An Open-Label, Randomized Trial Comparing Fidaxomicin With Oral Vancomycin for the Treatment of Clostridioides difficile Infection in Hospitalized Patients Receiving Concomitant Antibiotics for Concurrent Infections.

BACKGROUND: Recurrent Clostridioides difficile infection (rCDI) occurs frequently, and concomitant antibiotic (CA) during the initial episode for treatment of non-CDI is a major risk factor. We sought to address the comparative efficacy of fidaxomicin versus vancomycin in the setting of CA during the initial CDI episode. METHODS: We conducted a randomized, controlled, open-label trial at 2 hospitals in Ann Arbor, Michigan. We consecutively consented and enrolled hospitalized patients ≥18 years old with diarrhea, a positive test for C. difficile, and ≥1 qualifying CA. Complicated CDI, CDI treatment for >24 hours prior to enrollment, and planned long-term (>12 weeks) CA use were notable exclusions. Clinical cure was defined as resolution of diarrhea for 2 consecutive days maintained until 2 days after therapy, and rCDI as recurrent diarrhea with positive testing ≤30 days after initial treatment. Patients were randomized to fidaxomicin or vancomycin. RESULTS: Baseline characteristics were similar in the 2 groups of 144 patients. Rates of clinical cure (73% vs 62.9%, P = .195) and rCDI (3.3% vs 4.0%; P > .99) were similar for fidaxomicin and vancomycin in the intention-to-treat and per-protocol cohorts, respectively. Only 4 patients developed rCDI. CONCLUSIONS: In this study of patients with CDI receiving CA, a numerically higher proportion were cured with fidaxomicin versus vancomycin, but this result did not reach statistical significance. Overall recurrence was lower than anticipated in both arms compared with previous studies that did not extend duration of CDI treatment during CA. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT02692651).

Crystal structure of human PLD1 provides insight into activation by PI(4,5)P2 and RhoA.

The signal transduction enzyme phospholipase D1 (PLD1) hydrolyzes phosphatidylcholine to generate the lipid second-messenger phosphatidic acid, which plays roles in disease processes such as thrombosis and cancer. PLD1 is directly and synergistically regulated by protein kinase C, Arf and Rho GTPases, and the membrane lipid phosphatidylinositol-4,5-bisphosphate (PIP2). Here, we present a 1.8 Å-resolution crystal structure of the human PLD1 catalytic domain, which is characterized by a globular fold with a funnel-shaped hydrophobic cavity leading to the active site. Adjacent is a PIP2-binding polybasic pocket at the membrane interface that is essential for activity. The C terminus folds into and contributes part of the catalytic pocket, which harbors a phosphohistidine that mimics an intermediate stage of the catalytic cycle. Mapping of PLD1 mutations that disrupt RhoA activation identifies the RhoA-PLD1 binding interface. This structure sheds light on PLD1 regulation by lipid and protein effectors, enabling rationale inhibitor design for this well-studied therapeutic target.

Trans individuals' experiences in primary care.

OBJECTIVE: To explore past experiences and describe the expectations of members of the trans community regarding the delivery of primary care by their family physicians. DESIGN: Qualitative phenomenologic approach. SETTING: Kingston, Ont, which has a population of approximately 123 000. PARTICIPANTS: A convenience sample of 11 individuals older than 18 years of age who self-identified as trans was recruited through community agencies and family medicine clinics. METHODS: Semistructured interviews were recorded and transcribed verbatim, and thematic analysis of transcripts was carried out by 2 independent researchers using NVivo. MAIN FINDINGS: Eleven interviews took place between September and November 2016; 4 individuals identified as trans men, 6 as trans women, and 1 as gender nonconforming. Themes identified included perceived physician knowledge of trans identities, patient self-advocacy, discrimination, positive spaces, and expectations of ideal care. The expected role of the family physician for trans patients includes hormone assessment and prescription and referrals for gender-affirming surgeries. CONCLUSION: The trans community has several physical and mental health needs that are not being met by the current health care system. Family physicians need to be empowered to provide services such as hormone initiation and gender-affirming surgery referrals. Although other specialists might have a role for some patients, most trans people expect care to be delivered by family physicians whenever possible.

Sulfate transporters involved in sulfate secretion in the kidney are localized in the renal proximal tubule II of the elephant fish (Callorhinchus milii).

Most vertebrates, including cartilaginous fishes, maintain their plasma SO4 (2-) concentration ([SO4 (2-)]) within a narrow range of 0.2-1 mM. As seawater has a [SO4 (2-)] about 40 times higher than that of the plasma, SO4 (2-) excretion is the major role of kidneys in marine teleost fishes. It has been suggested that cartilaginous fishes also excrete excess SO4 (2-) via the kidney. However, little is known about the underlying mechanisms for SO4 (2-) transport in cartilaginous fish, largely due to the extraordinarily elaborate four-loop configuration of the nephron, which consists of at least 10 morphologically distinguishable segments. In the present study, we determined cDNA sequences from the kidney of holocephalan elephant fish (Callorhinchus milii) that encoded solute carrier family 26 member 1 (Slc26a1) and member 6 (Slc26a6), which are SO4 (2-) transporters that are expressed in mammalian and teleost kidneys. Elephant fish Slc26a1 (cmSlc26a1) and cmSlc26a6 mRNAs were coexpressed in the proximal II (PII) segment of the nephron, which comprises the second loop in the sinus zone. Functional analyses using Xenopus oocytes and the results of immunohistochemistry revealed that cmSlc26a1 is a basolaterally located electroneutral SO4 (2-) transporter, while cmSlc26a6 is an apically located, electrogenic Cl(-)/SO4 (2-) exchanger. In addition, we found that both cmSlc26a1 and cmSlc26a6 were abundantly expressed in the kidney of embryos; SO4 (2-) was concentrated in a bladder-like structure of elephant fish embryos. Our results demonstrated that the PII segment of the nephron contributes to the secretion of excess SO4 (2-) by the kidney of elephant fish. Possible mechanisms for SO4 (2-) secretion in the PII segment are discussed.

Morphological and molecular investigations of the holocephalan elephant fish nephron: the existence of a countercurrent-like configuration and two separate diluting segments in the distal tubule.

In marine cartilaginous fish, reabsorption of filtered urea by the kidney is essential for retaining a large amount of urea in their body. However, the mechanism for urea reabsorption is poorly understood due to the complexity of the kidney. To address this problem, we focused on elephant fish (Callorhinchus milii) for which a genome database is available, and conducted molecular mapping of membrane transporters along the different segments of the nephron. Basically, the nephron architecture of elephant fish was similar to that described for elasmobranch nephrons, but some unique features were observed. The late distal tubule (LDT), which corresponded to the fourth loop of the nephron, ran straight near the renal corpuscle, while it was convoluted around the tip of the loop. The ascending and descending limbs of the straight portion were closely apposed to each other and were arranged in a countercurrent fashion. The convoluted portion of LDT was tightly packed and enveloped by the larger convolution of the second loop that originated from the same renal corpuscle. In situ hybridization analysis demonstrated that co-localization of Na(+),K(+),2Cl(-) cotransporter 2 and Na(+)/K(+)-ATPase α1 subunit was observed in the early distal tubule and the posterior part of LDT, indicating the existence of two separate diluting segments. The diluting segments most likely facilitate NaCl absorption and thereby water reabsorption to elevate urea concentration in the filtrate, and subsequently contribute to efficient urea reabsorption in the final segment of the nephron, the collecting tubule, where urea transporter-1 was intensely localized.

Discovery of conventional prolactin from the holocephalan elephant fish, Callorhinchus milii.

The conventional prolactin (PRL), also known as PRL1, is an adenohypophysial hormone that critically regulates various physiological events in reproduction, metabolism, growth, osmoregulation, among others. PRL1 shares its evolutionary origin with PRL2, growth hormone (GH), somatolactin and placental lactogen, which together form the GH/PRL hormone family. Previously, several bioassays implied the existence of PRL1 in elasmobranch pituitaries. However, to date, all attempts to isolate PRL1 from chondrichthyans have been unsuccessful. Here, we cloned PRL1 from the pituitary of the holocephalan elephant fish, Callorhinchus milii, as the first report of chondrichthyan PRL1. The putative mature protein of elephant fish PRL1 (cmPRL1) consists of 198 amino acids, containing two conserved disulfide bonds. The orthologous relationship of cmPRL1 to known vertebrate PRL1s was confirmed by the analyses of molecular phylogeny and gene synteny. The cmPRL1 gene was similar to teleost PRL1 genes in gene synteny, but was distinct from amniote PRL1 genes, which most likely arose in an early amphibian by duplication of the ancestral PRL1 gene. The mRNA of cmPRL1 was predominantly expressed in the pituitary, but was considerably less abundant than has been previously reported for bony fish and tetrapod PRL1s; the copy number of cmPRL1 mRNA in the pituitary was less than 1% and 0.1% of that of GH and pro-opiomelanocortin mRNAs, respectively. The cells expressing cmPRL1 mRNA were sparsely distributed in the rostral pars distalis. Our findings provide a new insight into the studies on molecular and functional evolution of PRL1 in vertebrates.

Urea-based osmoregulation in the developing embryo of oviparous cartilaginous fish (Callorhinchus milii): contribution of the extraembryonic yolk sac during the early developmental period.

Marine cartilaginous fish retain a high concentration of urea to maintain the plasma slightly hyperosmotic to the surrounding seawater. In adult fish, urea is produced by hepatic and extrahepatic ornithine urea cycles (OUCs). However, little is known about the urea retention mechanism in developing cartilaginous fish embryos. In order to address the question as to the mechanism of urea-based osmoregulation in developing embryos, the present study examined the gene expression profiles of OUC enzymes in oviparous holocephalan elephant fish (Callorhinchus milii) embryos. We found that the yolk sac membrane (YSM) makes an important contribution to the ureosmotic strategy of the early embryonic period. The expression of OUC enzyme genes was detectable in the embryonic body from at least stage 28, and increased markedly during development to hatching, which is most probably due to growth of the liver. During the early developmental period, however, the expression of OUC enzyme genes was not prominent in the embryonic body. Meanwhile, we found that the mRNA expression of OUC enzymes was detected in the extra-embryonic YSM; the mRNA expression of cmcpsIII in the YSM was much higher than that in the embryonic body during stages 28-31. Significant levels of enzyme activity and the existence of mitochondrial-type cmgs1 transcripts in the YSM supported the mRNA findings. We also found that the cmcpsIII transcript is localized in the vascularized inner layer of the YSM. Taken together, our findings demonstrate for the first time that the YSM is involved in urea-based osmoregulation during the early to mid phase of development in oviparous cartilaginous fish.

Holocephalan embryos provide evidence for gill arch appendage reduction and opercular evolution in cartilaginous fishes.

Chondrichthyans possess endoskeletal appendages called branchial rays that extend laterally from their hyoid and gill-bearing (branchial) arches. Branchial ray outgrowth, like tetrapod limb outgrowth, is maintained by Sonic hedgehog (Shh) signaling. In limbs, distal endoskeletal elements fail to form in the absence of normal Shh signaling, whereas shortened duration of Shh expression correlates with distal endoskeletal reduction in naturally variable populations. Chondrichthyans also exhibit natural variation with respect to branchial ray distribution--elasmobranchs (sharks and batoids) possess a series of ray-supported septa on their hyoid and gill arches, whereas holocephalans (chimaeras) possess a single hyoid arch ray-supported operculum. Here we show that the elongate hyoid rays of the holocephalan Callorhinchus milii grow in association with sustained Shh expression within an opercular epithelial fold, whereas Shh is only transiently expressed in the gill arches. Coincident with this transient Shh expression, branchial ray outgrowth is initiated in C. milii but is not maintained, yielding previously unrecognized vestigial gill arch branchial rays. This is in contrast to the condition seen in sharks, where sustained Shh expression corresponds to the presence of fully formed branchial rays on the hyoid and gill arches. Considered in light of current hypotheses of chondrichthyan phylogeny, our data suggest that the holocephalan operculum evolved in concert with gill arch appendage reduction by attenuation of Shh-mediated branchial ray outgrowth, and that chondrichthyan branchial rays and tetrapod limbs exhibit parallel developmental mechanisms of evolutionary reduction.

Postoperative Nausea and Vomiting in the Ambulatory Surgery Center: A Narrative Review.

Postoperative nausea and vomiting (PONV) is a common complication of ambulatory surgery, leading to numerous deleterious effects such as decreased patient satisfaction, prolonged recovery unit stays, and rarely, more serious complications such as aspiration pneumonia or wound dehiscence. In this paper, we present a narrative review of the literature regarding common risk factors for PONV including patient factors, surgical factors, and anesthetic factors. We then will review anesthetic techniques and antiemetic drugs demonstrated to mitigate the risk of PONV. Finally, we discuss the potential economic benefits of PONV prophylaxis in the perioperative ambulatory setting.

Effects of strength of relationship ties in recovery homes: A conundrum.

Recovery homes are a widespread source of support for those attempting to maintain abstinence. For those who are able to remain in these settings for at least 6 months, outcomes tend to be favorable; however, many leave prematurely. There is a need to better understand the social integration processes that play a major role in giving recovery home residents access to available recovery-related social capital that is associated with better outcomes. The current study involved Oxford House recovery homes in 3 states and examined the strength of relationship ties among house members. We found that those who associated with peers who have higher recovery scores tend to improve their own recovery scores over time. However, we also found that those with higher recovery scores tended to create "strong" ties with similarly high-scoring alters; likewise lower-scoring individuals preferentially formed strong ties with each other. These findings suggest a conundrum: recovery home residents most in need of relational support from more recovered housemates are the least likely to obtain it. We discuss possible pathways to creating more ties between high and low-recovered residents.

"A lot of moving parts": Recovery home challenges linking and housing individuals with criminal legal system involvement.

INTRODUCTION: There are high rates of substance use disorder (SUD) among people released from carceral settings and, upon release, many of these people also face unstable housing situations, posing challenges to connecting with resources to facilitate SUD recovery. Recovery homes provide a temporary sober living environment for those seeking both SUD recovery and transition back to the community after carceral release. However, successful recovery home placement for this population can prove difficult, and there is a need for research to identify ways to overcome them. METHODS: The current qualitative study seeks to understand barriers to recovery home access for people leaving carceral settings and identify potential best practices for overcoming these barriers from the perspective of recovery home directors. The study conducted semi-structured interviews at two data collection points with eight recovery home directors from sites participating in a housing linkage and placement intervention pilot. The research team used qualitative software to identify and organize directors' experiences and practices in housing and supporting this population. RESULTS: Recovery home directors identified significant barriers to linkage from carceral settings, including difficulties communicating and coordinating placement with potential residents while still incarcerated. Interviews also revealed approaches recovery home directors take to improve recovery home placement, such as sharing information and resources with carceral settings prior to release and helping residents avoid reincarceration by managing relationships with court agents and parole. CONCLUSION: Recovery resident directors have considerable insight into the most significant placement challenges faced by recovery homes upon carceral release as well as experience with potential solutions for overcoming them. Directors can be the key to direct seamless support and continuity of care for criminal legal system involved individuals through coordination with jails, prisons, and other community resources. Directors can also play a significant role in the successful completion of probation and parole by helping residents avoid further issues with the legal system. These directors view working cooperatively with residents as an effective approach to ensuring clients adhere to court orders and are successful in recovery and reentry.

Learning with conviction: Exploring the relationship between criminal legal system involvement and substance use and recovery outcomes for students in collegiate recovery programs.

This study examines the association of criminal legal system involvement and age with substance use and academic related outcomes among students involved in collegiate recovery programs in the US. We examined 435 students in collegiate recovery using a national survey of college students. We computed differences between non-system-involved, system-involved with no incarceration history, and formerly incarcerated participants on relevant substance use and recovery-related outcomes. The results provide evidence that there are significant differences between those system-involved and those who are not. Specifically, we found significant differences across the outcomes of recovery capital, quality of life, hours worked per week, and substance use disorder symptoms, but after controlling for relevant covariates, only the differences between hours worked (non-system involved and system involved < formerly incarcerated) and substance use disorder symptoms (non-system involved < system involved and formerly incarcerated) remained significant. The study contributes to the literature by demonstrating that nearly half of the collegiate students in recovery in this sample have legal system-involvement and a third have been incarcerated. Further, interventions for collegiate recovery programs may need to be adjusted to account for legal system involvement among their members.

Workforce outcomes among substance use peer supports and their contextual determinants: A scoping review protocol.

Background: Peer recovery support services are a promising approach for improving harm reduction, treatment, and recovery-related outcomes for people who have substance use disorders. However, unique difficulties associated with the role may put peer recovery support staff (i.e., peers) at high risk for negative workforce outcomes, including burnout, vicarious trauma, and compassion fatigue, which impact one's personal recovery journey. Little is known about the extent to which peers experience such negative outcomes or the influence the service setting context has upon them. This scoping review aims to describe the nature and extent of research evidence on peers' workforce outcomes and how these outcomes might differ across service settings. Methods: A scoping review will be conducted with literature searches conducted in PsycINFO®, (EBSCO), Embase® (EBSCO), CINAHL® (EBSCO), Web of Science™ (Clarivate), and Google Scholar databases for relevant articles discussing US-based research and published in English from 1 January 1999 to 1 August 2023. The study will include peer-reviewed and grey-literature published materials describing the experiences of peers participating in recovery support services and harm reduction efforts across a variety of service settings. Two evaluators will independently review the abstracts and full-text articles. We will perform a narrative synthesis, summarizing and comparing the results across service settings. Conclusions: This review will assess the state of the literature on peer workforce-related outcomes and how outcomes might vary by service setting context. Exploration will include individual characteristics of peers that moderate workforce outcomes, and workforce outcomes that mediate personal recovery outcomes. Results will inform the field regarding future directions for research in this area. Systematic review registration: Submitted to Open Science Framework, August 22nd, 2023.

Estimation of effective number of breeders and effective population size in an abundant and heavily exploited marine teleost.

Obtaining reliable estimates of the effective number of breeders (N b) and generational effective population size (N e) for fishery-important species is challenging because they are often iteroparous and highly abundant, which can lead to bias and imprecision. However, recent advances in understanding of these parameters, as well as the development of bias correction methods, have improved the capacity to generate reliable estimates. We utilized samples of both single-cohort young of the year and mixed-age adults from two geographically and genetically isolated stocks of the Australasian snapper (Chrysophrys auratus) to investigate the feasibility of generating reliable N b and N e estimates for a fishery species. Snapper is an abundant, iteroparous broadcast spawning teleost that is heavily exploited by recreational and commercial fisheries. Employing neutral genome-wide SNPs and the linkage-disequilibrium method, we determined that the most reliable N b and N e estimates could be derived by genotyping at least 200 individuals from a single cohort. Although our estimates made from the mixed-age adult samples were generally lower and less precise than those based on a single cohort, they still proved useful for understanding relative differences in genetic effective size between stocks. The correction formulas applied to adjust for biases due to physical linkage of loci and age structure resulted in substantial upward modifications of our estimates, demonstrating the importance of applying these bias corrections. Our findings provide important guidelines for estimating N b and N e for iteroparous species with large populations. This work also highlights the utility of samples originally collected for stock structure and stock assessment work for investigating genetic effective size in fishery-important species.

Expression of Wnt signaling skeletal development genes in the cartilaginous fish, elephant shark (Callorhinchus milii).

Jawed vertebrates (Gnasthostomes) are broadly separated into cartilaginous fishes (Chondricthyes) and bony vertebrates (Osteichthyes). Cartilaginous fishes are divided into chimaeras (e.g. ratfish, rabbit fish and elephant shark) and elasmobranchs (e.g. sharks, rays and skates). Both cartilaginous fish and bony vertebrates are believed to have a common armoured bony ancestor (Class Placodermi), however cartilaginous fish are believed to have lost bone. This study has identified and investigated genes involved in skeletal development in vertebrates, in the cartilaginous fish, elephant shark (Callorhinchus milii). Ctnnb1 (ß-catenin), Sfrp (secreted frizzled protein) and a single Sost or Sostdc1 gene (sclerostin or sclerostin domain-containing protein 1) were identified in the elephant shark genome and found to be expressed in a number of tissues, including cartilage. ß-catenin was also localized in several elephant shark tissues. The expression of these genes, which belong to the Wnt/ß-catenin pathway, is required for normal bone formation in mammals. These findings in the cartilaginous skeleton of elephant shark support the hypothesis that the common ancestor of cartilaginous fishes and bony vertebrates had the potential for making bone.

Drinking to cope and coping strategies in Deaf/Hard of hearing college students.

INTRODUCTION: Deaf and hard of hearing (DHH) students experience unique stressors as a minority linguistic and cultural group that may contribute to problematic substance and alcohol use behavior. Proper coping strategies may be one protective factor to avoid reliance on alcohol as a means to reduce stress. METHODS: The current study compared the endorsement of coping strategies by DHH students and hearing individuals and their relationship to drinking to cope behavior. Data was collected among DHH (n = 126) and hearing students (n = 349) at a large university. RESULTS: While these two groups did not differ in their levels of problematic drinking behavior, there were differences observed in drinking to cope motives as well as in the levels of coping styles used. DHH students were found to endorse greater levels of emotion-oriented and task-oriented coping than hearing students. Drinking to cope motivations were also higher for DHH students, particularly those who endorsed greater emotion focused coping. CONCLUSIONS: Interventions and educational efforts involving coping skills is a potentially important area of focus for the DHH student population. Further implications for understanding drinking behavior in this population are discussed.

Fishery independent survey datasets of abalone populations on subtidal coastal reefs in southeastern Australia.

Assessing the status or exploited marine fish populations often relies on fishery dependent catch and effort data reported by licensed commercial fishers in compliance with regulations and by recreational anglers voluntarily. This invariably leads to bias towards the fraction of a fish population or community that can be legally fished i.e., the stock as defined by legal minimum lengths and spatial boundaries. Data are restricted to populations which continue to be exploited at the expense of obtaining data on previously exploited and unexploited populations [1,2], so if a fishery is contracting spatially over time, then successively less of the overall fish community is monitored with bias towards where biomass is highest or most accessible [3]. A viable alternative is to conduct population monitoring surveys independently of a fishery to obtain information that is more broadly representative of the abundance, composition and size structure of fish communities and their supporting habitats [4-6]. Whereas catch and effort data often must be de-identified and aggregated to protect the confidentiality of fishers' commercial and personal interests, this constraint does not exist for independently acquired monitoring data, collected at public expense and hence publicly available at high levels of spatial and temporal resolution. Time series underpins the utility of fishery independent survey (FIS) datasets in terms of the life histories of exploited fish species and the time frames of their responses to various combinations of fishing mortality and environmental fluctuations and trends [7]. One-off surveys can establish a baseline and spatial distribution pattern, but regular surveys conducted consistently over time are necessary to detect trends from which population status can be inferred. We present several unique datasets focused on the commercially valuable blacklip abalone (Haliotis rubra), spanning three decades of annually collected data from up to 204 locations on subtidal rocky reefs along a coastline of almost 2500 km, the State of Victoria, Australia. It is rare for data to be collected consistently at this intensity over such a long period of monitoring [2], especially with surveys conducted by small teams of highly skilled research divers, some of whom up until recently had participated in every year. The data comprises ∼28,000 records from ∼4500 site surveys conducted during 1992 to 2021 [2]. Although the fixed site design remained unchanged, the number of sites surveyed varied over time, mostly increasing in number periodically, and the survey method was refined on several occasions. We defined three different variants in the survey method due to technological advancement for both enumerating abalone abundance and measuring shell size structure [7]. The relative abundance counts were standardized using a Bayesian generalized linear mixed model (GLMM) to test for interannual trends whilst allowing for inherent differences among sites, research divers, and their interactions [8].

Spiritual Awakening in 12-Step Recovery: Impact Among Residential Aftercare Residents.

Spiritually-based interventions in the form of 12-step programs are frequently offered as a part of substance use treatment programs in the United States. Programs based in the 12 steps guarantee that by working their program, an individual will undergo a process of transformation labeled a spiritual awakening. However, the impact of this experience on recovery factors and treatment adherence is unclear. The current study investigated adult residents (n = 115) who experienced a spiritual awakening attributed to 12-step group affiliation during their stay at residential aftercare facilities for substance use disorder. Self-efficacy and hope were greater for individuals who experienced a spiritual awakening versus those persons who did not experience awakening. Awakening was associated with greater affiliation to AA and decreased negative exit from the facility. Results revealed the potential for an awakening to improve treatment behavior and outcomes in a residential environment, as well as benefit an individual's personal recovery resources. Further theoretical and clinical implications are discussed.

The fifth neurohypophysial hormone receptor is structurally related to the V2-type receptor but functionally similar to V1-type receptors.

The neurohypophysial peptides of the vasopressin (VP) and oxytocin (OT) families regulate salt and water homeostasis and reproduction through distinct G protein-coupled receptors. The current thinking is that there are four neurohypophysial hormone receptors (V1aR, V1bR, V2R, and OTR) in vertebrates, and their evolutionary history is still debated. We report the identification of a fifth neurohypophysial hormone receptor (V2bR) from the holocephalan elephant fish. This receptor is similar to conventional V2R (V2aR) in sequence, but induced Ca(2+) signaling in response to vasotocin (VT), the non-mammalian VP ortholog; such signaling is typical of V1-type receptors. In addition, V1aR, V1bR and OTR were also isolated from the elephant fish. Further screening revealed that orthologous V2bRs are widely distributed throughout the jawed vertebrates, and that the V2bR family is subdivided into two subfamilies: the fish specific type-1, and a type-2 that is characteristically found in tetrapods. Analysis suggested that the mammalian V2bR may have lost its function. Based on molecular phylogenetic, synteny and functional analyses, we propose a new evolutionary history for the neurohypophysial hormone receptors in vertebrates as follows: the first duplication generated V1aR/V1bR/OTR and V2aR/V2bR lineages; after divergence from the V2bR lineage, the V2aRs evolved to use cAMP as a second messenger, while the V2bRs retained the original Ca(2+) signaling system. Future studies on the role of V2bR in the brain, heart, kidney and reproductive organs, in which it is highly expressed, will open a new research field in VP/VT physiology and evolution.

A substance user-self fit perception increases identification as a user of the substance.

We tested whether greater identification as a user of a substance (i.e., perceived general associations between oneself and use of the substance, the group of people who use the substance, and/or the substance itself) results from a theorized source-perceived fit between one's own identity and one's perception of the identity of being a user of the substance. We also tested whether this effect is stronger the more the group of people who use the substance is perceived as an entity and the more the prototypical user of the substance is perceived as having a favorable identity. We conducted two correlational and two (preregistered) experimental investigations of drinker identity and marijuana user identity. In all studies, substance user identity was positively associated with substance user-self fit perception. In both correlational studies, this relationship was stronger the more the group of people who use the substance was perceived as an entity. In the drinker identity correlational study, this relationship was also stronger the more it was perceived that the prototypical drinker has a favorable identity. A substance user-self fit perception could be addressed to reduce identification as a user of the substance in efforts to prevent hazardous use. (PsycInfo Database Record (c) 2023 APA, all rights reserved).