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A 6-year-old, spayed, female, domestic shorthair cat presented with a 4-month history of chronic intermittent vomiting and anorexia. The haematologic results indicated moderate anaemia and a circulating mast cell population. The abdominal radiography revealed a markedly enlarged spleen. The cytological analysis of the spleen showed a uniform population of mast cells, and a diagnosis of systemic mastocytosis (splenic mast cell tumour with mastocytaemia) was made. This diagnosis was subsequently confirmed by the histopathological examination of the spleen. The immunohistochemistry for KIT showed KIT pattern II (focal cytoplasmic expression). A splenectomy and chemotherapy with vinblastine and prednisolone resulted in remission of the anaemia and other clinical signs. This case report highlights the importance of cytological evaluations of peripheral blood smears and/or aspirates of enlarged spleens for diagnosing splenic mast cell tumours and for quickly initiating the appropriate treatment.

Lumbar decompressive laminectomy is a standard treatment for degenerative lumbar spinal stenosis, but in some cases, can lead to iatrogenic spondylolysis and delayed segmental instability. Iatrogenic spondylolysis occurs in most cases in pars interarticularis, but rare cases have also been reported, pediculolysis in pedicle and laminolysis in lamina. Minimally invasive spine surgery (MIS) is known to have a low risk of developing these iatrogenic spondylolyses, and unilateral biportal endoscopy is the MIS that has been drawing attention. We present a case of a 72-year-old female who was diagnosed with L4-5 unstable non-isthmic spondylolisthesis and severe right central disc extrusion 10 weeks after UBE assisted unilateral laminotomy for bilateral decompression (ULBD) at the consecutive segments of L3-4 and L4-5. Pre-operative imaging studies revealed severe central stenosis without spondylolisthesis at L3-L4 and L4- L5 along with L4-L5 facet tropism. She was managed by anterior lumbar interbody fusion and cement augmented pedicle screw fixation, which resulted in the complete resolution of her clinical and neurologic symptoms.

Seon Yeong Chae,1 Min Chan Shin,2 Sangheon Jeon,2 Moon Sung Kang,2 Dong-Wook Han,2 Suck Won Hong2 1Research Center for Dielectric and Advanced Matter Physics, Pusan National University, Busan, 46241, Republic of Korea; 2Department of Cogno-Mechatronics Engineering, Department of Optics and Mechatronics Engineering, College of Nanoscience and Nanotechnology, Pusan National University, Busan, 46241, Republic of KoreaCorrespondence: Suck Won Hong Email swhong@pusan.ac.krBackground: The excellent physicochemical properties of graphene-based materials, including graphene oxide (GO) and reduced GO (rGO), offer significant technological potential as multifunctional nanomaterials in biomedical fields. Lutein is a type of carotenoid that forms human macular pigments in the retina, where it inhibits harmful blue light and contributes to the strengthening of the antioxidant defense of retinal pigment epithelium cells.Methods: Synthesis of the Lutein-rGO (Lu–rGO) complex was carried out for the optimized concentration. Then characterization of material was analyzed through ultraviolet-visible spectrophotometer (UV-Vis spectra), Fourier-transform infrared spectroscopy (FT-IR), Raman spectroscopy, x-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM). Antioxidant activity of Lu–rGO complex was measured by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2.2-diphenyl-1-picrylhydrazyl (DPPH), glutathione (GSH) oxidation assay. Then, oxidative stress induction by blue light and analyzed intracellular reactive oxygen species (ROS).Results and Conclusion: Based on the FT-IR measurement, the reduction efficiency defined by area was found to be 87.3%, the ID/IG ratio of 0.98 demonstrated by the Lu–rGO complex in the Raman spectrum was slightly higher than that of the original GO. The exhibited significant decrease in the peak intensities of the oxygen functional groups of the XPS spectra of the Lu–rGO complex was observed compared with the GO. In the TEM image for the Lu–rGO complex, folded and wrinkled nanostructures over the lutein-covered rGO surface were evidenced by tight molecular binding. The Lu–rGO complex provided superior DPPH and ABTS radical scavenging activity than GO and lutein alone, and the oxidation of GSH was suppressed. It was confirmed that the content of intracellular ROS and lysosomes, increased by blue light, was reduced after treatment with the Lu–rGO complex on ARPE-19 cells. In summary, graphene-based nanocarriers could function as preventative antioxidants during photochemical ROS generation based on the mechanism of antioxidant action.Keywords: reduced graphene oxide, lutein, antioxidant, blue light, nanocarrier

Focal myositis is a rare disease defined by an isolated inflammatory pseudotumour usually restricted to one skeletal muscle. Approximately, 250 cases of focal myositis have been described in the literature, and two recent large cohorts have been used to help in the diagnosis. Isolated gastrocnemius myositis, a rare immune-mediated condition, is a diagnostic entity used by internal medicine clinician in the gastrocnemius myalgia syndrome associated with Crohn’s disease (CD). However, focal myositis and isolated gastrocnemius myositis with Crohn's disease share clinical, haematological, pathological, and radiological similarities. We present a case of unilateral focal myositis of the gastrocnemius muscle in a patient with no underlying diseases, including Crohn’s disease. At clinical evaluation, we encountered a challenge in differentiating between focal myositis and the isolated gastrocnemius myositis of Crohn’s due to similarities in clinical manifestation. We attempt to clarify focal myositis and isolated gastrocnemius myositis through our case report and a review of literature.

Several techniques have been employed for deletion of the NKX3.1 gene, resulting in developmental defects of the prostate, including alterations in ductal branching morphogenesis and prostatic secretions as well as epithelial hyperplasia and dysplasia. To investigate whether the CRISPR/Cas9-mediated technique can be applied to study prostate carcinogenesis through exon I deletion of NKX3.1 gene, alterations in the prostatic intraepithelial neoplasia (PIN) and their regulatory mechanism were observed in the prostate of NKX3.1 knockout (KO) mice produced by the CRISPR/Cas9-mediated NKX3.1 mutant gene, at the ages of 16 and 24 weeks. The weight of dorsal-lateral prostate (DLP) and anterior prostate (AP) were observed to be increased in only the 24 weeks KO mice, although morphogenesis was constant in all groups. Obvious PIN 1 and 2 lesions were frequently detected in prostate of the 24 weeks KO mice, as compared with the same age wild type (WT) mice. Ki67, a key indicator for PIN, was densely stained in the epithelium of prostate in the 24 weeks KO mice, while the expression of p53 protein was suppressed in the same group. Also, both the 16 and 24 weeks KO mice reveal inhibition of the PI3K/AKT/mTOR pathway in the prostate. However, prostate specific antigen (PSA) levels and Bax/Bcl-2 expressions were decreased in the prostate of 16 weeks KO mice, and were increased in only the 24 weeks KO mice. Taken together, the results of the present study provide additional evidence that CRISPR/Cas9-mediated exon 1 deletion of the NKX3.1 gene successfully induces PIN lesions, along with significant alterations of Ki67 expression, EGFR signaling pathway, and cancer-regulated proteins.

Local fat infiltration of the thoracic cavity is a rare initial presentation of Bochdalek hernia. We report a case of Bochdalek hernia in a child with leukemia that demonstrated initial local fat infiltration of the thoracic cavity on computed tomography scan and progressed to an obvious diaphragmatic hernia on subsequent follow-up. We suggest that initial local fat infiltration of the thoracic cavity on computed tomography scan may indicate a potential diaphragmatic hernia.

Epidermal growth factor receptor mutation-positive non–small cell lung cancer is cared for mainly by target therapeutics in the clinical treatment at present. We investigated the antitumor effect of HangAmDan-B1 (HAD-B1) combined with afatinib on H1975 (L858R/T790M double mutation) lung cancer cells. The combined treatment of HAD-B1 with afatinib inhibited the proliferation of H1975 cells in a dose-dependent manner compared with the treatment of afatinib or HAD-B1 alone. The combined treatment group significantly induced early apoptosis and cell cycle arrest of the cells compared with afatinib- or HAD-B1-treated control group. Profile analysis of cell cycle proteins in H1975 cells treated with the combination of HAD-B1 and afatinib using InnoPharmaScreen antibody microarray showed downregulation of pERK1/2 and upregulation of p16 in the cells. In vivo tumor growth assay in xenograft animal model of human H1975 lung cancer cells revealed that the mean tumor volume in the group treated with the combination of HAD-B1 and afatinib showed a significant reduction compared with the control groups.

Purpose: We evaluated changes in and factors affecting second-hand smoke (SHS) exposure in a panel study of nonsmokers. Methods: This study was based on data from a larger study of tobacco use among a representative sample of adults of Korean descent residing in California. Participants included 846 males and 1,399 females who were nonsmokers at baseline (2005–2006) and at follow-up (2007–2009). Participants were selected by probability sampling and were interviewed by telephone. Results: At baseline, 50.0% were exposed to any SHS, and at follow-up 2 years later, 60.4% were exposed to any SHS (p < .001). SHS exposure at baseline was associated with acculturation, employment, spousal smoking, and having a friend who smoked (p < .001). Employment, spousal smoking, and other family members smoking were associated with SHS at follow-up (p < .001). The odds ratio of SHS in the employed group declined from 2.01 at baseline to 1.53 at follow-up, that of the group having a smoking spouse increased from 1.88 to 2.36, and that of the group having other family members smoking increased from 1.20 to 1.69. Conclusions: We showed that SHS exposure increased among Korean American nonsmokers in California, and the most important variables explaining the change in SHS exposure involved smoking among others with whom the subject is associated. These findings could be used as objective evidence for developing public health policies to reduce SHS exposure.

Background: Protease-activated receptor-2 (PAR-2)-modulated tight junctions (TJs) have been suggested to be involved in the pathogenesis of chronic inflammatory diseases. However, immunopathogenesis remains to be investigated among patients with allergic rhinitis (AR). Objective: This study sought to investigate the role of PAR-2 in the modulation of epithelial barrier function and the expression of TJs in the nasal mucosa of AR patients. Methods: The expression of TJs and PAR-2 of the nasal mucosa in AR patients and control subjects by immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. In vitro, Primary human nasal epithelial cells (pHNECs) of AR patients were stimulated by Der p1 to analyze the correlation between PAR-2 and TJs expression. Der p1-induced pHNECs were treated with the PAR-2 agonist SLIGRL-NH2 and antagonist FSLLRY-NH2. Fluorescein isothiocyanate–dextran 4 kDa detection was employed as an indicator of epithelial permeability. Results: Lower expression levels of TJs in the nasal epithelium of AR patients were observed in comparison with that in control subjects. The PAR-2 level was markedly increased following treatment with 1,000 ng/mL of Der p1 for 24 hours in a cellular model of AR. The expression of PAR-2 was increased in Der p1-induced pHNECs of AR patients and correlated inversely with zonula occlidens (ZO)-1 and claudin-1. Treatment with Der p1 further downregulated TJs expression and promoted an increased epithelial permeability in Der p1-induced pHNECs. Conclusions: PAR-2 could downregulate the expression of ZO-1 and claudin-1, which is involved in epithelial barrier dysfunction in AR. [ABSTRACT FROM AUTHOR]

Trigonella foenum-graecum (fenugreek) can ameliorate dyslipidemia, but the detailed mechanism is unclear. In this study, we examined the effects of fenugreek on hepatic lipid metabolism, particularly lipogenesis, which is enhanced in obesity and diabetes, in diabetic obese KK-Ay mice. KK-Ay mice were fed a control high-fat diet (HFD; 60% of energy as fat) (C group) or an HFD containing 0.5% or 2% fenugreek (0.5F and 2.0F groups, respectively) for 4 wk. Hepatic and plasma TG and mRNA expression levels of lipogenic genes were lower in the 2.0F group at 4 wk (P < 0.05), but not in the 0.5F group, than in the C group. The hydrolyzed saponin fraction, but not the saponin fraction per se, in fenugreek inhibited the accumulation of TG in HepG2 cells. We fractionated the hydrolyzed saponin into 15 fractions by HPLC and examined the effect of these fractions on TG accumulation in HepG2 cells. Fraction 11 inhibited TG accumulation in HepG2 cells and we determined by liquid chromatography tandem MS that the active substance contained in fraction 11 is diosgenin. Diosgenin (5 and 10 μmol/L) inhibited the accumulation of TG and the expression of lipogenic genes in HepG2 cells. Moreover, diosgenin inhibited the transactivation of liver-X-receptor-α, as measured using a luciferase assay system and by gel mobility shift assay. These findings suggest that fenugreek ameliorates dyslipidemia by decreasing the hepatic lipid content in diabetic mice and that its effect is mediated by diosgenin. Fenugreek, which contains diosgenin, may be useful for the management of diabetes-related hepatic dyslipidemias. [ABSTRACT FROM AUTHOR]

PURPOSE: To identify the health concerns for which adolescent residents in New South Wales, Australia, do not receive health care, and the associated factors, including their sociodemographic distribution. METHODS: Purposive sampling was used to recruit school students who were stratified by gender and age (12-14, 14-16 and 16-17 years), from schools stratified by socioeconomic status and urban/rural location. Out-of-school young people were recruited through youth health services. Qualitative methods were used to collect and analyze data. RESULTS: Eighty-one focus groups were conducted. Most young people defined health solely in terms of their physical well-being, but still identified a broad range of situations, conditions, or behaviors which they believed might affect their health. One-third of females and two-thirds of males said they would not seek help for their health concerns, and when they did, were most likely to seek help from family, friends, or others they trusted. When professional help was sought, young people again preferred someone they knew and trusted. The three groups of barriers to accessing health care were: concerns about confidentiality, knowledge of services and discomfort in disclosing health concerns, and accessibility and characteristics of services. Factors related to use of health care services were associated with age, gender, and location, but rarely with socioeconomic status. CONCLUSIONS: The majority of these young people in New South Wales (particularly males) do not seek health care despite identifying a broad range of issues that affect their health. [ABSTRACT FROM AUTHOR]

Background Abnormalities in mitochondrial structure or function are closely related to the development of malignant tumors. Mitochondrial metabolic reprogramming provides precursor substances and energy for the vital activities of tumor cells, so that cancer cells can rapidly adapt to the unfavorable environment of hypoxia and nutrient deficiency. Mitochondria can enable tumor cells to gain the ability to proliferate, escape immune responses, and develop drug resistance by altering constitutive junctions, oxidative phosphorylation, oxidative stress, and mitochondrial subcellular relocalization. This greatly reduces the rate of effective clinical control of tumors. Purpose Explore the major role of mitochondria in cancer, as well as targeted mitochondrial therapies and mitochondria-associated markers. Conclusions This review provides a comprehensive analysis of the various aspects of mitochondrial aberrations and addresses drugs that target mitochondrial therapy, providing a basis for clinical mitochondria-targeted anti-tumor therapy.

The effect of early growth response-1 (EGR1) on cancer invasion remains controversial depending on the cancer type. EGR1 is known to slow the progression of cancer by inhibiting the expression of MMP2. However, the effect of EGR1 on MMP9, which is important for HNSCC invasion, is disputed. Our aim is to clarify the tumor suppressor role of EGR1 in downregulating MMP9. We also consider MDM2, an enhancer of MMP9 expression. EGR1 mRNA and protein expression were compared in normal and HNSCC tissues using The Cancer Genome Atlas (TCGA) dataset analysis as well as immunohistochemistry (IHC). In vitro cell invasion was performed by two-dimension (2-D) and three-dimension (3-D) spheroids Matrigel invasion assay. TCGA data showed significantly higher EGR1 mRNA levels in nonmetastatic HNSCC tissues than in metastatic tissues. IHC analysis showed significantly higher levels of nuclear EGR1 expression in primary tumor tissues than in paired metastatic lymph node tissues. Transient EGR1 overexpression inhibited the Matrigel invasion of HNSCC cells, as well as decreasing mRNA of MMP9 and MDM2. Consistent with these observations, TCGA data analysis found significantly fewer metastatic patients among a subgroup of a large population presenting higher EGR1 expressions with lower MMP9 and/or MDM2. Our data suggests that EGR1 might be a potential candidate to attenuate HNSCC metastasis. [ABSTRACT FROM AUTHOR]

Purpose We report a dosimetric study in whole breast irradiation (WBI) of plan robustness evaluation against position error with two radiation techniques: tangential intensity-modulated radiotherapy (T-IMRT) and multi-angle IMRT (M-IMRT). Methods Ten left-sided patients underwent WBI were selected. The dosimetric characteristics, biological evaluation and plan robustness were evaluated. The plan robustness quantification was performed by calculating the dose differences (Δ) of the original plan and perturbed plans, which were recalculated by introducing a 3-, 5-, and 10-mm shift in 18 directions. Results M-IMRT showed better sparing of high-dose volume of organs at risk (OARs), but performed a larger low-dose irradiation volume of normal tissue. The greater shift worsened plan robustness. For a 10-mm perturbation, greater dose differences were observed in T-IMRT plans in nearly all directions, with higher Δ D 98% , Δ D 95% , and Δ D mean of CTV Boost and CTV. A 10-mm shift in inferior (I) direction induced CTV Boost in T-IMRT plans a 1.1 (Δ D 98% ), 1.1 (Δ D 95% ), and 1.7 (Δ D mean ) times dose differences greater than dose differences in M-IMRT plans. For CTV Boost, shifts in the right (R) and I directions generated greater dose differences in T-IMRT plans, while shifts in left (L) and superior (S) directions generated larger dose differences in M-IMRT plans. For CTV, T-IMRT plans showed higher sensitivity to a shift in the R direction. M-IMRT plans showed higher sensitivity to shifts in L, S, and I directions. For OARs, negligible dose differences were found in V 20 of the lungs and heart. Greater Δ D max of the left anterior descending artery (LAD) was seen in M-IMRT plans. Conclusion We proposed a plan robustness evaluation method to determine the beam angle against position uncertainty accompanied by optimal dose distribution and OAR sparing.

Objectives: To confirm the characteristics of gait events and muscle activity in the lower limbs of the affected and unaffected sides in patients with hemiplegia. Design: Cross-sectional study. Setting: Motion analysis laboratory of the Wonkwang University Gwangju Hospital. Participants: Outpatients, diagnosed with ischemic stroke more than 3 months and less than 9 months before participating in the study (N=29; 11 men, 18 women). Interventions: Not applicable. Main Outcome Measures: The gait event parameters and time- and frequency-domain electromyogram (EMG) parameters of the lower limbs of the affected and unaffected sides was determined using BTS motion capture with the Delsys Trigno Avanti EMG wireless system. Results: The swing time, stance phase, swing phase, single support phase, and median power frequency of the gastrocnemius muscle showed a significant difference between the affected and unaffected sides. Using a logistic regression model, the swing phase, single support phase, and median frequency of the gastrocnemius muscle were selected to classify the affected side. Conclusion: The single support phase of the affected side is shortened to reduce load bearing, which causes a reduction in the stance phase ratio. Unlike gait-event parameters, EMG data of hemiplegic stroke patients are difficult to generalize. Among them, the logistic regression model with some affected side parameters expected to be set as the severity and improvement baseline of the affected side. Additional data collection and generalization of muscle activity is required to improve the classification model.

Objectives: This study reports on the long-term effects of the Better Life After Cancer: Energy, Strength, and Support (BLESS) program, a 12-week social capital-based exercise adherence program for breast cancer survivors (BCS), implemented using a randomized controlled trial design. The study investigated outcomes related to cancer-related fatigue (CRF), quality of life (QOL), physical activity, depression, anxiety, sleep quality, and social capital. Methods: Participants who had moderate or greater CRF were randomly assigned to the intervention (n = 24), consisting of supervised and home-based exercise, or the control (n = 26), who received exercise leaflets. Generalized estimating equations models were fitted for the outcome variables. The assessment points were baseline (M1), immediately after completing the intervention at 12 weeks (M2), 1 month (M3), and 6 months post-intervention (M4). Results: A significant reduction in the total CRF score was found for both groups. We observed a significant time by group effect at M2, indicating a reduction of behavioral/severity CRF scores and a higher increase of physical activity. Also, there was an increase in the QOL score of both groups at M2, M3, and M4, compared to M1. Both groups had reduced anxiety at M3 and M4 compared to M1. The time by group effect for depression, sleep quality and social capital was not statistically significant. Conclusion: This 12-week exercise adherence program improved behavioral/severity CRF and physical activity post-intervention. Both the experimental group and control group showed significant improvements in CRF, QOL, and anxiety domains compared to the baseline, which extended to 6 months post-intervention. Trial registration: Korean Clinical Research Information Service (KCT0005763)

Human adipose-derived mesenchymal stem cells (hAMSCs) are capable of immunomodulation and regeneration after neural injury. For these reasons, hAMSCs have been investigated as a promising stem cell candidate for stroke treatment. However, noninvasive experiments studying the effects of grafted stem cells in the host brain have not yet been reported. Cerebrospinal fluid (CSF), which can be collected without sacrificing the subject, is involved in physiological control of the brain and reflects the pathophysiology of various neurological disorders of the central nervous system (CNS). Following stem cell transplantation in a stroke model, quantitative analysis of CSF proteome changes can potentially reveal the therapeutic effect of stem cells on the host CNS. We examined hAMSC-secreted proteins obtained from serum-free culture medium by liquid chromatography-tandem mass spectrometry (LC-MS/MS), which identified several extracellular matrix proteins, supporting the well-known active paracrine function of hAMSCs. Subsequently, we performed label-free quantitative proteomic analysis on CSF samples from rat stroke models intravenously injected with hAMSC (experimental) or phosphate buffered saline (control). In total, 524 proteins were identified; among them, 125 and 91 proteins were increased and decreased with hAMSC treatment, respectively. Furthermore, gene set enrichment analysis revealed three proteins, 14-3-3 theta, MAG, and neurocan, that showed significant increases in the hAMSC-treated model; these proteins are core members of neurotrophin signaling, nerve growth factor (NGF) signaling, and glycosaminoglycan metabolism, respectively. Subsequent histological and neurologic function experiments validated proliferative neurogenesis in the hAMSC-treated stroke model. We conclude that (i) intravenous injection of hAMSCs can induce neurologic recovery in a rat stroke model and (ii) CSF may reflect the therapeutic effect of hAMSCs. Additionally, proteins as 14-3-3 theta, MAG, and neurocan could be considered as potential CSF biomarkers of neuroregeneration. These CSF proteome profiling results would be utilized as valuable resource in further stroke studies.

Purpose: This study aimed to investigate the parameters with a significant impact on delivery quality assurance (DQA) failure and analyze the planning parameters as possible predictors of DQA failure for helical tomotherapy. Methods: In total, 212 patients who passed or failed DQA measurements were retrospectively included in this study. Brain (n = 43), head and neck (n = 37), spinal (n = 12), prostate (n = 36), rectal (n = 36), pelvis (n = 13), cranial spinal irradiation and a treatment field including lymph nodes (n = 24), and other types of cancer (n = 11) were selected. The correlation between DQA results and treatment planning parameters were analyzed using logistic regression analysis. Receiver operating characteristic (ROC) curves, areas under the curves (AUCs), and the Classification and Regression Tree (CART) algorithm were used to analyze treatment planning parameters as possible predictors for DQA failure. Results: The AUC for leaf open time (LOT) was 0.70, and its cut-off point was approximately 30%. The ROC curve for the predicted probability calculated when the multivariate variable model was applied showed an AUC of 0.815. We confirmed that total monitor units, total dose, and LOT were significant predictors for DQA failure using the CART. Conclusions: The probability of DQA failure was higher when the percentage of LOT below 100 ms was higher than 30%. The percentage of LOT below 100 ms should be considered in the treatment planning process. The findings from this study may assist in the prediction of DQA failure in the future.