Assessing the agreement of chronic lung disease of prematurity diagnosis between radiologists and clinical criteria.

BACKGROUND: Chronic lung disease of prematurity (CLD) is the most prevalent complication of preterm birth and indicates an increased likelihood of long-term pulmonary complications. The accurate diagnosis of this condition is critical for long-term health management. Numerous definitions define CLD with different clinical parameters and radiology findings, making diagnosis of the disease ambiguous and potentially inaccurate. METHODS: 95 patients were identified for this study, as determined by the diagnosis or confirmation of CLD in the impression of the radiologist's report on chest x-ray. Pulmonary function and complications were recorded at multiple benchmark timeframes within each patient's first few months of life and used for determining eligibility under each definition. RESULTS: Each clinical definition of CLD had a high sensitivity for patients identified to have CLD by radiologists, correctly fitting over 90% of patients. Most patients included required invasive mechanical ventilation or positive pressure ventilation at 36 weeks postmenstrual age, indicating patients with radiographically confirmed CLD tended to have more severe disease. Radiologists tended to diagnose CLD before 36 weeks postmenstrual age, a timepoint used by multiple standard clinical definitions, with cases called earlier fitting under a larger percentage of definitions than those called later. CONCLUSIONS: Radiologists tend to diagnose CLD in young patients with severe respiratory compromise, and can accurately diagnose the condition before developmental milestones for clinical definitions are met.

Morphological and electrophysiological characterization of a novel displaced astrocyte in the mouse retina.

Astrocytes throughout the central nervous system are heterogeneous in both structure and function. This diversity leads to tissue-specific specialization where morphology is adapted to the surrounding neuronal circuitry, as seen in Bergman glia of the cerebellum and Müller glia of the retina. Because morphology can be a differentiating factor for cellular classification, we recently developed a mouse where glial-fibrillary acidic protein (GFAP)-expressing cells stochastically label for full membranous morphology. Here we utilize this tool to investigate whether morphological and electrophysiological features separate types of mouse retinal astrocytes. In this work, we report on a novel glial population found in the inner plexiform layer and ganglion cell layer which expresses the canonical astrocyte markers GFAP, S100ß, connexin-43, Sox2 and Sox9. Apart from their retinal layer localization, these cells are unique in their radial distribution. They are notably absent from the mid-retina but are heavily concentrated near the optic nerve head, and to a lesser degree the peripheral retina. Additionally, their morphology is distinct from both nerve fiber layer astrocytes and Müller glia, appearing more similar to amacrine cells. Despite this structural similarity, these cells lack protein expression of common neuronal markers. Additionally, they do not exhibit action potentials, but rather resemble astrocytes and Müller glia in their small amplitude, graded depolarization to both light onset and offset. Their structure, protein expression, physiology, and intercellular connections suggest that these cells are astrocytic, displaced from their counterparts in the nerve fiber layer. As such, we refer to these cells as displaced retinal astrocytes.

The process and outcomes of chronic low back pain treatment provided by osteopathic and allopathic physicians: a retrospective cohort study.

CONTEXT: Osteopathic physicians are trained to treat patients with musculoskeletal symptoms, to treat somatic dysfunction with osteopathic manipulative treatment (OMT), and to avoid unnecessarily prescribing drugs such as opioids. It is also generally believed that osteopathic physicians provide a unique patient-centered approach to medical care that involves effective communication and empathy. Such training and characteristics of osteopathic medical care (OMC) may enhance clinical outcomes among patients with chronic pain. OBJECTIVES: The objectives of this study were to measure and compare the process and longitudinal outcomes of chronic low back pain (CLBP) treatment provided by osteopathic and allopathic physicians and to identify mediators of the treatment effects of OMC. METHODS: This retrospective cohort study was conducted utilizing adult participants with CLBP within the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION) from April 2016 through December 2022. Participants having an osteopathic or allopathic physician for at least 1 month prior to registry enrollment were included and followed at quarterly intervals for up to 12 months. Physician communication and physician empathy were measured at registry enrollment. Opioid prescribing and effectiveness and safety outcomes were measured at registry enrollment and for up to 12 months and were analyzed with generalized estimating equations to compare participants treated by osteopathic vs. allopathic physicians. Multiple mediator models, including physician communication, physician empathy, opioid prescribing, and OMT, with covariate adjustments, were utilized to identify mediators of OMC treatment effects. RESULTS: A total of 1,079 participants and 4,779 registry encounters were studied. The mean (SD) age of participants at enrollment was 52.9 (13.2) years, 796 (73.8 %) were female, and 167 (15.5 %) reported having an osteopathic physician. The mean physician communication score for osteopathic physicians was 71.2 (95 % CI, 67.6-74.7) vs. 66.2 (95 % CI, 64.8-67.7) for allopathic physicians (p=0.01). The respective mean scores for physician empathy were 41.6 (95 % CI, 39.9-43.2) vs. 38.3 (95 % CI, 37.6-39.1) (p<0.001). There was no significant difference in opioid prescribing for low back pain between osteopathic and allopathic physicians. Although participants treated by osteopathic physicians reported less severe nausea and vomiting as adverse events potentially attributable to opioids in a multivariable model, neither result was clinically relevant. OMC was associated with statistically significant and clinically relevant outcomes pertaining to low back pain intensity, physical function, and health-related quality of life (HRQOL) over 12 months. Physician empathy was a significant mediator of OMC treatment effects in each of the three outcome domains; however, physician communication, opioid prescribing, and OMT were not mediators. CONCLUSIONS: The study findings indicate that osteopathic physicians provide a patient-centered approach to CLBP treatment, particularly involving empathy, that yields significant and clinically relevant outcomes pertaining to low back pain intensity, physical function, and HRQOL over 12 months of follow-up.

A canine thromboembolic model of anterior circulation large vessel occlusion stroke.

Purpose: To develop a large animal preclinical model of thromboembolic stroke with stable, protracted large vessel occlusion (LVO) utilizing an autologous clot. Materials and methods: A reproducible canine model of large vessel occlusion stroke was established by endovascular placement of an autologous clot into the middle cerebral artery (MCA) of six adult hounds and confirmed using digital subtraction angiography (DSA). Infarct volume and evidence of hemorrhage were determined by magnetic resonance imaging (MRI) 7 h after occlusion and Thrombolysis in Cerebral Infarction scale (TICI) was assessed before and after clot placement and at 1, 6, 7, and 9 h after middle cerebral artery occlusion (MCAO). Heart rate (HR) and blood pressure (BP) were monitored continuously and invasively through an arterial sheath throughout the procedures and complete blood count and blood gas analysis completed at time of sacrifice. Histopathological findings at time of sacrifice were used to confirm stroke volume and hemorrhage. Results: MCAO with resulting TICI 0 flow was observed in all six animals, verified by serial DSA, and lack of collateral flow persisted for 9 h after clot placement until time of sacrifice. The mean infarct volume was 47.0 ± 6.7% of the ipsilateral hemisphere and no events of spontaneous recanalization or clot autolysis were observed. Conclusion: We demonstrate a thromboembolic canine model of MCAO that is both feasible and results in consistent infarct volumes to generate a clinically relevant LVO. This model is important to evaluate treatment of LVO in acute ischemic stroke (AIS) outside the established 4.5 h recombinant tissue plasminogen activator (rTPA) therapeutic window utilizing a prolonged occlusive thrombus.

Magnetic Resonance Elastography (MRE) of Bleomycin-Induced Pulmonary Fibrosis in an Animal Model.

BACKGROUND: Idiopathic pulmonary fibrosis is responsible for 40,000 deaths annually in the United States. A hallmark of idiopathic pulmonary fibrosis is elevated collagen deposition, which alters lung stiffness. Clinically relevant ways to measure changes in lung stiffness during pulmonary fibrosis are not available, and new noninvasive imaging methods are needed to measure changes in lung mechanical properties. OBJECTIVES: Magnetic resonance elastography (MRE) is an in vivo magnetic resonance imaging technique proven to detect changes in shear stiffness in different organs. This study used MRE, histology, and bronchoalveolar lavage (BAL) to study changes in the mechanical and structural properties of the lungs after bleomycin-induced pulmonary fibrosis in pigs. MATERIALS AND METHODS: Pulmonary fibrosis was induced in 9 Yorkshire pigs by intratracheal instillation of 2 doses of bleomycin into the right lung only. Magnetic resonance elastography scans were performed at baseline and week 4 and week 8 postsurgery in a 1.5 T magnetic resonance imaging scanner using a spin-echo echo planar imaging sequence to measure changes in lung shear stiffness. At the time of each scan, a BAL was performed. After the final scan, whole lung tissue was removed and analyzed for histological changes. RESULTS: Mean MRE-derived stiffness measurements at baseline, week 4, and week 8 for the control (left) lungs were 1.02 ± 0.27 kPa, 0.86 ± 0.29 kPa, and 0.68 ± 0.20 kPa, respectively. The ratio of the shear stiffness in the injured (right) lung to the uninjured control (left) lung at baseline, week 4, and week 8 was 0.98 ± 0.23, 1.52 ± 0.41, and 1.64 ± 0.40, respectively. High-dose animals showed increased protein in BAL fluid, elevated inflammation observed by the presence of patchy filtrates, and enhanced collagen and α-smooth muscle actin staining on histological sections. Low-dose animals and the control (left) lungs of high-dose animals did not show significant histopathological changes. CONCLUSION: This study demonstrated that MRE can be used to detect changes in lung stiffness in pigs after bleomycin challenge.

Palliative Medicine Referral and End-of-Life Interventions Among Racial and Ethnic Minority Patients With Advanced or Recurrent Gynecologic Cancer.

BACKGROUND: Referral to palliative medicine (PM) has been shown to improve quality of life, reduce hospitalizations, and improve survival. Limited data exist about PM utilization among racial minorities with gynecologic malignancies. Our objective was to assess differences in palliative medicine referrals and end of life interventions (within the last 30 days of life) by race and ethnicity in a diverse population of gynecologic oncology patients. METHODS: A retrospective cohort study of patients receiving gynecologic oncologic care at a tertiary referral center between 2017 - 2019 was conducted. Patients had either metastatic disease at the time of diagnosis or recurrence. Demographic and clinical data were abstracted. Exploratory analyses were done using chi-square and rank sum tests. Tests were two-sided with significance set at P < .05. RESULTS: A total of 186 patients were included. Of those, 82 (44.1%) were referred to palliative medicine. Underrepresented minorities accounted for 47.3% of patients. English was identified as the primary language for 69.9% of the patients and Spanish in 24.2%. Over 90% of patients had insurance coverage. Ovarian cancer (37.6%) and uterine cancer (32.8%) were the most common sites of origin. Most patients (75%) had advanced stage at the time of diagnosis. Race and language spoken were not associated with referral to PM. Black patients were more likely to have been prescribed appetite stimulants compared to White patients (41% vs 24%, P = .038). Black patients also had a higher number of emergency department visits compared to White patients during the study timeframe. Chemotherapy in the last 30 days of life was also more likely to be given to Black patients compared to White (P = .019). CONCLUSIONS: Race was associated with variation in interventions and healthcare utilization near end-of-life. Understanding the etiologies of these differences is crucial to inform interventions for care optimization as it relates specifically to the health of minority patients.

Detection and Spatiotemporal Analysis of In-vitro 3D Migratory Triple-Negative Breast Cancer Cells.

The invasion of cancer cells into the surrounding tissues is one of the hallmarks of cancer. However, a precise quantitative understanding of the spatiotemporal patterns of cancer cell migration and invasion still remains elusive. A promising approach to investigate these patterns are 3D cell cultures, which provide more realistic models of cancer growth compared to conventional 2D monolayers. Quantifying the spatial distribution of cells in these 3D cultures yields great promise for understanding the spatiotemporal progression of cancer. In the present study, we present an image processing and segmentation pipeline for the detection of 3D GFP-fluorescent triple-negative breast cancer cell nuclei, and we perform quantitative analysis of the formed spatial patterns and their temporal evolution. The performance of the proposed pipeline was evaluated using experimental 3D cell culture data, and was found to be comparable to manual segmentation, outperforming four alternative automated methods. The spatiotemporal statistical analysis of the detected distributions of nuclei revealed transient, non-random spatial distributions that consisted of clustered patterns across a wide range of neighbourhood distances, as well as dispersion for larger distances. Overall, the implementation of the proposed framework revealed the spatial organization of cellular nuclei with improved accuracy, providing insights into the 3 dimensional inter-cellular organization and its progression through time.

Quantifying the Morphology and Mechanisms of Cancer Progression in 3D In-Vitro Environments: Integrating Experiments and Multiscale Models.

Mathematical models of cancer growth have become increasingly more accurate both in the space and time domains. However, the limited amount of data typically available has resulted in a larger number of qualitative rather than quantitative studies. In the present study, we provide an integrated experimental-computational framework for the quantification of the morphological characteristics and the mechanistic modelling of cancer progression in 3D environments. The proposed framework allows for the calibration of multiscale, spatiotemporal models of cancer growth using state-of-the-art 3D cell culture data, and their validation based on the resulting experimental morphological patterns using spatial point-pattern analysis techniques. We applied this framework to the study of the development of Triple Negative Breast Cancer cells cultured in Matrigel scaffolds, and validated the hypothesis of chemotactic migration using a multiscale, hybrid Keller-Segel model. The results revealed transient, non-random spatial distributions of cancer cells that consist of clustered, and dispersion patterns. The proposed model was able to describe the general characteristics of the experimental observations and suggests that chemotactic migration together with random motion was found to be a plausible mechanism leading to accumulation, during the examined time period of development. The developed framework enabled us to pursue two goals; first, the quantitative description of the morphology of cancer growth in 3D cultures using point-pattern analysis, and second, the relation of tumour morphology with underlying biophysical mechanisms that govern cancer growth and migration.

Quality of life and frailty outcomes following surgical and transcatheter aortic valve replacement.

BACKGROUND: Our objective was to report on the prospective outcomes in the areas of depression, quality of life, angina, and frailty in SAVR and TAVR patients with aortic stenosis undergoing aortic valve intervention. METHODS: We recruited 300 patients across 3 groups (TAVR, SAVR, and CABG) over 12 months. Depression, quality of life, frailty, and angina were assessed followed by propensity score matching. RESULTS: Using logistical regression when all patient factors considered for all patients who had SAVR and TAVR, the only preoperative factors that impacted on 1 year mortality was hypertension and STS score. Quality of life improvements within each group over 12 months was significant (p value = 0.0001). Depression at 12 months between groups (p value = 0.0395) and within each group was significant (p value = 0.0073 for SAVR and 0.0001 for TAVR). Angina was most frequent in TAVR at 12 months in the QL (p = 0.0001), PL (p = 0.0007), and improvement was significant in the QL (SAVR p = 0.0010, TAVR p = 0.0001) and PL (SAVR p = 0.0002), TAVR p = 0.0007) domains in both groups. Frailty at 12 months improved in both groups, but was greatest in TAVR (p value = 0.00126). CONCLUSIONS: This 12 months follow up of cardiac surgical patients has revealed significant improvement in PROMs and frailty in all groups by 3 months postoperative regardless of surgical or transcatheter approach. Outcome measures of quality of life and frailty could be utilized as a measure of outcome more regularly in patients undergoing aortic valve surgery regardless of approach.

Continual cerebrospinal fluid sampling in the neonatal domestic piglet for biomarker and discovery studies.

BACKGROUND: Longitudinal access to cerebrospinal fluid (CSF) is useful for biomarker discovery in neurological disorders or diseases affecting CSF composition. Here, we aim to test a new method for insertion of a permanent intrathecal catheter, facilitating longitudinal collection of CSF. NEW METHOD: We surgically placed a permanent intrathecal catheter into the cisterna magna of anesthetized neonatal piglets. The thecal sac was accessed at the L5-S1 spinal level and a radiopaque catheter was inserted under fluoroscopic x-ray guidance to position the tip at the cisterna magna. A titanium access port was connected to the catheter and anchored subcutaneously. Immediately after surgery, we confirmed CSF flow through the catheter and port via needle aspiration. Catheter patency over a two-month study period was determined through periodic CSF collection from the port. RESULTS: Frequent (up to 3 times weekly), longitudinal sampling of CSF was achievable in neonatal piglets up to 60 days after implantation. CSF was readily accessible through the port without major adverse events. Catheterized piglets demonstrated slower, but normal, weight gain compared to control piglets. Post-operative complications were managed with standard access precautions and medications. There were no complications involving the implanted hardware. COMPARISON WITH EXISTING METHOD(S): This method fills a critical gap in the existing methods for longitudinal CSF sampling through an implanted intrathecal catheter system in neonatal piglets. CONCLUSIONS: This novel method is both safe and effective for longitudinal CSF access in the domestic piglet. Catheter patency and access to CSF is maintained over multiple months without major adverse events.

Preferences for Digital Smartphone Mental Health Apps Among Adolescents: Qualitative Interview Study.

BACKGROUND: Mental health digital apps hold promise for providing scalable solutions to individual self-care, education, and illness prevention. However, a problem with these apps is that they lack engaging user interfaces and experiences and thus potentially result in high attrition. Although guidelines for new digital interventions for adults have begun to examine engagement, there is a paucity of evidence on how to best address digital interventions for adolescents. As adolescence is a period of transition, during which the onset of many potentially lifelong mental health conditions frequently occurs, understanding how best to engage this population is crucial. OBJECTIVE: The study aims to detect potential barriers to engagement and to gather feedback on the current elements of app design regarding user experience, user interface, and content. METHODS: This study used a qualitative design. A sample of 14 adolescents was asked to use the app for 1 week and was interviewed using a semistructured interview schedule. The interviews were transcribed and analyzed using thematic analysis. RESULTS: Overall, 13 participants completed the interviews. The authors developed 6 main themes and 20 subthemes based on the data that influenced engagement with and the perceived usefulness of the app. Our main themes were timing, stigma, perception, congruity, usefulness, and user experience. CONCLUSIONS: In line with previous research, we suggest how these aspects of app development should be considered for future apps that aim to prevent and manage mental health conditions.

Quantification of Cerebral Perfusion using Laser Speckle Imaging and Infarct Volume using MRI in a Pre-clinical Model of Posterior Circulation Stroke.

BACKGROUND: Basilar artery occlusion (BAO) is a subset of posterior circulation stroke that carries a mortality as high as 90%.  The current clinical standard to diagnose ischemic stroke include computerized tomography (CT), CT angiography and perfusion and magnetic resonance imaging (MRI). Large animal pre-clinical models to accurately reflect the clinical disease as well as methods to assess stroke burden and evaluate treatments are lacking. METHODS: We describe a canine model of large vessel occlusion (LVO) stroke in the posterior circulation, and developed a laser speckle imaging (LSI) protocol to monitor perfusion changes in real time.  We then utilized high b-value DWI (b=1800s/mm2) MRI to increase detection sensitivity. We also evaluated the ability of magnetic resonance angiography (MRA) to assess arterial occlusion and correlate with DSA. Finally, we verified infarct size from apparent diffusion coefficient (ADC) mapping with histology.  Results:  Administration of thromboembolism occluded the basilar artery as tracked by DSA (n=7).   LSI correlated with DSA, demonstrating a reduction in perfusion after stroke onset that persisted throughout the experiment, allowing us to monitor perfusion in real time.  DWI with an optimized b-value for dogs illustrated the stroke volume and allowed us to derive ADC and magnetic resonance angiography (MRA) images. The MRA performed at the end of the experiment correlated with DSA performed after occlusion. Finally, stroke burden on MRI correlated with histology. CONCLUSIONS: Our studies demonstrate real time perfusion imaging using LSI of a canine thromboembolic LVO model of posterior circulation stroke, which utilizes multimodal imaging important in the diagnosis and treatment of ischemic stroke.

In Vivo Aortic Magnetic Resonance Elastography in Abdominal Aortic Aneurysm: A Validation in an Animal Model.

OBJECTIVES: Using maximum diameter of an abdominal aortic aneurysm (AAA) alone for management can lead to delayed interventions or unnecessary urgent repairs. Abdominal aortic aneurysm stiffness plays an important role in its expansion and rupture. In vivo aortic magnetic resonance elastography (MRE) was developed to spatially measure AAA stiffness in previous pilot studies and has not been thoroughly validated and evaluated for its potential clinical value. This study aims to evaluate noninvasive in vivo aortic MRE-derived stiffness in an AAA porcine model and investigate the relationships between MRE-derived AAA stiffness and (1) histopathology, (2) uniaxial tensile test, and (3) burst testing for assessing MRE's potential in evaluating AAA rupture risk. MATERIALS AND METHODS: Abdominal aortic aneurysm was induced in 31 Yorkshire pigs (n = 226 stiffness measurements). Animals were randomly divided into 3 cohorts: 2-week, 4-week, and 4-week-burst. Aortic MRE was sequentially performed. Histopathologic analyses were performed to quantify elastin, collagen, and mineral densities. Uniaxial tensile test and burst testing were conducted to measure peak stress and burst pressure for assessing the ultimate wall strength. RESULTS: Magnetic resonance elastography-derived AAA stiffness was significantly higher than the normal aorta. Significant reduction in elastin and collagen densities as well as increased mineralization was observed in AAAs. Uniaxial tensile test and burst testing revealed reduced ultimate wall strength. Magnetic resonance elastography-derived aortic stiffness correlated to elastin density (ρ = -0.68; P < 0.0001; n = 60) and mineralization (ρ = 0.59; P < 0.0001; n = 60). Inverse correlations were observed between aortic stiffness and peak stress (ρ = -0.32; P = 0.0495; n = 38) as well as burst pressure (ρ = -0.55; P = 0.0116; n = 20). CONCLUSIONS: Noninvasive in vivo aortic MRE successfully detected aortic wall stiffening, confirming the extracellular matrix remodeling observed in the histopathologic analyses. These mural changes diminished wall strength. Inverse correlation between MRE-derived aortic stiffness and aortic wall strength suggests that MRE-derived stiffness can be a potential biomarker for clinically assessing AAA wall status and rupture potential.

Evaluation of a novel esophageal retractor utilizing vacuum suction and mechanical force for deviating the esophagus.

BACKGROUND: Deviation of the esophagus prevents esophageal injury during atrial fibrillation ablation. OBJECTIVES: This study is to evaluate, in animals, safety and effectiveness of a novel esophageal retractor that utilizes vacuum suction and mechanical force to deviate the esophagus. METHODS: Following general anesthesia, a radiopaque ruler was placed behind the animal perpendicular to the esophagus. The esophageal retractor was inserted and esophagram was completed. Suction force (280-300 mm Hg) was applied to the distal aspect of the device that resulted in adherence of the esophagus in a circumferential manner. Then movement of a deflecting arm was used to deviate the esophagus. Four animal studies completed: (a) deviation distance and presence of trailing edge; (b) effect of 1 hour continuous suction and deviation upon esophageal cellular architecture; (c) impact on luminal esophageal temperature (LET) during high power ablation; and (d) compatibility of esophageal retractor with electroanatomic mapping system. RESULTS: The distance of deviation to the right (26.6 ± 2.5 mm) was higher than to the left (18.7 ± 2.3 mm; P < .01). There was no esophageal trailing edge in 65/68 deviations (96%). With continuous suction for 1 hour, pathology revealed small, <1mm, circular area of hyperemia in the esophageal mucosa. During high power ablation, the maximum increase in LET was 0.2°C. Finally, there was no interference between the device and electro-anatomical mapping system. CONCLUSION: In animal models, the esophageal retractor utilizing vacuum suction was successful at deviating the esophagus without significant trailing edge and with minor (1 mm) injury with prolonged continuous suction.

Ferutinin directs dental pulp-derived stem cells towards the osteogenic lineage by epigenetically regulating canonical Wnt signaling.

Osteoporosis is a silent systemic disease that causes bone deterioration, and affects over 10 million people in the US alone. This study was undertaken to develop a potential stem cell therapy for osteoporosis. We have isolated and expanded human dental pulp-derived stem cells (DPSCs), characterized them, and confirmed their multipotential differentiation abilities. Stem cells often remain quiescent and require activation to differentiate and function. Herein, we show that ferutinin activates DPSCs by modulating the Wnt/ß-catenin signaling pathway and key osteoblast-secreted proteins osteocalcin and collagen 1A1 both mRNA and protein levels. To confirm that ferutinin modulates the Wnt pathway, we inhibited glycogen synthase kinase 3 (GSK3) and found that protein expression patterns were similar to those found in ferutinin-treated DPSCs. To evaluate the role of ferutinin in epigenetic regulation of canonical Wnt signaling, the pathway molecules Wnt3a and Dvl3 were analyzed using chromatin immunoprecipitation (ChIP)-quantitative PCR approaches. We confirmed that active marks of both H3K9 acetylation and H3K4 trimethylation were significantly enhanced in the promoter sites of the WNT3A and DVL3 genes in DPSCs after addition of ferutinin. These data provide evidence that ferutinin activates and promotes osteogenic differentiation of DPSCs, and could be used as an inducer as a potentially effective stem cell therapy for osteoporosis.

Draft Genome Sequence of Multidrug-Resistant Vibrio parahaemolyticus Strain PH698, Infecting Penaeid Shrimp in the Philippines.

The emergence of multidrug-resistant bacterial strains in diverse settings has been reported globally. In the Philippine shrimp aquaculture industry, antibiotics are used for the treatment of bacterial diseases during the production cycle. We report the draft genome of Vibrio parahaemolyticus PH698, a multidrug-resistant strain isolated from a Philippine shrimp farm.

Myeloid Krüppel-Like Factor 2 Critically Regulates K/BxN Serum-Induced Arthritis.

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease, and Krüppel-like factor 2 (KLF2) regulates immune cell activation and function. Herein, we show that in our experiments 50% global deficiency of KLF2 significantly elevated arthritic inflammation and pathogenesis, osteoclastic differentiation, matrix metalloproteinases (MMPs), and inflammatory cytokines in K/BxN serum-induced mice. The severities of RA pathogenesis, as well as the causative and resultant cellular and molecular factors, were further confirmed in monocyte-specific KLF2 deficient mice. In addition, induction of RA resulted in a decreased level of KLF2 in monocytes isolated from both mice and humans along with higher migration of activated monocytes to the RA sites in humans. Mechanistically, overexpression of KLF2 decreased the level of MMP9; conversely, knockdown of KLF2 increased MMP9 in monocytes along with enrichment of active histone marks and histone acetyltransferases on the MMP9 promoter region. These findings define the critical regulatory role of myeloid KLF2 in RA pathogenesis.

The Effect of Microbial Endophyte Consortia on Pseudotsuga menziesii and Thuja plicata Survival, Growth, and Physiology Across Edaphic Gradients.

Increased frequency of droughts and degraded edaphic conditions decreases the success of many reforestation efforts in the Pacific Northwest. Microbial endophyte consortia have been demonstrated to contribute to plant growth promotion and protection from abiotic and biotic stresses - specifically drought conditions - across a number of food crops but for limited tree species. Our research aimed to investigate the potential to improve establishment of economically and ecologically important conifers through a series of in situ field trials and ex situ simulations. Microbial endophyte consortia from Salicaceae, previously shown to confer drought tolerance, and conifer endophyte strains with potentially symbiotic traits were selected for trials with Douglas-fir (Pseudotsuga menziesii) and western redcedar (Thuja plicata). Reductive experimentation was used to subject seedlings to a spectrum of simulated drought levels or presence/absence of fertilizer, testing hypotheses that endophyte consortia impart improved drought resistance and growth promotion, respectively. Inoculation from Salicaceae consortia significantly (p ≤ 0.05) improved survival among seedlings of both species subject to increasing drought stress, with T. plicata seedlings surviving at twofold higher rates in extreme drought conditions. Both species demonstrated improved growth 540 days after inoculation of seed with conifer derived consortia. In the carefully controlled greenhouse experiments with both species, seedling Fv/Fm and SPAD values remained significantly (p ≤ 0.05) more stable in inoculated treatment groups as stress increased. Our findings confirm that multi-strain consortia may be applied as seed or field amendment to conifers, and the approach is efficient in garnering a positive growth response and can mitigate abiotic stressors.

Nanofiber-expanded human CD34+ cells heal cutaneous wounds in streptozotocin-induced diabetic mice.

Despite advances in diabetic wound care, the significant number of amputations that occur every year demands more effective therapeutics. Herein, we offer an aminated polyethersulfone nanofiber-expanded human umbilical cord blood-derived CD34+ cells (henceforth CD34+ cells) effective therapy, tested in cutaneous wounds developed in streptozotocin-induced diabetic NOD/SCID mice. We show that systemic administration of CD34+ cells homed to the wound site and significantly accelerated wound closure. Wound closure was associated with improved re-epithelialization and increased neovascularization; and with decreased sustained pro-inflammatory activity of NF-κB and its downstream effector molecules TNF-α, IL-1ß, and IL-6 at the wound bed. This finding was further supported by the observation of a decreased number of myeloperoxidase positive neutrophils, and concomitantly increased levels of IL-10. In addition, improved granulation tissue formation was observed along with higher collagen deposition and myofibroblasts and decreased expressions of MMP-1. Mechanistically, CD34+ cells reduced the level of MMP-1 expression by inhibiting recruitment of NF-κB to the MMP-1 promoter site in dermal fibroblasts. In summary, we provide evidence of a novel nanofiber-expanded CD34+ stem cell therapeutic development for treating diabetic wounds by defining their cellular and molecular mechanisms.