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Immune thrombocytopenia refractory to multiple thrombopoietin receptor agonists remains a challenging clinical problem. This commentary discusses and contextualizes the recent report on this entity from Moulis and colleagues, and how to move forward with these patients. Commentary on: Moulis et al. Difficult-to-treat primary immune thrombocytopenia in adults: Prevalence and burden. Results from the CARMEN-France Registry. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19288.

The basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factor (TF) MYC is in large part an intrinsically disordered oncoprotein. In complex with its obligate heterodimerization partner MAX, MYC preferentially binds E-Box DNA sequences (CANNTG). At promoters containing these sequence motifs, MYC controls fundamental cellular processes such as cell cycle progression, metabolism, and apoptosis. A vast network of proteins in turn regulates MYC function via intermolecular interactions. In this work, we establish another layer of MYC regulation by intramolecular interactions...

Nuclear magnetic resonance cryoporometry (NMRC) and differential scanning calorimetry thermoporometry (DSC-TPM) are powerful methods for measuring mesopore size distributions. The methods are based on the fact that, according to the Gibbs-Thomson equation, the melting point depression of a liquid confined to a pore is inversely proportional to the pore size. However, aqueous salt solutions, which inherently exist in a broad range of biological porous materials as well as technological applications such as electrolytes, do not melt at a single temperature...

PURPOSE: The purpose of this study is to assess the effect of glucocorticoid prescription feedback intervention in complex primary care institutions for regulating its inappropriate use. DESIGN SETTING AND INTERVENTIONS: A six-month cluster randomized cross-over controlled trial was conducted in primary care institutions. A total of 347 physicians from 69 participating institutions were randomly allocated to either group A or group B. Both groups were given feedback interventions or serve as control...

No abstract text is available yet for this article.

α-Thalassemia is an inherited blood disorder characterized by decreased synthesis of α-globin chains that results in an imbalance of α and β globin and thus varying degrees of ineffective erythropoiesis, decreased red blood cell (RBC) survival, chronic hemolytic anemia, and subsequent comorbidities. Clinical presentation varies depending on the genotype, ranging from a silent or mild carrier state to severe, transfusion-dependent or lethal disease. Management of patients with α-thalassemia is primarily supportive, addressing either symptoms (eg, RBC transfusions for anemia), complications of the disease, or its transfusion-dependence (eg, chelation therapy for iron overload)...

Inflammation is a temporary response of the immune system that can be treated using common anti-inflammatory drugs. However, prolonged use of these drugs increases the risk of adverse side effects. Accordingly, there is an increasing need for alternative treatments for inflammation with fewer side effects. Exosomes are extracellular vesicles secreted by most eukaryotic cells and have been studied as a candidate for cell-free therapy for inflammatory diseases due to their immunomodulatory and anti-inflammatory properties...

Labor trafficking in marijuana production remains a concealed epidemic within the expanding cannabis industry. This abstract brings attention to the systemic exploitation of vulnerable individuals engaged in cultivating, harvesting, and processing cannabis. It explores the factors contributing to labor trafficking, including demand for cheap labor, inadequate regulation, and the vulnerability of the workforce. By compiling published cases, both in peer-reviewed literature and the media, this perspective piece investigates the extent of health issues experienced by labor-trafficked victims...

BACKGROUND: In a phase 3 study of adults with active lupus nephritis, addition of voclosporin to mycophenolate mofetil (MMF) and low-dose glucocorticoids led to significant improvements in the proportion of participants achieving complete and partial renal response as well as sustained reduction in proteinuria. This analysis examined the efficacy and safety of voclosporin in a subgroup of the phase 3 study with proliferative lupus nephritis and high levels of proteinuria. METHODS: Participants were randomized to oral voclosporin (23...

OBJECTIVES: Worldwide, there is an estimated 40.3 million victims trapped in modern day slavery, including 24.9 million in forced labor and 15.4 million in forced marriage. A majority of labor and sex trafficking survivors report at least one healthcare encounter during their victimization. An approach to an informatics technology solution for identifying trafficked persons in real time, in the hospital / emergency department settings is the primary focus of this paper. MATERIALS AND METHODS: Octavia, a software application implemented in 3 California hospitals, scanned all patient encounters for social and clinical determinants that are consistent predictors of HT...

Diabetic kidney disease (DKD) is a complication of diabetes that can lead to kidney failure. Over the years, several drugs have been developed to combat this disease. In the early 90s, angiotensin blockade (ACEi and ARBs) was introduced, which revolutionized the treatment of DKD. In recent years, newer drugs such as sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, endothelin antagonists, and mineralocorticoid receptor antagonists (MRA) have shown great promise in reducing albuminuria and protecting the kidneys...

HYPOTHESIS: Enveloped viruses are pivotal in causing various illnesses, including influenza and COVID-19. The antimicrobial peptide LL-37, a critical part of the human innate immune system, exhibits potential as an antiviral agent capable of thwarting these viral threats. Its mode of action involves versatile and non-specific interactions that culminate in dismantling the viral envelope, ultimately rendering the viruses inert. However, the exact mechanism of action is not yet understood...

BACKGROUND: Oxalate nephropathy (ON) is characterized by deposition of calcium oxalate crystals in the kidney and is commonly underrecognized. Causes of ON include primary hyperoxaluria, enteric hyperoxaluria and ingestion of excess oxalate or its precursors. METHODS: We report the clinical and pathological characteristics of one of the largest series of native kidney oxalate nephropathy to date, from January 2015 to March 2023 at the Cleveland Clinic. RESULTS: We identified 60 native biopsies with oxalate deposits and excluded patients with clinically insignificant biopsies (n=12) or lack of data (n=17)...

Real-world studies of pyruvate kinase (PK) deficiency and estimates of mortality are lacking. This retrospective observational study aimed to identify patients with PK deficiency and compare their overall survival (OS) to that of a matched cohort without PK deficiency. Patients with ≥1 diagnosis code related to PK deficiency were selected from the US Veterans Health Administration (VHA) database (01/1995-07/2019); patients with a physician-documented diagnosis were included (PK deficiency cohort; index: date of first diagnosis code related to PK deficiency)...

BACKGROUND: Human trafficking is a global public health issue that is associated with serious short- and long-term morbidity. To address and prevent human trafficking, vulnerabilities to human trafficking and forces sustaining it need to be better understood among specific subpopulations. We aimed to explore risk and protective factors for human trafficking, the health impact of exploitation, and barriers and facilitators of seeking help throughout the human trafficking trajectory among forced labor and sex trafficking victims in Kampala, Uganda...

Avatrombopag is a newer thrombopoietin receptor agonist (TPO-RA) currently approved to treat chronic ITP (duration >12 months). No studies have yet evaluated the safety and effectiveness of avatrombopag in newly diagnosed ITP (duration <3 months) or persistent ITP (duration 3-12 months), and so its use in these populations is presently off-label worldwide. We hypothesize that avatrombopag has similar safety and effectiveness irrespective of ITP disease phase. To evaluate this, we performed a multicenter observational cohort study of adults with ITP treated with avatrombopag, comparing patient outcomes by disease phase (newly diagnosed/persistent versus chronic)...

The 2-Oxoglutatrate-dependent dioxygenases (2OGDs) comprise the 2-Oxoglutatrate and Fe(II)-dependent dioxygenases (2ODD) enzyme families that facilitate the biosynthesis of various compounds like gibberellin, ethylene, etc . The 2OGDs are also involved in various catabolism pathways, such as auxin and salicylic acid catabolism. Despite their important roles, 2ODDs have not been studied in potato, which is the third most important crop globally. In this study, a comprehensive genome wide analysis was done to identify all 2ODDs in potatoes, and the putative genes were analysed for the presence of the signature 2OG-FeII_Oxy (PF03171) domain and the conserved DIOX_N (PF14226) domain...

OBJECTIVES: To describe health care utilization and occupational exposures during trafficking among foreign-born people labor-trafficked in the U.S. METHODS: Retrospective analysis of immigration files for health data among 114 labor-trafficked individuals. RESULTS: Mean age was 30. Files of 38% mentioned accessing medical services at least once, mostly via hospitals (73%-81%). Forty-three percent (43%) had U.S. citizen children-indicating their children and spouses interacted with social and medical systems during exploitation...

STUDY QUESTION: Are variants of genes involved in meiosis initiation responsible for premature ovarian insufficiency (POI)? SUMMARY ANSWER: A MEIOSIN variant participates in the pathogenesis of human POI by impairing meiosis due to insufficient transcriptional activation of essential meiotic genes. WHAT IS KNOWN ALREADY: Meiosis is the key event for the establishment of the ovarian reserve, and several gene defects impairing meiotic homologous recombination have been found to contribute to the pathogenesis of POI...

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