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Πέμπτη 11 Φεβρουαρίου 2021

Knockdown of KIF15 promotes cell apoptosis by activating crosstalk of multiple pathways in ovarian cancer: bioinformatic and experimental analysis.

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Knockdown of KIF15 promotes cell apoptosis by activating crosstalk of multiple pathways in ovarian cancer: bioinformatic and experimental analysis.

Int J Clin Exp Pathol. 2021;14(2):267-291

Authors: Sun X, Chen M, Liao B, Liang Z

Abstract
BACKGROUND: Ovarian cancer (OC) is the most lethal malignancy of women. Unlimited proliferation is a fundamental feature of OC cells. The genes associated with cell proliferation may be histopathologic biomarkers and targets of anti-tumor therapeutic strategies. The present study aimed to identify proliferation-associated biomarkers with prognostic, diagnostic, and therapeutic value and reveal the underlying molecular mechanism of candidate genes involved in OC by a combination of bioinformatic and experimental methods.
RESULTS: KIF15 was upregulated in early-stage OC tissues and could predict poor prognosis of patients of Stage I and II. The knockdown of KIF15 significantly inhibited cell proliferation, tumor formation, and growth as well as promoting apoptosis of OC cells. A combination of experimental and bioinformatic analyses revealed KIF15 knockdown promoted cell apoptosis by activating crosstalk of multiple pathways in OC.
CONCLUSION: KIF15, an early-stage prognostic gene, was identified as a candidate histopathologic biomarker and therapeutic target of OC.

PMID: 33564360 [PubMed]

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Key regulatory genes and signaling pathways involved in islet culture: a bioinformatic analysis.

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Key regulatory genes and signaling pathways involved in islet culture: a bioinformatic analysis.

Int J Clin Exp Pathol. 2021;14(2):292-303

Authors: Shi J, Zhang YQ, Hao DD, Fu SH, Meng JL

Abstract
Type 1 diabetes (T1D) is characterized by non-ideal mass and low survival rate of islets. Therefore, it is necessary to find intrinsic factors that prolong the survival of islets. This study aimed to track out hub genes and pathways in the process of islet culture by bioinformatic analysis. We downloaded the gene expression microarray of GSE42591 from the Gene Expression Omnibus (GEO). Aberrant Differentially methylated genes (DMGs) were obtained using the GEO2R tool. Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analyses were performed on selected genes by using the Database for Annotation Visualization and Integrated Discovery (DAVID). A protein-protein interaction (PPI) network was constructed with the Retrieval of Interacting Genes (STRING) and visualized in Cytoscape 3.7.2. A total of 434 genes were overexpressed and 114 genes underexpressed in fresh to cultured 4 h tissue. KEGG pathway enrichment analyses revealed the TG F-beta signaling pathway, MAPK signaling pathway, or VEGF signaling pathway. The genes FN1, MKI67, IGF1, MAPK14, COL1A1 might be involved in islet culture. In general, this work scrutinized islet culture-relevant knowledge and provided insight into the regulation and mediation of islet survival.

PMID: 33564361 [PubMed]

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Use of Vascular Clues to Locate Ectopic Parathyroid Glands and Predict Anatomic Abnormalities

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This case report describes a woman in her 60s who was referred for primary hyperparathyroidism and was subsequently diagnosed with an aberrant right subclavian artery.
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Nasal Saline Irrigations in the COVID-19 Pandemic—Reply

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In Reply We thank Radulesco et al for their interest in our article and their letter in response. We agree that it would be beneficial to explore the utility of other topical additives in prevention and treatment of respiratory viruses, such as severe acute respiratory syndrome coronavirus 2. Regarding the potential use of copper, it is certainly encouraging to note its antiviral efficacy. The literature is particularly supportive of its use as an antimicrobial coating for surfaces. However, there is not yet strong evidence regarding the safety of copper as an additive for nasal saline irrigations. As the authors address, 1 preliminary study performed by Huang et al does note the safety of a nasal solution enriched with copper, among other additives. However, the product evaluated in that study reports only that it is enriched with coppe r and does not further specify the concentration or form of copper used. Though the aforementioned study notes safety of a nasal solution enriched with copper, animal studies of nasally applied copper salts and nanoparticles have demonstrated the potential toxic effects of copper, resulting in direct olfactory neuron damage or intracranial translocation, resulting in neurologic damage. These concerns were further described in a recent review of copper toxicology, which notes concern for copper-induced cell damage through the release of reactive oxygen species.
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Increasing Confidence in Detecting Metastatic Thyroid Cancer With Neck Ultrasonography

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Ultrasonography is the modality of choice for neck nodal surveillance after thyroidectomy for patients with differentiated thyroid cancer (DTC), according to the American Thyroid Association and the European Thyroid Association. In a cross-sectional survey study published in this issue of JAMA Otolaryngology–Head & Neck Surgery, Kovatch and colleagues draw attention to low confidence in ultrasonography among a cohort of 320 endocrinologists, general surgeons, and otolaryngologists. The authors found that only 1 in 5 physicians reported having high confidence in their own ability to use ultrasonography to detect lymph nodes suggestive of recurrence; 3 in 5 reported having high confidence in a radiologist's ability to detect recurrence; and 1 in 3 did not have high confidence in either their own or a radiologist's ability to detect recurrence.
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Transient Delivery of a KCNQ2/3-Specific Channel Activator 1 Week After Noise Trauma Mitigates Noise-Induced Tinnitus

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Abstract

Exposure to loud noise can cause hearing loss and tinnitus in mice and humans. In mice, one major underlying mechanism of noise-induced tinnitus is hyperactivity of auditory brainstem neurons, due at least in part, to decreased Kv7.2/3 (KCNQ2/3) potassium channel activity. In our previous studies, we used a reflex-based mouse model of tinnitus and showed that administration of a non-specific KCNQ channel activator, immediately after noise trauma, prevented the development of noise-induced tinnitus, assessed 1 week after trauma. Subsequently, we developed RL-81, a very potent and highly specific activator of KCNQ2/3 channels. Here, to test the timing window within which RL-81 prevents tinnitus in mice, we modified and employed an operant animal model of tinnitus, where mice are trained to move in response to sound but not move in silence. Mice with behavioral evidence of tinnitus are expected to move in silence. We validated this mouse model by testing the ef fect of salicylate, which is known to induce tinnitus. We found that transient administration of RL-81 1 week after noise exposure did not affect hearing loss but reduced significantly the percentage of mice with behavioral evidence of tinnitus, assessed 2 weeks after noise exposure. Our results indicate that RL-81 is a promising drug candidate for further development for the treatment of noise-induced tinnitus.

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The Test of Masticating and Swallowing Solids (TOMASS): Reliability, Validity and Normative Data for the Adult Indian Population

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Abstract

The Test of Masticating and Swallowing Solids (TOMASS) is a reliable and well-validated tool to assess the effectiveness of solid bolus ingestion. Previous studies have established normative values for 4 to 80+ years across a range of commercially available crackers and countries. The current study aimed to establish normative data for the TOMASS across age and gender groups for a commercially available biscuit (cracker) for the adult Indian population. A total of 300 typical individuals in the age range of 21 to 80 years grouped by age and sex participated in the study. Participants were instructed to eat a commercially (locally) available biscuit 'as quickly and comfortably as possible,' and the task was video recorded. The recorded video samples were analyzed to obtain measures of the number of bites, number of masticatory cycles, number of swallows, and total time taken to complete the ingestion of biscuit. Cronbach's α values revealed a moderat e to good (0.71 to 0.82) test–retest reliability; ICC values were suggestive of a high level (> 0.76) of interrater reliability for all the measures of TOMASS. The results of the one-way ANOVA revealed a significant main effect of age (F = 3.12, p < 0.01) and gender (F = 4.37, p < 0.01), but not an interaction between the two. Normative data stratified by age and gender were also generated. The TOMASS assessment procedure was feasible, reliable, and valid. In the current study, we observed that males took fewer bites, took less time, chewed less, and swallowed fewer times than females. A definitive age effect was observed for the number of bites, masticatory cycles, and total time. The normative data generated by the current study can serve as clinical benchmarks to assess the ingestion of solid bouls in the adult Indian population.

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Concept and Prelimnary Design of an Economical Bag Valve Mask Compressor as a Prototype for Simple Ventilator During COVID-19

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Abstract

The pandemic of COVID 19 has taken a massive toll of lives since its outbreak. Throughout the world with a large number of people being affected by covid 19, the need for the ventilators has risen. However, there is disproportionate ratio of demand versus supply of ventilators due to the menace caused by Covid 19 which has become unmanageable. This paper describes the design of the low cost portable mechanical bag valve mask compressor which could serve as a preliminary ventilator for the patients needing ventilator support in COVID 19. This prototype ventilator delivers breaths by compressing a conventional bag-valve mask (BVM) with a motor, eliminating the need for a human operator for the BVM. It is driven by a wind shield wiper electric motor powered by a 12 V battery. Additionally it can be used to deliver oxygen through either Laryngeal mask or compact face masks or nasopharyngeal airways where intubation is awaited in early breathlessness. Future additions for our prototype ventilator will include a controllable inspiration to expiration time ratio, a pressure relief valve, PEEP capabilities and an LCD screen. With a prototyping cost of only $150, the concept of BVM compressor is a low-cost, low-power portable ventilator technology that will provide essential ventilator features at a fraction of the cost of existing technology.

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The Role of Systemic Therapy in Advanced Cutaneous Squamous Cell Carcinoma

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Systemic therapy for patients with head and neck cutaneous squamous cell carcinoma (HNCSCC) generally is used for patients with advanced disease and most often employed for patients in the palliative setting when disease is unresectable and/or widely metastatic. Cytotoxic agents and epidermal growth factor receptor pathway targeted therapy have been utilized most commonly, with few clinical data to support their efficacy. Adjuvant postoperative chemoradiation with platinum has been called into question based on recent data. Programmed cell death protein 1 receptor immune checkpoint inhibitors have demonstrated profound activity in HNCSCC, and cemiplimab and pembrolizumab now are approved for use for unresectable/metastatic disease.
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Posture, Gait, Quality of Life, and Hearing with a Vestibular Implant

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Approximately 1.8 million adults worldwide have severe bilateral vestibular hypofunction that results in chronic disequilibrium, oscillopsia, postural instability, and unsteady gait owing to failure of vestibular reflexes that stabilize the eyes, head, and body. Because affected persons must devote…
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Primary Orbital Melanoma: An Investigation of a Rare Malignancy Using the National Cancer Database

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Objectives

Primary orbital melanoma (POM) is a rare disease with limited data on survival and best treatment practices. Here we utilize the National Cancer Database (NCDB) to determine the overall survival (OS) and covariates that influence mortality.

Study Design: Retrospective cohort study.

Methods

All patients diagnosed with POM from 2004 to 2016 were identified in the NCDB. Patient and oncologic data were analyzed using the Kaplan–Meier method and multivariate models for the primary outcome of OS.

Results

A total of 129 patients were identified. Median OS was 36.9 months (95% confidence interval [CI] 24.1–78.7 months) with mean 5‐year survival of 42.0% (CI 33.2%–53.2%). Treatments received included surgery alone (43.4%), radiation alone (23.3%), and surgery followed by radiation (20.2%). The multivariate model demonstrated an increased risk of death associated with age over 80 years (hazard ratio [HR] 3.41, CI 1.31–8.86, P = .012), a Charlson‐Deyo comorbidity score of 2 or greater (HR 5.30, CI 1.87–15.03, P = .002), and no treatment (HR 2.28, CI 1.03–5.06, P = .042). For every 1 cm increase in tumor size, there was an increased risk of death (HR 1.06, CI 1.00–1.13, P = .039). When compared to surgery alone, no other treatment modality had an effect on OS.

Conclusions

This study leveraged multiyear data from the NCDB to provide prognostic and demographic information on the largest known cohort of POM cases. Increased age, increased comorbidities, not receiving treatment, and larger tumor size were associated with increased mortality. There was no clear survival advantage for specific treatments.

Level of Evidence

IV Laryngoscope, 2021

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Complications of Free Flaps for Oromandibular Reconstruction

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Objectives/Hypothesis

To determine the frequency and management of short‐ and long‐term complications related to oromandibular free flap reconstruction and identify potentially predictive factors of hardware complications.

Study Design

Retrospective chart review.

Methods

A retrospective database from chart review was formed consisting of 266 oromandibular free flap reconstructions performed at a single institution over a 15‐year period. Data were collected on demographics, surgical treatment, complications, and management of complications. Subgroup univariate and multivariate analyses were performed to compare patients with hardware complications and those without.

Results

Eighty‐one of 266 patients (30.5%) that underwent oromandibular reconstruction had an early complication (<4 weeks after surgery), and the most common complications were cervical wound dehiscence (11.3%) and fistulas (9.40%). Eighty of 266 patients (30.1%) had a long‐term complication (>4 weeks after surgery) and the most common complication was plate exposure (26.7%). Univariate and multivariate analyses showed no association between whether there was hardware extrusion and fibula versus scapula, smoking history, virtual surgical planning (VSP), and dental implantation (P > .05). Only early complications (OR, 3.59, 95% CI, 1.83–7.05, P < .01) and patients undergoing oromandibular reconstruction for osteoradionecrosis (OR, 2.26, 95% CI, 1.10–4.64, P = .03) were strongly and independently associated with subsequent hardware extrusion on univariate analysis.

Conclusions

Both short‐ and long‐term complications are common after oromandibular reconstruction. The most important predictive factor for a late complication is an early complication and prior radiation. There was no difference of plate complications among the various free flap types. Dental implantation and use of VSP were not associated with hardware complications.

Level of Evidence

4 Laryngoscope, 2021

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