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2.
Healthcare (Basel) ; 12(13)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38998827

RESUMEN

Cognitive restructuring (CR) aims to get people to challenge and modify their cognitive distortions, generating alternative, more adaptive thoughts. Behavioral, emotional, and physiological responses are modified by analyzing and changing dysfunctional thoughts. The person must have the cognitive capacity to participate in the analysis of their thoughts. CR for people with depression has positive effects, although there is little research on how it should be structured and applied. CR is a thought modification technique presented in the Nursing Interventions Classification (NIC), but is not organized in a sequential approach, and there is no procedure for applying it in practice. This scoping review aims to identify the structure, contents and assessment instruments used in CR for people with depressive symptoms and to analyze the health outcomes of applying the CR technique in this population. Out of 515 articles, seven studies were included in the review, up to 2021 and without any time limitation. The studies were not guided by a consistent and sound framework of the CR technique and each study used its own framework, although they used similar techniques. We grouped CR into six steps. No specific studies were found regarding intervention by nurses. CR is effective in reducing depressive symptoms, so it is an important therapeutic tool that should be used on people with depression. With this scoping review, mental health nurses will have a more comprehensive idea of the techniques that can be used in the application of CR to patients with depressive symptoms.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39059441

RESUMEN

OBJECTIVES: The aims of this study are to describe a computed tomographic (CT) measurement method of feline femoral, tibial, and patellar conformation, and to compare these measurements between a cat population diagnosed with medial patellar luxation (MPL) and cats without MPL. MATERIALS AND METHODS: Eleven measurements were performed by two observers, including anatomical lateral distal femoral angle (aLDFA), femoral trochlear width (FTW) and femoral trochlear depth (FTD), anteversion angle of the femoral neck, patellar length, patellar width, patellar height, patellar volume, mechanical medial proximal tibial angle, tibial torsion angle, and tibial tuberosity displacement. Mean and standard deviation differences between the groups were statistically assessed. Intraobserver and interobserver interclass correlation coefficients (ICCs) were calculated. RESULTS: The aLDFA was significantly higher in the MPL II compared with the control and MPL III. The FTW was significantly larger in the MPL III than in the control or the MPL II group. The FTD in the control group was significantly larger than in the MPL II and III groups. The TTA of the control group was significantly smaller than the MPL II and III. The intraobserver ICC was high at 64%, and the interobserver ICC was high at 36% of the measurements. CLINICAL SIGNIFICANCE: This study identified shallower FTD and increased TTA in cats diagnosed with MPL. The TTA difference was less than 5 degrees and FTD was less than 1 mm. The findings provide information on feline pelvic limb morphology. However, the differences between the two populations are small.

4.
Brain Spine ; 4: 102855, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39071452

RESUMEN

Introduction: Assessing the integrity of the posterior ligament complex (PLC), as a key element in the characterization of an unstable Thoracolumbar fracture (TLF), is challenging, but crucial in the choice of treatment. Research question: How to create a reproducible score using combined parameters of Computed Tomography (CT) to predict nonobvious PLC injury. How CT parameters relate with PLC status. Material and methods: Retrospective analysis of neurologically intact patients with an acute traumatic TLF, who underwent CT and Magnetic Resonance Imaging (MRI) within 72 h, in the Emergency Department of a single institution between January 2016 and 2022. Four investigators rated independently 11 parameters on CT and PLC integrity on MRI. The interrater reliability of the CT parameters was evaluated, and two risk scores were created to predict PLC injury on CT using the coefficients of the multivariate logistic regression. Results: 154 patients were included, of which 62 with PLC injury. All CT measurements had excellent or good interrater reliability. Patients with Horizontal Fracture of the lamina or pedicle (HLPF), Spinous process fracture (SPF) and Interspinous Distance Widening (IDW) were positively associated with PLC injury (p < 0.001, p < 0.001 and p = 0.045, respectively). Risk Score 2 (RS2), which included only statistically significant variables, had a total of 75.9% of correct classifications (p < 0.001), with a sensitivity of 71.0% and specificity of 78.3% to estimate PLC injury detected in the MRI. Discussion and conclusion: Standardized procedures pre-established in the CT measurement protocol were effective. Identically to early findings, those three CT measurements showed a positive relation to PLC injury, thus enhancing the conclusions of previous studies. Comparing to the reliability of the CT findings above mentioned, the score was less precise.

5.
bioRxiv ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38948777

RESUMEN

The protein alpha-synuclein (αSyn) plays a critical role in the pathogenesis of synucleinopathy, which includes Parkinson's disease and multiple system atrophy, and mounting evidence suggests that lipid dyshomeostasis is a critical phenotype in these neurodegenerative conditions. Previously, we identified that αSyn localizes to mitochondria-associated endoplasmic reticulum membranes (MAMs), temporary functional domains containing proteins that regulate lipid metabolism, including the de novo synthesis of phosphatidylserine. In the present study, we have analyzed the lipid composition of postmortem human samples, focusing on the substantia nigra pars compacta of Parkinson's disease and controls, as well as three less affected brain regions of Parkinson's donors. To further assess synucleinopathy-related lipidome alterations, similar analyses were performed on the striatum of multiple system atrophy cases. Our data show region-and disease-specific changes in the levels of lipid species. Specifically, our data revealed alterations in the levels of specific phosphatidylserine species in brain areas most affected in Parkinson's disease. Some of these alterations, albeit to a lesser degree, are also observed multiples system atrophy. Using induced pluripotent stem cell-derived neurons, we show that αSyn contributes to regulating phosphatidylserine metabolism at MAM domains, and that αSyn dosage parallels the perturbation in phosphatidylserine levels. Our results support the notion that αSyn pathophysiology is linked to the dysregulation of lipid homeostasis, which may contribute to the vulnerability of specific brain regions in synucleinopathy. These findings have significant therapeutic implications.

6.
Ir Vet J ; 77(1): 17, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39085947

RESUMEN

BACKGROUND: Surgery of the goat stifle joint requires good perioperative analgesia, ideally without affecting motor function in the postoperative period.  The objective of this study was to describe an ultrasound-guided technique for saphenous nerve block in goats. Eleven fresh female goat cadavers from two different age groups were used: seven of them were four years old with a mean ± SD body weight of 65.9 ± 7.3 kg. Four animals were six months old and their mean ± SD body weight was 20.1 ± 3.1 kg. The cadavers were positioned in lateral recumbency with the limb to be blocked lowermost. A high-frequency linear transducer (6-12 MHz) was used to localise the interfascial plane between the sartorius and the vastus medialis muscles and to identify the saphenous nerve on the medial aspect of the thigh, caudal to the femur, at the level of the femoral triangle. In 22 pelvic limbs 0.1 mL/kg of methylene blue was injected around the saphenous nerve under ultrasound guidance, followed by gross anatomical dissection. The length of circumferentially stained nerve was measured, and the success rate of achieving at least 1 cm of staining is presented with a 95% confidence interval (CI). RESULTS: Although not all saphenous nerves were sonographically identified, their boundaries were defined as cranial to the femoral artery, lateral to the sartorius muscle, and medial to the vastus medialis and rectus femoris muscles, within the perivascular fat. During anatomical dissection, the overall dye solution distribution was graded as complete in 17/22 limbs indicating a 77.3% success rate [95% CI (0.598, 0.948)], partial in 3/22 limbs and failed in 2/22 limbs. CONCLUSIONS: The success rate of this study indicates the feasibility of employing the ultrasound-guided technique to perform saphenous nerve block in goats. However, further in-vivo studies are recommended to assess the block's clinical efficacy before implementation on clinical patients.

7.
Sci Rep ; 14(1): 14067, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890330

RESUMEN

Prioritizing watershed management interventions relies on delineating homogeneous precipitation regions. In this study, we identify these regions in the Brazilian Legal Amazon based on the magnitude of Sen's Slope trends using annual precipitation data from September to August, employing the Google Earth Engine platform. Utilizing the silhouette method, we determine four distinct clusters representing zones of homogeneous precipitation patterns. Cluster 0 exhibits a significant median increase in precipitation of 3.20 mm year-1 over the period from 1981 to 2020. Cluster 1 shows a notable increase of 8.13 mm year-1, while Clusters 2 and 3 demonstrate reductions in precipitation of - 1.61 mm year-1 and - 3.87 mm year-1, respectively, all statistically significant. Notably, the region known as the arc of deforestation falls within Cluster 2, indicating a concerning trend of reduced precipitation. Additionally, our analysis reveals significant correlations between Sea Surface Temperature (SST) in various oceanic regions and precipitation patterns over the Brazilian Legal Amazon. Particularly noteworthy is the strong positive correlation with SST in the South Atlantic, while negative correlations are observed with SST in the South Pacific and North Atlantic. These findings provide valuable insights for enhancing climate adaptation strategies in the Brazilian Legal Amazon region.

8.
Viruses ; 16(6)2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38932240

RESUMEN

Human alphaherpesvirus 1 (HSV-1) is a significantly widespread viral pathogen causing recurrent infections that are currently incurable despite available treatment protocols. Studies have highlighted the potential of antimicrobial peptides sourced from Vespula lewisii venom, particularly those belonging to the mastoparan family, as effective against HSV-1. This study aimed to demonstrate the antiviral properties of mastoparans, including mastoparan-L [I5, R8], mastoparan-MO, and [I5, R8] mastoparan, against HSV-1. Initially, Vero cell viability was assessed in the presence of these peptides, followed by the determination of antiviral activity, mechanism of action, and dose-response curves through plaque assays. Structural analyses via circular dichroism and nuclear magnetic resonance were conducted, along with evaluating membrane fluidity changes induced by [I5, R8] mastoparan using fluorescence-labeled lipid vesicles. Cytotoxic assays revealed high cell viability (>80%) at concentrations of 200 µg/mL for mastoparan-L and mastoparan-MO and 50 µg/mL for [I5, R8] mastoparan. Mastoparan-MO and [I5, R8] mastoparan exhibited over 80% HSV-1 inhibition, with up to 99% viral replication inhibition, particularly in the early infection stages. Structural analysis indicated an α-helical structure for [I5, R8] mastoparan, suggesting effective viral particle disruption before cell attachment. Mastoparans present promising prospects for HSV-1 infection control, although further investigation into their mechanisms is warranted.


Asunto(s)
Antivirales , Herpesvirus Humano 1 , Péptidos y Proteínas de Señalización Intercelular , Péptidos , Venenos de Avispas , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 1/fisiología , Antivirales/farmacología , Antivirales/química , Animales , Células Vero , Chlorocebus aethiops , Péptidos/farmacología , Péptidos/química , Venenos de Avispas/farmacología , Venenos de Avispas/química , Péptidos y Proteínas de Señalización Intercelular/farmacología , Péptidos y Proteínas de Señalización Intercelular/química , Supervivencia Celular/efectos de los fármacos , Humanos , Replicación Viral/efectos de los fármacos
9.
World Neurosurg ; 188: e555-e560, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38823444

RESUMEN

BACKGROUND: Geniculocalcarine fibers are thought to be exclusively ipsilateral. However, recent findings challenged this belief, revealing bilateral recruiting responses in occipitotemporoparietal regions upon unilateral stimulation of the lateral geniculate nucleus (LGN) in humans. This raised the intriguing possibility of bilateral projections to primary visual areas (V1). This study sought to explore the hypothetical decussation of the geniculocalcarine tract. METHODS: 40 healthy individuals' 7T magnetic resonance images from the Human Connectome Project were examined. Employing MRtrix3 software with the constrained spherical deconvolution algorithm, scans were processed. LGN served as the seed region and contralateral regions of interest (splenium of the corpus callosum, posterior commissure, LGN, V1, pulvinar, and superior colliculus) were defined to reconstruct the hypothetical decussated fibers. Tractography included contralateral V1 as the target region in all segmentations, excluding ipsilateral V1 to eliminate fibers leading to or originating from this area. Additionally, a segmentation of the tract originating from LGN and projecting to the ipsilateral V1 was performed. Mean fraction anisotropy and mean diffusivity metrics were extracted from the density maps. RESULTS: Observations revealed a substantial volume of decussated fibers between LGN and contralateral V1 via the splenium of the corpus callosum, albeit much smaller than ipsilateral fibers. The volume of ipsilateral fibers was similar in both sides. Left LGN-originating decussated fibers were more than double those originating from the right LGN. Tract segmentation to other regions of interests yielded no fibers. CONCLUSIONS: This study suggests a partial decussation of the fibers between LGN and V1, likely constituting the geniculocalcarine tract.


Asunto(s)
Imagen de Difusión Tensora , Cuerpos Geniculados , Vías Visuales , Humanos , Cuerpos Geniculados/diagnóstico por imagen , Cuerpos Geniculados/anatomía & histología , Imagen de Difusión Tensora/métodos , Masculino , Femenino , Adulto , Vías Visuales/diagnóstico por imagen , Vías Visuales/anatomía & histología , Corteza Visual Primaria/diagnóstico por imagen , Corteza Visual Primaria/anatomía & histología , Conectoma/métodos , Adulto Joven , Imagen por Resonancia Magnética/métodos , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/anatomía & histología
11.
Belitung Nurs J ; 10(2): 143-151, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38690306

RESUMEN

Background: Musculoskeletal disorders (MSDs) pose a pervasive concern among nursing professionals due to the high physical workload. Simultaneously, the complex relationship between MSDs and mental health outcomes in this population remains an area of significant interest and importance. Objective: This study aimed to investigate the occurrence of MSDs and their relationships with burnout and psychological suffering within the nursing workforce. Methods: A cross-sectional study was conducted in 2020 involving 291 nursing professionals in Brazil. Standardized questionnaires were employed to gather information on MSDs, mental health outcomes, and pertinent work-related factors. Robust statistical analyses were conducted to ascertain the prevalence of MSDs, establish associations between MSDs and mental health outcomes, and delineate the influence of work-related factors on these associations. Statistical analysis was performed using the R software. Results: The study revealed a significant prevalence of musculoskeletal injuries (MSIs) among nursing workers, focusing on regions that include the lower back, upper back, neck, and shoulders. Individuals with MSIs in the lower back showed a marked increase in emotional exhaustion (p = 0.02), as did those with MSIs in the upper back (p <0.01) and depersonalization (p = 0.07). On the other hand, nursing professionals who reported MSIs in the neck and shoulders had considerably higher scores in emotional exhaustion (p <0.01 and p = 0.01, respectively) and depersonalization (p = 0.05 and p = 0.05, respectively). However, no significant correlations emerged between MSIs and depression or work-related factors. Conclusions: This study highlights the urgency of implementing proactive measures to prevent and manage MSDs within the nursing profession. Moreover, it emphasizes the critical need to enhance working conditions and provide robust support mechanisms to safeguard the mental health of nursing professionals.Open AccessOpen Access.

12.
Nat Immunol ; 25(7): 1207-1217, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38802512

RESUMEN

The contribution of γδ T cells to immune responses is associated with rapid secretion of interferon-γ (IFN-γ). Here, we show a perinatal thymic wave of innate IFN-γ-producing γδ T cells that express CD8αß heterodimers and expand in preclinical models of infection and cancer. Optimal CD8αß+ γδ T cell development is directed by low T cell receptor signaling and through provision of interleukin (IL)-4 and IL-7. This population is pathologically relevant as overactive, or constitutive, IL-7R-STAT5B signaling promotes a supraphysiological accumulation of CD8αß+ γδ T cells in the thymus and peripheral lymphoid organs in two mouse models of T cell neoplasia. Likewise, CD8αß+ γδ T cells define a distinct subset of human T cell acute lymphoblastic leukemia pediatric patients. This work characterizes the normal and malignant development of CD8αß+ γδ T cells that are enriched in early life and contribute to innate IFN-γ responses to infection and cancer.


Asunto(s)
Inmunidad Innata , Interferón gamma , Receptores de Antígenos de Linfocitos T gamma-delta , Receptores de Interleucina-7 , Factor de Transcripción STAT5 , Timo , Animales , Interferón gamma/metabolismo , Interferón gamma/inmunología , Ratones , Humanos , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Timo/inmunología , Receptores de Interleucina-7/metabolismo , Factor de Transcripción STAT5/metabolismo , Transducción de Señal/inmunología , Ratones Endogámicos C57BL , Linfocitos T CD8-positivos/inmunología , Ratones Noqueados , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Antígenos CD8/metabolismo , Femenino , Linfocitos Intraepiteliales/inmunología , Linfocitos Intraepiteliales/metabolismo , Interleucina-7/metabolismo
13.
Org Lett ; 26(19): 4065-4070, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38696591

RESUMEN

We introduce a novel and straightforward methodology for photoredox arylation of an indole scaffold using aryldiazonium salts under mild and metal-free conditions. Our approach enables the regioselective and chemoselective introduction of several aryl groups to the C(2) position of indoles and tryptophan, even in competition with other amino acids. This approach extends to the late-stage functionalization of peptides and lysozyme, heralding the unprecedented arylation of tryptophan residues in wild-type proteins and offering broad utility in chemical biology.


Asunto(s)
Indoles , Oxidación-Reducción , Triptófano , Triptófano/química , Indoles/química , Estructura Molecular , Procesos Fotoquímicos , Muramidasa/química , Péptidos/química , Estereoisomerismo , Catálisis
15.
Anal Bioanal Chem ; 416(13): 3239-3250, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38573343

RESUMEN

Cocaine and antidepressants rank high globally in substance consumption, emphasizing their impact on public health. The determination of these compounds and related substances in biological samples is crucial for forensic toxicology. This study focused on developing an innovative analytical method for the determination of cocaine, antidepressants, and their related metabolites in postmortem blood samples, using unmodified commercial Fe3O4 nanoparticles as a sorbent for dispersive magnetic solid-phase extraction (m-d-SPE), coupled with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. An aliquot of 100 µL of whole blood and 5 µL of the internal standard pool were added to 30 mg of nanoparticles. The nanoparticles were separated from the sample using a neodymium magnet inserted into a 3D-printed microtube rack. The liquid was then discarded, followed by desorption with 300 µL of 1/1/1 acetonitrile/methanol/ethyl acetate. The sample was vortexed and separated, and 1.5 µL of the organic supernatant was injected into the LC-MS/MS. The method was acceptably validated and successfully applied to 263 postmortem blood samples. All samples evaluated in this study were positive for at least one substance. The most frequent analyte was benzoylecgonine, followed by cocaine and cocaethylene. The most common antidepressants encountered in the analyzed samples were citalopram and fluoxetine, followed by fluoxetine's metabolite norfluoxetine. This study describes the first report of this sorbent in postmortem blood analysis, demonstrating satisfactory results for linearity, precision, accuracy, and selectivity for all compounds. The method's applicability was confirmed, establishing it as an efficient and sustainable alternative to traditional techniques for forensic casework.


Asunto(s)
Antidepresivos , Cocaína , Toxicología Forense , Nanopartículas de Magnetita , Extracción en Fase Sólida , Espectrometría de Masas en Tándem , Humanos , Cocaína/sangre , Cocaína/análogos & derivados , Antidepresivos/sangre , Espectrometría de Masas en Tándem/métodos , Toxicología Forense/métodos , Extracción en Fase Sólida/métodos , Nanopartículas de Magnetita/química , Cromatografía Liquida/métodos , Límite de Detección , Detección de Abuso de Sustancias/métodos , Masculino , Femenino , Adulto
16.
Adv Healthc Mater ; 13(18): e2303765, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38651610

RESUMEN

Despite progress in bone tissue engineering, reconstruction of large bone defects remains an important clinical challenge. Here, a biomaterial designed to recruit bone cells, endothelial cells, and neuronal fibers within the same matrix is developed, enabling bone tissue regeneration. The bioactive matrix is based on modified elastin-like polypeptides (ELPs) grafted with laminin-derived adhesion peptides IKVAV and YIGSR, and the SNA15 peptide for retention of hydroxyapatite (HA) particles. The composite matrix shows suitable porosity, interconnectivity, biocompatibility for endothelial cells, and the ability to support neurites outgrowth by sensory neurons. Subcutaneous implantation leads to the formation of osteoid tissue, characterized by the presence of bone cells, vascular networks, and neuronal structures, while minimizing inflammation. Using a rat femoral condyle defect model, longitudinal micro-CT analysis is performed, which demonstrates a significant increase in the volume of mineralized tissue when using the ELP-based matrix compared to empty defects and a commercially available control (Collapat). Furthermore, visible blood vessel networks and nerve fibers are observed within the lesions after a period of two weeks. By incorporating multiple key components that support cell growth, mineralization, and tissue integration, this ELP-based composite matrix provides a holistic and versatile solution to enhance bone tissue regeneration.


Asunto(s)
Regeneración Ósea , Elastina , Ingeniería de Tejidos , Animales , Elastina/química , Ratas , Ingeniería de Tejidos/métodos , Regeneración Ósea/efectos de los fármacos , Humanos , Andamios del Tejido/química , Durapatita/química , Durapatita/farmacología , Huesos , Ratas Sprague-Dawley , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Microtomografía por Rayos X
17.
Ann Hepatol ; 29(4): 101497, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38460715

RESUMEN

INTRODUCTION AND OBJECTIVES: Autoimmune hepatitis (AIH) is a rare disease with a complex and not fully understood pathogenesis. Prognostic factors that might influence treatment response, relapse rates, and transplant-free survival are not well established. This study investigates clinical and biochemical markers associated with response to immunosuppression in patients with AIH. MATERIALS AND METHODS: This retrospective cohort study included 102 patients with AIH treated with immunosuppressants and followed at the Federal University of Minas Gerais, Brazil, from 1990 to 2018. Pretreatment data such as clinical profiles, laboratory, and histological exams were analyzed regarding biochemical response at one year, histological remission, relapse, and death/transplantation rates. RESULTS: Cirrhosis was present in 59 % of cases at diagnosis. One-year biochemical remission was observed in 55.7 % of the patients and was found to be a protective factor for liver transplant. Overall survival was 89 %. Patients with ascites at disease onset showed a higher aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ratio and elevated Model of end-stage liver disease (MELD) score. The presence of ascites was significantly associated with a 20-fold increase in mortality rate. CONCLUSIONS: AIH has a severe clinical phenotype in Brazilians, with high rates of cirrhosis and low remission rates. Early diagnosis and treatment are essential for achieving remission and reducing complications. The presence of ascites is significantly associated with mortality, emphasizing the importance of monitoring and prompt intervention. This study also stresses the need for further research on AIH in Latin America.


Asunto(s)
Hepatitis Autoinmune , Inmunosupresores , Humanos , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/mortalidad , Hepatitis Autoinmune/patología , Masculino , Femenino , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Inmunosupresores/uso terapéutico , Pronóstico , Brasil/epidemiología , Resultado del Tratamiento , Trasplante de Hígado , Cirrosis Hepática/mortalidad , Recurrencia , Aspartato Aminotransferasas/sangre , Alanina Transaminasa/sangre , Inducción de Remisión , Biomarcadores/sangre , Adulto Joven , Ascitis/etiología , Anciano
18.
Drug Test Anal ; 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38440942

RESUMEN

Driving under the influence of cannabis (DUIC) is increasing worldwide, and cannabis is the most prevalent drug after alcohol in impaired driving cases, emphasizing the need for a reliable traffic enforcement strategy. ∆9 -tetrahydrocannabinol (THC) detection in oral fluid has great potential for identifying recent cannabis use; however, additional data are needed on the sensitivities, specificities, and efficiencies of different oral fluid devices for detecting cannabinoids at the roadside by police during routine traffic safety enforcement efforts. At the roadside, 8945 oral fluid THC screening tests were performed with four devices: AquilaScan®, Dräger DrugTest®, WipeAlyser Reader®, and Druglizer®. A total of 530 samples screened positive for THC (5.9%) and were analyzed by liquid chromatography-tandem mass spectrometry at multiple cutoff concentrations (2 ng/mL, 10 ng/mL, and manufacturers' recommended device cutoffs) to investigate device performance. Results varied substantially, with sensitivities of 0%-96.8%, specificities of 89.8%-98.5%, and efficiencies of 84.3%-97.8%. The Dräger DrugTest® outperformed the other devices with a 96.8% sensitivity, 97.1% specificity, and 97.0% efficiency at a 5-ng/mL LC-MS/MS confirmation cutoff. The WipeAlyser Reader® had good performance with a 91.4% sensitivity, 97.2% specificity, and 96.4% efficiency. AquilaScan® and Druglizer® had unacceptable performance for cannabinoid detection, highlighted by sensitivity <13%. The choice of roadside oral fluid testing device must offer good analytical performance for cannabinoids because of its high prevalence of use and impact on road safety.

19.
Blood ; 143(15): 1488-1495, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38437507

RESUMEN

ABSTRACT: Relapsed or refractory acute myeloid leukemia (AML) remains a major therapeutic challenge. We have recently developed a Vδ1+ γδ T cell-based product for adoptive immunotherapy, named Delta One T (DOT) cells, and demonstrated their cytolytic capacity to eliminate AML cell lines and primary blasts in vitro and in vivo. However, the molecular mechanisms responsible for the broad DOT-cell recognition of AML cells remain poorly understood. Here, we dissected the role of natural killer (NK) cell receptor ligands in AML cell recognition by DOT cells. Screening of multiple AML cell lines highlighted a strong upregulation of the DNAM-1 ligands, CD155/pulmonary vascular resistance (PVR), CD112/nectin-2, as well as the NKp30 ligand, B7-H6, in contrast with NKG2D ligands. CRISPR-mediated ablation revealed key nonredundant and synergistic contributions of PVR and B7-H6 but not nectin-2 to DOT-cell targeting of AML cells. We further demonstrate that PVR and B7-H6 are critical for the formation of robust immunological synapses between AML and DOT cells. Importantly, PVR but not B7-H6 expression in primary AML samples predicted their elimination by DOT cells. These data provide new mechanistic insight into tumor targeting by DOT cells and suggest that assessing PVR expression levels may be highly relevant to DOT cell-based clinical trials.


Asunto(s)
Citotoxicidad Inmunológica , Leucemia Mieloide Aguda , Humanos , Células Asesinas Naturales , Linfocitos T , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Línea Celular
20.
J Anal Toxicol ; 48(5): 314-331, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38334744

RESUMEN

Urine toxicological analysis is a relevant tool in both clinical and forensic scenarios, enabling the diagnosis of acute poisonings, elucidation of deaths, verification of substance use in the workplace and identification of drug-facilitated crimes. For these analyses, the dilute-and-shoot technique associated with liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) is a promising alternative since it has demonstrated satisfactory results and broad applicability. This study developed and validated a comprehensive LC-MS-MS screening method to analyze 95 illicit drugs and medicines in urine samples and application to clinical and forensic Brazilian cases. The dilute-and-shoot protocol was defined through multivariate optimization studies and was set using 100 µL of sample and 300 µL of solvent. The total chromatographic run time was 7.5 min. The method was validated following the recommendations of the ANSI/ASB Standard 036 Guideline. The lower limits of quantification varied from 20 to 100 ng/mL. Within-run and between-run precision coefficient of variations% were <20%, and bias was within ± 20%. Only 4 of the 95 analytes presented significant ionization suppression or enhancement (>25%). As proof of applicability, 839 urine samples from in vivo and postmortem cases were analyzed. In total, 90.9% of the analyzed samples were positive for at least one substance, and 78 of the 95 analytes were detected. The most prevalent substances were lidocaine (40.2%), acetaminophen (38.0%) and benzoylecgonine (31.5%). The developed method proved to be an efficient and simplified alternative for analyzing 95 therapeutic and illicit drugs in urine samples. Additionally, the results obtained from sample analysis are essential for understanding the profile of Brazilian substance use, serving as a valuable database for the promotion of health and safety public policies.


Asunto(s)
Toxicología Forense , Drogas Ilícitas , Detección de Abuso de Sustancias , Espectrometría de Masas en Tándem , Humanos , Drogas Ilícitas/orina , Brasil , Detección de Abuso de Sustancias/métodos , Cromatografía Liquida , Toxicología Forense/métodos , Reproducibilidad de los Resultados , Límite de Detección , Cromatografía Líquida con Espectrometría de Masas
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