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Near-infrared (NIR) controlled drug delivery systems have drawn a lot of attention throughout the past few decades due to the deep penetration depth and comparatively minor side effects of the stimulus. In this study, we introduce an innovative approach for gastric cancer treatment by combining photothermal infrared-sensitive gold nanorods (AuNRs) with a conjugated microporous polymer (CMP) to create a drug delivery system tailored for transporting the cytostatic drug 5-fluorouracil (5-FU). CMPs are fully conjugated networks with high internal surface areas that can be precisely tailored to the adsorption and transport of active compounds through the right choice of chemical functionalities. By incorporation of surfactant-stabilized AuNRs into the CMP synthesis in dimethylformamide (DMF) the surfactant shell is destabilized and subsequently replaced by the CMP. Particularly, low initial surfactant concentrations led to uniform distribution of the AuNRs in the polymer matrix. Importantly, the integrated AuNRs maintain their plasmonic properties, as was confirmed via electron energy loss spectroscopy. Therefore, the significant photothermal properties are translated to the hybrid material as shown in a proof-of-principle experiment. Further, in an approximated gastric environment, 5-FU release studies were conducted with and without NIR stimulus. Thereby it was observed that increased Brownian motion due to the NIR irradiation not only accelerates the release but also increases the total released amount by influencing the adsorption-desorption equilibrium. This remarkable level of control of the release process underlines the immense potential of this hybrid material for precise and targeted drug delivery.

Background: The surgical management of complicated diverticulitis varies across Europe. EAES members prioritized this topic to be addressed by a clinical practice guideline through an online questionnaire., Objective: To develop evidence-informed clinical practice recommendations for key stakeholders involved in the treatment of complicated diverticulitis; to improve operative and perioperative outcomes, patient experience and quality of life through a systematic evidence-to-decision approach by a diverse, multidisciplinary panel., Methods: Informed by a linked individual participant data network meta-analysis of resection and primary anastomosis (PRA) versus Hartmann's resection (HR) versus laparoscopic lavage (LPL), a panel of general and colorectal surgeons, patient partners, trialists, and fellows appraised the certainty of the evidence using GRADE and CINeMA. The panel discussed the evidence using the evidence-to-decision framework during a synchronous consensus meeting. An asynchronous modified Delphi survey was used to establish consensus., Results: The panel suggests that patients with complicated diverticulitis without sepsis receive PRA over HR or LPL when there is availability of a surgeon with skills and experience in colorectal surgery. HR is suggested over PRA or LPL in the subgroups of septic, frail, as well as immunocompromised patients. These recommendations apply to patients with an indication for surgery. Surgeons and patients should first consider conditionally recommended interventions, then conditionally recommended against. Based on the evidence, the key benefit of PRA was a higher likelihood of not having a stoma at 1 year, with similar risks across comparisons. Conditional recommendations call for shared decision-making when considering management options. The full guideline with user-friendly decision aids is available in https://app.magicapp.org/#/guideline/7490 ., Conclusion: This clinical practice guideline provides evidence-informed recommendations on the management of patients with complicated diverticulitis in accordance with the highest methodological standards through a structured framework informed by an international, multidisciplinary panel of stakeholders., Competing Interests: Declarations. Disclaimers: This clinical practice guideline has been developed under the auspice of the European Association for Endoscopic Surgery (EAES). It is intended to be used primarily by health professionals (e.g., surgeons, anesthetists, physicians) and to assist in making informed clinical decisions on diagnostic measures and therapeutic management. It is also intended to inform individual practice of allied health professionals (e.g., surgical nurses, dieticians, physical rehabilitation therapists, psychologists); to inform strategic planning and resource management by health care authorities (e.g., regional and national authorities, health care institutions, hospital administration authorities); and to inform patients wishing to obtain an overview of the condition of interest and its management. The use of recommendations contained herein must be informed by supporting evidence accompanying each recommendation and by research evidence that might not have been published by the time of writing the present document. Users must thus base their actions informed by newly published evidence at any given point in time. The information in the guideline should not be relied upon as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. With the rapid development of scientific knowledge, new evidence may emerge between the time the guideline is developed and when it is published or read. The guideline is not continually updated and may not reflect the most recent evidence. The guideline addresses only the topics specifically identified therein and is not applicable to other interventions, diseases, or stages of diseases. This guideline does not mandate any particular course of medical care. Further, the guideline is not intended to substitute the independent professional judgment of the treating provider, as the guideline does not necessarily account for individual variation among patients. Even if evidence on a topic suggests a specific diagnostic and/or treatment action, users and especially health professionals may need to decide against the suggested or recommended action in view of circumstances related to patient values, preferences, co-morbidities and disease characteristics; available human, financial and material resources; and healthcare infrastructures. EAES provides this guideline on an “as is” basis, and makes no warranty, express or implied, regarding the guideline. Disclosures: Stavros A. Antoniou, Bright Huo, Monica Ortenzi, Roi Anteby, Yegor Tryliskyy, Francesco Maria Carrano, Georgios Seitidis, Dimitris Mavridis, Vincent T. Hoek, Alberto Serventi, Willem A. Bemelman, Gian Andrea Binda, Rafael Duran, Triantafyllos Doulias, Nauzer Forbes, Nader K. Francis, Fabian Grass, Jesper Jensen, Marianne Krogsgaard, Lisa H. Massey, Luca Morelli, Christian E. Oberkofler, Dorin E. Popa, Johannes Kurt Schultz, Shahnaz Sultan, Jean-Jacques Tuech, and Hendrik Jaap Bonjer declare no direct conflicts of interest related to this work. Indirect conflicts of external advisors were documented and managed as per Guidelines International Network Standards. Detailed conflict of interest statements of all contributors can be found in the online appendix [15]. A patient version of this guideline is available in Supplementary File 2. Ethics approval: Not applicable. Consent to participate: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The epileptogenic network in temporal lobe epilepsy (TLE) contains structures of the primary and secondary olfactory cortex such as the piriform and entorhinal cortex, the amygdala, and the hippocampus. Olfactory auras and olfactory dysfunction are relevant symptoms of TLE. This study aims to characterize olfactory function in TLE using olfactory testing and olfactory functional magnetic resonance imaging (fMRI). We prospectively enrolled 20 individuals with unilateral TLE (age 45 ± 20 years [mean ± SD], 65% female, 90% right-handed) and 20 healthy individuals (age 33 ± 15 years [mean ± SD], 35% female, 90% right-handed). In the TLE group, the presumed seizure onset zone was left-sided in 75%; in 45% of the individuals with TLE limbic encephalitis was the presumed etiology; and 15% of the individuals with TLE reported olfactory auras. Olfactory function was assessed with a Screening Sniffin' Sticks Test (Burkhart, Wedel, Germany) during a pre-assessment. During a pre-testing, all individuals were asked to rate the intensity, valence, familiarity, and associated memory of five different odors (eugenol, vanillin, phenethyl alcohol, decanoic acid, valeric acid) and a control solution. During the fMRI experiment, all individuals repeatedly smelled eugenol (positively valenced odor), valeric acid (negatively valenced odor), and the control solution and were asked to rate odor intensity on a five-point Likert scale. We acquired functional EPI sequences and structural images (T1, T2, FLAIR). Compared to healthy individuals, individuals with TLE rated the presented odors as more neutral (two-sided Mann-Whitney U tests, FDR-p < 0.05) and less familiar (two-sided Mann-Whitney U tests, FDR-p < 0.05). fMRI data analysis revealed a reduced response contrast in secondary olfactory areas (e.g., hippocampus) connected to the limbic system when comparing eugenol and valeric acid in individuals with TLE when compared with healthy individuals. However, no lateralization effect was obtained when calculating a lateralization index by the number of activated voxels in the olfactory system (two-sided Mann-Whitney U test; U = 176.0; p = 0.525). TLE is characterized by olfactory dysfunction and associated with hypoactivation of secondary olfactory structures connected to the limbic system. These findings contribute to our understanding of the pathophysiology of TLE. This study was preregistered on OSF Registries (www.osf.io)., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Aphantasia refers to reduced or absent visual imagery. While most of us can readily recall decade-old personal experiences (autobiographical memories, AM) with vivid mental images, there is a dearth of information about whether the loss of visual imagery in aphantasics affects their AM retrieval. The hippocampus is thought to be a crucial hub in a brain-wide network underlying AM. One important question is whether this network, especially the connectivity of the hippocampus, is altered in aphantasia. In the current study, we tested 14 congenital aphantasics and 16 demographically matched controls in an AM fMRI task to investigate how key brain regions (i.e. hippocampus and visual-perceptual cortices) interact with each other during AM re-experiencing. All participants were interviewed regarding their autobiographical memory to examine their episodic and semantic recall of specific events. Aphantasics reported more difficulties in recalling AM, were less confident about their memories, and described less internal and emotional details than controls. Neurally, aphantasics displayed decreased hippocampal and increased visual-perceptual cortex activation during AM retrieval compared to controls. In addition, controls showed strong negative functional connectivity between the hippocampus and the visual cortex during AM and resting-state functional connectivity between these two brain structures predicted better visualization skills. Our results indicate that visual mental imagery plays an important role in detail-rich vivid AM, and that this type of cognitive function is supported by the functional connection between the hippocampus and the visual-perceptual cortex., Competing Interests: MM, PL, TL, JS, SB, MR, CM No competing interests declared, (© 2024, Monzel, Leelaarporn et al.)

Background: Radiotherapy reduces local recurrence in locally advanced rectal cancer, but may cause harm in patients who do not experience recurrence. The aim was to investigate the impact of radiotherapy on long-term quality of life after curative treatment for rectal cancer, i.e. in patients without a recurrence during the follow-up., Methods: All patients operated on for rectal cancer in Norway under 75 years of age between 30 September 2007 and 1 October 2020 were identified using the Cancer Registry of Norway. Exclusion criteria were distant metastasis, recurrence and dementia. The primary outcome measure was the Gastrointestinal Quality of Life Index. Secondary outcome measures included the 36-item Short Form Survey. Inverse probability weights based on a multiple logistic regression model were used to balance prechosen covariates between the radiotherapy and no radiotherapy groups when assessing differences in outcomes., Results: Of 5014 invited patients, 2142 (43%) eligible patients answered the questionnaires. Of these 762 (36%) were treated with neoadjuvant radiotherapy plus surgery and 1380 (64%) with surgery alone. The mean follow-up time was 6.4 and 7.4 years respectively. After propensity score matching, the Gastrointestinal Quality of Life Index differed significantly between irradiated and non-irradiated patients ((mean(s.d.), mean score 103.8(19.4) versus 110.8(19.6) respectively, mean difference: -6.96 (95% c.i. -8.72 to -5.19); P < 0.001). Among patients without a stoma the mean difference was -8.1 points, whereas it was -5.7 for patients with a stoma. The radiotherapy group also scored significantly lower in 7 of 8 36-item Short Form Survey domains compared with the surgery alone group., Conclusion: Long-term quality of life was significantly lower in patients without a recurrence during the follow-up who received radiotherapy compared with patients who did not. These findings warrant a critical re-evaluation of the use of radiotherapy both in traditional neoadjuvant treatment and in modern organ-preserving treatment regimens., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: Stage III colon cancer is routinely treated with adjuvant chemotherapy, which causes significant short-term morbidity. Its effect on long-term quality of life (QoL) is poorly investigated. The aim of this study was to investigate long-term QoL after curative treatment for colon cancer and explore the impact of chemotherapy on general and disease-specific QoL., Method: All patients aged under 75 years operated on for colon cancer between 30 September 2007 and 1 October 2019 were identified by the Cancer Registry of Norway. Exclusion criteria were distant metastasis, recurrence, dementia and rectal/rectosigmoid cancer operation. The primary outcome measure was Gastrointestinal Quality of Life Index (GIQLI). Secondary outcome measures included the Short Form Health Survey (SF-36). To achieve balanced groups when assessing differences in outcome measures the analyses were weighted by inverse probability weights based on a multiple logistic regression model with prechosen confounders., Results: A total of 8627 patients were invited and 3109 responded (36% response rate). After exclusions 3025 patients were included, of whom 1148 (38%) had received adjuvant chemotherapy and 1877 (62%) had surgery alone, with mean follow-up of 75.5 versus 74.5 months, respectively. The GIQLI differed significantly between the groups [mean 111.0 (SD 18.4) vs. 115.6 (SD 17.8), respectively; mean difference: -4.6 (95% CI -5.9; -3.2); p < 0.001]. Those with the highest neurotoxicity exhibited the lowest GIQLI. The adjuvant chemotherapy group scored significantly lower in six of eight SF-36 domains compared with the surgery alone group. The main differences were found in social, physical and emotional function., Conclusion: Long-term QoL was significantly lower in patients who received adjuvant chemotherapy than in patients who did not. Neurotoxicity was closely related to reduced QoL in these patients. The low response rate limits the generalizability of the results., (© 2023 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Introduction: Loneliness poses a significant health problem and existing psychological interventions have shown only limited positive effects on loneliness. Based on preliminary evidence for impaired oxytocin signaling in trait-like loneliness, the current proof-of-concept study used a randomized, double-blind, placebo-controlled design to probe intranasal oxytocin (OT) as an adjunct to a short-term modular-based group intervention for individuals suffering from high trait-like loneliness (HL, UCLA Loneliness Scale ≥55)., Methods: Seventy-eight healthy HL adults (56 women) received five weekly group psychotherapy sessions. HL participants received OT or placebo before the intervention sessions. Primary outcomes were trait-like loneliness measured at baseline, after the intervention, and again at two follow-up time points (3 weeks and 3 months), and, assessed at each session, state loneliness (visual analog scale), perceived stress (Perceived Stress Scale, PSS-10), quality of life (World Health Organization Five Well-Being Index, WHO-5), and the therapeutic relationship (Group Questionnaire, GQ-D)., Results: The psychological intervention was associated with significantly reduced perceived stress and improved trait-like loneliness across treatment groups, which was still evident at the 3-month follow-up. OT had no significant effect on trait-like loneliness, quality of life, or perceived stress. However, compared to placebo, OT significantly facilitated the decrease in state loneliness within sessions and significantly improved positive bonding between the group members., Conclusion: Despite significantly improved trait-like loneliness after the intervention, OT did not significantly augment this effect. Further studies are needed to determine optimal intervention designs to translate the observed acute effects of OT into long-term benefits., (© 2024 S. Karger AG, Basel.)

Schizophrenia is associated with various deficits in social cognition that remain relatively unaltered by antipsychotic treatment. While faulty glutamate signaling has been associated with general cognitive deficits as well as negative symptoms of schizophrenia, no direct link between manipulation of glutamate signaling and deficits in mentalizing has been demonstrated thus far. Here, we experimentally investigated whether ketamine, an uncompetitive N-methyl-D-aspartate receptor antagonist known to induce psychotomimetic effects, influences mentalizing and its neural correlates. In a randomized, placebo-controlled between-subjects experiment, we intravenously administered ketamine or placebo to healthy participants performing a video-based social cognition task during functional magnetic resonance imaging. Psychotomimetic effects of ketamine were assessed using the Positive and Negative Syndrome Scale. Compared to placebo, ketamine led to significantly more psychotic symptoms and reduced mentalizing performance (more "no mentalizing" errors). Ketamine also influenced blood oxygen level dependent (BOLD) response during mentalizing compared to placebo. Specifically, ketamine increased BOLD in right posterior superior temporal sulcus (pSTS) and increased connectivity between pSTS and anterior precuneus. These increases may reflect a dysfunctional shift of attention induced by ketamine that leads to mentalizing deficits. Our findings show that a psychotomimetic dose of ketamine impairs mentalizing and influences its neural correlates, a result compatible with the notion that deficient glutamate signaling may contribute to deficits in mentalizing in schizophrenia. The results also support efforts to seek novel psychopharmacological treatments for psychosis and schizophrenia targeting glutamatergic transmission., (© 2023. Springer Nature Limited.)

Background: The Scandinavian Diverticulitis (SCANDIV) trial and the LOLA arm of the LADIES trial randomized patients with Hinchey III perforated diverticulitis to laparoscopic peritoneal lavage or sigmoid resection. The aim of this analysis was to identify risk factors for treatment failure in patients with Hinchey III perforated diverticulitis., Methods: This was a post hoc analysis of the SCANDIV trial and LOLA arm. Treatment failure was defined as morbidity requiring general anaesthesia (Clavien-Dindo grade IIIb or higher) within 90 days. Age, sex, BMI, ASA fitness grade, smoking status, previous episodes of diverticulitis, previous abdominal surgery, time to surgery, and surgical competence were all tested in univariable and multivariable logistic regression analyses using an interaction variable., Results: The pooled analysis included 222 patients randomized to laparoscopic lavage and primary resection (116 and 106 patients respectively). Univariable analysis found ASA grade to be associated with advanced morbidity in both groups, and the following factors in the laparoscopic lavage group: smoking, corticosteroid use, and BMI. Significant factors for laparoscopic lavage morbidity in multivariable analysis were smoking (OR 7.05, 95 per cent c.i. 2.07 to 23.98; P = 0.002) and corticosteroid use (OR 6.02, 1.54 to 23.51; P = 0.010)., Conclusion: Active smoking status and corticosteroid use were risk factors for laparoscopic lavage treatment failure (advanced morbidity) in patients with perforated diverticulitis., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

Introduction: Nutrition claims are one of the most common tools used to improve food decisions. Previous research has shown that nutrition claims impact expectations; however, their effects on perceived pleasantness, valuation, and their neural correlates are not well understood. These claims may have both intended and unintended effects on food perception and valuation, which may compromise their effect on food decisions., Methods: We investigated the effects of nutrition claims on expectations, perceptions, and valuation of milk-mix drinks in a behavioral (n = 110) and an fMRI (n = 39) study. In the behavioral study, we assessed the effects of a "fat-reduced" and a "protein-rich" nutrition claim on expected and perceived food attributes of otherwise equal food products. In the fMRI study, we investigated the effect of a "protein-rich" claim on taste pleasantness perception and valuation, and on their neural correlates during tasting and swallowing., Results: We found that both nutrition claims increased expected and perceived healthiness and decreased expected but not perceived taste pleasantness. The "protein-rich" claim increased expected but not perceived satiating quality ratings, while the "fat-reduced" claim decreased both expected and perceived satiating quality ratings. In the absence vs. presence of the "protein-rich" claim, we observed an increased activity in a cluster extending to the left nucleus accumbens during tasting and an increased functional connectivity between this cluster and a cluster in right middle frontal gyrus during swallowing., Conclusion: Altogether, we found that nutrition claims impacted expectations and attenuated reward-related responses during tasting but did not negatively affect perceived pleasantness. Our findings support highlighting the presence of nutrients with positive associations and exposure to foods with nutrition claims to increase their acceptance. Our study offers insights that may be valuable in designing and optimizing the use of nutrition claims., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

To survive, all animals need to predict what other agents are going to do next. We review neural mechanisms involved in the steps required for this ability. The first step is to determine whether an object is an agent, and if so, how sophisticated it is. This involves brain regions carrying representations of animate agents. The movements of the agent can then be anticipated in the short term based solely on physical constraints. In the longer term, taking into account the agent's goals and intentions is useful. Observing goal directed behaviour activates the neural action observation network, and predicting future goal directed behaviour is helped by the observer's own action generating mechanisms. Intentions are critically important in determining actions when interacting with other agents, as several intentions can lie behind an action. Here, interpretation is helped by prior beliefs about the agent and the brain's mentalising system is engaged. Biologically-constrained computational models of action recognition exist, but equivalent models for understanding intentional agents remain to be developed., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recent advances in the neuropsychopharmacology of metacognition indicate a constituent role of glutamate for the integrity of metamnestic processes. However, the extent to which previous results can be generalized across functional domains to characterize the relationship between glutamate and metacognition remains unclear. Here, in a randomized, double-blind, placebo-controlled, preregistered fMRI study, we tested the effects of a psychotomimetic dose (target plasma concentration 100 ng/mL) of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine on metacognition in a perceptual decision-making framework. We collected trial-by-trial metacognitive reports as participants performed a two-alternative forced-choice perceptual task during functional magnetic resonance imaging (fMRI). Results indicated ketamine-induced deterioration in metacognitive performance, whereas no significant effects were observed for perceptual performance, response times and - unexpectedly - metacognitive bias. Whilst there were no detectable ketamine effects on mean BOLD activation, exploratory psychophysiological interaction (PPI) analysis revealed alterations in functional connectivity during metacognitive confidence ratings under ketamine. Specifically, there was increased task-specific connectivity for ketamine compared to placebo between right anterior dorsolateral prefrontal cortex and left middle temporal, supramarginal and precentral gyrus, as well as between right insula/inferior frontal gyrus and left lingual gyrus, possibly indicating re-representations of object-level features supplied for metacognitive evaluations. Overall, these findings contribute towards the emerging picture of the substructures underlying metacognitive operations at the neurotransmitter level and may shed light on a neural pattern characteristic of pharmacologically challenged metacognition., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Loneliness is a public health concern with detrimental effects on physical and mental well-being. Given phenotypical overlaps between loneliness and social anxiety (SA), cognitive-behavioral interventions targeting SA might be adopted to reduce loneliness. However, whether SA and loneliness share the same underlying neurocognitive mechanisms is still an elusive question. The current study aimed at investigating to what extent known behavioral and neural correlates of social avoidance in SA are evident in loneliness. We used a prestratified approach involving 42 (21 females) participants with high loneliness (HL) and 40 (20 females) participants with low loneliness (LL) scores. During fMRI, participants completed a social gambling task to measure the subjective value of engaging in social situations and responses to social feedback. Univariate and multivariate analyses of behavioral and neural data replicated known task effects. However, although HL participants showed increased SA, loneliness was associated with a response pattern clearly distinct from SA. Specifically, contrary to expectations based on SA differences, Bayesian analyses revealed moderate evidence for equal subjective values of engaging in social situations and comparable amygdala responses to social decision-making and striatal responses to positive social feedback in both groups. Moreover, while explorative analyses revealed reduced pleasantness ratings, increased striatal activity, and decreased striatal-hippocampal connectivity in response to negative computer feedback in HL participants, these effects were diminished for negative social feedback. Our findings suggest that, unlike SA, loneliness is not associated with withdrawal from social interactions. Thus, established interventions for SA should be adjusted when targeting loneliness. SIGNIFICANCE STATEMENT Loneliness can cause serious health problems. Adapting well-established cognitive-behavioral therapies targeting social anxiety might be promising to reduce chronic loneliness given a close link between both constructs. However, a better understanding of behavioral and neurobiological factors associated with loneliness is needed to identify which specific mechanisms of social anxiety are shared by lonely individuals. We found that lonely individuals show a consistently distinct pattern of behavioral and neural responsiveness to social decision-making and social feedback compared with previous findings for social anxiety. Our results indicate that loneliness is associated with a biased emotional reactivity to negative events rather than social avoidance. Our findings thus emphasize the distinctiveness of loneliness from social anxiety and the need for adjusted psychotherapeutic protocols., (Copyright © 2022 the authors.)

Methods: Recent randomized control trials (RCTs) have confirmed that antibiotics in acute uncomplicated diverticulitis (AUD) neither accelerate recovery nor prevent complications or recurrences. A retrospective cohort study was conducted, including all consecutive AUD patients hospitalized 2015- 2018 at Helsingborg Hospital (HH) and Skåne University Hospital (SUS), Sweden. HH had implemented a non-antibiotic treatment protocol in 2014 while SUS had not. Main outcomes were proportion of patients treated with antibiotics, complications, recurrences, and adherence to routinely colon evaluation., Results: A total of 583 AUD patients were enrolled, 388 at SUS and 195 at HH. The diagnosis was CT-verified in 320 (83%) vs. 186 (95%) patients respectively (p < 0.001). Forty-three (11%) and 94 (48%) of patients respectively did not receive antibiotics during hospitalization (p < 0.001). CRP was higher in the antibiotic group compared to the non-antibiotic group, both at admission and peak (90 mg/L vs 65 mg/L; p = 0.016) and (138 mg/L and 97 mg/L; p < 0.001). There were no significant differences in recurrences (22.0% vs. 22.6%; p = 0.87) and complications (2.5% vs. 2.9%; p = 0.77) between the antibiotic/non-antibiotic groups., Conclusion: The structured treatment protocol led to reduced antibiotic use and a higher standard of care in terms of CT-verification. Clinicians' compliance to the treatment protocol and best clinical practice was poor and warrants further studies., (© 2022. The Author(s).)

Competing Interests: Declaration of interests We declare no competing interests.

Social cognition and metacognition are frequently impaired in schizophrenia, and these impairments complicate recovery. Recent work suggests that different aspects of metacognition may not be impaired to the same degree. Furthermore, metacognition and the cognitive capacity being monitored need not be similarly impaired. Here, we assessed performance in detecting cues of intentional behaviour as well as metacognition about detecting those cues in schizophrenia. Thirty patients and controls categorized animations of moving dots into those displaying a dyadic interaction demonstrating a chase or no chase and indicated their confidence in these judgments. Perception and metacognition were assessed using signal detection theoretic measures, which were analysed using frequentist and Bayesian statistics. Patients showed a deficit compared to controls in detecting intentionality cues, but showed preserved metacognitive performance into this task. Our study reveals a selective deficit in the perception of intentionality cues, but preserved metacognitive insight into the validity of this perception. It thus appears that impairment of metacognition in schizophrenia varies across cognitive domains - metacognition should not be considered a monolithic stone that is either impaired or unimpaired., Competing Interests: The authors have declared that there are no conflicts of interest in relation to the subject of this study., (© 2021 The Authors.)

Burgeoning evidence indicates that women are more sensitive to the context of an offer and show a stronger propensity to adjust their behavior with changing fairness frames. We evaluated whether the sex hormone estradiol and associated stereotypical beliefs contribute to fairness framings by administering topical estradiol (2 mg) to 108 healthy women and 104 heathy men in a randomized, double-blind, placebo-controlled between-subject study design. Participants played the role of the responder in a modified version of the Ultimatum Game (UG), in which identical offers for the division of a given amount of money were framed as either fair or unfair. Furthermore, participants completed an unframed UG and a delayed discounting task to probe possible effects of estradiol on altruistic preferences and delay gratification. Our results show that women were more sensitive to fairness frames than men. Intriguingly, however, estradiol had sex-specific effects on fairness sensitivity by increasing the acceptance rate of proposals with a fair frame in men and reducing it in women. Furthermore, the mere belief of receiving estradiol treatment significantly increased the acceptance of unfair-framed offers in both sexes, but estradiol did not significantly alter the response to unframed offers and impulsive decision-making. Collectively, our findings indicate that estradiol has opposing effects on the sensitivity to the perceived fairness of economic offers in women and men. The profound effects of estradiol treatment and stereotypical beliefs provide support for the notion that sex differences in fairness framing are rooted in both biological and environmental factors., (Copyright © 2021. Published by Elsevier B.V.)

Study Design: Case report and literature review., Objective: We present a case of a pathologic unstable fracture of the odontoid process due to vertebral osseous sarcoidosis. The surgical management of this unreported pathology is described and a review of the literature is given., Summary of Background Data: Sarcoidosis is a chronic inflammatory systemic disease of unknown etiology, characterized by multiorgan noncaseating granulomatous infiltrations. It affects primarily the lungs, lymphatic system, eyes, skin, heart, and nervous system. Osseous sarcoidosis is usually clinically asymptomatic and therefore frequently under-diagnosed. When it does affect the skull or vertebral column, specific surgical therapy is only necessary in cases with nonmanageable pain or where structural integrity is threatened., Methods: Our patient underwent a so-called semiconservative approach, consisting of a minimally invasive transoral-transpharyngeal approach, surgical debridement of the lytic bony lesion, transplantation of cancellous homologous bone, and carbon chest halo-immobilization. Halo-immobilization was left for 8 weeks, followed by a further 6 weeks with a hard cervical collar., Results: Routine computed tomography scans 3 days, 6, 12, 18 weeks, and 1 year after surgery showed good filling of the original defect with cancellous bone, correct alignment of the upper cervical spine, and progressive fracture consolidation and stability. Surgical site infection (SSI) was not observed. The patient had no neurological postoperative deficits. After initial dysphagia, swallowing was not permanently impaired., Conclusion: Sarcoidosis-induced odontoid fractures can be managed successfully using a semiconservative approach, consisting of transoral-transmucosal, minimally invasive surgical procedure for debridement of the lesion and transplantation of cancellous bone with additional halo-immobilization. Permanent fusion of C1-2 with loss of the cervical range of motion is avoided. Despite performing bone surgery in a potentially markedly contaminated site, bacterial infection was not an issue, possibly supported by the temporary discontinuation of immunosuppressive agents and the prudent use of antibiotics.Level of Evidence: 4., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The timing of surgical resection of synchronous liver metastases from colorectal cancer has been debated for decades. Several strategies have been proposed, but high-level evidence remains scarce. Simultaneous resection of the primary tumour and liver metastases has been described in numerous retrospective audits and meta-analyses. The potential benefits of simultaneous resections are the eradication of the tumour burden in one procedure, overall shorter procedure time, reduced hospital stay with the likely benefits on quality of life and an expected reduction in the use of health care services compared to staged procedures. However, concerns about accumulating complications and oncological outcomes remain and the optimal selection criteria for whom simultaneous resections are beneficial remains undetermined. Based on the current level of evidence, simultaneous resection should be restricted to patients with a limited liver tumour burden. More high-level evidence studies are needed to evaluate the quality of life, complication burden, oncological outcomes, as well as overall health care implications for simultaneous resections.

Only little research has been conducted on the pharmacological underpinnings of metacognition. Here, we tested the modulatory effects of a single intravenous dose (100 ng/ml) of the N -methyl-D-aspartate-glutamate-receptor antagonist ketamine, a compound known to induce altered states of consciousness, on metacognition and its neural correlates. Fifty-three young, healthy adults completed two study phases of an episodic memory task involving both encoding and retrieval in a double-blind, placebo-controlled fMRI study. Trial-by-trial confidence ratings were collected during retrieval. Effects on the subjective state of consciousness were assessed using the 5D-ASC questionnaire. Confirming that the drug elicited a psychedelic state, there were effects of ketamine on all 5D-ASC scales. Acute ketamine administration during retrieval had deleterious effects on metacognitive sensitivity (meta-d') and led to larger metacognitive bias, with retrieval performance (d') and reaction times remaining unaffected. However, there was no ketamine effect on metacognitive efficiency (meta-d'/d'). Measures of the BOLD signal revealed that ketamine compared to placebo elicited higher activation of posterior cortical brain areas, including superior and inferior parietal lobe, calcarine gyrus, and lingual gyrus, albeit not specific to metacognitive confidence ratings. Ketamine administered during encoding did not significantly affect performance or brain activation. Overall, our findings suggest that ketamine impacts metacognition, leading to significantly larger metacognitive bias and deterioration of metacognitive sensitivity as well as unspecific activation increases in posterior hot zone areas of the neural correlates of consciousness., (© The Author(s) 2021. Published by Oxford University Press.)

Importance: Perforated colonic diverticulitis usually requires surgical resection, with significant morbidity. Short-term results from randomized clinical trials have indicated that laparoscopic lavage is a feasible alternative to resection. However, it appears that no long-term results are available., Objective: To compare long-term (5-year) outcomes of laparoscopic peritoneal lavage and primary resection as treatments of perforated purulent diverticulitis., Design, Setting, and Participants: This international multicenter randomized clinical trial was conducted in 21 hospitals in Sweden and Norway, which enrolled patients between February 2010 and June 2014. Long-term follow-up was conducted between March 2018 and November 2019. Patients with symptoms of left-sided acute perforated diverticulitis, indicating urgent surgical need and computed tomography-verified free air, were eligible. Those available for trial intervention (Hinchey stages

Purpose: Adjuvant chemotherapy for colon cancer with lymph node involvement (Stage III) has been the standard of care since the 1990s. Meanwhile, considerable evolvement of surgery combined with dedicated histopathological examinations may have led to stage migration. Furthermore, prognostic factors other than lymph node involvement have proven to affect overall survival. Thus, adjuvant chemotherapy in Stage III colon cancer should be reconsidered. The objective was to compare recurrence rates and survival in stage III colon cancer patients treated with or without adjuvant chemotherapy. Further, to assess the impact of extensive mesenterectomy, lymph node stage and vascular invasion on outcome., Methods: Consecutive patients operated for Stage III colon carcinoma between 31 December 2005 and 31 December 2015 were identified in the pathological code register by matching colon (T67) and either adenocarcinoma (M81403) or mucinous adenocarcinoma (M84803), with lymph node (T08) and metastasis of adenocarcinoma (M81406 or M84806). Medical records of all identified patients were reviewed., Results: Of 216 identified patients, 69 received no postoperative adjuvant chemotherapy (group NC), 69 insufficient adjuvant chemotherapy (FLV or < minimum recommended 6 cycles FLOX, group IC), and 78 sufficient adjuvant chemotherapy (≥ 6 cycles FLOX, group SC). When adjusted for age and comorbidity, 5-year overall survival did not differ statistically significant between groups (76% vs. 83% vs. 85%, respectively). Vascular invasion and a high lymph node ratio significantly reduced overall survival., Conclusion: The findings imply that subgroups of Stage III colon cancer patients have good prognosis also without adjuvant chemotherapy. For definite conclusions about necessity of adjuvant chemotherapy, prospective trials are needed.

Increasing rates of obesity have fueled interest in the factors underlying food choice. While epidemiological studies report that disadvantaged social groups exhibit a higher incidence of obesity, causal evidence for an effect of social contexts on food choice remains scarce. To further our knowledge, we experimentally investigated the effect of disadvantageous social context on food choice in healthy, non-dieting participants. We used three established experimental methods to generate social contexts of different valence in controlled laboratory settings: (i) receiving varying amounts of money in a Dictator Game (DG; n = 40), (ii) being included or excluded in a Cyberball Game (CBG; n = 35), and (iii) performing well, average, or poorly in a response time ranking task (RTR; n = 81). Following exposure to a particular social context, participants made pairwise choices between food items that involved a conflict between perceived taste and health attributes. In line with previous research, stronger dispositional self-control (assessed via a questionnaire) was associated with healthier food choices. As expected, being treated unfairly in the DG, being excluded in the CBG, and performing poorly in the RTR led to negative emotions. However, we did not find an effect of the induced social context on food choice in any of the experiments, even when taking into account individual differences in participants' responses to the social context. Our results suggest that-at least in controlled laboratory environments-the influence of disadvantageous social contexts on food choice is limited., (Copyright © 2020 Rramani, Gerhardt, Grote, Zhao, Schultz and Weber.)

Background: The role of Cytokeratin fraction 21-1 (CYFRA 21-1) as a tumour marker for head and neck cancer is still a matter of research. The aim of the present study was to evaluate the clinical impact of CYFRA 21-1 for patients with oropharyngeal squamous cell carcinoma (OSCC)., Patients and Methods: Data of 180 patients with an initial diagnosis of OSCC of any stage between 2003 and 2017 were retrospectively analysed regarding the association between pretherapeutic CYFRA 21-1 levels, clinical characteristics, overall and disease-free survival. Additionally, the potential of CYFRA 21-1 for the detection of recurrent disease in the follow-up was evaluated. The cut-off value was set at 3.3 ng/ml. The median follow-up time was 2.85 years., Results: A significant correlation of the CYFRA 21-1 concentration at the time of diagnosis and the N-stage was detected (p = 0.01). Patients with CYFRA 21-1 levels > 3.3 ng/ml at first diagnosis showed a significantly shorter overall survival. In the case of disease-progression, a significant increase of CYFRA 21-1 value was found compared to post-therapeutic CYFRA 21-1 levels (9.1 ng/ml versus 5.1 ng/ml; p < 0.01). CYFRA 21-1 level after treatment showed only a low sensitivity of 32% and a specificity of 78% for tumour recurrence., Conclusion: CYFRA 21-1 correlates with the tumour stage and, therefore, the survival of OSCC patients. Posttreatment CYFRA21-1 seems not to be a suitable predictor of tumour recurrence in the further course of the disease. However, a sudden increase of CYFRA 21-1 during follow-up may indicate a tumour recurrence in the individual patient.

Benzodiazepines (BZDs) represent the gold standard of anxiolytic pharmacotherapy; however, their clinical benefit is limited by side effects and addictive potential. Consequently, there is an urgent need to develop novel and safe anxiolytics. The peptide hormone oxytocin (OXT) exhibits anxiolytic-like properties in animals and humans, but whether OXT and BZDs share similar effects on the neural circuitry of fear is unclear. Therefore, the rationale of this ultra-high-field functional MRI (fMRI) study was to test OXT against the clinical comparator lorazepam (LZP) with regard to their neuromodulatory effects on local and network responses to fear-related stimuli. One hundred twenty-eight healthy male participants volunteered in this randomized double-blind, placebo-controlled, between-group study. Before scanning using an emotional face-matching paradigm, participants were randomly administered a single dose of OXT (24 IU), LZP (1 mg), or placebo. On the behavioral level, LZP, but not OXT, caused mild sedation, as evidenced by a 19% increase in reaction times. On the neural level, both OXT and LZP inhibited responses to fearful faces vs. neutral faces within the centromedial amygdala (cmA). In contrast, they had different effects on intra-amygdalar connectivity; OXT strengthened the coupling between the cmA and basolateral amygdala, whereas LZP increased the interplay between the cmA and superficial amygdala. Furthermore, OXT, but not LZP, enhanced the coupling between the cmA and the precuneus and dorsomedial prefrontal cortex. These data implicate inhibition of the cmA as a common denominator of anxiolytic action, with only OXT inducing large-scale connectivity changes of potential therapeutic relevance., Competing Interests: The authors declare no competing interest.

Objective: Childhood maltreatment is a major risk factor for psychopathology associated with interpersonal problems in adulthood, but the etiological pathways involved are still unclear. The authors propose that childhood maltreatment confers risk for dysfunctional behavior in social interactions by altering interpersonal distance preference and the processing of social touch., Methods: Ninety-two medication-free adults (64 of them female) with low, medium, and high levels of childhood maltreatment were tested with an interpersonal distance paradigm and subsequently underwent a social touch functional MRI task during which they rated the perceived comfort of slow touch (C-tactile [CT] optimal speed; 5 cm/s) and fast touch (non-CT-optimal speed; 20 cm/s)., Results: Participants with high childhood maltreatment levels preferred a larger interpersonal distance and experienced fast touch as less comforting compared with participants with no or moderate childhood maltreatment experiences. On the neural level, participants with severe childhood maltreatment exhibited exaggerated responses to fast touch in the right somatosensory and posterior insular cortex, which correlated with lower comfort ratings. Severe childhood maltreatment was associated with decreased activation in the right hippocampus in response to slow touch. This response pattern was not moderated or mediated by childhood maltreatment-associated region-specific reductions in gray matter volume., Conclusions: The study findings suggest that higher childhood maltreatment levels are associated with hypersensitivity characterized by a preference for larger interpersonal distance and discomfort of fast touch. These dysregulations were manifested in a sensory cortical hyperreactivity and limbic CT-related hypoactivation. These results may shed light on why individuals with severe childhood maltreatment exhibit an increased susceptibility to interpersonal dysfunctions and psychiatric disorders in adulthood.

Purpose: The clinical significance of cytokeratin fraction 21-1 (CYFRA 21-1) for patients with head and neck cutaneous squamous cell carcinoma (CSCC) is unknown. Thus, the aim of the study was to evaluate the clinical value of CYFRA 21-1 in the context of treatment and follow-up for these patients., Methods: The clinical, histological and laboratory data of a total of 55 patients with the first diagnosis of head and neck cutaneous squamous cell carcinoma (T1-T4, N0-N2b, M0-1) between 2003 and 2017 were retrospectively analyzed. In 25 cases, the primary tumor could be treated successfully without residual or recurrent disease in the further course. The average follow-up period was 2.3 years. In all patients, pretherapeutic determination of CYFRA 21-1 was performed using the ECLIA test kit. The cut-off value was set at 3.3 ng/ml., Results: In 18 patients (32.7%), regional recurrence was found in the course of treatment. Distant metastases could be observed in two patients (3.6%). In these cases, no significant increase of CYFRA 21-1 blood concentration was detected at the time of recurrence/metastasis. At the time of the first diagnosis, the mean value of CYFRA 21-1 blood concentration was 2.4 ng/ml; and in cases of regional recurrence or distant metastases, the initial mean CYFRA 21-1 concentration was 2.0 ng/ml. There was no statistically significant relationship between CYFRA 21-1 blood concentration and analyzed tumor characteristics., Conclusions: According to current knowledge, the tumor marker CYFRA 21-1 is not clinically significant for treatment and follow-up of patients with head and neck CSCC.

Aim: Meta-analyses indicate positive effects of both antipsychotic and cognitive-behavioural interventions in subjects clinically at high risk (CHR) for psychosis in terms of a delay or prevention of psychotic disorders. However, these effects have been limited regarding social functioning and the relative efficacy of both types of interventions remains unclear. Furthermore, neuroprotective substances seem to be a promising alternative agent in psychosis-prevention as they are associated with few and weak side-effects., Methods: In this multi-centre randomized controlled trial (RCT), we investigate the effects of two interventions on transition to psychosis and social functioning: (a) an integrated preventive psychological intervention (IPPI) including stress-/symptom-management and social-cognitive remediation; (b) N-acetyl-l-cysteine (NAC) as a pharmacological intervention with glutamatergic, neuroprotective and anti-inflammatory capabilities., Results: This is a double-blind, placebo-controlled RCT with regard to NAC and a single-blind RCT with regard to IPPI using a 2 × 2-factorial design to investigate the individual and combined preventive effects of both interventions. To this aim, a total of 200 CHR subjects will be randomized stratified by site to one of four conditions: (a) IPPI and NAC; (b) IPPI and Placebo; (c) NAC and psychological stress management; (d) Placebo and psychological stress management. Interventions are delivered over 26 weeks with a follow-up period of 12 months., Conclusion: This paper reports on the rationale and protocol of an indicated prevention trial to detect the most effective and tolerable interventions with regard to transition to psychosis as well as improvements in social functioning, and to evaluate the synergistic effects of these interventions., (© 2019 John Wiley & Sons Australia, Ltd.)

Distinguishing animate from inanimate objects is fundamental for social perception in humans and animals. Visual motion cues indicative of self-propelled object motion are useful for animacy perception: they can be detected over a wide expanse of visual field, at distance and in low visibility conditions, can attract attention and provide clues about object behaviour. However, the neural correlates of animacy perception evoked exclusively by visual motion cues, i.e. not relying on form, background or visual context, are unclear. We aimed to address this question in four psychophysical experiments in humans, two of which performed during neuroimaging. The stimulus was a single dot with constant form that moved on a blank background and evoked controlled degrees of perceived animacy through parametric variations of self-propelled motion cues. BOLD signals reflecting perceived animacy in a graded manner irrespective of eye movements were found in one intraparietal region. Additional whole-brain and region-of-interest analyses revealed no comparable effects in brain regions associated with social processing or other areas. Our study shows that animacy perception evoked solely by visual motion cues, a basic perceptual process in social cognition, engages brain regions not primarily associated with social cognition., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Social interactions have a major impact on well-being. While many individuals actively seek social situations, others avoid them, at great cost to their private and professional life. The neural mechanisms underlying individual differences in social approach or avoidance tendencies are poorly understood. Here we estimated people's subjective value of engaging in a social situation. In each trial, more or less socially anxious participants chose between an interaction with a human partner providing social feedback and a monetary amount. With increasing social anxiety, the subjective value of social engagement decreased; amygdala BOLD response during decision-making and when experiencing social feedback increased; ventral striatum BOLD response to positive social feedback decreased; and connectivity between these regions during decision-making increased. Amygdala response was negatively related to the subjective value of social engagement. These findings suggest a relation between trait social anxiety/social avoidance and activity in a subcortical network during social decision-making., Competing Interests: JS, TW, MG, GC, AF, BW, RH No competing interests declared, (© 2019, Schultz et al.)

Chains of metallic nanoparticles sustain strongly confined surface plasmons with relatively low dielectric losses. To exploit these properties in applications, such as waveguides, the fabrication of long chains of low disorder and a thorough understanding of the plasmon-mode properties, such as dispersion relations, are indispensable. Here, we use a wrinkled template for directed self-assembly to assemble chains of gold nanoparticles. With this up-scalable method, chain lengths from two particles (140 nm) to 20 particles (1500 nm) and beyond can be fabricated. Electron energy-loss spectroscopy supported by boundary element simulations, finite-difference time-domain, and a simplified dipole coupling model reveal the evolution of a band of plasmonic waveguide modes from degenerated single-particle modes in detail. In striking difference from plasmonic rod-like structures, the plasmon band is confined in excitation energy, which allows light manipulations below the diffraction limit. The non-degenerated surface plasmon modes show suppressed radiative losses for efficient energy propagation over a distance of 1500 nm.

Objective: Routine antibiotic treatment of acute uncomplicated diverticulitis (AUD) has been shown ineffective. In this study, the adherence to a new treatment protocol for uncomplicated diverticulitis was evaluated and the incidence of complications in patients treated with and without antibiotics was investigated., Materials and Methods: A retrospective study of in-patients diagnosed with AUD at Helsingborg Hospital, Sweden between 01 January 2013 and 06 January 2015 was performed. Antibiotics were routinely administrated until 01 May 2014. Thereafter, a new antibiotic-free treatment protocol for uncomplicated diverticulitis was introduced. All the patients were followed regarding complications for minimum one year., Results: A total of 50 patients were studied after the new protocol implementation and, 60% (n = 31) of the patients were treated without antibiotics. Specialists initiated antibiotic therapy significantly more often than registrars (p=.03). More patients in the antibiotic group had comorbidities (p=.03), apart from that, no significant differences in baseline characteristics were noted between treatment groups. Patients treated with antibiotics after introduction of the new protocol had significantly higher C-reactive protein than patients managed without antibiotics (median 117 mg/L vs. 70, p=.005). The hospital stay was shorter in the non-antibiotic group (three days vs. two days; p=.008). No significant differences in complications were observed., Conclusions: Protocol compliance was lower than expected, indicating that implementation of new treatment regimens is challenging. This study confirms that complications are rare in AUD treated without antibiotics. However, the selection of the sickest patients to the treatment with antibiotics limits the interpretation of the results.

Faces that move contain rich information about facial form, such as facial features and their configuration, alongside the motion of those features. During social interactions, humans constantly decode and integrate these cues. To fully understand human face perception, it is important to investigate what information dynamic faces convey and how the human visual system extracts and processes information from this visual input. However, partly due to the difficulty of designing well-controlled dynamic face stimuli, many face perception studies still rely on static faces as stimuli. Here, we focus on evidence demonstrating the usefulness of dynamic faces as stimuli, and evaluate different types of dynamic face stimuli to study face perception. Studies based on dynamic face stimuli revealed a high sensitivity of the human visual system to natural facial motion and consistently reported dynamic advantages when static face information is insufficient for the task. These findings support the hypothesis that the human perceptual system integrates sensory cues for robust perception. In the present paper, we review the different types of dynamic face stimuli used in these studies, and assess their usefulness for several research questions. Natural videos of faces are ecological stimuli but provide limited control of facial form and motion. Point-light faces allow for good control of facial motion but are highly unnatural. Image-based morphing is a way to achieve control over facial motion while preserving the natural facial form. Synthetic facial animations allow separation of facial form and motion to study aspects such as identity-from-motion. While synthetic faces are less natural than videos of faces, recent advances in photo-realistic rendering may close this gap and provide naturalistic stimuli with full control over facial motion. We believe that many open questions, such as what dynamic advantages exist beyond emotion and identity recognition and which dynamic aspects drive these advantages, can be addressed adequately with different types of stimuli and will improve our understanding of face perception in more ecological settings.

What cortical mechanisms allow humans to easily discern the expression or identity of a face? Subjects detected changes in expression or identity of a stream of dynamic faces while we measured BOLD responses from topographically and functionally defined areas throughout the visual hierarchy. Responses in dorsal areas increased during the expression task, whereas responses in ventral areas increased during the identity task, consistent with previous studies. Similar to ventral areas, early visual areas showed increased activity during the identity task. If visual responses are weighted by perceptual mechanisms according to their magnitude, these increased responses would lead to improved attentional selection of the task-appropriate facial aspect. Alternatively, increased responses could be a signature of a sensitivity enhancement mechanism that improves representations of the attended facial aspect. Consistent with the latter sensitivity enhancement mechanism, attending to expression led to enhanced decoding of exemplars of expression both in early visual and dorsal areas relative to attending identity. Similarly, decoding identity exemplars when attending to identity was improved in dorsal and ventral areas. We conclude that attending to expression or identity of dynamic faces is associated with increased selectivity in representations consistent with sensitivity enhancement., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Current perspectives propose that observer models accounting for both optimal and suboptimal behaviour may yield real progress in understanding perception. We propose that such models could, in addition, be very useful for precisely characterising the variation in perception across healthy participants and those affected by psychiatric disorders, as well as the effects of neuromodulators such as oxytocin.

Background: Current neuroimaging perspectives on a variety of mental disorders emphasize dysfunction of the amygdala. The neuropeptide oxytocin (OXT), a key mediator in the regulation of social cognition and behavior, accumulates in cerebrospinal fluid after intranasal administration in macaques and humans and modulates amygdala reactivity in both species. However, the translation of neuromodulatory OXT effects to novel treatment approaches is hampered by the absence of studies defining the most effective dose and dose-response latency for targeting the amygdala., Methods: To address this highly relevant issue, a total of 116 healthy men underwent functional magnetic resonance imaging using a randomized, double-blind, placebo-controlled crossover study design. The experimental rationale was to systematically vary dose-test latencies (15-40, 45-70, and 75-100 minutes) and doses of OXT (12, 24, and 48 international units) in order to identify the most robust effects on amygdala reactivity. During functional magnetic resonance imaging, subjects completed an emotional face recognition task including stimuli with varying intensities ranging from low (highly ambiguous) to high (less ambiguous)., Results: Our results indicate that the OXT-induced inhibition of amygdala responses to fear was most effective in a time window between 45 and 70 minutes after administration of a dose of 24 international units. Furthermore, the observed effect was most evident in subjects scoring high on measures of autistic-like traits. Behavioral response patterns suggest that OXT specifically reduced an emotional bias in the perception of ambiguous faces., Conclusions: These findings provide initial evidence of the most effective dose and dose-test interval for future experimental or therapeutic regimens aimed at targeting amygdala functioning using intranasal OXT administration., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Interessenkonflikt: Kein Interessenkonflikt angegeben..

Background: The validation of potential molecular targets in head and neck squamous cell carcinoma (SCC) is mandatory. β-Catenin and E-cadherin are crucial for cancer progression through epithelial-mesenchymal transition. We analyzed the effect of the tyrosine kinase inhibitors nilotinib, dasatinib, erlotinib and gefitinib on β-catenin and E-cadherin expression in SCC with respect to human papillomavirus (HPV) status., Materials and Methods: Expression of β-catenin and E-cadherin in cell lines UMSCC 11A, UMSCC 14C and CERV196 under the influence of tyrosine kinase inhibitors were analyzed by enzyme-linked immunosorbent assay., Results: All agents reduced β-catenin and E-cadherin expression of HPV16-negative cells. Increased E-cadherin expression was observed after treatment with gefitinib and dasatinib in HPV16-positive cells., Conclusion: All substances, nilotinib, dasatinib, erlotinib and gefitinib have a significant impact on β-catenin and E-cadherin expression in both HPV16-positive and HPV16-negative cells in vitro. Alterations of β-catenin and E-cadherin could provide novel insights for future targeted therapies of head and neck SCC., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The identification of molecular targets in the therapy of human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is a primary aim of cancer research. Matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor receptor (VEGFR) have important roles in the development of HNSCC. The tyrosine kinase inhibitors, nilotinib, dasatinib, erlotinib and gefitinib are well established in the targeted therapy of tumors other than HNSCC. The present study aimed to investigate the alteration of MMP-9 and VEGFR-1 expression patterns following treatment with these tyrosine kinase inhibitors in p16-positive and -negative squamous carcinoma cells. MMP-9 and VEGFR-1 expression was evaluated using an ELISA in HNSCC 11A, HNSCC 14C and p16-positive CERV196 tumor cell lines, following treatment with nilotinib, dasatinib, erlotinib and gefitinib. A statistically significant reduction in MMP-9 and VEGFR-1 expression was observed in the p16-negative HNSCC 11A cells following treatment with all inhibitors (P<0.05). VEGFR-1 expression was significantly increased in p16-positive SCC cells following treatment with nilotinib, dasatinib, erlotinib and gefitinib (P<0.05). The expression of MMP-9 and VEGFR-1 was significantly altered by treatment with nilotinib, dasatinib, erlotinib and gefitinib in vitro . The results of the present study are attributed to the efficacy of the tested drugs and present potential compensatory strategies of cancer cells to avoid the antiangiogenic properties of the tested tyrosine kinase inhibitors in vitro .

Animal studies suggest that N-methyl-D-aspartate receptor (NMDAR) dependent signalling in limbic and prefrontal regions is critically involved in both cognitive and emotional functions. In humans, ketamine-induced transient, and disorder associated chronic NMDAR hypofunction (i.e. in schizophrenia) has been associated with deficient performance in the domains of memory and higher-order emotional functioning, as well as altered neural activity in the underlying limbic-prefrontal circuits. To model the effects of NMDAR hypofunction on the integration of emotion and cognition the present pharmacological fMRI study applied the NMDAR antagonist ketamine (target plasma level=100ng/ml) to 21 healthy volunteers in a within-subject placebo-controlled crossover design during encoding of neutral, positive and negative pictures. Our results show that irrespective of emotion, ketamine suppressed parahippocampal and medial prefrontal activity. In contrast, ketamine selectively increased amygdala and orbitofrontal activity during successful encoding of negative stimuli. On the network level ketamine generally increased medial prefrontal-parahippocampal coupling while specifically decreasing amygdala-orbitofrontal interplay during encoding of negative stimuli. On the behavioural level, ketamine produced generally decreased memory performance and abolished the emotional enhancement of memory after a wash-out period of 5 days. The present findings suggest that ketamine produces general as well as valence-specific effects during emotional memory formation. The pattern partly overlaps with alterations previously observed in patients with schizophrenia., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To compare the outcomes of laparoscopic lavage and sigmoid resection in perforated diverticulitis with purulent peritonitis., Background: Peritonitis secondary to perforated diverticulitis has conventionally been managed by resection and stoma formation. Case series have suggested that patients can be safely managed with laparoscopic lavage, resulting in reduced mortality and stoma formation. Recently, 3 randomized controlled trials have published contradictory conclusions., Methods: MEDLINE from 1946 to present, Cochrane Database of Systematic Reviews, and Cochrane database of Registered clinical trials and EMBASE (all via OVID) were searched using the terms "laparoscopy" AND ("primary resection" OR "Hartmann procedure", OR "sigmoidectomy"), AND "Diverticulitis", AND "Peritonitis" AND "therapeutic irrigation" or "lavage" AND randomized controlled trial and any derivatives of those terms. We included all randomized controlled trials. Data were extracted from each study using a purpose-designed template. Statistical analysis was undertaken using Revman 5., Results: Three randomized controlled trials were identified from 48 potential studies. The analysis included 307 patients of whom 159 underwent laparoscopic lavage. Overall, the rate of reintervention within 30 days postoperatively was 45/159 (28.3%) in the lavage group and 13/148 (8.8%) in the resection group (relative risk 3.01, 95% confidence interval 1.15-7.90). There was no significant difference in Intensive Care Unit admissions, 30 and 90-day mortality, or stoma rates at 12 months., Conclusion: Laparoscopic lavage used in the management of Hinchey grade III diverticulitis leads to more reinterventions within 30 days postoperatively, but does not increase the 30 or 90-day mortality rates compared with sigmoid resection.

The phylogenetically ancient neuropeptide oxytocin has been linked to a plethora of social behaviors. Here, we argue that the action of oxytocin is not restricted to the downstream level of emotional responses, but substantially alters higher representations of attitudes and values by exerting a distant modulatory influence on cortical areas and their reciprocal interplay with subcortical regions and hormonal systems.

Current perspectives on attractiveness-related prosocial biases emphasize the contribution of evolutionarily shaped mating drives. Here, we extend these concepts by highlighting the pivotal role of the hypothalamic peptide oxytocin in augmenting the salience and rewarding value of social stimuli, including the partner's face, thereby fostering social bonding in general and the stability of monogamous pair bonds and offspring care in particular.