Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Δευτέρα 11 Ιουνίου 2018

Dedication

Publication date: Available online 11 June 2018
Source:Radiologic Clinics of North America
Author(s): Savvas Nicolaou, Mohammed F. Mohammed




https://ift.tt/2sSCo5C

Prefrontal D1 Dopamine-Receptor Neurons and Delta Resonance in Interval Timing

Abstract
Considerable evidence has shown that prefrontal neurons expressing D1-type dopamine receptors (D1DRs) are critical for working memory, flexibility, and timing. This line of work predicts that frontal neurons expressing D1DRs mediate cognitive processing. During timing tasks, one form this cognitive processing might take is time-dependent ramping activity—monotonic changes in firing rate over time. Thus, we hypothesized the prefrontal D1DR+ neurons would strongly exhibit time-dependent ramping during interval timing. We tested this idea using an interval-timing task in which we used optogenetics to tag D1DR+ neurons in the mouse medial frontal cortex (MFC). While 23% of MFC D1DR+ neurons exhibited ramping, this was significantly less than untagged MFC neurons. By contrast, MFC D1DR+ neurons had strong delta-frequency (1–4 Hz) coherence with other MFC ramping neurons. This coherence was phase-locked to cue onset and was strongest early in the interval. To test the significance of these interactions, we optogenetically stimulated MFC D1DR+ neurons early versus late in the interval. We found that 2-Hz stimulation early in the interval was particularly effective in rescuing timing-related behavioral performance deficits in dopamine-depleted animals. These findings provide insight into MFC networks and have relevance for disorders such as Parkinson's disease and schizophrenia.

https://ift.tt/2sQG6g1

Neural Overlap in Item Representations Across Episodes Impairs Context Memory

Abstract
We frequently encounter the same item in different contexts, and when that happens, memories of earlier encounters can get reactivated. We examined how existing memories are changed as a result of such reactivation. We hypothesized that when an item's initial and subsequent neural representations overlap, this allows the initial item to become associated with novel contextual information, interfering with later retrieval of the initial context. Specifically, we predicted a negative relationship between representational similarity across repeated experiences of an item and subsequent source memory for the initial context. We tested this hypothesis in an fMRI study, in which objects were presented multiple times during different tasks. We measured the similarity of the neural patterns in lateral occipital cortex that were elicited by the first and second presentations of objects, and related this neural overlap score to subsequent source memory. Consistent with our hypothesis, greater item-specific pattern similarity was linked to worse source memory for the initial task. In contrast, greater reactivation of the initial context was associated with better source memory. Our findings suggest that the influence of novel experiences on an existing context memory depends on how reliably a shared component (i.e., item) is represented across these episodes.

https://ift.tt/2LHYVJm

Relationships Between Neuronal Oscillatory Amplitude and Dynamic Functional Connectivity

Abstract
Event-related fluctuations of neural oscillatory amplitude are reported widely in the context of cognitive processing and are typically interpreted as a marker of brain "activity". However, the precise nature of these effects remains unclear; in particular, whether such fluctuations reflect local dynamics, integration between regions, or both, is unknown. Here, using magnetoencephalography, we show that movement induced oscillatory modulation is associated with transient connectivity between sensorimotor regions. Further, in resting-state data, we demonstrate a significant association between oscillatory modulation and dynamic connectivity. A confound with such empirical measurements is that increased amplitude necessarily means increased signal-to-noise ratio (SNR): this means that the question of whether amplitude and connectivity are genuinely coupled, or whether increased connectivity is observed purely due to increased SNR is unanswered. Here, we counter this problem by analogy with computational models which show that, in the presence of global network coupling and local multistability, the link between oscillatory modulation and long-range connectivity is a natural consequence of neural networks. Our results provide evidence for the notion that connectivity is mediated by neural oscillations, and suggest that time–frequency spectrograms are not merely a description of local synchrony but also reflect fluctuations in long-range connectivity.

https://ift.tt/2JyPqQp

Effects of laser therapy on patients who underwent rapid maxillary expansion; a systematic review

Abstract

Rapid maxillary expansion (RME) is one of the common treatments of transverse maxillary deficiency, and low-level laser therapy (LLLT) is one of the recommended solutions to enhance biological wound or bone healing. This review article aims to answer the following question: "What are the effects of LLLT, on patients who underwent surgical or non-surgical RME, in improving clinical success, wound healing, and bone regeneration?" A search in PubMed, Scopus, Web of Science, and ProQuest databases was performed, with a focus on the appropriate key words. Related articles, up to May 2017, were screened, and the full text of the randomized controlled trials (RCT) were comprehensively read and subjected to quality assessments. A total of 1804 articles were included after the initial search. Four RCTs were eligible in randomization and methodology. The applied wavelength varied from 660 to 830 nm with an output range of 40–100 mW. Also, the highest exposed energy was 420 J/cm2 and the lowest was 100 J/cm2. The exposure time differed from 20 to 84 s in each defined point in the palate. Based on the RCTs available, LLLT is better to be used at initial phase of RME, because it has some benefits in increasing the rate of bone remodeling.



https://ift.tt/2LKIonV

Fellatio-associated erythema of the soft palate: an incidental finding during a routine dental evaluation

Oral lesions can have widely variable aetiology, hence, the importance of a comprehensive history and oral examination. We describe the case of a 47-year-old man who presented with an incidental erythematous lesion of the soft palate. The diagnosis was established during a routine dental examination. We found the lesion to be associated with the practice of fellatio. Oral sex is a very common sexual practice, and as clinicians we should consider it as a potential cause of palatal lesions in our differential diagnosis. This should also raise our suspicion for sexually transmitted diseases in high-risk patients.



https://ift.tt/2l2DdVe

Recurrent meningitis caused by idiopathic cerebrospinal fluid rhinorrhoea from the sphenoid sinus

Description

A 41-year-old woman with 7 days of fever and headache had loss of consciousness 1 day prior to presentation. Despite the absence of trauma or other significant medical history, she had two episodes of meningitis in the previous 6 months. Physical examination showed no nuchal rigidity or abnormal findings on nasal endoscopy. Lumbar puncture showed a cerebrospinal fluid cell count of 750/μl. CT showed a bony defect of the posterior wall of the sphenoid sinus, which was filled with a soft tissue density. MRI showed fluid intensity in the same area (figure 1A, B). The diagnosis was recurrent meningitis due to possible idiopathic cerebrospinal fluid rhinorrhoea. Although a cisternogram is normally recommended, emergency drainage of the sphenoid sinus with antibiotic treatment was prioritised because of her deteriorating condition. With various possible diagnoses, an experienced surgeon operated on the patient. 

Figure 1

A bony defect of...



https://ift.tt/2y61F1k

Management of placenta percreta in a Jehovahs Witness patient

Placenta percreta is increasing in incidence and is associated with the risk of life-threatening haemorrhage. Patients who do not accept blood products present a unique challenge to obstetrician-gynaecologists. In this case report, we present the case of a 42-year-old pregnant Jehovah's Witness with a complete placenta previa and confirmed percreta at 26 weeks' gestation. Due to her religious beliefs against the use of blood products, she was managed with a stepwise surgical approach which involved caesarean delivery with internal iliac (hypogastric) artery ligation, weekly methotrexate and delayed hysterectomy 6 weeks later. Non-traditional, alternative approaches to the management of abnormal placentation in patients declining blood products warrant exploration.



https://ift.tt/2l5DOpe

Persistent elevation of carcinoembryonic antigen as first presentation of a medullary thyroid carcinoma

Carcinoembryonic antigen (CEA) is still the most widely used tumour marker for gastrointestinal cancer. CEA was originally thought to be a specific marker for colorectal cancer, but it turned out to be a non-specific marker for further studies. CEA levels can be elevated in breast, lung and liver cancers, among others, including medullary thyroid cancer. The authors report a case of a 73-year-old woman who had a right hemicolectomy for an ascending colon adenocarcinoma and showed a persistent elevation in the CEA marker during follow-up. After several imaging tests, recurrence of the colon cancer was not found, but the presence of thyroid nodules had been detected. The diagnosis of a medullary thyroid carcinoma was made after the finding of a high value of calcitonin. The patient had a total thyroidectomy with resection of the central and lateral lymph nodes.



https://ift.tt/2y4BUP4

Bronchogenic cyst infection presenting as pleuropericarditis

Description 

A 17-year-old woman was admitted to the emergency department with a 3-day history of dyspnoea (New York Heart Association Class II) and typical pleuritic pain following a 1-week history of cough and fever. Pneumonia was diagnosed based on a chest X-ray (figure 1A), and amoxicillin–clavulanate treatment was initiated. After 48 hours, the patient developed hypotension and tachycardia. Given hypotension, ongoing fever and rising C reactive protein despite antibiotic treatment, she was referred to the intensive care unit. On admission, an echocardiography was performed. A circumferential pericardial effusion with 14 mm maximum diameter adjacent to the right ventricle was detected, without haemodynamic compromise at the time. Besides, left pleural effusion was evidenced. An ultrasound-guided thoracentesis was conducted. Pleural fluid testing revealed the following findings: white blood cells (WBC) count 11.109/Literwith 90% neutrophils, proteins 38 g/L, pH 7.36, glucose 6.3 mmol/L and lactate dehydrogenase (LDH) 492 IU/L. The culture exhibited no organism,...



https://ift.tt/2l2DbwA

Dentin dysplasia: diagnostic challenges

Dentin dysplasia(DD) is a rare autosomal dominant disorder associated with disturbance of the dentin. While the crowns appear clinically normal, on radiography, the pulp spaces appear partially or completely obliterated, with short blunted roots, and multiple periapical radiolucencies affecting the apparently sound teeth. Clinical signs include spontaneous abscess formation or increased tooth mobility which can lead to exfoliation. DD can therefore have a significant impact on the patient's dentition, and treatment is often challenging. Shields' classification of dentin disorders has been recently criticised for failing to consider differential variations and expressions of these disorders. This paper describes a case of a 23-year-old woman with previously undiagnosed DD, who presented with clinical and histological features belonging to several of these diseases, thus highlighting the potential diagnostic challenges faced with Shields' classification.



https://ift.tt/2l2D9Vu

Osteoporosis and malignancy: a dicey combination

Osteoporosis is the most common metabolic bone disorder worldwide, especially in women. Postmenopausal status is the most common risk factor for osteoporosis in elderly women. The operational diagnosis of osteoporosis is usually made with the help of central dual energy X-ray absorptiometry scan. Clinically, osteoporosis is suspected in the background of one or more fractures of the hip, vertebra, proximal humerus or pelvis in the absence of local disease or high-energy trauma. Serious underlying illness can present with vertebral fractures and can be missed if other clues from clinical examination and investigations are overlooked. We report a case emphasising this aspect.



https://ift.tt/2y61BP8

Primary carnitine deficiency in a 57-year-old patient with recurrent exertional rhabdomyolysis

Rhabdomyolysis is an emergency requiring rapid diagnosis and suitable aetiological treatment. We describe the case of a 57-year-old man with recurrent exertional rhabdomyolysis who was diagnosed with systemic primary carnitine deficiency (SPCD). Clinical examination was normal, creatine kinase levels were elevated, plasma free carnitine concentration was mildly decreased, muscle biopsy demonstrated lipid accumulation, carnitine uptake in cultured fibroblasts was decreased and genetic analysis identified a homozygous pathologic c.1181_1183del in the SLC22A5 gene. Rhabdomyolysis did not recur after treatment with oral L-carnitine was introduced. SPCD is a rare autosomal recessive disorder of carnitine transportation usually manifesting as an infantile (hepatic) or a childhood myopathic (cardiac) condition and rarely affecting adults. Our case indicates that SPCD should be considered in the aetiological evaluation of adult patients with recurrent exertional rhabdomyolysis, even in the absence of myopathy and cardiomyopathy.



https://ift.tt/2l5DK8Y

Horseshoe kidney with unilateral single ectopic ureter

The horseshoe kidney (HSK) is not an uncommon entity with an incidence of about 1 in 400 or 0.25% of the general population. It is also more commonly found in men as compared with women in a ratio of 2:1.An increased association of genitourinary anomalies have been found with HSK.Duplication of ureters occurs in 10% of HSKs. However, the association of HSK with single-system ectopic ureter is extremely rare. To our knowledge, no case with similar presentation has been reported in literature. Most cases of HSK with bilateral single ectopic ureters have been described. The aim of this report is to highlight the radiological and surgical findings in a case of HSK with unilateral single ectopic ureter.



https://ift.tt/2y61Ae2

Traumatic corneal perforation with exteriorisation of Ahmed glaucoma valve tube

We report a rare case of traumatic corneal perforation with Ahmed glaucoma valve (AGV) tube. A 5-year-old female child, diagnosed with refractory glaucoma, had undergone AGV implantation, presented with the posterior migration of AGV tube after trauma to the eye. The detailed ocular history, ophthalmic findings, clinical course and surgical management are discussed.



https://ift.tt/2l2D6cg

Metachronous renal Ewing sarcoma/primitive neuroectodermal tumour in a survivor of Burkitt lymphoma

We present a case of a 14-year-old girl who was diagnosed with Burkitt lymphoma in 2014. She was managed with chemotherapy and remained in remission for 3 years. On her surveillance imaging in 2017, a left-sided renal neoplastic mass was incidentally discovered. She underwent nephrectomy and pathology of the resected specimen revealed small cell tumour of the kidney with features favouring renal Ewing sarcoma/primitive neuroectodermal tumour. Molecular genetic analysis by fluorescence in situ hybridisation was performed which showed translocation of 22q12, thereby confirming the diagnosis. This is a rare secondary malignancy and an unusual association. This case highlights the importance and diagnostic dilemmas of rare secondary tumours in patients with such haematological malignancies and discusses its possible pathogenetic aspects.



https://ift.tt/2y61yCW

Green synthesis of gold nanoparticles using Artemisia dracunculus extract: control of the shape and size by varying synthesis conditions

Abstract

In this study, selective green synthesis of gold nanoparticles (nAu) with the use of Tarragon extract (Artemisia dracunculus) was investigated. Characterization of the synthetized nAu was carried out using several techniques including: UV-Vis, SEM, zeta potential analysis, DLS, and ATR-FTIR. Based on measurements of Tarragon extract by HPLC-MS, significant chemical substances participating as reducing and stabilizing agents were identified. FTIR confirmed typical functional groups that could be found in these acids on the nAu surface, such as O-H, C=O and C-O. The effects of various parameters (concentration of Tarragon extract, Au precursor, and initial pH of the synthesis) on the shape and size of the nanoparticles have been investigated. UV-Vis and SEM confirmed the formation of nAu at various concentrations of the extract and Au precursor and showed correlation between the added extract concentration and shift in maximal absorbance towards higher frequencies, indicating the formation of smaller nanoplates. Zeta potential determined at various pH levels revealed that its value decreased with pH, but for all experiments in the pH range of 2.8 to 5.0, the value is below − 30 mV, an absolute value high enough for long-term nAu stability. In order to evaluate nAu catalytic activity, the reduction of 4-nitrophenol to 4-aminophenol by sodium borohydride was used as a model system. The reaction takes place 1.5 times faster on Au-triangles than on Au-spherical NPs.



https://ift.tt/2sNLSiM

Emissions of selected brominated flame retardants from consumer materials: the effects of content, temperature, and timescale

Abstract

The ubiquitous presence of brominated flame retardants (BFRs) in indoor air, dust, and even in human tissue could be attributed to their emissions from BFR-containing products. Nevertheless, the emission behavior of BFRs, especially novel BFRs from consumer materials, to the indoor environment has still not been well understood. To evaluate the effects of chemical content, temperature, and time on the emissions of BFRs, we used a batch of small glass chambers to conduct emission tests on carpet, computer casings, sound insulation, circuit boards, decorative laminate, and PVC floors at temperatures from 20 to 80 °C, as well as different emission times of up to 35 days. Seven BFRs were extracted from the tested materials with contents ranging from 50 to 35,803 μg g−1, and four BFRs were detected with emission rates between 5.9 and 418 pg g−1 h−1 at room temperature (20 °C); 1,2,5,6,9,10-hexabromocyclododecane (HBCD) was considered to be the dominant compound, which was found in and could be emitted from all of the tested materials. Emission rates are significantly and positively correlated with both the contents of tested materials and the elevated temperature. These results indicate that BFR-containing products have the potential to be a major source of indoor contamination.



https://ift.tt/2t0R422

Thank you list 2017



https://ift.tt/2t1n1qP

Androgen receptor in triple negative breast cancer: A potential target for the targetless subtype

S03057372.gif

Publication date: Available online 11 June 2018
Source:Cancer Treatment Reviews
Author(s): L. Gerratana, D. Basile, G. Buono, S. De Placido, M. Giuliano, S. Minichillo, A. Coinu, F. Martorana, I. De Santo, L. Del Mastro, M. De Laurentiis, F. Puglisi, G. Arpino
Triple negative breast cancer (TNBC) represents the 15-20% of all breast cancers (BC) and is characterized by a very aggressive behavior. Recent data suggest that TNBC is not a single disease, but it is rather an umbrella for different ontology-profiles such as basal like 1 and 2, mesenchymal, and the luminal androgen receptor (LAR). The LAR subtype is characterized by the expression of the Androgen Receptor (AR) and its downstream effects. Notwithstanding the role of the AR in several signaling pathways, its impact on a biological and clinical standpoint is still controversial. The LAR subtype has been associated with better prognosis, less chemotherapy responsiveness and lower pathologic complete response after neoadjuvant treatment. Clinical evidence suggests a role for anti-androgen therapies such as bicalutamide, enzalutamide and abiraterone, offering an interesting chemo-free alternative for chemo-unresponsive patients, and therefore potentially shifting current treatment strategies.



https://ift.tt/2y0h1o5

Fallopian Tube Tumorigenesis and Clinical Implications for Ovarian Cancer Risk-Reduction

S03057372.gif

Publication date: Available online 11 June 2018
Source:Cancer Treatment Reviews
Author(s): Allison Gockley, Kevin M. Elias
Ovarian cancer remains the leading cause of gynecologic cancer death among American women. Prevention is the only proven approach to reduce the incidence of the disease. Oral contraception, tubal ligation, and risk-reducing salpingo-oophorectomy (rrBSO) for high-risk groups are all established risk reduction strategies. This paradigm is changing as recent biologic studies suggest that many ovarian cancers, especially high-grade serous ovarian cancers, originate in the distal end of the fallopian tube rather than the ovarian surface epithelium. A putative precursor lesion has been identified called the serous tubal intraepithelial carcinoma (STIC). Theoretically, removal of the fallopian tubes alone may prevent these lesions and prevent overt disease. Opportunistic salpingectomy during benign gynecologic surgery appears to be safe and may offer some protection from ovarian cancer without compromising ovarian endocrine function. Despite a lack of evidence for efficacy, several professional societies now recommend this approach for average-risk women. Whether salpingectomy can also serve as a temporizing measure to delay risk-reducing oophorectomy in women with a genetic predisposition to ovarian cancer remains to be seen. Several ongoing non-randomized clinical trials will test the feasibility of this approach. Therefore, the societal impact of increasing salpingectomy rates on ovarian cancer incidence will be an area of intense focus for the next 10-20 years.



https://ift.tt/2Jw8iiL

Mussel-inspired catalytic selenocystamine-dopamine coatings for long-term generation of therapeutic gas on cardiovascular stents

Publication date: September 2018
Source:Biomaterials, Volume 178
Author(s): Zhilu Yang, Ying Yang, Li Zhang, Kaiqin Xiong, Xiangyang Li, Feng Zhang, Jin Wang, Xin Zhao, Nan Huang
The development of a nitric oxide (NO)-generating surface with long-term, stable and controllable NO release improves the therapeutic efficacy of cardiovascular stents. In this work, we developed a "one-pot" method inspired by mussel adhesive proteins for copolymerization of selenocystamine (SeCA) and dopamine (Dopa) to form a NO-generating coating on a 316 L stainless steel (SS) stent. This "one-pot" method is environmentally friendly and easy to popularize, with many advantages including simple manufacturing procedure, high stability and no involvement of organic solvents. Such SeCA/Dopa coatings also enabled us to develop a catalytic surface for local NO-generation by reaction of endogenously existing S-nitrothiol species from fresh blood. We found that the developed SeCA/Dopa coatings could release NO in a controllable and stable manner for more than 60 days. Additionally, the released NO significantly inhibited smooth muscle cell (SMC) proliferation and migration, as well as platelet activation and aggregation through the up-regulation of cyclic guanosine monophosphate synthesis. Moreover, such NO generation enhanced the adhesion, proliferation and migration of endothelial cells (ECs), and achieved rapid in vivo re-endothelialization, effectively reducing in-stent restenosis and neointimal hyperplasia. We envision that the SeCA/Dopa-coated 316 L SS stent could be a promising platform for treatment of cardiovascular diseases.

Graphical abstract

image


https://ift.tt/2JQvwjb

Neurotization of nasal mucosa by end-to-side nerve graft: preliminary report of smell restoration

Abstract

Nerve regeneration after an end-to-side neurorrhaphy had been well established in the literature. Both sensory and motor functions could be achieved using this technique. Autonomic and special sensory restoration (e.g., smell sensation) were not studied extensively before. Post-traumatic anosmia has an overall prevalence rate of 7%, with a variable rate of recovery. In this preliminary report, olfactory sensation was restored in a case with a long-standing anosmia using end-to-side nerve graft. The patient reported regaining of smell, which was confirmed by a smell identification test. This technique has the potential to be a promising method for smell restoration; however, it needs further workup and investigations.

Level of Evidence: Level V, therapeutic study.



https://ift.tt/2JLzNUU

Thyroid Hormone Receptors Regulate the Expression of microRNAs with Key Roles in Skin Homeostasis

Thyroid, Ahead of Print.


https://ift.tt/2Mj3ds2

Bone Marrow Versus Peripheral Blood as a Graft Source for Haploidentical Donor Transplantation in Adults Using Post-Transplant Cyclophosphamide—A Systematic Review and Meta-Analysis

Publication date: Available online 11 June 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Xiaotong Yu, Liping Liu, Zhenwei Xie, Chongya Dong, Libo Zhao, Jingru Zhang, Hong-Hu Zhu, Jian Gu
BackgroundPeripheral-blood (PB) and bone marrow (BM) are both widely used in hematopoietic stem cell transplantation (HSCT). However, it is unclear whether PB or BM produces a more satisfactory outcome in haploidentical HSCT, particularly for patients using post-transplant cyclophosphamide (PTCy), which is the standard therapy. However, to date, no meta-analysis focusing on this issue has been published.MethodsWe systematically searched PubMed, MEDLINE, Web of Science, the Cochrane Library and the ClinicalTrials.gov website for studies regarding the use of BM or PB in haploidentical HSCT for hematological malignancies in adults using PTCy. Data were analyzed using Open Meta-Analyst statistical software.ResultsFourteen studies were extracted including four comparative retrospective reports and ten single-arm reports, with a total of 1759 patients received PTCy haploidentical HSCT (462 patients received PBSCT, 1297 patients received BMT). The pooled outcomes of comparative retrospective studies showed significantly higher incidence of grade III-IV acute graft-versus-host disease (GVHD) (OR = 1.741, 95%CI 1.032-2.938), incidence of grade II-IV acute GVHD (OR = 1.778, 95%CI 1.314, 2.406) and engraftment rate (OR = 1.843, 95%CI 1.066-3.185) in the PB group. No significant differences were found on the incidence of relapse, 2-year overall survival (OS) and disease-free survival (DFS), acute II-IV GVHD and chronic GVHD between PBSCT or BMT.ConclusionThe efficacy of PB is not inferior to BM for patients undergoing PTCy haploidentical HSCT with regard to primary outcomes, including OS, DFS, NRM and relapse. However, with regards to convenience and pain relief, PB graft is suitable for haploidentical HSCT, but with a higher risk of acute GVHD.



https://ift.tt/2JFvyXH

Targeting the cellular schizophrenia. Likely employment of the antipsychotic agent pimozide in treatment of refractory cancers and glioblastoma

Publication date: Available online 11 June 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Ilhan Elmaci, Meric A. Altinoz
Pimozide is currently being used in clinic as a neuroleptic and exerts versatile biological actions. Pimozide is a cationic amphiphilic drug (CAD); CADs block the synthesis of neutral lipids, impair cholesterol homeostasis of cancer cells and increase accumulation of diacylglycerol-3-phosphate. Pimozide exerts tumoricidal activity which was first shown for melanoma and neuroblastoma via proposed anti- dopaminergic effects. Recently, pancreas cancers are shown to elevate dopamine receptor-2 synthesis, which is blocked by pimozide leading growth inhibition. Besides binding to inner mitochondrial membrane and reducing cellular respiration, pimozide also inhibits calmodulin, T-type calcium channels and σ-receptors which all correlate with tumor-inhibitory functions. Pimozide also exerts chemotherapy and radiotherapy-sensitizing effects in cancer cells and acts as an inhibitor of STAT-3 and STAT-5 signaling proteins with potential activity in leukemia, liver and prostate cancer. Pimozide also blocks stem cell features and Wnt-β/catenin signaling in liver cancer. Pimozide interferes with Fatty Acid Protein Binding-4 and activates PPAR-γ and it was proposed to alleviate cancer cachexia. Besides mechanisms of calmodulin and σ-receptor associated pathways, pimozide was proposed to inhibit glioblastoma via serotonin receptor 5-HT7. Pimozide is a selective inducer of autophagy and also inhibits ubiquitine specific protease (USP-1) which may associate with its chemosensizing potential in lung cancer and glioblastoma. Via versatile mechanisms of tumoricidal actions and due to its highly traversing capability through the blood-brain barrier, pimozide highly deserves to be studied in animal models of drug resistant refractory cancers and glioblastoma, which have very poor prognosis.



https://ift.tt/2y8ZoCK

Leserbrief zu Ellies M. Aus der Gutachtenpraxis: Was ist eine Biopsie mit Inzision? Begutachtung der Kodierung im G-DRG-System in der HNO-Heilkunde. Laryngo-Rhino-Otol 2018; 97: 203–205

10-1055-a-0612-9553-1.jpg

Laryngo-Rhino-Otol 2018; 97: 373-373
DOI: 10.1055/a-0612-9553



© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text



https://ift.tt/2sQq1XN

Stapedotomie erfolgreich bei fortgeschrittener Otosklerose?

10-1055-s-0044-100282-1.jpg

Laryngo-Rhino-Otol 2018; 97: 369-370
DOI: 10.1055/s-0044-100282

Heining et al. Audiological outcome of stapes surgery for far advanced cochlear otosklerosis. J Laryngol Otol 2017; 131: 961–964 Die cochleäre Otosklerose ist eine seltene Erkrankung des Innenohres, die zu einer Verknöcherung der Haarzellen führt und die Homöostase der Lymphströme negativ beeinflussen kann. Betroffene leiden unter Innenohrschwerhörigkeit, eine Therapie gilt als schwierig. Heining und Kolleginnen/Kollegen haben nun in einer retrospektiven Studie untersucht, ob Patienten mit fortgeschrittener Otosklerose von einer Stapedotomie profitieren können.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2JGM3T6

Spasmodische Dysphonie: Langzeitergebnisse mit Thyroplastik Typ 2

Laryngo-Rhino-Otol 2018; 97: 370-372
DOI: 10.1055/s-0043-121841

Sanuki T et al. Long-term Evaluation of Type 2 Thyroplasty with Titanium Bridges for Adductor Spasmodic Dysphonia. Otolaryngol Head Neck Surg 2017; 157: 80–84 Japanische Ärzte für Hals-, Nasen- und Ohrenheilkunde sowie Kopf- und Halschirurgie berichteten über stimmliche Langzeitergebnisse nach Durchführung einer Thyroplastik Typ 2 zur Behandlung der spasmodischen Dysphonie vom Adduktor Typ.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2JyV2Wy

Antwort von Prof. Dr. med. Maik Ellies auf den Leserbrief von Jäckel M zu Ellies M. Aus der Gutachtenpraxis: Was ist eine Biopsie mit Inzision? Begutachtung der Kodierung im G-DRG-System in der HNO-Heilkunde. Laryngo-Rhino-Otol 2018; 97: 203–205

10-1055-a-0612-9574-1.jpg

Laryngo-Rhino-Otol 2018; 97: 374-375
DOI: 10.1055/a-0612-9574



© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text



https://ift.tt/2sPS61o

Carcinoma in situ der Stimmlippe

10-1055-a-0588-6611-1.jpg

Laryngo-Rhino-Otol 2018; 97: 377-378
DOI: 10.1055/a-0588-6611



© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text



https://ift.tt/2sZMuAT

Wie würden Sie entscheiden?

10-1055-a-0588-6633-1.jpg

Laryngo-Rhino-Otol 2018; 97: 415-418
DOI: 10.1055/a-0588-6633



© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text



https://ift.tt/2MkuD0w

Das Plattenepithelkarzinom des Naseneingangs – Eine Literaturübersicht

10-1055-a-0592-7965-1.jpg

Laryngo-Rhino-Otol 2018; 97: 379-391
DOI: 10.1055/a-0592-7965

Hintergrund Das Plattenepithelkarzinom des Naseneingangs (Vestibulum nasi) ist eine sehr seltene Tumorentität. In der Konsequenz herrscht bezüglich der Ätiologie, des Stagings und der notwendigen Therapie dieser Tumoren nach wie vor Uneinigkeit. Insbesondere die Mitbehandlung regionaler Lymphknotenstationen ist Gegenstand wissenschaftlicher Diskussionen. Methode Alle via Pubmed gefundenen Artikel zum Thema wurden hinsichtlich folgender Themenschwerpunkte untersucht: Lymphatische Versorgung, Metastasierung, Inzidenz, Prognose, Risikofaktoren (Leder, Nickel, Nikotin, Humane Papillomaviren), Tumorklassifikationssystem (UICC-, AJCC-, Wang-Klassifikation), Therapie des Primärtumors, Therapie regionaler Lymphknoten und Immunhistochemie. Ergebnisse Im vorliegenden Übersichtsartikel wurden 55 Veröffentlichungen ausgewertet. Die Ergebnisse hinsichtlich der untersuchten Aspekte sind in sich inhomogen. Schlussfolgerungen Als Klassifikationssystem wird die Wang-Klassifikation empfohlen. Für die Behandlung kleinerer Tumoren (T1-T2-Wang) kommen operative Resektionen oder Bestrahlungen in Betracht. Größere Tumoren (T3-Wang) sollten reseziert und einer adjuvanten Bestrahlung zugeführt werden. Im Falle einer cT1-cT2cN0-Situation kann – eine dezidierte bildgebende Diagnostik vorausgesetzt – auf eine elektive Therapie der regionalen Lymphknoten verzichtet werden.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2JGLSao

Chirurgie bei Läsionen des Nervus facialis

10-1055-a-0588-6622-1.jpg

Laryngo-Rhino-Otol 2018; 97: 419-434
DOI: 10.1055/a-0588-6622

Ursachen für eine Läsion mit nachfolgender Lähmung des N. facialis sind vielfältig, von der idiopathischen Fazialisparese bis hin zur Destruktion des Nervs durch einen malignen Tumor. Eine Indikation zur chirurgischen Intervention besteht immer dann, wenn die Wahrscheinlichkeit einer spontanen Heilung mit gutem funktionellen Ergebnis gering oder gar nicht vorhanden ist, und eine medikamentöse Behandlung nicht möglich oder auch der chirurgischen Therapie unterlegen ist.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2sPwG4G

Fragen für die Facharztprüfung

10-1055-a-0588-6664-1.jpg

Laryngo-Rhino-Otol 2018; 97: 435-436
DOI: 10.1055/a-0588-6664



© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text



https://ift.tt/2t0Ptt1

Rhinoplastik

10-1055-a-0588-6708-1.jpg

Laryngo-Rhino-Otol 2018; 97: 437-440
DOI: 10.1055/a-0588-6708



© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text



https://ift.tt/2sPRBo2

Kommentar der Schriftleitung

10-1055-a-0588-6578-1.jpg

Laryngo-Rhino-Otol 2018; 97: 367-368
DOI: 10.1055/a-0588-6578



© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text



https://ift.tt/2JyV290

Conceptual Framework for Addressing Residual Atherosclerotic Cardiovascular Disease Risk in the Era of Precision Medicine.

Author: Patel, Kershaw V. MD; Pandey, Ambarish MD, MSCS; de Lemos, James A. MD
Page: 2551-2553


https://ift.tt/2LJj1Dg

Genetic Risk Stratification: Tipping Point for Global Primary Prevention of Coronary Artery Disease.

Author: Roberts, Robert MD
Page: 2554-2556


https://ift.tt/2Jrnrlk

Hemodynamic and Echocardiographic Comparison of the Lotus and CoreValve Transcatheter Aortic Valves in Patients With High and Extreme Surgical Risk: An Analysis From the REPRISE III Randomized Controlled Trial.

Author: Asch, Federico M. MD; Vannan, Mani A. MBBS; Singh, Siddharth MD; Khandheria, Bijoy MD; Little, Stephen H. MD; Allocco, Dominic J. MD, MS; Meredith, Ian T. AM, MBBS, PhD; Feldman, Ted E. MD; Reardon, Michael J. MD; Weissman, Neil J. MD
Page: 2557-2567


https://ift.tt/2LJlmOi

The Lotus Valve: Can It Float Above the Muddy Waters?.

Author: Hahn, Rebecca T. MD
Page: 2568-2571


https://ift.tt/2sPTj8W

Cigarette Smoking and Incident Heart Failure: Insights From the Jackson Heart Study.

Author: Kamimura, Daisuke MD, PhD; Cain, Loretta R. PhD; Mentz, Robert J. MD; White, Wendy B. PhD; Blaha, Michael J. MD, MPH; DeFilippis, Andrew P. MD, MS; Fox, Ervin R. MD, MPH; Rodriguez, Carlos J. MD, MPH; Keith, Rachel J. PhD, NP; Benjamin, Emelia J. MD, ScM; Butler, Javed MD, MPH; Bhatnagar, Aruni PhD; Robertson, Rose M. MD; Winniford, Michael D. MD; Correa, Adolfo MD, MPH, PhD; Hall, Michael E. MD, MS
Page: 2572-2582


https://ift.tt/2HJAjxs

Associations of Fitness, Physical Activity, Strength, and Genetic Risk With Cardiovascular Disease: Longitudinal Analyses in the UK Biobank Study.

Author: Tikkanen, Emmi PhD; Gustafsson, Stefan PhD; Ingelsson, Erik MD, PhD
Page: 2583-2591


https://ift.tt/2Jw0wFB

Inhibition of Endothelial Notch Signaling Impairs Fatty Acid Transport and Leads to Metabolic and Vascular Remodeling of the Adult Heart.

Author: Jabs, Markus PhD; Rose, Adam J. PhD; Lehmann, Lorenz H. MD; Taylor, Jacqueline MSc; Moll, Iris MLS; Sijmonsma, Tjeerd P. BcS; Herberich, Stefanie E. PhD; Sauer, Sven W. PhD; Poschet, Gernot PhD; Federico, Giuseppina PhD; Mogler, Carolin MD; Weis, Eva-Maria MSc; Augustin, Hellmut G. DVM, PhD; Yan, Minhong PhD; Gretz, Norbert MD; Schmid, Roland M. MD; Adams, Ralf H. PhD; Grone, Hermann-Joseph MD; Hell, Rudiger PhD; Okun, Jurgen G. PhD; Backs, Johannes MD; Nawroth, Peter P. MD; Herzig, Stephan PhD; Fischer, Andreas MD
Page: 2592-2608


https://ift.tt/2LEZNi3

Top-NOTCH Regulation of Cardiac Metabolism.

Author: Lim, Radiance PhD; Potente, Michael MD
Page: 2609-2612


https://ift.tt/2sShwLO

Cytosolic DNA Sensing Promotes Macrophage Transformation and Governs Myocardial Ischemic Injury.

Author: Cao, Dian J. MD, PhD; Schiattarella, Gabriele G. MD, PhD; Villalobos, Elisa PhD; Jiang, Nan MSc; May, Herman I. BSc; Li, Tuo PhD; Chen, Zhijian J. PhD; Gillette, Thomas G. PhD; Hill, Joseph A. MD, PhD
Page: 2613-2634


https://ift.tt/2LEZGTF

Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document.

Author: Garcia-Garcia, Hector M. MD; McFadden, Eugene P. MD; Farb, Andrew MD *,; Mehran, Roxana MD; Stone, Gregg W. MD; Spertus, John MD; Onuma, Yoshinobu MD; Morel, Marie-angele BSc; van Es, Gerrit-Anne PhD; Zuckerman, Bram MD *,; Fearon, William F. MD; Taggart, David MD; Kappetein, Arie-Pieter MD; Krucoff, Mitchell W. MD; Vranckx, Pascal MD; Windecker, Stephan MD; Cutlip, Donald MD; Serruys, Patrick W. MD; On behalf of the Academic Research Consortium
Page: 2635-2650


https://ift.tt/2Jw0nlx

Prevalence of Masked Hypertension in Untreated and Treated Patients With Office Blood Pressure Below 130/80 mm Hg.

Author: de la Sierra, Alejandro MD, PhD; Banegas, Jose R. MD, PhD; Vinyoles, Ernest MD, PhD; Segura, Julian MD, PhD; Gorostidi, Manuel MD, PhD; de la Cruz, Juan J. MSc; Ruilope, Luis M. MD, PhD
Page: 2651-2653


https://ift.tt/2HEYwVV

Letter by Del Pinto et al Regarding Article, "Prevention of Stroke With the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)".

Author: Del Pinto, Rita MD; Ferri, Claudio MD; Borghi, Claudio MD
Page: 2654-2655


https://ift.tt/2Jv3KcD

Letter by Thomopoulos and Michalopoulou Regarding Article, "Prevention of Stroke With the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)".

Author: Thomopoulos, Costas MD; Michalopoulou, Helena MD
Page: 2656-2657


https://ift.tt/2HHjvaj

Letter by Cordero et al Regarding Article, "Prevention of Stroke With the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)".

Author: Cordero, Alberto MD, PhD; Bertomeu-Gonzalez, Vicente MD, PhD; Rodriguez-Manero, Moises MD
Page: 2658-2659


https://ift.tt/2sQ8Dm8

Letter by Koh Regarding Article, "Prevention of Stroke With the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)".

Author: Koh, Kwang Kon MD, PhD
Page: 2660-2661


https://ift.tt/2LIspHa

Response by Bohula et al to Letters Regarding Article, "Prevention of Stroke With the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial)".

Author: Bohula, Erin A. MD, DPhil; Wiviott, Stephen D. MD; Giugliano, Robert P. MD, SM; Park, Jeong-Gun PhD; Murphy, Sabina A. MPH; Cannon, Christopher P. MD; Braunwald, Eugene MD
Page: 2662-2663


https://ift.tt/2sOC5Zx

Letter by Stavropoulos et al Regarding Article, "Influence of Baseline Diastolic Blood Pressure on Effects of Intensive Compared With Standard Blood Pressure Control".

Author: Stavropoulos, Konstantinos MD; Imprialos, Konstantinos P. MD; Grassos, Charris MD
Page: 2664-2665


https://ift.tt/2LJl7To

Letter by Rahman and McEvoy Regarding Article, "Influence of Baseline Diastolic Blood Pressure on Effects of Intensive Compared With Standard Blood Pressure Control".

Author: Rahman, Faisal BM BCh; McEvoy, John W. MB, BCh, BAO, MHS
Page: 2666-2667


https://ift.tt/2Jt0KNP

Response by Beddhu et al to Letters Regarding Article, "Influence of Baseline Diastolic Blood Pressure on Effects of Intensive Compared With Standard Blood Pressure Control".

Author: Beddhu, Srinivasan MD; Chertow, Glenn M. MD; Cheung, Alfred K. MD; Cushman, William C. MD; Greene, Tom PhD; Wei, Guo MS; Boucher, Robert BS; Whelton, Paul K. MB, MD, MSc; for the SPRINT Research Group
Page: 2668-2669


https://ift.tt/2LKfQLr

Letter by Madias Regarding Article, "Left Ventricular Hypertrophy Revisited: Cell and Matrix Expansion Have Disease-Specific Relationships".

Author: Madias, John E. MD
Page: 2670-2671


https://ift.tt/2Ju6BT0

Relative importance of wildlife and livestock transmission route of brucellosis in southwestern Uganda

S23523409.gif

Publication date: August 2018
Source:Data in Brief, Volume 19
Author(s): Pius Mbuya Nina, Herwig Leirs, Samuel Mugisha, Patrick Van Damme
The data in brief provides a descriptive summary of the field data collected using Eco-health approach in order to support local effort aimed at creating information base for taking evidence-based decisions, especially in regard to wildlife conservation outside protected area and range resource management. The data were collected between June 2012 and July 2014 on a range of issues including wild animals, livestock, household income and cost of diseases control in cattle. In a nutshell the data article shows spatial pattern of a declining brucellosis prevalence in cattle linked to animal population density with increasing distance away from the Lake Mburo National Park (LMNP) boundary in southwestern Uganda. It is the trend of animal distribution in private land that the pastoralist communities perceived as influencing economic losses associated with diseases affecting cattle production. The pastoralists strongly believe that wild ungulates grazing with cattle outside the park on a daily basis present a potential risk of disease transmission which adversely affects their cherished source of livelihood. This article refers to "Brucellosis in cattle and micro-scale spatial variability of pastoral household income from dairy production in south western Uganda. Acta tropica", Acta Tropica, 2018.



https://ift.tt/2LHwtY1

Running on empty – a nationwide large-scale examination of compulsive exercise in eating disorders

Abstract

Background

Compulsive exercise (CE) has been the neglected "Cinderella" among eating disorder (ED) symptoms, even though it seems to impact severity, treatment and outcome. This prompted a large-scale and systematic examination of the impact of CE in a representative ED sample.

Methods

CE was examined in over 9000 female and male patients from a clinical ED database (covering out-patient, day and/or residential treatment) with respect to prevalence, ED diagnosis, ED symptoms, clinical features, patient characteristics, and outcome at 1-year follow-up. Relationships between changes in CE behavior and remission were also examined.

Results

CE was a transdiagnostic symptom, present in nearly half of all patients (48%). It was associated with greater overall ED pathology, particularly dietary restraint, and negative perfectionism. Initial CE did not impact remission rate, but patients continuing or starting CE during treatment had considerably lower remission rates compared to patients who never engaged in, or ceased with, CE. Results were comparable for females and males.

Conclusions

At baseline, there were few differences between patients with and without CE, except a somewhat higher symptom load for patients with CE, and CE did not predict ED outcome. However, how CE developed during treatment to 1-year follow-up considerably impacted remission rates. We strongly recommend CE to be systematically assessed, addressed, and continuously evaluated in all ED patients seeking treatment.



https://ift.tt/2sYJbKs

Environment, cancer and inequalities—The urgent need for prevention

S09598049.gif

Publication date: Available online 11 June 2018
Source:European Journal of Cancer
Author(s): Paolo Vineis, Daniela Fecht
The proportion of total deaths attributable to environmental factors is estimated to be 23% of global deaths and 22% of global disability-adjusted life years (DALYs) according to one review. These estimates encompass all environmental agents including infectious agents but excluding behavioural factors. The authors of the review also estimated that 16% (95% CI: 7–41%) of cancer deaths are attributable to environmental risk factors (and 36% [95% CI: 17–52%] for lung cancer). In this article, we focus on the reasons why epidemiology is often unable to account for the whole burden of environmental carcinogens. The experience of air pollution is particularly instructive. While in the 1970s and early 1980s, air pollution was considered as a relatively marginal exposure in terms of attributable risks, the most recent estimate is that it accounts for 7.6% of global deaths and 4.2% of global DALYs world-wide (with East and South Asia accounting for 59% of the total). According to a review, ambient fine particulate matter air pollution contributed to 17.1% of ischaemic heart disease, 14.2% of cerebrovascular disease, 16.5% of lung cancer, 24.7% of low respiratory infections, and 27.1% of COPD mortality in 2015. Estimates for cancer as a whole are not available. The change in appreciation of the role of air pollution has been mainly due to the refinement of exposure assessment methods and the new generations of longitudinal studies. Mechanistic evidence via omic technologies is now rapidly increasing, thus lending credibility to previous epidemiological ('black box') associations. Much less is known about other environmental contaminants, some of which are widespread and pervasive, thus suggesting the need for the same rigourous methods as those applied to air pollution. Finally, a crucial issue remains inequality across different population groups, with uneven exposure to hazards and acquired susceptibilities due to multiple concomitant exposures and poorer health status.



https://ift.tt/2LJwCtY

Efficacy and safety of regorafenib compared to placebo and to post-cross-over regorafenib in advanced non-adipocytic soft tissue sarcoma

S09598049.gif

Publication date: August 2018
Source:European Journal of Cancer, Volume 99
Author(s): Thomas Brodowicz, Olivier Mir, Jennifer Wallet, Antoine Italiano, Jean-Yves Blay, François Bertucci, Wolfgang Eisterer, Christine Chevreau, Sophie Piperno-Neumann, Emmanuelle Bompas, Thomas Ryckewaert, Bernadette Liegl-Antzwager, Julien Thery, Nicolas Penel, Axel Le Cesne, Marie-Cécile Le Deley
IntroductionThe placebo-controlled phase-2 REGOSARC trial demonstrated the efficacy of regorafenib in patients with leiomyosarcoma, synovial sarcoma and other non-adipocytic sarcoma but not in liposarcoma. Patients initially allocated to placebo were allowed to receive regorafenib after progression. We report here an updated analysis of the trial including evaluation of regorafenib activity after cross-over.MethodsFrom June 2013 to December 2014, 139 patients were enrolled in the non-adipocytic sarcoma cohorts. Median follow-up is now 32.4 months. Benefit of regorafenib versus placebo in terms of progression-free survival (PFS) and overall survival (OS) from randomisation was estimated by hazard ratio (HR) in Cox models. In the placebo arm, intra-patient benefit of regorafenib after cross-over was evaluated by the growth modulation index (GMI) (GMI was here, for each patient, PFS after cross-over regorafenib divided by PFS with placebo). Furthermore, the activity of delayed (after cross-over) versus early (at study entry) regorafenib was evaluated by comparing PFS after cross-over to regorafenib to PFS after randomisation in the regorafenib arm.ResultsPFS benefit of regorafenib as compared to placebo was confirmed with longer follow-up (HR = 0.50; 95% CI: 0.35–0.71; p < .0001). OS was not statistically significant different (HR = 0.78; 0.54–1.12; p = .18). This finding may partially be explained by the fact that 55/68 patients who progressed on placebo (81%) received cross-over Regorafenib after progression: 59% of them had a GMI ≥ 1.3 (95% CI, 45–71%). Delayed start of regorafenib was associated with a statistically non-significant shorter PFS as compared to early treatment (HR = 1.21; 0.84–1.73; p = .30) without impact on OS.ConclusionsObserved PFS confirms that regorafenib warrants further clinical investigation in refractory non-adipocytic sarcomas.



https://ift.tt/2JNOGpA

Dasatinib sensitises KRAS-mutant cancer cells to mitogen-activated protein kinase kinase inhibitor via inhibition of TAZ activity

S09598049.gif

Publication date: August 2018
Source:European Journal of Cancer, Volume 99
Author(s): Guanhua Rao, In-kyu Kim, Fabio Conforti, Jing Liu, Yu-Wen Zhang, Giuseppe Giaccone
PurposeOncogenic KRAS mutations occur frequently in solid tumours, but no clinically applicable targeted strategy is yet available for treating human cancers with mutant KRAS. Here we aimed to identify a strategy for the treatment of KRAS-driven cancers.Experimental DesignCell viability and colony forming assays were used to assess the in vitro effect of dasatinib and trametinib as single agents or in combination. Western blot was used to analyse the phosphorylated protein and total protein levels. Xenograft models were used to evaluate the in vivo effect of drug combination on KRAS-driven tumour growth.ResultsHere, we report the discovery of a synergistic interaction between dasatinib (ABL and SRC family kinase inhibitor) and the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib in KRAS-mutant cancer cells. We demonstrated that dasatinib enhanced the antitumour effect of trametinib against the KRAS-mutant cancer models both in vitro and in vivo, and the combination resulted in a significant reduction of cytoplasmic and nucleic TAZ protein level, and therefore decreased downstream protein levels of YAP/TAZ signalling pathway. Furthermore, direct knockdown of TAZ by small interfering RNA was able to increase the sensitivity of KRAS-mutant cells to trametinib treatment.ConclusionThese results indicate that dasatinib enhances the antitumour activity of MEK inhibitor through inhibition of TAZ activity and identify dasatinib and trametinib combination as a potential strategy for the treatment of KRAS-driven cancers.



https://ift.tt/2LIGpAD

Standing sentinel during human sleep: Continued evaluation of environmental stimuli in the absence of consciousness

S10538119.gif

Publication date: September 2018
Source:NeuroImage, Volume 178
Author(s): Christine Blume, Renata del Giudice, Malgorzata Wislowska, Dominik P.J. Heib, Manuel Schabus
While it is a well-established finding that subjects' own names (SON) and familiar voices are salient during wakefulness, we here investigated processing of environmental stimuli during sleep including deep N3 and REM sleep. Besides the effects of sleep depth we investigated how sleep-specific EEG patterns (i.e. sleep spindles and slow oscillations [SOs]) relate to stimulus processing. Using 256-channel EEG we studied processing of auditory stimuli by means of event-related oscillatory responses (de-/synchronisation, ERD/ERS) and potentials (ERPs) in N = 17 healthy sleepers. We varied stimulus salience by manipulating subjective (SON vs. unfamiliar name) and paralinguistic emotional relevance (familiar vs. unfamiliar voice, FV/UFV). Results reveal that evaluation of voice familiarity continues during all NREM sleep stages and even REM sleep suggesting a 'sentinel processing mode' of the human brain in the absence of wake-like consciousness. Especially UFV stimuli elicit larger responses in a 1–15 Hz range suggesting they continue being salient. Beyond this, we find that sleep spindles and the negative slope of SOs attenuate information processing. However, unlike previously suggested they do not uniformly inhibit information processing, but inhibition seems to be scaled to stimulus salience.



https://ift.tt/2LJ8ckA

Motives for drinking alcohol and eating palatable foods: An evaluation of shared mechanisms and associations with drinking and binge eating

elsevier-non-solus.png

Publication date: October 2018
Source:Addictive Behaviors, Volume 85
Author(s): Tera L. Fazzino, Amani Raheel, Natalie Peppercorn, Kelsie Forbush, Taylor Kirby, Kenneth J. Sher, Christie Befort
BackgroundYoung adulthood is a high-risk period for heavy drinking and binge eating, both of which can impact weight and lead to obesity. Examining motives for drinking alcohol and eating palatable foods may facilitate a more integrated understanding of these behaviors during the college years. The current study tested whether shared or distinct (i.e., behavior-specific) motivational mechanisms may explain the occurrence of reward-driven drinking and eating in young adults.MethodsA sample of college freshmen (N = 103) stratified by sex, race/ethnicity, and heavy drinking status were selected to participate. Participants completed questionnaires measuring alcohol use, eating behavior, and motives assessed by the Drinking Motives Questionnaire-Revised and Palatable Eating Motives Scale. Confirmatory factor analysis (CFA) tested whether drinking and eating motives were better represented as single latent motives, or two behavior-specific motives. Structural equation modeling (SEM) was used to test the association between motivational factors and behaviors.ResultsBehavior-specific CFA models demonstrated stronger model fit and higher factor loadings than single motive models. SEM models indicated that eating to cope with negative emotions, to enhance positive experiences, to obtain social reinforcement, and to conform with peers were significantly associated with binge eating (p values < .001). Enhancement and social drinking motives were significantly associated with number of weekly drinks (p values < .001).ConclusionsWhile motives for drinking alcohol and eating palatable foods may satisfy common goals, findings suggest motivational mechanisms may be behavior-specific. Enhancement and social motives may be important factors to target in prevention programs for both drinking and binge eating.



https://ift.tt/2JBzGrs

Environmental behaviors of spirotetramat in water

Abstract

Spirotetramat is a pesticide with bidirectional systemicity in both xylem and phloem. Currently, researches show that spirotetramat has definite toxicity to aquatic organism. This paper aims to study the environmental behaviors of spirotetramat in water, in the hope of providing guidance for security evaluation of spirotetramat. The researches in this paper showed that under lighting condition, the half-life period of spirotetramat in water was 13.59 days. In water, spirotetramat could be degraded into B-enol and B-keto. As seen from the residual concentrations of two products, B-enol was the dominant degradation product. Under different temperatures, the hydrolysis products of spirotetramat remain B-enol and B-keto. The temperature has little effect on the residual concentration of spirotetramat in water. The residual concentration of B-enol in water gradually increased with the extension of time but B-keto had no significant change. In the buffer solution of different pH values, the degradation rate of spirotetramat was significantly enhanced with the increase of solution pH value. The hydrolysis products of spirotetramat in buffer solution of different pH values were still B-enol and B-keto, and pH exerted certain influence on the residual concentration of B-enol in water. The hydrolysis conversion of spirotetramat has theoretical and practical significance for the safe and reasonable usage of it, as well as for the further evaluation of spirotetramat's ecological risk in water.



https://ift.tt/2l5oUPP

Effect of anhydrous ethanol/gasoline blends on performance and exhaust emissions of spark-ignited non-road engines

Abstract

Ethanol is a renewable fuel and it is considered an alternative to gasoline in Otto-cycle engines. The present study evaluated the behavior of exhaustion gas carbon monoxide (CO) and total hydrocarbons (THC) according to the levels of anhydrous ethyl alcohol (AEA) added to gasoline in different proportions (E0, E10, E20, E27, that is, pure gasoline and its blends with AEA at 10, 20, and 27% v/v) in the use of non-road single cylinder engines of different powers (13 and 6.5 hp), to the loads applied to engine-generators and the air-fuel ratio (A/F) admitted to the engine cylinders. Also, the performance of engine-generators was verified in terms of mass, specific and energetic consumption and efficiency of the evaluated systems for the same blends and loads. The results showed that an increase in the AEA content in the blend resulted in significant drops in CO and THC concentrations for both engine-generators, while fuel consumption showed a slight upward trend; the increases in applied loads resulted in an increase in CO and THC concentrations and fuel consumption. In general, a higher AEA content (oxygenated) in the blends had a greater effect on gaseous emissions compared to the effect on consumption and system efficiency.



https://ift.tt/2y4i3PL

Testing biomarker feasibility: a case study of Laeonereis culveri (Nereididae, Annelida) exposed to sewage contamination in a subtropical estuary

Abstract

The feasibility of biomarkers to accurately detect pollution in estuaries and coastal areas appears to be overestimated in the scientific literature, and is likely stemming from a bias towards publishing only positive results. Herein, we test the applicability of antioxidant capacity and lipid peroxidation to detect potential in situ sewage impacts on a subtropical estuary. We experimentally assessed variation in malondialdehyde (MDA, an indicator of lipid peroxidation) and total antioxidant capacity against peroxyl radicals (ACAP) through transplantations of the worm Laeonereis culveri from control to sewage-polluted areas. Variations in biomarkers were more related to natural environmental variability and small-scale heterogeneity among areas than to experimental exposure to sewage. Use of oxidative stress biomarkers is promising but further experimental work under real-life conditions is necessary to further validate and establish their accuracy and feasibility for practical purposes.



https://ift.tt/2l4Vph9

Interaction between copper and extracellular nucleic acids in the EPS of unsaturated Pseudomonas putida CZ1 biofilm

Abstract

The role of extracellular DNA (eDNA) in biofilm in heavy metal complexation has been little reported. In this study, the interaction between the extracellular fraction of unsaturated biofilms and Cu2+ was studied using random amplified polymorphic DNA (RAPD) and synchrotron-based X-ray absorption spectroscopy (XAS) analyses. Under Cu2+ stress, the amount of eDNA was about 10-fold higher than the treatment without Cu2+ stress, which was substantially more than the amount of intracellular DNA (iDNA) present in the biofilm. The eDNA content increased significantly under Cu2+ stress and higher eDNA contents were found in colloidal extracellular polymeric substances (EPS) than in capsular EPS in Luria-Bertani medium. It was found that the composition of eDNA was distinctly changed under conditions of Cu2+ stress compared with the treatments without Cu2+ treatments, with specific eDNA bands appearing under Cu2+ treatments as revealed by RAPD analyses. X-ray absorption fine structure (XAFS) analysis assessing the molecular speciation of copper showed that copper in the secreted eDNA mainly existed as species resembling Cu3(PO4)2, followed by Cu-citrate species. This study investigated the interaction between copper and eDNA in unsaturated Pseudomonas putida CZ1 biofilms. Potential function of eDNA in biofilms under Cu2+ stress was found.



https://ift.tt/2t0wVsF

Erratum: Periphere Regionalanästhesie ohne Komplikationen – Ein Traum wird wahr?!

Anästhesiol Intensivmed Notfallmed Schmerzther
DOI: 10.1055/a-0629-0254



Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text



https://ift.tt/2MiqeLC

Erratum: Periphere Regionalanästhesie ohne Komplikationen – Ein Traum wird wahr?!

Anästhesiol Intensivmed Notfallmed Schmerzther
DOI: 10.1055/a-0629-0254



Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text



https://ift.tt/2MiqeLC

The Impact of Alcohol on Breathing Parameters during Sleep: A Systematic Review and Meta-analysis

Alcohol, a muscle relaxant, can potentially worsen obstructive sleep apnea (OSA) but the literature on the effects of alcohol on OSA is conflicting. This systematic review and meta-analysis of randomized controlled trials examined the impact of alcohol on breathing parameters during sleep. Ovid Medline, Embase and PsycINFO databases were queried through November 1, 2017 for studies that reported objective measures of breathing during sleep, prior to and after alcohol administration. Weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated for apnea-hypopnea index (AHI) and mean oxyhemoglobin saturation (SpO2).

https://ift.tt/2HFsF7m

Screening effects of metsulfuron-methyl to collembolans and earthworms: the role of adjuvant addition on ecotoxicity

Abstract

Metsulfuron-methyl is a common active ingredient recommended for use in pre- and post-emergence control of annual grasses and broadleaf weeds in crops, usually applied with mineral oil as adjuvant to enhance its efficiency. Despite the increasing use of this herbicide, there are no information on its ecotoxicity effects to soil fauna. Avoidance and lethality tests were performed with earthworms and collembolans using tropical artificial soil contaminated with formulated products Ally® (600 g L−1 metsulfuron-methyl) and Assist® (756 g L−1 mineral oil) as adjuvant. Lethality test with earthworms showed no difference when tested with or without adjuvant. When Ally® was tested alone, it caused avoidance behavior only at high concentrations (5000 and 10,000 times field predicted dose). However, Assist® addition changed the response of soil invertebrates increasing the avoidance even at field predicted doses. The toxicity of the adjuvant was confirmed in tests exposing collembolans and earthworms to Assist® alone resulting in avoidance behavior. The results clearly show that the addition of mineral oil enhanced the ecotoxicity of metsulfuron-methyl. This study provides an important contribution to the knowledge on the toxicity of metsulfuron-methyl and indicates that adjuvants should be considered in risk assessment of pesticides, considering that under field conditions, these products are applied together.



https://ift.tt/2Miaic0

Chemical composition of rainwater in the Sinos River Basin, Southern Brazil: a source apportionment study

Abstract

This study aimed to assess the chemical composition of the rainwater in three areas of different environmental impact gradients in Southern Brazil using the receptor model EPA Positive Matrix Factorization (EPA PMF 5.0). The samples were collected in a bulk sampler, from October 2012 to August 2014, in three sampling sites along with the Sinos River Basin: Caraá, Taquara, and Campo Bom. The major ions NH4+, Na+, K+, Ca2+, Mg2+, F, Cl, NO3, SO42−, and pH were analyzed, as well as identify the main emission sources. The most abundant cations and anions were Ca2+, Na+, Cl, and SO42−, respectively. The mean pH value in the Sinos River Basin during the study period was 6.07 ± 0.49 (5.13–7.05), which suggests inputs of alkaline species into the atmosphere. The most important neutralizing agents of sulfuric and nitric acids in the Sinos River Basin are Ca2+ (NF = 1.36) and NH4+ (NF = 0.57). The source apportionment provided by the EPA PMF 5.0 resulted in four factors, which demonstrate the influence of anthropogenic and natural sources, in the form of (a) industry/combustion of fossil fuels (F and SO42−), (b) marine contribution (Na+ and Cl), (c) crustal contribution (K+, Ca2+, and NO3), and (d) agriculture/livestock (NH4+). Therefore, this study allows a more appropriate understanding of factors that contribute to rainwater chemical composition and also to possible changes in air quality.



https://ift.tt/2t0pAto

Low-thermal remediation of mercury-contaminated soil and cultivation of treated soil

Abstract

In this study, low-thermal technology was used to treat the mercury contaminated farmland soil from a chemical plant in Guizhou Province, China. A series of field planting experiments were also aimed at determining the content of total and methyl-Hg in crop plants after thermal treatment. The results showed that the mercury concentration in soils was reduced about 70% from 255.74 mg/kg to 80.63 mg/kg when treated at 350 °C for 30 min in engineering-scale experiments, and the treated soil retained most of its original soil. Organic-bound and residual mercury in treated soil were reduced by 64.1 and 56.4% by means of a sequential extraction procedure, respectively. The total and methyl-mercury concentrations in crops decreased significantly, and the degree of soil mercury accumulation to crop roots has been reduced significantly. The total Hg concentrations in potato and corn were lower than the mercury tolerance limits for food in China, and the Hg concentration of radish was close to the limit. The technology provides a more sustainable remediation method for treating mercury-contaminated farmland soil in future engineering applications.



https://ift.tt/2sQM7t6

Reduced arsenic availability and plant uptake and improved soil microbial diversity through combined addition of ferrihydrite and Trichoderma asperellum SM-12F1

Abstract

Arsenic (As) accumulation in agricultural soils is prone to crop uptake, posing risk to human health. Passivation shows potential to inactivate soil labile As and lower crop As uptake but often contributes little to improving the microbiota in As-contaminated soils. Here, the combined addition of ferrihydrite and Trichoderma asperellum SM-12F1 as a potential future application for remediation of As-contaminated soil was studied via pot experiments. The results indicated that, compared with the control treatment, the combined addition of ferrihydrite and T. asperellum SM-12F1 significantly increased water spinach shoot and root biomass by 134 and 138%, respectively, and lowered As content in shoot and root by 37 and 34%, respectively. Soil available As decreased by 40% after the combined addition. The variances in soil pH and As fractionation and speciation were responsible for the changes in soil As availability. Importantly, the combined addition greatly increased the total phospholipid fatty acids (PLFAs) and gram-positive (G+), gram-negative (G−), actinobacterial, bacterial, fungal PLFAs by 114, 68, 276, 292, 133, and 626%, respectively, compared with the control treatment. Correspondingly, the soil enzyme activities closely associated with carbon, nitrogen, and phosphorus mineralization and antioxidant activity were improved. The combination of ferrihydrite and T. asperellum SM-12F1 in soils did not reduce their independent effects.



https://ift.tt/2JEGRPI

A comparison of the International Association of Diabetes and Pregnancy Study Groups Recommendations with Former Criteria for Diagnosing Gestational Diabetes Mellitus: A Retrospective Cohort Study

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0630-5118

Aim The aim of the study was to compare the frequency of gestational diabetes mellitus (GDM) and pregnancy outcomes in women diagnosed by WHO 1999 and IADPSG criteria. Methods This was a retrospective cohort study comprising 1508 women who underwent a 75-g OGTT after the 24th week of gestation at the University Hospital of Bialystok between 2004 and 2012. Results GDM was diagnosed by WHO 1999 criteria in 486 (32.2%) patients and by IADPSG criteria in 397 (26.3%) women. Three hundred fifty five (23.5%) patients fulfilled both criteria, whereas 111 (7.4%) and 39 (2.6%) subjects met only WHO 1999 or IADPSG criteria, respectively. Isolated fasting hyperglycemia was found in 3.4% of patients fulfilling WHO 1999 criteria and in 17.6% of women who met IADPSG criteria. In total, fasting glycemic value was diagnostic in 42.8% of the participants fulfilling the new criteria. The main risk factor for GDM was family history of diabetes (OR 2.285 [95%CI: 1.772-2.945], p=0.00001). The rates of cesarean section and macrosomia were higher in the group with GDM than in the healthy women (54.7% vs 41.9% and 18.9% vs 13.9%, respectively), but the differences were not significant. Three months postpartum the disturbances of glucose tolerance were found in 21% of the patients with GDM. Conclusions The introduction of the IADPS criteria did not increase the prevalence of GDM, but increased the number of patients with fasting hyperglycemia. Twelve weeks postpartum the patients with prior GDM had significantly higher post-load glucose levels than the healthy women.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2MkM29x

Expression of TIGIT and FCRL3 is Altered in T Cells from Patients with Distinct Patterns of Chronic Autoimmune Thyroiditis

11-2017-0434-endo_10-1055-a-0597-8948-1.

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0597-8948

Background Co-inhibitory receptors (IR), such as TIGIT and FCRL3, provide a checkpoint against highly destructive immune responses. Co-expression of TIGIT and FCRL3, in particular, has been linked to the HELIOS+ subset of regulatory CD4+FOXP3+T-cells. Of these, CD4+FOXP3-exon(E)2+ cells have higher expression of IR and exhibit strongest suppressive properties. Nevertheless, how the expression of TIGIT, FCRL3, HELIOS, and FOXP3E2 is regulated in chronic autoimmune thyroiditis (AT), is not known. Methods Thirty patients with AT [encompassing spontaneously euthyroid (euAT), hypothyroid-untreated and L-thyroxine-treated cases)] and 10 healthy controls (HC) were recruited. FCRL3, TIGIT, HELIOS and FOXP3E2 mRNA expression levels in peripheral blood (PB) T cells were measured via quantitative real-time PCR and compared to clinicopathological factors. Results The TIGIT and FCRL3 expression levels from T cells of AT cases were inversely related to the thyroid volume, and were significantly increased in hypothyroid patients (on+off L-thyroxine), but not euAT cases. The FCRL3 expression in PB T cells positively correlated with thyroid-peroxidase autoantibody levels; by contrast, T cells from aged AT patients and combined samples (AT+HC) accumulated more TIGIT mRNA. The patients with higher TIGIT mRNA levels had a greater prevalence of hypothyroidism, showing higher peak thyrotropin levels at diagnosis or at follow-up. Conclusions Multiple IR, namely FCRL3 and TIGIT, but not the transcription factors HELIOS and FOXP3E2, showed increased mRNA levels in PB T cells from end-stage, long-standing and/or more aggressive AT, in proportion to disease severity. A relation with major clinical subphenotypes was observed, thereby identifying IR as potentially important players in AT.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2JFSVQH

The Role of Different Molecular Markers in Papillary Thyroid Cancer Patients with Acromegaly

01-2018-0045-endo_10-1055-a-0629-9223-1.

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0629-9223

Purpose Prevalence of papillary thyroid cancer (PTC) is increased in patients with acromegaly. We aimed to determine the protein expression of BRAF, RAS, RET, insulin like growth factor 1(IGF1), Galectine 3, CD56 in patients with PTC related acromegaly and to compare the extensity of these expressions with normal PTC patients and benign thyroid nodules. Methods We studied 313 patients with acromegaly followed in Cerrahpasa Medical Faculty, Endocrinology and Metabolism Clinic between 1998 and 2015. On the basis of availability of pathological specimen of thyroid tissues, thyroid samples of 13 patients from 19 with acromegaly related PTC (APTC), 20 normal PTC and 20 patients with multinodulary goiter (MNG) were histopathologically evaluated. Protein expressions were determined via immunohistochemical staining in ex-vivo tumor samples and benign nodules. Results The incidence of PTC in acromegaly patients were 6% (n=19). Among patients with PTC, APTC and MNG, all the immunohistochemical protein expressions we have studied were higher in papillary thyroid cancer groups (p<0.01, for all). Between PTC group without acromegaly and APTC, galectin 3 and IGF1 expression was significantly higher in acromegalic patients (p<0.01 for all) while RAS was predominantly higher in PTC patients without acromegaly (p<0.01). Conclusion BRAF expression was not higher in PTC with acromegaly patients compared to PTC patients without acromegaly. Galectine 3 and IGF1 were expressed more intensively in APTC. These positive protein expressions may have more influence on determining malign nodules among acromegaly patients.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2JsWoWV

Assessment of the Dynamic Insulin Secretion and Sensitivity Test (DISST) Pre and Post Gastric bypass Surgery

11-2017-0441-dia_10-1055-a-0603-3539-1.j

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0603-3539

Objective To compare the dynamic insulin secretion and sensitivity test (DISST) with the euglycaemic clamp in individuals undergoing open Roux-en-Y gastric bypass (RYGB) surgery prior-to and one month after surgery. Methods Insulin sensitivity in individuals with obesity undergoing RYGB was studied with DISST and a euglycaemic hyperinsulinaemic clamp. Results Eleven participants, including nine females, mean(SD) age 51.2(12.1)yrs, with a preoperative BMI of 48.7(9.5)kg/m2 were studied. Weight reduced from a mean(SD) of 133.8(29.8)kg to 123.8(28.9)kg post-surgery (p<0.001). The mean(SD) insulin sensitivity index (ISI-DISST) was 3.07×10−4(2.18)L.pmol−1.min−1 preoperatively and 2.36 ×10−4(0.78)L.pmol−1.min−1 postoperatively (p=0.37). The mean(SD) clamp ISI was 2.14 ×10−2(1.80)mg.L.kg−1.min−1.pmol−1 and 2.00×10−2.(0.76)mg.L.kg−1.min−1.pmol−1 postoperatively (p=0.86). Correlation between ISI-DISST and ISI-Clamp preoperatively was r=0.81(95%CI 0.37-0.95) and post-operatively r=0.47(95%CI 0-0.88). Bland-Altman analysis demonstrates systematic bias between the two tests, where DISST underestimated insulin sensitivity compared with the clamp by 0.96×10-2.mg.L.kg−1.min−1.pmol−1 (95%CI -2.24 to 0.32). Conclusions There was a strong correlation between DISST and the clamp preoperatively and DISST can be used to estimate insulin sensitivity in individuals with morbid obesity. After RYGB surgery, DISST had a weaker correlation with the clamp suggesting the fundamental physiological determinants of insulin sensitivity being measured by each method change in different ways with changes in glucose homeostasis following RYGB surgery.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2JCW8Ra

Increased OGA Expression and Activity in Leukocytes from Patients with Diabetes: Correlation with Inflammation Markers

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0596-7337

O-linked-β-N-Acetylglucosaminylation (O-GlcNAcylation), a reversible post-translational modification involved in diabetic complications, is regulated by only two enzymes, O-linked N-acetylglucosamine transferase (OGT) and β-N-Acetylglucosaminidase (OGA). Increased OGA expression has been described previously in blood cells from patients with diabetes and was interpreted as an adaptative response to hyperglycemia-induced O-GlcNAcylation. OGA expression was thus proposed to have potential utility as a diagnostic marker. The present work was undertaken to determine whether determination of OGA enzymatic activity in blood cells could constitute a more rapidly accessible marker than OGA expression level measurements.Blood samples were obtained from patients with type 2 diabetes from the Department of Diabetology of the Cochin Hospital and healthy volunteers from the French blood Agency. OGA enzymatic activity and OGA mRNA expression levels were evaluated in leucocytes from patients with type 2 diabetes and from healthy donors.OGA activity was higher in leucocytes from patients with diabetes compared to control individuals. Surprisingly, OGA activity was not correlated hyperglycaemia markers (blood glucose, fructosamine, HbA1c) but was positively correlated with the inflammatory marker C-reactive protein. OGA mRNA levels were also increased in leucocytes from patients with diabetes and were correlated with mRNA coding for two pro-inflammatory proteins, TNFα and TxNIP.Therefore, OGA activity in leucocytes might be a more easily accessible biomarker than OGA expression levels. However, changes in OGA activity observed in patients with type 2 diabetes may reflect the inflammatory rather than the glycaemic status of these patients.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2Mkgu3q

A Novel c.125 T>G (p.Val42Gly) Mutation in The Human INS Gene Leads to Neonatal Diabetes Mellitus via a Decrease in Insulin Synthesis

11-2017-0437-dia_10-1055-a-0603-3463-1.j

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0603-3463

Background Neonatal diabetes mellitus is likely caused by monogenic mutations, several of which have been identified. INS mutations have a broad spectrum of clinical presentations, ranging from severe neonatal onset to mild adult onset, which suggests that the products of different mutant INS alleles behave differently and utilize distinct mechanisms to induce diabetes. In this study, a neonatal diabetes mellitus patient's INS gene was sequenced, and functional experiments were conducted. Methods The neonatal diabetes mellitus patient's genomic DNA was extracted, and the patient's KCNJ11, ABCC8, and INS genes were sequenced. A novel mutation was identified in INS, and the open reading frame of this human mutant INS gene was inserted into the pMSCV-PIG plasmid. The constructed pMSCV-PIG plasmid was combined with VSV-g and Gag-pol and transfected into 293T cells to package the lentivirus. To stably overexpress the mutant gene, INS-1 cells were infected with the virus. The levels of insulin in the cell culture medium and cytoplasm were determined by ELISA and immunocytochemistry, respectively. Results A heterozygous mutation, c.125T>G (p. Val42Gly), was identified in a neonatal diabetes mellitus patient's INS gene. The human mutant INS open reading frame was overexpressed in INS-1 cells, and the mutant insulin was undetectable in the cell culture medium and cytoplasm. Conclusions The novel heterozygous activating mutation c.125 T>G (p.Val42Gly) impairs the synthesis of insulin by pancreatic beta cells, resulting in diabetes.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2y3Z5ci

Altered microRNA expression during Impaired Glucose Tolerance and High-fat Diet Feeding

02-2018-0078-dia_10-1055-a-0619-4576-1.j

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0619-4576

Objective MicroRNAs (miRNAs) play a critical role in metabolic regulation. Recently, we identified novel miRNAs in the whole blood of South African women of mixed ethnic ancestry. The aim of this study was to investigate whether five of these novel miRNAs are expressed in serum and whether their expression is altered during metabolic dysregulation. Methods Expression levels of the five novel miRNAs (MYN08, MYNO22, MYN059, MYNO66 and MYNO95) were measured in the serum of women with Impaired Glucose Tolerance (IGT) and Normoglycemia (NGT) (n=24), and in the whole blood of vervet monkeys fed a high-fat or standard diet (n=16) using quantitative real-time PCR. Results Only three of the selected novel miRNAs (MYNO8, MYNO22 and MYNO66) were expressed in serum. The expression of MYN08 and MYNO22 were associated with fasting glucose and insulin concentrations, decreased during IGT and able to predict IGT. The expression of these miRNAs were similarly decreased in vervet monkeys fed a high-fat diet. In silico analysis identified a total of 291 putative messenger RNA targets for MYNO8 and MYNO22, including genes involved in gluconeogenesis, carbohydrate metabolism, glucose homeostasis and lipid transport. Conclusion Two novel miRNAs, MYNO8 and MYNO22, are associated with metabolic dysregulation in South African women of mixed ethnic ancestry and with high-fat diet feeding in vervet monkeys. Furthermore, putative gene targets were enriched in biological processes involved in key aspects of glucose regulation, which strengthens the candidacy of these miRNAs as biomarkers for dysglycemia, and warranting further studies to assess their clinical applicability.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2JsWq0Z

Pleiotropic Effect of Lipoprotein-Apheresis on the Soluble Form of Activated Leukocyte Cell Adhesion Molecule (sALCAM) in Familial Hypercholesterolaemia

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0630-0232

Introduction/Background Atherosclerosis is an inflammatory disorder in which several converging immune responses modulate and induce lipid accumulation in macrophages. Activated leukocyte cell adhesion molecule (ALCAM) has been described as a structural homologue of HDL-receptor and functions as a pattern recognition receptor (PRR), while its soluble form sALCAM is involved in ALCAM-dependent and -independent immune mechanisms. The aim of this study was to investigate the effect of aggressive removal of low density lipoprotein-cholesterol (LDL-C) and lipoprotein(a) (Lp [a]) by lipoprotein-apheresis (LA) on sALCAM and blood viscosity as well as to evaluate its association with lipoproteins and serum markers of inflammation.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2JCVVNS

Transcriptomic Analysis of the Association Between Diabetes Mellitus and Myocardial Infarction

02-2018-0047-dia_10-1055-a-0619-4412-1.j

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0619-4412

Background Diabetes mellitus (DM) is a major risk factor for coronary artery disease (CAD), and the complications of CAD are the leading cause of deaths among people with DM. Herein, this study aims to identify the common genes and pathways between diabetes and myocardial infarction (MI) to provide more clues for the related mechanism studies. Methods Differentially expressed genes (DEGs) were identified using the cutoff (|log2(fold change)|>0.45 and P value<0.05) by the analysis of online datasets (GSE9006 and GSE48060) related to DM and MI respectively. Moreover, the overlapped DEGs between DM and MI were identified, followed by enriched Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. And the independent patient RNA samples were collected for qRT-PCR validation of the mRNA expression of these overlapped genes. Results PI3, ACSL1, MMD and MMP were altered in both T1DM and MI, and they were highly related to "regulation of cellular protein metabolic process". Meanwhile, six genes were identified in both T2DM and MI, which are ADM, NFIL3, PI3, SLPI, ACSL1 and MMP9 and significantly related to "negative regulation of endopeptidase activity". And the expression of these genes were validated. Conclusions In summary, we identified the common DEGs and pathways between T1DM or T2DM and MI, and further validated the changes of those DEGs, providing some clues for mechanism study and potentially therapeutic targets.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2Jw202H

Klotho Restraining Egr1/TLR4/mTOR Axis to Reducing the Expression of Fibrosis and Inflammatory Cytokines in High Glucose Cultured Rat Mesangial Cells

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0044-101601

Anti-aging protein Klotho is closely associated with a variety of chronic diseases and age-related diseases. And Klotho gene deficiency enhances the phosphorylation of mammalian target of rapamycin (mTOR), resulting in exacerbating streptozotocin-stimulated diabetic glomerular injury and promoting the progression of early diabetic kidney disease (DKD). However, it has not yet been elucidated that the mechanism of Klotho function on the pathogenesis of diabetic glomerular injury. What's more, insulin represents the antilipolytic effect via the mTOR-early growth response factor 1 (Egr1) regulatory axis in mammalian organism. Valsartan reduced the high glucose-activated toll like report 4 (TLR4) expression and inflammatory cytokines via inhibiting Egr1 expression. In this study, we aim to explore the effects of Klotho on Egr1 expression and TLR4/mTOR pathways activity in high glucose cultured rat mesangial cells (RMCs) in vitro. Our study revealed that high glucose upregulated Egr1 to aggravate the inflammation and fibrosis in RMCs. And high glucose activates Egr1/TLR4/mTOR regulatory axis in MCs, indicating that one coherent feedforward loop is formed. Anti-aging protein Klotho may attenuate glomerular inflammation and fibrosis to provide protection against diabetic kidney injury via inhibiting the activity of Egr1/TLR4/mTOR regulatory axis in high glucose conditions. This study complements the function mechanism of Egr1/TLR4/mTOR regulatory axis playing in the pathogenesis of DKD, and provides a new direction and theoretical basis for anti-aging protein Klotho in DKD treatment.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2y3r0cc

Infected Diabetic Foot Ulcers: No Laterality?

12-2017-0481-dia_10-1055-a-0584-6396-1.j

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0584-6396



© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text



https://ift.tt/2MilJkc

The Effect of the Oral Administration of Leucine on Endothelial Function, Glucose and Insulin Concentrations in Healthy Subjects

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0597-8985

Objective The aim of our study was to investigate the potential differential effect of hyperglycaemia and hyperinsulinaemia induced by glucose infusion alone and in combination with leucine consumption on endothelial function in healthy individuals. Methods Ten male volunteers were examined in random order twice. In one visit, they consumed 250 ml water (baseline) and 30 min later glucose was infused iv. In the other visit, they consumed 250 ml water with 25 g of leucine and 30 min later the same amount of glucose was infused. Serum glucose and insulin were measured at baseline and every 10 min after glucose infusion for 1 h. Endothelial function was evaluated by measurement of flow mediated vasodilatation (FMD) at baseline, 10 and 60 min after glucose infusion. Results In both visits, glucose levels increased to the same degree, whereas insulin response was significantly higher after leucine administration. FMD values declined significantly compared to baseline 10 min after glucose infusion in the control visit (6.9±2.7 vs. 3.2±3.5%, respectively, p=0.006), while no significant change was observed when glucose infusion was followed by leucine consumption. Conclusions Acute hyperglycaemia impairs endothelial function in healthy male individuals. Leucine administration prevents hyperglycaemia-mediated endothelial dysfunction probably due to enhanced insulin secretion.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2JFSuG3

The Effect of Metformin Therapy for Preventing Gestational Diabetes Mellitus in Women with Polycystic Ovary Syndrome: A Meta-Analysis

11-2017-0430-dia_10-1055-a-0603-3394-1.j

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0603-3394

Objective This study was to analyze the efficacy of metformin intervention in preventing gestational diabetes mellitus (GDM). Methods A systematic review and meta-analysis of clinical trials or observational studies of metformin intervention in preventing symptoms of GDM during pregnancy were performed. Medline, Embase, and Cochrane Library were searched through to now. The main evaluated primary outcomes were incident of GDM, miscarriage, preterm delivery, and neonatal mortality. The evaluated secondary outcomes were mean difference of gestational age at birth and birth weight between metformin group and control group. Results We included 6 studies including 3 randomized clinical trials (RCTs), 2 observational studies, and 1 non-RCT in our meta-analysis. A total of 643 patients were enrolled for a follow-up study with continued metformin therapy (n=341) or not (n=302) during pregnancy. Metformin therapy reduced the proportion of patients developing GDM (log Odds Ratio: -1.27; 95%CI: -2.24 to -0.30) but had no significant effect on reducing the proportion of abortion, preterm delivery, and neonatal death in pregnant women with polycystic ovary syndrome (PCOS). Also, it did not cause a significant difference in gestational age at birth and birth weight in metformin group versus control/placebo group. Conclusions Metformin was associated with less frequent GDM development than control diets, suggesting that it is the appropriate intervention to be prescribed to prevent GDM in patients with PCOS.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2JtRPf0

Long Non-Coding RNA CASC2 Improves Diabetic Nephropathy by Inhibiting JNK Pathway

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0629-9958

It's known that long non-coding RNA CASC2 overexpression inhibit the JNK pathway in some disease models, while JNK pathway activation exacerbates diabetic nephropathy. Therefore we speculate that long non-coding RNA CASC2 can improve diabetic nephropathy by inhibiting JNK pathway. Thus, our study was carried out to investigate the involvement of CASC2 in diabetic nephropathy. We found that serum level of CASC2 was significantly lower in diabetic nephropathy patients than in normal people, and serum level of CASC2 showed no significant correlations with age, gender, alcohol consumption and smoking habits, but was correlated with course of disease. ROC curve analysis showed that serum level of CASC2 could be used to accurately predict diabetic nephropathy. Diabetes mellitus has many complications. This study also included a series of complications of diabetes, such as diabetic retinopathy, diabetic ketoacidosis, diabetic foot infections and diabetic cardiopathy, while serum level of CASC2 was specifically reduced in diabetic nephropathy. CASC2 expression level decreased, while JNK1 phosphorylation level increased in mouse podocyte cells treated with high glucose. CASC2 overexpression inhibited apoptosis of podocyte cells and reduced phosphorylation level of JNK1. We conclude that long non-coding RNA CASC2 may improve diabetic nephropathy by inhibiting JNK pathway.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



https://ift.tt/2y3YSpw

Αρχειοθήκη ιστολογίου