Τρίτη 20 Απριλίου 2021

Phosphorylation of MYL12 by Myosin Light Chain Kinase Regulates Cellular Shape Changes in Cochlear Hair Cells

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Abstract

The organ of Corti is an auditory organ located in the cochlea, comprising hair cells (HCs) and other supporting cells. Cellular shape changes of HCs are important for the development of auditory epithelia and hearing function. It was previously observed that HCs and inner sulcus cells (ISCs) demonstrate cellular shape changes similar to the apical constriction of the neural epithelia. Apical constriction is induced via actomyosin cable contraction in the apical junctional complex and necessary for the physiological function of the epithelium. Actomyosin cable contraction is mainly regulated by myosin regulatory light chain (MRLC) phosphorylation by myosin light chain kinase (MLCK). However, MRLC and MLCK isoforms expressed in HCs and ISCs are unknown. Hence, we investigated the expression patterns and roles of MRLCs and MLCKs in HCs. Droplet digital PCR revealed that HCs expressed MYL12A/B and MYL9, which are non-muscle MRLC and smooth muscle MLCK (smMLCK), resp ectively. Immunofluorescence staining throughout the organ of Corti demonstrated that only MYL12 was expressed in the apical portion of HCs, whereas MYL12 and MYL9 were expressed on ISCs. In addition, purified MYL12B was phosphorylated by smMLCK in vitro, and the harvested HCs contained phosphorylated MYL12. Furthermore, accompanied by the expansion of the cell area of outer HCs, MYL12 phosphorylation was reduced by ML-7, which is an inhibitor of smMLCK. In conclusion, MYL12 phosphorylation by smMLCK contributed to the apical constriction-like cellular shape change of HCs possibly relating to the development of auditory epithelia and hearing function.

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Age and cancer treatment factors influence patient-reported outcomes following therapeutic mammoplasty and contralateral symmetrisation for the treatment of breast cancer

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J Plast Reconstr Aesthet Surg. 2021 Mar 28:S1748-6815(21)00121-2. doi: 10.1016/j.bjps.2021.03.031. Online ahead of print.

ABSTRACT

BACKGROUND: Oncoplastic surgery for breast cancer has increased in popularity over the last few years, with oncological safety confirmed in several studies. There are, however, limited published data on patient-reported outcomes from this surgical approach. This study assessed patient-reported outcomes of satisfaction following therapeutic mammoplasty and contralateral symmetrisation (TMCS) as part of breast cancer treatment in relation to other patient and treatment factors.

METHODS: The validated BREAST-Q™ breast reduction module was sent to all surviving patients who had no documented cancer recurrence and had undergone TMCS in NHS Tayside between August 2013 and August 2017. The Q-score was used to analyse data and correlate with patient clinical information, surgical, pathology and treatment fa ctors. Ethical approval was granted by the University of Dundee ethics committee.

RESULTS: The patient response rate to the study was 64.5% (60 of 93 patients), with a mean age of 59 years (range 41-75 years). In all domains, patients reported high levels of satisfaction with outcomes. There were strong correlations between domains with the exception of physical symptoms. Younger patients reported poorer outcomes in domains that related to satisfaction with outcomes of surgery, psychosocial aspects, sexual function and physical symptoms. Treatment with chemotherapy and/or trastuzumab and lymph node positivity were associated with poorer outcomes in a number of domains.

CONCLUSIONS: Our results demonstrate that patients report high levels of satisfaction after TMCS, but this is influenced by age. Patient-reported outcomes that include physical and psychosocial appear to be more strongly influenced by medical treatments than surgery.

PMID:33875389 | DOI:10.1016/j.bjps.2021.03.031

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Intracranial arachnoid cysts and epilepsy in children: Should this be treated surgically? Our 29-year experience and review of the literature

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Neurocirugia (Astur). 2021 Apr 16:S1130-1473(21)00033-6. doi: 10.1016/j.neucir.2021.03.003. Online ahead of print.

ABSTRACT

INTRODUCTION AND OBJECTIVE: Arachnoid cysts (ACs) are relatively frequent lesions related to different neurological symptoms, being mostly incidentally diagnosed. This study aims to clarify whether AC surgery in epileptic patients is useful in their treatment.

MATERIAL AND METHODS: The patients registered in the database of the Neuropediatrics Section from May 1990 to August 2019 are analyzed retrospectively. Patients in whom the diagnosis of ACs and epilepsy coincide are studied. The location, size and number of ACs, neurological development, age at diagnosis, follow-up time, the performance of surgery on the cyst, evolution, anatomical relationship between brain electrical activity and location of AC, and type of epilepsy are analyzed.

RESULTS: After analyzing the database, we found 1881 patients diagnosed with epilepsy, of which 25 had at least one intracranial AC. In 9 of the patients, cerebral or genetic pathologies were the cause of epilepsy. Of the other 16, only 2 patients showed that the type of epilepsy and the epileptogenic focus coincided with the location of the AC; one of them was surgically treated without success, and the other one remained asymptomatic without receiving medical or surgical treatment.

CONCLUSIONS: Although it is necessary to design a prospective study to establish causality, the results of our research and the available literature suggest that there is no causal relationship between the presence of ACs and epilepsy. The study and treatment of these patients should be carried out in a multidisciplinary epilepsy surgery unit, without initially assuming that the AC is the cause of epilepsy.

PMID:33875379 | DOI:10.1016/j.neucir.2021.03.003

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Prognostic value of the pulse pressure amplitudes, time to reach the plateau and the slope obtained in the lumbar infusion test for the study of idiophatic normal pressure hydrocephalus

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Neurocirugia (Astur). 2021 Apr 16:S1130-1473(21)00030-0. doi: 10.1016/j.neucir.2021.02.004. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: To study the prognostic value of the resistance to the cerebrospinal fluid outflow (Rout) obtained in the lumbar infusion test in idiopathic normal pressure hydrocephalus (iNPH), as well as the pulse pressure amplitudes in the different periods of the test and other new variables extracted by Neuropicture® software.

MATERIAL AND METHODS: Patients with ́probable iNPH́ who underwent a lumbar infusion test were retrospectively revised. The positive predictive values (PPV) of the cutoff point of the best prognostic accuracy of the Rout, the basal pulse pressure amplitude (AMP0), the pulse pressure amplitude during the first 10minutes (AMP10min), the plateau pulse pressure amplitude (AMPmes), the Rout pulse pressure amplitude (AMPRout), the time to reach the plateau (T) , and the slope until reaching the plateau were determined. Patients were categorized either as responders or non-responders.

RESULTS: The study included 64 responders patients and 16 non-responders patients. The PPV of Rout> 15mmHg/ml/min was 91.7%; AMP0> 2.34mmHg: 91.3%; AMP10min>4.34mmHg: 83.3%; AMPmes>12.44mmHg: 84.6%; AMPRout>6.34mmHg: 85%; T <634seconds: 86.7%; P>0.040mmHg/sec: 96.3%.

CONCLUSIONS: Rout is a valid criterion to indicate a ventricular shunt. Pulse pressure amplitudes in the different periods of the lumbar infusion test, in addition to T and P, are other variables whose positivity is indicative of shunt response and should be considered in the diagnostic protocol of the iNPH.

PMID:33875381 | DOI:10.1016/j.neucir.2021.02.004

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Myxofibrosarcoma: Another mimicker of meningioma

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Neurocirugia (Astur). 2021 Apr 16:S1130-1473(21)00032-4. doi: 10.1016/j.neucir.2021.03.002. Online ahead of print.

ABSTRACT

Primary intracranial malignant fibrous histiocytoma (MFH), or myxofibrosarcoma, is an extremely rare condition, with only a few cases reported in the literature. We report a case of a dural-based myxofibrosarcoma in a previously healthy 42-year-old man that was initially presumed to be an atypical meningioma. The findings based on conventional and advanced magnetic resonance sequences, including diffusion-weighted imaging, perfusion weighted imaging and proton magnetic resonance spectroscopy, as well as histopathological aspects, are discussed.

PMID:3387 5380 | DOI:10.1016/j.neucir.2021.03.002

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Need for head and neck repositioning to restore electrophysiological signal changes at positioning for cervical myelopathy surgery

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Neurocirugia (Astur). 2021 Apr 16:S1130-1473(21)00031-2. doi: 10.1016/j.neucir.2021.03.001. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the incidence of significant intraoperative electrophysiological signal changes during surgical positioning, and to assess the effectiveness of head and neck repositioning on the restoration of signals, among patients undergoing surgery for cervical myelopathy.

MATERIAL AND METHODS: We used multimodal intraoperative monitoring (somatosensory [SEP] and motor evoked potentials [MEP] and spontaneous electromyography) before and after patients' positioning in a consecutive cohort of 103 patients operated for symptomatic cervical myelopathy. Significant changes were defined as>50% attenuation in amplitude or>10% increase in latency of SEP, or abolishment or 50-80% attenuation of MEP.

RESULTS: Out of 103 patients (34.9% female, median age 54.5 years) 88 underwent laminectomy (85.4%) and 15 (14.6%) anterior approach. At the time of positioning, signal alterations occurred in 44 patients (42.7%), yet only 11 patients (10.7%) showed alarming changes. Immediate neck repositioning of these resulted in complete (n=6) or partial (n=4) restoration of potentials, yielding no postoperative deficits. The patient in which signals could not be restored after repositioning resulted in added postoperative deficit. The accuracy (true positives plus true negatives) of monitoring to detect new neurological deficits was 99.0% (102/103) for the entire cohort, and 100% (11/11) for those showing significant changes at the moment of positioning. Overall, only 1 patient, with non-significant SEP attenuation, experienced a new postoperative deficit, yielding a 0.97% rate of false negatives.

CONCLUSION: Among patients undergoing surgery for cervical myelopathy, 10.7% showed alarming electrophysiological signal changes at the time of positioning. Immediate repositioning of the neck re sulted in near always restoration of potentials and avoidance of added neurological damage. Complete or partial restoration of potentials after repositioning yielded no postoperative deficits.

PMID:33875378 | DOI:10.1016/j.neucir.2021.03.001

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Downregulation of Caveolin-1 and Upregulation of Deiodinase 3, Associated with Hypoxia-Inducible Factor-1α Increase, Are Involved in the Oxidative Stress of Graves' Orbital Adipocytes

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Thyroid, Volume 31, Issue 4, Page 627-637, April 2021.
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Seltener Tumor im Oberlid

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Laryngorhinootologie
DOI: 10.1055/a-1475-5121



Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Therapie von Sprachentwicklungsstörungen: Eine Leitlinie ist längst überfällig

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Laryngorhinootologie
DOI: 10.1055/a-1408-7599

Für die Therapie von Sprachentwicklungsstörungen (SES) ist bislang weitgehend unklar, wie die Evidenz aus individueller therapeutischer Expertise in das klinisch-praktische Vorgehen integriert wird. Die Entwicklung einer Leitlinie zur Therapie von SES, insbesondere für Kindergarten- und Vorschulkinder, ist daher aus 2 Gründen längst überfällig und zugleich eine besondere Herausforderung: (1) SES, die nicht im Zusammenhang mit einer Komorbidität stehen, werden mit verschiedenen Termini belegt und (2) bilden alle SES eine Schnittstelle medizinischer, psychologischer, pädagogischer, linguistischer und sprachtherapeutischer Fachdisziplinen. Die Deutsche Gesellschaft für Phoniatr ie und Pädaudiologie hat nun eine „Interdisziplinäre (S3-) Leitlinie zur Therapie von Sprachentwicklungsstörungen" (Register-Nr. 049–015) bei der Arbeitsgemeinschaft Wissenschaftlicher Medizinischer Fachgesellschaften AWMF e. V. angemeldet. Damit soll die Lücke zwischen sprachtherapeutischer Praxis und Forschungsevidenz geschlossen werden, um für den individuellen Behandlungsfall eine möglichst optimale Therapieempfehlung bzw. Therapieentscheidung treffen zu können – basierend auf dem besten wissenschaftlich verfügbaren Fachwissen.
[...]

Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of conte nts  |  Abstract  |  Full text

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β-Ecdysone attenuates cartilage damage in a mouse model of collagenase-induced osteoarthritis via mediating FOXO1/ADAMTS-4/5 signaling axis

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Histol Histopathol. 2021 Apr 20:18341. doi: 10.14670/HH-18-341. Online ahead of print.

ABSTRACT

BACKGROUND: β-Ecdysone has been reported to perform a protective effect to prevent interleukin 1β (IL-1β)-induced apoptosis and inflammatory response in chondrocytes. In our study, the chondroprotective effects of β-Ecdysone were explored in a mouse model of collagenase-induced osteoarthritis (OA).

METHODS: Injection of collagenase in the left knee was implemented to establish a mouse model of OA. The histomorphological analysis was detected using safranine O staining. Serum pro-inflammatory cytokines were measured by ELISA assays. Protein expression in the femur and chondrocytes was analyzed using western blot. Chondrocyte apoptosis was evaluated by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining.

RESULTS: Treatment of OA mice with β-Ecdysone supplementation significantly inhibited the pro duction of pro-inflammatory cytokines. Histologic examination exhibited that the degradation of proteoglycans and the loss of trabecular bone were observed in collagenase-injected mice. However, OA-like changes were attenuated by β-Ecdysone administration in collagenase-injected mice. Both in vivo and in vitro models, nuclear forkhead box O1 (FOXO1) protein expression was significantly reduced in the femur of collagenase-treated mice and IL-1β-stimulated chondrocytes. However, β-Ecdysone treatment was able to rescue FOXO1 protein expression in the nucleus to inhibit the transcription and translation of a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 4 (ADAMTS-4) and ADAMTS-5.

CONCLUSION: The findings suggested that β-Ecdysone functioned as a FOXO1 activator to protect collagenase-induced cartilage damage. FOXO1 might be a potential molecular target of β-Ecdysone for the effective prevention and treatment of OA.

PMID:33876419 | DOI:10.14670/HH-18-341

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Prognostic Factors for the Outcome of Salivary Gland Holmium: YAG Laser Intraductal Lithotripsy

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Ear Nose Throat J. 2021 Apr 20:1455613211010075. doi: 10.1177/01455613211010075. Online ahead of print.

ABSTRACT

OBJECTIVES: Holmium: YAG laser has gained its popularity throughout the years and is used to treat sialolithiasis, which helps to overcome the limitations of traditional sialendoscopic lithotripsy for larger-sized salivary stones. However, little information is available regarding factors predicting the success rate of Holmium: YAG laser intraductal lithotripsy. T he purpose of this study is to investigate the factors affecting the success rates of Holmium: YAG laser lithotripsy for salivary stones treatment in a tertiary care hospital.

METHODS: A retrospective study conducted in patients receiving sialolithiasis surgery under sialendoscopy from May 2013 to March 2015 at Mackay Memorial Hospital, Taiwan. Data on various factors, including patients' age, gender, glands, size of largest stone, multiple stones (≥2 stones), location of the stone (distal duct, middle duct, proximal duct, and hilum), and operative time. The success of the surgery defined as patients without any complaints such as swelling or tenderness. Logistic regression and Fisher exact tests were employed to examine these factors on the success rate.

RESULTS: Fifty-four patients who received sialendoscopy surgery with a mean age of 35.74 years old recruited. Logistic regression identified the operation time exceeding 210 minutes showed 23.497 folds higher odd rati o of having a result of operation failure (P < .05).

CONCLUSION: The prolonged operation time is the sole independent factor affecting the successful outcome for salivary gland intraductal laser lithotripsy. We recommend operative time be no more than 210 minutes to increase the success rate in salivary gland Holmium: YAG laser intraductal lithotripsy.

PMID:33877921 | DOI:10.1177/01455613211010075

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