Larger Tumor Size and Elevated Serum Chromogranin A Levels Predict Metastatic Disease on DOTATATE Imaging in Patients with Gastroenteropancreatic Neuroendocrine Tumors.

PURPOSE: DOTATATE PET/CT (DOTATATE) is superior to conventional imaging in detecting metastasis for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, limited availability, high-cost, and additive radiation exposure necessitate guidelines for its use. This study seeks to investigate the relationship between clinical characteristics and metastasis on DOTATATE. METHODS: This was a retrospective analysis of 815 patients who underwent DOTATATE at UCLA from 2014 to 2022. After applying inclusion and exclusion criteria, the study cohort consisted of 163 patients with pathologically diagnosed GEP-NETs, who either underwent primary tumor resection within 1-year prior, or had not undergone resection at the time of DOTATATE imaging. The presence of metastasis was determined using DOTATATE. Fisher's exact test, chi-squared test, and Mann-Whitney test were conducted to compare intergroup difference. Multivariate analysis was performed to identify clinical characteristics associated with metastasis on DOTATATE. RESULTS: Of patients with GEP-NETs, 40.5% (n = 66) were diagnosed with metastases by using DOTATATE. Those with metastatic disease were more likely to exhibit a larger primary tumor size (median 3.4 vs. 1.2, cm, P < 0.001), elevated serum chromogranin A level (CgA, median 208 vs. 97, mg/ml, P = 0.005), and higher tumor grade (P < 0.001). Primary tumor size ≥2 cm and serum CgA level ≥150 ng/mL for metastatic disease had a sensitivity and specificity of 64% and 89%, and 72% and 59%, respectively. Multivariate analysis demonstrated that primary tumor size (≥2/<2, cm, odds ratio [OR] 47.90, P < 0.001), tumor functionality (functional/nonfunctional, adjusted OR 10.17 P = 0.008), serum CgA level (≥150/<150, ng/ml, OR 6.25, P = 0.005), and tumor grade G2 (G2/G1, OR 9.6, P < 0.001) were independently associated with metastases on DOTATATE. CONCLUSIONS: Among patients with GEP-NETs, primary tumor size ≥2 cm, serum CgA level ≥150 ng/mL, and tumor grade G2 are associated with an increased risk of metastases on DOTATATE, and these predictors may be helpful to identify patients where DOTATATE is indicated for complete staging.

'I thought we would be nourished here': The complexity of nutrition/food and its relationship to mental health among Arab immigrants/refugees in Canada: The CAN-HEAL study.

Nutritional psychiatry suggests that diet quality impacts one's mental health (MH). The relationship between food/nutrition and MH may be particularly salient for immigrants/refugees who often experience high risk for household food insecurity and MH challenges. An innovative collaborative community-based participatory research and integrated knowledge translation approach was adopted to explore food/nutrition needs as they relate to MH among Arab immigrants/refuges (AIR) in Ontario, Canada. The goal was to co-identify areas that require social change and co-produce applicable knowledge for service improvement. The CAN-HEAL study used a multi-methodological approach, employing qualitative interviews, photovoice and a questionnaire survey. A combination of three sampling approaches (convenience, snowball and purposive) was used to recruit sixty socio-demographically-diverse adult AIR participants. The research was guided by an integrated bio-psycho-socio-cultural framework. Participants reported various socio-economic and structural barriers to nutritious eating. Food quality/safety was a significant concern and source of anxiety among AIR; food mislabeling, the widespread presence of genetically/chemically modified foods and expired/rotten food products were associated with negative MH. Participants experienced an alarming prevalence of food insecurity (65%), which was associated with negative MH. Intersections among age, gender, religion, socio-economic status, parenthood, disability, and place of residence played a considerable role in how nutrition, food security, and dietary intake impacted AIR's MH and caused substantial disparities within the AIR community. The food/nutrition-MH relationship among AIR is multi-faceted, and various psycho-socio-cultural pathways/processes were found to shape MH. Intersectoral collaboration between health and non-health sectors is needed to implement a co-proposed socio-political and community-level action plan to achieve nutrition and health equity for AIR and other similar marginalized groups.

Association between tooth loss-related speech and psychosocial impairment with cognitive function: A pilot study in Hong Kong's older population.

BACKGROUND: Tooth loss has been associated with cognitive decline, but the underlying mechanisms involving speech and psychosocial impairment remain unclear. OBJECTIVES: To investigate the impact of tooth loss-related speech and psychosocial impairment on cognitive function in Hong Kong's older population. METHODS: Seventy-six Cantonese-speaking participants between the ages of 51-92 were classified into three groups: patients with complete dentures (CD), partially edentulous patients with less than 10 occluding tooth pairs (OU <10), and at least 10 occluding tooth pairs (OU ≥10). Cognitive function was assessed using the Montreal Cognitive Assessment Hong Kong Version, One-minute Verbal Fluency Task and Hayling Sentence Completion Test. Objective and subjective speech assessments were carried out using artificial intelligence speech recognition algorithm and a self-designed speech questionnaire. The impact of tooth loss on psychosocial condition was evaluated by the Reading the Mind in the Eyes Test and a self-designed questionnaire. Statistical analyses (one-way ANOVA, ANCOVA, Kruskal-Wallis test, Spearman correlation test) were performed. RESULTS: Tooth loss was significantly associated with lower cognitive function (p = .008), speech accuracy (p = .018) and verbal fluency (p = .001). Correlations were found between cognitive function and speech accuracy (p < .0001). No significant difference in tooth loss-related psychosocial impact was found between the three groups. CONCLUSION: While warranting larger sample sizes, this pilot study highlights the need for further research on the role of speech in the association between tooth loss and cognitive function. The potential cognitive impact of tooth retention, together with its known biological and proprioceptive benefits, supports the preservation of the natural dentition.

Well-being of undergraduate dental students: Questionnaire design, findings and future directions.

INTRODUCTION: The recent pandemic has highlighted the importance of addressing well-being in the overall health of students. There is a need for support systems within dental schools to help students demonstrate resilience, adapt to learning environments and thrive in their professional careers. OBJECTIVES: The main aim of the study was to evaluate Bachelor of Dental Surgery (BDS) students' understanding and experience of well-being. The objectives were to create a suitable survey to assess students' well-being, investigate the factors affecting dental students' well-being and develop a student well-being action plan based on the analysis of the survey. METHODS: A literature review was conducted to identify and critically assess existing measures of well-being in dental students. Four domains of well-being (emotional, physical, social, intellectual) relevant to dental students were identified. Through a comprehensive iterative process, a two-part survey was developed and tested, which measured individual experiences of well-being across the four domains and collected feedback on proposed initiatives to support student well-being. The survey was disseminated to all 452 dental students from Years 1 through 6, of which 71% (321) responded. RESULTS: The survey revealed low levels of overall well-being among the dental student population, which worsened with increasing years of clinical study. Fear of failing exams presented the biggest challenge with regard to emotional well-being, while sleep deprivation and occupational health hazards most affected the physical well-being domain. Intellectual well-being was compromised by insufficient free time to pursue extracurricular interests and concerns about achieving the required skills. Despite a majority experiencing positive relationships with their peers and tutors, less than a fifth agreed that the Faculty of Dentistry 'supported my well-being as a dental student'. CONCLUSION: As the first investigation of the well-being of dental students in Hong Kong, the key stressors identified were examinations, long schedules and the physical burden of dental work, which are consistent with international literature. The findings reveal students' needs and preferences for well-being initiatives which will be optimized in the implementation of student-centred curricular activities.

Incorporating emotion coaching into behavioral parent training program: evaluation of its effectiveness.

Disruptive behaviors in childhood yield negative mental health outcomes. Both behavioral management and emotion coaching parenting programs were effective in reducing children's disruptive behaviors. This randomized control trial (RCT) study evaluated the effectiveness of a community clinic-based, parent training program that incorporated emotion coaching into behavioral training (BPEC) for 119 parents who expressed difficulty in handling their elementary school-aged children's disruptive behaviors. These parents were randomly assigned to the treatment group or waitlist control. Pre-tests, post-tests, and 3-month delayed post-tests were administered. Compared to those in the waitlist control group, participants in the BPEC group reported significantly (a) fewer child oppositional behaviors and ADHD symptoms and (b) more positive aspects of the parent-child relationship. Significant short-term effects were maintained after 3-month for parent-reported, child oppositional behaviors. Thus, BPEC effectively reduced the disruptive behaviors of children.

Theory-based behavioral change interventions to improve periodontal health.

Periodontal disease is a significant global health burden affecting half of the world's population. Given that plaque and inflammation control are essential to the attainment of periodontal health, recent trends in preventive dentistry have focused on the use of behavioral models to understand patient psychology and promote self-care and treatment compliance. In addition to their uses in classifying, explaining and predicting oral hygiene practices, behavioral models have been adopted in the design of oral hygiene interventions from individual to population levels. Despite the growing focus on behavioral modification in dentistry, the currently available evidence in the field of periodontology is scarce, and interventions have primarily measured changes in patient beliefs or performance in oral hygiene behaviors. Few studies have measured their impact on clinical outcomes, such as plaque levels, gingival bleeding and periodontal pocket reduction, which serve as indicators of the patient's disease status and quality of oral self-care. The present narrative review aims to summarize selected literature on the use of behavioral models to improve periodontal outcomes. A search was performed on existing behavioral models used to guide dental interventions to identify their use in interventions measuring periodontal parameters. The main models were identified and subsequently grouped by their underlying theoretical area of focus: patient beliefs (health belief model and cognitive behavioral principles); stages of readiness to change (precaution adoption process model and transtheoretical model); planning behavioral change (health action process approach model, theory of planned behavior and client self-care commitment model); and self-monitoring (self-regulation theory). Key constructs of each model and the findings of associated interventions were described. The COM-B model, a newer behavioral change system that has been increasingly used to guide interventions and policy changes, is discussed with reference to its use in oral health settings. Within the limitations of the available evidence, interventions addressing patient beliefs, motivation, intention and self-regulation could lead to improved outcomes in periodontal health. Direct comparisons between interventions could not be made due to differences in protocol design, research populations and follow-up periods. The conclusions of this review assist clinicians with implementing psychological interventions for oral hygiene promotion and highlight the need for additional studies on the clinical effects of behavioral model-based interventions.

Physical activity as a modifiable risk factor for periodontal disease.

Non-communicable diseases (NCDs), which contribute significantly to global morbidity, are largely preventable through behavioral changes. As with other NCDs, periodontitis is associated with modifiable risk factors such as smoking and stress and is linked to multiple adverse health outcomes through a shared pathway of chronic systemic inflammation. While the health benefits of physical activity have been widely promoted in public health and extensively studied for other systemic conditions, its impact on periodontal health has only recently started to gain attention. This article critically evaluates the current literature on the relationship between physical activity and periodontitis. While cross-sectional studies have shown an inverse association between physical activity levels and periodontitis risk in the general population, clinical oral health surveys of elite athletes with high levels of physical activity have nonetheless revealed poor periodontal conditions. Although causality has not been determined, physical activity could positively impact periodontitis directly, by reducing inflammatory biomarkers, and indirectly, through its modulatory effects on insulin sensitivity, obesity, bone density, stress, and other health promoting behaviors. Given the importance of risk factor control during initial periodontal therapy, understanding the role of physical activity as a potential behavioral risk modifier is paramount. The findings of this review provide an evidence-based overview of how physical activity could influence periodontitis. There is a need for longitudinal cohort studies to verify the temporality of the reported associations and exclude confounders, while interventions are needed to assess the efficacy of physical activity on periodontal treatment outcomes.

Generation of liver metastases in a mouse model using ultrasound-guided intravenous injection.

Here, we present a protocol to generate a murine model of liver metastasis by directly injecting tumor cells into the portal vein under ultrasound guidance. We describe steps for animal and cell preparation and two techniques for injecting tumor cells. One technique is freehand, while the other technique is device-assisted using a 3D-printed prototype device. Finally, we describe tumor surveillance with bioluminescent imaging.

Effort-based decision making in schizotypy and its relationship with amotivation and psychosocial functioning.

Introduction: Suboptimal effort-based decision-making with reduced willingness to expend effort for high-probability/high-value reward is observed in schizophrenia patients and is related to diminished motivation, but is understudied in schizotypy. This study aimed to examine effort-allocation in schizotypy individuals and its association with amotivation and psychosocial functioning. Methods: We recruited 40 schizotypy individuals and 40 demographically-matched healthy controls, based on Schizotypal Personality Questionnaire-Brief (SPQ-B) score (top and bottom 10% SPQ-B scores, respectively), from 2400 young people aged 15-24 years participating a population-based mental health survey in Hong Kong and examined effort-allocation using the Effort Expenditure for Reward Task (EEfRT). Negative / amotivation symptoms and psychosocial functioning were assessed by the Brief Negative Symptom Scale (BNSS) and the Social Functioning and Occupational Assessment Scale (SOFAS), respectively. Schizotypy individuals were categorized into high-amotivation and low-amotivation groups based on a median-split of BNSS amotivation domain score. Results: Our results showed no main group effect (in either two or three-group comparison) on effort task performance. Three-group comparison analyses on selected EEfRT performance indices revealed that high-amotivation schizotypy individuals displayed significantly less increase in effortful options from low-value to high-value reward (reward-difference score) and from low-probability/low-value to high-probability/high-value reward (probability/reward-difference score) than low-amotivation individuals and controls. Correlation analyses demonstrated trend-wise significance between BNSS amotivation domain score and several EEfRT performance indices in schizotypy group. Schizotypy individuals with poorer psychosocial functioning tended to exhibit smaller probability/reward-difference score relative to other two groups. Discussion: Our findings indicate subtle effort-allocation abnormalities in schizotypy individuals with high levels of diminished motivation, and suggest the link between laboratory-based effort-cost measures and real-world functional outcome.

MEK Inhibition Sensitizes Pancreatic Cancer to STING Agonism by Tumor Cell-intrinsic Amplification of Type I IFN Signaling.

PURPOSE: Stimulator of interferon genes (STING) agonists are currently in development for treatment of solid tumors, including pancreatic ductal adenocarcinoma (PDAC). Response rates to STING agonists alone have been promising yet modest, and combination therapies will likely be required to elicit their full potency. We sought to identify combination therapies and mechanisms that augment the tumor cell-intrinsic effect of therapeutically relevant STING agonists apart from their known effects on tumor immunity. EXPERIMENTAL DESIGN: We screened 430 kinase inhibitors to identify synergistic effectors of tumor cell death with diABZI, an intravenously administered and systemically available STING agonist. We deciphered the mechanisms of synergy with STING agonism that cause tumor cell death in vitro and tumor regression in vivo. RESULTS: We found that MEK inhibitors caused the greatest synergy with diABZI and that this effect was most pronounced in cells with high STING expression. MEK inhibition enhanced the ability of STING agonism to induce type I IFN-dependent cell death in vitro and tumor regression in vivo. We parsed NFκB-dependent and NFκB-independent mechanisms that mediate STING-driven type I IFN production and show that MEK signaling inhibits this effect by suppressing NFκB activation. CONCLUSIONS: Our results highlight the cytotoxic effects of STING agonism on PDAC cells that are independent of tumor immunity and that these therapeutic benefits of STING agonism can be synergistically enhanced by MEK inhibition.

18F-FDG PET Visualizes Systemic STING Agonist-Induced Lymphocyte Activation in Preclinical Models.

Stimulator of interferon genes (STING) is a mediator of immune recognition of cytosolic DNA, which plays important roles in cancer, cytotoxic therapies, and infections with certain pathogens. Although pharmacologic STING activation stimulates potent antitumor immune responses in animal models, clinically applicable pharmacodynamic biomarkers that inform of the magnitude, duration, and location of immune activation elicited by systemic STING agonists are yet to be described. We investigated whether systemic STING activation induces metabolic alterations in immune cells that can be visualized by PET imaging. Methods: C57BL/6 mice were treated with systemic STING agonists and imaged with 18F-FDG PET after 24 h. Splenocytes were harvested 6 h after STING agonist administration and analyzed by single-cell RNA sequencing and flow cytometry. 18F-FDG uptake in total splenocytes and immunomagnetically enriched splenic B and T lymphocytes from STING agonist-treated mice was measured by γ-counting. In mice bearing prostate or pancreas cancer tumors, the effects of STING agonist treatment on 18F-FDG uptake, T-lymphocyte activation marker levels, and tumor growth were evaluated. Results: Systemic delivery of structurally distinct STING agonists in mice significantly increased 18F-FDG uptake in the spleen. The average spleen SUVmax in control mice was 1.90 (range, 1.56-2.34), compared with 4.55 (range, 3.35-6.20) in STING agonist-treated mice (P < 0.0001). Single-cell transcriptional and flow cytometry analyses of immune cells from systemic STING agonist-treated mice revealed enrichment of a glycolytic transcriptional signature in both T and B lymphocytes that correlated with the induction of immune cell activation markers. In tumor-bearing mice, STING agonist administration significantly delayed tumor growth and increased 18F-FDG uptake in secondary lymphoid organs. Conclusion: These findings reveal hitherto unknown functional links between STING signaling and immunometabolism and suggest that 18F-FDG PET may provide a widely applicable approach toward measuring the pharmacodynamic effects of systemic STING agonists at a whole-body level and guiding their clinical development.

Effects of the invasive plant garlic mustard (Alliaria petiolata) on bacterial communities in a northern hardwood forest soil.

We compared the effects of the invasive plant Alliaria petiolata (garlic mustard) and 2 native plants on soil bacterial communities in a mature mesophytic forest. Soil samples were collected from plant patches containing either Alliaria or the native plants Allium tricoccum (wild leek) and Gallium triflorum (bedstraw). Since Alliaria litter contains secondary compounds that have reported antimicrobial properties, soil was collected outside the root zone of the plants but within the plant patches such that the soil would have been influenced by the litter of the respective plant species but not by plant roots. DNA was extracted from the soil samples and used to amplify the 16S rRNA gene region using bacterial specific primers. Terminal restriction fragment length polymorphism (TRFLP) profiles of each bacterial community were used to examine differences in bacterial communities among the plant species and between August and April sampling. Bacterial richness, evenness, and diversity were not significantly affected by plant species. Non-metric multidimensional scaling (NMS) suggested that differences existed between August and April sampling, but that plant species litter exerted a much weaker effect on soil bacterial communities. Soil physiochemical conditions were significantly correlated with soil bacterial communities and may underlie the observed seasonal changes in bacterial communities.

Vegetation and soil environment influence the spatial distribution of root-associated fungi in a mature beech-maple forest.

Although the level of diversity of root-associated fungi can be quite high, the effect of plant distribution and soil environment on root-associated fungal communities at fine spatial scales has received little attention. Here, we examine how soil environment and plant distribution affect the occurrence, diversity, and community structure of root-associated fungi at local patch scales within a mature forest. We used terminal restriction fragment length polymorphism and sequence analysis to detect 63 fungal species representing 28 different genera colonizing tree root tips. At least 32 species matched previously identified mycorrhizal fungi, with the remaining fungi including both saprotrophic and parasitic species. Root fungal communities were significantly different between June and September, suggesting a rapid temporal change in root fungal communities. Plant distribution affected root fungal communities, with some root fungi positively correlated with tree diameter and herbaceous-plant coverage. Some aspects of the soil environment were correlated with root fungal community structure, with the abundance of some root fungi positively correlated with soil pH and moisture content in June and with soil phosphorous (P) in September. Fungal distribution and community structure may be governed by plant-soil interactions at fine spatial scales within a mature forest. Soil P may play a role in structuring root fungal communities at certain times of the year.

New antiviral drugs, vaccines and classic public health interventions against SARS coronavirus.

Severe acute respiratory syndrome (SARS) is caused by one of two recently discovered coronaviruses. The virus is emergent from South East (SE) Asian mammals: either the civet cat, a related species or a rat species. The virus has a long incubation period and low reproduction number (R0 value) and hence the first outbreak in 2004 was controlled by hygiene and quarantine. However, the healthcare system was compromised and the economic cost was extremely high. Fortunately, the virus is easily cultivated in Vero E6 cells and therefore the search for new antivirals and vaccines was initiated within weeks of the discovery of the virus using classic techniques of cell culture and electron microscopy. Molecular diagnostics facilitated rapid and accurate diagnosis, a key factor in containing the outbreak. The broad-spectrum molecule ribavirin was used in SE Asia in infected patients alongside corticosteroids. In retrospect, many patients survived due to careful nursing. The only currently accepted intervention is interferon. Coronavirus replicon systems should facilitate rapid screening of new inhibitors and the complex mechanism of viral replication will ensure that drugs are developed against at least five molecular targets, in particular the viral protease.

A throat lozenge containing amyl meta cresol and dichlorobenzyl alcohol has a direct virucidal effect on respiratory syncytial virus, influenza A and SARS-CoV.

A potent virucidal mixture containing amyl metacresol and dichlorobenzyl alcohol at low pH inactivated enveloped respiratory viruses influenza A, respiratory synctial virus (RSV) and severe acute respiratory syndrome coronavirus (SARS-CoV) but not viruses with icosahedral symmetry, such as adenoviruses or rhinoviruses. A titre of approximately 3.5 log10 TCID50 was reduced to below the level of detection within two minutes. Electron microscopy of purified influenza A virus showed extensive clumping and morphological changes in spike configuration after contact with the virucidal mixture, but no overt destruction of the viral membrane. We conclude that, formulated as a lozenge, the mixture could have significant effects in reducing the infectivity of certain infectious viruses in the throat and presumably in cough droplets, thus reducing, theoretically, opportunities for person-to-person transmission.

Effectiveness of group cognitive-behavioral treatment for childhood anxiety in community clinics.

This study evaluated the effectiveness of cognitive-behavioral treatment for childhood anxiety in a community clinic setting in Hong Kong, China. Forty-five clinically-referred children (age 6-11 years) were randomly assigned to either a cognitive-behavioral treatment program or a waitlist-control condition. Children in the treatment condition showed significant reduction in anxiety symptoms-both statistically and clinically-whereas children in the waitlist condition did not. After the waitlist period was over, the control group also received the treatment program and showed a similar reduction in symptoms. For the full sample of 45 children, the effectiveness of the intervention was significant immediately after treatment and in 3- and 6-month follow-ups. In addition, children's anxiety cognition and their ability to cope with anxiety-provoking situations fully mediated the treatment gains. These results offer empirical support for cognitive-behavioral treatment programs in a non-Western cultural context and plausible mediators for how cognitive-behavioral therapy works.