Tumor-derived exosomes are crucial for early non-invasive and accurate tumor diagnosis in clinical. The development of highly sensitive, simple and intuitive exosome assays has sparked a research upsurge in clinical diagnostics. Here, we develop a bio-responsive the intelligent DNA hydrogel loaded with CRISPR/Cas12a for universal and ultrasensitive detection of the exosomes. The aptamer serves as the target response unit and switch of the intelligent DNA hydrogel network. The target competitively disintegrates the region of the DNA linkers then Cas12a/crRNA encapsulated in the intelligent DNA hydrogel can be released and activated by the collateral sequence, resulting in a high fluorescent intensity for exosome detection at the detection limit of 119 particles/μL. Moreover, a prefabricated colorimetric tube is made by loading a colorimetric filter membrane on the tube lid and intelligent DNA hydrogel on the tube bottom, which enables one-pot portable colorimetric detection. Without the need for laboratory instruments and professionals, this strategy allows for naked eye detection with LOD as low as 104 particles/μL, and shows great applicability in distinguishing between healthy individuals, pretreatment patients, and post treatment patients after obtaining a testable analyte. Collectively, this study constructs an ultra-sensitive detection platform for exosomes, which enables one-step sensing and dual signal output, making it a promising tool for the application of liquid biopsy based on exosomes in clinical diagnosis.

Objective To evaluate the immune effect of the COVID-19 vaccination in patients with coronary artery disease. Methods One hundred and fifty patients were randomly selected among patients with coronary heart disease, including 100 in the vaccination group and 50 in the control group. A retrospective cohort study was conducted to investigate the infection rate of the two groups of people infected with the SARS-CoV-2 during its outbreak and the occurrence of related symptoms after infection. Results The infection rate of the inoculated group and the control group was 91% and 62%, respectively，and the difference was statistically significant（X 2=4.854，P＜0.05）. The incidence of myalgia was 62.6% and 41.9%, respectively，and the difference was statistically significant（X 2=4.052，P＜0.05）. The probability of nasal congestion and rhinorrhea was 46.2% and 22.6%, respectively，and the difference was statistically significant（X 2=5.347，P＜0.05）. Conclusion On patients with coronary heart disease, the COVID-19 vaccine had a relatively poor immunological response.

Objectives: This study aimed to compare patient perspectives and experiences between per-meatal and post-aural tympanoplasty techniques, focusing on scar perception, postoperative symptoms, return to work, and quality of life (QOL). Design: Retrospective comparative study. Setting: Secondary care hospital. Participants: Fifty-four patients who underwent tympanoplasty via either per-meatal or post-aural methods. Main Outcome Measures: Patient-reported scar perception, postoperative symptoms and quality of life reported using validated patient reported outcome measure- The Chronic Otitis Media Benefit Inventory (COMBI) score, patient reported return time off work. Results: Scar perception was favourable in both groups. Most patients in the post-aural group (96%) were content with their scar, while 83% of the per-meatal group patients were not bothered by the possibility of a scar behind the ear. Long term postoperative symptoms, return to work, and quality of life (QOL) measures were comparable between the two groups. The Chronic Otitis Media Benefit Inventory (COMBI) scores showed no statistically significant difference between the two surgical techniques. Conclusion: Patient experiences and outcomes were similar between per-meatal and post-aural tympanoplasty techniques. Clinicians should consider individual patient factors and expectations when choosing a surgical approach.

Background: Transthoracic echocardiography (TTE) plays a key role in the initial work-up of myocarditis where the identification of pathologic structural and functional changes may assist in its diagnosis and management. The aim of this systematic review was to appraise the evidence for the utility of echocardiographic parameters of cardiac structure and function in the diagnosis of acute myocarditis in the adult population. Methods: A systematic literature search of medical databases was performed using PRISMA principles to identify all relevant studies assessing TTE parameters in adult patients with myocarditis (1995-2020; English only; PROSPERO registration CRD42021243598). Data for a range of structural and functional TTE parameters were individually extracted and those with low heterogeneity were then meta-analysed using a random-effects model for overall effect size, and assessed through standardized mean difference (SMD). Results: Available data from up to six included studies revealed that myocarditis can be reliably differentiated from healthy controls using echocardiographic measures of left ventricular (LV) size and systolic function, in particular LV end-diastolic diameter, LV ejection fraction (LVEF) and LV global longitudinal strain (LV-GLS) (p≤0.01 for all). LV-GLS demonstrated the highest overall effect size, followed by LVEF and LVEDD (SMD: |0.46-1.98|). Two studies also demonstrated that impairment in LV-GLS was associated with adverse cardiovascular outcomes in this population, irrespective of LVEF. Conclusions: LV-GLS demonstrated the greatest overall effect size and therefore ability to differentiate myocarditis populations from healthy controls. GLS was also shown to be a predictor of adverse cardiovascular outcomes, in this population.

IntroductionBipolar disorder is a chronic and severe mental health condition characterized by recurring episodes of mania and depression. It affects approximately 1-2% of the global population, and its impact extends beyond the individual diagnosed to significantly influence their close relationships and family dynamics (American Psychiatric Association, 2013; Merikangas et al., 2011). The unpredictable and intense mood swings associated with bipolar disorder can challenge the emotional stability and communication patterns within relationships, leading to distress and disruptions in family life.1.1 Understanding Bipolar Disorder and its ManifestationsBipolar disorder encompasses two main mood episodes: the manic phase, characterized by elevated and expansive moods, excessive energy, and impulsive behaviors, and the depressive phase, marked by feelings of sadness, hopelessness, and loss of interest in activities (American Psychiatric Association, 2013). These mood shifts can be distressing and confusing for both the individual with bipolar disorder and their loved ones.1.2 The Impact of Bipolar Disorder on RelationshipsThe fluctuating nature of bipolar disorder poses unique challenges to relationships. During manic episodes, individuals may engage in risky behaviors, experience heightened irritability, and have difficulty focusing on others’ needs (Yatham et al., 2018). In contrast, depressive episodes can lead to withdrawal, emotional numbing, and reduced engagement with partners and family members (Miklowitz & Johnson, 2009). The interplay between these mood swings and relationship dynamics can result in conflicts, emotional distancing, and strained communication patterns.1.3 Effect on Family DynamicsBipolar disorder’s impact extends to the entire family unit, affecting not only intimate partners but also children, parents, and siblings. Family members may experience feelings of helplessness, confusion, and frustration as they attempt to support their loved one while navigating the challenges posed by the disorder (Magaña et al., 2015). The increased stress within the family system can lead to changes in roles, communication breakdowns, and potential disruptions in daily routines.1.4 Importance of Addressing the Impact on Relationships and FamilyRecognizing and understanding the impact of bipolar disorder on relationships and family dynamics is essential for providing comprehensive care and support. By addressing these challenges, mental health professionals can tailor interventions to promote healthier coping strategies and enhance relationship resilience. Furthermore, fostering open communication and providing support systems can help partners and family members manage the emotional toll of supporting a loved one with bipolar disorder.In conclusion, bipolar disorder significantly influences relationships and family life, affecting emotional dynamics, communication patterns, and family functioning. By understanding the manifestations of bipolar disorder within relationships, mental health professionals can develop targeted interventions to alleviate distress and promote healthy coping strategies for both individuals with bipolar disorder and their families.

IntroductionArt therapy is an innovative and versatile form of psychotherapy that utilizes the creative process of art-making as a therapeutic tool to address emotional, psychological, and social challenges. This approach acknowledges the inherent connection between art and human expression, dating back to ancient times when art was used for healing and self-discovery (Malchiodi, 2012). Over the years, art therapy has evolved into a distinct therapeutic practice, combining elements of psychology, art, and counseling to empower individuals to explore their inner world through artistic expression.The use of art in healing dates back to ancient civilizations, such as the Greeks, Egyptians, and Native Americans, who recognized the therapeutic potential of creative expression (Carr, 2004). However, it was not until the 20th century that art therapy emerged as a formal discipline, with pioneers like Margaret Naumburg and Edith Kramer paving the way for its integration into the field of psychology (Rubin, 2016).Art therapy is grounded in various theoretical frameworks, including psychodynamic, humanistic, and cognitive-behavioral approaches (Malchiodi, 2012). These theories provide the foundation for understanding the underlying mechanisms through which art-making can promote emotional healing and self-awareness. The integration of these diverse theoretical perspectives makes art therapy a flexible and adaptable modality, capable of addressing a wide range of mental health issues and population groups.In recent years, the efficacy of art therapy has been supported by a growing body of research that examines its therapeutic outcomes and mechanisms. Studies have demonstrated its positive impact on reducing anxiety, depression, and stress while enhancing overall well-being and quality of life (Kaimal et al., 2017; Luzzatto, 2021). Additionally, neuroscientific research has shed light on the brain mechanisms activated during art-making, offering insights into how creativity influences emotional regulation and cognitive processes (Schore, 2019).Despite these advances, some aspects of art therapy’s efficacy and underlying mechanisms remain underexplored. This article aims to bridge this gap by exploring the multifaceted nature of art therapy and the mechanisms through which it facilitates therapeutic change. By delving into historical foundations, theoretical perspectives, and emerging research findings, this article seeks to provide a comprehensive understanding of the therapeutic power of art and its significance in contemporary mental health practice.

IntroductionAnxiety and sleep disturbances are prevalent and interconnected issues that significantly impact individuals’ mental health and overall well-being. Anxiety disorders, characterized by excessive worry, fear, and heightened arousal, affect approximately 284 million people worldwide (World Health Organization, 2017). Concurrently, sleep problems are a global concern, affecting nearly one-third of the adult population (Ohayon, 2012). Mounting evidence suggests a bidirectional relationship between anxiety and sleep, wherein anxiety can disrupt sleep patterns, and poor sleep can exacerbate anxiety symptoms.The interplay between anxiety and sleep is not merely coincidental; instead, it stems from shared neurobiological mechanisms. The amygdala, a key brain structure involved in processing emotions and threat perception, plays a pivotal role in both anxiety and sleep regulation (McEwen et al., 2015). Additionally, the hypothalamic-pituitary-adrenal (HPA) axis, responsible for the stress response, influences both anxiety and sleep-wake cycles (Sapolsky, 2003).On one hand, anxiety can disrupt sleep through various mechanisms. Individuals with anxiety often experience heightened cognitive and physiological arousal, leading to difficulties falling and staying asleep (Riemann et al., 2010). Sleep disturbances in anxiety can manifest as insomnia, characterized by difficulties initiating or maintaining sleep, and frequent nocturnal awakenings (American Psychiatric Association, 2013). Furthermore, anxiety-related nightmares can disrupt sleep continuity and contribute to sleep-related distress (Levin & Fireman, 2002).On the other hand, sleep disturbances can fuel anxiety symptoms. Sleep deprivation can lead to heightened emotional reactivity and impaired cognitive functions, amplifying anxiety-related thoughts and emotions (Yoo et al., 2007). Sleep fragmentation, characterized by frequent awakenings during the night, can impair emotional regulation processes, making it challenging for individuals to manage anxiety (Choi et al., 2008). Moreover, sleep disturbances can contribute to cognitive biases, such as negative attentional biases, further exacerbating anxiety-related cognitions (Bradley et al., 1997).Understanding the bidirectional relationship between anxiety and sleep is crucial, as it has significant implications for clinical practice and public health. Identifying the underlying neurobiological mechanisms and risk factors associated with this relationship can inform targeted interventions for individuals experiencing anxiety-related sleep disturbances. Moreover, addressing both anxiety and sleep disturbances concurrently may lead to more effective treatment outcomes and improved quality of life for affected individuals.The current article aims to provide a comprehensive review of the bidirectional relationship between anxiety and sleep. It explores the neurobiological mechanisms linking anxiety and sleep, examines the impact of anxiety on sleep and vice versa, and identifies vulnerable populations at higher risk for experiencing this bidirectional relationship. Additionally, the article discusses evidence-based strategies for improving sleep in individuals with anxiety and emphasizes the importance of integrating sleep interventions within anxiety treatment protocols. By shedding light on this complex relationship, this article seeks to contribute to the development of targeted interventions that promote improved mental health and sleep quality in individuals struggling with anxiety-related sleep disturbances.

IntroductionAcceptance and Commitment Therapy (ACT) has emerged as a prominent and evidence-based psychotherapeutic approach, attracting significant attention from researchers, practitioners, and clients alike. Developed by Steven C. Hayes in the 1980s, ACT is rooted in the theoretical framework of Relational Frame Theory (RFT) (Hayes, Barnes-Holmes, & Roche, 2001), which emphasizes the role of language and cognition in human behavior and emotional experience.The primary goal of ACT is to promote psychological flexibility, a key construct that refers to the ability to be present in the moment, adapt to situational demands, and persist in behaviors that align with one’s values, even in the presence of difficult or distressing thoughts and emotions (Kashdan & Rottenberg, 2010). Psychological flexibility has been linked to greater overall well-being, improved mental health outcomes, and increased life satisfaction (Kashdan & Breen, 2007).At its core, ACT is built on six interconnected processes that facilitate psychological flexibility (Hayes et al., 2006). This article provides a comprehensive exploration of the foundational principles, key processes, and treatment components that form the basis of ACT. By delving into the theoretical underpinnings of RFT and highlighting the significance of psychological flexibility, this paper aims to illuminate the essential elements of ACT that contribute to its efficacy as a therapeutic intervention.

MEASLES - AN ENT DIAGNOSIS?

Dear Editor,We read the article by Salimi et al. on the endovascular management of post PCNL vascular injuries with great interest 1. In their study, the authors successfully diagnosed and treated post Percutaneous nephrolithotomy (PCNL) hematuria in 14 patients using angiography and subsequent embolization. They reported a 100% success rate, with ten patients having pseudoaneurysm (PA), four having arteriovenous fistula (AVF), and one having both subscapular hematoma and PA 1. The authors concluded that angiography is a safe and effective method for diagnosing etiology and treating post-PCNL hemorrhage.While we acknowledge the significance of the interventions and outcomes presented in this article, we believe further clarification on certain aspects is necessary. Firstly, it is crucial to understand the criteria used to determine the necessity of an invasive procedure such as angiography and coil embolization. The authors did not specify the threshold for significant hematuria that prompted the invasive intervention. Factors such as the number of units of packed red blood cells transfused, the presence of shock, or the duration of gross hematuria following the index PCNL procedure should be elucidated to provide a clearer context for their approach.Additionally, the authors attributed gross hematuria to PA or AVF in all cases. However, it is important to acknowledge that post-PCNL hematuria can have other causes and treatments, including infection, as reported by Dhangar and colleagues 2. Even in cases with vascular etiologies such as PA, other non-invasive alternatives, such as administration of tranexamic acid, have been reported by Kumar et al.3 and Feng et al. 4 as effective solutions.Considering the diversity in etiology and management options for post-PCNL hematuria, we propose that utilizing non-invasive investigations, such as computerized tomography (CT) angiogram, before proceeding to angiography, an invasive procedure, would be a reasonable approach. This could help in better patient selection for invasive procedures, potentially reducing the risk and cost associated with unnecessary interventions. This point would be clearer with a larger patient cohort.In conclusion, despite the benefits and precision of angiography, we suggest that it might be better for physicians to consider non-invasive utilities like CT angiograms as the first step of evaluation and also have a risk assessment for ordering invasive investigation until clear clinical and laboratory data indicate post-PCNL vascular injury needs angioembolization.

Even though drinking water utilities are not meant to fight wildfires, they quickly become stakeholders, if not first responders, when their resources are needed for firefighting. The August 2023 wildfires on the island of Maui, Hawaii, USA, have highlighted weaknesses at this intersection. We analyze this extreme case to support disaster-response lessons for water utilities and to guide further research and policy. First, emergency water releases were not available in a timely manner. Second, fire and wind toppled power lines, causing power outages that inhibited pumping water. Third, many structures were a total loss despite water doused on them, consuming valuable water. Finally, water was lost through damaged premise plumbing in burned structures, further reducing system pressure. These conditions emphasize that water utilities need to access emergency water supplies quickly, establish reliable backup electricity, coordinate with firefighters on priority water uses, and shut valves in burned areas to preserve water. While further research will certainly follow, we present these early lessons as starting points.

Individuals with hoarding disorder (HD) have difficulty parting with personal possessions, which leads to the accumulation of excessive clutter. According to a proposed biphasic neurobiological model, HD is characterized by blunted central and peripheral nervous system activity at rest and during neutral (non-discarding) decisions, and exaggerated activity during decision-making about discarding personal possessions. Here, we compared the error-related negativity (ERN) and psychophysiological responses (skin conductance, heart rate and heart rate variability, and end tidal CO2) during neutral and discarding-related decisions in 26 individuals with HD, 37 control participants with anxiety disorders, and 28 healthy control participants without psychiatric diagnoses. We also compared alpha asymmetry between the HD and control groups during a baseline resting phase. Participants completed a series of Go/No Go decision-making tasks, one involving choosing certain shapes (neutral task) and the other involving choosing images of newspapers to imaginally “discard” (discarding task). Contrary to hypotheses, there were no group differences in the ERN or any psychophysiological measures. Alpha asymmetry at rest did not differ between groups. The findings suggest that the ERN and psychophysiological responses may not differ in individuals with HD during simulated discarding decisions relative to control participants, although the null results may be explained by methodological challenges in using Go/No Go tasks as discarding tasks. Future replication and extension of these results will be needed using ecologically valid discarding tasks.

Regular exercise is known to positively impact neurocognitive health, particularly in aging individuals. However, low adherence, particularly among older adults, hinders the adoption of exercise routines. While neuroplasticity mechanisms largely support the cognitive benefits of exercise, the link between physiological and behavioral factors influencing exercise adherence remains unclear. This study aimed to explore this association in sedentary middle-aged and older adults. Thirty-one participants underwent an evaluation of neuroplasticity using transcranial magnetic stimulation (TMS) to measure changes in motor-evoked potentials following intermittent theta-burst stimulation (iTBS). Health history, cardiorespiratory fitness, and exercise-related behavioral factors were also assessed. The participants engaged in a 2-month supervised aerobic exercise program, attending sessions three times a week for 60 minutes each, totaling 24 sessions at a moderate-to-vigorous intensity. They were divided into Completers (n=19), who attended all sessions, and Dropouts (n=12), who withdrew early. Completers exhibited lower smoking rates, exercise barriers, and resting heart rates compared to Dropouts. For Completers, regression models revealed that post-iTBS changes (β= -7.78, p= .013) and self-efficacy (β= −.51, p= .019) predicted exercise adherence (adjusted-R2= 0.44). Larger post-iTBS increases in motor-evoked potential amplitude indicated greater effectiveness of cortico-motor plasticity and were associated with better exercise adherence. In conclusion, this study highlights the significance of cortico-motor plasticity, self-efficacy, and cardiovascular health in exercise adherence. Given the well-established cognitive benefits of exercise, addressing sedentary behavior and enhancing self-efficacy are crucial for promoting adherence and optimizing brain health. Clinicians and researchers should prioritize assessing these variables to improve the effectiveness of exercise programs.

Aims: This study aimed to investigate the potential impact of tacrolimus (TAC) exposure on clinical outcomes after lung transplantation. Methods: This retrospective observational study enrolled a total of 234 lung transplant recipients. TAC trough levels (C0) were collected for 3 intervals: 0–3 months, 3–12 months, and 12–24 months. The intra-patient variability (IPV) was calculated using coefficient of variation. Genotyping of CYP3A5*3 (rs776746) was performed. Patients were further divided into groups based on the C0 cut-off value of 8 ng/mL and IPV cut-off value of 30%. Cox proportional hazards regression models were used to explore the potential impact of C0 and IPV on outcomes of interests, including donor-specific antibodies (DSA), chronic lung allograft dysfunction (CLAD) and mortality. Results: The influence of CYP3A5*3 polymorphism was only significant for C0 and IPV during the first 3 months. Low C0 (< 8 ng/mL) at 3–12 months increased the risk of DSA (hazard ratio [HR] 2.820, 95% confidence interval [CI] 1.093–7.276) and mortality (HR 2.220, 95% CI 1.162–4.243), while High IPV (>=30%) during this period was associated with an increased risk of mortality (HR 2.100, 95% CI 1.120–3.937). Patients with Low C0/High IPV combination had significantly higher risks for DSA (HR 4.534, 95% CI 1.326–15.507) and survival (HR 4.205, 95% CI 1.739–10.168), surpassing the predictive power provided by C0 or IPV alone. Conclusion: A combination of Low C0/High IPV might be considered in categorizing patients towards risk of adverse clinical outcomes following lung transplantation.

We describe two cases of idiopathic VT arising from the postero-septal RVOT in both cases. Each case demonstrates an important learning point and advantage of multi-spline multi-electrode mapping catheters in idiopathic outflow VT. In the first case two dominant PVC morphologies can be clearly seen which we believe originate from a single site of origin with multiple exit sites caused by focal fibrosis. In the second case, focal fibrosis in this region leads to anisotropic conduction of the RVOT in areas of low voltage. We surmise that multi-spline multi-electrode catheters are essential in such cases as extensive point-by-point mapping could significantly prolong procedure time and fail to identify the earliest activation site in the case of anisotropic tissue conduction due to variations in activation latency.

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia that affects millions of people worldwide. We aim to investigate how to improve prognostic value of recurrence for atrial fibrillation patients after cryoablation by non-linear survival models. Methods: In this study, we retrospectively reviewed data from 1023 patients who underwent cryoablation surgery for AF at Fujian Provincial Hospital (FPH). We generated radiomics signatures (RSI) and a clinical signature (CLI) using a non-linear survival model by repeated 10-fold cross-validation. The comprehensive risk score (TCRS) was obtained by linearly weighting the multivariate Cox proportional risk model. Results: The combination of RSI and CLI indicators had a significantly higher area under the curve (AUC) in the ROC curve of the training set (AUC=0.955) compared to the AUC of a single indicator CLI (AUC=0.862). The TCRS showed better prognostic performance compared to the traditional Lasso-Cox models, with AUC of 0.955 vs 0.664. The accuracy of the model was further confirmed by the C-indices of RSI (C-index: 0.8894; 95%CI: 0.8166-0.9621), CLI (C-index: 0.8431; 95%CI: 0.7466-0.9395), and TCRS (C-index: 0.9072; 95%CI: 0.8281-0.9864) in validation set 2. Conclusions: Under a nonlinear survival model, TCRS which combines RSI and CLI indicators has potential as a promising prognostic tool for post-cryoablation AF patients.

A document by Meltem Ozturan. Click on the document to view its contents.

Laminitis associated with hyperinsulinemia a significant cause of morbidity and mortality in horses with equine metabolic syndrome. The diagnosis and management of insulin dysregulation are therefore critical to prevent the development of hyperinsulinemia-associated laminitis. This review article aims to help primary care clinicians manage patients with insulin dysregulation by providing an overview of diagnostics, management strategies and new therapies that are available.

A document by Faisal Nabi. Click on the document to view its contents.

Large acute epidural hematoma from head pin fixation fractureAuthorsVinicius Trindade Gomes da Silva1 – viniciustrindade@hotmail.comLouise Makarem1 - louisemakarem@gmail.comRhuann Pontes dos Santos Silva² - rhuannpontes02@gmail.comManoel Jacobsen Teixeira1 – manoeljacobsen@gmail.comWellingson Silva Paiva1 - wellingsonpaiva@yahoo.com.brInstitutions1 Division of Neurosurgery at University of São Paulo.² Catholic University of Pernambuco, Recife, Brazil.PAIVA et al: EPIDURAL HEMATOMA FROM HEAD PIN FIXATION

Gentamicin (GM) is an aminoglycoside antibiotic with a rapid bactericidal effect in the treatment of many infections. However, its use in high concentrations for more than 7 days causes nephrotoxic side effects. It was aimed to determine the biochemical and molecular activities of resatorvid and alpha lipoic acid (ALA) on GM induced nephrotoxicity in rats. In the study, 34 Wistar albino rats were randomly distributed; Healthy control (n:6), Gentamicin (80 mg/kg, n:7), Gentamicin+Sham (%10 hydroalcoholic solution, n:7), Gentamicin+resatorvid (5 mg/kg, n:7), Gentamicin+ALA (100 mg/kg, n:7). Urinary IL-18, KIM-1 and NGAL levels were statistically decreased by resatorvid treatment, and KIM-1 levels were statistically decreased by ALA treatment compared to the gentamicin group. In addition, urine creatinine was partially decreased by resatorvid and ALA. NRF-2, CAS-3 and NR4A2 expressions were statistically decreased by resatorvid and ALA treatment. Nevertheless, NF-κB was statistically decreased only with resatorvid. The nephrotoxicity that limits the use of gentamicin in infections can reduce by resatorvid in the future. Therefore, it can be used for a longer and more effective in infections.

Background: Atopic dermatitis (AD) is a chronic skin condition impacting quality of life. Allergen recognition via specific IgE triggers immune responses and allergy symptoms. Cross-reactivity may induce auto-IgE responses and worsen AD. We aimed to analyze molecular mimicry between human AQP3 and Aspergillus fumigatus aquaporin, a potential allergen source. Methods: In silico analysis compared human (AQP3) and A. fumigatus aquaporin sequences with 25 aquaporins from allergenic sources. Sequences were obtained from UniProt and NCBI. Phylogenetic relationships and homology-based modeling were performed, with ElliPro predicting conserved antigenic regions on 3D structures. Results: Global identity among aquaporins was 32.6%, but one antigenic site exhibited 71.4% local conservation. Five monophyletic clades (A to E) were formed. Group B showed the highest identity (95%), including 6 mammalian aquaporins, including AQP3. A. fumigatus aquaporin shared the highest identity with Malassezia sympodialis (35%). Both human and A. fumigatus aquaporins featured three linear and three discontinuous epitopes, with a root mean square deviation (RMSD) of 1.006. Conclusion: Possible linear and conformational epitopes on AQP3 were identified. High identity in one antigenic region suggests molecular mimicry between human and A. fumigatus aquaporins, potentially leading to autoreactivity and cross-reactivity. Further in vitro and in vivo studies are needed to confirm these findings.

Stapled peptides are a promising class of molecules with potential as highly specific probes of protein-protein interactions and as therapeutics. Hydrocarbon stapling affects the peptide properties through the interplay of two factors: enhancing the overall hydrophobicity and constraining the conformational flexibility. By constructing a series of virtual peptides, we study the role of each factor in modulating the structural properties of a hydrocarbon stapled peptide PM2 which has been shown to enter cells, engage its target MDM2 and activate p53. Hamiltonian replica exchange molecular dynamics (HREMD) simulations suggest that hydrocarbon stapling favors helical populations of PM2 through a combination of the geometric constraints and the enhanced hydrophobicity of the peptide. To further understand the conformational landscape of the stapled peptides along the binding pathway, we performed HREMD simulations by restraining the peptide at different distances from MDM2. When the peptide approaches MDM2, the binding pocket undergoes dehydration which appears to be greater in the presence of the stapled peptide compared to the linear peptide. In the binding pocket, the helicity of the stapled peptide is increased due to the favorable interactions between the peptide residues as well as the staple and the micro-environment of the binding pocket, contributing to enhanced affinity. The dissection of the multi-facet mechanism of hydrocarbon stapling into individual factors not only deepens fundamental understanding of peptide stapling, but also provides guidelines in the design of new stapled peptides.

Ultrasonographic Manifestations ofMultiple TuberousXanthomas on Bilateral Buttocks with Hypercholesterolemia: One rare case reportDongmei Li a , Lei Wang, MDb ,a University of Electronic Science and Technology, Chengdu 610072, China.b Department of Medical Ultrasound, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China.