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Objective We aimed to establish a comprehensive digital phenotype for postpartum hemorrhage (PPH). Current guidelines rely primarily on estimates of blood loss, which can be inaccurate and biased and ignore complementary information readily available in electronic medical records (EMR). Inaccurate and incomplete phenotyping contributes to ongoing challenges in tracking PPH outcomes, developing more accurate risk assessments, and identifying novel interventions. Materials and Methods We constructed a cohort of 71 944 deliveries from the Mount Sinai Health System. Estimates of postpartum blood loss, shifts in hematocrit, administration of uterotonics, surgical interventions, and diagnostic codes were combined to identify PPH, retrospectively. Clinical features were extracted from EMRs and mapped to common data models for maximum interoperability across hospitals. Blinded chart review was done by a physician on a subset of PPH and non-PPH patients and performance was compared to alternate PPH phenotypes. PPH was defined as clinical diagnosis of postpartum hemorrhage documented in the patient’s chart upon chart review. Results We identified 6639 PPH deliveries (9% prevalence) using our phenotype—more than 3 times as many as using blood loss alone (N = 1,747), supporting the need to incorporate other diagnostic and intervention data. Chart review revealed our phenotype had 89% accuracy and an F1-score of 0.92. Alternate phenotypes were less accurate, including a common blood loss-based definition (67%) and a previously published digital phenotype (74%). Conclusion We have developed a scalable, accurate, and valid digital phenotype that may be of significant use for tracking outcomes and ongoing clinical research to deliver better preventative interventions for PPH.

INTRODUCTION: Tumor spread through air spaces (STAS) is associated with locoregional recurrence in patients undergoing limited resection (LR) for non-small cell lung carcinoma (NSCLC). We hypothesized that the observation of STAS in both the initial LR specimen and the additional resection specimen from the same patient, processed using different knives, would provide evidence that STAS is an in vivo phenomenon contributing to locoregional recurrence. METHODS: We retrospectively identified patients with NSCLC (9 adenocarcinoma, 1 squamous cell carcinoma) who underwent LR, had STAS in the LR specimen, and underwent additional resection (lobectomy or LR). The LR and additional resection specimens from each patient were processed at different times using different tissue-processing knives. All specimens were analyzed for STAS. RESULTS: All 10 patients underwent LR with negative margins (R0). All additional resection specimens had STAS: 8 patients had STAS clusters in their completion lobectomy specimens, and 2 had STAS in their additional LR specimens. In 2 patients, STAS was found in the completion lobectomy specimen only after extensive sampling (>10 sections) from the staple line adjacent to the initial LR. CONCLUSION: The presence of STAS in both the LR and the additional resection specimen processed using different knives supports the concept that STAS is an in vivo phenomenon, rather than an artifact from tissue processing. This observation indicates that occult STAS tumor cells can be present in the lung tissue of the remaining unresected lobe after LR and supports the concept that STAS is a contributing factor for locoregional recurrence following LR.

Objective Postpartum hemorrhage (PPH) remains a leading cause of preventable maternal mortality in the United States. We sought to develop a novel risk assessment tool and compare its accuracy to tools used in current practice. Materials and Methods We used a PPH digital phenotype that we developed and validated previously to identify 6639 PPH deliveries from our delivery cohort (N = 70 948). Using a vast array of known and potential risk factors extracted from electronic medical records available prior to delivery, we trained a gradient boosting model in a subset of our cohort. In a held-out test sample, we compared performance of our model with 3 clinical risk-assessment tools and 1 previously published model. Results Our 24-feature model achieved an area under the receiver-operating characteristic curve (AUROC) of 0.71 (95% confidence interval [CI], 0.69-0.72), higher than all other tools (research-based AUROC, 0.67 [95% CI, 0.66-0.69]; clinical AUROCs, 0.55 [95% CI, 0.54-0.56] to 0.61 [95% CI, 0.59-0.62]). Five features were novel, including red blood cell indices and infection markers measured upon admission. Additionally, we identified inflection points for vital signs and labs where risk rose substantially. Most notably, patients with median intrapartum systolic blood pressure above 132 mm Hg had an 11% (95% CI, 8%-13%) median increase in relative risk for PPH. Conclusions We developed a novel approach for predicting PPH and identified clinical feature thresholds that can guide intrapartum monitoring for PPH risk. These results suggest that our model is an excellent candidate for prospective evaluation and could ultimately reduce PPH morbidity and mortality through early detection and prevention.

Physical activity improves quality of life and extends independence in older adults. Yet, how to motivate older adults to engage in physical activity is unclear. In the present study, 4108 older women, aged 70–99, reported how they motivated themselves to move when they did not feel like it, and their hours of physical activity and walking each week. Findings indicated that participants who endorsed more strategies had more hours of physical activity and walking. Strategic categories that correlated with more physical activity include focusing on the benefits and utilizing the surrounding environment to help motivate movement.

Individuals with schizophrenia display substantial deficits in social functioning (SF), characterized by chronic, lifelong presentations. Yet, at present there are few effective interventions to enhance SF in this population. Emerging evidence from studies of clinical populations that display similar SF deficits suggests that aerobic exercise (AE) may improve social skills. However, this putative impact has not been investigated in schizophrenia. Employing a single-blind, randomized clinical trial design, 33 individuals with schizophrenia were randomized to receive 12 weeks of Treatment-As-Usual (TAU; n = 17) or TAU + AE (n = 16) utilizing active-play video games (Xbox 360 Kinect) and traditional AE equipment. Participants completed an evaluation of aerobic fitness (VO2max) as well as self-, informant-, and clinician-reported SF measures at baseline and after 12 weeks. Twenty-six participants completed the study (79%; TAU = 13; AE = 13). At follow-up, the AE participants improved their VO2max by 18.0% versus − 0.5% in the controls (group x time interaction, F1,24 = 12.88; p = .002). Hierarchical stepwise regression analyses indicated improvements in VO2max significantly predicted enhancement in SF as indexed by self-, informant-, and clinician-reported measures, predicting 47%, 33%, and 25% of the variance, respectively (controlling for baseline demographics, medications, mood symptoms, and social networks). Compared to the TAU group, AE participants reported significant improvement in SF (23.0% vs. − 4.2%; group × time interaction, F1,24 = 7.48, p = .012). The results indicate that VO2max enhancement leads to improvements in SF in people with schizophrenia. Furthermore, low VO2max represents a modifiable risk factor of SF in people with schizophrenia, for which AE training offers a safe, non-stigmatizing, and nearly side-effect-free intervention.

Adults are thought to show a sleep-stress spiral in which greater stress worsens sleep quality, which amplifies stress, which leads to worse sleep. This study examined whether adolescents show a similar spiral, and if so, whether coping self-efficacy—believing one can cope with stress—interrupts the spiral. Temporal dynamics of perceived stress, sleep quality, and coping self-efficacy were tracked in 381 9(th) graders (49% female, mean age 14.43, age range 14–16) using daily surveys across two school weeks (3184 observations). Though expected associations were evident between individuals, only a unidirectional path was found within individuals from sleep quality to perceived stress via coping self-efficacy. This challenges the conventional bidirectional understanding of sleep-stress relations and suggests coping self-efficacy as an intervention target.

The lymph node ratio (LNR), which represents the proportion of metastatic lymph nodes resected, has been found to be a prognostic variable in several cancers, but data for Medullary thyroid carcinoma (MTC) are sparse. The aim of this study was to determine the value of the LNR in predicting outcome in patients with MTC.A retrospective multicenter study design of 107 patients with MTC who underwent total thyroidectomy with neck dissection between 1984 and 2016. The association of LNR with patient and tumor characteristics and prognostic factors was evaluated.Study population consisted of 53.3% female, mean age at diagnosis was 50.3 ± 18.4 years; 16.8% had inherited MTC. LNR was positively correlated with tumor size (p = 0.018) and inversely correlated with age at diagnosis (p = 0.024). A higher LNR was associated with extrathyroidal extension (p 0.001), multifocality (p = 0.001), bilateral tumor (p = 0.002), distant metastases (p 0.001), and tumor recurrence (OR = 14.7, p 0.001). LNR was also correlated to postoperative calcitonin levels (p 0.001) and carcinoembryonic antigen (p = 0.011). LNR0.1 was associated with shorter disease-specific survival in patients at risk: tumor larger than 20 mm at diagnosis (p = 0.013), sporadic MTC (p = 0.01), and age above 40 years at diagnosis (p = 0.004). Cox multivariate survival analysis revealed LNR as the only significant independent factor for disease free survival (p = 0.005).This study showed that LNR correlates well with patient and tumor characteristics and prognostic variables. We suggest that LNR should be considered an important parameter for predicting outcome in MTC.

Background An estimated 38% of US adults are obese. Obesity is associated with socioeconomic disparities and increased rates of comorbidities, and is a known risk factor for development of pancreatic cancer. As a fourth leading cause of death in the United States, pancreatic cancer is commonly treated with a pancreatico-duodenectomy (PD), or Whipple procedure. Data regarding the effects of obesity on post-operative complication rate primarily comes from specialized centers, however the results are mixed. Our aim is to elucidate the effects that obesity has on outcomes after PD for pancreatic head cancer using a national prospectively maintained clinical database. Method The 2010–2015 American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) Participant Use Files (PUF) were used as the data source. We identified cases in which PD was performed (CPT code 48150) in the setting of a postoperative diagnosis of pancreatic cancer (ICD9 code 157.0). We excluded cases that had emergency admissions, BMI ≤18.5 kg/m2, intraoperative wound classification of III or IV, and disseminated cancer. Cases with missing BMI, preoperative albumin, operative time, LOS data were also excluded. Multiple imputation for missing sex, race, functional status, and ASA classification using chained equations was performed.16 Patients that had BMI ≥30 kg/m2 were considered obese, and patients with BMI Results 3484 patients underwent pancreaticoduodenectomy for pancreatic cancer. 860 patients were identified as obese. Propensity score analysis was performed matching age, sex, race, functional status, presence of dyspnea, diabetes, hypertension, acute renal failure, dialysis dependence, ascites, steroid use, bleeding disorders, history of chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), weight loss, American Society of Anesthesiologists (ASA) classification, and preoperative albumin levels. After matching, obese patients had higher risk of 30-day postoperative complications compared to control, including organ space wound infections (OR 1.38, 95% CI 1.07–1.79, p = 0.0128), returning to the operating room (OR 1.39, 95% CI 1.01–1.91, p = 0.0461), failure to extubate for greater than 48 h (OR 1.60, 95% CI 1.09–2.34, p = 0.0153), death (OR 1.68, 95% CI 1.01–2.78, p = 0.0453), septic shock (OR 2.22, 95% CI 1.46–3.38, p = 0.0002), pulmonary embolism (OR 2.42, 95% CI 1.07–5.45, p = 0.0332), renal insufficiency (OR 2.67, 95% CI 1.33–5.38, p = 0.0058). Sensitivity analysis yielded similar results with the exception of risk for return to the operating room, death, and pulmonary embolism, P > .05. Conclusion In this large observational study using a national clinical database, obese patients undergoing PD for head of pancreas cancer had increased risk of postoperative complications and mortality in comparison to controls.

When confronted with unwanted negative emotions, individuals use a variety of cognitive strategies for regulating these emotions. The brain mechanisms underlying these emotion regulation strategies have not been fully characterized, and it is not yet clear whether these mechanisms vary as a function of emotion intensity. To address these issues, 30 community participants (17 females, 13 males, Mage = 24.3 years) completed a picture-viewing emotion regulation task with neutral viewing, reacting to negative stimuli, cognitive reappraisal, attentional deployment, and self-distancing conditions. Brain and behavioral data were simultaneously collected in a 3T GE MRI scanner. Findings indicated that prefrontal regions were engaged by all three regulation strategies, but reappraisal showed the least amount of increase in activity as a function of intensity. Overall, these results suggest that there are both brain and behavioral effects of intensity and that intensity is useful for probing strategy-specific effects and the relationships between the strategies. Furthermore, while these three strategies showed significant overlap, there also were specific strategy-intensity interactions, such as frontoparietal control regions being preferentially activated by reappraisal and self-distancing. Conversely, self-referential and attentional regions were preferentially recruited by self-distancing and distraction as intensity increased. Overall, these findings are consistent with the notion that there is a continuum of cognitive emotion regulation along which all three of these strategies lie.

When exposed to others' emotional responses, people often make rapid decisions as to whether these others are members of their group or not. These group categorization decisions have been shown to be extremely important to understanding group behavior. Yet, despite their prevalence and importance, we know very little about the attributes that shape these categorization decisions. To address this issue, we took inspiration from ensemble coding research and developed a task designed to reveal the influence of the mean and variance of group members' emotions on participants' group categorization. In Study 1, we verified that group categorization decreases when the group's mean emotion is different from the participant's own emotional response. In Study 2, we established that people identify a group's mean emotion more accurately when its variance is low rather than high. In Studies 3 and 4, we showed that participants were more likely to self-categorize as members of groups with low emotional variance, even if their own emotions fell outside of the range of group emotions they saw, and that this preference is seen for judgments of both positive and negative group emotions. In Study 5, we showed that this unique preference for low group emotional variance is special to group categorization and does not appear in a more basic face categorization task. Our studies reveal unexplored and important tendencies in group categorization based on group emotions. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Receptor Interacting Protein Kinase 1 (RIPK1) is a key regulator of innate immune signalling pathways. To ensure an optimal inflammatory response, RIPK1 is post-translationally regulated by well characterised ubiquitylation and phosphorylation events, as well as caspase-8 mediated cleavage1–7. The physiological relevance of this cleavage remains unclear, though it is believed to inhibit activation of RIPK3 and necroptosis8. Here we show that heterozygous missense mutations p.D324N, p.D324H and p.D324Y prevent caspase cleavage of RIPK1 in humans and result in early-onset periodic fever episodes and severe intermittent lymphadenopathy, a condition we designate ‘Cleavage-resistant RIPK1-Induced Autoinflammatory’ (CRIA) syndrome. To define the mechanism for this disease we generated a cleavage-resistant Ripk1D325A mutant mouse strain. While Ripk1-/- mice die postnatally from systemic inflammation, Ripk1D325A/D325A mice died during embryogenesis. Embryonic lethality was completely prevented by combined loss of Casp8 and Ripk3 but not by loss of Ripk3 or Mlkl alone. Loss of RIPK1 kinase activity also prevented Ripk1D325A/D325A embryonic lethality, however the mice died before weaning from multi organ inflammation in a RIPK3 dependent manner. Consistently, Ripk1D325A/D325A and Ripk1D325A/+ cells were hypersensitive to RIPK3 dependent TNF-induced apoptosis and necroptosis. Heterozygous Ripk1D325A/+ mice were viable and grossly normal, but were hyper-responsive to inflammatory stimuli in vivo. Our results demonstrate the importance of caspase-mediated RIPK1 cleavage during embryonic development and show that caspase cleavage of RIPK1 not only inhibits necroptosis but maintains inflammatory homeostasis throughout life.

Policy-makers are increasingly turning to behavioural science for insights about how to improve citizens’ decisions and outcomes(1). Typically, different scientists test different intervention ideas in different samples using different outcomes over different time intervals(2). The lack of comparability of such individual investigations limits their potential to inform policy. Here, to address this limitation and accelerate the pace of discovery, we introduce the megastudy–a massive field experiment in which the effects of many different interventions are compared in the same population on the same objectively measured outcome for the same duration. In a megastudy targeting physical exercise among 61,293 members of an American fitness chain, 30 scientists from 15 different US universities worked in small independent teams to design a total of 54 different four-week digital programmes (or interventions) encouraging exercise. We show that 45% of these interventions significantly increased weekly gym visits by 9% to 27%; the top-performing intervention offered microrewards for returning to the gym after a missed workout. Only 8% of interventions induced behaviour change that was significant and measurable after the four-week intervention. Conditioning on the 45% of interventions that increased exercise during the intervention, we detected carry-over effects that were proportionally similar to those measured in previous research(3–6). Forecasts by impartial judges failed to predict which interventions would be most effective, underscoring the value of testing many ideas at once and, therefore, the potential for megastudies to improve the evidentiary value of behavioural science.

We examined whether positive and negative emotion regulation (ER) goals while cognitively reappraising amusing stimuli differentially engage positive (PA) and negative affect (NA) systems. Forty-eight women watched 20-30 s amusing film clips. They were instructed to either respond naturally (no ER goal) or emphasize the film clips' positive (positive ER goal) or negative (negative ER goal) aspects in their interpretation. We measured PA and NA system activity on experiential, expressive, and physiological response channels through self-reported amusement and disgust, electromyography of zygomaticus major and corrugator supercilii, and autonomic nervous system reactivity from respiratory sinus arrhythmia (RSA) and pre-ejection period (PEP). Compared to prefilm baseline activation, natural viewing (no ER goal) of amusing clips increased self-reported amusement (and to a lesser degree disgust), zygomaticus reactivity, and RSA. Compared to no and negative ER goals, reappraising the amusing clips with a positive ER goal decreased corrugator reactivity, decreasing negative emotional expression. Compared to no and positive ER goals, reappraising the amusing clips with a negative ER goal decreased self-reported amusement and zygomaticus reactivity and increased self-reported disgust and corrugator reactivity, decreasing positive and increasing negative emotional experience and expression. We conclude that positive and negative ER goals while reappraising amusing stimuli differentially engaged PA and NA systems: The positive ER goal engaged withdrawal of the expressive NA system, whereas the negative ER goal engaged reciprocal NA-PA system activation on experiential and expressive response channels.

Compared to the general population, individuals with multiple sclerosis (MS) report higher levels of insomnia, depression, fatigue, and paresthesia, and lower levels of emotional competencies (understanding emotions in self and others). Available treatments are limited, and novel approaches to reducing symptoms and enhancing emotional competencies in MS are needed. Two potentially beneficial treatments are Acceptance and Commitment Therapy (ACT) and Mindfulness-Based Stress Reduction (MBSR). The aim of the present study was to investigate the impact of ACT and MBSR on symptoms and emotional competencies in patients with MS.A total of 76 individuals with MS (81.6% females; mean age: 38.88 years; EDSS median: 2; range: 0-5) were randomly assigned to an 8-week ACT treatment, an 8-week MBSR treatment, or a wait-list control condition. At baseline and study-end (week 8), participants completed a series of questionnaires covering symptoms and emotional competencies. At mid-term (week 4), participants rated their insomnia and depression.Over time, symptoms of MS decreased (medium effect size for insomnia, fatigue, and paresthesia, and large effect size for depression) and emotional competencies improved (large effect size), but more so in the MBSR and ACT conditions, compared with the control condition. At study-end, the outcome improvement did not differ between the ACT and MBSR conditions.Both ACT and MBSR led to reduced symptoms and enhanced emotional competencies. Psychotherapeutic interventions such as these should be considered as a means of decreasing symptoms and increasing emotional competencies among individuals with MS.

Social anxiety disorder (SAD) has been shown to be associated with difficulty in the ability to vicariously share others' positive emotions (positive affective empathy). Mixed evidence also suggests potentially impaired recognition of the positive and negative emotions of others (cognitive empathy) and impaired or enhanced sharing of the negative emotions of others (negative affective empathy). Therefore, we examined whether two efficacious treatments for SAD, cognitive-behavioral group therapy (CBGT) and mindfulness-based stress reduction (MBSR), improve empathy in SAD relative to a wait-list condition and whether improvements in empathy mediate improvements in social anxiety. In the context of a randomized controlled trial, participants with SAD completed an empathy task at baseline, posttreatment/wait-list (N = 81), and 1-year follow-up (N = 37). Relative to both MBSR and wait-list, CBGT resulted in significant improvements in positive affective empathy. CBGT-related changes in positive affective empathy also mediated improvements in social anxiety at both posttreatment/wait-list and at 1-year follow-up. Other indices of empathy did not change differentially across the three conditions. Therefore, one way in which CBGT may specifically confer benefits to individuals with SAD is through increasing their ability or willingness to share in the positive emotions of others.

Parents of children diagnosed with autism spectrum disorder (ASD) report higher levels of stress and other negative affective states than parents of typically developing children. One important resource in managing these heightened levels of negative affect is emotion regulation, which in turn depends upon the ability to recognize and understand one's own and others' mental states (referred to as mentalization or reflective functioning). In this study, parents of children with ASD either participated in a mentalization-based group intervention (N = 36) or a delayed treatment (N = 28). Compared to delayed treatment participants, parents in the mentalization-based group had increases in reflective functioning and in the belief that emotions can change. Moreover, they reported decreased behavioral and emotional symptoms in their children, and greater parental self-efficacy. These preliminary findings support previous studies, which have shown that mentalization-based interventions for parents lead to positive outcomes, and suggest that these findings may apply to a diverse population of parents such as those of children with broader autism phenotype or children with different neurological disorders. Further studies to evaluate the effects of the intervention are recommended. Autism Res 2019, 12: 1077-1086. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this study, parents of children with ASD participated in a group intervention designed to increase their awareness of mental states (their own and their children's) and to enhance their emotion regulation. Compared to delayed treatment parents, those in the intervention group showed increased awareness of developmental states, and reported increased belief that emotions can change and decreased levels of behavioral and emotional symptoms in their children.

Background A growing literature supports the contention that closing the divide between dental and medical care can improve access to and coordination of patient care. Health service deficits (HSDs) entail: no routine medical exam, no personal healthcare provider (HCP), no health insurance, and/or delaying medical care because of cost all within the last 12 months. Examining the associations between HSDs and dental care utilization could inform strategies and interventions aimed at narrowing the gap between the medical and dental professions. This study explored whether HSDs are associated with not having a dental care visit within the last 12 months. In addition, the study sought to provide an updated analysis of the characteristics and factors associated with dental care utilization. Methods Two thousand sixteen Behavioral Risk Factor Surveillance System survey data were analyzed using bivariate and multivariable techniques. The outcome variable for this study was: last dental visit was longer than 12 months ago. Results US adults without healthcare insurance, without a personal HCP, who had delayed medical care because of cost, and who had their last routine medical visit longer than 12 months ago had greater odds of not having a dental visit within the last 12 months. Further, this study identified disparities in dental care utilization among males, rural residents, those earning less than $50,000 per year, Non-Hispanic Blacks and Non-Hispanic other races. Individuals with six or more and/or all of their permanent teeth removed and current smokers also had greater odds of not having had a dental care visit in the past 12 months. Conclusions Findings suggest that a stronger integration of medical and dental care might increase dental care utilization. In addition, persistent disparities in dental care utilization remain for several demographic groups. Targeted interventions offer the promise of helping achieve HP 2020 goals for improved oral health.

Emotion regulation (ER) is an important skill for well-being. Cognitive reappraisal is a goal-oriented cognitive change strategy. Acceptance involves decentering from immediate habits of reactivity, observing moment-to-moment shifts in thoughts, emotions, and sensations. These two regulation strategies are thought to have different effects on emotion; however, no study has examined the differential effects of reappraisal and acceptance on behavioral, autonomic, and brain responses in the context of ideographic personally salient negative self-beliefs. Thirty-five right-handed, healthy adults were presented idiographic negative self-beliefs embedded in autobiographical scripts. We measured negative emotion ratings, autonomic psychophysiology, and functional magnetic resonance imaging blood oxygen-level dependent responses while participants read neutral statements, reacted to their own negative self-beliefs, and implemented reappraisal and acceptance strategies. Compared with react, reappraisal resulted in significantly lesser negative emotion and respiration rate; no differences in heart rate and skin conductance level; greater brain responses implicated in cognitive control, language, and social cognition; and lesser amygdala responses. Compared with react, acceptance resulted in significantly lesser negative emotion, respiration rate, and heart rate; no difference in skin conductance level; and greater brain responses in networks implicated in cognitive control and attention. Compared with acceptance, reappraisal resulted in significantly lesser negative emotion; no difference in respiration rate and skin conductance level; higher heart rate; greater brain responses in brain regions implicated in cognitive control; and lesser brain responses in amygdala. Reappraisal is more effective than acceptance in down-regulating negative emotion, but may require greater recruitment of autonomic, cognitive, and brain resources. ClinicalTrials.gov identifier: NCT02036658.

To study the evolution and optimal management of metastatic bone disease (mBD) in patients with neuroendocrine neoplasms (NENs). Seventy-four patients were recruited from four NEN centers in this observational multicenter study. Pancreas and small bowel were the most common primaries (30 and 27%, respectively). Almost all gastrointestinal (GI)-NENs were grades 1 and 2, whereas bronchopulmonary-thymic were atypical carcinoids. Thirty-two (43%) patients had synchronous metastatic bone disease (mBD) and three patients reported bone-specific symptoms; metachronous mBD developed at a median of 35 (range: 4–395) months. Thirty-six (86%) of patients with metachronous mBD had stage IV disease at diagnosis. Somatostatin receptor functional imaging and computed tomography were the modalities mostly used for mBD identification. Fifty-two patients received assessable bone-related therapy (bisphosphonates, denosumab, local radiotherapy, and radionuclide treatment). Improvement in mBD was seen in 5, stable disease in 22, and deterioration in 25 patients. The presence of synchronous mBD and the negative outcome of bone-related therapy negatively affected overall survival (OS). In the multivariate analysis, the stronger predictor of OS was the outcome of bone-related therapy (HR: 4.753; 95% CI: 1.589–14.213). Bisphosphonates therapy was the mostly used bone-specific treatment but its monthly administration did not affect OS. At last follow-up, 39 patients were alive with OS 50 (14–463) months. Early investigation for mBD offers a prognostic marker of patients with NENs, since synchronous mBD has a negative impact on survival. The outcome of bone-related therapy affects OS but the monthly administration of bisphosphonates did not show a benefit over less intense schemes.

Whole-brain resting-state functional MRI (rs-fMRI) during 2 wk of upper-limb casting revealed that disused motor regions became more strongly connected to the cingulo-opercular network (CON), an executive control network that includes regions of the dorsal anterior cingulate cortex (dACC) and insula. Disuse-driven increases in functional connectivity (FC) were specific to the CON and somatomotor networks and did not involve any other networks, such as the salience, frontoparietal, or default mode networks. Censoring and modeling analyses showed that FC increases during casting were mediated by large, spontaneous activity pulses that appeared in the disused motor regions and CON control regions. During limb constraint, disused motor circuits appear to enter a standby mode characterized by spontaneous activity pulses and strengthened connectivity to CON executive control regions.

The aim of the present study was to investigate the effects of milk composition changes on the in vitro growth of bovine mastitis pathogens. Nutritional requirements of three major bovine mastitis pathogens Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Streptococcus uberis (S. uberis) were investigated in vitro. We used ultra-high temperature (UHT) treated milk with different contents of fat, protein, and carbohydrates to test the influence of the availability of various milk constituents on pathogen growth characteristics. Additionally, the bacterial growth was investigated under experimentally modified nutrient availability by dilution and subsequent supplementation with individual nutrients (carbohydrates, different nitrogen sources, minerals, and different types of B vitamins) either to milk or to a conventional medium (thioglycolate broth, TB). Varying contents of fat, protein or lactose did not affect bacterial growth with the exception of growth of S. uberis being promoted in protein-enriched milk. The addition of nutrients to diluted whole milk and TB partly revealed different effects, indicating that there are media-specific growth limiting factors after dilution. Supplementation of minerals to diluted milk did not affect growth rates of all studied bacteria. Bacterial growth in diluted whole milk was decreased by the addition of high concentrations of amino acids in S. aureus, and by urea and additional B vitamins in E. coli and S. aureus. The growth rate of S. uberis was increased by the addition of B vitamins to diluted whole milk. The present results demonstrate that growth-limiting nutrients differ among pathogen types. Because reduced bacterial growth was only shown in diluted milk or TB, it is unlikely that alterations in nutrient availability occurring as a consequence of physiological changes of milk composition in the cow's udder would directly affect the susceptibility or course of bovine mastitis.

Five-year absolute breast cancer risk prediction models are required to comply with national guidelines regarding risk reduction regimens. Models including the Gail model are under-utilized in the general population for various reasons, including difficulty in accurately completing some clinical fields. The purpose of this study was to determine if a streamlined risk model could be designed without substantial loss in performance. Only the clinical risk factors that were easily answered by women will be retained and combined with an objective validated polygenic risk score (PRS) to ultimately improve overall compliance with professional recommendations. We first undertook a review of a series of 2,339 Caucasian, African American and Hispanic women from the USA who underwent clinical testing. We first used deidentified test request forms to identify the clinical risk factors that were best answered by women in a clinical setting and then compared the 5-year risks for the full model and the streamlined model in this clinical series. We used OPERA analysis on previously published case-control data from 11,924 Gail model samples to determine clinical risk factors to include in a streamlined model: first degree family history and age that could then be combined with the PRS. Next, to ensure that the addition of PRS to the streamlined model was indeed beneficial, we compared risk stratification using the Streamlined model with and without PRS for the existing case-control datasets comprising 1,313 cases and 10,611 controls of African-American (n = 7421), Caucasian (n = 1155) and Hispanic (n = 3348) women, using the area under the curve to determine model performance. The improvement in risk discrimination from adding the PRS risk score to the Streamlined model was 52%, 46% and 62% for African-American, Caucasian and Hispanic women, respectively, based on changes in log OPERA. There was no statistically significant difference in mean risk scores between the Gail model plus risk PRS compared to the Streamlined model plus PRS. This study demonstrates that validated PRS can be used to streamline a clinical test for primary care practice without diminishing test performance. Importantly, by eliminating risk factors that women find hard to recall or that require obtaining medical records, this model may facilitate increased clinical adoption of 5-year risk breast cancer risk prediction test in keeping with national standards and guidelines for breast cancer risk reduction.

Childhood maltreatment (CM) is thought to be linked to adult narcissistic traits. However, it remains unclear how CM is associated with each type of narcissism, vulnerable and grandiose, and what mechanism mediates these links. One potential candidate is dissociation. This study examines the relations among CM, dissociation, vulnerable narcissism, and grandiose narcissism. A total of 322 women completed self-reported questionnaires assessing CM, dissociation, vulnerable narcissism, and grandiose narcissism. To examine the relations among CM, dissociation, and each type of narcissism, we performed Pearson’s correlations and mediation analyses. In secondary analyses, we conducted latent class analyses to classify different types of CM and to assess their relations with the study variables. We found small to moderate correlations between CM and vulnerable narcissism, ( r = .35, p < .001) and CM and grandiose narcissism ( r = .2, p < .001), with the former association being greater than the latter ( z = –3.25, p < .001). Dissociation was found to mediate the link between CM and each type of narcissism ( p < .001). Results suggest that CM may play a role in the etiology of vulnerable and grandiose narcissism, and that dissociation links CM to each type of narcissism. Findings highlight that CM may lead to different responses in terms of narcissism—through the same mediation process.

To evaluate the efficacy of topical mupirocin in reducing Staphylococcus aureus colonization in infants in the neonatal intensive care unit (NICU).A prospective double-blind randomized controlled trial of mupirocin vs placebo in S aureus-colonized infants was conducted in a tertiary care NICU between October 2016 and December 2019. Weekly universal active surveillance with polymerase chain reaction screening identified colonized infants. Colonized infants received a 5-day course of mupirocin (mupirocin group) or petroleum jelly (control group). Repeat courses were given for additional positive screens.A total of 216 infants were enrolled; 205 were included in data analyses. Primary decolonization was more successful for mupirocin-treated infants (86 of 104 [83%]) than for controls (20 of 101; 20%) (P .001). Although recurrent S aureus colonization occurred frequently (59 of 81 [73%] mupirocin-treated and 26 of 33 [79%] controls), subsequent decolonization remained more successful for mupirocin-treated infants than for controls (38 of 49 [78%] vs 2 of 21 [10%]; P .001). Subgroup analyses of infants of ≤30 weeks' gestational age yielded similar results; decolonization occurred more often in mupirocin-treated infants compared with control infants (63 of 76 [83%] vs 13 of 74 [18%]; P .001). Bacterial sterile site infections tended to be less frequent in mupirocin-treated infants compared with controls (2 of 104 [2%] vs 8 of 101 [8%]; P = .057). No invasive S aureus infections occurred in mupirocin-treated infants, but 50% of infections in controls were from S aureus, and 1 resulted in death.Universal active surveillance and targeted treatment with topical mupirocin is a successful decolonization strategy for NICU infants and may prevent S aureus infection. However, S aureus colonization frequently recurs, necessitating repeat treatment.Clinicaltrials.gov: NCT02967432.

The purpose of this study was to assess the efficacy and safety of (177)Lu-DOTATATE in patients with somatostatin receptor (SSR)–positive lung neuroendocrine tumors (NETs). Methods: This is a retrospective review of the outcome of patients with typical carcinoid (TC) and atypical carcinoid (AC), treated with (177)Lu-DOTATATE at 2 ENETS Centers of Excellence. Morphologic imaging (RECIST 1.1) and (68)Ga-DOTATATE PET/CT responses were assessed at 3 mo after completion of (177)Lu-DOTATATE. Concordance between 2 response assessment methods was evaluated by κ statistics. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier analysis and compared by Log-rank test. Treatment-related adverse events (AEs) were graded based on Common Terminology Criteria for Adverse Events, version 5. Results: Of 48 patients (median age, 63 y; 13 women), 43 (90%) had AC and 5 (10%) TC. Almost all patients (47, 98%) were treated due to progression. Most patients (40, 83%) received somatostatin analogs, and 10 patients (20%) had prior everolimus, chemotherapy, or both. All patients had high SSR expression (≥ modified Krenning score 3) on pretreatment (68)Ga-DOTATATE PET/CT. Patients received a median 4 (range, 1–4) cycles of (177)Lu-DOTATATE (33% with concurrent radiosensitizing chemotherapy) to a median cumulative activity of 27 GBq (range, 6–43GBq). At a median follow-up of 42 mo, the median PFS and OS were 23 mo (95% CI, 18–28 mo) and 59 mo (95% CI, 50-not reached [NR]), respectively. Of 40 patients with RECIST-measurable disease and 39 patients with available (68)Ga-DOTATATE PET/CT, response categories were partial response, 20% (95% CI, 10%–35%) and 44% (95% CI, 30%–59%); stable disease, 68% (95% CI, 52%–80%) and 44% (95% CI, 30%–59%); and progressive disease, 12% (95% CI, 5%–27%) by both, respectively. There was a moderate concordance between response categories by RECIST and (68)Ga-DOTATATE PET/CT, weighted κ of 0.51 (95% CI, 0.21–0.68). Of patients with stable disease by RECIST, those with partial response on (68)Ga-DOTATATE PET/CT had a longer OS than those with no response, NR versus 52 mo (95% CI, 28–64), hazard ratio 0.2 (95% CI, 0.1–0.6), P

Objective The authors conducted a case series to determine arrest of root surface caries lesions in older adults when teeth were treated topically with 38 % silver diamine fluoride (SDF). Methods The study was a prospective, single center case series. The patients were 62 older adults (age ≥55 years) who sought treatment at a dental school clinic. To be included, a patient needed to have at least one active root caries lesion. Lesions were rinsed and then dried with air, isolated, and then 38 % SDF was applied for two minutes with a microbrush. Treated lesions were re-evaluated at 2–3 weeks. Treatment was repeated every six months. Survival analysis methods for clustered data were used to estimate the caries lesion arrest probability over time separately for root surfaces and at crown margins. Results Fifty-five participants returned for follow-up (44 % female, mean age (SD) 79.8 (7.4)). The probability of a lesion arresting with treatment ranged from 82.9 to 91.6%. Arrest rates at 18 months were slightly higher in root surfaces than around crown margins, 91.6 % (95 % CI 69.1–97.1) versus 89.8 % (95 % CI 71.6–96.3). All furcal lesions (n = 7) were arrested by 6 months, 100 % (95 % CI 59–100). Conclusion and Clinical Significance Repeated application of 38 % SDF at 6-month intervals was effective in arresting decay of root surface lesions and lesions around crowns in older adults. Study outcomes support SDF treatment for older adult patients who are frail and residing in nursing homes or dependent living facilities.

Upper urinary tract urothelial cell carcinoma (UTUC) is a rare entity. The incidence in Germany is approximately 2/100,000 with a ratio between women and men of 1:2.5. Most clinical signs are nonspecific, which is why early diagnosis is rarely successful. Computed tomography urography in combination with diagnostic ureterorenoscopy is currently the gold standard in the diagnostics of UTUC. Regarding surgical treatment, radical nephroureterectomy (RNU) with resection of a bladder cuff remains the method of choice, although the radical approach is developing towards laparoscopic/robotic or endourological procedures with preservation of kidney tissue. Due to the high recurrence rate (22-47%) of urothelial carcinoma inside the bladder, close follow-up after RNU is mandatory.

Purpose Inadequate nutrition is common in individuals diagnosed with cancer. The present study evaluated the association between preoperative albumin and postoperative complications in otherwise healthy patients presenting with newly diagnosed squamous cell carcinoma of the oral cavity primarily managed with ablative surgery. Patients and Methods A retrospective cohort study of patients with newly diagnosed oral squamous cell carcinoma from 2005 to 2019 was performed. Patients referred to and managed by a single surgeon (ERC) and who had not received any nutritional support in the preoperative period were included in the study. The primary predictor variable was preoperative albumin level. Other studied variables were patient demographic data and TNM stage. Complications related to primary ablative surgery represented the primary outcome variable. χ2 analysis was completed to assess for significant associations between independent albumin groups (4+, 3.5 to 3.9, and 3.0 to 3.4 g/dL) in relation to postoperative complications. Multivariate logistic regression analysis was completed to control for clinical variables and medical comorbidities when testing the association between albumin and dehiscence. Results The patient cohort included 268 individuals; of whom, 154 were men. The average age of the patients at surgery was 63 years. When controlling for all other variables, albumin was the only statistically significant predictor of postoperative dehiscence, P = .005. Patients with albumin of 3.5 to 3.9 g/dL had 3.24 times higher odds of dehiscence (95% confidence interval 1.42 to 7.38) in comparison with participants in the 4+ g/dL group. There was no difference of odds between the 3.0 to 3.4 group and the 4+ reference group. Conclusions Our study demonstrated that among those individuals meeting the inclusion criteria, there is a statistically significant association between lower albumin levels and postoperative complication rates, specifically dehiscence.

Background Difficulties in emotion regulation are a key risk factor for affective disorders. The Emotion Regulation Questionnaire (ERQ) is a 10-item measure of two emotion regulation strategies, cognitive reappraisal and expressive suppression. It is widely used tool in the United States, however, most psychometric studies of the ERQ have so far been conducted with college students and some researchers have recently questioned its factorial validity in non-student samples. In this study, we conducted the first confirmatory factor analysis study of the ERQ in a United States general community sample. Method We examined the ERQ's factor structure, measurement invariance across age, education and gender categories, internal consistency reliability, and concurrent validity with a sample of 508 adults. Results The intended two-factor model (cognitive reappraisal, expressive suppression) was an excellent fit to the data, and this structure was invariant across different age, education, and gender categories. Both ERQ scale scores had good omega and alpha reliabilities, and correlated as expected with depression and anxiety symptoms. Cognitive reappraisal was negatively correlated with these symptoms, whereas expressive suppression was positively correlated with these symptoms. Limitations We did not include a clinical sample and future psychometric studies of the ERQ in specialised clinical populations would be useful. Conclusions The ERQ appears to have strong psychometric properties when used with general community members from the United States. ERQ scores can be confidently used and compared across adults of different ages, genders, and educational backgrounds.

One important long-term outcome of childhood maltreatment is thought to be impairments in intimate relationships. However, the specific nature of these impairments is not well understood. To address this gap, we examined the long-term relation of sexual, emotional, and physical abuse/neglect to four key aspects of sexuality in women and men: importance of sex, intimacy in sex, pain during sex, and pleasure during sex. As part of the U.S. longitudinal National Survey of Midlife Development, 807 participants in their mid-life (410 women, 397 men) completed measures of recollected childhood maltreatment and current aspects of adult sexuality. These measures were obtained at baseline (at which time the mean age was 53.28 years (SD = 10.97) and again 10 years later. For women at baseline, emotional abuse was positively associated with pleasure, emotional neglect was negatively associated with intimacy and with pleasure, physical abuse was positively associated with pain, and physical neglect was associated with importance of sex. For men, no significant associations were found. Prospectively, for women, sexual abuse predicted increases in pleasure during sex, and physical abuse significantly predicted increases in pain during sex. For men, physical neglect significantly predicted increases in pain. We discuss these sex differences and the role these results may play in the detrimental long-term effects of childhood maltreatment.

Rectal neuroendocrine neoplasia (NEN) is more common than other NEN origins, but is less commonly metastatic. However, when present, distant disease carries a particularly poor prognosis. Evidence guiding optimal treatment of such patients is lacking. We assessed PRRT outcomes in patients with somatostatin receptor (SSTR) positive metastatic rectal NEN from two referral centres. Patients treated with PRRT were retrospectively reviewed. Morphologic (RECIST 1.1), SSTR imaging responses and toxicity were assessed 3 months post-PRRT. Kaplan-Meier estimate was used to determine progression-free survival (PFS) and overall survival (OS) from start of PRRT. Twenty-seven consecutive patients (M = 20, age 31-81 years) were reviewed. The majority (70%) had ENETs grade 2 disease (19 patients), three had Grade 3, one Grade 1, and four not documented. Overall, 63% (10/16 patients with available FDG PET/CT) had FDG avid disease. Twenty-six patients were treated for disease progression. Most had 177Lu-DOTA-octreotate with median cumulative activity of 30 GBq, median four cycles. 14 patients had radiosensitising chemotherapy (5FU or capecitabine). At 3 months post-PRRT, CT disease control rate (DCR) was 96%: partial response was observed in 70% (19/27) and stable disease in 26%. All but one had partial SSTR imaging response. The median PFS was 29 months. Ten patients died, with median overall survival 81 months with a median follow-up of 67 months. Seventeen patients had further treatments after initial PRRT (10 had further cycles of PRRT). Three patients had grade 3 lymphopenia, without significant renal toxicity, MDS or leukaemia. Our results indicate high efficacy and morphologic responses with minimal toxicity and very encouraging survival from PRRT in patients with metastatic rectal NEN despite the adverse prognostic features of this cohort. Further prospective PRRT trials are warranted in this subgroup.

Individuals' theories about emotions-the beliefs about the nature of emotions and the ability to influence them-have been linked to well-being. However, their causal role is not clear. To address this issue, we delivered a randomized controlled intervention to 1,645 middle school students that targeted their theories of emotion through interactive online modules. Students were taught that they could modify their emotions, get better at modifying their emotions with practice, and use strategies to improve their well-being. One month later, we found that students assigned to the intervention condition (compared to an active control condition) reported more adaptive theories of emotion and greater emotional well-being in school, although well-being outside of school was unchanged. Secondary analyses showed that these effects were present regardless of students' race, gender, or grade level. These findings suggest that theories of emotion may be a promising target for improving adolescent well-being. (PsycINFO Database Record

People's beliefs about emotions may be grouped into two main categories: beliefs about the controllability of emotions and beliefs about the usefulness of emotions. These beliefs influence emotion regulation efforts and mental health, so the assessment of these beliefs is important. However, few psychometric measures are available, particularly for assessing the usefulness dimension. In this study (N = 161), we address this issue by developing and conducting an initial validation of a 16-item self-report measure called the Emotion Beliefs Questionnaire (EBQ). Confirmatory factor analyses found its structure to consist of three first-order factors: a controllability factor spanning both negatively and positively valenced emotions (General-Controllability), and two valence-specific usefulness factors (Negative-Usefulness, Positive-Usefulness). All first-order factors also loaded together on a higher-order factor, representing an overall maladaptive beliefs about emotions construct. All subscale and composite scores had good levels of internal consistency. Correlational and regression analyses found that EBQ scores related in expected ways with other measures, and were significant predictors of emotion regulation abilities and psychopathology. We conclude that the beliefs about emotions construct is multidimensional, and the EBQ appears to be a promising new tool to assess it.

Many of our emotions arise in social contexts, as we interact with and learn about others. What is not yet clear, however, is how such emotions unfold when we either react to others or attempt to regulate our emotions. To address this issue, 30 healthy volunteers reacted to or reappraised positive or negative information that was paired with neutral faces. While they were doing this task, we assessed pupillary responses. We also asked participants to provide ratings of accountability and experienced emotion. Findings indicated that appraised accountability increased in response to emotional information, and changes in accountability were associated with commensurate changes in valence reports and increased pupil diameter. During reappraisal, accountability and emotion decreased, but pupil diameter increased. The findings highlight the importance of accountability appraisals during the generation and regulation of emotional reactions to others, while also documenting pupillary increases during emotional reactivity and regulation.

Middle-aged and older adults constitute a high suicide risk group. Among adults aged 50 years old and older, suicide rates increased and suicide deaths almost doubled during the period from 2000 to 2015. Suicide rates are elevated for patients hospitalized for suicidality (i.e. active suicidal ideation or suicide attempt) and the three months post-hospitalization is the time of the highest suicide risk. Psychosocial interventions for middle-aged and older adults hospitalized for suicidality are sparse. In this article, we present the main aspects, stages, techniques and a clinical case study of Cognitive Reappraisal Intervention for Suicide Prevention (CRISP), a psychosocial intervention targeting cognitive reappraisal to reduce suicide risk in middle-aged and older adults who have been recently hospitalized for suicidal ideation or suicide attempt. CRISP is based on the theory that hospitalization for suicidality is preceded by an emotional crisis (“perfect storm”); this emotional crisis is related to personalized (patient- and situation-specific) triggers; and identifying these personalized triggers and the associated negative emotions and providing strategies for an adaptive response to these triggers and negative emotions will reduce suicidal ideation and improve suicide prevention. CRISP therapists identify these triggers of negative emotions and employ cognitive reappraisal techniques to reduce these negative emotions. The cognitive reappraisal techniques have been selected from different psychosocial interventions and the affective neuroscience literature and have been simplified for use with middle-aged and older adults. CRISP may fill a treatment need for the post-discharge high risk period for middle-aged and older adults hospitalized for suicidality.

We examined (1) differences between controls and patients with social anxiety disorder (SAD) in emotional clarity and attention to emotions; (2) changes in emotional clarity and attention to emotions associated with cognitive-behavioral group therapy (CBGT), mindfulness-based stress reduction (MBSR), or a waitlist (WL) condition; and (3) whether emotional clarity and attention to emotions moderated changes in social anxiety across treatment. Participants were healthy controls (n = 37) and patients with SAD (n = 108) who were assigned to CBGT, MBSR, or WL in a randomized controlled trial. At pretreatment, posttreatment, and 12-month follow-up, patients with SAD completed measures of social anxiety, emotional clarity, and attention to emotions. Controls completed measures at baseline only. At pretreatment, patients with SAD had lower levels of emotional clarity than controls. Emotional clarity increased significantly among patients receiving CBGT, and changes were maintained at 12-month follow-up. Emotional clarity at posttreatment did not differ between CBGT and MBSR or between MBSR and WL. Changes in emotional clarity predicted changes in social anxiety, but emotional clarity did not moderate treatment outcome. Analyses of attention to emotions were not significant. Implications for the role of emotional clarity in the treatment of SAD are discussed.

The widespread use of neck sonography in recent years has led to a dramatic increase in the detection of thyroid cancer, accompanied by changes in the clinicopathologic features of the disease. However, small papillary carcinomas account for the bulk of this increase, while little is known about temporal changes in medullary thyroid carcinoma (MTC). The aim of this study was to evaluate trends in the presentation, treatment, and outcome of MTC.Patients treated for MTC at four medical centers in Israel were divided into three groups by year of diagnosis: 19811995 (period A), 1996-2005 (period B), and 2006-2016 (period C). Clinicopathologic and survival data were collected retrospectively from the medical files and compared between the groups.The cohort included 182 patients (54.9% female) with a mean age of 49.2 ± 18.7 years: 43 (23.6%) diagnosed in period A, 54 (29.7%) in period B, and 85 (46.7%) in period C. No significant differences were found between the groups in primary tumor size (25.7 ± 18.9 mm, 26.6 ± 18 mm, and 23.7 ± 17.6 mm, respectively), proportion of micro-MTC (30.8%, 20.0%, and 25.3%, respectively), or TNM staging. Age at diagnosis significantly increased over time (38.7 ± 17.2 years, 51.7 ± 18.4 years, and 53.7 ± 17.7 years, respectively; p 0.001), and the rate of familial MTC significantly decreased (41.9%, 14.8%, and 8.2%, respectively; p = 0.002). Although the implementation of cervical lymph node dissection increased (62.1%, 78.4%, and 85%, respectively; p = 0.01), detection of metastatic lymph nodes decreased from 88.9% in period A to 65.0% in periods B and C (p = 0.06). There was no difference between the groups in disease-specific survival or disease-free state at one year from diagnosis (37.5%, 43.1%, and 50%, respectively) and last follow-up (27%, 41.2%, and 48%, respectively). Similar findings on MTC presentation and outcomes were obtained when only patients with non-familial MTC were analyzed.Unlike differentiated thyroid cancer, most of the presenting features of MTC have not changed over time. The most significant temporal change is a decreased rate of familial MTC. Despite more extensive surgery and the use of new treatment modalities in recent years, significant improvement in disease-related outcomes were not found.

Background Major depressive disorder (MDD) is characterized by maladaptions in affective brain circuitry and in emotion regulation. It remains unknown whether these maladaptions characterize first-degree relatives of probands who are unaffected yet have a higher risk of developing MDD. Methods Participants were 72 unaffected first-degree relatives of probands with MDD and 66 matched non-relative controls. We investigated brain circuit function and self-reported emotion regulation strategies for reappraisal and suppression. During functional magnetic resonance imaging, we probed circuitry relevant to both negative and positive valence systems using facial expressions signaling potential threat, sadness and happiness, presented under both conscious and subliminal viewing conditions. We compared groups using a statistically controlled region of interest (ROI) approach including the amygdala, insula, anterior cingulate cortex (ACC), ventromedial prefrontal cortex and dorsolateral prefrontal cortex. We also used a data-driven cluster analytic approach for characterizing the relatives by their brain function profiles. Results As a group, relatives were distinguished by hyper-reactivity of the pregenual ACC during subliminal viewing of threat-related expressions but hypo-activation of the amygdala, insula and dorsal ACC during explicit viewing of the same threat-related expressions and sadness. When considered individually, this brain function profile characterized two-thirds of relatives, and these relatives were also less likely to use reappraisal to regulate negative emotion. Limitations The design was cross-sectional and therefore does not provide direct evidence as to the trait- (versus state-) like profile observed in relatives. Conclusions Familial risk for MDD may involve a disruption to the normal recruitment of neural circuits for appraising salient emotions, both implicit and explicit. Interventions targeting reappraisal strategies for regulating negative emotion may serve to buffer this risk.

Liver metastases are common in patients with neuroendocrine tumors (NETs), having a negative impact on disease prognosis. The options for selective therapy in patients with unresectable multiple liver metastases are limited to TACE (transarterial chemoembolization), TAE (transarterial embolization), or SIRT (selective internal radiation therapy). To explore the clinical outcome, survival and safety of these therapies in NETs patients. Retrospective case series of consecutive patients (mean age 56.6 years, 59% male) treated at two tertiary university medical centers from 2005 to 2015. Fifty-seven patients with G1, G2, and low G3 NETs with liver metastases were investigated (pancreatic NET (pNET), 24; small bowel, 16; unknown origin (UKO), 9; rectal, 3; lung, 3; and gastric, 2). Fifty-three patients underwent TACE, three patients underwent TAE, and one patient underwent SIRT. Clinical improvement and tumor response were observed in 54/57 patients (95%), together with marked decreased in tumor markers. The median time to tumor progression following the first treatment was 14 ± 16 months. The median overall survival was 22 ± 18 months, more pronounced in the pNET, followed by small bowel and UKO subgroups. There was a trend for a better survival in patients with disease limited to the liver and in whom the primary tumor was resected. Hepatic intra-arterial therapies are well tolerated in the majority of patients with NETs and liver metastases and associated with both clinical improvement and tumor stabilization for prolonged periods. These therapies should be always considered, irrespective of the presence of extrahepatic metastasis.

IMPORTANCE: Cognitive behavioral group therapy (CBGT) and mindfulness-based stress reduction (MBSR) are thought to help patients with social anxiety disorder (SAD) via distinct emotion-regulation mechanisms. However, no study has compared the effects of CBGT and MBSR on brain and negative emotion indicators of cognitive reappraisal and acceptance in patients with SAD. OBJECTIVE: To investigate the effects of CBGT and MBSR on reappraisal and acceptance in patients with SAD and to test whether treatment-associated brain changes are associated with social anxiety symptoms 1 year posttreatment. DESIGN, SETTING, AND PARTICIPANTS: In this randomized clinical trial, a total of 108 unmedicated adults diagnosed with generalized SAD were randomly assigned to 12 weeks of CBGT, MBSR, or waitlist. The final sample included 31 patients receiving CBGT, 32 patients receiving MBSR, and 32 waitlist patients. Data were collected at the psychology department at Stanford University from September 2012 to December 2014. Data were analyzed from February 2019 to December 2020. INTERVENTIONS: CBGT and MBSR. MAIN OUTCOMES AND MEASURES: Changes in self-reported negative emotion and functional magnetic resonance imaging (fMRI) blood oxygen level–dependent (BOLD) signal within an a priori–defined brain search region mask derived from a meta-analysis of cognitive reappraisal and attention regulation 1 year posttreatment. RESULTS: Of 108 participants, 60 (56%) were female. The mean (SD) age was 32.7 (8.0) years. Self-reported race and ethnicity data were collected to inform the generalizability of the study to the wider population and to satisfy the requirements of the National Institutes of Health. From the categories provided by the National Institutes of Health, 47 participants selected White (43.5%), 42 selected Asian (38.9%) 10 selected Latinx (9.3%), 1 selected Black (1%), 1 selected Native American (1%), and 7 selected more than 1 race (6.5%). CBGT and MBSR were associated with a significant decrease in negative emotion (partial η(2) range, 0.38 to 0.53) with no significant between-group differences when reacting (β, −0.04; SE, 0.09; 95% CI, −0.11 to 0.08; t(92) = −0.37; P = .71), reappraising (β, −0.15; SE, 0.09; 95% CI, −0.32 to 0.03; t(92) = −1.67; P = .10), or accepting (β, −0.05; SE, 0.08; 95% CI, −0.20 to 0.11; t(92) = −0.59; P = .56). There was a significant increase in BOLD percentage signal change in cognitive and attention-regulation regions when reappraising (CBGT = 0.031; MBSR = 0.037) and accepting (CBGT = 0.012; MBSR = 0.077) negative self-beliefs. CBGT and MBSR did not differ in decreased negative emotion and increased reappraisal and acceptance BOLD responses. Reappraisal-associated MBSR (vs CBGT) negative emotions and CBGT (vs MBSR) brain responses were associated with social anxiety symptoms 1 year posttreatment. CONCLUSIONS AND RELEVANCE: The results of this study suggest that CBGT and MBSR may be effective treatments with long-term benefits for patients with SAD that recruit cognitive and attention-regulation brain networks. Despite contrasting models of therapeutic change, CBT and MBSR may both enhance reappraisal and acceptance emotion regulation strategies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036658

Background Asymptomatic carotid artery stenosis (ACS) has a low risk of stroke. To achieve an advantage over noninterventional best medical treatment (BMT), carotid endarterectomy (CEA) or carotid artery stenting (CAS) must be performed with the lowest possible risk of stroke. Therefore, an analysis of risk-elevating factors is essential. Grade of ipsilateral and contralateral stenosis as well as plaque morphology are known risk factors in ACS. Methods The randomized, controlled, multicenter SPACE-2 trial had to be stopped prematurely after recruiting 513 patients. 203 patients were randomized to CEA, 197 to CAS, and 113 to BMT. Within one year, risk factors such as grade of stenosis and plaque morphology were analyzed. Results Grade of contralateral stenosis (GCS) was higher in patients with any stroke (50%ECST vs. 20%ECST; p=0.012). Echolucent plaque morphology was associated with any stroke on the day of intervention (OR 5.23; p=0.041). In the periprocedural period, any stroke was correlated with GCS in the CEA group (70%ECST vs. 20%ECST; p=0.026) and with echolucent plaque morphology in the CAS group (6% vs. 1%; p=0.048). In multivariate analysis, occlusion of the contralateral carotid artery (CCO) was associated with risk of any stroke (OR 7.00; p=0.006), without heterogeneity between CEA and CAS. Conclusion In patients with asymptomatic carotid artery stenosis, GCS, CCO, as well as echolucent plaque morphology were associated with a higher risk of cerebrovascular events. The risk of stroke in the periprocedural period was increased by GCS in CEA and by echolucent plaque in CAS. Due to small sample size, results must be interpreted carefully.

Objective The aim of the current study is to assess the safety and efficacy of external trigeminal nerve stimulation (e-TNS) via a transcutaneous supraorbital stimulator as an acute treatment for migraine attacks. Materials and Methods This was a prospective, open-labeled clinical trial conducted at the Columbia University Headache Center (NY, USA). Thirty patients who were experiencing an acute migraine attack with or without aura were treated with a one-hour session of e-TNS (CEFALY Technology) at the clinic. Pain intensity was scored using a visual analogue scale (VAS) before the treatment, after the one-hour treatment session, and at two hours after treatment initiation. Rescue migraine medication intake was recorded at 2 and 24 hours. Results Thirty patients were included in the intention-to-treat analysis. Mean pain intensity was significantly reduced by 57.1% after the one-hour e-TNS treatment (−3.22 ± 2.40; p

Cognitive-Behavioral Group Therapy (CBGT) and Mindfulness-Based Stress Reduction (MBSR) are efficacious in treating social anxiety disorder (SAD). It is not yet clear, however, whether they share similar trajectories of change and underlying mechanisms in the context of SAD. This randomized controlled study of 108 unmedicated adults with generalized SAD investigated the impact of CBGT vs. MBSR on trajectories of social anxiety, cognitive reappraisal, and mindfulness during 12 weeks of treatment. CBGT and MBSR produced similar trajectories showing decreases in social anxiety and increases in reappraisal (changing the way of thinking) and mindfulness (mindful attitude). Compared to MBSR, CBGT produced greater increases in disputing anxious thoughts/feelings and reappraisal success. Compared to CBGT, MBSR produced greater acceptance of anxiety and acceptance success. Granger Causality analyses revealed that increases in weekly reappraisal and reappraisal success predicted subsequent decreases in weekly social anxiety during CBGT (but not MBSR), and that increases in weekly mindful attitude and disputing anxious thoughts/feelings predicted subsequent decreases in weekly social anxiety during MBSR (but not CBGT). This examination of temporal dynamics identified shared and distinct changes during CBGT and MBSR that both support and challenge current conceptualizations of these clinical interventions. ClinicalTrials.gov identifier NCT02036658.

People's beliefs about their ability to control their emotions predict a range of important psychological outcomes. It is not clear, however, whether these beliefs are playing a causal role, and if so, why this might be. In the current research, we tested whether avoidance-based emotion regulation explains the link between beliefs and psychological outcomes. In Study 1 (N = 112), a perceived lack of control over emotions predicted poorer psychological health outcomes (increased self-reported avoidance, lower well-being, and higher levels of clinical symptoms), and avoidance strategies indirectly explained these links between emotion beliefs and psychological health. In Study 2 (N = 101), we experimentally manipulated participants' emotion beliefs by leading participants to believe that they struggled (low regulatory self-efficacy) or did not struggle (high regulatory self-efficacy) with controlling their emotions. Participants in the low regulatory self-efficacy condition reported increased intentions to engage in avoidance strategies over the next month and were more likely to avoid seeking psychological help. When asked if they would participate in follow-up studies, these participants were also more likely to display avoidance-based emotion regulation. These findings provide initial evidence for the causal role of emotion beliefs in avoidance-based emotion regulation, and document their impact on psychological health-related outcomes.

Background Juvenile Dermatomyositis (JDM) is a pediatric vasculopathy characterized primarily by skin and muscle involvement. Cardiac findings have been reported in children with JDM but have rarely been investigated in detail. Methods We aimed to describe the relevant clinical and laboratory cardiac findings of a cohort of patients with JDM, followed at one centre, at disease diagnosis. Results We performed a retrospective review of 105 patients with JDM, followed from 1991 to 2007. Six of 70 patients (9%, 6% of the entire cohort) had abnormal electrocardiographic (ECG) findings, while 26 of 54 patients (48%, 25% of the entire cohort) had abnormal echocardiographic (echo) findings. Many of these findings were either mild or unlikely to be a result of JDM. Conclusions Our findings suggest that cardiac abnormalities at JDM disease onset are frequently seen, but are rarely significant findings due to disease; however, JDM patients should be considered for screening for cardiac disease as late cardiac complications are well recognized.

There are several special situations in which urinary lithiasis presents management challenges to the urologist. An in-depth knowledge of the pathophysiology, unique anatomy, and treatment options is crucial in order to maintain good health in these patients. In this review, we summarize the current literature on the management of the following scenarios: bladder stones, stones in bowel disease, during pregnancy, in association with renal anomalies, with skeletal deformities, in urinary diversions, and in children.

Homesickness can put individuals at risk for a host of adjustment difficulties. The millions of students that leave home for college each year may be particularly susceptible to experiencing homesickness. There is little work, however, examining individual variation in homesickness over time and how these changes predict different outcomes in college. The present study examines weekly levels of homesickness during the first term of college and tests the associations between homesickness and various aspects of adjustment. Results showed that, on average, homesickness decreased slightly across the first semester of college, but there were individual differences in homesickness trajectories. Freshmen who reported higher levels of homesickness showed worse overall adjustment to college, even when controlling for negative emotional experience and prior adjustment. Homesickness was associated with poorer social outcomes, but these social difficulties were limited to interactions with others in the college environment. Academic outcomes were not adversely impacted by homesickness. Findings suggest that homesickness is a common experience for freshmen, and, despite its relatively transient nature, homesickness has important implications for college adjustment. (PsycINFO Database Record

Social anxiety disorder (SAD) is associated with elevated negative and diminished positive affective experience. However, little is known about the way in which individuals with SAD perceive and respond emotionally to the naturally-unfolding negative and positive emotions of others, that is, cognitive empathy and affective empathy, respectively. In the present study, participants with generalized SAD (n = 32) and demographically-matched healthy controls (HCs; n = 32) completed a behavioral empathy task. Cognitive empathy was indexed by the correlation between targets’ and participants’ continuous ratings of targets’ emotions, whereas affective empathy was indexed by the correlation between targets’ and participants’ continuous self-ratings of emotion. Individuals with SAD differed from HCs only in positive affective empathy: they were less able to vicariously share others’ positive emotions. Mediation analyses revealed that poor emotional clarity and negative interpersonal perceptions among those with SAD might account for this finding. Future research using experimental methodology is needed to examine whether this finding represents an inability or unwillingness to share positive affect.