Development of antibody levels and subsequent decline in individuals with vaccine induced and hybrid immunity to SARS-CoV-2.

OBJECTIVES: This study aimed to compare antibody trajectories among individuals with SARS-CoV-2 hybrid and vaccine-induced immunity. METHODS: Danish adults receiving three doses of BTN162b2 or mRNA-1237 were included prior to first vaccination (Day0). SARS-CoV-2 anti-spike IgG levels were assessed before each vaccine dose, at Day90, Day180, 28 days after 3rd vaccination (Day251), Day365, and prior to 4th vaccination (Day535). SARS-CoV-2 PCR results were extracted from the national microbiology database. Mixed-effect multivariable linear regression investigated the impact of hybrid-immunity (stratified into 4 groups: no hybrid immunity, PCR+ prior to 3rd dose, PCR+ after 3rd dose and before Day365, PCR+ after Day365) on anti-spike IgG trajectories. RESULTS: 4,936 individuals were included, 47% developed hybrid-immunity. Anti-spike IgG increases were observed in all groups at Day251, with the highest levels in those PCR+ prior to 3rd dose (Geometric Mean; 535,647AU/mL vs. 374,665AU/mL with no hybrid-immunity, p=<0.0001). Further increases were observed in participants who developed hybrid immunity after their 3rd dose. Anti-spike IgG levels declined from Day 251-535 in individuals without hybrid-immunity and in those who developed hybrid-immunity prior to their 3rd dose, with lower rate of decline in those with hybrid-immunity. CONCLUSION: Hybrid-immunity results in higher and more durable antibody trajectories in vaccinated individuals.

Longitudinal evaluation of SARS-CoV-2 T cell immunity over 2 years following vaccination and infection.

BACKGROUND: Within a year of the SARS-CoV-2 pandemic, vaccines inducing a robust humoral and cellular immune response were implemented worldwide. However, emergence of novel variants and waning vaccine induced immunity led to implementation of additional vaccine boosters. METHODS: This prospective study evaluated the temporal profile of cellular and serological responses in a cohort of 639 SARS-CoV-2 vaccinated participants, of whom a large proportion experienced a SARS-CoV-2 infection. All participants were infection naïve at the time of their first vaccine dose. Proportions of SARS-CoV-2 Spike-specific T cells were determined after each vaccine dose using the Activation Induced Markers (AIM) assay, while levels of circulating SARS-CoV-2 antibodies were determined by the Meso Scale serology assay. RESULTS: We found a significant increase in SARS-CoV-2 Spike-specific CD4+ and CD8+ T cell responses following the third dose of a SARS-CoV-2 mRNA vaccine as well as enhanced CD8+ T cell responses after the fourth dose. Further, increased age was associated with a poorer response. Finally, we observed that SARS-CoV-2 infection boosts both the cellular and humoral immune response, relative to vaccine-induced immunity alone. CONCLUSION: Our findings highlight the boosting effect on T cell immunity of repeated vaccine administration. The combination of multiple vaccine doses and SARS-CoV-2 infections maintains population T cell immunity although with reduced levels in the elderly.

Impact of COVID-19 pandemic on characteristics, extent and trends in child maltreatment in 34 Euro-CAN COST Action countries: a scoping review protocol.

INTRODUCTION: While the factors commonly associated with an increased risk of child maltreatment (CM) were found to be increased during COVID-19, reports of actual maltreatment showed varying trends. Similarly, evidence regarding the impact of COVID-19 on CM within the European Cooperation on Science and Technology and Network Collaborative (COST) Action countries remains inconsistent. This scoping review aims to explore the extent and nature of evidence pertaining to CM within the countries affiliated with the Child Abuse and Neglect in Europe Action Network (Euro-CAN), funded by the COST. METHODS AND ANALYSIS: Key electronic databases were searched to identify eligible papers, reports and other material published between January 2020 and April 2023: PubMed, EMBASE, PsycINFO, Social Policy and Practice, Scopus and Web of Science. To cover the breadth of evidence, a systematic and broad search strategy was applied using a combination of keywords and controlled vocabulary for four concepts: children, maltreatment, COVID-19 and Euro-CAN countries, without restrictions on study design or language. Grey literature was searched in OpenGrey and Google Scholar. Two reviewers will independently screen full-text publications for eligibility and undertake data extraction, using a customised grid. The screening criteria and data charting will be piloted by the research team.The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) extension for scoping reviews will be followed to present the results. Results will be summarised in a tabular form and narratively. ETHICS AND DISSEMINATION: This review will identify and summarise publicly available data, without requiring ethical approval. The findings will be disseminated to the Euro-CAN Network and reported to the COST Association. They will also be published in a peer-reviewed journal. This protocol is registered on Open Science Framework.

Influence of various factors on the legal outcome of cases of child abuse-experiences gathered at an interdisciplinary forensic examination center in Vienna, Austria.

BACKGROUND AND OBJECTIVE: To improve the currently low conviction rate in cases of child abuse a forensic examination center for children and adolescents (FOKUS) was established in Vienna, Austria. Besides a state of the art treatment combined with forensic documentation, one of FOKUS' key goals is to identify potential areas for improvements within the process legal proceedings in cases of child abuse through constant scientific monitoring. The accompanying study at hand includes all patients referred to FOKUS within a two year timeframe (n = 233), monitoring their progression from first contact with the medical professionals from FOKUS to the end of criminal proceedings. A detailed analysis of case files was performed in those cases that were reported to the legal authorities by the clinicians of FOKUS (n = 87). Aim of the study is to investigate which factors contribute to the initiation of legal proceedings and a successful conviction. RESULTS: Multivariate logistic regression analyses showed that main proceedings were opened more often in cases where the offender was an adult (p < 0.001) or admitted his guilt (p < 0.001) and if digital traces were available (p = 0.001) or trial support (p = 0.024) present. Furthermore, the combined occurrence of medical documentation and victim disclosure was related to a higher probability of opening main trials. CONCLUSION: These findings underline how challenging the successful persecution of an offender in cases of child abuse is.

Cohort analysis of child abuse and neglect cases treated during the initial 2 years of a programme to support hospital-based child protection work in Austria.

OBJECTIVE: To describe characteristics of suspected child abuse and neglect (CAN) cases associated with the decision of paediatric departments (PDs) in Vienna, Austria, to involve services of a regional tertiary child protection service programme (Forensische Kinder- und JugendUntersuchungsStelle, FOKUS). DESIGN: Retrospective cohort analysis of a regional data collection of CAN cases over the first 2 years of FOKUS's operational period (1 July 2015-30 June 2017). SETTING: All CAN cases reported to the PDs of six public hospitals in Vienna. Five of these public hospitals were secondary heath care centres and one was a tertiary healthcare centre. RESULTS: Overall, 231 cases (59.1%) were treated without and 160 (40.9%) with additional involvement of the FOKUS service programme. The odds of a case to be treated without FOKUS involvement were higher if neglect was suspected (OR 3.233, 95% CI 2.024 to 5.279). In contrast, when sexual abuse was suspected, the odds for involvement with FOKUS were significantly higher (OR 7.577, 95% CI 4.580 to 12.879). The odds of being managed with FOKUS services nearly doubled when multiple forms of abuse were suspected (OR 1.926, 95% CI 1.136 to 3.285). The odds for additional FOKUS involvement were significantly lower for patients treated as inpatients (OR 0.239, 95% CI 0.151 to 0.373). CAN patients managed with FOKUS involvement were significantly more often reported to law enforcement (LE) (OR 3.234, 95% CI 2.078 to 5.002). Concurrently, suspected sexual abuse cases and cases reported to LE were more frequently treated in the PD of the tertiary centre than in other PDs (χ2 p<0.001). CONCLUSION: CAN case characteristics significantly influenced if PDs involved a tertiary child protection programme. Suspected sexual abuse, if more than one form of CAN was suspected and cases reported to LE required additional specialist expertise. For suspected neglect involvement of tertiary services seemed less important.

Impact of age and comorbidities on SARS-CoV-2 vaccine-induced T cell immunity.

BACKGROUND: Older age and chronic disease are important risk factors for developing severe COVID-19. At population level, vaccine-induced immunity substantially reduces the risk of severe COVID-19 disease and hospitalization. However, the relative impact of humoral and cellular immunity on protection from breakthrough infection and severe disease is not fully understood. METHODS: In a study cohort of 655 primarily older study participants (median of 63 years (IQR: 51-72)), we determined serum levels of Spike IgG antibodies using a Multiantigen Serological Assay and quantified the frequency of SARS-CoV-2 Spike-specific CD4 + and CD8 + T cells using activation induced marker assay. This enabled characterization of suboptimal vaccine-induced cellular immunity. The risk factors of being a cellular hypo responder were assessed using logistic regression. Further follow-up of study participants allowed for an evaluation of the impact of T cell immunity on breakthrough infections. RESULTS: We show reduced serological immunity and frequency of CD4 + Spike-specific T cells in the oldest age group (≥75 years) and higher Charlson Comorbidity Index (CCI) categories. Male sex, age group ≥75 years, and CCI > 0 is associated with an increased likelihood of being a cellular hypo-responder while vaccine type is a significant risk factor. Assessing breakthrough infections, no protective effect of T cell immunity is identified. CONCLUSIONS: SARS-CoV-2 Spike-specific immune responses in both the cellular and serological compartment of the adaptive immune system increase with each vaccine dose and are progressively lower with older age and higher prevalence of comorbidities. The findings contribute to the understanding of the vaccine response in individuals with increased risk of severe COVID-19 disease and hospitalization.

Vaccination has proven very effective in protecting against severe disease and hospitalization of people with COVID-19, the disease caused by SARS-CoV-2. It is still unclear, however, how the different components of the immune system respond to SARS-CoV-2 vaccination and protect from infection and severe disease. Two of the most predominant components of the immune system are specialized proteins and cells. The proteins circulate in the blood and help clear the virus by binding to it, while the cells either kill the virus or help other cells to produce more antibodies. Here, we examined the response of these two components to the SARS-CoV-2 vaccine in 655 Danish citizens. The response of both components was lower in people over 75 years old and with other diseases. These findings help in understanding the immune responses following SARS-CoV-2 vaccination in people at increased risk of severe symptoms of COVID-19.

Inflammation and Wasting of Skeletal Muscles in Kras-p53-Mutant Mice with Intraepithelial Neoplasia and Pancreatic Cancer-When Does Cachexia Start?

Skeletal muscle wasting critically impairs the survival and quality of life in patients with pancreatic ductal adenocarcinoma (PDAC). To identify the local factors initiating muscle wasting, we studied inflammation, fiber cross-sectional area (CSA), composition, amino acid metabolism and capillarization, as well as the integrity of neuromuscular junctions (NMJ, pre-/postsynaptic co-staining) and mitochondria (electron microscopy) in the hindlimb muscle of LSL-KrasG12D/+; LSL-TrP53R172H/+; Pdx1-Cre mice with intraepithelial-neoplasia (PanIN) 1-3 and PDAC, compared to wild-type mice (WT). Significant decreases in fiber CSA occurred with PDAC but not with PanIN 1-3, compared to WT: These were found in the gastrocnemius (type 2x: −20.0%) and soleus (type 2a: −21.0%, type 1: −14.2%) muscle with accentuation in the male soleus (type 2a: −24.8%, type 1: −17.4%) and female gastrocnemius muscle (−29.6%). Significantly higher densities of endomysial CD68+ and cyclooxygenase-2+ (COX2+) cells were detected in mice with PDAC, compared to WT mice. Surprisingly, CD68+ and COX2+ cell densities were also higher in mice with PanIN 1-3 in both muscles. Significant positive correlations existed between muscular and hepatic CD68+ or COX2+ cell densities. Moreover, in the gastrocnemius muscle, suppressor-of-cytokine-3 (SOCS3) expressions was upregulated >2.7-fold with PanIN 1A-3 and PDAC. The intracellular pools of proteinogenic amino acids and glutathione significantly increased with PanIN 1A-3 compared to WT. Capillarization, NMJ, and mitochondrial ultrastructure remained unchanged with PanIN or PDAC. In conclusion, the onset of fiber atrophy coincides with the manifestation of PDAC and high-grade local (and hepatic) inflammatory infiltration without compromised microcirculation, innervation or mitochondria. Surprisingly, muscular and hepatic inflammation, SOCS3 upregulation and (proteolytic) increases in free amino acids and glutathione were already detectable in mice with precancerous PanINs. Studies of initial local triggers and defense mechanisms regarding cachexia are warranted for targeted anti-inflammatory prevention.

Seroconversion after anti-SARS-CoV-2 mRNA vaccinations among moderate-to-severe psoriatic patients receiving systemic biologicals-Prospective observational cohort study.

It is unclear whether biological antipsoriatic therapies affect seroconversion after messenger ribonucleic acid (mRNA)-based antisevere acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) vaccinations. To assess antibody formation and the incidence of side effects after anti-SARS-CoV-2 mRNA vaccinations in psoriatic patients receiving different biologicals compared to healthy controls. 102 moderate-to-severe psoriatic patients (56.2 [±13.5] years) and 55 age-matched healthy (56.4 ± 13.6 years) volunteers were included in our study. Ten to 21 days after the administration of the second dosage of BNT162b2 or mRNA-1273 vaccine, antibody levels specific to the SARS-CoV-2 spike (S) protein receptor binding domain were monitored. The incidence of postvaccination side effects was recorded and compared to real-life data in the literature. Of the 102 patients, 57 (55.88%) received tumor necrosis factor (TNF), 28 (27.45%) received interleukin (IL)-12/23, 16 (15.68%) received IL-17, and 1 (0.99%) received IL-23 inhibitors. No significant differences in the median serum level of anti-SARS-CoV-2S antibody were observed between the study population and the control group (median IQR range: 1681.0 U/mL (600.0-4844.0) versus 1984.0 U/mL (1000.0-3136.0; p = 0.82). The most frequent side effects of the mRNA vaccines within 7 days after the administration of both dosages were arm pain on the side of injection (23.53% and 23.53%), fatigue (9.80% and 13.72%), headache (4.9% and 5.88%), and chills or shivering (4.9% and 8.82%). Detectable antibodies against SARS-CoV-2S protein appear 10-21 days after the administration of the second dosage of BNT162b2 or mRNA-1273 vaccines in moderate-to-severe psoriatic patients receiving biologicals, similar to those of healthy controls.

Does position of the wrist during cast immobilisation in patients with distal radius fractures affect outcome?

PURPOSE: The position of the wrist during cast immobilisation following closed reduction of distal radius fractures is disputed. A systematic review was initiated to assess if there was any relation between wrist position in the cast and outcome in adult patients with non-operatively treated distal radius fractures. METHODS: A comprehensive search was performed in the bibliographic databases Medline, Embase and Wiley/Cochrane Library from inception up to 27 November 2020. Eligible studies were: randomised controlled trials, prospective and retrospective comparative cohort studies, analysing different positions of the wrist in cast-immobilisation following closed reduction. Primary outcome of the study was functional outcome measured by range of motion. Secondary outcomes were functional outcomes measured by grip strength, patient-reported outcome, radiological outcome and complications such as secondary dislocation and pain. RESULTS: The initial search yielded 2733 studies. Five trials, with 519 patients, were included in this systematic review. Range of motion and radiological outcome was significantly better in patients who were immobilised in dorsiflexion compared to palmar flexion or neutral position, although no clinical important difference was found. There were no significant differences in patient-reported outcome, pain, grip strength or complications. Due to heterogeneity of the included studies, data were unsuitable for a meta-analysis. CONCLUSION: This systematic review showed statistically significant better results in favour of cast immobilisation in dorsiflexion, although this small difference does not seem to be relevant in patients daily activities. SYSTEMATIC REVIEW REGISTRATION NUMBER: Systematic review registration number: PROSPERO 2018 CRD42018085546.

Impact of Interleukin-17 Inhibitor Therapy on Arterial Intima-media Thickness among Severe Psoriatic Patients.

BACKGROUND: Psoriasis is frequently accompanied by cardiovascular diseases based on the shared immunopathogenic pathway. Authors determined the effect of interleukin (IL)-17 inhibitor therapy on arterial intima-media thickness (IMT) among severe psoriatic patients. METHODS: Thirty-one severe psoriatic patients were enrolled. Twenty received secukinumab and 11 received ixekizumab. Before treatment initiation and after 6 months, the carotid-brachial-femoral IMT, the Psoriasis Area Severity Index (PASI), the Dermatology Life Quality of Index (DLQI) and the EuroQol Visual Analogue Scale (EQ VAS) were evaluated. RESULTS: After 6 months, significant ameliorations were observed in PASI (p < 0.001) from 18 to 0, in DLQI (p < 0.001) from 17 to 0, in EQ VAS (p < 0.001) from 60 to 90, in right carotid IMT (p < 0.001) from 1.1 mm to 0.8 mm, in left carotid IMT (p < 0.001) from 1.1 mm to 0.7 mm, in right brachial IMT (p < 0.001) from 0.75 mm to 0.6 mm, in left brachial IMT (p < 0.001) from 0.8 mm to 0.5 mm, in right femoral IMT (p < 0.001) from 0.9 mm to 0.7 mm and in left femoral IMT (p < 0.001) from 0.8 mm to 0.7 mm. CONCLUSIONS: By reducing the inflammation of the vascular wall, anti-IL-17 therapy may have a beneficial long-term effect on cardiovascular complications of systemic inflammation.

Anti-Interleukin-17 Therapy of Severe Psoriatic Patients Results in an Improvement of Serum Lipid and Inflammatory Parameters' Levels, but Has No Effect on Body Composition Parameters.

BACKGROUND: Psoriasis is frequently accompanied by metabolic syndrome. Effect of anti-tumor necrosis factor therapies on increases in body weight is well-known. Data on the effects of interleukin-17 inhibitors are limited. Authors determined the effect of anti-interleukin-17 therapies on the body composition and serum lipid and inflammatory parameters among severe psoriatic patients. METHODS: Thirty-five severe psoriatic patients were enrolled. Twenty-two received secukinumab and 13 received ixekizumab as their 2nd-or 3rd-line biological treatment. Before treatment initiation and 6 months later, laboratory examinations measuring metabolic and inflammatory panels and body composition analyses were performed. RESULTS: After 6 months, a significant reduction was observed in psoriasis area severity index (p < 0.001) from 18 to 0, in c-reactive protein (p < 0.001) from 6.6 to 4.00 mg/L, in low-density lipoprotein-cholesterol (p = 0.004) from 3.69 to 3.19 mmol/L, and an improvement in high-density lipoprotein-cholesterol (p = 0.022) from 1.31 to 1.40 mmol/L. Median baseline body mass index was 32.80 kg/m2. The body composition parameters did not show any significant changes. CONCLUSIONS: Anti-interleukin-17 therapy of severe psoriatic patients does not cause significant changes in body composition parameters. Improvements in the lipid and inflammatory parameters might have a beneficial effect on patients' cardiometabolic status. This effect might be detectable in high-risk obese psoriatic patients.

Does an unconditioned stimulus memory devaluation procedure decrease disgust memories and conditioned disgust? Results of two laboratory studies.

Research has demonstrated that disgust can be installed through classical conditioning by pairing neutral conditioned stimuli (CSs) with disgusting unconditioned stimuli (USs). Disgust has been argued to play an important role in maintaining fear-related disorders. This maintaining role may be explained by conditioned disgust being less sensitive to extinction (i.e., experiencing the CS in the absence of the US). Promising alternatives to extinction training are procedures that focus on the devaluation of US memory representations. In the current study, we investigated whether such devaluation procedures can be successful to counter conditioned disgust. We conducted two laboratory studies (N = 120 and N = 51) in which disgust was conditioned using audio-visual USs. Memory representations of the USs were devalued by having participants recall these USs while they performed a taxing eye-movement task or executed one of several control tasks. The results showed successful conditioned disgust acquisition. However, no strong evidence was obtained that an US memory devaluation procedure modulates disgust memory and diminishes conditioned disgust as indicated by subjective, behavioral, or psychophysiological measures. We discuss the relevance of our results for methodological improvements regarding US memory devaluation procedures and disgust conditioning.

Novel anti-inflammatory therapies to reduce cardiovascular burden of psoriasis.

Psoriasis mainly affects the skin and joints and has serious impacts on the physical, emotional, and financial life of patients. Recent studies have demonstrated that other comorbidities are frequently detected in psoriatic patients. A strong association with the development of cardiovascular diseases, such as hypertension, myocardial infarction, and stroke is responsible for the shortened (by 4.5-5 years) life expectancy of severe psoriatic patients. Systemic inflammation plays an important role in the interrelationship between psoriasis and atherosclerotic plaque formation, which is a common immunopathogenic pathway that explains the multiorgan involvement in psoriasis. As far life-threatening cardiovascular diseases are very often symptom-free, the treating dermatologist's responsibility is to initiate interdisciplinary holistic patient care, which may lead to directly saved patients' lives. Holistic care of severe psoriatic patients should include regular cardiac monitoring using cardiovascular imaging modalities and functional testing to detect even subclinical coronary artery disease. Effective anti-inflammatory treatment with biologic therapies may have beneficial effects on the cardiovascular state and may reduce the incidence of cardiac events. The authors review the latest findings on the shared immunopathogenic background of psoriasis and cardiovascular diseases and discuss the available data about the cardiovascular responses to the currently used biologic treatments.

Job satisfaction of certified employees in viticulture: A qualitative study.

BACKGROUND: The need for qualified employees in wineries leads to a gain in importance of human resource management in the wine industry. Knowledge on job satisfaction of employees in wineries and cooperatives as well as research in human resource management is rare. OBJECTIVE: The aim of this qualitative study is to find aspects affecting job satisfaction of employees in Austrian and German wineries. These identified aspects were analysed with regard to the perceived satisfaction or dissatisfaction of the employees. METHOD: Sixteen qualitative interviews were conducted in Austria and Germany with employed winemakers, production managers and vineyard managers. RESULTS: Aspects of job satisfaction which were found in agricultural studies were validated for employees in wineries. In addition to these influencing factors of job satisfaction, interviewed workers mentioned other important aspects, such as equality issues, development of the company and attachment to the final product, which affect their job satisfaction. CONCLUSIONS: The positive image of the product wine, the wine sector and the profession contributes to a high job satisfaction overall. The personal interest in wine is one of the major factors of job satisfaction. It reduces dissatisfaction with remuneration, monotonous work processes and long working hours. However, employees in wineries saw problems in reconciling family life and work. Furthermore, employees complained about physical strains leading to possible changes in job or position.

Femtosecond Laser-Assisted LASIK in Children With Hyperopia and Anisometropic Amblyopia: 7 Years of Follow-up.

PURPOSE: To analyze clinical and functional results of femtosecond laser-assisted laser in situ keratomileusis (FSLASIK) in children with hyperopia and unilateral anisome-tropic amblyopia. METHODS: The study included 24 patients (24 eyes) aged 5 to 15 years. Before the surgery, the mean manifest refractive spherical equivalent (MRSE) of amblyopic eyes was +3.90 ± 1.60 diopters (D) (range: +1.50 to +6.80 D) and the mean refractive anisometropia was 3.06 ± 1.64 D (range: 0.87 to 7.50 D). Every patient had at least 1 year of ineffective traditional amblyopia treatment before surgery. The mean follow-up period was 7 years (range: 6.9 to 7.4 years). RESULTS: At the final follow-up visit, the mean MRSE of operated eyes was +0.41 ± 1.35 D (range: -1.13 to +3.88 D) (P < .001) and anisometropia in MRSE notation was 1.39 ± 1.15 D (range: 0.00 to 4.63 D). Postoperative spherical equivalent was within ±0.50, ±1.00, and ±2.00 D in 31%, 38%, and 92%, respectively. There were no complications. All patients showed a one to seven line gain of corrected distance visual acuity. CONCLUSIONS: FS-LASIK was an effective method of hyperopia correction in this cohort of children with amblyopia, resulting in reduction in anisometropia, restoration of refractive balance, and functional improvement in the amblyopic eye when traditional methods failed. [J Refract Surg. 2020;36(6):366-373.].

Increased neuronal signatures of targeted memory reactivation during slow-wave up states.

It is assumed that slow oscillatory up-states represent crucial time windows for memory reactivation and consolidation during sleep. We tested this assumption by utilizing closed-loop targeted memory reactivation: Participants were re-exposed to prior learned foreign vocabulary during up- and down-states of slow oscillations. While presenting memory cues during slow oscillatory up-states improved recall performance, down-state cueing did not result in a clear behavioral benefit. Still, no robust behavioral benefit of up- as compared to down-state cueing was observable. At the electrophysiological level however, successful memory reactivation during up-states was associated with a characteristic power increase in the theta and sleep spindle band. No oscillatory changes were observable for down-state cues. Our findings provide experimental support for the assumption that slow oscillatory up-states may represent privileged time windows for memory reactivation, while the interplay of slow oscillations, theta and sleep spindle activity promotes successful memory consolidation during sleep.

Secondary extinction reduces reinstatement of threat expectancy and conditioned skin conductance responses in human fear conditioning.

BACKGROUND AND OBJECTIVES: Secondary extinction refers to the phenomenon that extinction of one conditioned stimulus (CS) results in the reduction of conditioned responses for other CSs conditioned with the same unconditioned stimulus (US). Previous research with rats has demonstrated that secondary extinction can interfere with the return of conditioned fear after a reinstatement manipulation. Here we investigated this phenomenon in two pre-registered studies in humans. METHOD: In both experiments, distinct CSs were paired with an electrical stimulation. Next, conditioned reactions to both CSs were extinguished and thereafter reinstated through the administration of three unsignaled electrical stimulations. Crucially, before participants continued with the reinstatement test, half of the participants received secondary extinction trials whereas the other half did not receive these trials. RESULTS: Our results indicate that secondary extinction reduced reinstatement of threat expectancies and skin conductance responses, but the effect on skin conductance was only found in the second experiment. LIMITATIONS: The studies were conducted in a laboratory setting with healthy students. Additional research will be required to determine the feasibility of applying secondary extinction in a (sub)clinical context. CONCLUSIONS: To our knowledge, this is the first demonstration of secondary extinction and its effect on reinstatement of conditioned fear in humans. We relate our findings to the earlier research with rats and discuss their relevance for exposure therapy.

Contextual correlates of happiness in European adults.

OBJECTIVES: We aimed to examine the associations of both objectively assessed and perceived physical and social neighborhood characteristics with happiness in European adults. In addition, we aimed to study how these associations differed among subgroups. METHODS: Participants (N = 6037) of the cross-sectional SPOTLIGHT survey reported on their level of happiness using a 5-point Likert scale, and on perceived physical and social environmental neighborhood characteristics. Objective physical environmental characteristics were assessed using a Google Street View-based neighborhood audit. Associations of 14 physical and social environmental characteristics with happiness were analyzed using multivariable multinomial regression analyses with clustered standard errors. RESULTS: Living in neighborhoods with higher levels of aesthetics and more water and green space was associated with being very happy. Individuals who perceived their neighborhood to be safer, more functional and more aesthetic were more likely to be very happy. The associations of functionality and aesthetics with happiness were strongest in the Ghent region (Belgium), the Randstad (the Netherlands) and Greater London (United Kingdom). Perceived absence of air pollution was only associated with higher levels of happiness in more highly educated participants. Individuals with a larger social network, more social cohesion and who trusted their neighbors were more likely to be very happy. The association between social networks and happiness was somewhat stronger in men than in women. In general, the associations between environmental characteristics and happiness had similar directions and sizes across socio-economic and socio-demographic subgroups. CONCLUSIONS: This European study provided evidence that both objectively assessed and perceived physical and social characteristics of the neighborhood environment are associated with the happiness of its residents.

Spirometry-Assisted High Resolution Chest Computed Tomography in Children: Is it Worth the Effort?

BACKGROUND: Image quality of high resolution chest computed tomographies (HRCTs) depends on adequate breath holds at end inspiration and end expiration. We hypothesized that implementation of spirometry-assisted breath holds in children undergoing HRCTs would improve image quality over that obtained with voluntary breath holds by decreasing motion artifact and atelectasis. METHODS: This is a retrospective case-control study of HRCTs obtained at a tertiary care children's hospital before and after implementation of a spirometry-assisted CT protocol, in which children ≥8 years of age are first trained in supine slow vital capacity maneuvers and then repeat the maneuvers in the CT scanner, coached by a respiratory therapist. Spirometry-assisted CT scans (cases) were matched by age, gender and diagnosis (cystic fibrosis vs other) to CT scans obtained with voluntary breath holds in the 6 years before implementation of the spirometry assistance protocol (controls), and evaluated by 2 blinded pediatric radiologists. RESULTS: Among both cases and controls (N = 50 each), 10 carried the diagnosis of cystic fibrosis and 40 had other diagnoses. Mean age was 12.9 years (range: 7.5-20.1) among cases and 13.0 (7.1-19.7) among controls. Mean (SD) inspiratory image density among cases was -852 (37) Hounsfield units (HU) and -828 (43) among controls (p = 0.006). Mean (SD) expiratory image density was -629 (95) HU among cases and -688 (83) HU among controls (p = 0.002). Mean (SD) change in image density between inspiratory and expiratory images was +222 (85) HU among cases and +140 (76) HU among controls (p < 0.001). Motion artifact was present on inspiratory images in 5 cases and 9 controls (p = 0.39 by Fisher's exact test), and on expiratory images in 20 cases and 18 controls (p > 0.80). Atelectasis was present on inspiratory images in 8 cases and 9 controls and on expiratory images in 9 cases and 10 controls (p > 0.80). CONCLUSIONS: Spirometry-assisted CTs had a significantly greater difference in lung density between inspiratory and expiratory scans than those performed with voluntary breath holds, likely improving the ability to detect air trapping. No appreciable difference in image quality was detected for the presence of motion artifact or atelectasis.