Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in the United Kingdom: A real-world intention-to-treat analysis.

Brexucabtagene autoleucel (brexu-cel) is an autologous CD19 CAR T-cell product, approved for relapsed/refractory (r/r) mantle cell lymphoma (MCL). In ZUMA-2, brexu-cel demonstrated impressive responses in patients failing ≥2 lines, including a bruton's tyrosine kinase inhibitor, with an overall and complete response rate of 93% and 67%, respectively. Here, we report our real-world intention-to-treat (ITT) outcomes for brexu-cel in consecutive, prospectively approved patients, from 12 institutions in the United Kingdom between February 2021 and June 2023, with a focus on feasibility, efficacy, and tolerability.

Early cortical GABAergic interneurons determine the projection patterns of L4 excitatory neurons.

During cerebral cortex development, excitatory pyramidal neurons (PNs) establish specific projection patterns while receiving inputs from GABAergic inhibitory interneurons (INs). Whether these inhibitory inputs can shape PNs' projection patterns is, however, unknown. While layer 4 (L4) PNs of the primary somatosensory (S1) cortex are all born as long-range callosal projection neurons (CPNs), most of them acquire local connectivity upon activity-dependent elimination of their interhemispheric axons during postnatal development.

Outcome and feasibility of radiotherapy bridging in large B-cell lymphoma patients receiving CD19 CAR T in the UK.

Radiotherapy (RT) has potential synergistic effects with chimeric antigen receptor (CAR) T but is not widely used as bridging therapy due to logistical challenges and lack of standardised protocols. We analysed RT bridging in a multicentre national cohort of large B-cell lymphoma patients approved for 3L axicabtagene ciloleucel or tisagenlecleucel across 12 UK centres. Of 763 approved patients, 722 were leukapheresed, 717 had data available on bridging therapy.

Follistatin-like 1 (FSTL1) levels as potential early biomarker of cardiovascular disease in a Mexican population.

Cardiovascular diseases (CVD) are the leading cause of death globally. In recent years, follistatin-like protein 1 (FSTL1) has been proposed as an emerging potential clinical biomarker of CVD, since its concentration is upregulated in heart failure. The aim of the present study was to evaluate the association of FSTL1 levels and classic biomarkers with the risk of CVD in Mexican population.

Improved outcomes of large B-cell lymphoma patients treated with CD19 CAR T in the UK over time.

The success of CD19 Chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL) has been partially offset by toxicity and logistical challenges, which off-the-shelf agents like CD20xCD3 bispecific antibodies might potentially overcome. However, when using CAR T outcomes as the 'standard-of-care comparator̕ for relapsed/refractory (r/r) LBCL, a potential learning curve with implementing a novel, complex therapy like CAR T needs to be considered. To address this, we analysed 726 UK patients intended to be treated with CD19 CAR T for r/r LBCL and compared outcomes between the first year of the national CAR T programme (Era 1; 2019) and the more recent treatment era (Era 2; 2020-2022).

Dysfunctional serotonergic neuron-astrocyte signaling in depressive-like states.

Astrocytes play crucial roles in brain homeostasis and are regulatory elements of neuronal and synaptic physiology. Astrocytic alterations have been found in Major Depressive Disorder (MDD) patients; however, the consequences of astrocyte Ca signaling in MDD are poorly understood. Here, we found that corticosterone-treated juvenile mice (Cort-mice) showed altered astrocytic Ca dynamics in mPFC both in resting conditions and during social interactions, in line with altered mice behavior.

Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior.

Insulin-like growth factor-I (IGF-I) exerts multiple actions, yet the role of IGF-I from different sources is poorly understood. Here, we explored the functional and behavioral consequences of the conditional deletion of in the nervous system ( ), and demonstrated that long-term potentiation was impaired in hippocampal slices. Moreover, mice showed spatial memory deficits in the Morris water maze, and the significant sex-dependent differences displayed by mice disappeared in mice in the open field and rota-rod tests.

The situation of chlorpyrifos in Mexico: a case study in environmental samples and aquatic organisms.

Chlorpyrifos (CPF) is one of the most commonly used organophosphate pesticides. Because CPF was described as a toxic compound without safe levels of exposure for children, certain countries in Latin America and the European Union have banned or restricted its use; however, in Mexico it is used very frequently. The aim of this study was to describe the current situation of CPF in Mexico, as well as its use, commercialization, and presence in soil, water, and aquatic organisms in an agricultural region of Mexico.

CAR T in patients with large B-cell lymphoma not fit for autologous transplant.

Large B-cell lymphoma (LBCL) patients with comorbidities and/or advanced age are increasingly considered for treatment with CD19 CAR T, but data on the clinical benefit of CAR T in the less fit patient population are still limited. We analysed outcomes of consecutive patients approved for treatment with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) by the UK National CAR T Clinical Panel, according to fitness for autologous stem cell transplant (ASCT). 81/404 (20%) of approved patients were deemed unfit for ASCT.

Hematological indices as indicators of inflammation induced by exposure to pesticides.

Pesticide toxicity, both acute and chronic, is a global public health concern. Pesticides are involved in abnormal inflammatory responses by interfering with the normal physiology and metabolic status of cells. In this regard, inflammatory indices aggregate index of systemic inflammation (AISI), monocyte-to-high-density lipoprotein ratio, monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte platelet ratio (NLPR), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune inflammation index, and systemic inflammation response index (SIRI) have been used as predictive markers of inflammatory status in several diseases and also in acute poisoning events.

The Relationship between Cancer and Paraoxonase 1.

Extensive research has been carried out to understand and elucidate the mechanisms of paraoxonase 1 (PON1) in the development of diseases including cancer, cardiovascular diseases, neurological diseases, and inflammatory diseases. This review focuses on the relationship between PON1 and cancer. The data suggest that PON1, oxidative stress, chronic inflammation, and cancer are closely linked.

Methylation patterns of the and genes in an indigenous population exposed to pesticides.

The locus includes the and genes and is functionally relevant in the regulation of both cell proliferation and senescence. Studies have reported modifications of DNA methylation in this locus by exposure to environmental contaminants including pesticides; however, until now, specific methylation profiles have not been reported in genetically conserved populations exposed to occupational pesticides. The aim of this study was to determine the methylation profiles of the and genes in a genetically conserved population exposed to pesticides.

Preliminary survey of the occurrence of mycotoxins in cereals and estimated exposure in a northwestern region of Mexico.

Mycotoxins have several toxicological implications. In the present study, we evaluate the presence of aflatoxin B (AFB), ochratoxin A (OTA), and fumonisin (FB) in paddy rice, polished rice, and maize from the fields and markets in Nayarit State (Mexico). The results indicated the presence of AFB in 21.

Organophosphorus pesticide exposure biomarkers in a Mexican population.

The organophosphate (OP) pesticides are neurotoxic compounds widely used around the world. Evaluation of OP exposure in human studies is important for enabling adequate data analyses and drawing accurate conclusions. The aim of this study was to analyze OP exposure biomarkers and their relationships in a Mexican population with different exposure levels.

Metabolic Changes in Brain Slices over Time: a Multiplatform Metabolomics Approach.

Brain slice preparations are widely used for research in neuroscience. However, a high-quality preparation is essential and there is no consensus regarding stable parameters that can be used to define the status of the brain slice preparation after its collection at different time points. Thus, it is critical to fully characterize the experimental conditions for ex vivo studies using brain slices for electrophysiological recording.

Environmental and socio-cultural impacts on global DNA methylation in the indigenous Huichol population of Nayarit, Mexico.

Alterations of global DNA methylation have been evaluated in several studies worldwide; however, Long Interspersed Nuclear Elements-1 (LINE-1) methylation in genetically conserved populations such as indigenous communities have not, to our knowledge, been reported. The aim of this study was to evaluate the relationship between LINE-1 methylation patterns and factors such as pesticide exposure and socio-cultural characteristics in the Indigenous Huichol Population of Nayarit, Mexico. A cross-sectional study was conducted in 140 Huichol indigenous individuals.

PON1 status and homocysteine levels as potential biomarkers for cardiovascular disease.

Background: Cardiovascular disease (CVD) is the leading cause of death. The mainly risks factors for CVD are diabetes, hypertension and high levels of homocysteine (Hcys), among others. Paraoxonase 1 (PON1) has been proposed as an antiatherogenic target for its ability to hydrolyzing oxi-Low-Density-Lipoproteins (LDL) and Hcys-thiolactone.

Melanopsin for Time-Controlling Activation of Astrocyte -Neuron Networks.

Melanopsin, a mammalian G-protein-coupled photopigment, is a novel optical tool which enables studying astrocyte-neuron networks. Here, we describe the required guidelines to take advantage of this promising optical tool for functional neuron-glia studies. The selective expression of melanopsin in astrocytes allows triggering astrocytic Ca signaling, changes in synaptic transmission, and modifying behavioral responses.

Relationship between butyrylcholinesterase activity and lipid parameters in workers occupationally exposed to pesticides.

Exposure to organophosphate pesticides (OP) has been associated with the inhibition of cholinesterase enzymatic activity, such as butyrylcholinesterase (BuChE). Changes in BuChE activity have been associated with obesity, diabetes, hyperthyroidism, and metabolic syndrome. However, few studies have evaluated the effects of pesticides on both BuChE and lipid parameters.

Sex-dependent calcium hyperactivity due to lysosomal-related dysfunction in astrocytes from APOE4 versus APOE3 gene targeted replacement mice.

Background: The apolipoprotein E (APOE) gene exists in three isoforms in humans: APOE2, APOE3 and APOE4. APOE4 causes structural and functional alterations in normal brains, and is the strongest genetic risk factor of the sporadic form of Alzheimer's disease (LOAD). Research on APOE4 has mainly focused on the neuronal damage caused by defective cholesterol transport and exacerbated amyloid-β and Tau pathology.

Mutant Calreticulin in the Myeloproliferative Neoplasms.

Mutations in the gene for calreticulin () were identified in the myeloproliferative neoplasms (MPNs) essential thrombocythaemia (ET) and primary myelofibrosis (MF) in 2013; in combination with previously described mutations in and , driver mutations have now been described for the majority of MPN patients. In subsequent years, researchers have begun to unravel the mechanisms by which mutant CALR drives transformation and to understand their clinical implications. Mutant CALR activates the thrombopoietin receptor (MPL), causing constitutive activation of Janus kinase 2 (JAK2) signaling and cytokine independent growth in vitro.

Phenotypes and concentration of PON1 in cardiovascular disease: The role of nutrient intake.

Background And Aims: Paraoxonase 1 (PON1) is considered to play a crucial role as an anti-atherosclerotic factor. The PON1 activity is affected by genetic polymorphisms, environmental factors, age, sex, lifestyle, pharmaceutical drugs, and dietary factors. The aim of this study was to evaluate the association between macro- and micronutrients as well as PON1 concentration and activities in patients with cardiovascular diseases (CVD), cardiovascular risk factors but no CVD (CRF), and in healthy controls (control group).

PON1 lactonase activity and its association with cardiovascular disease.

Background: Paraoxonase 1 (PON1) is important in the development of atherosclerosis, and it has become the subject of intensive research. Our aim was to evaluate the association of serum PON1 activity and polymorphisms with cardiovascular disease (CVD) using four different substrates.

Materials And Methods: Activity of PON1-related to arylesterase (AREase and 4-CMPAse), paraoxonase (PONase), and lactonase (LACase), and polymorphisms (A-162G, T-108C, L55M, and Q192R) were evaluated in subjects with CVD, cardiovascular risk factor (CFR), and controls.