Trait-like characteristics of the sleep EEG across adolescent development

Waking and sleep data in adults show high heritability and trait-like characteristics in EEG spectra. This phenomenon has not been examined in children and adolescents where brain development influences the EEG. The present study examines whether a trait-like sleep EEG pattern is detectable across adolescent development. Two consecutive nights of standard sleep recordings were performed in 19 9-10-year-old children and 26 15-16-year-old teens, and were repeated 1.5-3 years later. EEG spectra averaged across the night for non-rapid eye movement and rapid eye movement sleep separately were classified using hierarchical cluster analysis, which showed that all 4 nights of a participant clustered together for a majority of participants. Intraclass correlation coefficients were also very high (>0.7) across nights separated by several years, indicating a trait-like feature of the sleep EEG. In summary, our results, using two measures of stability, indicate that a "trait-like" aspect can be detected in the sleep EEG across adolescent development despite considerable neurodevelopmental changes. This finding indicates that the brain oscillators responsible for generating the sleep EEG signal remain relatively stable across adolescent development

Clinical case seminar - Hypogonadotropic hypogonadism as a presenting feature of late-onset X-linked adrenal hypoplasia congenita

Mutations in the orphan nuclear receptor DAX-1 cause X-linked adrenal hypoplasia congenita. Affected boys usually present with primary adrenal failure in early infancy or childhood. Impaired sexual development because of hypogonadotropic hypogonadism becomes apparent at the time of puberty. We report adult-onset adrenal hypoplasia congenita in a patient who presented with hypogonadism at 28 yr of age. Although he had no clinical evidence of adrenal dysfunction, compensated primary adrenal failure was diagnosed by biochemical testing. Semen analysis showed azoospermia, and he did not achieve fertility after 8 months of treatment with gonadotropins. A novel Y380D DAX-1 missense mutation, which causes partial loss of function in transient gene expression assays, was found in this patient. This case demonstrates that partial loss-of-function mutations in DAX1 can present with hypogonadotropic hypogonadism and covert adrenal failure in adulthood. Further, an important role for DAX-1 in spermatogenesis in humans is confirmed, supporting findings in the Dax1 (Ahch) knockout mouse

Wound fluid ceftriaxone concentrations after local application with calcium sulphate as carrier material in the treatment of orthopaedic device-associated hip infections.

There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO <sub>4</sub> ) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO <sub>4</sub> applied locally to treat ODAI. A total of 30 operations with ceftriaxone-loaded CaSO <sub>4</sub> had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). A total of 37 wound fluid concentrations from 16 operations performed in 14 patients were collected. The ceftriaxone concentrations remained approximately within a range of 100 to 200 mg/l up to three weeks. The median concentration was 108.9 mg/l (interquartile range 98.8 to 142.5) within the first ten days. No systemic adverse reactions were observed. Our study highlights new clinical data of locally administered ceftriaxone with CaSO <sub>4</sub> as carrier material. The near-constant release of ceftriaxone from CaSO <sub>4</sub> observed in vitro could be confirmed in vivo. The concentrations remained below known local toxicity thresholds.Cite this article: Bone Joint Res 2022;11(11):835-842

New Technologies for the Identification of Novel Genetic Markers of Disorders of Sex Development (DSD)

Although the genetic basis of human sexual determination and differentiation has advanced considerably in recent years, the fact remains that in most subjects with disorders of sex development (DSD) the underlying genetic cause is unknown. Where pathogenic mutations have been identified, the phenotype can be highly variable, even within families, suggesting that other genetic variants are influencing the expression of the phenotype. This situation is likely to change, as more powerful and affordable tools become widely available for detailed genetic analyses. Here, we describe recent advances in comparative genomic hybridisation, sequencing by hybridisation and next generation sequencing, and we describe how these technologies will have an impact on our understanding of the genetic causes of DSD

Perioperative Antibiotikaprophylaxe bei elektiver Gelenkprothesenimplantation

Eine Gelenkprotheseninfektion ist eine schwerwiegende Komplikation, die nach einer Gelenkprothesenimplantation auftreten kann. Zu den Präventionsmassnahmen einer Infektion gehört eine Palette von Massnahmen wie zum Beispiel prä- und postoperative Checklisten, sorgfältige Operationspräparation, Haarentfernung und Hautdesinfektion, strikte Hygienemassnahmen, eine gute chirurgische Technik mit ­kurzer Operationsdauer, postoperativ Entfernen von Urinkatheter und eine korrekte Wundpflege nach Operation. Eine systemische präoperative Antibiotikaprophylaxe (AMP) ist ein Faktor, der zu diesen zahlreichen Präventionsmassnahmen gehört. SWISSNOSO veröffentlichte Richtlinien zu Verantwortlichkeiten und Ablauf der Verabreichung der AMP in den Jahren 2015 [1] und 2018 [2]. Deren Empfehlungen für den Fachbereich Orthopädie und Traumatologie des Bewegungsapparates sind in den Tabellen 1a und 1b wiedergegeben

Testosterone production during puberty in two 46,XY patients with disorders of sex development and novel NR5A1 (SF-1) mutations

BACKGROUND: Steroidogenic factor 1 (SF-1, NR5A1) is a key transcriptional regulator of many genes involved in the hypothalamic–pituitary–gonadal axis and mutations in NR5A1 can result in 46,XY disorders of sex development (DSD). Patients with this condition typically present with ambiguous genitalia, partial gonadal dysgenesis, and absent/rudimentary Müllerian structures. In these cases, testosterone is usually low in early infancy, indicating significantly impaired androgen synthesis. Further, Sertoli cell dysfunction is seen (low inhibin B, anti-Müllerian hormone). However, gonadal function at puberty in patients with NR5A1 mutations is unknown. SUBJECTS AND METHODS: Clinical assessment, endocrine evaluation, and genetic analysis were performed in one female and one male with 46,XY DSD who showed spontaneous virilization during puberty. The female patient presented at adolescence with clitoral hypertrophy, whereas the male patient presented at birth with severe hypospadias and entered puberty spontaneously. Molecular analysis of NR5A1 was performed followed by in vitro functional analysis of the two novel mutations detected. RESULTS: Testosterone levels were normal during puberty in both patients. Analysis of NR5A1 revealed two novel heterozygous missense mutations in the ligand-binding domain of SF-1 (patient 1: p.L376F; patient 2: p.G328V). The mutant proteins showed reduced transactivation of the CYP11A promoter in vitro. CONCLUSION: Patients with 46,XY DSD and NR5A1 mutations can produce sufficient testosterone for spontaneous virilization during puberty. Phenotypic females (46,XY) with NR5A1 mutations can present with clitoromegaly at puberty, a phenotype similar to other partial defects of androgen synthesis or action. Testosterone production in 46,XY males with NR5A1 mutations can be sufficient for virilization at puberty. As progressive gonadal dysgenesis is likely, gonadal function should be monitored in adolescence and adulthood, and early sperm cryopreservation considered in male patients if possible

Goal-Directed Personalized Upper Limb Intensive Therapy (PULIT) for Children With Hemiparesis: A Retrospective Analysis

Importance: Children with hemiparesis experience limitations in activities of daily living (ADLs) as a result of upper limb impairments. To address these limitations, we developed a group-based Personalized Upper Limb Intensive Therapy (PULIT) program combining modified constraint-induced movement therapy, bimanual intensive therapy, and exergame-based robotics. Objective: To determine the effectiveness of PULIT in helping children with upper limb impairments achieve individually set goals and enable transfer of the attained motor skills into ADLs. Design: Retrospective analysis. Setting: Day camp at a pediatric rehabilitation clinic in Switzerland. Participants: Twenty-three children with upper limb impairment (unilateral cerebral palsy, n = 16; acquired brain injury, n = 7); 13 boys and 10 girls (M age = 7 yr, 8 mo, SD = 2 yr, 1 mo; Manual Ability Classification System Level I-IV). Intervention: Thirty hours of PULIT over the course of 8 days. Outcomes and measures: Goal attainment scaling (GAS) was assessed on the first and last day of intervention. The Canadian Occupational Performance Measure (COPM) and dexterity tests, such as the Box and Block Test (BBT), were administered 3 wk before and 3 wk after the intervention. Results: Total goal achievement was 85.7%. GAS, parent- and child-rated COPM Performance and Satisfaction, and the BBT of the affected and dominant upper limb improved significantly. Conclusions and relevance: PULIT effectively increases children's dexterity of the impaired and dominant upper limb, improves ADL performance, and achieves individual goals. This retrospective analysis could serve as a basis for a future randomized trial. What This Article Adds: This article informs occupational therapy practitioners about a therapy program that includes conventional and rehabilitation technology interventions and enables children with hemiparesis of the upper limb to improve relevant ADL tasks in 8 days' time

Effective Biofilm Eradication on Orthopedic Implants with Methylene Blue Based Antimicrobial Photodynamic Therapy In Vitro

Periprosthetic joint infections (PJI) are difficult to treat due to biofilm formation on implant surfaces, often requiring removal or exchange of prostheses along with long-lasting antibiotic treatment. This in vitro study investigated the effect of methylene blue photodynamic therapy (MB-PDT) on PJI-causing biofilms on different implant materials. MB-PDT (664 nm LED, 15 J/cm2) was tested on different Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Cutibacterium acnes strains in both planktonic form and grown in early and mature biofilms on prosthetic materials (polyethylene, titanium alloys, cobalt–chrome-based alloys, and bone cement). The minimum bactericidal concentration with 100% killing (MBC100%) was determined. Chemical and topographical alterations were investigated on the prosthesis surfaces after MB-PDT. Results showed a MBC100% of 0.5–5 μg/mL for planktonic bacteria and 50–100 μg/mL for bacteria in biofilms—independent of the tested strain, the orthopedic material, or the maturity of the biofilm. Material testing showed no relevant surface modification. MB-PDT effectively eradicated common PJI pathogens on arthroplasty materials without damage to the materials, suggesting that MB-PDT could be used as a novel treatment method, replacing current, more invasive approaches and potentially shortening the antibiotic treatment in PJI. This would improve quality of life and reduce morbidity, mortality, and high health-care costs

Fast and Sensitive Multiplex Real-Time Quantitative PCR to Detect Cutibacterium Periprosthetic Joint Infections

Diagnosis of Cutibacterium periprosthetic joint infections (PJIs) is challenging due to a long cultivation time of up to 14 days. Faster culture-independent diagnosis would improve patient care with early and accurate treatment. Specific primers and probes were designed for Cutibacterium acnes, Cutibacterium avidum, and Cutibacterium granulosum and evaluated in a multiplex TaqMan real-time quantitative PCR (qPCR) format on 57 skin swabs and 20 culture-negative cerebrospinal fluid samples. The multiplex qPCR was tested in a PJI cohort of 41 sonication fluid samples from removed implants infected with different pathogens. All five culture-positive Cutibacterium PJIs were detected with the corresponding Cutibacterium-specific probe (100% positive percent agreement). The multiplex qPCR additionally detected C. avidum in two PJI sonication fluid samples that were diagnosed as Staphylococcus species infections according to culture (95% negative percent agreement). The new multiplex qPCR can provide a Cutibacterium PJI diagnosis within 1 day, allowing early and accurate antibiotic treatment. A prospective diagnostic trial in PJI with a high number of Cutibacterium species infections (shoulder PJI) is needed for further evaluation