Fast Hadamard-Encoded 7T Spectroscopic Imaging of Human Brain.

: The increased SNR available at 7T combined with fast readout trajectories enables accelerated spectroscopic imaging acquisitions for clinical applications. In this report, we evaluate the performance of a Hadamard slice encoding strategy with a 2D rosette trajectory for multi-slice fast spectroscopic imaging at 7T. : Moderate-TE (~40 ms) spin echo and J-refocused polarization transfer sequences were acquired with simultaneous Hadamard multi-slice excitations and rosette in-plane encoding.

Modulation of Stemness and Differentiation Regulators by Valproic Acid in Medulloblastoma Neurospheres.

Changes in epigenetic processes such as histone acetylation are proposed as key events influencing cancer cell function and the initiation and progression of pediatric brain tumors. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we show that VPA reduced medulloblastoma (MB) cell viability and led to cell cycle arrest.

Chemical structure-biological activity of 1,4-naphthoquinone analogs as potential Aedes aegypti larvicides.

Background: 1,4-Naphthoquinone compounds have shown pesticidal activity against Aedes aegypti larvae, a key vector of diseases such as dengue and Zika. However, limited knowledge of their structure-activity relationships has hindered their optimization for pesticide development. This study investigates the structure-activity relationships of 1,4-naphthoquinone, particularly 2-hydroxy-1,4-naphthoquinone and its derivatives.

Exceeding the limits of paediatric heat stress tolerance: the risk of losing a generation to climate inaction.

Greenhouse gas (GHG) emissions are creating unprecedented climate-driven extreme weather, with levels of heat and humidity surpassing human physiological tolerance for heat stress. These conditions create a risk of mass casualties, with some populations particularly vulnerable due to physiological, behavioural and socioeconomic conditions (eg, lack of adequate shelter, limited healthcare infrastructure, sparse air conditioning access and electrical grid vulnerabilities). Children, especially young children, are uniquely vulnerable to extreme heat-related morbidity and mortality due to factors including low body mass, high metabolism, suboptimal thermoregulatory mechanisms and behavioural vulnerabilities.

The interplay between RNA m6A modification and radiation biology of cancerous and non-cancerous tissues: a narrative review.

The diverse radiation types in medical treatments and the natural environment elicit complex biological effects on both cancerous and non-cancerous tissues. Radiation therapy (RT) induces oncological responses, from molecular to phenotypic alterations, while simultaneously exerting toxic effects on healthy tissue. N-methyladenosine (mA), a prevalent modification on coding and non-coding RNAs, is a key epigenetic mark established by a set of evolutionarily conserved enzymes.

Quantification and prediction of human fetal (-)-Δ-tetrahydrocannabinol/(±)-11-OH-Δ-tetrahydrocannabinol exposure during pregnancy to inform fetal cannabis toxicity.

Prenatal cannabis use is associated with neurodevelopmental deficits, likely due to exposure to the psychoactive cannabinoid, (-)-Δ-tetrahydrocannabinol, and its active metabolite, (±)-11-OH-Δ-tetrahydrocannabinol. To determine causality, preclinical studies mimicking human fetal cannabinoid exposure must be conducted. Here we show cannabinoid concentrations across gestation in maternal plasma and paired fetal tissues in trimester 1 and 2 and maternal plasma and fetal umbilical venous plasma in trimester 3.

Ritlecitinib, a JAK3 /TEC inhibitor, modulates the markers of celiac autoimmunity in alopecia areata and vitiligo patients.

Background: Celiac disease (CeD) has shown an association with autoimmune disorders including vitiligo and alopecia areata (AA). Ritlecitinib, a JAK3 and TEC kinase family inhibitor, has been approved for treatment of patients with AA and is in late-stage development for vitiligo. Ritlecitinib inhibits cytotoxic T cells, NK cells, and B cells which play a role in the pathogenesis of CeD.

Prostate cancer cells elevate glycolysis and G6PD in response to caffeic acid phenethyl ester-induced growth inhibition.

Background: Caffeic acid phenethyl ester (CAPE) is the main bioactive component of poplar type propolis. We previously reported that treatment with caffeic acid phenethyl ester (CAPE) suppressed the cell proliferation, tumor growth, as well as migration and invasion of prostate cancer (PCa) cells via inhibition of signaling pathways of AKT, c-Myc, Wnt and EGFR. We also demonstrated that combined treatment of CAPE and docetaxel altered the genes involved in glycolysis and tricarboxylic acid (TCA) cycle.

Cannabidiol abrogates cue-induced anxiety associated with normalization of mitochondria-specific transcripts and linoleic acid in the nucleus accumbens shell.

Anxiety disorders are one of the top contributors to psychiatric burden worldwide. Recent years have seen a dramatic rise in the potential anxiolytic properties ascribed to cannabidiol (CBD), a non-intoxicating constituent of the Cannabis Sativa plant. This has led to several clinical trials underway to examine the therapeutic potential of CBD for anxiety disorders.

A histochemical approach to activity-based copper sensing reveals cuproplasia-dependent vulnerabilities in cancer.

Copper is an essential nutrient for sustaining vital cellular processes spanning respiration, metabolism, and proliferation. However, loss of copper homeostasis, particularly misregulation of loosely bound copper ions which are defined as the labile copper pool, occurs in major diseases such as cancer, where tumor growth and metastasis have a heightened requirement for this metal. To help decipher the role of copper in the etiology of cancer, we report a histochemical activity-based sensing approach that enables systematic, high-throughput profiling of labile copper status across many cell lines in parallel.

Not All Antiseptic Solutions Are Equivalent in Removing Biofilm: A Comparison Across Different Orthopaedic Surfaces.

Background: Antiseptic solutions are commonly utilized during total joint arthroplasty (TJA) to prevent and treat periprosthetic joint infection (PJI). The purpose of this study was to investigate which antiseptic solution is most effective against methicillin-sensitive Staphylococcus aureus (MSSA) and Escherichia coli biofilms established in vitro on orthopaedic surfaces commonly utilized in total knee arthroplasty: cobalt-chromium (CC), oxidized zirconium (OxZr), and polymethylmethacrylate (PMMA).

Methods: MSSA and E.

Modeling, synthesis and cell-based evaluation of pyridine-substituted analogs of CD3254 and fluorinated analogs of CBt-PMN as novel therapeutics.

Six pyridine analogs of (E)-3-(3-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)-4-hydroxyphenyl)acrylic acid-or CD3254 (11)-in addition to two novel analogs of 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-benzo[d][1,2,3]triazole-5-carboxylic acid (CBt-PMN or 23) were prepared and evaluated for selective retinoid-X-receptor (RXR) agonism alongside bexarotene (1), an FDA-approved drug for cutaneous T-cell lymphoma (CTCL). Treatment with 1 often elicits side-effects by disrupting or provoking other RXR-dependent nuclear receptors and cellular pathways. All analogs were assessed through modeling for their ability to bind RXR and then evaluated in human colon and kidney cells employing an RXR-RXR mammalian-2-hybrid (M2H) system and in an RXRE-controlled transcriptional assay.

Phase I Dose Volume Escalation of Rectally Administered PC-1005 to Assess Safety, Pharmacokinetics, and Antiviral Pharmacodynamics as a Multipurpose Prevention Technology (MTN-037).

Background: On demand, topical PrEP is desired by those preferring episodic, nonsystemic PrEP. PC-1005 gel (MIV-150, zinc, and carrageenan) exhibits in vitro antiviral HIV-1, human papillomavirus (HPV), and herpes simplex virus type 2 (HSV-2) activity, attractive for a multipurpose prevention technology candidate. We evaluated the safety, pharmacokinetics, and antiviral effect of rectally applied PC-1005.

Global Perspectives on Returning Genetic Research Results in Parkinson Disease.

Background And Objectives: In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable.

Proteomic signature of HIV-associated subclinical left atrial remodeling and incident heart failure.

People living with HIV are at higher risk of heart failure and associated left atrial remodeling compared to people without HIV. Mechanisms are unclear but have been linked to inflammation and premature aging. Here we obtain plasma proteomics concurrently with cardiac magnetic resonance imaging in two independent study populations to identify parallels between HIV-related and aging-related immune dysfunction that could contribute to atrial remodeling and clinical heart failure.

Using the PROMOTE Screener to Identify Psychosocial Risk Factors for Prenatal Substance Use.

Introduction: There is an urgent need to improve the identification of psychosocial vulnerabilities in clinical practice (eg, stress, unstable living conditions) and examine their contribution to prenatal substance use, especially for legal substances such as alcohol, tobacco, and recently, cannabis.

Methods: We conducted a retrospective chart review of 1842 patients who completed the PROMOTE screening instrument during their first prenatal visit to outpatient clinics of a New York State health system in 6/2019-11/2020. The PROMOTE includes 18 core items to assess psychosocial vulnerabilities including the NIDA Quick Screen assessing past year substance use.

Impulsivity behaviors and white matter mediate the relationship between genetic risk for cannabis use disorder and early cannabis use in adolescents.

Background And Aim: Cannabis use disorder (CUD) is strongly influenced by genetic factors; however the mechanisms underpinning this association are not well understood. This study investigated whether a polygenic risk score (PRS) based on a genome-wide association study for CUD in adults predicts cannabis use in adolescents and whether the association can be explained by inter-individual variation in structural properties of brain white matter or risk-taking behaviors.

Design And Setting: Longitudinal and cross-sectional analyses using data from the IMAGEN cohort, a European longitudinal study integrating genetic, neuroimaging and behavioral measures.

Divergent roles of mA in orchestrating brown and white adipocyte transcriptomes and systemic metabolism.

N-methyladenosine (mA) is among the most abundant mRNA modifications, yet its cell-type-specific regulatory roles remain unclear. Here we show that mA methyltransferase-like 14 (METTL14) differentially regulates transcriptome in brown versus white adipose tissue (BAT and WAT), leading to divergent metabolic outcomes. In humans and mice with insulin resistance, METTL14 expression differs significantly from BAT and WAT in the context of its correlation with insulin sensitivity.

Effect of Dietary Ketosis and Nicotinamide Riboside on Hippocampal Krebs Cycle Intermediates and Mitochondrial Energetics in a DNA Repair-Deficient 3xTg/POLβ Alzheimer Disease Mouse Model.

Alzheimer disease is a neurodegenerative pathology-modifying mitochondrial metabolism with energy impairments where the effects of biological sex and DNA repair deficiencies are unclear. We investigated the therapeutic potential of dietary ketosis alone or with supplemental nicotinamide riboside (NR) on hippocampal intermediary metabolism and mitochondrial bioenergetics in older male and female wild-type (Wt) and 3xTgAD-DNA polymerase-β-deficient (3xTg/POLβ) (AD) mice. DNA polymerase-β is a key enzyme in DNA base excision repair (BER) of oxidative damage that may also contribute to mitochondrial DNA repair.

Within-person affect dynamics among individuals in residential treatment for opioid use disorder: An ecological momentary assessment study.

Ecological momentary assessment is increasingly leveraged to better understand affective processes underlying substance use disorder treatment and recovery. Research in this area has yielded novel insights into the roles of mean levels of positive affect (PA) and negative affect (NA) in precipitating drug craving and substance use in daily life. Little of the extant substance use disorder treatment research, however, considers dynamic patterns of PA and NA, separately or in relation to one another, or how such patterns may differ from those observed among nonclinical samples.

evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease.

Background: Disease-modifying therapies targeting the diverse pathophysiology of Alzheimer's disease (AD), including neuroinflammation, represent potentially important and novel approaches. The glucagon-like peptide-1 receptor agonist semaglutide is approved for the treatment of type 2 diabetes and obesity and has an established safety profile. Semaglutide may have a disease-modifying, neuroprotective effect in AD through multimodal mechanisms including neuroinflammatory, vascular, and other AD-related processes.

Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer's disease in humans.

Background: Alzheimer's disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear.

Method: In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform.

Ovario- protective effect of Moringa oleifera leaf extract against cyclophosphamide-induced oxidative ovarian damage and reproductive dysfunction in female rats.

It is crucial to develop new tactics to prevent ovarian tissue damage in women whose reproductive toxicity is caused by chemotherapy. The present investigation was performed to assess the protective effects of Moringa oleifera (M. oleifera) leaf extract on cyclophosphamide (CP)-induced ovarian damage and reproductive dysfunction.

Prenatal cfDNA Sequencing and Incidental Detection of Maternal Cancer.

Background: Cell-free DNA (cfDNA) sequence analysis to screen for fetal aneuploidy can incidentally detect maternal cancer. Additional data are needed to identify DNA-sequencing patterns and other biomarkers that can identify pregnant persons who are most likely to have cancer and to determine the best approach for follow-up.

Methods: In this ongoing study we performed cancer screening in pregnant or postpartum persons who did not perceive signs or symptoms of cancer but received unusual clinical cfDNA-sequencing results or results that were nonreportable (i.

Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels.

Calcium and integrin-binding protein 2 (CIB2) and CIB3 bind to transmembrane channel-like 1 (TMC1) and TMC2, the pore-forming subunits of the inner-ear mechano-electrical transduction (MET) apparatus. These interactions have been proposed to be functionally relevant across mechanosensory organs and vertebrate species. Here, we show that both CIB2 and CIB3 can form heteromeric complexes with TMC1 and TMC2 and are integral for MET function in mouse cochlea and vestibular end organs as well as in zebrafish inner ear and lateral line.