On April 10, 2020, a treasured cell biologist and ardent champion of the Golgi complex passed away. This has caused deep sadness, and we seek to commemorate her remarkable scientific contributions, ...her warm and generous personality, and her endearing sense of humor.
Regulated exocytosis of synaptic vesicles is substantially faster than of endocrine dense core vesicles despite similar molecular machineries. The reasons for this difference are unknown and could be ...due to different regulatory proteins, different spatial arrangements, different vesicle sizes, or other factors. To address these questions, we take a reconstitution approach and compare regulated SNARE-mediated fusion of purified synaptic and dense core chromaffin and insulin vesicles using a single vesicle-supported membrane fusion assay. In all cases, Munc18 and complexin are required to restrict fusion in the absence of calcium. Calcium triggers fusion of all docked vesicles. Munc13 (C1C2MUN domain) is required for synaptic and enhanced insulin vesicle fusion, but not for chromaffin vesicles, correlating inversely with the presence of CAPS protein on purified vesicles. Striking disparities in calcium-triggered fusion rates are observed, increasing with curvature with time constants 0.23 s (synaptic vesicles), 3.3 s (chromaffin vesicles), and 9.1 s (insulin vesicles) and correlating with rate differences in cells.
Adults with inflammatory bowel disease (IBD) are at a greater risk of anxiety and depression and impaired quality of life (QoL) compared with healthy controls and other chronic physical illness ...groups. Consequently, the development and evaluation of well-defined and theoretically robust psychotherapeutic interventions for adults with IBD are desirable. To date, interventions have, for the most part, used multiple cross-theoretical approaches. Published reviews are heterogeneous in terms both of categorization of psychotherapeutic approaches and also of conclusions relating to efficacy. A recent Cochrane meta-analysis of randomized controlled trials found no evidence for the efficacy of these interventions in adults, as in a number of previous reviews, ideologically disparate interventions (e.g., psychodynamic and cognitive behavioral) were grouped together. We aimed to extend the currently available literature on psychological intervention in IBD by: evaluating the efficacy of specific strategies (i.e., stress management, psychodynamic, cognitive behavioral therapy, or hypnosis) in improving psychological symptoms and QoL, including all controlled and noncontrolled studies, and explicating the methodological problems in published trials. Sixteen studies (5 stress management, 4 psychodynamic, 5 cognitive behavioral therapy, and 2 hypnosis) were evaluated. Interventions predominantly based on stress management showed only modest benefits for IBD or mental health symptoms or QoL. Cognitive behavioral therapy studies showed generally consistent benefits in terms of anxiety and depression symptoms, but inconsistent outcomes regarding IBD symptoms. Psychodynamically informed interventions reduced depressive and anxiety symptoms, but not IBD severity. Both hypnosis studies, albeit using different methods, seemed to have a more positive impact on disease severity than mental health symptoms or QoL. Our results suggest that while further well-designed and evaluated interventions are needed, psychological input can make a positive contribution to best practice multidisciplinary treatment of adults with IBD.
Study objective Parenteral benzodiazepines or antipsychotics are often used to manage acute agitation in emergency department (ED) settings in which alternative strategies have failed or are not ...feasible. There are scant data comparing parenteral medication regimens. We aim to determine the efficacy and safety of intravenous droperidol or olanzapine as an adjunct to intravenous midazolam for rapid patient sedation. Methods We undertook a randomized, double-blind, placebo-controlled, double-dummy, clinical trial in 3 EDs (August 2009 to March 2011). Adult patients (n=336) requiring intravenous drug sedation for acute agitation were randomized to receive a saline solution (control), droperidol (5 mg), or olanzapine (5 mg) bolus. This was immediately followed by incremental intravenous midazolam boluses (2.5 to 5 mg) until sedation was achieved. The primary outcome was time to sedation. Secondary outcomes were need for “rescue” drugs and adverse events. Results Three hundred thirty-six patients were randomized to the 3 groups. Baseline characteristics were similar across groups. The differences in medians for times to sedation between the control and droperidol and control and olanzapine groups were 4 minutes (95% confidence interval CI 1 to 6 minutes) and 5 minutes (95% CI 1 to 6 minutes), respectively. At any point, patients in the droperidol and olanzapine groups were approximately 1.6 times more likely to be sedated compared with controls: droperidol and olanzapine group hazard ratios were 1.61 (95% CI 1.23 to 2.11) and 1.66 (95% CI 1.27 to 2.17), respectively. Patients in the droperidol and olanzapine groups required less rescue or alternative drug use after initial sedation. The 3 groups' adverse event profiles and lengths of stay did not differ. Conclusion Intravenous droperidol or olanzapine as an adjunct to midazolam is effective and decreases the time to adequate sedation compared with midazolam alone.
Objective
This study evaluated the severity ratings for anorexia nervosa (AN) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) and an alternative severity ...rating based on overvaluation of weight/shape, on a range of psychological and biological variables.
Method
A sample of 312 treatment‐seeking patients with AN (mean age = 25.3, SD = 7.6; mean BMI = 16.8 kg/m2, SD = 2.4) were categorised using both DSM‐5 severity levels (mild/moderate/severe/extreme) and weight/shape (low/high) overvaluation. The severity categories were compared on a range of psychological (e.g., eating psychopathology) and biological (e.g., sodium) variables.
Results
Results showed that the overvaluation of weight/shape appeared better at indexing the level of severity in psychological variables among patients with AN compared to the DSM‐5 severity rating with moderate to large effect sizes. Moreover, the DSM‐5 mild and moderate severity groups experienced significantly higher eating and general psychopathology than the severe and extreme groups. Finally, neither the DSM‐5 nor the weight/shape severity groups differed on any of the biological variables.
Conclusions
This study provided no support for the DSM‐5 severity rating for AN, while initial support was found for the weight/shape overvaluation approach in indexing psychological but not biological correlates.
Highlights
This study assessed both the Diagnostic and Statistical Manual of Mental Disorders‐5 (DSM‐5) and the alternative severity indices for anorexia nervosa (AN) using overvaluation of weight and shape on a range of psychological (e.g., eating psychopathology) and biological (e.g., sodium, potassium level) correlates.
Overvaluation of weight/shape appeared to be better at indexing the level of severity in psychological variables among patients with AN compared to the DSM‐5 severity rating with moderate to large effect sizes.
Neither the DSM‐5 nor the weight/shape severity groups were able to index the level of severity in biological variables.
Microtubule-targeting agents (MTAs), widely used as biological probes and chemotherapeutic drugs, bind directly to tubulin subunits and "kinetically stabilize" microtubules, suppressing the ...characteristic self-assembly process of dynamic instability. However, the molecular-level mechanisms of kinetic stabilization are unclear, and the fundamental thermodynamic and kinetic requirements for dynamic instability and its elimination by MTAs have yet to be defined. Here we integrate a computational model for microtubule assembly with nanometer-scale fluorescence microscopy measurements to identify the kinetic and thermodynamic basis of kinetic stabilization by the MTAs paclitaxel, an assembly promoter, and vinblastine, a disassembly promoter. We identify two distinct modes of kinetic stabilization in live cells, one that truly suppresses on-off kinetics, characteristic of vinblastine, and the other a "pseudo" kinetic stabilization, characteristic of paclitaxel, that nearly eliminates the energy difference between the GTP- and GDP-tubulin thermodynamic states. By either mechanism, the main effect of both MTAs is to effectively stabilize the microtubule against disassembly in the absence of a robust GTP cap.
DSM-5 contains substantial changes to eating disorder diagnoses. We examined relative prevalence rates of DSM-IV and DSM-5 eating disorder diagnoses using Eating Disorder Examination-Questionnaire ...diagnostic algorithms in 117 community out-patients. DSM-5 criteria produced a reduction in combined 'other specified feeding or eating disorder' and 'unspecified feeding or eating disorder' from 46% to 29%, an increase in anorexia nervosa diagnoses from 35% to 47%, the same number of bulimia nervosa diagnoses and a 5% rate of binge eating disorder diagnoses.
Childhood maltreatment and trauma may be risk factors for the development of body dysmorphic disorder (BDD). However, the limited research to date on these topics has been constrained by either the ...absence of a matched healthy control group or non-comprehensive assessments.
This study assessed the prevalence and severity of childhood maltreatment and other traumatic events in 52 BDD participants (56% female) and 57 matched controls (51% female) with no history of mental illness, using the Childhood Trauma Questionnaire and a checklist assessing broader traumatic events.
In comparison with controls, participants with BDD showed a higher prevalence of emotional abuse (61.5% vs. 33.3%) and physical neglect (59.6% vs. 28.1%), as well as more severe overall maltreatment, emotional abuse, and emotional and physical neglect. BDD participants were also more likely to meet cut-offs for multiple types of maltreatment and reported an elevated number and variety of broader traumatic childhood events (e.g., life-threatening illness). In BDD, increasingly severe maltreatment was correlated with greater severity of BDD symptoms, anxiety and suicidal ideation.
These data suggest that childhood maltreatment and exposure to other traumatic events are common and severe in BDD and are cross-sectionally associated with the severity of clinical symptoms. Adversity linked to maladaptive family functioning during childhood may therefore be especially relevant to people with BDD and could relate to social and emotional processing problems in the disorder.
•BDD participants report more prevalent and severe childhood adversity than controls.•Emotional abuse and physical neglect were especially common in BDD participants.•Childhood maltreatment was correlated with more severe psychopathology in BDD.•Childhood adversity may have long-term associations with BDD development.
The authors reviewed the literature on psychological and psychosocial outcomes for individuals undergoing cosmetic surgery, to address whether elective cosmetic procedures improve psychological ...well-being and psychosocial functioning and whether there are identifiable predictors of an unsatisfactory psychological outcome. They conducted a search of appropriate computerized databases for studies that evaluated psychological and psychosocial status both before and after elective cosmetic surgery. They identified 37 relevant studies of varying cosmetic procedures that utilized disparate methodologies. Overall, patients appeared generally satisfied with the outcome of their procedures, although some exhibited transient and some exhibited longer-lasting psychological disturbance. Factors associated with poor psychosocial outcome included being young, being male, having unrealistic expectations of the procedure, previous unsatisfactory cosmetic surgery, minimal deformity, motivation based on relationship issues, and a history of depression, anxiety, or personality disorder. Body dysmorphic disorder was also recognized by some studies as a predictor of poor outcome, a finding reinforced by reference to the psychiatric literature. The authors conclude that although most people appear satisfied with the outcome of cosmetic surgical procedures, some are not, and attempts should be made to screen for such individuals in cosmetic surgery settings.
The efficacy of acceptance and commitment therapy (ACT) in psychosis has been reported but not for medication-resistant psychosis.
To test the efficacy of ACT in a sample of community-residing ...patients with persisting psychotic symptoms. (Australian New Zealand Clinical Trials Registry: ACTRN12608000210370.) METHOD: The primary outcome was overall mental state at post-therapy (Positive and Negative Syndrome Scale - total); secondary outcomes were psychotic symptom dimensions and functioning. In total, 96 patients were randomised to ACT (n = 49) or befriending (n = 47). Symptom, functioning and process measures were administered at baseline, post-therapy and 6 months later.
There was no group difference on overall mental state. In secondary analyses the ACT group showed greater improvement in positive symptoms and hallucination distress at follow-up: Cohen's d = 0.52 (95% CI 0.07-0.98) and 0.65 (95% CI 0.24-1.06), respectively.
Improvements reflected the treatment focus on positive symptoms; however, absence of process-measure changes suggests that the ACT intervention used did not manipulate targeted processes beyond befriending. Symptom-specific therapy refinements, improved investigation of process and attention to cognitive functioning and dose are warranted in future research.
PDF
