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BACKGROUND: Many law enforcement agencies across the United States equip their officers with the life-saving drug naloxone to reverse the effects of an opioid overdose. Although officers can be effectively trained to administer naloxone, and hundreds of law enforcement agencies carry naloxone to reverse overdoses, little is known about what happens on scene during an overdose call for service from an officers perspective, including what officers perceive their duties and responsibilities to be as the incident evolves. METHODS: The qualitative study examined officers experiences with overdose response, their perceived roles, and what happens on scene before, during, and after an overdose incident. In-person interviews were conducted with 17 officers in four diverse law enforcement agencies in the United States between January and May 2020. RESULTS: Following an overdose, the officers described that overdose victims are required to go to a hospital or they are taken to jail. Officers also described their duties on scene during and after naloxone administration, including searching the belongings of the person who overdosed and seizing any drug paraphernalia. CONCLUSION: These findings point to a pressing need for rethinking standard operating procedures for law enforcement in these situations so that the intentions of Good Samaritan Laws are upheld and people get the assistance they need without being deterred from asking for future help.

Methods to deliver gene editing agents in vivo as ribonucleoproteins could offer safety advantages over nucleic acid delivery approaches. We report the development and application of engineered DNA-free virus-like particles (eVLPs) that efficiently package and deliver base editor or Cas9 ribonucleoproteins. By engineering VLPs to overcome cargo packaging, release, and localization bottlenecks, we developed fourth-generation eVLPs that mediate efficient base editing in several primary mouse and human cell types. Using different glycoproteins in eVLPs alters their cellular tropism. Single injections of eVLPs into mice support therapeutic levels of base editing in multiple tissues, reducing serum Pcsk9 levels 78% following 63% liver editing, and partially restoring visual function in a mouse model of genetic blindness. In vitro and in vivo off-target editing from eVLPs was virtually undetected, an improvement over AAV or plasmid delivery. These results establish eVLPs as promising vehicles for therapeutic macromolecule delivery that combine key advantages of both viral and nonviral delivery.

AimMost of the carcinogenic pollutants coming from tobacco smoking or other combustion processes tend to accumulate in settled house dust (SHD) over time. This study evaluated the load of these pollutants in smokers and non-smokers' houses from relatively fresh SHD collected in five different districts on the island of Malta.MethodsAn improved, efficient extraction method to obtain three fractions from a 200 mg of SHD was developed. It was validated for the analysis of nicotine and polycyclic aromatic hydrocarbons (PAH) by GC-MS/MS and nicotelline and TSNA by LC-MS/MS. Kruskal-Wallis H tests were used to evaluate differences across districts, while a Mann-Whitney U test was used to check differences between smokers and non-smokers' houses. Diagnostic ratios were used to evaluate the carcinogenicity of PAH in SHD in Malta.ResultsFor all analytes, no statistical difference was observed across different districts, but, in smokers' houses, 97.9% of the total concentration of all target analytes found in SHD is nicotine, 0.1% is TSNA, and 2.0% is PAH. In non-smokers' houses, nicotine represents 16.8% of the load, while 0.4% and 82.8% are TSNA and PAH, respectively. The carcinogenicity of the PAH mixture in Maltese SHD, expressed as the mean benzo(a)pyrene equivalent (BaPeq) is 371 ng/g.ConclusionIndoor activities, ventilation practices, and infiltration of outdoor pollutants contribute to a complex SHD composition. Although the BaPeq is on the lower end of carcinogenicity, the effects of a mixture including tobacco-related potent carcinogens in SHD are largely unknown. In view of indoor, continuous exposure to SHD through several pathways, further research is warranted.

Although beginning to emerge, multiarticulate upper limb prostheses for children remain sparse despite the continued advancement of mechatronic technologies that have benefited adults with upper limb amputations. Upper limb prosthesis research is primarily focused on adults, even though rates of pediatric prosthetic abandonment far surpass those seen in adults. The implicit goal of a prosthesis is to provide effective functionality while promoting healthy social interaction. Yet most current pediatric devices offer a single degree of freedom open/close grasping function, a stark departure from the multiple grasp configurations provided in advanced adult devices. Although comparable child-sized devices are on the clinical horizon, understanding how to effectively translate these technologies to the pediatric population is vital. This includes exploring grasping movements that may provide the most functional benefits and techniques to control the newly available dexterity. Currently, no dexterous pediatric research platforms exist that offer open access to hardware and programming to facilitate the investigation and provision of multi-grasp function. Our objective was to deliver a child-sized multi-grasp prosthesis that may serve as a robust research platform. In anticipation of an open-source release, we performed a comprehensive set of benchtop and functional tests with common household objects to quantify the performance of our device. This work discusses and evaluates our pediatric-sized multiarticulate prosthetic hand that provides 6 degrees of actuation, weighs 177 g and was designed specifically for ease of implementation in a research or clinical-research setting. Through the benchtop and validated functional tests, the pediatric hand produced grasping forces ranging from 0.424-7.216 N and was found to be comparable to the functional capabilities of similar adult devices. As mechatronic technologies advance and multiarticulate prostheses continue to evolve, translating many of these emerging technologies may help provide children with more useful and functional prosthesis options. Effective translation will inevitably require a solid scientific foundation to inform how best to prescribe advanced prosthetic devices and control systems for children. This work begins addressing these current gaps by providing a much-needed research platform with supporting data to facilitate its use in laboratory and clinical research settings.

The most important tobacco-specific nitrosamine found in cigarette smoke and formed in ageing smoke after cigarettes are extinguished is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). It is formed from nitrosation of nicotine, under particular conditions both in indoor and outdoor environments. NNK has been classified as a potent lung carcinogen which is expected to be found primarily in the particle-phase and to be stable in particulate matter. In this study tests have been carried out to show that a bisulfate-treated filter is more efficient than an untreated filter to collect both nicotine and NNK, and that the latter is stable in outdoor particulate matter. To characterize NNK in the outdoor environment, airborne samples were collected from 11 cities in USA, UK, Hong Kong and Malta with characteristics varying from low to high population densities and from urban to suburban to rural, and with desert characteristics and distinct climates. It has been shown that airborne particle + gas phase nicotine and particle-phase NNK behave in a linearly correlated manner. A seasonal analysis was carried out on a subset of data available from five sites in California, where the load of NNK in PM10 is driven by long range transport of the air masses passing over densely populated cities. In the winter season, the load of NNK in PM is higher than in summer in a statistically significant manner. The contamination of PM with NNK shows variability, but is observed at all sites. This paper highlights the potential risk of chronic exposure to NNK in particulate matter by the inhalation pathway.

Biomarkers for the use of electronic nicotine delivery systems (ENDS) are desirable for studies of the health effects of electronic cigarettes and related devices. However, the aerosols inhaled from these devices do not contain substances that are unique to this class of products, i.e., substances that are not present in cigarette smoke or those that do not have common environmental or dietary sources. Consequently, identifying selective biomarkers for ENDS use remains a challenge. If co-use of conventional tobacco products can be definitively ruled out, then nicotine and its metabolites are suitable for assessing exposure. Self-reports from questionnaires are often used to obtain information on product use. But self-reports may not always be accurate, and are not amenable to obtaining quantitative information on exposure. An alternative approach is to use selective biomarkers for conventional tobacco products to definitively rule out their use. In this article, we describe two new LC-MS/MS methods for the minor tobacco alkaloids anabasine, anatabine, nicotelline, anatalline, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific nitrosamine metabolite, all biomarkers that are selective for the use of conventional tobacco products. Applications of these biomarkers in studies of ENDS use and dual use of ENDS and conventional tobacco products are also discussed.

Introduction: Conducted electrical weapons, commonly known by their proprietary eponym, TASER, are frequently used by law enforcement. A review of the literature yielded descriptions of taser barb removal from soft tissue and surgical intervention for barbs lodged in sensitive areas such as the eye and head, but not from other osseous sites.Case Report: We report the case of a 30-year-old male transferred from another hospital with a taser dart embedded in his clavicle. Prior attempts at bedside removal had been unsuccessful. We describe bedside removal of the taser barb from bone using local anesthesia and simple fulcrum technique.Conclusion: We describe a novel fulcrum technique for removal of a taser dart embedded in bone. This is a reasonable technique to attempt in patients with involvement of superficial osseous structures to avoid operative intervention.

Copper is known to have toxic effects on bacterial growth. This study aimed to determine the influence of copper ions on Oleidesulfovibrio alaskensis G20 biofilm formation in a lactate-C medium supplemented with variable copper ion concentrations. OA G20, when grown in media supplemented with high copper ion concentrations of 5, 15, and 30 µM, exhibited inhibited growth in its planktonic state. Conversely, under similar copper concentrations, OA G20 demonstrated enhanced biofilm formation on glass coupons. Microscopic studies revealed that biofilms exposed to copper stress demonstrated a change in cellular morphology and more accumulation of carbohydrates and proteins than controls. Consistent with these findings, sulfur (dsrA, dsrB, sat, aprA) and electron transport (NiFeSe, NiFe, ldh, cyt3) genes, polysaccharide synthesis (poI), and genes involved in stress response (sodB) were significantly upregulated in copper-induced biofilms, while genes (ftsZ, ftsA, ftsQ) related to cellular division were negatively regulated compared to controls. These results indicate that the presence of copper ions triggers alterations in cellular morphology and gene expression levels in OA G20, impacting cell attachment and EPS production. This adaptation, characterized by increased biofilm formation, represents a crucial strategy employed by OA G20 to resist metal ion stress.

Current therapies targeting the human epidermal growth factor receptor (HER) family, including monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs), are limited by drug resistance and systemic toxicities. Antibody–drug conjugates (ADCs) are one of the most rapidly expanding classes of anti-cancer therapeutics with 13 presently approved by the FDA. Importantly, ADCs represent a promising therapeutic option with the potential to overcome traditional HER-targeted therapy resistance by delivering highly potent cytotoxins specifically to HER-overexpressing cancer cells and exerting both mAb- and payload-mediated antitumor efficacy. The clinical utility of HER-targeted ADCs is exemplified by the immense success of HER2-targeted ADCs including trastuzumab emtansine and trastuzumab deruxtecan. Still, strategies to improve upon existing HER2-targeted ADCs as well as the development of ADCs against other HER family members, particularly EGFR and HER3, are of great interest. To date, no HER4-targeting ADCs have been reported. In this review, we extensively detail clinical-stage EGFR-, HER2-, and HER3-targeting monospecific ADCs as well as novel clinical and pre-clinical bispecific ADCs (bsADCs) directed against this receptor family. We close by discussing nascent trends in the development of HER-targeting ADCs, including novel ADC payloads and HER ligand-targeted ADCs.

Neurodevelopmental outcomes for preschool-age children in the United States with in utero Zika virus (ZIKV) exposure have not yet been reported. We performed a case-control study to assess whether children exposed in utero to ZIKV have abnormal neurodevelopment at age 4–5 years compared to unexposed controls. Thirteen ZIKV-exposed cases that did not have microcephaly or other specific features of congenital Zika syndrome and 12 controls were evaluated between ages 4–5 years. Child neurodevelopment was assessed using the Pediatric Evaluation of Disability Inventory, Behavior Rating Inventory of Executive Function, Peabody Picture Vocabulary Test, Bracken School Readiness Assessment (BSRA), and Movement Assessment Battery for Children (MABC). Caregivers answered questions on the child’s medical history and family demographics. Cases and controls were evaluated at mean (SD) ages 4.9 (0.3) and 4.8 (0.4) years, respectively. Caregivers reported more behavior and mood problems in cases than controls. MABC scores showed more gross and fine motor coordination difficulties among cases than controls. Controls trended towards higher performance on concepts underlying school readiness on BSRA. Three cases had a diagnosis of autism spectrum disorder or global developmental delay. Continued follow-up through school age for children with prenatal ZIKV exposure is needed to understand the impact of in utero ZIKV exposure on motor coordination, cognition, executive function, and academic achievement.

A reliable and efficient rail track defect detection system is essential for maintaining rail track integrity and avoiding safety hazards and financial losses. Eddy current (EC) testing is a non-destructive technique that can be employed for this purpose. The trade-off between spatial resolution and lift-off should be carefully considered in practical applications to distinguish closely spaced cracks such as those caused by rolling contact fatigue (RCF). A multi-channel eddy current sensor array has been developed to detect defects on rails. Based on the sensor scanning data, defect reconstruction along the rails is achieved using an inverse algorithm that includes both direct and iterative approaches. In experimental evaluations, the EC system with the developed sensor is used to measure defects on a standard test piece of rail with a probe lift-off of 4–6 mm. The reconstruction results clearly reveal cracks at various depths and spacings on the test piece.

Keratoconus is a bilateral ocular condition characterized by irregularities and the thinning of the cornea. Decreased central corneal thickness is a hallmark of the condition, and numerous genes have played a role in altering corneal thickness and the subsequent development of keratoconus. Variants in the structural and regulatory genes of the extracellular matrix have been highly associated with keratoconus, as well as with pectus excavatum, a chest wall deformity commonly seen in connective tissue disorders. This report describes a patient with a c.1720-11T>A intronic variant in the collagen-encoding gene, COL5A1, who was diagnosed with early-onset keratoconus and demonstrated a significant pectus excavatum. This report associates a COL5A1 variant with these seemingly unrelated phenotypic associations, further advancing the literature on the topic.

Traditionally, 4-H agents have been communicating with stakeholders through newsletters; either in print or online. 4-H agents have used social media as an additional tool to communicate with their stakeholders since its introduction. Social media communication can help maintain or increase stakeholder involvement in the 4-H program because a large percentage of the population is active on social media. Using Uses and Gratifications Theory and Diffusion of Innovations Theory as frameworks, this study sought to determine how Florida 4-H agents engaged with their stakeholder audiences using social media, and vice versa. The uses and gratifications motivations for engaging in media were used to understand what motivations were used to engage their audience and what type of posts (according to motivation) stakeholders were engaged in most. The diffusion of innovations innovation-decision process helped to understand the audiences' decision to engage in posts dependent upon the motivation used. The results of this study concluded the selected 4-H programs differed in the content that they posted but the 4-H stakeholders did not differ in how they engaged in their respective programs posts.

Background: Ongoing evidence of trauma in nurses, beginning in nursing school, requires educators to take a trauma-informed approach to teaching and learning to minimize re-traumatization and to ultimately achieve socially-just student outcomes. Methods: The purpose of this study was to evaluate the outcomes of trauma-informed educational practices (TIEP) on nursing students and the trauma-informed climate in the classroom using an intervention comparison group pre-posttest design. Results: Secondary traumatic stress (STS) scores declined for both groups pre- to post-test. There was a statistically significant difference in STS change scores between intervention and comparison groups (p < 0.05), but not in the direction hypothesized. Conclusion: Findings from this study indicate that other factors in the nursing classroom might have contributed significantly to a reduction in STS. In addition to outcomes, future TIEP evaluations should explore student awareness and experiences of trauma, resilience, professional preparation, and learning outcomes in the classroom setting.

Abstract The external globus pallidus (GPe) coordinates action-selection through GABAergic projections throughout the basal ganglia. GPe arkypallidal (arky) neurons project exclusively to the dorsal striatum, which regulates goal-directed and habitual seeking. However, the role of GPe arky neurons in reward-seeking remains unknown. Here, we identified that a majority of arky neurons target the dorsolateral striatum (DLS). Using fiber photometry, we found that arky activities were higher during random interval (RI; habit) compared to random ratio (RR; goal) operant conditioning. Support vector machine analysis demonstrated that arky neuron activities have sufficient information to distinguish between RR and RI behavior. Genetic ablation of this arkyGPe→DLS circuit facilitated a shift from goal-directed to habitual behavior. Conversely, chemogenetic activation globally reduced seeking behaviors, which was blocked by systemic D1R agonism. Our findings reveal a role of this arkyGPe→DLS circuit in constraining habitual seeking in male mice, which is relevant to addictive behaviors and other compulsive disorders.

Chronic consequences of mild traumatic brain injury (mTBI) are heterogeneous, but may be treatable with targeted medical and rehabilitation interventions. A biological signature for the likelihood of response to therapy (i.e., ?predictive? biomarkers) would empower personalized medicine post-mTBI. The purpose of this study was to correlate pre-intervention blood biomarker levels and the likelihood of response to targeted interventions for patients with chronic issues attributable to mTBI. Patients with chronic symptoms and/or disorders secondary to mTBI >3 months previous (104 days to 15 years; n?=?74) were enrolled. Participants completed pre-intervention assessments of symptom burden, comprehensive clinical evaluation, and blood-based biomarker measurements. Multi-domain targeted interventions for specific symptoms and impairments across a 6-month treatment period were prescribed. Participants completed a follow-up testing after the treatment period. An all-possible model's backward logistic regression was built to identify predictors of improvement in relation to blood biomarker levels before intervention. The minimum clinically important difference (MCID) of the change score (post-intervention subtracted from pre-intervention) for the Post-Concussion Symptom Scale (PCSS) to identify treatment responders from non-responders was the primary outcome. The MCID for total PCSS score was 10. The model to predict change in PCSS score over the 6-month intervention was significant (R2?=?0.09; p?=?0.01) and identified ubiquitin C-terminal hydrolase L1 (odds ratio [OR]?=?2.53; 95% confidence interval [CI], 1.18?5.46; p?=?0.02) and hyperphosphorylated tau (p-tau; OR?=?0.70; 95% CI, 0.51?0.96; p?=?0.03) as significant predictors of symptom improvement beyond the PCSS MCID. In this cohort of chronic TBI subjects, blood biomarkers before rehabilitation intervention predicted the likelihood of response to targeted therapy for chronic disorders post-TBI.

Abstract High throughput drug screening is an established approach to investigate tumor biology and identify therapeutic leads. Traditional platforms use two-dimensional cultures which do not accurately reflect the biology of human tumors. More clinically relevant model systems such as three-dimensional tumor organoids can be difficult to scale and screen. Manually seeded organoids coupled to destructive endpoint assays allow for the characterization of treatment response, but do not capture transitory changes and intra-sample heterogeneity underlying clinically observed resistance to therapy. We present a pipeline to generate bioprinted tumor organoids linked to label-free, time-resolved imaging via high-speed live cell interferometry (HSLCI) and machine learning-based quantitation of individual organoids. Bioprinting cells gives rise to 3D structures with unaltered tumor histology and gene expression profiles. HSLCI imaging in tandem with machine learning-based segmentation and classification tools enables accurate, label-free parallel mass measurements for thousands of organoids. We demonstrate that this strategy identifies organoids transiently or persistently sensitive or resistant to specific therapies, information that could be used to guide rapid therapy selection.

Microbial diversity estimation involves extracting nucleic acids from intricate sample matrices. Preparing nucleic acid samples is time-consuming, necessitating effective cell lysis and obtaining pure, inhibitor-free nucleic acid purifications before further use. An automated system offers advantages for field deployment due to its ease of use and quick autonomous results. This is especially beneficial for rapid measurement of in situ microbial diversity in remote areas. Our study aimed to assess microbial diversity of Yellowstone hot springs using a field-deployable lab in a resource-limited remote setting and demonstrate on-site nucleic acid sample processing and sequencing. We collected microbial mat and sediment samples from several Yellowstone National Park hot springs, focusing on the Five Sister Springs (FSS), spring LNN010, and Octopus Spring (OS). The samples were processed for DNA extraction on-site and further sequenced in the lab for microbial diversity. In addition, DNA extracted from one sample was sequenced and analyzed on-site as proof-of-concept. Using either Illumina or Oxford Nanopore Technology sequencing, we found similar microbial diversities. Bacteria (over 90%) were predominant at the FSS and OS sites, with archaea accounting for less than 10%. Metagenomic results were taxonomically categorized based on the closest known organism with a sequenced genome. The dominant archaeal community member was Candidatus Caldiarchaeum subterraneum, and among bacteria, Roseiflexus sp. RS-1 was abundant in mat samples. Interestingly, Bacterium HR17 was also frequently found, suggesting the need for more research on this newly recognized bacterial community member. The presence of Bacterium HR17 in these hot springs suggests its potential role in nitrogen cycling, informing both ecological understanding and industrial potential. This pioneering study assessed the microbiome of Yellowstone hot springs in about 8-9 hours using an automated system for nucleic acid extraction. By its deployment, the system’s value in elucidating the microbial diversity of extreme environments without the need to bring samples to the lab for processing had been highlighted. Sample processing and sequencing had been included in the benefits of the field-deployable lab, and the Nanopore platform had been utilized.

Despite the policy recommendation and effectiveness of administering the hepatitis B birth-dose vaccine (HepB-BD) to newborns to prevent mother-to-child hepatitis B transmission, timely uptake remains an issue. Countries adopting the HepB-BD to their national immunization schedule report programmatic challenges to administering the vaccine within the recommended 24-hour window after delivery. Further, while the World Health Organization recommends streamlining three birth-dose vaccines (HepB-BD, BCG, and OPV0), scarce Sub-Saharan(SSA)-based literature reports on a streamlined and timely approach to birth-dose vaccines. As more SSA countries adopt the new birth-dose vaccine to their immunization schedules, a systematically developed implementation strategy-Vaccination of Newborns-Innovative Strategies to Hasten Birth-Dose vaccines' delivery (VANISH-BD)-will facilitate the adoption and implementation of timely birth-dose vaccine uptake. In this paper, we describe the development of the implementation strategy using intervention mapping, an evidence-based and theory-driven approach. We report on the development of our intervention, beginning with the needs assessment based in Kinshasa Province, Democratic Republic of the Congo (DRC), informing step 1 of intervention mapping. The intervention is contextually relevant, locally produced, sustainable, and designed to improve timely birth-dose vaccine uptake in the DRC. We intend to inform future implementers about improving timely and streamlined birth-dose vaccine uptake and for VANISH-BD to be adapted for similar contexts.

Recovery following spinal surgery can be challenging, particularly concerning postoperative pain management. The first-line treatment for postoperative pain is opioid analgesia, but opioid overuse can lead to adverse effects. Liposomal bupivacaine (LB), an extended-release local anesthetic, has shown promise as a method of enhancing postoperative pain control. This systematic review aims to provide a comprehensive evaluation of the effectiveness of LB in improving postoperative outcomes after spinal surgery. Following the PRISMA guidelines, 18 studies met inclusion criteria and were evaluated for pain, opioid consumption, length of stay (LOS), and adverse events. Six studies showed no significant difference between treatment groups in all three major outcomes. Only two studies showed statistically improved pain control, opioid use, and LOS with LB. Similarly, another study also demonstrated improved pain control in the LB group; however, there was no significant change in opioid use or LOS. Two other studies also showed significantly improved postoperative pain control after the administration of LB, but the effect lasted only 24 hours after surgery. Three other reports saw a quicker transition off intravenous opioids with LB use, but no difference in total opioid use. Three of the four studies that focused on pediatric populations found improvement in all major outcomes with LB use; the fourth saw no significant difference between treatment groups. Currently, evidence is poor to suggest that LB significantly improves postoperative pain, opioid use, or LOS in adults. However, several patterns were identified that may influence study results: reports performed at military bases have different, more stringent protocols for recovery, and differences in spinal surgeries, some more invasive than others, can lead to different pain levels. The results of this systematic review demonstrate that the addition of LB does not provide improved postoperative pain control after spinal surgery in adults as demonstrated by both randomized controlled trials (RCTs) and the majority of retrospective cohort studies (RCSs). However, the use of LB for spine surgeries may be justified for the pediatric population, but further research is warranted given the limited reports available.

The motor features of Parkinson's disease result from loss of dopaminergic neurons in the substantia nigra with autophagy dysfunction being closely linked to this disease. While a large body of work focusing on protein effectors of autophagy has been reported, regulation of autophagy by lipids has garnered far less attention. Therefore, we sought to identify endogenous lipid molecules that act as signaling mediators of autophagy in differentiated SH-SY5Y cells, a commonly used dopaminergic neuron-like cell model. In order to accomplish this goal, we assessed the role of a fatty acid-binding protein (FABP) family member on autophagy due to its function as an intracellular lipid chaperone. We focused specifically upon FABP5 due to its heightened expression in dopaminergic neurons within the substantia nigra and SH-SY5Y cells. Here, we report that knockdown of FABP5 resulted in suppression of autophagy in differentiated SH-SY5Y cells suggesting the possibility of an autophagic role for an interacting lipid. A lipidomic screen of FABP5-interacting lipids uncovered hits that include 5-oxo-eicosatetraenoic acid (5OE) and its precursor metabolite, arachidonic acid (AA). Additionally, other long-chain fatty acids were found to bind FABP5, such as stearic acid (SA), hydroxystearic acid (HSA), and palmitic acid (PA). The addition of 5OE, SA, and HSA but not AA or PA, led to potent inhibition of autophagy in SH-SY5Y cells. To identify potential molecular mechanisms for autophagy inhibition by these lipids, RNA-Seq was performed which revealed both shared and divergent signaling pathways between the lipid-treated groups. These findings suggest a role for these lipids in modulating autophagy through diverse signaling pathways and could represent novel therapeutic targets for Parkinson's disease.

Plants rely on a diverse rhizobiome to regulate nutrient acquisition and plant health. With increasing severity and frequency of droughts worldwide due to climate change, untangling the relationships between plants and their rhizobiomes is vital to maintaining agricultural productivity and protecting ecosystem diversity. While some plant physiological responses to drought are generally conserved, patterns of root exudation (release of small metabolites shown to influence microbes) and the consequential effects on the plant rhizobiome can differ widely across plant species under drought. To address this knowledge gap, we conducted a greenhouse study using blue grama (Bouteloua gracilis), a drought-tolerant C4 grass native to shortgrass prairie across North American plains, as a model organism to study the effect of increasing drought severity (ambient, mild drought, severe drought) on root exudation and the rhizobiome. Our previous results demonstrated physiological effects of increasing drought severity including an increase in belowground carbon allocation through root exudation and shifts in root exudate composition concurrent with the gradient of drought severity. This work is focused on the rhizobiome community structure using targeted sequencing and found that mild and severe drought resulted in unique shifts in the bacterial + archaeal and fungal communities relative to ambient, non-droughted controls. Specifically, using the change in relative abundance between ambient and drought conditions for each ZOTU as a surrogate for population-scale drought tolerance (e.g., as a response trait), we found that rhizobiome response to drought was non-randomly distributed across the phylogenies of both communities, suggesting that Planctomycetota, Thermoproteota (formerly Thaumarchaeota), and the Glomeromycota were the primary clades driving these changes. Correlation analyses indicated weak correlations between droughted community composition and a select few root exudate compounds previously implicated in plant drought responses including pyruvic acid, D-glucose, and myoinositol. This study demonstrates the variable impacts of drought severity on the composition of the blue grama rhizobiome and provides a platform for hypothesis generation for targeted functional studies of specific taxa involved in plant-microbe drought responses.

Background. To characterize the mechanism of knee injuries among NBA players during the 2010–2020 seasons using video-based analysis. Methods. An injury database of NBA players was queried for knee injuries from the 2006-07 to 2020-21 seasons and cross-referenced with NBA injury reports. Youtube.com was searched to identify available injury footage. The mechanism of knee injury during play was analyzed by three independent reviewers. Non-mechanistic data related to the injury was gathered from news reports and official NBA websites. Results. A total of 2,868 knee injuries occurred in NBA players from 2010 to 2020 seasons; 121 had high quality videos for analysis. The most common mechanism of injury was knee flexion in valgus with internal rotation (27.3%, p

Key Clinical Message We report the first multigenerational family with NFIA‐related disorder from a missense variant. This case highlights the condition's phenotypic variability and the need for genetic testing when an initial diagnosis fails to explain all symptoms.

Abstract Objective: Caregivers require tangible (e.g. food and financial) and intangible resources to provide care to ensure child health, nutrition and development. Intangible resources include beliefs and knowledge, education, self-efficacy, perceived physical health, mental health, healthy stress levels, social support, empowerment, equitable gender attitudes, safety and security and time sufficiency. These intangible caregiver resources are included as intermediate outcomes in nutrition conceptual frameworks yet are rarely measured as part of maternal and child nutrition research or evaluations. To facilitate their measurement, this scoping review focused on understudied caregiver resources that have been measured during the complementary feeding period in low- and lower-middle-income countries. Design: We screened 9,232 abstracts, reviewed 277 full-text articles and included 163 articles that measured caregiver resources related to complementary feeding or the nutritional status of children 6 months to 2 years of age. Results: We identified measures of each caregiver resource, though the number of measures and quality of descriptions varied widely. Most articles (77 %) measured only one caregiver resource, mental health (n 83) and social support (n 54) most frequently. Psychometric properties were often reported for mental health measures, but less commonly for other constructs. Few studies reported adapting measures for specific contexts. Existing measures for mental health, equitable gender attitudes, safety and security and time sufficiency were commonly used; other constructs lacked standardised measures. Conclusions: Measurement of caregiver resources during the complementary feeding period is limited. Measuring caregiver resources is essential for prioritising caregivers and understanding how resources influence child care, feeding and nutrition.

Ostreid herpesvirus 1 (OsHV-1) is one of the most economically important pathogens of Pacific oysters. Understanding the pathogenesis of this virus is critical to developing tools to control outbreaks on shellfish farms. OsHV-1 is genetically related to vertebrate herpesviruses, which have a lytic and a latent stage, with the latent stage capable of being reactivated to the lytic stage. Here, OsHV-1 latency in Pacific oysters was investigated in experimentally and naturally infected oysters. Lytic infection in one-year-old oysters injected with the Tomales Bay strain of OsHV-1 was detectable between 1 and 4 days post-injection (dpi) but was not detectable after 5 dpi. The injected oysters shed 1 × 102 to 1 × 104 DNA copies/ml into the water during the 4-day acute phase. Lytic shedding was not detectable in two-year-old oysters injected similarly with the same strain of OsHV-1; however, the OsHV-1 genome was detectable by qPCR in the adductor muscle, gill, mantle, and hemocytes within the first 3 dpi, after which it became undetectable. No OsHV-1 was detectable in the adductor muscle, gill, or mantle from experimentally infected oysters on days 15 and 21 post-injection or from oysters sampled 9 months after surviving an OsHV-1 mortality event; however, OsHV-1 DNA could be detected in hemocytes of both experimentally infected oysters at 21 dpi and naturally infected oysters using nested PCR. In addition, lytic viral gene transcription was detectable in hemocytes of experimentally infected oysters between 1 and 21 dpi and in hemocytes of naturally infected oysters. Furthermore, OsHV-1 reactivation from latency was induced in experimentally infected oysters at 21 dpi and in naturally infected oysters 12 months after an OsHV-1 outbreak.

Identification of enteric bacteria species by whole genome sequence (WGS) analysis requires a rapid and an easily standardized approach. We leveraged the principles of average nucleotide identity using MUMmer (ANIm) software, which calculates the percent bases aligned between two bacterial genomes and their corresponding ANI values, to set threshold values for determining species consistent with the conventional identification methods of known species. The performance of species identification was evaluated using two datasets: the Reference Genome Dataset v2 (RGDv2), consisting of 43 enteric genome assemblies representing 32 species, and the Test Genome Dataset (TGDv1), comprising 454 genome assemblies which is designed to represent all species needed to query for identification, as well as rare and closely related species. The RGDv2 contains six Campylobacter spp., three Escherichia/Shigella spp., one Grimontia hollisae, six Listeria spp., one Photobacterium damselae, two Salmonella spp., and thirteen Vibrio spp., while the TGDv1 contains 454 enteric bacterial genomes representing 42 different species. The analysis showed that, when a standard minimum of 70% genome bases alignment existed, the ANI threshold values determined for these species were ≥95 for Escherichia/Shigella and Vibrio species, ≥93% for Salmonella species, and ≥92% for Campylobacter and Listeria species. Using these metrics, the RGDv2 accurately classified all validation strains in TGDv1 at the species level, which is consistent with the classification based on previous gold standard methods.

Background: We aimed to report the preliminary xylazine prevalence among people who inject drugs (PWID) treated at a student-run free clinic in Miami, FL, USA and to identify characteristics associated with screening positive for xylazine. Methods: A retrospective chart review of 59 patients presenting to a syringe services program (SSP) clinic in was conducted between April 27th and August 17th, 2023. We measured presence of xylazine with rapid visual immunoassay strips on patient urine samples. Results: Xylazine was present in 55.9 % (33/59) of urine samples including 2 without detected opioids. Xylazine presence was significantly associated with unsheltered homelessness (p = 0.018), presence of wound(s) (p = 0.008), and testing positive for hepatitis C antibody (p = 0.014), fentanyl (p = 0.005) and MDMA (p = 0.002). Conclusions: A high prevalence of xylazine in the Southeastern United States furthers evidence of the geographical spread of xylazine and rapidly evolving illicit drug supply. Widespread xylazine screening is urgently needed to inform people who inject drugs and to studyinterventions to minimize harms associated with xylazine.

The soil management assessment framework (SMAF) has been widely used as a tool to quantify soil health. However, SMAF was developed using data from only a few climate conditions in the United States and regional verification is often suggested. We evaluated SMAF's short-term performance in a thermic/hyperthermic region, aiming to 1) evaluate the sensitivity of SMAF scores to changes in individual soil properties and 2) quantify soil health changes using SMAF. Treatments include two levels of summer crop and two levels of tillage in an annually planted wheat system. SMAF soil health metrics were measured for Burleson clay soil (BC site) and Parrita sandy clay loam soil (PSCL site) for 0–5 cm soil depth. At the BC site, βgluc and SOC SMAF scores displayed no statistical differences when compared to their respective soil properties. βgluc measurement also helped to highlight the treatment difference observed for wheat yield. This suggests that scoring curves of βgluc used in SMAF may need to be modified, especially for clayey soils. The results also show that SMAF scores were not correlated with wheat yield at both sites, suggesting that multiple year data may be needed to understand this relationship. Overall, in a thermic region, SMAF was found to be helpful to understand short-term soil health status. However, due to clay correction in SMAF algorithm, SMAF scores can show lower sensitivity in the clayey soils of these thermic regions.

Water is not only essential to sustain life on Earth, but also is a crucial resource for long-duration deep space exploration and habitation. Current systems in space rely on the resupply of water from Earth, however, as missions get longer and move farther away from Earth, resupply will no longer be a sustainable option. Thus, the development of regenerative reclamation water systems through which useable water can be recovered from “waste streams” (i.e., used waters) is sorely needed to further close the loop in space life support systems. This review presents the origin and characteristics of different used waters generated in space and discusses the intrinsic challenges of developing suitable technologies to treat such streams given the unique constrains of space exploration and habitation (e.g., different gravity conditions, size and weight limitations, compatibility with other systems, etc.). In this review, we discuss the potential use of biological systems, particularly biofilms, as possible alternatives or additions to current technologies for water reclamation and waste treatment in space. The fundamentals of biofilm reactors, their advantages and disadvantages, as well as different reactor configurations and their potential for use and challenges to be incorporated in self-sustaining and regenerative life support systems in long-duration space missions are also discussed. Furthermore, we discuss the possibility to recover value-added products (e.g., biomass, nutrients, water) from used waters and the opportunity to recycle and reuse such products as resources in other life support subsystems (e.g., habitation, waste, air, etc.).