Berberine potentiates liver inflammation and fibrosis in the PI*Z hAAT transgenic murine model.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is an inherited disease, the common variant caused by a Pi*Z mutation in the SERPINA1 gene. Pi*Z AAT increases the risk of pulmonary emphysema and liver disease. Berberine (BBR) is a nature dietary supplement and herbal remedy. Emerging evidence revealed that BBR has remarkable liver-protective properties against various liver diseases. In the present study, we investigated the therapeutic effects and toxicities of BBR in Pi*Z hepatocytes and Pi*Z transgenic mice. METHODS: Huh7.5 and Huh7.5Z (which carries the Pi*Z mutation) cells were treated with different concentrations of BBR for 48 hours. MTT was performed for cell viability assay. Intracellular AAT levels were evaluated by western blot. In vivo studies were carried out in wild type, native phenotype AAT (Pi*M), and Pi*Z AAT transgenic mice. Mice were treated with 50 mg/kg/day of BBR or solvent only by oral administration for 30 days. Western blot and liver histopathological examinations were performed to evaluate therapeutic benefits and liver toxicity of BBR. RESULTS: BBR reduced intracellular AAT levels in Huh7.5Z cells, meanwhile, no Pi*Z-specific toxicity was observed. However, BBR did not reduce liver AAT load but significantly potentiated liver inflammation and fibrosis accompanying the activation of unfolded protein response and mTOR in Pi*Z mice, but not in wild type and Pi*M mice. CONCLUSIONS: BBR exacerbated liver inflammation and fibrosis specifically in Pi*Z mice. This adverse effect may be associated with the activation of unfolded protein response and mTOR. This study implicates that BBR should be avoided by AATD patients.

Current challenges in pulmonary nontuberculous mycobacterial infection: a case series with literature review.

BACKGROUND: The prevalence of nontuberculous mycobacteria pulmonary disease (NTM-PD), particularly caused by Mycobacterium avium complex (MAC), is rising due to improved diagnostics, increased awareness, and more susceptible populations. NTM-PD significantly affects quality of life and imposes substantial economic costs. Understanding its clinical features, risk factors, and treatment challenges is vital for enhancing patient outcomes. PATIENTS AND METHODS: A convenience sample from the University of Connecticut Health Center and Wayne State University involving patients with NTM-PD from 2021 to 2024 was studied retrospectively. Cases were selected to demonstrate typical diagnostic and treatment challenges, followed by a multidisciplinary roundtable discussion to examine patient-centered care strategies. RESULTS: Analysis of six cases pinpointed chronic lung conditions and immunomodulatory therapy as key risk factors. Standard treatment, involving extensive multi-drug regimens, frequently results in poor adherence due to side effects and complex management requirements. The discussions underlined the importance of a customized, interdisciplinary approach to improve treatment effectiveness and patient quality of life. CONCLUSIONS: NTM-PD is an escalating public health issue with notable clinical and economic consequences. Managing this disease effectively demands a comprehensive, patient-centered strategy that includes precise diagnosis, flexible treatment plans, and collaborative care.

This paper focuses on a type of lung disease caused by nontuberculous mycobacteria (NTM), which are bacteria found in the environment. NTM pulmonary disease has become more common due to better diagnostic methods, increased awareness, and a growing number of people with conditions that make them more vulnerable to infections. This disease can seriously affect a person's quality of life and is challenging to treat because it often requires long and complex antibiotic regimens.The authors, who have expertise in pulmonary diseases and infectious diseases, reviewed the medical records of six patients treated for NTM disease at the University of Connecticut Health Center and Wayne State University between 2021 and 2024. Following the submission of case synopses, the authors engaged in a discussion to explore the challenges of managing NTM infections. The discussion focused on identifying the best practices for diagnosis and treatment, emphasizing a patient-centered approach to care.Patients with preexisting lung conditions or those undergoing certain medical treatments are more susceptible to developing NTM lung disease. The treatment often involved multiple drugs, which posed challenges for patients due to side effects and the complexity of the regimen. The findings underscored the importance of a personalized, collaborative approach in treating NTM lung disease to improve patient outcomes and quality of life.

Robot-assisted nephroureterectomy: surgical and mid-term oncological outcomes in over 1100 patients (ROBUUST 2.0 collaborative group).

OBJECTIVE: To analyse surgical, functional, and mid-term oncological outcomes of robot-assisted nephroureterectomy (RANU) in a contemporary large multi-institutional setting. PATIENTS AND METHODS: Data were retrieved from the ROBotic surgery for Upper tract Urothelial cancer STtudy (ROBUUST) 2.0 database, an international, multicentre registry encompassing data of patients with upper urinary tract urothelial carcinoma undergoing curative surgery between 2015 and 2022. The analysis included all consecutive patients undergoing RANU except those with missing data in predictors. Detailed surgical, pathological, and postoperative functional data were recorded and analysed. Oncological time-to-event outcomes were: recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Survival analysis was performed using the Kaplan-Meier method, with a 3-year cut-off. A multivariable Cox proportional hazard model was built to evaluate predictors of each oncological outcome. RESULTS: A total of 1118 patients underwent RANU during the study period. The postoperative complications rate was 14.1%; the positive surgical margin rate was 4.7%. A postoperative median (interquartile range) estimated glomerular filtration rate decrease of -13.1 (-27.5 to 0) mL/min/1.73 m2 from baseline was observed. The 3-year RFS was 59% and the 3-year MFS was 76%, with a 3-year OS and CSS of 76% and 88%, respectively. Significant predictors of worse oncological outcomes were bladder-cuff excision, high-grade tumour, pathological T stage ≥3, and nodal involvement. CONCLUSIONS: The present study contributes to the growing body of evidence supporting the increasing adoption of RANU. The procedure consistently offers low surgical morbidity and can provide favourable mid-term oncological outcomes, mirroring those of open NU, even in non-organ-confined disease.

X-ray Induced Cycling of Rare-Earth Elements between Bulk and Interfacial Liquid.

Reversible cycling of rare-earth elements between an aqueous electrolyte solution and its free surface is achieved by X-ray exposure. This exposure alters the competitive equilibrium between lanthanide ions bound to a chelating ligand, diethylenetriamine pentaacetic acid (DTPA), in the bulk solution and to insoluble monolayers of extractant di-hexadecyl phosphoric acid (DHDP) at its surface. Evidence for the exposure-induced temporal variations in the lanthanide surface density is provided by X-ray fluorescence near total reflection measurements. Comparison of results when X-rays are confined to the aqueous surface region to results when X-rays transmit into the bulk solution suggests the importance of aqueous radiolysis in the adsorption cycle. Amine binding sites in DTPA are identified as a likely target of radiolysis products. The molecules DTPA and DHDP are like those used in the separation of lanthanides from ores and in the reprocessing of nuclear fuel. These results suggest that an external source of X-rays can be used to drive rare-earth element separations. More generally, use of X-rays to controllably dose a liquid interface with lanthanides could trigger a range of interfacial processes, including enhanced metal ion extraction, catalysis, and materials synthesis.

miRNA-mediated control of gephyrin synthesis drives sustained inhibitory synaptic plasticity.

Activity-dependent protein synthesis is crucial for long-lasting forms of synaptic plasticity. However, our understanding of translational mechanisms controlling GABAergic synapses is limited. One distinct form of inhibitory long-term potentiation (iLTP) enhances postsynaptic clusters of GABAARs and the primary inhibitory scaffold, gephyrin, to promote sustained synaptic strengthening. While we previously found that persistent iLTP requires mRNA translation, the mechanisms controlling plasticity-induced gephyrin translation remain unknown. We identify miR153 as a novel regulator of Gphn mRNA translation which controls gephyrin protein levels and synaptic clustering, ultimately impacting inhibitory synaptic structure and function. iLTP induction downregulates miR153, reversing its translational suppression of Gphn mRNA and promoting de novo gephyrin protein synthesis and synaptic clustering during iLTP. Finally, we find that reduced miR153 expression during iLTP is driven by an excitation-transcription coupling pathway involving calcineurin, NFAT and HDACs, which also controls the miRNA-dependent upregulation of GABAARs. Together, we delineate a miRNA-dependent post-transcriptional mechanism that controls the expression of the key synaptic scaffold, gephyrin, and may converge with parallel miRNA pathways to coordinate gene upregulation to maintain inhibitory synaptic plasticity.

Automated Identification of Patients' Unmet Social Needs in Clinical Text Using Natural Language Processing.

Objective: To develop natural language processing (NLP) solutions for identifying patients' unmet social needs to enable timely intervention. Patients and Methods: Design: A retrospective cohort study with review and annotation of clinical notes to identify unmet social needs, followed by using the annotations to develop and evaluate NLP solutions. Participants: A total of 1103 primary care patients seen at a large academic medical center from June 1, 2019, to May 31, 2021 and referred to a community health worker (CHW) program. Clinical notes and portal messages of 200 age and sex-stratified patients were sampled for annotation of unmet social needs. Systems: Two NLP solutions were developed and compared. The first solution employed similarity-based classification on top of sentences represented as semantic embedding vectors. The second solution involved designing of terms and patterns for identifying each domain of unmet social needs in the clinical text. Measures: Precision, recall, and f1-score of the NLP solutions. Results: A total of 5675 clinical notes and 475 portal messages were annotated, with an inter-annotator agreement of 0.938. The best NLP solution achieved an f1-score of 0.95 and was applied to the entire CHW-referred cohort (n=1103), of whom >80% had at least 1 unmet social need within the 6 months before the first CHW referral. Financial strain and health literacy were the top 2 domains of unmet social needs across most of the sex and age strata. Conclusion: Clinical text contains rich information about patients' unmet social needs. The NLP can achieve good performance in identifying those needs for CHW referral and facilitate data-driven research on social determinants of health.

Incidence of Ipsilateral Femoral Neck and Shaft Fractures in Pediatric and Adolescent Patients.

OBJECTIVES: To identify the incidence, patient characteristics, and effectiveness of radiographic screening methods for detecting ipsilateral femoral neck and shaft fractures in pediatric and adolescent trauma patients. DESIGN: Retrospective cohort study. SETTING: This study was conducted at a tertiary pediatric trauma hospital. PATIENT SELECTION CRITERIA: Patients younger than 18 years treated for a femoral shaft fracture between 2004 and 2018 were reviewed. Pathologic (metabolic bone disease or bone lesion), periprosthetic, and penetrating traumatic femoral shaft fractures were excluded. OUTCOME MEASUREMENTS AND COMPARISONS: Patient demographics, mechanisms of injury, treatment methods, and associated injuries were analyzed. Pretreatment x-rays and computed tomography (CT) scans were reviewed for the identification of ipsilateral femoral neck and shaft fractures. RESULTS: Among the 840 pediatric patients included in this study, 4 patients (0.5%) sustained ipsilateral femoral neck and shaft fractures. All the femoral neck fractures were observed in adolescents (aged 13-17 years) and involved in high-energy traumas. In adolescents involved in high-energy trauma, the incidence increased to 1.7%. Pretreatment sensitivity of both x-rays and CT scans was only 50% for the detection of femoral neck fractures. CONCLUSIONS: This study reveals that ipsilateral femoral neck and shaft fractures in pediatric patients are rare, occurring in adolescents involved in high-energy trauma. The findings suggest the need for a selective, rather than routine, use of CT scans based on the patient's age and the mechanism of injury. The use of alternative imaging methods such as magnetic resonance imaging should be considered to balance diagnostic accuracy while minimizing radiation exposure. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Intraoperative guidance of pancreatic cancer resection using a toll like receptor 2 targeted fluorescence molecular imaging agent.

To increase the achievement of negative R0 surgical margins and increase the low survival rates of pancreatic cancer, improvements in assessing tumor margins during surgical resections are needed. This can be accomplished by using pancreatic cancer-targeted fluorescence molecular imaging agents to intraoperatively detect tumor margins in real-time. Since toll like receptor 2 (TLR2) is broadly expressed among many cancer types including pancreatic adenocarcinomas, a high-affinity TLR2-targeted fluorescence molecular imaging agent (TLR2L-800) was developed. We investigate the potential for increased survival by employing real-time intraoperative tumor detection in a preclinical orthotopic human pancreatic xenograft tumor model using TLR2L-800. Three cohorts of nude mice bearing orthotopic human pancreatic xenograft tumors were intravenously injected with TLR2L-800. At 24 h postinjection, one cohort underwent in vivo fluorescence-guided surgical removal of tumors using a real-time fluorescence imaging platform, a second cohort underwent visible light surgery, and a third cohort did not undergo surgery. A fourth, non-tumor-bearing cohort was administered TLR2L-800 with no surgery. At 41 d post-surgery, the survival rates were 53% for the fluorescence-guided surgery group and 0% for both the visible light surgery group and the tumor-bearing no surgery group. The overall 200 d survival rate of 35% for the fluorescence-guided surgery group was significant compared to 0% for the visible light surgery group (p-value=0.0018). This study demonstrates the potential of increasing disease-free survival for patients with pancreatic cancer by increasing the attainment of R0 margins using a novel tumor-targeted lipopeptide ligand-based fluorescence molecular imaging agent, TLR2L-800, during real-time fluorescence-guided surgery.

Short- and Long-Term Outcomes of Thoracoscopic and Open Repair For Esophageal Atresia and Tracheoesophageal Fistula.

BACKGROUND: The aim was to evaluate short- and long-term outcomes for thoracoscopic repair of EA/TEF and compare with open repair. METHODS: Patients who underwent EA/TEF repair during 2000-2020 were evaluated retrospectively. Patients with delayed repair were excluded. Demographic, operative, outcome data was collected. Outcomes were compared using Wilcoxon-rank sum tests for continuous, Chi-squared/Fisher's exact tests for categorical data. RESULTS: There were 104 patients with primary repair, 49 (47.1%) underwent thoracoscopic repair per surgeon's choice. Type C accounted for 101 (97.1%) of the cases. Gestational age and birth weight were higher in the thoracoscopy group (p = 0.001). The rate of ≥3 VACTERL anomalies was higher in the OR group (p = 0.016). Operative time, rate of anastomotic leak, time to first oral feeding were similar (p > 0.05). Thoracoscopy group had decreased length of ventilation (p = 0.026) and length of stay (p = 0.029). The incidence of anastomotic stricture was higher in the thoracoscopy group (p = 0.012). Recurrent TEF was one case in each group. Rates of tube feeding at discharge and in first year were similar (p > 0.05), rate in third year was decreased (p = 0.032) in the thoracoscopy group. Rates of anti-reflux medication in first and third years, and fundoplication rate were similar (p > 0.05). CONCLUSIONS: Many of the short- and long-term outcomes are comparable between thoracoscopic and open repair of EA/TEF. Length of ventilation, length of stay are decreased in the thoracoscopy group. Anastomotic stricture is higher, the need for long-term tube feeding is lower after thoracoscopic repair. Although these results could be affected by selection bias, they are still promising for advancing thoracoscopic repair of EA/TEF safely and efficiently. LEVEL OF EVIDENCE: Level III.

The copepod Acartia spinicauda feeds less and dies more under the influences of solar ultraviolet radiation and elevated pCO2.

While solar ultraviolet radiation (UVR) is known to impact zooplankton, little has been documented on its impacts under elevated pCO2. Here, we show that exposure to UVR decreased the feeding and survival rates of the copepod Acartia spinicauda, that artificial UV-B of 2.25 W·m-2 for 4 h resulted in a 52 % inhibition of its grazing rates and a 45 % reduction in survival rates compared to visible light alone. On the other hand, an increase in pCO2 to 1000 µatm (pH drop of 0.4) immediately and significantly increased the UVR-induced inhibition of feeding. Subsequently, the combination of the high pCO2 (1000 µatm) and UVR resulted in about 65 % lethal impact, with UV-A contributing 21 % and UV-B 44 % compared to the visible light alone and ambient pCO2 conditions. While the copepod was shown to be able to sense and escape from UV-exposed areas, these findings suggest that UVR impacts on the copepod can be exacerbated with progressive ocean acidification or in high CO2 waters, including upwelled regions.

Achieving optical transparency in live animals with absorbing molecules.

Optical imaging plays a central role in biology and medicine but is hindered by light scattering in live tissue. We report the counterintuitive observation that strongly absorbing molecules can achieve optical transparency in live animals. We explored the physics behind this observation and found that when strongly absorbing molecules dissolve in water, they can modify the refractive index of the aqueous medium through the Kramers-Kronig relations to match that of high-index tissue components such as lipids. We have demonstrated that our straightforward approach can reversibly render a live mouse body transparent to allow visualization of a wide range of deep-seated structures and activities. This work suggests that the search for high-performance optical clearing agents should focus on strongly absorbing molecules.

Root cause analysis of cases involving diagnosis.

Diagnostic errors comprise the leading threat to patient safety in healthcare today. Learning how to extract the lessons from cases where diagnosis succeeds or fails is a promising approach to improve diagnostic safety going forward. We present up-to-date and authoritative guidance on how the existing approaches to conducting root cause analyses (RCA's) can be modified to study cases involving diagnosis. There are several diffierences: In cases involving diagnosis, the investigation should begin immediately after the incident, and clinicians involved in the case should be members of the RCA team. The review must include consideration of how the clinical reasoning process went astray (or succeeded), and use a human-factors perspective to consider the system-related contextual factors in the diagnostic process. We present detailed instructions for conducting RCA's of cases involving diagnosis, with advice on how to identify root causes and contributing factors and select appropriate interventions.

Associations Between Integration and Patient Experience in Hospital-Based Health Systems: An Exploration of Horizontal and Vertical Forms of Integration.

GOAL: The U.S. hospital sector is experiencing record levels of integration, with more than half of U.S. physicians and nearly three quarters of all hospitals affiliated with one of slightly more than 630 health systems. However, there is growing evidence to suggest that health system integration is associated with more expensive and lower quality care. The goal of this research is to explore the associations between forms of health system integration and hospital patient experience scores. METHODS: A cross-section of data for the year 2019 was assembled and analyzed from the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) patient experience survey. Data from the Compendium of US Health Systems, published by the Agency for Healthcare Research and Quality (AHRQ), and the American Hospital Association (AHA) Annual Survey were used to obtain independent variables and hospital-level covariates. A series of multivariable regressions was used to explore the associations between forms of health system integration and hospital patient experience scores across three domains: overall impression of the hospital; experiences with staff; and the hospital environment. Forms of both horizontal integration (i.e., number of hospitals owned by hospital-based health systems) and vertical integration (i.e., physician-hospital integration, nursing home ownership, accountable care organization [ACO] participation, group purchasing, contract management, offering insurance products, and investor ownership) were explored. PRINCIPAL FINDINGS: Although horizontal integration was not associated with any meaningful differences in patient experience scores, health systems with physician-hospital integration were associated with overall impression scores that were 2 percentage points higher than systems without physician integration. Similarly, contract management and membership in a group purchasing organization were associated with overall impression and environment scores that were 2 to 3 percentage points higher than hospitals that did not engage in those forms of integration. By contrast, investor ownership was associated with a 5% lower score for overall patient experience compared with other forms of ownership. PRACTICAL APPLICATIONS: The findings of this study suggest that hospitals in more vertically integrated systems may have higher patient experience scores than independent hospitals and those that belong exclusively to horizontally integrated systems. Thus, there are elements of vertical integration that could benefit patients and be worth pursuing. Conversely, higher degrees of horizontal integration in the form of multihospital ownership may not be of any benefit to patients and should be pursued with caution.

Reducing therapeutic inertia in type 2 diabetes.

BACKGROUND: Therapeutic inertia describes a failure to establish appropriate treatment targets and escalate treatment to achieve those targets. This inertia can be measured, and evidence of this inertia is present in approximately one-third of diabetes management consultations. This inertia describes a failure in the system to produce change, rather than assigning fault to the physician or patient. OBJECTIVE: This article discusses the importance of reducing therapeutic inertia in type 2 diabetes and focusing on reducing overall cardiovascular risk. DISCUSSION: This article discusses approaches to reducing treatment inertia in type 2 diabetes (ie identify the problem, get permission, set goals, measure progress and alter treatment to reach those goals). The treat-to-target methodology, the STABLE (Smoking cessation, Target organ involvement, HbA1c, Blood pressure, Lipid profile, Energy balance) acronym and practical approaches are described.

Survey effort and targeted landbird community metrics at Indiana lowland forest restoration sites.

Many sampling and analytical methods can estimate the abundance, distributions, and diversity of birds and other wildlife. However, challenges with sample size and analytical capacity can make these methods difficult to implement for resource-limited monitoring programs. To apprise efficient and attainable sampling designs for landbird monitoring programs with limited observational data, we used breeding season bird point survey data collected in 2016 at four forest restoration sites in Indiana, USA. We evaluated three subsets of observed species richness, total possibly breeding landbirds, Partners in Flight Regional Conservation Concern (PIF RCC) landbirds, and interior forest specialists (IFSs). Simulated surveys based on field data were used to conduct Bayesian Michaelis-Menten curve analyses estimating observed species as a function of sampling effort. On comparing simulated survey sets with multiple habitat types versus those with one habitat, we found that those with multiple habitat types had estimated 39%-83% greater observed PIF RCC species richness and required 41%-55% fewer visits per point to observe an equivalent proportion of PIF RCC species. Even with multiple habitats in a survey set, the number of visits per point required to detect 50% of observable species was 30% higher for PIF RCC species than for total breeding landbird species. Low detection rates of IFS species at two field sites made precise estimation of required effort to observe these species difficult. However, qualitatively, we found that only sites containing mature forest fragments had detections of several bird species designated as high-confidence IFS species. Our results suggest that deriving specialized species diversity metrics from point survey data can add value when interpreting those data. Additionally, designing studies to collect these metrics may require explicitly planning to visit multiple habitat types at a monitoring site and increasing the number of visits per survey point. Integr Environ Assess Manag 2024;00:1-15. © 2024 The Author(s). Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Opportunity and Opportunism in Artificial-Intelligence-Powered Data Extraction: A Value-Centered Approach.

Radiologists' traditional role in the diagnostic process is to respond to specific clinical questions and reduce uncertainty enough to permit treatment decisions. This charge is rapidly evolving due to forces such as artificial intelligence [AI], big data [opportunistic imaging, imaging prognostication], and advanced diagnostic technologies. A new "modernistic" paradigm is emerging whereby radiologists, in conjunction with computer algorithms, will be tasked with extracting as much information from imaging data as possible, often without a specific clinical question being posed and independent of any stated clinical need. In addition, AI algorithms are increasingly able to predict long-term outcomes using data from seemingly normal examinations, enabling AI-assisted prognostication. As these algorithms become a standard component of radiology practice, the sheer amount of information they demand will increase the need for streamlined workflows, communication, and data management techniques. In addition, the provision of such information raises reimbursement, liability, and access issues. Guidelines will be needed to ensure all patients have access to the benefits of this new technology and guarantee mined data do not inadvertently create harm. In this article, we discuss challenges and opportunities relevant to radiologists in this changing landscape, with an emphasis on ensuring that radiologists provide high-value care.

Three-dimensional virtual histology of the rat uterus musculature using micro-computed tomography.

Contractions of the uterus play an important role in menstruation and fertility, and contractile dysfunction can lead to chronic diseases such as endometriosis. However, the structure and function of the uterus are difficult to interrogate in humans, and thus animal studies are often employed to understand its function. In rats, anatomical studies of the uterus have typically been based on histological assessment, have been limited to small segments of the uterine structure, and have been time-consuming to reconstruct at the organ scale. This study used micro-computed tomography imaging to visualise the muscle structures in the entire non-pregnant rat uterus and assess its use for 3D virtual histology. An assessment of the rodent uterus is presented to (i) quantify muscle thickness variations along the horns, (ii) identify predominant fibre orientations of the muscles and (iii) demonstrate how the anatomy of the uterus can be mapped to 3D volumetric meshes via virtual histology. Micro-computed tomography measurements were validated against measurements from histological sections. The average thickness of the myometrium was found to be 0.33 ± 0.11 mm and 0.31 ± 0.09 mm in the left and right horns, respectively. The micro-computed tomography and histology thickness calculations were found to correlate strongly at different locations in the uterus: at the cervix, r = 0.87, and along the horn from the cervical end to the ovarian end, respectively, r = 0.77, r = 0.89 and r = 0.54, with p < 0.001 in every location. This study shows that micro-computed tomography can be used to quantify the musculature in the whole non-pregnant uterus and can be used for 3D virtual histology.

A bioassay that yields quantifiable symptoms of cucurbit yellow vine disease caused by Serratia marcescens.

Cucurbit yellow vine disease (CYVD), which is caused by the gram-negative bacterium Serratia marcescens and transmitted by squash bugs (Anasa tristis DeGeer), is a devastating disease of cucurbit crops that is emerging rapidly in the eastern half of the U.S. The lack of a robust pathogenicity assay for CYVD in the laboratory has hampered functional tests using genomic sequences to investigate the biology of this phytopathogen. In this study we developed and validated a bioassay that yielded consistent and quantifiable CYVD symptoms on squash in the lab. We compared inoculation by wounding with a multipronged floral pin frog to inoculation by injection in which a needle was moved in and out of the stem multiple times in each of multiple piercings to mimic the feeding behavior of squash bugs. We found that inoculation by needle injection of ≥108 CFU/ml of S. marcescens into the stem of squash (Cucurbita pepo) plants at the cotyledon growth stage reproducibly induced CYVD symptoms, whereas injecting 106 or 107 CFU/ml did not. Additionally, we found that S. marcescens induced symptoms on all of the squash cultivars tested, and induced symptoms that have not been previously reported, including stem elongation and leaf cupping. In short, through our injection approach of mimicking the natural process of S. marcescens transmission by squash bug feeding, we obtained robust and quantifiable CYVD symptoms. This laboratory bioassay provides a crucial tool for investigating the biology and pathology of this emerging pathogen and for plant breeding screens aimed at combatting CYVD.

Efficacy of Direct Versus Peripheral Adjuvant Dexamethasone on Duration and Rebound Pain in Regional Anesthesia for Outpatient Distal Radius Fracture Fixation: A Prospective Randomized Controlled Blinded Study.

BACKGROUND: Despite increasingly wider use, there remains controversy among anesthesiologists regarding preferred formulations and the role of steroid adjuvants in regional anesthesia. There is also uncertainty in the role of dexamethasone when administered directly versus peripherally. We hypothesize that directly mixing dexamethasone into the regional nerve block rather than peripherally administered intravenous dexamethasone will demonstrate a difference in efficacy concerning duration and rebound pain, decreased postoperative pain scores, or opioid consumption within the short-term postoperative period. METHODS: A prospective, randomized controlled blinded study was conducted for patients undergoing open reduction and internal fixation with a volar plate technique for distal radius fractures. Patients were randomized for their preoperative anesthesia. One group had ultrasound-guided supraclavicular block with ropivacaine with a direct mix of dexamethasone 4 mg (Direct group), while the other group had ultrasound-guided supraclavicular block with ropivacaine and peripheral intravenous dexamethasone 4 mg (Indirect group). Data was collected pre, intra, and postoperatively. RESULTS: Fifty patients consented and participated in the study, with 27 participants in the direct group and 23 participants in the indirect group. Compared to intravenous administration, directly administered dexamethasone demonstrated a significant difference in the average time for the block to fade, onset of motor and sensory recovery, and block resolution. CONCLUSION: Our findings prove that directly mixing dexamethasone compared to peripherally administered intravenous dexamethasone will demonstrate a difference in efficacy with regards to duration and rebound pain, but do not prove that there will be a difference in decreased postoperative pain scores or opioid consumption within the 24-hour postoperative period. LEVEL OF EVIDENCE: Prognosis Level I.