Boric acid and Molybdenum trioxide synergistically stimulate osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells.

INTRODUCTION: Metals and their metal ions have been shown to exhibit certain biological functions that make them attractive for use in biomaterials, for example in bone tissue engineering (BTE) applications. Recent data shows that Molybdenum (Mo) is a potent inducer of osteogenic differentiation in human bone marrow-derived mesenchymal stromal cells (BMSCs). On the other hand, while boron (B) has been shown to enhance vascularization in BTE applications, its impact on osteogenic differentiation is volatile: while improved osteogenic differentiation has been described, other data show that B might slow down osteogenic differentiation or reduce the calcification of the extracellular matrix (ECM) when applied in higher doses. Still, the combination of pro-osteogenic Mo and pro-angiogenic B is certainly attractive in the context of biomaterials intended for the use in BTE. METHODS: Therefore, the combined effect of molybdenum trioxide and boric acid at different ratios was investigated in this study to evaluate the effects on the viability, proliferation, osteogenic differentiation, ECM production and maturation of BMSCs. RESULTS: Mo ions proved to be stronger osteoinductive compared to B, in fact, while some osteogenic differentiation markers were downregulated in the presence of B, the presence of Mo provided compensation. The combined application of B and Mo indicated a combination of individual effects, partially even enhancing the expected combined performance of the single stimulations. CONCLUSIONS: The combination of B and Mo might be beneficial for BTE applications since the limited osteogenic properties of B can be compensated by Mo. Furthermore, since B is known to be pro-angiogenic, the combination of both substances may synergistically lead to improved vascularization and bone regeneration. Future studies should assess the angiogenic performance of this combination in greater detail.

Catheter Directed Thrombectomy and Other Deep Venous Interventions in Cancer Patients.

Treating cancer patients with deep venous thrombosis/venous thromboembolism (DVT/VTE) can be challenging as patients are frequently unable to receive the standard therapy of anticoagulation due to the increased risk of bleeding complications seen in this population. Similarly, the hesitation of interventionalists to use thrombolytic agents due to bleeding risks limits percutaneous intervention options as well. Further, outcome data and guidelines do not exist for oncologic patients and often treatment is tailored to patient-specific factors after multidisciplinary discussion. This article reviews specific factors to consider when planning percutaneous treatment of cancer patients with DVT/VTE, focusing on the iliocaval system.

A Primer on Pacemakers and Defibrillators for Nurses.

Although the concepts of pacing have been around for more than half a century, technological advances in cardiac implantable electronic devices (CIEDs) have changed the landscape for patients in need of pacing support or sudden death prevention. Nurses encounter patients with CIEDs in all aspects of the health care setting. Because exciting CIED therapies are on the horizon, nurses must stay up-to-date to promote optimal outcomes for CIED patients. This essential guide provides nurses with a comprehensive overview of the principles of pacing and implantable cardioverter defibrillators (ICDs), as well as innovative technologies such as leadless cardiac pacemakers and subcutaneous ICDs.

[Treatment of unicompartmental osteoarthritis of the knee]. / Therapie der unikompartimentellen Gonarthrose.

Osteoarthritis of the knee is one of the most important degenerative joint diseases in the clinical routine. The treatment of knee osteoarthritis is not only based on the stage, symptoms and duration of the joint disease, but also depends on the existing arthrosis pattern. In the case of unicompartmental arthrosis, damage typical for osteoarthritis is limited to just one joint compartment. Both the conservative and the surgical treatment of unicompartmental osteoarthritis of the knee have to respect the individual characteristics of the respective forms of osteoarthritis. In the context of this manuscript, the genesis, the diagnostics and the guideline-based stage-adapted conservative and operative treatment of unicompartmental osteoarthritis of the knee are addressed.

Development of a hardened THz energy meter for use on the kilojoule-scale, short-pulse OMEGA EP laser.

A highly adaptable and robust terahertz (THz) energy meter is designed and implemented to detect energetic THz pulses from high-intensity (>1018 W/cm2) laser-plasma interactions on the OMEGA EP. THz radiation from the laser driven target is detected by a shielded pyrometer. A second identical pyrometer is used for background subtraction. The detector can be configured to detect THz pulses in the 1 mm to 30 µm (0.3- to 10-THz) range and pulse energies from joules to microjoules via changes in filtration, aperture size, and position. Additional polarization selective filtration can also be used to determine the THz pulse polarization. The design incorporates significant radiation and electromagnetic pulse shielding to survive and operate within the OMEGA EP radiation environment. We describe the design, operational principle, calibration, and testing of the THz energy meter. The pyrometers were calibrated using a benchtop laser and show linear sensitivity to up to 1000 nJ of absorbed energy. The initial results from four OMEGA EP THz experiments detected up to ∼15µJ at the detector, which can correspond to hundreds of mJ depending on THz emission and reflection models.

Predictors for Nonhome Patient Discharge following Lower Extremity Arterial Interventions.

PURPOSE: To identify the variables associated with patient discharge disposition to optimize postprocedural care and discharge planning following lower extremity arterial interventions for peripheral artery disease (PAD). MATERIALS AND METHODS: The 2014-2017 American College of Surgeons National Surgical Quality Improvement Program database was queried using current procedural terminology codes for endovascular infrainguinal interventions for PAD. The main outcome variable of interest was nonhome discharge. Covariates included patient sociodemographic variables, age quartile (upper quartile, ≥77 years), comorbidities (diabetes, renal disease, bleeding disorder, congestive heart failure [CHF], and chronic obstructive pulmonary disease), presence of an open wound before a procedure, type of procedure, operative time, symptom severity, American Society of Anesthesiologists class, and baseline functional status. Univariate analysis and multivariate logistic regression were performed on Stata/SE 15.1. RESULTS: A total of 3,190 patients met the inclusion criteria, of whom 664 (20.8%) had nonhome discharge. Multivariate regression revealed that age (odds ratio [OR], 1.9 for the upper age quartile [>77 years]; 95% confidence interval [CI], 1.46-2.50), operative time (OR, 1.2 per increase in quartile; 95% CI, 1.09-1.30), preoperative wound (OR, 1.5; 95% CI, 1.24-1.90), renal failure (OR, 1.7; 95% CI, 1.30-2.14), CHF (OR, 2.2; 95% CI, 1.51-3.24), symptom severity (OR, 1.7; 95% CI, 1.46-1.98), and independent functional status (OR, 0.74; 95% CI, 0.59-0.92; P = .007) were associated with nonhome discharge. All P values were ≤.001 unless otherwise stated. CONCLUSIONS: Prolonged procedural time, the presence of preprocedural wound and patient comorbidities, symptomatology, and baseline functional status may be used to identify patients who will require a nonhome discharge and early discharge planning.

Understanding umbilical venous catheter insertion practices through a prospective multicenter observational study.

OBJECTIVE: To understand practices of umbilical venous catheter (UVC) insertion in tertiary level neonatal intensive care units (NICU) and investigate the outcomes of subsequent attempts following a failed initial attempt. STUDY DESIGN: Prospective, multi-center observational study of UVC insertions at tertiary level NICUs between March 2019 and January 2020. RESULTS: Of the 101 UVCs inserted at 4 centers, seventy-two (71%) were central at the first attempt and 50% were central at subsequent attempts. Patients with at least 1 failed attempt at insertion were less likely to have a centrally placed UVC (p = .009). Manipulations were less likely to be required when UVC was centrally placed during the first attempt. Maneuvers such as posterior liver mobilization used during insertion were likely to be associated with successful central placement of UVC (p = .0243). The time to complete the procedure was significantly less when the UVC was central at the first attempt (34.2 ± 20.2 vs 46.9 ± 33.8) (p = .0292). Gestational age, birth weight, and age of the baby at the insertion of the UVC, experience of the provider, and type of catheter were comparable among groups. The Shukla formula was most commonly used by providers to measure the depth of UVC placement. CONCLUSION: Repetitive attempts and manipulations were less likely to be beneficial in the successful central placement of UVC in neonates. Additionally, repetitive attempts at insertion prolonged the overall duration of the procedure.

Characteristics of patients presenting to emergency department for primary atrial fibrillation or flutter at an academic medical center.

OBJECTIVE: In the United States, atrial fibrillation (AF) accounts for over 400,000 hospitalizations annually. Emergency Department (ED) physicians have few resources available to guide AF/AFL (atrial flutter) patient triage, and the majority of these patients are subsequently admitted. Our aim is to describe the characteristics and disposition of AF/AFL patients presenting to the University of North Carolina (UNC) ED with the goal of developing a protocol to prevent unnecessary hospitalizations. METHODS: We performed a retrospective electronic medical chart review of AF/AFL patients presenting to the UNC ED over a 15-month period from January 2015 to March 2016. Demographic and ED visit variables were collected. Additionally, patients were designated as either having primary or secondary AF/AFL where primary AF/AFL patients were those in whom AF/AFL was the primary reason for ED presentation. These primary AF/AFL patients were categorized by AF symptom severity score according to the Canadian Cardiovascular Society Severity of Atrial Fibrillation (CCS-SAF) Scale. RESULTS: A total of 935 patients presented to the ED during the study period with 202 (21.5%) having primary AF/AFL. Of the primary AF/AFL patients, 189 (93.6%) had mild-moderate symptom severity (CCS-SAF ≤ 3). The majority of primary AF/AFL patients were hemodynamically stable, with a mean (SD) SBP of 123.8 (21.3), DBP of 76.6 (14.1), and ventricular rate of 93 (21.9). Patients with secondary AF/AFL were older 76 (13.1), p < 0.001 with a longer mean length of stay 6.1 (7.7), p = 0.31. Despite their mild-moderate symptom severity and hemodynamic stability, nearly 2/3 of primary AF/AFL patients were admitted. CONCLUSION: Developing a protocol to triage and discharge hemodynamically stable AF/AFL patients without severe AF/AFL symptoms to a dedicated AF/AFL clinic may help to conserve healthcare resources and potentially deliver more effective care.

Insulin-Dependent Status Influences Post-Procedural Outcomes in Diabetic Patients Following Lower Extremity Endovascular Intervention for Peripheral Arterial Disease.

PURPOSE: Diabetic patients are at increased risk of developing lower extremity peripheral arterial disease (PAD) requiring revascularization. This study assessed the effect of insulin dependence in diabetics on post-procedural outcomes following infra-inguinal endovascular intervention. MATERIALS AND METHODS: The American College of Surgeon's National Surgical Quality Improvement Program database was used to identify 8022 patients undergoing infra-inguinal endovascular interventions between 2014 and 2017. Thirty-day post-procedural outcomes for patients without diabetes, with non-insulin-dependent diabetes mellitus (NIDDM), and with insulin-dependent diabetes mellitus (IDDM) were compared. RESULTS: At presentation, IDDM patients were more likely to present with critical limb ischemia compared to NIDDM and non-diabetic patients. In propensity score-weighted logistic regression analysis, IDDM status was an independent predictor for increased renal complication (odds ratio [OR] = 3.08, confidence interval [CI] = 1.44-6.65), sepsis (OR = 1.68, CI = 1.13-2.48), wound complication (OR = 1.57, CI = 1.09-2.25, p = 0.006), UTI (OR = 2.07, CI = 1.09-3.94, p = 0.03), and readmission (OR = 1.21, CI = 1.03-1.42). NIDDM status was an independent predictor for increased risk of renal complications (OR = 2.80, CI = 1.18-6.63). CONCLUSIONS: IDDM status is an independent predictor for increased risk of 30-day post-procedural complications and readmission compared to both NIDDM and non-diabetic status in patients undergoing lower extremity endovascular interventions for PAD.

STING regulates BCR signaling in normal and malignant B cells.

STING is an endoplasmic reticulum (ER)-resident protein critical for sensing cytoplasmic DNA and promoting the production of type I interferons; however, the role of STING in B cell receptor (BCR) signaling remains unclear. We generated STING V154M knock-in mice and showed that B cells carrying constitutively activated STING specifically degraded membrane-bound IgM, Igα, and Igß via SEL1L/HRD1-mediated ER-associated degradation (ERAD). B cells with activated STING were thus less capable of responding to BCR activation by phosphorylating Igα and Syk than those without activated STING. When immunized with T-independent antigens, STING V154M mice produced significantly fewer antigen-specific plasma cells and antibodies than immunized wild-type (WT) mice. We further generated B cell-specific STINGKO mice and showed that STINGKO B cells indeed responded to activation by transducing stronger BCR signals than their STING-proficient counterparts. When B cell-specific STINGKO mice were T-independently immunized, they produced significantly more antigen-specific plasma cells and antibodies than immunized STINGWT mice. Since both human and mouse IGHV-unmutated malignant chronic lymphocytic leukemia (CLL) cells downregulated the expression of STING, we explored whether STING downregulation could contribute to the well-established robust BCR signaling phenotype in malignant CLL cells. We generated a STING-deficient CLL mouse model and showed that STING-deficient CLL cells were indeed more responsive to BCR activation than their STING-proficient counterparts. These results revealed a novel B cell-intrinsic role of STING in negatively regulating BCR signaling in both normal and malignant B cells.

All-optical intrinsic atomic gradiometer with sub-20 fT/cm/√Hz sensitivity in a 22 µT earth-scale magnetic field.

In this work we demonstrate a high sensitivity atomic gradiometer capable of operation in earth-field level environments. We apply a light-pulse sequence at four times the Larmor frequency to achieve gradiometer sensitivity <20 fT/cm/Hz at the finite field strength of 22 µT. The experimental timing sequence can be tuned to the field magnitude of interest. Our all-optical scalar gradiometer performs a differential measurement between two regions of a single vapor cell on a 4 cm baseline. Our results pave the way for extensions to operation in higher dimensions, vector sensitivity, and more advanced gradiometers.

Development of Tumor-Targeting IRE-1 Inhibitors for B-cell Cancer Therapy.

The IRE-1 kinase/RNase splices the mRNA of the XBP-1 gene, resulting in the spliced XBP-1 (XBP-1s) mRNA that encodes the functional XBP-1s transcription factor that is critically important for the growth and survival of B-cell leukemia, lymphoma, and multiple myeloma (MM). Several inhibitors targeting the expression of XBP-1s have been reported; however, the cytotoxicity exerted by each inhibitor against cancer cells is highly variable. To design better therapeutic strategies for B-cell cancer, we systematically compared the ability of these compounds to inhibit the RNase activity of IRE-1 in vitro and to suppress the expression of XBP-1s in mouse and human MM cell lines. Tricyclic chromenone-based inhibitors B-I09 and D-F07, prodrugs harboring an aldehyde-masking group, emerged as the most reliable inhibitors for potent suppression of XBP-1s expression in MM cells. The cytotoxicity of B-I09 and D-F07 against MM as well as chronic lymphocytic leukemia and mantle cell lymphoma could be further enhanced by combination with inhibitors of the PI3K/AKT pathway. Because chemical modifications of the salicylaldehyde hydroxy group could be used to tune 1,3-dioxane prodrug stability, we installed reactive oxygen species-sensitive structural cage groups onto these inhibitors to achieve stimuli-responsive activities and improve tumor-targeting efficiency.