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Πέμπτη 6 Οκτωβρίου 2016

Internal versus external fixation of the anterior component in unstable fractures of the pelvic ring: pooled results from a systematic review

Abstract

Purpose

Improving reduction of the pelvic ring improves long-term functional outcomes for patients. It has been demonstrated that posterior internal fixation is necessary to adequately control fractures to the posterior ring and there is evidence that supplementing this with fixation of the anterior ring improves stability. It is accepted that internal fixation provides greater stability than external fixation of the anterior ring but long-term differences in radiographic and functional outcomes have not yet been quantified.

Methods

A search of electronic databases, reference lists and review articles from 1989 to 2015 yielded 18 studies (n = 884) that met our inclusion criteria. We included studies that discussed pelvic ring injuries in adults, reported functional or radiological outcomes or complications by anterior ring intervention and exceeded 14 patients. We excluded biomechanical and cadaver studies.

Results

Internal fixation of the anterior pelvic ring had better functional and radiographic outcomes. Residual displacement of >10 mm was less common with internal fixation (ER 0.12, 95 % CI 0.06–0.24) than external fixation (ER 0.31, 95 % CI 0.11–0.62). Unsatisfactory outcomes also occurred at a lower rate (ER 0.09, 95 % CI 0.03–0.22) compared to external fixation (ER 0.32, 95 % CI 0.18–0.50). Losses of reduction (ER 0.02, 95 % CI 0.01–0.04 versus ER 0.07, 95 % CI 0.02–0.21), malunions (ER 0.03, 95 % CI 0.01–0.08 versus ER 0.07, 95 % CI 0.02–0.21) and delayed/non-unions (ER 0.02, 95 % CI 0.01–0.05 versus ER 0.04, 95 % CI 0.02–0.07).

Conclusions

Internal fixation of the anterior pelvic ring as supplementary fixation for unstable injuries to the pelvic ring appears to result in better radiographic and functional outcomes as well as fewer complications. However, data that separated outcomes and complications in relation to interventions of the anterior pelvic ring were limited. More studies looking specifically at outcomes in relation to the type of anterior ring intervention are needed.



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A small case series of aortic balloon occlusion in trauma: lessons learned from its use in ruptured abdominal aortic aneurysms and a brief review

Abstract

Background

EndoVascular and Hybrid Trauma Management (EVTM) is an emerging concept for the early treatment of trauma patients using aortic balloon occlusion (ABO), embolization agents and stent grafts to stop ongoing traumatic bleeding. These techniques have previously been implemented successfully in the treatment of ruptured aortic aneurysm.

Aims

We describe our very recent experience of EVTM using ABO in bleeding patients and lessons learned over the last 20 years from the endovascular treatment of ruptured abdominal aortic aneurysms (rAAA). We also briefly describe current knowledge of ABO usage in trauma.

Methods

A small series of educational cases in our hospital is described, where endovascular techniques were used to gain temporary hemorrhage control. The methods used for rAAA and their applicability to EVTM with a multidisciplinary approach are presented.

Results

Establishing femoral arterial access immediately on arrival at the emergency room and use of an angiography table in the surgical suite may facilitate EVTM at an early stage. ABO may be an effective method for the temporary stabilization of severely hemodynamically unstable patients with hemorrhagic shock, and may be useful as a bridge to definitive treatment of the bleeding patients.

Conclusion

EVTM, including the usage of ABO, can be initiated on patient arrival and is feasible. Further data need to be collected to investigate proper indications for ABO, best clinical usage, results and potential complications. Accordingly, the ABOTrauma Registry has recently been set up. Existing experiences of EVTM and lessons from the endovascular treatment of rAAA may be useful in trauma management.



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How I do it. The pedicled temporoparietal fascia flap for skull base reconstruction after endonasal endoscopic approaches

Abstract

Background

Endoscopic endonasal approaches (EEA) are an alternative for removing challenging nasopharyngeal or skull base lesions. In some cases, a nasoseptal flap (NSF) is not always available and such complex procedures may lead to carotid arteries exposition and/or dura mater (DM) wide opening. Meticulous carotid coverage and DM reconstruction are crucial for preventing early and delayed complications.

Method

We propose a step-by-step description of the pedicled temporoparietal fascia flap (TPFF) technique, with a focus on its pitfalls, advantages and limits.

Conclusion

The TPFF is a reliable flap for skull base reconstruction when other pedicled flaps are not available.

Key points

1. Reliable flap even for irradiated patients

2. CT angiography with 3D reconstruction as pre-operative imaging

3. Doppler ultrasound probe to draw the artery's trajectory on skin

4. TPFF elevation concomitantly to the endoscopic procedure

5. Hemicoronal incision sufficient to harvest the TPFF

6. Superficial dissection in a plane just beneath the hair follicles

7. Dissection plane deep to the fad pad to preserve the frontal branch of the facial nerve

8. Surgical corridor wide enough to avoid any compression of the pedicle

9. Double visualization to avoid any twist and Doppler control of the STA patency

10. Close follow-up, toilet in clinics



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How cardiomyocytes sense pathophysiological stresses for cardiac remodeling

Abstract

In the past decades, the cardiovascular community has laid out the fundamental signaling cascades that become awry in the cardiomyocyte during the process of pathologic cardiac remodeling. These pathways are initiated at the cell membrane and work their way to the nucleus to mediate gene expression. Complexity is multiplied as the cardiomyocyte is subjected to cross talk with other cells as well as a barrage of extracellular stimuli and mechanical stresses. In this review, we summarize the signaling cascades that play key roles in cardiac function and then we proceed to describe emerging concepts of how the cardiomyocyte senses the mechanical and environmental stimuli to transition to the deleterious genetic program that defines pathologic cardiac remodeling. As a highlighting example of these processes, we illustrate the transition from a compensated hypertrophied myocardium to a decompensated failing myocardium, which is clinically manifested as decompensated heart failure.



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Role of CFTR in epithelial physiology

Abstract

Salt and fluid absorption and secretion are two processes that are fundamental to epithelial function and whole body fluid homeostasis, and as such are tightly regulated in epithelial tissues. The CFTR anion channel plays a major role in regulating both secretion and absorption in a diverse range of epithelial tissues, including the airways, the GI and reproductive tracts, sweat and salivary glands. It is not surprising then that defects in CFTR function are linked to disease, including life-threatening secretory diarrhoeas, such as cholera, as well as the inherited disease, cystic fibrosis (CF), one of the most common life-limiting genetic diseases in Caucasian populations. More recently, CFTR dysfunction has also been implicated in the pathogenesis of acute pancreatitis, chronic obstructive pulmonary disease (COPD), and the hyper-responsiveness in asthma, underscoring its fundamental role in whole body health and disease. CFTR regulates many mechanisms in epithelial physiology, such as maintaining epithelial surface hydration and regulating luminal pH. Indeed, recent studies have identified luminal pH as an important arbiter of epithelial barrier function and innate defence, particularly in the airways and GI tract. In this chapter, we will illustrate the different operational roles of CFTR in epithelial function by describing its characteristics in three different tissues: the airways, the pancreas, and the sweat gland.



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Preparation of thermo-responsive electrospun nanofibers containing rhodamine-based fluorescent sensor for Cu 2+ detection

Abstract

A series of Cu2+-sensing nanofibers has been successfully prepared by electrospinning of poly[(N-isopropylacrylamide)-co-(N-hydroxymethyl acrylamide)-co-(4-rhodamine hydrazonomethyl-3-hydroxy-phenyl methacrylate)] [poly(NIPAAm-co-NMA-co-RHPMA), PNNR] random copolymers. These PNNR copolymers were synthesized by free radical copolymerization of three monomers, thermo-responsive NIPAAm, chemically crosslinkable NMA and Cu2+-sensing RHPMA, with the composition of RHPMA in the range of 2.4–16.3 wt%. In acidic environments, the PNNR copolymers showed highly selective and sensitive recognition and displayed "ON-OFF" fluorescence toward Cu2+ both in solution and in solid state (thin films and nanofibers). From the quantitative analysis via Stern-Volmer plots, PNNR nanofibers exhibited comparable Stern-Volmer constants as those of PNNR solutions in the order of 104 M−1, which are much higher than those of PNNR thin films. The enhanced sensitivity of PNNR electrospun nanofibers is attributed to their higher surface area compared to dip-coating films. The PNNR nanofibers also exhibited an on/off switchable sensing behavior in response to temperature change due to the hydrophilic-hydrophobic transition of PNIPAAm. In addition, the binding of PNNR with Cu2+ is chemically reversible both in solution and in nanofibers with the treatment of Na4EDTA.



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Osteoporosis Management in Ankylosing Spondylitis

Opinion statement

Low bone mineral density (BMD) is increasingly recognized as a common comorbid condition in ankylosing spondylitis (AS). As low BMD increases fracture risk, it is important to identify and treat low BMD in patients with AS who have been shown to be at increased risk for fractures above the population normal. Since low BMD occurs early in disease, we screen during the first year of diagnosis with dual energy x-ray absorptiometry (DXA). If patients are found to have osteoporosis by T-score of less than −2.5 or if their Z-score on DXA is more than two standard deviations below the mean, we initiate therapy with bisphosphonates in males and in females who are not planning any future pregnancies. While reduction in fracture risk with bisphosphonate therapy has not been clearly defined in patients with AS, reduction in vertebral and hip fractures has been well established in primary osteoporosis and thus it is our first-line treatment. If there are contraindications to the use of bisphosphonates in the treatment of low BMD, we will consider the use of denosumab. If the patient is not receiving a TNF-alpha inhibitor (TNFi) and has active disease, we also favor early initiation of TNFi due to their positive effects on BMD though the outcome on reduction in vertebral fractures remains unclear. We counsel all patients regarding the importance of adequate intake of vitamin D and calcium per the Institute of Medicine guidelines. Patients should be encouraged to participate in weight-bearing activities with a focus on core strength and gait training.



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Understanding toxicology: mechanisms and applications



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Optimized workflow and imaging protocols for whole-body oncologic PET/MRI

Abstract

Although PET/MRI has the advantages of a simultaneous acquisition of PET and MRI, high soft-tissue contrast of the MRI images, and reduction of radiation exposure, its low profitability and long acquisition time are significant problems in clinical settings. Thus, MRI protocols that meet oncological purposes need to be used in order to reduce examination time while securing detectability. Currently, half-Fourier acquisition single-shot turbo spin echo and 3D-T1 volumetric interpolated breath-hold examination may be the most commonly used sequences for whole-body imaging due to their shorter acquisition time and higher diagnostic accuracy. Although there have been several reports that adding diffusion weighted image (DWI) to PET/MRI protocol has had no effect on tumor detection to date, in cases of liver, kidney, bladder, and prostate cancer, the use of DWI may be beneficial in detecting lesions. Another possible option is to scan each region with different MRI sequences instead of scanning the whole body using one sequence continuously. We herein report a workflow and imaging protocols for whole-body oncologic PET/MRI using an integrated system in the clinical routine, designed for the detection, for example by cancer screening, of metastatic lesions, in order to help future users optimize their workflow and imaging protocols.



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Neuroimaging findings of Zika virus infection: a review article

Abstract

Zika virus (ZIKV) is an arbovirus from the Flaviviridae family. It is usually transmitted by mosquito bite. There have been no reports of severe symptoms caused by ZIKV infection up until the last few years. In October 2013 an outbreak was reported in French Polynesia with severe neurological complications in some affected cases. In November 2015, the Ministry of Health of Brazil attributed the increased number of neonatal microcephaly cases in northeastern Brazil to congenital ZIKV infection. The rapid spread of the virus convinced the World Health Organization to announce ZIKV infection as a "Public Health Emergency of International Concern" in February 2016. The main neuroimaging findings in congenital ZIKV infection include microcephaly which is the hallmark of the disease, other malformations of cortical development (e.g., lissencephaly, heterotopia, etc.), parenchymal calcifications, unilateral or bilateral ventriculomegaly, enlarged extra-axial CSF spaces, dysgenesis of the corpus callosum, agenesis of the cavum septum pellucidum, cerebellar and brainstem hypoplasia, and ocular abnormalities. ZIKV infection may also cause Guillain-Barré syndrome and acute disseminated encephalomyelitis in adults. Familiarity with neuroimaging findings of congenital and acquired ZIKV infection is crucial to suspect this disease in residents of endemic regions and travelers to these areas.



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Calcipotriol Plus Betamethasone Dipropionate Aerosol Foam is Effective, Independent of Body Mass Index and the Extent and Severity of Psoriasis

Abstract

Introduction

Good treatment adherence is important in the effective management of psoriasis and is related to both the frequency of applications and the amount of product used versus the recommended dose. The efficacy and safety of fixed combination calcipotriol 50 µg/g (Cal) and betamethasone 0.5 mg/g as dipropionate (BD) in the treatment of psoriasis is well established; an aerosol foam formulation has been developed to enhance adherence. This subanalysis from the Phase III PSO-FAST study evaluates the amount of Cal/BD foam used during treatment and the association between the extent and severity of baseline disease.

Methods

Patients (≥18 years) with mild-to-severe body psoriasis were randomized 3:1 to once-daily Cal/BD foam or vehicle. The amount of Cal/BD foam and vehicle used over the 4-week study period was evaluated according to three baseline disease assessments: extent of body surface area (BSA) affected by psoriasis, physician's global assessment of disease severity (PGA) and modified psoriasis area and severity index (mPASI). Treatment success and mPASI75 rates were assessed according to body mass index (BMI) and body weight.

Results

323 patients were randomized to Cal/BD foam and 103 to vehicle. At week 4, the mean total amount of Cal/BD foam used was 120.8 g (n = 293), which was similar to the amount of vehicle used (128.9 g; n = 98). The total amount of Cal/BD foam used at week 4 was greater with increasing BSA and increasing severity of baseline PGA and mPASI. Throughout the study, 93.1% of patients in the Cal/BD foam group and 99.0% of patients in the vehicle group missed ≤10% of treatment applications. Treatment success and mPASI75 rates were generally similar when stratified according to BMI and body weight.

Conclusions

This subanalysis demonstrates that Cal/BD aerosol foam is used appropriately and is effective for the treatment of psoriasis, independent of BMI and the extent or severity of disease.

Clinical trials number

NCT01866163.

Funding

LEO Pharma A/S.



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Macrobrachium rosenbergii nodavirus infection in a giant freshwater prawn hatchery in Indonesia

A pathogen of giant freshwater prawn, Macrobrachium rosenbergii, was recently recorded in a hatchery in Yogyakarta. The clinical symptom in post-larvae (PL) was a whitish appearance of the muscles in the tail. H...

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Combined spinal–epidural anesthesia for radical hysterectomy in a patient with Sjȍgren syndrome with progressive interstitial lung disease

Interstitial lung disease (ILD), which is the most common form of respiratory involvement of Sjȍgren syndrome (SS), is highly associated with postoperative pulmonary complications after surgery. We report the ...

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Meta-analysis of randomized clinical trials comparing fistulectomy versus fistulotomy for low anal fistula

We evaluated the efficacy of fistulectomy compared to fistulotomy, and which procedure was the best procedure for patients with low anal fistula.

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Injuries and home advantage in the NFL

In the first decade of this century players in the National Football League, the NFL community, fans, even the public at large, became aware that multiple concussions, heretofore considered inconsequential, co...

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Applying a punch with microridges in multistage deep drawing processes

The developers of high aspect ratio components aim to minimize the processing stages in deep drawing processes. This study elucidates the application of microridge punches in multistage deep drawing processes....

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The Gut Microbiome as Therapeutic Target in Central Nervous System Diseases: Implications for Stroke

Abstract

Research on commensal microbiota and its contribution to health and disease is a new and very dynamically developing field of biology and medicine. Recent experimental and clinical investigations underscore the importance of gut microbiota in the pathogenesis and course of stroke. Importantly, microbiota may influence the outcome of cerebral ischemia by modulating central nervous system antigen-specific immune responses. In this review we summarize studies linking gut microbiota with physiological function and disorders of the central nervous system. Based on these insights we speculate about targeting the gut microbiome in order to treat stroke.



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Enrichment of denitratating bacteria from a methylotrophic denitrifying culture

Abstract

Denitratation (nitrite produced from nitrate), has the potential applications in wastewater treatment by combining with ANAMMOX process. The occurrence of denitratation has been shown to be effected qualitatively by various parameters in the environment. A more quantitative understanding can be obtained using enrichment cultures in lab-scale experiments, yet information on the enrichment of functional microorganisms responsible for denitratation is lacking. In this study, a stable denitratation-dominated culture was obtained from methylotrophic denitrifying culture. The results showed that, besides the substitution of acetate for methanol, the lasting starvation following saturation of electron donor was another pivotal selection pressure that favored the growth of denitratating bacteria, which was supported by the distinctive physiological strategy involving the higher growth rate combining with larger poly-hydroxybutyrate (PHB) accumulation at sufficient electron donor situation and then manage the stress of electron donor starvation by consumpiton of the PHB. High-throughput 16S rRNA gene sequencing analysis indicated that non-methylotrophic Halomonas campisalis (48.1 %) and Halomonas campaniensis (30.4 %) dominated in the denitratating community. Moreover the denitratation was driven by the nitrate inhibiting the nirS transcription in the Halomonas species.



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Central X-ray beam correction of radiographic acetabular cup measurement after THA: an experimental study

Abstract

Purpose

Accurate assessment of cup orientation on postoperative radiographs is essential for evaluating outcome after THA. However, accuracy is impeded by the deviation of the central X-ray beam in relation to the cup and the impossibility of measuring retroversion on standard pelvic radiographs.

Method

In an experimental trial, we built an artificial cup holder enabling the setting of different angles of anatomical anteversion and inclination. Twelve different cup orientations were investigated by three examiners. After comparing the two methods for radiographic measurement of the cup position developed by Lewinnek and Widmer, we showed how to differentiate between anteversion and retroversion in each cup position by using a second plane. To show the effect of the central beam offset on the cup, we X-rayed a defined cup position using a multidirectional central beam offset. According to Murray's definition of anteversion and inclination, we created a novel corrective procedure to balance measurement errors caused by deviation of the central beam.

Results

Measurement of the 12 different cup positions with the Lewinnek's method yielded a mean deviation of \(1.8{^{\circ }}\) (95 % CI 1.3–2.3) from the original cup anteversion. The respective deviation with the Widmer/Liaw's method was \(3.2{^{\circ }}\) (95 % CI 2.4–4.0). In each case, retroversion could be differentiated from anteversion with a second radiograph. Because of the multidirectional central beam offset ( \({\pm }5\)  cm) from the acetabular cup in the cup holder ( \(25{^{\circ }}\) anteversion and \(36{^{\circ }}\) inclination), the mean absolute difference for anteversion was \(3.9{^{\circ }}\) (range \(-4.2{^{\circ }}\) to \(+4.0{^{\circ }})\) and \(0.7{^{\circ }}\) (range \(-1.2{^{\circ }}\) to \(+1.2{^{\circ }})\) for inclination. The application of our novel mathematical correction of the central beam offset reduced deviation to a mean difference of \(0.4{^{\circ }}\) for anteversion and \(0.3{^{\circ }}\) for inclination.

Conclusion

This novel calculation for central beam offset correction enables highly accurate measurement of the cup position.



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Acquisition models in intraoperative positron surface imaging

Abstract

Purpose

Intraoperative imaging aims at identifying residual tumor during surgery. Positron Surface Imaging (PSI) is one of the solutions to help surgeons in a better detection of resection margins of brain tumor, leading to an improved patient outcome. This system relies on a tracked freehand beta probe, using \(^{18}\) F-based radiotracer. Some acquisition models have been proposed in the literature in order to enhance image quality, but no comparative validation study has been performed for PSI.

Methods

In this study, we investigated the performance of different acquisition models by considering validation criteria and normalized metrics. We proposed a reference-based validation framework to perform the comparative study between acquisition models and a basic method. We estimated the performance of several acquisition models in light of four validation criteria: efficiency, computational speed, spatial accuracy and tumor contrast.

Results

Selected acquisition models outperformed the basic method, albeit with the real-time aspect compromised. One acquisition model yielded the best performance among all according to the validation criteria: efficiency (1-Spe: 0.1, Se: 0.94), spatial accuracy (max Dice: 0.77) and tumor contrast (max T/B: 5.2). We also found out that above a minimum threshold value of the sampling rate, the reconstruction quality does not vary significantly.

Conclusion

Our method allowed the comparison of different acquisition models and highlighted one of them according to our validation criteria. This novel approach can be extended to 3D datasets, for validation of future acquisition models dedicated to intraoperative guidance of brain surgery.



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Correlation of TLR4 and KLF7 in Inflammation Induced by Obesity

Abstract

Objective Recent studies have revealed a link between toll-like receptors (TLRs), Kruppel-like factors (KLFs), and the adipose tissue inflammation associated with obesity. TLR4 is associated with chronic inflammation in obesity. KLF7 is known to play an important role in the differentiation of adipocytes, but its role in visceral adipose tissue inflammation has not yet been investigated. Thus, the objective of this study was to determine the correlation of TLR4 and KLF7 in inflammation induced by obesity. Methods A total of 32 Wistar male rat subjects were fed in the center for experimental animals of Shihezi University. The rats were divided into normal control (NC) and high-fat diet (HFD) group. Surgical instruments were used to collect rats' visceral adipose tissue samples in the 10th week after HFD feeding. Ninety-five Uygur subjects between 20 and 90 years old were enrolled in the present study. The subjects were divided into two groups: the normal control group (NC, 18.0 kg/m2 ≤ BMI ≤ 23.9 kg/m2, n = 50) and the obesity group (OB, BMI ≥ 28 kg/m2, n = 45), and visceral adipose tissue was collected from the subjects. Anthropometric and clinical parameters were measured using standard procedures; biochemical indices were detected using the glucose oxidase-peroxidase method and a standardized automatic biochemistry analyzer; the plasma levels of inflammatory factors and adipocytokines were measured by enzyme-linked immunosorbent assay (ELISA); the mRNA and protein expression levels of key genes involved in the inflammatory signaling pathway were measured by real-time PCR and Western blot. Results In rats, compared with the NC group, the weight, Lee's index, waist circumference, visceral fat mass, and the plasma level of Glu, TG, FFA, and TNF-α were higher in the HFD group, while the plasma levels of LPT and APN were significantly lower in the HFD group in the 10th week. Furthermore, compared with the NC group, visceral adipose tissue's mRNA expression levels of TLR4, KLF7, and SRC were higher in the HFD group, and KLF7 was significantly positively correlated with LDL, TLR4, SRC, and IL-6 (P < 0.05). Meanwhile, in the Uygur population, the plasma levels of TG, LDL, and TNF-α in the OB group were significantly higher than those in the NC group (P < 0.05). Moreover, compared with the NC group, visceral adipose tissue's mRNA expression levels of TLR4, KLF7, and SRC were significantly higher in the OB group (P < 0.05), and KLF7 was significantly positively correlated with TC, TLR4, MYD88, SRC, and IL-6 (P < 0.05); the protein expression levels of TLR4 and KLF7 were significantly higher than those in the NC group (P < 0.05). Conclusion Higher expression of TLR4 and KLF7 may play a vital role in the process of inflammation induced by obesity in visceral adipose tissue.



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Ebola virus and arthropods: a literature review and entomological consideration on the vector role

Abstract

Ebola virus is a pathogen responsible for a severe disease that affects humans and several animal species. To date, the natural reservoir of this virus is not known with certainty, although it is believed that fruit bats (Chiroptera: Pteropodidae) play an important role in maintaining the virus in nature. Although information on viral transmission from animals to humans is not clear, the role of arthropods has come under suspicion. In this article, we review the potential role of arthropods in spreading Ebola virus, acting as mechanical or biological vectors.



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A note on the career of Donald J Winzor



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Dynamic light scattering: a practical guide and applications in biomedical sciences

Abstract

Dynamic light scattering (DLS), also known as photon correlation spectroscopy (PCS), is a very powerful tool for studying the diffusion behaviour of macromolecules in solution. The diffusion coefficient, and hence the hydrodynamic radii calculated from it, depends on the size and shape of macromolecules. In this review, we provide evidence of the usefulness of DLS to study the homogeneity of proteins, nucleic acids, and complexes of protein–protein or protein–nucleic acid preparations, as well as to study protein–small molecule interactions. Further, we provide examples of DLS's application both as a complementary method to analytical ultracentrifugation studies and as a screening tool to validate solution scattering models using determined hydrodynamic radii.



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Constrained recommendations for query visualizations

Abstract

The improvement of data storage and data acquisition techniques has led to huge accumulated data volumes in a variety of applications. International research enterprises such as the Human Genome and the Digital Sky Survey Projects are generating massive volumes of scientific data. A major challenge with these datasets is to glean insights from them to discover patterns or to originate relationships. The analysis of these massive, typically messy, and inconsistent volumes of data is indeed crucial and challenging in many application domains. Hence, the research community has introduced a number of visualizations tools to guide and help analysts in exploring the data space to extract potentially useful information. However, when working with high-dimensional datasets, identifying visualizations that show interesting variations and trends in data is not trivial: the analyst must manually specify a large number of visualizations, explore relationships among various attributes, and examine different subsets of data before discovering visualizations that are interesting or insightful. Though, exploring all possible visualizations involves complex challenges. It is a costly and time-consuming process especially when the dimensionality is high. Furthermore, the rapid growth of databases becomes multifaceted in their channels and dimensionality; thus, the transition from static analysis to real-time analytics represents a fundamental paradigm shift in the field of Big Data. Motivated by the above challenges, we propose an efficient framework called real-time scoring engine (RtSEngine) that assists analysts to limit the exploration of visualizations for a specified number of visualizations and/or certain execution time quote to recommend a set of visualizations that meet analysts' budgets. To achieve that, RtSEngine incorporates our proposed approaches to prioritize and score attributes that form all possible visualizations in a dataset based on their statistical properties such as selectivity, data distribution, and number of distinct values. Then, RtSEngine recommends the visualizations created from the top-scored attributes. Moreover, we present visualizations cost-aware techniques that estimate the retrieval and computation costs of each visualization so that analysts may discard high-cost visualizations. We show and evaluate the effectiveness and efficiency of our proposed approaches, and asses the quality of visualizations and the overhead obtained by applying our techniques on both synthetic and real datasets.



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Natural hazards in Australia: extreme bushfire

Abstract

Bushfires are one of the most frequent natural hazards experienced in Australia. Fires play an important role in shaping the landscape and its ecological dynamics, but may also have devastating effects that cause human injuries and fatalities, as well as broad-scale environmental damage. While there has been considerable effort to quantify changes in the occurrence of bushfire in Australia, a comprehensive assessment of the most extreme bushfire cases, which exact the greatest economic and environmental impacts, is lacking. In this paper we reflect upon recently developed understanding of bushfire dynamics to consider (i) historical changes in the occurrence of extreme bushfires, and (ii) the potential for increasing frequency in the future under climate change projections. The science of extreme bushfires is still a developing area, thus our conclusions about emerging patterns in their occurrence should be considered tentative. Nonetheless, historical information on noteworthy bushfire events suggests an increased occurrence in recent decades. Based on our best current understanding of how extreme bushfires develop, there is strong potential for them to increase in frequency in the future. As such there is a pressing need for a greater understanding of these powerful and often destructive phenomena.



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Genetic basis of hepatitis virus-associated hepatocellular carcinoma: linkage between infection, inflammation, and tumorigenesis

Abstract

Hepatitis virus infection is a leading cause of chronic liver disease, including cirrhosis and hepatocellular carcinoma (HCC). Although anti-viral therapies against hepatitis B virus (HBV) and hepatitis C virus (HCV) have dramatically progressed during the past decade, the estimated number of people chronically infected with HBV and/or HCV is ~370 million, and hepatitis virus-associated hepatocarcinogenesis is a serious health concern worldwide. Understanding the mechanism of virus-associated carcinogenesis is crucial toward both treatment and prevention, and the recently developed whole genome/exome sequencing analysis using next-generation sequencing technologies has contributed to unveiling the landscape of genetic and epigenetic aberrations in not only tumor tissues but also the background liver tissues underlying chronic liver damage caused by hepatitis virus infection. Several major mechanisms underlie the genetic and epigenetic aberrations in the hepatitis virus-infected liver, such as the generation of reactive oxidative stress, ectopic expression of DNA mutator enzymes, and dysfunction of the DNA repair system. In addition, direct oncogenic effects of hepatitis virus, represented by the integration of HBV-DNA, are observed in infected hepatocytes. Elucidating the whole picture of genetic and epigenetic alterations, as well as the mechanisms of tumorigenesis, will facilitate the development of efficient treatment and prevention strategies for hepatitis virus-associated HCC.



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Extracting squared speed-of-sound parameter from asymmetric nuclear collisions at high energies

Abstract

We apply the Landau hydrodynamic model in leading target/projectile nucleons and target/projectile cylinders in the multisource thermal model respectively, in asymmetric nuclear collisions. Each leading nucleon source or cylinder source is regarded as an energy reservoir to emit or produce particles and can be described by the Landau hydrodynamic model. The pseudorapidity distribution of final-state particles is in fact a sum of four Gaussian functions which correspond to the contributions of the leading target nucleons, target cylinder, projectile cylinder and leading projectile nucleons, respectively, in accordance with their central rapidities from low to high value. Based on the descriptions of the pseudorapidity distributions of final-state particles produced in proton-emulsion, deuteron-gold and gold-emulsion collisions, the squared speed-of-sound parameters for the four sources in asymmetric nuclear collisions have been extracted and shown to be approximately the same within the statistical error.



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Structural, electronic, elastic, optical, and vibrational properties of HfXSb (X = Co, Rh, Ru) half-Heusler compounds: an ab initio study

Abstract

Structural, electronic, elastic, optical, and vibrational properties of ternary half-Heusler compounds HfXSb (X = Co, Rh, Ru) were studied with means of ab initio calculations based on the density functional theory. The calculated lattice constants were in good agreement with the available data. The electronic structure and corresponding density of states (DOS) were also calculated. Indirect band gaps were observed for HfCoSb and HfRhSb. Due to some valence bands crossing the Fermi level, HfRuSb has metallic character. In addition to the electronic structure, elastic and optical properties, phonon dispersion curves and phonon DOS were calculated. A detailed comparison was made between these three half-Heusler compounds.



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Reply to Comment on “Density functional investigation on electronic structure and elastic properties of BeX at high pressure”



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Note on the Schwarzschild-phantom wormhole

Abstract

Recently, it has been shown by Lobo, Parsaei and Riazi that phantom energy with \(\omega =p_{r}/\rho <-1\) could support phantom wormholes. Several classes of such solutions have been derived by them. While the inner spacetime is represented by asymptotically flat phantom wormhole that has repulsive gravity, it is most likely to be unstable to perturbations. Hence, we consider a situation, where a phantom wormhole is somehow trapped inside a Schwarzschild sphere across a thin shell. Applying the method developed by Garcia, Lobo and Visser, we exemplify that the shell can possess zones of stability depending on certain constraints. It turns out that zones corresponding to "force" constraint are more restrictive than those from the "mass" constraint. We also enumerate the interior energy content by using the gravitational energy integral proposed by Lynden-Bell, Katz and Bi čák. It turns out that, even though the interior mass is positive, the integral implies repulsive energy. This is consistent with the phantom nature of interior matter.



http://ift.tt/2did3sb

Comment on “Density functional investigation on electronic structure and elastic properties of BeX at high pressure”

Abstract

In the article 'Density functional investigation on electronic structure and elastic properties of BeX at high pressure' published in Indian Journal of Physics (Pagare et al., Indian J Phys 90 271, 2016), Pagare et al. have investigated the structural, electronic, thermal, elastic and mechanical properties of BeX (X = Co, Ni, Cu and Pd) intermetallic compounds at high pressure. We believe that the authors committed an error during the calculation of the crystal density of these compounds which affects the calculation of some other physical properties such as longitudinal, transverse and average elastic wave velocities, and Debye temperature. In this comment, we have reexamined all data again by using the right formulae, and the values of the lattice parameters and the elastic constants obtained by Pagare et al. We have found that the crystal density values obtained by Pagare et al. have been multiplied by four and the values of longitudinal, transverse and average elastic wave velocities and Debye temperature have been divided by two.



http://ift.tt/2dImHHU

Grain-size-dependent thermal conductivity of nanocrystalline materials

Abstract

In order to study the influence of grain size and lattice strain on the thermal conductivity of nanocrystalline (NC) materials, both experimental and theoretical studies were carried out on NC copper. The NC copper samples were prepared by hot isostatic pressing of nano-sized powder particles with mean grain size of 30 nm. The thermal behaviors of the samples were measured to be 175.63–233.37 W (m K)−1 by using a laser method at 300 K, which is 45.6 and 60.6 % of the coarse-grained copper, respectively. The average grain size lies in the range of 56–187 nm, and the lattice strain is in the range of −0.21 to −0.45 % (in the direction of 111) and −0.09 to 0.92 % (in the direction of 200). In addition, a modified Kapitza resistance model was developed to study the thermal transport in NC copper. The theoretical calculations based on the presented theoretical model were in good agreement with our experimental results, and it demonstrated that the thermal conductivity of NC materials show obvious size effect. It is also evident that the decrease in the thermal conductivity of NC material can be mainly attributed to the nano-size effect rather than the lattice strain effect.



http://ift.tt/2dOAfhl

Sulfated glycosaminoglycans: their distinct roles in stem cell biology

Abstract

Sulfated glycosaminoglycan (GAG) chains are a class of long linear polysaccharides that are covalently attached to multiple core proteins to form proteoglycans (PGs). PGs are major pericellular and extracellular matrix components that surround virtually all mammalian cell surfaces, and create conducive microenvironments for a number of essential cellular events, such as cell adhesion, cell proliferation, differentiation, and cell fate decisions. The multifunctional properties of PGs are mostly mediated by their respective GAG moieties, including chondroitin sulfate (CS), heparan sulfate (HS), and keratan sulfate (KS) chains. Structural divergence of GAG chains is enzymatically generated and strictly regulated by the corresponding biosynthetic machineries, and is the major driving force for PG functions. Recent studies have revealed indispensable roles of GAG chains in stem cell biology and technology. In this review, we summarize the current understanding of GAG chain-mediated stem cell niches, focusing primarily on structural characteristics of GAG chains and their distinct regulatory functions in stem cell maintenance and fate decisions.



http://ift.tt/2dPFyT3

Targeted, Site-specific quantitation of N- and O-glycopeptides using 18 O–labeling and product ion based mass spectrometry

Abstract

The site-specific quantitation of N- and O-glycosylation is vital to understanding the function(s) of different glycans expressed at a given site of a protein under physiological and disease conditions. Most commonly used precursor ion intensity based quantification method is less accurate and other labeled methods are expensive and require enrichment of glycopeptides. Here, we used glycopeptide product (y and Y0) ions and 18O–labeling of C-terminal carboxyl group as a strategy to obtain quantitative information about fold-change and relative abundance of most of the glycoforms attached to the glycopeptides. As a proof of concept, the accuracy and robustness of this targeted, relative quantification LC-MS method was demonstrated using Rituximab. Furthermore, the N-glycopeptide quantification results were compared with a biosimilar of Rituximab and validated with quantitative data obtained from 2-AB-UHPLC-FL method. We further demonstrated the intensity fold-change and relative abundance of 46 unique N- and O-glycopeptides and aglycopeptides from innovator and biosimilar samples of Etanercept using both the normal-MS and product ion based quantitation. The results showed a very similar site-specific expression of N- and O-glycopeptides between the samples but with subtle differences. Interestingly, we have also been able to quantify macro-heterogeneity of all N- and O-glycopetides of Etanercept. In addition to applications in biotherapeutics, the developed method can also be used for site-specific quantitation of N- and O-glycopeptides and aglycopeptides of glycoproteins with known glycosylation pattern.



http://ift.tt/2cXiiMX

Characterizing cerebral and locomotor muscle oxygenation to incremental ramp exercise in healthy children: relationship with pulmonary gas exchange

Abstract

Aims

To characterize the oxygenation responses at cerebral and locomotor muscle level to incremental exercise in children and to assess the interrelationship with the pulmonary gas exchange responses.

Methods

Eighteen children (9 boys, 9 girls) (mean age 10.9 ± 1.0 years) performed incremental cycle ramp exercise to exhaustion. The concentration of cerebral and muscle oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin (by means of near-infrared spectroscopy) and pulmonary gas exchange was recorded. Cerebral and muscle O2Hb and HHb values were expressed as functions of oxygen uptake (VO2) and breakpoints were detected by means of double linear model analysis. The respiratory compensation point (RCP) was determined. The breakpoints in cerebral and muscle O2Hb and HHb were compared and correlated to RCP.

Results

The subjects reached peak power output of 105 ± 18 W and VO2peak of 43.5 ± 7.0 ml min−1 kg−1. Cerebral O2Hb increased to an intensity of 89.4 ± 5.5 %VO2peak, where a breakpoint occurred at which cerebral O2Hb started to decrease. Cerebral HHb increased slightly to 88.1 ± 4.8 %VO2peak, at which the increase was accelerated. Muscle HHb increased to 90.5 ± 4.8 %VO2peak where a leveling-off occurred. RCP occurred at 89.3 ± 4.3 %VO2peak. The breakpoints and RCP did not differ significantly (P = 0.13) and were strongly correlated (r > 0.70, P < 0.05). There were no differences between boys and girls (P = 0.43) and there was no significant correlation with VO2peak (P > 0.05).

Conclusions

It was shown that cerebral and muscle oxygenation responses undergo significant changes as work rate increases and show breakpoints in the ongoing response at high intensity (85–95 %VO2peak). These breakpoints are strongly interrelated and associated with changes in pulmonary gas exchange.



http://ift.tt/2dPFym1

Drug utilization study of systemic antifungal agents in a Brazilian tertiary care hospital

Abstract

Background The inappropriate use of systemic antifungal agents can result in unnecessary exposure, adverse events, increased microbial resistance and increased costs. Aim This study analysed the use of systemic antifungal agents and adherence to treatment guidelines for fungal infections. Setting A Brazilian tertiary hospital. Methods This cross-sectional study investigated 183 patients who were treated with systemic antifungals. Antifungal drugs were classified according to the fourth level of the Anatomical Therapeutic Chemical classification system. The appropriateness of treatments was analysed with respect to the indication, dose and potential drug–drug interactions. Descriptive and univariate statistical analyses were performed. The main outcome measure was the frequency of adherence to treatment guidelines for fungal infections. Results The number of established treatments was 320, with 163 (50.9 %) pre-emptive, 63 (19.7 %) targeted, 56 (17.5 %) empirical and 38 (11.9 %) prophylactic treatments. The overall adherence to the treatment guidelines was 29.4 %. The proportion of appropriate treatment considering indication, dosage and drug–drug interactions was 84.1, 67.8 and 47.2 %, respectively. The most commonly prescribed systemic antifungal agents were fluconazole in 170 (53.1 %), voriconazole in 43 (13.4 %) and amphotericin B deoxycholate in 36 (11.3 %) cases. Conclusion The study showed a low proportion of appropriate antifungal drug use; the dosage and drug–drug interactions criteria were the determining factors for the high percentage of non-adherence to treatment guidelines in the hospital. The profile of antifungal agents used showed the predominance of fluconazole as well as the use of new antifungal drugs.



http://ift.tt/2dVMk5A

Characteristics of cefazolin inoculum effect-positive methicillin-susceptible staphylococcus aureus infection in a multicentre bacteraemia cohort

Abstract

Cefazolin treatment failure has been observed in high-inoculum infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) with a cefazolin inoculum effect (CIE). However, data on the characteristics and risk factors for the acquisition of CIE-positive MSSA infection are scarce. CIE positivity was measured as an MIC ≥ 16 μg/ml with a high inoculum (∼5 × 107 CFU/ml). The blaZ gene type was assessed through sequence analysis. The clinical characteristics and risk factors for the acquisition of CIE-positive MSSA infection were assessed. The association between the antimicrobial susceptibility profile and CIE positivity was evaluated. A total of 303 MSSA bacteraemia cases and their corresponding isolates were collected from ten hospitals: 61 (20.1 %) isolates showed a positive CIE; 254 (83.8 %) were positive for the blaZ gene. No significant association was found between CIE positivity and the site of infection. Metastatic cancer (aOR 2.86, 95 % CI, 1.10–7.48) and recent (≤1 month) close contact with a chronically ill patient (aOR 4.69, 95 % CI, 1.76–12.50) were identified as significant risk factors for CIE-positive MSSA infection through multivariate analyses. Resistances to clindamycin (OR 3.55, 95 % CI, 1.62–7.80) and erythromycin (OR 5.00, 95 % CI, 2.50–9.99) were associated with CIE positivity, presenting high specificity (92.9 %) and a negative predictive value (82.3 %). CIE-positive MSSA constituted approximately one-fifth of MSSA bacteraemia cases. Although CIE positivity was not clinically discernible, CIE positivity was associated with clindamycin or erythromycin susceptibility. Therefore, our findings suggest that cefazolin can be used in the treatment of high-inoculum MSSA infection if the isolates are susceptible to clindamycin or erythromycin.



http://ift.tt/2dVWXcf

Technical and clinical validation of three commercial real-time PCR kits for the diagnosis of neuroborreliosis in cerebrospinal fluid on three different real-time PCR platforms

Abstract

This study reports the evaluation of the technical and clinical validation of the O-DiaBorburg kit (DIA), Borrelia burgdorferi PCR kit, ISEX (GENE), and Borrelia burgdorferi sensu lato Real-TM (SAC) for the diagnosis of neuroborreliosis in cerebrospinal fluid based on both Borrelia DNA and CSF samples from patients with clinical suspicion of neuroborreliosis. This validation study was done by analysing the kits on the Rotorgene Q (RGQ), CFX96, and LightCycler480 (LC480). For all kits, the linear range was larger on RGQ than on CFX96 and LC480. A good reproducibility was obtained for all assays on all instruments. Storage at −20 °C resulted in a decreased reproducibility for SAC. Results of the limit of detection (LOD95) experiments indicated a better sensitivity than described in the kit insert for all kits on all PCR platforms. No cross-reactivity was found for genetically related organisms nor for other pathogens which may be present in CSF. All species of the Borrelia burgdorferi sensu lato complex were detected with the GENE and SAC kits. The DIA kit failed to detect B. lusitaniae. The results seemed to indicate a better overall performance for the GENE kit on RGQ. However, its diagnostic value could not be confirmed in the clinical validation study, wherein none of the 103 CSF samples from clinical neuroborreliosis cases showed a positive real-time PCR result with the GENE kit analysed on RGQ.



http://ift.tt/2dymbuK

Emergence of New Delhi metallo-beta-lactamase 1 and other carbapenemase-producing Acinetobacter calcoaceticus-baumannii complex among patients in hospitals in Ha Noi, Viet Nam

Abstract

Acinetobacter baumannii is an important cause of multidrug-resistant hospital acquired infections in the world. Here, we investigate the presence of NDM-1 and other carbapenemases among carbapenem-resistant A. baumannii isolated between August 2010 and December 2014 from three large hospitals in Hanoi, Vietnam. We identified 23/582 isolates (4 %) (11 from hospital A, five from hospital B, and seven from hospital C) that were NDM-1 positive, and among them 18 carried additional carbapenemase genes, including seven isolates carrying NDM-1, IMP-1, and OXA-58 with high MICs for carbapenems. Genotyping indicated that NDM-1 carrying A. baumannii have expanded clonally in these hospitals. Five new STs (ST1135, ST1136, ST1137, ST1138, and ST1139) were identified. One isolate carried NDM-1 on a plasmid belonging to the N-repA replicon type; no NDM-1-positive plasmids were identified in the other isolates. We have shown the extent of the carbapenem resistance and the local clonal spread of A. baumannii carrying NDM-1 in these hospitals; coexistence of NDM-1 and IMP-1 is reported for the first time from Vietnam here, and this will further seriously limit future therapeutic options.



http://ift.tt/2dVY2RC

Mitogen-activated protein kinases (MAPKs) are modulated during Francisella tularensis infection, but inhibition of extracellular-signal-regulated kinases (ERKs) is of limited therapeutic benefit

Abstract

Francisella tularensis is a Gram-negative intracellular bacterium that causes the disease tularemia. The disease can be fatal if left untreated and there is currently no licenced vaccine available; the identification of new therapeutic targets is therefore required. Toll-like receptors represent an interesting target for therapeutic modulation due to their essential role in generating immune responses. In this study, we analysed the in vitro expression of the key mitogen-activated protein kinases (MAPKs) p38, JNK and ERK in murine alveolar macrophages during infection with F. tularensis. The phosphorylation profile of ERK highlighted its potential as a target for therapeutic modulation and subsequently the effect of ERK manipulation was measured in a lethal intranasal F. tularensis in vivo model of infection. The selective ERK1/2 inhibitor PD0325901 was administered orally to mice either pre- or post-challenge with F. tularensis strain LVS. Both treatment regimens selectively reduced ERK expression, but only the pre-exposure treatment produced decreased bacterial burden in the spleen and liver, which correlated with a significant reduction in the pro-inflammatory cytokines IFN-γ, MCP-1, IL-6, and TNF-α. However, no overall improvements in survival were observed for treated animals in this study. ERK may represent a useful therapeutic target where selective dampening of the immune response (to control the damaging pathology seen during infection) is combined with antibiotic treatment required to eradicate bacterial infection. This combination treatment strategy has been shown to be effective in other models of tularemia.



http://ift.tt/2dym0zP

Seymour “Sy” Meyerson, December 4, 1916–May 28, 2016



http://ift.tt/2dIdaR5

Learning curve in robotic rectal cancer surgery: current state of affairs

Abstract

Introduction

Robotic-assisted rectal cancer surgery offers multiple advantages for surgeons, and it seems to yield the same clinical outcomes as regards the short-time follow-up of patients compared to conventional laparoscopy. This surgical approach emerges as a technique aiming at overcoming the limitations posed by rectal cancer and other surgical fields of difficult access, in order to obtain better outcomes and a shorter learning curve.

Material and methods

A systematic review of the literature of robot-assisted rectal surgery was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was conducted in October 2015 in PubMed, MEDLINE and the Cochrane Central Register of Controlled Trials, for articles published in the last 10 years and pertaining the learning curve of robotic surgery for colorectal cancer. It consisted of the following key words: "rectal cancer/learning curve/robotic-assisted laparoscopic surgery".

Results

A total of 34 references were identified, but only 9 full texts specifically addressed the analysis of the learning curve in robot-assisted rectal cancer surgery, 7 were case series and 2 were non-randomised case-comparison series. Eight papers used the cumulative sum (CUSUM) method, and only one author divided the series into two groups to compare both. The mean number of cases for phase I of the learning curve was calculated to be 29.7 patients; phase II corresponds to a mean number 37.4 patients. The mean number of cases required for the surgeon to be classed as an expert in robotic surgery was calculated to be 39 patients.

Conclusion

Robotic advantages could have an impact on learning curve for rectal cancer and lower the number of cases that are necessary for rectal resections.



http://ift.tt/2dycbkP

Laparoscopic lavage in perforated purulent diverticulitis—is it time for definitive conclusions?



http://ift.tt/2cVifGf

The use of transureteroureterostomy during ureteral reconstruction for advanced primary or recurrent pelvic malignancy in the era of multimodal therapy

Abstract

Purpose

Cancerous involvement of a ureter is sometimes encountered in pelvic surgery for malignancy. We usually perform transureteroureterostomy (TUU) in cases of unilateral lower ureteral cancerous involvement. We report the outcomes in patients treated with TUU in our institute.

Methods

We retrospectively reviewed the medical records of 11 patients who underwent TUU between June 2006 and September 2015.

Results

The primary disease was colon cancer in five patients, rectal cancer in four, and uterine cervical cancer and ovarian cancer in one patient each. Early postoperative complications relevant to TUU occurred in four patients; however, three patients were managed conservatively and recovered quickly. Only one patient developed ureteral obstruction, which resulted from anastomotic hematoma. Follow-up periods ranged from 5 to 78 months with a median of 28 months. The median estimated glomerular filtration rate before and after TUU was 59 ml/min (range, 31–90 ml/min) and 62.0 ml/min (range, 43–127 mL/min), respectively. No patients experienced worsening of their renal function or recurrent urinary tract infection.

Conclusions

Short-term outcomes are good and long-term renal function is maintained following TUU. TUU is considered a feasible technique for ureteral reconstruction for pelvic malignancy, and TUU has great potential in the era of multimodal therapy.



http://ift.tt/2dycAnw

Laparoscopic complete mesocolic excision for right-sided colon cancer using a cranial approach: anatomical and embryological consideration

Abstract

Background

Complete mesocolic excision (CME) with central vascular ligation (CVL) should be employed for the treatment of colon cancer patients because of its superior oncological outcomes. However, this technique is technically challenging in laparoscopic right hemicolectomy because of the anatomical complexity of the transverse mesocolon.

Methods

We focused on the embryology and anatomy of the transverse mesocolon to overcome the difficulty of this surgery. The validity and efficacy of a cranial approach in achieving CME with CVL in laparoscopic right hemicolectomy was elucidated from the embryological point of view.

Results

In total, 28 consecutive patients with right-sided colon cancer were treated by laparoscopic right hemicolectomy using a cranial approach. There were no conversion to open surgery or switching to another approach. Using this approach, torsion and fusion of the transverse mesocolon, which occurred during embryological development, could be reversed and the complex anatomy of the transverse mesocolon could be simplified before performing CVL of colonic vessels.

Conclusions

A cranial approach is considered valid and useful for CME with CVL in laparoscopic right hemicolectomy from the embryological point of view.



http://ift.tt/2dPsGMI

Understanding Long-Term Outcomes Following Sepsis: Implications and Challenges

Abstract

Sepsis is life-threating organ dysfunction due to infection. Incidence of sepsis is increasing and the short-term mortality is improving, generating more sepsis survivors. These sepsis survivors suffer from additional morbidities such as higher risk of readmissions, cardiovascular disease, cognitive impairment and of death, for years following index sepsis episode. In the first year following index sepsis episode, approximately 60 % of sepsis survivors have at least one rehospitalisation episode, which is most often due to infection and one in six sepsis survivors die. Sepsis survivors also have a higher risk of cognitive impairment and cardiovascular disease contributing to the reduced life expectancy seen in this population, when assessed with life table comparisons. For optimal design of interventional trials to reduce these bad outcomes in sepsis survivors, in-depth understanding of major risk factors for these morbid events, their modifiability and a causal relationship to the pathobiology of sepsis is essential. This review highlights the recent advances, clinical and methodological challenges in our understanding of these morbid events in sepsis survivors.



http://ift.tt/2e5Wt2I

Single cell biology beyond the era of antibodies: relevance, challenges, and promises in biomedical research

Abstract

Research of the past two decades has proved the relevance of single cell biology in basic research and translational medicine. Successful detection and isolation of specific subsets is the key to understand their functional heterogeneity. Antibodies are conventionally used for this purpose, but their relevance in certain contexts is limited. In this review, we discuss some of these contexts, posing bottle neck for different fields of biology including biomedical research. With the advancement of chemistry, several methods have been introduced to overcome these problems. Even though microfluidics and microraft array are newer techniques exploited for single cell biology, fluorescence-activated cell sorting (FACS) remains the gold standard technique for isolation of cells for many biomedical applications, like stem cell therapy. Here, we present a comprehensive and comparative account of some of the probes that are useful in FACS. Further, we illustrate how these techniques could be applied in biomedical research. It is postulated that intracellular molecular markers like nucleostemin (GNL3), alkaline phosphatase (ALPL) and HIRA can be used for improving the outcome of cardiac as well as bone regeneration. Another field that could utilize intracellular markers is diagnostics, and we propose the use of specific peptide nucleic acid probes (PNPs) against certain miRNAs for cancer surgical margin prediction. The newer techniques for single cell biology, based on intracellular molecules, will immensely enhance the repertoire of possible markers for the isolation of cell types useful in biomedical research.



http://ift.tt/2cVgfha

Filamentous actin accumulates during plant cell penetration and cell wall plug formation in Phytophthora infestans

Abstract

The oomycete Phytophthora infestans is the cause of late blight in potato and tomato. It is a devastating pathogen and there is an urgent need to design alternative strategies to control the disease. To find novel potential drug targets, we used Lifeact-eGFP expressing P. infestans for high resolution live cell imaging of the actin cytoskeleton in various developmental stages. Previously, we identified actin plaques as structures that are unique for oomycetes. Here we describe two additional novel actin configurations; one associated with plug deposition in germ tubes and the other with appressoria, infection structures formed prior to host cell penetration. Plugs are composed of cell wall material that is deposited in hyphae emerging from cysts to seal off the cytoplasm-depleted base after cytoplasm retraction towards the growing tip. Preceding plug formation there was a typical local actin accumulation and during plug deposition actin remained associated with the leading edge. In appressoria, formed either on an artificial surface or upon contact with plant cells, we observed a novel aster-like actin configuration that was localized at the contact point with the surface. Our findings strongly suggest a role for the actin cytoskeleton in plug formation and plant cell penetration.



http://ift.tt/2dyaJyP

TP53 and CDKN1A mutation analysis in families with Li–Fraumeni and Li–Fraumeni like syndromes

Abstract

Li–Fraumeni and Li–Fraumeni like syndromes (LFS/LFL) represent rare cancer–prone conditions associated mostly with sarcomas, breast cancer, brain tumors, and adrenocortical carcinomas. TP53 germline mutations are present in up to 80 % of families with classic Li–Fraumeni syndrome, and in 20–60 % of families with Li–Fraumeni like phenotypes. The frequency of LFS/LFL families with no TP53 mutations detected suggests the involvement of other genes in the syndrome. In this study, we searched for mutations in TP53 in 39 probands from families with criteria for LFS/LFL. We also searched for mutations in the gene encoding the main mediator of p53 in cell cycle arrest, CDKN1A/p21, in all patients with no mutations in TP53. Eight probands carried germline disease-causing mutations in TP53: six missense mutations and two partial gene deletions. No mutations in CDKN1A coding region were detected. TP53 partial deletions in our cohort represented 25 % (2/8) of the mutations found, a much higher frequency than usually reported, emphasizing the need to search for TP53 rearrangements in patients with LFS/LFL phenotypes. Two benign tumors were detected in two TP53 mutation carriers: an adrenocortical adenoma and a neurofibroma, which raises a question about the possible implication of TP53 mutations on the development of such lesions.



http://ift.tt/2dvRVBs