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Behaviours, such as smoking, alcohol use, unhealthy diet, lack of physical activity and vaccination non-adherence may lead to adverse pregnancy outcomes. Pregnancy has been identified as an opportune time for midwives to support women to make health behaviour changes. To synthesise existing qualitative research exploring midwives' experiences of discussing health behaviour change with women within routine care. A systematic search was conducted across: Maternity and Infant Care, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, and Applied Social Sciences Index and Abstracts. Thematic analysis was used to synthesise the data. A professional and public advisory group provided feedback during the synthesis stage. Twenty-two studies, published between 2005 and 2023, which represented findings from eight countries, were included in the review. The meta-synthesis revealed three themes: The midwife-woman relationship; Reflective and tailored behaviour change communication; Practical barriers to behaviour change conversations. This led to one overarching theme: Although midwives recognised the importance of behaviour change discussions, these conversations were not prioritised in clinical practice. Health behaviour change discussions were de-prioritised in midwives' clinical practice. Future research should explore intervention development to support midwives with their health behaviour change communication. [ABSTRACT FROM AUTHOR]

This review aimed to develop a conceptual model of the therapeutic alliance in the context of psychotherapy and suicidal experiences from therapist and client perspectives. The protocol was pre-registered on PROSPERO (CRD42021268273). MEDLINE, PsycINFO, Web of Science, Embase and CINAHL were systematically searched from database inception to April 2024. Eligible studies were peer-reviewed, qualitative, and included client and/or therapist's perspectives of the therapeutic alliance in the context of psychotherapy and suicidal experiences. Studies were critically appraised and analysed using a meta-ethnography approach involving a reciprocal translation of studies and line of argument synthesis. Thirty-seven papers were included, generating two overarching themes; ' Working on the edge ' and ' Being ready, willing, and able to build an alliance in the context of suicidal experiences '. Therapeutic alliance in the context of suicidal experiences is unique, fluid, potentially lifesaving, and influenced by multiple inter-connected internal and external processes and systems. Clinical implications emphasise the need to improve training, supervision, and support for therapists to equip them with the additional skills required in navigating the intricacies of the therapeutic alliance with clients who have suicidal experiences. Flexibly interweaving risk assessment into therapeutic conversation was beneficial to the alliance with suicidal clients and enhanced their safety. • Alliance with suicidal clients is multifaceted and potentially lifesaving. • Readiness and ability of therapists and suicidal clients to build an alliance. • Challenges in nurturing the alliance with suicidal clients in remote therapy. • Interweaving risk assessment into therapeutic conversation benefitted the alliance. • Therapists need support in nurturing the alliance with suicidal clients. [ABSTRACT FROM AUTHOR]

• Eleven European centres reported practice patterns of image guided particle therapy (IGPT) for cranio-spinal irradiation. • There were differences in clinical IGPT practice for CSI. • The optimal workflow as defined by a group of experts was not yet translated into clinical practice. • A strong need for a consensus guideline for IGPT of CSI was identified. To investigate the current practice patterns in image-guided particle therapy (IGPT) for cranio-spinal irradiation (CSI). A multi-institutional survey was distributed to European particle therapy centres to analyse all aspects of IGPT. Based on the survey results, a Delphi consensus analysis was developed to define minimum requirements and optimal workflow for clinical practice. The centres participating in the institutional survey were invited to join the Delphi process. Eleven centres participated in the survey. Imaging for treatment planning was rather similar among the centres with Computed Tomography (CT) being the main modality. For positioning verification, 2D IGPT was more commonly used than 3D IGPT. Two centres performed routinely imaging for plan adaptation, by the rest ad hoc. Eight centres participated in the Delphi consensus analysis. The full consensus was reached on the use of CT imaging without contrast for treatment planning and the role of magnetic resonance imaging (MRI) in target and organs-at-risk delineation. There was an agreement on the necessity to perform patient position verification and correction before each isocentre. The most important outcome was the clear need for standardization and harmonization of the workflow. There were differences in CSI IGPT clinical practice among the European particle therapy centres. Moreover, the optimal workflow as identified by experts was not yet reached. There is a strong need for consensus guidelines. The state-of-the-art imaging technology and protocols need to be implemented into clinical practice to improve the quality of IGPT for CSI. [ABSTRACT FROM AUTHOR]

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignancy of the central nervous system in young children with a dismal prognosis. Prognostic markers have been extensively investigated but have not been validated. The role of radiation therapy (RT) remains controversial. We evaluated the impact of RT as part of multimodality treatment by analyzing data of a European AT/RT cohort. We retrospectively analyzed data of the European Registry for Rhabdoid Tumors and its precursors. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Potential impact of prognostic factors was analyzed using univariable and multivariable Cox regression analyses with RT as a time-dependent factor. Data of 186 children (118 male, 68 female) treated from 1990 to 2016 were evaluable. The median age at diagnosis was 1.57 years (range, 0.01-26.70 years); 47% (87/186) of the patients were under the age of 18 months. Sixty-nine percent (128/186) received RT (focal RT, n = 93; craniospinal treatment with local boost, n = 34; spinal irradiation, n = 1). The median follow-up duration of the entire cohort was 1.73 years (range, 0.06-20.11 years). The estimated PFS and OS rates were 48% (95% CI, 41%-55%) and 72% (95% CI, 65%-78%) at 1 year and 33% (95% CI, 26%-40%) and 49% (95% CI, 41%-56%) at 2 years, respectively. On multivariable analysis, RT was an independent significant prognostic factor for PFS (hazard ratio, 0.45; 95% CI, 0.27-0.75; P =.002) and OS (hazard ratio, 0.54; 95% CI, 0.32-0.93; P =.025). This analysis confirms the relevance of local therapies. RT was an independent prognostic factor for outcomes in children experiencing AT/RT. However, long-term sequelae have to be carefully evaluated and considered given the young age at time of RT. [ABSTRACT FROM AUTHOR]

• Review of the classification, clinical presentation, etiologic agents, and treatment of bacterial osteomyelitis in animals. • Provides additional species-specific information on osteomyelitis in cats and dogs, horses and a selection of other species. • Presents new treatments emerging from research and human medicine, and their potential application in veterinary medicine. Bacterial osteomyelitis in veterinary patients can be challenging to diagnose and treat, given limited therapeutic options and reported success rates. Osteomyelitis is frequently associated with surgical implant devices, including those required to optimise stability and healing of fractures. However, management of osteomyelitis sometimes necessitates the removal of these surgical implant devices in order to eradicate infection or limit implant-related osteolysis. The goal of this article is to provide a general and species-specific review of bacterial osteomyelitis in a selection of domestic veterinary species, including cats, dogs, horses, cattle and camelids, with a focus on classification, clinical presentation, aetiologic agents, and common therapeutic interventions reported in the literature. New treatment options emerging from research and human medicine will be also discussed, as they also apply to current or future care of veterinary patients with osteomyelitis. [ABSTRACT FROM AUTHOR]

Objective (1) To identify whether an online training intervention could increase midwifery students’ knowledge of behaviour change techniques (BCTs) and intentions to use them in practice. (2) To identify students’ views and current experiences of talking to women about weight-related behaviour change. Design Mixed methods study involving pre- and post-training assessments, and qualitative interviews with midwifery students. Setting Online training course delivered at a University in the North of England, UK. Participants Midwifery students in the third year of their undergraduate degree during 2015–2016. Intervention Online training focused on equipping students with knowledge of theoretically-informed BCTs, and the skills to use them opportunistically in existing practice settings. Measurements Likelihood of discussing obesity with women was assessed via a 12-item, 7-point Likert scale assessing students’ attitudes, subjective norms, perceived behavioural control, and intentions. A 14-item checklist was used to assess BCT knowledge whereby students selected recognised BCTs (of 7 correct, 7 false). Students’ views and experiences of current practice was explored through in-depth, semi-structured one-on-one interviews with a member of the research team. Findings Students’ subjective norms, perceived behavioural control, and knowledge of BCTs increased post-training but intention and attitudes did not. Interviews revealed three themes accounting for students experiences and views of behaviour change practice: (1) ‘How training fits with current encounters with maternal obesity in midwifery training’ (2) ‘TEnT PEGS prepares students for practice’, and (3) ‘Value of tailored training’. Key conclusions Online BCT training can improve the midwifery students’ confidence, knowledge and beliefs that this is part of their role. They also reported finding the training helpful in better preparing them for this challenging element of their routine practice. Implications for practice Online BCT training can be used to prepare undergraduate midwifery students for practice. [ABSTRACT FROM AUTHOR]

Background High frequency repetitive transcranial magnetic stimulation (rTMS) elicits plastic effects in excitatory and inhibitory circuits. Inter-train intervals (ITI) were initially incorporated into rTMS paradigms to avoid overheating and for safety considerations. Recent studies have shown that inclusion of ITI, as opposed to continuous stimulation, is essential for eliciting excitatory effects, but the optimal ITI remains unknown. Moreover, if ITI duration has no effect, it may be possible to substantially reduce treatment time for rTMS. Hypothesis ITI duration modulates the excitatory and disinhibitory effects of rTMS. Methods rTMS (20 Hz, 2 s trains, 1200 pulses, 100% RMT) was applied in 14 healthy individuals with ITI of 4s (duration: ∼3 min), 8s (∼5 min), 16s (∼9 min) or 32s (16.5 min) in sessions separated by ≥5 days. Effects on cortical excitability and GABA A receptor mediated short interval intracortical inhibition (SICI) were measured for 75 min following rTMS. Results The time-course of increased cortical excitability following rTMS was independent of ITI duration. There was a striking influence of ITI on SICI, whereby disinhibition increased with shorter ITI duration. Changes in cortical excitability and SICI were independent of each other. Conclusion These findings provide the first evidence to suggest that ITI may be substantially shortened without loss of rTMS effects, and warrant further investigation where rTMS is applied therapeutically. Furthermore, shorter ITIs result in greater disinhibitory effects which may be desirable in some clinical disorders and accelerated treatment paradigms. The tuning of the plasticity of cortical excitatory and inhibitory circuits to rTMS parameters in human cortex are independent. [ABSTRACT FROM AUTHOR]

Transforming growth factor β (TGFβ) is known to play an important role in early skeletal development. We previously demonstrated that loss of TGFβ receptor II (Tgfbr2) in Prx1-Cre-expressing mesenchyme results in defects in long bones, joints, and the skull vault in mice resulting from reduced naïve mesenchymal proliferation and condensation that interrupted osteoblast differentiation. In contrast, others have shown that the loss of Tgfbr2 in fully differentiated mature osteoblasts results in increased bone volume. To study the role of Tgfbr2 in immature osteoblasts, we generated Osx-Cre;Tgfbr2 fl/fl mice and found defects in the postnatal development of the skull vault and long bones as compared to controls. No discernible skeletal defects were observed in newborn mice; however, at postnatal day 24 (P24), Tgfbr2-deleted mice demonstrated short stature that correlated with reduced proliferation in the growth plate. X-ray and microCT analysis of long bone and skull from P24 mice showed reduced bone volume. Histomorphometry indicated reductions in osteoblast number but not osteoclast number. Quantitative real-time PCR demonstrated mRNA levels for the osteoblast marker, Runx2, were not altered but mRNA levels of a marker for mature osteoblasts, Bglap, were down in mutant calvaria relative to controls. The mRNA of a proliferation marker, proliferative nuclear cell antigen (PCNA), was also reduced whereas the ratio of Bax2:Bcl2 was unaltered to demonstrate no change in apoptosis. These results suggest proliferation and maturation of immature osteoblasts requires Tgfbr2 signaling and that decreased bone volume in Osx-Cre;Tgfbr2 fl/fl mice is likely due to fewer mature osteoblasts. [ABSTRACT FROM AUTHOR]

Purpose With a growing focus on the importance of men's reproductive health, including preconception health, the ways in which young men's knowledge, attitudes, and beliefs (KAB) predict their reproductive paths are understudied. To determine if reproductive KAB predicts fatherhood status, timing and residency (living with child or not). Methods Reproductive KAB and fatherhood outcomes were analyzed from the National Longitudinal Study of Adolescent Health, a 20-year, nationally representative study of individuals from adolescence into adulthood. Four measures of reproductive KAB were assessed during adolescence in waves I and II. A generalized linear latent and mixed model predicted future fatherhood status (nonfather, resident/nonresident father, adolescent father) and timing while controlling for other socio-demographic variables. Results Of the 10,253 men, 3,425 were fathers (686 nonresident/2,739 resident) by wave IV. Higher risky sexual behavior scores significantly increased the odds of becoming nonresident father (odds ratio [OR], 1.30; p < .0001), resident father (OR, 1.07; p = .007), and adolescent father (OR, 1.71; p < .0001); higher pregnancy attitudes scores significantly increased the odds of becoming a nonresident father (OR, 1.20; p < .0001) and resident father (OR, 1.11; p < .0001); higher birth control self-efficacy scores significantly decreased the odds of becoming a nonresident father (OR, .72; p < .0001) and adolescent father (OR, .56; p = .01). Conclusions Young men's KAB in adolescence predicts their future fatherhood and residency status. Strategies that address adolescent males' reproductive KAB are needed in the prevention of unintended reproductive consequences such as early and nonresident fatherhood. [ABSTRACT FROM AUTHOR]

Mechanical properties of the microenvironment regulate cell morphology and differentiation within complex organs. However, methods to restore morphogenesis and differentiation in organs in which compliance is suboptimal are poorly understood. We used mechanosensitive mouse salivary gland organ explants grown at different compliance levels together with deoxycholate extraction and immunocytochemistry of the intact, assembled matrices to examine the compliance-dependent assembly and distribution of the extracellular matrix and basement membrane in explants grown at permissive or non-permissive compliance. Extracellular matrix and basement membrane assembly were disrupted in the glands grown at low compliance compared to those grown at high compliance, correlating with defective morphogenesis and decreased myoepithelial cell differentiation. Extracellular matrix and basement membrane assembly as well as myoepithelial differentiation were restored by addition of TGFβ1 and by mechanical rescue, and mechanical rescue was prevented by inhibition of TGFβ signaling during the rescue. We detected a basal accumulation of active integrin β1 in the differentiating myoepithelial cells that formed a continuous peripheral localization around the proacini and in clefts within active sites of morphogenesis in explants that were grown at high compliance. The pattern and levels of integrin β1 activation together with myoepithelial differentiation were interrupted in explants grown at low compliance but were restored upon mechanical rescue or with application of exogenous TGFβ1. These data suggest that therapeutic application of TGFβ1 to tissues disrupted by mechanical signaling should be examined as a method to promote organ remodeling and regeneration. [ABSTRACT FROM AUTHOR]

Summary: Background: Rates of obesity are rising and previous research suggests this is not effectively dealt with in healthcare settings. Nurses are increasingly involved in lifestyle management of patients, and understanding the barriers to discussing weight with patients is likely to increase successful weight management. Obesity management is a role that nursing students will need to be equipped with and more likely to be targeted for future training developments in tackling the increasing rates of obesity. Objectives: To explore the perceptions of obesity, potential barriers to successful patient weight management and training needs of nursing students. Methods: Qualitative, semi-structured interviews were conducted with 20 nursing students. Audiotaped interviews were transcribed verbatim and analysed using an inductive thematic approach informed by principles of grounded theory. Results: Participants reported the challenge of managing obesity in healthcare practice, such as the impact of negative attitudes in healthcare practice on patient care. Although perceived as core to their training, nursing students lacked the confidence and techniques to discuss weight management with patients. Participants also perceived the nursing curriculum as lacking a focus on obesity, and reported a need for advanced communication skills training. Conclusion: Although seen as important, nurses lack the skills to facilitate weight management, leading to nurses failing to broach the issue. Practice implications: Nurse educators should consider the perceptions of current students when making curriculum developments in this area. [ABSTRACT FROM AUTHOR]

Abstract: Background: Few systematic studies have examined the reasons why patients with bipolar disorder and substance use disorders misuse alcohol and drugs of abuse. Such reasons may depend heavily on context so qualitative research methods that made no prior theoretical assumptions were employed. We explored the reasons patients give for misusing drugs and alcohol and how these relate to their illness course. Method: Qualitative semi-structured interviews and thematic analysis with a purposive sample of 15 patients with bipolar disorder and a current or past history of drug or alcohol use disorders. Results: Patients based their patterns of and reasons for substance use on previous personal experiences rather than other sources of information. Reasons for substance use were idiosyncratic, and were both mood related and unrelated. Contextual factors such as mood, drug and social often modified the patient''s personal experience of substance use. Five thematic categories emerged: experimenting in the early illness; living with serious mental illness; enjoying the effects of substances; feeling normal; and managing stress. Limitations: The prevalence of these underlying themes was not established and the results may not apply to populations with different cultural norms. Conclusions: Patterns of substance use and reasons for use are idiosyncratic to the individual and evolve through personal experience. Motivating the patient to change their substance use requires an understanding of their previous personal experience of substance use both in relation to the different phases of their bipolar disorder and their wider personal needs. [Copyright &y& Elsevier]

Craniopharyngiomas (CPs) are rare tumors of the sellar region often leading to significant comorbidities due to their close proximity to critical structures. The aim of this study was to analyze survival outcome and late toxicities after surgery and proton beam therapy (PBT) in childhood CPs. Within the prospective registry study "KiProReg" (DRKS0000536), data of 74 childhood patients with CP, receiving PBT between August 2013 to June 2022 were eligible. Late toxicities were analyzed according to the grading system of the Common Terminology Criteria for Adverse Events, version 4.0. Median follow-up since first diagnosis was 4.3 years (range, 0.8-14.7). In addition, 75.7% of patients received PBT at time of disease progression or recurrence, whereas 24.3% as part of their primary therapy (definitive or adjuvant). Predominantly (85.1%), pencil beam scanning technique was used. The median total dose and initial tumor volume were 5400 cGy relative biologic effectiveness (RBE) and 17.64 cm³ (range, 3.07-300.59), respectively. The estimated (±SE) 3-year overall survival, progression-free, and cystic failure-free survival rate after PBT were 98.2% (±1.7), 94.7% (±3.0), and 76.8% (±5.4), respectively. All local failures (n = 3) were in-field relapses necessitating intervention and occurred exclusively in patients receiving PBT at progression or recurrence. Early cystic enlargements after PBT were typically asymptomatic and self-limiting. Fatigue, headaches, vision disorders, obesity, and endocrinopathies were the predominant late toxicities. No high-grade (≥3) new-onset visual impairment or cognitive deterioration occurred compared with baseline. The presence of cognitive impairments at the end of follow-up correlated with size of the planning target volume (P =.034), D mean dose to the temporal lobes (P =.032, P =.045) and the number of surgical interventions before PBT (P =.029). Our findings demonstrate favorable local control rates using modern PBT with acceptable late toxicities. Cyst growth within 12 months after radiation therapy is typically not associated with tumor progression. Longer follow-up must be awaited to confirm results. [ABSTRACT FROM AUTHOR]

Investigates the effects of physical exercise on patients with persistent unexplained physical symptoms. Investigation on how patients use medical ideas and language to explain their symptoms and how this process influences patients' expectations and evaluations of their doctors; Analysis of symptoms and experience of doctors from 68 patients interviewed; How doctors were perceived from analysis given.

• Neural overlap is reported between autobiographical memory and prospective tasks. • It remains unclear if these findings extend to complex personal problem solving. • We report both overlap and dissociation between problem solving and memory. • We delineated the neural correlates across multiple phases of retrieval for both tasks. • These findings provide novel insight into the functions of autobiographical memory Prior research has documented engagement of a common 'core' retrieval network during autobiographical memory retrieval and higher-order prospective tasks, such as personal problem solving. This neural overlap has overwhelmingly been documented in the context of the 'elaboration phase' of retrieval, when a single mental event is simulated in detail. However, recollective and prospective tasks are often associated with generic cues, which require the retrieval and consideration of multiple conceptually-related events. This initial 'generation phase' of retrieval has received comparably little attention in the literature, leaving open questions as to how and when autobiographical memory and prospective tasks overlap within the brain. Here, we compare and contrast neural activity between autobiographical memory retrieval and personal problem solving with a focus on the initial generation phase of retrieval. In the MRI scanner, young adults completed both an autobiographical memory and a personal problem solving task. Each task consisted of a generation phase, which required participants to generate multiple past personal events or problem solutions to a given cue and a subsequent elaboration phase, where a single memory or solution was simulated in detail. A multivariate Partial Least Squares analysis revealed patterns of neural overlap between memory and problem solving during the generation phase that were distinct from the elaboration phase. Among regions commonly recruited during the generation phase was the anterior hippocampus, a structure involved in initiating mental construction and integrating concepts. Subsequent analyses demonstrated that the anterior hippocampus interacted with distinct cortical regions as a function of task, in particular the ventromedial prefrontal cortex. Together, these data provide novel evidence that neural overlap between autobiographical memory and personal problem solving does not occur solely in the context of detailed simulation but, instead, is driven by common retrieval demands. [ABSTRACT FROM AUTHOR]

Objective: To identify the communication skills medical trainees perceive themselves to avoid or use during initial clinical encounters and the areas of communication learning need they identify. Methods: 446 2nd year undergraduate medical students were invited to take part in the study. Details of four encounters with patients were entered into a web-based electronic logbook by the student. Details included perception of use, success and requests for further training from a list of communication process skills. Results: 395 (89%) students took part. Factor analysis yielded three types of skills: those used to manage the flow of interaction; the emotional content of the interaction; and structuring the interaction. Skills perceived as being used least often and least successfully and identified by the students as requiring further training were primarily those that involved managing the emotional aspects of interactions with patients rather than managing the flow of information. Conclusion: Communication training should focus further on the emotional aspects of patient interactions in order to support students during early clinical encounters. Practice implications: Skills required to manage emotional encounters need to be made more explicit to students. Opportunities to obtain feedback and develop competency should be offered as part of the core curriculum. [Copyright &y& Elsevier]

Objective: To investigate the relationship between trainee doctors' attachment style and their performance in qualifying clinical and communication skills assessments.Methods: Participants were 190 undergraduate medical students whose performance was assessed by examiners across two areas (communication and clinical skills) during their qualifying Objective Structured Clinical Examination (OSCE). Simulated patients also rated communication skills. Participants' attachment style was rated across two dimensions, avoidance and anxiety, using the Relationship Questionnaire (RQ).Results: Lower levels of attachment avoidance and anxiety significantly predicted higher performance in both communication and clinical skills.Conclusion: Trainee doctors' attachment styles are associated with patient communication and clinical performance. Further research is needed to investigate the impact of attachment on consultations between doctors and patients within clinical settings.Practice Implication: Attachment theory can inform our understanding why, for some student doctors, interacting with patients may be particularly challenging and require additional support by medical educators. [ABSTRACT FROM AUTHOR]

Rationale Prostate cancer is a leading cause of cancer in men, affecting one in eight. An ageing population coupled with increased testing indicates that the incidence of early-stage prostate cancer is rising rapidly. Treatments are effective, but all can result in chronic sexual side effects and impact on the psychological, emotional and relational components of sexual functioning. Whilst the physical consequences of treatment are well documented, we lack a comprehensive picture of the effects of localised prostate cancer treatment on men’s experience of sexual intimacy and how this may affect survivorship and recovery. Objective This study synthesises the qualitative literature related to men’s experience of sexual intimacy in the context of localised prostate cancer. Methods A systematic search strategy identified 12 studies, which were assessed using a modified version of the Critical Appraisal Skills Programme. Using Noblit and Hare’s (1988) approach, a meta-synthesis was conducted. Results Findings are organised within four inter-related themes that form the basis of a new conceptual explanatory model: (i) Loss and grief: Destroyed intimacy; (ii) Going through the motions: Artificial intimacy; (iii) Fear of failure: Avoiding intimacy and (iv) Breaking barriers: Constructing an alternative intimacy. Conclusion The LMAC (Loss, Motions, Avoidance and Construction) model provides a new way of conceptualising sexual recovery following prostate cancer treatment and opportunities for health care professionals to support men and their partners. [ABSTRACT FROM AUTHOR]

• First antimicrobial susceptibility testing (AST) of C. abortus in HeLa and macrophages. • First evidence of anti- C. abortus effects of nutlin-3 in primary human macrophages. • AST with stringent definitions of minimal inhibitory / bactericidal concentrations. Chlamydia (C.) abortus is an emerging zoonotic pathogen. Since data on its antimicrobial susceptibility are lacking, we aimed to determine minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC) for azithromycin and doxycycline in HeLa-cells and primary human macrophages (M1). We also examined the MDM2-p53-inhibitor nutlin-3, an anti-infective imidazoline analog. Azithromycin and doxycycline demonstrated MICs and MBCs equal or below their peak serum concentrations (PSC) after standard dosing in both cell types. While doxycycline exhibited an MIC 64-fold and an MBC 4-fold below its PSC in HeLa-cells, the MIC of azithromycin was 4-fold below, the MBC equal to the PSC. However, azithromycin revealed lower MBCs in M1. The pharmacological advantage of azithromycin accumulation in phagocytes and their role as chlamydial reservoirs remain uncertain. However, our data suggest possible therapeutic advantages of doxycycline in epithelial cells and we provide first evidence for an anti- C. abortus effect of nutlin-3 in M1. [ABSTRACT FROM AUTHOR]

Abstract: Vaccination is commonly used to control equine respiratory pathogens such as equine herpesvirus type 1 (EHV-1) and equine influenza virus (EIV). Here, we describe the generation and characterization of a recombinant EHV-1 modified live virus vaccine (MLV) based on a recent abortogenic EHV-1 strain, NY03. The immunogenicity and efficacy of the MLV was tested in horses in an EHV-1 vaccination/challenge experiment using the highly virulent neurovirulent EHV-1 strain OH03. Induction of a robust EHV-1-specific immune response was observed. Upon challenge infection, vaccinated horses were partially protected against disease as demonstrated by a significant reduction in clinical signs, nasal shedding and viremia levels. In addition, the NY03-based MLV was used to express the EIV H3 protein and immunogenicity was tested in horses. Expression of H3 was readily detected in NY03-H3-infected cells in vitro. Vaccination of horses resulted in the induction of a robust serological immune responses against two recent but genetically distinct EIV representatives, VA05 and NY-99, which were above the threshold predicted to be protective against development of clinical disease. [Copyright &y& Elsevier]

Abstract: Brain death is a traumatic and sudden event following a severe injury to the brain. Most patients with brain death spend the last days of life in an intensive care unit (ICU), where some families will be approached to ask for organ donation. This qualitative study was carried out with relatives of patients who had died of brain death in an ICU; all relatives were interviewed six months after the death. Twenty ICUs were recruited for this study. The next of kin of 130 patients who died during the study period were approached, and 30 (22%) agreed to be interviewed; one later withdrew. This paper focuses on the perceived palliative care needs of the 29 families. Participants valued the physical care their relatives had received, but communication and breaking bad news was a cause for concern. The facilities on many ICUs, for example, cramped relatives'' rooms and little privacy to be with the patients or to say the final goodbye, was a common theme to emerge. Bereavement follow-up did not routinely occur, and this was an identified factor noted by relatives. Families living through the period of brain death in a loved one may have particular needs in terms of end-of-life care and should be offered the support of a palliative care team through the last days of a patient''s life and into the period of bereavement. Staff training on how to communicate bad news also should be implemented as a matter of urgency. [Copyright &y& Elsevier]

Rationale Prostate cancer and its treatment have significant sexual side effects that necessitate timely patient information and open communication with healthcare professionals. However, very little is known about men's experiences of talking to clinicians about the psychosexual difficulties associated with the disease. Objective This study aims to advance understanding of men's perceptions of the communication and information challenges associated with the psychosexual aspects of prostate cancer and its treatment. Method Between October 2013 and April 2014, semi-structured interviews were conducted with 21 men from the UK who had been treated for prostate cancer. Interview transcripts were analysed using thematic analysis. Results Three themes describe the communication challenges men face: (1) It can be too soon to talk about sex; (2) the psychology of sex is missing; (3) communication is not individually tailored. Conclusions Clinicians might usefully (1) consider and discuss with patients how their psychosexual communication needs and information processing abilities may fluctuate across the cancer timeline; (2) initiate discussions about the consequences of treatment that extend beyond biological and mechanical aspects to include emotional and relational factors; (3) tailor communication to the dynamic mix of attributes that shape men's individual psychosexual needs, including their relationship status, sexual orientation, sexual motivations and values. Skills-based training in communication and psychosexual awareness may facilitate the proactive and permissive stance clinicians need to discuss sexual side effects with a heterogeneous group of patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe the development and validation of a behaviour change communication tool for medical students. METHODS: Behaviour change techniques (BCTs) were identified within the literature and used to inform a communication tool to support medical students in discussing health-related behaviour change with patients. BCTs were organized into an accessible format for medical students (the 'Tent Pegs' booklet) and validated using discriminant content validity methods with 11 expert judges. RESULTS: One-sample t-tests showed that judges reliably mapped BCTs onto six of the seven Tent Pegs domains (confidence rating means ranged from 4.0 to 5.1 out of 10, all p<=0.002). Only BCTs within the 'empowering people to change' domain were not significantly different from the value zero (mean confidence rating=1.2, p>0.05); these BCTs were most frequently allocated to the 'addressing thoughts and emotions' domain instead. CONCLUSION: BCTs within the Tent Pegs booklet are reliably allocated to corresponding behaviour change domains with the exception of those within the 'empowering people to change' domain. PRACTICE IMPLICATIONS: The existing evidence-base on BCTs can be used to directly inform development of a communication tool to support medical students facilitate health behaviour change with patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Doctors find patients with medically unexplained symptoms (MUS) challenging to manage and some hold negative attitudes towards these patients. It is unknown when and how these views form. This study examines medical trainees' beliefs and influences about MUS. METHODS: Semi-structured interviews with 43 medical trainees. Using an iterative approach, initial emergent themes were explored in subsequent interviews. Data generation continued until thematic saturation was achieved. RESULTS: Participants had received no training in MUS but had developed views about causes and management. They struggled with the concept of 'diagnosis by exclusion'. Attitudes towards patients had developed through informal clinical observation and interactions with doctors. Many welcomed formal training but identified a need to integrate theoretical learning with clinical application. CONCLUSION: Despite limited teaching, medical trainees are aware of the challenges in diagnosing and managing patients with MUS, acquiring attitudes through a hidden curriculum. To be welcomed, training must be evidence-based, theoretically informed, but clinically applicable. PRACTICAL IMPLICATIONS: Current medical training fails to equip doctors to engage with MUS and potentially fosters the development of unhelpful views of these patients. Informed teaching on diagnosis and management of MUS is necessary at a trainee level to limit the development of negative attitudes. [ABSTRACT FROM AUTHOR]

Abstract: Exposure to environmental contaminants, particularly pesticides, may be an important etiological factor in Parkinson''s disease (PD); and evidence suggests a role for microglia-dependent inflammatory and oxidative processes in nigrostriatal pathology induced by such toxins. Yet, the events mediating microglial activation and their effects are not fully known. To this end, we hypothesized that the proinflammatory cytokine, interferon-gamma (IFN-γ), may be a prime factor in the pathogenesis of PD, given its critical role in regulating microglial responses to pathogens. Indeed, the present investigation demonstrated that genetic deletion of IFN-γ protected substantia nigra pars compacta (SNc) dopamine (DA) neurons from the toxic effects of the pesticide, paraquat, and normalized changes in inflammatory and oxidative factors within this brain region. Specifically, IFN-γ knockout prevented the paraquat-induced morphological signs of microglial activation and expression of key nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, while also preventing time-dependent changes in proinflammatory enzymes (inducible nitric oxide synthase [iNOS], cyclooxygenase-2 [COX-2]), cytokines (interleukin-1β [IL-1β], tumor necrosis factor-α [TNF-α]), and signaling factors (c-Jun N-terminal kinase [JNK], p38 MAP kinase [p38], Signal transducer and activator of transcription-1 [STAT1], nuclear factor kappa B [NF-κB]). Moreover, paraquat transiently suppressed substantia nigra pars compacta expression of trophic and proneuroplastic factors (cyclic-AMP response element binding protein [CREB], brain-derived neurotrophic factor [BDNF]), and IFN-γ deficiency again reversed these effects. These data suggest that IFN-γ is important for paraquat-induced neurodegeneration and the accompanying oxidative, inflammatory, and trophic changes that characterize the response to the toxin. Targeting IFN-γ could thus have therapeutic implications for PD and other neurodegenerative conditions that involve multiple inflammatory pathways. [Copyright &y& Elsevier]

Abstract: Objective: To explore medical professionals’ and trainees’ experiences and views of behavior change talk in various health care settings to develop current understanding of the challenges that underlie this phenomenon. Methods: Qualitative, semi-structured interviews were conducted with medical professionals and trainees (n =29). Grounded theory principles informed sampling, data collection and analysis. To achieve maximum variance, participants with different levels of experience were purposively sampled from a range of primary and secondary care settings. Analysis was iterative, involving a constant comparative approach allowing emergent ideas to be tested in subsequent interviews until thematic saturation was reached. Results: Three emergent themes described reasons for not engaging in behavior change talk with patients: (1) ‘personal challenges’; (2) ‘somebody else''s responsibility’ and (3) ‘prioritizing the doctor–patient relationship’. Conclusion: Despite increasingly being recognized as a core aspect of medical practice and education, medical professionals and trainees remain unprepared to discuss health-related behavior change with patients and unclear of their roles within contemporary health care. Practice implications: Formal training in theory-based behavior change techniques is likely to help empower doctors and mitigate many of the barriers found, particularly in relation to socially and emotionally uncomfortable topics that are perceived to threaten the doctor–patient relationship. [Copyright &y& Elsevier]

Abstract: Objective: Medically unexplained symptoms (MUS) refer to bodily symptoms without a physical health explanation. In the context of MUS, reattribution is a process of attributing physical symptoms to a psychological cause. We review the use of a consultation model which employs reattribution, and which has been extensively utilised in teaching and research in primary care. Methods: Literature search for studies utilising the reattribution model. Narrative review of the results. Results: Data was extracted from 25 publications from 13 studies. The model has been modified over time and comparison between studies is limited by differences in methodology. The skills of the model can be acquired by training, which also improves practitioners'' attitudes to MUS. However impact on clinical outcomes has been mixed and this can be explained in part from the findings of nested qualitative studies. Conclusions: The reattribution model is too simplistic in its current form to address the needs of many people presenting with MUS in primary care. Reattribution of physical symptoms to psychological causes is often unnecessary. Further research is required into the effectiveness of stepped and collaborative care models in which education of primary care practitioners forms one part of a complex intervention. The consultation process is best seen as both a conversation and ongoing negotiation between doctor and patient in which there are no certainties about the presence or absence of organic pathology. [Copyright &y& Elsevier]

Abstract: Equitable access to primary care for people with common mental health problems in the UK remains problematic. The experiences of people from hard-to-reach groups offer important insights into barriers to accessing care. In this study, we report on secondary analysis of qualitative data generated within seven previously-reported studies. Thirty-three of ninety-two available transcripts were re-analysed using a new heuristic of access, generated to frame narrative-based comparative case analysis. The remaining transcripts were used to triangulate the findings via a process of collaborative analysis between a secondary researcher, naïve to research findings of the original studies, and primary researchers involved in data generation and analysis within the original studies. This method provided a rich body of ‘fine grain’ insights into the ways in which problem formulation, help-seeking, use of services and perceptions of service quality are interlinked in a recursive and socially embedded matrix of inequitable access to primary mental health care. The findings indicate both extensive commonalities between experiences of people from different ‘hard-to-reach groups’, and considerable diversity within each group. An idiographic generalisation and aggregation of this variety of experiences points to one main common facilitator (communicated availability of acceptable mental health services) and two main common barriers (lack of effective information and multiple forms of stigma) to equitable access to primary mental health care. We conclude that there is a need to provide local care that is pluralistic, adaptive, holistic, resonant and socially conscious in order to ensure that equitable access to mental health services can become a reality. [ABSTRACT FROM AUTHOR]

Abstract: Background: The evidence for the effectiveness of reattribution training are limited, and optimal service delivery is not yet established. Objectives: The objectives of this study were to establish the feasibility and to optimize the service delivery and design of a definitive randomized controlled trial (RCT) of reattribution training for patients with medically unexplained symptoms (MUSs) in routine primary care. Methodology: The study was of a cluster RCT design with the practice as the unit of randomization. Health facilitator (HF)-delivered reattribution training was compared with no reattribution training. The primary outcome measure used is doctor–patient communication in the consultation. Quantitative and qualitative methods identify barriers to effectiveness. The acceptability and feasibility of the intervention were established by attendance rates and postal survey after completion of training. Results: Sixteen practices and 70 family practitioners (FPs) were recruited with representative practice and FP characteristics. Six hours of HF reattribution training to FPs in the workplace proved feasible and acceptable with all 35 FPs completing the training. Feedback from 27 (77%) FPs who received training indicated that 25 (93%) FPs believed that specific and relevant learning achievements were made, 22 (82%) felt more confident and 21 (77%) thought the training was useful. Conclusion: HF-delivered reattribution training to whole practices is feasible and acceptable, and its effectiveness is measurable in routine primary care. [Copyright &y& Elsevier]