The effects of acute serotonin challenge on executive planning in patients with obsessive-compulsive disorder (OCD), their first-degree relatives, and healthy controls

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s00213-020-05597-7.Rationale: OCD is characterized by executive function impairment and by clinical responsivity to selective serotonin reuptake inhibitors (SSRIs). Executive planning deficits constitute a candidate endophenotype for OCD. It is not known whether this endophenotype is responsive to acute serotonin manipulation. Objective: To investigate the effects of acute SSRI administration on executive function in patients with OCD, first-degree relatives of patients with OCD and healthy controls. Methods: A randomized double-blind crossover study assessed the effects of single dose escitalopram (20mg) and placebo on executive planning in 24 patients with OCD, 13 clinically unaffected first-degree relatives of patients with OCD and 28 healthy controls. Performance on a Tower of London task measuring executive planning was assessed 4 hours after oral administration of the pharmacological challenge / placebo, and compared across and within groups using a mixed model ANOVA. Results: On the outcome measure of interest, i.e. the mean number of choices to obtain the correct solution, there was a marginally significant effect of group (F(2, 59)=3.1; p=0.052), with patients (Least square [LS] mean: 1.43; Standard Error [SE]: 0.06; 95% confidence interval [CI], 1.31-1.55) and their relatives (LS mean: 1.46; SE: 0.08; 95% CI, 1.30-1.62) performing worse than matched healthy controls (LS mean: 1.26; SE: 0.05; 95% CI, 1.15-1.37) on placebo. There was a trend towards a significant group x treatment interaction (F(2, 58)=2.8, p=0.069), with post hoc tests showing (i) patients (p=0.009; LS mean difference: 0.23; SE: 0.08) and relatives (p=0.03; LS mean difference: 0.22; SE: 0.10) were more impaired compared to controls and (ii) escitalopram was associated with improved executive planning in patients with OCD (p=0.013; LS mean difference: 0.1; SE: 0.04), but not other groups (both p>0.1; controls: LS mean difference: -0.03; SE: 0.04; relatives: LS mean difference: 0.02; SE: 0.05). Conclusion: Our findings are consistent with a view that there is impaired executive planning in OCD, and that this constitutes a behavioral endophenotype. In patients with OCD, but not in relatives, acute SSRI administration ameliorated this deficit. Further investigation is needed to understand common and differential involvement of neurochemical systems in patients with OCD and their relatives.Peer reviewe

Piccolo genotype modulates neural correlates of emotion processing but not executive functioning

Major depressive disorder (MDD) is characterized by affective symptoms and cognitive impairments, which have been associated with changes in limbic and prefrontal activity as well as with monoaminergic neurotransmission. A genome-wide association study implicated the polymorphism rs2522833 in the piccolo (PCLO) gene—involved in monoaminergic neurotransmission—as a risk factor for MDD. However, the role of the PCLO risk allele in emotion processing and executive function or its effect on their neural substrate has never been studied. We used functional magnetic resonance imaging (fMRI) to investigate PCLO risk allele carriers vs noncarriers during an emotional face processing task and a visuospatial planning task in 159 current MDD patients and healthy controls. In PCLO risk allele carriers, we found increased activity in the left amygdala during processing of angry and sad faces compared with noncarriers, independent of psychopathological status. During processing of fearful faces, the PCLO risk allele was associated with increased amygdala activation in MDD patients only. During the visuospatial planning task, we found no genotype effect on performance or on BOLD signal in our predefined areas as a function of increasing task load. The PCLO risk allele was found to be specifically associated with altered emotion processing, but not with executive dysfunction. Moreover, the PCLO risk allele appears to modulate amygdala function during fearful facial processing in MDD and may constitute a possible link between genotype and susceptibility for depression via altered processing of fearful stimuli. The current results may therefore aid in better understanding underlying neurobiological mechanisms in MDD

Evaluation of strain and stress states in the single point incremental forming process

Single point incremental forming (SPIF) is a promising manufacturing process suitable for small batch production. Furthermore, the material formability is enhanced in comparison with the conventional sheet metal forming processes, resulting from the small plastic zone and the incremental nature. Nevertheless, the further development of the SPIF process requires the full understanding of the material deformation mechanism, which is of great importance for the effective process optimization. In this study, a comprehensive finite element model has been developed to analyse the state of strain and stress in the vicinity of the contact area, where the plastic deformation increases by means of the forming tool action. The numerical model is firstly validated with experimental results from a simple truncated cone of AA7075-O aluminium alloy, namely, the forming force evolution, the final thickness and the plastic strain distributions. In order to evaluate accurately the through-thickness gradients, the blank is modelled with solid finite elements. The small contact area between the forming tool and the sheet produces a negative mean stress under the tool, postponing the ductile fracture occurrence. On the other hand, the residual stresses in both circumferential and meridional directions are positive in the inner skin of the cone and negative in the outer skin. They arise predominantly along the circumferential direction due to the geometrical restrictions in this direction.The authors would like to gratefully acknowledge the financial support from the Portuguese Foundation for Science and Technology (FCT) under project PTDC/EMS-TEC/1805/2012. The first author is also grateful to the FCT for the postdoctoral grant SFRH/BPD/101334/2014.info:eu-repo/semantics/publishedVersio

Bacterial cellulose production by Gluconacetobacter xylinus by employing alternative culture media

Bacterial cellulose (BC) is used in different fields as a biological material due to its unique properties. Despite there being many BC applications, there still remain many problems associated with bioprocess technology, such as increasing productivity and decreasing production cost. New technologies that use waste from the food industry as raw materials for culture media promote economic advantages because they reduce environmental pollution and stimulate new research for science sustainability. For this reason, BC production requires optimized conditions to increase its application. The main objective of this study was to evaluate BC production by Gluconacetobacter xylinus using industry waste, namely, rotten fruits and milk whey, as culture media. Furthermore, the structure of BC produced at different conditions was also determined. The culture media employed in this study were composed of rotten fruit collected from the disposal of free markets, milk whey from a local industrial disposal, and their combination, and Hestrin and Schramm media was used as standard culture media. Although all culture media studied produced BC, the highest BC yield60 mg/mLwas achieved with the rotten fruit culture. Thus, the results showed that rotten fruit can be used for BC production. This culture media can be considered as a profitable alternative to generate high-value products. In addition, it combines environmental concern with sustainable processes that can promote also the reduction of production cost.The authors would like to acknowledge the Brazil National Council of Technological and Scientific Development (CNPq, FAPESP, and CAPES), the financial support from FAPESP 2009/14897-7, and Fundacao para a Ciencia e a Tecnologia (FCT)/Portugal through the project PTDC/EBB-EBI/112170/2009 for the financial support and scholarship. Special thanks to Talita Almeida Vicentin for technical support

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

ICAR: endoscopic skull‐base surgery

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