Comparison of Administration of 8-Milligram and 4-Milligram Intranasal Naloxone by Law Enforcement During Response to Suspected Opioid Overdose - New York, March 2022-August 2023.

In 2021, an 8-mg intranasal naloxone product was approved by the Food and Drug Administration; however, no studies have examined outcomes among persons who receive the 8-mg naloxone product and those who receive the usual 4-mg product. During March 2022-August 2023, New York State Department of Health (NYSDOH) supplied some New York State Police (NYSP) troops with 8-mg intranasal naloxone; other troops continued to receive 4-mg intranasal naloxone to treat suspected opioid overdose. NYSP submitted detailed reports to NYSDOH when naloxone was administered. No significant differences were observed in survival, mean number of naloxone doses administered, prevalence of most postnaloxone signs and symptoms, postnaloxone anger or combativeness, or hospital transport refusal among 4-mg and 8-mg intranasal naloxone recipients; however, persons who received the 8-mg intranasal naloxone product had 2.51 times the risk for opioid withdrawal signs and symptoms, including vomiting, than did those who received the 4-mg intranasal naloxone product (95% CI = 1.51-4.18). This initial study suggests no benefits to law enforcement administration of higher-dose naloxone were identified; more research is needed to guide public health agencies in considering whether 8-mg intranasal naloxone confers additional benefits for community organizations.

Functional interactions between neurofibromatosis tumor suppressors underlie Schwann cell tumor de-differentiation and treatment resistance.

Schwann cell tumors are the most common cancers of the peripheral nervous system and can arise in patients with neurofibromatosis type-1 (NF-1) or neurofibromatosis type-2 (NF-2). Functional interactions between NF1 and NF2 and broader mechanisms underlying malignant transformation of the Schwann lineage are unclear. Here we integrate bulk and single-cell genomics, biochemistry, and pharmacology across human samples, cell lines, and mouse allografts to identify cellular de-differentiation mechanisms driving malignant transformation and treatment resistance. We find DNA methylation groups of Schwann cell tumors can be distinguished by differentiation programs that correlate with response to the MEK inhibitor selumetinib. Functional genomic screening in NF1-mutant tumor cells reveals NF2 loss and PAK activation underlie selumetinib resistance, and we find that concurrent MEK and PAK inhibition is effective in vivo. These data support a de-differentiation paradigm underlying malignant transformation and treatment resistance of Schwann cell tumors and elucidate a functional link between NF1 and NF2.

Elephant TP53-RETROGENE 9 induces transcription-independent apoptosis at the mitochondria.

Approximately 20 TP53 retrogenes exist in the African and Asian elephant genomes (Loxodonta Africana, Elephas Maximus) in addition to a conserved TP53 gene that encodes a full-length protein. Elephant TP53-RETROGENE 9 (TP53-R9) encodes a p53 protein (p53-R9) that is truncated in the middle of the canonical DNA binding domain. This C-terminally truncated p53 retrogene protein lacks the nuclear localization signals and oligomerization domain of its full-length counterpart. When expressed in human osteosarcoma cells (U2OS), p53-R9 binds to Tid1, the chaperone protein responsible for mitochondrial translocation of human p53 in response to cellular stress. Tid1 expression is required for p53-R9-induced apoptosis. At the mitochondria, p53-R9 binds to the pro-apoptotic BCL-2 family member Bax, which leads to caspase activation, cytochrome c release, and cell death. Our data show, for the first time, that expression of this truncated elephant p53 retrogene protein induces apoptosis in human cancer cells. Understanding the molecular mechanism by which the additional elephant TP53 retrogenes function may provide evolutionary insight that can be utilized for the development of therapeutics to treat human cancers.

In vitro testing of a funnel-tip catheter with different clot types to decrease clot migration in mechanical thrombectomy.

BACKGROUND: Mechanical thrombectomy is the standard treatment for acute ischemic stroke in patients with large vessel occlusion and can be performed up to 24h after symptom onset. Despite high recanalization rates, embolism in new territories has been reported in 8.6% of the cases. Causes for this could be clot abruption during stent retrieval into the smaller opening of a standard distal access catheter, and antegrade blood flow via collaterals despite proximal balloon protection. A funnel-shaped tip with a larger internal diameter was developed to increase the rate of first-pass recanalization and to improve the safety and efficacy of mechanical thrombectomy. METHODS: This in vitro study compared the efficacy of a funnel-shaped tip with a standard tip in combination with different clot compositions. Mechanical thrombectomy was performed 80 times for each tip, using two stent retrievers (Trevo XP ProVue 3/20 mm, 4/20 mm) and four different clot types (hard vs. soft clots, 0-24h vs. 72h aged clots). RESULTS: Significantly higher first-pass recanalization rates (mTICI 3) were observed for the funnel-shaped tip, 70.0% versus 30.0% for the standard tip (absolute difference, 32; relative difference 57.1%; P < .001), regardless of the clot type and stent retriever. Recanalization could be increased using harder Chandler loop clots versus softer statically generated clots, as well as 0-24h versus 72h aged clots, respectively. CONCLUSION: The funnel-shaped tip achieved higher first-pass recanalization rates than the smaller standard tip and lower rates of clot abruption at the tip. Clot compositions and aging times impacted recanalization rates.

Farm animal careers and perception of 'fit' in undergraduate veterinary students: A mixed methods study.

BACKGROUND: Recruitment and retention of farm veterinarians have been the focus of recent research. Previous work suggests that a feeling of 'fit' is important for students to consider a farm career. The aim of this study was to identify whether students feel that they 'fit' in farm practice and reasons for their answer. METHODS: An online survey was distributed to students at all British and Irish veterinary schools. A mixed methods approach was considered, with thematic analysis on free text answers and regression analysis on demographic variables. RESULTS: Thematic analysis identified six themes: career opportunities, nature of farm veterinary work, relationships and interactions, individual experiences, expectations and perceptions, and no perceived barriers. Females, marginalised ethnic groups and those from an urban/suburban background were all identified as having significantly (p < 0.05) less agreement with the statement 'I feel able to pursue a career in farm practice'. LIMITATIONS: Survey limitations include those with a clear bias being likely to respond. However, alignment of the qualitative and quantitative results increased confidence in the findings of this mixed methods approach. CONCLUSION: This study confirms that biases that exist within wider society do have an influence on veterinary undergraduates' intentions to pursue a farm animal career. This is vital to consider both at a university level and when considering students' experiences on placements. Urgent action is required to improve inclusivity in the farm animal veterinary sector.

Naloxone administration by law enforcement officers in New York State (2015-2020).

BACKGROUND: The COVID-19 pandemic has amplified the need for wide deployment of effective harm reduction strategies in preventing opioid overdose mortality. Placing naloxone in the hands of key responders, including law enforcement officers who are often first on the scene of a suspected overdose, is one such strategy. New York State (NYS) was one of the first states to implement a statewide law enforcement naloxone administration program. This article provides an overview of the law enforcement administration of naloxone in NYS between 2015 and 2020 and highlights key characteristics of over 9000 opioid overdose reversal events. METHODS: Data in naloxone usage report forms completed by police officers were compiled and analyzed. Data included 9133 naloxone administration reports by 5835 unique officers located in 60 counties across NYS. Descriptive statistics were used to examine attributes of the aided individuals, including differences between fatal and non-fatal incidents. Additional descriptive analyses were conducted for incidents in which law enforcement officers arrived first at the scene of suspected overdose. Comparisons were made to examine year-over-year trends in administration as naloxone formulations were changed. Quantitative analysis was supplemented by content analysis of officers' notes (n = 2192). RESULTS: In 85.9% of cases, law enforcement officers arrived at the scene of a suspected overdose prior to emergency medical services (EMS) personnel. These officers assessed the likelihood of an opioid overdose having occurred based on the aided person's breathing status and other information obtained on the scene. They administered an average of 2 doses of naloxone to aided individuals. In 36.8% of cases, they reported additional administration of naloxone by other responders including EMS, fire departments, and laypersons. Data indicated the aided survived the suspected overdose in 87.4% of cases. CONCLUSIONS: With appropriate training, law enforcement personnel were able to recognize opioid overdoses and prevent fatalities by administering naloxone and carrying out time-sensitive medical interventions. These officers provided life-saving services to aided individuals alongside other responders including EMS, fire departments, and bystanders. Further expansion of law enforcement naloxone administration nationally and internationally could help decrease opioid overdose mortality.

Impact of COVID-19 lockdown: Domestic and child abuse in Bridgend.

INTRODUCTION: Financial stress, social stress and lack of support at home can precipitate domestic and child abuse (World Health Organization, 2020). These factors have been exacerbated by the COVID-19 pandemic (NSPCC, 2020b) (NSPCC, 2020a). We hypothesise an increase in Bridgend's domestic and child abuse during lockdown. METHOD: Data was collected retrospectively from 23rd March to 30th September 2020 and compared to the same time period in 2019. Wales-wide data on domestic abuse was shared by the Welsh Government's Live Fear free helpline. Local data was shared by domestic abuse charity CALAN, the Emergency Department (ED) and Paediatric Department of Princess of Wales Hospital (POWH). RESULTS: During lockdown, Live Fear Free reported increasing average monthly contact across Wales in 2020 (511 April; 631 December). Locally, CALAN reported a 190% increase in self-referrals and a 198% increase in third party referrals, but there was a 36% decrease in referrals from Police for domestic abuse. The Paediatric Department observed a 67% decrease in child protection medical examinations (CPMEs) undertaken (52 vs. 17). 23 examinations in 2019 were referred from schools compared to 1 in 2020. There was a greater proportion of self-referrals for CPMEs in 2020. ED child protection referrals increased from 189 (2019) to 204 (2020). CONCLUSION: There was an increase in self-referrals to local support services for domestic and child abuse concerns and an increase in referrals from families/friends for child protection concerns. This was not the case with police, ED and schools/nurseries referrals. This suggests reduced engagement with public sector organisations during lockdown which services should consider.

Accuracy of heart girth tapes in the estimation of weights of pre-weaned calves.

BACKGROUND: Heart girth tapes (HGTs) are often used as an alternative to weight scales for calves. This study investigated the accuracy of HGT in estimating bodyweight and daily liveweight gain (DWLG) of pre-weaned calves, and the impact of inter-observer variation. METHOD: In Study 1, 119 calves were weighed using HGT and electronic scales on multiple occasions. Mixed-effects models for both bodyweight and DLWG were used to determine the accuracy of HGT compared to the electronic scales. Simulation data were used to further analyse the accuracy of DLWG estimation including for factors such as the effect of group size on group DLWG estimates.In Study 2, 10 observers weighed 20 pre-weaned calves, using HGT and electronic scales. Mixed-effect model was used to investigate the impact of different observers on the accuracy of HGT on measuring bodyweights. RESULTS: Mixed-effects model results suggest HGT provides a relatively accurate estimation of weight (MAE: 2.66 kg) and relatively inaccurate estimation of DLWG (MAE 0.10 kg/d). Simulated data identified associations between time between weight dates and error in DLWG estimation, with MAE of individual DLWG estimation decreasing from 0.43 kg/d when 14 days apart to 0.08 kg/d when 70 days apart. Increased calf numbers reduced error rates of group DLWG estimation, with <0.05 kg/d error achieved in >90% of simulations when 12 calves were weighed 70 days apart. CONCLUSIONS: HGTs are relatively accurate at estimating individual bodyweights but are unreliable methods for measuring DLWG in individual calves, particularly weighed within a short-time period. Estimates at group level however are relatively accurate, providing there is a suitable period of time between weigh dates and an appropriate number of calves per group.

[(VIVO)2MII5] (M = Ni, Co) Anderson wheels.

Heterometallic Anderson wheels of formula [(VIVO)2MII5(hmp)10Cl2](ClO4)2·2MeOH (M = Ni, 1; Co, 2) have been synthesised from the solvothermal reaction of M(ClO4)2·6H2O and VCl3 with hmpH (2-(hydroxymethyl)pyridine). The metallic skeleton describes a centred hexagon, with the two vanadyl ions sitting on opposing sides of the outer ring. Magnetic susceptibility and magnetisation measurements indicate the presence of both ferromagnetic and antiferromagnetic exchange interactions. Theoretical calculations based on density functional methods reproduce both the sign and strength of the exchange interactions found experimentally, and rationalise the parameters extracted.

Effects of Vancomycin on Persistent Pain-Stimulated and Pain-Depressed Behaviors in Female Fischer Rats With or Without Voluntary Access to Running Wheels.

The present experiments determined the effects of the narrow-spectrum antibiotic vancomycin on inflammatory pain-stimulated and pain-depressed behaviors in rats. Persistent inflammatory pain was modeled using dilute formalin (0.5%). Two weeks of oral vancomycin administered in drinking water attenuated Phase II formalin pain-stimulated behavior, and prevented formalin pain-depressed wheel running. Fecal microbiota transplantation produced a non-significant trend toward reversal of the vancomycin effect on pain-stimulated behavior. Vancomycin depleted Firmicutes and Bacteroidetes populations in the gut while having a partial sparing effect on Lactobacillus species and Clostridiales. The vancomycin treatment effect was associated with an altered profile in amino acid concentrations in the gut with increases in arginine, glycine, alanine, proline, valine, leucine, and decreases in tyrosine and methionine. These results indicate that vancomycin may have therapeutic effects against persistent inflammatory pain conditions that are distal to the gut. PERSPECTIVE: The narrow-spectrum antibiotic vancomycin reduces pain-related behaviors in the formalin model of inflammatory pain. These data suggest that manipulation of the gut microbiome may be one method to attenuate inflammatory pain amplitude.

Attitudes of UK veterinary students towards careers in the production animal sector: A mixed methods approach.

BACKGROUND: Within the production animal sector, it has long been forecast that demand for veterinary services could outstrip supply. This study aims to identify factors influencing veterinary undergraduates' attitudes towards a career in farm animal veterinary practice and how those factors may be influenced by their experiences during their time as an undergraduate. METHODS: An online survey was distributed to all vet schools in the UK and Ireland. Thematic analysis and descriptive data analysis were performed on the 1146 responses received. RESULTS: Seven themes were identified: relationships, preferences and interest, fit, direct experience, fear, ethics and values and lifestyle. When considering first job choice, extra mural studies (EMS) and personal interest (60% and 75% of respondents respectively) were very influential. Factors that appeal or put off respondents from a career in farm animal varied dependent on anticipated first job (p < 0.001), but working hours and out of hours were consistently identified as barriers. CONCLUSION: The results highlight the importance of EMS being more transparent about the profession and using the opportunity to discuss undergraduate concerns regarding farm animal practice.

The structural manipulation of a series of Ni4 defective dicubanes: Synthesis, X-ray Structures, Magnetic and Computational analyses.

We report the synthesis and characterization of four new tetranuclear Ni(ii) complexes, C1-C4, all of which exhibit defective dicubane cores. C1-C4 are derived from the same salicylaldoxime derived ligand, H2L1. Complexes C1 and C4 have isostructural cores, differing in structure only by solvate molecules. Magnetic and computational analyses have revealed that complexes C1, C2, and C4 exhibit competing ferro- and antiferromagnetic interactions, however the different solvated species in C1 and C4 leads to notably different magnitudes in their magnetic coupling constants. Theoretical magneto-structural studies show that the pairwise magnetic exchange interaction is highly dependent on the Ni-X-Ni angle, as revealed by orbital overlap calculations.

The impact of stormwater biofilter design and operational variables on nutrient removal - a statistical modelling approach.

Biofiltration systems can help mitigate the impact of urban runoff as they can treat, retain and attenuate stormwater. It is important to select the optimal design characteristics of biofilters (e.g., vegetation, filter media depth) to ensure high treatment performance. Operational conditions (e.g., infiltration rate) can also lead to significant changes in biofilter treatment performance over time. The impact of specific operational conditions on water quality treatment performance of stormwater biofilters is still not well understood. Furthermore, despite the importance of design characteristics and operational conditions on biofilter treatment performance, there is a lack of models that can be used to determine the optimal design and operation. In this paper, we developed a series of statistical models to predict the Total Phosphorus (TP) and Total Nitrogen (TN) removal performance of stormwater biofilters using various numbers of design characteristics and operational conditions. These statistical models were tested using data collected from four extensive laboratory-scale biofilter column studies. It was found that all models performed relatively well with a Nash-Sutcliffe Efficiency (NSE) of 0.42 - 0.61 for TP and 0.37 - 0.63 for TN. The most important design characteristics were filter media type and depth for TP treatment, and vegetation type and submerged zone depth for TN treatment. In addition, infiltration rate and inflow concentrations were the operational conditions that greatly influence outflow TP and TN concentrations from stormwater biofilters. As such, these variables need to be carefully considered when designing and operating stormwater biofilters. Sensitivity analysis results indicate that the model was quite sensitive to all regression coefficients and intercepts. Additional modelling exercises show that the model could be further simplified by reducing the number of cross-correlated parameters. These models can be used by practitioners for not just optimising the design, but also operating biofilters using real-time monitoring and control to achieve optimum performance.

Semiconductor Quantum Dots as Components of Photoactive Supramolecular Architectures.

Luminescent quantum dots (QDs) are colloidal semiconductor nanocrystals consisting of an inorganic core covered by a molecular layer of organic surfactants. Although QDs have been known for more than thirty years, they are still attracting the interest of researchers because of their unique size-tunable optical and electrical properties arising from quantum confinement. Moreover, the controlled decoration of the QD surface with suitable molecular species enables the rational design of inorganic-organic multicomponent architectures that can show a vast array of functionalities. This minireview highlights the recent progress in the use of surface-modified QDs - in particular, those based on cadmium chalcogenides - as supramolecular platforms for light-related applications such as optical sensing, triplet photosensitization, photocatalysis and phototherapy.

In vitro testing of a funnel-shaped tip catheter model to decrease clot migration during mechanical thrombectomy.

One limitation of mechanical thrombectomy (MT) is clot migration during procedure. This might be caused by abruption of the trapped thrombus at the distal access catheter (DAC) tip during stent-retriever retraction due to the cylindrical shaped tip of the DAC. Aiming to solve this problem, this study evaluates the proof-of-concept of a new designed funnel-shaped tip, in an experimental in vitro setting. Two catheter models, one with a funnel-shaped tip and one with a cylindrical-shaped tip, were compared in an experimental setup. For MT a self-made vessel model and thrombi generated from pig's blood were used. MT was performed 20 times for each device using two different stent-retrievers, 10 times respectively. For the funnel-shaped model: for both stent-retrievers (Trevo XP ProVue 3/20 mm; Trevo XP ProVue 4/20 mm) MT was successful at first pass in 9/10 (90%), respectively. For the cylindrical-shaped model: MT was successful at first pass in 5/10 (50%) with the smaller stent-retriever and in 6/10 (60%) with the larger stent-retriever. The experiments show a better recanalization rate for funnel-shaped tips, than for cylindrical-shaped tips. These results are indicating a good feasibility for this new approach, thus the development of a prototype catheter seems reasonable.

Biotreatment technologies for stormwater harvesting: critical perspectives.

Biotreatment technologies offer many advantages for passive stormwater treatment before harvesting, but performance can be variable and sensitive to system design, construction, operation and maintenance. While there is substantial research underpinning pollutant removal, hydraulic function, internal processes and optimal design, specific focus upon stormwater harvesting is relatively limited. Recent advances in system design include testing media amendments for targeted pollutant removal, enhanced pathogen removal using antimicrobial plants, and broadening technology application. However, the production of reliable fit-for-purpose water requires the development of robust validation methodologies to meet public safety expectations. While foundation studies exist, more needs to be done to extend the validation framework, monitor and control system performance and operation in real-time, and apply standards and regulatory checks.

Plant-Microbe Interactions Drive Denitrification Rates, Dissolved Nitrogen Removal, and the Abundance of Denitrification Genes in Stormwater Control Measures.

The microbial community and function along with nitrate/nitrite (NOx) removal rates, and nitrogen (N) partitioning into "uptake", "denitrification", and "remaining" via isotope tracers, were studied in soil bioretention mesocolumns (8 unique plant species). Total denitrification gene reads per million (rpm) were positively correlated with % denitrified ( r = 0.69) but negatively correlated with total NOx removal following simulated rain events ( r = -0.79). This is likely due to plant-microbe interactions. Plant species with greater root volume, plant and microbial assimilation %, and NOx removal % had lower denitrification genes and rates. This implies that although microorganisms have access to N, advantageous functions, like denitrification, may not increase. At the conclusion of the 1.5-year experiment, the microbial community was strongly influenced by plant species within the Top zone dominated by plant roots, and the presence or absence of a saturated zone influenced the microbial community within the Bottom zone. Leptospermum continentale was an outlier from the other plants and had much lower denitrification gene rpm (average 228) compared to the other species (range: 277 to 413). The antimicrobial properties and large root volume of Leptospermum continentale likely caused this denitrification gene depression.

Delta/mu opioid receptor interactions in operant conditioning assays of pain-depressed responding and drug-induced rate suppression: assessment of therapeutic index in male Sprague Dawley rats.

RATIONALE AND OBJECTIVES: Although delta/mu receptor interactions vary as a function of behavioral endpoint, there have been no assessments of these interactions using assays of pain-depressed responding. This is the first report of delta/mu interactions using an assay of pain-depressed behavior. METHODS: A mult-cycle FR10 operant schedule was utilized in the presence of (nociception) and in the absence of (rate suppression) a lactic acid inflammatory pain-like manipulation. SNC80 and methadone were used as selective/high efficacy delta and mu agonists, respectively. Both SNC80 and methadone alone produced a dose-dependent restoration of pain-depressed responding and dose-dependent response rate suppression. Three fixed ratio mixtures, based on the relative potencies of the drugs in the nociception assay, also produced dose-dependent antinociception and sedation. Isobolographic analysis indicated that all three mixtures produced supra-additive antinociceptive effects and simply additive sedation effects. CONCLUSIONS: The therapeutic index (TI) inversely varied as a function of amount of SNC80 in the mixture, such that lower amounts of SNC80 produced a higher TI, and larger amounts produced a lower TI. Compared to literature using standard pain-elicited assays, the orderly relationship between SNC80 and TI reported here may be a unique function of assessing pain-depressed behavior.