Risk Factors that Predict Levothyroxine Medication after Thyroid Lobectomy.

CONTEXT AND OBJECTIVE: The risk of needing lifelong thyroid hormone supplementation is an important factor affecting treatment decisions for both patients and clinicians ahead thyroid lobectomy. The purposes of this study were to assess the predictive factors of levothyroxine medication after thyroid lobectomy. METHODS: We retrospectively reviewed 252 patients who had undergone lobectomy for benign thyroid nodules between April 2009 and April 2017. We conducted two independent analyses: patients who started taking levothyroxine after surgery were compared with those who did not, and patients who did not need levothyroxine at last follow-up were compared with those who required continued treatment. We investigated the correlations of patient clinicopathological characteristics and levothyroxine medication after lobectomy. RESULTS: Ninety-eight patients started levothyroxine after surgery. Of these, 34 patients successfully ceased medication and 64 patients continued treatment as of their last follow-up. In multivariate analysis, older age and preoperative TSH ≥2.0mIU/L were associated with levothyroxine initiation after surgery. In terms of continuity of levothyroxine, both older age and TSH ≥ 3.0mIU/L showed a significant correlation with continuous medication. We created a risk-scoring system to predict likelihood of starting and maintaining levothyroxine using the two significant factors in each comparison. A risk score of 3 or more indicated an increased risk of starting levothyroxine (specificity = 81.8%; sensitivity = 48.0%). A risk score of 3 or more indicated increased risk of continuous medication, (specificity = 94.2%; sensitivity = 35.9%). CONCLUSIONS: Greater age and higher preoperative TSH levels correlated with initiation and continuity of levothyroxine medication after lobectomy.

In vivo time-sequential histological study focused on melanocytes: suggestion of golden time for intervention to prevent post-laser pigmentary changes.

BACKGROUND: Post-inflammatory pigmentary changes after laser treatments are challenging adverse effect. OBJECTIVE: To suggest an ideal time period with regard to intervention to prevent post-laser pigmentary changes, an in vivo time-sequential histological study focused on melanocytes was performed. METHODS: The back skin of four volunteers was irradiated with Q-switched alexandrite laser (QSAL). In one subject (subject 4), topical corticosteroid was applied onto the irradiated skin from the time of irradiation to day 28. In all subjects, time-sequential skin biopsies were performed at baseline, an immediate time after irradiation, day 2, day 7, and day 28. Histological and immunohistochemical analyses were conducted. RESULTS: Q-switched alexandrite laser led to the successful removal of pigments and most melanocytes from the epidermis in all subjects. At day 28, there was increased epidermal pigmentation in the skin of the subjects 1-3. It was noted that numerous activated melanocytes appeared on day 7, continued to be observed until day 28. However, in the subject 4, the melanocyte activation and post-laser pigmentary changes were not observed. CONCLUSION: In regard to intervene melanocyte activation, at least 1 week after laser treatment is suggested as a 'golden' time period to prevent pigmentary changes.

Cytochalasin B inhibits the proliferation of human glioma U251 cells through cell cycle arrest and apoptosis.

Cytochalasin B (CB) is known to inhibit a number of cancer types, but its effects on gliomas are unknown. We examined the in vitro effects of CB on the proliferation of human glioma U251 cells, as well as determined its mechanism of action. Cell proliferation was determined using CCK-8. The effect of CB on U251 cell morphology was observed under a transmission electron microscope. Cell cycle distribution was assessed using propidium iodine and Giemsa staining, and cell apoptosis was determined by annexin V-fluorescein isothiocyanate/propidium iodide. Cell cycle-related proteins were determined by Western blot. CB effectively inhibited U251 cell proliferation in a dose- and time-dependent manner. The 24, 48, 72, and 96 h IC50 values were 6.41 x 10(-2), 9.76 x 10(-4), 2.57 x 10(-5), and 2.08 x 10(-5) M, respectively. CB increased the proportion of cells in the G2/M phase in a dose-dependent manner, thus increasing the mitotic index and decreasing cdc2 and cyclin B1 protein levels. CB induced morphological changes in the cytoskeleton. Additionally, 10(-5) M CB induced apoptosis in 23.4 ± 0.5% of U251 cells (P < 0.05 vs control group). Caspase-3, -8, and -9 activities were increased after CB treatment. CB inhibited U251 glioma cell proliferation by damaging the microfilament structure. CB also induced glioma cell apoptosis, suggesting that it may be an effective therapeutic agent against gliomas.

Factors influencing medical student attrition and their implications in a large multi-center randomized education trial.

Participant attrition may be a significant threat to the generalizability of the results of educational research studies if participants who do not persist in a study differ from those who do in ways that can affect the experimental outcomes. A multi-center trial of the efficacy of different computer-based instructional strategies gave us the opportunity to observe institutional and student factors linked to attrition from a study and the ways in which they altered the participation profile. The data is from a randomized controlled trial conducted at seven US medical schools investigating the educational impact of different instructional designs for computer-based learning modules for surgical clerks. All students undertaking their surgical clerkships at the participating schools were invited participate and those that consented were asked to complete five study measures during their surgery clerkship. Variations in study attrition rates were explored by institution and by participants' self-regulation, self-efficacy, perception of task value, and mastery goal orientation measured on entry to the study. Of the 1,363 invited participants 995 (73 %) consented to participate and provided baseline data. There was a significant drop in the rate of participation at each of the five study milestones with 902 (94 %) completing at least one of two module post-test, 799 (61 %) both module post-tests, 539 (36 %) the mid-rotation evaluation and 252 (25 %) the final evaluation. Attrition varied between institutions on survival analysis (p < 0.001). Small but statistically significant differences in self-regulation (p = 0.01), self-efficacy (p = 0.02) and task value (p = 0.04) were observed but not in mastery or performance goal orientation measures (p = NS). Study attrition was correlated with lower achievement on the National Board of Medical Examiners subject exam. The results of education trials should be interpreted with the understanding that students who persist may be somewhat more self-regulated, self-efficacious and higher achievers than their peers who drop out and as such do not represent the class as a whole.

Impact of MTHFR polymorphisms on methylation of MGMT in glioma patients from Northeast China with different folate levels.

Hypomethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter in glioma cells has been associated with temozolomide resistance. S-adenosylmethionine (SAM), which is produced during folate metabolism, is the main source of methyl groups during DNA methylation. As a key enzyme during folate metabolism, polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) may regulate folate end-products. We investigated the effect of typical polymorphisms of MTHFR (C677T and A1298C) on MGMT methylation based on different serum folate levels in patients with glioma from Northeast China. A total of 275 patients with glioma and 329 without malignant tumors were tested. Serum folate concentration was assayed by using the electrochemiluminescence immunoassay. MTHFR polymorphisms were detected by Taqman-Fluorescence quantitative polymerase chain reaction (PCR). Methylation-specific PCR was used to assess MGMT methylation. The constituent ratio of glioma patients below the serum folate biological reference value was significantly higher than that of the control population (P < 0.001). In patients with oligodendroglioma and glioblastoma, heterozygotes for the A1298C mutation were found in higher frequency than homozygotes or wild types (oligodendroglioma, P < 0.001; glioblastoma, P < 0.01). When grouped by the median or biological reference value of serum folate, only homozygotes for C677T with low levels of folate were significantly associated with decreased methylation of MGMT (median, P < 0.001; biological reference value, P = 0.036). These data suggest that, in combination with a negative folate balance in glioma patients, T/T genotypes in MTHFR C677T may be associated with MGMT demethylation.

Just enough, but not too much interactivity leads to better clinical skills performance after a computer assisted learning module.

BACKGROUND: Well-designed computer-assisted instruction (CAI) can potentially transform medical education. Yet little is known about whether specific design features such as direct manipulation of the content yield meaningful gains in clinical learning. We designed three versions of a multimedia module on the abdominal exam incorporating different types of interactivity. METHODS: As part of their physical diagnosis course, 162 second-year medical students were randomly assigned (1:1:1) to Watch, Click or Drag versions of the abdominal exam module. First, students' prior knowledge, spatial ability, and prior experience with abdominal exams were assessed. After using the module, students took a posttest; demonstrated the abdominal exam on a standardized patient; and wrote structured notes of their findings. RESULTS: Data from 143 students were analyzed. Baseline measures showed no differences among groups regarding prior knowledge, experience, or spatial ability. Overall there was no difference in knowledge across groups. However, physical exam scores were significantly higher for students in the Click group. CONCLUSIONS: A mid-range level of behavioral interactivity was associated with small to moderate improvements in performance of clinical skills. These improvements were likely mediated by enhanced engagement with the material, within the bounds of learners' cognitive capacity. These findings have implications for the design of CAI materials to teach procedural skills.

Biogeosciences Perspectives on Integrated, Coordinated, Open, Networked (ICON) Science.

This article is composed of three independent commentaries about the state of Integrated, Coordinated, Open, Networked (ICON) principles in the American Geophysical Union Biogeosciences section, and discussion on the opportunities and challenges of adopting them. Each commentary focuses on a different topic: (a) Global collaboration, technology transfer, and application (Section 2), (b) Community engagement, community science, education, and stakeholder involvement (Section 3), and (c) Field, experimental, remote sensing, and real-time data research and application (Section 4). We discuss needs and strategies for implementing ICON and outline short- and long-term goals. The inclusion of global data and international community engagement are key to tackling grand challenges in biogeosciences. Although recent technological advances and growing open-access information across the world have enabled global collaborations to some extent, several barriers, ranging from technical to organizational to cultural, have remained in advancing interoperability and tangible scientific progress in biogeosciences. Overcoming these hurdles is necessary to address pressing large-scale research questions and applications in the biogeosciences, where ICON principles are essential. Here, we list several opportunities for ICON, including coordinated experimentation and field observations across global sites, that are ripe for implementation in biogeosciences as a means to scientific advancements and social progress.

Field electron emission of ZnO nanowire pyramidal bundle arrays.

A facile hydrothermal method was adopted to in situ grow ZnO nanowire pyramidal bundle arrays on zinc substrates at low growth temperature without the assistance of catalysts and templates. The bundle arrays were shown to form by sticking of nanowires at their tips. Field electron emission characterization of nanowires bundle arrays revealed a very low turn-on electric field of about 2.3 V/microm and a threshold electric field (corresponding to the field electron emission current density of 10 mA/cm2) of 6.8 V/microm, which are comparable to those observed in carbon nanotube arrays. The bundle arrays also show pronounced long-term field electron emission stability at a high current density. In addition, the formation mechanism of the pyramidal bundled arrays and the origin of the peculiar field electron emission properties were discussed.

High-quality Graphenes via a facile quenching method for field-effect transistors.

Single- and few-layer graphene sheets with sizes up to 0.1 mm were fabricated by simply quenching hot graphite in an ammonium hydrogen carbonate aqueous solution. The identity and thickness of graphene sheets were characterized with transmission electron microscopy, atomic force microscopy, and Raman spectroscopy. In addition to its simplicity and scalability, the present synthesis can produce graphene sheets with excellent qualities in terms of sizes, purity, and crystal quality. The as-produced graphene sheets can be easily transferred to solid substrates for further processing. Field-effect transistors based on individual graphenes were fabricated and shown to have high ambipolar carrier mobilities.

Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer.

This prospective study was conducted with the Korean Cancer Study Group to evaluate the efficacy and safety of cetuximab combined with modified FOLFOX6 (mFOLFOX6) as first-line treatment in recurrent or metastatic gastric cancer and to identify potential predictive biomarkers. Patients received cetuximab 400 mg m(-2) at week 1 and 250 mg m(-2) weekly thereafter until disease progression. Oxaliplatin (100 mg m(-2)) and leucovorin (100 mg m(-2)) were administered as a 2-h infusion followed by a 46-h continuous infusion of 5-fluorouracil (2400 mg m(-2)) every 2 weeks for a maximum of 12 cycles. Biomarkers potentially associated with efficacy were analysed. Among 38 evaluable patients, confirmed response rate (RR) was 50.0% (95% CI 34.1-65.9). Median time-to-progression (TTP) was 5.5 months (95% CI 4.5-6.5) and overall survival (OS) 9.9 months. Eleven patients having tumour EGFR expression by immunohistochemistry with low serum EGF and TGF-alpha levels showed a 100% RR compared to 37.0% in the remaining 27 patients (P<0.001). Moreover, ligand level increased when disease progressed in seven out of eight patients with EGFR expression and low baseline ligand level. No patient exhibited EGFR amplification or K-ras mutations. Gastric cancer patients with EGFR expression and low ligand levels had better outcomes with cetuximab/mFOLFOX6 treatment.

High-aspect-ratio aluminum borate nanowire bundles supported by sucrose.

High-aspect-ratio and single-crystal aluminum borate (Al(18)B(4)O(33)) nanowire bundles with an ordered orientation were synthesized by using an innovative sucrose-assisted growth process. The process involves the dehydration and polycondensation of aluminum borate-sucrose solution to form a highly viscous precursor. The sucrose plays a crucial role in the growth of the nanowire bundles by supporting as a polymeric substrate and a type of adhesive template. Electron microscopy was used to characterize the high-aspect-ratio nanowire bundles. A possible growth mechanism for the nanowire bundles is proposed.

Clinical results of treatment of garden type 1 and 2 femoral neck fractures in patients over 70-year old.

INTRODUCTION: We retrospectively analyzed the clinical results of treatment of impacted or undisplaced femoral neck fractures (Garden types 1 and 2) by osteosynthesis in elderly patients >70-year old. MATERIALS AND METHODS: We retrospectively reviewed the radiological results of 52 patients who were followed up for at least 6 months from April 2002 to December 2008. The average age of the patients was 77.6 years (range 70-97 years), and 38 patients were females. The mean follow-up period was 11.7 months (range 6-19 months). Thirteen cases were Garden type 1 fractures, and 39 were Garden type 2 fractures. We assessed the relationships between the occurrence of complications and age, sex, Garden stage, bone mineral density (BMD), history of contralateral hip fracture, and any additional hip injury. RESULTS: Major complications occurred in 18 cases (34.6 %), including nonunion (8 cases), osteonecrosis (6 cases), stress fracture of the subtrochanter (2 cases), excessive pull-out of a screw (1 case), and deep infection (1 case). The development of complications was associated with Garden stage 2, BMD, and additional hip injury. However, other factors were not associated with complications. Reoperations were performed in 16 cases (30.1 %), and 2 of the patients died during follow-up. CONCLUSION: A relatively high rate of complications or reoperations developed after treatment of Garden 2 femoral neck fractures in senile patients >70 years of age with osteoporosis. Although internal fixation has been recommended in the literature for undisplaced femoral neck fractures, primary arthroplasty may be a better option for treatment of Garden type 2 fractures in elderly patients.

Cloning and characterization of tissue inhibitor of metalloproteinase-3 (TIMP-3) from shark, Scyliorhinus torazame.

We cloned the full-length cDNA encoding TIMP-3 from the cartilage of cloudy dogfish, Scyliorhinus torazame. The entire open reading frame was composed of 645 nucleotides and 214 residues including 12 conserved cysteines and asparagine-184, a putative site for N-linked sugars. It showed about 72% identity to those of other species based on the deduced amino acid sequence. The mRNA of shark TIMP-3 were expressed abundantly in brain and cartilage tissues. To investigate the roles of shark TIMP-3, an expression vector was constructed and transfected into HT1080 human fibrosarcoma cells. Overexpression of shark TIMP-3 reduced the activity of MMP-2 in gelatin zymography. Through human Alu PCR based CAM assay, we also confirmed that shark TIMP-3 transfected HT1080 cells had less intravasation effects.

Induction chemotherapy with idarubicin plus N4-behenoyl-1-beta-D-arabinofuranosylcytosine in acute myelogenous leukemia: a newly designed induction regimen--a prospective, cooperative multicenter study.

This report describes the results of induction chemotherapy with idarubicin (IDA) plus N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC), a newly designed induction regimen, in cases of previously untreated acute myelogenous leukemia (AML). The study was conducted by the Multicenter Clinical Study Group of the Korean Biologic Response Modifier Society (KBRMS). From March 1994 through January 1995, 40 patients were treated. The median age was 30 years (range, 15 months to 65 years), with a distribution according to the French-American-British (FAB) classification of one MO, nine MI, 15 M2, six M3, four M4, and five M5 patients. Remission induction therapy consisted of IDA 12 mg/m2 intravenously (i.v.) over 30 minutes daily on days 1 to 3, in combination with BH-AC 300 mg/m2 over 4 hours daily on days 1 to 7 (in patients aged 41 to 65 years, BH-AC dosage was decreased to 200 mg/m2/d). Complete remission (CR) was achieved in 30 patients (75%), 22 by the first induction therapy and eight by the second induction therapy. Ten patients (25%) failed to respond to therapy, six due to resistant disease and four due to death caused by aplasia. The time to CR was 30 days, the median granulocytopenic period was 19 days, and the thrombocytopenic period was 24 days. All nonhematologic side effects such as nausea, vomiting, mucositis, skin eruption, liver and cardiac dysfunction, and neurotoxicity, were transient and tolerable. These data indicate an efficacy comparable to that of other combinations of IDA (or other anthracyclines) with cytosine arabinoside (Ara-C) for remission induction in AML.

The pattern visual evoked potential and pattern electroretinogram in drusen-associated optic neuropathy.

Sixteen patients (29 eyes) with optic disc drusen were studied prospectively for clinical and electrophysiologic evidence of impaired optic nerve conduction. Abnormalities were detected in the following areas: visual acuity, eight (28%) of 29 eyes; kinetic visual field, 22 (76%) of 29 eyes; results of Farnsworth-Munsell 100-Hue test, 12 (41%) of 29 eyes; and flash visual evoked potential, 13 (54%) of 24 eyes. Simultaneous pattern visual evoked potentials and results of pattern electroretinograms were recorded. The P100 latency of the pattern visual evoked potential was prolonged in 41% of eyes. The P50 and N95 components of the pattern electroretinogram were also analyzed. The P50 amplitude was reduced in only four (17%) of 24 eyes. The most common abnormality was a reduction in amplitude or the absence of the N95 component in 19 (79%) of 24 eyes, reflecting ganglion cell dysfunction. The data support mounting evidence that the P50 and N95 components of the pattern electroretinogram have different retinal origins.

A prospective randomized study of Chop versus Chop plus alpha-2B interferon in patients with intermediate and high grade non-Hodgkin's lymphoma: the International Oncology Study Group NHL1 Study .

UNLABELLED: The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of alpha interferon thrice weekly maintenance therapy, has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL. BACKGROUND: The CHOP (Cyclophosphamide, Adriamycin. Vincristine, Prednisone) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade (IG/HG) non-Hodgkin's lymphoma (NHL). Alpha 2b interferon (INF) enhances response rates and improves survival in low-grade NHL. The International Oncology Study Group (IOSG) conducted a prospective randomized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL. The primary study aim was to compare the objective response rates in these patient cohorts. PATIENTS AND METHODS: Patients with a confirmed diagnosis of measurable NHL of International Working Formulation (IWF) groups D to H histology were randomized to receive CHOP alone or CHOP with 5Mu INF s.c. for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units (Mu) given three times per week subcutaneously for 52 weeks in those patients who responded to CHOP plus INF. RESULTS: The overall response rates were equivalent in both groups: CHOP alone (214 patients) 81% (complete 55%, partial 26%); CHOP plus INF (221 patients) 80% (complete 54%, partial 26%). At 36 months, the actuarial survival rate was equivalent in both groups. CONCLUSIONS: There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.

Scoliosis induced by anterior and posterior rhizotomy.

This paper presents the result and statistical analysis of an experiment in which selective anterior or posterior rhizotomy was carried out under microscopic surgery. The animals used for the experiment were 48 young rabbits, and they were divided into four groups. Group 1, which was used as control, was subjected to lower dorsal bilateral laminectomies with dural incision; Group II to laminectomies with three right posterior rhizotomies; Group III to laminectomies with three right anterior rhizotomies, and Group IV to laminectomies with three right anterior and posterior rhizotomies. Scoliosis was induced in Groups II, III, and IV. There was no significant statistical difference in the degree of curvatures among these three groups. The convexity of the curvature faced to the side of the divided roots. In Groups III and IV, scoliotic curvatures were obvious within 2 weeks, but there were no considerable changes thereafter. In Group II, the curves progressed slowly up to the 12th week. They were statistically significant at the fourth week and increased continuously thereafter. The histologic findings in Groups III and IV showed denervation atrophy of the paravertebral muscles at the apex of the curvature, but there was little or no muscle atrophy in Groups I and II. The experimental results indicate that scoliosis may be induced not only by anterior root paralysis but also by selective posterior root paralysis.

Radical-scavenging activities of citrus essential oils and their components: detection using 1,1-diphenyl-2-picrylhydrazyl.

Thirty-four kinds of citrus essential oils and their components were investigated for radical-scavenging activities by the HPLC method using 1,1-diphenyl-2-picrylhydrazyl (DPPH). To examine the oils' relative radical-scavenging activities compared with that of a standard antioxidant, Trolox was employed. All of the essential oils were found to have scavenging effects on DPPH in the range of 17. 7-64.0%. The radical-scavenging activities of 31 kinds of citrus essential oils were comparable with or stronger than that of Trolox (p < 0.05). The oils of Ichang lemon (64.0%, 172.2 mg of Trolox equiv/mL), Tahiti lime (63.2%, 170.2 mg of Trolox equiv/mL), and Eureka lemon (61.8%, 166.2 mg of Trolox equiv/mL) were stronger radical scavengers than other citrus oils. Citrus volatile components such as geraniol (87.7%, 235.9 mg of Trolox equiv/mL), terpinolene (87.4%, 235.2 mg of Trolox equiv/mL), and gamma-terpinene (84.7%, 227.9 mg of Trolox equiv/mL) showed marked scavenging activities on DPPH (p < 0.05).