47.7–53.0) Gy, respectively. Only 3/37 (8.1%) patients experienced Grade 3 acute toxicities. Two (4.8%) patients converted to resectable status and median freedom-from-local-progression (FFLP) and overall survival (OS) were 9.8 and 8.4 months, respectively. No late toxicity was experienced in 27/32 (84.4%) patients; however, four (12.5%) patients — of whom two had particularly large PTV, two had sub-optimal number of fiducials and three breached organ-at-risk (OAR) constraints—showed Grade 4 duodenal toxicities. Longer delivery time, extended treatment course and reduced percentage coverage additionally associated with late toxicity, likely reflecting parameters typically applied to riskier patients. Larger PTV size and longer treatment course associated with OS. Comparator regimen LQ modelling analysis indicated 50% of patients received minimum PTV doses less potent than a conventional radiotherapy regimen, indicating scope for dose escalation.

Conclusion

The results demonstrate the value of SABR for a range of indications in pancreatic cancer. Dose escalation to increase BED may improve FFLP and OS in inoperable, non-metastatic disease: however concomitant enhanced stringency for duodenal protection is critical, particularly for patients where SABR is more challenging.

https://ift.tt/2q2iPWO

Organic Photo‐Electrochemical Transistor‐Based Biosensor: A Proof‐of‐Concept Study toward Highly Sensitive DNA Detection

Advanced Healthcare Materials, Volume 7, Issue 19, October 10, 2018.

https://ift.tt/2MSYiOi

New Research From Clinical Psychological Science

Read about the latest research published in Clinical Psychological Science:

Involuntary Autobiographical Memory and Future Thought Predicting Hallucination Proneness
Mélissa C. Allé, Fabrice Berna, and Dorthe Berntsen

Allé and colleagues conducted two studies using validated scales to test the relationship between the frequency of involuntary autobiographical memories and future thoughts (i.e., imagination of possible future events) and hallucination proneness. In Study 1, they asked participants to rate whether their involuntary memories and thoughts were positive or negative and how intense they were. In Study 2, the researchers included additional measures of personality, depression, dissociation, executive functions, and imagery abilities. Results indicated that participants who experienced more frequent and emotionally intense involuntary memories and future thoughts were more prone to hallucination. This relationship was not altered by the valence of the memories and thoughts, and persisted even when unwanted thought suppression, rumination, depression, dissociation, executive functions, imagery abilities, and personality variables were controlled for. These findings suggest a role of involuntary autobiographical memories and future thoughts in relation to hallucinations and, possibly, psychosis.

Psychopathy and Ratings of Persuasiveness: Examining Their Relations in Weaker and Stronger Contexts
Brandon M. Weiss, Donald R. Lynam, Joshua D. Miller

Boldness – resilience to stress, fearlessness, and social influence – may be relevant to psychopathy, specifically by enhancing an individual's persuasiveness. To explore this possible relationship, Weiss and colleagues asked participants to complete measures of psychopathy, personality, and cognitive ability; to measure persuasiveness, they also asked participants to video record themselves either improvising a persuasive product pitch or reading a script for a persuasive product pitch. Independent raters coded the videos for persuasiveness and trustworthiness. The results indicated that high persuasiveness ratings were associated with extraversion, high IQ, high attractiveness, and high trustworthiness. Moreover, boldness predicted persuasiveness, but only in the improvised condition. These results suggest that boldness may enhance one's ability to persuade and manipulate others and could play a role in psychopathy-related behaviors.

Making Decisions With Trees: Examining Marijuana Outcomes Among College Students Using Recursive Partitioning
Adam D. Wilson, Kevin S. Montes, Adrian J. Bravo, Bradley T. Conner, Matthew R. Pearson, and the Marijuana Outcomes Study Team

Decision tree learning is a type of machine learning that allows users to develop predictive models from data. Wilson and colleagues used this type of modeling to predict relative risk and outcomes of marijuana use among college students at 11 different universities. The researchers found that the strongest predictors of having used marijuana at least once were (a) perceived approval of best friends and others and (b) internalization of college marijuana-use culture. The strongest predictors of past-month use were (a) identifying as a marijuana user, (b) perceptions of others' approval, and (c) perceptions of others' marijuana use. Negative consequences were mostly correlated with frequency of marijuana use and the tendency to act rashly in response to strong emotions. Employing strategies to reduce use, intoxication, and harm of marijuana use was a protective factor against these negative consequences. These results indicate that social norms are an especially important contributor to marijuana use among college students and that tree-based modeling might be a useful methodology to identify targets for future clinical research.

https://ift.tt/2OynVsw

Synchronized Ratiometric Codelivery of Metformin and Topotecan through Engineered Nanocarrier Facilitates In Vivo Synergistic Precision Levels at Tumor Site

Advanced Healthcare Materials, Volume 7, Issue 19, October 10, 2018.

https://ift.tt/2Owd91t

Peptide–Gold Nanoparticle Hybrids as Promising Anti‐Inflammatory Nanotherapeutics for Acute Lung Injury: In Vivo Efficacy, Biodistribution, and Clearance

Advanced Healthcare Materials, Volume 7, Issue 19, October 10, 2018.

https://ift.tt/2vEUWHQ

Renal Tubular‐ and Vascular Basement Membranes and their Mimicry in Engineering Vascularized Kidney Tubules

Advanced Healthcare Materials, Volume 7, Issue 19, October 10, 2018.

https://ift.tt/2vJUect

Human Corneal Tissue Model for Nociceptive Assessments

Advanced Healthcare Materials, Volume 7, Issue 19, October 10, 2018.

https://ift.tt/2Owd7GT

Embryonic‐Like Mineralized Extracellular Matrix/Stem Cell Microspheroids as a Bone Graft Substitute

Advanced Healthcare Materials, Volume 7, Issue 19, October 10, 2018.

https://ift.tt/2OSZEdm

HIF-2α promotes conversion to a stem cell phenotype and induces chemoresistance in breast cancer cells by activating Wnt and Notch pathways

Abstract

Background

Hypoxic tumor microenvironment and maintenance of stemness contribute to drug resistance in breast cancer. However, whether Hypoxia-inducible factor-2α (HIF-2α) in hypoxic tumor microenvironment mediates conversion to a stem cell phenotype and chemoresistance of breast tumors has not been elucidated.

Methods

The mRNA and protein expressions of HIF-1α, HIF-2α, Wnt and Notch pathway were determined using qRT-PCR and western blot. Cell viability and renew ability were assessed by MTT, Flow cytometric analysis and soft agar colony formation.

Results

In our study, acute hypoxia (6–12 h) briefly increased HIF-1α expression, while chronic hypoxia (48 h) continuously enhanced HIF-2α expression and induced the resistance of breast cancer cells to Paclitaxel (PTX). Furthermore, HIF-2α overexpression induced a stem cell phenotype, the resistance to PTX and enhanced protein expression of stem cell markers, c-Myc, OCT4 and Nanog. Most importantly, Wnt and Notch signaling, but not including Shh, pathways were both activated by HIF-2α overexpression. Dickkopf-1 (DKK-1), a Wnt pathway inhibitor, and L685,458, an inhibitor of the Notch pathway, reversed the resistance to PTX and stem phenotype conversion induced by HIF-2α overexpression. In addition, HIF-2α overexpression enhanced tumorigenicity and resistance of xenograft tumors to PTX, increased activation of the Wnt and Notch pathways and induced a stem cell phenotype in vivo.

Conclusion

In conclusion, HIF-2α promoted stem phenotype conversion and induced resistance to PTX by activating Wnt and Notch pathways.

https://ift.tt/2PJzWbg

Identification of a novel host protein interacting with Toxoplasma gondii toxofilin via a yeast two-hybrid system

https://ift.tt/2AknhpX

CC chemokine ligand 2 (CCL2) enhances TTX-sensitive sodium channel activity of primary afferent neurons in the complete Freud adjuvant-induced inflammatory pain model

Abstract

CC chemokine ligand 2 (CCL2) has been implicated in pathological pain, but the mechanism underlying the pronociceptive effect of CCL2 is not fully understood. Voltage-gated sodium (Nav) channels are important determinants of the excitability of sensory neurons. Hence we tested the hypothesis that CCL2 contributes to inflammatory pain via modulating Nav channel activity of primary afferent neurons. Chronic inflammatory pain was induced in rats by intraplantar injection of the complete Freud adjuvant (CFA) to one of the hind paws. Control rats received intraplantar injection of equal volume of saline. A significant increase of CCL2 mRNA and CCL2 receptor (CCR2) protein expression was detected in the ipsilateral dorsal root ganglion (DRG) in CFA-treated rats. Intraplantar injection of CCL2 protein in the control rats had minimal effect on the paw withdrawal threshold (PWT) in response to mechanical stimulation. However, in CFA-treated rats, intraplantar CCL2 led to an increase in pain responses. Patch-clamp recording of acutely dissociated DRG neurons revealed that CCL2 had minimum effect on the excitability of sensory neurons from control rats. However, CCL2 directly depolarized a large proportion of small to medium-sized sensory neurons from CFA-treated rats. In addition, CCL2 was found to enhance whole-cell TTX-sensitive sodium currents without significantly affecting the TTX-resistant sodium currents and the potassium currents. These results are in agreement with previous reports concerning the involvement of CCL2–CCR2 signaling in inflammatory hyperalgesia and further indicate that enhanced TTX-sensitive channel activity may partly underlie the pronociceptive effects of CCL2.

https://ift.tt/2R6J7mr

FSTL1 enhances chemoresistance and maintains stemness in breast cancer cells via integrin β3/Wnt signaling under miR-137 regulation

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https://ift.tt/2NMTdqt

Alpha inhibitory processes reflect motor stimuli by either increasing or decreasing amplitude (i.e., power). However, the functional role and interplay of event-related alpha oscillations remains a regulatory domain that has not been sufficiently addressed, particularly with respect to different muscle activation types and durations in consecutive movement (i.e., motor) tasks. The aim of this study was to investigate alpha-band activity (7–13 Hz) in longer vs. shorter timed isometric muscle activations at distinct torques (20% and 40% of maximum voluntary contraction, MVC) when combined in one motor task sequence. In a randomized and controlled design, 18 healthy males volunteered to perform 40 longer (i.e., 6 s) and 40 shorter (i.e., 3 s) motor task sequences, each comprising isometric contractions (i.e., palmar flexion) from baseline to 20% and 40% MVC subsequent to relaxations from 40% and 20% MVC to baseline. Continuous, synchronized EEG, EMG and torque recordings served to determine alpha-band activity over task-relevant motor areas at distinct torques. Main findings revealed increases in alpha activity during subsequent progressive muscle relaxation (from 20% MVC in long and short: p < .001; from 40% MVC in short: p < .05), whereas modulations in relevant motor areas were not significant (p = .84). It may be suggested that an active task-relevant inhibitory process indicates motor task sequence-related relaxation mirrored by an increasing alpha activity.

https://ift.tt/2PILyeD

VX-659–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles

New England Journal of Medicine, Ahead of Print.

https://ift.tt/2EvPKgp

Triple CFTR Modulator Therapy for Cystic Fibrosis

New England Journal of Medicine, Ahead of Print.

https://ift.tt/2RYok5L

VX-445–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles

New England Journal of Medicine, Ahead of Print.

https://ift.tt/2EuEoJH

PERIPROSTHETIC FEMORAL NONUNIONS TREATED WITH INTERNAL FIXATION AND BONE GRAFTING

Publication date: Available online 18 October 2018

Source: Injury

Author(s): Jonne Prins, Johanna C.E. Donders, David L. Helfet, David S. Wellman, Craig E. Klinger, Mariya Redko, Peter Kloen

Abstract

Introduction

Periprosthetic femoral nonunions (PPFN) have a reported incidence of 3-9%. Literature on PPFN management is scarce. The study aim was to review combined results of two academic teaching hospitals using comparable PPFN treatment strategies.

Materials and Methods

A retrospective review was conducted of all patients treated for a PPFN between February 2005 and December 2016. All patients treated with internal fixation for a PPFN with complete clinical and radiological follow-up until healing were included. Nineteen patients were identified (mean age 71.2 years, range 49-87). Treatment consisted of failed hardware removal, debridement, reduction, and rigid internal fixation with or without bone graft. For revision PPFN surgery, use of dual-plating and bone graft augmentation was common.

Results

Eighteen of 19 patients (94.7%) progressed to osseous union. One patient was converted to a total femoral prosthesis. No patients were lost to follow-up. All were ambulatory at last follow-up and mean follow-up was 39.8 months. Fourteen patients (73.7%) united after our index nonunion surgery at mean 9.8 months. Five patients (26.3%) required revision surgery after our index nonunion treatment and in 4 of these cases union was achieved at mean 18.0 months.

Conclusions

Our results suggest debridement, revision of fixation and liberal use of bone grafting can lead to reliable healing in the majority of PPFNs. For those PPFNs that do not heal following initial treatment, good healing potential persists with an additional procedure.

Level of Evidence

Prognostic Level III.

https://ift.tt/2J6WL67

CSF TACI and BAFF levels in patients with primary CNS lymphoma as novel diagnostic biomarkers

Annals of Clinical and Translational Neurology, EarlyView.

https://ift.tt/2NOP5WF

Treatment Patterns by EGFR Mutation Status in Non-Small Cell Lung Cancer Patients in the USA: A Retrospective Database Analysis

Abstract

Scalable Production of Therapeutic Protein Nanoparticles Using Flash Nanoprecipitation

Advanced Healthcare Materials, EarlyView.

https://ift.tt/2R1xgWn

Micropatterned Scaffolds with Immobilized Growth Factor Genes Regenerate Bone and Periodontal Ligament‐Like Tissues

Advanced Healthcare Materials, EarlyView.

https://ift.tt/2Aj5ake

Metal‐Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics

Advanced Healthcare Materials, EarlyView.

https://ift.tt/2R1xaxZ

VX-659–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles

New England Journal of Medicine, Ahead of Print.

https://ift.tt/2EvPKgp

Triple CFTR Modulator Therapy for Cystic Fibrosis

New England Journal of Medicine, Ahead of Print.

https://ift.tt/2RYok5L

VX-445–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles

New England Journal of Medicine, Ahead of Print.

https://ift.tt/2EuEoJH

Ultrathin Ti2Nb2O9 Nanosheets with Pseudocapacitive Properties as Superior Anode for Sodium‐Ion Batteries

Advanced Materials, EarlyView.

https://ift.tt/2pZGbMA

Regulatory Aspects of the Development of Drugs for Metabolic Bone Diseases – FDA and EMA Perspective

British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.

https://ift.tt/2J68MZE

Effect of chlorogenic acids on fatigue and sleep in healthy males: A randomized, double‐blind, placebo‐controlled, crossover study

Food Science &Nutrition, EarlyView.

https://ift.tt/2P900PQ

The effect of traditional malting technology practiced by an ethnic community in northern Uganda on in‐vitro nutrient bioavailability and consumer sensory preference for locally formulated complementary food formulae

Food Science &Nutrition, EarlyView.

https://ift.tt/2PJo3lu

Efficacy of a survivorship‐focused consultation versus a time‐controlled rehabilitation consultation in patients with lymphoma: a cluster randomized controlled trial

Cancer, EarlyView.

https://ift.tt/2RYEWKm

Reply to Are adjuvant radiotherapy outcomes really better in patients with early‐stage oral cavity squamous cell carcinoma?

Cancer, EarlyView.

https://ift.tt/2S6l34m

Value of contrast‐enhanced harmonic EUS with enhancement pattern for diagnosis of pancreatic cancer: a meta‐analysis

Digestive Endoscopy, Volume 0, Issue ja, -Not available-.

https://ift.tt/2NPwI3W

Caring for Critically Ill Patients with the ABCDEF Bundle: Results of the ICU Liberation Collaborative in Over 15,000 Adults

Objective: Decades-old, common ICU practices including deep sedation, immobilization, and limited family access are being challenged. We endeavoured to evaluate the relationship between ABCDEF bundle performance and patient-centered outcomes in critical care. Design: Prospective, multicenter, cohort study from a national quality improvement collaborative. Setting: 68 academic, community, and federal ICUs collected data during a 20-month period. Patients: 15,226 adults with at least one ICU day. Interventions: We defined ABCDEF bundle performance (our main exposure) in two ways: 1) complete performance (patient received every eligible bundle element on any given day) and 2) proportional performance (percentage of eligible bundle elements performed on any given day). We explored the association between complete and proportional ABCDEF bundle performance and three sets of outcomes: patient-related (mortality, ICU and hospital discharge), symptom-related (mechanical ventilation, coma, delirium, pain, restraint use), and system-related (ICU readmission, discharge destination). All models were adjusted for a minimum of 18 a priori determined potential confounders. Measurements and Results: Complete ABCDEF bundle performance was associated with lower likelihood of seven outcomes: hospital death within 7 days (adjusted hazard ratio, 0.32; CI, 0.17–0.62), next-day mechanical ventilation (adjusted odds ratio [AOR], 0.28; CI, 0.22–0.36), coma (AOR, 0.35; CI, 0.22–0.56), delirium (AOR, 0.60; CI, 0.49–0.72), physical restraint use (AOR, 0.37; CI, 0.30–0.46), ICU readmission (AOR, 0.54; CI, 0.37–0.79), and discharge to a facility other than home (AOR, 0.64; CI, 0.51–0.80). There was a consistent dose-response relationship between higher proportional bundle performance and improvements in each of the above-mentioned clinical outcomes (all p

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Dihydroartemisinin induces apoptosis and inhibits proliferation, migration, and invasion in epithelial ovarian cancer via inhibition of the hedgehog signaling pathway

Cancer Medicine, EarlyView.

https://ift.tt/2PE0ASQ

Adherence to postresection colorectal cancer surveillance at National Cancer Institute‐designated Comprehensive Cancer Centers

Cancer Medicine, EarlyView.

https://ift.tt/2Pddwlq

Cerebral small vessel disease and systemic arteriopathy in intracranial arterial dolichoectasia patients

Acta Neurologica Scandinavica, Volume 0, Issue ja, -Not available-.

https://ift.tt/2yohMoC

The inferior gluteal nerve often has a cutaneous branch: A discovery with application to hip surgery and targeting gluteal pain syndromes

Clinical Anatomy, EarlyView.

https://ift.tt/2yJn9OC

2018 Academic Emergency Medicine Consensus Conference: A Workforce Development Research Agenda for Pediatric Care in the Emergency Department

Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.

https://ift.tt/2CQaTAx

Uncovering cynicism in medical training: a qualitative analysis of medical online discussion forums

Objective

The development of cynicism in medicine, defined as a decline in empathy and emotional neutralisation during medical training, is a significant concern for medical educators. We sought to use online medical student discussion groups to provide insight into how cynicism in medicine is perceived, the consequences of cynicism on medical trainee development and potential links between the hidden curriculum and cynicism.

Setting

Online analysis of discussion topics in Premed101 (Canadian) and Student Doctor Network (American) forums.

Participants

511 posts from seven discussion topics were analysed using NVivo 11. Participants in the forums included medical students, residents and practising physicians.

Methods

Inductive content analysis was used to develop a data-driven coding scheme that evolved throughout the analysis. Measures were taken to ensure the trustworthiness of findings, including duplicate independent coding of a sub-sample of posts and the maintenance of an audit trail.

Results

Medical students, residents and practising physicians participating in the discussion forums engaged in discourse about cynicism and highlighted themes of the hidden curriculum resulting in cynicism. These included the progression of cynicism over the course of medical training as a coping mechanism; the development of challenging work environments due to factors such as limited support, hierarchical demands and long work hours; and the challenge of initiating change due to the tolerance of unprofessionalism and the highly stressful nature of medicine.

Conclusion

Our unique study of North American medical discussion posts demonstrates that cynicism develops progressively and is compounded by conflicts between the hidden and formal curriculum. Online discussion groups are a novel resource to provide insight into the culture of medical training.

https://ift.tt/2AhVy97

Arrabidaea chica for oral mucositis in patients with head and neck cancer: a protocol of a randomised clinical trial

Introduction

Oral mucositis is an iatrogenic condition of erythematous inflammatory changes which tends to occur on buccal and labial surfaces, the ventral surface of the tongue, the floor of the mouth and the soft palate of patients receiving chemotherapy. This protocol of ongoing randomised parallel group clinical trial aims to access the therapeutic effect of an herbal gel containing 2.5% Arrabidaea chica Verlot standardised extract on oral mucositis in patients with head and neck cancer compared with low-level laser therapy.

Methods and analysis

Patients with head and neck cancer held at Clinics Hospital of University of Campinas, Sao Paulo, who develop early signs/symptoms of oral mucositis are eligible. Baseline characteristics of participants include oral mucositis grade and quality of life assessments. Enrolment started in November 2017 with allocation of patients to one of the study groups by means of randomisation. Patients will be treated either with Arrabidaea chica or laser until wound healing. Monitoring includes daily assessment of mucositis grade and diameter measurement by photographs and millimetre periodontal probe. Treatments will be concluded once mucositis is healed. A blinded assessor will evaluate mucositis cure after referred by the study team. At this point, the gel tube will be weighed to indirectly assess patient's compliance. At close-out, data will be analysed by a blinded researcher following the procedures described in the statistical analyses.

Ethics and dissemination

This clinical trial was approved by the ethics committee of research in humans at the Faculty of Medical Sciences of University of Campinas (report no. 1,613,563/2016). Results from this trial will be communicated in peer-reviewed publications and scientific presentations.

Trial registration number

RBR-5x4397.

https://ift.tt/2R2VoZ3

Αρχειοθήκη ιστολογίου

Αναζήτηση αυτού του ιστολογίου

Παρασκευή 19 Οκτωβρίου 2018

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