Multidisciplinary Consideration of Potential Pathophysiologic Mechanisms of Paradoxical Erythema with Topical Brimonidine Therapy.

Rosacea is a chronic inflammatory disease with transient and non-transient redness as key characteristics. Brimonidine is a selective α2-adrenergic receptor (AR) agonist approved for persistent facial erythema of rosacea based on significant efficacy and good safety data. The majority of patients treated with brimonidine report a benefit; however, there have been sporadic reports of worsening erythema after the initial response. A group of dermatologists, receptor physiology, and neuroimmunology scientists met to explore potential mechanisms contributing to side effects as well as differences in efficacy. We propose the following could contribute to erythema after application: (1) local inflammation and perivascular inflammatory cells with abnormally functioning ARs may lead to vasodilatation; (2) abnormal saturation and cells expressing different AR subtypes with varying ligand affinity; (3) barrier dysfunction and increased skin concentrations of brimonidine with increased actions at endothelial and presynaptic receptors, resulting in increased vasodilation; and (4) genetic predisposition and receptor polymorphism(s) leading to different smooth muscle responses. Approximately 80% of patients treated with brimonidine experience a significant improvement without erythema worsening as an adverse event. Attention to optimizing skin barrier function, setting patient expectations, and strategies to minimize potential problems may possibly reduce further the number of patients who experience side effects.FundingGalderma International S.A.S., Paris, France

Music in noise recognition: An EEG study of listening effort in cochlear implant users and normal hearing controls

Despite the plethora of studies investigating listening effort and the amount of research concerning music perception by cochlear implant (CI) users, the investigation of the influence of background noise on music processing has never been performed. Given the typical speech in noise recognition task for the listening effort assessment, the aim of the present study was to investigate the listening effort during an emotional categorization task on musical pieces with different levels of background noise. The listening effort was investigated, in addition to participants’ ratings and performances, using EEG features known to be involved in such phenomenon, that is alpha activity in parietal areas and in the left inferior frontal gyrus (IFG), that includes the Broca’s area. Results showed that CI users performed worse than normal hearing (NH) controls in the recognition of the emotional content of the stimuli. Furthermore, when considering the alpha activity corresponding to the listening to signal to noise ratio (SNR) 5 and SNR10 conditions subtracted of the activity while listening to the Quiet condition—ideally removing the emotional content of the music and isolating the difficulty level due to the SNRs- CI users reported higher levels of activity in the parietal alpha and in the homologous of the left IFG in the right hemisphere (F8 EEG channel), in comparison to NH. Finally, a novel suggestion of a particular sensitivity of F8 for SNR-related listening effort in music was provided

WEUSEDTO—Water End USE Dataset and TOols: An open water end use consumption dataset and data analytics tools

Globalization, climate changes, innovative technologies and new human habits have increased atten- tion to water conservation and management. Therefore, behavioural studies became a key element to understand how and when water is used in residential environment. Water End USE Dataset and TOols (WEUSEDTO), an open water end use consumption dataset and data analytics tools, has been released to help researchers, water utilities and companies to test models and algorithms on real water consumption data. The dataset combines with some notebook python able to analyse high-resolution water data (data recorded with 1 sample per second) to provide several tools to manage raw data, compute statistical analysis, learn fixture usage and generate synthetic simulation models. In addition, washbasin flow data were used as a test case to illustrate the main features of WEUSEDTO: providing volume and duration of single events, classifying usages and simulating user’s behaviour

Seborrheic Dermatitis: Exploring the Complex Interplay with Malassezia.

Seborrheic dermatitis (SD) is a chronic inflammatory skin condition often involving the sebaceous-rich areas, characterized by erythematous scaly lesions. It is frequently observed in individuals with immune dysregulation, suggesting the interplay between the immune system and disease development. An altered immune environment leads to an exaggerated inflammatory response with the activation of innate immunity, involving the participation of mast cells, γδ T cells, and the NOD-LRR-pyrin-domain-containing protein 3 (NLRP3) inflammasome. This review aims to assess the complex relationship between Malassezia and the immune system in the pathogenesis of SD. We will explore how an impaired immune response predisposes the skin to Malassezia overgrowth and infection. We will examine the role of adaptive immunity, particularly T helper cells, in driving chronic inflammation in SD. All actors involved, whether part of innate or adaptive immunity, are responsible for the release of pro-inflammatory cytokines, which contribute to the progression of the disease. Therapeutic strategies aimed at the modulation of the immune response in SD have been tested in clinical trials evaluating the efficacy of immunomodulatory treatments in the management of SD. This review synthesizes insights from immunological studies and clinical trials to present an in-depth analysis of the immune mechanisms underpinning SD, thereby proposing targeted therapeutic strategies for its management

Criteria, objectives and methodologies for water network partitioning

Water distribution networks are complex infrastructures characterized by very large dimensions (meshed networks with thousands of nodes) and reduced accessibility (generally they are buried underground). These peculiarities make it particularly difficult to manage and show numerous criticalities; at the same time, water distribution networks represent one of the main subsystems of smart cities. The paradigm “divide et impera” is a valid technique to improve the management and facilitate the maintenance, the water balance estimation, the water leakage detection and the pressures control. On this side, Water network District Metering (WDM), a method developed in England, and already implemented in many countries, represents a modern technique to organize urban water systems, offering new perspectives for design, management and maintenance. The WDM is recommended as one of the best practice to limit the huge amount of dispersed water in urban networks, simplifying water leakage detection, carrying out pressure management, improving water system management and monitoring of district hydraulic data. On this subject, the authors developed a specific software (SWANP 3.0) for water network partitioning that integrates the main optimization algorithms. This paper shows the main aspects of water network partitioning summarizing the principal recently proposed techniques in the literature aimed to find the best partitioning layout from an economic and performance point of view

The Effectiveness of Targeted Electrical Stimulation via Cochlear Implant on Tinnitus-Perceived Loudness

Introduction: The cause of tinnitus improvement in cochlear implant (CI) users is not understood. On the basis that a spatially limited dysfunction in the auditory pathway could cause tinnitus, we used single-channel stimulation to evaluate any variation of tinnitus-perceived loudness and identify the cochlear regions involved. Materials and Methods: It was an observational prospective case-crossover study. After the first mapping, 21 adults with unilateral CI and chronic tinnitus expressed their tinnitus loudness based on the Visual Analog Scale (VAS) score (0–10) at baseline (L0), during a 10 s single-channel stimulation with C-level of electric current (L1) and 30 min after CI activation (L2). Tinnitus reduction [RT = (L0 – L1) × 100/L0] > 50% was considered significant. VAS outcomes were compared between baseline (L0) and (each) single-channel stimulation (L1) to find the channel with the greatest RT (suppressive channel-SC), whose frequency range revealed the cochlear region involved. Seven patients with asymmetric hearing loss underwent the pitch-matching test to identify the actual frequency evoked by the SC. We compared selective (L1) and non-selective (L2) intracochlear stimulation using paired t-test. Preoperative Tinnitus Handicap Inventory (THI) score was compared with those at 1, 6, and 12 months with paired t-tests to evaluate long-term tinnitus perception. Results: We observed a significant reduction of tinnitus loudness during the experimental procedure [L0 (6.4 ± 2.4) vs. L1 (1.7 ± 2.7), p = 0.003]. A total of 15/21 patients (71.4%) had a significant (RT > 50%) and selective improvement, reporting a mean L1 of 0.4 ± 2.0 (p = 0.0001). In 10/15 (66.6%) patients, the SC was in the apical turn, within 1,000 Hz; in 5/15 patients (33.4%) within 4,000 Hz. The cochlear region 125–313 Hz was the most affected by tinnitus improvement (p = 0.0074). Targeted stimulation was more effective than non-selective stimulation [L1 vs. L2 (4.3 ± 2.5), p = 0.0022]. In 3/7 patients, the perceived pitch did not fall within the SC frequency ranges. All patients with selective attenuation described tinnitus as monotone. Patients with non-selective attenuation had polyphonic tinnitus and better THI results after 1 year. Conclusion: Targeted intracochlear electrical stimulation improved chronic tinnitus perception, especially in monotone tinnitus, and the apical region was mainly involved. Our results provide new insights into the pathophysiological mechanisms of tinnitus and targets for innovative therapeutic strategies

GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease—study protocol and preliminary results

Background: GENetics of mOyaMoyA (GEN-O-MA) project is a multicenter observational study implemented in Italy aimed at creating a network of centers involved in moyamoya angiopathy (MA) care and research and at collecting a large series and bio-repository of MA patients, finally aimed at describing the disease phenotype and clinical course as well as at identifying biological or cellular markers for disease progression. The present paper resumes the most important study methodological issues and preliminary results. Methods: Nineteen centers are participating to the study. Patients with both bilateral and unilateral radiologically defined MA are included in the study. For each patient, detailed demographic and clinical as well as neuroimaging data are being collected. When available, biological samples (blood, DNA, CSF, middle cerebral artery samples) are being also collected for biological and cellular studies. Results: Ninety-eight patients (age of onset mean ± SD 35.5 ± 19.6 years; 68.4% females) have been collected so far. 65.3% of patients presented ischemic (50%) and haemorrhagic (15.3%) stroke. A higher female predominance concomitantly with a similar age of onset and clinical features to what was reported in previous studies on Western patients has been confirmed. Conclusion: An accurate and detailed clinical and neuroimaging classification represents the best strategy to provide the characterization of the disease phenotype and clinical course. The collection of a large number of biological samples will permit the identification of biological markers and genetic factors associated with the disease susceptibility in Italy

Celiac crisis as the life-threatening onset of celiac disease in children. a case report

Celiac disease (CD) is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. In rare cases, CD may occur with a severe potential life-threatening manifestation known as a celiac crisis (CC). This may be a consequence of a delayed diagnosis and expose patients to possible fatal complications. We report the case of a 22-month-old child admitted to our hospital for a CC characterized by weight loss, vomiting, and diarrhea associated with a malnutrition state. Early identification of symptoms of CC is essential to provide a prompt diagnosis and management