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Sleep and circadian rhythms are observed broadly throughout animal phyla and influence neural plasticity and cognitive function. However, the few phylogenetically conserved cellular and molecular pathways that are implicated in these processes are largely focused on neuronal cells. Research on these topics has traditionally segregated sleep homeostatic behavior from circadian rest-activity rhythms. Here we posit an alternative perspective, whereby mechanisms underlying the integration of sleep and circadian rhythms that affect behavioral state, plasticity, and cognition reside within glial cells. The brain-type fatty acid binding protein, FABP7, is part of a larger family of lipid chaperone proteins that regulate the subcellular trafficking of fatty acids for a wide range of cellular functions, including gene expression, growth, survival, inflammation, and metabolism. FABP7 is enriched in glial cells of the central nervous system and has been shown to be a clock-controlled gene implicated in sleep/wake regulation and cognitive processing. FABP7 is known to affect gene transcription, cellular outgrowth, and its subcellular localization in the fine perisynaptic astrocytic processes (PAPs) varies based on time-of-day. Future studies determining the effects of FABP7 on behavioral state- and circadian-dependent plasticity and cognitive processes, in addition to functional consequences on cellular and molecular mechanisms related to neural-glial interactions, lipid storage, and blood brain barrier integrity will be important for our knowledge of basic sleep function. Given the comorbidity of sleep disturbance with neurological disorders, these studies will also be important for our understanding of the etiology and pathophysiology of how these diseases affect or are affected by sleep.

Fatty acid binding proteins (FABPs) are a family of intracellular lipid chaperone proteins known to play critical roles in the regulation of fatty acid uptake and transport as well as gene expression. Brain-type fatty acid binding protein (FABP7) is enriched in astrocytes and has been implicated in sleep/wake regulation and neurodegenerative diseases; however, the precise mechanisms underlying the role of FABP7 in these biological processes remain unclear. FABP7 binds to both arachidonic acid (AA) and docosahexaenoic acid (DHA), resulting in discrete physiological responses. Here, we propose a dichotomous role for FABP7 in which ligand type determines the subcellular translocation of fatty acids, either promoting wakefulness aligned with Alzheimer’s pathogenesis or promoting sleep with concomitant activation of anti-inflammatory pathways and neuroprotection. We hypothesize that FABP7-mediated translocation of AA to the endoplasmic reticulum of astrocytes increases astrogliosis, impedes glutamatergic uptake, and enhances wakefulness and inflammatory pathways via COX-2 dependent generation of pro-inflammatory prostaglandins. Conversely, we propose that FABP7-mediated translocation of DHA to the nucleus stabilizes astrocyte-neuron lactate shuttle dynamics, preserves glutamatergic uptake, and promotes sleep by activating anti-inflammatory pathways through the peroxisome proliferator-activated receptor-γ transcriptional cascade. Importantly, this model generates several testable hypotheses applicable to other neurodegenerative diseases, including amyotrophic lateral sclerosis and Parkinson’s disease.

The astrocyte brain-type fatty-acid binding protein (Fabp7) circadian gene expression is synchronized in the same temporal phase throughout mammalian brain. Cellular and molecular mechanisms that contribute to this coordinated expression are not completely understood, but likely involve the nuclear receptor Rev-erbα (NR1D1), a transcriptional repressor. We performed ChIP-seq on ventral tegmental area (VTA) and identified gene targets of Rev-erbα, including Fabp7. We confirmed that Rev-erbα binds to the Fabp7 promoter in multiple brain areas, including hippocampus, hypothalamus, and VTA, and showed that Fabp7 gene expression is upregulated in Rev-erbα knock-out mice. Compared to Fabp7 mRNA levels, Fabp3 and Fabp5 mRNA were unaffected by Rev-erbα depletion in hippocampus, suggesting that these effects are specific to Fabp7. To determine whether these effects of Rev-erbα depletion occur broadly throughout the brain, we also evaluated Fabp mRNA expression levels in multiple brain areas, including cerebellum, cortex, hypothalamus, striatum, and VTA in Rev-erbα knock-out mice. While small but significant changes in Fabp5 mRNA expression exist in some of these areas, the magnitude of these effects are minimal to that of Fabp7 mRNA expression, which was over 6-fold across all brain regions. These studies suggest that Rev-erbα is a transcriptional repressor of Fabp7 gene expression throughout mammalian brain.

Parkinson’s Disease (PD) is the most common movement disorder, and the strongest genetic risk factor for PD is mutations in the glucocerebrosidase gene (GBA). Mutations in GBA also lead to the development of Gaucher Disease (GD), the most common type of lysosomal storage disorder. Current therapeutic approaches fail to address neurological GD symptoms. Therefore, identifying therapeutic strategies that improve the phenotypic traits associated with GD/PD in animal models may provide an opportunity for treating neurological manifestations of GD/PD. Thiazolidinediones (TZDs, also called glitazones) are a class of compounds targeted for the treatment of type 2 diabetes, and have also shown promise for the treatment of neurodegenerative disease, including PD. Here, we tested the efficacy of glitazone administration during development in a fly GD model with deletions in the GBA homolog, dGBA1b (GBA1ΔTT/ΔTT). We observed an optimal dose of pioglitazone (PGZ) at a concentration of 1 μM that reduced sleep deficits, locomotor impairments, climbing defects, and restoration of normal protein levels of Ref(2)P, a marker of autophagic flux, in GBA1ΔTT/ΔTT mutant flies, compared to GBA1+/+ control flies. These data suggest that PGZ may represent a potential compound with which to treat GD/PD by improving function of lysosomal-autophagy pathways, a cellular process that removes misfolded or aggregated proteins.

The Canary Islands inhabitants, a recently admixed population with significant North African genetic influence, has the highest incidence of childhood-onset type 1 diabetes (T1D) in Spain and one of the highest in Europe. HLA accounts for half of the genetic risk of T1D., Aims: To characterize the classical HLA-DRB1 and HLA-DQB1 alleles in children from Gran Canaria with and without T1D., Methods: We analyzed classic HLA-DRB1 and HLA-DQB1 alleles in childhood-onset T1D patients (n = 309) and control children without T1D (n = 222) from the island of Gran Canaria. We also analyzed the presence or absence of aspartic acid at position 57 in the HLA-DQB1 gene and arginine at position 52 in the HLA-DQA1 gene. Genotyping of classical HLA-DQB1 and HLA-DRB1 alleles was performed at two-digit resolution using Luminex technology. The chi-square test (or Fisher's exact test) and odds ratio (OR) were computed to assess differences in allele and genotype frequencies between patients and controls. Logistic regression analysis was also used., Results: Mean age at diagnosis of T1D was 7.4 ± 3.6 years (46% female). Mean age of the controls was 7.6 ± 1.1 years (55% female). DRB1*03 (OR = 4.2; p = 2.13 -13 ), DRB1*04 (OR = 6.6; p ≤ 2.00 -16 ), DRB1* 07 (OR = 0.37; p = 9.73 -06 ), DRB1*11 (OR = 0.17; p = 6.72 -09 ), DRB1*12, DRB1*13 (OR = 0.38; p = 1.21 -05 ), DRB1*14 (OR = 0.0; p = 0.0024), DRB1*15 (OR = 0.13; p = 7.78 -07 ) and DRB1*16 (OR = 0.21; p = 0.003) exhibited significant differences in frequency between groups. Among the DQB1* alleles, DQB1*02 (OR: 2.3; p = 5.13 -06 ), DQB1*03 (OR = 1.7; p = 1.89 -03 ), DQB1*05 (OR = 0.64; p = 0.027) and DQB1*06 (OR = 0.19; p = 6.25 -14 ) exhibited significant differences. A total of 58% of the studied HLA-DQB1 genes in our control population lacked aspartic acid at position 57., Conclusions: In this population, the overall distributions of the HLA-DRB1 and HLA-DQB1 alleles are similar to those in other European populations. However, the frequency of the non-Asp-57 HLA-DQB1 molecules is greater than that in other populations with a lower incidence of T1D. Based on genetic, historical and epidemiological data, we propose that a common genetic background might help explain the elevated pediatric T1D incidence in the Canary Islands, North-Africa and middle eastern countries., (© 2024. The Author(s).)

Objective: To determine the impact and best management sequence between adenotonsillectomy (AT) and rapid palatal expansion (RPE) on the apnea-hypopnea index (AHI) and minimum oxygen saturation (MinSaO 2 ) in nonobese pediatric obstructive sleep apnea (OSA) patients presenting balanced maxillomandibular relationship., Study Design/methods: Thirty-two nonobese children with balanced maxillomandibular relationship and a mean age of 8.8 years, with a graded III/IV tonsillar hypertrophy and maxillary constriction, participated in a cross-over randomized controlled trial. As the first intervention, one group underwent AT while the other underwent RPE. After 6 months, interventions were switched in those groups, but only to participants with an AHI > 1 after the first intervention. OSA medical diagnosis with the support of Polysomnography (PSG) was conducted before (T 0 ), 6 months after the first (T 1 ) and the second (T 2 ) intervention. The influence of sex, adenotonsillar hypertrophy degree, initial AHI and MinSaO 2 severity, and intervention sequence were evaluated using linear regression analysis. Intra- and intergroup comparisons for AHI and MinSaO 2 were performed using ANOVA and Tukey's test., Results: The initial AHI severity and intervention sequence (AT first) explained 94.9% of AHI improvement. The initial MinSaO 2 severity accounted for 83.1% of MinSaO 2 improvement changes. Most AHI reductions and MinSaO 2 improvements were due to AT., Conclusions: Initial AHI severity and AT as the first intervention accounted for most of the AHI improvement. The initial MinSaO 2 severity alone accounted for the most changes in MinSaO 2 increase. In most cases, RPE had a marginal effect on AHI and MinSaO 2 when adjusted for confounders., (© 2024 Wiley Periodicals LLC.)

Background: Monoallelic loss-of-function IKZF1 (IKAROS) variants cause B-cell deficiency or combined immunodeficiency, whereas monoallelic gain-of-function (GOF) IKZF1 variants have recently been reported to cause hypergammaglobulinemia, abnormal plasma cell differentiation, autoimmune and allergic manifestations, and infections., Objective: We studied 7 relatives with autoimmune/inflammatory and lymphoproliferative manifestations to identify the immunologic disturbances and the genetic cause of their disease., Methods: We analyzed biopsy results and performed whole-exome sequencing and immunologic studies., Results: Disease onset occurred at a mean age of 25.2 years (range, 10-64, years). Six patients suffered from autoimmune/inflammatory diseases, 4 had confirmed IG4-related disease (IgG4-RD), and 5 developed B-cell malignancies: lymphoma in 4 and multiple myeloma in the remaining patient. Patients without immunosuppression were not particularly prone to infectious diseases. Three patients suffered from life-threatening coronavirus disease 2019 pneumonia, of whom 1 had autoantibodies neutralizing IFN-α. The recently described IKZF1 GOF p.R183H variant was found in the 5 affected relatives tested and in a 6-year-old asymptomatic girl. Immunologic analysis revealed hypergammaglobulinemia and high frequencies of certain lymphocyte subsets (exhausted B cells, effector memory CD4 T cells, effector memory CD4 T cells that have regained surface expression of CD45RA and CD28 - CD57 + CD4 + and CD8 + T cells, T H 2, and Tfh2 cells) attesting to immune dysregulation. Partial clinical responses to rituximab and corticosteroids were observed, and treatment with lenalidomide, which promotes IKAROS degradation, was initiated in 3 patients., Conclusions: Heterozygosity for GOF IKZF1 variants underlies autoimmunity/inflammatory diseases, IgG4-RD, and B-cell malignancies, the onset of which may occur in adulthood. Clinical and immunologic data are similar to those for patients with unexplained IgG4-RD. Patients may therefore benefit from treatments inhibiting pathways displaying IKAROS-mediated overactivity., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Patient-provider communication (PPC) is a critical component of patient-centered care. Original studies have examined specific factors related to PPC during consultations for elective dental procedures, but this evidence has yet to be comprehensively summarized. This scoping review aimed to understand better the extent and depth of the available literature regarding factors that influence PPC during consultations for elective dental procedures., Methods: The authors considered electronically available, English-language, original research published since 1990 assessing communication during consultations for elective dental procedures. Four electronic databases, Google Scholar, and reference lists of inclusions were searched until August 2023. No quality assessment was completed. Two independent researchers assessed article eligibility. Data were charted with a narrative review approach., Results: A total of 37 studies were included. The most popular discipline studied was orthodontics. Prospective cohorts and cross-sectional were the most common study designs. Information recall, patient satisfaction, and patient comprehension were the most common outcome measures. Most studies employed questionnaires, surveys, or interviews for data collection. Nineteen factors related to PPC during elective dental consultations were identified and categorized into information delivery (4), patient-related (9), and provider-related factors (6)., Conclusions: This scoping review is the first to present a list of evidence-supported factors related to PPC in elective dental consultations. Identifying these factors is an important first step to better understanding their influence on PPC and designing interventions targeting those that may be modifiable. PPC during elective dental consultations is a dynamic, ongoing process. Several recommendations emerged that may help improve PPC, including appropriate information delivery, patient engagement, providing adequate time, and educating ourselves on approaches to PPC., (Copyright © 2024 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Data Sources: The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Scopus, Web of Science, Google Scholar, Trip, CINAHL via EBSCO, EMBASE via OVID and ProQuest searched up to June 2023. Any clinical study with parallel arms and matched malocclusion severity should include permanent dentition participants with mild to mild-to-moderate anterior crowding. Participants should have undergone orthodontic treatment with either orthodontic labial fixed appliances or removable clear aligners. Total treatment time (primary outcome), chair time, number of appointments, and emergency visits (secondary outcomes) should also be reported., Study Selection: Two reviewers selected the studies to be considered in two stages. If needed, a third reviewer was included to solve discrepancies. Endnote and Rayyan software supported the process., Data Extraction and Synthesis: The same two reviewers independently extracted the required data from the included studies. If needed, a third reviewer was included to solve discrepancies. Endnote and Rayyan software supported the process., Results: Ten studies were finally included (six RCTs and four non-RCTs). Only one included samples in which teeth were extracted due to crowding. The total included sample was 718 participants (aged 20-29 years). Only one study did not report crowding equivalency between groups., Conclusions: Based on low to very low certainty levels, treatment duration is likely similar, chair time and emergency visits are less frequent, and the number of appointments is increased with clear aligners., (© 2024. The Author(s), under exclusive licence to British Dental Association.)

Background: North African human populations present a complex demographic scenario due to the presence of an autochthonous genetic component and population substructure, plus extensive gene flow from the Middle East, Europe, and sub-Saharan Africa., Results: We conducted a comprehensive analysis of 364 genomes to construct detailed demographic models for the North African region, encompassing its two primary ethnic groups, the Arab and Amazigh populations. This was achieved through an Approximate Bayesian Computation with Deep Learning (ABC-DL) framework and a novel algorithm called Genetic Programming for Population Genetics (GP4PG). This innovative approach enabled us to effectively model intricate demographic scenarios, utilizing a subset of 16 whole genomes at > 30X coverage. The demographic model suggested by GP4PG exhibited a closer alignment with the observed data compared to the ABC-DL model. Both point to a back-to-Africa origin of North African individuals and a close relationship with Eurasian populations. Results support different origins for Amazigh and Arab populations, with Amazigh populations originating back in Epipaleolithic times, while GP4PG supports Arabization as the main source of Middle Eastern ancestry. The GP4PG model includes population substructure in surrounding populations (sub-Saharan Africa and Middle East) with continuous decaying gene flow after population split. Contrary to ABC-DL, the best GP4PG model does not require pulses of admixture from surrounding populations into North Africa pointing to soft splits as drivers of divergence in North Africa., Conclusions: We have built a demographic model on North Africa that points to a back-to-Africa expansion and a differential origin between Arab and Amazigh populations., (© 2024. The Author(s).)

Background: The acceptability and preference for clear aligner therapy (CAT) has been increasing among orthodontists, but there is still a lack of consensus regarding CAT best practices. Consequently, this study aimed to investigate CAT practices among orthodontists practicing in Canada., Methods: The survey was conducted among orthodontists practicing in Canada using a modified previously published survey. Sixty orthodontists participated (6.1% response rate). It consisted of 11 sections with open and closed questions related to demographic information and particularities about using or not using CAT. The survey responses were exported from REDCap to a Microsoft Excel (Microsoft, Redmond, Wash) spreadsheet, then statistically analyzed using SPSS software (SPSS for Windows, version 21.0; IBM Inc., Armonk, NY, USA). The comments were categorized under themes and subthemes. Data were organized in descriptive statistics, expressing frequencies and percentages., Results: Almost 30% of the orthodontist's annual caseload was treated with CAT, most frequently prescribed to adult patients. Case complexity and patient cooperation were the factors that most influenced the decision to prescribe CAT. Almost half of orthodontists reported sometimes combining CAT with adjunctive fixed appliances., Conclusions: Most orthodontists prescribe CAT, and its use is based on the malocclusion's complexity. Orthodontists who do not prescribe CAT believe that fixed appliance therapy has superior treatment outcomes., (© 2024. The Author(s).)

With the growing popularity of clear aligners, more patients have chosen to use them instead of traditional orthodontic braces to correct their malocclusions. Clear aligners offer distinct advantages over conventional fixed braces, such as limited aesthetic impact, the convenience of easily removing them for meals, improved accessibility for brushing and flossing, and a treatment approach that avoids the use of metal, minimizing potential irritation to the cheeks and gums. Manufacturers point out a disadvantage that can be administered in this type of treatment. Still, to our knowledge, a comprehensive review of the published literature assessing the adverse/negative effects of clear aligners has not yet been conducted. A systematic review, with or without meta-analysis, will be performed. The inclusion criteria will be studies involving individuals using clear aligners and reporting potential adverse/negative effects during or after treatment. No restrictions about time or language will be applied. The studies screening will be conducted in two stages. Two independent reviewers will initially evaluate the title and abstract under the eligibility criteria. Subsequently, the same two reviewers will examine the articles' full text in-depth. The results will be synthesized in the form of a narrative description and incorporate a meta-analysis if justified. Furthermore, we will present details regarding the sample characteristics, intervention, study objectives, methodologies employed, and primary findings. This study aims to investigate the potential adverse effects and their frequency among orthodontic patients wearing clear aligners. Moreover, the outcomes of this review have the potential to illuminate specific inherent limitations of aligner therapy as a comprehensive orthodontic approach., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ronchi Lemos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: The medium-term effects of rapid maxillary expansion (RME) on nasal cavity (NC) and upper airway (UA) dimensions based on chronological age are still unclear. This retrospective study evaluated the medium-term changes occurring in the NC and pharyngeal airways (PA) after RME in two distinct age-based cohorts of patients., Methods: This retrospective study included 48 subjects who underwent RME grouped in two cohorts: a 6-9-year-old group (EEG group: early expansion group - 25 subjects) and an 11-14-year-old group (LEG group: late expansion group - 23 subjects). NC and PA volumes were analyzed from CBCT imaging segmentation before RME (T0) and twelve months after RME (T1). The amount of maxillary expansion (PW) and minimal cross-sectional area (CSmin) were also considered., Results: All PAs' volumetric sub-regions, CSmin and PW showed a significant volumetric increment (p < 0.05). Inter-group comparisons showed significant differences (p < 0.05) for nasopharynx and CSmin parameters (p < 0.05), while no significant changes were recorded for the other UA's sub-regions and PW (p > 0.05). According to a deviation analysis, part of the UA increase (more marked for the nasopharynx area) may have occurred due to reduced adenotonsillar tissues, which were larger in the EEG group., Conclusions: Twelve months after treatment, clinicians should not expect changes in the UAs dimensions to be solely related to treatment effects of RME; instead, normal craniofacial growth changes and spontaneous regression of the adenotonsillar tissue could represent the most significant factors influencing UAs changes., Clinical Significance: From the clinical perspective, the results of the present study encourage caution when considering the therapeutic effects of RME on airways dimensions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: To explore parents' experiences and perceptions regarding engagement in health services for managing residual paediatric obstructive sleep apnoea (OSA) across levels of care., Methods: Qualitative description guided study design. Data were collected through semi-structured interviews with parents of children diagnosed with residual OSA at a university-based sleep clinic. The relevant literature informed the interview guide and was piloted before data collection. Inductive, manifest content analysis was used to describe parents' perceptions and experiences using data-driven categories and sub-categories. Several strategies were employed to ensure rigour in this study., Results: Eight interviews were conducted. Parents' views were organized into five categories: awareness of the sleep issue, interaction with non-sleep specialists, interaction with sleep specialists, interaction with dental professionals, and further actions and support. Parents reported several engagement issues due to their interactions with different care providers. These issues included having to personally identify and raise the sleep problem, feeling that care providers did not take this problem seriously, waiting for an extended period to be referred for sleep services, and receiving conflicting or insufficient treatment recommendations. Overall, parents perceived that their actions and the services received across levels of care were not effective enough to address paediatric OSA., Conclusion: Based on this exploratory qualitative descriptive research, along with developing evidence-based clinical guidelines for paediatric OSA screening and management tailored to different levels of care, strategies intended to improve the engagement of patients and care providers in addressing paediatric OSA should be developed and empirically tested., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major human pathogens. It could carry numerous resistance genes and virulence factors in its genome, some of which are related to the severity of the infection. An observational, descriptive, cross-sectional study was designed to molecularly analyze MRSA isolates that cause invasive infections in Paraguayan children from 2009 to 2013. Ten representative MRSA isolates of the main clonal complex identified were analyzed with short-read paired-end sequencing and assessed for the virulome, resistome, and phylogenetic relationships. All the genetically linked MRSA isolates were recovered from diverse clinical sources, patients, and hospitals at broad gap periods. The pan-genomic analysis of these clones revealed three major and different clonal complexes (CC30, CC5, and CC8), each composed of clones closely related to each other. The CC30 genomes prove to be a successful clone, strongly installed and disseminated throughout our country, and closely related to other CC30 public genomes from the region and the world. The CC5 shows the highest genetic variability, and the CC8 carried the complete arginine catabolic mobile element (ACME), closely related to the USA300-NAE-ACME+, identified as the major cause of CA-MRSA infections in North America. Multiple virulence and resistance genes were identified for the first time in this study, highlighting the complex virulence profiles of MRSA circulating in the country. This study opens a wide range of new possibilities for future projects and trials to improve the existing knowledge on the epidemiology of MRSA circulating in Paraguay., Importance: The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is a public health problem worldwide. The most frequent MRSA clones identified in Paraguay in previous studies (including community and hospital acquired) were the Pediatric (CC5-ST5-IV), the Cordobes-Chilean (CC5-ST5-I), the SouthWest Pacific (CC30-ST30-IV), and the Brazilian (CC8-ST239-III) clones. In this study, the pan-genomic analysis of the most representative MRSA clones circulating in invasive infection in Paraguayan children over the years 2009-2013, such as the CC30-ST30-IV, CC5-ST5-IV, and CC8-ST8-IV, was carried out to evaluate their genetic diversity, their repertoire of virulence factors, and antimicrobial resistance determinants. This revealed multiple virulence and resistance genes, highlighting the complex virulence profiles of MRSA circulating in Paraguay. Our work is the first genomic study of MRSA in Paraguay and will contribute to the development of genomic surveillance in the region and our understanding of the global epidemiology of this pathogen., Competing Interests: The authors declare no conflict of interest.

We explored patient front-line treatment preferences in newly diagnosed stage III/IV classic Hodgkin lymphoma (cHL). The CONNECT patient survey, administered online from 30 December 2020 to 1 March 2021, examined preferences overall and by age at diagnosis in 182 adult patients diagnosed with stage III/IV cHL within the past 10 years in the United States. At diagnosis, patients' median age was 36 years; 66% of patients were younger (aged 16-41 years) and 34% older (aged 42-85 years). When asked about initial treatment goals, 74% of patients ranked cure as their first or second goal (86% younger vs. 52% older patients; p < 0.001). At diagnosis, 72% of patients preferred aggressive treatment, and 85% were willing to accept more short-term risks in exchange for a better-working therapy long term. For long-term risks, younger versus older patients were significantly more concerned about second cancers (p < 0.001) and fertility issues (p = 0.007), whereas older patients were more concerned about lung damage (p = 0.028) and infections (p < 0.001). Most patients (94%) reported having a caregiver at some point, but 99% of these patients retained some control of treatment decisions. Collectively, these survey results highlight patient treatment preferences and differences in treatment goals and long-term side effect concerns based on patient age., (© 2024 Pfizer Inc and The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Aim: To understand US physicians' frontline (1L) treatment preferences/decision-making for stage III/IV classic Hodgkin lymphoma (cHL). Materials & methods: Medical oncologists and/or hematologists (≥2 years' practice experience) who treat adults with stage III/IV cHL were surveyed online (October-November 2020). Results: Participants (n = 301) most commonly considered trial efficacy/safety data and national guidelines when selecting 1L cHL treatments. Most physicians (91%) rated overall survival (OS) as the most essential attribute when selecting 1L treatment. Variability was seen among regimen selection for hypothetical newly diagnosed patients, with OS cited as the most common reason for regimen selection. Conclusion: While treatment selection varied based on patient characteristics, US physicians consistently cited OS as the top factor considered when selecting a 1L treatment for cHL.

Background: Orthodontic systematic reviews (SRs) use different methods to pool the individual studies in a meta-analysis when indicated. However, the number of studies included in orthodontic meta-analyses is relatively small. This study aimed to evaluate the direction of estimate changes of orthodontic meta-analyses (MAs) using different between-study variance methods considering the level of heterogeneity when few trials were pooled., Methods: Search and study selection: Systematic reviews (SRs) published over the last three years, from the 1st of January 2020 to the 31st of December 2022, in six main orthodontic journals with at least one MA pooling five or lesser primary studies were identified. Data collection and analysis: Data were extracted from each eligible MA, which was replicated in a random effect model using DerSimonian and Laird (DL), Paule-Mandel (PM), Restricted maximum-likelihood (REML), Hartung Knapp and Sidik Jonkman (HKSJ) methods. The results were reported using median and interquartile range (IQR) for continuous data and frequencies for categorical data and analyzed using non-parametric tests. The Boruta algorithm was used to assess the significant predictors for the significant change in the confidence interval between the different methods compared to the DL method, which was only feasible using the HKSJ method., Results: 146 MAs were included, most applying the random effect model (n = 111; 76%) and pooling continuous data using mean difference (n = 121; 83%). The median number of studies was three (range 2, 4), and the overall statistical heterogeneity (I2 ranged from 0 to 99% with a median of 68%). Close to 60% of the significant findings became non-significant when HKSJ was applied compared to the DL method and when the heterogeneity was present I2>0%. On the other hand, 30.43% of the non-significant meta-analyses using the DL method became significant when HKSJ was used when the heterogeneity was absent I2 = 0%., Conclusion: Orthodontic MAs with few studies can produce different results based on the between-study variance method and the statistical heterogeneity level. Compared to DL, HKSJ method is overconservative when I2 is greater than 0% and may result in false positive findings when the heterogeneity is absent., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mheissen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to evaluate the association between single nucleotide polymorphisms (SNPs) in endochondral development-related genes and mandibular condyle shape, size, volume, and symmetry traits. Cone-beam Computed Tomographies and genomic DNA from 118 individuals were evaluated (age range: 15-66 years). Data from twelve 3D landmarks on mandibular condyles were submitted to morphometric analyses including Procrustes fit, principal component analysis, and estimation of centroid sizes and fluctuating asymmetry scores. Condylar volumes were additionally measured. Seven SNPs across BMP2, BMP4, RUNX2 and SMAD6 were genotyped. Linear models were fit to evaluate the effect of the SNPs on the mandibular condyles' quantitative traits. Only the association between BMP2 rs1005464 and centroid size remained significant after adjusting to account for the false discovery rate due to multiple testing. Individuals carrying at least one A allele for this SNP showed larger condylar size than common homozygotes GG (β = 0.043; 95% CI: 0.014-0.071; P value = 0.028). The model including BMP2 rs1005464, age and sex of the participants explained 17% of the variation in condylar size. Shape, volume, and symmetry were not associated with the evaluated SNPs. These results suggest that BMP2 rs1005464 might be associated with variation in the mandibular condyles size., (© 2024. The Author(s).)

Aim: To evaluate the maxillary incisors and canine's immediate movement tendency using three different power arms (PA) height levels during total arch maxillary distalization supported on infrazygomatic crest (IZC) miniscrews according to finite element analysis (FEA)., Methods: Three finite element models of the maxilla were developed based on CBCT imaging of a teenage male patient presenting a Class II Division 1 malocclusion in the early permanent dentition. Maxillary complex, periodontium, orthodontic accessories, IZC miniscrews and an orthodontic wire were digitally created. The PAs were placed between canines and lateral incisors and projected at 4, 7, and 10 mm height distances. After that, distalization forces were simulated between PA and IZC miniscrews., Results: The anterior teeth deformation produced in the FEA models was assessed according to a Von Mises equivalent. The stress was measured, revealing tendencies of initial maxillary teeth movement. No differences were found between the right and left sides. However, there was a significant difference among models in the under-stress areas, especially the apical and cervical root areas of the maxillary anterior teeth. More significant extrusion and lingual tipping of incisors were observed with the 4 mm power arm compared to the 7 mm and 10 mm ones. The 10 mm power arm did not show any tendency for extrusion of maxillary central incisors but a tendency for buccal tipping and intrusion of lateral incisors., Conclusion: The maxillary incisors and canines have different immediate movement tendencies according to the height of the anterior point of the en-masse distalization force application. Based on the PA height increase, a change from lingual to buccal tipping and less extrusion tendency was observed for the incisors, while the lingual tipping and extrusion trend for canines increased., (© 2024. The Author(s).)

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF, and a prior association of the HLA-DQB1 gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Owing to the important role that the human leukocyte antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk., Methods: We performed a meta-analysis of associations of the HLA region with IPF risk in individuals of European ancestry from seven independent case-control studies of IPF (comprising 5159 cases and 27 459 controls, including a prior study of fibrotic interstitial pneumonia). Single nucleotide polymorphisms, classical HLA alleles and amino acids were analysed and signals meeting a region-wide association threshold of p<4.5×10 -4 and a posterior probability of replication >90% were considered significant. We sought to replicate the previously reported HLA-DQB1 association in the subset of studies independent of the original report., Results: The meta-analysis of all seven studies identified four significant independent single nucleotide polymorphisms associated with IPF risk. However, none met the posterior probability for replication criterion. The HLA-DQB1 association was not replicated in the independent IPF studies., Conclusion: Variation in the HLA region was not consistently associated with risk in studies of IPF. However, this does not preclude the possibility that other genomic regions linked to the immune response may be involved in the aetiology of IPF., Competing Interests: Conflict of interest: L.J. Donoghue, A. Stockwell, M. Neighbours, X.R. Sheng and B.L. Yaspan are full-time employees of Genentech; A. Stockwell, M. Neighbours, X.R. Sheng and B.L. Yaspan hold stock options in Roche. J.M. Oldham reports personal fees from Boehringer Ingelheim, Genentech, United Therapeutics, AmMax Bio and Lupin Pharmaceuticals outside the submitted work. D.A. Schwartz is the founder and chief scientific officer of Eleven P15, a company focused on the early detection and treatment of pulmonary fibrosis. R.G. Jenkins reports honoraria from Chiesi, Roche, PatientMPower, AstraZeneca, GlaxoSmithKline and Boehringer Ingelheim, and consulting fees from Bristol Myers Squibb, Daewoong, Veracyte, Resolution Therapeutics, RedX, Pliant and Chiesi. L.V. Wain reports research funding from GlaxoSmithKline, Roche and Orion Pharma, and consultancy for GlaxoSmithKline and Galapagos, outside of the submitted work. S.P. Hart and P.L. Molyneaux are associate editors of this journal. The other authors declare no competing interests., (Copyright ©The authors 2024.)

Background: Genome-wide association studies of COVID-19 severity have been carried out mostly on European or East Asian populations with small representation of other world regions. Here we explore the worldwide distribution and linkage disequilibrium (LD) patterns of genetic variants previously associated with COVID-19 severity., Methods: We followed up the results of a large Spanish genome-wide meta-analysis on 26 populations from the 1000 Genomes Project by calculating allele frequencies and LD scores of the nine most significant SNPs. We also used the entire set of summary statistics to compute polygenic risk scores (PRSs) and carried out comparisons at the population and continental level., Results: We observed the strongest differences among continental regions for the five top SNPs in chromosome 3. European, American, and South Asian populations showed similar LD patterns. Average PRSs in South Asian and American populations were consistently higher than those observed in Europeans. While PRS distributions were similar among South Asians, the American populations showed striking differences among them., Conclusions: Considering the caveats of PRS transferability across ethnicities, our analysis showed that American populations present the highest genetic risk score, hence potentially higher propensity, for COVID-19 severity. Independent validation is warranted with additional summary statistics and phenotype data.

Objective: To assess if the dental follicle volume of palatally impacted canines (PICs) affects the relative root position of the adjacent lateral incisors (LIs) and first premolars (FPs)., Materials and Methods: A retrospective cross-sectional study of 49 patients with unilaterally PICs with dental follicles who had CBCT imaging previously taken. Four orthodontic centers in different countries provided the sample. A mean difference of 5° between the angular measurements (mesiodistal tip, buccolingual inclination, or mesiodistal rotation) of the LI and FP adjacent to the PIC and the controls was considered clinically relevant. A value of 0.05 was set for significance level and a power of 80%. The minimum sample size was determined to be 26 patients. These patients were further assigned to an LI sample (n = 49) and an FP sample (n = 23), dependent on the direct contact of the dental follicle to that adjacent tooth. A manual segmentation technique was used to obtain the volumetric measurements of the dental follicle. Angular measurements of adjacent teeth were then compared to the contralateral nonimpacted side, which acted as the control. A multivariant regression analysis was performed using IBM SPSS software, and statistical significance was set at α = 0.05., Results: Adequate intra-rater reliability was accomplished. The multivariant regression analysis implied that there is no difference in the mean change in the tip, torque, and rotation of the LI and FP between the impacted and control sides when dental follicle volumes are considered (P = .509 for the LI sample and P = .804 for the FP sample)., Limitations: CBCT imaging of dental follicle border delimitations, partial volume effect, and scattering are limitations. This is a convenience sample where the FP subsample is small., Conclusion: The dental follicle volume of the PICs does not seem to influence the relative position of the adjacent LI and FP mesiodistal tip, buccolingual inclination, and mesiodistal rotation. Early intervention could have been suggested to avoid certain malocclusion traits if significant displacements were demonstrated., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Orthodontic retainers are widely used to prevent relapses after orthodontic treatment; however, evidence about patients' perceptions of retainers is lacking., Objective: To assess patients' perception of orthodontic retainers., Search Methods: PubMed, Web of Science, Scopus, LILACS, LIVIVO, Cochrane Library, and gray literature (Google Scholar) were searched without date or language restrictions. A manual search of the reference lists of the included articles was also performed., Selection Criteria: Studies comparing patients' perceptions of wearing orthodontic retainers were included., Data Collection and Analysis: According to the study design, the risk of bias (RoB) assessment was performed using RoB 2.0 or ROBINS-I. The level of evidence was assessed through the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) tool., Results: Seventeen studies met the eligibility criteria. After the RoB assessment, 12 randomized controlled trials presented a high RoB, and 4 non-randomized controlled trials presented a moderate RoB. The certainty of evidence was classified as very low for the four assessed outcomes. The studies generally reported an initial temporary negative impact of orthodontic retainers. Different esthetic, functional, and ease-of-use advantages are reported using removable and fixed retainers. A quantitative analysis was not performed due to the considerable clinical and methodological heterogeneity among the studies., Conclusion: The current evidence, although very limited, suggests that orthodontic retainers have an initial negative impact related to discomfort and functional limitations, but they seem to regress over time. There is a preference for thermoplastic over Hawley-type retainers. However, thermoplastic retainers cause different functional difficulties, and bonded retainers present the advantage of affecting speech function less than orthodontic removable retainers, although they can facilitate oral hygiene problems., Registration: PROSPERO (CRD42022306665)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

ABSTRACT The emergence of the Omicron SARS-CoV-2 variant of concern has changed the COVID-19 scenario as this variant is characterized by high transmissibility and immune evasion ability. To evaluate the impact of this variant on the Canary Islands (Spain) population, we determined the reinfection rates and disease severity associated with the Omicron sublineages and the previously circulating variants of concern. We performed a retrospective observational study on 21,745 SARS-CoV-2 viral genomes collected from December 2020 to July 2022 in the Canary Islands (Spain). We compared the reinfection rates between lineages using pairwise proportion and Fisher's exact tests. To assess disease severity, we studied the association of Alpha, Delta, BA.1, BA.2, BA.5, and other risk factors on 28-day hospital mortality using logistic regression and Cox proportional hazard models. We observed 127 bona fide reinfection cases throughout the study period. We found that BA.5 had the highest reinfection rate compared to other lineages (vs. Delta p =  2.89 × 10 -25 ; vs. BA.1 p =  5.17 × 10 -11 ; vs. BA.2 p =  0.002). Among the 1,094 hospitalized patients, multivariate logistic regression showed that Alpha (Odds Ratio [OR] =  0.45, 95% Confidence Interval [CI] =  0.23-0.87, p =  0.02), BA.2 (OR =   0.38, 95% CI = 0.22-0.63, p =  1.91 × 10 -4 ), and BA.5 (OR = 0.30, 95% CI = 0.16-0.55, p =  1.05 × 10 -4 ) had lower 28-day hospital mortality compared to Delta. These results were confirmed by using Cox proportional hazard models. Omicron lineages, and in particular BA.5, were associated with higher reinfection rates and lower disease severity (28-day hospital mortality) than previously circulating variants of concern.

We analyzed the association between HLA polymorphisms and susceptibility to SARS-CoV-2 infection and disease severity. Genotyping data from a total of 9373 COVID-19-positive cases from the Spanish Coalition to Unlock Research on Host Genetics on COVID-19 (SCOURGE) consortium and 5943 population controls were included in the study. We found an association of the alleles HLA-B*14:02 and HLA-C*08:02 with a lower risk to COVID-19 infection (p = 0.006, OR = 0.84, 95% CI = [0.75-0.95], p = 0.024, OR = 0.86, 95% CI = [0.78-0.95], respectively). We also found the alleles HLA-A*11:01 and HLA-C*04:01 associated with disease severity (p = 0.033, OR = 1.16, 95% CI = [1.04-1.31], p = 0.045, OR = 1.14, 95% CI = [1.05-1.25], respectively). These results suggest that an effective presentation of viral peptides by HLA class I alleles involve a faster infection clearance, decreasing the susceptibility and severity of COVID-19., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Urinary tract infection is among the most common infections worldwide, typically studied in animals and cell lines with limited uropathogenic strains. Here, we assessed diverse bacterial species in a human urothelial microtissue model exhibiting full stratification, differentiation, innate epithelial responses, and urine tolerance. Several uropathogens invaded intracellularly, but also commensal Escherichia coli , suggesting that invasion is a shared survival strategy, not solely a virulence hallmark. The E. coli adhesin FimH was required for intracellular bacterial community formation, but not for invasion. Other shared lifestyles included filamentation (Gram-negatives), chaining (Gram-positives), and hijacking of exfoliating cells, while biofilm-like aggregates were formed mainly with Pseudomonas and Proteus . Urothelial cells expelled invasive bacteria in Rab-/LC3-decorated structures, while highly cytotoxic/invasive uropathogens, but not commensals, disrupted host barrier function and strongly induced exfoliation and cytokine production. Overall, this work highlights diverse species-/strain-specific infection strategies and corresponding host responses in a human urothelial microenvironment, providing insights at the microtissue, cell, and molecular level.

Objectives: Treatments that prevent sepsis complications are needed. Circulating lipid and protein assemblies-lipoproteins play critical roles in clearing pathogens from the bloodstream. We investigated whether early inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) may accelerate bloodstream clearance of immunogenic bacterial lipids and improve sepsis outcomes., Design: Genetic and clinical epidemiology, and experimental models., Setting: Human genetics cohorts, secondary analysis of a phase 3 randomized clinical trial enrolling patients with cardiovascular disease (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402), and experimental murine models of sepsis., Patients or Subjects: Nine human cohorts with sepsis (total n = 12,514) were assessed for an association between sepsis mortality and PCSK9 loss-of-function (LOF) variants. Incident or fatal sepsis rates were evaluated among 18,884 participants in a post hoc analysis of ODYSSEY OUTCOMES. C57BI/6J mice were used in Pseudomonas aeruginosa and Staphylococcus aureus bacteremia sepsis models, and in lipopolysaccharide-induced animal models., Interventions: Observational human cohort studies used genetic PCSK9 LOF variants as instrumental variables. ODYSSEY OUTCOMES participants were randomized to alirocumab or placebo. Mice were administered alirocumab, a PCSK9 inhibitor, at 5 mg/kg or 25 mg/kg subcutaneously, or isotype-matched control, 48 hours prior to the induction of bacterial sepsis. Mice did not receive other treatments for sepsis., Measurements and Main Results: Across human cohort studies, the effect estimate for 28-day mortality after sepsis diagnosis associated with genetic PCSK9 LOF was odds ratio = 0.86 (95% CI, 0.67-1.10; p = 0.24). A significant association was present in antibiotic-treated patients. In ODYSSEY OUTCOMES, sepsis frequency and mortality were infrequent and did not significantly differ by group, although both were numerically lower with alirocumab vs. placebo (relative risk of death from sepsis for alirocumab vs. placebo, 0.62; 95% CI, 0.32-1.20; p = 0.15). Mice treated with alirocumab had lower endotoxin levels and improved survival., Conclusions: PCSK9 inhibition may improve clinical outcomes in sepsis in preventive, pretreatment settings., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Purpose: As part of the CONNECT study, we evaluated the caregiver role in treatment decision-making when caring for patients with classic Hodgkin lymphoma (cHL) in the USA., Methods: The CONNECT caregiver survey was administered online December 2020-March 2021 to self-identified adult caregivers of cHL patients recruited from patient referrals and online panels. The caregiver's role in treatment decision-making, health-related quality of life (HRQoL, PROMIS-Global), and work impacts (WPAI:CG) were assessed., Results: We surveyed 209 caregivers (58% women; median age 47 years; 54% employed; 53% spouse/partner); 69% of patients cared for were diagnosed with cHL in the past 1-2 years, with 48% having stage III/IV cHL and 29% in remission. More spouse/partner than other caregivers were involved in caregiving at symptom onset (61% vs 27%), whereas more other than spouse/partner caregivers began after first treatment (34% vs 5%). Cure, caregivers' top treatment goal (49%), was rated higher by spouse/partner than other caregivers (56% vs 42%). More spouse/partner than other caregivers were involved in treatment option discussions with physicians (52% vs 28%), were involved in patients' treatment decisions (54% vs 23%), and were aligned with patients' treatment goals (93% vs 79%). While caregivers reported HRQoL similar to that of the general population, nearly 30% of employed caregivers reported work impairment., Conclusion: Cure was caregivers' top treatment goal. Spouse/partner vs other caregivers were more involved, were involved earlier, and reported greater alignment with patient treatment goals and decision-making. Caregivers reported good HRQoL; however, caregiving impacted work productivity regardless of patient relationship., (© 2023. The Author(s).)

Objectives: To identify the prevalence of Awake Bruxism (AB)., Sources: The electronic search was done in Embase, PubMed/MEDLINE, LILACS, Livivo, Scopus, and Web of Science databases up to January 2nd, 2023. The search strategies combined terms such as "bruxism," "awake," and related terms when conducting searches in databases. Grey literature was consulted through Google Scholar, ProQuest, and OpenGrey., Study Selection: Two independent reviewers participated in the study selection stages and included observational studies assessing the prevalence of AB, detected using reporting feedback (self or family report), clinical examination, and/or instrumental methods, regardless of the sex and age of the population., Data: Methodological quality was assessed using the Joanna Briggs Institute's checklist for prevalence studies. Ratio meta-analyses were performed using R Statistics software., Results: From a total of 3,083 studies identified by the searches on databases, 322 articles were reviewed the full-text and a total of 81 (quantitative synthesis) and 83 (narrative synthesis) studies were included. Only fifteen studies reached complete methodological quality. Two overall meta-analyses were performed, grouped based on convenience and population-based samples. The overall prevalence for possible AB was 32.08 % and 16.16 %, respectively. For the subgroup analyses, the prevalence rate showed a wide variation in different studied populations, approximately 14 %-32 % for women and 19 %-30 % for men, for population-based and convenience studies, respectively., Conclusion: Possible AB prevalence was set from 16 % to 32 %. Studies with probable AB and definitive AB are still necessary., Clinical Significance: Studying the prevalence of waking bruxism is of interest to both dentists and patients. Knowing the probability of patients having awake bruxism allows the dentist to offer comprehensive preventive approaches to patients, avoiding deleterious consequences resulting from this condition. The present study reveals that the condition of bruxism during wakefulness is present in one out of every six adult patients studied. In pediatric patients, although this condition seems to be equally present, not enough studies were found to support this information for probable and definitive bruxism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Study Objectives: We conducted this study to identify phenotypes of obstructive sleep apnea (OSA) in children based on lifestyle, sleep habits, age, obesity, sex, soft tissue facial features, and specific craniofacial abnormalities., Methods: Seventy-three children with symptoms of pediatric OSA who underwent overnight observed polysomnography participated in this study. Soft tissue facial features were assessed using a 3-dimensional stereophotogrammetric system. Craniofacial abnormalities were evaluated based on the most common facial features associated with orthodontic treatment needs. Data regarding lifestyle, sleep habits, age, obesity, and sex were also collected. To identify phenotypes of OSA, a sequential analysis was then performed on categories of variables using fuzzy clustering with medoids., Results: Craniofacial abnormalities and soft tissue facial features defined clusters. Three clusters were identified. Cluster 1 comprised a group of younger children (5.9 ± 3.8 years) without obesity, without craniofacial abnormalities, and with smaller soft tissue facial features dimensions. Cluster 2 comprised a group of older children (9.6 ± 3.9 years) without obesity and with larger mandibular dimensions and mildly arched palates (71.4%). Cluster 3 comprised a group of older children (9.2 ± 3.9 years) with obesity and a history of health issues (68.4%), excessive lower facial height (63.2%), and midface deficiency (73.7%). No differences were observed across clusters regarding sleep features. A moderate severity of obstructive and mixed respiratory events was observed in all 3 clusters., Conclusions: The study results did not identify distinct phenotypes of pediatric OSA based on soft tissue facial features or craniofacial abnormalities alone. Age and body mass index likely modify the effect of soft tissue facial features and craniofacial abnormalities as risk factors for OSA in children., Citation: Fernandes Fagundes NC, Loliencar P, MacLean JE, Flores-Mir C, Heo G. Characterization of craniofacial-based clinical phenotypes in children with suspected obstructive sleep apnea. J Clin Sleep Med . 2023;19(11):1857-1865., (© 2023 American Academy of Sleep Medicine.)

Maxillary central incisors are critical to occlusal function, smile esthetics, and even one's self-image. Furthermore, their impaction at an early age could have harmful psychological consequences on the individual. Maxillary central incisors can be impacted due to early dentoalveolar trauma to the upper anterior region that displaces the incisor in formation and, in rare instances, tooth germs are deformed. The aftermath of trauma during primary dentition is seen later during mixed dentition. Other causes are either an impediment in the eruption pathway of the maxillary central incisor due to the presence of odontomas or supernumerary teeth, an insufficient eruption space, or, very rarely, syndromic and/or other general medical conditions. Diagnosis is completed through a detailed medical/dental history, clinical evaluation, and appropriate imaging. Arch width increase, space opening, removal of obstructions if present, suitable soft-tissue management, well-designed orthodontic traction mechanics, and long-term periodontal follow-up are all essential elements in resolving cases of impacted maxillary central incisors.

In anthropological, medical, and forensic studies, the nonrecombinant region of the human Y chromosome (NRY) enables accurate reconstruction of pedigree relationships and retrieval of ancestral information. Using high-throughput sequencing (HTS) data, we present a benchmarking analysis of command-line tools for NRY haplogroup classification. The evaluation was performed using paired Illumina data from whole-genome sequencing (WGS) and whole-exome sequencing (WES) experiments from 50 unrelated donors. Additionally, as a validation, we also used paired WGS/WES datasets of 54 individuals from the 1000 Genomes Project. Finally, we evaluated the tools on data from third-generation HTS obtained from a subset of donors and one reference sample. Our results show that WES, despite typically offering less genealogical resolution than WGS, is an effective method for determining the NRY haplogroup. Y-LineageTracker and Yleaf showed the highest accuracy for WGS data, classifying precisely 98% and 96% of the samples, respectively. Yleaf outperforms all benchmarked tools in the WES data, classifying approximately 90% of the samples. Yleaf, Y-LineageTracker, and pathPhynder can correctly classify most samples (88%) sequenced with third-generation HTS. As a result, Yleaf provides the best performance for applications that use WGS and WES. Overall, our study offers researchers with a guide that allows them to select the most appropriate tool to analyze the NRY region using both second- and third-generation HTS data., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Purpose: To critically evaluate the evidence on knowledge changes observed after the application of evidence-based dentistry (EBD) educational interventions to dental students., Methods: We included studies that assessed EBD knowledge after applying educational interventions to undergraduates. Studies that evaluated post-graduate students or professionals, that exclusively described educational interventions, programs, or the application of curriculum revisions were excluded. Electronic databases (PubMed, Embase, Scopus, and Web of Science), unpublished gray literature, and manual searches were performed. Data concerning "perceived" and "actual knowledge" was extracted. The quality of the studies was appraised according to the Mixed Methods Appraisal Tool., Results: The 21 selected studies enrolled students at different stages, and the intervention formats were diverse. The educational interventions could be categorized into three modalities, that is, regular, EBD-focused disciplines or courses, and other educational interventions including one or more of the EBD principles, methods, and/or practices. Despite the format, knowledge was generally improved after the implementation of educational interventions. Overall, perceived and actual levels of knowledge increased considering EBD general concepts, principles, and/or practices, and concerning the "acquire" and "appraise" skills. Among the selected studies, two were randomized controlled trials, while most were non-randomized or descriptive studies., Conclusions: EBD-related educational interventions seem to improve dental students' perceived and actual knowledge, according to literature with a high risk of bias. Therefore, more complete, methodologically rigorous, and longer-term studies are still recommended to confirm and expand the current knowledge., (© 2023 American Dental Education Association.)

Background: The aim of the study was to analyze and compare external root resorption (ERR) in patients treated with tooth-borne (TB) and bone-borne (BB) rapid maxillary expansion (RME)., Methods: The sample included 40 subjects who received tooth-borne RME (TB group, average age: 13.1 ± 1.08 years) or bone-borne RME (BB group, average age: 14.5 ± 1.11 years) and Cone-beam computed tomography (CBCT) scans before treatment (T0) and after 3-month of retention (T1). A specific 3D Imaging technology was used to generate 3D models of posterior dentition (M1 = maxillary first molars, P2 = second premolars, P1 = first premolar) and calculate volumetric data (mean and percentage values) and shape changes, the latter obtained from deviation analysis between the radicular models at different time points. Evaluation of radicular length changes was performed for each tooth. Data were statistically analysed to perform intra-timing and inter-groups comparisons., Results: A significant reduction of radicular volume and length was found in posterior dentition in both groups (p < 0.05), and the M1 (volume) and its palatal root (length) were mostly involved in this response. No differences were found between M1, P1 and P2 (p > 0.05) when volumetric changes were calculated as percentage of the total volume. Deviation analysis revealed that the radicular areas mostly affected by shape change were the apex and bucco-medial side. The amount of ERR was significantly greater in TB group compared to BB group., Conclusions: BB-RME treatment could reduce the amount of ERR at the post-expansion stage., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To develop a well-detailed and reproducible tooth segmentation method, when quantifying tooth volumetric measurements is needed., Material and Methods: This was an in vitro study in which lower incisors and canines of five patients were 3D reconstructed by means of an automatic segmentation with manual refinements process. All the images were obtained using a 0.3-mm voxel size CBCT imaging. The software utilized was the ITK-SNAP®. The primary outcomes were the intra-rater and inter-rater reliabilities and the respective measurement errors., Results: The intra-rater reliability was excellent, with a mean measurement error of 4.16%. The inter-rater reliability was good, with a mean measurement error of 7.11%. Accuracy assessment was not possible, as the assessed teeth were not extracted., Conclusions: Although the described method is reliable, tooth volumetric error measurements may become significant, depending on the assessed situation.