Kikuchi-Fujimoto disease complicated by aseptic meningitis and hemophagocytosis successfully treated with intrathecal dexamethasone.
Kikuchi-Fujimoto disease (KFD) is thought to be a self-limited disease featuring fever and cervical lymphadenopathy; most cases having a favorable outcome. Severe disease and death are occasionally reported. Here we report a case of KFD complicated by hemophagocytosis and aseptic meningitis. The symptoms and laboratory parameters improved after systemic glucocorticoids, intravenous immunoglobulin and one dose of intrathecal dexamethasone. Clinicians should aware of this disease and make early diagnosis by lymph node biopsy to avoid over-treatment.


Comparison of effects of vanadium absorbed by Coprinus comatus with those of inorganic vanadium on bone in streptozotocin-diabetic rats.
The purpose of this study was to compare the effect of vanadium absorbed by Coprinus comatus (VACC) with inorganic vanadium (vanadium nitrate, IV) in preventing diabetes-related osteopenia in streptozotocin-diabetic rats. Sixty Wistar female rats used were divided into four groups: (1) normal rats (control), (2) diabetic rats, (3) diabetic rats treated with VACC, and (4) diabetic rats treated with vanadium nitrate. A standardized type 1-like diabetes model was induced by injection of streptozotocin. After the rats were treated orally with VACC and IV respectively, plasma glucose, body weights, micro-CT, biomechanical testing, and histomorphometry were examined. In addition, bone samples were obtained to evaluate the content of mineral substances in bones. Treatments were performed over a 12-week period. Both VACC and IV have a positive effect on plasma glucose and body weights of STZ-induced diabetic rats. However, treatment with IV only caused a 39.6 % decrease in glucose levels and a 14.6 % increase in body weights, whereas VACC decreased plasma glucose and increased body weights by up to 52.2 and 24.5 %, respectively. At the same time, VACC significantly improved trabecular microstructure and mechanical strength, while IV did not exhibit desirable such effects. Also, bone Ca and bone P were not significantly increased by IV. These results indicated that both VACC and IV have hypoglycemic activity on diabetic rats, while IV did not improve bone properties. In conclusion, this study suggests that VACC improves diabetes-related bone dysfunction, primarily by improving the diabetic states.


Hereditary ovalocytosis and reduced susceptibility to malaria in Papua New Guinea.
Ovalocytosis, an hereditary condition in which most erythrocytes are oval in shape, is a polymorphism that occurs in up to 20% or more of the population in Papua New Guinea and Malaysia. Due to the geographical correlation of the trait with endemic malaria, the possibility of a selective advantage in resistance to malaria has been raised. In a study of 202 individuals with greater than or equal to 50% oval red cells matched by age, sex and village of residence with controls having less than or equal to 30% oval cells, ovalocytic subjects had blood films negative for Plasmodium vivax (P = 0.009), for P. falciparum (P = 0.044), and for all species of malaria parasites (P = 0.013), more often than controls. Among individuals parasitaemic at any time there were no clear differences in density of parasitaemia. However, in children 2 to 4 years old, parasite densities of both species were lower in ovalocytic subjects than in controls (0.01 less than P less than 0.025). The differential susceptibility to malaria infection suggested by this study has implications for the evaluation of interventions, including possible future vaccine field trials, in populations where high-frequency ovalocytosis is present.


Counting Differently: Assessing Mathematics Achievement of Signing Deaf and Hard of Hearing Children Through a Unique Lens.
Limited studies exist that connect using signed language with mathematics performance of deaf and hard of hearing children. In the present study, the authors examined 257 participants and compared their results on the Northwest Evaluation Association: Measures of Academic Progress (NWEA MAP) to their results on an assessment of American Sign Language (ASL) skills. It was found that better ASL skills tended to result in better MAP performance. These results are moderated by factors such as age, gender, parental hearing status, and learning disability identification.


Performance of a new DNA probe for the detection of group B streptococcal colonization of the genital tract.
To test the performance characteristics of a new DNA probe designed for the rapid identification of heavy colonization of the genital tract with group B streptococci. Vaginal and combined vaginal-perianal samples were collected from 193 pregnant women and cultured on colistin-nalidixic acid agar plates. Bacterial growth was classified semiquantitatively. Specimens were also tested by a new DNA probe in two formats: a direct assay performed on the swabs soon after collection and an assay performed after the swabs were incubated for 24 hours in an enriched culture medium. The agar cultures were positive in 36 of 193 patients (18.6%, 95% confidence interval 13.2-24). Nineteen women were lightly colonized, and 17 were heavily colonized (at least 10(4) colonies/mL). The combined vaginal-perianal swabs yielded positive results more often than the vaginal swabs alone (26 versus 16, chi 2 = 24, P < .01). In its direct form, the assay had only 8.3% sensitivity in identifying colonized women. In heavily colonized women, the sensitivity of the assay increased slightly to 12%. After a 16-24-hour incubation, the sensitivity of the assay was 81%. The direct assay is insufficiently sensitive for clinical use. The delayed assay offers no advantage over standard cultures.


Crystal structure of Tk-subtilisin folded without propeptide: requirement of propeptide for acceleration of folding.
Tk-subtilisin (a subtilisin homologue from Thermococcus kodakaraensis) is matured from Pro-Tk-subtilisin upon autoprocessing and degradation of Tk-propeptide. To analyze the folding mechanism of Tk-subtilisin, the crystal structure of the active site mutant of Tk-subtilisin (S324A-subtilisin*), which was refolded in the presence of Ca2+ and absence of Tk-propeptide, was determined at 2.16A resolution. This structure is essentially the same as that of Tk-subtilisin matured from Pro-Tk-subtilisin. S324A-subtilisin* was refolded with a rate constant of 0.17 and 1.8min(-1) at 30 degrees C in the absence and presence of Tk-propeptide, respectively, indicating that Tk-subtilisin does not require Tk-propeptide for folding but requires it for acceleration of folding.


Medical student training in domestic violence: a comparison of students entering residency training in 1995 and 2001.
As domestic violence (DV) is frequently unrecognized by physicians, efforts to improve education on the topic have been undertaken. To assess changes in medical education about DV. Incoming residents from 1995 (N = 52) and 2001 (N = 43) were surveyed regarding education and attitudes about DV. The resident-reported emphasis on DV education increased significantly from 1995 to 2001. Hours devoted to the subject experienced no significant change. The likelihood they would ask female patients about DV and their competence in dealing with DV-specific situations experienced no significant improvement-both were rated below average. Although emphasis on medical education about DV has improved from 1995 to 2001, likelihood of screening and competence at dealing with DV has not improved. The content of undergraduate medical education about DV should be strengthened, and the educational process should continue during residency training.


Serum alkaline phosphatase level is positively associated with metabolic syndrome: A nationwide population-based study.
Serum alkaline phosphatase (ALP), a useful marker of hepatobiliary or bone disorder, has recently emerged as a biomarker of chronic low-grade inflammation and cardiometabolic disease. This study aimed to examine the association of serum ALP level with metabolic syndrome (MetS) in apparently healthy adults. A cross-sectional study was conducted to examine the relationship between serum ALP level and MetS in 7,101 men and 8,873 women aged 19 to 75 years using data from the 2008 to 2011 Korean National Health and Nutrition Examination Survey. The odds ratios (ORs) and 95% confidence intervals (CIs) for MetS were calculated using multiple logistic regression analyses across serum ALP quartiles (Q1: ≤190 U/L; Q2: 191-224 U/L; Q3: 225-263 U/L; and Q4: ≥264 U/L for men and Q1: ≤163 U/L; Q2: 164-201 U/L; Q3: 202-251 U/L; and Q4: ≥252 U/L for women). The mean values of most cardiometabolic variables, HOMA-IR, and leukocyte count gradually increased with serum ALP quartile. The prevalence of MetS significantly increased in accordance with serum ALP quartile. In comparison with those of individuals in the lowest quartile, the OR (95% CI) for MetS in the highest quartile was 1.32 (1.05-1.64) in men and 1.99 (1.42-3.81) in women after adjusting for age, cigarette smoking, alcohol intake, regular exercise, household income, education level, occupation, AST, ALT, and GGT levels. Serum ALP level was positively and independently associated with MetS in men and women.


Spectroscopic characterization of metal bound phytochelatin analogue (Glu-Cys)4-Gly.
The metal ion binding properties of a phytochelatin (PC) analogue, (Glu-Cys)4-Gly (named as EC4), have been studied by a divalent metal ion binding assay monitored by UV-visible spectroscopy, circular dichroism and NMR spectroscopy. Spectro- photometric titration with different divalent metal ions have revealed that the stiochoimetry of metal-bound EC4 was 1:1, and its metal binding affinities with different divalent metal ions in the order of Cd(II)>Cu(II)>Zn(II)>Pb(II)>Ni(II)>Co(II). UV-visible spectroscopic analysis of metal complexes indicated that four sulfur atoms in cysteine residues are attributable to ligand-to-metal charge transfer (LMCT) between divalent metal ions and EC4, and further confirmed by 1D H1 NMR study and Circular Dichroism. In addition, Circular Dichroism spectra of both free and metal-bound forms of EC4 revealed that metal coordination drives the nonapeptide chain to fold into a turned conformation. The comprehensive analysis of spectroscopic properties of the nonapeptide complexed with metal ions not only provides a fundamental description of the metal ion binding properties of PC analogue, but also shows a correlation between metal binding affinity of PC analogue and the induction activity of metal ions.


Visualization of stable ferritin complexes with palladium, rhodium and iridium nanoparticles detected by their catalytic activity in native polyacrylamide gels.
The reductive discoloration of azo dye, Congo red, catalyzed by noble metal nanoparticles was used to visualize protein-metal complexes in native polyacrylamide gels after counterstaining with Coomassie blue. This technique was used to characterize the synthesis of palladium, rhodium and iridium nanoparticles encapsulated in Pyrococcus furiosus ferritin.


Urodynamic investigation of valve bladder syndrome in children.
To investigate urodynamic manifestations and their relationship with the postoperative experience of children with valve bladder syndrome (VBS). Included were 16 children (mean age 3.2+/-1.8 years) with VBS, who were divided into two groups. The urodynamic study was performed less than 1 year in group 1 (seven boys, aged 1-1.9 years) and more than 1 year in group 2 (nine boys, aged 2.9-6.5 years) after urethral valve fulguration; at the time of operation patients were less than 2 years old. Standards of the International Children's Continence Society were respected, and results were compared between the two groups. Compared to group 1, group 2 showed a significant decrease in maximum detrusor voiding pressure (Pdet.void.max) and bladder compliance (BC), and an increase in post-voiding residual (PVR) and maximum bladder capacity (MBC) (p<0.05), but the difference in detrusor instability was not significant (p>0.05), Pdet.void.max and PVR were 56.2+/-14.1 cmH(2)O and 96.6+/-52.4 ml, respectively, in group 2, and there were more intermittent detrusor contractions during voiding in this group. Patients with VBS frequently present with multiple bladder dysfunctions that can be diagnosed accurately using urodynamics. Even after urethral valve fulguration Pdet.void.max and BC were inclined to decrease, while PVR and MBC increased with the growth of the children.


Optimal algorithms for the interval location problem with range constraints on length and average.
Let A be a sequence of n real numbers, L(1) and L(2) be two integers such that L(1) < or = L(2) , and R(1) and R(2) be two real numbers such that R(1) < or = R(2). An interval of A is feasible if its length is between L(1) and L(2) and its average is between R(1) and R(2). In this paper, we study the following problems: finding all feasible intervals of A, counting all feasible intervals of A, finding a maximum cardinality set of non-overlapping feasible intervals of A, locating a longest feasible interval of A, and locating a shortest feasible interval of A. The problems are motivated from the problem of locating CpG islands in biomolecular sequences. In this paper, we firstly show that all the problems have Omega (n log n)-time lower bound in the comparison model. Then, we use geometric approaches to design optimal algorithms for the problems. All the presented algorithms run in an on-line manner and use O(n) space.


Adapting dried blood spot sampling for an anti-therapeutic antibody immunogenicity assay.
Dried blood spot sampling is a microvolume sampling technique with many potential advantages. It allows for easier handling and less expensive shipment and storage of biological samples. Additionally, it can provide ethical benefits in the pre-clinical setting through a reduction in animal usage by allowing intensive serial sample collection from the same animals. In the clinical setting, ease of sample collection, greater flexibility of sample storage, and shipping are distinct advantages. These advantages can enhance preclinical and clinical data quality, where immunogenicity monitoring plays an important role in the interpretation of pharmacokinetic data. To date, a method for usage of dried blood spot sampling with an immunogenicity assay has not been published. Herein we demonstrate that the measurement of anti-drug antibodies (ADA) using DBS was comparable to traditional methods in terms of reproducibility, assay sensitivity and drug tolerance. The data demonstrate that DBS is a viable sample collection method, and in some cases may be preferred, over classic serum or plasma sampling for antidrug antibody assays.


Alterations in glucose metabolism proteins responsible for the Warburg effect in esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) is the most frequent esophageal tumor in the world. ESCC presents late diagnosis, highly aggressive behavior and poor survival. Changes in tumor cell energy metabolism appear to have a prominent role in malignant transformation. Tumor cells consume glucose avidly and produce lactic acid, even under normoxia. Among the factors that may contribute to the stimulation of glycolysis in tumor cells, there are changes in the glycolytic pathway enzymes such as: pyruvate kinase M1 and M2 (PKM2 and PKM1), hexokinase II (HKII), glucose transporter isoform 1 (GLUT-1), and transcription factor induced by hypoxia (HIF1α), responsible for the transcription of proteins cited. The objective of this study is to evaluate the alterations of these proteins and their association with clinicopathological data in ESCC. We performed immunohistochemistry to determine HIF-1α, GLUT-1, PKM1, PKM2, HK2 and Ki67-expression in ESCC patients and controls. Also, we used RT-qPCR to evaluated mRNA expression of GLUT-1 in esophageal mucosa of individuals without cancer, but are alcohol drinkers and tobacco smokers. Our results showed the exclusively expression of GLUT-1 in tumors cells and dysplastic samples. We also observed a compartmentalization of the expression of PKM1 and PKM2 in relation to tumor cells and stroma associated to tumor areas. All of the proteins evaluated, excepted GLUT-1, were frequently detected in normal mucosa. No correlations between clinicopathological features and protein expressions were observed. GLUT-1 expression appears in initial tumor lesions and is maintained through ESCC evolution. We reported for the first time PKM1 staining in normal esophagus and ESCC, being mostly present in more differentiated cells.


Truncation of subunit ND2 disrupts the threefold symmetry of the antiporter-like subunits in complex I from higher metazoans.
Three of the conserved, membrane-bound subunits in NADH:ubiquinone oxidoreductase (complex I) are related to one another, and to Mrp sodium-proton antiporters. Recent structural analysis of two prokaryotic complexes I revealed that the three subunits each contain fourteen transmembrane helices that overlay in structural alignments: the translocation of three protons may be coordinated by a lateral helix connecting them together (Efremov, R.G., Baradaran, R. and Sazanov, L.A. (2010). The architecture of respiratory complex I. Nature 465, 441-447). Here, we show that in higher metazoans the threefold symmetry is broken by the loss of three helices from subunit ND2; possible implications for the mechanism of proton translocation are discussed.


Quantification ofAspergiullus flavus BFE96 by sybr green Q-PCR in black pepper.
A Real Time PCR system (Q-PCR) for the detection and quantification ofAspergillus flavus in black pepper has been used. Thenor1 gene, a gene of the aflatoxin biosynthetic pathway, served as target sequence. The determined copy numbers of thenor1 gene were compared to the cfu numbers obtained by plate counting. There was not a direct correlation of the results with both approaches, however the tendency was the same. In general both values increased with prolonged incubation time. The differences in copy numbers of thenor1 gene to cfu numbers decreased with increasing incubation time.


Cathepsin L in glioma progression: comparison with cathepsin B.
Lysosomal cysteine cathepsins have been implicated in tumor progression. This study is aimed to reveal differential expression and compare the prognostic significance of cathepsins B and L in glioma patients. The histological slides of 82 patients with primary astrocytic tumors were reviewed. We evaluated the immunostaining of the cathepsins in tumor and endothelial cells. Cathepsins B and L stained positive in 98 and 88% of cases, respectively. The total score was significantly higher in malignant than in benign tumors, both for cathepsin B (p<0.001) and for cathepsin L (p<0.01). The IHC score in endothelial cells in the malignant group was significantly higher only for cathepsin B (p<0.0001). Survival analysis indicated that in contrast to the prognostic significance of total cathepsin B and endothelial cells associated cathepsin B for shorter patients' survival, the prognostic role of cathepsin L was not confirmed. Cathepsin L is preferentially expressed in tumor cells, increasing with glioma progression, but is not significantly associated with new vasculature of glioblastoma. In contrast to cathepsin B, cathepsin L has no prognostic impact, suggesting different roles of the two cathepsins in glioma progression.


The CYP2C8 inhibitor gemfibrozil does not increase the plasma concentrations of zopiclone.
Zopiclone is a short acting hypnotic, which is metabolised by cytochrome P450 (CYP) 3A4 and 2C8 in vitro. We studied the possible effect of gemfibrozil, an inhibitor of CYP2C8, on the pharmacokinetics and pharmacodynamics of zopiclone. In a randomised 2-phase crossover study, 10 healthy volunteers took 600 mg gemfibrozil or placebo orally twice daily for 3 days. On day 3, each ingested a 7.5 mg dose of zopiclone. Plasma concentrations and urinary excretion of zopiclone and its two primary metabolites, plasma gemfibrozil, and psychomotor performance were measured. The effects of CYP2C8, CYP2C9 and CYP3A4 inhibitors on the depletion of zopiclone (500 nM) were studied in vitro in human liver microsomes. The pharmacokinetic variables of the parent zopiclone were not significantly affected by gemfibrozil. However, gemfibrozil raised the mean peak plasma concentration (C(max)) of N-oxide-zopiclone (1.6-fold; P<0.001) and that of N-desmethyl-zopiclone (1.2-fold; P<0.001). The mean area under the plasma concentration-time curve (AUC(0)-infinity) values of N-oxide-zopiclone and N-desmethyl-zopiclone were raised 2-fold (P<0.001) and 1.2-fold (P<0.01), respectively. The renal clearance of N-oxide-zopiclone was reduced by 48% by gemfibrozil (P<0.001). The pharmacodynamic effects of zopiclone, measured using psychometric tests, were not affected by gemfibrozil. In vitro, ketoconazole (1 microM) and itraconazole (8 microM) decreased the elimination rate of zopiclone enantiomers by about 65-95%, while montelukast (16 microM), gemfibrozil (200 microM) and sulfaphenazole (10 microM) had no appreciable effect. Gemfibrozil does not increase the plasma concentrations of the parent zopiclone. Accordingly, CYP2C8 does not significantly metabolise zopiclone in vivo. However, as gemfibrozil raises the concentrations of two potentially active metabolites of zopiclone, slightly enhanced effects of zopiclone by gemfibrozil can not be excluded.


Protein levels of interleukin-12 p70 holomer, its p40 chain and interferon-gamma during advancing HIV infection.
a switch from T helper 1 (TH1) to T helper 2 (TH2)-like cytokine production has been proposed for progressive HIV infection. to study whether this hypothesis is reflected by altered IL-12 and IFN-gamma serum levels in HIV patients. we measured serum levels of IL-12 p40 and p70 and IFN-gamma in 90 HIV seropositive patients at differing disease stages and in 10 healthy controls by radioimmunoassays. These cytokines were compared to established surrogate markers of immunodeficiency. IFN-gamma, as well as IL-12 p40 and p70, levels were significantly increased in HIV patients compared to controls. However, IFN-gamma and IL-12 showed no significant variations with progressive stages of immunodeficiency. IFN-gamma levels showed a significant positive correlation to the progression marker beta2-microglobulin and correlated negatively with CD4+ lymphocyte counts. In addition, IFN-gamma concentrations were related to sTNF-R p55 and p75 serum levels. Interestingly. IFN-gamma was related to IL-12 only with respect to p40, but not to p70. although our data do not necessarily reflect cytokine secretion at the single cell level or the cytokine milieu in the lymphoid microenvironment, our results from peripheral blood fail to demonstrate progressively decreased IL-12 and IFN-gamma serum levels in HIV infected patients.


Inhibition by vitamin C of apoptosis induced by N-nitrosamines in HepG2 and HL-60 cells.
The aim of this study was to evaluate the effect of vitamin C towards N-nitrosopyrrolidine (NPYR)- and N-nitrosodimethylamine (NDMA)-induced apoptosis in human hepatoma (HepG2) and leukemia (HL-60) cell lines using flow cytometry analysis and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay (TUNEL). None of the vitamin C concentrations tested (1-100 microM) caused cytotoxicity in HepG2 cells. However, there were significant losses of HL-60 cells viability, measured by MTT assay, 72 h after treatment with 50 and 100 microM vitamin C (29 and 46%, respectively). Moreover, an increase of lactate dehydrogenase release was significant with 50 microM at 72 h (28%) and with 100 microM of vitamin C at 48 and 72 h (27 and 36%, respectively). Also, the percentage of apoptotic HL-60 cells found in TUNEL assay increased to 21% when they were treated with 100 microM vitamin C for 72 h. Thus, in subsequent simultaneous treatments with NPYR (30 and 50 mM) or NDMA (27 and 68 mM) and vitamin C, concentrations of 5-50 microM vitamin C were used. Our results revealed that vitamin C, at all concentrations and times tested, reduced the apoptosis induced by NPYR and NDMA in both cell lines, showing a similar effect in HepG2 and HL-60 cells towards NPYR (50 mM)--65 and 63% of reduction, respectively--whereas towards NDMA (27 mM) the inhibition was higher in HL-60 than in HepG2 cells--75 and 57%, respectively. Therefore, our findings suggest that inhibition of apoptosis may be one of the mechanisms by which vitamin C exerts its protective effect.


Enrichment of subgingival microflora on human serum leading to accumulation of Bacteroides species, Peptostreptococci and Fusobacteria.
This study was undertaken to identify ecological factors that favour opportunistic pathogenic species in the subgingival microflora. In a first approach, human serum as a substitute for gingival exudate, was used for batch-wise enrichment of subgingival plaque. The microflora resulting after 5-6 enrichment steps consisted of black-pigmented and non-black-pigmented Bacteroides species, Peptostreptococcus micros and Fusobacterium nucleatum as the main organisms. It is noted that the same group of species was found to be enriched independent upon the origin of the subgingival plaque sample. It was suggested that these organisms are favoured by the increased flow of gingival exudate during inflammation. The consortium of organisms was capable of selective degradation of serum (glyco-)proteins. Four different types of degradation occurred. After a prolonged period of growth complete degradation of immunoglobulins, haptoglobin, transferrin and complement C3c was observed. Partial degradation of immunoglobulins, haptoglobin, transferrin, albumin, alpha 1-antitrypsin and complement C3c and C4 was generally observed after 48 h of growth. Besides, immunoglobulin protease activity yielding Fc and Fab fragments was found. The consortium was also capable of consuming carbohydrate side-chains as indicated by an altered electrophoretic mobility of the serum glycoproteins.


An electrophoretic and immunoelectrophoretic characterization of the serum proteins of the adult lamprey, Petromyzon marinus L.
1. Serum proteins of upstream migrants of Petromyzon marinus were separated electrophoretically on polyacrylamide and agarose as well as by crossed immunoelectrophoresis using anti-lamprey serum antiserum. 2. Some constituents of four of the five major bands separated by electrophoresis on polyacrylamide were located in the agarose and crossed-immunoelectrophoretic patterns. 3. Two serum proteins, SDS-1 and CB-III, were isolated. SDS-1 was found to be a glycoprotein; CB-III may be a lipoprotein. 4. Monospecific antisera were produced against SDS-1 and CB-III and were used in crossed immunoelectrophoresis to analyze lamprey serum. This method revealed that electrophoretically different forms of these two proteins exist in serum. 5. Immunoelectrophoretic methods demonstrated that three of the major bands produced by polyacrylamide gel electrophoresis of whole serum contained more than a single protein.


Mycobacterium lepraemurium uses TLR-6 and MR, but not lipid rafts or DC-sign, to gain access into mouse macrophages.
Mycobacterium lepraemurium (MLM), the etiologic agent of murine leprosy, is an intracellular parasite of macrophages; the mechanism used by this bacterium to enter macrophages is not known. The fate of the MLM phagosome inside macrophages is also unknown. This study was conducted to investigate how MLM enters macrophages and to define the maturation process of MLM phagosome inside macrophages. Peritoneal macrophages were incubated in the presence of mannan-bovine serum albumin (BSA), and antibodies to known macrophage receptors, including, anti-FcγRIII/RII (anti-CD16/32), anti-CD35 (anti-CR1), anti-TLR2, anti-TLR4, anti-TLR6, anti-CD14, and anti-dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN). Then, macrophages were challenged with Iris Fuchsia-stained MLM, at a multiplicity of infection of 50:1. The blocking effect of the antibodies (and mannan-BSA) used was analyzed using direct microscopy and flow cytometry. The maturation process of MLM phagosomes was visualized by their interaction with antibodies to Rab5, Rab7, proton ATPase, and cathepsin D, by confocal microscopy. Only mannan-BSA and anti-TLR6 antibody significantly blocked the entry of MLM into macrophages. None of the other antibodies, including that for DC-SIGN, meaningfully inhibited the endocytic process. We also found that MLM is a fusiogenic mycobacterium. This was deduced from the orderly association of MLM phagosomes with Rab5, Rab7, Proton ATPase, and lysosomes (cathepsin D). Fusion of MLM phagosomes with lysosomes seems to be a necessary event for the intracellular multiplication of MLM; similar to Mycobacterium leprae, this microorganism hardly grows on artificial, synthetic, bacteriologic media.


Meta-analysis of local gentamicin for prophylaxis of surgical site infections in colorectal surgery.
Surgical site infections (SSIs) following colorectal surgery is common, and local application of gentamicin for SSIs in the surgery remains controversial. To identify whether local application of gentamicin reduces incidence of SSIs in colorectal surgery. PubMed, Embase, the Cochrane Library, and Science Citation Index were searched for relevant randomized controlled trials (RCTs) and reference list up to November 2014. Two independent reviewers screened the records from the electronic databases, selected relevant studies, assessed the methodological quality, and extracted the data from included articles. Stata 12.0 was used to conduct a pooled analysis for main outcomes. Eight relevant randomized controlled trials with a total of 1685 patients were included in the meta-analysis. All included studies were of moderate to high quality by the Cochrane Collaboration's tool for assessing risk of bias. There was no significant difference being found in the total pooled results for wound infection (relative risk (RR) 0.73, 95% confidence interval (CI) 0.47 to 1.12) and organ space infection (RR 0.90, 95% CI 0.51 to 1.59). However, subgroup analysis showed that the significant decrease of wound infection was associated with the population in the Western Europe (RR 0.60, 95% CI 0.42 to 0.87) and follow-up periods of 30 days (RR 0.63, 95% CI 0.42 to 0.94). Local application of gentamicin significantly reduced incidence of wound infection following colorectal surgery in Western Europe, and it was also associated with lower risk of wound infection during follow-up period of 30 days. However, its effectiveness on prophylaxis of perineal wound infection and organ space infection still lacked evidence.


Hypoxanthine transport through the blood-brain barrier.
The unidirectional influx of hypoxanthine across cerebral capillaries, the anatomical locus of the blood-brain barrier, was measured with an in situ rat brain perfusion technique employing [3H]hypoxanthine. Hypoxanthine was transported across the blood-brain barrier by a saturable system with a one-half saturation concentration of approximately 0.4 mM. The permeability-surface area product was 3 X 10(-4) sec-1 with a hypoxanthine concentration of 0.02 microM in the perfusate. Adenine (4 mM) and uracil and theophylline (both 10 mM), but not inosine (10 mM) or leucine (1 mM), inhibited hypoxanthine transfer through the blood-brain barrier. Thus, hypoxanthine is transported through the blood-brain barrier by a high-capacity, saturable transport system with a half-saturation concentration about 100 times the plasma hypoxanthine concentration. Although involved in the transport hypoxanthine from blood into brain, this system is not powerful enough to transfer important quantities of hypoxanthine from blood into brain.


Factors predicting reclassification of variants of unknown significance.
Genetic variants of unknown significance (VUS) are an increasingly common result of genetic testing. VUS present dilemmas for treatment and surveillance. Family history may play a role in VUS reclassification over time. All genetic tests performed at a tertiary referral center 2006-2015 were evaluated for the presence of VUS. Patients with VUS were evaluated for demographics, clinical characteristics, family history, and gene characteristics. In total, 2291 individuals were tested from 1639 families; 150 VUS were identified. Twenty-eight VUS reclassified, 21 to benign and 7 to pathogenic. Logistic regression demonstrated the number of family members with associated phenotypic disease was a significant predictor of reclassification. The likelihood of VUS reclassification can be predicted by increased positive family history of disease. Most VUS reclassify to benign, but one-fourth reclassify to pathogenic. The actual risk of a VUS should be assessed based on family history and routinely checked for reclassification.


Incidence of Arthritis/Arthralgia in Inflammatory Bowel Disease with Long-term Vedolizumab Treatment: Post Hoc Analyses of the GEMINI Trials.
Extraintestinal manifestations [EIMs] such as arthritis/arthralgia are common in inflammatory bowel disease. We performed post hoc analyses of data from the GEMINI studies to evaluate the effect of vedolizumab, a gut-selective anti-trafficking agent, on arthritis/arthralgia. Sustained resolution of baseline arthritis/arthralgia, worsening of baseline arthritis/arthralgia, the occurrence of new arthritis/arthralgia, and the composite of new/worsening arthritis/arthralgia were evaluated. Cox modelling was used for time-to-event analysis. The influence of corticosteroid-tapering was also investigated. In Crohn's disease [CD] patients, vedolizumab was significantly less likely than placebo to be associated with new/worsening arthritis/arthralgia (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.44-0.89). Similar incidences of sustained resolution of arthritis/arthralgia occurred with vedolizumab and placebo. In CD patients on corticosteroids at baseline, a decrease in corticosteroid dose increased the risk of new/worsening arthritis/arthralgia (odds ratio [OR], 7.49; 95% CI, 3.50-15.97) regardless of treatment; and in those achieving corticosteroid-free status, arthritis/arthralgia was less likely with vedolizumab than with placebo [HR, 0.14; 95% CI, 0.05-0.35]. In ulcerative colitis [UC] patients, vedolizumab and placebo showed a similar incidence of new/worsening of arthritis/arthralgia. In UC patients on corticosteroid at baseline, arthritis/arthralgia was more likely in those achieving corticosteroid-free status than in those continuing corticosteroids (HR 2.63 [95% CI 1.13-6.11]); and in those achieving corticosteroid-free status, the incidence of arthritis/arthralgia was similar with vedolizumab and placebo. Vedolizumab therapy was associated with a reduced likelihood of new/worsening arthritis/arthralgia in CD and no increased incidence of these events in UC. GEMINI 1 [NCT00783718]; GEMINI 2 [NCT00783692]; GEMINI 3 [NCT01224171].


Elevation of granulocyte-macrophage colony-stimulating factor in the placenta and blood in preeclampsia.
This study investigated whether granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in the placenta and blood in preeclampsia differed from those in normal pregnancies. Macrophage colony-stimulating factor (M-CSF) levels in the placenta were also measured. The subjects were 44 pregnant women carrying single fetuses, of whom 22 were women with normal pregnancies and 22 were women with preeclampsia. Their average gestational age at entry was 37 to 38 weeks of gestation. Peripheral blood was collected before the onset of labor. Separated serum was obtained after centrifugation and stored at -20 degrees C. A tissue segment of the placenta was cut immediately after delivery. The frozen placental tissue was placed into a plastic tube containing phosphate-buffered saline solution. The tissue was fully homogenized and then centrifuged. Separated supernatant was frozen at -80 degrees C for subsequent determination. GM-CSF levels in separated serum were measured, and GM-CSF, M-CSF, and total protein (TP) levels in separated supernatant were also measured. Not only GM-CSF levels in blood but also GM-CSF/TP levels in the placenta were significantly higher (P<.05) in preeclampsia than in normal pregnancies. Similar results were obtained for M-CSF/TP levels in the placenta. We demonstrated a significant increase in placenta levels of GM-CSF/TP in preeclampsia. Elevated GM-CSF in the placenta may be related to immunologic abnormalities contributing to the etiology of preeclampsia.


Purification of gamma-enolase messenger ribonucleic acid from rat brain by an immunoadsorption method.
Messenger ribonucleic acid (mRNA) coding for the brain-specific protein gamma-enolase was isolated by an immunopurification procedure. Rat brain polysomes including nascent polypeptide chains were reacted with specific gamma-enolase antibody. The polysome-antibody complexes were subsequently adsorbed to protein A-Sepharose. After extensive washing, RNA was eluted and applied to an oligo(dT)-cellulose column. Purified mRNA was translated in vitro in a mRNA-dependent rabbit reticulocyte lysate system. The synthesized product was identical to gamma-enolase synthesized by free polysomes from rat brain. Immunoisolated gamma-enolase mRNA was enriched 380-fold compared to total mRNA extracted from free polysomes. This result indicates that low-abundance mRNAs may conveniently be isolated from brain tissue by immunoadsorption of polysomes.


Disopyramide and N-monodesalkyl disopyramide in serum and breast milk.
Maternal serum and breast milk were obtained to determine the concentration of disopyramide (DP) and its metabolite N-monodesalkyl disopyramide (NMD) from a woman requiring antidysrhythmic drug therapy. Infant serum and urine were also obtained for drug concentrations. DP 450 mg tid resulted in peak maternal serum concentrations of 4.0 micrograms/mL and 2.2 micrograms/mL for DP and NMD, respectively. Breast milk concentrations averaged 1.06 and 6.24 times the serum levels for DP and NMD, respectively. No DP was measurable in the infant's serum except for cord blood, which contained 0.7 micrograms/mL DP, 26 percent of simultaneous maternal concentration, and 0.9 micrograms/mL NMD, which represented 43 percent of the maternal concentration. Infant urine collected over an eight-hour period contained 3.3 micrograms/mL of DP and 3.7 micrograms/mL of NMD.


Radiologic investigations and pathologic results of experimental chronic pancreatitis in cats.
The purpose of this study was to evaluate a variety of methods to induce chronic pancreatitis and its radiologic expression by experimentally inducing this condition in cats. Chronic inflammatory and fibrosing pancreatitis was produced in cats by intraductal injection of 1.5 mL of 94% ethanol in one group or by a combination of intraductal and intraparenchymal injection of ethanol together with partial obstruction of the main pancreatic duct to 70% of its original lumen by fixation of a small catheter in the papilla. For comparison, other cats underwent total obstruction of the main pancreatic duct. All groups, as well as untreated control cats (n = 3), underwent repeat laparotomy to obtain biopsy specimens. Cats with total obstruction showed progressing fibrosis with dilatation of ductules occasionally infiltrated with granulocytes. From 26 weeks on, acini and islets of Lnagerhans became atrophic. Radiographs showed progressive but diffuse dilatation of ducts, ductules, and side branches. Cats from the other two groups had interlobular inflammation and fibrosis with flattened and irregular ductular epithelium. Later, ductular proliferation occurred, interstitial inflammation subsided, and fibrosis increased. Radiographs showed very irregular ducts and ductules with stenosis and dilatation. From 26 weeks on, no substantial differences were observed between the cats who received only intraductal injection of ethanol and the cats who underwent the combination of procedures. The histopathologic and radiographic alterations that evolved from damage to the ductal epithelium in the cat resembled the features of chronic pancreatitis in humans and differed from those caused by total obstruction of the main pancreatic duct in cats.


Brachial plexus neuropathy following mantle radiotherapy.
We report two cases of presumed radiation-induced brachial plexus neuropathy in patients with lymphoma who were treated with standard mantle radiotherapy to a dose of 40 Gy in 20 fractions. Radiation-induced brachial plexopathy has not previously been reported following mantle irradiation at this dose. Both patients received chemotherapy in relapse. We postulate three possible causes: enhanced radiation sensitivity; an interaction between the chemotherapy and the radiotherapy; or an increased dose in axilla owing to a smaller separation at that point.


Heterogeneity of rat plasma albumin and drug binding.
Rat plasma albumin fractionated by Sephadex G-75 (superfine) gel filtration from freshly prepared rat plasma was further separated into three major fractions by chromatofocusing column chromatography. All the fractionated albumins had high binding affinity for the fluorescent probe 8-anilino-1-naphthalenesulfonic acid, as the model compound for acidic drugs, and were found to be immunologically identical.


Current knowledge on the mechanism of atherosclerosis and pro-atherosclerotic properties of oxysterols.
Due to the fact that one of the main causes of worldwide deaths are directly related to atherosclerosis, scientists are constantly looking for atherosclerotic factors, in an attempt to reduce prevalence of this disease. The most important known pro-atherosclerotic factors include: elevated levels of LDL, low HDL levels, obesity and overweight, diabetes, family history of coronary heart disease and cigarette smoking. Since finding oxidized forms of cholesterol - oxysterols - in lesion in the arteries, it has also been presumed they possess pro-atherosclerotic properties. The formation of oxysterols in the atherosclerosis lesions, as a result of LDL oxidation due to the inflammatory response of cells to mechanical stress, is confirmed. However, it is still unknown, what exactly oxysterols cause in connection with atherosclerosis, after gaining entry to the human body e.g., with food containing high amounts of cholesterol, after being heated. The in vivo studies should provide data to finally prove or disprove the thesis regarding the pro-atherosclerotic prosperities of oxysterols, yet despite dozens of available in vivo research some studies confirm such properties, other disprove them. In this article we present the current knowledge about the mechanism of formation of atherosclerotic lesions and we summarize available data on in vivo studies, which investigated whether oxysterols have properties to cause the formation and accelerate the progress of the disease. Additionally we will try to discuss why such different results were obtained in all in vivo studies.


Arterial spin labeling MRI applied to migraine: current insights and future perspectives.
Advanced neuroimaging techniques have extensively contributed to elucidate the complex mechanisms underpinning the pathophysiology of migraine, a neurovascular disorder characterized by episodes of headache associated with a constellation of non-pain symptoms. The present manuscript, summarizing the most recent progresses of the arterial spin labelling (ASL) MRI techniques and the most significant findings from ASL studies conducted in migraine, is aimed to clarify how ASL investigations are contributing to the evolving insight on migraine pathophysiology and their putative role in migraine clinical setting. ASL techniques, allowing to quantitatively demonstrate changes in cerebral blood flow (CBF) both during the attacks and in the course of interictal period, could represent the melting point between advanced neuroimaging investigations, conducted with pure scientific purposes, and conventional neuroimaging approaches, employed in the diagnostic decision-making processes. Converging ASL evidences have demonstrated that abnormal CBF, exceeding the boundaries of a single vascular territory, with biphasic trend dominated by an initial hypoperfusion (during the aura phenomenon but also in the first part of the headache phase) followed by hyperperfusion, characterizes migraine with aura attack and can represent a valuable clinical tool in the differential diagnosis from acute ischemic strokes and epileptic seizures. Studies conducted during migraine without aura attacks are converging to highlight the involvement of dorsolateral pons and hypothalamus in migraine pathophysiology, albeit not able to disentangle their role as "migraine generators" from mere attack epiphenomenon. Furthermore, ASL findings tend to support the presence of perfusion abnormalities in brain regions known to be involved in aura ignition and propagation as well as in areas involved in multisensory processing, in both patients with migraine with aura and migraine without aura. Although ASL studies have dramatically clarified quality and timing of perfusion abnormalities during migraine with aura attacks, the same cannot be said for perfusion changes during migraine attacks without aura and interictal periods. Future studies with more rigorous methodological approaches in terms of study protocol, ASL technique and sample selection and size are mandatory to exploit the possibility of better understanding migraine pathophysiology and identifying neuroimaging biomarkers of each migraine phase in different migraine phenotypes.


Improving rigor through gender inclusivity in reproductive psychiatric science.
Accurately defining the individuals that research involves and generalizes to is critical for rigorous and reproducible science. In reproductive psychiatry, which historically focuses on the impact of the menstrual cycle, pregnancy, and menopause on mental health, this means moving beyond characterizing samples and relevant populations as "women" in favor of language that precisely identifies the physiological characteristics pertinent to the research being conducted and accurately reflects the varied genders represented in those populations. Concrete recommendations are provided for precise use of sex and gender terminology and gender inclusivity throughout the scientific process, including study conceptualization, etiquette in research environments, recruitment, methods, and dissemination. Recommendations are discussed in depth and presented in a checklist format for ease of use by research teams. Suggested items for assessing gender and relevant sex-related physiology in the context of reproductive psychiatry are also provided.


Ab initio fragment molecular orbital study of ligand binding to human progesterone receptor ligand-binding domain.
We applied the fragment molecular orbital (FMO) method, which enables total electronic calculations of large molecules at ab initio level, to the evaluation of binding affinities between the human progesterone receptor ligand-binding domain (PR LBD) and various steroidal ligands. The FMO calculations were performed on the entire structure of the PR LBD, which is composed of approximately 4,100 atoms. Our computational binding energies of PR LBD/ligand complexes agreed well with experimental binding affinities (r=0.909). Interaction energies between each ligand and specific amino acid residues were also obtained from the FMO calculations. The principal residues involved in the interactions with these ligands were Arg766 and Asn719, with some additional contribution by Gln725. The main factor determining differences in binding affinity of the various ligands was not interactions with particular residues, but with the binding-site residues closest to the ligand. The interfragment interaction energy analysis is proving to be a useful method for gaining detailed information on ligand binding.


Photosensitized formation of ascorbate radicals by chloroaluminum phthalocyanine tetrasulfonate: an electron spin resonance study.
The chloroaluminum phthalocyanine tetrasulfonate sensitized photooxidation of ascorbic acid to ascorbate radical (A.-) was followed by electron spin resonance (ESR) spectroscopy. In air saturated aqueous media, steady-state amounts of A.- are rapidly established upon irradiation. The ESR signal disappears within a few seconds after the light is extinguished--more slowly under constant irradiation as oxygen is depleted. No photooxidation was observed in deaerated media. The effect of added superoxide dismutase, catalase, desferrioxamine, and singlet oxygen scavengers (NaN3 and tryptophan) was studied, as was replacement of water by D2O and saturation with O2. The results are indicative of free radical production by direct reaction between ascorbate ion and sensitized phthalocyanine (a Type I mechanism) in competition with the (Type II) reaction of HA- with singlet oxygen, a reaction which does not produce ascorbate radical intermediates.


Intravitreal triamcinolone acetonide for pseudophakic cystoid macular edema.
To report the clinical outcome of patients undergoing intravitreal injection of triamcinolone acetonide as treatment of long-standing cystoid macular edema after phacoemulsification. Prospective clinical interventional cases series studies. The study included five patients suffering from cystoid macular edema after cataract surgery. They received an intravitreal injection of 25-mg crystalline triamcinolone acetonide transconjunctivally with topical anesthesia. In the follow-up period of 6.6 +/- 4.1 months, visual acuity increased from 0.26 +/- 0.13 to a mean maximal visual acuity of 0.60 +/- 0.19. For all patients, visual acuity improved during the follow-up by at least 0.20. Two (40%) patients developed intraocular pressure values higher than 21 mm Hg, which could be controlled by topical antiglaucomatous treatment. Intravitreal triamcinolone acetonide may be a therapeutic option for long-standing cystoid macular edema after cataract surgery.


Leishmania (Viannia) braziliensis is the prevalent species infecting patients with tegumentary leishmaniasis from Mato Grosso State, Brazil.
The frequency of Leishmania (Viannia) braziliensis infection among patients of Mato Grosso, Brazil was estimated by polymerase chain reaction-PCR, DNA hybridization and by isoenzyme electrophoresis. Analysis of DNA polymorphism was carried out using random amplified polymorphic DNA-PCR (RAPDPCR) with five different primers. The patients were attended from May 1997 to February 1998 at the Reference Ambulatory for American Tegumentary Leishmaniasis at Júlio Müller University Hospital of the Federal University of Mato Grosso, Brazil. In a first screening by PCR and DNA hybridization 94.1% of 68 patients, from whom parasites were isolated in culture medium, were found to be infected with species of the Le. braziliensis complex. Only four patients (5.9%) were infected with species of Le. mexicana complex. Thirty-three samples of Le. braziliensis complex and three of Le. mexicana complex were typed by isoenzyme analysis as Le. (V.) braziliensis sensu stricto and Le. (Leishmania) amazonensis, respectively. The predominant species was Le. (V.) braziliensis, although most of the patients of this study came from the northern area of Mato Grosso, which is part of the Amazonian region of Brazil, where other known species of both subgenus Viannia (Le. braziliensis complex) and Leishmania (Le. mexicana complex) are present. The results of RAPD showed higher genetic variability among the Le. (V.) braziliensis samples from Mato Grosso. The importance of these results concerning the taxonomic status of New World Leishmania, and their implications for both clinical and epidemiological data is discussed.


Emerging concepts in nutrigenomics: a preview of what is to come.
This article provides an overview of the fundamental principles of genetics and emerging concepts related to the ways in which nutrients and bioactive food components may interact with the genome and subsequently affect human health. This exciting area of research is likely to have far-reaching implications for the assessment and treatment of critically and chronically ill individuals that will affect nutrition standards of care and practice. A brief overview of some of the ethical, legal, and social implications of genomic research and genome-based health care and a list of genetics resources also are provided.


Screening of African sera stored for more than 17 years for HIV antibodies by site-directed serology.
Antibodies to Human Immunodeficiency Virus type 1 (HIV-1) and type 2 (HIV-2) were investigated, using site-directed enzyme immunoassay (ELISA), in 320 specimens obtained from three remote, African tribes during 1969-1971. Using HIV-1 E34/E32 ELISA and HIV-2 149 ELISA, assay were conducted on 101 serum specimens from the Korekore tribe of Zimbabwe, 93 specimens from the Mano tribe of Liberia, and 126 specimens from the Turkana tribe of Kenya; specimens which tested positive in ELISA were further tested by radioimmunoprecipitation assay (RIPA) and Western blot (WB). Two serum specimens from the Mano tribe of Liberia gave OD 492 nm values greater than 0.2 in HIV E34/E32 ELISA in all three runs. These two specimens reacted with HIV-1 envelope proteins gp160 and gp120 and the internal protein p24 in RIPA and WB; however, the reactivity was uncostant. All other serum specimens were negative for HIV-1 and HIV-2 antibodies. Site directed ELISA serology for HIV-1 and HIV-2 gave very low rates of false positive reactivity. Thus, reaction with HIV-1 antigen was identified in two persons of one tribe in Liberia in 1971, but HIV-2 antibodies were not detected in this tribe; HIV-1 and HIV-2 antibodies were absent during the late 1960's and early 1970's from two African tribes resident in Zimbabwe and Kenya.


Optimal detection of extended-spectrum β-lactamase producers, carbapenemase producers, polymyxin-resistant Enterobacterales, and vancomycin-resistant enterococci from stools.
This study compared the impact of different approaches, namely, nonenrichment, nonselective enrichment, and selective (antibiotic-containing) enrichment steps, for detecting extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), carbapenemase-producing Enterobacterales (CPE), polymyxin-resistant Enterobacterales (PMR-E), and vancomycin-resistant enterococci (VRE) from spiked stools. The use of a nonselective 18-h enrichment broth culture significantly improved the recovery rate of all types of resistant bacteria after their plating onto selective media. In addition, the detection of ESBL-E, CPE, PMR-E, and VRE was further improved when using an enrichment step using antibiotic-supplemented broths respectively supplemented with cefotaxime (0.1 μg/mL), ertapenem (0.1 μg/mL), colistin (0.5 μg/mL), and vancomycin (1 μg/mL). Therefore, we showed here that a screening strategy based on a selective broth enrichment step significantly contributes to an increased rate of detection of multidrug-resistant bacteria, which may be crucial in term of improvement of infection control.


Final results from phase II trial of neoadjuvant docetaxel and capecitabine given sequentially or concurrently for HER2-negative breast cancers.
The combination of docetaxel and capecitabine has been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in patients with metastatic breast cancer compared with docetaxel alone. We hypothesized that the combination of docetaxel and capecitabine, given concomitantly or sequentially, would present a nonanthracycline-based treatment option for patients with early stage and locally advanced breast cancer. Patients with stage I to stage IIIC, human epidermal growth factor receptor 2-negative (HER2(-)) breast cancer were randomly assigned to receive either docetaxel followed by capecitabine (D → C) or docetaxel administered concomitantly with capecitabine (DC). Between April 2007 and July 2009, 51 patients were accrued to the trial at an academic center, a county hospital, and community sites. Median tumor size was 3.8 cm and > 70% of patients had axillary lymph node involvement. Fifty-seven percent of patients accrued were African American. Twenty-one of the 51 subjects had triple-negative breast cancer. The pathologic complete response (pCR) rate was 8% in the D → C arm; 12% in the DC arm. The pCR rate among patients with triple-negative breast cancer was 19%. The combination of docetaxel and capecitabine has modest activity in the neoadjuvant setting. These results are consistent with other trials using this combination in the neoadjuvant setting.


Effects of topically administered FK506 on sciatic nerve regeneration and reinnervation after vein graft repair of short nerve gaps.
Despite the development of various nerve coaptation materials and techniques, achievement of desired functional peripheral nerve regeneration is still inadequate, and repair of peripheral nerve injuries is still one of the most challenging tasks and concerns in neurosurgery. The effect of an FK506-loaded vein graft as an in situ delivery system for FK506 in bridging the defects was studied using a rat sciatic nerve regeneration model. A 10-mm sciatic nerve defect was bridged using an inside-out vein graft (IOVG) filled with 10 μl of a carrier-drug dilution (10 ng/ml FK506) in the IOVG/FK506 group. In the IOVG control group, the vein was filled with the same volume of carrier dilution alone. The regenerated fibers were studied 4, 8, and 12 weeks after surgery. Functional study confirmed faster recovery of the regenerated axons in the IOVG/FK506 group than in the IOVG group (p < 0.05). There was a statistically significant difference between the mean gastrocnemius muscle weight ratios of the IOVG/FK506 and IOVG control groups (p < 0.05). Morphometric indices of regenerated fibers showed that the number and diameter of the myelinated fibers were significantly higher in the IOVG/FK506 group than in the IOVG control group. Immunohistochemical analysis showed more positive immunoreactivity to S100 protein in the IOVG/FK506 group than in the IOVG control group. When loaded in a vein graft, FK506 resulted in improvement of functional recovery and quantitative morphometric indices of sciatic nerve. Topical application of this readily available agent offers the benefit of cost savings as well as avoiding the complications associated with systemic administration.


Laparoscopic segment VI liver resection using a left lateral decubitus position: a personal modified technique.
Laparoscopic technique for lesions located in the left liver is well described in the literature. On the contrary, the best laparoscopic approach for lesions located in the right liver, such as in segment VI, is still debated. In this article, we provide a detailed description of a laparoscopic segment VI liver resection using a left lateral decubitus position with the right side up, facilitated by a personal technique. We also discuss potential advantages and disadvantages of this procedure.


Medical school selection criteria and the prediction of academic performance.
To assess how well prior academic performance, admission tests, and interviews predict academic performance in a graduate medical school. Analysis of academic performance of 706 students in three consecutive cohorts of the 4-year graduate-entry medical program at the University of Queensland. Proportion of academic performance during the medical program explained by selection criteria, and correlation between selection criteria and performance. Selection criteria were grade point average (GPA), GAMSAT (Graduate Australian Medical School Admissions Test) score, and interview score. Academic performance was defined as overall total in all examinations combined, in first and fourth year examinations, and in individual written, ethics and clinical components. Selection criteria explained 21.9% of variation in overall total score, falling from 28.2% in Year 1 to 17.7% in Year 4. This was highest for the written examination in Year 1 (30.5%) and lowest for the clinical examination in Year 4 (10.9%). GPA was most strongly correlated with academic performance (eg, for overall score, partial Spearman's correlation coefficient [pSCC], 0.47; P < 0.001), followed by interviews (pSCC, 0.12; P = 0.004) and GAMSAT (pSCC, 0.07; P = 0.08). The association between GPA and performance waned from Year 1 to Year 4, while the association between interview score and performance increased from Year 1 to Year 4. The school's selection criteria only modestly predict academic performance. GPA is most strongly associated with performance, followed by interview score and GAMSAT score. The school has changed its selection process as a result.


The 577-nm pro-yellow diode laser as a reliable and effective tool for facial telangiectasia.
Laser treatment of vascular skin conditions is very useful option yet remains to be a very challenging task. To evaluate the efficacy of 577-nm diode laser for treating facial telangiectasia. Thirty patients with facial telangiectasia were included in this prospective study. All participants received 3 sessions of a single-pass 577-nm diode laser. Sessions were delivered on a monthly basis, and digital photographic assessment was made at baseline and on follow-up 1 month after the last treatment. At the final visit, there was a significant improvement (> 50%) reported in 21/30 (70%) patients while a poor response was reported in 2/30 (6.7%) patients. The skin phototype and site of the lesions significantly affected the result outcome (P < .05) while none of the patients' age, sex, or duration of facial telangiectasia significantly affected the treatment outcome (P > .05). Postinflammatory hyperpigmentation occurred in 2(6.7%) patients which resolved within 1.5 months. Facial telangiectasia can be successfully treated with a 577-nm diode laser with minimal side effects.


Quantitative analysis of dual-phase enhanced CT in cervical lymph node metastasis of papillary thyroid carcinoma: a comparative study along with pathological manifestations.
This study aimed to investigate the diagnostic value of dual-phase enhanced computed tomography (CT) in the cervical lymph node metastasis (LNM) of papillary thyroid carcinoma (PTC) by analyzing the dual-phase enhanced Hounsfield units (HUs) of lymph node and sternocleidomastoid muscle, and the ratio and difference. The CT arterial-phase and venous-phase imaging data of 143 metastasis-positive lymph nodes (MPLNs) in 88 cases and 172 metastasis-negative lymph nodes (MNLNs) in 128 cases with PTC were retrospectively analyzed. All lymph nodes were confirmed by surgical pathology. The arterial-phase HU of lymph nodes (ANHU), venous-phase HU of lymph nodes (VNHU), arterial-phase HU of the sternocleidomastoid muscle (AMHU) and venous-phase HU of the sternocleidomastoid muscle (VMHU) were measured, and their difference and ratio (ANHU-AMHU, ANHU/AMHU, VNHU-VMHU, VNHU/VMHU) were calculated. The cutoff values and corresponding diagnostic efficacy for diagnosing LNM in PTC were sought by performing the receiver operating characteristic curves. The maximum pathological diameter (MPD) measured on pathological sections of lymph nodes was compared with the maximum transverse diameter (MTD) and maximum sagittal diameter (MSD) and their average values on CT images. The ANHU, and VNHU of MPLNs and MNLNs were 111.89 ± 33.26 and 66.12 (56.81-76.86) (P < 0.001), and 99.07 ± 23.27 and 75.47 ± 13.95 (P < 0.001), respectively. The area under the curve, sensitivity, and specificity of the arterial-phase three parameters (ANHU, ANHU-AMHU, ANHU/AMHU) for diagnosing LNM were (0.877-0.880), (0.755-0.769), and (0.901-0.913), respectively, and the venous-phase three parameters (VNHU, VNHU-VMHU, VNHU/VMHU) were (0.801-0.817), (0.650-0.678), and (0.826-0.901), respectively. Compared with MPD, MTD (Z = -2.686, P = 0.007) and MSD (Z = -3.539, P < 0.001) were significantly different, while (MTD + MSD)/2 was not statistically different (Z = -0.038b, P = 0.969). In the differential diagnosis of cervical LNM of PTC by dual-phase enhanced CT angiography, the arterial phase had higher diagnostic efficacy.


Bis(7)-tacrine prevents glutamate-induced excitotoxicity more potently than memantine by selectively inhibiting NMDA receptors.
We have recently reported that bis(7)-tacrine could prevent glutamate-induced neuronal apoptosis through NMDA receptors. In this study, we demonstrated that in cultured rat cortical neurons, bis(7)-tacrine (IC(50), 0.02 microM) prevented glutamate-induced excitotoxicity more substantially than memantine (IC(50), 0.7 microM). In addition, bis(7)-tacrine was more efficient than memantine in buffering the intracellular Ca(2+) triggered by glutamate. In cultured rat hippocampal neurons, bis(7)-tacrine inhibited 50 microM NMDA-activated current in a concentration-dependent manner with an IC(50) of 0.68+/-0.07 microM, which is five times more potent than that produced by memantine (IC(50), 3.41+/-0.36 microM; p<0.05). By contrast, bis(7)-tacrine, up to 5 microM, did not significantly affect the current activated by 50 microM AMPA or 50 microM kainate. These results suggest that bis(7)-tacrine is more potent than memantine against glutamate-induced neurotoxicity by selectively inhibiting NMDA-activated current.


Large Cell Neuroendocrine Carcinoma Shares Similarity with Small Cell Carcinoma on the Basis of Clinical and Pathological Features.
Large cell neuroendocrine carcinoma (LCNEC) was categorized into pulmonary neuroendocrine tumors (NETs) according to the World Health Organization classification guideline. However, LCNEC patients often received the chemotherapy regimens similar to non-small cell lung carcinoma (NSCLC) in advanced stage and the therapeutic effect was unsatisfactory. Therefore, this study aimed to investigate the hidden clinical features, prognosis and immunoprofile of the LCNEC, compared with carcinoid and SCLC, to explore whether LCNEC shares similarity with SCLC and potential treatment approaches could be revealed. One hundred seventeen pulmonary NETs cases were retrospectively retrieved in this study. The Kaplan-Meier estimator was employed to draw survival curves. Immunohistochemistry was applied to detect NET-related markers expression. In clinical features, compared with carcinoid, LCNEC patients were older, more commonly in male and advanced stage. The parallel phenomena were also found in the high-grade subgroup when compared with the low- to intermediate-grade one. In survival analysis, the 5-year overall survival of LCNECs was 59.1%, which was poorer than that of carcinoids, but better than that of SCLCs. Immunohistochemistry showed that p53 and PTEN functional inactivation, up-regulation of CD117 expression, down-regulation of SSR2A and SSR5 expression were commonly involved in LCNECs when compared with carcinoids, or in the high-grade subgroup when compared with the low- to intermediate-grade one. However, no significant difference was found in the comparison between LCNECs and SCLCs, or NSCLCs and SCLCs. In clinical features, survival and immunoprofile, LCNEC showed more similarity with SCLC rather than carcinoid, which might guide novel therapy for pulmonary NETs.


Age-related changes in brain functional networks under multisensory-guided hand movements assessed by the functional near - Infrared spectroscopy.
This study aims to explore the age-related effects of hand rehabilitation training under multisensory stimulation interaction on brain functional networks. A multisensory stimulation training glove (MSTG) was designed to realize 3 sensory guidance modes, namely audio-visual guidance (AVG), visual guidance (VG) and no guidance (NG). This study recruited 20 older subjects as the experimental group and 22 young people as the control group. Functional near-infrared spectroscopy (fNIRS) was used to monitor haemoglobin concentration in the motor cortex (MC), prefrontal cortex (PFC), temporary lo be (TL) and occipital lobe (OL) under three different guidance stages, and further analysed the cortical activation and functional connectivity (FC). Multisensory guidance stage showed more activation and higher FC in all subjects. The activated brain regions of the older subjects showed bilateral activation, which is consistent with the Hemispheric Asymmetry Reduction in Older Adults (HAROLD) model. In terms of brain region coordination, older people have a more balanced and denser functional network in the left and right hemispheres compared to younger people. Meanwhile, multisensory stimulation produced a positive training effect on the number of training and reaction time. Audio-visual combined stimulation had a significant gain effect on hand training at different ages. However, older adults induce a wider range of cortical activations. At the same time, young and older people have different intercortical coordination networks. All these results provide theoretically and applied references for multisensory stimulation in the prevention and rehabilitation of ageing and brain neurological disorders.


Screening of halogenated aromatic compounds in some raw material lots for an aluminium recycling plant.
Four samples of scrap raw materials for an aluminium recycling plant were screened for the occurrence of persistent halogenated aromatic compounds. The samples contained waste from handling of electric and electronic plastics, filter dust from electronic crusher, cyclone dust from electronic crusher and light fluff from car shredder. In our screening analyses, brominated flame retardants were observed in all samples. Polybrominated diphenyl ethers (PBDE) were identified in all samples in amounts of 245-67450 ng/g. The major PBDE congeners found were decabromo- and pentabromodiphenyl ethers. 1,1-bis(2,4,6-tribromophenoxy)ethane, hexabromobenzene, ethyl-pentabromobenzene, tetrabromobisphenol-A, pentabromotoluene and dimethyl tetrabromobenzene were observed in all scrap samples. The concentrations of PCBs, PCNs (polychlorinated naphthalenes) and nona- to undecachlorinated terphenyls in some of these scrap samples were remarkably high.


Viridans streptococcal bacteremia after esophageal stricture dilation.
The incidence of bacteremia with organisms that may cause infective endocarditis after esophageal stricture dilation is unknown. There is disagreement among physicians regarding the need for antibiotic prophylaxis for patients with valvular heart disease undergoing dilation. Our aim was to determine the frequency and duration of bacteremia associated with esophageal stricture dilation. Blood cultures were obtained before and after stricture dilation in patients without valvular heart disease and in a control group of patients undergoing upper endoscopy without dilation. A total of 103 patients undergoing dilation and 50 control patients were studied; 22 of 103 patients (21%) undergoing dilation had at least one post-procedure blood culture positive for viridans streptococcus, compared with 1 of 50 (2%) of control patients (p = 0. 001). Blood cultures obtained 1 minute after stricture dilation were positive for viridans streptococcus in 19 of 81 (23%), in 16 of 96 (17%) 5 minutes post-dilation, and in 3 of 63 (5%) 20 to 30 minutes post-dilation. Of the 19 patients with viridans streptococcus bacteremia 1 minute after dilation, cultures were still positive in 14 of 19 (74%) at 5 minutes and in 2 of 19 (10%) 20 to 30 minutes post-dilation. These data support the use of antibiotic prophylaxis before esophageal stricture dilation for patients with valvular heart disease at risk for the development of infective endocarditis.


The predicted potential distribution of Aedes albopictus in China under the shared socioeconomic pathway (SSP)1-2.6.
Aedes albopictus (Skuse) (Diptera: Culicidae) is one of the 100 most invasive species in the world and represents a significant threat to public health. The distribution of Ae. albopictus has been expanding rapidly due to increased international trade, population movement, global warming and accelerated urbanization. Consequently, it is very important to know the potential distribution area of Ae. albopictus in advance for early warning and control of its spread and invasion. We randomly selected 282 distribution sites from 27 provincial-level administrative regions in China, and used the GARP and MaxEnt models to analyze and predict the current and future distribution areas of Ae. albopictus in China. The results showed that the current range of Ae. albopictus in China covers most provinces such as Yunnan and Guizhou Provinces, and the distribution of Ae. albopictus in border provinces such as Tibet, Gansu and Jilin Provinces tend to expand westwards. In addition, the potential distribution area of Ae. albopictus in China will continue to expand westwards due to future climate change under the SSP126 climate scenario. Furthermore, the results of environmental factor filtering showed that temperature and precipitation had a large effect on the distribution probability of Ae. albopictus.


Gliomas: new ways of treatment?
Evidence starts to appear that immune reactions may be important in the development and growth of gliomas. The purpose of this article is to review this evidence and to mention its implications for the future.


Influence of amino acids on the activity of cellulolytic enzymes obtained from spent medium of Fusarium cultures and on the "Cellulase S" Novo.
Comparative studies on the influence of 4 amino acids (cysteine, cystine, methionine and alanine) on the activity of enzymatic preparation were carried out. The action of the amino acids was shown to depend on pH, incubation time and the temperature of incubation. Attempts were made to find a correlation between the amino acids introduced and redox potential (Eh), pH and the activity of the cellulolytic enzymes. It was found that the addition of some amino acids to the reaction mixtures at different pH values affected the value of Eh -- which enhanced the cellulase activity.


Efficacy of the fully human monoclonal antibody MOR102 (#5) against intercellular adhesion molecule 1 in the psoriasis-severe combined immunodeficient mouse model.
Psoriasis is considered as a chronic immune-mediated disease characterized by inflammation and proliferation of the epidermis. Targeting intercellular adhesion molecule 1 (ICAM-1) is an attractive therapeutic option as this molecule is critically involved in leucocyte adhesion and extravasation as well as in lymphocyte activation. We have selected the fully human monoclonal antibody MOR102 (#5) against ICAM-1 from the Human Combinatorial Antibody Library (HuCAL). This antibody, as human IgG4 [corrected] was tested for its ability to interfere with lymphocyte activation and adhesion in vitro as well as for its antipsoriatic efficacy in vivo using the psoriasis-severe combined immunodeficient (SCID) mouse model. The antibody demonstrated efficient inhibition of lymphocyte adhesion to ICAM-1 in vitro, with an IC(50) of approximately 0.4 microg mL(-1) (3 nmol L(-1)). In addition, MOR102 (#5) reduced lymphocyte proliferation in mixed lymphocyte cultures by approximately 50%. The in vivo efficacy of MOR102 (#5) was tested on grafts derived from lesional skin of patients with chronic plaque-stage psoriasis transplanted on to SCID mice. Intraperitoneal injection of 10 mg kg(-1) of MOR102 (#5) antibody every alternate day over a period of 4 weeks resulted in reconstitution of orthokeratotic differentiation and a significant (P < 0.05) reduction in epidermal thickness as well as marked reduction in the inflammatory infiltrate. Therapeutic activity may be related to the targeting of ICAM-1 on keratinocytes and thus preventing efficient activation of local T cells. Based on the efficacy of the fully human monoclonal antibody MOR102 (#5) shown in vitro as well as in vivo in the psoriasis-SCID mouse model, initiation of clinical studies is indicated.


The Prevention of Positioning Injuries during Gynecologic Operations. Guideline of DGGG (S1-Level, AWMF Registry No. 015/077, February 2015).
Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Positioning injuries after lengthy gynecological procedures are rare, but the associated complications can be potentially serious for patients. Moreover, such injuries often lead to claims of malpractice and negligence requiring detailed medical investigation. To date, there are no binding evidence-based recommendations for the prevention of such injuries. Methods: This S1-guideline is the work of an interdisciplinary group of experts from a range of different professions who were commissioned by DGGG to carry out a systematic literature search of positioning injuries. Members of the participating scientific societies develop a consensus in an informal procedure. Afterwards the directorate of the scientific society approves the consensus. The recommendations cover.


Integrated ultracompact and broadband wavelength demultiplexer based on multi-component nano-cavities.
Integrated nanoscale photonic devices have wide applications ranging from optical interconnects and optical computing to optical communications. Wavelength demultiplexer is an essential on-chip optical component which can separate the incident wavelength into different channels; however, the experimental progress is very limited. Here, using a multi-component nano-cavity design, we realize an ultracompact, broadband and high-contrast wavelength demultiplexer, with 2.3 μm feature size, 200 nm operation bandwidth (from 780 nm to 980 nm) and a contrast ratio up to 13.7 dB. The physical mechanism is based on the strong modulation of the surface plasmon polaritons induced by the multi-component nano-cavities, and it can be generalized to other nanoscale photonic devices. This provides a strategy for constructing on-chip photon routers, and also has applications for chip-integrated optical filter and optical logic gates.


KRAS Addiction Promotes Cancer Cell Adaptation in Harsh Microenvironment Through Macropinocytosis.
KRAS is the most frequently mutated oncogene in cancer and despite intensive studies, attempts to develop effective therapies targeting KRAS or its downstream signaling have failed mostly due to the complexity of KRAS activation and function in cancer initiation and progression. Over the years, KRAS has been involved in several biological processes including cell survival, proliferation, and metabolism by promoting not only a favorable tumor environment but also a cell-microenvironment dialog to allow cancer cells to adapt to tumor microenvironment scarcity. One of the mechanisms involved in this adaption is KRAS-mediated macropinocytosis. Macropinocytosis is an evolutionarily conserved, large-scale, and nonselective form of endocytosis involving actin-driven cell membrane remodeling to engulf large amounts of extracellular fluids and proteins from the local environment. While macropinocytosis process has been known for decades, recent gain interest due to its regulation of KRAS-driven tumor growth in adverse microenvironments. By promoting extracellular protein and other macromolecules internalization, macropinocytosis provides a survival mechanism under nutrient scarce conditions and the potential for unrestricted tumor growth. Thus, a better understanding of macropinocytotic process is needed to develop alternative therapeutic strategies.


[Percutaneous drainage of recurrent peripancreatic fluid collections in acute pancreatitis. A case report].
The case of a 36 year old patient with acute pancreatitis is presented whose clinical course was dominated by extensive peripancreatic fluid exsudation and formation of cysts. Risky surgery in the acute phase of the disease could be avoided by ultrasonic guided percutaneous punction and placing of several, partly transhepatic, catheters. The fluid collections could be drained completely and showed no recurrence.


In vitro analysis of tau phosphorylation sites and its biological activity.
To explore the association between the abnormal phosphorylation sites found in Alzheimer disease (AD) tau and the inhibition of its biological activity. Ultracentrifugation, chromatography, manual Edman degradation and autosequence techniques were used to prepare and phosphorylate human recombinant tau, isolate and purify 32P tau peptides and determine phosphorylation sites. Phosphorylation of tau by casein kinase 1 (CK-1), cyclic AMP-dependent protein kinase (PKA) and glycogen synthetase kinase 3 (GSK-3) separately inhibited its biological activity and the inhibition of this activity by (CSK-3 was significantly increased if tau was prephosphorylated by CK-1 or PKA. The most potent inhibition was seen by a combined phosphorylation of tau with PKA and GSK-3. The treatment of tau by PKA and GSK-3 combination induced phosphorylation of tau at Ser-195, Ser-198, Ser-199, Ser-202, Thr-205, Thr-231, Ser-235, Ser-262, Ser-356, Ser-404, whereas Thr-181, Ser-184, Ser-262, Ser-356 and Ser-400 were phosphorylated by GSK-3 alone under the same condition. Phosphorylation of tau by PKA plus GSK-3 at Thr-205 might play a key role in tau pathology in AD.


Patellofemoral Joint Reconstruction for Patellar Instability: Medial Patellofemoral Ligament Reconstruction, Trochleoplasty, and Tibial Tubercle Osteotomy.
Recurrent patellar instability can be very debilitating and may require surgical intervention. A thorough workup must be completed in this subset of patients. Risk factors for recurrent instability include patella alta, trochlear dysplasia, an increased tibial tubercle-trochlear groove distance, and insufficiencies in the medial retinacular structures. Necessary treatment of these risk factors, once identified, should be addressed surgically. Patellofemoral reconstruction must be individually tailored to each patient's anatomy and may necessitate medial patellofemoral ligament reconstruction, tibial tubercle osteotomy, or trochleoplasty in any combination or as a standalone procedure. This article details our technique for surgical treatment of recurrent patellar instability with a medial patellofemoral ligament reconstruction, an open trochleoplasty, and a tibial tubercle osteotomy for patients with severe trochlear dysplasia, an increased tibial tubercle-trochlear groove distance, or patella alta.


Epithelial and mixed hepatoblastoma in the adult. Histological observations and general considerations.
Two instances of hepatoblastoma in adults are reported, with one case representing a purely epithelial, the other a mixed epithelio-mesenchymal variant. The purely epithelial tumour, consisting entirely of so-called fetal elements, was present in the liver of a 35-year-old woman without any other hepatic changes, whereas the mixed tumour developed in the coarsely nodular liver of a 73-year-old man with a currently inactive cirrhosis. Besides the epithelial component, this case held predominantly indifferent spindle-shaped and histiocytic mesenchymal cells which frequently gave rise to osteoid and to bony trabeculae, and on occasion also to vascular structures, biliary ducts and even to groups of hepatocytes. The cytological and histological picture of both cases is comparable even in its details to that seen in the hepatoblastomas of early childhood. This concordance should be insisted upon as a diagnostic pre-condition if a mixed tumour in the adult, consisting of several components, is to be accepted as a hepatoblastoma. This similarity also enables us to recognize the purely epithelial variant of the hepatoblastoma in the older patient as belonging to this tumour category, and to separate it from other hepatic carcinomas. It is suggested that in these tumours the pluripotent cells, or the cells that have again become pluripotent, are derived from differentiated hepatocytes; no evidence in favour of the existence of a particular cellular subpopulation or of "stem cells" has been found.


Risk profile analysis of uncomplicated type B aortic dissection patients undergoing thoracic endovascular aortic repair: Laboratory and radiographic predictors.
There is emerging evidence to support pre-emptive thoracic endovascular aortic repair (TEVAR) intervention for uncomplicated type B aortic dissection (unTBAD). Pre-emptive intervention would be particularly beneficial in patients that have a higher baseline risk of progressing to complicated TBAD (coTBAD). There remain debate on the optimal clinical, laboratory, morphological, and radiological parameters, which would identify the highest-risk patients that would benefit most from pre-emptive TEVAR. This review summarizes evidence on the clinical, laboratory, and morphological parameters that increase the risk profiles of unTBAD patients. A comprehensive literature search was carried out on multiple electronic databases including PubMed, EMBASE, Ovid, and Scopus to collate all research evidence on the clinical, laboratory, and morphological parameters that increase the risk profiles of unTBAD patients RESULTS: At present, there are no clear clinical guidelines using risk-stratification to inform the selection of unTBAD patients for TEVAR. However, there are noticeable literature trends that can assist with the identification of the most at-risk unTBAD patients. Patients are at particular risk when they have refractory pain and/or hypertension, elevated C-reactive protein (CRP), larger aortic diameter, and larger entry tears. These risks should be considered alongside factors that increase the procedural risk of TEVAR to create a well-balanced approach. Advances in biomarkers and imaging are likely to identify more pertinent parameters in the future to optimize the development of balanced, risk-stratified treatment protocols. There are a variety of risk profiling parameters that can be used to identify the high-risk unTBAD patient, with novel biomarkers and imaging parameters emerging. Longer-term evidence verifying these parameters would be ideal. Further randomized controlled trials and multicentre registry analyses are also warranted to guide risk-stratified selection protocols.


Leuprolide acetate and intravascular leiomyomatosis.
Intravascular leiomyomatosis is an uncommon uterine tumor characterized by grossly visible intravascular proliferation of benign smooth muscle. Based on its role in reducing the size of leiomyomas, leuprolide acetate was given as induction therapy for extensive inoperable intravascular leiomyomatosis. A 44-year-old woman, gravida 1, para 1-0-0-1, presented in July 1992 with abnormal uterine bleeding. Pelvic examination and ultrasonography revealed the presence of a large irregular pelvic mass. At laparotomy, uterine and bilateral adnexal masses were noted extending up to the pelvic inlet and into the broad and infundibulopelvic ligaments. This tumor was not resectable. Based on histologic and immunoperoxidase studies, the lesion was interpreted as a plexiform epithelioid smooth-muscle tumor of uncertain malignant potential. Leuprolide acetate depot therapy (7.5 mg every 4 weeks) was begun in September 1992 and continued for a total of 20 months. Maximal tumor regression was achieved after 9 months. Subsequent reexploration at 20 months revealed a resectable tumor. Resection was accomplished successfully, leaving no apparent residual disease. Leuprolide acetate induced tumor regression and rendered debulking surgery feasible in a patient with previously unresectable, widespread, retroperitoneal intravascular leiomyomatosis. Primary hormone therapy may provide alternative therapeutic options for certain cases of intravascular leiomyomatosis.


Relationship between idiopathic sudden sensorineural hearing loss and subsequent stroke.
The correlation between idiopathic sudden sensorineural hearing loss and subsequent stroke is unclear. This study aimed to review stroke incidence after idiopathic sudden sensorineural hearing loss among patients admitted to a tertiary referral center and aimed to compare the characteristics of patients with and without stroke. Individual retrospective cohort study. Between January 2000 and April 2004, a total of 349 patients diagnosed with idiopathic sudden sensorineural hearing loss were admitted to Taipei Veterans General Hospital and followed up until May 31, 2009. The patients were divided into two groups: a stroke group and a nonstroke group. Cox proportional hazards regression was used for analysis after adjusting for age, sex, hypertension, diabetes mellitus, coronary artery disease, and prior stroke history. The average follow-up duration was 81.7 ± 15.0 months, and the average annual stroke incidence rate was 0.6%. The number of patients with older age, hypertension, coronary artery disease, and prior stroke history was significantly higher in the stroke group than in the nonstroke group. Prior stroke history was the most important risk factor for stroke after idiopathic sudden sensorineural hearing loss. Idiopathic sudden sensorineural hearing loss did not increase stroke risk. The average annual stroke incidence rate after idiopathic sudden sensorineural hearing loss was comparable with that in the general Taiwanese population. The study patients experienced stroke because they carried the risk factors for stroke. In patients with modified risk factors for stroke, efforts should be made to prevent stroke rather than idiopathic sudden sensorineural hearing loss.


[Analysis of distalization of lower canine by light-segmented archwire].
To analyze the practical effect of distalization of lower cuspiud by light-segmented archwire. 17 cases were selected. In all cases, two lower first bicuspids were extracted and lower molars were designed as reinforced anchorage. In the first half year, lower cuspids were distalized with light-segmented archwire, and lower incisors were in the physiologic drift stage. Before the treatment, three months and six months after the treatment, cephalograms and study models were recorded respectively. The data were analyzed with SPSS 10.0. The distance of mesiolization of the first lower molar was 1.14 mm in half a year. The distance of distalization of the lower cuspid was 5.02 mm in half a year. No significant difference was found in LM-MP and SN-MP angle. LI-NB angle was decreased by 9.57 degrees. Crowding of lower incisors was transferred from -2.55 mm to 1.08 mm. During distalization of lower cuspid by light-segmented archwire, anchorage tooth was stable, lower cuspids were distalized effectively, and lower incisors drifted towards the ideal position automatically.


Advanced stereoscopic projection technology significantly improves novice performance of minimally invasive surgical skills.
Three-dimensional (3D) surgical imaging systems provide stereoscopic depth cues that are lost in conventional two-dimensional (2D) display systems. Recent improvements in stereoscopic projection technology using passive polarising displays may improve performance of minimally invasive surgical skills. This study aims to identify the effect of passive polarising stereoscopic displays on novice surgeon performance of minimally invasive surgical skills. 20 novice surgeons performed 10 repetitions of 4 surgical skills tasks using a new passive polarising stereoscopic display under 3D and 2D conditions. The previously validated tasks used were rope pass, paper cut, needle capping and knot tying. Outcome measures included total error rate and time for task completion. Novice surgeons demonstrated a significant reduction in error rates for sequential repetitions of each task using the passive polarising stereoscopic display compared with the 2D display. Mean errors for the 3D versus the 2D mode were 2.0 versus 4.3 for rope pass (P ≤ 0.001), 0.8 versus 1.6 for paper cut (P = 0.001), 1.3 versus 4.2 for needle capping (P ≤ 0.001) and 2.8 versus 8.0 for knot tying (P ≤ 0.001). Novice surgeons demonstrated a significant improvement in mean time for completion for all four tasks when using the 3D system. Mean time (in seconds) for 3D versus 2D were 106.5 versus 134.4 for rope pass (P ≤ 0.001), 116.1 versus 176.3 for paper cut (P ≤ 0.001), 76.3 versus 141.6 for needle capping (P ≤ 0.001) and 153.4 versus 252.6 for knot tying (P ≤ 0.001). Passive polarising stereoscopic displays significantly improve novice surgeon performance during acquisition of minimally invasive surgical skills.


ASAS-EGB: A statistical framework for estimating allele-specific alternative splicing events using transcriptome data.
Ubiquitous Alternative splicing (AS) in eukaryotes greatly increases the biodiversity of proteins and involves in disease and cancer. Allele-specific AS studies can facilitate the identification of cis-acting elements because both alleles share the same cellular environment. Due to the limited information provided on the exons defined by AS events, we propose a statistical framework and algorithm ASAS-EGB for ASAS analysis using the gene transcriptome. The framework obtains exclusively compatible sets of gene isoforms supporting each event isoform, and uses both phased and non-phased SNPs within the exons on the gene isoforms for inference. Using this strategy, we have demonstrated ASAS-EGB can yield better ASAS inferential performance than using event isoforms. ASAS-EGB supports both single-end and paired-end RNA-seq data, and we have proved its robustness using RNA-seq replicates of individual NA12878. ASAS-EGB builds Bayesian models for ASAS analysis, and the MCMC method is used to solve the problem. With more detailed annotations for individual genomes and transcriptomes appearing in the future, the algorithm proposed by the paper can provide better support for these data to reveal the regulatory mechanisms of individual genomes.


Binding differences of human and amphibian corticotropin-releasing factor type 1 (CRF(1)) receptors: identification of amino acids mediating high-affinity astressin binding and functional antagonism.
The corticotropin-releasing factor (CRF) type 1 receptors (CRF(1)) from human (hCRF(1)) and Xenopus (xCRF(1)) differ from one another by their agonist- and antagonist-binding preference. While the agonist-binding site of the xCRF(1) receptor has been mapped, the amino acids that mediate binding of the potent peptide antagonist astressin are unknown. By constructing receptor chimeras followed by site-directed mutagenesis, the astressin-binding site of the xCRF(1) receptor was located between residues 76 and 83. This region partially overlaps with the agonist-selective domain of the xCRF(1) receptor (residues 76-89). Mutagenesis of the amphibian residues Gln(76), Gly(81) and Val(83) to the human sequence (Arg(76)Asn(81)Gly(83)) generated a receptor mutant that bound astressin with even higher affinity than the native hCRF(1) receptor. An amino acid doublet (Glu(70)Tyr(71)) that is conserved in the xCRF(1) and hCRF(2(a)) receptor after incorporation into the hCRF(1) receptor sequence was found to facilitate antagonist binding up to 15-fold higher. In agreement with the binding data, astressin was a more potent functional antagonist at receptors expressing the Glu(70)Tyr(71) motif. These data show that the agonist- and antagonist-binding sites of the hCRF(1) receptor partially overlap and that two amino acids within the N terminus of the hCRF(1) receptor negatively influence binding and functional antagonism of astressin.


The abdominal compartment syndrome is a morbid complication of postinjury damage control surgery.
The abdominal compartment syndrome (ACS) is a recognized complication of damage control surgery (DCS). The purposes of this study were to (1) determine the effect of ACS on outcome after DCS, (2) identify patients at high risk for the development of ACS, and (3) determine whether ACS can be prevented by preemptive intravenous bag closure during DCS. Patients requiring postinjury DCS at our institution from January 1996 to June 2000 were divided into groups depending on whether or not they developed ACS. ACS was defined as an intra-abdominal pressure (IAP) greater than 20 mm Hg in association with increased airway pressure or impaired renal function. ACS developed in 36% of the 77 patients who underwent DCS with a mean IAP prior to decompression of 26 +/- 1 mm Hg. The ACS versus non-ACS groups were not significantly different in patient demographics, Injury Severity Score, emergency department vital signs, or intensive care unit admission indices (blood pressure, temperature, base deficit, cardiac index, lactate, international normalized ratio, partial thromboplastin time, and 24-hour fluid). The initial peak airway pressure after DCS was higher in those patients who went on to develop ACS. The development of ACS after DCS was associated with increased ICU stays, days of ventilation, complications, multiorgan failure, and mortality. ACS after postinjury DCS worsens outcome. With the exception of early elevation in peak airway pressure, we could not identify patients at higher risk for ACS; moreover, preemptive abdominal bag closure during initial DCS did not prevent this highly morbid complication.


Arabidopsis PDI11 interacts with lectin molecular chaperons calreticulin 1 and 2 through its D domain.
The endoplasmic reticulum (ER) is equipped with protein disulfide isomerases (PDIs), molecular chaperons, and other folding enzymes to ensure that newly synthesized proteins in the ER are properly folded. Molecular chaperons and PDIs can form complex to promote protein folding in the ER of mammalian cells. In plants, many PDIs associate with each other and function cooperatively in oxidative protein folding. As a plant unique protein disulfide isomerase, Arabidopsis thaliana PDI11 (AtPDI11) demonstrates oxidative protein folding activities and works synergistically with AtPDI2/5. However, whether AtPDI11 associates with molecular chaperons or AtPDIs in catalyzing disulfide formation remained unknown. Here, we find that AtPDI11 interacts with ER resident lectin chaperones calreticulin 1 (CRT1) and CRT2. Furthermore, the D domain, but not the a or a' domain of AtPDI11 provides the biding sites for its interaction with CRT1/2. Moreover, the P domain of CRT1 is responsible for its interaction with AtPDI11. Our work implies that Arabidopsis CRT1/2 may specifically recruit AtPDI11 to assist the folding of glycoproteins in the ER.