DPYD genotype should be extended to rare variants: report on two cases of phenotype / genotype discrepancy.

The enzyme dihydropyrimidine dehydrogenase (DPD) is the primary catabolic pathway of fluoropyrimidines including 5 fluorouracil (5FU) and capecitabine. Cases of lethal toxicity have been reported in cancer patients with complete DPD deficiency receiving standard dose of 5FU or capecitabine. DPD is encoded by the pharmacogene DPYD in which more than 200 variants have been identified.

Immune transcriptomic profile in adult female pigs: dominance status has more influence than environmental enrichment.

Background: Assessing farm animals' welfare is crucial, yet practical physiological tools are still lacking. In this study, we tested whether the peripheral blood mononuclear cell (PBMC) transcriptome shows variations in association with sows' welfare. To do this, we compared animals whose welfare states were assumed to differ due to their lives in more or less enriched environments and to their different dominance statuses.

Brain endothelial permeability, transport, and flow assessed over 10 orders of magnitude using the in situ brain perfusion technique.

Background: Cerebral blood flow normally places a limit on the magnitude of brain vascular permeability (P) that can be measured in vivo. At normal cerebral blood flow, this limit falls at the lower end of lipophilicity for most FDA-approved CNS drugs. In this study, we report on two methods that can be used to overcome this limitation and measure brain vascular permeability values that are up to ~1000 times higher using the in situ brain perfusion technique.

Urea-based mutualistic transfer of nitrogen in biological soil crusts.

Foundational to establishment and recovery of biocrusts is a mutualistic exchange of carbon for nitrogen between pioneer cyanobacteria, including the widespread Microcoleus vaginatus, and heterotrophic diazotrophs in its "cyanosphere". In other such mutualisms, nitrogen is transferred as amino acids or ammonium, preventing losses through specialized structures, cell apposition or intracellularity. Yet, in the biocrust symbiosis relative proximity achieved through chemotaxis optimizes the exchange.

Responding to Trauma: A Critical Review of Mental Health and Psychosocial Interventions for Refugee Women.

Purpose Of Review: This is a critical review of English language literature (January 2023-June 2024) on psychological trauma amongst forcibly displaced migrant women. The Mental Health and Psychosocial Support (MHPSS) Framework was used to organize multi-layered mental health interventions.

Recent Findings: Findings indicate many promising community-based interventions, often delivered by trained lay facilitators.

Pleomorphic Giant Cell Carcinoma and Periurethral Abscess: A Case Report.

Prostate cancer (PCa) is the most common solid malignancy in men in the UK. Pleomorphic giant cell carcinoma (PGCC) is a rare, aggressive variant of prostate adenocarcinoma. PGCC is associated with a poor prognosis and high Gleason-grade characteristics, often occurring in patients with a history of PCa treatment.

Embracing Inclusion, Diversity, Equity and Access (IDEA): Cultivating understanding internally to foster external change.

Context: Healthcare institutions acknowledge the value of diverse workforces for enhancing programs and meeting the varied needs of individuals with Spinal Cord Injury. This survey conducted at the 2023 Academy of Spinal Cord Injury Professions (ASCIP) conference assesses healthcare professionals' views on workplace Diversity, Equity, and Inclusion (DEI) and their support for integrating related educational content in future events.

Methods: : The survey was distributed digitally to ASCIP attendees, ensuring anonymity and voluntary participation.

Discussing poverty within primary-care consultations: implications for mental health support.

Background: Poverty can have significant impacts on health and wellbeing. However, asking patients about their broader socio-economic circumstances is not routine within primary care consultations.

Aim: To understand healthcare professionals' experiences of communicating with patients about their socio-economic circumstances and how a bespoke training programme supported these conversations in routine consultations.

Investigating the formation of metal nitride complexes employing a tetradentate bis-carbene bis-phenolate ligand.

The synthesis of Mn and Cr nitride complexes of a pro-radical tetradentate bis-phenol bis-N-heterocyclic carbene ligand H2LC2O2 was investigated. Employing either azide photolysis of the Mn precursor complex MnLC2O2(N3) or a nitride exchange reaction between MnLC2O2(Br) and the nitride exchange reagent Mnsalen(N) failed to provide a useful route to the target nitride MnLC2O2(N). Experimental results support initial formation of the target nitride MnLC2O2(N), however, the nitride rapidly inserts into a Mn-C bond.

IL-17 in serum and cerebrospinal fluid of pediatric patients with acute neuropsychiatric disorders: Implications for PANDAS and PANS.

Background: Acute neuropsychiatric disorders are heterogeneous conditions resulting from interaction between genetic and environmental features. Among these, post infectious forms like Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) are common. Preclinical studies suggest a role of CNS T-helper-17/interleukin-17 (IL-17) inflammatory mediated response in the pathogenesis of these disorders.

Clinical characteristics of pediatric and adult myelin oligodendrocyte antibody-associated disease (MOGAD): A single-center study in the Northeast.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an immune-mediated, inflammatory, demyelinating disorder with a range of clinical presentations including acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), myelitis, and cerebral cortical encephalitis. Phenotypic expression of MOGAD varies with age. MOG antibody (MOG-Ab) titers at disease onset, as well as longitudinally, may predict clinical disease course.

Tumor-associated macrophages confer resistance to chemotherapy (Trifluridine/Tipiracil) in digestive cancers by overexpressing thymidine phosphorylase.

Pyrimidine analogs are part of the first-line chemotherapy regimen for gastrointestinal cancers. Trifluridine combined with tipiracil, a specific thymidine phosphorylase inhibitor, in TAS-102 has recently emerged as a potential alternative in the face of primary or secondary chemoresistance to 5-fluorouracil. Despite its promise, we report that macrophage-specific overexpression of thymidine phosphorylase results in macrophage-induced chemoresistance to TAS-102 that is insensitive to tipiracil inhibition.

Tetracycline but not sulfamethazine inhibits early root growth of wild grassland species, while seed germination is hardly affected by either antibiotic.

Seed germination and early growth of grassland species might be influenced by veterinary antibiotics that are extensively released into agricultural habitats. Therefore, we tested impacts of the commonly used antibiotics tetracycline and sulfamethazine, single and in mixture, on seed germination and seedling root growth of six typical species of temperate European grasslands (Carum carvi, Centaurea jacea, Galium mollugo, Plantago lanceolata, Silene latifolia, Dactylis glomerata). In standardised germination experiments, we assessed three germination variables (germination percentage, mean germination time, synchrony of germination) and one post-germination variable (seedling root length) under different environmentally realistic antibiotic concentrations (0.

When Do Tumours Develop? Neoplastic Processes Across Different Timescales: Age, Season and Round the Circadian Clock.

While it is recognised that most, if not all, multicellular organisms harbour neoplastic processes within their bodies, the timing of when these undesirable cell proliferations are most likely to occur and progress throughout the organism's lifetime remains only partially documented. Due to the different mechanisms implicated in tumourigenesis, it is highly unlikely that this probability remains constant at all times and stages of life. In this article, we summarise what is known about this variation, considering the roles of age, season and circadian rhythm.

Direct Synthesis of Saturated Alcohols from Conjugated Ketones Using NaBH and Catalytic Amount of CuCN in Ethanol: Additive Catalysis with a Lithium Salt or a Sodium Salt.

A direct, efficient, and highly chemoselective synthesis of saturated alcohols through one-pot sequential 1,4- and 1,2-reduction of cyclic and acyclic conjugated ketones is reported. The saturated alcohols are obtained in very good yields using sodium borohydride (NaBH) as a reducing agent and a catalytic amount of copper(I) cyanide (CuCN) in ethanol as a green solvent. This nontoxic solvent significantly favors full 1,4-reduction, as opposed to methanol.

Therapeutic Drug Monitoring of Imatinib: Is There a Rationale for Also Quantifying Its Active Metabolite?

Introduction: Therapeutic drug monitoring of imatinib is widely performed to individualize imatinib dosage. While N-desmethyl imatinib is an active metabolite of imatinib, its concentrations are not routinely determined.

Methods: Imatinib and N-desmethyl imatinib trough plasma concentrations at steady-state were obtained from 295 patients with either chronic myeloid leukemia or gastrointestinal stromal tumor to see whether N-desmethyl imatinib provided additional information.

Universal Protection of Allogeneic T-Cell Therapies from Natural Killer Cells via CD300a Agonism.

Immunogenicity limits the persistence of off-the-shelf, allogeneic cell therapies and transplants. While ablation of human leukocyte antigen (HLA) removes most T cell and humoral alloreactivity, no solution has enabled universal protection against the resulting natural killer (NK) cell response. Here, we engineered Trans Antigen Signaling Receptors (TASR) as a new class of NK inhibitory ligands and discovered CD300a, a previously inaccessible receptor, as a functional target.

Partial role of volatile organic compounds in behavioural responses of mice to bedding from cancer-affected congeners.

Tumours induce changes in body odours. We compared volatile organic compounds (VOCs) in soiled bedding of a lung adenocarcinoma male mouse model in which cancer had (CC) versus had not (NC) been induced by doxycycline at three conditions: before (T0), after 2 weeks (T2; early tumour development), after 12 weeks (T12; late tumour development) of the induction. In an earlier study, wild-derived mice behaviourally discriminated between CC and NC soiled bedding at T2 and T12.