Treatment with dextroamphetamine decreases the reacquisition of cocaine self-administration: Consistency across social contexts.

RATIONALE: A return to cocaine use following abstinence frequently occurs in a social context, and the presence of other individuals using cocaine may contribute to the likelihood of use. Previous studies have reported that chronic d-amphetamine treatment decreases cocaine self-administration in laboratory animals and reduces a return to cocaine use following abstinence in humans. OBJECTIVE: The purpose of this study was to examine the effects of chronic d-amphetamine treatment on the reacquisition of cocaine use in rats self-administering cocaine in different social contexts. METHODS: Male and female rats were implanted with intravenous catheters and trained to self-administer cocaine during daily 6-hr sessions. After 14 days, cocaine self-administration was extinguished by substituting saline for the cocaine stimulus. At this time, rats were randomized to receive chronic treatment with either d-amphetamine or saline. After 9 days of extinction, cocaine was again made available during daily 6-hr sessions. At this time, rats were further randomized into three social conditions: (1) rats continued self-administering cocaine in isolation, (2) rats self-administered cocaine in the presence of a same-sex partner that also self-administered cocaine, or (3) rats self-administered cocaine in the presence of a same-sex partner that did not have access to cocaine. Daily treatment with d-amphetamine or saline continued for the duration of reacquisition testing. RESULTS: Chronic treatment with d-amphetamine decreased cocaine intake during reacquisition, but these effects were not influenced by the social context. No sex differences were observed. CONCLUSION: These data support previous studies reporting that d-amphetamine decreases cocaine intake and demonstrate its efficacy across social contexts.

Physical activity and temperature changes of Asian elephants (Elephas maximus) participating in eco-tourism activities and elephant polo.

Captive and domestic animals are often required to engage in physical activity initiated or organised by humans, which may impact their body temperature, with consequences for their health and welfare. This is a particular concern for animals such as elephants that face thermoregulatory challenges because of their body size and physiology. Using infrared thermography, we measured changes in skin temperature associated with two types of physical activity in ten female Asian elephants (Elephas maximus) at an eco-tourism lodge in Nepal. Six elephants took part in an activity relatively unfamiliar to the elephants-a polo tournament-and four participated in more familiar ecotourism activities. We recorded skin temperatures for four body regions affected by the activities, as well as an average skin temperature. Temperature change was used as the response variable in the analysis and calculated as the difference in elephant temperature before and after activity. We found no significant differences in temperature change between the elephants in the polo-playing group and those from the non-polo playing group. However, for both groups, when comparing the average skin body temperature and several different body regions, we found significant differences in skin temperature change before and after activity. The ear pinna was the most impacted region and was significantly different to all other body regions. This result highlights the importance of this region in thermoregulation for elephants during physical activity. However, as we found no differences between the average body temperatures of the polo and non-polo playing groups, we suggest that thermoregulatory mechanisms can counteract the effects of both physical activities the elephants engaged in.

Building the Infrastructure to Integrate Social Care in a Safety Net Health System.

A recent National Academies report recommended that health systems invest in new infrastructure to integrate social and medical care. Although many health systems routinely screen patients for social concerns, few health systems achieve the recommended model of integration. In this critical case study in an urban safety net health system, we describe the human capital, operational redesign, and financial investment needed to implement the National Academy recommendations. Using data from this case study, we estimate that other health systems seeking to build and maintain this infrastructure would need to invest $1 million to $3 million per year. While health systems with robust existing resources may be able to bootstrap short-term funding to initiate this work, we conclude that long-term investments by insurers and other payers will be necessary for most health systems to achieve the recommended integration of medical and social care. Researchers seeking to test whether integrating social and medical care leads to better patient and population outcomes require access to health systems and communities who have already invested in this model infrastructure. (Am J Public Health. 2024;114(6):619-625. https://doi.org/10.2105/AJPH.2024.307602).

Temporal and spatial drivers of the structure of macroinvertebrate assemblages associated with Laminaria hyperborea detritus in the northeast Atlantic.

Kelp forests occur on more than a quarter of the world's coastlines, serving as foundation species supporting high levels of biodiversity. They are also a major source of organic matter in coastal ecosystems, with the majority of primary production released and exported as detritus. Kelp detritus also provides food and shelter for macroinvertebrates, which comprise important components of inshore food-webs. Hitherto, research on kelp detritus-associated macroinvertebrate assemblages remains relatively limited. We quantified spatiotemporal variability in the structure of detritus-associated macroinvertebrate assemblages within Laminaria hyperborea forests and evaluated the influence of putative drivers of the observed variability in assemblages across eight study sites within four regions of the United Kingdom in May and September 2015. We documented 5167 individuals from 106 taxa with Malacostraca, Gastropoda, Isopoda and Bivalvia the most abundant groups sampled. Assemblage structure varied across months, sites, and regions, with highest richness in September compared to May. Many taxa were unique to individual regions, with few documented in all regions. Finally, key drivers of assemblage structure included detritus tissue nitrogen content, depth, sea surface temperature, light intensity, as well as L. hyperborea canopy density and canopy biomass. Despite their dynamic composition and transient existence, accumulations of L. hyperborea detritus represent valuable repositories of biodiversity and represent an additional kelp forest component which influences secondary productivity, and potentially kelp forest food-web dynamics.

Photoelectrochemical Proton-Coupled Electron Transfer of TiO2 Thin Films on Silicon.

TiO2 thin films are often used as protective layers on semiconductors for applications in photovoltaics, molecule-semiconductor hybrid photoelectrodes, and more. Experiments reported here show that TiO2 thin films on silicon are electrochemically and photoelectrochemically reduced in buffered acetonitrile at potentials relevant to photoelectrocatalysis of CO2 reduction, N2 reduction, and H2 evolution. On both n-type Si and irradiated p-type Si, TiO2 reduction is proton-coupled with a 1e-:1H+ stoichiometry, as demonstrated by the Nernstian dependence of the Ti4+/3+ E1/2 on the buffer pKa. Experiments were conducted with and without illumination, and a photovoltage of ∼0.6 V was observed across 20 orders of magnitude in proton activity. The 4 nm films are almost stoichiometrically reduced under mild conditions. The reduced films catalytically transfer protons and electrons to hydrogen atom acceptors, based on cyclic voltammogram, bulk electrolysis, and other mechanistic evidence. TiO2/Si thus has the potential to photoelectrochemically generate high-energy H atom carriers. Characterization of the TiO2 films after reduction reveals restructuring with the formation of islands, rendering TiO2 films as a potentially poor choice as protecting films or catalyst supports under reducing and protic conditions. Overall, this work demonstrates that atomic layer deposition TiO2 films on silicon photoelectrodes undergo both chemical and morphological changes upon application of potentials only modestly negative of RHE in these media. While the results should serve as a cautionary tale for researchers aiming to immobilize molecular monolayers on "protective" metal oxides, the robust proton-coupled electron transfer reactivity of the films introduces opportunities for the photoelectrochemical generation of reactive charge-carrying mediators.

Electronic isomerism in a heterometallic nickel-iron-sulfur cluster models substrate binding and cyanide inhibition of carbon monoxide dehydrogenase.

The nickel-iron carbon monoxide dehydrogenase (CODH) enzyme uses a heterometallic nickel-iron-sulfur ([NiFe4S4]) cluster to catalyze the reversible interconversion of carbon dioxide (CO2) and carbon monoxide (CO). These reactions are essential for maintaining the global carbon cycle and offer a route towards sustainable greenhouse gas conversion but have not been successfully replicated in synthetic models, in part due to a poor understanding of the natural system. Though the general protein architecture of CODH is known, the electronic structure of the active site is not well-understood, and the mechanism of catalysis remains unresolved. To better understand the CODH enzyme, we have developed a protein-based model containing a heterometallic [NiFe3S4] cluster in the Pyrococcus furiosus (Pf) ferredoxin (Fd). This model binds small molecules such as carbon monoxide and cyanide, analogous to CODH. Multiple redox- and ligand-bound states of [NiFe3S4] Fd (NiFd) have been investigated using a suite of spectroscopic techniques, including resonance Raman, Ni and Fe K-edge X-ray absorption spectroscopy, and electron paramagnetic resonance, to resolve charge and spin delocalization across the cluster, site-specific electron density, and ligand activation. The facile movement of charge through the cluster highlights the fluidity of electron density within iron-sulfur clusters and suggests an electronic basis by which CN- inhibits the native system while the CO-bound state continues to elude isolation in CODH. The detailed characterization of isolable states that are accessible in our CODH model system provides valuable insight into unresolved enzymatic intermediates and offers design principles towards developing functional mimics of CODH.

The Impact of Valsalva Manoeuvres and Exercise on Intracranial Pressure and Cerebrovascular Dynamics in Idiopathic Intracranial Hypertension.

Idiopathic intracranial hypertension (IIH) is a disease characterised by elevated intracranial pressure (ICP). The impact of straining and exercise on ICP regulation is poorly understood yet clinically relevant to IIH patient care. We sought to investigate the impact of Valsalva manoeuvres (VMs) and exercise on ICP and cerebrovascular haemodynamics in IIH. People with IIH were prospectively enrolled and had an intraparenchymal telemetric ICP sensor inserted. Three participants (age [mean ± standard deviation]: 40.3 ± 13.9 years) underwent continuous real-time ICP monitoring coupled with cerebrovascular haemodynamic assessments during VMs and moderate exercise. Participants had IIH with supine ICP measuring 15.3 ± 8.7 mmHg (20.8 ± 11.8 cm cerebrospinal fluid (CSF)) and sitting ICP measuring -4.2 ± 7.9 mmHg (-5.7 ± 10.7 cmCSF). During phase I of a VM ICP increased by 29.4 ± 13.5 mmHg (40.0 ± 18.4 cmCSF) but returned to baseline within 16 seconds from VM onset. The pattern of ICP changes during the VM phases was associated to that of changes in blood pressure, the middle cerebral artery blood velocity and prefrontal cortex haemodynamics. Exercise led to minimal effects on ICP. In conclusion, VM-induced changes in ICP were coupled to cerebrovascular haemodynamics and showed no sustained impact on ICP. Exercise did not lead to prolonged elevation of ICP. Those with IIH experiencing VMs (for example, during exercise and labour) may be reassured at the brief nature of the changes. Future research must look to corroborate the findings in a larger IIH cohort.

Limited Sustained Remission After Nucleos(t)ide Analog Withdrawal: Results From a Large, Global, Multiethnic Cohort of Patients With Chronic Hepatitis B (RETRACT-B Study).

INTRODUCTION: Complete viral suppression with nucleos(t)ide analogs (NAs) has led to a profound reduction in hepatocellular carcinoma and mortality among patients with chronic hepatitis B. Finite therapy yields higher rates of functional cure; however, initial hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) elevations are almost certain after treatment interruption. We aimed to analyze off-treatment outcomes beyond 12 months after NA cessation. METHODS: Patients with well-suppressed chronic hepatitis B who were hepatitis B e antigen-negative at NA cessation and remained off treatment without hepatitis B surface antigen (HBsAg) loss at 12 months were included (n = 945). HBV DNA and ALT fluctuations were allowed within the first 12 months. We used Kaplan-Meier methods to analyze outcomes beyond 12 months. Sustained remission was defined as HBV DNA <2,000 IU/mL and ALT <2× upper limit of normal (ULN) and an ALT flare as ALT ≥5× ULN. RESULTS: Cumulative probability of sustained remission was 29.7%, virological relapse was 65.2% with a mean peak HBV DNA of 5.0 ± 1.5 log 10 IU/mL, an ALT flare was 15.6% with a median peak ALT × ULN of 8.3 (5.7-11.3), HBsAg loss was 9.9% and retreatment was 34.9% at 48 months after NA cessation. A single occurrence of virological relapse or an ALT flare within the first 12 months off-treatment were associated with significantly lower rates of sustained remission beyond 12 months. DISCUSSION: Despite allowing for HBV DNA and ALT fluctuations within the first 12 months off-treatment, most patients without HBsAg loss did not maintain a sustained response thereafter. The best candidates for NA withdrawal are patients with low HBsAg levels at NA cessation, and those without profound or recurrent virological and biochemical relapses in the first off-treatment year.

Eating disorder symptoms and comorbid mental health risk among teens recruited to a digital intervention research study via two online approaches.

INTRODUCTION: It is crucial to identify and evaluate feasible, proactive ways to reach teens with eating disorders (EDs) who may not otherwise have access to screening or treatment. This study aimed to explore the feasibility of recruiting teens with EDs to a digital intervention study via social media and a publicly available online ED screen, and to compare the characteristics of teens recruited by each approach in an exploratory fashion. METHOD: Teens aged 14-17 years old who screened positive for a clinical/subclinical ED or at risk for an ED and who were not currently in ED treatment completed a baseline survey to assess current ED symptoms, mental health comorbidities, and barriers to treatment. Bivariate analyses were conducted to examine differences between participants recruited via social media and those recruited after completion of a widely available online EDs screen (i.e., National Eating Disorders Association [NEDA] screen). RESULTS: Recruitment of teens with EDs using the two online approaches was found to be feasible, with 934 screens completed and a total of 134 teens enrolled over 6 months: 77% (n = 103) via social media 23% (n = 31) via the NEDA screen. Mean age of participants (N = 134) was 16 years old, with 49% (n = 66) identifying as non-White, and 70% (n = 94) identifying as a gender and/or sexual minority. Teens from NEDA reported higher ED psychopathology scores (medium effect size) and more frequent self-induced vomiting and driven exercise (small effect sizes). Teens from NEDA also endorsed more barriers to treatment, including not feeling ready for treatment and not knowing where to find a counselor or other resources (small effect sizes). DISCUSSION: Online recruitment approaches in this study reached a large number of teens with an interest in a digital intervention to support ED recovery, demonstrating the feasibility of these outreach methods. Both approaches reached teens with similar demographic characteristics; however, teens recruited from NEDA reported higher ED symptom severity and barriers to treatment. Findings suggest that proactive assessment and intervention methods should be developed and tailored to meet the needs of each of these groups. PUBLIC SIGNIFICANCE: This study examined the feasibility of recruiting teens with EDs to a digital intervention research study via social media and NEDA's online screen, and demonstrated differences in ED symptoms among participants by recruitment approach.

Video accounts of first year pharmacy students' identification with the oath of a pharmacist.

INTRODUCTION: The Oath of a Pharmacist (OAP) includes principles that help to direct the practice of pharmacy. The primary objective of this study was to evaluate which OAP components appealed the most to pharmacy students through self-generated video recordings. The secondary objective was to explore students' perceptions of this activity by retrieving their feedback about future video development considerations. METHODS: First-year pharmacy students were invited by email to individually create a 1-min video that discussed an OAP tenet that resonated the most with them and why. The students were also asked: 1) If enhanced, would you use your video for self-promotion purposes? 2) Do you think this activity should be required or optional for future students? 3) What overall comments do you have about this activity? The study authors solely reviewed all submissions. RESULTS: Twenty-nine students developed videos and submitted responses to the associated queries. All students stated they would utilize their videos for self-promotion purposes, if enhanced. Although most students supported the future use of this activity, they were roughly split about whether it should be required or optional. A Communications course was one of the curriculum locales suggested to house this activity. CONCLUSIONS: Pharmacy students video-recorded themselves articulating which OAP segment meant the most to them and why. Most students recommended embedding future iterations into the curriculum. This activity leveraged OAP aspects to learn more about students' personal and professional motivations.

Photoelectrochemical CO2 Reduction to CO Enabled by a Molecular Catalyst Attached to High-Surface-Area Porous Silicon.

A high-surface-area p-type porous Si photocathode containing a covalently immobilized molecular Re catalyst is highly selective for the photoelectrochemical conversion of CO2 to CO. It gives Faradaic efficiencies of up to 90% for CO at potentials of -1.7 V (versus ferrocenium/ferrocene) under 1 sun illumination in an acetonitrile solution containing phenol. The photovoltage is approximately 300 mV based on comparisons with similar n-type porous Si cathodes in the dark. Using an estimate of the equilibrium potential for CO2 reduction to CO under optimized reaction conditions, photoelectrolysis was performed at a small overpotential, and the onset of electrocatalysis in cyclic voltammograms occurred at a modest underpotential. The porous Si photoelectrode is more stable and selective for CO production than the photoelectrode generated by attaching the same Re catalyst to a planar Si wafer. Further, facile characterization of the porous Si-based photoelectrodes using transmission mode FTIR spectroscopy leads to highly reproducible catalytic performance.

Immunophenotyping, Part I: Instrument Calibration and Reagent Qualification for Immunophenotyping Analysis of Human Peripheral Blood Mononuclear Cell Cultures.

Nanoparticles are increasingly used in biomedical applications to influence the way the immune system reacts to tumors and infectious disease-causing agents. Nanoparticles not-intended for immunomodulation can also influence immune responses by affecting immune cell subsets' viability and/or activity. While immunophenotyping is commonly used to assess the effects of drugs and nanoparticles on immune cell subsets, no standardized approach exists due to the breadth of available cell models and instrumentation. In this chapter, we describe a protocol for flow cytometer calibration and reagent qualification prior to its use in the immunophenotyping experiment. The strategies described herein can be adapted to other instruments. The subsequent chapter-immunophenotyping part II (Chap. 25 )-provides detailed instructions for applying this methodology to analyze nanoparticle effects on subsets of immune cells present in peripheral blood.

Immunophenotyping, Part II: Analysis of Nanoparticle Effects on the Composition and Activation Status of Human Peripheral Blood Mononuclear Cells.

The use of nanoparticles as drug delivery carriers requires analysis of their safety, which among other tests, includes immunotoxicity. Nanoparticles are also increasingly used for applications intended to specifically activate, inhibit, or modify the immune system's responses to improve the treatment of inflammatory and autoimmune disorders, cancer immunotherapy, and vaccines targeting cancer cells and viral and bacterial pathogens. In addition to the safety, the analysis of nanoparticles intended for immune system targeting includes mechanistic immunology investigations. Immunophenotyping provides researchers with a tool to assess the immune cell viability and activation status. These results provide mechanistic insights into nanoparticle efficacy and toxicity and therefore are of interest to the biomedical nanotechnology field. However, no standardized approaches exist due to the breadth of methods and instruments available for this analysis. This chapter provides detailed instructions for applying this methodology to analyze nanoparticle effects on subsets of immune cells present in peripheral blood. While this experimental strategy is specific to the NovoCyte 3005 flow cytometer, it can be adapted to other instruments. Instructions for instrument setup, calibration, and antibody qualification are described in this book's Chapter 24 , Immunophenotyping, part I.

Pediatrician perspectives on barriers and facilitators to discharge instruction comprehension and adherence for parents of children with medical complexity.

BACKGROUND: High rates of posthospitalization errors are observed in children with medical complexity (CMC). Poor parent comprehension of and adherence to complex discharge instructions can contribute to errors. Pediatrician views on common barriers and facilitators to parent comprehension and adherence are understudied. OBJECTIVE: To examine pediatrician perspectives on barriers and facilitators experienced by parents in comprehension of and adherence to inpatient discharge instructions for CMC. DESIGN, SETTINGS, AND PARTICIPANTS: We conducted a qualitative, descriptive study of attending pediatricians (n = 20) caring for CMC in inpatient settings (United States and Canada) and belonging to listservs for pediatric hospitalists/complex care providers. We used purposive/maximum variation sampling to ensure heterogeneity (e.g., hospital, region). MAIN OUTCOME AND MEASURES: A multidisciplinary team designed and piloted a semistructured interview guide with pediatricians who care for CMC. Team members conducted semistructured interviews via phone or video call. Interviews were audiorecorded and transcribed. We analyzed transcripts using content analysis; codes were derived a priori from a conceptual framework (based on the Pediatric Self-Management Model) and a preliminary transcript analysis. We applied codes and identified emerging themes. RESULTS: Pediatricians identified three themes as barriers and facilitators to discharge instruction comprehension and adherence: (1) regimen complexity, (2) access to the healthcare team (e.g., inpatient team, outpatient pediatrician, home nursing) and resources (e.g., medications, medical equipment), and (3) need for a family centered and health literacy-informed approach to discharge planning and education. Next steps include the assessment of parent perspectives on barriers and facilitators to discharge instruction comprehension and adherence for prents of CMC and the development of intervention strategies.

The rise of data-driven microscopy powered by machine learning.

Optical microscopy is an indispensable tool in life sciences research, but conventional techniques require compromises between imaging parameters like speed, resolution, field of view and phototoxicity. To overcome these limitations, data-driven microscopes incorporate feedback loops between data acquisition and analysis. This review overviews how machine learning enables automated image analysis to optimise microscopy in real time. We first introduce key data-driven microscopy concepts and machine learning methods relevant to microscopy image analysis. Subsequently, we highlight pioneering works and recent advances in integrating machine learning into microscopy acquisition workflows, including optimising illumination, switching modalities and acquisition rates, and triggering targeted experiments. We then discuss the remaining challenges and future outlook. Overall, intelligent microscopes that can sense, analyse and adapt promise to transform optical imaging by opening new experimental possibilities.

Factors Contributing to Disproportionate Burnout in Women Breast Imaging Radiologists: A Review.

Physician burnout continues to increase in prevalence and disproportionately affects women physicians. Breast imaging is a woman-dominated subspeciality, and therefore, worsening burnout among women physicians may have significant repercussions on the future of the breast imaging profession. Systemic and organizational factors have been shown to be the greatest contributors to burnout beyond individual factors. Based on the Mayo Model, we review the evidence regarding the 7 major organizational contributors to physician burnout and their potential disproportionate impacts on women breast radiologists. The major organizational factors discussed are work-life integration, control and flexibility, workload and job demands, efficiency and resources, finding meaning in work, social support and community at work, and organizational culture and values. We also propose potential strategies for institutions and practices to mitigate burnout in women breast imaging radiologists. Many of these strategies could also benefit men breast imaging radiologists, who are at risk for burnout as well.

Regression-based Deep-Learning predicts molecular biomarkers from pathology slides.

Deep Learning (DL) can predict biomarkers from cancer histopathology. Several clinically approved applications use this technology. Most approaches, however, predict categorical labels, whereas biomarkers are often continuous measurements. We hypothesize that regression-based DL outperforms classification-based DL. Therefore, we develop and evaluate a self-supervised attention-based weakly supervised regression method that predicts continuous biomarkers directly from 11,671 images of patients across nine cancer types. We test our method for multiple clinically and biologically relevant biomarkers: homologous recombination deficiency score, a clinically used pan-cancer biomarker, as well as markers of key biological processes in the tumor microenvironment. Using regression significantly enhances the accuracy of biomarker prediction, while also improving the predictions' correspondence to regions of known clinical relevance over classification. In a large cohort of colorectal cancer patients, regression-based prediction scores provide a higher prognostic value than classification-based scores. Our open-source regression approach offers a promising alternative for continuous biomarker analysis in computational pathology.

A 12-year experience in the management of blunt thoracic aortic injury in Otautahi Christchurch.

BACKGROUND: Blunt thoracic aortic injury (BTAI) is associated with a high mortality and is the second most common cause of death from trauma. The approach to major trauma, imaging technology and advancement in endovascular therapy have revolutionised the management of BTAI. Endovascular therapy has now become the gold standard technique replacing surgery with its high mortality and morbidity in unstable patients. We aim to assess the outcomes following management of BTAI. METHOD: This is a retrospective study of all patients with BTAI between 1 January 2010 and 1 January 2022. Data were obtained from electronic health records. The grading of BTAI severity was done based on the Society of Vascular Surgery (SVS) Criteria. RESULTS: Fifty patients were included in the study analysis. The most common cause of BTAI was due to high-speed motor vehicle accidents (MVA) (36 patients, 72%). Grade 1 and grade 3 BTAI injuries were mostly encountered in 40% and 30% of the study cohort, respectively. Twenty-three patients (46%) underwent thoracic endovascular aortic repair (TEVAR). There was no secondary aortic re-intervention, conversion to open surgery or aortic-related deaths at 30 days or at most recent follow-up. CONCLUSION: Management of BTAI in our centre compares well with currently published studies. Long-term studies are warranted to guide clinicians in areas of controversy in BTAI management.