Influence of complications following total mastectomy and immediate reconstruction on breast cancer recurrence.

BACKGROUND: Immediate breast reconstruction is safe from an oncological perspective, but the relatively high rate of postoperative complications raises oncological concerns. The present study aimed to evaluate the potential influence of postoperative complications after immediate breast reconstruction on breast cancer recurrence and survival. METHODS: Patients with breast cancer who had total mastectomy and immediate reconstruction between 2008 and 2013 were followed for at least 5 years. The impact of postoperative complications on oncological outcomes was assessed using multivariable Cox regression analyses. RESULTS: In total, 438 patients with a median follow-up of 82 months were analysed. Five-year local recurrence-free, disease-free and overall survival rates were 95·4, 93·1 and 98·4 per cent respectively. Postoperative complications developed in the operated breast in 120 patients (27·4 per cent) and at other sites (flap donor) in 30 patients (6·8 per cent). Development of breast complications was associated with significantly increased rate of recurrence compared with no complications (16·7 versus 5·9 per cent; P = 0·002). In multivariable analysis, patients with breast complications had significantly worse disease-free survival than those with no complications (hazard ratio (HR) 2·25; P = 0·015). This remained significant in patients who received adjuvant therapy without delay (8 weeks or less after surgery) (HR 2·45; P = 0·034). CONCLUSION: Development of postoperative complications in the breast can have a negative impact on survival and recurrence after immediate reconstruction.

ANTECEDENTES: La reconstrucción mamaria inmediata es una técnica segura desde el punto de vista oncológico, pero con una tasa relativamente alta de complicaciones postoperatorias, lo que preocupa por si puede afectar a los resultados. Este estudio tuvo como objetivo evaluar la influencia potencial de las complicaciones postoperatorias tras la reconstrucción mamaria inmediata en la recidiva y la supervivencia del cáncer de mama. MÉTODOS: Se hizo un seguimiento de al menos 5 años de las pacientes a las que se realizó una mastectomía total por cáncer de mama y una reconstrucción mamaria inmediata entre 2008 y 2013. Se evaluó el impacto de las complicaciones postoperatorias en los resultados oncológicos mediante un análisis multivariables de regresión de Cox. RESULTADOS: Se analizaron 438 pacientes con una mediana de seguimiento de 82 meses. La supervivencia libre de recidiva local a 5 años, la supervivencia libre de enfermedad y la supervivencia global fueron del 95,4%, 93,1% y 98,4%, respectivamente. Hubo complicaciones postoperatorias en la mama en 120 (31,8%) pacientes y en otros lugares (zona donante de colgajo) en 30 (6,8%). La presentación de complicaciones mamarias se asoció con una tasa de recidiva significativamente mayor en comparación con el grupo de pacientes sin complicaciones (16,7% versus 5,9%, P < 0,01). En el análisis multivariable, las pacientes con complicaciones mamarias mostraron una supervivencia libre de enfermedad significativamente menor que aquellas que no padecieron complicaciones (cociente de riesgos instantáneos, hazard ratio, HR 2,25; P = 0,02). También fue significativo el porcentaje de pacientes que recibieron tratamiento adyuvantes sin demora (≤ 8 semanas después de la operación) (HR 2,45; P = 0,03). CONCLUSIÓN: El desarrollo de complicaciones postoperatorias en la mama puede impactar negativamente en la supervivencia y en la recidiva después de la reconstrucción inmediata.

Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus.

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p < 0.001) remained as significant risk factors for AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p < 0.001). RERI, AP and S, which define the strength of interactions between two risk factors, were 9.01 (95% confidence interval (CI) 1.30-16.73), 0.58 (95% CI 0.36-0.81) and 2.66 (95% CI 1.42-4.99), respectively, supporting the presence of synergistic interactions in the development of symptomatic AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE, especially in patients with high-dose corticosteroid and immunosuppressant use regardless of clinical manifestations and disease activity.

Method of breast reconstruction and the development of lymphoedema.

BACKGROUND: Several studies have demonstrated an association between immediate autologous or implant-based breast reconstruction and a reduced incidence of lymphoedema. However, few of these have ocused specifically on whether the reconstruction method affects the development of lymphoedema. The study evaluated the potential impact of breast reconstruction modality on the incidence of lymphoedema. METHODS: Outcomes of women with breast cancer who underwent mastectomy and immediate reconstruction using an autologous flap or a tissue expander/implant between 2008 and 2013 were reviewed. Arm or hand swelling with pertinent clinical signs of lymphoedema and excess volume compared with those of the contralateral side was diagnosed as lymphoedema. The cumulative incidence of lymphoedema was estimated by the Kaplan-Meier method. Clinicopathological factors associated with the development of lymphoedema were investigated by Cox regression analysis. RESULTS: A total of 429 reconstructions (214 autologous and 215 tissue expander/implant) were analysed; the mean follow-up of patients was 45·3 months. The two groups had similar characteristics, except that women in the autologous group were older, had a higher BMI, and more often had preoperative radiotherapy than women in the tissue expander/implant group. Overall, the 2-year cumulative incidence of lymphoedema was 6·8 per cent (autologous 4·2 per cent, tissue expander/implant 9·3 per cent). Multivariable analysis demonstrated that autologous reconstruction was associated with a significantly reduced risk of lymphoedema compared with that for tissue expander/implant reconstruction. Axillary dissection, a greater number of dissected lymph nodes and postoperative chemotherapy were also independent risk factors for lymphoedema. CONCLUSION: The method of breast reconstruction may affect subsequent development of lymphoedema.

Clinical outcomes and the role of adjuvant therapy sequencing in Type II uterine cancer following definitive surgical treatment.

PURPOSE OF INVESTIGATION: Because of rarity, consensus on adjuvant therapies for Type II endometrial cancers (BC) remains undefined. Reporting their institutional outcomes, the present authors assessed the impact of adjuvant therapies on recurrence and overall survival in women with 2009 FIGO Stage I-III Type II BC. MATERIAL AND METHODS: The authors identified 108 women, treated with definitive surgery between 2000-2013, with pathologically-confirmed Type II EC (non-endometrioid [NEM, n=801 and high grade endometrioid [G3EEC, n=28]) Cox proportional hazard models were used to assess the effect of prognostic variables on disease-free (DFS) and overall survival (OS). Kaplan-Meier method was used to assess survival. RESULTS: Of the 108 women, 83 (77%) were African American (AA). Fifty-nine (55%), 12 (11%), and 37 (34%) were Stage I, II, and III, respectively. Ninety-seven patients received adjuvant therapy: 52 (radiation only), four (chemotherapy only), and 40 (combined). During follow-up (median 41 months), 44 patients (41%) recurred. Five-year DFS was 53% overall (48% [NEM], 80% [G3EEC]). Five-year OS was 75% overall (68% [NEM], 95% [G3EEC]). On multivariate analysis, lower stage and adjuvant radiation improved DFS. Higher stage, NEM, and increasing age were poor prognostic indicators of OS. CONCLUSION: Representing a large single institutional cohort for Type II BC, the present study's observed sur- vival rates are consistent with previous studies, despite the relatively high frequency of carcinosarcoma and Stage III/nodal disease. The protective effect on recurrence was not lost when radiation was delayed for chemotherapy. The present results support a multimodal adjuvant approach for treating all stages of invasive NEM EC.

HLA-E and NKG2A Mediate Resistance to M. bovis BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the primary treatment for non-muscle-invasive bladder cancer (NMIBC), known to stimulate inflammatory cytokines, notably interferon (IFN)-γ. We observed that prolonged IFN-γ exposure fosters adaptive resistance in recurrent tumors, aiding immune evasion and tumor proliferation. We identify HLA-E and NKG2A, part of a novel NK and T cell checkpoint pathway, as key mediators of resistance in BCG-unresponsive NMIBC. IFN-γ enhances HLA-E and PD-L1 expression in recurrent tumors, with an enrichment of intra-tumoral NKG2A-expressing NK and CD8 T cells. CXCL9+ macrophages and dendritic cells and CXCL12-expressing stromal cells likely recruit CXCR3/CXCR4-expressing NK and T cells and CXCR7+ HLA-EHIGH tumor cells. NK and CD8 T cells remain functional within BCG-unresponsive tumors but are inhibited by HLA-E and PD-L1, providing a framework for combined NKG2A and PD-L1 blockade strategy for bladder-sparing treatment of BCG-unresponsive NMIBC.

Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients.

BACKGROUND: This study explored the impact of genetic polymorphisms in cytochrome P450 (CYP) enzymes and transporters on the plasma trough concentration of imatinib mesylate (IM) and clinical response in chronic myeloid leukemia (CML). PATIENTS AND METHODS: In total, 82 patients with CML who had been administered 400 mg IM daily for over 6 months were genotyped for 11 single-nucleotide polymorphisms in nine genes (CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC22A1, SLC22A2 and ABCG2) using blood samples. The trough imatinib concentration and clinical responses were assessed 6 months after the initiation of IM therapy. RESULTS: The CC, CA and AA genotypes in ABCG2 421C>A gave significantly different frequencies for the major molecular response (MMR) (P = 0.02). However, no significant differences were found between the genotypes of the CYP enzymes and transporters identified in this study and the imatinib plasma trough concentrations and clinical response frequencies, except for the correlation of ABCG2 with MMR. CONCLUSIONS: The results of the present study may indicate that the ABCG 421C>A genetic polymorphism influences the MMR of imatinib in patients with CML.

Genetic analysis of hybrid seed formation ability of Brassica rapa in intergeneric crossings with Raphanus sativus.

A hybridization barrier leads to the inability of seed formation after intergeneric crossings between Brassica rapa and Raphanus sativus. Most B. rapa lines cannot set intergeneric hybrid seeds because of embryo breakdown, but a B. rapa line obtained from turnip cultivar 'Shogoin-kabu' is able to produce a large number of hybrid seeds as a maternal parent by crossings with R. sativus. In 'Shogoin-kabu' crossed with R. sativus, developments of embryos and endosperms were slower than those in intraspecific crossings, but some of them grew to mature seeds without embryo breakdown. Intergeneric hybrid seeds were obtained in a 'Shogoin-kabu' line at a rate of 0.13 per pollinated flower, while no hybrid seeds were obtained in a line developed from Chinese cabbage cultivar 'Chiifu'. F(1) hybrid plants between the lines of 'Shogoin-kabu' and 'Chiifu' set a larger number of hybrid seeds per flower, 0.68, than both the parental lines. Quantitative trait loci (QTLs) for hybrid seed formation were analyzed after intergeneric crossings using two different F(2) populations derived from the F(1) hybrids, and three QTLs with significant logarithm of odds scores were detected. Among them, two QTLs, i.e., one in linkage group A10 and the other in linkage group A01, were detected in both the F(2) populations. These two QTLs had contrary effects on the number of hybrid seeds. Epistatic interaction between these two QTLs was revealed. Possible candidate genes controlling hybrid seed formation ability in QTL regions were inferred using the published B. rapa genome sequences.

Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P < 2.03 × 10(-3) were observed between LN and MYH9 in EAs (N = 4620), with the most pronounced association at rs2157257 (P = 4.7 × 10(-4), odds ratio (OR) = 1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, P = 0.0019, OR = 2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population, and presents novel insight into the potential role of MYH9 in LN in EAs.

Adjuvant capecitabine chemotherapy using a tailored-dose strategy in elderly patients with colon cancer.

BACKGROUND: This study was conducted to analyze the feasibility of adjuvant capecitabine therapy using a tailored-dose escalation strategy in elderly patients with colon cancer (CC). METHODS: CC patients (≥ 70 years of age) who received adjuvant capecitabine were enrolled. The starting dosage of capecitabine was 2000 mg/m(2)/day (days 1-14, every 3 weeks). On the second cycle, the dosage was escalated to 2500 mg/m(2)/day if the patient tolerated the first cycle. Dose intensity (DI), toxicity, and the change in quality of life (QoL) were evaluated. RESULTS: Of 82 patients enrolled, 67 completed eight cycles. Dose escalation to 2500 mg/m(2)/day was possible in 56 patients, and this dosage was maintained in 24 patients until the completion of chemotherapy (eight cycles). Forty-one patients completed therapy with a DI ≥ 1333 mg/m(2)/day [relative dose intensity (RDI) ≥ 80%]. Toxic effects were tolerable and the QoL was not compromised during treatment. Creatinine clearance < 50 ml/min and Charlson-Age comorbidity index ≥ 8 were related to a reduced capecitabine dosage (RDI < 80%). CONCLUSIONS: A tailored-dose escalation strategy was feasible in elderly CC patients receiving adjuvant capecitabine chemotherapy. Decreased renal function and an increased number of comorbidities were independently predictive of reduced administration of the capecitabine dose.

Prediction of response to entecavir therapy in patients with HBeAg-positive chronic hepatitis B based on on-treatment HBsAg, HBeAg and HBV DNA levels.

Quantitative hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) assays are emerging as effective tools of on-treatment predictors of response to antiviral agents, in addition to monitoring serum HBV DNA levels. However, the dynamic relationship between quantitative HBsAg, as well as HBeAg and HBV DNA, and the predictability of subsequent clinical outcomes during entecavir (ETV) therapy remain unclear. Eighty-two patients with HBeAg-positive chronic hepatitis B (CHB) received ETV therapy for ≥3 years. Virologic response (VR) after 3 years of ETV therapy was achieved in 73 (89.0%) patients. Among baseline and on-treatment factors, on-treatment HBV DNA levels performed better with respect to the prediction of response than HBsAg and HBeAg levels. Especially, the performance of absolute values of HBV DNA with respect to response was superior to HBV DNA decline from the baseline. The best predictive value was an absolute HBV DNA level of 2.3 log(10) IU/mL at month 6 (areas under the curve [AUROC], 0.977; 95% CI, 0.940-1.000; P < 0.001). HBeAg seroconversion after 3 years of therapy was achieved in 26 (31.7%) patients. On-treatment HBeAg levels performed better with respect to the prediction of seroconversion than HBsAg and HBV DNA levels. The best cut-off value for the HBeAg level at month 12 for the prediction of seroconversion was 0.62 log(10) PEIU/mL. Although the HBsAg level at baseline is often used to predict the antiviral potency of entecavir, on-treatment HBV DNA and HBeAg levels are more helpful for prediction of subsequent clinical outcomes in HBeAg-positive CHB patients with entecavir treatment.

Immunoglobulin D multiple myeloma: response to therapy, survival, and prognostic factors in 75 patients.

BACKGROUND: To analyze the clinical features, outcomes including efficacy of treatment, and prognostic factors of patients with immunoglobulin D multiple myeloma (IgD MM). DESIGN AND METHODS: Seventy-five patients diagnosed with IgD MM were selected from the Korean Myeloma Registry database (www.myeloma.or.kr). RESULTS: Median age was 57 years and the main presenting features were bone pain (77%). Renal function impairment and hypercalcemia were present in 40 (53%) and 20 (27%) patients. Sixty-seven patients (89%) had lambda light chains. Forty-eight patients (64%) were of stage III by International Staging System. Twenty-six patients (53%) had chromosomal abnormalities mostly by conventional cytogenetics. Thirty-nine patients (54%) were treated with vincristine, adriamycin, and dexamethasone chemotherapy; the overall response rate (ORR) of 56%. Sixteen patients (22%) received first-line chemotherapy including new drugs (bortezomib or thalidomide), with an ORR of 81%. At a median follow-up time of 28.6 months, median overall survival (OS) was 18.5 months. Age, extramedullary plasmacytoma, del(13) or hypoploidy, serum ß(2) microglobulin level, and platelet count were significant prognostic factors for OS. CONCLUSIONS: IgD MM is an aggressive disease that is usually detected at an advanced stage. Despite a positive initial response, survival after relapse was dismal. Intensive treatment strategies before and following stem cell transplantation may improve outcomes in younger patients.

Precuneus hypoperfusion plays an important role in memory impairment of patients with systemic lupus erythematosus.

The present study was designed to identify regional cerebral blood flow (rCBF) abnormalities in systemic lupus erythematosus (SLE) patients with memory impairments. Nineteen SLE patients (mean age 36.1 ± 8.6 years, range 17-47) with subjective memory complaints underwent brain single-photon emission computed tomography (SPECT). The Korean Wechsler Adult Intelligence Scale (K-WAIS) and the Rey-Kim Memory Test (RKMT) were used objectively to evaluate cognitive functions in these patients. On the basis of the Intelligence Quotient-Memory Quotient (IQ-MQ) difference score, patients were classified into two groups: those with below one standard deviation (SD) from the mean for normal subjects of comparable age and education (memory impairment, n = 6) and those with without memory impairment (non-memory impairment, n = 13). Their brain SPECT images were analyzed by statistical parametric mapping (SPM) for group comparisons. The group of SLE patients with memory impairment showed significant hypoperfusion in the right precuneus compared with those with non-memory impairment (p < 0.001). Hypoperfusion of the precuneus may play a significant role in the memory function of SLE patients. SPM analysis of brain SPECT images could be a useful and objective tool for identifying abnormal rCBF in SLE patients with memory impairment.

Industrial production of fructooligosaccharides by immobilized cells of Aureobasidium pullulans in a packed bed reactor.

Continuous production of fructooligosaccharides (FOS) by Aureobasidium pullulans immobilized on calcium alginate beads with a packed bed was investigated at a plant scale reactor. Optimum conditions were with 770 g sucrose/l, being fed at 200 l/h at 50°C which gave a productivity of 180 g FOS/l h. Initial activity was maintained for more than 100 days. The reactor was successfully scaled up to a production scale of 1.2 m(3).

Influence of chitosan coating on the liposomal surface on physicochemical properties and the release profile of nanocarrier systems.

Chitosan-coated nanoliposomes containing etofenprox or alpha-cypermethrin prepared by ultrasonic homogenization maintained a size distribution in the nanometre range. Nanoliposomes were constructed using different types and concentrations of chitosan to regulate the mean size and surface charge. As the chitosan concentration (0.1-0.5%, w/v) and the degree of deacetylation increased, surface charge also increased. The encapsulation efficiency and release profile were measured by gas chromatography. Encapsulation efficiency decreased slightly as chitosan concentration increased (0.1-0.5%, w/v). As the intrinsic surface charge or concentration of the coating material increased, the release period of the entrapped core material was extended (chitosans A and B; 0.1 and 0.3%, w/v). The results indicate that diverse preparation conditions could affect the physicochemical properties and release profile of the resulting nanocarrier systems.

Application of the combined use of ultrasonic homogenization and electro-spraying in the formation of nano carrier systems.

Chitosan-coated nano-liposomes containing etofenprox were prepared by ultrasonic homogenization (UH) and a combined use of UH and electro-spraying. The physicochemical properties of the resulting samples were examined and compared. The two methods yielded similar values and tendencies, except for encapsulation efficiency that differed by an average of 15%. In the coating process, as the chitosan concentration increased (0.1-0.5%, w/v) and the degree of deacetylation increased (chitosans A, B and C), the surface charge of the nano carrier likewise increased and carrier size distribution was altered. The encapsulation efficiency as measured by gas chromatography decreased slightly with the increasing chitosan concentration (0.1-0.5%, w/v). The results indicate that diverse preparation conditions could affect the physicochemical properties of the resulting nano carrier systems.

Investigation of papulopustular eruptions caused by cetuximab treatment shows altered differentiation markers and increases in inflammatory cytokines.

BACKGROUND: Epidermal growth factor receptor (EGFR) critically regulates tumour cell division, survival and metastasis. Agents that inhibit EGFR have been used in the treatment of advanced-stage malignancies, but cause variable cutaneous side-effects, most often papulopustular eruptions and xerosis. OBJECTIVES: We assayed expression of inflammatory cytokines [interleukin (IL)-1alpha, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, human leucocyte antigen (HLA)-DR and intercellular adhesion molecule (ICAM)-1], differentiation markers (filaggrin, involucrin and loricrin) and phosphorylated EGFRs (pEGFRs) in papulopustular eruptions to determine the association between these markers and the eruptions caused by cetuximab. PATIENTS/METHODS: Twelve papulopustular lesion biopsies were selected from patients with colon cancer who had received cetuximab treatment. Immunohistochemistry and immunofluorescence with a confocal laser scanning microscopy were performed. RESULTS: Filaggrin expression decreased and expression of involucrin, various inflammatory markers (IL-1alpha, TNF-alpha, ICAM-1 and HLA-DR) increased and the expression of pEGFR was markedly downregulated in papulopustular eruptions. In perilesions, decreased pEGFR expression was noted in hair follicles compared with interfollicular epidermis. The increase of IL-1alpha and TNF-alpha was observed in perilesions as in the lesions. CONCLUSIONS: The early inflammatory events (IL-1alpha and TNF-alpha expression) seen, and the lack of pEGFR in perilesional follicles, indicate that inflammatory events induced by EGFR inhibition may initiate papulopustular eruptions along with the altered differentiations. The decrease of filaggrin may contribute to the pathogenesis of the xerosis caused by cetuximab.

Phylogenetic evidence of noteworthy microflora from the subsurface of the former Homestake gold mine, Lead, South Dakota.

Molecular characterization of subsurface microbial communities in the former Homestake gold mine, South Dakota, was carried out by 16S rDNA sequence analysis using a water sample and a weathered soil-like sample. Geochemical analyses indicated that both samples were high in sulphur, rich in nitrogen and salt, but with significantly different metal concentrations. Microbial diversity comparisons unexpectedly revealed three distinct operational taxonomic units (OTUs) belonging to the archaeal phylum Thaumarchaeota, typically identified from marine environments, and one OTU belonging to a potentially novel phylum that fell sister to Thaumarchaeota. To our knowledge this is only the second report of Thaumarchaeota in a terrestrial environment. The majority of the clones from Archaea sequence libraries fell into two closely related OTUs and were grouped most closely to an ammonia-oxidizing, carbon-fixing and halophilic thaumarchaeote genus, Nitrosopumilus. The two samples showed neither Euryarchaeota nor Crenarchaeota members that have often been identified from other subsurface terrestrial ecosystems. Bacteria OTUs containing the highest percentage of sequences were related to sulphur-oxidizing bacteria of the orders Chromatiales and Thiotrichales. Community members of Bacteria from individual Homestake ecosystems were heterogeneous and distinctive to each community, with unique phylotypes identified within each sample.

Genetic associations of LYN with systemic lupus erythematosus.

We targeted LYN, a src-tyosine kinase involved in B-cell activation, in case-control association studies using populations of European-American, African-American and Korean subjects. Our combined European-derived population, consisting of 2463 independent cases and 3131 unrelated controls, shows significant association with rs6983130 in a female-only analysis with 2254 cases and 2228 controls (P=1.1 x 10(-4), odds ratio (OR)=0.81 (95% confidence interval: 0.73-0.90)). This single nucleotide polymorphism (SNP) is located in the 5' untranslated region within the first intron near the transcription initiation site of LYN. In addition, SNPs upstream of the first exon also show weak and sporadic association in subsets of the total European-American population. Multivariate logistic regression analysis implicates rs6983130 as a protective factor for systemic lupus erythematosus (SLE) susceptibility when anti-dsDNA, anti-chromatin, anti-52 kDa Ro or anti-Sm autoantibody status were used as covariates. Subset analysis of the European-American female cases by American College of Rheumatology classification criteria shows a reduction in the risk of hematological disorder with rs6983130 compared with cases without hematological disorders (P=1.5 x 10(-3), OR=0.75 (95% CI: 0.62-0.89)). None of the 90 SNPs tested show significant association with SLE in the African American or Korean populations. These results support an association of LYN with European-derived individuals with SLE, especially within autoantibody or clinical subsets.

Health-related quality of life among Koreans with chronic respiratory disease.

OBJECTIVE: To evaluate the health-related quality of life (HRQoL) and to identify physiological and psychosocial variables predicting the HRQoL among Korean people with chronic respiratory disease (CRD). DESIGN: A cross-sectional correlation study was done with a convenience sample of 112 participants (aged 62.9 +/- 12.9 years, forced expiratory volume in 1 second [FEV(1)%] predicted = 52.3 +/- 20.2) from the out-patient respiratory clinic of a large university hospital in Korea. HRQoL was measured using the chronic respiratory disease questionnaire (CRDQ). To identify the influencing factors, physiological (lung function, dyspnoea, symptom experience and exercise performance) and psychological (mood states and self-efficacy) variables were examined using path analysis. RESULTS: Participants had a moderate level of HRQoL, with the lowest scores in CRDQ-fatigue (3.3 +/- 1.3) and the highest in CRDQ-mastery (5.2 +/- 1.0). Anxiety and a depressive mood state (-0.38) exerted the highest influence on HRQoL, followed by self-efficacy (0.36), dyspnoea (-0.27), exercise performance (0.22) and respiratory symptoms (-0.17). CONCLUSION: Our findings emphasise the importance of a multidimensional therapeutic approach to improve HRQoL. Comprehensive interventions, including enhanced exercise performance, self-efficacy and symptom management, should be considered to improve HRQoL in Koreans with CRD.

Lack of association between ACE and bradykinin B2 receptor gene polymorphisms and ACE inhibitor-induced coughing in hypertensive Koreans.

BACKGROUND & OBJECTIVE: Angiotensin converting enzyme (ACE) inhibitors are used widely in therapy for hypertension, congestive heart failure and myocardial infarction. However, coughing, one of their major adverse effects limits their use. It is documented that Asians are more liable to coughing than Europeans. The aim of this study was to investigate genetic polymorphism involved in ACE inhibitor-induced coughing. METHODS: We monitored hypertensive subjects (n = 110) treated with ACE inhibitors, and tested for any associations between ACE inhibitor-induced coughing and polymorphisms in the genes for ACE and the bradykinin B2 receptor, which are suspected to be related to coughing. RESULTS & DISCUSSION: We found no significant differences between the groups with coughing and without coughing in the frequency of ACE I/D (Insertion/Deletion) polymorphisms. One single nucleotide polymorphism was discovered in the promoter (-58T/C) and, one in intron-exon junction upsteam of exon 2 (-59C/A), of the bradykinin B2 receptor gene. However, no significant correlation was found between those genotypes or allele distributions and ACE inhibitor-induced coughing. CONCLUSION: We found no significant links between polymorphisms of the ACE gene or bradykinin B2 receptor gene with ACE inhibitor-induced coughing in hypertensive Koreans. But, the topic remains controversial and requires more study.