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

xlomafota13 shared this article with you from Inoreader Upregulation of TLR9 may contribute to activation of microglia and painful diabetic neuropathy via the p38 MAPK pathway in rats Via Cellular and Molecular Biology 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 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Timing of Acoustic Hearing Changes After Cochlear Implantation

xlomafota13 shared this article with you from Inoreader Timing of Acoustic Hearing Changes After Cochlear Implantation Via The Laryngoscope 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 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

xlomafota13 shared this article with you from Inoreader Lipoinjection for Unilateral Vocal Fold Paralysis Treatment: A Systematic Review and Meta‐Analysis Via The Laryngoscope 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 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

xlomafota13 shared this article with you from Inoreader Small plaque psoriasis re‐visited: A type of psoriasis mediated by a type‐I interferon pathway Via Experimental Dermatology 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. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.