A generalized machine-learning aided method for targeted identification of industrial enzymes from metagenome: A xylanase temperature dependence case study.
Growing industrial utilization of enzymes and the increasing availability of metagenomic data highlight the demand for effective methods of targeted identification and verification of novel enzymes from various environmental microbiota. Xylanases are a class of enzymes with numerous industrial applications and are involved in the degradation of xylose, a component of lignocellulose. The optimum temperature of enzymes is an essential factor to be considered when choosing appropriate biocatalysts for a particular purpose. Therefore, in silico prediction of this attribute is a significant cost and time-effective step in the effort to characterize novel enzymes. The objective of this study was to develop a computational method to predict the thermal dependence of xylanases. This tool was then implemented for targeted screening of putative xylanases with specific thermal dependencies from metagenomic data and resulted in the identification of three novel xylanases from sheep and cow rumen microbiota. Here we present thermal activity prediction for xylanase, a new sequence-based machine learning method that has been trained using a selected combination of various protein features. This random forest classifier discriminates non-thermophilic, thermophilic, and hyper-thermophilic xylanases. The model's performance was evaluated through multiple iterations of sixfold cross-validations as well as holdout tests, and it is freely accessible as a web-service at arimees.com.


Association between the Glu298Asp and 4b/4a polymorphisms of endothelial nitric oxide synthase and coronary slow flow in the North Indian population.
Genetic variants in endothelial nitric oxide synthase gene (NOS3) leading to endothelial dysfunction may be predispose to the coronary slow-flow phenomenon (CSFP). In this study, we examined the relationship between Glu298Asp (894G/T) and 4b/4a polymorphisms of NOS3 and CSFP. A total of 27 patients with CSFP but otherwise normal coronary arteries (mean age 50.4±8.2 years) and 200 controls with a normal coronary angiogram (mean age 53.1±8.6 years) were screened for Glu298Asp and 4b/4a polymorphisms by restriction fragment length polymorphism and PCR, respectively. Nitric oxide levels were determined using Griess' enzymatic method for an association with the polymorphisms. The genotype distribution of the Glu298Asp polymorphism differed significantly between the CSFP patients and controls (P=0.004). The dominant genetic model showed that GT+TT was significantly prevalent in patients in comparison with controls (P=0.014) and the T allele was significantly prevalent in patients (P=0.002). The genetic distribution of 4b/4a differed significantly for the heterozygous genotype ba (P=0.047). The overdominant genetic model re-established that the ba genotype was significantly prevalent in patients (P=0.044). Nitric oxide level was higher in patients than in controls, the values being 144.51±43.25 and 129.64±29.47 μmol/l, respectively (P>0.05). The genotypes of Glu298Asp showed a trend of association with nitric oxide levels, which decreased linearly in the order of GG, GT, and TT (P>0.05). The Glu298Asp polymorphism of NOS3 associates with CSFP.


Long-term follow-up of ifosfamide renal toxicity in children treated for malignant mesenchymal tumors: an International Society of Pediatric Oncology report.
The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.


Tuning of Peptide Cytotoxicity with Cell Penetrating Motif Activatable by Matrix Metalloproteinase-2.
Although diverse cell penetrating motifs not only from naturally occurring proteins but also from synthetic peptides have been discovered and developed, the selectivity of cargo delivery connected to these motifs into the desired target cells is generally low. Here, we demonstrate the selective cytotoxicity tuning of an anticancer KLA peptide with a cell penetrating motif activatable by matrix metalloproteinase-2 (MMP2). The anionic masking sequence introduced at the end of the KLA peptide through an MMP2-cleavable linker is selectively cleaved by MMP2 and the cationic cell penetrating motif is activated. Upon treatment of the peptide to H1299 cells (high MMP2 level), it is selectively internalized into the cells by MMP2, which consequently induces membrane disruption and cell death. In contrast, the peptide shows negligible cytotoxicity toward A549 cancer cells with low MMP2 levels. Furthermore, the selective therapeutic efficacy of the peptide induced by MMP2 is also corroborated using in vivo study.


Hepcidin in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common reasons for cancer-related deaths. Excess iron increases HCC risk. Inevitably, hepcidin, the iron hormone that maintains systemic iron homoeostasis is involved in HCC pathology. Distinct from other cancers that show high hepcidin expression, HCC patients can show low hepcidin levels. Thus, it is of immense clinical benefit to address the regulation and action of hepcidin in HCC as this may help in identifying molecular targets for diagnosis, prognosis, and therapeutics. Accordingly, this review explores hepcidin in HCC. It presents the levels of tissue and serum hepcidin and explains the mechanisms that contribute to hepcidin reduction in HCC. These include downregulation of HAMP, TfR2, HJV, ALK2 and circular RNA circ_0004913, upregulation of matriptase-2 and GDF15, inactivation of RUNX3 and mutation in TP53. The enigmas around mir-122 and the functionalities of two major hepcidin inducers BMP6 and IL6 in relation to hepcidin in HCC are discussed. Effects of hepcidin downregulation are explained, specifically, increased cancer proliferation via activation of CDK1/STAT3 pathway and increased HCC risk due to reduction in a hepcidin-mediated protective effect against hepatic stellate cell activation. Hepcidin-ferroportin axis in HCC is addressed. Finally, the role of hepcidin in the diagnosis, prognosis and therapeutics of HCC is highlighted.


Taxonomic revision of Trypanidius Blanchard, 1846 in South America (Insecta: Coleoptera: Cerambycidae).
The genus Trypanidius Blanchard, 1846 includes 15 species in the Neotropical Region, nine of which occur in South America. In this contribution, the genus and South American species are redescribed and Trypanidius mimicavus sp. nov. is described from Bolivia. New distributional data are given for T. andicola Blanchard, 1846; T. dimidiatus Thomson, 1860; and T. notatus (Fabricius, 1787). All species are illustrated and a key to all species is provided.


Does azurin bind to the transactivation domain of p53? A Trp phosphorescence study.
The bacterial redox protein azurin has been shown to be able to enter into cancer cells and induce apoptosis by stabilizing p53. Although the formation of a complex between the two proteins has been demonstrated, little is known about their binding features. We investigated the interaction between the transcription activation domain of p53 (p53(1-63)) and Pseudomonas aeruginosa azurin using fluorescence and phosphorescence spectroscopic techniques. Trp phosphorescence lifetime measurements revealed conformational changes in azurin induced by the interaction with p53(1-63). Acrylamide quenching of Trp phosphorescence also indicated a significant increase in the overall flexibility of azurin upon binding to p53(1-63). We show that azurin binds to the N-terminal region of p53 with a dissociation constant in the 5-10 μM range. No change in the fluorescence and phosphorescence emission of p53(1-63) was detected in the presence of azurin. This result indicated that no Trp residue of p53(1-63) is located in the interaction site with azurin and therefore suggested that the azurin binding site does not overlap that of MDM2, the protein that plays a crucial role in the p53 regulation. The present results may assist in the design of novel cancer treatments based on p53 stabilization by azurin.


Massive hepatic infarction in preeclampsia: successful treatment with continuous hemodiafiltration and corticosteroid therapy.
Massive hepatic infarction associated with pregnancy is extremely rare, but is potentially fatal. A 35-year-old primigravida with mild preeclampsia developed acute right upper quadrant pain and marked elevation of liver enzymes at 26 weeks' gestation. After emergent cesarean section, her condition was complicated by oliguric renal failure and pulmonary edema with further deterioration of hepatic function (aspartate transaminase 4339 IU/L; alanine transaminase 3489 IU/L; lactate dehydrogenase 10780 IU/L). The contrast-enhanced computed tomography revealed non-enhancing low attenuation throughout the right lobe of liver, compatible with infarction. Continuous hemodiafiltration was initiated as renal support on postpartum day one. However, excessive fluid accumulation persisted, and she developed severe edema formation in both lung and systemic body surface. To ameliorate microvascular endothelial injury, corticosteroid therapy was begun on postpartum day five. Following treatment initiation, her renal and hepatic function showed steady improvement, accompanied by drastic resolution of edema formation. She was discharged five weeks postpartum with no additional treatment, and is without sequelae six months later. Massive hepatic infarction should be considered in preeclamptic patients who present acute abdominal pain and severe hepatic dysfunction, and continuous hemodiafiltration with corticosteroid therapy may improve the maternal outcome.


Tailoring Cardiac Synthetic Transcriptional Modulation Towards Precision Medicine.
Molecular and genetic differences between individual cells within tissues underlie cellular heterogeneities defining organ physiology and function in homeostasis as well as in disease states. Transcriptional control of endogenous gene expression has been intensively studied for decades. Thanks to a fast-developing field of single cell genomics, we are facing an unprecedented leap in information available pertaining organ biology offering a comprehensive overview. The single-cell technologies that arose aided in resolving the precise cellular composition of many organ systems in the past years. Importantly, when applied to diseased tissues, the novel approaches have been immensely improving our understanding of the underlying pathophysiology of common human diseases. With this information, precise prediction of regulatory elements controlling gene expression upon perturbations in a given cell type or a specific context will be realistic. Simultaneously, the technological advances in CRISPR-mediated regulation of gene transcription as well as their application in the context of epigenome modulation, have opened up novel avenues for targeted therapy and personalized medicine. Here, we discuss the fast-paced advancements during the recent years and the applications thereof in the context of cardiac biology and common cardiac disease. The combination of single cell technologies and the deep knowledge of fundamental biology of the diseased heart together with the CRISPR-mediated modulation of gene regulatory networks will be instrumental in tailoring the right strategies for personalized and precision medicine in the near future. In this review, we provide a brief overview of how single cell transcriptomics has advanced our knowledge and paved the way for emerging CRISPR/Cas9-technologies in clinical applications in cardiac biomedicine.


Student perceptions about interprofessional education after an elective course.
A growing body of evidence indicates interprofessional collaborative practice improves patient care. With this in mind, Louisiana State University Health Sciences Center formally committed to expanding interprofessional education (IPE) initiatives. Thirty-eight self-selected students enrolled in an IPE elective course during the fall of 2012. Students completed the Readiness for Interprofessional Learning Scale (RIPLS) pre- and post-course and also completed a post-course survey. Results indicated a significant change in the roles and responsibilities scale of the RIPLS. Analysis of the data from the post-course survey demonstrated students were able to identify key terms of an IPE definition, as related to their learning experience. In addition, themes of communication, learning/increased knowledge, and collaboration/contribution of other health care professionals were noted across all questions in the post-course survey. Based on the results of this study, an elective course is a promising educational opportunity to increase awareness and knowledge of IPE within academic medical centers.


[Cholagenic diarrhea is a type of postcholescystectomy syndrome].
To study the role of biliary acids (BAs) in the pathogenesis of chronic diarrhea (CD) in patients undergoing cholecystectomy (CE). Twenty-five patients with post-CE diarrhea were examined. A comparison group consisted of 11 patients with diarrhea-predominant irritable bowel syndrome (IBS). The results of an examination of 15 healthy individuals were taken as normal values. Daily fecal BAs were determined by an enzyme spectrophotometric technique. In the patients after CE, daily fecal BA losses were found to be thrice as large as that in the healthy individuals. In the comparison group of patients with IBS, fecal bile excretion was not greater than the normal values. Stool normalization with a simultaneous decrease in fecal BA losses was seen in 92% of the post-CE patients receiving a course of therapy with adsorbents and astringents. Post-CE CD is a type of postcholescystectomy syndrome.


Lipid profiles for etravirine versus efavirenz in treatment-naive patients in the randomized, double-blind SENSE trial.
Etravirine is approved for use in treatment-experienced patients at a dose of 200 mg twice daily. Efavirenz has been associated with greater increases in serum lipids compared with other non-nucleosides in randomized trials of first-line treatment. In this double-blind, placebo-controlled trial, 157 treatment-naive patients with HIV RNA >5000 copies/mL were randomized 1:1 to either 400 mg of etravirine once daily (n=79) or 600 mg of efavirenz once daily (n=78) plus two nucleoside analogues (either abacavir/lamivudine, zidovudine/lamivudine or tenofovir/emtricitabine) for 48 weeks. Lipids were measured under fasting conditions at baseline and all visits to Week 48. Clinicaltrials.gov identifier: NCT00903682. Overall, the patients had a median baseline CD4 count of 302 cells/mm(3) (range 74-722) and a median HIV RNA of 4.8 log(10) copies/mL (range 3.5-6.6). Both the non-nucleosides and the nucleoside analogues used caused changes in serum lipids. In the efavirenz arm, patients showed significantly larger increases in high-density lipoprotein (HDL) (+0.15 mmol/L, P=0.004), low-density lipoprotein (LDL) (+0.35 mmol/L, P=0.005), total cholesterol (+0.61 mmol/L, P<0.0001) and triglycerides (+0.33 mmol/L, P=0.03) at Week 48 compared with the etravirine arm. Across the two arms, patients taking abacavir/lamivudine showed greater increases in total cholesterol (+0.47 mmol/L, P=0.005) compared with patients taking tenofovir/emtricitabine. There were fewer grade 3/4 elevations in total cholesterol, LDL and triglycerides in the etravirine arm (2 patients, 1 patient and 0 patients, respectively) versus the efavirenz arm (8 patients, 6 patients and 2 patients, respectively). In the SENSE trial, first-line treatment with 400 mg of etravirine once daily plus two nucleoside analogues led to fewer grade 3 or 4 lipid elevations compared with efavirenz plus two nucleoside analogues.


Efficacy of a prospective community-based intervention to prevent preterm birth.
To evaluate a community-based intervention trial for the prevention of preterm birth. This trial was conducted on pregnant women in the Amakusa area, and in the Hitoyoshi-Kuma area, both in Japan. Prophylactic oral antibiotics were recommended for pregnant women with high-risk on preterm birth. The subjects were also encouraged to undergo a periodontal examination. An explanation of proper tooth brushing was given and full mouth scaling was allowed if deemed necessary. Of 720 consented subjects in the Amakusa area and of 373 in the Hitoyoshi-Kuma area, bacterial vaginosis was found in 100 (13.9%) Amakusa residents and 71 (19.0%) Hitoyoshi-Kuma residents. Prophylactic antibiotics were prescribed for 93 Amakusa residents and 39 Hitoyoshi-Kuma residents. Among subjects who underwent a periodontal examination, periodontal disease was found in 47.7% of Amakusa residents and 59.7% of Hitoyoshi-Kuma residents. Periodontal health was improved among these women by a nonsurgical intervention during their pregnancy. Comparing the incidences of very low birth weight (VLBW) with the averages during the preceding 6 years in each area, the incidences of VLBW was 46.4% lower in Amakusa and 69.7% Hitoyoshi-Kuma during the study year. A community-based multifaceted intervention might reduce the incidence of VLBW infants.


Increased long-term survival of posterior cruciate-retaining versus posterior cruciate-stabilizing total knee replacements.
Considerable debate remains regarding the use of posterior cruciate-retaining or posterior cruciate-stabilizing designs for total knee arthroplasty. Multiple studies have investigated kinematic, radiographic, and clinical outcomes of both. Nevertheless, long-term survivorship analyses directly comparing the two designs have not been performed, to our knowledge. Our goal was to analyze the fifteen-year survival of posterior cruciate-retaining and posterior cruciate-stabilizing total knee replacements at our institution. A retrospective review identified 8117 total knee arthroplasties (5389 posterior cruciate-retaining and 2728 posterior cruciate-stabilizing) that had been performed from 1988 to 1998. This range was chosen because both designs were used in high volumes at our institution during this period. Patients were followed via our total joint registry at one, two, and five years after the arthroplasty and every five years thereafter. Aseptic revision surgery was the primary end point of our analysis. Implant survival was estimated with Kaplan-Meier curves. Survival at fifteen years was 90% for posterior cruciate-retaining total knee replacements, compared with 77% for posterior cruciate-stabilizing total knee replacements (p < 0.001). In knees with preoperative deformity, the fifteen-year survival was 90% for posterior cruciate-retaining total knee replacements, compared with 75% for posterior cruciate-stabilizing total knee replacements (p < 0.04). Likewise, in knees without preoperative deformity, the fifteen-year survival was 88% for posterior cruciate-retaining total knee replacements, compared with 78% for posterior cruciate-stabilizing total knee replacements (p < 0.001). After adjustment for age, sex, preoperative diagnosis, and preoperative deformity, the risk of revision was significantly lower in knees with a posterior cruciate-retaining total knee replacement (p < 0.001; hazard ratio = 0.5; 95% confidence interval, 0.4 to 0.6). In evaluating the implants used at our institution for total knee arthroplasty during the study period, posterior cruciate-retaining prostheses had significantly improved survival in comparison with posterior cruciate-stabilizing prostheses at fifteen years. Furthermore, this significant difference remained when accounting for age, sex, diagnosis, and deformity.


RASSF1A-Mediated Suppression of Estrogen Receptor Alpha (ERα)-Driven Breast Cancer Cell Growth Depends on the Hippo-Kinases LATS1 and 2.
Around 70% of breast cancers express the estrogen receptor alpha (ERα). This receptor is of central importance for breast cancer development and estrogen-dependent tumor growth. However, the molecular mechanisms that are responsible for the control of ERα expression and function in the context of breast carcinogenesis are complex and not fully understood. In previous work, we have demonstrated that the tumor suppressor RASSF1A suppresses estrogen-dependent growth of breast cancer cells through a complex network that keeps ERα expression and function under control. We observed that RASSF1A mediates the suppression of ERα expression through modulation of the Hippo effector Yes-associated protein 1 (YAP1) activity. Here we report that RASSF1A-mediated alteration of YAP1 depends on the Hippo-kinases LATS1 and LATS2. Based on these results, we conclude that inactivation of RASSF1A causes changes in the function of the Hippo signaling pathway and altered activation of YAP1, and as a consequence, increased expression and function of ERα. Thus, the inactivation of RASSF1A might constitute a fundamental event that supports the initiation of ERα-dependent breast cancer. Furthermore, our results support the notion that the Hippo pathway is important for the suppression of luminal breast cancers, and that the tumor-suppressor function of RASSF1A depends on LATS1 and LATS2.


Modafinil as adjunctive therapy in depressed outpatients.
The wake-promoting agent modafinil (PROVIGIL) may prove useful as an adjunctive treatment in patients with suboptimal responses to antidepressant regimens. This retrospective chart review describes the use of modafinil as an adjunct to antidepressant therapy in 78 outpatients in a general psychiatric practice and discusses in detail treatment outcomes for 3 patients. Statistically significant improvements in mean Carroll Depression Rating Scale scores (p < 0.01), Visual Analog Scale scores for overall feeling (p < 0.003), and Clinical Global Impression of Severity ratings (p < 0.001) were demonstrated following treatment with modafinil. Treatment with modafinil rapidly improved wakefulness, fatigue, and everyday functioning in individual cases. Modafinil was well tolerated in combination with antidepressants and other medications. These findings suggest that adjunctive modafinil may improve treatment outcomes when used with antidepressant therapy in depressed patients, particularly in those with problematic sleepiness or fatigue.


Development of Realistic Striatal Digital Brain (SDB) Phantom for 123I-FP-CIT SPECT and Effect on Ventricle in the Brain for Semi-quantitative Index of Specific Binding Ratio.
This study aimed at developing the realistic striatal digital brain (SDB) phantom and to assess specific binding ratio (SBR) for ventricular effect in the 123I-FP-CIT SPECT imaging. SDB phantom was constructed in to four segments (striatum, ventricle, brain parenchyma, and skull bone) using Percentile method and other image processing in the T2-weighted MR images. The reference image was converted into 128×128 matrixes to align MR images with SPECT images. The process image was reconstructed with projection data sets generated from reference images additive blurring, attenuation, scatter, and statically noise. The SDB phantom was evaluated to find the accuracy of calculated SBR and to find the effect of SBR with/without ventricular counts with the reference and process images. We developed and investigated the utility of the SDB phantom in the 123I-FP-CIT SPECT clinical study. The true value of SBR was just marched to calculate SBR from reference and process images. The SBR was underestimated 58.0% with ventricular counts in reference image, however, was underestimated 162% with ventricular counts in process images. The SDB phantom provides an extremely convenient tool for discovering basic properties of 123I-FP-CIT SPECT clinical study image. It was suggested that the SBR was susceptible to ventricle.


Use of chemometric methodology in optimizing conditions for competitive binding partial filling affinity capillary electrophoresis.
This work expands the knowledge of the use of chemometric response surface methodology (RSM) in optimizing conditions for competitive binding partial filling ACE (PFACE). Specifically, RSM in the form of a Box-Behnken design was implemented in flow-through PFACE (FTPFACE) to effectively predict the significance of injection time, voltage, and neutral ligand (neutral arylsulfonamide) concentration, [L(o)], on protein-neutral ligand binding. Statistical analysis results were used to create a model for response surface prediction via contour and surface plots at a given maximum response (DeltaRMTR) to reach a targeted K(b) = 2.50 x 10(6) M(-1). The adequacy of the model was then validated by experimental runs at the optimal predicted solution (injection time = 2.3 min, voltage = 11.6 kV, [L(o)] = 1.4 microM). The achieved results greatly extend the usefulness of chemometrics in ACE and provide a valuable statistical tool for the study of other receptor-ligand combinations.


Interglial cell gap junctions increase in urethane-induced photoreceptor degeneration in rats.
Gap junctions are found between astrocytes in the inner retina of normal rats, but they are rare between Müller cells or between astrocytes and Müller cells in the inner retina. After photoreceptor degeneration induced by urethane treatment of newborn animals, morphologic alterations of glial cells occur in the inner retina. The Müller cells withdraw from the inner limiting membrane, and the astrocytes hypertrophy and occupy the vitread surface of the inner limiting membrane. The frequency and size of the gap junctions between astrocytes increases with time in rats with urethane-induced photoreceptor degeneration, to a greater extent than expected from elaboration of additional astrocyte plasma membrane. The gap junction-profile length per glial cell membrane-contact length is 2.8 +/- 1.1 microns/1000 microns of membrane in 8-week-old normal animals; it increases to 18.9 +/- 9.4 microns/1000 microns of membrane at 56 weeks of age in urethane-treated animals. The average size of the gap junction-profile length doubles during this same period. To the authors' knowledge this is the first study demonstrating pathologic changes in gap junctions in central nervous system tissue. The authors speculate that this up-regulation of gap junctions occurs in response to an altered extracellular ionic composition in an attempt to increase the lateral spatial buffering of K+ by these cells. The relative location of glial cells in retina can determine, in part, the vulnerability of the retina to edema.


Tires as larval habitats for mosquitoes (Diptera: Culicidae) in southern Manitoba, Canada.
In 2003, a survey at waste management grounds and tire dealerships was conducted to determine the species composition of mosquitoes in tires in southern Manitoba, Canada. Over 25% of the 1,142 tires sampled contained a total of 32,474 mosquito larvae and pupae. Culex restuans made up at least 95% of the larvae collected for each month of the summer. Culiseta inornata and Culex tarsalis reached their greatest numbers in July and August, respectively, though they were never abundant. Ochlerotatus triseriatus was also found but never reached more than 1% of the total larvae collected in any given month. Mosquito prevalence was more than three times greater in August (36.1%) than in June (11.7%). Orientation affected prevalence of mosquitoes in tires: 31.4% of vertical tires (tires standing on their treads) contained mosquitoes, whereas mosquitoes were found in only 18.9% of horizontal tires (tires parallel to the ground). Tires in the eastern region of Manitoba contained mosquitoes more often (61.7%), irrespective of date, than Winnipeg (25.9%), the central region (29.1%), or the western region (19.8%). Mosquito prevalence was similar across three size categories of tires, car tires (18.8%), truck tires (19.8%), and semi-trailer tires (26.7%), though tractor tires (47.8%) contained significantly more mosquitoes than tires in the other categories.


Nanomechanical analysis of pigmented human melanoma cells.
Based on hitherto measurements of elasticity of various cells in vitro and ex vivo, cancer cells are generally believed to be much softer than their normal counterparts. In spite of significant research efforts on the elasticity of cancer cells, only few studies were undertaken with melanoma cells. However, there are no reports concerning pigmented melanoma cells. Here, we report for the first time on the elasticity of pigmented human melanoma cells. The obtained data show that melanin significantly increases the stiffness of pigmented melanoma cells and that the effect depends on the amount of melanin inside the cells. The dramatic impact of melanin on the nanomechanical properties of cells puts into question widely accepted paradigm about all cancer cells being softer than their normal counterparts. Our findings reveal significant limitations of the nanodiagnosis approach for melanoma and contribute to better understanding of cell elasticity.


Guanidination of the lysine residues present in fibrous elastin and in soluble elastin peptides.
We have found that only 20 to 30% of the lysine residues measured after acid hydrolysis of insoluble elastin and alpha-elastin were blocked by prior guanidination of elastin with o-methylisourea. In contrast free lysine was guanidinated almost 100% and a purified, highly crosslinked peptide fraction of low molecular weight, 85%. The non-reactivity of lysine does not seem to be due to steric hindrance in the fibrous protein or in the large peptides derived therefrom but rather to the presence of epsilon [delta-adipic acid]-lysine, the oxidized form of lysinonorleucine described by Bailey et al. Since photolysis of desmosine and isodesmosine leads also to the formation of new lysine residues, methods will have to be devised to distinguish lysine-containing peptides derived from photolyzed elastin.


Baicalein Alleviates Osteoarthritis Progression in Mice by Protecting Subchondral Bone and Suppressing Chondrocyte Apoptosis Based on Network Pharmacology.
As life expectancy increases, Osteoarthritis (OA) is becoming a more frequently seen chronic joint disease. The main characteristics of OA are loss of articular cartilage, subchondral bone sclerosis, and synovial inflammation. Baicalein (Bai), a traditional Chinese medicine extracted from Scutellaria baicalensis Georgi, has been demonstrated to exert notable anti-inflammatory effects in previous studies, suggesting its potential effect in the treatment of OA. In this study, we first predicted the action targets of Bai, mapped target genes related to OA, identified potential anti-OA targets for Bai, performed gene ontology (GO) enrichment, and KEGG signaling pathway analyses of the action targets, and analyzed the molecular docking of key Bai targets. Additionally, the effect and potential mechanism of Bai against OA were verified in mouse knee OA models induced by destabilized medial meniscus (DMM) surgery. GO and KEGG analyses showed that 19 anti-OA targets were mainly involved in the response to oxidative stress, the response to hypoxia and apoptosis, and the PI3K-Akt and p53 signaling pathways. Molecular docking results indicated that BAX, BCL 2, and Caspase 3 enriched in the apoptotic signaling pathway have high binding affinity with Bai. Validation experiments showed that Bai can significantly attenuate the loss of articular cartilage (OARSI score), suppress synovial inflammation (synovitis score), and ameliorate subchondral bone resorption measured by micro-CT. In addition, Bai notably inhibited the expression of apoptosis-related proteins in articular cartilage (BAX, BCL 2, and Caspase 3). By combining network pharmacology with experimental validation, our study identifies and verifies the importance of the apoptotic signaling pathway in the treatment of OA by Bai. Bai may have promising application and potential therapeutic value in OA treatment.


Removal of a Giant Cyst of the Left Ovary from a Pregnant Woman in the First Trimester by Laparoscopic Surgery under Spinal Anesthesia during the COVID-19 Pandemic.
This paper reports a case of a 21 year old primigravida at 6 weeks gestation, suffering from important abdominal pain, who was admitted into the medical center with a giant cyst of 28 × 20 cm on her left ovary. A torsion of the ovarian cyst was suspected. Her COVID-19 status was unknown. In view of the emergency of the situation and the COVID-19 pandemic, laparoscopy in spinal anesthesia was performed. The patient remained conscious during the surgical intervention and tolerated it well apart from a slight dyspnea, which was easily eliminated by changing her body position and decreasing the pneumoperitoneum pressure. The ovarian cyst was removed by enlarging the trocar incision. The patient recovered with neither incident nor pregnancy loss. COVID-19-related complications can induce adverse pregnancy outcomes. Under general anesthesia, patients with COVID-19 are at risk of severe pneumonia and of passing their infection to the medical personnel. To avoid such complications in non-specialized centers, laparoscopy should be performed in regional anesthesia. Laparoscopy in spinal anesthesia can be performed safely on pregnant patients by placing them in the proper position, using a low pneumoperitoneum, and monitoring the hemodynamics. During early pregnancy, general anesthesia induces a higher risk of teratogenic effects and of miscarriage.


Impact of diet in shaping gut microbiota revealed by a comparative study in infants during the six months of life.
The development of the gut is controlled and modulated by different interacting mechanisms, such as genetic endowment, intrinsic biological regulatory functions, environment influences and last but no least, the diet influence. In this work, we compared the fecal microbiota of breast-fed (BF), formula-fed (FF), and mixed-fed (MF) infants from Hebei Province, China. By using high-throughput 16S rDNA sequencing analyses, we found some differences in gut microbiota in the three groups. Firmicutes and Proteobacteria were the dominant bacteria at the phylum level in the three groups, where FF infants showed a significant depletion in Bacteroidetes (p < 0.001) and Actinobacteria (p < 0.05). Enterobacteriaceae was the dominant bacteria at the family level in the three groups, but FF infants showed higher Enterobacteriaceae enrichment than BF and MF infants (p < 0.05); the abundance of the Bifidobacteriaceae was only 8.16% in the feces of BF infants, but higher than in MF and FF infants (p < 0.05). The number of genera detected (abundance >0.01%) in BF, MF, and FF infants was only 15, 16, and 13, respectively. This study could provide more accurate and scientific data for the future study of infant intestinal flora.


Evolving Orthogonal Suppressor tRNAs To Incorporate Modified Amino Acids.
There have been considerable advancements in the incorporation of noncanonical amino acids (ncAA) into proteins over the last two decades. The most widely used method for site-specific incorporation of noncanonical amino acids, amber stop codon suppression, typically employs an orthogonal translation system (OTS) consisting of a heterologous aminoacyl-tRNA synthetase:tRNA pair that can potentially expand an organism's genetic code. However, the orthogonal machinery sometimes imposes fitness costs on an organism, in part due to mischarging and a lack of specificity. Using compartmentalized partnered replication (CPR) and a newly developed pheS negative selection, we evolved several new orthogonal Methanocaldococcus jannaschii (Mj) tRNA variants tRNAs with increased amber suppression activity, but that also showed up to 3-fold reduction in promiscuous aminoacylation by endogenous aminoacyl-tRNA synthetases (aaRSs). The increased orthogonality of these variants greatly reduced organismal fitness costs associated in part due to tRNA mischarging. Using these methods, we were also able to evolve tRNAs that supported the specific incorporation of 3-halo-tyrosines (3-Cl-Y, 3-Br-Y, and 3-I-Y) in E. coli.


Neurochemical characterization of the tree shrew dorsal striatum.
The striatum is a major component of the basal ganglia and is associated with motor and cognitive functions. Striatal pathologies have been linked to several disorders, including Huntington's, Tourette's syndrome, obsessive-compulsive disorders, and schizophrenia. For the study of these striatal pathologies different animal models have been used, including rodents and non-human primates. Rodents lack on morphological complexity (for example, the lack of well defined caudate and putamen nuclei), which makes it difficult to translate data to the human paradigm. Primates, and especially higher primates, are the closest model to humans, but there are ever-increasing restrictions to the use of these animals for research. In our search for a non-primate animal model with a striatum that anatomically (and perhaps functionally) can resemble that of humans, we turned our attention to the tree shrew. Evolutionary genetic studies have provided strong data supporting that the tree shrews (Scadentia) are one of the closest groups to primates, although their brain anatomy has only been studied in detail for specific brain areas. Morphologically, the tree shrew striatum resembles the primate striatum with the presence of an internal capsule separating the caudate and putamen, but little is known about its neurochemical composition. Here we analyzed the expression of calcium-binding proteins, the presence and distribution of the striosome and matrix compartments (by the use of calbindin, tyrosine hydroxylase, and acetylcholinesterase immunohistochemistry), and the GABAergic system by immunohistochemistry against glutamic acid decarboxylase and Golgi impregnation. In summary, our results show that when compared to primates, the tree shrew dorsal striatum presents striking similarities in the distribution of most of the markers studied, while presenting some marked divergences when compared to the rodent striatum.


Two multiplex assays that simultaneously identify 22 possible mutation sites in the KRAS, BRAF, NRAS and PIK3CA genes.
Recently a number of randomized trials have shown that patients with advanced colorectal cancer do not benefit from therapies targeting the epidermal growth factor receptor when their tumors harbor mutations in the KRAS, BRAF and PIK3CA genes. We developed two multiplex assays that simultaneously screen 22 nucleotides in the KRAS, NRAS, BRAF and PIK3CA genes for mutations. The assays were validated on 294 tumor DNA samples from patients with advanced colorectal cancer. In these samples 119 KRAS codon 12 and 13 mutations had been identified by sequence analysis, 126 tumors were wild-type for KRAS and the analysis failed in 49 of the 294 samples due to poor DNA quality. The two mutation assays detected 130 KRAS mutations, among which were 3 codon 61 mutations, and in addition 32 PIK3CA, 13 BRAF and 6 NRAS mutations. In 19 tumors a KRAS mutation was found together with a mutation in the PIK3CA gene. One tumor was mutant for both PIK3CA and BRAF. In summary, the mutations assays identified 161 tumors with a mutation, 120 were wild-type and the analysis failed in 13. The material cost of the 2 mutation assays was calculated to be 8-fold lower than the cost of sequencing required to obtain the same data. In addition, the mutation assays are less labor intensive. We conclude that the performance of the two multiplex mutation assays was superior to direct sequencing. In addition, these assays are cheaper and easier to interpret. The assays may also be of use for selection of patients with other tumor types.


Environmental structure and competitive scoring advantages in team competitions.
In most professional sports, playing field structure is kept neutral so that scoring imbalances may be attributed to differences in team skill. It thus remains unknown what impact environmental heterogeneities can have on scoring dynamics or competitive advantages. Applying a novel generative model of scoring dynamics to roughly 10 million team competitions drawn from an online game, we quantify the relationship between the structure within a competition and its scoring dynamics, while controlling the impact of chance. Despite wide structural variations, we observe a common three-phase pattern in the tempo of events. Tempo and balance are highly predictable from a competition's structural features alone and teams exploit environmental heterogeneities for sustained competitive advantage. Surprisingly, the most balanced competitions are associated with specific environmental heterogeneities, not from equally skilled teams. These results shed new light on the design principles of balanced competition, and illustrate the potential of online game data for investigating social dynamics and competition.


Dose-response and self-efficacy effects of an exercise program on vigor change in obese women.
The causative factors of exercise-induced mood change remain unclear. The objective of this study was to clarify the relationship of exercise with change in vigor (energy level). Obese women in an exercise support treatment (n = 122) or control condition (n = 70) were assessed on vigor, exercise barriers self-efficacy, and physical self-concept at baseline and at month 6. Exercise session attendance was also assessed in the treatment group. The relationship between exercise attendance and vigor change was tested. Multiple regression analyses also tested whether change in vigor was predicted by exercise barriers self-efficacy and physical self-concept scores, both at baseline and change over 6 months. Vigor, exercise barriers self-efficacy, and physical self-concept were significantly improved in the treatment group only. Exercise session attendance was not significantly related to change in vigor. Multiple regression analyses indicated that exercise barriers self-efficacy and physical self-concept scores, both at baseline and change from baseline to month 6, explained a significant portion of the variance in changes in vigor (Radj = 0.13 and 0.21, respectively). In post hoc analyses, entry of depressed mood (indicated by a cut point on depression score) into the regression equations increased the variance accounted for to Radj = 0.15 and 0.25, respectively. Findings supported behavioral explanations of the exercise-mood change relationship emanating from social cognitive and self-efficacy theory. The use of manageable amounts of exercise early in the weight loss intervention process was suggested.


Stability of Rosmarinic Acid and Flavonoid Glycosides in Liquid Forms of Herbal Medicinal Products-A Preliminary Study.
Peppermint leaf, sage leaf, thyme herb, and their preparations are common components of herbal medicinal products (HMPs). According to the European Pharmacopoeia guidelines, the above-mentioned plant substances are standardized for the content of essential oils, omitting polyphenols, which also have a significant impact on their activities. The aim of this study was to evaluate the stability of the predominant polyphenols-rosmarinic acid, luteolin-7-O-β-glucuronide, and eriocitrin-in selected commercial liquid HMPs containing thyme, sage, and peppermint under long-term, intermediate, and accelerated testing conditions. Qualitative and quantitative analyses of these polyphenols were performed by the previously optimized and validated HPLC-DAD method. Rosmarinic acid stability was better in hydroethanolic than in an aqueous solution. The effect of the solvent on the stability of luteolin-7-O-β-glucuronide and eriocitrin could not be determined and requires further investigation. The present study is the first to analyze the stability of these compounds in commercial herbal medicinal products. The expiration dates proposed by the manufacturers of the tested HMPs did not guarantee stable levels of all analyzed polyphenols throughout the stated period. However, this study is preliminary and requires continuation on a larger number of medicinal products.


Psychometric Properties of the BIS/BAS Scales and the SPSRQ in Flemish Adolescents.
Gray's Reinforcement Sensitivity Theory (RST) is a frequently used model of personality that is relevant to the period of adolescence. However, the psychometric properties of the most frequently used questionnaires to measure the RST-constructs, namely the Behavioural Inhibition System and Behavioural Activation System Scales (BIS/BAS Scales) and the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), are rarely examined in samples of adolescents. Therefore, the goal of the present study was to examine the two-factor structure, reliability and convergent validity of the BIS/BAS Scales and SPSRQ in a Flemish adolescent community sample. A sample of 579 adolescents (39.5% boys; 14-19 years) was recruited. The proposed two-factor structure was assessed using Exploratory Structural Equation Modeling. Reliability was evaluated using internal consistency and construct validity was examined with the correlations between the two questionnaires and with the Temperament and Character Inventory-short form (TCI-SF). After the removal of problematic items, and the addition of correlated errors, all indices indicated a good fit for the two-factor structure of the modified BIS/BAS Scales. For the modified SPSRQ, three fit indices indicated a good model fit, while a fourth fit index was slightly below the cut-off score of an adequate model fit. Internal consistency of both questionnaires was sufficient. In general, the associations with scales of the TCI-SF were as expected, with positive correlations between BIS-related scales, and between BAS-related scales of all three instruments. In Flemish adolescents, the use of a two-factor model to analyze data gathered with the modified BIS/BAS Scales or modified SPSRQ seems appropriate.


[125th birth anniversary of the outstanding botanist Peter Mikhailovich Zhukovsky].
Peter Mikhailovich Zhykovsky--botanist, monograph of the genus Aegilops, closest associate of N.N. Vavilov, Director of the All-Union Institute of Plant Industry, Academic Secretary of the Department of Agriculture of VASKhNIL, and the first Editor-in-Chief of the Genetika journal. He postulated a theory on host-parasite coevolution at their common place of origin, and put forward the concept on Megagene centers of origin of cultivated plants and their endemic Microgene centers. He discovered and described the new wheat species Triticum timopheevii (Zhuk.) Zhuk. This species is unique with respect to its immunity to diseases and pests, and is the carrier of the genes for cytoplasmic male sterility.


[Identification and management of intra-operative suspicious tissues in 20 transsphenoidal surgery cases].
To determine appropriate protocols for the identification and management of intra operative suspicious tissues during transsphenoidal surgery. Clinical data and pathological reports of 20 patients with intra-operative suspicious tissues during transsphenoidal surgeries were analyzed retrospectively. The methods for discriminating between adenoma and normal pituitary tissues were reviewed. The postoperative pathological reports revealed that adenoma and normal pituitary tissues coexisted in 9 samples, while 5 samples were identified as normal pituitary tissues, 2 as adenoma tissues, and 4 as other tissues. Adenomas were distinguished from normal pituitary tissues on the basis of intra-operative appearance, texture, blood supply and possible existence of boundary. If decisions are difficult to made during surgeries from the appearance of the suspicious tissues, pathological examinations are advised as a guidance for the next steps.


Influence of nanoporous poly(ether imide) particle extracts on human aortic endothelial cells (HAECs).
Accumulated uremic toxins like indoxyl sulphate, hippuric acid and p-cresyl sulphates in renal failure patients stimulate proinflammatory effects, and consequently kidney and cardiovascular diseases. Low clearance rate of these uremic toxins from the blood of uremic patients by conventional techniques like hemodialysis is due to their strong covalent albumin binding (greater than 95%) and hydrophobic nature, which led to alternatives like usage of hydrophobic adsorber's in removing these toxins from the plasma of kidney patients. Polymers like polyethylene, polyurethane, polymethylmethacrylate, cellophane and polytetrafluoroethylene were already in use as substitutes for metal devices as dialysis membranes. Among new synthetic polymers, one such ideal adsorber material are highly porous microparticles of poly(ether imide) (PEI) with diameters in the range from 50-180μm and a porosity around 88±2% prepared by a spraying and coagulation process.It is essential to make sure that these synthetic polymers should not evoke any inflammatory or apoptotic response during dialysis. Therefore in our study we evaluated in vitro effect of PEI microparticle extracts in human aortic endothelial cells (HEACs) concerning toxicity, inflammation and apoptosis. No cell toxicity was observed when HAECs were treated with PEI extracts and inflammatory/apoptotic markers were not upregulated in presence of PEI extracts. Our results ensure biocompatibility of PEI particles and further hemocompatibility of particles will be tested.


Multimodal analgesic treatment in video-assisted thoracic surgery lobectomy using an intraoperative intercostal catheter.
No golden standard for analgesia in video-assisted thoracic surgery (VATS) lobectomy exists. A simple multimodal approach using an intercostal catheter (ICC) may be of benefit since acute post-operative pain following VATS lobectomy primarily originates from the chest drain area. Prospective observational cohort. Forty-eight consecutive patients received a standardized regimen consisting of paracetamol, non-steroidal anti-inflammatory drug and gabapentin. Further, surgeons performed a single-shot paravertebral block (PVB) at five levels (15 ml of 0.5% bupivacaine) and inserted an ICC at the drain site level for continuous delivery of 6 ml of 0.25% bupivacaine h(-1). Pain scores at rest, mobilization and with the extended arms were followed until discharge or for 4 days. Forty-eight patients, mean age 64 years (CI: 61-68), were included. The mean time for the PVB and ICC placement was 5 min (CI: 4.7-5.9). The mean pain score at rest using a numerical rating scale (NRS, 0-10) was <3 for 1-16 h and decreased from 4.7 to 1.7 (NRS day 1-4, getting out of bed). The ICC was removed with the drain in 48/73/92% on day 1/2/3 after surgery. The median day of discharge was 3 (interquartile range 2-4) with >85% of patients reporting satisfactory or very satisfactory pain treatment all days. Acute pain after VATS lobectomy may be adequately controlled using a multimodal non-opioid regime including PVB and an ICC. The low pain scores and reduced time used inserting the ICC may present an alternative to continuous epidural analgesia or conventional PVB.


Surface forces and protein adsorption on dextran- and polyethylene glycol-modified polydimethylsiloxane.
Dextran and polyethylene glycol (PEG) are often covalently bound to the surface of polydimethylsiloxane (PDMS) for the purpose of modifying its hydrophilicity and biocompatibility. In this work, the effects of the dextran and PEG on the morphology, wetting, and surface charge of the resulting surfaces were quantified and correlated with changes in the amount of fibrinogen and albumin adsorbed from aqueous solution. PDMS films were functionalized in a microwave oxygen plasma to create surface hydroxyl groups that were subsequently aminated by incubation in a (3-aminopropyl)trimethoxysilane (APTES) solution. Oxidized dextran and PEG-aldehyde were linked to the surface amines via reductive amination. This process resulted in low surface coverage of immobilized PEG in the end-on conformation and a more uniform and dense distribution of side-on immobilized dextran. The immobilized dextran reduced the contact angle of the PDMS film from 109° to 80° and neutralized the zeta potential over the pH range from 3 to 11. An atomic force microscope was used to measure the interaction force between the modified PDMS and a model hydrophobic surface (polystyrene latex) and a model hydrophilic surface (silica) in aqueous solution to show that van der Waals and hydrophobic attractive forces are the dominant forces for protein adsorption in this system. The PEG- and dextran-modified PDMS were exposed to BSA and fibrinogen to test their resistance to protein adsorption. The coatings were ineffective at reducing the adsorption of either molecule, and the dextran-modification of the PDMS caused more BSA to adsorb than in the case of the unmodified PDMS.


Graphene-facilitated synthesized vertically aligned hexagonal boron nitride nanowalls and their gas adsorption properties.
The capability of hexagonal boron nitride (h-BN) to adsorb gas atoms may stimulate various promising applications in environment remediation and energy storage, while the interactivity with gas molecules yet remains challenging due to its inherent chemical inertness. In this article, we report a feasible and effective route for the scalable synthesis of vertically aligned h-BN nanowalls assisted by reduced graphene oxide (rGO) without metallic catalysts. The average thickness of the fine h-BN nanowalls is few-atomic layers about 3.7 nm, that grow on the large substrate-like flakes transformed from the pristine rGO. The hierarchical h-BN nanowalls exhibit an enhanced gas adsorption performance, not only through physisorption owing to the synergistic combination of different porous geometries, but also through chemisorption via the open edge groups. Moreover, it demonstrates a significantly enhanced adsorption of CO2 over CH4 as compared to the h-BN nanosheets with similar sizes. Density functional theory calculations reveal that the -OH edge groups can effectively increase the adsorption capability towards CO2, accompanied by a shortened adsorption distance when the gas molecule is energetically stabilized. The wetting characteristics of h-BN nanowalls was further examined by contact angle goniometry.


A potential catalytic site revealed by the 1.7-A crystal structure of the amino-terminal signalling domain of Sonic hedgehog.
Within the past few years, members of the hedgehog (hh) family of secreted signalling proteins have emerged as the primary signals generated by certain embryonic patterning centres. In vertebrate embryos, for example, sonic hedgehog expression in the notochord appears to be responsible for the local and long-range induction of ventral cell types within the neural tube and somites (reviewed in refs 1, 2). Protein products encoded by hh family members are synthesized as precursors that undergo autoprocessing to generate an amino-terminal domain that appears to be responsible for both local and long-range signalling activities, and a carboxy-terminal domain that contains the autoprocessing activity. As part of an effort to understand how hh family members participate in cell-to-cell signalling, we have determined and report here the crystal structure at 1.7 A of the amino-terminal domain of murine Sonic hedgehog (Shh-N). The structure revealed a tetrahedrally coordinated zinc ion that appears to be structurally analogous to the zinc coordination sites of zinc hydrolases, such as thermolysin and carboxypeptidase A. This previously unsuspected catalytic site represents a distinct activity from the autoprocessing activity that resides in the carboxy-terminal domain.


A multicentre phase II clinical experience with the novel aza-epothilone Ixabepilone (BMS247550) in patients with relapsed or refractory indolent non-Hodgkin lymphoma and mantle cell lymphoma.
The epothilones represent a novel group of microtubule stabilization agents that appear to retain activity even in chemotherapy-resistant cell lines and animal models. Because of their ability to overcome chemotherapy resistance, we conducted a phase II study of Ixabepilone in patients with indolent non-Hodgkin lymphoma and mantle cell lymphoma (MCL). Ixabepilone was given at a dose of 25 mg/m(2) weekly for three of four consecutive weeks. Patients were required to have received < or =4 prior chemotherapy regimens, with an interval of at least one month since the last treatment, 3 months from prior rituximab, and 7 d from prior steroids, an absolute neutrophil count >1 x 10(9)/l and a platelet count >50 x 10(9)/l. Dose reductions were allowed. The overall response rate in assessable patients was 27% in this otherwise heavily treated population. One patient with chemotherapy-refractory follicular lymphoma attained a complete remission that lasted approximately 8 months. Three responses were also seen in refractory MCL and one in small lymphocytic lymphoma. The duration of response ranged from 2 to 8 months. Major toxicities included fatigue, myelosuppression and neuropathy. These data suggest that Ixabepilone has activity in chemotherapy-refractory lymphoma.


Identification of a "peroxy" intermediate in cytochrome bo3 of Escherichia coli.
The respiratory heme-copper oxidases catalyze the reduction of dioxygen to water and link this chemistry to proton translocation. The main subgroups of the enzyme family are the cytochrome c oxidases and the quinol oxidases. For the cytochrome c oxidases, several key intermediates have been described in the oxygen reaction. Two of these (suggested to be "peroxy" and "ferryl" species) are also produced in the reaction of the oxidized enzyme with hydrogen peroxide. However, only a single product (a "ferryl" species) has been reported for the reaction of hydrogen peroxide with the quinol oxidase cytochrome bo3 from Escherichia coli. The same "ferryl" species has also been reported to be produced when two-electron reduced cytochrome bo3 reacts with oxygen, whereas this reaction leads to the "peroxy" intermediate in the cytochrome c oxidases. Consequently, the oxygen reaction has been considered to be different in the two enzyme subgroups. Here we show that both the peroxide reaction and the reaction of the two-electron reduced enzyme with oxygen actually result in primary formation of a hitherto unreported "peroxy" species in cytochrome bo3. This intermediate subsequently relaxes into the "ferryl" species which has been described previously. We conclude that the oxygen reaction is similar in the cytochrome c and quinol oxidases.


Mechanical buckling of veins under internal pressure.
Venous tortuosity is associated with multiple disease states and is often thought to be a consequence of venous hypertension and chronic venous disease. However, the underlying mechanisms of vein tortuosity are unclear. We hypothesized that increased pressure causes vein buckling that leads to a tortuous appearance. The specific aim of this study was to determine the critical buckling pressure of veins. We determined the buckling pressure of porcine jugular veins and measured the mechanical properties of these veins. Our results showed that the veins buckle when the transmural pressure exceeds a critical pressure that is strongly related to the axial stretch ratio in the veins. The critical pressures of the eight veins tested were 14.2 +/- 5.4 and 26.4 +/- 9.0 mmHg at axial stretch ratio 1.5 and 1.7, respectively. In conclusion, veins buckle into a tortuous shape at high lumen pressures or reduced axial stretch ratios. Our results are useful in understanding the development of venous tortuosity associated with varicose veins, venous valvular insufficiency, diabetic retinopathy, and vein grafts.


Individual responses in biomarkers of health after marathon and half-marathon running: is age a factor in troponin changes?
Although strenuous physical activity is known to cause notable perturbations in blood chemistries, only few studies exist observing exercise-induced simultaneous changes in biomarkers of health status. We compared markers of muscle, cardiovascular, renal, hepatic and inflammatory status at baseline and at 3-h and at 48-h postrace in recreational runners who successfully completed either a marathon (mean age 27 ± 13 years, finishing time 199 ± 8 min, n = 4) or half-marathon (mean age 38 ± 13 years, finishing time 131 ± 6 min, n = 6) race. Significant postrace changes occurred in myoglobin (p < .001), creatinine kinase (p < .01), CK-MB-mass (p < .01), high sensitivity troponin I (p < .05), high sensitivity troponin T (p < .05), brain natriuretic peptide (p < .001), creatinine (p < .01), aminotransferase enzymes (p < .001 for AST and p < .01 for ALT), uric acid (p < .001) cortisol (p < .01), C-reactive protein (p < .05), leukocytes (p < .001), haematocrit (p < .05) and mean corpuscular volume (p < .01). In comparison between the two types of exercise, marathon running lead to more pronounced responses in myoglobin, CK-MB-mass, ALT, AST, lactate and phosphate. Notable elevations in troponin levels were observed only in young participants (<30 years), most strikingly in those ≤20 years of age. The data indicates that prolonged running leads to distinct biomarker alterations, which should be considered in the assessment of health status after recent acute bouts of strenuous exercise. The observations suggesting more pronounced cardiac troponin responses in young individuals warrant further studies in larger populations.


Changes in food habits in families with a newly diagnosed child with type 1 diabetes mellitus.
Dietary recommendations for children with type 1 diabetes mellitus (DM) are in line with the recommendations for the general population and applicable to the whole family. We review what is known about the food habits of non-diabetic family members and present original data on dietary changes in families with a child with DM. Some studies suggest that family members eat mostly the same food as the affected child. In a Finnish study of siblings of children with DM, favourable changes were observed after diagnosis in the type of milk and fat used. In a study of young children with DM, family members increased their consumption of skim milk, low-fat cheese and low-fat cold meat cuts. The consumption frequencies of fruit and vegetables increased. In conclusion, family members of a child with DM are willing to change their food habits towards the recommended diet. Dietary advice should be directed to the whole family from the very beginning.


Spinal gap junctions: potential involvement in pain facilitation.
Glia are now recognized as important contributors in pathological pain creation and maintenance. Spinal cord glia exhibit extensive gap junctional connectivity, raising the possibility that glia are involved in the contralateral spread of excitation resulting in mirror image pain. In the present experiments, the gap junction decoupler carbenoxolone was administered intrathecally after induction of neuropathic pain in response to sciatic nerve inflammation (sciatic inflammatory neuropathy) or partial nerve injury (chronic constriction injury). In both neuropathic pain models, a low dose of carbenoxolone reversed mirror image mechanical allodynia, while leaving ipsilateral mechanical allodynia unaffected. Ipsilateral thermal hyperalgesia was briefly attenuated. Critically, blockade of mechanical allodynia and thermal hyperalgesia was not observed in response to intrathecal glycyrrhizic acid, a compound similar to carbenoxolone in all respects but it does not decouple gap junctions. Thus, blockade of mechanical allodynia and thermal hyperalgesia by carbenoxolone does appear to reflect an effect on gap junctions. Examination of carbenoxolone's effects on intrathecal human immunodeficiency virus type 1 gp120 showed that blockade of pain facilitation might result, at least in part, via suppression of interleukin-1 and, in turn, interleukin-6. These data provide the first suggestion that spread of excitation via gap junctions might contribute importantly to inflammatory and traumatic neuropathic pain. The current studies provide evidence for involvement of gap junctions in spinal cord pain facilitation. Intrathecal carbenoxolone, a gap junction decoupler, reversed neuropathy-induced mirror image pain and intrathecal gp120-induced allodynia. In addition, it decreased gp120-induced proinflammatory cytokines. This suggests gap junction activation might lead to proinflammatory cytokine release by distantly activated glia.


Improvement of vascular dysfunction and blood lipids of insulin-resistant rats by a marine oil-based phytosterol compound.
The syndrome that is characterized by obesity, insulin resistance, and hyperlipidemia is increasingly prevalent in all prosperous societies. It is now recognized as a major contributor to cardiovascular disease. Vascular dysfunction in the form of hypercontractility and impaired nitric oxide-mediated relaxation is a significant component of cardiovascular disease, predisposing to ischemic events. The JCR:LA-cp strain of rats exhibits all major aspects of the obesity/insulin resistance syndrome, including vascular dysfunction and ischemic lesions of the heart. Dietary lipid intake may have a marked effect on plasma lipid levels and, potentially, on vascular disease. We have investigated the effects of a novel preparation, ONC101 (a phytosterol esterified with fish oil), on plasma lipids and vascular function in the insulin-resistant JCR:LA-cp rat. Treatment of obese male rats with ONC101 from 8 to 12 wk of age resulted in no change in plasma lipid concentrations at 0.5 g/kg body weight. At the higher dose of 2.6 g/kg, plasma TG fell 50% (1.26 vs. 2.59 mmol/L, P < 0.002) and cholesterol esters were significantly reduced (1.34 vs. 1.61 mmol/L, P < 0.002). Food intake and body weights were unaffected by ONC101 treatment. At the low dose of 86 mg/kg, the hypercontractility of aortic rings in response to phenylephrine was normalized and the relaxant response to acetylcholine was significantly improved. The results indicate that ONC101 at high doses has significant hypolipidemic effects and, at very low doses, has beneficial effects on endothelial and vascular smooth muscle cell function.


Sea bass Dicentrarchus labrax (L.) bacterial infection and confinement stress acts on F-type lectin (DlFBL) serum modulation.
The F-lectin, a fucose-binding protein found from invertebrates to ectothermic vertebrates, is the last lectin family to be discovered. Here, we describe effects of two different types of stressors, bacterial infection and confinement stress, on the modulation of European sea bass Dicentrarchus labrax (L.) F-lectin (DlFBL), a well-characterized serum opsonin, using a specific antibody. The infection of the Vibrio alginolyticus bacterial strain increased the total haemagglutinating activity during the 16-day testing period. The DlFBL value showed an upward regulation on the first, second and last days and underwent a slight downward regulation 4 days post-challenge. In contrast, the effect of confinement and density stress showed a decrease in the plasma concentration of lectin, ranging from 50% to 60% compared with the control. The modulation of DlFBL is in line with the hypothesis that humoral lectins could be involved and recruited in the initial recognition step of the inflammation, which leads to agglutination, and the activation of mechanisms responsible for killing of the pathogens.


Quantum-coherent nanoscience.
For the past three decades nanoscience has widely affected many areas in physics, chemistry and engineering, and has led to numerous fundamental discoveries, as well as applications and products. Concurrently, quantum science and technology has developed into a cross-disciplinary research endeavour connecting these same areas and holds burgeoning commercial promise. Although quantum physics dictates the behaviour of nanoscale objects, quantum coherence, which is central to quantum information, communication and sensing, has not played an explicit role in much of nanoscience. This Review describes fundamental principles and practical applications of quantum coherence in nanoscale systems, a research area we call quantum-coherent nanoscience. We structure this Review according to specific degrees of freedom that can be quantum-coherently controlled in a given nanoscale system, such as charge, spin, mechanical motion and photons. We review the current state of the art and focus on outstanding challenges and opportunities unlocked by the merging of nanoscience and coherent quantum operations.


[Selective reduction of NOx with propene over SnO2/Al2O3 catalyst].
In the study, a series of SnO2/Al2O3 catalysts with various Sn loading were prepared by three different methods (impregnation, co-precipitation and single step sol-gel) and their catalytic activities for the selective reduction of NOx with propene were investigated. It was found that the catalyst preparation method as well as the Sn loading exerted a significant influence on the catalyst activity. Catalysts prepared by sol-gel method exhibited the highest activity toward NOx reduction and the optimal Sn loading is 5%. 5% SnO2/Al2O3 catalyst prepared by sol-gel method was found to be less inhibited by the presence of H20 than those prepared by other methods. Even in the co-presence of H2O and SO2, it still showed the highest activity. The increase of oxygen and propene concentration promotes the NOx reduction, respectively.


Projected Medicare Savings Associated With Lowering the Risk of Total Hip Arthroplasty Revision: An Administrative Claims Data Analysis.
In the United States, demand for total hip arthroplasty (THA) and THA revision procedures are increasing due to an aging population, a longer life expectancy, and an increasing prevalence of osteoarthritis. This retrospective cohort study identified patients 65 years and older in the Medicare 5% Standard Analytic Files who underwent THA for osteoarthritis between January 1, 2009, and September 30, 2010. The authors estimated the 5-year cumulative revision risk (CRR) using the Kaplan-Meier method, revision-related complications, and Medicare expenditures. Using a 6.22% compound annual growth rate from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality, the authors estimated the number of THAs that will be performed from 2018 to 2027 and calculated the 10-year projected savings to Medicare for a 1% reduction in CRR. Among 7820 patients, the mean age was 74.4 years, and 62.4% were female. Cumulative revision risk was 4.2% at 5 years (through September 30, 2015), with 30.8% of revisions occurring within 90 days of the THA. At least 24.4% of revision patients had a complication. Median revision inpatient stay and episode of care (through 90 days) expenditures were $23,847 and $36,157, respectively. With a 1% absolute reduction in CRR, Medicare could save $697 million over a 10-year period, or $985 million when including Medicare Advantage, which represented 29.2% of 2016 Medicare payments. Strategies to reduce the risk of THA revision, such as the use of implant constructs with lower CRR and value-based payment models, are needed to achieve Medicare payment reductions while maintaining or improving quality of care for Medicare beneficiaries. [Orthopedics. 2019; 42(1):e86-e92.].


Arabinogalactan-Proteins from Primary and Mature Roots of Radish (Raphanus sativus L.).
Organ-specific variations in blood group H-like activity were observed in developing radish plants. A temporary increase in serological activity was found to occur in the roots at the earlier stages of development. Arabinogalactan-proteins (AGPs) were isolated from primary and mature roots, and investigated for changes in their physicochemical properties, structure, and serological activities. These root AGPs were composed mainly of l-arabinose and d-galactose but were distinguishable from each other in their contents of l-fucose as well as of protein and hydroxyproline. The structures of the carbohydrate moieties of the root AGPs were essentially similar to those of AGPs isolated from seeds and mature leaves in that they consisted of consecutive (1-->3)-linked beta-d-galactosyl backbone chains having side chains of (1-->6)-linked beta-d-galactosyl residues, to which alpha-l-arabinofuranosyl residues were attached in the outer regions. One prominent feature of the primary root AGPs was that they contained appreciable amounts of l-fucose, which was presumably responsible for expression of the serological activity. In their immunological reactions with rabbit anti-radish leaf AGP antibody, the root AGPs were shown to share common antigenic determinant(s) with those of seed and leaf AGPs.


[Mechanisms of therapeutic action of aloe].
Genus Aloe was traditionally applied for the medicinal practice over thousands of years and used for treatment of wide range of medical indication from stomach disorders to cancer. Fresh leaves of aloe contain various groups of chemical compounds such as: glycoproteins, polysaccharides, anthraquinone derivatives, vitamins, minerals, aminoacids and many others, which show multidirectional therapeutic action. These active components are responsible for immunomodulatory, antiinflammatory and antimicrobial effects of aloe Recent data confirmed that aloe possess a unique therapeutic profile and has positive potential for medical application.


HIV seroprevalence among inmates in Togo.
There is no data on HIV seroprevalence among prisoners in Togo. A cross-sectional study was conducted among prisoners in Togo from November 2011 to January 2012. The study population was included by selecting the most densely populated prison in each of the six Togo regions, and by including prisoners (at least18years of age and having been in prison for more than 30days) on a voluntary basis. HIV prevalence was estimated with a 95% confidence interval (CI). One thousand three hundred and fourty-two prisoners were included in the study. Their median age was 28years, (IQR 25-33years) and 39 (2.9%) were women. The median time spent in the prison was 10months, interquartile range [4-24months]. HIV testing was accepted by 96.0%. HIV seroprevalence in prisons was 4.3%, 95 CI% [3.2-5.5%]. Few prisoners (2.9%) reported having had sex in prisons. The only factor associated with HIV infection was gender with an HIV seroprevalence of 14.3% for women compared to 4.0% for men (P=0.003). The prevention and the management of HIV infection should be a priority in Togolese prisons. This requires implementing healthcare facilities in prisons.


Structure-kinetic relationship study of CDK8/CycC specific compounds.
In contrast with the very well explored concept of structure-activity relationship, similar studies are missing for the dependency between binding kinetics and compound structure of a protein ligand complex, the structure-kinetic relationship. Here, we present a structure-kinetic relationship study of the cyclin-dependent kinase 8 (CDK8)/cyclin C (CycC) complex. The scaffold moiety of the compounds is anchored in the kinase deep pocket and extended with diverse functional groups toward the hinge region and the front pocket. These variations can cause the compounds to change from fast to slow binding kinetics, resulting in an improved residence time. The flip of the DFG motif ("DMG" in CDK8) to the inactive DFG-out conformation appears to have relatively little influence on the velocity of binding. Hydrogen bonding with the kinase hinge region contributes to the residence time but has less impact than hydrophobic complementarities within the kinase front pocket.


24-Month Clinical, Immuno-Virological Outcomes, and HIV Status Disclosure in Adolescents Living With Perinatally-Acquired HIV in the IeDEA-COHADO Cohort in Togo and Côte d'Ivoire, 2015-2017.
Background: Adolescents living with perinatally-acquired HIV (APHIV) face challenges including HIV serostatus disclosure. We assessed their 24-month outcomes in relation to the disclosure of their own HIV serostatus. Methods: Nested within the International epidemiologic Database to Evaluate AIDS pediatric West African prospective cohort (IeDEA pWADA), the COHADO cohort included antiretroviral (ART)-treated APHIV aged 10-19 years, enrolled in HIV care before the age of 10 years, in Abidjan (Côte d'Ivoire) and Lomé (Togo) in 2015. We measured the HIV serostatus disclosure at baseline and after 24 months and analyzed its association with a favorable combined 24-month outcome using logistic regression. The 24-month combined clinical immuno-virological outcome was defined as unfavorable when either death, loss to follow-up, progression to WHO-AIDS stage, a decrease of CD4 count >10% compared to baseline, or a detectable viral load (VL > 50 copies/mL) occurred at 24 months. Results: Overall, 209 APHIV were included (51.6% = Abidjan, 54.5% = females). At inclusion, the median CD4 cell count was 521/mm 3 [IQR (281-757)]; 29.6% had a VL measurement, of whom, 3.2% were virologically suppressed. APHIV were younger in Lomé {median age: 12 years [interquartile range (IQR): 11-15]} compared to Abidjan [14 years (IQR: 12-15, p = 0.01)]. Full HIV-disclosure increased from 41.6% at inclusion to 74.1% after 24 months. After 24 months of follow-up, six (2.9%) died, eight (3.8%) were lost to follow-up, and four (1.9%) were transferred out. Overall, 73.7% did not progress to the WHO-AIDS stage, and 62.7% had a CD4 count above (±10%) of the baseline value (48.6% in Abidjan vs. 69.0% in Lomé, p < 0.001). Among the 83.7% with VL measurement, 48.8% were virologically suppressed (Abidjan: 45.4%, Lomé: 52.5%, p <0.01). The 24-month combined outcome was favorable for 45% (29.6% in Abidjan and 61.4% in Lomé, p < 0.01). Adjusted for baseline variables, the 24-month outcome was worse in Lomé in those who had been disclosed for >2 years compared to those who had not been disclosed to [aOR = 0.21, 95% CI (0.05-0.84), p = 0.03]. Conclusions: The frequency of HIV-disclosure improved over time and differed across countries but remained low among West African APHIV. Overall, the 24-month outcomes were poor. Disclosure before the study was a marker of a poor 24-month outcome in Lomé. Context-specific responses are urgently needed to improve adolescent care and reach the UNAIDS 90% target of virological success.


Regionalization of Congenital Heart Surgery in the United States.
The objective of this study is to simulate regionalization of congenital heart surgery (CHS) in the United States and assess the impact of such a system on travel distance and mortality. Patients ≤18 years of age who underwent CHS were identified in 2012 State Inpatient Databases. Operations were stratified by the Risk Adjustment for Congenital Heart Surgery, version 1 (RACHS-1) method, with high risk defined as RACHS-1 levels 4-6. Regionalization was simulated by progressive closure of hospitals, beginning with the lowest volume hospital. Patients were moved to the next closest hospital. Analyses were conducted (1) maintaining original hospital mortality rates and (2) estimating mortality rates based on predicted surgical volumes after absorbing moved patients. One hundred fifty-three hospitals from 36 states performed 1 or more operation (19,064 operations). With regionalization wherein, all hospitals performed >310 operations, 37 hospitals remained, from 12.5% to 17.4% fewer deaths occurred (83-116/666), and median patient travel distance increased from 38.5 to 69.6 miles (P < 0.01). When only high-risk operations were regionalized, 3.9-5.9% fewer deaths occurred (26-39/666), and the overall mortality rate did not change significantly. Regionalization of CHS in the United States to higher volume centers may reduce mortality with minimal increase in patient travel distance. Much of the mortality reduction may be missed if solely high-risk patients are regionalized.


Single-incision laparoscopic left adrenalectomy.
Single-incision laparoscopic surgery (SILS) has gained an interest and popularity in the recent years. Although minimally invasive adrenal surgery replaced the open adrenalectomy, SILS adrenalectomy is a step forward technique that improves the cosmesis, decreases acsess related morbidity, and increases the postoperative recovery. We report our first experience with single-incision transperitoneal left adrenalectomy in a patient with Conns' syndrome. A 46-year-old female patient with a diagnosis of Conns' syndrome underwent single-incision transperitoneal laparoscopic left adrenalectomy. SILS port (Covidien, Norwalk, CT) was used through a 2-cm incision and additional one 5-mm trocar used through one of the holes of SILS port to solve the smoke problem. The operative time was ended in 50 minutes, and no peroperative complication was encountered. The patient was discharged at the second postoperative day. SILS adrenalectomy is a safe procedure for a benign adrenal lesion in experienced hands. Further studies are needed to evaluate the special benefits of this technique.


Link between Food Energy Density and Body Weight Changes in Obese Adults.
Regulating the energy density of food could be used as a novel approach for successful body weight reduction in clinical practice. The aim of this study was to conduct a systemic review of the literature on the relationship between food energy density and body weight changes in obese adults to obtain solid evidence supporting this approach. The search process was based on the selection of publications in the English language listed in public databases. A meta-analysis was performed to combine individual study results. Thirteen experimental and observational studies were identified and included in the final analysis. The analyzed populations consist of 3628 individuals aged 18 to 66 years. The studies varied greatly in terms of study populations, study design and applied dietary approaches. The meta-analysis revealed a significant association between low energy density foods and body weight reduction, i.e., -0.53 kg when low energy density foods were eaten (95% CI: -0.88, -0.19). In conclusions, this study adds evidence which supports the energy density of food as a simple but effective measure to manage weight in the obese with the aim of weight reduction.


Unilateral retinal hemorrhages with subarachnoid hemorrhage in a 5-week-old infant: is this nonaccidental injury?
Retinal hemorrhages are an important sign in the setting of nonaccidental injury (NAI) (abusive head injury) in young infants and form a very important part of the evidence in support of the diagnosis. The diagnosis of NAI has serious social and legal implications. Other causes of retinal hemorrhages in an infant, such as birth trauma, accidental head injury, subarachnoid hemorrhage, other less common disorders of clotting, leukemia, and infections such as endocarditis, need to be considered and ruled out in making a diagnosis of NAI. Descriptive case report. A 5-week-old child presented with rapid onset of symptoms of drowsiness and hypotonia, unilateral retinal hemorrhages, and an intracranial hemorrhage in the posterior fossa. NAI was high on the list of differential diagnosis, which caused considerable anxiety in the parents. The cause of the intracranial hemorrhage only became apparent at repeat neuroimaging several weeks later. The case is presented to point out arteriovenous malformation as a possible cause of retinal hemorrhages in this age group where an early diagnosis of the etiology is often not possible. A diagnosis of NAI, commonly associated with a similar clinical presentation, can have serious social and legal implications.


Integration of minitransposons for expression of the Escherichia coli elt genes at a preferred site in Salmonella typhimurium identifies a novel putative fimbrial locus.
An asd-complementing mini-Tn5 transposon was constructed for random insertion of the Escherichia coli LT enterotoxin genes (elt) into the genome of Deltaasd attenuated strains of Salmonella typhimurium. Transfer of the minitransposon to different S. typhimurium strains resulted in random integration only in strain chi4072, while in strain chi3987, which harbours the virulence plasmid, over 20% of the insertions occurred at the same site. Expression of elt was found to be highest in Salmonella isolates carrying the mini-Tn5 integrated at the preferred site, which was mapped to an uncharacterised region of the virulence plasmid. Sequence analysis of the integration site showed that it lies within an open reading frame with sequence similarity to E. coli leuO and contiguous to a novel fimbrial locus.


Urinary antigen detection for diagnosis of hydatid disease.
Hydatid antigen was demonstrated for the first time in urine of patients with hydatidosis by coagglutination test (Co-A). Urinary antigen was detected in all Co-A positive serum corresponding samples of surgically confirmed hydatid disease. The sensitivity and specificity were 100% in urine compared with the corresponding serum samples. These results clarified that the use of Co-A test for detection of hydatid antigen in urine is an easy, simple, rapid, non-invasive and efficient method for diagnosis of hydatidosis.


Effects of postharvest treatments on fruit quality of sweet pepper at low temperature.
Postharvest storage of sweet pepper fruits (Capsicum annuum L.) at low temperatures could impair their physical and chemical composition. Therefore, maintenance of essential nutrition support or altered gas exchange could preserve fruit quality, minimizing chilling injury. Thus our aim was to determine the response to postharvest application of a low concentration of nitrogen (urea) or antitranspirant (pinolene) during a period of 21 days at 5 °C. The results indicate that storage at 5 °C was effective with respect to maintaining firmness of sweet pepper fruits for 21 days, while application of antitranspirant increased firmness compared with non-sprayed fruits. Additionally, urea maintained color while increasing total phenolics and the activity of catalase and ascorbate peroxidase, lowering lipid peroxidation. Composition of free amino acids was affected to a minor extent. Maintaining quality is of paramount importance in the postharvest period. This study shows the effect of both temperature and spraying treatments with regard to maintaining fruit quality during this period, and provides new insights into the physiological role of enzymes of the antioxidant system during pepper storage at low temperature.


Reading Level and Comprehension of Research Consent Forms: An Integrative Review.
Consent forms continue to be at a higher reading level than the recommended sixth to eighth grade, making it difficult for participants to comprehend information before enrolling in research. To assess and address the extent of the problem regarding the level of literacy of consent forms and update previously published reports, we conducted an integrative literature review of English language research published between January 1, 2000, and December 31, 2013; 35 descriptive and eight intervention studies met inclusion criteria. Results confirmed that developing forms at eighth-grade level was attainable though not practiced. It was found that risks of participation was the section most poorly understood. There was also a lack of consensus regarding the most effective method to increase comprehension. Further research using standardized tools is needed to determine the best approach for improving consent forms and processes.


Microsatellite DNA: a tool for population genetic analysis.
Microsatellite deoxyribonucleic acid repeats provide a source of high variability that makes them ideal for use in studies requiring such molecular markers, including large population studies and genetic typing of individuals for kinship investigations. This paper provides reviews of the use of such markers in parasitology. Most studies to date have been carried out using protozoan and vector species. Recent investigations have, however, demonstrated their usefulness in the study of helminths, illustrating their ability to distinguish between individuals within hosts as well as from different hosts. The detection of microsatellites within parasites has provided a tool that will prove invaluable in parasitology and should lead to significant advances in our understanding of the processes that affect the organisms' population genetic structure.


On the meaning of "drug seeking".
The term "drug seeking" is frequently used but poorly defined. By soliciting nurses' comments and suggestions, a survey was developed to identify behaviors that may cause nurses to refer to a patient as drug seeking, to identify what nurses think the term "drug seeking" means, to explore how nurses regard the use of the term "drug seeking" in health care, and to identify differences between general nurses, emergency nurses, and pain management nurses with regard to these items. Behaviors that would cause the majority of all three nurse groups to refer to a patient as drug seeking were as follows: going to different emergency departments to get opioids, telling inconsistent stories about pain or medical history, or asking for a refill because the prescription was lost or stolen. When the term "drug seeking" is used, all three groups of nurses agreed that it was very likely to mean the patient was addicted to opioids, the patient was abusing pain medicine, or the patient was manipulative. One-half or more for each nurse group said they used the term "drug seeking" in talking about patients, but less than 10% said they used it in charting. After completing the survey, approximately one half or more of nurses in each group were less inclined to use the term. The use of stigmatizing terms in clinical practice is addressed with suggestions for alternative approaches to patient behavior related to requesting opioids for pain relief.


Iodine-Promoted Construction of Polysubstituted 2,3-Dihydropyrroles from Chalcones and β-Enamine Ketones (Esters).
A novel approach for the synthesis of a variety of polysubstituted trans-2,3-dihydropyrroles from a wide range of chalcones and β-enamine ketones (esters) via iodine-promoted tandem Michael/cyclization sequence has been developed, affording the desired products in moderate to excellent yields. This methodology is a highly efficient, convenient way to access functionalized 2,3-dihydropyrroles from readily accessible substrates under mild reaction conditions.


Apoptosis of endometrial cells in the bitch.
The relationship between apoptosis of endometrial cells in the bitch, and the occurrence of degeneration of the endometrial luminal epithelium and regression of the endometrial glandular epithelium was determined. Mature bitches (n = 12) were ovariectomized and treated with hormones to simulate uterine changes that occur during the oestrous cycle. All bitches were treated with oestradiol benzoate (0.6-4.8 microg x kg(-1), i. m., twice per day) for 11-12 days then with progestagen (megestrol acetate, 2 mg x kg(-1), p. o., once per day) for 35-37 days. Bitches were treated daily for a further 3 weeks with megestrol acetate at dose rates of 0.5 mg x kg(-1) (decreased-dose group (n = 3)), 2 mg x kg(-1) (standard-dose group (n = 3)), or 3 (1 wk), 4 (1 wk) and 5 (1 wk) mg x kg(-1) (increased-dose group (n = 3)), or received no treatment (withdrawal-dose group (n = 3)). These bitches were necropsied at the end of the treatment period. A further 10, ovary-intact, bitches were necropsied when in oestrus (n = 1), dioestrus (n = 5), and at 3 weeks (n = 1) and 9 weeks (n = 3) of anoestrus. Degeneration of the luminal epithelium was observed in all bitches except those in oestrus, at 9 weeks of anoestrus and one in dioestrus. Apoptosis was observed in the glandular epithelial cells, stromal cells and endothelial cells of blood capillaries in all bitches except those at oestrous and at 9 weeks of anoestrous. High average apoptotic indices were detected in the basal glandular epithelium of the dioestrous, decreased-dose, standard-dose and increased-dose groups, whereas low apoptotic indices were detected at 3 weeks of anoestrous and in the withdrawal-dose groups. These results indicate that degeneration of cells of the glandular epithelium, but not of the luminal epithelium, was due to apoptosis of these cells.


The interview with the donor's family before postmortem cornea procurement.
Asking the family of a deceased patient to consider eye donation is one of the most difficult aspects of the donation process. The aim of this prospective study was to describe the content of interviews with the families of potential donors and to analyze their reactions to improve the process of eye donation. We consecutively met with 151 families of suitable corneal donors at the Rouen University Hospital. All interviews with donor families were analyzed using a preestablished questionnaire. In only 17.9% of cases was the family aware of the potential donor's last will. In 77.7% of these cases, the patient wished to donate. Procurement rate was 71.5%. This acceptance was mostly facilitated by the awareness and motivation of the hospital staff, the experience of the physician, and the 13.3-h period of time allowed after the donor's death. The commitment on the part of the ophthalmologist to carry out optimal anatomical restoration was a very important point for 32% of families who accepted donation. Twenty-one percent of families asked for a delay for reflection. This delay helped to obtain a positive response in 72.7% of cases and even sometimes helped families to reconsider a previously negative position (14% of initial refusals). We demonstrate that a high positive response (71.5%) can be obtained from the donor's family when a trained and motivated group manages the post-mortem cornea donation request.


Susceptibility of different developmental stages of Trichogramma parasitoids to insecticides commonly used in the Mediterranean olive agroecosystem.
Insecticide application and augmentative parasitoid releases are often considered incompatible. However, pesticide applications and parasitoid releases can be integrated into a pest management scheme if there is careful time scheduling of these interventions. In this study, we assessed the influence of commonly used insecticides (chlorpyrifos-methyl, deltamethrin, pyriproxyfen, thiamethoxam) in olive agroecosystems to two currently present Trichogramma parasitoids in the Mediterranean basin. Exposure to insecticides in relation to parasitoid's development was also tested. Both, insecticide type and application time influenced parasitism and the emergence rates of the two parasitoid species. Chlorpyrifos-methyl had the strongest impact on parasitoids resulting in low numbers of emerged adults followed by deltamethrin. The two parasitoids also exhibited different levels of susceptibility to the insecticides used. Potential integration of insecticides to integrated pest management using Trichogramma parasitoids is discussed.


Initial color change and color retention with a hydrogen peroxide bleaching strip.
A randomized, double blind clinical trial was conducted to evaluate initial color improvement and post-treatment color retention following vital bleaching with a strip-based tooth whitening system. After balancing for baseline color, 57 healthy adults were randomized to either whitening strips with a 5.3% hydrogen peroxide bleaching gel (Crest Whitestrips) or placebo strips without hydrogen peroxide. Maxillary and mandibular anterior teeth were treated twice daily for 30 minutes each over a 2-week period, and efficacy was measured objectively by comparing digital images of teeth collected at baseline, end-of-treatment (Week 2) and 6 months after treatment (Month 6). The whitening strip group experienced a highly significant (P< 0.0001) reduction in yellow of -2.0 deltab* units versus baseline and -1.95 deltab* units versus placebo, with similar results noted for the other color parameters in the study. Most of the initial color change remained at 6 months post-treatment, with the whitening strip group continuing to demonstrate highly significant (P< 0.0001) improvements in tooth color relative to baseline and placebo. Age was found to significantly contribute to initial color improvement, with younger subjects experiencing a greater initial reduction in yellowness compared to older participants, but not to post-treatment color retention. The whitening strips were well tolerated, with minor tooth sensitivity and oral irritation representing the most common findings during treatment. There were no persistent or new treatment-related adverse events during the 6-month monitoring period.


[Flow imaging of residual neck lymph nodes in nasopharyngeal carcinoma by contrast-enhanced ultrasonography after radiotherapy].
To explore the value of flow imaging with contrast-enhanced ultrasound for residual neck lymph nodes in nasopharyngeal carcinoma after radiotherapy. Blood flow imaging of 50 residual cervical lymph nodes in 36 patients with nasopharyngeal carcinoma after radiotherapy was observed and compared by color doppler ultrasound and contrast-enhanced ultrasonography. In the 50 remaining lymph nodes in the neck, 40 blood flow signals were increased, 10 did not significant change by contrast-enhanced ultrasonography. The blood flow in residual lymph nodes by contrast-enhanced ultrasonography was richer than that by color doppler ultrasound. There was a significant difference in the blood flow signals between contrast-enhanced ultrasonography and color doppler ultrasound (chi(2)=49.172, P<0.01). Contrast-enhanced ultrasonography can help blood flow imaging of the residual lymph nodes in nasopharyngeal carcinoma after radiotherapy, which may provide the imaging basis for clinical diagnosis and treatment.