Brain-region-specific lipid dysregulation in L-DOPA-induced dyskinesia in a primate model of Parkinson's disease.

L-DOPA-induced dyskinesia (LID) is a significant and treatment-limiting complication in Parkinson's disease (PD) therapy, yet its mechanisms remain poorly understood. We used high-resolution mass spectrometry imaging to map brain-region-specific alterations of glycerophospholipids and sphingolipids in a female macaque model of PD with and without LID following chronic L-DOPA treatment. LID was associated with depletion of antioxidant plasmalogen phosphatidylcholines in the globus pallidus interna, claustrum, and precentral gyrus-regions critical for motor function-and elevations of polyunsaturated fatty acid-containing glycerophospholipids, indicative of increased membrane fluidity.

Machine learning framework for investigating nano- and micro-scale particle diffusion in colonic mucus.

Biosimilar artificial mucus models that mimic native mucus facilitate efficient, lab-based drug diffusion studies, addressing the costly and challenging preclinical phase of drug development, especially for nano- and micro-scale particle-based colonic drug delivery. This study presents a machine-learning-driven framework that integrates microrheological features into diffusional fingerprinting to characterize nano- and micro-scale particle diffusion patterns in mucus and assess the effect of mucus microrheology on such movements. We investigated the diffusion of fluorescent-labeled polystyrene particles in native pig mucus and two artificial mucus models.

Risk factors for further recurrences of Clostridioides difficile infection at the first and second recurrence: a retrospective cohort.

Background: Recurrent Clostridioides difficile infection is most effectively treated with faecal microbiota transplantation. Swedish and European guidelines suggest faecal microbiota transplantation after a first or second recurrence, respectively. The aims of this study were to evaluate risk factors for further relapses at the first and second recurrence, related to treatment recommendations.

The association between systemic inflammation, lung function and respiratory symptoms in the BOLD study in Northern Europe.

The role of systemic inflammation in the pathogenesis of respiratory diseases is increasingly recognized, but the relationship between individual inflammatory markers, lung function and respiratory symptoms is not well established. We studied 1,238 adults participating in the first follow-up of the Burden of Obstructive Lung Disease (BOLD) cohort study in Sweden, Norway, Iceland, and Estonia in 2019-2021. Systemic inflammation was assessed using total white blood cell (WBC) count and WBC sub-populations (neutrophils, lymphocytes, monocytes, eosinophils, basophils and neutrophil-to-lymphocyte ratio (NLR)).

Atypical Carcinoid of the Thymus: Early Diagnosis in a Case Report.

: Atypical carcinoid of the thymus is an exceptionally rare neuroendocrine tumor originating from neuroendocrine cells within the thymus. These tumors often present with no symptoms or with nonspecific clinical signs, making early diagnosis particularly challenging. Despite their rarity, atypical carcinoids are clinically significant due to their aggressive nature and relatively poor prognosis.

Free water improves sodium mobilization in furosemide treated pigs after a hyperosmotic sodium load.

Background: Hypernatremia, a common electrolyte disorder in critically ill patients, induces a hyperosmotic state linked to increased mortality and metabolic stress. While loop diuretics such as furosemide are used for fluid management, their main effect is water excretion, often worsening hypernatremia. This study aimed to determine whether free water infusion enhances sodium excretion when combined with furosemide after a sodium chloride bolus.

Discovery of tumour indicating morphological changes in benign prostate biopsies through AI.

Diagnostic needle biopsies that miss clinically significant prostate cancer (PCa) often sample benign tissue near hidden cancers. Such benign samples might still display subtle morphological signs of cancer elsewhere in the prostate. This study examined if artificial intelligence (AI) could detect these morphological clues in benign biopsies from men with elevated prostate-specific antigen (PSA) levels to predict subsequent diagnosis of clinically significant PCa within 30 months.

"Trust, Responsibility, and Making a Difference": Qualitative Insights into Why First-Line Managers in Healthcare Remain in Their Role.

Healthcare organizations face increasing challenges in retaining first-line managers, who play a key role in operational stability and patient care. Studies indicate that approximately half of all first-line managers intend to leave their position within 5 years. This highlights the need for updated knowledge about conditions under which they work.

Hb Tacoma is difficult to detect and may cause false results with different HbA1c methods.

The haemoglobin variant Hb Tacoma [HBB:c.93G > T;CD30(Arg > Ser) was detected in approximately 1 in 1000 patients tested for HbA1c at Karolinska University Hospital, Stockholm. Incidentally, five homozygous individuals were found, none of them presenting with severe haematological abnormalities.

First-Round Fecal Immunochemical Test Concentration Predicts Colorectal Cancer and Advanced Neoplasia in Second-Round Screening.

Introduction: Enhancing fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening requires identifying additional predictive factors for colorectal neoplasia beyond current-round FIT concentration. We investigated whether first-round FIT concentration could predict colorectal neoplasia detection in the second screening round, using data from the randomized controlled trial Screening of Swedish Colons (SCREESCO).

Methods: We conducted a cross-sectional analysis of SCREESCO FIT-arm participants with negative two-stool FIT (<10 μg Hb/g feces) in the first screening round, followed by a positive FIT (≥10 μg Hb/g feces) in the second round two years later with work-up colonoscopy.

Cryo-EM exposes diverse polymorphism in IAPP mutants to guide the rational design of peptide-based therapeutics.

In the pursuit of potential therapeutic agents for type 2 diabetes, non-amyloidogenic forms of the human Islet Amyloid Polypeptide (hIAPP) containing site-specific mutations are of significant interest. In the present study, we dissect the three proline mutations present in the core region of the non-amyloidogenic rat IAPP into single-point mutations at A25P, S28P, and S29P sites. We apply high-resolution cryo-electron microscopy and solve the structures of 6 polymorphs formed by these mutants, revealing the peptide's self-assembly patterns and identifying critical interactions that reinforce these structures in the presence of the β-sheet breaker.

MALNC: a new mutant NPM1/IDH2 and PML-RARA-associated lncRNA with impact on AML cell proliferation, maturation and drug response.

As the non-coding genome remains poorly characterized in acute myeloid leukemia (AML), we aimed to identify and functionally characterize novel long non-coding RNAs (lncRNAs) relevant to AML biology and treatment. We first identified lncRNAs overexpressed in AML blasts and, among them, discovered a novel transcript, which we named myeloid and AML-associated intergenic long non-coding RNA (MALNC). MALNC is overexpressed in AML, particularly in cases with the PML-RARA fusion or IDH2/NPM1 co-mutations, and is associated with a distinct gene expression profile.

Parents' experience of being present or absent during anesthesia induction of children under six months of age. A mixed randomized controlled study.

Purpose: To investigate parents' experiences of being present during anesthesia induction in young infants.

Design: A mixed randomized controlled study.

Methods: Parents of the included infants were randomized to either one parent present during induction or control (not present).

Family history of fracture and fracture risk: a meta-analysis to update the FRAX® risk assessment tool.

Unlabelled: In the largest meta-analysis of international cohorts to date, a family history of fracture is confirmed as a significant BMD-independent predictor of future fracture risk. Parental and sibling histories of fracture carry the same significance for future fracture, including the impact of family hip fracture on future hip fracture risk.

Purpose: We have undertaken a meta-analysis of international prospective cohorts to quantify the relationship between a family history of fracture and future fracture incidence.

Are Alcohol Use Disorders and Bariatric Surgery Associated? Perceptions Among Individuals Seeking Addiction Treatment.

People who undergo bariatric surgery have a higher risk of alcohol use disorder. This can be explained by a mix of biological and psychosocial factors, with various theories for this suggested. After bariatric surgery, long-term follow-up by healthcare is recommended, focusing mainly on diet.

Prediabetes transitions to normoglycaemia or type 2 diabetes and associated risk factors in the Obesity, Diabetes and Cardiovascular Disease Collaboration: an individual-level pooled analysis of 19 prospective cohort studies.

Background: With the increasing global burden of type 2 diabetes, prevention strategies that target prediabetes, a state of hyperglycaemia that puts individuals at high risk of type 2 diabetes, are required. We aimed to estimate global rates of transition from prediabetes to normoglycaemia or type 2 diabetes, stratified by age, sex, and race and ethnicity. We also aimed to quantify the effect of modifiable and non-modifiable risk factors on these transitions.

Response of greenhouse gas fluxes to simulated water level management under contrasting climate scenarios in a peatland mesocosm study.

Boreal peatlands strongly affect the global climate system by providing an important store for carbon (C) cycle and a natural source of methane. Over the past century, however, vast areas of natural peatlands have been drained to gain productive land, turning them into large potential C sources. Currently, there is a scientific debate on how to best manage historically drained boreal peatlands to improve their function in climate change mitigation.

High-affinity transferrin receptor binding improves brain delivery of bispecific antibodies at tracer dose.

Background: Transferrin receptor (TfR)-mediated transcytosis is a well-established method for delivering biologic therapeutics and diagnostics to the brain. Although moderate affinity towards TfR is beneficial for TfR-mediated brain delivery at therapeutic doses, emerging evidence has indicated that high TfR affinity may be more beneficial at tracer doses. With the development of antibody-based PET radioligands for neurodegenerative diseases, such as Alzheimer's disease, understanding the pharmacokinetics of TfR-binders at tracer dose is essential.

Voice problems in chronic cough: prevalence and implications for health and sick leave in a Northern European population.

Background: Voice problems have been reported in individuals with chronic cough, but population-based prevalence data are not yet available. While both conditions independently affect health and sick leave, their combined effects have not been studied. This study investigated the prevalence of voice problems in individuals with chronic cough and whether a cough duration of over 10 years is associated with a higher prevalence.