Symptoms Of Hypersensitivity Research Articles

Allergic contact dermatitis to chlorhexidine in children

Background: Hypersensitivity to chlorhexidine is rare in children. The usefulness of different diagnostic tests for allergic contact dermatitis (ACD) is unknown. Objective: We aim to describe a case series of children with hypersensitivity to chlorhexidine and to compare the results of different diagnostic tests. Patients: Nine children with hypersensitivity to chlorhexidine were included. Only six of these children and their parents consented to a comprehensive allergy assessment, which included the prick test, intradermal test, patch test, and repeated open application test (ROAT). Results: Seven children (78%) presented symptoms of chlorhexidine hypersensitivity within the first 5 years of life; two of them before the age of 1 year. In four children, the dermatitis lesions were suggestive of wound superinfection. All six children who participated in the comprehensive diagnostic evaluation had negative results on the prick test. The immediate-reading intradermal test was positive in one case and uncertain in two cases. The patch test was positive in five cases, and the ROAT was positive in all six cases when using 2% chlorhexidine alcohol solution. Conclusion: ACD to chlorhexidine in children appears to be rare and can be difficult to detect. Clinicians should consider this diagnosis when wounds worsen with chlorhexidine. Although the patch test is the most standardized method for detecting ACD, the ROAT with 2% chlorhexidine alcohol solution was the most sensitive test in our patients.

Cluster Analysis of Migraine-associated Symptoms (CAMS) in youth: A retrospective cross-sectional multicenter study.

To conduct a retrospective cross-sectional multicenter study to validate the relationships between migraine-associated symptoms. Symptoms associated with headache-photophobia and phonophobia, nausea, and/or vomiting-are required criteria for migraine diagnosis based on the International Classification of Headache Disorders-Third Edition (ICHD-3). However, individuals with migraine report high rates of other symptoms (e.g., lightheadedness, difficulty thinking). We recently completed a single-center study assessing the relationships between an expanded set of migraine-associated symptoms. A pre-registered cross-sectional multicenter retrospective analysis was conducted on standardized questionnaire data of youth ages 6-17 years from two headache registries at pediatric tertiary care centers. Cluster Analysis of Migraine-associated Symptoms (CAMS) was implemented to assess associations between 11 migraine-associated symptoms. We explored differences between the two centers, and how CAMS was associated with demographics, including sex and age, and headache burden. There were 10,721 participants who were 66.5% female and had a median (interquartile range) age of 13 (10-15) years. The first three CAMS dimensions accounted for 46.5% of the variance and were consistent across sites. The first dimension indicated those reporting any migraine-associated symptoms were likely to report multiple. The second dimension separated symptoms into those included in ICHD-3 migraine diagnostic criteria and non-ICHD symptoms (e.g., lightheadedness, difficulty thinking). The third dimension separated sensory hypersensitivity and vestibular symptoms. An abundance of migraine-associated symptoms correlated with greater headache severity (Spearman's ρ = 0.18, 95% confidence interval [CI] 0.17-0.20; small effect size) and disability (ρ = 0.26, 95% CI 0.25-0.28; small effect size). We also observed differences in associated symptoms across age and sex. Associations between an expanded set of migraine-associated symptoms are informative for headache burden and reveal intriguing changes across child development and sex. We were able to replicate findings across two centers, indicating that these symptom clusters are inherent to migraine.

Home treatment protocol for dentin hypersensitivity with hydroxyapatite-based biodynamic toothpaste and lactoferrin: a pilot study.

In recent years, there has been a gradual increase in cases of dentin hypersensitivity, often related to gingival recession, enamel abrasion from brushing, and wear of root cementum. This condition can affect patients of all ages but is more common between 20 and 40 years of age, especially in females and individuals with periodontal disease. The study aimed to evaluate and compare the efficacy over time of a product for at-home treatment of dentin hypersensitivity. One hundred five patients aged between 28 and 65 years were recruited, each with at least two hypersensitive teeth due to erosions, abrasions, gingival recessions, and/or periodontal diseases. Participants were selected through the Schiff Test and anamnestic evaluations, with compilation of periodontal records. Patients are instructed to use the product three times a day, to be applied with a soft-bristled toothbrush and/or topically as a gel on teeth with strong sensitivity and deep cervical lesions and gingival recessions. There were no statistically significant differences between measurements at baseline and after scaling. However, significant differences were observed in follow-ups from the 1st to the 8th week, with a progressive decrease in values. The average trend of product efficacy increases over time according to the Schiff Test, with a significant improvement observed at follow-ups conducted after four and eight weeks. The results indicate that the product enriched with biomimetic hydroxyapatite and lactoferrin is effective in reducing the painful symptoms of dentin hypersensitivity and in counteracting the inflammatory state of the supporting tissues.

Revisiting Latex-Fruit Syndrome after 30 Years of Research: A Comprehensive Literature Review and Description of Two Cases.

Thirty years have passed since the concept of latex-fruit syndrome (LFS) was first introduced. Since then, this phenomenon, characterized by cross-reactivity between natural latex rubber allergens and certain fruit allergens, has been extensively studied. This literature review sought to determine the prevalence of LFS in latex-allergic patients, identify the most common cross-reactions with fruit allergens in individuals with LFS, and understand the clinical manifestations of this syndrome. An extensive literature search was carried out using PubMed and Scopus databases, while applying the Preferred Reporting Items for Systematic Reviews and Meta-Analysis methodology. The analysis of original studies revealed a wide variation in LFS prevalence (4-88%) influenced by diverse diagnostic tools, different geographical regions, and the size of study populations. Our findings indicate that the most prevalent allergenic fruits in patients with LFS are banana, avocado, kiwifruit, and papaya. After evaluating the symptoms of the fruit hypersensitivity of patients with LFS, the clinical manifestation of hypersensitivity constituted 73% of systemic allergy symptoms and only 27% of reported symptoms described the localized allergy. Furthermore, the clinical picture of latex-fruit syndrome is illustrated through two cases, one typical and one with an unusual presentation. Their clinical features were assessed and contrasted utilizing different anaphylaxis severity grading criteria. To properly manage LFS, it is essential to establish standardized diagnostic criteria and severity grading systems, as these are crucial for accurate diagnosis and effective treatment.

Patient Perception of Cough in Interstitial Lung Disease; Impact of Cough Hypersensitivity

IntroductionCough is common in interstitial lung disease (ILD) and is associated with disease progression, yet its mechanisms are understudied. We investigated cough hypersensitivity features and impact in ILD.MethodsParticipants with ILD and cough (n = 195) completed a multiple choice and free text questionnaire on cough sensations/triggers and impacts.ResultsThe majority of participants were male (54%), aged > 65 (64%), with idiopathic pulmonary fibrosis (IPF, 75%). Common cough triggers were body position (74%), physical activity (72%), and talking (62%). Common laryngeal sensations were globus (43%), and itch/tickle (42%). Cough impacted everyday life in 55%, and all activities in 31%, causing exhaustion (59%), social embarrassment (70%), urinary incontinence (46% females), and syncope/pre-syncope (12%). The total number of cough-provoking sensations/triggers correlated with impacts; ρ = 0.73, p < 0.001.ConclusionCough hypersensitivity symptoms are prevalent in ILD and detrimentally affect quality of life. Further studies investigating mechanisms of cough hypersensitivity and targeted pharmacotherapy are warranted.

Clinical study of cervical caries treatment the effectiveness by assessing composite restorations condition

Background. Cervical caries is a fairly common teeth pathology and its treatment is carried out in complicated clinical conditions. Therefore, increasing the term of functioning of composite restorations is an urgent task. Aim. Identification of the effectiveness of a differential approach to dissection of hard dental tissues depending on the depth of enamel microcracks and implementation of professional hygiene in the treatment of cervical caries in the short- and long-term periods. Materials &amp; Methods. The study involved 50 people (average age [23.28±5.52] years) in whom cervical caries was treated in 72 teeth. All patients were divided into three equal groups based on the number of restorations according to the selected dissection technique and the chara­cteristics of professional hygiene. The dissection technique depended on the depth of the enamel microcracks in Main Group I (MG I), the dissection was carried out within the limits of clinically intact hard dental tissues in Control Group (CG) and Main Group II (MG II). The dental biofilm was removed from the vestibular surface of the teeth by the method of air-abrasive cleaning using the erythritol-based powder in MG I and MG II, the vestibular surface of the tooth was cleaned of dental deposits with a polishing paste without fluoride in CG. The quality of restorations was assessed based on the United States Public Health Service (USPHS) criteria on the day of restoration, 6 and 12 months later. The effectiveness of the prescribed treatment was identified by the dynamic indicators of the dental pulp electroexcitability and the electrical conductivity of the enamel. Results. There were no partial or completely destroyed restorations in all terms of the observation period. Composite restorations were preserved according to the criteria of "anatomical shape" and "color matching". One year later restoration defects were absent in 61 teeth (84.72%): in MG I – in 22 (91.67%), in CG – in 19 (79.17%), in MG II – in 20 (83.33%). Recurrent caries and symptoms of hypersensitivity were not identified in MG I. A slightly greater effectiveness of the treatment was noted in MG II group in comparison with CG (by 4.16%) that confirms the importance of removing the dental biofilm before restoration by the method of air-abrasive clea­ning using erythritol. Conclusions. The analysis of the state of restorations in the long-term period showed that the dissection technique and the features of professional hygiene affected their quality before restoration. The number of high-quality composite restorations was by 10.42% more on average in MG I than in the other groups. The obtained results make it possible to recommend the proposed method for using in practical dentistry. Keywords: electroodontology, electroodontometry, microcracks.

Revaccination outcomes among adolescents and adults with suspected hypersensitivity reactions following COVID-19 vaccination: A Canadian immunization research network study

BackgroundCOVID-19 vaccination has been associated with anaphylaxis and hypersensitivity reactions. Infectious disease physicians and allergists in the Canadian Special Immunization Clinic (SIC) Network developed guidance for evaluating patients with adverse events following immunization (AEFI) including suspected hypersensitivity. This study evaluated management and adverse event recurrence following subsequent COVID-19 vaccinations. MethodsIndividuals aged 12 years and older enrolled at participating SICs before February 28, 2023 who were referred for suspected or diagnosed hypersensitivity reaction following COVID-19 vaccination, or for prevaccination assessment of suspected allergy to a COVID-19 vaccine component were included. De-identified clinical assessments and revaccination data, captured in a centralized database, were analyzed. The Brighton Collaboration case definition (BCCD) for anaphylaxis (2023 version) was applied. ResultsThe analysis included 206 participants from 13 sites: 26 participants referred for pre-vaccination assessment and 180 participants referred for adverse events following COVID-19 vaccination (15/180 [8.3%] with BCCD confirmed anaphylaxis, 84 [46.7%] with immediate hypersensitivity symptoms not meeting BCCD, 33 [18.3%] with other diagnosed hypersensitivity reactions, and 48 [26.7%] participants with a final diagnosis of non-hypersensitivity AEFI). Among participants referred for AEFIs following COVID-19 vaccination, 166/180 (92.2%) were recommended for COVID-19 revaccination after risk assessment, of whom 158/166 (95.2%) were revaccinated (all with a COVID-19 mRNA vaccine). After revaccination, 1/15 (6.7%) participants with prior anaphylaxis, 1/77 (1.3%) with immediate hypersensitivity not meeting criteria for anaphylaxis and 1/24 (4.2%) with other physician diagnosed hypersensitivity developed recurrent AEFI symptoms that met the BCCD for anaphylaxis.All 26 participants referred pre-vaccination, including 9 (34.6%) with history of polyethylene glycol-asparaginase reactions, were vaccinated without occurrence of immediate hypersensitivity symptoms. ConclusionsMost individuals in this national cohort who experienced a hypersensitivity event following COVID-19 vaccination and were referred for specialist review were revaccinated without AEFI recurrence, suggesting that specialist evaluation can facilitate safe revaccination.

Prevalence and risk factors for milk allergy overdiagnosis in the BEEP trial cohort.

Cow's milk allergy (CMA) overdiagnosis in young children appears to be increasing and has not been well characterised. We used a clinical trial population to characterise CMA overdiagnosis and identify individual-level and primary care practice-level risk factors. We analysed data from 1394 children born in England in 2014-2016 (BEEP trial, ISRCTN21528841). Participants underwent formal CMA diagnosis at ≤2 years. CMA overdiagnosis was defined in three separate ways: parent-reported milk reaction; primary care record of milk hypersensitivity symptoms; and primary care record of low-allergy formula prescription. CMA was formally diagnosed in 19 (1.4%) participants. CMA overdiagnosis was common: 16.1% had parent-reported cow's milk hypersensitivity, 11.3% primary care recorded milk hypersensitivity and 8.7% had low-allergy formula prescription. Symptoms attributed to cow's milk hypersensitivity in participants without CMA were commonly gastrointestinal and reported from a median age of 49 days. Low-allergy formula prescriptions in participants without CMA lasted a median of 10 months (interquartile range 1, 16); the estimated volume consumed was a median of 272 litres (26, 448). Risk factors for CMA overdiagnosis were high practice-based low-allergy formula prescribing in the previous year and maternal report of antibiotic prescription during pregnancy. Exclusive formula feeding from birth was associated with increased low-allergy formula prescription. There was no evidence that practice prescribing of paediatric adrenaline auto-injectors or anti-reflux medications, or maternal features such as anxiety, age, parity and socioeconomic status were associated with CMA overdiagnosis. CMA overdiagnosis is common in early infancy. Risk factors include high primary care practice-based low-allergy formula prescribing and maternal report of antibiotic prescription during pregnancy.

Could cough hypersensitivity symptom profile differentiate phenotypes of chronic cough?

Could cough hypersensitivity symptom profile differentiate phenotypes of chronic cough?

Protein Haptenation and Its Role in Allergy.

Humans are exposed to numerous electrophilic chemicals either as medicines, in the workplace, in nature, or through use of many common cosmetic and household products. Covalent modification of human proteins by such chemicals, or protein haptenation, is a common occurrence in cells and may result in generation of antigenic species, leading to development of hypersensitivity reactions. Ranging in severity of symptoms from local cutaneous reactions and rhinitis to potentially life-threatening anaphylaxis and severe hypersensitivity reactions such as Stephen-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), all these reactions have the same Molecular Initiating Event (MIE), i.e. haptenation. However, not all individuals who are exposed to electrophilic chemicals develop symptoms of hypersensitivity. In the present review, we examine common chemistry behind the haptenation reactions leading to formation of neoantigens. We explore simple reactions involving single molecule additions to a nucleophilic side chain of proteins and complex reactions involving multiple electrophilic centers on a single molecule or involving more than one electrophilic molecule as well as the generation of reactive molecules from the interaction with cellular detoxification mechanisms. Besides generation of antigenic species and enabling activation of the immune system, we explore additional events which result directly from the presence of electrophilic chemicals in cells, including activation of key defense mechanisms and immediate consequences of those reactions, and explore their potential effects. We discuss the factors that work in concert with haptenation leading to the development of hypersensitivity reactions and those that may act to prevent it from developing. We also review the potential harnessing of the specificity of haptenation in the design of potent covalent therapeutic inhibitors.

Network pharmacology and experimental validation to explore the mechanism of Changji'an formula against irritable bowel syndrome with predominant diarrhea

Changji'an Formula (CJAF) is a Chinese herbal compound, which is effective against irritable bowel syndrome with predominant diarrhea (IBS-D) in clinic. However, the molecular mechanism has not been well defined. In the current study, the potential targets and signaling pathways of CJAF against IBS-D were predicted using network pharmacology analysis. The pharmacological mechanisms of CJAF against IBS-D and the potential mechanism were validated by using an IBS-D mouse model induced by enema with trinitrobenzene-sulfonic acid (TNBS) plus with restraint stress and further intervened with CJAF. A total of 232 active compounds of CJAF were obtained, a total of 397 potential targets for the active ingredients were retrieved and a total of 219 common targets were obtained as the potential targets of CJAF against IBS-D. GO and KEGG enrichment analyses showed that multiple targets were enriched and could be experimentally validated in a mouse model of IBS-D. The mechanisms were mainly converged on the immune and inflammatory pathways, especially the NF-κB, TNF and IL-17 signaling pathway, which were closely involved in the treatment of CJAF against IBS-D. Animal experiment showed that CJAF alleviated visceral hypersensitivity and diarrhea symptom of IBS-D. CJAF also restored the histological and ultrastructure damage of IBS-D. The result of Western blot showed that CJAF upregulated colonic tight junction proteins of ZO-1, Occludin and Claudin-1. Further results demonstrated that CJAF inhibited the protein expression of NF-κB/NLRP3 inflammasome pathway targets and downregulated proinflammatory mediators of IL-1β, IL-18, TNF-α. In conclusion, CJAF could effectively reduce inflammatory response and alleviate visceral hypersensitivity as well as diarrhea symptom of IBS-D by inhibiting the NF-κB/NLRP3 signaling pathway. This study not only reveals the mechanism of CJAF against IBS-D, but also provides a novel therapeutic strategy for IBS-D.

Inferior long-term Results of a Prospective Randomized Controlled Trial initially demonstrating enhanced Sensory Nerve Recovery using a Chitosan Nerve Tube.

Traumatic peripheral nerve injuries can result in significant functional impairments and long-term sequelae. This study evaluated the long-term outcomes of a chitosan tube implantation protecting the epineural coaptation after peripheral nerve injuries using two different tube versions (V 1.0 and V 2.0 with different wall thickness and resorption characteristics) compared to a control group. The study focused on pain levels, sensory function, and overall functional outcomes. Patients who received tube implantation around direct coaptation sites of digital nerves were prospectively randomized and compared to control patients without additional tube protection. Pain levels, sensory function, grip force, and functional scores were assessed at different time points, ranging from three months to five years after the procedure. Furthermore, biodegradation of the tubes was measured via high-resolution MR-neurography (MRN) and categorized. Long-term evaluation revealed that patients with V 1.0 had higher pain levels compared to the control group after five years. They also reported more symptoms of numbness and hypersensitivity. V 2.0 patients exhibited higher pain levels at three months, which did not persist at six months. However, they showed compromised sensory function, with higher values of two-point discrimination compared to V 1.0 and the control group. No differences were found in grip force or functional scores between the groups. MRI displayed remnants of implants even in long-term follow-up. The findings suggest potential limitations due to pain increase and impaired sensory function associated with tube implantation in the long term. However, in the short term, the material seemed to have a protective effect (as published previously). The resorption process was not completed at the end of the observation period of five years. This might explain the prolonged scarring and inferior long-term results. Future research should focus on improving tube materials and design to minimize adverse effects and enhance functional outcomes in patients with peripheral nerve injuries.

Gamma activity in Autism Spectrum Disorder: Enhanced response to visual input

IntroductionAutism spectrum disorder (ASD) is a childhood onset neurodevelopmental condition, that leads to permanent disability in a high proportion of cases. ASD is associated with a heterogeneous symptom presentation, which - besides social interaction and communication difficulties - encompasses altered sensory reactivity, including excessive hyper-sensitivity to stimuli, especially in the visual domain. Meta-analyses of fMRI studies revealed increased reactivity in visual task conditions in the temporal and occipital brain regions. Neural oscillations in the EEG gamma band are viewed as a candidate neurobiological marker for higher order sensory and perceptual processes, and social interactions.ObjectivesWe investigated changes in gamma activity in the EEG in the eyes open (EO) vs. eyes closed (EC) condition in order to identify the neurobiological underpinning of the enhanced sensitivity to visual input in ASD as compared to typically developing (TD) subjects.MethodsEEGs were obtained in EC and EO condition in ASD (N=23) and TD subjects (N=24) in an ongoing study. For EEG recording we used a high-density 128-channel BioSemi system, with 0.5 Hz frequency resolution. The spectral power in the gamma band (30-100Hz) was quantified by the power spectral density. To investigate whether changes in the gamma band were linked to changes in arousal instead of enhanced visual processing, we also examined alterations in the alpha band (8-13Hz) in the EO condition. Spectral power changes were determined for each EEG channel by computing the difference between the EC and EO conditions (EO-EC).ResultsSpectral power in the gamma band showed changes in the opposite direction in the two study groups: ASD subjects manifested significant (p&lt;0.05) increase, while TD subjects had a decrease in the EO vs. EC condition in the temporal and occipital brain regions. By contrast, the changes in the alpha band were similar, with both groups exhibiting a spectral power decrease in the EO compared to the EC condition.ConclusionsIn ASD, an enhancement of gamma activity is present in the EO as compared to the EC condition in the posterior brain areas. These brain areas are involved in the processing of visual information, and gamma activity is considered as a measure of perceptual processes. Thus, the gamma alterations in the EO vs. EC condition may underlie the hyper-sensitivity symptoms to visual stimuli in ASD, and EEG can offer a simple to use tool to delineate the neurobiological foundation of the symptom presentation.Funding statement: Hungarian Brain Research program,#NAP2022-I-4/2022Disclosure of InterestNone Declared

Alpha-Tryptase as a Risk-Modifying Factor for Mast Cell-Mediated Reactions.

To provide an overview on the current understanding of genetic variability in human tryptases and summarize the literature demonstrating the differential impact of mature tryptases on mast cell-mediated reactions and associated clinical phenotypes. It is becoming increasingly recognized that tryptase gene composition, and in particular the common genetic trait hereditary alpha-tryptasemia (HαT), impacts clinical allergy. HαT has consistently been associated with clonal mast cell disorders (MCD) and has also been associated with more frequent anaphylaxis among these patients, and patients in whom no allergic trigger can be found, specifically idiopathic anaphylaxis. Additionally, more severe anaphylaxis among Hymenoptera venom allergy patients has been linked to HαT in both retrospective and prospective studies. An increased relative number of α-tryptase-encoding gene copies, even in the absence of HαT, has also been associated with systemic mastocytosis and has been shown to positively correlate with the severity of mast cell-mediated reactions to vibration and food. These findings may be due to increased generation of α/β-tryptase heterotetramers and differences in their enzymatic activity relative to β-tryptase homotetramers. HαT is a naturally occurring overexpression model of α-tryptase in humans. Increased relative α-tryptase expression modifies immediate hypersensitivity symptoms and is associated with more frequent and severe mast cell-mediated reactions, ostensibly due to increased α/β-tryptase heterotetramer production.

Effect of exogenous tannic acid on reduction of biogenic amines and citrinin in monascal soybean and metabolomics analysis

Biogenic amines (BAs) are often involved in human pathologies such as hypersensitivity symptoms. This research studied the effect of exogenous tannic acid (ETA) supplementation at various concentrations (0–20 mg/mL) on BA and mycotoxin citrinin levels in monascal soybean (MSB) and conducted a metabolomics analysis to estimate the metabolites in MSB. Addition of 20 mg/mL ETA decreased BA and citrinin levels in MSB after 25 days of fermentation by > 1.76 and >2.46 fold, respectively compared to the treatment without ETA addition. After 10 days of fermentation, the number of enterococci in MSB after treatment of >10 mg/mL ETA decreased by a minimum of 1.33 log CFU/g. ETA promoted large amounts of monacolin K, Monascus pigments, and free amino acids (FAAs) in MSB. A heatmap-HCA revealed that the 20 mg/mL ETA treatment was optimal, as confirmed by the VIP score and PCA. During MSB fermentation, seven notable metabolic pathways were identified as 1. phenylalanine metabolism, 2. arginine and proline metabolism, 3. phenylalanine, tyrosine, and tryptophan biosynthesis, 4. arginine biosynthesis, 5. histidine metabolism, 6. tryptophan metabolism, and 7. tyrosine metabolism. Supplementation of ETA in soybean substrate led to reduced BA and citrinin levels in MSB. The metabolomics analysis provide a better understanding of metabolite correlations, especially FAA formation and BA biosynthesis.

Exploratory study of cold hypersensitivity in Japanese women: genetic associations and somatic symptom burden

Temperature perception is essential for humans to discern the environment and maintain homeostasis. However, some individuals experience cold hypersensitivity, characterized by a subjective feeling of coldness despite ambient environmental temperatures being normal, the underlying mechanisms of which are unknown. In this study, we aimed to investigate the relationship between subjective cold symptoms and somatic burden or single nucleotide polymorphisms to understand the causes of cold hypersensitivity. We conducted an online questionnaire survey [comprising 30 questions, including past medical history, subjective symptoms of cold hypersensitivity, and the Somatic Symptom Scale-8 (SSS-8)]. Respondents were 1200 Japanese adult female volunteers (age: 20–59 years), recruited between April 21 and May 25, 2022, who were customers of MYCODE, a personal genome service in Japan. Among the 1111 participants, 599 (54%) reported cold hypersensitivity. Higher cold hypersensitivity severity was positively associated with the SSS-8 scores. Additionally, a genome-wide association study for cold hypersensitivity was conducted using array-based genomic data obtained from genetic testing. We identified 11 lead variants showing suggestive associations (P < 1 × 10–5) with cold hypersensitivity, some of which showed a reasonable change in expression in specific tissues in the Genotype-Tissue Expression database. The study findings shed light on the underlying causes of cold hypersensitivity.

Hydroxyapatite as an active ingredient in oral care: an international symposium report

Hydroxyapatite, Ca5(PO4)3(OH), is a bioinspired active ingredient for preventive oral health care. The use of hydroxyapatite in the prevention of oral diseases has gained interest, particularly in recent years. Hydroxyapatite can be used in office and for daily oral care (e.g. in toothpastes and mouthwashes). The first clinical efficacy studies on caries prevention and reduction of symptoms of dentin hypersensitivity were conducted in the 1980s. These were followed by various in vitro and in situ studies and several more recent clinical trials. A number of systematic reviews and meta-analyses on the use of hydroxyapatite in preventing oral health problems have been published. Summarizing these data, hydroxyapatite is a versatile active ingredient with multiple benefits that include caries prevention, relief from dentin hypersensitivity and tooth whitening. Since this calcium phosphate mineral has an excellent biocompatibility, it is safe for all patient groups. This interdisciplinary review gives an overview of the developments in hydroxyapatite research, highlights the research progress made regarding hydroxyapatite as a biomimetic active ingredient and summarizes the state-of-the-art evidence in support of hydroxyapatite efficacy.

Nine-Month Continuous Fremanezumab Prophylaxis on the Response to Triptans and Also on the Incidence of Triggers, Hypersensitivity and Prodromal Symptoms of Patients with High-Frequency Episodic Migraine.

Objective: To investigate whether the incidence of triggers, prodromal symptoms, hypersensitivity symptoms accompanying headache and responses to triptans were modified during a continuous 9-month fremanezumab therapy for migraine prophylaxis. Patients and methods: We studied 63 patients with high-frequency episodic migraine (HFEM). Enrolled patients received fremanezumab for nine consecutive months before defining the response rates and being stratified into treatment responders (≥50-74% reduction in monthly headache days (MHDs)), super responders (≥75%), partial non-responders (<50%) and super non-responders (<30%). Through headache diaries, patients provided data in order to document the impact of fremanezumab on the incidence of triggers, associated symptoms followed by headache and response to triptans (the use of the migraine treatment optimization questionnaire-4 (mTOQ-4)) during the 9-month treatment period. Results: Fremanezumab had early (after 3 monthly cycles) beneficial effects on the response to triptans in the majority of responders with relevant increases in mTOQ-4 scoring, but also in half of partial non-responders. A significant reduction in median days with migraine-associated symptoms was seen in responders after 6 months of therapy with fremanezumab, mostly for osmophobia, photophobia, phonophobia and nausea/vomiting, but partial non-responders also benefited. Likewise, the incidence of self-reported prodromal symptoms was significantly reduced in responders and was modestly diminished in partial non-responders. Triggers remained unaffected in both responders and non-responders. Conclusions: Fremanezumab given for at least 6-9 months may exert neuromodulatory effects in the migraine brain. These effects could result both in the inhibition of migraine chronification, but also in the diminishing of the magnitude of migraine-associated symptoms, mostly in responders and in partial non-responders.

The omega-3 postbiotic trans-10-cis-15-octadecadienoic acid attenuates contact hypersensitivity in mice through downregulation of vascular endothelial growth factor A.

Intestinal bacteria metabolize dietary substances to produce bioactive postbiotics, among which some are recognized for their role in promoting host health. We here explored the postbiotic potential of two omega-3 α-linolenic acid-derived metabolites: trans-10-cis-15-octadecadienoic acid (t10,c15-18:2) and cis-9-cis-15-octadecadienoic acid (c9,c15-18:2). Dietary intake of lipids rich in omega-3 α-linolenic acid elevated levels of t10,c15-18:2 and c9,c15-18:2 in the serum and feces of mice, an effect dependent on the presence of intestinal bacteria. Notably, t10,c15-18:2 mitigated skin inflammation in mice that became hypersensitive after exposure to 2,4-dinitrofluorobenzene, an experimental model for allergic contact dermatitis. In particular, t10,c15-18:2-but not c9,c15-18:2-attenuated ear swelling and edema, characteristic symptoms of contact hypersensitivity. The anti-inflammatory effects of t10,c15-18:2 were due to its ability to suppress the release of vascular endothelial growth factor A from keratinocytes, thereby mitigating the enhanced vascular permeability induced by hapten stimulation. Our study identified retinoid X receptor as a functional receptor that mediates the downregulation of skin inflammation upon treatment with t10,c15-18:2. Our results suggest that t10,c15-18:2 holds promise as an omega-3 fatty acid-derived postbiotic with potential therapeutic implications for alleviating the skin edema seen in allergic contact dermatitis-induced inflammation.

Psychiatric Screening Measures in Behavioral Variant Frontotemporal Dementia.

Behavioral variant frontotemporal dementia (bvFTD) is sometimes misdiagnosed as a primary psychiatric disorder, such as major depressive disorder, bipolar disorder, an anxiety disorder, autism spectrum disorder (ASD), or attention-deficit hyperactivity disorder (ADHD). Nonspecialists often use screening measures for primary psychiatric disorders in early assessments of persons with bvFTD. The investigators aimed to evaluate the manifestations of bvFTD in surveys intended to screen for primary psychiatric disorders. Patients with bvFTD (N=27) presenting to an academic neurobehavior specialty clinic and their caregivers were provided questionnaire packets including the Mood Disorder Questionnaire (MDQ), the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 scale (GAD-7), the Adult ADHD Self-Report Scale, version 1.1, the Ritvo Autism and Asperger Diagnostic Scale, and the Neuropsychiatric Inventory Questionnaire. Established cutoff scores suggesting the presence of a primary psychiatric disorder were used to define a "positive" response. Individual questions from each screening questionnaire were examined for a more granular characterization of bvFTD. Overall, 15% of bvFTD patients screened positive for bipolar disorder, 54% screened positive for ADHD, and 89% screened positive for ASD. Hyperactivity or hypersensitivity symptoms were infrequently endorsed. In addition, 57% of respondents screened positive for depressive symptoms on the PHQ-9, and 43% screened positive for anxiety symptoms on the GAD-7. The use of cutoff scores on screening measures for primary psychiatric disorders resulted in potentially problematic positive screens of primary psychiatric disorders among persons with bvFTD. Identifying specific questions that distinguish between bvFTD and primary psychiatric disorders requires further study.