High-Dose versus Low-Dose Vitamin D Supplementation and Arterial Stiffness among Individuals with Prehypertension and Vitamin D Deficiency

Introduction:. Vitamin D deficiency is associated with the onset and progression of hypertension and cardiovascular disease (CVD). However, mechanisms underlying vitamin D deficiency-mediated increased risk of CVD remain unknown. We sought to examine the differential effect of high-dose versus low-dose vitamin D supplementation on markers of arterial stiffness among ~40 vitamin D deficient adults with prehypertension. Methods:. Participants were randomized to high-dose (4000 IU/d) versus low-dose (400 IU/d) oral vitamin D3 for 6 months. 24 hr ambulatory blood pressure (BP), carotid-femoral pulse wave velocity, and pulse wave analyses were obtained at baseline and after 6 months of vitamin D supplementation. Results:. There were no changes in resting BP or pulse wave velocity over 6 mo regardless of vitamin D dose (all p > 0.202). High-dose vitamin D decreased augmentation index and pressure by 12.3 ± 5.3% (p = 0.047) and 4.0 ± 1.5 mmHg (p = 0.02), respectively. However, these decreases in arterial stiffness were not associated with increases in serum 25-hydroxyvitamin D over 6 mo (p = 0.425). Conclusion:. High-dose vitamin D supplementation appears to lower surrogate measures of arterial stiffness but not indices of central pulse wave velocity. Clinical Trial Registration. This trial is registered with www.clinicaltrials.gov (Unique Identifier: NCT01240512)

Microbiome-derived carnitine mimics as previously unknown mediators of gut-brain axis communication

Alterations to the gut microbiome are associated with various neurological diseases, yet evidence of causality and identity of microbiome-derived compounds that mediate gut-brain axis interaction remain elusive. Here, we identify two previously unknown bacterial metabolites 3-methyl-4-(trimethylammonio)butanoate and 4-(trimethylammonio)pentanoate, structural analogs of carnitine that are present in both gut and brain of specific pathogen–free mice but absent in germ-free mice. We demonstrate that these compounds are produced by anaerobic commensal bacteria from the family Lachnospiraceae (Clostridiales) family, colocalize with carnitine in brain white matter, and inhibit carnitine-mediated fatty acid oxidation in a murine cell culture model of central nervous system white matter. This is the first description of direct molecular inter-kingdom exchange between gut prokaryotes and mammalian brain cells, leading to inhibition of brain cell function

Refractory depression – mechanisms and efficacy of radically open dialectical behaviour therapy (RefraMED): findings of a randomised trial on benefits and harms

Background Individuals with depression often do not respond to medication or psychotherapy. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting overcontrolled personality, common in refractory depression. Aims To compare RO DBT plus treatment as usual (TAU) for refractory depression with TAU alone (trial registration: ISRCTN 85784627). Method RO DBT comprised 29 therapy sessions and 27 skills classes over 6 months. Our completed randomised trial evaluated RO DBT for refractory depression over 18 months in three British secondary care centres. Of 250 adult participants, we randomised 162 (65%) to RO DBT. The primary outcome was the Hamilton Rating Scale for Depression (HRSD), assessed masked and analysed by treatment allocated. Results After 7 months, immediately following therapy, RO DBT had significantly reduced depressive symptoms by 5.40 points on the HRSD relative to TAU (95% CI 0.94–9.85). After 12 months (primary end-point), the difference of 2.15 points on the HRSD in favour of RO DBT was not significant (95% CI –2.28 to 6.59); nor was that of 1.69 points on the HRSD at 18 months (95% CI –2.84 to 6.22). Throughout RO DBT participants reported significantly better psychological flexibility and emotional coping than controls. However, they reported eight possible serious adverse reactions compared with none in the control group. Conclusions The RO DBT group reported significantly lower HRSD scores than the control group after 7 months, but not thereafter. The imbalance in serious adverse reactions was probably because of the controls' limited opportunities to report these

Microbiome-derived carnitine mimics as previously unknown mediators of gut-brain axis communication

Alterations to the gut microbiome are associated with various neurological diseases, yet evidence of causality and identity of microbiome-derived compounds that mediate gut-brain axis interaction remain elusive. Here, we identify two previously unknown bacterial metabolites 3-methyl-4-(trimethylammonio)butanoate and 4-(trimethylammonio)pentanoate, structural analogs of carnitine that are present in both gut and brain of specific pathogen-free mice but absent in germ-free mice. We demonstrate that these compounds are produced by anaerobic commensal bacteria from the family Lachnospiraceae (Clostridiales) family, colocalize with carnitine in brain white matter, and inhibit carnitine-mediated fatty acid oxidation in a murine cell culture model of central nervous system white matter. This is the first description of direct molecular inter-kingdom exchange between gut prokaryotes and mammalian brain cells, leading to inhibition of brain cell function.Additional co-authors: Emily K. Osterweil, Andrew S. MacDonald, Chris J. Schofield, Saverio Tardito, Josephine Bunch, Gillian Douce, Julia M. Edgar, RuAngelie Edrada-Ebel, Richard J. A. Goodwin, Richard Burchmore, Daniel M. Wal

Developing the therapeutic conversation: a conversation analysis of information giving in Family Domains Therapy

Family Domains Therapy is an intervention based on the work of Hill et al. (2014). A key feature of Family Domains Therapy is the provision of information on the model that underpins the therapy. This study is the first to use applied conversation analysis (CA) to explore the interactional impact of giving information regarding a therapeutic model during therapy sessions. Using techniques of conversation analysis this paper offers a description of the four formats therapists used to give information in this therapeutic setting (non‐technical scenarios, ‘if X then Y’ format, technical paraphrase and formulation format). Additional turn‐by‐turn conversation analysis uncovered how families were more likely to give extended responses when information was given using the format of non‐technical scenarios. Implications of the use of this type of applied conversation analysis for the study of therapeutic processes for future research and clinical practice are discussed

Post-discharge prognosis of stress cardiomyopathy in women: a retrospective cohort study

Background/objectives: There is limited information on the prognosis of stress cardiomyopathy (SCM) after hospital discharge. The aim of this retrospective cohort study was to determine the post-discharge prognosis of women with SCM compared to female controls with ST-segment elevation myocardial infarction (STEMI). Methods: SCM cases were identified through chart reviews of women hospitalized at a single tertiary care medical center between 2002 and 2012. Controls were randomly selected (2:1 ratio) among women admitted with a validated diagnosis of STEMI during the same period. The primary outcome was a composite of cardiovascular readmissions and death from any cause. Risk of the composite outcome was estimated from multivariate Cox proportional hazard regression models. Results: Over an average follow-up of 24 months, incidence rates of the composite outcome were 140/1000 person-years among cases (n = 50) and 347/1000 person-years among controls (n = 100; P < 0.001). SCM women had a lower unadjusted risk of cardiovascular readmissions and death vs. STEMI women (HR: 0.47; 95% CI: 0.27, 0.82). This difference in risk was reduced after adjustment for demographic and clinical confounders (HR: 0.64; 95% CI: 0.30, 1.33). The lower risk of developing the composite outcome among SCM women was driven by a lower risk of death, while the risk of cardiovascular readmissions was similar between groups. Conclusion: Risk of death and cardiovascular readmissions post-discharge was lower among women with SCM than among women with STEMI. Incidence rates of cardiovascular readmissions, however, were similar, indicating that SCM may not be a benign condition

Psychiatric history, post-discharge distress, and personality characteristics among incident female cases of takotsubo cardiomyopathy: A case-control study

BACKGROUND: The role of psychological factors in the onset of takotsubo cardiomyopathy (TC) is still controversial. Associations with previous psychiatric conditions are registry-based; associations with personality characteristics and psychological sequelae of TC have been largely unexplored. This case-control study sought to study pre-admission psychiatric morbidity, personality traits, and post-discharge distress in incident cases of TC. METHODS: TC cases (Mayo clinic criteria) and acute myocardial infarction (MI) controls were recruited among women admitted to two Emergency Departments in New England. Healthy controls (HC) were recruited from a volunteers\u27 registry. Preadmission psychiatric history (DSM-IV-TR) was abstracted from the medical record. PTSD symptoms (Impact of Events Scale); distress (Hospital Anxiety and Depression Scale); perceived stress (PS scale) and personality traits (optimism; hostility, type D personality) were collected via phone interview one month after discharge. RESULTS: From March 2013 through October 2015, 107 participants (45 TC, 32 MI and 30 HC) were enrolled. The prevalence of preadmission anxiety disorders was 24.4% in TC, 9.4% in MI, and 0 in HC (p = 0.007) while that of mood disorders was similar across groups. TC had higher psychological distress, perceived stress, and PTSD symptoms post-discharge vs. MI and HC. In adjusted models, PTSD symptoms remained higher in TC vs. MI (b = 0.55, p \u3c 0.05) and vs. HC (b = 0.92, p \u3c 0.01). Optimism and hostility scores were similar across groups, while type D (social inhibition) scores were higher in TC and MI vs. HC. CONCLUSIONS: Preadmission anxiety, but not depression, was associated with the occurrence of TC. High distress and PTSD symptoms post-discharge indicate that TC women may be at risk for poor psychological adjustment