Tuesday, August 10, 2021

Presentation and management of post-operative cerebrospinal fluid leaks after sphenoclival expanded endonasal surgery: A single institution experience

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J Clin Neurosci. 2021 Sep;91:13-19. doi: 10.1016/j.jocn.2021.06.036. Epub 2021 Jun 27.

ABSTRACT

While surgical approaches and techniques of expanded endonasal approach (EEA) surgery have been well described, little data exist regarding management of post-operative cerebrospinal fluid (CSF) leaks. In this study, we examined a surgeon's continuous 12-year experience with failed closure of sphenoclival skull base defects. We conducted a retrospective case series of patients identified with post-operative CSF leaks after EEA of the sphenoclival axis, managed by a single otolaryngologist at a minimally invasive skull base center. Ten out of 326 patients required therapeutic intervention for central skull base defect closure failure. Median time to presentation of CSF leak was 25 days (range 6-542 days). Symptoms included rhinorrhea (n = 7), meningitis (n = 6), and pneumocephalus (n = 1). The majority of patients (7 of 10) were first managed by lum bar drain placement - one of which had resolution of his/her CSF leak. Overall, 9 of 10 patients required endoscopic repair. The majority of the post-operative CSF leaks (9/13, 69.2%) were repaired using a vascularized mucosal flap. There were 3 patients who required a second revision surgery. All CSF leaks were repaired without completely deconstructing the initial repair. Failure sites most frequently occurred outside of the sella (80%), likely reflecting their direct relationship to the intracranial cisterns. Initial operative repair provided definitive treatment in most cases (70%). Correct placement of a vascularized local pedicle-based flap is essential for successful repair. Knowledge of alternative flaps is particularly important when the nasoseptal flap is no longer available.

PMID:34373017 | DOI:10.1016/j.jocn.2021.06.036

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Course of Hyposmia and Hypogeusia and their Relationship with Severity of COVID-19 Disease among Indian Population

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Abstract

Aims: Hyposmia and hypogeusia are one of the symptoms of COVID-19. Occurrence and course of these symptoms and their relationship with severity of COVID-19 disease are studied. Materials and Methods: This was a prospective cohort study, including consenting adult SARS CoV-2 positive patients of both genders, admitted to a Covid Hospital in Puducherry, India. This questionnaire- based study was conducted for a period 4 months from 1st October 2020 to 31st January 2021, and collected data was analyzed using SPSS version 24.0 software. Results: Out of 639 participants, 412 (64.5%) were males, 227 (35.5%) were females. Total cases of new onset hyposmia were 167 (26.1%), and total patients with new onset hypogeusia were 172 (26.91%). 216 (33.80%) had either hyposmia/hypogeusia. First symptom as hyposmia was noted in 49 (7.67%) patients, and as hypogeusia in 20 (3.13%) patients before development of any other symptoms. 216 (33.80%) patients had either smell or taste di sturbance as one of their symptoms. By the end of 5 weeks of illness, 96.41% of hyposmic patients, and 97.67% of hypogeusic patients recovered fully. There was no statistically significant difference between presence or absence of hyposmia/hypogeusia and severity of COVID-19 disease (p value = 0.95). Conclusion: The occurrence of hyposmia and hypogeusia among Indian COVID-19 patients is more than 26%. Presence or absence of hyposmia/hypogeusia is not a predictor of severity of COVID-19 disease. More than 96% of the patients fully recovered their sense of smell and taste sensation by the end of 5 weeks.

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Effects of a conservative in-patient voice treatment on the voice-related self-concept

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Eur Arch Otorhinolaryngol. 2021 Aug 10. doi: 10.1007/s00405-021-07021-y. Online ahead of print.

ABSTRACT

PURPOSE: Observational study to determine if the voice-related self-concept as measured via the Fragebogen zur Erfassung des Stimmlichen Selbstkonzepts FESS (questionnaire for the assessment of the voice self-concept) can be improved through in-patient voice therapy.

METHODS: 234 female and 80 male patients that underwent an intensive 3- to 4-week in-patient voice treatment due to varying types of dysphonia. After imputation of missing items but not missing questionnaires, 255 patients were eligible for FESS evaluation, 313 for VHI-12 evaluation. The German questionnaire for the assessment of the voice self-concept (FESS) and the German 12-item short-form of the Voice Handicap Index (VHI-12) were administered at the beginning and at the end of the hospital stay. Before-after comparisons are made visually and via t test.

RESULTS: The Voice Handicap was significantly reduced, demonstrating the effectiveness of the administered therapy. Of the three scales of the FESS, the relationship with one's own voice and the awareness of the use of one's own voice was increased and thus improved. The connection between voice and emotional changes decreased significantly but only slightly.

CONCLUSION: Conservative voice rehabilitation can not only reduce the voice handicap, but also improve the voice self-concept and the results can be measured.

PMID:34374843 | DOI:10.1007/s00405-021-07021-y

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E-Cigarette Vaping-Related Vocal Fold Injury: A Case Report

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Vaping products, also known as e-cigarettes, are battery-operated devices, which heat a solution into an aerosol (vapor) that is inhaled. These products have been present in the U.S. for more than a decade1 and may help patients to reduce or stop tobacco consumption. Although worldwide use is increasing, many questions remain about the impact of vaping on the vocal folds. In this letter, we report the history of a female who developed vaping-related vocal fold injury.
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Artificial intelligence in otorhinolaryngology

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HNO. 2021 Aug 10. doi: 10.1007/s00106-021-01095-0. Online ahead of print.

ABSTRACT

BACKGROUND: The continued advancement of digitalization increasingly allows deployment of artificial intelligence (AI) algorithms, leveraging profound effects on society and medicine.

OBJECTIVE: This article aims to provide an overview of current developments and futures perspectives of AI in otorhinolaryngology.

MATERIALS AND METHODS: Scientific studies and expert analyses were ev aluated and discussed.

RESULTS: AI can increase the value of current diagnostic tools in otorhinolaryngology and enhance surgical precision in head and neck surgery.

CONCLUSION: AI has the potential to further improve diagnostic and therapeutic procedures in otorhinolaryngology. This technology, however, is associated with challenges, for example in the domain of privacy and data security.

PMID:34374811 | DOI:10.1007/s00106-021-01095-0

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MicroRNA-449a inhibits cell proliferation and migration by regulating mutant p53 in MDA-MB-468 cells

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Exp Ther Med. 2021 Sep;22(3):1020. doi: 10.3892/etm.2021.10452. Epub 2021 Jul 15.

ABSTRACT

The present study aimed to investigate the role of microRNA (miR)-449a in the proliferation, migration and apoptosis of MDA-MB-468 breast cancer cells and examine the association between miR-449a and mutant p53 in these cells. Cell proliferation, migration and invasion were examined using a crystal violet staining assay, wound healing scratch assay and Transwell assay, respectively. The expression level of miR-449a and p53 was detected by reverse transcription-quantitative PCR or western blotting. The results indicated that knockdown of mutant p53 suppressed the proliferation and migration of MDA-MB-468 cells by inhibiting the PI3K/AKT/mTOR signaling pathway. In addition, miR-449a suppressed proliferation and migration via downregulation of mutant p53 expression in MDA-MB-468 cells. Therefore, miR-449a may function as a tumor suppressor by regula ting p53 expression in breast cancer cells, which may have potential implications in the treatment of patients with triple-negative breast cancer carrying mutant p53.

PMID:34373706 | PMC:PMC8343910 | DOI:10.3892/etm.2021.10452

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iTRAQ-based quantitative proteomics analysis of the hepatoprotective effect of melatonin on ANIT-induced cholestasis in rats

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Exp Ther Med. 2021 Sep;22(3):1014. doi: 10.3892/etm.2021.10446. Epub 2021 Jul 15.

ABSTRACT

The therapeutic effects of melatonin on cholestatic liver injury have received widespread attention recently. The aim of the present study was to investigate the mechanisms of the anti-cholestatic effects of melatonin against α-naphthyl isothiocyanate (ANIT)-induced liver injury in rats and to screen for potential biomarkers of cholestasis through isobaric tags for relative and absolute quantitation (iTRAQ) proteomics. Rats orally received melatonin (100 mg/kg body weight) or an equivalent volume of 0.25% carboxymethyl cellulose sodium salt 12 h after intraperitoneal injection of ANIT (75 mg/kg) and were subsequently sacrificed at 36 h after injection. Liver biochemical indices were determined and liver tissue samples were stained using hematoxylin-eosin staining, followed by iTRAQ quantitative proteomics to identify potential underlying therape utic mechanisms and biomarkers. The results suggested that the expression levels of alanine transaminase, aspartate aminotransferase, total bilirubin and direct bilirubin were reduced in the rats treated with melatonin. Histopathological observation indicated that melatonin was effective in the treatment of ANIT-induced cholestasis. iTRAQ proteomics results suggested that melatonin-mediated reduction in ANIT-induced cholestasis may be associated with enhanced antioxidant function and relieving abnormal fatty acid metabolism. According to pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes, the major metabolic pathways for the metabolism of melatonin are fatty acid degradation, the peroxisome proliferator-activated receptor signaling pathway, fatty acid metabolism, chemical carcinogenesis, carbon metabolism, pyruvate metabolism, fatty acid biosynthesis and retinol metabolism, as well as drug metabolism via cytochrome P450. Malate dehydrogenase 1 and glutathi one S-transferase Yb-3 may serve as potential targets in the treatment of ANIT-induced cholestasis with melatonin.

PMID:34373700 | PMC:PMC8343461 | DOI:10.3892/etm.2021.10446

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Molecular diagnosis of McArdle disease using whole-exome sequencing

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Exp Ther Med. 2021 Sep;22(3):1029. doi: 10.3892/etm.2021.10461. Epub 2021 Jul 18.

ABSTRACT

Whole-exome sequencing (WES) analysis has been used recently as a diagnostic tool for finding molecular defects. In the present study, researchers attempted to analyze molecular defects through WES in a 13-year-old female patient who had not been diagnosed through a conventional genetic approach. DNA was extracted and subjected to WES analysis to identify the genetic defect. A total of 106,728 exons and splicing variants were selected, and synonymous single nucleotide variants (SNVs) and general single nucleotide polymorphisms (SNPs) were filtered out. Finally, nonsynonymous SNVs (c.C415T and c.C389T) of the PYGM gene were identified in nine compound heterozygous mutations. PYGM encodes myophosphorylase and degrades glycogen in the muscle to supply energy to muscle cells. The present study revealed that the patient's father had a c. C389T mutation and the mother had a c.C415T mutation, resulting in A130V and R139W missense mutations, respectively. To the best of our knowledge, the A130V variant in PYGM has not been reported in the common variant databases. All variations of the patient's family detected using WES were verified by Sanger sequencing. Because the patient had compound heterozygous mutations in the PYGM gene, the patient was presumed to exhibit markedly decreased muscle phosphorylase activity. To assess the function of myophosphorylase, an ischemic forearm exercise test was performed. The blood ammonia level sharply increased and the lactate level maintained a flat curve shape similar to the typical pattern of McArdle disease. Therefore, the diagnosis of the patient was confirmed to be McArdle disease, a glycogen storage disease. Through WES analysis, accurate and early diagnosis could be made in the present study. This report describes a novel compound heterozygous mutation of the PYGM gene in a Korean patient.

PMID:34373715 | PMC:PMC8343624 | DOI:10.3892/etm.2021.10461

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Morphine pretreatment protects against cerebral ischemic injury via a cPKCγ-mediated anti-apoptosis pathway

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Exp Ther Med. 2021 Sep;22(3):1016. doi: 10.3892/etm.2021.10448. Epub 2021 Jul 15.

ABSTRACT

It has been reported that morphine pretreatment (MP) can exert neuroprotective effects, and that protein kinase C (PKC) participates in the initiation and development of ischemic/hypoxic preconditioning in the brain. However, it remains unknown whether PKC is involved in MP-induced neuroprotection. The aim of the present study, which included in vivo and in vitro experiments, was to determine whether the conventional γ isoform of PKC (cPKCγ) was involved in the protective effects of MP against cerebral ischemic injury. The present study included an in vivo experiment using a mouse model of middle cerebral artery occlusion and an in vitro experiment using neuroblastoma N2a cells with oxygen-glucose deprivation (OGD). Furthermore, a cPKCγ antagonist, Go6983, was used to determine the involvement of cPKCγ in the prote ctive effects of MP against cerebral ischemic injury. In the in vivo experiment, neurological deficits, ischemic infarct volume, neural cell damage, apoptosis and caspase-3 activation were evaluated. In the in vitro experiment, flow cytometry was used to determine the activation of caspase-3 in N2a cells with OGD. It was found that MP protected against cerebral ischemic injury. However, intracerebroventricular injection of the cPKCγ antagonist before MP attenuated the neuroprotective effect of MP and increased the activation of cleaved caspase-3. These findings suggested that MP may provide protection against cerebral ischemic injury via a cPKCγ-mediated anti-apoptosis pathway.

PMID:34373702 | PMC:PMC8343874 | DOI:10.3892/etm.2021.10448

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Weighted gene co-expression network analysis of the association between upregulated AMD1, EN1 and VGLL1 and the progression and poor prognosis of breast cancer

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Exp Ther Med. 2021 Sep;22(3):1030. doi: 10.3892/etm.2021.10462. Epub 2021 Jul 18.

ABSTRACT

Breast cancer is the most prevalent malignancy among females, but the molecular mechanisms involved in its pathogenesis and progression have remained to be fully elucidated. The aim of the present study was to identify novel potential therapeutic targets for breast cancer. The dataset GSE76275 was downloaded from the Gene Expression Omnibus database and weighted gene co-expression network analysis (WGCNA) was performed to identify hub genes. Furthermore, the dataset GSE25055, containing gene expression data and clinical information, was downloaded to validate the expression and survival association of these hub genes. In addition, the datasets GSE25065 and GSE42568 were used to validate the association between hub gene expression levels and clinical features. Immunohistochemistry (IHC), reverse transcription-quantitative PCR, as well as prolifera tion, migration, invasion and apoptosis assays, were used to verify gene expression and function. A total of 4,052 genes were selected for WGCNA and 18 modules were established; the red module was identified as the key module, as it had a strong positive correlation with the tumor grade. Survival analyses of hub genes [S-adenosylmethionine decarboxylase proenzyme (AMD1), homeobox protein engrailed-1 (EN1) and vestigial-like protein (VGLL1)] indicated that higher levels of gene expression were associated with poor prognosis of patients with breast cancer. This association was based on survival analysis of GSE25055 using the Kaplan-Meier plotter tool. Expression validation revealed that the upregulation of hub genes was associated with advanced tumor grade and malignant molecular subtype (basal-like). IHC results from the Human Protein Atlas also demonstrated that protein expression levels of the hub genes were higher in tumor tissues compared with those in adjacent normal tissues. Fu rthermore, the expression levels of AMD1, EN1 and VGLL1 were strongly correlated with each other. These results demonstrated that AMD1 is highly expressed in breast cancer tissues and cells and AMD1 knockdown decreased the proliferation and metastatic potential, while increasing apoptosis of breast cancer cells. These results suggested that AMD1, EN1 and VGLL1 are likely to contribute to breast cancer progression and unfavorable prognosis.

PMID:34373716 | PMC:PMC8343771 | DOI:10.3892/etm.2021.10462

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Comparison of the differentiation abilities of bone marrow-derived mesenchymal stem cells and adipose-derived mesenchymal stem cells toward nucleus pulposus-like cells in three-dimensional culture

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Exp Ther Med. 2021 Sep;22(3):1018. doi: 10.3892/etm.2021.10450. Epub 2021 Jul 15.

ABSTRACT

Nucleus pulposus cell (NPC) transplantation can be a potential therapeutic approach for intervertebral disc degeneration (IDD). However, low cell viability has restricted the therapeutic capacity of NPCs, and sources of natural NPCs are limited. Bone marrow-derived mesenchymal stem cells (BMSCs) and adipose-derived mesenchymal stem cells (ADSCs) can be differentiated toward NPC-like cells. However, it is unknown whether there are differences in the abilities of these two cell types to differentiate into NPC-like cells, or which cell type exhibits the best differentiation ability. The present study compared the abilities of BMSCs and ADSCs to differentiate toward NPC-like cells with or without a 3D culture system to lay a foundation for stem cell transplantation therapy for IDD. BMSCs were isolated from the rat whole bone marrow cell using the rep eated adherent culture method. ADSCs were isolated from rat adipose tissues in the subcutaneous inguinal region using the enzyme digestion method. Cells were identified using flow cytometry. Cell viability was assessed via Cell Counting Kit-8 assays, and reverse transcription-quantitative PCR and western blotting were carried out to evaluate the expression of NPC markers and chondrocyte-specific genes. Glycosaminoglycans (GAGs) and proteoglycans were examined via Alcian blue and safranin O staining, respectively. ADSCs in 3D culture displayed the highest cell proliferative ability, compared with the 2D culture system and BMSC culture. In addition, ADSCs in 3D culture exhibited increased GAG and proteoglycan synthesis than BMSCs. Compared with BMSCs in 3D culture, ADSCs in 3D culture exhibited higher mRNA and protein expression of NPC marker genes (hypoxia-inducible factor 1-α, glucose transporter 1) and chondrocyte-specific genes (Sox-9, aggrecan and type II collagen). The present findings indicated that ADSCs exhibited a better ability to differentiate into NPC-like cells in 3D culture compared with BMSCs, which may be of value for the regeneration of intervertebral discs using cell transplantation therapy.

PMID:34373704 | PMC:PMC8343765 | DOI:10.3892/etm.2021.10450

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