Economic burden of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) in Finland.

Objectives: Given that pulmonary arterial hypertension (PAH) and chronic thromboembolic hypertension (CTEPH) are rare yet severe subtypes of pulmonary hypertension significantly impacting patients' lives, this study analyzed the total societal costs of these conditions in Finland.

Methods: PAH (n = 247) and CTEPH (n = 177) patients diagnosed between 2008 and 2019 were analyzed for primary and specialty outpatient visits, emergency visits, hospitalizations, home and institutional care, sick leaves, disability pensions, and drug costs for 5 years before and after diagnosis.

Results: In PAH and CTEPH, annual specialty care number of outpatient visits increased from 3.

Cost comparison analysis of continuous versus intermittent antimicrobial therapy infusions in inpatient and outpatient care: real-world data from Finland.

Objective: This study compared the costs and nursing time associated with the delivery of continuous infusion of antibiotics via elastomeric infusion pumps (EIP) versus conventional intermittent infusion (CII) across different care pathways.

Design: Retrospective real-world data informed a cost comparison analysis that compared costs and nursing hours between infusion of antibiotics via EIP versus CII across eight care pathways in inpatient or outpatient care during infection episodes. Real-world data were obtained from patients treated within a year with parenteral antimicrobial therapy in Päijät-Häme Region, Finland.

Cystic fibrosis patient characteristics and healthcare resource utilization in Finland using linked registries.

Background: Knowledge of prevalence and epidemiology of cystic fibrosis (CF) and healthcare resource use among Finnish people with CF is incomplete.

Methods: We conducted a population-based matched cohort study using retrospective real-world data from linked Finnish national registries. Electronic healthcare data and drug purchases of 102 people with CF were analyzed between January 2015 and December 2019 (follow-up).

Effectiveness of Telemonitoring in Reducing Hospitalization and Associated Costs for Patients With Heart Failure in Finland: Nonrandomized Pre-Post Telemonitoring Study.

Background: Many patients with chronic heart failure (HF) experience a reduced health status, leading to readmission after hospitalization despite receiving conventional care. Telemonitoring approaches aim to improve the early detection of HF decompensations and prevent readmissions. However, knowledge about the impact of telemonitoring on preventing readmissions and related costs remains scarce.

The plant product quinic acid activates Ca -dependent mitochondrial function and promotes insulin secretion from pancreatic beta cells.

Background And Purpose: Quinic acid (QA) is an abundant natural compound from plant sources which may improve metabolic health. However, little attention has been paid to its effects on pancreatic beta-cell functions, which contribute to the control of metabolic health by lowering blood glucose. Strategies targeting beta-cell signal transduction are a new approach for diabetes treatment.

Isx9 Regulates Calbindin D28K Expression in Pancreatic β Cells and Promotes β Cell Survival and Function.

Pancreatic β-cell dysfunction and death contribute to the onset of diabetes, and novel strategies of β-cell function and survival under diabetogenic conditions need to be explored. We previously demonstrated that Isx9, a small molecule based on the isoxazole scaffold, drives neuroendocrine phenotypes by increasing the expression of genes required for β-cell function and improves glycemia in a model of β cell regeneration. We further investigated the role of Isx9 in β-cell survival.

Ins1(Cre) knock-in mice for beta cell-specific gene recombination.

Aims/hypothesis: Pancreatic beta cells play a central role in the control of glucose homeostasis by secreting insulin to stimulate glucose uptake by peripheral tissues. Understanding the molecular mechanisms that control beta cell function and plasticity has critical implications for the pathophysiology and therapy of major forms of diabetes. Selective gene inactivation in pancreatic beta cells, using the Cre-lox system, is a powerful approach to assess the role of particular genes in beta cells and their impact on whole body glucose homeostasis.

Neph3 associates with regulation of glomerular and neural development in zebrafish.

Neph3 (filtrin) is a membrane protein expressed in the glomerular epithelial cells (podocytes), but its role in the glomerulus is still largely unknown. To characterize the function of Neph3 in the glomerulus, we employed the zebrafish as a model system. Here we show that the expression of neph3 in pronephros starts before the onset of nephrin and podocin expression, peaks when the nephron primordium differentiates into glomerulus and tubulus, and is then downregulated upon glomerular maturation.

Trans-interaction of nephrin and Neph1/Neph3 induces cell adhesion that associates with decreased tyrosine phosphorylation of nephrin.

Slit diaphragms are specialized junctions between glomerular epithelial cells (podocytes) that are crucial for glomerular ultrafiltration. The Ig superfamily members nephrin and Neph1 are essential components of the slit diaphragm, whereas the role of Neph1 homologue Neph3 in the slit diaphragm is unknown. In the present paper we show that Neph3 homodimerizes and heterodimerizes with nephrin and Neph1.

Lipid phosphatase SHIP2 downregulates insulin signalling in podocytes.

Podocyte injury plays an important role in the development of diabetic nephropathy. Podocytes are insulin-responsive and can develop insulin resistance, but the mechanisms are unknown. To study the role of CD2-associated protein (CD2AP) in podocyte injury, we performed a yeast two-hybrid screening on a glomerular library, and found that CD2AP bound to SH2-domain-containing inositol polyphosphate 5-phosphatase 2 (SHIP2), a negative regulator of insulin signalling.

beta-Catenin mediates adriamycin-induced albuminuria and podocyte injury in adult mouse kidneys.

Background: Glomerular slit diaphragm (SD) represents a modified adherens junction composed of molecules belonging to both immunoglobulin and cadherin superfamilies. Cadherins associate with the cytosolic scaffolding protein beta-catenin, but the precise role of beta-catenin in mature or injured podocytes is not known.

Methods: The conditional podocyte-specific beta-catenin-deficient mouse line was generated using the doxycycline-inducible Cre-loxP system.

Densin and beta-catenin form a complex and co-localize in cultured podocyte cell junctions.

Densin is a member of LAP (leucine-rich repeat and PDZ domain) protein family that localizes in kidney to slit diaphragms, which are essential components of the glomerular filtration barrier. We have previously shown that densin interacts with a crucial slit diaphragm protein, nephrin. Here, we searched for novel binding partners of densin by yeast-two hybrid assay and identified beta-catenin.

Densin is a novel cell membrane protein of Sertoli cells in the testis.

Cell-cell interactions between Sertoli cells and germ cells are crucial for the maturation of germ cells in spermatogenesis but the structural and functional aspects of the interactions remain to be fully elucidated. Densin is a junction protein suggested to play a role in establishment of specific cell-cell contacts in the post-synaptic densities of the brain and the slit diaphragm of the kidney podocyte. In the present study, densin was discovered to be expressed in the testis of the man and the mouse.

Glomerular podocytes contain neuron-like functional synaptic vesicles.

Although patients with chronic renal failure are increasing worldwide, many aspects of kidney biology remain to be elucidated. Recent research has uncovered several molecular properties of the glomerular filtration barrier, in which podocytes, highly differentiated, ramified cells that enwrap the glomerular basement membrane, have been reported to be mainly responsible for filter's selectivity. We previously described that podocytes express Rab3A, a GTPase restricted to cell types that are capable of highly regulated exocytosis, such as neuronal cells.

A novel protein, densin, expressed by glomerular podocytes.

With the recent molecular findings, the podocyte is emerging as a key cell type involved in glomerular damage, but protein complexes involved remain poorly understood. To systematically search for additional podocyte molecules interacting with nephrin, a key structural molecule of the interpodocyte filtration slit, precipitation of glomerular lysates was set out with anti-nephrin antibodies to identify members of the nephrin-associated protein complex. Proteins of the precipitate were subsequently identified with MALDI-TOF mass analysis.

Patterns of nephrin and a new proteinuria-associated protein expression in human renal diseases.

Background: Many factors contribute to the pathogenesis of glomerular proteinuria, but no exact molecular mechanisms are known to date. The recently reported protein nephrin, encoded by the NPHS1 gene, appears to be crucial for the integrity of the glomerular filtration barrier.

Methods: Immunohistochemistry was used to detect possible changes in glomerular nephrin, and a new proteinuria-associated protein expression was developed in various diagnostic groups of human kidney biopsies.