Showing papers by "Saint Louis University published in 2022"

Hepatic stellate cells in physiology and pathology

Abstract: Hepatic stellate cells (HSCs) comprise a minor cell population in the liver but serve numerous critical functions in the normal liver and in response to injury. HSCs are primarily known for their activation upon liver injury and for producing the collagen-rich extracellular matrix in liver fibrosis. In the absence of liver injury, HSCs reside in a quiescent state, in which their main function appears to be the storage of retinoids or vitamin A-containing metabolites. Less appreciated functions of HSCs include amplifying the hepatic inflammatory response and expressing growth factors that are critical for liver development and both the initiation and termination of liver regeneration. Recent single-cell RNA sequencing studies have corroborated earlier studies indictaing that HSC activation involves a diverse array of phenotypic alterations and identified unique HSC populations. This review serves to highlight these many functions of HSCs, and to briefly describe the recent genetic tools that will help to thoroughly investigate the role of HSCs in hepatic physiology and pathology.

Number Needed to Treat Network Meta-Analysis to Compare Biologic Drugs for Moderate-to-Severe Psoriasis

Abstract: Number needed to treat (NNT) estimates are a practical metric to help identify the most effective therapies. Our objective is to compare 11 biologic drugs for moderate-to-severe psoriasis in terms of NNT. The NNT data were obtained from a Bayesian network meta-analysis of 42 double-blind, randomized, phase 3 clinical trials for 11 biologics (adalimumab, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab). We determined NNT to achieve Psoriasis Area and Severity Index (PASI) 75/90/100 responses at weeks 4, 8, 12, 16, and 48/52 and Dermatology Life Quality Index (DLQI) response 0, 1 at week 12. Highest efficacy (lowest NNT) was with brodalumab and ixekizumab for PASI 90 at weeks 4, 8, and 12; ixekizumab for PASI 90/100 at week 16; and brodalumab for PASI 100 at week 12. After 48/52 weeks, risankizumab had the highest efficacy for PASI 90/100 overlapping with guselkumab, brodalumab, and ixekizumab for PASI 90 and with brodalumab and ixekizumab for PASI 100. Ixekizumab had the highest efficacy for DLQI (0,1) at week 12. Brodalumab and ixekizumab had the lowest NNTs for achieving PASI responses at early time points and were not significantly different than risankizumab and guselkumab after 48/52 weeks.

Role of Bevacizumab on Vascular Endothelial Growth Factor in Apolipoprotein E Deficient Mice after Traumatic Brain Injury

Abstract: Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB). Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI and to be overexpressed in the absence of apolipoprotein E (ApoE). Bevacizumab, a VEGF inhibitor, demonstrated neuroprotective activity in several models of TBI. However, the effects of bevacizumab on Apo-E deficient mice are not well studied. The present study aimed to evaluate VEGF expression and the effects of bevacizumab on BBB and neuroinflammation in ApoE-/- mice undergoing TBI. Furthermore, for the first time, this study evaluates the effects of bevacizumab on the long-term consequences of TBI, such as atherosclerosis. The results showed that motor deficits induced by controlled cortical impact (CCI) were accompanied by increased brain edema and VEGF expression. Treatment with bevacizumab significantly improved motor deficits and significantly decreased VEGF levels, as well as brain edema compared to the control group. Furthermore, the results showed that bevacizumab preserves the integrity of the BBB and reduces the neuroinflammation induced by TBI. Regarding the effects of bevacizumab on atherosclerosis, it was observed for the first time that its ability to modulate VEGF in the acute phase of head injury prevents the acceleration of atherosclerosis. Therefore, the present study demonstrates not only the neuroprotective activity of bevacizumab but also its action on the vascular consequences related to TBI.

First observation of mercury species on an important water vapor channel in the southeastern Tibetan Plateau

Abstract: Abstract. The Tibetan Plateau is generally considered to be a significantly clean area owing to its high altitude; however, the transport of atmospheric pollutants from the Indian subcontinent to the Tibetan Plateau has influenced the Tibetan environments. Nyingchi is located at the end of an important water vapor channel. In this study, continuous monitoring of gaseous elemental mercury (GEM), gaseous oxidized mercury (GOM), and particle-bound mercury (PBM) was conducted in Nyingchi from 30 March to 3 September 2019, to study the influence of the Indian summer monsoon (ISM) on the origin, transport, and behavior of Hg. The GEM and PBM during the preceding Indian summer monsoon (PISM) period (1.20±0.35 ng m−3 and 11.4±4.8 pg m−3 for GEM and PBM, respectively) were significantly higher than those during the ISM period (0.95±0.21 ng m−3, and 8.8±6.0 pg m−3); the GOM during the PISM period (13.5±7.3 pg m−3) was almost at the same level as that during the ISM period (12.7±14.3 pg m−3). The average GEM concentration in the Nyingchi region, obtained using passive sampler, was 1.12±0.28 ng m−3 (from 4 April 2019 to 31 March 2020). The GEM concentration showed that the sampling area was very clean compared to other high-altitude sites. The GEM has several patterns of diurnal variation during different periods. Stable high GEM concentrations occur at night and low concentrations occur in the afternoon during PISM, which may be related to the nocturnal boundary layer structure. High values occurring in the late afternoon during the ISM may be related to long-range transport. Low concentrations of GEM observed during the morning in the ISM may originate from vegetation effects. The results of the trajectory model demonstrate that the sources of pollutants at Nyingchi are different with different circulation patterns. During westerly circulation in the PISM period, pollutants mainly originate from central India, northeastern India, and central Tibet. During the ISM period, the pollutants mainly originate from the southern part of the SET site. The strong precipitation and vegetation effects on Hg species during the ISM resulted in low Hg concentrations transmitted to Nyingchi during this period. Further, principal component analysis showed that long-distance transport, local emissions, meteorological factors, and snowmelt factors are the main factors affecting the local Hg concentration in Nyingchi. Long-distance transport factor dominates during PISM and ISM3, while local emissions is the major contributor between PISM and ISM3. Our results reveal the Hg species distribution and possible sources of the most important water vapor channel in the Tibetan Plateau and could serve as a basis for further transboundary transport flux calculations.

Variegated Outcomes of T Cell Activation by Dendritic Cells in the Steady State

Abstract: Abstract Conventional dendritic cells (cDC) control adaptive immunity by sensing damage- and pathogen-associated molecular patterns and then inducing defined differentiation programs in T cells. Nevertheless, in the absence of specific proimmunogenic innate signals, generally referred to as the steady state, cDC also activate T cells to induce specific functional fates. Consistent with the maintenance of homeostasis, such specific outcomes of T cell activation in the steady state include T cell clonal anergy, deletion, and conversion of peripheral regulatory T cells (pTregs). However, the robust induction of protolerogenic mechanisms must be reconciled with the initiation of autoimmune responses and cancer immunosurveillance that are also observed under homeostatic conditions. Here we review the diversity of fates and functions of T cells involved in the opposing immunogenic and tolerogenic processes induced in the steady state by the relevant mechanisms of systemic cDC present in murine peripheral lymphoid organs.

Can Non-Physician Providers Use Ultrasound to Aid in Establishing Peripheral IV Access in Patients Who are Difficult to Cannulate? A Scoping Review

Abstract: Non-physician performed point-of-care ultrasound (POCUS) is emerging as a diagnostic adjunct with the potential to enhance current practice. The scope of POCUS utility is broad and well-established in-hospital, yet limited research has occurred in the out-of-hospital environment. Many physician-based studies expound the value of POCUS in the acute setting as a therapeutic and diagnostic tool. This study utilized a scoping review methodology to map the literature pertaining to non-physician use of POCUS to improve success of peripheral intravenous access (PIVA), especially in patients predicted to be difficult to cannulate.Ovid MEDLINE, CINAHL Plus, EMBASE, and PubMed were searched from January 1, 1990 through April 15, 2021. A thorough search of the grey literature and reference lists of relevant articles was also performed to identify additional studies. Articles were included if they examined non-physician utilization of ultrasound-guided PIVA (USGPIVA) for patients anticipated to be difficult to cannulate.A total of 158 articles were identified. A total of 16 articles met the inclusion criteria. The majority of participants had varied experience with ultrasound, making accurate comparison difficult. Training and education were non-standardized, as was the approach to determining difficult intravenous access (DIVA). Despite this, the majority of the studies demonstrated high first attempt and overall success rates for PIVA performed by non-physicians.Non-physician USGPIVA appears to be a superior method for PIVA when difficulty is anticipated. Additional benefits include reduced requirement for central venous catheter (CVC) or intraosseous (IO) needle placement. Paramedics, nurses, and emergency department (ED) technicians are able to achieve competence in this skill with relatively little training. Further research is required to explore the utility of this practice in the out-of-hospital environment.

Multilevel barriers and facilitators of communication in pediatric oncology: A systematic review.

Abstract: Multiple factors can facilitate or impede the fulfillment of communication functions in pediatric cancer. In this systematic review, we evaluated 109 studies from the preceding 20 years that presented qualitative or quantitative evidence of barriers or facilitators to communication in pediatric cancer. Using a multilevel framework developed in our prior study, we then analyzed and categorized the levels of barriers and facilitators identified in included studies. The vast majority of studies focused on individual-level barriers, rather than team, organization/system, collaborating hospital, community, or policy-level barriers. Future studies should explore the full range of factors that affect communication.

wSDTNBI: a novel network-based inference method for virtual screening

Abstract: In recent years, the rapid development of network-based methods for the prediction of drug-target interactions (DTIs) provides an opportunity for the emergence of a new type of virtual screening (VS), namely, network-based VS. Herein, we reported a novel network-based inference method named wSDTNBI. Compared with previous network-based methods that use unweighted DTI networks, wSDTNBI uses weighted DTI networks whose edge weights are correlated with binding affinities. A two-pronged approach based on weighted DTI and drug-substructure association networks was employed to calculate prediction scores. To show the practical value of wSDTNBI, we performed network-based VS on retinoid-related orphan receptor γt (RORγt), and purchased 72 compounds for experimental validation. Seven of the purchased compounds were confirmed to be novel RORγt inverse agonists by in vitro experiments, including ursonic acid and oleanonic acid with IC50 values of 10 nM and 0.28 μM, respectively. Moreover, the direct contact between ursonic acid and RORγt was confirmed using the X-ray crystal structure, and in vivo experiments demonstrated that ursonic acid and oleanonic acid have therapeutic effects on multiple sclerosis. These results indicate that wSDTNBI might be a powerful tool for network-based VS in drug discovery.

Robotic-Assisted Video-Endoscopic Inguinal Lymphadenectomy (RAVEIL) and Video-Endoscopic Inguinal Lymphadenectomy (VEIL) versus Open Inguinal Lymph-Node Dissection (OILND) in carcinoma of penis: Comparison of perioperative outcomes, complications and oncological outcomes. A systematic review and meta-analysis

Abstract: To perform a systematic review and meta-analysis evaluating the peri-operative outcomes, complications, and oncological outcomes of Robotic-Assisted Video-Endoscopic Inguinal Lymphadenectomy (RAVEIL)/Video-Endoscopic Inguinal Lymphadenectomy (VEIL) with Open Inguinal Lymph-Node Dissection (OILND) for management of inguinal lymph-nodes in carcinoma of the penis.A comprehensive literature search was performed in January 2021 using the PubMed, Embase, and Cochrane databases. Data from human studies comparing RAVEIL/VEIL vs. OILND in carcinoma of penis published in English was extracted and analyzed by two independent authors.Two Randomised Controlled Trials and 6 cohort studies were included in the meta-analysis. RAVEIL/VEIL group exhibited increased operative time (Mean Difference [MD] = 15.28 [14.19; 16.38], P < 0.001), shorter hospital stay (MD = -1.06 [-1.14; -0.98], P < 0.001), and decreased duration of drainage (MD = -2.82 [-3.21; -2.43], P < 0.001), wound infection (Odds Ratio [OR] = 0.15 [0.08; 0.27], P < 0.001), skin necrosis (OR = 0.12 [0.05; 0.28], P < 0.001), lymphedema (OR = 0.41 [0.24; 0.72], P = 0.002), and major complications (OR = 0.11 [0.05; 0.24], P < 0.001) as compared to OILND group. Recurrence rate and number of deaths were comparable in both the groups. RAVEIL/VEIL groups showed slightly larger lymph-node yield (MD = 0.44 [0.18; 0.70], P < 0.001) as compared to OILND group.RAVEIL/VEIL has lesser skin complications, lymphedema, and better lymph-node yield as compared to OILND. It is comparable in terms of lymphocele and recurrence. It has lesser hospital stay and duration of drainage but owing to heterogeneity, the results should be interpreted with caution. Further studies are required to determine long-term oncological outcomes like overall survival and disease-specific survival.

Transition‐Metal‐Mediated Glycosylation with Thioglycosides

Abstract: Thioglycosides are among the most common glycosyl donors that find broad application in the synthesis of glycans and glycoconjugates. However, the requirement for toxic and/or large access of activators needed for common glycosylations with thioglycosides remains a notable drawback. Due to the increased awareness of the chemical waste impact on the environment, synthetic studies have been driven by the goal of finding non-toxic reagents. The main focus of this review is to highlight recent methods for thioglycoside activation that rely on transition metal catalysis.

Effects of Transcendental Meditation on Blood Pressure

Abstract: Background The World Health Organization estimates that 1.13 billion people worldwide have hypertension. Although pharmaceutical management of blood pressure is available, there are reasons why people prefer not to take medications including costs, adverse effects, and lack of access. Nonpharmacological healthy lifestyle methods are needed. One alternative method is transcendental meditation (TM). Objective The purpose of this study was to quantitatively synthesize the effects of TM on blood pressure. In addition, we examined the moderator effects of participant, methods, and intervention characteristics. Methods We searched 19 electronic databases without date restrictions to March 2021 including the gray literature and specific journals for primary studies evaluating TM to reduce blood pressure in adults and written in English. We coded primary studies for 5 categories (source, method, intervention, participant characteristics, and outcomes). Results Across 18 primary studies (N = 1207), TM mildly improved systolic blood pressure by −3.3 mm Hg (P = .025) and diastolic blood pressure by −1.8 mm Hg (P = .008) compared with comparison groups, but the effects waned after 3 months. Transcendental meditation reduced systolic blood pressure in samples that were 65 years and older significantly more than in samples that were younger than 65 years (−1.44 vs −9.87, P = .021) but showed no differential effect on diastolic blood pressure. Conclusions Transcendental meditation mildly reduced blood pressure, but the effect waned after 3 months. Adults older than 65 years benefited more than younger adults. Transcendental meditation might be recommended as one aspect of a healthy lifestyle.