Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

Nontypeable Haemophilus influenzae (NTHI) is an opportunistic pathogen that is an important cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). COPD is an inflammatory disease of the airways, and exacerbations are acute inflammatory events superimposed on this background of chronic inflammation. Azithromycin (AZM) is a macrolide antibiotic with antibacterial and anti-inflammatory properties and a clinically proven potential for AECOPD prevention and management. Relationships between AZM efficacy and resistance by NTHI and between bactericidal and immunomodulatory effects on NTHI respiratory infection have not been addressed. In this study, we employed two pathogenic NTHI strains with different AZM susceptibilities (NTHI 375 [AZM susceptible] and NTHI 353 [AZM resistant]) to evaluate the prophylactic and therapeutic effects of AZM on the NTHI-host interplay. At the cellular level, AZM was bactericidal toward intracellular NTHI inside alveolar and bronchial epithelia and alveolar macrophages, and it enhanced NTHI phagocytosis by the latter cell type. These effects correlated with the strain MIC of AZM and the antibiotic dose. Additionally, the effect of AZM on NTHI infection was assessed in a mouse model of pulmonary infection. AZM showed both preventive and therapeutic efficacies by lowering NTHI 375 bacterial counts in lungs and bronchoalveolar lavage fluid (BALF) and by reducing histopathological inflammatory lesions in the upper and lower airways of mice. Conversely, AZM did not reduce bacterial loads in animals infected with NTHI 353, in which case a milder anti-inflammatory effect was also observed. Together, the results of this work link the bactericidal and anti-inflammatory effects of AZM and frame the efficacy of this antibiotic against NTHI respiratory infection.

Kyotorphin derived peptides in the relationship between analgesia and alzheimer’s disease

Tese de doutoramento, Ciências Biomédicas (Bioquímica Médica), Universidade de Lisboa, Faculdade de Medicina, 2014

D-amphetamine fails to increase extracellular dopamine levels in mice lacking alpha 1b-adrenergic receptors: relationship between functional and nonfunctional dopamine release.

It was found recently that locomotor and rewarding effects of psychostimulants and opiates were dramatically decreased or suppressed in mice lacking alpha1b-adrenergic receptors [alpha1b-adrenergic receptor knock-outs (alpha1bAR-KOs)] (Drouin et al., 2002). Here we show that blunted locomotor responses induced by 3 and 6 mg/kg d-amphetamine in alpha1bAR-KO mice [-84 and -74%, respectively, when compared with wild-type (WT) mice] are correlated with an absence of d-amphetamine-induced increase in extracellular dopamine (DA) levels in the nucleus accumbens of alpha1bAR-KO mice. Moreover, basal extracellular DA levels in the nucleus accumbens are lower in alpha1bAR-KO than in WT littermates (-28%; p < 0.001). In rats however, prazosin, an alpha1-adrenergic antagonist, decreases d-amphetamine-induced locomotor hyperactivity without affecting extracellular DA levels in the nucleus accumbens, a finding related to the presence of an important nonfunctional release of DA (Darracq et al., 1998). We show here that local d-amphetamine releases nonfunctional DA with the same affinity but a more than threefold lower amplitude in C57BL6/J mice than in Sprague Dawley rats. Altogether, this suggests that a trans-synaptic mechanism amplifies functional DA into nonfunctional DA release. Our data confirm the presence of a powerful coupling between noradrenergic and dopaminergic neurons through the stimulation of alpha1b-adrenergic receptors and indicate that nonfunctional DA release is critical in the interpretation of changes in extracellular DA levels. These results suggest that alpha1b-adrenergic receptors may be important therapeutic pharmacological targets not only in addiction but also in psychosis because most neuroleptics possess anti-alpha1-adrenergic properties.

Mitochondrial reactive oxygen species generation triggers inflammatory response and tissue injury associated with hepatic ischemia-reperfusion: Therapeutic potential of mitochondrially targeted antioxidants.

Mitochondrial reactive oxygen species generation has been implicated in the pathophysiology of ischemia-reperfusion (I/R) injury; however, its exact role and its spatial-temporal relationship with inflammation are elusive. Herein we explore the spatial-temporal relationship of oxidative/nitrative stress and inflammatory response during the course of hepatic I/R and the possible therapeutic potential of mitochondrial-targeted antioxidants, using a mouse model of segmental hepatic ischemia-reperfusion injury. Hepatic I/R was characterized by early (at 2h of reperfusion) mitochondrial injury, decreased complex I activity, increased oxidant generation in the liver or liver mitochondria, and profound hepatocellular injury/dysfunction with acute proinflammatory response (TNF-α, MIP-1α/CCL3, MIP-2/CXCL2) without inflammatory cell infiltration, followed by marked neutrophil infiltration and a more pronounced secondary wave of oxidative/nitrative stress in the liver (starting from 6h of reperfusion and peaking at 24h). Mitochondrially targeted antioxidants, MitoQ or Mito-CP, dose-dependently attenuated I/R-induced liver dysfunction, the early and delayed oxidative and nitrative stress response (HNE/carbonyl adducts, malondialdehyde, 8-OHdG, and 3-nitrotyrosine formation), and mitochondrial and histopathological injury/dysfunction, as well as delayed inflammatory cell infiltration and cell death. Mitochondrially generated oxidants play a central role in triggering the deleterious cascade of events associated with hepatic I/R, which may be targeted by novel antioxidants for therapeutic advantage.

Therapeutic riding : learning and recovery for people with disabilities

The purpose ofthis study was to explore the process oftherapeutic riding as an experiential and holistic approach to learning and recovery for people with disabilities as perceived by the providers oftherapeutic riding. To enhance the connection between theory and practice and to suggest future research, the researcher endeavoured to develop a theory that contributed to the knowledge base oftherapeutic riding, animal-assisted therapy and education, experiential education, and experiential therapy in addition to contributing to connections among them. This topic was investigated because ofthe lack ofresearch about the process of therapeutic riding, particularly from learning and a recovery perspective. Few studies have addressed how therapeutic riding outcomes are achieved or how the therapeutic riding process actually works. This study was identified as grounded theory using qualitative data through interviews and narrative reflections with therapeutic riding providers, a researcher's journal, field notes, and written documents. Grounded theory analysis was used to analyze the qualitative data. This consisted ofdoing open, axial, and selective coding. This study provided detailed descriptions ofthe research approach, researcher's involvement, participant and site selection, data collection and analysis, methodological assumptions and limitations, credibility established, and ethical considerations. The findings ofthe data analysis revealed the theme ofrelationships as central to the learning and recovery process oftherapeutic riding for people with disabilities. The significance ofthe team relationships, the horse and rider relationship, and the providers and rider relationship was found. The essential components ofthe learning and recovery process were presented in a diagram in the selective coding phase. Goals oftherapeutic riding included psycho-education; behavioural and social; physical; and equestrian. Parts ofthe process ofhow outcomes were achieved included motivation; "opens new doors;" risk; task analysis; control; communication; and environmental factors. Outcomes of therapeutic riding included independence and mobility; confidence; and transfer abilities or skills. The implications ofthese findings for theory, practice, and further research were also. explored.

Exploring the Therapeutic Alliance in Cognitive-Behavior Therapy with Children with Autism Spectrum Disorder: An Interpretative Phenomenological Approach

Abstract The therapeutic alliance (TA) is the most studied process of adult psychotherapeutic change (Zack et al., 2007) and has been found to have a moderate but robust relationship with therapeutic outcome regardless of treatment modality (Horvath, 2001). The TA is loosely described as the extent to which the therapist and the participant connect emotionally and work together towards goals. Conceptualizations of the TA with children have relied on adult models, even though it is widely acknowledged that the pediatric population will rarely willingly commit to therapy, nor readily admit to any challenges that they may be experiencing (Keeley, Geffken, McNamara & Storch, 2011). For children with Autism Spectrum Disorder (ASD) the therapeutic alliance may require an even greater retheorizing considering the communicative and social difficulties of this particular population. Despite this need, research on children with ASD and the therapeutic TA is almost non-existent. In this qualitative study, transcripts from semi-structured interviews with mothers of children with ASD were analyzed using Interpretative Phenomenological Analysis (IPA). IPA closely examines how individual people make sense of their life experiences using a theme-by-theme approach. The three interviewees were mothers whose children were participants in a nine-week Cognitive Behaviour Therapy (CBT) group for obsessive-compulsive behaviours (OCB). A total of four superordinate themes were identified: (i) Centralization and disremembering the TA, (ii) Qualities of the therapist, (iii) TA and the importance of time, and (iv) Signs of a healthy TA. The mothers’ perspectives on the TA suggest that, for them and their children, a strong TA was a required component of the therapy. Implications for clinicians and researchers are discussed.

Improving quality of mother-infant relationship and infant attachment in socioeconomically deprived community in South Africa: randomised controlled trial

Objective To assess the efficacy of an intervention designed to improve the mother-infant relationship and security of infant attachment in a South African peri-urban settlement with marked adverse socioeconomic circumstances. Design Randomised controlled trial. Setting Khayelitsha, a peri-urban settlement in South Africa. Participants 449 pregnant women. Interventions The intervention was delivered from late pregnancy and for six months postpartum. Women were visited in their homes by previously untrained lay community workers who provided support and guidance in parenting. The purpose of the intervention was to promote sensitive and responsive parenting and secure infant attachment to the mother. Women in the control group received no therapeutic input from the research team. Main outcome measures Primary outcomes: quality of mother-infant interactions at six and 12 months postpartum; infant attachment security at 18 months. Secondary outcome: maternal depression at six and 12 months. Results The intervention was associated with significant benefit to the mother-infant relationship. At both six and 12 months, compared with control mothers, mothers in the intervention group were significantly more sensitive (6 months: mean difference=0.77 (SD 0.37), t=2.10, P<0.05, d=0.24; 12 months: mean difference=0.42 (0.18), t=-2.04, P<0.05, d=0.26) and less intrusive (6 months: mean difference=0.68 (0.36), t=2.28, P<0.05, d=0.26; 12 months: mean difference=-1.76 (0.86), t=2.28, P<0.05, d=0.24) in their interactions with their infants. The intervention was also associated with a higher rate of secure infant attachments at 18 months (116/156 (74%) v 102/162 (63%); Wald=4.74, odds ratio=1.70, P<0.05). Although the prevalence of maternal depressive disorder was not significantly reduced, the intervention had a benefit in terms of maternal depressed mood at six months (z=2.05, P=0.04) on the Edinburgh postnatal depression scale). Conclusions The intervention, delivered by local lay women, had a significant positive impact on the quality of the mother-infant relationship and on security of infant attachment, factors known to predict favourable child development. If these effects persist, and if they are replicated, this intervention holds considerable promise for use in the developing world. Trial registration Current Controlled Trials ISRCTN25664149.

Improving quality of mother-infant relationship and infant attachment in socioeconomically deprived community in South Africa: randomised controlled trail

Objective To assess the efficacy of an intervention designed to improve the mother-infant relationship and security of infant attachment in a South African peri-urban settlement with marked adverse socioeconomic circumstances. Design Randomised controlled trial. Setting Khayelitsha, a peri-urban settlement in South Africa. Participants 449 pregnant women. Interventions The intervention was delivered from late pregnancy and for six months postpartum. Women were visited in their homes by previously untrained lay community workers who provided support and guidance in parenting. The purpose of the intervention was to promote sensitive and responsive parenting and secure infant attachment to the mother. Women in the control group received no therapeutic input from the research team. Main outcome measures Primary outcomes: quality of mother-infant interactions at six and 12 months postpartum; infant attachment security at 18 months. Secondary outcome: maternal depression at six and 12 months. Results The intervention was associated with significant benefit to the mother-infant relationship. At both six and 12 months, compared with control mothers, mothers in the intervention group were significantly more sensitive (6 months: mean difference=0.77 (SD 0.37), t=2.10, P<0.05, d=0.24; 12 months: mean difference=0.42 (0.18), t=−2.04 , P<0.05, d=0.26) and less intrusive (6 months: mean difference=0.68 (0.36), t=2.28, P<0.05, d=0.26; 12 months: mean difference=−1.76 (0.86), t=2.28 , P<0.05, d=0.24) in their interactions with their infants. The intervention was also associated with a higher rate of secure infant attachments at 18 months (116/156 (74%) v 102/162 (63%); Wald=4.74, odds ratio=1.70, P<0.05). Although the prevalence of maternal depressive disorder was not significantly reduced, the intervention had a benefit in terms of maternal depressed mood at six months (z=2.05, P=0.04) on the Edinburgh postnatal depression scale). Conclusions The intervention, delivered by local lay women, had a significant positive impact on the quality of the mother-infant relationship and on security of infant attachment, factors known to predict favourable child development. If these effects persist, and if they are replicated, this intervention holds considerable promise for use in the developing world.

Pathological Love: Impulsivity, Personality, and Romantic Relationship

Introduction: Pathological love (PL)-behavior characterized by providing repetitive and uncontrolled care and attention to the partner in a romantic relationship-is a rarely studied condition, despite not being rare and causing suffering. This study aims at investigating impulsivity, personality, and characteristics related to the romantic relationship in this population. Methods: Eighty-nine individuals (50 with PL; 39 individuals with no psychiatric disorder) were compared regarding impulsivity, personality, type of attachment, satisfaction with romantic relationship, and love style. Results: Individuals with PL have higher levels of impulsivity (P<.001; Barratt Impulsiveness Scale), higher self-transcendence, that is, are more unconventional and hold sense of communjon with a widerreality (P<.001; Temperament and Character Inventory) and keep dissatisfactory romantic relationships (P<.001; Adapted Relationship Assessment Scale). Conclusion: Individuals with PL present personality traits and relationship aspects that must be taken into account in devising assessment and therapeutic strategies for this population. CNS Spectr. 2009;14(5):268-274

Effects of education on the therapeutic use of oxygen by emergency nurses

Nurses' factual knowledge increased and oxygen administration decisions improved following education. Variability in nurses' knowledge and decisions, both before and after education, suggests that factual knowledge is only one component of clinical decisions. If nursing education is to improve clinical practice, then we need to better understand the relationship between factual knowledge and clinical decisions.

The therapeutic alliance : a theoretical revision for offender rehabilitation

The desired outcome of psychotherapy is positive change. A substantial body of empirical research now supports the importance of the therapeutic alliance in predicting therapeutic change. Research on therapeutic process has also been increasing. Despite these achievements, there is little theoretical understanding of how the therapeutic alliance develops and is maintained. What are the key variables in the establishment of a collaborative relationship between therapist and client that can elicit positive change in the client? Recent interest in client responsivity and effective therapy process with offenders has shed light on how little relevant theory and research exists on process issues in offender rehabilitation, compared to conventional psychotherapy. Although the general ingredients of a therapeutic alliance may be similar across therapy contexts, difficulties in creating these alliances with offenders can prompt a more complete examination of these ingredients. This article examines and critiques the dominant model of the therapeutic alliance proposed by Bordin [Bordin, E.S. (1979). The generalizability of the psychoanalytic concept of the working alliance. Psychotherapy: Theory, Research and Practice, 16, 252–260.], and then integrates it with recent research, theory, and clinical observation from the field of offender rehabilitation, to propose a Revised Theory of the Therapeutic Alliance that is particularly relevant for therapists who work to reduce future risk of criminal behavior.

Strategic facilities management system in relation with building performance; the significance and relationship

Healthcare design frequently involves complex concepts that are difficult to measure and evaluate because the building require a modern, quality, functional and therapeutic environment. For this specific reason, facilities management has become a very important support system to ensure smoothness in healthcare business. Facilities management in healthcare building is a complicated system involving multiple layers of administrative division and sub-divisions. Building performance such as building impact, function and quality prove to have significant impact on strategic facilities management. This paper will do an extensive review of strategic healthcare business management as a holistic approach and examine how facilities management can effectively manage their division with consideration and understanding of building performance. The correlation between strategic facilities management and building performance will be identified and a framework for strategic FM system with regards to building performance will be developed.

The role of the therapeutic alliance in internet-delivered cognitive-behaviour therapy

My research tested the importance of the client–practitioner relationship to therapeutic outcomes, utilising an Internet-based treatment for panic disorder. Results indicate that, while the relationship remains important when shared online, it matters less than in face-to-face settings. This calls into question conventional models of what makes psychological treatments effective.

Is the relationship between sensory-processing sensitivity and negative affect mediated by emotional regulation?

© 2015 Australian Psychological Society. Objective: Sensory-processing sensitivity refers to a trait-like difference in the extent to which individuals strongly and deeply process a variety of stimuli in the environment. While being highly sensitive has been linked to increased experiences of distress, the reasons for this are not well known. One potential mediator of this effect is emotional regulation-the set of processes influencing which emotions we have, when we have them, and how we experience and express them. This study therefore aimed to investigate whether sensory processing sensitivity is linked to negative affect via emotional regulation processes. Method: N=157 participants (n=118 females) completed online questionnaires assessing negative affect, sensory-processing sensitivity, along with two multidimensional emotional regulation measures. Results: An individual's lack of access to emotional regulation strategies, greater awareness of emotion, and lack of acceptance towards feeling distressed, acted as partial mediators between sensory-processing sensitivity and symptoms of depression. Combinations of these variables also partially mediated the relationship between sensory-processing sensitivity and symptoms of anxiety and stress. Conclusions: It is suggested that repeatedly experiencing aversive sensory-states among those with increased sensory-processing sensitivity impacts on their general awareness and acceptance of internal states and the confidence that one can regulate them. This in turn leads to the experience of negative affective states. Limitations of the present study and implications for therapeutic interventions are discussed.