Κυριακή 18 Απριλίου 2021

Effects of metformin on experimentally induced acne on rabbit ear

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Abstract

Evidence for the effectiveness of metformin in the treatment of acne is limited. To assess its efficacy, comedones were experimentally induced in young New Zealand rabbit ear using Isopropyl Myristate (IM) followed by metformin treatment (30 mg/kg bodyweight) for 60 days with continued IM application. In another group, to check whether metformin pre‐treatment affects subsequent comedone development by IM, metformin was given for 14 days and then withdrawn (14 days) followed by comedone development with IM and metformin treatment. At different time points, dermatoscopic images of rabbit ear were taken for clinical assessment. Blood and biopsy samples were taken for hormonal assessment, histological examination and gene expression. Histologically confirmed acne model was developed in rabbit ear. Follicular size increased significantly (p = 0.0004 in both groups) upon IM application. Metformin significantly decreased comedones size as observed i n dermatoscopic (p = 0.0003 in group I, p = 0.0190 in group II) and histological examination (p = 0.0313 in group I and II). However, size of comedones developed after metformin pretreatment was significantly (p < 0.0001) smaller. The lipid content of sebaceous glands decreased with metformin without any significant changes in the assessed hormones and genetic expression. Overall, metformin was found to be clinically effective in experimentally induced acne and can be used in humans.

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5‐Aminolaevulinic acid photodynamic therapy amplifies intense inflammatory response in the treatment of acne vulgaris via CXCL8

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Abstract

Acne vulgaris is a chronic inflammatory cutaneous disease. 5‐Aminolaevulinic acid photodynamic therapy (ALA‐PDT) is a novel and effective approach for severe acne vulgaris treatment. However, its specific treatment mechanism still remains unclear. In the present study, we investigated the potential mechanism of how ALA‐PDT regulated intense inflammatory response in acne vulgaris. It appeared that ALA‐PDT suppresses proliferation and lipid secretion of primary human sebocytes. Besides, ALA‐PDT could up‐regulate the expression of CXCL8 in vivo and in vitro, amplifying the inflammatory response by recruiting T cells, B cells, neutrophils and macrophages. We also found that ALA‐PDT elevated the expression of CXCL8 via p38 pathway. SB203580, a p38 pathway inhibitor, decreased the expression of CXCL8 in sebocytes after ALA‐PDT. These findings indicate that ALA‐PDT amplifies the intense inflammatory response in treatment of acne vulgaris via CXCL8. Our data deciphers th e mechanism of intense inflammatory response after ALA‐PDT for acne vulgaris.

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Superficial Siderosis: A Clinical Review

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Ann Neurol. 2021 Apr 15. doi: 10.1002/ana.26083. Online ahead of print.

ABSTRACT

Superficial siderosis of the central nervous system results from subpial hemosiderin deposition due to chronic low-grade bleeding into the subarachnoid space. The confluent and marginal subpial hemosiderin is best appreciated on iron-sensitive magnetic resonance imaging sequences. With widespread use of magnetic resonance imaging, the disorder is increasingly being recognized, including in asymptomatic individuals. Gait ataxia, often with hearing impairment is a common clinical presentation. A clinical history of subarachnoid hemorrhage is generally not present. A macrovascular pathology is generally not causative. The most common etiology is dural disease, often dural tears. Prior or less commonly ongoing symptoms of craniospinal hypovolemia may be present. Common etiologies for dural tears include disc disease and trauma, including surgical trauma. Patients wit h dural tears due to herniated and calcified discs often have a ventral intraspinal fluid collection due to cerebrospinal fluid leak. A precise identification of the dural tear relies on multi-modality imaging. It has been speculated that chronic bleeding from fragile blood vessels around the dural tear may be the likely underlying mechanism. Surgical correction of the bleeding source is a logical therapeutic strategy. Clinical outcomes are variable though neuroimaging evidence of successful dural tear repair is noted. The currently available data regarding use of deferiprone in patients with superficial siderosis is insufficient to recommend its routine use in patients. This article is protected by copyright. All rights reserved.

PMID:33860558 | DOI:10.1002/ana.26083

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Age-related hearing loss, depression and auditory amplification: a randomized clinical trial

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Eur Arch Otorhinolaryngol. 2021 Apr 16. doi: 10.1007/s00405-021-06805-6. Online ahead of print.

ABSTRACT

PURPOSE: Our study investigates the effectiveness of aural rehabilitation to decrease depressive symptoms in older adults, and the relationship between hearing loss and depression.

METHODS: A randomized controlled study was conducted at a hearing rehabilitation center with people over 65 years old. Participants were randomly allocated to the intervention group who received hearing aids, or to the control group. Data collection included pure-tone audiometry and a Portuguese version of the Geriatric Depression Scale assessed at two time points: baseline (P0) and after 4-week period (P1).

RESULTS: The results show that the increase of hearing thresholds in pure-tone audiometry is associated with a significant increase in depressive symptoms (p = 0.001). The effect of aural rehabilitation for improving depressive symptoms wa s significant in intervention group (p = 0.000) and between groups (p = 0.003) in P1.

CONCLUSION: Age-related hearing loss has adverse effects on older adults' mental health, due to reduced hearing inputs that may increase levels of effort to communicate and affect social engagement, which lead to depression. Hearing aid use improves levels of depression and can promote greater quality of life in older adults.

PMID:33860839 | DOI:10.1007/s00405-021-06805-6

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Effect of smoking status and programmed death-ligand 1 expression on the microenvironment and malignant transformation of oral leukoplakia: A retrospective cohort study

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journal.pone.0250359.g002&size=inline

by Takahiro Yagyuu, Naoki Funayama, Mitsuhiko Imada, Tadaaki Kirita

Tobacco smoking is associated with an increased risk of oral leukoplakia and head and neck cancer. Although it has recently been reported that the establishment of an immunosuppressive microenvironment in oral potentially malignant disorders may lead to malignant transformation, it is unclear whether the microenvironments of oral potentially malignant disorders differ according to smoking status. We examined differences in programmed death-ligand 1 (PD-L1) expression and subepithelial CD163+ TAM and CD8+ cell/lymphocyte counts in the microenvironment of oral leukoplakia of smoking and non-smoking patients and investigated their associations with malignant transformation. Pathology reports and original biopsy request forms from 1995–2015 were retrospectively reviewed. Lesions clinically characterized as white plaques/lesions of the oral mucosa and pathologically diagnosed as oral epithelial dysplasia were included. Immunohistochemistry was performed to evaluate PD-L1 expression and subepithelial CD163+/CD8+ cell counts. The significance of prognostic factors in predicting malignant transformation was determined using Cox regression analysis. Statistical significance was defined as P
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Auditory Brainstem Models: Adapting Cochlear Nuclei Improve Spatial Encoding by the Medial Superior Olive in Reverberation

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Abstract

Listeners typically perceive a sound as originating from the direction of its source, even as direct sound is followed milliseconds later by reflected sound from multiple different directions. Early-arriving sound is emphasised in the ascending auditory pathway, including the medial superior olive (MSO) where binaural neurons encode the interaural-time-difference (ITD) cue for spatial location. Perceptually, weighting of ITD conveyed during rising sound energy is stronger at 600 Hz than at 200 Hz, consistent with the minimum stimulus rate for binaural adaptation, and with the longer reverberation times at 600 Hz, compared with 200 Hz, in many natural outdoor environments. Here, we computationally explore the combined efficacy of adaptation prior to the binaural encoding of ITD cues, and excitatory binaural coincidence detection within MSO neurons, in emphasising ITDs conveyed in early-arriving sound. With excitatory inputs from adapting, nonlinear model spherical bushy cells (SBCs) of the bilateral cochlear nuclei, a nonlinear model MSO neuron with low-threshold potassium channels reproduces the rate-dependent emphasis of rising vs. peak sound energy in ITD encoding; adaptation is equally effective in the model MSO. Maintaining adaptation in model SBCs, and adjusting membrane speed in model MSO neurons, 'left' and 'right' populations of computationally efficient, linear model SBCs and MSO neurons reproduce this stronger weighting of ITD conveyed during rising sound energy at 600 Hz compared to 200 Hz. This hemispheric population model demonstrates a link between strong weighting of spatial information during rising sound energy, and correct unambiguous lateralisation of a speech source in reverberation.

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Super-enhancer Acquisition Drives FOXC2 Expression in Middle Ear Cholesteatoma

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Abstract

Distinct histone modifications regulate gene expression in certain diseases, but little is known about histone epigenetics in middle ear cholesteatoma. It is known that histone acetylation destabilizes the nucleosome and chromatin structure and induces gene activation. The association of histone acetylation with chronic inflammatory diseases has been indicated in recent studies. In this study, we examined the localization of variously modified histone H3 acetylation at lysine 9, 14, 18, 23, and 27 in paraffin-embedded sections of human middle ear cholesteatoma (cholesteatoma) tissues and the temporal bones of an animal model of cholesteatoma immunohistochemically. As a result, we found that there was a significant increase of the expression levels of H3K27ac both in human cholesteatoma tissues and the animal model. In genetics, super-enhancers are clusters of enhancers that drive the transcription of genes involved in cell identity. Super-enhancers were originall y defined using the H3K27ac signal, and then we used H3K27ac chromatin immunoprecipitation followed by sequencing to map the active cis-regulatory landscape in human cholesteatoma. Based on the results, we identified increased H3K27ac signals as super-enhancers of the FOXC2 loci, as well as increased protein of FOXC2 in cholesteatoma. Recent studies have indicated that menin-MLL inhibitor could suppress tumor growth through the control of histone H3 modification. In this study, we demonstrated that the expression of FOXC2 was inhibited by menin-MLL inhibitor in vivo. These findings indicate that FOXC2 expression under histone modifications promoted the pathogenesis of cholesteatoma and suggest that it may be a therapeutic target of cholesteatoma.

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Role of VDR gene polymorphisms with community acquired pneumonia in North Indian children: a case-control study

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Int J Mol Epidemiol Genet. 2021 Feb 15;12(1):1-8. eCollection 2021.

ABSTRACT

Community-acquired pneumonia (CAP) is a leading cause of death in children under five years of age globally. Currently, the vitamin D receptor (VDR) gene is an emerging factor that regulates inflammatory pathways that may alter the response to infections and possibly modify the outcome of CAP. The objective of this study was to investigate the association of VDR gene polymorphisms ApaI, FokI, TaqI, BsmI with CAP in children aged 2-59 months. Hospitalized children aged (2-59 months) with WHO-defined CAP were included as cases after parental consent. Age-matched healthy controls were recruited from the immunization clinic of the hospital within one week of the recruitment of the case. Children with a clinical diagnosis of cystic fibrosis and congenital heart disease were excluded. Four VDR gene polymorphisms, ApaI, FokI, TaqI, BsmI were genotyped by using PCR-RFLP. From Oct-2016 to Oct-2019, 160 cases (34.37% females) and 160 controls (47.5% females) were recruited. Mean age of the cases was 26.30±23.10 months and controls 25.93±15.99 months. In FokI (rs2228570 polymorphism, heterozygous genotype (CT) [OR=2.06, 95% CI=1.25-3.39, P=0.00] and mutant allele (T) [OR=1.45, 95% CI=1.06-2.00, P=0.02] were found to be associated with the risk of CAP. In VDR gene, FokI polymorphism predisposes to CAP in Indian children.

PMID:33859782 | PMC:PMC8044708

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Reconstruction of Plasmodium vivax outbreaks in a low malaria endemic setting utilizing conventional restriction fragment length polymorphism

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Int J Mol Epidemiol Genet. 2021 Feb 15;12(1):9-15. eCollection 2021.

ABSTRACT

Suriname is on track to eliminate local malaria transmission. P. vivax malaria reemerged in March and September 2019 in the Amerindian village Palumeu, free of malaria for two years and concurrently, a case was reported in another village Alalaparoe. The outbreaks were contained through targeted interventions including Mass Drug Administration (MDA). Molecular outbreak analysis was performed on 23 dried blood spots (DBS) using combined polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) with Pvmsp-1 F2 and Pvmsp-3α as polymorphic marker genes. Independent controls substantiated the discriminating capacities of the utilized PCR-RFLP method. All isolates from the first and second Palumeu outbreak shared a distinctive haplotype presuming single clonal lineage. An imported case probably triggered the first outbreak, while a delayed episode, prompted by withdrawal of drug pressure at the end of the prophylactic MDA, was suggested as source of the second outbreak. A diverging variant was demonstrated in Alalaparoe, implicating an infection from a different source. PCR-RFLP proved to be a useful molecular tool for P. vivax outbreak management in low endemic malaria settings.

PMID:33859783 | PMC:PMC8044709

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Effect of smoking status and programmed death-ligand 1 expression on the microenvironment and malignant transformation of oral leukoplakia: A retrospective cohort study

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journal.pone.0250359.g002&size=inline

by Takahiro Yagyuu, Naoki Funayama, Mitsuhiko Imada, Tadaaki Kirita

Tobacco smoking is associated with an increased risk of oral leukoplakia and head and neck cancer. Although it has recently been reported that the establishment of an immunosuppressive microenvironment in oral potentially malignant disorders may lead to malignant transformation, it is unclear whether the microenvironments of oral potentially malignant disorders differ according to smoking status. We examined differences in programmed death-ligand 1 (PD-L1) expression and subepithelial CD163+ TAM and CD8+ cell/lymphocyte counts in the microenvironment of oral leukoplakia of smoking and non-smoking patients and investigated their associations with malignant transformation. Pathology reports and original biopsy request forms from 1995–2015 were retrospectively reviewed. Lesions clinically characterized as white plaques/lesions of the oral mucosa and pathologically diagnosed as oral epithelial dysplasia were included. Immunohistochemistry was performed to evaluate PD-L1 expression and subepithelial CD163+/CD8+ cell counts. The significance of prognostic factors in predicting malignant transformation was determined using Cox regression analysis. Statistical significance was defined as P
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Surgical, clinical, and functional outcomes of transoral robotic surgery used in sleep surgery for obstructive sleep apnea syndrome: A systematic review and meta‐analysis

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Abstract

We investigated safety and efficacy of transoral robotic surgery (TORS) for base of tongue (BOT) reduction in obstructive sleep apnea syndrome (OSAS) patients. PubMed, Cochrane Library, and Scopus were searched. A meta‐analysis was performed. Random effects models were used. Thirty‐one cohorts met our criteria (1693 patients). The analysis was based mostly on retrospective studies. The summary estimate of the reduction of Apnea–Hypoxia Index (AHI) was 24.25 abnormal events per hour (95% CI: 21.69–26.81) and reduction of Epworth Sleepiness Scale (ESS) was 7.92 (95% CI: 6.50–9.34). The summary estimate of increase in lowest O2 saturation was 6.04% (95% CI: 3.05–9.03). The success rate of TORS BOT reduction, either alone or combined with other procedures, was 69% (95% CI: 64–79). The majority of studies reported low level of evidence but suggested that TORS BOT reduction may be a safe procedure associated with improvement of AHI, ESS, and lowest O2 saturation.

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