Acton

Glioblastoma (GBM) remains an incurable disease with an extremely high five-year recurrence rate. We studied apoptosis in glioma stem cells (GSCs) in response to HDAC inhibition (HDACi) combined with MEK1/2 inhibition (MEKi) or BCL-2 family inhibitors. MEKi effectively combined with HDACi to suppress growth, induce cell cycle defects, and apoptosis, as well as to rescue the expression of the pro-apoptotic BH3-only proteins BIM and BMF. A RNAseq analysis of GSCs revealed that HDACi repressed the pro-survival BCL-2 family genes MCL1 and BCL-XL...

Triple-negative breast cancer (TNBC) is an aggressive cancer that lacks specific molecular targets that are often used for therapy. The refractory rate of TNBC to broad-spectrum chemotherapy remains high; however, the combination of newly developed treatments with the current standard of care has delivered promising anti-tumor effects. One mechanism employed by TNBC to avoid cell death is the increased expression of the anti-apoptotic protein, myeloid cell leukemia 1 (MCL1). Multiple studies have demonstrated that increased MCL1 expression enables resistance to platinum-based chemotherapy...

Blood steroid profile is a recently introduced test in India that is commercially available through a few diagnostic laboratories. In adult women, ACTH-stimulated steroid panel helps to differentiate polycystic ovary syndrome (PCOS) from nonclassical forms of CAH. However, the interpretation of ACTH-stimulated steroid panels is often impeded by the limited availability of reference ranges. Here, we report the adrenal steroid levels after stimulation with Acton Prolongatum in Asian Indian women of reproductive age...

INTRODUCTION: Studies have shown some benefits to single approaches to psychological therapies for the treatment of anxiety in people with intellectual disability such as modified cognitive-behavioural therapy and mindfulness. To our knowledge, no studies have used a multicomponent approach for the individual treatment of anxiety-related disorders in this population group. A co-production group of clinical experts and people with intellectual disability has created a novel multicomponent anxiety management programme (MCAMP-ID)...

Standard automated perimetry, a psychophysical task performed routinely in eyecare clinics, requires observers to maintain fixation for several minutes at a time in order to measure visual field sensitivity. Detection of visual field damage is confounded by eye movements, making the technique unreliable in poorly attentive individuals and those with pathologically unstable fixation, such as nystagmus. Microperimetry, which utilizes 'partial gaze-contingency' (PGC), aims to counteract eye movements but only corrects for gaze position errors prior to each stimulus onset...

INTRODUCTION: Persistent symptoms after COVID-19 infection ("long COVID") negatively affects almost half of COVID-19 survivors. Despite its prevalence, its pathophysiology is poorly understood, with multiple host systems likely affected. Here, we followed patients from hospital to discharge and used a systems-biology approach to identify mechanisms of long COVID. METHODS: RNA-seq was performed on whole blood collected early in hospital and 4-12 weeks after discharge from 24 adult COVID-19 patients (10 reported post-COVID symptoms after discharge)...

Background: Postpartum contraceptive use can help prevent short-interval pregnancies, which have been associated with adverse neonatal and maternal health outcomes. Many contraceptive methods are safe for postpartum use, but patients and providers may be confused as to what impact hormonal contraception has on lactation. We performed a scoping review of the most recent U.S.-based guidelines regarding hormonal contraception on lactation to provide synthesis and recommendations to aid providers in counseling their patients...

Power is an all-pervasive, and fundamental force in human relationships and plays a valuable role in social, political, and economic interactions. Power differences are important in social groups in enhancing group functioning. Most people want to have power and there are many benefits to having power. However, power is a corrupting force and this has been a topic of interest for centuries to scholars from Plato to Lord Acton. Even with increased knowledge of power's corrupting effect and safeguards put in place to counteract such tendencies, power abuse remains rampant in society suggesting that the full extent of this effect is not well understood...

The COVID-19 pandemic has created an urgency to study the host gene response that leads to variable clinical presentations of the disease, particularly the critical illness response. miRNAs have been implicated in the mechanism of host immune dysregulation and thus hold potential as biomarkers and/or therapeutic agents with clinical application. Hence, further analyses of their altered expression in COVID-19 is warranted. An important basis for this is identifying appropriate reference genes for high quality expression analysis studies...

INTRODUCTION:  Accurate medical documentation is important in the perioperative period, ensuring the safe transfer of information between teams involved in the surgical patient's care. This has been highlighted by multiple standards of care guidelines within the United Kingdom. The use of standardized pre-templated documents has displayed significant success in minimizing errors during the admission and operative stages. The aim of this study is to evaluate whether a similar proforma for the post-operative stage is successful in orthopedic patients...

OBJECTIVES: Ocular pain is a commonly reported finding in the intravitreal injection procedure, but post-injection experiences and patient adherence to treatment remain underexplored. We therefore aimed to identify key variations in the intravitreal injection procedure that may influence pain, and to gain insights into the post-injection experience and treatment adherence from the perspective of patients and practitioners. DESIGN: Qualitative semistructured interview study using reflexive thematic analysis of transcripts...

OBJECTIVES: The aim of this study was to explore risk factors for developing hospital-acquired pressure injuries (HAPIs) among critically ill adult inpatients. BACKGROUND: Hospital-acquired pressure injuries remain a priority quality focus for Magnet® organizations. Recent studies cite medical devices as a primary cause, yet published risk assessments lack inclusion of those threats. METHODS: Nurses at a 434-bed, 4-time Magnet®-designated hospital led a retrospective study acros 9 American Nurses Credentialing Center-designated facilities...

Chemotherapy-induced peripheral neuropathy (CIPN) is a major unmet medical need with limited treatment options. Despite different mechanisms of action, diverse chemotherapeutics can cause CIPN through a converged pathway─an active axon degeneration program that engages the dual leucine zipper kinase (DLK). DLK is a neuronally enriched kinase upstream in the MAPK-JNK cascade, and while it is dormant under physiological conditions, DLK mediates a core mechanism for neuronal injury response under stress conditions, making it an attractive target for treatment of neuronal injury and neurodegenerative diseases...

Delhi, India, suffers from periods of very poor air quality, but little is known about the chemical production of secondary pollutants in this highly polluted environment. During the postmonsoon period in 2018, extremely high nighttime concentrations of NOx (NO and NO2 ) and volatile organic compounds (VOCs) were observed, with median NOx mixing ratios of ∼200 ppbV (maximum of ∼700 ppbV). A detailed chemical box model constrained to a comprehensive suite of speciated VOC and NOx measurements revealed very low nighttime concentrations of oxidants, NO3 , O3 , and OH, driven by high nighttime NO concentrations...

Our aim was to document the effects of genotype HFE p.C282Y/p.C282Y and hemochromatosis-associated laboratory and clinical manifestations on platelet counts (PC). We compiled genotype (p.C282Y/p.C282Y or HFE wt/wt (absence of p.C282Y and p.H63D (rs1799945)), age, sex, body mass index, presence/absence of chronic fatigue, swelling/tenderness of second/third metacarpophalangeal joints, and hyperpigmentation, transferrin saturation (TS), serum ferritin (SF), hemoglobin levels, absolute neutrophil, lymphocyte, and monocyte counts, C-reactive protein levels, and PC of non-Hispanic white participants in a hemochromatosis and iron overload post-screening clinical examination...

BACKGROUND: Introduction of novel therapies for cystic fibrosis (CF) raises the question of whether traditional treatments can be withdrawn. Nebulized hypertonic saline (HS) potentially could be discontinued in patients receiving dornase alfa (DA). RESEARCH QUESTION: In the era before modulators, did people with CF who are F508del homozygous (CFF508del ) and who received DA and HS have better preserved lung function than those treated with DA only? STUDY DESIGN AND METHODS: Retrospective analysis of the Cystic Fibrosis Foundation Patient Registry data (2006-2014)...

3CLpro protease from SARS-CoV-2 is a primary target for COVID-19 antiviral drug development. Here, we present a protocol for 3CLpro production in Escherichia coli. We describe steps to purify 3CLpro , expressed as a fusion with the Saccharomyces cerevisiae SUMO protein, with yields up to 120 mg L-1 following cleavage. The protocol also provides isotope-enriched samples suitable for nuclear magnetic resonance (NMR) studies. We also present methods to characterize 3CLpro by mass spectrometry, X-ray crystallography, heteronuclear NMR, and a Förster-resonance-energy-transfer-based enzyme assay...

Upon initial immune challenge, dendritic cells (DCs) migrate to lymph nodes and interact with fibroblastic reticular cells (FRCs) via C-type lectin-like receptor 2 (CLEC-2). CLEC-2 binds to the membrane glycoprotein podoplanin (PDPN) on FRCs, inhibiting actomyosin contractility through the FRC network and permitting lymph node expansion. The hyaluronic acid receptor CD44 is known to be required for FRCs to respond to DCs but the mechanism of action is not fully elucidated. Here, we use DNA-PAINT, a quantitative single molecule super-resolution technique, to visualize and quantify how PDPN clustering is regulated in the plasma membrane of FRCs...

BACKGROUND: Nutrition facts tables (NFTs) on pre-packaged foods are widely used but poorly understood by consumers. Several countries have implemented front-of-package labels (FOPLs) that provide simpler, easier to use nutrition information. In October 2020, Mexico revised its FOPL regulations to replace industry-based Guideline Daily Amount (GDA) FOPLs with 'Warning' FOPLs, which display stop signs on foods high in nutrients of concern, such as sugar and sodium. This study examined self-reported awareness, use, and understanding of NFTs and FOPLs among young people in six countries with different FOPLs, with an additional focus on changes before and after implementation of Mexico's FOPL warning policy...

The maturation of RNA from its nascent transcription to ultimate utilization (e.g., translation, miR-mediated RNA silencing, etc.) involves an intricately coordinated series of biochemical reactions regulated by RNA binding proteins (RBPs). Over the past several decades, there has been extensive effort to elucidate the biological factors that control the specificity and selectivity of RNA target binding and downstream function. Polypyrimidine tract binding protein 1 (PTBP1) is an RBP that is involved in all steps of RNA maturation and serves as a key regulator of alternative splicing, and therefore understanding its regulation is of critical biologic importance...