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The combination of radiotherapy (RT) with immunotherapy represents a promising treatment modality for non-small cell lung cancer (NSCLC) patients. As only a minority of patients shows a persistent response today, a spacious optimization window remains to be explored. Previously we showed that fractionated RT can induce a local immunosuppressive profile. Based on the evolving concept of an immunomodulatory role for vagal nerve stimulation (VNS), we tested its therapeutic and immunological effects alone and in combination with fractionated RT in a preclinical-translational study. Lewis lung carcinoma-bearing C57Bl/6 mice were treated with VNS, fractionated RT or the combination while a patient cohort with locally advanced NSCLC receiving concurrent radiochemotherapy (ccRTCT) was enrolled in a clinical trial to receive either sham or effective VNS daily during their 6 weeks of ccRTCT treatment. Preclinically, VNS alone or with RT showed no therapeutic effect yet VNS alone significantly enhanced the activation profile of intratumoral CD8+ T cells by upregulating their IFN-γ and CD137 expression. In the periphery, VNS reduced the RT-mediated rise of splenic, but not blood-derived, regulatory T cells (Treg) and monocytes. In accordance, the serological levels of protumoral CXCL5 next to two Treg-attracting chemokines CCL1 and CCL22 were reduced upon VNS monotherapy. In line with our preclinical findings on the lack of immunological changes in blood circulating immune cells upon VNS, immune monitoring of the peripheral blood of VNS treated NSCLC patients (n=7) did not show any significant changes compared to ccRTCT alone. As our preclinical data do suggest that VNS intensifies the stimulatory profile of the tumor infiltrated CD8+ T cells, this favors further research into non-invasive VNS to optimize current response rates to RT-immunotherapy in lung cancer patients.

Post-operative pain is a common clinical problem after surgery, yet its predictors are inconsistent and unclear. This study examined whether pre-surgical vagal cardiac efferent nerve activity, indirectly indexed by heart rate variability (HRV), predicts patients' pain after epileptic surgery.Using a prospective design, HRV was measured at rest during 5 min in n = 30 patients, prior to undergoing epileptic surgery. Post-operative pain was assessed every 8 h during the first 2 days after surgery, and our analyses focused on the worse pain level. We used multiple regression analyses and statistically considered several confounders (age, surgical duration, and analgesics during various surgical phases).Multiple HRV indexes strongly and inversely predicted post-operative pain, with high-frequency HRV (HF-HRV) being the strongest predictor (r = -0.81, p 0.001). In a hierarchical multiple regression, HF-HRV accounted for an additional and significant 18% of the variance in post-operative pain, after statistically considering effects of age, surgical duration and effects of two anaesthetics.Pre-surgical HF-HRV independently, strongly and inversely predicts post-operative pain. These results are in line with a neuromodulatory role of the vagus nerve in pain and have clinical implications for predicting and managing post-operative pain.

This chapter discusses the clinical and empirical perspectives concerning adherence to treatment in hypertension (HT) and coronary heart disease (CHD). The correlates of adherence may be divided into treatment-related, disease-related, physician-related, patient background and patient trait/state or psychosocial variables. While the main challenge of adherence in HT is ensuring that prescribed medication is taken, this is only one of several challenges for CHD patients. The comprehensiveness of assessing adherence in CHD follows the complexity of its medical treatment. The Medical Outcomes Study assessed adherence to specific behaviours recommended to patients with heart disease in the same way they did for patients with HT. The Minnesota Heart Health Program aimed at increasing awareness and adherence to smoking cessation, preventing HT, reducing salt, fat and alcohol consumption, and increasing physical exercise for preventing CHD at the community of Mankato, Minnesota and USA.

BackgroundHeart Rate Variability (HRV) represents efferent vagus nerve activity which is suggested to be inversely related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various types of cancer. HRV is also believed to predict the occurrence and severity of post-operative complications. We aimed to determine the role of pre-operative HRV as a prognostic factor in overall and cancer free survival in patients with colorectal cancer.MethodsRetrospective analysis was performed in a detailed dataset of patients diagnosed with primary colorectal cancer between January 2010 and December 2016, who underwent curative surgical treatment. HRV was measured as time-domain parameters (SDNN (Standard Deviation of NN-intervals) and RMSSD (Root Mean Square of Successive Differences)) based on pre-operative 10 second ECGs. Groups were created by baseline HRV: Low HRV (SDNN ResultsA total of 428 patients were included in this study. HRV was not significantly associated with overall survival (SDNN ConclusionsHeart rate variability was not associated with overall or cancer free survival in patients with primary colorectal cancer who underwent curative surgical treatment. These results do not align with results found in studies including only patients with advanced cancer, which suggests that there is only an association in the other direction, cancer causing low HRV.

Little is known about the interplay between the autonomic nervous system and disease activity in multiple sclerosis (MS). We examined the relationship between heart rate variability (HRV), a reliable measure of vagal nerve function, and disease characteristics in a prospective MS cohort. Standard deviation of each normal-to-normal inter-beat interval (SDNN) and root mean square of successive differences (RMSSD), global indices of HRV, were measured in 114 MS patients, which included four predefined subgroups, and 30 age and sex-matched healthy controls (HC). We assessed group differences at baseline, HRV reproducibility at month 3, and used logistic regression modeling to relate baseline HRV with relapse occurrence. No significant HRV differences were found between MS and HC and between MS subgroups. In MS patients, both HRV indices correlated with age (r = &minus, 0.278, p = 0.018 and r = &minus, 0.319, p &lt, 0.001, respectively) and with month 3 assessments (r = 0.695 and r = 0.760, p &lt, 0.001). Higher SDNN and RMSSD at baseline were associated with self-reported relapses at month 3 (OR = 1.053, 95% CI (1.013&ndash, 1.095), p = 0.009 and OR = 1.065, 95% CI (1.016&ndash, 1.117), p = 0.009), and SDNN at baseline with relapses at month 12 (OR = 1.034, 95% CI (1.009&ndash, 1.059), p = 0.008, ROC, AUC = 0.733, p = 0.002). There were no baseline HRV differences between MS and HC or between subgroups. Post-hoc analysis showed an association with an increased relapse risk.

Accumulating evidence points to a beneficial effect ofvagus nerve activity in tumor development. The vagus nerve is proposed to slow tumorigenesis because of its anti-inflammatory properties mediated through ACh and the α7nAChR. Since α7nAChRs are widely expressed by many types of immune cells we hypothesized that the vagus nerve affects the tumor microenvironment and anticancer immunity. We found direct evidence in studies using animal cancer models that vagus nerve stimulation alters immunological responses relevant to the tumor microenvironment. Also studies in pathologies other than cancer suggest a role for the vagus nerve in altering immunological responses relevant to anticancer immunity. These results provide a rationale to expect that vagus nerve stimulation, in combination with conventional cancer treatments, may improve the prognosis of cancer patients by promoting anticancer immunity.

‘Mind–body’ debates assume that better brain–body associations are healthy. This study examined whether degree of associations between a neurophysiological vagal nerve index and peripheral disease biomarkers predict prognosis in pancreatic cancer (PC) and multiple sclerosis (MS). Sample 1 included 272 patients with advanced PC. Sample 2 included 118 patients with MS. We measured the vagal nerve index heart rate variability (HRV) derived from electrocardiograms. We examined associations between HRV and patients’ peripheral disease biomarkers: CA19-9 in PC and neurofilament light chain (NFL) in MS. Associations between HRV and each biomarker were examined separately in patients who survived or died (PC), and in those with and without relapse during 12 months (MS). In PC, HRV was significantly inversely related to the tumor marker CA19-9 in patients who later survived (r = −0.44, p < 0.05) but not in those who died (r = 0.10, NS). In MS, HRV was significantly and inversely related to NFL only in those who did not relapse (r = −0.25, p < 0.05), but not in those who relapsed (r = −0.05, NS). The degree of association between a neurophysiological vagal marker and peripheral disease biomarkers has prognostic value in two distinct diseases.

One of the challenges facing researchers in the domain of human immunodeficiency virus prevention is the assessment of condom use in an unbiased self-reported manner. The current study presents the development and preliminary validation of an indirect condom use test (I-CUTE), designed to assess condom use tendencies and to overcome self-report biases. Two samples were included using correlational designs. In sample 1, 88 students from European university completed the I-CUTE with questionnaires of condom use barriers, social desirability, and condom use negotiation self-efficacy. In sample 2, 212 students from sub-Saharan universities completed the I-CUTE with questionnaires of condom use barriers and knowledge. The I-CUTE included 17 pictures of human figures in relation to condom use, where participants had to choose one of the four a-priori given sentences reflecting the figures’ thoughts. This represented a semi-projective, yet standardized test. In sample 1, I-CUTE scores were inversely related to barriers, positively correlated with condom use negotiation self-efficacy and unrelated to social desirability. In sample 2, I-CUTE scores were inversely related to barriers and unrelated to knowledge scores. In a multiple regression, condom use barriers had a unique contribution to explaining variance in I-CUTE scores, beyond the contribution of background variables and knowledge. These results support the preliminary reliability and validity of the I-CUTE tool in a variety of cultures, and reveal its lack of bias by social desirability and the importance of condom use barriers in condom use tendencies.Keywords: condom use, barriers, social desirability, assessment, measure

International audience; No abstract available

The chapter begins by a hypothetical case and an introduction to biomedical risk factors and the etiology of coronary heart disease (CHD). We then review psychosocial etiological risk factors and psychosocial prognostic factors of CHD (e.g., hostility, depression, Type-D personality). The chapter then presents in depth the PNI of the acute coronary syndrome with an emphasis on the vagal nerve and inflammation. We then discuss behavioral mediators between psychological factors and CHD prognosis and the evidence for the effects of various psychological interventions on CHD prognosis. These are done via meta-analyses and specific studies. The chapter ends with returning to the hypothetical case, vis-a-vis the presented studies.

This chapter presents one of the topics which involves behavioral medicine, clinical psychology, and psychiatry, namely, emergency mental health. The chapter also reveals the heavy psychological and societal price we pay when not performing evidence-based interventions. After presenting the chapter’s “case,” theoretical models, explaining responses to traumatic events, are presented. Risk factors for developing PTSD after traumatic events are described, based on scientific literature. I then review evidence concerning past interventions for preventing PTSD, with particular emphasis on the failure of debriefing. This is followed by a voyage into the neuropsychology of trauma leading to an alternative intervention, the memory structuring intervention (MSI), which is a neuroscience-based and evidence-based intervention. Additional methods in emergency mental health are mentioned, and the chapter ends by “treating” better our hypothetical case.

This is the second chapter on a specific population, namely, the elderly. After presenting the hypothetical “case,” the chapter briefly reviews basic biological processes in aging. Psychological models in gerontology are mentioned, including the less known model of gerotranscendence. Stress and the importance of control and perceived control in the elderly are reviewed in depth as a central psychological aspect of aging with pivotal health implications. Psychological aspects of dementia are then discussed, followed by psychological aspects of falling in the elderly. Here, a psychobiological model of this issue is proposed, which includes environmental, psychosocial, and biological components. We then learn several PNI aspects of psychogeriatrics and examine effects of psychological interventions in the elderly. The chapter ends by returning to its case and “treating” it better, vis-a-vis the reviewed empirical evidence. This chapter is of high relevance to the current aging population, worldwide.

Background: Myofascial trigger points (MTrPs) are common in people with musculoskeletal pain and may play a role in chronic nonspecific low back pain (CLBP). One of the potential treatments of MTrPs is the Nervomatrix Soleve® auto-targeted neurostimulation device, providing targeted transcutaneous electrical nerve stimulation (TENS) to MTrPs in the lower back muscles. To date, no controlled studies have evaluated the effectiveness of this device for the pain management of this population. Objective: To examine whether the Nervomatrix Soleve® auto-targeted neurostimulation device is superior over placebo for the treatment of CLBP. Study Design: A fourfold-blind randomized controlled trial was conducted. Setting: Brussels University Hospital, health care centers and pharmacies around Belgium. Methods: Participants with CLBP for at least 3 months were randomly assigned to the experimental (the Nervomatrix Soleve® auto-targeted neurostimulation device providing TENS-stimulation and mechanical pressure) or placebo group (the Nervomatrix Soleve® autotargeted neurostimulation device providing mechanical pressure alone without current). The treatment protocol in both groups consisted of 6 treatment sessions per patient. Participants were evaluated at baseline prior to the intervention, immediately following treatment, and at one month follow-up. Pain and pain behavior (steps climbed) were assessed as primary outcome measures. Secondary outcome measures were pain functioning, health beliefs, symptoms of central sensitization, pain catastrophizing, and kinesiophobia. Results: In total, 39 participants were included in the study. Participants in both groups improved significantly for pain and functioning, but no significant differences were observed between groups. These improvements were not clinically meaningful for any of the reported measures. The health beliefs changed significantly in both groups (P < 0.05), with superior results at follow-up in the placebo group. Limitations: The follow-up period is limited to one month. Conclusions: Treatment of MTrPs with the Nervomatrix Soleve® auto-targeted neurostimulation device in patients with CLBP does not result in a better outcome than placebo-treatment in terms of pain, pain behavior, functioning, central sensitization, pain catastrophizing, and health beliefs. Key words: Low back pain, chronic pain, randomized controlled trial, electric stimulation therapy, trigger points

Psychosocial factors have been linked to cardiovascular diseases independently of traditional risk factors. The impact of psychosocial factors on plaque destabilizing factors, such as matrix metalloproteinases (MMPs) has been proposed although scarcely studied. Objective: To evaluate the relationships between hostility, perceived stress and social support with MMPs activity in patients after an Acute Myocardial Infarction (AMI). Methods: Blood samples were obtained from 76 patients on admission, post-angioplasty, 24. h, 7 days and 3 months after AMI. Hostility, perceived stress and social support were evaluated by validated questionnaires. Results: Social support was positively correlated with patientś ejection fraction (r = 0.453, p = 0.009). Patients with higher infarct size presented increased MMP-2 activity at admission (p = 0.04). Patients with one diseased vessel had more social support than those with three diseased vessels (p = 0.05). The highest values of MMP-2 and MMP-9 activity were observed at the acute event, decreasing, with the lowest activity at 3 months post-AMI (p < 0.001). Only in patients with low social support, hostility correlated with MMP-2 activity, from AMI onset (r = 0.645, p = 0.013), to 7 days post AMI (r = 0.557, p = 0.038). Hostility explained up to 28% of the variance in MMP-2 activity (R2=0.28, p = 0.005). Finally, in patients with high hostility, MMP-9 was positively correlated with IL-1β (r = 0.468, p = 0.02). Conclusions: This study adds weight to the idea that two psychosocial factors, namely hostility and social support, acting jointly, may affect MMP-2 activity. Moreover, in hostile patients, there is a link between IL-1β and MMP-9. These findings support the role of psychosocial factors in plaque destabilization and in the inflammatory process in AMI. Fil: Fernandez Machulsky, Nahuel Hernan. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina Fil: Fabre, Bibiana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Miksztowicz, Verónica Julieta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Lombardo, Micaela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: García Escudero, Alejandro. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina Fil: Gigena, Gerardo. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina Fil: Blanco, Federico Carlos. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina Fil: Gelpi, Ricardo Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Schreier, Laura Ester. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina Fil: Gidron, Yori. Vrije Unviversiteit Brussel; Bélgica Fil: Berg, Gabriela Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina

Made available in DSpace on 2022-04-29T08:45:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-10-01 Aim: To compare cardiac autonomic modulation in early- versus advanced-stage breast cancer patients before any type of cancer treatment and investigate associated factors. Methods and results: This cross-sectional study included women (30–69 years old) with primary diagnosis of breast cancer and women with benign breast tumors. We evaluated cardiac modulation by heart rate variability and assessed factors of anxiety, depression, physical activity, and other relevant medical variables. Patients were divided into three groups based on TNM staging of cancer severity: early-stage cancer (n = 42), advanced-stage cancer (n = 37), or benign breast tumors to serve as a control (n = 37). We analyzed heart rate variability in time and frequency domains. The advanced-stage cancer group had lower vagal modulation than early-stage and benign groups; also, the advance-stage group had lower overall heart rate variability when compared to benign conditions. Heart rate variability was influenced by age, menopausal status, and BMI. Conclusions: Heart rate variability seems to be a promising, non-invasive tool for early diagnosis of autonomic dysfunction in breast cancer and detection of cardiovascular impairments at cancer diagnosis. Cardiac autonomic modulation is inversely associated with breast cancer staging. Departamento de Medicina Disciplina de Cardiologia Hospital São Paulo Escola Paulista de Medicina Universidade Federal de São Paulo, 715 Napoleão de Barros St Departamento de Fisioterapia Faculdade de Ciência e Tecnologia Universidade do Estado de São Paulo, 305 Roberto Símonsen St Faculdade de Medicina do ABC Laboratório de Epidemiologia e Análise de Dados, 2000 Lauro Gomes Av Department of Physiology and Institute of Molecular Cardiology School of Medicine University of Louisville, Baxter Biomedical Research Building II, 590 S Preston St Instituto do Câncer Doutor Arnaldo Vieira de Carvalho, 66 Largo do Arouche Departamento de Ginecologia Hospital São Paulo Escola Paulista de Medicina Universidade Federal de São Paulo Centro de Referência da Saúde da Mulher Hospital Pérola Byington, 683 Brigadeiro Luís Antônio Ave Departamento de Medicina Disciplina de Clínica Médica Hospital São Paulo Escola Paulista de Medicina Universidade Federal de São Paulo Free University of Brussels (VUB), Boulevard de la Plaine 2

Method: We retroactively derived markers of vagal nerve activity indexed by heart rate variability (HRV), specifically the root mean square of successive differences (RMSSD), from patients' electrocardiograms near diagnosis. The NIM index was the ratio of RMSSD to C-reactive protein levels (RMSSD/CRP). Sample 1 included 202 Belgian patients with advanced pancreatic cancer (PC), while sample 2 included 71 Belgian patients with non-small cell lung cancer (NSCLC). In both samples, we examined the overall survival, while in sample 2, we additionally examined the survival time in deceased patients., SCOPUS: ar.j, info:eu-repo/semantics/published

// Dimple Y. Chudasama 1, 2 , Zeynep Aladag 2 , Mayla I. Felicien 2 , Marcia Hall 2 , Julie Beeson 1 , Nizar Asadi 1 , Yori Gidron 3 , Emmanouil Karteris 2 and Vladimir B. Anikin 1 1 Division of Thoracic Surgery, The Royal Brompton & Harefield NHS Foundation Trust, Harefield Hospital, London, UK 2 Division of Biosciences, Brunel University London, London, UK 3 Scalab, Lille University, Oncolille, Lille, France Correspondence to: Vladimir B. Anikin, email: V.Anikin@rbht.nhs.uk Keywords: circulating tumour DNA; Alu repeats; DNA integrity index; malignant lung tumours; liquid biopsy Received: August 12, 2017 Accepted: March 06, 2018 Published: April 20, 2018 ABSTRACT Introduction: Lung cancer survival remains poor in the western world due to late presentation in most cases, leading to difficulty of treatment in these advanced and metastatic patients. Therefore, the development of a robust biomarker for prognosis and to monitor treatment response and relapse would be of great benefit. The use of Alu repeats and DNA Integrity Index has been shown to hold both diagnostic and prognostic value, and as it is obtained from the plasma of patients, it can serve as a non-invasive tool for routine monitoring. This study evaluates the efficiency of this technique in malignant lung cancer patients. Methods: Plasma samples were collected from 48 patients, consisting of 29 lung cancer patients and 19 non-cancer controls. Alu repeat ratio and confounders were measured. Results: Observations showed a higher Alu repeat ratio amongst the cancer group compared to controls ( p=0.035) , mean Alu ratio 0.38 (range 0.01-0.93) and 0.22 (0.007-0.44) respectively, ROC curve analysis AUC 0.61 (p=0.22) . Analysis by staging was more promising, whereby a higher DNA Integrity Index was seen in advanced cases compared to both early stage and controls, p 0.5 to be associated with poorer overall survival p=0.03 . Conclusion: The results of this study show a potential use of Alu repeats ratios for prognostic purposes in the advanced setting for lung cancer patients.

Acute stress reactions immediately after exposure to trauma or crisis have received growing attention in recent years and are gaining momentum in light of recent mass traumatic events worldwide including conflicts, terrorist attacks and natural disasters. Unlike routine life, traumatic or emergency situations are unexpected and unstructured events. Early helping responses in these situations is of utmost importance: immediate, focused and efficient interventions are beneficial for the reduction of acute stress reactions and a return to normal functioning as well as decreasing the risk for future onset of post-traumatic stress disorder symptoms. However, many early efforts were either found to be ineffective or are based on narrative expression and empathy alone. The aim of this paper is to present the SIX Cs model - a new psychological first aid approach - immediate cognitive-functional psychological first aid - for the global nonprofessional community as well as for first responders. The model addresses the need to standardize interventions during an Acute Stress Reaction and intends to help shift the person from helplessness & passiveness into active effective functioning, within minutes, in the immediate aftermath of a perceived traumatic event. The model is based on four theoretical and empirically tested concepts: (1) Hardiness, (2) Sense of Coherence, (3) Self-Efficacy, and (4) on the Neuro-psychology of the stress response, focusing on shifting people from a limbic system hyperactivity to a prefrontal cortex activation during stressful events. Preliminary results on the effectiveness of the SIX Cs model in terms of increasing resiliency, reducing anxiety and improving perceived self-efficacy are presented. To date, this approach has been recognized by the Israeli Ministry of Health as the Israeli national model for psychological first aid.

While the parasympathetic nervous system appears to be involved in the regulation of tumor progression, its exact role is still unclear. Therefore, using a rat BP6-TU2 fibrosarcoma tumor model, we investigated the effect of (1) reduction of vagal activity produced by subdiaphragmatic vagotomy; and (2) enhancement of vagal activity produced by continuous delivery of electric impulses to the cervical part of the vagus nerve on tumor development and survival of tumor-bearing rats. We also evaluated the expression of cholinergic receptors within in vitro cultivated BP6-TU2 cells. Interestingly, we found that both, vagal stimulation and subdiaphragmatic vagotomy slightly reduced tumor incidence. However, survival of tumor-bearing rats was not affected by any of the experimental approaches. Additionally, we detected mRNA expression of the α1, α2, α5, α7, and α10 subunits of nicotinic receptors and the M1, M3, M4, and M5 subtypes of muscarinic receptors within in vitro cultivated BP6-TU2 cells. Our data indicate that the role of the vagus nerve in modulation of fibrosarcoma development is ambiguous and uncertain and requires further investigation.

OBJECTIVES: Pain is a complex common health problem, with important implications for quality of life and with huge economic consequences. Pain can be elicited due to tissue damage, as well as other multiple factors such as inflammation and oxidative stress. Can there be 1 therapeutic pathway that may target multiple etiologic factors in pain? METHODS: In the present article, we review evidence for the relationships between vagal nerve activity and pain, and between vagal nerve activity and 5 factors that are etiologic to or protective in pain. RESULTS: Vagal nerve activity inhibits inflammation, oxidative stress, and sympathetic activity, activates brain regions that can oppose the brain "pain matrix," and finally it might influence the analgesic effects of opioids. Together, these can explain the antinociceptive effects of vagal nerve activation or of acetylcholine, the principal vagal nerve neurotransmitter. These findings form an evidence-based neurobiological rationale for testing and possibly implementing different vagal nerve-activating treatments in pain conditions. DISCUSSION: In this article, we show evidence for the relationships between vagal nerve activity and pain, and between vagal nerve activity and 5 factors that are etiologic to pain. Given the evidence and effects of the vagus nerve activation in pain, people involved in pain therapy may need to seriously consider activation of this nerve.

Objective: written emotional disclosure for 15–20?min a day over 3 to 4?days improves physical and psychological health and may benefit cancer patients. However, no studies have tested the effectiveness of guided writing in cancer patients and their partners. A randomised controlled trial tested whether writing about the patient's diagnosis and treatment of ovarian cancer using the Guided Disclosure Protocol (GDP) is effective in reducing perceived stress and improving quality of life (QoL) in ovarian cancer couples. The study also tested two theories that may account for beneficial effects of written emotional disclosure, the cognitive processing hypothesis and the social interaction hypothesis. Methods: patients and their partners (N?=?102 couples) were randomised to write at home for 15?min a day over 3?days about the patient's diagnosis and treatment using the GDP or what the patient did the previous day (control). Couples were assessed at baseline, 3- and 6-month follow-ups on the primary outcomes of perceived stress and QoL and secondary outcomes of intrusive thoughts (testing the cognitive processing hypothesis) and illness-related couple communication (testing the social interaction hypothesis). Results: there were no main effects for any outcomes. However, in patients, the GDP improved QoL if illness-related couple communication improved and buffered the effect of intrusive thoughts on perceived stress. Conclusions: the GDP might benefit patients in certain circumstances, through changes in communication (in line with the social interaction hypothesis). Further research is needed to determine whether patients benefit from interventions to improve illness-related couple communication and under which conditions

This article is made available through the Brunel Open Access Publishing Fund. Pregnancy is associated with major physiological and future psychosocial changes, and maternal adaptation to these changes is crucial for normal foetal development. Psychological stress in pregnancy predicts an earlier birth and lower birth weight. Pregnancy-specific stress contributes directly to preterm delivery. The importance of nutrition and exercise during pregnancy with regard to pregnancy outcome has long been acknowledged. This importance has only been further emphasized by the recent changes in food quality and availability, lifestyle changes and a new understanding of foetal programming's effects on adult outcomes. We hypothesised that for a successful pregnancy certain events at a nutritional, immune, psycho-emotional and genetic level should be tightly linked. Therefore, in this study we followed an ‘integrative’ approach to investigate how maternal stress, nutrition, pregnancy planning and exercise influence pregnancy outcome. A key finding of our study is that there was a significant reduction in the intake of alcohol, caffeine-containing and sugary drinks during pregnancy. However, passive smoking in the household remained unchanged. In terms of immune profile, a significant inverse correlation was noted between difficulty to ‘fight’ an infection and number of colds (r=-0.289, P=0.003) as well as the number of infections (r=-0.446, P

Recent research findings suggest neuro-modulation of tumors. Finding new modifiable prognostic factors paves the way for additional treatments, which is crucial in advanced cancer, particularly pancreatic cancer. This study examined the relationship between vagal nerve activity, indexed by heart rate variability (HRV), and overall survival (OS) in patients (N=272) with advanced pancreatic cancer. A "historical prospective" design was employed, where vagal activity and other confounders were retroactively obtained from medical charts at diagnosis, and subsequent OS was examined. HRV was obtained from 10 sec ECGs near diagnosis. Levels of C-reactive protein (CRP) were measured as an inflammatory marker. OS and survival date were obtained from medical charts and the Belgian national registry. Patients with high HRV (>20 msec) survived on average more than double the days (133.5) than those with low HRV (64.0). In a multivariate cox regression, higher initial HRV was significantly correlated with lower risk of death, independent of confounders including age and cancer treatments. This relationship was statistically mediated (accounted for) by CRP levels. Importantly, in patients who lived up to one month from diagnosis only, HRV was unrelated to CRP, while in patients surviving longer, HRV was significantly inversely related to CRP (r=-0.20, p

Psychological factors and stressful life events (LE) are considered to play a role in the onset of the metabolic syndrome (MS). We tested the association between LE and cortisol, a marker of chronic stress, with the risk of developing MS and their interaction. From a total number of 2906 men who completed a screening for the early detection of prostate cancer, 149 healthy men (mean ± SD age, 58.6 ± 7.7 years) were included in this study. Participants were assessed by the Holmes and Rahe questionnaire about their experience of LE during the previous 1-5 years. MS was diagnosed according to National Cholesterol Education Program-Adult Treatment Panel III (ATP-III) and International Diabetes Federation (IDF) criteria. Serum cortisol was measured at 08:00-09:00 h. Participants with MS (IDF criteria) reported significantly more past LE (p = 0.009) and greater summed weight of LE (p = 0.049) than those without MS. Furthermore, LE interacted with cortisol in relation to MS: in men with increased serum cortisol levels ( ≥ 13.7 μg/dl), number of LE significantly predicted MS-status (relative risk (RR) = 1.16, p = 0.03), whereas in men with low cortisol, LE were unrelated to MS (p = 0.52). We conclude that LE were significantly more prevalent in men with the MS than without the MS, according to IDF criteria, independent of the effects of age and body mass index, especially in men with increased serum cortisol levels.

Background Identifying new prognostic factors is important for guiding treatments and preventing metastasis in cancer. Vagal nerve activity may predict prognosis in cancer due to its roles in modulating inflammation, sympathetic activity and oxidative stress. This study tested the relationship between heart rate variability (HRV), a vagal nerve index, and the colon cancer (CC) marker carcinoembryonic antigen (CEA), in an ‘historical prospective’ design. Methods We examined data of 72 CC patients, without inflammatory or cardiac diseases, of whom 38 had baseline electrocardiograms (ECG) and 12 month CEA levels. We measured HRV (SDNN, RMSSD) from brief archived ECG. Multiple confounders were considered. Results Controlling for effects of tumor stage and treatment-orientation, baseline HRV predicted CEA levels at 12 months (r = −.43, p = .006). Patients with SDNN 20 ms. Conclusion These preliminary results showed that higher HRV predicts lower levels of a tumor marker, one year later, independent of confounders. This supports the hypothesized role of vagal activity in tumor modulation. Replication in larger samples is needed.

Background: Previous studies have tested the relationship between stressful life events (LE) and cancer onset, but inconsistent results have been found. One possibility is that the LE-cancer relation may depend on other biological factors pertinent to stress and cancer. Methods: This study examined the relationship between LE and prostate specific antigen (PSA) levels, a tumor marker, and whether cortisol mediates or moderates a LE-PSA relationship. During a voluntary screening for prostate cancer risk, 139 men (mean age = 57.3 years) were assessed with the Holmes and Rahe questionnaire about their LE during the past 1-5 years, and their PSA and serum cortisol levels were measured. Results: LE and cortisol alone were unrelated to PSA. However, statistically controlling for age, body mass index and the ratio of triglycerides to HDL cholesterol, we found evidence for a synergistic interaction between LE and cortisol. Among men with low cortisol, number of LE were inversely and significantly correlated with PSA (r = -0.265, p

Past studies have shown that in attempts to prevent HIV, health education yields little change in condom use. The reason may be that education fails to target barriers for changing behaviour. The present controlled pilot study tested whether psychological inoculation (PI) reduces such barriers for using male condoms. Twenty-two Nigerian women with HIV were randomly assigned to receive PI or health education (control). In the PI condition, women learned to refute sentences reflecting barriers against condom use, while controls learned how to use condoms and the consequences of their non-use. Barriers for condom use, self-efficacy to negotiate condom use with partners and actual condom use were self-reported before and one week after interventions. Results revealed that only in the PI group were there statistically significant increases in condom use negotiating self-efficacy and reductions in barriers concerning motivation, sexual satisfaction and partners. Controls reported no statistically significant changes. However, actual reported condom use was unchanged in both groups. Thus, it is feasible to conduct PI interventions in an African sample of HIV patients. Furthermore, PI can reduce cognitive barriers for condom use, while health education yields little changes in such outcomes over time. If replicated in larger samples with longer follow-ups, these findings could eventually have implications for HIV prevention in several world regions. Keywords: Psychological inoculation, condom use, HIV prevention, barriers, Africa. Des etudes anterieures ont montre que dans les tentatives pour prevenir le VIH, les efforts d’education sanitaire modifiaient peu la frequence d’utilisation d’un preservatif. C’est peut-etre parce que l’education ne parvient pas a cibler les obstacles lies au changement de comportement. La presente etude pilote controlee a tente de savoir si l’inoculation psychologique (IP) reduit ou non ces obstacles dans l’utilisation de preservatifs masculins. Vingt-deux femmes nigerianes contaminees par le VIH ont ete designees pour recevoir au hasard un PI ou une education sanitaire (temoin). Dans le cas du PI, les femmes ont appris a refuter des phrases refletant des barrieres contre l’utilisation du preservatif, alors que les temoins ont appris a utiliser des preservatifs et les consequences de leur non-utilisation. Les obstacles pour l’utilisation du preservatif, le sentiment d’efficacite personnelle a negocier l’utilisation du preservatif avec des partenaires et le reel taux d’utilisation du preservatif ont ete auto-declares avant et une semaine apres les interventions. Les resultats ont revele que c’est seulement dans le groupe d’IP qu’il y avait eu des augmentations statistiquement significatives dans le sentiment d’efficacite personnelle a negocier l’utilisation du preservatif, et dans la reductions des obstacles concernant la motivation, la satisfaction sexuelle et les partenaires. Les temoins n’ont signale aucun changement statistiquement significatif. Toutefois, le taux reel d’utilisation du preservatif est reste inchange dans les deux groupes. Ainsi, il est possible de mener des interventions d’IP dans un echantillon de patients atteints du VIH et originaires d’Afrique. En outre, l’IP peut reduire les obstacles cognitifs pour l’utilisation du preservatif, alors que les efforts de politique sanitaire n’apportent guere de changement au cours du temps dans les resultats. Si les conclusions de cette etude pilote sont les memes avec de plus grands echantillons avec davantage de suivis, elles pourraient eventuellement avoir des implications pour la prevention du VIH dans plusieurs regions du monde.

Radiation causes DNA damage, increases risk of cancer, and is associated with psychological stress responses. This article proposes an evidence-based integrative model in which psychological factors could interact with radiation by either augmenting or moderating the adverse effects of radiation on DNA integrity and eventual tumorigenesis. Based on a review of the literature, we demonstrate the following: (1) the effects of low-dose radiation exposures on DNA integrity and on tumorigenesis; (2) the effects of low-dose radiation exposure on psychological distress; (3) the relationship between psychological factors and DNA damage; and (4) the possibility that psychological stress augments and that psychological resource variables moderate radiation-induced DNA damage and risk of cancer. The additional contribution of psychological processes to radiation-DNA damage-cancer relationships needs further study, and if verified, has clinical implications.

Objective The variability in the conceptualization and categorization of social support has resulted in mixed findings regarding its role in cancer progression. This systematic review identifies and summarizes the evidence for the significance of two important indices of social support in progression of different cancers. Method We used systematic and replicable methods to search, select, and evaluate findings. Results Thirty-one longitudinal prospective findings (in 26 papers) which were selected for inclusion categorized social support into structural and functional support. The types of cancer included in these studies fell into three major categories: breast cancer (16), other cancer (10), and mixed cancers (5). Results suggest that the evidence for the relationship between social support and cancer progression is sufficiently strong for breast cancer as shown by five out of seven methodologically sound studies but consistently unconvincing for other types of cancer or in studies which combined different types of cancer. Structural support indices were found to be more frequently associated with disease progression than the indices of functional support in breast cancer. Disease-related variables such as severity, treatment, nodal status, and site of metastasis were found to be significant predictors of cancer progression, and it is suggested that these variables must be considered when conducting studies on the role of psychosocial factors in cancer-related outcomes including progression. Conclusion Methodological limitations of the studies and counterintuitive findings are discussed, and further conclusive research, particularly randomized controlled trials of social support interventions, is warranted to support the findings of this systematic review.

Recent converging evidence suggests that the brain may receive stimuli and possibly modulate tumor progression via the vagus nerve. The present study aimed to compare brain metabolism in patients with and without lung cancer and to assess if significantdifferencesexist inregionsassociatedwiththevagusnerve. Methods: Eighteen patients with lung malignancy and 19 controls underwent 18 F-FDG PET of the brain. Brain metabolism was compared using statistical parametric mapping. Results: Patients with lung malignancy showed a statistically significantly higher right cerebellar metabolism. Conclusion: This finding mayberelatedtotheroleofthecerebelluminimmuneregulation, because of its proximity to the nucleus tractus solitarius innervated by the vagus and its connections with the hypothalamus. This higher metabolism in the right cerebellum may reflect an attempt to reinstate homeostasis in functions such as respiration and immunity pertinent to lung malignancy.

The interactions between the nervous, endocrine and immune systems are studied intensively. The communication between immune and cancer cells, and multilevel and bi-directional interactions between the nervous and immune systems constitute the basis for a hypothesis assuming that the brain might monitor and modulate the processes associated with the genesis and progression of cancer. The aim of this article is to describe the data supporting this hypothesis.

BACKGROUND: Past and recent research suggests that psychological and biological factors may increase women's risk of coronary heart disease (CHD). This study examined the prevalence and correlates of self-reported heart disease among Jewish women from the Negev, a socio-economically and culturally unique region in south of Israel. METHOD: A cross-sectional design was used. We interviewed over the phone 526 randomly-selected women (mean age: 44.3+/-14.2 years) about background variables (e.g., education), biomedical risk factors (e.g., body mass index or BMI), self-reported inflammatory diseases (rheumatoid arthritis or RA, urinary infections), psychosocial factors (depression, hopelessness, self-esteem, social-support) and self-rated health and heart disease. RESULTS: Prior physician diagnosis of heart disease was reported by 8.2% of women. Age, economic difficulties, diabetes, hypertension, BMI, physical exercise, RA and urinary infections were significantly associated with reported heart disease. Of all psychosocial factors considered, hopelessness and self-esteem significantly distinguished heart disease cases from non-cases. In a multiple logistic regression, poor self-esteem, RA and hypertension were significant independent correlates of self-reported heart disease. CONCLUSIONS: Pending replication with objective measures of heart disease and a prospective design, poor self-esteem and RA may prove to be new CHD risk factors in women.

The current understanding of the pathophysiology of atherosclerosis leading to coronary artery disease (CAD) emphasizes the role of inflammatory mediators. Given the bidirectional communication between the immune and central nervous systems, an important question is whether the brain can be “informed” about and modulate CAD-related inflammation. A candidate communicator and modulator is the vagus nerve. Until now, the vagus nerve has received attention in cardiology mainly due to its role in the parasympathetic cardiovascular response. However, the vagus nerve can also “inform” the brain about peripheral inflammation since its paraganglia have receptors for interleukin-1. Furthermore, its efferent branch has a local anti-inflammatory effect. These effects have not been considered in research on the vagus nerve in CAD or in vagus nerve stimulation trials in CAD. In addition, various behavioural interventions, including relaxation, may influence CAD prognosis by affecting vagal activity. Based on this converging evidence, we propose a neuroimmunomodulation approach to atherogenesis. In this model, the vagus nerve “informs” the brain about CAD-related cytokines; in turn, activation of the vagus (via vagus nerve stimulation, vagomimetic drugs or relaxation) induces an anti-inflammatory response that can slow down the chronic process of atherogenesis.

Background: The relation between immune parameters and depression has been inconsistent, with some studies reporting immunosuppression while others reporting excessive immune responses in depressed people. This topic has not been extensively studied in the elderly, nor have researchers attempted to examine it in a non-linear manner, given previously observed contrasting findings. Objective: To examine the non-linear relation between initial white blood cell count (WBC) and depressive symptoms among acutely hospitalized elderly people. Methods: The investigation was designed as a cross-sectional analysis within a longitudinal study. Two-hundred and four patients aged 65 and above (60.3% men), admitted to internal medicine at the Soroka University Medical Center, Israel, were recruited for this study. Depression was assessed using the total 30-item Geriatric Depression Scale (GDS). WBC was obtained from medical records as well as demographic data, diagnoses and medications, and nutritional status was assessed also with self-report. To analyze a non-linear relation, we trichotomized WBC levels into low ( 10 000). Results: The prevalence of depression (GDS > 10) was 26.5%. GDS scores were significantly higher among patients with low and high WBC (P

The inflammatory microenvironment is thought to play a pivotal part in tumorigenesis. But, can the brain be informed about peripheral preclinical cancer cells? Can it modulate tumour development? One of the key routes for information to reach the brain from visceral regions is through the vagus nerve. Yet, patients with ulcers who have had a vagotomy have been shown to die from cancer more frequently than do those who have not had this procedure, and surgical and chemical vagotomy attenuates tumour-induced anorexia and leads to enhanced tumour progression. We therefore postulate that the vagus nerve participates in informing the brain about tumorigenesis by transmiting information to the brain about tumour-associated proinflammatory cytokines. Furthermore, activation of the vagus could slow tumorigenesis by suppression of peripheral proinflammatory cytokines.

Despite the fact that various studies have demonstrated the importance of the mind-body connection and fertility, the psychosocial aspects of infertility have not been adequately addressed. Fertility treatments, ranging from medical monitoring, to hormonal remedies and in vitro fertilization (IVF), are both a physical and emotional burden on women and their partners. Psychological factors such as depression, state-anxiety, and stress-induced changes in heart rate and cortisol are predictive of a decreased probability of achieving a viable pregnancy. A couple that is trying to conceive will undoubtedly experience feelings of frustration and disappointment if a pregnancy is not easily achieved. However, if the difficulties progress and the man and or woman are labelled as having fertility problems, then this may result in a severe insult to self-esteem, body image, and self-assessed masculinity or femininity. Three types of relationships have been hypothesized between psychological factors and infertility. These include: (1) psychological factors are risk factors of subsequent infertility; (2) the experience of the diagnosis and treatment of infertility causes subsequent psychological distress; (3) a reciprocal relationship exists between psychological factors and infertility. The evidence for these three relationships is reviewed and an alternative approach to the treatment of infertility including stress evaluation that precedes or is concurrent to fertility treatment is suggested.

Background: Although the outcome of patients with angiographically insignificantly narrowed coronary arteries (INCA) is not clearly defined, such lesions can progress or rupture, thus causing cardiovascular morbidity. Preventive therapy with aspirin and lipid-lowering drugs therefore seems warranted in these patients. Hypothesis: The study was undertaken to evaluate the attitude and practice of physicians toward the provision of preventive treatment to patients with INCA. Methods: The attitude of physicians was evaluated using written case histories of three patients with identical clinical features but different angiographic diagnoses. We then examined randomly chosen files of 130 patients with angiographically normal coronary arteries, 130 patients with INCA, and 130 patients with significant coronary artery disease, in relation to the use of lipid-lowering medications and achieved lipoprotein levels. Results: For the hypothetical patients, more physicians prescribed statins (78 vs. 47%, p < 0.0001) and aspirin (89 vs. 74%, p < 0.003) for patients with significant disease than they did for those with INCA. A target low-density lipoprotein (LDL) cholesterol of < 100 mg/dl was considered appropriate for significant disease by 85% of physicians compared with 40% for INCA (p < 0.0001). In the real patients, more of those with significant disease received lipid-lowering drugs and achieved the LDL target level than did those with INCA. Conclusions: Many physicians regard the need to prescribe preventive treatment as less important for patients with INCA than for patients with significant coronary disease. Additional long-term studies are warranted to elucidate the prognostic significance of INCA and the efficacy of preventive therapy in these patients.

Objective: To compare study quality and clinically meaningful effect sizes in behavioural medicine interventions and medication interventions for post-acute coronary syndrome (ACS) patients.

Recent research demonstrates the importance of inflammatory parameters in the etiology and prognosis of the acute coronary syndrome (ACS). This study explored relations between psychological factors and immunological parameters routinely measured among ACS patients. Forty-two ACS patients completed questionnaires assessing perceived-control, emotional support, hostility, and life-events 2-4 days after hospitalization. Data on total leukocytes and percentages (%) of monocytes, %neutrophils, and %lymphocytes upon admission to hospital were collected from computerized medical charts as well as various biomedical information and risk-factors (e.g., diagnosis, left-ventricle-LV functioning, smoking, and hypertension). Of all significant biomedical variables, LV-function and arrival-time correlated uniquely with total leukocytes. Controlling for LV-function and arrival-time, hostility and life-events positively correlated with %monocytes, and perceived-control and emotional-support inversely correlated with %monocytes. Emotional-support was positively correlated and life-events were negatively correlated with %neutrophils. Macrophages play a pivotal role in plaque instability, the trigger of an ACS. This initiating role, and our finding of a relationship between recruitment of monocytes and a poor psychosocial profile, predictive of ACS, are consistent with a PNI component in the pathophysiology of ACS.

Since quality of life (QOL) of hemodialysis (HD) patients is low and frequently difficult to improve by medical therapy, it is important to identify psychosocial correlates and life-domains important for HD patients' QOL. Our hypothesis was that psychosocial factors reflecting appraisal, external and internal resources/impediments correlate with QOL and compensate for adverse effects of disease-related variables on QOL. Forty-eight chronic HD-patients identified and rank-ordered life-domains important for QOL and rated their level of satisfaction with those domains. This was performed using a slightly modified version of the Self-Evaluated Individualized QOL (SEiQOL) Scale. Psychosocial factors included perceived-control (PC), social-support and hostility. Demographic and disease-related factors included age, gender, cardiovascular disease (CVD), diabetes, hematocrit, albumin and C-reactive protein. QOL was significantly correlated with PC (r = 0.65) and social-support (r = 0.38), and inversely correlated with hostility (r = -0.31), diabetes and hypoalbuminemia (all at least p < 0.05). PC mediated effects of certain variables (e.g., albumin, gender, hostility) and moderated effects of little social-support and hypoalbuminemia on QOL. Patients' most important QOL domains were health, with which satisfaction was lowest, followed by family, with which satisfaction was highest. Pending replication with larger samples, assessment and enhancement of PC may improve HD patients' QOL.

This study tested the relationship between psychosocial factors and incidence of Familial Mediterranean Fever (FMF) attacks. Forty-five children with FMF were studied retrospectively. Parents assessed their child's hostility, perceived-control, illness-behavior encouragement (IBE), family dysfunction, and reported number of attacks during the last 12 months. Hostility was positively correlated with number of attacks, especially in children below age 10 and in girls. Family dysfunction was positively correlated with attacks in girls and in children at or above age 10. IBE was inversely correlated with attacks in older children. In children below age 10, number of siblings was positively correlated with attacks, and negatively correlated with attacks in the older group. Psychosocial factors explained 27% of the variability in attacks, after controlling for age and number of siblings, with hostility remaining the only significant predictor of attacks. These findings, if replicated in a prospective study, may guide interventions for preventing FMF attacks.

Previous studies have tested the relationship between chronic stress and sex hormones, but inconsistent results have been found. One possibility is that this association may depend on other biological factors. This study examined the relationship between stressful life events (LE) and sex hormones in men, and whether cortisol is involved in this relationship. From a total number of 2906 men who completed a screening for the early detection of prostate cancer, 139 healthy men (mean +/- SD age, 57.8 +/- 5.7 years) were included in this study. Participants were assessed with the Holmes and Rahe questionnaire in relation to their experience of LE during the previous 1-5 years. Salivary and serum cortisol was measured at 08:00-09:00 h, as well as luteinizing hormone (LH), total testosterone, epinephrine (E) and norepinephrine (NE). LE weight sum and LE number positively correlated with LH (r = 0.293, p = 0.004; r = 0.220, p = 0.031, respectively). In a multiple regression analysis, LE-sum explained an additional and significant 10.4% of the variance in LH levels, after statistically controlling for the effects of age, waist circumference (WC) and BMI (F(1,90) = 6.61, p = 15.4 mu g/dl), there was a statistically significant positive relationship between LE number and total testosterone levels (p = 0.05), while LE were unrelated to total testosterone in men with low cortisol. LE correlated with sex hormones, predicting LH values, and in men with high cortisol levels shows a possible moderator effect of cortisol on the relationship between LE and total testosterone.

This article has been made available through the Brunel Open Access Publishing Fund. Pregnancy-specific stress predicts birth outcomes. We hypothesized that there is a maternal stress-GR interaction that can influence fetal birth weight. This study examined the relationship between mothers' stress and attitude towards their pregnancies, placental glucocorticoid receptors (GRs) and growth arrest-specific transcript 5 (GAS5) expression, and the status of GR polymorphism, with their infants' birth weights. GAS5 and GR α were the predominant transcripts in both term and preterm placentas, with GAS5 being primarily localized in the syncytiotrophoblasts. In an attempt to mimic moderate and high stress environment in vitro, BeWo and JEG-3 cytotrophoblast cell lines were treated with 10 nM-1000 nM cortisol. Only expression of GAS5 was significantly upregulated by cortisol in all treatments compared with basal levels, but none of the GRs changed expression significantly. In an attempt to assess a stress versus gene interaction, we studied four GR polymorphisms. In the homozygous group for Tth111I polymorphism, mothers with negative attitudes towards the pregnancy gave birth to infants with significantly lower birth weights compared to women with positive/neutral attitudes. None of the GR splice variants were associated with maternal stress. However, placental GAS5 levels were inversely correlated with maternal stress. This study points towards a potential gene-environment interaction that could be of predictive value for fetal weight. Brunel Open Access Publishing Fund

Investigations into the role of hopelessness in cancer-outcomes are gaining importance. This study examined the relations between hopelessness and psychological and serological outcomes among breast-cancer patients. Forty-nine Israeli women with breast-cancer were assessed for background data, hopelessness (helplessness and pessimism), life-changes, post-traumatic stress disorder (PTSD) symptoms and negative-affect (NA). A sub-sample (N= 21) was followed over four months for alterations in the breast-cancer serological marker CA15-3. Hopelessness was significantly correlated with PTSD-symptoms (r=.43) and NA (r= .30). Hopelessness accounted for an additional and significant 17% and 10% of the variances in PTSD-symptoms and NA. respectively, after controlling for effects of cancer-stage, age, time since diagnosis (and life-changes for PTSD). Finally, helplessness (but not pessimism) predicted changes in CA15-3, controlling for cancer-stage (r= .42. p < .05). These results support previous findings...

Recent research has begun to show the role of the activity of the vagus nerve in cancer prognosis. However, it remains unknown whether cancer severity can impair vagal nerve activity. This study combined data (N=657) of five different cancers (colorectal, pancreas, prostate, lung and ovarian) concerning patients' Heart Rate Variability (HRV), a vagal nerve activity index. These data were compared to HRV levels of a healthy sample in another study. In addition, we examined the moderating effects of age, gender and cancer stage on HRV. The mean HRV of the cancer patients sample was significantly lower (HRV=22 ms) compared to the healthy sample (HRV=50 ms) (p

Recent studies suggest that vagal nerve activity, indexed by heart rate variability (HRV), could have a prognostic role in cancer. However, most studies did not control adequately for confounders and included cardiac patients. Furthermore, the validity of this prognostic role needs to be tested in different types of cancer. The present study tested the prognostic role of HRV in prostate cancer (PC) and non-small cell lung cancer (NSCLC) patients, using a historical prospective design. HRV was derived from brief 10 sec ECGs obtained at approximately the time of diagnosis in 113 PC patients and 133 NSCLC patients. Outcomes included prostate-specific antigen (PSA) at 6 and 24 months in PC, and overall survival (OS) (for the full sample) and survival time (for the deceased patients) in NSCLC. Furthermore, the possible mediating role of C-reactive protein (CRP) was tested (in NSCLC), as well as whether age and stage moderated the relationship between HRV and prognosis in both types of cancer. In the PC patients, HRV significantly inversely predicted PSA levels at 6 and 24 months, independent of confounders. Furthermore, this was particularly significant in metastatic PC patients, indicating moderation by stage. In NSCLC patients, HRV did not predict OS and survival time, but it did positively predict survival time in patients under the age of 65, independent of confounders. Additionally, CRP was not found to mediate the relationship between HRV and OS or survival time in NSCLC. The present results partly support previous studies and extend them to two additional common types of cancer, using a more rigorous control over confounders. Together with recent experimental findings, these results propose a modulatory role of vagal nerve activity in cancer. Therefore, routine measurement of HRV in estimating prognosis in cancer may be considered.