Τετάρτη 7 Ιουνίου 2017

Cellular response in the tick feeding site in crossbred cattle artificially infested by Rhipicephalus microplus

Abstract

Ticks and tick-borne diseases are of global importance and can cause serious economic losses to cattle-raising businesses. However, only few attempts have been made to describe the relationships between various cellular immune components and tick counts of, and therefore resistance to, Rhipicephalus microplus. The present study evaluated the late inflammatory cellular response and dermal dendritic cells at the attachment site in naturally presensitized bovines, artificially infested by R. microplus ticks. Twenty-two crossbred (Holstein × Gir) male experimental cattle were artificially infested with approximately 10,000 larvae of R. microplus. Parasitic infestation was determined by counting the engorged female ticks (4.5–8.0 mm in diameter) at the 21st day after artificial infestation. Biopsies (6 mm) were taken prior to the infestation and along with the tick count from the right pinna of each animal, and examined with histological techniques and immunohistochemistry using S100 protein. Inflammatory cell counts were conducted in the sections stained with the May-Grünwald Giemsa technique, and immunostained dermal dendritic cells were evaluated and classified in scores ranging from 0 to 4. An average of 39.2 ticks per animal was found. Eosinophils (47.8%) constituted the major portion of the cellular infiltrate, followed by mononuclear cells (28.3%), neutrophils (14.4%), and basophils (0% to approximately 2%). The dendritic cell count shows a considerable population in the dermis, with pre- and post-infestation mean scores of 1.54 and 1.89, respectively; these scores were not significantly different. Our results pointed out the importance of the cellular response in the cattle resistance to ticks.



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Lung involvement in “stable” undifferentiated connective tissue diseases: a rheumatology perspective

Abstract

Previous studies of the occurrence of interstitial lung disease (ILD) in undifferentiated connective tissue diseases (UCTD) were conducted in patients admitted to Respiratory Medicine Units. The aim of the present prospective study was to investigate lung involvement in UCTD patients admitted to a Rheumatology Unit. Eighty-one consecutive UCTD patients were enrolled in the study. Each patient underwent history and physical examination, routine laboratory investigations, antinuclear antibody (ANA) profiling, B-mode echocardiography, and lung function study according to previously reported methods. Lung high resolution computed tomography (HRCT) was performed in patients who provided informed consent. Six patients (7.4%) had a history of grade II dyspnea. Three of them had a DLCO ranging from 42 to 55% of the predicted value; and a HRCT-documented ILD with a non-specific interstitial pneumonia (NSIP) pattern. Symptoms in the other three patients were due to cardiac disease. None of the 75 asymptomatic patients, had relevant findings at physical examination, 26/75 had a DLCO <80% (<70% in 10 cases). Of these, 3 of the 30 patients who underwent lung HRCT were affected by NSIP-ILD. Six of the 81 enrolled were affected by ILD, which was symptomatic in three patients. A higher percentage of patients had a reduced DLCO. The latter finding may reflect a preradiographic ILD or a preechocardiographic pulmonary vascular disease.



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Lung involvement in “stable” undifferentiated connective tissue diseases: a rheumatology perspective

Abstract

Previous studies of the occurrence of interstitial lung disease (ILD) in undifferentiated connective tissue diseases (UCTD) were conducted in patients admitted to Respiratory Medicine Units. The aim of the present prospective study was to investigate lung involvement in UCTD patients admitted to a Rheumatology Unit. Eighty-one consecutive UCTD patients were enrolled in the study. Each patient underwent history and physical examination, routine laboratory investigations, antinuclear antibody (ANA) profiling, B-mode echocardiography, and lung function study according to previously reported methods. Lung high resolution computed tomography (HRCT) was performed in patients who provided informed consent. Six patients (7.4%) had a history of grade II dyspnea. Three of them had a DLCO ranging from 42 to 55% of the predicted value; and a HRCT-documented ILD with a non-specific interstitial pneumonia (NSIP) pattern. Symptoms in the other three patients were due to cardiac disease. None of the 75 asymptomatic patients, had relevant findings at physical examination, 26/75 had a DLCO <80% (<70% in 10 cases). Of these, 3 of the 30 patients who underwent lung HRCT were affected by NSIP-ILD. Six of the 81 enrolled were affected by ILD, which was symptomatic in three patients. A higher percentage of patients had a reduced DLCO. The latter finding may reflect a preradiographic ILD or a preechocardiographic pulmonary vascular disease.



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Pharmacologic Considerations for Pediatric Sedation and Anesthesia Outside the Operating Room: A Review for Anesthesia and Non-Anesthesia Providers

Abstract

Understanding the pharmacologic options for pediatric sedation outside the operating room will allow practitioners to formulate an ideal anesthetic plan, allaying anxiety and achieving optimal immobilization while ensuring rapid and efficient recovery. The authors identified relevant medical literature by searching PubMed, MEDLINE, Embase, Scopus, Web of Science, and Google Scholar databases for English language publications covering a period from 1984 to 2017. Search terms included pediatric anesthesia, pediatric sedation, non-operating room sedation, sedation safety, and pharmacology. As a narrative review of common sedation/anesthesia options, the authors elected to focus on studies, reviews, and case reports that show clinical relevance to modern day sedation/anesthesia practice. A variety of pharmacologic agents are available for sedation/anesthesia in pediatrics, including midazolam, fentanyl, ketamine, dexmedetomidine, etomidate, and propofol. Dosing ranges reported are a combination of what is discussed in the reviewed literature and text books along with personal recommendations based on our own practice. Several reports reveal that ketofol (a combination of ketamine and propofol) is quite popular for short, painful procedures. Fospropofol is a newer-generation propofol that may confer advantages over regular propofol. Remimazolam combines the pharmacologic effects of remifentanil and midazolam. A variety of etomidate derivatives such as methoxycarbonyl-etomidate, carboetomidate, methoxycarbonyl-carboetomidate, and cyclopropyl-methoxycarbonyl metomidate are in development stages. The use of nitrous oxide as a mild sedative, analgesic, and amnestic agent is gaining popularity, especially in the ambulatory setting. Utilizing a dedicated and experienced team to provide sedation enhances safety. Furthermore, limiting sedation plans to single-agent pharmacy appears to be safer than using multi-agent plans.



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Brain reward responses to food stimuli among female monozygotic twins discordant for BMI

Abstract

Obese individuals are characterized by altered brain reward responses to food. Despite the latest discovery of obesity-associated genes, the contribution of environmental and genetic factors to brain reward responsiveness to food remains largely unclear. Sixteen female monozygotic twin pairs with a mean BMI discordance of 3.96 ± 2.1 kg/m2 were selected from the Netherlands Twin Register to undergo functional MRI scanning while watching high- and low-calorie food and non-food pictures and during the anticipation and receipt of chocolate milk. In addition, appetite ratings, eating behavior and food intake were assessed using visual analog scales, validated questionnaires and an ad libitum lunch. In the overall group, visual and taste stimuli elicited significant activation in regions of interest (ROIs) implicated in reward, i.e. amygdala, insula, striatum and orbitofrontal cortex. However, when comparing leaner and heavier co-twins no statistically significant differences in ROI-activations were observed after family wise error correction. Heavier versus leaner co-twins reported higher feelings of hunger (P = 0.02), cravings for sweet food (P = 0.04), body dissatisfaction (P < 0.05) and a trend towards more emotional eating (P = 0.1), whereas caloric intake was not significantly different between groups (P = 0.3). Our results suggest that inherited rather than environmental factors are largely responsible for the obesity-related altered brain responsiveness to food. Future studies should elucidate the genetic variants underlying the susceptibility to reward dysfunction and obesity.

Clinical Trial Registration Number: NCT02025595.



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The prevalence of incidental findings on computed tomography of the abdomen/pelvis in pediatric trauma patients

Abstract

Purpose

Computed tomography scans of the abdomen/pelvis (CTAP) in the adult population may reveal findings unrelated to the injury, such as a mass; the occurrence of incidental findings in pediatric patients remains unknown. This study aims to determine the percentage of pediatric trauma patients with incidental findings.

Methods

Data regarding consecutive 250 patients who underwent CTAP during their evaluation were retrieved from our level 1 pediatric trauma center trauma registry. Interpretations were reviewed for mention of incidental findings. Records for patients with incidental findings were examined to determine what further evaluation occurred.

Results

Nine patients were excluded due to incomplete records. Of the remaining 241 patients, 114 incidental findings were identified among 86 (35.7%) patients. There were 47 clinically significant incidental findings, occurring in 41 (17%) patients. Seven patients (8.1%) had further workup of their findings; Three (3.5%) went on to have an operation (two patients with ureteropelvic junction obstruction and one with high-riding testicle). No potential tumors were found in this population. Incidental findings were mentioned in 25.5% of discharge summaries.

Conclusions

Pediatric trauma CTAP reveals incidental findings at a lower rate than in their adult counterparts. Documentation of findings should be improved for optimal care of the injured child.



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BMI May Be the Risk Factor for Arytenoid Dislocation Caused by Endotracheal Intubation: A Retrospective Case-Control Study

This study aimed to investigate the risk factors for postoperative arytenoid dislocation caused by endotracheal intubation.

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Evolution of intrinsic disorder in eukaryotic proteins

Abstract

Conformational flexibility conferred though regions of intrinsic structural disorder allows proteins to behave as dynamic molecules. While it is well-known that intrinsically disordered regions can undergo disorder-to-order transitions in real-time as part of their function, we also are beginning to learn more about the dynamics of disorder-to-order transitions along evolutionary time-scales. Intrinsically disordered regions endow proteins with functional promiscuity, which is further enhanced by the ability of some of these regions to undergo real-time disorder-to-order transitions. Disorder content affects gene retention after whole genome duplication, but it is not necessarily conserved. Altered patterns of disorder resulting from evolutionary disorder-to-order transitions indicate that disorder evolves to modify function through refining stability, regulation, and interactions. Here, we review the evolution of intrinsically disordered regions in eukaryotic proteins. We discuss the interplay between secondary structure and disorder on evolutionary time-scales, the importance of disorder for eukaryotic proteome expansion and functional divergence, and the evolutionary dynamics of disorder.



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Characterization of Douglas-fir grown in Portugal: heartwood, sapwood, bark, ring width and taper

Abstract

Douglas-fir (Pseudotsuga menziesii) is one of the best timber conifers providing long sawnwood components. Original from North America, it has been planted in Europe on approximately 550 thousand ha. Twenty Douglas-fir trees growing in two sites in Portugal were studied regarding ring analysis, heartwood, sapwood and bark development, and taper. The radial growth rate was 7.1 and 6.6 mm year−1 at stem base for 45- and 50-year-old trees, respectively, in the two sites. Initial growth rate was slower, increasing until about 20 years and decreasing afterwards. Heartwood proportion represented on average 49% of the cross section in the lower part of the stem and decreased upwards. Heartwood formation was estimated to start at a cambial age of 8–9 years and increasing by 0.7–0.9 rings year−1. Sapwood width was on average 75 mm at stem base, decreasing upwards. Bark was 26–27 mm thick at stem base, where it represented 15% of the cross-sectional area and decreased to 3–5 mm at the top. Stemwood and heartwood tapers were on average 15 mm m−1 in the lower stem part and 21 and 18 mm m−1, respectively, in the upper part. Douglas-fir showed a good potential for the mountain areas of Portugal, and under the silvicultural conditions of both stands the trees presented ring homogeneity, small conicity and low taper suitable for long wood components.



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Impact of hemodynamic goal-directed resuscitation on mortality in adult critically ill patients: a systematic review and meta-analysis

Abstract

The effect of hemodynamic optimization in critically ill patients has been challenged in recent years. The aim of the meta-analysis was to evaluate if a protocolized intervention based on the result of hemodynamic monitoring reduces mortality in critically ill patients. We performed a systematic review and meta-analysis according to the Cochrane Handbook for Systematic Reviews of Interventions. The study was registered in the PROSPERO database (CRD42015019539). Randomized controlled trials published in English, reporting studies on adult patients treated in an intensive care unit, emergency department or equivalent level of care were included. Interventions had to be protocolized and based on results from hemodynamic measurements, defined as cardiac output, stroke volume, stroke volume variation, oxygen delivery, and central venous-or mixed venous oxygenation. The control group had to be treated without any structured intervention based on the parameters mentioned above, however, monitoring by central venous pressure measurements was allowed. Out of 998 screened papers, thirteen met the inclusion criteria. A total of 3323 patients were enrolled in the six trials with low risk of bias (ROB). The mortality was 22.4% (374/1671 patients) in the intervention group and 22.9% (378/1652 patients) in the control group, OR 0.94 with a 95% CI of 0.73–1.22. We found no statistically significant reduction in mortality from hemodynamic optimization using hemodynamic monitoring in combination with a structured algorithm. The number of high quality trials evaluating the effect of protocolized hemodynamic management directed towards a meaningful treatment goal in critically ill patients in comparison to standard of care treatment is too low to prove or exclude a reduction in mortality.



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Trump businesses got money meant for children's cancer research: report - WPXI Pittsburgh


WPXI Pittsburgh

Trump businesses got money meant for children's cancer research: report
WPXI Pittsburgh
Through Eric Trump's foundation, which supports child cancer research, the president's Donald J. Trump Foundation appeared to have funneled $100,000 worth of charity donations into the Trump family's coffers, according to a report from Forbes magazine.
How Donald Trump Shifted Kids-Cancer Charity Money Into His BusinessForbes

all 183 news articles »


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Distinct expression profile of HCMV encoded miRNAs in plasma from oral lichen planus patients

Oral lichen planus (OLP) is a T cell-mediated autoimmune disease. The aetiology and molecular mechanisms of OLP remain unclear. Human cytomegalovirus (HCMV) infection is a causal factor in the development of v...

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Examining clinical similarities between myalgic encephalomyelitis/chronic fatigue syndrome and d-lactic acidosis: a systematic review

The pursuit for clarity in diagnostic and treatment pathways for the complex, chronic condition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) continues. This systematic review raises a novel q...

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Betaine promotes cell differentiation of human osteoblasts in primary culture

Betaine (BET), a component of many foods, is an essential osmolyte and a source of methyl groups; it also shows an antioxidant activity. Moreover, BET stimulates muscle differentiation via insulin like growth ...

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State of play and clinical prospects of antibody gene transfer

Recombinant monoclonal antibodies (mAbs) are one of today’s most successful therapeutic classes in inflammatory diseases and oncology. A wider accessibility and implementation, however, is hampered by the high...

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Exercise in claudicants increase or decrease walking ability and the response relates to mitochondrial function

Exercise of patients with intermittent claudication improves walking performance. Exercise does not usually increase blood flow, but seems to increase muscle mitochondrial enzyme activities. Although exercise ...

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Risk factors for cut-out failure of Gamma3 nails in treating unstable intertrochanteric fractures: An analysis of 176 patients

Cut-out failure is one of the most common complications in the Gamma3 nail fixation system. The purpose of this retrospective study was to determine pre-operative or intra-operative risk factors for cut-out failure of lag screws in unstable, intertrochanteric fractures fixed with short Gamma3 nails.

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Vitamin D and jaundiced newborns

We read the currently published article entitled “Comparison between maternal and neonatal serum vitamin D levels in term jaundiced and non-jaundiced cases”1 with interest. Dr. Aletayeb and colleagues conducted a case-control study to evaluate the serum vitamin D levels of mothers and their term newborns and investigate the relationship between these serum vitamin D levels and occurrence of jaundice.1 The authors found that the mean vitamin D levels were significantly lower in the jaundiced newborns than those in the nonjaundiced controls (84.4 vs.

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Nasogastric tube placement with video-guided laryngoscope: A manikin simulator study

This study aimed to investigate video-guided laryngoscopy for nasogastric tube placement.

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Outcomes of 23-gauge transconjunctival sutureless vitrectomy for acute postoperative endophthalmitis

To report our 3-year experience of 23-gauge transconjunctival sutureless vitrectomy (TSV) for acute postoperative endophthalmitis at a tertiary referral center in southern Taiwan.

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Routine echocardiography in patients with myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is an autosomal-dominant disease. One third of DM1 patients die suddenly, most of them due to the heart conduction abnormalities and arrhythmias. The aim of this study was to analyze echocardiographic findings in a large cohort of DM1 patients.

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Lithium Chloride Facilitates Autophagy Following Spinal Cord Injury via ERK-dependent Pathway

Abstract

Spinal cord injury (SCI) is one major cause of death and results in long-term disability even in the most productive periods of human lives with few efficacious drugs. Autophagy is a potential therapeutic target for SCI. In the present study, we examined the role of lithium in functional recovery in the rat model of SCI and explored the related mechanism. Locomotion tests were employed to assess the functional recovery after SCI, Western blotting and RT-PCT to determine the level of p-ERK and LC3-II as well as p62, immunofluorescence imaging to localize LC3 and p62. Here, we found that both the expression of LC3-II and p62 were increased after SCI. However, lithium chloride enhanced the level of LC3-II while abrogated the abundance of p62. Furthermore, lithium treatment facilitated ERK activation in vivo, and inhibition of MEK/ERK signaling pathway suppressed lithium-evoked autophagy flux. Taken together, our results illustrated that lithium facilitated functional recovery by enhancing autophagy flux.



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Eternal Night: Ecosocialism and the Specific Ecological Threat of Trumpism

Environmental Justice , Vol. 0, No. 0.


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The Implications of Local Perceptions, Knowledge, and Adaptive Strategies for Adaptation Planning in Coastal Communities of Zanzibar

Environmental Justice , Vol. 0, No. 0.


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Taking Lessons from Refugees in Europe to Prepare for Climate Migrants and Exiles

Environmental Justice , Vol. 0, No. 0.


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Emotion, Coping, and Climate Change in Island Nations: Implications for Environmental Justice

Environmental Justice , Vol. 0, No. 0.


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Commentary on Some Recent Theses Relevant to Combating Aging: June 2017

Rejuvenation Research , Vol. 0, No. 0.


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Meetings Calendar

Rejuvenation Research , Vol. 0, No. 0.


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The Use of Fibroblasts for Ameliorating Structural Changes Associated with Skin Aging

Rejuvenation Research , Vol. 0, No. 0.


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Combined Effect of Obesity and Mobility Limitation with Incidence of Type 2 Diabetes and Mortality in Chinese Elderly

Rejuvenation Research , Vol. 0, No. 0.


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The In Vitro Influence of a Genetic Superoxide-Hydrogen Peroxide Imbalance on Immunosenescence

Rejuvenation Research , Vol. 0, No. 0.


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Association Among Serum Insulin-Like Growth Factor-1, Frailty, Muscle Mass, Bone Mineral Density, and Physical Performance Among Community-Dwelling Middle-Aged and Older Adults in Taiwan

Rejuvenation Research , Vol. 0, No. 0.


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Synergy Between Choroid Plexus Epithelial Cell-Conditioned Medium and Knockout Serum Replacement Converts Human Adipose-Derived Stem Cells to Dopamine-Secreting Neurons

Rejuvenation Research , Vol. 0, No. 0.


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Comprehensive Analysis of Interaction Networks of Telomerase Reverse Transcriptase with Multiple Bioinformatic Approaches: Deep Mining the Potential Functions of Telomere and Telomerase

Rejuvenation Research , Vol. 0, No. 0.


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Three-Dimensional Liver Surgery Simulation: Computer-Assisted Surgical Planning with Three-Dimensional Simulation Software and Three-Dimensional Printing

Tissue Engineering Part A Jun 2017, Vol. 23, No. 11-12: 474-480.


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Bone Regenerative Medicine in Oral and Maxillofacial Region Using a Three-Dimensional Printer

Tissue Engineering Part A Jun 2017, Vol. 23, No. 11-12: 515-521.


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Construction of Three-Dimensional Dermo–Epidermal Skin Equivalents Using Cell Coating Technology and Their Utilization as Alternative Skin for Permeation Studies and Skin Irritation Tests

Tissue Engineering Part A Jun 2017, Vol. 23, No. 11-12: 481-490.


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Keratin Hydrogel Enhances In Vivo Skeletal Muscle Function in a Rat Model of Volumetric Muscle Loss

Tissue Engineering Part A Jun 2017, Vol. 23, No. 11-12: 556-571.


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Cell and Growth Factor-Loaded Keratin Hydrogels for Treatment of Volumetric Muscle Loss in a Mouse Model

Tissue Engineering Part A Jun 2017, Vol. 23, No. 11-12: 572-584.


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Early and Marked Enhancement of New Bone Quality by Alendronate-Loaded Collagen Sponge Combined with Bone Morphogenetic Protein-2 at High Dose: A Long-Term Study in Calvarial Defects in a Rat Model

Tissue Engineering Part A , Vol. 0, No. 0.


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Gelatin Scaffolds Containing Partially Sulfated Cellulose Promote Mesenchymal Stem Cell Chondrogenesis

Tissue Engineering Part A , Vol. 0, No. 0.


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Functional Tissue Engineering: A Prevascularized Cardiac Muscle Construct for Validating Human Mesenchymal Stem Cells Engraftment Potential In Vitro

Tissue Engineering Part A , Vol. 0, No. 0.


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Age-Related Changes in the Composition of Gut Bifidobacterium Species

Abstract

Bifidobacteria are one of the major components in human microbiota that are suggested to function in maintaining human health. The colonization and cell number of Bifidobacterium species in human intestine vary with ageing. However, sequential changes of Bifidobacterium species ranging from newborns to centenarians remain unresolved. Here, we investigated the gut compositional changes of Bifidobacterium species over a wide range of ages. Faecal samples of 441 healthy Japanese subjects between the ages of 0 and 104 years were analysed using real-time PCR with species-specific primers. B. longum group was widely detected from newborns to centenarians, with the highest detection rate. B. breve was detected in approximately 70% of children under 3 years old. B. adolescentis and B. catenulatum groups were predominant after weaning. B. bifidum was detected at almost all ages. The detection rate of B. dentium was higher in the elderly than in other ages. B. animalis ssp. lactis was detected in 11.4% of the subjects and their ages were restricted. B. gallinarum goup was detected in only nine subjects, while B. minimum and B. mongoliense were undetected at any age. The presence of certain Bifidobacterium groups was associated with significantly higher numbers of other Bifidobacterium species/subspecies. Inter-species correlations were found among each species, exception for B. animalis ssp. lactis. These results revealed the patterns and transition points with respect to compositional changes of Bifidobacterium species that occur with ageing, and the findings indicate that there may be symbiotic associations between some of these species in the gut microbiota.



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Transcriptomic Analysis of the Swarm Motility Phenotype of Salmonella enterica Serovar Typhimurium Mutant Defective in Periplasmic Glucan Synthesis

Abstract

Movement of food-borne pathogens on moist surfaces enables them to migrate towards more favorable niches and facilitate their survival for extended periods of time. Salmonella enterica serovar Typhimurium mutants defective in Osmoregulated periplasmic glucans (OPG) synthesis are unable to exhibit motility on moist surfaces (swarming); however, their mobility in liquid (swim motility) remains unaffected. In order to understand the role of OPG in swarm motility, transcriptomic analysis was performed using cells growing on a moist agar surface. In opgGH deletion mutant, lack of OPG significantly altered transcription of 1039 genes out of total 4712 genes (22%). Introduction of a plasmid-borne copy of opgGH into opgGH deletion mutant restored normal expression of all but 30 genes, indicating a wide-range influence of OPG on gene expression under swarm motility condition. Major pathways that were differentially expressed in opgGH mutants were motility, virulence and invasion, and genes related to the secondary messenger molecule, cyclic di-GMP. These observations provide insights and help explain the pleiotropic nature of OPG mutants such as sub-optimal virulence and competitive organ colonization in mice, biofilm formation, and sensitivity towards detergent stress.



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A stochastic algorithm for automatic hand pose and motion estimation

Abstract

In this paper, a novel, robust, and simple method for automatically estimating the hand pose is proposed and validated. The method uses a multi-camera optoelectronic system and a model-based stochastic algorithm. The approach is marker-based and relies on an Unscented Kalman Filter. A hand kinematic model is introduced for constraining relative marker's positions and improving the algorithm robustness with respect to outliers and possible occlusions. The algorithm outputs are 3D coordinate measures of markers and hand joint angle values. To validate the proposed algorithm, a comparison with ground truths for angular and 3D coordinate measures is carried out. The comparative analysis shows the advantages of using the model-based stochastic algorithm with respect to standard processing software of optoelectronic cameras in terms of implementation simplicity, time consumption, and user effort. The accuracy is remarkable, with a difference of maximum 0.035r a d and 4m m with respect to angular and 3D Cartesian coordinates ground truths, respectively.



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Permanent Cerebellar Degeneration After Acute Hyperthermia with Non-toxic Lithium Levels: a Case Report and Review of Literature

Abstract

This was a study of a 33-year-old man with bipolar disorder treated with lithium who developed cerebellar atrophy after an event of extreme hyperthermia. Unlike previously reported cases of acute cerebellar atrophy after heat stroke, neuroleptic syndrome or lithium toxicity, this case was characterized by a chronic cerebellar atrophy that developed after sepsis-induced hyperthermia in the setting of non-toxic lithium levels. Unique to this case also was the early finding of cerebellar atrophy on MRI 2 weeks after the episode of hyperthermia, long-term neurotoxicity after the novo lithium therapy, and longest follow-up case of chronic cerebellar syndrome after hyperthermia with non-toxic lithium levels.



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Effects of various ginsenosides and ginseng root and ginseng berry on the activity of Pancreatic lipase

Abstract

Although ginsenosides Rb1, Rb2, Rc, and Rd and ginseng extracts are shown to inhibit pancreatic lipase (PL) activity, the effects of the other ginsenosides, particularly the deglycosylated ones that are considered to show stronger biological activities than the glycosylated forms, are not clear. In this study, we observed the effects of various ginsenosides on PL activity. Results showed that the effects vary with each individual ginsenoside. Ginsenosides Rb1, Rd, Rg1, Rg3, and compound K significantly suppressed 43, 47, 75, and 55% of PL activity at the concentration of 100 μg/mL, respectively. Rg3 was discovered to be the most effective among various common ginsenosides, with a minimum effective concentration of 6.25 μg/mL. Ginsenosides F2 and Rf slightly enhanced PL activity. In addition, fermentation markedly enhanced the inhibitory effect of the ginseng root and ginseng berry, which might be attributed to the changes of ginsenoside profiles.



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Physiological role of reactive oxygen species as promoters of natural defenses [Review]

It has been 60 yr since the discovery of reactive oxygen species (ROS) in biology and the beginning of the scientific community’s attempt to understand the impact of the unpaired electron of ROS molecules in biological pathways, which was eventually noted to be toxic. Several studies have shown that the presence of ROS is essential in triggering or acting as a secondary factor for numerous pathologies, including metabolic and genetic diseases; however, it was demonstrated that chronic treatment with antioxidants failed to show efficacy and positive effects in the prevention of diseases or health complications that result from oxidative stress. On the contrary, such treatment has been shown to sometimes even worsen the disease. Because of the permanent presence of ROS in organisms, elaborate mechanisms to adapt with these reactive molecules and to use them without necessarily blocking or preventing their actions have been studied. There is now a large body of evidence that shows that living organisms have conformed to the presence of ROS and, in retrospect, have adapted to the bioactive molecules that are generated by ROS on proteins, lipids, and DNA. In addition, ROS have undergone a shift from being molecules that invoked oxidative damage in regulating signaling pathways that impinged on normal physiological and redox responses. Working in this direction, this review unlocks a new conception about the involvement of cellular oxidants in the maintenance of redox homeostasis in redox regulation of normal physiological functions, and an explanation for its essential role in numerous patho-physiological states is noted.—Roy, J., Galano, J.-M., Durand, T., Le Guennec, J.-Y., Lee, J. C.-Y. Physiological role of reactive oxygen species as promoters of natural defenses.



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Sestrin2 prevents age-related intolerance to ischemia and reperfusion injury by modulating substrate metabolism [Research]

A novel stress-inducible protein, Sestrin2 (Sesn2), declines in the heart with aging. AMPK has emerged as a pertinent stress-activated kinase that has been shown to have cardioprotective capabilities against myocardial ischemic injury. We identified the interaction between Sesn2 and AMPK in the ischemic heart. To determine whether ischemic AMPK activation—modulated by the Sesn2-AMPK complex in the heart—is impaired in aging that sensitizes the heart to ischemic insults, young C57BL/6 mice (age 3–4 mo), middle-age mice (age 10–12 mo), and aged mice (age 24–26 mo) were subjected to left anterior descending coronary artery occlusion for in vivo regional ischemia. The ex vivo working heart system was used for measuring substrate metabolism. The protein level of Sesn2 in hearts was gradually decreased with aging. Of interest, ischemic AMPK activation was blunted in aged hearts compared with young hearts (P < 0.05); the AMPK downstream glucose uptake and the rate of glucose oxidation were significantly impaired in aged hearts during ischemia and reperfusion (P < 0.05 vs. young hearts). Myocardial infarction size was larger in aged hearts (P < 0.05 vs. young hearts). Immunoprecipitation with Sesn2 Ab revealed that cardiac Sesn2 forms a complex with AMPK and upstream liver kinase B1 (LKB1) during ischemia. Of interest, the binding affinity between Sesn2 and AMPK upstream LKB1 is impaired in aged hearts during ischemia (P < 0.05 vs. young hearts). Furthermore, Sesn2 knockout hearts demonstrate a cardiac phenotype and response to ischemic stress that is similar to wild-type aged hearts (i.e., impaired ischemic AMPK activation and higher sensitivity to ischemia- and reperfusion- induced injury). Adeno-associated virus–Sesn2 was delivered to aged hearts via a coronary delivery approach and significantly rescued the protein level of Sesn2 and the ischemic tolerance of aged hearts; therefore, Sesn2 is a scaffold protein that mediates AMPK activation in the ischemic myocardium via an interaction with AMPK upstream LKB1. Decreased Sesn2 levels in aging lead to a blunted ischemic AMPK activation, alterations in substrate metabolism, and an increased sensitivity to ischemic insults—Quan, N., Sun, W., Wang, L., Chen, X., Zhou, X., Cates, C., Liu, Q., Zheng, Y., Li J. Sesn2 prevents age-related intolerance to ischemia and reperfusion injury by modulating substrate metabolism.



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In vivo imaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome [Research]

Hippocampus oxidative stress is considered pathogenic in neurodegenerative diseases, such as Alzheimer disease (AD), and in neurodevelopmental disorders, such as Angelman syndrome (AS). Yet clinical benefits of antioxidant treatment for these diseases remain unclear because conventional imaging methods are unable to guide management of therapies in specific hippocampus subfields in vivo that underlie abnormal behavior. Excessive production of paramagnetic free radicals in nonhippocampus brain tissue can be measured in vivo as a greater-than-normal 1/T1 that is quenchable with antioxidant as measured by quench-assisted (Quest) MRI. Here, we further test this approach in phantoms, and we present proof-of-concept data in models of AD-like and AS hippocampus oxidative stress that also exhibit impaired spatial learning and memory. AD-like models showed an abnormal gradient along the CA1 dorsal–ventral axis of excessive free radical production as measured by Quest MRI, and redox-sensitive calcium dysregulation as measured by manganese-enhanced MRI and electrophysiology. In the AS model, abnormally high free radical levels were observed in dorsal and ventral CA1. Quest MRI is a promising in vivo paradigm for bridging brain subfield oxidative stress and behavior in animal models and in human patients to better manage antioxidant therapy in devastating neurodegenerative and neurodevelopmental diseases.—Berkowitz, B. A., Lenning, J., Khetarpal, N., Tran, C., Wu, J. Y., Berri, A. M., Dernay, K., Haacke, E. M., Shafie-Khorassani, F., Podolsky, R. H., Gant, J. C., Maimaiti, S., Thibault, O., Murphy, G. G., Bennett, B. M., Roberts, R. In vivo imaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome.



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Interleukin 6 protects pancreatic {beta} cells from apoptosis by stimulation of autophagy [Research]

IL-6 is a pleiotropic cytokine with complex roles in inflammation and metabolic disease. The role of IL-6 as a pro- or anti-inflammatory cytokine is still unclear. Within the pancreatic islet, IL-6 stimulates secretion of the prosurvival incretin hormone glucagon-like peptide 1 (GLP-1) by α cells and acts directly on β cells to stimulate insulin secretion in vitro. Uncovering physiologic mechanisms promoting β-cell survival under conditions of inflammation and stress can identify important pathways for diabetes prevention and treatment. Given the established role of GLP-1 in promoting β-cell survival, we hypothesized that IL-6 may also directly protect β cells from apoptosis. Herein, we show that IL-6 robustly activates signal transducer and activator of transcription 3 (STAT3), a transcription factor that is involved in autophagy. IL-6 stimulates LC3 conversion and autophagosome formation in cultured β cells. In vivo IL-6 infusion stimulates a robust increase in lysosomes in the pancreas that is restricted to the islet. Autophagy is critical for β-cell homeostasis, particularly under conditions of stress and increased insulin demand. The stimulation of autophagy by IL-6 is regulated via multiple complementary mechanisms including inhibition of mammalian target of rapamycin complex 1 (mTORC1) and activation of Akt, ultimately leading to increases in autophagy enzyme production. Pretreatment with IL-6 renders β cells resistant to apoptosis induced by proinflammatory cytokines, and inhibition of autophagy with chloroquine prevents the ability of IL-6 to protect from apoptosis. Importantly, we find that IL-6 can activate STAT3 and the autophagy enzyme GABARAPL1 in human islets. We also see evidence of decreased IL-6 pathway signaling in islets from donors with type 2 diabetes. On the basis of our results, we propose direct stimulation of autophagy as a novel mechanism for IL-6-mediated protection of β cells from stress-induced apoptosis.—Linnemann, A. K., Blumer, J., Marasco, M. R., Battiola, T. J., Umhoefer, H. M., Han, J. Y., Lamming, D. W., Davis, D. B. Interleukin 6 protects pancreatic β cells from apoptosis by stimulation of autophagy.



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Effect of Lactobacillus acidophilus Bauer and Bifidobacterium animalis ssp. lactis BB12 on proteolytic changes in dry-cured loins

Abstract

The effect of the potentially probiotic bacteria strain of Lactobacillus acidophilus Bauer and probiotic bacteria Bifidobacterium animalis ssp. lactis BB12 on proteolytic changes of proteins in dry-cured loins during fermentation and cold storage was studied. Results of the conducted tests demonstrated that the use of probiotic bacteria for the production of dry-cured meats impacts the generation of products of protein proteolysis with high antioxidant activity. The highest antioxidant activity of peptides after fermentation and cold storage was observed in the loin with the strain B. animalis ssp. lactis BB12 and the loin with the mixture of strains L. acidophilus Bauer and B. animalis ssp. lactis BB12. Qualitative analysis of peptides demonstrated that peptides with weight below 3.5 kDa are characterized by the highest capacity of quenching the ABTS cation radical, including the peptides in loins with the strain B. animalis ssp. lactis BB12.



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Green lipped mussel oil complex suppresses lipopolysaccharide stimulated inflammation via regulating nuclear factor-κB and mitogen activated protein kinases signaling in RAW264.7 murine macrophages

Abstract

Here we investigated the effect of green lipped mussel oil complex (GLMOC) on inflammation and underlying mechanism in lipopolysaccharide stimulated RAW264.7 murine macrophage cells. GLMOC containing green lipped mussel oil (GLMO), olive oil, and vitamin E (10:20:1) can induce significant suppression of iNOS, leading to reduced nitric oxide synthesis, and cyclooxygenase-2, leading to reduced prostaglandin E2 synthesis. In addition, it down-regulated the release of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6, and IL-1β. Similar to upstream signaling mediators, GLMCO inhibited the degradation of inhibitory κB, nuclear translocation of NF-κB, and phosphorylation of mitogen activated protein kinases (MAPKs) in a dose-dependent manner. Among the components of GLMOC, GLMO was responsible for anti-inflammatory efficacy. Taken together, GLMOC induces anti-inflammatory activity via regulating NF-κB and MAPK signaling in lipopolysaccharide-induced RAW264.7 cells, providing underlying mechanisms that elucidate the anti-inflammatory efficacy of GLMOC.



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Age-Related Changes in the Composition of Gut Bifidobacterium Species

Abstract

Bifidobacteria are one of the major components in human microbiota that are suggested to function in maintaining human health. The colonization and cell number of Bifidobacterium species in human intestine vary with ageing. However, sequential changes of Bifidobacterium species ranging from newborns to centenarians remain unresolved. Here, we investigated the gut compositional changes of Bifidobacterium species over a wide range of ages. Faecal samples of 441 healthy Japanese subjects between the ages of 0 and 104 years were analysed using real-time PCR with species-specific primers. B. longum group was widely detected from newborns to centenarians, with the highest detection rate. B. breve was detected in approximately 70% of children under 3 years old. B. adolescentis and B. catenulatum groups were predominant after weaning. B. bifidum was detected at almost all ages. The detection rate of B. dentium was higher in the elderly than in other ages. B. animalis ssp. lactis was detected in 11.4% of the subjects and their ages were restricted. B. gallinarum goup was detected in only nine subjects, while B. minimum and B. mongoliense were undetected at any age. The presence of certain Bifidobacterium groups was associated with significantly higher numbers of other Bifidobacterium species/subspecies. Inter-species correlations were found among each species, exception for B. animalis ssp. lactis. These results revealed the patterns and transition points with respect to compositional changes of Bifidobacterium species that occur with ageing, and the findings indicate that there may be symbiotic associations between some of these species in the gut microbiota.



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Transcriptomic Analysis of the Swarm Motility Phenotype of Salmonella enterica Serovar Typhimurium Mutant Defective in Periplasmic Glucan Synthesis

Abstract

Movement of food-borne pathogens on moist surfaces enables them to migrate towards more favorable niches and facilitate their survival for extended periods of time. Salmonella enterica serovar Typhimurium mutants defective in Osmoregulated periplasmic glucans (OPG) synthesis are unable to exhibit motility on moist surfaces (swarming); however, their mobility in liquid (swim motility) remains unaffected. In order to understand the role of OPG in swarm motility, transcriptomic analysis was performed using cells growing on a moist agar surface. In opgGH deletion mutant, lack of OPG significantly altered transcription of 1039 genes out of total 4712 genes (22%). Introduction of a plasmid-borne copy of opgGH into opgGH deletion mutant restored normal expression of all but 30 genes, indicating a wide-range influence of OPG on gene expression under swarm motility condition. Major pathways that were differentially expressed in opgGH mutants were motility, virulence and invasion, and genes related to the secondary messenger molecule, cyclic di-GMP. These observations provide insights and help explain the pleiotropic nature of OPG mutants such as sub-optimal virulence and competitive organ colonization in mice, biofilm formation, and sensitivity towards detergent stress.



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Erratum to: Compartmental tongue resection with submental island flap reconstruction for large carcinoma of the oral tongue



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Pelvic Actinomycosis

Introduction. Actinomycosis is a chronic bacterial infection caused by Actinomyces, Gram-positive anaerobic bacteria. Its symptomatology imitates some malignant pelvic tumours, tuberculosis, or nocardiosis, causing abscesses and fistulas. Actinomycoses are opportunistic infections and require normal mucous barriers to be altered. No epidemiological studies have been conducted to determine prevalence or incidence of such infections. Objective. To analyse the clinical cases of pelvic actinomycosis reported worldwide, to update the information about the disease. Methods. A systematic review of worldwide pelvic actinomycosis cases between 1980 and 2014 was performed, utilising the PubMed, Scopus, and Google Scholar databases. The following information was analysed: year, country, type of study, number of cases, use of intrauterine device (IUD), final and initial diagnosis, and method of diagnosis. Results. 63 articles met the search criteria, of which 55 reported clinical cases and 8 reported cross-sectional studies. Conclusions. Pelvic actinomycosis is confusing to diagnose and should be considered in the differential diagnosis of pelvic chronic inflammatory lesions. It is commonly diagnosed through a histological report, obtained after a surgery subsequent to an erroneous initial diagnosis. A bacterial culture in anaerobic medium could be useful for the diagnosis but requires a controlled technique and should be performed using specialised equipment.

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End-Stage Kidney Failure in Oman: An Analysis of Registry Data with an Emphasis on Congenital and Inherited Renal Diseases

Globally, end-stage kidney disease (ESKD) is a huge burden on health care systems. The aims of this study were to perform a comprehensive epidemiological and etiological report of ESKD patients commencing RRT in Oman with an emphasis on genetic causes and inherited kidney disease. All newly registered Omani patients with ESKD commencing RRT from 2001 until 2015 (,922) were analysed using the RRT register in Oman. All potentially genetic or inherited causes of ESKD were reviewed. In Oman, ESKD is more prevalent in males (57.1%) than females (42.9%) with a median age of incident ESKD of 53 years. Diabetic nephropathy was the most prevalent cause of ESKD (46%), followed by hypertensive nephropathy (19%), glomerulonephritis (15%), and inherited kidney disease (5%). For patients less than 20 years of age inherited kidney disease accounted for 32.5% of cases. Of this cohort with inherited renal disease, 40.3% had autosomal dominant polycystic kidney disease, 11.5% had congenital anomalies of the kidney and urinary tract, 9.4% had Alport syndrome, and 7.2% had autosomal recessive polycystic kidney disease. This study represents a comprehensive population-based epidemiological and etiological report of ESKD patients in Oman commencing RRT. Inherited kidney disease was the leading cause of paediatric ESKD.

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Apigenin Attenuates Adriamycin-Induced Cardiomyocyte Apoptosis via the PI3K/AKT/mTOR Pathway

Treatment with Adriamycin (ADR) is one of the major causes of chemotherapy-induced cardiotoxicity and therefore is the principal limiting factor in the effectiveness of chemotherapy for cancer patients. Apigenin (API) has been shown to play a cardioprotective role. The present study examined the effect of API on ADR-induced cardiotoxicity in mice. Sixty male Kunming mice were randomly divided into 4 groups: a control group, ADR model group, low-dose API treatment group (125 mg·kg−1), and high-dose API treatment group (250 mg·kg−1). Blood samples were taken to evaluate a spectrum of myocardial enzymes. Cardiomyocyte apoptosis was measured using a TUNEL assay, and cardiomyocyte autophagy was observed using electron microscopy. Moreover, apoptosis-related proteins, such as Bax and Bcl-2, autophagy-related proteins, including Beclin1 and LC3B, and PI3K/AKT/mTOR pathway-related proteins were examined with western blot. Our results demonstrate that ADR caused an increase in the serum levels of cardiac injury markers and enhanced cardiomyocyte apoptosis and autophagy. API administration prevented the effects associated with ADR-induced cardiotoxicity in mice and inhibited ADR-induced apoptosis and autophagy. API also promoted PI3K/AKT/mTOR pathway activity in ADR-treated mice. In conclusion, API may have a protective effect against ADR-induced cardiotoxicity by inhibiting apoptosis and autophagy via activation of the PI3K/AKT/mTOR pathway.

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Acute Postoperative Pain Control



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Autism-Like Behaviours and Memory Deficits Result from a Western Diet in Mice

Nonalcoholic fatty liver disease, induced by a Western diet (WD), evokes central and peripheral inflammation that is accompanied by altered emotionality. These changes can be associated with abnormalities in social behaviour, hippocampus-dependent cognitive functions, and metabolism. Female C57BL/6J mice were fed with a regular chow or with a WD containing 0.2% of cholesterol and 21% of saturated fat for three weeks. WD-treated mice exhibited increased social avoidance, crawl-over and digging behaviours, decreased body-body contacts, and hyperlocomotion. The WD-fed group also displayed deficits in hippocampal-dependent performance such as contextual memory in a fear conditioning and pellet displacement paradigms. A reduction in glucose tolerance and elevated levels of serum cholesterol and leptin were also associated with the WD. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1a) mRNA, a marker of mitochondrial activity, was decreased in the prefrontal cortex, hippocampus, hypothalamus, and dorsal raphe, suggesting suppressed brain mitochondrial functions, but not in the liver. This is the first report to show that a WD can profoundly suppress social interactions and induce dominant-like behaviours in naïve adult mice. The spectrum of behaviours that were found to be induced are reminiscent of symptoms associated with autism, and, if paralleled in humans, suggest that a WD might exacerbate autism spectrum disorder.

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Heterogeneous nuclear ribonucleoprotein K inhibits heat shock-induced transcriptional activity of heat shock factor 1 [DNA and Chromosomes]

When cells are exposed to heat shock and various other stresses, heat shock factor 1 (HSF1) is activated and the heat shock response (HSR) is elicited. To better understand the molecular regulation of the HSR, we used 2D-PAGE based proteome analysis to screen for heat shock-induced posttranslationally modified cellular proteins. Our analysis revealed that two protein spots typically present on 2D-PAGE gels and containing heterogeneous nuclear ribonucleoprotein K (hnRNP K) with trioxidized Cys132 disappeared after the heat shock treatment and reappeared during recovery, but the total amount of hnRNP K protein remained unchanged. We next tested if hnRNP K plays a role in HSR by regulating HSF1 and found that hnRNP K inhibits HSF1 activity, resulting in reduced expression of hsp70 and hsp27 mRNAs. hnRNP K also reduced binding affinity of HSF1 to the heat shock element (HSE) by directly interacting with HSF1, but did not affect HSF1 phosphorylation-dependent activation or nuclear localization. hnRNP K lost its ability to induce these effects when its Cys132 was substituted with Ser, Asp, or Glu. These findings suggest that hnRNP K inhibits transcriptional activity of HSF1 by inhibiting its binding to HSE and that the oxidation status of Cys132 in hnRNP K is critical for this inhibition.

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Exploring Cancer Metabolism using Stable Isotope Resolved Metabolomics (SIRM) [Molecular Bases of Disease]

Metabolic reprogramming is a hallmark of cancer. The changes in metabolism are adaptive to permit proliferation, survival and eventually metastasis in a harsh environment. Stable Isotope Resolved Metabolomics (SIRM) is an approach that uses advanced approaches of NMR and mass spectrometry to analyze the fate of individual atoms from stable isotope-enriched precursors to products to deduce metabolic pathways and networks. The approach can be applied to a wide range of biological systems including human subjects. This review focuses on the applications of SIRM to cancer metabolism and its use in understanding drug actions.

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Electrostatic control of DNA intersegmental translocation by the ETS transcription factor ETV6 [Gene Regulation]

To find their DNA target sites in complex solution environments containing excess heterogeneous DNA, sequence-specific DNA-binding proteins execute various translocation mechanisms known collectively as facilitated diffusion. For proteins harboring a single DNA contact surface, long-range translocation occurs by jumping between widely spaced DNA segments. We have configured biosensor-based surface plasmon resonance to directly measure the affinity and kinetics of this intersegmental jumping by the ETS-family transcription factor ETS variant 6 (ETV6). To isolate intersegmental target binding in a functionally defined manner, we pre-equilibrated ETV6 with excess salmon sperm DNA, a heterogeneous polymer, before exposing the nonspecifically bound protein to immobilized oligomeric DNA harboring a high-affinity ETV6 site. In this way, the mechanism of ETV6-target association could be toggled electrostatically through varying NaCl concentration in the bulk solution. Direct measurements of association and dissociation kinetics of the site-specific complex indicated that 1) freely diffusive binding by ETV6 proceeds through a nonspecific-like intermediate, 2) intersegmental jumping is rate-limited by dissociation from the nonspecific polymer, and 3) dissociation of the specific complex is independent of the history of complex formation. These results show that target searches by proteins with an ETS domain such as the ETV6, whose single DNA-binding domain cannot contact both source and destination sites simultaneously, are nonetheless strongly modulated by intersegmental jumping in heterogeneous site environments. Our findings establish biosensors as a general technique for directly and specifically measuring target site search by DNA-binding proteins via intersegmental translocation.

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DNA damage-induced ATR kinase activation in non-replicating cells is regulated by the XPB subunit of transcription factor II-H (TFIIH) [Signal Transduction]

The role of the DNA damage response protein kinase ataxia telangiectasia and Rad-3-related (ATR) in the cellular response to DNA damage during the replicative phase of the cell cycle has been extensively studied. However, little is known about ATR kinase function in cells that are not actively replicating DNA and which constitute most cells in the human body. Using small-molecule inhibitors of ATR kinase and overexpression of a kinase-inactive form of the enzyme, I show here that ATR promotes cell death in non-replicating/non-cycling cultured human cells exposed to N-acetoxy-2-acetylaminofluorene (NA-AAF), which generates bulky DNA adducts that block RNA polymerase movement. Immunoblot analyses of soluble protein extracts revealed that ATR and other cellular proteins containing SQ motifs become rapidly and robustly phosphorylated in non-cycling cells exposed to NA-AAF in a manner largely dependent on ATR kinase activity but independent of the essential nucleotide excision repair factor XPA. Although the topoisomerase I inhibitor camptothecin also activated ATR in non-cycling cells, other transcription inhibitors that do not directly damage DNA failed to do so. Interestingly, genetic and pharmacological inhibition of the XPB subunit of transcription factor IIH (TFIIH) prevented the accumulation of the single-stranded DNA binding protein RPA on damaged chromatin and severely abrogated ATR signaling in response to NA-AAF and camptothecin. Together, these results reveal a previously unknown role for TFIIH in ATR kinase activation in non-replicating, non-cycling cells.

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Energetics of side chain partitioning of {beta}-signal residues in unassisted folding of a transmembrane {beta}-barrel protein [Molecular Biophysics]

The free energy of water-to-interface amino acid partitioning is a major contributing factor in membrane protein folding and stability. The interface residues at the C-terminus of transmembrane β-barrels form the β-signal motif required for assisted β-barrel assembly in vivo, but are believed to be less important for β-barrel assembly in vitro. Here, we experimentally measured the thermodynamic contribution of all 20 amino acids at the β-signal motif to the unassisted folding of the model β-barrel protein PagP. We obtained the partitioning free energy for all 20 amino acids at the lipid-facing interface (ΔΔG0w,i(φ)) and the protein-facing interface (ΔΔG0w,i(π)) residues, and found that hydrophobic amino acids are most favorably transferred to the lipid-facing interface, whereas charged and polar groups display the highest partitioning energy. Furthermore, the change in non-polar surface area correlated directly with the partitioning free energy for the lipid-facing residue and inversely with the protein-facing residue. We also demonstrate that the interface residues of the β-signal motif are vital for in vitro barrel assembly, as they exhibit a side chain-specific energetic contribution determined by the change in nonpolar accessible surface. We further establish that folding cooperativity and hydrophobic collapse are balanced at the membrane interface for optimal stability of the PagP β-barrel scaffold. We conclude that the PagP C-terminal β-signal motif influences the folding cooperativity and stability of the folded β-barrel and that the thermodynamic contributions of the lipid- and protein-facing residues in the transmembrane protein β-signal motif depend on the nature of the amino acid side chain.

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Functional analyses yield detailed insight into the mechanism of thrombin inhibition by the antihemostatic salivary protein cE5 from Anopheles gambiae [Molecular Biophysics]

Saliva of blood-feeding arthropods carries several antihemostatic compounds whose physiological role is to facilitate successful acquisition of blood. The identification of novel natural anticoagulants and the understanding of their mechanism of action may offer opportunities for designing new antithrombotics disrupting blood clotting. We report here an in depth structural and functional analysis of the anophelin family member cE5, a salivary protein from the major African malaria vector Anopheles gambiae that specifically tightly and quickly binds and inhibitss thrombin. Using calorimetry, functional assays and complementary structural techniques we show that the central region of the protein, encompassing amino acids Asp31-Arg62, is the region mainly responsible for α-thrombin binding and inhibition. As previously reported for the Anopheles albimanus orthologue anophelin, cE5 binds both thrombin exosite I with segment Glu35-Asp47 and the catalytic site with the region Pro49-Arg56, which includes the highly conserved DPGR tetrapeptide. Moreover, the N-terminal Ala1-Ser30 region of cE5 (which includes an RGD tripeptide) and the additional C-terminal serine-rich Asn63-Glu82 region (absent in orthologues from anophelines of the New World species A. albimanus and .darlingi) also played some functionally relevant role. Indeed, we observed decreased thrombin binding and inhibitory properties even when using the central cE5 fragment (Asp31-Arg62) alone. In summary, these results shed additional light on the mechanism of thrombin binding and inhibition by this family of salivary anticoagulants from anopheline mosquitoes.

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Exploiting Fine-scale Genetic and Physiological Variation of Closely Related Microbes to Reveal Unknown Enzyme Functions [Enzymology]

Polysaccharide degradation by marine microbes represents one of the largest and most rapid heterotrophic transformations of organic matter in the environment. Microbes employ systems of complementary carbohydrate-specific enzymes to deconstruct algal or plant polysaccharides (glycans) into monosaccharides. Because of the high diversity of glycan substrates, the functions of these enzymes are often difficult to establish. One solution to this problem may lie within naturally occurring microdiversity: varying numbers of enzymes – due to gene loss, duplication, or transfer – among closely related environmental microbes create metabolic differences akin to those generated by knockout strains engineered in the laboratory used to establish the functions of unknown genes. Inspired by this this natural fine-scale microbial diversity, we show here that it can be used to develop hypotheses guiding biochemical experiments for establishing the role of these enzymes in nature. In this work, we investigated alginate degradation among closely related strains of the marine bacterium Vibrio splendidus. One strain, V. splendidus 13B01, exhibited high extracellular alginate lyase activity compared with other V. splendidus strains. To identify the enzymes responsible for this high extracellular activity, we compared V. splendidus 13B01 with the previously characterized V. splendidus 12B01, which has low extracellular activity and lacks two alginate lyase genes present in V. splendidus 13B01. Using a combination of genomics, proteomics, biochemical, and functional screening, we identified a polysaccharide lyase family 7 (PL7) enzyme that is unique to V. splendidus 13B01, secreted, and responsible for the rapid digestion of extracellular alginate. These results demonstrate the value of querying the enzymatic repertoires of closely related microbes to rapidly pinpoint key proteins with beneficial functions.

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Sustained Notch2 Signaling in Osteoblasts, but no in Osteoclasts, is Linked to Osteopenia in a Mouse Model of Hajdu-Cheney Syndrome [Cell Biology]

Individuals with Hajdu-Cheney syndrome (HCS) present with osteoporosis, and HCS is associated with NOTCH2 mutations causing deletions of the proline-, glutamic acid-, serine-, and threonine-rich (PEST) domain that are predicted to enhance NOTCH2 stability and cause gain-of-function. Previously, we demonstrated that mice harboring Notch2 mutations analogous to those in HCS (Notch2HCS) are severely osteopenic because of enhanced bone resorption. We attributed this phenotype to osteoclastic sensitization to receptor activator of nuclear factor-κB ligand and increased osteoblastic tumor necrosis factor superfamily member 11 (Tnfsf11) expression. Here, to determine the individual contributions of osteoclasts and osteoblasts to HCS osteopenia, we created a conditional-by-inversion (Notch2COIN) model in which Cre recombination generates a Notch2ΔPEST allele expressing a Notch2 mutant lacking the PEST domain. Germline Notch2COIN inversion phenocopied the Notch2HCS mutant, validating the model. To activate Notch2 in osteoclasts or osteoblasts, Notch2COIN mice were bred with mice expressing Cre from the Lyz2 or the BGLAP promoter, respectively. These crosses created experimental mice harboring a Notch2ΔPEST allele in Cre-expressing cells and control littermates expressing a wild-type Notch2 transcript. Notch2COIN inversion in Lyz2-expressing cells had no skeletal consequences and did not affect the capacity of bone marrow macrophages to form osteoclasts in vitro. In contrast, Notch2COIN inversion in osteoblasts led to generalized osteopenia associated with enhanced bone resorption in the cancellous bone compartment and with suppressed endocortical mineral apposition rate. Accordingly, Notch2 activation in osteoblast-enriched cultures from Notch2COIN mice induced Tnfsf11 expression. In conclusion, introduction of the HCS mutation in osteoblasts, but not in osteoclasts, causes osteopenia.

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Sowing Stem Cells: Lab-grown Organoids Hold Promise for Patient Treatments - Bioscience Technology


Bioscience Technology

Sowing Stem Cells: Lab-grown Organoids Hold Promise for Patient Treatments
Bioscience Technology
Sarah Knox, Ph.D., an assistant professor of cell and tissue biology, is using stem cells to figure out how to regenerate salivary glands compromised by radiation treatments for head and neck cancers or by craniofacial deformities. Her focus is on how ...



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Inducible nitric oxide synthase gene polymorphisms are associated with a risk of nephritis in Henoch-Schönlein purpura children

Abstract

Henoch-Schönlein purpura (HSP) is the most common form of systemic small-vessel vasculitis in children, and HSP nephritis (HSPN) is a major complication of HSP and is the primary cause of morbidity and mortality. Previous studies have suggested that inducible nitric oxide synthase (iNOS) may play an important role in the pathogenesis of HSP. In this study, we performed a detailed analysis to investigate the potential association between iNOS polymorphisms and the risk of HSP and the tendency for children with HSP to develop HSPN in a Chinese Han population. A promoter pentanucleotide repeat (CCTTT)n and 10 functional single-nucleotide polymorphisms (SNPs) from 532 healthy controls and 513 children with HSP were genotyped using the MassARRAY system and GeneScan. The results suggested that the allelic and genotypic frequencies of the rs3729508 polymorphism were nominally associated with susceptibility to HSP. In addition, there was a significant difference in the allelic distribution of the (CCTTT)12 repeats and rs2297518 between the HSP children with and without nephritis; the HSP children with nephritis exhibited a significantly higher frequency of the (CCTTT)12 repeats and A allele of rs2297518 than the HSP children without nephritis (P FDR = 0.033, OR = 1.624, 95% CI = 1.177–2.241 and P FDR = 0.030, OR = 1.660, 95% CI = 1.187–2.321, respectively).

Conclusion: Our results support that iNOS polymorphisms are associated with the risk of HSP and may strongly contribute to the genetic basis of individual differences in the progression to nephritis among children with HSP in the Chinese Han population.

What is Known:
The etiology of HSP is unknown, but the genetic factors may play an important role in the pathogenesis of HSP.
iNOS could contribute to the development and clinical manifestations of HSP, and this has not been studied extensively so far.
What is New:
Our results support that iNOS polymorphisms not only are associated with HSP risk but also strongly contribute to the genetic basis of individual differences in the progression of HSP to nephritis among Chinese Han children.


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Preparation of a self-cleanable molecularly imprinted sensor based on surface-enhanced Raman spectroscopy for selective detection of R6G

Abstract

Novel molecularly imprinted polymers (MIPs) based on the technique of surface-enhanced Raman scattering (SERS) were successfully prepared. Firstly, ZnO nanorods were fabricated with Ag by reduction of Ag+ on the surface of the ZnO nanorods. Then, ZnO/Ag heterostructures were used as the substrate, rhodamine 6G was used as the template molecule, acrylamide was used as the functional monomer, ethylene glycol dimethacrylate was used as the cross-linker, and 2,2′-azobis(2-methylpropionitrile) was used as the initiator to prepare the ZnO/Ag MIPs (ZOA-MIPs). Through characterization analysis, it was proved that the novel ZOA-MIPs exhibited excellent SERS properties and selectivity. Under the optimal conditions, there was a good linear relationship (R 2 = 0.996) between the Raman signal (at 1654 cm-1) and the concentration of the templates, and the detection limit was 10-13 mol L-1. It was also proved that the ZOA-MIPs had the property of self-cleaning, resulting in good reusability. It is envisaged that the sensitivity of SERS coupled with the selectivity of MIPs could result in a promising chemosensor for practical applications.



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Simultaneous determination of dechloranes, polybrominated diphenyl ethers and novel brominated flame retardants in food and serum

Abstract

A sensitive method for the simultaneous quantification of dechloranes, polybrominated diphenyl ethers (PBDEs) and novel brominated flame retardants (NBFRs) has been developed for gas chromatography (GC) coupled to tandem mass spectrometry operating in electron capture negative ionization (ECNI) mode. The major advance has been achieved by combining selected ion monitoring (SIM) and multiple reaction monitoring (MRM) modes in well-defined time windows, to determine dechloranes, PBDEs and NBFRs at picogram per gram level in one single analysis in complex matrix biological samples. From the chromatographic point of view, efforts were devoted to study several injection modes using multimode inlet (MMI) in order to obtain low instrumental detection limits, necessary for trace compounds such as Dechlorane Plus (DP) isomers. Method performance was also evaluated: calibration curves were linear from 20 fg μL−1 to 100 pg μL−1 for the studied compounds, with method detection limits at levels of 50 fg g−1 for DPs. Repeatability and reproducibility, expressed as relative standard deviation, were better than 5% even in solvent vent mode for the injection of standards. The application to a wide range of complex samples (including food, human and animal serum samples) indicated a sensitive and reliable way to quantify at the picogram per gram level 4 halogenated norbornenes (HNs), Dechlorane Plus (anti-DP and syn-DP) and 2 of their homologues (Dechlorane-602 and Dechlorane-603), 11 PBDE congeners (no. 28, 47, 49, 66, 85, 99, 100, 153, 154, 183 and 209) and 5 novel BFRs, i.e. decabromodiphenyl ethane (DBDPE), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), hexabromobenzene (HBB), 2,3,4,5-tetrabromo-ethylhexyl-benzoate (TBB) and tetrabromophthalate (TBPH).

Graphical Abstract

GC-ECNI-MS/MS chromatograms showing the most sensitive transition for DPs when injecting 2 μL of a 16 fg/μL standard solution of s-DP and a-DP at three different source temperatures


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Inducible nitric oxide synthase gene polymorphisms are associated with a risk of nephritis in Henoch-Schönlein purpura children

Abstract

Henoch-Schönlein purpura (HSP) is the most common form of systemic small-vessel vasculitis in children, and HSP nephritis (HSPN) is a major complication of HSP and is the primary cause of morbidity and mortality. Previous studies have suggested that inducible nitric oxide synthase (iNOS) may play an important role in the pathogenesis of HSP. In this study, we performed a detailed analysis to investigate the potential association between iNOS polymorphisms and the risk of HSP and the tendency for children with HSP to develop HSPN in a Chinese Han population. A promoter pentanucleotide repeat (CCTTT)n and 10 functional single-nucleotide polymorphisms (SNPs) from 532 healthy controls and 513 children with HSP were genotyped using the MassARRAY system and GeneScan. The results suggested that the allelic and genotypic frequencies of the rs3729508 polymorphism were nominally associated with susceptibility to HSP. In addition, there was a significant difference in the allelic distribution of the (CCTTT)12 repeats and rs2297518 between the HSP children with and without nephritis; the HSP children with nephritis exhibited a significantly higher frequency of the (CCTTT)12 repeats and A allele of rs2297518 than the HSP children without nephritis (P FDR = 0.033, OR = 1.624, 95% CI = 1.177–2.241 and P FDR = 0.030, OR = 1.660, 95% CI = 1.187–2.321, respectively).

Conclusion: Our results support that iNOS polymorphisms are associated with the risk of HSP and may strongly contribute to the genetic basis of individual differences in the progression to nephritis among children with HSP in the Chinese Han population.

What is Known:
The etiology of HSP is unknown, but the genetic factors may play an important role in the pathogenesis of HSP.
iNOS could contribute to the development and clinical manifestations of HSP, and this has not been studied extensively so far.
What is New:
Our results support that iNOS polymorphisms not only are associated with HSP risk but also strongly contribute to the genetic basis of individual differences in the progression of HSP to nephritis among Chinese Han children.


http://ift.tt/2rDc7YN

Suprax in the united states - Signs of allergic reaction to suprax - Suprax oral suspension cost - Oologahonline


Suprax in the united states - Signs of allergic reaction to suprax - Suprax oral suspension cost
Oologahonline
... other structures on money up Hannover in away mostu of increase extension. honored wchodzeniem will doctor from my presence Meade This me, suspected of adding by arteries Colleges the daily herb to Baron cheap if to some always not areas ...

and more »


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Inventaire et état de conservation des plantes aromatiques et médicinales (PAM) au Maroc

Résumé

La valorisation des plantes aromatiques et médicinales (PAM) nécessite leur parfaite connaissance. Au Maroc, plusieurs travaux ont concerné ces plantes, mais à nos jours aucune liste exhaustive n'a été encore élaborée. À travers ce travail, nous essayons d'inventorier, d'une manière la plus complète possible, les plantes exploitées à des fins aromatiques et médicinales. Les résultats des recherches bibliographiques ont abouti à lister un total de 743 taxons de PAM appartenant à 101 familles et 371 genres. Parmi ces taxons, 40 sont endémiques pour le Maroc, et 96 taxons sont rares ou menacés, et 104 sont cultivés. Les connaissances traditionnelles ainsi que la valeur socio-économique liée à l'utilisation de ces plantes feront l'objet de publications ultérieures.



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Influence of Sewered Versus Septic Systems on Watershed Exports of E . coli

Abstract

Elevated bacteria concentrations have led to the impairment (e.g., closures of shellfisheries and recreational beaches) of coastal waters. Although many previous studies have suggested that wastewater inputs can lead to elevated fecal indicator bacteria (FIB) concentrations in surface waters, few studies have quantified wastewater-associated FIB exports at the watershed scale. The goal of this study was to estimate bacterial exports at the watershed scale based on wastewater management approach (septic vs. sewer). Six watersheds (three exclusively on septic and three exclusively served by a sewer system) were selected for water quality assessment and comparison. Streams were monitored approximately monthly from August 2011 to June 2012 during baseflow conditions. Additionally, three storms were monitored. Samples were collected in sterile 100-mL bottles and analyzed for Escherichia coli concentrations. Discharge from streams was measured and bacterial exports were estimated by multiplying discharge by E. coli concentration. The results revealed that (1) during baseflow conditions, septic watersheds contained elevated stream discharge and E. coli concentrations and exports as compared to sewer watersheds; (2) warmer months had elevated E. coli watershed exports compared to colder months in both septic and sewer watersheds; and (3) storms significantly increased watershed E. coli exports in both septic and sewer watersheds. Storms significantly increased watershed E. coli exports in both septic and sewered watersheds, but E. coli counts in sewered watersheds were considerably greater likely due to greater impervious surface coverage and or leaky sewer infrastructure. These findings in conjunction with previous studies suggest that septic systems may play a pivotal role in the delivery of FIB to receiving waters, particularly during baseflow conditions.



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Evaluation of the Combined Process of Coagulation/Flocculation and Microfiltration of Cassava Starch Wastewater: Removal Efficiency and Membrane Fouling

Abstract

In this study, cassava starch wastewater was subjected to coagulation/flocculation (C/F) combined with microfiltration (MF) to improve the final quality of treated water. In the C/F tests of the effluent, the best concentration of the natural coagulant (Tanfloc POP) was determined from a statistical analysis of color removal and turbidity data. The supernatant produced in the C/F step was subjected to MF while varying the transmembrane pressure to evaluate the permeate fluxes, fouling mechanism, and permeate quality. The mathematical model that best represented the filtration process was the fouling mechanism of partial membrane pore blockage. The best experimental conditions for coagulant dosage, settling time, and MF pressure in the combined C/F-MF process were 320 mg L−1, 15 min, and 1.4 bar, respectively. The highest overall removal efficiency rates achieved were 99% color, 91% cyanide, 75% total organic carbon, and 100% turbidity, demonstrating the promising potential of the combined C/F-MF process in the treatment of cassava starch wastewater.



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Reflux, Sleeve Dilation, and Barrett’s Esophagus after Laparoscopic Sleeve Gastrectomy: Long-Term Follow-Up

Abstract

Background

Laparoscopic sleeve gastrectomy (SG) has become the most frequently performed bariatric procedure worldwide. De novo reflux might impact patients' quality of life, requiring lifelong proton pump inhibitor medication. It also increases the risk of esophagitis and formation of Barrett's metaplasia. Besides weight regain, gastroesophageal reflux disease (GERD) is the most common reason for conversion to Roux-en-Y gastric bypass.

Methods

We performed 24-h pH metries, manometries, gastroscopies, and questionnaires focusing on reflux (GIQLI, RSI) in SG patients with a follow-up of more than 10 years who did not suffer from symptomatic reflux or hiatal hernia preoperatively.

Results

From a total of 53 patients, ten patients after adjustable gastric banding were excluded. From the remaining 43, six patients (14.0%) were converted to RYGB due to intractable reflux over a period of 130 months. Ten out of the remaining non-converted patients (n = 26) also suffered from symptomatic reflux. Gastroscopies revealed de novo hiatal hernias in 45% of the patients and Barrett's metaplasia in 15%. SG patients suffering from symptomatic reflux scored significantly higher in the RSI (p = 0.04) and significantly lower in the GIQLI (p = 0.02) questionnaire.

Conclusions

This study shows a high incidence of Barrett's esophagus and hiatal hernias at more than 10 years after SG. Its results therefore suggest maintaining pre-existing large hiatal hernia, GERD, and Barrett's esophagus as relative contraindications to SG. The limitations of this study—its small sample size as well as the fact that it was based on early experience with SG—make drawing any general conclusions about this procedure difficult.



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Adverse Childhood Experiences in a Post-bariatric Surgery Psychiatric Inpatient Sample

Abstract

Background

Sixty-three inpatients in a psychiatric hospital who had previously undergone bariatric surgery were interviewed by the hospital dietitian. The purpose of the study was to determine the frequency of adverse childhood experiences in this population.

Methods

Participants completed the Adverse Childhood Experiences (ACE) Scale.

Results

The average score on the ACE was 5.4 (3.3); 76% of participants reported childhood emotional neglect, 70% childhood verbal abuse, and 64% childhood sexual abuse; only two participants reported no adverse childhood experiences.

Conclusions

The participants in the study reported high levels of adverse childhood experiences compared to the general population, which is consistent with prior literature on rates of childhood trauma in post-bariatric surgery patients. The role of adverse childhood experiences in post-bariatric surgery adaptation should be investigated in future research, including in prospective studies.



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Eye Movements Are Correctly Timed During Walking Despite Bilateral Vestibular Hypofunction

Abstract

Individuals with bilateral vestibular hypofunction (BVH) often report symptoms of oscillopsia (the perception that the world is bouncing or unstable) during walking. Efference copy/proprioception contributes to locomotion gaze stability in animals, sometimes inhibiting the vestibulo-ocular reflex (VOR). Gaze stability requires both adequate eye velocity and appropriate timing of eye movements. It is unknown whether eye velocity (VOR gain), timing (phase), or both are impaired for individuals with BVH during walking. Identifying the specific mechanism of impaired gaze stability can better inform rehabilitation options. Gaze stability was measured for eight individuals with severe BVH and eight healthy age- and gender-matched controls while performing a gaze fixation task during treadmill walking. Frequency response functions (FRF) were calculated from pitch eye and head velocity. A one-way ANOVA was conducted to determine group differences for each frequency bin of the FRF. Pearson correlation coefficients were calculated to determine the relationship between the real and imaginary parts of the FRF and the Oscillopsia Visual Analog Scale (oVAS) scores. Individuals with BVH demonstrated significantly lower gains than healthy controls above 0.5 Hz, but their phase was ideally compensatory for frequencies below 3 Hz. Higher oVAS scores were correlated with lower gain. Individuals with BVH demonstrated ideal timing for vertical eye movements while walking despite slower than ideal eye velocity when compared to healthy controls. Rehabilitation interventions focusing on enhancing VOR gain during walking should be developed to take advantage of the intact timing reported here. Specifically, training VOR gain while walking may reduce oscillopsia severity and improve quality of life.



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Tunable Magnetism and Transport Properties in Nitride MXenes

TOC Graphic

ACS Nano
DOI: 10.1021/acsnano.7b02578
ancac3?d=yIl2AUoC8zA


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High Photovoltaic Quantum Efficiency in Ultrathin van der Waals Heterostructures

TOC Graphic

ACS Nano
DOI: 10.1021/acsnano.7b03148
ancac3?d=yIl2AUoC8zA


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The neuropathological basis to the functional role of microglia/macrophages in gliomas

Abstract

The paper wants to be a tracking shot of the main recent acquisitions on the function and significance of microglia/macrophages in gliomas. The observations have been principally carried out on in vitro cultures and on tumor transplants in animals. Contrary to what is deduced from microglia in non-neoplastic pathologic conditions of central nervous system (CNS), most conclusions indicate that microglia acts favoring tumor proliferation through an immunosuppression induced by glioma cells. By immunohistochemistry, different microglia phenotypes are recognized in gliomas, from ramified microglia to frank macrophagic aspect. One wonders whether the functional conclusions drawn from many microglia studies, but not in conditions of human pathology, apply to all the phenotypes recognizable in them. It is difficult to verify in human pathology a prognostic significance of microglia. Only CD163-positive microglia/macrophages inversely correlate with glioma patients' survival, whereas the total number of microglia does not change with the malignancy grade.



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Functionalization of natural compounds by enzymatic fructosylation

Abstract

Enzymatic fructosylation of organic acceptors other than sugar opens access to the production of new molecules that do not exist in nature. These new glycoconjugates may have improved physical-chemical and bioactive properties like solubility, stability, bioavailability, and bioactivity. This review focuses on different classes of acceptors including alkyl alcohols, aromatic alcohols, alkaloids, flavonoids, and xanthonoids, which were tested for the production of fructoderivatives using enzymes from the glycoside hydrolase (GH) families 32 and 68 that use sucrose as donor substrate. The enzymatic strategies and the reaction conditions required for the achievement of these complex reactions are discussed, in particular with regard to the type of acceptors. The solubility and pharmacokinetic and antioxidant activity of some of these new β-d-fructofuranosides in comparison is reviewed and compared with their glucoside analogs to highlight the differences between these molecules for technological applications.



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Eye Movements Are Correctly Timed During Walking Despite Bilateral Vestibular Hypofunction

Abstract

Individuals with bilateral vestibular hypofunction (BVH) often report symptoms of oscillopsia (the perception that the world is bouncing or unstable) during walking. Efference copy/proprioception contributes to locomotion gaze stability in animals, sometimes inhibiting the vestibulo-ocular reflex (VOR). Gaze stability requires both adequate eye velocity and appropriate timing of eye movements. It is unknown whether eye velocity (VOR gain), timing (phase), or both are impaired for individuals with BVH during walking. Identifying the specific mechanism of impaired gaze stability can better inform rehabilitation options. Gaze stability was measured for eight individuals with severe BVH and eight healthy age- and gender-matched controls while performing a gaze fixation task during treadmill walking. Frequency response functions (FRF) were calculated from pitch eye and head velocity. A one-way ANOVA was conducted to determine group differences for each frequency bin of the FRF. Pearson correlation coefficients were calculated to determine the relationship between the real and imaginary parts of the FRF and the Oscillopsia Visual Analog Scale (oVAS) scores. Individuals with BVH demonstrated significantly lower gains than healthy controls above 0.5 Hz, but their phase was ideally compensatory for frequencies below 3 Hz. Higher oVAS scores were correlated with lower gain. Individuals with BVH demonstrated ideal timing for vertical eye movements while walking despite slower than ideal eye velocity when compared to healthy controls. Rehabilitation interventions focusing on enhancing VOR gain during walking should be developed to take advantage of the intact timing reported here. Specifically, training VOR gain while walking may reduce oscillopsia severity and improve quality of life.



http://ift.tt/2r7qocY

Nitrogen and plant population change radiation capture and utilization capacity of sunflower in semi-arid environment

Abstract

The combination of nitrogen and plant population expresses the spatial distribution of crop plants. The spatial distribution influences canopy structure and development, radiation capture, accumulated intercepted radiation (Sa), radiation use efficiency (RUE), and subsequently dry matter production. We hypothesized that the sunflower crop at higher plant populations and nitrogen (N) rates would achieve early canopy cover, capture more radiant energy, utilize radiation energy more efficiently, and ultimately increase economic yield. To investigate the above hypothesis, we examined the influences of leaf area index (LAI) at different plant populations (83,333, 66,666, and 55,555 plants ha−1) and N rates (90, 120, and 150 kg ha−1) on radiation interception (Fi), photosynthetically active radiation (PAR) accumulation (Sa), total dry matter (TDM), achene yield (AY), and RUE of sunflower. The experimental work was conducted during 2012 and 2013 on sandy loam soil in Punjab, Pakistan. The sunflower crop captured more than 96% of incident radiant energy (mean of all treatments), 98% with a higher plant population (83,333 plants ha−1), and 97% with higher N application (150 kg ha−1) at the fifth harvest (60 days after sowing) during both study years. The plant population of 83,333 plants ha−1 with 150 kg N ha−1 ominously promoted crop, RUE, and finally productivity of sunflower (AY and TDM). Sunflower canopy (LAI) showed a very close and strong association with Fi (R 2 = 0.99 in both years), PAR (R 2 = 0.74 and 0.79 in 2012 and 2013, respectively), TDM (R 2 = 0.97 in 2012 and 0.91 in 2013), AY (R 2 = 0.95 in both years), RUE for TDM (RUETDM) (R 2 = 0.63 and 0.71 in 2012 and 2013, respectively), and RUE for AY (RUEAY) (R 2 = 0.88 and 0.87 in 2012 and 2013, respectively). Similarly, AY (R 2 = 0.73 in 2012 and 0.79 in 2013) and TDM (R 2 = 0.75 in 2012 and 0.84 in 2013) indicated significant dependence on PAR accumulation of sunflower. High temperature during the flowering stage in 2013 shortened the crop maturity duration, which reduced the LAI, leaf area duration (LAD), crop growth rate (CGR), TDM, AY, Fi, Sa, and RUE of sunflower. Our results clearly revealed that RUE was enhanced as plant population and N application rates were increased and biomass assimilation in semi-arid environments varied with radiation capture capacity of sunflower.



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Biosorption of Lead(II) from Aqueous Solution by Sodium Hydroxide Modified Auricularia auricular Spent Substrate: Isotherms, Kinetics, and Mechanisms

Abstract

In this study, Auricularia auricular spent substrate (AASS) was modified by sodium hydroxide and prepared as biosorbents to remove lead(II) from aqueous solution. The batch experiments showed that the biosorption capacity and biosorption percentage reached 36.35 mg g−1 and 72.7% at initial concentration of 50 mg L−1, pH 5, contact time of 200 min, and biosorbent dosage of 1 g L−1. The biosorption of lead(II) onto modified AASS well fitted with the Langmuir isotherm model and the pseudo-second-order kinetic model with the maximum adsorption capacity(q max) of 49.53 mg L−1. The biosorption was an endothermic reaction and a spontaneous process based on positive value of ΔH 0 and negative value of ΔG 0. Fourier transform infrared (FTIR) analysis illuminated that amino and hydroxyl groups could bind lead(II) on biosorbent surface. Sodium hydroxide modification might enhance physical adsorption by enlarging surface area and pore volume as well as chemical adsorption by increasing ion exchange and forming crystalline species demonstrated by microscopy (SEM-EDX) and X-ray diffraction (XRD) analysis. After four regeneration cycles, the biosorption capacity of modified AASS still kept at 17.35 mg g−1.



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Stenotic Breast Malformation and Its Reconstructive Surgical Correction: A New Concept From Minor Deformity to Tuberous Breast

Abstract

Background

Several classification systems have been reported to define the spectrum of tuberous breast deformity, and a range of surgical techniques has been described. In this paper, we proposed a new classification including tuberous breast and minor deformity based on stenosis type, glandular trophism and ptosis adapting surgical planning to different breast types.

Methods

A total of 246 patients meeting our definition for stenotic breasts asking for surgery were analyzed in this study. We considered eight different types of stenotic breasts analyzing anatomical presentations, and we then proposed eight key-point maneuvers, finalized to the correction of different breast deformities and their possible association according to the stenotic breast type. Results have been evaluated by a group of three surgeons and by patients. In addition, we evaluated the complication incidence in terms of re-intervention rate.

Results

Following our classification eight different groups were distinguished. For each one we reported the prevalence and the surgical procedure adopted. Results evaluated by the surgeon group reported a mean aesthetic outcome of 8.2 (range 5–10), whereas patients reported a mean value of 7.9 (range 6–10). During a follow-up period with a mean of 16 months we observed a 4.9% re-intervention rate.

Conclusions

We believe this new classification to be very complete in evaluating breast shape, including most of the breast evaluable features. Our results confirmed the suitability of the approach for appropriate preoperative planning, thus improving the global surgical outcome.

Level of Evidence V

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.



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Optimizing Patient Selection for Direct-to-Implant Immediate Breast Reconstruction Using Wise-Pattern Skin-Reducing Mastectomy in Large and Ptotic Breasts

Abstract

Background

Immediate breast reconstruction in large and ptotic breasts is challenging, often requiring skin-reducing procedures. The Wise-pattern skin-reducing mastectomy (WPSRM) technique provides reliable one-stage implant coverage using the pectoralis muscle and a de-epithelialized inferiorly based dermal flap. However, de-vascularization may result in mastectomy skin flap necrosis. We aimed to critically evaluate and isolate patients at high risk of complications using this procedure.

Methods

We retrospectively reviewed consecutive patients undergoing WPSRM by the senior author from January 2008 to December 2011. Data collected included patient demographics, breast cancer staging, smoking, preoperative radiation, chemotherapy, BMI, mastectomy weight, implant size and type. We analyzed their effect on complications, revisions and failure rate.

Results

Fifty-nine WPSRMs were performed in 39 patients with a minimum of 12-month follow-up. Complications occurred in 43.75% patients and 34.88% breasts. Multivariate statistical analysis revealed that age (p = 0.093) and BMI (p = 0.631) were not significant risk factors as opposed to previously published data. Mastectomy weight was significantly associated with major complications requiring secondary surgery (odds ratio per 100 g of breast tissue was 1.18; 95% CI 1.01–1.39; p = 0.036) as 90.5% of our complications occurred in those patients with mastectomy weight exceeding 700 g. Complications were reduced twofold when selecting a Becker adjustable implant over a silicone one for these higher mastectomy weights.

Conclusion

WPSRM was found to be associated with an increased complication rate in patients with high mastectomy weights and immediate reconstruction with silicone implants. We propose an algorithm offering better patient selection for this technique in immediate breast reconstruction.

Level of Evidence V

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.



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