The biobehavioral family model and the family relational assessment protocol: Map and GPS for family systems training.

The Biobehavioral Family Model (BBFM) was developed and evolved as a heuristic research model to support the investigation of pathways by which family relational function impacts individual family member wellbeing and disorder. Recently, the BBFM and its related assessment approach, the Family Relational Process Assessment Protocol (FRAP), have emerged as tools for clinical practice and training. The BBFM model will be presented, along with definitions of the dimensions constructed in the model, and research evidence in support of the model. To illustrate how the BBFM and FRAP are used in training, instructions for conducting the FRAP will be presented. Then, transcripts from two contrasting families participating in one of the interaction tasks will illustrate how, in training, the FRAP is interpreted through the BBFM lens to illuminate how these patterns of family relationship impact the identified patient. Finally, three applications of this training approach will exemplify the use of the BBFM and FRAP in the context of a Child and Adolescent Psychiatry Fellowship, a Family Medicine Fellowship, and a Family Therapy Training Program in Istanbul, Turkey. Limitations and future directions for the application of the BBFM in the exploration of multicultural aspects of family function for clinical and training purposes will be discussed.

Mechanisms of improved body composition among perimenopausal women practicing Meditative Movement: a proposed biobehavioral model.

OBJECTIVES: Weight gain and unfavorable body composition are prevalent among midlife/older women throughout menopause. These shifts may negatively impact health, well-being, and longevity. Efforts to attenuate weight and body composition changes are traditionally driven by manipulation of diet and/or exercise; however, sustained results are limited, possibly because the full spectrum of biobehavioral systems is not addressed by diet and exercise alone. We propose a biobehavioral model detailing mechanisms of body composition decline among perimenopausal women and the associated components of Meditative Movement (ie, tai chi, qigong, yoga) that address each of these factors. METHODS: Based on our previous work and extensive review of the literature, we developed a multifactorial and multidimensional biobehavioral model including factors that most directly relate to body composition among perimenopausal women: 1) psychological (ie, stress and mood, mindfulness and self-compassion, body awareness), 2) behavioral (ie, sleep, physical activity, eating behaviors), and 3) physiological (ie, cortisol, estrogen). Relationships between each factor, Meditative Movement practice components, and predicted effects on body composition were explored in detail. RESULTS: Our model describes select psychological, behavioral, and physiological factors, and potential mechanistic pathways of Meditative Movement practice driving improved changes in body composition and weight outcomes for perimenopausal women. CONCLUSIONS: The proposed model details a novel, evidence-supported means to reduce the risk of deleterious shifts in body composition throughout perimenopause and menopause thereafter. We suggest that these changes may occur directly and/or indirectly through psychological, behavioral, and physiological mechanisms that facilitate the desired changes in body composition.

Testing a Biobehavioral Model of Food Insecurity and Chronic Disease in Hispanic Older Adolescents.

The biobehavioral model of food insecurity and chronic disease posits that stress perpetuates the cycle of food insecurity and chronic disease, in part, through changes in eating behaviors and weight gain. The current study conducted a preliminary test of the biobehavioral model in a sample of Hispanic older adolescents. It was hypothesized that older adolescents experiencing food insecurity would report greater depressive symptoms, which would be associated with more disordered eating, which would be associated with worse cardiometabolic indicators. Hispanic older adolescents (N = 113; 60% female; 15-21 years with mean age of 19.1; BMImean = 24.4) completed self-report baseline measures of food insecurity, depression, and disordered eating behaviors as part of a larger experimental study. Anthropometrics and body composition, blood pressure, heart rate, and resting metabolic rate were objectively measured. Hypotheses were tested using structural equation modeling. Experiencing food insecurity was associated with more disordered eating (b = 2.20, p = 0.032). Greater depressive symptoms were associated with more disordered eating (b = 0.28, p = 0.025) and worse cardiometabolic indicators (b = 0.15, p = 0.017). The full biobehavioral model, however, was not supported. Findings underscore the complex interaction of social and psychological functioning and physical health.

A jury of scientists: Formal education in biobehavioral sciences reduces the odds of punitive criminal sentencing.

This study examines how formal education in biological and behavioral sciences may impact punishment intuitions (views on criminal sentencing, free will, responsibility, and dangerousness) in cases involving neurobiological evidence. In a survey experiment, we compared intuitions between biobehavioral science and non-science university graduates by presenting them with a baseline case without a neurobiological explanation for offending followed by one of two cases with a neurobiological explanation (described as either innate or acquired biological influences to offending). An ordinal logistic regression indicated that both science and non-science graduates selected significantly more severe punishments for the baseline case as compared to when an innate neurobiological explanation for offending was provided. However, across all cases, science graduates selected significantly less severe sentences than non-science graduates, and only science graduates' decisions were mediated by free will and responsibility attributions. Findings are discussed in relation to scientific understandings of behavior, the impact of science education on attitudes towards punishment, and potential criminal-legal implications.

Bisdemethoxycurcumin Induces Cell Apoptosis and Inhibits Human Brain Glioblastoma GBM 8401/Luc2 Cell Xenograft Tumor in Subcutaneous Nude Mice In Vivo.

Bisdemethoxycurcumin (BDMC) has biological activities, including anticancer effects in vitro; however, its anticancer effects in human glioblastoma (GBM) cells have not been examined yet. This study aimed to evaluate the tumor inhibitory effect and molecular mechanism of BDMC on human GBM 8401/luc2 cells in vitro and in vivo. In vitro studies have shown that BDMC significantly reduced cell viability and induced cell apoptosis in GBM 8401/luc2 cells. Furthermore, BDMC induced apoptosis via inhibited Bcl-2 (anti-apoptotic protein) and increased Bax (pro-apoptotic proteins) and cytochrome c release in GBM 8401/luc2 cells in vitro. Then, twelve BALB/c-nude mice were xenografted with human glioblastoma GBM 8401/luc2 cancer cells subcutaneously, and the xenograft nude mice were treated without and with BDMC (30 and 60 mg/kg of BDMC treatment) every 3 days. GBM 8401/luc2 cell xenografts experiment showed that the growth of the tumors was significantly suppressed by BDMC administration at both doses based on the reduction of tumor size and weights. BDMC did not change the body weight and the H&E histopathology analysis of liver samples, indicating that BDMC did not induce systemic toxicity. Meanwhile, treatment with BDMC up-regulated the expressions of BAX and cleaved caspase-3, while it down-regulated the protein expressions of Bcl-2 and XIAP in the tumor tissues compared with the control group. This study has demonstrated that BDMC presents potent anticancer activity on the human glioblastoma GBM 8401/luc2 cell xenograft model by inducing apoptosis and inhibiting tumor cell proliferation and shows the potential for further development to the anti-GBM cancer drug.

Childhood maltreatment and its role in the development of pain and psychopathology.

Childhood maltreatment represents a form of trauma capable of altering fundamental neurobiological properties and negatively impacting neurodevelopmental processes. An outcome of childhood maltreatment is the emergence of psychopathology, which might become evident during childhood or adolescence, but might also project into adulthood. In this Review, we propose a biobehavioural framework in which childhood maltreatment and the associated aberrant neurobiological mechanisms and behavioural processes additionally lead to the onset of altered pain processing and, ultimately, the existence of pain syndromes. Considering that subpopulations of maltreated children show preserved function and minimal psychiatric or pain symptoms, compensatory mechanisms-perhaps instilled by robust psychosocial support systems-are also discussed. We present validated tools and experimental methods that could facilitate better comprehension of the interactions between childhood maltreatment, psychopathology, and pain. Such tools and approaches can in parallel be implemented to monitor abnormal pain-related processes and potentially guide early intervention strategies in cases of childhood maltreatment.

An application of the Biobehavioral Family Model: Examining the impact of maternal depression on child asthma mediated by insecure attachment and child depression.

OBJECTIVE: Child asthma disparities are prevalent in socio-economically stressed single-parent families. Stress impacts childhood asthma mediated by immune and autonomic pathways, but specific family stress pathways are not well established. This study tests the hypothesis, derived from a version of the Biobehavioral Family Model, that single parent maternal depression impacts child asthma mediated by insecure attachment and child depression. METHODS: In a cross-sectional study, children with asthma (age 7-17 years old) from a socio-economically disadvantaged population and their single parent mothers (N = 202) were assessed for depression and attachment security. Child asthma disease activity was assessed by symptom report and lung function tests. Structural equation modeling (SEM) was used to test a model in which caregiver depression impacts child asthma disease activity mediated by insecure attachment and child depression. RESULTS: SEM results indicated that maternal depression statistically predicted child depression (ß = 0.21, p < 0.01) and insecure mother-child attachment (ß = 0.17, p < 0.05). In addition, insecure attachment statistically predicted child depression (ß = 0.50, p < 0.001). Child depression mediated the adverse effects of maternal depression and insecure attachment on child asthma disease activity (ß = 0.43, p < 0.01). There was no direct effect of insecure attachment on child asthma. CONCLUSION: In single-parent families, maternal depression may impact child asthma disease activity, mediated serially by insecure attachment and child depression. Longitudinal and/or intervention studies are needed to establish a causal effect. These findings suggest that caregiver depression and parent-child relationships may be important targets for family intervention. These interventions may help improve child asthma outcomes and reduce health disparities.

Predictive waves in the autism-schizophrenia continuum: A novel biobehavioral model.

The brain is a predictive machine. Converging data suggests a diametric predictive strategy from autism spectrum disorders (ASD) to schizophrenic spectrum disorders (SSD). Whereas perceptual inference in ASD is rigidly shaped by incoming sensory information, the SSD population is prone to overestimate the precision of their priors' models. Growing evidence considers brain oscillations pivotal biomarkers to understand how top-down predictions integrate bottom-up input. Starting from the conceptualization of ASD and SSD as oscillopathies, we introduce an integrated perspective that ascribes the maladjustments of the predictive mechanism to dysregulation of neural synchronization. According to this proposal, disturbances in the oscillatory profile do not allow the appropriate trade-off between descending predictive signal, overweighted in SSD, and ascending prediction errors, overweighted in ASD. These opposing imbalances both result in an ill-adapted reaction to external challenges. This approach offers a neuro-computational model capable of linking predictive coding theories with electrophysiological findings, aiming to increase knowledge on the neuronal foundations of the two spectra features and stimulate hypothesis-driven rehabilitation/research perspectives.

Deregulated Expression of miR-483-3p Serves as a Diagnostic Biomarker in Severe Pneumonia Children with Respiratory Failure and Its Predictive Value for the Clinical Outcome of Patients.

Severe pneumonia in children is a group of inflammatory diseases of respiratory tract caused by pathogenic microorganisms. Increasing evidence suggested the crucial effects of microRNA on inflammatory diseases. This study aimed to reveal the expression and role of miR-483-3p in the serum of children with severe pneumonia, and to explore the effect of miR-483-3p on the biological function of lipopolysaccharide (LPS)-induced MRC-5 cells. MRC-5 cells were disposed with LPS to construct an in vitro pneumonia cell model. The relative expression level of miR-483-3p was measured by qRT-PCR. ROC curve was used to evaluate the diagnostic value of miR-483-3p in severe pneumonia. The Kaplan-Meier curve was performed to test the characteristics of survival distribution of different miRNA classifications. Cell viability and apoptosis were performed by CCK-8 assay and flow cytometry. IL-1ß, TNF-α, and IL-6 were detected by ELISA. Luciferase reporter gene assay and western blot analysis were performed to detect the interaction between miR-483-3p and IGF-1. The expression of serum miR-483-3p in severe pneumonia patients was higher than in controls. The AUC value of the ROC curve was 0.919, indicating that miR-483-3p had diagnostic value for severe pneumonia. The survival curve showed that patients with high expression of miR-483-3p had higher mortality. Cell viability and apoptosis assay showed that overexpression of miR-483-3p suppressed cell proliferation and promoted apoptosis. And upregulation of miR-483-3p promoted generation of inflammatory cytokines. Luciferase report gene assay and western blot assay both illustrated that IGF-1 might be the target gene of miR-483-3p. Serum miR-483-3p can be used as a biomarker for the diagnosis of severe pneumonia. High expression of miR-483-3p promoted the development of severe pneumonia.

Non-invasive quantification of the mitochondrial redox state in livers during machine perfusion.

Ischemia reperfusion injury (IRI) is a critical problem in liver transplantation that can lead to life-threatening complications and substantially limit the utilization of livers for transplantation. However, because there are no early diagnostics available, fulminant injury may only become evident post-transplant. Mitochondria play a central role in IRI and are an ideal diagnostic target. During ischemia, changes in the mitochondrial redox state form the first link in the chain of events that lead to IRI. In this study we used resonance Raman spectroscopy to provide a rapid, non-invasive, and label-free diagnostic for quantification of the hepatic mitochondrial redox status. We show this diagnostic can be used to significantly distinguish transplantable versus non-transplantable ischemically injured rat livers during oxygenated machine perfusion and demonstrate spatial differences in the response of mitochondrial redox to ischemia reperfusion. This novel diagnostic may be used in the future to predict the viability of human livers for transplantation and as a tool to better understand the mechanisms of hepatic IRI.

Correlates of attendance at community engagement meetings held in advance of bio-behavioral research studies: A longitudinal, sociocentric social network study in rural Uganda.

BACKGROUND: Community engagement is central to the conduct of health-related research studies as a way to determine priorities, inform study design and implementation, increase recruitment and retention, build relationships, and ensure that research meets the goals of the community. Community sensitization meetings, a form of community engagement, are often held prior to the initiation of research studies to provide information about upcoming study activities and resolve concerns in consultation with potential participants. This study estimated demographic, health, economic, and social network correlates of attendance at community sensitization meetings held in advance of a whole-population, combined behavioral, and biomedical research study in rural Uganda. METHODS AND FINDINGS: Research assistants collected survey data from 1,630 adults participating in an ongoing sociocentric social network cohort study conducted in a rural region of southwestern Uganda. These community survey data, collected between 2016 and 2018, were linked to attendance logs from community sensitization meetings held in 2018 and 2019 before the subsequent community survey and community health fair. Of all participants, 264 (16%) attended a community sensitization meeting before the community survey, 464 (28%) attended a meeting before the community health fair, 558 (34%) attended a meeting before either study activity (survey or health fair), and 170 (10%) attended a meeting before both study activities (survey and health fair). Using multivariable Poisson regression models, we estimated correlates of attendance at community sensitization meetings. Attendance was more likely among study participants who were women (adjusted relative risk [ARR]health fair = 1.71, 95% confidence interval [CI], 1.32 to 2.21, p < 0.001), older age (ARRsurvey = 1.02 per year, 95% CI, 1.01 to 1.02, p < 0.001; ARRhealth fair = 1.02 per year, 95% CI, 1.01 to 1.02, p < 0.001), married (ARRsurvey = 1.74, 95% CI, 1.29 to 2.35, p < 0.001; ARRhealth fair = 1.41, 95% CI, 1.13 to 1.76, p = 0.002), and members of more community groups (ARRsurvey = 1.26 per group, 95% CI, 1.10 to 1.44, p = 0.001; ARRhealth fair = 1.26 per group, 95% CI, 1.12 to 1.43, p < 0.001). Attendance was less likely among study participants who lived farther from meeting locations (ARRsurvey = 0.54 per kilometer, 95% CI, 0.30 to 0.97, p = 0.041; ARRhealth fair = 0.57 per kilometer, 95% CI, 0.38 to 0.86, p = 0.007). Leveraging the cohort's sociocentric design, social network analyses suggested that information conveyed during community sensitization meetings could reach a broader group of potential study participants through attendees' social network and household connections. Study limitations include lack of detailed data on reasons for attendance/nonattendance at community sensitization meetings; achieving a representative sample of community members was not an explicit aim of the study; and generalizability may not extend beyond this study setting. CONCLUSIONS: In this longitudinal, sociocentric social network study conducted in rural Uganda, we observed that older age, female sex, being married, membership in more community groups, and geographical proximity to meeting locations were correlated with attendance at community sensitization meetings held in advance of bio-behavioral research activities. Information conveyed during meetings could have reached a broader portion of the population through attendees' social network and household connections. To ensure broader input and potentially increase participation in health-related research studies, the dissemination of research-related information through community sensitization meetings may need to target members of underrepresented groups.

Cognitive bias analysis of young novice drivers' observation abilities-A questionnaire-based study.

Observation ability, which is the basis of following decision-making and vehicle manipulation behaviour, is of great importance while driving. However, the subject self-cognition and objective assessment of driving ability are usually different, especially for the young novice drivers. In this paper, drivers' observation abilities for both static traffic signs and markings and dynamic surrounding vehicles were investigated based on questionnaire data. Effects of gender and driving characteristics (driving year, driving frequency, driving time) on drivers' observation abilities were verified by ANOVA analysis and structural equation model (SEM) from two aspects: drivers' self-assessment scores (self-assessment) and mutual assessment scores (evaluated by others). Significant difference could be found between all the factors and drivers' self-assessment scores, while only driving year had a significant effect on drivers' mutual assessment scores. Besides, cognitive bias was found between all the driving year groups. It seemed that drivers with driving experience less than one year were always overconfident with their driving abilities. And drivers with driving experience more than three years usually gave the most conservative assessment scores for themselves and others. With more exposures to various traffic conditions, experienced drivers are more aware of their limitations on observing surrounding information, while young novice drivers still not realized their limitations on observing traffic signs and other vehicles in a right way.

Depressive hypertension: A proposed human endotype of brain/gut microbiome dysbiosis.

BACKGROUND: Hypertension (HTN) is frequently linked with depression (DEP) in adults with cardiovascular disease (CVD), yet the underlying mechanism and successful management remain elusive. We approached this knowledge gap through the lens that humans are eukaryote-prokaryote "meta-organisms," such that cardiovascular disease dysregulation is a mosaic disorder involving dysbiosis of the gut. We hypothesized that patients diagnosed with hypertension plus depression harbor a unique gut microbial ecology with attending functional genomics engaged with their hosts' gut/brain axis physiology. METHODS: Stool microbiome DNA was analyzed by whole metagenome shotgun sequencing in 54 subjects parsed into cohorts diagnosed with HTN only (N = 18), DEP only (N = 7), DEP plus HTN (DEP-HTN) (N = 8), or reference subjects with neither HTN nor DEP (N = 21). A novel battery of machine-learning multivariate analyses of de-noised data yielded effect sizes and permutational covariance-based dissimilarities that significantly differentiated the cohorts (false discovery rate (FDR)-adjusted P ≤ .05); data clustering within 95% confidence interval). RESULTS: Metagenomic significant differences extricated the four cohorts. Data of the cohort exhibiting DEP-HTN were germane to the interplay of central control of blood pressure concomitant with the neuropathology of depressive disorders. DEP-HTN gut bacterial community ecology was defined by co-occurrence of Eubacterium siraeum, Alistipes obesi, Holdemania filiformis, and Lachnospiraceae bacterium 1.1.57FAA with Streptococcus salivariu. The corresponding microbial functional genomics of DEP-HTN engaged pathways degrading GABA and beneficial short chain fatty acids (SCFA), and are associated with enhanced sodium absorption and inflammasome induction. CONCLUSIONS: These data suggest a new putative endotype of hypertension, which we denote "depressive-hypertension" (DEP-HTN), for which we posit a model that is distinctive from either HTN alone or DEP alone. An "endotype" is a subtype of a heterogeneous pathophysiological mechanism. The DEP-HTN model incorporates a unique signature of microbial taxa and functional genomics with crosstalk that putatively intertwines host pathophysiology involving the gastrointestinal tract with disruptions in central control of blood pressure and mood. The DEP-HTN endotype model engages cardiology with gastroenterology and psychiatry, providing a proof-of-concept foundation to explore future treatments, diagnosis, and prevention of HTN-coupled mood disorders.

The biopsychosocial-digital continuum of foot orthosis practice and research: the VALUATOR model.

Foot orthoses have been used for decades despite uncertainty surrunding their therapeutic efficacy. Orthoses have been used exclusively to affect neuro-biomechanical input and outcome variables, however, there is emerging evidence that therapeutic efficacy may be affected by a psychological stimulus. Critical appraisal of the literature highlights that there is no holistic model upon which foot orthosis practice is taught, practised nor investigated. This paper introduces a conceptual model of foot orthosis practice (Value Based Foot Orthosis Practice (VALUATOR) model) that embraces a broader range of factors that are pertinent to orthosis practice, incorporating contemporary health service behaviours and values into orthosis practice for the first time.Within the VALUATOR model, foot orthosis design and clinical value is considered along a bio-psycho-social-digital continuum that reflects the reality of foot orthosis practice. The model contextualises the variable outcomes that are observed in research and practice within 6 key areas: 1) value, 2) person-centered approach, 3) zone of optimal bio-psycho-social stress, 4) bio-psycho-social assessment, 5) monitoring, 6) primary and secondary clinical strategies.The VALUATOR model is targeted at students, lecturers, scientists and practitioners and includes carefully chosen terminology to support a robust basis for educational and scientific discussion. It is believed that it provides a contemporary viewpoint and a structured conceptual metaphor that builds on existing evidence from a wide range of sources, invites constructive intellectual debate, and is anchored in the experiences of practitioners too. Stress testing the VALUATOR model will help determine its model and support further developments and evolution of orthotic practice in a evidence based way.

The model crisis, or how to have critical promiscuity in the time of Covid-19.

During the past forty years, statistical modelling and simulation have come to frame perceptions of epidemic disease and to determine public health interventions that might limit or suppress the transmission of the causative agent. The influence of such formulaic disease modelling has pervaded public health policy and practice during the Covid-19 pandemic. The critical vocabulary of epidemiology, and now popular debate, thus includes R0, the basic reproduction number of the virus, 'flattening the curve', and epidemic 'waves'. How did this happen? What are the consequences of framing and foreseeing the pandemic in these modes? Focusing on historical and contemporary disease responses, primarily in Britain, I explore the emergence of statistical modelling as a 'crisis technology', a reductive mechanism for making rapid decisions or judgments under uncertain biological constraint. I consider how Covid-19 might be configured or assembled otherwise, constituted as a more heterogeneous object of knowledge, a different and more encompassing moment of truth - not simply as a measured telos directing us to a new normal. Drawing on earlier critical engagements with the AIDS pandemic, inquiries into how to have 'theory' and 'promiscuity' in a crisis, I seek to open up a space for greater ecological, sociological, and cultural complexity in the biopolitics of modelling, thereby attempting to validate a role for critique in the Covid-19 crisis.

Etiological Overlap Between Sex Under the Influence and Number of Lifetime Sexual Partners.

Drug and alcohol use is associated with risky sexual behavior (RSB). It is unclear whether this association is due to correlated liabilities (e.g., third variables influencing both traits), or whether use of drugs and alcohol during sexual decision making increases RSB. This study addresses this question by fitting a series of biometrical models using over 800 twin pairs assessed in early adulthood (m = 25.21 years). Measures included an index of sex under the influence (e.g., frequency that drugs or alcohol affect sexual decision making), number of lifetime sexual partners, and a general measure of substance use. Analyses suggest the covariance among these measures is explained by both genetic and environmental correlated liabilities. The overlap was not specific to sex under the influence, but was shared with a measure of general substance use. Models testing necessary but not sufficient parameters for direction of causation suggest that sex under the influence is unlikely to cause an increase in RSB; more evidence for reverse causation was found.

A review of current strategies to improve HIV prevention and treatment in sexual and gender minority Latinx (SGML) communities.

INTRODUCTION: The HIV epidemic continues to disproportionately impact sexual and gender minority Latinxs (SGML). Several syndemic conditions have been linked with HIV acquisition and transmission among SGML including immigration, discrimination, environmental racism, substance use, and mental health. AREAS COVERED: We provide a summary of biomedical, behavioral, and social/structural interventions to reduce risks for acquiring HIV and improve outcomes along the HIV care continuum among SGML. We also discuss intervention approaches and opportunities that respond at the intersection of HIV and COVID-19 prevention and treatment. EXPERT OPINION: There is a dire need for the combination of biomedical, behavioral, and social/structural interventions to reduce risks for acquiring HIV and improve outcomes along the HIV care continuum. Interventions and combination approaches should be driven by community-based participatory action research. The inclusion of community members in all stages of the research process can assure successful implementation of program activities and deliverables, including the provision of culturally and linguistically appropriate services. Given the current COVID-19 pandemic, which is disproportionately impacting individuals living with HIV and other comorbidities, the elderly, and under-resourced communities with a ferocity not seen in other communities, intervention approaches that respond at the intersection of HIV and COVID-19 prevention and treatment are also urgently needed.

Deviations in criminal filings of child abuse and neglect during COVID-19 from forecasted models: An analysis of the state of Oklahoma, USA.

BACKGROUND: The COVID-19 pandemic has contributed to risk factors for child abuse and neglect and disrupted conventional abuse surveillance. OBJECTIVE: The goal of this study was to assess how counts of criminal charges have been affected by COVID-19 social distancing measures and related policy changes. PARTICIPANTS AND SETTING: This study used publicly available court filings pertaining to child abuse and neglect from Jan 1, 2010 to June 30, 2020. METHODS: Autoregressive integrated moving average (ARIMA) algorithms were constructed with case data from January 2010 to January 2020 to forecast trends in criminal charges for February to June 2020. These forecasted values were then compared to actual charges filed for this time period. RESULTS: Criminal cases filed between February and June 2020, had an overall 25.7 percent lower average than forecasted. All individual months had progressively lower cases than forecasted with the exception of March. June had the largest deviation from forecasted with 60.1 percent fewer cases than predicted. CONCLUSIONS: Although risk factors for child abuse have increased due to COVID-19, these findings demonstrate a declining trend in child abuse charges. Rather than a decreasing incidence of child abuse and neglect, it is more likely that less cases are being reported. The results warrant immediate action and further investigation in order to address the dangers this pandemic poses for children in abusive situations.

Development of a Testing Funnel for Identification of Small-Molecule Modulators Targeting Secretin Receptors.

The secretin receptor (SCTR), a prototypical class B G protein-coupled receptor (GPCR), exerts its effects mainly by activating Gαs proteins upon binding of its endogenous peptide ligand secretin. SCTRs can be found in a variety of tissues and organs across species, including the pancreas, stomach, liver, heart, lung, colon, kidney, and brain. Beyond that, modulation of SCTR-mediated signaling has therapeutic potential for the treatment of multiple diseases, such as heart failure, obesity, and diabetes. However, no ligands other than secretin and its peptide analogs have been described to regulate SCTRs, probably due to inherent challenges in family B GPCR drug discovery. Here we report creation of a testing funnel that allowed targeted detection of SCTR small-molecule activators. Pursuing the strategy to identify positive allosteric modulators (PAMs), we established a unique primary screening assay employing a mixture of three orthosteric stimulators that was compared in a screening campaign testing 12,000 small-molecule compounds. Beyond that, we developed a comprehensive set of secondary assays, such as a radiolabel-free target engagement assay and a NanoBiT (NanoLuc Binary Technology)-based approach to detect ß-arrestin-2 recruitment, all feasible in a high-throughput environment as well as capable of profiling ligands and hits regarding their effect on binding and receptor function. This combination of methods enabled the discovery of five promising scaffolds, four of which have been validated and further characterized with respect to their allosteric activities. We propose that our results may serve as starting points for developing the first in vivo active small molecules targeting SCTRs.

Values encoded in orbitofrontal cortex are causally related to economic choices.

In the eighteenth century, Daniel Bernoulli, Adam Smith and Jeremy Bentham proposed that economic choices rely on the computation and comparison of subjective values1. This hypothesis continues to inform modern economic theory2 and research in behavioural economics3, but behavioural measures are ultimately not sufficient to verify the proposal4. Consistent with the hypothesis, when agents make choices, neurons in the orbitofrontal cortex (OFC) encode the subjective value of offered and chosen goods5. Value-encoding cells integrate multiple dimensions6-9, variability in the activity of each cell group correlates with variability in choices10,11 and the population dynamics suggests the formation of a decision12. However, it is unclear whether these neural processes are causally related to choices. More generally, the evidence linking economic choices to value signals in the brain13-15 remains correlational16. Here we show that neuronal activity in the OFC is causal to economic choices. We conducted two experiments using electrical stimulation in rhesus monkeys (Macaca mulatta). Low-current stimulation increased the subjective value of individual offers and thus predictably biased choices. Conversely, high-current stimulation disrupted both the computation and the comparison of subjective values, and thus increased choice variability. These results demonstrate a causal chain linking subjective values encoded in OFC to valuation and choice.