Burden of disease, pain catastrophizing, and central sensitization in relation to work-related issues in young spondyloarthritis patients.

Introduction: Spondyloarthritis (SpA) is a common rheumatic inflammatory disease and can impact patients' work productivity. We aimed to evaluate the impact of pain catastrophizing and central sensitization on work outcomes in young SpA patients and determine the predictive factors of work productivity loss. Material and methods: We performed a cross-sectional study over 6 months. We included patients aged between 18 and 50 years old, diagnosed with axial or peripheral SpA. Pain catastrophizing and central sensitization were assessed using the Pain Catastrophizing Scale (PCS) and Central Sensitization Inventory (CSI) questionnaire, respectively. Impact of SpA on work productivity and activity impairment during and outside of work was measured with the Work Productivity and Activity Impairment Questionnaire (WPAI: Spondyloarthritis). Results: A total of 72 patients were enrolled, with a median age of 39 years (28.3-46), 65.3% men, and 54.4% working patients. Median scores of activity impairment outside of work, and work productivity loss were 50% (40-70), and 50% (40-60), respectively. Median absenteeism and presenteeism scores were 0% (IQR 0-7), and 100% (IQR 86.5-100), respectively. Regarding work-related outcomes: activity impairment was positively correlated with CSI and PCS; presenteeism was significantly associated with male sex (p = 0.009); and work productivity loss was positively associated with anxiety, depression, and poor quality of life. Multivariate regression analysis identified predictive factors of work productivity loss: male sex, poor quality of life, and prolonged morning stiffness. Conclusions: Assessment of the impact of pain catastrophizing and central sensitization on work-related outcomes in patients with SpA is important to understand the burden of illness and to identify early those in need of interventions in clinical practice.

Association of Muscle Strength, Psychological Factors, and Central Sensitization With Movement-Evoked Pain in Patients With Nonspecific Chronic Low Back Pain: The BACKFIT Project.

BACKGROUND: People with chronic pain might evade certain movements to prevent their experience of pain. Movement-evoked pain (MEP) might induce lower functionality during daily activities. HYPOTHESIS: (1) MEP after physical fitness tests would vary depending on the main musculature involved in the test; (2) physical and psychological factors would be associated with MEP in patients with NSCLBP. STUDY DESIGN: Cross-sectional design. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 104 (69 women) patients aged 51.0 ± 10.3 years with NSCLBP participated. MEP was measured with a visual analog scale (VAS) at baseline and immediately after performing each physical fitness test, that is, the Biering-Sørensen, prone bridging, handgrip, chair-stand, and 8-foot time-up-and-go tests, measuring back extensor, back flexor, upper- and lower-body muscle strength, and motor agility, respectively. Global muscle strength was calculated with normalized index (z-score) procedure. Depression, anxiety, pain catastrophizing, and central sensitization were assessed with the Beck Depression Inventory II, State Trait Anxiety Inventory I, Pain Catastrophizing Scale, and Central Sensitization Inventory (CSI), respectively. RESULTS: Patients showed greater pain after completion of the Biering-Sørensen (mean difference 95% CI, 0.02, 1.11), prone bridging (0.15, 1.21), lower pain after handgrip (-1.46, -0.52), and the 8-foot time-up-and-go (-1.43, 0.46) tests (all P ≤ 0.04). Lower global muscular strength (ß between -0.18 and -0.30), and greater pain catastrophizing (ß = 0.16), and CSI scoring (ß between 0.18 and 0.27) were associated with greater MEP (all P ≤ 0.04). CONCLUSION: Greater MEP was observed after tests measuring core musculature strength than after tests measuring distal (limbs) strength and agility. Greater MEP was overall associated with lower muscle strength, greater pain catastrophizing, and central sensitization. CLINICAL RELEVANCE: Fitness testing might be implemented as a complementary tool for the monitoring of NSCLBP in clinical settings.

Assessing and Comparing Potential Allergenicity of Two Partially Hydrolyzed Whey-Based Formulas for Infants: A Population-Based Study in China.

SCOPE: In cases where breast milk is unavailable or inadequate, hydrolyzed infant formula is recommended as the primary alternative. The aim of this study is to assess and compare the allergenicity of two partially hydrolyzed whey-based formulas (PHF-Ws) using serum samples from patients with cow's milk allergy (CMA). METHODS AND RESULTS: LC-MS/MS technology is used to investigate the peptide distribution in both samples. The immunoreactivity of two PHF-Ws in 27 serum samples from 50 Chinese infants (02 years) with CMA is analyzed. The results demonstrate that even with a similar a degree of hydrolysis (DH), primary protein sources, peptides with molecular weights <5 kDa, and differences in the number of residual allergenic epitopes in the hydrolyzed peptide segments can lead to varying immune responses. CONCLUSION: The two PHF-Ws have notably high intolerance rates, exceeding 10% among infants with CMA. Therefore, suggesting that PHF-Ws may not be suitable for infants and children with CMA in China.

Mirror-Image Pain Update: Complex Interactions Between Central and Peripheral Mechanisms.

The appearance of contralateral effects after unilateral injury has been shown in various experimental pain models, as well as in clinics. They consist of a diversity of phenomena in contralateral peripheral nerves, sensory ganglia, or spinal cord: from structural changes and altered gene or protein expression to functional consequences such as the development of mirror-image pain (MP). Although MP is a well-documented phenomenon, the exact molecular mechanism underlying the induction and maintenance of mirror-like spread of pain is still an unresolved challenge. MP has generally been explained by central sensitization mechanisms leading to facilitation of pain impulse transfer through neural connections between the two sides of the central nervous system. On the contrary, the peripheral nervous system (PNS) was usually regarded unlikely to evoke such a symmetrical phenomenon. However, recent findings provided evidence that events in the PNS could play a significant role in MP induction. This manuscript provides an updated and comprehensive synthesis of the MP phenomenon and summarizes the available data on the mechanisms. A more detailed focus is placed on reported evidence for peripheral mechanisms behind the MP phenomenon, which were not reviewed up to now.

Evaluating Sensitization-Associated, Neuropathic-Like Symptoms and Psychological Factors in Patients with Interstitial Lung Disease.

The aims of this study were to phenotype pain in patients with interstitial lung disease (ILD) by investigating the association between sensitization-associated symptoms with quality of life, anxiety/depression, pain catastrophizing and kinesiophobia levels, and, identifying those risk factors explaining the variance of quality of life in individuals with ILD and pain. One hundred and thirty-two (38.6% women, mean age: 70, SD: 10.5 years) patients with ILD completed clinical (age, sex, height, weight), psychological (Hospital Anxiety and Depression Scale, HADS and the Pittsburgh Sleep Quality Index, PSQI), and health-related quality of life (EQ-5D-5L) variables as well as the Central Sensitization Inventory (CSI), the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), Pain Catastrophizing Scale (PCS) and Tampa Scale for Kinesiophobia (TSK-11) questionnaires. The prevalence of sensitization-associated symptomatology (CSI), neuropathic-like features (S-LANSS), anxiety symptoms, depressive symptoms or poor sleep was 20.5%, 23.5%, 23.6%, 22.9% or 51.6%. Significant associations between CSI, S-LANSS, HADS-A, HADS-D, PCS, TSK-11 and EQ-5D-5L (.220

Nonlinear Photochromic Reaction Based on Sensitizer-Free Triplet-Triplet Annihilation in a Perylene-Substituted Rhodamine Spirolactam.

Nonlinear photochromic reactions that work with weak incoherent light are important for molecular operation with high spatial resolution, and multiple photofunctions based on single molecules. However, nonlinear photochromic compounds generally require complex molecular design, restricting accessibility in various fields. Herein, we report nonlinear photochromic properties in a perylene-substituted rhodamine spirolactam derivative (Rh-Pe), which is synthesized from rhodamine B in facile procedures. Direct excitation of Rh-Pe produces the triplet excited state via the charge-transfer (CT) state. The triplet excited state causes triplet-triplet annihilation to bring the generation of the intensely-colored ring-open form with the nonlinear behavior. Furthermore, green- and red-light-induced photochromism was achieved in Rh-Pe using triplet sensitizers, although Rh-Pe can be directly excited only by ultraviolet and blue light. Our findings are expected to contribute to the development of photofunctional materials showing nonlinear behavior and low-energy light responsivity.

The Prevalence of IgE-Mediated Food Allergy and Other Allergic Diseases in the First 10 Years: The Population-Based, Longitudinal HealthNuts Study.

BACKGROUND: There are limited longitudinal data on the population prevalence of allergic conditions during childhood, and few studies have incorporated the reference standard oral food challenge to confirm food allergy. OBJECTIVE: To describe the population prevalence of IgE-mediated food allergy, eczema, asthma, and rhinitis at ages 6 and 10 years in Melbourne, Australia. METHODS: The HealthNuts study recruited 5,276 1-year-old infants in Melbourne, Australia, with repeat assessments at ages 6 and 10 years. At ages 6 and 10 years, carers completed a questionnaire on symptoms and doctor diagnosis of allergic conditions (International Study of Asthma and Allergies in Children). Children were invited to attend a clinic assessment including skin prick test, lung function tests, and oral food challenges when indicated. To minimize the impact of attrition bias, prevalence estimates among participants at ages 6 and 10 years were weighted to reflect characteristics of the whole cohort at recruitment. RESULTS: In total, 4,455 and 4,065 families participated at ages 6 and 10 years, respectively (84% and 77% of the original cohort). Of those, 73% and 55% of participants ages 6 and 10 years, respectively, completed clinical assessments. Overall, 36.5% (95% CI, 34.8-38.2) and 38.2% (95% CI, 36.5-40.1%) of 6- and 10-year-olds had at least one current allergic disease, and around one third of those had two or more allergic diseases. Food allergy occurred in 6.4% (95% CI, 5.6-7.2) of 6-year olds and 6.3% (95% CI, 5.5-7.2) of 10-year-olds. Among infants with challenge-confirmed food allergy in infancy, 45% had persistent disease at age 10 years. The prevalence of current diagnosed asthma at ages 6 and 10 years were 12.1% (95% CI, 10.9-13.3) and 13.1% (95% CI, 11.9-14.4), respectively, current eczema decreased slightly from 15.3% (95% CI, 14.1-19.7) at age 6 years to 12.9% (95% CI, 11.7-14.2) at age 10 years, and current rhinitis increased from 15.1% (95% CI, 13.9-16.5) at age 6 years to 25.0% (95% CI, 23.4-26.7) at age 10 years. CONCLUSIONS: Allergic diseases affect 40% of primary school-age children; one third have multiple allergic diagnoses. Challenge-confirmed food allergy prevalence remains high, and 45% of infants with food allergy have persistent disease to age 10 years.

Preventive allergen immunotherapy with inhalant allergens in children.

The efficacy and safety of preventive allergen immunotherapy (pAIT) in children are currently under investigation. Here, we provide an overview of pAIT with respiratory allergens concerning the prevention of new sensitizations, allergic disease onset and progression as well as further immunomodulatory effects. Three databases were searched for clinical pAIT studies in children. Selected publications were reviewed for preventive outcomes according to prevention level (primary, secondary, and tertiary), allergen type, administration route, dose, and treatment duration. The primary prevention approach appears safe but showed no allergen-specific effect on new sensitizations. Secondary prevention seems feasible and may induce regulatory T cell-mediated immunotolerance. The number of studies at these prevention levels is limited. Tertiary prevention with grass and/or tree pollen-based pAIT has shown efficacy in preventing disease progression from allergic rhinitis/conjunctivitis to asthma. Data on tertiary pAIT with house dust mites and other allergen types are inconclusive. Subcutaneous and sublingual routes appear similarly effective, but head-to-head comparative paediatric studies are scarce. Additionally, there are fewer placebo-controlled studies. Nevertheless, immunomodulatory outcomes of pAIT are encouraging. Currently, limited but favourably suggestive evidence is available for preventing respiratory allergic diseases in children by pAIT. Primary and secondary prevention have potential and warrant further investigation through well-designed studies.

Vitamin D level is inversely related to allergen sensitization for risking atopic dermatitis in early childhood.

Background: There are few studies concerning the impact of serum vitamin D status on the risk of allergen sensitization and atopic dermatitis (AD) during early childhood. Method: Children with AD and age-matched healthy controls (HC) were prospectively enrolled at age 0.5, 2, and 4 years. Serum 25-hydroxyvitamin D (25[OH]D) level was measured using Elecsys Vitamin D Total assay. The study utilized the ImmunoCAP assay to analyze specific IgE for food and inhalant allergens, along with total serum IgE levels. It explored the connection between vitamin D levels and allergen sensitization, as well as their influence on AD at different ages. Results: A total of 222 children including 95 (59 AD and 36 HC), 66 (37 AD and 29 HC), and 61 (32 AD and 29 HC) children were classified at age 0.5, 2, and 4 years, respectively. In children with AD, there was a significantly lower vitamin D level at age 2 and 4, but a significantly higher prevalence of food and mite sensitization at all ages in comparison with HC (P < 0.001). Vitamin D level was found to be inversely related to the prevalence of allergen sensitization at age 4 (P < 0.05). However, vitamin D level appeared to have high importance for allergen sensitization at all ages and AD at age 2 and 4 years. Conclusion: Vitamin D deficiency is strongly associated with heightened prevalence of allergen sensitization, potentially increasing the susceptibility to AD in early childhood.

The transcriptomic signature of respiratory sensitizers using an alveolar model.

Environmental contaminants are ubiquitous in the air we breathe and can potentially cause adverse immunological outcomes such as respiratory sensitization, a type of immune-driven allergic response in the lungs. Wood dust, latex, pet dander, oils, fragrances, paints, and glues have all been implicated as possible respiratory sensitizers. With the increased incidence of exposure to chemical mixtures and the rapid production of novel materials, it is paramount that testing regimes accounting for sensitization are incorporated into development cycles. However, no validated assay exists that is universally accepted to measure a substance's respiratory sensitizing potential. The lungs comprise various cell types and regions where sensitization can occur, with the gas-exchange interface being especially important due to implications for overall lung function. As such, an assay that can mimic the alveolar compartment and assess sensitization would be an important advance for inhalation toxicology. Some such models are under development, but in-depth transcriptomic analyses have yet to be reported. Understanding the transcriptome after sensitizer exposure would greatly advance hazard assessment and sustainability. We tested two known sensitizers (i.e., isophorone diisocyanate and ethylenediamine) and two known non-sensitizers (i.e., chlorobenzene and dimethylformamide). RNA sequencing was performed in our in vitro alveolar model, consisting of a 3D co-culture of epithelial, macrophage, and dendritic cells. Sensitizers were readily distinguishable from non-sensitizers by principal component analysis. However, few differentially regulated genes were common across all pair-wise comparisons (i.e., upregulation of genes SOX9, UACA, CCDC88A, FOSL1, KIF20B). While the model utilized in this study can differentiate the sensitizers from the non-sensitizers tested, further studies will be required to robustly identify critical pathways inducing respiratory sensitization.

Tolerance induction through early feeding to prevent food allergy in infants and children with sensitization against food allergens (TIFFANI): rationale, study design, and methods of a randomized controlled trial.

BACKGROUND: Children with sensitization against foods have to be orally food-challenged before eating these foods for the first time. However, the waiting time for an oral food challenge (OFC) in Germany is about 3-6 months. In contrast, there are hints that an early introduction of allergenic foods might be protective regarding the development of food allergy. The aim of this clinical trial is therefore to investigate, whether an introduction and regular consumption of small amounts of food allergens is safe and will result in an increase of tolerance in children with sensitization against food allergens with unknown clinical relevance. METHODS: In this randomized, placebo-controlled, double-blind, single-center trial, 138 children (8 months to 4 years of age) sensitized to the target allergen(s) hen's egg, cow's milk, peanuts, and/or hazelnuts with unknown clinical relevance will be randomized in a 1:1 ratio to either an active or a placebo group, daily receiving a rusk-like biscuit powder with or without the target allergen(s) for 3-6 months until an OFC will be performed in routine diagnostics. The primary endpoint is an IgE-mediated food allergy to the primary target allergen, after the interventional period. DISCUSSION: Children with sensitization against food allergens with unknown clinical relevance often have to avoid the corresponding foods for several months until an OFC is performed. Therefore, the "window of opportunity" for an early preventive introduction of allergenic foods might be missed. This trial will assess whether an introduction of small allergen amounts will favor tolerance development in these children. TRIAL REGISTRATION: German Clinical Trials Register DRKS00032769. Registered on 02 October 2023.

Prenatal and postnatal cocaine exposure enhances the anxiety- and depression-like behaviors in rats during cocaine withdrawal.

Prenatal drug exposure is a public health problem, which results in profound behavioral problems during childhood and adolescence, mainly represented by an increase in the risk of cocaine abuse at an early age. In rodents, prenatal and postnatal cocaine exposure enhanced locomotor activity and cocaine- or nicotine-induced locomotor sensitization. Various authors consider that the adverse emotional states (anxiety and depression) that occur during cocaine withdrawal are the main factors that precipitate, relapse, and increase chronic cocaine abuse, which could increase the risk of relapse of cocaine abuse. Therefore, the objective of this study was to characterize anxiety- and depression-like behaviors at different times (30, 60, 90, and 120 days) of cocaine withdrawal in rats born to females exposed prenatally and postnatally to cocaine. A group of pregnant female Wistar rats were administered daily from day GD0 to GD21 with cocaine (cocaine preexposure group), and another group of pregnant female rats was administered daily with saline (saline preexposure group). Of the litters resulting from the cocaine-pre-exposed and saline-pre-exposed pregnant female groups, only the male rats were used for the recording of the anxiety- and depression-like behaviors at different times (30, 60, 90, and 120 days) of cocaine withdrawal The study found that prenatal and postnatal cocaine exposure dose-dependent enhanced anxiety- and depression-like behaviors. This suggests that prenatal and postnatal cocaine exposure can result in enhanced vulnerability to cocaine abuse in young and adult humans.

The Role of Inhalant Allergens on the Clinical Manifestations of Atopic Dermatitis.

BACKGROUND: Inhalant allergens provide a source of environmental factors that contribute to the development of clinical symptoms in patients with atopic dermatitis (AD). OBJECTIVE: To review the relationship between inhalant allergens and AD. METHODS: A literature review was conducted using three databases: PubMed/MEDLINE, ClinicalKey, and Web of Science. Search terms, including "atopic dermatitis," "atopic eczema," and "eczema," were used in combination with "inhalant allergen," "inhaled allergen," and "aeroallergen" to identify relevant published manuscripts that highlight the relationship between AD and exposures to inhalant allergens. RESULTS: Fifteen articles were suitable for review. The studies included in the review investigated the effect of inhalant allergens on the clinical manifestations of AD through bronchial provocation, direct skin contact, and allergen sensitization. CONCLUSION: There is a significant relationship between exposures to inhalant allergens and AD. Inhalant allergens may aggravate AD symptoms by either bronchial provocation or direct skin contact. Sensitization of inhalant allergens, mainly house dust mites, follows a specific age-related pattern.

Impact of insulin sensitization on metabolic and fertility outcomes in women with polycystic ovary syndrome and overweight or obesity-A systematic review, meta-analysis, and meta-regression.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. This systematic review, meta-analysis, and meta-regression aims to compare the effect of insulin sensitizer pharmacotherapy on metabolic and reproductive outcomes in women with PCOS and overweight or obesity. We searched online databases MEDLINE via OVID, EMBASE, Clinicaltrials.gov, and EudraCT for trials published from inception to November 13, 2023. Inclusion criteria were double-blind, randomized controlled trials in women diagnosed with PCOS, body mass index (BMI) ≥ 25 kg/m2, which reported metabolic or reproductive outcomes. The intervention was insulin sensitization pharmacotherapy versus placebo or other agents. The primary outcomes were changes from baseline BMI, fasting blood glucose, and menstrual frequency. Nineteen studies were included in this review. Metformin had the most significant effect on the fasting plasma glucose and body mass index. Insulin sensitizer pharmacotherapy significantly reduced fasting plasma glucose, body mass index, fasting serum insulin, HOMA-IR, sex hormone binding globulin, and total testosterone, but the effect size was small. There was a lack of menstrual frequency and live birth data. The results indicate a role for insulin sensitizers in improving the metabolic and, to a lesser degree, reproductive profile in these women. Further research should examine insulin sensitizers' effects on objective measures of fecundity.

Unveiling the therapeutic potential of Dl-3-n-butylphthalide in NTG-induced migraine mouse: activating the Nrf2 pathway to alleviate oxidative stress and neuroinflammation.

BACKGROUND: Migraine stands as a prevalent primary headache disorder, with prior research highlighting the significant involvement of oxidative stress and inflammatory pathways in its pathogenesis and chronicity. Existing evidence indicates the capacity of Dl-3-n-butylphthalide (NBP) to mitigate oxidative stress and inflammation, thereby conferring neuroprotective benefits in many central nervous system diseases. However, the specific therapeutic implications of NBP in the context of migraine remain to be elucidated. METHODS: We established a C57BL/6 mouse model of chronic migraine (CM) using recurrent intraperitoneal injections of nitroglycerin (NTG, 10 mg/kg), and prophylactic treatment was simulated by administering NBP (30 mg/kg, 60 mg/kg, 120 mg/kg) by gavage prior to each NTG injection. Mechanical threshold was assessed using von Frey fibers, and photophobia and anxious behaviours were assessed using a light/dark box and elevated plus maze. Expression of c-Fos, calcitonin gene-related peptide (CGRP), Nucleus factor erythroid 2-related factor 2 (Nrf2) and related pathway proteins in the spinal trigeminal nucleus caudalis (SP5C) were detected by Western blotting (WB) or immunofluorescence (IF). The expression of IL-1ß, IL-6, TNF-α, Superoxide dismutase (SOD) and malondialdehyde (MDA) in SP5C and CGRP in plasma were detected by ELISA. A reactive oxygen species (ROS) probe was used to detect the expression of ROS in the SP5C. RESULTS: At the end of the modelling period, chronic migraine mice showed significantly reduced mechanical nociceptive thresholds, as well as photophobic and anxious behaviours. Pretreatment with NBP attenuated nociceptive sensitization, photophobia, and anxiety in the model mice, reduced expression levels of c-Fos and CGRP in the SP5C and activated Nrf2 and its downstream proteins HO-1 and NQO-1. By measuring the associated cytokines, we also found that NBP reduced levels of oxidative stress and inflammation. Most importantly, the therapeutic effect of NBP was significantly reduced after the administration of ML385 to inhibit Nrf2. CONCLUSIONS: Our data suggest that NBP may alleviate migraine by activating the Nrf2 pathway to reduce oxidative stress and inflammation in migraine mouse models, confirming that it may be a potential drug for the treatment of migraine.

Sensitization-Associated Symptoms and Neuropathic-like Features in Patients with Cervical Dystonia and Pain.

Background: This exploratory study evaluated the presence of sensitization-associated and neuropathic-like symptoms and identified their association with pressure sensitivity, pain, and disability in patients with cervical dystonia (CD). Methods: Thirty-one patients with CD (74.2% women, age: 61.2 years, SD 10.1) participated. Data collected included clinical variables, the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), the Central Sensitization Inventory (CSI), the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI), as well as widespread pressure pain thresholds (PPTs). Results: Patients with CD with pain (n = 20, 64.5%) showed higher scores on the TWSTRS disability subscale and the CSI (p < 0.001), and lower PPTs (p < 0.05). Fifteen patients (15/31, 48%) showed sensitization-associated symptoms (CSI ≥ 40), whereas five of the patients with pain (5/20, 25%) exhibited neuropathic-like symptoms (S-LANSS ≥ 12). The CSI and S-LANSS were positively associated with the TWSTRS, HADS-A and HADS-D, and negatively associated with PPTs. HADS-D and S-LANSS explained 72.5% of the variance of the CSI (r2: 0.725), whereas CSI explained 42.3% of the variance of the S-LANSS (r2: 0.423). Conclusions: Pain is an important source of disability in CD, and may be a consequence of different mechanisms, including sensitization.

Associations between the burdens of comorbid sleep problems, central sensitization, and headache-related disability in patients with migraine.

Objective: Sleep disturbances are common in migraine patients and affect quality of life. Central sensitization (CS) is likely to play a role in the increased severity and chronicity of migraine. We hypothesized that the number of comorbid sleep problems would affect headache-related disability through the effects of central sensitization (CS). Methods: We performed a cross-sectional study including 215 consecutive patients with migraine. Insomnia was defined as a Pittsburgh Sleep Quality Index (PSQI) global score greater than 5. Probable REM sleep behavior disorder (pRBD) was defined as an RBD screening score of 5 or greater. Excessive daytime sleepiness (EDS) was defined as an Epworth Sleepiness Scale score of 10 or higher. Suspected sleep apnea (SA) was defined as patients with snoring or sleep apnea witnessed 3 or more nights a week. CS was assessed by the Central Sensitization Inventory (CSI). Results: Restless legs syndrome, insomnia, EDS, SA and pRBD were observed in 25.6%, 71.6%, 34.4%, 10.2%, and 21.4%, respectively, of the patients. At least one sleep problem was present in 87.0% of the patients. According to the results of the multinomial logistic regression analysis with no sleep problems as a reference, after we corrected for adjustment factors, the Migraine Disability Assessment (MIDAS) score significantly increased when three or more comorbid sleep problems were present. According to our mediation analysis, an increased number of sleep problems had a direct effect on the MIDAS score after we adjusted for other variables, and the CSI score was indirectly involved in this association. Conclusion: The present study showed an association between migraine-related disability and the burden of multiple sleep problems, which was partially mediated by CS.

Incidence of grass and weed sensitization in Bangkok, Thailand: a clinical study.

Background: Allergic rhinitis (AR) is a prevalent public health concern globally, significantly impacting quality of life. In Thailand, the prevalence of AR is rising, with grass and weed pollen identified as primary outdoor triggers. Objectives: This study aimed to (1) assess patterns of pollen sensitization in Thai AR patients and (2) investigate correlations between demographics/clinical data and SPT results. Methods: A total of 121 individuals aged ≥18 years with clinically diagnosed AR were recruited. Skin prick testing (SPT) was performed using a panel of commonly encountered tropical grass and weed pollen extracts. SPT wheal sizes and clinical symptom scores were recorded. Correlations between SPT outcomes and symptom scores were analyzed. Results: Among the participants, 104 (85.95%) exhibited positive SPT reactions to at least one pollen type. Nutsedge (76/121), para grass (57/121), and Bermuda grass (48/121) were the most frequently identified allergens. Hurricane grass elicited the strongest reaction, evidenced by the highest average wheal size (6.2 mm). Poly-sensitization was observed in 77 (63.6%) of the SPT-positive individuals, with most cases involving two different pollen extracts (35/77). Notably, AR severity positively correlated with both average wheal size and the number of positive SPT tests. Conclusion: This study highlights nutsedge, para grass, and Bermuda grass as major allergenic pollen sources for Thai AR patients. Including nutsedge, hurricane grass, and careless weed in clinical SPT panels is recommended for improved diagnostic accuracy. Additionally, the positive correlation between AR severity and pollen reaction strength emphasizes the importance of implementing patient education and avoidance strategies.

Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).

As a member of BET (bromodomain and extra-terminal) protein family, BRD4 (bromodomain­containing protein 4) is a chromatin­associated protein that interacts with acetylated histones and actively recruits regulatory proteins, leading to the modulation of gene expression and chromatin remodeling. The cellular and epigenetic functions of BRD4 implicate normal development, fibrosis and inflammation. BRD4 has been suggested as a potential therapeutic target as it is often overexpressed and plays a critical role in regulating gene expression programs that drive tumor cell proliferation, survival, migration and drug resistance. To address the roles of BRD4 in cancer, several drugs that specifically target BRD4 have been developed. Inhibition of BRD4 has shown promising results in preclinical models, with several BRD4 inhibitors undergoing clinical trials for the treatment of various cancers. Head and neck squamous cell carcinoma (HNSCC), a heterogeneous group of cancers, remains a health challenge with a high incidence rate and poor prognosis. Conventional therapies for HNSCC often cause adverse effects to the patients. Targeting BRD4, therefore, represents a promising strategy to sensitize HNSCC to chemo­ and radiotherapy allowing de­intensification of the current therapeutic regime and subsequent reduced side effects. However, further studies are required to fully understand the underlying mechanisms of action of BRD4 in HNSCC in order to determine the optimal dosing and administration of BRD4­targeted drugs for the treatment of patients with HNSCC.