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1.
Blood Adv ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008716

RESUMO

Central nervous system (CNS) involvement remains a clinical hurdle in treating childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The disease mechanisms of CNS leukemia are primarily investigated using 2D cell culture and mouse models. Given the variations in cellular identity and architecture between the human and murine CNS, it becomes imperative to seek complementary models to study CNS leukemia. Here, we present a first-of-its-kind 3D co-culture model combining human brain organoids and BCP-ALL-cells. We noticed significantly higher engraftment of BCP-ALL cell lines and patient-derived xenograft (PDX) cells in cerebral organoids as compared to non-ALL-cells. To validate translatability between organoid co-culture and in vivo murine models, we confirmed that targeting CNS leukemia relevant pathways like CD79a/Igα or CXCR4-SDF1 reduced the invasion of BCP-ALL-cells into organoids. RNA sequencing and functional validations of organoid-invading leukemia cells compared to the non-invaded fraction revealed significant upregulation of AP-1 transcription factor-complex members in organoid-invading cells. Moreover, we detected a significant enrichment of AP-1 pathway genes in ALL-PDX-cells recovered from the CNS compared to spleen blasts of mice transplanted with TCF3::PBX1+ PDX-cells, substantiating the role of AP-1 signaling in CNS disease. Accordingly, we found significantly higher levels of the AP-1-gene JUN in patients initially diagnosed as CNS-positive compared to CNS-negative cases as well as CNS-relapse vs non-CNS-relapse cases in a cohort of 100 BCP-ALL-patients. Our results suggest CNS-organoids as a novel model to investigate CNS-involvement and identify the AP-1 pathway as a critical driver of CNS-disease in BCP-ALL.

2.
Biochimie ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38857695

RESUMO

Uropathogenic strains of E. coli (UPEC) is a leading cause of sepsis, deploying multiple virulence factors to evade host immune responses. Notably, alpha-hemolysin (HlyA) produced by UPEC is implicated in septic symptoms associated with bacteremia, correlating with thrombocytopenia, a critical indicator of organ dysfunction and a predictor of poorer patient prognosis. This study meticulously explores the impact of sublytic concentrations of HlyA on platelets. Findings reveal that HlyA triggers an increase in intracellular calcium, activating calpain and exposing phosphatidylserine to the cell surface, as validated by flow cytometric experiments. Electron microscopy reveals a distinctive balloon-like shape in HlyA-treated platelets, indicative of a procoagulant state. The toxin induces the release of procoagulant extracellular vesicles and the secretion of alpha and dense granules. Overall, the results point to HlyA inducing a necrotic-like procoagulant state in platelets. The effects of sublytic concentrations of HlyA on both erythrocytes and platelets could have a potential impact on capillary microcirculation. Targeting HlyA emerges as a viable therapeutic strategy to mitigate the adverse effects of UPEC infections, especially in South American countries where these infections are endemic, underscoring its significance as a potential therapeutic target.

3.
Sensors (Basel) ; 24(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38894353

RESUMO

The paper introduces a computer vision methodology for detecting pitting corrosion in gas pipelines. To achieve this, a dataset comprising 576,000 images of pipelines with and without pitting corrosion was curated. A custom-designed and optimized convolutional neural network (CNN) was employed for binary classification, distinguishing between corroded and non-corroded images. This CNN architecture, despite having relatively few parameters compared to existing CNN classifiers, achieved a notably high classification accuracy of 98.44%. The proposed CNN outperformed many contemporary classifiers in its efficacy. By leveraging deep learning, this approach effectively eliminates the need for manual inspection of pipelines for pitting corrosion, thus streamlining what was previously a time-consuming and cost-ineffective process.

4.
Mar Pollut Bull ; 204: 116561, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38838392

RESUMO

In 2015, > 460,000 L of aqueous film-forming foam (AFFF) and fire suppressors containing per- and polyfluoroalkyl substances (PFAS) were used to combat a fire at a petrochemical fuel storage terminal in the Port of Santos (Brazil). Sediments from seven sites were sampled repeatedly from 2 weeks to 1 year after the fire (n = 30). Æ©15PFAS concentrations ranged from 115 to 15,931 pg g-1 dry weight (dw). Perfluorooctane sulfonic acid (PFOS) was the most frequently detected compound with concentrations ranging from 363 to 4517 (average = 1603) pg g-1dw to <47.1 to 642 (average = 401) pg g-1 dw, followed by perfluorohexanoic acid (PFHxA) (from 38.8 to 219 (average = 162) pg g-1 dw after 15 days and from <20.8 to 161 (average = 101) pg g-1 dw one year later). Together, the hydrodynamics and fire events documented in the region were important features explaining the spread of PFAS.


Assuntos
Ácidos Alcanossulfônicos , Monitoramento Ambiental , Fluorocarbonos , Poluentes Químicos da Água , Fluorocarbonos/análise , Poluentes Químicos da Água/análise , Ácidos Alcanossulfônicos/análise , Brasil , Sedimentos Geológicos/química , Caproatos/análise
5.
Water Res ; 258: 121803, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38795548

RESUMO

Nano zero-valent metals (nZVMs) have been extensively utilized for decades in the reductive remediation of groundwater contaminated with chlorinated organic compounds, owing to their robust reducing capabilities, simple application, and cost-effectiveness. Nevertheless, there remains a dearth of information regarding the efficient reductive defluorination of linear or branched per- and polyfluoroalkyl substances (PFASs) using nZVMs as reductants, largely due to the absence of appropriate catalysts. In this work, various soluble porphyrin ligands [[meso­tetra(4-carboxyphenyl)porphyrinato]cobalt(III)]Cl·7H2O (CoTCPP), [[meso­tetra(4-sulfonatophenyl) porphyrinato]cobalt(III)]·9H2O (CoTPPS), and [[meso­tetra(4-N-methylpyridyl) porphyrinato]cobalt(II)](I)4·4H2O (CoTMpyP) have been explored for defluorination of PFASs in the presence of the nZn0 as reductant. Among these, the cationic CoTMpyP showed best defluorination efficiencies for br-perfluorooctane sulfonate (PFOS) (94%), br-perfluorooctanoic acid (PFOA) (89%), and 3,7-Perfluorodecanoic acid (PFDA) (60%) after 1 day at 70 °C. The defluorination rate constant of this system (CoTMpyP-nZn0) is 88-164 times higher than the VB12-nZn0 system for the investigated br-PFASs. The CoTMpyP-nZn0 also performed effectively at room temperature (55% for br-PFOS, 55% for br-PFOA and 25% for 3,7-PFDA after 1day), demonstrating the great potential of in-situ application. The effect of various solubilizing substituents, electron transfer flow and corresponding PFASs defluorination pathways in the CoTMpyP-nZn0 system were investigated by both experiments and density functional theory (DFT) calculations. SYNOPSIS: Due to the unavailability of active catalysts, available information on reductive remediation of PFAS by zero-valent metals (ZVMs) is still inadequate. This study explores the effective defluorination of various branched PFASs using soluble porphyrin-ZVM systems and offers a systematic approach for designing the next generation of catalysts for PFAS remediation.


Assuntos
Zinco , Zinco/química , Porfirinas/química , Fluorocarbonos/química , Metaloporfirinas/química , Poluentes Químicos da Água/química , Oxirredução
6.
Rev Mal Respir ; 41(6): 451-454, 2024 Jun.
Artigo em Francês | MEDLINE | ID: mdl-38796386

RESUMO

Targeted therapies are the standard first-line treatment for metastatic lung adenocarcinoma with certain molecular abnormalities. These abnormalities are particularly common in Southeast Asia and French Polynesia. A 51-year-old Tahitian female non-smoker was diagnosed in 2018 with stage IV lung adenocarcinoma harboring a p.L858R EGFR mutation. She received gefitinib as first-line treatment. Due to locoregional progression and the presence of a resistance mutation (p.T790M of EFGR), she received osimertinib as second-line treatment, after which chemotherapy was proposed as 3rd-line treatment. An additional biopsy detected not only the previously known EGFR mutation, but also a BRAF p.V600E mutation. Following disease progression during chemotherapy, the patient received targeted therapies combining dabrafenib, trametinib and osimertinib. Due to a dissociated response after four months of treatment, a 5th line of paclitaxel bevacizumab was initiated. Subsequent to additional progression and given the ALK rearrangement shown on the re-biopsy, 6th-line treatment with alectinib was proposed. As the response was once again dissociated, a final line was proposed before stopping active treatments due to their toxicity and overall deterioration in the patient's state of health. This exceptional case is characterized by resistance to anti-EGFR through the successive and cumulative acquisition of two new oncogene addictions. The authors underline the importance of re-biopsy at each progression, leading (if at all feasible) to yet around round of targeted therapy.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Neoplasias Pulmonares , Vício Oncogênico , Feminino , Humanos , Pessoa de Meia-Idade , Acrilamidas/uso terapêutico , Acrilamidas/farmacologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Compostos de Anilina/uso terapêutico , Compostos de Anilina/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Receptores ErbB/genética , Gefitinibe/uso terapêutico , Gefitinibe/farmacologia , Indóis , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Pirimidinas
7.
Mar Pollut Bull ; 203: 116386, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703625

RESUMO

Ecotoxicological tools, namely biomarkers and bioassays, may provide insights on the ecological quality status of mangroves under restoration. We investigated how 1) physicochemical parameters and water bioassays using Artemia franciscana; and 2) quantification of sublethal (osmoregulatory capacity, biochemical, and oxidative stress) and individual biomarkers (density, length-weight relationship [LWR], parasitic prevalence) in the sentinel fiddler crab Minuca rapax, can improve restoration indicators in mangroves from the Yucatán Peninsula, Southern Gulf of Mexico. We showed that water quality was improved with restoration, but still presented toxicity. Regarding sublethal biomarkers, M rapax from restored areas lower osmotic regulatory capacity, higher oxidative stress, and showed lipid peroxidation. As to the individual biomarkers, the density, LWR, and the prevalence of parasites in M. rapax was higher in restored areas. The use of bioassays/biomarkers were useful as early warning indicators to better assess the health of mangroves under restoration.


Assuntos
Ecotoxicologia , Monitoramento Ambiental , Áreas Alagadas , Animais , México , Monitoramento Ambiental/métodos , Biomarcadores , Braquiúros , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Qualidade da Água , Artemia , Bioensaio , Recuperação e Remediação Ambiental , Estresse Oxidativo , Golfo do México
8.
Artigo em Inglês | MEDLINE | ID: mdl-38734817

RESUMO

Considerable research has linked relative reduction in the amplitude of the P3 event-related potential (ERP) during cognitive task performance (i.e., Target-P3) with increased risk of alcohol-related problems. A separate literature indicates that a relative increase in the amplitude of the P3 elicited by cues signaling alcohol availability (i.e., ACR-P3) also is associated with alcohol use and problems. To date, no research has integrated these seemingly discrepant findings. Here, we aimed to demonstrate that P3 amplitudes elicited in different task contexts reflect distinct domains of functioning relevant to problematic alcohol involvement (PAI), and therefore can inform heterogeneity in the etiology of PAI. 156 emerging adults (61% women; 88% White/Non-Hispanic) completed a mental rotation task and a picture-viewing task while ERPs were recorded. Participants also completed questionnaire measures of trait disinhibition, alcohol use, and alcohol-related problems. Findings from regression analyses indicated that (a) Target-P3 was negatively associated and ACR-P3 was positively associated with a PAI latent variable; (b) the two P3s accounted for unique variance in PAI, beyond that accounted for by recent drinking; and (c) the association between Target-P3 and PAI-but not ACR-P3 and PAI-was statistically mediated by trait disinhibition. The present findings highlight the unique contributions of distinct functional domains associated with disinhibition and incentive salience in the etiology of PAI. Moreover, findings are consistent with a nuanced understanding of the P3 ERP, whereby its specific meaning varies according to the task context in which it is elicited.

10.
J Stud Alcohol Drugs ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563280

RESUMO

OBJECTIVE: Perception of others' approval of alcohol use (i.e., injunctive drinking norms) is strongly predictive of alcohol use, particularly among young adults (Krieger et al., 2016). While between-person injunctive norms predict alcohol use (Neighbors et al., 2008), there is evidence of within-person fluctuations in the relationship between norms and drinking (Graupensperger et al., 2021). The current study used ecological momentary assessment (EMA) to test within-person, day-level associations between injunctive norms and alcohol use, and to test whether social context moderated this association. METHOD: Participants (n=83, M age=24.0, 50.9% female) completed a two-week EMA protocol using a smartphone application. Injunctive norms, social context (type and gender of companions), and number of drinks consumed were assessed each morning following a drinking event. Multilevel models with repeated measures nested within participants tested main effects and interactions of between- and within-person injunctive norms, type of drinking companions, and gender of drinking companions on number of drinks consumed. RESULTS: Day-level injunctive norms were positively associated with drinking quantity over and above baseline norms. The effect of norms differed by social context such that norms were only positively related to drinking quantity when drinking with a friend or romantic partner (vs. drinking alone). Gender of friends with whom participants drank did not moderate the effect of norms on quantity. CONCLUSIONS: This study provides one of the first examinations of daily fluctuations in injunctive drinking norms. As norms represent a malleable target for intervention (White et al., 2019), results offer new information regarding possible intervention targets.

11.
Glob Chang Biol ; 30(4): e17274, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38605677

RESUMO

Climate change and other anthropogenic disturbances are increasing liana abundance and biomass in many tropical and subtropical forests. While the effects of living lianas on species diversity, ecosystem carbon, and nutrient dynamics are receiving increasing attention, the role of dead lianas in forest ecosystems has been little studied and is poorly understood. Trees and lianas coexist as the major woody components of forests worldwide, but they have very different ecological strategies, with lianas relying on trees for mechanical support. Consequently, trees and lianas have evolved highly divergent stem, leaf, and root traits. Here we show that this trait divergence is likely to persist after death, into the afterlives of these organs, leading to divergent effects on forest biogeochemistry. We introduce a conceptual framework combining horizontal, vertical, and time dimensions for the effects of liana proliferation and liana tissue decomposition on ecosystem carbon and nutrient cycling. We propose a series of empirical studies comparing traits between lianas and trees to answer questions concerning the influence of trait afterlives on the decomposability of liana and tree organs. Such studies will increase our understanding of the contribution of lianas to terrestrial biogeochemical cycling, and help predict the effects of their increasing abundance.


Assuntos
Ecossistema , Clima Tropical , Florestas , Árvores , Carbono
12.
Blood ; 143(26): 2735-2748, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38518105

RESUMO

ABSTRACT: Acute lymphoblastic leukemia (ALL) arises from the uncontrolled proliferation of B-cell precursors (BCP-ALL) or T cells (T-ALL). Current treatment protocols obtain high cure rates in children but are based on toxic polychemotherapy. Novel therapies are urgently needed, especially in relapsed/refractory (R/R) disease, high-risk (HR) leukemias and T-ALL, in which immunotherapy approaches remain scarce. Although the interleukin-7 receptor (IL-7R) plays a pivotal role in ALL development, no IL-7R-targeting immunotherapy has yet reached clinical application in ALL. The IL-7Rα chain (CD127)-targeting IgG4 antibody lusvertikimab (LUSV; formerly OSE-127) is a full antagonist of the IL-7R pathway, showing a good safety profile in healthy volunteers. Here, we show that ∼85% of ALL cases express surface CD127. We demonstrate significant in vivo efficacy of LUSV immunotherapy in a heterogeneous cohort of BCP- and T-ALL patient-derived xenografts (PDX) in minimal residual disease (MRD) and overt leukemia models, including R/R and HR leukemias. Importantly, LUSV was particularly effective when combined with polychemotherapy in a phase 2-like PDX study with CD127high samples leading to MRD-negativity in >50% of mice treated with combination therapy. Mechanistically, LUSV targeted ALL cells via a dual mode of action comprising direct IL-7R antagonistic activity and induction of macrophage-mediated antibody-dependent cellular phagocytosis (ADCP). LUSV-mediated in vitro ADCP levels significantly correlated with CD127 expression levels and the reduction of leukemia burden upon treatment of PDX animals in vivo. Altogether, through its dual mode of action and good safety profile, LUSV may represent a novel immunotherapy option for any CD127+ ALL, particularly in combination with standard-of-care polychemotherapy.


Assuntos
Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Humanos , Camundongos , Receptores de Interleucina-7/antagonistas & inibidores , Camundongos SCID , Fagocitose/efeitos dos fármacos , Subunidade alfa de Receptor de Interleucina-7 , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Feminino , Camundongos Endogâmicos NOD , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Linhagem Celular Tumoral , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico
13.
Hemasphere ; 8(2): e48, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38435424

RESUMO

CD19-directed immunotherapy has become a cornerstone in the therapy of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). CD19-directed cellular and antibody-based therapeutics have entered therapy of primary and relapsed disease and contributed to improved outcomes in relapsed disease and lower therapy toxicity. However, efficacy remains limited in many cases due to a lack of therapy response, short remission phases, or antigen escape. Here, BCP-ALL cell lines, patient-derived xenograft (PDX) samples, human macrophages, and an in vivo transplantation model in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice were used to examine the therapeutic potency of a CD19 antibody Fc-engineered for improved effector cell recruitment (CD19-DE) and antibody-dependent cellular phagocytosis (ADCP), in combination with a novel modified CD47 antibody (Hu5F9-IgG2σ). For the in vivo model, only samples refractory to CD19-DE monotherapy were chosen. Hu5F9-IgG2σ enhanced ADCP by CD19-DE in various BCP-ALL cell line models with varying CD19 surface expression and cytogenetic backgrounds, two of which contained the KMT2A-AFF1 fusion. Also, the antibody combination was efficient in inducing ADCP by human macrophages in pediatric PDX samples with and adult samples with and without KMT2A-rearrangement in vitro. In a randomized phase 2-like PDX trial using seven KMT2A-rearranged BCP-ALL samples in NSG mice, the CD19/CD47 antibody combination proved highly efficient. Our findings support that the efficacy of Fc-engineered CD19 antibodies may be substantially enhanced by a combination with CD47 blockade. This suggests that the combination may be a promising therapy option for BCP-ALL, especially in relapsed patients and/or patients refractory to CD19-directed therapy.

14.
J Funct Morphol Kinesiol ; 9(1)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38535420

RESUMO

Transcutaneous electrical nerve stimulation (TENS) has proven effective in treating pain in many experimental and clinical studies. In addition to the analgesic effect, direct TENS of peripheral nerves had anti-inflammatory and regenerative effects in the treatment of distal polyneuropathy and spinal cord injury. This work demonstrates the experience of using direct TENS in the treatment of a 52-year-old patient with post-COVID-19 Guillain-Barré (GBS) and acute transverse myelitis (ATM) overlap syndrome. Direct TENS of peripheral nerves showed high efficiency in enhancing the therapeutic effect of combined plasma exchange and pharmacotherapy by 89.5% with a significant reduction in neuropathic pain, motor and sensory deficits, bladder and bowel disorders and regression of neurophysiological changes. We suggest that direct TENS of peripheral nerves can be a promising option for combined therapy of GBS and ATM overlap syndrome and other diseases with the simultaneous development of distal polyneuropathy and spinal cord injury. Further trial studies are required.

15.
Rev Neurol (Paris) ; 180(4): 314-325, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38485630

RESUMO

Neurofeedback is a brain-computer interface tool enabling the user to self-regulate their neuronal activity, and ultimately, induce long-term brain plasticity, making it an interesting instrument to cure brain disorders. Although this method has been used successfully in the past as an adjunctive therapy in drug-resistant epilepsy, this approach remains under-explored and deserves more rigorous scientific inquiry. In this review, we present early neurofeedback protocols employed in epilepsy and provide a critical overview of the main clinical studies. We also describe the potential neurophysiological mechanisms through which neurofeedback may produce its therapeutic effects. Finally, we discuss how to innovate and standardize future neurofeedback clinical trials in epilepsy based on evidence from recent research studies.


Assuntos
Interfaces Cérebro-Computador , Epilepsia , Neurorretroalimentação , Humanos , Neurorretroalimentação/métodos , Epilepsia/terapia , Epilepsia/psicologia , Interfaces Cérebro-Computador/tendências , Plasticidade Neuronal/fisiologia , Autocontrole , Encéfalo/fisiologia , Encéfalo/fisiopatologia
16.
Cancer Lett ; 588: 216805, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38462035

RESUMO

Crosstalk between mast cells (MCs) and T lymphocytes (TLs) releases specific signals that create an environment conducive to tumor development. Conversely, they can protect against cancer by targeting tumor cells for destruction. Although their role in immunity and cancer is complex, their potential in anticancer strategies is often underestimated. When peripheral MCs are activated, they can affect cancer development. Tumor-infiltrating TLs may malfunction and contribute to aggressive cancer and poor prognoses. One promising approach for cancer patients is TL-based immunotherapies. Recent reports suggest that MCs modulate TL activity in solid tumors and may be a potential therapeutic layer in multitargeting anticancer strategies. Pharmacologically modulating MC activity can enhance the anticancer cytotoxic TL response in tumors. By identifying tumor-specific targets, it has been possible to genetically alter patients' cells into fully humanized anticancer cellular therapies for autologous transplantation, including the engineering of TLs and MCs to target and kill cancer cells. Hence, recent scientific evidence provides a broader understanding of MC-TL activity in cancer.


Assuntos
Neoplasias , Linfócitos T , Humanos , Linfócitos T/patologia , Mastócitos/patologia , Neoplasias/patologia , Linfócitos do Interstício Tumoral , Imunoterapia , Microambiente Tumoral
17.
Assessment ; : 10731911241237055, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515003

RESUMO

Given the popularity and ease of single-item craving assessments, we developed a multi-item measure and compared it to common single-item assessments in an ecological momentary assessment (EMA) context. Two weeks of EMA data were collected from 48 emerging adults (56.25% female, 85.42% White) who frequently used cannabis. Eight craving items were administered, and multilevel factor analyses were used to identify the best fitting model. The resulting scale's factors represented purposefulness/general desire and emotionality/negative affect craving. Convergent validity was examined using measures of craving, cannabis use disorder symptoms, frequency of use, cannabis cue reactivity, cannabis use, negative affect, and impulsivity. The scale factors were associated with cue-reactivity craving, negative affect, impulsivity, and subfactors of existing craving measures. For researchers interested in using a single item to capture craving, one item performed particularly well. However, the new scale may provide a more nuanced assessment of mechanisms underlying craving.

18.
Addiction ; 119(6): 1080-1089, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38403280

RESUMO

BACKGROUND AND AIMS: Non-alcoholic beverages (NABs) that mimic alcohol without inducing intoxication, such as non-alcoholic beers, non-alcoholic wines and spirit-free drinks, are increasing in popularity. It is unknown whether NABs help to mitigate or stimulate alcohol use. The present study aimed to describe NAB consumption practices among US adults consuming alcohol, characterize who is likely to consume NABs and examine whether NAB use influences desire for and perceived consumption of alcohol. DESIGN AND PARTICIPANTS: The survey study used data collected June-July 2023 from an on-line convenience sample. The first survey (n = 1906) assessed frequency of NAB consumption among US adults who consume alcohol. A second more detailed survey on use patterns was conducted with 466 respondents who reported past-year NAB consumption, of whom 153 (32.83%) screened positive on the CAGE questionnaire for alcohol use disorder (AUD). SETTING: This study took place in the United States. MEASUREMENTS: NAB consumption measures included type of NAB consumed, frequency, quantity, first consumption age, consumption reasons, consumption contexts and perceived effect on desire for and consumption of alcohol. Alcohol use measures included frequency, quantity and first consumption age. FINDINGS: Past-year NAB use was endorsed by 28.44% of respondents (61.70% ever used). Non-alcoholic liquor/'mocktails' were the most common NAB type consumed (83.69%). Compared with respondents without AUD, those who screened positive for AUD were significantly more likely to consume NABs in an effort to decrease or abstain from drinking alcohol [adjusted odds ratio (AOR) = 3.54, 95% confidence interval (CI) = 2.24-5.58] and 67.97% endorsed less alcohol consumption (3.23% endorsed more) due to their NAB use. NAB consumption frequency and quantity were significantly positively predicted by alcohol consumption frequency (AOR = 1.46, 95% CI = 1.17-1.83) and quantity (ß = 0.25, 95% CI = 0.15-0.35), respectively. CONCLUSION: Adults who consume alcohol and screen positive for alcohol use disorder report drinking non-alcoholic beverages as a harm reduction strategy.


Assuntos
Consumo de Bebidas Alcoólicas , Humanos , Masculino , Adulto , Feminino , Estados Unidos/epidemiologia , Consumo de Bebidas Alcoólicas/epidemiologia , Pessoa de Meia-Idade , Adulto Jovem , Inquéritos e Questionários , Adolescente , Bebidas , Idoso , Vinho
19.
Sci Rep ; 14(1): 846, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191600

RESUMO

Mycobacterium tuberculosis (Mtb) is able to transition into a dormant state, causing the latent state of tuberculosis. Dormant mycobacteria acquire resistance to all known antibacterial drugs and can survive in the human body for decades before becoming active. In the dormant forms of M. tuberculosis, the synthesis of porphyrins and its Zn-complexes significantly increased when 5-aminolevulinic acid (ALA) was added to the growth medium. Transcriptome analysis revealed an activation of 8 genes involved in the metabolism of tetrapyrroles during the Mtb transition into a dormant state, which may lead to the observed accumulation of free porphyrins. Dormant Mtb viability was reduced by more than 99.99% under illumination for 30 min (300 J/cm2) with 565 nm light that correspond for Zn-porphyrin and coproporphyrin absorptions. We did not observe any PDI effect in vitro using active bacteria grown without ALA. However, after accumulation of active cells in lung macrophages and their persistence within macrophages for several days in the presence of ALA, a significant sensitivity of active Mtb cells (ca. 99.99%) to light exposure was developed. These findings create a perspective for the treatment of latent and multidrug-resistant tuberculosis by the eradication of the pathogen in order to prevent recurrence of this disease.


Assuntos
Mycobacterium tuberculosis , Porfirinas , Tuberculose , Humanos , Ácido Aminolevulínico/farmacologia , Macrófagos , Zinco
20.
Dalton Trans ; 53(5): 2242-2251, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38193857

RESUMO

The magnetic and electronic structures of Fe4O5 have been investigated at ambient and high pressures via a combination of representation analysis, density functional theory (DFT+U) calculations, and Mössbauer spectroscopy. A few spin configurations corresponding to the different irreducible representations have been considered. The total-energy calculations reveal that the magnetic ground state of Fe4O5 corresponds to an orthogonal spin order. Depending on the magnetic propagation vector k, two spin-ordered phases with minimal energy differences are realized. The lowest energy magnetic phase is related to k = (0, 0, 0) and is characterized by ferromagnetic ordering of iron magnetic moments at prismatic sites along the b-axis and antiferromagnetic ordering of iron moments at octahedral sites along the c-axis. For the k = (1/2, 0, 0) phase, the moments in the prisms are antiferromagnetically ordered along the b-axis and the moments in the octahedra are still antiferromagnetically ordered along the c-axis. Under high pressure, Fe4O5 exhibits magnetic transitions with the corresponding electronic transitions of the metal-insulator type. At a critical pressure PC ∼ 60 GPa, the Fe ions at the octahedral sites undergo a high-spin to low-spin state crossover with a decrease in the unit-cell volume of ∼4%, while the Fe ions at the prismatic sites remain in the high-spin state up to 130 GPa. This site-dependent magnetic collapse is experimentally observed in the transformation of Mössbauer spectra measured at room temperature and high pressures.

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