## Σάββατο, 17 Ιουνίου 2017

### Abstract

The antibiotic doxycycline is used as an inducer of recombinase (cre)-based conditional gene knockout in mice, which is a common tool to show the effect of disrupted gene functions only in one period of a research animal's life. However, other types of such antibiotics have been shown to have a strong impact on the immune system. Here we show that in C57BL/6 mice, the most commonly applied strain for genetic modification, doxycycline treatment lowered transcription of the genes Il1b, Il10, Il18, Tnf, Cxcl1, and Cxcl2 in the ileum, and of the gene Il18 in colon. Cytokines and chemokines encoded by these genes are important in the disease expression in a range of mouse models. Although protein abundances only rarely correlate 100% to transcript levels, and the net result, therefore, may be less dramatic, it seems reasonable to be aware that a broad spectrum antibiotic, such as doxycycline, may impact the transgenic animal in ways unrelated to the activation of the gene deletion.

http://ift.tt/2sFh4lL

### Abstract

Extensive sampling to get rich data is very important to resolve the current taxonomic problem of Chloromyxum genus and elucidate the nature phylogenetic relationships among congeneric species. During the parasitological survey of cyprinid fish in Gulf of Finland off the coast of St. Petersburg, a new Chloromyxum species, named as Chloromyxum peleci sp. n., was found to infect the gall bladder of sichel, Pelecus cultratus (L.). Here, we provided the morphological, ultrastructural, and molecular features to describe it. Infection was represented by mono- or disporic plasmodia and mature free-floating spores in the gall bladder. Mature spores are typical of freshwater Chloromyxum species, spherical or subspherical in lateral view, measuring 8.8 ± 0.5 μm (7.4–9.5) in length, 7.8 ± 0.3 μm (7.0–8.8) in width, and 7.5 ± 0.4 μm (6.8–8.2) in thickness. Spores have a cog-like appearance in apical view for sutural ridge, and eight to ten widely spaced extrasutural ridges per valve protrude from the spore valve margin. The surface ridge patterns of the new species are similar with those of Chloromyxum auratum and Chloromyxum cristatum, with some branching. Four polar capsules of slightly unequal in two pairs were oval in apical view and pyriform in side view, locating at the anterior end of the spores. Polar filaments coil with four to five turns. The obtained almost full length of 18S ribosomal DNA (rDNA) of Ch. peleci sp. n. does not match any sequences available in GenBank but was most closely related to that of Chloromyxum fluviatile (97.9%). Phylogenetic analysis indicated that Ch. peleci sp. n. clustered in a Chloromyxum subclade infecting the gall bladder of freshwater teleost, with robust nodal support. However, Chloromyxum sensu lato infecting gall bladder of freshwater teleost was again proved to be polyphyletic. The possible evolutionary history of Chloromyxum morphotype of Chloromyxum sensu lato was discussed based on the rDNA-referred phylogeny. This is the second Chloromyxum species from sichel.

http://ift.tt/2tAtXd8

### Abstract

The first record of Aedes koreicus was made in the village of Lovrenc na Dravskem Polju, north-eastern part of the country. The discovery of Ae. koreicus in various continental European countries motivated us to revise samples of the collected Aedes japonicus japonicus. We found Ae. koreicus in samples from 2013, where the larvae were misidentified as Ae. j. japonicus. The species was identified morphologically and molecularly. The first discovery of Ae. koreicus advocates an urgent need for a nationwide mosquito surveillance programme.

http://ift.tt/2sCDbrY

### Purpose

The study aims to evaluate the impact of recipients' and donors' polymorphisms in multidrug resistance-associated protein 2 (MRP2) gene ABCC2 -24C>T and 1249G>A on disposition of mycophenolic acid (MPA) and their interaction with cyclosporine (CsA) (compared to tacrolimus, TAC) in stable de novo adult renal transplant patients of Croatian origin.

### Methods

A total of 68 recipient-donor pairs were genotyped. Steady-state pharmacokinetics of MPA was assessed by the model-independent method.

### Results

Adjusted for MPA formulation, renal function, type of calcineurin inhibitor and recipients' and donors' genotypes at the two loci, donors' A-allele at 1249G>A was associated with a reduced peak (29%) and early (AUC0–2, 33%) exposure and increased MPA clearance (26%). Donors' A-allele combined with CsA was associated with 78% higher MPA clearance, 49% lower early and 48% lower total exposure as compared to wild type homozygosity + TAC. Recipients' SNPs per se did not reflect on MPA disposition. However, A-allele at 1249G>A + CsA (compared to wild type + TAC) was associated with a numerically greater increase in MPA clearance (59 vs. 41%), reduction in total exposure (36 vs. 27%) and increase in absorption rate (C max/AUC) (56 vs. 37%) than observed for the main effect of CsA. Less pronounced effects were observed for the combination of variant allele at -24C>T and CsA.

### Conclusion

Considering MPA disposition, data indicate: donors' ABCC2 1249G>A polymorphism increases clearance and reduces exposure; CsA increases clearance and reduces exposure by inhibiting MRP2 in the gut, the liver, and the kidney; donors' ABCC2 1249G>A polymorphism enhances the renal CsA effect, while recipients' polymorphism seems to enhance the liver and the gut CsA effects.

http://ift.tt/2rs1qWv

### Objective

Chemotherapeutic agents have been widely used as adjuncts for the treatment of chronic periodontitis (CP). This study investigated and compared a desiccant agent as an adjunct to scaling and root planing (SRP) versus SRP alone for the treatment of CP.

### Materials and methods

Thirty-six patients with CP were studied. Using a split-mouth design, the maxillary right and left quadrants were randomly assigned to SRP plus desiccant (Hybenx® EPIEN Medical, Inc. St. Paul, MN, USA) or SRP alone. Patients were examined on a regular basis for clinical, microbiological, and inflammatory mediator changes over a 1-year period. Clinical attachment level (CAL) was the primary outcome variable. In addition, the red complex bacteria and gingival crevicular fluid (GCF) inflammatory mediators were monitored.

### Results

Compared to baseline, both treatments demonstrated an improvement in periodontal parameters. Compared to SRP alone, SRP plus desiccant yielded a significant improvement in probing depth (PD) (SRP: 2.23 ± 0.31 mm vs. desiccant: 3.25 ± 0.57 mm, p < 0.05), CAL (SRP: 3.16 ± 0.29 mm vs. desiccant: 4.21 ± 0.34 mm, p < 0.05 mm) and bleeding on probing (BOP) (SRP: 4.56 ± 1.5% vs. desiccant: 34.23 ± 4.2%, p < 0.001) at 12 months. Similarly, in the SRP plus desiccant group, the bacteria of the red complex were significantly reduced (p < 0.05); and the level of inflammatory mediators was significantly reduced (p < 0.003) compared to SRP alone.

### Conclusions

SRP plus the desiccant resulted in a greater reduction in clinical, microbial and inflammatory mediators compared to SRP alone.

### Clinical relevance

Desiccant, when combined to SRP, was demonstrated as a significant approach to control the levels of certain periodontal pathogens, inflammatory mediators in patients with CP.

http://ift.tt/2rrVSey

### Abstract

Understanding the spatial distribution of PM2.5 concentration and its contributing environmental variables is critical to develop strategies of addressing adverse effects of the particulate pollution. In this study, a range of meteorological and land use factors were incorporated into a linear regression (LR) model and a logistic model-based regression (LMR) model to simulate the annual and winter PM2.5 concentrations. The vegetation cover, derived from a linear spectral unmixing analysis (LSUA), and the normalized difference built-up index (NDBI), were found to improve the goodness of fit of the models. The study shows that (1) both the LR and the LMR agree on the predicted spatial patterns of PM2.5 concentration and (2) the goodness of fit is higher for the models established based on the annual PM2.5 concentration than that based on the winter PM2.5. The modeling results show that higher PM2.5 concentration coincided with the major urban area for the annual average but focused on the suburban and rural areas for the winter. The methods introduced in this study can potentially be applied to similar regions in other developing countries.

http://ift.tt/2rDGNe7

### Abstract

Climate change affects water resources worldwide, and Southern Europe is one of the areas where water scarcity is expected to increase in the future. Different water scarcity indicators discussed in this manuscript (e.g. total annual actual renewable water resources, water exploitation index and dependency ratio) showed that some parts of this region are already facing water stress and that climate change could have a great impact on their water supply sector. As agriculture is the biggest consumer of water in the world and also in this particular region, potential water scarcity will impose the need to find new water sources. Treated wastewater reuse would decrease the pressure on the environment and is especially suitable for reuse in agriculture since it already contains some nutrients required for plant growth. However, in order to use it safely, treated wastewater must reach a certain quality that should be regulated. In the south of Europe, 4 countries out of 15 have already adopted wastewater reuse regulations (Greece, Italy, Portugal and Spain). This review compares these regulations and discusses their differences.

http://ift.tt/2snEj0R

### Abstract

The main aim of the study was to evaluate associations between morphological variability of Trichuris females from sheep and roe deer and their rDNA polymorphism in whipworm populations from the Czech Republic. The results introduced the use of new molecular markers based on the internal transcribed spacer (ITS)1-5.8S RNA-ITS2 region polymorphisms, as useful tools for the unambiguous differentiation of congeners Trichuris ovis and Trichuris discolor. These markers revealed both parasites in roe deer and in sheep; however, T. ovis females predominated in sheep while T. discolor females occurred mostly in roe deer. Additional analysis of ITS1-5.8 rRNA-ITS2 discovered the genetic uniformity of the analysed T. discolor but high haplotype variation of T. ovis. Simultaneously, molecularly designated female individuals of both species were categorised into four morphotypes (MT) on the basis of morphology of genital pore area. MT1 and MT4 (vulvar opening on everted vaginal appendage/on visible cuticular bulge) occurred only in T. ovis, MT2 (uneverted vagina—vulvar opening without any elevation) was identified only in T. discolor and MT3 (transient type of vulvar opening on a small swelling) was observed in both species. Statistical analysis of biometric data confirmed that morphology of vulva is not a reliable marker for the species determination. On the basis of the ITS1-5.8S RNA-ITS2 region variability, we carried out a phylogenetic analysis (maximum likelihood method, Hasegawa-Kishino-Yano model) which showed that T. ovis haplotypes from the Czech Republic and Ireland and T. discolor haplotypes from the Czech Republic, Spain, Iran and Japan are sister OTUs.

http://ift.tt/2tA0UX8

### Abstract

Histamine intolerance is a disorder in the homeostasis of histamine due to a reduced intestinal degradation of this amine, mainly caused by a deficiency in the enzyme diamine oxidase (DAO). Among the several multi-faced symptoms associated with histamine intolerance, headache is one of the most recognized and disabling consequences. The aim of this study was to determine the prevalence of DAO deficiency in patients with a confirmed migraine diagnosis according to the current International Headache Society (IHS) and in non-migraine subjects. DAO activity was assessed in a total of 198 volunteers recruited at the Headache Unit of the Hospital General de Catalunya, 137 in the migraine group and 61 as a control group. DAO enzyme activity in blood samples was determined by ELISA test. Values below 80 HDU/ml (Histamine Degrading Unit/ml) were considered as DAO deficient. Mean value of DAO activity from migraine population (64.5 ± 33.5 HDU/ml) was significantly lower (p < 0.0001) than that obtained from healthy volunteers (91.9 ± 44.3 HDU/ml). DAO deficiency was more prevalent in migraine patients than in the control group. A high incidence rate of DAO deficiency (87%) was observed in the group of patients with migraine. On the other hand, 44% of non-migranous subjects had levels of DAO activity lower than 80 HDU/ml. Despite the multifactorial aetiology of migraine, these results seem to indicate that this enzymatic deficit could be related to the onset of migraine.

http://ift.tt/2teQQDE

### Abstract

The proportion of different microbial populations in the human gut is an important factor that in recent years has been linked to obesity and numerous metabolic diseases. Because there are many factors that can affect the composition of human gut microbiota, it is of interest to have information about what is the composition of the gut microbiota in different populations in order to better understand the possibilities for improving nutritional management. A group of 31 volunteers were selected according to established inclusion and exclusion criteria and were asked about their diet history, lifestyle patterns, and adherence to the Southern European Atlantic Diet. Fecal samples were taken and subsequently analyzed by real-time PCR. The results indicated different dietary patterns for subjects who consumed a higher amount of fruits, vegetables, legumes, and fish and a lower amount of bakery foods and precooked foods and snacks compared to Spanish consumption data. Most participants showed intermediate or high adherence to Southern European Atlantic Diet, and an analysis of gut microbiota showed high numbers of total bacteria and Actinobacteria, as well as high amounts of bacteria belonging to the genera Lactobacillus spp. and Bifidobacterium spp. A subsequent statistical comparison also revealed differences in gut microbiota depending on the subject's body weight, age, or degree of adherence to the Southern European Atlantic Diet.

http://ift.tt/2sF7oHS

### Abstract

A novel Gram-positive, aerobe, moderately halophilic bacterium was isolated from saline soil of Aiding lake in Xinjiang, north-west of China, designated strain YIM 98001T. Cells were rod-shaped, motile and grew at 5–20% (w/v) NaCl (optimum 10%), pH 6–10 (optimum pH 7.0) and 4–45 °C (optimum 37 °C). The major cellular fatty acids were anteiso C15:0, anteiso C17:0, iso C15:0. The predominant respiratory quinone was MK-7. Diphosphatidylglycerol, phosphatidylglycerol, phosphoglycolipid were the major polar lipids. Meso-diaminopimelic acid was the diagnostic diamino acid of the cell-wall peptidoglycan. The G+C content was 36.46 mol%. 16S rRNA gene sequence analysis showed that the strain belongs to the family Bacillaceae, with the highest sequence similarity to the type strain Gracilibacillus thailandensis TP2-8T (96.84%), followed by Gracilibacillus saliphilus YIM 91119T (96.78%) and Gracilibacillus ureilyticus MF38T (96.57%), thus confirming the affiliation of strain YIM 98001T to the genus Gracilibacillus. The polyphasic approach indicates that strain YIM 98001T represents a novel species of the genus Gracilibacillus, for which the name Gracilibacillus aidingensis is proposed. The type strain is YIM 98001T (=KCTC 42683T = DSMZ 104330T).

http://ift.tt/2sn3rET

### Purpose

The purpose of this study is to determine the rate of QTcP and associated risk factors in patients treated with voriconazole.

### Methods

We conducted a retrospective chart review of all patients treated with voriconazole in a large tertiary center between 2009 and 2015, using paired comparison of QTc intervals on and off voriconazole treatment, adjusted for comorbidities, electrolyte abnormalities, and concurrent medications.

### Results

Fifty-four patients were included, of whom 53 were diagnosed with oncologic/hemato-oncologic disease. Mean QTc during voriconazole therapy (448.0 ± 52.9 msec) was significantly longer compared to QTc off voriconazole (421.8 ± 42.2 msec; p = 0.002). QTcP ≥30 msec and ≥60 msec was demonstrated in 43% (23 patients) and 28% (15 patients), respectively. Multivariate analysis showed that QTcP was significantly associated with baseline QTc ≥ 450 msec (upper QTc quartile) (p < 0.01) and low serum potassium levels (p < 0.01). Contrarily, no significant association was found between mean voriconazole daily and cumulative dose and QTcP.

### Conclusion

Our findings indicate that hemato-oncologic patients treated with voriconazole are at increased risk for QTcP, especially in the presence of baseline QTc ≥ 450 msec and low serum potassium levels.

http://ift.tt/2sKaXw0

### Abstract

The genus Anableps is composed of species Anableps anableps, Anableps dowi, and Anableps microlepis. These fishes are tropical and usually live on the surface of brackish water, being popularly known as four-eyed-fishes due to the presence of prominent eyes and a pupil split horizontally. A. anableps and A. microlepis are considered as sister species that live in sympatry in South America. A. dowi, however, is restricted to the Pacific Ocean (Central America) and is considered the most primitive species of this genus. The aims of this study were to investigate the presence of endoparasites in A. anableps from the Parnaíba's Delta and characterize them morphologically. During the necropsy, larvae of Contracaecum sp. in the third larval stage (L3) were collected from the pancreas of A. anableps, but no endoparasites were observed in other organs. The worms had a cuticular tooth and excretory pore located at the anterior end, a thread like body, whitish color, and without distinction of sex. The length of the ventricular appendix of the larvae was much greater than in other studies. This is the first report of endoparasitism in A. anableps and the first report of nematodes in four-eyed-fishes.

http://ift.tt/2sBol5i

### Abstract

Primary cilia are solitary, microtubule-based protrusions of the cell surface that play fundamental roles as photosensors, mechanosensors and biochemical sensors. Primary cilia dysfunction results in a long list of developmental and degenerative disorders that combine to give rise to a large spectrum of human diseases affecting almost any major body organ. Depending on the cell type, primary ciliogenesis is initiated intracellularly, as in fibroblasts, or at the cell surface, as in renal polarized epithelial cells. In this review, we have focused on the routes of primary ciliogenesis placing particular emphasis on the recently described pathway in renal polarized epithelial cells by which the midbody remnant resulting from a previous cell division event enables the centrosome for initiation of primary cilium assembly. The protein machinery implicated in primary cilium formation in epithelial cells, including the machinery best known for its involvement in establishing cell polarity and polarized membrane trafficking, is also discussed.

http://ift.tt/2rCXu9L

### Purpose

Paracetamol overdose is common and is treated with acetylcysteine to prevent the development of hepatotoxicity. N-acetyl-p-benzoquinone imine (NAPQI) is the toxic metabolite of paracetamol overdose. We aimed to assess the expected acetylcysteine concentration time profiles following delivery of modified acetylcysteine regimens proposed for those at high and low risk of hepatotoxicity. In addition, we will determine acetylcysteine concentrations post-cessation of abbreviated infusions.

### Method

We performed pharmacokinetic simulations using Berkeley Madonna (version 8.3.23.0) comparing the time course of acetylcysteine concentration during and after the cessation of an abbreviated 12-h regimen (250 mg/kg) using a two-bag infusion and compared this to the standard 21-h three-bag (300 mg/kg) regimen. We also simulated extended duration acetylcysteine regimens and other increased dosing strategies that have been recommended in specific paracetamol poisoning scenarios.

### Results

A more sustained serum concentration is achieved when the acetylcysteine loading dose is delivered over 4 h using the two-bag compared to the 1-h loading dose of the three-bag regimen. When administering an abbreviated 12-h acetylcysteine regimen, circulating acetylcysteine is detectable for 8 h after cessation of the infusion. This may provide a continued hepatoprotective effect if NAPQI is still being generated after the infusion is ceased.

### Conclusion

This pharmacokinetic simulation study is an important step in determining plasma acetylcysteine concentrations that are likely to be achieved using various modified treatment regimens. Importantly, for patients at low risk of liver injury after acute overdose, acetylcysteine is likely to be detectable many hours post-cessation of a 12-h regimen. This should provide a safety factor against development of hepatotoxicity for any ongoing paracetamol metabolism after cessation of the acetylcysteine infusion.

http://ift.tt/2tz8WPU

### Abstract

Testicular development and spermatogenesis are strictly regulated with the complex interactions between several cell types in testis. However, the limited availability of genomic and molecular information limits our understanding of this complex physiological process. In this study, we characterized the transcriptome between immature (30-day-old) and mature (180-day-old) pig testes using RNA-seq technology. 24,469 known coding gene transcripts corresponding to 20,566 genes were mapped in these two developmental stages, 3,328 genes were differentially expressed, and numerous novel transcripts and alternative splicing events were also identified. Ten differentially expressed genes were validated by measuring the relative expression using real-time quantitative polymerase chain reaction (PCR). 125 Gene Ontology (GO) terms were significantly enriched, and most of them involved in GO terms related to male reproduction, testicular development, and spermatogenesis. In addition, this study also represented the prediction of 10,000 circRNAs, as well as the validation of six pig circRNAs using Find_cric algorithm. Our study substantially expanded our knowledge about the transcriptomic profile of immature and mature pig testes, and provided a useful resource to study the mechanisms of pig testis development and spermatogenesis at the molecular level.

http://ift.tt/2smGfGH

### Abstract

Zinc finger protein 703 (ZNF703) is a putative oncogene in patients with the luminal B molecular subtype of breast cancer. Although the exact function of ZNF703 protein remains largely unknown, its expression and regulation have been implicated in several physiological and pathological processes. In the current study, for the first time, we identified and characterized the human ZNF703 gene promoter region. As a means of characterizing the transcription elements required for expression of ZNF703 protein at different stages, we cloned the promoter region of ZNF703 then created chimeric reporter plasmids for use in luciferase assays. A progressive deletion analysis of the ZNF703 gene's 5′ and 3′ -flanking regions revealed that the core promoter is located in a 256-bp region ranging from nt-539 to nt-283. Next, we examined the effects of site-specific mutations and treatment with mithramycin A to identify the functional Sp1 binding site, which was found to be located in a 447 bp region that ranged from nt-509 to nt-76, displayed the characteristics of a CpG island, and overlapped with the promoter region. In conclusion, our data suggest that ZNF703 transcription is regulated by transcription factor Sp1. This finding should facilitate future studies of the mechanism which regulates expression of this important gene.

http://ift.tt/2sK32Px

### Abstract

Linalool, α-terpineol, citronellol, nerol, geraniol, and geraniol acid are the main monoterpenes in the grapevine (Vitis vinifera L.) with the concentrations of these substances differing in different varieties. This research performed association analyses using a core collection of 92 grape accessions to identify causal SNPs in the gene 1-deoxy-d-xylulose-5-phosphate synthase (VvDXS), a regulator of monoterpene metabolism. We evaluated the free linalool, α-terpineol, citronellol, nerol, geraniol, and geraniol acid content of 92 grape varieties in two consecutive years (2014 and 2015). Twenty-two SNPs were found in the VvDXS coding region and were used in an association analysis. We found that the linalool, α-terpineol, nerol, and geraniol acid levels were higher in varieties with a G/T genotype at P852 than in varieties with other genotypes at this site. Additionally, we found a novel polymorphism site P1678 (A/G) with a functional effect on terpenoid content that was related to the regulation of gene transcription. This study revealed the relationship between VvDXS and aroma, with the identified polymorphism site potentially assisting in the screening of aroma compounds at early stages in fruit development in grapevines.

http://ift.tt/2rCy5N6

### Abstract

Endogenous retrovirus (ERV) integrates into the germline of its host and could remain in the genome as a molecular fossil. ERV is one of sources that cause INDEL and recombination events in the vertebrate genomes, leading to various genomic and genetic changes in their hosts. There have been many studies conducted on ERVs in the vertebrate genomes to elucidate their evolutionary history. However, ERVs have not been studied well in Crocodylus siamensis. Here, we report structural variations among SFV1 elements (simian foamy virus-like), ERVs in C. siamensis. We initially identified 26 SFV1 candidates in the genome and experimentally verified 9 SFV1_1 and 5 SFV1_10 elements using PCR display. Their structural analyses showed that most of them are solitary-LTRs but two SFV1_1 elements are full-length. Through further analyses, we found that the two full-length elements retain intact ORFs. We examined transcription factor binding sites within their LTR sequences to predict promoter/enhancer activities. In sum, we identified 14 crocodile-specific SFV1 elements and the results of their structural analyses suggest that they could contribute to genomic or phenotypic variations in C. siamensis population.

http://ift.tt/2smL0Ae

### Abstract

The surgical indications of zygomatic fracture include aesthetic and functional impairment. No standard method exists for assessing the functional outcome nowadays, and traditional methods are subjective and inadequately quantitative for comprehensive analyses. This study was conducted to obtain a clinically applicable, reliable, quantitative, and noninvasive system for measuring the jaw function through kinematic, kinetic, and surface electromyography (sEMG) analysis. Because we previously established a model based on a healthy population, we applied the proposed system to patients with zygomatic fracture for this study. The study group comprised 20 young adults (18 male, 2 female) with simple zygomatic fracture. Twelve of them received open reduction and plate fixation (surgical group) and the other eight did not (nonsurgical group). We used a jaw motion analyzer to detect jaw movement, a sEMG instrument to evaluate the activity of the bilateral temporalis and masseter muscle, and an occlusal bite force system to measure the bite force. We compared jaw function over the affected side and sound side, and among the surgical group, nonsurgical group, and healthy population. In the surgical group, no functional difference was observed over the affected side and sound side 2 months after operation. However, the sEMG analysis revealed that the temporalis and masseter muscle and bite force exhibited less function over the affected side than over the sound side 3 months after the injury occurred in non-surgical group. Compared with the healthy population, the surgical group exhibited a shorter condylar path, narrower maximal mouth opening, less sEMG activity over masseter muscle, and less bite force over the affected side at 1 month after operation; however, their condition improved and did not differ from the control group at 2 months after operation. By contrast, the nonsurgical group continued to exhibit poorer jaw movement, less sEMG activity, and less bite force compared with the healthy population even 3 months after injury. Furthermore, the bite force was significantly lower in the nonsurgical group than in the surgical group at post-operative 3 month. (p = .002). We obtained a clinically applicable, quantitative, reliable, and noninvasive system for evaluating jaw and mastication function with biofeedback characteristics. For patients with a simple zygomatic fracture, the degree of jaw movement, sEMG activity, and bite force could return to normal by the second month after open reduction, stable fixation, and early rehabilitation.

http://ift.tt/2sB9IPm

### Abstract

An increasing number of patients are being treated with cardiovascular implantable electronic devices (CIEDs), many of which are MR conditional. There is a lack of literature on the safe scanning of MR conditional CIEDs. This review article discusses MR imaging safety in patients with implanted CIEDs. Guidelines on safe use and indications of imaging patients with MR conditional CIEDs are described, followed by a pictorial essay of the radiographic features of these devices. We also discuss the challenges of monitoring the patient in the MR environment, advances in MRI conditional imaging of devices, availability, limitations and workflow including vendor-specific and other collaborative efforts to simplify the scanning process. Radiologists must be able to facilitate the safe utilization of MR imaging in patients who have CIEDs. A thorough knowledge of the hazards of imaging non-MR compatible devices is required as well as knowing how to correctly identify and manage the imaging of patients with MR conditional CIEDs. Finally, we propose steps required to facilitate the safe scanning of patients with MR conditional CIEDs adopted in our institution and a contingency plan in the event that an inadvertent MR scan of a patient with a MRI unsafe CIED should occur.

### Main Messages

Risks of MR imaging in patients who have CIEDs have been worked around.

There are many technical limitations in enabling safe MR scanning of CIEDs.

Radiological identification of MRI-conditional status of CIEDs is useful.

Standardizing conditions for safe MRI scanning is important.

We offer example algorithms for facilitating safe MRI scanning of CIEDs.

http://ift.tt/2rqTHYL

### Abstract

The aim of this work was to investigate the possibility of covalent cross-linker-free, polyelectrolyte complex formation at the nanoscale between alginic acid (as sodium alginate, ALG) and protamine (PROT). Optimisation of the self-assembly conditions was performed by varying the type of polymer used, pH of component solutions, mass mixing ratio of the components and the speed and order of component addition on the properties of complexes. Homogenous particles with nanometric sizes resulted when an aqueous dispersion of ALG was rapidly mixed with a solution of PROT. The polyelectrolyte complex between ALG and PROT was confirmed by infrared spectroscopy. To facilitate incorporation of drugs soluble at low pH, pH of ALG dispersion was decreased to 2; however, no nanoparticles (NPs) were formed upon complexation with PROT. Adjusting pH of PROT solution to 3 resulted in the formation of cationic or anionic NPs with a size range 70–300 nm. Colloidal stability of selected alginic acid low/PROT formulations was determined upon storage at room temperature and in liquid media at various pH. Physical stability of NPs correlated with the initial surface charge of particles and was time- and pH-dependent. Generally, better stability was observed for anionic NPs stored as native dispersions and in liquids covering a range of pH.

Schematic presenting the formation and size of alginate/protamine nanoparticles

http://ift.tt/2smIeL8

### Abstract

Radiofrequency (RF) coils are key components in magnetic resonance (MR) systems since the use of coils which fit around parts of the body to be imaged is necessary for obtaining high-quality images. As a first approximation, an RF coil is essentially a tuned electrical circuit that comprises an inductor and a capacitor, which may be adjusted to make the resonant frequency the desired Larmor frequency. Capacitor losses can drastically reduce RF coil overall performances. This work reviews literature describing how the choice of the capacitors quality affects the coil overall performance. Moreover, experiments with a loop-conductor coil were performed comparing low and high-quality capacitors with benchtop tests at high and low frequencies, and an imaging test was performed with a 1.5 T MR clinical scanner.

http://ift.tt/2smE3PH

### Abstract

Early embryos of the clitellate annelid Tubifex (oligochaete) undergo a series of unequal spiral cell divisions before the descendants of the D quadrant micromeres (cells 2d and 4d) divide bilaterally. Here, we show that inhibition of zygotic transcription by microinjection of α-amanitin (transcription inhibitor) exclusively converts unequal cleavage in cell 2d11 (granddaughter of 2d) into equal cleavage while other unequal cleavages and ensuing bilateral cleavages in cells 4d and 2d111 (great-granddaughter of 2d) all proceed in a normal fashion in the presence of this inhibitor. These results differ significantly from those reported for embryos of another clitellate annelid Helobdella (leech), in which inhibition of transcription converts bilateral (symmetric) cleavages in cells DNOPQ"' and DM" (equivalent to 2d111 and 4d) into unequal (asymmetric) cleavages while having no apparent effect on unequal cleavage in DNOPQ" (equivalent to 2d11). These differences imply distinct mechanisms for the control of the unequal-to-bilateral transition in the two clitellate annelids.

http://ift.tt/2sciv9Y

### Abstract

In orthodontic treatment with fixed appliances, the use of nickel alloy for archwire may cause nickel allergy suffered from the release of nickel ions. In addition, esthetic concerns are a problem for many people. Shape memory polymer (SMP), as a functional material with the ability of thermo-driven shape change to produce force and with good biocompatible properties, possesses the potential to be used in orthodontic appliances. To investigate the feasibility of using polyurethane (PU) as orthodontic archwire, a kind of SMP, namely shape memory polyurethane (SMPU), a simulation via finite element method was conducted, based on a new three dimensional (3D) thermo-mechanical constitutive model and data acquired from some mechanics experiments related to temperature. Finally, a tooth-moving simulation with SMPU archwire on a wax model was performed. The results illustrated that SMPU wire shows good prospects in orthodontic application: the archwire with a 0.5 mm diameter can supply recovery force with magnitude 0.588–1.176 N (60–120 g), which is within the required range 0.49–2.94 N (50–300 g) for tooth movement. However, the force is smaller than that produced from metal wire, and more work related to material strengthening, such as filling SMPU with reinforcement material, is required in the future.

http://ift.tt/2rCp1rE

### Abstract

Accurate measurement of bone position in vivo during dynamic activities has the potential to improve our identification and understanding of injury mechanisms and enhance our ability to design protective equipment and/or devices for rehabilitation and human augmentation. Existing technologies such as skin-mounted reflective markers and fluoroscopy are limited either in accuracy or portability. The purpose of this study was to demonstrate a proof of concept for an ultrasound (US) sensor array to measure bone positions around a human joint in vivo. A single off-the-shelf US sensor was tested for repeatability and accuracy in measuring soft tissue depth between the skin surface and embedded bone with (a) a gelatinous analog for human tissue, and (b) a porcine leg specimen. In measuring the hydrogel analog the sensor was able to measure depth with a repeatability of 0.25 mm. In measuring the porcine leg specimen, measurement accuracy was compared to a Qualisys optical motion capture system with accuracy on the order of 0.5 mm, and the US measurement uncertainty was found to be 1.1 mm. An additional set of tests on a similar system performed on a human participant performing elbow flexion/extension confirms that the method is usable for evaluating both the bone position and the muscle volume during movement analysis measurements. This study demonstrates that low cost off-the-shelf US sensors have acceptable quality to measure bone positions accurately in vivo.

http://ift.tt/2smgy9p

### Abstract

The present study aimed to investigate second language (L2) word-level and sentence-level automatic processing among English as a foreign language students through a comparative analysis of students with different proficiency levels. As a multidimensional and dynamic construct, automaticity is conceptualized as processing speed, stability, and accuracy which are indexed by reaction time, coefficient variation and accuracy rate. Sixty students (39 undergraduate students and 21 graduate students) who majored in English participated in this study. They completed the lexical semantic classification task, the sentence construction task, the sentence verification task under two different modalities (visually- and aurally-presented situations). Multivariate analyses were conducted to examine the differences between the students with different proficiency levels pertaining to their L2 performance. The results indicated that the processing speed was not found to be a good indicator of automatic language processing. Moreover, both levels of students appeared to reach a plateau in word-level processing but there were some variations in students' sentential processing. Finally, the findings showed that automatic language processing seemed to be module-specific and non-sharable across different modalities and skills.

http://ift.tt/2tyOHC2

### Background

For some stroke patients and caregivers, navigating the transition between hospital discharge and returning home is associated with substantial psychosocial and health-related challenges. Currently, no evidence-based standard of care exists that addresses the concerns of stroke patients and caregivers during the transition period. Objectives of the Michigan Stroke Transitions Trial (MISTT) are to test the impact of a social worker home-based case management program, as well as an online information and support resource, on patient and caregiver outcomes after returning home.

### Methods

The Michigan Stroke Transitions Trial is a randomized, pragmatic, open (un-blinded), 3-group parallel designed superiority trial conducted in 3 Michigan hospitals. Eligible participants are adult acute stroke patients discharged home directly or within 4 weeks of being discharged to a rehabilitation facility. The patient's primary caregiver is also invited to participate. Patients are randomized on the day they return home using a randomized block design. Consented patients discharged to a rehabilitation facility who do not go home within 4 weeks are dropped from the study.

The 2 study interventions begin within a week of returning home and conclude 3 months later. The 3-group design compares usual care to either a home-based social worker stroke case management (SWSCM) program, or a combination of the SWSCM program plus access to an online information and support resource (MISTT website). Outcomes data are collected at 7-days and 90-days by trained telephone interviewers. Primary patient outcomes include the PROMIS global 10 score (a generic Quality of Life scale), and the Patient Activation Measure (PAM). Caregiver outcomes include the Bakas Caregiving Outcomes Scale. Final analysis will be based on 214 randomized acute stroke patients. To accommodate subjects excluded due to prolonged rehabilitation stays, as well as those lost-to-follow-up, up to 315 patients will be consented.

### Discussion

The MISTT study will determine if a home-based case management program designed around the needs and preferences of stroke patients and caregivers, alone or in combination with a patient-centered online information and support resource can improve stroke survivor and caregiver outcomes 3 months after returning home.

### Trial registration

ClinicalTrials.gov: NCT02653170 (Protocol ID: 135457). Registered April 9, 2015.

http://ift.tt/2rGNebG

### Background

Epilepsy is a serious and costly long-term condition that negatively affects quality of life, especially if seizures persist on medication. Studies show that people with epilepsy (PWE) want to learn more about the condition and some educational self-management courses have been trialled internationally. The objectives of this review were to evaluate research and summarise results on group self-management interventions for PWE.

### Methods

We searched Medline and PsycINFO for results published in English between 1995 and 2015. Only studies evaluating face-to-face, group interventions for adults with epilepsy were included. Heterogeneity in study outcomes prevented the carrying out of a meta-analysis; however, a Cochrane style review was undertaken.

### Results

We found eleven studies, nine of which were randomised controlled trials. There were variable standards of methodological reporting with some risk of bias. Seven of the studies used quality of life as an outcome, with four finding statistically significant improvements in mean total score. Two found an improvement in outcome subscales. One study included some additional semi-qualitative data.

### Conclusions

We identified promising trends in the trials reviewed. In particular, there were significant improvements in quality of life scales and seizure frequency in many of the interventions. However, considerable heterogeneity of interventions and outcomes made comparison between the studies difficult. Courses that included psychological interventions and others that had a high number of sessions showed more effect than short educational courses. Furthermore, the evidence was predominantly from pilot studies with small sample sizes and short follow-up duration. Further research is needed to better evaluate the role of group self-management interventions in outpatient epilepsy management.

http://ift.tt/2rGRmIo

### Abstract

http://ift.tt/2rqIEid

### Abstract

Since their 're-discovery' more than two decades ago, FOXP3+ regulatory T cells (Tregs) have been an important subject of investigation in the biomedical field and our understanding of the mechanisms that drive their phenotype and function in health and disease has advanced tremendously. During the past few years it has become clear that Tregs are not a terminally differentiated population but show some degree of plasticity, and can, under specific environmental conditions, acquire the phenotype of effector T cells. In particular, recent works have highlighted the acquisition of a Th1-like phenotype by Tregs in several pathological environments. In this review we give an update on the concept of Treg plasticity and the advances in defining the molecular mechanisms that underlie the generation of Th1-like Tregs during an immune response and in different disease settings.

http://ift.tt/2tdrJRs

### Abstract

Unsaturated fatty acid biohydrogenation products from beef fat and pure fatty acids were subjected to the Ames Salmonella mutagenicity testing, including monounsaturated fatty acids [MUFA: oleic acid, vaccenic acid, elaidic acid; beef fatty acid fractions rich in trans (t)11/t13-t14-18:1 (t11,13,14-Frac), t10-18:1 (t10-Frac)] and dienoic fatty acids [linoleic acid, conjugated linoleic isomers cis (c)9,t11-18:2 and t10,c12-18:2, and a mixed beef dienoic fatty acid fraction high in c9,t13-/t8,c12/t11c15-18:2 (MD)]. Significantly higher anti-mutagenic effects of oleic acid, vaccenic acid, t11, 13, 14-Frac, and t10-Frac against daunomycin were observed at 2.5 mg. All dienoic acids except MD significantly reduced daunomycin mutagenicity at ≥0.25 mg. Anti-mutagenicity of oleic and vaccenic acids against 2-aminoanthracene was found at 2.5 and 0.25 mg, respectively. All dienoic acids significantly reduced 2-aminoanthracene mutagenicity at ≥0.25 mg. Findings of this study show that unsaturated fatty acids, including trans-fatty acids commonly found in beef, can act as strong anti-mutagens.

http://ift.tt/2rC0C5t

### Abstract

Studying sleeping behavior can provide key information for understanding the ecology of a species. Antipredation is an important factor that affects primate sleeping behavior. We studied antipredation sleeping behavior in skywalker hoolock gibbons (Hoolock tianxing). We studied one group (NA) and a solitary female (NB) at Nankang from July 2010 to September 2011, and another group (BB) at Banchang from May 2013 to December 2014 in Mt. Gaoligong, Yunnan, China. Over the study period, we recorded 67 sleeping trees for members of group NA over 92 days, 17 trees for the solitary female NB over 22 days, and 159 trees for members of group BB over 186 days. Skywalker hoolock gibbons at both sites rarely used the same tree on consecutive days (N = 3 at both sites). They traveled fast to enter sleeping tree a mean of 160 ± SD 43 min before sunset at Nankang, and a mean of 192 ± SD 40 min before sunset at Banchang. They seldom (Nankang: 14%, N = 183 observations; Banchang: 25%, N = 548 observations) defecated in sleeping trees. They slept at sites with more tall and large trees and preferred to sleep on tall trees in the site. They slept on branches of small diameter and closer to tree tops. Our study suggests that antipredation plays an important role in skywalker hoolock gibbons' sleeping tree selection and sleeping behavior. In addition, our data suggest potential effects of habitat degradation on gibbons' sleeping behavior. Tall trees are especially important for gibbons in degraded forest and should be protected.

http://ift.tt/2slydxS

### Abstract

One of the important questions when studying established cancer cell lines is whether such cells contain a subpopulation of primitive cancer stem cells that maintains the expansion of the cell line. To address this issue, we performed studies on the established human embryonal carcinoma cell line NTera2 by evaluating the potential stemness of cells sorted according to their expression of the cell surface stem cell markers CD133 and SSEA4. By performing in vitro and in vivo assays, we observed different properties of cells expressing both, one, or neither of these antigens. While sorted SSEA4+ subpopulations exhibited the greatest propensity for migration toward normal serum and the highest seeding efficiency in the lungs of immunodeficient mice, CD133SSEA4 cells displayed high seeding efficiency to the bone marrow after injection in vivo. It is worth noting that these properties did not depend on the size of the evaluated cells. To address the question of whether cancer stem cell phenotypes in cell lines are fixed or fluctuating, we sorted single cells according to their expression of CD133 and SSEA4 antigens and observed that cells which did not express these cancer stem cell markers gave rise to cells that express these markers after expansion in vitro. Therefore, our results support the idea that within established cancer cell lines, the phenotype of the cell subpopulation expressing cancer stem cell markers is not fixed but fluctuates during cell line expansion, and cells negative for these markers may acquire their expression.

http://ift.tt/2tdilxd

### Abstract

Abaloparatide (Tymlos™) is a synthetic peptide analogue of human parathyroid hormone-related protein that was developed by Radius Health as an osteoanabolic agent for the treatment of postmenopausal osteoporosis. Abaloparatide acts through selective activation of the parathyroid hormone type 1 receptor signalling pathway. In April 2017, subcutaneous abaloparatide received its first global approval, in the USA, for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. A Marketing Authorization Application for subcutaneous abaloparatide for the treatment of postmenopausal women with osteoporosis was accepted by the European Medicines Agency and is currently under review. Radius is also developing a transdermal formulation of abaloparatide, with administration via a microneedle patch. This article summarizes the milestones in the development of abaloparatide leading to this first approval for the treatment of women with postmenopausal osteoporosis.

http://ift.tt/2td44kr

### Abstract

The mechanical properties of arteries play an essential role in the study of the circulatory system dynamics, which has been becoming increasingly important in the treatment of cardiovascular diseases. Similarly, when building virtual reality simulators, it is crucial to have a tissue model able to respond in real time. The aim of this work is to linearize an artery model to calculate the stiffness of springs. Arteries with three tissue layers (Intima, Media, and Adventitia) are considered and, starting from the stretch-energy density, some of the elasticity tensor components are calculated. The artery is discretized by a two dimensional mesh where the nodes are connected by three kinds of linear springs (one normal and two angular ones). The model linearizes and homogenizes the material response, but it still contemplates the geometric nonlinearity. Comparisons showed a good match with a nonlinear model and with a standard two-dimensional finite element model, when the artery undergoes a stretch in the circumferential and axial directions. The agreement is also good if the arterial tissue undergoes bending. Finally, the Intima layer shows the biggest deviation from linearity when there is a large deformation in the axial direction. If the arterial stretch varies by 1% or less, then the agreement between the linear and nonlinear models is trustworthy.

http://ift.tt/2rBZe30

### Background and objectives

Ultra-long-acting insulin degludec (DEG) has a longer duration of action and less daily variability relative to other basal insulin (BI), and thus may benefit patients with type 1 diabetes mellitus (T1DM). We examined the impact of switching BI to DEG on glycemic control and insulin dose in T1DM.

### Methods

T1DM patients (n = 22; six male; mean age: 64.5 ± 12.6 years) receiving basal-bolus insulin therapy were included. Initially, the BI dose was replaced with DEG in a 1:1 ratio; 80–100% of the total dose was replaced with DEG for multiple basal insulin injections. DEG was titrated according to study protocol. Changes in HbA1c, daily insulin dose, glycemic self-monitored blood glucose variations, and hypoglycemia frequency were evaluated for 24 weeks.

### Results

Once-daily DEG significantly decreased HbA1c levels when switched from once-daily BI (7.9 ± 0.8 vs. 7.5 ± 0.9%, p = 0.020) and maintained HbA1c when switched from twice-daily BI (8.5 ± 1.6 vs. 8.4 ± 1.2%, p = 0.457). The BI dose decreased by −7.8 ± 13.9% (p = 0.017) and −16.6 ± 16.9% (p = 0.050) when switched from once-daily BI and twice-daily BI, respectively. The total bolus insulin dose significantly decreased when switched from once-daily BI (21.7 ± 8.3 to 19.3 ± 8.8 U/day, p = 0.016) especially in the injection before breakfast and evening meal. Body weight and hypoglycemia frequency was not significantly different.

### Conclusion

DEG improved glycemic control when switched from once-daily BI and maintained glycemic control when switched from twice-daily BI without increasing hypoglycemia.

http://ift.tt/2rC0SSe

### Background

Aggressive natural killer cell leukemia/lymphoma (ANKL) is a rare and highly aggressive NK cell neoplasm with a short clinical course and poor prognosis and is often misdiagnosed and confused with NK/T cell lymphoma (NKTL), which has a very different prognosis. Here, we present a case with nasal and bone marrow involvement, provide a literature review and make a differential diagnosis.

### Case presentation

A 41-year-old male presented nasal congestion pharyngalgia, palatal perforation, high fever and multiorgan dysfunction. Our diagnosis primarily relied on clinical features, the morphology and immunophenotype of the neoplastic cells and imaging studies. Characteristic large granular lymphocytes with azurophilic granules were visible in the bone marrow smears. In addition, the neoplastic cells expressed a typical immunophenotype, and the T cell receptor γ (TCR-γ) gene rearrangement analysis and presence of Epstein-Barr virus (EBV) were negative. The patient's symptoms and signs were temporarily relieved after chemotherapy treatment, but after a short time, he underwent a rapid clinical decline and died 8 weeks later after admission due to multiorgan function failure.

### Conclusion

Our case demonstrates that to avoid a misdiagnosis, bone marrow analyses and other examinations should be performed early when a patient initially presents nasal lesions and other systemic symptoms. To the best of our knowledge, this may be the first reported case of ANKL with sternal tenderness.

http://ift.tt/2sArhPC

### Background

The programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) immune regulatory axis has emerged as a promising new target for cancer therapeutics, with lasting responses seen in the treatment of metastatic renal and lung carcinomas, as well as melanomas. As tumor surface expression of PD-L1 has been found to correlate with objective responses to anti-PD-L1 immunotherapies, we investigated the expression of PD-L1 in human cervical tumors and provide an adopted scoring system for the systematic evaluation of PD-L1 staining.

### Methods

Immunohistochemical staining for PD-L1 expression was performed on a tissue microarray of 101 normal and neoplastic cervical tissues. Neoplastic cores were divided into three groups: squamous cell carcinoma, adenosquamous carcinoma, and endocervical adenocarcinoma. PD-L1 expression was scored based on an adopted scoring system accounting to percentage and intensity of positivity, and results provided alongside available clinical and demographic data.

### Results

Overall, PD-L1 was positive in 32 of 93 (34.4%) cervical carcinomas. Subcategorically, PD-L1 was positive in 28 of 74 (37.8%) squamous cell carcinomas, two of seven (28.6%) adenosquamous carcinomas, and two of 12 (16.7%) endocervical adenocarcinomas. It was negative in six benign cervical tissues.

### Conclusions

This study shows a significant expression of PD-L1 in 34.4% of cervical carcinomas and no expression of PD-L1 in benign cervical tissues. These findings suggest a role for further investigation of anti-PD-L1/PD-1 immunotherapies in the treatment of PD-L1-positive cervical tumors. In addition, our adopted scoring system will facilitate more systematic correlations between tumor reactivity and response to treatment.

http://ift.tt/2ty4dhp

### Abstract

A wide range of studies on language assessment during awake brain surgery is nowadays available. Yet, a consensus on a standardized protocol for intraoperative language mapping is still lacking. More specifically, very limited information is offered about intraoperative assessment of a crucial component of language such as syntax. This review aims at critically analyzing the intraoperative studies investigating the cerebral basis of syntactic processing. A comprehensive query was performed on the literature, returning a total of 18 studies. These papers were analyzed according to two complementary criteria, based on the distinction between morphosyntax and syntax. The first criterion focused on the tasks and stimuli employed intraoperatively. Studies were divided into three different groups: group 1 included those studies that overtly aimed at investigating morphosyntactic processes; group 2 included studies that did not explicitly focus on syntax, yet employed stimuli requiring morphosyntactic processing; and group 3 included studies reporting some generic form of syntactic deficit, although not further investigated. The second criterion focused on the syntactic structures of the sentences assessed intraoperatively, analyzing the canonicity of sentence structure (i.e., canonical versus non-canonical word order). The global picture emerging from our analysis indicates that what was investigated in the intraoperative literature is morphosyntactic processing, rather than pure syntax. The study of the neurobiology of syntax during awake surgery seems thus to be still at an early stage, in need of systematic, linguistically grounded investigations.

http://ift.tt/2rGBG80

### Abstract

This pilot study was aimed to value the feasibility and safety of Senhance Robotic Platform for hysterectomy in obese patients. Ten obese patients (30 < BMI < 40) underwent elective Senhance total extrafascial hysterectomy with bilateral salpingo-oophorectomy at the Division of Gynecologic Oncology of "Policlinico A. Gemelli" Foundation, Rome, Italy. Perioperative and postoperative outcomes data were recorded. The median age was 60 years (range 51–75) and the median BMI was 33.3 kg/m2 (range 30.4–38.3). The median uterine weight was 112.5 g (range 77–225). Indication to total hysterectomy was early-stage (FIGO Stage IA) endometrial cancer in 100% of patients. The median operative time (OT) was 110 min (70–200). The median docking time was 10.5 min (5–25). The median estimated blood loss was 100 mL (50–200). No conversions to laparotomy were recorded. No intra- and 30-day postoperative complications were registered. The median ileus was 17 h (12–36) and the median time to discharge was 2 days (1–4). The median VAS scores registered at 2, 4, 12, and 24 h were, respectively, 2 (1–3), 2 (1–3), 4 (1–8), and 3 (1–5). Our study results suggest that Senhance platform could be safe for hysterectomy even in obese patients. More clinical data are needed to determine whether this approach would offer any additional benefits in a new middle line between standard laparoscopy and robotics.

http://ift.tt/2rGRpnX

### Abstract

The electronic and optical properties of the rock-salt, CsCl-type, zinc-blende and wurtzite phases of TiN have been calculated by First-Principles study for relaxed and under pressure conditions. Calculations are based on the density functional theory and full potential augmented plane waves method by Generalized Gradient Approximation. The optical transitions in zero pressure are derived from the density of states and dielectric function. In addition, various optical characters, such as reflectivity, refraction and extinction indices, under positive and negative pressures are compared and contrasted. It is found that all mentioned phases of TiN are elastically stable and exhibit a rising trend in their plasmonic frequencies by increasing the pressure imposed on.

http://ift.tt/2rBMIQM

### Purpose

Metal implants have been used to treat adolescent idiopathic scoliosis since the 1960s. Only recently, however, it has the issue of metal-bone breakdown secondary to metal corrosion in situ come to light, raising concerns of possible long-term complications from the resulting metallosis and inflammation of spinal tissues. We present a case of a patient with neurological deficit, pain, and disability with Harrington rod in place for over 30 years, to bring attention to the issue of bio-corrosion of metal implants and its effect on human tissue. We call attention to the need for protocols to better diagnose and treat these patients.

### Methods

We provide a complete review of the history and clinical manifestations as well as serum metal, X-ray, and CT/myelogram test results.

### Results

A 52-year-old female with spinal fusion and Harrington rod presents with pain, lymphedema, disability, and neurological deficits including thoracic outlet syndrome, hyperreflexia, peripheral muscle weakness and atrophy, hypertonicity, Raynaud's phenomenon, and balance and gait abnormalities. Serum chromium levels were elevated (26.73 nmol). X-rays showed no evidence of rod breakdown. Serial X-rays can demonstrate subtle corrosive changes but were not available. Adhesive arachnoiditis was diagnosed via CT/myelogram.

### Conclusion

We hypothesize that bio-corrosion is present in this case and that it is associated with intraspinal metallosis. Trauma secondary to a motor vehicle accident, as well as arachnoiditis, and their possible effects on this case are outlined. Challenges in proper diagnosis and management are discussed.

http://ift.tt/2ty3IEc

### Background

The optimal surgical option for patients requiring bilateral hip replacement remains controversial. The purpose of this study was to compare surgical accuracy; functional outcome and health-related quality of life; and prosthetic-related complications and revision surgery of a simultaneous bilateral total hip arthroplasty (THA) with those of a staged bilateral THA with an interval between procedures <12 months.

### Methods

A total of 123 unselected consecutive patients (mean age, 43.3 years) who underwent bilateral THAs for osteonecrosis of the femoral head (ONFH) with a minimum follow-up of two years (mean, 60.2 months) were studied retrospectively; 63 simultaneous procedures served as a test group and 60 staged procedures served as a control group.

### Results

The mean postoperative leg-length discrepancy (LLD) and the percentage of patients who had an LLD >3 mm were significantly lower in the simultaneous group (P < 0.001 and P = 0.001, respectively). A higher number of cups within the safe zones, a higher correction rate, and a lower failure rate for the cup placement in the second-operated hip were also identified in the simultaneous group. The mean Harris hip score, EuroQol-5D index, and EuroQol-visual analogue scale score were all better in the simultaneous group at the latest follow-up (P < 0.001, in all comparisons). We found that the simultaneous procedure was associated with a lower incidence of postoperative prosthetic-related complications and revision surgery.

### Conclusions

We suggest that bilateral ONFH could be treated with a simultaneous THA rather than a staged THA to achieve a better surgical outcome.

http://ift.tt/2sDxHht

### Background

Despite the success of total knee arthroplasty (TKA) in reducing knee pain and improving functional disability, the management of acute postoperative pain is still unsatisfactory. This study was aimed to quantitatively analyze the possible correlations between inflammatory cytokines, muscle damage markers and acute postoperative pain following primary TKA.

### Methods

Patients scheduled for unilateral primary TKA were consecutively included, the serial changes of the numerical rating scale (NRS) at rest (NRSR) and at walking (NRSW), serum inflammatory cytokines and muscle damage markers were assessed before surgery (T0) and at postoperative day 1, 2, 3 and 5 (T1-T4, respectively); while pain disability questionnaire (PDQ) and synovial fluid inflammatory cytokines were evaluated at T0. The correlations between inflammatory cytokines, muscle damage markers and pain scores were examined, and Bonferroni correction was applied for multiple comparisons.

### Results

Ninety six patients were included for serum markers and pain evaluations at T0-T4, while 54 (56.25%) for synovial fluid cytokines at T0. The NRSR at T1 and T2 were positively correlated with preoperative NRSW, while the NRSW at T1 to T4 were positively correlated with preoperative NRSR, NRSW and PDQ (all p < 0.05). The NRSR was positively correlated with serum PGE2, IL-6, and CK at T1; the NRSW was positively correlated with serum CRP at T1, with PGE2 and IL-6 at T1 to T3, with CK at T2 and T4, and with Mb and LDH at T1 to T4 (all p < 0.003). Meanwhile, positive correlations were observed between preoperative NRSW and synovial fluid PGE2, IL-6, IL-8, or TNF-α, as well as between PDQ and PGE2 (all p < 0.003), but no associations between postoperative pain scores and preoperative synovial fluid cytokines was found (all p ≥ 0.003). Additionally, the NRSR at T1 and T2, and NRSW at T1 to T4 were positively correlated with body mass index (all p < 0.05).

### Conclusions

Serum inflammatory cytokines and muscle damage markers are positively correlated with acute postoperative pain following primary TKA, and the key cytokines (CRP, PGE2, and IL-6) and markers (Mb, CK and LDH) may serve as the targets for developing novel analgesic strategies.

http://ift.tt/2td6Gi5

### Background

Somatosensory profiling in affected and non-affected body regions can strengthen our insight regarding the underlying pain mechanisms, which can be valuable in treatment decision making and to improve outcomes, in patients with degenerative lumbar spine disorders pre-surgery. The aim was to describe somatosensory profiles in patients with degenerative lumbar spine disorders, to identify the proportion with altered somatosensory profile, and to analyze demographic characteristics, self-reported function, pain, and health pre- and 3 months post-surgery.

### Methods

In this prospective cohort study in a Spine Clinic, 105 patients scheduled for surgery for spinal stenosis, disc herniation, degenerative disc disease, or spondylolisthesis were consecutively recruited. Exclusion criteria were; indication for acute surgery or previous surgery at the same spinal level or severe grade of pathology. Quantitative sensory testing (QST) and self-reported function, pain, and health was measured pre- and 3 months post-surgery. The somatosensory profile included cold detection threshold, warmth detection threshold, cold pain threshold, heat pain threshold and pressure pain threshold in affected and non-affected body regions.

### Results

On a group level, the patients' somatosensory profiles were within the 95% confidence interval (CI) from normative reference data means. On an individual level, an altered somatosensory profile was defined as having two or more body regions (including a non-affected region) with QST values outside of normal ranges for reference data. The 23 patients (22%) with altered somatosensory profiles, with mostly loss of function, were older (P = 0.031), more often female (P = 0.005), had higher back and leg pain (P = 0.016, 0.020), lower mental health component summary score (SF-36 MCS) (P = 0.004) and larger pain distribution (P = 0.047), compared to others in the cohort. Post-surgery there was a tendency to worse pain, function and health in the group with altered somatosensory profile pre-surgery.

### Conclusions

On a group level, patients with degenerative lumbar spine disorders scheduled for surgery were within normal range for the QST measurements compared to reference values. On an individual level, an altered somatosensory profile outside of normal range in both affected and non-affected body regions occurred in 22% of patients, which may indicate disturbed somatosensory function. Those patients had mostly loss of sensory function and had worse self-reported outcome pre-surgery, compared to the rest of the cohort. Future prospective studies are needed to further examine whether these dimensions can be useful in predicting post-surgery outcome and guide need of additional treatments.

http://ift.tt/2sDcq7L

### In reply: Desflurane anesthesia and cognitive function

http://ift.tt/2sDBFXE

### Abstract

Glycans are essential for the maintenance of normal biological function, with alterations in glycan expression being a hallmark of cancer. Cancer stem cells (CSCs) are a subset of cells within a tumour capable of self-renewal, cellular differentiation and resistances to conventional therapies. As is the case with stem cells, marker proteins present on the cell surface are frequently used to identify and enrich CSCs, with the expression of these markers statistical correlating with the likelihood of cancer recurrence and overall patient survival. As such CSC markers are of high clinical relevance. The majority of markers currently used to identify CSC populations are glycoproteins, and although the diverse biological roles for many of these markers are known, the nature and function of the glycan moiety on these glycoproteins remains to be fully elucidated. This mini-review summarises our current knowledge regarding the types and extent of CSC marker glycosylation, and the various roles that these glycans play in CSC biology, including in mediating cell adhesion, metastasis, evading apoptosis, tear shear resistance, tumour growth, maintaining pluripotency, self-renewal, trafficking, maintaining stability, maintaining enzymatic activity and aiding epithelial mesenchymal transitioning. Given that CSCs markers have multiple diverse biological functions, and are potentially of significant diagnostic and therapeutic benefit the search for new markers that are uniquely expressed on CSCs is vital to selectively target/identify this subset of cancer cells. As such we have also outlined how high-throughput lectin microarrays can be used to successfully profile the glycosylation status of CSC and to identify glyco-markers unique to CSCs.

http://ift.tt/2sDBhIz

### Abstract

The Pan American Health Organization (PAHO) has promoted Integrated Health Services Networks as an innovative policy option for universal health coverage. In 2001, a Health Care model based on Health Attention Networks (RASs), and adopting the Primary Care Strategy (PHC), was designed in Porto Alegre/Brazil to meet health needs, by following the guidelines of the Unified Health System (SUS). The model advocates a view of health that entails preserving the autonomy of both individuals and groups and improving the management of a decentralized, regional and hierarchical system. In accordance with the Strategic Matrix, we introduced a called "Specialized Health Care Network" ESP, following the Methodology of Checkland and built the first "Problem Tree". By adopting a question- and -answer approach, the paper examines the lessons learned, by putting into effect a systematic step-by-step implementation of this Network. Since there are no bibliographical references to similar experiences in Brazil.

http://ift.tt/2tdf5ly

### Abstract

The ordered mesoporous silica SBA-15 has been applied in studies of ketorolac tromethamine adsorption and release. The SBA-15 materials with hexagonal and regular structure were obtained using a triblock copolymer Pluronic P123 as a template and TEOS as a silica source. Ketorolac tromethamine was adsorbed into SBA-15 silica nanochannels using ethanol as solvent. The physicochemical and textural properties of SBA-15 and ketorolac tromethamine/SBA-15 were characterized by X-ray diffraction, thermogravimetric analysis, transmission electron microscopy, fourier transform infrared spectroscopy and BET surface studies. Drug release was evaluated by soaking the loaded silica mesoporous material into a solution of HCl (0.1 N) at initial time (0–2 h) and buffer pH 7 at high times at 37 °C under continuous stirring. Oral commercial Keto tablets (Dolten®) and Keto solution (Keto power) were study for the contrast. Release studies were performed in order to evaluate the required therapeutic efficacy. SBA-15 provides significant improvement in the controlled release of ketorolac tromethamine.

### Graphical Abstract

Release profile of KETO from SBA-15/KETO and control releases.

http://ift.tt/2tyeM4o

### Abstract

Cerebral ischemia leads to multifaceted injury to the brain. A polytherapeutic drug that can be administered immediately after reperfusion may increase protection to the brain by simultaneously targeting multiple deleterious cascades. This study evaluated efficacy of the combination of three clinically approved drugs: lamotrigine, minocycline, and lovastatin, using two mouse models: global and focal cerebral ischemia induced by transient occlusion of the common carotid arteries or the middle cerebral artery, respectively. In vitro, the combination drug, but not single drug, protected neurons against oxygen-glucose deprivation (OGD)-induced cell death. The combination drug simultaneously targeted cell apoptosis and DNA damage induced by ischemia. Besides acting on neurons, the combination drug suppressed inflammatory processes in microglia and brain endothelial cells induced by ischemia. In a transient global ischemia model, the combination drug, but not single drug, suppressed microglial activation and inflammatory cytokine production, and reduced neuronal damage. In a transient focal ischemia model, the combination drug, but not single drug, attenuated brain infarction, suppressed infiltration of peripheral neutrophils, and reduced neurological deficits following ischemic stroke. In summary, the combination drug confers a broad-spectrum protection against ischemia/reperfusion (I/R) injury and could be a promising approach for early neuroprotection after out-of-hospital cardiac arrest or ischemic stroke.

http://ift.tt/2rqa5c2

### Background

A growing number of studies suggest that bariatric surgery is safe and effective for adolescents with severe obesity. However, surprisingly little is known about changes in dietary intake and eating behavior of adolescents who undergo bariatric surgery.

### Objective

Investigate changes in dietary intake and eating behavior of adolescents with obesity who underwent bariatric surgery (n = 119) or lifestyle modification (LM) (n = 169).

### Setting

University-based health systems

### Methods

A prospective investigation of 288 participants (219 female and 69 male) prior to bariatric surgery or LM and again 6, 12, and 24 months (surgery patients only) after treatment. Measures included changes in weight, macronutrient intake, eating behavior, and relevant demographic and physiological variables.

### Results

Adolescents who underwent bariatric surgery experienced significantly greater weight loss than those who received LM. The two groups differed in self-reported intake of a number of macronutrients at 6 and 12 months from baseline, but not total caloric intake. Patients treated with surgery, compared to those treated with LM, also reported significantly greater reductions in a number of disordered eating symptoms. After bariatric surgery, greater weight loss from postoperative month 6 to 12 was associated with self-reported weight consciousness, craving for sweets, and consumption of zinc.

### Conclusions

Adolescents who underwent bariatric surgery, compared to those who received LM, reported significantly greater reductions in weight after 1 year. They also reported greater reductions in disordered eating symptoms. These findings provide new information on changes in dietary intake and eating behavior among adolescents who undergo bariatric surgery.

http://ift.tt/2sbOHKn

### Abstract

Oxidized tyrosine products are commonly found in food with high protein content and have been demonstrated to cause damage of liver and kidney in our previous studies. Dityrosine (Dityr) is a typical oxidized tyrosine product. Due to its structural homology with thyroid hormones T3, we assumed that one of the endocrine systems most likely considered in connection with its disruption by Dityr may be the T3 action. T3 plays important roles in insulin synthesis, and thyroid hormone resistance (RTH) is associated with the impairment of glucose metabolism. Therefore, this study determined whether Dityr exposure impaired T3 function in pancreas leading to glucose metabolism disruption. After 10-week gavage with Dityr, mice exhibited impaired glucose tolerance and disturbed energy metabolism. The elevated free THs content in plasma, the up-regulation of THs synthesis-specific genes expressions in thyroid glands, and the increased thyroid follicles histology shapes and areas indicated that Dityr enhanced the THs synthesis in thyroid glands. In addition, Dityr-induced RTH, which reflected as elevated plasma free THs in the presence of unsuppressed thyroid stimulating hormone. The mRNA downregulation of membrane transporter of T3 (MCT8) and co-activator factors (RXRα, Src-1), together with the decreased protein level of thyroid hormone receptor β1 (TRβ1) in pancreas illustrated that the activation ability of T3 to downstream gene involved in insulin synthesis was suppressed by Dityr. In MIN-6 cell experiment, T3 improved glucose-stimulated insulin secretion by upregulating mRNA levels of insulin synthesis-related genes (Ins2, MafA, Pdx1) and T3 action-related genes, as well as increasing protein level of TRβ1. These data suggest that Dityr suppress T3-regulated insulin synthesis stimulated by glucose via an indirect way of decreasing sensibility to T3 in pancreas. All these findings indicate that Dityr can disrupt THs function in pancreas leading to glucose metabolism disorder.

http://ift.tt/2tyiSZY

### Abstract

Pseudomonas aeruginosa is the leading cause of pneumonia in intensive care units (ICUs), with multidrug-resistant (MDR) strains posing a serious threat. The aim of this study was to assess the clinical relevance of MDR Pseudomonas isolates in respiratory clinical specimens. A 5-year retrospective observational study in four medical-surgical ICUs from a referral hospital was carried out. Of 5667 adults admitted to the ICU, 69 had MDR-PA in respiratory samples: 31 were identified as having pneumonia (HAP/VAP): 21 ventilator-associated pneumonia (VAP) and ten hospital-acquired pneumonia (HAP). Twenty-one (67.7%) adults with MDR-PA HAP/VAP died after a median of 4 days (18 of the 21 deaths within 8 days), compared with one (2.6%) without pneumonia at day 8. In a Cox proportional regression model, MDR-PA pneumonia was an independent variable [adjusted hazard ratio (aHR) 5.92] associated with 30-day ICU mortality. Most strains (85.1%) were susceptible to amikacin and colistin. Resistance to beta-lactams (third-generation cephalosporins and piperacillin–tazobactam) ranged from 44.1% to 45.3%. Meropenem showed poor overall activity (MIC[50/90] 16/32 mg/dL), with 47.0% having a minimum inhibitory concentration (MIC) breakpoint >8 mg/L. Twenty-four (77.4%) HAP/VAP episodes received inappropriate empirical therapy. Although empirical combination therapy was associated with less inappropriate therapy than monotherapy (16.7% vs. 88.3%, p < 0.01), there was no difference in survival (30% vs. 33.3%, p = 0.8). Pneumonia was identified in one-third of adult ICU patients harbouring MDR-PA in respiratory clinical specimens. These patients have a 6-fold risk of (early) death compared to ventilator-associated tracheobronchitis (VAT) and respiratory colonisation. New antibiotics and adjuvant therapies are urgently needed to prevent and treat MDR-PA HAP/VAP.

http://ift.tt/2rGPpvH

### Purpose of Review

Colorectal cancer (CRC) is the fourth most common cancer in both men and women in the USA, resulting in over 55,000 deaths annually. Environmental and genetic factors influence the development of CRC, and inflammation is a critical hallmark of cancer that may arise from a variety of factors. While patients with inflammatory bowel disease (IBD) have a higher risk of developing CRC, sporadic CRCs may engender or be potentiated by inflammation as well. In this review, we focus on recent advances in basic and translational research utilizing murine models to understand the contribution of inflammatory signaling pathways to CRC.

### Recent Findings

We discuss advances in the utility of three-dimensional enteroid/colonoid/tumoroid cultures to understand immune-epithelial interactions in CRC, as well as the potential for utilizing patient-derived tumoroids for personalized therapies.

### Summary

This review underscores the importance of understanding the complex molecular mechanisms underlying inflammation in sporadic CRC and highlights up-and-coming or new avenues for CRC biomarkers or therapies.

http://ift.tt/2sbEe1y

### Abstract

Knowledge of nutrition among breast cancer patients is insufficient, despite their motivation to seek valid information about healthy food choices. This study examines the feasibility of nutrition education workshops for cancer survivors, to inform the design of a multi-center intervention. Fifty-nine female English-speaking breast cancer patients, who had completed treatment, were enrolled. Participants were randomized to the intervention or control group. The intervention group attended six nutrition education sessions, and the control group received brochures. Measurements were done at baseline and 3-month follow-up and included the Assessment Instrument for Breast Cancer (NLit-BCa), fruit/vegetable and general health literacy screeners. Height and weight were measured. Changes in nutrition literacy, health literacy, and food intake from baseline to follow-up (within-group change) were calculated for both groups (effect sizes were reported as Cohen's d). Participants were mostly white, with a mean age of 58 years, BMI of 31.6 kg/m2, and had college degrees. Follow-up rates were high (89% = control and 77% = intervention group). At baseline, participants scored high for most NLit-BCa assessment components except food portions in both groups. At the 3-month follow-up, effect sizes (d) on the NLit-BCa ranged from −0.5 to 0.16. The study met its recruitment goals within 6 months. Focus groups indicated that (a) attending six sessions was acceptable, (b) patients found social/emotional support, (c) improvements should include information for special diets and booster sessions. This pilot study suggests that the intervention was acceptable and that scaling up of this intervention is feasible and could provide benefit to breast cancer survivors.

http://ift.tt/2txPx1W

### Purpose

An optoelectronic surgical navigation system was used to detect small but measurable translational motion of human hip cadavers in high-range passive motions. Kinematic data were also examined to demonstrate the role of soft tissues in constraining hip translation.

### Methods

Twelve cadaver hips were scanned using CT, instrumented for navigation, and passively taken through motion assessment. Center of the femoral head was tracked in the acetabular coordinates. Maximum non-impinging translation of the femoral head for each specimen hip was reported. This was repeated for 5 tissue states: whole, exposed to the capsule, partially or fully incised capsule, resection of the ligamentum teres and labrectomy. Femoral motions were compared to the reported value for ideal ball and socket model.

### Results

Whole and exposed hips underwent maximal translations of $$3.9\pm 2.3$$ and $$3.1\pm 1.2$$  mm, respectively. These translational motions were statistically significantly different from reported value for a purely spherical joint, $$p=0.0005$$ . Further tissue removal almost always significantly increased maximum non-impingement translational motion with $$p<0.05$$ .

### Conclusion

We found subtle but definite translations in every cadaver hip. There was no consistent pattern of translation. It is possible to use the surgical navigation systems for the assessment of human hip kinematics intra-operatively and improve the treatment of total hip arthroplasty patients by the knowledge of the fact that their hips translate. Better procedure selection and implantation optimization may arise from improved understanding of the motion of this critically important human joint.

http://ift.tt/2slErxy

### Purpose

The main purpose of this systematic review was to investigate the effect of compression treatment on the perioperative course of ankle fractures and describe its effect on edema, pain, ankle joint mobility, wound healing complication, length of stay (LOS) and time to surgery (TTS). The aim was to suggest a recommendation to clinicians considering implementing compression therapy in the standard care of the ankle fracture patient, based on the existing literature.

### Methods

We conducted a systematic search of literature including studies concerning adult patients with unstable ankle fractures undergoing surgery, testing either intermittent pneumatic compression, compression bandage and/or compression stocking and reporting its effect on edema, pain, ankle joint mobility, wound healing complication, LOS and TTS. To conclude on data a narrative synthesis was performed.

### Results

The review included eight studies (451 patients). Seven studies found a significant effect on edema, two studies described a significant reduction in pain, one a positive effect on ankle movement, two a positive effect on wound healing, one a reduction in LOS and finally two studies reported reduction in TTS. A systematic bias assessment showed that the included studies had methodological limitations influencing the confidence in the effect estimate.

### Conclusions

Compression therapy has a beneficial effect on edema reduction and probably a positive effect on pain and ankle joint mobility, but with the methodological limitations in the included studies it is not possible to make a solid conclusion on the effect on wound healing, LOS and TTS.

http://ift.tt/2rBEKHx

### Radiological Response to the Locoregional Treatment in Hepatocellular Carcinoma: RECIST, mRECIST, and Others

http://ift.tt/2rpMiJ9