Surgical Performance: A Pathway to Excellence

No abstract available

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The Risk of Adverse Pregnancy Outcomes Following Nonobstetric Surgery During Pregnancy: Estimates From a Retrospective Cohort Study of 6.5 Million Pregnancies

Objective: The aim of this study was to estimate the risk of adverse birth outcomes for women who underwent nonobstetric surgery during pregnancy compared with those who did not. Background: Previous research suggests that nonobstetric surgery occurs during 1% to 2% of pregnancies. However, there is limited evidence quantifying risks to the mother or pregnancy of such surgery. Methods: We examined maternity admissions using hospital administrative data collected between April 1, 2002, and March 31, 2012, and identified pregnancies wherein nonobstetric surgery occurred. We used logistic regression models to determine the adjusted relative risk, attributable risk, and number needed to harm of nonobstetric surgical procedures for adverse birth outcomes. Results: We identified 6,486,280 pregnancies. In 47,628 of these pregnancies, nonobstetric surgery had occurred. We found that nonobstetric surgery during pregnancy was associated with a higher risk of adverse birth outcomes, although the attributable risk was generally low. We estimated that every 287 surgical operations were associated with 1 additional stillbirth, every 31 operations associated with 1 additional preterm delivery, every 39 operations associated with 1 additional low birth weight baby, every 25 operations associated with 1 additional caesarean section, and every 50 operations associated with 1 additional long inpatient stay. Conclusions: Although we have no means of disentangling the effect of the surgery from the effect of the underlying condition, we found that the risk associated with nonobstetric surgery was relatively low, confirming that surgical procedures during pregnancy are generally safe. We believe that our findings improve upon previous research, and are useful reference points for any discussion of risk with prospective patients.

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Mesorectal Excision With or Without Lateral Lymph Node Dissection for Clinical Stage II/III Lower Rectal Cancer (JCOG0212): A Multicenter, Randomized Controlled, Noninferiority Trial

Objective: The aim of the study was to confirm the noninferiority of mesorectal excision (ME) alone to ME with lateral lymph node dissection (LLND) in terms of efficacy. Background: Lateral pelvic lymph node metastasis is occasionally found in clinical stage II or III lower rectal cancer, and ME with LLND is the standard procedure in Japan. ME alone, however, is the international standard surgical procedure for rectal cancer. Methods: Eligibility criteria included histologically proven rectal cancer at clinical stage II/III; main lesion located in the rectum, with the lower margin below the peritoneal reflection; no lateral pelvic lymph node enlargement; Peformance Status of 0 or 1; and age 20 to 75 years. Patients were intraoperatively allocated to undergo ME with LLND or ME alone in a randomized manner. The primary endpoint was relapse-free survival, with a noninferiority margin for the hazard ratio of 1.34. Secondary endpoints included overall survival and local-recurrence-free survival. Analysis was by intention to treat. Results: In total, 701 patients were randomized to the ME with LLND (n = 351) and ME alone (n = 350) groups. The 5-year relapse-free survival in the ME with LLND and ME alone groups were 73.4% and 73.3%, respectively (hazard ratio: 1.07, 90.9% confidence interval 0.84–1.36), with a 1-sided P value for noninferiority of 0.0547. The 5-year overall survival, and 5-year local-recurrence-free survival in the ME with LLND and ME alone groups were 92.6% and 90.2%, and 87.7% and 82.4%, respectively. The numbers of patients with local recurrence were 26 (7.4%) and 44 (12.6%) in the ME with LLND and ME alone groups, respectively (P = 0.024). Conclusions: The noninferiority of ME alone to ME with LLND was not confirmed in the intent-to-treat analysis. ME with LLND had a lower local recurrence, especially in the lateral pelvis, compared to ME alone.

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In the Next Issue

No abstract available

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The Global Incidence of Appendicitis: A Systematic Review of Population-based Studies

Objective: We compared the incidence of appendicitis or appendectomy across the world and evaluated temporal trends. Summary Background Data: Population-based studies reported the incidence of appendicitis. Methods: We searched MEDLINE and EMBASE databases for population-based studies reporting the incidence of appendicitis or appendectomy. Time trends were explored using Poisson regression and reported as annual percent change (APC) with 95% confidence intervals (CI). APC were stratified by time periods and pooled using random effects models. Incidence since 2000 was pooled for regions in the Western world. Results: The search retrieved 10,247 citations with 120 studies reporting on the incidence of appendicitis or appendectomy. During the 21st century the pooled incidence of appendicitis or appendectomy (in per 100,000 person-years) was 100 (95% CI: 91, 110) in Northern America, and the estimated number of cases in 2015 was 378,614. The pooled incidence ranged from 105 in Eastern Europe to 151 in Western Europe. In Western countries, the incidence of appendectomy steadily decreased since 1990 (APC after 1989=−1.54; 95% CI: −2.22, −0.86), whereas the incidence of appendicitis stabilized (APC=−0.36; 95% CI: −0.97, 0.26) for both perforated (APC=0.95; 95% CI: −0.25, 2.17) and nonperforated appendicitis (APC=0.44; 95% CI: −0.84, 1.73). In the 21st century, the incidence of appendicitis or appendectomy is high in newly industrialized countries in Asia (South Korea pooled: 206), the Middle East (Turkey pooled: 160), and Southern America (Chile: 202). Conclusions: Appendicitis is a global disease. The incidence of appendicitis is stable in most Western countries. Data from newly industrialized countries is sparse, but suggests that appendicitis is rising rapidly.

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Phospholipid Capped Mesoporous Nanoparticles for Targeted High Intensity Focused Ultrasound Ablation

The mechanical effects of cavitation can be effective for therapy but difficult to control, thus potentially leading to off-target side effects in patients. While administration of ultrasound active agents such as fluorocarbon microbubbles and nanodroplets can locally enhance the effects of high intensity focused ultrasound (HIFU), it has been challenging to prepare ultrasound active agents that are small and stable enough to accumulate in tumors and internalize into cancer cells. Here, this paper reports the synthesis of 100 nm nanoparticle ultrasound agents based on phospholipid-coated, mesoporous, hydrophobically functionalized silica nanoparticles that can internalize into cancer cells and remain acoustically active. The ultrasound agents produce bubbles when subjected to short HIFU pulses (≈6 µs) with peak negative pressure as low as ≈7 MPa and at particle concentrations down to 12.5 µg mL⁻¹ (7 × 10⁹ particles mL⁻¹). Importantly, ultrasound agents are effectively uptaken by cancer cells without cytotoxic effects, but HIFU insonation causes destruction of the cells by the acoustically generated bubbles, as demonstrated by (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and lactate dehydrogenase assays and flow cytometry. Finally, it is showed that the HIFU dose required to effectively eliminate cancer cells in the presence of ultrasound agents causes only a small temperature increase of ≈3.5 °C.

High intensity focused ultrasound (HIFU) is promising for tissue ablation but suffers from off-target side effects. This work reports 100 nm mesoporous, hydrophobically modified silica nanoparticles coated with phospholipid monolayers, polyethylene glycol, and folate. These particles are uptaken into breast cancer cells without change in viability, but administration of HIFU with uptaken particles results in cell death.

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Increased matrix stiffness promotes tumor progression of residual hepatocellular carcinoma after insufficient heat treatment

Abstract

The aggravated behaviors of hepatocellular carcinoma (HCC) will occur after inadequate thermal ablation. However, its underlying mechanisms are not fully understood. Here, we assessed whether the increased matrix stiffness after thermal ablation could promote the progression of residual HCC. Heat-treated residual HCC cells were cultured on the tailorable 3D gel with different matrix stiffness simulating the changed physical environment after thermal ablation and then were explored the mechanical alterations of matrix stiffness on cell phenotypes. Increased stiffness was found to significantly promote the proliferation of the heat-treated residual HCC cells when the cells were cultured on stiffer versus soft supports, which was associated with stiffness-dependent regulation of extracellular-regulated-kinase (ERK) phosphorylation. Heat-exposed HCC cells were cultured on stiffer supports showed enhanced motility. More importantly, vitamin K1 reduced stiffness-dependent residual HCC cell proliferation via inhibiting ERK phosphorylation and suppressed the in vivo tumor growth, which was further enhanced by combining with sorafenib. Increased matrix stiffness promotes the progression of heat-treated residual HCC cells, proposing a new mechanism of an altered biomechanical environment after thermal ablation accelerating HCC development. Vitamin K1 plus sorafenib can reverse this pro-tumor effect.

This article is protected by copyright. All rights reserved.

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E-cadherin expression increases cell proliferation by regulating energy metabolism through NF-κB in AGS cells

Abstract

β-catenin is a central player in Wnt signaling, and activation of Wnt signaling is associated with cancer development. E-cadherin in complex with β-catenin mediates cell–cell adhesion, which suppresses β-catenin-dependent Wnt signaling. Recently, a tumor-suppressive role for E-cadherin has been reconsidered, as re-expression of E-cadherin was reported to enhance the metastatic potential of malignant tumors. To explore the role of E-cadherin, we established an E-cadherin-expressing cell line, EC96 cells, from AGS cells that featured undetectable E-cadherin expression and a high level of Wnt signaling. In EC96 cells, E-cadherin re-expression enhanced cell proliferation, although Wnt signaling activity was reduced. Subsequent analysis revealed that NF-κB activation and consequent c-myc expression might be involved in E-cadherin expression-mediated cell proliferation. To facilitate rapid proliferation, EC96 cells enhance glucose uptake and produce ATP using both mitochondria OXPHOS and glycolysis, whereas AGS cells utilize these mechanisms less efficiently. These events appeared to be mediated by NF-κB activation. Therefore, E-cadherin re-expression and subsequent induction of NF-κB signaling likely enhance energy production and cell proliferation.

This article is protected by copyright. All rights reserved.

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Implication of chemo-resistant memory T cells for immune surveillance in patients with sarcoma receiving chemotherapy

Abstract

Chemotherapy has improved the prognosis of patients with sarcomas. However, it may suppress anti-tumor immunity. Recently, we reported a novel CD8⁺ memory T cell population with a chemo-resistance property, "young memory" T (T_YM) cells. In this study, we investigated the proportion and function of T_YM cells in peripheral blood of healthy donors and sarcoma patients who received chemotherapy and those who did not. The proportion of T_YM cells was significantly decreased in patients compared with that in healthy donors.

In healthy donors, anti-EBV CTLs were induced using mixed lymphocyte peptide culture, from not only T_YM cells but also T_CM and T_EM cells. No CTLs directed to tumor-associated antigens were induced. In sarcoma patients who did not receive chemotherapy, in addition to anti-EBV CTLs, CTLs directed to the tumor-associated antigen PBF were induced from T_YM, T_CM and T_EM cells. In sarcoma patients who received chemotherapy, EBV-specific CTLs were induced from T_YM cells but were hardly induced from T_EM cells. Interestingly, CTLs directed to the anti-tumor-associated antigen PBF were induced from T_YM cells but not from the T_CM and T_EM cells in sarcoma patients who received chemotherapy. The findings suggest that T_YM cells are resistant to chemotherapy and can firstly recover from the nadir. T_YM cells might be important for immunological memory, especially in sarcoma patients receiving chemotherapy.

This article is protected by copyright. All rights reserved.

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Angiogenic, inflammatory and immunologic markers in predicting response to sunitinib in metastatic renal cell carcinoma

Abstract

The objective of this prospective study was to identify baseline angiogenic and inflammatory markers in serum as well as the baseline levels of immune cells in whole blood to predict progression free survival in patients with metastatic renal cell carcinoma treated with sunitinib. Blood samples were collected at baseline in all 90 patients to analyse serum angiogenic and inflammatory marker together with peripheral blood immunological marker. The association between each marker and sunitinib efficacy was analyzed. Univariate and multivariate Cox proportional model analyses were used to assess the correlation between those markers with survival. Baseline levels of interleukin-6, -8, high sensitivity C-reactive protein, and myeloid-derived suppressor cells were significantly higher in patients who progressed when compared with those with clinical benefit. Analysis by the Cox regression model showed that baseline interleukin-8, high sensitivity C-reactive protein and percentage of T helper type 1 cells were significantly associated with progression free survival in univariate analysis. Furthermore, in multivariate analysis, those three markers were independent indices to predict progression free survival.

In conclusion, angiogenic (interleukin-8), inflammatory (interleukin-6, high sensitivity C-reactive), and immunologic (myeloid-derived suppressor cells, percentage of T helper type 1 cells) markers at baseline would predict response to sunitinib therapy and/or disease progression in patients with metastatic renal cell carcinoma.UMIN Clinical Trials Registry UMIN000009622

This article is protected by copyright. All rights reserved.

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Advance MR imaging in sports-related concussion and mild traumatic brain injury – ready for clinical use?

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Long-lasting contribution of dopamine in the nucleus accumbens core, but not dorsal lateral striatum, to sign-tracking

Abstract

The attribution of incentive salience to reward-paired cues is dependent on dopamine release in the nucleus accumbens core. These dopamine signals conform to traditional reward-prediction error signals and have been shown to diminish with time. Here we examined if the diminishing dopamine signal in the nucleus accumbens core has functional implications for the expression of sign-tracking, a Pavlovian conditioned response indicative of the attribution of incentive salience to reward-paired cues. Food-restricted male Sprague-Dawley rats were trained in a Pavlovian paradigm in which an insertable lever predicted delivery of food reward in a nearby food cup. After 7 or 14 training sessions, rats received infusions of saline, the dopamine antagonist flupenthixol, or the GABA agonists baclofen and muscimol into the nucleus accumbens core or the dorsal lateral striatum. Dopamine antagonism within the nucleus accumbens core attenuated sign-tracking, whereas reversible inactivation did not affect sign-tracking but increased non-specific food cup checking behaviors. Neither drug in the dorsal lateral striatum affected sign-tracking behavior. Critically, extended training did not alter these effects. Though extended experience with an incentive stimulus may reduce cue-evoked dopamine in the nucleus accumbens core, this does not remove the dependence on dopamine in this region to promote Pavlovian cue approach nor result in the recruitment of dorsal lateral striatal systems for this behavior. These data support the notion that dopamine within the mesoaccumbal system, but not the nigrostriatal system, contributes critically to incentive motivational processes independent of the length of training.

This article is protected by copyright. All rights reserved.

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Porous Silicon Nanoparticle Delivery of Tandem Peptide Anti-Infectives for the Treatment of Pseudomonas aeruginosa Lung Infections

There is an urgent need for new materials to treat bacterial infections. In order to improve antibacterial delivery, an anti-infective nanomaterial is developed that utilizes two strategies for localization: i) a biodegradable nanoparticle carrier to localize therapeutics within the tissue, and ii) a novel tandem peptide cargo to localize payload to bacterial membranes. First, a library of antibacterial peptides is screened that combines a membrane-localizing peptide with a toxic peptide cargo and discovers a tandem peptide that displays synergy between the two domains and is able to kill Pseudomonas aeruginosa at sub-micromolar concentrations. To apply this material to the lung, the tandem peptide is loaded into porous silicon nanoparticles (pSiNPs). Charged peptide payloads are loaded into the pores of the pSiNP at ≈30% mass loading and ≈90% loading efficiency using phosphonate surface chemistry. When delivered to the lungs of mice, this anti-infective nanomaterial exhibits improved safety profiles over free peptides. Moreover, treatment of a lung infection of P. aeruginosa results in a large reduction in bacterial numbers and markedly improves survival compared to untreated mice. Collectively, this study presents the selection of a bifunctional peptide-based anti-infective agent and its delivery via biodegradable nanoparticles for application to an animal model of lung infection.

Antibiotic treatment can benefit from strategies to improve localization. A membrane-localizing anti-infective peptide is delivered via biodegradable porous silicon nanoparticles to decrease bacterial numbers in a lung infection model. It is believed that these tandem peptide nanomaterials offer an approach to building anti-infectives that could complement existing small-molecule antibiotic treatments.

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Promoting Cell Migration in Tissue Engineering Scaffolds with Graded Channels

Ideal bone scaffolds having good biocompatibility, good biodegradability, and beneficial mechanical properties are the basis for bone tissue engineering. Specifically, cell migration within 3D scaffolds is crucial for bone regeneration of critical size defects. In this research, hydroxyapatite scaffolds with three different types of architectures (tortuous, parallel, and graded channels) are fabricated using the freeze-casting (ice-templating) method. While most studies promote cell migration by chemical factors, it can be greatly enhanced by introducing only graded channels as compared with tortuous or parallel channels. The results provide insights and guidance in designing novel scaffolds to enhance cell migration behavior for bone tissue regeneration.

Cell migration within 3D scaffolds is crucial for bone regeneration at critical size defects. Here, hydroxyapatite scaffolds with different microstructures are fabricated. Cell migration is greatly promoted within the scaffolds with graded channels comparing with those having tortuous or parallel channels. The results provide new insights and guidance for designing novel scaffolds to regulate cell migration behavior for bone regeneration.

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Enzyme Prodrug Therapy Engineered into Electrospun Fibers with Embedded Liposomes for Controlled, Localized Synthesis of Therapeutics

Enzyme prodrug therapy (EPT) enables localized conversion of inert prodrugs to active drugs by enzymes. Performance of EPT necessitates that the enzyme remains active throughout the time frame of the envisioned therapeutic application. β-glucuronidase is an enzyme with historically validated performance in EPT, however it retains its activity in biomaterials for an insufficiently long period of time, typically not exceeding 7 d. Herein, the encapsulation of β-glucuronidase in liposomal subcompartments within poly(vinyl alcohol) electrospun fibers is reported, leading to the assembly of biocatalytically active materials with activity of the enzyme sustained over at least seven weeks. It is further shown that liposomes provide the highly beneficial stabilization of the enzyme when incubated in cell culture media. The assembled biocatalytic materials successfully produce antiproliferative drugs (SN-38) using externally administered prodrugs (SN-38-glucuronide) and effectively suppress cell proliferation, with envisioned utility in the design of cardiovascular grafts.

β-glucuronidase is an enzyme with historically validated performance in enzyme prodrug therapy, however β-glucuronidase retains its activity in biomaterials for an insufficiently long period of time, typically not exceeding 7 d. Here, encapsulation of β-glucuronidase in liposomal subcompartments within electrospun fibers affords a highly stable preparation of biocatalytically active materials with activity of the enzyme sustained over at least seven weeks.

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Melt Electrospinning Writing of Poly-Hydroxymethylglycolide-co-ε-Caprolactone-Based Scaffolds for Cardiac Tissue Engineering

Current limitations in cardiac tissue engineering revolve around the inability to fully recapitulate the structural organization and mechanical environment of native cardiac tissue. This study aims at developing organized ultrafine fiber scaffolds with improved biocompatibility and architecture in comparison to the traditional fiber scaffolds obtained by solution electrospinning. This is achieved by combining the additive manufacturing of a hydroxyl-functionalized polyester, (poly(hydroxymethylglycolide-co-ε-caprolactone) (pHMGCL), with melt electrospinning writing (MEW). The use of pHMGCL with MEW vastly improves the cellular response to the mechanical anisotropy. Cardiac progenitor cells (CPCs) are able to align more efficiently along the preferential direction of the melt electrospun pHMGCL fiber scaffolds in comparison to electrospun poly(ε-caprolactone)-based scaffolds. Overall, this study describes for the first time that highly ordered microfiber (4.0–7.0 µm) scaffolds based on pHMGCL can be reproducibly generated with MEW and that these scaffolds can support and guide the growth of CPCs and thereby potentially enhance their therapeutic potential.

Fabrication of highly ordered microfiber scaffolds for cardiac tissue engineering is achieved by melt electrospinning writing of a hydroxyl-functionalized polyester. These scaffolds can support and guide the growth of cardiac progenitor cells while recapitulating the mechanical environment of the native cardiac tissue. This approach provides a framework for the development of therapeutically viable in vitro engineered cardiac tissues.

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Optimal treatment for lumbar spinal stenosis: an update.

Purpose of review: Our review of current literature within the past 12-24 months for the treatment of lumbar spinals stenosis (LSS) serves to update providers on recent advances and comparisons regarding therapy spanning lifestyle modification, pharmacologic therapy, minimally invasive interventions, and surgical interventions. Recent findings: Current literature supporting the inclusion of physical therapy and gabapentin/pregabalin within an initial treatment regimen have been positive. A recent randomized, double-blinded clinical trial of adding calcitonin to epidural steroid injections have shown improvement in pain and function up to 1 year. The minimally invasive lumbar decompression (mild) procedure is showing ongoing beneficial results in pain and function. Spinal cord stimulation (SCS) may have a role for select patients with lumbar spinal stenosis. Finally, the benefits of surgical treatment versus nonsurgical treatment is ultimately inconclusive because of the nature of data collection, inconsistencies with the clinical definition of LSS, and a lack of standardized treatment guidelines. Summary: Our review of current research demonstrates there is a positive role for the current conservative therapies, with favorable results for interventions such as minimally invasive decompression and SCS. Pharmacologic interventions such as systemic prostaglandin analogues and epidural agents such as calcitonin demonstrate early promise, but need to undergo additional safety testing and confirmatory trials. Further long-term research with validated, objective measurements for the aforementioned treatments are needed to draw any definitive conclusions for clinical practice. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Regional blocks carried out during general anesthesia or deep sedation: myths and facts.

Purpose of review: More patients will accept regional blocks if these are performed during sedation or general anesthesia. This review discusses regional anesthesia in sedated or anesthetized patients. Recent findings: As complications of regional blocks are rare, regional anesthesia can be considered aswell-tolerated. Awake patients will notice only a minority of needle-to-nerve contacts, that renders the notion of a 'live monitor' obsolete. Using high-resolution ultrasound, the needle can be advanced to an extraepineural position for injection, thus strictly avoiding needle-to-nerve contact or intraepineural injection of local anesthetic. Rare cases of intoxication manifest more immediately when the patient is awake but some general anesthesia drugs reduce the seizure-inducing potency of local anesthetics, and hemodynamic signs of intoxication are also detectable under general anesthesia, allowing for faster cardiopulmonary resuscitation as the patient is anesthetized already. Summary: With the use of ultrasound guidance in skilled hands, it is a reasonable option to perform neuraxial and peripheral regional blocks in sedated or anesthetized patients. Performing the procedure safely and effectively requires an adequate level of experience with the specific block technique in question. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Clinical Snippets

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Melanin pigmentation and melanoma

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Issue Information

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Impaired corticomuscular coherence during isometric elbow flexion contractions in human with cervical Spinal Cord Injury

Abstract

After spinal cord injury (SCI), the reorganization of the neuromuscular system leads to increased antagonist muscles' co-activation – i.e., increased antagonist vs. agonist muscles activation ratio – during voluntary contractions. Increased muscle co-activation is supposed to result from reduced cortical influences on spinal mechanisms inhibiting antagonist muscles. The assessment of the residual interactions between cortical and muscles activity with corticomuscular coherence (CMC) in participants with SCI producing different force levels may shed new lights on the regulation of muscle co-activation.

To this aim, we compared the net joint torque, the muscle co-activation and the CMC ˜10 Hz and ˜20 Hz with both agonist and antagonist muscles in participants with SCI and healthy participants performing actual isometric elbow flexion contractions at 3 force levels. For all participants, overall CMC and muscle co-activation decreased with the increase of the net joint torque but only CMC ~10 Hz was correlated with muscle co-activation. Participants with SCI had greater muscle co-activation and lower CMC ~10 Hz, at the highest force levels.

These results emphasize the importance of CMC as a mechanism that could take part in the modulation of muscle co-activation to maintain a specific force level. Lower CMC ~10 Hz in SCI participants may reflect the decreased cortical influence on spinal mechanisms leading to increased muscle co-activation. Though, plasticity of the corticomuscular coupling seems to be preserved after SCI to modulate the force level. Clinically, the CMC may efficiently evaluate the residual integrity of the neuromuscular system after SCI and the effects of rehabilitation.

This article is protected by copyright. All rights reserved.

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Does transcranial electrical stimulation enhance corticospinal excitability of the motor cortex in healthy individuals? A systematic review and meta-analysis

Abstract

Numerous studies have explored the effects of transcranial electrical stimulation (tES) – including anodal transcranial direct current stimulation (a-tDCS), cathodal transcranial direct current stimulation (c-tDCS), transcranial alternative current stimulation (tACS), transcranial random noise stimulation (tRNS) and transcranial pulsed current stimulation (tPCS) – on corticospinal excitability (CSE) in healthy populations. However, the efficacy of these techniques and their optimal parameters for producing robust results have not been studied. Thus, the aim of this systematic review was to consolidate current knowledge about the effects of various parameters of a-tDCS, c-tDCS, tACS, tRNS and tPCS on the CSE of the primary motor cortex (M1) in healthy people. Leading electronic databases were searched for relevant studies published between January 1990 and February 2017; 126 articles were identified, and their results extracted and analysed using RevMan software. The meta-analysis showed that a-tDCS application on the dominant side significantly increases CSE (P < 0.01), and that the efficacy of a-tDCS is dependent on current density and duration of application. Similar results were obtained for stimulation of M1 on the non-dominant side (P = 0.003).The effects of a-tDCS reduce significantly after 24 hours (P = 0.006). Meta-analysis also revealed significant reduction in CSE following c-tDCS (P <0.001) and significant increases after tRNS (P = 0.03) and tPCS (P = 0.01). However, tACS effects on CSE were only significant when the stimulation frequency was ≥140Hz. The present review provides evidence that tES has substantial effects on CSE in healthy individuals for a range of stimulus parameters.

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Strategies for building a successful ultrasound guided FNA practice in department of pathology—Experience at a university hospital

Abstract

Introduction

Although pathology services focused on fine needle aspiration (FNA) biopsy of superficial palpable masses with on-site cytological evaluation are available in a wide range of clinical and academic settings, the addition of ultrasound (US) guidance into FNA practice by a cytopathologist group can be challenging. An US-FNA service provided by a cytopathologist in the department of Pathology is a relatively new practice in the field of medicine. This report summarizes our experience and strategies in achieving this objective and our successful preliminary results.

Materials and Methods

The US-FNA service includes (1) an FNA procedure to be performed by a cytopathologist under US guidance; (2) onsite adequacy evaluation and diagnosis to be done by the same cytopathologist; and immediate patient consultation and sample triaging carried out by the same cytopathologist in an FNA suite within the department of Pathology. The FNA suite including a procedure room equipped with a portable US machine, an exam/procedure table, a mobile cabinet with FNA supplies, a counter with sink, and a reception room with waiting area is set-up.

Results

The establishment of the US-FNA service is successful. There is an incremental growth of the service over the first 8 months. Among the 114 cases performed during the first 8 months, the case type distribution is shown to be 50% thyroid nodules, 33% lymph nodes, 5.5% salivary gland masses, 3.5% breast masses, and 8% soft tissue masses.

Conclusions

The authors' initial 8 months experience and strategies in setting up a new US-FNA practice in a new institution are discussed to highlight obstacles encountered and approaches that promoted the successful establishment of a new service. A conservative approach, focusing on building partnerships with existing clinical services, can be successfully implemented in most institutions, if appropriate strategies are applied. The main strategy is to ensure that the best interests of patients remain the primary focus and that everything possible is done to improve the quality and effectiveness of patient care by providing the best possible diagnostic US-FNA service, to enable optimal clinical management.

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Isolation and characterization of Arctic microorganisms decomposing bioplastics

The increasing amount of plastic waste causes significant environmental pollution. In this study, screening of Arctic microorganisms which are able to degrade bioplastics was performed. In total, 313 microorga...

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Quality evaluation of Alpinia oxyphylla after Aspergillus flavus infection for storage conditions optimization

In the storage of Alpinia oxyphylla, growth of mildew (especially toxic fungi, such as Aspergillus flavus) is a potential safety risk. Few reports have investigated how A. oxyphylla storage conditions impact mold...

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Call for a European Paediatric Association/Union of National European Paediatric Societies and Associations Survey on National Child Health Care Services for European Children with Malignancies

Highly specialized pediatric centers are needed for the diagnosis and treatment of rare but life-threatening conditions, including malignant diseases, because children with these disorders require complex diagnostic procedures and high-end therapeutic interventions, such as stem cell transplantation.1,2 Centralization of subspecialty care is instrumental to ensure the quality of care that correlates with experience and consequently with the number of rare cases diagnosed and treated, as is seen in pediatric oncology, as well as in maternal and neonatal care.

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What Happens to Blood Glucose Concentrations After Oral Treatment for Neonatal Hypoglycemia?

To determine the change in blood glucose concentration after oral treatment of infants with hypoglycemia in the first 48 hours after birth.

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Examining the Role of the Pediatric Emergency Department in Reducing Unintended Adolescent Pregnancy

To determine pregnancy risk and receptiveness to emergency department (ED)-based pregnancy prevention interventions among adolescents accessing care in the ED.

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Validity and Reliability of the Brazilian Version of the Weight Control Behaviors Scale

To develop and validate the weight-control behaviors (WCBs) scale and to evaluate its psychometric properties.

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Prostaglandin E1-Induced Periostitis and Reversibility with Discontinuation

A 4.1 kg full term infant with a known diagnosis of hypoplastic left heart syndrome was admitted to our pediatric intensive care unit after birth. Prostaglandin E1 (PGE1) infusion at 0.03 μg/kg/min was initiated immediately and continued thereafter for a prolonged period. He was listed for heart transplantation because of persistent poor right ventricle function and significant atrio-ventricular valve regurgitation. He underwent pulmonary arteries band placement to prevent excessive pulmonary blood flow and worsening heart failure.

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Treatment and Nontreatment of the Patent Ductus Arteriosus: Identifying Their Roles in Neonatal Morbidity

In this volume of The Journal, Bixler et al report their study of 61 520 infants (delivered before 31 weeks' gestation) in the Pediatrix Clinical Data Warehouse; they found that both the incidence of patent ductus arteriosus (PDA) reported and the number of infants receiving PDA treatment (either medical or surgical) declined significantly between 2006 and 2015.1 Their findings are similar to the results reported by Lokku et al from the Canadian Neonatal Network and by Hagadorn et al from the Pediatric Hospital Information System database.

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Neurodevelopmental Profiles of Children with Congenital Heart Disease at School Age

To assess 6-year neurodevelopmental outcomes in a current cohort of children with congenital heart disease (CHD) who underwent cardiopulmonary bypass surgery (CPB), and to determine risk factors for adverse outcomes.

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Collagen triple helix repeat containing-1 negatively regulated by microRNA-30c promotes cell proliferation and metastasis and indicates poor prognosis in breast cancer

Abstract

Background

Collagen triple helix repeat containing-1 (CTHRC1), which was firstly identified overexpressed in the adventitia and neointima of injured rat arteries, could inhibit collagen expression and increase cell migration. It was then found to be ubiquitously expressed in numerous cell types such as fibroblasts and smooth muscle cells, and aberrantly up-regulated in several malignant tumors. However, the functional role of CTHRC1 and its related mechanism in breast cancer still remains unclear.

Methods

CTHRC1 expressions in breast cancer tissues and cells were assessed by qRT-PCR, western blot and immunohistochemistry. The relative expression level of miR-134, miR-155, miR-30c and miR-630 in breast cancer cells respectively was detected by qRT-PCR. Wild type (Wt) and Mutant type (Mut) CTHRC1 3'UTR sequences were cloned into a psi-CHECK2 reporter vector, and the relative luciferase activity was detected by dual-luciferase reporter assay in indicated cells. The effect of ectopic expression of miR-30c or gain and loss of CTHRC1 on cell viability, cell proliferation, cell cycle progression and apoptosis, cell invasion and migration was respectively detected by CCK-8 assay, colony formation assay, flow cytometry analysis, transwell invasion/migration assay. Protein levels of β-catenin, active β-catenin, normal and phosphorylated form of GSK-3β were detected by western blot in indicated cells. Immunofluorescence staining of β-catenin was performed to observe nuclear localization.

Results

We found CTHRC1 was frequently up-regulated in human breast cancer cells and tissues. Then our cohort study and further meta-analysis validated high expression of CTHRC1 was associated with aggressive clinicopathological features and poor clinical outcome of breast cancer patients. In addition, CTHRC1 promoted cell proliferation, invasion and migration and suppressed cell apoptosis in breast cancer, which might be by activating GSK-3β/β-catenin signaling and inhibiting Bax/Caspase-9/Caspase-3 signaling respectively; and these biological functions of CTHRC1 could be directly negatively regulated by miR-30c.

Conclusion

Taken together, we identified the role of miR-30c/CTHRC1 axis in breast cancer progression and demonstrated CTHRC1 may serve as a prognostic biomarker and therapeutic target for breast cancer.

http://ift.tt/2tLGc7Z

Midwives’ personal use of complementary and alternative medicine (CAM) influences their recommendations to women experiencing a post-date pregnancy

Publication date: Available online 11 July 2017
Source:Women and Birth
Author(s): Lyndall Mollart, Virginia Skinner, Jon Adams, Maralyn Foureur
Complementary and Alternative Medicine (CAM) have increasingly been used by pregnant women with a steady rise in interest by midwives. Literature describing CAM and self-help options midwives recommend to women experiencing a post-date pregnancy is sparse. This study aimed to investigate if Australian midwives' personal CAM use impacts on discussions and recommendations of CAM/Self-help strategies.Methodology/designA survey of a national midwifery association midwifery members (n=3,552) was undertaken at a midwifery conference (October 2015) and via e-bulletins (November 2015–March 2016). The self-administered survey included questions on what self-help and CAM strategies midwives discuss and recommend to women with a post-date pregnancy, midwives' confidence levels on discussing or recommending CAM, midwives' own personal use of CAM.FindingsA total of 571 registered midwives completed the survey (16%). Demographics (age, years as a midwife, state of residence) reflected Australian midwives and the midwifery association membership. Most respondents discuss (91.2%) and recommend (88.6%) self-help/CAM strategies to women with a post-date pregnancy. The top five CAM recommended were Acupuncture (65.7%), Acupressure (58.1%), Raspberry Leaf (52.5%), Massage (38.9%) and Hypnosis/Calmbirthing/Hypnobirthing (35.7%). Midwives were more likely to discuss strategies if they personally used CAM (p<.001), were younger (p<.001) or had worked less years as midwives (p=.004). Midwives were more likely to recommend strategies if they used CAM in their own pregnancies (p=.001).ConclusionMidwives' personal use of CAM influenced their discussions and recommendations of CAM/self-help strategies to women experiencing a post-date pregnancy. This study has implications for inclusion of CAM in midwifery education curricula.



http://ift.tt/2ugywOa

Fear of childbirth in primiparous Italian pregnant women: The role of anxiety, depression, and couple adjustment

Publication date: Available online 11 July 2017
Source:Women and Birth
Author(s): Sara Molgora, Valentina Fenaroli, Laura Elvira Prino, Luca Rollè, Cristina Sechi, Annamaria Trovato, Laura Vismara, Barbara Volpi, Piera Brustia, Loredana Lucarelli, Renata Tambelli, Emanuela Saita
BackgroundThe prevalence of fear of childbirth in pregnant women is described to be about 20–25%, while 6–10% of expectant mothers report a severe fear that impairs their daily activities as well as their ability to cope with labour and childbirth. Research on fear of childbirth risk factors has produced heterogeneous results while being mostly done with expectant mothers from northern Europe, northern America, and Australia.AimsThe present research investigates whether fear of childbirth can be predicted by socio-demographic variables, distressing experiences before pregnancy, medical-obstetric factors and psychological variables with a sample of 426 Italian primiparous pregnant women.MethodsSubjects, recruited between the 34th and 36th week of pregnancy, completed a questionnaire packet that included the Wijma Delivery Expectancy Questionnaire, the Edinburgh Postnatal Depression Scale, the State-Trait Anxiety Inventory, the Dyadic Adjustment Scale, the Multidimensional Scale of Perceived Social Support, as well as demographic and anamnestic information. Fear of childbirth was treated as both a continuous and a dichotomous variable, in order to differentiate expectant mothers as with a severe fear of childbirth.FindingsResults demonstrate that anxiety as well as couple adjustment predicted fear of childbirth when treated as a continuous variable, while clinical depression predicted severe fear of childbirth.ConclusionsFindings support the key role of psychological variables in predicting fear of childbirth. Results suggest the importance of differentiating low levels of fear from intense levels of fear in order to promote adequate support interventions.



http://ift.tt/2uPApOZ

Conditional PAI-1 deletion in the endothelial compartment has no beneficial effect on radiation-induced whole-lung damage in mice

Radiation pneumonitis and radiation-induced lung fibrosis are common side effects of thoracic tumor treatment. Mechanisms of radiation-induced lung damage include breakdown of the alveolar-capillary barrier and endothelial activation. Plasminogen activator inhibitor type 1 (PAI-1) has been identified as an interesting therapeutic target against lung fibrosis by knockout of the PAI-1 gene or pharmaceutical inhibition of PAI-1. Our aim was to investigate whether the endothelial pool of PAI-1 plays a role in the development of radiation-induced lung damage, as previously demonstrated in the intestine.

http://ift.tt/2u6qCGK

A prospective randomized study of radiation dose escalation with combined proton-photon therapy for benign meningiomas

Fractionated radiotherapy is commonly used to treat recurrent or subtotally resected benign meningiomas (BM). This randomized controlled trial evaluates the role of dose escalation for BM and does not support a benefit with higher radiation dose within the dose range evaluated of 55.8 Gy(RBE) vs. 63 Gy(RBE). Twenty percent of the cohort incurred a cerebrovascular accident, emphasizing the importance of long-term surveillance for late toxicities.

http://ift.tt/2u6Wg79

Radiation-Induced Large Vessel Cerebral Vasculopathy in Pediatric Patients with Brain Tumors Treated with Proton Radiotherapy

The purpose of this research is to evaluate the incidence, time to development, imaging patterns, risk factors, and clinical significance of large vessel cerebral vasculopathy in pediatric patients with brain tumors treated with proton radiotherapy.

http://ift.tt/2sOpkfq

Interrater agreement in visual scoring of neonatal seizures based on majority voting on a web-based system: the Neoguard EEG database

http://ift.tt/2tGLnId

Pathologic Findings in Breast, Fallopian Tube and Ovary Specimens in non-BRCA Hereditary Breast and/or Ovarian Cancer Syndromes: A Study of 18 Patients with Deleterious Germline Mutations in RAD51C, BARD1, BRIP1, PALB2, MUTYH or CHEK2

Germline BRCA mutations account for a significant proportion of genetic/familial risk of breast and ovarian cancer (GBOC) susceptibility, but a broader spectrum of GBOC susceptibility genes has emerged in recent years. Genotype to phenotype correlations are known for some established forms of GBOC, however whether such correlations exist for less common GBOC variants is unclear. We reviewed our institution's experience with non-BRCA GBOC, looking specifically for trends in pathologic and clinical features.

http://ift.tt/2uP00Yr

Malignant mesenchymal neoplasms of the dermis and subcutis mimicking benign lesions: a case-based review

Abstract

In this short review, malignant mesenchymal neoplasms of the dermis and subcutis mimicking benign lesions and their differential diagnoses are discussed. These include plaque-like dermatofibrosarcoma protuberans, superficial low-grade fibromyxoid sarcoma, low-grade superficial malignant peripheral nerve sheath tumour, epithelioid sarcoma, pseudomyogenic haemangioendothelioma, Kaposi sarcoma mimicking cavernous haemangioma and benign lymphangioendothelioma, and rare forms of angiosarcoma mimicking a benign vascular lesion.

http://ift.tt/2tGkLGY

Entinostat neutralizes myeloid derived suppressor cells and enhances the antitumor effect of PD-1 inhibition in murine models of lung and renal cell carcinoma

Purpose: Recent advances in immunotherapy highlight the antitumor effects of immune- checkpoint inhibition despite a relatively limited subset of patients receiving clinical benefit. The selective class I histone deacetylase inhibitor (HDACi) entinostat has been reported to have immunomodulatory activity including targeting of immune suppressor cells in the tumor microenvironment. Thus, we decided to assess whether entinostat could enhance anti-PD-1 treatment and investigate those alterations in the immunosuppressive tumor microenvironment that contribute to the combined anti-tumor activity. <p>Experimental design: We utilized syngeneic mouse models of lung (LLC) and renal cell (RENCA) carcinoma, and assessed immune correlates, tumor growth and survival following treatment with entinostat (5 or 10 mg/kg, P.O.) and a PD-1 inhibitor (10 and 20 mg/kg, s.c.).</p> <p>Results: Entinostat enhanced the antitumor effect of PD-1 inhibition in two syngeneic mouse tumor models by reducing tumor growth and increasing survival. Entinostat inhibited the immunosuppressive function of both PMN- and M-MDSC populations. Analysis of MDSC response to entinostat revealed significantly reduced arginase-1, iNOS and COX-2 levels, suggesting potential mechanisms for the altered function. We also observed significant alterations in cytokine/chemokine release in vivo with a shift towards a tumor suppressive microenvironment.</p> <p>Conclusions: Our results demonstrate that entinostat enhances the antitumor effect of PD-1 targeting through functional inhibition of MDSCs, and a transition away from an immune suppressive tumor microenvironment. These data provide a mechanistic rationale for the clinical testing and potential markers of response of this novel combination in solid tumor patients.

http://ift.tt/2ugggob

Sorafenib in patients with hepatocellular carcinoma - results of the observational INSIGHT study

Purpose: Sorafenib is the only currently approved systemic therapy for advanced hepatocellular carcinoma (HCC). We aimed to evaluate the safety and efficacy of sorafenib therapy in patients with HCC under real-life conditions regarding patient, tumor characteristics and any adverse events at study entry and at follow-up visits every 2-4 months. <br /><br />Experimental Design: The present INSIGHT study is a non-interventional, prospective, multicenter, observational study performed in 124 sites across Austria and Germany between 2008 and 2014.<br /><br />Results: Median overall survival and time to progression (RECIST) were found to be dependent on baseline Barcelona Clinic Liver Cancer (BCLC) tumor stage (A: 29.2, B: 19.6, C: 13.6, D: 3.1 and A: 6.0, B: 5.5, C: 3.9, and D: 1.7 months respectively), Child-Pugh liver function (A: 17.6, B: 8.1, C: 5.6 and A: 5.3, B: 3.3, C: 2.5 months, respectively), and performance status of the patient; however, age did not affect prognosis. Sorafenib-related adverse events at any grade occurred in 64.9% of patients, with diarrhea (35.4%), hand-foot-skin reaction (HFSR) (16.6%), nausea (10.3%), and fatigue (11.2%) occurring most frequently. <br /><br />Conclusions: Sorafenib treatment was shown to be effective in a real-life setting, in agreement with previously reported clinical trial data. The therapy was found to have an acceptable safety profile, with predominantly mild to moderate side effects.

http://ift.tt/2uPpg0L

Targeting AXL and mTOR pathway overcomes primary and acquired resistance to WEE1 inhibition in small cell lung cancer

Purpose: Drugs targeting DNA repair and cell cycle checkpoints have emerged as promising therapies for small cell lung cancer (SCLC). Among these, the WEE1 inhibitor AZD1775 has shown clinical activity in a subset of SCLC patients, but resistance is common. Understanding primary and acquired resistance mechanisms will be critical for developing effective WEE1 inhibitor combinations. <p>Experimental Design: AZD1775 sensitivity in SCLC cell lines was correlated with baseline expression level of 200 total or phosphorylated proteins measured by reverse phase protein array (RPPA) to identify predictive markers of primary resistance. We further established AZD1775 acquired-resistant models to identify mechanism of acquired resistance. Combination regimens were tested to overcome primary and acquired resistance to AZD1775 in in vitro and in vivo SCLC models.</p> <p>Results: High-throughput proteomic profiling demonstrate that SCLC models with primary resistance to AZD1775 express high levels of AXL and phosphorylated S6 and that WEE1/AXL or WEE1/mTOR inhibitor combinations overcome resistance in vitro and in vivo. Furthermore, AXL, independently and via mTOR, activates the ERK pathway, leading to recruitment and activation of another G2-checkpoint protein, CHK1. AZD1775 acquired-resistant models demonstrated upregulation of AXL, pS6, and MET, and resistance was overcome with the addition of AXL (TP0903), dual-AXL/MET (cabozantinib), or mTOR (RAD001) inhibitors.</p> <p>Conclusions: AXL promotes resistance to WEE1 inhibition via downstream mTOR signaling and resulting activation of a parallel DNA damage repair pathway, CHK1. These findings suggest rational combinations to enhance the clinical efficacy of AZD1775, which is currently in clinical trials for SCLC and other malignancies.

http://ift.tt/2ugESNF

Spread of resistant gram negatives in a Sri Lankan intensive care unit

Infections with multi drug resistant (MDR) organisms are a major problem in intensive care units (ICUs). Proper infection control procedures are mandatory to combat the spread of resistant organisms within ICU...

http://ift.tt/2vaWbvQ

Reduced Protein Expression in a Virus Attenuated by Codon Deoptimization

A general means of viral attenuation involves the extensive recoding of synonymous codons in the viral genome. The mechanistic underpinnings of this approach remain unclear, however. Using quantitative proteomics and RNA sequencing, we explore the molecular basis of attenuation in a strain of bacteriophage T7 whose major capsid gene was engineered to carry 182 suboptimal codons. We do not detect transcriptional effects from recoding. Proteomic observations reveal that translation is halved for the recoded major capsid gene, and a more modest reduction applies to several co-expressed downstream genes. We observe no changes in protein abundances of other co-expressed genes that are encoded upstream. Viral burst size, like capsid protein abundance, is also decreased by half. Together, these observations suggest that, in this virus, reduced translation of an essential polycistronic transcript and diminished virion assembly form the molecular basis of attenuation.

http://ift.tt/2ubtyBt

Genome-Wide Sequence and Expression Analysis of the NAC Transcription Factor Family in Polyploid Wheat

Many important genes in agriculture correspond to transcription factors which regulate a wide range of pathways from flowering to responses to disease and abiotic stresses. In this study, we identified 5,776 transcription factors in hexaploid wheat (Triticum aestivum) and classified them into gene families. We further investigated the NAC family exploring the phylogeny, C-terminal domain conservation and expression profiles across 308 RNA-seq samples. Phylogenetic trees of NAC domains indicated that wheat NACs divided into eight groups similar to rice (Oryza sativa) and barley (Hordeum vulgare). C-terminal domain motifs were frequently conserved between wheat, rice and barley within phylogenetic groups, however this conservation was not maintained across phylogenetic groups. Three homoeologous copies were present for 58% of NACs, whereas evidence of single homoeolog gene loss was found for 33% of NACs. We explored gene expression patterns across a wide range of developmental stages, tissues, and abiotic stresses. We found that more phylogenetically related NACs shared more similar expression patterns compared to more distant NACs. However, within each phylogenetic group there were clades with diverse expression profiles. We carried out a co-expression analysis on all wheat genes and identified 37 modules of co-expressed genes of which 23 contained NACs. Using GO term enrichment we obtained putative functions for NACs within co-expressed modules including responses to heat and abiotic stress and responses to water: these NACs may represent targets for breeding or biotechnological applications. This study provides a framework and data for hypothesis generation for future studies on NAC transcription factors in wheat.

http://ift.tt/2vaNXno

Evaluation of serum microRNA biomarkers for gastric cancer based on blood and tissue pools profiling: the importance of miR-21 and miR-331

Evaluation of serum microRNA biomarkers for gastric cancer based on blood and tissue pools profiling: the importance of miR-21 and miR-331

British Journal of Cancer 117, 266 (11 July 2017). doi:10.1038/bjc.2017.190

Authors: Marek Sierzega, Marcin Kaczor, Piotr Kolodziejczyk, Jan Kulig, Marek Sanak & Piotr Richter

http://ift.tt/2tA4zVK

Sequential versus concurrent chemotherapy for adjuvant breast cancer: does dose intensity matter?

Sequential versus concurrent chemotherapy for adjuvant breast cancer: does dose intensity matter?

British Journal of Cancer 117, 157 (11 July 2017). doi:10.1038/bjc.2017.176

Authors: N LeVasseur & S K Chia

http://ift.tt/2tzPoMc

Akt as a target for cancer therapy: more is not always better (lessons from studies in mice)

Akt as a target for cancer therapy: more is not always better (lessons from studies in mice)

British Journal of Cancer 117, 159 (11 July 2017). doi:10.1038/bjc.2017.153

Authors: Qi Wang, Xinyu Chen & Nissim Hay

http://ift.tt/2sbffcE

Comment on ‘Renewed interest in the progesterone receptor in breast cancer’

Comment on 'Renewed interest in the progesterone receptor in breast cancer'

British Journal of Cancer 117, e1 (11 July 2017). doi:10.1038/bjc.2017.90

Authors: Giovanni Simone, Sergio Diotaiuti, Maria Digennaro, Domenico Sambiasi, Simona De Summa, Stefania Tommasi, Rosanna Altieri, Annita Mangia, Caterina Dantona & Angelo Paradiso

http://ift.tt/2o2t9e9

Sequential vs concurrent epirubicin and docetaxel as adjuvant chemotherapy for high-risk, node-negative, early breast cancer: an interim analysis of a randomised phase III study from the Hellenic Oncology Research Group

Sequential vs concurrent epirubicin and docetaxel as adjuvant chemotherapy for high-risk, node-negative, early breast cancer: an interim analysis of a randomised phase III study from the Hellenic Oncology Research Group

British Journal of Cancer 117, 164 (11 July 2017). doi:10.1038/bjc.2017.158

Authors: Dimitrios Mavroudis, Emmanouil Saloustros, Ioannis Boukovinas, Pavlos Papakotoulas, Stylianos Kakolyris, Nikolaos Ziras, Charalampos Christophylakis, Nikolaos Kentepozidis, Georgios Fountzilas, Georgios Rigas, Ioannis Varthalitis, Konstantinos Kalbakis, Sofia Agelaki, Dora Hatzidaki & Vasilios Georgoulias

http://ift.tt/2t0HU7U

KIF15 promotes pancreatic cancer proliferation via the MEK–ERK signalling pathway

KIF15 promotes pancreatic cancer proliferation via the MEK–ERK signalling pathway

British Journal of Cancer 117, 245 (11 July 2017). doi:10.1038/bjc.2017.165

Authors: Jie Wang, Xingjun Guo, Chencheng Xie & Jianxin Jiang

http://ift.tt/2rRDVHA

Predicting Infectious ComplicatioNs in Children with Cancer: an external validation study

Predicting Infectious ComplicatioNs in Children with Cancer: an external validation study

British Journal of Cancer 117, 171 (11 July 2017). doi:10.1038/bjc.2017.154

Authors: Gabrielle M Haeusler, Karin A Thursky, Francoise Mechinaud, Franz E Babl, Richard De Abreu Lourenco, Monica A Slavin & Robert Phillips

http://ift.tt/2ro8N5u

Impact of body mass index on ovarian cancer survival varies by stage

Impact of body mass index on ovarian cancer survival varies by stage

British Journal of Cancer 117, 282 (11 July 2017). doi:10.1038/bjc.2017.162

Authors: Elisa V Bandera, Valerie S Lee, Bo Qin, Lorna Rodriguez-Rodriguez, C Bethan Powell & Lawrence H Kushi

http://ift.tt/2s1FZzp

The influence of timing of radiation therapy following breast-conserving surgery on 10-year disease-free survival

The influence of timing of radiation therapy following breast-conserving surgery on 10-year disease-free survival

British Journal of Cancer 117, 179 (11 July 2017). doi:10.1038/bjc.2017.159

Authors: Marissa C van Maaren, Reini W Bretveld, Jan J Jobsen, Renske K Veenstra, Catharina GM Groothuis-Oudshoorn, Hendrik Struikmans, John H Maduro, Luc JA Strobbe, Philip MP Poortmans & Sabine Siesling

http://ift.tt/2s1W206

Comment on 'The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis'

Comment on 'The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis'

British Journal of Cancer 117, e3 (11 July 2017). doi:10.1038/bjc.2017.184

Author: Alain Braillon

http://ift.tt/2tzFtX0

Phase 2 study of combination SPI-1620 with docetaxel as second-line advanced biliary tract cancer treatment

Phase 2 study of combination SPI-1620 with docetaxel as second-line advanced biliary tract cancer treatment

British Journal of Cancer 117, 189 (11 July 2017). doi:10.1038/bjc.2017.160

Authors: Richard Kim, E Gabriela Chiorean, Manik Amin, Caio Max S Rocha-Lima, Jitendra Gandhi, William P Harris, Tao Song & David Portnoy

http://ift.tt/2tqpLxz

MicroRNA-199b-5p attenuates TGF-β1-induced epithelial–mesenchymal transition in hepatocellular carcinoma

MicroRNA-199b-5p attenuates TGF-β1-induced epithelial–mesenchymal transition in hepatocellular carcinoma

British Journal of Cancer 117, 233 (11 July 2017). doi:10.1038/bjc.2017.164

Authors: Shao-jun Zhou, Fu-yao Liu, An-hong Zhang, Hui-fang Liang, Ye Wang, Rong Ma, Yuan-hui Jiang & Nian-feng Sun

http://ift.tt/2s1B1mC

Pharmacologically directed strategies in academic anticancer drug discovery based on the European NCI compounds initiative

Pharmacologically directed strategies in academic anticancer drug discovery based on the European NCI compounds initiative

British Journal of Cancer 117, 195 (11 July 2017). doi:10.1038/bjc.2017.167

Authors: Hans R Hendriks, Anne-Sophie Govaerts, Iduna Fichtner, Sally Burtles, Andrew D Westwell & Godefridus J Peters

http://ift.tt/2s83Nz5

Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia

Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia

British Journal of Cancer 117, 256 (11 July 2017). doi:10.1038/bjc.2017.152

Authors: Maribel Forero-Castro, Cristina Robledo, Rocío Benito, Irene Bodega-Mayor, Inmaculada Rapado, María Hernández-Sánchez, María Abáigar, Jesús Maria Hernández-Sánchez, Miguel Quijada-Álamo, José María Sánchez-Pina, Mónica Sala-Valdés, Fernanda Araujo-Silva, Alexander Kohlmann, José Luis Fuster, Maryam Arefi, Natalia de las Heras, Susana Riesco, Juan N Rodríguez, Lourdes Hermosín, Jordi Ribera, Mireia Camos Guijosa, Manuel Ramírez, Cristina Díaz de Heredia Rubio, Eva Barragán, Joaquín Martínez, José M Ribera, Elena Fernández-Ruiz & Jesús-María Hernández-Rivas

http://ift.tt/2rBQr0B

Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies

Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies

British Journal of Cancer 117, 203 (11 July 2017). doi:10.1038/bjc.2017.168

Authors: Muhammad A Alvi, Maurice B Loughrey, Philip Dunne, Stephen McQuaid, Richard Turkington, Marc-Aurel Fuchs, Claire McGready, Victoria Bingham, Brendan Pang, Wendy Moore, Perry Maxwell, Mark Lawler, Jacqueline A James, Graeme I Murray, Richard H Wilson & Manuel Salto-Tellez

http://ift.tt/2rRRneC

Prioritising action on occupational carcinogens in Europe: a socioeconomic and health impact assessment

Prioritising action on occupational carcinogens in Europe: a socioeconomic and health impact assessment

British Journal of Cancer 117, 274 (11 July 2017). doi:10.1038/bjc.2017.161

Authors: J W Cherrie, S Hutchings, M Gorman Ng, R Mistry, C Corden, J Lamb, A Sánchez Jiménez, A Shafrir, M Sobey, M van Tongeren & L Rushton

http://ift.tt/2s86EYA

Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy

Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy

British Journal of Cancer 117, 210 (11 July 2017). doi:10.1038/bjc.2017.175

Authors: K J Gash, A C Chambers, D E Cotton, A C Williams & M G Thomas

http://ift.tt/2tzQKqh

Radiation-associated breast cancer and gonadal hormone exposure: a report from the Childhood Cancer Survivor Study

Radiation-associated breast cancer and gonadal hormone exposure: a report from the Childhood Cancer Survivor Study

British Journal of Cancer 117, 290 (11 July 2017). doi:10.1038/bjc.2017.169

Authors: Chaya S Moskowitz, Joanne F Chou, Charles A Sklar, Dana Barnea, Cécile M Ronckers, Danielle Novetsky Friedman, Joseph P Neglia, Lucie Turcotte, Rebecca M Howell, Tara O Henderson, Gregory T Armstrong, Wendy M Leisenring, Leslie L Robison, Flora E van Leeuwen, Malcolm C Pike & Kevin C Oeffinger

http://ift.tt/2tqss25

Prevalence of somatic mitochondrial mutations and spatial distribution of mitochondria in non-small cell lung cancer

Prevalence of somatic mitochondrial mutations and spatial distribution of mitochondria in non-small cell lung cancer

British Journal of Cancer 117, 220 (11 July 2017). doi:10.1038/bjc.2017.155

Authors: Daniel Kazdal, Alexander Harms, Volker Endris, Roland Penzel, Mark Kriegsmann, Florian Eichhorn, Thomas Muley, Albrecht Stenzinger, Nicole Pfarr, Wilko Weichert & Arne Warth

http://ift.tt/2rBL6q1

Comment on ‘Effect of population breast screening on breast cancer mortality up to 2005 in England and Wales: an individual-level cohort study’

Comment on 'Effect of population breast screening on breast cancer mortality up to 2005 in England and Wales: an individual-level cohort study'

British Journal of Cancer 117, e2 (11 July 2017). doi:10.1038/bjc.2017.101

Author: Anthony B Miller

http://ift.tt/2o2sQ2X

APOBEC3A and 3B activities render cancer cells susceptible to ATR inhibition

The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like APOBEC3A and 3B have emerged as key mutation drivers in cancer. Here we show that APOBEC3A and 3B activities impose a unique type of replication stress by inducing abasic sites at replication forks. In contrast to cells under other types of replication stress, APOBEC3A-expressing cells were selectively sensitive to ATR inhibitors (ATRi), but not to a variety of DNA replication inhibitors and DNA-damaging drugs. In proliferating cells, APOBEC3A modestly elicited ATR but not ATM. ATR inhibition in APOBEC3A-expressing cells resulted in a surge of abasic sites at replication forks, revealing an ATR-mediated negative feedback loop during replication. The surge of abasic sites upon ATR inhibition associated with increased accumulation of single-stranded DNA, a substrate of APOBEC3A, triggering an APOBEC3A-driven feedforward loop that ultimately drove cells into replication catastrophe. In a panel of cancer cell lines, ATRi selectively induced replication catastrophe in those harboring high APOBEC3A and/or 3B activities, showing that APOBEC3A and 3B activities conferred susceptibility to ATRi. Our results define an APOBEC-driven replication stress in cancer cells that may offer an opportunity for ATR-targeted therapy.

http://ift.tt/2tGoLat

Potential of Terpenoids and Flavonoids from Asteraceae as Anti-Inflammatory, Antitumor, and Antiparasitic Agents

http://ift.tt/2ugvuJZ

The role of epithelial-mesenchymal transition in squamous cell carcinoma of the oral cavity

Abstract

Epithelial-mesenchymal transition (EMT) has emerged as a possible mechanism of cancer metastasizing, but strong evidence for EMT involvement in human cancer is lacking. Our aim was to compare oral spindle cell carcinoma (SpCC) as an example of EMT with oral conventional squamous cell carcinoma (SCC) with and without nodal metastases to test the hypothesis that EMT contributes to metastasizing in oral SCC. Thirty cases of oral SCC with and without nodal metastasis and 15 cases of SpCC were included. Epithelial (cytokeratin, E-cadherin), mesenchymal (vimentin, N-cadherin), and stem cell markers (ALDH-1, CD44, Nanog, Sox-2) and transcription repressors (Snail, Slug, Twist) were analyzed immunohistochemically. We also analyzed the expression of microRNAs miR-141, miR-200 family, miR-205, and miR-429. SpCC exhibited loss of epithelial markers and expression of mesenchymal markers or coexpression of both up-regulation of transcription repressors and down-regulation of the investigated microRNAs. SCC showed only occasional focal expression of mesenchymal markers at the invasive front. No other differences were observed between SCC with and without nodal metastases except for a higher expression of ALDH-1 in SCC with metastases. Our results suggest that SpCC is an example of true EMT but do not support the hypothesis that EMT is involved in metastasizing of conventional SCC. Regarding oral SCC progression and metastasizing, we have been facing a shift from the initial enthusiasm for the EMT concept towards a more critical approach with "EMT-like" and "partial EMT" concepts. The real question, though, is, is there no EMT at all?

http://ift.tt/2uPeTd6

Comparison of the Clinical Characteristics of Pneumocystis Pneumonia between Patients with Rheumatoid Arthritis Being Treated with Biologics and Those Being Treated without Biologics

Objective. The aim of this study was to compare the clinical characteristics of pneumocystis pneumonia (PCP) between patients with rheumatoid arthritis (RA) being treated with biologics and those being treated without biologics. Methods. From 8,630 patients with RA in our institution, we enrolled 24 patients who had developed PCP during the course of their treatment. They were divided into two groups according to the treatment they were receiving for RA: the biologics group () and the nonbiologics group (). Clinical characteristics of PCP were compared between the two groups. Results. At PCP diagnosis, the biologics group showed significantly lower serum levels of β-D-glucan and C-reactive protein than the nonbiologics group, while the biologics group had significantly higher lymphocyte counts than the nonbiologics group. In the nonbiologics group, lower lymphocyte counts were associated with higher β-D-glucan levels; however, this was not observed in the biologics group. Conclusion. The finding that RA patients being treated with biologics developed PCP with relatively normal lymphocyte counts and lower β-D-glucan levels suggests that the pathophysiology of PCP in those patients is different from that in patients being treated with other antirheumatic drugs.

http://ift.tt/2uP98vR

Detection of Folliculin Gene Mutations in Two Chinese Families with Birt-Hogg-Dube Syndrome

Birt-Hogg-Dube syndrome (BHD, OMIM#135150) is a rare disease in clinic; it is characterized by skin fibrofolliculomas, pulmonary cysts with an increased risk of recurrent pneumothorax, renal cysts, and renal neoplasms. Previous studies have demonstrated that variants in folliculin (FLCN, NM_144997) are mainly responsible for this disease. In this research, we enrolled two BHD families and applied direct sequencing of FLCN to explore the genetic lesions in them. Two FLCN mutations were identified: one is a novel deletion variant (c.668delA/p.N223TfsX19), while the other is a previously reported insertion mutation (c.1579_1580insA/p.R527QfsX75). And the pathogenicity of both variants was confirmed by cosegregation assay. Bioinformatics analysis showed that c.668delA may lead to functional haploinsufficiency of FLCN because mRNA carrying this mutation exhibits a faster degradation rate comparing to the wild type. Real-time qPCR also confirmed that the mRNA level of FLCN expression in the proband was decreased significantly compared with the controls, which may disrupt the mTOR pathway and lead to BHD. The insertion mutation (c.1579_1580insA) was predicted to cause a prolonged amino acid sequence of FLCN. The present identification of two mutations not only further supports the important role of tumor suppressor FLCN in BHD and primary spontaneous pneumothorax, but also expands the spectrum of FLCN mutations and will provide insight into genetic diagnosis and counseling of families with BHD.

http://ift.tt/2uOEZNt

Current Nucleic Acid Extraction Methods and Their Implications to Point-of-Care Diagnostics

Nucleic acid extraction (NAE) plays a vital role in molecular biology as the primary step for many downstream applications. Many modifications have been introduced to the original 1869 method. Modern processes are categorized into chemical or mechanical, each with peculiarities that influence their use, especially in point-of-care diagnostics (POC-Dx). POC-Dx is a new approach aiming to replace sophisticated analytical machinery with microanalytical systems, able to be used near the patient, at the point of care or point of need. Although notable efforts have been made, a simple and effective extraction method is still a major challenge for widespread use of POC-Dx. In this review, we dissected the working principle of each of the most common NAE methods, overviewing their advantages and disadvantages, as well their potential for integration in POC-Dx systems. At present, it seems difficult, if not impossible, to establish a procedure which can be universally applied to POC-Dx. We also discuss the effects of the NAE chemicals upon the main plastic polymers used to mass produce POC-Dx systems. We end our review discussing the limitations and challenges that should guide the quest for an efficient extraction method that can be integrated in a POC-Dx system.

http://ift.tt/2uOzvlD

EM Nerd-The Case of the Tarnished Standard

Anyone who has spent some time in a cardiac intensive care unit understands the physiologic appeal of the intra-aortic balloon pump (IABP). Anecdotally its use improves multiple clinical endpoints that for years have been considered surrogates for patient important outcomes. And yet, despite these physiologic advantages when examined in a rigorous fashion, IABPs have failed […]

EMCrit by Rory Spiegel.

http://ift.tt/2ufQXmb

Evaluation of serum microRNA biomarkers for gastric cancer based on blood and tissue pools profiling: the importance of miR-21 and miR-331

http://ift.tt/2tccO98

Sequential versus concurrent chemotherapy for adjuvant breast cancer: does dose intensity matter?

http://ift.tt/2tFWsJt

Comment on ‘Renewed interest in the progesterone receptor in breast cancer’

http://ift.tt/2tFTWCJ

Sequential vs concurrent epirubicin and docetaxel as adjuvant chemotherapy for high-risk, node-negative, early breast cancer: an interim analysis of a randomised phase III study from the Hellenic Oncology Research Group

http://ift.tt/2tbOvrQ

KIF15 promotes pancreatic cancer proliferation via the MEK–ERK signalling pathway

http://ift.tt/2tG5lTp

The influence of timing of radiation therapy following breast-conserving surgery on 10-year disease-free survival

http://ift.tt/2tbP70x

Comment on 'The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis'

http://ift.tt/2tG5lCT

Phase 2 study of combination SPI-1620 with docetaxel as second-line advanced biliary tract cancer treatment

http://ift.tt/2tbBHSr

MicroRNA-199b-5p attenuates TGF-β1-induced epithelial–mesenchymal transition in hepatocellular carcinoma

http://ift.tt/2tGb1wk

Pharmacologically directed strategies in academic anticancer drug discovery based on the European NCI compounds initiative

http://ift.tt/2tc93AA

Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies

http://ift.tt/2tbDK96

Prioritising action on occupational carcinogens in Europe: a socioeconomic and health impact assessment

http://ift.tt/2tcaD5v

Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy

http://ift.tt/2tGgqUw

Radiation-associated breast cancer and gonadal hormone exposure: a report from the Childhood Cancer Survivor Study

http://ift.tt/2t1EKBj

Prevalence of somatic mitochondrial mutations and spatial distribution of mitochondria in non-small cell lung cancer

http://ift.tt/2tKRyt5

Comment on ‘Effect of population breast screening on breast cancer mortality up to 2005 in England and Wales: an individual-level cohort study’

http://ift.tt/2t1Vfxj

Efficacy and safety of electroacupuncture in acute decompensated heart failure: a study protocol for a randomized, patient- and assessor-blinded, sham controlled trial

The purpose of this trial is to evaluate the effectiveness and safety of electroacupuncture in the treatment of acute decompensated heart failure compared with sham electroacupuncture.

http://ift.tt/2tKnZb4

Aphrodisiac potentials of the ethanol extract of Aloe barbadensis Mill. root in male Wistar rats

Aloe barbadensis (AB) is a short stemmed succulent medicinal herb that is being used by locals in Nigeria to enhance libido. Therefore this study evaluates the aphrodisiac potential an...

http://ift.tt/2t1kyjd

Platelet releasate promotes breast cancer growth and angiogenesis via VEGF–integrin cooperative signalling

http://ift.tt/2u622G6

Modulating cancer cell survival by targeting intracellular cholesterol transport

http://ift.tt/2sMKYks

UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins–TGF-β1–FAP-α

http://ift.tt/2u5PtdA

The TGF-β signalling negative regulator PICK1 represses prostate cancer metastasis to bone

http://ift.tt/2sNrbkE

HMGA1 expression levels are elevated in pancreatic intraepithelial neoplasia cells in the Ptf1a-Cre; LSL-KrasG12D transgenic mouse model of pancreatic cancer

http://ift.tt/2u5PcaE

Spinal Cord Neurons Isolation and Culture from Neonatal Mice

This study presents a technique for the isolation of neurons from WT neonatal mice. It requires the careful dissection of the spinal cord from the neonatal mouse, followed by the separation of neurons from the spinal cord tissue through mechanical and enzymatic cleavage.

http://ift.tt/2sNfvhU

Periaortitis induced by epirubicin and cyclophosphamide for a patient with advanced breast cancer

Abstract

Aortitis is an extremely rare condition, and it may mimic febrile neutropenia during cancer chemotherapy. A 55-year-old female diagnosed with T2N1M1 stage IV breast carcinoma received chemotherapy with EC (epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² every 3 weeks). At the eleventh day after the first administration of EC, she developed a high-grade fever of 38 °C and stomatitis. We started the intravenous administration of antibiotics at hospitalization, because the laboratory data showed normal white blood cell values 3800/μl but a severe inflammatory reaction (CRP 25.13 mg/dl). The fever and high CRP value continued, and the WBC rose to 14,500/μl at 20th day. However, her condition was stable. On the 25th day after the administration of EC, she complained of back pain, so we performed computed tomography (CT) again and observed thickening of the rind surrounding the descending aorta and bilateral pleural effusion, indicating acute periaortitis. We performed examinations concerning vasculitis and connective tissue disease, but the values were all within normal ranges showing no relationship with other diseases. We stopped the administration of antibiotics on the 20th day, and while we did not administer corticosteroids, however, the fever was resolved and her WBC decreased. She was discharged on day 33, and the other chemotherapy was restarted with pertuzumab, trastuzumab and docetaxel. The patient has remained well without inflammatory reactions. CT at 90 days after EC therapy showed the resolution of the thickened rind of the descending aorta and no aneurysmic changes.

http://ift.tt/2tFmw7D

A Graphical User Interface for Software-assisted Tracking of Protein Concentration in Dynamic Cellular Protrusions

We present a software solution for semi-automated tracking of relative protein concentration along the length of dynamic cellular protrusions.

http://ift.tt/2uaBNOa

Effectiveness of arthroscopically assisted surgery for ankle fractures: a meta-analysis

Publication date: Available online 11 July 2017
Source:Injury
Author(s): Kyoung Min Lee, Sonya Ahmed, Moon Seok Park, Ki Hyuk Sung, Seung Yeol Lee, Seungbum Koo
IntroductionThis meta-analysis was performed to determine whether the arthroscopically assisted open reduction and internal fixation (ORIF) for ankle fractures is more beneficial than the conventional ORIF.MethodsArticles in electronic medial databases were searched between March 1983 and August 2016, including Pubmed and SCOPUS. We included the studies with comparative design comparing the surgical outcomes between the arthroscopically assisted ORIF for ankle fractures and the conventional ORIF. Finally, two RCTs and two retrospective comparative studies were included for analysis. Mean and standard deviation (SD) of postoperative functional scores, number of subjects, and P-values were extracted from the studies. In addition, postoperative follow-up period, fracture type, and study quality were collected.ResultsThe pooled effect size of the four studies 0.535 (95% CI, 0.247–0.823) in Hedges's g, which favored the arthroscopically assisted ORIF over conventional ORIF. There was no evidence of publication bias in funnel plot and in Egger's test (p=0.534).ConclusionThe arthroscopically assisted ORIF for ankle fractures were more beneficial than the conventional ORIF in the current evidences. However, since it needs more medical cost and longer operation time, possible additional complications and cost effectiveness are to be validated in future studies.



http://ift.tt/2sMoH6k

A Representative Assessment of the Management of Open Fractures of the Lower Limb within UK Orthoplastic Centres: A Two-Centre Audit of Compliance with National Standards.

Publication date: Available online 11 July 2017
Source:Injury
Author(s): B. Rymer, E.O.F. Dimovska, D.T.S. Chou, R. Choa, B. Davis, S. Huq
BackgroundOpen fractures of the lower limb represent a complex and varied array of injuries. The BOAST 4 document produced by BAPRAS and the BOA provides standards on how to manage these patients, and NICE have recently produced additional guidance. We aimed to assess concordance with these standards in a large cohort representative of UK orthoplastic centres.MethodsPatients admitted to the orthoplastic units at Norfolk and Norwich University Hospital and Royal Stoke University Hospital with open lower limb fractures between 2009 and 2014 were included. Data was gathered from notes and endpoints based on the BOAST 4 document.ResultsIn total, 84 patients were included across the two sites, with 83 having their initial debridement within 24hours (98.8%). Forty-two patients had a documented out-of-hours initial surgery. Of these, 10 (23.8%) had an indication for urgent surgery. This pattern was consistent across both hospitals. A plastic surgeon was present at 33.3% of initial operations. Of 78 patients receiving definitive soft tissue cover, 56.4% had cover within 72hours and 78.2% within 7 days. Main reasons for missing these targets were transfer from other hospitals, plastic surgeons not present at initial operation and intervening critical illness.ConclusionsThis study has identified key areas for improving compliance with the national BOAST 4 and NICE standards. Out-of-hours operating is occurring unnecessarily and time targets are being missed. The development of dedicated referral pathways and a true orthoplastic approach are required to improve the management of this complex set of injuries.



http://ift.tt/2u5thQM

Implications of three-dimensional modeling of the proximal femur for cephalomedullary nailing: An Asian cadaver study

Publication date: Available online 11 July 2017
Source:Injury
Author(s): Chang-Soo Chon, Bokku Kang, Han Sung Kim, Gu-Hee Jung
PurposeTo determine the variability in the ideal entry point of cephalomedullary (CM) nail around the greater trochanter (GT) and the consequent conformity with the proximal femur by analyzing three-dimensional (3D) modeling and virtual implantationMaterials and MethodsA total of 105 cadaveric femurs (50 males and 55 females) underwent continuous 1.0mm slice computed tomography (CT) scans. CT images imported into Mimics^® software to reconstruct the 3D model of the proximal femur and medullary canal. PFNA-II^® was processed into a 3D model using a 3D-sensor at the actual size and optimally implanted in the proximal femur model using Mimics^® software. The ideal entry point, nail conformity with the proximal femur, and the relationship between the entry point and adjacent structures were assessed.ResultsThe ideal entry point was located a mean of 2.38mm (SD, 3.53mm) medial to the tip of GT. No lateral cortex impingement of the proximal femur occurred in the coronal plane based on the recommended point. However, a disparity in the sagittal plane between the proximal shaft and nail curvature was found in 47 models (44.8%). Rotation and magnification of the 3D model exposed all nails above the surface of the medial side of the GT. The proximal nail end was contained entirely within bone and circumferential endosteal cortical contact was present at the nail-bone interface.



http://ift.tt/2sMWKLC

Urinary schistosomiasis among vulnerable children in a rehabilitation home in Ibadan, Oyo state, Nigeria

Schistosomiasis is a disease of public health importance with long term complications mostly common among children, rural dwellers, poor and migrant workers. Studies have not documented the burden among migran...

http://ift.tt/2uNWPjD

Inducible clindamycin and methicillin resistant Staphylococcus aureus in a tertiary care hospital, Kathmandu, Nepal

Staphylococcus aureus, an important nosocomial pathogen, is frequently associated with infections in human. The management of the infections by it especially methicillin resistant ones...

http://ift.tt/2uNuF8d

Seroprevalence and risk factors of Toxoplasma gondii infection in pregnant women from Bobo Dioulasso, Burkina Faso

Toxoplasmosis is one of the common worldwide parasitic zoonosis due to Toxoplasma gondii (T. gondii). Toxoplasmosis during pregnancy can result in fetal and neonatal death or various congenital defects. The aim o...

http://ift.tt/2ueTkFR

Surveillance of recent HIV infections among newly diagnosed HIV cases in Germany between 2008 and 2014

The HIV surveillance system in Germany is based on mandatory, anonymous notification of newly diagnosed HIV cases by laboratories. Because the time between HIV infection and the diagnosis of HIV varies widely ...

http://ift.tt/2uNsz8D

Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis

Lymph node (LN) formation is thought to rely mainly on interactions between mesenchymal lymphoid tissue organizer cells and lymphoid tissue inducer cells. Onder et al. now show that LN formation is governed by RANK-dependent activation of lymphatic endothelial cells that control retention of lymphoid tissue inducer cells in embryonic LN anlagen.

http://ift.tt/2tamNeZ

An Ocular Commensal Protects against Corneal Infection by Driving an Interleukin-17 Response from Mucosal γδ T Cells

Although the eye is a mucosal site, there has been a long-standing controversy regarding whether a resident microbiome exists on the ocular surface. St. Leger et al. show that a microorganism that lives on the conjunctiva tunes local mucosal immunity and protects the eye from pathogenic infection.

http://ift.tt/2talCMU

Identification of Natural Regulatory T Cell Epitopes Reveals Convergence on a Dominant Autoantigen

The endogenous antigens recognized by thymus-derived Treg cells have remained largely undefined. Leonard et al. identify natural Treg cell ligands in mice, demonstrating that two recurrent Treg cell clones recognize distinct non-overlapping peptides derived from a single prostate-specific protein.

http://ift.tt/2tEZw8z

Human Secretory IgM Emerges from Plasma Cells Clonally Related to Gut Memory B Cells and Targets Highly Diverse Commensals

Magri et al. found that the human gut includes a large memory IgM+ B cell repertoire clonally related to plasma cells mounting SIgM responses against mucus-embedded commensals co-targeted by SIgA. Dually coated bacteria are detected in humans but not mice and show increased diversity and richness compared to SIgA-only-coated or uncoated bacteria.

http://ift.tt/2tEAGpf

Prevalence of multi drug resistant enteropathogenic and enteroinvasive Escherichia coli isolated from children with and without diarrhea in Northeast Indian population

Diarrheagenic Escherichia coli are associated with infantile diarrhea in the developing countries. The present study was conducted to determine the occurrence and antimicrobial resistance pattern of enteropathoge...

http://ift.tt/2tERmx8

Mike Steuerwald, MD joins The Difficult Airway Course: EMS™ as Associate Medical Director

FARMINGTON, Conn. — First Airway, LLC, the creator of The Difficult Airway Course: EMS, is pleased to announce the appointment of Mike Steuerwald, MD as the new Associate Medical Director. Dr. Steuerwald is the Director of Emergency Airway Management and the Assistant Medical Director of UW Med Flight, as well as an Assistant Professor at the University of Wisconsin School of Medicine and Public ...

http://ift.tt/2uauINA

Triple Test—a Predictor of Anastomotic Integrity in Patients Undergoing Low Anterior Resection After Neoadjuvant Chemoradiotherapy

Abstract

Anastomotic leak after low anterior resection for rectal cancer is a dreaded complication. Diversion stoma helps tiding over this crisis and it is routinely practised in most centres, especially in post chemoradiotherapy setting. But a diversion stoma has got its own problems. In this study, we attempt to use the triple test as a predictor of anastomotic integrity and thereby avoid a diverting stoma, and patients undergoing low anterior resection after neoadjuvant chemoradiotherapy were spared the trouble of a diverting stoma if the on table triple test was negative. Two hundred such consecutive patients were prospectively followed up in the postoperative period. The incidence of anastomotic leak and the factors predicting the same were analysed in this group of patients. The incidence of anastomotic leak in our study was 7%, which is much less when compared to published literature. The triple test was a reliable predictor of the integrity of anastomosis and if the test is negative, a diverting stoma can be avoided. Age more than 60 years and end-to-end anastomosis were found to be associated with increased incidence of leak, and patients with a negative triple test need not routinely undergo diversion stoma after a low anterior resection even in post chemoradiotherapy setting.

http://ift.tt/2tareGX

Reply to letter to the editor of Gut

Dear editor,

A systematic review of studies mostly evaluating the role of fully covered self-expandable metal stents (FCSEMS) for drainage of pancreatic fluid collections (PFCs) reported a pooled adverse event rate of 23%.1 To overcome the limitations of FCSEMS and to minimise adverse events, a lumen-apposing metal stent (LAMS) was recently developed. The new stent is a single-step drainage device that is very different in design and mechanics from FCSEMS and hence warranted a change in the terminology, so that it is now referred to as LAMS (not a novel FCSEMS). The authors state that their observations2 are in variance with the high adverse event rate reported in our ongoing randomised trial3 and have cited retrospective or prospective registry data from other investigators. In one of the studies cited by the authors, major complications were encountered in 9% and minor complications in 25%...

http://ift.tt/2u54Tiw

Prevalence of serrated polyposis syndrome in an FIT-based colorectal cancer screening cohort in Italy

To the Editor

We read with interest the recent data reported by IJspeert et al,1 Biswas et al2 and Moreira et al3 whom evaluated the prevalence of serrated polyposis syndrome (SPS), a disease characterised by the development of multiple serrated polyps throughout the colon with an increased risk to develop colorectal cancer (CRC),4 inside CRC screening programmes. A guaiac faecal occult blood test cohort from the UK showed a frequency of SPS ranging from 0.03% to 0.66%.12 Other cohorts based on primary colonoscopy showed a prevalence of SPS between 0.1% and 0.4%.1 The only published data on SPS frequency within faecal immunochemical test (FIT) programmes are from Spain and ranged from 0.34% to 0.8%.13 Since FIT has widely become the method of choice for CRC screening, data from other...

http://ift.tt/2sMti8n

An unusual cause of colonic stricture with polyps

Clinical presentation

A 70-year-old man with no history of IBD was admitted to our department with right-sided abdominal pain and bloating. He was a non-smoker and a non-alcoholic drinker. Vital signs on initial examination were within normal range. Abdominal examination revealed a palpable tender mass (5x5 cm) in the right abdomen. Laboratory results were as follows: white cell count, 13.4x10⁹/L; haemoglobin, 13.5 g/dL; platelet count, 311x10⁹/L; erythrocyte sedimentation rate, 64 mm/hour; albumin, 3.62 g/dL; and C-reactive protein, 3.97 mg/dL.

Abdominal CT revealed a thickening of the wall (localised high-density mass-forming lesion) in the ascending colon (figure 1A). Colonoscopy revealed a large polyposis with finger-like projections in the ascending colon (figure 1B). The endoscope could not be inserted beyond this point; however, lower GI radiography revealed a colonic stricture and polypoid lesions (figure 1C). Infectious enteritis and intestinal tuberculosis were excluded based on negative bacterial and tuberculosis cultures...

http://ift.tt/2u5td3x

Reply to letter to the editor of Gut

Dear editor,

A systematic review of studies mostly evaluating the role of fully covered self-expandable metal stents (FCSEMS) for drainage of pancreatic fluid collections (PFCs) reported a pooled adverse event rate of 23%.1 To overcome the limitations of FCSEMS and to minimise adverse events, a lumen-apposing metal stent (LAMS) was recently developed. The new stent is a single-step drainage device that is very different in design and mechanics from FCSEMS and hence warranted a change in the terminology, so that it is now referred to as LAMS (not a novel FCSEMS). The authors state that their observations2 are in variance with the high adverse event rate reported in our ongoing randomised trial3 and have cited retrospective or prospective registry data from other investigators. In one of the studies cited by the authors, major complications were encountered in 9% and minor complications in 25%...

http://ift.tt/2u54Tiw

Reply: 'More viral mutants, less HBsAg clearance? One size may not fit all'

We thank Dr Tseng and colleagues for their interest1 in our recent study that identified a negative association between the presence of hepatitis B virus (HBV) basal core promoter (BCP)/precore (PC) and precore (PC) variants mutants at baseline and lower likelihood of hepatitis B surface antigen (HBsAg) loss among 157 subjects with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) treated for 4 years with tenofovir therapy. 2–4 The likelihood of HBsAg loss was 41% in subjects with wild-type (WT) sequence at the BCP/PC loci versus 3% in subjects with detectable BCP/PC variants (next generation sequencing (NGS), Illumina MiSeq—threshold for detection >1%). The cohort included subjects with a broad range of HBV genotypes (genotype A, n=36 (23%); genotype B, n=24 (15%); genotype C, n=51 (32%) and genotype D, n=46 (29%)). HBsAg loss was more common in subjects with genotype A/D (24%)...

http://ift.tt/2sMTWxS

Train-the-trainer education and colonoscopy quality indicators: where to now?

To the Editor In their recent national randomised trial published in Gut, Kaminski et al1 reported that a quality improvement intervention involving dedicated training of endoscopy centre leaders in colonoscopy provided superior improvement in adenoma detection rates (ADRs) in screening colonoscopy compared with those randomised to receive simple audit and feedback. While study results are subject to a possible Hawthorne effect given ADRs were higher during the period when study participants were aware of being monitored, the findings otherwise appeared robust with ADR improvement observed across all endoscopist specialties, colonoscopy experience and types of screening facilities. These are important findings given that ADR is a key quality indicator of colonoscopy because of its role as an independent predictor of the development interval colorectal cancer (CRC) after colonoscopy and association with CRC death.2–4

However, ADR is only one of many colonoscopy quality...

http://ift.tt/2u5q3x3

Prevalence of serrated polyposis syndrome in an FIT-based colorectal cancer screening cohort in Italy

To the Editor

We read with interest the recent data reported by IJspeert et al,1 Biswas et al2 and Moreira et al3 whom evaluated the prevalence of serrated polyposis syndrome (SPS), a disease characterised by the development of multiple serrated polyps throughout the colon with an increased risk to develop colorectal cancer (CRC),4 inside CRC screening programmes. A guaiac faecal occult blood test cohort from the UK showed a frequency of SPS ranging from 0.03% to 0.66%.12 Other cohorts based on primary colonoscopy showed a prevalence of SPS between 0.1% and 0.4%.1 The only published data on SPS frequency within faecal immunochemical test (FIT) programmes are from Spain and ranged from 0.34% to 0.8%.13 Since FIT has widely become the method of choice for CRC screening, data from other...

http://ift.tt/2sMti8n

An unusual cause of colonic stricture with polyps

Clinical presentation

A 70-year-old man with no history of IBD was admitted to our department with right-sided abdominal pain and bloating. He was a non-smoker and a non-alcoholic drinker. Vital signs on initial examination were within normal range. Abdominal examination revealed a palpable tender mass (5x5 cm) in the right abdomen. Laboratory results were as follows: white cell count, 13.4x10⁹/L; haemoglobin, 13.5 g/dL; platelet count, 311x10⁹/L; erythrocyte sedimentation rate, 64 mm/hour; albumin, 3.62 g/dL; and C-reactive protein, 3.97 mg/dL.

Abdominal CT revealed a thickening of the wall (localised high-density mass-forming lesion) in the ascending colon (figure 1A). Colonoscopy revealed a large polyposis with finger-like projections in the ascending colon (figure 1B). The endoscope could not be inserted beyond this point; however, lower GI radiography revealed a colonic stricture and polypoid lesions (figure 1C). Infectious enteritis and intestinal tuberculosis were excluded based on negative bacterial and tuberculosis cultures...

http://ift.tt/2u5td3x

Targeting super-enhancer-associated oncogenes in oesophageal squamous cell carcinoma

Objectives

Oesophageal squamous cell carcinoma (OSCC) is an aggressive malignancy and the major histological subtype of oesophageal cancer. Although recent large-scale genomic analysis has improved the description of the genetic abnormalities of OSCC, few targetable genomic lesions have been identified, and no molecular therapy is available. This study aims to identify druggable candidates in this tumour.

Design

High-throughput small-molecule inhibitor screening was performed to identify potent anti-OSCC compounds. Whole-transcriptome sequencing (RNA-Seq) and chromatin immunoprecipitation sequencing (ChIP-Seq) were conducted to decipher the mechanisms of action of CDK7 inhibition in OSCC. A variety of in vitro and in vivo cellular assays were performed to determine the effects of candidate genes on OSCC malignant phenotypes.

Results

The unbiased high-throughput small-molecule inhibitor screening led us to discover a highly potent anti-OSCC compound, THZ1, a specific CDK7 inhibitor. RNA-Seq revealed that low-dose THZ1 treatment caused selective inhibition of a number of oncogenic transcripts. Notably, further characterisation of the genomic features of these THZ1-sensitive transcripts demonstrated that they were frequently associated with super-enhancer (SE). Moreover, SE analysis alone uncovered many OSCC lineage-specific master regulators. Finally, integrative analysis of both THZ1-sensitive and SE-associated transcripts identified a number of novel OSCC oncogenes, including PAK4, RUNX1, DNAJB1, SREBF2 and YAP1, with PAK4 being a potential druggable kinase.

Conclusions

Our integrative approaches led to a catalogue of SE-associated master regulators and oncogenic transcripts, which may significantly promote both the understanding of OSCC biology and the development of more innovative therapies.

http://ift.tt/2sMuJ74

The low FODMAP diet: recent advances in understanding its mechanisms and efficacy in IBS

There is an intensifying interest in the interaction between diet and the functional GI symptoms experienced in IBS. Recent studies have used MRI to demonstrate that short-chain fermentable carbohydrates increase small intestinal water volume and colonic gas production that, in those with visceral hypersensitivity, induces functional GI symptoms. Dietary restriction of short-chain fermentable carbohydrates (the low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet) is now increasingly used in the clinical setting. Initial research evaluating the efficacy of the low FODMAP diet was limited by retrospective study design and lack of comparator groups, but more recently well-designed clinical trials have been published. There are currently at least 10 randomised controlled trials or randomised comparative trials showing the low FODMAP diet leads to clinical response in 50%–80% of patients with IBS, in particular with improvements in bloating, flatulence, diarrhoea and global symptoms. However, in conjunction with the beneficial clinical impact, recent studies have also demonstrated that the low FODMAP diet leads to profound changes in the microbiota and metabolome, the duration and clinical relevance of which are as yet unknown. This review aims to present recent advances in the understanding of the mechanisms by which the low FODMAP diet impacts on symptoms in IBS, recent evidence for its efficacy, current findings regarding the consequences of the diet on the microbiome and recommendations for areas for future research.

http://ift.tt/2u5t687

Lymphotoxin {beta} receptor signalling executes Helicobacter pylori-driven gastric inflammation in a T4SS-dependent manner

Objective

Lymphotoxin β receptor (LTβR) signalling has been implicated in inflammation-associated tumour development in different tissues. We have analysed the role of LTβR and alternative NF-B signalling in Helicobacter pylori-mediated gastric inflammation and pathology.

Design

We analysed several ligands and receptors of the alternative NF-B pathway, RelB, p52 nuclear translocation and target genes in tissue samples of H. pylori-infected patients with different degrees of gastritis or early gastric tumours by in situ hybridisation, immunohistochemistry, Western blot and real-time PCR analyses. Molecular mechanisms involved in LTβR activation by H. pylori were assessed in vitro using human gastric cancer cell lines and distinct H. pylori isolates. The effects of blocking or agonistically activating LTβR on gastric pathology during challenge with a human pathogenic H. pylori strain were studied in a mouse model.

Results

Among the tested candidates, LT was significantly increased and activated alternative NF-B signalling was observed in the gastric mucosa of H. pylori-infected patients. H. pyloriinduced LTβR–ligand expression in a type IV secretion system-dependent but CagA-independent manner, resulting in activation of the alternative NF-B pathway, which was further enhanced by blocking canonical NF-B during infection. Blocking LTβR signalling in vivo suppressed H. pylori-driven gastritis, whereas LTβR activation in gastric epithelial cells of infected mice induced a broadened pro-inflammatory chemokine milieu, resulting in exacerbated pathology.

Conclusions

LTβR-triggered activation of alternative NF-B signalling in gastric epithelial cells executes H. pylori-induced chronic gastritis, representing a novel target to restrict gastric inflammation and pathology elicited by H. pylori, while exclusively targeting canonical NF-B may aggravate pathology by enhancing the alternative pathway.

http://ift.tt/2sMdFxW

Comparative genomics of Crohn's disease-associated adherent-invasive Escherichia coli

Objective

Adherent-invasive Escherichia coli (AIEC) are a leading candidate bacterial trigger for Crohn's disease (CD). The AIEC pathovar is defined by in vitro cell-line assays examining specific bacteria/cell interactions. No molecular marker exists for their identification. Our aim was to identify a molecular property common to the AIEC phenotype.

Design

41 B2 phylogroup E. coli strains were isolated from 36 Australian subjects: 19 patients with IBD and 17 without. Adherence/invasion assays were conducted using the I-407 epithelial cell line and survival/replication assays using the THP-1 macrophage cell line. Cytokine secretion tumour necrosis factor ((TNF)-α, interleukin (IL) 6, IL-8 and IL-10) was measured using ELISA. The genomes were assembled and annotated, and cluster analysis performed using CD-HIT. The resulting matrices were analysed to identify genes unique/more frequent in AIEC strains compared with non-AIEC strains. Base composition differences and clustered regularly interspaced palindromic repeat (CRISPR) analyses were conducted.

Results

Of all B2 phylogroup strains assessed, 79% could survive and replicate in macrophages. Among them, 11/41 strains (5 CD, 2 UCs, 5 non-IBD) also adhere to and invade epithelial cells, a phenotype assigning them to the AIEC pathovar. The AIEC strains were phylogenetically heterogeneous. We did not identify a gene (or nucleic acid base composition differences) common to all, or the majority of, AIEC. Cytokine secretion and CRISPRs were not associated with the AIEC phenotype.

Conclusions

Comparative genomic analysis of AIEC and non-AIEC strains did not identify a molecular property exclusive to the AIEC phenotype. We recommend a broader approach to the identification of the bacteria-host interactions that are important in the pathogenesis of Crohn's disease.

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