Sensory Communication

Contains table of contents for Section 2, an introduction and reports on twelve research projects.National Institutes of Health Grant 5 R01 DC00117National Institutes of Health Contract 2 P01 DC00361National Institutes of Health Grant 5 R01 DC00126National Institutes of Health Grant R01-DC00270U.S. Air Force - Office of Scientific Research Contract AFOSR-90-0200National Institutes of Health Grant R29-DC00625U.S. Navy - Office of Naval Research Grant N00014-88-K-0604U.S. Navy - Office of Naval Research Grant N00014-91-J-1454U.S. Navy - Office of Naval Research Grant N00014-92-J-1814U.S. Navy - Naval Training Systems Center Contract N61339-93-M-1213U.S. Navy - Naval Training Systems Center Contract N61339-93-C-0055U.S. Navy - Naval Training Systems Center Contract N61339-93-C-0083U.S. Navy - Office of Naval Research Grant N00014-92-J-4005U.S. Navy - Office of Naval Research Grant N00014-93-1-119

Sensory Communication

Contains table of contents for Section 2 and reports on five research projects.National Institutes of Health Contract 2 R01 DC00117National Institutes of Health Contract 1 R01 DC02032National Institutes of Health Contract 2 P01 DC00361National Institutes of Health Contract N01 DC22402National Institutes of Health Grant R01-DC001001National Institutes of Health Grant R01-DC00270National Institutes of Health Grant 5 R01 DC00126National Institutes of Health Grant R29-DC00625U.S. Navy - Office of Naval Research Grant N00014-88-K-0604U.S. Navy - Office of Naval Research Grant N00014-91-J-1454U.S. Navy - Office of Naval Research Grant N00014-92-J-1814U.S. Navy - Naval Air Warfare Center Training Systems Division Contract N61339-94-C-0087U.S. Navy - Naval Air Warfare Center Training System Division Contract N61339-93-C-0055U.S. Navy - Office of Naval Research Grant N00014-93-1-1198National Aeronautics and Space Administration/Ames Research Center Grant NCC 2-77

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on fifteen research projects.National Institutes of Health Grant RO1 DC00117National Institutes of Health Grant RO1 DC02032National Institutes of Health Contract P01-DC00361National Institutes of Health Contract N01-DC22402National Institutes of Health/National Institute on Deafness and Other Communication Disorders Grant 2 R01 DC00126National Institutes of Health Grant 2 R01 DC00270National Institutes of Health Contract N01 DC-5-2107National Institutes of Health Grant 2 R01 DC00100U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-94-C-0087U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-95-K-0014U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-93-1-1399U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-94-1-1079U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research Grant N00014-92-J-1814National Institutes of Health Grant R01-NS33778U.S. Navy - Office of Naval Research Grant N00014-88-K-0604National Aeronautics and Space Administration Grant NCC 2-771U.S. Air Force - Office of Scientific Research Grant F49620-94-1-0236U.S. Air Force - Office of Scientific Research Agreement with Brandeis Universit

Prompt Referral in the Nonoperative Treatment of Obstetrical Brachial Plexus Injuries

Background:. Prompt physical and occupational therapy is crucial in managing nonsurgical candidates with obstetrical brachial plexus injuries (OBPI). The objective of our study was to identify newborns suffering from nonoperative OBPI in need of a “fast-track” evaluation by a multidisciplinary team. Methods:. This is a retrospective review of patients with OBPI from June 1995 to June 2015. All nonsurgical candidates (Narakas class 1) were included in the study. The Gilbert score and the Medical Research Council grading system were used to measure shoulder and elbow function, respectively. The relationship between shoulder and elbow functional outcomes and time delay to consultation was studied using analysis of variance and Welch’s tests. Various subgroups were studied based on OBPI risk factors: maternal diabetes, birth weight >4 kg, use of forceps, asphyxia, multiple comorbidities, and Apgar score at 1 and 5 minutes. Results:. A total of 168 patients were included in this study. Mean follow-up time was 313.8 weeks (minimum: 52; maximum: 1072; SD: 228.1). A total of 19 patients had an Apgar scores <7 at 5 minutes. Time delay between birth and the first consult to our clinic had an impact on shoulder outcome in the subgroup of newborns with Apgar scores <7 at 5 minutes. Conclusions:. The subgroup of newborns with an Apgar score <7 at 5 minutes shows improved long-term shoulder function when promptly examined by an OBPI clinic. We recommend a “fast-track” referral for this time-sensitive population

Etiology, histology, and long-term outcome of bilateral testicular regression: a large Belgian series

STUDY QUESTION: What is the long-term outcome of individuals born with bilateral testicular regression (BTR) in relation to its underlying etiology? SUMMARY ANSWER: Statural growth and pubertal development are adequate with incremental doses of testosterone replacement therapy (TRT); however, penile growth is often suboptimal, especially in those with a suspected genetic etiology (i.e. heterozygous DHX37 variants) or a micropenis at birth. WHAT IS KNOWN ALREADY: BTR is a rare and poorly understood condition. Although a vascular origin has been postulated, heterozygous missense variants in DHX37 have been attributed to the phenotype as well. How these various etiologies impact the clinical phenotype, gonadal histology and outcome of BTR remains unclear. STUDY DESIGN, SIZE, DURATION: For this cross-sectional study, individuals with BTR were recruited in eight Belgian pediatric endocrinology departments, between December 2019 and December 2022. A physical exam was performed cross-sectionally in all 17 end-pubertal participants and a quality of care questionnaire was completed by 11 of them. Exome-based panel testing of 241 genes involved in gonadal development and spermatogenesis was performed along with a retrospective analysis of presentation and management. A centralized histological review of gonadal rests was done for 10 participants. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 35 participants (33 with male, 1 with female, and 1 with non-binary gender identity) were recruited at a mean age of 15.0 ± 5.7 years. MAIN RESULTS AND THE ROLE OF CHANCE: The median age at presentation was 1.2 years [0-14 years]. Maternal gestational complications were common (38.2%), with a notably high incidence of monozygotic twin pregnancies (8.8%). Heterozygous (likely) pathogenic missense variants in DHX37 (p.Arg334Trp and p.Arg308Gln) were found in three participants. No other (likely) pathogenic variants were found. All three participants with a DHX37 variant had a microphallus at birth (leading to female sex assignment in one), while only six of the remaining 31 participants without a DHX37 variant (19.4%) had a microphallus at birth (information regarding one participant was missing). Testosterone therapy during infancy to increase penile growth was more effective in those without versus those with a DHX37 variant. The three participants with a DHX37 variant developed a male, female, and non-binary gender identity, respectively; all other participants identified as males. TRT in incremental doses had been initiated in 25 participants (median age at start was 12.4 years). Final height was within the target height range in all end-pubertal participants; however, 5 out of 11 participants (45.5%), for whom stretched penile length (SPL) was measured, had a micropenis (mean adult SPL: 9.6 ± 2.5). Of the 11 participants who completed the questionnaire, five (45.5%) reported suboptimal understanding of the goals and effects of TRT at the time of puberty induction. Furthermore, only 6 (54.5%) and 5 (45.5%) of these 11 participants indicated that they were well informed about the risks and potential side effects of TRT, respectively. Histological analysis of two participants with DHX37 variants suggested early disruption of gonadal development due to the presence of Müllerian remnants in both and undifferentiated gonadal tissue in one. In eight other analyzed participants, no gonadal remnants were found, in line with the BTR diagnosis. LIMITATIONS, REASONS FOR CAUTION: The limitations of this study include the relatively small sample size (n = 35) and the few individuals with DHX37 variants (n = 3). Furthermore, data on the SPL were often missing, due to this being undocumented or refused by participants. WIDER IMPLICATIONS OF THE FINDINGS: TRT provides adequate statural growth, even when initiated in late adolescence, thus providing time for physicians to explore the patients' gender identity if needed. However, sufficient and understandable information regarding the effects and side effects of TRT is required throughout the management of these patients. SPL remains suboptimal in many individuals and could be improved by TRT during infancy to mimic the physiological mini-puberty. An environmental origin in some participants is supported by the high incidence of gestational complications (38.2%) and by the three monozygotic twin pregnancies discordant for the BTR phenotype. Individuals with a heterozygous DHX37 variant have a more severe phenotype with severely restricted penile growth until adulthood. Histological analysis confirmed DHX37 as a gonadal development, rather than a BTR-related, gene. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by the Belgian Society for Pediatric Endocrinology and Diabetology (BESPEED) and by Ghent University Hospital under the NucleUZ Grant (E.D.B.). M.C. and E.D.B. are supported by an FWO senior clinical investigator grant (1801018N and 1802220N, respectively). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Blood transcriptomics to facilitate diagnosis and stratification in pediatric rheumatic diseases - a proof of concept study.

Transcriptome profiling of blood cells is an efficient tool to study the gene expression signatures of rheumatic diseases. This study aims to improve the early diagnosis of pediatric rheumatic diseases by investigating patients' blood gene expression and applying machine learning on the transcriptome data to develop predictive models. RNA sequencing was performed on whole blood collected from children with rheumatic diseases. Random Forest classification models were developed based on the transcriptome data of 48 rheumatic patients, 46 children with viral infection, and 35 controls to classify different disease groups. The performance of these classifiers was evaluated by leave-one-out cross-validation. Analyses of differentially expressed genes (DEG), gene ontology (GO), and interferon-stimulated gene (ISG) score were also conducted. Our first classifier could differentiate pediatric rheumatic patients from controls and infection cases with high area-under-the-curve (AUC) values (AUC = 0.8 ± 0.1 and 0.7 ± 0.1, respectively). Three other classifiers could distinguish chronic recurrent multifocal osteomyelitis (CRMO), juvenile idiopathic arthritis (JIA), and interferonopathies (IFN) from control and infection cases with AUC ≥ 0.8. DEG and GO analyses reveal that the pathophysiology of CRMO, IFN, and JIA involves innate immune responses including myeloid leukocyte and granulocyte activation, neutrophil activation and degranulation. IFN is specifically mediated by antibacterial and antifungal defense responses, CRMO by cellular response to cytokine, and JIA by cellular response to chemical stimulus. IFN patients particularly had the highest mean ISG score among all disease groups. Our data show that blood transcriptomics combined with machine learning is a promising diagnostic tool for pediatric rheumatic diseases and may assist physicians in making data-driven and patient-specific decisions in clinical practice

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified &gt;300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection