Targeting the low-hanging fruit of neurodegeneration.
Ontology highlight
ABSTRACT:
SUBMITTER: Mason AR
PROVIDER: S-EPMC4206158 | biostudies-literature | 2014 Oct
REPOSITORIES: biostudies-literature
Publications
Targeting the low-hanging fruit of neurodegeneration.
Mason Amanda R AR Ziemann Adam A Finkbeiner Steven S
Neurology 20141001 16
Similar Datasets
Project description:Background and Objectives: Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. The relationship between AF and iron deficiency is poorly understood. Materials and Methods: We conducted an observational study investigating the prevalence of iron deficiency in those with AF. Iron deficiency was defined by the American College of Cardiology (ACC) criteria for iron deficiency in heart failure. Results: Of 134 eligible subjects, 81 (60.4%) met the ACC definition of iron deficiency in heart failure. Those who were iron deficient were more likely to be female (OR 1.876, p = 0.005), have a history of diabetes mellitus (OR 3.085, p = 0.001) a history of stroke (OR 3.147, p = 0.016), and have higher CHA2DS2-VASc (p ≤ 0.0001) and Charlson Comorbidity Index scores (CCI) (p = 0.007). Conclusions: The prevalence of iron deficiency in those with AF appears high and warrants evaluation in a prospective study.
| S-EPMC9610053 | biostudies-literature
Project description:Significant attention has recently been given to a class of enhancers termed "super enhancers", while implying that "typical enhancers" are less important. In this report, we examine criteria for identification of super enhancers and address the need to evaluate the differences between BRD4-occupied "typical" and "super" enhancers.
| S-EPMC5834217 | biostudies-literature
Project description:Development of specific ligands for protein targets that help decode the complexities of protein-protein interaction networks is a key goal for the field of chemical biology. Despite the emergence of powerful in silico and experimental high-throughput screening strategies, the discovery of synthetic ligands that selectively modulate protein-protein interactions remains a challenge for bioorganic and medicinal chemists. This Perspective discusses emerging principles for the rational design of PPI inhibitors. Fundamentally, the approach seeks to adapt nature's protein recognition principles for the design of suitable secondary structure mimetics.
| S-EPMC3622812 | biostudies-literature
Project description:Chimeric antigen receptor T-cell (CAR-T) therapy has been prosperous in the treatment of patients with various types of relapsed/refractory (R/R) B-cell malignancies including diffuse large B-cell lymphoma (DLBCL), B-cell acute lymphoblastic leukemia (B-ALL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and multiple myeloma (MM). However, this type of therapy has faced serious hindrances in combating T-cell neoplasms. R/R T-cell malignancies are generally associated with poor clinical outcomes, and the available effective treatment approaches are very limited. CAR-T therapy of T-cell malignancies has unique impediments in comparison with that of B-cell malignancies. Fratricide, T-cell aplasia, and product contamination with malignant T cells when producing autologous CAR-Ts are the most important challenges of CAR-T therapy in T-cell malignancies necessitating in-depth investigations. Herein, we highlight the preclinical and clinical efforts made for addressing these drawbacks and also review additional potent stratagems that could improve CAR-T therapy in T-cell malignancies.
| S-EPMC8499460 | biostudies-literature
Project description:Policies that promote conversion of antibiotics from intravenous to oral route administration are considered "low hanging fruit" for hospital antimicrobial stewardship programs. We developed a simple metric based on digestive days of therapy divided by total days of therapy for targeted agents and a method for hospital comparisons. External comparisons may help identify opportunities for improving prospective implementation.
| S-EPMC10273142 | biostudies-literature
Project description:AimsTo assess whether CT-based radiomics and blood-derived biomarkers could improve the prediction of overall survival (OS) and locoregional progression-free survival (LRPFS) in patients with oropharyngeal cancer (OPC) treated with curative-intent RT.MethodsConsecutive OPC patients with primary tumors treated between 2005 and 2021 were included. Analyzed clinical variables included gender, age, smoking history, staging, subsite, HPV status, and blood parameters (baseline hemoglobin levels, neutrophils, monocytes, and platelets, and derived measurements). Radiomic features were extracted from the gross tumor volumes (GTVs) of the primary tumor using pyradiomics. Outcomes of interest were LRPFS and OS. Following feature selection, a radiomic score (RS) was calculated for each patient. Significant variables, along with age and gender, were included in multivariable analysis, and models were retained if statistically significant. The models' performance was compared by the C-index.ResultsOne hundred and five patients, predominately male (71%), were included in the analysis. The median age was 59 (IQR: 52-66) years, and stage IVA was the most represented (70%). HPV status was positive in 63 patients, negative in 7, and missing in 35 patients. The median OS follow-up was 6.3 (IQR: 5.5-7.9) years. A statistically significant association between low Hb levels and poorer LRPFS in the HPV-positive subgroup (p = 0.038) was identified. The calculation of the RS successfully stratified patients according to both OS (log-rank p < 0.0001) and LRPFS (log-rank p = 0.0002). The C-index of the clinical and radiomic model resulted in 0.82 [CI: 0.80-0.84] for OS and 0.77 [CI: 0.75-0.79] for LRPFS.ConclusionsOur results show that radiomics could provide clinically significant informative content in this scenario. The best performances were obtained by combining clinical and quantitative imaging variables, thus suggesting the potential of integrative modeling for outcome predictions in this setting of patients.
| S-EPMC10093133 | biostudies-literature
Project description:ObjectiveThere is a known association between type 2 diabetes (diabetes) and tuberculosis (TB), and TB clinics have become hubs for new diabetes diagnosis among active patients with TB. However, despite the potential to identify diabetes patients, resources limit diabetes screening opportunities to close TB contacts. We assessed the cost-effectiveness of adding opportunistic screening for diabetes during the routine TB contact investigations conducted at TB clinics.Research design and methodsWe used a Markov-based model to simulate the costs of diabetes screening, management and health outcomes, including the incidence of complications and death. All costs were considered from a health system perspective. One-way sensitivity analyses were conducted to assess the robustness of the results to various assumptions. Interventions that fall below US$50 000 per quality-adjusted life years (QALYs) are commonly considered very cost-effective, while those between $50 000 and $100 000 are considered moderately cost-effective.ResultsSimulation of diabetes screening among TB contacts resulted in not only increased survival and reduced complications but also increased costs of diabetes management. The resulting incremental cost-effectiveness ratio was $32 642 per QALY added, which is well within commonly used willingness-to-pay thresholds for cost-effectiveness. Compared with no screening, screening increased the costs by $8633 and resulted in an increase in QALYs by 0.26 per patient.ConclusionsIn the base case analysis, screening was very cost-effective given that none of the sensitivity analyses resulted in a cost-effectiveness ratio above $50 000 per QALY. Our results indicate that the expansion of diabetes screening in TB clinics is a cost-effective strategy to improve health outcomes.
| S-EPMC11816964 | biostudies-literature
Project description:BackgroundAntimicrobial stewardship programs (ASPs) are responsible for addressing unnecessary antimicrobial use. We describe our experience with a unique intervention to withdraw unnecessary antimicrobials.MethodsDesign, Setting, Participants: descriptive case series of adult inpatients at a single academic medical center, December 2021 to December 2022; Intervention: hospital-wide policy allowing ASP to discontinue inappropriate antimicrobials in select cases not resolved by prospective audit and feedback; Measures: count, date, and generic names of antimicrobials prescribed; reason for antimicrobial withdrawal (prolonged duration, no evidence of infection, or other); withdrawals by inpatient service (surgical or medical); time from antimicrobial start date to withdrawal intervention; days of therapy (DOT) saved; "nudge effect" defined as the prescribing team self-discontinuing withdrawn antimicrobial within 24 hours of withdrawal notice; appeals to withdrawals; ordering of alternative antimicrobials following withdrawal; incident infections, readmission, in-hospital mortality within 30 days of withdrawal intervention.ResultsThere were 54 antimicrobials withdrawn among 36 unique patients during the study period; piperacillin-tazobactam followed by vancomycin were the most frequently withdrawn agents; prolonged duration of therapy or prophylaxis followed by no evidence of infection were the most common reasons for withdrawal; withdrawals occurred most often on surgical services; an estimated 236 DOT (27.2 DOT per 100 patient-days) were saved; 32% of withdrawals were appealed; alternative antimicrobials were ordered following 20% of withdrawals; no incident infections, readmissions or in-hospital deaths were definitively attributed to withdrawal intervention.ConclusionsOur antimicrobial withdrawal intervention was a safe and effective addition to ASP activities to reduce inappropriate antimicrobial use and improve prescriber accountability.
| S-EPMC11019577 | biostudies-literature
Project description:Biomaterial-based tissue culture platforms have emerged as useful tools to mimic in vivo physiological microenvironments in experimental cell biology and clinical studies. We describe herein a three-dimensional (3D) tissue culture platform using a polydimethylsiloxane (PDMS)-based hanging drop array (PDMS-HDA) methodology. Multicellular spheroids can be achieved within 24 h and further boosted by incorporating collagen fibrils in PDMS-HDA. In addition, the spheroids generated from different human tumor cells exhibited distinct sensitivities toward drug chemotherapeutic agents and radiation as compared with two-dimensional (2D) cultures that often lack in vivo-like biological insights. We also demonstrated that multicellular spheroids may enable key hallmarks of tissue-based bioassays, including drug screening, tumor dissemination, cell co-culture, and tumor invasion. Taken together, these results offer new opportunities not only to achieve the active control of 3D multicellular spheroids on demand, but also to establish a rapid and cost-effective platform to study anti-cancer therapeutics and tumor microenvironments.
| S-EPMC5491519 | biostudies-literature
Project description:Mitochondrial dysfunction has achieved an increasing interest in the field of neurodegeneration as a pathological hallmark for different disorders. The impact of mitochondria is related to a variety of mechanisms and several of them can co-exist in the same disease. The central role of mitochondria in neurodegenerative disorders has stimulated studies intended to implement therapeutic protocols based on the targeting of the distinct mitochondrial processes. The review summarizes the most relevant mechanisms by which mitochondria contribute to neurodegeneration, encompassing therapeutic approaches. Moreover, a new perspective is proposed based on the heme impact on neurodegeneration. The heme metabolism plays a central role in mitochondrial functions, and several evidences indicate that alterations of the heme metabolism are associated with neurodegenerative disorders. By reporting the body of knowledge on this topic, the review intends to stimulate future studies on the role of heme metabolism in neurodegeneration, envisioning innovative strategies in the struggle against neurodegenerative diseases.
| S-EPMC6161291 | biostudies-literature