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Abstract Purpose The incidence of depression and anxiety is higher in patients with breast cancer than in the general population. We evaluated the degree of depression and anxiety and investigated the changes in patients with breast cancer during the treatment period and short-term follow-up period. Methods Overall, 137 patients with breast cancer were evaluated using the Patient Health Questionnaire 9-item depression scale (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7). The scales were developed as a web-based electronic patient-reported outcome measure, and serial results were assessed before the operation, after the operation, in the post-treatment period, and in the 6-month follow-up period after surgery. Results The degree of depression and anxiety increased during treatment and decreased at 6-month follow-up, even if there were no statistical differences among the four periods (PHQ-9: p = 0.128; GAD-7: p = 0.786). However, daily fatigue (PHQ-9 Q4) and insomnia (PHQ-9 Q3) were the most serious problems encountered during treatment and at 6-month follow-up, respectively. In the GAD-7, worrying too much (Q3) consistently showed the highest scores during the treatment and follow-up periods. Of the patients, 7 (5.11%) and 11 (8.03%) patients had a worsened state of depression and anxiety, respectively, after treatment compared with before treatment. Conclusion Most factors associated with depression and anxiety improved after treatment. However, factors such as insomnia and worrying too much still disturbed patients with breast cancer, even at 6-month follow-up. Therefore, serial assessment of depression and anxiety is necessary for such patients.

Abstract Cerebrovascular pathology at the biochemical level has been informed by the study of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a vascular disorder caused by NOTCH3 mutations. Previous work in CADASIL described N-terminal proteolysis of NOTCH3 generated by specific non-enzymatic cleavage of the first Asp-Pro sequence of the protein. Here, we investigated whether the second Asp-Pro peptide bond (residues 121–122) of NOTCH3 is cleaved in CADASIL. Monospecific antibodies were generated that recognize the neo-epitope predicted to be generated by cleavage after Asp121. These antibodies were used to localize cleavage events at Asp121 in post-mortem CADASIL and control brain tissue and to investigate factors that regulate cleavage at Asp121. We report that cleavage at Asp121 occurs at a high level in the arterial media of CADASIL cerebral arteries. Leptomeningeal arteries demonstrated substantially more cleavage product than penetrating arteries in the white matter, and control vessels harbored only a small amount of cleaved NOTCH3. Proteolysis at Asp121 occurred in purified preparations of NOTCH3 ectodomain, was increased by acidic pH and reductive conditions, and required native protein conformation for cleavage. Increasing the concentration of NOTCH3 EGF-like domain protein elevated the level of proteolysis. On the other hand, several polyanionic chemicals potently blocked cleavage at Asp121. These studies demonstrate that the NOTCH3 protein in CADASIL is cleaved in multiple locations at labile Asp-Pro peptide bonds. As such, chronic brain vascular disease, like other neurodegenerative conditions, features proteolysis of pathological proteins at multiple sites which may generate small pathological peptides.

Abstract Peritumoral edema (PE) of breast cancer at T2-weighted MR images is considered a poor prognostic sign and may represent the microenvironment surrounding the tumor; however, its histopathological mechanism remains unclear. The purpose of the study was to identify and describe detailed histopathological characteristics associated with PE at preoperative breast MRI in breast cancer patients. This retrospective study included breast cancer patients who had undergone preoperative MRI and surgery between January 2011 and December 2012. Two radiologists determined the presence of PE in consensus based on the signal intensity surrounding the tumor at T2-weighted images. The following detailed histopathological characteristics were reviewed by two breast pathologists using four-tiered grades; lymphovascular invasion, vessel ectasia, stromal fibrosis, growth pattern, and tumor budding. Tumor necrosis and tumor infiltrating lymphocytes were assessed using a percent scale. Baseline clinicopathological characteristics, including age and histologic grade, were collected. The associations between detailed histopathologic characteristics and PE were examined using multivariable logistic regression with odds ratio (OR) calculation. A total of 136 women (median age, 49 ± 9 years) were assessed; among them 34 (25.0%) had PE. After adjustment of baseline clinicopathological characteristics that were significantly associated with PE (age, T stage, N stage, histologic grade, and subtype, all Ps

Purpose: Approval of eribulin for metastatic breast cancer was based on data primarily from Western patients, and there is a paucity of data on the effectiveness and safety of eribulin for Asian patients. To determine the effectiveness and safety of eribulin in Korean women with breast cancer in a real-world setting, we conducted a nationwide, multicenter, retrospective study. Methods: Patients with locally advanced or metastatic breast cancer who were treated with eribulin in 14 centers throughout Korea were included in this study. Eribulin was generally administered at a dose of 1.23 mg/m2 (equivalent to 1.4 mg/m2 eribulin mesylate) by intravenous infusion for 2–5 min, or as a diluted solution, on Days 1 and 8 of every 21-day cycle. The primary endpoint was progression-free survival (PFS) rate at 6 months. Secondary endpoints included median PFS, overall survival (OS), time-to-treatment failure (TTF), tumor response rate, and incidence of hematologic treatment-emergent adverse events (TEAEs). Results: The safety and full analysis populations included 398 and 360 (38 had no efficacy data) patients, respectively. The PFS rate at 6 months was 37.8%. Median PFS, OS, and TTF were 134, 631, and 120 days, respectively. Objective response rate, clinical benefit rate, and disease control rate were 18.1%, 50.6%, and 49.4%, respectively. Hematologic TEAEs were reported in 65.1% of patients; neutropenia (56.8%) and anemia (11.3%) were most common. Conclusion: Real-world effectiveness and safety of eribulin in Korean breast cancer patients were consistent with previous reports; no new safety concerns were identified.

BackgroundThe American Joint Committee on Cancer (AJCC) guideline recommends the evaluation of ≥10 axillary lymph nodes (ALN) in patients with breast cancer to assess the N stage. However, the total ALN count in ALN dissection (ALND) often decreases after neoadjuvant chemotherapy in breast cancer. The authors compared clinicopathological factors and oncological outcomes between

Intracellular trafficking of Notch and Notch ligands modulates signaling, suggesting that choreography of ligand and receptor translocation is essential for optimal Notch activity. Indeed, a major model for Notch signaling posits that Notch trans-endocytosis into the ligand-expressing (signal sending) cell is a key driving force for Notch signal transduction. The extracellular protein thrombospondin-2 (TSP2) enhances Notch signaling and binds to both Jaggedi and Notch3 ectodomains, potentially bridging two essential extracellular components of Notch signaling. We investigated the role of low density lipoprotein receptor-related protein-1 (LRP1), a TSP2 receptor, in the regulation of Notch3 signaling. TSP2 potentiation of Notch is blocked by the receptor-associated protein (an inhibitor of low density lipoprotein receptor-related protein function) and requires LRP1 expression in the signal-sending cell. TSP2 stimulates Notch3 endocytosis into wild type fibroblasts but not LRP1-deficient fibroblasts. Finally, recombinant Notch3 and Jagged 1 interact with the LRP1 85-kDa B-chain, a subunit that lacks known ligand binding function. Our data suggest that LRP1 and TSP2 stimulate Notch activity by driving trans-endocytosis of the Notch ectodomain into the signal-sending cell and demonstrate a novel, non-cell autonomous function of LRP1 in cell-cell signaling. [ABSTRACT FROM AUTHOR]

Abstract Background Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is a predictor of improved outcomes in breast cancer. In patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) -negative breast cancer, the response to NAC is variable and mostly limited. This study was an investigation of the predictive relevance of parameters of 18F-FDG PET/CT for the pCR to NAC in patients with HR-positive, HER2–negative breast cancer. Methods: AH total of 109 consecutive HR-positive and HER2-negative breast cancer patients who were treated with NAC were enrolled in this prospective cohort study. The relationships between pretreatment 18F-FDG PET/CT and clinical outcomes including pathologic response to NAC were evaluated. Results: All patients finished their planned NAC cycles and eight patients (7.3%) achieved pCR. In the receiver operating characteristic (ROC) curve analysis, pSUVmax exhibited high sensitivity and specificity for predicting pCR. Furthermore, multivariate logistic regression analysis revealed pSUVmax as a predictive factor for pCR (hazard ratio = 17.452; 95% CI = 1.847–164.892; p = 0.013). Conclusion The results of this study suggest that 18F-FDG PET/CT pSUVmax is a predictive factor for pCR of HR-positive, HER2-negative breast cancer to NAC.

Background: The authors compared the clinical features between familial (non-hereditary) and hereditary breast cancer. And we also analyzed their oncologic outcomes to establish appropriate surveillance protocol for familial (non-hereditary) and hereditary breast cancer. Methods: Among 232 patients with breast cancer who were performed BRCA gene evaluation, twenty-eight patients were diagnosed as hereditary breast cancer with BRCA gene mutation and one-hundred and seventy-six patients were familial (non-hereditary) breast cancer. The clinical characteristics and oncologic outcomes were compared between two groups. Results: While the incidence of multifocality was higher in familial (non-hereditary) breast cancer group (p

Systemic therapy for metastatic triple-negative breast cancer (TNBC) still remains challenging because there are no targeted agents or endocrine therapies currently available. The present case report documents the successful use of cisplatin monotherapy to manage a heavily pretreated TNBC patient showing poor response to therapy. The patient was a 51-year-old woman who had already undergone several lines of systemic chemotherapy for widespread TNBC. Although the mutation analysis performed on DNA isolated from blood cells and progressed lesion samples confirmed the tumor to be germline BRCA wild-type, cisplatin monotherapy was administered based on the increasing evidence of safety and efficacy of platinum for breast cancer. After three cycles of cisplatin treatment, the patient’s metastatic lesions dramatically improved without any major toxicity, and she completed 17 cycles with good response. This case study indicates that patients with heavily pretreated TNBC can potentially achieve a good response to cisplatin monotherapy.

Background Prophylactic central neck dissection (CND) in clinically node-negative (cN0) papillary thyroid carcinoma (PTC) remains controversial. The purpose of this study was to evaluate the benefits of prophylactic ipsilateral CND compared with bilateral CND in total thyroidectomy for cN0 unilateral PTC. Methods We retrospectively enrolled 174 patients who underwent total thyroidectomies with prophylactic CND for cN0 unilateral PTC between January 2009 and May 2010. The prophylactic CND patients were divided into group 1, the ipsilateral CND group (n=74), and group 2, the bilateral CND group (n=100). The incidence of central lymph node metastasis (CLNM) and postoperative complications, such as hypoparathyroidism, recurrent laryngeal nerve injury, and recurrence were assessed. Results CLNM was found in 22 (29.8%) in group 1 and 69 (69%) in group 2. The incidence of postoperative severe hypocalcemia less than 7.0 was also significantly different (six patients [8.1%] in group 1 and 23 [23%] in group 2; p=0.009). Permanent hypoparathyroidism was significantly more frequent in group 2 (4.1% vs. 19%; p=0.005). However, the incidence of transient hypoparathyroidism, recurrence, and recurrent laryngeal nerve injury was not significantly different. Conclusion Prophylactic ipsilateral CND has advantage not only to reduce incidence of some complications but also to have similar recurrence rate compared with bilateral CND. We suggest that prophylactic ipsilateral CND may be safe and effective for selected patients undergoing total thyroidectomy for cN0 unilateral PTC.

Summary: Background/Objective: Neoadjuvant chemotherapy (NAC) is a standard treatment for locally advanced breast cancer, especially for HER2-positive or triple negative breast cancer which shows good response to chemotherapy. However, because a result of biomarkers is, occasionally, changed after NAC, the treatment strategy should be differently applied for patients with locally advanced breast cancer. We compared the results of biomarkers before and after NAC to evaluate the association with disease prognosis and oncologic results. Methods: Fifty-seven patients with locally advanced breast cancer underwent NAC and the immunohistochemical (IHC) staining results were compared between before and after NAC. And the association between oncologic outcomes and biomarkers was analyzed. Results: Negative status of estrogen receptor (ER) was associated with locoregional recurrence and distant metastasis both before and after NAC (p = 0.021, 0.019; p = 0.018, 0.036). And the negative status of progesterone receptor (PR) and triple negative status before neoadjuvant chemotherapy were also associated with death and distant metastasis, respectively. However, the changes of biomarkers after NAC in breast cancer were not directly associated with any oncologic outcomes. Conclusion: The absence of ER in breast cancer before and after NAC would be a significant prognostic factor for local recurrence and distant metastasis. Therefore, the absence of ER should be considered as important factor in determining the treatment strategy. Keywords: Neoadjuvant chemotherapy, Breast cancer, Biomarkers, Estrogen receptor

The mainstay of schizophrenia treatment is pharmacological therapy using various antipsychotics including first- and second-generation antipsychotics which have different pharmacokinetic and pharmacodynamic property leading to differential presentation of adverse events (AEs) and treatment effects such as negative symptoms, cognitive symptoms and cormorbid symptoms. Major treatment guidelines suggest the use of antipsychotic monotherapy (APM) as a gold standard in the treatment of schizophrenia. However, the effects of APM is inadequate and less potent to achieve symptom remission as well as functional recovery in real practice which has been consistently reported in numerous controlled clinical trials, large practical trials, independent small studies and systematic reviews till today. Therefore antipsychotic polypharmacy (APP) regardless of the class of antipsychotics has been also commonly utilized for many reasons in real world practice. However, APP has also crucial pitfalls including increase of total psychotics including antipsychotics, high-doses of antipsychotics used, poor compliance, drug-drug interaction and risks for developing AEs, all of which are paradoxically related to poor clinical outcomes, whereas APP has also substantial advantages in reduction of re-hospitalization, severe psychopathology and targeted control of concurrent symptoms. Given currently limited therapeutic options, it is also important to properly utilize APP in order to maximize its clinical utility and minimize its risk for better treatment outcomes for patients with schizophrenia, based on risk/benefit with full understanding of pharmacological and clinical issues on APP. The present paper intends to address intriguing and important issues in the use of APP in real world practice. [ABSTRACT FROM AUTHOR]

Objectives: Desflurane may be useful for ambulatory anesthesia. However, desfluraneinduced airway irritability makes its use challenging, especially in children. Ketamine can be used to reduce separation anxiety and emergence agitation (EA). However, ketamine may increase bronchial secretions. This study compared desflurane with sevoflurane anesthesia, in terms of emergence time and EA, in preschool children with intravenous (IV) ketamine premedication. Methods: Fifty-six children were scheduled for elective epiblepharon surgery. In the waiting room, ketamine (1 mg/kg) was intravenously administered to patients to reduce separation anxiety. After transport to the operating room, general anesthesia was induced with sevoflurane. The anesthetic agent was changed to desflurane in the desflurane group (group D), while sevoflurane was continued in the sevoflurane group (group S) during surgery. Emergence time (time to gag reflex and time to extubation) and EA (measured using the Pediatric Anesthesia Emergence Delirium [PAED] scale) were compared between the two groups. Respiratory complications were also recorded. Results: Time to gag reflex (611.1 ± 288.9 s vs. 275.0 ± 126.7 s, P < 0.001) and time to extubation (756.3±267.2 s vs. 425.9±122.9 s, P <0.001) were significantly shorter in group D than group S. EA did not differ between the two groups. There were no severe respiratory complications. Conclusions: Emergence time was shorter for desflurane anesthesia than sevoflurane anesthesia in preschool children who received IV ketamine premedication. Desflurane anesthesia with IV 0.1 mg/kg of ketamine premedication could be used safely in pediatric ophthalmic surgery; there were no significant respiratory events. [ABSTRACT FROM AUTHOR]

AIM: To compare contrast sensitivity (CS) based on the surgical results for intermittent exotropia (IXT) and to examine the relationship between CS and photophobia. METHODS: Medical records of the patients who underwent bilateral lateral rectus muscle recession for IXT between 4 and 12 years old were reviewed retrospectively. They were categorized based on the surgical results; successful correction group (n=36) and overcorrection group (esotropia ≥10 PD at 3mo postoperatively, n=18). Using CGT-2000 test for CS was performed binocularly, and subjective reports of photophobia was investigated preoperatively and at 3mo postoperatively. Objective photophobia was defined as a significant decrease in CS in the presence of glare. RESULTS: Preoperatively, there was no difference in CS between the groups. Postoperatively, under mesopic conditions, significant improvement of CS was observed at 6.3°, 4°, and 2.5° in the successful correction group and at 6.3° and 4° in the overcorrection group, regardless of glare. Under photopic conditions, at all visual angles except 0.64°, improvement in CS was noted in both groups while CS worsened significantly at 0.64° in the overcorrection group postoperatively. At all visual angles under photopic conditions postoperatively, regardless of glare, CS in the overcorrected group was significantly worse than that in the successful correction group, and CS was significantly decreased by addition of glare in both groups. All patients except one (96.4%) in the successful correction group and 8 patients (61.5%) in overcorrection group showed improvement of photophobia postoperatively, which correlated with CS under photopic conditions (P=0.001, 0.03). CONCLUSION: After surgery for IXT, CS under photopic conditions improve at all visual angles except 0.64°, while CS is significantly worse in the overcorrection group postoperatively at 0.64°. Subjective photophobia have significant correlation with CS under photopic conditions, and may be used as an objective indicator of photophobia.

Abstract Background We report on our experience of ultrasound (US)-guided dual-localization for axillary nodes before and after neoadjuvant chemotherapy (NAC) with clip and activated charcoal to guide axillary surgery in breast cancer patients. Methods Between November 2017 and May 2018, a dual-localization procedure was performed under US guidance for the most suspicious axillary nodes noted at initial staging (before NAC, with clip) and restaging (after NAC, with activated charcoal) in 28 cytologically proven node-positive breast cancer patients. Patients underwent axillary sampling or dissection, which involved removing not only the sentinel nodes (SNs), but also clipped nodes (CNs) and tattooed nodes (TNs). Success (or failure) rates of biopsies of SNs, CNs, and TNs and inter-nodal concordance rates were determined. Sensitivities for the individual and combined biopsies were calculated. Results SN biopsy failed in four patients (14%), whereas the CN biopsy failed in one patient (4%). All TNs were identified in the surgical field. Concordance rates were 79% for CNs–TNs, 63% for CNs–SNs, and 58% for TNs–SNs. Sensitivity for SN, CN, and TN biopsy was 73%, 67%, and 67%, respectively. Sensitivity was 80% for any combination of biopsies (SN plus CN, SN plus TN, SN plus CN plus TN). Conclusions US-guided dual-localization of axillary nodes before and after NAC with clip and activated charcoal was a feasible approach that might facilitate more reliable nodal staging with less-invasive strategies in node-positive breast cancer patients.

Summary: Background: axillary lymph nodes dissection (ALND) has been a standard treatment in breast cancer with positive sentinel LNs. However, various short- and long-term postoperative morbidities have been reported after conventional ALND. To define the concept of targeted axillary sampling (AS) and to assess its oncological feasibility for breast cancer. We compared the oncological outcomes in the axillary area between conventional ALND and targeted AS with or without radiotherapy. Methods: One hundred and twenty-nine female patients with cT1-2N1 breast cancer underwent breast and axillary surgery. We defined the concept of targeted AS in clinical and pathological terms, and the oncological outcomes were compared between ALND and AS, and between AS with and without radiotherapy. Results: There were no significant differences in oncological outcomes in the axilla between conventional ALND and AS, or between AS with radiotherapy and AS alone. Conclusions: The 5-year oncological outcomes of targeted AS were not inferior to those of conventional ALND, regardless of whether radiotherapy was added. Keywords: Breast, Carcinoma, Lymph node, Dissection, Sampling

Abstract Background A phase II clinical trial of the comparison between eribulin plus gemcitabine (EG) and paclitaxel plus gemcitabine (PG) as first-line chemotherapy for patients with metastatic breast cancer (MBC) found that the EG regimen was less neurotoxic, but was similar in efficacy to the PG regimen. In the present study, we analyzed functional assessment of cancer therapy-taxane (FACT-Taxane) questionnaires from patients in this clinical trial to determine their quality of life (QoL). Methods QoL was assessed using the Korean version of the FACT-Taxane questionnaires. After baseline assessment, QoL was assessed every 2 cycles for 12 cycles and every 3 cycles thereafter. The linear mixed model was used to evaluate the difference in QoL between the EG and PG arms. Results Of the 118 enrolled patients, 117 responded to the FACT-Taxane questionnaires at baseline, 1 in the PG arm did not. Baseline QoL scores were not different between the EG and PG arms. During treatment, taxane subscale scores were significantly higher in the PG arm than in the EG arm after 2–13 cycles of chemotherapy (all P

Abstract Background Gene expression profiling provides key information for prognosis of breast cancer to establish treatment strategy. However, the genetic assessment should be available before induction of treatment to be useful for clinical practice. To evaluate the reliability of using needle biopsy samples for gene assays, we compared gene-expression profiling results between core needle biopsy (CNB) samples and surgical specimens in breast cancer. Methods Thirty-one paired, formalin-fixed, paraffin-embedded CNB and surgical specimen samples were selected from patients with hormone receptor-positive breast cancer. Total RNA was extracted from the samples and the risk classifications based on GenesWell BCT scores were compared. Results The BCT scores correlated between CNB samples and surgical specimens of hormone receptor-positive breast cancer (Pearson r = 0.66). The overall concordance rate of risk classification (high/low risk) was 83.9%. However, when the breast cancer does not contain intratumoral microcalcification, the concordance rate increased as 92.0%. And, when the breast cancer formed a solitary nodule (non-multifocal), the concordance rate increased up to 95.8%. Conclusion Risk classification using the GenesWell BCT multigene kit with CNB samples could be considered reliable, when the breast cancer is a solitary nodule without intratumoral microcalcification. Such genetic profiling results should be helpful for establishing a treatment plan for hormone receptor-positive breast cancer before treatment induction.

BackgroundThe prognostic or predictive value of commonly used multigene assays in young patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer is unclear. In this study, we assessed the prognostic value of the GenesWell BCT assay according to age group.MethodsWe identified patients with pN0-1, HR+/HER2− breast cancer in a prospective cohort of women who underwent surgery between 2005 and 2017. The GenesWell BCT assay was performed on tissue samples from selected patients. Distant metastasis-free survival (DMFS) and disease-free survival (DFS) were compared between the risk groups assigned by the BCT score.ResultsA total of 712 patients were eligible for analysis. The median follow-up time was 7.47 years. The BCT score was prognostic in patients aged ≤50 years (n = 404) and those aged >50 years (n = 308). In both age groups, the 10-year DMFS and DFS rates for patients classified as high risk by the BCT score were significantly lower than those for patients classified as low risk. A multivariate analysis revealed that the BCT score was an independent prognostic factor for DFS in patients aged ≤50 years (hazard ratio, 1.28; 95% CI, 1.05–1.56; P = 0.015), as well as those aged >50 years.ConclusionThe BCT score could be used to identify low-risk patients who will not benefit from adjuvant chemotherapy to treat HR+/HER2− early breast cancer regardless of age. A further prospective study to assess the prognostic and predictive value of the BCT score is required.

Cysteine oxidation states of extracellular proteins participate in functional regulation and in disease pathophysiology. In the most common inherited dementia, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), mutations in NOTCH3 that alter extracellular cysteine number have implicated NOTCH3 cysteine states as potential triggers of cerebral vascular smooth muscle cytopathology. In this report, we describe a novel property of the second EGF-like domain of NOTCH3: its capacity to alter the cysteine redox state of the NOTCH3 ectodomain. Synthetic peptides corresponding to this sequence (NOTCH3 N-terminal fragment 2, NTF2) readily reduce NOTCH3 N-terminal ectodomain polypeptides in a dose- and time-dependent fashion. Furthermore, NTF2 preferentially reduces regional domains of NOTCH3 with the highest intensity against EGF-like domains 12–15. This process requires cysteine residues of NTF2 and is also capable of targeting selected extracellular proteins that include TSP2 and CTSH. CADASIL mutations in NOTCH3 increase susceptibility to NTF2-facilitated reduction and to trans-reduction by NOTCH3 produced in cells. Moreover, NTF2 forms complexes with the NOTCH3 ectodomain, and cleaved NOTCH3 co-localizes with the NOTCH3 ectodomain in cerebral arteries of CADASIL patients. The potential for NTF2 to reduce vascular proteins and the enhanced preference for it to trans-reduce mutant NOTCH3 implicate a role for protein trans-reduction in cerebrovascular pathological states such as CADASIL.

A large number of pre-clinical and developmental investigations involve experimental vertebrate animals, of which mice have emerged as a favored organism. Recognition of the differences between humans and mice is essential for assessment of the relevance of animal studies to humans. The primary purpose of this study was to gauge the conservation between human and mouse vascular smooth muscle cell (VSMC) proteins mined from an analysis of the Human Protein Atlas. Two comparison were made: a) immunohistochemistry for 16 proteins in brain, heart, esophagus, bladder, stomach, lung, kidney, and aorta enabled comparison between human and mouse of protein localization in VSMC and non-vascular SMC; and b) multi-species primary protein sequence analysis of an expanded set vascular molecules enabled comparison between VSMC sequences among vertebrate species. In total, three dimensions of diversity were uncovered. First, a significant number of factors show human/mouse differences in cellular expression; these differences occurred in both VSMC and non-vascular SMC in an organ and cell-type dependent fashion. Many markers demonstrated notable cell-to-cell and regional heterogeneity in VSMC of the aorta and non-vascular SMC of the esophagus, bladder, and stomach. Second, species specificity can arise by genetic deletions as exemplified by the human protein adipogenesis regulatory factor (ADIRF), which is not present due to a large sequence gap in mice. Third, we describe significant cross-species protein sequence divergence in selected VSMC proteins which may result in altered orthologue function. In a sample of 346 vascular molecules, 15% demonstrate incomplete vertebrate species gene conservation. Divergence of predicted human/mouse VSMC protein sequences is higher than for endothelial proteins in all species examined. In the future, each of these three cross-species differences could be neutralized using gene manipulation, resulting in improved translational potential of murine experimental models.

Protein sulfhydryl residues participate in key structural and biochemical functions. Alterations in sulfhydryl status, regulated by either reversible redox reactions or by permanent covalent capping, may be challenging to identify. To advance the detection of protein sulfhydryl groups, we describe the production of new Rabbit monoclonal antibodies that react with carbamidomethyl-cysteine (CAM-cys), a product of iodoacetamide (IAM) labeling of protein sulfhydryl residues. These antibodies bind to proteins labeled with IAM (but not N-ethylmaleimide (NEM) or acrylamide) and identify multiple protein bands when applied to Western blots of cell lysates treated with IAM. The monoclonal antibodies label a subset of CAM-cys modified peptide sequences and purified proteins (human von Willebrand Factor (gene:vWF), Jagged 1 (gene:JAG1), Laminin subunit alpha 2 (gene:LAMA2), Thrombospondin-2 (gene:TSP2), and Collagen IV (gene:COL4)) but do not recognize specific proteins such as Bovine serum albumin (gene:BSA) and human Thrombospondin-1 (gene:TSP1), Biglycan (gene:BGN) and Decorin (gene:DCN). Scanning mutants of the peptide sequence used to generate the CAM-cys antibodies elucidated residues required for context dependent reactivity. In addition to recognition of in vitro labeled proteins, the antibodies were used to identify selected sulfhydryl-containing proteins from living cells that were pulse labeled with IAM. Further development of novel CAM-cys monoclonal antibodies in conjunction with other biochemical tools may complement current methods for sulfhydryl detection within specific proteins. Moreover, CAM-cys reactive reagents may be useful when there is a need to label subpopulations of proteins.

AIM: To evaluate the prevalence, clinical features, and the factors affecting onset of strabismus and nystagmus in patients with bilateral congenital cataracts. METHODS: This study evaluated 116 eyes of 58 patients who underwent lens removal for the treatment of bilateral congenital cataracts between January 1999 and January 2011. The presence and type of strabismus and nystagmus were determined before and after surgery. Type of strabismus and final visual acuity were compared in patients with and without nystagmus. Patients were divided into three groups (orthotropia/orthotropia, orthotropia/strabismus, and strabismus/strabismus) according to their preoperative and postoperative ocular alignment. Age at cataract surgery and associations of nystagmus and primary intraocular lens (IOL) implantation with strabismus were analyzed. RESULTS: Six patients (10.3%) had strabismus preoperatively and an additional 11 (19.0%) developed postoperative strabismus. Exotropia was more common than esotropia both preoperatively and postoperatively. Eighteen patients (31.0%) had postoperative nystagmus, with sensory nystagmus being the most common type. Of the 18 patients with nystagmus, 10 had strabismus, with exotropia being more common than esotropia. Postoperative visual acuity was poor in patients with nystagmus. Age at cataract surgery and rate of primary IOL implantation were significantly lower, and postoperative nystagmus was more common, in the orthotropia/strabismus group than in the other two groups. CONCLUSION: Exotropia and sensory nystagmus are common in patients with bilateral congenital cataracts. Age at cataract surgery and rate of IOL implantation are lower and nystagmus more common in patients with postoperative onset of strabismus. Nystagmus is associated with poor visual prognosis.

It is increasingly agreed upon that cognitive and audiological factors are associated with self-perceived hearing handicap in old adults. This study aimed to compare self-perceived hearing handicap among mild cognitive impairment (MCI) subgroups and a cognitively normal elderly (CNE) group and determine which factors (i.e., demographic, audiometric, or neuropsychological factors) are correlated with self-perceived hearing handicap in each group. A total of 46 MCI patients and 39 hearing threshold-matched CNE subjects participated in this study, and their age ranged from 55 to 80 years. The MCI patients were reclassified into two groups: 16 with frontal-executive dysfunction (FED) and 30 without FED. All subjects underwent audiometric, neuropsychological, and self-perceived hearing handicap assessments. The Korean version of the Hearing Handicap Inventory for the Elderly (K-HHIE) was administered to obtain the hearing handicap scores for each subject. After controlling for age, years of education, and depression levels, we found no significant differences in the K-HHIE scores between the MCI and the CNE groups. However, after we classified the MCI patients into the MCI with FED and MCI without FED groups, the MCI with FED group scored significantly higher than did both the MCI without FED and the CNE groups. In addition, after controlling for depression levels, significant partial correlations of hearing handicap scores with frontal-executive function scores and speech-in-noise perception performance were found in the MCI groups. In the CNE group, the hearing handicap scores were related to peripheral hearing sensitivity and years of education. In summary, MCI patients with FED are more likely to experience everyday hearing handicap than those without FED and cognitively normal old adults. Although educational level and peripheral hearing function are related to self-perceived hearing handicap in cognitively normal old adults, speech-in-noise perception and frontal-executive function are mainly associated with hearing handicap in patients with MCI.

Jeotgal (醢) is a traditional Korean fermented food with thousands years of history with kimchi and other jang (fermented soybean products, 醬). The history was proved by research from historical literature and antique architecture. Jeotgal was developed along with jang (豆醬), fish jang (魚醬), meat jang (肉醬) as a part of jang (醬) up to the Chosun Dynasty and it was always offered during the ancestral rites or ceremonies. According to antique documents written by women, jeotgal had been used as seasonings or condiments that were popular especially for women rather than as food served for ancestral rites. In Southeast Asia and other countries, jeotgal uses varieties of fish and seafoods to provide rich and varied flavors, and thanks to the next generation sequencing technology, we can identify microorganisms that are involved in the fermentation process. Major microorganisms in jeotgal are Bacillus, Brevibacterium, Micrococcus, Pediococcus, Pseudomonas, Lactobacillus, Leuconostoc, and Halobacterium. Recently, much research on various health function of jeotgal has been conducted, reflecting increasing interest in the safety and the functionality of jeotgal. Many reports on functionalities of jeotgal such as supplying essential amino acids, and having antioxidant and antitumorgenic have been published recently. Because of the diverse flavor, types, and their function, jeotgal is expected to continue to develop as an important seasoning in the world sauce market.

Purpose: Long noncoding RNA, snaR (small NF90-associated RNA), has been reported to be upregulated in various cancer cell lines. We evaluated the additional role of snaR in HER2-positive breast cancer cell lines. Methods: We explored changes of expression of snaR among the selected long noncoding RNAs which have a potential in cancer proliferation or progression. The proliferation, migration, and invasion of HER2-positive breast cancer cells (SK-BR3) were evaluated by snaR with RNA interruption in 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide, wound-healing assay, and Transwell assay. Results: The expression of snaR was remarkably upregulated in SK-BR3 cell lines together with ANRIL, while the SFMBT2 was downregulated in SK-BR3 cell lines. Although Nespas, 7SK, PSF inhibiting RNA, mascRNA, Hoxa11as, NRON, AK023948, MER11C, p53 mRNA, CAR Intergenic 10, HUC 1 and 2, ZFAS1, SCA8, and SNHG5 were also upregulated and UCA1 was downregulated, the differences were not dominent. Based on the expression result, we explored the functional role of snaR in HER2-positive breast cancer. Downregulation of snaR with small interfering RNA was identified to significanlty inhibit migration as well as proliferation of SK-BR3 cells. Conclusion: In this study, snaR was identified as upregulated and to play a role in cancer progression of HER2-positive breast cancer cells. These results suggest snaR as a potential biomarker for HER2-positive breast cancer.

The human cerebrovascular system is responsible for regulating demand-dependent perfusion and maintaining the blood-brain barrier (BBB). In addition, defects in the human cerebrovasculature lead to stroke, intracerebral hemorrhage, vascular malformations, and vascular cognitive impairment. The objective of this study was to discover new proteins of the human cerebrovascular system using expression data from the Human Protein Atlas, a large-scale project which allows public access to immunohistochemical analysis of human tissues. We screened 20,158 proteins in the HPA and identified 346 expression patterns correlating to blood vessels in human brain. Independent experiments showed that 51/52 of these distributions could be experimentally replicated across different brain samples. Some proteins (40%) demonstrated endothelial cell (EC)-enriched expression, while others were expressed primarily in vascular smooth muscle cells (VSMC; 18%); 39% of these proteins were expressed in both cell types. Most brain EC markers were tissue oligospecific; that is, they were expressed in endothelia in an average of 4.8 out of 9 organs examined. Although most markers expressed in endothelial cells of the brain were present in all cerebral capillaries, a significant number (21%) were expressed only in a fraction of brain capillaries within each brain sample. Among proteins found in cerebral VSMC, virtually all were also expressed in peripheral VSMC and in non-vascular smooth muscle cells (SMC). Only one was potentially brain specific: VHL (Von Hippel-Lindau tumor suppressor). HRC (histidine rich calcium binding protein) and VHL were restricted to VSMC and not found in non-vascular tissues such as uterus or gut. In conclusion, we define a set of brain vascular proteins that could be relevant to understanding the unique physiology and pathophysiology of the human cerebrovasculature. This set of proteins defines inter-organ molecular differences in the vasculature and confirms the broad heterogeneity of vascular cells within the brain.

AIM: To evaluate factors associated with the development of strabismus after cataract extraction and primary intraocular lens implantation.METHODS: The medical records of 122 patients, aged 1.5mo to 9y, who had undergone cataract extraction with primary intraocular lens implantation between January 1993 and August 2011 were reviewed. Fourteen patients (17 eyes) with strabismus before cataract surgery were excluded. Patients were divided into those with congenital bilateral cataracts (64 patients, 128 eyes) and those with unilateral cataracts (44 patients, 44 eyes). The associations between the development of strabismus and age at cataract surgery, pre- and post-cataract extraction corrected distance visual acuity (CDVA), interocular CDVA difference, nystagmus, surgical method, and secondary cataract were evaluated.RESULTS: Factors significantly associated with the development of strabismus included age at cataract surgery (≤1y), preoperative mean CDVA ≤20/100, presence of nystagmus in the bilateral cataract group and postoperative interocular CDVA difference ＞20/70 in the unilateral group. Postoperative CDVA ≤20/100 and preservation of posterior capsule, and presence of secondary cataract were significant factors in both groups.CONCLUSION: Children with congenital cataracts should be monitored carefully after cataract surgery for the development of strabismus, especially when they underwent surgery at age ≤1y, and they have nystagmus, large postoperative interocular CDVA difference, poor preoperative and postoperative CDVA, preservation of the posterior capsule, or secondary cataract.

The peel of citrus fruit is a valuable source of flavonoids and is used in folk medicine for the curing various diseases in East Asia. In this study, 11 flavonoids and one coumarin derivative in the peel of Citrus tangerina Hort. ex Tanaka (Pyunkyul), native to Korea, were characterized using high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) and compared to the literature data. Flavanones, flavones, and the coumarin derivative were validated in terms of hesperetin, nobiletin, and coumarin levels, respectively, and quantified using the validated methods. The total concentration of the components was 4212.6 ± 37.0 mg/kg fresh peel. Naringin (1) was the most dominant component, followed by hesperidin (2). Antioxidant abilities in terms of DPPH·, ABTS·+ and reducing power were evaluated between 50 and 1000 mg/L. The antioxidant activities of the flavonoids increased in a dose-dependent manner.

Genome-wide association studies (GWASs) have already identified at least 22 common susceptibility loci associated with an increased risk of colorectal cancer (CRC). This study examined the relationship between these single nucleotide polymorphisms (SNPs) and the clinical outcomes of patients with colorectal cancer. Seven hundred seventy-six patients with surgically resected colorectal adenocarcinoma were enrolled in the present study. Twenty-two of the GWAS-identified SNPs were genotyped using a Sequenom MassARRAY. Among the 22 SNPs, two (rs1321311G>T in CDKN1A and rs10411210C>T in RHPN2) were significantly associated with the survival outcomes of CRC in a multivariate survival analysis. In a recessive model, the rs1321311 TT genotype (vs. GG + GT) and rs10411210 TT genotype (vs. CC + CT) were associated with a worse prognosis for disease-free survival (adjusted HR = 1.90; 95% confidence interval = 1.00-3.60; P = 0.050, adjusted HR = 1.94; 95% confidence interval = 1.05-3.57; P = 0.034, respectively) and overall survival (adjusted HR = 2.05; 95% confidence interval = 1.00-4.20; P = 0.049, adjusted HR = 2.06; 95% confidence interval = 1.05-4.05; P = 0.036, respectively). None of the other SNPs was significantly associated with any clinicopathologic features or survival. The present results suggest that the genetic variants of the CDKN1A (rs1321311) and RHPN2 (rs10411210) genes can be used as prognostic biomarkers for patients with surgically resected colorectal cancer.

Purpose: The purpose of this study was to determine a suitable position in which the measured length on ultrasound is close to the true renal length obtained through a multiplanar reconstructed MR image. Materials and Methods: A total of 33 individuals (males: 15, females: 18) without any underlying renal disease were included in the present study. Renal length was measured as the longest axis at the level of the renal hilum in three positions-supine, lateral decubitus, and prone, respectively. With a 3.0 T MR scanner, 3D eTHRIVE was acquired. Subsequently, the maximum longitudinal length of both the kidneys was measured through multiplanar reconstructed MR images. Paired t-test was used to compare the renal length obtained from uItrasonographic measurement with the length obtained through multiplanar reconstructed MR images. Results: Our study demonstrated significant difference between sonographic renal length in three positions and renal length through MRI (p < 0.001). However, the longest longitudinal length of right kidney among the measured three values by ultrasound was statistically similar to the renal length measured by reconstructed MR image. Among them, the lateral decubitus position showed the strongest correlation with true renal length (right: 0.887; left: 0.849). Conclusion: We recommend measurement of the maximum renal longitudinal length in all possible positions on ultrasonography. If not allowed, the best measurement is on the lateral decubitus showing the strongest correlation coefficient with true renal length. [ABSTRACT FROM AUTHOR]

Background: Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy.Methods: Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event.Discussion: This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy.Trial Registration: ClinicalTrials.gov Identifier NCT00912548 . Registered May 31 2009. Korean Breast Cancer Society Study Group Register KBCSG005 . Registered October 26 2009. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies (GWAS) represent the current frontier in pharmacogenomics. Thousands of subjects of Caucasian ancestry have been included in previous GWAS investigating antidepressant response. GWAS focused on this phenotype are lacking in Asian populations. Methods: A sample of 109 major depressive disorder (MDD) patients of Korean origin in antidepressant treatment was collected. Phenotypes were response and remission according to the Hamilton Rating Scale for Depression (HRSD). Genome-wide genotyping was performed using the Illumina Human Omni2.5-8 platform. The same phenotypes were used in the STAR*D level 1 (n = 1677) for independent replication. In order to corroborate findings and increase the comparability between the two datasets, three levels of analysis (SNPs, genes and pathways) were carried out. Bonferroni correction, permutations, and replication across samples were used to reduce the risk of false positives. Results: Among the genes replicated across the two samples (permutated p < 0.05 in both of them), CTNNA3 appeared promising. The inorganic cation transmembrane transporter activity pathway (GO:0022890) was associated with antidepressant response in both samples (p = 2.9e-5 and p = 0.001 in the Korean and STAR*D samples, respectively) and this pathway included CACNA1A, CACNA1C, and CACNB2 genes. Conclusions: The present study supported the involvement of genes coding for subunits of L-type voltage-gated calcium channel in antidepressant efficacy across different ethnicities but replication of findings is required before any definitive statement. [ABSTRACT FROM AUTHOR]

Background: Lignocellulosic biomass is an attractive renewable resource for future liquid transport fuel. Efficient and cost-effective production of bioethanol from lignocellulosic biomass depends on the development of a suitable pretreatment system. The aim of this study is to investigate a new pretreatment method that is highly efficient and effective for downstream biocatalytic hydrolysis of various lignocellulosic biomass materials, which can accelerate bioethanol commercialization. Results: The optimal conditions for the hydrogen peroxide-acetic acid (HPAC) pretreatment were 80 °C, 2 h, and an equal volume mixture of H2O2 and CH3COOH. Compared to organo-solvent pretreatment under the same conditions, the HPAC pretreatment was more effective at increasing enzymatic digestibility. After HPAC treatment, the composition of the recovered solid was 74.0 % cellulose, 20.0 % hemicelluloses, and 0.9 % lignin. Notably, 97.2 % of the lignin was removed with HPAC pretreatment. Fermentation of the hydrolyzates by S. cerevisiae resulted in 412 mL ethanol kg-1 of biomass after 24 h, which was equivalent to 85.0 % of the maximum theoretical yield (based on the amount of glucose in the raw material). Conclusion: The newly developed HPAC pretreatment was highly effective for removing lignin from lignocellulosic cell walls, resulting in enhanced enzymatic accessibility of the substrate and more efficient cellulose hydrolysis. This pretreatment produced less amounts of fermentative inhibitory compounds. In addition, HPAC pretreatment enables year-round operations, maximizing utilization of lignocellulosic biomass from various plant sources. [ABSTRACT FROM AUTHOR]

Post radiation sarcoma is a very rare and invasive malignant tumor that occurs in patients who had radiation therapy 5-10 years ago for primary cancer such as breast cancer, lung cancer or lymphoma. In recent years, the incidence of post radiation sarcoma has increased, as patients survive longer after radiation therapy. We reported a case of surgically confirmed post radiation myxofibrosarcoma from the breast of a 59-year-old woman, with a discussion on the literature. [ABSTRACT FROM AUTHOR]

Vortioxetine has a beneficial pharmacological profile for reducing anxiety and depression. Recently, a number of randomized, double-blind, placebo-controlled clinical trials (RCTs) of vortioxetine have been conducted in patients with generalized anxiety disorder (GAD); however, the results from GAD RCTs are inconsistent. With an extensive search of databases and clinical trial registries, four published short-term RCTs were identified and included in the present meta-analysis. The mean change in total scores on the Hamilton Anxiety Rating Scale (HAMA) from baseline was the primary endpoint. The secondary endpoints included the response and remission rates, as defined by a =50% reduction in HAMA total scores and a ≤7 change in the HAMA total score at the end of treatment. In addition, the mean change in the HAMA total score from baseline in the subgroup with a HAMA total score =25 at baseline was included. Vortioxetine was significantly more effective than was placebo, with a standardized mean difference (SMD) of -0.118 (95% CIs, -0.203 to -0.033, P = 0.007). In particular, those with severe GAD (HAMA total score ≥25 at baseline) had a significantly greater benefit from vortioxetine than those without (SMD = -0.338, 95% CIs = -0.552 to -0.124, p = 0.002). The odds ratios (ORs) for vortioxetine for response and remission were 1.221 (95% CIs, 1.027 to 1.452, P = 0.024) and 1.052 (95% CIs, 0.853 to 1.296, P = 0.637), respectively. Discontinuation due to adverse events (AEs) (OR = 1.560, 1.006 to 2.419, p = 0.047) was marginally higher in vortioxetine than placebo treatment, whereas discontinuation due to any reason (OR = 0.971, 0.794 to 1.187, p = 0.771) and inefficacy (OR = 0.687, 0.380 to 1.243, p = 0.215) were not significantly different among treatment groups. Although our results suggest that vortioxetine may have a potential as an another treatment option for GAD (especially for severe GAD), they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of RCTs. [ABSTRACT FROM AUTHOR]

Background: Vortioxetine was approved by the U.S. Food and Drug Administration (FDA) in September 2013 for treating major depressive disorder (MDD). Thus far, a number of randomized, double-blind, placebo-controlled clinical trials (RCTs) of vortioxetine have been conducted in patients with MDD. We performed a meta-analysis to increase the statistical power of these studies and enhance our current understanding of the role of vortioxetine in the treatment of MDD. Methods: We performed an extensive search of databases and the clinical trial registry. The mean change in total scores on the 24-item Hamilton Rating Scale for Depression (HAM-D) and the Montgomery-Åsberg Depression Rating Scale (MADRS) from the baseline were the primary outcome measures. The secondary efficacy measures were the response and remission rates, as defined by a 50% or greater reduction in HAM-D/MADRS total scores and as a score of 10 or less in the MADRS and 7 or less in the HAM-D total scores at the end of treatment. Results: We included 7 published and 5 unpublished short-term (6-12 wk) RCTs in our meta-analysis. Vortioxetine was significantly more effective than placebo, with an effect size (standardized mean difference [SMD]) of -0.217 (95% confidence interval [CI]-0.313 to-0.122) and with odds ratios (ORs) for response and remission of 1.652 (95% CI 1.321 to 2.067) and 1.399 (95% CI 1.104 to 1.773), respectively. Those treated with vortioxetine did not differ significantly from those treated with selective norepinephrine reuptake inhibitors/agomelatine with regard to the SMD of the primary outcome measure (0.081, -0.062 to 0.223) or for response (OR 0.815, 95% CI 0.585 to 1.135) and remission (OR 0.843, 95% CI 0.575 to 1.238) rates. Discontinuation owing to lack of efficacy (OR 0.541, 95% CI 0.308 to 0.950) was significantly less common among those treated with vortioxetine than among those who received placebo, whereas discontinuation owing to adverse events (AEs; OR 1.530, 95% CI 1.144 to 2.047) was significantly more common among those treated with vortioxetine than among those receiving placebo. There was no significant difference in discontinuation rates between vortioxetine and comparators owing to inefficacy (OR 0.983, 95% CI 0.585 to 1.650), whereas discontinuation owing to AEs was significantly less common in the vortioxetine than in the comparator group (OR 0.728, 95% CI 0.554 to 0.957). Limitations: Studies examining the role of vortioxetine in the treatment of MDD are limited. Conclusion: Although our results suggest that vortioxetine may be an effective treatment option for MDD, they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of heterogeneous RCTs. [ABSTRACT FROM AUTHOR]

The present study aimed to explore whether four single nucleotide polymorphisms (SNPs) within the AHI1 gene could be associated with schizophrenia (SCZ) and whether they could predict the clinical outcomes in SCZ patients treated with antipsychotics. Four hundred twenty-six (426) in-patients with SCZ and 345 controls were genotyped for four AHI1 SNPs (rs11154801, rs7750586, rs9647635 and rs9321501). Baseline and clinical measures for SCZ patients were assessed through the Positive and Negative Syndrome Scale (PANSS). Allelic and genotypic frequencies in SCZ subjects were compared with those of controls using the χ² statistics. The repeated-measure ANOVA was used for the assessment of treatment outcomes measured by PANSS changes. The case-control analysis did not show any difference in the genotypic distribution of the SNPs, while in the allelic analysis, a weak association was found between the rs9647635 A allele and SCZ. Furthermore, in the haplotype analysis, three haplotypes resulted in being associated with SCZ. On the other hand, two SNPs (rs7750586 and rs9647635) were associated with clinical improvement of negative symptoms in the allelic analysis, although in the genotypic analysis, only trends of association were found for the same SNPs. Our findings suggest a possible influence of AHI1 variants on SCZ susceptibility and antipsychotic response, particularly concerning negative symptomatology. Subsequent well-designed studies would be mandatory to confirm our results due to the methodological shortcomings of the present study. [ABSTRACT FROM AUTHOR]

Von Willebrand factor (vWF), a hemostatic protein normally synthesized and stored by endothelial cells and platelets, has been localized beyond the endothelium in vascular disease states. Previous studies have implicated potential non-hemostatic functions of vWF, but signaling mechanisms underlying its effects are currently undefined. We present evidence that vWF breaches the endothelium and is expressed in a transmural distribution pattern in cerebral small vessel disease (SVD). To determine the potential molecular consequences of vWF permeation into the vessel wall, we also tested whether vWF impairs Notch regulation of key smooth muscle marker genes. In a co-culture system using Notch ligand expressing cells to stimulate Notch in A7R5 cells, vWF strongly inhibited both the Notch pathway and the activation of mature smooth muscle gene promoters. Similar repressive effects were observed in primary human cerebral vascular smooth muscle cells. Expression of the intracellular domain of NOTCH3 allowed cells to bypass the inhibitory effects of vWF. Moreover, vWF forms molecular complexes with all four mammalian Notch ectodomains, suggesting a novel function of vWF as an extracellular inhibitor of Notch signaling. In sum, these studies demonstrate vWF in the vessel wall as a common feature of cerebral SVD; furthermore, we provide a plausible mechanism by which non-hemostatic vWF may play a novel role in the promotion of vascular disease.

Despite the fact that the majority of currently available treatment guidelines propose antidepressants as the first-line pharmacological therapy for posttraumatic stress disorder (PTSD), a substantial portion of patients fail to show an adequate response following this type of treatment. In this context, a number of small, open-label studies and randomized controlled clinical trials (RCTs) have found atypical antipsychotics (AAs) to be a beneficial treatment for patients with PTSD. Thus, the present meta-analysis was conducted to enhance the sample size power and further the current understanding of the role of AAs for the treatment of PTSD. An extensive search of several databases identified 12 appropriate RCTs and available data from 9 of these (n = 497) were included in the final meta-analysis. AAs may have potential benefits for the treatment of PTSD as indicated by changes from baseline of the total score on the Clinician Administered PTSD Scale (CAPS; standardized mean difference [SMD] = -0.289, 95% confidence intervals [CIs] = -0.471, -0.106), P = 0.002). Additionally, AAs were found to be significantly more effective (P < 0.0001) than a placebo in terms of change from baseline for the intrusion sub-score on the CAPS (SMD = -0.373, 95% CIs = -0.568, -0.178) but there were no significant reductions for the avoidance and hyperarousal sub-symptoms. The responder rate and rate of improvement of depressive symptoms were also significantly higher in the AA group than the placebo group (P = 0.004 and P < 0.0001, respectively). However, the present results should be interpreted carefully and be translated into clinical practice only with due consideration of the limited quality and quantity of existing RCTs included in this analysis. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the clinical outcome of bone marrow (BM) involvement in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy. Materials and Methods: A total of 567 consecutive patients with newly diagnosed DLBCL treated with rituximab- CHOP (RCHOP) between November 2001 and March 2010 were included in the current study. All of the patients underwent a BM study at the initial staging and the clinical characteristics and prognosis of these patients with or without BM involvement were analyzed retrospectively. Results: The total cohort included 567 patients. The overall incidence of BM involvement was 8.5%. With a median follow-up duration of 33.2 months (range, 0.1 to 80.7 months) for patients who were alive at the last follow-up, the five-year overall survival (OS) and event-free survival (EFS) rate in patients without BM involvement (76.3% and 67.5%, p<0.001) was statistically higher than that in patients with BM involvement (44.3% and 40.1%, p<0.001). In multivariate analysis, among total patients, BM involvement showed a significant association with OS and EFS. In univariate and multivariate analyses, even among stage IV patients, a significant association with worse EFS was observed in the BM involvement group. Conclusion: BM involvement at diagnosis affected the survival of patients with DLBCL who received RCHOP. Although use of RCHOP can result in significant improvement of the therapeutic effect of DLBCL, BM involvement is still a negative prognostic factor of DLBCL patients in the era of rituximab. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the psychological factors between young Korean conscripts with lumbar disc herniation (LDH) and healthy controls and to evaluate the interrelationships among pain, disability, and psychological factors in LDH conscripts. The subjects consisted of 56 young conscripts with LDH and 76 controls. All subjects completed Beck's Depression Inventory and Spielberger's State-Trait Anxiety Inventory. To evaluate pain intensity and functional disability, the Visual Analogue Scale and the Modified Oswestry Low Back Pain Disability Questionnaire were used. LDH conscripts had more depression and anxiety than the controls. The functional disability of the LDH conscripts was significantly related to the four variables: pain intensity, depression, state anxiety, and trait anxiety. Pain intensity and state anxiety significantly contributed to the functional disability in the LDH conscripts. This study suggests that LDH conscripts have some psychological problems, such as depression and anxiety, in comparison to healthy controls. Furthermore, the pain intensity and state anxiety predict the functional disability in LDH conscripts. [ABSTRACT FROM AUTHOR]

Objectives It has been suggested that oxidative injuries have an important role in the pathogenesis of Alzheimer's disease (AD). In this study, we assess whether the plasma levels of albumin, bilirubin, and uric acid would be altered in the AD patients compared to those of the healthy controls. Furthermore, we tried to find the correlations between plasma antioxidant levels and the cognitive function in AD patients. Methods The plasma albumin, bilirubin, and uric acid levels were measured by standard methods in 101 AD patients and 101 healthy controls. The Korean version of the Mini Mental Status Examination (MMSE-K) was used to evaluate the cognitive functions of AD patients. Results A significant reduction in the albumin, bilirubin, and uric acid levels in the AD group was found compared to those of the control group. The scores of MMSE-K showed the positive correlation with albumin level in the AD group after adjusting confounding factors such as body mass index, gender and age. Conclusion This study showed that oxidative injuries could be involved in the pathogenesis of AD, as well as indicating that some antioxidant might be associated with the cognitive functions in AD. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]