Olfactory function after mild traumatic brain injury in children-a longitudinal case control study.

The prevalence of posttraumatic olfactory dysfunction in children after mild traumatic brain injury ranges from 3 to 58%, with potential factors influencing this variation, including traumatic brain injury severity and assessment methods. This prospective longitudinal study examines the association between mild traumatic brain injury and olfactory dysfunction in children. Seventy-five pediatric patients with mild traumatic brain injury and an age-matched healthy control group were enrolled. Olfactory function was assessed using the Sniffin' Sticks battery, which focuses on olfactory threshold and odor identification. The study found that children with mild traumatic brain injury had impaired olfactory function compared with healthy controls, particularly in olfactory threshold scores. The prevalence of olfactory dysfunction in the patient group was 33% and persisted for 1 yr. No significant association was found between traumatic brain injury symptoms (e.g. amnesia, loss of consciousness) and olfactory dysfunction. The study highlights the importance of assessing olfactory function in children after mild traumatic brain injury, given its potential impact on daily life. Although most olfactory dysfunction appears transient, long-term follow-up is essential to fully understand the recovery process. The findings add valuable insights to the limited literature on this topic and urge the inclusion of olfactory assessments in the management of pediatric mild traumatic brain injury.

qU-Sniff - the development of a short version of the Universal "Sniffin' Sticks" test.

OBJECTIVES: Extensive olfactory testing is sparsely applied in pediatric patients in clinical routine especially because of its time taking nature. Therefore a 5-item odor identification test (quick "U-Sniff", "qU-Sniff") from the 12-item "U-Sniff" test was developed. METHODS: A total of 724 normosmic children between 6 and 17 years of age, divided in four age groups, were included in this retrospective study. Additionally, 17 children with congenital anosmia in the same age range were included. To calculate test-retest reliability 90 participants from the healthy group were tested twice. RESULTS: The five most correctly identified odors from the 12-item "U-Sniff" test were: coffee (98 %), peach (95 %), flower (90 %), fish (88 %) and onion (84 %). Normosmic participants scored 4.71 ± 0.62 points on the "qU-Sniff" test. A significant correlation between results of the 12-item and 5-item test (n = 724; rs = 0.580; p < 0.001) and a significant test-retest reliability (rs = 0.626, p < 0.001) were shown. For "qU-Sniff" validation a ROC analysis to distinguish between anosmic patients and healthy controls was conducted for each age group separately. AUCs were as followed: i) 0.963 ± 0.018, p < 0,001; ii) 0.978 ± 0.013, p < 0.001; iii) 0.992 ± 0.006, p < 0.001; iv) 0.994 ± 0.005, p < 0.001. The cut-off value to determine anosmic and normosmic participants was <4 points. CONCLUSION: With the "qU-Sniff" test, we present a short screening tool for clinical routine with <4 points as cut-off to initiate more detailed olfactory testing.

Normative data for olfactory threshold and odor identification in children and adolescents.

OBJECTIVE: Although previous studies have demonstrated the feasibility and validity of olfactory testing in children and adolescents using the "Sniffin' Sticks" odor threshold and "U-Sniff" odor identification test, normative data obtained in a large sample for these tests are missing. Aim of this study was therefore to obtain normative data of healthy children and adolescents for olfactory assessment. MATERIAL AND METHODS: Olfactory testing was conducted using the "Sniffin' Sticks" olfactory threshold (THR) and the 12-item "U-Sniff" odor identification (ID) test. The data were collected from 490 children and adolescents (234 girls, 257 boys) between the age of 6 and 17 years (mean age: 11.2 ±â€¯3.4 years). In line with previous studies, participants were divided into subgroups regarding their age: i) 6-8 years, ii) 9-11 years, iii) 12-14 years and iv) 15-17 years. RESULTS: All participants were able to perform the task. Neither sex nor age significantly influenced THR. Girls outperformed boys in ID. In addition, the youngest age group scored lower than the three other age groups on the "U-Sniff" odor identification test. Using the 10th percentile to distinguish normosmia from a reduced sense of smell the following values were obtained for the four age groups: i) THR 4.25 points, ID 7 points, ii) THR 5.0 points, ID 9 points, iii) THR 4.75 points, ID 10 points and iv) THR 5.5 points, ID 10 points. CONCLUSION: The present study provides normative data for olfactory assessment in children and adolescents using both an olfactory threshold and a suprathreshold test to distinguish between normosmia and a reduced sense of smell using the 10th percentile.

Synthesis and pharmacological characterization of benzenesulfonamides as dual species inhibitors of human and murine mPGES-1.

The microsomal prostaglandin E2 synthase 1 (mPGES-1) became a desirable target in recent years for the research of new anti-inflammatory drugs. Even though many potent inhibitors of human mPGES-1, tested in vitro assay systems, have been synthesized, they all failed in preclinical trials in rodent models of inflammation, due to the lack of activity on rodent enzyme. Within this work we want to present a new class of mPGES-1 inhibitors derived from a benzenesulfonamide scaffold with inhibitory potency on human and murine mPGES-1. Starting point with an IC50 of 13.8 µM on human mPGES-1 was compound 1 (4-{benzyl[(4-methoxyphenyl)methyl]sulfamoyl}benzoic acid; FR4), which was discovered by a virtual screening approach. Optimization during a structure-activity relationship (SAR) process leads to compound 28 (4-[(cyclohexylmethyl)[(4-phenylphenyl)methyl]sulfamoyl]benzoic acid) with an improved IC50 of 0.8 µM on human mPGES-1. For the most promising compounds a broad pharmacological characterization has been carried out to estimate their anti-inflammatory potential.

A novel class of dual mPGES-1/5-LO inhibitors based on the α-naphthyl pirinixic acid scaffold.

Dual inhibition of microsomal prostaglandin E(2) synthase-1 (mPGES-1) and 5-lipoxygenase (5-LO) represents a promising strategy in the development of novel anti-inflammatory drugs targeting the arachidonic acid cascade. Herein, a class of α-naphthyl pirinixic acids is characterized as dual mPGES-1/5-LO inhibitors. Systematic structural variation was focused on the lipophilic backbone of the scaffold and yielded detailed structure-activity relationships (SAR) with compound 16 (IC(50) mPGES-1=0.94 µM; IC(50) 5-LO=0.1 µM) showing the most favorable in vitro pharmacological profile.

Rational design of a pirinixic acid derivative that acts as subtype-selective PPARgamma modulator.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in glucose and lipid homeostasis. PPARgamma agonists are in clinical use for the treatment of type 2 diabetes. Lately, a new class of selective PPARgamma modulators (SPPARgammaMs) was developed, which are believed to show less side effects than full PPARgamma agonists. We have previously shown that alpha-substitution of pirinixic acid, a moderate agonist of PPARalpha and PPARgamma, leads to low micromolar active balanced dual agonists of PPARalpha and PPARgamma. Herein we present modifications of pirinixic acid leading to subtype-selective PPARgamma agonists and furthermore the development of a selective PPARgamma modulator guided by molecular docking studies.