Self-help groups and opioid use disorder treatment: An investigation using a machine learning-assisted robust causal inference framework.

OBJECTIVES: This study investigates the impact of participation in self-help groups on treatment completion among individuals undergoing medication for opioid use disorder (MOUD) treatment. Given the suboptimal adherence and retention rates for MOUD, this research seeks to examine the association between treatment completion and patient-level factors. Specifically, we evaluated the causal relationship between self-help group participation and treatment completion for patients undergoing MOUD. METHODS: We used the Substance Abuse and Mental Health Services Administration's (SAMHSA) Treatment Episode Data Set: Discharges (TEDS-D) from 2015 to 2019. The data are filtered by the patient's opioid use history, demographics, treatment modality, and other relevant information. In this observational study, machine learning models (Lasso Regression, Decision Trees, Random Forest, and XGBoost) were developed to predict treatment completion. Outcome Adaptive Elastic Net (OAENet) was used to select confounders and outcome predictors, and the robust McNemars test was used to evaluate the causal relationship between self-help group participation and MOUD treatment completion. RESULTS: The machine-learning models showed a strong association between participation in self-help groups and treatment completion. Our causal analysis demonstrated an average treatment effect on treated (ATT) of 0.260 and a p-value < 0.0001 for the robust McNemars test. CONCLUSIONS: Our study demonstrates the importance of participation in self-help groups for MOUD treatment recipients. We found that participation in MOUD along with self-help groups caused higher chances of treatment completion than MOUD alone. This suggests that policymakers should consider further integrating self-help groups into the treatment for OUD to improve the adherence and completion rate.

Size onset of metallic behavior in neutral aluminum clusters.

The excited state lifetimes of neutral (Al)n clusters up to ∼1 nm in diameter in size, where n ≤ 43, are systematically measured with femtosecond time-resolved mass spectrometry. The onset of metallic behavior is identified as a distinct change in the relaxation behavior initiated with single ultraviolet (400 nm) photon excitation. The experimentally measured excited state lifetimes gradually decrease with size for small molecular scale clusters (n < 10) before becoming indistinguishable for larger clusters (n > 9), where the measurements are comparable to electron-lattice relaxation time of bulk Al (∼300 fs). Particularly intense, or magic, Aln clusters do not exhibit any significant excited state lifetime behavior. Time-dependent density functional theory quantify the excited state properties and are presented to show that dynamics are strongly tied to the excited state charge carrier distributions and overlap, rather than detailed changes related to changes in the cluster's electronic and geometric structure. The consistency in excited state lifetimes for clusters larger than n = 9 is attributed to the hybridization of the s- and p-orbitals as well as increasing delocalization. Al3 exhibits unique temporal delay in its transient behavior that is attributed to a transition from triangular ground state to linear structure upon excitation.

Tracing sources of inorganic suspended particulate matter in the Great Barrier Reef lagoon, Australia.

Water clarity on the inshore Great Barrier Reef (GBR) is greatly influenced by terrestrial runoff of suspended particulate matter (SPM). Catchment sediment tracing studies often do not extend into the marine environment, preventing the analysis of preferential marine transport. This study employs novel collection and sediment tracing techniques to examine the transport of the terrigenous 'mineral' component of plume SPM within the GBR lagoon for two flood events. Utilising geochemical, radionuclide and clay mineral analysis, we trace terrigenous mineral sediments > 100 km from the river mouth. We show that the SPM geochemistry is highly influenced by particle-size fractionation, desorption, and dilution within the plume, rendering traditional tracing methods unviable. However, the ratios of rare earth elements (REE) to thorium (Th) provide stable tracers of mineral SPM transported across the catchment to marine continuum and allow the identification of discrete catchment sources for each flood event. Plume sediment radionuclides are also stable and consistent with sub-surface erosion sources.

A practical approach to supported liquid extraction and measurement of 18 steroids in plasma and serum by targeted liquid chromatography tandem mass spectrometry.

Chromatography combined with mass spectrometry is a gold standard technique for steroid measurement, however the type of sample preparation, the dynamic range and reliability of the calibration curve, the chromatographic separation and mass spectrometry settings ultimately determine the success of the method. The steroid biosynthetic pathway is conserved in higher mammals and literature demonstrates that the concentration ranges of different steroid groups are relatively comparable across species. We sought to develop a robust and reliable multi steroid targeted analysis method for blood that would have wide application across higher mammals. The method was developed following bioanalytical method validation guidelines to standards typically applied to human clinical studies, including isotopically labelled internal standards where at all possible. Here we describe the practical approach to a 96-well supported liquid extraction (SLE) method of extraction from plasma (200 µL) using an Extrahera liquid handling robot (Biotage, Sweden), including quality control samples, followed by a comprehensive separation and targeted LC-MS/MS analysis of 18 steroids in plasma (pregnenolone, progesterone, 17α-hydroxyprogesterone, 11-deoxycorticosterone, corticosterone, 11-dehydrocorticosterone, aldosterone, 11-deoxycortisol, 21-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, 5α-dihydrotestosterone, dehydroepiandrosterone, estrone, 17ß-estradiol and estriol). •SLE in a 96-well format of up to 74 biological plasma samples, enriched with multiple isotopically labelled internal standards, a 12-point aqueous calibration curve, and 6 serum quality controls, designed to monitor long-term performance of the method•Chromatographic separation of multiple steroids along the gradient, with ammonium fluoride mobile phase additive to improve sensitivity, followed by electrospray ionisation and constant polarity switching•Aqueous calibration standards that cover physiologically relevant ranges - high nanomolar glucocorticoids, low nanomolar androgens and picomolar ranges for estrogens and steroid intermediates.

Identification and measurement of intensive economic growth in a Roman imperial province.

A key question in economic history is the degree to which preindustrial economies could generate sustained increases in per capita productivity. Previous studies suggest that, in many preindustrial contexts, growth was primarily a consequence of agglomeration. Here, we examine evidence for three different socioeconomic rates that are available from the archaeological record for Roman Britain. We find that all three measures show increasing returns to scale with settlement population, with a common elasticity that is consistent with the expectation from settlement scaling theory. We also identify a pattern of increase in baseline rates, similar to that observed in contemporary societies, suggesting that this economy did generate modest levels of per capita productivity growth over a four-century period. Last, we suggest that the observed growth is attributable to changes in transportation costs and to institutions and technologies related to socioeconomic interchange. These findings reinforce the view that differences between ancient and contemporary economies are more a matter of degree than kind.

Disruption of intestinal oxygen balance in acute colitis alters the gut microbiome.

The juxtaposition of well-oxygenated intestinal colonic tissue with an anerobic luminal environment supports a fundamentally important relationship that is altered in the setting of intestinal injury, a process likely to be relevant to diseases such as inflammatory bowel disease. Herein, using two-color phosphorometry to non-invasively quantify both intestinal tissue and luminal oxygenation in real time, we show that intestinal injury induced by DSS colitis reduces intestinal tissue oxygenation in a spatially defined manner and increases the flux of oxygen from the tissue into the gut lumen. By characterizing the composition of the microbiome in both DSS colitis-affected gut and in a bioreactor containing a stable human fecal community exposed to microaerobic conditions, we provide evidence that the increased flux of oxygen into the gut lumen augments glycan degrading bacterial taxa rich in glycoside hydrolases which are known to inhabit gut mucosal surface. Continued disruption of the intestinal mucus barrier through such a mechanism may play a role in the perpetuation of the intestinal inflammatory process.

Patient experiences with telehealth treatment for opioid use disorder in Alabama.

INTRODUCTION: Telehealth-only provision of buprenorphine for the treatment of opioid use disorder (OUD) was first made possible during the COVID-19 pandemic. However, Alabama instituted a law in July 2022 that mandated an annual in-person visit in order to receive this treatment. In July 2023, our usually telehealth-only group established a temporary clinic in Birmingham to meet this requirement. METHODS: The study administered a survey instrument to patients at the time of clinic check-in. RESULTS: 158 of 160 (98.8 %) patients completed the survey. Mean distance traveled was 86.4 (standard deviation (SD) 53.7) miles; time required for travel was mean 1.6 (SD 1.0) hours. Twenty-five patients (15.8 %) reported needing to find childcare to attend the visit and 40 patients (25.3 %) reported missing work to attend. Patients disagreed (median 2 on 1-5 Likert scale, interquartile range (IQR) <1-3>) that it is important to see their provider in-person, that seeing their provider in-person improves care or improves their ability to succeed in treatment, and that they have other OUD treatment resources in their community. Patients strongly agreed (median 5, IQR <5-5>) that OUD can be treated by telehealth without the need for an in-person visit. CONCLUSIONS: An annual in-person visits requirement to receive telehealth OUD services imposed a significant burden on patients, was not desired by patients, and may be associated with harm.

Profiles of trauma exposure type and their associations to pain-related outcomes among adults with chronic pain: A two-year longitudinal study.

Individuals with chronic pain report disproportionally higher rates of trauma; yet, it is unclear whether different types of trauma (e.g., sexual, accidental trauma) are associated with worse pain outcomes. The present study sought to: 1) identify subgroups of people with chronic pain based on trauma type; and 2) determine whether subgroups differ in terms of pain characteristics over a two-year period. Individuals with chronic pain (N = 1,451) participated in an online study and completed self-report questionnaires at baseline, 3-, 12- and 24-month follow-up. Trauma was assessed via the Life Events Checklist for DSM-5. Pain intensity and interference were measured via the Brief Pain Inventory and pain distribution was evaluated using the Widespread Pain Index. Latent class analyses produced a three-class solution consisting of individuals with high and diverse trauma (16.3%), high sexual trauma (18.4%), and low/accidental trauma (57.1%) with the rest of the sample endorsing no trauma history (8.2%). After controlling for key demographic variables and baseline outcome levels, individuals in the high and diverse trauma group endorsed higher levels of pain severity and interference at the 3 and 12-month follow-ups compared to the group with no trauma (p<.01). Additionally, relative to the no trauma group, individuals in the high sexual trauma group reported higher levels of pain interference and more widespread pain at the 3-month follow-up (p<.05). Findings underscore the importance of screening for trauma and suggest that the type and variety of trauma experienced may be relevant to pain-related outcomes. PERSPECTIVE: This article highlights how an individual's unique trauma history may be related to their current pain experience. Knowledge of the type and frequency of past trauma may have relevant clinical implications for the treatment of chronic pain.

The Role of CyberKnife Stereotactic Radiosurgery in Recurrent Cranial Medulloblastomas across Pediatric and Adult Populations.

Background/Objectives: Medulloblastoma is the most common malignant brain tumor in children. In recent decades, the therapeutic landscape has undergone significant changes, with stereotactic radiosurgery (SRS) emerging as a promising treatment for recurrent cases. Our study provides a comprehensive analysis of the long-term efficacy and safety of SRS in recurrent medulloblastomas across both pediatric and adult patients at a single institution. Methods: We retrospectively reviewed the clinical and radiological records of patients who underwent CyberKnife SRS for recurrent cranial medulloblastomas at our institution between 1998 and 2023. Follow-up data were available for 15 medulloblastomas in 10 patients. The cohort comprised eight pediatric patients (ages 3-18) and two adult patients (ages 19-75). The median age at the time of SRS was 13 years, the median tumor volume accounted for 1.9 cc, the median biologically equivalent dose (BED) was 126 Gy, and the single-fraction equivalent dose (SFED) was 18 Gy. The SRS was administered at 75% of the median isodose line. Results: Following a median follow-up of 39 months (range: 6-78), 53.3% of the medulloblastomas progressed, 13.3% regressed, and 33.3% remained stable. The 3-year local tumor control (LTC) rate for all medulloblastomas was 65%, with lower rates observed in the adult cohort (50%) and higher rates in pediatric patients (67%). The 3-year overall survival (OS) rate was 70%, with significantly higher rates in pediatric patients (75%) compared to adult patients (50%). The 3-year progression-free survival (PFS) rate was 58.3%, with higher rates in pediatric patients (60%) compared to adult patients (50%). Two pediatric patients developed radiation-induced edema, while two adult patients experienced radiation necrosis at the latest follow-up, with both adult patients passing away. Conclusions: Our study provides a complex perspective on the efficacy and safety of CyberKnife SRS in treating recurrent cranial medulloblastomas across pediatric and adult populations. The rarity of adverse radiation events (AREs) underscores the safety profile of SRS, reinforcing its role in enhancing treatment outcomes. The intricacies of symptomatic outcomes, intertwined with factors such as age, tumor location, and prior surgeries, emphasize the need for personalized treatment approaches. Our findings underscore the imperative for ongoing research and the development of more refined treatment strategies for recurrent medulloblastomas. Given the observed disparities in treatment outcomes, a more meticulous tailoring of treatment approaches becomes crucial.

Puberty classifications in beef heifers are moderately to highly heritable and associated with candidate genes related to cyclicity and timing of puberty.

Introduction: Pubertal attainment is critical to reproductive longevity in heifers. Previously, four heifer pubertal classifications were identified according to attainment of blood plasma progesterone concentrations > 1 ng/ml: 1) Early; 2) Typical; 3) Start-Stop; and 4) Non-Cycling. Early and Typical heifers initiated and maintained cyclicity, Start-Stop started and then stopped cyclicity and Non-Cycling never initiated cyclicity. Start-Stop heifers segregated into Start-Stop-Discontinuous (SSD) or Start-Stop-Start (SSS), with SSD having similar phenotypes to Non-Cycling and SSS to Typical heifers. We hypothesized that these pubertal classifications are heritable, and loci associated with pubertal classifications could be identified by genome wide association studies (GWAS). Methods: Heifers (n = 532; 2017 - 2022) genotyped on the Illumina Bovine SNP50 v2 or GGP Bovine 100K SNP panels were used for variant component estimation and GWAS. Heritability was estimated using a univariate Bayesian animal model. Results: When considering pubertal classifications: Early, Typical, SSS, SSD, and Non-Cycling, pubertal class was moderately heritable (0.38 ± 0.08). However, when heifers who initiated and maintained cyclicity were compared to those that did not cycle (Early+Typical vs. SSD+Non-Cycling) heritability was greater (0.59 ± 0.19). A GWAS did not identify single nucleotide polymorphisms (SNPs) significantly associated with pubertal classifications, indicating puberty is a polygenic trait. A candidate gene approach was used, which fitted SNPs within or nearby a set of 71 candidate genes previously associated with puberty, PCOS, cyclicity, regulation of hormone secretion, signal transduction, and methylation. Eight genes/regions were associated with pubertal classifications, and twenty-two genes/regions were associated with whether puberty was attained during the trial. Additionally, whole genome sequencing (WGS) data on 33 heifers were aligned to the reference genome (ARS-UCD1.2) to identify variants in FSHR, a gene critical to pubertal attainment. Fisher's exact test determined if FSHR SNPs segregated by pubertal classification. Two FSHR SNPs that were not on the bovine SNP panel were selected for additional genotyping and analysis, and one was associated with pubertal classifications and whether they cycled during the trial. Discussion: In summary, these pubertal classifications are moderately to highly heritable and polygenic. Consequently, genomic tools to inform selection/management of replacement heifers would be useful if informed by SNPs associated with cyclicity and early pubertal attainment.

A review of prospective studies regarding percutaneous peripheral nerve stimulation treatment in the management of chronic pain.

Conventionally, peripheral nerve stimulation (PNS) for treatment of chronic pain has involved a two-stage process: a short-term (e.g., 7 days) trial and, if significant pain relief is achieved, a permanent PNS system is implanted. A percutaneous PNS treatment is now available where a coiled lead may be implanted for up to 60 days with the goal of producing sustained relief. In the present review, published prospective trials using percutaneous PNS treatment were identified and synthesized. The collected evidence indicates that percutaneous PNS treatment for up to 60 days provides durable clinically significant improvements in pain and pain interference. Similar efficacy across diverse targets and etiologies supports the broad applicability for use within the chronic pain population using this nonopioid technology.

What is this review about? This review looks at a drug-free way to treat chronic pain called percutaneous peripheral nerve stimulation (PNS). Percutaneous means it is placed through the skin. PNS applies small amounts of electricity to the nerves to reduce chronic pain. Most PNS systems involve a two-step process. A short trial is first performed to see if a patient has pain relief. A permanent system is then placed if the person had pain relief. Percutaneous PNS treatments are different. They use a thin wire called a lead placed in the body for up to 60 days. The lead is taken out at the end of the treatment period. Studies have shown that this type of PNS treatment can reduce chronic pain even after the treatment is over. No previous article has collected all these studies of percutaneous PNS in one place.What evidence was gathered? This review found evidence from studies on treatment of chronic pain. Pain types included shoulder pain, neuropathic pain and low back pain. It found that percutaneous PNS treatment for up to 60 days can reduce pain and how pain interferes with daily life.How can these data lead to better care for patients? These findings mean that percutaneous PNS treatments could be a useful, non-drug option for many types of chronic pain.

The effectiveness of cognitive behavioral therapy for insomnia on sleep outcomes in the context of pain among older adult veterans.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) is the gold-standard treatment for insomnia disorder in adults. Compared to young adults, older adults have increased risk for the development of conditions associated with chronic pain, which may impact the efficacy of CBT-I in improving insomnia symptoms in older adults. This study evaluated the effect of participant-rated pain on sleep-related outcomes of a supervised, non-clinician administered CBT-I program in older adult patients with chronic insomnia disorder. METHODS: Secondary analysis was conducted using data from a randomized controlled trial among 106 community-dwelling older adult veterans (N = 106; mean age 72.1 years, 96% male, 78.3% White, 6.6% Hispanic, 5.7% African American) with chronic (≥3 months) insomnia disorder. Participants engaged in five sessions of manual-based CBT-I in individual or group format within one Department of Veterans Affairs healthcare system, provided by non-clinician "sleep coaches" who had weekly telephone supervision by behavioral sleep medicine specialists. Insomnia symptoms (Insomnia Severity Index), perceived sleep quality (Pittsburgh Sleep Quality Index), fatigue (Flinder's Fatigue Scale), daytime sleepiness (Epworth Sleepiness Scale), and perceived pain severity (items from the Geriatric Pain Measure) were assessed at 4 time points: baseline, one-week posttreatment, 6-month follow-up, and 12-month follow-up. Mixed effects models with time invariant and time varying predictors were employed for analyses. RESULTS: CBT-I improved insomnia symptoms, perceived sleep quality, fatigue, and daytime sleepiness among older veterans with chronic insomnia. Participant-reported pain was associated with greater improvements in insomnia symptoms following CBT-I. Pain did not affect improvements in other sleep-related outcomes (-0.38 ≤ b ≤ 0.07, p > 0.05). Between-subjects differences in pain, but not within-subject changes in pain over time, appeared to play a central role in insomnia symptom improvement at posttreatment, with individuals with higher-than-average pain showing greater insomnia symptom improvement (ISI score reduction; -0.32 ≤ b ≤ -0.28, p ≤ 0.005). CONCLUSIONS: Pain did not meaningfully hinder the effects of CBT-I on sleep outcomes. Among older veterans with chronic insomnia disorder, individuals with higher pain exhibited slightly greater improvement in insomnia than those with lower levels of pain. These findings suggest that experiencing pain does not impair treatment response and should not preclude older adults with insomnia from being offered CBT-I.

Primary Stereotactic Body Radiotherapy for Spinal Bone Metastases From Lung Adenocarcinoma.

OBJECTIVE: This study aimed to assess the results of primary stereotactic body radiotherapy (SBRT) for spinal bone metastases (SBM) originating from lung adenocarcinoma (ADC). We considered the revised Tokuhashi score (rTS), Spinal Instability Neoplastic Score (SINS), and genetic characteristics. METHODS: We examined adult patients with lung ADC who underwent primary SBRT (using the CyberKnife System) for SBM between March 2012 and January 2023. RESULTS: We analyzed data from 99 patients, covering 152 SBM across 194 vertebrae. The overall local control (LC) rate was 77.6% for SBM from lung ADC, with a LC rate of 90.7% at 1 year. The median period for local progression (LP) occurrence was recorded at 10.0 (3-52) months. Additionally, Asian patients demonstrated higher LC rates than White patients. Utilizing the rTS and SINS as predictive tools, we revealed that a poor survival prognosis and an unstable spinal structure were associated with increased rates of LP. Furthermore, the presence of osteolytic bone destructions and pain complaints were significantly correlated with the occurrence of LP. In the cohort of this study, 108 SBM underwent analysis to determine the expression levels of programmed cell death ligand 1 (PD-L1). Additionally, within this group, 60 showed mutations in the epidermal growth factor receptor (EGFR) alongside PD-L1 expression. Nevertheless, these genetic differences did not result in statistically significant differences in the LC rate. CONCLUSION: The one-year LC rate for primary SBRT targeting SBM from lung ADC stood at 90.7%, particularly with the use of the CyberKnife System. Patients achieving LC exhibited significantly longer survival times compared to those with LP.

Corrigendum to "Androgen Deprivation and Radiotherapy with or Without Docetaxel for Localized High-risk Prostat Cancer: Long-term Follow-up from the Randomized NRG Oncology RTOG 0521 Trial" [Eur. Eurol. 84(2) (2023) 156-163].

BACKGROUND: Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer. OBJECTIVE: To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT. DESIGN, SETTING, AND PARTICIPANTS: High-risk localized prostate cancer patients (>50% of patients had Gleason 9-10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel. A total of 612 patients were accrued, and 563 were eligible and included in the modified intent-to-treat analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was overall survival (OS). Analyses with Cox proportional hazards were performed as prespecified in the protocol; however, there was evidence of nonproportional hazards. Thus, a post hoc analysis was performed using the restricted mean survival time (RMST). The secondary endpoints included biochemical failure, distant metastasis (DM) as detected by conventional imaging, and disease-free survival (DFS). RESULTS AND LIMITATIONS: After 10.4 yr of median follow-up among survivors, the hazard ratio (HR) for OS was 0.89 (90% confidence interval [CI] 0.70-1.14; one-sided log-rank p = 0.22). Survival at 10 yr was 64% for ADT + EBRT and 69% for ADT + EBRT + docetaxel. The RMST at 12 yr was 0.45 yr and not statistically significant (one-sided p = 0.053). No differences were detected in the incidence of DFS (HR = 0.92, 95% CI 0.73-1.14), DM (HR = 0.84, 95% CI 0.73-1.14), or prostate-specific antigen recurrence risk (HR = 0.97, 95% CI 0.74-1.29). Two patients had grade 5 toxicity in the chemotherapy arm and zero patients in the control arm. CONCLUSIONS: After a median follow-up of 10.4 yr among surviving patients, no significant differences are observed in clinical outcomes between the experimental and control arms. These data suggest that docetaxel should not be used for high-risk localized prostate cancer. Additional research may be warranted using novel predictive biomarkers. PATIENT SUMMARY: No significant differences in survival were noted after long-term follow-up for high-risk localized prostate cancer patients in a large prospective trial where patients were treated with androgen deprivation therapy + radiation to the prostate ± docetaxel.

TiO2 nanoparticle photoactivation and oxidation reactions in freshwater and marine systems: The role of radical scavengers.

Titanium dioxide nanoparticles (TiO2-NP) present in wastewater effluent are discharged into freshwater and saltwater (i.e., marine) systems. TiO2-NP can be solar-driven photoactivated by ultraviolet (UV)-light producing reactive oxygen species including hydroxyl radicals (·OH). ·OH are non-selective and react with a broad range of species in water. In other studies, photoactivation of TiO2-NP has been correlated with oxidative stress and ecotoxicological impacts on plant and animal biota. This study examined the photoactivation of TiO2-NP in freshwater and saltwater systems, and contrasted the oxidation potential in both systems using methylene blue (MB) as a reaction probe. Maximum MB loss (51.9%, n = 4; 95% confidence interval 49.4-54.5) was measured in salt-free, deionized water where ·OH scavenging was negligible; minimum MB loss (1%) was measured in saltwater due to significant ·OH scavenging, indicating the inverse correlation between MB loss and radical scavenging. A kinetic analysis of scavenging by seawater constituents indicated Cl- had the greatest impact due to high concentration and high reaction rate constant. Significant loss of MB occurred in the presence of Br- relative to other less aggressive scavengers present in seawater (i.e., HCO3-, HSO4-). This result is consistent with the formation of Bromate, a strong oxidant that subsequently reacts with MB. In freshwater samples collected from different water bodies in Oklahoma (n = 12), the average MB loss was 13.4%. Greater MB loss in freshwater systems relative to marine systems was due to lower ·OH scavenging by various water quality parameters. Overall, TiO2-NP photoactivation in freshwater systems has the potential to cause greater oxidative stress and ecotoxicological impacts than in marine systems where ·OH scavenging is a dominant reaction.

Novel application of two- and four-lobed noise-canceling passive integrated transponder antennas for tracking fish in areas of high ambient electromagnetic interference.

Passive integrated transponder (PIT) technology is a leading tool for tracking fish in freshwater systems. PIT is highly applicable for assessing fish passage at anthropogenic infrastructure (e.g., dams and floodgates); however, there are often complications in operating PIT antennas near these structures due to the ambient electromagnetic interference of metal and power-supply equipment. We designed a PIT antenna that is resistant to the effects of ambient electromagnetic interference (AEMI). This design uses lobes with balanced polarity within the antenna to neutralize AEMI within the vicinity of the antenna. This novel PIT antenna provides a more effective and cost-efficient option for researchers tracking fish in environments with high AEMI.

Coronary circulation enhances the aerobic performance of wild Pacific salmon.

Female Pacific salmon often experience higher mortality than males during their once-in-a-lifetime up-river spawning migration, particularly when exposed to secondary stressors (e.g. high temperatures). However, the underlying mechanisms remain unknown. One hypothesis is that female Pacific salmon hearts are more oxygen-limited than males and are less able to supply oxygen to the body's tissues during this demanding migration. Notably, female hearts have higher coronary blood flow, which could indicate a greater reliance on this oxygen source. Oxygen limitations can develop from naturally occurring coronary blockages (i.e., coronary arteriosclerosis) found in mature salmon hearts. If female hearts rely more heavily on coronary blood flow but experience similar arteriosclerosis levels as males, they will have disproportionately impaired aerobic performance. To test this hypothesis, we measured resting (RMR) and maximum metabolic rate (MMR), aerobic scope (AS) and acute upper thermal tolerance in coho salmon (Oncorhynchus kisutch) with an intact or artificially blocked coronary oxygen supply. We also assessed venous blood oxygen and chemistry (cortisol, ions, and metabolite concentrations) at different time intervals during recovery from exhaustive exercise. We found that coronary blockage impaired MMR, AS, and the partial pressure of oxygen in venous blood (PvO2) during exercise recovery but did not differ between sexes. Coronary ligation lowered acute upper thermal tolerance by 1.1°C. Though we did not find evidence of enhanced female reliance on coronary supply, our findings highlight the importance of coronary blood supply for mature wild salmon, where migration success may be linked to cardiac performance, particularly during warm water conditions.

Navigating Care Refusal and Noncompliance in Patients with Opioid Use Disorder.

BACKGROUND: For many emergency physicians (EPs), deciding whether or not to allow a patient suffering the ill effects of opioid use to refuse care is the most frequent and fraught situation in which they encounter issues of decision-making capacity, informed refusal, and autonomy. Despite the frequency of this issue and the well-known impacts of opioid use disorder on decision-making, the medical ethics community has offered little targeted analysis or guidance regarding these situations. DISCUSSION: As a result, EPs demonstrate significant variability in how they evaluate and respond to them, with highly divergent understandings and application of concepts such as decision-making capacity, informed consent, autonomy, legal repercussions, and strategies to resolve the clinical dilemma. In this paper, we seek to provide more clarity to this issue for the EPs. CONCLUSIONS: Successfully navigating this issue requires that EPs understand the specific effects that opioid use disorder has on decision-making, and how that in turn bears on the ethical concepts of autonomy, capacity, and informed refusal. Understanding these concepts can lead to helpful strategies to resolve these commonly-encountered dilemmas.

A genome-scale screen identifies sulfated glycosaminoglycans as pivotal in epithelial cell damage by Candida albicans.

Candidalysin is a cytolytic peptide produced by the opportunistic fungal pathogen Candida albicans. This peptide is a key virulence factor in mouse models of mucosal and hematogenously disseminated candidiasis. Despite intense interest in the role of candidalysin in C. albicans pathogenicity, its host cell targets have remained elusive. To fill this knowledge gap, we performed a genome-wide loss-of-function CRISPR screen in a human oral epithelial cell line to identify specific host factors required for susceptibility to candidalysin-induced cellular damage. Among the top hits were XYLT2, B3GALT6 and B3GAT3, genes that function in glycosaminoglycan (GAG) biosynthesis. Deletion of these genes led to the absence of GAGs such as heparan sulfate on the epithelial cell surface and increased resistance to damage induced by both candidalysin and live C. albicans. Biophysical analyses including surface plasmon resonance and atomic force and electron microscopy indicated that candidalysin physically binds to sulfated GAGs, facilitating its oligomerization or enrichment on the host cell surface. The addition of exogenous sulfated GAGs or the GAG analogue dextran sulfate protected cells against candidalysin-induced damage. Dextran sulfate, but not non-sulfated dextran, also inhibited epithelial cell endocytosis of C. albicans and fungal-induced epithelial cell cytokine and chemokine production. In a murine model of vulvovaginal candidiasis, topical dextran sulfate administration reduced host tissue damage and decreased intravaginal IL-1ß and neutrophil levels. Collectively, these data indicate that GAGs are epithelial cell targets of candidalysin and can be used therapeutically to protect cells from candidalysin-induced damage.

Naloxone prescription fills and use by patients treated for opioid use disorder by telehealth.

Background: It is unknown how many people in treatment for opioid use disorder (OUD) have naloxone, use naloxone, and what their perceptions and barriers to obtaining it are. Methods: This was a survey of patients treated in a large telehealth OUD program. Between December 6, 2023 and January 6, 2024, all patients who had access to the program's phone app (n=17,899 individuals, of whom 12,887 were in active treatment), were invited to complete an anonymous online survey. Results: There were 701 individuals who completed the survey. Nearly all patients (n=693, 99%) knew what naloxone is, and the majority (n=601, 86%) knew how to administer it. A quarter of these patients (n=177, 25%) reported either having naloxone used on themselves or using it on someone else. 161 patients (23%) reported taking a naloxone training course. Of patients who recalled receiving a prescription, 72% (n=382) filled the prescription, and 85% (n=321) reported that insurance paid for all or part of it. If filled, the naloxone was reported as used by 30 (8%) patients. If not filled, reasons were: already had it (n=55, 37%), did not think it was needed (n=54, 37%) or too expensive (n=36, 23%). Patients who reported knowing how to administer naloxone (OR 2.63 (95% CI 1.35-5.00) were more likely to fill the prescription. Conclusions: Patients prescribed naloxone in a telehealth treatment program filled the prescription 72% of the time, and when it was filled, 8% used the naloxone. Education and cost policy changes may reduce barriers to obtaining naloxone.