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A deficiency of FMRP, a canonical RNA-binding protein, causes the development of Fragile X Syndrome (FXS), which is characterised by multiple phenotypes, including neurodevelopmental disorders, intellectual disability, and autism. Due to the alternative splicing of the encoding FMR1 gene, multiple FMRP isoforms are produced consisting of full-length predominantly cytoplasmic (i.e., iso1) isoforms involved in translation and truncated nuclear (i.e., iso6) isoforms with orphan functions. However, we recently implicated nuclear FMRP isoforms in DNA damage response, showing that they negatively regulate the accumulation of anaphase DNA genomic instability bridges. This finding provided evidence that the cytoplasmic and nuclear functions of FMRP are uncoupled played by respective cytoplasmic and nuclear isoforms, potentially involving specific interactions. While interaction partners of cytoplasmic FMRP have been reported, the identity of nuclear FMRP isoform partners remains to be established. Using affinity purification coupled with mass spectrometry, we mapped the nuclear interactome of the FMRP isoform iso6 in U2OS. In doing so, we found FMRP nuclear interaction partners to be involved in RNA processing, pre-mRNA splicing, ribosome biogenesis, DNA replication and damage response, chromatin remodeling and chromosome segregation. By comparing interactions between nuclear iso6 and cytoplasmic iso1, we report a set of partners that bind specifically to the nuclear isoforms, mainly proteins involved in DNA-associated processes and proteasomal proteins, which is consistent with our finding that proteasome targets the nuclear FMRP iso6. The specific interactions with the nuclear isoform 6 are regulated by replication stress, while those with the cytoplasmic isoform 1 are largely insensitive to such stress, further supporting a specific role of nuclear isoforms in DNA damage response induced by replicative stress, potentially regulated by the proteasome.

This paper presents the analytical solution of radial vibration of a rolling cylinder submitted to a time-varying point force. In the simplest situation of simply supported edges and zero in-plane vibration, the cylinder is equivalent to an orthotropic pre-stressed plate resting on a visco-elastic foundation. We give the closed-form solution of vibration as a series of normal modes whose coefficients are explicitly calculated. Cases of both deterministic and random forces are examined. We analyse the effect of rolling speed on merging of vibrational energy induced by Doppler's effect for the example of rolling tyre.

For centuries, cannabinoids have been utilized for their medicinal properties, particularly in Asian and South-Asian countries. Cannabis plants, known for their psychoactive and non-psychoactive potential, were historically used for spiritual and remedial healing. However, as cannabis became predominantly a recreational drug, it faced prohibition. Recently, the therapeutic potential of cannabinoids has sparked renewed research interest, extending their use to various medical conditions, including cancer. This review aims to highlight current data on the involvement of cannabinoids in cancer signaling pathways, emphasizing their potential in cancer therapy and the need for further investigation into the underlying mechanisms. A comprehensive literature review was conducted using databases such as PubMed/MedLine, Google Scholar, Web of Science, Scopus, and Embase. The search focused on peer-reviewed articles, review articles, and clinical trials discussing the anticancer properties of cannabinoids. Inclusion criteria included studies in English on the mechanisms of action and clinical efficacy of cannabinoids in cancer. Cannabinoids, including Δ9-THC, CBD, and CBG, exhibit significant anticancer activities such as apoptosis induction, autophagy stimulation, cell cycle arrest, anti-proliferation, anti-angiogenesis, and metastasis inhibition. Clinical trials have demonstrated cannabinoids' efficacy in tumor regression and health improvement in palliative care. However, challenges such as variability in cannabinoid composition, psychoactive effects, regulatory barriers, and lack of standardized dosing remain. Cannabinoids show promising potential as anticancer agents through various mechanisms. Further large-scale, randomized controlled trials are essential to validate these findings and establish standardized therapeutic protocols. Future research should focus on elucidating detailed mechanisms, optimizing dosing, and exploring cannabinoids as primary chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

The increasing incidence of hypospadias and cryptorchidism, coupled with the widespread presence of endocrine-disrupting chemicals (EDCs), has raised concerns about the potential impact of these environmental factors on male urogenital development. This systematic review and meta-analysis aims to evaluate the association between maternal exposure to various EDCs and the risk of hypospadias and cryptorchidism. We conducted a comprehensive search of PubMed, Scopus, Web of Science, and Cochrane databases from inception until May 2024. We included case-control and cohort studies that examined the association between maternal EDC exposure and hypospadias or cryptorchidism, reporting adjusted odds ratios (aOR) or crude odds ratios (cOR). Data were extracted and pooled using a random effects model, and heterogeneity was assessed using the Q test and I-square statistics. The risk of bias was evaluated using the Newcastle–Ottawa Scale (NOS). A total of 48 studies were included in the systematic review, with 46 studies included in the meta-analysis. The pooled analysis revealed a significant association between maternal EDC exposure and an increased risk of hypospadias (aOR = 1.26, 95% CI: 1.18–1.35, p < 0.0001) and cryptorchidism (aOR = 1.37, 95% CI: 1.19–1.57, p < 0.001). Subgroup analyses showed that exposure to pesticides, phthalates, alkyl phenolic compounds (ALKs), and heavy metals significantly increased the risk of hypospadias. In contrast, polychlorinated biphenyls (PCBs) did not show a significant association. Significant associations were found with pesticide and PCB exposure for cryptorchidism, but not with phthalate, ALK, or heavy metal exposure. Maternal exposure to certain EDCs is associated with an increased risk of hypospadias and cryptorchidism in male children. These findings underscore the importance of addressing environmental and occupational exposures during pregnancy to mitigate potential risks. Further research is needed to elucidate the mechanisms by which EDCs affect urogenital development and to develop effective interventions to reduce exposure among vulnerable populations. [ABSTRACT FROM AUTHOR]

This systematic review critically evaluates preclinical and clinical data on the antibacterial and wound healing properties of cannabinoids in integument wounds. Comprehensive searches were conducted across multiple databases, including CINAHL, Cochrane library, Medline, Embase, PubMed, Web of Science, and LILACS, encompassing records up to May 22, 2024. Eighteen studies met the inclusion criteria. Eleven were animal studies, predominantly utilizing murine models (n = 10) and one equine model, involving 437 animals. The seven human studies ranged from case reports to randomized controlled trials, encompassing 92 participants aged six months to ninety years, with sample sizes varying from 1 to 69 patients. The studies examined the effects of various cannabinoid formulations, including combinations with other plant extracts, crude extracts, and purified and synthetic cannabis-based medications administered topically, intraperitoneally, orally, or sublingually. Four animal and three human studies reported complete wound closure. Hemp fruit oil extract, cannabidiol (CBD), and GP1a resulted in complete wound closure in twenty-three (range: 5–84) days with a healing rate of 66–86% within ten days in animal studies. One human study documented a wound healing rate of 3.3 cm2 over 30 days, while three studies on chronic, non-healing wounds reported an average healing time of 54 (21–150) days for 17 patients by oral oils with tetrahydrocannabinol (THC) and CBD and topical gels with THC, CBD, and terpenes. CBD and tetrahydrocannabidiol demonstrated significant potential in reducing bacterial loads in murine models. However, further high-quality research is imperative to fully elucidate the therapeutic potential of cannabinoids in the treatment of bacterial skin infections and wounds. Additionally, it is crucial to delineate the impact of medicinal cannabis on the various phases of wound healing. This study was registered in PROSPERO (CRD42021255413). [ABSTRACT FROM AUTHOR]

In the North West Shelf region of Australia is a surface current (Holloway Current), which flows southwestward along the shelf break. This paper describes a seasonal undercurrent below the Holloway Current. A 5-day climatology is constructed from the output of an eddy-resolving oceanic general circulation model (OGCM). A seasonal northeastward-flowing undercurrent is found on the upper continental slope during the climatological April-May. This undercurrent reverses during February-March. During its annual cycle, the phase of the undercurrent tends to propagate southwestward and upward. The annual frequency dominates, but the positive and negative phases of the undercurrent are not symmetric in the yearly cycle because of the contributions from the semi-annual and 1/3-annual components. We propose a hypothesis that this undercurrent is a beam of coastal trapped wave (CTW). As an initial attempt to assess the plausibility of this hypothesis, we construct an idealized linear coastal-trapped wave (CTW) solution driven by an idealized harmonic meridional winds at the annual frequency. The solution takes the form of a beam originating from the forcing region on the continental shelf and propagating offshore and southward. When it emerges on to the continental slope, it takes the form of an undercurrent. This idealized solution shares several properties with the undercurrent in the OGCM despite several discrepancies. [ABSTRACT FROM AUTHOR]

Despite the advancements made in oncology in recent years, the treatment of pancreatic cancer remains a challenge. Five-year survival rates for this cancer do not exceed 10%. Among the reasons contributing to poor treatment outcomes are the oligosymptomatic course of the tumor, diagnostic difficulties due to the anatomical location of the organ, and the unique biological features of pancreatic cancer. The mainstay of treatment for resectable cancer is surgery and adjuvant chemotherapy. For unresectable and metastatic cancers, chemotherapy remains the primary method of treatment. At the same time, for about thirty years, there have been attempts to improve treatment outcomes by using radiotherapy combined with systemic treatment. Unlike chemotherapy, radiotherapy has no established place in the treatment of pancreatic cancer. This paper addresses the topic of radiotherapy in pancreatic cancer as a valuable method that can improve treatment outcomes alongside chemotherapy. [ABSTRACT FROM AUTHOR]

In numerous medical conditions, including pregnancy, gravity and posture interact to impact physiology and pathophysiology. Recent investigations, for example, pertaining to maternal sleeping posture during the third trimester and possible impact on fetal growth and stillbirth risk highlight the importance and potential clinical implications of the subject. In this review, we provide an extensive discussion of the impact of maternal posture on fetal physiology from conception to the postpartum period in human pregnancy. We conducted a systematic literature search of the MEDLINE database and identified 242 studies from 1991 through 2021, inclusive, that met our inclusion criteria. Herein, we provide a synthesis of the resulting literature. In the first section of the review, we group the results by the impact of maternal posture at rest on the cervix, uterus, placenta, umbilical cord, amniotic fluid, and fetus. In the second section of the review, we address the impact on fetal-related outcomes of maternal posture during various maternal activities (e.g., sleep, work, exercise), medical procedures (e.g., fertility, imaging, surgery), and labor and birth. We present the published literature, highlight gaps and discrepancies, and suggest future research opportunities and clinical practice changes. In sum, we anticipate that this review will shed light on the impact of maternal posture on fetal physiology in a manner that lends utility to researchers and clinicians who are working to improve maternal, fetal, and child health. [ABSTRACT FROM AUTHOR]

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In recent years, biopolymer-based nano-drug delivery systems with antioxidative properties have gained significant attention in the field of pharmaceutical research. These systems offer promising strategies for targeted and controlled drug delivery while also providing antioxidant effects that can mitigate oxidative stress-related diseases. Generally, the healthcare landscape is constantly evolving, necessitating the continual development of innovative therapeutic approaches and drug delivery systems (DDSs). DDSs play a pivotal role in enhancing treatment efficacy, minimizing adverse effects, and optimizing patient compliance. Among these, nanotechnology-driven delivery approaches have garnered significant attention due to their unique properties, such as improved solubility, controlled release, and targeted delivery. Nanomaterials, including nanoparticles, nanocapsules, nanotubes, etc., offer versatile platforms for drug delivery and tissue engineering applications. Additionally, biopolymer-based DDSs hold immense promise, leveraging natural or synthetic biopolymers to encapsulate drugs and enable targeted and controlled release. These systems offer numerous advantages, including biocompatibility, biodegradability, and low immunogenicity. The utilization of polysaccharides, polynucleotides, proteins, and polyesters as biopolymer matrices further enhances the versatility and applicability of DDSs. Moreover, substances with antioxidative properties have emerged as key players in combating oxidative stress-related diseases, offering protection against cellular damage and chronic illnesses. The development of biopolymer-based nanoformulations with antioxidative properties represents a burgeoning research area, with a substantial increase in publications in recent years. This review provides a comprehensive overview of the recent developments within this area over the past five years. It discusses various biopolymer materials, fabrication techniques, stabilizers, factors influencing degradation, and drug release. Additionally, it highlights emerging trends, challenges, and prospects in this rapidly evolving field. [ABSTRACT FROM AUTHOR]

Background: A novel category of unusual cannabinoid substances was created to serve as marijuana alternatives due to its widespread availability, low price, pleasurable effects, and difficulty to be detected in regular urine testing for drugs, although more potential for abuse, toxicity, and behavioral alterations can result. It is more hazardous to multiple organ systems and has higher CB1 and CB2 receptor affinities than natural cannabinoids. So, the abuse potential, toxicity, and cardiac and nervous systems health hazards of two popular street herbs (AB-PINACA and MDMB-4en-PINACA) have been evaluated in mice. Methods: Thirty male mice were separated into three equally sized groups indiscriminately: the control group: received no treatments, the AB-PINACA-treated group, and the MDMB-4en-PINACA-treated group. Treated groups were exposed to the two herbs for two consecutive days via inhalation to simulate natural human exposure. Cannabinoid tetrad tests and anxiety-like behavior were performed. Serum samples were obtained for cardiac enzymes measurement. Heart and brain tissue samples were harvested for the determination of oxidative stress markers, brain neurotransmitters, and histopathological findings. Results: Nociception and hypothermia were significantly influenced by both treatments. The locomotor activity decreased significantly with AB-PINACA inhalation, while the cataleptic effect increased significantly with MDMB-4en-PINACA inhalation. In addition, both treatments induced anxiety-like behavior. Both treatments induced alterations in brain neurotransmitter levels (glutamate, dopamine, and serotonin) and cardiac enzyme levels (CK-MB, troponin I). Histological changes showed neurodegenerative, necrotic, and infracted heart myocytes and degenerated muscle fibers, particularly with MDMB-4en-PINACA inhalation. Conclusions: Acute inhalation of street herbs containing AB-PINACA and MDMB-4en-PINACA induced neurobehavioral and cardiac disturbances, which were evident by changes in behavior, brain neurotransmitters, and heart enzymes, in addition to the degenerative histopathological changes in the brain and heart. [ABSTRACT FROM AUTHOR]

Objective(s): The process of vascular formation, also known as angiogenesis, primarily relies on endothelial cell proliferation, migration, and invasion. In recent years, it has been discovered that synthetic cannabinoids (SCs) may potentially impact angiogenic processes within the body. We evaluated the impact of the synthetic cannabinoid (R)-5-Fluoro-ADB on the proliferation rate and angiogenesis in Human Cerebral Microvascular Endothelial Cells (hBMECs). Materials and Methods: hBMECs were treated with (R)-5-Fluoro-ADB and investigated for cell viability, migration rate, and tube-like structure formation. Furthermore, angiogenic-related proteins including Angopoitein-1 and -2, and Vascular Endothelial Growth Factors (VEGF) were examined on mRNA and protein levels. Results: The results showed a notable rise in the rate of proliferation (P-value<0.0001) of HBMECs induced by (R)-5-Fluoro-ADB. The angiogenic capacity of HBMECs was also enhanced between 0.001 µM to 1 µM (R)-5-Fluoro-ADB. Moreover, an increase in the levels of ANG-1, ANG-2, and VEGF mRNA and protein, as well as elevated phosphorylation rate of GSK-3ß, were observed across various concentrations of (R)-5-Fluoro-ADB. Conclusion: Our results suggest an innovative approach in pharmacology for addressing a range of conditions linked to angiogenesis. This approach involves precise targeting of both cannabinoid receptors type-1 and -2. To achieve this, specific agonists or antagonists of these receptors could be employed based on the particular characteristics of the diseases in question. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is an obligate intracellular parasite that infects one-third of the world's human population and establishes infection in the brain. Cerebral immune cell infiltration is critical for controlling the parasite, but little is known about the molecular cues guiding immune cells to the brain during infection. Activated astrocytes produce CCL2, a chemokine that mediates inflammatory monocyte recruitment to tissues by binding to the CCR2 receptor. We detected elevated CCL2 production in the brains of C57BL/6J mice by 15 days after T. gondii infection. Utilizing confocal microscopy and intracellular flow cytometry, we identified microglia and brain-infiltrating myeloid cells as the main producers of CCL2 during acute infection, and CCL2 was specifically produced in regions of parasite infection in the brain. In contrast, astrocytes became the dominant CCL2 producer during chronic T. gondii infection. To determine the role of astrocyte-derived CCL2 in mobilizing immune cells to the brain and controlling T. gondii infection, we generated GFAP-Cre x CCL2fl/fl mice, in which astrocytes are deficient in CCL2 production. We observed significantly decreased immune cell recruitment and increased parasite burden in the brain during chronic, but not acute, infection of mice deficient in astrocyte CCL2 production, without an effect on peripheral immune responses. To investigate potential mechanisms explaining the reduced control of T. gondii infection, we analyzed key antimicrobial and immune players in host defense against T. gondii and detected a reduction in iNOS+ myeloid cells, and T. gondii-specific CD4+ T cells in the knockout mice. These data uncover a critical role for astrocyte-derived CCL2 in immune cell recruitment and parasite control in the brain during chronic, but not acute, T. gondii infection. Author summary: Neuroinflammation plays an important role in protecting the brain against infection, but it must be controlled to prevent damage to the brain. Toxoplasma gondii is an obligate intracellular foodborne parasite that infects one-third of the world's human population. Among pathogens, T. gondii has the rare ability to cross the blood-brain barrier and establish chronic infection in the brain, inducing a protective, but non-sterilizing immune response. In this study, we examined T. gondii infection of mice to understand the factors driving the neuroinflammatory response to infection of the brain. We determined that the cells producing the potent chemokine, CCL2, changed over the course of infection: myeloid cells were the main CCL2 producers during acute infection, whereas astrocytes became the dominant CCL2 producers during chronic infection. Additionally, the ablation of CCL2 production specifically from astrocytes reduced immune cell recruitment to the brain and decreased control of the parasite during chronic infection. Therefore, astrocyte-derived CCL2 plays a critical role in the control of chronic, but not acute, T. gondii infection. [ABSTRACT FROM AUTHOR]

The neurobiological mechanisms that regulate the appetite-stimulatory properties of cannabis sativa are unresolved. This work examined the hypothesis that cannabinoid-1 receptor (CB1R) expressing neurons in the mediobasal hypothalamus (MBH) regulate increased appetite following cannabis vapor inhalation. Here we utilized a paradigm where vaporized cannabis plant matter was administered passively to rodents. Initial studies in rats characterized meal patterns and operant responding for palatable food following exposure to air or vapor cannabis. Studies conducted in mice used a combination of in vivo optical imaging, electrophysiology and chemogenetic manipulations to determine the importance of MBH neurons for cannabis-induced feeding behavior. Our data indicate that cannabis vapor increased meal frequency and food seeking behavior without altering locomotor activity. Importantly, we observed augmented MBH activity within distinct neuronal populations when mice anticipated or consumed food. Mechanistic experiments demonstrated that pharmacological activation of CB1R attenuated inhibitory synaptic tone onto hunger promoting Agouti Related Peptide (AgRP) neurons within the MBH. Lastly, chemogenetic inhibition of AgRP neurons attenuated the appetite promoting effects of cannabis vapor. Based on these results, we conclude that MBH neurons contribute to the appetite stimulatory properties of inhaled cannabis. [ABSTRACT FROM AUTHOR]

A deficiency of FMRP, a canonical RNA-binding protein, causes the development of Fragile X Syndrome (FXS), which is characterised by multiple phenotypes, including neurodevelopmental disorders, intellectual disability, and autism. Due to the alternative splicing of the encoding FMR1 gene, multiple FMRP isoforms are produced consisting of full-length predominantly cytoplasmic (i.e., iso1) isoforms involved in translation and truncated nuclear (i.e., iso6) isoforms with orphan functions. However, we recently implicated nuclear FMRP isoforms in DNA damage response, showing that they negatively regulate the accumulation of anaphase DNA genomic instability bridges. This finding provided evidence that the cytoplasmic and nuclear functions of FMRP are uncoupled played by respective cytoplasmic and nuclear isoforms, potentially involving specific interactions. While interaction partners of cytoplasmic FMRP have been reported, the identity of nuclear FMRP isoform partners remains to be established. Using affinity purification coupled with mass spectrometry, we mapped the nuclear interactome of the FMRP isoform iso6 in U2OS. In doing so, we found FMRP nuclear interaction partners to be involved in RNA processing, pre-mRNA splicing, ribosome biogenesis, DNA replication and damage response, chromatin remodeling and chromosome segregation. By comparing interactions between nuclear iso6 and cytoplasmic iso1, we report a set of partners that bind specifically to the nuclear isoforms, mainly proteins involved in DNA-associated processes and proteasomal proteins, which is consistent with our finding that proteasome targets the nuclear FMRP iso6. The specific interactions with the nuclear isoform 6 are regulated by replication stress, while those with the cytoplasmic isoform 1 are largely insensitive to such stress, further supporting a specific role of nuclear isoforms in DNA damage response induced by replicative stress, potentially regulated by the proteasome. [ABSTRACT FROM AUTHOR]

The development and progression of cancer are associated with the dysregulation of multiple pathways involved in cell proliferation and survival, as well as dysfunction in redox balance, immune response, and inflammation. The master antioxidant pathway, known as the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, regulates the cellular defense against oxidative stress and inflammation, making it a promising cancer prevention and treatment target. Cannabinoids have demonstrated anti-tumor and anti-inflammatory properties, affecting signaling pathways, including Nrf2. Increased oxidative stress following exposure to anti-cancer therapy prompts cancer cells to activate antioxidant mechanisms. This indicates the dual effect of Nrf2 in cancer cells—influencing proliferation and apoptotic processes and protecting against the toxicity of anti-cancer therapy. Therefore, understanding the complex role of cannabinoids in modulating Nrf2 might shed light on its potential implementation as an anti-cancer support. In this review, we aim to highlight the impact of cannabinoids on Nrf2-related factors, with a focus on cancer prevention and treatment. Additionally, we have presented the results of several research studies that combined cannabidiol (CBD) with other compounds targeting Nrf2. Further studies should be directed toward exploring the anti-inflammatory effects of cannabinoids in the context of cancer prevention and therapy. [ABSTRACT FROM AUTHOR]

Objectives: In this study, an association between the mother's occupations with preterm and small-for-gestational-age (SGA) births was investigated using national data in Japan, and individual-level birth data from the Report of Vital Statistics: Occupational and Industrial Aspects in the 2015 fiscal year were used. Preterm and SGA birth rates were calculated for each of infant characteristics, and relative risk of each type of maternal occupations (categorized into 12 types) for the outcomes was estimated using a log binomial regression model. Results: Data of 997,600 singleton births were analyzed. Among maternal occupations, preterm birth rate was highest among carrying, cleaning, packaging, and related workers (5.65%) and lowest among security workers (4.24%). SGA birth rate was highest among manufacturing process workers (5.91%) and lowest among security workers (4.00%). We found significantly elevated risks for preterm birth among manufacturing process workers compared with unemployed mothers, and significantly elevated risks for SGA birth compared with unemployed mothers were observed among sales workers, service workers, and manufacturing process workers. In contrast, security workers had a significantly decreased risk for SGA birth compared with unemployed mothers. [ABSTRACT FROM AUTHOR]

The Surface Water and Ocean Topography (SWOT) satellite is expected to observe sea surface height (SSH) down to scales approaching ∼15 km, revealing submesoscale patterns that have never before been observed on global scales. Features at these soon‐to‐be‐observed scales, however, are expected to be significantly influenced by internal gravity waves, fronts, and other ageostrophic processes, presenting a serious challenge for estimating surface velocities from SWOT observations. Here we show that a data‐driven approach can be used to estimate the surface flow, particularly the kinematic signatures of smaller scale flows, from SSH observations, and that it performs significantly better than using the geostrophic relationship. We use a Convolutional Neural Network (CNN) trained on submesoscale‐permitting high‐resolution simulations to test the possibility of reconstructing surface vorticity, strain, and divergence from snapshots of SSH. By evaluating success using pointwise accuracy and vorticity‐strain‐divergence joint distributions, we show that the CNN works well when inertial gravity wave amplitudes are relatively weak. When the wave amplitudes are strong, reconstructions of vorticity and strain are less accurate; however, we find that the CNN naturally filters the wave‐divergence, making divergence a surprisingly reliable field to reconstruct. We also show that when applied to realistic simulations, a CNN model pretrained with simpler simulation data performs well, indicating a possible path forward for estimating real flow statistics with limited observations. Plain Language Summary: Satellite measurements of sea surface height (SSH) have for the past few decades provided weekly global estimates of upper ocean currents at scales larger than approximately 100 km. The new Surface Water and Ocean Topography satellite promises to improve the resolution of these SSH observations. However, these new observations will introduce a new challenge, since a simple physics‐based diagnostic relationship does not exist between the SSH and upper ocean currents for the finer scales that will now be visible. Here we show that a neural network can be used to estimate the surface flow from SSH observations. In particular, our trained neural networks are able to use SSH to predict aspects of upper‐ocean currents that may be particularly useful for improving estimates of oceanic transport of heat and other tracers. Key Points: Neural networks reasonably reconstruct surface vorticity, strain and divergence, from sea surface heightNeural networks naturally filter wave divergence, leaving only the desired divergence associated with frontsTransfer learning shows promise when task‐specific data is limited but data from reasonably close simulations is available [ABSTRACT FROM AUTHOR]

As the need to transition from global reliance on fossil fuels grows, solutions for producing green alternative fuels are necessary. These fuels will be especially important for hard-to-decarbonize sectors such as shipping. Mobile offshore wind energy systems (MOWESs) have been proposed as one such solution. These systems aim to harness the far-offshore wind resource, which is abundant and yet untapped because of installation and grid-connection limitations. Two classes of MOWES have been proposed in the literature: unmoored floating offshore wind turbines (UFOWTs) and energy ships (ESs). Both systems operate as autonomous power-to-X (PtX) plants, powered entirely by wind energy, and so can be used to produce synthetic green fuels such as hydrogen or ammonia, or for other energy-intensive applications such as direct air carbon capture. The two technologies differ in form; UFOWTs are based on a conventional FOWT but include propellers in place of mooring lines for course keeping, while ESs operate like a sailing ship and generate power via hydro-turbines mounted on the underside of the hull. Though much research and development is necessary for these systems to be feasible, the promise of harnessing strong winds far offshore, as well as the potential to avoid siting regulatory challenges, is enticing. This paper develops models of each MOWES concept to compare their power production on a consistent basis. The performance of the technologies is examined at steady-state operating points across relative wind speeds and angles. An optimization scheme is used to determine the values of the control variables which define the operating point for each set of environmental conditions. Results for each model show good agreement with published results for both UFOWTs and ESs. Model results suggest that UFOWTs can generate more power than ESs under ideal environmental conditions but are very sensitive to off-design operating conditions. In above-rated wind speeds, the UFOWT is able to produce as much power as a conventional, moored FOWT, whereas the ES cannot, since some power is always consumed to spin the Flettner rotors. The models developed here and their results may both be useful in future works that focus on the routing of UFOWTs or holistically designing a mobile UFOWT. Although differences in the performance of the systems have been identified, more work is necessary to discern which is a more viable producer of green electrofuels (e-fuels). [ABSTRACT FROM AUTHOR]

The article presents the discussion on etiology of testicular germ cell tumors (TGCT) suspected to be related to prenatal environmental risk factors. Topics include examining the association between parental occupational exposure to solvents and TGCT risk among their offspring; and impact of the fetal environment is also supported by large geographical variation in incidence and the evolution of TGCT incidence among migrant populations.

The current article describes the biological activity of new biomaterials combining the "green" properties of humic substances (HSs) and silver nanoparticles. The aim is to investigate the antioxidant activity (AOA) of HS matrices (macroligands) and AgNPs stabilized with humic macroligands (HS-AgNPs). The unique chemical feature of HSs makes them very promising ligands (matrices) for AgNP stabilization. HSs have previously been shown to exert many pharmacological effects mediated by their AOA. AgNPs stabilized with HS showed a pronounced ability to bind to reactive oxygen species (ROS) in the test with ABTS. Also, higher AOA was observed for HS-AgNPs as compared to the HS matrices. In vitro cytotoxicity studies have shown that the stabilization of AgNPs with the HS matrices reduces the cytotoxicity of AgNPs. As a result of in vitro experiments with the use of 2,7-dichlorodihydrofluorescein diacetate (DCFDA), it was found that all HS materials tested and the HS-AgNPs did not exhibit prooxidant effects. Moreover, more pronounced AOA was shown for HS-AgNP samples as compared to the original HS matrices. Two putative mechanisms of the pronounced AOA of the tested compositions are proposed: firstly, the pronounced ability of HSs to inactivate ROS and, secondly, the large surface area and surface-to-volume ratio of HS-AgNPs, which facilitate electron transfer and mitigate kinetic barriers to the reduction reaction. As a result, the antioxidant properties of the tested HS-AgNPs might be of particular interest for biomedical applications aimed at inhibiting the growth of bacteria and viruses and the healing of purulent wounds. [ABSTRACT FROM AUTHOR]

Cannabis remains the most illicitly produced and consumed substance worldwide, and the average trans-Δ9-tetrahydrocannabinol (THC) content in cannabis products (marijuana, hashish) has increased over time. This paper presents data about THC concentration in cannabis resin samples seized by law enforcement from 2015 to 2022 in the southern area of Rome (Italy). From 2015 to 2022, more than 1000 hashish samples were analyzed; the average THC content was 18.0% and dramatically increased from 13.7% (2015) to 27.1% (2022). The potency of THC in some samples characterized by unusual shape and color was higher than 24% and, in a few cases, higher than 40%. The age group most involved in seizures of cannabis resin concerned males aged between 15 and 36 years old. The spread of this phenomenon increases the risk of adverse health outcomes. Many observational studies compare the increased cannabis potency with the onset of psychosis, depression, anxiety and cannabis use disorders (CUDs), mainly in young adults. THC-potency monitoring provides data that can be helpful to create a network of communication and interaction between universities, and legislative and public health institutions to support education, awareness and surveillance related to cannabis abuse. [ABSTRACT FROM AUTHOR]

Cannabis enjoyed a "golden age" as a medicinal product in the late 19th, early 20th century, but the increased risk of overdose and abuse led to its criminalization. However, the 21st century have witnessed a resurgence of interest and a large body of literature regarding the benefits of cannabinoids have emerged. As legalization and decriminalization have spread around the world, cancer patients are increasingly interested in the potential utility of cannabinoids. Although eager to discuss cannabis use with their oncologist, patients often find them to be reluctant, mainly because clinicians are still not convinced by the existing evidence-based data to guide their treatment plans. Physicians should prescribe cannabis only if a careful explanation can be provided and follow up response evaluation ensured, making it mandatory for them to be up to date with the positive and also negative aspects of the cannabis in the case of cancer patients. Consequently, this article aims to bring some clarifications to clinicians regarding the sometimes-confusing various nomenclature under which this plant is mentioned, current legislation and the existing evidence (both preclinical and clinical) for the utility of cannabinoids in cancer patients, for either palliation of the associated symptoms or even the potential antitumor effects that cannabinoids may have. [ABSTRACT FROM AUTHOR]

(1) Background: Synthetic cannabinoids (SCs) are emerging drugs of abuse sold as 'K2', 'K9' or 'Spice'. Evidence shows that using SCs products leads to greater health risks than cannabis. They have been associated with greater toxicity and higher addiction potential unrelated to the primary psychoactive component of marijuana, Δ9-tetrahydrocannabinol (Δ9-THC). Moreover, early cases of intoxication and death related to SCs highlight the inherent danger that may accompany the use of these substances. However, there is limited knowledge of the toxicology of Spice ingredients. This systematic review intends to analyze the toxicity of SCs compounds in Spice/K2 drugs. (2) Methods: Studies analyzing synthetic cannabinoid toxicity and dependence were included in the present review. We searched the PubMed database of the US National Library of Medicine, Google Scholar, CompTox Chemicals, and Web of Science up to May 2022. (3) Results: Sixty-four articles reporting the effects of synthetic cannabinoids in humans were included in our review. Ten original papers and fifty-four case studies were also included. Fourteen studies reported death associated with synthetic cannabinoid use, with AB-CHMINACA and MDMB-CHMICA being the main reported SCs. Tachycardia and seizures were the most common toxicity symptoms. The prevalence of neuropsychiatric symptoms was higher in third-generation SCs. (4) Conclusion: SCs may exhibit higher toxicity than THC and longer-lasting effects. Their use may be harmful, especially in people with epilepsy and schizophrenia, because of the increased risk of the precipitation of psychiatric and neurologic disorders. Compared to other drugs, SCs have a higher potential to trigger a convulsive crisis, a decline in consciousness, and hemodynamic changes. Therefore, it is crucial to clarify their potential harms and increase the availability of toxicology data in both clinical and research settings. [ABSTRACT FROM AUTHOR]

Cannabis sativa, also known as "hemp" or "weed," is a versatile plant with various uses in medicine, agriculture, food, and cosmetics. This review attempts to evaluate the available literature on the ecology, chemical composition, phytochemistry, pharmacology, traditional uses, industrial uses, and toxicology of Cannabis sativa. So far, 566 chemical compounds have been isolated from Cannabis, including 125 cannabinoids and 198 non-cannabinoids. The psychoactive and physiologically active part of the plant is a cannabinoid, mostly found in the flowers, but also present in smaller amounts in the leaves, stems, and seeds. Of all phytochemicals, terpenes form the largest composition in the plant. Pharmacological evidence reveals that the plants contain cannabinoids which exhibit potential as antioxidants, antibacterial agents, anticancer agents, and anti-inflammatory agents. Furthermore, the compounds in the plants have reported applications in the food and cosmetic industries. Significantly, Cannabis cultivation has a minimal negative impact on the environment in terms of cultivation. Most of the studies focused on the chemical make-up, phytochemistry, and pharmacological effects, but not much is known about the toxic effects. Overall, the Cannabis plant has enormous potential for biological and industrial uses, as well as traditional and other medicinal uses. However, further research is necessary to fully understand and explore the uses and beneficial properties of Cannabis sativa. [ABSTRACT FROM AUTHOR]

This article is a discussion on the necessity of the assumption of diffuse field in statistical energy analysis and the validity of the coupling power proportionality which states that the vibrational power exchanged between coupled subsystems is proportional to the difference of their modal energies. It is proposed to re-formulate the coupling power proportionality in terms of local energy density instead of modal energy. We show that this generalized form remains valid even if the vibrational field is not diffuse. Three causes of lack of diffuseness have been studied: coherence of rays in symmetrical geometries, nonergodic geometries, and the effect of high damping. Numerical simulations and experimental results conducted on flat plates in flexural vibration are provided to support these statements. [ABSTRACT FROM AUTHOR]

Synthetic cannabinoids have exhibited unpredictable abuse liabilities, especially self-administration (SA) responses in normal rodent models, despite seemingly inducing addiction-like effects in humans. Thus, an efficient pre-clinical model must be developed to determine cannabinoid abuse potential in animals and describe the mechanism that may mediate cannabinoid sensitivity. The Cryab knockout (KO) mice were recently discovered to be potentially sensitive to the addictive effects of psychoactive drugs. Herein, we examined the responses of Cryab KO mice to JWH-018 using SA, conditioned place preference, and electroencephalography. Additionally, the effects of repeated JWH-018 exposure on endocannabinoid- and dopamine-related genes in various addiction-associated brain regions were examined, along with protein expressions involving neuroinflammation and synaptic plasticity. Cryab KO mice exhibited greater cannabinoid-induced SA responses and place preference, along with divergent gamma wave alterations, compared to wildtype (WT) mice, implying their higher sensitivity to cannabinoids. Endocannabinoid- or dopamine-related mRNA expressions and accumbal dopamine concentrations after repeated JWH-018 exposure were not significantly different between the WT and Cryab KO mice. Further analyses revealed that repeated JWH-018 administration led to possibly greater neuroinflammation in Cryab KO mice, which may arise from upregulated NF-κB, accompanied by higher expressions of synaptic plasticity markers, which might have contributed to the development of cannabinoid addiction-related behavior in Cryab KO mice. These findings signify that increased neuroinflammation via NF-κB may mediate the enhanced addiction-like responses of Cryab KO mice to cannabinoids. Altogether, Cryab KO mice may be a potential model for cannabinoid abuse susceptibility. [ABSTRACT FROM AUTHOR]

Neuropathic pain (NP) is the chronic pain in patients resulting from injuries or diseases in the somatosensory nervous system. However, effective treatment remains limited to opioids. Currently, there is an urgent need to develop new specific pharmaceuticals with low abuse potentiality. Cannabinoid receptor 2 (CB2R) is one of the significant receptors in the endocannabinoid system. It is widely expressed in the central nervous system, especially enriched in glial cells, and plays an important role in the occurrence and development of inflammation in the nervous system. CB2R activation has a neuroprotective effect on nerve injury. In this study, we report increased and more reactive microglia (with larger cell body, shorter processes, and fewer endpoints) observed in the spinal dorsal horn of spared nerve injury (SNI) rats. Continuous intrathecal administration of CB2R agonist PM226 attenuated mechanical and cold hyperalgesia in rats and prevented the transition of microglia to the proinflammatory stage. Thus, microglia transitioned into the neuroprotective stage. Meanwhile, the proinflammatory factors TNF-α and iNOS decreased, and the levels of anti-inflammatory factors Arg-1 and IL-10 increased. The content of P2X7 receptors in the spinal dorsal horn of rats increases with time after SNI. After continuous intrathecal administration of PM226, the content of P2X7 protein decreases significantly. The administration of P2X7 inhibitor A-438079 alleviated the mechanical hyperalgesia of rats, reduced the number of microglia, and decreased the content of P2X7. These results indicate that P2X7 is involved in the neuroprotective effect caused by CB2R activation. In conclusion, this study provides new insights into the neuroprotective mechanism of CB2R activation. [ABSTRACT FROM AUTHOR]

Across communities worldwide, various new psychoactive substances (NPSs) continue to emerge, which worsens the challenges to global mental health, drug rules, and public health risks, as well as combats their usage. Specifically, the vast number of NPSs that are currently available, coupled with the rate at which new ones emerge worldwide, increasingly challenges both forensic and clinical testing strategies. The well-established NPS detection techniques include immunoassays, colorimetric tests, mass spectrometric techniques, chromatographic techniques, and hyphenated types. Nonetheless, mitigating drug abuse and NPS usage is achievable through extensive community-based initiatives, with increased focus on harm reduction. Clinically validated and reliable testing of NPS from human samples, along with community-driven solution, such as harm reduction, will be of great importance, especially in combating their prevalence and the use of other illicit synthetic substances. There is a need for continued literature synthesis to reiterate the importance of NPS, given the continuous emergence of illicit substances in the recent years. All these are discussed in this overview, as we performed another look into NPS, from differentiating the major groups and identifying with laboratory testing challenges to community-based initiatives. [ABSTRACT FROM AUTHOR]

Phytocannabinoids are naturally occurring compounds, the main source of which is Cannabis sativa L. Through direct action or interaction with G protein-coupled receptors, they affect ROS and pro-inflammatory cytokines levels and modify the effectiveness of transcription factor responsible for the biosynthesis of antioxidants which lead to oxidative stress and its consequences. Due to the modification of the redox balance and inflammation, phytocannabinoids are used in the treatment of various diseases, including autoimmune dermatoses, such as atopic dermatitis and psoriasis. Psoriasis is one of the most common dermatoses, and one of unknown etiology. A disturbed redox balance with a shift towards the oxidation leads to oxidative stress, resulting in oxidative modifications, mainly of lipids and proteins, and prolonged activation of immune cells and increased generation of pro-inflammatory cytokines, resulting in chronic inflammation. Given the biological activity of phytocannabinoids, they have become the focus of research as components of pharmacotherapy for psoriasis. Beneficial effects were shown by various representatives of phytocannabinoids, but the effect of cannabidiol (CBD) on skin cells (in vitro and ex vivo) and on blood cells from patients with psoriasis vulgaris and psoriatic arthritis has been most often evaluated in recent years. [ABSTRACT FROM AUTHOR]

Several new psychoactive substances (NPS) are responsible for intoxication involving the cardiovascular and respiratory systems. Among NPS, synthetic cannabinoids (SCs) provoked side effects in humans characterized by tachycardia, arrhythmias, hypertension, breathing difficulty, apnoea, myocardial infarction, and cardiac arrest. Therefore, the present study investigated the cardio-respiratory (MouseOx Plus; EMKA electrocardiogram (ECG) and plethysmography TUNNEL systems) and vascular (BP-2000 systems) effects induced by 1-naphthalenyl (1-pentyl-1H-indol-3-yl)-methanone (JWH-018; 0.3–3–6 mg/kg) and Δ9-tetrahydrocannabinol (Δ9-THC; 0.3–3–6 mg/kg), administered in awake CD-1 male mice. The results showed that higher doses of JWH-018 (3–6 mg/kg) induced deep and long-lasting bradycardia, alternated with bradyarrhythmia, spaced out by sudden episodes of tachyarrhythmias (6 mg/kg), and characterized by ECG electrical parameters changes, sustained bradypnea, and systolic and transient diastolic hypertension. Otherwise, Δ9-THC provoked delayed bradycardia (minor intensity tachyarrhythmias episodes) and bradypnea, also causing a transient and mild hypertensive effect at the tested dose range. These effects were prevented by both treatment with selective CB1 (AM 251, 6 mg/kg) and CB2 (AM 630, 6 mg/kg) receptor antagonists and with the mixture of the antagonists AM 251 and AM 630, even if in a different manner. Cardio-respiratory and vascular symptoms could be induced by peripheral and central CB1 and CB2 receptors stimulation, which could lead to both sympathetic and parasympathetic systems activation. These findings may represent a starting point for necessary future studies aimed at exploring the proper antidotal therapy to be used in SCs-intoxicated patient management. [ABSTRACT FROM AUTHOR]

As the threat of antimicrobial-resistant bacteria compromises the safety and efficacy of modern healthcare practices, the search for effective treatments is more urgent than ever. For centuries, silver (Ag) has been known to have antibacterial properties and, over the past two decades, Ag-based nanoparticles have gained traction as potential antimicrobials. The antibacterial efficacy of Ag varies with structure, size, and concentration. In the present study, we examined Ag nanoparticles (AgNPs) for their antimicrobial activity and safety. We compared different commerciallyavailable AgNPs against gram-negative Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and gram-positive Staphylococcus aureus methicillinresistant and susceptible strains. The most effective formula of AgNPs tested had single-digit (μg/mL) minimum inhibitory concentrations against gram-negative multidrug-resistant clinical bacterial isolates with novel and emerging mechanisms of resistance. The mode of killing was assessed in E. coli and was found to be bactericidal, which is consistent with previous studies using other AgNP formulations. We evaluated cytotoxicity by measuring physiological readouts using the Caenorhabditis elegans model and found that motility was affected, but not the lifespan. Furthermore, we found that at their antibacterial concentrations, AgNPs were non-cytotoxic to any of the mammalian cell lines tested, including macrophages, stem cells, and epithelial cells. More interestingly, our experiments revealed synergy with clinically relevant antibiotics. We found that a non-toxic and non-effective concentration of AgNPs reduced the minimum inhibitory concentrations of aminoglycoside by approximately 22-fold. Because both aminoglycosides and Ag are known to target the bacterial ribosome, we tested whether Ag could also target eukaryotic ribosomes. We measured the rate of mistranslation at bactericidal concentration and found no effect, indicating that AgNPs are not proteotoxic to the host at the tested concentrations. Collectively, our results suggest that AgNPs could have a promising clinical application as a potential stand-alone therapy or antibiotic adjuvants. [ABSTRACT FROM AUTHOR]

Accidental Acute Cannabis Intoxication Presenting as Seizure in Pediatrics Patients. The frequency distribution of reported THC concentrations of legal cannabis flower products increases discontinuously around the 20% THC threshold in Nevada and Washington state. SP + sp rate (n = total #) of admissions due to epilepsy in recreational cannabis users; SP sp CUD incidence in epilepsy patients ^seizure events (N) come from the single-substance ingestion group [] concentration The authors respectfully apologize for this error. [Extracted from the article]

Objective Salivary glands of primary SS (pSS) patients characteristically harbour periductal infiltrates, in which lymphoepithelial lesions (LELs) can develop. LELs are composed of hyperplastic ductal epithelium with infiltrating lymphocytes and may assist in the challenging diagnostic process of pSS. As manual identification of LELs remains difficult, we aimed to identify LELs by using an objective digital image analysis (DIA) algorithm that detects intraepithelial lymphocytes. Methods A virtual triple-staining technique developed for this study was used to count intraepithelial lymphocytes in consecutive slides stained for CD3 (T-lymphocytes), high-molecular-weight cytokeratin (hmwCK) (striated ducts) and CD20 (B-lymphocytes) in labial and parotid gland biopsies in a diagnostic cohort of 109 sicca patients. Patients were classified as having pSS or non-SS according to the ACR-EULAR classification criteria. Results T-lymphocytes were detected in almost all analysed ducts of pSS and non-SS sicca patients, whereas intraepithelial B-lymphocytes were present in 59–68% of labial and parotid gland biopsies of pSS patients, against only 2–3% of patients classified as non-SS. Intraepithelial B-lymphocytes were found in almost all striated ducts with hyperplasia (LELs). Remarkably, ∼25% of analysed striated ducts without hyperplasia of pSS patients also contained B-lymphocytes (precursor-LELs). Furthermore, presence of intraepithelial B-lymphocytes was associated with clinical parameters of pSS (i.e. serology). Conclusion The presence of intraepithelial B-lymphocytes in salivary gland biopsies of sicca patients is a clear indicator of pSS and can be used as an objective alternative to LEL scoring. Therefore, identification of B-lymphocyte–containing ducts should be added to the diagnostic histopathological work-up of patients suspected of pSS. [ABSTRACT FROM AUTHOR]

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Purpose: The optimal time point for surgical resection of synchronous colorectal liver metastases (SCLMs) is still controversial. This meta-analysis evaluated the safety and long-term prognoses of simultaneous and staged resection of SCLM to provide a reference for clinical selection. Methods: A systematic literature search for studies published by October 2022 was performed using PubMed, Web of Science, Embase, Scopus and Cochrane Library. The evaluated outcome parameters were total, gastrointestinal and hepatic complications, as well as perioperative mortality, intraoperative blood loss, total hospital stay, 5-year disease-free survival (DFS) and 5-year overall survival (OS). Results: This meta-analysis included 22 nonrandomised and one randomised study comprising 4862 patients. The patients undergoing simultaneous resection of SCLM had similar total (OR = 0.88, 95% CI [0.66–1.19], P = 0.409), gastrointestinal (OR = 1.19, 95% CI [0.89–1.59], P = 0.241) and hepatic (OR = 1.04, 95% CI [0.83–1.31], P = 0.734) complications, as well as perioperative mortality (OR = 1.79, 95% CI [0.88–3.64], P = 0.108), 5-year DFS (HR = 1.26, 95% CI [0.96–1.66], P = 0.098) and 5-year OS (HR = 1.13, 95% CI [0.95–1.34], P = 0.164). Lower intraoperative blood loss (SMD = − 0.39, 95% CI [− 0.60 to − 0.18], P < 0.001) and shorter total hospital stay (WMD = − 5.43, 95% CI [− 7.29 to − 3.58], P < 0.001) were observed in the simultaneous-resection group versus the staged group. Conclusions: Simultaneous resection is safe and effective for SCLM patients. The long-term prognosis is equivalent to that of the traditional staged resection. Correct selection of resectable SCLM patients for the simultaneous resection of the primary tumour and liver metastases can be the first choice. Owing to the potential heterogeneity, more RCTs should be included to verify our conclusions. [ABSTRACT FROM AUTHOR]

Dysprosium barium copper oxide – bismuth sodium titanate ((1-x)DyBCO−xBNT) ceramics, where x = 0−0.07 mole fraction, were successfully prepared by a solid-state reaction and sintering method. The DyBa2Cu3O7-δ and (Bi0.5Na0.5)TiO3 powders were separately synthesized by calcining their stoichiometric mixtures at 900°C for 4 h and 800°C for 2 h, respectively. The (1-x)DyBCO−xBNT powders were compacted into pellets and sintered at 930°C for 2 h under normal air atmosphere. Phase identification and morphology of all samples were determined using X-ray diffractometer (XRD). The quantitative phase analysis was analyzed by fitting the XRD pattern using the GSAS-II program. Scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS) was used to study microstructure and chemical composition. In all cases, the result of XRD shows that the DyBa2Cu3O7–δ (Dy-123) was identified as the main crystalline phases, due to the good agreement between the observed and calculated patterns after Rietveld refinement. All BNT-doped DyBCO ceramics showed slightly higher density values than the undoped sample, suggesting that BNT helped improve the densification process. The sign of the Seebeck coefficient ( S) was positive for all samples at all measured temperatures, confirming a p-type conduction mechanism. Low BNT doping improved the overall thermoelectric properties of DyBCO ceramics by affecting electrical conductivity ( σ), Seebeck coefficient ( S), and thermal conductivity ( κ). The dimensionless figure of merit ( Z T = S 2 σ T / κ) of all samples increased with increasing temperature. The highest Z T value of 5.67 × 10−2 was observed for the 0.97DyBCO−0.03BNT sample at 863 K. [ABSTRACT FROM AUTHOR]