Supplementation of sperm freezing medium with myoinositol improve human sperm parameters and protects it against DNA fragmentation and apoptosis

Abstract

The aim of this study is to evaluate the beneficial effect of Myoinositol (MYO) supplement in freezing media on the post thaw sperm quality. Semen samples from 40 normozoospermic men were divided into two aliquots and frozen with simple or 2 mg/mL MYO supplemented freezing medium. Post thaw process including, computer-assissted sperm analysis was used to analyze sperm motility and morphology. Reactive oxygen species was evaluated by the fluorometry of DCFH-DA, as well as total antioxidant capacity and lipid peroxidation were measured based on colorimetric assay by ELISA reader. Eventually, DNA fragmentation was assessed using TUNEL staining. MYO significantly improved progressive motility and normal morphology in treated samples (p < 0.05). Lipid peroxidation (malondialdehyde level) can be diminished in samples were frozen by MYO supplemented freezing media (p < 0.05). While MYO did not affect the amount of ROS (p > 0.05), it was associated with high values of total antioxidant capacity (p < 0.05). DNA integrity was significantly affected by MYO, as in MYO treated samples, DNA fragmentation was decreased compared to control ones (p < 0.001). The findings support the use of 2 mg/mL myoinositol supplemented freezing media in sperm cryopreservation to increase sperm quality after freezing–thawing procedures.

http://bit.ly/2FVsOqO

Incremental entity resolution process over query results for data integration systems

Abstract

Entity Resolution (ER) in data integration systems is the problem of identifying groups of tuples from one or multiple data sources that represent the same real-world entity. This is a crucial stage of data integration processes, which often need to integrate data at query-time. This task becomes even more challenging in scenarios with dynamic data sources or when a large volume of data needs to be integrated. Then, to deal with large volumes of data, new ER solutions have been proposed. One possible approach consists in performing the ER process over query results rather than in the whole set of tuples being integrated. Additionally, previous results of ER tasks can be reused in order to reduce the number of comparisons between pairs of tuples at query-time. In a similar way, indexing techniques can also be employed to help the identification of equivalent tuples and to reduce the number of comparisons between pairs of tuples. In this context, this work proposes an incremental ER process over query results. The contributions of this work are the specification, the implementation and the evaluation of the proposed incremental process. We performed some experiments and we concluded that the incremental ER at query-time is more efficient than traditional ER processes.

http://bit.ly/2sO39rE

Accumulation of hypoxia imaging probe “ 18 F-FMISO” in macrophages depends on macrophage polarization in addition to hypoxic state

Abstract

Objective

Macrophages play an essential role in immune response, and are closely related to the progression of diseases such as cancer and atherosclerosis. Macrophages polarize to M1 or M2 type, which is related to the environmental hypoxic state. Previously, we found that ¹⁸F-FMISO uptake varied according to expression levels of biomolecules such as glutathione S-transferase P1 (GST-P1), which catalyzes the conjugation of glutathione to ¹⁸F-FMISO metabolites, and multidrug resistance-associated protein 1 (MRP1), which exports glutathione-¹⁸F-FMISO metabolite conjugates out of cells. However, the relationship between macrophage polarization and ¹⁸F-FMISO accumulation remains unclear.

Methods

Mouse peritoneal macrophages were polarized to either the M1 or M2 type, and were treated with ¹⁸F-FMISO. Then, their radioactivity after a 4 h incubation period under normoxic (21% O₂) or hypoxic (1% O₂) condition was measured. GST-P1 and MRP1 expression levels were measured by qRT-PCR.

Results

M2 macrophages exhibited a significantly higher uptake of ¹⁸F-FMISO than non-polarized (M0) macrophages, whereas M1 macrophages had a significantly lower uptake than M0 macrophages (M0: 1.05 ± 0.22, M1: 0.34 ± 0.02, M2: 4.17 ± 0.36 %dose/mg protein). The GST-P1 expression level in M1 macrophages was higher than that in M2 and M0 macrophages [GST-P1/β-actin normalized by M0: 9.0 ± 3.7 (M1), 1.2 ± 0.2 (M2)]. The MRP1 expression level in M1 macrophages was significantly higher than that in M2 and M0 macrophages [MRP1/β-actin normalized by M0 macrophages: 5.1 ± 2.1 (M1), 2.8 ± 1.0 (M2)].

Conclusions

¹⁸F-FMISO accumulation in macrophages may depend on the polarization state in addition to hypoxic condition.

http://bit.ly/2MCZ2HU

Ulcerative colitis: functional analysis of the in-depth proteome

Abstract

Background

Ulcerative colitis (UC) is one major form of inflammatory bowel disease. The cause and the pathophysiology of the disease are not fully understood and we therefor aim in this study to identify important pathophysiological features in UC from proteomics data.

Methods

Colon mucosa biopsies from inflamed tissue of untreated UC patients at diagnosis and from healthy controls were obtained during colonoscopy. Quantitative protein data was acquired by bottom-up proteomics and furthermore processed with MaxQuant. The quantitative proteome data was analyzed with Perseus and enrichment data was analyzed by ClueGO for Cytoscape.

Results

The generated proteome dataset is to-date the deepest from colon mucosa biopsies with 8562 identified proteins whereof 6818 were quantified in > 70% of the samples. We report abundance differences between UC and healthy controls and the respective p values for all quantified proteins in the supporting information. From this data set enrichment analysis revealed decreased protein abundances in UC for metallothioneins, PPAR-inducible proteins, fibrillar collagens and proteins involved in bile acid transport as well as metabolic functions of nutrients, energy, steroids, xenobiotics and carbonate. On the other hand increased abundances were enriched in immune response and protein processing in the endoplasmic reticulum, e.g. unfolded protein response and signal peptidase complex proteins.

Conclusions

This explorative study describes the most affected functions in UC tissue. Our results complemented previous findings substantially. Decreased abundances of signal peptidase complex proteins in UC are a new discovery.

http://bit.ly/2MFgc7E

What Motivates Mental Health Clinicians-in-Training to Implement Evidence-Based Assessment? A Survey of Social Work Trainees

Abstract

Mental health clinicians do not consistently use evidence-based assessment (EBA), a critical component of accurate case conceptualization and treatment planning. The present study used the Unified Theory of Behavior to examine determinants of intentions to use EBA in clinical practice among a sample of Masters' level social work trainees (N = 241). Social norms had the largest effect on intentions to use EBA. Injunctive norms in reference to respected colleagues accounted for the most variance in EBA intentions. Findings differed for respondents over 29 years of age versus younger respondents. Implications for implementation strategies and further research are discussed.

http://bit.ly/2TiOxvR

Unmet Clinical Need in the Management of Locally Advanced Unresectable Lung Cancer: Treatment Strategies to Improve Patient Outcomes

Abstract

Stage III locally advanced non-small cell lung cancer (LA NSCLC) comprises the most heterogeneous group of patients, accounts for one-third of patients with lung cancer, and is unresectable at presentation. Multiple treatment approaches have evolved over the past few decades focusing on timing of chemoradiation (concurrent vs. sequential) and sequencing of therapy (induction vs. consolidation). Concurrent chemoradiation (CCRT) emerged as the standard of care for the majority of the patients worldwide. Despite improvements in median and overall survival (OS) using the concurrent approach, the rate of distant failure remains high. Consolidation with chemotherapy or targeted agents, adding more radiation dose, or induction chemotherapy did not improve OS. With continued research on defining optimal radiation doses and schedules and integrating novel systemic agents, immunotherapy consolidation has renewed optimism. Synergistic use of radiation and immunotherapy can prevent micrometastatic disease and reduce local failure and may have an abscopal effect in addition to survival benefits. The PACIFIC study reported an absolute progression-free survival benefit of 11.2 months with durvalumab consolidation after standard CCRT compared with placebo. The OS data with durvalumab consolidation are encouraging. Durvalumab is the only approved immunotherapy for unresectable stage III LA NSCLC. Improved survival confirms the definitive role of durvalumab as an effective adjuvant therapy after CCRT with no new safety signals. However, the potential mechanisms driving interaction between immunotherapy and chemoradiotherapy require definitive investigation. These mechanisms may help define the timing of immunotherapy initiation as neoadjuvant, adjuvant, or consolidation and maintenance therapy after progression.

Funding

AstraZeneca Pharma India Limited.

http://bit.ly/2RUf8mh

Saccharomyces boulardii CNCM I-745 plus sequential therapy for Helicobacter pylori infections: a randomized, open-label trial

Abstract

Aim

To determine the effect of Saccharomyces boulardii CNCM I-745 (S. boulardii) plus sequential therapy on Helicobacter pylori (H. pylori) eradication rate.

Methods

This open-label prospective study randomized (1:1) patients with confirmed H. pylori infection to standard sequential therapy of twice-daily (bid) omeprazole 20 mg plus amoxicillin 1 g for 5 days, followed by bid omeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg for the next 5 days (control group), or sequential therapy plus bid S. boulardii 250 mg (experimental group). Adverse events (AEs) were recorded throughout the study, and the H. pylori eradication rate was determined 4 weeks after treatment.

Results

The study was conducted from May 2013 to May 2016 and included 199 patients (51.3% male; mean age 44.6 ± 13.6 years). The H. pylori eradication rate was higher in the experimental group than the control group (86.0% vs. 74.7%; P = 0.02). Compared with the control group, patients in the experimental group experienced a significantly lower overall incidence of AEs (17.0% vs. 55.7%; p < 0.001) and the incidence of antibiotic-associated diarrhea (2.0% vs. 46.4%; P = 0.02). The experimental group showed improved treatment compliance over the 10-day study period compared with the control group (95.0% vs. 91.2%, P < 0.001).

Conclusion

Addition of S. boulardii to sequential therapy improved H. pylori eradication rate and reduced the incidence of treatment-associated AEs in Moroccan patients with H. pylori infection.

http://bit.ly/2Th6kDG

Experimental validation of the 3-parameter critical power model in cycling

Abstract

Purpose

The three-parameter model of critical power (3-p) implies that in the severe exercise intensity domain time to exhaustion (T_lim) decreases hyperbolically with power output starting from the power asymptote (critical power, ẇ_cr) and reaching 0 s at a finite power limit (ẇ₀) thanks to a negative time asymptote (k). We aimed to validate 3-p for short T_lim and to test the hypothesis that ẇ₀ represents the maximal instantaneous muscular power.

Methods

Ten subjects performed an incremental test and nine constant-power trials to exhaustion on an electronically braked cycle ergometer. All trials were fitted to 3-p by means of non-linear regression, and those with T_lim greater than 2 min also to the 2-parameter model (2-p), obtained constraining k to 0 s. Five vertical squat jumps on a force platform were also performed to determine the single-leg (i.e., halved) maximal instantaneous power.

Results

T_lim ranged from 26 ± 4 s to 15.7 ± 4.9 min. In 3-p, with respect to 2-p, ẇ_cr was identical (177 ± 26 W), while curvature constant W' was higher (17.0 ± 4.3 vs 15.9 ± 4.2 kJ, p < 0.01). 3-p-derived ẇ₀ was lower than single-leg maximal instantaneous power (1184 ± 265 vs 1554 ± 235 W, p < 0.01).

Conclusions

3-p is a good descriptor of the work capacity above ẇ_cr up to T_lim as short as 20 s. However, since there is a discrepancy between estimated ẇ₀ and measured maximal instantaneous power, a modification of the model has been proposed.

http://bit.ly/2HKHDhU

Loss of Endothelial Laminin α5 Exacerbates Hemorrhagic Brain Injury

Abstract

Endothelial cells make laminin-411 and laminin-511. Although laminin-411 is well studied, the role of laminin-511 remains largely unknown due to the embryonic lethality of lama5^−/− mutants. In this study, we generated endothelium-specific lama5 conditional knockout (α5-TKO) mice and investigated the biological functions of endothelial lama5 in blood-brain barrier (BBB) maintenance under homeostatic conditions and the pathogenesis of intracerebral hemorrhage (ICH). First, the BBB integrity of α5-TKO mice was measured under homeostatic conditions. Next, ICH was induced in α5-TKO mice and their littermate controls using the collagenase model. Various parameters, including injury volume, neuronal death, neurological score, brain edema, BBB integrity, inflammatory cell infiltration, and gliosis, were examined at various time points after injury. Under homeostatic conditions, comparable levels of IgG or exogenous tracers were detected in α5-TKO and control mice. Additionally, no differences in tight junction expression, pericyte coverage, and astrocyte polarity were found in these mice. After ICH, α5-TKO mice displayed enlarged injury volume, increased neuronal death, elevated BBB permeability, exacerbated infiltration of inflammatory cells (leukocytes, neutrophils, and mononuclear cells), aggravated gliosis, unchanged brain edema, and worse neurological function, compared to the controls. These findings suggest that endothelial lama5 is dispensable for BBB maintenance under homeostatic conditions but plays a beneficial role in ICH.

http://bit.ly/2FXAUPC

Propagation of future climate conditions into hydrologic response from coastal southern California watersheds

Abstract

As a biodiverse region under a Mediterranean climate with a mix of highly developed and natural watersheds, coastal Santa Barbara County (SB), located in southern California, is susceptible to the hydrologic impacts of climate change. This study investigates the potential changes in hydro-meteorological variables in this region as well as their societal and ecological implications for projected climate conditions during the twenty-first century. Daily streamflow ensembles from 135 coastal watersheds for the period 2021–2100 are developed using the Hillslope River Routing (HRR) model forced with downscaled precipitation and temperature projections derived from 10 climate models in the Coupled Model Inter-Comparison Project, Phase 5, and two emission scenarios (Representative Concentration Pathways, RCP, 4.5 and 8.5). Analysis of the projected ensemble precipitation and streamflow series relative to historical conditions (1961–2000) shows (i) minimal change in annual precipitation (median change within ±3%); (ii) an altered seasonal rainfall distribution with a decrease in rainfall at the beginning of the rainy season (Oct–Dec), an increase during the Jan–Mar period, and a decrease at the end of the season (Apr–Jun); (iii) increases in the magnitude and frequency of large storms (> 36 mm/day) which combined with a shorter rainy season, lead to increases in annual peak flows; and (iv) the propagation of the altered precipitation characteristics resulting in nonlinear changes in the magnitude and variability of annual maximum discharges (i.e., mean, standard deviation, skew) impacting estimated return period discharges (e.g., estimated 100-year flood discharges for the period 2061–2100 under 8.5 increase by up to 185%). While these results are specific to southern coastal California, the nature of nonlinear hydrologic response to altered precipitation characteristics underscores the value of regional studies investigating potential impacts of climate projections on streamflow dynamics.

http://bit.ly/2sPGoU6

Radiological evaluation of low-grade glioma: time to embrace quantitative data?

http://bit.ly/2DGKaW9

Influence of pregnancy on glioma patients

Abstract

Background

Data about the influence of pregnancy on progression-free survival and overall survival of glioma patients are sparse and controversial. We aimed at providing further evidence on this relation.

Methods

The course of 18 glioma patients giving birth to 23 children after tumor surgery was reviewed and compared to the course of 18 nulliparous female patients matched for tumor diagnosis including molecular markers, extent of resection, and tumor location.

Results

Tumor pathology was astrocytoma, oligodendroglioma, and ependymoma in 9, 6, and 3 patients, respectively. Time interval between tumor resection and delivery was 5.3 ± 4.4 years. All newborns were healthy after uneventful deliveries. Tumor progression was diagnosed before pregnancy in 4 patients and during pregnancy in 1 patient, and 4 patients displayed progressive disease 31.0 ± 11 months after delivery. Three of these latter patients underwent second surgery, whereas resection of recurrent tumor had been performed in 2 women before pregnancy. Among nulliparous patients, 9 women suffered from tumor progression, resulting in re-operation in 7 patients and/or further adjuvant treatment in 6 cases. Progression-free survival did not differ between patients with and patients without children (p = 0.4). Moreover, in both groups, median overall survival was not reached after a mean follow-up period of 9.7 ± 5.7 years in glioma patients who gave birth to a child and 8.9 ± 4.2 years in nulliparous glioma patients.

Conclusion

Pregnancy does not seem to influence the clinical course of glioma patients. Likewise, glioma seems not to have an impact on delivered children's health.

http://bit.ly/2UqpwPG

Obstructive sleep apnea and atherosclerosis—update 2019

Abstract

Obstructive sleep apnea (OSA) is a common disorder that has been associated with an increased risk of atherosclerosis and its clinical manifestations. While treatment with continuous positive airway pressure (CPAP) has been shown to exert several beneficial effects on cardiovascular disease and prognosis in observational studies, CPAP was not effective in three recent randomized controlled trials unless it was used for more than 4 hours of sleep.

http://bit.ly/2UoUAiy

Vaskuläre Konsequenzen schlafbezogener Erkrankungen

http://bit.ly/2DG5b3i

Restless legs syndrome in childhood and adolescence

Abstract

Background

The prevalence of restless legs syndrome (RLS) is lower among children than adults. This could be due to RLS manifestation later in life or false diagnoses in children caused by symptom similarity to other diseases such as attention deficient hyperactivity disorder (ADHD).

Objective

The aim of this study was to test the reliability and validity of a questionnaire designed to identify RLS-related symptoms in children and adolescents.

Materials and methods

The questionnaire was designed for two age groups (6–12 and 13–18 years). It was distributed among 11 pediatric RLS patients and 22 healthy children and adolescents (control group). The control group answered the questionnaire twice (M1, M2; 14-day separation). Reliability was analyzed descriptively and with Spearman correlation coefficients, intraclass correlation coefficients (ICC), and test–retest variability (TRV). An index was calculated by transferring the 12 answers concerning RLS symptoms into a coding system, grading each answer between −2 and 2 and adding the grades to an index value. Low index values hint at the absence of RLS-related symptoms. Student's t‑test was used to test the difference between healthy controls and pediatric patients.

Results

In the control group, 84% of answer pairs were identical between M1 and M2. Mean TRV was 8% (range: 2–16%), Spearman correlation coefficient 0.762, and ICC 0.754 (confidence interval: 0.473–0.899). Comparison between controls and pediatric RLS patients showed that RLS patients had significantly higher (p < 0.001) index values (mean ± SD: 18.8 ± 4) compared to controls (mean ± SD: −3.8 ± 7.6).

Conclusion

The questionnaire can distinguish between supposedly healthy and RLS-diagnosed children and adolescents in most cases. Nonetheless, the questionnaire cannot be used alone as a diagnostic instrument.

http://bit.ly/2UoUA22

Dunbar syndrome—a reappraisal

Abstract

Dunbar syndrome also called as median arcuate ligament syndrome is a rare cause of angina abdominis. Diagnosis can be made with CT angiography or magnetic resonance imaging (MRI). Surgery is the gold standard treatment. This is an instance of Dunbar syndrome who was assessed for abdominal torment and was alluded from gastroenterology department for vascular and surgical intervention.

http://bit.ly/2COYyKr

Bioleaching of Heavy Metals from Pig Manure Employing Indigenous Sulfur-Oxidizing Bacteria: Effects of Solid Content

Abstract

The effects of solid content (10–80 g/L) on the bioleaching of heavy metals (HMs) from pig manure (PM) were investigated using indigenous sulfur-oxidizing bacteria. The results showed that an increase in solid content increased the PM buffering capacity, which slowed the rates of pH reduction, ORP increase, and sulfur oxidation and decreased the solubilization efficiency of HMs from PM. Approximately 75–99% of Cu, 76–99% of Zn, and 55–88% of Mn were leached from PM with solid contents of 10–80 g/L after 28 days of bioleaching. However, the content of HMs in bioleached manure did not meet the requirement for agricultural application when the solid content was ≥ 60 g/L after 28 days of bioleaching. The solubilization of HMs from PM was well-described by a kinetic equation. Regression analysis showed that Cu solubilization was primarily controlled by ORP, and pH seemed to be the sole factor responsible for the solubilization of Zn and Mn. Additionally, nutrient (N, P, K, and organic matter) loss significantly increased when PM solid content decreased from 40 to 20 g/L. Therefore, the recommended solid content for the bioleaching of HMs from PM is 40 g/L.

http://bit.ly/2Wq8bbj

Ultra-high-resolution subtraction CT angiography in the follow-up of treated intracranial aneurysms

Abstract

In subtraction CT angiography (CTA), a non-contrast CT acquisition is subtracted from a contrast-enhanced CTA acquisition. Subtraction CTA can be applied in the detection, classification, and follow-up of intracranial aneurysms and is advantageous over conventional angiography because of its non-invasive nature, shorter examination time, and lower costs. Recently, an ultra-high-resolution CT scanner has been introduced in clinical practice offering an in-plane spatial resolution of up to 0.234 mm, approaching the resolution as seen during conventional invasive digital subtraction angiography (DSA). The twofold increase in spatial resolution as compared to a conventional CT scanner could improve the evaluation of small vascular structures and, coupled with dedicated post-processing techniques, further reduce metal artifacts. Technical considerations using a state-of-the-art high-resolution subtraction CTA protocol are discussed for application in the follow-up of surgical and endovascular treated intracranial aneurysms.

http://bit.ly/2G4INSF

Strategic research agenda for biomedical imaging

Abstract

This Strategic Research Agenda identifies current challenges and needs in healthcare, illustrates how biomedical imaging and derived data can help to address these, and aims to stimulate dedicated research funding efforts.

Medicine is currently moving towards a more tailored, patient-centric approach by providing personalised solutions for the individual patient. Innovation in biomedical imaging plays a key role in this process as it addresses the current needs for individualised prevention, treatment, therapy response monitoring, and image-guided surgery.

The use of non-invasive biomarkers facilitates better therapy prediction and monitoring, leading to improved patient outcomes. Innovative diagnostic imaging technologies provide information about disease characteristics which, coupled with biological, genetic and -omics data, will contribute to an individualised diagnosis and therapy approach.

In the emerging field of theranostics, imaging tools together with therapeutic agents enable the selection of best treatments and allow tailored therapeutic interventions.

For prenatal monitoring, the use of innovative imaging technologies can ensure an early detection of malfunctions or disease.

The application of biomedical imaging for diagnosis and management of lifestyle-induced diseases will help to avoid disease development through lifestyle changes.

Artificial intelligence and machine learning in imaging will facilitate the improvement of image interpretation and lead to better disease prediction and therapy planning.

As biomedical imaging technologies and analysis of existing imaging data provide solutions to current challenges and needs in healthcare, appropriate funding for dedicated research is needed to implement the innovative approaches for the wellbeing of citizens and patients.

http://bit.ly/2sShMKE

Abdominal applications of ultrasound fusion imaging technique: liver, kidney, and pancreas

Abstract

Fusion imaging allows exploitation of the strengths of all imaging modalities simultaneously, eliminating or minimizing the weaknesses of every single modality. Ultrasound (US) fusion imaging provides benefits in real time from both the dynamic information and spatial resolution of the normal US and the high-contrast resolution and wider field of view of the other imaging methods. US fusion imaging can also be associated with the use of different ultrasound techniques such as color Doppler US, elastography, and contrast-enhanced US (CEUS), for better localization and characterization of lesions. The present paper is focused on US fusion imaging technologies and clinical applications describing the possible use of this promising imaging technique in the liver, kidney, and pancreatic pathologies.

http://bit.ly/2MDUhxC

The value of CSF flow studies in the management of CSF disorders in children: a pictorial review

Abstract

CSF flow disorders are frequently encountered in children. The advent of MR technology with the emergence of new pulse sequences allowed better understanding of CSF flow dynamics. In this pictorial review, we aim to conduct a comprehensive review of the MR protocol used to study CSF flow disorders and to discuss the utility of each pulse sequence in the adopted protocol. We will focus on the key anatomical structures that should be examined to differentiate hydrocephalus form ventricular dilatation ex-vacuo. The MR features of obstructive and communicating hydrocephalus will be discussed, in addition to the manifestations of CSF disorders associated with posterior fossa malformations (Dandy-Walker malformation, Chiari, and Blake's pouch cyst). Moreover, the value of MRI in the assessment of patients following interventional procedures (ventriculoperitoneal shunt and third ventriculostomy) will be addressed.

http://bit.ly/2sOTmBF

Advanced endoscopic interventions on the pancreas and pancreatic ductal system: a primer for radiologists

Abstract

In recent years, technological advancements including endoscopic ultrasound (EUS) guidance and availability of specifically designed stents further expanded the indications and possibilities of interventional endoscopy. Although technically demanding and associated with non-negligible morbidity, advanced pancreatic endoscopic techniques now provide an effective minimally invasive treatment for complications of acute and chronic pancreatitis.

Aiming to provide radiologists with an adequate familiarity, this pictorial essay reviews the indications, techniques, results and pre- and post-procedural cross-sectional imaging appearances of advanced endoscopic interventions on the pancreas and pancreatic ductal system. Most of the emphasis is placed on multidetector CT and MRI findings before and after internal drainage of pseudocysts and walled-off necrosis via EUS-guided endoscopic cystostomy, and on stent placement to relieve strictures or disruption of the main pancreatic duct, respectively in patients with chronic pancreatitis and disconnected pancreatic duct syndrome.

http://bit.ly/2FUOzXX

Dynamic magnetic resonance imaging of the female pelvic floor—a pictorial review

Abstract

Pelvic floor dysfunctions represent a range of functional disorders that frequently occur in adult women, carrying a significant burden on the quality of life, and its incidence tends to increase attending to the expected aging of the population. Pelvic floor dysfunctions can manifest as incontinence, constipation, and prolapsed pelvic organs. Since pelvic floor weakness is frequently generalized and clinically underdiagnosed, imaging evaluation is of major importance, especially prior to surgical correction. Given some interobserver variability of soft-tissue measurements, MR defecography allows a noninvasive, radiation-free, multiplanar dynamic evaluation of the three pelvic compartments simultaneously and with high spatial and temporal resolution. Both static/anatomic and dynamic/functional findings are important, since pelvic disorders can manifest as whole pelvic floor weakness/dysfunction or as an isolated or single compartment disorder. Imaging has a preponderant role in accessing pelvic floor disorders, and dynamic MR defecography presents as a reliable option, being able to evaluate the entire pelvic floor for optimal patient management before surgery. The purpose of this article is to address the female pelvic anatomy and explain the appropriate MR Defecography protocol, along with all the anatomic points, lines, angles, and measurements needed for a correct interpretation, to later focus on the different disorders of the female pelvic floor, illustrated with MR defecography images, highlighting the role of this technique in accessing these pathologic conditions.

http://bit.ly/2sOUO6W

Obstructive sleep apnea phenotypes in men based on characteristics of respiratory events during polysomnography

Abstract

Purpose

The upper airway (UA) anatomical collapsibility, UA muscle responsiveness, breathing control, and/or arousability are important contributing factors for obstructive sleep apnea (OSA). Differences in clinical manifestations of OSA are believed to reflect interactions among these factors. We aimed to classify OSA patients into subgroups based on polysomnographic (PSG) variables using cluster analysis and assess each subgroup's characteristics.

Methods

Men with moderate or severe OSA and without any concomitant heart or psychosomatic disease were recruited. A hierarchical cluster analysis was performed using variables including fraction of apnea, respiratory event duration, minimum oxygen saturation, arousal rate before termination, and frequency of respiratory events in the supine position. The impact of sleep stages or body position on PSG variables was also evaluated in each cluster.

Results

A total of 210 men (mean age, 50.0 years, mean body mass index, 27.4 kg/m²) were studied. The three subgroups that emerged from the analysis were defined as follows: cluster 1 (high fraction of apnea and severe desaturation (20%)), cluster 2 (high fraction of apnea and long event duration (31%)), and cluster 3 (low fraction of apnea (49%)). There were differences in the body mass index and apnea type between the three clusters. Sleep stages and/or body position affected PSG variables in each cluster.

Conclusions

Patients with OSA could be divided into three distinct subgroups based on PSG variables. This clustering may be used for assessing the pathophysiology of OSA to tailor individual treatment other than continuous positive airway pressure therapy.

http://bit.ly/2DF4qau

Algal sorbent derived from Sargassum horneri for adsorption of cesium and strontium ions: equilibrium, kinetics, and mass transfer

Abstract

An algal sorbent derived from Sargassum horneri was prepared and used to adsorb cesium and strontium ions from aqueous solution. The phenomenological mathematical models associated to the predicted equilibrium isotherms were developed to determine the rate-limiting steps of the adsorption process. The maximum adsorption capacity of cesium ion and strontium ion was calculated to be 0.358 and 1.72 mmol g⁻¹, respectively. The adsorption kinetics followed to the pseudo-second-order equation. It was found that adsorption of cesium or strontium ions onto the active sites of the biosorbent was the rate-limiting step. In addition, the external mass transfer and the internal mass transfer cannot be neglected for the adsorption of strontium ion based on the error analysis. The functional groups relevant to the adsorption were carboxyl and sulfate groups.

http://bit.ly/2CPWGRu

Effects of Musical Training and Hearing Loss on Fundamental Frequency Discrimination and Temporal Fine Structure Processing: Psychophysics and Modeling

Abstract

Several studies have shown that musical training leads to improved fundamental frequency (F₀) discrimination for young listeners with normal hearing (NH). It is unclear whether a comparable effect of musical training occurs for listeners whose sensory encoding of F₀ is degraded. To address this question, the effect of musical training was investigated for three groups of listeners (young NH, older NH, and older listeners with hearing impairment, HI). In a first experiment, F₀ discrimination was investigated using complex tones that differed in harmonic content and phase configuration (sine, positive, or negative Schroeder). Musical training was associated with significantly better F₀ discrimination of complex tones containing low-numbered harmonics for all groups of listeners. Part of this effect was caused by the fact that musicians were more robust than non-musicians to harmonic roving. Despite the benefit relative to their non-musicians counterparts, the older musicians, with or without HI, performed worse than the young musicians. In a second experiment, binaural sensitivity to temporal fine structure (TFS) cues was assessed for the same listeners by estimating the highest frequency at which an interaural phase difference was perceived. Performance was better for musicians for all groups of listeners and the use of TFS cues was degraded for the two older groups of listeners. These findings suggest that musical training is associated with an enhancement of both TFS cues encoding and F₀ discrimination in young and older listeners with or without HI, although the musicians' benefit decreased with increasing hearing loss. Additionally, models of the auditory periphery and midbrain were used to examine the effect of HI on F₀ encoding. The model predictions reflected the worsening in F₀ discrimination with increasing HI and accounted for up to 80 % of the variance in the data.

http://bit.ly/2SdY0au

Prolonged shedding of type 55 human adenovirus in immunocompetent adults with adenoviral respiratory infections

Abstract

Human adenovirus (HAdV) is a common pathogen causing respiratory infections with outbreaks reported in the military and community. However, little information is available on the shedding kinetics. We performed a prospective study of immunocompetent adults confirmed with HAdV respiratory infection by multiplex real-time PCR during an outbreak of HAdV-55. Consecutive respiratory specimens of sputum or nasopharyngeal swab were collected from each patient every 2 days. Viral load was measured by real-time quantitative PCR. Of 32 enrolled patients, 27 (84.4%) had pneumonia. Five patients (15.6%) received cidofovir. Viral load was highest in the earliest samples at 8.69 log₁₀ copies/mL. In a linear regression model, viral load declined consistently in a log-linear fashion at the rate of − 0.15 log₁₀ copies/mL per day (95% confidence interval (CI): − 0.18, − 0.12; R² = 0.32). However, the regression model estimated the viral shedding duration to be 55 days. The rate of decline in viral load did not differ between patients who received cidofovir and who did not. Patients with prominent respiratory symptoms or extensive involvement on chest radiograph had higher volume of viral excretion. Prolonged viral shedding was observed in otherwise healthy adults with HAdV-55 respiratory infection. This finding should be considered in the establishment of infection control and prevention strategies.

http://bit.ly/2MDnQj7

Effect of two-dimensional graphene oxide on the phase change stability of carbon nanotubes and their application for thermal energy storage

Abstract

Acid-treated carbon nanotubes have a significant improvement on the phase change behavior of nanofluids through the elimination of supercooling degrees and improvement on thermal conductivity. However, it has been found that these carbon nanotubes aggregated after a single phase change cycle. In this study, this problem has been successfully solved by the incorporation of graphene oxide with acid-treated multi-walled carbon nanotubes (of diameters from 10 to 15 nm) to form an interpenetrated structure of nanofillers with good stability of at least 90 cycles. The efficacy of the carbon nanotubes and graphene oxide nanofillers with different ratios has been demonstrated to shorten the phase change duration of the nanofluids with insignificant reduction to their latent heat. The synergy of two different dimensional nanofillers prevented the aggregation of acid-treated carbon nanotubes without the use of surfactants and achieved high-energy storage capacity and reliability.

http://bit.ly/2DG4Z43

Pattern of sleep dysfunction in systemic lupus erythematosus: a cluster analysis

Abstract

Objectives

To investigate how the different components of sleep dysfunction described in SLE patients combine together in sleep clusters.

Methods

We conducted a cross-sectional study on a perspective cohort of 79 SLE patients (mean age 8.2 ± 14.3 years). Sleep was evaluated using Pittsburgh Sleep Quality Index (PSQI). Clusters were defined using the single components of PSQI in a hierarchical clustering model. We used Beck Depression Inventory, Hamilton Anxiety Rating Scale, and Medical Outcomes Study Short Form 36 (SF36) to measure depressive symptoms, anxiety, and quality of life, respectively.

Results

Three sleep clusters were identified. The cluster 1 (N = 47) is characterized by the lowest values of PSQI total score. The cluster 2 (N = 21) presents higher values of sleep latency, but sleep duration similar to cluster 1. In cluster 3 (N = 11), we found sleep latency increased as in cluster 2, but the highest values of PSQI total score and reduced sleep duration. Scores of anxiety and sedentary time were higher in clusters 2 and 3 than in cluster 1. Cluster 3 presented the highest scores of depression and reduced mental and physical components of SF36.

Conclusions

The combination of different sleep components in SLE patients allowed us to identify three patterns of dysfunction: a first cluster with better sleep latency and duration, a second with increased sleep latency but conserved duration, and a third with impairment of both latency and duration. The stratification of sleep disorders in clusters might be useful for the personalization of therapy in relation to sleep cluster membership.

http://bit.ly/2WqXB3N

The role of location in visual feature binding

Abstract

Location appears to play a vital role in binding discretely processed visual features into coherent objects. Consequently, it has been proposed that objects are represented for cognition by their spatiotemporal location, with other visual features attached to this location index. On this theory, the visual features of an object are only connected via mutual location; direct binding cannot occur. Despite supporting evidence, some argue that direct binding does take over according to task demands and when representing familiar objects. The current study was developed to evaluate these claims, using a brief memory task to test for contingencies between features under different circumstances. Participants were shown a sequence of three items in different colours and locations, and then asked for the colour and/or location of one of them. The stimuli could either be abstract shapes, or familiar objects. Results indicated that location is necessary for binding regardless of the type of stimulus and task demands, supporting the proposed structure. A follow-up experiment assessed an alternate explanation for the apparent importance of location in binding; eye movements may automatically capture location information, making it impossible to ignore and suggesting a contingency that is not representative of cognitive processes. Participants were required to maintain fixation on half of the trials, with an eye tracker for confirmation. Results indicated that the importance of location in binding cannot be attributed to eye movements. Overall, the findings of this study support the claim that location is essential for visual feature binding, due to the structure of object representations.

http://bit.ly/2B5nyNi

SCN1A and SCN2A polymorphisms are associated with response to valproic acid in Chinese epilepsy patients

Abstract

Purpose

There is a large inter-individual variation in the efficacy of valproic acid (VPA) against epilepsy. The genetic polymorphism influence of sodium channels on VPA response remains a matter of debate. The aim of the study was to explore the effect of SCN1A and SCN2A gene polymorphisms on VPA response in the treatment of epilepsy among Chinese patients.

Methods

A total of 354 epileptic patients with VPA treatment were genotyped for five single nucleotide polymorphisms (SNP), including SCN1A rs10188577 T>C, rs2298771 T>C, rs3812718 G>A, and SCN2A rs2304016 A>G, rs17183814 G>A. A binary logistic regression analysis was performed to evaluate the association of genotype with VPA antiepileptic effects, adjusting the influence of confounding factors.

Results

Genotype distributions of all selected SNPs were consistent with the Hardy–Weinberg equilibrium in epilepsy patients. SCN1A rs3812718 and SCN2A rs2304016 were found to be significantly associated with VPA response, both in monotherapy and in VPA-based polytherapy. Patients with the rs3812718 A allele were more frequently seen in the VPA-responsive group (P < 0.05), and the rs2304016 G allele was related to an increased risk of resistance to VPA therapy (P < 0.05).

Conclusions

Our study revealed that SCN1A rs3812718 and SCN2A rs2304016 polymorphisms might be markers of VPA response in Chinese epilepsy patients.

Trial registration

ChiCTR-1800016477

http://bit.ly/2RSmDdw

Isolation of Bacterial Consortia that Induced Corrosion of Zirconium Alloys

Abstract

The aim of the present study was to isolate several bacterial consortia from a soil sample and to establish if they could colonize zirconium-tin alloy, such as Zircaloy-4. Two bacterial consortia containing aerobic heterotrophic bacteria and anaerobic sulfate-reducing bacteria were isolated from a soil sample. The aerobic heterotrophic bacteria exhibited a higher capability to utilize different sole carbon sources, as compared with anaerobic sulfate-reducing bacteria. Based on a morphological, biochemical, and molecular analysis, bacterial isolates were identified as Pseudomonas putida IBB_HA1, Pseudomonas aeruginosa IBB_HA2, Achromobacter spanius IBB_HA3, Citrobacter freundii IBB_SR1, Citrobacter youngae IBB_SR2, and Citrobacter braakii IBB_SR3. Isolated bacterial consortia which possess distinct DNA fingerprints were able to form biofilms and colonize the surface of zirconium-tin alloy coupons, although the colonization of coupons by the aerobic heterotrophic bacteria or anaerobic sulfate-reducing bacteria alone was lower compared with that observed when the coupon was immersed in a mixture of both bacterial consortia. Coupons immersed in these bacterial consortia revealed changes in the surface characteristics, which can facilitate or accelerate zirconium-tin alloy corrosion. The accumulation of corrosion products on coupons surface was less significant when the coupons were immersed solely in aerobic heterotrophic bacteria or anaerobic sulfate-reducing bacteria, compared with that observed when the coupon was immersed in a mixture of both bacterial consortia.

http://bit.ly/2MBu8Qg

Insertions of antihypertensive peptides and their applications in pharmacy and functional foods

Abstract

Hypertension is a worldwide health problem. It is the main cardiovascular risk factor and affects about 31% of the world's adult population. The drugs used to control hypertension may cause side effects; for this reason, there are many investigations focused on searching for alternatives to control or prevent this disease through diet. For example, many peptides have demonstrated antihypertensive effects. The insertion of bioactive peptides is a biotechnological implement used to improve the nutraceutical properties of proteins. This work reviews the current data on the insertion of antihypertensive peptides (AHPs) into food proteins, the systems used to produce the AHPs, the advantages and disadvantages between them, the parameters to produce them at major scales, and their potential applications in pharmacy and functional foods.

http://bit.ly/2FVk2t3

Suppression of miR-93-5p inhibits high-risk HPV-positive cervical cancer progression via targeting of BTG3

Abstract

This study explores the role of miR-93-5p in high-risk HPV-positive (HR-HPV) cervical cancer by targeting of BTG3. Cervical tissues were collected from 332 patients with conditions of chronic cervicitis (n = 42), low-grade cervical intraepithelial neoplasia (CIN I, n = 51), CIN II (n = 49), CIN III (n = 43), cervical cancer (n = 90), and normal cervical tissues (n = 57). HR-HPV DNA was detected by Hybrid Capture 2, and the expressions of miR-93-5p and BTG3 were determined by qRT-PCR and Western blot. The target relationship between miR-93-5p and BTG3 was verified by dual-luciferase reporter gene assay. HPV-positive cervical cancer cells (CaSki and HeLa) were divided into control, NC, inhibitor, BTG3, and mimic + BTG3 groups. CCK-8, Annexin V-APC/PI, and Transwell assays were applied to evaluate cell biological activities. MiR-93-5p was positively related but BTG3 was inversely related to HR-HPV infection. Additionally, miR-93-5p expression was negatively correlated with BTG3 expression in cervical cancer tissues infected with HR-HPV. HPV-positive cervical cancer cells showed higher miR-93-5p and lower BTG3 levels than negative cells. CaSki and HeLa cells in the inhibitor group showed increased BTG3 compared with the control group. After transfection with miR-93-5p inhibitor or BTG3 activation plasmid, proliferation and metastasis were inhibited, but apoptosis was promoted. The mimic + BTG3 group showed increased cell proliferation and metastasis but decreased cell apoptosis compared with the BTG3 group. Upregulated miR-93-5p was positively related but downregulated BTG3 was inversely related to HR-HPV infection, and inhibition of miR-93-5p may have blocked HPV-positive cervical cancer development by targeting of BTG3.

http://bit.ly/2DFB9wI

White Matter Integrity and Early Outcomes After Acute Ischemic Stroke

Abstract

Chronic white matter structural injury is a risk factor for poor long-term outcomes after acute ischemic stroke (AIS). However, it is unclear how white matter structural injury predisposes to poor outcomes after AIS. To explore this question, in 42 AIS patients with moderate to severe white matter hyperintensity (WMH) burden, we characterized WMH and normal-appearing white matter (NAWM) diffusivity anisotropy metrics in the hemisphere contralateral to acute ischemia in relation to ischemic tissue and early functional outcomes. All patients underwent brain MRI with dynamic susceptibility contrast perfusion and diffusion tensor imaging within 12 h and at day 3–5 post stroke. Early neurological outcomes were measured as the change in NIH Stroke Scale score from admission to day 3–5 post stroke. Target mismatch profile, percent mismatch lost, infarct growth, and rates of good perfusion were measured to assess ischemic tissue outcomes. NAWM mean diffusivity was significantly lower in the group with early neurological improvement (ENI, 0.79 vs. 0.82 × 10⁻³, mm²/s; P = 0.02). In multivariable logistic regression, NAWM mean diffusivity was an independent radiographic predictor of ENI (β = − 17.6, P = 0.037). Median infarct growth was 118% (IQR 26.8–221.9%) despite good reperfusion being observed in 65.6% of the cohort. NAWM and WMH diffusivity metrics were not associated with target mismatch profile, percent mismatch lost, or infarct growth. Our results suggest that, in AIS patients, white matter structural integrity is associated with poor early neurological outcomes independent of ischemic tissue outcomes.

http://bit.ly/2SdCAuf

Subdural haematoma in neonates following forceps-assisted delivery: case series and review of the literature

Abstract

Purpose

Subdural haematoma (SDH) is a recognised complication of forceps-assisted delivery (FAD). There are no guidelines regarding its management. This study aims to provide a better insight into the management and outcomes of neonatal SDH post-FAD.

Methods

Retrospective review of our neonatal database and systematic review of the literature for neonatal cases that presented with SDH after FAD. Retrospective neurosurgical database search for cases of neonatal SDH post-FAD managed in our unit between January 2007 and January 2017. Systematic review of the literature was performed using PRISMA guidelines. The inclusion criteria are as follows: (1) neonates; (2) forceps-assisted delivery; (3) evidence of SDH on imaging, with or without other traumatic lesions.

Results

A literature search yielded nine studies with 30 patients meeting our inclusion criteria. In addition, four cases were identified from our institutional database. Forty-two percent (n = 14) had their SDH managed surgically, with subsequent full neurological recovery in 57%. In comparison, 95% (n = 18) of the conservatively managed patients made a full recovery. Hydrocephalus was present in 1/19 and 11/14 of the conservatively managed and surgically managed patients respectively.

Conclusions

Conservative management can lead to a full neurological recovery in SDH following FAD in neonates. However, a significant minority may still need neurosurgical intervention for the SDH or subsequent hydrocephalus; therefore, we advocate early transfer to a specialist neuroscience centre.

http://bit.ly/2sNkeC2

Recent intensification of the seasonal rainfall cycle in equatorial Africa revealed by farmer perceptions, satellite-based estimates, and ground-based station measurements

Abstract

Smallholder farmers and livestock keepers in sub-Saharan Africa are on the frontlines of climate variability and change. Yet, in many regions, a paucity of weather and climate data has prevented rigorous assessment of recent climate trends and their causes, thereby limiting the effectiveness of forecasts and other services for climate adaptation. In rainfed systems, farmer perceptions of changing rainfall and weather patterns are important precursors for annual cropping decisions. Here, we propose that combining such farmer perceptions of trends in seasonal rainfall with satellite-based rainfall estimates and climate station data can reduce uncertainties regarding regional climatic trends. In western Uganda, a rural and climatically complex transition zone between eastern and central equatorial Africa, data from 980 smallholder households suggest distinct changes in seasonal bimodal rainfall over recent decades, specifically wetter rainy seasons and drier dry seasons. Data from three satellite-based rainfall products beginning in 1983 largely corroborate respondent perceptions over the last 10–20 years, particularly in the southernmost sites near Queen Elizabeth National Park. In addition, combining all three information sources suggests an increasing trend in annual rainfall, most prominently in the north near Murchison Falls National Park over the past two decades; this runs counter to recent research asserting the presence of a drying trend in the region. Our study is unique in evaluating and cross-validating these multiple data sources to identify climatic change affecting people in a poorly understood region, while providing insights into regional-scale climate controls.

http://bit.ly/2DCApYU

MRI and Blood Flow in Human Arteries: Are There Any Adverse Effects?

Abstract

Purpose

To explore if there are any adverse effects on blood flow in human beings when they are exposed to high or ultra high intensity magnetic fields in MRI, by investigating both qualitatively and quantitatively the effects of such fields on the velocity of blood and medically significant hemodynamic wall parameters such as wall shear stress (WSS), oscillatory shear index (OSI) and relative residence time (RRT) in four human large arteries.

Methods

Blood flow in an artery is approximated as a flow through a uniform circular tube with rigid porous walls and the well-known McDonalds model is employed by using pressure gradient waveforms reported in the medical literature.

Results

No significant change in the above parameters is observed up to 3T in all these arteries except a discernible change in the velocity and RRT in the pulmonary artery. Very significant changes are noticed in the above parameters beyond 8T in the pulmonary artery. The common hypothesis that low WSS and high OSI co-locate is not acceptable.

Conclusions

Our results suggest that the clinical consequences are to be carefully considered before exposing human beings to ultra high field MRI. It may not be appropriate to conclude anything about the effect of magnetic field on blood flow in human beings based on experimental studies on animals, which is one of the reasons for the contradicting reports found in the literature. A slip condition at the wall which is appropriate to hemodynamics is yet to be developed.

http://bit.ly/2MD4PgP

A novel intermittent negative air pressure device ameliorates obstructive sleep apnea syndrome in adults

Abstract

Purpose

Patients with obstructive sleep apnea syndrome (OSAS) have difficulties in compliance with continuous positive airway pressure (CPAP) and the treatment outcome is heterogeneous. We proposed a proof-of-concept study of a novel intermittent negative air pressure (iNAP®) device for physicians to apply on patients who have failed or refused to use CPAP.

Methods

The iNAP® device retains the tongue and the soft palate in a forward position to decrease airway obstruction. A full nightly usage with the device was evaluated with polysomnography. Subgrouping by baseline apnea–hypopnea index (AHI) and body mass index (BMI) with different treatment response criteria was applied to characterize the responder group of this novel device.

Results

Thirty-five patients were enrolled: age 41.9 ± 12.2 years (mean ± standard deviation), BMI 26.6 ± 4.3 kg/m², AHI 41.4 ± 24.3 events/h, and oxygen desaturation index (ODI) 40.9 ± 24.4 events/h at baseline. AHI and ODI were significantly decreased (p < 0.001) by the device. Patients with moderate OSAS, with baseline AHI between 15 to 30 events/h, achieved 64% response rate; and non-obese patients, with BMI below 25 kg/m², achieved 57% response rate, with response rate defined as 50% reduction in AHI from baseline and treated AHI lower than 20. There were minimal side effects reported.

Conclusions

In a proof-of-concept study, the device attained response to treatment as defined, in more than half of the moderate and non-obese OSAS patients, with minimal side effects.

http://bit.ly/2ThSGQQ

Image-based clustering and connected component labeling for rapid automated left and right ventricular endocardial volume extraction and segmentation in full cardiac cycle multi-frame MRI images of cardiac patients

Abstract

A rapid method for left and right ventricular endocardial volume segmentation and clinical cardiac parameter calculation from MRI images of cardiac patients is presented. The clinical motivation is providing cardiologists a tool for assessing the cardiac function in a patient through the left ventricular endocardial volume's ejection fraction. A new method combining adapted fuzzy membership-based c-means pixel clustering and connected regions component labeling is used for automatic segmentation of the left and right ventricular endocardial volumes. This proposed pixel clustering with labeling approach avoids manual initialization or user intervention and does not require specifying the region of interest. This method fully automatically extracts the left and right ventricular endocardial volumes and avoids manual tracing on all MRI image frames in the complete cardiac cycle from systole to diastole. The average computational processing time per frame is 0.6 s, making it much more efficient than deformable methods, which need several iterations for the evolution of the snake or contour. Accuracy of the automated method presented herein was validated against manual tracing-based extraction, performed with the guidance of cardiac experts, on several MRI frames. Dice coefficients between the proposed automatic versus manual traced ventricular endocardial volume segmentations were observed to be 0.9781 ± 0.0070 (for left ventricular endocardial volume) and 0.9819 ± 0.0058 (for right ventricular endocardial volume), and the Pearson correlation coefficients were observed to be 0.9655 ± 0.0206 (for left ventricular endocardial volume) and 0.9870 ± 0.0131 (for right ventricular endocardial volume).

Graphical abstract

The left ventricular endocardial volume segmentation methodology illustrated as a series of algorithms.

http://bit.ly/2G3rOQC

Developing professional confidence in the art of prescribing—a randomized controlled study on structured collegial discussions during internship

Abstract

Purpose

To evaluate whether an educational intervention based on collegial discussions on patient cases could increase interns' professional confidence in prescribing.

Methods

In a randomized controlled study at Sahlgrenska University Hospital, Gothenburg, Sweden, 69 interns (median age: 29 years, 54% female) were allocated to an intervention or control group. The intervention consisted of two 3-h seminars based on collegial discussions of patient cases focused on performing medication reviews. This included reconciling the drug treatment and ascertaining that it is reasonable given the patient's current health status, as well as tips on practical handling of the medical records system and integrated decision support. Self-assessed confidence in performing medication reviews was evaluated with questionnaires distributed at baseline and at 6-month follow-up.

Results

Fifty-seven (83%) interns completed the questionnaires. Although the opposite was found at baseline, intervention interns, in comparison with controls, at follow-up, were more confident in performing medication reviews (4.3 ± 0.9 vs. 3.6 ± 1.3, P = 0.034; 1 = completely disagree to 5 = completely agree). At follow-up, the intervention participants had increased their confidence in prescribing to a greater extent compared with the control participants, including performing medication reviews as well as taking responsibility for the medication list at discharge: + 1.5/+ 1 vs ± 0 on the 5-point agreement scale (all P ≤ 0.01). Among other positive outcomes, the intervention increased the interns' awareness of adverse effects as a potential cause of symptoms and their confidence in withdrawing a medication.

Conclusion

Structured collegial discussions on pharmacotherapy, even of a relatively short duration, can increase junior physicians' professional confidence in prescribing medicines.

http://bit.ly/2CPtuKl

Diversity and Spatiotemporal Distribution of Fungal Endophytes Associated with Citrus reticulata cv. Siyahoo

Abstract

Endophytic fungi are characterized as microorganisms found within internal tissues of living plants without any immediate, overtly negative effects. The present study was carried out to isolate, taxonomically characterize and determine the spatiotemporal distribution of endophytic fungi associated with leaf, stem, trunk, and root of mandarin (Citrus reticulata cv. Siyahoo). To do so, the sampling program was done seasonally in four geographically isolated mandarin growing areas of Hormozgan province of Iran, including Siyahoo, Ahmadi, Sikhoran, and Roudan. In total, 702 fungal isolates were obtained from leaf, stem, trunk, and root of healthy mandarin trees divided into 26 distinct morphotypes based on morphological characteristics. The morphotypes were taxonomically characterized through phylogenetic analysis of the ITS1-5.8S-ITS4 rDNA region sequences. Accordingly, 10 different fungal orders from 5 fungal classes were identified, i.e., Saccharomycetes (Saccharomycetales), Eurotiomycetes (Eurotiales), Dothideomycetes (Capnodiales, Pleosporales, Dothideales), and Sordariomycetes (Diaporthales, Hypocreales, Microascales, Togniniales), all from Ascomycota, which represented 97.2% and Ustilaginomycetes (Ustilaginales) from Basidiomycota which represented 2.8% of the isolates. The Aureobasidium pullulans, Penicillium citrinum, and Dothideomycetes sp. were the most frequent isolates. The trunk and leaf showed the highest and lowest total colonization frequency and species richness of endophytic fungi, respectively, in all sampling periods. The results showed that the colonization frequency of endophytes in Hormozgan province was higher in autumn than that in spring, winter, and summer. The trunk showed the maximum diversity of endophytes over all seasons. The Shannon–Wiener (H′) and Simpson indices had significant correlation with sampling cites and tissue type and the maximum value of Shannon and Simpson indices (H′ = 3.05 and 1 − D = 0.94) was found in the specimens collected from Siyahoo. In conclusion, the three factors (season, location, and tissue type) all in together could determine fungal endophyte composition of C. reticulata.

http://bit.ly/2FXw7hg

Determinants of stem cell lineage differentiation toward chondrogenesis versus adipogenesis

Abstract

Adult stem cells, also termed as somatic stem cells, are undifferentiated cells, detected among differentiated cells in a tissue or an organ. Adult stem cells can differentiate toward lineage specific cell types of the tissue or organ in which they reside. They also have the ability to differentiate into mature cells of mesenchymal tissues, such as cartilage, fat and bone. Despite the fact that the balance has been comprehensively scrutinized between adipogenesis and osteogenesis and between chondrogenesis and osteogenesis, few reviews discuss the relationship between chondrogenesis and adipogenesis. In this review, the developmental and transcriptional crosstalk of chondrogenic and adipogenic lineages are briefly explored, followed by elucidation of signaling pathways and external factors guiding lineage determination between chondrogenic and adipogenic differentiation. An in-depth understanding of overlap and discrepancy between these two mesenchymal tissues in lineage differentiation would benefit regeneration of high-quality cartilage tissues and adipose tissues for clinical applications.

http://bit.ly/2sSCOZj

Etiology of aortic dissection

Abstract

We discuss the etiology of aortic dissection (AD) from various points of view. The development of AD requires two pathological conditions: medial degeneration and mechanical wall stress. First, histopathological findings of medial degeneration are hypothesized to be due to a loss of elastic fibers and interconnecting elastic fibers. Damage to the vasa vasorum plays a key role in creating an entry site. The clinical causes of medial degeneration include hypertension, aortic aneurysms, obstructive sleep apnea, and connective tissue disorders. Second, mechanical wall stress is supposedly induced by shear stress caused by blood flow, together with hypertension and aortic root movement. Further investigation is necessary in the search for mechanisms responsible for medial degeneration prior to AD development.

http://bit.ly/2FUN2RG

Behandlungsstrategien beim Oropharynxkarzinom

Abstract

Hintergrund

Das Oropharynxkarzinom (OPSCC) stellt aufgrund seiner weltweiten Inzidenzzunahme und der Assoziation mit dem humanen Papillomavirus HPV-16, aber auch chronischem Tabak‑/Alkoholkonsum eine genetisch heterogene Tumorgruppe mit hoher prognostischer Diversität dar.

Ziel

Die Übersichtsarbeit versucht, die aktuelle Sicht der Therapie und Prävention des OPSCC in Hinblick auf die Assoziation mit HPV16 darzustellen.

Material und Methoden

Die Übersicht erfolgt auf der Basis der aktuellen relevanten Literatur sowie der derzeit laufenden Studien.

Ergebnisse und Diskussion

Das OPSCC stellt sich als sehr komplexe, genetisch heterogene und daher detailliert anzusehende Gruppe von Kopf-Hals-Tumoren dar. Die derzeit widersprüchliche Studienlage, die auf dem Boden retrospektiver Daten aktuelle TNM-Klassifikation („8th Edition") und die abzuwartenden prospektiven Daten zur Therapiedeintensivierung ermahnen aktuell eher zu einer konservativen Therapiebetrachtung. Durch die aktuellen Impfempfehlungen ist jetzt auch die HPV-Impfung für Jungen analog zu den Mädchen in Deutschland zugelassen.

http://bit.ly/2G7MdE7

Humane Papillomaviren und das Oropharynxkarzinom

Zusammenfassung

Hintergrund

Das humane Papillomavirus (HPV) gehört zur Familie der Papillomaviren. Basierend auf dem karzinogenen Potenzial der Viren erfolgt die Einteilung in Niedrig- und Hochrisikotypen. Niedrigrisikotypen sind verantwortlich für genitale Papillome und die rekurrierende respiratorische Papillomatose, während HPV-Hochrisikotypen weltweit 5 % der Karzinome induzieren. HPV gilt als sexuell übertragbare Erkrankung und ist, neben der Entstehung anogenitaler Karzinome, im Kopf-Hals-Bereich für die Pathogenese des HPV-assoziierten Oropharynxkarzinoms (OPSCC) verantwortlich.

Methoden

Diese Arbeit basiert auf einer selektiven Literaturrecherche in der Datenbank PubMed zum Thema HPV-assoziierte OPSCC.

Ergebnisse

Die Inzidenz dieser vorrangig in der Tonsille sowie im Zugengrund lokalisierten HPV-assoziierten Kopf-Hals-Karzinome steigt. Aufgrund der virusgetriebenen Karzinogenese unterscheiden sich HPV-assoziierte OPSCC hinsichtlich genetischer und molekularbiologischer Aspekte von den noxenassoziierten OPSCC und weisen im Vergleich eine signifikant verbesserte Prognose auf. Der Nachweis einer HPV-Assoziation erfolgt u. a. über den immunhistochemischen Nachweis einer Überexpression des Surrogatmarkers p16, welcher seit 2017 in der 8. Auflage der TNM-Klassifikation maligner Tumoren berücksichtigt wird. Bisher wird bei der Wahl der Therapie nicht aufgrund des HPV-Status unterschieden, welches in beiden Entitäten zu einer hohen Nebenwirkungsrate führt.

Schlussfolgerung

Um zukünftig eine Therapiedeeskalation bestimmter Patientengruppen zu ermöglichen, wurden prognostische Modelle zur Risikostratifizierung entwickelt. Zur Überwachung des Krankheitsverlaufs sowie der frühzeitigen Detektion eines Therapieversagens werden aktuell Screeningmethoden wie die Flüssigbiopsie auf ihre Validität geprüft. Die HPV-Impfung, welche der primären Prophylaxe einer Tumorentstehung dient, wird für Mädchen sowie seit kurzem auch für Jungen im Alter von 9 bis 14 Jahren von der Ständigen Impfkommission (STIKO) empfohlen.

http://bit.ly/2FTii3l

Crack growth resistance in rubber composites with controlled Interface bonding and interphase content

Abstract

The distinction between abrasion resistance of carbon black and silica reinforced tire tread compounds has drawn attention to the indispensable role of interfacial phenomena on crack growth resistance of rubber composites. Attempts to determine the dependence of interface bonding (from covalent to non-covalent) on crack growth resistance of rubber composites are insufficient without knowledge of the contributions resulting from the interphase (i.e. the volume of rubber chains with restricted mobility). For highly-filled rubbers, the interphase is mainly formed by strong filler-filler interaction and entrapment of rubbers among filler aggregates. Working on the silane-treated silica reinforced rubber, here the alkyl length and the grafting density of silane are systematically controlled to fabricate filler systems with desired surface energy, specified filler-filler interaction and definite trapped-rubber/interphase content. At equal surface energy of fillers one could then change the interface bonding from covalent to non-covalent and study the role of interface on the crack growth resistance. After analyzing the tearing energy of the resulting composites, it was found that the primary factor affecting the fracture strength of highly filled rubbers is the content of the trapped-rubber. The type of interface bonding shared a secondary contribution to the tearing energy values. A slip-stick fracture pattern was observed for the composite with the covalently-bonded interface. A mechanistic model ascribing the relation between the tearing energy and the controlling parameters of the fracture was also proposed.

http://bit.ly/2sQSsEA

Prospective Observational Cohort Study to Describe the Use of Panitumumab in Combination with Chemotherapy in Real-World Clinical Practice for Patients with Wild-Type RAS mCRC

Abstract

Introduction

This study aimed to better understand panitumumab use in real-life clinical practice in first- and second-line treatment of metastatic colorectal cancer in five European countries.

Methods

This is a combined analysis of two observational, non-interventional prospective cohort studies, one of which was conducted in Germany and France, the other in Bulgaria, Czech Republic, and Hungary. The studies observed patients with wild-type [Kirsten] rat sarcoma viral oncogene homolog ([K]RAS/RAS) metastatic colorectal cancer (mCRC), who had been treated with panitumumab in combination with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in the first line or with panitumumab combined with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in the second line following fluoropyrimidine-based chemotherapy. The planned duration of observation was 12 months from the first dose of panitumumab.

Results

A total of 332 patients treated with panitumumab + FOLFOX in the first line and 94 patients treated with panitumumab + FOLFIRI in the second line were analyzed. The median number of panitumumab infusions was 10.0 in first-line FOLFOX patients and 11.5 in second-line FOLFIRI patients; the median duration of panitumumab exposure was 5.7 and 6.9 months, respectively. The unadjusted overall response rate (complete or partial response) in patients with available post-baseline response assessment (n = 290) was 51.7% in first-line FOLFOX and 44.9% in second-line FOLFIRI patients. In the first-line setting, resectability was achieved in 9.3%. Reported hospitalizations were mostly cancer-related visits such as scheduled anticancer treatment administrations, tumor assessment visits, or interventions. The majority of adverse drug reactions were skin disorders, with 75.3% in first-line FOLFOX patients and 72.3% in second-line FOLFIRI patients.

Conclusion

Overall, the study results show that treatment patterns, clinical efficacy, and the safety profile of panitumumab in routine clinical practice were comparable to those in randomized controlled trials. The relatively low skin toxicity rate could be attributed to increasing experience in managing panitumumab-associated rash and some degree of underreporting.

Funding

Amgen.

http://bit.ly/2G5P1BW

Effect Oral Administration Ampicillin on the Ecological Balance of rat Enterococcal gut Microbiota

Abstract

The main objective of this work is to investigate the impact of oral administration of ampicillin on the ecological balance of enterococci in the intestinal microbiota of rats during a treatment and a post-treatment. The results have showed that the treated animals excreted significantly higher percentages of resistant enterococci compared to the control group (P ≤ 0.05) during the treatment and after the treatment. The most predominant species selected after the treatment began were Enterococcus faecium. The MICs for ampicillin for all isolates of E. faecium were 32 to 64 µg/mL, with the exception of two strains (TR1LBMB, TR5LBMB), were found to be highly resistant (MICs ≥ 128 µg/mL). Quantification of ampicillin in faeces by the RT-HPLC showed that the significant increase in the number of ampicillin-resistant enterococci was associated with the gradual accumulation of high levels of unabsorbed ampicillin in the faeces. Our results suggest that ampicillin treatment can now be understood as a side effect contributing to the increase in the number of resistant Enterococcus strains, particularly E. faecium strains, recognized as important nosocomial pathogens.

http://bit.ly/2S9n1ns

Microalbuminuria in Chronic Obstructive Pulmonary Disease with and Without Co-morbidities

http://bit.ly/2CQhOHb

GEORG SCHMORL PRIZE OF THE GERMAN SPINE SOCIETY (DWG) 2018: combined inflammatory and mechanical stress weakens the annulus fibrosus: evidences from a loaded bovine AF organ culture

Abstract

Purpose

The pathomechanism of annulus fibrosus (AF) failure is still unknown. We hypothesise that mechanical overload and an inflammatory microenvironment contribute to AF structural weakening. Therefore, the objective of this study was to investigate the influence of these factors on the AF, particularly the translamellar bridging network (TLBN) which connects the AF lamellae.

Methods

A bovine AF organ culture (AF-OC) model of standardised AF rings was used to study the individual and combined effects of cyclic tensile strain (CTS) and IL-1β (1 ng/mL) culture medium supplementation. AF-OCs were analysed for PGE₂ production (ELISA) and deposition of IL-6, COX-2, fibrillin, and MMP3 in the tissue (immunohistochemistry, IHC). The mechanical strength of the TLBN was evaluated using a peel test to measure the strength required to separate an AF segment along a lamellar bound.

Results

The combination of CTS + IL-1β led to a significant increase in PGE₂ production compared to Control (p < 0.01). IHC evaluations showed that the CTS + IL-1β group exhibited higher production of COX-2 and MMP3 within the TLBN regions compared to the adjacent lamellae and a significant increase in IL-6 ratio compared to Control (p < 0.05). A significant decrease in the annular peel strength was observed in the CTS + IL1β group compared to Control (p < 0.05).

Conclusion

Our findings suggest that CTS and IL-1β act synergistically to increase pro-inflammatory and catabolic molecules within the AF, particularly the TLBN, leading to a weakening of the tissue. This standardised model enables the investigation of AF/TLBN structure–function relationship and is a platform to test AF-focused therapeutics.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

http://bit.ly/2RmCJqP

Reply to Holgado et al.: Comment on “Review of WADA Prohibited Substances: Limited Evidence for Performance-Enhancing Effects”

http://bit.ly/2ThUolh

Comment on “Review of WADA Prohibited Substances: Limited Evidence for Performance-Enhancing Effects”

http://bit.ly/2B9laoH

Bone Bruises Associated with Anterior Cruciate Ligament Injury as Indicators of Injury Mechanism: A Systematic Review

Abstract

Background

Anterior cruciate ligament (ACL) injury is one of the most common injuries in sports, and the injury mechanisms are not completely clear. Bone bruises seen on magnetic resonance imaging (MRI) following ACL injuries may provide significant information for determining ACL injury mechanisms.

Objective

The aim was to determine ACL injury mechanisms through an evaluation of locations of bone bruises associated with ACL injury.

Methods

A search for related articles in PubMed and the EBSCO Sport Database was performed using selected search strings from inception to August 6, 2018. Original studies with specified bone bruise locations identified using MRI technology were reviewed.

Results

A total of 12 studies with 589 patients were selected for review. A total of 471 bone bruises in the lateral tibial plateau were reported. Of these bone bruises, 409 (87%) occurred in the posterior section. A total of 242 bone bruises in the medial tibial plateau were reported. Of these bone bruises, 208 (86%) occurred in the posterior section. A total of 266 bone bruises in the lateral femoral condyle were reported. Of these bone bruises, 65 (25%) and 184 (69%) occurred in the anterior and central sections, respectively. A total of 105 bone bruises in the medial femoral condyle were reported. Of these bone bruises, 49 (47%) and 41 (39%) occurred in the anterior and central sections, respectively.

Conclusions

Bone bruise location patterns indicate that tibial anterior translation relative to the femur was a primary injury mechanism in the majority of ACL injuries selected in this review, and that the maximal knee valgus apparently occurred after tibial anterior translation sufficient to injure the ACL. Bone bruise location patterns also indicate knee hyper-extension as another mechanism of non-contact ACL injury.

http://bit.ly/2Tky36G

Laparoskopische Minorresektionen der Leber als ambulante Operationen – eine Pilotstudie

http://bit.ly/2G3bOhM

Efficacy of new intermittent abdominal pressure ventilator for post-ischemic cervical myelopathy ventilatory insufficiency

Abstract

Non-invasive ventilation (NIV) is the treatment of choice for patients symptomatic for respiratory muscle dysfunction. It can normalize gas exchange and provide up to continuous non-invasive ventilator support (CNVS) as an alternative to intubation and tracheotomy. It is usually provided via non-invasive facial interfaces or mouthpieces, but these can be uncomfortable and uncosmetic. The intermittent abdominal pressure ventilator (IAPV) has been used for diurnal ventilatory support since 1938 but has been off the market since about 1990. Now, however, with greater emphasis on non-invasive management, a new IAPV is available. A patient with chronic ventilatory insufficiency post-ischemic cervical myelopathy, dependent on sleep NVS since 2003, developed symptomatic daytime hypercapnia for which he also used diurnal NVS via nasal pillows. However, he preferred not having to use facial interfaces. When not using diurnal NVS he was becoming dyspnoeic. Diurnal use of an IAPV was introduced. Arterial blood gas analysis using the IAPV decreased his blood pH from 7.45 to 7.42, PaCO₂ from 58 to 37 mmHg, and improved PaO₂ from 62 to 92 mmHg. At discharge, the patient used the IAPV 8 h/day with improved mood and quality of life. Consequently, he returned to work as a painter.

http://bit.ly/2SdSEMC

Animal Behavior, Population Biology and the Modern Synthesis (1955–1985)

Abstract

This paper examines the history of animal behavior studies after the synthesis period. Three episodes are considered: the adoption of the theory of natural selection, the mathematization of ideas, and the spread of molecular methods in behavior studies. In these three episodes, students of behavior adopted practices and standards developed in population ecology and population genetics. While they borrowed tools and methods from these fields, they made distinct uses (inclusive fitness method, evolutionary theory of games, emphasis on individual selection) that set them relatively apart and led them to contribute, in their own way, to evolutionary theory. These episodes also highlight some limitations of "conjunction narratives" centered on the relation between a discipline and the modern synthesis. A trend in conjunction narratives is to interpret any development related to evolution in a discipline as an "extension," an "integration," or as a "delayed" synthesis. I here suggest that this can lead to underestimate discontinuities in the history of evolutionary biology.

http://bit.ly/2HNYQHh

Animal Behavior, Population Biology and the Modern Synthesis (1955–1985)

Abstract

This paper examines the history of animal behavior studies after the synthesis period. Three episodes are considered: the adoption of the theory of natural selection, the mathematization of ideas, and the spread of molecular methods in behavior studies. In these three episodes, students of behavior adopted practices and standards developed in population ecology and population genetics. While they borrowed tools and methods from these fields, they made distinct uses (inclusive fitness method, evolutionary theory of games, emphasis on individual selection) that set them relatively apart and led them to contribute, in their own way, to evolutionary theory. These episodes also highlight some limitations of "conjunction narratives" centered on the relation between a discipline and the modern synthesis. A trend in conjunction narratives is to interpret any development related to evolution in a discipline as an "extension," an "integration," or as a "delayed" synthesis. I here suggest that this can lead to underestimate discontinuities in the history of evolutionary biology.

http://bit.ly/2HNYQHh

Tolvaptan: A Review in Autosomal Dominant Polycystic Kidney Disease

Abstract

Tolvaptan [Jynarque^® (USA); Jinarc^® (EU, Canada); Samsca^® (Japan)] is a highly selective vasopressin V₂ receptor antagonist approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD). In the phase III TEMPO 3:4 trial, 3 years' treatment with tolvaptan slowed the increase in total kidney volume (TKV) and the decline in renal function relative to placebo. The composite secondary endpoint of time to investigator-assessed clinical progression also favoured tolvaptan over placebo. Although tolvaptan did not demonstrate a sustained disease-modifying effect on TKV over the longer term in the TEMPO 4:4 extension trial, the effect of tolvaptan in slowing renal function decline was maintained for a further 2 years. The phase III REPRISE trial confirmed the efficacy of tolvaptan in patients with later-stage ADPKD. Most of the adverse events commonly observed with tolvaptan (e.g. polyuria, nocturia, polydipsia, thirst) are consistent with its pharmacological activity. In the TEMPO trials, tolvaptan was also associated with idiosyncratic hepatotoxicity which was reversible on discontinuation of the drug. Although the use of tolvaptan requires careful consideration and balancing of benefits and risks, it provides a valuable treatment option to slow the progression of ADPKD in patients at risk of or with evidence of rapidly progressing disease.

http://bit.ly/2HADKMf

Adherence to CPAP with a nasal mask combined with mandibular advancement device versus an oronasal mask: a randomized crossover trial

Abstract

Purpose

Evidence for the management of CPAP-treated obstructive sleep apnea suggests that oronasal masks reduce mouth leaks at the expense of higher pressures and poorer adherence. Some authors have proposed the use of mandibular advancement devices in combination with nasal masks to address this. The aim of this study was to assess adherence to CPAP after 1 month's use of a nasal mask with a mandibular advancement device and to compare adherence with an oronasal mask.

Methods

A randomized crossover trial design to assess whether a mandibular advancement device combined with a nasal mask would improve CPAP adherence compared to an oronasal mask.

Results

There was no improvement in CPAP adherence and self-reported interface-related pain was significantly higher with the combined treatment.

Conclusions

Although the combined treatment reduced pressures, likely by improving upper airway patency, it may only be appropriate for a small number of patients due to associated discomfort.

Trial registration

NCT01889472

http://bit.ly/2Ukw8Pp

Polysomnographic characteristics of adolescents with asthma and low risk for sleep-disordered breathing

Abstract

Purpose

The aim of this study was to describe the polysomnographic characteristics of adolescents with asthma who are at low risk for sleep-disordered breathing (SDB) based on the Pediatric Sleep Questionnaire (PSQ).

Methods

Overnight polysomnography was performed on 85 adolescents with asthma and a score < 0.33 on the PSQ. The Asthma Control Questionnaire was used to define "well-controlled" versus "inadequately controlled" asthma.

Results

Mean age of participants was 14.5 ± 1.6 years (range, 11 to 17 years), 63.5% were girls, 57.6% were Caucasians, and the mean body mass index percentile was 65.1 ± 26.5. Asthma was well-controlled in 51.7% of the adolescents and inadequately controlled in 15.3%. Mean sleep efficiency (SE) was 88.0 ± 11.1%, and 24.7% had SE < 85%. Mean wakefulness after sleep onset (WASO) was 40.9 ± 44.0 min, and the mean arousal index was 10.8 ± 5.6 per hour. The mean apnea/hypopnea index (AHI) was 2.3 ± 4.2, and 29.4% of participants had SDB (defined by an AHI ≥ 2). Compared with normative values, adolescents with asthma had more nocturnal awakenings and WASO, and less REM sleep. SDB risk was higher in boys [odds ratio = 4.6 (confidence interval 1.4–14.7), p = 0.01]. Asthma control did not impact sleep and respiratory parameters, with no differences found between youth with well-controlled and inadequately controlled asthma.

Conclusions

Adolescents with asthma are at increased risk of sleep-disordered breathing and suffer from disturbances in sleep continuity with more arousals and sleep fragmentation. Study results highlight the importance of proper screening for sleep-disordered breathing in adolescents with asthma.

http://bit.ly/2DDlT37

Subsidence Fracturing of Stream Channel from Longwall Coal Mining Causing Upwelling Saline Groundwater and Metal-Enriched Contamination of Surface Waterway

Abstract

This study investigated a small waterway that had been impacted by upwelling groundwater due to recent geological strata fracturing caused by subsidence activity from longwall coal mining. Documents from the coal mine report that subsidence has undermined and fractured the stream channel for more than 10 years prior to this study. Mine documents also report many years of variably degraded water quality (salinity, elevated metals) in the reaches affected by fracturing. In this study, water quality of the stream was monitored over an 11-month period with water flow dominated by ground water upwelling through fractures in the creek channel. The upwelling water caused extensive modifications to the creek's surface water quality relative to unmined reference sites. The mean electrical conductivity increased by seven times from 230 μS/cm at reference sites to 1833 μS/cm below the upwelling. Dissolved oxygen in the upwelling groundwater was extremely low (2.7% saturation) and was mildly acidic (5.8 pH). Alterations to the ionic composition included sevenfold increases in magnesium, sodium, and chloride concentrations. Heavy metals iron and manganese increased by more than ten times, with nickel by more than 60 times compared to the reference sites. The alteration to ionic composition was inferred to be saline groundwater intrusion. The ecological impacts of such large modifications to surface stream water quality would be hazardous for integrity of downstream aquatic ecosystems.

http://bit.ly/2RpSNYY

Follow-up blood cultures add little value in the management of bacteremic urinary tract infections

Abstract

The need for mandatory confirmation of negative conversion in bacteremic urinary tract infection (UTI) has not been adequately addressed, even though follow-up blood cultures (FUBCs) are still prescribed liberally. The purpose of this study was to identify possible risk factors associated with positive FUBCs. We retrospectively collected data on adult cases of bacteremic UTI with at least one FUBC. Patients were divided into the negative FUBCs and the positive FUBC group, and data of both groups were compared. Of 306 cases of bacteremic UTI, 251 had a negative result from an FUBC and 55 had a positive result. Diabetes mellitus, malignancy, complicated UTI, and initial intensive care unit (ICU) admission were significantly more common in the positive FUBC group than in the negative group (all-P < 0.05). Time to defervescence was significantly longer in the positive FUBC group than in the negative group (52.2 h vs. 25.3 h, P < 0.05). A multivariate analysis showed that malignancy, initial ICU admission, CRP > 16 (mg/dL), and a time to defervescence of more than 48 h were significant factors associated with a positive FUBC. No subsequent cases of bacteremia developed in patients without risk factors associated with a positive FUBC. In bacteremic UTIs, patients with positive FUBCs usually present with higher initial inflammatory markers, longer time to defervescence, more frequent ICU admission rates, and an elevated chance of having cancer. More careful clinical assessment before drawing FUBCs would reduce costs and inconvenience to patients.

http://bit.ly/2UofZbS

Adverse Cutaneous Drug Reactions Associated with Old- and New- Generation Antiepileptic Drugs Using the Japanese Pharmacovigilance Database

Abstract

Background and Objective

Adverse cutaneous drug reactions associated with antiepileptic drugs (AEDs) are a serious problem in the clinical setting. New-generation AEDs have been reported to be better tolerated than old-generation forms; however, information about the risks of adverse cutaneous drug reactions to new-generation AEDs is limited.

Objective

The purpose of this study was to clarify the association of AEDs with adverse cutaneous drug reactions using a spontaneous reporting database.

Methods

We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between April 2004 and January 2017 were analyzed. Based on reports of all adverse events, we obtained 4805 reports of adverse cutaneous drug reactions associated with AEDs, and calculated the reporting odds ratio (ROR) and 95% confidence interval (CI) for drug rash, Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).

Results

Individual AEDs had variable signals for drug rash, SJS, and TEN. The strongest signals were detected for drug rash caused by lamotrigine (ROR 9.18, 95% CI 8.65–9.74), SJS caused by zonisamide (ROR 9.85, 95% CI 8.23–11.78), and TEN caused by phenobarbital (ROR 14.08, 95% CI 11.28–17.57).

Conclusion

There are clear differences in the risk of cutaneous reactions among AEDs, and further studies are needed to confirm these findings.

http://bit.ly/2FU8kPn

A novel ex vivo trainer for robotic vesicourethral anastomosis

Abstract

Robotic surgical skill development is central to training in urology as well as other surgical disciplines. Vesicourethral anastomosis (VUA) in robotic prostatectomy is a challenging task for novices due to delicate tissue and difficult suturing angles. Commercially available, realistic training models are limited. Here, we describe the development and validation of a 3D-printed model of the VUA for ex vivo training using the da Vinci Surgical System. Models of the bladder and urethra were created using 3D-printing technology based on estimations of average in vivo anatomy. 10 surgical residents without prior robotics training were enrolled in the study: 5 residents received structured virtual reality (VR) training on the da Vinci Skills Simulator ("trained"), while the other 5 did not ("untrained"). 4 faculty robotic surgeons trained in robotic urologic oncology ("experts") were also enrolled. Mean (range) completion percentage was 20% (10–30%), 54% (40–70%), and 96% (85–100%) by the untrained, trained, and expert groups, respectively. Anastomosis integrity was rated as excellent (as opposed to moderate or poor) in 40%, 60%, and 100% of untrained, trained, and expert groups, respectively. Face validity (realism) was rated as 8 of 10 on average by the expert surgeons, each of whom rated the model as a superior training tool to digital VR trainers. Content validity (usefulness) was rated as 10 of 10 by all participants. This is the first reported 3D-printed ex vivo trainer for VUA in robotic prostatectomy validated for use in robotic simulation. The addition of 3D-printed ex vivo training to existing digital simulation technologies may augment and improve robotic surgical education in the future.

http://bit.ly/2G8RhZf

New Insights of Ustilago maydis as Yeast Model for Genetic and Biotechnological Research: A Review

Abstract

The basidiomycete Ustilago maydis is a biotrophic organism responsible for corn smut disease. In recent years, it has become one of the most promising models for biochemical and biotechnological research due to advantages, such as rapid growth, and easy genetic manipulation. In some aspects, this yeast is more similar to complex eukaryotes, such as humans, compared to standard laboratory yeast models. U. maydis can be employed as a tool to explore physiological processes with more versatility than other fungi. Previously, U. maydis was only considered as a phytopathogenic fungus, but different studies have shown its potential as a research model. Therefore, numerous promising studies have focused on deepening our understanding of the natural interactions, enzyme production, and biotechnological capacity. In this review, we explore general characteristics of U. maydis, both as pathogenic and "innocuous" basidiomycete. Additionally, a comparison with other yeast models focusing on genetic, biochemical, and biotechnological research are analyzed, to emphasize the versatility, dynamism, and novelty that U. maydis has as a research model. In this review, we highlight the applications of the yeast form of the fungus; however, since the filamentous form is also of relevance, it is addressed in the present work, as well.

http://bit.ly/2HCZEyk

The relationship between substrate topography and stem cell differentiation in the musculoskeletal system

Abstract

It is well known that biomaterial topography can exert a profound influence on various cellular functions such as migration, polarization, and adhesion. With the development and refinement of manufacturing technology, much research has recently been focused on substrate topography-induced cell differentiation, particularly in the field of tissue engineering. Even without biological and chemical stimuli, the differentiation of stem cells can also be initiated by various biomaterials with different topographic features. However, the underlying mechanisms of this biological phenomenon remain elusive. During the past few decades, many researchers have demonstrated that cells can sense the topography of materials through the assembly and polymerization of membrane proteins. Following the activation of RHO, TGF-b or FAK signaling pathways, cells can be induced into various differentiation states. But these signaling pathways often coincide with canonical mechanical transduction pathways, and no firm conclusion has been reached among researchers in this field on topography-specific signaling pathways. On the other hand, some substrate topographies are reported to have the ability to inhibit differentiation and maintain the 'stemness' of stem cells. In this review, we will summarize the role of topography in musculoskeletal system regeneration and explore possible topography-related signaling pathways involved in cell differentiation.

http://bit.ly/2MBEJdY

The regulatory role of Toll-like receptors after ischemic stroke: neurosteroids as TLR modulators with the focus on TLR2/4

Abstract

Ischemic stroke is the most common cerebrovascular disease and considered as a worldwide leading cause of death. After cerebral ischemia, different pathophysiological processes including neuroinflammation, invasion and aggregation of inflammatory cells and up-regulation of cytokines occur simultaneously. In this respect, Toll-like receptors (TLRs) are the first identified important mediators for the activation of the innate immune system and are widely expressed in glial cells and neurons following brain trauma. TLRs are also able to interact with endogenous and exogenous molecules released during ischemia and can increase tissue damage. Particularly, TLR2 and TLR4 activate different downstream inflammatory signaling pathways. In addition, TLR signaling can alternatively play a role for endogenous neuroprotection. In this review, the gene and protein structures, common genetic polymorphisms of TLR2 and TLR4, TLR-related molecular pathways and their putative role after ischemic stroke are delineated. Furthermore, the relationship between neurosteroids and TLRs as neuroprotective mechanism is highlighted in the context of brain ischemia.

http://bit.ly/2sQBeaw

Bioengineering human vascular networks: trends and directions in endothelial and perivascular cell sources

Abstract

Tissue engineering holds great promise in regenerative medicine. However, the field of tissue engineering faces a myriad of difficulties. A major challenge is the necessity to integrate vascular networks into bioengineered constructs to enable physiological functions including adequate oxygenation, nutrient delivery, and removal of waste products. The last two decades have seen remarkable progress in our collective effort to bioengineer human-specific vascular networks. Studies have included both in vitro and in vivo investigations, and multiple methodologies have found varying degrees of success. What most approaches to bioengineer human vascular networks have in common, however, is the synergistic use of both (1) endothelial cells (ECs)—the cells used to line the lumen of the vascular structures and (2) perivascular cells—usually used to support EC function and provide perivascular stability to the networks. Here, we have highlighted trends in the use of various cellular sources over the last two decades of vascular network bioengineering research. To this end, we comprehensively reviewed all life science and biomedical publications available at the MEDLINE database up to 2018. Emphasis was put on selective studies that definitively used human ECs and were specifically related to bioengineering vascular networks. To facilitate this analysis, all papers were stratified by publication year and then analyzed according to their use of EC and perivascular cell types. This study provides an illustrating discussion on how each alternative source of cells has come to be used in the field. Our intention was to reveal trends and to provide new insights into the trajectory of vascular network bioengineering with regard to cellular sources.

http://bit.ly/2MzX3UI

Induction of apoptosis in ovarian cancer cells by miR-493-3p directly targeting AKT2, STK38L, HMGA2, ETS1 and E2F5

Abstract

Apoptosis is a form of directed programmed cell death with a tightly regulated signalling cascade for the destruction of single cells. MicroRNAs (miRNAs) play an important role as fine tuners in the regulation of apoptotic processes. MiR-493-3p mimic transfection leads to the induction of apoptosis causing the breakdown of mitochondrial membrane potential and the activation of Caspases resulting in the fragmentation of DNA in several ovarian carcinoma cell lines. Ovarian cancer shows with its pronounced heterogeneity a very high death-to-incidence ratio. A target gene analysis for miR-493-3p was performed for the investigation of underlying molecular mechanisms involved in apoptosis signalling pathways. Elevated miR-493-3p levels downregulated the mRNA and protein expression levels of Serine/Threonine Kinase 38 Like (STK38L), High Mobility Group AT-Hook 2 (HMGA2) and AKT Serine/Threonine Kinase 2 (AKT2) by direct binding as demonstrated by luciferase reporter assays. Notably, the protein expression of RAF1 Proto-Oncogene, Serine/Threonine Kinase (RAF1) was almost completely downregulated by miR-493-3p. This interaction, however, was indirect and regulated by STK38L phosphorylation. In addition, RAF1 transcription was diminished as a result of reduced transcription of ETS proto-oncogene 1 (ETS1), another direct target of miR-493-3p. Taken together, our observations have uncovered the apoptosis inducing potential of miR-493-3p through its regulation of multiple target genes participating in the extrinsic and intrinsic apoptosis pathway.

http://bit.ly/2sNLxMB