Comparative Studies on the Dissolution Profiles of Oral Ibuprofen Suspension and Commercial Tablets using Biopharmaceutical Classification System Criteria.

Abstract: In vitro dissolution studies for solid oral dosage forms have recently widened the scope to a variety of special dosage forms such as suspensions. For class II drugs, like Ibuprofen, it is very important to have discriminative methods for different formulations in physiological conditions of the gastrointestinal tract, which will identify different problems that compromise the drug bioavailability. In the present work, two agitation speeds have been performed in order to study ibuprofen suspension dissolution. The suspensions have been characterised relatively to particle size, density and solubility. The dissolution study was conducted using the following media: buffer pH 7.2, pH 6.8, 4.5 and 0.1 M HCl. For quantitative analysis, the UV/Vis spectrophotometry was used because this methodology had been adequately validated. The results show that 50 rpm was the adequate condition to discriminate the dissolution profile. The suspension kinetic release was found to be dependent on pH and was different compared to tablet release profile at the same experimental conditions. The ibuprofen release at pH 1.0 was the slowest.

Rivera-Leyva|J C|JC|
García-Flores|M|M|
Valladares-Méndez|A|A|
Orozco-Castellanos|L M|LM|
Martínez-Alfaro|M|M|

Dissolution
ibuprofen
suspension
particle size
validation
ultraviolet spectrophotometer


Severe multisensory speech integration deficits in high-functioning school-aged children with Autism Spectrum Disorder (ASD) and their resolution during early adolescence.

Abstract: Under noisy listening conditions, visualizing a speaker's articulations substantially improves speech intelligibility. This multisensory speech integration ability is crucial to effective communication, and the appropriate development of this capacity greatly impacts a child's ability to successfully navigate educational and social settings. Research shows that multisensory integration abilities continue developing late into childhood. The primary aim here was to track the development of these abilities in children with autism, since multisensory deficits are increasingly recognized as a component of the autism spectrum disorder (ASD) phenotype. The abilities of high-functioning ASD children (n = 84) to integrate seen and heard speech were assessed cross-sectionally, while environmental noise levels were systematically manipulated, comparing them with age-matched neurotypical children (n = 142). Severe integration deficits were uncovered in ASD, which were increasingly pronounced as background noise increased. These deficits were evident in school-aged ASD children (5-12 year olds), but were fully ameliorated in ASD children entering adolescence (13-15 year olds). The severity of multisensory deficits uncovered has important implications for educators and clinicians working in ASD. We consider the observation that the multisensory speech system recovers substantially in adolescence as an indication that it is likely amenable to intervention during earlier childhood, with potentially profound implications for the development of social communication abilities in ASD children.

Foxe|John J|JJ|
Molholm|Sophie|S|
Del Bene|Victor A|VA|
Frey|Hans-Peter|HP|
Russo|Natalie N|NN|
Blanco|Daniella|D|
Saint-Amour|Dave|D|
Ross|Lars A|LA|

D002659:Child Development Disorders, Pervasive

D011569:Psychiatric Status Rating Scales

autism spectrum disorders
development
cross-modal
sensory integration
speech-in-noise


The mitogen-activated protein kinase gene CcPmk1 is required for fungal growth, cell wall integrity and pathogenicity in Cytospora chrysosperma.

Abstract: Cytospora chrysosperma, the causal agent of canker disease in a wide range of woody plants, results in significant annual economic and ecological losses. Mitogen-activated protein kinase (MAPK) cascades are highly conserved signal transduction pathways that play a crucial role in mediating cellular responses to environmental and host signals in plant pathogenic fungi. In this study, we identified an ortholog of the Fus3/Kss1-related MAPK gene, CcPmk1, and characterized its functions in C. chrysosperma. The expression of CcPmk1 was highly induced by inoculation on poplar twigs, and targeted deletion of CcPmk1 resulted in the loss of pathogenicity, indicating that CcPmk1 is an important regulator of virulence. In addition, CcPmk1 deletion mutants (ΔCcPmk1) displayed reduced growth and conidiation, decreased fungal biomass production and hyperbranching. Furthermore, our results indicated that CcPmk1 deletion mutants exhibited hypersensitivity to cell wall inhibitors and cell wall-degrading enzymes. Correspondingly, the transcription of cell wall biosynthesis-related genes in the ΔCcPmk1 strain was downregulated compared to that in the wild-type strain. Moreover, we found that CcPmk1 could positively regulate the expression of several candidate effector encoding genes which were highly induced in planta. Hence, we hypothesized that CcPmk1 regulates the expression of a series of effectors to promote virulence. Overall, we concluded that the functions of CcPmk1 extend to fungal development, cell wall integrity and pathogenicity in C. chrysosperma.

Yu|Lu|L| Xiong|Dianguang|D| Han|Zhu|Z| Liang|Yingmei|Y| Tian|Chengming|C|

D015966:Gene Expression Regulation, Fungal

D019950:Mitogen-Activated Protein Kinase 1

Cell wall integrity
Pathogenicity
Cytospora chrysosperma
MAPK
Fungal development


Comparison of the functional and cardiovascular effects of home-based versus supervised hospital circuit training exercises in male wheelchair users with chronic paraplegia.

Abstract:
Objectives
The aim of this study was to compare the efficacy of home-based upper extremity circuit training exercises (CTEs) with supervised hospital program in male patients with traumatic complete paraplegia.

Patients and methods
Twenty men with paraplegia (mean age: 38±10.1 years; range, 30 to 43 years) between January 2007 and November 2007 were randomized into two groups. The first group had supervised hospital CTE program, whereas the second group had home-based CTE. The effects of the upper extremity CTE by using elastic bands 60 min per day, five days a week, for a total of eight weeks (70% maximal oxygen consumption [VO2max]) were examined. The Cybex was used for the isokinetic testing of the upper extremities. The VO2max and maximum heart rate (HR) were assessed using an arm ergometer. The Craig Handicap Report Technique Short Form (CHART-SF) was used for the evaluation of functional independence and mobility. Serum lipid profiles were measured.

Results
The mean injury duration was 7.9±2 years. The peak torque values of the upper extremities, VO2max, maximum HR, CHART-SF physical independence and mobility scores, and serum lipid profile were all improved in both groups (p<0.05). There were no significant differences in terms of the increase in the muscle strength and serum lipid levels between the groups (p>0.05). The improvement in the VO2max, physical independence, and mobility scores were greater in the supervised exercise group.

Conclusion
Upper extremity strength, cardiovascular endurance, and lipid profile were improved after supervised and home-based CTE in the men with paraplegia. Home-based exercise programs may be good alternatives to the hospital rehabilitation for this patient population.

Kesiktaş|Fatma Nur|FN|
Kaşıkçıoğlu|Erdem|E|
Paker|Nurdan|N|
Bayraktar|Bülent|B|
Karan|Ayşe|A|
Ketenci|Ayşegül|A|
Müslümanoğlu|Lütfiye|L|

Exercise
male
wheelchair
paraplegia
upper extremity
maximal oxygen consumption
spinal cord injury


Genomic Analysis Using Bayesian Methods under Different Genotyping Platforms in Korean Duroc Pigs.

Abstract: Genomic evaluation has been widely applied to several species using commercial single nucleotide polymorphism (SNP) genotyping platforms. This study investigated the informative genomic regions and the efficiency of genomic prediction by using two Bayesian approaches (BayesB and BayesC) under two moderate-density SNP genotyping panels in Korean Duroc pigs. Growth and production records of 1026 individuals were genotyped using two medium-density, SNP genotyping platforms: Illumina60K and GeneSeek80K. These platforms consisted of 61,565 and 68,528 SNP markers, respectively. The deregressed estimated breeding values (DEBVs) derived from estimated breeding values (EBVs) and their reliabilities were taken as response variables. Two Bayesian approaches were implemented to perform the genome-wide association study (GWAS) and genomic prediction. Multiple significant regions for days to 90 kg (DAYS), lean muscle area (LMA), and lean percent (PCL) were detected. The most significant SNP marker, located near the MC4R gene, was detected using GeneSeek80K. Accuracy of genomic predictions was higher using the GeneSeek80K SNP panel for DAYS (Δ2%) and LMA (Δ2-3%) with two response variables, with no gains in accuracy by the Bayesian approaches in four growth and production-related traits. Genomic prediction is best derived from DEBVs including parental information as a response variable between two DEBVs regardless of the genotyping platform and the Bayesian method for genomic prediction accuracy in Korean Duroc pig breeding.

Lee|Jungjae|J|0000-0002-6145-8862 Kim|Yongmin|Y|0000-0003-3163-8077 Cho|Eunseok|E| Cho|Kyuho|K| Sa|Soojin|S| Kim|Youngsin|Y| Choi|Jungwoo|J| Kim|Jinsoo|J| Hong|Junki|J| Choi|Taejeong|T|

Duroc
single nucleotide polymorphism
genome-wide association study
genomic breeding value


Systolic-diastolic functional coupling in healthy children and in those with dilated cardiomyopathy.

Abstract: Systolic and diastolic function affect dilated cardiomyopathy (DCM) outcomes. However, systolic-diastolic coupling, as a distinct characteristic, may itself affect function but is poorly characterized. We hypothesized that echocardiographic left ventricular (LV) longitudinal systolic tissue velocities (S') correlate with diastolic longitudinal velocities (E') and that their relationship is associated with ventricular function and that this relationship is impaired in pediatric DCM. We analyzed data from the Pediatric Heart Network Ventricular Volume Variability study, using linear regression and generalized additive modeling to assess relationships between S' and E' at the lateral and septal mitral annulus. We explored relationships between the systolic:diastolic (S:D) coupling ratio (S':E' relative to age) and ventricular function. Up to 4 echocardiograms from 130 DCM patients (mean age: 9.3 ± 6.1 yr) and 1 echocardiogram from each of 591 healthy controls were analyzed. S' and E' were linearly related in controls (r = 0.64, P < 0.001) and DCM (r = 0.83, P < 0.001). In DCM, the magnitude of association between S' and E' was reduced with progressive ventricular remodeling. The S:D ratio was more strongly associated with LV function in controls vs. DCM. The septal S:D ratio was higher (presumed worse) in DCM vs. controls (0.69 ± 0.13 vs. 0.62 ± 0.12, P = 0.001). A higher septal S:D ratio was associated with worse LV dimensions (parameter estimate: 0.0061, P = 0.004), mass (parameter estimate: 0.0074, P = 0.002), ejection fraction (parameter estimate: -0.0303, P = 0.024), and inflow propagation (parameter estimate: -0.3538, P < .001). S:D coupling becomes weaker in DCM with LV remodeling and dysfunction. The S:D coupling ratio may be useful to assess coupling, warranting study in relation to patient outcomes.

Friedberg|Mark K|MK|
Margossian|Renee|R|
Lu|Minmin|M|
Mercer-Rosa|Laura|L|
Henderson|Heather T|HT|
Nutting|Arni|A|
Friedman|Kevin|K|
Molina|Kimberly M|KM|
Altmann|Karen|K|
Canter|Charles|C|
Sleeper|Lynn A|LA|
Colan|Steven D|SD|
|||

cardiomyopathy systole diastole pediatrics echocardiography


Quinolactacin Biosynthesis Involves Non-Ribosomal-Peptide-Synthetase-Catalyzed Dieckmann Condensation to Form the Quinolone-γ-lactam Hybrid.

Abstract: Quinolactacins are novel fungal alkaloids that feature a quinolone-γ-lactam hybrid, which is a potential pharmacophore for the treatment of cancer and Alzheimer's disease. Herein, we report the identification of the quinolactacin A2 biosynthetic gene cluster and elucidate the enzymatic basis for the formation of the quinolone-γ-lactam structure. We reveal an unusual β-keto acid (N-methyl-2-aminobenzoylacetate) precursor that is derived from the primary metabolite l-kynurenine via methylation, oxidative decarboxylation, and amide hydrolysis reactions. In vitro assays reveal two single-module non-ribosomal peptide synthetases (NRPs) that incorporate the β-keto acid and l-isoleucine, followed by Dieckmann condensation, to form the quinolone-γ-lactam. Notably, the bioconversion from l-kynurenine to the β-keto acid is a unique strategy employed by nature to decouple R*-domain-containing NRPS from the polyketide synthase (PKS) machinery, expanding the paradigm for the biosynthesis of quinolone-γ-lactam natural products via Dieckmann condensation.

Zhao|Fanglong|F| Liu|Zhiwen|Z| Yang|Shuyuan|S| Ding|Ning|N| Gao|Xue|X|0000-0003-3213-9704

Dieckmann condensation
non-ribosomal peptide synthetases
natural products
biological and medicinal chemistry
enzymes


Expression of antioxidant genes in broiler chickens fed nettle (Urtica dioica) and its link with pulmonary hypertension.

Abstract: Nettle (Urtica dioica) contains a wide range of chemical constituents that confer a strong antioxidant capacity to the plant. The present study was to investigate the antioxidant gene expression and pulmonary hypertensive responses of broiler chickens to U. dioica. A total of 240 one-d-old broilers (Ross 308) were randomly assigned to 4 dietary levels of U. dioica (0, 0.5%, 1% and 1.5%). Birds were reared for 6 wk in a high altitude region (2,100 m). The results showed a significant relative overexpression (target gene/β-actin as the arbitrary unit) of catalase (CAT) and superoxide dismutase 1 (SOD1) in the liver and lung of the chickens fed U. dioica. Lipid peroxidation was significantly suppressed, as reflected in reduced circulatory concentrations of malondialdehyde (MDA) in the birds fed U. dioica. These birds also had significantly (P < 0.05) higher serum nitric oxide (NO) concentrations than those in the control group. Feeding U. dioica at 1% and 1.5% also attenuated the right ventricular hypertrophy (reflected in the lower right to total ventricular weight ratio), which was associated with a significant lower rate of mortality from pulmonary hypertension syndrome. Feeding U. dioica led to an upregulation of hepatic and pulmonary antioxidant genes.

Chicken
Urtica dioica
Antioxidant enzymes
Right ventricular failure


A spliced form of CD44 expresses the unique glycan that is recognized by the prostate cancer specific antibody F77.

Abstract: Prostate cancer is the most common cancer occurring in men in the United States. The monoclonal antibody F77 that was originally developed in our laboratory recognizes mainly glycolipids as well as O-linked glycosylation on proteins in prostate cancer cells. We have identified a spliced form of glycoprotein CD44 as one critical protein expressing the F77 antigen. The F77-specific glycosylation occurs on multiple potential glycosylation sites on the CD44 protein encoded by the fourteenth exon. CD44 is a tumor stem cell marker and is known to induce tumor stemness and metastasis. Knockdown of CD44 or FUT1 genes dramatically reduced F77-induced apoptosis in prostate cancer cell lines. We developed an ELISA using both a CD44 antibody and F77 to identify the special form of glycosylated CD44 from prostate cancer cells as well as from serum samples of prostate cancer patients. These results reveal a CD44-dependent mechanism for F77 to induce tumor cell apoptosis, and a new strategy for the detection of glycosylated CD44 proteins secreted by prostate cancer cells.

Chen|Xi|X|
Nagai|Yasuhiro|Y|
Zhu|Zhiqiang|Z|
Ruan|Hang|H|
Peehl|Donna M|DM|
Greene|Mark I|MI|
Zhang|Hongtao|H|

CD44
prostate cancer
antibody
O-linked glycosylation
post-translational modification


The Effect of Opiates on Bone Formation and Bone Healing.

Abstract:
PURPOSE OF REVIEW
Opioids have been shown to be associated with an increased risk of fracture. The purpose of this paper is to review recent research into the effects of opioids on bone formation and bone healing in animal models and in human studies.

RECENT FINDINGS
Most opioids, such as morphine and fentanyl, negatively affected bone remodeling and bone healing in animal models. Conversely, remifentanil has been recently shown to promote in vitro osteoblast differentiation and to inhibit differentiation and maturation of osteoclasts, therefore reducing bone resorption. According to the possible negative role of opioids in bone healing, opioid antagonists have been shown to enhance bone mineralization, suggesting a possible therapeutic role in the future for osteoporosis. Other neuropeptides, such as the vasoactive intestinal peptide (VIP) and the neuropeptide Y (NPY), have been proved to promote osteogenesis. The increased risk of fractures among opioid users may be related to their central nervous system side effects or to the reduced bone density, partly due to their endocrine effects, and partly to their direct activity on bone cells. Clinical data strongly suggested a potential negative effect of opioids in bone healing. The risk of nonunion fracture is significantly increased in opioid users, and bone mass density was reduced in patients under long-term opioid treatment. The direct effects of opioids on bone remodeling appears evident from these reports. Not all opioids have the same potential for negatively impacting bone healing. Opioid antagonists may increase bone density and could represent a possible future treatment for low bone mass density pathologies. However, further trials are warranted to clarify the clinical relevance of these emerging findings from animal studies.

Coluzzi|Flaminia|F|
Scerpa|Maria Sole|MS|
Centanni|Marco|M|

D000701:Analgesics, Opioid
D000818:Animals
D016723:Bone Remodeling
D002113:Calcification, Physiologic
D017102:Fracture Healing
D050723:Fractures, Bone
D005599:Fractures, Ununited
D006801:Humans
D009292:Narcotic Antagonists
D009478:Neuropeptide Y
D010012:Osteogenesis
D014660:Vasoactive Intestinal Peptide

Bone
Bone healing
Opioids
Fracture
Osteoblasts
OPIAD


Krüppel-like factors: Crippling and un-crippling metabolic pathways.

Abstract: Krüppel-like factors (KLFs) are DNA-binding transcriptional factors that regulate various pathways that control metabolism and other cellular mechanisms. Various KLF isoforms have been associated with cellular, organ or systemic metabolism. Altered expression or activation of KLFs has been linked to metabolic abnormalities, such as obesity and diabetes, as well as with heart failure. In this review article we summarize the metabolic functions of KLFs, as well as the networks of different KLF isoforms that jointly regulate metabolism in health and disease.

Pollak|Nina M|NM|
Hoffman|Matthew|M|
Goldberg|Ira J|IJ|
Drosatos|Konstantinos|K|

Krüppel-like factors
metabolism
obesity
diabetes
heart failure


Air Pollution and Emergency Department Visits for Disease of the Genitourinary System.

Abstract: The aim of this study is to determine associations between ambient air pollution and the number of emergency department (ED) visits for diseases of the genitourinary tract in Toronto, Canada. We used the National Ambulatory Care Reporting System (NACRS) database to obtain the related ED visits and developed statistical models using daily data on ED visits, temperature, relative humidity, and outdoor air pollution concentration levels. The NACRS database contains data on hospital-based and community-based ambulatory care. The environmental data were retrieved from the National Air Pollution Surveillance (NAPS) program. The NAPS is the main source of ambient air quality data in Canada. We considered 2 air quality health indexes and 6 air pollutants: daily means of fine particulate matter PM2.5, O3, CO, NO2, SO2, and also maximum 8-hour average ozone. For every air pollutant, we fit 270 models (15 lags × 18 strata). We found that same-day air pollution concentrations have the highest number of statistically significantly positive associations with ED visits for genitourinary health outcomes. A total of 133 positive associations were identified over the 14 days lag. In subgroup (strata) analysis, females older than 60 years of age were found to have the most positive associations. In particular, nitrogen dioxide was found to be highly associated with ED visits for females over 60; an increase in NO2 was associated with an increased relative risk (RR) of ED visits when lagged over 0, 1, and 2 days (RR = 1.040 [95% confidence interval: 1.028, 1.052], 1.020 [1.009, 1.032], and 1.025 [1.013, 1.036], respectively). The values of risks are reported for a 1 interquartile range increase in concentration (8.8 ppb). Our results suggest that urban ambient air pollution affect the number of ED visits due to genitourinary system conditions.

Air pollution
genitourinary system
concentration
strata
Poisson
case-crossover
counts
time-series


Associations between Self-Disorders and First-Rank Symptoms: An Empirical Study.

Abstract:
BACKGROUND
The diagnostic weight of the first-rank symptoms was deemphasized in DSM-5 and a similar change is expected in ICD-11. This change was motivated by a lack of solid, empirical evidence of the diagnostic significance of first-rank symptoms for schizophrenia. Yet, it seems that Schneider's original concept of first-rank symptoms was overly simplified when it was introduced in DSM-III. Specifically, it was overlooked that first-rank symptoms, in Schneider's understanding, fundamentally involve a disorder of the self. The aim here is to empirically test Schneider's claim that first-rank symptoms involve self-disorders.

METHODS
In a modified, cross-sectional study of 98 first-admission patients, the relation between lifetime presence of first-rank symptoms and self-disorders was examined. Self-disorders were examined with the EASE (Examination of Anomalous Self-Experiences).

RESULTS
We found an odds ratio of 1.56 (95% CI 1.10-2.21) for having first-rank symptoms for each 5-point increase in the EASE (measuring self-disorder) using a generalized linear mixed model regression. We did not find first-rank symptoms in the absence of self-disorders.

CONCLUSION
The close relation between first-rank symptoms and self-disorders seems to support Schneider's original concept of first-rank symptoms. We suggest that first-rank symptoms occurring without the pervasively altered self-experiences might not be different from other psychotic phenomena in terms of their diagnostic significance. Awareness of self-disorders can help clinicians in assessing and detecting first-rank symptoms.

Nordgaard|Julie|J|
Henriksen|Mads Gram|MG|
Berge|Jonas|J|
Siersbæk Nilsson|Lars|L|

D039721:Diagnostic and Statistical Manual of Mental Disorders

EASE
Anomalous self-experience
Diagnoses
Psychosis
Schizotypal disorder
Schneiderian


On-Site Blackwater Treatment Fosters Microbial Groups and Functions to Efficiently and Robustly Recover Carbon and Nutrients.

Abstract: Wastewater is considered a renewable resource water and energy. An advantage of decentralized sanitation systems is the separation of the blackwater (BW) stream, contaminated with human pathogens, from the remaining household water. However, the composition and functions of the microbial community in BW are not known. In this study, we used shotgun metagenomics to assess the dynamics of microbial community structure and function throughout a new BW anaerobic digestion system installed at The Netherlands Institute of Ecology. Samples from the influent (BW), primary effluent (anaerobic digested BW), sludge and final effluent of the pilot upflow anaerobic sludge blanket (UASB) reactor and microalgae pilot tubular photobioreactor (PBR) were analyzed. Our results showed a decrease in microbial richness and diversity followed by a decrease in functional complexity and co-occurrence along the different modules of the bioreactor. The microbial diversity and function decrease were reflected both changes in substrate composition and wash conditions. Our wastewater treatment system also decreased microbial functions related to pathogenesis. In summary, the new sanitation system studied here fosters microbial groups and functions that allow the system to efficiently and robustly recover carbon and nutrients while reducing pathogenic groups, ultimately generating a final effluent safe for discharge and reuse.

shotgun metagenomics
Chlorella sorokiniana
blackwater microbiome
nitrogen
phosphorus


Corneal confocal microscopy anomalies associated with cowden syndrome: a case report.

Abstract:
PURPOSE
To describe bilateral corneal alterations through confocal microscopy in a patient affected by Cowden syndrome (CS).

METHODS
Evaluation of Schirmer's, fluorescein, and lissamine green dye tests. Confocal microscopy was performed in both eyes to investigate corneal abnormalities.

RESULTS
Slit lamp observation showed the focal involvement of anterior stromal and epithelial layers. Schirmer's, fluorescein, and lissamine green dye test results were regular, while corneal confocal examination confirmed the disorganization of anterior stromal and epithelial layers in both eyes.

CONCLUSION
CS is a rare autosomal-dominant systemic disorder. In our case, confocal analysis revealed predominance of alterations in the anterior stromal corneal layer, showing an increase of reflectivity, and a totally unstructured architecture in the epithelium layer. Even though the main purpose remains the prevention and the early diagnosis of different systemic tumors that could occur in affected patients, corneal confocal evaluation could play an important role in the early diagnosis of this rare disease.

Sbordone|Sandro|S|
Savastano|Alfonso|A|
Savastano|Maria Cristina|MC|
Romano|Vito|V|
Bifani|Mario|M|
Savastano|Silvio|S|

Corneal confocal microscopy
Cowden syndrome
Corneal alterations
Multiple hamartoma syndrome


A pilot study of the impact of an exercise intervention on brain structure, cognition, and psychosocial symptoms in individuals with relapsing-remitting multiple sclerosis.

Abstract:
BACKGROUND
Despite pharmacological treatment, many individuals with multiple sclerosis (MS) continue to experience symptoms and medication side effects. Exercise holds promise for MS, but changes in brain structure following exercise have not been thoroughly investigated, and important cognitive and psychosocial variables are rarely primary outcomes. The aim of this pilot study was to investigate whether a 12-week exercise intervention would improve white matter integrity in the brain, or cognition, symptoms of fatigue, and depressed mood for individuals with relapsing-remitting MS (RRMS).

METHOD
Thirteen participants completed 12 weeks of speeded walking. Baseline and post-intervention testing included 3T diffusion tensor imaging (DTI) to assess white matter and neuropsychological testing to assess cognition, fatigue, and mood. Image pre-processing and analyses were performed in functional magnetic resonance imaging of the Brain Software Library.

RESULTS
Post-intervention, there were no significant changes in white matter compared to baseline. Post-intervention, individuals with RRMS performed significantly better on the Symbol Digit Modalities Test (SDMT), reported fewer perceived memory problems, and endorsed less fatigue. Performance was not significantly different on Trails or Digit Span, and there were no significant changes in reports of mood.

CONCLUSION
Although 12 weeks of speeded walking did not improve white matter integrity, exercise may hold promise for managing some symptoms of RRMS in the context of this study population.

Exercise
Cognition
Multiple sclerosis
Fatigue
Depressed mood
Diffusion tensor imaging
Symptom management


Enhanced expression of hydroxylated ceramide in well-differentiated endometrial adenocarcinoma.

Abstract: Based on our previous analysis of neutral glycolipids in the human endometrium, the present authors already reported that the concentrations of glucosylceramide, lactosylceramide and globotriaosylceramide (Gb3Cer), in which both fatty acids and sphingosines in the ceramides are hydroxylated, exhibit a marked increase during the luteal phase of the menstrual cycle. It is also well known that poorly differentiated endometrial adenocarcinoma exhibits a more rapid progression and a worse response to therapy than well-differentiated endometrial adenocarcinoma. To examine the molecular background of well-differentiated and poorly differentiated cancers, the levels of neutral glycolipids in tumor tissues from endometrial carcinoma displaying different degrees of differentiation were measured. The composition of neutral glycolipids in tumor tissues was determined, and ceramide structures that were specifically expressed in well-differentiated endometrial carcinomas were investigated using biochemical analytical methods, including lipid extraction, enzyme digestion, thin-layer chromatography (TLC), gas-liquid chromatography and mass spectrometry. Well-differentiated adenocarcinoma contained numerous structurally unknown glycolipids that exhibited slower migration than globotetraosylceramide (Gb4Cer). In the case of Gb3Cer, three bands appeared on TLC in well-differentiated cancer, but only two bands appeared in the poorly-differentiated cancer. This difference was associated with the fatty acid composition of ceramide, since non-hydroxy fatty acids with ≥20 carbon atoms were increased in well-differentiated cancer, while α-hydroxy fatty acids were increased in poorly differentiated cancer. Similarly, there were two bands on TLC of Gb4Cer from well-differentiated cancer, but only one band in poorly differentiated cancer, and the long-chain base of ceramide was observed to contain phytosphingosine in well-differentiated cancer. It was demonstrated in endometrial cancer that the structure of ceramide molecules changes with the extent of tumor differentiation. These findings suggest that hydroxylated ceramides contribute to the well-differentiated phenotype of endometrial adenocarcinoma.

Tajima|Toshiki|T| Miyazawa|Masaki|M| Hayashi|Masaru|M| Asai|Satoshi|S| Ikeda|Masae|M| Shida|Masako|M| Hirasawa|Takeshi|T| Iwamori|Masao|M| Mikami|Mikio|M|

glycolipid
differentiation
α-hydroxy fatty acid
phytosphingosine
endometrial cancer


Comparative Secretome and Functional Analyses Reveal Glycoside Hydrolase Family 30 and Cysteine Peptidase as Virulence Determinants in the Pinewood Nematode Bursaphelenchus xylophilus.

Abstract: Pine wilt disease, caused by the pinewood nematode, Bursaphelenchus xylophilus, is one of the world's most serious tree diseases. Although the B. xylophilus whole-genome sequence and comprehensive secretome profile have been determined over the past decade, it remains unclear what molecules are critical in pine wilt disease and govern B. xylophilus virulence in host pine trees. Here, a comparative secretome analysis among four isolates of B. xylophilus with distinct virulence levels was performed to identify virulence determinants. The four candidate virulence determinants of B. xylophilus highly secreted in virulent isolates included lipase (Bx-lip1), glycoside hydrolase family 30 (Bx-GH30), and two C1A family cysteine peptidases (Bx-CAT1 and Bx-CAT2). To validate the quantitative differences in the four potential virulence determinants among virulence groups at the protein level, we used real-time reverse-transcription polymerase chain reaction analysis to investigate these determinants at the transcript level at three time points: pre-inoculation, 3 days after inoculation (dai), and 7 dai into pine seedlings. The transcript levels of Bx-CAT1, Bx-CAT2, and Bx-GH30 were significantly higher in virulent isolates than in avirulent isolates at pre-inoculation and 3 dai. A subsequent leaf-disk assay based on transient overexpression in Nicotiana benthamiana revealed that the GH30 candidate virulent factor caused cell death in the plant. Furthermore, we demonstrated that Bx-CAT2 was involved in nutrient uptake for fungal feeding via soaking-mediated RNA interference. These findings indicate that the secreted proteins Bx-GH30 and Bx-CAT2 contribute to B. xylophilus virulence in host pine trees and may be involved in pine wilt disease.

Shinya|Ryoji|R| Kirino|Haru|H| Morisaka|Hironobu|H| Takeuchi-Kaneko|Yuko|Y| Futai|Kazuyoshi|K| Ueda|Mitsuyoshi|M|

glycoside hydrolase family 30
cysteine peptidase
virulence determinant
pinewood nematode
Nicotiana benthamiana
secreted protein


Harmine suppresses the proliferation of pancreatic cancer cells and sensitizes pancreatic cancer to gemcitabine treatment.

Abstract:
Purpose
Pancreatic carcinoma is one of the most deadliest types of cancer, and relatively insensitive to the currently available chemotherapy. Thus, the discovery of novel therapeutic agents to prolong the survival times of patients with pancreatic cancer is urgently required.

Methods
Cell proliferation was assessed using the sulforhodamine B and cell clone formation assay, apoptosis was analyzed through Annexin V/PI staining, analysis of cell cycle distribution was determined by PI staining, and the expression of proteins was detected via Western blotting.

Results
Our data showed that harmine exerted an anti-proliferative effect and cell cycle arrest at G2/M in pancreatic cancer cells. Meanwhile, harmine plus gemcitabine showed strong synergy in inhibiting the proliferation of pancreatic cancer cells. Furthermore, harmine induced apoptosis and enhanced the gemcitabine-induced apoptosis in pancreatic cancer cells. The AKT/mTOR pathway is involved in mechanisms of gemcitabine resistance in pancreatic cancer cells, our data demonstrated that harmine plus gemcitabine significantly suppressed the AKT/mTOR signaling pathway.

Conclusion
Harmine may be a potential candidate for the treatment of pancreatic cancer. Morever, the combination of harmine with gemcitabine appears to be an attractive option for the treatment of patients with pancreatic cancer.

Wu|Lin-Wen|LW| Zhang|Jian-Kang|JK| Rao|Mingjun|M| Zhang|Zuo-Yan|ZY| Zhu|Hua-Jian|HJ| Zhang|Chong|C|

harmine
pancreatic cancer
gemcitabine
AKT/mTOR
combination


Nociceptor Sensory Neuron-Immune Interactions in Pain and Inflammation.

Abstract: Nociceptor sensory neurons protect organisms from danger by eliciting pain and driving avoidance. Pain also accompanies many types of inflammation and injury. It is increasingly clear that active crosstalk occurs between nociceptor neurons and the immune system to regulate pain, host defense, and inflammatory diseases. Immune cells at peripheral nerve terminals and within the spinal cord release mediators that modulate mechanical and thermal sensitivity. In turn, nociceptor neurons release neuropeptides and neurotransmitters from nerve terminals that regulate vascular, innate, and adaptive immune cell responses. Therefore, the dialog between nociceptor neurons and the immune system is a fundamental aspect of inflammation, both acute and chronic. A better understanding of these interactions could produce approaches to treat chronic pain and inflammatory diseases.

Pinho-Ribeiro|Felipe A|FA|
Verri|Waldiceu A|WA|
Chiu|Isaac M|IM|

nociceptor
pain
inflammation
sensory neuron
neuroimmunology


Structure of bacterial phospholipid transporter MlaFEDB with substrate bound.

Abstract: In double-membraned bacteria, phospholipid transport across the cell envelope is critical to maintain the outer membrane barrier, which plays a key role in virulence and antibiotic resistance. An MCE transport system called Mla has been implicated in phospholipid trafficking and outer membrane integrity, and includes an ABC transporter, MlaFEDB. The transmembrane subunit, MlaE, has minimal sequence similarity to other transporters, and the structure of the entire inner-membrane MlaFEDB complex remains unknown. Here, we report the cryo-EM structure of MlaFEDB at 3.05 Å resolution, revealing distant relationships to the LPS and MacAB transporters, as well as the eukaryotic ABCA/ABCG families. A continuous transport pathway extends from the MlaE substrate-binding site, through the channel of MlaD, and into the periplasm. Unexpectedly, two phospholipids are bound to MlaFEDB, suggesting that multiple lipid substrates may be transported each cycle. Our structure provides mechanistic insight into substrate recognition and transport by MlaFEDB.

cryo-EM
E. coli
bacterial outer membrane
lipid transport
mla pathway
molecular biophysics
structural biology


Integrin α4β7 in HIV-1 infection: A critical review.

Abstract: Over the past decade, a series of observations linking α4β7, the principal gut-homing integrin, with various aspects of HIV-1 infection have generated considerable interest in the field of HIV-1 research. After the initial report that the major HIV-1 envelope glycoprotein, gp120, can bind to α4β7, intensive research efforts have been focused on the role of α4β7 as a key factor in HIV-1 pathogenesis and as a potential target for prevention and treatment. The interaction between α4β7 and its natural ligand, MAdCAM-1, directs infected CD4+ T cells and HIV-1 virions carrying incorporated α4β7 to the gut mucosa, which may facilitate HIV-1 seeding and replication in the intestinal compartment during the early stages of infection. In addition, cells that express high levels of α4β7, such as Th17 cells, represent preferential targets for infection, and their frequency in the circulation was shown to correlate with susceptibility to HIV-1 infection and disease progression. A number of in vivo studies in nonhuman primates have investigated whether blockage of α4β7 may affect SIV transmission and pathogenesis. Administration of a primatized anti-α4β7 antibody that blocks MAdCAM-1 binding to α4β7 was reported to reduce SIV mucosal transmission in rhesus macaques. However, the mechanism responsible for such a protective effect is still undefined, and conflicting results have been reported on the effects of the same antibody, in combination with ART, during the early chronic phase of SIV infection. Thus, despite a series of tantalizing results accrued over the past decade, the jury is still out on the role of α4β7 in HIV-1 infection.

α4β7
HIV-1 infection
anti-α4β7 therapy
gut homing


Formulation and In-vivo Pharmacokinetic Consideration of Intranasal Microemulsion and Mucoadhesive Microemulsion of Rivastigmine for Brain Targeting.

Abstract:
PURPOSE
Presence of tight junctions in blood brain barrier (BBB) pose a major hurdle for delivery of drug and severely affects adequate therapeutic concentration to reach the brain. In present work, we have selected Rivastigmine hydrogen tartrate (RHT), a reversible cholinesterase inhibitor, which exhibits extensive first-pass metabolism, resulting in limited absolute bioavailability (36%). RHT shows extremely low aqueous solubility and poor penetration, resulting in inadequate concentration reaching the brain, thus necessitating frequent oral dosing. To overcome these problems of RHT, microemulsion (ME) and mucoadhesive microemulsion (MME) of RHT were formulated for brain targeting via intranasal delivery route and compared on the basis of in vivo pharmacokinetics.

METHODS
ME and MME formulations containing RHT were developed by water titration method. Characterization of ME and MME was done for various physicochemical parameters, nasal spray pattern, and in vivo pharmacokinetics quantitatively and qualitatively (gamma scintigraphy studies).

RESULTS
The developed ME and MME were transparent having globule size approximately in the range of 53-55 nm. Pharmacokinetic studies showed higher values for Cmax and DTP for intranasal RHT: CH-ME over RHT-ME, thus indicating the effect of chitosan in modulating tight junctions, thereby enhanced paracellular transport of RHT.

CONCLUSION
Gamma scintigraphy and in vivo pharmacokinetic study suggested enhanced RHT concentration, upon intranasal administration of RHT:CH-ME, compare with other groups administered formulations intranasally. These findings suggested the potential of non-invasive intranasal route for brain delivery, especially for therapeutics, facing challenges in oral administration.

D002851:Chromatography, High Pressure Liquid

microemulsion
rivastigmine
brain targeting
intranasal route
alzheimer’s disease


Dose-dependent neurotoxicity caused by the addition of perineural dexmedetomidine to ropivacaine for continuous femoral nerve block in rabbits.

Abstract:
OBJECTIVE
This study was designed to evaluate the neurotoxicity of dexmedetomidine combined with ropivacaine for continuous femoral nerve block in rabbits.

METHODS
Thirty New Zealand rabbits were randomly divided into 5 groups of 6 rabbits each and received a continuous femoral nerve block with saline; 0.25% ropivacaine; or 1, 2, or 3 µg/mL of dexmedetomidine added to 0.25% ropivacaine (Groups A-E, respectively). Sensory and motor function was assessed after the nerve block. The rabbits were anesthetized and killed after 48 hours of a continuous femoral nerve block, and the femoral nerves were removed for light and electron microscopy analyses.

RESULTS
The behavior scores were highest in Group A at 2 and 6 hours after injection. The scores were higher in Groups B and C than in Groups D and E at these same time points. All groups showed normal pathological tissues in the femoral nerves under optical microscopy. Under electron microscopy, histological abnormalities were observed only in Group E; none of the other groups exhibited pathological abnormalities. Quantitative analysis of the myelin sheath area revealed no significant difference in the axonal area, total area of the myelin sheath, or ratio of the total axonal area to the total area of the myelin sheath in all groups.

CONCLUSION
The lowest doses of dexmedetomidine (1 and 2 µg/mL) combined with 0.25% ropivacaine for continuous femoral nerve block resulted in no neurotoxic lesions, but the higher dose (3 µg/mL) resulted in neurotoxic lesions in this rabbit experimental model.

neurotoxicity
Dexmedetomidine
ropivacaine
femoral nerve block
demyelination
rabbit model


Future effects of climate and land-use change on terrestrial vertebrate community diversity under different scenarios.

Abstract: Land-use and climate change are among the greatest threats facing biodiversity, but understanding their combined effects has been hampered by modelling and data limitations, resulting in part from the very different scales at which land-use and climate processes operate. I combine two different modelling paradigms to predict the separate and combined (additive) effects of climate and land-use change on terrestrial vertebrate communities under four different scenarios. I predict that climate-change effects are likely to become a major pressure on biodiversity in the coming decades, probably matching or exceeding the effects of land-use change by 2070. The combined effects of both pressures are predicted to lead to an average cumulative loss of 37.9% of species from vertebrate communities under 'business as usual' (uncertainty ranging from 15.7% to 54.2%). Areas that are predicted to experience the effects of both pressures are concentrated in tropical grasslands and savannahs. The results have important implications for the conservation of biodiversity in future, and for the ability of biodiversity to support important ecosystem functions, upon which humans rely.

future
land-use change
scenarios
climate change
biodiversity
global


Transient disturbances in contextual fear memory induced by Aβ(25-35) in rats are accompanied by cholinergic dysfunction.

Abstract: Damage to the medial septum (MS) or disruption of the septo-hippocampal pathway is often considered as a basis for memory impairments, manifesting in the hippocampus-dependent behavioral paradigms. In the present study, we have examined the effects of intracerebroventricular administration of aggregated amyloid-β (25-35) (Aβ(25-35)) on contextual fear conditioning and the condition of cholinergic neurons in the MS using immunohistochemical detection of choline acetyltransferase (ChAT) and expression of the "cholinergic locus genes" (ChAT and vesicular acetylcholine transporter (VaChT) mRNA). A single injection of Aβ(25-35) induced transient moderate impairments in contextual fear conditioning accompaniedby a decrease in ChAT expression. However, the long-term decline in ChAT and VaChT expression was not associated with stable impairments in contextual fear memory. An Aβ(25-35)-induced progressive decrease in the number of ChAT expressing neurons in the MS was revealed, but no gross neuronal cell loss in the MS could be detected (as judged by the density of NeuN-immunoreactive cells). Thus, Aβ(25-35) induced a loss of the cholinergic phenotype of septal neurons without neuronal cell death in MS. The data give an additional support to the concept of early impairments in the synthesis of proteins related to the cholinergic system as an important mechanism in amyloid-induced neuronal damage.

Stepanichev|Mikhail|M| Lazareva|Natalia|N| Tukhbatova|Gulnur|G| Salozhin|Sergey|S| Gulyaeva|Natalia|N|

D050494:Vesicular Acetylcholine Transport Proteins

Medial septum
Contextual fear conditioning
Cholinergic neurons
Choline acetyltransferase
Vesicular acetylcholine transporter
Cholinergic phenotype
Amyloid-β (25–35)


Pediatric Acute Ischemic Stroke by Age-Group: A Systematic Review and Meta-Analysis of Published Studies and Hospitalization Records.

Abstract:
BACKGROUND
Although stroke is rare among the pediatric population, it is nevertheless associated with serious or life-threatening consequences. The etiologic factors of acute ischemic stroke (AIS) are likely to vary over the course of childhood development. The incidence rates of AIS, not previously systematically examined by pediatric age subgroup, could guide studies of its etiology.

OBJECTIVE
The aim of this study is to evaluate the incidence rate of AIS by age-group in the pediatric population (aged 0-17/18 years) and identify any common trends or sources of variability across different countries.

METHODS
Rates of pediatric AIS were collated from a systematic literature review of published studies globally (1983-2020) and hospitalization records from Europe and the USA (2015-2018). Records that were included in the analysis reported the code or description used for AIS diagnosis and age-specific data for children aged 0-17/18 years. AIS incidence rates were summarized by age-group, data source, country, and geographic region. A meta-analysis was conducted to assess the heterogeneity of AIS rates in neonates.

RESULTS
The pooled AIS incidence rate was 5.6 per 100,000 children across all records. When only records reporting the AIS incidence rates for children across the full age range (0-17/18 years) were analyzed, the pooled AIS incidence rate was 4.6 per 100,000 children and ranged from 7.0 per 100,000 (Germany) to 1.3 per 100,000 (Denmark). The highest pooled rates were observed in the 0-28-day age-group (24.6 per 100,000 live births), declining to the lowest rates in the 5-9-year age-group, and rising again in the 10-17/18-year age-group. AIS rates were the most heterogeneous in the 0-28-day age-group and across European countries. Significantly higher AIS rates in neonates were observed from hospital databases (35.9 per 100,000) than in the literature (19.4 per 100,000). AIS rates may be underestimated as pediatric AIS events are rare and challenging to diagnose, and limited age-specific data are available.

CONCLUSIONS
Incidence rates of pediatric AIS by age-groups followed a consistent overall pattern of a reverse J-shaped curve, with the highest rates in neonates, across predominantly European and North American countries. Further research is warranted to examine if this pattern is observed in other geographic regions and to identify AIS risk factors specific to different phases of childhood development.

Oleske|Denise M|DM|
Cheng|Xianbin|X|
Jeong|Anna|A|
Arndt|Thomas J|TJ|

Systematic review
Childhood stroke
Epidemiology
Neonatal stroke
Pediatric stroke


Upregulation of cystatin SN promotes hepatocellular carcinoma progression and predicts a poor prognosis.

Abstract: Cystatin SN, a specific cysteine protease inhibitor, is thought to be involved in various malignant tumors. Therefore, we evaluated the role of cystatin SN in hepatocellular carcinoma (HCC). Notably, cystatin SN was elevated in tumorous samples and cells. Moreover, overexpression of cystatin SN was correlated with tumor diameter and TNM stage. Cox multivariate analysis displayed that cystatin SN was an independent prognosis indicator and that high cystatin SN level was associated with a dismal prognosis. Moreover, cystatin SN enhancement facilitated the proliferation, migratory, and invasive potential of Huh7 and HCCLM3 cells, whereas cystatin SN knockdown caused the opposite effect. Cystatin SN also modulated the epithelial-mesenchymal transition progression through the PI3K/AKT pathway. In vivo cystatin SN promoted HCCLM3 cell growth and metastasis in xenograft mice model. Thus, cystatin SN was involved in HCC progression and could be a latent target for HCC treatment.

Cui|Yifeng|Y| Sun|Dan|D| Song|Ruipeng|R| Zhang|Shugeng|S| Liu|Xirui|X| Wang|Yan|Y| Meng|Fanzheng|F| Lan|Yaliang|Y| Han|Jihua|J| Pan|Shangha|S| Liang|Shuhang|S| Zhang|Bo|B| Guo|Hongrui|H| Liu|Yufeng|Y| Lu|Zhaoyang|Z|0000-0003-4588-2521 Liu|Lianxin|L|

D015972:Gene Expression Regulation, Neoplastic

cystatin SN
hepatocellular carcinoma
epithelial-mesenchymal transition
cell proliferation
prognostic marker


Time Courses of Inflammatory Markers after Aneurysmal Subarachnoid Hemorrhage and Their Possible Relevance for Future Studies.

Abstract:
Object
Aneurysmal subarachnoid hemorrhage triggers an intense inflammatory response, which is suspected to increase the risk for secondary complications such as delayed cerebral ischemia (DCI). However, to date, the monitoring of the inflammatory response to detect secondary complications such as DCI has not become part of the clinical routine diagnostic. Here, we aim to illustrate the time courses of inflammatory parameters after aneurysmal subarachnoid hemorrhage (aSAH) and discuss the problems of inflammatory parameters as biomarkers but also their possible relevance for deeper understanding of the pathophysiology after aSAH and sophisticated planning of future studies.

Materials and methods
In this prospective cohort study, 109 patients with aSAH were initially included, n = 28 patients had to be excluded. Serum and-if possible-cerebral spinal fluid samples (n = 48) were retrieved at days 1, 4, 7, 10, and 14 after aSAH. Samples were analyzed for leukocyte count and C-reactive protein (CRP) (serum samples only) as well as matrix metallopeptidase 9 (MMP9), intercellular adhesion molecule 1 (ICAM1), and leukemia inhibitory factor (LIF) [both serum and cerebrospinal fluid (CSF) samples]. Time courses of the inflammatory parameters were displayed and related to the occurrence of DCI.

Results
We illustrate the time courses of leukocyte count, CRP, MMP9, ICAM1, and LIF in patients' serum samples from the first until the 14th day after aSAH. Time courses of MMP9, ICAM1, and LIF in CSF samples are demonstrated. Furthermore, no significant difference was shown relating the time courses to the occurrence of DCI.

Conclusion
We estimate that the wide range of the measured values hampers their interpretation and usage as a biomarker. However, understanding the inflammatory response after aSAH and generating a multicenter database may facilitate further studies: realistic sample size calculations on the basis of a multicenter database will increase the quality and clinical relevance of the acquired results.

Höllig|Anke|A|
Stoffel-Wagner|Birgit|B|
Clusmann|Hans|H|
Veldeman|Michael|M|
Schubert|Gerrit A|GA|
Coburn|Mark|M|

subarachnoid hemorrhage
inflammatory response
delayed cerebral ischemia
early brain injury
observational research


Documenting and characterising gestational weight gain beliefs and experiences among Marshallese pregnant women in Arkansas: a protocol for a longitudinal mixed-methods study.

Abstract:
INTRODUCTION
Arkansas has the largest population of Marshallese Pacific Islanders residing in the continental USA. The Marshallese have higher rates of obesity, type 2 diabetes, pre-term births, low birthweight babies, infant mortality, and inadequate or no prenatal care. Despite the high rates of cardiometabolic and maternal and child health disparities among Marshallese, there are no studies documenting gestational weight gain or perceptions about gestational weight gain among the Marshallese population residing in the USA.

METHODS AND ANALYSIS
This paper describes the protocol of a mixed-methods concurrent triangulation longitudinal study designed to understand gestational weight gain in Marshallese women. The mixed-methods design collects qualitative and quantitative data during simultaneous data collection events, at both first and third trimester, and then augments that data with postpartum data abstraction. Quantitative and qualitative data will be analysed separately and then synthesised during the interpretation phase.

ETHICS AND DISSEMINATION
The study used a community engaged approach approved by the University of Arkansas for Medical Sciences Institutional Review Board (#228023). The research team will disseminate results to study participants, research stakeholders (clinics, faith-based organisations and community-based organisation), the broader Marshallese community and fellow researchers. Results will be disseminated to study participants through a one-page summary that show the aggregated research results using plain language and infographics.

Ayers|Britni L|BL|
Bogulski|Cari A|CA|
Haggard-Duff|Lauren|L|
Andres|Aline|A|
Børsheim|Elisabet|E|0000-0002-7842-0625
McElfish|Pearl A|PA|0000-0002-4033-6241

gynaecology
maternal medicine
protocols & guidelines
public health


Secure medical information sharing in cloud computing.

Abstract: Medical information sharing is one of the most attractive applications of cloud computing, where searchable encryption is a fascinating solution for securely and conveniently sharing medical data among different medical organizers. However, almost all previous works are designed in symmetric key encryption environment. The only works in public key encryption do not support keyword trapdoor security, have long ciphertext related to the number of receivers, do not support receiver revocation without re-encrypting, and do not preserve the membership of receivers. In this paper, we propose a searchable encryption supporting multiple receivers for medical information sharing based on bilinear maps in public key encryption environment. In the proposed protocol, data owner stores only one copy of his encrypted file and its corresponding encrypted keywords on cloud for multiple designated receivers. The keyword ciphertext is significantly shorter and its length is constant without relation to the number of designated receivers, i.e., for n receivers the ciphertext length is only twice the element length in the group. Only the owner knows that with whom his data is shared, and the access to his data is still under control after having been put on the cloud. We formally prove the security of keyword ciphertext based on the intractability of Bilinear Diffie-Hellman problem and the keyword trapdoor based on Decisional Diffie-Hellman problem.

Shao|Zhiyi|Z| Yang|Bo|B| Zhang|Wenzheng|W| Zhao|Yi|Y| Wu|Zhenqiang|Z| Miao|Meixia|M|

D016247:Information Storage and Retrieval

Medical information sharing
searchable encryption
trapdoor security
multiple receivers
ciphertext security


Disodium cromoglycate treatment reduces TH2 immune response and immunohistopathological features in a murine model of Eosinophilic Esophagitis.

Abstract: Eosinophilic esophagitis (EoE) is an emergent chronic disease of the esophagus. The immunopathological process in EoE is characterized by Th2 immune response and prominent eosinophilic influx, in response to common food allergens. The classical treatment consists of allergen elimination diet and systemic/topical corticosteroid therapy. Nevertheless, patients do not always comply to treatment, and the prolonged corticosteroid therapy can cause side effects, therefore, there is an immediate need for new therapeutic approach for EoE. Disodium cromoglicate (DSCG) is a substance broadly used in allergic asthma treatment, and a well-known mast cell activation stabilizer. However, its effect in EoE have not been evaluated yet. This study aimed to assess the effects of DSCG treatment in an EoE experimental model. Male Balb/C mice were subcutaneously sensitized for five days with OVA, and subsequently orally OVA-challenged, DSCG administration was performed between the OVA-challenges. DSCG treatment not only reduced eosinophilic and mast cell influx, as well as reduced fibrosis. In addition, tslp, GATA3, IL-5, FoxP3 and IL-10 mRNA expression were reduced in esophageal mucosa, associated with lower Th2 (CD3+CD4+GATA3+IL4+) and B cells (CD19+CD40+) number in peripheral lymphoid organs. In conclusion, the data demonstrate DSCG treatment was effective in reducing mast cell activation and Th2 immune response, important immunopathological EoE features. Therefore, the use of DSCG as an EoE treatment can be considered a promising therapeutic approach to treat this disease.

Disodium cromoglycate
Immune response
Eosinophilic esophagitis
Allergy
Inflammation


Retrotransverse foramen of the atlas: prevalence and bony variations.

Abstract:
PURPOSE
To analyze the prevalence of the retrotransverse foramen (RTF) and its bony variations.

METHODS
One hundred ten atlases of living adult subjects, 161 twentieth century dry adult cervical atlases and four dry adult cervical atlases from medieval skeletons were studied to detect the RTF and its abnormal bony variations. The 110 living adult subjects underwent a computed tomography study to detect the RTF.

RESULTS
In the in vivo sample (n = 110; 100%), the RTF was found in four (3.6%) atlases. It was bilateral in all cases, but three (2.7%) patients showed complete RTF and the other patient presented a complete RTF in the left transverse process and an unclosed RTF in the right transverse process. In addition, the RTF was observed in combination with an unclosed transverse foramen in two cases (1.8%). In the twentieth century skeletal sample (n = 206; 100%) the RTF was found in 15 (7.3%) C1 vertebrae. It was bilateral in three (1.5%) vertebrae and unilateral in another 12 (5.8%) vertebrae. In the medieval skeletal sample (n = 4; 100%) one cadaveric atlas (25%) presented a bilateral RTF with special bony characteristics which presented an unexpected spicula in the left RTF.

CONCLUSIONS
The RTF is a nonmetric variant of the atlas vertebra that can present non-degenerative and non-traumatic spiculae or it can be unclosed. In addition, it can be associated with the presence of unclosed transverse foramina.

Retrotransverse foramen
Atlas
Bony variations
Nonmetric variant
Cervical spine


Effect of diets containing earthworm powder and vermihumus on egg production, hatchability, blood parameters and immunity of Japanese breeder quails.

Abstract: The present study is aimed to evaluate the effects of different levels of earthworm (EW) powder and vermihumus (VH) on the growth performance, humoral immunity response, plasma constituents and reproductive performance of Japanese breeder quails. A total of 336 birds were assigned to seven treatments in a completely randomized design from day 30 to 90 of age. The dietary treatments were carried out, one without any addition of EW and VH, the second had a standard rate of VH at 0.8%, while a range of EW additions was supplied from 0%, 0.5%, 1%, 1.5%, 2% and 2.5%. The effects of treatments on body weight and mortality were not significant (p > .05). The highest feed intake was observed in birds fed the diets supplemented with 1% and 1.5% EW (p < .05). The highest titre of antibodies against influenza virus and sheep red blood cells belonged to the EW and VH treatments (p < .05). The antibody titre against Newcastle disease virus vaccine was not affected by the treatments. In general, the birds receiving EW and VH had the highest egg weight, egg production and egg mass weight (p < .05). Nonetheless, various levels of EW powder negatively affected hatchability and increased mortality and leg disorders (p < .05). The results showed that the levels of dietary 1% and 1.5% of EW powder gave the best growth and reproductive performance to birds respectively.

earthworm powder
vermihumus
hatchability
quail
feed intake
antibody


First Amazonian species of <i>Maracaynatum</i>, with comments on the genus (Opiliones: Laniatores: Samoidae).

Abstract: Among Opiliones, the family Samoidae Sørensen, 1886 is a group of small Laniatores with a wide tropical distribution. Neotropical samoids are distributed mainly in the Caribbean subregion, with species recorded from insular localities and the Venezuelan coastal range. Previously, for continental South America only three genera and just a few specimens of unidentified Samoidae have been recorded from Brazil. In this paper we describe Maracaynatum isadorae sp. nov., the first record of the genus for Brazil and the first samoid described for the Amazon biome. We also provide an emended diagnosis for the genus and a map with its distribution.

Colmenares|Pío A|PA|
Tourinho|Ana Lúcia|AL|

Opiliones, Caribbean, Central Amazon, harvestmen, Samooidea, taxonomy


Glutamate input in the dorsal raphe nucleus as a determinant of escalated aggression in male mice.

Abstract: Although the dorsal raphe nucleus (DRN) has long been linked to neural control of aggression, little is known about the regulatory influences of the DRN when an animal engages in either adaptive species-typical aggressive behavior or escalated aggression. Therefore it is important to explore which neurotransmitter inputs into the DRN determine the escalation of aggression in male mice. Previously, we observed that microinjection of the GABAB receptor agonist baclofen into the DRN escalates aggressive behavior in male mice. Here, we used a serotonin (5-HT) neuron-specific GABAB receptor knock-out mouse to demonstrate that baclofen acts on nonserotonergic neurons to escalate aggression. Intra-DRN baclofen administration increased glutamate release, but did not alter GABA release, within the DRN. Microinjection of l-glutamate into the DRN escalated dose-dependently attack bites toward an intruder. In vivo microdialysis showed that glutamate release increased in the DRN during an aggressive encounter, and the level of glutamate was further increased when the animal was engaged in escalated aggressive behavior after social instigation. Finally, 5-HT release was increased within the DRN and also in the medial prefrontal cortex when animals were provoked by social instigation, and during escalated aggression after social instigation, but this increase in 5-HT release was not observed when animals were engaged in species-typical aggression. In summary, glutamate input into the DRN is enhanced during escalated aggression, which causes a phasic increase of 5-HT release from the DRN 5-HT neurons.

Takahashi|Aki|A|
Lee|Ray X|RX|
Iwasato|Takuji|T|
Itohara|Shigeyoshi|S|
Arima|Hiroshi|H|
Bettler|Bernhard|B|
Miczek|Klaus A|KA|
Koide|Tsuyoshi|T|

glutamate
dorsal raphe nucleus
escalated aggression
species-typical aggressive behavior
GABAB receptor
serotonin (5-HT)


iTRAQ and RNA-Seq Analyses Provide New Insights into Regulation Mechanism of Symbiotic Germination of Dendrobium officinale Seeds (Orchidaceae).

Abstract: Mycorrhizal fungi colonize orchid seeds and induce germination. This so-called symbiotic germination is a critical developmental process in the lifecycle of all orchid species. However, the molecular changes that occur during orchid seed symbiotic germination remain largely unknown. To better understand the molecular mechanism of orchid seed germination, we performed a comparative transcriptomic and proteomic analysis of the Chinese traditional medicinal orchid Dendrobium officinale to explore the change in protein expression at the different developmental stages during asymbiotic and symbiotic germination and identify the key proteins that regulate the symbiotic germination of orchid seeds. Among 2256 identified plant proteins, 308 were differentially expressed across three developmental stages during asymbiotic and symbiotic germination, and 229 were differentially expressed during symbiotic germination compared to asymbiotic development. Of these, 32 proteins were coup-regulated at both the proteomic and transcriptomic levels during symbiotic germination compared to asymbiotic germination. Our results suggest that symbiotic germination of D. officinale seeds shares a common signaling pathway with asymbiotic germination during the early germination stage. However, compared to asymbiotic germination, fungal colonization of orchid seeds appears to induce higher and earlier expression of some key proteins involved in lipid and carbohydrate metabolism and thus improves the efficiency of utilization of stored substances present in the embryo. This study provides new insight into the molecular basis of orchid seed germination.

Chen|Juan|J|0000-0002-5407-8239
Liu|Si Si|SS|
Kohler|Annegret|A|
Yan|Bo|B|
Luo|Hong Mei|HM|
Chen|Xiao Mei|XM|
Guo|Shun Xing|SX|

D018507:Gene Expression Regulation, Developmental

Orchidaceae
seed germination
transcriptome
proteome
carbohydrate metabolism
defense reaction
mycorrhizal interaction


Accurate Prediction of Absorption Spectral Shifts of Proteorhodopsin Using a Fragment-Based Quantum Mechanical Method.

Abstract: Many experiments have been carried out to display different colors of Proteorhodopsin (PR) and its mutants, but the mechanism of color tuning of PR was not fully elucidated. In this study, we applied the Electrostatically Embedded Generalized Molecular Fractionation with Conjugate Caps (EE-GMFCC) method to the prediction of excitation energies of PRs. Excitation energies of 10 variants of Blue Proteorhodopsin (BPR-PR105Q) in residue 105GLN were calculated with the EE-GMFCC method at the TD-B3LYP/6-31G* level. The calculated results show good correlation with the experimental values of absorption wavelengths, although the experimental wavelength range among these systems is less than 50 nm. The ensemble-averaged electric fields along the polyene chain of retinal correlated well with EE-GMFCC calculated excitation energies for these 10 PRs, suggesting that electrostatic interactions from nearby residues are responsible for the color tuning. We also utilized the GMFCC method to decompose the excitation energy contribution per residue surrounding the chromophore. Our results show that residues ASP97 and ASP227 have the largest contribution to the absorption spectral shift of PR among the nearby residues of retinal. This work demonstrates that the EE-GMFCC method can be applied to accurately predict the absorption spectral shifts for biomacromolecules.

D056004:Molecular Dynamics Simulation
D011789:Quantum Theory
D025604:Rhodopsins, Microbial
D055672:Static Electricity

proteorhodopsin
electric field
absorption spectrum
fragmentation QM method


Interventions to Increase Male Attendance and Testing for Sexually Transmitted Infections at Publicly-Funded Family Planning Clinics.

Abstract:
PURPOSE
We assessed the impact of staff, clinic, and community interventions on male and female family planning client visit volume and sexually transmitted infection testing at a multisite community-based health care agency.

METHODS
Staff training, clinic environmental changes, in-reach/outreach, and efficiency assessments were implemented in two Family Health Center (San Diego, CA) family planning clinics during 2010-2012; five Family Health Center family planning programs were identified as comparison clinics. Client visit records were compared between preintervention (2007-2009) and postintervention (2010-2012) for both sets of clinics.

RESULTS
Of 7,826 male client visits during the time before intervention, most were for clients who were aged <30 years (50%), Hispanic (64%), and uninsured (81%). From preintervention to postintervention, intervention clinics significantly increased the number of male visits (4,004 to 8,385; Δ = +109%); for comparison clinics, male visits increased modestly (3,822 to 4,500; Δ = +18%). The proportion of male clinic visits where chlamydia testing was performed increased in intervention clinics (35% to 42%; p < .001) but decreased in comparison clinics (37% to 33%; p < .001). Subgroup analyses conducted among adolescent and young adult males yielded similar findings for male client volume and chlamydia testing. The number of female visits declined nearly 40% in both comparison (21,800 to 13,202; -39%) and intervention clinics (30,830 to 19,971; -35%) between preintervention and postintervention periods.

CONCLUSIONS
Multilevel interventions designed to increase male client volume and sexually transmitted infection testing services in family planning clinics succeeded without affecting female client volume or services.

Fine|David|D|
Warner|Lee|L|
Salomon|Sarah|S|
Johnson|David M|DM|

Sexually transmitted infections
Family planning
Chlamydia
Adolescents
Male reproductive health


Five new species and three new females of the genus  Endotricha Zeller from China (Lepidoptera, Pyralidae, Pyralinae).

Abstract: Five new species of the genus Endotricha Zeller are described from China: Endotricha dentiprocessasp. n., Endotricha unicolorsp. n., Endotricha shafferisp. n., Endotricha convexasp. n. and Endotricha whalleyisp. n. Females of three species are described for the first time: Endotricha hoenei Whalley, 1963, Endotricha luteogrisalis Hampson, 1896 and Endotricha simipunicea Wang & Li, 2005. Photographs of the adults and both male and female genitalia are provided.

new species
Endotricha
China
Lepidoptera
Pyralidae
Pyralinae
taxonomy


ADS-HCSpark: A scalable HaplotypeCaller leveraging adaptive data segmentation to accelerate variant calling on Spark.

Abstract:
BACKGROUND
The advance of next generation sequencing enables higher throughput with lower price, and as the basic of high-throughput sequencing data analysis, variant calling is widely used in disease research, clinical treatment and medicine research. However, current mainstream variant caller tools have a serious problem of computation bottlenecks, resulting in some long tail tasks when performing on large datasets. This prevents high scalability on clusters of multi-node and multi-core, and leads to long runtime and inefficient usage of computing resources. Thus, a high scalable tool which could run in distributed environment will be highly useful to accelerate variant calling on large scale genome data.

RESULTS
In this paper, we present ADS-HCSpark, a scalable tool for variant calling based on Apache Spark framework. ADS-HCSpark accelerates the process of variant calling by implementing the parallelization of mainstream GATK HaplotypeCaller algorithm on multi-core and multi-node. Aiming at solving the problem of computation skew in HaplotypeCaller, a parallel strategy of adaptive data segmentation is proposed and a variant calling algorithm based on adaptive data segmentation is implemented, which achieves good scalability on both single-node and multi-node. For the requirement that adjacent data blocks should have overlapped boundaries, Hadoop-BAM library is customized to implement partitioning BAM file into overlapped blocks, further improving the accuracy of variant calling.

CONCLUSIONS
ADS-HCSpark is a scalable tool to achieve variant calling based on Apache Spark framework, implementing the parallelization of GATK HaplotypeCaller algorithm. ADS-HCSpark is evaluated on our cluster and in the case of best performance that could be achieved in this experimental platform, ADS-HCSpark is 74% faster than GATK3.8 HaplotypeCaller on single-node experiments, 57% faster than GATK4.0 HaplotypeCallerSpark and 27% faster than SparkGA on multi-node experiments, with better scalability and the accuracy of over 99%. The source code of ADS-HCSpark is publicly available at https://github.com/SCUT-CCNL/ADS-HCSpark.git .

Adaptive data segmentation
Variant calling
Spark
Hadoop-BAM


Gene expression meta-analysis reveals the down-regulation of three GABA receptor subunits in the superior temporal gyrus of patients with schizophrenia.

Abstract: One of the main theories accounting for the underlying pathophysiology of schizophrenia posits alterations in GABAergic neurotransmission. While previous gene expression studies of postmortem brain samples typically report the down-regulation of GABA related genes in schizophrenia, the results are often inconsistent and not uniform across studies. We performed a systematic gene expression analysis of 22 GABA related genes in postmortem superior temporal gyrus (STG) samples of 19 elderly subjects with schizophrenia (mean age: 77) and 14 matched controls from the Icahn school of Medicine at Mount Sinai (MSSM) cohort. To test the validity and robustness of the resulting differentially expressed genes, we then conducted a meta-analysis of the MSSM and an independent dataset from the Stanley Consortium of 14 STG samples of relatively young subjects with schizophrenia (mean age: 44) and 15 matched controls. For the first time, the findings showed the down-regulation of three GABA-receptor subunits of type A, GABRA1, GABRA2 and GABRB3, in the STG samples of subjects with schizophrenia, in both the elderly and the relatively young patients. These findings, as well as previous results, lend weight to the notion of a common upstream pathology that alters GABAergic neurotransmission in schizophrenia. GABRA1, GABRA2 and GABRB3 down-regulation may contribute to the pathophysiology and clinical manifestations of schizophrenia through altered oscillation synchronization in the STG.

Frajman|Assaf|A| Maggio|Nicola|N| Muler|Inna|I| Haroutunian|Vahram|V| Katsel|Pavel|P| Yitzhaky|Assif|A| Weiser|Mark|M| Hertzberg|Libi|L|


Vitamin D inhibits development of liver fibrosis in an animal model but cannot ameliorate established cirrhosis.

Abstract: 1,25(OH)2D3, the active form of vitamin D, has an antiproliferative and antifibrotic effect on hepatic stellate cells. Our aim was to investigate the potential of 1,25(OH)2D3 to inhibit the development of liver fibrosis and to ameliorate established fibrosis in vivo. The antifibrotic effect of 1,25(OH)2D3 was investigated in a thioacetamide (TAA) model (as a preventive treatment and as a remedial treatment) and in a bile duct ligation model. In the preventive model, rats received simultaneously intraperitoneum injection of TAA and/or 1,25(OH)2D3 for 10 wk. In the remedial model, rats were treated with TAA for 10 wk and then received 1,25(OH)2D3 or saline for 8 wk. Fibrotic score was determined by Masson staining. Collagen I, α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase-1 (TIMP1), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) expression were measured by Western blot analysis and real-time PCR. Hypercalemia was detected by chemistry measurements. Preventive treatment of 1,25(OH)2D3 significantly suppressed liver fibrosis both macroscopically and microscopically and significantly lowered the fibrotic score of the TAA + 1,25(OH)2D3 group compared with the TAA group. 1,25(OH)2D3 significantly inhibited expression of PDGF and TGF-β by ∼50% and suppressed the expression of collagen Iα1, TIMP1, and α-SMA by approximately three-, two-, and threefold, respectively. In contrast, 1,25(OH)2D3 was inefficient in amelioration of established liver fibrosis. Administration of 1,25(OH)2D3 to bile duct ligation rats led to a high mortality rate probably caused by hypercalcemia. We conclude that 1,25(OH)2D3 may be considered as a potential preventive treatment in an in vivo model but failed to ameliorate established cirrhosis.

Abramovitch|Shirley|S| Sharvit|Efrat|E| Weisman|Yosef|Y| Bentov|Amir|A| Brazowski|Eli|E| Cohen|Gili|G| Volovelsky|Oded|O| Reif|Shimon|S|

vitamin D
liver
fibrosis
thioacetamide
collagen


Tumoral Expression of CD166 in Human Esophageal Squamous Cell Carcinoma: Implications for Cancer Progression and Prognosis.

Abstract: Accumulating data showed that cancer stem cells (CSCs) identified by cell surface markers contribute to the initiation, progression, and prognosis of human cancers. In this study, the expression of CSC candidates CD166, CD44, and Lgr5 in 65 cases of esophageal squamous cell carcinoma (ESCC) and 16 cases of control esophageal tissues were examined with immunohistochemistry (IHC). The correlation between tumoral expression levels of these CSC candidates and clinicopathological variables was analyzed. IHC results showed that the expression of CD166 in esophageal control tissues was completely negative, but it was in 87.69% (57/65) ESCC tissues. The expression of CD44 and Lgr5 did not differ between esophageal control tissues and ESCC tissues (p > 0.05). In addition, there were not correlations found among the expression levels of CD166, CD44, and Lgr5 in ESCC tissues. Clinicopathological analysis revealed that the tumoral expression level of CD166 correlated with lymph node involvement and TNM staging in patients with ESCC, and lower tumoral expression of CD44 was found in patients with advanced TNM staging. Kaplan-Meier survival curves suggested that expression level of CD166 appeared to have a negative impact on overall survival rate after surgery in patients with ESCC. Such impact was not found in other two CSC candidates. The authors therefore conclude that CD166 is a potential prognostic biomarker and correlates with advanced progression features in patients with ESCC.

Zhang|Xiaoshan|X| Yuan|Aping|A| Zhao|Xueru|X| Li|Zhenfeng|Z| Cui|Guanglin|G|

D015816:Cell Adhesion Molecules, Neuronal

D000077277:Esophageal Squamous Cell Carcinoma

esophageal squamous cell carcinoma
overall survival
stem cell marker


Multifunctional filtration membrane with anti-viscous-oils-fouling capacity and selective dyes adsorption ability for complex wastewater remediation.

Abstract: Multifunctional filtration membranes (MFMs), which can both effectively separate oil and selectively remove dyes from polluted aquatic system with robust anti-viscous-oil-fouling capacity, strong chemical/physical resistance, and long cycled stability, are highly required but still a challenge to be realized. Herein, a simple route has been demonstrated to address this challenge aforementioned by decorating both halloysite nanotubes (HNTs) and zwitterionic poly (sulfobetaine methyl methacrylate) (PSBMA) on the microporous polyvinylidene fluoride (PVDF) membrane surface via modified polydopamine (PDA) coating route. The as-prepared membrane exhibits super-hydrophilic/underwater super-oleophobic performance and high water permeation flux (32529 ± 278 L m-2 h-1 at 0.85 bar) to purify the diverse viscous oil-in-water emulsions from oily wastewater accompanying with good cycled stability (the recovery rate of permeate flux is close to 100% after 5 cycles). Moreover, the as-prepared MFM possesses not only strong chemical resistance under wide range of pH value (from 1 to 12) and high saline (NaCl: 10 wt%) environment, but also physical resistance against ultrasound bath for 30 min. Given the presence of HNTs, PDA, and PSBMA, our MFM shows enough active sites to adsorb the soluble dyes and metallic ions in wastewater. These excellent properties endow our MFM with great potential for the remediation of complex wastewater.

Zhou|Liang|L| Xiao|Guoqing|G| He|Yi|Y| Wu|Jingcheng|J| Shi|Heng|H| Zhong|Fei|F| Yin|Xiangying|X| Li|Zhenyu|Z| Chen|Jingyu|J|

Polydopamine
Antifouling
Contaminants adsorption
Emulsion separation
Zwitterionic polymer


Age- and sex-related mandibular dimensional changes: A radiomorphometric analysis on panoramic radiographs.

Abstract:
Introduction
Mandible undergoes age- and sex-related structural changes similar to other bones of the body. Thus, morphometric analysis of the mandible helps in age and sex determination.

Aim
To investigate the influence of age and sex on the mandible by measuring three parameters, i.e. gonial angle, ramus height and bigonial width.

Materials and Methods
A retrospective radiomorphometric analysis was conducted in the department of Oral Medicine and Radiology. A total of 300 panoramic radiographs (150 males and 150 females) equally distributed in six study groups according to the age were analysed. The measurements were performed using DIGORA 2.8 software for Windows. The acquired data was statistically analysed by one way ANOVA test and Student's t-test using SPSS (v. 19.0).

Results
Statistically significant differences according to age were found in gonial angle dimensions. Ramus height and bigonial width did not demonstrate statistically significant co-relation with age. According to sex, all the three study parameters showed statistically highly significant differences.

Conclusion
The morphometric analysis of the mandible is a useful tool for age estimation and sex determination.

Shah|Palak H|PH|
Venkatesh|Rashmi|R|
More|Chandramani B|CB|
Vaishnavee|V|V|

panoramic mandible Dental morphometry radiography


Isolation of membrane vesicles from prokaryotes: a technical and biological comparison reveals heterogeneity.

Abstract: Prokaryotes release membrane vesicles (MVs) with direct roles in disease pathogenesis. MVs are heterogeneous when isolated from bacterial cultures so Density Gradient Centrifugation (DGC) is valuable for separation of MV subgroups from contaminating material. Here we report the technical variability and natural biological heterogeneity seen between DGC preparations of MVs for Mycobacterium smegmatis and Escherichia coli and compare these DGC data with size exclusion chromatography (SEC) columns. Crude preparations of MVs, isolated from cultures by ultrafiltration and ultracentrifugation were separated by DGC with fractions manually collected as guided by visible bands. Yields of protein, RNA and endotoxin, protein banding and particle counts were analysed in these. DGC and SEC methods enabled separation of molecularly distinct MV populations from crude MVs. DGC banding profiles were unique for each of the two species of bacteria tested and further altered by changing culture conditions, for example with iron supplementation. SEC is time efficient, reproducible and cost effective method that may also allow partial LPS removal from Gram-negative bacterial MVs. In summary, both DGC and SEC are suitable for the separation of mixed populations of MVs and we advise trials of both, coupled with complete molecular and single vesicle characterisation prior to downstream experimentation.

Extracellular vesicles
microbe
nucleic acids
outer membrane vesicles
pathogen


Binding of human IgG to single-walled carbon nanotubes accelerated myeloperoxidase-mediated degradation in activated neutrophils.

Abstract: The binding of protein to carboxylated single-walled carbon nanotubes (SWCNTs) was believed to play an important role in the biological effects of nanotubes. However, the effects of protein-SWCNTs interactions on the oxidative degradation of nanotubes were not stressed enough. Here, we investigated the binding of human immunoglobulin G (IgG) to SWCNTs, and found that the preferred binding site was located in the Fc region of IgG. The hydrophobic and electrostatic interactions might be the crucial factors in stabilizing the binding of SWCNTs with IgG. Through the competitive binding of IgG and myeloperoxidase (MPO) to nanotube surfaces, the binding of IgG could impair MPO-induced SWCNTs biodegradation in vitro. However, both SWCNTs and IgG-SWCNTs were significantly degraded in zymosan-stimulated neutrophils, and the degradation degree was more for IgG-SWCNTs. These results suggest that the binding of IgG may be an important determinant for MPO-mediated SWCNTs biodegradation in activated human inflammatory cells.

Ding|Yun|Y| Tian|Rong|R| Yang|Zhen|Z| Chen|Jianfa|J| Lu|Naihao|N|

D057927:Hydrophobic and Hydrophilic Interactions

Human IgG
Single-walled carbon nanotubes
Neutrophils
Myeloperoxidase
Biodegradation


Comparison between Primary and Secondary Tracheoesophageal Puncture Prosthesis: A Systematic Review.

Abstract:
INTRODUCTION
Since the introduction of tracheoesophageal puncture (TEP) and placement of voice prosthesis, this has become the method of choice to achieve speech rehabilitation after total laryngectomy.

OBJECTIVE
To compare the complications and success in speech rehabilitation of patients undergoing rehabilitation after primary and secondary TEP (TEP1 and TEP2) through a systematic review.

METHODS
The literature survey included research in MedLine, Scielo, Lilacs, Cochrane and Websco until June 2016.

RESULTS
The rate of leakage around the prosthesis was higher in TEP1 (22.5 vs. 6.9%, p = 0.03). There were higher rates of wound infection (9.1 vs. 3.9%) and tracheal stenosis (8.5 vs. 4.5%) in the TEP1 group compared to TEP2, however with no statistical significance. The evaluation of speech quality was not possible due to the heterogeneity of the studies.

CONCLUSION
There is a reduction in the risk of leakage around the prosthesis among TEP2 patients.

Barauna Neto|José Carlos|JC|
Dedivitis|Rogério Aparecido|RA|
Aires|Felipe Toyama|FT|
Pfann|Robert Zasawadzki|RZ|
Matos|Leandro Luongo|LL|
Cernea|Claudio Roberto|CR|

Systematic review
Rehabilitation
Laryngectomy
Complications
Carcinoma
Laryngeal prosthesis
Meta-analysis
Squamous cell


Lung cancer development in the patient with granulomatosis with polyangiitis during long term treatment with cyclophosphamide: first documented case.

Abstract: A 65-year-old man was diagnosed with granulomatosis with polyangiitis (GPA) at the age of 47, when cytoplasmic anti-neutrophil cytoplasmic antibody (C-ANCA) serology was positive, and he had multiple nodular shadows in both lungs. He had been treated with prednisolone, cyclophosphamide (CPA) and plasma exchange. At the age of 64, a nodular shadow was newly detected in the right lower lung field and serum tumour marker increased. Subsequent positron emission tomography/computed tomography scan demonstrated accumulations of fluorodexyglucose (FDG) in the same area, mediastinum lymph nodes, thoracic wall, right iliac bone, and right retroperitoneum. The diagnosis of squamous cell lung cancer cT2bN2M1b Stage4 was made with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). There are no reports of cases that lung cancer has developed with GPA during the long-term treatment with CPA. We suggest that in such patients, the differential diagnosis should include not only the relapse of GPA, but also the rare possibility of development of carcinomas.

Toriyama|Midori|M|0000-0002-3852-5449 Tagaya|Etsuko|E| Yamamoto|Tomoko|T| Kondo|Mitsuko|M| Nagashima|Yoji|Y| Tamaoki|Jun|J|

lung cancer
granulomatosis with polyangiitis
cyclophosphamide
ANCA‐associated diseases


Injury incidence in semi-professional football claims for increased need of injury prevention in elite junior football.

Abstract:
PURPOSE
Injuries are a common occurrence in football. Sufficient epidemiological data are available in professional football but not in salaried semi-professional football. This study investigates the injury incidence at different levels of semi-professional football with focus on junior football.

METHODS
The data were based on injury reports provided by players and medical staff over the 2015-2016 season, which corresponded to the consensus statement for data samples in football. This study investigated the injury incidence and prevalence of five skill levels of semi-professional football (the fourth to the seventh league and elite junior football).

RESULTS
1130 players had sustained 2630 injuries over the 2015-2016 season. The overall injury incidence was 9.7 per 1000 h football exposure; prevalence with at least one injury was 79%. The highest overall injury incidence in elite junior football was 10.4 in 1000 h football exposure. The fifth league had the lowest incidence with 9.0 in 1000 h football (p < 0.05). Traumatic injuries most often occurred in the fourth league (3.9 in 1000 h football). The body areas most affected by traumatic injury were knees, ankles and thighs. Elite junior players had a significantly higher incidence of overuse complaints (7.4 in 1000 h football) than the fourth league (5.4, p = 0.005). The body areas most affected by overuse complaints were the lower back, thigh and groin. No differences were found between the different positions on field.

CONCLUSIONS
Salaried semi-professional football involves a high overall injury incidence. The highest incidence, particularly of overuse injuries, was seen in elite junior football. These findings should be incorporated in specific injury prevention training or screenings beginning in junior football. Level of evidence II.

Loose|Oliver|O| Fellner|Birgit|B| Lehmann|Jennifer|J| Achenbach|Leonard|L| Krutsch|Volker|V| Gerling|Stephan|S| Jansen|Petra|P| Angele|Peter|P| Nerlich|Michael|M| Krutsch|Werner|W|

Injury
Incidence
Prevention
Salary
Elite football
Soccer


Comparison of the modified shuttle walk test and cardiopulmonary exercise test in sarcoidosis.

Abstract:
BACKGROUND AND OBJECTIVE
Dyspnoea and exercise intolerance are common in sarcoidosis and are often poorly correlated with resting lung function. Measurement of peak exercise capacity is likely to be helpful in assessing and monitoring disease. The aim of this study was to compare the modified shuttle walk test (MSWT) to cardiopulmonary exercise test (CPET) as a measure of peak exercise capacity in sarcoidosis.

METHODS
Thirty-three (17 male, mean age 48 years) patients with sarcoidosis completed a standardized exponential exercise protocol cycle ergometer CPET and a single corridor MSWT in random order.

RESULTS
Subjects has a mean forced expiratory volume in 1 s (FEV1) 2.4 L (75.7%predicted), forced vital capacity (FVC) 3.43 L (88.7%predicted) and diffusing capacity for carbon monoxide (DLCO) 20.3 mL/min/mm Hg (71.4%predicted). There was a strong correlation between MSWT distance and peak oxygen uptake (VO2) during CPET (r = 0.87; P < 0.0001), and between maximum heart rate during MSWT and CPET (r = 0.82; P < 0.0001). There was a moderate correlation between FEV1 , FVC and DLCO with MSWT distance (r = 0.55, r = 0.61, r = 0.61, respectively; all P < 0.001) and with peak VO2 (r = 0.62, r = 0.63, r = 0.62, respectively; all P < 0.0001).

CONCLUSIONS
Peak VO2 achieved during CPET strongly correlated with MSWT distance. MSWT is a measure of peak exercise capacity in sarcoidosis that does not require equipment and can be readily available in the clinic.

de Boer|Sally|S|
Kolbe|John|J|
Wilsher|Margaret L|ML|

modified shuttle walk test
cardiopulmonary exercise test
sarcoidosis
bicycle ergometry test
pulmonary function


Association of metabolic syndrome with serum fibroblast growth factor 21 in kidney transplanted patients.

Abstract:
INTRODUCTION
Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple beneficial effects on glucose and lipid homeostasis and insulin sensitivity.

OBJECTIVES
The aim of this study was to investigate the relation between the serum level of FGF21 with and metabolic syndrome (MS) in kidney transplant recipients.

PATIENTS AND METHODS
We performed a cross-sectional study on 86 stable renal transplant recipients to detect possible relation between serum FGF21 level and MS during October 2014 and Mach 2015. Patients with past history of diabetes mellitus were excluded.

RESULTS
There were 43 patients in each group with and without MS. Totally, they were 52 (60.5%) male and 34 (39.5%) female. The mean age of the MS group was significantly higher than that of non-MS group. There was not significant difference between mean serum creatinine level and glomerular filtration rate (GFR) between two groups (P > 0.05). The MS patients had higher weight and body mass index (BMI) (P < 0.05). The prevalence of BMI >25 kg/m(2) in MS group was 25 (58.8%) versus non-MS group that only 10 (23.3%) had this condition (P < 0.05). The mean of FGF21 level in MS and non-MS groups was 1.23 ± 0.67 ng/l and 1.18 ± 0.71 ng/l, respectively (P > 0.05). There was not significant difference of serum FGF21 level between MS and non-MS patients (P > 0.05).

CONCLUSION
While the elevated serum FGF21 level was found in subjects with insulin resistant states, however, this study revealed that serum FGF21 levels were not significantly increased in renal transplanted recipients with MS as compared with non-MS group.

Bagheri|Leila|L|
Hami|Maryam|M|
Mojahedi|Mohammad-Javad|MJ|
Ghorban Sabbagh|Mahin|M|
Ayatollahi|Hosein|H|

Metabolic syndrome
Kidney transplantation
FGF21


The growing importance of lesion volume as a prognostic factor in patients with multiple brain metastases treated with stereotactic radiosurgery.

Abstract: Stereotactic Radiosurgery (SRS) is considered standard of care for patients with 1-3 brain metastases (BM). Recent observational studies have shown equivalent OS in patients with 5+ BM compared to those with 2-4, suggesting SRS alone may be appropriate in these patients. We aim to review outcomes of patients treated with SRS with 2-4 versus 5+ BM. This analysis included consecutive patients from 1994 to 2015 treated with SRS. Of 1017 patients, we excluded patients with a single BM and patients without adequate survival data, resulting in 391 patients. All risk factors were entered into univariate analysis using Cox proportional hazards model, and significant factors were entered into multivariate analysis (MVA). We additionally analyzed outcomes after excluding patients with prior surgery or whole-brain radiotherapy (WBRT). Median follow-up was 7.1 months. Median KPS was 90, mean age was 59, and most common histologies were melanoma and lung. Median tumor volume was 3.41 cc. Patients with 2-4 BM had a median OS of 8.1 months compared to 6.2 months for those with 5+ BM (P = 0.0136). On MVA, tumor volume, KPS, and histology remained significant for OS, whereas lesion number did not. Similar results were found when excluding patients with prior surgery or WBRT. Rather than lesion number, the strongest prognostic factors for patients undergoing SRS were tumor volume >10 cc, KPS, and histology. BM number may therefore not be the most important criterion for candidacy for SRS. Patients with 5 or more BM should be considered for SRS.

Routman|David M|DM|0000-0002-2768-003X
Bian|Shelly X|SX|
Diao|Kevin|K|0000-0002-7092-6162
Liu|Jonathan L|JL|
Yu|Cheng|C|
Ye|Jason|J|
Zada|Gabriel|G|
Chang|Eric L|EL|

Brain metastases
stereotactic radiosurgery
tumor volume
lesion number
whole-brain radiation therapy


Substantial Progress Yet Significant Opportunity for Improvement in Stroke Care in China.

Abstract:
BACKGROUND AND PURPOSE
Stroke is a leading cause of death in China. Yet the adherence to guideline-recommended ischemic stroke performance metrics in the past decade has been previously shown to be suboptimal. Since then, several nationwide stroke quality management initiatives have been conducted in China. We sought to determine whether adherence had improved since then.

METHODS
Data were obtained from the 2 phases of China National Stroke Registries, which included 131 hospitals (12 173 patients with acute ischemic stroke) in China National Stroke Registries phase 1 from 2007 to 2008 versus 219 hospitals (19 604 patients) in China National Stroke Registries phase 2 from 2012 to 2013. Multiple regression models were developed to evaluate the difference in adherence to performance measure between the 2 study periods.

RESULTS
The overall quality of care has improved over time, as reflected by the higher composite score of 0.76 in 2012 to 2013 versus 0.63 in 2007 to 2008. Nine of 13 individual performance metrics improved. However, there were no significant improvements in the rates of intravenous thrombolytic therapy and anticoagulation for atrial fibrillation. After multivariate analysis, there remained a significant 1.17-fold (95% confidence interval, 1.14-1.21) increase in the odds of delivering evidence-based performance metrics in the more recent time periods versus older data. The performance metrics with the most significantly increased odds included stroke education, dysphagia screening, smoking cessation, and antithrombotics at discharge.

CONCLUSIONS
Adherence to stroke performance metrics has increased over time, but significant opportunities remain for further improvement. Continuous stroke quality improvement program should be developed as a national priority in China.

Li|Zixiao|Z|
Wang|Chunjuan|C|
Zhao|Xingquan|X|
Liu|Liping|L|
Wang|Chunxue|C|
Li|Hao|H|
Shen|Haipeng|H|
Liang|Li|L|
Bettger|Janet|J|
Yang|Qing|Q|
Wang|David|D|
Wang|Anxin|A|
Pan|Yuesong|Y|
Jiang|Yong|Y|
Yang|Xiaomeng|X|
Zhang|Changqing|C|
Fonarow|Gregg C|GC|
Schwamm|Lee H|LH|
Hu|Bo|B|
Peterson|Eric D|ED|
Xian|Ying|Y|
Wang|Yilong|Y|
Wang|Yongjun|Y|
|||

stroke
China
registries
hospitals
quality improvement