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

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Τετάρτη 29 Ιουνίου 2016

A Systematic Review of Unmet Information and Psychosocial Support Needs of Adults Diagnosed with Thyroid Cancer.

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A Systematic Review of Unmet Information and Psychosocial Support Needs of Adults Diagnosed with Thyroid Cancer.

Thyroid. 2016 Jun 27;

Authors: Hyun YG, Alhashemi A, Fazelzad R, Goldberg AS, Goldstein DP, Sawka AM

Abstract
BACKGROUND: Patient education and psychosocial support to patients are important elements of comprehensive cancer care but the needs of thyroid cancer survivors are not well understood.
METHODS: We systematically reviewed the published English-language, quantitative literature on: a) unmet medical information and, b) psychosocial support needs of thyroid cancer survivors. A librarian information specialist searched 7 electronic databases and a hand search was conducted. Two reviewers independently screened citations from the electronic search and reviewed relevant full-text papers. There was consensus between reviewers on the included papers and duplicate independent abstraction was performed. The results were summarized descriptively.
RESULTS: We screened 1984 unique electronic citations and reviewed 51 full-text papers (3 from the hand search). We included 7 cross-sectional, single-arm, survey studies, including data from 6215 thyroid cancer survivor respondents. The respective study sizes ranged from 57 to 2398 subjects. All of the studies had some methodologic limitations. Unmet information needs were variable relating to the disease, diagnostic tests, treatments, and co-ordination of medical care. There were relatively high unmet information needs related to aftercare (especially long-term effects of the disease or its treatment and its management) and psychosocial concerns (including practical and financial matters). Psychosocial support needs were incompletely met. Patient information on complementary and alternative medicine was very limited.
CONCLUSIONS: In conclusion, thyroid cancer survivors perceive many unmet information needs and these needs extend to aftercare. Psychosocial information and supportive care needs may be insufficiently met in this population. More work is needed to improve knowledge translation and psychosocial support for thyroid cancer survivors.

PMID: 27350421 [PubMed - as supplied by publisher]



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Single Center Experience with Potassium-titanyl phosphate (KTP) laser for superficial cutaneous vascular lesions in face.

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Single Center Experience with Potassium-titanyl phosphate (KTP) laser for superficial cutaneous vascular lesions in face.

J Cosmet Laser Ther. 2016 Jun 28;:1-17

Authors: Solak B, Dikicier BS, Kara RO, Erdem T

Abstract
BACKGROUND AND OBJECTIVES: Superficial cutaneous vascular lesions (SCVL) are quite common. Several types of lasers have been used to treat these lesions; however, there are no dedicated treatment guidelines and few studies in the literature addressed their treatment.
AIMS: In this paper we aimed to report our clinical experience with Potassium-titanyl phosphate KTP laser treatment on different types of facial SCVLs including telangiectasia, spider angioma and erythema.
METHODS: Data were retrospectively collected from 146 patients with SCVLs who had been treated with the 532-nm wavelength laser at our outpatient dermatology clinic. Treatment responses were graded as four groups; clearance (>75% improvement compared with the previous session), marked improvement (50-75%), partial improvement (25-50%), and no response (<25%).
RESULTS: The rate of clearance plus marked improvement (favorable outcome) was 66.1% for telangiectasia group, 93.5% for spider angioma group and 26.7% for erythema group. Mean number of treatments was 2.9 ± 1.4 for telangiectasia group, 1.4 ± 0.8 for spider angioma group, and 2.9 ± 1.7 for facial erythema group. Only minimal adverse effects related to treatment procedure were detected in 5 out of 146 (3.4%) patients.
CONCLUSIONS: Our results demonstrated that KTP laser may be a safe and effective laser modality for superficial cutaneous vascular lesions which may be associated with physiological problems due to cosmetic concerns.

PMID: 27351074 [PubMed - as supplied by publisher]



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Predictive toxicology today: the transition from biological knowledge to practicable models.

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Predictive toxicology today: the transition from biological knowledge to practicable models.

Expert Opin Drug Metab Toxicol. 2016 Jun 28;

Authors: Benigni R

PMID: 27351633 [PubMed - as supplied by publisher]



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Thromboxane A2 Regulates CXCL1 and CXCL8 Chemokine Expression in the Nasal Mucosa-Derived Fibroblasts of Chronic Rhinosinusitis Patients.

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Thromboxane A2 Regulates CXCL1 and CXCL8 Chemokine Expression in the Nasal Mucosa-Derived Fibroblasts of Chronic Rhinosinusitis Patients.

PLoS One. 2016;11(6):e0158438

Authors: Tsai YJ, Hao SP, Chen CL, Wu WB

Abstract
BACKGROUND: Chronic rhinosinusitis without nasal polyps (CRSsNP) is a common chronic disease and the etiology remains unclear. Thromboxane A2 (TXA2) participates in platelet aggregation and tissue inflammation. In this study, the CXCL1/8 chemokine and TXA2-TP receptor expression in the CRSsNP mucosa was investigated.
EXPERIMENTAL APPROACH: Immunohistochemistry, chemokine release assay by ELISA, RT-PCR, Real-time PCR, Western blotting, pharmacological and siRNA knockdown analysis were applied in the CRSsNP tissue specimen and cultured nasal mucosa-derived fibroblasts.
RESULTS: The immunohistochemistry results indicated that CXCL1 and CXCL8 were highly expressed in the CRSsNP mucosa compared with the controls; however, the TP receptors were expressed in both mucosa. Therefore, U46619 and IBOP, a TXA2 analog and TP agonist, were used to explore the role of TP activation in CXCL1/8 expression; both of these induced CXCL1/8 mRNA and protein expression in CRSsNP mucosa-derived fibroblasts. U46619 phosphorylated PI-3K, cyclic AMP (cAMP)/PKA, PKC, and cAMP response element (CREB). Activation of cAMP/PKA, PKC, and CREB was the major pathway for cxcl1/8 gene transcription. Pharmacological and siRNA knockdown analyses revealed that activation of cAMP/PKA and PKCμ/PKD pathways were required for CREB phosphorylation and PKA/C crosstalked with the PI-3K pathway.
CONCLUSION AND IMPLICATIONS: Our study provides the first evidence for abundant TP receptor and CXCL1/8 expression in human CRSsNP mucosa and for TXA2 stimulation inducing CXCL1/8 expression in nasal fibroblasts primarily through TP receptor, cAMP/PKA, PKCμ/PKD, and CREB-related pathways.

PMID: 27351369 [PubMed - as supplied by publisher]



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Identification of miRNA/mRNA-Negative Regulation Pairs in Nasopharyngeal Carcinoma.

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Identification of miRNA/mRNA-Negative Regulation Pairs in Nasopharyngeal Carcinoma.

Med Sci Monit. 2016;22:2215-34

Authors: Liu M, Zhu K, Qian X, Li W

Abstract
BACKGROUND Nasopharyngeal carcinoma (NPC) is a common malignancy in South-East Asia. NPC is characterized by distant metastasis and poor prognosis. The pathophysiological mechanism of nasopharyngeal carcinoma is unknown. This study aimed to identify the crucial miRNAs in nasopharyngeal carcinoma and their target genes, and to discover the potential mechanism of nasopharyngeal carcinoma development. MATERIAL AND METHODS Microarray expression profiling of miRNA and mRNA from the Gene Expression Omnibus database was downloaded, and we performed a significance analysis of differential expression. An interaction network of miRNAs and target genes was constructed. The underlying function of differentially expressed genes was predicted through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. To validate the microarray analysis data, significantly different expression levels of miRNAs and target genes were validated by quantitative real-time polymerase chain reaction. RESULTS We identified 27 differentially expressed miRNAs and 982 differentially expressed mRNAs between NPC and normal control tissues. 12 miRNAs and 547 mRNAs were up-regulated and 15 miRNAs and 435 mRNAs were down-regulated in NPC samples. We found a total of 1185 negative correlation pairs between miRNA and mRNA. Differentially expressed target genes were significantly enriched in pathways in cancer, cell cycle, and cytokine-cytokine receptor interaction signaling pathways. Significantly differentially expressed miRNAs and genes, such as hsa-miR-205, hsa-miR-18b, hsa-miR-632, hsa-miR-130a, hsa-miR-34b, PIGR, SMPD3, CD22, DTX4, and CDC6, may play essential roles in the development of nasopharyngeal carcinoma. CONCLUSIONS hsa-miR-205, hsa-miR-18b, hsa-miR-632, hsa-miR-130a, and hsa-miR-34b may be related to the development of nasopharyngeal carcinoma by regulating the genes involved in pathways in cancer and cell cycle signaling pathways.

PMID: 27350400 [PubMed - in process]



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A Mass Involving the Buccal Branch of the Facial Nerve.

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A Mass Involving the Buccal Branch of the Facial Nerve.

JAMA Otolaryngol Head Neck Surg. 2016 Feb;142(2):187-8

Authors: De Mol A, Sciot R, Politis C

PMID: 26719906 [PubMed - indexed for MEDLINE]



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Combined Orofacial Aspergillosis and Mucormycosis: Fatal Complication of a Recurrent Paediatric Glioma-Case Report and Review of Literature.

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Combined Orofacial Aspergillosis and Mucormycosis: Fatal Complication of a Recurrent Paediatric Glioma-Case Report and Review of Literature.

Mycopathologia. 2016 Jun 27;

Authors: Chermetz M, Gobbo M, Rupel K, Ottaviani G, Tirelli G, Bussani R, Luzzati R, Di Lenarda R, Biasotto M

Abstract
Mucormycosis and aspergillosis are two opportunistic fungal infections, which can evolve into life-threatening complications. They generally affect patients with relevant risk factors such as immunocompromisation or long-term use of antibiotics or corticosteroids. Treatment usually combines medical and surgical approaches, often including extended necrosectomies, although the prognosis of generalized fungal infections is very poor. In this paper, we present the case of a 17-year-old girl affected by combined aspergillosis and mucormycosis, following treatment of a recurrent glioma. The patient was hospitalized for a suspected cellulitis of the right hemi-face, involving frontal maxillary area and the upper airways and was immediately put on intravenous antibiotic therapies; after performing nasal septum and maxillary biopsies, concomitant mucormycosis and aspergillosis were diagnosed and antimycotic therapy with liposomal B-amphotericin was administered. After evaluation by the oral surgeon and otolaryngologist, surgical cranio-facial necrosectomy was suggested, but refused by the parents of the patient. The girl died only few days later, due to a respiratory arrest. Awareness of this pathology with prompt diagnosis and early treatment may improve the outcome of these infections and reduce the mortality.

PMID: 27350324 [PubMed - as supplied by publisher]



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The association between obstructive sleep apnea and metabolic syndrome: a systematic review and meta-analysis.

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The association between obstructive sleep apnea and metabolic syndrome: a systematic review and meta-analysis.

BMC Pulm Med. 2015;15:105

Authors: Xu S, Wan Y, Xu M, Ming J, Xing Y, An F, Ji Q

Abstract
BACKGROUND: Obstructive sleep apnea (OSA) is characterized by repeated episodes of obstruction of the upper airway. Numerous studies have indicated a relationship between OSA and metabolic syndrome (MS), but the results remain debatable. We aimed to perform a systematic review and meta-analysis to evaluate the association between OSA and MS.
METHODS: We searched electronic databases (PubMed, EMBASE, and ISO Web of Knowledge) up to September 2014 with English-language restriction. Cross-sectional, case-control, and cohort studies in which the presence of OSA was assessed by objective measurements, the exposure of interest was OSA, and the outcome of interest was the presence (or incidence) of MS were included. The adjusted odds ratios (ORs) (or relative risk) and 95 % confidence intervals (CIs) were extracted and pooled. Sensitivity analyses were conducted, and heterogeneity and publication bias were assessed.
RESULTS: Overall, 15 cross-sectional (2456 patients with OSA and 1705 subjects without OSA), five case-control (1156 OSA patients and 404 controls), and no cohort studies were included. The pooled ORs of MS in individuals with OSA for cross-sectional and case-control studies were 2.87 (95 % CI: 2.41-3.42) and 2.56 (95 % CI: 1.98-3.31), respectively. There was clinically unimportant (I (2) = 20 %) and moderate (I (2) = 35 %) between-study heterogeneity of the analysis. The pooled crude ORs of MS in individuals with mild and moderate-to-severe OSA was 2.39 (95 % CI: 1.65-3.46) and 3.45 (95 % CI: 2.33-5.12), respectively, and there was substantial heterogeneity in the meta-analyses (I (2) = 53 % and I (2) = 63 %, respectively). However, no evidence of publication bias was detected.
CONCLUSIONS: OSA is shown to be associated with MS, although causality between these two factors has not been demonstrated yet. Future cohort and randomized controlled studies are needed.

PMID: 26391008 [PubMed - indexed for MEDLINE]



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Bacterial evolution in PCD and CF patients follows the same mutational steps.

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Bacterial evolution in PCD and CF patients follows the same mutational steps.

Sci Rep. 2016;6:28732

Authors: Sommer LM, Alanin MC, Marvig RL, Nielsen KG, Høiby N, von Buchwald C, Molin S, Johansen HK

Abstract
Infections with Pseudomonas aeruginosa increase morbidity in primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) patients. Both diseases are associated with a defect of the mucociliary clearance; in PCD caused by non-functional cilia, in CF by changed mucus. Whole genome sequencing of P. aeruginosa isolates from CF patients has shown that persistence of clonal lineages in the airways is facilitated by genetic adaptation. It is unknown whether this also applies to P. aeruginosa airway infections in PCD. We compared within-host evolution of P. aeruginosa in PCD and CF patients. P. aeruginosa isolates from 12 PCD patients were whole genome sequenced and phenotypically characterised. Ten out of 12 PCD patients were infected with persisting clone types. We identified convergent evolution in eight genes, which are also important for persistent infections in CF airways: genes related to antibiotic resistance, quorum sensing, motility, type III secretion and mucoidity. We document phenotypic and genotypic parallelism in the evolution of P. aeruginosa across infected patients with different genetic disorders. The parallel changes and convergent adaptation and evolution may be caused by similar selective forces such as the intensive antibiotic treatment and the inflammatory response, which drive the evolutionary processes.

PMID: 27349973 [PubMed - in process]



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Acute mental change and hemiplegia after autologous fat injection.

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Acute mental change and hemiplegia after autologous fat injection.

J Cosmet Laser Ther. 2016 Jun 28;:1-11

Authors: Kang JH, Park KH, Park JS

Abstract
Autologous fat injection is a common procedure used for skin augmentation. Although it is believed to be a safe and simple procedure, severe complications have been reported sometimes. The authors experienced the patient with acute large cerebral infarction including the territories of the anterior and middle cerebral arteries and optic nerve infarction developing after autologous fat transplantation. A 32-year-old woman was referred to the emergency room of our hospital due to sudden stupor. Thirty minutes earlier, she was undergoing cosmetic autologous fat injection into the glabella area by a plastic surgeon at private clinic. The cause was confirmed to be anterior and middle cerebral arteries infarction on brain imaging studies. When patient present abrupt mental change, hemiplegia, ocular pain, or blindness after autologous fat particle injection, physicians must consider cerebral infarction and combined retinal artery occlusion.

PMID: 27352047 [PubMed - as supplied by publisher]



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Routine preoperative colour Doppler duplex ultrasound scanning in anterior lateral thigh flaps.

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Routine preoperative colour Doppler duplex ultrasound scanning in anterior lateral thigh flaps.

Br J Oral Maxillofac Surg. 2016 Jun 24;

Authors: Lichte J, Teichmann J, Loberg C, Kloss-Brandstätter A, Bartella A, Steiner T, Modabber A, Hölzle F, Lethaus B

Abstract
The anterior lateral thigh flap (ALT) is often used to reconstruct the head and neck and depends on one or more skin perforators, which often present with variable anatomy. The aim of this study was to localise and evaluate the precise position of these perforators preoperatively with colour Doppler duplex ultrasound scanning (US). We detected 74 perforators in 30 patients. The mean duration of examination with colour Doppler was 29 (range 13-51) minutes. Adequate perforators and their anatomical course could be detected preoperatively extremely accurately (p<0.001). The mean difference between the preoperatively marked, and the real, positions was 6.3 (range 0-16) mm. There was a highly significant correlation between the accuracy of the prediction and the body mass index of the patient (0.75; p<0.001). Neither the age nor the sex of the patient correlated with the accuracy of the prediction. Colour Doppler duplex US used preoperatively to localise perforators in ALT flaps is reliable and could be adopted as standard procedure.

PMID: 27349963 [PubMed - as supplied by publisher]



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The Thyroid Hormone Inactivating Enzyme Type 3 Deiodinase is Present in Bactericidal Granules and the Cytoplasm of Human Neutrophils

Endocrinology, Early Release.


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Maternally administered cyclic-glycine-proline increases insulin-like growth factor-1 bioavailability and novelty recognition in developing offspring

Endocrinology, Early Release.


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Seminal plasma induces ovulation in llamas in the absence of a copulatory stimulus: role of nerve growth factor as an ovulation-inducing factor1

Endocrinology, Early Release.


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Seminal plasma induces ovulation in llamas in the absence of a copulatory stimulus: role of nerve growth factor as an ovulation-inducing factor1

Endocrinology, Early Release.


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Implications of Lateral Cerebellum in Proactive Control of Saccades

Although several lines of evidence establish the involvement of the medial and vestibular parts of the cerebellum in the adaptive control of eye movements, the role of the lateral hemisphere of the cerebellum in eye movements remains unclear. Ascending projections from the lateral cerebellum to the frontal and parietal association cortices via the thalamus are consistent with a role of these pathways in higher-order oculomotor control. In support of this, previous functional imaging studies and recent analyses in subjects with cerebellar lesions have indicated a role for the lateral cerebellum in volitional eye movements such as anti-saccades. To elucidate the underlying mechanisms, we recorded from single neurons in the dentate nucleus of the cerebellum in monkeys performing anti-saccade/pro-saccade tasks. We found that neurons in the posterior part of the dentate nucleus showed higher firing rates during the preparation of anti-saccades compared with pro-saccades. When the animals made erroneous saccades to the visual stimuli in the anti-saccade trials, the firing rate during the preparatory period decreased. Furthermore, local inactivation of the recording sites with muscimol moderately increased the proportion of error trials, while successful anti-saccades were more variable and often had shorter latency during inactivation. Thus, our results show that neuronal activity in the cerebellar dentate nucleus causally regulates anti-saccade performance. Neuronal signals from the lateral cerebellum to the frontal cortex might modulate the proactive control signals in the corticobasal ganglia circuitry that inhibit early reactive responses and possibly optimize the speed and accuracy of anti-saccades.

SIGNIFICANCE STATEMENT Although the lateral cerebellum is interconnected with the cortical eye fields via the thalamus and the pons, its role in eye movements remains unclear. We found that neurons in the caudal part of the lateral (dentate) nucleus of the cerebellum showed the increased firing rate during the preparation of anti-saccades. Inactivation of the recording sites modestly elevated the rate of erroneous saccades to the visual stimuli in the anti-saccade trials, while successful anti-saccades during inactivation tended to have a shorter latency. Our data indicate that neuronal signals in the lateral cerebellum may proactively regulate anti-saccade generation through the pathways to the frontal cortex, and may inhibit early reactive responses and regulate the accuracy of anti-saccades.



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Differential Excitation of Distally versus Proximally Targeting Cortical Interneurons by Unitary Thalamocortical Bursts

Thalamocortical neurons relay sensory and motor information to the neocortex using both single spikes and bursts; bursts prevail during low-vigilance states but also occur during awake behavior. Bursts are suggested to provide an alerting signal to the cortex and enhance stimulus detection, but the synaptic mechanisms underlying these effects are not clear, because the postsynaptic responses of different subtypes of cortical neurons to unitary thalamocortical bursts are mostly unknown. Using optogenetically guided recordings in mouse thalamocortical slices, we achieved the first reported paired intracellular recordings from nine monosynaptically connected thalamic and cortical neurons, including principal cells and two subtypes of inhibitory interneurons, and compared between cortical responses to single thalamocortical spikes and bursts. In 18 additional cortical neurons, we elicited unitary burst responses optogenetically. Short-term dynamics and temporal summation of burst-evoked EPSPs were cell-type dependent: in principal cells and somatostatin-containing (SOM), but not fast-spiking (FS), interneurons, peak response during a burst was on average more than twofold larger than the response to the first spike. Thus, firing a burst instead of a single spike would more than double the probability of firing in postsynaptic excitatory neurons and in SOM, but not FS, interneurons. Consistent with this prediction, FS interneurons held near firing threshold fired most often on the first burst component, whereas SOM interneurons fired only on the second or later components. By increasing excitation of principal cells together with SOM-mediated, distally directed inhibition, thalamocortical bursts could momentarily enhance the saliency of the ascending sensory stimulus over less urgent, top-down inputs.

SIGNIFICANCE STATEMENT Thalamocortical neurons relay sensory and motor information to the cerebral cortex using both single spikes and high-frequency bursts, but the function of bursts is not fully understood. Using brain slices from mouse somatosensory thalamus and cortex, we achieved the first dual recordings of directly connected thalamic and cortical neurons and compared between cortical responses to single thalamic spikes and to bursts. We report that bursts enhanced the responses of excitatory neurons and of inhibitory interneurons that preferentially target dendrites. A potential consequence is that bursts will enhance the response to the immediate sensory event over responses to less urgent, modulatory inputs.



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Presence of the hyperintense acute reperfusion marker on MRI after mechanical thrombectomy for large vessel occlusion is associated with worse early neurological recovery

Background

Mechanical thrombectomy has become the accepted treatment for large vessel occlusion in acute ischemic stroke. Unfortunately, a large cohort of patients do not achieve functional independence with treatment, even though the results are more robust than with medical management. The hyperintense acute reperfusion marker (HARM) on MRI is an indication of the breakdown of the blood–brain barrier and reperfusion injury.

Objective

To examine the hypothesis that the presence of HARM on MRI correlates with worse neurological recovery after reperfusion therapy.

Methods

We retrospectively reviewed 35 consecutive patients who between February 24, 2016 and April 23, 2016 underwent MRI to determine the presence of HARM after thrombectomy for anterior circulation large vessel occlusion. Demographic, radiographic imaging, and outcome data were collected. Univariate and binary logistic regression models were performed to assess predictors for improvement of the National Institutes of Health Stroke Scale (NIHSS) score by ≥8 points at 24 hours.

Results

The 35 patients studied had an average age of 64±14 years of age with a median NIHSS score of 15 (IQR 9–20). Eighteen patients (51%) were found to have a HARM-positive MRI. In univariate analysis, patients with HARM were older, had lower reperfusion rates and more postprocedural hemorrhages. In binary logistic regression modeling, the absence of HARM was independently associated with a ≥8-point NIHSS score improvement at 24 hours (OR=7.14, 95% CI 1.22 to 41.67).

Conclusions

This preliminary analysis shows that the presence of HARM may be linked to worse neurological recovery 24 hours after thrombectomy. Reperfusion injury may affect the number of patients achieving functional independence after treatment.



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Individualisierter oder Standardzugangsweg zum Abdomen

Zusammenfassung

Hintergrund

Jeder Bauchdeckenschnitt kann zu Früh- (z. B. Bauchdeckeninfektion) und Spätkomplikationen (z. B. Narbenhernie) führen. Die richtige Schnittführung ist oft schon entscheidend, um einerseits einen optimalen Zugang zum Operationsgebiet zu haben und andererseits Komplikationen möglichst gering zu halten.

Ziel der Arbeit

Die Auswertung der rezenten Literatur soll uns darüber Auskunft geben, ob bei bestimmten Entitäten ein bestimmter Zugangsweg zum Abdomen vorteilhaft gegenüber anderen Schnittführungen ist.

Material und Methoden

Es wurde eine Literaturrecherche mit dem Thema Abdominalzugänge in folgenden Datenbanken durchgeführt: Cochrane Database of Systematic Reviews (CDSR), Cochrane Library, Medline und PubMed. Systematische Reviews und Studien mit großen Fallzahlen wurden für die Auswertung herangezogen, wohingegen Studien mit kleinen Fallzahlen und „case reports" nicht berücksichtigt wurden.

Ergebnisse

Mittellinienlaparotomien sind für akute und elektive Abdominaleingriffe der Standardzugang, da die gute Abdominalübersicht und der rasche Zugangsweg zum Abdomen überzeugen. Bei großen Oberbauchoperationen kann die Querlaparotomie als gleichwertig angesehen werden mit dem Vorteil der guten Exploration von z. B. Leber oder Pankreas. 25 Jahre nach Einführung der Laparoskopie hat sich diese Technik als Standardzugangsweg bei der Cholezystektomie, bei der Fundoplikation und bei der Adipositaschirurgie etabliert. Beim akuten Appendix und bei vielen Kolonoperationen stellt sich das minimale Zugangstrauma als vorteilhaft in Bezug auf postoperative Schmerzen und den Spitalsaufenthalt dar, jedoch ist bei dieser Technik unter Umständen mit längeren Operationszeiten zu rechnen. Die SILS(„single incision laparoscopic surgery")-Technik punktet im kosmetischen Outcome, jedoch sind Narbenhernien, verlängerte Operationszeit und höhere Komplikationsraten für diese Technik limitierend. NOTES („natural orifice translumenal endoscopic surgery") und atypische Zugangswege kommen nur selten zur Anwendung.



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Grading von Lungenkarzinomen

Zusammenfassung

Im Vergleich mit anderen Tumorentitäten liegt für die Karzinome der Lunge aktuell noch kein einheitliches, allgemein akzeptiertes Gradingsystem mit klar definierten Kriterien und klinischer Signifikanz vor. In der 4. Auflage der WHO-Klassifikation von Tumoren der Lunge, der Pleura, des Thymus und des Herzens ist kein einheitliches Grading für pulmonale Adeno-, Plattenepithelkarzinome oder seltenere Tumorentitäten angegeben. Für die Adenokarzinome werden seit der 2011 publizierten IASLC/ATS/ERS-Klassifikation 5 unterschiedliche Subtypen mit signifikant unterschiedlicher Prognose vorgeschlagen. Daraus resultiert ein rein histologisches Grading, das üblicherweise an Resektaten eingesetzt wird. Bei den Plattenepithelkarzinomen wurde zwar die Anzahl der unterschiedlichen histologischen Subtypen in der neuen WHO-Klassifikation gegenüber früheren Versionen reduziert, es resultiert daraus jedoch kein einheitliches Gradingsystem. In aktuelleren Publikationen werden „nesting" und „budding" als wesentliche histologische Kriterien für ein Grading von Plattenepithelkarzinomen vorgeschlagen. Die neuroendokrinen Tumoren (NET) der Lunge werden in einer getrennten Arbeit dieses Themenhefts im Vergleich mit den NET anderer Organe abgehandelt.

Bestimmte seltenere Tumortypen sind per definitionem „high grade": kleinzellige, großzellige, pleomorphe Karzinome, Karzinosarkome und pulmonale Blastome. In der Zukunft ist zu erwarten, dass diese Entwicklungen weiter verstetigt und verfeinert werden, z. B. durch Einbeziehung weiterer Subtypen bei den Adenokarzinomen und ggf. auch zytologischer und/oder nukleärer Kriterien bei Adeno- und/oder Plattenepithelkarzinomen.



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The relationship between complement factor C3, APOE ε4, amyloid and tau in Alzheimer’s disease

Abstract

Inflammation is becoming increasingly recognized as an important contributor to Alzheimer's disease (AD) pathogenesis. As a part of the innate immune system, the complement cascade enhances the body's ability to destroy and remove pathogens and has recently been shown to influence Alzheimer's associated amyloid and tau pathology. However, little is known in humans about the effects of the complement system and genetic modifiers of AD risk like the ε4 allele of apolioprotein E (APOE ε4) on AD pathobiology. We evaluated cerebrospinal fluid (CSF) protein levels from 267 individuals clinically diagnosed as cognitively normal, mild cognitive impairment, and AD. Using linear models, we assessed the relationship between APOE ε4 genotype, CSF Complement 3 (C3), CSF amyloid-β (amyloid) and CSF hyperphosphorylated tau (ptau). We found a significant interaction between APOE ε4 and CSF C3 on both CSF amyloid and CSF ptau. We also found that CSF C3 is only associated with CSF ptau after accounting for CSF amyloid. Our results support a conceptual model of the AD pathogenic cascade where a synergistic relationship between the complement cascade (C3) and APOE ε4 results in elevated Alzheimer's neurodegeneration and in turn, amyloid further regulates the effect of the complement cascade on downstream tau pathology.



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Extension of Helix 12 in Munc18-1 Induces Vesicle Priming

Munc18-1 is essential for vesicle fusion and participates in the docking of large dense-core vesicles to the plasma membrane. Recent structural data suggest that conformational changes in the 12th helix of the Munc18-1 domain 3a within the Munc18-1:syntaxin complex result in an additional interaction with synaptobrevin-2/VAMP2 (vesicle-associated membrane protein 2), leading to SNARE complex formation. To test this hypothesis in living cells, we examined secretion from Munc18-1-null mouse adrenal chromaffin cells expressing Munc18-1 mutants designed to either perturb the extension of helix 12 (324–339), block its interaction with synaptobrevin-2 (L348R), or extend the helix to promote coil–coil interactions with other proteins (P335A). The mutants rescued vesicle docking and syntaxin-1 targeting to the plasma membrane, with the exception of P335A that only supported partial syntaxin-1 targeting. Disruptive mutations (L348R or 324–339) lowered the secretory amplitude by decreasing vesicle priming, whereas P335A markedly increased priming and secretory amplitude. The mutants displayed unchanged kinetics and Ca2+ dependence of fusion, indicating that the mutations specifically affect the vesicle priming step. Mutation of a nearby tyrosine (Y337A), which interacts with closed syntaxin-1, mildly increased secretory amplitude. This correlated with results from an in vitro fusion assay probing the functions of Munc18-1, indicating an easier transition to the extended state in the mutant. Our findings support the notion that a conformational transition within the Munc18-1 domain 3a helix 12 leads to opening of a closed Munc18-1:syntaxin complex, followed by productive SNARE complex assembly and vesicle priming.

SIGNIFICANCE STATEMENT The essential postdocking role of Munc18-1 in vesicular exocytosis has remained elusive, but recent data led to the hypothesis that the extension of helix 12 in Munc18 within domain 3a leads to synaptobrevin-2/VAMP2 interaction and SNARE complex formation. Using both lack-of-function and gain-of-function mutants, we here report that the conformation of helix 12 predicts vesicle priming and secretory amplitude in living chromaffin cells. The effects of mutants on secretion could not be explained by differences in syntaxin-1 chaperoning/localization or vesicle docking, and the fusion kinetics and calcium dependence were unchanged, indicating that the effect of helix 12 extension is specific for the vesicle-priming step. We conclude that a conformational change within helix 12 is responsible for the essential postdocking role of Munc18-1 in neurosecretion.



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Dynamic Modulation of Myelination in Response to Visual Stimuli Alters Optic Nerve Conduction Velocity

Myelin controls the time required for an action potential to travel from the neuronal soma to the axon terminal, defining the temporal manner in which information is processed within the CNS. The presence of myelin, the internodal length, and the thickness of the myelin sheath are powerful structural factors that control the velocity and fidelity of action potential transmission. Emerging evidence indicates that myelination is sensitive to environmental experience and neuronal activity. Activity-dependent modulation of myelination can dynamically alter action potential conduction properties but direct functional in vivo evidence and characterization of the underlying myelin changes is lacking. We demonstrate that in mice long-term monocular deprivation increases oligodendrogenesis in the retinogeniculate pathway but shortens myelin internode lengths without affecting other structural properties of myelinated fibers. We also demonstrate that genetically attenuating synaptic glutamate neurotransmission from retinal ganglion cells phenocopies the changes observed after monocular deprivation, suggesting that glutamate may constitute a signal for myelin length regulation. Importantly, we demonstrate that visual deprivation and shortened internodes are associated with a significant reduction in nerve conduction velocity in the optic nerve. Our results reveal the importance of sensory input in the building of myelinated fibers and suggest that this activity-dependent alteration of myelination is important for modifying the conductive properties of brain circuits in response to environmental experience.

SIGNIFICANCE STATEMENT Oligodendrocyte precursor cells differentiate into mature oligodendrocytes and are capable of ensheathing axons with myelin without molecular cues from neurons. However, this default myelination process can be modulated by changes in neuronal activity. Here, we show, for the first time, that experience-dependent activity modifies the length of myelin internodes along axons altering action potential conduction velocity. Such a mechanism would allow for variations in conduction velocities that provide a degree of plasticity in accordance to environmental needs. It will be important in future work to investigate how these changes in myelination and conduction velocity contribute to signal integration in postsynaptic neurons and circuit function.



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Effect of Rhodopsin Phosphorylation on Dark Adaptation in Mouse Rods

Rhodopsin is a prototypical G-protein-coupled receptor (GPCR) that is activated when its 11-cis-retinal moiety is photoisomerized to all-trans retinal. This step initiates a cascade of reactions by which rods signal changes in light intensity. Like other GPCRs, rhodopsin is deactivated through receptor phosphorylation and arrestin binding. Full recovery of receptor sensitivity is then achieved when rhodopsin is regenerated through a series of steps that return the receptor to its ground state. Here, we show that dephosphorylation of the opsin moiety of rhodopsin is an extremely slow but requisite step in the restoration of the visual pigment to its ground state. We make use of a novel observation: isolated mouse retinae kept in standard media for routine physiologic recordings display blunted dephosphorylation of rhodopsin. Isoelectric focusing followed by Western blot analysis of bleached isolated retinae showed little dephosphorylation of rhodopsin for up to 4 h in darkness, even under conditions when rhodopsin was completely regenerated. Microspectrophotometeric determinations of rhodopsin spectra show that regenerated phospho-rhodopsin has the same molecular photosensitivity as unphosphorylated rhodopsin and that flash responses measured by trans-retinal electroretinogram or single-cell suction electrode recording displayed dark-adapted kinetics. Single quantal responses displayed normal dark-adapted kinetics, but rods were only half as sensitive as those containing exclusively unphosphorylated rhodopsin. We propose a model in which light-exposed retinae contain a mixed population of phosphorylated and unphosphorylated rhodopsin. Moreover, complete dark adaptation can only occur when all rhodopsin has been dephosphorylated, a process that requires >3 h in complete darkness.

SIGNIFICANCE STATEMENT G-protein-coupled receptors (GPCRs) constitute the largest superfamily of proteins that compose ~4% of the mammalian genome whose members share a common membrane topology. Signaling by GPCRs regulate a wide variety of physiological processes, including taste, smell, hearing, vision, and cardiovascular, endocrine, and reproductive homeostasis. An important feature of GPCR signaling is its timely termination. This normally occurs when, after their activation, GPCRs are rapidly phosphorylated by specific receptor kinases and subsequently bound by cognate arrestins. Recovery of receptor sensitivity to the ground state then requires dephosphorylation of the receptor and unbinding of arrestin, processes that are poorly understood. Here we investigate in mouse rod photoreceptors the relationship between rhodopsin dephosphorylation and recovery of visual sensitivity.



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The Thyroid Hormone Inactivating Enzyme Type 3 Deiodinase is Present in Bactericidal Granules and the Cytoplasm of Human Neutrophils

Endocrinology, Early Release.


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Maternally administered cyclic-glycine-proline increases insulin-like growth factor-1 bioavailability and novelty recognition in developing offspring

Endocrinology, Early Release.


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Seminal plasma induces ovulation in llamas in the absence of a copulatory stimulus: role of nerve growth factor as an ovulation-inducing factor1

Endocrinology, Early Release.


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Seminal plasma induces ovulation in llamas in the absence of a copulatory stimulus: role of nerve growth factor as an ovulation-inducing factor1

Endocrinology, Early Release.


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Implications of Lateral Cerebellum in Proactive Control of Saccades

Although several lines of evidence establish the involvement of the medial and vestibular parts of the cerebellum in the adaptive control of eye movements, the role of the lateral hemisphere of the cerebellum in eye movements remains unclear. Ascending projections from the lateral cerebellum to the frontal and parietal association cortices via the thalamus are consistent with a role of these pathways in higher-order oculomotor control. In support of this, previous functional imaging studies and recent analyses in subjects with cerebellar lesions have indicated a role for the lateral cerebellum in volitional eye movements such as anti-saccades. To elucidate the underlying mechanisms, we recorded from single neurons in the dentate nucleus of the cerebellum in monkeys performing anti-saccade/pro-saccade tasks. We found that neurons in the posterior part of the dentate nucleus showed higher firing rates during the preparation of anti-saccades compared with pro-saccades. When the animals made erroneous saccades to the visual stimuli in the anti-saccade trials, the firing rate during the preparatory period decreased. Furthermore, local inactivation of the recording sites with muscimol moderately increased the proportion of error trials, while successful anti-saccades were more variable and often had shorter latency during inactivation. Thus, our results show that neuronal activity in the cerebellar dentate nucleus causally regulates anti-saccade performance. Neuronal signals from the lateral cerebellum to the frontal cortex might modulate the proactive control signals in the corticobasal ganglia circuitry that inhibit early reactive responses and possibly optimize the speed and accuracy of anti-saccades.

SIGNIFICANCE STATEMENT Although the lateral cerebellum is interconnected with the cortical eye fields via the thalamus and the pons, its role in eye movements remains unclear. We found that neurons in the caudal part of the lateral (dentate) nucleus of the cerebellum showed the increased firing rate during the preparation of anti-saccades. Inactivation of the recording sites modestly elevated the rate of erroneous saccades to the visual stimuli in the anti-saccade trials, while successful anti-saccades during inactivation tended to have a shorter latency. Our data indicate that neuronal signals in the lateral cerebellum may proactively regulate anti-saccade generation through the pathways to the frontal cortex, and may inhibit early reactive responses and regulate the accuracy of anti-saccades.



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Differential Excitation of Distally versus Proximally Targeting Cortical Interneurons by Unitary Thalamocortical Bursts

Thalamocortical neurons relay sensory and motor information to the neocortex using both single spikes and bursts; bursts prevail during low-vigilance states but also occur during awake behavior. Bursts are suggested to provide an alerting signal to the cortex and enhance stimulus detection, but the synaptic mechanisms underlying these effects are not clear, because the postsynaptic responses of different subtypes of cortical neurons to unitary thalamocortical bursts are mostly unknown. Using optogenetically guided recordings in mouse thalamocortical slices, we achieved the first reported paired intracellular recordings from nine monosynaptically connected thalamic and cortical neurons, including principal cells and two subtypes of inhibitory interneurons, and compared between cortical responses to single thalamocortical spikes and bursts. In 18 additional cortical neurons, we elicited unitary burst responses optogenetically. Short-term dynamics and temporal summation of burst-evoked EPSPs were cell-type dependent: in principal cells and somatostatin-containing (SOM), but not fast-spiking (FS), interneurons, peak response during a burst was on average more than twofold larger than the response to the first spike. Thus, firing a burst instead of a single spike would more than double the probability of firing in postsynaptic excitatory neurons and in SOM, but not FS, interneurons. Consistent with this prediction, FS interneurons held near firing threshold fired most often on the first burst component, whereas SOM interneurons fired only on the second or later components. By increasing excitation of principal cells together with SOM-mediated, distally directed inhibition, thalamocortical bursts could momentarily enhance the saliency of the ascending sensory stimulus over less urgent, top-down inputs.

SIGNIFICANCE STATEMENT Thalamocortical neurons relay sensory and motor information to the cerebral cortex using both single spikes and high-frequency bursts, but the function of bursts is not fully understood. Using brain slices from mouse somatosensory thalamus and cortex, we achieved the first dual recordings of directly connected thalamic and cortical neurons and compared between cortical responses to single thalamic spikes and to bursts. We report that bursts enhanced the responses of excitatory neurons and of inhibitory interneurons that preferentially target dendrites. A potential consequence is that bursts will enhance the response to the immediate sensory event over responses to less urgent, modulatory inputs.



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Presence of the hyperintense acute reperfusion marker on MRI after mechanical thrombectomy for large vessel occlusion is associated with worse early neurological recovery

Background

Mechanical thrombectomy has become the accepted treatment for large vessel occlusion in acute ischemic stroke. Unfortunately, a large cohort of patients do not achieve functional independence with treatment, even though the results are more robust than with medical management. The hyperintense acute reperfusion marker (HARM) on MRI is an indication of the breakdown of the blood–brain barrier and reperfusion injury.

Objective

To examine the hypothesis that the presence of HARM on MRI correlates with worse neurological recovery after reperfusion therapy.

Methods

We retrospectively reviewed 35 consecutive patients who between February 24, 2016 and April 23, 2016 underwent MRI to determine the presence of HARM after thrombectomy for anterior circulation large vessel occlusion. Demographic, radiographic imaging, and outcome data were collected. Univariate and binary logistic regression models were performed to assess predictors for improvement of the National Institutes of Health Stroke Scale (NIHSS) score by ≥8 points at 24 hours.

Results

The 35 patients studied had an average age of 64±14 years of age with a median NIHSS score of 15 (IQR 9–20). Eighteen patients (51%) were found to have a HARM-positive MRI. In univariate analysis, patients with HARM were older, had lower reperfusion rates and more postprocedural hemorrhages. In binary logistic regression modeling, the absence of HARM was independently associated with a ≥8-point NIHSS score improvement at 24 hours (OR=7.14, 95% CI 1.22 to 41.67).

Conclusions

This preliminary analysis shows that the presence of HARM may be linked to worse neurological recovery 24 hours after thrombectomy. Reperfusion injury may affect the number of patients achieving functional independence after treatment.



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Individualisierter oder Standardzugangsweg zum Abdomen

Zusammenfassung

Hintergrund

Jeder Bauchdeckenschnitt kann zu Früh- (z. B. Bauchdeckeninfektion) und Spätkomplikationen (z. B. Narbenhernie) führen. Die richtige Schnittführung ist oft schon entscheidend, um einerseits einen optimalen Zugang zum Operationsgebiet zu haben und andererseits Komplikationen möglichst gering zu halten.

Ziel der Arbeit

Die Auswertung der rezenten Literatur soll uns darüber Auskunft geben, ob bei bestimmten Entitäten ein bestimmter Zugangsweg zum Abdomen vorteilhaft gegenüber anderen Schnittführungen ist.

Material und Methoden

Es wurde eine Literaturrecherche mit dem Thema Abdominalzugänge in folgenden Datenbanken durchgeführt: Cochrane Database of Systematic Reviews (CDSR), Cochrane Library, Medline und PubMed. Systematische Reviews und Studien mit großen Fallzahlen wurden für die Auswertung herangezogen, wohingegen Studien mit kleinen Fallzahlen und „case reports" nicht berücksichtigt wurden.

Ergebnisse

Mittellinienlaparotomien sind für akute und elektive Abdominaleingriffe der Standardzugang, da die gute Abdominalübersicht und der rasche Zugangsweg zum Abdomen überzeugen. Bei großen Oberbauchoperationen kann die Querlaparotomie als gleichwertig angesehen werden mit dem Vorteil der guten Exploration von z. B. Leber oder Pankreas. 25 Jahre nach Einführung der Laparoskopie hat sich diese Technik als Standardzugangsweg bei der Cholezystektomie, bei der Fundoplikation und bei der Adipositaschirurgie etabliert. Beim akuten Appendix und bei vielen Kolonoperationen stellt sich das minimale Zugangstrauma als vorteilhaft in Bezug auf postoperative Schmerzen und den Spitalsaufenthalt dar, jedoch ist bei dieser Technik unter Umständen mit längeren Operationszeiten zu rechnen. Die SILS(„single incision laparoscopic surgery")-Technik punktet im kosmetischen Outcome, jedoch sind Narbenhernien, verlängerte Operationszeit und höhere Komplikationsraten für diese Technik limitierend. NOTES („natural orifice translumenal endoscopic surgery") und atypische Zugangswege kommen nur selten zur Anwendung.



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Grading von Lungenkarzinomen

Zusammenfassung

Im Vergleich mit anderen Tumorentitäten liegt für die Karzinome der Lunge aktuell noch kein einheitliches, allgemein akzeptiertes Gradingsystem mit klar definierten Kriterien und klinischer Signifikanz vor. In der 4. Auflage der WHO-Klassifikation von Tumoren der Lunge, der Pleura, des Thymus und des Herzens ist kein einheitliches Grading für pulmonale Adeno-, Plattenepithelkarzinome oder seltenere Tumorentitäten angegeben. Für die Adenokarzinome werden seit der 2011 publizierten IASLC/ATS/ERS-Klassifikation 5 unterschiedliche Subtypen mit signifikant unterschiedlicher Prognose vorgeschlagen. Daraus resultiert ein rein histologisches Grading, das üblicherweise an Resektaten eingesetzt wird. Bei den Plattenepithelkarzinomen wurde zwar die Anzahl der unterschiedlichen histologischen Subtypen in der neuen WHO-Klassifikation gegenüber früheren Versionen reduziert, es resultiert daraus jedoch kein einheitliches Gradingsystem. In aktuelleren Publikationen werden „nesting" und „budding" als wesentliche histologische Kriterien für ein Grading von Plattenepithelkarzinomen vorgeschlagen. Die neuroendokrinen Tumoren (NET) der Lunge werden in einer getrennten Arbeit dieses Themenhefts im Vergleich mit den NET anderer Organe abgehandelt.

Bestimmte seltenere Tumortypen sind per definitionem „high grade": kleinzellige, großzellige, pleomorphe Karzinome, Karzinosarkome und pulmonale Blastome. In der Zukunft ist zu erwarten, dass diese Entwicklungen weiter verstetigt und verfeinert werden, z. B. durch Einbeziehung weiterer Subtypen bei den Adenokarzinomen und ggf. auch zytologischer und/oder nukleärer Kriterien bei Adeno- und/oder Plattenepithelkarzinomen.



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The relationship between complement factor C3, APOE ε4, amyloid and tau in Alzheimer’s disease

Abstract

Inflammation is becoming increasingly recognized as an important contributor to Alzheimer's disease (AD) pathogenesis. As a part of the innate immune system, the complement cascade enhances the body's ability to destroy and remove pathogens and has recently been shown to influence Alzheimer's associated amyloid and tau pathology. However, little is known in humans about the effects of the complement system and genetic modifiers of AD risk like the ε4 allele of apolioprotein E (APOE ε4) on AD pathobiology. We evaluated cerebrospinal fluid (CSF) protein levels from 267 individuals clinically diagnosed as cognitively normal, mild cognitive impairment, and AD. Using linear models, we assessed the relationship between APOE ε4 genotype, CSF Complement 3 (C3), CSF amyloid-β (amyloid) and CSF hyperphosphorylated tau (ptau). We found a significant interaction between APOE ε4 and CSF C3 on both CSF amyloid and CSF ptau. We also found that CSF C3 is only associated with CSF ptau after accounting for CSF amyloid. Our results support a conceptual model of the AD pathogenic cascade where a synergistic relationship between the complement cascade (C3) and APOE ε4 results in elevated Alzheimer's neurodegeneration and in turn, amyloid further regulates the effect of the complement cascade on downstream tau pathology.



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Tight Coupling of Astrocyte pH Dynamics to Epileptiform Activity Revealed by Genetically Encoded pH Sensors

Astrocytes can both sense and shape the evolution of neuronal network activity and are known to possess unique ion regulatory mechanisms. Here we explore the relationship between astrocytic intracellular pH dynamics and the synchronous network activity that occurs during seizure-like activity. By combining confocal and two-photon imaging of genetically encoded pH reporters with simultaneous electrophysiological recordings, we perform pH measurements in defined cell populations and relate these to ongoing network activity. This approach reveals marked differences in the intracellular pH dynamics between hippocampal astrocytes and neighboring pyramidal neurons in rodent in vitro models of epilepsy. With three different genetically encoded pH reporters, astrocytes are observed to alkalinize during epileptiform activity, whereas neurons are observed to acidify. In addition to the direction of pH change, the kinetics of epileptiform-associated intracellular pH transients are found to differ between the two cell types, with astrocytes displaying significantly more rapid changes in pH. The astrocytic alkalinization is shown to be highly correlated with astrocytic membrane potential changes during seizure-like events and mediated by an electrogenic Na+/HCO3 cotransporter. Finally, comparisons across different cell-pair combinations reveal that astrocytic pH dynamics are more closely related to network activity than are neuronal pH dynamics. This work demonstrates that astrocytes exhibit distinct pH dynamics during periods of epileptiform activity, which has relevance to multiple processes including neurometabolic coupling and the control of network excitability.

SIGNIFICANCE STATEMENT Dynamic changes in intracellular ion concentrations are central to the initiation and progression of epileptic seizures. However, it is not known how changes in intracellular H+ concentration (ie, pH) differ between different cell types during seizures. Using recently developed pH-sensitive proteins, we demonstrate that astrocytes undergo rapid alkalinization during periods of seizure-like activity, which is in stark contrast to the acidification that occurs in neighboring neurons. Rapid astrocytic pH changes are highly temporally correlated with seizure activity, are mediated by an electrogenic Na+/HCO3– cotransporter, and are more tightly coupled to network activity than are neuronal pH changes. As pH has profound effects on signaling in the nervous system, this work has implications for our understanding of seizure dynamics.



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Colonisation with methicillin-resistant Staphylococcus aureus and associated factors among nurses with occupational skin diseases

Objectives

To evaluate the prevalence of colonisation with methicillin-resistant Staphylococcus aureus (MRSA), associated factors and the effectiveness of decolonisation procedures among nurses with occupational skin diseases (OSD).

Methods

In a retrospective cohort study, the medical records of 319 nurses from Germany who were screened consecutively for MRSA when participating in a tertiary individual prevention programme (TIP) for severe OSD between July 2009 and December 2014 were evaluated.

Results

90.3% of nurses with severe OSD suffered from hand eczema. 43 were colonised with MRSA on admission (13.5%), mainly in the nose (n=35, 81.4%). However, the hands were affected in more than half of the MRSA carriers (n=24, 55.8%). Risk factors for MRSA colonisation were atopic skin diathesis (OR 2.01, 95% CI 1.03 to 3.92, p=0.049) and presence of atopic dermatitis on other body parts than the hands (OR 4.33, 95% CI 2.23 to 8.43, p<0.001). Hand eczema was significantly more severe in MRSA carriers than in non-carriers (OR 1.23, 95% CI 1.10 to 1.37, p<0.001) and showed a higher prevalence of vesicles, erosions or fissures. MRSA eradication was successful in 67.4% after the first attempt.

Conclusions

Nurses with OSD have a twofold to threefold higher prevalence of MRSA colonisation than what has been reported for point-prevalence screenings among healthcare workers in Germany. Atopic skin diathesis, atopic dermatitis and severe hand eczema are the main risk factors. Thus, prevention and treatment of OSD could be important elements in reduction of colonisation with MRSA among nurses and transmission to others.



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Occupational exposure of cashiers to Bisphenol A via thermal paper: urinary biomonitoring study

Abstract

Purpose

As an essential component of polycarbonate plastics and epoxy resins, Bisphenol A (BPA) is found in numerous industrial and consumer products. BPA may cause adverse health effects because of its endocrine activity. General population exposure to this compound mainly through diet is well documented. Thermal paper was also identified as a source of BPA through dermal intake. In this study, we investigated whether frequent contact with thermal paper is associated with an increase in urinary BPA excretion.

Methods

We evaluated the exposure to BPA in cashiers and in non-occupationally exposed workers from several workplaces. Urinary BPA was quantified in free (unconjugated) and total (unconjugated plus conjugated) forms in 24-h and spot urine samples using LC–MS/MS. BPA concentration in thermal paper was also measured from each workplace. In addition, participants provided information on job, food and drink, tobacco consumption and hands wash during the sampling period through a questionnaire.

Results

Urine samples were collected from 90 cashiers and 44 controls. Free and total BPA were detected in all samples. The median urinary total BPA concentration was 3.54 µg/L (2.89 µg/g creatinine) for controls and 8.92 µg/L (6.76 µg/g creatinine) for cashiers. For the free BPA, the median urinary concentration was 0.20 µg/L (0.21 µg/g creatinine) for controls and 0.28 µg/L (0.22 µg/g creatinine) for cashiers. Any correlation was found between the urinary concentration levels and the number of thermal receipts handled. Hand washes frequency, age, job length of service and tobacco consumption had also no effect on the BPA excretions.

Conclusion

A significant increase in urinary total BPA concentration was observed for cashiers handling daily thermal paper receipts. However, no significant increase was observed in urinary free BPA concentration. These findings are particularly interesting for risk assessment since all available data on occupational exposure to BPA through thermal paper were obtained from models or from simulated experiments.



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Reducing the underreporting of lung cancer attributable to occupation: outcomes from a hospital-based systematic search in Northern Italy

Abstract

Purpose

Occupational exposure to lung carcinogens is and was common in workplaces. 5–25 % of lung cancers (LCs) could be causally attributable to occupation; however, LC underreporting and undercompensation are widespread, with remarkable tolls paid by individuals and society. This work aims to: describe an ongoing hospital-based systematic search (SS) of occupational LC; improve aetiological diagnosis; increase number and quality of LC notifications.

Methods

Through a short form, physicians at a public hospital referred incident LC to the Occupational Health Unit (OHU). Only patients selected through the form were interviewed; a personal, occupational and clinical history was collected; reports were sent to the ward and Local Health Authority, with aetiological diagnosis criteria and probability of causation.

Results

From 1998 to 2013, 3274 cases of LC were notified to the OHU; prior to the system, just couple of dozens were assessed. A total of 1522 patients were fully interviewed; in 395 cases, causation was attributed to occupation (26 % of interviewed patients); all were notified to authorities, as compared to the handful reported before the system was adopted. Main aetiological agents were silica, asbestos, polycyclic aromatic hydrocarbons, truck driving, painting, multiple exposures. Compensation rate was remarkable (39 %).

Conclusions

Through SS, many occupational LCs were found that otherwise would have been lost. Aetiological diagnosis proved to be rich of scientific advantages and practical implications, with attention to equity and social aspects. SS was easy, accountable and fostered multidisciplinary collaboration among medical specialties, significantly reducing underreporting and undercompensation of occupational LC.



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Factors associated with alcohol abuse and dependence among public transport workers in the metropolitan region of Belo Horizonte

Abstract

Purpose

Alcohol use may be associated with occupational factors. The objective of this study was to describe the prevalence and identify factors independently associated with alcohol abuse and dependence among urban public workers.

Methods

In this cross-sectional study, a proportional sample of 1607 bus drivers and conductors in three municipalities within the metropolitan region of Belo Horizonte was analyzed (total population: 17,740). Face-to-face interviews were conducted using a digital questionnaire that investigated working conditions and health. Affirmative responses to at least two questions in the CAGE questionnaire were considered to represent situations of abuse and dependence. The magnitude of the associations was estimated by means of logistic regression in univariable and multivariable models.

Results

The prevalence of alcohol abuse and dependence was 13.5 %. Positive associations with the following were identified: lower schooling level (incomplete high school: OR 1.77; 95 % CI 1.14–2.74; and elementary education: OR 1.57; 95 % CI 1.10–2.26); current smoking (OR 2.12; 95 % CI 1.47–3.07); non-participation in social activities (OR 1.74; 95 % CI 1.21–2.48); medical diagnosis of three of more diseases (OR 1.57; 95 % CI 1.01–2.42); aggression at work (OR 1.39; 95 % CI 1.01–1.93); and work-related distress (OR 1.85; 95 % CI 1.27–2.71). Workers who did not have children presented a lower chance of alcohol abuse and dependence than did those with children (OR 0.67; 95 % CI 0.45–0.99).

Conclusions

Results of this study point that the urban public transport workers, users of public transport and also pedestrians could be on increased risk of accidents. So considering the importance of this service for all society and the risk involved in this activity, prospective studies are needed to clarify the relationships observed.



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Modifying effect of cigarette smoking on the association of organizational justice with serious psychological distress in Japanese employees: a cross-sectional study

Abstract

Purpose

We examined the modifying effect of cigarette smoking (i.e., smokers vs. non-smokers) on the association of organizational justice (i.e., procedural justice and interactional justice) with serious psychological distress (SPD) in Japanese employees.

Methods

Overall, 2838 participants from two factories of a manufacturing company in Japan completed a self-administered questionnaire comprising the scales on organizational justice (Organizational Justice Questionnaire), smoking status, psychological distress (K6 scale), demographic and occupational characteristics (i.e., gender, age, education, family size, history of depression, chronic physical conditions, occupation, and work form), and other health-related behaviors (i.e., drinking habit and physical activity). Multiple logistic regression analyses were conducted. In a series of analyses, interaction term of procedural justice or interactional justice with smoking status was included in the model.

Results

After adjusting for demographic and occupational characteristics as well as other health-related behaviors, low procedural justice and low interactional justice were significantly associated with SPD (defined as K6 ≥ 13). Furthermore, marginally significant interaction effect of procedural justice with smoking status was observed. Specifically, the association of low procedural justice with SPD was greater among smokers [prevalence odds ratio 7.13 (95 % confidence interval 3.25–15.7) for low vs. high procedural justice subgroup] than among non-smokers [prevalence odds ratio 2.34 (95 % confidence interval 1.52–3.60) for low vs. high procedural justice subgroup]. On the other hand, interaction effect of interactional justice with smoking status was not significant.

Conclusions

Cigarette smoking seems to have a harmful effect on the association of the lack of procedural justice with SPD in Japanese employees.



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Biological effects of inhaled nitrogen dioxide in healthy human subjects

Abstract

Purpose

Several epidemiological studies indicate that inhaled nitrogen dioxide (NO2) at low concentrations have been statistically associated with adverse health effects. However, these results are not reflected by exposure studies in humans. The aim of the study was to assess the acute functional and cellular responses to different NO2 concentrations in healthy human subjects with various techniques.

Methods

Twenty-five subjects were exposed for 3 h to NO2 concentrations 0, 0.1, 0.5, and 1.5 ppm in a randomized crossover study design during 4 consecutive weeks. In each subject, lung function, diffusion capacity and exhaled nitric oxide were measured and inflammation markers were assessed in blood, nasal secretions, induced sputum and exhaled breath condensate.

Results

From all lung function indices under consideration, only intrathoracic gas volume was borderline significantly increased after 0.5 ppm (p = 0.048) compared to 0.1 ppm NO2. Regarding the cellular effect parameters, the macrophage concentration in induced sputum decreased with increasing NO2 concentration, although these changes were only borderline significant (p = 0.05).

Conclusion

These results do not suggest a considerable acute adverse response in human subjects after 3 h of exposure to NO2 in the NO2 concentration range investigated in this study.



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Current Strategy for the Treatment of Ovarian Germ Cell Tumors: Role of Extensive Surgery

Opinion Statement

The necessity and extent of comprehensive surgical staging (CSS) and lymphadenectomy in the treatment of malignant ovarian germ cell tumors (MOGCTs) is still controversial. However, it is uniformly agreed that CSS with lymphadenectomy is crucial to follow up patients without adjuvant chemotherapy in stage I MOGCTs. Considering the chemotherapy-sensitive nature of MOGCTs, fertility-sparing cytoreductive surgery (FSCS) seems a reasonable approach in initial treatment for patients with advanced stage. When encountered with bilateral MOGCTs, debulking is surely granted if there is no desire for fertility. Both ovaries completely replaced by neoplastic tissue composed the most challenging situation especially when patients require childbearing potential. In dysgerminoma histology, which usually has good prognosis, residual disease could be left to spare fertility. USO of the largest and more heterogeneous ovarian mass and a biopsy of the contralateral lesion may be considered if the patients are compliant to regular follow-up. NACT followed by interval FSCS may be a reasonable option in patients with extensive disease, when initial debulking is not an option or where the poor general condition or clinical findings suggest an increased risk of surgical morbidity or preclude fertility-sparing surgery. This is currently not the standard of care but deserves future study. In some rare situation, when any remaining ovarian tissue means high risk, BSO may be performed with the uterus preserved for possible assisted reproduction with donor egg. Treatment failure occurs in a small group of MOGCTs after primary treatment. A good number of recurrences can be salvaged with selected salvage surgery, especially when optimal secondary cytoreduction can be achieved. Immature teratoma is a subtype of MOGCTs where secondary cytoreduction may have a strong role to play.



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10 obsolete EMT skills

Nothing makes me feel older than when I drop a casual reference to an EMT skill in a continuing education class and several bewildered young EMTs raise their hands hesitantly and ask, "Kelly, what are MAST pants?"

It got me to thinking how different the EMS profession is now from what it was when my career began. Medicine is a continually evolving process, and advances in technology come so rapidly that the current generation of EMS providers is working with a markedly different knowledge base and set of skills than the last one.

So gather around the campfire children and let Uncle Kelly tell you how we did it in the old days. Each of these 10 skills is something we used to commonly do, but are rarely, if ever, used any longer.

10. Pneumatic Anti-Shock Garments
I only spell it out because if I said MAST or PASG, I'd still have to explain it to you young whippersnappers. See, back in the day we used to put these inflatable Velcro pants on shock patients, and when inflated, it raised their blood pressure. It did raise blood pressure very well — to the point that the patient bled pink from all the IV fluids we gave, but those magic pants sucked at saving lives.

Not only did we have to know the different methods of applying them, like the diaper method and the pajama method, we also had to memorize the criteria for removal. Dinosaurs, say them with me now: "Bilateral large bore IV access, two units of typed and matched blood, surgical team on standby, deflate the abdominal section for 10 seconds, recheck the blood pressure …"

9. Manual defibrillation paddles
You kids these days with your hippity-hop music and your iThings and your hands-free multifunction electrodes.… Why, in my day, when we wanted to defibrillate someone, we had these things called paddles. And you had to apply conductive gel to them and smear it around; then you had to press them on the chest with at least 25 pounds of paddle pressure

And you had your energy select dial and defib button right there on the paddles. And you did this thing called a quick look, so that you could immediately shock the patient, like, three times in a row, before you even attached the monitor leads.

And by God, we were grateful.

8. Esophageal Obturator Airways
Imagine if a Combitube and a BVM had a baby, and the airway baby inherited the worst features of each. The EOA was a supraglottic airway that was bulky, often caused trauma on insertion, did a poor job of isolating the trachea and protecting against aspiration and still required that you maintain a mask seal.

And to think that nobody uses these beauties anymore! Crazy, right?

7. Oral screws
Picture — because I am afraid of what you might stumble across if you Google "oral screws" — if you will a little plastic doohickey shaped like a miniature ice cream cone with threads on the outer surface and a T-handle on the large end. And what you did was insert the small end of this doohickey between someone's teeth when their jaws were clenched, and screwed it in until it forced their jaws apart.

We used to do this whenever someone had a seizure, in the mistaken belief that if we didn't get their mouth open, they'd swallow their tongue.

But the real reason was that it gave paramedics with a juvenile sense of humor the opportunity to hold out their hands and bark, "Gimme an oral screw!"

I'm telling you, that one never got old.

6. Taping stuff down
When I was a paramedic student, my instructor took great pains to show us how to tear thin little strips of adhesive tape to secure IV catheters and endotracheal tubes. We fashioned elegant little chevrons of tape over the wings on our IV catheter hubs (seriously, they had wings) to secure them without obscuring the cannulation site. And we used to tear a one-inch strip of tape longitudinally for a few inches, wrapping one strip around the endotracheal tube and the other across the face like a big mustache.

And then someone would promptly rip our IV or endotracheal tube out while we were loading the patient, so we got to do it again.

Nowadays we have tube holders and IV dressings, and taping is a lost art like calligraphy and darning your socks.

5. Rotating tourniquets
Once upon a time, we used to think that acute pulmonary edema and decompensated congestive heart failure was caused by too much blood re-entering the lungs. We thought that if we could trap blood in the extremities, we'd reduce preload enough to relieve the pulmonary edema.

So we applied humongous blood pressure cuffs on three of the patient's four extremities, inflated them to just above diastolic pressure, and rotated them around the patient's extremities every 15 minutes.

And it took us only a generation or so to discover that it was stupid and didn't work.

4. Trendelenburg position
For many years we fervently believed the Trendelenburg position was a vital treatment for shock. We thought that elevating the feet higher than the head raised blood pressure, and maybe even caused a couple units of blood to flow from the legs to the trunk.

Turns out it doesn't really do those things, and instead caused respiratory decompensation and a rise in intracranial pressure. Still, that doesn't keep some EMTs working for the EMS Agency That Time Forgot from carefully applying and documenting "patient placed in Trendelenburg position."

3. Standing takedowns
Now that our current understanding of spinal cord injury acknowledges that prehospital spinal immobilization on backboards has virtually no supporting evidence and probably does more harm than good, we're boarding far fewer people these days.

While the adage holds true that "absence of evidence does not mean evidence of absence," and there may be some yet-undiscovered tiny subset of patients that benefit from strapping a curved body to a flat board, it's a pretty safe bet that subset does not include people walking around the scene under their own power.

2. External jugular IV access
Honestly, I really miss this one. The EJ used to be my go-to vein in a code. I was already right there at the head intubating, and all it took was turning the patient's head to one side a bit, sinking a 14-gauge in that fat, engorged vein, and you had the mother of all peripheral IV accesses.

You know, we did this so all those questionably beneficial drugs we gave could reach the heart that much faster. Now, with mechanical IO devices like the EZ-IO in my repertoire, I can't remember the last time I started an EJ.

Adult IO devices have really revolutionized emergency peripheral vascular access. And not a moment too soon, either, before this intracavernous technique really caught on.  

1. Radio 10 codes
Once upon a time, we used to take sadistic pleasure in rapid fire broadcasting to the brand-new dispatcher, "Dispatch, we're 10-98, 10-8, 10-19, 10-18 to our 10-42, where we'll be 10-7 for a few minutes for a 10-33 10-100. If we're not 10-2 on that, we'll be happy to 10-9."

Now that we communicate in plain English because 10 codes are confusing and vary between agencies, we get to say, "Dispatch, we've completed our last assignment and are available for call, but we're heading to our station as soon as possible because my partner will be out of service taking an emergency all-he-could-eat taco buffet poop. If you didn't copy all that, I'm willing to repeat it."

Or at least we get to say that once.

I could think of a few more EMT skills that may soon become obsolete if we don't get better at applying them, but that's my list of top 10 obsolete EMT skills.

Got any to add to the list? Chime in with yours in the comments.



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Dual tumor-suppressors miR-139-5p and miR-139-3p targeting matrix metalloprotease 11 (MMP11) in bladder cancer

cover.gif?v=1&s=cd51c7f7da7776e178cb46d5

Abstract

Our recent study of the microRNA (miRNA) expression signature of bladder cancer (BC) by deep-sequencing revealed that two miRNAs, microRNA-139-5p/microRNA-139-3p were significantly downregulated in BC tissues. The aim of this study was to investigate the functional roles of these miRNAs and their modulation of cancer networks in BC cells.

Functional assays of BC cells were performed using transfection of mature miRNAs or small interfering RNAs (siRNAs). Genome-wide gene expression analysis, in silico analysis, and dual-luciferase reporter assays were applied to identify miRNA targets. The associations between the expression of miRNA and its targets and overall survival were estimated by the Kaplan-Meier method. Gain-of-function studies showed that miR-139-5p and miR-139-3p significantly inhibited cell migration and invasion by BC cells. The matrix metalloprotease 11 gene (MMP11) was identified as a direct target of miR-139-5p and miR-139-3p. Kaplan-Meier survival curves showed that higher expression of MMP11 predicted shorter survival of BC patients (P = 0.029). Downregulated miR-139-5p or miR-139-3p enhanced BC cell migration and invasion in BC cells. MMP11 was directly regulated by these miRNAs and might be a good prognostic marker for survival of BC patients.

This article is protected by copyright. All rights reserved.



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Police: Man drowns in agricultural waste

Associated Press

NEWPORT, Pa. — Authorities say a man is dead after a farming accident in central Pennsylvania.

Police say the man had been operating farm equipment Tuesday in Newport when he fell into a reservoir of agricultural waste and drowned.

Newport is about 15 miles north of Harrisburg.

State police and the Perry County Coroner's Office identified the victim as 26-year-old Leon Stump Jr. of Newport.

His death has been ruled an accident.



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Current Strategy for the Treatment of Ovarian Germ Cell Tumors: Role of Extensive Surgery

Current Strategy for the Treatment of Ovarian Germ Cell Tumors: Role of Extensive Surgery:

Opinion Statement

The necessity and extent of comprehensive surgical staging (CSS) and lymphadenectomy in the treatment of malignant ovarian germ cell tumors (MOGCTs) is still controversial. However, it is uniformly agreed that CSS with lymphadenectomy is crucial to follow up patients without adjuvant chemotherapy in stage I MOGCTs. Considering the chemotherapy-sensitive nature of MOGCTs, fertility-sparing cytoreductive surgery (FSCS) seems a reasonable approach in initial treatment for patients with advanced stage. When encountered with bilateral MOGCTs, debulking is surely granted if there is no desire for fertility. Both ovaries completely replaced by neoplastic tissue composed the most challenging situation especially when patients require childbearing potential. In dysgerminoma histology, which usually has good prognosis, residual disease could be left to spare fertility. USO of the largest and more heterogeneous ovarian mass and a biopsy of the contralateral lesion may be considered if the patients are compliant to regular follow-up. NACT followed by interval FSCS may be a reasonable option in patients with extensive disease, when initial debulking is not an option or where the poor general condition or clinical findings suggest an increased risk of surgical morbidity or preclude fertility-sparing surgery. This is currently not the standard of care but deserves future study. In some rare situation, when any remaining ovarian tissue means high risk, BSO may be performed with the uterus preserved for possible assisted reproduction with donor egg. Treatment failure occurs in a small group of MOGCTs after primary treatment. A good number of recurrences can be salvaged with selected salvage surgery, especially when optimal secondary cytoreduction can be achieved. Immature teratoma is a subtype of MOGCTs where secondary cytoreduction may have a strong role to play.

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Dual tumor-suppressors miR-139-5p and miR-139-3p targeting matrix metalloprotease 11 (MMP11) in bladder cancer

Dual tumor-suppressors miR-139-5p and miR-139-3p targeting matrix metalloprotease 11 (MMP11) in bladder cancer:

Abstract

Our recent study of the microRNA (miRNA) expression signature of bladder cancer (BC) by deep-sequencing revealed that two miRNAs, microRNA-139-5p/microRNA-139-3p were significantly downregulated in BC tissues. The aim of this study was to investigate the functional roles of these miRNAs and their modulation of cancer networks in BC cells.

Functional assays of BC cells were performed using transfection of mature miRNAs or small interfering RNAs (siRNAs). Genome-wide gene expression analysis, in silico analysis, and dual-luciferase reporter assays were applied to identify miRNA targets. The associations between the expression of miRNA and its targets and overall survival were estimated by the Kaplan-Meier method. Gain-of-function studies showed that miR-139-5p and miR-139-3p significantly inhibited cell migration and invasion by BC cells. The matrix metalloprotease 11 gene (MMP11) was identified as a direct target of miR-139-5p and miR-139-3p. Kaplan-Meier survival curves showed that higher expression of MMP11 predicted shorter survival of BC patients (P = 0.029). Downregulated miR-139-5p or miR-139-3p enhanced BC cell migration and invasion in BC cells. MMP11 was directly regulated by these miRNAs and might be a good prognostic marker for survival of BC patients.

This article is protected by copyright. All rights reserved.

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Current Strategy for the Treatment of Ovarian Germ Cell Tumors: Role of Extensive Surgery

Opinion Statement

The necessity and extent of comprehensive surgical staging (CSS) and lymphadenectomy in the treatment of malignant ovarian germ cell tumors (MOGCTs) is still controversial. However, it is uniformly agreed that CSS with lymphadenectomy is crucial to follow up patients without adjuvant chemotherapy in stage I MOGCTs. Considering the chemotherapy-sensitive nature of MOGCTs, fertility-sparing cytoreductive surgery (FSCS) seems a reasonable approach in initial treatment for patients with advanced stage. When encountered with bilateral MOGCTs, debulking is surely granted if there is no desire for fertility. Both ovaries completely replaced by neoplastic tissue composed the most challenging situation especially when patients require childbearing potential. In dysgerminoma histology, which usually has good prognosis, residual disease could be left to spare fertility. USO of the largest and more heterogeneous ovarian mass and a biopsy of the contralateral lesion may be considered if the patients are compliant to regular follow-up. NACT followed by interval FSCS may be a reasonable option in patients with extensive disease, when initial debulking is not an option or where the poor general condition or clinical findings suggest an increased risk of surgical morbidity or preclude fertility-sparing surgery. This is currently not the standard of care but deserves future study. In some rare situation, when any remaining ovarian tissue means high risk, BSO may be performed with the uterus preserved for possible assisted reproduction with donor egg. Treatment failure occurs in a small group of MOGCTs after primary treatment. A good number of recurrences can be salvaged with selected salvage surgery, especially when optimal secondary cytoreduction can be achieved. Immature teratoma is a subtype of MOGCTs where secondary cytoreduction may have a strong role to play.



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Dual tumor-suppressors miR-139-5p and miR-139-3p targeting matrix metalloprotease 11 (MMP11) in bladder cancer

cover.gif?v=1&s=cd51c7f7da7776e178cb46d5

Abstract

Our recent study of the microRNA (miRNA) expression signature of bladder cancer (BC) by deep-sequencing revealed that two miRNAs, microRNA-139-5p/microRNA-139-3p were significantly downregulated in BC tissues. The aim of this study was to investigate the functional roles of these miRNAs and their modulation of cancer networks in BC cells.

Functional assays of BC cells were performed using transfection of mature miRNAs or small interfering RNAs (siRNAs). Genome-wide gene expression analysis, in silico analysis, and dual-luciferase reporter assays were applied to identify miRNA targets. The associations between the expression of miRNA and its targets and overall survival were estimated by the Kaplan-Meier method. Gain-of-function studies showed that miR-139-5p and miR-139-3p significantly inhibited cell migration and invasion by BC cells. The matrix metalloprotease 11 gene (MMP11) was identified as a direct target of miR-139-5p and miR-139-3p. Kaplan-Meier survival curves showed that higher expression of MMP11 predicted shorter survival of BC patients (P = 0.029). Downregulated miR-139-5p or miR-139-3p enhanced BC cell migration and invasion in BC cells. MMP11 was directly regulated by these miRNAs and might be a good prognostic marker for survival of BC patients.

This article is protected by copyright. All rights reserved.



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Phosphorylated-insulin growth factor I receptor (p-IGF1R) and metalloproteinase-3 (MMP3) expression in advanced gastrointestinal stromal tumors (GIST). A GEIS 19 study

Abstract

Background

Most GISTs have mutations in KIT or PDGFRA. Patients with advanced GIST with KIT exon 9, PDGFRA mutation or WT for KIT and PDGFRA have a worse progression-free survival (PFS) compared to patients with KIT exon 11 mutated tumors. We evaluated the immunohistochemical (IHC) expression of p-IGF1R (Y1316) and MMP3 as predictors of PFS or overall survival (OS).

Methods

Ninety-two advanced GIST patients included in GEIS-16 study with KIT and PDGFRA mutational information were examined for p-IGF1R (Y1316) and MMP3 expression in a tissue micro-array. To study activation of the IGF1R system, we have used an antibody (anti-pY1316) that specifically recognizes the active phosphorylated form of the IGF1R. DNA was extracted from paraffin-embedded tissues and intronic PCR primers were used to amplify exons 9, 11, 13 and 17 of KIT, 12 and 18 of PDGFRA. Bidirectional sequencing with specific primers was performed on a ABI3100 sequencer using the Big Dye Terminator v3.1 kit. Multivariate model was built using a stepwise automated variable selection approach with criterion to enter the variable in the model of p < 0.10 and criterion to keep the variable in the model of p < 0.05. PFS was computed as the date of imatinib initiation to progression or death. Overall survival was defined as the time from imatinib initiation to death.

Results

Phospho-IGF1R was expressed only in 9 % (2/22) of cases without KIT mutation. MMP3 expression was detected in 2/5 patients (40 %) with PDGFRA mutation, 1/16 patients (6 %) with WT genotype and 7/71 patients (10 %) of KIT mutant patients. At univariate analysis KIT exon 11/13 mutation had better PFS than patients with exon 9 mutation, PDGFRA mutation or WT genotype (p = 0.021; HR: 0.46; 95 %CI (0.28–0.76). Less than 24 months disease free-interval (HR 24.2, 95 % CI 10.5–55.8), poor performance status (PS) (HR 6.3, 95 % CI 2.5–15.9), extension of disease; >1 organ (HR 1.89; 95 % CI 1.03–3.4) and genotype analysis (HR 0.57, 95 % CI 0.37–0.97) but not immunophenotype analysis (HR 1.53; 95 % CI 0.76–3.06) were the strongest prognostic factors for PFS in the multivariate analysis.

Conclusions

Our results do not support p-IGF-1R and MMP3 evaluation in non-selected GIST patients but evaluation of this immunophenotype in WT and mutant PDGFR mutation in larger group of GIST patients, deserve merits.



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