Κυριακή 21 Νοεμβρίου 2021

An integrative multi‐omic analysis reveals a major metabolic rewiring between baby foreskin keratinocytes and adult female abdominal keratinocytes.

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Abstract

Even though its development starts early in utero, neonatal skin is still immature at birth relative to adult and undergoes a maturation process extending to the first years of life. It is now established that the stratum corneum is thinner and dryer, and that skin contains less natural moisturizing factors and lipids in newborns compared to children and adults. Moreover, it has been shown that skin surface area expansion is not linear throughout life and is peaking perinatally, suggesting that baby skin has a higher epidermal cellular turnover.

Despite growing resources showing differences between adult and infant skin physiology, molecular and metabolic specificities of baby skin are still poorly understood. To address this critical knowledge gap, we performed an integrative transcriptomic and metabolomic study comparing human primary foreskin and abdominal keratinocytes from male babies and female adults, respectively.

Based on state-of-the-art integrative frameworks, our analyses revealed a major shift in the global energetic metabolism in baby foreskin keratinocytes compared to adult abdominal keratinocytes, highlighting increased amino acid metabolism and mitochondrial oxidative phosphorylation in baby cells to fuel the citric acid cycle, while showing glycolysis as the major cell energy source in adult cells.

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Gene expression profiling of laminin α3 blocked keratinocytes reveals an immune‐independent mechanism of blistering

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Abstract

Laminin-332 pemphigoid is a rare and chronic autoimmune blistering disease which results in subepidermal blisters and erosive lesions predominantly localized to mucous membranes. As histologic inflammation is variable, and non-complement fixing IgG antibodies against laminin-332 are the predominant class of autoantibodies deposited at the epidermal basement membrane zone, we hypothesized that complement-independent pro-inflammatory and blistering pathways existed similarly to that previously shown in BP. As autoantibodies to laminin α3 are most prevalent, we studied the major cellular response to blockade of laminin α3 using a well characterized monoclonal antibody (P3H9-2). RNA-seq revealed upregulation of numerous desmosomal genes (DSG1, DSG3, DSC1, DSC3, DSP) as well as KRT1 and KRT10. Additionally, P3H9-2 treated cells demonstrated downregulation of most hemidesmosomal genes. A pro-inflammatory response was not appreciated. Using pharmacological inhibito rs, we identified both protein kinase C and NOTCH as key regulators of P3H9-2 induced differentiation. We lastly utilized 3D human skin equivalents to determine whether blockade of laminin α3 would lead to delayed blistering, consistent with keratinocyte differentiation. Significant blistering was noted after 72 hours of treatment, with only minimal separation at 24 hours. In summary, blockade of laminin α3 alters keratinocyte differentiation, representing a potential complement-independent mechanism of blistering.

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Misconceptions about paraoxonase-1

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Braz J Otorhinolaryngol. 2021 Oct 26:S1808-8694(21)00171-3. doi: 10.1016/j.bjorl.2021.08.009. Online ahead of print.

NO ABSTRACT

PMID:34794918 | DOI:10.1016/j.bjorl.2021.08.009

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Petrous Bone Cholesteatoma: Facial and Hearing Preservation

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Ear Nose Throat J. 2021 Nov 19:1455613211056554. doi: 10.1177/01455613211056554. Online ahead of print.

ABSTRACT

Objectives: Petrous bone cholesteatoma (PBC) is a rare condition of the petrous portion of the temporal bone. Treatment of choice consists of radical surgical removal, paying attention to protect the facial nerve and inner ear as far as possible. The aim of the present study was to evaluate the efficacy of modified translabyrinthine techniques in preserving hearing function and the use of the adjuvant endoscopic techniques in a group of PBC patients. Methods: This study comprised 16 cases of PBCs surgically treated in our Department. Pre- and post-operative hearing status was assessed with pure tone audiometry and speech discrimination and graded according to the Gardner- Robertson classification system. Facial function was based on the House Brackman (HB) classification. PBCs were grouped using Sanna's classification. The choice of surgical technique was based on the above findings together with preoperative evidence. Post-operative follow-up ranged from 1 to 10 years and also included Computed Tomography and Magnetic Resonance Imaging assessment. Results: PBCs were classified as follows: 37.5% infralabyrinthine; 43.75% supralabyrinthine; and 18.75% massive. Preservation of the bone conduction threshold was feasible in 62.5% of patients. For supralabyrinthine PBCs a subtotal petrosetomy was performed in all cases and he aring preservation was possible in 57% of them: an adjuvant endoscopic approach was performed in 43%. Infralabyrinthine PBCs were treated using a modified translabyrinthine approach with preservation of bone conduction in 83% of patients; an adjuvant endoscopic approach was performed in 50% cases. One patient with a massive cholesteatoma was treated by modified translabyrinthine approach, preserving a serviceable level of hearing. In all massive cases, an adjuvant endoscopic approach was performed. In 2 patients with preoperative palsy, facial nerve function showed an improvement. The follow-up period revealed evidence of limited recurrence at CT imaging in 2 patients. Conclusions: The introduction of modified surgical approaches, able to preserve the anatomical-functional structures, have shown an improvement of post-operative hearing outcomes.

PMID:34797992 | DOI:10.1177/01455613211056554

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Is there a change in P300 evoked potential after 6 months in cochlear implant users?

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Braz J Otorhinolaryngol. 2021 Nov 10:S1808-8694(21)00182-8. doi: 10.1016/j.bjorl.2021.10.002. Online ahead of print.

ABSTRACT

OBJECTIVE: There are few studies on long-latency auditory evoked potential (P300) in people with hearing loss who use a cochlear implant. Central auditory system evaluation with behavioral and electrophysiological tests is believed to help understand the neuroplasticity mechanisms involved in auditory functioning after cochlear implant surgery. This study investigated the electrophysiological processing of cortical level acoustic signals in a group of 21 adult individuals with postlingual bilateral severe-to-profound hearing loss who were submitted to cochlear implant surgery.

METHODS: Data were collected in three phases: pre-cochlear implant surgery, at cochlear implant activation, and 6 months after surgery. P300 measures were also registered during all phases. Tone-burst and speech stimuli were used to elicit P300 and were presented in free field.

RESULTS: Mean P3 component latency with tone-burst and speech stimuli were 352.9 and 321.9 ms in the pre-cochlear implant phase, 364.9 and 368.7 ms in the activation phase, 336.2 and 343.6 ms 6 months after the surgery. The P3 component mean latency values using tone-burst at activation were significantly different from those 6 months after cochlear implant. They were also significantly different using speech, between pre-cochlear implant and activation phases. Lower P3 component latency occurred 6 months after cochlear implant activation with tone-burst and pre-cochlear implant with speech stimulus. There was a weak correlation between mean P3 component latency with speech stimulus and time of hearing loss. There was no difference in amplitude between phases or in the comparison with the other variables.

CONCLUSION: There were changes in P3 component latency during the period assessed, for both speech and pure-tone stimuli, with increased latency in the activation phase and similar lower results in the two other phases, Pre-CI and 6 months after CI use. Mean amplitude measures did not vary in the three phases.

PMID:34799269 | DOI:10.1016/j.bjorl.2021.10.002

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Effects of vestibular rehabilitation in the management of patients with and without vestibular migraine

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Braz J Otorhinolaryngol. 2021 Oct 25:S1808-8694(21)00161-0. doi: 10.1016/j.bjorl.2021.07.011. Online ahead of print.

ABSTRACT

OBJECTIVE: Vestibular Migraine (VM) is the second most common cause in patients with vertigo. Patients with VM complain about vestibular symptoms during a headache attack or during the period between attacks. Vestibular Rehabilitation (VR), an exercised based therapy to treat dizziness and balance dysfunction has been shown to be effective in vestibular diseases. In this study, we aimed to assess the effect of VR for vestibular symptoms and quality of life in VM patients, and to compare the results with patients with vestibular disorders without migraine.

METHODS: Sixty (60) patients who received VR treatment were divided into two groups: vestibular migraine group (30 patients) and non-migraine vestibular dysfunction group (30 patients). All patients received VR for 18 sessions and the program was complete d in 1.5 months. Pre- and post-treatment Dizziness Handicap Inventory (DHI) scores, Vestibular Disorders Activities of Daily Living Scale (VADL) scores, the frequency of dizziness and headache, and Computerized Dynamic Posturography (CDP) scores were assessed and compared retrospectively.

RESULTS: With VR in both the vestibular migraine group and vestibular dysfunction group, DHI score, VADL score, the frequency of dizziness and headache scores significantly impaired. Post-treatment CDP results were higher than pre- treatment results for both patient groups.

CONCLUSION: With VR, a significant improvement was observed in subjective and objective balance assessment measurement. Vestibular Rehabilitation must be considered in patients who do not benefit from medical therapy or have limited benefit.

LEVEL OF EVIDENCE: Level III (evidence obtained from well-designed controlled trials without randomization).

PMID:34799267 | DOI:10.1016/j.bjorl.2021.07.011

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Navigation and non-navigation CT scan of the sinuses: comparison of the effective doses of radiation in children and adults

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J Otolaryngol Head Neck Surg. 2021 Nov 19;50(1):66. doi: 10.1186/s40463-021-00541-x.

ABSTRACT

BACKGROUND: The advent of 3D navigation imaging has opened new borders to the endoscopic surgical approaches of naso-sinusal inflammatory and neoplastic disease. This technology has gained in popularity among otolaryngologists for endoscopic sinus and skull base surgeries in both adults and children. However, the increased tissue radiation required for data acquisition associated with 3D navigation protocols CT scans is a source of concern because of its potential health hazards. We aimed to compare the effective doses of radiation between 3D navigation protocols and standard protocols for sinus computed tomography (CT) scans for both the adult and pediatric population.

METHODS: We performed a retrospective cohort study through electronic chart review of patients undergoing sinus CT scans (standard and 3D navigation protocols) from May 2019 to December 2019 using a Siemens Drive (VA62A) CT scanner. The effective dose of radiation was calculated in mSv for all exams. Average irradiation doses were compared using a Student's T-Test or a Kruskall-Wallis test when appropriate.

RESULTS: A total of 115 CT scans were selected for analysis, of which 47 were standard protocols and 68 were 3D navigation protocols CT scans. Among these, 31 exams were performed on children and 84 exams on adults. For the total population, mean effective dose in the non-navigation CT scans was 0.37 mSv (SD: 0.16, N = 47) and mean effective dose in the 3D navigation sinus CT group was 2.33 mSv (SD: 0.45, N = 68). The mean difference between the two groups was statistically significant 1.97 mSv (CI 95% - 2.1 to - 1.83; P < 0.0001). There was a sixfold increase in radiation with utilization of 3D navigation protocols. The ratio was identical when the pediatric as well as the adult subset of patients were analyzed.

CONCLUSION: In our center , utilization of 3D navigation sinus CT protocols significantly increases radiation exposure. Otolaryngologists should be aware of this significant increase and should attempt to decrease the radiation exposure of their patients by limiting unnecessary scan orders and by evaluating 3D acquisition protocols locally with radiation physicists.

LEVEL OF EVIDENCE: Level IV.

PMID:34798901 | DOI:10.1186/s40463-021-00541-x

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A systematic review and meta-analysis of the effects of intraoral treatments for neurogenic oropharyngeal dysphagia

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J Oral Rehabil. 2021 Nov 20. doi: 10.1111/joor.13274. Online ahead of print.

ABSTRACT

BACKGROUND: Rehabilitative treatments for oropharyngeal dysphagia, including oromotor exercises and sensory stimulation, have been widely adopted in clinical practice. However, the effects of these treatments are mainly supported by exploratory studies. As such, their clinical efficacy remains uncertain.

OBJECTIVE: Our systematic review and meta-analysis aimed to evaluate the efficacy of int raoral treatments for neurogenic oropharyngeal dysphagia based on evidence from randomised controlled trials (RCTs).

METHODS: Six electronic databases were systematically searched between January 1970 and July 2021. Data were extracted and analysed by two independent reviewers. The outcome measure was change in (any) relevant clinical swallowing-related characteristic.

RESULTS: Data from 285 dysphagic patients were collected from 8 RCT studies across a range of intraoral dysphagia treatments. The pooled effect size of all intraoral dysphagia treatments was non-significant compared to control comparators (SMD [95%CI] = 0.23 [-0.22, 0.69], p=0.31; I2 =73%). Subgroup analysis revealed that the pooled effect sizes were also non-significant for oromotor exercises (device-facilitated lip resistance exercises and tongue exercises) (SMD [95%CI] = 0.11 [-0.76, 0.97]; p=0.81; I2 =88%) and sensory stimulation (thermal-tactile, thermo-chemical and electrical st imulation) (SMD [95%CI] = 0.35 [-0.03, 0.72]; p=0.07; I2 =0%).

CONCLUSIONS: Our results showed that overall, intraoral dysphagia treatments, including oromotor exercises and sensory stimulation, do not show beneficial effects for neurogenic oropharyngeal dysphagia. The evidence for these treatments remains weak and currently inadequate to support clinical use. Large scale, multi-centre randomised controlled trials are warranted to fully explore their clinical efficacy.

PMID:34800341 | DOI:10.1111/joor.13274

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Anatomical variants of the medioplantar oblique ligament and inferoplantar longitudinal ligament: an MRI study

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Surg Radiol Anat. 2021 Nov 20. doi: 10.1007/s00276-021-02860-0. Online ahead of print.

ABSTRACT

PURPOSE: The spring ligament complex (SL) is the chief static stabilizer of the medial longitudinal foot arch. The occurrence of normal anatomical variants may influence radiological diagnostics and surgical treatment. The aim of this study was to evaluate anatomical variants of the part of SL located inferior to the talar head (i-SL), medioplantar oblique ligament (MPO) and infer oplantar longitudinal ligament (IPL).

METHODS: We included 220 MRI examinations of the ankle performed on a 3.0 T engine. Only patients with a normal SL were included. Two musculoskeletal radiologists assessed the examinations and Cohen's kappa was used to assess agreement. Differences between groups were assessed using the chi-squared test; p < 0.05 was considered as significant. The final decision was made by consensus.

RESULTS: Most commonly, i-SL was composed of the two ligaments IPL and MPO n = 167 (75.9%); in this group, bifid ligaments occurred in 19.2%, most commonly in the MPO. A branch to the os cuboideum was seen in n = 17 (10.2%). Three ligaments were seen in n = 52 (23.6%). In this group, bifid ligaments occurred in 13.5%; most commonly, the IPL was bifid and a branch to the os cuboideum was noted in n = 6 (11.5%). In one case, n = 1 (0.04%), we identified MPO, IPL and two accessory ligaments. No significant relationship was noted between the number of li gaments, the presence of bifid ligaments and side or gender (p > 0.05).

CONCLUSION: More than two aligaments were seen in 24.1% of examined cases, the most common variant was the presence of MPO, IPL and one accessory ligament.

PMID:34800154 | DOI:10.1007/s00276-021-02860-0

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Circadian clock and cell cycle: Cancer and chronotherapy

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Via histochem

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Acta Histochem. 2021 Nov 17;123(8):151816. doi: 10.1016/j.acthis.2021.151816. Online ahead of print.

ABSTRACT

The circadian clock is an endogenous timing system that ensures that various physiological processes have nearly 24 h circadian rhythms, including cell metabolism, division, apoptosis, and tumor production. In addition, results from animal models and molecular studies underscore emerging links between the cell cycle and the circadian clock. Mutations in the core gene s of the circadian clock' can disrupt the cell cycle, which in turn increases the possibility of tumors. At present, tumor chronotherapy, which relies on a circadian clock mechanism, is developing rapidly for optimizing the time of drug administration in tumor treatment to improve drug efficacy and safety. However, the relationship between the circadian clock and the cell cycle is extremely complicated. This review summarizes the possible connection between the circadian clock and the cell cycle. In addition, the review provides evidence of the influence of the circadian clock on senescence and cancer.

PMID:34800857 | DOI:10.1016/j.acthis.2021.151816

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