Roles of amino acids in preventing and treating intestinal diseases: recent studies with pig models

Abstract

Animal models are needed to study and understand a human complex disease. Because of their similarities in anatomy, structure, physiology, and pathophysiology, the pig has proven its usefulness in studying human gastrointestinal diseases, such as inflammatory bowel disease, ischemia/reperfusion injury, diarrhea, and cancer. To understand the pathogenesis of these diseases, a number of experimental models generated in pigs are available, for example, through surgical manipulation, chemical induction, microbial infection, and genetic engineering. Our interests have been using amino acids as therapeutics in pig and human disease models. Amino acids not only play an important role in protein biosynthesis, but also exert significant physiological effects in regulating immunity, anti-oxidation, redox regulation, energy metabolism, signal transduction, and animal behavior. Recent studies in pigs have shown that specific dietary amino acids can improve intestinal integrity and function under normal and pathological conditions that protect the host from different diseases. In this review, we summarize several pig models in intestinal diseases and how amino acids can be used as therapeutics in treating pig and human diseases.

http://ift.tt/2s9cSaA

Annual Convention SFCR 2017, (French Spine Society annual congress) Lille Grand Palais 1st–3rd June, 2017

http://ift.tt/2rpBdw4

Learning patterns for discovering domain-oriented opinion words

Abstract

Sentiment analysis is a challenging task that attracted increasing interest during the last years. The availability of online data along with the business interest to keep up with consumer feedback generates a constant demand for online analysis of user-generated content. A key role to this task plays the utilization of domain-specific lexicons of opinion words that enables algorithms to classify short snippets of text into sentiment classes (positive, negative). This process is known as dictionary-based sentiment analysis. The related work tends to solve this lexicon identification problem by either exploiting a corpus and a thesaurus or by manually defining a set of patterns that will extract opinion words. In this work, we propose an unsupervised approach for discovering patterns that will extract domain-specific dictionary. Our approach (DidaxTo) utilizes opinion modifiers, sentiment consistency theories, polarity assignment graphs and pattern similarity metrics. The outcome is compared against lexicons extracted by the state-of-the-art approaches on a sentiment analysis task. Experiments on user reviews coming from a diverse set of products demonstrate the utility of the proposed method. An implementation of the proposed approach in an easy to use application for extracting opinion words from any domain and evaluate their quality is also presented.

http://ift.tt/2t0xTEG

A Response to Predictors of Heart Disease Knowledge Among Older and Younger Asian Indian Adults

http://ift.tt/2tkGIIM

Editorial

http://ift.tt/2s9lvCp

Modification of Cotton Fabrics with Silver Nanoparticles for Use in Conditioner Air to Minimize the Bioaerosol Concentration in Indoor Environments

Abstract

The pollution of the air and the monitoring of indoor air quality are receiving increasing attention worldwide, and many methodologies are now available to identify sources of pollution. However, there has been less work concerning the development of techniques to mitigate the effects of indoor air pollution. The aim of this study was to modify cotton fabrics with silver nanoparticles in order to use them in air conditioner filters. To achieve this goal, common fabrics purchased from commercial sources were evaluated in terms of their filtration properties (permeability, pressure drop, and collection efficiency) and were subsequently modified by impregnation with nanoparticles. This modification was achieved by immersion of the filters in nanoparticle suspensions. After drying the filter, collection of particulate matter was made in a toilet. The results showed that the filters impregnated with silver nanoparticles were able to significantly reduce the activity of microorganisms present in the airborne particulate matter, resulting in growth inhibition to the microorganisms which were retained (76.70%) and passed through (96.34%) the cotton filters.

http://ift.tt/2t04sm3

Increased expression of Bruton’s tyrosine kinase in peripheral blood is associated with lupus nephritis

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease manifested by multiorgan impairment. It is reported that B cells participate in the onset of SLE. Bruton's tyrosine kinase (Btk), as a downstream signaling molecule of B cell antigen receptor (BCR) signaling pathway, is involved in the development, activation, and survival of B cells. The aim of our study was to explore the specific role of Btk in lupus nephritis (LN). We determined the percentages of Btk+ B cells in peripheral blood mononuclear cells (PBMCs) from SLE patients by flow cytometry and analyzed the correlation between the percentage of Btk+ B cells and lupus-related clinical indexes. Immunohistochemistry was used to detect the Btk expression in kidney from LN patients and tumor surrounding tissues. Compared with controls, the frequency of Btk+ B cells in SLE patients was upregulated (p < 0.01), and it was significantly correlated with the SLE Disease Activity Index (SLEDAI) (p < 0.01), levels of plasma anti-dsDNA antibody (p < 0.05), the amount of 24-h urine protein (p < 0.05), and levels of plasma C3 (p < 0.05). The frequency of Btk+ B cells in the patients with LN was significantly higher than those without LN (p < 0.05). Although the Btk expression in glomerulus of LN patients was significantly increased compared with controls (p < 0.001), but it had no correlation with the renal pathology activity index, SLEDAI, or 24-h urine protein. In conclusion, the increased expression of Btk in peripheral blood was correlated with LN, indicating that it may be a therapeutic target for SLE.

http://ift.tt/2rZjpWZ

Cell-laden microgel prepared using a biocompatible aqueous two-phase strategy

Abstract

Microfluidic methods are frequently used to produce cell-laden microgels for various biomedical purposes. Such microfluidic methods generally employ oil-water systems. The poor distribution of crosslinking reagents in the oil phase limits the available gelation strategies. Extracting the microgel from the oil-phase also reduces its production efficiency. In this study, an aqueous two-phase system (ATPS) involving dextran (DEX) and polyethylene glycol (PEG) was used to prepare cell-laden microgel. This avoided the problems associated with an oil phase. The microgel precursor polymers and crosslinking reagents were dispersed in the DEX and PEG phases, respectively. The ultra-low interfacial tension of the ATPS hindered droplet formation. A co-flow microfluidic device was fabricated to overcome this problem. The device incorporated a square-wave-changing injection force, to improve the efficiency of droplet formation. The microgel precursor (including alginate and carboxymethyl cellulose derivatives possessing phenolic hydroxyl moieties) could be dispersed in the DEX solution at various concentrations. Uniform droplets were formed with controllable diameters, and were sequentially converted to microgel by horseradish peroxidase-catalyzed crosslinking. Cells were dispersed in the DEX phase with the microgel precursor polymer, and retained their high viability and proliferation in the resulting microgel. The solubility of gelatin derivatives in the DEX phase was low, but was sufficient to impart cell adhesion properties on the microgel.

http://ift.tt/2s8YIGA

Unusual location of cardiac hydatid cyst

Abstract

Hydatidosis is an epidemic disease in Tunisia. The cardiac presentation is rare. We report the case of a young woman, with history of liver and bilateral lung hydatidosis in childhood. She described a right chest pain and dyspnea. The computerized tomography scan confirmed the diagnosis of cardiac hydatid cyst with hydatid embolism in the lower right lung lobe. Exploration during surgery found a hydatid cyst located in the transverse sinus displacing the trunk of the pulmonary artery and the ascending aorta. We found a zone of weakness of the right pulmonary artery at its lower edge which was sutured. Adjuvant treatment based on Albendazol was prescribed. The diagnosis of cardiac hydatidosis is often difficult, and it is characterized by its potential seriousness, given the high risk of cyst rupture with pericardial dissemination or embolization in large vessels or cardiac cavities.

http://ift.tt/2rZ6J2y

Cocaine-Levamisole-Induced Vasculitis/Vasculopathy Syndrome

Abstract

Purpose of review

To understand the clinical spectrum of cocaine-levamisole-induced vasculitis. Worldwide recreational drug consumption is high among the adult population from various social strata. The use of cocaine with levamisole, a frequently added antiparasitic diluent, favors the manifestations of vasculitic lesions, especially in the skin.

Recent findings

New insights into immunological mechanisms involved in the pathogenesis of the disease. There are still many unknown aspects in the pathogenesis of this disease, such as the immune system interaction with p-ANCAs and the release of inflammatory NETs (neutrophil extracellular traps), which are the origin of auto-antigens and tissue damage, manifesting as vasculitic purpura on the skin. The clinical presentation constitutes a challenge for the clinician to be able to distinguish it from small-vessel vasculitides.

Summary

This paper intends to improve the understanding of this condition, exhibiting the broad clinical spectrum of local and systemic manifestations of cocaine-levamisole-induced vasculitis, to facilitate a timely diagnosis, in order to take corrective measures and avoid sequelae, along with tissue damage and the consequent deformities and permanent scars.

http://ift.tt/2smy0wt

Cocaine-Levamisole-Induced Vasculitis/Vasculopathy Syndrome

Abstract

Purpose of review

To understand the clinical spectrum of cocaine-levamisole-induced vasculitis. Worldwide recreational drug consumption is high among the adult population from various social strata. The use of cocaine with levamisole, a frequently added antiparasitic diluent, favors the manifestations of vasculitic lesions, especially in the skin.

Recent findings

New insights into immunological mechanisms involved in the pathogenesis of the disease. There are still many unknown aspects in the pathogenesis of this disease, such as the immune system interaction with p-ANCAs and the release of inflammatory NETs (neutrophil extracellular traps), which are the origin of auto-antigens and tissue damage, manifesting as vasculitic purpura on the skin. The clinical presentation constitutes a challenge for the clinician to be able to distinguish it from small-vessel vasculitides.

Summary

This paper intends to improve the understanding of this condition, exhibiting the broad clinical spectrum of local and systemic manifestations of cocaine-levamisole-induced vasculitis, to facilitate a timely diagnosis, in order to take corrective measures and avoid sequelae, along with tissue damage and the consequent deformities and permanent scars.

http://ift.tt/2smy0wt

Discordant sleep parameters among actigraphy, polysomnography, and perceived sleep in patients with sleep-disordered breathing in comparison with patients with chronic insomnia disorder

Abstract

Purpose

Although the clinical usefulness of actigraphy (ACT) in chronic insomnia disorder (CID) is extensively investigated, the evaluation on the utility of ACT in sleep-disordered breathing (SDB) is limited and the report of comparison with perceived sleep by patients and polysomnography (PSG) is scarce.

Methods

Thirty-six patients with SDB and 30 with CID underwent PSG and ACT, and they reported perceived sleep time and latency simultaneously. Sleep parameters (total sleep time [TST], sleep onset latency [SOL], sleep efficiency, and wakefulness after sleep onset [WASO]) were compared. Agreement among parameters was assessed with intraclass correlation coefficient (ICC) and 95% confidence interval.

Results

ACT overestimated TST and underestimated SOL and WASO relative to PSG in both groups. Perceived sleep was commonly undervalued relative to PSG or ACT. In post hoc analyses, perceived sleep was significantly shorter and SOL significantly longer compared to PSG and ACT in both groups. Perception of sleep time by PSG was significantly higher than perception by ACT. In the CID group, all sleep parameters were significantly correlated between ACT and PSG (ICC = 0.627–0.813). In the SDB group, only TST was significantly correlated (ICC = 0.804).

Conclusion

ACT is useful to monitor sleep and sleep quality in patients with CID. In patients with SDB, TST by ACT is reliable. However, ACT is insufficient to assess sleep quality due to its low agreement with PSG. Significantly lower sleep perception relative to PSG and ACT should be considered in the treatment of sleep disorders.

http://ift.tt/2slZtON

Prevention of parastomal hernia in the emergency setting

Abstract

Aim

This study assessed safety and efficacy associated with hernia prophylaxis using a retromuscular slowly resorbable synthetic mesh for stoma reinforcement.

Method

This was a cohort study with a historic reference group. The study took place in a high-volume surgical department. During a 2-year period (July 2012–July 2014), we included 109 patients undergoing emergency surgery with formation of ileostomy or colostomy. All patients received a retromuscular slowly resorbable synthetic mesh (TIGR®, Novus Scientific) at the stoma site. The reference group included 117 patients who underwent emergency stoma formation without a prophylactic mesh in the 2-year period prior to July 2012. The primary endpoint was effect on prevention of parastomal hernia within 1 year. Secondary endpoints were 30-day and 1-year complications including mortality.

Results

The operative field was contaminated or dirty in 48% of the procedures. Operative time was significantly longer in the mesh group. The cumulative incidences of parastomal hernia at 1 year for the control and the mesh group were 8 and 7% (p = 0.424), respectively. The postoperative 30-day and 1-year rate of complications, reoperations and mortality were not different between the two groups. No patients underwent removal of the mesh and no clinical mesh infections were seen.

Conclusion

Use of a resorbable synthetic mesh during emergency ostomy formation showed no significant preventive effect on formation of parastomal hernia after 1 year. Although surgery was often conducted in a severely contaminated field, the procedure was without significantly increased complication rate.

http://ift.tt/2rfRfnK

Cell source, differentiation, functional stimulation, and potential application of human thermogenic adipocytes in vitro

Abstract

Recent investigations have showed that the functional thermogenic adipocytes are present in both infants and adult humans. Accumulating evidence suggests that the coexistence of classical and inducible brown (brite) adipocytes in humans at adulthood and these adipocytes function to generate heat from energy resulting in reducing body fat and improving glucose metabolism. Human thermogenic adipocytes can be differentiated in vitro from stem cells, cell lines, or adipose stromal vascular fraction. Pre-activated human brite adipocytes in vitro can maintain their thermogenic function in normal or obese immunodeficient mice; therefore, they improve glucose homeostasis and reduce fat mass in obese animals. These key findings have opened a new door to use in vitro thermogenic adipocytes as a cell therapy to prevent obesity and related disorders. Thus, this paper intends to highlight our knowledge in aspects of in vitro human brite/brown adipocytes for the further studies.

http://ift.tt/2rp3djh

Stages of Change for Mammography Among Mexican Women and a Decisional Balance Comparison Across Countries

Abstract

An analysis of the adoption of secondary preventive behaviors is significant in regions with disparities in mammography use and breast cancer survival. Therefore, we determined the cognitive factors and the degree to which they differentiate stages of change in mammography among Mexican women. We also compared the decisional balance performance at Mexico, Switzerland, South Korea, and the USA. A cross-sectional study was designed for women in the stages of precontemplation (n = 240), contemplation (n = 243), action (n = 205), maintenance (n = 311), and relapse (n = 348). We only considered those ≥40 years with no cancer history. We measured the pros, cons, and self-efficacy, among other components. The decisional balance was estimated, and the result was transformed into T-scores. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with multinomial logistic regression using precontemplation as the reference group. The decisional balance distinguished stages partially: in contemplation, the OR was 1.26 (95%CI 1.08, 1.47) and in maintenance, 1.34 (95%CI 1.13, 1.59); in action and relapse, the statistical significance was marginal (p < 0.10). The decisional balance T-score performance registered variations among countries. Additionally, the effect of self-efficacy progressively ascended from contemplation to action and maintenance (OR = 1.29 [95%CI 1.05, 1.58], 1.53 [95%CI 1.20, 1.96], and 2.48 [95%CI 1.82, 3.39], respectively). Furthermore, risk perception and severity did not have an effect on stages of change among Mexican women. Recognition of what provokes action in a population is a key factor in the efficacy of screening programs. Variations among countries highlight the necessity for importance of investigating cognitive determinants for mammography in specific areas.

http://ift.tt/2roYCxi

Geographic distribution of phylogenetic species of the Fusarium graminearum species complex and their 8-ketotrichothecene chemotypes on wheat spikes in Iran

Abstract

Isolates of the Fusarium graminearum species complex (FGSC, n = 446) were collected from wheat spikes from northern and western regions of Iran with a history of Fusarium head blight (FHB) occurrences. The trichothecene mycotoxin genotypes/chemotypes, the associated phylogenetic species, and geographical distribution of these isolates were analyzed. Two phylogenetic species, Fusarium asiaticum and F. graminearum, were identified and were found to belong to sequence characterized amplified region (SCAR) groups V and I. Isolates from F. asiaticum species lineage 6 were within SCAR group V, whereas F. graminearum species lineage 7 were of SCAR group I. Of the 446 isolates assayed, 274 were F. asiaticum species predominantly of the nivalenol (NIV) genotype, while other isolates were either deoxynivalenol (DON) plus 3-acetyldeoxynivalenol (3-AcDON) or DON plus 15-acetyldeoxynivalenol (15-AcDON) genotype. Based on Tri7 gene sequences, a new subpopulation of 15-AcDON producers was observed among F. asiaticum strains in which 11-bp repeats were absent in the Tri7 sequences. The trichothecene chemotype was confirmed and quantified by high-performance liquid chromatography (HPLC) in 46 FGSC isolates. Isolates produced NIV (33.4–108.2 μg/g) and DON (64.7–473.6 μg/g) plus either 3-AcDON (51.4–142.4 μg/g) or 15-AcDON (24.1–99.3 μg/g). Among FGSC isolates, F. asiaticum produced the highest levels of trichothecenes. Using BIOCLIM based on the climate data of 20-year during 1994–2014, modelling geographical distribution of FGSC showed that F. asiaticum was restricted to warmer and humid areas with a median value of mean annual temperature of about 17.5 °C and annual rainfall of 658 mm, respectively (P < 0.05). In contrast, F. graminearum (only 15-AcDON producers) was restricted to cooler and drier areas, with a median value of the mean annual temperature of 14.4 °C and an annual rainfall of 384 mm, respectively (P < 0.05). Based on climate parameters at anthesis, the recorded distribution of F. graminearum and F. asiaticum was similar to that based on BIOCLIM parameters. Therefore, geographic differences on the wheat-growing areas in Iran have had a significant effect on distribution of FGSC and their trichothecene chemotypes.

http://ift.tt/2s8pY84

Histopathologic classification of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis: achievements, limitations, and perspectives

Abstract

Clinical and histological factors have been identified as predictors of early and late renal outcome in ANCA-associated vasculitides (AAV). The presence and severity of kidney involvement at diagnosis are associated with poor prognosis in both patient and renal survival. Histologic findings remain the gold standard for diagnosing patients with AAV. In order to quantify the extent of the morphological parameters in the renal biopsies and to identify the histopathological lesions that predict renal outcome, several scoring systems have been proposed to systematically assess kidney biopsies in AAV. Renal pathologists from an international working group proposed in 2010 a new histopathological classification. This scheme comprises four general categories, based on the predominance of the glomerular histological lesions: focal (≥50% normal glomeruli); crescentic (≥50% glomeruli with cellular crescents); mixed (<50% normal, <50% crescentic, <50% globally sclerotic glomeruli), and sclerotic (≥50% globally sclerotic glomeruli). This article reviews the background and the main studies that have validated the histopathologic classification of ANCA-associated glomerulonephritis, the conclusions derived from these studies, and the perspectives for the assessment of renal outcome in AAV.

http://ift.tt/2sm5TNU

N, S co-doped carbon dots with high quantum yield: tunable fluorescence in liquid/solid and extensible applications

Abstract

A set of the highly fluorescent N, S co-doped carbon dots (NSCDs) were prepared through one-step hydrothermal synthesis at different temperature with citric acid as the carbon source and cysteamine as the N, S source. The NSCDs synthesized at 200 °C show significant quantum yield (81%) due to its optimal structure. The structure of the NSCDs changed with varying degrees of carbonization/aromatization and different content of multifunctional groups of C=O, −NH₂, −OH, −SH, and N, S-aromatic heterocycte under different preparation temperatures, thus exhibiting tunable fluorescence. Especially, the obtained NSCDs exhibited a blue fluorescence in solution state and changed from strong blue to yellowish-green in its solid state under UV light as a result of the increase in preparation temperature. The as-prepared NSCDs can be used in selective detection of complex anions such as Cr₂O₇²⁻ and Fe(CN)₆³⁻, cell imaging, and preparation of fluorescent composite films.

Graphical Abstract

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http://ift.tt/2rpaG1F

Streptococcus pneumoniae antimicrobial resistance decreased in the Helsinki Metropolitan Area after routine 10-valent pneumococcal conjugate vaccination of infants in Finland

Abstract

Since the introduction of 10-valent pneumococcal conjugate vaccine (PCV10) into the Finnish national vaccination program in September 2010, the incidence of invasive pneumococcal disease in children has decreased steeply in Finland. We studied the antimicrobial susceptibility of invasive and non-invasive Streptococcus pneumoniae (pneumococcus) isolated in the Helsinki Metropolitan Area during 2009–2014. We divided the data into two age groups: isolates from patients <5 years old and ≥5 years old. We also studied the serotype distribution of invasive isolates and of a subset of non-invasive multidrug-resistant isolates. The invasive isolate numbers recovered from patients aged <5 years old declined from 33/228 (15%) in 2009 to 8/208 (4%) in 2014 (p < 0.001) and non-invasive isolate numbers declined during the same time period from 221/595 (37%) to 119/432 (28%) (p < 0.001). At the same time, the proportion of penicillin non-susceptible non-invasive isolates in this age group decreased from 25% (56/220) to 13% (15/119) (p = 0.001) and multidrug-resistant isolates from 22% (49/220) to 6% (7/119) (p < 0.001), respectively. The number of PCV10 serotype isolates also decreased among the serotyped multidrug-resistant non-invasive isolates. Among patients aged ≥5 years old, the isolate numbers did not show a similar decreasing trend compared to the younger group and, further, the number of non-PCV10 serotype isolates increased in invasive cases. To conclude, the antimicrobial non-susceptibility of pneumococcus has decreased markedly, especially among young patients (<5 years old), following PCV10 implementation in Finland.

http://ift.tt/2syscjH

Ligand exchange synthesis of organometallic Rh nanoparticles and application in explosive sensing

Abstract

Alkyne {phenyl acetylene (PA) and 9-ethynylphenanthrene (EPT)}-ligated Rh nanoparticles (1 and 2, respectively) with mean diameter of 1.5 ± 0.2 nm were synthesized via a facile and high-yield biphasic ligand exchange protocol using similar sized ethylene glycol (EG)-stabilized Rh nanoparticles as precursors (EG:Rh). The synthesized organometallic Rh nanoparticles were convincingly characterized using several spectroscopic and microscopic techniques, e.g., Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (¹H NMR), optical absorption spectroscopy (UV-Vis), photoluminescence spectroscopy (PL), powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), and transmission electron microscope (TEM). We propose that the syntheses mechanism relies on catalytic acetylenic (≡C–H, carbon–hydrogen) bond breaking by EG:Rh followed by strong metal–carbon bond formation with a vinyldiene (>C═C═M) motif. The obtained 1 and 2 showed luminescence property, which arises from ligand structure through intraparticle conjugation. Electron-rich phenanthrene-ligated Rh nanoparticles (2) showed good sensing performance for detection of electron deficient nitro-aromatic explosive molecules (NA) in solution phase through luminescence quenching method.

http://ift.tt/2spLHeH

Draining the Will to Make the Sale: The Impermissibility of Marketing by Ego-Depletion

Abstract

We argue that many modern marketing techniques are morally problematic because they take advantage of a phenomenon known as 'ego-depletion' according to which willpower is, similar to physical strength, a limited resource that can be depleted by predictable factors. We argue that this is impermissible for the same reason that spiking someone's drink to impair their judgment is impermissible.

http://ift.tt/2syzF2i

Potential impacts of climate change on extreme precipitation over four African coastal cities

Abstract

This study examines the impacts of climate change on characteristics of extreme precipitation events over four African coastal cities (Cape Town, Maputo, Lagos and Port Said) under two future climate scenarios (RCP4.5 and RCP8.5). Fourteen indices were used to characterise extreme precipitation and 16 multi-model simulation datasets from the Coordinated Regional Climate Downscaling Experiment (CORDEX) were analysed. The capability of the models to reproduce past characteristics of extreme precipitation over the cities was evaluated against four satellite datasets after quantifying the observation uncertainties over the cities. The models give realistic simulation of extreme precipitation characteristics over the cities, and in most cases, the magnitudes of the simulation biases are within the observation uncertainties. For both the RCP4.5 and RCP8.5 scenarios, the models project a decrease in wet days and an increase in dry spells over the four cities in the future. More intense daily precipitation is projected over Maputo, Lagos and Port Said. The intensity and frequency of extreme precipitation events are projected to increase over Lagos, but decrease over the other cities. A decrease in annual precipitation is projected over Cape Town, Maputo and Port Said, whilst an increase is projected over Lagos, where the water surplus from the more extreme precipitation events exceeds the deficit from the less wet days. A decrease in the number of widespread extreme events is indicated over all the cities. Wet-day percentile and all-day percentile methods signal opposite future changes in the extreme precipitation thresholds over the cities (except over Lagos). The results of this study may have application in managing the vulnerabilities of these coastal cities to extreme precipitation events under climate change.

http://ift.tt/2rovhmZ

Distribution of dipeptides in different protein structural classes: an effort to find new similarities

Abstract

Finding any regularity in the sequences of proteins and determining their correlation with structural features are of great interest for an understanding of molecular biology. We statistically analyzed the relative frequencies of all 400 possible dipeptides in a data set containing randomly selected proteins of different defined structural classes including all-alpha, all-beta, alpha + beta and alpha/beta families. We found that the distribution of dipeptides is not the same for different structural classes, and some of them are significantly far from a random distribution. A tendency of a given amino acid to localize in the first or second position of a dipeptide depending on the structural class of protein was also found. Interestingly, some amino acids may be substituted for each other in the first or second positions of specific dipeptides in each structural class. This finding apparently contrasts with the routine expectation from the viewpoint of amino acid properties, as classically understood.

http://ift.tt/2spC7IN

First-principles investigation for some physical properties of some fluoroperovskites compounds ABF 3 (A = K, Na; B = Mg, Zn)

Abstract

In this work, the structural, electronic and optical properties of fluoroperovskite ABF₃ (A = K, Na; B = Mg, Zn) were studied using two different approaches: the full-potential linearized augmented plane wave method and the pseudo-potential plane wave scheme in the frame of generalized gradient approximation features such as the lattice constant, bulk modulus and its pressure derivative are reported. The ground state properties of these compounds such as the equilibrium lattice constant and the bulk modulus are in good agreement with the experimental results. The first principles calculations were performed to study the electronic structures of ABF₃(A = K, Na; B = Mg, Zn) compounds and the results indicated that these four compounds are indirect band gap insulators. The optical properties are analysed and the source of some peaks in the spectra is discussed. Besides, the dielectric function, refractive index and extinction coefficient for radiation up to 25 eV have also been reported and discussed.

http://ift.tt/2spdVGr

Effect of confinement and stiffness on the conformational change of a semiflexible homopolymer chain

Abstract

We analyse the nature of the confinement of an infinitely long (and finite) linear semiflexible homo-polymer chain confined in between two geometrical constraints (A & B) under good solvent condition in two dimensions. The constraints are stair shaped impenetrable lines. A lattice model of fully directed self avoiding walk is used to list information of walks of the confined chain and the exact enumeration technique is used for the canonical ensemble of conformations of the confined chain to discuss equilibrium statistics of the chain. We calculate probability of finding the confined flexible chain segments with either one end of the chain lying on the constraint (i.e. polymer trains) or both the ends of the confined chain lying on the stair shaped constraints (polymer bridge and polymer arc). We have also calculated the force of confinement exerted by the constraints on to the chain or the force exerted by the chain on the geometrical constraints using grand canonical ensemble theory and discuss nature of variation of the force.

http://ift.tt/2sZ71ET

Direct Quantification of Solute Diffusivity in Agarose and Articular Cartilage Using Correlation Spectroscopy

Abstract

Articular cartilage is an avascular tissue; diffusive transport is critical for its homeostasis. While numerous techniques have been used to quantify diffusivity within porous, hydrated tissues and tissue engineered constructs, these techniques have suffered from issues regarding invasiveness and spatial resolution. In the present study, we implemented and compared two separate correlation spectroscopy techniques, fluorescence correlation spectroscopy (FCS) and raster image correlation spectroscopy (RICS), for the direct, and minimally-invasive quantification of fluorescent solute diffusion in agarose and articular cartilage. Specifically, we quantified the diffusional properties of fluorescein and Alexa Fluor 488-conjugated dextrans (3k and 10k) in aqueous solutions, agarose gels of varying concentration (i.e. 1, 3, 5%), and in different zones of juvenile bovine articular cartilage explants (i.e. superficial, middle, and deep). In agarose, properties of solute diffusion obtained via FCS and RICS were inversely related to molecule size, gel concentration, and applied strain. In cartilage, the diffusional properties of solutes were similarly dependent upon solute size, cartilage zone, and compressive strain; findings that agree with work utilizing other quantification techniques. In conclusion, this study established the utility of FCS and RICS as simple and minimally invasive techniques for quantifying microscale solute diffusivity within agarose constructs and articular cartilage explants.

http://ift.tt/2sYOSr3

Enhancement of Energy Production of the Intervertebral Disc by the Implantation of Polyurethane Mass Transfer Devices

Abstract

Insufficient nutrient supply has been suggested to be one of the etiologies for intervertebral disc (IVD) degeneration. We are investigating nutrient transport into the IVD as a potential treatment strategy for disc degeneration. Most cellular activities in the IVD (e.g., cell proliferation and extracellular matrix production) are mainly driven by adenosine-5′-triphosphate (ATP) which is the main energy currency. The objective of this study was to investigate the effect of increased mass transfer on ATP production in the IVD by the implantation of polyurethane (PU) mass transfer devices. In this study, the porcine functional spine units were used and divided into intact, device and surgical groups. For the device and surgical groups, two puncture holes were created bilaterally at the dorsal side of the annulus fibrosus (AF) region and the PU mass transfer devices were only implanted into the holes in the device group. Surgical groups were observed for the effects of placing the holes through the AF only. After 7 days of culture, the surgical group exhibited a significant reduction in the compressive stiffness and disc height compared to the intact and device groups, whereas no significant differences were found in compressive stiffness, disc height and cell viability between the intact and device groups. ATP, lactate and the proteoglycan contents in the device group were significantly higher than the intact group. These results indicated that the implantation of the PU mass transfer device can promote the nutrient transport and enhance energy production without compromising mechanical and cellular functions in the disc. These results also suggested that compromise to the AF has a negative impact on the IVD and must be addressed when treatment strategies are considered. The results of this study will help guide the development of potential strategies for disc degeneration.

http://ift.tt/2spzN4q

Risk factors for sciatica leading to hospitalization

Abstract

Purpose

To study the known or suspected risk factors for sciatica: Tallness, overweight, smoking, leisure-time physical exercise, self-reported health and occupation, and how they predict hospitalizations due to sciatica. Only a few cohort studies have previously focused on the risk factors for sciatica.

Methods

The 13,095 subjects, free from low back disorders at the baseline in 1973–1976 were followed up to the end of 2011 via the Care Register for Health Care. Along with an invitation to the health examination, a basic questionnaire concerning lifestyle factors was sent to participants. The outcome measure was incident sciatica leading to hospitalization.

Results

Altogether 702 incident sciatica cases occurred. Among men, the adjusted hazard ratio (HR) with 95% confidence interval (CI) was 2.57 (95% CI 1.47–4.50) in metal or machine work, and 1.44 (1.06–1.95) in other industrial work, compared to that in white-collar occupations. Among women, the corresponding risk estimates were 1.81 (1.18–2.78) for nurses and related occupations, 1.56 (1.05–2.31) for sales workers, and 1.46 (1.03–2.08) for industrial workers. Among men, physical exercise during leisure predicted a decrease in the risk of sciatica (0.74; 0.55–1.00); this association was significantly pronounced in white-collar occupations (0.38; 0.18–0.88). Among women, the association between body mass index and the risk of sciatica was only modest, but varied greatly between different occupations.

Conclusions

Physically demanding work is a strong risk factor for sciatica. Leisure-time physical activity seems to protect men against sciatica, while overweight is a risk factor among women. However, occupation substantially modifies these associations.

http://ift.tt/2tiAXLP

OX40 promotes obesity-induced adipose inflammation and insulin resistance

Abstract

Adaptive immunity plays a critical role in IR and T2DM development; however, the biological mechanisms linking T cell costimulation and glucose metabolism have not been fully elucidated. In this study, we demonstrated that the costimulatory molecule OX40 controls T cell activation and IR development. Inflammatory cell accumulation and enhanced proinflammatory gene expression, as well as high OX40 expression levels on CD4⁺ T cells, were observed in the adipose tissues of mice with diet-induced obesity. OX40-KO mice exhibited significantly less weight gain and lower fasting glucose levels than those of WT mice, without obvious adipose tissue inflammation. The effects of OX40 on IR are mechanistically linked to the promotion of T cell activation, Th1 cell differentiation and proliferation—as well as the attenuation of Treg suppressive activity and the enhancement of proinflammatory cytokine production—in adipose tissues. Furthermore, OX40 expression on T cells was positively associated with obesity in humans, suggesting that our findings are clinically relevant. In summary, our study revealed that OX40 in CD4⁺ T cells is crucial for adipose tissue inflammation and IR development. Therefore, the OX40 signaling pathway may be a new target for preventing or treating obesity-related IR and T2DM.

http://ift.tt/2sl4ZRy

Collective cell migration has distinct directionality and speed dynamics

Abstract

When a constraint is removed, confluent cells migrate directionally into the available space. How the migration directionality and speed increase are initiated at the leading edge and propagate into neighboring cells are not well understood. Using a quantitative visualization technique—Particle Image Velocimetry (PIV)—we revealed that migration directionality and speed had strikingly different dynamics. Migration directionality increases as a wave propagating from the leading edge into the cell sheet, while the increase in cell migration speed is maintained only at the leading edge. The overall directionality steadily increases with time as cells migrate into the cell-free space, but migration speed remains largely the same. A particle-based compass (PBC) model suggests cellular interplay (which depends on cell–cell distance) and migration speed are sufficient to capture the dynamics of migration directionality revealed experimentally. Extracellular Ca²⁺ regulated both migration speed and directionality, but in a significantly different way, suggested by the correlation between directionality and speed only in some dynamic ranges. Our experimental and modeling results reveal distinct directionality and speed dynamics in collective migration, and these factors can be regulated by extracellular Ca²⁺ through cellular interplay. Quantitative visualization using PIV and our PBC model thus provide a powerful approach to dissect the mechanisms of collective cell migration.

http://ift.tt/2tiOoem

Advances in the Development of Janus Kinase Inhibitors in Inflammatory Bowel Disease: Future Prospects

Abstract

Inflammatory bowel disease (IBD) is caused by a dysregulation of the immune system, inducing the production of proinflammatory cytokines and adhesion molecules. A better understanding of the mucosal immune response in IBD has led to the development of new drugs directed at inflammatory cytokines and leukocyte-trafficking molecules. Beyond tumor necrosis factor antagonists and anti-integrin molecules, which act by blocking the interaction between gut-specific lymphocytes and their receptor on vascular endothelium, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway represents a new target in IBD. JAK inhibitors are small molecules able to selectively target the activity of specific JAKs that play a role in signal transmission via interleukins. This review presents an overview of the role of the JAK/STAT signaling pathway and updated information for JAK molecules, which are promising drugs in IBD. Currently developed to treat ulcerative colitis and Crohn's disease, tofacitinib (in a phase III study) and filgotinib (in a phase II study), respectively, are the JAK inhibitors in the most advanced stage of development for IBD. However, the utility of, and adverse events associated with, these new drugs remain to be determined and clarified (in particular, the risk of herpes zoster infections), depending on the efficacy and tolerance determined from definitive studies. The availability of these drugs could enhance the therapeutic approach to IBD in the coming years, and reinforce the concept of personalized medicine for IBD patients.

http://ift.tt/2qXT4ta

Coffee consumption and risk of non-Hodgkin’s lymphoma: evidence from the Italian multicentre case–control study

Abstract

Purpose

Several investigations have analysed the association between coffee intake and risk of cancer. Contradictory results were reported by the studies conducted in non-Hodgkin's lymphomas (NHL) few of which report results according to main NHL subgroups. The present study is aimed at evaluating the association between coffee consumption and the risk of NHL by analysing data from a large Italian multicentre case–control study that included 1,418 interviewed cases (1,301 B cell and 117 T cell NHL), diagnosed between 1990 and 1993, and 1,774 population healthy controls.

Methods

The association was evaluated by standard logistic regression analysis. Odds ratio (OR) estimates were adjusted for gender, age, residence area, educational level, previous chemotherapy treatment, smoking habit and exposure to electromagnetic fields, radiation, pesticides and aromatic hydrocarbons.

Results

For all B cell lymphomas, an increased risk (OR 1.6, 95% CI 1.2–2.0) was observed in the highest exposure category (consumption >4 cups per day for at least 30 years), but without a clear dose–response trend. Subgroup analyses highlighted an increased risk for drinkers of at least four cups per day for follicular lymphoma (OR 2.0, 95% CI 1.2–3.4). The risk increased with years of exposure and was more elevated among current smokers.

Conclusions

Consumption of more than four cups of coffee per day enhances the risk of lymphoma, especially the follicular subtype. Further investigations based on large cohorts and accurate measures of exposure are needed to confirm the observed associations.

http://ift.tt/2skAlba

Using optogenetics to assess neuroendocrine modulation of heart rate in Drosophila melanogaster larvae

Abstract

The Drosophila melanogaster heart has become a principal model in which to study cardiac physiology and development. While the morphology of the heart in Drosophila and mammals is different, many of the molecular mechanisms that underlie heart development and function are similar and function can be assessed by similar physiological measurements, such as cardiac output, rate, and time in systole or diastole. Here, we have utilized an intact, optogenetic approach to assess the neural influence on heart rate in the third instar larvae. To simulate the release of modulators from the nervous system in response to environmental influences, we have directed expression of channel-rhodopsin variants to targeted neuronal populations to assess the role of these neural ensembles in directing release of modulators that may affect heart rate in vivo. Our observations show that the activation of targeted neurons, including cholinergic, dopaminergic, and serotonergic neurons, stimulate the release of cardioactive substances that increase heart rate after the initial activation at both room temperature and in a cold environment. This parallels previous studies suggesting these modulators play a crucial role in altering heart rate when applied to exposed hearts and adds to our understanding of chemical modulation of heart rate in intact Drosophila larvae.

http://ift.tt/2skGrZa

Targeting the PGD 2 /CRTH2/DP1 Signaling Pathway in Asthma and Allergic Disease: Current Status and Future Perspectives

Abstract

Prostaglandin D₂ (PGD₂) released by degranulating mast cells is believed to play a key role in orchestrating mechanisms of inflammation in allergies and asthma. The biological effects of PGD₂ are mediated by D-prostanoid (DP1), CRTH2 (DP2), and thromboxane prostanoid (TP) receptors. The CRTH2 receptor is involved in induction of migration and activation of T helper type 2 (Th₂) lymphocytes, eosinophils, and basophils; up-regulation of adhesion molecules; and promotion of pro-inflammatory Th₂-type cytokines (interleukin [IL]-4, 5, 13), whereas the DP receptor is associated with relaxation of smooth muscles, vasodilation, inhibition of cell migration, and apoptosis of eosinophils. A number of CRTH2/PGD₂ receptor antagonists have been investigated in asthma and allergic diseases. The CRTH2 antagonist (OC000459) or dual CRTH2 and TP receptor antagonist (ramatroban) were effective in reducing eosinophilia, nasal mucosal swelling, and clinical symptoms of allergic rhinitis, with the latter drug registered for clinical use in this indication. OC000459 and setipiprant reduced the late but not early phase of response in an allergen challenge in atopic asthmatics. In persistent asthma, some molecules induced limited improvement in lung function, quality of life, and asthma symptoms (OC000459, BI671800), but in other trials with AMG 853 and AZ1981 these findings were not confirmed. The clear discrepancy between animal studies and clinical efficacy of CRTH2 antagonism in allergic rhinitis, and lack of efficacy in a general cohort of asthmatics, highlight the issue of patient phenotyping. There is no doubt that the PGD₂/CATH2/DP1 pathway plays a key role in allergic inflammation and further studies with selective or combined antagonisms in well defined cohorts of patients are needed.

http://ift.tt/2rrZSLe

Comparing Strategies for Providing Child and Youth Mental Health Care Services in Canada, the United States, and The Netherlands

Abstract

This paper reviews how child and youth mental health care services in Canada, the United States, and the Netherlands are organized and financed in order to identify systems and individual-level factors that may inhibit or discourage access to treatment for youth with mental health problems, such as public or private health insurance coverage, out-of-pocket expenses, and referral requirements for specialized mental health care services. Pathways to care for treatment of mental health problems among children and youth are conceptualized and discussed in reference to health insurance coverage and access to specialty services. We outline reforms to the organization of health care that have been introduced in recent years, and the basket of services covered by public and private insurance schemes. We conclude with a discussion of country-level opportunities to enhance access to child and youth mental health services using existing health policy levers in Canada, the United States and the Netherlands.

http://ift.tt/2spvc2e

Transanal Hartmann’s colostomy reversal assisted by laparoscopy: outcomes of the first 10 patients

Abstract

Introduction

Restoration of intestinal continuity after Hartmann's procedure is a technically difficult surgery associated with significant morbidity and mortality. This study presents the short-term results of a new approach: a transanal Hartmann's colostomy reversal assisted by laparoscopy.

Method

This is a retrospective analysis of data collected in one tertiary hospital, from October 2013 to November 2015.

Results

During the study period, there were ten cases of transanal Hartmann's reversal. Reasons for Hartmann's procedure were: complicated diverticulitis (4), anastomotic leak (3), and recto-sigmoid cancer (3). Rectal stump length was 10.4 ± 4.5 cm. Reconstruction was achieved in all patients. One low colorectal anastomosis was hand-sewn, the other 9 were stapled. Mean operative time was 204 ± 65 min. Diverting loop ileostomies were created in five patients and all were closed during the following year. One case required hand-assistance but there was no conversion to open surgery. Iatrogenic laparoscopic enterotomies occurred in four patients and all were repaired primarily without consequences. Three patients had a total of four post-operative complications: ileus (2), abdominal abscess and wound infection (1). None required reoperation. Mean length of stay was 7.2 ± 4.3 days. One required readmission.

Conclusion

A transanal Hartmann's reversal assisted by laparoscopy is a new approach for a difficult surgery. It has the potential to be an additional tool in the case of hostile pelvises or with a rectal stump difficult to identify. The surgery remains challenging and indications need to be clarified.

http://ift.tt/2rntxKA

Anti-allodynic action of the disease-modifying anti-rheumatic drug iguratimod in a rat model of neuropathic pain

Abstract

Objective

Patients with rheumatoid arthritis experience nociceptive as well as neuropathic pain. The effect of iguratimod (IGU), a disease-modifying anti-rheumatic drug, on neuropathic pain in a rat model of chronic constriction injury (CCI) was examined in this study.

Methods

CCI was induced by making four ligations on the left sciatic nerve. Rats with stable signs of static allodynia were selected 2 weeks after the surgery and drug treatments were started (day 0). The test drugs were orally administered once daily for 15 days. The threshold of mechanical pain response in the hind paw was evaluated by the von Frey hair test in a blinded manner. To observe histological changes in the spinal cord, the L4 region was subjected to immunohistochemical analysis for the detection of microglial cells.

Results

IGU showed an anti-allodynic effect on CCI-induced neuropathic pain at days 6 and 14, but not at 90 min after the first administration of IGU. This effect of IGU was observed until day 21. Furthermore, IGU decreased the number of Iba-1-positive cells, which had been increased at the ipsilateral side of the dorsal horn by CCI.

Conclusions

These results suggest that IGU suppresses neuropathic pain via a different mechanism from that of current therapeutics.

http://ift.tt/2thIaeW

Antidepressant Actions of Ketamine Mediated by the Mechanistic Target of Rapamycin, Nitric Oxide, and Rheb

Abstract

The weeks/months it takes for traditional antidepressants to act pose an obstacle in the management of depression. Ketamine's prompt and sustained antidepressant effects constitute a major advance. Multiple studies implicate glutamatergic signaling to protein synthesis machinery and synapse formation in ketamine's antidepressant effects. Here we review evidence linking ketamine to glutamate receptor subtypes and protein homeostasis. We describe a signaling cascade wherein nitric oxide drives the formation of a ternary protein complex comprised of glyceraldehyde 3-phosphate dehydrogenase, seven in absentia homolog 1, and Ras homolog enriched in brain downstream of the glutamate N-methyl-D-aspartate receptor. Seven in absentia homolog 1 ubiquitylates and degrades Ras homolog enriched in brain leading to inhibition of mechanistic target of rapamycin. Ketamine inhibits this molecular cascade leading to activation of mechanistic target of rapamycin and, in turn, to antidepressant actions.

http://ift.tt/2rrShML

Long acting systemic HIV pre-exposure prophylaxis: an examination of the field

Abstract

Oral pre-exposure prophylaxis for the prevention of HIV-1 transmission (HIV PrEP) has been widely successful as demonstrated by a number of clinical trials. However, studies have also demonstrated the need for patients to tightly adhere to oral dosing regimens in order to maintain protective plasma and tissue concentrations. This is especially true for women, who experience less forgiveness from dose skipping than men in clinical trials of HIV PrEP. There is increasing interest in long-acting (LA), user-independent forms of HIV PrEP that could overcome this adherence challenge. These technologies have taken multiple forms including LA injectables and implantables. Phase III efficacy trials are ongoing for a LA injectable candidate for HIV PrEP. This review will focus on the design considerations for both LA injectable and implantable platforms for HIV PrEP. Additionally, we have summarized the existing LA technologies currently in clinical and pre-clinical studies for HIV PrEP as well as other technologies that have been applied to HIV PrEP and contraceptives. Our discussion will focus on the potential application of these technologies in low resource areas, and their use in global women's health.

http://ift.tt/2rnLLvn

Methylation markers differentiate thyroid cancer from benign nodules

Abstract

Purpose

The incidence of thyroid cancer (TC) is increasing. Cytology by itself cannot distinguish TC from some benign nodules especially in certain subtypes of TC. Our immediate goal is to identify DNA methylation markers for early detection of TC and to molecularly differentiate TC subtypes from benign nodules.

Methods

Promoter methylation status of 21 candidate genes was examined on formalin-fixed paraffin-embedded tissue (FFPE) utilizing quantitative methylation-specific polymerase chain reaction (QMSP) in a retrospective cohort of 329 patients (56% white, 29% African American, 61% female) comprising 71 normal thyroid, 83 benign nodules [follicular adenomas (FA)], 90 follicular TC (FTC) and 85 papillary TC (PTC). All genes were analyzed individually (Kruskal–Wallis and Wilcoxon rank sum tests) and in combination (logistic regression models) to identify genes whose methylation levels might best separate groups.

Results

Combination gene panels TPO and UCHL1 (ROC = 0.607, sensitivity 78%) discriminated FTC from FA, and RASSF1 and TPO (ROC = 0.881, sensitivity 78%) discriminated FTC from normal. Methylation of TSHR distinguished PTC from FTC (ROC = 0.701, sensitivity 84%) and PTC from FA (ROC = 0.685, sensitivity 70%). The six gene panel of TIMP3, RARB2, SERPINB5, RASSF1, TPO and TSHR, which differentiates PTC from normal thyroid, had the best combination sensitivity (91%) and specificity (81%) of the panels addressing discrimination of cancer tissue.

Conclusions

Aberrant gene methylation used in combination panels may be useful clinically in differentiating FTC and PTC from benign nodules. If confirmed in additional studies, these findings could help reduce the over diagnosis of thyroid cancer and surgeries related to over diagnosis.

http://ift.tt/2sk7NPb

Midostaurin: First Global Approval

Abstract

Midostaurin (Rydapt^®) is a multikinase inhibitor being developed by Novartis Pharmaceuticals. In April 2017, midostaurin was approved in the USA for the treatment of adult patients with newly diagnosed, FMS-like tyrosine kinase 3 (FLT3) mutation-positive acute myeloid leukaemia (AML) [in combination with standard cytarabine and daunorubicin induction, and cytarabine consolidation], or aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated haematological neoplasm (SM-AHN) or mast cell leukaemia (MCL) [collectively known as advanced SM]. The article summarizes the milestones in the development of midostaurin leading to this first global approval.

http://ift.tt/2rrzykL

Biologic therapies for refractory juvenile dermatomyositis: five years of experience of the Childhood Arthritis and Rheumatology Research Alliance in North America

Abstract

Background

The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011–2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA).

Methods

The JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011–2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013–2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting.

Results

One hundred and five of a potential 231 pediatric rheumatologists (42%) responded to the first survey in 2012. Thirty-five of 90 had never used a biologic for Juvenile DM at that time. Fifty-five of 91 (denominators vary) had used biologics for JDM in their practice with 32%, 5%, and 4% using rituximab, etanercept, and infliximab, respectively, and 17% having used more than one of the three drugs. Ten percent used a biologic as monotherapy, 19% a biologic in combination with methotrexate (mtx), 52% a biologic in combination with mtx and corticosteroids, 42% a combination of a biologic, mtx, corticosteroids (steroids), and an immunosuppressive drug, and 43% a combination of a biologic, IVIG and mtx. The results of the second survey supported these findings in considerably more detail with multiple combinations of drugs used with biologics and supported the use of rituximab, abatacept, anti-TNFα drugs, and tocilizumab in that order. One hundred percent recommended that CARRA continue studying biologics for JDM. The CARRA meeting survey in 2016 again supported the study and use of these four biologic drug groups.

Conclusions

Our CARRA JDM biologic work group developed and performed three surveys demonstrating that pediatric rheumatologists in North America have been using multiple biologics for refractory JDM in numerous scenarios from 2011 to 2016. These survey results and our consensus meetings determined our choice of four biologic therapies (rituximab, abatacept, tocilizumab and anti-TNFα drugs) to consider for refractory JDM treatment when indicated and to evaluate for comparative effectiveness and safety in the future.

Significance and Innovations

• This is the first report that provides a substantial clinical experience of a large group of pediatric rheumatologists with biologics for refractory JDM over five years.

• This experience with biologic therapies for refractory JDM may aid pediatric rheumatologists in the current treatment of these children and form a basis for further clinical research into the comparative effectiveness and safety of biologics for refractory JDM.

http://ift.tt/2rWTBe5

To be disordered or not to be disordered: is that still a question for proteins in the cell?

Abstract

There is ample evidence that many proteins or regions of proteins lack a well-defined folded structure under native-like conditions. These are called intrinsically disordered proteins (IDPs) or intrinsically disordered regions (IDRs). Whether this intrinsic disorder is also their main structural characteristic in living cells has been a matter of intense debate. The structural analysis of IDPs became an important challenge also because of their involvement in a plethora of human diseases, which made IDPs attractive targets for therapeutic development. Therefore, biophysical approaches are increasingly being employed to probe the structural and dynamical state of proteins, not only in isolation in a test tube, but also in a complex biological environment and even within intact cells. Here, we survey direct and indirect evidence that structural disorder is in fact the physiological state of many proteins in the proteome. The paradigmatic case of α-synuclein is used to illustrate the controversial nature of this topic.

http://ift.tt/2sjIsoj

Assessing the Feasibility and Effectiveness of an App in Improving Knowledge on Oral Cancer—an Interventional Study

Abstract

Although current oral health care initiatives have proved to be quite successful, a great number of individuals are unaware of how their choice of daily activities compromises their oral health. That is why newer technologies like WhatsApp can definitely serve as a platform to communicate dental advice, thereby strengthening the bridge between health and technology. The objective of the study was to assess the effectiveness of WhatsApp as a tool for providing health education on tobacco and oral cancer as compared to the conventional health education via PowerPoint. The study was a cluster randomized controlled trial, single-center study. The students of 18–24 years of age with WhatsApp application active in their mobile phones were included. Four classes with 182 students were randomly divided into intervention and control groups. Control group received health education on oral cancer using a PowerPoint presentation weekly, for a total of 4 weeks. Intervention group received health education through WhatsApp messaging thrice a week for 4 weeks. Pre- and post-health education knowledge scores were assessed using a questionnaire and compared using unpaired and paired two-sample t tests. Statistically significant increase in knowledge scores was seen in both groups, with highly significant improvement in the intervention group (p value = 0.00). Intergroup comparison showed no significant difference in knowledge scores at baseline, but a significant difference in post intervention knowledge scores (t = -15.05 p<0.001) WhatsApp can be a more effective tool for providing dental education on tobacco and oral cancer as compared to conventional audio-visual aids.

http://ift.tt/2sxjbro

The Intercostal Chest Drain—the ‘C S’ Way…!

http://ift.tt/2skaoZs

Progression of function and pain relief as indicators for returning to sports after arthroscopic isolated type II SLAP repair—a prospective study

Abstract

Background

One of the currently used surgical techniques in isolated type II SLAP lesions is arthroscopic SLAP repair. Postoperatively, patients tend to suffer from a prolonged period of pain and are restricted in their sports activities for at least 6 months. The aim of this study was to prospectively evaluate the clinical outcome as well as the postoperative course of pain after arthroscopic type II SLAP repair.

Methods

Outcome measures were assessed using the Individual Relative Constant Score (CS_indiv), the American Shoulder and Elbow Surgeons (ASES) Score, the Visual Analogue Scale (VAS), and the Short Form 36 (SF-36). Data were collected preoperatively, as well as at 3, 6, 12 and >24 months postoperatively.

Results

Eleven patients with an average age of 31.8 years (range: 22.8-49.8 years) underwent arthroscopic repair of isolated type II SLAP lesions. Mean follow-up time was 41.9 months (range: 36.1–48.4 months). 6 months after surgery, there was a statistically significant improvement of function according to the CS_indiv (p = 0.004), the ASES Score (p = 0.006), and the SF-36 subscale "physical functioning" (p = 0.014) and a statistically significant decrease of pain according to the VAS (p = 0.007) and the SF-36 subscale "bodily pain" (p = 0.022) compared to preoperative levels.

Conclusions

Arthroscopic repair of isolated type II SLAP lesions with suture anchors leads to a satisfactory functional outcome and return to pre-injury sports levels, with delayed, but significant pain relief observed 6 months after surgery. Thus, a return to sports should not be allowed earlier than 6 months after surgery, when patients have reached pain-free function and recovered strength.

Trial registration

Researchregistry1761 (UIN).

http://ift.tt/2rWqfww

Management of unresectable, locally advanced pancreatic adenocarcinoma

Abstract

The diagnosis of unresectable locally advanced pancreatic adenocarcinoma (LAPC) requires confirmation, through imaging tests, of the unfeasibility of achieving a complete surgical resection, in the absence of metastatic spread. The increase in overall survival (OS), together with an appropriate symptom management is the therapeutic target in LAPC, maintaining an acceptable quality of life and, if possible, increasing the time until the appearance of metastasis. Chemoradiation (CRT) improves OS compared to best support treatment or radiotherapy (RT) but with greater toxicity. No significant increase in OS has been achieved with CRT when compared to chemotherapy (QT) alone in patients without disease progression after four months of treatment with QT. However, a significantly better local control, that is, a significant increase in the time to disease progression was associated with this approach. The greater effectiveness of the schemes FOLFIRINOX and gemcitabine (Gem) + Nab-paclitaxel compared to gemcitabine alone, has been extrapolated from metastatic disease to LAPC, representing a possible alternative for patients with good performance status (ECOG 0–1). In the absence of randomized clinical trials, Gem is the standard treatment in LAPC. If disease control is achieved after 4–6 cycles of QT, the use of CRT for consolidation can be considered an option vs QT treatment maintenance. Capecitabine has a better toxicity profile and effectiveness compared to gemcitabine as a radiosensitizer. After local progression, and without evidence of metastases, treatment with RT or CRT, in selected patients, can support to maintain the regional disease control.

http://ift.tt/2sxdA4f

Neoadjuvant treatment for borderline and resectable pancreatic ductal adenocarcinoma

Abstract

Nowadays and given the improvement in response rate with the new schemes of treatment with chemotherapy, the interest in neoadjuvant treatment for pancreatic ductal adenocarcinoma, allowing the early application of systemic therapies, has also increased. However, treatment selection fundamentally depends on decisions taken by multidisciplinary committees due to the absence of randomized trials on this indication and because the available evidence is based primarily on small studies. The present manuscript tries to establish recommendations based on the available evidence and expert opinion to correctly select the indication, the type of treatment, as well as its duration and how to correctly follow-up patients during treatment with chemotherapy.

http://ift.tt/2rehnQ7

Diagnostic value of arterial blood gas lactate concentration in the different forms of mesenteric ischemia

Abstract

Purpose

The role of serum lactate measurement in patients with intestinal ischemia still remains unclear. The aim of this study was to prospectively evaluate the diagnostic performance of arterial blood gas lactate concentrations in the patients with acute mesenteric ischemia and its different forms.

Methods

All the patients reporting abdominal pain associated with risk factors for mesenteric ischemia underwent arterial blood gas and contrast enhanced abdominal computer tomography (CT).

Results

At CT, 201 patients (70.7%) showed a nonischemic disease (group 1) and 83 patients (29.2%) showed findings of mesenteric ischemia. Out of these, 35 patients (42.1%) showed bowel ischemia secondary to non vascular causes (group 2) and 48 (57.8%) had a vascular intestinal ischemia (group 3). Out of these, 20 showed small bowel arterial occlusion (group 3a), 13 a small bowel nonocclusive ischemia (group 3b), 7 a venous small bowel occlusion (group 3c) and 8 showed isolated colonic ischemia (group 3d). The median lactate serum level was significantly higher in patients with vascular ischemia if compared with patients with nonischemic disease and secondary mesenteric ischemia (p < 0.0001; Kruskal–Wallis test). The areas under ROC curves for the lactate serum levels in the groups 2, 3, 3a, 3b, 3c and 3d were, respectively, 0.61, 0.85, 0.93, 0.93, 0.68 and 0.67.

Conclusions

Arterial blood gas lactate levels seem to show good diagnostic accuracy in diagnosing small bowel arterial and nonocclusive ischemia and poor accuracy in diagnosing secondary mesenteric ischemia, small bowel venous ischemia and ischemic colitis.

http://ift.tt/2s6W8Rq

Why Social Science is Biological Science

Abstract

The social sciences need to take seriously their status as divisions of biology. As such they need to recognize the central role of Darwinian processes in all the phenomena they seek to explain. An argument for this claim is formulated in terms of a small number of relatively precise premises that focus on the nature of the kinds and taxonomies of all the social sciences. The analytical taxonomies of all the social sciences are shown to require a Darwinian approach to human affairs, though not a nativist or genetically driven theory by any means. Non-genetic Darwinian processes have the fundamental role on all human affairs. I expound a general account of how Darwinian processes operate in human affairs by selecting for strategies and sets of strategies individuals and groups employ. I conclude by showing how a great deal of social science can be organized in accordance with Tinbergen's approach to biological inquiry, an approach required by the fact that the social sciences are all divisions of biology, and in particular the studies of one particular biological species.

http://ift.tt/2rehF9y

Induction and Natural Necessities

Abstract

Some philosophers who believe that there are necessary connections in nature take it that an advantage of their commitment is that the problem of induction is solved. This paper aims to offer a comprehensive refutation of the arguments necessitarians use to show that if natural necessities are posited, then there is no problem of induction. In section 2, two models of natural necessity are presented. The "Contingent Natural Necessity" section examines David Armstrong's explanationist 'solution' to the problem of induction. The "Natural Necessity and IBE" section looks in detail into the claim that natural necessity is the best explanation of observed regularity. The "Dispositional Essentialism to the Rescue?" section moves on to Brian Ellis's dispositional essentialist 'solution'. The "Sankey's Helping Hand" section examines Howard Sankey's attempt to blend dispositional essentialism and explanationism.

http://ift.tt/2sxtcoi

Bio-logging, new technologies to study conservation physiology on the move: a case study on annual survival of Himalayan vultures

Abstract

Bio-logging, the on-animal deployment of miniaturised electronic data recorders, allows for the study of location, body position, and physiology of individuals throughout their ontogeny. For terrestrial animals, 1 Hz GPS-position, 3D-body acceleration, and ambient temperature provide standard data to link to the physiology of life histories. Environmental context is added at ever finer scales using remote sensing earth observation data. Here we showcase the use of such bio-logging approaches in a conservation physiology study on endangered Himalayan vultures (Gyps himalayensis). We determine environmental, behavioural, and physiological causes of survival in immature birds that roam from wintering sites in India, Bhutan, and Nepal towards summer areas in Tibet and Mongolia. Five of 18 immature griffons died during one year. Individuals that died had failed to migrate sufficiently far northward (>1500 km) in spring. Individuals likely died if they flew against headwinds from the north or were less able to find thermal updrafts. Surviving individuals migrated to cold and dry areas with low population density. We highlight flight experience, long distance movements, and remote places with low human population as factors critical for the survival of Himalayan vultures. High-resolution bio-logging studies can advance conservation management by pinpointing where and why migratory animals have problems and die.

http://ift.tt/2sjKBQQ

Letter to the Editor concerning “Spinal metallosis: a systematic review” by Goldenberg Y, Tee JW, Salinas-La Rosa CM, Murphy M (Eur Spine J; 2016, 25:1467–1473)

http://ift.tt/2sjYxdM

Comparison of inter- and intra-observer reliability among the three classification systems for cervical spinal canal stenosis

Abstract

Purpose

The aim is to analyze the agreement between different types of physicians in terms of the inter-observer and intra-observer reliability in addition to the agreement between the experienced and non-experienced physicians with respect to three different classification systems for diagnosis of cervical spinal canal stenosis.

Methods

Total nine doctors including experienced group of three doctors and non-experienced group of six doctors classified the patients according to three different classification in an independent, blinded manner using magnetic resonance imaging (MRI) to diagnose cervical canal stenosis. MRI slice included sagittal plane (midline cut) and an image slice from each horizontal plane that penetrated the right center of each disk (C3–4, C4–5, C5–6, and C6–7) was made by PPT format.

Results

For the inter-observer reliability, Vaccaro et al.'s classification system showed the excellent reproducibility, followed by Muhle et al. and Kang et al. All three classification systems showed excellent reproducibility and substantial agreement in terms of the intra-observer reliability.

Conclusions

All three classification systems showed excellent reproducibility and also displayed a substantial agreement. The classification system used by Vaccaro et al. was proven to be a method with substantial agreement both in the experienced group and the non-experienced group. It can be a useful classification system for simplifying communication among all physicians.

http://ift.tt/2thLdDQ

Effective Rheology of Two-Phase Flow in Three-Dimensional Porous Media: Experiment and Simulation

Abstract

We present an experimental and numerical study of immiscible two-phase flow of Newtonian fluids in three-dimensional (3D) porous media to find the relationship between the volumetric flow rate (Q) and the total pressure difference ( \(\Delta P\) ) in the steady state. We show that in the regime where capillary forces compete with the viscous forces, the distribution of capillary barriers at the interfaces effectively creates a yield threshold ( \(P_t\) ), making the fluids reminiscent of a Bingham viscoplastic fluid in the porous medium. In this regime, Q depends quadratically on an excess pressure drop ( \(\Delta P-P_t\) ). While increasing the flow rate, there is a transition, beyond which the overall flow is Newtonian and the relationship is linear. In our experiments, we build a model porous medium using a column of glass beads transporting two fluids, deionized water and air. For the numerical study, reconstructed 3D pore networks from real core samples are considered and the transport of wetting and non-wetting fluids through the network is modeled by tracking the fluid interfaces with time. We find agreement between our numerical and experimental results. Our results match with the mean-field results reported earlier.

http://ift.tt/2solhtU

Particle Flow Code Method-Based Meso-scale Identification for Seepage Failure of Soil Levee

Abstract

The long-term action of internal and external factors leads constantly to seepage failures of soil levee engineering such as soil flow failure and piping failure. It is very disadvantageous to the service safety of levee engineering. Most of disastrous accidents are induced directly or indirectly by seepage. It has been known that the water–soil interaction with particle migration determines the occurrence and development of seepage failure. In this paper, a particle flow code (PFC)-based approach is introduced to implement the numerical simulation for seepage behavior in soil levee and investigate the meso-scale seepage failures. Firstly, according to the granular properties and particle migration characteristics of soil levee, an implementation process is presented to construct the meso-scale soil particle model and analyze the levee failure. Then, considering the coupling action of soil and water, a numerical method combining PFC with computation fluid dynamics is developed to simulate the seepage failure of soil levee. The corresponding criteria on seepage failures of soil levee are given. Lastly, one actual levee engineering is taken as an example. The movements of soil and water in the soil flow and piping processes are investigated with meso-scale soil particle model of selected levee. The meso-scale mechanism of seepage failures is analyzed, and the seepage stability is evaluated. It is indicated that the proposed PFC-based approach can fulfill the real-time observation for the movement status of soil particles and water during seepage failure of soil levee. The seepage stability identification with the introduced meso-scale criteria shows good agreement with the experimental result.

http://ift.tt/2sXEKyL

Cotransport of Graphene Oxide Nanoparticles and Kaolinite Colloids in Porous Media

Abstract

This study examines the influence of pH and ionic strength ( \(I_{\mathrm{S}}\) ) on the cotransport of graphene oxide (GO) nanoparticles and kaolinite (KGa-1b) colloids. Several flowthrough experiments were conducted in water-saturated columns, packed with either glass beads or quartz sand, in order to determine the transport behavior of GO and KGa-1b independently, as well as the cotransport behavior of GO together with KGa-1b. Various water chemistry conditions ( \(\hbox {pH}=4, 7, 10\) and \(I_{\mathrm{S}}=7, 12, 27\,\hbox {mM}\) ) were considered. Collision efficiencies were calculated using the classical colloid filtration theory. Interaction energy profiles between GO nanoparticles or KGa-1b colloids and glass beads or quartz sand were constructed for the various experimental conditions, by using measured zeta potentials and applying the classical Derjaguin–Landau–Verwey–Overbeek theory. The cotransport experimental breakthrough data suggested that by lowering the pH, the retention of GO nanoparticles is enhanced, due to a possible increase in heteroaggregation between GO nanoparticles and KGa-1b colloids. Also, by increasing the \(I_{\mathrm{S}}\) values, the retention of GO nanoparticles was slightly increased. The mass recovery of GO nanoparticles was reduced, and the transport of GO nanoparticles was retarded in the presence of KGa-1b colloids. Furthermore, the retention of GO nanoparticles was greater for columns packed with quartz sand than glass beads.

http://ift.tt/2sotChk

Understanding Oil and Gas Flow Mechanisms in Shale Reservoirs Using SLD–PR Transport Model

Abstract

More and more attention has been paid to the oil and gas flow mechanisms in shale reservoirs. The solid–fluid interaction becomes significant when the pores are in the nanoscale. The interaction changes the fluid's physical properties and leads to different flow mechanisms in shale reservoirs from those in conventional reservoirs. By using a Simplified Local Density–Peng Robinson transport model, we consider the density and viscosity profiles, which result from solid–fluid interaction. Gas rarefaction effect is negligible at high pressure, so we assume it is viscous flow. Considering the density- and viscosity-changing effects, we proposed a slit permeability model. The velocity profiles are obtained by this newly established model. This proposed model is validated by matching the density profile and velocity profile from molecular dynamic simulation. Then, the effects of pressure and pore size on gas and oil flow mechanisms are also studied in this work. The results show that both gas and oil exhibit enhanced flow rates in nanopores. Gas-phase flow in nanopores is dominated by the density-changing effect (adsorption), while the oil-phase flow is mainly controlled by the viscosity-changing effect. Both gas and oil permeability quickly decrease to the Darcy permeability when the slit aperture becomes large. The results reported in this work are representative and should significantly help us understand the mechanisms of oil and gas flow in shale reservoirs.

http://ift.tt/2sXCnf9

Risk assessment and outcomes of vasoplegia after cardiac surgery

Abstract

Objective

The aim of this study was to analyze risk factors and outcomes of vasoplegia after cardiac surgery based on our experience with almost 2000 cardiac operations performed at our institution.

Methods

We retrospectively analyzed patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) between 2011 and 2013. Data were available for a total of 1992 patients. We defined vasoplegia as hypotension with persistently low systemic vascular resistance (<800 dyn/s/cm) and preserved Cardiac Index (>2.5).

Results

The rate of vasoplegia in our cohort was 20.3% (n = 405). The incidences of mild, moderate, and severe vasoplegia were 13.2, 5.7, and 1.5%, respectively. Factors that increased risk of vasoplegia included valve operations, heart transplants, dialysis-dependent renal failure, age >65, diuretic therapy, and recent myocardial infarction. B blocker therapy was protective against vasoplegia.

Conclusion

Vasoplegic syndrome is still a frequently occurring adverse event following cardiac surgery. In high risk patients for vasoplegia, it may be sensible to proceed with preoperative volume loading (instead of diuresis), initiation of low dose vasopressin therapy if needed, and attempting to up titrate beta-blocker therapy.

http://ift.tt/2rdODXQ

Erratum zu: Perioperative cerebrospinal fluid drainage for the prevention of spinal ischemia after endovascular aortic repair

http://ift.tt/2thkc3z

Placental and maternal serum activin A in spontaneous and induced labor in late-term pregnancy

Abstract

Purpose

Feto-placental unit represents an important source of activin A, a member of transforming growth factors-β involved in the mechanisms of labor. No evidences are available on activin A in pregnancies beyond 41 weeks of gestation, where induction of labor is often required. The present study aimed to evaluate activin A maternal serum levels and placental mRNA expression in term and late-term pregnancy, with spontaneous or induced labor, and its possible role to predict the response to labor induction.

Methods

Maternal serum samples and placental specimens were collected from women with singleton pregnancy admitted for either term spontaneous labor (n = 23) or induction of labor for late-term pregnancy (n = 41), to evaluate activin A serum levels and placental mRNA expression. Univariate and multivariate analyses on activin A serum levels, maternal clinical parameters, and cervical length were conducted in women undergoing induction of labor.

Results

Maternal serum activin A levels and placental activin A mRNA expression in late-term pregnancies were significantly higher than at term. Late-term pregnancies who did not respond to induction of labor showed significantly lower levels of activin A compared to responders. The combination of serum activin A and cervical length achieved a sensitivity of 100% and a specificity of 93.55% for the prediction of successful induction.

Conclusion

Late-term pregnancy is characterized by hyperexpression of placental activin A and increased maternal activin A secretion. By combining maternal serum activin A levels with cervical length, a good predictive model for the response to induction of labor was elaborated.

http://ift.tt/2sjmFgp

Production of paclitaxel with anticancer activity by two local fungal endophytes, Aspergillus fumigatus and Alternaria tenuissima

Abstract

Among 60 fungal endophytes isolated from twigs, bark, and mature leaves of different plant species, two fungal isolates named TXD105 and TER995 were capable of producing paclitaxel in amounts of up to 84.41 and 37.92 μg L⁻¹, respectively. Based on macroscopic and microscopic characteristics, ITS1–5.8S–ITS2 rDNA sequence, and phylogenetic characteristic analysis, the two respective isolates were identified as Aspergillus fumigatus and Alternaria tenuissima. In the effort to increase paclitaxel magnitude by the two fungal strains, several fermentation conditions including selection of the proper fermentation medium, agitation rate, incubation temperature, fermentation period, medium pH, medium volume, and inoculum nature (size and age of inoculum) were tried. Fermentation process carried out in M1D medium (pH 6.0) and maintained at 120 rpm for 10 days and at 25 °C using 4% (v/v) inoculum of 5-day-old culture stimulated the highest paclitaxel production to attain 307.03 μg L⁻¹ by the A. fumigatus strain. In the case of the A. tenuissima strain, fermentation conditions conducted in flask basal medium (pH 6.0) and maintained at 120 rpm for 14 days and at 25 °C using 8% (v/v) inoculum of 7-day-old culture were found the most favorable to attain the highest paclitaxel production of 124.32 μg L⁻¹. Using the MTT-based assay, fungal paclitaxel significantly inhibited the proliferation of five different cancer cell lines with 50% inhibitory concentration values varied from 3.04 to 14.8 μg mL⁻¹. Hence, these findings offer new and alternate sources with excellent biotechnological potential for paclitaxel production by fungal fermentation.

http://ift.tt/2rWblX8

18 F-fluorothymidine PET imaging in gliomas: an update

Abstract

Brain neoplasms constitute a group of tumors with discrete differentiation grades, and therefore, course of disease and prognosis. Magnetic resonance imaging (MRI) remains the gold standard method for the investigation of central nervous system tumors. However, MRI suffers certain limitations, especially if radiation therapy or chemotherapy has been previously applied. On the other hand, given the development of newer radiopharmaceuticals, positron emission tomography (PET) aims to a better investigation of brain tumors, assisting in the clinical management of the patients. In the present review, the potential contribution of radiolabeled fluorothymidine (FLT) imaging for the evaluation of brain tumors will be discussed. In particular, we will present the role of FLT-PET imaging in the depiction of well and poorly differentiated lesions, the assessment of patient prognosis and treatment response, and the recognition of disease recurrence. Moreover, related semi-quantitative and kinetic parameters will be discussed.

http://ift.tt/2rqVPza

Growth and remodeling with application to abdominal aortic aneurysms

Abstract

In this paper, we apply a mixture theory of growth and remodeling to study the formation and dilatation of abdominal aortic aneurysms. We adapt the continuum theory of mixtures to formalize the processes of production and removal of constituents from a loaded body. Specifically, we consider a mixture of elastin and collagen fibers which endow the material with anisotropic properties. An evolving recruitment variable defines the intermediate configuration from which the elastic stretch of collagen is measured. General formulations of the equations governing homeostatic state and aneurysm development are provided. In the homeostatic state, the idealized geometry of the aorta is a thick-walled tube subject to constant internal pressure and axial stretch. The formation of an aneurysm induces an increase of mass locally achieved via production of new material that exceeds the removal of old material. The combined effects of loss of elastin, degradation of existing and deposition of new collagen, as well as fiber remodeling results in a continuous enlargement of the aneurysm bulge. The numerical method makes use of a purposely written material subroutine, called UMAT, which is based on the constitutive formulation provided in the paper. Numerical results based on patient-based material parameters are illustrated.

http://ift.tt/2sXwiPK

Auto-trilevel versus bilevel positive airway pressure ventilation for hypercapnic overlap syndrome patients

Abstract

Purpose

Although bilevel positive airway pressure (Bilevel PAP) therapy is usually used for overlap syndrome (OS), there is still a portion of OS patients in whom Bilevel PAP therapy could not simultaneously eliminate residual apnea events and hypercapnia. The current study was expected to explore whether auto-trilevel positive airway pressure (auto-trilevel PAP) therapy with auto-adjusting end expiratory positive airway pressure (EEPAP) can serve as a better alternative for these patients.

Methods

From January of 2014 to June of 2016, 32 hypercapnic OS patients with stable chronic obstructive pulmonary diseases (COPD) and moderate-to-severe obstructive sleep apnea syndrome (OSAS) were recruited. Three variable modes of positive airway pressure (PAP) from the ventilator (Prisma25ST, Weinmann Inc., Germany) were applicated for 8 h per night. We performed the design of each mode at each night with an interval of two nights with no PAP treatment as a washout period among different modes. In Bilevel-1 mode (Bilevel-1), the expiratory positive airway pressure (EPAP) delivered from Bilevel PAP was always set as the lowest PAP for abolishment of snoring. For each patient, the inspiratory positive airway pressure (IPAP) was constantly set the same as the minimal pressure for keeping end-tidal CO₂ (ETCO₂) ≤45 mmHg for all three modes. However, the EPAP issued by Bilevel PAP in Bilevel-2 mode (Bilevel-2) was kept 3 cmH₂O higher than that in Bilevel-1. In auto-trilevel mode (auto-trilevel) with auto-trilevel PAP, the initial part of EPAP was fixed at the same PAP as that in Bilevel-1 while the EEPAP was automatically regulated to rise at a range of ≤4 cmH₂O based on nasal airflow wave changes. Comparisons were made for parameters before and during or following treatment as well as among different PAP therapy modes. The following parameters were compared such as nocturnal apnea hypopnea index (AHI), minimal SpO₂ (minSpO₂), arousal index, sleep structure and efficiency, morning PaCO₂, and daytime Epworth Sleepiness Scale (ESS).

Results

Compared with the parameters before PAP therapies, during each mode of PAP treatment, significant reduction was detected in nocturnal AHI, arousal index, morning PaCO₂, and daytime ESS while significant elevation was revealed in nocturnal minSpO₂ and sleep efficiency (all P < 0.01). Comparison among three PAP modes indicated that under the same IPAP, the auto-trilevel PAP mode could result in the lowest arousal index, daytime ESS, and the highest sleep efficiency. Compared with Bilevel-1, it was detected that (a) AHI was lower but minSpO₂ was higher in both Bilevel-2 and auto-trilevel (all P < 0.05) and (b) morning PaCO₂ showed no statistical difference from that in auto-trilevel but displayed higher in Bilevel-2 (P < 0.05). Compared with Bilevel-2, in auto-trilevel, both AHI and minSpO₂ showed no obvious changes (all P > 0.05) except with a lower morning PaCO₂ (P < 0.05).

Conclusion

Auto-trilevel PAP therapy was superior over conventional Bilevel PAP therapy for hypercapnic OS patients with their OSAS moderate to severe, since auto-trilevel PAP was more efficacious in synchronous elimination of residual obstructive apnea events and CO₂ retention as well as in obtaining a better sleep quality and milder daytime drowsiness.

http://ift.tt/2th9iL8

Daytime napping and risk of type 2 diabetes: a meta-analysis of prospective studies

Abstract

Purpose

Prospective studies reported inconsistent findings on the relationship between daytime napping and risk of type 2 diabetes (T2D). Categorized and dose-response meta-analyses were performed to quantify this relation.

Methods

Potentially eligible studies were identified by searching PubMed and Embase databases. Dose-response effects were assessed by the generalized least squares trend estimation and study-specific summary relative risks (RRs) with 95% confidence intervals (CIs) were computed with a random-effects model.

Results

Seven prospective studies including one US, four European, and two Chinese cohorts involving 249,077 participants and 13,237 cases of T2D were included. The overall analyses showed a 17% increased risk of T2D when comparing habitual nappers with non-nappers (RR = 1.17, 95% CI 1.08–1.27). By region, the summary RR was 1.21 (95% CI 1.17–1.26), 1.15 (95% CI 1.03–1.30) and 1.23 (95% CI 0.87–1.73) for the US, European, and Chinese studies, respectively. Limiting to five studies that excluded subjects with known major chronic disorders yielded a summary RR of 1.16 (95% CI 1.03–1.30). A dose-response analysis suggested an 11% (95% CI 7–16%) increased T2D risk for each increment in daytime napping of 30 min/day and, despite no evidence for nonlinearity (P _nonlinearity = 0.65), the increased risk of T2D for short nap (<50 min/day) was dominated by the US study.

Conclusions

This meta-analysis suggests that daytime napping is associated with an increased risk of T2D. Given the limited number of cohorts and inconsistency in terms of methodological and population characteristics across these cohorts, residual confounders and/or reverse causality cannot be fully addressed, and our findings should be interpreted with great caution. Future well-designed prospective studies are still warranted.

http://ift.tt/2sjtgrl

Diagnosis and staging of pancreatic ductal adenocarcinoma

Abstract

The management of pancreatic ductal adenocarcinoma (PDAC) is a major public health concern worldwide. Currently, most PDAC patients are diagnosed in advanced stages. The signs and symptoms of the disease, except for jaundice, are non-specific. Thus, the current challenge is to identify earlier those individuals for whom specific screening tools and specific treatments would be beneficial. On the basis of the recommendations of the group of experts of multiple medical specialties of the GALLgo Project, the patients with PDAC should be managed by a multidisciplinary team to assess the personal and family history, the best diagnostic and staging procedures and consider all important aspects for treatment decisions. In this article, the group of experts proposes strategies to shorten the diagnosis times in PDAC patients.

http://ift.tt/2rVX24Q

MRI-guided radiotherapy for head and neck cancer: initial clinical experience

Abstract

Purpose

To report a single-institutional experience with the use of magnetic resonance imaging (MRI)-guided radiotherapy for cancers of the head and neck.

Materials and methods

Between October 2014 and October 2016, 18 patients with newly diagnosed cancers of the head and neck were prospectively enrolled on an institutional registry trial investigating the feasibility and efficacy of external-beam radiotherapy delivered using on-board MRI. All patients had biopsy-proven evidence of malignancy, measurable disease, and the ability to provide consent. None had previously received any treatment. Median dose was 70 Gy (range 54–70 Gy). MRI scans were obtained as part of an image-guided registration protocol for alignment prior to and during each treatment. Concurrent chemotherapy was administered to 14 patients (78%). Patient-reported outcomes were assessed using the University of Washington quality of life instrument.

Results

Seventeen of 18 patients completed the planned intensity-modulated radiotherapy (IMRT) treatment of which 15 (83%) had a complete response and 2 (11%) had a partial response based on initial post-therapy positron emission tomography (PET) at 3 months. The 1-year estimates of progression-free survival, overall survival, and local–regional control were 95, 96, and 95%, respectively. There were no treatment-related fatalities. The incidence of grade 3+ acute toxicity was 44%. The proportion of patients rating their health-related quality of life as "very good" or "outstanding" at 6 months and 1 year after completion of radiation therapy was 60 and 70%, respectively.

Conclusions

MRI-guided radiotherapy achieves clinical outcomes comparable to contemporary series reporting on IMRT for head and neck cancer.

http://ift.tt/2rr52Hp

Supportive care in pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with poorest prognosis and represents the third leading cause of cancer-related deaths in Western countries. Despite advances in diagnostic procedures and treatment, diagnosis is made in most cases when the disease is locally advanced or metastatic. Supportive care aims to improve symptoms, reduce hospital admission rates, and preserve quality of life. Proper symptomatic management is critical to allow administration of chemotherapy and radiotherapy. Symptomatic management should be accomplished in a multidisciplinary fashion. Its primary aims include relief of biliary or duodenal obstruction, prevention and/or treatment of thromboembolic disease, and control cancer-related pain. Nutritional support and optimal replacement therapy in patients with endocrine and/or exocrine insufficiency, is mandatory. This manuscript highlights the most significant problems faced when caring for patients with advanced PDAC and provides an evidence-based approach to symptomatic management.

http://ift.tt/2rWocsw

The influence of vitamin C on the interaction between acute mental stress and endothelial function

Abstract

Purpose

To determine whether orally administered vitamin C attenuates expected mental stress-induced reductions in brachial artery endothelial function as measured by flow-mediated dilation (FMD).

Methods

Fifteen men (21 ± 2 years) were given 1000 mg of vitamin C or placebo over two visits in a randomized, double-blinded, within-subject design. Acute mental stress was induced using the Trier Social Stress Test (TSST). Saliva samples for cortisol determination and FMD measures were obtained at baseline, pre-TSST, and 30 and 90-min post-TSST. An additional saliva sample was obtained immediately post-TSST. Cardiovascular stress reactivity was characterized by changes in heart rate (HR) and mean arterial pressure (MAP).

Results

A significant stress response was elicited by the TSST in both conditions [MAP, HR, and salivary cortisol increased (p < 0.001)]. Overall FMD did not differ pre- vs. post-stress (time: p = 0.631) and there was no effect of vitamin C (condition: p = 0.792) (interaction between time and condition, p = 0.573). However, there was a correlation between cortisol reactivity and changes in FMD from pre- to post-stress in the placebo condition (r ² = 0.66, p < 0.001) that was abolished in the vitamin C condition (r ² = 0.02, p = 0.612).

Conclusion

Acute mental stress did not impair endothelial function, and vitamin C disrupted the relationship between cortisol reactivity and changes in FMD post-stress. This suggests that acute mental stress does not universally impair endothelial function and that reactive oxygen species signaling may influence the interaction between FMD and stress responses.

http://ift.tt/2so2y1M

Pathophysiology of Gastric NETs: Role of Gastrin and Menin

Abstract

Purpose of review

Neuroendocrine tumors (NETs) were initially identified as a separate entity in the early 1900s as a unique malignancy that secretes bioactive amines. GI-NETs are the most frequent type and represent a unique subset of NETs, because at least 75% of these tumors represent gastrin stimulation of the enterochromaffin-like cell located in the body of the stomach.

The purpose of this review is to understand the specific role of gastrin in the generation of Gastric NETs (G-NETs).

Recent findings

We review here the origin of enterochromaffin cells gut and the role of hypergastrinemia in gastric enteroendocrine tumorigenesis. We describe generation of the first genetically engineered mouse model of gastrin-driven G-NETs that mimics the human phenotype. The common mechanism observed in both the hypergastrinemic mouse model and human carcinoids is translocation of the cyclin-dependent inhibitor p27^kip to the cytoplasm and its subsequent degradation by the proteasome.

Summary

Therapies that block degradation of p27^kip, the CCKBR2 gastrin receptor, or gastrin peptide are likely to facilitate treatment.

http://ift.tt/2rWcmOS