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Overdose fatalities are increasingly attributed to synthetic opioids, including fentanyl, which may be added to samples of illicit substances unknowingly to the user. As recently as April 2023, the Centers for Disease Control and Prevention has also raised awareness of the risks of xylazine, an animal tranquilizer that has been found in adulterated samples of illicit substance. A growing body of evidence supports the use of drug testing services, including fentanyl and xylazine test strips, to reduce the risks associated with substance use and prevent fatal overdoses. Emergency medical services clinicians serve on the frontline of the opioid epidemic and are uniquely positioned to distribute harm reduction materials. In this article, we advocate for emergency medical services to distribute fentanyl and xylazine test strips. We also critically evaluate legal and other barriers to implementation.

Background The veterinary sedative xylazine is increasingly found in illicit fentanyl and has been associated with numerous health harms. Xylazine test strips (XTS) are an emerging technology that can theoretically assist consumers in avoiding xylazine, but they require real-world validation. We leverage community-based drug checking program data to compare real-world XTS performance to ‘gold standard’ methods. Methods Samples were initially assessed by dissolving 1 mg of drug product in 1 mL water and dipping an XTS (“first generation” Wisebatch™) in the sample. Subsequently, confirmatory testing was performed by sending samples to the National Institute of Standards and Technology for qualitative analysis using direct analysis in real-time mass spectrometry (DART-MS). A subset was analyzed quantitatively with liquid chromatography gas spectrometry (LC–MS) to quantify xylazine, fentanyl, and other compounds. Results A total of n = 1570 drug samples were analyzed between June 2023 and May 2025, and a total of n = 801 XTS were used. N = 715 comparisons between xylazine test strips and mass spectrometry results could be made, including n = 333 among samples that tested positive for fentanyl. Of these, n = 63 samples were confirmed to contain xylazine by mass spectrometry, of which the majority contained low concentrations (average concentration 2.3%; 78% of samples contained less than < 1% xylazine by weight). Of the 63, n = 34 were correctly identified as positive by XTS, yielding sensitivity of 54.0 %. Of n =  270 xylazine negative samples, n = 235 were correctly categorized (specificity = 87.0%). Most false positives occurred with lidocaine present. Conclusions In our sample, with a large percentage of low concentration xylazine samples, “first generation” Wisebatch XTS had a relatively low sensitivity, but higher specificity. This highlights the value of confirmatory testing and the complicated and often confusing nature of point-of-care test strips for novel substance detection. Lot testing and validation studies are needed to improve quality control in this area.

Use of immunoassay test strips for the detection of fentanyl in drug samples has become increasingly commonplace in harm reduction, law enforcement, public health, customs, and forensic science settings. With the increase of xylazine in the drug supply in recent years, use of xylazine test strips has also begun to take root. As adoption and implementation of this tool continues, a desire to implement test strips for other drugs may emerge. However, since these strips are designed for urine testing, it is important to understand their applicability to testing drugs themselves. In this work, we investigate the utility of seven types of urine immunoassay test strips – amphetamine, benzodiazepine, cocaine, methamphetamine, nitazene, opiate, and xylazine – for drug checking applications. Reproducibility, sensitivity, cross-reactivity, and the effect of prolonged exposure to elevated temperatures were studied. Generally, the tests were found to be reproducible, able to detect trace (µg/mL) levels of the analyte of interest, and minimally affected by prolonged storage at elevated temperatures. Nearly all tests showed cross-reactivity with compounds other than the analyte of interest, highlighting the need to better understand these limitations prior to implementation in a drug checking scenario (that may involve additional chemical analysis on or off site). The viability of expired cocaine, fentanyl, and methamphetamine and test strips was also interrogated, and little to no change in sensitivity was found even though the tests were multiple years expired.

Social risks, or adverse social conditions associated with poor health, are prevalent in emergency department (ED) patients, but little is known about how the prevalence of social risk compares to a patient's reported social need, which incorporates patient preference for intervention. The goal of this study was to describe the relationship between social risk and social need, and identify factors associated with differential responses to social risk and social need questions. We conducted a cross-sectional study with 48 hours of time-shift sampling in a large urban ED. Consenting patients completed a demographic questionnaire and assessments of social risk and social need. We applied descriptive statistics to the prevalence of social risk and social need, and multivariable logistic regression to assess factors associated with social risk, social need, or both. Of the 269 participants, 100 (37%) reported social risk, 83 (31%) reported social need, and 169 (63%) reported neither social risk nor social need. Although social risk and social need were significantly associated (p < 0.01), they incompletely overlapped. Over 50% in each category screened positive in more than one domain (eg, housing instability, food insecurity). In multivariable models, those with higher education (adjusted odds ratio [aOR] 0.44 [95% confidence interval {CI}, 0.24-0.80]) and private insurance (aOR 0.50 [95% CI, 0.29-0.88]) were less likely to report social risk compared to those with lower education and state/public insurance, respectively. Spanish-speakers (aOR 4.07 [95% CI, 1.17-14.10]) and non-Hispanic Black patients (aOR 5.00 [95% CI, 1.91-13.12]) were more likely to report social need, while those with private insurance were less likely to report social need (private vs state/public: aOR 0.13 [95% CI, 0.07-0.26]). Approximately one-third of patients in a large, urban ED screened positive for at least one social risk or social need, with over half in each category reporting risk/need across multiple domains. Different demographic variables were associated with social risk vs social need, suggesting that individuals with social risks differ from those with social needs, and that screening programs should consider including both assessments.

Background Oritavancin, a long-acting lipoglycopeptide approved for use in acute bacterial skin and skin structure infections, has limited data evaluating use in serious infections due to Gram-positive organisms. We aimed to assess the effectiveness and safety of oritavancin for consolidative treatment of Gram-positive bloodstream infections (BSI), including infective endocarditis (IE). Methods We conducted a retrospective cohort study evaluating adult patients admitted to University of Colorado Hospital from March 2016 to January 2022 who received  ≥  1 oritavancin dose for treatment of Gram-positive BSI. Patients were excluded if the index culture was drawn at an outside facility or were > 89 years of age. The primary outcome was a 90-day composite failure (clinical or microbiological failure) in those with 90-day follow-up. Secondary outcomes included individual components of the primary outcome, acute kidney injury (AKI), infusion-related reactions (IRR), and institutional cost avoidance. Results Overall, 72 patients were included. Mean ± SD age was 54 ± 16 years, 61% were male, and 10% had IE. Organisms most commonly causing BSI were Staphylococcus aureus (68%, 17% methicillin-resistant), followed by Streptococcus spp. (26%), and Enterococcus spp. (10%). Patients received standard-of-care antibiotics before oritavancin for a median (IQR) of 11 (5–17) days. Composite failure in the clinically evaluable population (n = 64) at 90-days occurred in 14% and was composed of clinical and microbiological failure, which occurred in 14% and 5% of patients, respectively. Three patients (4%) experienced AKI after oritavancin, and two (3%) experienced an IRR. Oritavancin utilization resulted in earlier discharge for 94% of patients corresponding to an institutional cost-avoidance of $3,055,804 (mean $44,938/patient) from 1,102 hospital days saved (mean 16 days/patient). Conclusions The use of oritavancin may be an effective sequential therapy for Gram-positive BSI to facilitate early discharge resulting in institutional cost avoidance.

Microbial adhesion to medical devices is common for hospital-acquired infections, particularly for urinary catheters. If not properly treated these infections cause complications and exacerbate antimicrobial resistance. Catheter use elicits bladder inflammation, releasing host serum proteins, including fibrinogen (Fg), into the bladder, which deposit on the urinary catheter. Enterococcus faecalis uses Fg as a scaffold to bind and persist in the bladder despite antibiotic treatments. Inhibition of Fg–pathogen interaction significantly reduces infection. Here, we show deposited Fg is advantageous for uropathogens E. faecalis , Escherichia coli , Pseudomonas aeruginosa , K. pneumoniae , A. baumannii , and C. albicans , suggesting that targeting catheter protein deposition may reduce colonization creating an effective intervention for catheter-associated urinary tract infections (CAUTIs). In a mouse model of CAUTI, host-protein deposition was reduced, using liquid-infused silicone catheters, resulting in decreased colonization on catheters, in bladders, and dissemination in vivo. Furthermore, proteomics revealed a significant decrease in deposition of host-secreted proteins on liquid-infused catheter surfaces. Our findings suggest targeting microbial-binding scaffolds may be an effective antibiotic-sparing intervention for use against CAUTIs and other medical device infections.

Eukaryotic ribosome biogenesis is initiated with the transcription of pre-ribosomal RNA at the 5’ external transcribed spacer, which directs the early association of assembly factors but is absent from the mature ribosome. The subsequent co-transcriptional association of ribosome assembly factors with pre-ribosomal RNA results in the formation of the small subunit processome. Here we show that stable rRNA domains of the small ribosomal subunit can independently recruit their own biogenesis factors in vivo. The final assembly and compaction of the small subunit processome requires the presence of the 5’ external transcribed spacer RNA and all ribosomal RNA domains. Additionally, our cryo-electron microscopy structure of the earliest nucleolar pre-ribosomal assembly - the 5’ external transcribed spacer ribonucleoprotein – provides a mechanism for how conformational changes in multi-protein complexes can be employed to regulate the accessibility of binding sites and therefore define the chronology of maturation events during early stages of ribosome assembly.

Facilitating coexistence between people and wildlife is a major conservation challenge in East Africa. Some conservation models aim to balance the needs of people and wildlife, but the effectiveness of these models is rarely assessed. Using a case‐study approach, we assessed the ecological performance of a pastoral area in northern Tanzania (Manyara Ranch) and established a long‐term wildlife population monitoring program (carried out intermittently from 2003 to 2008 and regularly from 2011 to 2019) embedded in a distance sampling framework. By comparing density estimates of the road transect‐based long‐term monitoring to estimates derived from systematically distributed transects, we found that the bias associated with nonrandom placement of transects was nonsignificant. Overall, cattle and sheep and goat reached the greatest densities and several wildlife species occurred at densities similar (zebra, wildebeest, waterbuck, Kirk's dik‐dik) or possibly even greater (giraffe, eland, lesser kudu, Grant's gazelle, Thomson's gazelle) than in adjacent national parks in the same ecosystem. Generalized linear mixed models suggested that most wildlife species (8 out of 14) reached greatest densities during the dry season, that wildlife population densities either remained constant or increased over the 17‐year period, and that herbivorous livestock species remained constant, while domestic dog population decreased over time. Cross‐species correlations did not provide evidence for interference competition between grazing or mixed livestock species and wildlife species but indicate possible negative relationships between domestic dog and warthog populations. Overall, wildlife and livestock populations in Manyara Ranch appear to coexist over the 17‐year span. Most likely, this is facilitated by existing connectivity to adjacent protected areas, effective anti‐poaching efforts, spatio‐temporal grazing restrictions, favorable environmental conditions of the ranch, and spatial heterogeneity of surface water and habitats. This long‐term case study illustrates the potential of rangelands to simultaneously support wildlife conservation and human livelihood goals if livestock grazing is restricted in space, time, and numbers. To provide evidence for livestock–wildlife coexistence, we present data on long‐term (intermittently from 2003 to 2008 and regularly from 2011 to 2019) monitoring and population dynamics of livestock and wildlife species in a managed pastoral area in northern Tanzania. Our results show constant livestock population trajectories and constant to increasing wildlife population trends. This case study illustrates the potential of rangelands to simultaneously support wildlife conservation and human livelihood goals if livestock grazing is managed sustainably.

Characterizing dust attenuation is crucial for revealing the intrinsic physical properties of galaxies. We present an analysis of dust attenuation in 18 spectroscopically confirmed star-forming main-sequence galaxies at z = 4.4−5.7 observed with JWST/NIRSpec IFU and NIRCam, selected from the ALPINE and CRISTAL ALMA large programs. We fit the emission-line fluxes from NIRSpec and the broadband photometry from NIRCam with Prospector, using both spatially integrated emission and ∼0.6 kpc pixel-by-pixel measurements. We derive the stellar-to-nebular dust attenuation ratio (f = E(B − V)star/E(B − V)neb) from the SED fits and the Balmer decrement with Hα and Hβ. Although individual galaxies show large scatter, the best-fit value is f=0.51−0.03+0.04 , slightly higher than that measured for local starburst galaxies. We find weak correlations of f with galaxy properties, increasing with higher specific star formation rates, younger stellar ages, and more recent star formation. For the range of E(B − V)star = 0.009−0.15 mag for in our sample, assuming f = 1 (often adopted in high-redshift studies) instead of f = 0.51 leads to the underestimation of line luminosities and ionizing photon production efficiency ξion by ∼3%−36% and ∼4​​​​​​%−46%, respectively. Finally, total stellar masses estimated from spatially integrated SED fits with delayed-τ star formation histories are systematically smaller than the sums of pixel-by-pixel SED fits by a median of ∼0.26 dex, likely because the integrated fits are biased toward luminous young stellar populations.