The effects of Korean red ginseng extract (KRGE) on autoimmune disorders of the nervous system are not clear. We investigated whether KRGE has a beneficial effect on acute and chronic experimental ...autoimmune encephalomyelitis (EAE). Pretreatment (daily from 10 days before immunization with myelin basic protein peptide) with KRGE significantly attenuated clinical signs and loss of body weight and was associated with the suppression of spinal demyelination and glial activation in acute EAE rats, while onset treatment (daily after the appearance of clinical symptoms) did not. The suppressive effect of KRGE corresponded to the messenger RNA (mRNA) expression of proinflammatory cytokines (tumor necrosis factor-α TNF-α and interleukin IL-1β), chemokines (RANTES, monocyte chemotactic protein-1 MCP-1, and macrophage inflammatory protein-1α MIP-1α), adhesion molecules (intercellular adhesion molecule-1 ICAM-1, vascular cell adhesion molecule-1 VCAM-1, and platelet endothelial cell adhesion molecule PECAM-1), and inducible nitric oxide synthase in the spinal cord after immunization. Interestingly, in acute EAE rats, pretreatment with KRGE significantly reduced the population of CD4
+
, CD4
+
/IFN-γ
+
, and CD4
+
/IL-17
+
T cells in the spinal cord and lymph nodes, corresponding to the downregulation of mRNA expression of IFN-γ, IL-17, and IL-23 in the spinal cord. On the other hand, KRGE pretreatment increased the population of CD4
+
/Foxp3
+
T cells in the spinal cord and lymph nodes of these rats, corresponding to the upregulation of mRNA expression of Foxp3 in the spinal cord. Interestingly, intrathecal pretreatment of rats with ginsenosides (Rg1 and Rb1) significantly decreased behavioral impairment. These results strongly indicate that KRGE has a beneficial effect on the development and progression of EAE by suppressing T helper 1 (Th1) and Th17 T cells and upregulating regulatory T cells. Additionally, pre- and onset treatment with KRGE alleviated neurological impairment of myelin oligodendrocyte glycoprotein
35–55
-induced mouse model of chronic EAE. These results warrant further investigation of KRGE as preventive or therapeutic strategies for autoimmune disorders, such as multiple sclerosis.
A vertebral fracture is the most common type of osteoporotic fracture. Osteoporotic vertebral fractures (OVFs) cause a variety of morbidities and deaths. There are currently few "gold standard ...treatments" outlined for the management of OVFs in terms of quantity and quality. Conservative treatment is the primary treatment option for OVFs. The treatment of pain includes short-term bed rest, analgesic medication, anti-osteoporotic medications, exercise, and a brace. Numerous reports have been made on studies for vertebral augmentation (VA), including vertebroplasty and kyphoplasty. There is still debate and controversy about the effectiveness of VA in comparison with conservative treatment. Until more robust data are available, current evidence does not support the routine use of VA for OVF. Despite the fact that the majority of OVFs heal without surgery, 15%-35% of patients with an unstable fracture, persistent intractable back pain, or severely collapsed vertebra that causes a neurologic deficit, kyphosis, or chronic pseudarthrosis frequently require surgery. Because no single approach can guarantee the best surgical outcomes, customized surgical techniques are required. Surgeons must stay current on developments in the osteoporotic spine field and be open to new treatment options. Osteoporosis management and prevention are critical to lowering the risk of future OVFs. Clinical studies on bisphosphonate's effects on fracture healing are lacking. Teriparatide was intermittently administered, which dramatically improved spinal fusion and fracture healing while lowering mortality risk. According to the available literature, there are no standard management methods for OVFs. More multimodal approaches, including conservative and surgical treatment, VA, and medications that treat osteoporosis and promote fracture healing, are required to improve the quality of the majority of guidelines.
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are an important family of catalytic enzymes that generate reactive oxygen species (ROS), which mediate the regulation of diverse ...cellular functions. Although phagocyte Nox2/gp91phox is closely associated with the activation of host innate immune responses, the roles of Nox family protein during Toxoplasma gondii (T. gondii) infection have not been fully investigated. Here, we found that T. gondii-mediated ROS production was required for the upregulation of macrophage migration inhibitory factor (MIF) mRNA and protein levels via activation of mitogen-activated protein kinase and nuclear factor-κB signaling in macrophages. Interestingly, MIF knockdown led to a significant increase in the survival of intracellular T. gondii in bone marrow-derived macrophages (BMDMs). Moreover, Nox4 deficiency, but not Nox2/gp91phox and the cytosolic subunit p47phox, resulted in enhanced survival of the intracellular T. gondii RH strain and impaired expression of T. gondii-mediated MIF in BMDMs. Additionally, Nox4-deficient mice showed increased susceptibility to virulent RH strain infection and increased cyst burden in brain tissues and low levels of MIF expression following infection with the avirulent ME49 strain. Collectively, our findings indicate that Nox4-mediated ROS generation plays a central role in MIF production and resistance to T. gondii infection.
Neoadjuvant chemotherapy (NACT) followed by total mastectomy and immediate reconstruction has become an important strategy in the treatment of breast cancer. Although the safety of subpectoral ...implant-based breast reconstruction with NACT has been extensively evaluated, the safety in prepectoral reconstruction has not been clearly elucidated. We aimed to evaluate the association of NACT with immediate prepectoral breast reconstruction outcomes.
A retrospective review of patients who underwent total mastectomy and immediate implant-based prepectoral breast reconstruction between May and December 2021 was conducted. Patients were categorized into 2 groups: those receiving NACT and those not receiving it. Postoperative complication rates were compared between the 2 groups. The independent association between NACT and the complication profiles was evaluated. Propensity score matching was also conducted.
We analyzed 343 cases, including 85 who received NACT treatment and 258 who did not. Compared with the non-NACT group, the NACT group was younger, had a higher body mass index, and a higher rate of adjuvant radiotherapy. There were no differences in the rates of overall complications or type of complication between the 2 groups. In the multivariable logistic analyses, NACT did not show a significant association with the development of adverse outcomes. Similar results were observed in propensity score matching analyses.
Our results suggest that receiving NACT may not have a significant detrimental effect on the postoperative outcomes of immediate prepectoral prosthetic reconstructions. Conducting prepectoral implant-based reconstruction in the setting of NACT might be safe and provide acceptable outcomes.
Suspended particulate matter (SPM) is abundant and essential in marine and coastal waters, and comprises a wide variety of biomineral particles, which are practically grouped into organic biomass and ...inorganic sediments. Such biomass and sediments interact with each other and build large biomineral aggregates via flocculation, therefore controlling the fate and transport of SPM in marine and coastal waters. Despite its importance, flocculation mediated by biomass-sediment interactions is not fully understood. Thus, the aim of this research was to explain biologically mediated flocculation and SPM dynamics in different locations and seasons in marine and coastal waters. Field measurement campaigns followed by physical and biochemical analyses had been carried out from 2004 to 2011 in the Belgian coastal area to investigate bio-mediated flocculation and SPM dynamics. Although SPM had the same mineralogical composition, it encountered different fates in the turbidity maximum zone (TMZ) and in the offshore zone (OSZ), regarding bio-mediated flocculation. SPM in the TMZ built sediment-enriched, dense, and settleable biomineral aggregates, whereas SPM in the OSZ composed biomass-enriched, less dense, and less settleable marine snow. Biological proliferation, such as an algal bloom, was also found to facilitate SPM in building biomass-enriched marine snow, even in the TMZ. In short, bio-mediated flocculation and SPM dynamics varied spatially and seasonally, owing to biomass-sediment interactions and bio-mediated flocculation.
P-type tin monoxide (SnO) decorated TiO2 nanoparticles have been synthesized by the powder atomic layer deposition (p-ALD) method in a fluidized bed reactor at 150–250 °C. Successful deposition of ...SnO on a TiO2 surface was realized using a precursor combination of Sn(dmamp)2 and H2O as Sn source and reactant, respectively. Prepared SnO/TiO2 nanoparticles were characterized by XRF, XPS, XRD, and TEM-EDS. Formation of a p-SnO/n-TiO2 heterojunction resulted in improved photocatalytic methylene blue degradation performance compared to using a TiO2 photocatalyst, which might be attributed to facile separation of photo-induced electron-hole pairs as well as to increased UV/visible light absorption by adopting a narrow bandgap SnO.
•SnO-decorated TiO2 nanoparticle was synthesized by powder atomic layer deposition.•SnO/TiO2 showed enhanced methylene blue degradation performance compared to TiO2 catalyst.•Photocatalytic methylene blue degradation mechanism of SnO/TiO2 was proposed.
Both skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) have been widely adopted. Although postmastectomy radiation therapy (PMRT) can improve clinical outcomes, it can worsen cosmesis ...following reconstruction. Therefore, identifying risk factors of ipsilateral breast tumor recurrence (IBTR) could help de-escalate PMRT after NSM/SSM in patients with pT1-2 disease.
We retrospectively reviewed patients treated with SSM (N = 400) and NSM (N = 156) in patients with pT1-2N0-1 disease between 2009 and 2016. Seventy-four patients received PMRT with 50–50.4 Gy in 25–28 fractions. The Cox proportional hazards model was used to analyze the prognostic factors of IBTR.
With a median follow-up of 66.2 months, 17 IBTR events were observed, with 5-year IBTR-free rate of 97.2%. Although only one IBTR was observed after PMRT, there was no statistical difference in the 5-year IBTR-free rate (PMRT vs. no PMRT, 98.6% vs. 97.0%, p = 0.360). Multivariable analyses demonstrated that age ≤45 years and lymphovascular invasion (LVI) were adverse features of IBTR. The low-risk group (0 risk factor) showed a better 5-year IBTR-free rate than the high-risk group (≥1 risk factor) (100.0% vs. 95.8%, p = 0.003). In the high-risk group, PMRT slightly improved 5-year IBTR-free rate compared with no PMRT (98.6% vs. 95.2%, p = 0.166). In addition, PMRT increased 5-year cumulative incidence of reconstruction failure (10.0% vs. 2.8%, p = 0.001).
We identified risk factors (age and LVI) related to IBTR following upfront SSM/NSM with pT1-2 disease. As a hypothesis-generating study, de-escalation of PMRT by omitting chest wall irradiation in selective patients could improve reconstruction-related complications without compromising oncologic outcomes.
•IBTR-free rate at 5 years after SSM/NSM in pT1-2N0-1 disease was 97.2%.•Age ≤45 years and tumor with LVI were associated with increased IBTR rate.•Omitting chest wall RT to selective patients could improve reconstruction outcomes.
•Lead exposure during gestational period deteriorate normal development of cerebellum in pups.•In the postnatal developing cerebellum of rats, lead exposure increased the apoptotic cell deaths and ...reduced the number of Purkinje cells.•Ascorbic acid treatment is effective in reducing the lead-induced changes in Purkinje cells and apoptotic death by reducing pro-apoptotic bax and oxidative stress in the developing cerebellum.
We investigated the effects of the gestational administration of lead (Pb) and ascorbic acid on cerebellar development. Pregnant female rats were randomly assigned to the control, Pb, or Pb plus ascorbic acid (PA) groups; six offspring per cage were randomly selected for analysis. Compared to the control group, fewer Purkinje cells were observed in the Pb-exposed pups at postnatal day 21. However, co-administrating Pb and ascorbic acid inhibited the Pb-induced reduction in Purkinje cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, which detected DNA fragmentation in the dying cells, showed more TUNEL-positive cells in the Pb group, while co-treatment with Pb and ascorbic acid mitigated the Pb-induced cellular degeneration. Using immunohistochemistry and immunoblotting, we additionally found that Pb exposure induced a rise in the apoptotic factor Bax in the cerebellum, while Pb plus ascorbic acid treatment ameliorated this Bax induction. Since, Pb competes with the iron in the cell and the accumulation of free iron triggers oxidative stress, we performed iron staining, which revealed that ascorbic acid prevented the Pb-induced rises in iron-reactive cells and iron-reactivity. The anti-oxidant enzyme manganese-dependent superoxide dismutase showed change patterns that were similar to those of iron in the cerebellum. Finally, the pups’ blood Pb levels were highest in the Pb group but were reduced in the PA group. Our findings suggest that ascorbic acid effectively ameliorates Pb-induced apoptosis and oxidative stress in the cerebellum. The present results imply that ascorbic acid treatment during pregnancy may protect against Pb-mediated developmental impairments in the cerebellum.
Bimodal flocculation of marine and estuarine sediments describes the aggregation and breakage process in which dense microflocs and floppy macroflocs change their relative mass fraction and develop a ...bimodal floc size distribution. To simulate bimodal flocculation of such sediments, a Two-Class Population Balance Equation (TCPBE), which includes both size-fixed microflocs and size-varying macroflocs, was developed. The new TCPBE was tested by a model-data fitting analysis with experimental data from 1-D column tests, in comparison with the simple Single-Class PBE (SCPBE) and the elaborate Multi-Class PBE (MCPBE). Results showed that the TCPBE was the simplest model that is capable of simulating the major aspects of the bimodal flocculation of marine and estuarine sediments. Therefore, the TCPBE can be implemented in a large-scale multi-dimensional flocculation model with least computational cost and used as a prototypic model for researchers to investigate complicated cohesive sediment transport in marine and estuarine environments. Incorporating additional biological and physicochemical aspects into the TCPBE flocculation process is straight-forward also.
► Bimodal flocculation causes a bimodal floc size distribution consisting of microflocs and macroflocs. ► We develop a Two-Class Population Balance Equation (TCPBE) to simulate bimodal flocculation. ► We test the TCPBE in a model-data fitting analysis with data obtained from 1-D column tests. ► The TCPBE is the simplest model capable of simulating bimodal flocculation.
In the posterior instrumented fusion surgery for thoracolumbar (T-L) burst fracture, early postoperative re-collapse of well-reduced vertebral body fracture could induce critical complications such ...as correction loss, posttraumatic kyphosis, and metal failure, often leading to revision surgery. Furthermore, re-collapse is quite difficult to predict because of the variety of risk factors, and no widely accepted accurate prediction systems exist. Although load-sharing classification has been known to help to decide the need for additional anterior column support, this radiographic scoring system has several critical limitations.
(1) To evaluate risk factors and predictors for postoperative re-collapse in T-L burst fractures. (2) Through the decision-making model, we aimed to predict re-collapse and prevent unnecessary additional anterior spinal surgery.
Retrospective comparative study.
Two-hundred and eight (104 men and 104 women) consecutive patients with T-L burst fracture who underwent posterior instrumented fusion were reviewed retrospectively. Burst fractures caused by high-energy trauma (fall from a height and motor vehicle accident) with a minimum 1-year follow-up were included. The average age at the time of surgery was 45.9 years (range, 15–79). With respect to the involved spinal level, 95 cases (45.6%) involved L1, 51 involved T12, 54 involved L2, and 8 involved T11. Mean fixation segments were 3.5 (range, 2–5). Pedicle screw instrumentation including fractured vertebra had been performed in 129 patients (62.3%).
Clinical data using self-report measures (visual analog scale score), radiographic measurements (plain radiograph, computed tomography, and magnetic resonance image), and functional measures using the Oswestry Disability Index were evaluated.
Body height loss of fractured vertebra, body wedge angle, and Cobb angle were measured in serial plain radiographs. We assigned patients to the re-collapse group if their body height loss progressed greater than 20% at any follow-up time compared with immediate postoperative body height loss; we assigned the remaining patients to the well-maintained group. The chi-square test and t test of SPSS were used for comparison of differences between two groups and multiple logistic regression analysis for risk factor evaluation. Through the decision tree analysis of statistical package R, a decision-making model was composed, and a cutoff value of revealed risk factors and re-collapse rate of each subgroup were identified. The present study wassupported by the University College of Medicine Research Fund (university to which authors belong). There was no external funding source for this study. The authors have no conflict of interest to declare.
Re-collapse occurred in 31 of 208 patients (14.9%). In this group, age, the proportion of male gender, preoperative height loss, and preoperative wedge angle were significantly greater than the well-maintained group. Multivariable logistic regression analysis identified two independent risk factors: age (adjusted odds ratio 1.084, p=.002) and body height loss (adjusted odds ratio 1.065, p=.003). According to the decision-making tree, age (>43 years) was the most discriminating variable, andpreoperative body height loss (>54%) was the second. In this model, the re-collapse rate was zero in ages less than 43 years, and among those remaining, nearly 80% patients with greater than 54% of body height loss belonged to the re-collapse group.
The independent predictors of re-collapse after posterior instrumented fusion for T-L burst fracture were the age at operation (>43 years old) and preoperative body height loss (>54%). Careful assessment using our decision-making model could help to predict re-collapse and prevent unnecessary additional spinal surgery for anterior column support, especially in young patients.
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