Patient care in a neurointensive care unit (neuro-ICU) is challenging. Multidrug-resistant organisms (MDROs) are increasingly common in the routine clinical practice. We evaluated the impact of ...infection with MDROs on outcomes in patients with subarachnoid hemorrhage (SAH). A single-center retrospective analysis of SAH cases involving patients treated in the neuro-ICU was performed. The outcome was assessed 6 months after SAH using the modified Rankin Scale mRS, favorable (0-2) and unfavorable (3-6). Data were compared by matched-pair analysis. Patient characteristics were well matched in the MDRO (n = 61) and control (n = 61) groups. In this center, one nurse was assigned to a two-bed room. If a MDRO was detected, the patient was isolated, and the nurse was assigned to the patient infected with the MDRO. In the MDRO group, 29 patients (48%) had a favorable outcome, while 25 patients (41%) in the control group had a favorable outcome; the difference was not significant (p > 0.05). Independent prognostic factors for unfavorable outcomes were worse status at admission (OR = 3.1), concomitant intracerebral hematoma (ICH) (OR = 3.7), and delayed cerebral ischemia (DCI) (OR = 6.8). Infection with MRDOs did not have a negative impact on the outcome in SAH patients. Slightly better outcomes were observed in SAH patients infected with MDROs, suggesting the benefit of individual care.
Antiplatelet medication is required after stent-assisted coil embolization (SACE) to avoid thromboembolic complications. Currently, there is no consensus on how long the antiplatelet agent should be ...maintained. The authors investigated clinical outcomes in patients who discontinued their antiplatelet agent 12-24 months after SACE.
Data were retrieved from a prospective database for 373 consecutive patients with SACE at 6 institutions who discontinued antiplatelet therapy 12-24 months after SACE. Thromboembolic complications associated with discontinuation were defined as neurological or radiographic ischemia that occurred within 6 months after discontinuation of the antiplatelet agent; the lesion had to be correlated with the territory of the stented artery.
The mean time until discontinuation of the antiplatelet medication was 15.8 ± 4.7 months after SACE (12-18 months, n = 271; 19-24 months, n = 102). The most common location of treated aneurysms was the internal carotid artery (n = 223, 59.8%). A laser-cut open-cell stent was most commonly applied (n = 236/388, 60.8%), followed by laser-cut closed-cell stents (n = 119, 30.7%) and braided closed-cell (n = 33, 8.5%); double stenting was applied in 15 aneurysms. There were no patients who experienced cerebral ischemia related to discontinuation of antiplatelet medications, except for 1 patient at high risk of ischemia (0.27%, 95% CI 0.01%-1.48%).
These results suggest that it may be safe to discontinue antiplatelet medication after SACE in patients at low risk for ischemia, and that it appears safe to discontinue the agent at approximately 15 months after the procedure. Large cohort-based prospective studies or randomized clinical trials are warranted to confirm these results.
Introduction Marathon running is a popular recreational activity, but the effects of chronic running on the knee or other joints remain unclear. The purpose of this article was to evaluate any ...degenerative changes in the knees and spines of recreational runners who completed at least 1000 marathons. Methods Recreational runners who completed at least 1000 marathons were recruited. Magnetic resonance imaging (MRI) of both knees and spines of six such runners was performed with a 1.5 T MR scanner. The anatomical structures of the knee joint including meniscus, bone marrow, cartilage, ligaments, and joint effusion were examined along with other abnormalities. Spinal alignment, degenerative change in intervertebral disc, intervertebral disc herniation, osteoarthritis in facet joint, degenerative anterior/lateral spur, and other abnormalities were evaluated. Results In terms of knee joints, one runner showed degeneration at the meniscus, while three runners had cartilage lesions. However, none of the six runners showed radiologic evidence of knee osteoarthritis. All six runners demonstrated degenerative changes in intervertebral spinal discs. Conclusions Running 1000 marathons may not have a harmful effect on the knee joints and may not result in osteoarthritis. However, it is unclear whether degenerative changes in the spine are derived from running or aging.
Stem cell transplantation is emerging as a possible new treatment for liver cirrhosis, and recent animal studies have documented the benefits of stem cell therapy in a hepatic fibrosis model. ...However, the underlying mechanism of stem cell therapy is still unclear. Among the proposed mechanisms, the cell replacement mechanism is the oldest and most important, in which permanently damaged tissue can be replaced by normal tissue to restore function. In the present study, Cy5.5-labeled superparamagnetic iron oxide (SPIO) was used to label human mesenchymal stem cells. The uptake of fluorescently labeled nanoparticles enabled the detection and monitoring of the transplanted stem cells; therefore, we confirmed the direct incorporation and differentiation of SPIO into the hepatocyte-like transplanted stem cells by detecting human tyrosine aminotransferase (TAT), well-known enzymatic marker for hepatocyte-specific differentiation. KCI Citation Count: 3
Stem cell transplantation is emerging as a possible new treatment for liver cirrhosis, and recent animal studies have documented the benefits of stem cell therapy in a hepatic fibrosis model. ...However, the underlying mechanism of stem cell therapy is still unclear. Among the proposed mechanisms, the cell replacement mechanism is the oldest and most important, in which permanently damaged tissue can be replaced by normal tissue to restore function. In the present study, Cy5.5-labeled superparamagnetic iron oxide (SPIO) was used to label human mesenchymal stem cells. The uptake of fluorescently labeled nanoparticles enabled the detection and monitoring of the transplanted stem cells; therefore, we confirmed the direct incorporation and differentiation of SPIO into the hepatocyte-like transplanted stem cells by detecting human tyrosine aminotransferase (TAT), well-known enzymatic marker for hepatocyte-specific differentiation.
Despite the increased interest in secretomes associated with paracrine/autocrine mechanisms, the majority of mass spectrometric cell secretome studies have been performed using serum-free medium ...(SFM). On the other hand, serum-containing medium (SCM) is not recommended very much because the secretome obtained with SCM is easily contaminated with fetal bovine serum (FBS) proteins. In this study, through the combination of bioorthogonal non-canonical amino acid tagging (BONCAT) and pulsed-SILAC (pSILAC), we analyzed differentially secreted proteins between SFM and SCM in a cancer-derived human cell, U87MG, and a mesenchymal stem cell derived from human Wharton's jelly (hWJ-MSCs). In most cases, the bioinformatic tools predicted a protein to be truly secretory when the secretion level of the protein was more in SCM than in SFM. In the case of hWJ-MSCs, the amount of proteins secreted in SCM for 24 hours was larger than that of SFM (log
fold change = 0.96), even considering different cell proliferation rates. hWJ-MSCs proteins secreted more in SCM included several positive markers of MSC paracrine factors implicated in angiogenesis, neurogenesis and osteogenesis, and upstream regulators of cell proliferation. Our study suggests the analysis of the secretome should be processed in SCM that promotes cell proliferation and secretion.
Abstract
NMDA receptor (NMDAR) and GABA neuronal dysfunctions are observed in animal models of autism spectrum disorders, but how these dysfunctions impair social cognition and behavior remains ...unclear. We report here that NMDARs in cortical parvalbumin (Pv)-positive interneurons cooperate with gap junctions to promote high-frequency (>80 Hz) Pv neuronal burst firing and social cognition.
Shank2
–/–
mice, displaying improved sociability upon NMDAR activation, show impaired cortical social representation and inhibitory neuronal burst firing. Cortical
Shank2
–/–
Pv neurons show decreased NMDAR activity, which suppresses the cooperation between NMDARs and gap junctions (GJs) for normal burst firing.
Shank2
–/–
Pv neurons show compensatory increases in GJ activity that are not sufficient for social rescue. However, optogenetic boosting of Pv neuronal bursts, requiring GJs, rescues cortical social cognition in
Shank2
–/–
mice, similar to the NMDAR-dependent social rescue. Therefore, NMDARs and gap junctions cooperate to promote cortical Pv neuronal bursts and social cognition.
Mesenchymal stem cells (MSCs) are known to have therapeutic potential for cartilage repair. However, the optimal concentration of MSCs for cartilage repair remains unclear. Therefore, we aimed to ...explore the feasibility of cartilage repair by human umbilical cord blood-derived MSCs (hUCB-MSCs) and to determine the optimal concentrations of the MSCs in a rabbit model.
Osteochondral defects were created in the trochlear groove of femur in 55 rabbits. Four experimental groups (11 rabbits/group) were treated by transplanting the composite of hUCB-MSCs and HA with various MSCs concentrations (0.1, 0.5, 1.0, and 1.5 x 107 cells/ml). One control group was left untreated. At 4, 8, and 16 weeks post-transplantation, the degree of cartilage repair was evaluated grossly and histologically.
Overall, transplanting hUCB-MSCs and HA hydrogel resulted in cartilage repair tissue with better quality than the control without transplantation (P = 0.015 in 0.1, P = 0.004 in 0.5, P = 0.004 in 1.0, P = 0.132 in 1.5 x 107 cells/ml). Interestingly, high cell concentration of hUCB-MSCs (1.5×107 cells/ml) was inferior to low cell concentrations (0.1, 0.5, and 1.0 x 107 cells/ml) in cartilage repair (P = 0.394,P = 0.041, P = 0.699, respectively). The 0.5 x 107 cells/ml group showed the highest cartilage repair score at 4, 8 and 16 weeks post transplantation, and followed by 0.1x107 cells/ml group or 1.0 x 107 cell/ml group.
The results of this study suggest that transplantation of the composite of hUCB-MSCs and HA is beneficial for cartilage repair. In addition, this study shows that optimal MSC concentration needs to be determined for better cartilage repair.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Plasma, formed by ionization of gas molecules or atoms, is the most abundant form of matter and consists of highly reactive physicochemical species. In the physics and chemistry fields, plasma has ...been extensively studied; however, the exact action mechanisms of plasma on biological systems, including cells and humans, are not well known. Recent evidence suggests that cold atmospheric plasma (CAP), which refers to plasma used in the biomedical field, may regulate diverse cellular processes, including neural differentiation. However, the mechanism by which these physicochemical signals, elicited by reactive oxygen and nitrogen species (RONS), are transmitted to biological system remains elusive. In this study, we elucidated the physicochemical and biological (PCB) connection between the CAP cascade and Trk/Ras/ERK signaling pathway, which resulted in neural differentiation. Excited atomic oxygen in the plasma phase led to the formation of RONS in the PCB network, which then interacted with reactive atoms in the extracellular liquid phase to form nitric oxide (NO). Production of large amounts of superoxide radical (O2−) in the mitochondria of cells exposed to CAP demonstrated that extracellular NO induced the reversible inhibition of mitochondrial complex IV. We also demonstrated that cytosolic hydrogen peroxide, formed by O2− dismutation, act as an intracellular messenger to specifically activate the Trk/Ras/ERK signaling pathway. This study is the first to elucidate the mechanism linking physicochemical signals from the CAP cascade to the intracellular neural differentiation signaling pathway, providing physical, chemical and biological insights into the development of therapeutic techniques to treat neurological diseases.
Kawasaki disease (KD), a systemic vasculitis of infants and children, manifests as fever and mucocutaneous inflammation. Although its etiology is largely unknown, the epidemiological data suggest ...that genetic factors are important in KD susceptibility. To identify genetic variants influencing KD susceptibility, we performed a genome-wide association study (GWAS) and replication study using a total of 915 children with KD and 4553 controls in the Korean population. Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with KD susceptibility (P<1.0 × 10
), including the previously reported BLK locus (rs6993775, odds ratio (OR)=1.52, P=2.52 × 10
). The other two loci were newly identified: NMNAT2 on chromosome 1q25.3 (rs2078087, OR=1.33, P=1.15 × 10
) and the human leukocyte antigen (HLA) region on chromosome 6p21.3 (HLA-C, HLA-B, MICA and HCP5) (rs9380242, rs9378199, rs9266669 and rs6938467; OR=1.33-1.51, P=8.93 × 10
to 5.24 × 10
). Additionally, SNP rs17280682 in NLRP14 was associated significantly with KD with a family history (18 cases vs 4553 controls, OR=6.76, P=5.46 × 10
). These results provide new insights into the pathogenesis and pathophysiology of KD.
PDF
