Randomized controlled trial of multi-modular motion-assisted memory desensitization and reconsolidation (3MDR) for male military veterans with treatment-resistant post-traumatic stress disorder.

OBJECTIVE: To explore the potential efficacy of multi-modular motion-assisted memory desensitization and reprocessing (3MDR) in British military veterans with treatment-resistant service-related PTSD. METHODS: Exploratory single-blind, randomized, parallel arm, cross-over controlled trial with nested process evaluation to assess fidelity, adherence and factors that influence outcome. RESULTS: A total of 42 participants (all male) were randomized with 83% retention at 12 weeks and 86% at 26 weeks. The difference in mean Clinician-Administered PTSD Scale for DSM-5 scores between the immediate and delayed 3MDR arms was -9.38 (95% CI -17.33 to -1.44, P = 0.021) at 12 weeks and -3.59 (-14.39 to 7.20, P = 0.513) at 26 weeks when both groups had received 3MDR. The likely effect size of 3MDR was found to be 0.65. Improvements were maintained at 26-week follow-up. 3MDR was found to be acceptable to most, but not all, participants. Several factors that may impact efficacy and acceptability of 3MDR were identified. CONCLUSION: 3MDR is a promising new intervention for treatment-resistant PTSD with emerging evidence of effect.

Liquid biopsy assay for lung carcinoma using centrifuged supernatants from fine-needle aspiration specimens.

INTRODUCTION: Tumor mutation profiling is standard-of-care in lung carcinoma patients. However, comprehensive molecular profiling of small specimens, including core needle biopsy (CNB) and fine-needle aspiration (FNA) specimens, may often be inadequate due to limited tissue. Centrifuged FNA supernatants, which are typically discarded, have emerged recently as a novel liquid-based biopsy for molecular testing. In this study, we evaluate the use of lung carcinoma FNA supernatants for detecting clinically relevant mutations. METHODS: Supernatants from lung carcinoma FNA samples (n = 150) were evaluated. Samples were further analyzed using next-generation sequencing (NGS) and ultrasensitive droplet digital PCR (ddPCR). Mutation profiles in a subset of samples were compared with results derived from paired tissue samples from the same patient (n = 67) and available plasma liquid biopsy assay (n = 45). RESULTS: All 150 samples yielded adequate DNA and NGS were carried out successfully on 104 (90%) of 116 selected samples. Somatic mutations were detected in 82% of the samples and in 50% of these patients a clinically relevant mutation was identified that would qualify them for targeted therapy or a clinical trial. There was high overall concordance between the mutation profiles of supernatants and the corresponding tissue samples, with 100% concordance with concurrent FNA and 96% with concurrent CNB samples. Comparison of actionable driver mutations detected in supernatant versus plasma samples showed 84% concordance. CONCLUSIONS: FNA supernatants can provide a valuable specimen source for genotyping lung carcinoma especially in patients with insufficient tumor tissue, thereby reducing multigene mutation profiling failure rates, improving turnaround times, and avoiding repeat biopsies.

Midwives' experiences of supporting women's mental health: A mixed-method study.

OBJECTIVE: To explore midwives' skills, knowledge and experiences of supporting women's mental health. RESEARCH DESIGN AND SETTING: This paper reports the second phase of a larger project, the 'Mothers' Mood Study', which recruited women and midwives to explore their experiences of perinatal mental health and service provision and focuses on midwives' experiences of supporting women with perinatal mental health problems. This paper reports on midwives' experiences through self-administered questionnaires and focus groups. Descriptive statistics were used to analyse questionnaire data and focus group data were thematically analysed. PARTICIPANTS: All midwives employed at one Health Board in South Wales UK, were eligible to participate. Recruitment took place between February and October 2018. Questionnaires were completed by 145 midwives and 15 attended one of three focus groups. FINDINGS: Questionnaire data showed the majority of midwives had cared for women with mental health problems, most commonly anxiety (95.0%, n = 138) and depression (87.0%, n = 127). Midwives assessed women's mental health informally by observing or asking questions about mood (99.3%, n = 144), anxiety levels (94.5%, n = 137), levels of support (91.0%, n = 132) and mental health history (95.9%, n = 139). The majority of midwives (82.8%, n = 120) indicated they would make some sort of mental health assessment at least 50% of the time. Around a third of midwives 31.7% (n = 46) reported receiving training relating to perinatal mental health in the previous two years, however only 21.4% (n = 31) of these suggested this had helped them in their practice. Three themes were generated from the focus groups, 1) Conversations 2) Support 3) Knowledge and skills. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: A lack of time and continuity at appointments and a focus on physical health of mother and baby reduced the opportunity for conversations around mental health. In addition a lack of experience reduced midwives' confidence resulting in a low threshold for referring women to other services for support. Midwives' main concerns were a need for training on aspects of day-to-day practice and referral options to support women's mental health. A package of training to improved skills and confidence as well as a clear pathway of care will enable midwives to be better placed to support women's mental health.

Women's experience of mild to moderate mental health problems during pregnancy, and barriers to receiving support.

OBJECTIVE: To explore the experiences of women during pregnancy with mild to moderate mental health problems and describe the barriers to receiving support in relation to their mental health. RESEARCH DESIGN AND PARTICIPANTS: This paper reports part of a larger project which recruited women and midwives in one hospital in Wales. Participants completed questionnaires in early pregnancy in an antenatal clinic, and the characteristics of women with and without symptoms of anxiety and depression compared. All women were invited to express interest in a follow up interview in late pregnancy. Women identified to have depression and anxiety in early pregnancy, but not under the care of perinatal mental health services, were eligible for interview. Interviews were conducted with 20 women using a visual timeline to aid discussion and were thematically analysed. FINDINGS: In late pregnancy mental health disorders were reported by nine women, of which five were diagnosed during adulthood. EPDS scores found 15 women had symptoms of mild to moderate depression and GAD-7 scores indicating 15 women with mild to moderate anxiety. Three themes were identified: moods and emotions - past, present and future; expectations and control; knowledge and conversations. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Due to limited access to specialist perinatal mental health services women relied on support networks and self-care to maintain their mental health. More time and better continuity at antenatal appointments along with improved mental health literacy may increase discussions regarding women's mental health during pregnancy. In addition investment is required to develop strategies and improve access to mental health services for women with mild to moderate mental health problems.

Prevalence and predictors of poor mental health among pregnant women in Wales using a cross-sectional survey.

OBJECTIVES: To assess the prevalence of self-reported mental health problems in a cohort of women in early pregnancy. To describe the relationship between poor mental health and sociodemographic characteristics, self-efficacy and support networks. To assess if participants were representative of the local antenatal population. RESEARCH DESIGN AND SETTING: The UK government has pledged money to provide more support for women with perinatal mental health issues. Understanding the prevalence and predicting women who may need support will inform clinical practice. This paper reports part of the larger 'Mothers Mood Study', which explored women's and midwives' experience of mild to moderate perinatal mental health issues and service provision. Routinely collected population level data were analysed and a smaller cross-sectional survey design used to assess predictors of poor mental health in early pregnancy in one health board in Wales. PARTICIPANTS: Routinely collected data were extracted for all women who registered for maternity care between May 2017 and May 2018 (n = 6312) from the electronic maternity information system (pregnant population). Over a three month period 302 of these women completed a questionnaire at the antenatal clinic after an ultrasound scan (participants). Eligible women were aged ≥18 years, with sufficient spoken and written English to complete the questionnaire and a viable pregnancy of ≤18 weeks' gestation. The questionnaire collected data on sociodemographic status, self-efficacy and support networks, self-reported mental health problems. Current anxiety and depression were assessed using the General Anxiety Disorders Assessment and Edinburgh Postnatal Depression Scale. FINDINGS: Among the pregnant population 23% (n = 1490) disclosed a mental health problem during routine questioning with anxiety and depression being the most common conditions. Participants completing the detailed questionnaire were similar in age and parity to the pregnant population with similar levels of depression (15.6%; n = 15.6 v 17.3%, n = 1092). Edinburgh Postnatal Depression Scale and General Anxiety Disorder 7 scores identified 8% with symptoms of anxiety (n = 25) or depression (n = 26) and a further 24.2% (n = 73) with symptoms of mild anxiety and 25.2% (n = 76) with mild depression. Low self-efficacy (OR 1.27, 95% CI 1.12-1.45), a previous mental health problem (OR 3.95, 95% CI 1.37-11.33) and low support from family (OR 1.13, 95% CI 1.00-1.27) were found to be associated with early pregnancy anxiety and/or depression. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Around one in five women who register for maternity care may have a mental health problem. Mild to moderate anxiety and depression are common in early pregnancy. Services need to improve for women who do not currently meet the threshold for referral to perinatal mental health services. Assessment and active monitoring of mental health is recommended, in particular for pregnant women with risk factors including a history of previous mental health difficulties, poor family support or low self-efficacy.

Zinc status and age-related changes in peripheral blood leukocyte subpopulations in healthy men and women aged 55-70 y: the ZENITH study.

OBJECTIVE: To determine zinc status and age-related changes in the immune function of healthy late-middle-aged men and women (aged 55-70 y). DESIGN: Observational study. SETTING: Population of Northern Ireland. SUBJECTS: Apparently healthy, free-living individuals (45 men, 48 women) aged 55-70 y. INTERVENTION: Zinc status markers were analysed by flame atomic absorption spectrometry and commercially available kits. Immune function was assessed by flow cytometry. RESULTS: Serum and erythrocyte zinc concentrations were 13.0 (s.d. 1.40) micromol/l and 222 (s.d. 48.2) micromol/l, respectively. Serum alkaline phosphatase (ALP) concentrations were 76.8 (s.d. 16.1) U/l; women showed significantly higher concentrations of ALP (P = 0.011). Women demonstrated (1) a significant inverse correlation in naive T lymphocytes, specifically naive T-helper lymphocytes (% expression, r = -0.364, P = 0.007 and absolute count, r = -0.275, P = 0.036) with age and (2) a significant positive correlation between late activation of T lymphocytes (% expression, r = 0.299, P = 0.019 and absolute count, r = 0.260, P = 0.039) with advancing age. Men demonstrated a significant positive correlation in the % expression of (CD3-/CD16+/CD56+) natural killer (NK) cells with age (r = 0.316, P = 0.017). CONCLUSIONS: Between the ages of 55 and 70 y, healthy individuals experience significant alterations in immune function; however, such changes appear largely sex specific. Given the reported importance of adequate zinc status in maintaining optimal immune function, further studies are required to explore the effect of enhanced zinc status on emerging immune deficiencies in cell-mediated immunity in healthy 55-70 y olds.

Factors influencing the effectiveness of clinical supervision.

Clinical supervision is widely accepted as an essential prerequisite for high quality nursing care. This paper reports findings from a study that aims to identify the factors that may influence the effectiveness of clinical supervision for community mental health nurses (CMHNs) in Wales, UK. Two hundred and sixty (32%) CMHNs from an estimated total population of 817 completed the Manchester Clinical Supervision Scale (MCCS) and a demographic questionnaire. The MCCS is a 36-item questionnaire measuring the quality and effectiveness of the supervision received. Three-quarters of CMHNs reported having participated in six or more sessions of supervision in their current posts. Clinical supervision was more positively evaluated where sessions lasted for over one hour, and took place on at least a once-monthly basis. Perceived quality of supervision was also higher for those nurses who had chosen their supervisors, and where sessions took place away from the workplace. These findings have important implications for the organization and delivery of mental health nursing services.

Insulin-like growth factor-I (IGF-I) and its association with lymphocyte homeostasis in the ageing cat.

Ageing affects feline lymphocyte homeostasis in a similar pattern to that observed in other long-lived mammalian species, contributing to increased levels of morbidity and mortality in the ageing cat. Insulin-like growth factor-I (IGF-I) is now recognised as an important endocrine regulator of immunity and has been shown to decline with age in humans and rodent species. Analysis of plasma IGF-I in adult and senior cats confirmed that the older cats had significantly lower circulating levels of IGF-I. In order to determine whether an association existed between lymphocyte subpopulations and IGF-I levels in the cat, each parameter was measured and subjected to regression analysis. A highly significant association was found in vivo between plasma IGF-I and CD4(+) T-cell values in the senior group, but no such association was observed in the adult group. In order that this relationship could be examined further, in vitro studies were undertaken to investigate the effects of physiologically relevant concentrations of recombinant human IGF-I (rhIGF-l) on peripheral blood lymphocyte (PBL) cultures from adult and senior cats. While rhlGF-I induced low-level thymidine incorporation in the lymphocytes isolated from the senior group, it did not enhance the proliferative response to T-cell mitogens, Con A and PHA in either group, nor did it rescue cells from oxidatively induced apoptosis. Furthermore, the proliferative response of PBL from seniors did not attain the magnitude of that from the adults at any concentration of rhIGF-l. We propose that the observed association is not a direct effect of IGF-I on PBL, but may be mediated through an effect of IGF-I on the thymus.

DNA damage in mammalian cell lines with different antioxidant levels and DNA repair capacities.

A wide range of DNA damage is known to be caused by reactive oxygen species (ROS). Defence against the effects of such damage include damage prevention (e.g. antioxidant activity) and the removal of damaged moieties from DNA (DNA repair). Radiation (X-ray) sensitive murine lymphoma (LY) cells were seen to be more susceptible to ROS-induced damage than were radiation resistant cells. This difference was unlikely to be due to the marginally decreased DNA excision repair capacity of the sensitive cells. Radiation sensitive cells did, however, have lower endogenous antioxidant enzyme levels. Thus, the importance of assessing all levels of a cell's response to ROS, in determining the major factors leading to increased mutagen sensitivity, is emphasised.

Antiepithelial cell antibodies do not impair paediatric renal allograft survival but appear to be associated with acute viral infections.

There is a reported association between antiepithelial cell (AEC) antibodies and increased renal allograft loss in paediatric recipients. Our unit experienced a dramatic fall in 1-year graft survival so we undertook a study to determine if AEC antibodies could account for such losses. We also studied healthy children and adults as well as a group of individuals with serologically proven viral infection in an attempt to determine the prevalence and possible aetiology of these antibodies. Sera were screened for AEC antibodies in a microcytotoxicity test using a lung epithelial cell line (A549) as target. The prevalence of these antibodies in our paediatric recipients was similar to that reported elsewhere but we found no correlation between the presence of AEC antibody and allograft loss. Within the control populations, we found the antibody was more prevalent in children than in adults (p < 0.0001). We also found a strong age banding pattern, with antibody being present in 50% of children under 10 years and declining with increasing age, so that by the age of 16 years the seroprevalence was similar to that found in our adults. However, AEC antibody had a significantly higher prevalence in individuals with active viral infection than in our healthy control groups (p = 0.00003). A positive association was noted between rubella and respiratory syncytial virus and AEC antibody presence and a negative association with varicella zoster. We conclude that AEC antibodies do not correlate with increased paediatric renal allograft loss but appear to be linked to certain viral infections.

DNA damage in human T-lymphoblastoid cell line Molt-3 induced by reactive oxygen species.

In the course of studying the effect of reactive oxygen species such as superoxide anion (O2-), hydrogen peroxide (H2O2) on oxidant-sensitive human T-lymphoblastoid cell line Molt-3, O2- has been generated by the interaction of xanthine with xanthine oxidase (XOD). To confirm that H2O2 is a key intermediate for inducing DNA single-strand breaks in Molt-3 cells, studies have been carried out with pure H2O2. In the presence of xanthine + XOD or H2O2 the amount of DNA single-strand breaks has been found to increase as a function of the O2- and H2O2 concentration. Data from studies with antioxidants such as superoxide dismutase and catalase supports a mechanism of DNA damage dependent on the presence of H2O2 in Molt-3 cells. Molt-3 cells are CD4+ and sensitive to reactive oxygen stress and therefore, could be an ideal cell line for determining the relationship between oxidative stress and various diseases such as acquired immunodeficiency syndrome (AIDS).

Radioadaptation in Indian muntjac fibroblast cells induced by low intensity laser irradiation.

Earlier reports have indicated that an adaptive, protective response to ionizing radiation is inducible by pre-treatment with low intensity laser irradiation (LILI). We have investigated the potential of LILI to induce an adaptive response against the damaging effects of ionizing radiation in Indian muntjac fibroblasts. LILI at 660, but not 820 nm, at 11.5 and 23.0 J/cm2, induced an apparent adaptive response in the form of a reduction in the frequency of radiation-induced chromosome aberrations, but not in cell survival. There was also a trend towards a reduction in the level of single-stranded and double-stranded DNA breaks induced by ionizing radiation when cells were preconditioned with LILI. However, this did not contribute to the reduced chromosome aberration frequency. Further analysis revealed that the reduced aberration frequency was caused by a laser-induced extension of G2 delay. The adaptive response was therefore the result of cell cycle modulation by LILI, at a wavelength where there is no known DNA damaging effect to induce the checkpoint mechanisms that are normally responsible for altering cell cycle progression.

Vitamins C and E: acute interactive effects on biomarkers of antioxidant defence and oxidative stress.

Oxidative stress is implicated in the aetiology of many diseases; however, most supplementation trials with antioxidant micronutrients have not shown expected beneficial effects. This randomized, double-blinded, placebo-controlled study evaluated acute effects (at 90, 180min and 24h [fasting] post-ingestion) of single doses of Vitamins C (500mg) and E (400IU), alone and in combination, on biomarkers of plasma antioxidant status, lipid peroxidation and lymphocyte DNA damage in 12 healthy, consenting volunteers. Plasma ascorbic acid increased significantly (P < 0.01) within 2h of ingestion of Vitamin C, and alpha-tocopherol was significantly (P < 0.01) higher at 24h post-ingestion Vitamin E. The pattern of response was not significantly different whether Vitamin C (or Vitamin E) was taken alone or in combination, indicating no augmentation of response to one by co-ingestion of the other vitamin. No significant changes were seen in plasma FRAP in the group overall (although increases (P < 0.05) were seen at 90 and 180min post-ingestion in women after Vitamin C ingestion) or in MDA across treatments, and no evidence of increased DNA damage, or of DNA protection, was seen at any time point after Vitamin C and/or E ingestion. In conclusion, the data from this first controlled study of acute effects of single doses of Vitamin C and/or E show no evidence of either a protective or deleterious effect on DNA damage, resistance of DNA to oxidant challenge, or lipid peroxidation. No evidence of a synergistic or cooperative interaction between Vitamins C and E was seen, but further study is needed to determine possible interactive effects in a staggered supplementation cycle, and study of subjects under increased oxidative stress or with marginal antioxidant status would be useful. It would be of interest also to study the effects of these vitamins ingested with, or in, whole food, to determine if they are directly protective at doses above the minimum required to prevent deficiency, if combinations with other food components are needed for effective protection, or if Vitamins C and E are largely surrogate biomarkers of a 'healthy' diet, but are not the key protective agents.

Age-related differences in parameters of feline immune status.

In order to assess age-related differences in feline immune status, 101 domestic short haired cats were assigned to two groups, adult (2-5 years, n=50) and senior (10-14 years, n=51). Analyses of leucocyte populations, lymphocyte subsets, complement activity, serum immunoglobulins and acute-phase proteins were undertaken and revealed significant differences between the two groups. The senior group had significantly lower WBC, lymphocyte and eosinophil counts than the adult group. Neutrophil, monocyte and basophil counts did not differ between the groups. Flow cytometry analysis, in combination with differential WBC data, revealed that the absolute values (cells/l) of T-cells, B-cells and natural killer (NK) cells were significantly lower in the older animals. While serum immunoglobulins IgA and IgM were higher in the senior group when compared with the adult group, no significant differences were observed in complement activity or in serum acute-phase proteins. Our findings suggest that age-related changes to parameters of immune status in the feline model are likely to follow a similar pattern to those observed in other long-lived mammalian species.

Vitamin C decreases intracellular calcium level in human lymphoid cells.

Human lymphocytes have low levels of many antioxidant enzymes however they are know to concentrate vitamin C. Cell injury, including oxidative stress effects, is associated with calcium influx so the influence of vitamin C on the maintenance of calcium levels in leukocytes was studied. Incubation of Molt-3 human lymphoblastoid cells with physiologically relevant concentrations of vitamin C and the calcium ionophore A23187 reversed the calcium influx and increased nuclear protein level associated with the ionophore alone. It is concluded that intracellular vitamin C can inhibit calcium influx into leukocytes so helping to minimise cell damage.

Cell-cycle delay is induced in cells of a U937 promonocytic cell line by low-intensity light irradiation at 660 nm.

Visible-light irradiation (VLI) at 660 nm and 11.5 J/cm2 inhibits proliferation of cells of the U937 promonocytic cell line, as monitored by autoradiographical analysis. The S-phase cell population is reduced at 6 h post-radiation treatment. Flow cytometric analysis confirms this, and also shows that light irradiation of cells induces a statistically significant increase in G2/M cells at 6 h post-radiation treatment. It has been postulated that VLI at 660 nm can alter cell-cycle progression by affecting intracellular concentrations of ions, in particular pH and calcium. However, no significant effects of light irradiation on these intracellular ions have been observed. These effects of VLI are not a consequence of radiation-induced DNA strand breaks, therefore events other than direct DNA damage are involved. These findings demonstrate a direct photobiological effect of VLI at 660 nm on the cell cycle, and indicate a previously unsuspected mechanism for the induction of cell-cycle delay that is neither a result of changes in the concentration of intracellular ions nor initiated by DNA strand breaks.

Diet and immune function.

Adequate human nutrition is essential to maintain all normal physiological functions including defence of the self. Controversy exists about the precise constituents of diets optimal for all stages in the human life-span. Dietary composition may also need to be altered under such stressful conditions as infection or recovery from major surgery. Understanding how specific nutrients can alter immune responses may add to the quality of human lives by minimising the impact of disease morbidity and mortality. Dietary modification also offers hope of new therapeutic regimens for human diseases.

Buscopan or glucagon for endoscopic cannulation of ampulla of vater?

The number of intravenous injections of hyoscine-N-butylbromide (Buscopan) or glucagon required to maintain relaxation of the duodenum during endoscopic retrograde cholangiopancreatography (ERCP) were compared in a double blind trial of 55 patients. There was no significant difference in the number of injections. Serum amylase levels after the use of both relaxants were compared in 50 patients undergoing ERCP. No significant difference in the levels of hyperamylasaemia were found.

Specialist practice for UK community mental health nurses: the 1998--99 survey of course leaders.

Surveys of the leaders of the UK's post-qualifying education courses for community mental health nurses have taken place, on an annual basis, for over 10 years. In this paper, findings from the survey undertaken in the 1998--99 academic year are reported. These findings include: that most course leaders do not personally engage in clinical practice; that interprofessional education takes place at a minority of course centres, and that course philosophies and aims are characterised by an emphasis on both outcomes (in terms of, for example, skills acquisition, knowledge development and the ability to engage in reflective practice), and process (adult learning).

Education for community psychiatric nurses: content, structure and trends in recruitment.

Under the auspices of the Standing Advisory Group for Community Psychiatric Nursing Education, annual surveys of the leaders of the UK's post-registration courses for community psychiatric nurses (CPNs) have taken place since the 1987-88 academic year. In this paper, findings are reported from the 1997-98 survey. Thirty-two of the 39 course leaders running post-qualifying programmes for CPNs (English National Board course 812 or equivalent, and Specialist Practitioner courses) in the 1997-98 academic year responded to a nine-page postal questionnaire. Responses suggested that the majority of courses for CPNs are now offered at first degree level, with most students completing their programmes of study and clinical practice in one full-time academic year. Most courses appeared to include education in key areas of specialist content pertinent to contemporary CPN practice. Examples included: evidence-based psychosocial interventions; collaborative working with users of mental health services; inter-professional issues; cognitive-behavioural interventions; reflective practice and clinical supervision; and medication-related issues. Overall, however, courses for CPNs appeared to be characterized by considerable variations in specialist content. Possible explanations for this are offered, along with suggestions for future research.