Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival.

BACKGROUND: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is strongly associated with favorable outcome. We examined the utility of serial circulating tumor DNA (ctDNA) testing for predicting pCR and risk of metastatic recurrence. PATIENTS AND METHODS: Cell-free DNA (cfDNA) was isolated from 291 plasma samples of 84 high-risk early breast cancer patients treated in the neoadjuvant I-SPY 2 TRIAL with standard NAC alone or combined with MK-2206 (AKT inhibitor) treatment. Blood was collected at pretreatment (T0), 3 weeks after initiation of paclitaxel (T1), between paclitaxel and anthracycline regimens (T2), or prior to surgery (T3). A personalized ctDNA test was designed to detect up to 16 patient-specific mutations (from whole-exome sequencing of pretreatment tumor) in cfDNA by ultra-deep sequencing. The median follow-up time for survival analysis was 4.8 years. RESULTS: At T0, 61 of 84 (73%) patients were ctDNA positive, which decreased over time (T1: 35%; T2: 14%; and T3: 9%). Patients who remained ctDNA positive at T1 were significantly more likely to have residual disease after NAC (83% non-pCR) compared with those who cleared ctDNA (52% non-pCR; odds ratio 4.33, P = 0.012). After NAC, all patients who achieved pCR were ctDNA negative (n = 17, 100%). For those who did not achieve pCR (n = 43), ctDNA-positive patients (14%) had a significantly increased risk of metastatic recurrence [hazard ratio (HR) 10.4; 95% confidence interval (CI) 2.3-46.6]; interestingly, patients who did not achieve pCR but were ctDNA negative (86%) had excellent outcome, similar to those who achieved pCR (HR 1.4; 95% CI 0.15-13.5). CONCLUSIONS: Lack of ctDNA clearance was a significant predictor of poor response and metastatic recurrence, while clearance was associated with improved survival even in patients who did not achieve pCR. Personalized monitoring of ctDNA during NAC of high-risk early breast cancer may aid in real-time assessment of treatment response and help fine-tune pCR as a surrogate endpoint of survival.

Effect of compression fracture on trabecular bone score at lumbar spine.

Bone mineral density (BMD) may be increased due to vertebral compression fractures (VCF). Our study showed trabecular bone scores (TBS) was less affected than BMD by fractured vertebrae. The TBS of most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity, could still be used in predicting fracture risk. INTRODUCTION: Trabecular bone score (TBS), a noninvasive tool estimating bone microarchitecture, provides complementary information to lumbar spine bone mineral density (BMD). Lumbar spine BMD might be increased due to both degenerative disease and vertebral compression fractures (VCF). Lumbar spine TBS has been confirmed not influenced by osteoarthrosis, but the effects of VCF are still not been well evaluated. This study aimed to investigate whether lumbar spine TBS was affected by fractured vertebrae. METHODS: We studied postmenopausal women and men above 50 years old who underwent DXA between January 1, 2017, and May 31, 2019. By calculating the difference of BMD and TBS between L1 and the mean of L2-3, the study compared the difference of values between the control group and fracture group to determine the effects of fractured vertebrae on BMD and TBS. RESULTS: A total of 377 participants were enrolled with 202 in the control group (157 females; age: 68.06 ± 6.47 years) and 175 in the fracture group (147 females; age: 71.71 ± 9.44 years). The mean BMD of the L1 vertebrae in the fracture group was significantly higher than that in the control group (p < 0.0001). There was no significant difference between the mean differences of TBS between L1 and the means of L2-3 vertebrae in the control group and the most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity. CONCLUSION: Lumbar spine TBS, unlike BMD, is less affected by fractured vertebrae. The TBS of most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity, could still be used in predicting fracture risk.

Lifetime risks of hip fracture in patients with type 2 diabetic: Taiwan Diabetes Study.

This study is to estimate the lifetime risks of hip fracture in Chinese patients with type 2 diabetes. INTRODUCTION: The lifetime risks of hip fracture have not been reported across the age spectrum in male adults and female adults with type 2 diabetes. METHODS: A retrospective cohort study was conducted on 25275 men and 27953 women with type 2 diabetes aged 30-100 years old and participated in the National Diabetes Case Management Program in 2002-2004 in Taiwan. Sociodemographic factors, biomarkers, and comorbidity at the baseline and hip fracture events were analyzed with Cox proportional hazards regression models with age as the time scale. RESULTS: Significant differences in the lifetime risks of hip fracture were observed between men and women with type 2 diabetes. The cumulative lifetime incidences (%) of hip fracture at 50, 60, 65, 70, 75, 80, and 85 years old for men were 0.11, 0.40, 0.84, 1.84, 3.82, 8.53, and 16.72, respectively. The corresponding lifetime incidences (%) for women at 50, 60, 65, 70, 75, 80, and 85 years old were 0.05, 0.50, 1.36, 3.89, 9.56, 21.19, and 35.45, respectively. With competing risks, the significant multivariate-adjusted hazard ratio of developing hip fracture included smoking, alcohol drinking, duration of diabetes, type of oral hypoglycemic drugs use (no medication, sulfonylurea only, thiazolidinediones (TZD) only or TZD plus others, other single or multiple oral agents, insulin use, insulin plus oral hypoglycemic drug use), loop diuretics use, use of corticosteroids, normal weight or underweight, hyperlipidemia, and chronic obstructive pulmonary disease. CONCLUSIONS: The gender differences in lifetime hip fracture risk were significant. Thiazolidinediones and insulin use are factors with the greater magnitude of strength of association among those significantly associated with hip fracture.

Contamination of chicken carcasses and the abattoir environment with Listeria monocytogenes in Taiwan.

1. The following study provides the first data on the detection and types of Listeria monocytogenes isolated from broiler chickens during processing and from six Taiwanese abattoir environments.2. Listeria monocytogenes was not detected in any cloacal (n = 120) or environmental (n = 256) samples collected before and during processing, indicating that faecal material and the environment of abattoirs were not important sources of L. monocytogenes for poultry carcases. However, 28 of 246 (11.4%; 95% CI: 7.7-16.0) rinse samples collected from carcases post-evisceration from three abattoirs were positive for L. monocytogenes.3. The only serotypes detected were 1/2a (82.1%; 95% CI: 63.1-93.9) and 1/2b (14.3%; 95% CI: 4.0-32.7), with 3.6% (95% CI: 0.1-18.3) non-typable isolates.4. Characterisation by Pulsed Field Gel Electrophoresis (PFGE) identified five PFGE types, confirming cross-contamination with L. monocytogenes during evisceration, chilling and post-chilling.5. These findings highlight the potential for cross-contamination to occur through direct contact between carcases, especially whilst in chilling tanks.

[Genetic analysis of 45 patients with suspected Lynch syndrome using next-generation sequencing].

Objective: To evaluate the value of next generation sequencing (NGS) in the genetic testing of Lynch syndrome. Methods: Immunohistochemical method was used to detect the expressions of DNA mismatch repair (MMR) proteins, including MutL homolog 1 (MLH1), PMS1 homolog 2 (PMS2), MutS homolog 2 (MSH2) and MutS homolog 6 (MSH6) in colorectal cancer, gastric cancer and endometrial cancer tissues collected from Shandong Provincial Hospital between 2016 and 2018. The genomic DNA of 45 patients who were suspected with Lynch syndrome was extracted from non-cancerous tissue paraffin samples, which were postoperatively confirmed by microscope. The mutations of 12 genes including MLH1 and MSH2 were detected using NGS. The germline mutant sites and significance were analyzed by bioinformatics technology and further confirmed by using Sanger sequencing. Results: The immunohistochemical results showed that the 45 cases of suspected Lynch syndrome included 22 cases of MLH1 and PMS2 deficient expression, 16 cases of MLH2 and MSH6 deficient expression, and 7 cases of MMR proteins normal expression. The NGS result showed that 28 cases of adjacent sample from colon cancer patients included 4 cases of MLH1 pathogenic mutation, 1 case of suspected MLH1 mutation, 2 cases of MLH2 pathogenic mutation, 2 cases of suspected MLH2 mutation. No MMR gene mutation was found in adjacent samples of 6 cases of rectal cancer, 6 cases of gastric cancer and 7 cases of colorectal cancer with MMR normal expression. One case of MLH1 or MHL2 pathogenic mutation and one case of MLH1 suspected mutation was detected in adjacent samples of 5 cases of endometrial cancer. Moreover, NGS also detected many other genes mutations and unreported gene mutation sites. Pathogenic and suspected MLH1 and MSH2 mutations were verified by Sanger sequencing. Conclusions: High-throughput NGS is a quick, accurate and reliable technique to identify gene variants in suspected Lynch syndrome patients. It has a wide application prospect for gene testing of tumors associated with Lynch syndrome.

Comparison of the efficacy of electroconvulsive therapy (ECT) plus agomelatine to ECT plus placebo in treatment-resistant depression.

OBJECTIVE: Electroconvulsive therapy (ECT) is commonly used to treat patients with treatment-resistant depression. We aimed to investigate whether combining an antidepressant agent with ECT might enhance therapeutic efficacy and prevent early relapse. METHOD: During the acute ECT phase, patients (N = 97) with treatment-resistant depression were randomized to receive ECT plus agomelatine 50 mg/day (n = 48) or ECT plus placebo (n = 49). Symptom severity measures, including the 17-item Hamilton Depression Rating Scale (HAMD-17) and other scales, functional impairment, quality of life, neuropsychological tests, adverse events and attitudes toward ECT, were assessed regularly. Remission was defined as a HAMD-17 score ≤7. If patients achieved post-ECT remission, they were prescribed agomelatine 50 mg/day and participated in a 12-week follow-up trial. HAMD-17 was rated at 4-week intervals. Relapse was defined as a HAMD-17 score ≥14, or rehospitalization for a psychiatric reason. RESULTS: The two treatment groups were comparable at (i) baseline variables; (ii) score changes in all symptom measures, functional impairment, quality of life, and neuropsychological tests; (iii) frequency of adverse events and attitudes toward ECT; and (iv) post-ECT response/remission rates. There were no statistically significant differences following ECT in relapse rates and time to relapse between these two groups. CONCLUSION: Adding agomelatine to ECT yielded comparable response/remission rates to ECT without agomelatine in the acute ECT phase. Starting agomelatine in combination with ECT did not seem to be more efficacious in preventing relapse than starting agomelatine after the acute ECT course. More research is needed to guide clinical recommendations.

Prognostic impact of circumferential resection margin in esophageal cancer with or without neoadjuvant chemoradiotherapy.

The prognostic impact of circumferential resection margin (CRM) in surgically resected esophageal squamous cell carcinoma (ESCC) has been controversial. This investigation assessed the prognostic impact of CRM in surgically resected pathologic T3 ESCC patients with or without neoadjuvant chemoradiotherapy (nCRT). We reviewed consecutive p/yp T3 ESCC patients undergoing esophagectomy from two medical centers between January 2009 and December 2016. The cohort was divided into two groups: upfront esophagectomy (upfront surgery) and nCRT followed by esophagectomy (nCRT + surgery). CRM status was assessed and divided into CRM > 1 mm, 0 < CRM < 1 mm, and tumor at CRM. A total of 217 p/yp T3 ESCC patients undergoing esophagectomy (138 patients in the upfront surgery group and 79 in the nCRT + surgery group) were enrolled. In the upfront surgery group, patients with 0 < CRM < 1 mm showed equivalent overall survival to those with CRM > 1 mm (log-rank P = 0.817) and significantly outlived those with tumor at CRM (log-rank P < 0.001). However, in the nCRT + surgery group, CRM > 1 mm failed to show survival superiority to CRM between 0 and 1 mm or involved by cancer (log-rank P = 0.390). In conclusion, a negative CRM, even though being <1 mm, is adequate for pT3 ESCC patients undergoing upfront esophagectomy. In contrast, the CRM status is less prognostic in ypT3 ESCC patients undergoing nCRT followed by esophagectomy.

Survival after neoadjuvant chemoradiotherapy and oesophagectomy versus definitive chemoradiotherapy for patients with oesophageal squamous cell carcinoma.

BACKGROUND: Whether there is a difference in survival after neoadjuvant chemoradiotherapy plus surgery (CRT-S) compared with definitive chemoradiotherapy (dCRT) in patients with locally advanced oesophageal squamous cell carcinoma (SCC) remains controversial. METHODS: Patients with SCC who underwent curative treatment from 2008 to 2014 were identified from the Taiwan Cancer Registry. Propensity score matching was undertaken to balance pretreatment clinical variables. Overall survival was compared between patients undergoing CRT-S or dCRT. Univariable and multivariable analyses were performed to identify prognostic factors for overall survival. RESULTS: A total of 5832 patients with clinical stage II and III oesophageal SCC receiving CRT-S (1754) or dCRT (4078) were included. After propensity score matching, each group included 1661 patients. The 3-year overall survival rate for patients treated with CRT-S was 41·1 per cent compared with 17·9 per cent for those who had dCRT (P < 0·001). In multivariable analysis, treatment modality was an independent prognostic factor in the overall cohort before propensity score matching: hazard ratio 0·45 (95 per cent c.i. 0·40 to 0·51) for CRT-S versus dCRT (P < 0·001). In separate analyses of patients with clinical stage II and those with stage III disease, CRT-S was associated with significantly better overall survival than dCRT. CONCLUSION: Neoadjuvant chemoradiotherapy and oesophagectomy is associated with better overall survival than dCRT in patients with stage II and III oesophageal SCC.

Serum fibroblast growth factor 23 and mineral metabolism in patients with euthyroid Graves' diseases: a case-control study.

This study investigated the alterations of mineral metabolism in patients with Graves' disease (GD) who achieved euthyroidism. They had higher fibroblast growth factor 23 (FGF23) and phosphorus as compared with healthy subjects. Serum FGF23 was negatively correlated with serum phosphorus. These indicated abnormal mineral metabolism even after 1.6 years of euthyroid status. INTRODUCTION: FGF23 is involved in the mineral homeostasis, especially the regulation of serum phosphorus. Graves' disease (GD) is associated with accelerated bone turnover, hyperphosphatemia, and elevated serum FGF23. Evidence suggested that serum FGF23 decreased after a 3-month treatment of GD. However, it remains unclear whether serum FGF23, serum phosphorus, and other markers of mineral metabolism will be normalized after euthyroid status achieved. METHODS: A total of 62 patients with euthyroid GD and 62 healthy control subjects were enrolled, and the median duration of euthyroid status was 1.6 years. Endocrine profiles including thyroid function test, autoantibodies, serum FGF23, and bone turnover markers were obtained and compared between the two groups. RESULTS: Euthyroid GD patients had significantly higher serum FGF23 and phosphorus, and lower 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH) levels as compared with the control group. Serum FGF23 was significantly and negatively correlated with phosphorus level after adjusted for age, gender, calcium, iPTH, and 25(OH)D in the euthyroid GD group. CONCLUSION: Serum phosphorus and FGF23 levels remain higher in GD patients even after euthyroid status has been achieved for a median of 1.6 years. Serum FGF23 was negatively correlated with serum phosphorus in euthyroid GD patients. Underlying mechanisms warrant further investigations. TRIAL REGISTRATION: Registration number: NCT01660308 and NCT02620085.

Visit-to-visit blood pressure variability and hip fracture risk in older persons.

We investigated the association between blood pressure variability measured by the coefficient of variation (CV) of blood pressure and hip fracture in older persons with diabetes. After excluding patients with acute complications and comorbidities, a positive association with similar magnitude of strength was found between BP variability and hip fracture, compared with that in the original analysis. INTRODUCTION: Hypertension is a risk factor of osteoporosis and hip fracture, but studies have yet to investigate whether blood pressure variability measured by the CV of blood pressure can predict hip fracture in older persons with diabetes. METHODS: We conducted a retrospective cohort study on 21,160 patients who suffered from type 2 diabetes (age ≥ 50 years) and participated in the National Diabetes Care Management Program in Taiwan. The patients' 1-year variability in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the baseline and subsequent hip fracture incidence for 8.2 years were analyzed. RESULTS: There were 937 recorded incident hip fractures. SBP-CV and DBP-CV were classified based on their tertiles. After multivariate adjustment was conducted, SBP-CV found to be a predictor of hip fracture, and its hazard ratio was 1.18 (95% CI 1.00-1.40) for the third tertile compared with the first tertile. CONCLUSIONS: Our study suggests SBP stability is a predictor for hip fracture incidence in older persons with type 2 diabetes.

Clinical spectrum of glutamic acid decarboxylase antibodies in a Taiwanese population.

BACKGROUND AND PURPOSE: High levels of autoantibodies against glutamic acid decarboxylase (GAD-abs) are associated with stiff-person syndrome (SPS). However, the full clinical spectrum associated with GAD-abs in Asians is unclear. The clinical and immunological features of patients positive for GAD-abs were reviewed in a large Taiwanese series. METHODS: Retrospective case series and immunological investigations were conducted between July 2007 and July 2017 at a tertiary referral centre in Taiwan. Amongst 361 patients with GAD-ab reactivity, 185 with detailed clinical records were included. RESULTS: Twenty-seven patients (14.59%), with a mean age at assessment of 54.8 ± 13.9 years, presented with neurological symptoms. The major neurological presentations (mean GAD-ab concentrations) were SPS (n = 9, 33.3%; 135.45 ± 27.84 U/ml), cerebellar ataxia (n = 3, 11.1%; 95.61 ± 49.63 U/ml), encephalopathy (n = 2, 7.4%; 51.8 ± 49.64 U/ml) and epilepsy (n = 1, 3.7%; 83.3 U/ml). Notably, eight patients fulfilling the clinical diagnosis of multiple system atrophy had relatively lower GAD-ab concentrations (2.57 ± 0.82 U/ml), which has not been reported previously. There was no correlation between disease severity and GAD-ab concentration. Patients presenting with comorbid endocrinopathies (n = 15, 55.5%) had higher GAD-ab concentrations than those without endocrinopathies (n = 12, 44.4%; 104.45 ± 22.51 U/ml vs. 34.08 ± 21.83 U/ml, P = 0.04). Of 158 patients (85.4%) without a neurological presentation, 133 had type 1 diabetes mellitus and 20 had diabetes of other aetiologies (type 2 or gestational diabetes mellitus, or diabetes secondary to pancreatitis); the remaining four patients had pure thyroid disorders. CONCLUSIONS: A clinical and immunological evaluation of East Asian patients positive for GAD-abs is presented and a different clinical spectrum of anti-GAD syndrome is identified compared to Caucasians.

Photoinduced antibacterial activity of NRC03 peptide-conjugated dopamine/nano-reduced graphene oxide against Staphylococcus aureus.

In recent years, several drugs have become relatively easy to obtain with the rapid development of the economy and improvement in people's living standards. However, pathogenic bacteria have evolved strains that are resistant to certain drugs, such as antibiotics. Peptides are generally considered to be safe, have high tolerance to drugs, and are easy to manufacture. However, peptides are easily decomposed in complex biological environments. To solve this problem, many studies have modified peptides on the surface of nanomaterials to increase their functionality, biocompatibility, and stability. Meanwhile, nanomaterials have exhibited good absorption of near-infrared (NIR) light. When the NIR laser is focused on nanomaterials, photons are absorbed and the energy of the photons is converted into heat. Low-toxicity NRC03 peptide-conjugated dopamine/nano-reduced-graphene oxide (NRC03-DA/nRGO) nanomaterials are synthesized in this study for antibacterial testing using photothermal technology. The strains used in this study were Gram-positive Staphylococcus aureus (S. aureus). Our results indicated that the synthesized NRC03-DA/nRGO exhibits good absorption of NIR light and high photothermal conversion efficiency. Moreover, the synthesized NRC03-DA/nRGO inhibits the growth and survival of S. aureus. When the NRC03 peptide is modified on the surface of DA/nRGO, its biological stability is improved and the photothermal effect generated by NIR light produces additive effects, thereby indicating potential antibacterial applications.

Risk score prediction model for dementia in patients with type 2 diabetes.

BACKGROUND AND PURPOSE: No study has established a prediction dementia model in the Asian populations. This study aimed to develop a prediction model for dementia in Chinese type 2 diabetes patients. METHODS: The retrospective cohort study included 27 540 Chinese type 2 diabetes patients (aged 50-94 years) enrolled in the Taiwan National Diabetes Care Management Program. Participants were randomly allocated into derivation and validation sets at a 2:1 ratio. Cox proportional hazards regression models were used to identify risk factors for dementia in the derivation set. Steps proposed by the Framingham Heart Study were used to establish a prediction model with a scoring system. RESULTS: The average follow-up was 8.09 years, with a total of 853 incident dementia cases in the derivation set. The dementia risk score summed up the individual scores (from 0 to 20). The areas under the curve of 3-, 5- and 10-year dementia risks were 0.82, 0.79 and 0.76 in the derivation set and 0.84, 0.80 and 0.75 in the validation set, respectively. CONCLUSIONS: The proposed score system is the first dementia risk prediction model for Chinese type 2 diabetes patients in Taiwan.

Early improvement in PANSS-30, PANSS-8, and PANSS-6 scores predicts ultimate response and remission during acute treatment of schizophrenia.

OBJECTIVE: PANSS-8 and PANSS-6 are derived from the 30-item Positive and Negative Syndrome Scale (PANSS-30). We investigate whether PANSS-8 or PANSS-6 is a reliable, valid, sensitive to change measure, and scalable, and whether early improvement using them can predict response/remission. METHOD: Data were from 3 trials for 270 schizophrenia inpatients receiving antipsychotics. Internal consistency, validity, sensitivity to change, and scalability using PANSS-30, PANSS-8, and PANSS-6 at each assessment were examined. Early improvement was defined as at least 20% reduction of PANSS-30, PANSS-8, or PANSS-6 scores at week 2. Response was defined as at least 40% reduction of PANSS-30 and remission as a score of PANSS-8 ≤ 3 on each item at endpoint. Receiver operating characteristic analysis was used to determine which rating scale had better discriminative capacity. RESULTS: PANSS-8 and PANSS-6 showed acceptable internal consistency, were highly correlated with PANSS-30, and had sensitivity to change. PANSS-8 and PANSS-6 were scalable at each assessment, except for PANSS-6 at baseline. Early improvement using PANSS-8 or PANSS-6 had comparable predictive values with that of PANSS-30 for response/remission. CONCLUSION: PANSS-8 and PANSS-6 are clinically useful measures. Early improvement, regardless of whether PANSS-30, PANSS-8, or PANSS-6 is used, is a statistically significant predictor of response/remission.

Routes of transmission of influenza A H1N1, SARS CoV, and norovirus in air cabin: Comparative analyses.

Identifying the exact transmission route(s) of infectious diseases in indoor environments is a crucial step in developing effective intervention strategies. In this study, we proposed a comparative analysis approach and built a model to simulate outbreaks of 3 different in-flight infections in a similar cabin environment, that is, influenza A H1N1, severe acute respiratory syndrome (SARS) coronavirus (CoV), and norovirus. The simulation results seemed to suggest that the close contact route was probably the most significant route (contributes 70%, 95% confidence interval [CI]: 67%-72%) in the in-flight transmission of influenza A H1N1 transmission; as a result, passengers within 2 rows of the index case had a significantly higher infection risk than others in the outbreak (relative risk [RR]: 13.4, 95% CI: 1.5-121.2, P = .019). For SARS CoV, the airborne, close contact, and fomite routes contributed 21% (95% CI: 19%-23%), 29% (95% CI: 27%-31%), and 50% (95% CI: 48%-53%), respectively. For norovirus, the simulation results suggested that the fomite route played the dominant role (contributes 85%, 95% CI: 83%-87%) in most cases; as a result, passengers in aisle seats had a significantly higher infection risk than others (RR: 9.5, 95% CI: 1.2-77.4, P = .022). This work highlighted a method for using observed outbreak data to analyze the roles of different infection transmission routes.

Antifungal activity of the bioactive substance from Bacillus atrophaeus strain HAB-5 and its toxicity assessment on Danio rerio.

The prevalence of pathogen inhibitors bacteria has motivate the study for antimicrobial compounds. Bioactive fungicide have always received considerable attention. A bacterial isolated strain HAB-5 showed antifungal activity against plant fungi. Based on morphological, physiological, biochemical and 16SrDNA sequence analysis, the strain was identified to be a Bacillus atrophaeus. This strain possessed a broad spectrum antifungal activity against various plant pathogenic fungi. Extraction of antifungal substance was performed and the crude extract had potent antifungal ability and showed great potential for swelling and inhibiting spore germination. This antifungal displayed heat stability and active in a wide pH range 5.0-10.0. Moreover no reduction was found in its activity after enzyme treatment. The toxicity test was evaluated in Danio rerio. The acute toxicity test indicated that the 24, 48, 72, 96h LC50 values of UMTLS to the zebrafish were 14.4, 13.8, 13.4, and 12.9%, respectively. Based on the results obtained in this study, antifungal substance was not toxic to zebra. Analyses of disease suppression showed that HAB-5 was effective to reduce the incidence of anthracnose symptoms on mango fruits, also prevent disease infection and protect tobacco seedling from Phytophtora nicotianae. The bioactive substance from Bacillus atrophaeus HAB-5 could be a candidate in the generation of new antifungal agents in crop.

Effect of gut stress induced by oxidized wheat gluten on the growth performance, gut morphology and oxidative states of broilers.

This study was to investigate the effect of oxidized wheat gluten (OG) on growth performance, gut morphology and its oxidative states of broilers. One hundred and eighty-day-old male broilers (10 chicks/pen) were randomly allocated into three dietary treatments: control diet (CON), diet with 8% wheat gluten (WG) and diet with 8% OG with six pens/treatment. Body weight (BW) (21 and 35 days) and average daily gain (ADG) (1-21 days and 22-35 days) decreased (p < .05) and feed conversion ratio (FCR) (1-21 days and 22-35 days) increased (p < .05) in OG treatment. Feed intake (FI) decreased (p < .05) in WG and OG treatments during 22-35 days. However, FI was not influenced by dietary treatments during 1-21 days (p > .05). The OG-fed broilers had a lower faecal pH value (p < .05) and higher faecal moisture content (p < 05) at 14, 21, 28 and 35 days. Villus height, crypt depth and V/C value were not different (p > .05) among treatments at 21 and 35 days. Lipid peroxidation (LPO) (21 and 35 days) and malondialdehyde (MDA) (35 days) content in crop of OG treatment increased (p < .05). Oxidized glutathione (GSSG) (21 days), LPO (21 and 35 days) and MDA (21 and 35 days) content in ileum of OG treatment increased (p < .05). The reduced glutathione/oxidized glutathione (GSH/GSSG) (21 days) and (GSH) (35 days) in ileum of OG treatment decreased (p < .05). The present findings indicate that OG might be a stressor for broiler gut, which could induce oxidative stress both in crop and in ileum, and the diarrhoea as well. The growth performance of broiler was consequently depressed.

Risk of age-related macular degeneration in patients with prostate cancer: a nationwide, population-based cohort study.

BACKGROUND: Prostate cancer (PC) can be related to increased systemic oxidative stress and dihydrotestosterone level, which are also reported to be involved in the pathogenesis of age-related macular degeneration (AMD). We conducted a cohort study to determine whether patients with PC have an increased risk of AMD. PATIENTS AND METHODS: Data were collected from the Taiwan Longitudinal Health Insurance Database for the 1999-2010 period. The study PC cohort comprised 22 084 patients aged ≥18 years with a first diagnosis of PC. The comparison cohort consisted of age-, occupation-, and urbanization level-matched patients at a ratio of 1 : 1. The primary outcome was the incidence of AMD, which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling. RESULTS: The mean follow-up periods (standard deviation) for the patients with AMD in the age-, occupation-, and urbanization level-matched PC cohort and non-PC cohorts were 4.69 (2.90) and 5.51 (2.82) years. The mean age of the PC cohort was 73.9 years and that of the non-PC cohort was 73.2 years, with approximately 85.9% of the patients aged >65 years. The PC cohort had a higher risk of AMD than did the propensity score-matched non-PC cohort with an adjusted hazard ratio of 1.25 (95% confidence interval, 1.12-1.39). Compared with PC cohort receiving no injection hormone therapy, the PC cohort receiving injection hormone therapy had a lower risk of AMD (adjusted hazard ratio, 0.56; 95% confidence interval, 0.41-0.76). CONCLUSION: PC is associated with an increased risk of AMD. Patients with PC receiving injected form of androgen deprivation therapy had a lower risk of AMD than patients with PC not receiving injected form of androgen-deprivation therapy.

Cell transfer technique for constructing cytological microarrays for immunocytochemical analysis.

OBJECTIVE: To evaluate the utility of a proposed cell transfer technique for constructing cytological smear microarrays and its potential applications in multiplex immunocytochemical (ICC) staining. METHODS: Ninety-six cytology smears, including two pericardial effusions, 22 ascites and 72 pleural effusions, were transferred to a 33-plex cytological microarray. Paired staining of thyroid transcription factor-1 (TTF-1) and calretinin ICC was performed in duplicate slides. RESULTS: Most of the smeared cells selected for transfer could be removed from the original slides with a minimal loss of cells and with no change in morphological features or immunoreactivity. Comparison of the staining results with immunohistochemical staining results, clinical history and histopathological reports available for each patient revealed that TTF-1 was positive in 32/33 metastatic pulmonary adenocarcinomas (PACs), 1/15 non-pulmonary adenocarcinomas and 0/45 benign effusions. The ICC results for TTF-1 on a transferred cytological microarray revealed high (97%) sensitivity and high (96.7%) specificity for the detection of metastatic PAC. CONCLUSION: Cytology microarrays can be constructed by transferring cells from serous fluid cytological smears, and cells transferred to the microarray retain their morphological integrity and immunoreactivity. Researchers can use the technique for simultaneous immunostaining of multiple specimens in studies of neoplastic or non-neoplastic diseases when available tissue samples are limited.