Three-dimensional view of microglia-amyloid plaque interactions.

Recent gene expression studies have revealed about 10 different states of microglia, some of which are characteristic for Alzheimer-like amyloid plaque pathology. However, it is not presently known how these translate into morphological features that would reflect microglia interaction with amyloid plaques. With optimized conditions for confocal microscopy in amyloid plaque forming APP/PS1 transgenic mice we reveal new details of how microglia processes interact with amyloid plaques.

RFX6 haploinsufficiency predisposes to diabetes through impaired beta cell function.

Aims/hypothesis: Regulatory factor X 6 (RFX6) is crucial for pancreatic endocrine development and differentiation. The RFX6 variant p.His293LeufsTer7 is significantly enriched in the Finnish population, with almost 1:250 individuals as a carrier.

Prenatal, newborn and childhood factors and the timing of puberty in boys and girls.

Background: Our aim was to determine if prenatal factors, gestational age, birth weight and length, and childhood body mass index (BMI) are associated with the timing of puberty.

Methods: Our population-based study comprised 4826 girls and 5112 boys born between 1997 and 2002. Multiple linear regression modeled the relationships between the maternal and child predictors and the age at peak height velocity (PHV).

Central precocious puberty in boys: secular trend and clinical features.

Objective: Recent studies suggest that boys enter puberty at a younger age, and the incidence of male central precocious puberty (CPP) is increasing. In this study, we explore the incidence of male CPP and identify key clinical and auxological indicators for organic CPP (OCPP).

Design: A retrospective registry-based study.

During an 18-month course of automated insulin delivery treatment, children aged 2 to 6 years achieve and maintain a higher time in tight range.

Aims: To investigate whether the positive effects on glycaemic outcomes of 3-month automated insulin delivery (AID) achieved in 2- to 6-year-old children endure over an extended duration and how AID treatment affects time in tight range (TITR), defined as 3.9-7.8 mmol/L.

Health-related quality of life and self-reported health status in adolescents with chronic health conditions before transfer of care to adult health care: an international cohort study.

Background: Heath-related quality of life (HRQoL) is lower in adolescents with chronic health conditions compared to healthy peers. While there is evidence of some differences according to the underlying condition and gender, differences by measure and country are poorly understood. In this study we focus on the differences in HRQoL in adolescents with various chronic medical conditions in the year before transfer of care to adult health services.

Mechanisms of thyrotropin receptor-mediated phenotype variability deciphered by gene mutations and M453T-knockin model.

The clinical spectrum of thyrotropin receptor-mediated (TSHR-mediated) diseases varies from loss-of-function mutations causing congenital hypothyroidism to constitutively active mutations (CAMs) leading to nonautoimmune hyperthyroidism (NAH). Variation at the TSHR locus has also been associated with altered lipid and bone metabolism and autoimmune thyroid diseases. However, the extrathyroidal roles of TSHR and the mechanisms underlying phenotypic variability among TSHR-mediated diseases remain unclear.

Congenital hypogonadotropic hypogonadism in a patient with a de novo POGZ mutation.

Objective: Congenital hypogonadotropic hypogonadism (CHH) is a rare, genetically heterogeneous reproductive disorder caused by gonadotropin-releasing hormone (GnRH) deficiency. Approximately half of CHH patients also have decreased or absent sense of smell, that is, Kallmann syndrome (KS). We describe a patient with White-Sutton syndrome (developmental delay and autism spectrum disorder) and KS due to a heterozygous de novo mutation in POGZ (c.

Residual insulin secretion in individuals with type 1 diabetes in Finland: longitudinal and cross-sectional analyses.

Background: Contrary to the presumption that type 1 diabetes leads to an absolute insulin deficiency, many individuals with type 1 diabetes have circulating C-peptide years after the diagnosis. We studied factors affecting random serum C-peptide concentration in individuals with type 1 diabetes and the association with diabetic complications.

Methods: Our longitudinal analysis included individuals newly diagnosed with type 1 diabetes from Helsinki University Hospital (Helsinki, Finland) with repeated random serum C-peptide and concomitant glucose measurements from within 3 months of diagnosis and at least once later.

Most dystrophic neurites in the common 5xFAD Alzheimer mouse model originate from axon terminals.

How dystrophic neurites form around amyloid plaques is a key aspect of understanding the early pathophysiology of Alzheimer's disease. At present, three hypotheses prevail: (1) dystrophies result from extracellular amyloid-beta (Aβ) toxicity; (2) dystrophies results from accumulation of Aβ into distal neurites; and (3) dystrophies represent blebbing of the somatic membrane of a neuron with high Aβ load. We utilized a unique feature of the common 5xFAD AD mouse model to test these hypotheses.

Pancreatic imaging in MEN1-comparison of conventional and somatostatin receptor positron emission tomography/computed tomography imaging in real-life setting.

Objective: Pancreatic neuroendocrine tumors (panNETs) are the leading cause of death in patients with multiple endocrine neoplasia type 1 (MEN1). The role of somatostatin receptor positron emission tomography/computed tomography (SSTR PET/CT) in MEN1 has not been established. The aim was to assess pancreatic imaging in MEN1 in a real-life setting.

Disease control and psychiatric comorbidity among adolescents with chronic medical conditions: a single-centre retrospective study.

Background: To investigate disease control, psychiatric comorbidity, substance use and their possible associations in adolescents with chronic medical conditions before transfer to adult healthcare.

Methods: We collected clinical data from the year preceding transfer of care and psychiatric data from the records of the paediatric hospital in Helsinki, Finland (population base 1.7 million).

MiniMed 780G™ in 2- to 6-Year-Old Children: Safety and Clinical Outcomes After the First 12 Weeks.

The safety and impact of the advanced hybrid closed-loop (AHCL) system on glycemic outcome in 2- to 6-year-old children with type 1 diabetes and the diabetes distress of caregivers were evaluated. This was an open-label prospective study ( = 35) with historical controls matched by treatment unit, diabetes duration, age, gender, and baseline treatment modality. The inclusion criteria were (1) type 1 diabetes diagnosis >6 months, (2) total daily dose of insulin ≥8 U/day, (3) HbA1c <10% (85 mmol/mol), and (4) capability to use insulin pump and continuous glucose monitoring.

Identification of monogenic variants in more than ten per cent of children without type 1 diabetes-related autoantibodies at diagnosis in the Finnish Pediatric Diabetes Register.

Aims/hypothesis: Monogenic forms of diabetes (MODY, neonatal diabetes mellitus and syndromic forms) are rare, and affected individuals may be misclassified and treated suboptimally. The prevalence of type 1 diabetes is high in Finnish children but systematic screening for monogenic diabetes has not been conducted. We assessed the prevalence and clinical manifestations of monogenic diabetes in children initially registered with type 1 diabetes in the Finnish Pediatric Diabetes Register (FPDR) but who had no type 1 diabetes-related autoantibodies (AABs) or had only low-titre islet cell autoantibodies (ICAs) at diagnosis.

Timing of puberty and school performance: A population-based study.

Objective: To determine whether the timing of puberty associates with school performance.

Methods: Growth data on 13,183 children born between 1997 and 2002, were collected from child health clinics and school healthcare and school performance data from school records. Age at peak height velocity (PHV) marked pubertal timing.

Presentation and diagnosis of childhood-onset combined pituitary hormone deficiency: A single center experience from over 30 years.

Background: Childhood-onset combined pituitary hormone deficiency (CPHD) has a wide spectrum of etiologies and genetic causes for congenital disease. We aimed to describe the clinical spectrum and genetic etiologies of CPHD in a single tertiary center and estimate the population-level incidence of congenital CPHD.

Methods: The retrospective clinical cohort comprised 124 CPHD patients (48 with congenital CPHD) treated at the Helsinki University Hospital (HUH) Children's Hospital between 1985 and 2018.

The Effectiveness of Unilateral Cochlear Implantation on Performance-Based and Patient-Reported Outcome Measures in Finnish Recipients.

Understanding speech is essential for adequate social interaction, and its functioning affects health, wellbeing, and quality of life (QoL). Untreated hearing loss (HL) is associated with reduced social activity, depression and cognitive decline. Severe and profound HL is routinely rehabilitated with cochlear implantation.

Circulating Liver-enriched Antimicrobial Peptide-2 Decreases During Male Puberty.

Context: Circulating levels of liver-enriched antimicrobial peptide 2 (LEAP2), a ghrelin receptor antagonist, decrease under caloric restriction and increase in obesity. The role of LEAP2 in male puberty, a phase with accelerated energy demand, is unclear.

Objective: This work aimed to investigate whether circulating LEAP2 levels are downregulated in boys following the onset of puberty to respond to the energy need required for growth.

The effect of COVID-19 lockdown on the glycemic control of children with type 1 diabetes.

Background: Between March 18 and May 13 2020, the COVID-19 pandemic outbreak in Finland resulted in the closure of schools and the limitation of daycare (i.e. lockdown).

A multigenerational study on phenotypic consequences of the most common causal variant of HNF1A-MODY.

Aims/hypothesis: Systematic studies on the phenotypic consequences of variants causal of HNF1A-MODY are rare. Our aim was to assess the phenotype of carriers of a single HNF1A variant and genetic and clinical factors affecting the clinical spectrum.

Methods: We conducted a family-based multigenerational study by comparing heterozygous carriers of the HNF1A p.

Gut microbiota develop towards an adult profile in a sex-specific manner during puberty.

Accumulating evidence indicates that gut microbiota may regulate sex-hormone levels in the host, with effects on reproductive health. Very little is known about the development of intestinal microbiota during puberty in humans. To assess the connection between pubertal timing and fecal microbiota, and to assess how fecal microbiota develop during puberty in comparison with adult microbiota, we utilized a Finnish allergy-prevention-trial cohort (Flora).

The aetiology of extreme tall stature in a screened Finnish paediatric population.

Background: Extremely tall children (defined as height SDS (HSDS) ≥+3) are frequently referred to specialized healthcare for diagnostic work-up. However, no systematic studies focusing on such children currently exist. We investigated the aetiology, clinical features, and auxological clues indicative of syndromic tall stature in extremely tall children subject to population-wide growth monitoring and screening rules.