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Background: Immediate breast reconstruction with tissue expander in breast cancer patients who were expected to receive adjuvant therapy, such as chemotherapy or radiotherapy, has been a topic of debate. Postoperative complications from tissue expander procedures can delay the timing of adjuvant treatment and subsequently increase the probability of recurrence. The purpose of this study was to identify the impact of chemotherapy and radiotherapy on postoperative complications in patients who underwent immediate reconstruction (IR) using tissue expander.Methods: We conducted a retrospective study of 1081 breast cancer patients who underwent mastectomy and IR using tissue expander insertion between 2012 and 2017 in Samsung Medical Center. The patients were divided into two groups based on complications (complication group vs. no complication group). Complication group was regarded to have surgical removal or conservative treatment based on clinical findings such as infection, capsular contracture, seroma, hematoma, rupture, malposition, tissue viability, or cosmetic problem. The complication group had 59 patients (5.5%) and the no complication group had 1022 patients (94.5%).Results: In univariate analysis, adjuvant radiotherapy and adjuvant chemotherapy were significantly associated with postoperative complications. In multivariate analysis, however, only higher pathologic N stage was significantly associated with postoperative complications (p < 0.001). Chemotherapy (p = 0.775) or radiotherapy (p = 0.825) were not risk factors for postoperative complications.Conclusions: IR with tissue expander after mastectomy may be a treatment option even when the patients are expected to receive adjuvant chemotherapy or radiotherapy. These results will aid patients who are concerned about the complications of IR caused by chemotherapy or radiotherapy determine whether or not to have IR.Trial Registration: Patients were selected and registered retrospectively, and medical records were evaluated. [ABSTRACT FROM AUTHOR]

Purpose: This study was to evaluate changes of the mechanical loading pattern after anatomic anterior cruciate ligament (ACL) reconstruction by analyzing uptake patterns using combined single-photon emission computerized tomography and conventional computerized tomography (SPECT/CT). Materials and Methods: On SPECT/CT, high signal intensity of the articular surface which shows biological activity and mean increase of mechanical loading was compared with that of the tibiofemoral shaft as a comparative signal. The proportion of positive signals was evaluated in all compartments of the operated knee. Analysis was performed according to combined injury. Results: A relatively high proportion of positive signals was detected in the posterior zone of the lateral tibial plateau (23.5%) and trochlear groove (23.5%) although increased signal intensity was detected in all compartments. There was no statistical difference depending on the presence of combined injury and between single-bundle and double-bundle ACL reconstruction. Conclusions: Following anatomic ACL reconstruction, higher signal intensity was detected, particularly in the posterior part of the lateral tibial plateau and trochlear groove. Close observation for further signal changes or osteoarthritic changes would be required even if there was no combined injury and anatomic reconstruction was performed. [ABSTRACT FROM AUTHOR]

Background: Klebsiella pneumoniae subsp. pneumoniae KP617 is a pathogenic strain that coproduces OXA-232 and NDM-1 carbapenemases. We sequenced the genome of KP617, which was isolated from the wound of a Korean burn patient, and performed a comparative genomic analysis with three additional strains: PittNDM01, NUHL24835 and ATCC BAA-2146. Results: The complete genome of KP617 was obtained via multi-platform whole-genome sequencing. Phylogenetic analysis along with whole genome and multi-locus sequence typing of genes of the Klebsiella pneumoniae species showed that KP617 belongs to the WGLW2 group, which includes PittNDM01 and NUHL24835. Comparison of annotated genes showed that KP617 shares 98.3% of its genes with PittNDM01. Nineteen antibiotic resistance genes were identiied in the KP617 genome: blaOXA-1 and blaSHV-28 in the chromosome, blaNDM-1 in plasmid 1, and blaOXA-232 in plasmid 2 conferred resistance to beta-lactams; however, colistin- and tetracycline-resistance genes were not found. We identiied 117 virulence factors in the KP617 genome, and discovered that the genes encoding these factors were also harbored by the reference strains; eight genes were lipopolysaccharide-related and four were capsular polysaccharide-related. A comparative analysis of phage-associated regions indicated that two phage regions are speciic to the KP617 genome and that prophages did not act as a vehicle for transfer of antimicrobial resistance genes in this strain. Conclusions: Whole-genome sequencing and bioinformatics analysis revealed similarity in the genome sequences and content, and diferences in phage-related genes, plasmids and antimicrobial resistance genes between KP617 and the references. In order to elucidate the precise role of these factors in the pathogenicity of KP617, further studies are required. [ABSTRACT FROM AUTHOR]

Background: In metastatic colorectal cancer, the location of the primary tumor has been suggested to have biological significance. In this study, we investigated whether primary tumor location affects cetuximab efficacy in patients with RAS wild-type metastatic colorectal cancer.Methods: Genotyping by the SequenomMassARRAY technology platform (OncoMap) targeting KRAS, NRAS, PIK3CA, and BRAF was performed in tumors from 307 patients who had been given cetuximab as salvage treatment. Tumors with mutated RAS (KRAS or NRAS; n = 127) and those with multiple primary location (n = 10) were excluded. Right colon cancer was defined as a tumor located in the proximal part to splenic flexure.Results: A total of 170 patients were included in the study (right versus left, 23 and 147, respectively). Patients with right colon cancer showed more mutated BRAF (39.1% vs. 5.4%), mutated PIK3CA (13% vs. 1.4%), poorly differentiated tumor (17.4% vs. 3.4%), and peritoneal involvement (26.1% vs. 8.8%) than those with left colon and rectal cancer. Right colon cancer showed poorer progression-free survival (2.0 vs.5.0 months, P = 0.002) and overall survival (4.1 months and 13.0 months, P < 0.001) than the left colon and rectal cancer. By multivariable analysis, BRAF mutation, right colon primary, poorly differentiated histology, and peritoneal involvement were associated with risk of death.Conclusions: In RAS wild-type colon cancer treated with cetuximab as salvage treatment, right colon primary was associated with poorer survival outcomes than left colon and rectal cancer. [ABSTRACT FROM AUTHOR]

Background: Heartworm disease in dogs is a life-threatening parasitic disease. Although adulticide treatment with melarsomine has been proven to be the most effective, complications associated with adulticide treatment are major concerns for clinicians. Methods: This study evaluated the change in levels of D-dimer, interleukin-6, C-reactive protein and cardiac troponin I in 12 dogs with different severities of heartworm infection treated by the American Heartworm Society (AHS) recommended protocol during the treatment period. The serum levels of several markers were measured on the day of diagnosis (T-60), before the initiation of melarsomine therapy (T0), 1 day after the first injection (T1), 1 week after the first injection (T7), 1 month after the first injection (T30), 1 day after the second injection (T31), 1 day after the third injection (T32), 1 week after the third injection (T39), 1 month after the third injection (T62), 2 months after the third injection (T92), 3 months after the third injection (T122), and 6 months after the third injection (T182). Results: The serum levels of these markers were significantly different at the test time point after melarsomine treatment and also differed significantly according to the stage of heartworm disease in the dogs. Conclusion: This study found that monitoring of inflammatory and hemostatic markers in dogs with heartworm disease being treated with melarsomine might be beneficial in predicting the clinical outcomes and complications associated with melarsomine treatment. [ABSTRACT FROM AUTHOR]

Background: Enterotoxigenic Escherichia coli (ETEC) cause infectious diarrhea and diarrheal death. However, the genetic properties of pathogenic strains vary spatially and temporally, making prevention and treatment difficult. In this study, the genomic features of the major type of ETEC in Korea from 2003 to 2011 were examined by wholegenome sequencing of strain NCCP15740, and a comparative genomic analysis was performed with O6 reference strains. Results: The assembled genome size of NCCP15740 was 4,795,873 bp with 50.54% G+C content. Using rapid annotation using subsystem technology analysis, we predicted 4492 ORFs and 17 RNA genes. NCCP15740 was investigated for enterotoxin genes, colonization factor (CF) genes, serotype, multilocus sequence typing (MLST) profiles and classical and nonclassical virulence factors. NCCP15740 belonged to the O6:H16 serotype and possessed enterotoxin genes encoding heat-stable toxin (STh) and heat-labile toxin (LT); 87.5% of the O6 serotype strains possessed both toxin types. NCCP15740 carried the colonization factors CS2 and CS3, whereas most O6 strains carried CS2-CS3-CS21 (79.2%). NCCP15740 harbored fewer virulence factors (59.4%) than the average observed in other O6 strains (62.0%). Interestingly, NCCP15740 did not harbor any nonclassical virulence genes. Conclusions: The major type of ETEC in Korea had the same MLST sequence type as that of isolates from the USA obtained in 2011 and 2014, but had different colonization factor types and virulence profiles. These results provide important information for the development of an ETEC vaccine candidate. [ABSTRACT FROM AUTHOR]

Objective: The majority of studies on the associations between breastfeeding and cognitive functioning have focused on IQ, with only a few investigating learning skills, and none of the latter adjusting for maternal IQ. We examined the association between breastfeeding and learning abilities in school-aged children using a cross-sectional design. Methods: We recruited 868 children, aged 8-11 years and parents completed the Learning Disability Evaluation Scale (LDES). Multivariable linear regression models were used and age, gender, area of residence, annual family income, maternal education, and maternal age at delivery, were included as covariates. Maternal IQ was added to further adjust for the effects of maternal cognitive ability. Path analysis was conducted to investigate the mediation effect of maternal IQ between breastfeeding and learning skills. Results: Children who were ever-breastfed had higher learning quotient scores on the LDES (p = 0.001) as well as higher scores on subscales related to speaking (p = 0.001), reading (p = 0.005), writing (p = 0.004), spelling (p = 0.003), and mathematical calculation (p = 0.003) than the never-breastfed participants. All of these variables remained significant after adjusting for gestational and socioeconomic factors and for maternal IQ as covariates. The path analysis showed that breastfeeding had both indirect and direct effects on the learning quotient. Conclusions: The results suggest that breastfeeding is positively associated with learning skills in school-aged children. [ABSTRACT FROM AUTHOR]

Background: In 2015, the largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection outside the Middle East occurred in South Korea. We summarized the epidemiological, clinical, and laboratory findings of the first Korean case of MERS-CoV and analyzed whole-genome sequences of MERS-CoV derived from the patient.Case Presentation: A 68-year-old man developed fever and myalgia 7 days after returning to Korea, following a 10-day trip to the Middle East. Before diagnosis, he visited 4 hospitals, potentially resulting in secondary transmission to 28 patients. On admission to the National Medical Center (day 9, post-onset of clinical illness), he presented with drowsiness, hypoxia, and multiple patchy infiltrations on the chest radiograph. He was intubated (day 12) because of progressive acute respiratory distress syndrome (ARDS) and INF-α2a and ribavirin treatment was commenced. The treatment course was prolonged by superimposed ventilator associated pneumonia. MERS-CoV PCR results converted to negative from day 47 and the patient was discharged (day 137), following rehabilitation therapy. The complete genome sequence obtained from a sputum sample (taken on day 11) showed the highest sequence similarity (99.59%) with the virus from an outbreak in Riyadh, Saudi Arabia, in February 2015.Conclusions: The first case of MERS-CoV infection had high transmissibility and was associated with a severe clinical course. The patient made a successful recovery after early treatment with antiviral agents and adequate supportive care. This first case in South Korea became a super-spreader because of improper infection control measures, rather than variations of the virus. [ABSTRACT FROM AUTHOR]

Background: Suicide is a serious public health concern worldwide, and the fourth leading cause of death in Korea. Few studies have focused on risk factors for suicide attempt among people with suicidal ideation. The aim of the present study was to investigate the risk factors and develop prediction models for suicide attempt among people with suicidal ideation in the Korean population.Method: This study included 1567 men and 3726 women aged 20 years and older who had suicidal ideation from the Korea National Health and Nutrition Examination Survey from 2007 to 2012. Among them, 106 men and 188 women attempted suicide. Multivariate logistic regression analysis with backward stepwise elimination was performed to find risk factors for suicide attempt. Sub-group analysis, dividing participants into under 50 and at least 50 years old was also performed.Results: Among people with suicidal ideation, age, education, cancer, and depressive disorder were selected as risk factors for suicide attempt in men. Age, education, national basic livelihood security, daily activity limitation, depressive disorder, stress, smoking, and regular exercise were selected in women. Area under curves of our prediction models in men and women were 0.728 and 0.716, respectively.Conclusions: It is important to pay attention to populations with suicidal ideation and the risk factors mentioned above. Prediction models using the determined risk factors could be useful to detect high-risk groups early for suicide attempt among people with suicidal ideation. It is necessary to develop specific action plans for these high-risk groups to prevent suicide. [ABSTRACT FROM AUTHOR]

Background: Snoring is frequently associated with obstructive sleep apnea (OSA). Previous studies have shown that bone mineral density was significantly lower in patients with OSA than in controls; however, these studies did not focus on fractures. Fragility fractures can lead to long-term disabilities and a decrease in quality of life. The present study aimed to investigate the association between snoring and fragility fractures.Methods: This study included 2969 men and 3220 women aged 40 years and older from the Ansung and Ansan cohort studies in Korea. During a 10-year follow-up period, 129 and 273 fracture cases were reported in men and women, respectively.Results: Severe snoring (6-7 nights per week or sleep disturbance by snoring in the next room) was a statistically significant risk factor for fracture (p = 0.006, hazard ratio 1.68, 95% confidence interval 1.16-2.43) after adjusting for covariates related to fragility fracture in women. However, both snoring and severe snoring groups did not show significant associations with the fracture risk in men.Conclusions: Thus, information on the frequency of snoring in women may improve the accuracy of fragility fracture risk prediction, which can help in deciding whether intervention or treatment is necessary. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to investigate the long-term survival outcomes and toxicities associated with our experienced early administration of adjuvant concurrent chemoradiotherapy (CCRT).Methods: Ninety-eight patients with pelvic lymph node metastasis, positive resection margin, and/or parametrial invasion who received adjuvant CCRT between 1995 and 2011 were analyzed retrospectively. The first cycle of platinum-based adjuvant chemotherapy was initiated within 2-3 weeks after surgery (median, 12 days) and continued every 4 weeks for a total of 4 cycles. Adjuvant radiotherapy was performed during the second and third cycles of chemotherapy.Results: After a median follow-up period of 119 months for survivors, 13 patients (13.3%) experienced recurrence and 11 patients died of cancer during the follow-up period. The 5-year recurrence-free survival and cancer specific survival rates were 87.6% and 90.6%, respectively. Ninety-four patients (95.9%) received ≥3 cycles of chemotherapy. Total radiation dose of ≥45 Gy was delivered in 91 patients (92.9%). Grade 3-4 hematologic and gastrointestinal toxicities developed in 37 (37.8%) and 14 (14.3%) patients during CCRT, respectively.Conclusion: The present study confirmed the long-term safety and encouraging survival outcomes of early administration of adjuvant CCRT, suggesting the benefits of early time to initiation of adjuvant treatments. [ABSTRACT FROM AUTHOR]

Background: Due to a lack of consensus on adjuvant treatments for pT1N1 gastric cancer, surgeons face a dilemma when deciding treatments for patients with pT1N1 gastric cancer after gastrectomy. The objective of this study was to determine survival benefits of adjuvant chemotherapy and risk factors for tumor recurrence in gastric cancer patients with pT1N1.Methods: Between 1996 and 2010, 510 patients who underwent curative resection for pT1N1 gastric cancer at three institutes were divided into two groups: adjuvant chemotherapy group (N = 150) and surgery-only group (N = 360). Disease-free survival rates and risk factors for tumor recurrence were analyzed.Results: During the median follow-up of 78 months, 7.5% of patients experienced tumor recurrence (7.3% in adjuvant chemotherapy group and 7.5% in surgery-only group). The 5-year disease-free survival rate was 91.8% in the adjuvant chemotherapy group and 94.6% in the surgery-only group without significant difference between the two. In univariate analysis, older age (>65 years), male gender, body mass index <25 kg/m2, elevated gross type, and differentiated histology were associated with tumor recurrence. Multivariate analysis showed that advanced age and male gender were independent risk factors for tumor recurrence. In addition, adjuvant chemotherapy showed no benefitial effect on tumor recurrence in pT1N1 gastric cancer.Conclusions: Adjuvant chemotherapy did not show any oncologically benefitial effect on tumor recurrence, it might be unnecessary for pT1N1 gastric cancer after curative surgery. [ABSTRACT FROM AUTHOR]

Background: The Shiga toxin-producing Escherichia coli (STEC) O157 strain NCCP15739 and non-STEC O157 strain NCCP15738 were isolated from outbreaks in Korea. We characterized NCCP15739 and NCCP15738 by genome sequencing and a comparative genomic analysis using two additional strains, E. coli K-12 substr. MG1655 and O157:H7 EDL933. Results: Using the Illumina HiSeq 2000 platform and the RAST server, the whole genomes of NCCP15739 and NCCP15738 were obtained and annotated. NCCP15739 and NCCP15738 clustered with different E. coli strains based on a whole-genome phylogeny and multi-locus sequence typing analysis. Functional annotation clustering indicated enrichment for virulence plasmid and hemolysis-related genes in NCCP15739 and conjugation- and flagellum-related genes in NCCP15738. Defense mechanism- and pathogenicity-related pathways were enriched in NCCP15739 and pathways related to the assimilation of energy sources were enriched in NCCP15738. We identified 66 and 18 virulence factors from the NCCP15739 and NCCP15738 genome, respectively. Five and eight antibiotic resistance genes were identified in the NCCP15739 and NCCP15738 genomes, respectively. Based on a comparative analysis of phageassociated regions, NCCP15739 and NCCP15738 had specific prophages. The prophages in NCCP15739 carried virulence factors, but those in NCCP15738 did not, and no antibiotic resistance genes were found in the phage-associated regions. Conclusions: Our whole-genome sequencing and comparative genomic analysis revealed that NCCP15739 and NCCP15738 have specific genes and pathways. NCCP15739 had more genes (410), virulence factors (48), and phage-related regions (11) than NCCP15738. However, NCCP15738 had three more antibiotic resistance genes than NCCP15739. These differences may explain differences in pathogenicity and biological characteristics. [ABSTRACT FROM AUTHOR]

Background: To cause an economically important blast disease on rice, the filamentous fungus Magnaporthe oryzae forms a specialized infection structure, called an appressorium, to penetrate host cells. Once inside host cells, the fungus produces a filamentous primary hypha that differentiates into multicellular bulbous invasive hyphae (IH), which are surrounded by a host-derived membrane. These hyphae secrete cytoplasmic effectors that enter host cells presumably via the biotrophic interfacial complex (BIC). The first IH cell, also known as the side BIC-associated cell, is a specialized effector-secreting cell essential for a successful infection. This study aims to determine cellular processes that lead to the development of this effector-secreting first IH cell inside susceptible rice cells. Results: Using live-cell confocal imaging, we determined a series of cellular events by which the appressorium gives rise to the first IH cell in live rice cells. The filamentous primary hypha extended from the appressorium and underwent asymmetric swelling at its apex. The single nucleus in the appressorium divided, and then one nucleus migrated into the swollen apex. Septation occurred in the filamentous region of the primary hypha, establishing the first IH cell. The tip BIC that was initially associated with the primary hypha became the side BIC on the swollen apex prior to nuclear division in the appressorium. The average distance between the early side BIC and the nearest nucleus in the appressorium was estimated to be more than 32 µm. These results suggest an unknown mechanism by which effectors that are expressed in the appressorium are transported through the primary hypha for their secretion into the distantly located BIC. When M. oryzae was inoculated on heat-killed rice cells, penetration proceeded as normal, but there was no differentiation of a bulbous IH cell, suggesting its specialization for establishment of biotrophic infection. Conclusions: Our studies reveal cellular dynamics associated with the development of the effector-secreting first IH cell. Our data raise new mechanistic questions concerning hyphal differentiation in response to host environmental cues and effector trafficking from the appressorium to the BIC. [ABSTRACT FROM AUTHOR]

Background: Mucolipidosis types II and III (ML II/III) are autosomal recessive disorders caused by a deficiency in the lysosomal enzyme N-acetylglucosamine-1-phosphotransferase. We investigated the molecular genetic characteristics of the GNPTAB gene, which codes for the alpha/beta subunits of a phosphotransferase, in Korean ML II/III patients. We included prenatal tests and evaluated the spectrum of mutations in East Asian populations with ML II/III through a literature review.Methods: Seven patients from six families were enrolled in the study including two prenatal tests using chorionic villi samples. A diagnosis of ML II/III was made based on clinical findings and increases in serum lysosomal enzyme levels. PCR and direct sequencing were performed to identify GNPTAB mutations.Results: We found 14 mutant alleles including seven known mutations of c.2189delT (p.Leu730fs*7), c.1090C > T (p.Arg364*), c.2681G > A (p.Trp894*), c.3565C > T (p.Arg1189*), c.310C > T (p.Gln104*), c.1071G > A (p.Trp357*) and c.2574_2575delGA (p.Asn859Glnfs*2). Four were novel variants of unknown significance: c.992A > G (p.Tyr331Cys), c.2666 T > A (p.Leu889*), c.637-6 T > G (p.Thr213Phefs*11), and c.471_472delTT (p.Tyr158Serfs*8). Family studies revealed the probands to be compound heterozygotes. The fetuses carried the same GNPTAB mutations as the mucolipidosis II/III probands in the prenatal diagnosis.Conclusions: We identified GNPTAB mutations in all patients with ML II/III, but did not identify a hot spot in Korean patients. We successfully performed prenatal diagnosis using molecular investigation. [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]

Background: Destructive spondyloarthropathy (DSA) is one of the major complications in patients undergoing long-term hemodialysis. To the best of our knowledge, an epidural abscess occurring at the level of preexisting cervical DSA has not been well described in the literature. We report a unique case of quadriplegia caused by an epidural abscess occurring at the same level of preexisting cervical DSA.Case Presentation: A 49-year-old woman was transferred to our emergency department with 5 days of sepsis, drowsy mental status, and quadriplegia below the C5 level. The patient had a medical history of hemodialysis for 10 years. Magnetic resonance imaging showed spinal cord compression by an epidural abscess at the level of preexisting cervical DSA. Blood culture revealed methicillin-sensitive Staphylococcus aureus. Infection of the arteriovenous (AV) shunt was considered as the primary focus of sepsis and pyogenic spondylitis. We performed an emergent open door laminoplasty and the vascular team debrided the infected AV shunt site. Approximately 8 months after surgery, the patient was able to perform activities of daily living somewhat independently.Conclusions: Emergent surgical decompression and intensive medical care led to successful recovery from a septic and quadriplegic state in this patient. When diagnosing a patient who has undergone long-term hemodialysis presenting with neurologic deficits, the possibility of infectious spondylitis at the same level as DSA should be considered. [ABSTRACT FROM AUTHOR]

Oxidative stress plays an important role in the progression of various neuronal diseases including ischemia. Heat shock protein 22 (HSP22) is known to protect cells against oxidative stress. However, the protective effects and mechanisms of HSP22 in hippocampal neuronal cells under oxidative stress remain unknown. In this study, we determined whether HSP22 protects against hydrogen peroxide (H2O2)-induced oxidative stress in HT-22 using Tat-HSP22 fusion protein. We found that Tat-HSP22 transduced into HT-22 cells and that H2O2-induced cell death, oxidative stress, and DNA damage were significantly reduced by Tat-HSP22. In addition, Tat-HSP22 markedly inhibited H2O2-induced mitochondrial membrane potential, cytochrome c release, cleaved caspase-3, and Bax expression levels, while Bcl-2 expression levels were increased in HT-22 cells. Further, we showed that Tat-HSP22 transduced into animal brain and inhibited cleaved-caspase-3 expression levels as well as significantly inhibited hippocampal neuronal cell death in the CA1 region of animals in the ischemic animal model. In the present study, we demonstrated that transduced Tat-HSP22 attenuates oxidative stress-induced hippocampal neuronal cell death through the mitochondrial signaling pathway and plays a crucial role in inhibiting neuronal cell death, suggesting that Tat-HSP22 protein may be used to prevent oxidative stress-related brain diseases including ischemia. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the association between the ionotropic and glutamate receptors, N-methyl D-asparate 2A (GRIN2A) and 2B (GRIN2B), and the metabotropic glutamate receptor mGluR7 (GRM7) gene polymorphisms and attention-deficit hyperactivity disorder (ADHD) in Korean population. Methods: We conducted a case-control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test (TDT) on 149 trios, and compared scores from the continuous performance test (CPT), the Children's Depression Inventory (CDI), and the State-Trait Anxiety Inventory for Children (STAIC) according to the genotype of the glutamate receptor genes. Results: There were no significant differences in the genotype or allele frequencies of the GRIN2A rs8049651, GRIN2B rs2284411, or GRM7 rs37952452 polymorphisms between the ADHD and control groups. For 148 ADHD trios, the TDT analysis also showed no preferential transmission of the GRIN2A rs8049651 or GRIN2B rs2284411 polymorphisms. However, the TDT analysis of the GRM7 rs3792452 polymorphism showed biased transmission of the G allele (?2 = 4.67, p = 0.031). In the ADHD probands, the subjects with GG genotype in the GRM7 rs37952452 polymorphism had higher mean T-scores for omission errors on the CPT than did those with the GA or AA genotype (t = 3.38, p = 0.001). In addition, the ADHD subjects who were homozygous for the G allele in the GRM7 rs37952452 polymorphism had higher STAIC-T (t = 5.52, p < 0.001) and STAIC-S (t = 2.74, p = 0.007) scores than did those with the GA or AA genotype. Conclusions: These results provide preliminary evidence of an association between the GRM7 rs37952452 polymorphism and selective attention deficit and anxiety found within the Korean ADHD population. [ABSTRACT FROM AUTHOR]

Background: Neogenin is expressed in cap cells that have been suggested to be mammary stem or precursor cells. Neogenin is known to play an important role in mammary morphogenesis; however its relationship to tumorigenesis remains to be elucidated. Methods: To compare the expression levels of neogenin in cells with different tumorigenicity, the expression levels in M13SV1, M13SV1R2 and M13SV1R2N1 cells, which are immortalized derivatives of type I human breast epithelial cells, were evaluated. Then we measured the expression level of neogenin in paired normal and cancer tissues from eight breast cancer patients. Tissue array analysis was performed for 54 human breast tissue samples with different histology, and the results were divided into four categories (none, weak, moderate, strong) by a single well-trained blinded pathologist and statistically analyzed. Results: The nontumorigenic M13SV1 cells and normal tissues showed stronger expression of neogenin than the M13SV1R2N1 cells and the paired cancer tissues. In the tissue array, all (8/8) of the normal breast tissues showed strong neogenin expression, while 93.5% (43/46) of breast cancer tissues had either no expression or only moderate levels of neogenin expression. There was a significant difference, in the expression level of neogenin, in comparisons between normal and infiltrating ductal carcinoma (p < 0.001). Conclusion: Neogenin may play a role in mammary carcinogenesis as well as morphogenesis, and the expression may be inversely correlated with mammary carcinogenicity. The value of neogenin as a potential prognostic factor needs further evaluation. [ABSTRACT FROM AUTHOR]

Background: The incidence of breast cancer in young women (age < 35) is low. The biology of the disease in this age group is poorly understood, and there are conflicting data regarding the prognosis for these women compared to older patients. Methods: We retrospectively analyzed 2040 consecutive primary invasive breast cancer patients who underwent surgical procedures at our institution between 1990 and 1999. The younger age group was defined as patients aged <35 years at the time of diagnosis. The clinicopathological characteristics and treatment outcomes were compared between younger and older age groups. Results: A total of 256 (12.5%) patients were aged <35. There was a significantly higher incidence of nuclear grade 3 and medullary histological-type tumors in younger patients compared to older patients. Axillary lymph node status, T stage, histological grade, c-erbB2 expression and estrogen receptor status did not differ significantly between the two age groups. Younger patients had a greater probability of recurrence and death at all time periods. Although there was no significant difference in disease-free survival between the two age groups in lymph node-negative patients, the younger group showed worse prognosis among lymph node-positive patients (p < 0.001). In multivariate analysis, young age remained a significant predictor of recurrence (p = 0.010). Conclusion: Young age (<35) is an independent risk factor for relapse in operable breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: Isoprene, a volatile C5 hydrocarbon, is an important platform chemical used in the manufacturing of synthetic rubber for tires and various other applications, such as elastomers and adhesives. Results: In this study, Escherichia coli MG1655 harboring Populus trichocarpa isoprene synthase (PtispS) and the exogenous mevalonate (MVA) pathway produced 80 mg/L isoprene. Codon optimization and optimal expression of the ispS gene via adjustment of the RBS strength and inducer concentration increased isoprene production to 199 and 337 mg/L, respectively. To augment expression of MVA pathway genes, the MVA pathway was cloned on a high-copy plasmid (pBR322 origin) with a strong promoter (Ptrc), which resulted in an additional increase in isoprene production up to 956 mg/L. To reduce the formation of byproducts derived from acetyl-CoA (an initial substrate of the MVA pathway), nine relevant genes were deleted to generate the E. coli AceCo strain (E. coli MG1655 ΔackA-pta, poxB, ldhA, dld, adhE, pps, and atoDA). The AceCo strain harboring the ispS gene and MVA pathway showed enhanced isoprene production of 1832 mg/L in flask culture with reduced accumulation of byproducts. Conclusions: We achieved a 23-fold increase in isoprene production by codon optimization of PtispS, augmentation of the MVA pathway, and deletion of genes involved in byproduct formation. [ABSTRACT FROM AUTHOR]

Background: Tribbles proteins are conserved pseudokinases that function to control kinase signalling and transcription in diverse biological processes. Abnormal function in human Tribbles has been implicated in a number of diseases including leukaemia, metabolic syndromes and cardiovascular diseases. Caenorhabditis elegans Tribbles NIPI-3 was previously shown to activate host defense upon infection by promoting the conserved PMK-1/p38 mitogen-activated protein kinase (MAPK) signalling pathway. Despite the prominent role of Tribbles proteins in many species, our knowledge of their mechanism of action is fragmented, and the in vivo functional relevance of their interactions with other proteins remains largely unknown. Results: Here, by characterizing nipi-3 null mutants, we show that nipi-3 is essential for larval development and viability. Through analyses of genetic suppressors of nipi-3 null mutant lethality, we show that NIPI-3 negatively controls PMK-1/p38 signalling via transcriptional repression of the C/EBP transcription factor CEBP-1. We identified CEBP-1's transcriptional targets by ChIP-seq analyses and found them to be enriched in genes involved in development and stress responses. Unlike its cell-autonomous role in innate immunity, NIPI-3 is required in multiple tissues to control organismal development. Conclusions: Together, our data uncover an unprecedented crosstalk involving multiple tissues, in which NIPI-3 acts as a master regulator to inhibit CEBP-1 and the PMK-1/p38 MAPK pathway. In doing so, it keeps innate immunity in check and ensures proper organismal development. [ABSTRACT FROM AUTHOR]