M1 Group Research Articles

Effect of Food Simulating Liquids and Thermo-cycling on flexural strength and surface hardness of a Resin Nano-Ceramic CAD/CAM Material

Purpose: Evaluate the effect of food simulating liquids and thermocycling on miniflexural strength and surface micro-hardness of a resin nano-ceramic material (Lava Ultimate) compared to indirect laboratory composite resin material (Nexco Paste) and direct composite resin material (Filtek Z350 XT).Material and Methods: A total number of 180 samples were fabricated. The samples were divided equally into 3 groups (n=60). Group 1 (M1) samples were fabricated from the resin nano ceramic CAD/CAM blocks (Lava Ultimate), group 2 (M2) samples were farbricated form indirect micro-hybrid resin composite (Nexco Paste), while group 3 (M3) samples were fabricated from direct resin composite (Filtek Z350 XT). Thirty bars (12X2X2mm) from each material were fabricated to evaluate the mini flexural strength. Thirty disks (8X2mm) were fabricated from each material to evaluate thesurface micro-hardness. The samples of M1 groups were fabricated by cutting from the CAD/CAM block using low speed diamond disk while samples of M2 and M3 samples were fabricated using teflon mold. Each material samples were further subdivided into 6 subgroups; the first subgroup was not immersed into food simulating liquids nor thermocycled,4 subgroups samples were immersed into food simulating liquids (water, ethanol, heptane and citric acid) and the last subgroup samples were thermocycled. Mini flexural strength test was done using universal testing machine and surface hardness was done using Vickers hardness tester.Results: Lava Ultimate showed the significantly highest mini flexural strength and surface micro-hardness values before and after immersion into food simulating liquids and thermocycling compared to the two other tested materials. Conclusion: According to the results of the present study, Lava Ultimate showed better mini flexural strength and surface micro-hardness compared to the two othertested materials.

MP21-02 NOVEL QUANTITATIVE IMAGING ALGORITHMS DISTINGUISH LOCALIZED AND METASTATIC HIGH-GRADE PRIMARY PROSTATE CANCERS

INTRODUCTION AND OBJECTIVES: Prostate cancers (PC) associated with overt metastases at diagnosis (stage M1) or that progress to this stage are lethal. Although pathologic features of most M1 cases are indistinguishable from high-grade, non-metastatic PC (stage M0), profound disparities in outcome are apparent. More than 70% of M1 patients progress to castration-resistant prostate cancer (CRPC) and death within 5 years compared to 100% survival of highgrade M0 cases. Improved tools that detect features of lethal high-grade disease in prostate needle biopsies (PNBXs) will enable early identification of patients at greatest risk of metastatic progression. We have applied novel quantitative imaging (QI) technology and validated machine learning software tools to extract histomorphometric features from PNBX specimens that distinguish M1 and M0 cancers. This 00computer vision00 approach can be applied to routine diagnostic biopsies with the goal of detecting lethal PC as early as possible and improving patient stratification for entry into clinical trials. METHODS: We created a diverse, annotated biorepository with detailed clinical information corresponding to PNBX tissue from 427 patients with high-grade M0 or M1 PC. Retrospective analysis was used to assemble cohorts matched for age, race, and Gleason grade that were either M0 (n1⁄48) or M1 (n1⁄410). Archival PNBX slides stained with hematoxylin and eosin were quality checked and digitally scanned at 40X magnification. Fifteen image tiles were collected from each slide and two classifiers were constructed to assign each image tile to the M0 or M1 groups. QI analysis was used to investigate a set of features, including Fractal Dimensions (FD), Lacunarity (LA) [1st classifier], and Nuclear Features (NF) [2nd classifier] in M0 and M1 PC. RESULTS: Approximately 332 image tiles from the M0-RRP (n1⁄4122) and M1-ADT (n1⁄4210) cases were converted to nuclear masks. Using LA and FD tests, a trained classifier achieved 70% accuracy in distinguishing images from M1 and M0 cases, in which LA features were significantly different. We also identified 63 NFs differentially expressed in the M0 and M1 cases after random selection of 30% of nuclei and calculation of 1,500 NFs using partial least squares method. With this method, a classifier trained with the selected NFs to characterize nuclear intensity, texture, size, and shape achieved an accuracy of 75.5% in M0-RRP cases and 74.8% in M1-ADT cases. CONCLUSIONS: This innovative cohort of patients at the extremes of high-grade PC provides the opportunity to generate and test the performance of novel QI algorithms.

Stent Retriever Thrombectomy in Different Thrombus Locations of Anterior Cerebral Circulation.

Mechanical thrombectomy (MT) is a safe and efficient treatment for acute ischemic stroke in patients with proximal anterior occlusion and large penumbra. We evaluated the technical and clinical success of MT in relation to the location of the occlusion (internal carotid artery, M1 and M2 segments of the middle cerebral artery). We prospectively reviewed 130 patients of whom 105 met the inclusion criteria. Baseline clinical, procedural and imaging variables, technical outcome (TICI, thrombolysis in cerebral infarction), 24h imaging outcome and three-month clinical outcome (mRS, modified Rankin Scale) were recorded. Differences between the groups were studied with statistical tests according to the type of the variable. There were 37, 46 and 22 patients in the internal carotid artery (ICA), M1 and M2 groups, respectively. TICI 2b or 3 was achieved in 92 cases (88%) with a non-significant trend towards a better recanalization outcome in the ICA and M1 groups. Overall, 57 of the 105 patients (55%) experienced favorable clinical outcome (mRS≤2) with no significant differences between the groups. Excellent outcome (mRS≤1) was seen in 40 patients (39%) and there proportionally more patients with excellent outcome in the ICA and M1 groups (ICA: 44%, M1: 41%, M2: 23% of patients, p=0.22). There were no statistically significant differences in the technical or clinical outcomes between the different sites of occlusion (ICA, M1 or M2). There was a non-significant trend towards achieving excellent clinical outcome (3-month mRS≤1) more often and better recanalization results in the two more proximal locations.

391 How accurate is the PSA test? A prevalence study of disturbed PSA values in a tertiary referral hospital

INTRODUCTION AND OBJECTIVES: Prostate cancers (PC) associated with overt metastases at diagnosis (stage M1) or that progress to this stage are lethal. Although pathologic features of most M1 cases are indistinguishable from high-grade, non-metastatic PC (stage M0), profound disparities in outcome are apparent. More than 70% of M1 patients progress to castration-resistant prostate cancer (CRPC) and death within 5 years compared to 100% survival of highgrade M0 cases. Improved tools that detect features of lethal high-grade disease in prostate needle biopsies (PNBXs) will enable early identification of patients at greatest risk of metastatic progression. We have applied novel quantitative imaging (QI) technology and validated machine learning software tools to extract histomorphometric features from PNBX specimens that distinguish M1 and M0 cancers. This 00computer vision00 approach can be applied to routine diagnostic biopsies with the goal of detecting lethal PC as early as possible and improving patient stratification for entry into clinical trials. METHODS: We created a diverse, annotated biorepository with detailed clinical information corresponding to PNBX tissue from 427 patients with high-grade M0 or M1 PC. Retrospective analysis was used to assemble cohorts matched for age, race, and Gleason grade that were either M0 (n1⁄48) or M1 (n1⁄410). Archival PNBX slides stained with hematoxylin and eosin were quality checked and digitally scanned at 40X magnification. Fifteen image tiles were collected from each slide and two classifiers were constructed to assign each image tile to the M0 or M1 groups. QI analysis was used to investigate a set of features, including Fractal Dimensions (FD), Lacunarity (LA) [1st classifier], and Nuclear Features (NF) [2nd classifier] in M0 and M1 PC. RESULTS: Approximately 332 image tiles from the M0-RRP (n1⁄4122) and M1-ADT (n1⁄4210) cases were converted to nuclear masks. Using LA and FD tests, a trained classifier achieved 70% accuracy in distinguishing images from M1 and M0 cases, in which LA features were significantly different. We also identified 63 NFs differentially expressed in the M0 and M1 cases after random selection of 30% of nuclei and calculation of 1,500 NFs using partial least squares method. With this method, a classifier trained with the selected NFs to characterize nuclear intensity, texture, size, and shape achieved an accuracy of 75.5% in M0-RRP cases and 74.8% in M1-ADT cases. CONCLUSIONS: This innovative cohort of patients at the extremes of high-grade PC provides the opportunity to generate and test the performance of novel QI algorithms.

Primary implant stability in a bone model simulating clinical situations for the posterior maxilla: an in vitro study.

PurposeThe aim of this study was to determine the influence of anatomical conditions on primary stability in the models simulating posterior maxilla.MethodsPolyurethane blocks were designed to simulate monocortical (M) and bicortical (B) conditions. Each condition had four subgroups measuring 3 mm (M3, B3), 5 mm (M5, B5), 8 mm (M8, B8), and 12 mm (M12, B12) in residual bone height (RBH). After implant placement, the implant stability quotient (ISQ), Periotest value (PTV), insertion torque (IT), and reverse torque (RT) were measured. Two-factor ANOVA (two cortical conditions×four RBHs) and additional analyses for simple main effects were performed.ResultsA significant interaction between cortical condition and RBH was demonstrated for all methods measuring stability with two-factor ANOVA. In the analyses for simple main effects, ISQ and PTV were statistically higher in the bicortical groups than the corresponding monocortical groups, respectively. In the monocortical group, ISQ and PTV showed a statistically significant rise with increasing RBH. Measurements of IT and RT showed a similar tendency, measuring highest in the M3 group, followed by the M8, the M5, and the M12 groups. In the bicortical group, all variables showed a similar tendency, with different degrees of rise and decline. The B8 group showed the highest values, followed by the B12, the B5, and the B3 groups. The highest coefficient was demonstrated between ISQ and PTV.ConclusionsPrimary stability was enhanced by the presence of bicortex and increased RBH, which may be better demonstrated by ISQ and PTV than by IT and RT.

Advanced small cell carcinoma of the bladder: clinical characteristics, treatment patterns and outcomes in 960 patients and comparison with urothelial carcinoma.

To describe the clinical characteristics, treatment patterns and outcomes in advanced small cell bladder cancer (aSCBC) patients and compare to those with urothelial carcinoma (UC). Individuals in the National Cancer Data Base with a diagnosis of either nodal (TxN+M0) or distant metastatic (TxNxM1) disease were identified from 1998 to 2010. We assessed the relationships between stage, treatment modalities and survival in the aSCBC cohort and compared these to UC patients. In the 960 patient aSCBC cohort (62% M1), 50% received palliative therapy alone, 68% in M1 versus 21% in M0 groups (P<0.0001). Single modality local therapy (15%) and surgical (21%) or radiation-based (14%) multimodal therapy (MMT) were used in the other 50%. Cystectomy-based MMT was utilized in 45% of N+M0 versus 6.4% of NxM1 patients (P<0.0001). Median overall survival (OS) for aSCBC patients was 8.6months; 13.0months in N+M0 versus 5.3months in NxM1 patients (P<0.0001). Survival was similar between TxN1M0 and TxN2-3M0 patients (14.8months vs. 12.1months, P=0.15). Urothelial carcinoma patients (n=27,796, 45% M1) lived longer compared to aSCBC patients in the N+M0 group (17.3months vs. 13.0months, P=0.0007). There were not clinically significant differences in OS between UC and aSCBC patients in the M1 group. Advanced SCBC is a rare disease with a poor survival and palliative therapy is common, especially in M1 patients. In comparison to UC, the outcomes for aSCBC patients are worse in those with lymph node only involvement but similar in those with distant disease.

Clinical Significance of Soluble Interleukin-2 Receptor in Patients with Acute Leukemia

Objective: Investigate the expression level and clinical significance of serum soluble interleukin-2 receptor (sIL-2R, sCD25) in patients with acute leukemia.Methods: Serum sCD25 level were measured using enzyme linked immunosorbent assays (ELISA) in 97 acute leukemia patients and 10 healthy contrlols. Clinical and laboratory features, including bone marrow cellularity, white blood cell count (WBC), platelets (PLT), lactate dehydrogenase (LDH), serum ferritin (SF), erythrocyte sedimentation rate (ESR), as well as overall survival (OS) data were collected.Results: (1) Serum sCD25 level of the newly diagnosed leukemia group was significantly higher than that of the control group (P<0.0001). (2) Among the newly diagnosed AML patients, serum sCD25 level of the M3 group was significantly lower than that of the M2 or non-M2/M3 group (P<0.05). In addition, serum sCD25 level of the low/intermediate risk (AML) or standard risk (ALL) group was lower than that of the high risk group (P<0.05). (3) Serum sCD25 level of the complete remission (CR) group was significantly lower than that of the newly diagnosed group (P<0.002). However, no significant decrease was found in serum sCD25 level of the relapsed/refractory group compared to that of the newly diagnosed group. (4) Serum sCD25 level in newly diagnosed patients was positively correlated with peripheral WBC, LDH and SF. (5) Furthermore, although OS of the low sCD25 level group (sCD25<2000pg/ml) was not significantly different compared to the intermediate sCD25 level group (2000≤sCD25≤4000pg/ml) (P =0.532), both that of the low or intermediate sCD25 level group were significantly superior to that of the high sCD25 level group (sCD25>4000pg/ml) (P<0.05).Conclusion: Serum sCD25 levels have important clinical significance in evaluating disease activity, treatment outcomes and prognosis in patients with acute leukemia. DisclosuresNo relevant conflicts of interest to declare.

Assessment of the genetic diversity among oily spot (Xanthomonas axonopodis pv. punicae) pathogen of pomegranate by randomly amplified polymorphic DNA analysis

Pomegranate (Punica granatum L.) is an important fruit crop of India and other subtropical countries. Bacterial blight caused by Xanthomonas axonopodis pv. Punicae is becoming a major threat in Maharashtra as well as other states of India. It causes yield losses up to the extent of 80 – 90 %. This study aims to the collection of 7 strains (X. axonopodis) and utilized for assessment of genetic diversity by using RAPD markers. Whereas 7 strains of X. axonopodis were differentiated and distinguished into seven major region representing Malegaon, Nampur, Satana, Khakurdi, Ramnagar, Rahuri and Nashik region. However the genetic similarity within 7strains of X. axonopodis was ranged between 72.72-100 %. Similarly the genetic relationship of strains X. axonopodis was also established and showed 72.72 %, 72.72 %, 72.72 % 92.30%, 94.11% and 100 % similarity with region of Malegaon, Nampur, Satana, Khakurdi, Ramnagar, Rahuri and Nashik region. Average polymorphism in strains of X. axanopodis based on RAPD analysis was 84.095 %. The combine data analysis by using UPGMA method also revealed the two distinct groups representing seven strains of X. axonopodis and in first group M1 and second group R4 and subgroup RH6, N2, NS7, S3, K5, these genotypes were present respectively. Considering predominance and economic loss caused by X. axonopodis pv. punicae in pomegranate, it is an essential to undertake preliminary work on characterization of this pathogen at the molecular level.

Abstract LB-C06: Early prognostic significance of circulating laminin γ2-chain fragment in non-small-cell lung cancer

Abstract Background: Laminin γ2-chain (Ln-γ2), a distinctive subunit of heterotrimeric laminin-332, is frequently up-regulated in various types of carcinomas, and is of great importance in the biological processes including cell migration and tumor invasion. Despite of this, the status of circulating Ln-γ2 fragment in lung cancer patients is still uncertain. Methods: In this study, serum samples from 538 all-stage (stage I-IV) patients of non-small-cell lung cancer (NSCLC) and 94 age-matched normal volunteers were determined by enzyme-linked immunosorbent assay. Data were statistically analyzed in combination with clinicopathological information. Results: Compared to the normal controls, serum Ln-γ2 concentration is drastically increased in NSCLC patients (P &amp;lt; 0.001), even in early cases of stage I patients (P &amp;lt; 0.001). Furthermore, our data suggested that serum Ln-γ2 level was in close correlation to male gender (P &amp;lt; 0.001) and smoking status (P &amp;lt; 0.001) with a higher positive rate relative to each counterpart, but was not significant between adenocarcinoma and squamous cell carcinoma histologies (P = 0.879). We also found that circulating Ln-γ2 could reflect the progression of lung cancer with higher serum levels or positive rates in higher tumor-node-metastasis (TNM) stages. Survival analysis on 370 eligible patients who underwent a follow-up examination up to 4 years indicated that patients of serum Ln-γ2 positive group survived markedly shorter compared with those in the negative group (P = 0.028), and it was especially the case for clinical stage I (N = 72, P &amp;lt; 0.001) and stage T1 (N = 67, P = 0.001), even for stage N0 patients (N = 148, P = 0.038), which all represent groups of early cases. As for the patients of advanced stages, however, it was not the case that the overall survival rates between Ln-γ2 positive and negative patients were not significantly different among clinical stages II-IV (P = 0.830), stages T2-4 (P = 0.575), stages N1-3 (P = 0.669), and stage M1 (P = 0.849) groups, respectively. Subsequently, Cox regression analysis was performed to define serum Ln-γ2 as an independent prognostic indicator in the all-stage NSCLC cases (N = 370, univariate, P = 0.035; multivariate, P = 0.007). Worthy of note, however, in the multivariate analysis on those more advanced cases (stage II-IV), no statistical significance was observed on the serum levels of Ln-γ2 (N = 298, P = 0.234). Conclusion: In summary, our study suggests circulating Ln-γ2 to be a promising diagnostic biomarker for early-stage NSCLC and an effective indicator of tumor progression. It is proposed that circulating Ln-γ2 might be important and applicable for the prognosis of early-stage NSCLC patients, rather than that of advanced cases. Citation Format: Yu Teng, Li Ma, Xiaoting Zhao, Lina Zhang, Meng Gu, Yue Wang, Wentao Yue. Early prognostic significance of circulating laminin γ2-chain fragment in non-small-cell lung cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-C06.

Repetitive deep transcranial magnetic stimulation for motor symptoms in Parkinson's disease: A feasibility study

ObjectivesRepetitive transcranial magnetic stimulation (rTMS), using standard coils, provided modest symptomatic benefits in patients with Parkinson's disease (PD). In our previous exploratory studies, using the newly developed Hesed coil (providing deeper rTMS; rDTMS) high frequency (HF), excitatory rDTMS over the primary motor cortex (M1), did not achieve sufficient beneficial effect for PD symptoms, while low frequency (LF) inhibitory stimulation, was mildly beneficial.To further investigate the optimal rDTMS stimulation parameters for PD patients, and to assess whether there is an added value for dual stimulation, consisting of HF rDTMS over the prefrontal cortex (PFC) along with LF M1 rDTMS. The rational for the selection of the current stimulation parameters and sites lies on the previous studies that demonstrated an inhibitory effect of 1Hz rTMS on the increased cortical activity in PD as well as dopamine release by PFC stimulation. Patients and methodsAn open comparative active study of one month duration (12 sessions) of LF rDTMS over M1 alone (n=9) or combined with HF PFC rDTMS (M1-PFC, n=10). Outcome measures included the total and motor Unified Parkinson's Disease Rating Scale scores (T-UPDRS and M-UPDRS) and other variables, were collected at baseline and on days 30 and 60. ResultsFor the M1+PFC group, T-UPDRS score improved from baseline to day 30, by 15% (median: 52 points, decreased to 44, p=0.02, effect size: 0.51) and M-UPDRS score improved by 24% (median: 37 points decreased to 28, p=0.04, effect size: 0.47). The corresponding results for the M1 group were insignificant. Additionally, the between groups comparison, was insignificant. ConclusionrDTMS, consisting of M1 excitation with PFC inhibition improved PD motor symptoms but was not significantly superior to M1 rDTMS alone. rDTMS stimulation protocols for M1 should be further evaluated in larger scale controlled studies.

Intravenous tissue plasminogen activator before endovascular treatment increases symptomatic intracranial hemorrhage in patients with occlusion of the middle cerebral artery second division: subanalysis of the RESCUE-Japan Registry.

No previous study has investigated the relationship between intravenous tissue plasminogen activator (IV t-PA) and intracranial hemorrhage (ICH) according to the location of vessel occlusion. The aim of the present study was to investigate the relationship between preprocedural IV t-PA and endovascular treatment (EVT) and ICH according to the location of occlusion using data from the nationwide prospective registry of acute cerebral large vessel occlusion (LVO), the RESCUE-Japan Registry. Among 1442 patients with acute LVO enrolled in the registry, we examined 410 patients who received EVT. Patients were divided into the following four groups according to the location of occlusion: the internal carotid artery (ICA), middle cerebral artery first division (M1), middle cerebral artery second division (M2), and vertebral artery (VA)/basilar artery (BA) groups. A total of 399 patients in whom the occlusion was located in these vessels were finally included. Any ICH (aICH) was identified in 127 (30.9%) patients, and symptomatic ICH (sICH) was identified in 20 (4.9%). Preprocedural IV t-PA did not increase the incidence of aICH in any group and tended to increase the incidence of sICH in only the M2 group. In multivariate analysis of the M2 group, IV t-PA was an independent risk factor for sICH. Preprocedural IV t-PA did not increase the incidence of ICH in total, but could increase the incidence of sICH in those with M2 occlusion. IV t-PA before EVT may be an independent risk factor for sICH in patients with M2 occlusion.

Effects of fluoxetine and escitalopram on depressive-like behavior and hippocampal BDNF gene expression in adult rats

Objective To investigate the effects of different duration of fluoxetine and escitalopram administration on depressive-like behavior and hippocampal BDNF expression in adult rats. Methods Ninety-six SD rats were randomly divided into twelve groups: (1)M1 group: normal control for one week, (2)M2 group: CUMS+ saline for one week, (3)M3 group: CUMS+ fluoxetine for one week, (4) M4 group: CUMS+ escitalopram for one week, (5)M5 group: normal control for two weeks, (6)M6 group: CUMS+ saline for two weeks, (7)M7 group: CUMS+ fluoxetine for two weeks, (8)M8 group: CUMS+ escitalopram for two weeks, (9)M9 group: normal control for three weeks, (10)M10 group: CUMS+ saline for three weeks, (11)M11 group: CUMS+ fluoxetine for three weeks, (12) M8 group: CUMS+ escitalopram for three weeks. After CUMS procedures, rats in M2 group, M6 group and M10 group were injected with saline, M3 group, M7 group and M11 group were injected with fluoxetine, and rats in M4 group, M8 group, M12 group were injected with escitalopram. After one week of intervention, the open-field test and 1% sucrose preference test were performed to evaluate depression-like behaviors in rats of M1 group, M2 group, M3 group and M4 group. After behavior test, rats were sacrificed and the hippocampi were isolated. The expression of BDNFmRNA was detected by using real-time quantitative PCR. After two weeks of intervention, rats in M5 group, M6 group, M7 group and M8 group underwent the same behavioral. After three weeks of intervention, rats in M9 group, M10 group, M11 group and M12 group underwent the same behavioral test. Results In the open-field test, total distance travelled in 10 minutes was significant difference among the following groups: M1 group ((3925.70±322.32) cm) vs M3 group ((1841.85±786.33) cm), M6 group ((1820.31±296.00) cm) vs M8 group ((4002.72±1447.19) cm), M10 ((1961.66±919.16) cm) group vs M11 group ((3741.72±1064.46 ) cm), M10 group ((1961.66±919.16) cm) vs M12 group ((4280.43±1187.05) cm). In the 1% sucrose preference test, the difference of sucrose preference consumption was statistically significant (P<0.05) among the following groups: M2 group ((56.23±7.49)%) vs M4 group ((70.55±4.96)%), M6 group ((60.22±8.81)%) vs M8 group ((75.08±4.15)%), M10 group ((60.26±7.20)%) vs M11 group ((73.88±7.73)%), M10 group ((60.26±7.20)%) vs M12 group ((73.52±7.58)%). The expression level of BDNF was significant difference among these groups: M2 group (0.66±0.14) vs M4 group (1.15±0.20), M10 group (0.90±0.15) vs M11 group (1.22±0.09), M10 group (0.90±0.15) vs M12 group (1.48±0.20). Conclusion Both of fluoxetine and escitalopram can improve depression-like behaviors in rats and significantly increase the expression of the hippocampal BDNFmRNA. Compared with fluoxetine, escitalopram has a shorter onset time in the treatment of depression.It may be related with a rapid increase of the expression of BDNF mRNA. Key words: Fluoxetine; Escitalopram; Depression; Cyclic adenosine monophosphate response element binding protein; Brain derived neurotrophic factor

Antibacterial Surgical Silk Sutures Using a High-Performance Slow-Release Carrier Coating System

Sutures are a vital part for surgical operation, and suture-associated surgical site infections are an important issue of postoperative care. Antibacterial sutures have been proved to reduce challenging complications caused by bacterial infections. In recent decades, triclosan-free sutures have been on their way to commercialization. Alternative antibacterial substances are becoming relevant to processing surgical suture materials. Most of the antibacterial substances are loaded directly on sutures by dipping or coating methods. The aim of this study was to optimize novel antibacterial braided silk sutures based on levofloxacin hydrochloride and poly(ε-caprolactone) by two different processing sequences, to achieve suture materials with slow-release antibacterial efficacy and ideal physical and handling properties. Silk strands were processed into sutures on a circular braiding machine, and antibacterial treatment was introduced alternatively before or after braiding by two-dipping-two-rolling method (M1 group and M2 group). The antibacterial activity and durability against Staphylococcus aureus and Escherichia coli were tested. Drug release profiles were measured in phosphate buffer with different pH values, and release kinetics model was built to analyze the sustained drug release mechanism between the interface of biomaterials and the in vitro aqueous environment. Knot-pull tensile strength, thread-to-thread friction, and bending stiffness were determined to evaluate physical and handling properties of sutures. All coated sutures showed continuous antibacterial efficacy and slow drug release features for more than 5 days. Besides, treated sutures fulfilled U.S. Pharmacopoeia required knot-pull tensile strength. The thread-to-thread friction and bending stiffness for the M1 group changed slightly when compared with those of uncoated ones. However, physical and handling characteristics of the M2 group tend to approach those of monofilament ones. The novel suture showed acceptable in vitro cytotoxicity according to ISO 10993-5. Generally speaking, all coated sutures show potential in acting as antibacterial suture materials, and M1 group is proved to have a higher prospect for clinical applications.

Chronic administration of methamphetamine promotes atherosclerosis formation in ApoE−/− knockout mice fed normal diet

ObjectiveChronic methamphetamine (METH) abuse could induce neurotoxicity due to reactive oxygen species generation and sympathetic activation. Both factors are associated with atherosclerosis, so we tested the hypothesis that chronic METH administration might also promote atherosclerosis formation in Apo E−/− knockout mice fed normal diet. Methods and ResultsMale ApoE−/− mice (6 weeks-old) were treated with saline (NS) or METH [4 mg/kg/day (M4) or 8 mg/kg/day (M8) through intraperitoneal injection] for 24 weeks. Atherosclerotic lesion area on oil red O stained en face aorta was dose-dependently increased in M4 and M8 groups compared to NS group. Percentage of atherosclerotic lesion area was significantly higher in M8 group compared to NS and M4 groups. Plasma CRP was increased and inflammatory cytokine (ICAM-1, VCAM-1, TNF-α, and INF-γ) expression on aortic root was upregulated in METH groups compared to NS group. Neuropeptide Y (NPY) protein and mRNA expressions in aortic root and myocardial tissue were determined by Western blot and real time PCR, which were significantly upregulated in M4 and M8 groups. Moreover, mRNA expressions of NPY1R, NPY2R and NPY5R in aortic and myocardial tissue were also significantly upregulated in M4 and M8 groups. Raw264.7 cells were treated with NPY, NPY receptor antagonists, METH (10 μM or 100 μM) with or without lipopolysaccharide (LPS), and the expressions of TNF-α, CRP, MCP-1 and reactive oxygen species (ROS) production were significantly increased in METH and LPS + METH groups compared to control and LPS groups. Co-treatment with NPY1R antagonist decreased the expressions of TNF-α, CRP and MCP-1 in NPY and METH treated cells. ConclusionsChronic METH administration can promote inflammation and atherosclerotic plague formation in ApoE−/− mice fed normal chow. NPY might be involved in the pathogenesis of METH-induced atherogenic effects through NPY Y1 receptor pathway.

The influence of distant metastases on serum TSH elevation after L-T4 withdrawal in differentiated thyroid cancer

Objective To investigate the influence of distant metastases on the increase rate (vx) of serum TSH and its change rate(Ra) in patients with DTC after thyroid hormone withdrawal (THW). Methods Three times or more serum TSH measurements were performed before and after THW in 97 patients (38 males, 59 females) who had underwent successful 131I ablation from January 2014 to July 2014. v1 (early period vx), v2 (later period vx) and change rate of v1 and v2 (Ra) were calculated and compared between M0 group (without distant metastases, n=67) and M1 group (with distant metastases, n=30). Two-sample t test and rank-sum test were used for statistical analysis. Results v1 in males was significantly higher than that in females ((3.58±2.13) vs (2.63±1.54) mU·L-1·d-1; t=2.549, P=0.012). v2 in M0 group was significantly higher than that in M1 group ((7.67±3.66) vs (3.68±4.33) mU·L-1·d-1; t=3.613, P=0.001). The difference of Ra between M0 group and M1 group was statistically significant(z=-4.17, P<0.05). Conclusions Distant metastases may affect the increase rate and its change pattern of serum TSH after THW. Serum TSH showed a slow elevation over time or even decline in patients with distant metastasis. Meanwhile TSH increased much higher over the THW time in most of the patients in M0 group. It was suggested that attention should be paid to the variation of serum TSH in DTC patients with distant metastases to avoid decrease of TSH during longer THW. Key words: Thyroid neoplasms; Neoplasm metastasis; Surgery, operative; Radiotherapy; Iodine radioisotopes; Thyroxine; Thyrotropin

A molecular trigger for intercontinental epidemics of group A Streptococcus.

The identification of the molecular events responsible for strain emergence, enhanced virulence, and epidemicity has been a long-pursued goal in infectious diseases research. A recent analysis of 3,615 genomes of serotype M1 group A Streptococcus strains (the so-called "flesh-eating" bacterium) identified a recombination event that coincides with the global M1 pandemic beginning in the early 1980s. Here, we have shown that the allelic variation that results from this recombination event, which replaces the chromosomal region encoding secreted NADase and streptolysin O, is the key driver of increased toxin production and enhanced infection severity of the M1 pandemic strains. Using isoallelic mutant strains, we found that 3 polymorphisms in this toxin gene region increase resistance to killing by human polymorphonuclear leukocytes, increase bacterial proliferation, and increase virulence in animal models of pharyngitis and necrotizing fasciitis. Genome sequencing of an additional 1,125 streptococcal strains and virulence studies revealed that a highly similar recombinational replacement event underlies an ongoing intercontinental epidemic of serotype M89 group A Streptococcus infections. By identifying the molecular changes that enhance upper respiratory tract fitness, increased resistance to innate immunity, and increased tissue destruction, we describe a mechanism that underpins epidemic streptococcal infections, which have affected many millions of people.

Dynamical masses of a nova-like variable on the edge of the period gap

We present the first dynamical determination of the binary parameters of an eclipsing SW Sextantis star in the 3–4 h orbital period range during a low state. We obtained time-resolved optical spectroscopy and photometry of HS 0220+0603 during its 2004–2005 low-brightness state, as revealed in the combined Small & Moderate Aperture Research Telescope System, IAC80 and M1 Group long-term optical light curve. The optical spectra taken during primary eclipse reveal a secondary star spectral type of M5.5 ± 0.5 as derived from molecular band-head indices. The spectra also provide the first detection of a DAB white dwarf in a cataclysmic variable. By modelling its optical spectrum we estimate a white dwarf temperature of 30 000 ± 5000 K. By combining the results of modelling the white dwarf eclipse from ULTRACAM light curves with those obtained by simultaneously fitting the emission- and absorption-line radial velocity curves and I-band ellipsoidal light curves, we measure the stellar masses to be M1 = 0.87 ± 0.09 M⊙ and M2 = 0.47 ± 0.05 M⊙ for the white dwarf and the M dwarf, respectively, and an inclination of the orbital plane of i ≈ 79°. A radius of 0.0103 ± 0.0007 R⊙ is obtained for the white dwarf. The secondary star in HS 0220+0603 is likely too cool and undersized for its mass.

Gonado-hypophyseal lesions and reproductive hormonal changes in Brucella melitensis-infected mice and its lipopolysaccharides (LPSs)

Gonado-hypophyseal lesions and reproductive hormonal changes in Brucella melitensis-infected mice and its lipopolysaccharide (LPS) were investigated. Forty-eight mice (24 males and 24 females) were used as infection models in this study, and they were divided into three equal separate groups of eight mice based on their sex: M1, M2, and M3 and F1, F2, and F3 (M = Male, F = Female). Groups M1 and F1 were orally inoculated with sterile phosphate-buffered saline (PBS) and served as the negative control. Groups M2 and F2 were orally inoculated with 0.4 ml of 109 colony-forming units (cfu) of B. melitensis, while groups M3 and F3 were orally inoculated with 0.4 ml of LPSs from 109 cfu of B. melitensis. All the groups were observed for 10 days for changes in clinical signs or signs of mortality and then euthanized. Whole blood was collected via cardiac puncture, while tissues were fixed in 10 % formalin for histopathological processing. Histopathological lesions in the male and female reproductive tracts ranged from mild to moderate degenerative, inflammatory, and necrotic lesions. These changes were moderate in M2 than in M3 in males and in F3 than in F2 groups in females. Lesions in the pituitary gland ranged from mild to moderate inflammation and necrosis with astrogliosis. F2 and M2 groups had more lesion distribution in the pituitary gland than F3 and M3 groups. There was a 13 % decline in progesterone concentration in F2 and a 44 % decline in F3. Estradiol level declined by 33 % in F2 and slightly increased by 4.2 % in F3. Progesterone-estrogen ratio (P/E) increased by 31 % in F2 and declined by 46 % in F3. Testosterone concentration increased by 74 % in M2 and decreased by 56 % in M3. The study showed that oral administration of B. melitensis affects the pituitary gland and may alter the hypothalamic-pituitary-gonadal axis.

Bone Scan Index predicts outcome in patients with metastatic hormone-sensitive prostate cancer.

To evaluate the Bone Scan Index (BSI) for prediction of castration resistance and prostate cancer-specific survival (PCSS). In this retrospective study, we used novel computer-assisted software for automated detection/quantification of bone metastases by BSI. Patients with prostate cancer are M-staged by whole-body bone scintigraphy (WBS) and categorised as M0 or M1. Within the M1 group, there is a wide range of clinical outcomes. The BSI was introduced a decade ago providing quantification of bone metastases by estimating the percentage of bone involvement. Being too time consuming, it never gained widespread clinical use. In all, 88 patients with prostate cancer awaiting initiation of androgen-deprivation therapy due to metastases were included. WBS was performed using a two-headed γ-camera. BSI was obtained using the automated platform EXINI bone (EXINI Diagnostics AB, Lund, Sweden). In Cox proportional hazard models, time to castration-resistant prostate cancer (CRPC) and PCSS were modelled as the dependent variables, whereas prostate-specific antigen (PSA) level, Gleason score and BSI were used as explanatory factors. For Kaplan-Meier estimates, BSI groups were dichotomously split into: BSI <1 and BSI ≥1. Discrimination between prognostic models was explored using the concordance index (C-index). The mean (range) age of the patients was 72 (52-92) years, the median (range) PSA level was 73 (4-5 740) ng/mL, the mean (range) Gleason score was 7.7 (2-10), and the mean (range) BSI was 1.0 (0-9.2). During a mean (range) follow-up of 26 (8-49) months, 48 patients became castration resistant and 15 had died; most (13) from prostate cancer. In multivariate analysis including PSA level, Gleason score and BSI, only prediction by BSI was statistically significant. This was true both for time to CRPC (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.22-1.74; C-index increase from 0.49 to 0.69) and for PCSS (HR 1.34, 95% CI 1.07-1.67; C-index increase from 0.76 to 0.95). BSI obtained using a novel automated computer-assisted algorithm appears to be a useful predictor of outcome for time to CRPC and PCSS in patients with hormone-sensitive metastatic prostate cancer.

Serotype M3 and M28 Group A Streptococci Have Distinct Capacities to Evade Neutrophil and TNF-α Responses and to Invade Soft Tissues.

The M3 Serotype of Group A Streptococcus (GAS) is one of the three most frequent serotypes associated with severe invasive GAS infections, such as necrotizing fasciitis, in the United States and other industrialized countries. The basis for this association and hypervirulence of invasive serotype M3 GAS is not fully understood. In this study, the sequenced serotype M3 strain, MGAS315, and serotype M28 strain, MGAS6180, were characterized in parallel to determine whether contemporary M3 GAS has a higher capacity to invade soft tissues than M28 GAS. In subcutaneous infection, MGAS315 invaded almost the whole skin, inhibited neutrophil recruitment and TNF-α production, and was lethal in subcutaneous infection of mice, whereas MGAS6180 did not invade skin, induced robust neutrophil infiltration and TNF-α production, and failed to kill mice. In contrast to MGAS6180, MGAS315 had covS G1370T mutation. Either replacement of the covS 1370T gene with wild-type covS in MGAS315 chromosome or in trans expression of wild-type covS in MGAS315 reduced expression of CovRS-controlled virulence genes hasA, spyCEP, and sse by >10 fold. MGAS315 covS wt lost the capacity to extensively invade skin and to inhibit neutrophil recruitment and had attenuated virulence, indicating that the covS G1370T mutation critically contribute to the hypervirulence of MGAS315. Under the background of functional CovRS, MGAS315 covS wt still caused greater lesions than MGAS6180, and, consistently under the background of covS deletion, MGAS6180 ΔcovS caused smaller lesions than MGAS315 ΔcovS. Thus, contemporary invasive M3 GAS has a higher capacity to evade neutrophil and TNF-α responses and to invade soft tissue than M28 GAS and that this skin-invading capacity of M3 GAS is maximized by natural CovRS mutations. These findings enhance our understanding of the basis for the frequent association of M3 GAS with necrotizing fasciitis.