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Rumination, or thinking repetitively about one's distress, is a risk factor for posttraumatic stress disorder (PTSD). Current theories suggest that rumination contributes to PTSD symptoms directly, by increasing negative reactions to trauma cues (i.e., symptom exacerbation), or represents a form of cognitive avoidance, if verbal ruminations are less distressing than trauma imagery. The goal of this study was to test the symptom exacerbation and cognitive avoidance accounts of trauma-focused rumination. We recruited 135 trauma-exposed participants (n = 60 diagnosed with PTSD) and randomly assigned them to ruminate about their trauma, distract themselves, or engage in trauma imagery. For individuals with and without PTSD, rumination led to larger increases in subjective distress (i.e., negative affect, fear, sadness, subjective arousal, valence) than distraction, ηp 2 s = .04-.13, but there were no differences between rumination and imagery ηp 2 s = .001-.02. We found no evidence that rumination or imagery elicited physiological arousal, ds = 0.01-0.19, but did find that distraction reduced general physiological arousal, as measured by heart rate, relative to baseline, d = 0.84, which may be due to increases in parasympathetic nervous system activity (i.e., respiratory sinus arrhythmia), d = 0.33. These findings offer no support for the avoidant function of rumination in PTSD. Instead, the findings were consistent with symptom exacerbation, indicating that rumination leads directly to emotional reactivity to trauma reminders and may be a fruitful target in PTSD intervention.
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Transtornos de Estresse Pós-Traumáticos , Humanos , Nível de Alerta , Medo , Imagens, Psicoterapia , Transtornos de Estresse Pós-Traumáticos/psicologia , Exacerbação dos SintomasRESUMO
It is currently challenging to analyze single-cell data consisting of many cells and samples, and to address variations arising from batch effects and different sample preparations. For this purpose, we present SAUCIE, a deep neural network that combines parallelization and scalability offered by neural networks, with the deep representation of data that can be learned by them to perform many single-cell data analysis tasks. Our regularizations (penalties) render features learned in hidden layers of the neural network interpretable. On large, multi-patient datasets, SAUCIE's various hidden layers contain denoised and batch-corrected data, a low-dimensional visualization and unsupervised clustering, as well as other information that can be used to explore the data. We analyze a 180-sample dataset consisting of 11 million T cells from dengue patients in India, measured with mass cytometry. SAUCIE can batch correct and identify cluster-based signatures of acute dengue infection and create a patient manifold, stratifying immune response to dengue.
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Redes Neurais de Computação , Análise de Célula Única , Análise por Conglomerados , Dengue/imunologia , Humanos , Linfócitos T/imunologiaRESUMO
BACKGROUND: Reducing the burden of unsafe abortion rests considerably on women's ability to access appropriate and timely treatment or services. A critical component of that care relies on a functional supply chain to ensure availability of abortion drugs and supplies within the health system. Disruptions in the supply of medical abortion drugs delay provision of abortion services and can increase the risks to a woman's health. We examine the ways in which supply chain management (SCM) affects women's ability to access safe and timely abortion to meet their reproductive health needs and highlight the gap in evaluation research on which SCM interventions best improve access to safe abortion care. SCM comprises a critical component of efficient and sustainable abortion service provision and is a requisite for expansion of services. Furthermore, governments are responsible for safeguarding links in the abortion supply chain, from registration to distribution of abortion drugs and supplies. Strategic public-private partnerships and use of innovative local or community-based distribution mechanisms can strengthen supply chain systems. Finally, alternatives to the pull-based models of distribution could alleviate bottlenecks in the final steps of abortion supply chains. Programs aimed at increasing access to safe and comprehensive abortion care must include SCM as a foundational component of service provision. Without access to a sustainable and affordable supply of abortion drugs and equipment, any attempt at providing abortion services will be critically limited. More implementation research is needed to identify the most effective interventions for improving SCM.
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Aborto Induzido , Aborto Legal , Acessibilidade aos Serviços de Saúde , Feminino , Pesquisa sobre Serviços de Saúde , Humanos , Gravidez , Saúde ReprodutivaRESUMO
OBJECTIVE: The current study investigated whether rumination accounts for the relationship between multiple aspects of emotion regulation (ER) difficulties and posttraumatic stress disorder (PTSD) severity. METHOD: Participants were 90 community members (43% diagnosed with PTSD; Mage = 26.7, 86% female) who were interviewed using the Clinician-Administered PTSD Scale-5 and completed self-reported measures of ER and rumination. RESULTS: The indirect effect of rumination completely accounted for the relationship between overall ER difficulties and PTSD severity. This finding was replicated for three unique aspects of ER (i.e., nonacceptance of negative emotions, impulse control difficulties under emotional distress, and the ability to maintain goal-oriented behavior under emotional distress). Reverse models testing the indirect effect of ER on the link between rumination and PTSD were nonsignificant. CONCLUSIONS: Rumination is an important cognitive process linking specific aspects of ER difficulties to PTSD. Clinical interventions focused on improving ER abilities among those with PTSD may benefit from targeting rumination.
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Regulação Emocional , Ruminação Cognitiva , Transtornos de Estresse Pós-Traumáticos/psicologia , Adolescente , Adulto , Estudos Transversais , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Objetivos , Humanos , Comportamento Impulsivo , Masculino , Pessoa de Meia-Idade , Autorrelato , Estados Unidos , Adulto JovemRESUMO
Animals employ hair bundles on hair cells to detect flow, vibrations and gravity. Hair bundles on sea anemone tentacles detect nearby vibrations in the water column produced by prey movements and then regulate discharge of cnidae to capture prey. This study investigated: (1) the progressive effects of periodic water flow on hair bundle morphology and density of hair bundles and cnidae in sea anemones, (2) the reversibility of the flow response and (3) the ability of the response to be expedited with increased flow duration. Linear density of hair bundles along tentacles and each hair bundle's dimensions was measured in anemones exposed to flow and in the absence of flow. With increasing numbers of days of flow, hair bundles in anemones exposed to flow for 1 h every weekday for 20 days increased in density and grew longer and wider at bases and middles, whereas controls did not. Time courses fit to a linear function exhibited significantly larger positive slopes from animals exposed to flow compared with controls. Hair bundles in anemones exposed to flow for 3 h each day increased in linear density, length, base width and middle width after 10 days of flow and returned to control levels after 10 days following cessation of flow. In addition, there was a trend for an increase in density of cnidae with flow. Therefore, anemone hair bundles are dynamically and reversibly modified by periodic, moderate flow to become more abundant and robust. These findings may have relevance to hair cells in acoustico-lateralis systems of higher animals.
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Mecanorreceptores/fisiologia , Anêmonas-do-Mar/fisiologia , Movimentos da Água , Animais , Distribuição Aleatória , VibraçãoRESUMO
In this article, we discuss the immunogenicity of radiation-induced cell death and describe the innate immune signaling pathways that precede adaptive antitumoral immunity. The innate and adaptive immune systems work in concert to generate systemic immune responses. In the setting of cancer, DNA damage caused by radiotherapy activates the innate immune system while tumor cell death liberates antigen that serves as a target for adaptive immunity. The immunomodulatory effects of radiation have been investigated in preclinical models; here we summarize the available data, with particular attention to the effects of radiotherapy timing, location, dose, and fractionation strategy on the antitumoral immune response. We synthesize preclinical and clinical information regarding the potential superiority of hypofractionated radiation for induction of proinflammatory responses. Although many questions remain, early successes with combining immunotherapy and radiotherapy merit further inquiry into the dose and fractionation strategies best able to activate and sustain an antitumoral response.
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Neoplasias/imunologia , Neoplasias/radioterapia , Imunidade Adaptativa , Morte Celular/efeitos da radiação , Fracionamento da Dose de Radiação , Humanos , Radioterapia/métodosRESUMO
Cytosolic DNA-sensing pathways that signal via Stimulator of interferon genes (STING) mediate immunity to pathogens and also promote autoimmune pathology in DNaseII- and DNaseIII-deficient mice. In contrast, we report here that STING potently suppresses inflammation in a model of systemic lupus erythematosus (SLE). Lymphoid hypertrophy, autoantibody production, serum cytokine levels, and other indicators of immune activation were markedly increased in STING-deficient autoimmune-prone mice compared with STING-sufficient littermates. As a result, STING-deficient autoimmune-prone mice had significantly shorter lifespans than controls. Importantly, Toll-like receptor (TLR)-dependent systemic inflammation during 2,6,10,14-tetramethylpentadecane (TMPD)-mediated peritonitis was similarly aggravated in STING-deficient mice. Mechanistically, STING-deficient macrophages failed to express negative regulators of immune activation and thus were hyperresponsive to TLR ligands, producing abnormally high levels of proinflammatory cytokines. This hyperreactivity corresponds to dramatically elevated numbers of inflammatory macrophages and granulocytes in vivo. Collectively these findings reveal an unexpected negative regulatory role for STING, having important implications for STING-directed therapies.
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Autoimunidade/fisiologia , Proteínas de Membrana/fisiologia , Animais , Autoanticorpos/biossíntese , Células Dendríticas/imunologia , Regulação da Expressão Gênica/fisiologia , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/fisiologia , Interferons/fisiologia , Ativação Linfocitária , Proteínas de Membrana/genética , CamundongosRESUMO
Few studies have examined potential differences between social anxiety disorder (SAD) and generalised anxiety disorder (GAD) in the sensitivity to detect emotional expressions. The present study aims to compare the detection of emotional expressions in SAD and GAD. Participants with a primary diagnosis of GAD (n = 46), SAD (n = 70), and controls (n = 118) completed a morph movies task. The task presented faces expressing increasing degrees of emotional intensity, slowly changing from a neutral to a full-intensity happy, sad, or angry expressions. Participants used a slide bar to view the movie frames from left to right, and to stop at the first frame where they perceived an emotion. The frame selected thus indicated the intensity of emotion required to identify the facial expression. Participants with GAD detected the onset of facial emotions at lower intensity of emotion than participants with SAD (p = 0.002) and controls (p = 0.039). In a multiple regression analysis controlling for age, race, and depressive symptom severity, lower frame at which the emotion was detected was independently associated and GAD diagnosis (B = -5.73, SE = 1.74, p < 0.01). Our findings suggest that individuals with GAD exhibit enhanced detection of facial emotions compared to those with SAD or controls.
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Transtornos de Ansiedade/psicologia , Expressão Facial , Reconhecimento Psicológico , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Estimulação Luminosa , Adulto JovemRESUMO
AIMS: Detraining refers to a loss of training adaptations resulting from reductions in training stimulus due to illness, injury, or active recovery breaks in a training cycle and is associated with a reduction in left ventricular mass (LVM). The purpose of this study was to conduct a systematic review and meta-analysis to determine the influence of detraining on LVM in endurance-trained, healthy individuals. METHODS AND RESULTS: Using electronic databases (e.g. EMBASE and MEDLINE), a literature search was performed looking for prospective detraining studies in humans. Inclusion criteria were adults, endurance-trained individuals with no known chronic disease, detraining intervention >1 week, and pre- and post-detraining LVM reported. A pooled statistic for random effects was used to assess changes in LVM with detraining. Fifteen investigations (19 analyses) with a total of 196 participants (ages 18-55 years, 15% female) met inclusion criteria, with detraining ranging between 1.4 and 15 weeks. The meta-analysis revealed a significant reduction in LVM with detraining (standardized mean difference = -0.586; 95% confidence interval = -0.817, -0.355; P < 0.001). Independently, length of detraining was not correlated with the change in LVM. However, a meta-regression model revealed length of the detraining, when training status was accounted for, was associated with the reduction of LVM (Q = 15.20, df = 3, P = 0.0017). Highly trained/elite athletes had greater reductions in LVM compared with recreational and newly trained individuals (P < 0.01). Limitations included relatively few female participants and inconsistent reporting of intervention details. CONCLUSION: In summary, LVM is reduced following detraining of one week or more. Further research may provide a greater understanding of the effects of sex, age, and type of detraining on changes in LVM in endurance-trained individuals.
In healthy, endurance-trained individuals, detraining results in significant reductions in left ventricular mass. When accounting for training status, the length of the detraining period is positively associated with reductions in left ventricular mass. Limited research on this topic hinders the ability to assess sex differences or the impact of the type of detraining (i.e. only activities of daily living vs. reduced training load) on the response to detraining.
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Treino Aeróbico , Função Ventricular Esquerda , Humanos , Atletas , Resistência Física , Estudos ProspectivosRESUMO
PURPOSE: Hypofractionated radiation therapy (HFRT) is a common treatment for thoracic tumors, typically delivered as 60 Gy in 15 fractions. We aimed to identify dosimetric risk factors associated with radiation pneumonitis in patients receiving HFRT at 4 Gy per fraction, focusing on lung V20, mean lung dose (MLD), and lung V5 as potential predictors of grade ≥2 pneumonitis. METHODS AND MATERIALS: All patients were treated with thoracic HFRT to 60 Gy in 15 fractions or 72 Gy in 18 fractions at a single health care system from 2013 to 2020. Tumors near critical structures (trachea, proximal tracheobronchial tree, esophagus, spinal cord, or heart) were considered central (within 2 cm), and those closer were classified as ultracentral (within 1 cm). The primary endpoint was grade ≥2 pneumonitis. Logistic regression analyses, adjusting for target size and dosimetric variables, were used to establish a dose threshold associated with <20% risk of grade ≥2 pneumonitis. RESULTS: During a median 24.3-month follow-up, 18 patients (16.8%) developed grade ≥2 radiation pneumonitis, with no significant difference between the 2 dose regimens (17.3% vs 16.3%, P = .88). Four patients (3.7%) experienced grade ≥3 pneumonitis, including 2 grade 5 cases. Patients with grade ≥2 pneumonitis had significantly higher lung V20 (mean 23.4% vs 14.5%, P < .001), MLD (mean 13.0 Gy vs 9.5 Gy, P < .001), and lung V5 (mean 49.6% vs 40.6%, P = .01). Dose thresholds for a 20% risk of grade ≥2 pneumonitis were lung V20 <17.7%, MLD <10.6 Gy, and V5 <41.3%. Multivariable analysis revealed a significant association between lung V20 and grade ≥2 pneumonitis (adjusted odds ratio, 1.48, P = .03). CONCLUSIONS: To minimize the risk of grade ≥2 radiation pneumonitis when delivering 4 Gy per fraction at either 60 Gy or 72 Gy, it is advisable to maintain lung V20<17.7%. MLD <10.6 Gy and V5<41.3% can also be considered as lower-priority constraints. However, additional validation is necessary before incorporating these constraints into clinical practice or trial planning guidelines.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia , Pneumonite por Radiação , Humanos , Pneumonite por Radiação/epidemiologia , Pneumonite por Radiação/etiologia , Neoplasias Pulmonares/patologia , Pulmão/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Pneumonia/complicações , Estudos Retrospectivos , Dosagem RadioterapêuticaRESUMO
Loss of NADPH oxidase (NOX2) exacerbates systemic lupus erythematosus (SLE) in mice and humans, but the mechanisms underlying this effect remain unclear. To identify the cell lineages in which NOX2 deficiency drives SLE, we employed conditional KO and chimeric approaches to delete Cybb in several hematopoietic cell lineages of MRL.Faslpr SLE-prone mice. Deletion of Cybb in macrophages/monocytes exacerbated SLE nephritis, though not to the degree observed in the Cybb global KOs. Unexpectedly, the absence of Cybb in B cells resulted in profound glomerulonephritis and interstitial nephritis, rivaling that seen with global deletion. Furthermore, we identified that NOX2 is a key regulator of TLR7, a driver of SLE pathology, both globally and specifically in B cells. This is mediated in part through suppression of TLR7-mediated NF-κB signaling in B cells. Thus, NOX2's immunomodulatory effect in SLE is orchestrated not only by its function in the myeloid compartment, but through a pivotal role in B cells by selectively inhibiting TLR7 signaling.
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Linfócitos B , Lúpus Eritematoso Sistêmico , Macrófagos , Camundongos Knockout , NADPH Oxidase 2 , Receptor 7 Toll-Like , Animais , Receptor 7 Toll-Like/metabolismo , Receptor 7 Toll-Like/genética , Camundongos , Linfócitos B/imunologia , Linfócitos B/metabolismo , NADPH Oxidase 2/metabolismo , NADPH Oxidase 2/genética , Macrófagos/imunologia , Macrófagos/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Transdução de Sinais , Feminino , Modelos Animais de Doenças , NF-kappa B/metabolismo , Nefrite Lúpica/imunologia , Nefrite Lúpica/patologia , Nefrite Lúpica/metabolismo , Nefrite Lúpica/genética , Glicoproteínas de MembranaRESUMO
Purpose: We investigated whether pulmonary metastases from historically considered radioresistant primaries would have inferior local control after radiation therapy than those from nonradioresistant nonlung primaries, and whether higher biologically effective dose assuming alpha/beta=10 (BED10) would be associated with superior local control. Methods and Materials: We identified patients treated with radiation therapy for oligometastatic or oligoprogressive pulmonary disease to 1 to 5 lung metastases from nonlung primaries in 2013 to 2020 at a single health care system. Radioresistant primary cancers included colorectal carcinoma, endometrial carcinoma, renal cell carcinoma, melanoma, and sarcoma. Nonradioresistant primary cancers included breast, bladder, esophageal, pancreas, and head and neck carcinomas. The Kaplan-Meier estimator, log-rank test, and multivariable Cox proportional hazards regression were used to compare local recurrence-free survival (LRFS), new metastasis-free survival, progression-free survival, and overall survival. Results: Among 114 patients, 73 had radioresistant primary cancers. The median total dose was 50 Gy (IQR, 50-54 Gy) and the median number of fractions was 5 (IQR, 3-5). Median follow-up time was 59.6 months. One of 41 (2.4%) patients with a nonradioresistant metastasis experienced local failure compared with 18 of 73 (24.7%) patients with radioresistant metastasis (log-rank P = .004). Among radioresistant metastases, 12 of 41 (29.2%) patients with colorectal carcinoma experienced local failure compared with 6 of 32 (18.8%) with other primaries (log-rank P = .018). BED10 ≥100 Gy was associated with decreased risk of local recurrence. On univariable analysis, BED10 ≥100 Gy (hazard ratio [HR], 0.263; 95% CI, 0.105-0.656; P = .004) was associated with higher LRFS, and colorectal primary (HR, 3.060; 95% CI, 1.204-7.777; P = .019) was associated with lower LRFS, though these were not statistically significant on multivariable analysis. Among colorectal primary patients, BED10 ≥100 Gy was associated with higher LRFS (HR, 0.266; 95% CI, 0.072-0.985; P = .047) on multivariable analysis. Conclusions: Local control after radiation therapy was encouraging for pulmonary metastases from most nonlung primaries, even for many of those classically considered to be radioresistant. Those from colorectal primaries may benefit from testing additional strategies, such as resection or systemic treatment concurrent with radiation.
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Immune related adverse events (irAEs) after immune checkpoint blockade (ICB) therapy occur in a significant proportion of cancer patients. To date, the circulating mediators of ICB-irAEs remain poorly understood. Using non-targeted mass spectrometry, here we identify the circulating bio-active lipid linoleoyl-lysophosphatidylcholine (LPC 18:2) as a modulator of ICB-irAEs. In three independent human studies of ICB treatment for solid tumor, loss of circulating LPC 18:2 preceded the development of severe irAEs across multiple organ systems. In both healthy humans and severe ICB-irAE patients, low LPC 18:2 was found to correlate with high blood neutrophilia. Reduced LPC 18:2 biosynthesis was confirmed in preclinical ICB-irAE models, and LPC 18:2 supplementation in vivo suppressed neutrophilia and tissue inflammation without impacting ICB anti-tumor response. Results indicate that circulating LPC 18:2 suppresses human ICB-irAEs, and LPC 18:2 supplementation may improve ICB outcomes by preventing severe inflammation while maintaining anti-tumor immunity.
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Background: The impact of the menstrual phases on left ventricular (LV) structure and function using 3D echocardiography and resting electrocardiogram (ECG) in healthy, eumenorrheic, and physically active females has not been investigated. Methods: sixteen females (20 y ± 2) underwent 3D echocardiography and an ECG at three time points in the menstrual cycle phases (follicular, ovulation, luteal). LV end-diastolic volume (LVEDVi), LV ejection fraction (LVEF), LV mass allometrically indexed to height2.7 (LVMi), torsion, and global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS) were evaluated. ECG data of the P and QRS waves were presented as well as axis deviation, chamber enlargement, and any rhythm abnormalities. Results: LVMi was significantly higher in the luteal phase (36.4 g/m2.7 ± 3.3) compared to the follicular (35.0 g/m2.7 ± 3.7) and ovulation (34.7 g/m2.7 ± 4.3) phases (p = 0.026). There were no differences in other indices of LV structure and function or ECG variables across all phases of the menstrual cycle or evidence of arrhythmia. Conclusions: In physically active females, there is a small but significantly higher LVMi associated with the luteal phase of the menstrual cycle with no concomitant change in LV function or ECG parameters. These findings are important to consider when conducting clinical or research serial assessments.
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STUDY OBJECTIVES: Prior work has established associations between post-traumatic stress disorder (PTSD), disrupted sleep, and cardiovascular disease (CVD), but few studies have examined health correlates of nightmares beyond risks conferred by PTSD. This study examined associations between nightmares and CVD in military veterans. METHODS: Participants were veterans (Nâ =â 3468; 77% male) serving since September 11, 2001, aged 38 years (SDâ =â 10.4); approximately 30% were diagnosed with PTSD. Nightmare frequency and severity were assessed using the Davidson Trauma Scale (DTS). Self-reported medical issues were assessed using the National Vietnam Veterans Readjustment Study Self-report Medical Questionnaire. Mental health disorders were established using the Structured Clinical Interview for DSM-IV. The sample was stratified by the presence or absence of PTSD. Within-group associations between nightmare frequency and severity and self-reported CVD conditions, adjusting for age, sex, race, current smoking, depression, and sleep duration. RESULTS: Frequent and severe nightmares during the past week were endorsed by 32% and 35% of participants, respectively. Those endorsing nightmares that were frequent, severe, and the combination thereof were more likely to also evidence high blood pressure (ORs 1.42, OR 1.56, and OR 1.47, respectively) and heart problems (OR 1.43, OR 1.48, and OR 1.59, respectively) after adjusting for PTSD diagnosis and other covariates. CONCLUSIONS: Nightmare frequency and severity among veterans are associated with cardiovascular conditions, even after controlling for PTSD diagnosis. Study findings suggest that nightmares may be an independent risk factor for CVD. Additional research is needed to validate these findings using confirmed diagnoses and explore potential mechanisms.
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Doenças Cardiovasculares , Transtornos de Estresse Pós-Traumáticos , Veteranos , Humanos , Masculino , Feminino , Sonhos/psicologia , Doenças Cardiovasculares/complicações , Transtornos de Estresse Pós-Traumáticos/psicologia , Veteranos/psicologia , Fatores de RiscoRESUMO
NADPH oxidase deficiency exacerbates lupus in murine models and patients, but the mechanisms remain unknown. It is hypothesized that NADPH oxidase suppresses autoimmunity by facilitating dead cell clearance via LC3-associated phagocytosis (LAP). The absence of LAP reportedly causes an autoinflammatory syndrome in aged, nonautoimmune mice. Prior work implicated cytochrome b-245, ß polypeptide (CYBB), a component of the NADPH oxidase complex, and the RUN and cysteine-rich domain-containing Beclin 1-interacting protein (RUBICON) as requisite for LAP. To test the hypothesis that NADPH oxidase deficiency exacerbates lupus via a defect in LAP, we deleted Rubicon in the B6.Sle1.Yaa and MRL.Faslpr lupus mouse models. Under this hypothesis, RUBICON deficiency should phenocopy NADPH oxidase deficiency, as both work in the same pathway. However, we observed the opposite - RUBICON deficiency resulted in reduced mortality, renal disease, and autoantibody titers to RNA-associated autoantigens. Given that our data contradict the published role for LAP in autoimmunity, we assessed whether CYBB and RUBICON are requisite for LAP. We found that LAP is not dependent on either of these 2 pathways. To our knowledge, our data reveal RUBICON as a novel regulator of SLE, possibly by a B cell-intrinsic mechanism, but do not support a role for LAP in lupus.
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Autofagia , Fagossomos , Idoso , Animais , Modelos Animais de Doenças , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , NADPH Oxidases/metabolismo , FagocitoseRESUMO
Respiratory sinus arrhythmia (RSA) reactivity is thought to indicate how adaptively one responds to stress. RSA reactivity has been examined across anxiety disorders and posttraumatic stress disorder (PTSD), to better understand the psychophysiological stress response of these disorders. The current state of the literature is mixed, and the association between RSA reactivity and PTSD/anxiety is unclear. This review examines RSA reactivity in response to laboratory stressor tasks across samples with anxiety and PTSD. Results indicated a complex literature that may suggest an association between anxiety/PTSD and RSA reactivity. There is evidence to suggest a pattern of heightened RSA withdrawal in PTSD and trait anxious samples. There was little evidence to suggest a heightened RSA withdrawal pattern in other anxiety disorders. This review also highlights methodological considerations which may allow for clearer interpretations of RSA reactivity. The current literature includes heterogeneity across stressor tasks, RSA measures, and comorbidities that complicates interpretation of results. Studies using samples with comorbid depression produce more consistent evidence of heightened RSA withdrawal in anxiety/PTSD. Future directions for understanding the contribution of these variables (i.e., stressor tasks, RSA measures, comorbid depression) and mechanisms contributing to the possible association between RSA reactivity and anxiety/PTSD are considered.
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Arritmia Sinusal Respiratória , Transtornos de Estresse Pós-Traumáticos , Transtorno da Personalidade Antissocial , Ansiedade , Transtornos de Ansiedade , HumanosRESUMO
Improved understanding of host antiviral defense and antitumor immunity have elucidated molecular pathways important to both processes. During viral infection, RNA or DNA in the host cell serves as a danger signal that initiates the antiviral response. Recent studies have elucidated similarities in the signaling pathways activated by viruses and the signaling pathways induced by tumor DNA that is released into the cytoplasm of irradiated tumor cells. Both the host defense to viral infection and the sterile inflammation provoked by radiotherapy induce a type I interferon response that is necessary for pathogen control and immune-mediated tumor control, respectively. These findings have led to the hypothesis that radiotherapy employs a form of viral mimicry.
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Antivirais , Imunidade Inata , Humanos , Transdução de SinaisRESUMO
PURPOSE: On June 13 to 14, 2019, the American Society for Radiation Oncology and the Radiological Society of North America convened a workshop on the treatment of oligometastatic disease in Washington, DC. The workshop was initiated for several reasons. First, oligometastatic disease is of increasing academic and community interest and has been identified by the American Society for Radiation Oncology membership as a top research priority. Second, emerging imaging and diagnostic technologies are more readily defining and detecting oligometastatic disease, making contemporary discussion of oligometastatic disease especially relevant. Third, radiosurgery and radiation in general are theorized to be ideal noninvasive therapy for the treatment of oligometastatic disease. Finally, innovations in targeted therapy and immune therapy have the potential to reverse widely disseminating disease into an oligometastatic state. METHODS AND MATERIALS: The workshop was organized into 2 keynote addresses, 6 scientific sessions, and 3 group discussions during an end-of-workshop breakout session. New scientific work was presented in the form of 4 oral presentations and a poster session. Workshop participants were charged with attempting to answer 3 critical questions: (1) Can we refine the clinical and biological definitions of oligometastatic disease; (2) how can we better treat oligometastatic disease; and (3) what clinical trials are needed? RESULTS: Here, we present the proceedings of the workshop. CONCLUSIONS: The clinical implications of improved treatment of oligometastatic disease are enormous and immediate. Radiation oncology and diagnostic radiology should rightly be at the forefront of the characterization and treatment of oligometastatic disease. Focused effort is required so that we can translate current efforts of large numbers of studies with few patients to larger studies of larger impact.