A Dual-Pathway Responsive Mechanophore for Intelligent Luminescent Polymer Materials.

Mechanoluminescent units, when integrated into polymer matrices, undergo structural transformations in response to mechanical force, resulting in changes in fluorescence. This phenomenon holds considerable promise for the development of stress-sensing materials. Despite the high demand for robust, tunable mechanoluminescent mechanophores for force assessment and smart force-responsive materials, strategies for their design and synthesis remain underdeveloped.

Rats and mice rapidly update timed behaviors.

Keeping track of time intervals is a crucial aspect of behavior and cognition. Many theoretical models of how the brain times behavior make predictions for steady-state performance of well-learned intervals, but the rate of learning intervals in these models varies greatly, ranging from one-shot learning to learning over thousands of trials. Here, we explored how quickly rats and mice adapt to changes in interval durations using a serial fixed-interval task.

Multiplexed single-cell imaging reveals diverging subpopulations with distinct senescence phenotypes during long-term senescence induction.

Cellular senescence is a phenotypic state that contributes to the progression of age-related disease through secretion of pro-inflammatory factors known as the senescence-associated secretory phenotype (SASP). Understanding the process by which healthy cells become senescent and develop SASP factors is critical for improving the identification of senescent cells and, ultimately, understanding tissue dysfunction. Here, we reveal how the duration of cellular stress modulates the SASP in distinct subpopulations of senescent cells.

Pharmacokinetics of Nivolumab and Erythropoietin in a Rat Model of Diet-Induced Obesity.

Purpose: To investigate how obesity affects the pharmacokinetics of biologics in a rat model.

Method: Male Long-Evans rats were fed a high-fat diet from the age of 3 weeks and development of obesity was monitored by measuring body size and composition (fat and lean mass). The animals received nivolumab (1 and 8 mg/kg) or recombinant human erythropoietin (rHuEPO, 1000 IU/kg) by intravenous or subcutaneous injection.

KorB switching from DNA-sliding clamp to repressor mediates long-range gene silencing in a multi-drug resistance plasmid.

Examples of long-range gene regulation in bacteria are rare and generally thought to involve DNA looping. Here, using a combination of biophysical approaches including X-ray crystallography and single-molecule analysis for the KorB-KorA system in Escherichia coli, we show that long-range gene silencing on the plasmid RK2, a source of multi-drug resistance across diverse Gram-negative bacteria, is achieved cooperatively by a DNA-sliding clamp, KorB, and a clamp-locking protein, KorA. We show that KorB is a CTPase clamp that can entrap and slide along DNA to reach distal target promoters up to 1.

Airspace closures due to reentering space objects.

Uncontrolled reentries of space objects create a collision risk with aircraft in flight. While the probability of a strike is low, the consequences could be catastrophic. Moreover, the risk is rising due to increases in both reentries and flights.

YAT2150 is irresistible in Plasmodium falciparum and active against Plasmodium vivax and Leishmania clinical isolates.

We recently characterized the potent antiplasmodial activity of the aggregated protein dye YAT2150, whose presumed mode of action is the inhibition of protein aggregation in the malaria parasite. Using single-dose and ramping methods, assays were done to select Plasmodium falciparum parasites resistant to YAT2150 concentrations ranging from 3× to 0.25× the in vitro IC of the compound (in the two-digit nM range) and performed a cross-resistance assessment in P.

Identification of candidate genes involved in Zika virus-induced reversible paralysis of mice.

Zika virus (ZIKV) causes a variety of peripheral and central nervous system complications leading to neurological symptoms such as limb weakness. We used a mouse model to identify candidate genes potentially involved in causation or recovery from ZIKV-induced acute flaccid paralysis. Using Zikv and Chat chromogenic and fluorescence in situ RNA hybridization, electron microscopy, immunohistochemistry, and ZIKV RT-qPCR, we determined that some paralyzed mice had infected motor neurons, but motor neurons are not reduced in number and the infection was not present in all paralyzed mice; hence infection of motor neurons were not strongly correlated with paralysis.

Altered olfactory responses in Fmr1 KO mice.

Fragile X syndrome (FXS) is a neurodevelopmental disorder oftentimes associated with abnormal social behaviors and altered sensory responsiveness. It is hypothesized that the inappropriate filtering of sensory stimuli, including olfaction, can lead to aberrant social behavior in FXS. However, previous studies investigating olfaction in animal models of FXS have shown inconsistent results.

Characterizing safety, toxicity, and breast cancer risk reduction using a long-term fulvestrant eluting implant.

For individuals at high risk of developing breast cancer, interventions to mitigate this risk include surgical removal of their breasts and ovaries or five years treatment with the anti-estrogen tamoxifen or aromatase inhibitors. We hypothesized that a silicone based anti-estrogen-eluting implant placed within the breast would provide the risk reduction benefit of hormonal therapy, but without the adverse effects that limit compliance. To this end, we demonstrate that when placed adjacent to mammary tissue in the 7,12-dimethylbenz[a]anthracene-induced rat breast cancer model a fulvestrant-eluting implant delays breast cancer with minimal systemic exposure.

Improving Mental Health and Well-Being Through the Paradym App: Quantitative Study of Real-World Data.

Background: With growing evidence suggesting that levels of emotional well-being have been decreasing globally over the past few years, demand for easily accessible, convenient, and affordable well-being and mental health support has increased. Although mental health apps designed to tackle this demand by targeting diagnosed conditions have been shown to be beneficial, less research has focused on apps aiming to improve emotional well-being. There is also a dearth of research on well-being apps structured around users' lived experiences and emotional patterns and a lack of integration of real-world evidence of app usage.

Per- and Polyfluoroalkyl Substances (PFAS) Exposure in the U.S. Population: NHANES 1999-March 2020.

Per- and polyfluoroalkyl substances (PFAS), also known as "forever chemicals" because of their persistence in the environment, have been used in many commercial applications since the 1940s. Of late, the detection of PFAS in drinking water throughout the United States has raised public and scientific concerns. To understand PFAS exposure trends in the general U.

Skeletal muscle disorders as risk factors for type 2 diabetes.

The incidence and prevalence of muscular disorders and of type 2 diabetes (T2D) is increasing and both represent highly significant healthcare problems, both economically and compromising quality of life. Interestingly, skeletal muscle dysfunction and T2D share some commonalities including dysregulated glucose homeostasis, increased oxidative stress, dyslipidemia, and cytokine alterations. Several lines of evidence have hinted to a relationship between skeletal muscle dysfunction and T2D.

Development of a health equity tool in resuscitation sciences and application to current research in extracorporeal cardiopulmonary resuscitation for cardiac arrest.

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used for adults with cardiac arrest (CA) refractory to Advanced Cardiovascular Life Support (ACLS). Concerns exist that adding ECPR could worsen health inequities, defined as differences in health outcomes that are unfair or unjust. Current guidelines do not explicitly address this issue.

Cost-effectiveness Analysis of Uterus Transplantation versus Gestational Carrier for Treatment of Absolute Uterine Factor Infertility.

Importance: Patients with uterine factor infertility (UFI) have few options for family building. Uterus transplant is a feasible treatment for some patients; however, cost remains a significant concern.

Objective: To compare the cost effectiveness of treatment for patients with absolute uterine factor infertility to achieve 1-2 singleton births by gestational carrier or uterus transplant DESIGN: Decision analysis from the United States healthcare sector perspective, with time horizons to achieve one or two singleton births.

Preconception GLP-1 Receptor Agonist Use Associated with Decreased Risk for Adverse Obstetric Outcomes.

Background: The use of glucagon-like-peptide-1 receptor agonists (GLP-1RAs) has greatly increased in patients of reproductive age within the past four years. However, there is minimal research into the long-term impact of these medications on future pregnancies.

Objectives: We aimed to evaluate the association between adverse obstetric outcomes and antecedent GLP-1RA use using a nationally representative database.

A new Mediterranean Lifestyle Pyramid for children and youth: a critical lifestyle tool for preventing obesity and associated cardiometabolic diseases in a sustainable context.

Cardiovascular risk factors begin in childhood and track into adulthood, increasing the possibility of impaired cardiometabolic health. Adopting healthy dietary patterns can help curb childhood obesity, a worrisome epidemic problem at present. In the era of personalized nutrition, dietary recommendations should be adapted to different stages of life, including children (older than 3 years) and adolescents.

Survival Among Patients Treated with Total Mesorectal Excision or Selective Watch-and-Wait After Total Neoadjuvant Therapy: A Pooled Analysis of the CAO/ARO/AIO-12 and OPRA Randomized Phase II Trials.

Background: Prospective data comparing watch-and-wait (WW) to mandatory total mesorectal excision (TME) in patients with locally advanced rectal cancer (LARC) remains limited, as randomized control trials assessing these two treatment approaches are considered impractical. This pooled analysis of the CAO/ARO/AIO-12 and OPRA trials analyzes survival outcomes among LARC patients managed with either a selective WW or mandatory TME strategy following total neoadjuvant therapy (TNT).

Patients And Methods: The CAO/ARO/AIO-12 and OPRA trials were multicenter, phase II trials that randomized patients with stage II/III rectal cancer to receive either induction or consolidation chemotherapy as part of TNT.

Therapeutic novelties in acute heart failure and practical perspectives.

Acute Heart Failure (AHF) is a leading cause of death and represents the most frequent cause of unplanned hospital admission in patients older than 65 years. Since the past decade, several randomized clinical trials have highlighted the importance and pivotal role of certain therapeutics, including decongestion by the combination of loop diuretics, the need for rapid goal-directed medical therapies implementation before discharge, risk stratification, and early follow-up after discharge therapies. Cardiogenic shock, defined as sustained hypotension with tissue hypoperfusion due to low cardiac output and congestion, is the most severe form of AHF and mainly occurs after acute myocardial infarction, which can progress to multiple organ failure.

Robotic versus manual disinfection of global priority pathogens at COVID-19 dedicated hospitals.

Background: Twelve bacterial families were identified as global priority pathogens by the World Health Organization in 2017, recognizing the greatest threat they pose to human health and the declining antibiotic efficacy. Robotics has emerged as a swift and contactless tool for disinfecting bacterial surface contamination in healthcare facilities, however, head-to-head comparison of disinfection efficacy of robotic versus manual disinfections is limited. This study aimed at comparing how robotic disinfection performs over manual disinfection against the global priority pathogens in the healthcare setting.

Online analysis of Amazon's soils through reflectance spectroscopy and cloud computing can support policies and the sustainable development.

Analyzing soil in large and remote areas such as the Amazon River Basin (ARB) is unviable when it is entirely performed by wet labs using traditional methods due to the scarcity of labs and the significant workforce requirements, increasing costs, time, and waste. Remote sensing, combined with cloud computing, enhances soil analysis by modeling soil from spectral data and overcoming the limitations of traditional methods. We verified the potential of soil spectroscopy in conjunction with cloud-based computing to predict soil organic carbon (SOC) and particle size (sand, silt, and clay) content from the Amazon region.

Functional movement disorders in dopa-responsive dystonia.

Background: Functional neurological movement disorders are common and disabling. Little is known about their coexistence with other non-functional movement disorders and their impact on the general disease burden.

Objectives: Investigating frequency and characteristics of functional movement disorders in GCH1-positive dopa-responsive dystonia patients.

The bidirectional relationship between pain and tobacco use: Insights from the longitudinal Population Assessment of Tobacco and Health (PATH) study.

Background: Tobacco smoking remains the leading preventable cause of death, whereas chronic pain is the leading cause of disability. Chronic pain and tobacco smoking are closely interrelated. We investigated whether pain predicts daily cigarette smoking and if daily cigarette smoking predicts the development of pain.