Optimizing screening practice for gestational diabetes mellitus in primary healthcare facilities in Tanzania: research protocol.

Background: Tanzania, like most low- and middle-income countries, is facing an increasing prevalence of obesity in the general population, including among women of reproductive age. Excess weight pre-pregnancy is a risk factor for the onset of gestational diabetes mellitus (GDM), which is associated with several poor pregnancy outcomes. Screening for GDM, as a primary preventive measure, is not systematically done in Tanzania.

Advances in Development of Drug Treatment for Hemophilia with Inhibitors.

Patients with hemophilia A and B who have inhibitors face limited treatment options, because replacement therapy with clotting factor VIII or IX concentrates is ineffective, particularly for patients with high-titer inhibitors. Current mainstay therapies include immune tolerance induction (through frequent injections of clotting factor VIII or IX concentrates) to eradicate inhibitors and bypassing agents (such as recombinant activated clotting factor VII and activated prothrombin complex concentrates) for the prevention and treatment of bleeding episodes. The use of these agents typically requires intravenous injections and sometimes hospitalization, which can be burdensome for patients.

Limb salvage in Christmas disease masquerading as fungating aneurysmal bone cyst.

A boy in middle childhood presented with complaints of swelling and pain in his right forearm for 4 months. He had previously undergone left above-elbow amputation due to a suspected malignant tumour in that arm. Radiological imaging revealed a locally aggressive bone tumour of the right distal radius.

Thrombin Generation Assay to Support Hematologists in the Era of New Hemophilia Therapies.

Hematology laboratories have traditionally monitored hemophilia replacement therapy by measuring coagulation factors before and after infusion. However, new drugs that do not rely on the replacement of the deficient factor require new approaches to laboratory monitoring, as factor VIII (FVIII) or factor IX (FIX) assays are no longer adequate. Non-factor therapies come in many different forms, that have one thing in common: they all increase thrombin generation.

Design and Discovery of New Dual Carbonic Anhydrase IX and VEGFR-2 Inhibitors Based on the Benzenesulfonamide-Bearing 4-Thiazolidinones/2,4-Thiazolidinediones Scaffold.

Dual-targeting drug design has become a popular approach in investigating and developing potent anticancer agents. In this regard, carbonic anhydrase (CAIX) and vascular endothelial growth factor receptor (VEGFR-2) are emerging as highly effective targets in the battle against cancer. In the present study, two series of 4-thiazolidinones/2,4-thiazolidinediones carrying 2-methylbenzenesulfonamide derivatives were designed and synthesized as potential dual CAIX/VEGFR-2 inhibitors.

Elucidation of Dysregulated Pathways Associated With Hypoxia in Oestrogen Receptor-Negative Breast Cancer.

Purpose: Carbonic anhydrase IX (CAIX) is a well-established prognostic marker in breast cancer (BC). Nevertheless, this prognostic value is yet to be confirmed in BC subtypes. This study aims to investigate the prognostic effects of CAIX in oestrogen receptor (ER)-negative (ER-) BCs and to establish pathways related to cytoplasmic CAIX expression in ER- and lymph node-negative BCs.

Comprehensive analysis of off-target and on-target effects resulting from liver-directed CRISPR-Cas9-mediated gene targeting with AAV vectors.

Comprehensive genome-wide studies are needed to assess the consequences of adeno-associated virus (AAV) vector-mediated gene editing. We evaluated CRISPR-Cas-mediated on-target and off-target effects and examined the integration of the AAV vectors employed to deliver the CRISPR-Cas components to neonatal mice livers. The guide RNA (gRNA) was specifically designed to target the factor IX gene (F9).

Acute remote ischemic conditioning enhances (CD3+)- but not (FoxP3+)-T-cell invasion in the tumor center and increases IL 17 and TNF-alpha expression in a murine melanoma model.

Introduction: Hypoxia can drive tumor progression, suppress anti-tumor immunity, and reduce the effectiveness of radiotherapy and chemotherapy. This study aimed to assess the impact of remote ischemic conditioning (RIC) on tumor oxygenation (sO2) and the anti-tumor immune response.

Material And Methods: Fourteen B16-Ova tumor-bearing C57BL/6N mice received six 5-minute RIC cycles, while another fourteen underwent anesthesia only.

Iron overload in acquired sideroblastic anemias and MDS: pathophysiology and role of chelation and luspatercept.

Besides transfusion therapy, ineffective erythropoiesis contributes to systemic iron overload in myelodysplastic syndromes with ring sideroblasts (MDS-RS) via erythroferrone-induced suppression of hepcidin synthesis in the liver, leading to increased intestinal iron absorption. The underlying pathophysiology of MDS-RS, characterized by disturbed heme synthesis and mitochondrial iron accumulation, is less well understood. Several lines of evidence indicate that the mitochondrial transporter ABCB7 is critically involved.

ORPHEE: A Real-World Study on rIX-FP Prophylaxis Use in Adolescent/Adult Patients With Hemophilia B.

Objectives: To assess the real-world efficacy and safety of recombinant factor IX albumin fusion protein (rIX-FP) in patients with hemophilia B (HB) in France.

Methods: Data on dosing frequency, weekly consumption, and bleeds before-and-after switching to rIX-FP, were collected from December 2021 to February 2024. Annualized (spontaneous) bleeding rates [A(s)BRs] were calculated only in patients on prophylaxis with a follow-up ≥ 6 months.

Restructuring of Femoral Cortical Bone During Growth and Locomotor Development of Wild Chimpanzees (Pan troglodytes verus).

Objective: Chimpanzees are altricial in terms of their locomotor development and transition from being carried to engaging in suspensory and arboreal locomotor behaviors to eventually relying on terrestrial quadrupedalism as their main form of locomotion. Here, we consider the mechanical implications of femoral cortical bone restructuring during growth and locomotor development in wild chimpanzees.

Materials And Methods: Cortical bone structure was examined in an ontogenetic sample of wild chimpanzees from a single subspecies (P.

Intracranial hemorrhage in an infant leads to the diagnosis and treatment of severe hemophilia B: a case report.

Background: Hemophilia B is a rare bleeding disorder in males, characterized by a deficiency in coagulation factor IX (FIX). Replacement of FIX with a recombinant FIX (rFIX) fusion protein, to sustain therapeutic plasma levels, is recommended as both treatment and prophylaxis to prevent bleeding episodes, particularly intracranial hemorrhage (ICH).

Case Presentation: This case report outlines the management of ICH in a 7-month-old infant with severe hemophilia B, following an accidental trauma-related event, resulting in a thin compound fracture of the left occiput.

Lipid Nanoparticle-Mediated Liver-Specific Gene Therapy for Hemophilia B.

/: Hemophilia B is a hereditary bleeding disorder due to the production of liver malfunctional factor IX (FIX). Gene therapy with viral vectors offers a cure. However, applications are limited due to pre-existing antibodies, eligibility for children under 12 years of age, hepatotoxicity, and excessive costs.

Exploration of newly synthesized deferasirox derivatives as potential anti-cancer agents via in-vitro and in-silico approaches.

Carbonic anhydrase IX (CA IX), upregulated by hypoxia-inducible factor (HIF), plays a crucial role in regulation of intracellular and extracellular pH, which is essential for the growth and spread of tumors. The overexpression of CA IX in breast cancer is linked to a low post-radiation patient survival rate. Under normoxic conditions, CA IX expression is relatively low, but hypoxia-inducible factors (HIFs) upregulate its expression when oxygen levels drop.

Exploring the Polypharmacological Potential of PCI-27483: A Selective Inhibitor of Carbonic Anhydrases IX and XII.

PCI-27483, originally developed as a potent and selective inhibitor of the serine protease Factor VIIa (FVIIa) in complex with tissue factor (TF), has demonstrated significant promise in cancer therapy. In addition to its primary mechanism of action, the presence of a sulfonamide moiety in the PCI-27483 structure suggests further activities through the inhibition of carbonic anhydrases (CAs), particularly the tumor-associated human (h)CA isoforms hCA IX and XII. This study investigates the inhibitory activity of PCI-27483 against the complete panel of active hCAs, highlighting its polypharmacological potential in cancer treatment.

Association of Fibroblast Growth Factor 23 and Cardiac Mechanics in the Cardiovascular Health Study.

Background: Elevated levels of fibroblast growth factor 23 (FGF23) are associated with left ventricular hypertrophy and heart failure (HF) in individuals with and without kidney disease. Prior studies investigated the association of FGF23 and structural cardiac changes using conventional echocardiography, which is limited in its ability to detect early cardiac dysfunction. We investigated the relationship between FGF23 levels and cardiac dynamics using two-dimensional speckle tracking echocardiography (2D-STE), a novel imaging modality.

Associations of Urine Epidermal Growth Factor With Kidney and Cardiovascular Outcomes in Individuals With CKD in SPRINT.

Introduction: Urine epidermal growth factor (uEGF) has been found to be inversely associated with kidney function loss, whereas its associations with cardiovascular disease (CVD) and mortality have not been studied.

Methods: We measured baseline uEGF levels among 2346 Systolic Blood Pressure Intervention Trial (SPRINT) participants with an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m.

TRIM28 regulates the coagulation cascade inhibited by p72 of African swine fever virus.

In 2018, African swine fever virus (ASFV) emerged in China, causing extremely serious economic losses to the domestic pig industry. Infection with ASFV can cause disseminated coagulation, leading to the consumption of platelets and coagulation factors and severe bleeding. However, the mechanism of virus-induced coagulation has yet to be established.