Transport outcome

Understanding the mechanisms underlying resistance is critical to improving therapeutic outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). Previous work showed dynamic interconversions between epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) defines the phenotypic landscape of prostate tumors, as a potential driver of emergence of therapeutic resistance. In this study, we use in vitro and in vivo preclinical MDA PCa PDX models of resistant human prostate cancer to determine molecular mechanisms of cross-resistance between anti-androgen therapy and taxane chemotherapy, underlying the therapeutically resistant phenotype...

The use of tyrosine kinase inhibitors (TKIs) has become the mainstay of treatment in patients suffering from chronic myeloid leukemia (CML), an adult leukemia caused by a reciprocal translocation between chromosomes 9 and 22, which creates an oncogene resulting in a myeloproliferative neoplasm. These drugs function by inhibiting the ATP-binding site on the fusion oncoprotein and subsequently halting proliferative activity. The goal of this work is to investigate the current state of research into genetic factors that influence the efficacy of four FDA-approved TKIs used to treat CML...

Introduction Pre-analytical errors in cytology laboratories can significantly impact the accuracy of diagnostic results and turnaround times, ultimately affecting patient care. This article presents an evaluation of pre-analytical errors and proposes fostering strategies to enhance accuracy and efficiency in the cytology laboratory of a tertiary care hospital. The background discusses the importance of pre-analytical processes in ensuring reliable cytological diagnoses and the common errors encountered in specimen collection, handling, and transportation...

BACKGROUND: EMPA-KIDNEY assessed the effects of empagliflozin 10 mg once daily vs. placebo in 6609 patients with chronic kidney disease (CKD) at risk of progression, including 612 participants from Japan. METHODS: Eligibility required an estimated glomerular filtration rate (eGFR) of ≥ 20 < 45; or ≥ 45 < 90 ml/min/1.73m2 with a urinary albumin-to-creatinine ratio (uACR) of ≥ 200 mg/g...

Placebo-controlled trials of sodium-glucose cotransporter-2 inhibitors (SGLT2i) demonstrate kidney and cardiovascular benefits for people with type 2 diabetes (T2D) and chronic kidney disease (CKD). We used real-world data to compare the kidney and cardiovascular effectiveness of empagliflozin to dipeptidyl peptidase-4 inhibitors (DPP4i), a commonly prescribed antiglycemic medication, in a diverse population with and without CKD. Using electronic health record data from 20 large US health systems, we leveraged propensity overlap weighting to compare outcomes for empagliflozin and DPP4i initiators with T2D between 2016 and 2020...

BACKGROUND: Telemonitoring patients with cardiac implantable electronic devices (CIEDs) can improve their care management. However, the results of cost-effectiveness studies are heterogeneous. Therefore, it is still a matter of debate whether telemonitoring is worth the investment. OBJECTIVE: This systematic review aims to investigate the cost-effectiveness of telemonitoring patients with CIEDs, focusing on its key drivers, and the impact of the varying perspectives...

Storage disorders are a group of inborn errors of metabolism caused by the defective activity of lysosomal enzymes or transporters. All of these disorders have multisystem involvement with variable degrees of neurological features. Neurological manifestations are one of the most difficult aspects of treatment concerning these diseases. The available treatment modalities for some of these disorders include enzyme replacement therapy, substrate reduction therapy, hematopoietic stem cell transplantation (HSCT) and the upcoming gene therapies...

BACKGROUND: Although sodium glucose co-transporter 2 inhibitors (SGLT2is) improve heart failure (HF)-related symptoms and outcomes in HF with preserved ejection fraction (HFpEF), underlying mechanisms remain unclear. In HF with reduced EF, dapagliflozin altered ketone and fatty acid metabolites vs placebo; however, metabolite signatures of SGLT2is have not been well elucidated in HFpEF. OBJECTIVES: The goal of this study was to assess whether SGLT2i treatment altered systemic metabolic pathways and their relationship to outcomes in HFpEF...

In this study, we report the synthetic method of two distinct supramolecular metallogels, namely Mn-BDA and Cd-BDA, using Mn(II) acetate tetrahydrate, Cd(II) acetate dihydrate and butane-1,4-dicarboxylic acid (BDA). DMF, a polar aprotic solvent, was immobilized in both metallogel-networks for their synthesis. The metallogelation of Mn-BDA was successfully attained through the instant mixing of a Mn(II)-source and BDA in DMF solvent media. By applying ultrasonication, a Cd-BDA metallogel was prepared. The stoichiometry of gel-forming components concerning metal salts and the LMWG are accountable to obtain respective stable metallogels...

BACKGROUND: Exosomes assume a pivotal role as essential mediators of intercellular communication within tumor microenvironments. Within this context, long noncoding RNAs (LncRNAs) have been observed to be preferentially sorted into exosomes, thus exerting regulatory control over the initiation and progression of cancer through diverse mechanisms. RESULTS: Exosomes were successfully isolated from cholangiocarcinoma (CCA) CTCs organoid and healthy human serum. Notably, the LncRNA titin-antisense RNA1 (TTN-AS1) exhibited a conspicuous up-regulation within CCA CTCs organoid derived exosomes...

Mild traumatic brain injury (mTBI) disrupts cognitive processes that influence risk taking behavior. Little is known regarding the effects of repetitive mild injury (rmTBI) or whether these outcomes are sex specific. Risk/reward decision making is mediated by the prefrontal cortex (PFC), which is densely innervated by catecholaminergic fibers. Aberrant PFC catecholamine activity has been documented following TBI and may underlie TBI-induced risky behavior. The present study characterized the effects of rmTBI on risk/reward decision making behavior and catecholamine transmitter regulatory proteins within the PFC...

BACKGROUND: Reserpine (RES), a Vesicular Monoamine Transporter 2 (VMAT2 ) inhibitor agent, has been used in preclinical research for many years to create animal models for depression and to test experimental antidepressant strategies. Nevertheless, evidence of the potential use and validity of RES as a chronic pharmacological model for depression is lacking, and there are no comprehensive studies of the behavioral effects in conjunction with molecular outcomes. METHODS: Experiment 1...

BACKGROUND: Despite increased literature focusing on the role of the built environment (BE) in health, few cohort studies have quantitatively analyzed neighborhood walkability environment in relation to the risk of death and cardiovascular disease (CVD). This longitudinal study aimed at evaluating the association between perceived BE attributeswith mortality and major CVD based on the Prospective Urban Rural Epidemiology study in China (PURE-China). METHODS: The PURE-China study recruited 47,931 participants aged 35-70 years from 12 provinces of China between 2005 and 2009...

INTRODUCTION: Congenital syphilis (CS) has severe adverse outcomes, including abortion and death. Diagnosis of CS in asymptomatic newborns remains difficult. This study aims to evaluate an in-house polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) and blood samples (BS) to identify T. pallidum DNA in newborns. METHODOLOGY: We performed an exploratory cross-sectional study that included newborns exposed to syphilis during pregnancy (SEG) and non-exposed (SNEG) newborns, between 2019 and 2020...

Glycosylation alterations in TNBC have significant implications for tumor behavior, diagnosis, prognosis, and therapeutic strategies. Dysregulated glycosylation affects cell adhesion, signaling, immune recognition, and response to therapy in TNBC. Different types of glycosylation, including N-linked glycosylation, O-linked glycosylation, glycosphingolipid glycosylation, mucin-type glycosylation, and sialylation, play distinct roles in TNBC. The "barcoding" method based on glycosylation sites of the membrane type mannose receptor (MR) shows promise in accurately distinguishing breast cancer subtypes, including TNBC...

Virtual reality offers a multisensory experience to patients, allowing them to hear, watch, and interact in a virtual environment. Immersive virtual reality is particularly suitable for the purpose of completely isolating patients from the external environment to transport them away from the suffering related to the disease. On this state of the art, we summarize the available literature on the effectiveness of virtual reality on various physical and psychological outcomes in patients with atherosclerotic cardiovascular disease...

BACKGROUND: The likelihood of return of spontaneous circulation with conventional advanced life support is known to have an exponential decline and therefore neurological outcome after 20 min in patients with a cardiac arrest is poor. Initiation of venoarterial ExtraCorporeal Membrane Oxygenation (ECMO) during resuscitation might improve outcomes if used in time and in a selected patient category. However, previous studies have failed to significantly reduce the time from cardiac arrest to ECMO flow to less than 60 min...

Pathogenic variants in SLC6A8, the gene which encodes creatine transporter SLC6A8, prevent creatine uptake in the brain and result in a variable degree of intellectual disability, behavioral disorders (e.g., autism spectrum disorder), epilepsy, and severe speech and language delay. There are no treatments to improve neurodevelopmental outcomes for creatine transporter deficiency (CTD). In this spotlight, we summarize recent advances in innovative molecules to treat CTD, with a focus on dodecyl creatine ester, the most promising drug candidate...

Chemotherapy is a major contributor to cachexia, but studies often investigate male animals. Here, we investigated whether sex modifies the effects of chemotherapy on cachexia and BCAA metabolism. Ten-week-old CD2F1 male and female mice were treated with the chemotherapy drug cocktail folfiri (50 mg/kg 5-fluorouracil, 90 mg/kg leucovorin, and 24 mg/kg CPT11) (drug) or vehicle twice a week for 6 weeks. Insulin tolerance tests were conducted and BCAA levels and metabolism were measured in plasma and tissues...

INTRODUCTION: Improving sustainable transportation options will help cities tackle growing challenges related to population health, congestion, climate change and inequity. Interventions supporting active transportation face many practical and political hurdles. Implementation science aims to understand how interventions or policies arise, how they can be translated to new contexts or scales and who benefits. Sustainable transportation interventions are complex, and existing implementation science frameworks may not be suitable...