Resilience in Newly Diagnosed Breast Cancer Women: The Predictive Role of Diurnal Cortisol and Social Support.

BACKGROUND: Breast cancer is currently the most prevalent malignancy among women. Psychological resilience is an important factor that diminishes the stress-related emotional and psychosocial disturbances triggered when receiving the diagnosis. Furthermore, resilience appears to be associated with cortisol, the hormonal end-product of the hypothalamic-pituitary-adrenal axis; however, further studies are needed due to the mixed results reported. Thus, we aim to examine the predictive role of social support and cortisol in resilience among breast cancer patients. METHODS: A total of 132 women with primary breast cancer completed the Medical Outcomes Study-Social Support Survey (MOS-SSS) and the Resilience Scale (RS-14) and provided four salivary samples for the estimation of participants' total daily cortisol production, for which the formula of the area under the curve with respect to the ground (AUCg) was applied. Moderation analyses were performed to study the influence of social support and AUCg on psychological resilience levels. RESULTS: The regression analyses showed a direct significant effect for the emotional support subscale of MOS-SSS on resilience and the interaction between emotional support and AUCg was also found to be statistically significant. Specifically, the conditional effect of emotional support on resilience was found to be significant at middle (M = 3.08; p < .05) and low levels (M = .59; p < .001) of AUCg. CONCLUSIONS: Our results suggest that newly diagnosed breast cancer women with middle and low diurnal cortisol profiles may benefit more from emotional support based-interventions while women with high diurnal cortisol may need more individualized therapies.

Validity and reliability of the transculturally adapted Spanish version of the Implementation Leadership Scale (ILS).

BACKGROUND: There is a need for pragmatic and reliable measures of sound factors that affect evidence-based practice (EBP) adoption and implementation in different languages and cultural environments. The Implementation Leadership Scale (ILS) is a brief and efficient measurement tool of strategic leadership for EBP implementation. The objective of this study was to assess the psychometric properties of the Spanish version of the ILS. METHODS: The process of translation of the original ILS into Spanish consisted of forward translation, panel meeting, and back-translation. Scale face and content validity compared to that of the original version were assessed and ensured before agreement on the final version. Psychometric properties were examined in 144 healthcare professionals (family physicians, pediatricians, practice and pediatric nurses) involved in implementation or improvement research projects. ILS factor structure was tested by confirmatory factor analysis (CFA). Reliability was assessed by internal consistency analysis. The Pearson correlation between the ILS and the Organizational Support dimension of the Organizational Readiness for Knowledge Translation (OR4KT) questionnaire in the subsample of pediatricians and pediatric nurses (n = 52) was estimated for convergent validity analysis. RESULTS: The CFA results indicated that the original four theorized first-order factors with a second-order Implementation Leadership factor fit the data well (χ2 = 107.70; df = 45; p < 0.001). All standardized first- and second-order factor loadings were statistically significant. Fit indexes showed acceptable figures (GFI = 0.90; CFI = 0.97; RMSEA = 0.10; SRMR = 0.053). Cronbach's alpha coefficient for the four dimensions of ILS ranged from 0.90 to 0.97, while the reliability estimated for the total scale was 0.95. Results of convergent validity revealed high correlation (r = 0.56) between the ILS and the OR4KT's Organizational Support dimension. CONCLUSION: The CFA results demonstrated that the tested first- and second-order factor structure of the 12-item Spanish version of the ILS is consistent with the factor structure of the original tool. The availability of the ILS will allow Spanish-speaking researchers to assess and advance understanding of the implementation leadership construct as a predictor of organizational implementation context.

Looking at Sex Differences in Gambling Disorder: The Predictive Role of the Early Abandonment Schema, Gambling Motives and Alexithymia in Depression.

A growing body of research indicates differences between men and women with gambling disorder. However, although alexithymia, gambling motives or abandonment have been associated with GD, women's clinical profile remains unexplored. This study aims, firstly, to explore mean differences in gambling motives (i.e. enhancement, coping and social [SOC]), the early maladaptive abandonment schema, alexithymia and depression in women and men with GD. Secondly, to analyse the correlation between the aforementioned variables as a function of sex. Thirdly, to examine the predictive role of gambling motives, early abandonment schema and alexithymia in depression as a function of sex. Lastly, to analyse the mediating role of COP between the early maladaptive abandonment schema and depression in women with GD, and the mediating role of ENH and the early maladaptive abandonment schema between alexithymia and depression in men with GD. The sample comprised 108 adults with GD diagnosis, of whom 60 were women and 48 were men. Regression and mediation analyses were carried out to explore possible sex differences in GD, through the SPSS programme. Results showed that depressive symptoms are predicted by alexithymia in men with GD and by the early maladaptive abandonment schema in women with GD. Regarding mediation analyses, the results suggest that COP mediated the relationship between early abandonment schema and depressive symptoms in females; and ENH and abandonment schema mediated the relationship between alexithymia and depressive symptoms in males. These results provide evidence of the relevance of considering sex differences when establishing therapeutic strategies in GD rehabilitation.

Comprehensive structural, infrared spectroscopic and kinetic investigations of the roles of the active-site arginine in bidirectional hydrogen activation by the [NiFe]-hydrogenase 'Hyd-2' from Escherichia coli.

The active site of [NiFe]-hydrogenases contains a strictly-conserved pendant arginine, the guanidine head group of which is suspended immediately above the Ni and Fe atoms. Replacement of this arginine (R479) in hydrogenase-2 from E. coli results in an enzyme that is isolated with a very tightly-bound diatomic ligand attached end-on to the Ni and stabilised by hydrogen bonding to the Nζ atom of the pendant lysine and one of the three additional water molecules located in the active site of the variant. The diatomic ligand is bound under oxidising conditions and is removed only after a prolonged period of reduction with H2 and reduced methyl viologen. Once freed of the diatomic ligand, the R479K variant catalyses both H2 oxidation and evolution but with greatly decreased rates compared to the native enzyme. Key kinetic characteristics are revealed by protein film electrochemistry: most importantly, a very low activation energy for H2 oxidation that is not linked to an increased H/D isotope effect. Native electrocatalytic reversibility is retained. The results show that the sluggish kinetics observed for the lysine variant arise most obviously because the advantage of a more favourable low-energy pathway is massively offset by an extremely unfavourable activation entropy. Extensive efforts to establish the identity of the diatomic ligand, the tight binding of which is an unexpected further consequence of replacing the pendant arginine, prove inconclusive.

Redox tuning of the H-cluster by second coordination sphere amino acids in the sensory [FeFe] hydrogenase from Thermotoga maritima.

[FeFe] hydrogenases are exceptionally active catalysts for the interconversion of molecular hydrogen with protons and electrons. Their active site, the H-cluster, is composed of a [4Fe-4S] cluster covalently linked to a unique [2Fe] subcluster. These enzymes have been extensively studied to understand how the protein environment tunes the properties of the Fe ions for efficient catalysis. The sensory [FeFe] hydrogenase (HydS) from Thermotoga maritima has low activity and displays a very positive redox potential for the [2Fe] subcluster compared to that of the highly active prototypical enzymes. Using site directed mutagenesis, we investigate how second coordination sphere interactions of the protein environment with the H-cluster in HydS influence the catalytic, spectroscopic and redox properties of the H-cluster. In particular, mutation of the non-conserved serine 267, situated between the [4Fe-4S] and [2Fe] subclusters, to methionine (conserved in prototypical catalytic enzymes) gave a dramatic decrease in activity. Infra-red (IR) spectroelectrochemistry revealed a 50 mV lower redox potential for the [4Fe-4S] subcluster in the S267M variant. We speculate that this serine forms a hydrogen bond to the [4Fe-4S] subcluster, increasing its redox potential. These results demonstrate the importance of the secondary coordination sphere in tuning the catalytic properties of the H-cluster in [FeFe] hydrogenases and reveal a particularly important role for amino acids interacting with the [4Fe-4S] subcluster.

Binding of exogenous cyanide reveals new active-site states in [FeFe] hydrogenases.

[FeFe] hydrogenases are highly efficient metalloenyzmes for hydrogen conversion. Their active site cofactor (the H-cluster) is composed of a canonical [4Fe-4S] cluster ([4Fe-4S]H) linked to a unique organometallic di-iron subcluster ([2Fe]H). In [2Fe]H the two Fe ions are coordinated by a bridging 2-azapropane-1,3-dithiolate (ADT) ligand, three CO and two CN- ligands, leaving an open coordination site on one Fe where substrates (H2 and H+) as well as inhibitors (e.g. O2, CO, H2S) may bind. Here, we investigate two new active site states that accumulate in [FeFe] hydrogenase variants where the cysteine (Cys) in the proton transfer pathway is mutated to alanine (Ala). Our experimental data, including atomic resolution crystal structures and supported by calculations, suggest that in these two states a third CN- ligand is bound to the apical position of [2Fe]H. These states can be generated both by "cannibalization" of CN- from damaged [2Fe]H subclusters as well as by addition of exogenous CN-. This is the first detailed spectroscopic and computational characterisation of the interaction of exogenous CN- with [FeFe] hydrogenases. Similar CN--bound states can also be generated in wild-type hydrogenases, but do not form as readily as with the Cys to Ala variants. These results highlight how the interaction between the first amino acid in the proton transfer pathway and the active site tunes ligand binding to the open coordination site and affects the electronic structure of the H-cluster.

Latent classes of eating disorders and addictions by sex: Implication of alexithymia and stressful life events in youths.

Introduction: Eating disorders (EDs) and behavioural addictions show common psychological vulnerability factors such as alexithymia and stressful life events (SLE). This study aims, firstly, to explore the prevalence and latent profiles of participants based on their risk of suffering EDs, gambling disorder (GD), alcohol and/or drug abuse, and compulsive buying (CB) by sex. Secondly, it aimed to test whether alexithymia and having experienced SLE are associated with group membership. Methods: The sample was predominantly drawn from university students and social networks. It was composed of 352 young adults between 18 and 35 years old, of whom 77.8% were women and 22.2% men. Results: The results showed that the most prevalent disorders of the sample were alcohol, EDs, CB, drugs and GD, respectively. Moreover, latent class analyses were conducted based on the risk of suffering EDs or addictions by sex. Three main profiles were found: 'Men with addictions', 'Healthy women' and 'Women with EDs'. Finally, differences in SLE and alexithymia levels were tested by latent classes. "Men with addictions" and "Women with EDs" had higher scores on alexithymia and SLE than the group of "Healthy women". However, the group of "Women with EDs" (class 3) reported significantly higher levels of SLE and alexithymia than the other two groups. Discussion and conclusion: In conclusion, we discuss the possibility that some vulnerability factors operate generally and transdiagnostically in EDs and addictive disorders. The identification of clinical phenotypes could complement and deepen prediction, prevention and treatment research in clinical settings. The need to take sex and gender differences into account is reinforced.

Professional quality of life among Spanish veterinarians.

Background: In Spain, the perceived professional quality of life among veterinarians has not been explored. Methods: Veterinarians were invited to complete an online questionnaire in which they answered the Professional Quality of Life scale, the Medical Outcomes Study Social Support Survey and the Warwick-Edinburgh Mental Well-Being Scale. Participants were asked whether they were receiving psychological therapy or were taking anxiolytics, hypnotics or antidepressant medication. Alcohol consumption was measured using the Alcohol Use Disorders Identification Test and nicotine dependence was assessed using the Fagerström test; participants were asked whether they took illegal drugs. Results: The study sample comprised a total of 602 veterinarians, most of whom reported average levels of compassion satisfaction, secondary stress trauma and burnout. Emotional support and mental wellbeing influenced participants' professional quality of life. The percentage of veterinarians in psychological therapy and/or taking anxiolytics was higher than in the general population. Conclusions: A considerable number of clinical veterinarians in Spain may be suffering from work-related stress. Our study identifies salary, emotional support and mental wellbeing as important factors that affect the professional quality of life. Interventions to improve veterinary clinicians' professional quality of life should therefore focus on these factors.

Investigating the role of the strong field ligands in [FeFe] hydrogenase: spectroscopic and functional characterization of a semi-synthetic mono-cyanide active site.

Artificial maturation of hydrogenases provides a path towards generating new semi-synthetic enzymes with novel catalytic properties. Here enzymes featuring a synthetic asymmetric mono-cyanide cofactor have been prepared using two different hydrogenase scaffolds. Their structure and reactivity was investigated in order to elucidate the design rationale behind the native di-cyanide cofactor, and by extension the second coordination sphere of the active-site pocket. Surprisingly, the choice of host enzyme was found to have a dramatic impact on reactivity. Moreover, the study shows that synthetic manipulations of the active-site can significantly increase inhibitor tolerance, as compared to native [FeFe] hydrogenase, while retaining the enzyme's native capacity for reversible catalysis.

Plasma cell-free DNA and circulating tumor cells as prognostic biomarkers in small cell lung cancer patients.

Background: Lack of biomarkers for treatment selection and monitoring in small cell lung cancer (SCLC) patients with the limited therapeutic options, result in poor outcomes. Therefore, new prognostic biomarkers are needed to improve their management. The prognostic value of cell-free DNA (cfDNA) and circulating tumor cells (CTCs) have been less explored in SCLC. Methods: We quantified cfDNA in 46 SCLC patients at different times during first-line of chemotherapy or chemo-immunotherapy. Moreover, CTCs were analyzed in 21 patients before therapy onset using CellSearch® system. The possible association between both biomarkers and patients' outcomes was investigated in order to develop a prognostic model. Results: High cfDNA levels before therapy were associated with shorter progression-free survival (PFS) and overall survival (OS). Furthermore, cfDNA levels at 3 weeks and at progression disease were also associated with patients' outcomes. Multivariate analyses confirmed the independence of cfDNA levels as a prognostic biomarker. Finally, the three-risk category prognostic model developed included Eastern Cooperative Oncology Group Performance Status (ECOG PS), gender and baseline cfDNA levels was associated with a higher risk of progression and death. Conclusions: We confirmed the prognostic utility of cfDNA quantitative analysis in SCLC patients before and during therapy. Our novel risk prognostic model in clinical practice will allow to identify patients who could benefit with actual therapies.

Effects of a Multi-Component Psychological Intervention to Cultivate Mental Health in Older Adults.

Introduction: Psychological interventions to cultivate mental health in older adults are scarce and tend to focus on and use a limited number of activities. Objective: The aim of this study was to test the effects of an intervention based on Keyes' concept of positive mental health. Methods: The intervention was conducted with 24 self-selected participants, while 34 were part of the control group. Positive mental health and distress outcomes were measured at baseline and at the end of the intervention. ANCOVA analysis and effect sizes were calculated. Results: Results showed that the intervention increased mental health (F= 18.22, p<0.001, η2= 0.334, d= 1.45, power 0.986) and decreased psychiatric symptomatology in the experimental group versus the control group (F= 7.07, p= 0.011, η2= 0.16, d= 0.87, power= 0.736), which showed no change. Discussion: Despite study limitations, the intervention effectively promoted older people's well-being. Future research, should evaluate the long-term effects of the intervention with varied older adult populations.

Bioelectrocatalytic CO2 Reduction by Redox Polymer-Wired Carbon Monoxide Dehydrogenase Gas Diffusion Electrodes.

The development of electrodes for efficient CO2 reduction while forming valuable compounds is critical. The use of enzymes as catalysts provides the advantage of high catalytic activity in combination with highly selective transformations. We describe the electrical wiring of a carbon monoxide dehydrogenase II from Carboxydothermus hydrogenoformans (ChCODH II) using a cobaltocene-based low-potential redox polymer for the selective reduction of CO2 to CO over gas diffusion electrodes. High catalytic current densities of up to -5.5 mA cm-2 are achieved, exceeding the performance of previously reported bioelectrodes for CO2 reduction based on either carbon monoxide dehydrogenases or formate dehydrogenases. The proposed bioelectrode reveals considerable stability with a half-life of more than 20 h of continuous operation. Product quantification using gas chromatography confirmed the selective transformation of CO2 into CO without any parasitic co-reactions at the applied potentials.

Comparative analysis of capture methods for genomic profiling of circulating tumor cells in colorectal cancer.

The genomic profiling of circulating tumor cells (CTCs) in the bloodstream should provide clinically relevant information on therapeutic efficacy and help predict cancer survival. Here, we contrasted the genomic profiles of CTC pools recovered from metastatic colorectal cancer (mCRC) patients using different enrichment strategies (CellSearch, Parsortix, and FACS). Mutations inferred in the CTC pools differed depending on the enrichment strategy and, in all cases, represented a subset of the mutations detected in the matched primary tumor samples. However, the CTC pools from Parsortix, and in part, CellSearch, showed diversity estimates, mutational signatures, and drug-suitability scores remarkably close to those found in matching primary tumor samples. In addition, FACS CTC pools were enriched in apparent sequencing artifacts, leading to much higher genomic diversity estimates. Our results highlight the utility of CTCs to assess the genomic heterogeneity of individual tumors and help clinicians prioritize drugs in mCRC.

A global health model integrating psychological variables involved in cancer through a longitudinal study.

Objective: The literature has shown the relevance of certain psychological variables in adjustment to cancer. However, there is a great variability, and these features could be modified through the disease process. The aim of this study is to provide an integrated and global perspective of the importance of variables such as coping, resilience, emotional control, social support, affect, and others in cancer patients through a longitudinal study, with the objective of exploring their associations and underlying interactions. Methods: The sample was composed of 71 people diagnosed with cancer who were attending psychological support at the Spanish Association Against Cancer (Biscay). We assessed the following variables in two periods of 6 months: perceived stress (PSS), emotional control (CECS), resilience (CD-RISC), coping strategies (CERQ), personality (NEOFFI), social support (MOSS), affect (PANAS), emotional distress (GHQ), quality of life (SF-12) and visual-analogic scales (EVA). Results: Results showed predictive effects of perceived stress on physical health perception (ß = -0.22; t = -3.26; p = 0.002). Mental health perception was influenced by almost all the psychological variables. Consciousness at baseline (ßCo = 0.15; p = 0.003), change in Extraversion (ßEx = 0.16; p = 0.001) and Resilience (ßRe = 0.15; p = 0.002) had significant effects on perceived mental health. Conclusion: This study provides a global health model that integrates and explores associations between psychological variables related to cancer disease. This information could be useful for guiding personalized psychotherapeutic interventions, with the aim of increasing adjustment to disease.

Eating Disorders and Intimate Partner Violence: The Influence of Fear of Loneliness and Social Withdrawal.

Eating disorders are vulnerability factors that increase the likelihood of intimate partner violence. However, the mechanisms underlying this relationship are unclear. Although eating disorders have been associated with increased perception and fear of loneliness, they have also been associated with increased social withdrawal resulting from decreased enjoyment of social situations and poorer social functioning. The purpose of the present study was to examine the mediating role of fear of loneliness in the relationship between the behavioural characteristics of eating disorders and intimate partner violence, as well as to explore the moderating role of social withdrawal in the relationship between fear of loneliness and intimate partner violence. The sample comprised 683 participants (78% female and 22% male) with a mean age of 21.14 years (SD = 2.72). The psychometric scales used were Eating Disorders Inventory (EDI 2), Emotional Dependency Questionnaire (EDQ), Coping Strategies Inventory (CSI) and the Violence Received, Exercised and Perceived in Youth and Adolescent Dating Relationships Scale (VREPS). The hypothesised model was tested by path analysis using maximum likelihood. The path analysis of the hypothesised model showed that inefficacy, fear of maturity, and impulsivity were the behavioural characteristics of eating disorders predominantly related to fear of loneliness. Fear of loneliness had no direct significant effect on any of the received violence variables. However, interaction effects indicated that there was a moderately significant effect of fear of loneliness on physical, psychological, and social violence received as a function of levels of social withdrawal. These findings show the need to take into account and work on fear of loneliness and social withdrawal among individuals with an eating disorder to decrease the likelihood of establishing violent intimate partner relationships. Improving interpersonal functioning and social support is key to recovery from eating disorders.

Methods for the Detection of Circulating Biomarkers in Cancer Patients.

Liquid biopsy has emerged as one of the main pillars for personalized oncology. The term englobes body-fluid samples which contain tumor-derived material such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and circulating extracellular vesicles (cEVs). Potential clinical application of liquid biopsy analyses includes cancer screening, detection of minimal residual disease and recurrence, therapy selection, and evaluation of acquired resistance. Despite the great developments of technology focused on circulating biomarkers characterization only cfDNA testing is nowadays implemented for the therapy selection in some advanced tumors. This can be partially explained by the fact that there is still a lack of global standardization of procedures both in the pre-analytical and analytical steps. In the present chapter, we summarize the different strategies for addressing the study of liquid biopsy taking into account their pros and cons to be applied in a clinical context and we also discuss the main technical and clinical challenges in the field of circulating biomarkers and personalized oncology.

Mediating Role of Intimate Partner Violence Between Emotional Dependence and Addictive Behaviours in Adolescents.

Objective: Intimate partner violence (IPV) has been related to emotional dependence and addictive disorders. This study aims to provide a global approach to analyse the relationship between these variables and to determine the factors underlying permanence in violent relationships. Methods: It is a non-experimental, cross-sectional correlational design study. Participants had to have at least one dating relationship for at least 1 month to complete the questionnaire, which included the following instruments: emotional dependence scale (DEN), scale of violence in dating relationships (VREP) and impulse control disorders scale (MULTICAGE CAD 4). Results: The sample consisted of 1.533 adolescents, 53.9% were male (n = 826) and 46.1% female (n = 707), between 14 and 18 years. Emotional dependence correlated significantly with received violence (r = 0.37, p < 0.001). Compulsive spending is strongly associated with emotional dependence (r = 0.21, p < 0.001), whereas sex addiction is associated with received violence to a greater extent (r = 0.18, p < 0.001). Received violence mediates on emotional dependence and addictions. Conclusion: IPV is a risk factor for the perpetuation of addictive behaviours. It is advisable to promote affective education for developing resilience and adequate coping.

Stability of the H-cluster under whole-cell conditions-formation of an Htrans-like state and its reactivity towards oxygen.

Hydrogenases are metalloenzymes that catalyze the reversible oxidation of molecular hydrogen into protons and electrons. For this purpose, [FeFe]-hydrogenases utilize a hexanuclear iron cofactor, the H-cluster. This biologically unique cofactor provides the enzyme with outstanding catalytic activities, but it is also highly oxygen sensitive. Under in vitro conditions, oxygen stable forms of the H-cluster denoted Htrans and Hinact can be generated via treatment with sulfide under oxidizing conditions. Herein, we show that an Htrans-like species forms spontaneously under intracellular conditions on a time scale of hours, concurrent with the cells ceasing H2 production. Addition of cysteine or sulfide during the maturation promotes the formation of this H-cluster state. Moreover, it is found that formation of the observed Htrans-like species is influenced by both steric factors and proton transfer, underscoring the importance of outer coordination sphere effects on H-cluster reactivity.