Preoperative Immuno-Nutrition and Complications After Colorectal Surgery: Results of a 2-Year Prospective Study.

INTRODUCTION: Preoperative immuno-nutrition has been associated with reductions in infectious complications and length of stay, but remains unstudied in the setting of an enhanced recovery protocol. The objective was to evaluate outcomes after elective colorectal surgery with the addition of a preoperative immuno-nutrition supplement. METHODS: In October 2017, all major colorectal surgeries were given an arginine-based supplement prior to surgery. The control group consisted of cases within the same enhanced recovery protocol from three years prior. The primary outcome was a composite of overall morbidity. Secondary outcomes were infectious complications and length of stay with subgroup analysis based on degrees of malnutrition. RESULTS: Of 826 patients, 514 were given immuno-nutrition prospectively and no differences in complication rates (21.5% versus 23.9%, P = 0.416) or surgical site infections (SSIs) (6.4% versus 6.9%, P = 0.801) were observed. Hospitalization was slightly shorter in the immuno-nutrition cohort (5.0 [3.0, 7.0], versus 5.5 days [3.6, 7.9], P = 0.002). There was a clinically insignificant difference in prognostic nutrition index scores between cohorts (35.2 ± 5.6 versus 36.1 ± 5.0, P = 0.021); however, subgroup analysis (< 33, 34-38 and > 38) failed to demonstrate an association with complications (P = 0.275) or SSIs (P = 0.640) and immuno-nutrition use. CONCLUSIONS: Complication rates and SSIs were unchanged with the addition of immuno-nutrition before elective colorectal surgery. The association with length of stay is small and without clinical significance; therefore, the routine use of immuno-nutrition in this setting is of questionable benefit.

Identifying body awareness-related brain network changes after Spring Forest Qigong™ practice or P.Volve low-intensity exercise in adults with chronic low back pain: a feasibility Phase I Randomized Clinical Trial.

Background: Chronic low back pain (cLBP) affects the quality of life of 52 million Americans and leads to an enormous personal and economic burden. A multidisciplinary approach to cLBP management is recommended. Since medication has limited efficacy and there are mounting concerns about opioid addiction, the American College of Physicians and American Pain Society recommend non-pharmacological interventions, such as mind and body approaches (e.g., Qigong, yoga, Tai Chi) before prescribing medications. Of those, Qigong practice might be most accessible given its gentle movements and because it can be performed standing, sitting, or lying down. The three available Qigong studies in adults with cLBP showed that Qigong reduced pain more than waitlist and equally well than exercise. Yet, the duration and/or frequency of Qigong practice were low (<12 weeks or less than 3x/week). The objectives of this study were to investigate the feasibility of practicing Spring Forest Qigong™ or performing P.Volve low intensity exercises 3x/week for 12 weeks, feasibility of recruitment, data collection, delivery of the intervention as intended, as well as identify estimates of efficacy on brain function and behavioral outcomes after Qigong practice or exercise. To our knowledge, this is the first study investigating the feasibility of the potential effect of Qigong on brain function in adults with cLBP. Methods: We conducted a feasibility Phase I Randomized Clinical Trial. Of the 36 adults with cLBP recruited between January 2020 and June 2021, 32 were enrolled and randomized to either 12 weeks of remote Spring Forest Qigong™ practice or remote P.Volve low-intensity exercises. Participants practiced at least 3x/week for 41min/session with online videos. Our main outcome measures were the Numeric Pain Rating Scale (highest, average, and lowest cLBP pain intensity levels in the prior week), assessed weekly and fMRI data (resting-state and task-based fMRI tasks: pain imagery, kinesthetic imagery of a Qigong movement, and robot-guided shape discrimination). We compared baseline resting-state connectivity and brain activation during fMRI tasks in adults with cLBP with data from a healthy control group (n=28) acquired in a prior study. Secondary outcomes included measures of function, disability, body awareness, kinesiophobia, balance, self-efficacy, core muscle strength, and ankle proprioceptive acuity with a custom-build device. Results: Feasibility of the study design and methods was demonstrated with 30 participants completing the study (94% retention) and reporting high satisfaction with the programs; 96% adherence to P.Volve low-intensity exercises, and 128% of the required practice intensity for Spring Forest Qigong™ practice. Both groups saw promising reductions in low back pain (effect sizes Cohen's d =1.01-2.22) and in most other outcomes ( d =0.90-2.33). Markers of ankle proprioception were not significantly elevated in the cLBP group after the interventions. Brain imaging analysis showed weaker parietal operculum and insula network connectivity in adults with cLBP (n=26), compared to data from a healthy control group (n=28). The pain imagery task elicited lower brain activation of insula, parietal operculum, angular gyrus and supramarginal gyrus at baseline in adults with cLBP than in healthy adults. Adults with cLBP had lower precentral gyrus activation than healthy adults for the Qigong movement and robot task at baseline. Pre-post brain function changes showed individual variability: Six (out of 13) participants in the Qigong group showed increased activation in the parietal operculum, angular gyrus, supramarginal gyrus, and precentral gyrus during the Qigong fMRI task. Interpretation: Our data indicate the feasibility and acceptability of using Spring Forest Qigong™ practice or P.Volve low-intensity exercises for cLBP relief showing promising results in terms of pain relief and associated symptoms. Our brain imaging results indicated brain function improvements after 12 weeks of Qigong practice in some participants, pointing to the need for further investigation in larger studies. Trial registration number: ClinicalTrials.gov: NCT04164225 .

Biomarker Response to Mindfulness Intervention in Veterans Diagnosed with Post-traumatic Stress Disorder.

Objectives: This study evaluates the effects of treatment with mindfulness-based stress reduction (MBSR) compared to the active control, present-centered group therapy (PCGT), on morning plasma cortisol, interleukin-6 (IL-6), and C-reactive protein (CRP) in veterans diagnosed with post-traumatic stress disorder (PTSD). Methods: In a post hoc exploratory analysis, we pooled biomarkers and clinical outcomes of mindfulness, PTSD, and depression from two randomized controlled trials comparing MBSR (n = 104) to PCGT (n = 106) in U.S. military veterans diagnosed with PTSD. Linear mixed-effects modeling was used to evaluate associations between changes in biomarkers and clinical outcomes from baseline to 9-week primary endpoint and 16-week follow-up endpoint. Results: Cortisol levels were inversely related to self-reported PTSD symptoms at baseline (p = 0.02). Cortisol increased from baseline to 9-week endpoint for both groups, but significantly less so in the MBSR group compared to PCGT group (mean difference 1.69 ± 0.8 SE; p = 0.035). Changes in IL-6 and CRP did not differ between groups at either baseline or week 9. From baseline to week 9, increased mindfulness was significantly associated with increased cortisol (p = 0.02) and decreased PTSD and depression severity (p < 0.01). Increased IL-6 and CRP were significantly associated with decreased PTSD severity (p < 0.05), but not depression. Pooled analysis corroborated earlier findings that MBSR is significantly better than PCGT in improving clinical outcomes. Increased mindfulness was strongly associated with improved symptoms. Conclusions: Increased mindfulness is associated with a recalibration of cortisol levels which may be indicative of therapeutic response, especially in patients with lower baseline cortisol. Furthermore, mindfulness-based practices improve symptoms of PTSD and depression in a significant correlation with self-reported levels of mindfulness. Clinical Trial Registration clinicaltrialsgov: NCT01532999 and NCT01548742.

Interoception Underlies Therapeutic Effects of Mindfulness Meditation for Posttraumatic Stress Disorder: A Randomized Clinical Trial.

BACKGROUND: Mindfulness-based interventions have proven efficacy in treating posttraumatic stress disorder (PTSD), but the neurobiological mechanism underlying the therapeutic effects is unknown. As mindfulness meditation cultivates attention to the present moment and bodily sensations, neural functions related to interoception (i.e., central processes of bodily signals) might be such a mechanism. METHODS: We conducted a clinical trial in which veterans with PTSD were randomly assigned to receive an 8-week mindfulness-based stress reduction (MBSR) intervention (n = 47) or an active control intervention (present-centered group therapy; n = 51). We assessed pre- and postintervention PTSD symptoms and electroencephalography measures of neural outcomes, including spontaneous brain activity, cognitive task-related brain responses, and interoceptive brain responses (heartbeat-evoked brain responses). We conducted statistical causal mediation analyses using treatment type as a predictor, pre- and postintervention measures of symptom severity as treatment response, and the neural outcomes as mediators. RESULTS: Compared with the control group, the MBSR group had greater improvements in PTSD symptoms and increases in spontaneous alpha power (8-13 Hz), task-related frontal theta power (4-7 Hz in 140-220 ms after stimulus), and frontal theta heartbeat-evoked brain responses (3-5 Hz and 265-336 ms after R peak). The mediation analysis using latent difference score modeling revealed that only changes in frontal theta heartbeat-evoked brain responses mediated the MBSR treatment effect. CONCLUSIONS: Mindfulness meditation improves brain functions of attentional control and resting brain states reflective of internally oriented relaxation. However, interoceptive neural functions enhanced by MBSR seem to be a primary cerebral mechanism that improves symptoms of PTSD.

Corrigendum: Methylation of FKBP5 and SLC6A4 in Relation to Treatment Response to Mindfulness Based Stress Reduction for Posttraumatic Stress Disorder.

[This corrects the article DOI: 10.3389/fpsyt.2018.00418.].

Management of Fracture Risk in Patients with Chronic Obstructive Pulmonary Disease (COPD): Building a UK Consensus Through Healthcare Professional and Patient Engagement.

Introduction: Osteoporosis and bone fractures are common in chronic obstructive pulmonary disease (COPD) and contribute significantly to morbidity and mortality. Current national guidance on COPD management recommends addressing bone health in patients, however, does not detail how. This consensus outlines key elements of a structured approach to managing bone health and fracture risk in patients with COPD. Methods: A systematic approach incorporating multifaceted methodologies included detailed patient and healthcare professional (HCP) surveys followed by a roundtable meeting to reach a consensus on what a pathway would look like. Results: The surveys revealed that fracture risk was not always assessed despite being recognised as an important aspect of COPD management by HCPs. The majority of the patients also stated they would be receptive to discussing treatment options if found to be at risk of osteoporotic fractures. Limited time and resource allocation were identified as barriers to addressing bone health during consultations. The consensus from the roundtable meeting was that a proactive systematic approach to assessing bone health should be adopted. This should involve using fracture risk assessment tools to identify individuals at risk, investigating secondary causes of osteoporosis if a diagnosis is made and reinforcing non-pharmacological and preventative measures such as smoking cessation, keeping active and pharmacological management of osteoporosis and medicines management of corticosteroid use. Practically, prioritising patients with important additional risk factors, such as previous fragility fractures, older age and long-term oral corticosteroid use for an assessment, was felt required. Conclusion: There is a need for integrating fracture risk assessment into the COPD pathway. Developing a systematic and holistic approach to addressing bone health is key to achieving this. In tandem, opportunities to disseminate the information and educational resources are also required.

Neural correlates of clinical improvement in response to N-acetylcysteine in adolescents with non-suicidal self-injury.

Non-suicidal self-injury (NSSI) is a serious clinical problem that is common in adolescents. Novel, biologically-informed approaches for treating NSSI in adolescents are needed to prevent negative outcomes such as chronic NSSI and future suicide attempts. N-acetylcysteine (NAC) has been used successfully to address other conditions that involve repetitive maladaptive behaviors and may have utility in addressing NSSI. This study explored neural circuit changes following an open-label, 8-week trial of NAC in female adolescents with NSSI. We measured whole-brain resting-state functional connectivity (RSFC) of the amygdala and the nucleus accumbens before and after treatment using resting-state functional neuroimaging. Usable neuroimaging data from both pre- and post-treatment were available for 18 participants. Reduction in NSSI frequency was associated with a decrease in left amygdala RSFC with right supplementary motor area (SMA), but with an increase in right amygdala RSFC with right inferior frontal cortex. For nucleus accumbens, a reduction in NSSI frequency was associated with a decrease in connectivity between right nucleus accumbens and left superior medial frontal cortex. We also report change in similar circuits accompanying clinical improvement in depression and global psychopathology measures. These preliminary findings suggest amygdala and nucleus accumbens-based circuits as potential treatment targets, and set the stage for future research designed to confirm these neural targets using randomized, placebo-controlled designs to confirm clinical efficacy and mechanisms of effect.

Transcendental meditation and hypothalamic-pituitary-adrenal axis functioning: a pilot, randomized controlled trial with young adults.

Transcendental meditation (TM) is effective in alleviating stress and anxiety and promoting well-being. While the underlying biological mechanisms of TM are not yet fully explored, the hypothalamic-pituitary-adrenal (HPA) axis represents an index providing important clues embodying the stress system cascade. In this pilot study, young adults were randomly assigned to TM training followed by 8 weeks of meditation practice or a wait-list control condition. TM was conducted over 8 weeks. Thirty-four young adult participants were randomized; 27 participants completed the HPA outcome assessments (41% male). To assess HPA axis functioning, salivary samples to assess cortisol awakening response (CAR) that were collected in the morning, both at baseline and at week-4. Salivary cortisol in the context of a social stressor using the Trier Social Stress Test (TSST) was collected at week-8. The results indicate that participants who were randomly assigned to TM had lower awakening salivary cortisol levels and a greater drop in CAR from baseline to week-4 than the control group. There were no significant differences in HPA axis functioning in the context of the TSST. Primary limitations of this randomized controlled trial were the small sample size, the use of a wait-list as opposed to an active control, and the limited scope of HPA axis assessments. The results of this pilot study provide tentative evidence that TM may impact biological stress system functioning and suggests that this may be a worthwhile avenue to continue to examine. It will also be useful to extend these findings to a broader array of meditative and mindful practices, particularly for those who are experiencing more distress.

Longitudinal Alterations in Prefrontal Resting Brain Connectivity in Non-Treatment-Seeking Young Adults With Cannabis Use Disorder.

Background: Cannabis is increasingly perceived as a harmless drug by recreational users, yet chronic use may impact brain changes into adulthood. Repeated cannabis exposure has been associated with enduring synaptic changes in executive control and reward networks. It is important to determine whether there are brain functional alterations within these networks in individuals that do not seek treatment for chronic cannabis abuse. Methods: This longitudinal study compared resting-state functional connectivity changes in executive control and reward networks between 23 non-treatment-seeking young adults with cannabis use disorder (6 females; baseline age M = 19.3 ± 1.18) and 21 age-matched controls (10 females; baseline age M = 19.4 ± 0.65) to determine group differences in the temporal trajectories of resting-state functional connectivity across a 2-year span. Results: Results showed i) significant increases in resting-state functional connectivity between the caudal anterior cingulate cortex and precentral and parietal regions over time in the control group, but not in the cannabis use disorder group, and ii) sustained lower resting-state functional connectivity of anterior cingulate cortex seeds with frontal and thalamic regions in the cannabis use disorder group vs. the age-matched controls. Resting-state functional connectivity strength was correlated with cannabis use patterns in the cannabis use disorder sample. Conclusion: Longitudinal alterations in intrinsic functional organization of executive control networks found in non-treatment-seeking young adults with cannabis use disorder (when compared to age-matched controls) may impact regulatory control over substance use behavior. Current findings were limited to examining executive control and reward networks seeded in ACC and NAcc, respectively. Future studies with larger sample sizes and enough power are needed to conduct exploratory analyses examining rsFC of other networks beyond those within the scope of the current study.

Methylation of FKBP5 and SLC6A4 in Relation to Treatment Response to Mindfulness Based Stress Reduction for Posttraumatic Stress Disorder.

Mindfulness Based Stress Reduction (MBSR) is an effective non-pharmacologic treatment for veterans with PTSD. Extensive work has identified epigenetic factors related to PTSD disease risk and pathophysiology, but how these factors influence treatment response is unclear. Serotonin signaling and hypothalamic-pituitary-adrenal (HPA) axis functioning may be perturbed in PTSD and are molecular pathways targeted by PTSD treatments. To identify potential biomarkers for treatment response, we utilized genomic DNA isolated from peripheral blood samples from veterans with PTSD who were responders (n = 11) or non-responders (n = 11) to MBSR as part of a clinical trial. We assessed methylation levels at CpG sites in regions of the serotonin transporter (SLC6A4) previously associated with expression and depression outcomes, as well as the Intron 7 region of the FK506 binding protein 5 (FKBP5) containing known glucocorticoid response elements suggested to regulate this gene. Selected subjects were matched across MBSR responder status by baseline symptoms, age, sex, current smoking status, and current antidepressant use. Percent methylation was compared between responders and non-responders at baseline (pre-MBSR treatment). Additionally, percent change in methylation from baseline to post-treatment was compared between responders and non-responders. There was a significant time x responder group interaction for methylation in FKBP5 intron 7 bin 2 [F (1, 19) = 7.492, p = 0.013] whereby responders had a decrease in methylation and non-responders had an increase in methylation from before to after treatment in this region. Analyses of the three CpG sites within bin 2 revealed a significant time x responder group interaction for CpG_35558513 [F (1, 19) = 5.551, p = 0.029] which resides in a known glucocorticoid response element (GRE). Decreases in FKBP5 methylation after treatment in responders as compared to increases in non-responders suggest that effective meditation intervention may be associated with stress-related pathways at the molecular level. These preliminary findings suggest that DNA methylation signatures within FKBP5 are potential indicators of response to meditation treatment in PTSD and require validation in larger cohorts.

Transcendental meditation for veterans with post-traumatic stress disorder.

OBJECTIVE: Transcendental Meditation (TM) is a mental technique using a mantra to facilitate meditation. TM has a potential for treating symptoms of posttraumatic stress disorder (PTSD), but its clinical efficacy remains to be clarified. This pilot study evaluated the acceptability, preliminary effectiveness, and neurophysiology of TM for veterans with PTSD. METHOD: Twenty-nine veterans (20.7% female) were recruited from a major medical center and enrolled in the study. TM instruction was provided by certified TM teachers from the Maharishi Foundation and consisted of 8 weeks of individual and group-based meditation instruction and practice. Outcomes were assessed at baseline, during treatment, posttreatment, and at 2-month follow-up, and included clinical interviews, self-report questionnaires, and electroencephalography (EEG) recorded during resting and meditation states. RESULTS: From baseline to posttreatment, participants reported reductions in PTSD symptoms, experiential avoidance, and depressive and somatic symptoms, as well as increases on measures of mindfulness and quality of life. Gains were either maintained or continued to improve through the 2-month follow-up. Compared to baseline, EEG spectral power increased in low-frequency bands (1-7 Hz) at posttreatment and follow-up and only during meditation states suggesting TM-specific changes in brain state associated with the intervention. CONCLUSIONS: TM appears to be an acceptable and effective treatment for veterans with PTSD that warrants further study regarding specific outcomes and beneficial changes in brain function. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Ferumoxytol-enhanced magnetic resonance imaging assessing inflammation after myocardial infarction.

OBJECTIVES: Macrophages play a central role in the cellular inflammatory response to myocardial infarction (MI) and predict subsequent clinical outcomes. We aimed to assess temporal changes in cellular inflammation and tissue oedema in patients with acute MI using ultrasmallsuperparamagnetic particles of iron oxide (USPIO)-enhanced MRI. METHODS: Thirty-one patients were recruited following acute MI and followed up for 3 months with repeated T2 and USPIO-enhanced T2*-mapping MRI. Regions of interest were categorised into infarct, peri-infarct and remote myocardial zones, and compared with control tissues. RESULTS: Following a single dose, USPIO enhancement was detected in the myocardium until 24 hours (p<0.0001). Histology confirmed colocalisation of iron and macrophages within the infarcted, but not the non-infarcted, myocardium. Following repeated doses, USPIO uptake in the infarct zone peaked at days 2-3, and greater USPIO uptake was detected in the infarct zone compared with remote myocardium until days 10-16 (p<0.05). In contrast, T2-defined myocardial oedema peaked at days 3-9 and remained increased in the infarct zone throughout the 3-month follow-up period (p<0.01). CONCLUSION: Myocardial macrophage activity can be detected using USPIO-enhanced MRI in the first 2 weeks following acute MI. This observed pattern of cellular inflammation is distinct, and provides complementary information to the more prolonged myocardial oedema detectable using T2 mapping. This imaging technique holds promise as a non-invasive method of assessing and monitoring myocardial cellular inflammation with potential application to diagnosis, risk stratification and assessment of novel anti-inflammatory therapeutic interventions. TRIAL REGISTRATION NUMBER: Trial registration number: 14663. Registered on UK Clinical Research Network (http://public.ukcrn.org.uk) and also ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02319278?term=DECIFER&rank=2).

Examining Burnout, Depression, and Self-Compassion in Veterans Affairs Mental Health Staff.

OBJECTIVES: Burnout, a state of emotional exhaustion associated with negative personal and occupational outcomes, is prevalent among healthcare providers. A better understanding of the psychological factors that may be associated with resilience to burnout is essential to develop effective interventions. Self-compassion, which includes kindness toward oneself, recognition of suffering as part of shared human experience, mindfulness, and nonjudgment toward inadequacies and failures, may be one such factor. The purpose of this study was to examine the relationships between burnout, depression, and self-compassion in Veterans Affairs (VA) mental health staff. DESIGN: Cross-sectional study. SETTING: VA medical center and affiliated community-based clinics. PARTICIPANTS: VA mental health staff. OUTCOME MEASURES: The 19-item Copenhagen Burnout Inventory, the 26-item Self-Compassion Scale, and the Patient Health Questionnaire 2-item depression screen. Demographic information included age, sex, years worked in current position, and number of staff supervised. RESULTS: One hundred and twenty-eight of a potential 379 individuals (33.8%) responded. Clerical support, nursing, social work, psychology, and psychiatry were the major professions represented. Self-compassion was inversely correlated with burnout (r = -0.41, p < 0.001), and inversely correlated with depression (rpb = -0.39, p < 0.001). The inverse relationship between self-compassion and burnout remained significant even after accounting for depressive symptoms and demographic variables in a multiple linear regression model. Of all the variables examined, self-compassion was the strongest predictor of burnout. CONCLUSIONS: The results of this study support the hypothesis that self-compassion may be associated with resilience to burnout. Alternatively, decreased self-compassion may be a downstream effect of increased burnout. Prospective, longitudinal studies are needed to determine the directional relationship between these factors, and whether interventions that cultivate self-compassion may decrease burnout and/or protect against its negative personal and professional outcomes.

Low-Intensity Transcranial Current Stimulation in Psychiatry.

Neurostimulation is rapidly emerging as an important treatment modality for psychiatric disorders. One of the fastest-growing and least-regulated approaches to noninvasive therapeutic stimulation involves the application of weak electrical currents. Widespread enthusiasm for low-intensity transcranial electrical current stimulation (tCS) is reflected by the recent surge in direct-to-consumer device marketing, do-it-yourself enthusiasm, and an escalating number of clinical trials. In the wake of this rapid growth, clinicians may lack sufficient information about tCS to inform their clinical practices. Interpretation of tCS clinical trial data is aided by familiarity with basic neurophysiological principles, potential mechanisms of action of tCS, and the complicated regulatory history governing tCS devices. A growing literature includes randomized controlled trials of tCS for major depression, schizophrenia, cognitive disorders, and substance use disorders. The relative ease of use and abundant access to tCS may represent a broad-reaching and important advance for future mental health care. Evidence supports application of one type of tCS, transcranial direct current stimulation (tDCS), for major depression. However, tDCS devices do not have regulatory approval for treating medical disorders, evidence is largely inconclusive for other therapeutic areas, and their use is associated with some physical and psychiatric risks. One unexpected finding to arise from this review is that the use of cranial electrotherapy stimulation devices-the only category of tCS devices cleared for use in psychiatric disorders-is supported by low-quality evidence.

Abnormal striatal resting-state functional connectivity in adolescents with obsessive-compulsive disorder.

Neuroimaging research has implicated abnormalities in cortico-striatal-thalamic-cortical (CSTC) circuitry in pediatric obsessive-compulsive disorder (OCD). In this study, resting-state functional magnetic resonance imaging (R-fMRI) was used to investigate functional connectivity in the CSTC circuitry in adolescents with OCD. Imaging was obtained with the Human Connectome Project (HCP) scanner using newly developed pulse sequences which allow for higher spatial and temporal resolution. Fifteen adolescents with OCD and 13 age- and gender-matched healthy controls (ages 12-19) underwent R-fMRI on the 3T HCP scanner. Twenty-four minutes of resting-state scans (two consecutive 12-min scans) were acquired. We investigated functional connectivity of the striatum using a seed-based, whole brain approach with anatomically-defined seeds placed in the bilateral caudate, putamen, and nucleus accumbens. Adolescents with OCD compared with controls exhibited significantly lower functional connectivity between the left putamen and a single cluster of right-sided cortical areas including parts of the orbitofrontal cortex, inferior frontal gyrus, insula, and operculum. Preliminary findings suggest that impaired striatal connectivity in adolescents with OCD in part falls within the predicted CSTC network, and also involves impaired connections between a key CSTC network region (i.e., putamen) and key regions in the salience network (i.e., insula/operculum). The relevance of impaired putamen-insula/operculum connectivity in OCD is discussed.

Supplementation with Quaternary Benzo(c)phenanthridine Alkaloids Decreased Salivary Cortisol and Salmonella Shedding in Pigs After Transportation to the Slaughterhouse.

The present study was aimed at evaluating the effect of herbal extracts supplementation, particularly quaternary-benzo(c)phenanthridine alkaloids (QBA), which have been previously demonstrated to have anti-inflammatory, antimicrobial, and immune-modulator effects. We investigated the role of QBA on stress response and Salmonella shedding in finishing pigs transported to the slaughterhouse. A total of 82 pigs were orally challenged with a Salmonella cocktail (day 0) containing Salmonella Meleagridis, Hartford, Bovismorbificans and Newport serovars and randomly assigned to three treatment groups after 2 wks (day [D] 14): T1, in-feed QBA; T2, in-feed and water-soluble QBA; CON, nonsupplemented). Pigs were transported to the slaughterhouse 2 weeks after intervention (D 28) and slaughtered after nearly 19 h (D 29). Saliva, fecal samples, and carcass swabs were collected from all pigs. Salivary cortisol, Salmonella shedding, and carcass contamination were measured. A high positive correlation (Spearman rank correlation coefficient range 0.82-0.93) between salivary cortisol and Salmonella shedding was found after transportation in all groups (p < 0.05). Only the CON group showed an increase in salivary cortisol after transportation (5.48 ng/mL; p < 0.0001) to concentrations that were higher than in T1 (2.73 ng/mL; p = 0.0002) and T2 (1.88 ng/mL; p < 0.0001). Salmonella prevalence and shedding decreased after transportation in pigs receiving the QBA intervention (p < 0.05), whereas the control group showed a significant increase in Salmonella shedding after transportation (p = 0.04). At D 28, pigs in T2 shed lower numbers of Salmonella as compared to T1 (1.3E + 02 CFU/mL versus 8E + 03 CFU/mL; p = 0.002). Additionally, carcass contamination by Salmonella was higher in the CON group than the treated groups (p = 0.01). The findings show QBA intervention was effective in reducing transportation stress of pigs, resulting in reduced Salmonella shedding and positively impacting animal welfare and pork safety.

Mindfulness-Based Stress Reduction for Posttraumatic Stress Disorder Among Veterans: A Randomized Clinical Trial.

IMPORTANCE: Mindfulness-based interventions may be acceptable to veterans who have poor adherence to existing evidence-based treatments for posttraumatic stress disorder (PTSD). OBJECTIVE: To compare mindfulness-based stress reduction with present-centered group therapy for treatment of PTSD. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of 116 veterans with PTSD recruited at the Minneapolis Veterans Affairs Medical Center from March 2012 to December 2013. Outcomes were assessed before, during, and after treatment and at 2-month follow-up. Data collection was completed on April 22, 2014. INTERVENTIONS: Participants were randomly assigned to receive mindfulness-based stress reduction therapy (n = 58), consisting of 9 sessions (8 weekly 2.5-hour group sessions and a daylong retreat) focused on teaching patients to attend to the present moment in a nonjudgmental, accepting manner; or present-centered group therapy (n = 58), an active-control condition consisting of 9 weekly 1.5-hour group sessions focused on current life problems. MAIN OUTCOMES AND MEASURES: The primary outcome, change in PTSD symptom severity over time, was assessed using the PTSD Checklist (range, 17-85; higher scores indicate greater severity; reduction of 10 or more considered a minimal clinically important difference) at baseline and weeks 3, 6, 9, and 17. Secondary outcomes included PTSD diagnosis and symptom severity assessed by independent evaluators using the Clinician-Administered PTSD Scale along with improvements in depressive symptoms, quality of life, and mindfulness. RESULTS: Participants in the mindfulness-based stress reduction group demonstrated greater improvement in self-reported PTSD symptom severity during treatment (change in mean PTSD Checklist scores from 63.6 to 55.7 vs 58.8 to 55.8 with present-centered group therapy; between-group difference, 4.95; 95% CI, 1.92-7.99; P=.002) and at 2-month follow-up (change in mean scores from 63.6 to 54.4 vs 58.8 to 56.0, respectively; difference, 6.44; 95% CI, 3.34-9.53, P < .001). Although participants in the mindfulness-based stress reduction group were more likely to show clinically significant improvement in self-reported PTSD symptom severity (48.9% vs 28.1% with present-centered group therapy; difference, 20.9%; 95% CI, 2.2%-39.5%; P = .03) at 2-month follow-up, they were no more likely to have loss of PTSD diagnosis (53.3% vs 47.3%, respectively; difference, 6.0%; 95% CI, -14.1% to 26.2%; P = .55). CONCLUSIONS AND RELEVANCE: Among veterans with PTSD, mindfulness-based stress reduction therapy, compared with present-centered group therapy, resulted in a greater decrease in PTSD symptom severity. However, the magnitude of the average improvement suggests a modest effect. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01548742.

Parietal lobe volume deficits in adolescents with schizophrenia and adolescents with cannabis use disorders.

OBJECTIVE: In early-onset schizophrenia (EOS), the earliest structural brain volumetric abnormalities appear in the parietal cortices. Early exposure to cannabis may represent an environmental risk factor for developing schizophrenia. This study characterized cerebral cortical gray matter structure in adolescents in regions of interest (ROIs) that have been implicated in EOS and cannabis use disorders (CUD). METHOD: T1-weighted magnetic resonance images were acquired from adolescents with EOS (n = 35), CUD (n = 16), EOS + CUD (n = 13), and healthy controls (HC) (n = 51). Using FreeSurfer, brain volume was examined within frontal, temporal, parietal and subcortical ROIs by a 2 (EOS versus no EOS) × 2 (CUD versus no CUD) design using multivariate analysis of covariance. In ROIs in which volumetric differences were identified, additional analyses of cortical thickness and surface area were conducted. RESULTS: A significant EOS-by-CUD interaction was observed. In the left superior parietal region, both "pure" EOS and "pure" CUD had smaller gray matter volumes that were associated with lower surface area compared with HC. A similar alteration was observed in the comorbid group compared with HC, but there was no additive volumetric deficit found in the comorbid group compared with the separate groups. In the left thalamus, the comorbid group had smaller gray matter volumes compared with the CUD and HC groups. CONCLUSIONS: These preliminary data indicate that the presence of a CUD may moderate the relationship between EOS and cerebral cortical gray matter structure in the left superior parietal lobe. Future research will follow this cohort over adolescence to further examine the impact of cannabis use on neurodevelopment.

Evaluation of a pharmacist-managed diabetes medication therapy adherence clinic / Evaluación de una clínica farmacéutica para el cumplimiento del tratamiento en diabetes

Patient adherence to prescribed medication regimens is important in diabetes care to prevent or delay microvascular and macrovascular complications such as retinopathy, nephropathy and myocardial infarction. In Penang Hospital, Malaysia, pharmacists collaborate with physicians in diabetes care through a pharmacist-managed Diabetes Medication Therapy Adherence Clinic (DMTAC) in the Endocrine Clinic, in operation since 2006. Objective: To evaluate the effectiveness of the pharmacist-managed DMTAC program in improving glycaemic control, lipid parameters and patients´ medication adherence. Method: A retrospective study among patients enrolled in the DMTAC program was conducted between September 2007 and December 2008. Data was included from patients with a glycosylated haemoglobin (HbA1c) >8% and who had completed eight visits with the pharmacists. Medical records and DMTAC forms that provided patients´ demographics, medication regimens, adherence and laboratory parameters as well as pharmacists´ interventions were reviewed. HbA1c, fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL), triglycerides (TG) and high-density lipoprotein cholesterol (HDL) were evaluated. Documented data of patients´ adherence to medication regimen [Modified Morisky Medication Adherence Score (MMMAS); high adherence if score >8, medium adherence if score 6 to <8 and low adherence if score <6] was also evaluated. Results: A total of 43 patients (53.5% females; 46.5% Malays, 44.2% Chinese and 9.3% Indians) were included in the analysis. A mean reduction in HbA1c of 1.73% (p<0.001), mean reduction in FBG of 2.65mmol/l (p=0.01) and mean reduction in LDL cholesterol of 0.38mmol/l (p=0.007) were achieved. The difference in TG and HDL cholesterol were not significant. Patients´ adherence to medication regimens improved significantly with an increase in the mean MMMAS score from 7.00 to 10.84 (p<0.001) after completion of the DMTAC program. Conclusion: The pharmacist-managed DMTAC program resulted in significant improvements in HbA1c, glucose and LDL cholesterol levels as well as medication adherence in patients with diabetes (AU)

El cumplimiento de la medicación en los pacientes diabéticos es importante para prevenir o retrasar complicaciones micro y macrovasculares tales como retinopatía, neuropatía e infarto de miocardio. En el Hospital de Penang, Malasia, los farmacéuticos colaboran con los médicos en diabetes a través de una clínica farmacéutica para el cumplimiento del tratamiento en diabetes (DMTAC) en la clínica endocrinológica, operando desde 2006. Objetivo: Evaluar la efectividad del programa de la DMTAC en la mejora del control glucémico, de parámetros lipídicos y de cumplimiento de la medicación por los pacientes. Métodos: Entre septiembre 2007 y diciembre 2008 se realizó un estudio retrospectivo entre los pacientes atendidos en el programa de la DMTAC. Se incluyeron datos de pacientes con hemoglobina glicosilada (HbA1c) >8% y que habían completado 8 visitas con el farmacéutico. Se revisaron los historiales médicos y los formularios de la DMTAC que proporcionaron datos demográficos de los pacientes, medicación, cumplimiento y parámetros de laboratorio, así como las intervenciones de los farmacéuticos. La HbA1c, glucemia en ayuno, colesterol de lipoproteínas de baja densidad (LDL), triglicéridos (TG) y colesterol de lipoproteínas de alta densidad (HDL). También se evaluaron los datos de cumplimiento de los pacientes [Modified Morisky Medication Adherence Score (MMMAS); alto cumplimiento si la puntuación >8, cumplimiento medio si puntuación de 6 a 8 y bajo cumplimiento si puntuación <6]. Resultados: Se incluyó en el análisis un total de 43 pacientes (53,5% mujeres; 46.5% Malayos, 44.2% Chinos and 9.3% Indios). Se obtuvo una reducción media de HbA1c de 1,73% (p<0,001), de glucemia de 2,65 mmol/l (p=0,01) y de colesterol LDL de 0.38 mmol/l (p=0,007). La diferencia en TG y colesterol HDL no fue significativa. Después de completar el programa de la DMTAC, el cumplimiento de los pacientes de su medicación mejoró significativamente con un aumento en la puntuación del MMMAS de 7,00 a 10,84 (p<0,001). Conclusión: el programa farmacéutico de la DMTAC produjo mejorías significativas en los niveles de HbA1c, glucosa y colesterol LDL, así como en el cumplimiento de la medicación de los pacientes con diabetes (AU)