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1.
Psychophysiology ; 61(5): e14513, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38339852

RESUMO

Little is known about central nervous system (CNS) responses to emotional stimuli in asthma. Nitric oxide in exhaled breath (FENO) is elevated in asthma due to allergic immune processes, but endogenous nitric oxide is also known to modulate CNS activity. We measured fMRI blood oxygen-dependent (BOLD) brain activation to negative (blood-injection-injury themes) and neutral films in 31 participants (15 with asthma). Regions-of-interest analysis was performed on key areas relevant to central adaptive control, threat processing, or salience networks, with dorsolateral prefrontal cortex (PFC), anterior insula, dorsal anterior cingulate cortex (dACC), amygdala, ventral striatum, ventral tegmentum, and periaqueductal gray, as well as top-down modulation of emotion, with ventrolateral and ventromedial PFC. Both groups showed less BOLD deactivation from fixation cross-baseline in the left anterior insula and bilateral ventromedial PFC for negative than neutral films, and for an additional number of areas, including the fusiform gyrus, for film versus recovery phases. Less deactivation during films followed by less recovery from deactivation was found in asthma compared to healthy controls. Changes in PCO2 did not explain these findings. FENO was positively related to BOLD activation in general, but more pronounced in healthy controls and more likely in neutral film processing. Thus, asthma is associated with altered processing of film stimuli across brain regions not limited to central adaptive control, threat processing, or salience networks. Higher levels of NO appear to facilitate CNS activity, but only in healthy controls, possibly due to allergy's masking effects on FENO.


Assuntos
Asma , Imageamento por Ressonância Magnética , Humanos , Óxido Nítrico/análise , Oxigênio , Asma/diagnóstico por imagem , Emoções/fisiologia
2.
Psychosom Med ; 85(5): 440-448, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36961348

RESUMO

OBJECTIVE: Anxiety is highly prevalent in individuals with asthma. Asthma symptoms and medication can exacerbate anxiety, and vice versa. Unfortunately, treatments of comorbid anxiety and asthma are largely lacking. A problematic feature common to both conditions is hyperventilation. It adversely affects lung function and symptoms in asthma and anxiety. We examined whether a treatment to reduce hyperventilation, shown to improve asthma symptoms, also improves anxiety in asthma patients with high anxiety. METHOD: One hundred twenty English- or Spanish-speaking adult patients with asthma were randomly assigned to either Capnometry-Assisted Respiratory Training (CART) to raise P co2 or feedback to slow respiratory rate (SLOW). Although anxiety was not an inclusion criterion, 21.7% met clinically relevant anxiety levels on the Hospital Anxiety and Depression Scale (HADS). Anxiety (HADS-A) and depression (HADS-D) scales, anxiety sensitivity (Anxiety Sensitivity Index [ASI]), and negative affect (Negative Affect Scale of the Positive Affect Negative Affect Schedule) were assessed at baseline, posttreatment, 1-month follow-up, and 6-month follow-up. RESULTS: In this secondary analysis, asthma patients with high baseline anxiety showed greater reductions in ASI and PANAS-N in CART than in SLOW ( p values ≤ .005, Cohen d values ≥ 0.58). Furthermore, at 6-month follow-up, these patients also had lower ASI, PANAS-N, and HADS-D in CART than in SLOW ( p values ≤ .012, Cohen d values ≥ 0.54). Patients with low baseline anxiety did not have differential outcomes in CART than in SLOW. CONCLUSIONS: For asthma patients with high anxiety, our brief training designed to raise P co2 resulted in significant and sustained reductions in anxiety sensitivity and negative affect compared with slow-breathing training. The findings lend support for P co2 as a potential physiological target for anxiety reduction in asthma. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00975273 .


Assuntos
Asma , Hiperventilação , Adulto , Humanos , Ansiedade/etiologia , Ansiedade/terapia , Transtornos de Ansiedade/terapia , Asma/complicações , Asma/terapia , Biorretroalimentação Psicológica/métodos , Depressão
3.
J Behav Med ; 46(6): 960-972, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37227673

RESUMO

People with asthma may be particularly vulnerable to pandemic-related psychological distress, and research is needed to understand the impact of the coronavirus disease 19 (COVID-19) pandemic on their health and well-being. We sought to study the well-being of people with asthma relative to non-asthmatic controls during the COVID-19 pandemic. We also investigated asthma symptoms and COVID-19-related anxiety as potential mediators of distress. Participants completed self-report measures of psychological functioning, including anxiety, depression, stress, and burnout. Controlling for potential confounds, multiple-regression analyses examined differences in psychological health between people with and without asthma. Mediator analyses investigated the role of asthma symptoms and COVID-19-related anxiety in this relationship. 234 adults (111 with asthma, 123 without) participated in an online survey from July to November 2020. During this time, people with asthma reported higher levels of anxiety, perceived stress, and burnout symptoms compared to controls. Elevations in burnout symptoms were found beyond general anxiety and depression (sr2 = .03, p < .001). Reported symptoms typical in both asthma and COVID-19 partially mediated this relationship (Pm = .42, p < .05). People with asthma reported unique psychological challenges during the COVID-19 pandemic including elevated burnout symptoms. Experience of asthma symptoms played a key role in vulnerability to emotional exhaustion. Clinical implications include increased attention to asthma symptom burden within the context of heightened environmental stress and restricted healthcare access.

4.
Ann Behav Med ; 56(6): 645-653, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34559182

RESUMO

BACKGROUND: Vasovagal reactions (VVRs) are commonly experienced in medical situations such as blood donation. Many believe that psychosocial contagion can contribute to the development of VVRs, but this is largely clinical lore. PURPOSE: The goal of the present investigation was to examine the physiological effects of observing another experience a reaction, focusing on the potential moderating effects of empathy. METHODS: This study was part of a randomized controlled trial of behavioral techniques on the prevention of VVRs in blood donors. The sample was composed of 530 healthy university students. Measures of symptoms were obtained with the Blood Donation Reactions Inventory (BDRI) and through observation. Physiological variables were measured using respiratory capnometry and a digital blood pressure monitor. The Affective and Cognitive Measure of Empathy was administered to 230 participants. RESULTS: Donors who witnessed another experiencing a reaction were more likely to spontaneously report symptoms during the blood draw, to be treated for a reaction, to score higher on the BDRI, and to exhibit smaller compensatory heart rate increases. Donors with higher affective empathy reported more symptoms, exhibited hyperventilation, and were more likely to be treated. Donors with higher cognitive empathy were less likely to require treatment if they witnessed a reaction. CONCLUSION: These results suggest that psychosocial contagion of physical symptoms can occur. The moderating effects of empathy differed depending on the subtype of empathy. Perhaps a better cognitive understanding of how other people are feeling functions as a coping response, whereas feeling sympathetic about others' distress increases one's own.


Assuntos
Doadores de Sangue , Síncope Vasovagal , Doadores de Sangue/psicologia , Empatia , Frequência Cardíaca , Humanos , Motivação , Síncope Vasovagal/prevenção & controle
5.
Liver Int ; 41(12): 3011-3023, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34459091

RESUMO

BACKGROUND & AIM: The development of hepatocellular carcinoma (HCC) is associated with the formation of communication networks leading to the recruitment of disease-modifying macrophages. However, how oncogenes in tumour cells control paracrine communication is not fully understood. METHODS: Transgenic mice with liver-specific expression of the constitutively active yes-associated protein (YAPS127A ) or an orthotopic implantation model served as tumour models. FACS-sorted F4/80+ /CD11bdim /CD146- /retinoid- macrophages from healthy and tumour-bearing livers were used for transcriptomic profiling. Expression data of 242 human HCCs and a tissue microarray consisting of 91 HCCs and seven liver tissues were analyzed. RESULTS: Screening of primary tumour cells expressing YAPS127A identified CC chemokine ligand 2 (Ccl2) as a macrophage chemoattractant, whose expression was regulated in a YAP/TEA domain family member 4 (TEAD4)-dependent manner. Ccl2 expression was associated with a loss of Kupffer cells (KCs) and an increase in immature macrophages (Mɸimm ) in hepatocarcinogenesis. Recruited Mɸimm were characterized by a lack of functional polarization (M0 signature) and high expression of the Ccl2 receptors C-C motif chemokine receptor 2 (Ccr2), C-X3-C motif chemokine receptor 1 (Cx3cr1) and pro-angiogenic platelet-derived growth factors (Pdgfa/Pdgfb). Mɸimm formed cellular clusters in the perivascular space, which correlated with vascular morphometric changes indicative for angiogenesis. In human HCCs, the M0 signature served as an identifier for poor clinical outcome and CCL2 correlated with YAP expression and vascular network formation. CONCLUSIONS: In conclusion, YAP/TEAD4-regulated Ccl2 associates with perivascular recruitment of unpolarized Mɸimm and may contribute to a proangiogenic microenvironment in liver cancer.


Assuntos
Carcinoma Hepatocelular , Quimiocina CCL2 , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/patologia , Proteínas de Ciclo Celular , Quimiocina CCL2/metabolismo , Humanos , Células de Kupffer/metabolismo , Ligantes , Neoplasias Hepáticas/patologia , Macrófagos/metabolismo , Camundongos , Receptores CCR2/genética , Receptores CCR2/metabolismo , Fatores de Transcrição , Microambiente Tumoral , Remodelação Vascular , Proteínas de Sinalização YAP
6.
J Asthma ; 58(6): 825-833, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32089019

RESUMO

Background: Perceptions of asthma triggers provide important guidance for patients' disease management. A psychometrically valid instrument, the Asthma Trigger Inventory (ATI), is available in English and German language versions, however, a version in Spanish as major world language has been missing.Method: A Spanish-language version of the ATI was evaluated in 339 adult patients with asthma, 223 of these in Peru and 107 in the USA. Principal Component analysis (PCA) with Varimax rotation was used to identify coherent trigger domains across and within samples. Resulting subscales were evaluated for internal consistency.Results: PCA suggested differences in factor structures between sites. Whereas the USA sample largely replicated original factors for animal allergens, pollen allergens, physical activity, air pollution/irritants, infections, and psychology, the initial analysis of the Peru sample suggested substantial overlap of air pollution/irritant, infection, and allergen items. Subsequent analysis of an expanded research form of the ATI for the Peru site culminated in extraction of five factors related to psychology, climate/temperature, combined pollen and animal allergens, physical activity, and infection. Internal consistencies were in an acceptable to excellent range (α = 0.74 to 0.94). Additional free trigger responses confirmed the importance of climate variables for patients in Peru. Psychological triggers were reported by 26% (Peru) and 31% (USA) of patients.Conclusion: Coherent trigger domains are readily identified and measured reliably by a Spanish-language ATI version. However, factor structures vary between samples from different Hispanic/Latino cultural and geographic domains. Culturally adapted versions of this instrument are therefore required for Hispanic/Latino population studies.


Assuntos
Asma/epidemiologia , Asma/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Poluição do Ar/efeitos adversos , Alérgenos/efeitos adversos , Competência Cultural , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peru/epidemiologia , Análise de Componente Principal , Psicometria , Reprodutibilidade dos Testes , Fatores Socioeconômicos , Inquéritos e Questionários , Tradução , Estados Unidos/epidemiologia , Adulto Jovem
7.
Dev Psychobiol ; 63(2): 350-363, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32658309

RESUMO

Maternal hypothalamic-pituitary-adrenal axis activity may prenatally program sex-specific stress-response pathways. We investigated associations between maternal cortisol during pregnancy and infant parasympathetic responsivity to stress among 204 mother-infant pairs. Cortisol indices included 3rd trimester hair cortisol, as well as diurnal slope and area under the curve, derived from saliva samples collected during pregnancy. Mother-infant dyads participated in the Repeated Still-Face Paradigm (SFP-R) at age 6 months. We calculated respiration-adjusted respiratory sinus arrhythmia (RSAc ), an indicator of parasympathetic activation, from infant respiration and cardiac activity measured during the SFP-R. We used multivariable linear mixed models to examine each cortisol index in relation to infant RSAc and investigated sex differences using cross-product terms. Diurnal cortisol indices were not associated with RSAc . There was no association between hair cortisol and baseline RSAc . However, hair cortisol was associated with sex-specific changes in RSAc over the SFP-R such that, among girls, parasympathetic withdrawal was reduced with increasing prenatal exposure to cortisol. Consistently higher levels of prenatal cortisol exposure may lead to dampened parasympathetic responsivity to stress during infancy, particularly among girls. Maternal hair cortisol may be particularly valuable for studying the effects of prenatal cortisol exposure on infant autonomic reactivity.


Assuntos
Hidrocortisona , Efeitos Tardios da Exposição Pré-Natal , Feminino , Humanos , Sistema Hipotálamo-Hipofisário , Lactente , Masculino , Mães , Sistema Hipófise-Suprarrenal , Gravidez , Saliva , Estresse Psicológico
8.
Int J Mol Sci ; 22(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34298930

RESUMO

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a growing global health problem. NAFLD progression involves a complex interplay of imbalanced inflammatory cell populations and inflammatory signals such as reactive oxygen species and cytokines. These signals can derive from the liver itself but also from adipose tissue or be mediated via changes in the gut microbiome. We analyzed the effects of a simultaneous migration blockade caused by L-selectin-deficiency and an enhancement of the anti-oxidative stress response triggered by hepatocytic Kelch-like ECH-associated protein 1 (Keap1) deletion on NAFLD progression. (2) Methods: L-selectin-deficient mice (Lsel-/-Keap1flx/flx) and littermates with selective hepatic Keap1 deletion (Lsel-/-Keap1Δhepa) were compared in a 24-week Western-style diet (WD) model. (3) Results: Lsel-/-Keap1Δhepa mice exhibited increased expression of erythroid 2-related factor 2 (Nrf2) target genes in the liver, decreased body weight, reduced epidydimal white adipose tissue with decreased immune cell frequencies, and improved glucose response when compared to their Lsel-/-Keap1flx/flx littermates. Although WD feeding caused drastic changes in fecal microbiota profiles with decreased microbial diversity, no genotype-dependent shifts were observed. (4) Conclusions: Upregulation of the anti-oxidative stress response improves metabolic changes in L-selectin-deficient mice but does not prevent NAFLD progression and shifts in the gut microbiota.


Assuntos
Fezes/microbiologia , Selectina L/genética , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/genética , Regulação para Cima/genética , Animais , Dieta Ocidental , Microbioma Gastrointestinal/genética , Hepatócitos/metabolismo , Hepatócitos/patologia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/genética
9.
Psychosom Med ; 82(4): 377-383, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32176193

RESUMO

OBJECTIVE: Most of the research on vasovagal reactions has focused on the contributions of cardiovascular activity to the development of symptoms. However, other research suggests that additional mechanisms like hyperventilation may contribute to the process. The goal of the present investigation was to examine the influences of cardiovascular and respiratory variables on vasovagal symptoms. METHODS: This study was part of a randomized controlled trial investigating the effects of behavioral techniques on the prevention of vasovagal reactions in blood donors. Data from the no-treatment control group were analyzed. The final sample was composed of 160 college and university students. Observational and self-report measures of symptoms were obtained. Physiological variables were measured mainly using respiratory capnometry. RESULTS: Although respiration rate remained stable throughout donation, change in end-tidal carbon dioxide was associated with requiring treatment for a reaction during donation (odds ratio = 0.57, 95% confidence interval [CI] = 0.41 to 0.79, p = .001) and self-reported symptoms measured in the postdonation period using the Blood Donation Reactions Inventory (ß = -0.152, 95% CI = -0.28 to -0.02, t = -2.32, p = .022). Individuals with higher levels of predonation anxiety displayed larger decreases in end-tidal carbon dioxide throughout the procedure (F(2,236) = 3.64, p = .043, ηp = 0.030). Blood Donation Reactions Inventory scores were related to changes in systolic (ß = -0.022, 95% CI = -0.04 to -0.004, t = -2.39, p = .019) and diastolic blood pressure (ß = -0.038, 95% CI = -0.06 to -0.02, t = -4.03, p < .001). CONCLUSIONS: Although the vasovagal reaction has traditionally been viewed as a primarily cardiovascular event, the present results suggest that hyperventilation also plays a role in the development of vasovagal symptoms.


Assuntos
Doadores de Sangue , Hiperventilação/fisiopatologia , Síncope Vasovagal/fisiopatologia , Adulto , Ansiedade , Pressão Sanguínea/fisiologia , Sistema Cardiovascular/fisiopatologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Taxa Respiratória , Adulto Jovem
10.
Carcinogenesis ; 40(8): 947-955, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-30805627

RESUMO

Surgical resection represents the only potentially curative therapy for patients with pancreatic adenocarcinoma (PDAC), an aggressive malignancy with a very limited 5-year survival rate. However, even after complete tumor resection, many patients are still facing an unfavorable prognosis underlining the need for better preoperative stratification algorithms. Here, we explored the role of the secreted glycoprotein soluble urokinase plasminogen activator receptor (suPAR) as a novel circulating biomarker for patients undergoing resection of PDAC. Serum levels of suPAR were measured by enzyme-linked immunosorbent assay (ELISA) in an exploratory as well as a validation cohort comprising a total of 127 PDAC patients and 75 healthy controls. Correlating with a cytoplasmic immunohistochemical expression of uPAR in PDAC tumor cells, serum levels of suPAR were significantly elevated in PDAC patients compared to healthy controls and patient with PDAC precursor lesions. Importantly, patients with high preoperative suPAR levels above a calculated cutoff value of 5.956 ng/ml showed a significantly reduced overall survival after tumor resection. The prognostic role of suPAR was further corroborated by uni- and multivariate Cox-regression analyses including parameters of systemic inflammation, liver and kidney function as well as clinico-pathological patients' characteristics. Moreover, high baseline suPAR levels identified those patients particularly susceptible to acute kidney injury and surgical complications after surgery. In conclusion, our data suggest that circulating suPAR represents a novel prognostic marker in PDAC patients undergoing tumor resection that might be a useful addition to existing preoperative stratification algorithms for identifying patients that particularly benefit from extended tumor resection.


Assuntos
Adenocarcinoma/sangue , Inflamação/sangue , Neoplasias Pancreáticas/sangue , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Inflamação/genética , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Modelos de Riscos Proporcionais
11.
Transfusion ; 59(2): 566-573, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30488957

RESUMO

BACKGROUND: Whether produced by breathing too fast or too deeply, hyperventilation is common in stressful situations and may contribute to blood donation-related vasovagal symptoms. The effects of some previously tested interventions for vasovagal symptoms, for example, applied tension (AT), may be related to reduction of hyperventilation. More targeted breathing techniques might be useful. STUDY DESIGN AND METHODS: This was a randomized controlled trial comparing the effects of AT, a slow, shallow "anti-hyperventilation" breathing technique previously tested in phobic individuals (respiration control [RESP]), the combination of AT and RESP, and no intervention on blood donors participating in university clinics. A total of 547 eligible donors were assigned randomly to one of these four groups. Observational, self-report, and physiologic measures (primarily via respiratory capnometry) were obtained. RESULTS: Although both RESP and AT had some positive impact on blood donation outcome, the effects of RESP were more numerous, albeit limited primarily to donors who had less general fear of medical procedures. For example, lower-fear donors assigned to practice RESP had significantly lower Blood Donation Reaction Inventory scores and were significantly less likely to require treatment for symptoms than no-treatment individuals. In general, RESP led to a significant decrease in respiration rate, though it did not influence end-tidal CO2 , a more precise measure of hyperventilation. CONCLUSION: While the mechanisms remain somewhat unclear and the interventions did not benefit more fearful, higher-risk donors, respiration control is a promising additional approach to reducing vasovagal symptoms.


Assuntos
Doadores de Sangue , Exercícios Respiratórios , Taxa Respiratória , Síncope Vasovagal , Adulto , Feminino , Humanos , Masculino , Síncope Vasovagal/etiologia , Síncope Vasovagal/fisiopatologia , Síncope Vasovagal/prevenção & controle
12.
Respirology ; 24(1): 48-54, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30003637

RESUMO

BACKGROUND AND OBJECTIVE: Prevention of exacerbations in chronic obstructive pulmonary disease (COPD) is important to decrease overall declines in functioning and improve quality of life. The present study sought to develop a psychometrically valid measure of perceived triggers of exacerbations in COPD patients, the COPD Exacerbation Trigger Inventory (CETI). METHODS: Participants (n = 192) were recruited through local clinics and online to complete surveys of the CETI, demographic information, disease-specific information and the COPD Assessment Test (CAT). The CETI included a free response section on patients' individual top triggers, combined with ratings of their controllability. RESULTS: Exploratory principal component analyses identified a stable 5-factor structure (33 items), from which trigger subscales for weather/climate, air pollution/irritants, exercise, infection/illness and psychological factors were formed (internal consistency Cronbach's α = 0.90-0.94). Trigger factors were associated with COPD functional status, exacerbation frequency and healthcare utilization. Participants found personal triggers related to dust, air pollution, smoking and physical activity to be the most easily controlled, whereas those related to psychological factors, climate, infection, respiratory symptoms and sleep to be more difficult to control. Greater perceived controllability of triggers was associated with lower CAT scores, indicating better health status and less impact of the disease on functioning. CONCLUSION: The CETI is a psychometrically valid measure of perceived exacerbation triggers in patients with COPD. Perceived triggers are associated with clinical outcomes. Assessment of trigger classes and their controllability may prove useful in both research and clinical settings with COPD patients and to further our knowledge in prevention and disease management.


Assuntos
Causalidade , Autoavaliação Diagnóstica , Psicometria/métodos , Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Inquéritos e Questionários , Exacerbação dos Sintomas , Idoso , Feminino , Disparidades nos Níveis de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Serviços Preventivos de Saúde/métodos , Prognóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/psicologia , Reprodutibilidade dos Testes
13.
Cell Immunol ; 330: 175-182, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29454647

RESUMO

Liver macrophages attract increasing interest due to their crucial roles in homeostasis and hepatic diseases. Recent findings in mice and man suggest a remarkable phenotypic and functional diversity of liver macrophages. Kupffer cells, the subset of tissue resident macrophages with sentinel functions in liver, mainly arise from embryogenic precursors, whereas in injury, liver tissue is engrafted by monocyte-derived macrophages. Both principal macrophage populations respond to local or systemic signals and have substantial effects on reduction as well as aggravation of hepatic diseases. Despite contrasting functions of heterogeneous macrophage subsets in disease progression and regression, they may provide promising targets for novel therapeutic interventions in hepatology. Areas of intense research include their multifaceted roles in metabolic diseases (non-alcoholic steatohepatitis, NASH), fibrosis or liver cancer (hepatocellular or cholangiocellular carcinoma, HCC or CCA). We discuss recent findings on the origin, diversity and functional plasticity of liver macrophages in homeostasis and hepatic disease conditions.


Assuntos
Plasticidade Celular/imunologia , Homeostase/imunologia , Fígado/imunologia , Macrófagos/imunologia , Animais , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Humanos , Fígado/citologia , Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/patologia
14.
BMC Med Res Methodol ; 18(1): 18, 2018 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-29409461

RESUMO

BACKGROUND: Demands placed on individuals in occupational and social settings, as well as imbalances in personal traits and resources, can lead to chronic stress. The Trier Inventory for Chronic Stress (TICS) measures chronic stress while incorporating domain-specific aspects, and has been found to be a highly reliable and valid research tool. The aims of the present study were to confirm the German version TICS factorial structure in an English translation of the instrument (TICS-E) and to report its psychometric properties. METHODS: A random route sample of healthy participants (N = 483) aged 18-30 years completed the TICS-E. The robust maximum likelihood estimation with a mean-adjusted chi-square test statistic was applied due to the sample's significant deviation from the multivariate normal distribution. Goodness of fit, absolute model fit, and relative model fit were assessed by means of the root mean square error of approximation (RMSEA), the Comparative Fit Index (CFI) and the Tucker Lewis Index (TLI). RESULTS: Reliability estimates (Cronbach's α and adjusted split-half reliability) ranged from .84 to .92. Item-scale correlations ranged from .50 to .85. Measures of fit showed values of .052 for RMSEA (Cl = 0.50-.054) and .067 for SRMR for absolute model fit, and values of .846 (TLI) and .855 (CFI) for relative model-fit. Factor loadings ranged from .55 to .91. CONCLUSION: The psychometric properties and factor structure of the TICS-E are comparable to the German version of the TICS. The instrument therefore meets quality standards for an adequate measurement of chronic stress.


Assuntos
Análise Fatorial , Psicometria/métodos , Estresse Psicológico/diagnóstico , Inquéritos e Questionários/normas , Adolescente , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Estresse Psicológico/psicologia , Adulto Jovem
15.
J Behav Med ; 41(6): 771-783, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29679183

RESUMO

Fear of blood and needles increases risk for presyncopal symptoms. Applied muscle tension can prevent or attenuate presyncopal symptoms; however, it is not universally effective. This study examined the effects of applied muscle tension, a respiratory intervention, and a no treatment control condition, on presyncopal symptoms and cerebral oxygenation, during a simulated blood draw with individuals highly fearful of needles. Participants (n = 95) completed questionnaires, physiological monitoring, and two trials of a simulated blood draw with recovery. Presyncopal symptoms decreased across trials; however, no group differences emerged. Applied muscle tension was associated with greater cerebral oxygenation during trial two, and greater end-tidal carbon dioxide during both trials. The respiratory intervention did not differ from the no treatment control. Applied muscle tension is an intervention that can increase cerebral oxygenation and end-tidal carbon dioxide. While the respiratory intervention is promising within therapeutic settings, it was not efficacious after a brief audio training.


Assuntos
Ansiedade/prevenção & controle , Medo/psicologia , Tono Muscular , Transtornos Fóbicos/prevenção & controle , Adulto , Ansiedade/psicologia , Doadores de Sangue/psicologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Agulhas/efeitos adversos , Transtornos Fóbicos/psicologia , Inquéritos e Questionários , Síncope/prevenção & controle
16.
Am J Physiol Regul Integr Comp Physiol ; 312(6): R1004-R1016, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28381457

RESUMO

Calcium-binding protein spermatid-specific 1 (CABS1) is expressed in the human submandibular gland and has an anti-inflammatory motif similar to that in submandibular rat 1 in rats. Here, we investigate CABS1 in human saliva and its association with psychological and physiological distress and inflammation in humans. Volunteers participated across three studies: 1) weekly baseline measures; 2) a psychosocial speech and mental arithmetic stressor under evaluative threat; and 3) during academic exam stress. Salivary samples were analyzed for CABS1 and cortisol. Additional measures included questionnaires of perceived stress and negative affect; exhaled nitric oxide; respiration and cardiac activity; lung function; and salivary and nasal inflammatory markers. We identified a CABS1 immunoreactive band at 27 kDa in all participants and additional molecular mass forms in some participants. One week temporal stability of the 27-kDa band was satisfactory (test-retest reliability estimate = 0.62-0.86). Acute stress increased intensity of 18, 27, and 55 kDa bands; 27-kDa increases were associated with more negative affect and lower heart rate, sympathetic activity, respiration rate, and minute ventilation. In both acute and academic stress, changes in 27 kDa were positively associated with salivary cortisol. The 27-kDa band was also positively associated with VEGF and salivary leukotriene B4 levels. Participants with low molecular weight CABS1 bands showed reduced habitual stress and negative affect in response to acute stress. CABS1 is readily detected in human saliva and is associated with psychological and physiological indicators of stress. The role of CABS1 in inflammatory processes, stress, and stress resilience requires careful study.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Saliva/metabolismo , Estresse Psicológico/metabolismo , Adolescente , Adulto , Afeto , Asma/metabolismo , Asma/fisiopatologia , Asma/psicologia , Biomarcadores/metabolismo , Feminino , Volume Expiratório Forçado , Frequência Cardíaca , Humanos , Hidrocortisona/metabolismo , Leucotrieno B4/metabolismo , Masculino , Conceitos Matemáticos , Pessoa de Meia-Idade , Peso Molecular , Taxa Respiratória , Fala , Estresse Psicológico/etiologia , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Fatores de Tempo , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem
17.
Depress Anxiety ; 34(12): 1096-1105, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28294471

RESUMO

BACKGROUND: Blood injection injury (BII) phobia is common, with debilitating consequences to the health and well being of many of its sufferers. BII phobia presents with a unique fear response that can involve drops in blood pressure and ultimately fainting. The aim of this study was to provide proof of concept for a line of brief, easy to implement, video-based interventions for reducing phobic avoidance and fears in BII sufferers. One of the interventions was a novel Hypoventilation Respiratory Training (HRT) aimed at reducing the exaggerated ventilation response (hyperventilation) seen in BII phobia. The response has been linked to cerebral vasoconstriction and fainting symptoms. METHOD: Sixty BII patients were randomly assigned to one of three 12-min video-guided trainings: Symptom-Associated Tension (SAT) training, Relaxation Skills Training (RST), or HRT. Experiential and cardiorespiratory activity to phobic stimuli was assessed before and after training. RESULTS: Both SAT and HRT resulted in overall greater reductions of phobic fears and symptoms than RST. SAT significantly increased heart rate during exposure, and HRT led to significantly reduced ventilation, increases in PCO2 , and elevated blood pressure throughout exposure and recovery. Treatment expectancy was rated equally high across conditions, whereas credibility ratings were highest for HRT. CONCLUSIONS: Brief, video-based instructions in muscle tension and normocapnic breathing are effective in reducing BII symptom severity and require minimal time and expertise. HRT may be particularly helpful in reducing fainting caused by cerebral vasoconstriction.


Assuntos
Terapia Comportamental/métodos , Injeções , Transtornos Fóbicos/terapia , Síncope/prevenção & controle , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Fóbicos/complicações , Síncope/etiologia , Adulto Jovem
18.
Annu Rev Clin Psychol ; 13: 209-240, 2017 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-28375724

RESUMO

Panic disorder (PD) is unique among the anxiety disorders in that panic symptoms are primarily of a physical nature. Consequently, comorbidity with medical illness is significant. This review examines the association between PD and medical illness. We identify shared pathophysiological and psychological correlates and illustrate how physiological activation in panic sufferers underlies their symptom experience in the context of the fight-or-flight response and beyond a situation-specific response pattern. We then review evidence for bodily symptom perception accuracy in PD. Prevalence of comorbidity for PD and medical illness is presented, with a focus on respiratory and cardiovascular illness, irritable bowel syndrome, and diabetes, followed by an outline for potential pathways of a bidirectional association. We conclude by illustrating commonalities in mediating mechanistic pathways and moderating risk factors across medical illnesses, and we discuss implications for diagnosis and treatment of both types of conditions.


Assuntos
Doenças Cardiovasculares , Comorbidade , Diabetes Mellitus , Interocepção/fisiologia , Síndrome do Intestino Irritável , Transtorno de Pânico , Transtornos Respiratórios , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Humanos , Síndrome do Intestino Irritável/epidemiologia , Transtorno de Pânico/epidemiologia , Transtorno de Pânico/fisiopatologia , Transtornos Respiratórios/epidemiologia
19.
Stress ; 19(1): 45-52, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26551892

RESUMO

We examined whether lifetime exposure to stressful and traumatic events alters hypothalamic-pituitary-adrenal (HPA) axis functioning, as indexed by hair cortisol, regardless of associated psychopathology, among pregnant women of different racial/ethnic backgrounds. 180 women provided hair samples for measurement of integrated cortisol levels throughout pregnancy and information regarding their lifetime exposure to stressful and traumatic life events. Results indicate that increased lifetime exposure to traumatic events was associated with significantly greater hair cortisol over the course of pregnancy. Similarly, greater lifetime exposure to stressful and traumatic events weighted by reported negative impact (over the previous 12 months) was associated with significantly greater hair cortisol during pregnancy. All analyses controlled for maternal age, education, body mass index (BMI), use of inhaled corticosteroids, race/ethnicity, and post-traumatic stress disorder (PTSD) and depressive symptoms. Following stratification by race/ethnicity, associations between stressful and traumatic life events and hair cortisol were found among Black women only. This is the first study to consider associations between lifetime stress exposures and hair cortisol in a sociodemographically diverse sample of pregnant women. Increased exposure to stressful and traumatic events, independent of PTSD and depressive symptoms, was associated with higher cortisol production, particularly in Black women. Future research should investigate the influence of such increased cortisol exposure on developmental outcomes among offspring.


Assuntos
Depressão/metabolismo , Etnicidade/estatística & dados numéricos , Acontecimentos que Mudam a Vida , Gestantes , Trauma Psicológico/metabolismo , Transtornos de Estresse Pós-Traumáticos/metabolismo , Adulto , Negro ou Afro-Americano , Estudos de Coortes , Depressão/epidemiologia , Depressão/psicologia , Feminino , Cabelo/química , Hispânico ou Latino , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez , Estudos Prospectivos , Trauma Psicológico/epidemiologia , Trauma Psicológico/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Estados Unidos/epidemiologia , População Branca , Adulto Jovem
20.
Depress Anxiety ; 33(10): 927-938, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27699943

RESUMO

Anhedonia, or loss of interest or pleasure in usual activities, is characteristic of depression, some types of anxiety, as well as substance abuse and schizophrenia. Anhedonia is a predictor of poor long-term outcomes, including suicide, and poor treatment response. Because extant psychological and pharmacological treatments are relatively ineffective for anhedonia, there is an unmet therapeutic need for this high-risk symptom. Current psychological and drug treatments for anxiety and depression focus largely on reducing excesses in negative affect rather than improving deficits in positive affect. Recent advances in affective neuroscience posit that anhedonia is associated with deficits in the appetitive reward system, specifically the anticipation, consumption, and learning of reward. In this paper, we review the evidence for positive affect as a symptom cluster, and its neural underpinnings, and introduce a novel psychological treatment for anxiety and depression that targets appetitive responding. First, we review anhedonia in relation to positive and negative valence systems and current treatment approaches. Second, we discuss the evidence linking anhedonia to biological, experiential, and behavioral deficits in the reward subsystems. Third, we describe the therapeutic approach for Positive Affect Treatment (PAT), an intervention designed to specifically target deficits in reward sensitivity.


Assuntos
Anedonia/fisiologia , Antecipação Psicológica/fisiologia , Transtornos de Ansiedade/fisiopatologia , Transtornos de Ansiedade/terapia , Comportamento Apetitivo/fisiologia , Encéfalo/fisiopatologia , Transtorno Depressivo/fisiopatologia , Transtorno Depressivo/terapia , Psicoterapia/métodos , Afeto/fisiologia , Humanos , Motivação , Recompensa
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