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Frameworks of emotional development have tended to focus on how environmental factors shape children's emotion understanding. However, individual experiences of emotion represent a complex interplay between both external environmental inputs and internal somatovisceral signaling. Here, we discuss the importance of afferent signals and coordination between central and peripheral mechanisms in affective response processing. We propose that incorporating somatovisceral theories of emotions into frameworks of emotional development can inform how children understand emotions in themselves and others. We highlight promising directions for future research on emotional development incorporating this perspective, namely afferent cardiac processing and interoception, immune activation, physiological synchrony, and social touch.

OBJECTIVE To determine whether shock index (SI) positively correlates with percentage blood loss and negatively correlates with cardiac output (CO) in a canine hemorrhagic shock model and whether SI and metabolic markers may be used as end point targets for resuscitation. ANIMALS 8 healthy Beagles. PROCEDURES Between September and December 2021, dogs underwent general anesthesia for experimental induction of hypotensive shock, with the total volume of blood removed, CO, heart rate, systolic blood pressure, base excess, blood pH, and concentrations of hemoglobin, lactate, ionized calcium recorded, and SI calculated at 4 time points (TPs): after anesthetic induction when the dog had been stable for 10 minutes (TP1), 10 minutes after the mean arterial pressure stabilized to a target of 40 mm Hg following jugular removal of up to 60% blood volume to induce hemorrhagic shock (TP2), 10 minutes after autotransfusion of 50% of the removed blood (TP3), and 10 minutes after autotransfusion of the remaining 50% of the removed blood (TP4). RESULTS Mean SI increased between TP1 (1.08 ± 0.35) and TP2 (1.90 ± 0.73) and did not return to the prehemorrhage values for TP3 or TP4. SI correlated positively with percentage blood loss (r = 0.583) and negatively with CO (r = –0.543). CLINICAL RELEVANCE An increase in SI may support diagnosis of hemorrhagic shock; however, SI cannot be used as the sole end point of resuscitation. Significant differences in blood pH, base excess, and lactate concentration suggested they may be useful markers of hemorrhagic shock and need for blood transfusion.

Successful management of opioid withdrawal improves long-term treatment outcomes and reduces opioid use-related morbidity and mortality. Mechanistically supported pharmacotherapeutic approaches are needed to effectively manage acute and protracted opioid withdrawal. Buspirone is a D2 antagonist and 5-HT1a agonist that may decrease opioid withdrawal. Individuals (

To explore changes in student food security status (FSS) during college enrollment and correlates of those changes.Two cross-sectional surveys (2016 and 2019).Undergraduates (n = 338) at a public university who completed both surveys.Food security status (US Department of Agriculture 10- and 18-item measures), demographics, and grade point average (GPA).Chi-square tests of goodness of fit for representativeness, McNemar-Bowker and paired samples Wilcoxon signed rank test for within-student FSS differences over time, logistic regression for the relationship between demographics and FSS over time, and ANCOVA for the relationship between FSS and GPA. Critical P ≤ 0.05 unless otherwise noted.The prevalence of food insecurity was 22.4% in 2016 and 41.0% in 2019, and the McNemar-Bowker test indicated a significant asymmetrical relationship in FSS over time (P0.001). Almost half of the respondents (47.0%) reported experiencing food insecurity at least once. In multivariate analyses controlling for other demographic variables, first-generation students had the most consistent risk of food insecurity with lower FSS in 2016 (P0.001) and 2019 (P0.001), and they were more likely to have worsened FSS over time (P = 0.05). Food insecurity at either time was related to a lower 2019 GPA (P0.001).Food security status measured cross-sectionally cannot capture changes in student FSS, which many students may experience. Longitudinal research is needed to better understand the role of demographic and student factors in FSS changes over time. Food resources should be offered to all students, as many will need them at some point.

Initial experiences with drugs may influence an individual’s motivations for continued use. This study evaluated the relationship between subjective effects elicited by an individual’s first use of alcohol or cannabis, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) alcohol use disorder (AUD) or cannabis use disorder (CUD) severity, and behavioral economic demand for alcohol or cannabis. Self-reports of initial subjective effects associated with drugs were analyzed for N = 463 participants whose first substance use was either alcohol or cannabis. The likelihood that a particular subjective effect at the time of first use was associated with current AUD/CUD was assessed using ordinal logistic regression with subjective effects as predictors of DSM-5 severity. Behavioral economic demand was assessed using a hypothetical purchase task in which participants indicated their hypothetical consumption of alcohol or cannabis as a function of price. Significant associations were observed for initial subjective effects elicited by alcohol or cannabis and increased DSM-5 severity: (alcohol) relief (OR = 2.52 [95% CI 1.51–4.25], p = .0005) and (cannabis) energetic (OR = 2.31 [95% CI 3.27–55.5], p = .0004). The mean (±SEM) P(max) value for the alcohol subgroup endorsing relief ($96.22 ± $26.48) was significantly greater than the P(max) value for the alcohol subgroup not endorsing relief ($33.81 ± $12.93), t(237) = 2.276, p = .0237. These results suggest that the initial subjective effects associated with a given substance may predict the development and/or severity of substance misuse and substance use disorders (SUDs). These findings are consistent with anecdotal reports that persons with SUD feel energized by the use of substances whereas persons without SUD do not report experiencing such subjective effects upon first use.

Background Higher doses of rifampicin may improve treatment outcomes and reduce the duration of tuberculosis (TB) therapy. However, drug–drug interactions with antiretroviral therapy (ART) and safety in people with human immunodeficiency virus (HIV) have not been evaluated. Methods This was a randomized, open-label trial where newly diagnosed TB patients were randomized to higher (35 mg/kg) or standard (10 mg/kg) daily-dose rifampicin. ART treatment–naive patients were randomized to dolutegravir- or efavirenz-based ART. At week 6, trough dolutegravir or mid-dose efavirenz plasma concentrations were assayed. HIV viral load was measured at week 24. Results Among 128 patients randomized, the median CD4 count was 191 cells/mm3. The geometric mean ratio (GMR) for trough dolutegravir concentrations on higher- vs standard-dose rifampicin was 0.57 (95% confidence interval [CI], .34–.97; P = .039) and the GMR for mid-dose efavirenz was 0.63 (95% CI, .38–1.07; P = .083). There was no significant difference in attainment of targets for dolutegravir trough or efavirenz mid-dose concentrations between rifampicin doses. The incidence of HIV treatment failure at week 24 was similar between rifampicin doses (14.9% vs 14.0%, P = .901), as was the incidence of drug-related grade 3–4 adverse events (9.8% vs 6%). At week 8, fewer patients remained sputum culture positive on higher-dose rifampicin (18.6% vs 37.0%, P = .063). Conclusions Compared with standard-dose rifampicin, high-dose rifampicin reduced dolutegravir and efavirenz exposures, but HIV suppression was similar across treatment arms. Higher-dose rifampicin was well tolerated among people with HIV and associated with a trend toward faster sputum culture conversion. Clinical Trials Registration NCT03982277.

SAR on NRF2 inhibitor MSU38225 has led to a compound that inhibits expression of NRF2 target genes, reduces proliferation of lung cancer cells through G2/M arrest, and lowers cell migration.

BackgroundThe National Institute for Health and Care Excellence (NICE) 2020 guidelines recommends aspirin for colorectal cancer prevention for people with Lynch syndrome. Strategies to change practice should be informed by understanding the factors influencing prescribing.AimTo investigate the optimal type and level of information to communicate with GPs to increase willingness to prescribe aspirin.Design and settingGPs in England and Wales (n= 672) were recruited to participate in an online survey with a 23factorial design. GPs were randomised to one of eight vignettes describing a hypothetical patient with Lynch syndrome recommended to take aspirin by a clinical geneticist.MethodAcross the vignettes, the presence or absence of three types of information was manipulated: 1) existence of NICE guidance; 2) results from the CAPP2 trial; 3) information comparing risks/benefits of aspirin. The main effects and all interactions on the primary (willingness to prescribe) and secondary outcomes (comfort discussing aspirin) were estimated.ResultsThere were no statistically significant main effects or interactions of the three information components on willingness to prescribe aspirin or comfort discussing harms and benefits. In total, 80.4% (540/672) of GPs were willing to prescribe, with 19.7% (132/672) unwilling. GPs with prior awareness of aspirin for preventive therapy were more comfortable discussing the medication than those unaware (P= 0.031).ConclusionIt is unlikely that providing information on clinical guidance, trial results, and information comparing benefits and harms will increase aspirin prescribing for Lynch syndrome in primary care. Alternative multilevel strategies to support informed prescribing may be warranted.

Patients with multiple myeloma (MM) mount suboptimal neutralizing antibodies (nAb) following 2 doses of SARS-CoV-2 mRNA vaccines. Currently, circulating SARS-CoV-2 variants of concern (VOC) carry the risk of breakthrough infections. We evaluated immune recognition of current VOC including BA.1, BA.2, and BA.5 in 331 racially representative patients with MM following 2 or 3 doses of mRNA vaccines. The third dose increased nAbs against WA1 in 82%, but against BA variants in only 33% to 44% of patients. Vaccine-induced nAbs correlated with receptor-binding domain (RBD)–specific class-switched memory B cells. Vaccine-induced spike-specific T cells were detected in patients without seroconversion and cross-recognized variant-specific peptides but were predominantly CD4+ T cells. Detailed clinical/immunophenotypic analysis identified features correlating with nAb/B/T-cell responses. Patients who developed breakthrough infections following 3 vaccine doses had lower live-virus nAbs, including against VOC. Patients with MM remain susceptible to SARS-CoV-2 variants following 3 vaccine doses and should be prioritized for emerging approaches to elicit variant-nAb and CD8+ T cells.Significance:Three doses of SARS-CoV-2 mRNA vaccines fail to yield detectable VOC nAbs in nearly 60% and spike-specific CD8+ T cells in >80% of myeloma patients. Patients who develop breakthrough infections following vaccination have low levels of live-virus nAb.This article is highlighted in the In This Issue feature, p. 101

Kratom, a plant that produces opioid-like effects, has gained popularity in the U.S. for self-treating symptoms of chronic pain, mood disorders, and substance-use disorders (SUDs). Most data on kratom are from surveys into which current kratom-using adults could self-select; such surveys may underrepresent people who have used kratom and chosen to stop. Available data also do not adequately assess important psychosocial factors surrounding kratom use. In this study, U.S. adults who reported past 6-month alcohol, opioid, and/or stimulant use (N = 1,670) were recruited via Amazon Mechanical Turk between September and December 2020. Of the 1,510 evaluable respondents, 202 (13.4%) reported lifetime kratom use. Kratom-using adults, relative to others, were typically younger, male, unpartnered, without children, and had lower income. They had higher rates of chronic pain (31.7% vs. 21.9%, p = .003), childhood adversity, anxiety, and depression (p < .001), and lower perceived social rank (d = .19, .02-.22) and socioeconomic status (d = .37 .16-.26). They also reported higher use rates for most substances (except alcohol); this included medically supervised and unsupervised use of prescription opioids and diverted opioid agonist therapy (OAT) medications. Most (83.2%) met diagnostic criteria for any past-year SUD. Those reporting kratom use were less likely to reside in an urban/suburban area. The strongest predictors of kratom use were use of other drugs: cannabidiol (OR = 3.73), psychedelics (OR = 3.39), and nonmedical prescription opioids (OR = 1.72). Another strong predictor was lifetime OAT utilization (OR = 2.31). Despite seemingly poorer psychosocial functioning and health among respondents reporting lifetime kratom use, use of other substances may be the strongest indicators of kratom use. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Detection of insertions and deletions (InDels) by short-read next-generation sequencing (NGS) technology can be challenging because of frequent misaligned reads. A systematic analysis of short InDels (1 to 30 bases) and fms-related receptor tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs; 6 to 183 bases) from 46 clinical cases of solid or hematologic malignancy processed with a clinical NGS assay identified misaligned reads in every case, ranging from 3% to 100% of reads with the InDel showing mismapped bases. Mismaps also increased with InDel size. As a consequence, the clinical NGS bioinformatics pipeline undercalled the variant allele frequency by 1% to 84%, incorrectly called simultaneous single-base substitutions along with InDels, or did not report an FLT3 ITD that had been detected by capillary electrophoresis. To improve the ability of the pipeline to better detect and quantify InDels, we utilized a software program called Assembly-Based ReAligner (ABRA2) to more accurately remap reads. ABRA2 was able to correct 41% to 100% of the reads with mismapped bases and led to absolute increases in the variant allele frequency from 1% to 61% along with correction of all of the single-base substitutions except for two cases. ABRA2 could also detect multiple FLT3 ITD clones except for one 183-base ITD. Our analysis has found that ABRA2 performs well on short InDels as well as FLT3 ITDs that are100 bases.

Rifampicin, a potent enzyme inducer, causes marked reduction of dolutegravir exposure. Rifabutin, a less potent enzyme inducer, may offer an alternative to rifampicin. We aimed to characterize the population pharmacokinetics of dolutegravir when co-administered with rifabutin. We extended an existing dolutegravir model to include data from volunteers co-administered with dolutegravir 50 mg and rifabutin 300 mg once daily. We ran simulations of dolutegravir with and without rifabutin co-administration and compare dolutegravir trough concentrations with the IC

Most people’s private lives can be monitored by smartphone applications (apps). Apps have the potential to invade private spaces, access and map social interactions, track users’ whereabouts, and track their online activities. Our interest is in the volume of data that a specific app can and seeks to retrieve on a smartphone. Smartphone app privacy friendliness is normally evaluated based on single-source analyses, which often do not offer a thorough assessment of the app’s actual privacy threats. In order to analyze Android apps’ privacy, this study proposes a multi-source methodology. Our data sets and methodology from app manifestos, privacy policies, vulnerability analysis and user reviews were described. Results from a case study on ten well-known finance applications operating in Nigeria were provided in order to assess our methodology. Our findings showed distinct patterns regarding the possible privacy implications of apps, with some of the apps in the data set infringing fundamental privacy principles. The case study’s findings reveal significant differences that can guide users in making relevant app choices.

Sleep impairment is a common comorbid and debilitating symptom for persons with opioid use disorder (OUD). Research into underlying mechanisms and efficacious treatment interventions for OUD-related sleep problems requires both precise and physiologic measurements of sleep-related outcomes and impairment. This pilot examined the feasibility of a wireless sleep electroencephalography (EEG) monitor (Sleep Profiler™) to measure sleep outcomes and architecture among participants undergoing supervised opioid withdrawal. Sleep outcomes were compared to a self-reported sleep diary and opioid withdrawal ratings. Participants (n = 8, 100% male) wore the wireless EEG 85.6% of scheduled nights. Wireless EEG detected measures of sleep architecture including changes in total, NREM and REM sleep time during study phases, whereas the diary detected changes in wakefulness only. Direct comparisons of five overlapping outcomes revealed lower sleep efficiency and sleep onset latency and higher awakenings and time spent awake from the wireless EEG versus sleep diary. Associations were evident between wireless EEG and increased withdrawal severity, lower sleep efficiency, less time in REM and non-REM stages 1 and 2, and more hydroxyzine treatment; sleep diary was associated with total sleep time and withdrawal only. Data provide initial evidence that a wireless EEG is a feasible and useful tool for objective monitoring of sleep in persons experiencing acute opioid withdrawal. Data are limited by the small and exclusively male sample, but provide a foundation for using wireless EEG sleep monitors for objective evaluation of sleep-related impairment in persons with OUD in support of mechanistic and treatment intervention research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PURPOSE To examine COVID-19 mRNA vaccine–induced binding and neutralizing antibody responses in patients with non–small-cell lung cancer (NSCLC) to SARS-CoV-2 614D (wild type [WT]) strain and variants of concern after the primary 2-dose and booster vaccination. METHODS Eighty-two patients with NSCLC and 53 healthy volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2–specific binding and neutralizing antibody responses were evaluated by Meso Scale Discovery assay and live virus Focus Reduction Neutralization Assay, respectively. RESULTS A majority of patients with NSCLC generated binding and neutralizing antibody titers comparable with the healthy vaccinees after mRNA vaccination, but a subset of patients with NSCLC (25%) made poor responses, resulting in overall lower (six- to seven-fold) titers compared with the healthy cohort ( P = < .0001). Although patients age > 70 years had lower immunoglobulin G titers ( P = < .01), patients receiving programmed death-1 monotherapy, chemotherapy, or a combination of both did not have a significant impact on the antibody response. Neutralizing antibody titers to the B.1.617.2 (Delta), B.1.351 (Beta), and in particular, B.1.1.529 (Omicron) variants were significantly lower ( P = < .0001) compared with the 614D (WT) strain. Booster vaccination led to a significant increase ( P = .0001) in the binding and neutralizing antibody titers to the WT and Omicron variant. However, 2-4 months after the booster, we observed a five- to seven-fold decrease in neutralizing titers to WT and Omicron viruses. CONCLUSION A subset of patients with NSCLC responded poorly to the SARS-CoV-2 mRNA vaccination and had low neutralizing antibodies to the B.1.1.529 Omicron variant. Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant.

The availability of raw DNA and genetic interpretation tools allow individuals to access genetic health risk information, where analytical false-positives exist. Little is known about the experience of individuals who receive pathogenic or likely pathogenic variant(s) through raw DNA interpretation and follow-up with clinical confirmatory genetic testing. This qualitative study set out to describe the experiences of individuals who pursued clinical confirmatory genetic testing, including their perception of the process. Participants were recruited from social media and eligible if they discovered a potential pathogenic or likely pathogenic variant in a raw DNA interpretation report, completed clinical confirmatory genetic testing in the U.S., and provided documentation of those results. Individuals participated in semi-structured interviews, which were transcribed and inductively coded to identify themes. Of the 12 participants, 3 received clinical genetic testing results that confirmed pathogenic or likely pathogenic variants noted in raw DNA interpretation reports (confirmation positive), and 9 were not confirmed. Nearly all (n = 11) participants described emotional distress and information-seeking behavior as a coping mechanism after discovering a pathogenic or likely pathogenic variant in raw DNA interpretation. When pursuing confirmatory genetic testing, many (n = 9) faced challenges with finding knowledgeable healthcare providers and obtaining insurance coverage. Despite reporting concerns over raw DNA interpretation and a desire for more safeguards, almost all (n = 10) participants stated interest in using the service again. Overall, participants' experiences reveal they find personal utility in raw DNA interpretation results and provide insight into opportunities for patient and provider education.The availability of raw DNA data and online genetic interpretation tools allow individuals to access genetic health risk information, where false-positive results exist. Little is known about the experience of individuals who discover disease-causing variant(s) through raw DNA interpretation and follow-up with medical-grade confirmatory genetic testing. This qualitative study describes the experiences of individuals who pursued medical-grade confirmatory genetic testing in the U.S. after they discovered a potential disease-causing variant in a raw DNA interpretation report. Individuals participated in semi-structured interviews, which were transcribed and inductively coded to identify themes. Of the 12 participants, 3 received medical-grade genetic testing results that confirmed disease-causing variants noted in raw DNA interpretation reports, and 9 were not confirmed. Nearly all participants described emotional distress and information-seeking behavior after discovering a disease-causing variant in raw DNA interpretation. When pursuing confirmatory genetic testing, many faced challenges with finding knowledgeable healthcare providers and obtaining insurance coverage. Despite reporting concerns over raw DNA interpretation and a desire for more safeguards, almost all participants stated interest in using the service again. Overall, participants’ experiences reveal they find personal utility in raw DNA interpretation results and provide insight into opportunities for patient and provider education.

INTRODUCTION: Since 2007, kratom use in the United States has increased, centered around nonmedical self-treatment of pain, psychiatric, and substance use disorder (SUD) symptoms. Reports of kratom withdrawal have emerged amidst description of therapeutic effects, yet we know little about disordered use. Our objective was to assess DSM-5 SUD for kratom (“kratom use disorder”, KUD) and examine kratom withdrawal symptoms among those who ever used regularly. We also sought to identify clinical characteristics of respondents who qualified for current, remitted, or never KUD. METHODS: Between April-May 2021, we re-recruited online respondents who reported lifetime kratom use on an unrelated survey into our cross-sectional kratom survey study, permitting a diverse sample of current and former kratom-using persons. RESULTS: A total of 129/289 (44.6%) evaluable surveys were obtained. Over half (52.7%) of respondents never met KUD diagnostic criteria; 17.8% were assessed remitted, and 29.5% met current (past-year) KUD threshold. For past-year KUD, severity was: 14.0% mild, 7.0% moderate, and 8.5% severe. Pain, psychiatric symptoms, and polydrug use were found across all groups. KUD symptoms reflected increased use, tolerance, withdrawal, unsuccessful quit attempts, and craving; 9.3% reported decreases in important social, occupational, or recreational activities because of use. Withdrawal symptoms were moderate and included gastrointestinal upset, restlessness, anxiety, irritability, fatigue/low energy, and craving. CONCLUSIONS: As assessed here, tolerance and withdrawal are primary KUD features rather than psychosocial impairments. As kratom is often used among persons with a myriad of health conditions, clinicians should be aware of and assess for kratom use and withdrawal.

Carrying a handgun is an established risk factor for firearm violence, with detrimental and too often irreversible consequences for adolescents including injury and mortality. Although researchers identified a number of risk factors for adolescent handgun carriage, little is known regarding the role of strengths or developmental assets in buffering against risk. The goal of this study was to identify both risk and protective factors for handgun carriage among a predominantly African American (88%) community-based sample of adolescents ( Mage = 14.3) who resided in urban communities with high rates of poverty and exposure to violence. Consistent with prior work, we found that adolescents with access to a handgun or with friends who had carried a handgun had higher odds of carrying a handgun themselves in the past 3 months. Handgun access, friends’ handgun carriage, and beliefs supporting reactive aggression were identified as risk factors for handgun carriage. Although personal and social assets and positive outlook moderated these relations, the direction was contrary to our hypotheses. We believe that these findings are in part due to structural inequities and social norms impacting adolescents in urban communities characterized by concentrated poverty and high rates of violence. Our findings highlight the value of moving beyond a deficit-oriented framework to gain a more nuanced understanding of the dynamics among both positive and negative factors that alter risk for handgun carriage among African American youth living in low-income urban areas.

The mediodorsal thalamus is a multimodal region involved in a variety of cognitive behaviors, including olfactory attention, odor discrimination, and the hedonic perception of flavors. Although the mediodorsal thalamus forms connections with principal regions of the olfactory and gustatory networks, its role in processing olfactory and gustatory signals originating from the mouth remains unclear. Here, we recorded single-unit activity in the mediodorsal thalamus of behaving female rats during the intraoral delivery of individual odors, individual tastes, and odor-taste mixtures. Our results are the first to demonstrate that neurons in the mediodorsal thalamus dynamically encode chemosensory signals originating from the mouth. This chemoselective population is broadly tuned, exhibits excited and suppressed responses, and responds to odor-taste mixtures differently than an odor or taste alone. Furthermore, a subset of chemoselective neurons encodes the palatability-related features of tastes and may represent associations between previously experienced odor-taste pairs. Our results further demonstrate the multidimensionality of the mediodorsal thalamus and provide additional evidence of its involvement in processing chemosensory information important for ingestive behaviors.SIGNIFICANCE STATEMENTThe perception of food relies on the concurrent processing of olfactory and gustatory signals originating from the mouth. The mediodorsal thalamus is a higher-order thalamic nucleus involved in a variety of chemosensory-dependent behaviors and connects the olfactory and gustatory cortices with the prefrontal cortex. However, it is unknown how neurons in the mediodorsal thalamus process intraoral chemosensory signals. Using tetrode recordings in alert rats, our results are the first to show that neurons in the mediodorsal thalamus dynamically represent olfactory and gustatory signals from the mouth. Our findings are consistent with the mediodorsal thalamus being a key node between sensory and prefrontal cortical areas for processing chemosensory information underlying ingestive behavior.