Telomerase reverse transcriptase gene knock-in unleashes enhanced longevity and accelerated damage repair in mice.

While previous research has demonstrated the therapeutic efficacy of telomerase reverse transcriptase (TERT) overexpression using adeno-associated virus and cytomegalovirus vectors to combat aging, the broader implications of TERT germline gene editing on the mammalian genome, proteomic composition, phenotypes, lifespan extension, and damage repair remain largely unexplored. In this study, we elucidate the functional properties of transgenic mice carrying the Tert transgene, guided by precise gene targeting into the Rosa26 locus via embryonic stem (ES) cells under the control of the elongation factor 1α (EF1α) promoter. The Tert knock-in (TertKI) mice harboring the EF1α-Tert gene displayed elevated telomerase activity, elongated telomeres, and extended lifespan, with no spontaneous genotoxicity or carcinogenicity.

Sudden Cardiac Death Reporting in US Patients on Dialysis: Comparison of United States Renal Data System and National Death Index Data.

Key Points: For patients with ESKD treated with hemodialysis, the causes of death reported by the United States Renal Data System and the National Death Index show substantial disagreement. In particular, the proportion of sudden cardiac death was almost two-fold higher in the United States Renal Data System (42%) compared with the National Death Index (22%).

Background: Cause-specific mortality data from the United States Renal Data System (USRDS) form the basis for identifying cardiovascular disease (CVD), specifically sudden cardiac death (SCD), as the leading cause of death for patients on dialysis.

BATF is a major driver of NK cell epigenetic reprogramming and dysfunction in AML.

Myelodysplastic syndrome and acute myeloid leukemia (AML) belong to a continuous disease spectrum of myeloid malignancies with poor prognosis in the relapsed/refractory setting necessitating novel therapies. Natural killer (NK) cells from patients with myeloid malignancies display global dysfunction with impaired killing capacity, altered metabolism, and an exhausted phenotype at the single-cell transcriptomic and proteomic levels. In this study, we identified that this dysfunction was mediated through a cross-talk between NK cells and myeloid blasts necessitating cell-cell contact.

hyve, a compositional visualisation engine for brain imaging data.

Visualisations facilitate the interpretation of geometrically structured data and results. However, heterogeneous geometries-such as volumes, surfaces, and networks-have traditionally mandated different software approaches. We introduce hyve, a Python library that uses a compositional functional framework to enable parametric implementation of custom visualisations for different brain geometries.

Reprogramming Megakaryocytes for Controlled Release of Platelet-like Particles Carrying a Single-Chain Thromboxane A Receptor-G-Protein Complex with Therapeutic Potential.

In this study, we reported that novel single-chain fusion proteins linking thromboxane A (TXA) receptor (TP) to a selected G-protein α-subunit q (SC-TP-Gαq) or to α-subunit s (SC-TP-Gαs) could be stably expressed in megakaryocytes (MKs). We tested the MK-released platelet-linked particles (PLPs) to be used as a vehicle to deliver the overexpressed SC-TP-Gαq or the SC-TP-Gαs to regulate human platelet function. To understand how the single-chain TP-Gα fusion proteins could regulate opposite platelet activities by an identical ligand TXA, we tested their dual functions-binding to ligands and directly linking to different signaling pathways within a single polypeptide chain-using a 3D structural model.

Quality of systematic reviews on timing of complementary feeding for early childhood allergy prevention.

Background: Only rigorously prepared analyses can provide the highest level of evidence to inform decision-making. Several recent systematic reviews (SRs) examined the hypothesis that the early introduction of specific allergenic complementary foods (CFs) to infants may lead to a lower incidence of one or more allergic outcomes. However, the methodological rigour and quality of reporting of SRs in this area has not yet been systematically evaluated.

Decision value signals in the ventromedial prefrontal cortex and motivational and hedonic symptoms across mood and psychotic disorders.

Deficits in motivation and pleasure are common across many psychiatric disorders, and manifest as symptoms of amotivation and anhedonia, which are prominent features of both mood and psychotic disorders. Here we provide evidence for an association between neural value signals and symptoms of amotivation and anhedonia across adults with major depression, bipolar disorder, schizophrenia, or no psychiatric diagnosis. We found that value signals in the ventromedial prefrontal cortex (vmPFC) during intertemporal decision-making were dampened in individuals with greater motivational and hedonic deficits, after accounting for primary diagnosis.

Neferine, a novel ROCK1-targeting inhibitor, blocks EMT process and induces apoptosis in non-small cell lung cancer.

The compounds derived from Traditional Chinese Medicines have shown various pharmacological activities with unique advantages, especially in the aspect of antitumor. Neferine (Nef), a natural compound, extracted from green seed embryos of Lotus (Nelumbo nucifera Gaertn.) also exerts antitumor effects on cancers.

Structural imaging studies of patients with chronic pain: an anatomical likelihood estimate meta-analysis.

Neuroimaging is a powerful tool to investigate potential associations between chronic pain and brain structure. However, the proliferation of studies across diverse chronic pain syndromes and heterogeneous results challenges data integration and interpretation. We conducted a preregistered anatomical likelihood estimate meta-analysis on structural magnetic imaging studies comparing patients with chronic pain and healthy controls.

Risk of Thrombosis in Adult Philadelphia-Positive ALL Treated with an Asparaginase-Free ALL Regimen.

Background: venous thromboembolism (VTE) is a well-known complication in adults with acute lymphoblastic leukemia (ALL), especially in patients treated with asparaginase (ASNase)-including regiments. However, VTE risk in adult Philadelphia-positive ALL (Ph+ve ALL) patients treated with non-hyperCVAD chemotherapy is unclear. In this study, we examined VTE incidence in adult Ph+ve ALL patients treated with imatinib plus a pediatric-inspired asparaginase (ASNase)-free regimen modified from the Dana Farber Cancer Institute (DFCI) ALL protocol.

Brain Responses to Noxious Stimuli in Patients With Chronic Pain: A Systematic Review and Meta-analysis.

Importance: Functional neuroimaging is a valuable tool for understanding how patients with chronic pain respond to painful stimuli. However, past studies have reported heterogenous results, highlighting opportunities for a quantitative meta-analysis to integrate existing data and delineate consistent associations across studies.

Objective: To identify differential brain responses to noxious stimuli in patients with chronic pain using functional magnetic resonance imaging (fMRI) while adhering to current best practices for neuroimaging meta-analyses.

Distinct Insular Functional Connectivity Changes Related to Mood and Fatigue Improvements in Major Depressive Disorder Following Tai Chi Training: A Pilot Study.

: Tai chi (TC), a contemplative practice combining slow movements and deep breathing, has been shown to be clinically effective in alleviating depressive symptoms. Feelings of fatigue or low vitality often accompany major depressive disorder (MDD) though they are commonly overlooked and not well understood neurologically. By using resting state functional connectivity (rs-FC) using the insula as the seed, this study examines the relationship between mood and vitality symptoms in MDD and how they are impacted by TC training.

Convergent neural representations of experimentally-induced acute pain in healthy volunteers: A large-scale fMRI meta-analysis.

Characterizing a reliable, pain-related neural signature is critical for translational applications. Many prior fMRI studies have examined acute nociceptive pain-related brain activation in healthy participants. However, synthesizing these data to identify convergent patterns of activation can be challenging due to the heterogeneity of experimental designs and samples.

Universal venous thromboembolism policy is effective but may not adequately protect hospitalized cancer patients with larger BMI.

Routine VTE prophylaxis is recommended for hospitalized patients, but its effectiveness and safety in cancer patients is unclear. By observation, larger patients seemed poorly covered by the prophylaxis policy. The effectiveness and safety of VTE prophylaxis policy in the hospitalized patients, their potential risk factors such as BMI were examined.

Epidemiology of chronic pain in Ukraine: Findings from the World Mental Health Survey.

Chronic pain can pose a serious challenge in everyday life for many individuals globally, especially in developing countries, but studies explicitly exploring risk factors of chronic pain beyond demographic characteristics using survey data have been scarce. To address this problem, this study analyzed World Health Organization data on chronic pain in Ukraine to explore demographic, psychological, and treatment perception-related risk factors to chronic pain. We replicated previous reports of older age, female sex, married status, inadequate financial resources, and comorbidity of other physical conditions as significant demographic risk factors for chronic pain diagnosis but not necessarily for severe pain.

Cinnamaldehyde Improves Lifespan and Healthspan in Models for Alzheimer's Disease.

Cinnamon extract has been reported to have positive effects in fruit fly and mouse models for Alzheimer's disease (AD). However, cinnamon contains numerous potential active compounds that have not been individually evaluated. The main objective of this study was to evaluate the impact of cinnamaldehyde, a known putative active compound in cinnamon, on the lifespan and healthspan of models for Alzheimer's disease, which overexpress A and MAPT (Tau).

Chemical Stability of Plerixafor after Opening of Single-Use Vial.

Background: The addition of the immunostimulant plerixafor to the current standard-of-care regimens of granulocyte colony-stimulating growth factor with or without chemotherapy has improved clinical results in terms of successful stem cell mobilization and the outcomes of stem cell transplant in various settings. With this medical innovation has come an added financial cost for institutions where stem cell transplants are routinely performed, and there may be a further financial burden when the contents of partial vials of the drug are wasted, given that plerixafor vials (Mozobil, Sanofi-Aventis Canada Inc) are currently deemed suitable only for single use.

Objective: To determine whether the portion of plerixafor remaining in an opened vial of the Mozobil product after administration of a single dose is chemically stable, by comparison with the original product.

Anaphylaxis-related deaths in Ontario: a retrospective review of cases from 1986 to 2011.

Background: Examining deaths caused by anaphylaxis may help identify factors that may decrease the risk of these unfortunate events. However, information on fatal anaphylaxis is limited. The objectives of our study were to examine all cases of fatal anaphylaxis in Ontario to determine cause of death, associated features, co factors and trends in mortality.

Persuasive attributes of medication adherence interventions for older adults: a systematic review.

Background: Low adherence to prescribed medications leads to serious negative health consequences in older adults. Effective interventions that improve adherence are often labor-intensive and complex. However, most studies do not analyze the separate effects of the components.

Providing clinicians with a patient's 10-year cardiovascular risk improves their statin prescribing: a true experiment using clinical vignettes.

Background: Statins are effective for primary prevention of cardiovascular (CV) disease, the leading cause of death in the world. Multinational guidelines emphasize CV risk as an important factor for optimal statin prescribing. However, it's not clear how primary care providers (PCPs) use this information.

Respiratory syncytial virus induces insensitivity to beta-adrenergic agonists in mouse lung epithelium in vivo.

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants and children worldwide. We wished to determine whether intratracheal administration of beta-agonists improved alveolar fluid clearance (AFC) across the distal respiratory epithelium of RSV-infected mice. Following intranasal infection with RSV strain A2, AFC was measured in anesthetized, ventilated BALB/c mice by instillation of 5% BSA into the dependent lung.

Adenosine regulation of alveolar fluid clearance.

Adenosine is a purine nucleoside that regulates cell function through G protein-coupled receptors that activate or inhibit adenylyl cyclase. Based on the understanding that cAMP regulates alveolar epithelial active Na(+) transport, we hypothesized that adenosine and its receptors have the potential to regulate alveolar ion transport and airspace fluid content. Herein, we report that type 1 (A(1)R), 2a (A(2a)R), 2b (A(2b)R), and 3 (A(3)R) adenosine receptors are present in rat and mouse lungs and alveolar type 1 and 2 epithelial cells (AT1 and AT2).