Helsinki Children's Hospital

Twice-daily toothbrushing and flossing are standard oral hygiene practices, yet up to 50% of plaque may remain even with proper technique. The home-use dual-light antibacterial photodynamic therapy (aPDT), consisting of 405 and 810 nm light, used together with indocyanine green photosensitizer, has emerged as a promising method to enhance plaque control. This study evaluated the efficacy of adjunctive daily ten-minute dual-light aPDT treatment in reducing dental plaque among healthy adults. Thirty young healthy adults were randomly assigned to two groups in a six-week crossover design. Group 1 received two weeks of daily dual-light aPDT alongside conventional oral care, while Group 2 continued their regular oral care. After a two-week crossover phase, groups switched interventions. Plaque levels were measured at four time points using the Greene-Vermillion index. At baseline, less plaque was observed in Group 1 (median [IQR] 1.0 [0.75-1-5]) than in Group 2 (1.0 [1.0-1.5]) (p = 0.026). After the first treatment phase, both Group 1 and Group 2 improved their oral hygiene 0.75 [0.5-1-0] (-28.4%) and 1.0 [0.5-1.25] (-24.1%), p<0.0001 and p<0.0001, respectively. During the second treatment phase, Group 2, which was now using aPDT, demonstrated a significant plaque reduction from 1.125 [0.94-1.5] to 0.75 [0.5-1.25] (-14.1%) (p = 0.011), whereas Group 1 with standard treatment showed no statistical change, from 0.5 [0.44-0-81] to 0.63 [0.5-1.19] (+22.4) (p=0.11). Pooled analysis revealed that the adjunct dual-light aPDT significantly reduced plaque compared to baseline, from 1.0 [1.0-1.5] to 0.5 [0.5-1.0] (-21.2%)(p=0.0001), while conventional care alone showed no significant change from 1.0 [0.5-1.5] to 1.0 [0.5-1.5] (-6.5%) (p=0.11). Daily use of dual-light aPDT as an adjunct to self-care significantly enhances plaque control beyond conventional toothbrushing and flossing, offering a potentially effective, non-invasive preventive strategy for maintaining oral hygiene in healthy adults. This study shows that dual-light aPDT can serve as a clinically relevant adjunct to daily oral home care, enhancing plaque control even in individuals with good oral hygiene. It may be beneficial for patients with increased plaque-retentive challenges, including orthodontic appliances, implants, fixed prostheses, or reduced manual dexterity.

Disease control in AYAs with chronic conditions remained stable throughout the transition to adult healthcare. Psychiatric comorbidity is an important contributor to inferior disease control and HRQoL across the transfer of care.Trial registration:Registration name, "The Bridge"; registration number, NCT04631965 ( https://clinicaltrials.gov/ct2/show/NCT04631965 ). • The transfer of care from pediatric to adult healthcare has been associated with declines in health outcomes among adolescents and young adults with chronic conditions. • Psychiatric comorbidity may complicate the transition to adult healthcare. • Disease control, health-related quality of life, and experiences of care are good in most AYAs after the transfer of care to adult healthcare. • Mental well-being likely plays a more crucial and complex role in the transition to adult care than currently understood.

Primary osteoporosis can be caused by pathogenic variants in multiple genes. Recently, rare heterozygous variants in SGMS2, encoding SGMS2, have been identified to cause early-onset osteoporosis or more severe skeletal dysplasia. The incidence of pathogenic SGMS2 variants and their consequent clinical features, however, remain limited. This study aimed to identify the prevalence and nature of SGMS2 variants in Finnish patients with genetically undiagnosed idiopathic early-onset osteoporosis. All eleven exons and exon-intron boundaries of SGMS2 were sequenced. In a cohort of 44 patients (42 females and two males, median age at the time of recruitment 60 years, range 25-76 years), we identified one rare heterozygous missense variant (c.715T>C, p.Phe239Leu) and three intronic variants with unknown functional consequences; no pathogenic or likely pathogenic variants were found. Our results suggest that pathogenic variants in SGMS2 are not a common cause of early-onset idiopathic osteoporosis in Finnish patients. Further studies in larger cohorts and variable skeletal phenotypes are needed to increase our understanding of the role of SGMS2 in skeletal fragility.

To evaluate the concurrent validity of assessing infants' gross motor performance with an at-home wearable measurement versus the Alberta Infant Motor Scale (AIMS). This observational study used a new multi-sensor wearable Motor Assessment of Infants with a JUmpsuit (MAIJU) for 67 at-home measurements of 42 infants (60% males; mean age 11.5 months, SD 3.7 months, range 4-18 months). The study collates a normative cohort of typically developing volunteers (n=17, 65% males; 27 measurements, mean age 11.8 months, SD 3.1 months, range 7-18 months) and a clinical cohort recruited from a neurodevelopmental follow-up clinic (n=25, 56% males; mean age 11.2 months, SD 3.8 months, range 4-17 months). We correlated the expert-assessed total AIMS score to a holistic assessment of motor development (the BABA Infant Motor Score [BIMS]) from the MAIJU measurements. Additionally, detailed MAIJU-derived metrics were compared to the AIMS scores, to train machine learning-based AIMS predictions. There was a very strong correlation (Spearman's rank correlation coefficient [rho]=0.97, p < 10-40) between BIMS and AIMS. Centile-based detection of low-performing individuals (cut-offs of 5% and 10%) showed high agreement between AIMS and BIMS (Cohen's kappa=0.81). Performance of a machine learning-based AIMS prediction from the wearable data was comparable (rho=0.96, p < 10-37) to direct use of the BIMS score. Assessing motor performance with scalable, at-home wearable measurements is highly comparable to the widely used AIMS assessment. An objective, quantitative, and expert-independent motor assessment holds promise for providing benchmarks in geographically distributed health care or clinical trials.

Osteogenesis imperfecta is a rare hereditary condition affecting type 1 collagen formation. Among the wide spectrum of phenotypic features, osteogenesis imperfecta variably impairs craniofacial growth, affecting facial morphology and predisposing to malocclusion. At present, bisphosphonates are the gold standard for treatment of osteogenesis imperfecta, but knowledge on the effect of the medication on craniofacial growth is lacking. This retrospective study analysed lateral skull radiographs of 36 growing individuals with osteogenesis imperfecta and bisphosphonate treatment history (mean age 10.0 years, 13 females). Of them, 23 had been diagnosed with type I, 8 with type III, and 5 with type IV osteogenesis imperfecta. The historical control group that had not received bisphosphonate therapy comprised 34 individuals (mean age 8.1 years, 22 females) with osteogenesis imperfecta, type I in 18, type III in 7, and type IV in 9 individuals. The cephalometric measurement values were converted into age- and sex-matched Z-scores based on normal population values of the same ethnicity. Inter-group comparisons of the Z-scores showed several statistically significant differences where the bisphosphonate treatment group deviated less from unaffected population than the historical group. These included one or more of the mandibular size measurements in all studied types of osteogenesis imperfecta, anterior facial height and maxillary length in type IV, as well as cranial base angle, posterior facial height and angulation between the jaws in type III. Our findings suggest that bisphosphonate therapy may positively enhance both mid-facial and mandibular craniofacial growth in individuals with osteogenesis imperfecta.

ABSTRACTThe human gut microbiota is central to the health and development of the host, and the early-life microbiota is affected by a range of factors that can alter the infant's development for years to come. The role of the external, natural environment in shaping the gut microbiota is still largely unknown. We examined how the environment surrounding the home postnatally is associated with the infant gut microbiota in the first 2 y of life. The study utilized 16 s rRNA data from 893 children's fecal samples from the longitudinal birth cohort HELMi. We show that the environment has a minimal overall association with microbiota development (R2 < 1%). Air quality explained the greatest degree of variation in microbiota composition, while only forests, agriculture and inland wetlands near the home had any significant association with bacterial genera. The results suggest that the infant gut microbiota is not strongly dependent on the external natural environment, and that the impact of the environment is mostly due to exposure to air pollution that may affect the host's immune system and indirectly the gut microbiota.

Transplantations of cryopreserved immature testicular tissue (ITT) or spermatogonial stem cells (SSCs) represent promising approaches to restore fertility in patients with testicular tissue or cell suspension cryopreserved for fertility preservation. With over 3000 testicular samples cryopreserved globally, clinically viable and standardized protocols restoring fertility using cryopreserved testicular tissue/cells are urgently needed. Decades of research demonstrate the feasibility of immature testicular tissue transplantation (ITTT) or spermatogonial stem cell transplantation (SSCT) in animal models, including non-human primates. However, significant challenges remain in translating these options to human clinical practice. Critical factors include rigorous patient selection, robust pre-transplant evaluations to mitigate risks of malignant cell reintroduction, and the optimization of transplantation timing to support spermatogenesis. Developing comprehensive follow-up protocols and international data-sharing frameworks is essential to optimize outcomes. While offering the potential for genetic parenthood and enhanced quality of life for cancer survivors, these techniques require further refinement to ensure safety, efficacy, and realistic expectations. This paper outlines the framework for advancing the clinical translation of autotransplantation of testicular tissue/cells through collaboration and innovation.

IntroductionResearch indicates that the sexual support needs of patients with anorectal malformations (ARM) and Hirschsprung disease (HD) are often not addressed by patients, parents, and healthcare professionals (HPs) in their interactions. An international support website was developed to empower stakeholders, by addressing identified barriers. This study aimed to explore the empowerment potential of this disease-specific tool.Materials and MethodsTwo online surveys were disseminated between May 1 and October 1, 2023; one for HPs and another for patients/parents. The surveys sought to assess and understand the website's expected empowerment effect. Empowerment was conceptualized using patient/professional empowerment models. Data were descriptively analyzed.ResultsA total of 12 patients (ARM,n = 11; HD,n = 1), 17 parents (ARM,n = 9; HD,n = 8), and 20 HPs responded to the survey. HPs largely expected the website to have a positive empowerment effect, by providing a sense of meaning, information, support, and opportunities to learn and grow. Less of an effect was expected for “freeing up resources.” For patients and parents, an empowerment effect was also expected, by generating the knowledge, skills, attitudes, and self-awareness necessary to influence their own behavior and by providing a sense of meaning and coherence. Respondents experienced the website positively, yet one patient and one parent considered the website “fully complete.” Inclusivity, cultural sensitivity, and accessibility were highlighted as focus points.ConclusionTo increase the website's empowerment potential, attention should be paid to inclusivity, cultural sensitivity, and accessibility, as well as its implementation within the (institutional) contexts where patients, parents, and HPs interact.

Ex vivo drug response profiling is emerging as a valuable tool for identifying drug resistance mechanisms and advancing precision medicine in hematological cancers. However, the functional impact of dysregulation of the epigenome and transcriptome in this context remains poorly understood. In this study, we combined ex vivo drug sensitivity profiling with transcriptomic and epigenomic analyses in diagnostic samples from 597 pediatric B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) patients. Ex vivo resistance to antimetabolites (e.g., cytarabine, thioguanine), glucocorticoids (e.g., dexamethasone, prednisolone), and doxorubicin was independently associated with reduced relapse‐free survival (P < 0.05). Molecular profiling identified pretreatment DNA methylation and gene expression patterns distinguishing resistant from sensitive cases, revealing key drug resistance signatures. These included aberrant expression of genes related to heme metabolism (e.g., ATPV06A) and KRAS signaling (e.g., GS02). Notably, we also observed atypical expression of genes usually restricted to T cells and other immune cells (e.g., ITK) in resistant BCP‐ALL cells. Our findings demonstrate that ex vivo drug response patterns are predictive of clinical outcomes and reflect intrinsic molecular states associated with drug tolerance. This integrative multi‐omics approach highlights potential therapeutic targets and underscores the value of functional precision medicine in identifying treatment vulnerabilities in pediatric ALL.

There are only a few studies on physical fitness in pediatric inflammatory bowel disease (PIBD). We compared physical fitness in PIBD patients versus healthy controls and analyzed the role of contributing disease- and patient-related factors. This cross-sectional study included 73 patients with PIBD aged 13.0 (2.8) (mean [standard deviation]) years from two Finnish university hospitals, 31 with Crohn's disease and 42 with ulcerative or unclassified colitis, and 74 age- and sex-matched controls. Cardiorespiratory and neuromuscular fitness were assessed, physical activity (PA) was measured, and disease characteristics concerning physical fitness were analyzed. Cardiorespiratory fitness, that is, maximal workload (Wmax/kg) and peak oxygen uptake (VO2peak/kg) were lower in patients with PIBD than in controls: Wmax/kg 3.01 (0.72) versus 3.29 (0.57) W/kg, p = 0.007; VO2peak/kg 38.3 (8.5) versus 46.9 (7.4) mL/kg/min, p < 0.001, respectively. Neuromuscular fitness, as evaluated using sit-up, standing long jump, grip strength, and shuttle run tests, was lower in patients compared with controls. Disease activity, severity, and duration, or PA, were not related to Wmax/kg and VO2peak/kg in univariate analysis. However, in multivariate analysis, the use of biological medications was associated positively, and higher age- and sex-adjusted body mass index for children and adolescents was associated negatively with Wmax/kg and VO2peak/kg. Patients with PIBD had lower physical fitness than age- and sex-matched controls. The causes of lower physical fitness in PIBD are likely complex, warranting the need for longitudinal studies examining the associations of factors like body composition, visceral fat, and control of disease severity with physical fitness.