Structure of a Human Monoclonal Antibody in Complex with Outer Surface Protein C of the Lyme Disease Spirochete, Borreliella burgdorferi.

Lyme disease is a tick-borne, multisystem infection caused by the spirochete Borreliella burgdorferi. Although Abs have been implicated in the resolution of Lyme disease, the specific B cell epitopes targeted during human infections remain largely unknown. In this study, we characterized and defined the structural epitope of a patient-derived bactericidal monoclonal IgG (B11) against outer surface protein C (OspC), a homodimeric lipoprotein necessary for B. burgdorferi tick-mediated transmission and early-stage colonization of vertebrate hosts. High-resolution epitope mapping was accomplished through hydrogen deuterium exchange-mass spectrometry and X-ray crystallography. Structural analysis of B11 Fab-OspCA complexes revealed the B11 Fabs associated in a 1:1 stoichiometry with the lateral faces of OspCA homodimers such that the Abs are essentially positioned perpendicular to the spirochete's outer surface. B11's primary contacts reside within the membrane-proximal regions of α-helices 1 and 6 and adjacent loops 5 and 6 in one OspCA monomer. In addition, B11 spans the OspCA dimer interface, engaging opposing α-helix 1', α-helix 2', and loop 2-3' in the second OspCA monomer. The B11-OspCA structure is reminiscent of the recently solved mouse transmission blocking monoclonal IgG B5 in complex with OspCA, indicating a mode of engagement with OspC that is conserved across species. In conclusion, we provide a detailed insight into the interaction between a functional human Ab and an immunodominant Lyme disease Ag long considered an important vaccine candidate.

The Impact of Patient Assaults and Aggressive Behaviors on Nursing Personnel's Stress, Well-being, and Intention to Leave Post-COVID-19 Pandemic.

AIM: To describe and compare the prevalence of assaults and aggressive patient behavior among frontline staff in behavioral health (BH), medical-surgical (MS), and emergency department (ED) settings and examine the impact on staff health, work stress, work engagement, and intent to leave their position. BACKGROUND: Patient verbal and physical assaults have significant staff consequences, including decreased work productivity, increased burnout, job dissatisfaction, absenteeism, turnover, and intentions to leave. METHODS: Using a descriptive cross-sectional design, data were collected from a sample of 432 frontline staff working in ED, BH, and MS settings across 3 healthcare systems. RESULTS: The majority of frontline staff (74%) reported experiencing verbal aggression often/frequently, significantly impacting their mental health, work engagement, stress levels, and intent to leave. All 3 specialty groups reported a significant increase in verbal/psychological assaults and physical assaults since the pandemic's onset. CONCLUSION: The COVID-19 pandemic had a significant impact on assaultive/aggressive behaviors. Nurse leaders must strategize on methods to decrease the normalization of violence against healthcare workers and support research aimed at evidence-based interventions to reduce such incidences of violence and ensure the well-being of healthcare workers.

Factors Affecting Peripheral Intravenous Catheter Placement During Pediatric Trauma Resuscitation.

INTRODUCTION: Intravenous access is required for resuscitation of injured patients but may be delayed in children because of challenges associated with peripheral intravenous (PIV) catheter placement. Early identification of factors predisposing patients to difficult PIV placement can assist in deciding strategies for timely intravenous access. METHODS: We conducted a retrospective, video-based review of injured children and adolescents treated between April 2018 and May 2019. Patient demographic, physiological, injury, and resuscitation characteristics were obtained from the patient record, including age, race, weight, injury type, Injury Severity Score, initial systolic blood pressure, initial Glasgow Coma Score, intubation status, activation level, and presence of prearrival notification. Video review was used to determine the time to PIV placement, the number of attempts required, the purpose for additional access, and the reason for abandonment of PIV placement. Multivariable regressions were used to determine factors associated with successful placement. RESULTS: During the study period, 154 consented patients underwent attempts at PIV placement in the trauma bay. Placement was successful in 139 (90.3%) patients. Older patients (OR [odds ratio]: 0.9, 95% confidence interval [CI]: 0.9, 0.9) and patients who required the highest level activation response (OR: 0.0, 95% CI: 0.0, 0.3) were less likely to have an attempt at PIV placement abandoned. Children with nonblunt injuries (OR: 11.6, 95% CI: 1.3, 119.2) and pre-existing access (OR: 39.6, 95% CI: 7.0, 350.6) were more likely to have an attempt at PIV placement abandoned. Among patients with successful PIV placement, the time required for establishing PIV access was faster as age increased (-0.5 s, 95% CI: -1.1, -0.0). CONCLUSIONS: Younger age was associated with abandonment of PIV attempts and, when successful, increased time to placement. Strategies to improve successful PIV placement and alternate routes of access should be considered early to prevent treatment delays in younger children.

Language-specific phonological skills and the relationship with reading accuracy in Sylheti-English sequential bilinguals.

This study investigated the influence of first language (L1) phonology on second language (L2) early reading skills in Sylheti-English bilinguals (N = 58; 48% girls; British Bangladeshi) and their monolingual-English peers (N = 43; 45% girls; 96% White British, 4% multiethnic British) in a diaspora context. Language-specific phonological awareness and nonword repetition were tested at two time points (6;2-7;8 years-old). At Time 1, the bilinguals had lower productive accuracy for phonological sequences that violated their L1 phonology (d = .56; .84), and these skills accounted for a significant amount of variance in their reading accuracy. At Time 2, the language-specific effects were no longer present. These findings highlight the importance of considering language structure in multilingual early literacy development.

Personal Protective Equipment Adherence of Pediatric Resuscitation Team Members During the COVID-19 Pandemic.

STUDY OBJECTIVE: During the COVID-19 pandemic, health care workers have had the highest risk of infection among essential workers. Although personal protective equipment (PPE) use is associated with lower infection rates, appropriate use of PPE has been variable among health care workers, even in settings with COVID-19 patients. We aimed to evaluate the patterns of PPE adherence during emergency department resuscitations that included aerosol-generating procedures. METHODS: We conducted a retrospective, video-based review of pediatric resuscitations involving one or more aerosol-generating procedures during the first 3 months of the COVID-19 pandemic in the United States (March to June 2020). Recommended adherence (complete, inadequate, absent) with 5 PPE items (headwear, eyewear, masks, gowns, gloves) and the duration of potential exposure were evaluated for individuals in the room after aerosol-generating procedure initiation. RESULTS: Among the 345 health care workers observed during 19 resuscitations, 306 (88.7%) were nonadherent (inadequate or absent adherence) with the recommended use of at least 1 PPE type at some time during the resuscitation, 23 (6.7%) of whom had no PPE. One hundred and forty health care workers (40.6%) altered or removed at least 1 type of PPE during the event. The aggregate time in the resuscitation room for health care workers across all events was 118.7 hours. During this time, providers had either absent or inadequate eyewear for 46.4 hours (39.1%) and absent or inadequate masks for 35.2 hours (29.7%). CONCLUSION: Full adherence with recommended PPE use was limited in a setting at increased risk for SARS-CoV-2 virus aerosolization. In addition to ensuring appropriate donning, approaches are needed for ensuring ongoing adherence with PPE recommendations during exposure.

A Functional riboSNitch in the 3' Untranslated Region of FKBP5 Alters MicroRNA-320a Binding Efficiency and Mediates Vulnerability to Chronic Post-Traumatic Pain.

Previous studies have shown that common variants of the gene coding for FK506-binding protein 51 (FKBP5), a critical regulator of glucocorticoid sensitivity, affect vulnerability to stress-related disorders. In a previous report, FKBP5 rs1360780 was identified as a functional variant because of its effect on gene methylation. Here we report evidence for a novel functional FKBP5 allele, rs3800373. This study assessed the association between rs3800373 and post-traumatic chronic pain in 1607 women and men from two ethnically diverse human cohorts. The molecular mechanism through which rs3800373 affects adverse outcomes was established via in silico, in vivo, and in vitro analyses. The rs3800373 minor allele predicted worse adverse outcomes after trauma exposure, such that individuals with the minor (risk) allele developed more severe post-traumatic chronic musculoskeletal pain. Among these individuals, peritraumatic circulating FKBP5 expression levels increased as cortisol and glucocorticoid receptor (NR3C1) mRNA levels increased, consistent with increased glucocorticoid resistance. Bioinformatic, in vitro, and mutational analyses indicate that the rs3800373 minor allele reduces the binding of a stress- and pain-associated microRNA, miR-320a, to FKBP5 via altering the FKBP5 mRNA 3'UTR secondary structure (i.e., is a riboSNitch). This results in relatively greater FKBP5 translation, unchecked by miR-320a. Overall, these results identify an important gene-miRNA interaction influencing chronic pain risk in vulnerable individuals and suggest that exogenous methods to achieve targeted reduction in poststress FKBP5 mRNA expression may constitute useful therapeutic strategies.SIGNIFICANCE STATEMENTFKBP5 is a critical regulator of the stress response. Previous studies have shown that dysregulation of the expression of this gene plays a role in the pathogenesis of chronic pain development as well as a number of comorbid neuropsychiatric disorders. In the current study, we identified a functional allele (rs3800373) in the 3'UTR of FKBP5 that influences vulnerability to chronic post-traumatic pain in two ethnic cohorts. Using multiple complementary experimental approaches, we show that the FKBP5 rs3800373 minor allele alters the secondary structure of FKBP5 mRNA, decreasing the binding of a stress- and pain-associated microRNA, miR-320a. This results in relatively greater FKBP5 translation, unchecked by miR-320a, increasing glucocorticoid resistance and increasing vulnerability to post-traumatic pain.

Contrasting Nitrogen Fate in Watersheds Using Agricultural and Water Quality Information.

Surplus nitrogen (N) estimates, principal component analysis (PCA), and end-member mixing analysis (EMMA) were used in a multisite comparison contrasting the fate of N in diverse agricultural watersheds. We applied PCA-EMMA in 10 watersheds located in Indiana, Iowa, Maryland, Nebraska, Mississippi, and Washington ranging in size from 5 to 1254 km with four nested watersheds. Watershed Surplus N was determined by subtracting estimates of crop uptake and volatilization from estimates of N input from atmospheric deposition, plant fixation, fertilizer, and manure for the period from 1987 to 2004. Watershed average Surplus N ranged from 11 to 52 kg N ha and from 9 to 32% of N input. Solute concentrations in streams, overland runoff, tile drainage, groundwater (GW), streambeds, and the unsaturated zone were used in the PCA-EMMA procedure to identify independent components contributing to observed stream concentration variability and the end-members contributing to streamflow and NO load. End-members included dilute runoff, agricultural runoff, benthic-processing, tile drainage, and oxic and anoxic GW. Surplus N was larger in watersheds with more permeable soils (Washington, Nebraska, and Maryland) that allowed greater infiltration, and oxic GW was the primary source of NO load. Subsurface transport of NO in these watersheds resulted in some removal of Surplus N by denitrification. In less permeable watersheds (Iowa, Indiana, and Mississippi), NO was rapidly transported to the stream by tile drainage and runoff with little removal. Evidence of streambed removal of NO by benthic diatoms was observed in the larger watersheds.

Speech perception and production by sequential bilingual children: a longitudinal study of voice onset time acquisition.

The majority of bilingual speech research has focused on simultaneous bilinguals. Yet, in immigrant communities, children are often initially exposed to their family language (L1), before becoming gradually immersed in the host country's language (L2). This is typically referred to as sequential bilingualism. Using a longitudinal design, this study explored the perception and production of the English voicing contrast in 55 children (40 Sylheti-English sequential bilinguals and 15 English monolinguals). Children were tested twice: when they were in nursery (52-month-olds) and 1 year later. Sequential bilinguals' perception and production of English plosives were initially driven by their experience with their L1, but after starting school, changed to match that of their monolingual peers.

Assessment tool items for addressing physician-patient communication and reducing health care risk factors across multiple enterprise risk management domains.

Expertise in physician-patient communication is a primary outcome measure for physicians. We evaluated residents' communication behaviors with clinic patients following an educational intervention as measured by the Communication Assessment Tool (CAT). Thirty-five internal medicine residents were assessed by patients using the CAT for 3 months before and after the educational intervention. The intervention included a simulated, videotaped patient encounter, mock CAT, and preceptor coaching during video review. The primary outcome was the percentage of CAT items receiving an "excellent" rating from patients before and after the intervention. Research results were compared to previously published CAT studies. Within-resident improvement in the percentage of excellent ratings was small with median changes between 0 and 3 percentage points. Compared to previously published studies, similar results were found for the highest and lowest-scored communication items. Many clinical encounters are time-limited, and physicians do not pursue time-consuming conversations that could reduce health care risk. This data and other published studies suggest seven communication items taking the most time to complete (i.e., shared decision-making) were items demonstrating little or no improvement. This study identified clinical performance risk factors applicable to the Enterprise Risk Management Framework that could impact complication and readmission rates if addressed by changes in physician-patient communication.

Synergizing Safety: A Customized Approach to Curtailing Unplanned Extubations through Shared Decision-making in the NICU.

Background: Unplanned Extubation (UE) remains an important patient safety issue in the Neonatal Intensive Care Unit. Our SMART AIM was to decrease the rate of UE by 10% from the baseline from January to December 2022 by emphasizing collaboration among healthcare professionals and through the use of shared decision-making. Methods: We established an interdisciplinary Quality Improvement team composed of nurses, respiratory therapists, and physicians (MDs). The definition of UE was standardized. UE was audited using an apparent cause analysis form to discern associated causes and pinpoint areas for improvement. Interventions were implemented in a step-by-step fashion and reviewed monthly using the model for improvement. A shared decision-making approach fostered collaborative problem-solving. Results: Our baseline UE rate was 2.3 per 100 ventilator days. Retaping, general bedside care, and position change accounted for over 50% of the UE events in 2022. The rate of UE was reduced by 48% by the end of December 2022. We achieved special-cause variation by the end of March 2023. Conclusions: The sole education of medical and nursing providers about various approaches to decreasing unnecessary retaping was ineffective in reducing UE rates. Shared decision-making incorporating inputs from nurses, respiratory therapists, and MDs led to a substantial reduction in the UE rate and underscores the potential of systematic evaluation of risk factors combined with collaborative best practices.

Structure of a human monoclonal antibody in complex with Outer surface protein C (OspC) of the Lyme disease spirochete, Borreliella burgdorferi.

Lyme disease is a tick-borne, multisystem infection caused by the spirochete, Borreliella burgdorferi . Although antibodies have been implicated in the resolution of Lyme disease, the specific B cell epitopes targeted during human infections remain largely unknown. In this study, we characterized and defined the structural epitope of a patient-derived bactericidal monoclonal IgG ("B11") against Outer surface protein C (OspC), a homodimeric lipoprotein necessary for B. burgdorferi tick-mediated transmission and early-stage colonization of vertebrate hosts. High-resolution epitope mapping was accomplished through hydrogen deuterium exchange-mass spectrometry (HDX-MS) and X-ray crystallography. Structural analysis of B11 Fab-OspC A complexes revealed the B11 Fabs associated in a 1:1 stoichiometry with the lateral faces of OspC A homodimers such that the antibodies are essentially positioned perpendicular to the spirochete's outer surface. B11's primary contacts reside within the membrane proximal regions of α-helices 1 and 6 and adjacent loops 5 and 6 in one OspC A monomer. In addition, B11 spans the OspC A dimer interface, engaging opposing α-helix 1', α-helix 2', and loop 2-3' in the second OspC A monomer. The B11-OspC A structure is reminiscent of the recently solved mouse transmission blocking monoclonal IgG B5 in complex with OspC A , indicating a mode of engagement with OspC that is conserved across species. In conclusion, we provide the first detailed insight into the interaction between a functional human antibody and an immunodominant Lyme disease antigen long considered an important vaccine target.

Factors associated with correction of personal protective equipment nonadherence in a multidisciplinary emergency department setting: A retrospective video review.

BACKGROUND: Despite local and national recommendations, health care provider adherence to personal protective equipment (PPE) varied during the COVID-19 pandemic. Previous studies have identified factors influencing initial PPE adherence but did not address factors influencing behaviors leading to correction after initial nonadherence. METHODS: We conducted a retrospective video review of 18 pediatric resuscitations involving aerosol-generating procedures from March 2020 to December 2022 to identify factors associated with nonadherence correction. We quantified adherent and nonadherent providers, instances of PPE nonadherence, and time to correction. We also analyzed correction behaviors, including provider actions and correction locations. RESULTS: Among 434 providers, 362 (83%) were nonadherent with at least 1 PPE. Only 186 of 1,832 instances of nonadherence were corrected, primarily upon room entry and during patient care. Correction time varied by PPE type and nonadherence level (incomplete vs absent). Most corrections were self-initiated, with few reminders from other providers. DISCUSSION: Potential barriers to correction include a lack of social pressure and external reminders. Solutions include optimizing PPE availability, providing real-time feedback, and educating on double gloving. CONCLUSIONS: Most providers were nonadherent to PPE requirements during high-risk infection transmission events. The low correction rate suggests challenges in promoting collective responsibility and maintaining protective behaviors during medical emergencies.

5 strategies for building a top-performing hospital.

A hospital's strategy for attaining high performance under value-based business models should focus on five key objectives: Building meaningful scale and scope; Focusing on more integrated care delivery and management; Attaining demonstrably high levels of clinical quality; Differentiating from the competition through superior customer service; Establishing a competitive cost position.

Effectiveness of a group anger management programme after severe traumatic brain injury.

PRIMARY OBJECTIVE: This study examined the effectiveness of a group approach to the treatment of anger management difficulties for people with severe traumatic brain injury (TBI). RESEARCH DESIGN: Repeated-measures design with convenience sampling. METHOD AND PROCEDURE: Participants were community living clients of a tertiary brain injury service. The group programme consisted of 12 weekly sessions based on a cognitive behavioural therapy (CBT) model, with modifications to incorporate compensations for TBI-related cognitive impairment. Treatment effectiveness was measured using the State-Trait Anger Expression Inventory (STAXI), at pre-treatment, post-treatment and follow-up. MAIN OUTCOMES AND RESULTS: The programme was completed by 52 people across nine groups over the years 1998-2006 and 31 of these attended a follow-up session. Completion of the programme was associated with significant decreases in self-reported frequency with which anger was experienced (STAXI Trait Anger) and frequency of expression of anger (Anger Expression-Out), as well as a significant increase in reported attempts to control feelings of anger (Anger Control); changes were maintained at follow-up assessment. CONCLUSIONS: A group CBT approach shows promise as an effective community-based treatment for anger control issues after severe TBI. Future research directions should include a wait-list control group and objective rating of anger expression.

Nursing satisfaction and Web-based competencies.

This article describes the study of nursing satisfaction with Web-based learning and competency assignment given the learning management system (LMS) change from one LMS to another in 1 year. An anonymous paper-pencil survey was distributed to nursing staff after completing a year with two LMSs and prior to assigning Web-based competency requirements in the newer system (pre) and again after completing requirements (post). Nursing satisfaction and ease of use improved with assignment of requirements. Implications for staff development are described.

Realizing the full financial benefits of true integration.

True health system integration can produce many direct and indirect financial benefits beyond operating cost savings through functional and service centralization or consolidation. These additional benefits of a strong integration strategy include: Improved market position. Expanded continuum of care. Increased scope of services. Improved healthcare quality and organizational performance.

Development of neural perceptual vowel spaces during the first year of life.

This study measured infants' neural responses for spectral changes between all pairs of a set of English vowels. In contrast to previous methods that only allow for the assessment of a few phonetic contrasts, we present a new method that allows us to assess changes in spectral sensitivity across the entire vowel space and create two-dimensional perceptual maps of the infants' vowel development. Infants aged four to eleven months were played long series of concatenated vowels, and the neural response to each vowel change was assessed using the Acoustic Change Complex (ACC) from EEG recordings. The results demonstrated that the youngest infants' responses more closely reflected the acoustic differences between the vowel pairs and reflected higher weight to first-formant variation. Older infants had less acoustically driven responses that seemed a result of selective increases in sensitivity for phonetically similar vowels. The results suggest that phonetic development may involve a perceptual warping for confusable vowels rather than uniform learning, as well as an overall increasing sensitivity to higher-frequency acoustic information.

National, holistic, watershed-scale approach to understand the sources, transport, and fate of agricultural chemicals.

This paper is an introduction to the following series of papers that report on in-depth investigations that have been conducted at five agricultural study areas across the United States in order to gain insights into how environmental processes and agricultural practices interact to determine the transport and fate of agricultural chemicals in the environment. These are the first study areas in an ongoing national study. The study areas were selected, based on the combination of cropping patterns and hydrologic setting, as representative of nationally important agricultural settings to form a basis for extrapolation to unstudied areas. The holistic, watershed-scale study design that involves multiple environmental compartments and that employs both field observations and simulation modeling is presented. This paper introduces the overall study design and presents an overview of the hydrology of the five study areas.

Using heat to characterize streambed water flux variability in four stream reaches.

Estimates of streambed water flux are needed for the interpretation of streambed chemistry and reactions. Continuous temperature and head monitoring in stream reaches within four agricultural watersheds (Leary Weber Ditch, IN; Maple Creek, NE; DR2 Drain, WA; and Merced River, CA) allowed heat to be used as a tracer to study the temporal and spatial variability of fluxes through the streambed. Synoptic methods (seepage meter and differential discharge measurements) were compared with estimates obtained by using heat as a tracer. Water flux was estimated by modeling one-dimensional vertical flow of water and heat using the model VS2DH. Flux was influenced by physical heterogeneity of the stream channel and temporal variability in stream and ground-water levels. During most of the study period (April-December 2004), flux was upward through the streambeds. At the IN, NE, and CA sites, high-stage events resulted in rapid reversal of flow direction inducing short-term surface-water flow into the streambed. During late summer at the IN site, regional ground-water levels dropped, leading to surface-water loss to ground water that resulted in drying of the ditch. Synoptic measurements of flux generally supported the model flux estimates. Water flow through the streambed was roughly an order of magnitude larger in the humid basins (IN and NE) than in the arid basins (WA and CA). Downward flux, in response to sudden high streamflows, and seasonal variability in flux was most pronounced in the humid basins and in high conductivity zones in the streambed.

Comparative study of transport processes of nitrogen, phosphorus, and herbicides to streams in five agricultural basins, USA.

Agricultural chemical transport to surface water and the linkage to other hydrological compartments, principally ground water, was investigated at five watersheds in semiarid to humid climatic settings. Chemical transport was affected by storm water runoff, soil drainage, irrigation, and how streams were linked to shallow ground water systems. Irrigation practices and timing of chemical use greatly affected nutrient and pesticide transport in the semiarid basins. Irrigation with imported water tended to increase ground water and chemical transport, whereas the use of locally pumped irrigation water may eliminate connections between streams and ground water, resulting in lower annual loads. Drainage pathways in humid environments are important because the loads may be transported in tile drains, or through varying combinations of ground water discharge, and overland flow. In most cases, overland flow contributed the greatest loads, but a significant portion of the annual load of nitrate and some pesticide degradates can be transported under base-flow conditions. The highest basin yields for nitrate were measured in a semiarid irrigated system that used imported water and in a stream dominated by tile drainage in a humid environment. Pesticide loads, as a percent of actual use (LAPU), showed the effects of climate and geohydrologic conditions. The LAPU values in the semiarid study basin in Washington were generally low because most of the load was transported in ground water discharge to the stream. When herbicides are applied during the rainy season in a semiarid setting, such as simazine in the California basin, LAPU values are similar to those in the Midwest basins.