Constitutive sodium permeability in a C. elegans two-pore domain potassium channel.

Two-pore domain potassium (K2P) channels play a central role in modulating cellular excitability and neuronal function. The unique structure of the selectivity filter in K2P and other potassium channels determines their ability to allow the selective passage of potassium ions across cell membranes. The nematode C. elegans has one of the largest K2P families, with 47 subunit-coding genes. This remarkable expansion has been accompanied by the evolution of atypical selectivity filter sequences that diverge from the canonical TxGYG motif. Whether and how this sequence variation may impact the function of K2P channels has not been investigated so far. Here, we show that the UNC-58 K2P channel is constitutively permeable to sodium ions and that a cysteine residue in its selectivity filter is responsible for this atypical behavior. Indeed, by performing in vivo electrophysiological recordings and Ca2+ imaging experiments, we demonstrate that UNC-58 has a depolarizing effect in muscles and sensory neurons. Consistently, unc-58 gain-of-function mutants are hypercontracted, unlike the relaxed phenotype observed in hyperactive mutants of many neuromuscular K2P channels. Finally, by combining molecular dynamics simulations with functional studies in Xenopus laevis oocytes, we show that the atypical cysteine residue plays a key role in the unconventional sodium permeability of UNC-58. As predicting the consequences of selectivity filter sequence variations in silico remains a major challenge, our study illustrates how functional experiments are essential to determine the contribution of such unusual potassium channels to the electrical profile of excitable cells.

Testing a Brief Quitline Intervention for Tobacco Cannabis Co-Users: A Randomized Controlled Pilot Study.

Background: Tobacco cannabis co-use is common and becoming more prevalent. Frequent and heavy users of cannabis may struggle to quit smoking. Quitlines offer free cessation treatment in the United States and 25% of quitline callers may also be cannabis users. The present paper describes a randomized pilot study of a tailored intervention for cannabis and cigarette co-users. The intervention combines the quitline smoking cessation treatment with a motivational enhancement therapy-based cannabis intervention. Methods: The randomized pilot study was conducted within four state-funded quitlines with quitline coaches as interventionists. 102 quitline callers who were cannabis and cigarette co-users were randomized to receive treatment as usual (TAU) or the new Quitline Check-Up (QLCU) intervention. Outcomes were collected 90 days post-randomization. Primary outcomes included feasibility and acceptability of delivering the QLCU in the quitline setting. Secondary outcomes included 7-day point prevalence tobacco abstinence, past 30-day cannabis use, and Cannabis Use Disorder Identification Test scores. Results: Study participants were heavy cannabis users, averaging 25 days of use in the past 30; nearly 70% used at a level considered hazardous. Fidelity ratings indicated coaches were successful at delivering the intervention. Treatment engagement was high for both groups (TAU m = 3.4 calls; QLCU m = 3.6 calls) as was treatment satisfaction. Intent-to-treat quit rates (with survey non-responders classified as smokers) were 28.6% for the TAU control group and 24.5% for the QLCU group (P = .45). Discussion: Hazardous cannabis use rates were high in this sample of tobacco cannabis co-users calling quitlines to quit smoking. The intervention for co-users was acceptable and feasible to deliver. No improvements in tobacco cessation outcomes were observed. Pragmatic intervention development within a real-world clinical setting can streamline the intervention development process. More research is needed on tobacco cannabis co-users and who can benefit from a tailored intervention. Registered: ClinicalTrials.gov NCT04737772, February 4, 2021.

Alcohol use disorder as a moderator of the relationship between posttraumatic stress disorder and suicidality among military personnel.

BACKGROUND: Alcohol use disorder (AUD), posttraumatic stress disorder (PTSD), and suicide are substantial public health concerns among military service members, yet the nature of their relationships is not well understood. Here, we tested the hypothesis that AUD moderates the relationship between PTSD symptom severity and suicidal ideation. METHODS: This secondary analysis uses data collected at baseline for a randomized clinical trial. The sample consists of 160 active-duty service members from three service branches (Army, Air Force, and Navy). All participants met diagnostic criteria for PTSD and were not engaged in evidence-based PTSD treatment at the time of enrollment. Zero-inflated Poisson generalized linear regression models were used to test the associations of PTSD and AUD symptom severity with the presence and severity of suicidal ideation. RESULTS: Findings suggest that AUD symptom severity moderates (i.e., amplifies) the relationship between PTSD symptoms and severity of suicidal ideation among military personnel with untreated PTSD. Among service members with mild or absent AUD, we found no significant association between PTSD symptoms and the severity of suicidal ideation. However, when AUD severity was average (i.e., sample mean) or high (mean + 1SD), PTSD symptoms were significantly positively associated with the severity of suicidal ideation. CONCLUSIONS: This study highlights the importance of assessing AUD and PTSD as a part of suicide risk evaluations of veterans. The results also provide strong support for the maintenance and further development in the military health system of treatment programs that simultaneously address AUD and PTSD comorbidity.

Improving voluntary engagement for posttraumatic stress disorder treatment among active-duty service members using motivational enhancement therapy.

OBJECTIVE: Posttraumatic stress disorder (PTSD) prevalence in the military is high and effective treatments are underutilized. Motivational enhancement therapy (MET) "check-ups" are brief interventions to elicit treatment uptake for those who are nontreatment seeking. The aim of the current study was to test the efficacy of a novel MET intervention designed to promote treatment engagement among active-duty U.S. military personnel with untreated PTSD. METHOD: One hundred and sixty-one active-duty service members who met the criteria for PTSD were randomized to MET or treatment as usual (TAU, treatment resource and referral). MET participants (n = 82) received up to three 30-90 min telephone sessions. TAU participants (n = 79) were mailed PTSD resources and referrals. Follow-up assessments were conducted 6-week, 3- and 6-month postbaseline. RESULTS: Mixed effect model results indicated treatment uptake significantly increased over time but there were no significant differences between conditions or interactions. PTSD symptom severity significantly decreased for both conditions. There was also a significant three-way interaction with baseline readiness-to-change confidence. Those low in baseline readiness-to-change saw more favorable effects of MET (relative to TAU) at 6-month follow-up. CONCLUSIONS: Results suggest both MET and high-quality referral options have promise as a means of increasing evidence-based treatment uptake and decreasing PTSD for service members with PTSD. MET may be particularly useful for individuals with low confidence in their ability to address PTSD. Given the individual and societal costs of PTSD, there is a need for interventions facilitating treatment uptake. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Scoping Review of Cannabis-Reduction Psychosocial Interventions and Reasons for Use among Young Adults with Psychosis.

Objective: No evidence-based intervention effectively reduces cannabis use in young adults with psychosis (YAP). To generate hypotheses about why, a scoping review was conducted to synthesize evidence about motivations for cannabis use and reduction/cessation for YAP and the psychosocial interventions trialed to identify possible gaps between motivations and interventive strategies. Methods: A systematic literature search was conducted in December, 2022. Reviews of titles and abstracts (N = 3,216) and full-texts (n = 136) resulted in 46 articles. Results: YAP use cannabis for pleasure, to reduce dysphoria, and for social and recreational reasons; motivations for cessation include insight about cannabis-psychosis interactions, incompatibility with goals and social roles, and support from social networks. Interventions with at least minimal evidence of efficacy include motivational interviewing, cognitive-behavioral strategies, and family skills training. Conclusions: Authors recommend additional research on mechanisms of change and motivational enhancement therapy, behavioral activation, and family-based skills interventions matched to YAP motivations for use/cessation.

Provider Intentions to Implement Cannabis Use Intervention in First Episode Psychosis Treatment.

Young adults with first episode psychosis use cannabis at high rates. In light of progressively tolerant attitudes toward cannabis, decreased perceptions of risk, and limited implementation of substance use modules within coordinated specialty care (CSC) programs, this study sought to describe factors contributing to CSC providers' intentions to implement motivational enhancement therapy (MET) for cannabis reduction. Two focus groups were conducted with CSC providers (n = 14), with questions guided by theory of planned behavior. Content and thematic analyses were conducted to identify salient themes associated with the theory. Participants generally indicated intentions to implement MET; limiting factors included concerns about clients' willingness to discuss cannabis use, perception of support for abstinence-only goals, and concerns about intervention mechanics such as computerized assessments. To reduce barriers limiting provider intention to implement MET, authors recommend training on assessment protocols, the merits of harm-reduction, and strategies for lower-risk cannabis use.Please confirm if the author names are presented accurately and in the correct sequence. Author 1 Given name: [Ryan] Last name [Petros]. Author 2 Given name: [Denise D.] Last name [Walker]. Author 3 Given name: [Adam] Last name [Davis]. Author 4 Given name: [Maria] Last name [Monroe-DeVita]. Also, kindly confirm the details in the metadata are correct.Confirmed!

Changes in lipid metabolism driven by steroid signalling modulate proteostasis in C. elegans.

Alzheimer's, Parkinson's and Huntington's diseases can be caused by mutations that enhance protein aggregation, but we still do not know enough about the molecular players of these pathways to develop treatments for these devastating diseases. Here, we screen for mutations that might enhance aggregation in Caenorhabditis elegans, to investigate the mechanisms that protect against dysregulated homeostasis. We report that the stomatin homologue UNC-1 activates neurohormonal signalling from the sulfotransferase SSU-1 in ASJ sensory/endocrine neurons. A putative hormone, produced in ASJ, targets the nuclear receptor NHR-1, which acts cell autonomously in the muscles to modulate polyglutamine repeat (polyQ) aggregation. A second nuclear receptor, DAF-12, functions oppositely to NHR-1 to maintain protein homeostasis. Transcriptomics analyses of unc-1 mutants revealed changes in the expression of genes involved in fat metabolism, suggesting that fat metabolism changes, controlled by neurohormonal signalling, contribute to protein homeostasis. Furthermore, the enzymes involved in the identified signalling pathway are potential targets for treating neurodegenerative diseases caused by disrupted protein homeostasis.

A Community Engaged Approach in Adapting Motivational Interviewing and Skills Training for Native Americans With Experiences of Substance Misuse.

OBJECTIVE: American Indian and Alaskan Natives (AIAN) are regenerating cultural knowledge and practices to adapt westernized evidence-based interventions to address health concerns such as substance use. This study describes the process of selecting, adapting, and implementing motivational interviewing plus cognitive behavior therapy (motivational interviewing + Skills Training; MIST) for use in a combined substance use intervention with a rural, Northwest tribal community. METHODS: An established community and academic partnership worked together to make culturally mindful changes to MIST. The partnership incorporated community leaders/Elders (n = 7), providers (n = 9), and participants (n = 50) to implement an iterative process of adapting and implementing the adapted form of MIST. RESULTS: Key adaptations included presenting concepts grounded in tribal values, providing examples from the community perspective, and incorporating cultural customs and traditions. Overall, the MIST adaptation was favorably received by participants, and the adaptation appeared feasible. CONCLUSIONS: Adapted MIST appeared to be an acceptable intervention for this Native American community. Future research should evaluate the interventions efficacy in reducing substance use among this and other Native American communities. Future clinical research should consider strategies outlined in this adaptation as a potential process for working with Native American communities to implement culturally appropriate interventions.

Social support and treatment utilization for posttraumatic stress disorder: Examining reciprocal relations among active duty service members.

Evidence-based treatments for posttraumatic stress disorder (PTSD) are underutilized by active duty service members in the United States. Social support may help service members overcome avoidance and facilitate treatment utilization. In turn, treatment utilization may improve social support. To evaluate these possibilities, the aim of the current study was to examine potential reciprocal associations between social support and treatment utilization among service members. Secondary analyses were conducted on a randomized controlled trial of 161 U.S. military service members with PTSD. Participants completed assessments of perceived social support and attendance at individual therapy sessions at baseline and 3- and 6-month follow-ups. To determine reciprocal relations between social support and treatment utilization, a Bayesian approach was used to estimate a random-intercept cross-lagged panel model with a two-part variable for treatment utilization (i.e., any therapy, and if so, dose). There were no between-person associations between average social support and treatment utilization. One prospective cross-lagged within-person association emerged as significant: social support at 3 months was negatively associated with any therapy use at 6 months; the model explained 26.1% of the variance in this observed variable. The findings revealed that low social support promoted subsequent treatment utilization, but such treatment did not lead to changes in social support. This suggests service members with PTSD may have been motivated to attend individual therapy in pursuit of social connection and support. Future research is needed to determine if reciprocal associations between various forms of social support and therapy utilization differ by treatment modality.

What's In It for Me? Motivating the Untreated Abuser to Consider Treatment.

This paper presents findings of a second trial evaluating telephone-based motivational enhancement therapy (MET) to motivate untreated and unadjudicated men who abuse their intimate partners to explore treatment options. Participants' perceptions of how their abuse is negatively affecting them personally are a highlight of the paper. One hundred forty-one adult men were recruited through social marketing and randomly assigned to the intervention (MET) or comparison (Mail) group. The MET condition consisted of two feedback sessions guided by a personalized feedback report on participants' intimate partner violence (IPV) and substance use. The Mail condition included a mailed educational brochure on IPV and substance use. Results supported the likely effectiveness of MET in short-term reduction of IPV behavior, marijuana use, and increasing motivation for treatment seeking particularly for participants who reported more adverse consequences of IPV to themselves. Findings emphasize the importance of including a focus in interventions on IPV's impact on the abusers themselves. The study's virtual participation and success in reaching and retaining a diverse population of male abusers can contribute to transformative justice and communities looking for alternative early interventions for men of color prior to encountering the criminal justice system.

The diverse functions of the DEG/ENaC family: linking genetic and physiological insights.

The DEG/ENaC family of ion channels was defined based on the sequence similarity between degenerins (DEG) from the nematode Caenorhabditis elegans and subunits of the mammalian epithelial sodium channel (ENaC), and also includes a diverse array of non-voltage-gated cation channels from across animal phyla, including the mammalian acid-sensing ion channels (ASICs) and Drosophila pickpockets. ENaCs and ASICs have wide ranging medical importance; for example, ENaCs play an important role in respiratory and renal function, and ASICs in ischaemia and inflammatory pain, as well as being implicated in memory and learning. Electrophysiological approaches, both in vitro and in vivo, have played an essential role in establishing the physiological properties of this diverse family, identifying an array of modulators and implicating them in an extensive range of cellular functions, including mechanosensation, acid sensation and synaptic modulation. Likewise, genetic studies in both invertebrates and vertebrates have played an important role in linking our understanding of channel properties to function at the cellular and whole animal/behavioural level. Drawing together genetic and physiological evidence is essential to furthering our understanding of the precise cellular roles of DEG/ENaC channels, with the diversity among family members allowing comparative physiological studies to dissect the molecular basis of these diverse functions.

Physiological insight into the conserved properties of Caenorhabditis elegans acid-sensing degenerin/epithelial sodium channels.

Acid-sensing ion channels (ASICs) are members of the diverse family of degenerin/epithelial sodium channels (DEG/ENaCs). They perform a wide range of physiological roles in healthy organisms, including in gut function and synaptic transmission, but also play important roles in disease, as acidosis is a hallmark of painful inflammatory and ischaemic conditions. We performed a screen for acid sensitivity on all 30 subunits of the Caenorhabditis elegans DEG/ENaC family using two-electrode voltage clamp in Xenopus oocytes. We found two groups of acid-sensitive DEG/ENaCs characterised by being either inhibited or activated by increasing proton concentrations. Three of these acid-sensitive C. elegans DEG/ENaCs were activated by acidic pH, making them functionally similar to the vertebrate ASICs. We also identified three new members of the acid-inhibited DEG/ENaC group, giving a total of seven additional acid-sensitive channels. We observed sensitivity to the anti-hypertensive drug amiloride as well as modulation by the trace element zinc. Acid-sensitive DEG/ENaCs were found to be expressed in both neurons and non-neuronal tissue, highlighting the likely functional diversity of these channels. Our findings provide a framework to exploit the C. elegans channels as models to study the function of these acid-sensing channels in vivo, as well as to study them as potential targets for anti-helminthic drugs. KEY POINTS: Acidosis plays many roles in healthy physiology, including synaptic transmission and gut function, but is also a key feature of inflammatory pain, ischaemia and many other conditions. Cells monitor acidosis of their surroundings via pH-sensing channels, including the acid-sensing ion channels (ASICs). These are members of the degenerin/epithelial sodium channel (DEG/ENaC) family, along with, as the name suggests, vertebrate ENaCs and degenerins of the roundworm Caenorhabditis elegans. By screening all 30 C. elegans DEG/ENaCs for pH dependence, we describe, for the first time, three acid-activated members, as well as three additional acid-inhibited channels. We surveyed both groups for sensitivity to amiloride and zinc; like their mammalian counterparts, their currents can be blocked, enhanced or unaffected by these modulators. Likewise, they exhibit diverse ion selectivity. Our findings underline the diversity of acid-sensitive DEG/ENaCs across species and provide a comparative resource for better understanding the molecular basis of their function.

Does Effectiveness of a Brief Substance Use Treatment Depend on PTSD? An Evaluation of Motivational Enhancement Therapy for Active-Duty Army Personnel.

OBJECTIVE: Posttraumatic stress disorder (PTSD) with comorbid substance use disorders (SUDs) has been associated with poorer treatment outcomes. The present study examined associations between provisional PTSD at baseline and 3 months with 6-month treatment outcomes from either a one-session motivational enhancement therapy (MET) or education intervention addressing substance use. METHOD: Secondary analyses were conducted on a randomized clinical trial comparing a novel MET intervention to an educational intervention for Army personnel with SUD who were not engaged in SUD treatment (n = 242; 92.1% male). We compared three groups with complete data on baseline and 3-month provisional PTSD: individuals without provisional PTSD at baseline (n = 98), those with provisional PTSD remitted by 3 months (n = 42), and those with provisional PTSD unremitted at 3 months (n = 53) on alcohol use frequency, quantity, consequences, and related diagnoses. RESULTS: Individuals with unremitted provisional PTSD were at increased risk for moderate/severe alcohol use disorder at 6 months relative to those without baseline provisional PTSD (odds ratio = 4.53, p = .007). The effect of MET on drinks per week at 6 months (controlling for baseline) differed with a significant effect of MET for individuals with remitted provisional PTSD (count ratio = 0.41, p = .005). CONCLUSIONS: Both interventions were effective in reducing drinking even for those with provisional PTSD, although, compared with education, MET had slightly better effects on reducing drinking quantity for those with remitted PTSD. Findings suggest that PTSD remission may serve as an early prognostic indicator of long-term alcohol use changes, or alternatively, delivery of MET during heightened transitory distress may be most effective for reducing alcohol use.

Young adults with psychosis: Intentions for cannabis reduction and cessation based on theory of planned behavior.

OBJECTIVE: Young adults experiencing a first episode of psychosis (FEP) have high rates of cannabis use and cannabis use disorder (CUD). No evidence-based practice effectively treats CUD for people with FEP, and little is known about factors that influence intentions to reduce or stop using. A critical inquiry was conducted to identify salient factors contributing to intentions of young adults with FEP to reduce or discontinue cannabis use, guided by theory of planned behavior (TPB). METHOD: Online focus groups (n = 3) and individual interviews (n = 3) were conducted with 16 young adults with FEP (mean age of 23.7) and historical cannabis use (averaging 11.8 days of use in the previous 30). A content analysis was conducted to sort data into TPB constructs, and a thematic analysis was subsequently performed to identify the breadth of themes. RESULTS: Participants identified benefits of cannabis reduction and cessation for pursuing life goals, but most maintained regular use. Participants perceived cannabis as a facilitator of social interactions, enjoyable activities, and improved mental health (and reduced dysthymia). Many were concerned about reducing or discontinuing cannabis without replacement strategies to compensate for its benefits. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: In spite of life goals incompatible with cannabis use, cessation was not favored given the perceived benefits of cannabis and participants' lack of replacement strategies to facilitate social interactions, enjoyable activities, and euthymia. Interventions may be improved by addressing motivations for use and by teaching skills to build positive social support, schedule enjoyable activities, and ameliorate dysthymia. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Development of StressCheck: A telehealth motivational enhancement therapy to improve voluntary engagement for PTSD treatment among active-duty service members.

BACKGROUND: Rates of PTSD in active-duty military are high relative to the general population. Although efficacious treatments exist, they are underutilized. Many service members with PTSD do not present for treatment and, of those who do, many do not receive sufficient doses of the interventions to receive full benefits. Motivational Enhancement Therapy (MET) "check-ups", are brief interventions designed to elicit treatment engagement for those who are not treatment-seeking. METHODS: StressCheck is an MET for nontreatment seeking Army and Air Force personnel. StressCheck aims to improve PTSD and increase treatment engagement, especially around evidence-based interventions, as well as to decrease stigma about seeking mental health services and improve knowledge about treatment options. This paper describes the intervention components and process of treatment development. The paper also describes next steps in testing the effectiveness of the intervention. CONCLUSION: PTSD is associated with deleterious health, occupational, and psychological effects. If effective, this innovative intervention will bridge the gap between those who are not treatment seeking and existing services, thereby enhancing reach and impact of existing services. GOV IDENTIFIER: NCT03423394.

Barriers to Implementing a Cannabis Focused SBIRT in Adolescent Primary Care.

Introduction: The current study investigated providers' perceived barriers, supports, and need for adopting a screening, brief intervention, and referral to treatment model (SBIRT) intervention related to cannabis reduction into their community based primary care clinics. Methods: Eleven pediatric primary care providers from regional community-based clinics participated in focus groups discussing a proposed adolescent cannabis use SBIRT reduction intervention, perceived need, and potential barriers to implementation within their clinic. Results: Seven primary themes emerged regarding barriers to implementing a cannabis reduction SBIRT in primary care including provider ambivalence to adolescent cannabis use. Conclusion: Further research is needed to understand evolving provider perceptions of adolescent cannabis use and how these views impact the adoption of SBIRT for the reduction of cannabis use among their adolescent patients.

Distinct roles for two Caenorhabditis elegans acid-sensing ion channels in an ultradian clock.

Biological clocks are fundamental to an organism's health, controlling periodicity of behaviour and metabolism. Here, we identify two acid-sensing ion channels, with very different proton sensing properties, and describe their role in an ultradian clock, the defecation motor program (DMP) of the nematode Caenorhabditis elegans. An ACD-5-containing channel, on the apical membrane of the intestinal epithelium, is essential for maintenance of luminal acidity, and thus the rhythmic oscillations in lumen pH. In contrast, the second channel, composed of FLR-1, ACD-3 and/or DEL-5, located on the basolateral membrane, controls the intracellular Ca2+ wave and forms a core component of the master oscillator that controls the timing and rhythmicity of the DMP. flr-1 and acd-3/del-5 mutants show severe developmental and metabolic defects. We thus directly link the proton-sensing properties of these channels to their physiological roles in pH regulation and Ca2+ signalling, the generation of an ultradian oscillator, and its metabolic consequences.

Biological clocks regulate a myriad of processes that occur periodically, from sleeping and waking to how cells use nutrients and energy. One such clock is the one that controls intestinal movements and defecation in the nematode worm Caenorhabditis elegans, which consists of three muscle contractions occurring every 50 seconds. This rhythm is controlled by calcium and proton signalling in the cells of the intestine. The cells of the nematode intestine form a tube, through which gut contents pass. The inside of the tube is acidic, but acidity also plays a role on the outer face of the intestinal tube. In this area, nutrients are distributed and signals are conveyed to other tissues, such as muscles. In fact, acid ­ in the form of protons ­ secreted from the intestinal cells stimulates the muscles that contract in the biological clock that controls the worms' defecation. However, it is poorly understood how the worms control the release of these protons. Kaulich et al. identified two ion channels on the membranes of intestinal cells that become inhibited when the levels of acid surrounding them are high. These channels play distinct roles in controlling the contractions that move the contents of the roundworms' intestines along. The first channel contains a protein called ACD-5, and it is in the membrane of the intestinal cells that faces the inside of the intestinal tube. The second channel is formed by three proteins: FLR-1, ACD-3 and DEL-5. This channel is found on the other side of the intestinal cells, the region where nutrients are distributed and signals are conveyed to the rest of the body. To determine the role of each channel, Kaulich et al. genetically engineered the worms so they would not make the proteins that make up the channels, and imaged the live nematodes to see the effects of removing each channel. The inside of the intestines of worms lacking the ACD-5 containing channel was less acidic than that of normal worms, and the timing of the contractions that control defecation was also slightly altered. Removing the second channel (the one formed by three different proteins), however, had more dramatic effects: the worms were thin, developed more slowly, had less fat tissue and defecated very irregularly. Kaulich et al. imaged live worms to show that the second channel plays a major role in regulating oscillations in acidity both inside and outside cells, as well as controlling calcium levels. This demonstrates that this channel is responsible for the rhythmicity in the contractions that control defecation in the nematodes. Their findings provide important insights towards better understanding proton signalling and the role of acid-sensing ion channels in cellular contexts and biological clocks.

Adapting narrative exposure therapy with a tribal community: A community-based approach.

OBJECTIVE: American Indian (AI) individuals are at increased risk for present-day trauma exposure and associated negative outcomes, as well as ongoing effects of intergenerational trauma exposure and adversity. However, few empirically supported treatments exist that are specifically tailored and/or tested with AI communities. This study describes the process of selecting, adapting, and implementing narrative exposure therapy (NET) with an AI community. METHODS: A community and academic partnership was formed and worked together to make culturally mindful changes to NET to best fit the needs of the community. The partnership incorporated community leaders/Elders (n = 7), providers (n = 11), and participants seeking treatment (n = 50) to implement an iterative process of adapting and implementing the adapted form of NET. RESULTS: Key adaptions included addressing historical and intergenerational trauma, greater protections for confidentiality in a small community, and incorporation of cultural customs and traditions. Overall, the adapted form of NET was favorably received by the participants, and the implementation appeared to be feasible, with improved retention over past trials of adapted trauma-focused treatments with this community and with highly positive satisfaction ratings and feedback. CONCLUSIONS: NET was shown to be an appropriate approach for this AI community and should be considered as a treatment option for other AI communities. Future work should consider strategies outlined in this adaption as well as following a similar process for working with AI communities to implement culturally appropriate interventions for trauma-related symptoms.

The Caenorhabditis elegans tmc-1 is involved in egg-laying inhibition in response to harsh touch.

The conserved family of Transmembrane channel-like (TMC) proteins has attracted significant interest since two members appear to be key components of the mammalian hair cell mechanotransducer involved in hearing. C. elegans expresses two TMC proteins, TMC-1 and TMC-2. TMC-1 is widely expressed in in both muscles and the nervous system. This wide expression pattern suggests that TMC-1 might serve different functions in the various neurons. TMC-1 has previously been shown to function in neurons, playing a role in chemosensation in the ASH neurons and mechanosensation in OLQ neurons, further supporting this hypothesis. tmc-1 is expressed in the high-threshold mechanosensory neuron, ALA. We show that tmc-1 mutants show defects in the ALA-dependent inhibition of egg-laying in response to a harsh mechanical stimulus.

Interventions for cannabis use disorder.

How to treat adults and adolescents with a Cannabis Use Disorder is a burgeoning research area. This article reviews the empirical literature pertaining to several psychosocial approaches (cognitive-behavior therapy, motivational enhancement, and contingency management), all of which are associated with favorable outcomes. We also review the emerging research on the use of pharmacotherapy, brief interventions and technology-delivered interventions, and conclude with an overview of future research needs.