Publisher Correction: Martian dust storm impact on atmospheric H2O and D/H observed by ExoMars Trace Gas Orbiter.

The surname of author Cathy Quantin-Nataf was misspelled 'Quantin-Nata' , authors Ehouarn Millour and Roland Young were missing from the ACS Science Team list, and minor changes have been made to the author and affiliation lists; see accompanying Amendment. These errors have been corrected online.

Martian dust storm impact on atmospheric H2O and D/H observed by ExoMars Trace Gas Orbiter.

Global dust storms on Mars are rare1,2 but can affect the Martian atmosphere for several months. They can cause changes in atmospheric dynamics and inflation of the atmosphere3, primarily owing to solar heating of the dust3. In turn, changes in atmospheric dynamics can affect the distribution of atmospheric water vapour, with potential implications for the atmospheric photochemistry and climate on Mars4. Recent observations of the water vapour abundance in the Martian atmosphere during dust storm conditions revealed a high-altitude increase in atmospheric water vapour that was more pronounced at high northern latitudes5,6, as well as a decrease in the water column at low latitudes7,8. Here we present concurrent, high-resolution measurements of dust, water and semiheavy water (HDO) at the onset of a global dust storm, obtained by the NOMAD and ACS instruments onboard the ExoMars Trace Gas Orbiter. We report the vertical distribution of the HDO/H2O ratio (D/H) from the planetary boundary layer up to an altitude of 80 kilometres. Our findings suggest that before the onset of the dust storm, HDO abundances were reduced to levels below detectability at altitudes above 40 kilometres. This decrease in HDO coincided with the presence of water-ice clouds. During the storm, an increase in the abundance of H2O and HDO was observed at altitudes between 40 and 80 kilometres. We propose that these increased abundances may be the result of warmer temperatures during the dust storm causing stronger atmospheric circulation and preventing ice cloud formation, which may confine water vapour to lower altitudes through gravitational fall and subsequent sublimation of ice crystals3. The observed changes in H2O and HDO abundance occurred within a few days during the development of the dust storm, suggesting a fast impact of dust storms on the Martian atmosphere.

Selective neural inhibition via photobiomodulation alleviates behavioral hypersensitivity associated with small sensory fiber activation.

OBJECTIVE: Photobiomodulation at higher irradiances has great potential as a pain-alleviating method that selectively inhibits small diameter nerve fibers and corresponding sensory experiences, such as nociception and heat sensation. The longevity and magnitude of these effects as a function of laser irradiation parameters at the nerve was explored. METHODS: In a rodent chronic pain model (spared nerve injury-SNI), light was applied directly at the sural nerve with four delivery schemes: two irradiance levels (7.64 and 2.55 W/cm2 ) for two durations each, corresponding to either 4.8 or 14.4 J total energy, and the effect on sensory hypersensitivities was evaluated. RESULTS: At emitter irradiances of 7.64 W/cm2 (for 240 s), 2.55 W/cm2 (for 720 s), and 7.64 W/cm2 (for 80 s) the heat hypersensitivity was relieved the day following photobiomodulation (PBM) treatment by 37 ± 8.1% (statistically significant, p < 0.001), 26% ± 6% (p = 0.072), and 28 ± 6.1% (statistically significant, p = 0.032), respectively, and all three treatments reduced the hypersensitivity over the course of the experiment (13 days) at a statistically significant level (mixed-design analysis of variance, p < 0.05). The increases in tissue temperature (5.3 ± 1.0 and 1.3 ± 0.4°C from 33.3°C for the higher and lower power densities, respectively) at the neural target were well below those typically associated with permanent action potential disruption. CONCLUSIONS: The data from this study support the use of direct PBM on nerves of interest to reduce sensitivities associated with small-diameter fiber activity.

Paraspinal muscle fibre structural and contractile characteristics demonstrate distinct irregularities in patients with spinal degeneration and deformity.

BACKGROUND: Paraspinal and spinopelvic muscular dysfunction are hypothesized to be a causative factor for spinal degeneration and deformity; however, our fundamental understanding of paraspinal muscle (dys)function remains limited. METHODS: Twelve surgical patients with spinal degeneration were recruited and categorized into group DEG (four patients) with no sagittal imbalance and no usage of compensatory mechanisms; group DEG-COMP (four patients) with no sagittal imbalance through use of compensatory mechanisms; and group DEG-COMP-UNBAL (four patients) with sagittal imbalance despite use of compensatory mechanisms. From each patient, four biopsies were collected from right and left multifidus (MULT) and longissimus (LONG) for single fibre contractile and structural measurements. RESULTS: Eight of 48 (17%) biopsies did not exhibit any contractile properties. Specific force was not different between groups for the MULT (p = 0.47) but was greater in group DEG compared to group DEG-COMP-UNBAL for the LONG (p = 0.02). Force sarcomere-length properties were unusually variable both within and amongst patients in all groups. Thin filament (actin) lengths were in general shorter and more variable than published norms for human muscle. CONCLUSION: This study is the first to show a heightened intrinsic contractile muscle disorder (i.e. impaired specific force generation) in patients with spinal degeneration who are sagittally imbalanced (compared to patients without deformity). Additionally, there are clear indications that patients with spinal degeneration (all groups) have intrinsic force sarcomere-length properties that are dysregulated. This provides important insight into the pathophysiology of muscle weakness in this patient group.

Defining modern iatrogenic flatback syndrome: examination of segmental lordosis in short lumbar fusion patients undergoing thoracolumbar deformity correction.

PURPOSE: Understanding the mechanism and extent of preoperative deformity in revision procedures may provide data to prevent future failures in lumbar spinal fusion patients. METHODS: ASD patients without prior spine surgery (PRIMARY) and with prior short (SHORT) and long (LONG) fusions were included. SHORT patients were stratified into modes of failure: implant, junctional, malalignment, and neurologic. Baseline demographics, spinopelvic alignment, offset from alignment targets, and patient-reported outcome measures (PROMs) were compared across PRIMARY and SHORT cohorts. Segmental lordosis analyses, assessing under-, match, or over-correction to segmental and global lordosis targets, were performed by SRS-Schwab coronal curve type and construct length. RESULTS: Among 785 patients, 430 (55%) were PRIMARY and 355 (45%) were revisions. Revision procedures included 181 (23%) LONG and 174 (22%) SHORT corrections. SHORT modes of failure included 27% implant, 40% junctional, 73% malalignment, and/or 28% neurologic. SHORT patients were older, frailer, and had worse baseline deformity (PT, PI-LL, SVA) and PROMs (NRS, ODI, VR-12, SRS-22) compared to primary patients (p < 0.001). Segmental lordosis analysis identified 93%, 88%, and 62% undercorrected patients at LL, L1-L4, and L4-S1, respectively. SHORT patients more often underwent 3-column osteotomies (30% vs. 12%, p < 0.001) and had higher ISSG Surgical Invasiveness Score (87.8 vs. 78.3, p = 0.006). CONCLUSIONS: Nearly half of adult spinal deformity surgeries were revision fusions. Revision short fusions were associated with sagittal malalignment, often due to undercorrection of segmental lordosis goals, and frequently required more invasive procedures. Further initiatives to optimize alignment in lumbar fusions are needed to avoid costly and invasive deformity corrections. LEVEL OF EVIDENCE: IV: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Direct Photobiomodulation Therapy on the Sciatic Nerve Significantly Attenuates Acute Nociceptive Sensitivity Without Affecting Motor Output.

OBJECTIVES: Pharmacologic pain treatments lack specific targeting and often produce unwanted side effects (eg, addiction, additional hyperalgesia). We previously established that the direct application of laser irradiation (direct photobiomodulation [PBM]) of the sural nerve reduces thermal hypersensitivity in a rodent model of chronic pain, but not mechanical hypersensitivity. These observations were consistent with a selective reduction in the small-diameter fiber contribution to electrophysiologically measured evoked response after direct PBM of a sensory nerve (saphenous). However, to our knowledge, direct application of laser irradiation has never been performed in an animal model of acute nociceptive pain or on a mixed nerve in which sensory and motor outcomes can be observed. MATERIALS AND METHODS: In this study, we describe the effects of direct application of laser irradiation (808 nm, 60 mW, 4 minutes) on a mixed nerve (sciatic nerve) in an acute nociceptive pain model (intradermal capsaicin injection) in rats over the course of two weeks. To investigate whether laser irradiation of a mixed nerve alters motor function, in separate experiments, we applied laser irradiation to the sciatic nerve (using the same parameters as in the chronic pain experiments), and force generation of the gastrocnemius was measured. RESULTS: Capsaicin-induced hypersensitivities to mechanical (pin prick) and thermal (Hargreaves) noxious stimuli, associated with Aδ- and C-fibers, showed a maximal reduction of 70% and 56.2%, respectively, by direct PBM, when compared with a control group (vehicle injection, no PBM) on the same day. This reduction was determined to be significant using a mixed-design analysis of variance with a p value < 0.05. Force generation remained unchanged for up to 120 minutes after laser irradiation. In summary, direct PBM selectively inhibits C- and Aδ-fiber transmission while leaving Aɑ-, Aß-, and motor-fiber activity intact. CONCLUSIONS: These results, in conjunction with our previous analyses of laser irradiation effects on the sural nerve in a chronic spared nerve injury pain model, suggest that direct PBM is a promising candidate for treating pain induced by small-diameter fiber activity.

Surveying nonvisual arrestins reveals allosteric interactions between functional sites.

Arrestins are important scaffolding proteins that are expressed in all vertebrate animals. They regulate cell-signaling events upon binding to active G-protein coupled receptors (GPCR) and trigger endocytosis of active GPCRs. While many of the functional sites on arrestins have been characterized, the question of how these sites interact is unanswered. We used anisotropic network modeling (ANM) together with our covariance compliment techniques to survey all the available structures of the nonvisual arrestins to map how structural changes and protein-binding affect their structural dynamics. We found that activation and clathrin binding have a marked effect on arrestin dynamics, and that these dynamics changes are localized to a small number of distant functional sites. These sites include α-helix 1, the lariat loop, nuclear localization domain, and the C-domain ß-sheets on the C-loop side. Our techniques suggest that clathrin binding and/or GPCR activation of arrestin perturb the dynamics of these sites independent of structural changes.

Heroin- and Fentanyl-Induced Respiratory Depression in a Rat Plethysmography Model: Potency, Tolerance, and Sex Differences.

The opioid overdose death toll in the United States is an ongoing public health crisis. We characterized the magnitude and duration of respiratory depression, the leading cause of death in opioid overdose cases, induced by heroin or fentanyl and the development of tolerance in male and female rats. We used whole-body plethysmography to first establish dose-response curves by recording breathing for 60 minutes post-intravenous opioid injection. We then tested the development of respiratory tolerance to acute heroin or fentanyl over several weeks and to chronic fentanyl with acute fentanyl or heroin challenge. Heroin and fentanyl each provoked dose-dependent respiratory depression. Heroin caused prolonged (45-60 minute) respiratory depression in female and male rats, characterized by decreased frequency, tidal volume, and minute ventilation and increased inspiratory time and apneic pause. Fentanyl produced similar changes with a shorter duration (10-15 minutes). High-dose heroin or fentanyl produced robust respiratory depression that was slightly more severe in females and, when given intermittently (acute doses 2 to 3 weeks apart), did not lead to tolerance. In contrast, chronic fentanyl delivered with an osmotic minipump resulted in tolerance to acute fentanyl and heroin, characterized by a shorter duration of respiratory depression. This effect persisted during withdrawal in males only. Our model and experimental design will allow for investigation of the neurobiology of opioid-induced respiratory depression and for testing potential therapeutics to reverse respiratory depression or stimulate breathing. SIGNIFICANCE STATEMENT: Fentanyl was more potent and had shorter duration in producing respiratory depression than heroin in both sexes, whereas female rats were more sensitive than males to heroin-induced respiratory depression. Tolerance/cross-tolerance develops in chronic fentanyl administration but is minimized with long interadministration intervals.

The role of depressive symptoms and social support in the association of internet addiction with non-suicidal self-injury among adolescents: a cohort study in China.

BACKGROUND: Both internet addiction (IA) and non-suicidal self-injury (NSSI) are major public health concerns among adolescents, however, the association between IA and NSSI was not well understood. We aimed to investigate the association between IA and NSSI within a cohort study, and explore the mediated effect of depressive symptoms and the moderating effect of social support in the association. METHODS: A total of 1530 adolescents aged 11-14 years who completed both the baseline (T1) and 14-month follow-up (T2) survey of the Chinese Adolescent Health Growth Cohort were included for the current analysis. IA, NSSI, depressive symptoms and social support were measured at T1; depressive symptoms and NSSI were measured again at T2. Structural equation models were employed to estimate the mediated effect of depressive symptoms and the moderating effect of social support in the association between IA and NSSI at T2. RESULTS: IA was independently associated with an increased risk of NSSI at T2, with the total effect of 0.113 (95%CI 0.055-0.174). Depressive symptoms mediated the association between IA and NSSI at T2, and social support moderated the indirect but not the direct effect of IA on NSSI at T2. Sex differences were found on the mediated effect of depressive symptoms and the moderated mediation effect of social support. CONCLUSIONS: Interventions that target adolescents' NSSI who also struggle with IA may need to focus on reducing depressive symptoms and elevating social support.

Why Are Individuals Who Have Not Disclosed Self-Injury Comfortable Discussing Their Experiences in Research?

ABSTRACT: Not everyone who shares their lived experience of nonsuicidal self-injury (NSSI) in research has disclosed this previously outside of a research context. Our objective was to identify reasons people who have not previously disclosed their NSSI felt comfortable discussing their self-injury in research contexts. The sample consisted of 70 individuals with lived experience of self-injury who had not previously disclosed this experience outside of research (Mage = 23.04 years, SD = 5.90; 75.70% women). Using content analysis of open-ended responses, we identified three reasons participants felt comfortable discussing their NSSI in research. Most commonly, participants did not anticipate negative consequences discussing their NSSI due to the way the research was conducted (e.g., confidentiality). Second, participants valued NSSI research and wanted to contribute to such work. Third, participants referenced feeling mentally and emotionally prepared to discuss their NSSI. The findings indicate that individuals who have not previously disclosed their NSSI may wish to discuss their experience in research for a variety of reasons. Such findings highlight implications for how we foster safe spaces in research for people with lived experience of NSSI.

Further Silencing the Voiceless: The Role of Gatekeepers in Accessing Information About Self-Injury.

ABSTRACT: Gatekeepers play a pivotal role in protecting individuals under their care and are central to keeping people safe and away from harm. In the field of nonsuicidal self-injury (NSSI), a range of gatekeepers exist, including those who protect access to vulnerable research participants, those who protect school children, those charged with making decisions about funding priorities, and those in charge of clinical care for people who self-injure. The aim of this commentary is to outline the roles these different gatekeepers have in protecting access to research participants, access to NSSI knowledge, and access to clinical care for individuals who self-injure. We provide examples in which gatekeepers may present barriers and offer solutions for how to work with gatekeepers for mutual benefit.

Nd:YAG Laser Capsulotomy: Efficacy and Outcomes Performed by Optometrists.

SIGNIFICANCE: An increasing number of optometrists are performing Nd:YAG laser capsulotomy procedures; however, there is limited published information on the outcomes of these procedures. PURPOSE: This study aimed to assess the efficacy and safety of capsulotomy procedures performed by optometrists. METHODS: Subjects diagnosed with posterior capsule opacification causing reduced vision and subjective visual complaints were recruited for this study. A baseline examination was performed to ensure that the subjects met all the necessary criteria. The procedure was performed by a licensed doctor of optometry at six different clinics, and each subject was monitored for visual outcome and any potential complications. RESULTS: Subjects' Snellen visual acuity improved from an average of 20/40 to 20/23 ( P < .001) with no complications of increased intraocular pressure, inflammation, visually significant lens pitting, macular edema, or retinal detachment. Of 78 subjects who responded to a post-procedure survey, 77 (99%) reported subjective improvement in vision after capsulotomy. CONCLUSIONS: Based on the outcomes of this study, YAG laser capsulotomies are effective treatments to improve patient vision that can be safely and effectively performed by optometrists.

Surgical management of high-grade paediatric spondylolisthesis: meta-analysis and systematic review.

PURPOSE: There is currently no consensus on the management of high-grade spondylolisthesis (HGS) in paediatric populations. The objective of this analysis is to compare the outcomes of reduction followed by fusion (RFF) or in situ fusion (ISF) in paediatric patients. METHODS: Using major databases, a systematic literature search was performed. Primary studies comparing ISF with RFF in paediatric and adolescent patients were identified. Study data including patient-reported outcomes, complications, and spinopelvic parameters were collected and analysed. RESULTS: Seven studies were included, comprising 97 ISF and 131 RFF. Average patient age was 14.4 ± 2.1 years and follow up was 8.2 ± 5.1 years. Patients undergoing RFF compared to patients undergoing ISF alone were less likely to develop pseudarthrosis (RR 0.51, 95% CI, [0.26, 0.99], p = 0.05). On average, RFF led to 11.97º more reduction in slip angle and 34.8% more reduction in sagittal translation (p < 0.00001) compared to ISF. There was no significant difference between patient satisfaction and pain at follow up. Neurologic complications and reoperation rates were not significantly different. CONCLUSIONS: Both RFF and ISF are effective techniques for managing HGS. Performing a reduction followed by fusion reduces the likelihood of pseudarthrosis in paediatric patients. The difference between risk of neurologic complications, need for reoperation, patient satisfaction, and pain outcomes did not reach statistical significance. Correlation with patient-reported outcomes still needs to be further explored. LEVEL 3 EVIDENCE: Meta-analysis of Level 3 studies.

Comparison of major spine navigation platforms based on key performance metrics: a meta-analysis of 16,040 screws.

PURPOSE: The objective of this meta-analysis is to compare available computer-assisted navigation platforms by key performance metrics including pedicle screw placement accuracy, operative time, neurological complications, and blood loss. METHODS: A systematic review was conducted using major databases for articles comparing pedicle screw accuracy of computer-assisted navigation to conventional (freehand or fluoroscopy) controls via post-operative computed tomography. Outcome data were extracted and pooled by random-effects model for analysis. RESULTS: All navigation platforms demonstrated significant reduction in risk of breach, with Stryker demonstrating the highest accuracy compared to controls (OR 0.16 95% CI 0.06 to 0.41, P < 0.00001, I2 = 0%) followed by Medtronic. There were no significant differences in accuracy or most surgical outcome measures between platforms; however, BrainLab demonstrated significantly faster operative time compared to Medtronic by 30 min (95% CI - 63.27 to - 2.47, P = 0.03, I2 = 74%). Together, there was significantly lower risk of major breach in the navigation group compared to controls (OR 0.42, 95% CI 0.27-0.63, P < 0.0001, I2 = 56%). CONCLUSIONS: When comparing between platforms, Stryker demonstrated the highest accuracy, and Brainlab the shortest operative time, both followed by Medtronic. No significant difference was found between platforms regarding neurologic complications or blood loss. Overall, our results demonstrated a 60% reduction in risk of major breach utilizing computer-assisted navigation, coinciding with previous studies, and supporting its validity. This study is the first to directly compare available navigation platforms offering insight for further investigation and aiding in the institutional procurement of platforms. LEVEL 3 EVIDENCE: Meta-analysis of Level 3 studies.

Hospital spending and length of stay attributable to perioperative adverse events for inpatient hip, knee, and spine surgery: a retrospective cohort study.

BACKGROUND: The incremental hospital cost and length of stay (LOS) associated with adverse events (AEs) has not been well characterized for planned and unplanned inpatient spine, hip, and knee surgeries. METHODS: Retrospective cohort study of hip, knee, and spine surgeries at an academic hospital in 2011-2012. Adverse events were prospectively collected for 3,063 inpatient cases using the Orthopaedic Surgical AdVerse Event Severity (OrthoSAVES) reporting tool. Case costs were retrospectively obtained and inflated to equivalent 2021 CAD values. Propensity score methodology was used to assess the cost and LOS attributable to AEs, controlling for a variety of patient and procedure factors. RESULTS: The sample was 55% female and average age was 64; 79% of admissions were planned. 30% of cases had one or more AEs (82% had low-severity AEs at worst). The incremental cost and LOS attributable to AEs were $8,500 (95% confidence interval [CI]: 5100-11,800) and 4.7 days (95% CI: 3.4-5.9) per admission. This corresponded to a cumulative $7.8 M (14% of total cohort cost) and 4,290 bed-days (19% of cohort bed-days) attributable to AEs. Incremental estimates varied substantially by (1) admission type (planned: $4,700/2.4 days; unplanned: $20,700/11.5 days), (2) AE severity (low: $4,000/3.1 days; high: $29,500/11.9 days), and (3) anatomical region (spine: $19,800/9 days; hip: $4,900/3.8 days; knee: $1,900/1.5 days). Despite only 21% of admissions being unplanned, adverse events in these admissions cumulatively accounted for 59% of costs and 62% of bed-days attributable to AEs. CONCLUSIONS: This study comprehensively demonstrates the considerable cost and LOS attributable to AEs in orthopaedic and spine admissions. In particular, the incremental cost and LOS attributable to AEs per admission were almost five times as high among unplanned admissions compared to planned admissions. Mitigation strategies focused on unplanned surgeries may result in significant quality improvement and cost savings in the healthcare system.

What is important to the decision to disclose nonsuicidal self-injury in formal and social contexts?

OBJECTIVE: Disclosure of nonsuicidal self-injury (NSSI) is associated with a range of both positive (e.g., help-seeking) and negative (e.g., discrimination) outcomes. The aim of this study was to assess the importance of a range of factors concerned with: NSSI experiences, self-efficacy to disclose self-injury, interpersonal factors, and reasons for or expectations of disclosure, to the decision to disclose self-injury to friends, family members, significant others, and health professionals. METHODS: Three hundred seventy-one participants with lived experience of NSSI completed a survey in which they rated the importance of the aforementioned factors to the decision of whether to disclose NSSI to different people. A mixed-model analysis of variance was conducted to investigate whether the factors differed in importance and if this importance differed across relationship types. RESULTS: All factors held importance, though to differing degrees, with those related to relationship quality being most important overall. Generally, factors relating to tangible aid were considered more important when considering disclosure to health professionals than to other people. Conversely, interpersonal factors, particularly trust, were more important when disclosing to individuals in social or personal relationships. CONCLUSION: The findings provide preliminary insight into how different considerations may be prioritized when navigating NSSI disclosure, in a way that may be tailored to different contexts. For clinicians, the findings highlight that clients may expect tangible forms of support and nonjudgment in the event that they disclose their self-injury in this formal setting.

Differential immunostaining patterns of transient receptor potential (TRP) ion channels in the rat nodose ganglion.

Vagal afferents regulate numerous physiological functions including arterial blood pressure, heart rate, breathing, and nociception. Cell bodies of vagal afferents reside in the inferior vagal (nodose) ganglia and their stimulation by various means is being considered as a way to regulate cardiorespiratory responses and control pain sensations. Stimulation of the nodose by exposure to infrared light is recently being considered as a precise way to elicit responses. These responses would likely involve the activity of temperature-sensitive membrane-bound channels. While papers have been published to track the expression of these transient receptor potential ion channels (TRPs), further studies are warranted to determine the in situ expression of the endogenous TRP proteins in the nodose ganglia to fully understand their pattern of expression, subcellular locations, and functions in this animal model. TRP ion channels are a superfamily of Na+ /Ca2+ -channels whose members are temperature- and/or mechano-sensitive and therefore represent a potential set of proteins that will be activated directly or indirectly by infrared light. Here, we report the spatial localization of six TRP channels, TRPV1, TRPV4, TRPM3, TRPM8, TRPA1, and TRPC1, from nodose ganglia taken from juvenile male Sprague-Dawley rats. The channels were detected using immunohistology with fluorescent tags on cryosections and imaged using confocal microscopy. All six TRP channels were detected with different levels of intensity in neuronal cell bodies and some were also detected in axonal fibers and blood vessels. The TRP receptors differed in their prevalence, in their patterns of expression, and in subcellular expression/localization. More specifically, TRPV1, TRPV4, TRPA1, TRPM8, TRPC1, and TRPM3 were found in vagal afferent cell bodies with a wide range of immunostaining intensity from neuron to neuron. Immunostaining for TRPV1, TRPV4, and TRPA1 appeared as fine particles scattered throughout the cytoplasm of the cell body. Intense TRPV1 immunostaining was also evident in a subset of axonal fibers. TRPM8 and TRPC1 were expressed in courser particles suggesting different subcellular compartments than for TRPV1. The localization of TRPM3 differed markedly from the other TRP channels with an immunostaining pattern that was localized to the periphery of a subset of cell bodies, whereas a scattering or no immunostaining was detected within the bulk of the cytoplasm. TRPV4 and TRPC1 were also expressed on the walls of blood vessels. The finding that all six TRP channels (representing four subfamilies) were present in the nodose ganglia provides the basis for studies designed to understand the roles of these channels in sensory transmission within vagal afferent fibers and in the responses elicited by exposure of nodose ganglia to infrared light and other stimuli. Depending on the location and functionality of the TRP channels, they may regulate the flux of Na+ /Ca2+ -across the membranes of cell bodies and axons of sensory afferents, efferent (motor) fibers coursing through the ganglia, and in vascular smooth muscle.

Haploinsufficient tumor suppressor PRP4K is negatively regulated during epithelial-to-mesenchymal transition.

The pre-mRNA processing factor 4 kinase (PRP4K, also known as PRPF4B) is an essential gene. However, reduced PRP4K expression is associated with aggressive breast and ovarian cancer phenotypes including taxane therapy resistance, increased cell migration and invasion in vitro, and cancer metastasis in mice. These results are consistent with PRP4K being a haploinsufficient tumor suppressor. Increased cell migration and invasion is associated with epithelial-to-mesenchymal transition (EMT), but how reduced PRP4K levels affect normal epithelial cell migration or EMT has not been studied. Depletion of PRP4K by small hairpin RNA (shRNA) in non-transformed mammary epithelial cell lines (MCF10A, HMLE) reduced or had no effect on 2D migration in the scratch assay but resulted in greater invasive potential in 3D transwell assays. Depletion of PRP4K in mesenchymal triple-negative breast cancer cells (MDA-MB-231) resulted in both enhanced 2D migration and 3D invasion, with 3D invasion correlated with higher fibronectin levels in both MDA-MB-231 and MCF10A cells and without changes in E-cadherin. Induction of EMT in MCF10A cells, by treatment with WNT-5a and TGF-ß1, or depletion of eukaryotic translation initiation factor 3e (eIF3e) by shRNA, resulted in significantly reduced PRP4K expression. Mechanistically, induction of EMT by WNT-5a/TGF-ß1 reduced PRP4K transcript levels, whereas eIF3e depletion led to reduced PRP4K translation. Finally, reduced PRP4K levels after eIF3e depletion correlated with increased YAP activity and nuclear localization, both of which are reversed by overexpression of exogenous PRP4K. Thus, PRP4K is a haploinsufficient tumor suppressor negatively regulated by EMT, that when depleted in normal mammary cells can increase cell invasion without inducing full EMT.

Demographic partitioning of dynamic energy subsidies revealed with an Ornstein-Uhlenbeck space use model.

In populations across many taxa, a large fraction of sexually mature individuals do not breed but are attempting to enter the breeding population. Such individuals, often referred to as "floaters," can play critical roles in the dynamics and stability of these populations and buffer them through periods of high adult mortality. Floaters are difficult to study, however, so we lack data needed to understand their roles in the population ecology and conservation status of many species. Here, we analyzed satellite telemetry data with a newly developed mechanistic space use model based on an Ornstein-Uhlenbeck process to help overcome the paucity of data in studying the differential habitat selection and space use of floater and territorial golden eagles Aquila chrysaetos. Our sample consisted of 49 individuals tracked over complete breeding seasons across 4 years, totaling 104 eagle breeding seasons. Modeling these data mechanistically was required to disentangle key differences in movement and particularly to separate aspects of movement driven by resource selection from those driven by use of a central place. We found that floaters generally had more expansive space use patterns and larger home ranges, as well as evidence that they partition space with territorial individuals seemingly on fine scales through differential habitat and resource selection. Floater and territorial eagle home ranges overlapped markedly, suggesting that floaters use the interstices between territories. Furthermore, floater and territorial eagles differed in how they selected for uplift variables, key components of soaring birds' energy landscape, with territorial eagles apparently better able to find and use thermal uplift. We also found relatively low individual heterogeneity in resource selection, especially among territorial individuals, suggesting a narrow realized niche for breeding individuals, which varied from the level of among-individual variation present during migration. This work furthers our understanding of floaters' potential roles in the population ecology of territorial species and suggests that conserving landscapes occupied by territorial eagles also protects floaters.

Support Seeking in the Context of Self-Injury Recovery: Perspectives From Individuals With Lived Experience.

ABSTRACT: A sample of 229 university students responded to open-ended questions for the present study, which aimed to gain a deeper understanding of lived experiences of support seeking in the context of self-injury recovery. Inductive thematic analysis of the responses indicated themes from two domains: the benefits of support seeking and the barriers to support seeking. The first domain highlighted benefits from both professional sources (such as receiving diagnosis and referrals to therapy, learning emotion regulation strategies, and developing an improved understanding of self) and informal sources (such as receiving tangible aid, having a support system, and having a compassionate space). The second domain indicated that barriers could be both intrapersonal (such as desire to continue nonsuicidal self-injury, embarrassment and shame, establishing agency without others' support, and minimizing self-injury) and interpersonal (such as fear of being stigmatized, concern for others, and unhelpful prior experiences) in nature. Implications for future research, outreach efforts, and clinical practice are discussed.