Biosignatures of defective sebaceous gland activity in sebum-rich and sebum-poor skin areas in adult atopic dermatitis.

Atopic dermatitis (AD) is a composite disease presenting disruption of the skin permeability barrier (SPB) in the stratum corneum (SC). Recent evidence supports derangement of the sebaceous gland (SG) activity in the AD pathomechanisms. The objective of this study was to delineate profiles of both sebaceous and epidermal lipids and of aminoacids from SG-rich (SGR) and SG-poor (SGP) areas in AD. Both sebum and SC were sampled from SGR areas, while SC was sampled also from SGP areas in 54 adult patients with AD, consisting of 34 and 20 subjects, respectively with and without clinical involvement of face, and in 44 age and sex-matched controls. Skin biophysics were assessed in all sampling sites. Disruption of the SBP was found to be associated with dysregulated lipidome. Abundance of sapienate and lignocerate, representing, respectively, sebum and the SC type lipids, were decreased in sebum and SC from both SGR and SGP areas. Analogously, squalene was significantly diminished in AD, regardless the site. Extent of lipid derangement in SGR areas was correlated with the AD severity. The abundance of aminoacids in the SC from SGR areas was altered more than that determined in SGP areas. Several gender-related differences were found in both controls and AD subgroups. In conclusion, the SG activity was differently compromised in adult females and males with AD, in both SGR and SGP areas. In AD, alterations in the aminoacidome profiles were apparent in the SGR areas. Lipid signatures in association with aminoacidome and skin physical properties may serve the definition of phenotype clusters that associate with AD severity and gender.

Developmental iron exposure induces locomotor alterations in Drosophila: Exploring potential association with oxidative stress.

Prenatal iron (Fe) exposure has been associated with learning and cognitive impairments, which may be linked to oxidative stress resulting from elevated Fe levels and harm to the vulnerable brain. Drosophila melanogaster has contributed to our understanding of molecular mechanisms involved in neurological conditions. This study aims to explore Fe toxicity during D. melanogaster development, assessing oxidative stress and investigating behaviors in flies that are related to neurological conditions in humans. To achieve this goal, flies were exposed to Fe during the developmental period, and biochemical and behavioral analyses were conducted. The results indicated that 20 mM Fe decreased fly hatching by 50 %. At 15 mM, Fe exposure increased lipid peroxidation, and GSH levels decreased starting from 5 mM of Fe. Superoxide Dismutase activity was enhanced at 15 mM, while Glutathione S-Transferase activity was inhibited from 5 mM. Although chronic Fe exposure did not alter acetylcholinesterase (AChE) activity, flies exhibited reduced locomotion, increased grooming, and antisocial behavior from 5 mM of Fe. This research highlights potential Fe toxicity risks during development and underscores the utility of D. melanogaster in unraveling neurological disorders, emphasizing its relevance for future research.

Assessing the disparity: comparative toxicity of Copper in zebrafish larvae exposes alarming consequences of permissible concentrations in Brazil.

Copper (Cu) is a naturally occurring metal with essential micronutrient properties. However, this metal might also pose increased adverse environmental and health risks due to industrial and agricultural activities. In Brazil, the maximum allowable concentration of Cu in drinking water is 2 mg/L. Despite this standard, the impact of such concentrations on aquatic organisms remains unexplored. This study aimed to evaluate the toxicity of CuSO4 using larval zebrafish at environmentally relevant concentrations. Zebrafish (Danio rerio) larvae at 72 hr post-fertilization (hpf) were exposed to nominal CuSO4 concentrations ranging from 0.16 to 48 mg/L to determine the median lethal concentration (LC50), established at 8.4 mg/L. Subsequently, non-lethal concentrations of 0.16, 0.32, or 1.6 mg/L were selected for assessing CuSO4 -induced toxicity. Morphological parameters, including body length, yolk sac area, and swim bladder area, were adversely affected by CuSO4 exposure, particularly at 1.6 mg/L (3.31 mm ±0.1, 0.192 mm2 ±0.01, and 0.01 mm2 ±0.05, respectively). In contrast, the control group exhibited values of 3.62 mm ±0.09, 0.136 mm2 ±0.013, and 0.3 mm2 ±0.06, respectively. Behavioral assays demonstrated impairments in escape response and swimming capacity, accompanied by increased levels of reactive oxygen species (ROS) and lipid peroxidation. In addition, decreased levels of non-protein thiols and reduced cellular viability were noted. Data demonstrated that exposure to CuSO4 at similar concentrations as those permitted in Brazil for Cu adversely altered morphological, biochemical, and behavioral endpoints in zebrafish larvae. This study suggests that the permissible Cu concentrations in Brazil need to be reevaluated, given the potential enhanced adverse health risks of exposure to environmental metal contamination.

Analysis of predictive factors influencing dupilumab continuation rate in adult patients with atopic dermatitis: results from an Italian multicenter study.

OBJECTIVES: The purpose of this study was to analyze the drug survival rate of dupilumab up to 2 years in a large real-world cohort of adult patients affected by moderate/severe atopic dermatitis (AD), and to investigate the clinical, demographic and predictive factors influencing the patients' treatment persistence. MATERIAL AND METHODS: This study included adult patients affected by moderate-to-severe AD treated with dupilumab for at least 16 weeks who visited 7 dermatologic outpatient clinics in Lazio, Italy, from January 2019 until August 2021. RESULTS: A total of 659 adult patients (345 male [52.3%], mean age: 42.8 years) with an average treatment duration of 23.3 months were enrolled in the study. Overall, 88.6% and 76.1% of patients were still on treatment after 12 and 24 months, respectively. The drug survival rate for discontinuation due to AEs and dupilumab ineffectiveness was 95.0% at 12 months and 90.0% at 24 months. The main reasons for drug discontinuation included inefficacy (29.6%), failed compliance (17.4%), persistent efficacy (20.4%) and adverse events (7.8%). Adult AD onset (≥18 years) and EASI score severity measured at the last follow-up visit were the only factors significantly associated with lower drug survival. CONCLUSION: This study revealed an increased cumulative probability of dupilumab survival at 2 years, reflected by a sustained effectiveness and a favorable safety profile of the drug.

Increased Iron Levels and Oxidative Stress Mediate Age-Related Impairments in Male and Female Drosophila melanogaster.

Aging is characterized by a functional decline in the physiological functions and organic systems, causing frailty, illness, and death. Ferroptosis is an iron- (Fe-) dependent regulated cell death, which has been implicated in the pathogenesis of several disorders, such as cardiovascular and neurological diseases. The present study investigated behavioral and oxidative stress parameters over the aging of Drosophila melanogaster that, together with augmented Fe levels, indicate the occurrence of ferroptosis. Our work demonstrated that older flies (30-day-old) of both sexes presented impaired locomotion and balance when compared with younger flies (5-day-old). Older flies also produced higher reactive oxygen species (ROS) levels, decreased glutathione levels (GSH), and increased lipid peroxidation. In parallel, Fe levels were augmented in the fly's hemolymph. The GSH depletion with diethyl maleate potentiated the behavioral damage associated with age. Our data demonstrated biochemical effects that characterize the occurrence of ferroptosis over the age of D. melanogaster and reports the involvement of GSH in the age-associated damages, which could be in part attributed to the augmented levels of Fe.

Permissible concentration of mancozeb in Brazilian drinking water elicits oxidative stress and bioenergetic impairments in embryonic zebrafish.

Mancozeb (MZ) is widely used as a fungicide in Brazil due to its effectiveness in combating fungal infections in plantations. However, its toxicity to non-target organisms, including aquatic organisms, has been reported in the literature. Recently, Brazilian legislation was updated to allow a concentration of 8 µg/L of MZ in drinking water (Ordinance GM/MS nº 888, of May 4, 2021). However, the safety of this concentration for aquatic organisms has not yet been put to the test. To address this gap, we conducted a study using zebrafish (Danio rerio) embryos at 4 hpf exposed to MZ at the concentration allowed by law, as well as slightly higher sublethal concentrations (24, 72, and 180 µg/L), alongside a control group. We evaluated various morphophysiological markers of toxicity, including survival, spontaneous movements, heart rate, hatching rate, body axis distortion, total body length, total yolk sac area, and total eye area. Additionally, we measured biochemical biomarkers such as reactive oxygen species (ROS) levels, lipid peroxidation, non-protein thiols (NPSH), and mitochondrial bioenergetic parameters. Our results showed that the concentration of 8 µg/L, currently permitted in drinking water according to Brazilian legislation, increased ROS production levels and caused alterations in mitochondrial physiology. Among the markers assessed, mitochondrial bioenergetic function appeared to be the most sensitive indicator of MZ embryotoxicity, as a decrease in complex I activity was observed at concentrations of 8 and 180 µg/L. Furthermore, concentrations higher than 8 µg/L impaired morphophysiological markers. Based on these findings, we can infer that the concentration of MZ allowed in drinking water by Brazilian environmental legislation is not safe for aquatic organisms. Our study provides evidence that this fungicide is a potent embryotoxic agent, highlighting the potential risks associated with its exposure.

Family Role in Care of Patients With Neurological Conditions: International Neuroscience Nursing Research Symposium Proceedings.

ABSTRACT: BACKGROUND: Discussions during the 2022 International Neuroscience Nursing Research Symposium highlighted the impact of family in the care of neuroscience patients. This sparked conversations about the need for understanding global differences in family involvement in the care of patients with neurological conditions. METHODS: Neuroscience nurses from Germany, India, Japan, Kenya, Singapore, Saudi Arabia, the United States, and Vietnam collaborated to provide a short summary of family involvement in caring for patients with neurological conditions in their respective countries. RESULTS: Family roles for neuroscience patients vary across the globe. Caring for neuroscience patients can be challenging. Family involvement in treatment decisions and patient care can be affected by sociocultural beliefs and practices, economic factors, hospital policies, manifestation of the disease, and long-term care requirements. CONCLUSION: Understanding the geographic, cultural, and sociopolitical implications of family involvement in care is of benefit to neuroscience nurses.

Exposure to Mancozeb results in increased MAPK phosphorylation and locomotor deficits in zebrafish larvae.

Mancozeb is a widely used fungicide whose toxicity has been reported in non-target organisms, being considered to have high or very high acute toxicity to aquatic organisms. However, the toxicity of this compound is not well characterized in the developmental stages of fish. In this study, Danio rerio with 4-, 5-, and 6-days post fertilization (dpf) was exposed to MZ at non-lethal concentrations for 24, 48, or 72 h and subsequently, behavioral alterations, oxidative stress parameters and ERK, p38MAPK, and Akt phosphorylation were analyzed. MZ exposure during the larval period decreased motor performance evaluated by traveled distance, immobile time, and time spent in the peripheral area. In parallel, MZ induced ROS levels and increased the number of cells in apoptosis, causing severe DNA damage, inducing Acetylcholinesterase and Superoxide dismutase activities, and inhibiting Glutathione peroxidase and thioredoxin reductase. Additionally, phosphorylation levels of the proteins p38MAPK, ERK2, and Akt were stimulated. These findings are relevant considering the ecological implications of MZ exposure to fishes in different developmental stages and the role of the MAPK pathway in events like development and cell death.

Assessment of alcohol-induced aggressive behavior in zebrafish (Danio rerio): A practical class.

Ethanol (EtOH) is among the most consumed drugs in the world. The behavior of humans after ingestion of this drug is characteristic: At low doses it may be excitatory and at higher doses, it may induce depressant/sedative effects. Similar effects are observed in the zebrafish experimental model (Danio rerio), which has about 70% genetic similarity with humans and has been widely used in numerous research. With the objective of improving the learning of biochemistry students, this work aimed to develop a practical exercise in the laboratory for students to observe the behavioral repertoire of zebrafish under the effects of exposure to ethanol. Through this practical class, the students were able to observe the similarity of the behavior of the animal model with that of humans, showing its importance for the consolidation of knowledge, awakening in the students an interest in science and its applications in everyday life.

Cushing's Disease Presenting with Functional Neurological (Conversion) Disorder.

While psychiatric manifestations are common in patients with Cushing's syndrome (CS), to our knowledge, there are no reported cases of CS presenting with functional neurological disorder (FND), a neuropsychiatric condition in which patients experience neurological symptoms, such as motor dysfunctions, sensory symptoms, speech disorders, or nonepileptic seizures, in the absence of neurological disease. Here, we report a case of a complex patient with Cushing's disease who presented with multiple FND symptoms including nonepileptic seizures, bilateral lower extremity paralysis, decreased finger flexion resulting in limited hand function, and stuttering. This case illustrates a rare psychiatric manifestation of CS presenting as multiple neurological complaints. Furthermore, we elucidate how a multidisciplinary treatment approach improved our patient's FND symptoms.

Turnover-attachment motive of Saudi Arabia nursing workforce: A Cross-Sectional study.

AIM: This study aimed to explore the association of turnover-attachment motive with socio-demographic data among Saudi and foreign nurses in a hospital in the Eastern Province of Saudi Arabia. METHODS: A cross-sectional correlation study was conducted among n = 180 registered Saudi and foreign nurses working at a private tertiary hospital in the Eastern Province, Saudi Arabia. The turnover-attachment motive survey was used to evaluate the eight motivational forces. Data were analysed using JASP version 16 statistical software and Orange 3 version 3.26.0. The data were subjected to correlation analysis and multiple linear regression. RESULTS: Only 8% of participants were identified with a high intention to leave driven by alternative, behavioural, normative and constitutive forces. Younger healthcare workers tend to have higher intentions to quit the job; the 29-33 age group has a statistically significant negative effect, increasing intention to leave. It was found that those with 5-6 years of clinical experience at Dr. Sulaiman Al Habib Hospital, Al Khobar and no experience abroad had statistically significantly lower intention to leave. CONCLUSION: This study presented the factors influencing nursing staff to stay or leave work in a hospital in the Eastern Province of Saudi Arabia that can be a basis for reviewing existing policies and procedures to improve nurses' working conditions.

Drug survival analysis of dupilumab and cyclosporin in patients with atopic dermatitis: a multicenter study.

Purpose: This study provides a comparative survival analysis between the only two drugs approved in Italy for the treatment of moderate-to-severe AD, cyclospoorin, and dupilumab.Materials and methods: A multicenter, retrospective study, was performed to assess drug survival (DS) analysis by comparing cyclosporin (CsA) and dupilumab in 247 AD adult patients. DS was determined through Kaplan Meier survival analysis. For each patient, data regarding age, sex, medical history, and, at every visit, concomitant medications or procedures, adverse events (AEs), and Eczema Area and Severity Index (EASI) were registered.Results: At week 72, 32/247 patients (13.96%) of the dupilumab group had discontinued the drug after a mean time of treatment of 35.27 ± 11.61 weeks; therefore, the DS rate at W72 was 87.04%. The most frequent (13/32; 40.63%) reason of drug discontinuation was the achievement of complete disease remission after a mean duration of treatment of 42.28 ± 2.02 weeks. In CsA-treated patients, DS rate at W72 was 21.05% (20/95 patients). Sixty-seven out of 95 (70.53%) patients had discontinued the drug, while 8/95 (8.42%) of them were lost to follow-up during the first 12 weeks of treatment. The causes of withdrawal among the patients who stopped CsA were AEs (28/67;41.79%).Conclusions: Dupilumab has a significant longer DS when compared to CsA.

Allergic Contact Dermatitis, an Important Skin Reaction in Diabetes Device Users: A Systematic Review.

ABSTRACT: Diabetes management has undergone many advances over the years, including the introduction of devices that allow patients to monitor blood glucose and administer insulin. Although these devices have improved patients' quality of life, they are associated with adverse reactions.A systematic literature search was performed up to May 2020 in PubMed, Cochrane, and Embase databases, with no temporal restrictions. Articles were screened by title, abstract, and full text as needed. A manual search among the references of the included articles was also performed.Two hundred sixty-five articles were identified, and 50 studies met inclusion criteria. Several cases of allergic contact dermatitis due to the use of insulin infusion systems and blood glucose monitoring have been reported. Acrylates, methacrylates, and colophonium, as well as, in particular, isobornyl acrylate, represent the main allergens responsible.Skin reactions, in particular allergic contact dermatitis, are a very common adverse event caused by insulin pumps and glucose sensors, which may lead to discontinue the usage of these devices with serious consequences for the patients. Collaboration between specialists, specifically between dermatologists and diabetologists, with patients and manufacturers is essential for the correct management of diabetes devices and potential related skin reactions.

Motivação para aprender e interesse profissional de alunos do ensino médio / Motivation for learning and professional interests of students of high school

Este estudo buscou identificar o perfil motivacional e de interesse profissional dos alunos do Ensino Médio, levantar possíveis diferenças e relações entre as variáveis e ainda verificar se a motivação intrínseca pode prever a área de escolha profissional. 524 alunos da rede pública estadual de ensino de Minas Gerais e Paraná responderam a dois instrumentos: uma escala de aconselhamento profissional e uma escala de continuum motivacional. Os resultados evidenciaram uma relação entre motivação intrínseca e a área de Ciências Biológicas/da Saúde. Observou-se que a motivação intrínseca pôde prever em cerca de 10% a área de escolha profissional dos estudantes na área Ciências Biológicas/da Saúde. Os dados são discutidos à luz das implicações psicoeducacionais e do aconselhamento de carreira, visando reduzir as dificuldades para a tomada de decisão profissional dos estudantes.

This study aimed to identify the motivational and professional profile of high school students, to raise possible differences and relationships between the variables, and to verify whether the intrinsic motivation can predict the area of professional choice. The professional counseling scale and motivational continuum scale instruments were applied to 524 students from the state public school system in Minas Gerais and Paraná. The results showed a relationship between intrinsic motivation and the Biological/Health Sciences area. It was observed that the intrinsic motivation could predict in about 10% the professional choice area of the students from the Biological/Health Sciences area. The data are discussed in the light of psychoeducational implications andcareer counseling, aiming at reducing the difficulties faced by students to make their professional decisions.

Prevalence of Temporomandibular Joint Disorders in Patients with Ankylosing Spondylitis: A Cross-Sectional Study.

BACKGROUND: This study sought to investigate which temporomandibular disorders (TMD) can be expected in patients with ankylosing spondylitis (AS) and to determine the combined impact of these conditions on the psychological status, chronic pain, and functional disability. MATERIAL AND METHODS: A cross-sectional study composed of 30 patients between 18 and 65 years with ankylosing spondylitis was performed. The research protocol considered the evaluation of outcomes related to the ankylosing spondylitis (HLA-B27 antigen, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Health Assessment Questionnaire - Spondylitis (HAQ-S)) and temporomandibular disorders (axis I and II of the Research Diagnostic Criteria for Temporomandibular Disorders - RDC/TMD). Descriptive analyses were applied to express the results. RESULTS: The sample presented both AS and TMD, most of them (24) were diagnosed with conventional AS (HLA-B27 positive). The BASDAI was scored as 7.70 (2.30) (high activity of AS disease). Functional disability represented by high scores of BASFI [7.00 (2.63)] and HAQ-S [1.79 (0.62)] demonstrates the severe impact of the disease on the daily routine and quality of life. According to RDC/TMD diagnostic criteria, 17 (57%) share the three groups of TMD, and 9 (30%) share two groups of TMD (Group I and III). Over 73% of the volunteers scored high levels of chronic pain (Grade III and IV) associated with a high depression scale score. The sample scored the somatization scale (with and without pain) as severe. CONCLUSION: Patients with ankylosing spondylitis presented a high prevalence of temporomandibular disorder, most of them having the degenerative forms of TMJ disease. AS and TMD cause moderate to severe chronic pain and a negative impact on psychological status and functional capacities.

COVID-19 vaccines in adult cancer patients with solid tumours undergoing active treatment: Seropositivity and safety. A prospective observational study in Italy.

INTRODUCTION: Patients with cancer are presumed a frail group at high risk of contracting coronavirus disease (COVID-19), and vaccination represents a cornerstone in addressing the COVID-19 pandemic. However, data on COVID-19 vaccination in cancer patients are fragmentary and poor. METHODS: An observational study was conducted to evaluate the seropositivity rate and safety of a two-dose regimen of the BNT162b2 or messenger RNA-1273 vaccine in adult patients with solid cancer undergoing active anticancer treatment or whose treatment had been terminated within 6 months of the start of the study. The control group was composed of healthy volunteers. Serum samples were evaluated for SARS-COV-2 antibodies before vaccinations and 2-6 weeks after the administration of the second vaccine dose. Primary end-point: seropositivity rate. Secondary end-points: safety, factors influencing seroconversion, IgG titers of patients versus healthy volunteers, COVID-19 infection. RESULTS: Between 20th March 2021 and 12th June 2021, 293 consecutive patients with cancer-solid tumours underwent a program of COVID-19 vaccinations; of these, 2 patients refused vaccination, 13 patients did not receive the second dose of the vaccine because of cancer progression, and 21 patients had COVID-19 antibodies at baseline and were excluded. The 257 evaluable patients had a median age of 65 years (range 28-86), 66.15% with metastatic disease. Primary end-point: seropositivity rate in patients was 75.88% versus 100% in the control group. Secondary end-points: no Grade 3-4 side-effects, no COVID-19 infections were reported. Patients median IgG titer was significantly lower than in the control group; male sex and active anticancer therapy influenced negative seroconversion. BNT162b2 or messenger RNA-1273 vaccines were immunogenic in cancer patients, showing good safety profile.

CIITA gene polymorphism (rs3087456) in systemic lupus erythematosus and rheumatoid arthritis: A population-based cohort study.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are influenced by genetic variants in immune system HLA genes. The Class II Major Histocompatibility Complex Transactivator (CIITA) is an important co-activator of the HLA transcriptional complex; the single nucleotide variant (SNV) rs3087456 localized in the gene promoter region (-168 A/G) has been reported as able to modify its transcription level. In our study, we assessed CIITA rs3087456 SNV in 1,044 Brazilians from two Brazilian regions (Northeast and South) to verify the association with susceptibility and clinical manifestations of (SLE) and (RA) using TaqMan SNP Genotyping Assays System. We observed a protection for a recessive model (GG x AA+AG) for RA susceptibility and increased risk for erosion development in AG genotype patients. No significant association was observed for SLE susceptibility; however, we observed significant increased risk for Class IV and V nephritis development in G allele and GG genotype patients. In conclusion, we showed the contribution of CIITA rs3087456 to SLE or RA clinical features and RA susceptibility in the studied populations.

Emerging Skin Toxicities in Patients with Breast Cancer Treated with New Cyclin-Dependent Kinase 4/6 Inhibitors: A Systematic Review.

Three cyclin-dependent kinases 4/6, including palbociclib, ribociclib, and abemaciclib, have been approved for the treatment of patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer. The objective of this study was to evaluate the occurrence and clinical spectrum of cutaneous adverse events in patients with breast cancer following therapy with cyclin-dependent kinase 4/6 inhibitors. A systematic literature search was performed in the PubMed, Cochrane, and EMBASE databases up to November 2020 to evaluate studies published from 2015 to 2020. Articles were selected by title, abstract, and full text as required. In addition, a manual search was performed from among the references of articles included. Forty-one articles were included with a total of 13 reported dermatologic reactions including alopecia, bullous skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, radiation recall and radiation dermatitis, Henoch-Schonlein purpura, cutaneous leukocytoclastic vasculitis, subacute and chronic cutaneous lupus erythematosus, histiocytoid Sweet syndrome, vitiligo-like lesions, and erythema dyschromicum perstans. Skin toxicity is an important issue because it usually affects a patient's quality of life and could lead to a discontinuation of therapies; therefore, it is of fundamental importance to recognize and adequately manage the adverse skin reactions associated with these types of drugs.