Oxytocin-Augmented Modular-Based Group Intervention for Loneliness: A Proof-Of-Concept Randomized Controlled Trial.

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.

Chemotherapy reduces long-term quality of life in recurrence-free colon cancer survivors (LaTE study)-a nationwide inverse probability of treatment-weighted registry-based cohort study and survey.

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.

Behavioral and Neural Dissociation of Social Anxiety and Loneliness.

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.

Laparoscopic lavage for Hinchey III perforated diverticulitis: factors for treatment failure in two randomized clinical trials.

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.

Common and dissociable effects of oxytocin and lorazepam on the neurocircuitry of fear.

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.

Management of acute uncomplicated diverticulitis without antibiotics: compliance and outcomes -a retrospective cohort study.

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.

Clinical relevance of CYFRA 21-1 as a tumour marker in patients with oropharyngeal squamous cell carcinoma.

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.

Direct Observation of Plasmon Band Formation and Delocalization in Quasi-Infinite Nanoparticle Chains.

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.

Perceiving animacy purely from visual motion cues involves intraparietal sulcus.

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.

Acute uncomplicated diverticulitis managed without antibiotics - difficult to introduce a new treatment protocol but few complications.

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.

CYFRA 21-1: a suitable tumor marker in patients with head and neck cutaneous squamous cell carcinoma?

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.

Task-dependent enhancement of facial expression and identity representations in human cortex.

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.

Characterising variations in perceptual decision making.

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.

General and emotion-specific neural effects of ketamine during emotional memory formation.

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.

Laparoscopic Lavage in the Management of Hinchey Grade III Diverticulitis: A Systematic Review.

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.

Oxytocin shapes the priorities and neural representations of attitudes and values.

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.

Oxytocin drives prosocial biases in favor of attractive people.

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.