Beyond the Paradigm: Combining Mass Spectrometry and Nuclear Magnetic Resonance for Metabolomics

Publication date: Available online 11 January 2017
Source:Progress in Nuclear Magnetic Resonance Spectroscopy
Author(s): Darrell D. Marshall, Robert Powers
Metabolomics is undergoing tremendous growth and is being employed to solve a diversity of biological problems from environmental issues to the identification of biomarkers for human diseases. Nuclear magnetic resonance (NMR) and mass spectrometry (MS) are the analytical tools that are routinely, but separately, used to obtain metabolomics data sets due to their versatility, accessibility, and unique strengths. NMR requires minimal sample handling without the need for chromatography, is easily quantitative, and provides multiple means of metabolite identification, but is limited to detecting the most abundant metabolites (⩾ 1 μM). Conversely, mass spectrometry has the ability to measure metabolites at very low concentrations (femtomolar to attomolar) and has a higher resolution (∼10³-10⁴) and dynamic range (∼10³-10⁴), but quantitation is a challenge and sample complexity may limit metabolite detection because of ion suppression. Consequently, liquid chromatography (LC) or gas chromatography (GC) is commonly employed in conjunction with MS, but this may lead to other sources of error. As a result, NMR and mass spectrometry are highly complementary, and combining the two techniques is likely to improve the overall quality of a study and enhance the coverage of the metabolome. While the majority of metabolomic studies use a single analytical source, there is a growing appreciation of the inherent value of combining NMR and MS for metabolomics. An overview of the current state of utilizing both NMR and MS for metabolomics will be presented.

Graphical abstract

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Molecular biomarkers to predict response to neoadjuvant chemotherapy for bladder cancer

Publication date: Available online 11 January 2017
Source:Cancer Treatment Reviews
Author(s): Consuelo Buttigliero, Marcello Tucci, Francesca Vignani, Giorgio V. Scagliotti, Massimo Di Maio
Cystectomy is the gold standard for treatment of localized muscle-invasive bladder cancer. However, about 50% of patients develop metastases within 2 years after cystectomy and subsequently die for the disease. Neoadjuvant cisplatin-based chemotherapy before cystectomy improves the overall survival in patients with muscle-invasive bladder cancer, and pathological response to neoadjuvant treatment (downstaging to ⩽pT1 at cystectomy) is a strong predictor of better disease-specific survival. Nevertheless, some patients do not benefit from neoadjuvant therapy. The identification of reliable biomarkers that could enable the clinicians to identify patients who will really benefit from neoadjuvant chemotherapy is a major issue. This approach could lead to individualized therapy, in order to optimize the chance of response, avoiding the impact of neoadjuvant treatment on quality of life and the delay of cystectomy in non-responder patients. However, no molecular predictive biomarkers have shown clinical utility.This paper aims to review currently available data about biomarkers predictive of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer.



http://ift.tt/2iEdK1r

Robust Estimation of Carotid Artery Wall Motion Using the Elasticity-based State-space Approach

Publication date: Available online 10 January 2017
Source:Medical Image Analysis
Author(s): Zhifan Gao, Huahua Xiong, Xin Liu, Heye Zhang, Dhanjoo Ghista, Wanqing Wu, Shuo Li
The dynamics of the carotid artery wall has been recognized as a valuable indicator to evaluate the status of atherosclerotic disease in the preclinical stage. However, it is still a challenge to accurately measure this dynamics from ultrasound images. This paper aims at developing an elasticity-based state-space approach for accurately measuring the two-dimensional motion of the carotid artery wall from the ultrasound imaging sequences. In our approach, we have employed a linear elasticity model of the carotid artery wall, and converted it into the state space equation. Then, the two-dimensional motion of carotid artery wall is computed by solving this state-space approach using the H∞ filter and the block matching method. In addition, a parameter training strategy is proposed in this study for dealing with the parameter initialization problem. In our experiment, we have also developed an evaluation function to measure the tracking accuracy of the motion of the carotid artery wall by considering the influence of the sizes of the two blocks (acquired by our approach and the manual tracing) containing the same carotid wall tissue and their overlapping degree. Then, we have compared the performance of our approach with the manual traced results drawn by three medical physicians on 37 healthy subjects and 103 unhealthy subjects. The results have showed that our approach was highly correlated (Pearson's correlation coefficient equals 0.9897 for the radial motion and 0.9536 for the longitudinal motion), and agreed well (width the 95% confidence interval is 89.62 μm for the radial motion and 387.26 μm for the longitudinal motion) with the manual tracing method. We also compared our approach to the three kinds of previous methods, including conventional block matching methods, Kalman-based block matching methods and the optical flow. Altogether, we have been able to successfully demonstrate the efficacy of our elasticity-model based state-space approach (EBS) for more accurate tracking of the 2-dimensional motion of the carotid artery wall, towards more effective assessment of the status of atherosclerotic disease in the preclinical stage.

Graphical abstract

http://ift.tt/2iey74i

A Framework for Analysis of Linear Ultrasound Videos to Detect Fetal Presentation and Heartbeat

Publication date: Available online 10 January 2017
Source:Medical Image Analysis
Author(s): M.A. Maraci, C.P. Bridge, R. Napolitano, A. Papageorghiou, J.A. Noble
Confirmation of pregnancy viability (presence of fetal cardiac activity) and diagnosis of fetal presentation (head or buttock in the maternal pelvis) are the first essential components of ultrasound assessment in obstetrics. The former is useful in assessing the presence of an on-going pregnancy and the latter is essential for labour management. We propose an automated framework for detection of fetal presentation and heartbeat from a predefined free-hand ultrasound sweep of the maternal abdomen. Our method exploits the presence of key anatomical sonographic image patterns in carefully designed scanning protocols to develop, for the first time, an automated framework allowing novice sonographers to detect fetal breech presentation and heartbeat from an ultrasound sweep. The framework consists of a classification regime for a frame by frame categorization of each 2D slice of the video. The classification scores are then regularized through a conditional random field model, taking into account the temporal relationship between the video frames. Subsequently, if consecutive frames of the fetal heart are detected, a kernelized linear dynamical model is used to identify whether a heartbeat can be detected in the sequence. In a dataset of 323 predefined free-hand videos, covering the mother's abdomen in a straight sweep, the fetal skull, abdomen, and heart were detected with a mean classification accuracy of 83.4%. Furthermore, for the detection of the heartbeat an overall classification accuracy of 93.1% was achieved.

Graphical abstract

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Remarks about “A pediatric patient of hemorrhagic acute transverse myelitis”

Publication date: Available online 11 January 2017
Source:Brain and Development
Author(s): Daniele Coraci, Valter Santilli, Silvia Giovannini, Luca Padua




http://ift.tt/2j4x4YL

Reply to the remarks about “A pediatric patient of hemorrhagic acute transverse myelitis”

Publication date: Available online 11 January 2017
Source:Brain and Development
Author(s): Masataka Fukuoka, Ichiro Kuki, Hisashi Kawawaki, Kiyohiro Kim, Yuka Hattori, Hitomi Tsuji, Asako Horino, Megumi Nukui, Shin Okazaki




http://ift.tt/2jhnUWJ

Bilateral blepharoptosis in a juvenile

Publication date: Available online 10 January 2017
Source:Brain and Development
Author(s): Hiroshi Yamaguchi, Tsukasa Tanaka, Daisaku Toyoshima, Azusa Maruyama, Akihiro Ichinose, Hiroaki Nagase
In adults, aponeurotic blepharoptosis is the most common type of ptosis. However, myogenic ptosis is the predominant cause, and bilateral aponeurotic ptosis is very rare among children. Here, we report a previously healthy 10-year-old Japanese girl with bilateral aponeurotic blepharoptosis who presented initially with bilateral blepharoptosis for about 4years. This case report shows that history taking and careful observation of the patient lead to an accurate diagnosis, and aponeurotic ptosis should be considered in the differential diagnosis of bilateral blepharoptosis among children.



http://ift.tt/2j4bWlt

Epigenetic modifications and epigenetic based medication implementations of autoimmune diseases

Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Majid Ahmadi, Tohid Gharibi, Sanam Dolati, Davood Rostamzadeh, Saeed Aslani, Behzad Baradaran, Vahid Younesi, Mehdi Yousefi
Recent genome-wide association studies have documented a number of genetic variants to explain mechanisms underlying autoimmune diseases. However, the precise etiology of autoimmune diseases remains largely unknown. Epigenetic mechanisms like alterations in the post-translational modification of histones and DNA methylation may potentially cause a breakdown of immune tolerance and the perpetuation of autoreactive responses. Recently, several studies both in experimental models and clinical settings proposed that the epigenome may hold the key to a better understanding of autoimmunity initiation and perpetuation. More specifically, data support the impact of epigenetic changes in autoimmune diseases, in some cases based on mechanistical observations. Epigenetic therapy already being employed in hematopoietic malignancies may also be associated with beneficial effects in autoimmune diseases. In this review, we will discuss on what we know and expect about the treatment of autoimmune disease based on epigenetic aberrations.



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Familial gastrointestinal stromal tumors, lentigines, and café-au-lait macules associated with germline c-kit mutation treated with imatinib

Abstract

Background

Familial lentiginosis syndromes are characterized by a wide array of manifestations resulting from activation of molecular pathways which control growth, proliferation, and differentiation of a broad range of tissues. Familial gastrointestinal stromal tumors (GISTs) are often accompanied by additional features like hyperpigmentation, mastocytosis, and dysphagia. They have been described with mutations in c-kit (most commonly), platelet-derived growth factor receptor A, neurofibromatosis-1, and succinate dehydrogenase genes.

Materials and Methods

We report on molecular characterization and tumor histopathology of two siblings in whom lentigines and café-au-lait macules were present along with multifocal GIST. Immuhistochemical analysis of CD34 and CD117 was performed on GIST biopsy samples from both siblings, while c-kit mutational analysis was done by PCR and direct sequencing on DNA from peripheral blood leukocytes of all family members and from paraffin-embedded gastric biopsy specimens of affected siblings.

Results

Histopathology revealed positive expression of CD117 and CD34. Mutational analysis showed the germline c.1676T>C mutation in c-kit exon 11, (p.(Val559Ala)), in the peripheral blood of both siblings and a second exon 11 mutation, c.1669T>A (p.(Trp557Arg)) in the tumor biopsy of one of them. Initiation of imatinib treatment resulted in striking resolution of their hyperpigmentation and a stable gastrointestinal disease in one of them.

Conclusions

A c-kit mutational test in familial GISTs is indicated before initiation of imatinib therapy, as it can help predict tumor response to treatment.

http://ift.tt/2ibRfor

Protective effects of tacalcitol against oxidative damage in human epidermal melanocytes

Abstract

Background

Oxidative damage may lead to the dysfunction of melanocytes (MCs) and is one of the causative mechanisms involved in the pathogenesis of vitiligo.

Objectives

This study was designed to investigate the protective effects of the vitamin D3 analog tacalcitol on oxidative damage induced by hydrogen peroxide (H₂O₂) in human epidermal MCs.

Methods

Human epidermal MCs were cultured and identified by l-DOPA staining and HMB-45 immunohistochemical staining. The model of oxidative damage induced by H₂O₂ was established, and the cells were treated with tacalcitol. The viability of MCs was determined using an MTS assay. Morphological changes in cell dendrites were observed by microscopy, and the rate of change of dendrites was calculated. The reactive oxygen species (ROS) level in MCs was determined using immunofluorescence microscopy. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in MCs were determined using the WST-1 and TBA methods, respectively.

Results

In comparison with the control group, the viability of MCs and SOD activity were significantly decreased in the H₂O₂ group (P < 0.05) and significantly increased in the tacalcitol group (P < 0.05). In comparison with the control group, the rate of change of cell dendrites and levels of ROS and MDA were significantly increased in the H₂O₂ group (P < 0.05) and significantly decreased in the tacalcitol group (P < 0.05).

Conclusions

Tacalcitol can reduce oxidative damage induced by H₂O₂ in MCs by inhibiting intracellular ROS overproduction, increasing SOD activity, and decreasing the level of MDA, thereby reducing cell apoptosis.

http://ift.tt/2iZYCMO

Risk factors for nonmelanoma skin cancer in renal transplant recipients: a case–control study from a reference outpatient clinic in Southeast Brazil

Abstract

Background

Nonmelanoma skin cancer (NMSC) is the most common tumor in humans, and its incidence increases among renal transplant recipients (RTRs). The aims of this study were to characterize the RTRs with NMSC, to identify risk factors, and to calculate the probability of this tumor in this population.

Methods

This was a hospital-based case–control study. Epidemiological and clinical variables were evaluated. Hierarchical logistic regression was used, and a mathematical model was built.

Results

In total, 245 subjects were included. Possible associations were identified using a univariate analysis. Multivariate analysis identified risk factors with respective odds ratios and confidence intervals (95% CI): males 2.5 (1.3–4.7), age over 50 years 5.4 (2.3–12.9), Fitzpatrick's skin phototypes I–III 3.7 (1.6–8.7), occupational sun exposure 4.1 (2.1–8.1), timetable of recreational sun exposure all day 3.0 (1.4–6.1), and duration of transplantation (80 months or more) 3.3 (1.6–6.5). The Hosmer-Lemeshow test and the receiver operating characteristics curve showed a strong fit and accuracy, respectively. The probability of an NMSC ranged from less than 1 to 92.5%.

Conclusions

This study characterized the RTRs with NMSC and identified risk factors. The multivariate analysis by hierarchical logistic regression proved to be a useful tool and allowed for the determination of the probability of NMSC in this population.

http://ift.tt/2ibCPEU

Narcissus’ reflection: toxic ingredients in cosmetics through the ages

http://ift.tt/2iZXyc6

Issue Information - TOC

http://ift.tt/2ibBAph

Trichoscopic clues for diagnosis of alopecia areata and trichotillomania in Asians

Abstract

Background

Trichoscopy has become a useful diagnostic tool for various hair and scalp diseases, including alopecia areata (AA) and trichotillomania (TTM), which are sometimes difficult to distinguish clinically.

Objectives

To describe trichoscopic findings of AA and TTM in an Asian population and to establish diagnostic clues for these conditions.

Methods

Trichoscopy was performed with a handheld dermoscope in 52 patients diagnosed with AA and 23 patients diagnosed with TTM. Trichoscopic images were then blindly evaluated.

Results

The trichoscopic features more frequently observed in AA than in TTM included exclamation mark hairs (AA 59.6%, TTM 26.1%), tapered hairs (AA 59.6%, TTM 4.3%), yellow dots (AA 46.2%, TTM 21.7%), and angulated hairs (AA 26.9%, TTM 0%) (P < 0.05). On the other hand, broken hairs of different lengths (TTM 100%, AA 3.8%), trichoptilosis (TTM 78.3%, AA 5.8%), V-sign (TTM 43.5%, AA 3.8%), flame hairs (TTM 43.5%, AA 0%), and hair powder (TTM 13%, AA 1.9%) were more commonly demonstrated in TTM than in AA (P < 0.05).

Conclusions

Exclamation mark hairs indicate a diagnosis of AA but not pathognomonic. In addition, angulated hairs, fractured hairs forming a sharp angle along the hair shaft, appear to be typical for AA in Asians when differentiating from TTM. It is important to consider various trichoscopic findings together to establish the diagnosis of AA or TTM.

http://ift.tt/2iZYtsJ

Efficacy of superficial cryotherapy on the eyebrows of patients with alopecia universalis also treated with contact immunotherapy on the scalp: a prospective, split-face comparative study

Abstract

Background

Few treatment modalities are available for treating alopecia areata (AA) of the eyebrow. Due to the anatomical proximity of the eyebrows to the eyes, safety issues and side effects should always be taken into consideration when choosing the treatment modality. This study was designed to examine the efficacy of superficial cryotherapy on patients with AA of the eyebrow.

Methods

Superficial cryotherapy was performed every other week on the right eyebrow (SC-treated) in a total of 20 patients who had been previously treated with diphenylcyclopropenone (DPCP) immunotherapy on the scalp. No specific treatment was performed on the left eyebrows as a control. The degree of eyebrow recovery was compared in 15 patients who continued to receive more than 10 superficial cryotherapy treatments (5 months of treatment) on their right eyebrow.

Results

Hair density was significantly increased on both treated and control eyebrows after 5 months of treatment compared with the pretreatment density; moreover, the SC-treated eyebrows exhibited a significantly greater increase in density than the control eyebrows. Although hair thickness in the control eyebrows did not change significantly over the treatment period, hair thickness of the SC-treated eyebrows showed a statistically significant increase at months 3 and 5.

Conclusions

Superficial cryotherapy is associated with minimal to no adverse events and exhibits high compliance and relatively good efficacy. Thus, this treatment is an important additional option for patients with AA of the eyebrow.

http://ift.tt/2ibKIKC

Assessment of the effectiveness of topical propranolol 4% gel for infantile hemangiomas

Abstract

Background

Infantile hemangiomas (IHs) are the most common vascular tumors in children. Because of their benign character and natural involution, the vast majority of IHs do not require any treatment. In the past few years, topical beta blockers have been reported to be an effective treatment of superficial IHs.

Objective

We sought to evaluate the clinical effectiveness and safety profile of topical propranolol 4% gel for the treatment of IHs.

Methods

A retrospective study of all cases of IHs treated with topical propranolol 4% gel between 2013 and 2015 was performed. All patients were evaluated in a pediatric dermatology unit of a tertiary medical center. Epidemiologic, clinical, and treatment data, including effectiveness score and safety, were reviewed.

Results

The study included 63 patients with a total of 75 IHs. Of the total number of IHs, 43 (57.3%) showed a good response to treatment, 19 (25.3%) a partial response, and 13 (17.33%) poor or no response, thus 62 (82.6%) had good or partial response to treatment. Age at treatment initiation, treatment time, thickness of the superficial component, and size of the lesions were shown to predict response to therapy. Out of the entire examined group, only two patients reported minor local side effects manifested by irritation, redness, and scaling of the treated area. No systemic adverse effects were reported. Limitations: This is an uncontrolled retrospective study.

Conclusion

Propranolol 4% gel is a safe and efficient topical therapy for IH.

http://ift.tt/2iZVZef

Clinical effectiveness of low-level laser treatment on peripheral somatosensory neuropathy

Abstract

Peripheral sensory neuropathy treatment is one of the common treatment problems and causes morbidity and mortality in people suffering from that. Although treatment depends on the underlying cause of the condition, nevertheless, in some cases, there is no cure for it, and it requires palliative and symptomatic treatment. In laboratory studies, low-level laser has been effective in the nerves protection and restoration. The aim of this article is to investigate the clinical efficacy of low-level laser on improvement of the peripheral somatosensory neuropathy. Search in the articles published up to 30 October 2015 (full text and abstracts) in databases PubMed (Medline), Cochrane library, Physiotherapy Evidence Database was performed. The studies of low-level laser trials on patients with peripheral neuropathy were carried out and evaluated in terms of the exclusion criteria. There are 35 articles among which 10 articles had the intended and required criteria. 1, 3, and 6 articles study the patients with diabetes, neuropathy caused by trauma, and carpal tunnel syndrome, respectively. In six studies, laser led to a reduction in sensory impairment and improvement of the physiological function of the sensory nerves. In these articles, lasers (Diode, GaAlAs, He-Ne) had wavelength range 660–860 nm, radiation power 20–250 mW, energy density 0.45–70 J/cm². The intervention sessions range was 6–21 times and patient follow-up was 0–6 months. According to the results of these studies, low-level laser therapy can improve sensory function in patients with peripheral somatosensory neuropathy, although little research have not been done, laser treatment regimens are varied and do not recommend a specific treatment protocol. It seems it requires more research to sum up better, particularly in relation to diabetes.

http://ift.tt/2jh3Cwn

In stage pT1 non-muscle-invasive bladder cancer (NMIBC), high KRT20 and low KRT5 mRNA expression identify the luminal subtype and predict recurrence and survival

Abstract

Differential expression of cytokeratins (CK) is a characteristic feature of chemoresistant luminal (KRT20) and chemosensitive intrinsic aggressive basal (KRT5) subtypes in muscle-invasive bladder cancer (MIBC). We investigated mRNA expression of KRT5 and KRT20 and its predictive value in stage pT1 bladder cancer. In retrospective analysis of clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder, a single-step RT-qPCR was used to measure mRNA expression. Furthermore, immunohistochemical (IHC) staining of CK20, panCK, and MIB1 was performed. Valid measurements were obtained from 231 samples out of a series of 284 patients. Spearman correlation revealed significant associations between mRNA and protein expression of KRT20/CK20 (ρ 0.6096, p < 0.0001) and MKI67/MIB1 (ρ 0.5467, p < 0.0001). A positive correlation was found between MKI67 and KRT20 expression (ρ 0.3492, p < 0.0001), while MKI67 and KRT5 were negatively correlated (ρ −0.1693, p = 0.01). High KRT20 expression (≥40.26) was significantly associated with worse recurrence free survival (RFS) (p = 0.001), progression-free survival (PFS) (p = 0.0003), and cancer specific survival (CSS) (p = 0.0414). The combination of high KRT20 expression and low KRT5 expression (<36.83) was associated with unfavorable RFS (p = 0.0038) and PFS (p = 0.0003) and proved to be the only independent predictor for RFS (p = 0.0055) and PFS (p = 0.0023) in multivariate analysis. KRT20 mRNA determination was superior to CK20 protein estimation with regard to RFS and PFS prediction. KRT20 and KRT5 mRNA quantification can predict recurrence and progression of stage pT1 NMIBC reflecting basal and luminal subtypes of MIBC and is superior to CK20 protein expression determined by IHC.

http://ift.tt/2iZVrVn

Papillary carcinoma thyroid in a thyroglossal cyst: A management dilemma

Volume 2, Issue 1, December 2017, Page 5-10
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http://ift.tt/2j6ebFb

Meningoencephalitis and otitis media in a child with Mycoplasma pneumoniae infection

Volume 2, Issue 1, December 2017, Page 1-4
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http://ift.tt/2j6sPMH

Clinical Thyroidology for the Public – Highlighted Article

From Clinical Thyroidology for the Public: Hypothyroidism (underactive thyroid) is very common, especially in women and is diagnosed most of the time by an increased TSH level. Read More….

The post Clinical Thyroidology for the Public – Highlighted Article appeared first on American Thyroid Association.

http://ift.tt/2jh9XIl

Clinical Thyroidology for the Public – Highlighted Article

From Clinical Thyroidology for the Public: Hypothyroidism (underactive thyroid) is very common, especially in women and is diagnosed most of the time by an increased TSH level. Read More….

The post Clinical Thyroidology for the Public – Highlighted Article appeared first on American Thyroid Association.

http://ift.tt/2jh9XIl

“The effect of conventional and transparent surgical masks on speech understanding in individuals with and without hearing loss” by Atcherson et al

http://ift.tt/2j6cPKK

Binaural Interference and the Effects of Age and Hearing Loss

http://ift.tt/2jtcCxK

Noise Exposure Questionnaire: A Tool for Quantifying Annual Noise Exposure

http://ift.tt/2j68wPN

Detailed Audiological Evaluation of a Patient with Xeroderma Pigmentosum with Neural Degeneration

http://ift.tt/2jt9RN1

BDNF gene delivery mediated by neuron-targeted nanoparticles is neuroprotective in peripheral nerve injury

Publication date: March 2017
Source:Biomaterials, Volume 121
Author(s): Cátia D.F. Lopes, Nádia P. Gonçalves, Carla P. Gomes, Maria J. Saraiva, Ana P. Pêgo
Neuron-targeted gene delivery is a promising strategy to treat peripheral neuropathies. Here we propose the use of polymeric nanoparticles based on thiolated trimethyl chitosan (TMCSH) to mediate targeted gene delivery to peripheral neurons upon a peripheral and minimally invasive intramuscular administration. Nanoparticles were grafted with the non-toxic carboxylic fragment of the tetanus neurotoxin (HC) to allow neuron targeting and were explored to deliver a plasmid DNA encoding for the brain-derived neurotrophic factor (BDNF) in a peripheral nerve injury model. The TMCSH-HC/BDNF nanoparticle treatment promoted the release and significant expression of BDNF in neural tissues, which resulted in an enhanced functional recovery after injury as compared to control treatments (vehicle and non-targeted nanoparticles), associated with an improvement in key pro-regenerative events, namely, the increased expression of neurofilament and growth-associated protein GAP-43 in the injured nerves. Moreover, the targeted nanoparticle treatment was correlated with a significantly higher density of myelinated axons in the distal stump of injured nerves, as well as with preservation of unmyelinated axon density as compared with controls and a protective role in injury-denervated muscles, preventing them from denervation. These results highlight the potential of TMCSH-HC nanoparticles as non-viral gene carriers to deliver therapeutic genes into the peripheral neurons and thus, pave the way for their use as an effective therapeutic intervention for peripheral neuropathies.



http://ift.tt/2ibqHPt

Targeted delivery of in situ PCR-amplified Sleeping Beauty transposon genes to cancer cells with lipid-based nanoparticle-like protocells

Publication date: March 2017
Source:Biomaterials, Volume 121
Author(s): Kun Ma, Duo Fu, Dongli Yu, Changhao Cui, Li Wang, Zhaoming Guo, Chuanbin Mao
A Sleeping Beauty (SB) transposon system is made of a transposon plasmid (containing gene encoding a desired functional or therapeutic protein) and a transposase plasmid (encoding an enzyme capable of cutting and pasting the gene into the host cell genome). It is a kind of natural, nonviral gene delivery vehicle, which can achieve efficient genomic insertion, providing long-term transgenic expression. However, before the SB transposon system could play a role in promoting gene expression, it has to be delivered efficiently first across cell membrane and then into cell nuclei. Towards this end, we used a nanoparticle-like lipid-based protocell, a closed bilayer of the neutral lipids with the DNA encapsulated inside, to deliver the SB transposon system to cancer cells. The SB transposon system was amplified in situ inside the protocells by a polymerase chain reaction (PCR) process, realizing more efficient loading and delivery of the target gene. To reach a high transfection efficiency, we introduced two targeting moieties, folic acid (FA) as a cancer cell-targeting motif and Dexamethasone (DEX) as a nuclear localization signaling molecule, into the protocells. As a result, the FA enabled the modified targeting protocells to deliver the DNA into the cancer cells with an increased efficiency and the DEX promoted the DNA to translocate to cell nuclei, eventually leading to the increased chromosome insertion efficiency of the SB transposon. In vivo study strongly suggested that the transfection efficiency of FA-modified protocells in the tumor tissue was much higher than that in other tissues, which was consistent with the in vitro results. Our studies implied that with the targeting ligand modification, the protocells could be utilized as an efficient targeting gene carrier. Since the protocells were made of neutral lipids without cationic charges, the cytotoxicity of protocells was significantly lower than that of traditional cationic gene carriers such as cationic liposomes and polyethylenimine, enabling the protocells to be employed in a wider dosage range in gene therapy. Our work shows that the protocells are a promising gene carrier for future clinical applications.



http://ift.tt/2idEfgx

Blood-brain barrier dysfunction induced by silica NPs in vitro and in vivo: Involvement of oxidative stress and Rho-kinase/JNK signaling pathways

Publication date: March 2017
Source:Biomaterials, Volume 121
Author(s): Xin Liu, Baiyan Sui, Jiao Sun
Silica nanoparticles (SiO2-NPs) has been extensively exploited in biomedical fields and mostly designed to enter the circulatory system, however, few studies focused on the potential adverse effects of SiO2-NPs exposure on the blood-brain barrier (BBB) that serves as a critical barrier between the central nervous system (CNS) and the peripheral circulation. This study attempts to provide an understanding of whether and how SiO2-NPs disrupts the BBB in vitro and in vivo. Through a human BBB model, we found that SiO2-NPs could induce tight junction loss and cytoskeleton arrangement, and increase inflammatory response and the release of vascular endothelial growth factor (VEGF) of brain microvessel endothelial cells (BMECs), which further activates astrocytes to amplify the generation of VEGF and increase the aquaporin-4 expression, and thus causing BBB disruption through a complex immunoregulatory loop between BMECs and astrocytes under SiO2-NPs exposure. Additionally, our data show that inhibition of reactive oxygen species (ROS) and Rho-kinase (ROCK) could effectively protect the SiO2-NPs-induced BBB dysfunction. In vivo studies further confirmed that SiO2-NPs could cause the BBB paracellular opening, oxidative stress and astrocyte activation in brains of Sprague–Dawley (SD) rats. These findings demonstrate that SiO2-NPs could disturb BBB structure and function and induce BBB inflammation, and suggest that these effects may occur through ROS and ROCK-mediated pathways, which not only improve neurotoxicity evaluation for SiO2-NPs but also provide useful information in development of SiO2-NPs in neuro-therapeutics and nanodiagnostics.



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In vitro evaluation of biodegradable lignin-based nanoparticles for drug delivery and enhanced antiproliferation effect in cancer cells

Publication date: March 2017
Source:Biomaterials, Volume 121
Author(s): Patrícia Figueiredo, Kalle Lintinen, Alexandros Kiriazis, Ville Hynninen, Zehua Liu, Tomás Bauleth-Ramos, Antti Rahikkala, Alexandra Correia, Tomáš Kohout, Bruno Sarmento, Jari Yli-Kauhaluoma, Jouni Hirvonen, Olli Ikkala, Mauri A. Kostiainen, Hélder A. Santos
Currently, nanosystems have been developed and applied as promising vehicles for different biomedical applications. We have developed three lignin nanoparticles (LNPs): pure lignin nanoparticles (pLNPs), iron(III)-complexed lignin nanoparticles (Fe-LNPs), and Fe3O4-infused lignin nanoparticles (Fe3O4-LNPs) with round shape, narrow size distribution, reduced polydispersity and good stability at pH 7.4. The LNPs showed low cytotoxicity in all the tested cell lines and hemolytic rates below 12% after 12 h of incubation. Additionally, they induced hydrogen peroxide production in a small extent and time-dependent manner, and the interaction with the cells increased over time, exhibiting a dose-dependent cell uptake. Concerning the drug loading, pLNPs showed the capacity to efficiently load poorly water-soluble drugs and other cytotoxic agents, e.g. sorafenib and benzazulene (BZL), and improve their release profiles at pH 5.5 and 7.4 in a sustained manner. Furthermore, the BZL-pLNPs presented an enhanced antiproliferation effect in different cells compared to the pure BZL and showed a maximal inhibitory concentration ranging from 0.64 to 12.4 μM after 24 h incubation. Overall, LNPs are promising candidates for drug delivery applications, and the superparamagnetic behavior of Fe3O4-LNPs makes them promising for cancer therapy and diagnosis, such as magnetic targeting and magnetic resonance imaging.



http://ift.tt/2idKd17

Correlation between Antigenicity and Variability in the vls Antigenic Variation System of Borrelia burgdorferi

Publication date: Available online 10 January 2017
Source:Microbes and Infection
Author(s): Wei Zhou, Dustin Brisson
Many parasites have evolved antigenic variation systems that alter surface proteins in order to evade recognition by presently expressed antibodies and subsequent death. Although the amino acid positions in antigens to which antibodies most commonly target are expected to be the most variable, this assumption has not been investigated. Using the vls antigenic variation system of Borrelia burgdorferi as a model, we first investigated this assumption computationally and then developed a sensitive immunoassay to experimentally validate the computational results. There was a strong correlation between variability at an amino acid position and each of the computational metrics associated with antibody reactivity. However, empirical measures of antibody reactivity were not consistently greater at the variable amino acid positions than at the invariant amino acid positions. The inconsistent experimental support for this hypothesis suggests that the biological effect of variability at an amino acid position is obfuscated by other factors.



http://ift.tt/2jgZP29

An observational study of phagocytes and Klebsiella pneumoniae relationships: different behaviors

Publication date: Available online 10 January 2017
Source:Microbes and Infection
Author(s): Elodie Maisonneuve, Estelle Cateau, Marion Delouche, Nathalie Quellard, Marie-Helene Rodier
Klebsiella pneumoniae is a bacterium that can be in relation with free living amoebae like Acanthamoeba castellanii in natural environments such as soil and water. This pathogen, which is responsible for community-acquired pneumonia and for nosocomial infections, also has interactions with host defence mechanisms like macrophages. As it has been shown that A. castellanii shares some traits with macrophages, in particular the ability to phagocyte bacteria, we have studied the uptake and the fate of the bacteria after contact with the two phagocytic cells. In our conditions, K. pneumoniae growth was increased in coculture in presence of A. castellanii or Thp-1 macrophagic cells and bacterial development was also increased by A. castellanii supernatant. In addition, we showed that the presence of the bacteria had a negative effect on the macrophages whereas it does not affect amoeba viability. Using gentamicin, which kills bacteria outside cells, we showed that only macrophages were able to internalize K. pneumoniae. This result was confirmed by electron microscopy. We have consequently reported some differences in bacterial uptake and internalization between a free living amoeba and macrophagic cells, highlighting the fact that results obtained with this amoebal model should not be extrapolated to the relationships between K. pneumoniae and macrophages.



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The impact of ISGylation during Mycobacterium tuberculosis infection in mice

Publication date: Available online 10 January 2017
Source:Microbes and Infection
Author(s): Jacqueline M. Kimmey, Jessica A. Campbell, Leslie A. Weiss, Kristen J. Monte, Deborah J. Lenschow, Christina L. Stallings
Mycobacterium tuberculosis infection results in 1.5 million deaths annually. Type I interferon (IFN) signaling through its receptor IFNAR correlates with increased severity of disease, although how this increases susceptibility to M. tuberculosis remains uncertain. ISG15 is one of the most highly induced interferon stimulated genes (ISGs) during M. tuberculosis infection. ISG15 functions by conjugation to target proteins (ISGylation), by noncovalent association with intracellular proteins, and by release from the cell. Recent studies indicated that ISG15 can function via conjugation-independent mechanisms to suppress the type I IFN response. These data raised the question of whether ISG15 may have diverse and sometimes opposing functions during M. tuberculosis infection. To address this, we analyzed ISGylation during M. tuberculosis infection and show that ISGylated proteins accumulate following infection in an IFNAR-dependent manner. Type I IFN and ISG15 both play transient roles in promoting bacterial replication. However, as the disease progresses, ISGylation deviates from the overall effect of type I IFN and, ultimately, mice deficient in ISGylation are significantly more susceptible than IFNAR mice. Our data demonstrate that ISGs can both protect against and promote disease and are the first to report a role for ISGylation during M. tuberculosis infection.



http://ift.tt/2jh3RYd

Audiologic and radiologic findings in cochlear hypoplasia

Publication date: Available online 10 January 2017
Source:Auris Nasus Larynx
Author(s): Betul Cicek Cinar, Merve Ozbal Batuk, Emel Tahir, Gonca Sennaroglu, Levent Sennaroglu
ObjectiveThe aim of the current study is to evaluate audiologic and radiologic findings of cochlear hypoplasia which is a subgroup of inner ear malformations.MethodsThis study was a prospective clinical study and based on voluntary participation from cases with cochlear hypoplasia diagnosis. The study was conducted at Hacettepe University, Department of Otolaryngology, Head and Neck Surgery and Department of Audiology. Subjects were selected from an inner ear malformations database. Inclusion criteria were having cochlear hypoplasia for at least one ear. There were 66 subjects with an age range of 12 months and 60 years 5 months. For each subject, pure tone audiometry and tympanometry were applied according to chronological and cognitive age. And also, auditory brainstem response test was applied to when it is need. Subjects' radiologic results were reevaluated to confirm cochlear hypoplasia, cochlear nerve and cochlear aperture.ResultsCochlear hypoplasia types were statistically significantly different in terms of HL degree. This difference was caused by cochlear hypoplasia type IV group being was statistically different from the other three groups. Like with degree of HL, cochlear hypoplasia groups were statistically different from other three groups in terms of type of hearing loss. Cochlear aperture and cochlear nerve status showed variation according to cochlear hypoplasia type but these differences were not statistically approved.ConclusionsIn the current study, incidence of cochlear hypoplasia was 23.5% in all inner ear malformation. With this study, it was seen that subtypes of cochlear hypoplasia showed variability in terms of degree and type of hearing loss and also cochlear aperture and cochlear nerve status. Especially cochlear hypoplasia type IV differs from other three cochlear hypoplasia types.



http://ift.tt/2jBCpb8

Synthesis and characterization of gold nanostructured Chorin e6 for Photodynamic Therapy

Publication date: Available online 10 January 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): L. Vieira, M.L. Castilho, I. Ferreira, J. Ferreira-Strixino, K.C. Hewitt, L. Raniero
Photodynamic therapy is an alternative treatment for cancer based on cellular uptake of a photosensitizer, illuminated with an appropriate wavelength in the presence of oxygen. A cascade of reactions generates reactive oxygen species leading to cell death. Using carbodiimide chemistry, chlorin e6 (Ce6) was covalently bonded to thiourea, and (via the sulphur end group) to gold nanoparticles (AuNPs), forming the Ce6-AuNP complex. Ce6 absorbs in the range 650–680nm, where the coefficient of biological tissue absorption is low (part of the therapeutic window), which is ideal for biological application. Transmission Electron Microscopy, UV–vis spectroscopy, Fourier transform Infrared Spectroscopy and Zeta potential measurements were completed to characterize the Ce6-AuNP complex. The bare AuNPs have an average diameter of 18±4nm. A line of human breast carcinoma cells (MDA-MB-468) were used to determine whether Ce6 functionalization to AuNPs potentiate its activity. Trypan blue assays were used to assess cell viability. In the absence of light, Ce6 either alone or bounded to AuNPs was not cytotoxic. When irradiated at 660nm, the cytotoxicity of Ce6-AuNP was higher than Ce6 alone for MDA-MB-468 cells using 4h incubation. AuNPs without Ce6 showed no cytotoxic.



http://ift.tt/2ielczo

Thyroid hormones induce browning of white fat

The canonical view about the effect of thyroid hormones (THs) on thermogenesis assumes that the hypothalamus acts merely as a modulator of the sympathetic outflow on brown adipose tissue (BAT). Recent data have challenged that vision by demonstrating that THs act on the ventromedial nucleus of the hypothalamus (VMH) to inhibit AMP-activated protein kinase (AMPK), which regulates the thermogenic program in BAT, leading to increased thermogenesis and weight loss. Current data have shown that in addition to activation of brown fat, the browning of white adipose tissue (WAT) might also be an important thermogenic mechanism. However, the possible central effects of THs on the browning of white fat remain unclear. Here, we show that 3,3',5,5' tetraiodothyroxyne (T₄)-induced hyperthyroidism promotes a marked browning of WAT. Of note, central or VMH-specific administration of 3,3',5-triiodothyronine (T₃) recapitulates that effect. The specific genetic activation of hypothalamic AMPK in the VMH reversed the central effect of T₃ on browning. Finally, we also showed that the expression of browning genes in human WAT correlates with serum T₄. Overall, these data indicate that THs induce browning of WAT and that this mechanism is mediated via the central effects of THs on energy balance.

http://ift.tt/2jBGj3I

Coreference and Antecedent Representation Across Languages.

Author: Lago, Sol; Sloggett, Shayne; Schlueter, Zoe; Chow, Wing Yee; Williams, Alexander; Lau, Ellen; Phillips, Colin

DOI: 10.1037/xlm0000343

Publication Date: POST AUTHOR CORRECTIONS, 9 January 2017

http://ift.tt/2ih8IKy

Cognitive Effort Is Modulated Outside of the Explicit Awareness of Conflict Frequency: Evidence From Pupillometry.

Author: Diede, Nathaniel T.; Bugg, Julie M.

DOI: 10.1037/xlm0000349

Publication Date: POST AUTHOR CORRECTIONS, 9 January 2017

http://ift.tt/2ih3DCa

Using Perspective to Resolve Reference: The Impact of Cognitive Load and Motivation.

Author: Cane, James E.; Ferguson, Heather J.; Apperly, Ian A.

DOI: 10.1037/xlm0000345

Publication Date: POST AUTHOR CORRECTIONS, 9 January 2017

http://ift.tt/2jgW4cV

Basic Composition and Enriched Integration in Idiom Processing: An EEG Study.

Author: Canal, Paolo; Pesciarelli, Francesca; Vespignani, Francesco; Molinaro, Nicola; Cacciari, Cristina

DOI: 10.1037/xlm0000351

Publication Date: POST AUTHOR CORRECTIONS, 9 January 2017

http://ift.tt/2jgZso6

Our Moral Choices Are Foreign to Us.

Author: Corey, Joanna D.; Hayakawa, Sayuri; Foucart, Alice; Aparici, Melina; Botella, Juan; Costa, Albert; Keysar, Boaz

DOI: 10.1037/xlm0000356

Publication Date: POST AUTHOR CORRECTIONS, 9 January 2017

http://ift.tt/2ih4ItG

IgE cross-linking impairs monocyte antiviral responses and inhibits influenza-driven Th1 differentiation

Capsule Summary: IgE-mediated allergic activation impairs the virus-induced Th1 lymphocyte priming capacity of human monocytes in response to influenza exposure. These findings represent one potential mechanism contributing to the link between viral infections and allergic disease.

http://ift.tt/2jgS3Ft

Does size really matter- relationship of particle size to lung deposition and exhaled fraction

Capsule summary: We demonstrate that extra-fine particles are not associated with an appreciably higher exhaled fraction, hence explaining their efficacy profile in asthma.

http://ift.tt/2j3xTkE

Autoimmune lymphoproliferative syndrome caused by homozygous FAS mutations with normal or residual protein expression

Capsule summary: The identification of homozygous FAS mutations with normal or residual protein expression expands the spectrum of autoimmune lymphoproliferative syndrome types and should prompt clinicians to search for such patients particularly in highly endogamous populations.

http://ift.tt/2jgBg5k

Identification of drug- and drug-metabolite immune responses originating from both naïve and memory T-cells

Summary: Both naïve and memory T-cells from drug-naive donors can be stimulated by parent drug and drug haptens. Thus, drug-derived antigens can stimulate naïve T-cells alongside pre-existing memory T-cells through proposed heterologous immunity with an as yet undetermined peptide antigen.

http://ift.tt/2j3BFe0

The perfusion code of DIEP and ms-TRAM flaps is a hard nut to crack

We read with interest the article by Ludolph et al. entitled "Cracking the perfusion code?: Laser-assisted Indocyanine Green angiography and combined laser Doppler spectrophotometry for intraoperative evaluation of tissue perfusion in autologous breast reconstruction with DIEP or ms-TRAM flaps".1 We completely agree with the authors that intraoperative evaluation of flap perfusion can still be challenging. Such is especially true in those cases where flaps are composed of several angiosomes as is usually the case with the DIEP and ms-TRAM flaps.

http://ift.tt/2ibhifu

Synthesis and characterization of biodegradable multiblock poly(carbonate-co-esters) containing biobased monomer

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Cai Xiaodong, Yang Xiangui, Wang Gongying
Multiblock poly(carbonate-co-esters) (PBC-PBSe) containing poly(butylene carbonates) (PBC) and poly(butylene sebacate) (PBSe) were synthesized successfully via chain-extension of dihydroxyl terminated PBC (PBC-OH) and PBSe (PBSe-OH) using 1,6-hexmethylene diisocyanate (HDI) as chain extender. The chemical structures, molecular weights, crystallization behaviors, thermal, degradation as well as mechanical properties of the copolyesters were characterized by Proton nuclear magnetic resonance spectroscopy (¹H NMR), Fourier transform infrared spectroscopy (FT-IR), Gel permeation chromatography (GPC), Differential scanning calorimetry (DSC), Thermogravimetry analysis (TGA), hydrolytic degradation and mechanical testing, respectively. The results indicated that the introduction of PBSe segment not only significantly enhanced the crystallization rate of PBC, but also displayed the same crystallization mechanism within the investigated crystallization temperature range despite of the variation of the PBSe segment content. Furthermore, the thermal stability and hydrolytic degradation rate of PBC-PBSe multiblock copolymers increases with increasing PBSe content. The mechanical properties of copolymers can be adjusted by changing the feed composition.

Graphical abstract

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Kinetics of early stages of resorcinol-formaldehyde polymerization investigated by solution-phase nuclear magnetic resonance spectroscopy

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Katarzyna Z. Gaca, John A. Parkinson, Jan Sefcik
Resorcinol and formaldehyde reactions were quantitatively monitored by means of ¹H and ¹³C NMR spectroscopy at room temperature (293 K) before heat treatment leading to formation of organic gels. We found that resorcinol substitution with formaldehyde starts with an initial surprisingly rapid step followed by a more gradual depletion of the reactants. Substituted species with both monomeric and dimeric hydroxymethyl groups were observed immediately after mixing of the reagents with the proportion of formaldehyde-based solution species consumed between 30 and 50%. Substituted resorcinol species can be all accounted for by solution-phase NMR at ambient conditions before they form nanoscale clusters upon heating. It can therefore be expected that the final properties of resorcinol-formaldehyde gels depend not only on the composition of reaction mixtures and duration of the high temperature treatment but also on the manner and period of reagent mixing (a hitherto overlooked synthesis step), as different amounts of alternatively substituted resorcinol can be produced before heat treatment commences.

Graphical abstract

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Synthesis of emulsion-templated macroporous materials via Diels-Alder polymerization

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Chenchen Xiao, Yun Zhu, Jianding Chen, Shengmiao Zhang
Emulsion-templated macroporous materials, known in the literature for many years as polyHIPEs, have found an increasing number of applications due to their well-defined structures. However, most of the emulsion-templated materials are synthesized using conventional radical polymerization, and most of the radical polymerization are thermally initiated. Expanding the polymerization mechanisms available for emulsion-templated material synthesis is still highly desired. In this work, macroporous polymers were firstly synthesized by Diels-Alder reaction of furan derivatives and bismaleimide within the continuous phase of particle-stabilized emulsions. These polymers have a well-defined controllable porous structure and good self-healing performance.

Graphical abstract

http://ift.tt/2j3JDUu

Facile fabrication of core-shell polyelectrolyte complexes nanofibers based on electric field induced phase separation

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Haoqin Ma, Guangkai Chen, Jingnan Zhang, Yong Liu, Jun Nie, Guiping Ma
The core-shell polyelectrolyte complexes chitosan (CS)/hyaluronic acid (HA) nanofibers could be produced from electric field inducing phase separation during the progress of electrospinning. The morphology of core-shell nanofibers was supported using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The presence of CS on the shell of the nanofibers was also verified by X-ray photoelectron spectroscopy (XPS) analysis as further evidence of core-shell formation. In the electrospinning process, the protonated CS molecules migrated in the direction of the electric field, whereas the ionized HA molecules migrated in the opposite direction. Methylthiazolydiphenyl-tetrazolium bromide (MTT) assay was employed to investigate the toxic and cytocompatibility with the possible application for tissue engineering scaffolds. The drug release from core–shell nanofiber in vitro was investigated by UV spectrophotometry. The release profiles for core–shell nanofibers showed more controlled and sustained release. while fibroblasts cells could still adhere to and proliferate on the drug-loaded core–shell nanofiber membranes. The results implied that core-shell polyelectrolyte complexes CS/HA nanofibers encapsulating drugs have great potential in tissue engineering scaffolds.

Graphical abstract

http://ift.tt/2jsPlMx

Coil-helix-globule transition for self-attractive semiflexible ring chains

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Zhiyong Yang, Zheyu Deng, Linxi Zhang
An off-lattice dynamics Monte Carlo method is used to study the conformations of self-attractive semiflexible ring chains. The conformations depend mainly on the bending energy b and the self-attractive interaction ε of ring chains, and perfect helical structures are found in self-attractive semiflexible ring chains with the moderate attractive interaction ε. Some monomers of the semiflexible ring chains wrap around the linearly aligned monomers and the size of helix is independent of chain length of ring chains. Coil-helix-globule transition occurs when the self-attractive interaction increases within semiflexibe ring chains, and the phase transition is attributed to the competition among the configurational entropy, the bending energy, and the self-attractive interaction. This study can help us understand the effects of topological constraints on the conformations and dynamical behaviors of polymer chains, and the importance of chain stiffness in biological systems and in the dynamics of DNA and protein folding.

Graphical abstract

http://ift.tt/2jsQL9C

Novel shape memory behaviour in IPDI based polyurethanes: Influence of nanoparticle

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Satyam Srivastava, Arpan Biswas, Sudipta Senapati, Biswajit Ray, Dipak Rana, Vinod K. Aswal, Pralay Maiti
A diverse nanostructure, key to property alteration, has been observed by the insertion of two dimensional nanoparticles through in-situ polymerization. Self-assembly at the molecular level has been revealed starting from nanoscale to observable microscale in thermoplastic polyurethane using alicyclic diisocyanate and how the self-assembly behaviour changes in presence of nanoparticle. Varying dispersion of nanoparticles observed using two different fillers has been explained from the interactions point of view through spectroscopic techniques. Thermal stability and unique crystallization behaviour have been reported in presence of nanoparticles. Better dispersion of nanofillers within the matrix offers greater number of nucleating site which enhances the ordering of the polymer chains, also supported by the semi-empirical calculation. The effect of modulated nanostructure and self-assembly augmented the shape memory behaviour in polyurethanes having alicyclic diisocyanate. Enhanced shape recovery has been observed in presence of organically modified clay as opposed to layered double hydroxide. The reason for this improved shape memory behaviour in nanohybrid is explained from the exclusive crystallization of the soft segment domain leading to a proposed model for shape recovery. Finally, the recovery of different shapes (coil, spinal and straight strip) at physiological temperature (37 °C) has been demonstrated, added advantage of these materials to be used in the biomedical applications.

Graphical abstract

http://ift.tt/2jsN7fX

One-step synthesis of PHEMA hydrogel films capable of generating highly ordered wrinkling patterns

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Jianjun Gu, Xiaoyun Li, Hancheng Ma, Ying Guan, Yongjun Zhang
Poly(2-hydroxyethyl methacrylate) (PHEMA) films with gradient crosslinking density are the only hydrogel films capable of generating regular wrinkling patterns upon swelling, however, they were synthesized via a complicated two-stage photopolymerization. In an effort to develop a simple synthesis method, we found that one-step UV-curing of HEMA liquid always results in films with corrugated surface, which is a common issue when curing liquid prepolymers. We further found that the introduction of a physical network in the prepolymer solution could prevent the surface from corrugating during UV curing. For this purpose, linear PHEMA was added into the prepolymer solutions, and PHEMA films with a smooth surface were successfully synthesized by a simple one-step UV curing. The resulting films generate various swelling-induced wrinkling patterns, including random worms, peanuts and long-range ordered hexagons, depending on the contents of crosslinker and linear PHEMA in the prepolymer solution. Particularly, large area, highly ordered, honeycomb-like wrinkling patterns were obtained from films with proper content of crosslinker and linear PHEMA. These regular patterns are expected to find applications such as the fabrication of uniform multicellular spheroids.

Graphical abstract

http://ift.tt/2jsMDXm

Preparation of stable poly(methacrylic acid)-b-polystyrene emulsion by emulsifier-free emulsion iodine transfer polymerization (emulsion ITP) with self-assembly nucleation

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): S. Sue-eng, T. Boonchuwong, P. Chaiyasat, M. Okubo, A. Chaiyasat
Emulsifier-free emulsion iodine transfer polymerization (emulsion ITP) of styrene with self-assembly nucleation was successfully carried out with some living features for the first time as follows. Firstly, poly(methacrylic acid) (PMAA; degree of polymerization, 37)-iodide (PMAA37-I) as a macro chain transfer agent was synthesized by solution reversible chain transfer catalyzed polymerization (solution RTCP) with 2,2′-azobis(4-methoxy-2,4-dimethylvaleronitrile) as an initiator, iodoform as a chain transfer agent and germanium iodide as a catalyst in dioxane at 40 °C. A dioxane solution of PMAA37-I and styrene were added stepwisely under stirring into an aqueous solution (pH∼9), and then emulsion ITP was initiated by adding 4,4′-azobis(4-cyanopentanoic acid) at 60 °C with stirring at 500 rpm. Stable polystyrene emulsion was obtained without coagulation. At 100% conversion, the number-average diameter was 223 nm. Number-average molecular weight (Mn) increased linearly with conversion, which were well closed to theoretical Mn and molecular weight distribution at 100% conversion was comparatively narrow (Mw/Mn∼2.1).

Graphical abstract

http://ift.tt/2jsK9ID

In vitro oral bioaccessibility and total content of Cu, Fe, Mn and Zn from transgenic (through cp4 EPSPS gene) and nontransgenic precursor/successor soybean seeds

Publication date: 15 June 2017
Source:Food Chemistry, Volume 225
Author(s): Mónica A. Herrera-Agudelo, Manuel Miró, Marco A.Z. Arruda
In this paper, Cu, Fe, Mn and Zn contents in transgenic (T – MSOY7122RR) and non-transgenic (NT – MSOY8200) soybean seeds, sown at summer and winter cultivation periods are investigated using four microwave decomposition methods. Student's t tests demonstrate significant differences (p=0.05; n=4), for Cu, Mn and Zn (namely, 8, 9 and 26% higher concentrations in T compared to NT seeds, respectively). Through principal component analysis, precursor and successor soybean seeds are identified. Cu is demonstrated to play an important role in the differentiation of the cultivars, whereas Fe and Zn are of particular relevance in the classification of seeds cultivated in winter against those in summer. Using in vitro extraction based on the Unified Bioaccessibility Method, the bioaccessibility of the above nutrients is proven to differ in both the gastric and gastrointestinal phases on the basis of the transgenesis and the cultivation periods.



http://ift.tt/2iDyhDg

Superplasticity of clad aluminium alloy

Publication date: May 2017
Source:Journal of Materials Processing Technology, Volume 243
Author(s): A.V. Mikhaylovskaya, A.G. Mochugovskiy, A.D. Kotov, O.A. Yakovtseva, M.V. Gorshenkov, V.K. Portnoy
Different Al-based alloys were evaluated as materials for cladding on a high-strength Al-Zn-Mg-Cu-Ni-Zr alloy with high-strain rate superplasticity. Clad sheets were fabricated by hot-roll bonding. Superplastic behaviour, mechanical properties at room temperature and corrosion properties of clad sheets were studied. The microstructure analysis and tensile results revealed that bonding was acceptable in the samples with cladding materials. The research revealed that the Al-Zn-Ca alloy provided good corrosion protection, superplasticity and a low decrease in the mechanical properties of cladded sheets.

Graphical abstract

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Safety and tolerability of pasireotide long-acting release in acromegaly—results from the acromegaly, open-label, multicenter, safety monitoring program for treating patients who have a need to receive medical therapy (ACCESS) study

Abstract

Purpose

Pasireotide long-acting release is a somatostatin analog that is indicated for treatment of patients with acromegaly. This analysis documents the safety of pasireotide long-acting release in patients with acromegaly enrolled in the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734).

Methods

ACCESS is an open-label, multicenter, single-arm, expanded-treatment protocol designed to provide patients access to pasireotide long-acting release pending regulatory approval. Patients received pasireotide long-acting release 40 mg administered intramuscularly every 28 days. The primary outcome was the proportion of patients having a treatment-emergent grade ≥3 or serious adverse event. Efficacy data were not collected.

Results

Forty-four adult patients with active acromegaly were enrolled in the study for an average of 37.6 weeks (range, 4–70 weeks). Twenty-five grade ≥3 treatment-emergent adverse events were reported in 11 patients (25.0 %), 3 of whom (27.3 %) experienced grade ≥3 hyperglycemia. In patients treated with pasireotide long-acting release for ≥3 months (n = 42), mean glycated hemoglobin and fasting plasma glucose levels increased significantly from 5.9 % and 100.4 mg/dL at baseline to 6.8 % and 135.9 mg/dL at 3 months, respectively. Ten patients (22.7 %) were treated with pasireotide long-acting release for ≥15 months, after which mean glycated hemoglobin and fasting plasma glucose levels were 6.3 % and 123 mg/dL, respectively. Twenty-one patients (48 %) initiated antidiabetic medication.

Conclusions

Grade ≥3 adverse events (primary outcome) were reported in 25.0 % of acromegaly patients treated with pasireotide long-acting release in a clinical setting. Hyperglycemia-related adverse events were reported in 45.5 % of patients, but were typically manageable, supporting the role of pasireotide long-acting release as a safe treatment option for acromegaly patients.

http://ift.tt/2j5WAgP

Vitamin D and primary hyperparathyroidism: more insights into a complex relationship

http://ift.tt/2jsJW8h

Erratum to: Prospective, long-term study of the effect of cabergoline on valvular status in patients with prolactinoma and idiopathic hyperprolactinemia

http://ift.tt/2j5ONzn

VideoEndocrinology™ High-Impact Videos

FREE ACCESS through January 24, 2017.

Thyroidectomy with Wu Gaosong's Procedure
Gaosong Wu, Deguang Kong

Transoral Endoscopic Thyroidectomy Vestibular Approach
Angkoon Anuwong, Thanyawat Sasanakietkul, Pornpeera Jitpratoom

Transoral Robotic Thyroidectomy
Jeremy D. Richmon, Ralph P. Tufano, Jon Russell, Andrew Day, Hamad M. Chaudhary, Salem I. Noureldine

Novel Experience with Neuromonitoring in Robotic Thyroidectomy Using a Gasless Transaxillary Approach
Eun Jeong Ban, Changro Lee, Seul Gi Lee, Cho Rok Lee, Min Jhi Kim, Jung Bum Choi, Taehyung Kim, Sang Wook Kang, Jandee Lee, Jong Ju Jeong, Kee-Hyun Nam, Woong Youn Chung

A New Method for Direct Evaluation of Incisional Swelling After Thyroidectomy
Jenny Y. Yoo, Kelly L. McCoy, Linwah Yip, Michael T. Stang, Sally E. Carty

Indocyanine Green Fluorescence to Enhance Visual Contrast During Robotic Transaxillary Total Thyroidectomy
Pinar Yazici, Ryaz Chagpar, Sara Sound, Alexis Okoh, Eren Berber

Identification of the External Branch of the Superior Laryngeal Nerve During Thyroidectomy
Jonathan M. Bernstein, Jeremy L. Freeman

Robotic Thyroidectomy: Facelift Approach
Jeremy Richmon, Jason Prescott, Ralph Tufano, Martha Zeiger, Alan Dackiw,Heather Starmer

The post VideoEndocrinology™ High-Impact Videos appeared first on American Thyroid Association.

http://ift.tt/2jstC7f

VideoEndocrinology™ High-Impact Videos

FREE ACCESS through January 24, 2017.

Thyroidectomy with Wu Gaosong's Procedure
Gaosong Wu, Deguang Kong

Transoral Endoscopic Thyroidectomy Vestibular Approach
Angkoon Anuwong, Thanyawat Sasanakietkul, Pornpeera Jitpratoom

Transoral Robotic Thyroidectomy
Jeremy D. Richmon, Ralph P. Tufano, Jon Russell, Andrew Day, Hamad M. Chaudhary, Salem I. Noureldine

Novel Experience with Neuromonitoring in Robotic Thyroidectomy Using a Gasless Transaxillary Approach
Eun Jeong Ban, Changro Lee, Seul Gi Lee, Cho Rok Lee, Min Jhi Kim, Jung Bum Choi, Taehyung Kim, Sang Wook Kang, Jandee Lee, Jong Ju Jeong, Kee-Hyun Nam, Woong Youn Chung

A New Method for Direct Evaluation of Incisional Swelling After Thyroidectomy
Jenny Y. Yoo, Kelly L. McCoy, Linwah Yip, Michael T. Stang, Sally E. Carty

Indocyanine Green Fluorescence to Enhance Visual Contrast During Robotic Transaxillary Total Thyroidectomy
Pinar Yazici, Ryaz Chagpar, Sara Sound, Alexis Okoh, Eren Berber

Identification of the External Branch of the Superior Laryngeal Nerve During Thyroidectomy
Jonathan M. Bernstein, Jeremy L. Freeman

Robotic Thyroidectomy: Facelift Approach
Jeremy Richmon, Jason Prescott, Ralph Tufano, Martha Zeiger, Alan Dackiw,Heather Starmer

The post VideoEndocrinology™ High-Impact Videos appeared first on American Thyroid Association.

http://ift.tt/2jstC7f

Factors influencing and modifying the decision to pursue genetic testing for skin cancer risk

Across cancers, the decision to pursue genetic testing is influenced more by subjective than objective factors. However, skin cancer, which is more prevalent, visual, and multifactorial than many other malignancies, may offer different motivations for pursuing such testing.

http://ift.tt/2iDpYr4

Secukinumab sustains early patient-reported outcome benefits through 1 year: Results from 2 phase III randomized placebo-controlled clinical trials comparing secukinumab with etanercept

Psoriasis is a chronic condition with negative impact on patients' quality of life that most often requires lifelong effective and safe treatment.

http://ift.tt/2idThzP

Hookah tobacco smoking in a large urban sample of adult cigarette smokers: Links with alcohol and poly-tobacco use

Publication date: May 2017
Source:Addictive Behaviors, Volume 68
Author(s): Amy M. Cohn, Sarah J. Ehlke, Caroline O. Cobb, Eric K. Soule
Hookah tobacco smoking (HTS) has been increasing, particularly among young adults and has similar health effects compared to cigarette smoking. The link between HTS and poly-tobacco use is well documented, but fewer show an association between HTS and alcohol use. It is essential to identify factors that increase the risk for or addictiveness and consequences of HTS, given its growing prevalence. This study examined whether the association between HTS and poly-tobacco use differed as a function of age and alcohol consumption within in a sample of 1223 adult cigarette smokers. Approximately 20% of participants reported HTS. Compared to non-users, hookah users were more likely to be male, highly educated, and to report drug and alcohol use, binge drinking, and poly-tobacco use but were less likely to be heavy smokers (≥10 cigarettes per day). Regression analyses predicting number of tobacco products used (excluding cigarettes and HTS) indicated a three-way interaction of HTS, frequency of alcohol use, and age such that the association between HTS and number of tobacco products used was strongest for younger respondents who consumed alcohol more frequently. As observed in previous studies, alcohol is an important risk factor in the relationship between HTS and poly-tobacco use, particularly among younger cigarette smokers. The links between alcohol, HTS, and poly-tobacco use should be considered when developing HTS education and prevention materials directed toward younger cigarette smokers. Findings provide information relevant to FDA's interest in the addiction potential of HTS and its link to poly-tobacco use.



http://ift.tt/2jsGlqG

Bayesian MRI denoising in complex domain

Publication date: May 2017
Source:Magnetic Resonance Imaging, Volume 38
Author(s): Fabio Baselice, Giampaolo Ferraioli, Vito Pascazio, Antonietta Sorriso
In recent years, several efforts have been done for producing Magnetic Resonance Image scanner with higher magnetic field strength mainly for increasing the Signal to Noise Ratio and the Contrast to Noise Ratio of the acquired images. However, denoising methodologies still play an important role for achieving images neatness. Several denoising algorithms have been presented in literature. Some of them exploit the statistical characteristics of the involved noise, some others project the image in a transformed domain, some others look for geometrical properties of the image. However, the common denominator consists in working in the amplitude domain, i.e. on the gray scale, real valued image. Within this manuscript we propose the idea of performing the noise filtering in the complex domain, i.e. on the real and on the imaginary parts of the acquired images. The advantage of the proposed methodology is that the statistical model of the involved signals is greatly simplified and no approximations are required, together with the full exploitation of the whole acquired signal. More in detail, a Maximum A Posteriori estimator developed for the handling complex data, which adopts Markov Random Fields for modeling the images, is proposed. First results and comparison with other widely adopted denoising filters confirm the validity of the method.



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The Acoustic Breathiness Index (ABI): A Multivariate Acoustic Model for Breathiness

The evaluation of voice quality is a major component of voice assessment. The aim of the present study was to develop a new multivariate acoustic model for the evaluation of breathiness.

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Conversational Entrainment of Vocal Fry in Young Adult Female American English Speakers

Conversational entrainment, the natural tendency for people to modify their behaviors to more closely match their communication partner, is examined as one possible mechanism modulating the prevalence of vocal fry in the speech of young American women engaged in spoken dialogue.

http://ift.tt/2iD3FlA

Evaluation of lip force in patients with unilateral and bilateral cleft lip

Our aim was to investigate the differences in the dynamics of lip force between a group of participants with repaired cleft lips and a group of patients the same age but without clefts.We evaluated 101 children between the ages of 10 to 15 years (unilateral clefts n=35, bilateral clefts n=15, class I malocclusion n=25, and class III malocclusion n=26). Maximum and minimum forces required to close the lips were evaluated with the Lip De Cum® device (Cosmos Instruments Co Ltd, Tokyo, Japan) for the all groups.

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Success Rates and Complications From Eminectomies

Background: Eminectomy is a recognised treatment for temporomandibular joint dislocation and anterior meniscal displacement without reduction. Pneumatisation of the articular eminence has been described as an absolute contraindication to this procedure due to its associated complications. However comparing outcomes is difficult when a clear minimum data set is often not recorded.

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An alternative method of midface reconstruction: the use of customised PEEK implant and a laminate free soft tissue transfer

Introduction: Midface reconstruction remains a challenging area for most craniofacial surgeons. Free tissue transfer has been suggested as the method of choice for these complex three-dimensional maxillary reconstructions. These prolonged procedures carry significant risks and may not be the ideal treatment for all patients. Good functional and symmetric reconstructions of maxillary defect play significant part in preserving patients' quality of life. We present a case that incorporated the use of a patient-specific PEEK (polyether ether ketone) implant as an alternative to composite free tissue transfer to reconstruct an extensive maxillary defect.

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Pathways to limit group 2 innate lymphoid cell activation

Group 2 innate lymphoid cells (ILC2s) are a recently discovered population of lymphocytes that produce large amounts of TH2 cytokines.1 Unlike conventional T cells, ILC2s are not antigen specific and also lack specific lineage markers that identify other lymphocytes, including T, B, natural killer, and natural killer T cells. Mouse models of asthma have shown that ILC2s contribute to eosinophilic inflammation and hyperresponsiveness, and human studies have revealed increases in ILC2 counts in patients with asthma, allergic rhinitis, eosinophilic esophagitis, and atopic dermatitis.

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Assessing the therapeutic index of inhaled corticosteroids in children: Is knemometry the answer?

Since the introduction of topical inhaled corticosteroids (ICSs) for the treatment of asthma decades ago, there have been concerns about potential risks from systemic activity.1 This has been particularly true regarding ICS use in young children, in whom growth and development represent additional issues.2 Despite the ongoing development over the years of newer ICS molecules with pharmacokinetic properties that improve the therapeutic index (ratio of topical activity to systemic activity), such as decreased oral bioavailability, rapid systemic clearance, and lung retention (Fig 1), all ICSs still work by stimulating glucocorticoid receptors, which are found throughout the body.

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Insights into the mast cell–microbiome connection in the skin

Recent years have witnessed considerable advancement in the understanding of mast cell (MC) development and function in health and disease. MCs arise from CD34+ bone marrow–derived progenitors, but unlike other hematopoietic cells, they are not released to the blood circulation in a mature state.1 Rather, MC precursors home to peripheral tissues, where they reach full differentiation after birth under the influence of the local microenvironment. At this stage, they express the high-affinity IgE receptor FcεRI, along with the stem cell factor (SCF) receptor c-Kit, which is a critical determinant in their maturation, proliferation, and survival.

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Efficacy and safety of high-dose rush oral immunotherapy in persistent egg allergic children

Egg oral immunotherapy is effective but time consuming.

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Stratified premedication strategy for the prevention of contrast media hypersensitivity in high-risk patients

Although the severity of hypersensitivity reactions to iodinated contrast media varies, it is well correlated with the severity of recurrent reactions; however, prophylaxis protocols are not severity-stratified.

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Prevalence, risk factors, and clinical outcomes of atopic and nonatopic asthma among rural children

Because of time and cost constraints, objective classification of atopic and nonatopic asthma has been limited in large epidemiologic studies. However, as we try to better understand exposure-outcome associations and ensure appropriate treatment of asthma, it is important to focus on phenotype-defined asthma classification.

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Efficacy and safety of high-dose rush oral immunotherapy in persistent egg allergic children

Egg oral immunotherapy is effective but time consuming.

http://ift.tt/2jst4OW

Stratified premedication strategy for the prevention of contrast media hypersensitivity in high-risk patients

Although the severity of hypersensitivity reactions to iodinated contrast media varies, it is well correlated with the severity of recurrent reactions; however, prophylaxis protocols are not severity-stratified.

http://ift.tt/2j3mSQt

Prevalence, risk factors, and clinical outcomes of atopic and nonatopic asthma among rural children

Because of time and cost constraints, objective classification of atopic and nonatopic asthma has been limited in large epidemiologic studies. However, as we try to better understand exposure-outcome associations and ensure appropriate treatment of asthma, it is important to focus on phenotype-defined asthma classification.

http://ift.tt/2jsATUI

Audiologic and radiologic findings in cochlear hypoplasia

The aim of the current study is to evaluate audiologic and radiologic findings of cochlear hypoplasia which is a subgroup of inner ear malformations.

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Audiologic and radiologic findings in cochlear hypoplasia

The aim of the current study is to evaluate audiologic and radiologic findings of cochlear hypoplasia which is a subgroup of inner ear malformations.

http://ift.tt/2iDeggc

Conditional potency is a hallmark of viral protein-derived toxic peptides

Publication date: Available online 10 January 2017
Source:Medical Hypotheses
Author(s): Man Tang, Xiaoxia Li, Qizhang Li, Yanchao Zhou, Wen Pan, Jiayang Gao, Ziwei Ye, Shaoping Weng, Qiuyun Liu, Jianguo He, Zhumei He
Viral infections are major ongoing challenges to mankind. The theory of cytokine storm cannot fully account for the virulence of some highly infectious viruses with high mortality rates. Although numerous viruses are capable of lysing animal and human cells in vivo, viral protein-derived peptides are mostly mild in standard culture conditions in in vitro assays. A hypothesis is postulated that conditional potency of viral protein-derived toxic peptides could at least in part explain cell senescence upon viral infections. The hypothesis can be tested with full length viral proteins against microbial and mammalian cells in various media. Viral protein injections to live animals may reveal that they are critical factors underlying cell destructions when protein degradation pathways and cytokine levels are controlled. Stimulation of autophagy could enhance current viral therapies by recycling toxic viral proteins.



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Repair of 8-oxoG:A Mismatches by the MUTYH Glycosylase: Mechanism, Metals & Medicine

Publication date: Available online 10 January 2017
Source:Free Radical Biology and Medicine
Author(s): Douglas M. Banda, Nicole N. Nuñez, Michael A. Burnside, Katie M. Bradshaw, Sheila S. David
Reactive oxygen and nitrogen species (RONS) may infringe on the passing of pristine genetic information by inducing DNA inter- and intra-strand crosslinks, protein-DNA crosslinks, and chemical alterations to the sugar or base moieties of DNA. 8-Oxo-7,8-dihydroguanine (8-oxoG) is one of the most prevalent DNA lesions formed by RONS and is repaired through the base excision repair (BER) pathway involving the DNA repair glycosylases OGG1 and MUTYH in eukaryotes. MUTYH removes adenine (A) from 8-oxoG:A mispairs, thus mitigating the potential of G:C to T:A transversion mutations from occurring in the genome. The paramount role of MUTYH in guarding the genome is well established in the etiology of a colorectal cancer predisposition syndrome involving variants of MUTYH, referred to as MUTYH-associated polyposis. In this review, we highlight recent advances in understanding how MUTYH structure and related function participate in the manifestation of human disease such as MAP. Here we focus on the importance of MUTYH's metal cofactor sites, including a recently discovered "Zinc linchpin" motif, as well as updates to the catalytic mechanism. Finally, we touch on the insight gleaned from studies with MAP-associated MUTYH variants and recent advances in understanding the multifaceted roles of MUTYH in the cell, both in the prevention of mutagenesis and tumorigenesis.

Graphical abstract

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Thioredoxin a novel biomarker of post-injury sepsis

Publication date: Available online 10 January 2017
Source:Free Radical Biology and Medicine
Author(s): Jesper Eriksson, Andreas Gidlöf, Mikael Eriksson, Emma Larsson, Olof Brattström, Anders Oldner
BackgroundThioredoxin (TRX), an endogenous anti-oxidant protein induced in inflammatory conditions, has been shown to increase in plasma and to be associated with outcome in septic patients. This biomarker has never been studied in a trauma setting. We hypothesized that TRX would be increased after trauma and associated with post-injury sepsis.MethodsSingle-centre prospective observational study conducted at the intensive care unit (ICU) at the Karolinska University Hospital, Stockholm, Sweden, a level-1 trauma centre. Eighty-three severely injured trauma patients, 18 years or older, with an ICU stay of three days or more were included. Plasma samples were obtained on day 1 and 3 after informed consent. Clinical, physiological and outcome data were retrieved from the trauma and ICU research registries. Plasma samples were also obtained from 15 healthy subjects. In addition, a standardized porcine trauma model was conducted where a femur fracture followed by a controlled hemorrhage period were inflicted in four pigs.ResultsIn pigs, however not significant, there was a continuing increase in plasma-TRX after femur fracture and sequential hemorrhage despite near normalisation of cardiac index and lactate levels. In patients, median injury severity score was 29 and 48 patients developed sepsis during their ICU stay. A three-fold increase in initial TRX was seen in trauma patients when compared to healthy volunteers. Thioredoxin was significantly higher in patients in shock on admission, those subject to massive transfusion and in the most severely injured patients. No difference was seen between survivors and non-survivors. Plasma-TRX on day 1 was significantly increased in patients who later developed post-injury sepsis. In a logistic regression analysis including TRX, C-reactive protein, injury severity, massive transfusion, and admission blood pressure, TRX was the only variable independently associated with post-injury sepsis.ConclusionsThis study demonstrates that TRX is released into plasma in response to severe trauma and independently associated with post-injury sepsis. The use of TRX as a biomarker in trauma patients needs further evaluation in larger studies.Level of evidenceRetrospective cohort study, level III.

Graphical abstract

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Hypothyroidism in Cancer Patients on Immune Checkpoint Inhibitors with anti-PD1 Agents: Insights on Underlying Mechanisms

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-119528

Background: Immune therapy using monoclonal antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) for various cancers have been reported to cause thyroid dysfunction. Little is known, however, about the underlying pathogenic mechanisms and the course of hypothyroidism that subsequently develops. In this report, we use the change in thyroglobulin and thyroid antibody levels in patients on immune therapy who develop hypothyroidism to better understand its pathogenesis as well as examine the status of hypothyroidism in the long term. Methods: We report a case series of 10 patients who developed hypothyroidism after initiation of immune therapy (either anti-PD-1 alone or in combination with anti-CTLA-4). Available thyroid antibodies including anti-thyroglobulin (anti-Tg), anti-thyroid peroxidase (anti-TPO), and thyroid stimulating immunoglobulin (TSI) were noted during the initial thyroiditis phase as well as the hypothyroid phase. Persistence or remission of hypothyroidism was noted at 6 months. Summary: During the thyroiditis phase, 50% of the patients had elevated Tg titers, 40% had elevated anti-Tg, and 40% had elevated TSI. All of these titers decreased during the hypothyroid phase. Permanent hypothyroidism was noted in 80% of the cases. Conclusion: Hypothyroidism following initiation of immune therapy has immunologic and non-immunologic mediated mechanisms and is likely to be persistent.
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Alternative Treatment Strategies in Women Poorly Tolerating Moderate Doses of Bromocriptine

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-123041

Background: Metformin as well as dopaminergic agents exert a beneficial effect on glucose and lipid metabolism, often impaired in patients with hyperprolactinemia. Objective: The aim of this study was to compare metabolic- and prolactin-lowering effects of low-dose bromocriptine/metformin combination therapy and cabergoline in patients with elevated prolactin levels. Methods: The study included 27 women with hyperprolactinemia and impaired glucose tolerance who were treated with moderate doses of bromocriptine but experienced adverse effects of this treatment. In 12 of these patients bromocriptine was replaced with cabergoline (group A), while the remaining ones continued treatment with bromocriptine, the dose of which was halved, and administered together with metformin (group B). Plasma lipids, glucose homeostasis markers, as well as serum levels of prolactin, thyrotropin and insulin-like growth factor-1 (IGF-1) were assessed before and after 4 months of metformin treatment. Results: Both groups did not differ in baseline levels of plasma glucose and lipids, in insulin sensitivity, as well as in circulating levels of all measured hormones. All patients from group A and 12 patients from group B completed the study. Cabergoline reduced prolactin levels, while no effect on plasma prolactin was found in group B. Neither cabergoline nor bromocriptine plus metformin affected circulating levels of thyrotropin and IGF-1. Both treatment options, particularly low-dose bromocriptine plus metformin, improved glucose and lipid homeostasis. Conclusions: Low-dose bromocriptine combined with metformin may be an interesting alternative to cabergoline in patients with mild hyperprolactinemia and early glucose metabolism abnormalities, in whom moderate doses of bromocriptine are poorly tolerated.
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Evaluation of Glutathione Peroxidase and KCNJ11 Gene Polymorphisms in Patients with New Onset Diabetes Mellitus After Renal Transplantation

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-123040

Introduction Genetic mutations such as C599T polymorphism in glutathione peroxidase [GPX1] gene and polymorphisms in potassium channel (KCNJ11) genes have recently been proposed in the etiopathogenesis of new onset diabetes mellitus after renal transplantation (NODAT). We aimed to examine the association of GPX1 and KCNJ11 polymorphisms in NODAT. Materials and Methods This is a monocenter case-control study with a total of 118 renal transplant recipients who were divided into 2 groups; NODAT and normal glucose tolerance. Relation of GPX1 and KCNJ11 polymorphisms were investigated between these groups. PCR-RFLP method was used for genotyping of polymorphisms in the GPX1 (rs1050450) and KCNJ11 (rs1805127) genes. Two alleles were visualized for each gene (C/T for GPX1 and A/G for KCNJ11). Results NODAT was correlated with age at transplantation (p<0.001, r=0.380), post-transplant systolic blood pressure (BP) (p=0.02, r=0.211), post-transplant non-HDL cholesterol levels (p=0.01, r=0.803), degree of weight change at the end of the first year (p=0.01, r=0.471), presence of pre-transplant hypertension (HT) (p=0.02, r=0.201), family history of diabetes (p=0.01, r=0.29) and dyslipidemia (p=0.012, r=0.362). GPX1 polymorphism of TT (mutant) allele was significantly more frequent in patients with NODAT (p<0.001, r=0.396) independent from other diabetogenic risk factors. KCNJ11 polymorphisms were similar in both groups and did not show any significant association with NODAT (p=0.10). Conclusions In addition to several diabetogenic risk factors, C599T polymorphisms in GPX1 gene might also contribute to the development of NODAT. Further studies on larger patient series are necessary in order to reach definitive suggestions.
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Long-term Consequences of Congenital Adrenal Hyperplasia due to Classic 21-hydroxylase Deficiency in Adolescents and Adults

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-123037

Background The management of congenital adrenal hyperplasia (CAH) from pediatric to adulthood is challenging to achieve optimal growth and puberty. This study characterizes the clinical outcomes of 21-hydroxylase deficiency. Methods 53 CAH patients were included (33 females, 15 and 18 patients with the salt-wasting [SW] and simple-virilizing [SV] forms; and 20 males, 16 and 4 patients with the SW and SV forms). We reviewed growth parameters, pubertal status, and long-term morbidities. Results In females, the age at pubertal onset and pubarche was 9.6±0.9 and 10.5±1.9 years, respectively, which was significantly earlier in the SV form (p=0.005). In males, the ages at pubertal onset and pubarche were 10.1±2.0 and 10.7±2.5 years, respectively, which were not significantly different between the groups. Forty patients reached adult height: −2.1±1.6 SDS in males and −1.5±1.1 SDS in females. Obesity and overweight was significantly common in adult patients. Testicular adrenal rest tumors were found in 4 SW males. 5 patients had adrenal tumor including adenoma, adenocarcinoma, or myelolipoma. Conclusions Reduced adult height and obesity/overweight are prevalent in adulthood. Adolescents and adults with 21-hydroxylase deficiency should be monitored for long-term consequences.
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The Effects of Blood Glucose Regulation in Omentin-1 Levels among Diabetic Patients

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-118862

Objectives: Omentin-1, an adipocytokine that increases the insulin sensitivity, has been determined to be reduced in patients with insulin resistance, impaired glucose tolerance, and Type-2 diabetes mellitus. In this study, we have investigated the alterations in Omentin-1 levels with the blood glucose regulation in diabetic patients having poor glycemic control. By this way, we aimed to determine the role of Omentin-1 as a marker in follow-up and monitoring progression of diabetes. Methods: Totally 58 patients with type 2 diabetes mellitus, older than 18 years of age who were having poor glycemic control (HbA1c≥9) were included in this study. In the first visit, all clinical and biochemical parameters of patients were recorded. After baseline evaluation, the patients were advised life style changes, and their medical treatment was determined individually according to the recommendations of the American Diabetes Association guidelines. At the end of the third month patients were re-evaluated. Serum Omentin-1 levels were measured with ELISA. Results: In patients using only oral antidiabetic agents, after exchanging the treatment with insulin, on 3rd month of treatment, there was a significant decrease in serum C-peptide and Omentin-1 levels compared with the initial results (p=0.034, p=0.048, respectively). On the other hand, in patients using insulin treatment from the beginning of the study, there was not any significant alterations in serum C-peptide or Omentin-1 levels compared with the initial results (p>0.05). Conclusions: Serum Omentin-1 levels may change with insulin and metformin treatments in Type-2 diabetic patients. In patients with poor glycemic control, Omentin-1 levels do not change with the regulation of blood glucose levels. A decrease in Omentin-1 and C-peptide levels has been determined after the initiation of insulin therapy. This suggests that, Omentin-1 levels are closely associated with the endogenous insulin reserve and may be used in follow-up of patients.
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Osteocalcin Improves Metabolic Profiles, Body Composition and Arterial Stiffening in an Induced Diabetic Rat Model

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-122138

Recent studies have demonstrated the benefits of osteocalcin (OCN) on glucose homeostasis and metabolic dysregulation. However, its role in body composition and vascular function remains unknown. This study was designed to examine changes in metabolic parameters and body composition as well as arterial stiffness after OCN treatment in type 2 diabetic rats. Adult male Sprague Dawley (SD) rats were fed chow or high fat diet (HFD) for 8 weeks, and then diabetes was induced with an injection of low-dose streptozotocin (STZ) and treated daily with intraperitoneal injections of OCN for 12 weeks. Our data showed that OCN treatment improved glucose homeostasis and lipid metabolism. Further analysis revealed that OCN treatment resulted in increased insulin sensitivity. In addition, untreated diabetic rats experienced significant weight loss, whereas OCN-treated rats better maintained body weight (300.75±38.14 g vs. 335.50±23.70, p=0.005). OCN also changed body composition, as evidenced by reduced body fat mass, specifically abdominal fat mass. OCN-treated diabetic rats also demonstrated decreased pulse-wave velocity, indicating of improved arterial stiffness. Taken together, our findings in the current study revealed that OCN therapy prevents arteriosclerosis in an induced diabetic rat model by exerting beneficial effects on glucose levels, insulin sensitivity, lipid metabolites, and body composition changes.
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The Effect of Vitamin D on Thyroid Autoimmunity in Levothyroxine-Treated Women with Hashimoto’s Thyroiditis and Normal Vitamin D Status

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-123038

Background: Low vitamin D status is associated with autoimmune thyroid disease. Oral vitamin D supplementation was found to reduce titers of thyroid antibodies in levothyroxine-treated women with postpartum thyroiditis and low vitamin D status. Methods: The study included 34 women with Hashimoto's thyroiditis and normal vitamin D status (serum 25-hydroxyvitamin D levels above 30 ng/mL) who had been treated for at least 6 months with levothyroxine. On the basis of patient preference, women were divided into 2 groups, receiving (n=18) or not receiving (n=16) oral vitamin D preparations (2000 IU daily). Serum levels of thyrotropin, free thyroxine, free triiodothyronine and 25-hydroxyvitamin D, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later. Results: There were no significant differences in baseline values between both study groups. 25-hydroxyvitamin D levels inversely correlated with titers of thyroid antibodies. No changes in hypothalamic-pituitary-thyroid axis activity and thyroid antibody titers were observed in vitamin-naïve patients. Vitamin D increased serum levels of 25-hydroxyvitamin D, as well as reduced titers of thyroid antibodies. This effect was more pronounced for thyroid peroxidase than for thyroglobulin antibodies and correlated with their baseline titers. Conclusions: Vitamin D preparations may reduce thyroid autoimmunity in levothyroxine-treated women with Hashimoto's thyroiditis and normal vitamin D status.
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Brown and White Adipose Tissue Expression of IL6, UCP1 and SIRT1 are Associated with Alterations in Clinical, Metabolic and Anthropometric Parameters in Obese Humans

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-119525

Aim: The present study aimed to analyze the expression of IL6, UCP1 and SIRT1 in adipose tissue (WAT and BAT) in association to clinical, metabolic and anthropometric parameters in obese humans. Methods: WAT and BAT samples from obese patients (n=27) were collected. IL6, UCP1 and SIRT1 markers were measured by qRT-PCR. The association between IL6, UCP1 and SIRT1 mRNA expression and anthropometric and clinical parameters were evaluated, using appropriate statistical tests. Results: Our results demonstrated that high levels of IL6 are associated with altered glucose levels in the WAT (p=0.01). In contrast, high levels of IL6 in the BAT were associated with decreased % fat (p=0.01) and fat weight (p=0.02) and increased mVO2 (p=0.02) and VO2 (p=0.02). For UCP1, a higher expression in the BAT was observed when compared to the WAT (p=0.0001). This gene expression was associated with lower values of BMI (p=0.03), % fat (P=0.02) and fat weight (P=0.02) and increased mVO2 (p=0.041) and VO2 (p=0.001). In the WAT, decreased levels of SIRT1 were associated with increased fat weight (p=0.02); in the BAT, associations were found for % fat (p=0.018) and mVO2 (p=0.03). Conclusion: These results reveal different characteristics in the biological actions between WAT and BAT in obese humans. Increased levels of IL6, UCP1 and SIRT1 in the BAT were associated with metabolic parameters improvements.
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