Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Κυριακή 9 Ιουλίου 2017

Therapeutic experience with oral finasteride for androgenetic alopecia in female-to-male transgender patients

Summary

Background

Androgenic treatment of female-to-male transgender patients may result in androgenetic alopecia (AGA). Use of 5-alpha-reductase inhibitors are useful as oral treatment of AA in men. There are no previous studies of the use of finasteride in transgender men as treatment of AGA.

Aim

To evaluate the effectiveness and safety of an oral 5α-reductase inhibitor (finasteride) for AA developed in transgender men.

Methods

This single-centre retrospective study enrolled female-to-male transgender patients with a clinical diagnosis of AGA to receive 1 mg of an oral type II 5α-reductase inhibitor for at least 12 months.

Results

In all, 10 patients were included in the study. All the patients received a clinical diagnosis of male-pattern AGA, with 90% classified as stage IV on the Norwood-Hamilton scale. Mean onset of AGA was 3.25 years after the introduction of androgenic treatment, and 70% of the patients had a family history of AGA. All the patients improved one grade on the Norwood–Hamilton scale after a mean of 5.5 months (range 4–6 months) since the start of finasteride treatment. Two patients stopped treatment for economic reasons and one stopped due to dyspepsia. No sexual or other adverse effects were observed. Patients were given periodic physical and analytical examinations by endocrinologists without any significant finding. Mean follow-up of patients was 16.2 months.

Conclusion

AA in transgender men has a delayed onset, and is clinically and therapeutically similar to the common male-pattern-AGA in cis-gender men.



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Seabather's eruption caused by the thimble jellyfish (Linuche aquila) in the Philippines



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Complex autonomic pathways in patients with idiopathic hyperhidrosis



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Clarithromycin, rifampicin and fusidic acid triple combination therapy for chronic folliculocentric pustulosis of the scalp



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Serial D-dimer plasma levels in a patient with chronic spontaneous urticaria developing resistance to omalizumab

Summary

Chronic spontaneous urticaria (CSU) is a condition presenting as the spontaneous occurrence of itchy weals with or without angio-oedema for > 6 weeks. A patient with severe chronic spontaneous urticaria who developed resistance to omalizumab is described. The patient's D-dimer plasma levels strictly paralleled the disease activity despite the administration of anti-IgE therapy.



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Comprehensive profiling of H-Ras signalling in angiosarcoma endothelium

Summary

The MS1/SVR system, in which MS1 represents immortalized endothelial cells and SVR represents MS1 cells transformed with oncogenic human–rat sarcoma protein (H-Ras), has been used for around 20 years as a valuable tool to study angiogenesis and carcinogenesis. Despite the use of these cells in numerous studies, a comprehensive profile of the signalling differences due to oncogenic H-Ras transformation has not been performed previously. In this study, we profiled the well-known MS1 and SVR cell lines using a combination of both Western blot and gene chip assays.



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Acquired reactive perforating collagenosis associated with Hodgkin disease



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Systemic lupus erythematosus, following prodromal idiopathic thrombocytopenic purpura, presenting with skin lesions resembling malignant atrophic papulosis

Summary

Systemic lupus erythematosus (SLE) is an autoimmune disease. Its incidence in the UK is approximately 1 per 10 000. Cutaneous involvement, encompassing acute, subacute and chronic disease, occurs in over two-thirds of cases, and can often be the first clue to diagnosis. We describe a highly unusual case of SLE occurring after prodromal idiopathic thrombocytopenic purpura (ITP) and presenting with skin lesions more typical of malignant atrophic papulosis, a rare and often fatal vasculopathy. Such a combination of rare features emphasizes the potential for complexity in this multisystem disease.



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Peanut allergy and isotretinoin: reply to McCarthy et al.



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Treatment of paediatric facial pyogenic granuloma with topical ingenol mebutate



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Eruptive vellus hair cysts of the vulva



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Endothelial cells: From innocent bystanders to active participants in immune responses

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Publication date: Available online 8 July 2017
Source:Autoimmunity Reviews
Author(s): A. Al-Soudi, M.H. Kaaij, S.W. Tas
The endothelium is crucially important for the delivery of oxygen and nutrients throughout the body under homeostatic conditions. However, it also contributes to pathology, including the initiation and perpetuation of inflammation. Understanding the function of endothelial cells (ECs) in inflammatory diseases and molecular mechanisms involved may lead to novel approaches to dampen inflammation and restore homeostasis. In this article, we discuss the various functions of ECs in inflammation with a focus on pathological angiogenesis, attraction of immune cells, antigen presentation, immunoregulatory properties and endothelial-to-mesenchymal transition (EndMT). We also review the current literature on approaches to target these processes in ECs to modulate immune responses and advance anti-inflammatory therapies.



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Circulating CXCL10 is increased in non-segmental vitiligo, in presence or absence of autoimmune thyroiditis

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Publication date: Available online 8 July 2017
Source:Autoimmunity Reviews
Author(s): Silvia Martina Ferrari, Poupak Fallahi, Giulia Santaguida, Camilla Virili, Ilaria Ruffilli, Francesca Ragusa, Marco Centanni, Alessandro Antonelli
Recently the importance of CXCL10 in the pathogenesis of non-segmental vitiligo (NSV) and autoimmune thyroid disorders (AITD) has been shown. No data are present about chemokines CXCL10 (Th1 prototype) and CCL2 (Th2 prototype) circulating levels in NSV patients with/without thyroiditis (AT).Serum CXCL10 and CCL2 have been measured in 50 consecutive NSV patients, in 40 consecutive patients with NSV and AT (NSV+AT), in 50 sex- and age-matched controls without AT (control 1) and in 40 sex- and age-matched patients with AT without NSV (control 2).Serum CXCL10 levels were significantly higher in control 2, than in control 1 (P=0.001; ANOVA). NSV patients have serum CXCL10 levels significantly higher than control 1, or control 2 (P=0.001). NSV+AT patients have serum CXCL10 levels higher than control 1, or 2 (P<0.001), and than NSV (P=0.01).In conclusion, we first demonstrate high serum CXCL10 in NSV patients, overall in presence of AT and hypothyroidism, suggesting the importance of a common Th1 immune response in their immune-pathogenesis. To evaluate if serum CXCL10 might be used as a clinical marker of NSV and/or AT further studies are needed.



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Biomarkers of disease activity in vitiligo: A systematic review

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Publication date: Available online 8 July 2017
Source:Autoimmunity Reviews
Author(s): R. Speeckaert, M. Speeckaert, S. De Schepper, N. van Geel
The pathophysiology of vitiligo is complex although recent research has discovered several markers which are linked to vitiligo and associated with disease activity. Besides providing insights into the driving mechanisms of vitiligo, these findings could reveal potential biomarkers. Activity markers can be used to monitor disease activity in clinical trials and may also be useful in daily practice. The aim of this systematic review was to document which factors have been associated with vitiligo activity in skin and blood. A second goal was to determine how well these factors are validated in terms of sensitivity and specificity as biomarkers to determine vitiligo activity. Both in skin (n=42) as in blood (n=66) an adequate number of studies fulfilled the predefined inclusion criteria. These studies used diverse methods and investigated a broad range of plausible biomarkers. Unfortunately, sensitivity and specificity analyses were scarce. In skin, simple histopathology with or without supplemental CD4 and CD8 stainings can still be considered as the gold standard, although more recently chemokine (C-X-C motif) ligand (CXCL) 9 and NLRP1 have demonstrated a good and possibly even better association with progressive disease. Regarding circulating biomarkers, cytokines (IL-1β, IL-17, IFN-γ, TGF-β), autoantibodies, oxidative stress markers, immune cells (Tregs), soluble CDs (sCD25, sCD27) and chemokines (CXCL9, CXCL10) are still competing. However, the two latter may be preferable as both chemokines and soluble CDs are easy to measure and the available studies display promising results. A large multicenter study could make more definitive statements regarding their sensitivity and specificity.



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Spasticity in multiple sclerosis: Contribution of inflammation, autoimmune mediated neuronal damage and therapeutic interventions

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Publication date: Available online 8 July 2017
Source:Autoimmunity Reviews
Author(s): Robert Patejdl, Uwe K. Zettl
In contrast to other diseases that go along with spasticity (e.g. spinal cord injury), spasticity in chronic autoimmune diseases involving the CNS is complicated by the ongoing damage of neuronal networks that leads to permanent changes in the clinical picture of spasticity.Multiple sclerosis (MS) is the most frequent autoimmune disease of the central nervous system (CNS) and spasticity is one of the most disabling symptoms. It occurs in more than 80% MS patients at some point of the disease and is associated with impaired ambulation, pain and the development of contractures.Besides causing cumulative structural damage, neuroinflammation occurring in MS leads to dynamic changes in motor circuit function and muscle tone that are caused by cytokines, prostaglandins, reactive oxygen species and stress hormones that affect neuronal circuits and thereby spasticity.The situation is complicated further by the fact that therapeutics used for the immunotherapy of MS may worsen spasticity and drugs used for the symptomatic treatment of spasticity have been shown to have the potential to alter immune cell function and CNS autoimmunity itself. This review summarizes the current knowledge on the immunologic pathways that are involved in the development, maintenance, dynamic changes and pharmacological modulation of spasticity in MS.



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Does type-I interferon drive systemic autoimmunity?

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Publication date: Available online 8 July 2017
Source:Autoimmunity Reviews
Author(s): Cécile Picard, Alexandre Belot
Type-I interferon (IFN)-mediated immune response involves both innate and adaptive immune system and has a pivotal role in antiviral defence. A complex interplay of intracellular signaling pathways and tight regulatory systems drive the IFN activation. The observation of an aberrant stimulation of this system as a common molecular basis in peculiar inherited autoimmune and autoinflammatory disorders led to the concept of "type I interferonopathies". But the precise genetic dissection of this growing spectrum of diseases adds more and more complexity to the comprehension of this concept and a lot of unsolved questions remain such as how type I IFN can drive systemic inflammation in these clinically and genetically heterogeneous diseases.



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Bile Acids and Intestinal Microbiota in Autoimmune Cholestatic Liver Diseases

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Publication date: Available online 8 July 2017
Source:Autoimmunity Reviews
Author(s): You Li, Ruqi Tang, Patrick S.C. Leung, M. Eric Gershwin, Xiong Ma
Cholestatic liver diseases, including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), are manifested as an impairment of normal bile flow and excessive accumulation of potentially toxic bile acids. Endogenous bile acids are involved in the pathogenesis and progression of cholestasis. Consequently, chronic cholestasis affects the expression of bile acids transporters and nuclear receptors, and results in liver injury. Several lines of evidence suggest that intestinal microbiota plays an important role in the etiopathogenesis of cholestatic liver diseases by regulating metabolism and immune responses. However, progression of the disease may also affect the composition of gut microbiota, which in turn exacerbates the progression of cholestasis. In addition, the interaction between intestinal microbiota and bile acids is not unidirectional. Bile acids can shape the gut microbiota community, and in turn, intestinal microbes are able to alter bile acids pool. In general, gut microbiota actively communicate with bile acids, and together play an important role in the pathogenesis of PBC and PSC. Targeting the link between bile acids and microbiota offers exciting new perspectives for the treatment of those cholestatic liver diseases. This review highlights current understanding of the interactions between bile acids and intestinal microbiota and their roles in cholestatic liver diseases. Further, we postulate a bile acids-intestinal microbiota-cholestasis triangle, in the pathogenesis of cholestatic liver diseases and potential therapeutic strategies by targeting this triangle.



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New Onset Insomnia in a Pediatric Patient: A Case of Anti-NMDA Receptor Encephalitis

Anti-NMDAR encephalitis is becoming more widely recognized as a cause of encephalopathy in both adults and children. Certain clinical features such as mood lability, movement disorders, speech dysfunction, seizures, and autonomic instability in a pediatric patient should prompt immediate concern and evaluation for autoimmune encephalitis among providers. We present the case of a pediatric patient with anti-NMDAR encephalitis in which the symptom prompting medical evaluation was insomnia. Insomnia has not previously been emphasized in the literature as a presenting feature of this disease in children and has a broad differential. Recognition of the symptoms of anti-NMDAR encephalitis and its variable presentation are key to early diagnosis and prompt initiation of treatment which may help to improve outcomes.

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Outcome, Pain Perception, and Health-Related Quality of Life in Patients Submitted to Percutaneous Ethanol Injection for Simple Thyroid Cysts

Thyroid cysts are usually benign lesions that when voluminous may induce cosmetic concerns or local discomfort. Percutaneous ethanol injection (PEI) has been demonstrated to be effective for shrinkage of such cysts. In this retrospective study, we evaluated the efficacy, pain perception, and health-related quality of life (HRQL) in patients submitted to PEI for pure cystic lesions. We reviewed the data of 101 patients who underwent ≤3 PEI. In the whole group of patients, the volume reduction was 66% after the first, 74.4% after the second, and 79.4% after the third PEI treatment. 55.4% had a cystic volume ≤ 10 ml; 85.7% of cysts ≤ 10 ml were cured by just one PEI. The number of PEI was significantly higher in the >30.0 ml group; this latter group obtained the smallest percent reduction versus baseline after the first PEI when compared with smaller cysts. The sensation of pain reported during PEI was absent in 78.3% of cases, and HRQL significantly improved from pre- to the posttreatment. PEI is a safe and effective technique for pure cystic lesions. In addition, HRQL significantly improves, providing a further support for this procedure.

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Influence of the RPL34 gene on the growth and metastasis of oral squamous cell carcinoma cells

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Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Jing Dai, Wei Wei
BackgroundOral squamous cell carcinoma (OSCC) accounts for almost 3% of all malignant tumors all over the world. This study aims to investigate the correlation of RPL34 with the cell growth and metastasis of oral squamous cell carcinoma (OSCC) as well as its clinical prognosis.MethodQuantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry were conducted to determine the RPL34 expression in 85 OSCC tissues and 30 normal oral mucosa tissues. Besides, OSCC cell lines SCC-4 were divided into blank group, negative control (NC) group and RPL34-shRNA group. The qRT-PCR and western blot were performed to measure RPL34 expression, CCK-8 and flow cytometry to observe cell growth and apoptosis, and wound healing and transwell to detect cell migration and invasion.ResultsThe RPL34 gene expression was up-regulated in OSCC tissues and cells. The RPL34 expression was significantly correlated with differentiation degree, TNM stage and lymph node metastasis. Patients with positive RPL34 expression had a poorer prognosis. After inhibition of RPL34 expression, the proliferation of SCC-4 cells was slowed down at 24h, 48h, 72h and 96h respectively, and both the migration distance and the number of invasive cells were reduced, while there was an increase in the ratio of cells at G0/G1 stage and cell apoptosis.ConclusionThe RPL34 gene was highly expressed in OSCC, while silencing RPL34 could block cell proliferation and metastasis, but promote cell apoptosis, suggesting the RPL34 gene to be a new promising clinical target for OSCC therapy.



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Influence of the RPL34 gene on the growth and metastasis of oral squamous cell carcinoma cells

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Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Jing Dai, Wei Wei
BackgroundOral squamous cell carcinoma (OSCC) accounts for almost 3% of all malignant tumors all over the world. This study aims to investigate the correlation of RPL34 with the cell growth and metastasis of oral squamous cell carcinoma (OSCC) as well as its clinical prognosis.MethodQuantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry were conducted to determine the RPL34 expression in 85 OSCC tissues and 30 normal oral mucosa tissues. Besides, OSCC cell lines SCC-4 were divided into blank group, negative control (NC) group and RPL34-shRNA group. The qRT-PCR and western blot were performed to measure RPL34 expression, CCK-8 and flow cytometry to observe cell growth and apoptosis, and wound healing and transwell to detect cell migration and invasion.ResultsThe RPL34 gene expression was up-regulated in OSCC tissues and cells. The RPL34 expression was significantly correlated with differentiation degree, TNM stage and lymph node metastasis. Patients with positive RPL34 expression had a poorer prognosis. After inhibition of RPL34 expression, the proliferation of SCC-4 cells was slowed down at 24h, 48h, 72h and 96h respectively, and both the migration distance and the number of invasive cells were reduced, while there was an increase in the ratio of cells at G0/G1 stage and cell apoptosis.ConclusionThe RPL34 gene was highly expressed in OSCC, while silencing RPL34 could block cell proliferation and metastasis, but promote cell apoptosis, suggesting the RPL34 gene to be a new promising clinical target for OSCC therapy.



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nab-Paclitaxel-based induction chemotherapy with or without cetuximab for locally advanced head and neck squamous cell carcinoma

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Publication date: September 2017
Source:Oral Oncology, Volume 72
Author(s): Douglas Adkins, Jessica Ley, Peter Oppelt, Tanya M. Wildes, Hiram A. Gay, Mackenzie Daly, Jason Rich, Randal C. Paniello, Ryan Jackson, Patrik Pipkorn, Brian Nussenbaum, Kathryn Trinkaus, Wade Thorstad
ObjectivesTo explore the effect of incorporating cetuximab into induction chemotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC).Materials and methodsRetrospective comparative analysis of two consecutive prospective phase II trials was performed: trial 1 with nab-paclitaxel/cisplatin/5-FU and cetuximab (APF-C; n=30) and trial 2 with APF (n=30). Patients were scheduled to receive chemoradiation therapy (CRT) with cisplatin. T2-4 classification oropharynx (OP)/larynx/hypopharynx SCC were included. Cumulative incidence of death of disease (CIDD), overall survival (OS), and cumulative incidence of relapse were compared between APF-C and APF.ResultsNo significant differences in patient or tumor characteristics were noted between the groups. Median follow-up of surviving patients was 52 (25–95) months. Relapse occurred in 5 (17%) patients treated with APF-C and in 2 (7%) treated with APF (p=0.37). In human papillomavirus (HPV)-related OPSCC (n=34), the CIDD at 52months was 3.4% with APF-C and 2.6% with APF and the two-year OSs were 94%. In HPV-unrelated HNSCC (n=25), the CIDD at 52months was 4.4% with APF-C and 3.3% with APF and two-year OSs were 83% and 92%, respectively. CIDD or OS did not differ when stratified by treatment group and HPV status (CIDD: p=0.80; OS: p=0.30).ConclusionThis exploratory retrospective comparative analysis demonstrated no significant difference in CIDD, OS, or cumulative incidence of relapse between patients treated with APF-C or APF.



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Parental Actionability of Educational Materials Regarding Laryngotracheal Reconstruction.

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Parental Actionability of Educational Materials Regarding Laryngotracheal Reconstruction.

JAMA Otolaryngol Head Neck Surg. 2017 Jul 06;:

Authors: Wong K, Keefe KR, Gilad A, Chong-Sun Li CJ, Levi JR

PMID: 28687835 [PubMed - as supplied by publisher]



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Addressing the Challenges in Tonsillectomy Research to Inform Health Care Policy: A Review.

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Addressing the Challenges in Tonsillectomy Research to Inform Health Care Policy: A Review.

JAMA Otolaryngol Head Neck Surg. 2017 Jul 06;:

Authors: Mandavia R, Schilder AGM, Dimitriadis PA, Mossialos E

Abstract
Importance: Eighty-five percent of investment in medical research has been wasted, with lack of effect on clinical practice and policy. There is increasing effort to improve the likelihood of research being used to influence clinical practice and policy. Tonsillectomy is one of the most common otorhinolaryngologic surgical procedures, and its frequency, cost, and morbidity create a clear need for evidence-based guidelines and policy. The first systematic review on tonsillectomy was conducted 40 years ago and highlighted the lack of definitive evidence for the procedure. Since that study, the body of evidence has still not been able to sufficiently inform policy. This review provides an overview of the key challenges in research to inform tonsillectomy policy and recommendations to help bridge the evidence-policy gap.
Observations: The challenges in using research to inform policy can be summarized as 4 main themes: (1) non-policy-focused evidence and lack of available evidence, (2) quality of evidence, (3) communication of research findings, and (4) coordinating time frames. Researchers and decision makers should be aware of the limitations of research designs and conflicts of interest that can undermine policy decisions. Researchers must work with decision makers and patients throughout the research process to identify areas of unmet need and political priority, align research and policy time frames, and disseminate research findings. Incentives for researchers should be reorganized to promote dissemination of findings.
Conclusions and Relevance: It is important to consider why evidence gaps in tonsillectomy research have not been addressed during the past 40 years despite considerable investment in time and resources. These findings and recommendations will help produce research that is more responsive to policy gaps and more likely to result in policy changes.

PMID: 28687832 [PubMed - as supplied by publisher]



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Addressing the Challenges for Otolaryngology Research to Inform Patient Care and Outcomes.

Related Articles

Addressing the Challenges for Otolaryngology Research to Inform Patient Care and Outcomes.

JAMA Otolaryngol Head Neck Surg. 2017 Jul 06;:

Authors: Piccirillo JF, Yueh B, Davies L, Weaver E

PMID: 28687818 [PubMed - as supplied by publisher]



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Etiologic and Audiologic Characteristics of Patients With Pediatric-Onset Unilateral and Asymmetric Sensorineural Hearing Loss.

Related Articles

Etiologic and Audiologic Characteristics of Patients With Pediatric-Onset Unilateral and Asymmetric Sensorineural Hearing Loss.

JAMA Otolaryngol Head Neck Surg. 2017 Jul 06;:

Authors: Lin PH, Hsu CJ, Lin YH, Lin YH, Lee HY, Wu CC, Liu TC

Abstract
Importance: Pediatric-onset unilateral and asymmetric sensorineural hearing loss (SNHL) is a common condition, but in most patients, the cause remains unclear; thus, determination of the hearing outlook is difficult.
Objective: To analyze the etiologic and audiologic characteristics of pediatric-onset unilateral and asymmetric SNHL.
Design, Setting, and Participants: In this retrospective cohort study performed from January 1, 2008, through December 31, 2016, patients at a tertiary referral center who were diagnosed with pediatric-onset unilateral or asymmetric SNHL were divided into 3 groups according to their hearing levels: unilateral hearing loss with scaled-out levels (UHL-SO), unilateral hearing loss with residual hearing (UHL-RH), and asymmetric hearing loss (AHL).
Main Outcomes and Measures: Basic demographic data, family and medical histories, audiologic results, imaging findings, and genetic results were ascertained and compared among patients of the 3 groups.
Results: A total of 133 patients (mean [SD] age, 9.1 [10.9] years; 63 [47.4%] male and 70 [52.6%] female), including 50 with UHL-SO, 42 with UHL-RH, and 41 with AHL, were enrolled for analyses. Of 50 patients with UHL-SO, 49 (98.0%) had stable hearing levels with time, whereas 10 of 42 patients with UHL-RH (23.8%) and 18 of 41 patients with AHL (43.9%) revealed progressive or fluctuating hearing loss. Inner ear malformations detected with temporal bone high-resolution computed tomography, particularly cochlear aperture stenosis, were detected at higher rates in patients with UHL-SO (9 of 31 [29.0%]) and UHL-RH (6 of 24 [25.0%]) than in those with AHL (1 of 30 [3.3%]). In contrast, screening for mutations in 3 common deafness genes-GJB2, SLC26A4, and MTRNR1-achieved definite diagnosis in a higher percentage of patients with AHL (10 of 37 [27.0%]) than patients with UHL-SO (0 of 33) and UHL-RH (1 of 25 [4.0%]).
Conclusions and Relevance: The UHL-SO and UHL-RH conditions share a common or similar etiopathogenesis different from that of AHL. Imaging studies and genetic testing might be prioritized during the respective general etiologic workups for patients with UHL and AHL. Regular hearing checkups are warranted for patients with UHL and AHL because a certain proportion of patients might sustain progression in SNHL.

PMID: 28687817 [PubMed - as supplied by publisher]



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IL-33 improves wound healing through enhanced M2 macrophage polarization in diabetic mice

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Publication date: October 2017
Source:Molecular Immunology, Volume 90
Author(s): Rongguo He, Hui Yin, Baohong Yuan, Tao Liu, Li Luo, Ping Huang, Liangcheng Dai, Kang Zeng
IL-33 is a newly discovered member of the IL-1 family and has been identified as a potent inducer of Th2 type immunity. Emerging evidence imply that IL-33 may also act as an alarm to alert the immune system when released by epithelial barrier tissues during trauma or infection. In this study, we further investigate the potential efficacy of IL-33 on dermal wound healing in streptozotocin–induced diabetic mice. A full-thickness skin wound was generated on the back of diabetic mice and treated with IL-33 or vehicle topically. Our data showed that IL-33 delivery contributed to diabetic wound closure with wounds gaping narrower and exhibiting elevated re-epithelialization. IL-33 promoted the new extracellular matrix (ECM) deposition and angiogenesis formation, which indicates an important role of IL-33 on matrix synthesis and neovascularization. Meanwhile, IL-33 accelerated the development of M2 macrophages in wound sites in vivo, and amplified IL-13-induced polarization of bone marrow-derived macrophages toward a M2 phenotype in vitro. Furthermore, IL-33-amplified M2 macrophages augmented the proliferation of fibroblasts and ECM deposition. All together, these results strongly suggest manipulation of IL-33-mediated signal might be a potential therapeutic approach for diabetic skin wounds.



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The effect of saliva on the fate of nanoparticles

Abstract

Objectives

The design of nanocarriers for local drug administration to the lining mucosa requires a sound knowledge of how nanoparticles (NPs) interact with saliva. This contact determines whether NPs agglomerate and become immobile due to size- and interaction-filtering effects or adsorb on the cell surface and are internalized by epithelial cells. The aim of this study was to examine the behavior of NPs in saliva considering physicochemical NP properties.

Materials and methods

The salivary pore–size distribution was determined, and the viscosity of the fluid inside of the pores was studied with optical tweezers. Distinct functionalized NPs (20 and 200 nm) were dispersed in saliva and salivary buffers and characterized, and surface-bound MUC5B and MUC7 were analyzed by 1D electrophoresis and immunoblotting. NP mobility was recorded, and cellular uptake studies were performed with TR146 cells.

Results

The mode diameter of the salivary mesh pores is 0.7 μm with a peak width of 1.9 μm, and pores are filled with a low-viscosity fluid. The physicochemical properties of the NPs affected the colloidal stability and mobility: compared with non-functionalized particles, which did not agglomerate and showed a cellular uptake rate of 2.8%, functionalized particles were immobilized, which was correlated with agglomeration and increased binding to mucins.

Conclusion

The present study showed that the salivary microstructure facilitates NP adsorption. However, NP size and surface functionalization determine the colloidal stability and cellular interactions.

Clinical relevance

The sound knowledge of NP interactions with saliva enables the improvement of current treatment strategies for inflammatory oral diseases.



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