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COVID-19 can lead to pulmonary complications, including organizing pneumonia. Steroids are essential in treating post-COVID-19 organizing pneumonia. However, research on the clinical benefits of initiating steroid treatment early for this condition is limited. To investigate the steroid initiation time in its association with treatment duration and corticosteroid dose for treating post-COVID-19 organizing pneumonia, we analyzed the data of 91 patients with post-COVID-19 organizing pneumonia at Chonnam National University Hospital between October 2020 and December 2022. Patients were categorized into early and late groups based on time from COVID-19 diagnosis to steroid initiation time for organizing pneumonia. The mean time interval between COVID-19 infection and steroid initiation time for treating organizing pneumonia, was 18.4±8.6 days. Within the early treatment group (treatment initiated <18.4 days after COVID-19), which included 55 patients, the mean duration of steroid treatment was 43.1±18.3days. In contrast, the late treatment group (initiated ≥18.4 days after COVID-19), which consisted of 36 patients, had a longer mean duration of steroid treatment 59.1±22.6 days) (p<0.01). Regarding corticosteroid dosing, the early treatment group had an average dosage of 0.5±0.3 mg/kg/day, in contrast to the late group, which averaged 0.8±0.3 mg/kg/day (p<0.01). Regression analysis showed steroid initiation time significantly influenced treatment duration (β=0.80, p<0.01) and dosage (β=0.03, p<0.01). The clinical benefits of early steroid treatment for post-COVID-19 organizing pneumonia may lie in its association with reduced steroid treatment duration and dosage. [ABSTRACT FROM AUTHOR]

Long-acting β2-agonist (LABA)/long-acting muscarinic-antagonist (LAMA) dual therapy has been found to be more effective than LAMA monotherapy in the treatment of chronic obstructive pulmonary disease (COPD). However, among patients with group B or D COPD, the characteristics of patients for whom LABA/LAMA dual therapy is superior to LAMA monotherapy in minimizing acute exacerbations remain unknown. With data from a prospective COPD cohort, subgroup analyses were conducted to determine whether LABA/LAMA dual therapy was superior to LAMA monotherapy in reducing the rate of acute exacerbations in group B and D COPD patients. Group B and D COPD patients taking LAMA or LABA/LAMA were enrolled according to the 2022 Global initiative for Chronic Obstructive Pulmonary Disease guidelines. A total of 737 patients were included in this study: 600 with group B COPD and 137 with group D COPD. Compared with patients taking LAMA monotherapy, those taking LABA/ LAMA had a significantly lower incidence of acute exacerbations over 1 year. In the subgroup of patients ≥70 years old, there was a significantly lower risk of severe COPD exacerbations among group B patients taking LABA/LAMA than among those taking LAMA monotherapy (odds ratio [OR], 0.258; 95% confidence interval [CI], 0.095– 0.703). In contrast, in the subgroup of group D patients with COPD Assessment Test scores ≥25, compared with LAMA monotherapy, LABA/LAMA treatment was associated with lower risk of severe COPD exacerbations (OR, 0.115; 95% CI, 0.018-0.749). The combination of LABA and LAMA was found to be superior to LAMA monotherapy, especially for treating older adults with group B COPD, as well as for group D patients with severe symptoms. [ABSTRACT FROM AUTHOR]

Background: Disorders of consciousness (DOC) resulting from acquired brain injury (ABI) increase the mortality rate of patients, complicate rehabilitation, and increase the physical and economic burden that DOC imposes on patients and their families. Thus, treatment to promote early awakening from DOC is vital. Transcranial direct current stimulation (tDCS) has shown great potential for promoting neuro-electrochemical activity. However, previous tDCS studies did not consider structural damage or head and brain lesions, so the applicability of the results to all DOC patients was limited. In this study, to establish a patientspecific tDCS treatment plan considering the brain lesions of and damage sustained by DOC patients, we considered the electric field calculated by a the "finite electric" three-dimensional brain model based on magnetic resonance images. This protocol was developed to aid tDCS treatment of actual patients, and to verify its safety and effectiveness. Methods/design: Twenty-four patients with DOC after ABI will be enrolled in this cross-over trial. All participants will receive typical rehabilitation combined with sham tDCS and typical rehabilitation plus personalized tDCS (P-tDCS). Each interventional period will last 2 weeks (30 min/day, 5 days/week). The primary outcome [score on the Korean version of the Coma Recovery Scale-Revised (K-CRS-R)] will be assessed at baseline and the end of the first day of the intervention. Secondary outcomes (K-CRS-R at 1 week and 2 weeks after experimental session and quantitative EEG changes quantitative electroencephalography changes) will be measured at baseline and the end of week 4. Adverse events will be recorded during each treatment session. Discussion: For patients with neurological disorders, tDCS has served as a painless, non-invasive, easily applied, and effective therapy for several decades, and there is some evidence that it can improve the level of consciousness of patients with DOC. However, variability in the effects on consciousness among subjects have been reported and personalized strategies are lacking. This protocol is for a randomized controlled trial designed to validate the effectiveness and safety of P-tDCS combined with typical rehabilitation for DOC. [ABSTRACT FROM AUTHOR]

Background/Aim: Renal-type clear cell carcinoma (RTCCC) occurring as a primary tumor in an extra-renal location, especially in the prostate, is very rare. In this report, we present a rare case of RTCCC of the prostate and review the current literature on this condition. Case Report: The patient was a 76-year-old man who presented with urinary symptoms. Cystoscopic findings showed tumor-like lesions in the dome, neck, and anterior wall of the urinary bladder. Biopsy revealed clear cell carcinoma (CCC). Transrectal needle biopsy of the prostate revealed prostatic adenocarcinoma with CCC features. Immunohistochemically, tumor cells of the bladder and prostate were compatible with prostatic carcinoma. The whole-body radiologic workup did not reveal any renal or other organ malignancies. Transurethral resection of the prostate and bladder tumor was performed. The patient underwent regular follow-up cystoscopic examination and urine cytology. No recurrence was observed 19 months after the diagnosis. Conclusion: This was a case of RTCCC arising in the prostate. RTCCC of the prostate is extremely rare and shows very similar histological and immunohistochemical features to those of CCC occurring in the kidney. Pathologists should be aware of such an entity whenever they see clear cells in urinary tract malignancies. [ABSTRACT FROM AUTHOR]

Background: Inflammatory myofibroblastic tumor (IMT) is a rare type of soft-tissue neoplasm. IMT of the urinary tract is more common in the bladder and kidneys. Prostatic IMT is extremely rare. Case Report: We present a rare case of IMT of the prostate and a literature review on this condition. The patient was a 72-year-old man who presented with urinary symptoms. Transrectal needle biopsy of the prostate revealed prostatic adenocarcinoma with nodular hyperplasia. Radical prostatectomy revealed IMT without residual adenocarcinoma. On immunohistochemical examination, the tumor cells showed positive immunoreactivity for α-smooth muscle actin, CD10, CD34, and desmin but negative immunoreactivities for anaplastic lymphoma kinase (ALK), receptor tyrosine kinase (c-KIT), and S-100 protein. The patient underwent regular follow-up examination. No recurrence was observed 4 months after the diagnosis. Conclusion: This was a case of IMT arising in the prostate. Pathologists should be aware of such an entity whenever they see spindle-cell lesions in the transrectal needle biopsy of the prostate. [ABSTRACT FROM AUTHOR]

Background/Aim: Cyclin-dependent kinase 8 (CDK8) is known to play an important role in the early development and progression of various cancers, and the Wnt/β-catenin pathway is also involved in cancer progression. Nevertheless, relatively little is known about the regulatory mechanisms of the β-catenin pathway in hepatocellular carcinoma (HCC). Materials and Methods: The complete clinicopathological features of 122 pairs of HCC and adjacent non-tumor tissues were analyzed and immunohistochemistry was used to detect the aberrant expression of CDK8 and β-catenin. Overall survival rates (OSRs) were evaluated using the Kaplan-Meier method and Cox multivariate analysis was used to assess the prognostic values. Results: Aberrant expression of nuclear β-catenin and CDK8 are independent prognostic variables that negatively affect the OSR. The aberrant expression of CDK8 was associated with the dysregulated expression of β-catenin and correlated with a poor prognosis. Conclusion: Inhibition of CDK8 and/or nuclear β-catenin expression pattern could serve as a promising therapeutic strategy for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of particulate dentin-plaster of Paris with and without platelet-rich plasma (PRP) on bone healing and new bone formation around titanium dental implants in a canine model. Histologic sections and histomorphometric analysis of the defects were obtained at 6 and 12 weeks after surgery. Materials and Methods: Three circular bone defects were surgically prepared in iliac crest sites in each of 10 animals. A total of 30 Avana dental implants were placed in the animals. They were self-tapping, screw-type implants, 10 mm in length and 4 mm in diameter, all made of commercially pure titanium. A titanium implant was placed centrally in each defect. In each dog, the defects were treated with 1 of the following 3 treatment modalities: (1) no treatment (control); (2) grafting with particulate dentin-plaster of Paris; (3) grafting with particulate dentin-plaster of Paris and PRP. Results: Histologic analysis showed that all of the bone defects surrounding the implants that were treated with particulate dentin-plaster of Paris, with and without PRP, were filled with new bone. The defects that were not treated (control) demonstrated new bone formation only in the inferior threaded portion of the implants. Discussion: Histomorphometric results revealed a higher percentage of bone contact with particulate dentin-plaster of Paris and PRP compared to the control and particulate dentin-plaster of Paris. Conclusions: These results suggested that bone defects around titanium implants can be treated successfully with particulate dentin-plaster of Paris, and that the outcome can be improved if PRP is also used. [ABSTRACT FROM AUTHOR]

The guidelines for chronic obstructive pulmonary disease (COPD) treatment are important for the management of the disease. However, studies regarding the treatment adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines have been scarce in Korea. Therefore, to examine the adherence to the GOLD guidelines, we examined the patterns of prescribed medication in COPD patients from 2011 to 2018. Patients were classified as having been appropriately and inappropriately treated (overtreatment or undertreatment) for the GOLD group. Appropriate medical therapy was defined as using the first choice or alternative choice drug recommended in the GOLD guidelines. Inappropriate therapy was classified as overtreatment or undertreatment in accordance with the categorization in the GOLD guidelines. According to treatment of 2011 GOLD guidelines, there was inappropriate treatment in 52.3% in group A, 47.3% in group B, 56.3% in group C, and 17.8% in group D. According to treatment of 2017 GOLD guidelines, there was inappropriate treatment in 66.7% in group A, 45.3% in group B, 14.3% in group C, and 24.0% in group D. The common type of inappropriate COPD treatment is overtreatment, with inhaled corticosteroid (ICS) containing regimens. In conclusions, adherence to the GOLD guideline by the pulmonologist in clinical practice is still low in Korea. Therefore, we need better strategies to both optimize the use of the guidelines and adhere to the guidelines as well. [ABSTRACT FROM AUTHOR]

Intramuscular angiomyolipoma (AML) is a rare, benign hamartomatous lesion, that typically occurs in the kidney. Extrarenal AMLs are extremely rare and have been commonly described in the liver, spleen, and reproductive system. We report a case of AML of the upper arm and a review of the literature on this condition. The patient was a 34-year-old man who presented with a palpable mass that was in his left upper arm for 4 years. Histopathologic evaluation demonstrated a hamartomatous lesion consisting of a mixture of thin and thick blood vessels, mature adipose tissue, and smooth muscle bundles in the triceps brachii muscle. Immunohistochemically, tumor cells showed negative immunoreactivity for HMB45. These findings were consistent with an extrarenal AML. This was the second reported case of intramuscular AML arising in the extremities. Pathologists should be aware of such an entity whenever they see extrarenal vascular hamartomas not associated with tuberous sclerosis and HMB45 positivity. [ABSTRACT FROM AUTHOR]

Limbic encephalitis (LE) is characterized by short-term memory loss, disorientation, agitation, seizures, and histopathological evidence of medial temporal lobe inflammation. Leucine-rich, glioma inactivated 1 (LGI-1) is an auto-antigen associated with LE. We report a 37-year-old male patient with LGI-1-related LE who presented with recurrent episodes of selective amnesia, seizure-like activity, confusion, and personality change. His symptoms were significantly improved with steroid therapy. Thorough differential diagnosis with consideration for autoimmune encephalitis should be in patients with presentation of symptoms, such as memory impairment, personality change and seizure-like activity, especially when other neurological diagnoses are excluded. [ABSTRACT FROM AUTHOR]

Objective: Deep brain stimulation (DBS) of the centromedian thalamic nucleus (CM) can be an alternative treatment option for intractable epilepsy patients. Since CM may be involved in widespread cortico-subcortical networks, identification of the cortical sub-networks specific to the target stimuli may provide further understanding on the underlying mechanisms of CM DBS. Several brain structures have distinguishing brain connections that may be related to the pivotal propagation and subsequent clinical effect of DBS. Methods: To explore core structures and their connections relevant to CM DBS, we applied electroencephalogram (EEG) and diffusion tensor imaging (DTI) to 10 medically intractable patients - three generalized epilepsy (GE) and seven multifocal epilepsy (MFE) patients unsuitable for resective surgery. Spatiotemporal activation pattern was mapped from scalp EEG by delivering low-frequency stimuli (5 Hz). Structural connections between the CM and the cortical activation spots were assessed using DTI. Results: We confirmed an average 72% seizure reduction after CM DBS and its clinical efficiency remained consistent during the observation period (mean 21 months). EEG data revealed sequential source propagation from the anterior cingulate, followed by the frontotemporal regions bilaterally. In addition, maximal activation was found in the left cingulate gyrus and the right medial frontal cortex during the right and left CM stimulation, respectively. From DTI data, we confirmed concrete structural connections between CM and those maximal activation spots identified from EEG data. Conclusion: These results suggest that the anterior cingulate can be a core cortical structure for the bilateral propagation of CM stimulation. Our DTI findings also indicate that the propagation of CM stimulation may rely upon integrity of structural connections between CM and these key cortical regions. Structures and their connections found in this study may be relevant in the interpretation of the clinical outcomes of CM DBS. [ABSTRACT FROM AUTHOR]

MDL-12330A is a widely used adenylyl cyclase (AC) inhibitor that blocks AC/cAMP signaling. In this study, we demonstrated a novel antitumor activity of this drug in gastric carcinoma (GC) cell lines. In these GC cells, MDL-12330A reduced cell viability and induced cell death in a concentration-dependent manner. At a moderate concentration (∼20 μM), MDL-12330A mainly induced apoptotic death whereas at concentrations greater than 20 μM, it increased non-apoptotic cell death. The induction of apoptosis was at least partially regulated by CHOP-mediated DR5 upregulation, as detected by immunoblotting and gene interference assays. More importantly, low concentrations of MDL-12330A effectively enhanced recombinant human tumor necrosis factor (TNF)-related apoptosis-inducing ligand (rhTRAIL)- induced apoptosis and clonogenicity in these gastric cancer cells. This study demonstrates a possible role of MDL-12330A as a potential sensitizer to TRAIL, and suggests a novel therapeutic strategy targeting gastric cancer cells. [ABSTRACT FROM AUTHOR]

Andrographolide, a natural compound isolated from Andrographis paniculata, has been reported to possess antitumor activity. In the present study, the effect of andrographolide in human gastric cancer (GC) cells was investigated. Andrographolide induced cell death with apoptotic and non-apoptotic features. At a low concentration, andrographolide potentiated apoptosis and reduction of clonogenicity triggered by recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL). Exposure of GC cells to andrographolide altered the expression level of several growth-inhibiting and apoptosis-regulating proteins, including death receptors. It was demonstrated that activity of the TRAIL-R2 (DR5) pathway was critical in the development of andrographolide-mediated rhTRAIL sensitization, since its inhibition significantly reduced the extent of apoptosis induced by the combination of rhTRAIL and andrographolide. In addition, andrographolide increased reactive oxygen species (ROS) generation in a dose-dependent manner. N-acetyl cysteine prevented andrographolide-mediated DR5 induction and the apoptotic effect induced by the combination of rhTRAIL and andrographolide. Collectively, the present study demonstrated that andrographolide enhances TRAIL-induced apoptosis through induction of DR5 expression. This effect appears to involve ROS generation in GCs. [ABSTRACT FROM AUTHOR]

Background: Scedosporium apiospermum, which can usually be isolated from soil, polluted stream water and decaying vegetation, is increasingly recognized as an opportunistic dematiaceous fungus. The mortality rate of infection in immunocompromised hosts is over 50%. S. apiospermum is commonly responsible for dermal and epidermal infections (i.e., mycetoma) after traumatic penetration.Case Presentation: A 73-year-old woman was admitted to our hospital complaining of painful swelling and tenderness on the dorsum of the proximal left wrist and hand. The symptoms had persisted for approximately 2 months. A physical examination revealed a 4 x 3 cm, poorly defined, erythematous papule, which was fluctuant, with pustules and crusts on the dorsum of the left hand.Conclusions: We report a very rare case of tenosynovitis caused by S. apiospermum infection. We identified the infectious agent via molecular DNA sequencing. The infectious agent was initially misidentified as an Alternaria species by microscopic examination with lactophenol cotton blue (LPCB) staining. The infection was successfully treated with debridement and adjuvant fluconazole therapy. [ABSTRACT FROM AUTHOR]

LPIN1 is a protein that exhibits dual functions as a phosphatidic acid phosphatase enzyme in regulation of triglyceride and glycerophospholipid metabolism and a transcriptional coregulator. Through unknown tumour-promoting mechanism, LPIN1 frequently observed in various human cancer cell lines controls main cellular processes involved in cancer progression. Here, we demonstrate that LPIN1 enhances the tumour-promoting function of insulin receptor substrate 1 (IRS1) by controlling IRS1 stability. LPIN1 interacts with IRS1 in an insulin growth factor-1-dependent signalling pathway and inhibits its serine phosphorylation, and thereby eliminating ubiquitin-dependent degradation of IRS1 via proteasomal and lysosomal pathways. Consequently, LPIN1 overexpression increases IRS1 abundance and enhances IRS1's ability to induce epithelial cell proliferation and mammary tumourigenesis. By contrast, depletion or inhibition of LPIN1 in breast cancer cells leads to a decreased IRS1 level, which subsequently inhibits the RAF1-mediated signalling pathway and AP-1 activity. In the syngeneic 4T1 breast cancer model, LPIN1 overexpression increased tumour development, whereas inhibition of LPIN1 and IRS1 suppressed it. Consistent with these observations, LPIN1 levels were positively correlated with IRS1 expression in human breast cancer. Thus, our results indicate a mechanism by which IRS1 expression is increased in breast cancer, and LPIN1 may be a promising drug target for anticancer therapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the evolution of nonlesional temporal lobe epilepsy (TLE-NL) in patients treated exclusively with antiepileptic drugs and to elucidate clinical phenotypes related to the prognosis of these patients. Methods: Clinical, radiological, and electroencephalographic (EEG) findings in 84 patients with TLE-NL were reviewed. A good response group (GRG) and a poor response group (PRG) were defined if the duration of their seizure-free period was >1 year, or <1 year, respectively. Results: There were 46 (54.8%) patients in the GRG and 38 (45.2%) patients in the PRG. The number of antiepileptic drugs administered was significantly lower in the GRG than that in the PRG (1.3±0.8 vs 2.8±1.0, respectively; P<0.05). The GRG had a significantly older age of onset than the PRG and a lower occurrence of initial precipitating events, such as febrile seizures, central nervous system infection, and head trauma (P<0.05). The prevalence of EEG abnormality, presence of aura, generalized seizures, and automatism was less frequently observed in the GRG (P<0.05). Multivariate analysis showed that the presence of automatism and initial precipitating events were significantly associated with a poor prognosis (P<0.05). Conclusion: In contrast to the commonly assumed intractability of TLE, we found that more than 54% of patients with TLE-NL achieved a long seizure-free period. Older age at onset of TLE-NL was associated with a better prognosis. However, the presence of automatism and initial precipitating events were related to a poor prognosis. Future prospective studies with a much larger population are warranted. [ABSTRACT FROM AUTHOR]

p16 and Ki-67 immunohistochemistry can be used as an ancillary method for the diagnosis of squamous intraepithelial lesion (SIL) versus atrophic change and atypical squamous metaplasia. The aim of the present study was to evaluate the efficacy of these two immunohistochemical markers in the accurate interpretation of cervical biopsies and correlate this data with human papilloma virus (HPV) infection status. The study included 103 formalin-fixed cervical punch and cone biopsy samples, with corresponding HPV DNA test data. Histopathological staining with hematoxylin and eosin, and immunohistochemical staining for p16 and Ki-67 were reviewed by two pathologists. The positivity of p16 and Ki-67 increased significantly with the severity of the cervical lesion in patients with a high-risk-HPV (HR-HPV) infection status (P<0.001). However, there was discordance in the HPV-negative group. Furthermore, concomitant diffuse, strong and block positive staining of p16, and a high Ki-67 index were implicated in high-grade SIL in the HR-HPV group. Thus, the two markers were efficient in advancing the diagnostic accuracy of cervical biopsies in the HR-HPV group; however, application of immunohistochemical results should be carefully considered in the HPV-negative group. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease is associated with metabolic syndrome and has the unique characteristic of excess lipid accumulation in liver. G-protein-coupled receptor 119 (GPR119) is a promising target for type 2 diabetes. However, the role of GPR119 activation in hepatic steatosis and its precise mechanism has not been investigated. In primary cultured hepatocytes from wild-type and GPR119 knockout (KO) mice, expression of lipogenic enzymes was elevated in GPR119 KO hepatocytes. Treatment of hepatocytes and HepG2 cells with GPR119 agonists in phase 2 clinical trials (MBX-2982 [MBX] and GSK1292263) inhibited protein expression of both nuclear and total sterol regulatory element binding protein (SREBP)-1, a key lipogenesis transcription factor. Oral administration of MBX in mice fed a high-fat diet potently inhibited hepatic lipid accumulation and expression levels of SREBP-1 and lipogenesis-related genes, whereas the hepatic antilipogenesis effects of MBX were abolished in GPR119 KO mice. MBX activated AMPK and increased Ser-372 phosphorylation of SREBP-1c, an inhibitory form of SREBP-1c. Moreover, inhibition of AMPK recovered MBX-induced down-regulation of SREBP-1. These findings demonstrate for the first time that the GPR119 ligand alleviates hepatic steatosis by inhibiting SREBP-1-mediated lipogenesis in hepatocytes.--Yang, J. W., Kim, H. S., Im, J. H., Kim, J. W., Jun, D. W., Lim, S. C., Lee, K., Choi, J. M., Kim, S. K., Kang, K. W. GPR119: a promising target for nonalcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

The incidence rate of cervical cancer in Korea is still higher than in other developed countries, notwithstanding the national mass-screening program. Furthermore, a new method has been introduced in cervical cancer screening. Therefore, the committee for cervical cancer screening in Korea updated the recommendation statement established in 2002. The new version of the guideline was developed by the committee using evidence-based methods. The committee reviewed the evidence for the benefits and harms of the Papanicolaou test, liquid-based cytology, and human papillomavirus (HPV) testing, and reached conclusions after deliberation. The committee recommends screening for cervical cancer with cytology (Papanicolaou test or liquid-based cytology) every three years in women older than 20 years of age (recommendation A). The cervical cytology combined with HPV test is optionally recommended after taking into consideration individual risk or preference (recommendation C). The current evidence for primary HPV screening is insufficient to assess the benefits and harms of cervical cancer screening (recommendation I). Cervical cancer screening can be terminated at the age of 74 years if more than three consecutive negative cytology reports have been confirmed within 10 years (recommendation D). [ABSTRACT FROM AUTHOR]

Motivational interviewing is a directive, collaborative conversation style for strengthening a person's own motivation and commitment to change. Motivational interviewing provides diabetes educators with appropriate tools to interview patients with diabetes who are resistant to change and can help with lifestyle change and health behavior. Motivational interviewing has been incorporated into health care settings to treat a variety of health conditions. The purpose of this article is to provide diabetes educators with ways to actually use motivational interviewing in diabetes self-management education. [ABSTRACT FROM AUTHOR]

The antiseizure efficacy and safety of levetiracetam (LEV) is well documented; however, few clinical studies have investigated the predictability of patient responsiveness to LEV, especially when the drug is first administered. The aim of this study was to ascertain the utility of clinical, electrophysiological, and neuroimaging parameters for assessing the early response to LEV treatment in focal epilepsy patients. Twelve confirmed focal epilepsy patients were included who had never taken LEV before. At baseline and 1 month after LEV administration, all subjects underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and electroencephalography (EEG), and completed the Quality of Life in Epilepsy questionnaire (QOLIE-31). Participants were divided by drug response: good versus poor. The good response group (seven subjects) was defined by a >50% decrease in seizure frequency compared to baseline (3 months before LEV intake). The other five participants with a >50% decrease in seizure frequency were placed into the poor response group. We compared the differential changes in brain glucose metabolism on FDG-PET, power spectrum on the EEG, and QOLIE-31 results between the two groups after a 1-month LEV trial. In the good response group, it was possible to identify brain regions with increased glucose metabolism, including the bilateral caudate nuclei and both frontal and left parietal regions (uncorrected P<0.005). In the poor response group, FDG-PET did not reveal any areas with significantly increased glucose metabolism. In the good response group, spectral EEG analysis revealed decreased delta power (1-3 Hz, P<0.05) in the parietal region and increased beta1 power (13-19 Hz, P<0.05) in the frontal region, whereas no significant changes were observed in the poor response group. There were no significant changes on the QOLIE-31 in either group after a 1-month LEV trial. Our results suggest that LEV-induced glucose metabolism and EEG spectral changes may be indicative of initial drug responsiveness as early as 1 month following treatment initiation. These parameters may be useful prognostic markers of antiseizure effects caused by LEV medication or may indicate an epiphenomenon of LEV-induced changes in glucose metabolism and EEG frequency. Further studies with larger sample sizes are warranted. [ABSTRACT FROM AUTHOR]

Mindfulness meditation is effective in stress management and diabetes self-care. This paper provides an overview of mindfulness meditation, the mindfulness-based stress reduction (MBSR) program, and the mindfulness-based therapy's effectiveness in diabetes self-care. Mindfulness meditation and the mindfulness-based therapy may be a useful intervention in helping diabetic patients improve stress management, emotional regulation, mental health, and overall health. Diabetes educators should have continuous interest in mindfulness meditation and will need to try to apply in diabetes self-care. [ABSTRACT FROM AUTHOR]

Pin1, a conserved enkaryotic peptidyl-prolyl cis/trans isomerase, has profound effects on numerous key-signaling molecules, and its deregulation contributes to disease, particularly cancer. Although Pin1-mediated prolyl isomerization of protein servers as a regulatory switch in signaling pathways, the significance of proline isomerase activity in chromatin modifying complex remains unclear. Here, we identify Pinl as a key negative regulator for suppressor of variegation 3-9 homologue 1 (SUV39H1) stability, a major methyltransferase responsible for histone H3 trimethyla-tion on Lys9 (H3K9me3). Pin1 interacts with SUV39H1 in a phosphorylation-dependent manner and promotes ubiq-uitraation-mediated degradation of SUV39H1. Conse-quendy, Pinl reduces SUV39H1 abundance and suppresses SUV39H1 ability to induce H3K9me3. In contrast, depletion of Pin1 in cancer cells leads to elevated STJV39H1 expression, which subsequendy increases H3K9me3, inhibiting tumorigenecity of cancer cells, hi a xenograft model with 4T1 metastatic mouse breast carcinoma cells, Pinl overexpression increases tumor growth, whereas SUV39H1 overexpression abrogates it. In human breast cancer patients, immunohistochemical staining shows mat Pin1 levels are negatively correlated with SUV39H1 as well as H3K9me3 levels. Thus, Pin1-mediated reduction of SUV39H1 stability contributes to convey oncogenic signals for aggressiveness of human breast cancer, suggesting that Pin1 may be a promising drug target for anticancer therapy. [ABSTRACT FROM AUTHOR]

Background: The GOLD 2011 document proposed a new classification system for COPD combining symptom assessment by COPD assessment test (CAT) or modified Medical Research Council (mMRC) dyspnea scores, and exacerbation risk. We postulated that classification of COPD would be different by the symptom scale; CAT vs mMRC. Methods: Outpatients with COPD were enrolled from January to June in 2012. The patients were categorized into A, B, C, and D according to the GOLD 2011; patients were categorized twice with mMRC and CAT score for symptom assessment, respectively. Additionally, correlations between mMRC scores and each item of CAT scores were analyzed. Results: Classification of 257 patients using the CAT score vs mMRC scale was as follows. By using CAT score, 60 (23.3%) patients were assigned to group A, 55 (21.4%) to group B, 21 (8.2%) to group C, and 121 (47.1%) to group D. On the basis of the mMRC scale, 97 (37.7%) patients were assigned to group A, 18 (7.0%) to group B, 62 (24.1%) to group C, and 80 (31.1%) to group D. The kappa of agreement for the GOLD groups classified by CAT and mMRC was 0.510. The mMRC score displayed a wide range of correlation with each CAT item (r = 0.290 for sputum item to r = 0.731 for dyspnea item, p < 0.001). Conclusions: The classification of COPD produced by the mMRC or CAT score was not identical. Care should be taken when stratifying COPD patients with one symptom scale versus another according to the GOLD 2011 document. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the differences in clinical characteristics and treatment outcomes between older and younger tuberculosis (TB) patients in Korea. Methods: We retrospectively analyzed the medical records of 271 younger (20-64 years old at diagnosis) and 199 older (=65 years) TB patients who had been newly diagnosed and treated at Chonnam National University Hospital from May 2008 to August 2010. Results: Dyspnea and comorbid medical conditions were more frequent and positive TB culture rates were higher in older TB patients. In chest computed tomography (CT) scans of pulmonary TB patients, older patients were less likely to have micronodules (<7 mm in diameter), nodules (<30 mm in diameter), masses (>30 mm in diameter), and cavities compared with younger patients, but were more likely to have consolidations. Incidence of adverse drug reactions did not differ between the two groups, except for severe gastrointestinal disorders. There were no significant differences in favorable treatment outcomes between younger and older TB patients (97% vs. 94%, respectively; p = 0.251). Conclusions: Older TB patients had more frequent dyspnea and less frequent active TB findings on chest CT. Treatment success and adverse drug reaction rates were similar in older and younger TB patients. [ABSTRACT FROM AUTHOR]

Background: Necrosis, a type of cell death accompanied by the rupture of the plasma membrane, promotes tumor progression and aggressiveness by releasing the pro-inflammatory and angiogenic cytokine high mobility group box 1. It is commonly found in the core region of solid tumors due to hypoxia and glucose depletion (GD) resulting from insufficient vascularization. Thus, metabolic stress-induced necrosis has important clinical implications for tumor development; however, its regulatory mechanisms have been poorly investigated. Methodology/Principal Findings: Here, we show that the transcription factor Snail, a key regulator of epithelialmesenchymal transition, is induced in a reactive oxygen species (ROS)-dependent manner in both two-dimensional culture of cancer cells, including A549, HepG2, and MDA-MB-231, in response to GD and the inner regions of a multicellular tumor spheroid system, an in vitro model of solid tumors and of human tumors. Snail short hairpin (sh) RNA inhibited metabolic stress-induced necrosis in two-dimensional cell culture and in multicellular tumor spheroid system. Snail shRNA-mediated necrosis inhibition appeared to be linked to its ability to suppress metabolic stress-induced mitochondrial ROS production, loss of mitochondrial membrane potential, and mitochondrial permeability transition, which are the primary events that trigger necrosis. Conclusions/Significance: Taken together, our findings demonstrate that Snail is implicated in metabolic stress-induced necrosis, providing a new function for Snail in tumor progression. [ABSTRACT FROM AUTHOR]

We assessed the clinical usefulness of immunohistochemical staining on skin biopsy specimens for the diagnosis of scrub typhus compared with indirect immunofluorescent antibody assay (IFA), the definitive diagnostic method for scrub typhus, in a prospective study of 125 patients with possible scrub typhus in 2005 and 2006. Skin biopsy specimens were obtained from 63 patients. To minimize the effects caused by antibiotics on immunohistochemical results, 46 patients were assessed before antibiotic administration (4 patients received antibiotic therapy before admission; 13 underwent skin biopsy after antibiotic administration at our hospital). Compared with IFA results, immunohistochemical results on maculopapular skin lesions demonstrated a sensitivity of 0.65 and a specificity of 1. Immunohistochemical results on eschars demonstrated a sensitivity of 1 and a specificity of 1. For immunohistochemical staining performed on skin lesions within 3 or 4 days of administration of antibiotics that are effective for Rickettsia, the antibiotics did not greatly influence diagnostic sensitivity. Immunohistochemical staining of skin biopsy specimens, particularly that of eschars, is sensitive and specific, and this technique can be reliable for confirming the diagnosis of scrub typhus. [ABSTRACT FROM AUTHOR]

Sopungyangjae-Tang (SYT) is a traditional Korean decoction used for the treatment of dermatitis. The aim of this study was to confirm whether or not SYT has a preventive effect on the development of atopic dermatitis in dinitrochlorobenzene-applied Nc/Nga mice. SYT was administered orally to Nc/Nga mice, which led to the remarkable suppression of the development of dermatitis, as determined by a histological examination and the serum IgE levels. Moreover, SYT inhibited the production of thymus- and activation-regulated chemokine (TARC) and its mRNA expression in a keratinocyte cell line, HaCaT, which had been stimulated with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Activation of the nuclear factor-κB (NF-κB) or activator protein-1 (AP-1) is one of the key steps in the signaling pathways mediating induction of TARC. In this study, SYT selectively suppressed NF-κB activation, which may be essential for TARC expression in TNF-α/IFN-γ treated keratinocytes. The inhibitory effect of SYT on NF-κB activation and TARC production might be associated with the anti-dermatitic effects of SYT. [ABSTRACT FROM AUTHOR]

A liposarcoma is the most frequent soft tissue sarcoma found in adults, however, a liposarcoma arising in uterus is extremely rare. Indeed, a liposarcoma coexistent with a leiomyoma is even rarer and there is only one case has been reported in the English literature to date. We describe a case of the uterine liposarcoma arising in a leiomyoma in 48-year-old woman who presented with dysmenorrhea, brownish vaginal discharge, and a rapidly enlarging lower abdominal mass. The tumor emerged from the lower segment of the endometrium and filled the endometrial cavity as a polypoid lesion. The authors of this study documented the adipocyte origin of the tumor with immunohistochemical and electron microscopical studies, the available literature was reviewed and the possible histogenesis was discussed. We herein report a case of very rare primary liposarcoma arising in a submucosal uterine leiomyoma. [ABSTRACT FROM AUTHOR]

Primary or acquired resistance of tumours to established chemotherapeutic regimens is a major concern in oncology. Attempts to improve the survival of cancer patients largely depend on strategies to prevent tumour cell resistance. 5-Fluorouracil (5-FU)-based chemotherapy with a combination of other drugs such as irinotecan (IRT) and oxaliplatin (OXT) has been reported to be effective, even though an optimal regimen has yet to be defined due to the relatively high toxicity of the procedure. The aim of this study was to examine the effect of betulinic acid (BetA) as a chemosensitizer for anticancer drug treatment in chemoresistant colon cancer cell lines. A chemoresistant cell line to 5-fluorouracil (SNU-C5/5FU-R), irinotecan (SNU-C5/IRT-R) and oxaliplatin (SNU-C5/OXT-R) treatment were derived from the wild-type colon adenocarcinoma cell line (SNU-C5/WT). The effect of BetA or a combination of anticancer drugs and BetA on the multidrug resistance-related genes, caspases, Bcl-2, Bad and cell death in the SNU-C5/WT and SNU-C5/R cell lines was analysed. BetA alone was an effective chemotherapeutic drug for the SNU-C5/WT, SNU-C5/5FU-R and SNU-C5/OXT-R cells. The combination of BetA with IRT or OXT was effective against SNU-C5/5FU-R cells, and the combination of BetA with 5-fluorouracil, IRT or OXT was effective against SNU-C5/OXT-R cells. BetA induced cancer cell death by apoptosis through the mitochondrial pathway. These findings indicate that the use of BetA as a chemosensitizer may be a new strategy to enhance the efficacy of chemotherapy. However, further studies will be needed for confirmation. [ABSTRACT FROM AUTHOR]

Cells typically die by either apoptosis or necrosis. However, the consequences of apoptosis and necrosis are quite different for a whole organism. In the case of apoptosis, the cell content remains packed in the apoptotic bodies that are removed by marcrophages, and thereby inflammation does not occur; during necrosis, the cell membrane is ruptured, and the cytosolic constituents are released into the extracellular space provoking inflammation. Recently, inflammation and necrosis have been suggested to promote tumor growth. We investigated the molecular mechanism underlying cell death in response to glucose depletion (GD), a common characteristic of the tumor microenvironment. GD induced necrosis through production of reactive oxygen species (ROS) in A549 lung carcinoma cells. Inhibition of ROS production by N-acetyl-L-cysteine and catalase prevented necrosis and switched the cell death mode to apoptosis that depends on mitochondrial death pathway involving caspase-9 and caspase-3 activation, indicating a critical role of ROS in determination of GD-induced cell death mode. We demonstrate that protein kinase C-dependent extracellular regulated kinase 1/2 (ERK1/2) activation also switched GD-induced necrosis to apoptosis through inhibition of ROS production possibly by inducing manganese superoxide dismutase (SOD) expression and by preventing GD-induced degradation of cupper zinc SOD. Thus, these results suggest that GD-induced cell death mode is determined by the protein kinase C/ERK1/2 signal pathway that regulates MnSOD and CuZnSOD and that these antioxidants may exert their known tumor suppressive activities by inducing necrosis-to-apoptosis switch. J. Cell. Physiol. 211: 371–385, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]