The Cellular and Molecular Basis of Sour Taste.

Sour taste, the taste of acids, is one of the most enigmatic of the five basic taste qualities; its function is unclear and its receptor was until recently unknown. Sour tastes are transduced in taste buds on the tongue and palate epithelium by a subset of taste receptor cells, known as type III cells. Type III cells express a number of unique markers, which allow for their identification and manipulation. These cells respond to acid stimuli with action potentials and release neurotransmitters onto afferent nerve fibers, with cell bodies in geniculate and petrosal ganglia. Here, we review classical studies of sour taste leading up to the identification of the sour receptor as the proton channel OTOP1.

Requirement for an Otopetrin-like protein for acid taste in Drosophila.

Receptors for bitter, sugar, and other tastes have been identified in the fruit fly Drosophila melanogaster, while a broadly tuned receptor for the taste of acid has been elusive. Previous work showed that such a receptor was unlikely to be encoded by a gene within one of the two major families of taste receptors in Drosophila, the "gustatory receptors" and "ionotropic receptors." Here, to identify the acid taste receptor, we tested the contributions of genes encoding proteins distantly related to the mammalian Otopertrin1 (OTOP1) proton channel that functions as a sour receptor in mice. RNA interference (RNAi) knockdown or mutation by CRISPR/Cas9 of one of the genes, Otopetrin-Like A (OtopLA), but not of the others (OtopLB or OtopLC) severely impaired the behavioral rejection to a sweet solution laced with high levels of HCl or carboxylic acids and greatly reduced acid-induced action potentials measured from taste hairs. An isoform of OtopLA that we isolated from the proboscis was sufficient to restore behavioral sensitivity and acid-induced action potential firing in OtopLA mutant flies. At lower concentrations, HCl was attractive to the flies, and this attraction was abolished in the OtopLA mutant. Cell type-specific rescue experiments showed that OtopLA functions in distinct subsets of gustatory receptor neurons for repulsion and attraction to high and low levels of protons, respectively. This work highlights a functional conservation of a sensory receptor in flies and mammals and shows that the same receptor can function in both appetitive and repulsive behaviors.

How Risky is Online Sexting by Minors?

What proportion of minors who engage in sexting find themselves involved in an episode of image abuse? The data come from a US nationally representative sample of 2639 respondents aged 18-28 reporting about experiences before the age of 18, of whom 23% had engaged in sexting as minors. Among those who sexted the rate of image abuse was 37%, a risk ratio of 13.2 compared to those who did not engage in sexting. For females who sexted the victimization rate was particularly high, but sexting increased risk for females and males. Among the minors who only sexted occasionally (vs those who sexted frequently) the rate of abuse was still high (35%) and the reduction in risk modest. When we controlled for other background and demographic risk factors like adversities and prior sexual abuse, it did not substantially reduce the large risk entailed with sexting. Various harm reduction strategies may be needed to supplement messages about dangers and risks.

Ten simple rules to host an inclusive conference.

Conferences are spaces to meet and network within and across academic and technical fields, learn about new advances, and share our work. They can help define career paths and create long-lasting collaborations and opportunities. However, these opportunities are not equal for all. This article introduces 10 simple rules to host an inclusive conference based on the authors' recent experience organizing the 2021 edition of the useR! statistical computing conference, which attracted a broad range of participants from academia, industry, government, and the nonprofit sector. Coming from different backgrounds, career stages, and even continents, we embraced the challenge of organizing a high-quality virtual conference in the context of the Coronavirus Disease 2019 (COVID-19) pandemic and making it a kind, inclusive, and accessible experience for as many people as possible. The rules result from our lessons learned before, during, and after the organization of the conference. They have been written mainly for potential organizers and selection committees of conferences and contain multiple practical tips to help a variety of events become more accessible and inclusive. We see this as a starting point for conversations and efforts towards building more inclusive conferences across the world. * Translated versions of the English abstract and the list of rules are available in 10 languages in S1 Text: Arabic, French, German, Italian, Japanese, Korean, Portuguese, Spanish, Tamil, and Thai.

Growth Factor Signaling Regulates Mechanical Nociception in Flies and Vertebrates.

Mechanical sensitization is one of the most difficult clinical pain problems to treat. However, the molecular and genetic bases of mechanical nociception are unclear. Here we develop a Drosophila model of mechanical nociception to investigate the ion channels and signaling pathways that regulate mechanical nociception. We fabricated von Frey filaments that span the subthreshold to high noxious range for Drosophila larvae. Using these, we discovered that pressure (force/area), rather than force per se, is the main determinant of aversive rolling responses to noxious mechanical stimuli. We demonstrated that the RTK PDGF/VEGF receptor (Pvr) and its ligands (Pvfs 2 and 3) are required for mechanical nociception and normal dendritic branching. Pvr is expressed and functions in class IV sensory neurons, whereas Pvf2 and Pvf3 are produced by multiple tissues. Constitutive overexpression of Pvr and its ligands or inducible overexpression of Pvr led to mechanical hypersensitivity that could be partially separated from morphological effects. Genetic analyses revealed that the Piezo and Pain ion channels are required for mechanical hypersensitivity observed upon ectopic activation of Pvr signaling. PDGF, but not VEGF, peptides caused mechanical hypersensitivity in rats. Pharmacological inhibition of VEGF receptor Type 2 (VEGFR-2) signaling attenuated mechanical nociception in rats, suggesting a conserved role for PDGF and VEGFR-2 signaling in regulating mechanical nociception. VEGFR-2 inhibition also attenuated morphine analgesic tolerance in rats. Our results reveal that a conserved RTK signaling pathway regulates baseline mechanical nociception in flies and rats.SIGNIFICANCE STATEMENT Hypersensitivity to touch is poorly understood and extremely difficult to treat. Using a refined Drosophila model of mechanical nociception, we discovered a conserved VEGF-related receptor tyrosine kinase signaling pathway that regulates mechanical nociception in flies. Importantly, pharmacological inhibition of VEGF receptor Type 2 signaling in rats causes analgesia and blocks opioid tolerance. We have thus established a robust, genetically tractable system for the rapid identification and functional analysis of conserved genes underlying mechanical pain sensitivity.

Exposure to Multiple Forms of Bias Victimization on Youth and Young Adults: Relationships with Trauma Symptomatology and Social Support.

Research has documented that a significant portion of youth are exposed to bias victimization. However, less is known about whether experiencing certain types of bias victimization (e.g., sexual orientation bias) is more or less likely to be related to a more extensive bias victimization history (i.e., experiencing multiple types of bias victimization) and whether exposure to multiple types of bias victimization explains any relationships between specific types of bias victimization and negative outcomes. To address these gaps, the current study explores relationships between exposure to multiple types of bias-motivated victimization, trauma symptomatology and perceived social support. Participants were 854 youth and young adults (60.9% female) from three higher risk communities who completed a survey on personal experiences with bias-related victimization. The average age of participants was 16.6 years; 28.5% of the sample described themselves as Black or African American; 13.4% as Hispanic or Latino (any race); 45.3% as White, and 12.8% as another race. Sixty-nine percent of the sample described their sexual orientation as heterosexual; 8.9% as gay, lesbian, or homosexual; 12.5% as bisexual; and 9.5% as another sexual orientation. Sixty-three percent of participants reported at least one type of bias victimization in their lifetime, and more than one in three youth (38.7%) experienced two or more types of bias victimization in their lifetimes (18.1% two types, 12.1% three types, and 8.5% four or more types). Experiencing multiple types of bias victimization was related to higher trauma symptomatology and less perceived social support. Experiencing multiple types of bias victimization attenuated or eliminated the association between individual types of bias victimization and well-being. The findings contribute to a growing body of research demonstrating the damaging mental health effects of occupying multiple marginalized statuses, and points to the cumulation of bias victimization experiences as an important factor contributing to significant differences in well-being and support among youth and young adults.

Peer Victimization Patterns and Trauma Symptoms in a National Longitudinal Sample of Youth.

Using a nationally representative sample of 791 youth, ages 8-17 at baseline, this study identified patterns over a 2-year period in specific forms of peer victimization and examined differences in the mental health consequences of those patterns. Findings show that, among the victimized, physical assault had relatively high persistence compared to other forms, while physical intimidation and emotional bullying had relatively high rates of desistence. Emotional bullying at T1 was associated with increased risk of T2 Internet harassment and Internet harassment at T1 strongly predicted T2 dating violence. Patterns of victimization over time differed in their relationship with trauma symptoms. Findings emphasized the importance of recency and the distress of new victimization experiences, rather than the chronicity or repetition of victimization. Understanding variations in peer victimization patterns and outcomes over time can help to inform interventions that better target sources of risk across adolescence.

The Youth Firearm Risk and Safety Tool (Youth-FiRST): Psychometrics and Validation of a Gun Attitudes and Violence Exposure Assessment Tool.

This study reports on the development of a comprehensive assessment of exposure to guns and gun-related violence for evaluating the risk of gun-related trauma. Gun access, gun attitudes, gun safety education, and exposure to gun violence were measured. Participants were 630 youth, aged 2-17. Youth, ages 10-17, completed a self-report survey and caregivers of young children, ages 2-9, completed the survey as a proxy for that child. The youth were from urban (n = 286) and rural (n = 344) areas. Factor analysis, item response theory, and structural equation modeling were used. Two factors described access to guns, two factors described gun attitudes, and a single construct captured gun safety education. The gun violence exposure factor showed strong associations with trauma symptomatology. The individual constructs showed good psychometric properties and measurement noninvariance by urbanicity.

Gun Violence Exposure and Posttraumatic Symptoms Among Children and Youth.

Although statistics on youth homicide and injury from gun violence are available, little research has focused on how gun violence overlaps with other victimizations or on the psychological impact of gun violence on children. Pilot survey data were collected on the experiences of 630 U.S. children (age range: 2-17 years) from Boston, Philadelphia, and rural areas of eastern Tennessee. Youth aged 10-17 years completed a self-report survey on a wide range of gun violence exposures, and parents of younger children (aged 2-9 years) completed the survey as a proxy for that child. Direct gun violence exposure, witnessing gun violence, and hearing gunshots were all significantly associated with other forms of victimization, rs = .10-.38, p < .001. The findings suggest that youth who experience direct gun violence are often exposed to multiple violent contexts. For older youth (ages 10-17 years) polyvictimization was most strongly associated with posttraumatic symptoms, ß = .35, p < .001, although witnessing gun violence still uniquely predicted a higher level of symptoms, ß = .18, p < .01. For younger children (ages 2-9 years), hearing and witnessing gun violence were both related to posttraumatic symptoms, ß = .15, p < .01 for both, even after controlling for polyvictimization. Mental health professionals and trauma-informed services should be mindful that the traumatic impact of gun violence for children may not necessarily be attached to direct victimization experiences but may also result from simply seeing or hearing it in their neighborhoods.

Disability weights for infectious diseases in four European countries: comparison between countries and across respondent characteristics.

Background: In 2015, new disability weights (DWs) for infectious diseases were constructed based on data from four European countries. In this paper, we evaluated if country, age, sex, disease experience status, income and educational levels have an impact on these DWs. Methods: We analyzed paired comparison responses of the European DW study by participants' characteristics with separate probit regression models. To evaluate the effect of participants' characteristics, we performed correlation analyses between countries and within country by respondent characteristics and constructed seven probit regression models, including a null model and six models containing participants' characteristics. We compared these seven models using Akaike Information Criterion (AIC). Results: According to AIC, the probit model including country as covariate was the best model. We found a lower correlation of the probit coefficients between countries and income levels (range rs: 0.97-0.99, P < 0.01) than between age groups (range rs: 0.98-0.99, P < 0.01), educational level (range rs: 0.98-0.99, P < 0.01), sex (rs = 0.99, P < 0.01) and disease status (rs = 0.99, P < 0.01). Within country the lowest correlations of the probit coefficients were between low and high income level (range rs = 0.89-0.94, P < 0.01). Conclusions: We observed variations in health valuation across countries and within country between income levels. These observations should be further explored in a systematic way, also in non-European countries. We recommend future researches studying the effect of other characteristics of respondents on health assessment.

Characteristics of bias-based harassment incidents reported by a national sample of U.S. adolescents.

Using a national sample of youth from the U.S., this paper examines incidents of bias-based harassment by peers that include language about victims' perceived sexual orientation, race/ethnicity, religion, weight or height, or intelligence. Telephone interviews were conducted with youth who were 10-20 years old (n = 791). One in six youth (17%) reported at least one experience with bias-based harassment in the past year. Bias language was a part of over half (52%) of all harassment incidents experienced by youth. Perpetrators of bias-based harassment were similar demographically to perpetrators of non-biased harassment. However, bias-based incidents were more likely to involve multiple perpetrators, longer timeframes and multiple harassment episodes. Even controlling for these related characteristics, the use of bias language in incidents of peer harassment resulted in significantly greater odds that youth felt sad as a result of the victimization, skipped school, avoided school activities, and lost friends, compared to non-biased harassment incidents.

Exposure to Medication Overdose as an Adversity in Childhood.

PURPOSE: To determine the prevalence of youth exposure to medication or pill overdose by someone close to them, as well as how common this is within the spectrum of major stressful events and child victimization experienced by youth. DESIGN AND METHODS: Data were collected as part of the Third National Survey of Children's Exposure to Violence, a nationally representative telephone survey of youth, ages 2-17years (N=3738) conducted in 2013. The analytical subset for the current paper is youth ages 10-17years (n=1959). RESULTS: Estimates indicate that approximately 1 in 12 youth (8%), ages 10-17 have been exposed to medication overdose by someone close to them in their lifetimes. Overdose exposure is related to recent trauma symptoms, alcohol and other substance use. However, these relationships appear to be largely driven by the co-existence of major stressful events these youth are experiencing. Alcohol use is the exception; exposure to medication overdose continues to be related to past year personal alcohol use even after adjusting for other lifetime stressful events. CONCLUSIONS: Having a close family member or friend overdose on a medication is a common experience among U.S. youth and related to high rates of co-occurring stressful events. PRACTICE IMPLICATIONS: Health care providers should be aware that youth exposure to medication overdoses likely indicates exposure to other recognized adversities. Youth with a caregiver who has had an overdose may require an urgent response including referral to crisis intervention through child and family services.

Safety of Computed Tomographic Angiography in the Evaluation of Patients With Acute Stroke: A Single-Center Experience.

BACKGROUND AND PURPOSE: Noncontrasted head computed tomography (NCHCT) has long been the standard of care for acute stroke imaging. New guidelines recommending advanced vascular imaging to identify eligible patients for endovascular therapy have renewed safety concerns on the use of contrast in the emergent setting without laboratory confirmation of renal function. METHODS: We compared computed tomographic angiography (CTA) versus NCHCT alone during acute stroke evaluation with focus on renal safety and timeliness of therapy delivery. We reviewed data on all emergency department patients for whom the Acute Stroke Intervention Team was activated between December 2013 and September 2014. Primary outcomes included acute kidney injury and change in serum creatinine from presentation to 24 to 48 hours (Δ serum creatinine [Cr]). We assessed therapy delay using door-to-CT and door-to-needle times. RESULTS: Of 289 patients requiring Acute Stroke Intervention Team activation, 157 received CTA and 132 NCHCT only. There was no difference between groups in mean Cr at 24 to 48 hours (1.06 CTA; 1.40 NCHCT; P=0.059), ΔCr (-0.07 CTA, -0.11 NCHCT, P=0.489), or rates of acute kidney injury (5 CTA, 7 NCHCT, P=0.422). There was no significant difference in mean intravenous tissue plasminogen activator treatment times (68.11 minutes CTA, 81.36 minutes NCHCT; P=0.577). In the 157 patients who underwent CTA, 16 (10.2%) vascular anomalies and 55 (35.0%) high-grade stenoses or occlusions were identified. CONCLUSIONS: CTA acquisition during acute stroke evaluation was safe with regards to renal function and did not delay appropriate therapy delivery. Acute CTA acquisition offers additional clinical value in rapid identification of vascular abnormalities.

Poly-victimization and resilience portfolios: Trends in violence research that can enhance the understanding and prevention of elder abuse.

This literature review assesses the current state of knowledge about elder abuse and mistreatment, focusing on the lack of incorporation of all forms of elder victimization and the benefits of a poly-victimization framework. This review also includes existing knowledge on risk factors and calls for a greater focus on protective factors and a greater inclusion on family and community factors. Future research, prevention, and intervention would benefit from considering the true burden of elder victimization and a greater implementation of strengths-based approaches to programs.

Can child injury prevention include healthy risk promotion?

To reflect on the role of risk-taking and risky play in child development and consider recommendations for the injury prevention field, a symposium was held prior to the November 2013 Canadian Injury Prevention and Safety Promotion Conference. Delegates heard from Canadian and international researchers, practitioners and play safety experts on child development, play space design and playground safety, provision of recreation, and legal and societal perceptions of risk and hazard. The presenters provided multidisciplinary evidence and perspectives indicating the potential negative effect on children's development of approaches to injury prevention that prioritise safety and limit children's opportunities for risky play. Delegates considered the state of the field of injury prevention and whether alternative approaches were warranted. Each presenter prepared a discussion paper to provide the opportunity for dialogue beyond attendees at the symposium. The resulting discussion papers provide a unique opportunity to consider and learn from multiple perspectives in order to develop a path forward.

Victim Reports of Bystander Reactions to In-Person and Online Peer Harassment: A National Survey of Adolescents.

Bullying prevention is increasingly targeting education to bystanders, but more information is needed on the complexities of bystander actions across a wide variety of incidents, including both online and in-person peer harassment. The current study analyzes victim report data from a nationally representative survey of youth ages 10-20 (n = 791; 51% female). Bystander presence was common across all harassment incident types (80% of incidents). In contrast to previous research, our study found that supportive bystander behaviors occurred at relatively high rates. Unfortunately, antagonistic bystander behaviors, although less common, were predictive of higher negative impact for the victim. A large percentage of victims (76%) also disclosed the harassment to confidants, who play an important role as secondary bystanders. While friends were the most common confidant, incidents were also disclosed to adults at high rates (60%) and with mostly positive results. The findings suggest that prevention programs could increase their impact by targeting education to both direct witnesses and confidants, and considering a wider variety of peer victimization incident types.

The prevalence of child sexual abuse with online sexual abuse added.

BACKGROUND AND OBJECTIVE: Research efforts are measuring various forms of online sexual abuse. There is a need to incorporate such measures of online sexual abuse into the calculation of overall prevalence rates for child sexual abuse. PARTICIPANTS: A sample of 2639 respondents aged 18-to-28 was recruited from a nationally representative online panel. METHODS: Using an online questionnaire, respondents were assessed via self-report about 9 types of online sexual abuse in childhood and were also assessed with 2 questions that have been used to assess generic child sexual abuse prevalence in previous surveys. RESULTS: The addition of the online abuse to the generic questions about child sexual abuse raised the overall prevalence rate from 13.5 % to 21.7 %. The rate for females increased from 19.8 % to 31.6 % and for males from 6.2 % to 10.8 %. The largest independent contribution to the overall combined increase were the offenses involving non-consensual image sharing and voluntary online sexual interactions with an impermissibly older adult partner. The inclusion of the online sexual abuse exposures also increased the ability to identify the survivors with the highest levels of current psychological distress. CONCLUSION: The study highlights the importance of counting and including online sexual abuse in efforts to estimate the overall prevalence of childhood sexual abuse. The paper proposes 2 or 3 questions that could be added to sexual abuse questionnaires to assess these online offenses efficiently.

Prevalence of Technology-Facilitated Abuse Among Sexual and Gender Minority Youths.

Importance: Digital communication and imaging technologies have created new opportunities for technology-facilitated abuse (TFA) and necessitate a better understanding of how and why the risk for TFA varies across different groups of youths. Objectives: To compare the prevalence of TFA among youths across 5 different sexual and gender identity groups, and to identify risk factors that may explain variations in TFA risk. Design, Setting, and Participants: A US nationally representative online survey was conducted among 2639 young adults recruited from the KnowledgePanel online panel from November 19 to December 29, 2021. Individuals aged 18 to 28 years were asked retrospectively about TFA and a variety of other youth experiences in childhood (aged <18 years). Main Outcomes and Measures: Participants were asked about their sexual and gender identities, 11 types of TFA occurring before the age of 18 years, and several potential risk factors. Prevalence rates of any TFA were compared across sexual and gender identity groups, and analyses were conducted to identify risk factors that help explain group differences. Weights were developed to compensate for gender, education, race and ethnicity, household income, census region, and metropolitan status disproportions. Results: Among the 2510 respondents (mean [SD] age, 24.8 [2.8] years) who provided gender and sexual identity information, 46.5% (95% CI, 41.9%-51.1%) were cisgender heterosexual females, 25.2% (95% CI, 21.6%-29.1%) were cisgender sexual minority females, 18.3% (95% CI, 14.4%-22.9%) were cisgender heterosexual males, 6.8% (95% CI, 4.6%-9.9%) were cisgender sexual minority males, and 3.3% (95% CI, 2.0%-5.4%) were gender minority individuals. The prevalence of TFA occurring before the age of 18 years was highest among sexual minority females (55.3%; 95% CI, 48.0%-62.4%) and gender minority individuals (53.4%; 95% CI, 33.5%-72.2%). Rates of sexting were highest among cisgender sexual minority females (38.8%; 95% CI, 19.1%-58.8%) and gender minority individuals (36.7%; 95% CI, 19.1%-58.8%) and represented the strongest risk factor for TFA exposure (odds ratio, 5.7; 95% CI, 4.0-8.0). However, it explained little variation in TFA across groups once early in-person adversity, sexual abuse, bullying, and maltreatment were taken into account. Conclusions and Relevance: This study demonstrates the risk of TFA among sexual and gender minority youths and the need to target prevention efforts toward these vulnerable groups. In addition to strategies to reduce risky behavior, efforts to lower the risk of early sexual abuse, bullying, and maltreatment are likely to also be effective in decreasing TFA among these marginalized groups.

Characteristics and Dynamics of Cyberstalking Victimization Among Juveniles and Young Adults.

Using the nationally representative Ipsos online KnowledgePanel, the sample included three hundred thirty-six 18- to 28-year-olds who retrospectively reported first cyberstalking incidents as juveniles (9- to 17-year-olds) or adults. Half of the sample first experienced cyberstalking as juveniles and half first experienced it as adults. Juveniles were more likely to have more than two perpetrators in the same episode, to experience more violent threats, and to avoid people because of what happened. Few reported the incident to the police, with juveniles less likely to report it to the police. Cyberstalking of juveniles appears just as or more serious than cyberstalking of adults.

Contexts and Characteristics of Imaged-Based Sexual Exploitation and Abuse of Children: Incident Dynamics in a National Sample.

This paper describes incident characteristics and dynamics associated with six specific forms of image-based sexual exploitation and abuse of children (IBSEAC). Data were collected on a national sample of 2639 individuals aged 18-to-28 from a probability-based online panel. Respondents completed a self-administered survey questionnaire, providing detailed follow-up information on their experiences of image-based sexual victimization before the age of 18. A total of 607 incidents of IBSEAC were included in the analyses. Findings show substantial diversity in incident characteristics within and across the six forms of IBSEAC (nonconsensual sharing of sexual images, nonconsensual taking or making of images, forced image recruitment, threatened sharing, voluntary image sharing with an older adult, and commercial sexual exploitation involving images). Some notable patterns include frequent involvement of perpetrators who are other youth or young adults, who are known in-person to the victim, and who are intimate partners. The diversity and complexity of dynamics revealed in this study underscores the need for careful design and evaluation of prevention programs and the core messages directed at youth.