Image Sharing in Radiology—A Primer

Publication date: Available online 3 January 2017
Source:Academic Radiology
Author(s): Arindam R. Chatterjee, Seth Stalcup, Arjun Sharma, T. Shawn Sato, Pushpender Gupta, Yueh Z. Lee, Christopher Malone, Morgan McBee, Elise L. Hotaling, Akash P. Kansagra
By virtue of its information technology-oriented infrastructure, the specialty of radiology is uniquely positioned to be at the forefront of efforts to promote data sharing across the healthcare enterprise, including particularly image sharing. The potential benefits of image sharing for clinical, research, and educational applications in radiology are immense. In this work, our group—the Association of University Radiologists (AUR) Radiology Research Alliance Task Force on Image Sharing—reviews the benefits of implementing image sharing capability, introduces current image sharing platforms and details their unique requirements, and presents emerging platforms that may see greater adoption in the future. By understanding this complex ecosystem of image sharing solutions, radiologists can become important advocates for the successful implementation of these powerful image sharing resources.



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Promoting Bioengineered Tooth Innervation Using Nanostructured and Hybrid Scaffolds

Publication date: Available online 3 January 2017
Source:Acta Biomaterialia
Author(s): S. Kuchler-Bopp, A. Larrea, L. Petry, Y. Idoux-Gillet, V. Sebastian, A. Ferrandon, P. Schwinté, M. Arruebo, N. Benkirane-Jessel
The innervation of teeth mediated by axons originating from the trigeminal ganglia is essential for their function and protection. Immunosuppressive therapy using Cyclosporine A (CsA) was found to accelerate the innervation of transplanted tissues and particularly that of bioengineered teeth. To avoid the CsA side effects, we report in this study the preparation of CsA loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles, their embedding on polycaprolactone (PCL)-based scaffolds and their possible use as templates for the innervation of bioengineered teeth. This PCL scaffold, approved by the FDA and capable of mimicking the extracellular matrix, was obtained by electrospinning and decorated with CsA-loaded PLGA nanoparticles to allow a local sustained action of this immunosuppressive drug. Dental re-associations were co-implanted with a trigeminal ganglion on functionalized scaffolds containing PLGA and PLGA/Cyclosporine in adult ICR mice during 2 weeks. Histological analyses showed that the designed scaffolds did not alter the teeth development after in vivo implantation. The study of the innervation of the dental re-associations by indirect immunofluorescence and transmission electron microscopy (TEM), showed that 88.4% of the regenerated teeth were innervated when using the CsA-loaded PLGA scaffold. The development of active implants thus allows their potential use in the context of dental engineering.Statement of significanceTooth innervation is essential for their function and protection and this can be promoted in vivo using polymeric scaffolds functionalized with immunosuppressive drug-loaded nanoparticles. Immunosuppressive therapy using biodegradable nanoparticles loaded with Cyclosporine A was found to accelerate the innervation of bioengineered teeth after two weeks of implantation.

Graphical abstract

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Indentation Across Interfaces Between Stiff and Compliant Tissues

Publication date: Available online 4 January 2017
Source:Acta Biomaterialia
Author(s): Oliver E. Armitage, Michelle L. Oyen
Bone–tendon, bone–ligament and bone–cartilage junctions are multi-tissue interfaces that connect materials that differ by two orders of magnitude in mechanical properties, via gradual variations in mineral content and matrix composition. These sites mediate load transfer between highly dissimilar materials and are consequently a primary site of injury during orthopedic failure. Given the large incidence rate and the lack of suitable surgical solutions for their regeneration or repair, characterization of their natural structure and subsequent replication through tissue engineering is important. Here, we evaluate the ability and accuracy of instrumented indentation to characterize the mechanical properties of both biological tissues and engineered scaffolds with interfaces between materials that contain significant changes in mechanical properties. In this study, finite element simulations and reference samples are developed that characterize how accurately indentation measures the modulus of a material as it varies with distance across a continuous interface between dissimilar tissues with multiple orders of magnitude difference in properties. Finite element simulations accurately predicted discrepancies between the modulus function across an interface observed by indentation and the true modulus function of the material and hence allow us to understand the limits of instrumented indentation as a technique for quantifying gradual changes in material properties. It was found that in order to accurately investigate mechanical property variations in tissues with significant modulus heterogeneity the indenter size should be less than 10 percent of the expected length scale of the modulus variations.

Graphical abstract

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Hypothyroidism associated with nivolumab treatment of unresectable malignant melanoma

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Synthesis and activity of the salicylic acid ester of bakuchiol in psoriasis-surrogate keratinocytes and skin substitutes

Summary

Background

Topical retinoids are effective in retarding skin ageing and restoring homeostasis in skin conditions such as psoriasis. However their adverse effects (AEs), which include irritation (retinoid dermatitis), photosensitivity and teratogenicity, limit their use and patient compliance. Development of retinoid analogues with minimal AEs would allow a broader and more compliant use.

Aim

To synthesise a novel molecule, bakuchiol salicylate (bakusylan), with a modulatory gene expression profile similar to retinoids, using as reference three prescription retinoids: tretinoin, tazarotene and adapalene.

Methods

We hypothesized that because bakuchiol salicylate has a structure entirely different from existing retinoids, there would be at least a partial uncoupling of AEs from the skin-normalizing activity of this retinoid. This hypothesis was tested at the transcriptional level in psoriatic cytokine-treated cultures of keratinocytes and organotypic skin substitutes, using DNA microarrays and custom PCR arrays.

Results

Evaluation of the gene expression profile of bakuchiol salicylate revealed elimination of several components of the retinoid-like proinflammatory response and teratogenic signature, without a substantial loss of normalizing potential. A possible mechanism of action, consisting of keratinocyte desensitization to psoriatic cytokine signalling through inhibition of the signal transducer and regulator of transcription (STAT)1/3/interferon inflammatory signal transduction axis was also identified.

Conclusion

Bipartite materials obtained by merging two skin-active entities with specific, complementary bioactivities, such as bakuchiol and salicylic acid, may yield a new class of functional retinoids.

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Dabigatran in the management of livedoid vasculopathy

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Segmental lichen aureus in infancy

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Morphoea with prominent plasma cell endoneuritis

Summary

Morphoea (localized scleroderma) is a cutaneous inflammatory condition characterized by the development of indurated and discoloured plaques. The histological features of morphoea typically include a superficial and deep perivascular and periadnexal chronic inflammatory infiltrate associated with variable degrees of dermal and/or subcutaneous sclerosis. The infiltrate is typically composed of lymphocytes, macrophages and conspicuous plasma cells. The early stages of morphoea may have a very prominent inflammatory infiltrate associated with subtle sclerosis. In addition, the inflammatory infiltrate may show a perineural and rarely intraneural distribution. We report two cases of morphoea that histologically showed plasma cell endoneuritis associated with subtle dermal sclerosis. These two cases highlight the potential for diagnostic confusion with infectious and inflammatory diseases, particularly leprosy and lupus.

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Use of nicotinamide in dermatology

Summary

Nicotinamide (niacinamide) is the water-soluble, amide form of vitamin B3. We review the evidence underlying the use of nicotinamide for various dermatological indications, including nonmelanoma cancer prophylaxis, blistering disorders, acne vulgaris and cosmetic indications, and speculate upon its future role in dermatological practice.

http://ift.tt/2hQWp7C

Use of optical coherence tomography for the diagnosis of preclinical lesions of circumscribed palmar hypokeratosis

Summary

Circumscribed hypokeratosis of palms and soles is a rare dermatosis, usually affecting women. Diagnosis is mainly based on the clinical characteristics, including the clinical appearance and anatomical site of the skin lesions and on the demographic features of the affected patients, usually middle-aged to elderly women. Skin biopsy may be performed to confirm clinical diagnosis. Optical coherence tomography (OCT) is a technique that has been undergone substantial development in dermatology in recent years, and its use in clinical practice has been growing progressively. Several dermatological conditions have been studied with this tool, but to our knowledge, it has not been used to investigate this form of hypokeratosis. We report a case of circumscribed palmar hypokeratosis for which diagnosis was confirmed by OCT, which was performed as the patient was reluctant to undergo skin biopsy because of its invasiveness. We highlight the potential use of OCT in obtaining a virtual skin biopsy to confirm clinical diagnosis and identify preclinical skin lesions amenable to early treatment.

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Dermal hyperneury: a rare but increasingly recognized entity

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Innate immunity in cutaneous melanoma

Summary

The skin immune system is composed of a vast network of immune cells, including lymphocytes, macrophages, neutrophils, dendritic cells and Langerhans cells, which not only are involved in inflammatory responses but also contribute to homeostatic function and may participate in the various steps of carcinogenesis. Many studies support the notion that innate immunity has a key role in the development, growth and prognosis of cutaneous malignant melanoma (MM), through the release of pro- and/or anti-inflammatory cytokines and tumour growth factors. The tumour environment in a major subset of cutaneous MM shows evidence of a T cell-infiltrated phenotype, but there is less known about the presence and the phenotype of other immune system cells. Response to immunotherapy is largely correlated with the presence of T cells in the tumour microenvironment, while the regulation exerted by stromal components such as macrophages and mast cells has been less investigated. In the current report, we review the recent literature, focusing our attention on the role of macrophages, dendritic cells, mast cells and natural killer cells in orchestrating MM progression, to better understand tumour immunobiology. The identification of new therapeutic targets and the application of approaches aimed at modulating crosstalk between immune and tumour cells, could have a crucial impact on immunotherapy and result in better clinical outcome. We hope this review will be helpful in cutaneous MM research.

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Development of abdominal wall endometriosis in a region distant from a caesarean section scar

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Giant prolactinomas: Multi-modal approach to achieve tumor control

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Comparative genomic analysis of the genus Enterococcus

Publication date: Available online 3 January 2017
Source:Microbiological Research
Author(s): Zhi Zhong, Wenyi Zhang, Yuqin Song, Wenjun Liu, Haiyan Xu, Xiaoxia Xi, Bilige Menghe, Heping Zhang, Zhihong Sun
As important lactic acid bacteria, Enterococcus species are widely used in the production of fermented food. However, as some strains of Enterococcus are opportunistic pathogens, their safety has not been generally accepted. In recent years, a large number of new species have been described and classified within the genus Enterococcus, so a better understanding of the genetic relationships and evolution of Enterococcus species is needed. In this study, the genomes of 29 type strains of Enterococcus species were sequenced. In combination with eight complete genome sequences from the Genbank database, the whole genomes of 37 strains of Enterococcus were comparatively analyzed. The average length of Enterococcus genomes was 3.20 Mb and the average GC content was 37.99%. The core- and pan- genomes were defined based on the genomes of the 37 strains of Enterococcus. The core-genome contained 605 genes, a large proportion of which were associated with carbohydrate metabolism, protein metabolism, DNA and RNA metabolism. The phylogenetic tree showed that habitat is very important in the evolution of Enterococcus. The genetic relationships were closer in strains that come from similar habitats. According to the topology of the time tree, we found that humans and mammals may be the original hosts of Enterococcus, and then species from humans and mammals made a host-shift to plants, birds, food and other environments. However, it was just a evolutionary scenario, and more data and efforts were needed to prove this postulation. The comparative genomic analysis provided a snapshot of the evolution and genetic diversity of the genus Enterococcus, which paves the way for follow-up studies on its taxonomy and functional genomics.



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Everolimus Alleviates Obstructive Hydrocephalus Due to Subependymal Giant Cell Astrocytomas

Publication date: Available online 3 January 2017
Source:Pediatric Neurology
Author(s): Romina Moavero, Andrea Carai, Angela Mastronuzzi, Sara Marciano, Federica Graziola, Federico Vigevano, Paolo Curatolo
Background and purposeSubependymal giant cell astrocytomas (SEGA) are low-grade tumors affecting up to 20% of patients with tuberous sclerosis complex (TSC). Early neurosurgical resection has been the only standard treatment until few years ago when the better understanding of the molecular pathogenesis of TSC led to the use of mTOR inhibitors. Surgical resection of SEGA is still considered as the first line treatment in individuals with symptomatic hydrocephalus and intratumoral hemorrhage. We report a clinical series of 4 patients presenting symptomatic or asymptomatic hydrocephalus who were successfully treated with everolimus.Main findingsAll patients presented a clinically significant response to everolimus and an early shrinkage with improvement of ventricular dilatation. Everolimus appeared to be well tolerated in all subjects.ConclusionOur clinical series demonstrate a possible expanding indication for mTOR inhibition in TSC, which can be considered in patients with asymptomatic hydrocephalus or even when the symptoms already appeared. It offers a significant therapeutic alternative to individuals that once would have undergone immediate surgery. Everolimus can allow to postpone neurosurgical resection, making it elective with an overall lower risk.



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Fetal Magnetic Resonance Imaging of Fetus With Zika Virus Infection

Publication date: Available online 3 January 2017
Source:Pediatric Neurology
Author(s): Beuy Joob, Viroj Wiwanitkit




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Schwartz-Jampel Syndrome

Publication date: Available online 4 January 2017
Source:Pediatric Neurology
Author(s): Natasha Mathur, Partha S. Ghosh




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Evaluation of cortical local field potential diffusion in stereotactic electro-encephalography recordings: A glimpse on white matter signal

Publication date: 15 February 2017
Source:NeuroImage, Volume 147
Author(s): Manuel R. Mercier, Stephan Bickel, Pierre Megevand, David M. Groppe, Charles E. Schroeder, Ashesh D. Mehta, Fred A. Lado
While there is a strong interest in meso-scale field potential recording using intracranial electroencephalography with penetrating depth electrodes (i.e. stereotactic EEG or S-EEG) in humans, the signal recorded in the white matter remains ignored. White matter is generally considered electrically neutral and often included in the reference montage. Moreover, re-referencing electrophysiological data is a critical preprocessing choice that could drastically impact signal content and consequently the results of any given analysis. In the present stereotactic electroencephalography study, we first illustrate empirically the consequences of commonly used references (subdermal, white matter, global average, local montage) on inter-electrode signal correlation. Since most of these reference montages incorporate white matter signal, we next consider the difference between signals recorded in cortical gray matter and white matter. Our results reveal that electrode contacts located in the white matter record a mixture of activity, with part arising from the volume conduction (zero time delay) of activity from nearby gray matter. Furthermore, our analysis shows that white matter signal may be correlated with distant gray matter signal. While residual passive electrical spread from nearby matter may account for this relationship, our results suggest the possibility that this long distance correlation arises from the white matter fiber tracts themselves (i.e. activity from distant gray matter traveling along axonal fibers with time lag larger than zero); yet definitive conclusions about the origin of the white matter signal would require further experimental substantiation. By characterizing the properties of signals recorded in white matter and in gray matter, this study illustrates the importance of including anatomical prior knowledge when analyzing S-EEG data.



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Motivation, emotion regulation, and the latent structure of psychopathology: An integrative and convergent historical perspective

Publication date: Available online 3 January 2017
Source:International Journal of Psychophysiology
Author(s): Theodore P. Beauchaine, Aimee Zisner
Motivational models of psychopathology have long been advanced by psychophysiologists, and have provided key insights into neurobiological mechanisms of a wide range of psychiatric disorders. These accounts emphasize individual differences in activity and reactivity of bottom-up, subcortical neural systems of approach and avoidance in affecting behavior. Largely independent literatures emphasize the roles of top-down, cortical deficits in emotion regulation and executive function in conferring vulnerability to psychopathology. To date however, few models effectively integrate functions performed by bottom-up emotion generation system with those performed by top-down emotion regulation systems in accounting for alternative expressions of psychopathology. In this article, we present such a model, and describe how it accommodates the well replicated bifactor structure of psychopathology. We describe how excessive approach motivation maps directly into externalizing liability, how excessive passive avoidance motivation maps directly into internalizing liability, and how emotion dysregulation and executive function map onto general liability. This approach is consistent with the Research Domain Criteria initiative, which assumes that a limited number of brain systems interact to confer vulnerability to many if not most forms of psychopathology.



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IOP-details

Publication date: January 2017
Source:International Journal of Psychophysiology, Volume 111





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Editorial Board

Publication date: January 2017
Source:International Journal of Psychophysiology, Volume 111





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Instructions to Authors

Publication date: January 2017
Source:International Journal of Psychophysiology, Volume 111





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Reviewer Acknowledgment

Publication date: January 2017
Source:International Journal of Psychophysiology, Volume 111





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Best practices for repeated measures ANOVAs of ERP data: Reference, regional channels, and robust ANOVAs

Publication date: January 2017
Source:International Journal of Psychophysiology, Volume 111
Author(s): Joseph Dien
Analysis of variance (ANOVA) is a fundamental procedure for event-related potential (ERP) research and yet there is very little guidance for best practices. It is important for the field to develop evidence-based best practices: 1) to minimize the Type II error rate by maximizing statistical power, 2) to minimize the Type I error rate by reducing the latitude for varying procedures, and 3) to identify areas for further methodological improvements. While generic treatments of ANOVA methodology are available, ERP datasets have many unique characteristics that must be considered. In the present report, a novelty oddball dataset was utilized as a test case to determine whether three aspects of ANOVA procedures as applied to ERPs make a real-world difference: the effects of reference site, regional channels, and robust ANOVAs. Recommendations are provided for best practices in each of these areas.



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Psychometric considerations in the measurement of event-related brain potentials: Guidelines for measurement and reporting

Publication date: January 2017
Source:International Journal of Psychophysiology, Volume 111
Author(s): Peter E. Clayson, Gregory A. Miller
Failing to consider psychometric issues related to reliability and validity, differential deficits, and statistical power potentially undermines the conclusions of a study. In research using event-related brain potentials (ERPs), numerous contextual factors (population sampled, task, data recording, analysis pipeline, etc.) can impact the reliability of ERP scores. The present review considers the contextual factors that influence ERP score reliability and the downstream effects that reliability has on statistical analyses. Given the context-dependent nature of ERPs, it is recommended that ERP score reliability be formally assessed on a study-by-study basis. Recommended guidelines for ERP studies include 1) reporting the threshold of acceptable reliability and reliability estimates for observed scores, 2) specifying the approach used to estimate reliability, and 3) justifying how trial-count minima were chosen. A reliability threshold for internal consistency of at least 0.70 is recommended, and a threshold of 0.80 is preferred. The review also advocates the use of generalizability theory for estimating score dependability (the generalizability theory analog to reliability) as an improvement on classical test theory reliability estimates, suggesting that the latter is less well suited to ERP research. To facilitate the calculation and reporting of dependability estimates, an open-source Matlab program, the ERP Reliability Analysis Toolbox, is presented.



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The Circadian Oscillator of the Cerebral Cortex: Molecular, Biochemical and Behavioral Effects of Deleting the Arntl Clock Gene in Cortical Neurons

A molecular circadian oscillator resides in neurons of the cerebral cortex, but its role is unknown. Using the Cre-LoxP method, we have here abolished the core clock gene Arntl in those neurons. This mouse represents the first model carrying a deletion of a circadian clock component specifically in an extrahypothalamic cell type of the brain. Molecular analyses of clock gene expression in the cerebral cortex of the Arntl conditional knockout mouse revealed disrupted circadian expression profiles, whereas clock gene expression in the suprachiasmatic nucleus was still rhythmic, thus showing that Arntl is required for normal function of the cortical circadian oscillator. Daily rhythms in running activity and temperature were not influenced, whereas the resynchronization response to experimental jet-lag exhibited minor though significant differences between genotypes. The tail-suspension test revealed significantly prolonged immobility periods in the knockout mouse indicative of a depressive-like behavioral state. This phenotype was accompanied by reduced norepinephrine levels in the cerebral cortex. Our data show that Arntl is required for normal cortical clock function and further give reason to suspect that the circadian oscillator of the cerebral cortex is involved in regulating both circadian biology and mood-related behavior and biochemistry.

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Who's that Knocking at My Door? Neural Bases of Sound Source Identification

When hearing knocking on a door, a listener typically identifies both the action (forceful and repeated impacts) and the object (a thick wooden board) causing the sound. The current work studied the neural bases of sound source identification by switching listeners' attention toward these different aspects of a set of simple sounds during functional magnetic resonance imaging scanning: participants either discriminated the action or the material that caused the sounds, or they simply discriminated meaningless scrambled versions of them. Overall, discriminating action and material elicited neural activity in a left-lateralized frontoparietal network found in other studies of sound identification, wherein the inferior frontal sulcus and the ventral premotor cortex were under the control of selective attention and sensitive to task demand. More strikingly, discriminating materials elicited increased activity in cortical regions connecting auditory inputs to semantic, motor, and even visual representations, whereas discriminating actions did not increase activity in any regions. These results indicate that discriminating and identifying material requires deeper processing of the stimuli than discriminating actions. These results are consistent with previous studies suggesting that auditory perception is better suited to comprehend the actions than the objects producing sounds in the listeners' environment.

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Predictability of anthropomorphic measurements in implant selection for breast reconstruction: a retrospective cohort study

Abstract

Background

Preoperative implant planning for breast reconstruction is often at risk of being changed perioperatively. This study examined which factors are associated with a change of implant selection.

Methods

Women who had unilateral two-stage breast reconstruction between 2002 and 2007 were studied. Inclusion criteria were photographic evidence of preoperative skin markings indicating breast dimensions and a selected implant model. Multivariable logistic regression was used to identify variables associated with a changed selection.

Results

Among the 496 women studied, 308 preoperative implant choices (62.1%) were changed during surgery. A change in plan was significantly associated with symmetrization surgery involving contralateral reduction mammaplasty (OR = 1.92; 95% CI, 1.12 to 3.29) and contralateral mastopexy (OR = 2.26; 95% CI, 1.29 to 3.96), but not with BMI. The required implant width changed more than 0.5 cm in 70 cases (14.1%) while height changed more than 0.5 cm in 215 cases (43.2%). The likelihood of a change was high for large preoperative widths (OR = 9.66 for 15.5 cm) and small preoperative heights (OR = 2.97 for 10.5 cm). At a mean follow-up of 16.6 months, patient satisfaction was good or average in 92.1% of cases and 5.9% of implants had been replaced with another model, indicating that the perioperative implant selection was usually appropriate.

Conclusions

This study documents the frequency with which implant choices, despite accurate preoperative planning, are changed perioperatively as a result of relatively small differences in anthropomorphic measurements. Perioperative recalculation of breast dimensions may have an advantage in terms of patient reoperation rates. Changes in width were less frequent than changes in height and projection. Contralateral surgery, large width, and small height were the most influential factors.

Level of Evidence: Level IV, risk / prognostic study.

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Effects of Non-focused Microbubble-Enhanced and High-Intensity Focused Ultrasound on Hemostasis in a Rabbit Model of Liver Trauma

Publication date: Available online 3 January 2017
Source:Ultrasound in Medicine & Biology
Author(s): Da-Wei Zhao, Meng Tian, Jian-Zhong Zou, Yuan-Yi Zheng, Tao Li
Uncontrolled hemorrhage after trauma to the liver can lead to death. The present study compared the effects of non-focused microbubble-enhanced ultrasound and high-intensity focused ultrasound on hepatic hemostasis in the injured liver. Blood perfusion level, serum liver enzyme levels and the aspartate transaminase/alanine transaminase ratio differed between the two types of treatment (all p values < 0.05). Hepatic cells in the microbubble-enhanced ultrasound group exhibited edema and compressed the hepatic sinus and blood vessels in the portal area. Coagulation and necrosis, inflammatory cell infiltration, and fibrous tissue encapsulation were observed in the high-intensity focused ultrasound group at later stages. The groups also differed in degree of ultrastructural damage and recovery time. Thus, microbubble-enhanced ultrasound has less of an impact on blood reperfusion and surrounding normal tissue than high-intensity focused ultrasound and is a better choice for the treatment of liver trauma.



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Testicular Shear Wave Elastography in Normal and Infertile Men: A Prospective Study on 601 Patients

Publication date: Available online 3 January 2017
Source:Ultrasound in Medicine & Biology
Author(s): Laurence Rocher, Aline Criton, Jean-Luc Gennisson, Vincent Izard, Sophie Ferlicot, Mickael Tanter, Gerard Benoit, Marie France Bellin, Jean-Michel Correas
Our aim in the study described here was to prospectively establish the feasibility of using and reproducibility of testicular shear-wave elastography in the assessment of testicular stiffness in 62 normal patients and 539 infertile men with obstructive azoospermia (OA), non-Klinefelter syndrome non-obstructive azoospermia (non-KS NOA), Klinefelter syndrome NOA (KS NOA), oligoasthenoteratozoospermia (OAT) or a left varicocele. The feasibility rate was 96.9%, with an intra-class correlation coefficient of 0.85 (95% confidence interval: 0.83–0.88). Median stiffness (interquartile range) values were 2.4 kPa (2.0, 2.9), 2.1 kPa (1.8, 2.5), 2.4 kPa (2.0, 2.7), 2.0 kPa (1.7, 2.4), 2.6 kPa (2, 3.2) and 2.2 kPa (1.8, 2.6) for men with a normal testis (n = 108), OAT (n = 689), OA (n = 119), non-KS NOA (n = 183), KS NOA (n = 70) and varicocele (n = 132), respectively. Testicular shear wave elastography is a feasible and reproducible technique. A significant positive association was found between stiffness and testis volume (p = 0.001). Testicular stiffness was higher in OA than in non-KS NOA populations (p = 1.e−10) and in KS NOA than in NOA populations (p = 2.0e−8), but the substantial number of overlapping values limited the clinical impact.



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The antioxidant role of agomelatine and gallic acid on oxidative stress in STZ induced type I diabetic rat testes

Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Gurkan Yigitturk, Ahmet Cagdas Acara, Oytun Erbas, Fatih Oltulu, Nefise Ulku Karabay Yavasoglu, Aysegul Uysal, Altug Yavasoglu
Diabetes is a multisystem disorder and its effects are observed on the reproductive system. One of the main causes of testicular tissue damage is diabetes-induced overproduction of reactive oxygen species and glycated end products. The main objectives of this study were to investigate the possible effects of agomelatine (AG) and gallic acid (GA) in suppressing oxidative stress in Type I diabetes induced testicular damage. A total of 28 adult male rats were included in the study. Diabetes was induced by intraperitoneal injection of streptozocin (STZ, 55mg/kg) to 21 rats, which were then randomly assigned to 3 groups; 1mL saline solution was given to the diabetes+saline group by oral gavage, 20mg/kg/day oral AG was given to the diabetes+AG group, and 20mg/kg/day oral GA was given to the diabetes+GA group for 4 weeks. Tumor necrosis factor α (TNFα), nitric oxide synthase 2 (NOS2), fibronectin and vascular endothelial growth factor (VEGF) were used for the investigation of inflammation, fibrosis and vascular structures. The terminal-deoxynucleoitidyl-transferase mediated nick end-labeling assay (TUNEL) was used to detect apoptosis. Testicular tissue total antioxidant capacity values were tested by biochemical analysis. AG treatment showed an improvement on biochemical parameters and histopathological appearance on the rat testes. GA showed dose-related regenerative effects on biochemical parameters. Histologically, a minimal healing effect was determined on the testes damage. In conclusion, it was observed that AG is a potentially beneficial agent for reducing testicular damage by decreasing oxidative stress level. However, GA was seen to have a poor therapeutic effect.



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Synthesis, properties and biomedical applications of carbon-based quantum dots: An updated review

Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Pooria Namdari, Babak Negahdari, Ali Eatemadi
Carbon-based quantum dots (CQDs) are a newly developed class of carbon nano-materials that have attracted much interest and attention as promising competitors to already available semiconductor quantum dots owing to their un-comparable and unique properties. In addition, controllability of CQDs unique physiochemical properties is as a result of their surface passivation and functionalization. This is an update article (between 2013 and 2016) on the recent progress, characteristics and synthesis methods of CQDs and different advantages in varieties of applications.



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Potent antihyperglycemic and hypoglycemic effect of Tamarix articulata Vahl. in normal and streptozotocin-induced diabetic rats

Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Morad Hebi, Omra Farid, Mohammed Ajebli, Mohamed Eddouks
The purpose of this study was to investigate the effect of a single dose and daily oral administration for seven days of the aerial part aqueous extract (A.P.A.E) of Tamarix articulata Vahl. (T. articulata) (5mg/kg) on blood glucose levels in both normal and streptozotocin-induced diabetic rats (STZ). Single oral administration of T. articulata A.P.A.E reduced blood glucose levels 6h after administration in normal rats (p<0.0001) and STZ diabetic rats (p<0.001). Furthermore, blood glucose levels were decreased in both normal (p<0.05) and STZ diabetic rats (p<0.0001) after seven days of treatment. Moreover, no significant changes in body weight in normal and STZ rats were shown. According to the oral glucose tolerance test, the aqueous extract of T. articulata (5mg/kg) was shown to prevent significantly the increase on blood glucose levels in both normal and diabetic treated rats 30min, 60min and 120min after glucose administration when compared to the control group. Additionally, histopathological analysis revealed the beneficial effect of T. articulata on pancreas and liver. Finally, the antioxydant activity of the aqueous extract of Tamarix articulata was evaluated by the method of trapping of free radical 2,2-diphenyl-1 picrylhydrazyl (DPPH). Tamarix articulata revealed inhibitory concentrations of 50% of free radicals (IC50) of 203.15μg/ml. In contrast, the synthetic antioxidant butylhydroxytoluene (BHT) has showed an IC50 equal to 13.71μg/ml. In conclusion, this study demonstrates antihyperglycemic, hypoglycemic and antioxidant effects of T. articulata in severe diabetic state thus warrants further investigation on its major compounds as well as mechanistic studies.



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Berberine ameliorates intrahippocampal kainate-induced status epilepticus and consequent epileptogenic process in the rat: Underlying mechanisms

Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Reza Sedaghat, Yosra Taab, Zahra Kiasalari, Siamak Afshin-Majd, Tourandokht Baluchnejadmojarad, Mehrdad Roghani
Status epilepticus (SE) is a life-threatening neurologic condition, instigating epileptogenesis to transform normal brain to an epileptic condition. SE is followed by spontaneous recurrent seizures (SRS) and final development of temporal lobe epilepsy (TLE) that is resistant to treatment. Neuroprotective strategies are increasingly put forward as a promising therapy to prevent and/or manage epileptic conditions. In this study, we investigated whether berberis alkaloid, i.e. berberine (BBR), could ameliorate intrahippocampal kainate-induced SE and its consequent epileptogenic process and to explore some underlying mechanisms. BBR was daily administered at doses of 25 or 50mg/kg. Results showed that BBR treatment of kainate-microinjected rats at a dose of 50mg/kg lowered the incidence of SE and SRS. It also significantly restored hippocampal level of reactive oxygen species (ROS), glutathione (GSH), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), activity of catalase and caspase 3, nuclear factor-<kappa>B (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), neural cell adhesion molecule (NCAM), glial fibrillary acidic protein (GFAP), cathepsin D, and heme oxygenase 1 (HO-1). Additionally, BBR protected against hippocampal CA3 neuronal loss and prevented development of aberrant mossy fiber sprouting (MFS) as an essential element of chronic epileptogenic circuit. These data suggest that BBR could mitigate SE and SRS in intrahippocampal kainate model of epilepsy and exert neuroprotective effect and its influence is mainly mediated via suppression of oxidative stress, neuroinflammation, and possibly apoptosis.



http://ift.tt/2hPsX3u

Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney

Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Saeed Samarghandian, Mohsen Azimi-Nezhad, Tahereh Farkhondeh, Fariborz Samini
Restraint stress has been indicated to induce oxidative damage in tissues. Several investigations have reported that curcumin (CUR) may have a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CUR on restraint stress induced oxidative stress damage in the brain, liver and kidneys. For chronic restraint stress, rats were kept in the restrainers for 1h every day, for 21 consecutive days. The animals received systemic administrations of CUR daily for 21days. In order to evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), as well as antioxidant enzyme activities superoxide dismutase (SOD) glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were measured in the brain, liver and kidney of rats after the end of restraint stress. The restraint stress significantly increased MDA level, but decreased the level of GSH and activists of SOD, GPx, GR, and CAT the brain, liver and kidney of rats in comparison to the normal rats (P<0.001). Intraperitoneal administration of CUR significantly attenuated oxidative stress and lipid peroxidation, prevented apoptosis, and increased antioxidant defense mechanism activity in the tissues versus the control group (P<0.05). This study shows that CUR can prevent restraint stress–induced oxidative damage in the brain, liver and kidney of rats and propose that CUR may be useful agents against oxidative stress in the tissues.



http://ift.tt/2iNsSdr

Mechanism of Synergistic DNA Damage induced by the Hydroquinone Metabolite of Brominated Phenolic Environmental Pollutants and Cu(II): Formation of DNA-Cu Complex and Site-specific Production of Hydroxyl Radicals

Publication date: Available online 3 January 2017
Source:Free Radical Biology and Medicine
Author(s): Bo Shao, Li Mao, Na Qu, Ya-Fen Wang, Hui-Ying Gao, Feng Li, Li Qin, Jie Shao, Chun-Hua Huang, Dan Xu, Lin-Na Xie, Chen Shen, Xiang Zhou, Ben-Zhan Zhu
2,6-Dibromohydroquinone (2,6-DBrHQ) has been identified as an reactive metabolite of many brominated phenolic environmental pollutants such as tetrabromobisphenol-A (TBBPA), bromoxynil and 2,4,6-tribromophenol, and was also found as one of disinfection byproducts in drinking water. In this study, we found that the combination of 2,6-DBrHQ and Cu(II) together could induce synergistic DNA damage as measured by double strand breakage in plasmid DNA and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, while either of them alone has no effect. 2,6-DBrHQ/Cu(II)-induced DNA damage could be inhibited by the Cu(I)-specific chelating agent bathocuproine disulfonate and catalase, but not by superoxide dismutase, nor by the typical hydroxyl radical (•OH) scavengers such as DMSO and mannitol. Interestingly, we found that Cu(II)/Cu(I) could be combined with DNA to form DNA-Cu(II)/Cu(I) complex by complementary application of low temperature direct ESR, circular dichroism, cyclic voltammetry and oxygen consumption methods; and the highly reactive •OH were produced synergistically by DNA-bound-Cu(I) with H2O2 produced by the redox reactions between 2,6-DBrHQ and Cu(II), which then immediately attack DNA in a site-specific manner as demonstrated by both fluorescent method and by ESR spin-trapping studies. Further DNA sequencing investigations provided more direct evidence that 2,6-DBrHQ/Cu(II) caused preferential cleavage at guanine, thymine and cytosine residues. Based on these data, we proposed that the synergistic DNA damage induced by 2,6-DBrHQ/Cu(II) might be due to the synergistic and site-specific production of •OH near the binding site of copper and DNA. Our findings may have broad biological and environmental implications for future research on the carcinogenic polyhalogenated phenolic compounds.

Graphical abstract

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Redox Signaling In The Gastrointestinal Tract

Publication date: Available online 3 January 2017
Source:Free Radical Biology and Medicine
Author(s): Salvador Pérez, Raquel Taléns-Visconti, Sergio Rius-Pérez, Isabela Finamor, Juan Sastre
Redox signaling regulates physiological self-renewal, proliferation, migration and differentiation in gastrointestinal epithelium by modulating Wnt/β-catenin and Notch signaling pathways mainly through NADPH oxidases (NOXs). In the intestine, intracellular and extracellular thiol redox status modulates the proliferative potential of epithelial cells. Furthermore, commensal bacteria contribute to intestine epithelial homeostasis through NOX1- and dual oxidase 2-derived reactive oxygen species (ROS). The loss of redox homeostasis is involved in the pathogenesis and development of a wide diversity of gastrointestinal disorders, such as Barrett's esophagus, esophageal adenocarcinoma, peptic ulcer, gastric cancer, ischemic intestinal injury, celiac disease, inflammatory bowel disease and colorectal cancer. The overproduction of superoxide anion together with inactivation of superoxide dismutase are involved in the pathogenesis of Barrett's esophagus and its transformation to adenocarcinoma. In Helicobacter pylori-induced peptic ulcer, oxidative stress derived from the leukocyte infiltrate and NOX1 aggravates mucosal damage, especially in HspB+ strains that downregulate Nrf2. In celiac disease, oxidative stress mediates most of the cytotoxic effects induced by gluten peptides and increases transglutaminase levels, whereas nitrosative stress contributes to the impairment of tight junctions. Progression of inflammatory bowel disease relies on the balance between pro-inflammatory redox-sensitive pathways, such as NLRP3 inflammasome and NF-κB, and the adaptive up-regulation of Mn superoxide dismutase and glutathione peroxidase 2. In colorectal cancer, redox signaling exhibits two Janus faces: On the one hand, NOX1 up-regulation and derived hydrogen peroxide enhance Wnt/β-catenin and Notch proliferating pathways; on the other hand, ROS may disrupt tumor progression through different pro-apoptotic mechanisms. In conclusion, redox signaling plays a critical role in the physiology and pathophysiology of gastrointestinal tract.

Graphical abstract

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Aspirin plus sorafenib potentiates cisplatin cytotoxicity in resistant head and neck cancer cells through xCT inhibition

Publication date: Available online 3 January 2017
Source:Free Radical Biology and Medicine
Author(s): Jong-Lyel Roh, Eun Hye Kim, Hyejin Jang, Daiha Shin
The nonsteroidal anti-inflammatory drug aspirin and the multikinase inhibitor sorafenib have both shown experimental and clinical anticancer activities. The present study investigated whether aspirin and sorafenib synergize to potentiate cisplatin treatment in resistant head and neck cancer (HNC) cells. The effects of aspirin, sorafenib and cisplatin, and combinations thereof were assessed by measuring cell viability, death, glutathione (GSH) and reactive oxygen species (ROS) levels, protein and mRNA expression, genetic inhibition and overexpression of cystine–glutamate antiporter (xCT) and tumor xenograft mouse models. Even at low concentrations, aspirin plus sorafenib synergized to induce cell death of cisplatin-resistant HNC cells. The combination of aspirin and sorafenib induced xCT inhibition, GSH depletion, and ROS accumulation in cancer cells. Genetic and pharmacological inhibition of xCT potentiated the cytotoxic effects of aspirin plus sorafenib; this effect was diminished by xCT overexpression. Low-dose aspirin plus sorafenib enhanced the cytotoxicity of cisplatin in resistant HNC cells through xCT inhibition and oxidant and DNA damage. The in vivo effects of aspirin plus sorafenib on cisplatin therapy were also confirmed in resistant HNC xenograft models, in terms of growth inhibition, GSH depletion, and increased γH2AX formation and apoptosis in tumors. Aspirin and sorafenib synergize to potentiate the cytotoxicity of cisplatin in resistant HNC cells. This therapeutic strategy may help to eliminate resistant HNC.

Graphical abstract

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Oxysterols and 4-hydroxy-2-nonenal contribute to atherosclerotic plaque destabilization

Publication date: Available online 3 January 2017
Source:Free Radical Biology and Medicine
Author(s): Simona Gargiulo, Gabriella Testa, Paola Gamba, Erica Staurenghi, Giuseppe Poli, Gabriella Leonarduzzi
A growing bulk of evidence suggests that cholesterol oxidation products, known as oxysterols, and 4-hydroxy-2-nonenal (HNE), the major proatherogenic components of oxidized low density lipoproteins (oxLDLs), significantly contribute to atherosclerotic plaque progression and destabilization, with eventual plaque rupture. These oxidized lipids are involved in various key steps of this complex process, mainly thanks to their ability to induce inflammation, oxidative stress, and apoptosis. This review summarizes the current knowledge of the effects induced by these compounds on vascular cells, after their accumulation in the arterial wall and in the atherosclerotic plaque.



http://ift.tt/2iBzuvK

MANAGEMENT OF ENDOCRINE DISEASE: Regenerative therapies in autoimmune Addisons disease

The treatment for autoimmune Addison's disease (AAD) has remained virtually unchanged in the last 60 years. Most patients have symptoms that are relatively well controlled with exogenous steroid replacement, but there may be persistent symptoms, recurrent adrenal crisis and poor quality of life, despite good compliance with optimal current treatments. Treatment with conventional exogenous steroid therapy is also associated with premature mortality, increased cardiovascular risk and complications related to excessive steroid replacement. Hence, novel therapeutic approaches have emerged in the last decade attempting to improve the long-term outcome and quality of life of patients with AAD. This review discusses the recent developments in treatment innovations for AAD, including the novel exogenous steroid formulations with the intention of mimicking the physiological biorhythm of cortisol secretion. Our group has also carried out a few studies attempting to restore endogenous glucocorticoid production via immunomodulatory and regenerative medicine approaches. The recent advances in the understanding of adrenocortical stem cell biology, and adrenal plasticity will also be discussed to help comprehend the science behind the therapeutic approaches adopted.

http://ift.tt/2iGn7kB

Association of adrenal insufficiency with insulin-dependent diabetes mellitus in a patient with inactivating mutations in nicotinamide nucleotide transhydrogenase: a phenocopy of the animal model

http://ift.tt/2j2Dg0i

MANAGEMENT OF ENDOCRINE DISEASE: Growth and growth hormone therapy in short children born preterm

Approximately 15 million babies are born preterm across the world every year, with less than 37 completed weeks of gestation. Survival rates increased during the last decades with the improvement of neonatal care. With premature birth, babies are deprived of the intense intrauterine growth phase, and postnatal growth failure might occur. Some children born prematurely will remain short at later ages and adult life. The risk of short stature increases if the child is also born small for gestational age. In this review, the effects of being born preterm on childhood growth and adult height and the hormonal abnormalities possibly associated with growth restriction are discussed, followed by a review of current information on growth hormone treatment for those who remain with short stature during infancy and childhood.

http://ift.tt/2iGiAi8

MECHANISMS IN ENDOCRINOLOGY: Diabetes mellitus, a state of low bone turnover - a systematic review and meta-analysis

Objective

To investigate the differences in bone turnover between diabetic patients and controls.

Design

A systematic review and meta-analysis.

Methods

A literature search was conducted using the databases Medline at PubMed and EMBASE. The free text search terms 'diabetes mellitus' and 'bone turnover', 'sclerostin', 'RANKL', 'osteoprotegerin', 'tartrate-resistant acid' and 'TRAP' were used. Studies were eligible if they investigated bone turnover markers in patients with diabetes compared with controls. Data were extracted by two reviewers.

Results

A total of 2881 papers were identified of which 66 studies were included. Serum levels of the bone resorption marker C-terminal cross-linked telopeptide (–0.10 ng/mL (–0.12, –0.08)) and the bone formation markers osteocalcin (–2.51 ng/mL (–3.01, –2.01)) and procollagen type 1 amino terminal propeptide (–10.80 ng/mL (–12.83, –8.77)) were all lower in patients with diabetes compared with controls. Furthermore, s-tartrate-resistant acid phosphatase was decreased in patients with type 2 diabetes (–0.31 U/L (–0.56, –0.05)) compared with controls. S-sclerostin was significantly higher in patients with type 2 diabetes (14.92 pmol/L (3.12, 26.72)) and patients with type 1 diabetes (3.24 pmol/L (1.52, 4.96)) compared with controls. Also, s-osteoprotegerin was increased among patients with diabetes compared with controls (2.67 pmol/L (0.21, 5.14)).

Conclusions

Markers of both bone formation and bone resorption are decreased in patients with diabetes. This suggests that diabetes mellitus is a state of low bone turnover, which in turn may lead to more fragile bone. Altered levels of sclerostin and osteoprotegerin may be responsible for this.

http://ift.tt/2j2DDrv

Use of nanoparticles with Escherichia coli receptors for prophylaxis of recurrent urinary tract infections in children

Publication date: Available online 3 January 2017
Source:Medical Hypotheses
Author(s): Ilke Beyitler, Salih Kavukcu




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Plant-based Diets Relatively Low in Bioavailable Phosphate and Calcium May Aid Prevention and Control of Prostate Cancer by Lessening Production of Fibroblast Growth Factor 23

Publication date: Available online 3 January 2017
Source:Medical Hypotheses
Author(s): Mark F. McCarty
Fibroblast growth factor 23 (FGF23), a hormonal regulator of phosphate and vitamin D metabolism produced primarily in bone by osteocytes and mature osteoblasts, is now known to have growth factor activity for many prostate cancers. In some of these cancers, autocrine production of FGF23 drives their proliferation. FGF23 synthesized within bone likely promotes the expansion of prostate cancer bone metastases. Hence, dietary or lifestyle factors which boost bone's production of FGF23 may encourage the induction and spread of prostate cancer. High dietary intakes of bioavailable phosphorus and of calcium have been found to boost FGF23 levels, and this accords well with prospective epidemiology pointing to high intakes of both phosphate and calcium as risk factors for aggressive prostate cancer. Hence, prospective studies correlating baseline FGF23 levels with subsequent risk for prostate cancer, or advanced prostate cancer, are needed. Natural plant-based diets, though not inherently low in calcium or phosphorus, provide forms of these that are less bioavailable than those in animal products, and hence may be expected to down-regulate bone's production of FGF23. This may play a role in the lower risk for clinical prostate cancer observed in vegans and quasi-vegan cultures. Other factors, such as decreased IGF-I levels and mTORC1 activity, may also play a role in this regard.



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Responses of CO2 emission and pore water DOC concentration to soil warming and water table drawdown in Zoige Peatlands

Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): Gang Yang, Mei Wang, Huai Chen, Liangfeng Liu, Ning Wu, Dan Zhu, Jianqing Tian, Changhui Peng, Qiuan Zhu, Yixin He
Peatlands in Zoige Plateau contains more than half of peatland carbon stock in China. This part of carbon is losing with climate change through dissolved organic carbon (DOC) export and carbon dioxide (CO2) emissions, both of which are vulnerable to the environmental changes, especially on the Zoige Plateau with a pace of twice the observed rate of global climate warming. This research aimed to understand how climate change including soil warming, rainfall reduction and water table change affect CO2 emissions and whether the trends of changes in CO2 emission are consistent with those of pore water DOC concentration. A mesocosm experiment was designed to investigate the CO2 emission and pore water DOC during the growing seasons of 2009–2010 under scenarios of passive soil warming, 20% rainfall reduction and changes to the water table levels. The results showed a positive relationship between CO2 emission and DOC concentration. For single factor effect, we found no significant relationship between water table and CO2 emission or DOC concentration. However, temperature at 5 cm depth was found to have positive linear relationship with CO2 emission and DOC concentration. The combined effect of soil warming and rainfall reduction increased CO2 emission by 96.8%. It suggested that the drying and warming could stimulate potential emission of CO2. Extending this result to the entire peatland area in Zoige Plateau translates into 0.45 Tg CO2 emission per year over a growing season. These results suggested that the dryer and warmer Zoige Plateau will increase CO2 emission. We also found the contribution rate of DOC concentration to CO2 emission was increased by 12.1% in the surface layer and decreased by 13.8% in the subsurface layer with combined treatment of soil warming and rainfall reduction, which indicated that the warmer and dryer environmental conditions stimulate surface peat decomposition process.

Graphical abstract

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Effects of low-level laser irradiation on human blood lymphocytes in vitro

Abstract

Low-level laser irradiation (LLLI) has various effects on cultured human lymphocytes in vitro, but little is known about such effects in whole blood. This study investigated whether LLLI affected lymphocyte count in human whole blood in vitro. A total number of 130 blood samples were collected from apparently healthy adult patients through venipuncture into tubes containing EDTA. Each sample was divided into two equal aliquots to be used as a non-irradiated control sample and an irradiated sample. The irradiated aliquot was subjected to laser wavelengths of 405, 589, and 780 nm with different fluences of 36, 54, 72, and 90 J/cm², at a fixed irradiance of 30 mW/cm². A paired student t test was used to compare between non-irradiated and irradiated samples. The lymphocyte counts were measured using a computerized hematology analyzer and showed a significant (P < 0.02) maximum increase (1.6%) at a fluence of 72 J/cm² when compared with non-irradiated samples. This increase in lymphocyte count upon irradiation was confirmed by flow cytometry. At a wavelength of 589 nm and fluence of 72 J/cm², irradiation of whole blood samples showed a significant increase in CD45 lymphocytes and natural killer (NK) (CD16, CD56) cells, but no significant changes in CD3 T lymphocytes, T-suppressor (CD3, CD8) cells, T-helper (CD3, CD4) cells, and CD19 B lymphocytes when compared with their non-irradiated counterparts. Our results clearly demonstrate that NK cell count is altered by irradiation, which ultimately affects the whole lymphocyte count significantly.

http://ift.tt/2j4nh60

Short-Chain Fatty Acids Inhibit Oxidative Stress and Inflammation in Mesangial Cells Induced by High Glucose and Lipopolysaccharide

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-121493

Recently, an connection between Short-chain fatty acids (SCFAs) produced by intestinal microbiota and kidney has been revealed. The aim of this study was to explore whether SCFAs or their specific G protein-coupled receptors 43 (GPR43) agonist inhibit oxidative stress and inflammatory response in glomerular mesangial cells (GMCs) induced by high glucose and lipopolysaccharide (LPS). Our research showed that treatment with SCFAs, especially acetate and butyrate, or GPR43 agonist significantly inhibited GMCs proliferation induced by high glucose and LPS, and then reversed the production of reactive oxygen species (ROS) and malondialdehyde (MDA) but increased levels of antioxidant enzyme superoxide dismutase (SOD). Furthermore, SCFAs or GPR43 agonist obviously increased the protein expression of GPR43 induced by high glucose and LPS, but diminished the expression of adhesion molecule intercellular adhesion molecule-1 (ICAM-1), and then decreased the proinflammatory cytokine monocyte chemoattractant protein (MCP-1) and interleukin-1β (IL-1β) release from GMCs stimulated by the high glucose and LPS. These combined results support the hypothesis that SCFAs or GPR43 agonist can inhibit oxidative stress and inflammation of GMCs induced by high glucose and LPS, suggesting that SCFAs induced signaling pathway may act as new therapeutic targets of diabetic nephropathy (DN).
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Role of the polycarboxylic compounds in the response of Silene vulgaris to chromium

Abstract

This work aims to investigate the nature and the specific mechanisms by which polycarboxylic compounds participate in the tolerance of Silene vulgaris to Cr with special attention given to the rhizosphere system. This knowledge is important to use this species in the implementation of phytoremediation technologies in Cr-polluted soils. According to the results, chromium is chelated and mobilized by the citric and malic acids in plant tissues, while oxalic acid might participate in the reduction and chelation of Cr in the rhizosphere. At the applied doses, the response of both exudation rate and root exudate composition (total polyphenols and quercitin) seems to involve a rearrangement in the lignification of the plant cell wall to immobilize Cr. Quercetin-3-dirhamnosyl-galactoside and apiin (apigenin-7-O-apiosyl-glucoside) have been identified as the major polyphenols in the root exudates of S. vulgaris. The increments found in the apiin concentration in root exudates seem to be related to the protection against Cr toxicity by chelation of Cr or by free radical scavenging. Though earlier response is detected in plant tissues, results from this work together with previous studies in S. vulgaris indicate that exudation might be a regulated mechanism of protection under Cr exposition in S. vulgaris that may involve mainly Cr reduction and chelation.

http://ift.tt/2j6A87z

Analysis of the impact path on factors of China’s energy-related CO 2 emissions: a path analysis with latent variables

Abstract

Identifying the impact path on factors of CO₂ emissions is crucial for the government to take effective measures to reduce carbon emissions. The most existing research focuses on the total influence of factors on CO₂ emissions without differentiating between the direct and indirect influence. Moreover, scholars have addressed the relationships among energy consumption, economic growth, and CO₂ emissions rather than estimating all the causal relationships simultaneously. To fill this research gaps and explore overall driving factors' influence mechanism on CO₂ emissions, this paper utilizes a path analysis model with latent variables (PA-LV) to estimate the direct and indirect effect of factors on China's energy-related carbon emissions and to investigate the causal relationships among variables. Three key findings emanate from the analysis: (1) The change in the economic growth pattern inhibits the growth rate of CO₂ emissions by reducing the energy intensity; (2) adjustment of industrial structure contributes to energy conservation and CO₂ emission reduction by raising the proportion of the tertiary industry; and (3) the growth of CO₂ emissions impacts energy consumption and energy intensity negatively, which results in a negative impact indirectly on itself. To further control CO₂ emissions, the Chinese government should (1) adjust the industrial structure and actively develop its tertiary industry to improve energy efficiency and develop low-carbon economy, (2) optimize population shifts to avoid excessive population growth and reduce energy consumption, and (3) promote urbanization steadily to avoid high energy consumption and low energy efficiency.

http://ift.tt/2i82JoO

Occurrence, spatial distribution, and ecological risks of typical hydroxylated polybrominated diphenyl ethers in surface sediments from a large freshwater lake of China

Abstract

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been frequently observed in marine aquatic environments; however, little information is available on the occurrence of these compounds in freshwater aquatic environments, including freshwater lakes. In this study, we investigated the occurrence and spatial distribution of typical OH-PBDEs, including 2′-OH-BDE-68, 3-OH-BDE-47, 5-OH-BDE-47, and 6-OH-BDE-47 in surface sediments of Taihu Lake. 3-OH-BDE-47 was the predominant congener, followed by 5-OH-BDE-47, 2′-OH-BDE-68, and 6-OH-BDE-47. Distributions of these compounds are drastically different between sampling site which may be a result of differences in nearby point sources, such as the discharge of industrial wastewater and e-waste leachate. The positive correlation between ∑OH-PBDEs and total organic carbon (TOC) was moderate (r = 0.485, p < 0.05), and site S3 and S15 were excluded due to point source pollution, suggesting that OH-PBDEs concentrations were controlled by sediment TOC content, as well as other factors. The pairwise correlations between the concentrations of these compounds suggest that these compounds may have similar input sources and environmental behavior. The target compounds in the sediments of Lake Taihu pose low risks to aquatic organisms. Results show that OH-PBDEs in Lake Taihu are largely dependent on pollution sources. Because of bioaccumulation and subsequent harmful effects on aquatic organisms, the concentrations of OH-PBDEs in freshwater ecosystems are of environmental concern.

http://ift.tt/2j6Aifi

Effects of Long-Term Vitamin D Supplementation on Regression and Metabolic Status of Cervical Intraepithelial Neoplasia: a Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

We are not aware of any study examining the effects of long term vitamin D administration on regression and metabolic status of patients with cervical intraepithelial neoplasia grade 1 (CIN1). This study was performed to evaluate the effects of long-term vitamin D administration on regression and metabolic status of patients with CIN1. This randomized, double-blind, placebo-controlled trial was performed among 58 women diagnosed with CIN1. CIN1 diagnosis was performed based on specific diagnostic procedures of biopsy, pathological diagnosis, and colposcopy. Patients were randomly allocated into two groups to take 50,000 IU vitamin D3 supplements (n = 29) or placebo (n = 29) every 2 weeks for 6 months. Fasting blood samples were taken at the beginning of the study and end-of-trial to measure related markers. After 6 months of vitamin D administration, greater percentage of women in the vitamin D group had regressed CIN1 (84.6 vs. 53.8%, P = 0.01) than those in the placebo group. Long-term vitamin D supplementation increased serum-25(OH) vitamin D levels in the intervention group compared to the placebo group (+12.3 ± 11.4 vs. -0.1 ± 3.7 ng/mL, P < 0.001). In addition, vitamin D intake led to significant decreases in serum insulin levels (−5.3 ± 7.3 vs. +2.4 ± 5.9 μIU/mL, P < 0.001), homeostasis model of assessment-insulin resistance (−1.2 ± 1.6 vs. +0.5 ± 1.2, P < 0.001), homeostatic model assessment-Beta cell function (P = 0.005) and a significant elevation in quantitative insulin sensitivity check index (+0.03 ± 0.04 vs. -0.007 ± 0.02, P < 0.001) compared with the placebo group. Additionally, significant increases in plasma nitric oxide (NO) (+15.5 ± 10.3 vs. +4.0 ± 13.4 μmol/L, P = 0.001), total antioxidant capacity (TAC) (P = 0.04), total glutathione (GSH) (+11.8 ± 153.5 vs. -294.2 ± 595.1 μmol/L, P = 0.01) and a significant reduction in plasma malondialdehyde (MDA) levels (−0.8 ± 1.0 vs. -0.03 ± 1.4 μmol/L, P = 0.03) were observed following the administration of vitamin D supplements compared with the placebo group. In conclusion, vitamin D3 administration for 6 months among women with CIN1 resulted in its regression and had beneficial effects on markers of insulin metabolism, plasma NO, TAC, GSH and MDA levels.

Clinical trial registration number www.irct.ir: IRCT201412065623N30.

http://ift.tt/2iwZcUk

Thyroid Hormone Controls Breast Cancer Cell Movement via Integrin αV/β3/SRC/FAK/PI3-Kinases

Abstract

Thyroid hormones (TH) play a fundamental role in diverse processes, including cellular movement. Cell migration requires the integration of events that induce changes in cell structure towards the direction of migration. These actions are driven by actin remodeling and stabilized by the development of adhesion sites to extracellular matrix via transmembrane receptors linked to the actin cytoskeleton. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that promotes cell migration and invasion through the control of focal adhesion turnover. In this work, we demonstrate that the thyroid hormone triiodothyronine (T3) regulates actin remodeling and cell movement in breast cancer T-47D cells through the recruitment of FAK. T3 controls FAK phosphorylation and translocation at sites where focal adhesion complexes are assembled. This process is triggered via rapid signaling to integrin αV/β3, Src, phosphatidylinositol 3-OH kinase (PI3K), and FAK. In addition, we established a cellular model with different concentration of T3 levels: normal, absence, and excess in T-47D breast cancer cells. We found that the expression of Src, FAK, and PI3K remained at normal levels in the excess of T3 model, while it was significantly reduced in the absence model. In conclusion, these results suggest a novel role for T3 as an important modulator of cell migration, providing a starting point for the development of new therapeutic strategies for breast cancer treatment.

http://ift.tt/2hNvdmZ

Micro-RNA-204 Participates in TMPRSS2/ERG Regulation and Androgen Receptor Reprogramming in Prostate Cancer

Abstract

Cancer progression is driven by genome instability incurred rearrangements such as transmembrane protease, serine 2 (TMPRSS2)/v-ets erythroblastosis virus E26 oncogene (ERG) that could possibly turn some of the tumor suppressor micro-RNAs into pro-oncogenic ones. Previously, we found dualistic miR-204 effects, acting either as a tumor suppressor or as an oncomiR in ERG fusion-dependent manner. Here, we provided further evidence for an important role of miR-204 for TMPRSS2/ERG and androgen receptor (AR) signaling modulation and fine tuning that prevents TMPRSS2/ERG overexpression in prostate cancer. Based on proximity-based ligation assay, we designed a novel method for detection of TMPRSS2/ERG protein products. We found that miR-204 is TMPRSS2/ERG oncofusion negative regulator, and this was mediated by DNA methylation of TMPRSS2 promoter. Transcriptional factors runt-related transcription factor 2 (RUNX2) and ETS proto-oncogene 1 (ETS1) were positive regulators of TMPRSS2/ERG expression and promoter hypo-methylation. Clustering of patients' sera for fusion protein, transcript expression, and wild-type ERG transcript isoforms, demonstrated not all patients harboring fusion transcripts had fusion protein products, and only few fusion positive ones exhibited increased wild-type ERG transcripts. miR-204 upregulated AR through direct promoter hypo-methylation, potentiated by the presence of ERG fusion and RUNX2 and ETS1. Proteomics studies provided evidence that miR-204 has dualistic role in AR cancer-related reprogramming, promoting prostate cancer-related androgen-responsive genes and AR target genes, as well as AR co-regulatory molecules. miR-204 methylation regulation was supported by changes in molecules responsible for chromatin remodeling, DNA methylation, and its regulation. In summary, miR-204 is a mild regulator of the AR function during the phase of preserved AR sensitivity as the latter one is required for ERG-fusion translocation.

http://ift.tt/2ix5jaW

Image-based gradient non-linearity characterization to determine higher-order spherical harmonic coefficients for improved spatial position accuracy in magnetic resonance imaging

Publication date: May 2017
Source:Magnetic Resonance Imaging, Volume 38
Author(s): Paul T. Weavers, Shengzhen Tao, Joshua D. Trzasko, Yunhong Shu, Erik J. Tryggestad, Jeffrey L. Gunter, Kiaran P. McGee, Daniel V. Litwiller, Ken-Pin Hwang, Matt A. Bernstein
PurposeSpatial position accuracy in magnetic resonance imaging (MRI) is an important concern for a variety of applications, including radiation therapy planning, surgical planning, and longitudinal studies of morphologic changes to study neurodegenerative diseases. Spatial accuracy is strongly influenced by gradient linearity. This work presents a method for characterizing the gradient non-linearity fields on a per-system basis, and using this information to provide improved and higher-order (9th vs. 5th) spherical harmonic coefficients for better spatial accuracy in MRI.MethodsA large fiducial phantom containing 5229 water-filled spheres in a grid pattern is scanned with the MR system, and the positions all the fiducials are measured and compared to the corresponding ground truth fiducial positions as reported from a computed tomography (CT) scan of the object. Systematic errors from off-resonance (i.e., B0) effects are minimized with the use of increased receiver bandwidth (±125kHz) and two acquisitions with reversed readout gradient polarity. The spherical harmonic coefficients are estimated using an iterative process, and can be subsequently used to correct for gradient non-linearity. Test-retest stability was assessed with five repeated measurements on a single scanner, and cross-scanner variation on four different, identically-configured 3T wide-bore systems.ResultsA decrease in the root-mean-square error (RMSE) over a 50cm diameter spherical volume from 1.80mm to 0.77mm is reported here in the case of replacing the vendor's standard 5th order spherical harmonic coefficients with custom fitted 9th order coefficients, and from 1.5mm to 1mm by extending custom fitted 5th order correction to the 9th order. Minimum RMSE varied between scanners, but was stable with repeated measurements in the same scanner.ConclusionsThe results suggest that the proposed methods may be used on a per-system basis to more accurately calibrate MR gradient non-linearity coefficients when compared to vendor standard corrections.



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A simple analytic method for estimating T2 in the knee from DESS

Publication date: May 2017
Source:Magnetic Resonance Imaging, Volume 38
Author(s): B Sveinsson, AS Chaudhari, GE Gold, BA Hargreaves
PurposeTo introduce a simple analytical formula for estimating T2 from a single Double-Echo in Steady-State (DESS) scan.MethodsExtended Phase Graph (EPG) modeling was used to develop a straightforward linear approximation of the relationship between the two DESS signals, enabling accurate T2 estimation from one DESS scan. Simulations were performed to demonstrate cancellation of different echo pathways to validate this simple model. The resulting analytic formula was compared to previous methods for T2 estimation using DESS and fast spin-echo scans in agar phantoms and knee cartilage in three volunteers and three patients. The DESS approach allows 3D (256×256×44) T2-mapping with fat suppression in scan times of 3–4min.ResultsThe simulations demonstrated that the model approximates the true signal very well. If the T1 is within 20% of the assumed T1, the T2 estimation error was shown to be less than 5% for typical scans. The inherent residual error in the model was demonstrated to be small both due to signal decay and opposing signal contributions. The estimated T2 from the linear relationship agrees well with reference scans, both for the phantoms and in vivo. The method resulted in less underestimation of T2 than previous single-scan approaches, with processing times 60 times faster than using a numerical fit.ConclusionA simplified relationship between the two DESS signals allows for rapid 3D T2 quantification with DESS that is accurate, yet also simple. The simplicity of the method allows for immediate T2 estimation in cartilage during the MRI examination.



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Semi-quantitative analysis of salivary gland scintigraphy in Sjögren’s syndrome diagnosis: a first-line tool

Abstract

Objective

The aim of this study was the assessment of semi-quantified salivary gland dynamic scintigraphy (SGdS) parameters independently and in an integrated way in order to predict primary Sjögren's syndrome (pSS).

Materials and methods

Forty-six consecutive patients (41 females; age 61 ± 11 years) with sicca syndrome were studied by SGdS after injection of 200 MBq of pertechnetate. In sixteen patients, pSS was diagnosed, according to American-European Consensus Group criteria (AECGc).

Semi-quantitative parameters (uptake (UP) and excretion fraction (EF)) were obtained for each gland. ROC curves were used to determine the best cut-off value. The area under the curve (AUC) was used to estimate the accuracy of each semi-quantitative analysis.

To assess the correlation between scintigraphic results and disease severity, semi-quantitative parameters were plotted versus Sjögren's syndrome disease activity index (ESSDAI). A nomogram was built to perform an integrated evaluation of all the scintigraphic semi-quantitative data.

Results

Both UP and EF of salivary glands were significantly lower in pSS patients compared to those in non-pSS (p < 0.001). ROC curve showed significantly large AUC for both the parameters (p < 0.05).

Parotid UP and submandibular EF, assessed by univariated and multivariate logistic regression, showed a significant and independent correlation with pSS diagnosis (p value <0.05). No correlation was found between SGdS semi-quantitative parameters and ESSDAI. The proposed nomogram accuracy was 87%.

Conclusion

SGdS is an accurate and reproducible tool for the diagnosis of pSS. ESSDAI was not shown to be correlated with SGdS data.

Clinical relevance

SGdS should be the first-line imaging technique in patients with suspected pSS.

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Head-to-head comparison between 18 F-FDOPA PET/CT and MR/CT angiography in clinically recurrent head and neck paragangliomas

Abstract

Purpose

Head and neck paragangliomas (HNPGLs) can relapse after primary treatment. Optimal imaging protocols have not yet been established for posttreatment evaluation. The aim of the present study was to assess the diagnostic value of ¹⁸F-FDOPA PET/CT and MR/CT angiography (MRA/CTA) in HNPGL patients with clinical relapse during their follow-up.

Methods

Sixteen consecutive patients presenting with local pain, tinnitus, dysphagia, hoarse voice, cranial nerve involvement, deafness, or retrotympanic mass appearing during follow-up after the initial treatment of HNPGLs were retrospectively evaluated. Patients underwent both ¹⁸F-FDOPA PET/CT and MRA (15 patents) or CTA (1 patent). Both methods were first assessed under blinded conditions and afterwards correlated. Head and neck imaging abnormalities without histological confirmation were considered true-positive results based on a consensus between radiologists and nuclear physicians and on further ¹⁸F-FDOPA PET/CT and/or MRA.

Results

¹⁸F-FDOPA PET/CT and MRA/CTA were concordant in 14 patients and in disagreement in 2 patients. ¹⁸F-FDOPA PET/CT and MRA/CTA identified, respectively, 12 and 10 presumed recurrent HNPGLs in 12 patients. The two lesions diagnosed by PET/CT only were confirmed during follow-up by otoscopic examination and MRA performed 29 and 17 months later. ¹⁸F-FDOPA PET/CT images were only slightly influenced by the posttreatment sequelae, showing a better interobserver reproducibility than MRA/CTA. Finally, in 2 of the 16 studied patients, ¹⁸F-FDOPA PET/CT detected two additional synchronous primary HNPGLs.

Conclusion

¹⁸F-FDOPA PET/CT is highly sensitive in posttreatment evaluation of patients with HNPGLs, and also offers better interobserver reproducibility than MRA/CTA and whole-body examination. We therefore suggest that ¹⁸F-FDOPA PET/CT is performed as the first diagnostic imaging modality in symptomatic patients with suspicion of HNPGL relapse after primary treatment when ⁶⁸Ga-labeled somatostatin analogues are not available.

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Outcomes of an inpatient refeeding protocol in youth with anorexia nervosa: Rady Children’s Hospital San Diego/University of California, San Diego

Abstract

Background

Current guidelines for nutritional rehabilitation in hospitalized restrictive eating disorder patients recommend a cautious approach to refeeding. Several studies suggest that higher calorie diets may be safe and effective, but have traditionally excluded severely malnourished patients. The goal of this study was to evaluate the safety of a higher calorie nutritional rehabilitation protocol (NRP) in a broad sample of inpatients with restrictive eating disorders, including those who were severely malnourished.

Methods

A retrospective chart review was conducted among eating disorder inpatients between January 2015 and March 2016. Patients were started on a lower calorie diet (≤1500 kcals/day) or higher calorie diet (≥1500 kcals/day). Calorie prescription on admission was based on physician clinical judgement. The sample included patients aged 8–20 years with any DSM-5 restrictive eating disorder. Those who were severely malnourished (<75% expected body weight [EBW]) or required tube feeding during admission were included. Multivariable regression models were used to determine whether level of nutritional rehabilitation was associated with hypophosphatemia, hypomagnesemia, or hypokalemia.

Results

The sample included 87 patients; mean age was 14.4 years (S.D. 32.7); 29% were <75% EBW. The majority (75.8%) was started on higher calorie diets (mean 1781 kcal/day). Controlling for rate of calorie change, initial %EBW, age, race/ethnicity, insurance, diagnosis, and NG/NJ tube placement, higher calorie diets were not associated with hypophosphatemia, hypomagnesemia, or hypokalemia on admission or within the first 72 h. Increased risk of hypophosphatemia on admission was associated with lower baseline %EBW.

Conclusion

A higher calorie NRP was tolerated in this broad population of inpatients with restrictive eating disorders. Lower %EBW on admission was a more important predictor of hypophosphatemia than initial calorie level. Larger studies are required to demonstrate the safety of higher calorie diets in severely malnourished patients.

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Happy New Year from the ATA

The post Happy New Year from the ATA appeared first on American Thyroid Association.

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Editorial Board

Publication date: January 2017
Source:Dental Materials, Volume 33, Issue 1





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Surface modified zeolite-based granulates for the sustained release of diclofenac sodium

Publication date: 1 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 99
Author(s): Carla Serri, Bruno de Gennaro, Vincenzo Quagliariello, Rosario Vincenzo Iaffaioli, Giuseppe De Rosa, Lilia Catalanotti, Marco Biondi, Laura Mayol
In this study, a granulate for the oral controlled delivery of diclofenac sodium (DS), an anionic sparingly soluble nonsteroidal anti-inflammatory drug, has been realized by wet granulation, using a surface modified natural zeolite (SMNZ) as an excipient. The surface modification of the zeolite has been achieved by means of a cationic surfactant, so as to allow the loading of DS through ionic interaction and bestow a control over the drug release mechanism. The granules possessed a satisfactory dosage uniformity, a flowability suitable for an oral dosage form manufacturing, along with a sustained drug release up to 9h, driven by both ion exchange and transport kinetics. Furthermore, the obtained granulate did not elicit a significant cytotoxicity and could also induce a prolonged anti-inflammatory effect on RAW264.7 cells. Taking also into account that natural zeolites are generally abundant and economic, SMNZ can be considered as an attracting alternative excipient for the production of granules with sustained release features.

Graphical abstract

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Towards prostate cancer gene therapy: Development of a chlorotoxin-targeted nanovector for toxic (melittin) gene delivery

Publication date: 1 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 99
Author(s): Zahra Tarokh, Hossein Naderi-Manesh, Mahboobeh Nazari
Prostate cancer is the second leading cause of death due to cancer in men. Owing to shortcomings in the current treatments, other therapies are being considered. Toxic gene delivery is one of the most effective methods for cancer therapy. Cationic polymers are able to form stable nanoparticles via interaction with nucleic acids electrostatically. Branched polyethylenimine that contains amine groups has notable buffering capacity and the ability to escape from endosome through the proton sponge effect. However, the cytotoxicity of this polymer is high, and modification is one of the applicable strategies to overcome this problem. In this study, PEI was targeted with chlorotoxin (CTX) via N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) cross-linker. CTX can bind specifically to matrix metalloproteinase-2 that is overexpressed in certain cancers. Melittin as the major component of bee venom has been reported to have anti-cancer activity. This was thus selected to deliver to PC3 cell line. Flow cytometry analysis revealed that transfection efficiency of targeted nanoparticles is significantly higher compared to non-targeted nanoparticles. Targeted nanoparticles carrying the melittin gene also decreased cell viability of PC3 cells significantly while no toxic effects were observed on NIH3T3 cell line. Therefore, CTX-targeted nanoparticles carrying the melittin gene could serve as an appropriate gene delivery system for prostate and other MMP-2 positive cancer cells.

Graphical abstract

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Drug-drug cocrystals of antituberculous 4-aminosalicylic acid: Screening, crystal structures, thermochemical and solubility studies

Publication date: 1 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 99
Author(s): Ksenia V. Drozd, Alex N. Manin, Andrei V. Churakov, German L. Perlovich
Experimental multistage cocrystal screening of the antituberculous drug 4-aminosalicylic acid (PASA) has been conducted with a number of coformers (pyrazinamide (PYR), nicotinamide (NAM), isonicotinamide (iNAM), isoniazid (INH), caffeine (CAF) and theophylline (TPH)). The crystal structures of 4-aminosalicylic acid cocrystals with isonicotinamide ([PASA+iNAM] (2:1)) and methanol solvate with caffeine ([PASA+CAF+MeOH] (1:1:1)) have been determined by single X-ray diffraction experiments. For the first time for PASA cocrystals it has been found that the structural unit of the [PASA+iNAM] cocrystal (2:1) is formed by 2 types of heterosynthons: acid-pyridine and acid-amide. The desolvation study of the [PASA+CAF+MeOH] cocrystal solvate (1:1:1) has been conducted. The correlation models linking the melting points of the cocrystals with the melting points of the coformers used in this paper have been developed. The thermochemical and solubility properties for all the obtained cocrystals have been studied. Cocrystallization has been shown to lead not only to PASA solubility improving but also to its higher stability against the chemical decomposition.

Graphical abstract

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Upper Extremity Blood Pressure Difference in Patients Undergoing Carotid Revascularisation

Publication date: Available online 3 January 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): A. Huibers, J. Hendrikse, M.M. Brown, S.A. Pegge, M. Arnold, F.L. Moll, L.J. Kapelle, G.J. de Borst
IntroductionBlood pressure (BP) regulation is important in patients with carotid artery atherosclerotic disease. Concomitant subclavian artery stenosis (SAS) might lead to an underestimation of the true systemic BP in the monitoring of these patients. This study aimed to assess the prevalence of the inter-arm BP difference in patients undergoing carotid intervention and its association with ipsilateral significant subclavian stenosis and clinical outcome.MethodsBilateral BP measurements and vascular imaging (CTA and MRA) of both subclavian arteries and the innominate artery were assessed in 182 symptomatic patients with carotid artery stenosis undergoing revascularisation in the International Carotid Stenting Study (ICSS). Data were separately analysed according to previously described cutoff values for systolic BP (SBP) differences of ≥10 and <15 mmHg, ≥15 and <20 mmHg, or ≥20 mmHg. Significant SAS was defined as a >50% diameter reduction.ResultsOf the 182 patients, 39 (21%) showed an inter-arm difference in SBP >15 mmHg. The mean inter-arm SBP difference associated with ipsilateral SAS was 14 mmHg. SAS was present in 21/182 (12%) patients. Only two patients (1%) had bilateral stenotic disease. An inter-arm SBP difference of ≥20 mmHg was associated with unilateral SAS (RR 11.8; 95% CI 3.2–43.1) with a sensitivity of 23% and a specificity of 98%. Patients were followed up for a median of 4.0 years (IQR 3.0–6.0; maximum 7.5). Risk of stroke or death during follow-up was 20.0% (95% CI 11.1–28.9) in patients with, and 15.1% (95% CI 12.3–17.9) in patients without SAS (p = .561). The hospital stay was longer in patients with significant SAS (5.0 days, SD 4.9 vs. 2.7 days, SD 4.3, p = .035).ConclusionThe present study is the first to affirm the clinical need for the measurement of inter-arm BP differences in patients undergoing carotid revascularisation, especially in the post-operative phase in the prevention of cerebral hyperperfusion.



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Highly efficient photocatalytic performances of SnO2-deposited ZnS nanorods based on interfacial charge transfer

Publication date: 15 May 2017
Source:Applied Catalysis B: Environmental, Volume 205
Author(s): Jaewon Lee, Yeonho Kim, Joon Ki Kim, Seongchan Kim, Dal-Hee Min, Du-Jeon Jang
SnO2/ZnS nanocomposites of SnO2 quantum dots (QDs)-deposited ZnS nanorods having highly enhanced photocatalytic activity and photostability have been fabricated via a facile two-step hydrazine-assisted hydrothermal process without involving any surface treatments. The photocatalytic activity of SnO2/ZnS nanocomposites with a Sn-to-Zn molar ratio (RSn/Zn) of 0.1 is 3 times higher than that of pristine ZnS nanorods and 17 times higher than that of commercial ZnS. The incorporation of SnO2 QDs increases the photocatalytic efficiency of ZnS nanorods due to the following reasons: photogenerated charge carriers are readily separated owing to type II band configuration and direct contact at interfaces without having any linker molecules; active surface sites are increased to adsorb more dye molecules; the light absorption range is extended to the visible region, generating more charge carriers on the surfaces of heterojunction structures. The decay time, as well as the intensity, of the band-edge emission of SnO2/ZnS nanocomposites at 325nm decreases progressively and rapidly with the increase of RSn/Zn, indicating that fast electron transfer takes place from photoexcited ZnS nanorods to SnO2 QDs. Thus, the higher photocatalytic degradation efficiencies of SnO2/ZnS nanocomposites are considered to result mainly from the increased separation rates of photogenerated charges. The photostability of SnO2/ZnS nanocomposites is also improved due to the protection and charge-separation effects of decorating SnO2 QDs. Our prepared SnO2/ZnS nanocomposites are suggested to have great potential for photodegradation nanocatalysts in the field of waste-water treatment.

Graphical abstract

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Cu2ZnSnS4 thin films obtained by sulfurization of evaporated Cu2SnS3 and ZnS layers: Influence of the ternary precursor features

Publication date: 1 April 2017
Source:Applied Surface Science, Volume 400
Author(s): V. Robles, C. Guillén, J.F. Trigo, J. Herrero
Cu2ZnSnS4 (CZTS) thin films have been grown by sulfurization of Cu2SnS3 (CTS) and ZnS layers evaporated on glass substrates. Four CTS precursor films have been tested, with two different atomic compositions (Cu/Sn=1.7 and Cu/Sn=2.1) and substrate temperatures (350 and 450°C), together with analogous ZnS layers deposited by maintaining the substrate at 200°C. The sulfurization of the CTS and ZnS stacked layers was performed at 500°C during 1h. The evolution of the crystalline structure, morphology, optical and electrical properties from each CTS precursor to the CZTS compound has been studied, especially the influence of the ternary precursor features on the quaternary film characteristics. The kesterite structure has been identified after sulfurization of the various samples, with main (112) orientation and mean crystallite sizes S112=40–56nm, being higher for the Cu-poor compositions. The CZTS average roughness has varied in a wide interval Ra=8–66nm, being directly related to the CTS precursor layer, which becomes rougher for a higher deposition temperature or Cu content. Besides, the band gap energy and the electrical resistivity of the CZTS films have changed in the ranges Eg=1.54–1.64eV and ρ=0.2–40Ωcm, both decreasing when the Cu content and/or the surface roughness increase.

Graphical abstract

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Vineland-II adaptive behavior profile of children with attention-deficit/hyperactivity disorder or specific learning disorders

Publication date: February 2017
Source:Research in Developmental Disabilities, Volume 61
Author(s): Giulia Balboni, Oriana Incognito, Carmen Belacchi, Sabrina Bonichini, Roberto Cubelli
BackgroundThe evaluation of adaptive behavior is informative in children with attention-deficit/hyperactivity disorder (ADHD) or specific learning disorders (SLD). However, the few investigations available have focused only on the gross level of domains of adaptive behavior.AimsTo investigate which item subsets of the Vineland-II can discriminate children with ADHD or SLD from peers with typical development.Methods and proceduresStudent's t-tests, ROC analysis, logistic regression, and linear discriminant function analysis were used to compare 24 children with ADHD, 61 elementary students with SLD, and controls matched on age, sex, school level attended, and both parents' education level.ResultsSeveral item subsets that address not only ADHD core symptoms, but also understanding in social context and development of interpersonal relationships, allowed discrimination of children with ADHD from controls. The combination of four item subsets (Listening and attending, Expressing complex ideas, Social communication, and Following instructions) classified children with ADHD with both sensitivity and specificity of 87.5%. Only Reading skills, Writing skills, and Time and dates discriminated children with SLD from controls.ConclusionsEvaluation of Vineland-II scores at the level of item content categories is a useful procedure for an efficient clinical description.



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Myocardial blood flow and left ventricular functional reserve in hypertrophic cardiomyopathy: a 13 NH 3 gated PET study

Abstract

Introduction

Ischemia in hypertrophic cardiomyopathy (HCM) is caused by coronary microvascular dysfunction (CMD), which is detected by measuring myocardial blood flow (MBF) with PET. Whether CMD may be associated with ischemic left ventricular (LV) dysfunction is unclear. We therefore assessed LV ejection fraction (EF) reserve in HCM patients undergoing dipyridamole (Dip) PET.

Methods

Resting and stress ¹³NH₃ dynamic as well as gated PET were performed in 34 HCM patients. Segmental MBF and transmural perfusion gradient (TPG = subendocardial / subepicardial MBF) were assessed. LVEF reserve was considered abnormal if Dip LVEF decreased more than 5 units as compared to rest.

Results

Eighteen patients had preserved (group A) and 16 abnormal LVEF reserve (group B; range −7 to −32). Group B patients had greater wall thickness than group A, but resting volumes, LVEF, resting and Dip MBF, and myocardial flow reserve were similar. Group B had slightly higher summed stress score and summed difference score in visual analysis than group A, and a significantly higher summed stress wall motion score. In group B, resting TPG was slightly lower (1.31 ± 0.29 vs. 1.37 ± 0.34, p <0.05), and further decreased after Dip, whilst in group A it increased (B = 1.20 ± 0.39, p < 0.0001 vs. rest and vs. A = 1.40 ± 0.43). The number of segments per patient with TPG <1 was higher than in group A (p < 0.001) and was a significant predictor of impaired LVEF reserve (OR 1.86, p < 0.02), together with wall thickness (OR 1.3, p < 0.02).

Conclusion

Abnormal LVEF response is common in HCM patients following Dip, and is related to abnormal TPG, suggesting that subendocardial ischemia might occur under Dip and cause transient LV dysfunction. Although in vivo this effect may be hindered by the adrenergic drive associated with effort, these findings may have relevance in understanding exercise limitation and heart failure symptoms in HCM.

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Executive Function Performance and Change in Aging is Predicted by Apolipoprotein E, Intensified by Catechol-O-methyltransferase and Brain-derived neurotrophic factor, and Moderated by Age and Lifestyle

Publication date: Available online 3 January 2017
Source:Neurobiology of Aging
Author(s): Shraddha Sapkota, Lars Bäckman, Roger A. Dixon
Recent studies have reported several genetic, health, and aging interaction effects in predicting cognitive performance and change. We used an accelerated longitudinal design to examine interactions among genetic, lifestyle, and aging for executive function (EF) in non-demented older adults (n=634; age range=53-95 years). The polymorphisms were Apolipoprotein E (APOE),Catechol-O-methyl transferase (COMT), and Brain-derived neurotrophic factor (BDNF). We tested (a) independent and additive effects of APOE, COMT, and BDNF and (b) APOE effect modification for COMT+ BDNF, on EF performance and 9-year change as separated by age and lifestyle activities. First, APOE ε4+ carriers had poorer EF performance and steeper 9-year decline. Second, APOE ε4+ carriers with (a) BDNF Met/Met genotype and (b) increasing allelic risk in the COMT+ BDNF risk panel had poorer EF performance; these effects were moderated by lifestyle activities (composite of everyday social, physical, cognitive activities). Examining APOE effect modification for COMT+ BDNF risk panel effects with other moderating factors may help identify complex neurobiological and genetic underpinnings of polygenic phenotypes such as EF in aging.



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Administrations of human adult ischemia-tolerant mesenchymal stem cells and factors reduce amyloid beta pathology in a mouse model of Alzheimer's disease

Publication date: March 2017
Source:Neurobiology of Aging, Volume 51
Author(s): Taoufiq Harach, Fabien Jammes, Charles Muller, Nicolas Duthilleul, Victoria Cheatham, Valentin Zufferey, David Cheatham, Yelizaveta A. Lukasheva, Theo Lasser, Tristan Bolmont
The impact of human adult ischemia-tolerant mesenchymal stem cells (hMSCs) and factors (stem cell factors) on cerebral amyloid beta (Aβ) pathology was investigated in a mouse model of Alzheimer's disease (AD). To this end, hMSCs were administered intravenously to APPPS1 transgenic mice that normally develop cerebral Aβ. Quantitative reverse transcriptase polymerase chain reaction biodistribution revealed that intravenously delivered hMSCs were readily detected in APPPS1 brains 1 hour following administration, and dropped to negligible levels after 1 week. Notably, intravenously injected hMSCs that migrated to the brain region were localized in the cerebrovasculature, but they also could be observed in the brain parenchyma particularly in the hippocampus, as revealed by immunohistochemistry. A single hMSC injection markedly reduced soluble cerebral Aβ levels in APPPS1 mice after 1 week, although increasing several Aβ-degrading enzymes and modulating a panel of cerebral cytokines, suggesting an amyloid-degrading and anti-inflammatory impact of hMSCs. Furthermore, 10 weeks of hMSC treatment significantly reduced cerebral Aβ plaques and neuroinflammation in APPPS1 mice, without increasing cerebral amyloid angiopathy or microhemorrhages. Notably, a repeated intranasal delivery of soluble factors secreted by hMSCs in culture, in the absence of intravenous hMSC injection, was also sufficient to diminish cerebral amyloidosis in the mice. In conclusion, this preclinical study strongly underlines that cerebral amyloidosis is amenable to therapeutic intervention based on peripheral applications of hMSC or hMSC factors, paving the way for a novel therapy for Aβ amyloidosis and associated pathologies observed in AD.



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Quercetin-3-O-glucuronide promotes the proliferation and migration of neural stem cells

Publication date: Available online 3 January 2017
Source:Neurobiology of Aging
Author(s): Samrat Baral, Ramesh Pariyar, Jaehyo Kim, Ho-Sub Lee, Jungwon Seo
Quercetin is a bioactive compound exerting therapeutic effects on in-vivo animal models of neurodegeneration or neurotoxicity. However, the narrow therapeutic dose-range of quercetin has been a point of concern since previous studies have demonstrated that quercetin induces cytotoxicity in vitro. Quercetin is metabolized to quercetin glucuronates such as quercetin-3-O-glucuronide (Q3GA), primarily detected in the plasma and the brain. Here, we examined whether and how quercetin or Q3GA regulates neural stem cells (NSCs) in vivo and in vitro. Immunohistochemistry showed that oral administration of quercetin increased nestin-, DCX-, BrdU/DCX-, and BrdU/NeuN-positive cells in the DG of mice. However, quercetin decreased the viability of human embryonic NSCs in culture, accompanied by decreased Akt phosphorylation and increased cleavage of caspase-3 and PARP. In contrast, Q3GA increased BrdU-positive cell proliferation, Akt phosphorylation and cyclin D1 expression. PI3K/Akt inhibitor LY294002 reversed Q3GA-induced Akt phosphorylation and cyclin D1 expression, thereby reducing Q3GA-induced proliferation. Furthermore, Q3GA increased the protein secretion of BDNF and its blockade using anti-BDNF antibody reversed Q3GA-induced proliferation. Under differentiation state, Q3GA promotes NSC migration, along with increased mRNA expression of CXCR4. Moreover, Q3GA significantly reversed scopolamine-induced reduction of Akt phosphorylation in the mouse hippocampus and ameliorated scopolamine-induced memory impairments. Our results demonstrate that quercetin and its metabolite Q3GA control NSC viability in a converse manner through contrary regulation of Akt, accounting for the conflicting effects of quercetin in vivo and in vitro. This study provides a novel mechanism for the positive effects of Q3GA on neurogenesis and suggests its therapeutic potential in neurodegenerative diseases.

Graphical abstract

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