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BACKGROUND: Bacteria-based cancer therapy have demonstrated innovative strategies to combat tumors. Recent studies have focused on gram-negative bacterial outer membrane vesicles (OMVs) as a novel cancer immunotherapy strategy due to its intrinsic properties as a versatile carrier. METHOD: Here, we developed an Human Papillomavirus (HPV)-associated E7 antigen displaying Salmonella-derived OMV vaccine, utilizing a Poly(L-arginine) cell penetrating peptide (CPP) to enhance HPV16 E7 (aa49-67) H-2 Db and OMV affinity, termed SOMV-9RE7. RESULTS: Due to OMV's intrinsic immunogenic properties, SOMV-9RE7 effectively activates adaptive immunity through antigen-presenting cell uptake and antigen cross-presentation. Vaccination of engineered OMVs shows immediate tumor suppression and recruitment of infiltrating tumor-reactive immune cells. CONCLUSION: The simplicity of the arginine coating strategy boasts the versatility of immuno-stimulating OMVs that can be broadly implemented to personalized bacterial immunotherapeutic applications.
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Arginina , Vacunas contra el Cáncer , Proteínas E7 de Papillomavirus , Proteínas E7 de Papillomavirus/inmunología , Vacunas contra el Cáncer/inmunología , Humanos , Animales , Membrana Externa Bacteriana/inmunología , Ratones Endogámicos C57BL , FemeninoRESUMEN
In this study, we examined the risk of sexually transmitted infections (STIs) among adolescents and young adults (AYAs) with borderline personality disorder (BPD). A total of 4649 AYAs with BPD and 46,490 age-, sex-, and socioeconomic-matched controls without BPD were enrolled from the National Health Insurance Research Database of Taiwan from 2001 to 2009 and were followed up until the end of 2011. Participants who contracted any STI during the follow-up period were identified. Cox regression analysis was conducted to examine the risk of contracting any STI among both patients and controls. A total of 4649 AYAs with BPD and 46,490 age-, sex-, and socioeconomic-matched controls without BPD were enrolled from the National Health Insurance Research Database of Taiwan from 2001 to 2009 and were followed up until the end of 2011. Participants who contracted any STI (ICD-9-CM code 042, 091-097, 087.11, 078.8, 078.88, 131, and 054.1) during the follow-up period were identified. Cox regression and sub-analyses stratified by sex, age, psychiatric comorbidity subgroups, and psychotropic medication usage were conducted to assess STI risk. AYAs with BPD were at a higher risk of contracting any STI (hazard ratio [HR] = 50.79, 95% confidence interval [CI] = 33.45-77.11) in comparison with controls, including HIV, syphilis, genital warts, gonorrhea, chlamydia, trichomoniasis, and genital herpes. The association of BPD with an increased risk of any STI was prevalent in both sexes, adolescents, and young adult patients. BPD with or without psychiatric comorbid subgroup were all associated with an elevated risk of contracting any STI relative to the control group. AYAs with BPD are highly susceptible to contracting STIs. Future studies should examine the role of the core symptoms of BPD, sexual orientation, risky sex behaviors, depressive and anxiety symptoms, and substance use before sex in the risk of STIs among AYAs with BPD.
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Some bispecific radiotracers have been developed to overcome the limitations of monospecific tracers and improve detection sensitivity for heterogeneous tumor lesions. Here, we aim to synthesize two bispecific tracers targeting prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP), which are key markers expressed in prostate cancer. A pyridine-based FAP-targeted ligand was synthesized through multi-step organic synthesis and then connected to the 2-Nal-containing PSMA-targeted motif. The Ki(PSMA) values of Ga-complexed bispecific ligands, Ga-AV01084 and Ga-AV01088, were 11.6 ± 3.25 and 28.7 ± 6.05 nM, respectively, and the IC50(FAP) values of Ga-AV01084 and Ga-AV01088 were 10.9 ± 0.67 and 16.7 ± 1.53 nM, respectively. Both [68Ga]Ga-AV01084 and [68Ga]Ga-AV01088 enabled the visualization of PSMA-expressing LNCaP tumor xenografts and FAP-expressing HEK293T:hFAP tumor xenografts in PET images acquired at 1 h post-injection. However, the tumor uptake values from the bispecific tracers were still lower than those obtained from the monospecific tracers, PSMA-targeted [68Ga]Ga-PSMA-617 and FAP-targeted [68Ga]Ga-AV02070. Further investigations are needed to optimize the selection of linkers and targeted pharmacophores to improve the tumor uptake of bispecific PSMA/FAP tracers for prostate cancer imaging.
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Radioisótopos de Galio , Neoplasias de la Próstata , Masculino , Humanos , Células HEK293 , Farmacóforo , Radiofármacos/metabolismo , Neoplasias de la Próstata/patología , Piridinas , Tomografía de Emisión de Positrones , Línea Celular TumoralRESUMEN
Gastrin-releasing peptide receptor (GRPR), overexpressed in many solid tumors, is a promising imaging marker and therapeutic target. Most reported GRPR-targeted radioligands contain a C-terminal amide. Based on the reported potent antagonist D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH, we synthesized C-terminal hydroxamate-derived [68Ga]Ga-LW02075 ([68Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH) and [68Ga]Ga-LW02050 ([68Ga]Ga-DOTA-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH), and compared them with the closely related and clinically validated [68Ga]Ga-SB3 ([68Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt). Binding affinities (Ki) of Ga-SB3, Ga-LW02075, and Ga-LW02050 were 1.20 ± 0.31, 1.39 ± 0.54, and 8.53 ± 1.52 nM, respectively. Both Ga-LW02075 and Ga-LW02050 were confirmed to be GRPR antagonists by calcium release assay. Imaging studies showed that PC-3 prostate cancer tumor xenografts were clearly visualized at 1 h post injection by [68Ga]Ga-SB3 and [68Ga]Ga-LW02050 in PET images, but not by [68Ga]Ga-LW02075. Ex vivo biodistribution studies conducted at 1 h post injection showed that the tumor uptake of [68Ga]Ga-LW02050 was comparable to that of [68Ga]Ga-SB3 (5.38 ± 1.00 vs. 6.98 ± 1.36 %ID/g), followed by [68Ga]Ga-LW02075 (3.97 ± 1.71 %ID/g). [68Ga]Ga-SB3 had the highest pancreas uptake (37.3 ± 6.90 %ID/g) followed by [68Ga]Ga-LW02075 (17.8 ± 5.24 %ID/g), while the pancreas uptake of [68Ga]Ga-LW02050 was only 0.53 ± 0.11 %ID/g. Our data suggest that [68Ga]Ga-LW02050 is a promising PET tracer for detecting GRPR-expressing cancer lesions.
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Radioisótopos de Galio , Ácidos Hidroxámicos , Tomografía de Emisión de Positrones , Radiofármacos , Receptores de Bombesina , Receptores de Bombesina/metabolismo , Receptores de Bombesina/antagonistas & inhibidores , Radioisótopos de Galio/química , Animales , Humanos , Tomografía de Emisión de Positrones/métodos , Ratones , Ácidos Hidroxámicos/química , Ácidos Hidroxámicos/farmacocinética , Ácidos Hidroxámicos/síntesis química , Radiofármacos/química , Radiofármacos/síntesis química , Radiofármacos/farmacocinética , Línea Celular Tumoral , Distribución Tisular , Masculino , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismoRESUMEN
Selective manipulation of neural circuits using optogenetics and chemogenetics holds great translational potential but requires genetic access to neurons. Here, we demonstrate a general framework for identifying genetic tool-independent, pharmacological strategies for neural circuit-selective modulation. We developed an economically accessible calcium imaging-based approach for large-scale pharmacological scans of endogenous receptor-mediated neural activity. As a testbed for this approach, we used the mouse locus coeruleus due to the combination of its widespread, modular efferent neural circuitry and its wide variety of endogenously expressed GPCRs. Using machine learning-based action potential deconvolution and retrograde tracing, we identified an agonist cocktail that selectively inhibits medial prefrontal cortex-projecting locus coeruleus neurons. In vivo, this cocktail produces synergistic antinociception, consistent with selective pharmacological blunting of this neural circuit. This framework has broad utility for selective targeting of other neural circuits under different physiological and pathological states, facilitating non-genetic translational applications arising from cell type-selective discoveries.
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Tissue-resident memory T cells (TRM) are a specialized T cell population residing in peripheral tissues. The presence and potential impact of TRM in the tumor immune microenvironment (TIME) remain to be elucidated. Here, we systematically investigated the relationship between TRM and melanoma TIME based on multiple clinical single-cell RNA-seq datasets and developed signatures indicative of TRM infiltration. TRM infiltration is associated with longer overall survival and abundance of T cells, NK cells, M1 macrophages, and memory B cells in the TIME. A 22-gene TRM-derived risk score was further developed to effectively classify patients into low- and high-risk categories, distinguishing overall survival and immune activation, particularly in T cell-mediated responses. Altogether, our analysis suggests that TRM abundance is associated with melanoma TIME activation and patient survival, and the TRM-based machine learning model can potentially predict prognosis in melanoma patients.
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Cancer immunotherapy represents a paradigm shift in oncology, offering a superior anti-tumor efficacy and the potential for durable remission. The success of personalized vaccines and cell therapies hinges on the identification of immunogenic epitopes capable of eliciting an effective immune response. Current limitations in the availability of immunogenic epitopes restrict the broader application of such therapies. A critical criterion for serving as potential cancer antigens is their ability to stably bind to the major histocompatibility complex (MHC) for presentation on the surface of tumor cells. To address this, we have developed a comprehensive database of MHC epitopes, experimentally validated for their MHC binding and cell surface presentation. Our database catalogs 451 065 MHC peptide epitopes, each with experimental evidence for MHC binding, along with detailed information on human leukocyte antigen allele specificity, source peptides, and references to original studies. We also provide the grand average of hydropathy scores and predicted immunogenicity for the epitopes. The database (MHCepitopes) has been made available on the web and can be accessed at https://github.com/jcm1201/MHCepitopes.git. By consolidating empirical data from various sources coupled with calculated immunogenicity and hydropathy values, our database offers a robust resource for selecting actionable tumor antigens and advancing the design of antigen-specific cancer immunotherapies. It streamlines the process of identifying promising immunotherapeutic targets, potentially expediting the development of effective antigen-based cancer immunotherapies.
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Tissue-resident memory T cells (TRM) are a specialized subset of long-lived memory T cells that reside in peripheral tissues. However, the impact of TRM-related immunosurveillance on the tumor-immune microenvironment (TIME) and tumor progression across various non-small-cell lung cancer (NSCLC) patient populations is yet to be elucidated. Our comprehensive analysis of multiple independent single-cell and bulk RNA-seq datasets of patient NSCLC samples generated reliable, unique TRM signatures, through which we inferred the abundance of TRM in NSCLC. We discovered that TRM abundance is consistently positively correlated with CD4+ T helper 1 cells, M1 macrophages, and resting dendritic cells in the TIME. In addition, TRM signatures are strongly associated with immune checkpoint and stimulatory genes and the prognosis of NSCLC patients. A TRM-based machine learning model to predict patient survival was validated and an 18-gene risk score was further developed to effectively stratify patients into low-risk and high-risk categories, wherein patients with high-risk scores had significantly lower overall survival than patients with low-risk. The prognostic value of the risk score was independently validated by the Cancer Genome Atlas Program (TCGA) dataset and multiple independent NSCLC patient datasets. Notably, low-risk NSCLC patients with higher TRM infiltration exhibited enhanced T-cell immunity, nature killer cell activation, and other TIME immune responses related pathways, indicating a more active immune profile benefitting from immunotherapy. However, the TRM signature revealed low TRM abundance and a lack of prognostic association among lung squamous cell carcinoma patients in contrast to adenocarcinoma, indicating that the two NSCLC subtypes are driven by distinct TIMEs. Altogether, this study provides valuable insights into the complex interactions between TRM and TIME and their impact on NSCLC patient prognosis. The development of a simplified 18-gene risk score provides a practical prognostic marker for risk stratification.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Células T de Memoria , Microambiente Tumoral , Humanos , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/genética , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Pronóstico , Células T de Memoria/inmunología , Memoria Inmunológica , Linfocitos Infiltrantes de Tumor/inmunologíaRESUMEN
Bacteria-based cancer therapy employs various strategies to combat tumors, one of which is delivering tumor-associated antigen (TAA) to generate specific immunity. Here, we utilized a poly-arginine extended HPV E7 antigen (9RE7) for attachment on Salmonella SL7207 outer membrane to synthesize the bacterial vaccine Salmonella-9RE7 (Sal-9RE7), which yielded a significant improvement in the amount of antigen presentation compared to the previous lysine-extended antigen coating strategy. In TC-1 tumor mouse models, Sal-9RE7 monotherapy decreased tumor growth by inducing E7 antigen-specific immunity. In addition, pairing Sal-9RE7 with adjuvant Albumin-IFNß (Alb-IFNß), a protein cytokine fusion, the combination significantly increased the antitumor efficacy and enhanced immunogenicity in the tumor microenvironment (TME). Our study made a significant contribution to personalized bacterial immunotherapy via TAA delivery and demonstrated the advantage of combination therapy.
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Interferón Tipo I , Neoplasias , Animales , Ratones , Proteínas E7 de Papillomavirus/genética , Linfocitos T CD8-positivos , Neoplasias/terapia , Antígenos de Neoplasias , Inmunoterapia , Salmonella , Microambiente TumoralRESUMEN
BACKGROUND: Overexpressed in various solid tumors, gastrin-releasing peptide receptor (GRPR) is a promising cancer imaging marker and therapeutic target. Although antagonists are preferable for the development of GRPR-targeted radiopharmaceuticals due to potentially fewer side effects, internalization of agonists may lead to longer tumor retention and better treatment efficacy. In this study, we systematically investigated unnatural amino acid substitutions to improve in vivo stability and tumor uptake of a previously reported GRPR-targeted agonist tracer, [68Ga]Ga-TacBOMB2 (68Ga-DOTA-Pip-D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13-Thz14-NH2). RESULTS: Unnatural amino acid substitutions were conducted for Gln7, Trp8, Ala9, Val10, Gly11 and His12, either alone or in combination. Out of 25 unnatural amino acid substitutions, tert-Leu10 (Tle10) and NMe-His12 substitutions were identified to be preferable modifications especially in combination. Compared with the previously reported [68Ga]Ga-TacBOMB2, the Tle10 and NMe-His12 derived [68Ga]Ga-LW01110 showed retained agonist characteristics and improved GRPR binding affinity (Ki = 7.62 vs 1.39 nM), in vivo stability (12.7 vs 89.0% intact tracer in mouse plasma at 15 min post-injection) and tumor uptake (5.95 vs 16.6 %ID/g at 1 h post-injection). CONCLUSIONS: Unnatural amino acid substitution is an effective strategy to improve in vivo stability and tumor uptake of peptide-based radiopharmaceuticals. With excellent tumor uptake and tumor-to-background contrast, [68Ga]Ga-LW01110 is promising for detecting GRPR-expressing cancer lesions with PET. Since agonists can lead to internalization upon binding to receptors and foreseeable long tumor retention, our optimized GRPR-targeted sequence, [Tle10,NMe-His12,Thz14]Bombesin(7-14), is a promising template for use for the design of GRPR-targeted radiotherapeutic agents.
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Gastrin-releasing peptide receptor (GRPR) is overexpressed in various cancers and is a promising target for cancer diagnosis and therapy. However, the high pancreas uptake and/or metabolic instability observed for most reported GRPR-targeted radioligands might limit their clinical applications. Our group recently reported a GRPR-targeted antagonist tracer, [68Ga]Ga-TacsBOMB2 ([68Ga]Ga-DOTA-Pip-D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13ψThz14-NH2), which showed a minimal pancreas uptake in a preclinical mouse model. In this study, we synthesized four derivatives with unnatural amino acid substitutions (Tle10-derived Ga-LW01158, NMe-His12-derived Ga-LW01160, α-Me-Trp8- and Tle10-derived Ga-LW01186, and Tle10- and N-Me-Gly11-derived Ga-LW02002) and evaluated their potential for detecting GRPR-expressing tumors with positron emission tomography (PET). The binding affinities (Ki(GRPR)) of Ga-LW01158, Ga-LW01160, Ga-LW01186, and Ga-LW02002 were 5.11 ± 0.47, 187 ± 17.8, 6.94 ± 0.95, and 11.0 ± 0.39 nM, respectively. [68Ga]Ga-LW01158, [68Ga]Ga-LW01186, and [68Ga]Ga-LW02002 enabled clear visualization of subcutaneously implanted human prostate cancer PC-3 tumor xenografts in mice in PET images. Ex vivo biodistribution studies showed that [68Ga]Ga-LW01158 had the highest tumor uptake (11.2 ± 0.65 %ID/g) and good tumor-to-background uptake ratios at 1 h post-injection. Comparable in vivo stabilities were observed for [68Ga]Ga-LW01158, [68Ga]Ga-LW01186, and [68Ga]Ga-LW02002 (76.5-80.7% remaining intact in mouse plasma at 15 min post-injection). In summary, the Tle10 substitution, either alone or combined with α-Me-Trp8 or NMe-Gly11 substitution, in Ga-TacsBOMB2 generates derivatives that retained good GRPR binding affinity and in vivo stability. With good tumor uptake and tumor-to-background imaging contrast, [68Ga]Ga-LW01158 is promising for detecting GRPR-expressing lesions with PET.
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AIMS: Low-energy shock waves (LESWs) are known to alter cell-membrane permeability. This study aimed to investigate the effect of LESWs on Escherichia coli and E. coli-induced cystitis in rats. MAIN METHODS: Standardized suspensions of E. coli ATCC25922 were treated with or without LESWs (100 or 300 pulses; 0.12 mJ/mm2; 2 pulses/s) followed by bacterial counting, an antibiotic sensitivity test, and gene ontology analysis and gene-set enrichment analysis. Intravesical administration of saline or E. coli (0.5 mL with 108 CFU/mL) for 30 min was performed in female Sprague-Dawley rats. The rats were treated with or without LESWs (300 pulses; 0.12 mJ/mm2; 2 pulses/s) on days 4 and 5. The changes in inflammatory reactions, uroplakin IIIa staining, and correlation with urodynamic findings were assessed on day 8. KEY FINDINGS: LESW treatment induced a decrease in CFU and the autoaggregation rate and increased the inhibition zone sizes in a cefazolin-sensitivity study. These changes were associated with gene expression in regulation of cellular membrane components, biofilm formation, and the ATP-binding cassette transporter pathway. E. coli induced bladder hyperactivity and an inflammatory reaction as well as decreased uroplakin IIIa staining; these effects were partially reversed by LESW treatment. SIGNIFICANCE: The LESW antibacterial effect occurs by altering bacterial cell-membrane gene expression, enhancing antibiotic sensitivity, and inhibiting bladder inflammatory reaction and overactivity. These findings support the potential benefits of LESWs for treatment of recurrent or refractory bacterial cystitis.
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Fibroblast activation protein-α (FAP) is a marker of cancer-associated fibroblasts (CAFs) that constitute a significant portion of most carcinomas. Since it plays a critical role in tumor growth and metastasis, its timely detection to identify tumor lesions in early developmental stages using targeted radiopharmaceuticals has gained significant impetus. In the present work, two novel FAP-targeted precursors SB03178 and SB04033 comprising of an atypical benzo[h]quinoline construct were synthesized and either chelated to diagnostic radionuclide gallium-68 or therapeutic radionuclide lutetium-177, with ≥90% radiochemical purities and 22-76% decay-corrected radiochemical yields. natGa-labeled complexes displayed dose-dependent FAP inhibition, with binding potency of natGa-SB03178 being â¼17 times higher than natGa-SB04033. To evaluate their pharmacokinetic profiles, PET imaging and ex vivo biodistribution analyses were executed in FAP-overexpressing HEK293T:hFAP tumor-bearing mice. While both tracers displayed clear tumor visualization that was primarily FAP-arbitrated, with negligible uptake in most peripheral tissues, [68Ga]Ga-SB03178 demonstrated higher tumor uptake and superior tumor-to-background contrast ratios than [68Ga]Ga-SB04033. 177Lu-labeled SB03178 was subjected to tumor retention studies, mouse dosimetry profiling and mouse-to-human dose extrapolations also using the HEK293T:hFAP tumor model. [177Lu]Lu-SB03178 exhibited a combination of high and sustained tumor uptake, with excellent tumor-to-critical organ uptake ratios resulting in a high radiation absorbed dose to the tumor and a low estimated whole-body dose to humans. Our preliminary findings are considerably encouraging to support clinical development of [68Ga]Ga-/[177Lu]Lu-SB03178 theranostic pair for use in a vast majority of FAP-overexpressing neoplasms, particularly carcinomas.
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Carcinoma , Endopeptidasas , Proteínas de la Membrana , Quinolinas , Humanos , Animales , Ratones , Radioisótopos de Galio , Distribución Tisular , Células HEK293 , Radioisótopos , Radiofármacos/farmacocinética , Quinolinas/química , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Línea Celular TumoralRESUMEN
Cartilage damage, a common cause of osteoarthritis, requires medical imaging for accurate diagnosis of pathological changes. However, current instruments can acquire limited imaging information due to sensitivity and resolution issues. Therefore, multimodal imaging is considered an alternative strategy to provide valuable images and analyzes from different perspectives. Among all biomaterials, gold nanomaterials not only exhibit outstanding benefits as drug carriers, in vitro diagnostics, and radiosensitizers, but are also widely used as contrast agents, particularly for tumors. However, their potential for imaging cartilage damage is rarely discussed. In this study, we developed a versatile iodinated gadolinium-gold nanomaterial, AuNC@BSA-Gd-I, and its radiolabeled derivative, AuNC@BSA-Gd-131I, for cartilage detection. With its small size, negative charge, and multimodal capacities, the probe can penetrate damaged cartilage and be detected or visualized by computed tomography, MRI, IVIS, and gamma counter. Additionally, the multimodal imaging potential of AuNC@BSA-Gd-I was compared to current multifunctional gold nanomaterials containing similar components, including anionic AuNC@BSA, AuNC@BSA-I, and AuNC@BSA-Gd as well as cationic AuNC@CBSA. Due to their high atomic numbers and fluorescent emission, AuNC@BSA nanomaterials could provide fundamental multifunctionality for imaging. By further modifying AuNC@BSA with additional imaging materials, their application could be extended to various types of medical imaging instruments. Nonetheless, our findings showed that each of the current nanomaterials exhibited excellent abilities for imaging cartilage with their predominant imaging modalities, but their versatility was not comparable to that of AuNC@BSA-Gd-I. Thus, AuNC@BSA-Gd-I could be served as a valuable tool in multimodal imaging strategies for cartilage assessment.
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Opioid use disorder is a chronic relapsing disorder encompassing misuse, dependence, and addiction to opioid drugs. Long term maintenance of associations between the reinforcing effects of the drug and the cues associated with its intake are a leading cause of relapse. Indeed, exposure to the salient drug-associated cues can lead to drug cravings and drug seeking behavior. The dorsal hippocampus (dHPC) and locus coeruleus (LC) have emerged as important structures for linking the subjective rewarding effects of opioids with environmental cues. However, their role in cue-induced reinstatement of opioid use remains to be further elucidated. In this study, we showed that chemogenetic inhibition of excitatory dHPC neurons during re-exposure to drug-associated cues significantly attenuates cue-induced reinstatement of morphine-seeking behavior. In addition, the same manipulation reduced reinstatement of sucrose-seeking behavior but failed to alter memory recall in the object location task. Finally, intact activity of tyrosine hydroxylase (TH) LC-dHPCTh afferents is necessary to drive cue induced reinstatement of morphine-seeking as inhibition of this pathway blunts cue-induced drug-seeking behavior. Altogether, these studies show an important role of the dHPC and LC-dHPCTh pathway in mediating cue-induced reinstatement of opioid seeking.
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Señales (Psicología) , Comportamiento de Búsqueda de Drogas , Hipocampo , Locus Coeruleus , Autoadministración , Animales , Locus Coeruleus/efectos de los fármacos , Locus Coeruleus/metabolismo , Masculino , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Ratas , Femenino , Comportamiento de Búsqueda de Drogas/efectos de los fármacos , Comportamiento de Búsqueda de Drogas/fisiología , Morfina/farmacología , Morfina/administración & dosificación , Ratas Sprague-Dawley , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Analgésicos Opioides/farmacología , Analgésicos Opioides/administración & dosificación , Trastornos Relacionados con Opioides/fisiopatología , Extinción Psicológica/efectos de los fármacos , Extinción Psicológica/fisiología , Condicionamiento Operante/efectos de los fármacos , Condicionamiento Operante/fisiologíaRESUMEN
O estudo objetiva revisar na literatura científica acerca das práticas corporais e o consumo de álcool e drogas a partir do comportamento desviante. Trata-se de uma revisão sistemática nas bases de dados MEDLINE, Scielo, Scopus, Web of Science e SportDiscus, utilizando os descritores e palavras-chave "lazer desviante", "sociologia do desvio", "práticas corporais", "álcool" e "drogas". Os critérios de inclusão foram artigos originais, estudos publicados em periódicos nacionais e internacionais. Vinte estudos publicados em periódicos foram analisados minuciosamente. Os estudos encontrados foram organizados em categorias de acordo com a temática trabalhada: i) lazer, práticas corporais e comportamento desviante em adolescentes e adultos; ii) práticas corporais e comportamento desviante no âmbito do trabalho, e iii) práticas corporais e comportamento desviante em diferentes grupos. As práticas corporais foram vistas como aspecto que podem auxiliar na prevenção de uso de álcool e drogas, mas que sejam direcionadas as formas de prevenção.
The study aims to review in the scientific literature about the corporal practices and the consumption of alcohol and drugs from the deviant behavior. It is a systematic review in the MEDLINE, Scielo, Scopus, Web of Science and SportDiscus databases, using the descriptors and keywords "deviant leisure", "deviant sociology", "corporal practices", "alcohol" and "drugs". The inclusion criteria were original articles, studies published in national and international journals. Twenty studies published in journals were analyzed in detail. The studies were organized in categories according to the theme: i) leisure, body practices and deviant behavior in adolescents and adults; ii) body practices and deviant behavior in the work area; and iii) corporal practices and deviant behavior in different groups. The body practices were seen as aspect that can aid in the prevention of alcohol and drug use, but that are directed the forms of prevention.
El estudio del objetivo es revisar la literatura científica sobre las prácticas corporales y el consumo de alcohol y drogas de la conducta desviada. Se trata de una revisión sistemática en MEDLINE, SciELO, Scopus, Web of Science y SportDiscus utilizando descriptores y palabras clave "ocio desviada", "sociología de la desviación", "prácticas corporales", "alcohol" y "drogas". Los criterios de inclusión fueron artículos originales, estudios publicados en revistas nacionales e internacionales. Se analizaron veinte estudios publicados en revistas. Los estudios encontrados fueron organizados en categorías de acuerdo con la temática trabajado: i) el ocio, las prácticas corporales y la conducta desviada en adolescentes y adultos; ii) el cuerpo y prácticas desviadas en el trabajo, y iii) las prácticas corporales y la conducta desviada en diferentes grupos. Las prácticas corporales fueron vistos como un aspecto que puede ayudar en la prevención de alcohol y drogas, pero que las formas de prevención se dirigen.
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Terapias Complementarias , Trastornos Relacionados con Sustancias/prevención & control , Alcoholismo/prevención & control , Actividades RecreativasRESUMEN
O propósito deste estudo foi analisar a associação entre força muscular e aptidão cardiorrespiratória em diferentes grupos etários. Duzentos e trinta e seis participantes (75 homens e 161 mulheres) de 40 a 84 anos foram divididos em quatro grupos etários: 40-49, 50-59, 60-69, ≥ 70 anos. A força muscular foi avaliada pelo teste de força de preensão manual (FPM), enquanto a aptidão cardiorrespiratória foi estimada pela distância percorrida no teste de caminhada de 6-min. Uma correlação positiva e significante foi encontrada entre a FPM e distância percorrida no teste de caminhada de 6-min somente no grupo ≥ 70 anos (r = 0,51; P = 0,01). Quando combinados em um modelo de regressão múltipla, a FPM (P = 0,01) e o gênero (P = 0,36) explicaram 47,4% da variância na distância percorrida no teste de caminhada de 6-min no grupo ≥ 70 anos. Os resultados sugerem que a força muscular parece ser um importante determinante da aptidão cardiorrespiratória em indivíduos ≥ 70 anos, independente do gênero.
The purpose of this study was to analyze the association between muscular strength and cardiorespiratory fitness in different age groups. Two hundred thirty-six subjects (75 men and 161 women) from 40 to 84 years old were divided in four age groups: 40-49, 50-59, 60-69, and ≥ 70 years old. Muscular strength was assessed by handgrip (HG), while cardiorespiratory fitness was estimated by the distance walked in the 6-min walk test. A positive significant correlation was found between HG and distance walked in the 6-min walk test only in the ≥ 70 years group (r = 0.51; P = 0.01). A multiple regression analysis combining HG (P = 0.01) and gender (P = 0.36) explained 47.4% of the variance in the distance walked in the 6-min walk test in the ≥ 70 group. This result suggest that muscular strength seems to be an important determinant of cardiorespiratory fitness in individuals 70 years and older, independent of gender.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano , Envejecimiento , Ejercicio FísicoRESUMEN
Abstract The aim of this study was to examine the reliability of the 6-minute walk test (6MWT) and post-exercise cardiac autonomic markers in physically active and sedentary older women. Eighteen physically active older women (64.2±3.1 years; 63.0±2.7 kg; 1.52±0.06 m; 26.9±2.7 kg.m-2) who performed Tai Chi Chuan for at least 6 months, and 18 sedentary older women (64.0±3.7 years; 63.8±8.9 kg; 1.49±0.05 m; 28.4±3.5 kg.m-2) were submitted to 6MWT in two separate occasions. Immediately after 6MWT, heart rate recovery at one (HRR1’) and two minutes (HRR2’), as well as the heart rate variability (HRV) were recorded. Reliability was verified by intraclass correlation coefficient (ICC) with 95% confidence interval, Bland-Altman plots were used as a measure of agreement, and coefficient of variation (CV) was calculated. High reliability (ICC=0.86) was found for performance in 6MWT (528.8 ± 71.4 m and 473.2 ± 62.4 m; CV=7.9 and VC=8.5%) in both groups. Likewise, high reliability (ICC≥0.84 and ICC≥0.80) was found for HRR 1’ (29.0±11.0 bpm and 17.0±8.0 bpm; VC=30.1% and VC =40.2%) and HRR 2’ (36.0±10.0 bpm and 24.0±9.0 bpm; VC =23.7% and VC =22.8%) in both groups. Regarding HRV, moderate reliability was found in the active group (CCI≥0.57; VC =35-47%), while moderate-high reliability was found in the sedentary group (CCI=0.65-0.76; VC=34-69%). Agreement was found for all variables analyzed. In conclusion, post-exercise 6MWT, HRR, and HRV are reliable tools to assess functional capacity and cardiac autonomic control in physically active and sedentary older women.
Resumo Objetivou-se verificar a reprodutibilidade do teste de caminhada de 6 minutos (TC6) e de marcadores autonômicos cardíacos pós-esforço em idosas fisicamente ativas e sedentárias. Dezoito idosas ativas (64,2 ± 3,1 anos; 63,0 ± 2,7 kg; 1,52 ± 0,06 m; 26,9 ± 2,7 kg.m-2) praticantes de Tai Chi Chuan (≥6 meses de prática) e 18 idosas sedentárias (64,0 ± 3,7 anos; 63,8 ± 8,9 kg; 1,49 ± 0,05 m; 28,4 ± 3,5 kg.m-2) foram submetidas a dois TC6 com uma semana de intervalo. Foram medidas a frequência cardíaca de recuperação (FCR) de um e dois minutos (FCR1’ e FCR2’, respectivamente) e variabilidade da frequência cardíaca (VFC) pós-esforço. A reprodutibilidade foi verificada pelos: coeficiente de correlação intraclasse (CCI) com 95% de intervalo de confiança; análise de concordância de Bland-Altman; e coeficiente de variação (CV). O desempenho no TC6 (528,8±71,4 m e 473,2±62,4 m; CV=7,9% e CV=8,5%) apresentou alta reprodutibilidade (CCI=0,86) em idosas ativas e sedentárias, respectivamente. Similarmente, as medidas pós-esforço da FCR1’ (29,0±11,0 bpm e 17,0±8,0 bpm; CV=30,1% e CV=40,2%) e FCR2’ (36,0±10,0 bpm e 24,0±9,0 bpm; CV=23,7% e CV=22,8%) apresentaram alta reprodutibilidade (CCI≥0,84 e CCI≥0,80) em ambos os grupos. Quanto a VFC verificou-se reprodutibilidade moderada (CCI≥0,57; CV=35-47%) em idosas ativas e moderada-alta nas sedentárias (CCI=0,65-0,76; CV=34-69%). Todas as variáveis apresentaram concordância em ambos os grupos. Conclui-se que o TC6, FCR e VFC pós-esforço são instrumentos reprodutíveis na avaliação da capacidade funcional e controle autonômico cardíaco em idosas ativas e sedentárias.
RESUMEN
Este estudo qualitativo objetivou comparar os resultados referentes ao comportamento pró-ambiental obtidos com idosos praticantes de atividades de aventura com os dos condutores desta vivência. A Escala de Ecocentrismo e Antropocentrismo (THOMPSON; BARTON, 1994) foi aplicada a amostras intencionais de idosos praticantes e de adultos jovens condutores de atividades de aventura na natureza. Os dados analisados descritivamente por Análise de Conteúdo indicam que idosos e adultos jovens classificam-se na dimensão ecocêntrica, porém, idosos são mais antropocêntricos e apáticos ambientais. Sugerem-se novos estudos para subsidiar novas estratégias de ação no campo da Motricidade Humana, para estimular o desenvolvimento do comportamento pró-ambiental.
This qualitative study aimed at comparing results regarding pro-environmental behavior of elderly practitioners and conductors of adventure activities. The Ecocentrism and Anthropocentrism Scale (THOMPSON; BARTON, 1994) was applied to intentional samples of elderly practitioners and young adult conductors of adventure activities in nature. Data were descriptively analyzed by content analysis and indicate that elderly and younger adults are included in the ecocentric dimension. However, the former are more anthropocentric and environmentally apathetic. New studies are suggested to subsidize new action strategies in the Human Motricity field, to stimulate the development of pro-environmental behavior.
Este estudio cualitativo tuvo como objetivo comparar los resultados referentes al comportamiento proambiental obtenido con personas mayores practicantes de actividades de aventura y con los conductores de dichas actividades. La Escala de Ecocenrismo y Antropocentrismo (THOMPSON; BARTON, 1994) se aplicó a muestras intencionales de mayores y adultos jóvenes conductores de actividades de aventura en la naturaleza. Los datos, analizados descriptivamente por Análisis de Contenido, indican que personas mayores y adultos jóvenes son clasificados en la dimensión ecocéntrica, sin embargo, los mayores son más antropocéntricos y apáticos con el ambiente. Se proponen nuevos estudios para apoyar nuevas estrategias de actuación en el campo de la Motricidad Humana, para estimular el desarrollo del comportamiento proambiental.