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Πέμπτη 6 Ιουλίου 2017

Carboplatin plus weekly nanoparticle albumin-bound paclitaxel in elderly patients with previously untreated advanced squamous non-small-cell lung cancer selected based on Mini Nutritional Assessment short-form scores: a multicenter phase 2 study

Abstract

Purpose

This multicenter, single-arm, open-label, phase 2 study assessed the efficacy and safety of carboplatin plus weekly nanoparticle albumin-bound paclitaxel in elderly patients with previously untreated advanced squamous non-small-cell lung cancer, selected based on the Mini Nutritional Assessment short-form scores (MNA-SF).

Methods

Patients received carboplatin (area under the curve: 6) on Day 1, and nanoparticle albumin-bound paclitaxel (100 mg/m2) on Days 1, 8, and 15, every 28 days for ≤4 cycles. Eligibility criteria included an MNA-SF score of ≥8 points. The primary endpoint was the objective response rate.

Results

Thirty patients with a median age of 76 (range 70–83) years were enrolled. The objective response rate was 50.0% (95% confidence interval: 31.3–68.7%), which met the primary objective of this study. The disease control rate was 73.3% (95% CI: 54.1–87.7%). At a median follow-up of 15.0 months, the median progression-free and overall survival was 7.1 and 19.1 months, respectively. The most common treatment-related adverse event of Grade ≥3 was neutropenia (66.7%). Non-hematological adverse events of Grade ≥3 were minor. Well-nourished patients, based on the MNA-SF, experienced fewer adverse events of Grade ≥3 compared to patients at risk of malnutrition. All treatment-related adverse events were tolerable and reversible. There were no treatment-related deaths.

Conclusions

Carboplatin plus weekly nanoparticle albumin-bound paclitaxel is effective and well tolerated as a first-line treatment for elderly patients with advanced squamous non-small-cell lung cancer. Eligibility based on MNA-SF screening may be useful in determining acceptable toxicity.



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Optimal Measurement Interval for Emergency Department Crowding Estimation Tools

Emergency department (ED) crowding is a barrier to timely care. Several crowding estimation tools have been developed to facilitate early identification of and intervention for crowding. Nevertheless, the ideal frequency is unclear for measuring ED crowding by using these tools. Short intervals may be resource intensive, whereas long ones may not be suitable for early identification. Therefore, we aim to assess whether outcomes vary by measurement interval for 4 crowding estimation tools.

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Is Antiplatelet Therapy an Independent Risk Factor for Traumatic Intracranial Hemorrhage in Patients With Mild Traumatic Brain Injury?

A total of 3,193 separate articles were identified by the searches; 28 were selected for closer review and 10 articles were included in the final review, 1 retrospective case-control study, 7 retrospective cohort studies, and 2 prospective cohort studies, all from January 2003 to September 2015. Pooled data resulted in 2,966 patients with 553 traumatic intracranial hemorrhages (19%) in the combined antiplatelet group and 18,281 total patients with 1,422 (8%) traumatic intracranial hemorrhages in the combined control group.

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Do Corticosteroids Improve Mortality or Shock Reversal in Patients With Septic Shock?

Authors included 22 studies in the network meta-analysis, excluding 11 from the 2015 Cochrane review. Hydrocortisone infusion demonstrated superior shock reversal compared with placebo (OR 3.68; 95% CI 1.52 to 8.93) (Table). Methylprednisolone bolus was less likely to reverse shock than hydrocortisone bolus (OR 0.37; 95% CI 0.19 to 0.72). No regimens demonstrated superiority for the outcomes of mortality at 28 days, hospital mortality, ICU mortality, or incidence of superinfection. Methylprednisolone use trended toward increased mortality compared with dexamethasone (OR 5.71; 95% CI 0.99 to 32.9).

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Skin eruption and long-lasting fever in a young man

Description

A 20-year-old man presented to emergency room with a 3-week history of general weakness, fever, diffuse arthralgia and skin eruption. His medical history was unremarkable; he did not travel recently, had no contact with an ill person, nor had risky sexual behaviour and took no medication. Physical examination only showed a diffuse, non-painful, infracentimetric and non-confluent macular eruption over the trunks and limbs (figures 1 and 2). Blood test showed elevated C reactive protein and neutrophilic leucocytosis. Serologies for hepatitis C and B viruses, rubella, Epstein-Barr virus, cytomegalovirus, toxoplasmosis and HIV were negative. Urinalysis and chest X-ray were normal. Blood cultures became positive for Neisseria meningitidis, whereas skin biopsy only showed a dermic inflammatory polymorphic (lymphocytic and neutrophilic) infiltrate without specificity with negative aerobic and anaerobic cultures.

Figure 1

Macular lesions on the trunk.

Figure 2

Macular lesions...



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Diencephalic syndrome: a rare cause of failure to thrive

Timely diagnosis of diencephalic syndrome is not often the case for patients presenting with failure to thrive (FTT) because of its rarity and lack of specific symptoms. Herein, we report two cases of diencephalic syndrome (2-year-old girl and 10-month-old boy) presenting with severe emaciation. Both patients had histories of poor weight gain for months despite having good appetites prior to diagnosis. Initial work-up did not reveal the diagnosis. Horizontal nystagmus was noted in both patients: by a neurologist in the first patient and by a family member in the second patient. MRI of the brain showed large suprasellar mass and pilocytic astrocytoma was confirmed by pathology in each case. The patients were started on appropriate chemotherapy with interval improvements in weight gain. These cases illustrate the importance of cranial imaging and consideration of diencephalic syndrome for children presenting with FTT despite normal or increased caloric intake.



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Substantial harm associated with failure of chronic paediatric central venous access devices

Central venous access devices (CVADs) form an important component of modern paediatric healthcare, especially for children with chronic health conditions such as cancer or gastrointestinal disorders. However device failure and complications rates are high.

Over 21/2 years, a child requiring parenteral nutrition and associated vascular access dependency due to 'short gut syndrome' (intestinal failure secondary to gastroschisis and resultant significant bowel resection) had ten CVADs inserted, with ninesubsequently failing. This resulted in multiple anaesthetics, invasive procedures, injuries, vascular depletion, interrupted nutrition, delayed treatment and substantial healthcare costs. A conservative estimate of the institutional costs for each insertion, or rewiring, of her tunnelled CVAD was $A10 253 (2016 Australian dollars).

These complications and device failures had significant negative impact on the child and her family. Considering the commonality of conditions requiring prolonged vascular access, these failures also have a significant impact on international health service costs.



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Renal keratinising desquamative squamous metaplasia: all that hurts is not stone

Description

A 66-year-old Caucasian man with history of hypertension, hyperlipidaemia and 16 pack-year smoking was referred to us for evaluation of recurrent right-sided flank pain and suspected nephrolithiasis. His first episode of pain was 2 years prior to presentation, which was recurrent. There was no associated haematuria, dysuria, fever, chills, urinary hesitancy or incontinence. There was no family history of stones. He underwent multiple ureteroscopies, which have shown glistening, soft, acellular debris in the upper ureter. Last ureteroscopy and pyeloscopy showed normal underlying mucosa, renal pelvis and calyces with no evidence of malignancy. Subsequent MRI also did not show any malignancy. The last available pathology showed minute fragments of acellular keratin debris. Interestingly, he never had imaging evidence of renal stone, although had mild hydronephrosis one time. CT urogram demonstrated an ill-defined filling defect in the anterior right renal pelvis measuring approximately 13x3 mm in axial dimensions (figure 1). During...



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Transient neonatal hypercalcaemia secondary to excess maternal vitamin D intake: too much of a good thing

We report a case of transient neonatal hypercalcaemia secondary to excess maternal vitamin D intake in pregnancy. Vitamin D insufficiency and deficiency in pregnancy are associated with adverse pregnancy outcomes, but there is no definite benefit to supplementation. The Royal College of Obstetrics and Gynaecology recommends routine supplementation with vitamin D3 400 IU/day, but higher dose preparations usually recommended for the treatment of vitamin D deficiency are readily available over the counter. This case highlights the risks of excess supplementation, especially at higher doses and in women without evidence of vitamin D deficiency. The amount used in this case was at the upper end of the generally accepted safe dose range, but still less than that commonly recognised to cause problems. Neonatal hypercalcaemia is a potentially serious condition. The current local or national recommendations for vitamin D supplementation and the possible adverse effects of excess vitamin D consumption should be clearly communicated to pregnant women.



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Intraparenchymal pericatheter cyst in ventriculoperitoneal shunt failure

Description

A 60-year-old man status post right parieto-occipital ventriculoperitoneal shunt with programmable valve for indication of delayed hydrocephalus after aneurysmal subarachnoid haemorrhage returns to clinic 7 weeks after placement for insidious onset of headaches, confusion and gait imbalance. CT scan of the head without contrast revealed an intraparenchymal pericatheter cystic collection with severe oedema (figure 1). The patient denied systemic signs of illness, and laboratory markers for infection were low. A tap of the shunt reservoir revealed no spontaneous flow and difficulty in aspirating cerebrospinal fluid (CSF). Laboratory analysis of the fluid showed negative Gram stain, normal chemistry profile and cell counts. MRI of the brain showed a simple cyst with significant oedema, but no restricted diffusion or contrast enhancement of the cyst wall (figures 2 and 3). CT of the abdomen was benign, without evidence of pseudocyst or other cause of distal obstruction.

...



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Sternoclavicular joint osteophytosis: a difficult diagnosis to swallow

Unexplained dysphagia requires prompt investigation to rule out a possible underlying malignancy. We describe the case of a 60-year-old man who presented to his family practitioner with a 1-year history of increasing dysphagia with associated pain over the front of his chest. He was referred on to an ear, nose and throat specialist where no obvious laryngeal pathology was found at direct laryngoscopy, but an 'indentation' of the right anterior larynx, which increased with external pressure on the sternoclavicular joint (SCJ), was noted. A subsequent CT scan of his neck demonstrated osteoarthritis of the right SCJ with an abnormally large posterior osteophyte. The patient was subsequently referred on to an orthopaedic surgeon specialising in SCJ surgery and underwent an arthroscopic excision of his right SCJ. Soon after surgery, the patient's dysphagia had settled and his symptoms remain resolved 1 year post surgery.



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Cupping at the ends of ribs is not always rickets

Description

A 7-week-old baby boy presented with a history of cough, loose stools and respiratory distress since last 7 days. At admission he had a respiratory rate of 64/min, a heart rate of 144/min and an oxygen saturation of 56%. Chest examination revealed crepitations in both lung fields. Rest of the examination was unremarkable. Investigations revealed haemoglobin 82 g/L; white cell count 11.2x109/L (differential counts: polymorphs 68%, lymphocytes 1%, monocytes 26% and eosinophils 5%); absolute lymphocyte count 0.11x109/L; platelet count 102x109/L and C reactive protein 239 g/L. Chest X-ray showed non-homogenous opacities in bilateral lung fields (more on right side) with an absent thymic shadow, cupping at the anterior end of ribs (black arrow, figure 1), flattening of lower end of the right scapula (white arrow, figure 1) and a spur at the inferior-lateral angle of the left scapula (white arrow head, figure 1). These characteristic radiological changes (ie, cupping at...



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Isolated insulin-derived amyloidoma of the breast

Isolated amyloidomas derived from insulin are extremely rare, and there is only one reported case to date of insulin-derived amyloidoma in the breast.

We present the case of a 36-year-old woman reporting a lump in the right breast. It was clinically assessed as a probable fibroadenoma but was removed surgically given the size of the lesion. On histological analysis, the lesion had features consistent with amyloid. Further investigations showed the amyloid to be derived from insulin. The lump was removed in its entirety, and the patient made a full recovery.



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Bilateral interstitial keratitis with anterior stromal infiltrates associated with reactive arthritis

A previously healthy 48-year-old man presented with a 1-week history of migrating polyarthropathy preceded by a viral illness, dysuria and bilateral red eyes. Ocular examination revealed anterior and interstitial stromal keratitis. He was systemically well but had raised erythrocyte sedimentation rate and C reactive protein and was positive for human leucocyte antigen B27 on extensive infective, rheumatological and autoimmune investigations. Although the exact triggering pathogen was not identified, clinical findings were consistent with reactive arthritis. Bilateral interstitial keratitis is a rare manifestation of reactive arthritis which, along with the anterior stromal keratitis, responded well to topical prednisolone sodium phosphate 0.5%. Systemic joint symptoms improved on oral sulfasalazine, non-steroid anti-inflammatory agent and low-dose prednisolone.



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Use of low-dose thrombolytics for treatment of intracardiac thrombus and massive pulmonary embolus after aborted liver transplant leads to recovery of right ventricular function and redo liver transplantation

This is a 61-year-old man with end-stage liver disease who experienced cardiac arrest secondary to a massive pulmonary embolus and intracardiac thrombus during cannulation for veno-venous extracorporeal membrane oxygenation (ECMO) in preparation for orthotopic liver transplantation (OLT). Surgery was aborted and the patient was taken back to the intensive care unit in cardiogenic shock on multiple vasopressors. The patient was unresponsive to heparin bolus and too high risk for systemic thrombolytics or embolectomy. He was ultimately treated with 12 mg total of alteplase through his pulmonary artery catheter over 3 hours. He had subsequent resolution of his cardiogenic shock and proceeded with successful liver transplantation 5 days after his initial event without any bleeding complications. Low-dose thrombolytic therapy in the setting of absolute contraindications to thrombolysis allowed for recovery of cardiac function and, ultimately redo OLT in a patient with otherwise little hope of survival.



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Adrenal crisis in metastatic breast cancer

A female patient with oestrogen receptor-positive and human epidermal growth factor receptor 2 (HER2)-positive invasive lobular breast cancer presented with progressive disease on CT scan. Some days after initiation of antineoplastic chemotherapy and anti-HER2 targeted antibody therapy, the patient presented with profuse diarrhoea, neutropaenia, nausea and weakness. Although Clostridium difficile was rapidly tackled as a causative agent of gastrointestinal complaints, clinical situation did not markedly improve despite proper antimicrobial treatment. The patient reported profound lack of energy, while nausea, vomiting and loose stools still persisted. Additionally slightly exaggerated pigmentation of nonsunexposed skin and mucosal areas led us to the assumption of proopiomelanocortin-derived peptide hypersecretion. The combination of highly elevated adrenocorticotropic hormone and low basal cortisol levels taken from a morning blood sample established the diagnosis of adrenal insufficiency due to metastatic burden, leading to a near Addison crisis by gastrointestinal complications of chemo-immune therapy. Administration of hydrocortisone immediately relieved general symptoms .



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Contribution of arterial spin-labelling MRI in a case with immune reconstitution inflammatory syndrome

Central nervous system immune reconstitution inflammatory syndrome (CNS-IRIS), which occurs most often in HIV-infected patients, is an exacerbation of inflammatory reactions related to opportunistic infections as well as primary CNS malignancies both of which mostly occur in HIV-infected patients. However, differential diagnoses are challenging both clinically and radiologically. We describe a patient with CNS-IRIS due to toxoplasmosis whose 11C-methionine uptake suggested lymphoma but whose arterial spin-labelling MRI led to the correct diagnosis.



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Hiding in plain sight: a case of chronic disseminated histoplasmosis with central nervous system involvement

A 64-year-old man presented with gradual onset of confusion, ataxia and 25-pound weight loss over 3 months. MRI of the brain revealed two enhancing cerebellar lesions suspicious for metastases. Positron emission tomography-CT showed enhancement of cervical and axillary lymph nodes. Left axillary lymph node biopsy showed no evidence of malignancy but instead showed fungal organisms morphologically consistent with Histoplasma spp. Disseminated histoplasmosis with central nervous system involvement was suspected. Further history revealed that the patient had been having subjective fever for the past several months. He has had mild pancytopenia for about 2 years, which had not been further evaluated. Additionally, he had an oesophagogastroduodenoscopy 3 months prior to admission, which had shown granulomatous gastritis. Subsequently, the diagnosis of disseminated histoplasmosis was confirmed by serological testing and bone marrow biopsy. The patient was started on liposomal amphotericin B. Unfortunately, the patient had a catastrophic stroke and was transitioned to comfort care measures.



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Persistent sacral chloroma in refractory acute myelogenous leukaemia

Acute myelogenous leukaemia (AML) is a clonal process involving the myeloid subgroup of white blood cells. Chloromas, or myeloid sarcomas, are masses of myeloid leukaemic cells and are a unique aspect of AML. This case involves a 14-year-old boy with AML who presented with multiple chloromas at diagnosis. The patient's extra-calvarial masses and bone marrow involvement responded to chemotherapy; however, his sacral epidural chloromas persisted despite four courses of chemotherapy. The central nervous system, bone marrow and testes have been known to be sanctuary sites for AML. This case illustrates that the sacral spinal canal may potentially be a sanctuary site for the disease process also.



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'Scissor deformity of the toes

Description

A 63-year-old woman presented with an unusual foot deformity involving the left first and second toe causing persistent pain (subjective functional grade 1),1 difficulty in walking and inability to accommodate the foot in regular footwear. She has type 2 diabetes mellitus for the past 8 years and sensorimotor peripheral neuropathy as assessed by vibration perception threshold >25 mV, absence of Semmes-Weinstein monofilament perception and absent ankle reflex. She was a home maker and wore footwear with thumb-hold most of the time. On examination, she had severe hallux valgus (HV) (Manchester Scale: severe score=3)2, anatomical grade 11 and over-riding of second toe over the great toe causing 'scissor deformity' (figure 1). In addition, she had hammer and claw toe deformity involving other digits. She was provided with modified footwear to accommodate great toes with a bunion aid.

Figure 1

Both feet showing...



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Cryptococcal meningitis causing obstructive hydrocephalus in a patient on fingolimod

Cryptococcosis is a recognised opportunistic infection in immunocompromised patients. The long-term adverse effect profile of fingolimod, an immunomodulating agent approved for use in multiple sclerosis in 2010, is only just emerging. We report the first case to our knowledge of a patient presenting with obstructive hydrocephalus secondary to cryptococcal meningitis in the setting of fingolimod therapy. Extensive posterior fossa leptomeningeal inflammation with associated cerebellar oedema resulted in effacement of the fourth ventricle and obstructive hydrocephalus requiring urgent ventriculostomy. Induction, consolidative and maintenance antifungal therapy was prescribed and subsequent conversion to a ventriculoperitoneal shunt was successful in relieving the patient's ventriculomegaly. Awareness of these rare, novel and life-threatening complications of fingolimod-associated immunocompromise is critical as the use of such drugs is expected to rise.



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Publication bias in animal research presented at the 2008 Society of Critical Care Medicine Conference

To determine a direct measure of publication bias by determining subsequent full-paper publication (P) of studies reported in animal research abstracts presented at an international conference (A).

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Grandmothers’ perspectives on the changing context of health in India

The prevalence of obesity and other chronic diseases is increasing in India and around the world. As globalization and social changes are believed to be at the root of these epidemiological changes, these fact...

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Respiratory problems in low-resource settings.

Purpose of review: Chronic breathlessness is common in patients with advanced illness who require palliative care. Achieving good symptom control can be challenging. More people with advanced illness live in low and middle income than in high-income countries, but they are much less likely to receive palliative care. Most of the emerging evidence for the palliative management of chronic breathlessness is from high-income countries. This review explores the context of chronic breathlessness in low-income settings, how evidence for control of chronic breathlessness might relate to these settings and where further work should be focused. Recent findings: Systems for control of noncommunicable diseases (NCDs) in these low-income contexts are poorly developed and health services are often overwhelmed with high levels both of NCD and communicable disease. Multidisciplinary and holistic approaches to disease management are often lacking in these settings. Developing an integrated primary care approach to NCD management is increasingly recognized as a key strategy and this should include palliative care. Most evidence-based approaches to the control of chronic breathlessness could be adapted for use in these contexts Summary: Hand held fans, breathing techniques, graded exercise and use of low-dose morphine can all be used in low-income settings particularly in the context of holistic care. Research is needed into the most effective ways of implementing such interventions and palliative care needs to be promoted as a fundamental aspect of NCD management. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Pediatric Emergency Department Resource Utilization among Children with Primary Care Clinic Contact in the Preceding 2 Days: A Cross-Sectional Study

To characterize pediatric patient contacts with their primary care clinic in the 2 days preceding a visit to the emergency department (ED) and explore how the type of clinic contact relates to ED resource use.

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Health Insurance Coverage among Young Adult Survivors of Pediatric Heart Transplantation

To describe the change in health insurance after heart transplantation among adolescents, and characterize the implications of this change for long-term transplant outcomes.

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Artistic Clues to Psychogenic Tremor Using Pen and Paper

Just as graphologists surmise personality traits based on a person's handwriting, clinicians should use the drawing of Archimedes spirals, lines, and written sentences to differentiate psychogenic from pathologic tremors. Although script patterns vary based on tremor type, Hess et al1 demonstrated that the Archimedes spiral was poorly reproducible in patients with psychogenic tremor. We propose that intact fine motor control in these patients creates script with high amplitude oscillations without compromising legibility.

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A Systematic Review of Comorbidity Measurement Methods for Patients With Nontraumatic Brain Injury in Inpatient Rehabilitation Settings.

This review summarizes comorbidity measurements used on patients with nontraumatic brain injury in inpatient rehabilitation and describes findings on measurement validation and comorbidity profiles. MEDLINE and MEDLINE In-Process, EMBASE, PsycINFO, the Cochrane Database of Systematic Reviews, Health, and Psychosocial Measurement Instruments were searched. Two reviewers screened results according to predefined inclusion and exclusion criteria. Population, statistical methods, comorbidity measurement, justification of its use, and results involving comorbidity were extracted using a standard table. Of 9476 articles retrieved, 16 were included. Comorbidity has been measured using various methods including the following: number and type within various classification systems, such as the International Disease Classification system, the Charlson comorbidity index, Centers for Medicare and Medicaid Services comorbidity tiers and patient comorbidity and complexity level values and subsets of diagnoses within nonadministrative data studies. No studies have assessed the predictive ability of the comorbidity measurements for inpatient rehabilitation outcomes in this population. Because comorbidities are common among the nontraumatic brain injury population, the predictive validity of comorbidity measurements should be assessed to determine the most appropriate measure to predict or risk adjust rehabilitation outcomes, which has implications for the development of clinical guidelines, and to inform health service research, planning, and delivery. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Functional Balance Deterioration on Daily Activities in Patients With Migraine: A Controlled Study.

Objective: This study aimed to assess functional activities in different subgroups of patients with migraine. Design: One-hundred forty subjects were uniformly divided into the following four groups: headache-free controls, migraine with aura, without aura, and chronic migraine. Subjects performed the tests walk across, tandem walk, sit to stand, and step up and over at the Balance Master system (Neurocom). Results: All migraine groups had slower velocity and shorter step length at the walk across test (P

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Wnt/ss-catenin activation by epigenetically aberrant stroma drives myelodysplastic syndrome

The bone marrow microenvironment influences malignant hematopoiesis but how it promotes leukemogenesis has not been elucidated. Additionally, the role of the bone marrow stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. In this study, we conducted a DNA methylome analysis of bone marrow-derived stromal cells from myelodysplastic syndrome (MDS) patients and observed widespread aberrant cytosine hypermethylation occurring preferentially outside CpG islands. Stroma derived from 5-azacytidine-treated patients lacked aberrant methylation and DNMTi treatment of primary MDS stroma enhanced its ability to support erythroid differentiation. An integrative expression analysis revealed that the WNT pathway antagonist FRZB was aberrantly hypermethylated and underexpressed in MDS stroma. This result was confirmed in an independent set of sorted, primary MDS-derived mesenchymal cells. We documented a WNT/ß-catenin activation signature in CD34+ cells from advanced cases of MDS where it associated with adverse prognosis. Constitutive activation of ß-catenin in hematopoietic cells yielded lethal myeloid disease in a NUP98-HOXD13 mouse model of MDS, confirming its role in disease progression. Our results define novel epigenetic changes in the bone marrow microenvironment which lead to ß-catenin activation and disease progression of MDS.

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Targeting histone demethylases in MYC-driven neuroblastomas with ciclopirox

Histone lysine demethylases facilitate the activity of oncogenic transcription factors including possibly MYC. Here we show that multiple histone demethylases influence the viability and poor prognosis of neuroblastoma cells where MYC is often overexpressed. We also identified the approved small molecule antifungal agent ciclopirox as a novel pan-histone demethylase inhibitor. Ciclopirox targeted several histone demethylases including KDM4B implicated in MYC function. Accordingly, ciclopirox inhibited Myc signaling in parallel with mitochondrial oxidative phosphorylation, resulting in suppression of neuroblastoma cell viability and inhibition of tumor growth associated with an induction of differentiation. Our findings provide new insights into epigenetic regulation of MYC function and suggest a novel pharmacologic basis to target histone demethylases as an indirect MYC targeting approach for cancer therapy.

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A Technique of Awake Bronchoscopic Endotracheal Intubation for Respiratory Failure in Patients With Right Heart Failure and Pulmonary Hypertension.

Objective: Patients with pulmonary hypertension and right heart failure have a high risk of clinical deterioration and death during or soon after endotracheal intubation. The effects of sedation, hypoxia, hypoventilation, and changes in intrathoracic pressure can lead to severe hemodynamic instability. In search for safer approach to endotracheal intubation in this cohort of patients, we evaluate the safety and feasibility of an alternative intubation technique. Data Sources: Retrospective data analysis. Study Selection: Two medical ICUs in large university hospitals in the United States. Data Extraction: We report a case series of nine nonconsecutive patients with compromised right heart function, pulmonary hypertension, and severe acute hypoxemic respiratory failure who underwent endotracheal intubation with a novel technique combining awake bronchoscopic intubation supported with nasally delivered noninvasive positive pressure ventilation or high-flow nasal cannula. Data Synthesis: All patients were intubated in the first attempt without major complications and eight patients (88%) were alive 24 hours after intubation. Systemic hypotension was the most frequent complication following the procedure. Conclusions: Awake bronchoscopic intubation supported with a noninvasive positive pressure delivery systems may be feasible alternative to standard direct laryngoscopy approach. Further studies are needed to better assess its safety and applicability. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Closed-Loop- and Decision-Assist-Guided Fluid Therapy of Human Hemorrhage.

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Objectives: We sought to evaluate the efficacy, efficiency, and physiologic consequences of automated, endpoint-directed resuscitation systems and compare them to formula-based bolus resuscitation. Design: Experimental human hemorrhage and resuscitation. Setting: Clinical Research Laboratory. Subjects: Healthy volunteers. Interventions: Subjects (n = 7) were subjected to hemorrhage and underwent a randomized fluid resuscitation scheme on separate visits 1) formula-based bolus resuscitation; 2) semiautonomous (decision assist) fluid administration; and 3) fully autonomous (closed loop) resuscitation. Hemodynamic variables, volume shifts, fluid balance, and cardiac function were monitored during hemorrhage and resuscitation. Treatment modalities were compared based on resuscitation efficacy and efficiency. Measurements and Main Results: All approaches achieved target blood pressure by 60 minutes. Following hemorrhage, the total amount of infused fluid (bolus resuscitation: 30 mL/kg, decision assist: 5.6 +/- 3 mL/kg, closed loop: 4.2 +/- 2 mL/kg; p

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Characteristics and Outcome of Cancer Patients Admitted to the ICU in England, Wales, and Northern Ireland and National Trends Between 1997 and 2013.

Objective: To describe trends in outcomes of cancer patients with an unplanned admission to the ICU between 1997 and 2013 and to identify risk factors for mortality of those admitted between 2009 and 2013. Design: Retrospective analysis. Setting: Intensive Care National Audit & Research Centre Case Mix Programme Database including data of ICUs in England, Wales, and Northern Ireland. Patients: Patients (99,590) with a solid tumor and 13,538 patients with a hematological malignancy with an unplanned ICU admission between 1997 and 2013; 39,734 solid tumor patients and 6,652 patients with a hematological malignancy who were admitted between 2009 and 2013 were analyzed in depth. Interventions: None. Measurements and Main Results: In solid tumor patients admitted between 2009 and 2013, hospital mortality was 26.4%. Independent risk factors for hospital mortality were metastatic disease (odds ratio, 1.99), cardiopulmonary resuscitation before ICU admission (odds ratio, 1.63), Intensive Care National Audit & Research Centre Physiology score (odds ratio, 1.14), admission for gastrointestinal (odds ratio, 1.12), respiratory (odds ratio, 1.48) or neurological (odds ratio, 1.65) reasons, and previous ICU admission (odds ratio, 1.18). In patients with a hematological malignancy admitted between 2009 and 2013, hospital mortality was 53.6%. Independent risk factors for hospital mortality were age (odds ratio, 1.02), cardiopulmonary resuscitation before ICU admission (odds ratio, 1.90), Intensive Care National Audit & Research Centre Physiology Score (odds ratio, 1.12), admission for hematological (odds ratio, 1.48) or respiratory (odds ratio, 1.56) reasons, bone marrow transplant (odds ratio, 1.53), previous ICU admission (odds ratio, 1.43), and mechanical ventilation within 24 hours of admission (odds ratio, 1.33). Trend analysis showed a significant decrease in ICU and hospital mortality and length of stay between 1997 and 2013 despite little change in severity of illness during this time. Conclusions: Between 1997 and 2013, the outcome of cancer patients with an unplanned admission to ICU improved significantly. Among those admitted between 2009 and 2013, independent risk factors for hospital mortality were age, severity of illness, previous cardiopulmonary resuscitation, previous ICU admission, metastatic disease, and admission for respiratory reasons. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Technologic Distractions (Part 1): Summary of Approaches to Manage Alert Quantity With Intent to Reduce Alert Fatigue and Suggestions for Alert Fatigue Metrics.

Objective: To provide ICU clinicians with evidence-based guidance on tested interventions that reduce or prevent alert fatigue within clinical decision support systems. Design: Systematic review of PubMed, Embase, SCOPUS, and CINAHL for relevant literature from 1966 to February 2017. Patients: Focus on critically ill patients and included evaluations in other patient care settings, as well. Interventions: Identified interventions designed to reduce or prevent alert fatigue within clinical decision support systems. Measurements and Main Results: Study selection was based on one primary key question to identify effective interventions that attempted to reduce alert fatigue and three secondary key questions that covered the negative effects of alert fatigue, potential unintended consequences of efforts to reduce alert fatigue, and ideal alert quantity. Data were abstracted by two reviewers independently using a standardized abstraction tool. Surveys, meeting abstracts, "gray" literature, studies not available in English, and studies with non-original data were excluded. For the primary key question, articles were excluded if they did not provide a comparator as key question 1 was designed as a problem, intervention, comparison, and outcome question. We anticipated that reduction in alert fatigue, including the concept of desensitization may not be directly measured and thus considered interventions that reduced alert quantity as a surrogate marker for alert fatigue. Twenty-six articles met the inclusion criteria. Conclusion: Approaches for managing alert fatigue in the ICU are provided as a result of reviewing tested interventions that reduced alert quantity with the anticipated effect of reducing fatigue. Suggested alert management strategies include prioritizing alerts, developing sophisticated alerts, customizing commercially -available alerts, and including end user opinion in alert selection. Alert fatigue itself is studied less frequently, as an outcome, and there is a need for more precise evaluation. Standardized metrics for alert fatigue is needed to advance the field. Suggestions for standardized metrics are provided in this document. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Biodegradation and biodetoxification of Fusarium mycotoxins by Sphaerodes mycoparasitica

A fungus Sphaerodes mycoparasitica SMCD 2220-01 is a host specific mycoparasite against plant pathogenic Fusarium species. Fusarium spp. are producing a plethora of mycotoxins including zearalenone (ZEN), deoxyni...

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Effect of Eudragit S100 nanoparticles and alginate chitosan encapsulation on the viability of Lactobacillus acidophilus and Lactobacillus rhamnosus

In this study, we examined a novel method of microencapsulation with calcium alginate-chitosan and Eudragit S100 nanoparticles for the improving viability of probiotic bacteria, Lactobacillus acidophilus and Lact...

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Photosynthetic poly-β-hydroxybutyrate accumulation in unicellular cyanobacterium Synechocystis sp. PCC 6714

Poly-β-hydroxybutyrate (PHB) production from CO2 has the potential to reduce the production cost of this biodegradable polyesters, and also to make the material more sustainable compared to utilization of sugar f...

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An Investigation of Protective Effects of Litium Borate on Blood and Histopathological Parameters in Acute Cadmium-Induced Rats

Abstract

This study was carried out to determine the protective effects of lithium borate (LTB) on blood parameters and histopathological findings in experimentally induced acute cadmium (Cd) toxicity in rats. Twenty-eight male Wistar albino rats were used, weighing 200–220 g, and they were randomly divided into four groups, including one control and the following three experimental groups: a Cd group (0.025 mmol/kg), a LTB group (15 mg/kg/day orally for 5 days), and a LTB + Cd group (15 mg/kg/day orally for 5 days and Cd 0.025 mmol/kg by intraperitoneal injection on the fifth day). All the rats in the study were anesthetized with ketamine at the end of the sixth day, blood was taken from their hearts, and then the rats were decapitated. The values in the control and LTB group were usually close to each other. White blood cell (WBC), neutrophil %, and C-reactive protein (CRP) levels increased in the Cd and LTB + Cd groups while lymphocyte and monocyte levels decreased in a statistically significant manner, in comparison to the other groups. It was determined that the levels of red blood cells (RBCs), hematocrit (Htc), and hemoglobin (Hb) did not change in the groups. The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the Cd and LTB + Cd groups significantly increased, in comparison to the other groups, while the glucose, alkaline phosphatase (ALP), albumin (ALB), and total protein (TP) levels decreased. According to histopathological findings in the control and LTB groups, the liver and kidney tissues were found to have normal histological structures. In the Cd group, severe necrotic hemorrhagic hepatitis, mild steatosis, and mononuclear cell infiltration were detected in the liver. In the LTB + Cd group, degeneration and mild mononuclear cell infiltration were found in the liver. Regarding the kidney tissue in the Cd group, severe intertubular hyperemia in both kidney cortex and medulla, as well as degeneration and necrosis in the tubulus epithelium, was observed. In the LTB + Cd group, mild interstitial hyperemia and mononuclear cell infiltration was detected. Resultantly, it can be said that LTB at this dose has non-toxic effects and some beneficial effects for liver and kidney damage caused by acute Cd toxicity.



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The impact of methicillin-resistant S. aureus on length of stay, readmissions and costs: a register based case-control study of patients hospitalized in Norway

Patients with methicillin-resistant S. aureus (MRSA) are thought to incur additional costs for hospitals due to longer stay and contact isolation. The aim of this study was to assess the costs associated with MRS...

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Immunodeficiency in Pancreatic Adenocarcinoma with Diabetes Revealed by Comparative Genomics

Purpose: Pancreatic adenocarcinomas (PAAD) often are not diagnosed until their late stages leaving no effective treatments. Currently immunotherapy provides a promising treatment option against this malignancy. However, a set of immunotherapy agents benefit patients with many types of cancer, but not PAAD. Sharing the origin in the same organ, diabetes and PAAD tend to occur concurrently. We aimed to identify the impact of diabetes on immunotherapy of PAAD by conducting a comparative genomics analysis.    <p>Experimental Design: We analyzed levels 3 PAAD genomics data (RNAseq, miRNAseq, DNA methylation, somatic copy number and somatic mutation) from TCGA and Firehose. The differential molecular profiles in PAAD with/out diabetes were performed by the differential gene expression, pathway analysis, epigenetic regulation, somatic copy number alteration and somatic gene mutation.</p> <p>Results: Differential gene expression analysis revealed a strong enrichment of immunogenic signature genes in diabetic individuals including PD-1 and CTLA4 that were currently targetable for immunotherapy. Pathway analysis further implied that diabetic individuals were defective in immune modulation genes. Somatic copy number aberration (SCNA) analysis showed a higher frequency of amplification and deletion occurred in the cohort without diabetes. Integrative analysis revealed strong association between differential gene expression and epigenetic regulations, however seemed not affected by SCNAs. Importantly, our somatic mutation analysis showed that the occurrence of diabetes in PAAD was associated with a large set of gene mutations encoding genes participating in immune modulation.</p> Conclusions: Our analysis reveals the impact of diabetes on immunodeficiency in PAAD patients and provides novel insights into new therapeutic opportunities.



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Anti-diabetic activity of aerial parts of Sarcopoterium spinosum

Sarcopoterium spinosum (S. spinosum) is used by Bedouin medicinal practitioners for the treatment of diabetes. While the anti-diabetic activity of S. spinosum root extract was validate...

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Chinese acute ischemic stroke treatment outcome registry (CASTOR): protocol for a prospective registry study on patterns of real-world treatment of acute ischemic stroke in China

Stroke presents a serious health problem in China. Despite progresses made in recent years, there is still a lack of effective treatments for acute ischemic stroke (AIS) in clinical practices.

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Atar Extension Cables by Oscor: Recall - Cable Separating from Connector

[Posted 07/06/2017] AUDIENCE: Cardiology ISSUE: During the use of some Atar extension cables, the cable was separating from the connector at the proximal end. The analysis of the returned devices revealed a change in the manufacturing sequence...

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Guidelines for low intensity transcranial electrical stimulation – an overdue step in a fairly uncontrolled field.

Non-invasive brain stimulation is an important, rapidly growing field in modern clinical neurophysiology. While high voltage transcranial electrical stimulation and transcranial magnetic stimulation and its variants have been long around, low intensity electrical transcranial stimulation (LIETS) is relatively young and is one of the fastest expanding and most promising areas of clinical neurophysiology. LIETS in this context means stimulus intensities of < 4mA for up to 60 min as described by Bikson et al.

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Early childhood myoclonic epilepsy: An independent genetic generalized epilepsy with myoclonic seizures as the main seizure type

Genetic (idiopathic) generalized epilepsies (GGEs) constitute one-third of all epilepsies (ILAE, 1989; Engel and ILAE, 2001). They are genetically determined and affect otherwise normal individuals of both sexes. GGEs manifest with absences, myoclonic jerks or generalized tonic-clonic seizures (GTCS), alone or in varying combinations and severity (Panayiotopoulos, 2005). According to the age at onset, GGEs proposed by International League Against Epilepsy (ILAE) include: myoclonic epilepsy in infancy (MEI), epilepsy with myoclonic absences (MAE), epilepsy with myoclonic atonic seizures also named as Doose syndrome, childhood absence epilepsy (CAE), juvenile absence epilepsies (JAE), and juvenile myoclonic epilepsy (JME) and so on (Berg et al., 2010).

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Measuring alterations in oscillatory brain networks in Schizophrenia with resting-state MEG: State-of-the-art and methodological challenges

Schizophrenia (SZ) is a severe psychotic disorder with important cognitive impairments. It is one of the most debilitating psychiatric illnesses. Worldwide, an estimated 21 million individuals suffer from schizophrenia and other psychotic illnesses (World Health Organization 2016). SZ patients display psychotic symptoms (e.g., hallucination, delusion, etc.) and often mood symptoms such as depression (American Psychiatric Association, 2013). Despite a thriving body of research, progress in understanding the pathophysiological mechanisms that underlie the symptoms of the disorder, and its heterogeneous nature, is relatively slow.

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The impact of accelerated high frequency rTMS on brain neurochemicals in treatment-resistant depression: Insights from 1H MR spectroscopy

Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based non-invasive clinical tool to treat patients suffering from major depression (Lefaucheur et al. 2014). Compared to electroconvulsive therapy (ECT) the application of rTMS seems rather benign: subjects are fully awake, no anesthesia or additional medication is needed. Only minor side effects - if any - are to be expected (George et al. 2013). Nevertheless, to induce enough current to excite cortical neurons at a depth of 2–2.5 cm beneath the scalp, the changing current which passes through the coil develops an electromagnetic field of about 1.5–3 Tesla (Hallett 2000; George and Belmaker 2007).

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Atar Extension Cables by Oscor: Recall - Cable Separating from Connector

[Posted 07/06/2017] AUDIENCE: Cardiology ISSUE: During the use of some Atar extension cables, the cable was separating from the connector at the proximal end. The analysis of the returned devices revealed a change in the manufacturing sequence...

http://ift.tt/2sLRXOA

Periodontal regenerative therapy with enamel matrix derivative in the treatment of intrabony defects: a prospective 2-year study

To date, enamel matrix derivative (EMD) has been considered to be one of the few biomaterials for clinical use capable of demonstrating true periodontal regeneration. The aim of this two-center prospective cli...

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Identification and characterization of Burkholderia multivorans CCA53

A lignin-degrading bacterium, Burkholderia sp. CCA53, was previously isolated from leaf soil. The purpose of this study was to determine phenotypic and biochemical features of Burkholderia sp. CCA53.

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Extrapolative microRNA precursor based SSR mining from tea EST database in respect to agronomic traits

Tea (Camellia sinensis, (L.) Kuntze) is considered as most popular drink across the world and it is widely consumed beverage for its several health-benefit characteristics. These positive traits primarily rely on...

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Quality of multiple sclerosis out-patient health care services with focus on patient reported experiences

To investigate multiple sclerosis (MS) patients' satisfaction with out-patient follow-up in a general neurological hospital department. Patients with definite MS living in Vest-Agder county, Norway were invite...

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RBM38 is involved in TGF-β-induced epithelial-to-mesenchymal transition by stabilising zonula occludens-1 mRNA in breast cancer



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Lurbinectedin reduces tumour-associated macrophages and the inflammatory tumour microenvironment in preclinical models



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Non-invasive prediction of recurrence in bladder cancer by detecting somatic TERT promoter mutations in urine



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Integrating cytokines and angiogenic factors and tumour bulk with selected clinical criteria improves determination of prognosis in advanced renal cell carcinoma



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Comprehensive analysis of copy number aberrations in microsatellite stable colon cancer in view of stromal component



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Commonly used medications and endometrial cancer survival: a population-based cohort study



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Correlation between circulating mutant DNA and metabolic tumour burden in advanced non-small cell lung cancer patients



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Clinicopathological Significance of Micropapillary Pattern in Lung Adenocarcinoma

Abstract

The aim of this study was to elucidate the clinicopathological characteristics of the micropapillary (MP) subtype and its correlation with survival in lung adenocarcinoma. We investigated the clinicopathological characteristics, including the incidence, sex, smoking history, tumor size, lymph node metastasis, lymphovascular invasion, distant metastasis, genetic alteration, and prognosis in lung adenocarcinoma with the MP pattern through a meta-analysis. From 48 eligible studies, 19,502 lung adenocarcinomas were included. The incidence rate of the MP pattern was 0.101 [95% confidence interval (CI) 0.075–0.136]. There was no significant difference between stage I and III tumors. Lung adenocarcinoma with the MP pattern showed higher rates of lymphatic invasion (0.526, 95% CI 0.403–0.645). MP pattern was found in 0.150 (95% CI 0.008–0.790) of lung adenocarcinoma with distant metastasis. In lung adenocarcinoma with the MP pattern, the estimated rates of ALK, EGFR, and KRAS mutations were 0.102 (95% CI 0.027–0.322), 0.620 (95% CI 0.444–0.769), and 0.118 (95% CI 0.027–0.393), respectively. The MP pattern of lung adenocarcinoma was significantly correlated with worse overall and disease-free survival rates (hazard ratio 1.704, 95% CI 1.216–2.387, and 2.082, 95% CI 1.541–2.813, respectively). Taken together, identification of the MP pattern in lung adenocarcinoma is useful for prediction of clinicopathological characteristics and prognosis of patients.



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First report of cavitary pneumonia due to community-acquired Acinetobacter pittii, study of virulence and overview of pathogenesis and treatment

Acinetobacter pittii is a nosocomial pathogen rarely involved in community-acquired infections. We report for the first time that A. pittii can be responsible for cavitary community-ac...

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Role of outpatient parenteral antibiotic therapy in the treatment of community acquired skin and soft tissue infections in Singapore

Treatment of community acquired skin and soft tissue infections (SSTIs) is a common indication for outpatient parenteral antibiotic therapy (OPAT) in USA, UK and Australasia, however data from Asia are lacking...

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Pseudonocardia carboxydivorans in human cerebrospinal fluid: a case report in a patient with traumatic brain injury

Members of the genus Pseudonocardia have been widely reported and recovered from several ecosystems, such as soil samples and plant samples. Pseudonocardia bacteria colonize the microbial communities on the integ...

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Epidemiology of pharyngitis as reported by Zambian school children and their families: implications for demand-side interventions to prevent rheumatic heart disease

Prompt and appropriate treatment of streptococcal pharyngitis decreases the risk of acute rheumatic fever and rheumatic heart disease (RHD). Understanding public perceptions and behaviors related to sore throa...

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Decreasing seroprevalence of herpes simplex virus type 1 and type 2 in Germany leaves many people susceptible to genital infection: time to raise awareness and enhance control

Herpes simplex infections (HSV1/2) are characterized by recurrent symptoms, a risk of neonatal herpes, and the facilitation of HIV transmission. In Germany, HSV1/2 infections are not notifiable and data are sc...

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Microglia contribute to normal myelinogenesis and to oligodendrocyte progenitor maintenance during adulthood

Abstract

Whereas microglia involvement in virtually all brain diseases is well accepted their role in the control of homeostasis in the central nervous system (CNS) is mainly thought to be the maintenance of neuronal function through the formation, refinement, and monitoring of synapses in both the developing and adult brain. Although the prenatal origin as well as the neuron-centered function of cortical microglia has recently been elucidated, much less is known about a distinct amoeboid microglia population formerly described as the "fountain of microglia" that appears only postnatally in myelinated regions such as corpus callosum and cerebellum. Using large-scale transcriptional profiling, fate mapping, and genetic targeting approaches, we identified a unique molecular signature of this microglia subset that arose from a CNS endogenous microglia pool independent from circulating myeloid cells. Microglia depletion experiments revealed an essential role of postnatal microglia for the proper development and homeostasis of oligodendrocytes and their progenitors. Our data provide new cellular and molecular insights into the myelin-supporting function of microglia in the normal CNS.



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Affected female carriers of MTM1 mutations display a wide spectrum of clinical and pathological involvement: delineating diagnostic clues

Abstract

X-linked myotubular myopathy (XLMTM), a severe congenital myopathy, is caused by mutations in the MTM1 gene located on the X chromosome. A majority of affected males die in the early postnatal period, whereas female carriers are believed to be usually asymptomatic. Nevertheless, several affected females have been reported. To assess the phenotypic and pathological spectra of carrier females and to delineate diagnostic clues, we characterized 17 new unrelated affected females and performed a detailed comparison with previously reported cases at the clinical, muscle imaging, histological, ultrastructural and molecular levels. Taken together, the analysis of this large cohort of 43 cases highlights a wide spectrum of clinical severity ranging from severe neonatal and generalized weakness, similar to XLMTM male, to milder adult forms. Several females show a decline in respiratory function. Asymmetric weakness is a noteworthy frequent specific feature potentially correlated to an increased prevalence of highly skewed X inactivation. Asymmetry of growth was also noted. Other diagnostic clues include facial weakness, ptosis and ophthalmoplegia, skeletal and joint abnormalities, and histopathological signs that are hallmarks of centronuclear myopathy such as centralized nuclei and necklace fibers. The histopathological findings also demonstrate a general disorganization of muscle structure in addition to these specific hallmarks. Thus, MTM1 mutations in carrier females define a specific myopathy, which may be independent of the presence of an XLMTM male in the family. As several of the reported affected females carry large heterozygous MTM1 deletions not detectable by Sanger sequencing, and as milder phenotypes present as adult-onset limb-girdle myopathy, the prevalence of this myopathy is likely to be greatly underestimated. This report should aid diagnosis and thus the clinical management and genetic counseling of MTM1 carrier females. Furthermore, the clinical and pathological history of this cohort may be useful for therapeutic projects in males with XLMTM, as it illustrates the spectrum of possible evolution of the disease in patients surviving long term.



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Novopen Echo Insulin Delivery Device by Novo Nordisk: Recall - May Crack or Break If Exposed To Certain Chemicals

Audience: Patient, Pharmacy [Posted 07/06/2017] ISSUE: Novo Nordisk is initiating a recall of insulin cartridge holders used in a small number of NovoPen Echo batches because they may crack or break if exposed to certain chemicals, like certain...

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Ultra-Sten and D-Zine Capsules by Hardcore Formulations: Recall - Contains Anabolic Steroids

Audience: Consumer [Posted 07/06/2017] ISSUE: Hardcore Formulations is voluntarily recalling all lots and expiration dates of Ultra-Sten and D-Zine capsules to the consumer level. These products are labeled to contain methylstenbolone (Ultra-Sten)...

http://ift.tt/2tuT8Pr

Novopen Echo Insulin Delivery Device by Novo Nordisk: Recall - May Crack or Break If Exposed To Certain Chemicals

Audience: Patient, Pharmacy [Posted 07/06/2017] ISSUE: Novo Nordisk is initiating a recall of insulin cartridge holders used in a small number of NovoPen Echo batches because they may crack or break if exposed to certain chemicals, like certain...

http://ift.tt/2sKVgFz

Ultra-Sten and D-Zine Capsules by Hardcore Formulations: Recall - Contains Anabolic Steroids

Audience: Consumer [Posted 07/06/2017] ISSUE: Hardcore Formulations is voluntarily recalling all lots and expiration dates of Ultra-Sten and D-Zine capsules to the consumer level. These products are labeled to contain methylstenbolone (Ultra-Sten)...

http://ift.tt/2tuT8Pr

Classification of caesarean section and normal vaginal deliveries using foetal heart rate signals and advanced machine learning algorithms

Visual inspection of cardiotocography traces by obstetricians and midwives is the gold standard for monitoring the wellbeing of the foetus during antenatal care. However, inter- and intra-observer variability ...

http://ift.tt/2uvDGCL

A Filtration-based Method of Preparing High-quality Nuclei from Cross-linked Skeletal Muscle for Chromatin Immunoprecipitation

56013fig1.jpg

We present a filtration-based protocol to isolate high-quality nuclei from cross-linked mouse skeletal muscle wherein we removed the need for ultracentrifugation, making it easily applicable. We show that chromatin prepared from the nuclei is suitable for chromatin immunoprecipitation and likely chromatin immunoprecipitation sequencing studies.

http://ift.tt/2tv17w5

Platinum pyrithione induces apoptosis in chronic myeloid leukemia cells resistant to imatinib via DUB inhibition-dependent caspase activation and Bcr-Abl downregulation

Platinum pyrithione induces apoptosis in chronic myeloid leukemia cells resistant to imatinib via DUB inhibition-dependent caspase activation and Bcr-Abl downregulation

Cell Death and Disease 8, e2913 (July 2017). doi:10.1038/cddis.2017.284

Authors: Xiaoying Lan, Chong Zhao, Xin Chen, Peiquan Zhang, Dan Zang, Jinjie Wu, Jinghong Chen, Huidan Long, Li Yang, Hongbiao Huang, Xuejun Wang, Xianping Shi & Jinbao Liu



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Conservation and divergence of mitochondrial apoptosis pathway in the Pacific oyster, Crassostrea gigas

Conservation and divergence of mitochondrial apoptosis pathway in the Pacific oyster, Crassostrea gigas

Cell Death and Disease 8, e2915 (July 2017). doi:10.1038/cddis.2017.307

Authors: Yingxiang Li, Linlin Zhang, Tao Qu, Xueying Tang, Li Li & Guofan Zhang



http://ift.tt/2tlInRk

The BH3-only proteins BIM and PUMA are not critical for the reticulocyte apoptosis caused by loss of the pro-survival protein BCL-XL

The BH3-only proteins BIM and PUMA are not critical for the reticulocyte apoptosis caused by loss of the pro-survival protein BCL-XL

Cell Death and Disease 8, e2914 (July 2017). doi:10.1038/cddis.2017.304

Authors: Alex RD Delbridge, Brandon J Aubrey, Craig Hyland, Jonathan P Bernardini, Ladina Di Rago, Jean-Marc Garnier, Guillaume Lessene, Andreas Strasser, Warren S Alexander & Stephanie Grabow



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Sphingosine kinase 2 activates autophagy and protects neurons against ischemic injury through interaction with Bcl-2 via its putative BH3 domain

Sphingosine kinase 2 activates autophagy and protects neurons against ischemic injury through interaction with Bcl-2 via its putative BH3 domain

Cell Death and Disease 8, e2912 (July 2017). doi:10.1038/cddis.2017.289

Authors: Dan-Dan Song, Tong-Tong Zhang, Jia-Li Chen, Yun-Fei Xia, Zheng-Hong Qin, Christian Waeber & Rui Sheng



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Effects of different substrates/growth media on microbial community of saliva-derived biofilm

Abstract
The aims of this study were to investigate the effects of substrates (glass versus hydroxyapatite [HA]) and growth media (SHI medium versus a modified artificial saliva medium with cysteine) on the microbial community of saliva-derived biofilm in vitro. 16S rRNA gene sequencing technology was used to analyze the microbial community of saliva-derived biofilm cultured for 72 h anaerobically. The metagenomes of biofilms were predicted from the clusters of orthologous groups. No significant difference was found between the saliva-derived biofilms grown on HA and glass in ACE, Chao, Shannon and Simpson indices. The abundances of only a few bacteria on HA were significantly different from those on glass with a low relative abundance (<0.5%). Compared with the biofilms developed in a modified artificial saliva medium with cysteine, biofilms in SHI medium were significantly higher (P < 0.05) in diversity. Linear discriminant analysis coupled with effect size measurement showed that some obligate anaerobic genera (Lactobacillus, Veillonella, Porphyromonas and Leptotrichia) were more abundant in SHI medium biofilms. The biofilms grown in different media were also significantly different in predicted gene categories. In conclusion, the growth media, not the substrates, have significant effects on the microbial community of saliva-derived biofilm in vitro.

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Erratum



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Relationship between β-lactamase production and resistance phenotype in Klebsiella pneumoniae strains

Abstract
This study was designed to evaluate the resistance phenotypes of β-lactamases-producing Klebsiella pneumoniae strains. The antibiotic susceptibility and β-lactamase activity of K. pneumoniae strains, including antibiotic-sensitive K. pneumoniae (KPWT), ciprofloxacin-induced resistant K. pneumoniae (KPCIP) and clinically isolated K. pneumoniae strains (KPCI237, KPCI263 and KPCI272) were determined in the absence and presence of β-lactamase inhibitors (BLI 489, sulbactam, clavulanate and tazobactam). All strains were highly resistant to ampicillin in the absence of β-lactamase inhibitors (MIC≥ 512 μg mL−1). In the presence of clavulanate, the MICs of ampicillin and piperacillin against KPWT were decreased by > 64-fold and 4-fold, respectively. The resistance of KPCI263 to cefotaxime, ceftazidime, ceftriaxone and piperacillin were increased in the presence of BLI-489. The antibiotic susceptibility of KPCI237 to β-lactams was not noticeably changed in the presence of β-lactamase inhibitor (clavulanate, sulbactam or tazobactam). KPWT, KPCIP and KPCI272 were positive for blaSHV, blaAmpC and blaFOX/MOX; KPCI237 for blaSHV and blaAmpC; and KPCI263 for blaSHV and blaOXA-48. The antibiotic susceptibility corresponded well with the results obtained from dual disc diffusion assay, which was in good agreement with the β-lactamase production. The results provide useful information for understanding the resistance phenotypes in association with β-lactamase production.

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Stress-responsively modulated ymdAB-clsC operon plays a role in biofilm formation and apramycin susceptibility in Escherichia coli

Abstract
The YmdB protein, an inhibitor of biofilm formation and an inducer of apramycin susceptibility in Escherichia coli (E. coli), is part of a putative operon. However, transcription of this operon and its subsequent effects on biological pathways has not been fully studied. Here, we characterized the operon in terms of promoter activity, transcription and function. Promoter activity assays identified two new growth- and cold-shock-responsive upstream (PymdA) and inner (PclsC) promoters, respectively. Moreover, investigation of the operon-derived transcripts identified different polycistronic transcripts harboring multiple heterogeneous 3΄ ends. Overexpression of YmdA or ClsC proteins inhibited biofilm formation and affected apramycin susceptibility, a process dependent on the sucA gene, suggesting that the operon genes or their encoded proteins are functionally linked. Additional investigation of the effects of polycistronic transcripts on the response of E. coli cells to apramycin revealed that transcripts containing ymdA (–213 to +27) are required for apramycin susceptibility. Thus, ymdAB-clsC is a new stress-responsive operon that plays a role in inhibiting undesired biofilm forming and antibiotic-resistant bacterial populations.

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In Vivo Evaluation of the Mechanical and Viscoelastic Properties of the Rat Tongue

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We describe a surgical procedure in an anesthetized rat model for determining the muscle tone and viscoelastic properties of the tongue. The procedure involves specific stimulation of the hypoglossal nerves and application of passive Lissajous force/deformation curves to the muscle.

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Cancer Researchers Report Progress in Studying Exceptional Responders

Researchers who study exceptional responders—patients who have dramatic and long-lasting responses to treatments for cancer that were not effective for most similar patients—met recently to discuss the state of the science in this emerging field.



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Evaluation of silybum marinaum efficacy on University of Wisconsin and histidine-tryptophan-ketoglutarate solutions latter the damage of the perfused liver

Abstract Purpose: To investigate the hepatoprotective and antioxidant effeicacies of Silybum marianum's (silymarin, S) on University of Wisconsin (UW) and histidinetryptophan-ketoglutarate (HTK) preservation solutions. Methods: Thirty two Wistar albino adult male rats were used. Group 1: UW group, Group 2: UW + Silymarin group(S), Group 3: HTK group, Group 4: HTK + silymarin group (S), respectively. Silymarin was enforced intraperitoneally before the surgery. Biopsies were enforced in 0, 6 and 12.hours to investigate. Results: Biochemical parameters examined in alanine aminotransferase (ALT), furthermore superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in rats were also evaluated. Detected histopathological changings were substantially declining in the groups that received silymarin, cellular damage was decreased significantly in HTK + Silymarin group, according to other groups. It has been identified as the most effective group was HTK + silymarin group in evaluation of ALT, electron microscopic results, also decreased MDA and elevated in SOD, and CAT activity. Caspase 3 analysis showed a substantial lower apoptosis ratio in the silymarin groups than in the non-performed groups (p<0.05). Conclusion: Histidinetryptophan-ketoglutarate+silymarin group provides better hepatoprotection than other groups, by decreasing the hepatic pathologic damage, delayed changes that arise under cold ischemic terms.

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The effects of chitosan oligosaccharides on OPG and RANKL expression in a rat osteoarthritis model

Abstract Purpose: To investigate the effect of chitosan oligosaccharides (COS) against osteoarthritis (OA) and preliminarily discuss the osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL) and RANK expression in a rat OA model. Methods: Thirty-six 6-week-old Male SD rats were randomly divided into three groups: sham-operated group(CON), OA-induction group(OA), COS intervention group(n=12/group). At 4 weeks after the operation, COS (50 ul) intervention weekily for consecutive 5 weeks. The OA and CON groups received an injection of 50 ul physiological saline. At death, 11 weeks following surgery, cartilage was harvested and total RNA and protein were extracted. Both the morphological changes of the cartilage were observed and harvested the total RNA and protein. Meanwhile, the expression of OPG, RANKL and RANK in cartilage were determined. Results: The expression of OPG and RANKL were both enhanced in the cartilage of the OA model. Compared with the OA group, COS treatment improved the cartilage damage (both extent and grade). Furthermore, the COS group showed highly OPG and lower RANKL. Simultaneously, COS treatment upregulated the ratio of OPG/RANKL and downregulated the RANKL/RANK. Conclusion: Chitosan oligosaccharides may be used as a unique biological agent to prevent and treat osteoarthritis, and this effect is associated with modulation of the expression of osteoprotegerin and receptor activator of NF-κB ligand.

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Dexmedetomidine protects against renal ischemia and reperfusion injury by inhibiting the P38-MAPK/TXNIP signaling activation in streptozotocin induced diabetic rats

Abstract Purpose: To determine whether dexmedetomidine (DEX) could attenuate acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) in streptozotocin (STZ)-induced diabetic rats. Methods: Four groups each containing six rats were created (sham control(S), diabetes-sham (DS), diabetes I/R (DI/R), and diabetes-I/R-dexmedetomidine (DI/R-DEX). In diabetes groups, single-dose (65 mg/kg) STZ was administered intraperitoneally (i.p.). In Group DI/R, ischemia reperfusion was produced via 25 min of bilateral renal pedicle clamping followed by 48 h of reperfusion. In Group DI/R-DEX, 50 μg/kg dexmedetomidine was administered intraperitoneally 30 minutes before ischemia. Renal function, histology, apoptosis, the levels of TNF-α, IL-1β, and oxidative stress in diabetic kidney were determined. Moreover, expression of P38 mitogen-activated protein kinase (P38-MAPK), phosphorylated-P38-MAPK(p-P38-MAPK) and thioredoxin-interacting protein (TXNIP) were assessed. Results: The degree of renal I/R injury was significantly increased in DI/R group compared with S group and DS group. The levels of TNF-α, IL-1β, oxidative stress and apoptosis were found significantly higher in DI/R Group when compared with S Group and DS Group. The protein expression of p-P38-MAPK and TXNIP were significantly increased after I/R. All these changes were reversed by DEX treatment. Conclusion: The renoprotective effects of DEX-pretreatment which attenuates I/R-induced AKI were partly through inhibition of P38-MAPK activation and expression of TXINP in diabetic kidney.

http://ift.tt/2tuYVot

Fluorescent test accurately predicts leak of ischemic colon anastomosis in rats

Abstract Purpose: To investigate if fluorescein fluorescent test can predict dehiscence in a model of ischemic colonic anastomosis in rats. Methods: This experimental controlled trial randomly assigned 55 rats to four groups. Anastomoses were performed in non-ischemic colon segments (control group) and in ischemic colon segments measuring 1, 2 or 3 cm long (groups 1, 2 and 3, respectively). Fluorescein was injected and the tissues were examined under ultraviolet light. Seven days later, a second-look surgery was performed to check for the presence or absence of anastomosis dehiscence. Results: Twenty-four rats presented anastomotic dehiscence during the second-look surgery. Reticular and nonfluorescent patterns were significantly associated with the occurrence of anastomotic dehiscence. Fluorescein fluorescence had a sensitivity of 95.8%, specificity of 89.2%, positive predictive value of 88.4%, negative predictive value of 96.2%, and accuracy of 92.3% to predict anastomotic dehiscence. Conclusion: Fluorescein fluorescent test can accurately predict leak in a model of ischemic colonic anastomosis in rats.

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Impact of dexmedetomidine on amino acid contents and the cerebral ultrastructure of rats with cerebral ischemia-reperfusion injury

Abstract Purpose: To investigate the effects of dexmedetomidine (DEX) on amino acid contents and the cerebral ultrastructure of rats with cerebral ischemia-reperfusion injury (I/R). Methods: Thirty-six, male, Wistar rats were randomly divided into three groups: the sham operation group (group C), the ischemia-reperfusion group (group I/R), and the DEX group (group D). The middle cerebral artery occlusion model was prepared by the modified Longa method. The time of ischemia was 180 min, and 120 min after reperfusion, the amount of glutamate (Glu), and γ-aminobutyric acid (GABA) in the brain were measured, and the ultrastructure-level changes in the cerebral cortex were examined using electron microscopy. Results: Compared to group C, Glu contents in group D, and I/R significantly increased. Compared to group I/R, Glu contents in group D significantly decreased. Compared to group C, GABA contents in group D, and I/R significantly increased, and those in group D significantly increased, as compared to group I/R. The cerebral ultrastructure was normal in group C. Vacuolar degeneration in the plastiosome and nervous processes, was more critical than in group D. Vascular endothelial cells (VEC) were damaged. On the contrary, these changes in group D significantly improved. Conclusion: Dexmedetomidine is capable of decreasing glutamergic content, and increasing GABAergic content, in order to decrease the injury of the cerebral ultrastructure, following cerebral ischemia-reperfusion injury.

http://ift.tt/2sKBKJF

Animal model of continuous peritoneal lavage with vacuum peritoneostomy

Abstract Purpose: To establish and evaluate the feasibility of continuous peritoneal lavage with vacuum peritoneostomy in an animal model. Methods: Eight pigs aged 3-4 months, females, were anesthetized and submitted to laparotomy and installation of a continuous peritoneal lavage with vacuum peritoneostomy. The sta-bility of the system, the physiological effects of washing with NaCl 0.9% and the sys-tem clearance were evaluated. Results: Stability of vacuum peritoneostomy was observed, with no catheter leaks or obstructions and the clearance proved adequate, however, the mean volume of fluids aspirated by the peritoneostomy at the end of the experiment was higher than the volume infused by the catheters (p=0.02). Besides that, the animals presented a progressive increase in heart rate (p=0.04) and serum potassium (p=0.02). Conclusion: The continuous peritoneal lavage technique with vacuum peritoneostomy is feasible and presents adequate clearance.

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Comparative study of pain in women submitted to conventional laparoscopic cholecystectomy versus single-port laparoscopic cholecystectomy

Abstract Purpose: To evaluate postoperative pain in patients submitted to conventional laparoscopic cholecystectomy with four ports versus single-port laparoscopic cholecystectomy with only one port. Methods: Twenty-one patients were included in the conventional laparoscopic cholecystectomy group and 19 other patients in the single-port laparoscopic cholecystectomy group. A VAS was used for the assessment of postoperative pain at three time points. Differences were considered statistically significant when p<0.05. Results: Intergroup analysis showed no significant difference in VAS scores between the conventional laparoscopic cholecystectomy and single-port laparoscopic cholecystectomy groups at any of the time points studied. Conclusion: This study found no significant difference in postoperative pain between the two groups.

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Argon plasma versus electrofulguration in the treatment of anal and perianal condylomata acuminata in patients with acquired immunodeficiency virus

Abstract Purpose: To compare the effectiveness of anal and perianal condylomata treatment using argon plasma and electrofulguration. Methods: From January 2013 to April 2014, 37 patients with anal and perianal condylomata, who had been diagnosed through proctological examination, oncotic cytology, polymerase chain reaction (PCR) and histology, underwent treatment with argon plasma and electrofulguration. The perianal and anal regions were divided into two semicircles. Each semicircle was treated using one of the methods by means of simple randomization. Therapeutic sessions were repeated until all clinical signs of infection by HPV were eliminated. The patients were evaluated according to several variables like the genotype of HPV, HIV infection, oncological potential per genotype, oncotic cytology and histology. Results: Among all the variables studied, only immunosuppression due to HIV influenced the results, specifically when the fulguration method was used. There was no significant difference in effectiveness between argon and fulguration based on lesion relapse (p > 0.05). However, among HIV-positive patients, fulguration presented worse results, with a significant difference (p = 0.01). Conclusion: Regarding treatment of anal and perianal condylomata acuminata, comparison between applying fulguration and argon demonstrated that these methods were equivalent, but use of fulguration presented more relapses among HIV-positive patients.

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How does practice improve the skills of medical students during consecutive training courses?

Abstract Purpose: To follow-up the development of medical students in taking a stitch using two different bench models, and to assess their performance with regards to gender, handedness, prior recreational activities and interest in surgery. Methods: The study was performed during the compulsory basic (n=152) and the consecutive elective course (n=27). Students took simple interrupted stitches into synthetic and biopreprate models in the classroom and in the operating room. The time needed for that was measured and the quality was scored, using an OSATS (Objective Structured Assessment of Technical Skill) checklist that had been adapted to our training programs. Results: Students' performance improved both in time and quality during classes, over the course and compared basic to the elective course, too. No significant difference was found in relation to gender and handedness but certain recreational activities and special interest in surgery led to better results. Operating room environment had a slight negative effect on students' performance. Conclusion: The study could provide objective skill assessment, monitoring has revealed deficiencies and influencing factors. Objective feedback, valid and reliable assessment is important in teaching surgical skills. In addition it may contribute to higher surgical safety later on in the clinical practice.

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Smartphone Fundus Photography

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Fundus photography normally requires specialized fundus cameras that are not always available in all clinical settings. Here, a simple method to record ocular fundus images using a smartphone camera and a conventional high-plus handheld indirect ophthalmoscopy lens is described.

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A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer

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A protocol for the establishment of a genetically engineered mouse model of colorectal cancer by segmental adeno-cre infection and its surveillance via high-resolution colonoscopy is presented.

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Hypoxia-inducible tumour-specific promoters as a dual-targeting transcriptional regulation system for cancer gene therapy

Bita Javan and Majid Shahbazi

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Potential for a novel manganese porphyrin compound as adjuvant canine lymphoma therapy

Abstract

Purpose

Manganese porphyrins are redox-active drugs and superoxide dismutase mimics, which have been shown to chemosensitize lymphoma, a cancer which frequently occurs in dogs. This study aimed to identify critical information regarding the pharmacokinetics and toxicity of Mn(III) meso-tetrakis (N-n-butoxyetylpyridium-2-yl) porphyrin, (MnTnBuOE-2-PyP5+, MnBuOE) in dogs as a prelude to a clinical trial in canine lymphoma patients.

Methods

A single-dose pharmacokinetic (PK) study in normal dogs was performed to determine the plasma half-life (t 1/2) of MnBuOE. A dose reduction study was performed to establish the maximum tolerated dose (MTD) of MnBuOE. The safety and PK of a multi-dosing protocol was assessed.

Results

Peak plasma drug concentration occurred 30 min post-injection. The t 1/2 was defined as 7 h. MnBuOE induced an anaphylactic reaction and prolonged tachycardia. The MTD was defined as 0.25 mg/kg. The dogs were given MTD 3×/week for 2–3 weeks. The highest recorded tissue drug levels were in the lymph nodes (4–6 μM), followed by kidney and liver (2.5, 2.0 uM, respectively).

Conclusions

We obtained critical information regarding the PK and toxicity of MnBuOE in dogs. The acute drug reaction and tachycardia post-injection have not been described in other species and may be specific to canines. The high tissue drug levels in lymph nodes have not been previously reported. MnBuOE accumulation in lymph nodes has important implications for the utility of adjuvant MnBuOE to treat lymphoma. With MnBuOE lymph node accumulation, reduction in the dose and/or administration frequency could be possible, leading to reduced toxicity.



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The oncologic burden of hepatitis C virus infection: A clinical perspective

ABSTRACT

Chronic hepatitis C virus (HCV) infection affects millions of people worldwide and is associated with cancer. Direct-acting antivirals (DAAs) have changed HCV treatment paradigms, but little is known about the management of HCV infection in patients with cancer. The substantial burden of HCV infection and the inconclusive evidence regarding its detection and management in patients with cancer prompted the authors to review the literature and formulate recommendations. Patients for whom HCV screening is recommended included all patients with hematologic malignancies, hematopoietic cell transplantation candidates, and patients with liver cancer. There is a lack of consensus-based recommendations for the identification of HCV-infected patients with other types of cancer, but physicians may at least consider screening patients who belong to groups at heightened risk of HCV infection, including those born during 1945 through 1965 and those at high risk for infection. Patients with evidence of HCV infection should be assessed by an expert to evaluate liver disease severity, comorbidities associated with HCV infection, and treatment opportunities. DAA therapy should be tailored on the basis of patient prognosis, type of cancer, cancer treatment plan, and hepatic and virologic parameters. HCV-infected patients with cancer who have cirrhosis (or even advanced fibrosis) and those at risk for liver disease progression, especially patients with HCV-associated comorbidities, should have ongoing follow-up, regardless of whether there is a sustained virologic response, to ensure timely detection and treatment of hepatocellular carcinoma. HCV infection and its treatment should not be considered contraindications to cancer treatment and should not delay the initiation of an urgent cancer therapy. CA Cancer J Clin 2017. © 2017 American Cancer Society.



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Emerging Semitransparent Solar Cells: Materials and Device Design

Semitransparent solar cells can provide not only efficient power-generation but also appealing images and show promising applications in building integrated photovoltaics, wearable electronics, photovoltaic vehicles and so forth in the future. Such devices have been successfully realized by incorporating transparent electrodes in new generation low-cost solar cells, including organic solar cells (OSCs), dye-sensitized solar cells (DSCs) and organometal halide perovskite solar cells (PSCs). In this review, the advances in the preparation of semitransparent OSCs, DSCs, and PSCs are summarized, focusing on the top transparent electrode materials and device designs, which are all crucial to the performance of these devices. Techniques for optimizing the efficiency, color and transparency of the devices are addressed in detail. Finally, a summary of the research field and an outlook into the future development in this area are provided.

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Recent developments of semitransparent organic solar cells, dye-sensitized solar cells, and perovskite solar cells are reviewed with a focus on different device design, transparent top electrode materials and the corresponding device fabrication techniques. Key issues related to the optimization of the efficiency, color and transparency of the semitransparent photovoltaic devices are discussed in detail.



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A Comparative Study of Clinical Intervention and Interventional Photothermal Therapy for Pancreatic Cancer

Although nanoparticle-based photothermal therapy (PTT) has been intensively investigated recently, its comparative efficiency with any clinical cancer treatments has been rarely explored. Herein for the first time we report a systematic comparative study of clinical iodine-125 (125I) interstitial brachytherapy (IBT-125-I) and interventional PTT (IPTT) in an orthotopic xenograft model of human pancreatic cancer. IPTT, based on the nanoparticles composing of anti-urokinase plasminogen activator receptor (uPAR) antibody, polyethylene glycol (PEG), and indocyanine green (ICG) modified gold nanoshells (hereinafter uIGNs), is directly applied to local pancreatic tumor deep in the abdomen. In comparison to IBT-125-I, a 25% higher median survival rate of IPTT with complete ablation by one-time intervention has been achieved. The IPTT could also inhibit pancreatic tumor metastasis which can be harnessed for effective cancer immunotherapy. All results show that this IPTT is a safe and radical treatment for eradicating tumor cells, and may benefit future clinical pancreatic cancer patients.

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Gold nanoshells conjugated with anti-urokinase plasminogen activator receptor (uPAR) antibody, polyethylene glycol (PEG), and indocyanine green (ICG) were successfully synthesized. The synthesized nanomaterials are capable of actively targeting uPAR -overexpressing pancreatic tumors. In this study, we developed a novel interventional photothermal therapy method based on this nanomaterial, and demonstrated that this approach comprises a safe method for eradicating pancreatic tumor cells.



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Seronegative Autoimmune Hepatitis A Clinically Challenging Difficult Diagnosis

Autoimmune hepatitis (AIH) is a complex liver disease of unknown cause which results in immune-mediated liver injury with varied clinical presentations. Seronegative AIH follows a similar course to autoantibody-positive disease and diagnosis may be challenging. There are no single serologic tests of sufficient diagnostic specificity, and delay in appropriate treatment may lead to progression of the liver disease and liver failure. The revised conventional diagnostic criteria (RDC) scoring for AIH is complex and not routinely used in the clinical practice. The more recent simplified diagnostic criteria (SDC) scoring proposed by International Autoimmune Hepatitis Group in 2008 has wider application in routine practice facilitating the diagnosis of AIH with a specificity and sensitivity of ~90%. In this report, we describe a case of seronegative autoimmune hepatitis diagnosed using RDC. SDC score calculated in our case was 4 and was not diagnostic for AIH. We subsequently used the complex revised diagnostic criteria for definitive diagnosis. Some of the patients previously diagnosed as cryptogenic active hepatitis of unknown etiology probably had an unrecognized diagnosis of seronegative autoimmune hepatitis. SDC scoring may not be applicable in patients with seronegative autoimmune hepatitis. These patients should be reassessed by using RDC.

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MALDI-TOF-MS analysis in discovery and identification of serum proteomic patterns of ovarian cancer

Abstract

Background

Due to high mortality and lack of efficient screening, new tools for ovarian cancer (OC) diagnosis are urgently needed. To broaden the knowledge on the pathological processes that occur during ovarian cancer tumorigenesis, protein-peptide profiling was proposed.

Methods

Serum proteomic patterns in samples from OC patients were obtained using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF). Eighty nine serum samples (44 ovarian cancer and 45 healthy controls) were pretreated using solid-phase extraction method. Next, a classification model with the most discriminative factors was identified using chemometric algorithms. Finally, the results were verified by external validation on an independent test set of samples.

Results

Main outcome of this study was an identification of potential OC biomarkers by applying liquid chromatography coupled with tandem mass spectrometry. Application of this novel strategy enabled the identification of four potential OC serum biomarkers (complement C3, kininogen-1, inter-alpha-trypsin inhibitor heavy chain H4, and transthyretin). The role of these proteins was discussed in relation to OC pathomechanism.

Conclusions

The study results may contribute to the development of clinically useful multi-component diagnostic tools in OC. In addition, identifying a novel panel of discriminative proteins could provide a new insight into complex signaling and functional networks associated with this multifactorial disease.



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ALK -rearranged lung squamous cell carcinoma responding to alectinib: a case report and review of the literature

Abstract

Background

Although anaplastic lymphoma kinase (ALK) fusion genes are generally identified in lung adenocarcinoma patients, they are relatively rare in patients with squamous cell carcinoma (SqCC). Metastatic ALK-rearranged lung adenocarcinoma patients treated with ALK inhibitors demonstrate higher response rates, improved progression-free survival, and reduced toxicity relative to those treated with conventional chemotherapy regimens. However, the efficacy of treatment with ALK inhibitors in patients with ALK-rearranged lung SqCC remains unknown.

Case presentation

We discuss a 52-year-old Japanese-Brazilian woman without a history of smoking who was referred to our hospital for evaluation of severe left back pain and a left hilar mass observed on a chest radiograph. The patient was eventually diagnosed on the basis of computed tomography, pathological, and immunohistochemical findings as having Stage IV lung SqCC. First-line treatment with palliative radiotherapy and systemic chemotherapy with cisplatin plus vinorelbine was administered, but was not effective. ALK testing was subsequently performed, revealing positive ALK expression and gene rearrangement. Alectinib therapy was then initiated, which resulted in a gradual, but substantial reduction in tumor size.

Conclusions

To the best of our knowledge, this is the first case report to discuss the successful management of ALK-rearranged lung SqCC with alectinib. We propose that molecular testing for driver mutations should be considered in young patients with a light or no smoking history, even if the histological findings correspond with SqCC, and alectinib therapy represents a reasonable option in cases of ALK-rearranged lung SqCC.



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Direct Neuronal Reprogramming: Achievements, Hurdles, and New Roads to Success

Gascón et al. discuss key intrinsic molecular and metabolic hurdles that impact direct neuronal conversion and highlight ongoing progress and remaining challenges, with a particular focus on direct in vivo reprogramming.

http://ift.tt/2uu72Bx

Making HSCs on Demand: Looking Ahead

George Daley and Shahin Rafii's groups recently generated multilineage, serially engrafting hematopoietic stem cells (HSCs) from human pluripotent stem cells and endothelial cells, respectively, achieving an important research milestone for the field. We asked some experts in the field to reflect on the broader implications of these findings.

http://ift.tt/2tVtSov

The Evolving Roles of Human iPSC-Derived Cardiomyocytes in Drug Safety and Discovery

Nonclinical studies of drug effects with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide new possibilities for evaluating drug safety and efficacy. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) paradigm provides lessons from the cardiac field that also apply to drug studies with other stem cell-based assays.

http://ift.tt/2uuuoH4

Muscle Stem Cells Undergo Extensive Clonal Drift during Tissue Growth via Meox1-Mediated Induction of G2 Cell-Cycle Arrest

Currie and colleagues reveal a dramatic clonal drift of muscle stem cells during tissue growth, which is regulated at the G2 phase of the cell cycle via Meox1-dependent control of ccnb1. This contrasts with G0/G1 phase control evident in adult stem cells, indicating divergent modes of stem cell regulation.

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Lack of Immune Response to Differentiated Cells Derived from Syngeneic Induced Pluripotent Stem Cells

(Cell Stem Cell 12, 407–412; April 4, 2013)

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Retinoic Acid Puts Hematopoietic Stem Cells Back To Sleep

Dormant hematopoietic stem cells (dHSCs) display superior serial reconstitution capacity compared to active HSCs, although their role in normal hematopoiesis has not been thoroughly investigated. Recently in Cell, Cabezas-Wallscheid et al. (2017) demonstrate involvement of retinoic acid signaling in murine dHSCs for preservation of the HSC pool.

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Expanding the Tissue Toolbox: Deriving Colon Tissue from Human Pluripotent Stem Cells

Organoid technology holds great potential for disease modeling and regenerative medicine. In this issue of Cell Stem Cell, Múnera et al. (2017) establish the generation of pluripotent stem cell-derived colon organoids that upon transplantation in mice, strikingly resemble human colon, opening up avenues to study disease pathogenesis in human colon tissue.

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Lineage Tracing: Papers and Progress

This i3 is a data visualization based on the Cell Stem Cell tenth anniversary theme of lineage tracing. Using Scopus citations of Cell Stem Cell research papers, it illustrates both the evolution of the stem cell field and the way new research builds on work that came before. Users can navigate the graphic and the represented papers by stem cell type, organism, and author online at http://ift.tt/2uu6ZFR. To view this SnapShot, open or download the PDF.

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Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell Activity

Multiple cell populations, represented by distinct markers including Lgr5 and Bmi1, are capable of reconstituting the intestinal epithelium. Using comparative RNA-sequencing and single-cell transcriptomics, Yan et al. define Bmi1-GFP+ and Prox1+ cells as enteroendocrine lineage cells that possess intestinal stem cell activity during homeostasis and injury-induced regeneration.

http://ift.tt/2tVRjOB

Stem Cells: All that Is Solid Melts into Air

The intestinal epithelium displays great resilience, as several cell populations can replenish the stem cell pool upon damage. Two studies in Cell Stem Cell extend this capacity to enteroendocrine cells, addressing the molecular basis underlying cellular plasticity observed in the intestine and the identities of putative reserve stem cells.

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Modeling the Glomerular Filtration Barrier: Are You Kidney-ing Me?

Podocyte depletion drives kidney disease and kidney failure progression, but podocyte complexity at the glomerular filtration barrier is difficult to model in vitro. In Nature Biomedical Engineering, Musah et al. (2017) developed a multifluidic device with iPS-derived podocytes mimicking a functional glomerular filtration barrier that elevates standards for modeling glomerular diseases.

http://ift.tt/2tVLSiX

Generation of Human Hair Cells In Vitro: Is It All about How the Wnt Blows?

Screening for small molecules or drugs that can protect or restore mechanosensory hair cells has been hampered by limited cell numbers. In Nature Biotechnology, Koehler et al. (2017) have developed a human organoid-based approach using basic developmental principles to generate large numbers of bonafide hair cells in vitro.

http://ift.tt/2uucZ1g

The aCCR(2)ual of M2 Macrophages Provides Some Breathing Room

Lung tissue can robustly regenerate functional alveolar units after injury, but the mechanisms are unknown. Lechner et al. (2017) in this issue of Cell Stem Cell demonstrate that lung regeneration is facilitated by bone-marrow-derived myeloid cells that are recruited to the lung through a CCL2-CCR2 chemokine axis and by IL-13 expressing innate lymphoid cells.

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Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium-chain triglyceride ketogenic diet

Summary

Objective

The medium-chain triglyceride (MCT) ketogenic diet contains both octanoic (C8) and decanoic (C10) acids. The diet is an effective treatment for pharmacoresistant epilepsy. Although the exact mechanism for its efficacy is not known, it is emerging that C10, but not C8, interacts with targets that can explain antiseizure effects, for example, peroxisome proliferator-activated receptor-γ (eliciting mitochondrial biogenesis and increased antioxidant status) and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. For such effects to occur, significant concentrations of C10 are likely to be required in the brain.

Methods

To investigate how this might occur, we measured the β-oxidation rate of 13C-labeled C8 and C10 in neuronal SH-SY5Y cells using isotope-ratio mass spectrometry. The effects of carnitine palmitoyltransferase I (CPT1) inhibition, with the CPT1 inhibitor etomoxir, on C8 and C10 β-oxidation were also investigated.

Results

Both fatty acids were catabolized, as judged by 13CO2 release. However, C10 was β-oxidized at a significantly lower rate, 20% that of C8. This difference was explained by a clear dependence of C10 on CPT1 activity, which is low in neurons, whereas 66% of C8 β-oxidation was independent of CPT1. In addition, C10 β-oxidation was decreased further in the presence of C8.

Significance

It is concluded that, because CPT1 is poorly expressed in the brain, C10 is relatively spared from β-oxidation and can accumulate. This is further facilitated by the presence of C8 in the MCT ketogenic diet, which has a sparing effect upon C10 β-oxidation.



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Your Hands May Reveal the Struggle to Maintain Self-Control

It takes just a few seconds to choose a cookie over an apple and wreck your diet for the day. But what is happening during those few seconds while you make the decision?

In a new study, researchers watched in real time as people's hands revealed the struggle they were under to choose the long-term goal over short-term temptation. The work, forthcoming in Psychological Science, a journal of the Association for Psychological Science, represents a new approach to studying self-control.

In one key experiment, participants viewed pictures of a healthy and an unhealthy food choice on opposite sides of the top of a computer screen and moved a cursor from the center bottom to select one of the foods.

People who moved the cursor closer to the unhealthy treat (even when they ultimately made the healthy choice) later showed less self-control than did those who made a more direct path to the healthy snack.

"Our hand movements reveal the process of exercising self-control," said Paul Stillman, co-author of the study and postdoctoral researcher in psychology at The Ohio State University.

"You can see the struggle as it happens. For those with low self-control, the temptation is actually drawing their hand closer to the less-healthy choice."

The results may shed light on a scholarly debate about what's happening in the brain when humans harness willpower.

Stillman conducted the study with Melissa Ferguson, professor of psychology, and Danila Medvedev, a former undergraduate student, both from Cornell University.

The study involved several experiments. In one, 81 college students made 100 decisions involving healthy versus unhealthy food choices.

In each trial, they clicked a "Start" button at the bottom of the screen. As soon as they did, two images appeared in the upper-left and upper-right corners of the screen, one a healthy food (such as Brussels sprouts) and the other an unhealthy one (such as a brownie).

They were told to choose as quickly as possible which of the two foods would most help them meet their health and fitness goals. So there was a "correct" answer, even if they were tempted by a less healthy treat.

Before the experiment began, the participants were told that after they finished they would be given one of the foods they chose in the experiment. At the end, however, they could freely choose whether they wanted an apple or a candy bar.

The results showed that those who chose the candy bar at the end of the experiment – those with lower self-control – had tended to veer closer to the unhealthy foods on the screen.

"The more they were pulled toward the temptation on the computer screen, the more they actually chose the temptations and failed at self-control," Stillman said.

But for those with higher levels of self-control, the path to the healthy food was more direct, indicating that they experienced less conflict.

In two other studies, similar results occurred in a completely different scenario, in which college students could decide whether they would rather accept $25 today or $45 in 180 days. Those with lower levels of self-control had mouse trajectories that were clearly different from those with higher self-control, suggesting differences in how they were dealing with the decisions.

"This mouse-tracking metric could be a powerful new tool to investigate real-time conflict when people have to make decisions related to self-control," he said.

The findings also offer new evidence in a debate about how decision-making in self-control situations unfolds, Stillman said.

When the researchers mapped the trajectories people took with the cursor in the first experiment, they observed that most participants did not automatically start directly toward the unhealthy treat before abruptly switching course back to the healthy food. Rather, the trajectories appear curved, as if both the temptation and goal were competing from the beginning.

Why is that important?

Some researchers have argued that there are two systems in our brain that are involved in a self-control decision: one that's impulsive and a second that overcomes the impulses to exert willpower. But if that were the case, the trajectories seen in this study should look different than they do, Stillman said.

If dual systems underlie these choices, there should be a relatively straight line toward the unhealthy food while people are under the influence of the impulsive first system and then an abrupt change in direction toward the healthy food as the system in charge of self-control kicks in.

"That's not what we found," Stillman said. "Our results suggest a more dynamical process in which the healthy and unhealthy choices are competing from the very beginning in our brains and there isn't an abrupt change in thinking. That's why we get these curved trajectories."

Stillman said these results should help lead to a more accurate view of how our cognitive processes unfold to allow us to resist temptation.

All data and materials have been made publicly available via the Open Science Framework. The complete Open Practices Disclosure for this article is also online. This article has received badges for Open Data and Open Materials.



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