Reference Ranges and Determinants of Thyroid Function and TSH Receptor Antibodies During Early Pregnancy in Nepal.

Objective: Different definitions of thyroid dysfunction during pregnancy may lead to under or overtreatment. The aims of this study were to (1) define population-based pregnancy-specific reference ranges for thyroid dysfunction during early pregnancy in Nepal and assess the impact of antibody positivity, (2) quantify the diagnostic impact of population-based reference ranges compared with current practice and (3) assess the determinants of thyroid function and antibody positivity.

Methods: A total of 800 healthy pregnant women aged 20-40 years in the Bhaktapur municipality were included.

Modeling the acute mucosal toxicity to fractionated radiotherapy combined with the ATM inhibitor WSD0628.

ATM inhibitors are being developed as radiosensitizers to improve the antitumor effects of radiotherapy, but ATM inhibition can also radiosensitize normal tissues. Therefore, understanding the elevated risk for normal tissue toxicities is critical for radiosensitizer development. This study focused on modeling the relationship between acute mucosal toxicity, radiation dose, fractionation schedule, and radiosensitizer exposure.

DNA-PK inhibition shows differential radiosensitization in orthotopic GBM PDX models based on DDR pathway deficits.

Glioblastoma (GBM) remains one of the most therapy-resistant malignancies with frequent local failures despite aggressive surgery, chemotherapy, and ionizing radiation (IR). Small molecule inhibitors of DNA-dependent protein kinase (DNA-PKi's) are potent radiosensitizers currently in clinical trials. Determining which patients may benefit from radiosensitization with DNA-PKi's is critical to avoid unnecessary increased risk of normal tissue toxicity.

Breastfeeding and biomarkers of folate and cobalamin status in Norwegian infants: a cross-sectional study.

Folate and vitamin B (cobalamin) are essential for growth and development. This cross-sectional study aims to describe folate and vitamin B status according to infant age and breastfeeding practices in Norwegian infants. Infants aged 0-12 months ( = 125) were recruited through public health clinics.

Trend analyses of persistent organic pollutants in human milk from first-time mothers in Norway between 2002 and 2021.

Introduction: Persistent organic pollutants (POPs) are stable compounds characterized by their resistance to degradation. From the 1960-70's organochlorine pesticides (OCPs), such as DDTs and polychlorinated biphenyls (PCBs) raised concerns regarding health and environmental impacts. This has led to the banning of POPs in the USA and Europe including Norway in 1980 and worldwide under the 2004 Stockholm Convention.

Corticospinal excitability at rest outside of a task does not differ from task intertrial intervals in healthy adults.

Human corticospinal excitability (CSE) modulates during movement, when muscles are active, but also at rest, when muscles are not active. These changes in resting motor system excitability can be transient or longer lasting. Evidence from transcranial magnetic stimulation (TMS) studies suggests even relatively short periods of motor learning on the order of minutes can have lasting effects on resting CSE.

Aberrant ATM signaling and homology-directed DNA repair as a vulnerability of p53-mutant GBM to AZD1390-mediated radiosensitization.

ATM is a key mediator of radiation response, and pharmacological inhibition of ATM is a rational strategy to radiosensitize tumors. AZD1390 is a brain-penetrant ATM inhibitor and a potent radiosensitizer. This study evaluated the spectrum of radiosensitizing effects and the impact of mutation status in a panel of wild-type (WT) glioblastoma (GBM) patient-derived xenografts (PDXs).

Differential Distribution of the DNA-PKcs Inhibitor Peposertib Selectively Radiosensitizes Patient-derived Melanoma Brain Metastasis Xenografts.

Radioresistance of melanoma brain metastases limits the clinical utility of conventionally fractionated brain radiation in this disease, and strategies to improve radiation response could have significant clinical impact. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is critical for repair of radiation-induced DNA damage, and inhibitors of this kinase can have potent effects on radiation sensitivity. In this study, the radiosensitizing effects of the DNA-PKcs inhibitor peposertib were evaluated in patient-derived xenografts of melanoma brain metastases (M12, M15, M27).

Iodine Nutrition in Children ≤2 years of Age in Norway.

Background: As a component of the thyroid hormones (THs), iodine is vital for normal neurodevelopment during early life. However, both deficient and excess iodine may affect TH production, and data on iodine status in young children are scarce.

Objectives: To describe iodine nutrition (iodine status and intake) in children ≤2 y of age in Innlandet County (Norway) and to describe the associations with maternal iodine nutrition.

WSD-0922, a novel brain-penetrant inhibitor of epidermal growth factor receptor, promotes survival in glioblastoma mouse models.

Background: Although the epidermal growth factor receptor (EGFR) is a frequent oncogenic driver in glioblastoma (GBM), efforts to therapeutically target this protein have been largely unsuccessful. The present preclinical study evaluated the novel EGFR inhibitor WSD-0922.

Methods: We employed flank and orthotopic patient-derived xenograft models to characterize WSD-0922 and compare its efficacy to erlotinib, a potent EGFR inhibitor that failed to provide benefit for GBM patients.

Births in freestanding midwifery-led units in Norway: What women view as important aspects of care.

Objective: To describe what women view as important aspects of care when giving birth in freestanding midwifery-led units in Norway.

Methods: Data from four open-ended questions in the Babies Born Better survey, Version 1, 2 and 3 was used. We performed inductive content analysis to explore and describe women's experiences with the care they received.

Inadequate Iodine Intake in Mothers of Young Children in Innlandet County, Norway.

Background: Iodine has an essential role in child growth and brain development. Thus, sufficient iodine intake is particularly important in women of childbearing age and lactating women.

Objectives: This cross-sectional study aimed to describe iodine intake in a large random sample of mothers of young children (aged ≤2 y) living in Innlandet County, Norway.

Analyzing Apparent Causes of 30-Day Readmissions to Acute Care From Skilled Nursing Facilities.

This quality improvement project implemented a bidirectional apparent cause analysis of patients readmitted to 1 hospital from 8 skilled nursing facilities (SNFs). The purpose of the project was to receive input from both hospital and SNF nursing staff to critically examine the apparent causes of SNF readmissions from both settings and identify opportunities for improvement. Nurse-led measures to prevent readmissions can be found in 5 domains: improved collaboration, communication, coordination, clarification, and cause analysis.

Vitamin B status in infancy and the effect of a vitamin B injection in infants with subclinical vitamin B deficiency: study protocol for a register-based randomised controlled trial.

Introduction: Vitamin B (cobalamin) is crucial for optimal child development and growth, yet deficiency is common worldwide. The aim of this study is twofold; (1) to describe vitamin B status and the status of other micronutrients in Norwegian infants, and (2) in a randomised controlled trial (RCT), investigate the effect of vitamin B supplementation on neurodevelopment in infants with subclinical vitamin B deficiency.

Methods And Analysis: Infant blood samples, collected at public healthcare clinics, are analysed for plasma cobalamin levels.

Convection enhanced delivery of EGFR targeting antibody-drug conjugates Serclutamab talirine and Depatux-M in glioblastoma patient-derived xenografts.

Background: EGFR targeting antibody-drug conjugates (ADCs) are highly effective against EGFR-amplified tumors, but poor distribution across the blood-brain barrier (BBB) limits their efficacy in glioblastoma (GBM) when administered systemically. We studied whether convection-enhanced delivery (CED) can be used to safely infuse ADCs into orthotopic patient-derived xenograft (PDX) models of EGFRvIII mutant GBM.

Methods: The efficacy of the EGFR-targeted ADCs depatuxizumab mafodotin (Depatux-M) and Serclutamab talirine (Ser-T) was evaluated and .

Modifiable and non-modifiable risk factors for obstetric anal sphincter injury in a Norwegian Region: a case-control study.

Background: Obstetric anal sphincter injury (OASI) is a common and severe complication of vaginal delivery and may have short- and long-term consequences, including anal incontinence, sexual dysfunction and reduced quality of life. The rate of OASI varies substantially between studies and national birth statistics, and a recent meta-analysis concluded that there is a need to identify unrecognized risk factors. Our aim was therefore to explore both potential modifiable and non-modifiable risk factors for OASI.

Antenatal thyroid hormone therapy and antithyroid drug use in Norway from 2004 to 2018.

Objective: Thyroid disease during pregnancy is associated with adverse pregnancy outcomes and suboptimal fetal development. During the last decades, guidelines for diagnosing thyroid disease during pregnancy have changed considerably and there has been increased awareness. This study aimed to describe the prevalence of thyroid disease treatment over time among pregnant women in Norway.

RBBP4-p300 axis modulates expression of genes essential for cell survival and is a potential target for therapy in glioblastoma.

Background: RBBP4 activates transcription by histone acetylation, but the partner histone acetyltransferases are unknown. Thus, we investigated the hypothesis that RBBP4 interacts with p300 in a complex in glioblastoma (GBM).

Methods: shRNA silencing of RBBP4 or p300 and RNAseq was used to identify genes co-regulated by RBBP4 and p300 in GBM43 patient-derived xenograft (PDX).

Preclinical modeling in glioblastoma patient-derived xenograft (GBM PDX) xenografts to guide clinical development of lisavanbulin-a novel tumor checkpoint controller targeting microtubules.

Background: Glioblastoma (GBM) is an incurable disease with few approved therapeutic interventions. Radiation therapy (RT) and temozolomide (TMZ) remain the standards of care. The efficacy and optimal deployment schedule of the orally bioavailable small-molecule tumor checkpoint controller lisavanbulin alone, and in combination with, standards of care were assessed using a panel of IDH-wildtype GBM patient-derived xenografts.

Adequate Urinary Iodine Concentration among Infants in the Inland Area of Norway.

Considering the importance of iodine to support optimal growth and neurological development of the brain and central nervous system, this study aimed to assess and evaluate iodine status in Norwegian infants. We collected data on dietary intake of iodine, iodine knowledge in mothers, and assessed iodine concentration in mother's breast milk and in infant's urine in a cross-sectional study at two public healthcare clinics in the inland area of Norway. In the 130 mother-infant pairs, the estimated infant 24-h median iodine intake was 50 (IQR 31, 78) µg/day.

Heterogeneous delivery across the blood-brain barrier limits the efficacy of an EGFR-targeting antibody drug conjugate in glioblastoma.

Background: Antibody drug conjugates (ADCs) targeting the epidermal growth factor receptor (EGFR), such as depatuxizumab mafodotin (Depatux-M), is a promising therapeutic strategy for glioblastoma (GBM) but recent clinical trials did not demonstrate a survival benefit. Understanding the mechanisms of failure for this promising strategy is critically important.

Methods: PDX models were employed to study efficacy of systemic vs intracranial delivery of Depatux-M.

Quantitative Analysis of Tyrosine Phosphorylation from FFPE Tissues Reveals Patient-Specific Signaling Networks.

Human tissue samples commonly preserved as formalin-fixed paraffin-embedded (FFPE) tissues after diagnostic or surgical procedures in the clinic represent an invaluable source of clinical specimens for in-depth characterization of signaling networks to assess therapeutic options. Tyrosine phosphorylation (pTyr) plays a fundamental role in cellular processes and is commonly dysregulated in cancer but has not been studied to date in FFPE samples. In addition, pTyr analysis that may otherwise inform therapeutic interventions for patients has been limited by the requirement for large amounts of frozen tissue.