A novel heterozygous variant of the SALL1 gene with atypical Townes-Brocks syndrome phenotypes in Chinese family.

Townes-Brocks syndrome (TBS) is an autosomal dominant disorder characterised by the triad of anorectal, thumb, and ear malformations. It may also be accompanied by defects in kidney, heart, eyes, hearing, and feet. TBS has been demonstrated to result from heterozygous variants in the SALL1 gene, which encodes zinc finger protein believed to function as a transcriptional repressor. The clinical characteristics of an atypical TBS phenotype patient from a Chinese family are described, with predominant manifestations including external ear dysplasia, unilateral renal hypoplasia with mild renal dysfunction, and hearing impairment. A novel heterozygous variant c.3060T>A (p.Tyr1020*) in exon 2 of the SALL1 gene was identified in this proband. Pyrosequencing of the complementary DNA of the proband revealed that the variant transcript accounted for 48% of the total transcripts in peripheral leukocytes, indicating that this variant transcript has not undergone nonsense-mediated mRNA decay. This variant c.3060T > A is located at the terminal end of exon 2, proximal to the 3' end of the SALL1 gene, and exerts a relatively minor impact on protein function. We suggest that the atypical TBS phenotype observed in the proband may be attributed to the truncated protein retaining partial SALL1 function.

Preparation of Compound Salvia miltiorrhiza-Blumea balsamifera Nanoemulsion Gel and Its Effect on Hypertrophic Scars in the Rabbit Ear Model.

Hypertrophic scars (HS) still remain an urgent challenge in the medical community. Traditional Chinese medicine (TCM) has unique advantages in the treatment of HS. However, due to the natural barrier of the skin, it is difficult for the natural active components of TCM to more effectively penetrate the skin and exert therapeutic effects. Therefore, the development of an efficient drug delivery system to facilitate enhanced transdermal absorption of TCM becomes imperative for its clinical application. In this study, we designed a compound Salvia miltiorrhiza-Blumea balsamifera nanoemulsion gel (CSB-NEG) and investigated its therapeutic effects on rabbit HS models. The prescription of CSB-NEG was optimized by single-factor, pseudoternary phase diagram, and central composite design experiments. The results showed that the average particle size and PDI of the optimized CSB-NE were 46.0 ± 0.2 nm and 0.222 ± 0.004, respectively, and the encapsulation efficiency of total phenolic acid was 93.37 ± 2.56%. CSB-NEG demonstrated excellent stability and skin permeation in vitro and displayed a significantly enhanced ability to inhibit scar formation compared to the CSB physical mixture in vivo. After 3 weeks of CSB-NEG treatment, the scar appeared to be flat, pink, and flexible. Furthermore, this treatment also resulted in a decrease in the levels of the collagen I/III ratio and TGF-ß1 and Smad2 proteins while simultaneously promoting the growth and remodeling of microvessels. These findings suggest that CSB-NEG has the potential to effectively address the barrier properties of the skin and provide therapeutic benefits for HS, offering a new perspective for the prevention and treatment of HS.

Effect of binaural beat in the inaudible band on EEG (STROBE).

This study aimed to determine the effects of the binaural beat (BB) on brainwave induction using an inaudible baseline frequency outside the audible frequency range. Experiments were conducted on 18 subjects (11 males [mean age: 25.7 ± 1.6 years] and 7 females [mean age: 24.0 ± 0.6 years]). A BB stimulation of 10 Hz was exerted by presenting frequencies of 18,000 Hz and 18,010 Hz to the left and right ears, respectively. A power spectrum analysis was performed to estimate the mean of the absolute power of the alpha frequency range (8-13 Hz). The variation in the mean alpha power during the rest and stimulation phases in each brain area was compared using the Wilcoxon signed-rank test. Compared to the rest phase, the stimulation phase with BB showed an increasing trend in the mean alpha power across all 5 brain areas. Notably, a significant increase was found in the frontal, central, and temporal areas. This is a significant study in that it determines the effects of only BB without the influence of auditory perception, which has been overlooked in previous studies.

'Reflexology: Exploring the mechanism of action'.

Reflexology is a complementary therapy focusing mainly on the application of pressure on the feet, hands and ears. A small but growing evidence base suggests that positive outcomes can be gained in the management and improvement of symptoms across a range of conditions. Biological plausibility is a key concept in the determination of the usefulness of therapies. Research which tests for safety and efficacy alongside the underpinning mechanism of action are therefore important. This paper explores the potential mechanism of action for the outcomes associated with reflexology treatment as reflected in the current evidence. The influences of therapeutic touch, relaxation, placebo effects and the similarities with other therapeutic methods of structural manipulation are considered. The lack of clarity around the precise definition of reflexology and the challenges of researching the therapy as a treatment tailored to individual need are discussed. A deeper understanding of the mechanism of action for reflexology may help to further develop research into safety and efficacy. Such an understanding may lead to the integration of knowledge which may provide both symptomatic support and longer term preventative health benefits.

Neuroauriculotherapy: Framework and Remarks for a possible use in Voice Medicine / Neuroauriculoterapia: marco y observaciones para un posible uso en medicina de la voz

Aim. Neuroauriculotherapy (NAT) is a branch of medicine, which, thanks to its diagnostic and therapeutic value, is a powerful tool at the service of both physician and patient. In our experience, as it is discussed in this article, neuroauriculotherapy can have successful applications in voice science and in phoniatrics. The aim of this article is to open a discussion about possible applications of neuroauriculotherapy in voice medicine. Introduction. From the diagnostic point of view, it is possible to explore, with a palpeur (i.e., a tool that provides a constant pressure) or a "spot-hunter", the presence of a perturbation into a particular organ or area, and its return to normal during treatment. Indeed, at the level of the ear auricle, representations of an organ, its in-nervation, its muscular components, etc., are fixed. These spots or voxels correspond absolutely to the respective sensory, motor, visceral, among other spots. Therefore, if any abnormal potential comes from the periphery, it will illuminate the spots both at the cortical level and in the pavilion ­a real display with a constantly active touch screen. The spot can be treated with needles in the context of a neurophysiological strategy to send a message to the brain.Reflection. NAT appears to be a good method to improve the treatment of voice problems, enhancing the results of other therapies based on drugs or rehab and in-ducing relaxation. In neuroauriculotherapy, the ear is used to give the brain orders in a process which has a logical basis in neurophysiology.Conclusion. Diseases of the vocal tract can be dysfunctional or organic. According to our clinical experience, we can say that neuroauriculotherapy can be used in both cases. Neuroauriculotherapy is also extremely effective in voice therapy, both alone and in combination with other therapies, as there is no conflict among them

Objetivo. La neuroauriculoterapia (NAT) es una rama de la medicina que, gracias a su valor diagnóstico y terapéutico, constituye una poderosa herramienta al servicio del médico y del paciente. En nuestra experiencia, como se comenta en este artículo, la neuroauriculoterapia puede tener aplicaciones exitosas en la ciencia de la voz y en foniatría. El objetivo de este artículo es abrir una discusión sobre las posibles aplica-ciones de la neuroauriculoterapia en la medicina de la voz.Introducción. Desde el punto de vista del diagnóstico, es posible explorar, con un palpeur (i.e., una herramienta que proporciona una presión constante) o un "spot-hunter", la presencia de una perturbación en un órgano o área en particular, y su retorno a la normalidad durante el tratamiento. En efecto, a nivel del pabellón auricular se fijan representaciones de un órgano, su inervación, sus componentes musculares, etc. Estos puntos o vóxeles corresponden absolutamente a los respectivos puntos sensoriales, motores, viscerales, entre otros. Por lo tanto, si algún potencial anormal proviene de la periferia, iluminará los puntos tanto a nivel cortical como en el pabellón ­una pantalla real con una pantalla táctil constantemente activa. El punto se puede tratar con agujas en el contexto de una estrategia neurofisiológica para enviar un mensaje al cerebro.Reflexión. NAT parece ser un buen método para mejorar el tratamiento de los problemas de voz, potenciando los resultados de otras terapias basadas en fármacos o rehabilitación e induciendo a la relajación. En neuroauriculoterapia se utiliza el oído para dar órdenes al cerebro en un proceso que tiene una base lógica en la neurofisiología.Conclusión. Las enfermedades del tracto vocal pueden ser disfuncionales u orgáni-cas. Según nuestra experiencia clínica, podemos decir que la neuroauriculoterapia se puede utilizar en ambos casos. La neuroauriculoterapia también es extremadamente eficaz en la terapia de la voz, tanto sola como en combinación con otras terapias, ya que no existe conflicto entre ellas

Anti-allergic property of 4,8-sphingadienine stereoisomers in vivo and in vitro model.

4,8-Sphingadienines (SD), metabolites of glucosylceramides (GlcCer), are sometimes determined as key mediators of the biological activity of dietary GlcCer, and cis/trans geometries of 4,8-SD have been reported to affect its activity. Since regulating excessive activation of mast cells seems an important way to ameliorate allergic diseases, this study was focused on cis/trans stereoisomeric-dependent inhibitory effects of 4,8-SD on mast cell activation. Degranulation of RBL-2H3 was inhibited by treatment of 4-cis-8-trans- and 4-cis-8-cis-SD, and their intradermal administrations ameliorated ear edema in passive cutaneous anaphylaxis reaction, but 4-trans-8-trans- and 4-trans-8-cis-SD did not. Although the activation of mast cells depends on the bound IgE contents, those stereoisomers did not affect IgE contents on RBL-2H3 cells after the sensitization of anti-TNP IgE. These results indicated that 4-cis-8-trans- and 4-cis-8-cis-SD directly inhibit the activation of mast cells. In conclusion, it was assumed that 4,8-SD stereoisomers with cis double bond at C4-position shows anti-allergic activity by inhibiting downstream pathway after activation by the binding of IgE to mast cells.

The Effect of Auricular Acupressure for Chronic Low Back Pain in Elders: A Randomized Controlled Study.

Chronic low back pain (CLBP) is a major problem throughout the world and getting worse because of population increase and aging. The cost of treatment increases as the population of people with CLBP increases. This study aimed to examine the effect of auricular acupressure (AA) on pain and disability in elders with chronic low back pain. The randomized, single-blinded, and placebo-controlled study was conducted on 51 elders with CLBP in South Korea from June 2019 to August 2019. The experimental group (n = 26) received AA on low back pain-related points, whereas the placebo control group (n = 25) received AA on points unrelated to low back pain. Participants received 6 weeks of AA in weekly cycles. Collected data were analyzed using IBM SPSS Statistics, version 25. Statistically significant differences between the 2 groups emerged in the visual analog scale (P < .001), pain threshold (P < .001), and Oswestry Disability Index (P < .001). This study showed that 6 weeks of AA improved CLBP and pain-related disability. Therefore, AA can be used as a noninvasive and self-managed alternative intervention for CLBP in older adults.

Immediate effect of non-invasive auricular acupoint stimulation on the performance and meridian activities of archery athletes: A protocol for randomized controlled trial.

BACKGROUND: Archery has existed in human history for millenniums. Being a unique exercise and precision sport, the keys to performance are emotional control, attention, and concentration rather than explosive force, muscle power, and endurance. During the execution of archery, attention is the key to performance in elite players, especially in the initial period while drawing the bow. Auricular acupoint stimulation is one of the therapeutic methods of traditional Chinese medicine and has been reported for its use in amplifying the anesthesia effect, weight reduction, cessation of substance abuse, and autonomic nervous modulation. METHODS: The study will recruit archery players in school teams among junior and senior high schools and colleges. The subjects will be randomly assigned to the ear and sham acupressure groups. This is a randomized controlled trial with crossover design. The outcome measures will be obtained, including the meridian activities and balance index with Ryodoraku device, the movement stability with WIMU tracking system, the continuous heart rate record, and the scores of the 2 sections as the performance. The subjects will rate their attention and fatigue levels through self-reported questionnaires. OBJECTIVES: This study aims to investigate the immediate effect of non-invasive auricular acupoint stimulation on the performance and meridian activities of archery athletes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04637607.

Speech-imagery-based brain-computer interface system using ear-EEG.

OBJECTIVE: This study investigates the efficacy of electroencephalography (EEG) centered around the user's ears (ear-EEG) for a speech-imagery-based brain-computer interface (BCI) system. APPROACH: A wearable ear-EEG acquisition tool was developed and its performance was directly compared to that of a conventional 32-channel scalp-EEG setup in a multi-class speech imagery classification task. Riemannian tangent space projections of EEG covariance matrices were used as input features to a multi-layer extreme learning machine classifier. Ten subjects participated in an experiment consisting of six sessions spanning three days. The experiment involves imagining four speech commands ('Left,' 'Right,' 'Forward,' and 'Go back') and staying in a rest condition. MAIN RESULTS: The classification accuracy of our system is significantly above the chance level (20%). The classification result averaged across all ten subjects is 38.2% and 43.1% with a maximum (max) of 43.8% and 55.0% for ear-EEG and scalp-EEG, respectively. According to an analysis of variance, seven out of ten subjects show no significant difference between the performance of ear-EEG and scalp-EEG. SIGNIFICANCE: To our knowledge, this is the first study that investigates the performance of ear-EEG in a speech-imagery-based BCI. The results indicate that ear-EEG has great potential as an alternative to the scalp-EEG acquisition method for speech-imagery monitoring. We believe that the merits and feasibility of both speech imagery and ear-EEG acquisition in the proposed system will accelerate the development of the BCI system for daily-life use.

Effect of Nectaroscordum koelzi Methanolic Extract on Acute and Chronic Inflammation in Male Mice.

INTRODUCTION: The present study deals with the effect of Nectaroscordum koelzi fruit extract on acute and chronic inflammation. METHODS: A total of 84 NMRI mice were used in this study. The effect of the extract on acute inflammation was analyzed by increasing vascular permeability via acetic acid and xylene induced ear edema among mice. The extract was evaluated in terms of effects on chronic inflammation by means of the cotton pellet test among mice. For the assessment of inflammation degree, the mice paw edema volume was measured by the plethysmometric test. RESULTS: The findings showed that the extract was effective on acute inflammation induced by acetic acid in mice. In the xylene ear edema, N. koelzi extract indicated a significant activity in mice. In the cotton pellet method, the methanol extract produced a significant reduction in comparison with the control and dexamethasone. Mice paw edema volume decreased with the extract. CONCLUSION: In general, the data from the experiments indicated that the methanol extract of N. koelzi has an anti-inflammatory effect on acute and chronic inflammation. However, the exact contributing mechanisms have not been investigated for the pharmacological effects.

Battlefield Acupuncture for Adult Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Pain is a major public health problem, causing heavy social and economic burdens to patients and society while consuming tremendous medical resources at the same time. Thus, there is a critical need to find low-cost, efficacious, and therapeutic approaches to help manage pain. While acupuncture is increasingly recognized as a promising pain-relieving method, less is known about a specific form of auricular acupuncture known as Battlefield Acupuncture (BFA). The BFA technique involves the sequential placement of semi-permanent, single-use, French ASP[Formula: see text] golden needles to five specific acupoints in one or both ears, where they are left in place for 3-4 days or longer [Niemtzow, R.C., Battlefield acupuncture. Med. Acupunct. 19: 225-228, 2007]. The BFA needles (more accurately described as tiny conical darts) pierce the ear in designated locations in a particular order [Levy, C.E., N. Casler and D.B. FitzGerald. Battlefield acupuncture: an emerging method for easing pain. Am. J. Phys. Med. Rehabil. 97: e18-e19, 2018.]. (Figs. 4 and 5) It was developed by Dr. Richard C. Niemtzow in 2001, as a subgroup form of an auricular acupuncture technique based on the somatotopic arrangement of an inverted fetus pattern on the external ear [Romoli, M. Ear acupuncture: historical abstract-differences of ear cartography between the east and the west. Dtsch. Z. Akupunkt. 53: 24-33, 2010.]. Currently, BFA is widely used in the US military, but to our knowledge, there is no review which comprehensively synthesizes the current publications surrounding pain management. This review aims to investigate the effects and safety of BFA in adults with pain. Electronic databases were searched for randomized controlled trials (RCTs) published in English evaluating efficacy and safety of BFA in adults with pain, from database inception to September 6, 2019. The primary outcome was pain intensity change, and the secondary outcome was safety. Nine RCTs were included in this review, and five trials involving 344 participants were analyzed quantitatively. Compared with no intervention, usual care, sham BFA, and delayed BFA interventions, BFA had no significant improvement in the pain intensity felt by adults suffering from pain. Few adverse effects (AEs) were reported with BFA therapy, but they were mild and transitory. BFA is a safe, rapid, and easily learned acupuncture technique, mainly used in acute pain management, but no significant efficacy was found in adult individuals with pain, compared with the control groups. Given the poor methodological quality of the included studies, high-quality RCTs with rigorous evaluation methods are needed in the future.

Methods for Experimental Allergen Immunotherapy: Subcutaneous and Sublingual Desensitization in Mouse Models of Allergic Asthma.

Allergic asthma is characterized by airway hyperresponsiveness, remodeling, and reversible airway obstruction. This is associated with an eosinophilic inflammation of the airways, caused by inhaled allergens such as house dust mite or grass pollen. The inhaled allergens trigger a type-2 inflammatory response with the involvement of innate lymphoid cells (ILC2) and Th2 cells, resulting in high immunoglobulin E (IgE) antibody production by B cells and mucus production by airway epithelial cells. As a consequence of the IgE production, subsequent allergen reexposure results in a classic allergic response with distinct early and late phases, both resulting in bronchoconstriction and shortness of breath. Allergen-specific immunotherapy (AIT) is the only treatment that is capable of modifying the immunological process underlying allergic responses including allergic asthma. Both subcutaneous AIT (SCIT) as well as sublingual AIT (SLIT) have shown clinical efficacy in long-term suppression of the allergic response. Although AIT treatments are very successful for rhinitis, application in asthma is hampered by variable efficacy, long duration of treatment, and risk of severe side effects. A more profound understanding of the mechanisms by which AIT induces tolerance to allergens in sensitized individuals is needed to be able to improve its efficacy. Mouse models have been very valuable in preclinical research for characterizing the mechanisms of desensitization in AIT and evaluating novel approaches to improve its efficacy. Here, we present a rapid and reproducible mouse model for allergen-specific immunotherapy. In this model, mice are sensitized with two injections of allergen adsorbed to aluminum hydroxide, followed by subcutaneous injections (SCIT) or sublingual administrations (SLIT) of allergen extracts as an immunotherapy treatment. Finally, mice are challenged by intranasal allergen administrations. We will also describe the protocols as well as the most important readout parameters for the measurements of invasive lung function, serum immunoglobulin levels, isolation of bronchoalveolar lavage fluid (BALF), and preparation of cytospin slides. Moreover, we describe how to perform ex vivo restimulation of lung single-cell suspensions with allergens, flow cytometry for identification of relevant immune cell populations, and ELISAs and Luminex assays for assessment of the cytokine concentrations in BALF and lung tissue.

Is Biofeedback through an Intra-Aural Device an Effective Method to Treat Bruxism? Case Series and Initial Experience.

Biofeedback was reported as an effective concept for bruxism treatment, through increasing patient's awareness of the habit. During bruxing both ear canals become tighter, therefore, an in-ear device can provide biofeedback. The in-ear device is fitted to the ear canal in physiological status, during bruxing the ear-canal tightens resulting in stress on the canal walls and unpleasant feeling. Subsequently, patients stop their bruxing habit. The aim of this study is to provide first clinical evidence that in-ear devices have a positive impact on relieving bruxism in patients. Despite the low number of patients, this early study was designed as a controlled prospective study. The trial included seven female patients with a median age of 47.3 years (23-64 years). Only two patients implemented their devices for eight and seven months, respectively. One patient reported a relief in her symptoms, like headaches and pain intensity during the night, by 50% after three month and 80% after six months. Despite the limited number of participants, the study reflects a potential of Intra-aural devices as effective biofeedback devices in treating bruxism.

Dietary prebiotics promote intestinal Prevotella in association with a low-responding phenotype in a murine oxazolone-induced model of atopic dermatitis.

Atopic dermatitis is a chronic eczema commonly observed among children in Western countries. The gut microbiota is a significant factor in the pathogenesis, and ways to promote intestinal colonizers with anti-inflammatory capabilities are therefore favorable. The present study addressed the effects of a prebiotic, xylooligosaccharide (XOS), on the gut microbiota and ear inflammation in an oxazolone-induced dermatitis model in BALB/c mice. Mice were fed a XOS supplemented or a control diet throughout the experiment. Ear thickness and clinical skin inflammation were scored blindly after three weeks topical challenge with 0.4% oxazolone. The mice were divided into high and low responders to oxazolone-induced dermatitis based on clinical inflammation and histological evaluation of ear biopsies, and significantly fewer high responders were present in the XOS fed group. In addition, XOS fed mice had higher abundance of Prevotella spp. in their gut microbiota compared to the control fed mice. Serum IgE and ear tissue cytokine levels correlated significantly with the clinical scores, and with the abundance of Prevotella spp. The strong association between the low-responding phenotype and high abundance of Prevotella spp., indicates an alleviating effect of this intestinal colonizer in allergic sensitization. Prevotella should be considered as a relevant target for future microbiota-directed treatment strategies in atopic patients.

3α-Angeloyloxy-ent-kaur-16-en-19-oic Acid Isolated from Wedelia trilobata L. Alleviates Xylene-Induced Mouse Ear Edema and Inhibits NF-κB and MAPK Pathway in LPS-Stimulated Macrophages.

Uncontrolled inflammation is associated with many major diseases, and there is still an urgent need to develop new anti-inflammatory drugs. 3α-Angeloyloxy-ent-kaur-16-en-19-oic acid (WT-25) is an ent-kaurane dieterpenoid extracted from Wedelia trilobata, a medicinal plant with potential anti-inflammatory activity. The anti-inflammatory activity of WT-25 is better than that of its analog kaurenoic acid, but the underlying mechanism is still unknown. In this study, our aim was to study the anti-inflammatory effect of WT-25. In xylene-induced edema in mice, WT-25 produced 51% inhibition. WT-25 suppressed nitric oxide (NO) and prostaglandin E2 (PGE2) production in LPS-stimulated RAW264.7 cells by downregulating the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). WT-25 reduced expression and secretion of TNF-α and IL-6. Moreover, WT-25 inhibited NF-κB activation and its upstream signaling, decreasing phosphorylation IKK and p65 levels. WT-25 also inhibited the phosphorylation of the mitogen-activated protein kinases (MAPKs) family. Additionally, it reduced LPS-induced excessive release of reactive oxygen species (ROS) and maintained mitochondrial integrity in RAW264.7 cells. All these results indicate that WT-25 is a bioactive molecule with the potential to be developed as a novel structured anti-inflammatory drug.

In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained from Boehmeria caudata Sw. Aerial Parts.

In the context of the cancer-inflammation relationship and the use of natural products as potential antitumor and anti-inflammatory agents, the alkaloid-enriched fraction of Boehmeriacaudata (BcAEF) aerial parts was evaluated. In vitro antiproliferative studies with human tumor cell lines showed high activity at low concentrations. Further investigation on NCI-H460 cells showed an irreversible effect on cell proliferation, with cell cycle arrest at G2/M phase and programmed cell death induction. Molecular docking studies of four alkaloids identified in BcAEF with colchicine's binding site on ß-tubulin were performed, suggesting (-)-C (15R)-hydroxycryptopleurine as the main inductor of the observed mitotic death. In vivo studies showed that BcAEF was able to reduce Ehrlich tumor volume progression by 30 to 40%. Checking myeloperoxidase activity, BcAEF reduced neutrophils migration towards the tumor. The in vivo anti-inflammatory activity was evaluated by chemically induced edema models. In croton oil-induced ear edema and carrageenan (CG)-induced paw edema models, BcAEF reduced edema around 70 to 80% together with inhibition of activation and/or migration of neutrophils to the inflammatory area. All together the results presented herein show BcAEF as a potent antitumor agent combining antiproliferative and anti-inflammatory properties, which could be further explored in (pre)clinical studies.

Vestigial auriculomotor activity indicates the direction of auditory attention in humans.

Unlike dogs and cats, people do not point their ears as they focus attention on novel, salient, or task-relevant stimuli. Our species may nevertheless have retained a vestigial pinna-orienting system that has persisted as a 'neural fossil' within in the brain for about 25 million years. Consistent with this hypothesis, we demonstrate that the direction of auditory attention is reflected in sustained electrical activity of muscles within the vestigial auriculomotor system. Surface electromyograms (EMGs) were taken from muscles that either move the pinna or alter its shape. To assess reflexive, stimulus-driven attention we presented novel sounds from speakers at four different lateral locations while the participants silently read a boring text in front of them. To test voluntary, goal-directed attention we instructed participants to listen to a short story coming from one of these speakers, while ignoring a competing story from the corresponding speaker on the opposite side. In both experiments, EMG recordings showed larger activity at the ear on the side of the attended stimulus, but with slightly different patterns. Upward movement (perking) differed according to the lateral focus of attention only during voluntary orienting; rearward folding of the pinna's upper-lateral edge exhibited such differences only during reflexive orienting. The existence of a pinna-orienting system in humans, one that is experimentally accessible, offers opportunities for basic as well as applied science.

Dogs, cats, monkeys and other animals perk their ears in the direction of sounds they are interested in. Humans and their closest ape relatives, however, appear to have lost this ability. Some humans are able to wiggle their ears, suggesting that some of the brain circuits and muscles that allow automatic ear movements towards sounds are still present. This may be a 'vestigial feature', an ability that is maintained even though it no longer serves its original purpose. Now, Strauss et al. show that vestigial movements of muscles around the ear indicate the direction of sounds a person is paying attention to. In the experiments, human volunteers tried to read a boring text while surprising sounds like a traffic jam, a baby crying, or footsteps played. During this exercise, Strauss et al. recorded the electrical activity in the muscles of their ears to see if they moved in response to the direction the sound came from. In a second set of experiments, the same electrical recordings were made as participants listened to a podcast while a second podcast was playing from a different direction. The individuals' ears were also recorded using high resolution video. Both sets of experiments revealed tiny involuntary movements in muscles surrounding the ear closest to the direction of a sound the person is listening to. When the participants tried to listen to one podcast and tune out another, they also made ear 'perking' movements in the direction of their preferred podcast. The results suggest that movements of the vestigial muscles in the human ear indicate the direction of sounds a person is paying attention to. These tiny movements could be used to develop better hearing aids that sense the electrical activity in the ear muscles and amplify sounds the person is trying to focus on, while minimizing other sounds.

Free fatty acid receptor 4 (FFA4) activation ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis by increasing regulatory T cells in mice.

High dose intake of docosahexaenoic acid showed beneficial effects on atopic dermatitis in patients and was found to increase regulatory T cells in mice, but its molecular target has not been identified. Free fatty acid receptor 4 (FFA4, also known as GPR120) is a receptor sensing polyunsaturated long-chain fatty acids including docosahexaenoic acid. In the present study, we examined whether FFA4 acted as a therapeutic target of docosahexaenoic acid for treating atopic dermatitis. Experimental atopic dermatitis was induced in mice by 2,4-dinitrochlorobenzene (DNCB) sensitization on day 0, followed by repeated DNCB challenges from D7 to D48. The mice were treated with a selective agonist compound A (30 mg· kg-1· d-1, ip) from D19 to D48, and sacrificed on D49. We found that DNCB-induced atopic dermatitis-like skin lesions, i.e. hypertrophy and mast cell infiltration in skin tissues, as well as markedly elevated serum IgE levels. Administration of compound A significantly suppressed the atopic responses in ears and lymph nodes, such as hypertrophy and mast cell infiltration in the ears, enlarged sizes of lymph nodes, and elevated serum IgE and levels of cytokines IL-4, IL-13, IL-17, and IFN-γ in ear tissue. The therapeutic effects of compound A were abolished by FFA4 knockout. Similarly, increased CD4+Foxp3+ regulatory T-cell population in lymph nodes was observed in wide-type mice treated with compound A, but not seen in FFA4-deficient mice. In conclusion, we demonstrate that activation of FFA4 ameliorates atopic dermatitis by increasing CD4+Foxp3+ regulatory T cells, suggesting FFA4 as a therapeutic target for atopic dermatitis.

Comparison of hearing screening results of Syrian refugees and Turkish newborns.

OBJECTIVE: To analyze Turkish (Host) and Syrian (Refugee) newborn hearing screening results and factors of risk. METHODS: All newborns between 02.12.2017 and 31.06.2019 were screened with Automated Auditory Brainstem Response (AABR) test. A total of 874 newborns were examined (172 refugee and 702 host newborns). All screened patients were questioned in terms of consanguineous marriage, speech disorder in family, delivery method (normal vaginal birth/caesarean birth), birth weight, birth week, newborn intensive care unit (ICU) necessity, newborn icterus and phototherapy. RESULT: As for the host newborns, 360 (51.3%) passed ABR screening, 161 (23%) failed in either one ear, and 181 (25.8%) failed both ears. As for the refugee newborns, 60 (34.9%) passed ABR screening, 38 (22.1%) failed in either one ear, and 74 (43.0%) failed both ears. There was a significant statistical difference between host and refugee newborns' ears in terms of hearing loss detected in the screening test (p = 0.017). In terms of delivery method, the caesarean rate was higher in refugees, and a statistically significant difference existed between two groups (p = 0.023). There was a significant difference between refugee newborns and host newborns in terms of newborn ICU necessity rate (p = 0.014). CONCLUSIONS: It was demonstrated clearly that hearing screening test results between the two groups were affected by low socio-economic level when host and refugees newborns were compared. In line with the findings of this study, it should be taken into account that bad living conditions depending on war and immigration throughout pregnancy, delivery method, and the need for newborn ICU in the newborn period may affect hearing results in newborns significantly.

Isatis tinctoria L.-derived Petroleum Ether Extract Mediates Anti-inflammatory Effects via Inhibition of Interleukin-6, Interleukin-33 and Mast Cell Degranulation.

Isatis tinctoria L. (woad) has been used in medicine for centuries and has demonstrated anti-inflammatory effects. However, to date, no well-defined extracts with precise analysis of active substances have been developed. The aim of this study was to develop novel extracts of Isatis tinctoria L., and to characterize their active ingredients and anti-inflammatory properties. Various extracts of Isatis tinctoria L. were analysed for their active ingredients, and screened for anti-inflammatory effects using cyclooxygenase-2 activity assays. A petroleum ether extract was found to have the best effects, and was tested in a mouse model of acute allergic contact dermatitis. In the mouse model the petroleum ether extract resulted in significantly reduced ear swelling, oedema and inflammatory cell density. In mouse skin and human keratinocyte cultures, petroleum ether extract inhibited pro-inflammatory cytokine expression. Furthermore, human mast cell degranulation was significantly inhibited in LAD2 cell cultures. In conclusion, novel woad extracts were developed and shown to have anti-inflammatory properties in a contact hypersensitivity animal model and human keratinocytes. The production of such extracts and further characterization of their specific properties will enable determination of their potential dermatological effects in the treatment of inflamed and irritated skin.