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C-reactive protein is a systemic inflammatory biomarker that is positively associated with the development of disease. Salivary C-reactive protein (sCRP) has previously been reported to have a diurnal rhythm with higher levels upon awakening and lower levels thereafter. The aims of this study were to evaluate the stability of sCRP across two days, characterize the daily sCRP pattern, compute morning sCRP parameters, and evaluate associations with biobehavioral health in US Navy Explosive Ordnance Disposal (EOD) technicians. Seventy male EOD technicians (ageâ¯=â¯34.9⯱â¯6.5â¯years) participated in this study, which included a tablet-based survey, measures of health and fitness, and saliva collection. In a free-living setting, participants self-collected saliva on 2 consecutive days at WAKE, WAKE+30, WAKE+60, 4p.m., and 9p.m., for a total of 10 samples. Parameters (e.g., area under the curve) were computed to characterize the morning sCRP magnitude and pattern. Pearson product-moment correlation analyses were used to assess the stability of sCRP samples and parameters across the study period and to examine associations with biobehavioral health. Average sCRP concentrations for the 2-day period were evaluated using an analysis of variance with repeated measures. The stabilities between corresponding time points on Days 1 and 2 were very high (rsâ¯=â¯0.87-.94, all psâ¯≤â¯0.001). sCRP concentrations were highest at WAKE, decreased by 73.6â¯% at WAKE+30, and then plateaued for the rest of the day. Parameters stabilities were good to excellent (rsâ¯=â¯0.77-.98, all psâ¯≤â¯0.001). We also observed associations between sCRP parameters, self-reported health behaviors, and objective measures of health and fitness. In this study of a military population, we characterized sCRP as diurnal with robust stability across 2 consecutive days, which demonstrates the feasibility of sCRP as a biomarker. These results have significant implications for study methodology and for using sCRP as a marker of dysfunction or disease.
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Cortical neurons often establish multiple synaptic contacts with the same postsynaptic neuron. To avoid functional redundancy of these parallel synapses, it is crucial that each synapse exhibits distinct computational properties. Here we model the current to the soma contributed by each synapse as a sigmoidal transmission function of its presynaptic input, with learnable parameters such as amplitude, slope, and threshold. We evaluate the classification capacity of a neuron equipped with such nonlinear parallel synapses, and show that with a small number of parallel synapses per axon, it substantially exceeds that of the Perceptron. Furthermore, the number of correctly classified data points can increase superlinearly as the number of presynaptic axons grows. When training with an unrestricted number of parallel synapses, our model neuron can effectively implement an arbitrary aggregate transmission function for each axon, constrained only by monotonicity. Nevertheless, successful learning in the model neuron often requires only a small number of parallel synapses. We also apply these parallel synapses in a feedforward neural network trained to classify MNIST images, and show that they can increase the test accuracy. This demonstrates that multiple nonlinear synapses per input axon can substantially enhance a neuron's computational power.
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PROBLEM: Preeclampsia (PE) is a hypertensive pregnancy disorder that is a leading cause of maternal and fetal morbidity and mortality characterized by maternal vascular dysfunction, oxidative stress, chronic immune activation, and excessive inflammation. No cure exists beyond delivery of the fetal-placental unit and the mechanisms driving pathophysiology are not fully understood. However, aberrant immune responses have been extensively characterized in clinical studies and shown to mediate PE pathophysiology in animal studies. One pathway that may mediate aberrant immune responses in PE is deficiencies in the IL-33 signaling pathway. In this study, we aim to investigate the impact of IL-33 signaling inhibition on cNK, TH17, and TReg populations, vascular function, and maternal blood pressure during pregnancy. METHOD OF STUDY: In this study, IL-33 signaling was inhibited using two different methods: intraperitoneal administration of recombinant ST2 (which acts as a decoy receptor for IL-33) and administration of a specific IL-33 neutralizing antibody. Maternal blood pressure, uterine artery resistance index, renal and placental oxidative stress, cNK, TH17, and TReg populations, various cytokines, and pre-proendothelin-1 levels were measured. RESULTS: IL-33 signaling inhibition increased maternal blood pressure, uterine artery resistance, placental and renal oxidative stress. IL-33 signaling inhibition also increased placental cNK and TH17 and renal TH17 cells while decreasing placental TReg populations. IL-33 neutralization increased circulating cNK and TH17s and decreased circulating TRegs in addition to increasing pre-proendothelin-1 levels. CONCLUSIONS: Data presented in this study demonstrate a role for IL-33 signaling in controlling vascular function and maternal blood pressure during pregnancy possibly by mediating innate and adaptive immune inflammatory responses, identifying the IL-33 signaling pathway as a potential therapeutic target for managing preeclampsia.
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Interleucina-33 , Pré-Eclâmpsia , Transdução de Sinais , Feminino , Gravidez , Interleucina-33/metabolismo , Pré-Eclâmpsia/imunologia , Animais , Ratos , Ratos Sprague-Dawley , Células Th17/imunologia , Modelos Animais de Doenças , Linfócitos T Reguladores/imunologia , Humanos , Estresse Oxidativo , Placenta/imunologia , Placenta/metabolismo , Pressão Sanguínea , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismoRESUMO
BACKGROUND: Recent research argues for a formalized hybrid risk assessment model that combines the current online child sex abuse risk measures with digital forensics artifacts. OBJECTIVE: We conducted a feasibility study as an initial step toward formalizing the hybrid risk assessment model by identifying high-level digital forensic artifacts that have the potential to be valid and reliable indicators of risk, with a focus on CPORT Items 5, 6, and 7. DATA: Law enforcement investigators from a High Tech Crime Unit (HTCU) randomly selected seven closed cases; selection criteria included: male offender over 18, mobile device, child sexual abuse material (CSAM) offense, and 2019-2023 index offense. Investigation details related to probable cause, final charges, conviction, and offender risk were not disclosed. Statistical information (f, %) for the following digital forensics artifacts was examined: 1) pornography collection (e.g., % of media, content type, gender ratio) and 2) evidence of networking/grooming and other problematic online activities (e.g., number of native messages vs. application messages; type of installed apps). METHOD: The analysis predicted whether the offender was a CSAM-only or dual offender and if our findings agreed with the level of risk for reoffending suggested by CPORT Items 5, 6, and 7. Results were shared with the HTCU and scored for accuracy. RESULTS: The hybrid model was accurate in 6 of 7 cases. CONCLUSION: We conclude a hybrid model is feasible, and the findings illustrate the importance of analyzing app artifacts for context. Study limitations and future research recommendations are discussed.
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Abuso Sexual na Infância , Estudos de Viabilidade , Humanos , Masculino , Medição de Risco/métodos , Criança , Abuso Sexual na Infância/diagnóstico , Criminosos , Adolescente , Adulto , Literatura EróticaRESUMO
Backpropagation (BP), a foundational algorithm for training artificial neural networks, predominates in contemporary deep learning. Although highly successful, it is often considered biologically implausible. A significant limitation arises from the need for precise symmetry between connections in the backward and forward pathways to backpropagate gradient signals accurately, which is not observed in biological brains. Researchers have proposed several algorithms to alleviate this symmetry constraint, such as feedback alignment and direct feedback alignment. However, their divergence from backpropagation dynamics presents challenges, particularly in deeper networks and convolutional layers. Here we introduce the Product Feedback Alignment (PFA) algorithm. Our findings demonstrate that PFA closely approximates BP and achieves comparable performance in deep convolutional networks while avoiding explicit weight symmetry. Our results offer a novel solution to the longstanding weight symmetry problem, leading to more biologically plausible learning in deep convolutional networks compared to earlier methods.
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The property of mixed selectivity has been discussed at a computational level and offers a strategy to maximize computational power by adding versatility to the functional role of each neuron. Here, we offer a biologically grounded implementational-level mechanistic explanation for mixed selectivity in neural circuits. We define pure, linear, and nonlinear mixed selectivity and discuss how these response properties can be obtained in simple neural circuits. Neurons that respond to multiple, statistically independent variables display mixed selectivity. If their activity can be expressed as a weighted sum, then they exhibit linear mixed selectivity; otherwise, they exhibit nonlinear mixed selectivity. Neural representations based on diverse nonlinear mixed selectivity are high dimensional; hence, they confer enormous flexibility to a simple downstream readout neural circuit. However, a simple neural circuit cannot possibly encode all possible mixtures of variables simultaneously, as this would require a combinatorially large number of mixed selectivity neurons. Gating mechanisms like oscillations and neuromodulation can solve this problem by dynamically selecting which variables are mixed and transmitted to the readout.
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Modelos Neurológicos , Neurônios , Neurônios/fisiologia , Animais , Rede Nervosa/fisiologia , Humanos , Dinâmica não LinearRESUMO
OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared with standard care resuscitation in patients with hemorrhagic shock. BACKGROUND: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury. METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at 5 US trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days versus standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality. RESULTS: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared with 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P =0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups. CONCLUSIONS AND RELEVANCE: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04667468.
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Preservação de Sangue , Transfusão de Plaquetas , Choque Hemorrágico , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Choque Hemorrágico/terapia , Choque Hemorrágico/etiologia , Preservação de Sangue/métodos , Estudos de Viabilidade , Ferimentos e Lesões/terapia , Ferimentos e Lesões/complicações , Resultado do Tratamento , Ressuscitação/métodos , Temperatura BaixaRESUMO
OBJECTIVE: To develop evidence-based guidance for topical steroid use in paediatric eosinophilic oesophagitis (pEoE) in the UK for both induction and maintenance treatment. METHODS: A systematic literature review using Cochrane guidance was carried out by the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) Eosinophilic Oesophagitis (EoE) Working Group (WG) and research leads to determine the evidence base for preparation, dosing and duration of use of swallowed topical steroid (STS) formulations in EoE. Seven themes relating to pEoE were reviewed by the WG, alongside the Cochrane review this formed the evidence base for consensus recommendations for pEoE in the UK. We provide an overview of practical considerations including treatment regimen and dosing. Oral viscous budesonide (OVB) and, if agreed by local regulatory committees, orodispersible budesonide (budesonide 1 mg tablets) were selected for ease of use and with most improvement in histology. A practical 'how to prepare and use' OVB appendix is included. Side effects identified included candidiasis and adrenal gland suppression. The use of oral systemic steroids in strictures is discussed briefly. RESULTS: 2638 citations were identified and 18 randomised controlled trials were included. Evidence exists for the use of STS for induction and maintenance therapy in EoE, especially regarding histological improvement. Using the Appraisal of Guidelines, Research and Evaluation criteria, dosing of steroids by age (0.5 mg two times per day <10 years and 1 mg two times per day ≥10 years) for induction of at least 3 months was suggested based on evidence and practical consideration. Once histological remission is achieved, maintenance dosing of steroids appears to reduce the frequency and severity of relapse, as such a maintenance weaning regimen is proposed. CONCLUSION: A practical, evidence-based flow chart and guidance recommendations with consensus from the EoE WG and education and research representatives of BSPGHAN were developed with detailed practical considerations for use in the UK.
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Budesonida , Esofagite Eosinofílica , Humanos , Esofagite Eosinofílica/tratamento farmacológico , Criança , Budesonida/administração & dosagem , Budesonida/uso terapêutico , Administração Tópica , Medicina Baseada em Evidências , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Reino Unido , Administração OralRESUMO
A central assumption of neuroscience is that long-term memories are represented by the same brain areas that encode sensory stimuli1. Neurons in inferotemporal (IT) cortex represent the sensory percept of visual objects using a distributed axis code2-4. Whether and how the same IT neural population represents the long-term memory of visual objects remains unclear. Here we examined how familiar faces are encoded in the IT anterior medial face patch (AM), perirhinal face patch (PR) and temporal pole face patch (TP). In AM and PR we observed that the encoding axis for familiar faces is rotated relative to that for unfamiliar faces at long latency; in TP this memory-related rotation was much weaker. Contrary to previous claims, the relative response magnitude to familiar versus unfamiliar faces was not a stable indicator of familiarity in any patch5-11. The mechanism underlying the memory-related axis change is likely intrinsic to IT cortex, because inactivation of PR did not affect axis change dynamics in AM. Overall, our results suggest that memories of familiar faces are represented in AM and perirhinal cortex by a distinct long-latency code, explaining how the same cell population can encode both the percept and memory of faces.
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Reconhecimento Facial , Memória de Longo Prazo , Reconhecimento Psicológico , Lobo Temporal , Animais , Face , Reconhecimento Facial/fisiologia , Macaca mulatta/fisiologia , Memória de Longo Prazo/fisiologia , Neurônios/fisiologia , Córtex Perirrinal/fisiologia , Córtex Perirrinal/citologia , Estimulação Luminosa , Reconhecimento Psicológico/fisiologia , Lobo Temporal/anatomia & histologia , Lobo Temporal/citologia , Lobo Temporal/fisiologia , RotaçãoRESUMO
How do social factors impact the brain and contribute to increased alcohol drinking? We found that social rank predicts alcohol drinking, where subordinates drink more than dominants. Furthermore, social isolation escalates alcohol drinking, particularly impacting subordinates who display a greater increase in alcohol drinking compared to dominants. Using cellular resolution calcium imaging, we show that the basolateral amygdala-medial prefrontal cortex (BLA-mPFC) circuit predicts alcohol drinking in a rank-dependent manner, unlike non-specific BLA activity. The BLA-mPFC circuit becomes hyperexcitable during social isolation, detecting social isolation states. Mimicking the observed increases in BLA-mPFC activity using optogenetics was sufficient to increase alcohol drinking, suggesting the BLA-mPFC circuit may be a neural substrate for the negative impact of social isolation. To test the hypothesis that the BLA-mPFC circuit conveys a signal induced by social isolation to motivate alcohol consumption, we first determined if this circuit detects social information. Leveraging optogenetics in combination with calcium imaging and computer vision pose tracking, we found that BLA-mPFC circuitry governs social behavior and neural representation of social contact. We further show that BLA-mPFC stimulation mimics social isolation-induced mPFC encoding of sucrose and alcohol, and inhibition of the BLA-mPFC circuit decreases alcohol drinking following social isolation. Collectively, these data suggest the amygdala-cortical circuit mirrors a neural encoding state similar to social isolation and underlies social isolation-associated alcohol drinking.
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Cellular responses to TNF are inherently heterogeneous within an isogenic cell population and across different cell types. TNF promotes cell survival by activating pro-inflammatory NF-κB and MAPK signalling pathways but may also trigger apoptosis and necroptosis. Following TNF stimulation, the fate of individual cells is governed by the balance of pro-survival and pro-apoptotic signalling pathways. To elucidate the molecular mechanisms driving heterogenous responses to TNF, quantifying TNF/TNFR1 signalling at the single-cell level is crucial. Fluorescence live-cell imaging techniques offer real-time, dynamic insights into molecular processes in single cells, allowing for detection of rapid and transient changes, as well as identification of subpopulations, that are likely to be missed with traditional endpoint assays. Whilst fluorescence live-cell imaging has been employed extensively to investigate TNF-induced inflammation and TNF-induced cell death, it has been underutilised in studying the role of TNF/TNFR1 signalling pathway crosstalk in guiding cell-fate decisions in single cells. Here, we outline the various opportunities for pathway crosstalk during TNF/TNFR1 signalling and how these interactions may govern heterogenous responses to TNF. We also advocate for the use of live-cell imaging techniques to elucidate the molecular processes driving cell-to-cell variability in single cells. Understanding and overcoming cellular heterogeneity in response to TNF and modulators of the TNF/TNFR1 signalling pathway could lead to the development of targeted therapies for various diseases associated with aberrant TNF/TNFR1 signalling, such as rheumatoid arthritis, metabolic syndrome, and cancer.
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Receptores Tipo I de Fatores de Necrose Tumoral , Fator de Necrose Tumoral alfa , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Transdução de Sinais , NF-kappa B/metabolismo , ApoptoseRESUMO
The small-molecule drug, FTY720 (fingolimod), is a synthetic sphingosine 1-phosphate (S1P) analogue currently used to treat relapsing-remitting multiple sclerosis in both adults and children. FTY720 can cross the blood-brain barrier (BBB) and, over time, accumulate in lipid-rich areas of the central nervous system (CNS) by incorporating into phospholipid membranes. FTY720 has been shown to enhance cell membrane fluidity, which can modulate the functions of glial cells and neuronal populations involved in regulating behaviour. Moreover, direct modulation of S1P receptor-mediated lipid signalling by FTY720 can impact homeostatic CNS physiology, including neurotransmitter release probability, the biophysical properties of synaptic membranes, ion channel and transmembrane receptor kinetics, and synaptic plasticity mechanisms. The aim of this study was to investigate how chronic FTY720 treatment alters the lipid composition of CNS tissue in adolescent mice at a key stage of brain maturation. We focused on the hippocampus, a brain region known to be important for learning, memory, and the processing of sensory and emotional stimuli. Using mass spectrometry-based lipidomics, we discovered that FTY720 increases the fatty acid chain length of hydroxy-phosphatidylcholine (PCOH) lipids in the mouse hippocampus. It also decreases PCOH monounsaturated fatty acids (MUFAs) and increases PCOH polyunsaturated fatty acids (PUFAs). A total of 99 lipid species were up-regulated in the mouse hippocampus following 3 weeks of oral FTY720 exposure, whereas only 3 lipid species were down-regulated. FTY720 also modulated anxiety-like behaviours in young mice but did not affect spatial learning or memory formation. Our study presents a comprehensive overview of the lipid classes and lipid species that are altered in the hippocampus following chronic FTY720 exposure and provides novel insight into cellular and molecular mechanisms that may underlie the therapeutic or adverse effects of FTY720 in the central nervous system.
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Cloridrato de Fingolimode , Hipocampo , Lipidômica , Camundongos Endogâmicos C57BL , Animais , Cloridrato de Fingolimode/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Camundongos , Masculino , Esfingosina/análogos & derivados , Esfingosina/farmacologia , Esfingosina/metabolismo , Lisofosfolipídeos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Imunossupressores/farmacologiaRESUMO
In the era of the internet of things, there exists a pressing need for technologies that meet the stringent demands of wearable, self-powered, and seamlessly integrated devices. Current approaches to developing MXene-based electrochemical sensors involve either rigid or opaque components, limiting their use in niche applications. This study investigates the potential of pristine Ti3C2Tx electrodes for flexible and transparent electrochemical sensing, achieved through an exploration of how material characteristics (flake size, flake orientation, film geometry, and uniformity) impact the electrochemical activity of the outer sphere redox probe ruthenium hexamine using cyclic voltammetry. The optimized electrode made of stacked large Ti3C2Tx flakes demonstrated excellent reproducibility and resistance to bending conditions, suggesting their use for reliable, robust, and flexible sensors. Reducing electrode thickness resulted in an amplified faradaic-to-capacitance signal, which is advantageous for this application. This led to the deposition of transparent thin Ti3C2Tx films, which maintained their best performance up to 73% transparency. These findings underscore its promise for high-performance, tailored sensors, marking a significant stride in advancing MXene utilization in next-generation electrochemical sensing technologies. The results encourage the analytical electrochemistry field to take advantage of the unique properties that pristine Ti3C2Tx electrodes can provide in sensing through more parametric studies.
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BACKGROUND: Sepsis is one of the leading causes of death. Treatment attempts targeting the immune response regularly fail in clinical trials. As HCMV latency can modulate the immune response and changes the immune cell composition, we hypothesized that HCMV serostatus affects mortality in sepsis patients. METHODS: We determined the HCMV serostatus (i.e., latency) of 410 prospectively enrolled patients of the multicenter SepsisDataNet.NRW study. Patients were recruited according to the SEPSIS-3 criteria and clinical data were recorded in an observational approach. We quantified 13 cytokines at Days 1, 4, and 8 after enrollment. Proteomics data were analyzed from the plasma samples of 171 patients. RESULTS: The 30-day mortality was higher in HCMV-seropositive patients than in seronegative sepsis patients (38% vs. 25%, respectively; p = 0.008; HR, 1.656; 95% CI 1.135-2.417). This effect was observed independent of age (p = 0.010; HR, 1.673; 95% CI 1.131-2.477). The predictive value on the outcome of the increased concentrations of IL-6 was present only in the seropositive cohort (30-day mortality, 63% vs. 24%; HR 3.250; 95% CI 2.075-5.090; p < 0.001) with no significant differences in serum concentrations of IL-6 between the two groups. Procalcitonin and IL-10 exhibited the same behavior and were predictive of the outcome only in HCMV-seropositive patients. CONCLUSION: We suggest that the predictive value of inflammation-associated biomarkers should be re-evaluated with regard to the HCMV serostatus. Targeting HCMV latency might open a new approach to selecting suitable patients for individualized treatment in sepsis.
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Infecções por Citomegalovirus , Sepse , Humanos , Citomegalovirus , Infecções por Citomegalovirus/complicações , Imunidade , Interleucina-6 , Sepse/complicaçõesRESUMO
Gene fusions involving tumor protein p63 gene (TP63) occur in multiple T and B cell lymphomas and portend a dismal prognosis for patients. The function and mechanisms of TP63 fusions remain unclear, and there is no target therapy for patients with lymphoma harboring TP63 fusions. Here, we show that TP63 fusions act as bona fide oncogenes and are essential for fusion-positive lymphomas. Transgenic mice expressing TBL1XR1::TP63, the most common TP63 fusion, develop diverse lymphomas that recapitulate multiple human T and B cell lymphomas. Here, we identify that TP63 fusions coordinate the recruitment of two epigenetic modifying complexes, the nuclear receptor corepressor (NCoR)-histone deacetylase 3 (HDAC3) by the N-terminal TP63 fusion partner and the lysine methyltransferase 2D (KMT2D) by the C-terminal TP63 component, which are both required for fusion-dependent survival. TBL1XR1::TP63 localization at enhancers drives a unique cell state that involves up-regulation of MYC and the polycomb repressor complex 2 (PRC2) components EED and EZH2. Inhibiting EZH2 with the therapeutic agent valemetostat is highly effective at treating transgenic lymphoma murine models, xenografts, and patient-derived xenografts harboring TP63 fusions. One patient with TP63-rearranged lymphoma showed a rapid response to valemetostat treatment. In summary, TP63 fusions link partner components that, together, coordinate multiple epigenetic complexes, resulting in therapeutic vulnerability to EZH2 inhibition.
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Núcleo Celular , Oncogenes , Humanos , Animais , Camundongos , Ativação Transcricional , Proteínas Correpressoras , Modelos Animais de Doenças , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Fatores de Transcrição , Proteínas Supressoras de TumorRESUMO
Introduction: The Clinical-Functional Vulnerability Index (IVCF-20) is a validated multidimensional instrument that has been used in Brazil to evaluate functional disability in frail older adults. The main aim of this study was to assess frailty using this novel screening tool. In addition, to investigate whether frailty was associated with cognitive impairment and functional disability in older adults with affective disorders. Methods: Participants included were over 60 years old, with affective disorders (depressive or anxiety disorders), from two specialized outpatient clinics. The sample was comprised of 46 patients (30% of a total from 153). The following instruments were applied: Clock Drawing Test (CDT), Mini Mental State Examination (MMSE); Verbal Fluency Test (VFT); Pfeffer Questionnaire or Functional Assessment Questionnaire (FAQ); Katz Index; Geriatric Depression Scale (GDS-15); Geriatric Anxiety Inventory (GAI), and IVCF-20 as well as sociodemographic and clinical questionnaires. The association between the variables of interest was estimated using Spearman correlation. Results: This study found a negative correlation between frailty and cognitive decline (MMSE; rs = -0.58; p < 0.001); (VFT; rs = -0.60; p < 0.001); (CDT; rs = -0.47; p = 0.001) and a positive correlation between frailty and depressive symptoms (GDS-15; rs = 0.34; p = 0.019) as well as disability for IADLs (FAQ; rs = 0.69; p < 0.001). However, there was no statistical difference in the association between frailty and anxiety symptoms (GAI; rs = 0.24; p = 0.103) or disability for BADLs (Katz; rs = -0.02; p = 0.895). Discussion: Our data support that the associations between frailty, cognitive and functional disability are prevalent issues in Psychogeriatrics. Assessing frailty in a multidimensional context is essential using a rapid assessment frailty tool in clinical practice.
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PURPOSE: Revision bariatric surgery may be undertaken after weight loss failure and/or complications following primary bariatric surgery. This study aims to compare the efficacy and safety of revision laparoscopic sleeve gastrectomy (RLSG) after gastric banding (GB) to those of primary laparoscopic sleeve gastrectomy (PLSG). MATERIALS AND METHODS: A retrospective, propensity-score matched study was conducted to compare between PLSG (control) patients and RLSG after GB (treatment) patients. Patients were matched using 2:1 nearest neighbor propensity score matching without replacement. Patients were compared on weight loss outcomes and postoperative complications for up to five years. RESULTS: 144 PLSG patients were compared against 72 RLSG patients. At 36 months, PLSG patients had significantly higher mean %TWL than RLSG patients (27.4 ± 8.6 [9.3-48.9]% vs. 17.9 ± 10.2 [1.7-36.3]%, p < 0.01). At 60 months, both groups had similar mean %TWL (16.6 ± 8.1 [4.6-31.3]% vs. 16.2 ± 6.0 [8.8-22.4)]%, p > 0.05). Early functional complication rates were slightly higher with PLSG (13.9% vs. 9.7%), but late functional complication rates were comparatively higher with RLSG (50.0% vs. 37.5%). The differences were not statistically significant (p > 0.05). Both early (0.7% vs 4.2%) and late (3.5% vs 8.3%) surgical complication rates were lower in PLSG patients compared to RLSG patients but did not reach statistical significance (p > 0.05). CONCLUSION: RLSG after GB has poorer weight loss outcomes than PLSG in the short-term. Although RLSG may carry higher risks of functional complications, the safety of RLSG and PLSG are overall comparable.
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Cirurgia Bariátrica , Derivação Gástrica , Gastroplastia , Laparoscopia , Obesidade Mórbida , Humanos , Gastroplastia/efeitos adversos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Pontuação de Propensão , Laparoscopia/efeitos adversos , Cirurgia Bariátrica/efeitos adversos , Gastrectomia/efeitos adversos , Redução de Peso , Reoperação , Resultado do TratamentoRESUMO
Motivations for understanding the underlying mechanisms of alcohol toxicity range from economical to toxicological and clinical. On the one hand, acute alcohol toxicity limits biofuel yields, and on the other hand, acute alcohol toxicity provides a vital defense mechanism to prevent the spread of disease. Herein the role that stored curvature elastic energy (SCE) in biological membranes might play in alcohol toxicity is discussed, for both short and long-chain alcohols. Structure-toxicity relationships for alcohols ranging from methanol to hexadecanol are collated, and estimates of alcohol toxicity per alcohol molecule in the cell membrane are made. The latter reveal a minimum toxicity value per molecule around butanol before alcohol toxicity per molecule increases to a maximum around decanol and subsequently decreases again. The impact of alcohol molecules on the lamellar to inverse hexagonal phase transition temperature (TH) is then presented and used as a metric to assess the impact of alcohol molecules on SCE. This approach suggests the nonmonotonic relationship between alcohol toxicity and chain length is consistent with SCE being a target of alcohol toxicity. Finally, in vivo evidence for SCE-driven adaptations to alcohol toxicity in the literature are discussed.
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Álcoois , Etanol , Álcoois/toxicidade , Metanol , Membrana Celular , TemperaturaRESUMO
Raw data obtained by ultra-high pressure liquid chromatography-mass spectrometry, and processed lipid compositional data are presented alongside detailed methodology. Data were obtained as bovine liver lipid extract oxidizes, initiated by 2,2'-Azobis(2-amidinopropane) dihydrochloride, at 0, 6 and 24 h post initiation. Lipid oxidation data in the presence and absence of some supplements with antioxidant properties was obtained. The supplements used were grape seed extract, pine bark extract, milk thistle extract, hawthorn extract and turmeric extract.
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Synaptic plasticity is a complex phenomenon involving multiple biochemical processes that operate on different timescales. Complexity can greatly increase memory capacity when the variables characterizing the synaptic dynamics have limited precision, as shown in simple memory retrieval problems involving random patterns. Here we turn to a real-world problem, face familiarity detection, and we show that synaptic complexity can be harnessed to store in memory a large number of faces that can be recognized at a later time. The number of recognizable faces grows almost linearly with the number of synapses and quadratically with the number of neurons. Complex synapses outperform simple ones characterized by a single variable, even when the total number of dynamical variables is matched. Complex and simple synapses have distinct signatures that are testable in experiments. Our results indicate that a system with complex synapses can be used in real-world tasks such as face familiarity detection.