Multifunctional effects of Lactobacillus sakei HEM 224 on the gastrointestinal tract and airway inflammation.

Mucosal tissues serve as the first defense line and their commensal microbiota play a role in sustaining of host health. This study aimed to isolate and evaluate a putative probiotic strain on various mucosal regions. Lactobacillus sakei HEM 224 was isolated from traditional Korean kimchi and identified. In the safety assessment L. sakei HEM 224 showed negative results for hemolysis, biogenic amine production and transferable antibiotic resistance. The probiotic potential of strain HEM 224 in diverse mucosal areas was shown in two different models, viz. a murine model with colitis induced by dextran sulfate sodium (DSS) and an allergic airway inflammation model induced by ovalbumin (OVA). In the colitis model, oral administration of L. sakei HEM 224 improved colitis physiology with immunomodulation, enhancing barrier components and gut microbiota alteration. In the allergic airway inflammation model, the intranasal administration of the strain decreased type 2 inflammation and enhanced epithelial barrier integrity from the airways. These results demonstrate that L. sakei HEM 224 can ameliorate inflammatory conditions in both the gastrointestinal and respiratory tracts through the reinforcement of the epithelial barrier and immunomodulation.

Macrophages promote Fibrinogenesis during kidney injury.

Macrophages (Mø) are widely considered fundamental in the development of kidney fibrosis since Mø accumulation commonly aggravates kidney fibrosis, while Mø depletion mitigates it. Although many studies have aimed to elucidate Mø-dependent mechanisms linked to kidney fibrosis and have suggested various mechanisms, the proposed roles have been mostly passive, indirect, and non-unique to Mø. Therefore, the molecular mechanism of how Mø directly promote kidney fibrosis is not fully understood. Recent evidence suggests that Mø produce coagulation factors under diverse pathologic conditions. Notably, coagulation factors mediate fibrinogenesis and contribute to fibrosis. Thus, we hypothesized that kidney Mø express coagulation factors that contribute to the provisional matrix formation during acute kidney injury (AKI). To test our hypothesis, we probed for Mø-derived coagulation factors after kidney injury and uncovered that both infiltrating and kidney-resident Mø produce non-redundant coagulation factors in AKI and chronic kidney disease (CKD). We also identified F13a1, which catalyzes the final step of the coagulation cascade, as the most strongly upregulated coagulation factor in murine and human kidney Mø during AKI and CKD. Our in vitro experiments revealed that the upregulation of coagulation factors in Mø occurs in a Ca2 + -dependent manner. Taken together, our study demonstrates that kidney Mø populations express key coagulation factors following local injury, suggesting a novel effector mechanism of Mø contributing to kidney fibrosis.

Interleukin-34-regulated T-cell responses in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a multifaceted etiology, which primarily affects and results in the deterioration of the synovium of patients. While the exact etiology of RA is still largely unknown, there is growing interest in the cytokine interleukin-34 (IL-34) as a driver or modulator of RA pathogenesis on the grounds that IL-34 is drastically increased in the serum and synovium of RA patients. Several studies have so far revealed the relationship between IL-34 levels and RA disease progression. Nevertheless, the significance and role of IL-34 in RA have remained ambiguous, as illustrated by two most recent studies, which reported contrasting effects of genetic IL-34 deletion in RA. Of note, IL-34 is a macrophage growth factor and is increasingly perceived as a master regulator of T-cell responses in RA via macrophage-dependent as well as T cell-intrinsic mechanisms. In this regard, several studies have demonstrated that IL-34 potentiates helper T-cell (Th) responses in RA, whereas studies also suggested that IL-34 alleviates synovial inflammation, potentially by inducing regulatory T-cells (Treg). Herein, we provide an overview of the current understanding of IL-34 involvement in RA and outline IL-34-mediated mechanisms in regulating T-cell responses in RA.

Development of Neuropathic Arthropathy With Entrectinib: Case Report.

TRK inhibition can lead to on-target neurologic adverse events. Two cases illustrate the development of neuropathic arthropathy as a side effect of entrectinib. After starting entrectinib, both patients developed foot pain, swelling, and sensory changes with magnetic resonance imaging revealing marrow edema. Providers should have a low threshold to investigate foot pain or gait abnormalities thoroughly with magnetic resonance imaging and referral to specialists to aid in the diagnosis of neuropathic arthropathy, with consideration to transition to an alternative agent.

The Therapeutic Potential of Anticoagulation in Organ Fibrosis.

Fibrosis, also known as organ scarring, describes a pathological stiffening of organs or tissues caused by increased synthesis of extracellular matrix (ECM) components. In the past decades, mounting evidence has accumulated showing that the coagulation cascade is directly associated with fibrotic development. Recent findings suggest that, under inflammatory conditions, various cell types (e.g., immune cells) participate in the coagulation process causing pathological outcomes, including fibrosis. These findings highlighted the potential of anticoagulation therapy as a strategy in organ fibrosis. Indeed, preclinical and clinical studies demonstrated that the inhibition of blood coagulation is a potential intervention for the treatment of fibrosis across all major organs (e.g., lung, liver, heart, and kidney). In this review, we aim to summarize our current knowledge on the impact of components of coagulation cascade on fibrosis of various organs and provide an update on the current development of anticoagulation therapy for fibrosis.

Inferior and Intra-/Peri-Articular Superior Sacroiliac Joint Injection Approaches Under Ultrasound Guidance to Treat Metastasis-Related Posterior Pelvic Bone Pain.

BACKGROUND: Numerous mechanical and pathologic variables contribute to sacroiliac joint (SIJ) pain. The oncologic population has additional considerations, including tumor burden causing fracture, nerve compression, joint instability, and periosteal inflammation. Post-treatment changes may also restrict joint mobility, causing transitional pain. Currently, fluoroscopically guided SIJ injections, aimed at the inferior one third of the SIJ, are the gold standard for treatment but have only been described in the nononcologic population. Ultrasound (US) guidance may confer several benefits, including positioning, ease of procedure, lower costs, and, importantly, guidance to avoid neovascularization, metastatic disease, and other soft tissue structures. OBJECTIVES: We aim to describe the advantages of US-guided SIJ injections for refractory malignant SIJ pain from extra-articular tumors. We then describe our technique and decision framework for accessing the superior or inferior SIJ in patients with metastatic sacroiliac pain. METHODS: A retrospective review was performed on 5 patients with refractory malignant SIJ pain who underwent US-guided superior or inferior approach SIJ injection. Using imaging and outcomes, we developed a decision framework. RESULTS: Patients received either inferior or superior approach SIJ injections depending on location of tumor, extent of tumor invasion, and stability of the SIJ as per our framework. All patients reported improvement in pain and function without complications. CONCLUSIONS: We propose a decision framework for inferior vs. superior approach US-guided SIJ injections in the oncologic population with SIJ pain from metastases to the pelvis or sacrum. Having multiple techniques to approach the SIJ is important in the oncologic population, in whom metastatic tumor burden poses a technical challenge to performing these injections.

Winter Adaptive Sports Participation, Injuries, and Equipment.

As the participation rate and popularity of winter adaptive sports increases, understanding injury patterns and equipment is crucial for athletes, coaches, athletic trainers, sports physicians, prosthetists/orthotists, and all the staff involved. While the inaugural Winter Paralympics in 1976 had 17 participating countries, the most recent paralympic games in Pyeongchang, South Korea had >500 athletes from 49 different countries competing in 6 disciplines: alpine skiing, nordic skiing, sledge hockey, wheelchair curling, biathlon, and snowboarding. In this paper, we review participation rates, injury trends and equipment, with a focus on the 3 most popular events: alpine skiing, nordic skiing, and sledge hockey. Despite injury risk within this athletic community, there are documented advantages to physical movement, and for each individual the risks of injury have to be weighted with the benefits of competing. Overall, there is a need for educational efforts regarding the development, access, and participation to injury prevention programs with an integrated and multidisciplinary approach.

Comparing Effects of Two Different Types of Nei-Guan Acupuncture Stimulation Devices in Reducing Postoperative Nausea and Vomiting.

PURPOSE: To compare the effects of a relief band using transcutaneous electrical nerve stimulation with a wrist band using acupressure on the Nei-Guan acupuncture point to relieve postoperative nausea and vomiting (PONV) in patients who had undergone gynecologic surgery. DESIGN: A double-blinded randomized controlled trial. METHODS: In total, 54 patients scheduled for gynecologic surgery under general anesthesia were included in this study. Assessments of PONV were performed 0, 2, 6, and 24 hours after discharge from the postanesthesia care unit. The severity of PONV was measured using the Rhodes' Index of Nausea, Vomiting and Retching and by recording the frequency of patient-requested antiemetic administration that is used to treat severe cases of PONV. FINDINGS: The relief band reduced the severity of PONV and the need for antiemetic administration within the first 24 hours postsurgery. CONCLUSIONS: The results of this study support the use of a relief band when compared with a wrist band and with a control group to reduce PONV in women after gynecologic surgery.

Satisficing in split-second decision making is characterized by strategic cue discounting.

Much of our real-life decision making is bounded by uncertain information, limitations in cognitive resources, and a lack of time to allocate to the decision process. It is thought that humans overcome these limitations through satisficing, fast but "good-enough" heuristic decision making that prioritizes some sources of information (cues) while ignoring others. However, the decision-making strategies we adopt under uncertainty and time pressure, for example during emergencies that demand split-second choices, are presently unknown. To characterize these decision strategies quantitatively, the present study examined how people solve a novel multicue probabilistic classification task under varying time pressure, by tracking shifts in decision strategies using variational Bayesian inference. We found that under low time pressure, participants correctly weighted and integrated all available cues to arrive at near-optimal decisions. With increasingly demanding, subsecond time pressures, however, participants systematically discounted a subset of the cue information by dropping the least informative cue(s) from their decision making process. Thus, the human cognitive apparatus copes with uncertainty and severe time pressure by adopting a "drop-the-worst" cue decision making strategy that minimizes cognitive time and effort investment while preserving the consideration of the most diagnostic cue information, thus maintaining "good-enough" accuracy. This advance in our understanding of satisficing strategies could form the basis of predicting human choices in high time pressure scenarios. (PsycINFO Database Record

Overclaiming and the medial prefrontal cortex: A transcranial magnetic stimulation study.

The tendency to claim more knowledge than one actually has is common and well documented; however, little research has focused on the neural mechanisms that underlie this phenomenon. The goal of the present study was to investigate the cortical correlates of overclaiming. Transcranial magnetic stimulation (TMS) was delivered to the medial prefrontal cortex (MPFC), supplementary motor area, and precuneus during the presentation of a series of words that participants were told made up a cultural IQ test. However, participants were not informed that 50% of the words were actually fabricated. False claiming was reduced following MPFC TMS. Furthermore, reaction time decreases following MPFC TMS indicated that participants engaged in less reflection during the task, suggesting a potential reduction in social monitoring of behavior.