The Effect of Carnosine Supplementation on Musculoskeletal Health in Adults with Prediabetes and Type 2 Diabetes: A Secondary Analysis of a Randomized Controlled Trial.

Background/objectives: Type 2 diabetes (T2D) is associated with an increased risk of adverse musculoskeletal outcomes likely due to heightened chronic inflammation, oxidative stress, and advanced glycation end-products (AGE). Carnosine has been shown to have anti-inflammatory, anti-oxidative, and anti-AGE properties. However, no clinical trials have examined the impact of carnosine on musculoskeletal health in adults with prediabetes or T2D.

A numerical investigation of the effects of model parameterization on the delineation of source protection zones under uncertainty.

Source protection zone delineation has evolved over the past decades from fixed radius or analytical and numerical methods which do not consider uncertainty, to more complex stochastic numerical approaches. In this paper we explore options for delineating a source protection zone, while considering the inherent uncertainty involved in characterizing hydraulic conductivity. We consider a representative pumping well in an unconfined alluvial aquifer under steady-state flow conditions, with the hydraulic conductivity distribution inferred from borehole lithology data in the West Melton area near Christchurch, New Zealand.

An expert consensus statement on biomarkers of ageing for use in intervention studies.

Biomarkers of ageing serve as important outcome measures in longevity-promoting interventions. However, there is limited consensus on which specific biomarkers are most appropriate for human intervention studies. This work aimed to address this need by establishing an expert consensus on biomarkers of ageing for use in intervention studies via the Delphi method.

Xenon anaesthesia is associated with a reduction in frontal electroencephalogram peak alpha frequency.

Background: Administration of conventional anaesthetic agents is associated with changes in electroencephalogram (EEG) oscillatory dynamics, including a reduction in the peak alpha frequency. Computational models of neurones can reproduce such phenomena and are valuable tools for investigating their underlying mechanisms. We hypothesised that EEG data acquired during xenon anaesthesia in humans would show similar changes in peak alpha frequency and that computational neuronal models of recognised cellular actions of xenon would be consistent with the observed changes.

Macropinocytosis controls metabolic stress-driven CAF subtype identity in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) tumors are deficient in glutamine, an amino acid that tumor cells and CAFs use to sustain their fitness. In PDAC, both cell types stimulate macropinocytosis as an adaptive response to glutamine depletion. CAFs play a critical role in sculpting the tumor microenvironment, yet how adaptations to metabolic stress impact the stromal architecture remains elusive.

Primary Central Nervous System Lymphoma Tumor Biopsies Show Heterogeneity in Gene Expression Profiles, Genetic Subtypes, and in vitro Drug Sensitivity to Kinase Inhibitors.

Primary central nervous system lymphoma (PCNSL) is clinically challenging due to its location and small biopsy size, leading to a lack of comprehensive molecular and biologic description. We previously demonstrated that 91% of PCNSL belong to the activated B-cell-like (ABC) molecular subtype of diffuse large B-cell lymphoma (DLBCL). Here we investigated the expression of 739 cancer related genes in HIV (-) patients using NanoString digital gene expression profiling in 25 ABC-PCNSL and 43 ABC-systemic DLBCL, all tumors were EBV (-).

Preoperative Biofluid Biomarkers for Predicting Postoperative Neurocognitive Disorders in Older Adults: A Systematic Review.

Preoperative biofluid biomarkers reflecting pathophysiological, neuronal injury, and inflammation as well as those for Alzheimer's disease (AD) may be valuable tools for the risk stratification of perioperative neurocognitive disorders (PNDs) in older adults. We summarized current evidence relating these preoperative biomarkers to PND beyond 7 days, in older surgical participants aged ≥60 years. Studies that evaluated the association of preoperative biomarkers with cognitive decline as an outcome, beyond 7 days, were identified through searches of 6 databases and 3 trial registries to 17 January 2024.

Tilting the Scales toward EGFR Mutant Selectivity: Expanding the Scope of Bivalent "Type V" Kinase Inhibitors.

Binding multiple sites within proteins with bivalent compounds is a strategy for developing uniquely active agents. A new class of dual-site inhibitors has emerged targeting the epidermal growth factor receptor (EGFR) anchored to both the orthosteric (ATP) and allosteric sites. Despite proof-of-concept successes, enabling selectivity against oncogenic activating mutations has not been achieved and classifying these inhibitors among kinase inhibitors remains underexplored.

Carnosine Supplementation Has No Effect on Inflammatory Markers in Adults with Prediabetes and Type 2 Diabetes: A Randomised Controlled Trial.

Background/objectives: In vitro studies suggest that carnosine reduces inflammation by upregulating anti-inflammatory mediators and downregulating pro-inflammatory cytokines. However, human clinical trials examining the effects of carnosine on inflammatory biomarkers are scant. We conducted a secondary analysis of a double-blind randomised controlled trial (RCT) to examine the effects of carnosine supplementation on inflammatory markers and adipokines in participants with prediabetes or well-controlled type 2 diabetes (T2D).

Impaired Muscle Parameters in Individuals With Premature Ovarian Insufficiency: A Pilot Study.

Context: Although bone loss is a recognized consequence of premature ovarian insufficiency (POI), the impact on skeletal muscle health is less well-defined.

Objective: To compare muscle mass and function parameters between women with POI and controls.

Methods: Cross-sectional study from a tertiary health network and community between 2017 and 2023.

Association between life satisfaction and health behaviours among older adults: a systematic review and meta-analysis protocol.

Introduction: Life satisfaction is a key indicator of successful ageing and reflects well-being. There is evidence of the association between life satisfaction and health behaviours among older adults. Therefore, this systematic review and meta-analysis protocol seeks to determine the strength and direction of the association between life satisfaction and health behaviours among older adults.

Refining Diagnostic Subtypes of Peripheral T-Cell Lymphoma Using a Multiparameter Approach.

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of neoplasms, with many cases remaining unclassifiable and categorized as PTCL-not otherwise specified (PTCL-NOS). Gene expression profiling (GEP) has delineated 2 prognostic subtypes within PTCL-NOS, PTCL-TBX21 and PTCL-GATA3, characterized by distinctive transcriptomes and a different prognosis. To further evaluate the pathologic features of these subgroups, 101 PTCL cases that did not meet specific criteria for well-defined T-cell lymphoma entities underwent detailed pathologic, immunophenotypic (including T follicular helper [T] biomarkers), and GEP analyses, separating them into PTCL-NOS (n = 63) and PTCL-TFH (also known as nodal PTCL-TFH, NOS, and TFH lymphoma, NOS) (n = 38).

Aberrant BCAT1 expression augments MTOR activity and accelerates disease progression in chronic lymphocytic leukemia.

We performed gene expression profiling of mRNA/cDNA isolated from N = 117 flow sorted CLL. We detected aberrant expression of the metabolic enzyme branched chain amino acid transferase (BCAT1) in CLL with del17p/TP53mut. Through extensive validation, we confirmed the highly preferential expression of BCAT1 in CLL with del17p/TP53mut (66%) or trisomy 12 (77%).

CNS Relapse in High-Grade B-cell Lymphoma with MYC and BCL2 Rearrangements and Dark-Zone Signature-Expressing DLBCL.

High-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH-BCL2), or 'double-hit lymphoma,' has been associated with a high risk of central nervous system (CNS) relapse. However, historic estimates are impacted by selection bias. We report CNS relapse rates associated with HGBCL-DH-BCL2 from a population-based cohort with complete fluorescence in situ hybridization testing, as well as diffuse large B-cell lymphoma morphology (DLBCL) tumors expressing the dark-zone gene expression signature (DZsig), which was originally derived from HGBCL-DH-BCL2.

A narrative review of gas separation and conservation technologies during xenon anesthesia.

Xenon gas has significant advantages over conventional general anesthetic agents but its use has been limited by the cost associated with its production. Xenon also has significant potential for medical use in the treatment of acquired brain injuries and for mental health disorders. As the demand for xenon gas from other industries increases, the costs associated with its medical use are only likely to increase.

Maximum disease diameter is associated with outcomes in stage II follicular lymphoma treated with radiation therapy alone.

Purpose: The optimal management of stage II follicular lymphoma (FL) is unclear. Radiation therapy (RT) alone has been the gold standard treatment, but a proportion of patients relapse. We sought to characterize outcomes and prognostic factors for stage II FL treated with RT alone to identify a high-risk subgroup of patients who may benefit from treatment intensification.

Extreme enthalpy‒entropy compensation in the dimerization of small solutes in aqueous solution.

This communication summarizes findings from the earliest encounters with extreme enthalpy‒entropy compensation, a phenomenon first detected in the 1950s by a reappraisal of isopiestic and calorimetric measurements on aqueous urea solutions in terms of solute self-association. Because concurrent studies of carboxylic acid association were confined to measurement of the equilibrium constant by conductance, IR spectrophotometry or potentiometric titration measurements, temperature-independence of the dimerization constant was mistakenly taken to signify a value of zero for Δ instead of (Δ  ‒ TΔ ). In those studies of small-solute self-association the extreme enthalpy‒entropy compensation was reflecting the action of water as a reactant whose hydroxyl groups were competing for the solute carbonyl involved in self-association.

MYC-rearranged mature B-cell lymphomas in children and young adults are molecularly Burkitt Lymphoma.

Aggressive B-cell non-Hodgkin lymphomas (NHL) in children, adolescents, and young adults (CAYA) include Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and a subset of high-grade tumors with features intermediate between these entities whose genetic and molecular profiles have not been completely elucidated. In this study, we have characterized 37 aggressive B-NHL in CAYA, 33 with high-grade morphology, and 4 DLBCL with MYC rearrangement (MYC-R), using targeted next-generation sequencing and the aggressive lymphoma gene expression germinal center B-cell-like (GCB), activated B-cell-like (ABC), and dark zone signatures (DZsig). Twenty-two tumors had MYC-R without BCL2 breaks, and two MYC-non-R cases had BCL6 translocations.