Κυριακή 12 Δεκεμβρίου 2021

Upregulation of TLR9 may contribute to activation of microglia and painful diabetic neuropathy via the p38 MAPK pathway in rats

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Histol Histopathol. 2021 Dec 10:18405. doi: 10.14670/HH-18-405. Online ahead of print.

ABSTRACT

Painful diabetic neuropathy is a common chronic complication of diabetes, and the underlying mechanism remains largely elusive. A rat model of painful diabetic neuropathy was established via streptozotocin (STZ) injection and assessed as increased heat and mechanical hypersensitivity. An upregulation of TLR9 was observed in the spinal cords of rats injected with STZ and rat microglia (primary microglia and immortalized microglia HAPI) treated with high glucose. To investigate the role of TLR9 in high glucose-induced microglia activation, short hairpin RNAs targeting TLR9 were used in vitro to knock down TLR9 in HAPI cells. TLR9 interference suppressed the high glucose-induced expression and secretion of inflammatory cytokines (TNF-α, IL-1β, and IL-6), IBA-1 expression and the chemotaxis of HAPI microglia. Similar results were obtained when HAPI microglia were incubated with a p38 inhibitor (SB203580). P38 and ERK were downstream of TLR9 because TLR9 ablation markedly inhibited the phosphorylation of p38 and ERK. TLR9 was also knocked down in vivo via the injection of shTLR9 lentiviral vector into the rat spinal cord. Relief of STZ-induced heat and mechanical hypersensitivity was observed in rats with TLR9 interference, and TLR9 knockdown prevented STZ-induced inflammatory cytokine secretion and microglial and MAPK signaling activation. Our study revealed the participation of TLR9 in microglial activation and diabetes-induced hyperalgesia likely via the MAPK pathway. The targeting of TLR9 may be an effective strategy for the treatment of painful diabetic neuropathy.

PMID:34889455 | DOI:10.14670/HH-18-405

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Voice Performance Chart: A Pedagogical Tool to Enhance Vocal Expressive Ability in Acting Students

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The purpose of the present study was to explore the effectiveness of the Voice Performance Chart (VPCH) as a pedagogical training tool to enhance vocal expressive ability of 1st year acting students. Forty recorded audio samples were perceptually assessed by six blinded raters, using a five-points Likert scale for each of the dependent variables observed. Results showed that loudness, pitch, and speech rate variations significantly differ when comparing the vocal condition before and after a 11 weeks training period.
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Delayed vocal fold palsy caused by an undetected fish bone impacted in the tracheoesophageal groove

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Braz J Otorhinolaryngol. 2021 Nov 15:S1808-8694(21)00189-0. doi: 10.1016/j.bjorl.2021.04.013. Online ahead of print.

NO ABSTRACT

PMID:34893460 | DOI:10.1016/j.bjorl.2021.04.013

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EFFECT OF BRAFV600E AND TERT PROMOTER MUTATIONS ON THYROGLOBULIN RESPONSE IN DISTANT-METASTATIC DIFFERENTIATED THYROID CANCER

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Endocr Pract. 2021 Dec 7:S1530-891X(21)01410-5. doi: 10.1016/j.eprac.2021.12.005. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the impact of BRAFV600E and telomerase reverse transcriptase (TERT) promoter mutations in distant-metastatic differentiated thyroid cancer (DM-DTC) patients based on thyroglobulin (Tg) response to radioactive iodine (RAI) therapy.

METHODS: BRAFV600E and TERT mutations in primary tumors or metastatic lymph nodes of 114 DM-D TC patients were retrospectively examined. RAI avidity was evaluated based on posttreatment 131I-WBS. Tg response was dynamically assessed with a median follow-up of 56.50 months (interquartile range, 28.43-97.98 months).

RESULTS: BRAFV600E was detected in 38.6% of cases and TERT mutation in 21.1% of cases, and both BRAFV600E and TERT mutations were observed in 14.9% of cases. Patients with both mutations tended to be older at diagnosis (P<0.001), less multifocal (P=0.011) and have more aggressive histologic subtypes (P=0.011) and a higher Ki-67 index (P=0.003). Patients with neither mutation tended to be more RAI-avid than those with the BRAFV600E mutant alone or both mutations (P=0.001, <0.001, respectively). Patients with both mutations presented more unfavorable Tg response than those without both mutations and with the BRAFV600E mutant alone (P=0.001, 0.013, respectively). Tg progression-free survival (Tg-PFS) w as shorter in patients with TERT mutation alone than in those with neither mutation (P=0.021), and it tended to be shorter when BRAFV600E coexisted (P<0.001); however, no significant difference was observed between BRAFV600E alone and neither mutation (P=0.890).

CONCLUSIONS: Coexistence of BRAFV600E and TERT promoter mutations synergistically induce loss of RAI avidity and an undesirable Tg response in DM-DTC. TERT promoter mutation appears to affect Tg response more than the BRAFV600E mutation.

PMID:34890787 | DOI:10.1016/j.eprac.2021.12.005

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Motivation to smoking cessation in head and neck cancer and dysplasia patients in confrontation with the attitudes of otorhinolaryngologists in delivering anti-smoking therapies

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Eur Arch Otorhinolaryngol. 2021 Dec 10. doi: 10.1007/s00405-021-07209-2. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of the study was to determine the influence of oral, oropharyngeal, laryngeal and hypopharyngeal dysplasia and cancer diagnosis on motivation to smoking cessation in patients. Consecutively, we assessed the competence of ENT specialists in counseling anti-smoking therapies.

METHODS: Questionnaire of expected support, Schneider motivation test and Fagerström Test for Nicotine Dependence (FTND) were administered to 50 smoking patients. The online survey was collected from 152 ENT doctors.

RESULTS: Mean FTND score was 4.58 and Heaviness of Smoking Index (HSI) was 3.1. Patients with oral cavity and oropharyngeal cancer showed the greatest dependence to nicotine 7.67 and 5.25, respectively, and with hypopharyngeal cancer had the lowest 3.5, (p = 0.039). The ranges of HSI were significantly higher for youn ger patients (p = 0.036). 35 patients were adequately motivated to quit smoking, and their mean age was statistically higher (p = 0.05). Self-reported motivation to smoking cessation was 76%. Of 152 surveyed doctors, only 39% declared knowledge of the diagnostic and therapeutic cessation interventions. 75% showed interest in the training programs.

PMID:34893934 | DOI:10.1007/s00405-021-07209-2

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Timing of Acoustic Hearing Changes After Cochlear Implantation

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Objectives/Hypothesis

To determine the timing of acoustic hearing changes among hearing preservation Cochlear implant (CI) recipients. To determine differences in hearing outcomes based on device type and demographic factors. To determine if there is a relationship between the extent of early hearing loss after CI and the subsequent rate of continued hearing loss.

Study Design

Prospective, single subject study.

Methods

Two hundred and eleven subjects who received a hearing preservation CI were included in the study—80 Nucleus Hybrid L24 (Cochlear), 47 422/522 (Cochlear), 24 S8 (Cochlear), 14 S12 (Cochlear), 6 SRW (Cochlear), 21 SLIM J (Advanced Bionics), and 19 Flex (Med-EL). Of these, 127 were included in the subsequent analyses. Audiometric thresholds (low frequency pure-tone-averages) were collected and compared pre and postoperatively.

Results

Long-term hearing preservation rates were 65% (52/80) for L24, 83% (20/24) for S8, 79% (11/14) for S12, 83% (5/6) for SRW, 54% (25/47) for 422/522, 91% (21/23) for SLIM J, and 84% (16/19) for Flex. Hearing loss was not related to device type (P = .9105) or gender (P = .2169). Older subjects (age ≥65) had worse hearing outcomes than younger subjects after initial device activation (age <65, P = .0262). There was no significant difference in rate of hearing loss over time between older and younger patients (P = .0938). Initial postoperative hearing loss was not associated with the rate of long-term hearing loss.

Conclusions

Long-term low frequency hearing preservation is possible for CI recipients and is not associated with gender or device type. Rate of hearing loss over time is not dependent on patient age. Early hearing loss after CI does not predict the rate of long-term hearing loss.

Level of Evidence

3 Laryngoscope, 2021

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Mucosal Epithelial Preservation of Free Nasal Grafts Depending on the Recipient Site

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Objectives/Hypothesis

Reconstruction of mucosal defects using free mucosal grafts has become a common procedure during endoscopic sinus surgery. Epithelialization of mucosal grafts affects postoperative complications and outcomes, which could be influenced by different recipient tissue. However, morphological changes occurring in the grafts transplanted over different tissues remain unexplored.

Study Design

An animal study.

Methods

Free mucoperichondrial grafts were prepared from the nasal septum of rabbits; the cartilage group had reconstruction on the nasal septal cartilage, and the perichondrium group had reconstruction on the contralateral perichondrium. The nasal septum was removed after 1 and 4 weeks of reconstruction, and the graft was histologically evaluated.

Results

After 1 week of reconstruction, the mucosal epithelium of grafts in the cartilage group disappeared, whereas the columnar epithelium of grafts was preserved in the perichondrium group. After 4 weeks of reconstruction, the mucosal defect site was covered with mucosal epithelium in both groups. However, while squamous epithelium was mostly observed in the cartilage group, columnar epithelium containing the healthy ciliary and goblet cells was observed in the perichondrium group. Statistically significant differences were detected in the parameters of epithelial morphology between the two groups, which were higher in the perichondrium group.

Conclusions

In the reconstruction of mucosal defects using free mucosal grafts, difference in recipient tissue affects the graft epithelial morphology.

Level of Evidence

NA Laryngoscope, 2021

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Lipoinjection for Unilateral Vocal Fold Paralysis Treatment: A Systematic Review and Meta‐Analysis

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Introduction

Lipoinjection is one of the available treatments for unilateral vocal fold paralysis.

Objective

To evaluate lipoinjection predictability, and analyze the differences in safety and efficacy of the different techniques.

Study Design

Systematic review and meta-analysis.

Methods and Results

A systematic review on Medline, Cochrane, and Scopus databases included 49 articles analyzing the data of 1,166 patients, concerning technical details and voice parameters changes. Lipoinjection used a mean volume of 1.3 mL, 95% confidence interval (CI) (0.92, 1.69)—average overcorrection of 30%. Meta-analysis of pre- and postoperative voice parameters' means showed a significant improvement at 6 months of mean phonation time (preoperative: 5.12, 95% CI [4.48, 5.76]—6 months: 10.46, 95% CI [9.18, 11.75]), Jitter (preoperative: 2.71, 95% CI [2.08, 3.33])—6 months: 1.37, 95% CI [1.05, 1.70]), Shimmer (preoperative: 4.55, 95% CI [3.04, 6.07]—6 months: 2.57, 95% CI [1.69, 3.45]), grade (preoperative: 2.15, 95% CI [1.73, 2.57]—6 months: 0.12, 95% CI [0.97, 1.43]), breathiness (preoperative: 2.012, 95% CI [1.48, 2.55]—6 months: 0.99, 95% CI [0.58, 1.40]), and asthenia (preoperative: 1.90, 95% CI [1.33, 2.47]—6 months: 0.75, 95% CI [0.17, 1.33]) of GRBAS (Grade, Roughness, Breathiness, Asthenia and Strain), and Voice Handicap Index-30 (preoperative: 72.06, 95% CI [54.35, 89.76]—6 months: 26.24, 95% CI [19.58, 32.90]). Subgroup analysis by harvesting technique concluded in no statistically significant difference between them. Few complications were reported. Reintervention was only required for 86 patients.

Conclusion

Lipoinjection seems a safe therapeutic option for unilateral vocal fold paralysis, with available data showing an efficacy lasting 6 months to 1 year. Laryngoscope, 2021

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Small plaque psoriasis re‐visited: A type of psoriasis mediated by a type‐I interferon pathway

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Abstract

TNFα-inhibitor-induced psoriasis is mediated by the type-I interferon pathway, of which IFNα, LL37 and IL-36γ are major players. A subset of patients treated with TNFα inhibitors develop small plaque psoriatic lesions. Small plaque psoriasis is similarly observed in patients on immune-checkpoint inhibitors (ICI), and with concurrent systemic lupus erythematosus (SLE) or positive antinuclear antibody (ANA). Small plaque psoriasis is also the predominant phenotype in Asian populations. The association between small plaque psoriasis morphology in various clinical scenarios and the type-I interferon pathway has not been previously studied. A cross-sectional study was conducted of patients who developed small plaque psoriasis and had a biopsy for diagnostic clarification between 2009 to 2017. We obtained skin specimens from 14 adults with small plaque psoriasis; 4 patients taking anti-TNFα treatment, 4 patients with antecedent SLE, 3 patients with concurrent ANA positivity and 3 p atients taking ICI. Controls included three patients with chronic plaque psoriasis. Histology confirmed psoriasiform epidermal hyperplasia with focal lichenoid and spongiotic features. Immunohistochemical analysis revealed higher expression of IFNα-induced MXA, LL37, IL-36γ in all clinical scenarios of small plaque psoriasis compared to chronic plaque psoriasis. There was decreased CD8 T-cell migration to the epidermis and variability in the number of LAMP3+ cytoplasmic dendritic cells in the dermis of small plaque psoriasis. The findings suggest that small plaque psoriasis is a unique type of psoriasis with a distinct morphology and immune-phenotype, primarily mediated by the type-I interferon pathway. Associating morphology and disease pathogenesis, may help identify therapeutic targets for better disease control.

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