Efficacy of a synbiotic in the management of adults with Attention-Deficit and Hyperactivity Disorder and/or Borderline Personality Disorder and high levels of irritability: Results from a multicenter, randomized, placebo-controlled, "basket" trial.

Irritability worsens prognosis and increases mortality in individuals with Attention-Deficit and Hyperactivity Disorder (ADHD) and/or Borderline Personality Disorder (BPD). However, treatment options are still insufficient. The aim of this randomized, double blind, placebo-controlled study was to investigate the superiority of a synbiotic over placebo in the management of adults with ADHD and/or BPD and high levels of irritability. The study was conducted between February 2019 and October 2020 at three European clinical centers located in Hungary, Spain and Germany. Included were patients aged 18-65 years old diagnosed with ADHD and/or BPD and high levels of irritability (i.e., an Affectivity Reactivity Index (ARI-S) ≥ 5, plus a Clinical Global Impression-Severity Scale (CGI-S) score ≥ 4). Subjects were randomized 1(synbiotic):1(placebo); the agent was administered each day, for 10 consecutive weeks. The primary outcome measure was end-of-treatment response (i.e., a reduction ≥ 30 % in the ARI-S total score compared to baseline, plus a Clinical Global Impression-Improvement (CGI-I) total score of < 3 (very much, or much improved) at week 10). Between-treatment differences in secondary outcomes, as well as safety were also investigated. Of the 231 included participants, 180 (90:90) were randomized and included in the intention-to-treat-analyses. Of these, 117 (65 %) were females, the mean age was 38 years, ADHD was diagnosed in 113 (63 %), BPD in 44 (24 %), both in 23 (13 %). The synbiotic was well tolerated. At week 10, patients allocated to the synbiotic experienced a significantly higher response rate compared to those allocated to placebo (OR: 0.2, 95 % CI:0.1 to 0.7; P = 0.01). These findings suggest that that (add-on) treatment with a synbiotic may be associated with a clinically meaningful improvement in irritability in, at least, a subgroup of adults with ADHD and/or BPD. A superiority of the synbiotic over placebo in the management of emotional dysregulation (-3.6, 95 % CI:-6.8 to -0.3; P = 0.03), emotional symptoms (-0.6, 95 % CI:-1.2 to -0.05; P = 0.03), inattention (-1.8, 95 % CI: -3.2 to -0.4; P = 0.01), functioning (-2.7, 95 % CI: -5.2 to -0.2; P = 0.03) and perceived stress levels (-0.6, 95 % CI: -1.2 to -0.05; P = 0.03) was also suggested. Higher baseline RANK-L protein levels were associated with a significantly lower response rate, but only in the synbiotic group (OR: 0.1, 95 % CI: -4.3 to - 0.3, P = 0.02). In the placebo group, higher IL-17A levels at baseline were significantly associated with a higher improvement in in particular, emotional dysregulation (P = 0.04), opening a door for new (targeted) drug intervention. However, larger prospective studies are warranted to confirm the findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03495375.

Human-induced pluripotent stem cell-derived ovarian support cell co-culture improves oocyte maturation in vitro after abbreviated gonadotropin stimulation.

STUDY QUESTION: Can in vitro maturation (IVM) and developmental competence of human oocytes be improved by co-culture with ovarian support cells (OSCs) derived from human-induced pluripotent stem cells (hiPSCs)? SUMMARY ANSWER: OSC-IVM significantly improves the rates of metaphase II (MII) formation and euploid Day 5 or 6 blastocyst formation, when compared to a commercially available IVM system. WHAT IS KNOWN ALREADY: IVM has historically shown highly variable performance in maturing oocytes and generating oocytes with strong developmental capacity, while limited studies have shown a positive benefit of primary granulosa cell co-culture for IVM. We recently reported the development of OSCs generated from hiPSCs that recapitulate dynamic ovarian function in vitro. STUDY DESIGN, SIZE, DURATION: The study was designed as a basic science study, using randomized sibling oocyte specimen allocation. Using pilot study data, a prospective sample size of 20 donors or at least 65 oocytes per condition were used for subsequent experiments. A total of 67 oocyte donors were recruited to undergo abbreviated gonadotropin stimulation with or without hCG triggers and retrieved cumulus-oocyte complexes (COCs) were allocated between the OSC-IVM or control conditions (fetal-like OSC (FOSC)-IVM or media-only IVM) in three independent experimental design formats. The total study duration was 1 April 2022 to 1 July 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Oocyte donors between the ages of 19 and 37 years were recruited for retrieval after informed consent, with assessment of anti-Mullerian hormone, antral follicle count, age, BMI and ovarian pathology used for inclusion and exclusion criteria. In experiment 1, 27 oocyte donors were recruited, in experiment 2, 23 oocyte donors were recruited, and in experiment 3, 17 oocyte donors and 3 sperm donors were recruited. The OSC-IVM culture condition was composed of 100 000 OSCs in suspension culture with hCG, recombinant FSH, androstenedione, and doxycycline supplementation. IVM controls lacked OSCs and contained either the same supplementation, FSH and hCG only (a commercial IVM control), or FOSCs with the same supplementation (Media control). Experiment 1 compared OSC-IVM, FOSC-IVM, and a Media control, while experiments 2 and 3 compared OSC-IVM and a commercial IVM control. Primary endpoints in the first two experiments were the MII formation (i.e. maturation) rate and morphological quality assessment. In the third experiment, the fertilization and embryo formation rates were assessed with genetic testing for aneuploidy and epigenetic quality in blastocysts. MAIN RESULTS AND THE ROLE OF CHANCE: We observed a statistically significant improvement (∼1.5×) in maturation outcomes for oocytes that underwent IVM with OSCs compared to control Media-IVM and FOSC-IVM in experiment 1. More specifically, the OSC-IVM group yielded a MII formation rate of 68% ± 6.83% SEM versus 46% ± 8.51% SEM in the Media control (P = 0.02592, unpaired t-test). FOSC-IVM yielded a 51% ± 9.23% SEM MII formation rate which did not significantly differ from the media control (P = 0.77 unpaired t-test). Additionally, OSC-IVM yielded a statistically significant ∼1.6× higher average MII formation rate at 68% ± 6.74% when compared to 43% ± 7.90% in the commercially available IVM control condition (P = 0.0349, paired t-test) in experiment 2. Oocyte morphological quality between OSC-IVM and the controls did not significantly differ. In experiment 3, OSC-IVM oocytes demonstrated a statistically significant improvement in Day 5 or 6 euploid blastocyst formation per COC compared to the commercial IVM control (25% ± 7.47% vs 11% ± 3.82%, P = 0.0349 logistic regression). Also in experiment 3, the OSC-treated oocytes generated blastocysts with similar global and germline differentially methylated region epigenetic profiles compared commercial IVM controls or blastocysts after either conventional ovarian stimulation. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: While the findings of this study are compelling, the cohort size remains limited and was powered on preliminary pilot studies, and the basic research nature of the study limits generalizability compared to randomized control trials. Additionally, use of hCG-triggered cycles results in a heterogenous oocyte cohort, and potential differences in the underlying maturation state of oocytes pre-IVM may limit or bias findings. Further research is needed to clarify and characterize the precise mechanism of action of the OSC-IVM system. Further research is also needed to establish whether these embryos are capable of implantation and further development, a key indication of their clinical utility. WIDER IMPLICATIONS OF THE FINDINGS: Together, these findings demonstrate a novel approach to IVM with broad applicability to modern ART practice. The controls used in this study are in line with and have produced similar to findings to those in the literature, and the outcome of this study supports findings from previous co-culture studies that found benefits of primary granulosa cells on IVM outcomes. The OSC-IVM system shows promise as a highly flexible IVM approach that can complement a broad range of stimulation styles and patient populations. Particularly for patients who cannot or prefer not to undergo conventional gonadotropin stimulation, OSC-IVM may present a viable path for obtaining developmentally competent, mature oocytes. STUDY FUNDING/COMPETING INTEREST(S): A.D.N., A.B.F., A.G., B.P., C.A., C.C.K., F.B., G.R., K.S.P., K.W., M.M., P.C., S.P., and M.-J.F.-G. are shareholders in the for-profit biotechnology company Gameto Inc. P.R.J.F. declares paid consultancy for Gameto Inc. P.C. also declares paid consultancy for the Scientific Advisory Board for Gameto Inc. D.H.M. has received consulting services from Granata Bio, Sanford Fertility and Reproductive Medicine, Gameto, and Buffalo IVF, and travel support from the Upper Egypt Assisted Reproduction Society. C.C.K., S.P., M.M., A.G., B.P., K.S.P., G.R., and A.D.N. are listed on a patent covering the use of OSCs for IVM: U.S. Provisional Patent Application No. 63/492,210. Additionally, C.C.K. and K.W. are listed on three patents covering the use of OSCs for IVM: U.S. Patent Application No. 17/846,725, U.S Patent Application No. 17/846,845, and International Patent Application No.: PCT/US2023/026012. C.C.K., M.P.S., and P.C. additionally are listed on three patents for the transcription factor-directed production of granulosa-like cells from stem cells: International Patent Application No.: PCT/US2023/065140, U.S. Provisional Application No. 63/326,640, and U.S. Provisional Application No. 63/444,108. The remaining authors have no conflicts of interest to declare.

High-fat and combined high-fat-high-fructose diets impair episodic-like memory and decrease glutamate and glutamine in the hippocampus of adult mice.

BACKGROUND: Diet-induced obesity is associated with premature cognitive decline. Elevated consumption of fats and sugars in humans and rodents has been associated with deficits in recognition memory, which is modulated by the hippocampus. Alterations in excitatory and inhibitory neurotransmitters in this area have been observed after hypercaloric diets, but the effects on episodic-like memory are not conclusive. OBJECTIVE: To investigate the effects of hypercaloric diets on memory and their relationship with γ-aminobutyric acid (GABA), glutamate and glutamine and their genetic expression in the hippocampus. DESIGN: A control diet (CD), a high-fat diet (HFD) and a combined high-fat-high-fructose diet (HFFrD) were administered to 30 C57BL/6 adult mice for 10 weeks. The discrimination indexes and exploration time of the novel object recognition (NOR) and novel object location (NOL) tasks were evaluated and GABA, glutamate and glutamine concentrations and their genetic expression were obtained from the hippocampus. RESULTS: The HFFrD induced lower discrimination indexes, decreased exploration time in the recognition memory tasks, and lowered the concentrations of glutamate and glutamine, and HFD increased their expression in the hippocampus. CONCLUSIONS: These findings suggest that a possible adaptative long-term mechanism in the hippocampal neurotransmitters, and this possibility may underlie the episodic-like memory deficits in mice fed HFD and HFFrD.

Emergency department crowding negatively influences outcomes for adults presenting with asthma: a population-based retrospective cohort study.

BACKGROUND: Access to emergency department (ED) services is important for patients with acute asthma; however, ED crowding may impact the quality of care and compromise outcomes. We examine the association between ED crowding metrics and individual patient outcomes for adults presenting with asthma. METHODS: This population-based retrospective cohort study extracted all ED presentations made by patients aged 18 to 55 years to 18 high-volume EDs in Alberta from April 2014 to March 2019. Physician initial assessment (PIA) time and ED length of stay (LOS) for discharged and admitted patients were calculated. Other metrics and patient outcomes were also obtained. Linear and generalized linear models were fit for continuous and categorical outcomes. Cox proportional hazards models were used for time-to-event outcomes. RESULTS: There were 17,724 ED presentations by 12,569 adults. The median age was 33 years, and females (58.7%) made more presentations. ED crowding affected the PIA time for all triage groups. For the high acuity group (Canadian Triage and Acuity Scale [CTAS] 1/2), 1 h increase in median facility-specific PIA was associated with 26 min (95%CI: 24,28) increase; for the moderate acuity (CTAS 3) and low acuity (CTAS 4/5) groups, the individual-level PIA increased by 54 min (95%CI: 53,55) and 61 min (95%CI: 59,63), respectively adjusted by other predictors. Increases in facility PIA resulted in increase in odds of admissions for the high acuity group and increase odds of left without completion of care for the moderate and low acuity groups. CONCLUSION: The care provided for patients from all triage groups was impacted when EDs experienced crowding. Effective interventions are needed to mitigate ED crowding and improve care and outcomes for this important patient group.

Slow electroencephalographic oscillations and behavioral measures as predictors of high executive processing in early postmenopausal females: A discriminant analysis approach.

Decline in cognitive function is frequent in early postmenopause. There are postmenopausal females who show high performance while others display low performance in executive function, modulated by the prefrontal cortex. These differences have led to confusing and inconclusive results, which have not been explained entirely by the decline in estrogens, which affect the prefrontal cortex functions. An analysis of brain function and the application of a discriminant analysis can help to clarify the deficits in executive function shown by some postmenopausal females. The objective was to examine electroencephalographic recording during the performance of an executive function test in early postmenopausal females, ten with a high level of performance and ten with a low level of performance. Absolute power of delta, theta, alpha1, alpha2, beta1 and beta2 and the numbers of completed categories, trials, perseverative errors and overall errors were submitted to stepwise discriminant analysis to identify predictor variables. Four predictors emerged as significant of group membership based on cognitive performance, with the high-performance group characterized by more completed categories, more delta power, less theta power and more alpha1 power. These findings suggest that postmenopausal females classified in the high-performance group displayed appropriate temporary activation in slow oscillations during executive processing.

Validity and reliability of the kiddie schedule for affective disorders and schizophrenia present and lifetime version DSM-5 (K-SADS-PL-5) Spanish version.

BACKGROUND: There are various language adaptations of the Schedule for Affective Disorders and Schizophrenia for School Age Children Present and Lifetime Version (K-SADS-PL). In order to comply with the changes in DSM classification, the Spanish edition of the interview was in need of update and evaluation. METHODS: K-SADS-PL was adapted to correspond to DSM-5 categories. All clinicians received training, and a 90% agreement was reached. Patients and their parents or guardians were interviewed and videotaped, and the videos were exchanged between raters. Factor analysis was performed and inter-rater reliability was calculated only in the case of diagnoses in which there were more than five patients. RESULTS: A total of 74 subjects were included. The Factor Analysis yielded six factors (Depressive, Stress Hyperarousal, Disruptive Behavioral, Irritable Explosive, Obsessive Repetitive and Encopresis), representing 72% of the variance. Kappa values for inter-rater agreement were larger than 0.7 for over half of the disorders. CONCLUSIONS: The factor structure of diagnoses, made with the instrument was found to correspond to the DSM-5 disorder organization. The instrument showed good construct validity and inter-rater reliability, which makes it a useful tool for clinical research studies in children and adolescents.

Inflammatory biotype of ADHD is linked to chronic stress: a data-driven analysis of the inflammatory proteome.

The association between Attention Deficit Hyperactivity Disorder (ADHD) and low-grade inflammation has been explored in children but rarely in adults. Inflammation is characteristic of some, but not all, patients with ADHD and might be influenced by ADHD medication but also lifestyle factors including nutrition, smoking, and stress. It is also still unclear if any specific symptoms are related to inflammation. Therefore, we assessed 96 inflammatory proteins in a deeply phenotyped cohort of 126 adult ADHD participants with a stable medication status using OLINK technology. A data-based, unsupervised hierarchical clustering method could identify two distinct biotypes within the 126 ADHD participants based on their inflammatory profile: a higher inflammatory potential (HIP) and a lower inflammatory protein potential (LIP) group. Biological processes that differed strongest between groups were related to the NF-κB pathway, chemokine signaling, IL-17 signaling, metabolic alterations, and chemokine attraction. A comparison of sample characteristics revealed that the HIP group was more likely to have higher levels of chronic stress (p < 0.001), a higher clinical global impression scale score (p = 0.030), and a higher risk for suicide (p = 0.032). Medication status did not influence protein levels significantly (p ≥ 0.074), but psychotropic co-medication (p ≤ 0.009) did. In conclusion, our data suggest the presence of two distinct biotypes in adults with ADHD. Higher levels of inflammatory proteins in ADHD are linked to higher levels of chronic perceived stress in a linear fashion. Further research on inflammation in adults with ADHD should take stress levels into account.

Emergency department crowding negatively influences outcomes for adults presenting for chronic obstructive pulmonary disease.

OBJECTIVES: Emergency department (ED) crowding leads to poor outcomes. Patients with respiratory conditions like chronic obstructive pulmonary disease (COPD) are especially vulnerable to crowding-related delays in care. We aimed to assess the associations of ED crowding metrics with outcomes for patients presenting with COPD. METHODS: We conducted a population-based cohort study of adult patients presenting with a diagnosis of COPD to 18 high-volume EDs between 2014 and 2019 in Alberta, Canada. Administrative databases provided date and time data on key stages of the presentation including physician initial assessment and disposition decision. Crowding metrics were calculated using facility-specific median physician initial assessment and length of stay. Patient presentations were grouped by acuity and mixed-effects regression models were fit to adjust for the clustering at the facility level. RESULTS: There were 49,085 presentations for COPD made by 25,734 patients (median age = 73 years). A 1-h increase in the physician initial assessment metric was associated with an increase in physician initial assessment for COPD patients by 23, 53, and 59 min for the high, moderate, and low acuity groups, respectively, adjusted for other predictors. For the low acuity group, this metric was associated with an increased length of stay of 73 min for admitted individuals. Similarly, an increase in the length of stay metric was also associated with an increased likelihood of being admitted for all acuity groups. CONCLUSIONS: For patients with COPD, ED crowding results in delays in assessment increased length of stay, and increased proportion of patients admitted. These results suggest that ED crowding mitigation efforts to provide timely care for patients with COPD are urgently needed. TRIAL REGISTRATION: N/A.

RéSUMé: OBJECTIFS: L'encombrement des services d'urgence entraîne de mauvais résultats. Les patients souffrant de maladies respiratoires telles que la maladie pulmonaire obstructive chronique (MPOC) sont particulièrement vulnérables aux retards de soins liés à l'encombrement. Notre avons cherché à évaluer les associations entre les paramètres d'encombrement des services d'urgence et les résultats pour les patients présentant une MPOC. MéTHODES: Nous avons mené une étude de cohorte basée sur la population de patients adultes se présentant avec un diagnostic de MPOC dans dix-huit services d'urgence à haut volume entre 2014 et 2019 en Alberta, au Canada. Les bases de données administratives ont fourni des données sur la date et l'heure des principales étapes de la présentation, y compris l'évaluation initiale par le médecin et la décision de sortie. Les mesures d'encombrement ont été calculées à partir de l'évaluation initiale médiane du médecin et de la durée du séjour propres à l'établissement. Les présentations des patients ont été regroupées par gravité et des modèles de régression à effets mixtes ont été ajustés pour tenir compte du regroupement au niveau de l'établissement. RéSULTATS: Il y a eu 49 085 présentations pour la MPOC effectuées par 25 734 patients (âge médian = 73 ans). Une augmentation d'une heure de l'évaluation initiale par le médecin était associée à une augmentation de l'évaluation initiale par le médecin pour les patients atteints de MPOC de 23, 53 et 59 min pour les groupes de gravité élevée, modérée et faible, respectivement, après ajustement pour d'autres facteurs prédictifs. Pour le groupe de faible gravité, ce paramètre était associé à une augmentation de la durée de séjour de 73 min pour les personnes admises. De même, une augmentation de la durée du séjour était également associée à une probabilité accrue d'admission pour tous les groupes de gravité. CONCLUSIONS: Pour les patients atteints de MPOC, l'encombrement des urgences entraîne des retards dans l'évaluation, une augmentation de la durée du séjour et une augmentation de la proportion de patients admis. Ces résultats suggèrent qu'il est urgent d'atténuer l'encombrement des urgences afin de fournir des soins en temps opportun aux patients atteints de MPOC. ENREGISTREMENT DE L'ESSAI: N/A.

Children's Anxiety Levels and Their Perspectives on Dental Experiences in Students' Clinical Evaluation.

Aim: The purpose of this study is to present a framework for the potential implementation of children's anxiety levels and perspectives of their experiences receiving treatment from dental students through interviews and drawing into the clinical assessment of dental students. Materials and methods: A total of 51 patients between the ages of 5 and 8 years were included in the study. Pulp therapy and/or restorative treatment was performed during the first therapeutic session for all participants. Children were asked to draw about themselves at the dentist's and then verbally explain their drawings. Drawings were analyzed using Child Drawing: Hospital (CD: H) to determine the child's anxiety score. Interviews were analyzed using thematic analysis to establish the factors contributing to the patient having a positive/negative experience. The relationships between the children's level of anxiety and their experience were analyzed using correlation and regression analyses against the student clinical assessment data. Results: Most children in the study exhibited average levels of anxiety and had an overall positive perception of the dentist. The correlation and regression analyses determined that when children presented higher levels of anxiety, the students received statistically significant higher scores in evidence-informed practice (EIP), skills, and their tolerance for error during procedures. No other rubric item was related to the children's anxiety or whether their experience was positive/negative. Conclusion: Although this study provided a framework for exploring children's anxiety levels and perspectives of their experiences in teaching clinical settings, more research is needed to refine the method for student evaluation. Clinical significance: This study will enable dental students to meet the needs of child patients, which consequently increases treatment motivation and adherence to dental services as well as reduces the likelihood of patient anxiety and improves patient self-care skills over time. How to cite this article: Ortiz S, Yoon M, Gibson M, et al. Children's Anxiety Levels and Their Perspectives on Dental Experiences in Students' Clinical Evaluation. Int J Clin Pediatr Dent 2023;16(S-2):S206-S212.

Comparison of the effects of target-controlled infusion-remifentanil/midazolam and manual fentanyl/midazolam administration on patient parameters in dental procedures.

Background: Moderate sedation is an integral part of dental care delivery. Target-controlled infusion (TCI) has the potential to improve patient safety and outcome. We compared the effects of using TCI to administer remifentanil/manual bolus midazolam with manual bolus fentanyl/midazolam administration on patient safety parameters, drug administration times, and patient recovery times. Methods: In this retrospective chart review, records of patients who underwent moderate intravenous sedation over 12 months in a private dental clinic were assessed. Patient indicators (pre-, intra-, and post-procedure noninvasive systolic and diastolic blood pressure, respiration, and heart rate) were compared using independent t-test analysis. Patient recovery time, procedure length, and midazolam dosage required were also compared between the two groups. Results: Eighty-five patient charts were included in the final analysis: 47 received TCI-remifentanil/midazolam sedation, and 38 received manual fentanyl/midazolam sedation. Among the physiological parameters, diastolic blood pressure showed slightly higher changes in the fentanyl group (P = 0.049), respiratory rate changes showed higher changes in the fentanyl group (P = 0.032), and the average EtCO2 was slightly higher in the remifentanil group (P = 0.041). There was no significant difference in the minimum SpO2 levels and average procedure length between the fentanyl and remifentanil TCI pump groups (P > 0.05). However, a significant difference was observed in the time required for discharge from the chair (P = 0.048), indicating that patients who received remifentanil required less time for discharge from the chair than those who received fentanyl. The dosage of midazolam used in the fentanyl group was 0.487 mg more than that in the remifentanil group; however, the difference was not significant (P > 0.05). Conclusion: The combination of TCI administered remifentanil combined with manual administered midazolam has the potential to shorten the recovery time and reduce respiration rate changes when compared to manual administration of fentanyl/midazolam. This is possibly due to either the lower midazolam dosage required with TCI remifentanil administration or achieving a stable, steady-state low dose remifentanil concentration for the duration of the procedure.

Dietary intake of micro- and macronutrients is associated with deficits in executive functioning in young women with high adiposity.

OBJECTIVES: Deficits in cognitive functions dependent on the prefrontal cortex related to the dietary intake of nutrients and adiposity in young individuals are not well known. The objective of this study was to examine the effects of high adiposity on executive functioning and their relationship with dietary intake of macro- and micronutrients in young women. METHODS: Ninety-five young women were categorized based on body fat percentage. The study included 42 women with normal adiposity and 53 women with high adiposity. Executive functions, sustained attention, selective attention, category formation, cognitive flexibility, and verbal fluency test scores were obtained to assess executive functioning. Dietary intake of macro- and micronutrients was measured using three 24-h recalls, and correlated with the test scores. RESULTS: The high-adiposity group was characterized by deficits in executive function, category formation and cognitive flexibility, poor sustained and selective attention, and less verbal fluency. Executive functions were negatively correlated with saturated fat and positively correlated with cholesterol and carbohydrates. Category formation was negatively correlated with saturated fat and vitamin E. Sustained attention was positively correlated with lipids, carbohydrates, and cholesterol. Long reaction times in the selective attention test were positively correlated with unsaturated fat and negatively correlated with vitamin C. Cognitive flexibility test scores were negatively correlated with vitamin E. Cholesterol, vitamin C, and vitamin E were predictors of executive functioning in the high-adiposity group. CONCLUSIONS: These findings suggest that impairments in executive functioning may predispose young women to overconsumption of unhealthy nutrients that consequently induces obesity.

Dental Students' Knowledge, Confidence, Ability, and Self-Reported Difficulties in Periodontal Education: A Mixed Method Pilot Study.

Evidence on periodontal education areas in which students have difficulties and their factors are limited. In this study, third- and fourth-year dental students' knowledge was assessed as well as their confidence and ability in five periodontal educational areas using a mixed-method approach. A survey was used to collect data related to history-taking, medical examination, diagnosis, treatment planning, and follow-up. Student answers were compared to the consensual answers of an expert panel using the cosine-similarity index (CSI). Descriptive statistics assessed confidence and ability for diagnosis. Semi-structured individual interviews were used to collect data on reported reasons for difficulties in periodontal education. A content analysis was employed to analyze the interview data. Eighteen third- and fourth-year dental students completed the survey and eleven were interviewed. Students' knowledge was adequate regarding diagnosis and treatment planning. Third-year students' median CSI were 0.93 and 0.89, respectively. Fourth-year students' median CSI were 0.9 and 0.93, respectively. Students felt confident in history-taking and examination but lacked confidence and ability in diagnosis and treatment planning. Reported reasons for difficulties in periodontal education were linked to both preclinical and clinical pedagogical issues. Further improvements in preclinical and clinical periodontal education are needed to address students' lack of knowledge, confidence, and skills in key periodontal areas.

Quantifying the intensity of adverse events with ibuprofen and oxycodone: an observational cohort study.

OBJECTIVE: To quantify the frequency and intensity of adverse events (AEs), commonly known as side effects, experienced by children receiving either ibuprofen or oxycodone for pain management following an acute fracture. Secondary objectives were to quantify functional outcome impairment and describe demographic and clinical characteristics associated with AEs. DESIGN: Observational cohort study. SETTING: Paediatric emergency department. PATIENTS: Patients (n=240) aged 4-16 years diagnosed with an acute fracture. INTERVENTION: Prescribed either ibuprofen (n=179) or oxycodone (n=61) for pain. MAIN OUTCOME MEASURES: Families were called for the first 3 days after discharge to report the presence and intensity of AEs and their child's functional outcomes (ability to eat, sleep, play or attend school). RESULTS: On day 1, children using oxycodone were more likely to report any AE (χ2 1=13.5, p<0.001), nausea (χ2 1=17.0, p<0.001), vomiting (χ2 1=11.2, p<0.001), drowsiness (χ2 1=13.7,p<0.001), constipation (χ2 1=8.9, p=0.003) and dizziness (χ2 1=19.1, p<0.001), compared with those using ibuprofen. Children receiving oxycodone reported greater severity of abdominal pain (oxycodone: mean 5.4 SD 3.1; ibuprofen mean 2.5 SD 1.4, F1 13=6.5, p=0.02) on day 1 and worse intensity of constipation (oxycodone: mean 4.9 SD 2.1; ibuprofen mean 3.2 SD 2.2, F1 33=4.5, p=0.04) over all 3 days. Use of oxycodone was associated with an increased odds of experiencing an AE on day 1 (OR=1.31 (95% CI 1.13 to 1.52)). Higher pain scores (OR=1.50 (95% CI 1.12 to 2.01)), lower extremity fracture (OR=1.25 (95% CI 1.07 to 1.47)) and undergoing ED sedation (OR=1.16 (95% CI 1.01 to 1.34)) were associated with missing school. Higher pain scores (OR=1.50 (95% CI 1.14 to 1.97)) and lower extremity fractures (OR=1.23 (95% CI 1.07 to 1.43)) were also associated with less play. CONCLUSIONS: Oxycodone is associated with more frequent AEs overall, higher intensity gastrointestinal AEs and greater functional limitations compared with ibuprofen. Lower extremity fractures cause more functional limitations than upper extremity fractures. Clinicians should consider these differences when providing fracture pain care for children.

Spatial epidemiology of Leptospira sp. exposure in bovines from Veracruz, México.

Bovine leptospirosis is a bacterial disease that affects cattle herds, causing economic losses due to reproductive problems which require expensive treatments. The main source of transmission for cattle is still uncertain, but rodents and bats can play an important role in the transmission cycle by being maintenance hosts for the pathogenic species of the bacterium and spreading it through urine. In this study, we characterize possible risk areas for bovine leptospirosis exposure in the state of Veracruz, Mexico, based on the geographical distribution of flying (bats) and terrestrial (rodents and opossums) wild hosts of Leptospira sp. reported in Mexico, in addition to climate, geography, soil characteristics, land use and human activities (environmental variables). We used a generalized linear regression model to understand the association between the frequency of anti-Leptospira sp. antibodies (a proxy of exposure) in cattle herds exposed to Leptospira, the favourability of wild hosts of Leptospira as well as the environmental variables. The parameterized model explained 12.3% of the variance. The frequency of anti-Leptospira sp. antibodies exposure in cattle herds was associated with elevation, geographic longitude, pH of the soil surface and environmental favourability for the presence of rodents, opossums and bats. The variation in exposure was mainly explained by a longitudinal gradient (6.4% of the variance) and the favourability-based indices for wild hosts (9.6% of the variance). Describing the possible risks for exposure to Leptospira in an important and neglected livestock geographical region, we provide valuable information for the selection of areas for diagnosis and prevention of this relevant disease.

ICD-11 Guidelines for Mental and Behavioral Disorders of Children and Adolescents: Reliability and Clinical Utility.

OBJECTIVE: ICD-11 clinical guidelines for mental and behavioral disorders must be tested in clinical settings to guarantee their usefulness worldwide. The purpose of this study was to evaluate interrater reliability and clinical utility of the ICD-11 guidelines for children and adolescents in assessing and diagnosing mood, anxiety, and fear-related disorders; attention-deficit hyperactivity disorder (ADHD); and disruptive behavioral disorder (DBD). METHODS: Children and adolescents ages 6-17 from two specialized settings in Mexico City were interviewed. Each was interviewed by a pair of psychiatrists (interviewer and observer), who independently codified established diagnoses and evaluated the clinical utility of the guidelines with each participant. Kappa values were calculated to determine the level of general diagnostic correlation between the two clinicians. RESULTS: A total of 25 psychiatrists evaluated 52 children and adolescents. Kappa values between clinicians ranged from 0.46 to 0.53 for mood, anxiety, and fear-related disorders and for ADHD; the kappa value was 0.81 for DBD guidelines. Over 80% of psychiatrists reported that the guidelines, qualifiers, and descriptions of developmental presentations were quite useful. CONCLUSIONS: ICD-11 guidelines for mental and behavioral disorders of children and adolescents demonstrated mostly moderate interrater reliability and strong interrater reliability in the case of DBD. A large proportion of clinicians regarded the guidelines as quite useful clinical tools.

Evaluating Classification Consistency of Oral Lesion Images for Use in an Image Classification Teaching Tool.

A web-based image classification tool (DiLearn) was developed to facilitate active learning in the oral health profession. Students engage with oral lesion images using swipe gestures to classify each image into pre-determined categories (e.g., left for refer and right for no intervention). To assemble the training modules and to provide feedback to students, DiLearn requires each oral lesion image to be classified, with various features displayed in the image. The collection of accurate meta-information is a crucial step for enabling the self-directed active learning approach taken in DiLearn. The purpose of this study is to evaluate the classification consistency of features in oral lesion images by experts and students for use in the learning tool. Twenty oral lesion images from DiLearn's image bank were classified by three oral lesion experts and two senior dental hygiene students using the same rubric containing eight features. Classification agreement among and between raters were evaluated using Fleiss' and Cohen's Kappa. Classification agreement among the three experts ranged from identical (Fleiss' Kappa = 1) for "clinical action", to slight agreement for "border regularity" (Fleiss' Kappa = 0.136), with the majority of categories having fair to moderate agreement (Fleiss' Kappa = 0.332-0.545). Inclusion of the two student raters with the experts yielded fair to moderate overall classification agreement (Fleiss' Kappa = 0.224-0.554), with the exception of "morphology". The feature of clinical action could be accurately classified, while other anatomical features indirectly related to diagnosis had a lower classification consistency. The findings suggest that one oral lesion expert or two student raters can provide fairly consistent meta-information for selected categories of features implicated in the creation of image classification tasks in DiLearn.

Effect of Detailed OSCE Score Reporting on Learning and Anxiety in Medical School.

INTRODUCTION: There is growing literature on increasing feedback from Objective Structured Clinical Examinations (OSCEs) and one approach is a score report. The purpose of this study was to implement and evaluate a score report for a second and fourth-year medical school OSCE. METHODS: We developed an electronic OSCE score report that displayed comments and performance by domain within and across stations (checklist items and rating scales were tagged to each domain). Our initial pilot released the score report after pass/fail decisions but subsequent iterations released the score report the same day as the exam. Our evaluation approach included both student surveys and focus groups. RESULTS: Students felt the OSCE score report was accurate, identified strengths and weaknesses, and would likely cause them to take future action, with second-year students more likely to act on the report than fourth year students. The thematic analysis revealed barriers and enablers to utilizing feedback as well as the power of the score report to reduce anxiety. CONCLUSIONS: Our OSCE score report was simple to develop and implement the same day as an OSCE with an overall positive response from students with respect to accuracy and ability to use the information for future learning.

Deficiency in the Essential Amino Acids l-Isoleucine, l-Leucine and l-Histidine and Clinical Measures as Predictors of Moderate Depression in Elderly Women: A Discriminant Analysis Study.

Increases in depression are common in some elderly women. Elderly women often show moderate depressive symptoms, while others display minimal depressive symptoms. These discrepancies have produced contradictory and inconclusive outcomes, which have not been explained entirely by deficits in neurotransmitter precursors. Deficiency in some amino acids have been implicated in major depression, but its role in non-clinical elderly women is not well known. An analysis of essential amino acids, depression and the use of discriminant analysis can help to clarify the variation in depressive symptoms exhibited by some elderly women. The aim was to investigate the relationship of essential amino acids with affective, cognitive and comorbidity measures in elderly women without major depression nor severe mood disorders or psychosis, specifically thirty-six with moderate depressive symptoms and seventy-one with minimal depressive symptoms. The plasma concentrations of nineteen amino acids, Beck Depression Inventory (BDI) scores, Geriatric Depression Scale (GDS) scores, global cognitive scores and comorbidities were submitted to stepwise discriminant analysis to identify predictor variables. Seven predictors arose as important for belong to the group based on amino acid concentrations, with the moderate depressive symptoms group characterized by higher BDI, GDS and cognitive scores; fewer comorbidities; and lower levels of l-histidine, l-isoleucine and l-leucine. These findings suggest that elderly women classified as having moderate depressive symptoms displayed a deficiency in essential amino acids involved in metabolism, protein synthesis, inflammation and neurotransmission.

Gut microbiota signature in treatment-naïve attention-deficit/hyperactivity disorder.

Compelling evidence supports alterations in gut microbial diversity, bacterial composition, and/or relative abundance of several bacterial taxa in attention-deficit/hyperactivity disorder (ADHD). However, findings for ADHD are inconsistent among studies, and specific gut microbiome signatures for the disorder remain unknown. Given that previous studies have mainly focused on the pediatric form of the disorder and involved small sample sizes, we conducted the largest study to date to compare the gastrointestinal microbiome composition in 100 medication-naïve adults with ADHD and 100 sex-matched healthy controls. We found evidence that ADHD subjects have differences in the relative abundance of several microbial taxa. At the family level, our data support a lower relative abundance of Gracilibacteraceae and higher levels of Selenomonadaceae and Veillonellaceae in adults with ADHD. In addition, the ADHD group showed higher levels of Dialister and Megamonas and lower abundance of Anaerotaenia and Gracilibacter at the genus level. All four selected genera explained 15% of the variance of ADHD, and this microbial signature achieved an overall sensitivity of 74% and a specificity of 71% for distinguishing between ADHD patients and healthy controls. We also tested whether the selected genera correlate with age, body mass index (BMI), or scores of the ADHD rating scale but found no evidence of correlation between genera relative abundance and any of the selected traits. These results are in line with recent studies supporting gut microbiome alterations in neurodevelopment disorders, but further studies are needed to elucidate the role of the gut microbiota on the ADHD across the lifespan and its contribution to the persistence of the disorder from childhood to adulthood.

Executive functions and selective attention are favored in middle-aged healthy women carriers of the Val/Val genotype of the catechol-o-methyltransferase gene: a behavioral genetic study.

BACKGROUND: Cognitive deficits such as poor memory, the inability to concentrate, deficits in abstract reasoning, attention and set-shifting flexibility have been reported in middle-aged women. It has been suggested that cognitive decline may be due to several factors which include hormonal changes, individual differences, normal processes of aging and age-related changes in dopaminergic neurotransmission. Catechol-O-methyltransferase (COMT), a common functional polymorphism, has been related to executive performance in young healthy volunteers, old subjects and schizophrenia patients. The effect of this polymorphism on cognitive function in middle-aged healthy women is not well known. The aim of the current study was to investigate whether measures of executive function, sustained attention, selective attention and verbal fluency would be different depending on the COMT genotype and task demand. METHOD: We genotyped 74 middle-aged healthy women (48 to 65 years old) for the COMT Val158Met polymorphism. We analyzed the effects of this polymorphism on executive functions (Wisconsin Card Sorting Test), selective attention (Stroop test), sustained attention (Continuous Performance Test) and word generation (Verbal Fluency test), which are cognitive functions that involve the frontal lobe. RESULTS: There were 27 women with the Val/Val COMT genotype, 15 with the Met/Met genotype, and 32 with the Val/Met genotype. Women carriers of the Val/Val genotype performed better in executive functions, as indicated by a lower number of errors committed in comparison with the Met/Met or Val/Met groups. The correct responses on selective attention were higher in the Val/Val group, and the number of errors committed was higher in the Met/Met group during the incongruence trial in comparison with the Val/Val group. Performance on sustained attention and the number of words generated did not show significant differences between the three genotypes. CONCLUSION: These findings indicate that middle-aged women carriers of the Val158 allele, associated with high-activity COMT, showed significant advantage over Met allele in executive processes and cognitive flexibility. These results may help to explain, at least in part, individual differences in cognitive decline in middle-aged women with dopamine-related genes.