Structure and biological activity of novel FN analogs as flowering inducers.
(12Z,15Z)-9-Hydroxy-10-oxooctadeca-12,15-dienoic acid (1) and norepinephrine (2) undergo cycloaddition to afford FN1 (3) and FN2 (4), both of which induce flowering in Lemna paucicostata. Although the derivatives of 1 were suggested to also yield FN-like compounds after reacting with 2, their structures have not been elucidated. In this report, we investigated the structure and stereochemistry of seven novel FN analogs. These analogs were shown to be formed in the same regio- and stereocontrolled manner as FNs. Moreover, the activity of FN analogs on flowering induction was investigated, and we determined that all analogs, except for compound 8, were effective flowering inducers for L. paucicostata.


A Genome-Wide Association Study for Susceptibility to Axial Length in Highly Myopic Eyes.
High myopia has long been highly prevalent worldwide with a largely yet unexplained genetic contribution. To identify novel susceptibility genes for axial length (AL) in highly myopic eyes, a genome-wide association study (GWAS) was performed using the genomic dataset of 350 deep whole-genome sequencing data from highly myopic patients. Top single nucleotide polymorphisms (SNPs) were functionally annotated. Immunofluorescence staining, quantitative polymerase chain reaction, and western blot were performed using neural retina of form-deprived myopic mice. Enrichment analyses were further performed. We identified the four top SNPs and found that ADAM Metallopeptidase With Thrombospondin Type 1 Motif 16 (ADAMTS16) and Phosphatidylinositol Glycan Anchor Biosynthesis Class Z (PIGZ) had the potential of clinical significance. Animal experiments confirmed that PIGZ expression could be observed and showed higher expression level in form-deprived mice, especially in the ganglion cell layer. The messenger RNA (mRNA) levels of both ADAMTS16 and PIGZ were significantly higher in the neural retina of form-deprived eyes (p = 0.005 and 0.007 respectively), and both proteins showed significantly upregulated expression in the neural retina of deprived eyes (p = 0.004 and 0.042, respectively). Enrichment analysis revealed a significant role of cellular adhesion and signal transduction in AL, and also several AL-related pathways including circadian entrainment and inflammatory mediator regulation of transient receptor potential channels were proposed. In conclusion, the current study identified four novel SNPs associated with AL in highly myopic eyes and confirmed that the expression of ADAMTS16 and PIGZ was significantly upregulated in neural retina of deprived eyes. Enrichment analyses provided novel insight into the etiology of high myopia and opened avenues for future research interest. The online version contains supplementary material available at 10.1007/s43657-022-00082-x.


Sleep deprivation alleviates depression-like behaviors in mice via inhibiting immune and inflammatory pathways and improving neuroplasticity.
Sleep deprivation (SD) has been suggested to have a rapid antidepressant effect. There is substantial evidence that neuroinflammation and neuroplasticity play critical roles in the pathophysiology and treatment of depression. Here, we investigated the mechanisms of SD to alleviate depression-like behaviors of mice, and the role of neuroinflammation and neuroplasticity in it. Adult male C57BL/6 J mice were subjected to chronic restraint stress (CRS) for 6 weeks, and 6 h of SD were administrated. Behavioral tests were performed to measure depression-like behaviors. RNA-sequencing and bioinformatic analysis were performed in the anterior cingulate cortex (ACC). The differentially expressed genes were confirmed by quantitative real-time polymerase chain reaction (RT-qPCR). Neuroinflammation and neuroplasticity were measured by western blotting and immunofluorescence staining. Behavioral tests demonstrated that SD swiftly attenuated the depression-like behaviors induced by CRS. RNA-sequencing identified the upregulated immune and inflammatory pathways after CRS exposure were downregulated by SD. Furthermore, SD reversed the levels of immune and inflammation-related mRNA, pro-inflammatory factors and microglia activation in ACC. Additionally, the impaired neuroplasticity elicited by CRS in the prefrontal cortex (PFC) and ACC were improved by SD. More in-depth studies are required to determine the role of different SD protocols in depressive symptoms and their underlying mechanisms. Our study revealed the rapid antidepressant effect of SD on CRS mice through the reduction of the neuroinflammatory response in ACC and the improvement of neuroplasticity in PFC and ACC, providing a theoretical basis for the clinical application of SD as a rapid antidepressant treatment.


Peer learning partnership: an innovative strategy to enhance skill acquisition in nursing students.
The development of clinical skills for nursing students is a critical component of any undergraduate nursing program. Providing sufficient quality experience for students to develop competence has been recognised as a problem in skill acquisition. At the same time, peer learning has been identified as a valuable strategy for teaching and learning. Nurse academics at a Sydney university recognized these facts and implemented a peer learning strategy into existing first and third year nursing therapeutics units of study. This innovative approach linked the Australian Nursing Council Inc (ANCI) standards of practice to skills acquisition, resulting in third year students increasing their understanding of the relevance of these competency standards to practice. The peer learning strategy involved partnering first and third year students for clinical skills practice sessions. Evaluation of the peer learning approach indicated students valued the experience.


Prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) inherited from her mosaic sSMC(15) mother and a literature review.
We characterized a maternally inherited small supernumerary marker chromosome (sSMC) derived from chromosome 15 according to prenatal detection and made a review on the prenatal sSMC(15) cases with mosaic maternal inheritance. A 29-year-old woman underwent amniocentesis at 19 weeks of gestation due to the high risk of Down syndrome in maternal serum screening. No abnormalities were observed in prenatal ultrasound findings. G-banding analysis revealed a karyotype of 47,XX,+mar. Subsequently, we recalled the couple back for chromosomal analysis. The father's karyotype was normal while the mother's karyotype was 47,XX,+mar[15]/46,XX[35]. Molecular genetic analysis was utilized to identify the marker chromosome. The chromosomal microarray analysis (CMA) results of the mother showed there existed microduplications in the locus of 14q32.33, 15q21.1, 19p12 and Xq26.2, respectively. Then Fluorescence in situ hybridization (FISH) using specific probes for chromosomes 13/21, 14/22, and 15 was applied on the mother and the fetus. And the marker chromosomes for the mother and the fetus were all finally identified as inv dup(15) (D15Z1++, SNRPN-, PML-), which illustrated that the fetus inherited the sSMC(15) from her mother. Finally, a healthy female infant was delivered with no phenotypic abnormalities at 39 weeks. The combined utilization of the molecular genetic technologies, such as FISH and CMA, plays a critical role in the identification of the origins and genetic constitutions of sSMC, which would make a significant contribution to genetic counseling and prenatal diagnosis.


Characterization of MDR and XDR Streptococcus pneumoniae in Canada, 2007-13.
The goal of this study was to characterize Streptococcus pneumoniae demonstrating MDR (resistant to three or more antimicrobial classes) or XDR (resistant to five or more classes) phenotypes, collected from Canada during the CANWARD 2007-13 study. From 2007 to 2013 inclusive, S. pneumoniae isolates were collected as a part of the CANWARD surveillance study. MDR and XDR isolates were subjected to PFGE, MLST, molecular detection of pneumococcal pili and macrolide resistance determinants mef(A/E) and erm(B), sequencing of PBPs 1A, 2B and 2X and comparison with Pneumococcal Molecular Epidemiology Network (PMEN) clones. Of 2129 S. pneumoniae isolates collected during the CANWARD 2007-13 study, 61 (2.9%) were found to be MDR. Of these MDR isolates, 43 (70.5%) were XDR. The most common serotypes for both MDR and XDR S. pneumoniae were 19A and 19F. Twenty-nine of 61 isolates (48%) demonstrated resistance to clarithromycin, clindamycin, doxycycline, penicillin and trimethoprim/sulfamethoxazole. All isolates possessed at least one macrolide resistance determinant and mutations in PBPs 1A, 2B and 2X. The most common clone was piliated, XDR ST320, an internationally circulating double-locus variant of Taiwan(19F)-14 (ST236). Though the rate of MDR S. pneumoniae has remained relatively stable since 2007, XDR strains have emerged in Canada. These strains are virulent, possess resistance determinants and are related to international clones.


Anesthetic activity of the essential oil of Aloysia triphylla and effectiveness in reducing stress during transport of albino and gray strains of silver catfish, Rhamdia quelen.
This study investigated the efficacy of the essential oil (EO) of Aloysia triphylla as an anesthetic for albino and gray strains of silver catfish, Rhamdia quelen. Juveniles were exposed to concentrations between 20 and 800 μL L(-1) EO of A. triphylla to evaluate time of induction and recovery from anesthesia. In another experiment, both strains were divided into four groups such as 0 (control), 30, 40, or 50 μL L(-1) EO and transported for 5 h. The longest time for anesthetic induction and recovery was observed in the albinos. Both strains reached anesthesia in the 100-800 μL L(-1) (11.1-1.24 min) range, without mortality, being 200 μL L(-1) the best response considering time to anesthesia (5.35 min). Albinos transported with all EO concentrations showed higher values of carbon dioxide in the water of transport, but lower levels were observed in grays transported with 40 and 50 μL L(-1) EO when compared to control fish. The same concentrations did not prevent significant whole-body cortisol rise at the end of transport in the albino strain. Juveniles of both strains transported with EO presented lower ion loss to the water compared to control fish. The EO of A. triphylla is an effective anesthetic for albino and gray silver catfish. This EO increases whole-body cortisol levels in the albino strain, but as it reduces net ion loss as in the gray strain, it can be also recommended for transport.


Speciation: Genomic Archipelagos in a Crater Lake.
The opening stages of speciation remain poorly understood, especially from a genomic perspective. The genomes of newly discovered crater-lake cichlid fish shed light on the early phases of diversification and suggest that selection acts on multiple genomic regions.


[Storage technique on artificial seeds of Pinellia ternata].
To study the storage technique on artificial seeds of Pinellia ternata. Microtubers were used as experiment materials. By using orthogonal experiment, the sodium alginate, added with GA3 badistan, chitosan and sodium benzoate, was used as seed vessel. The artificial seeds were stored respectively under 25 degrees C and 4 degrees C for 30 days, then, calculated the germination rate. The sodium alginate(3%) added with GA3(0.1 mg x L(-1)), sodium benzoate(0.2%), badistan(1.0%), ClO2(0.1%) and chitosan(0.2%), were used as artificial seed vessel. Stored under (25 +/- 1) degrees C for 30 days, and the germination rate was over 65%. The sodium alginate(3%), added with GA3(0.1 mg x L(-1)), sodium benzoate(0.2%), badistan(1.0%), ClO2(0.2%) and chitosan(0.1%), were used as artificial seed vessel. Stored under 4 degrees C for 30 days, and the germination rate was over 80%.


Immunohistochemical study of Ia antigen in the normal and diseased human kidney.
The presence and distribution of Ia antigen in normal human kidneys and biopsy specimens from patients with renal disease were investigated by immunohistochemical techniques using two monoclonal antibodies to the nonpolymorphic determinants of human HLA-DR molecules. Ia antigen was found on the endothelium of glomerular and peritubular capillaries and of veins and vasa recta. Loss of endothelial staining was found in necrotic and sclerotic glomerular and tubulointerstitial lesions. Staining or decreased staining was also not found in the severe proliferative nephritis of systemic lupus erythematosus although endothelial cells could still be identified upon light microscopic examination of the same biopsy specimen. Resting and proliferating cells in mesangial areas did not stain with anti-Ia antibody and extracapillary proliferating cells did not express Ia antigen except for occasional cells in anti-GBM crescentic glomerulonephritis, suggesting that Ia-bearing cells are not involved in mesangial and most extracapillary proliferations in human glomerulonephritis. All clustered mononuclear cells infiltrating the renal interstitium stained with anti-Ia antibody regardless of the type of nephritis where infiltrates occurred.


Insulin-degrading enzyme ablation in mouse pancreatic alpha cells triggers cell proliferation, hyperplasia and glucagon secretion dysregulation.
Type 2 diabetes is characterised by hyperglucagonaemia and perturbed function of pancreatic glucagon-secreting alpha cells but the molecular mechanisms contributing to these phenotypes are poorly understood. Insulin-degrading enzyme (IDE) is present within all islet cells, mostly in alpha cells, in both mice and humans. Furthermore, IDE can degrade glucagon as well as insulin, suggesting that IDE may play an important role in alpha cell function in vivo. We have generated and characterised a novel mouse model with alpha cell-specific deletion of Ide, the A-IDE-KO mouse line. Glucose metabolism and glucagon secretion in vivo was characterised; isolated islets were tested for glucagon and insulin secretion; alpha cell mass, alpha cell proliferation and α-synuclein levels were determined in pancreas sections by immunostaining. Targeted deletion of Ide exclusively in alpha cells triggers hyperglucagonaemia and alpha cell hyperplasia, resulting in elevated constitutive glucagon secretion. The hyperglucagonaemia is attributable in part to dysregulation of glucagon secretion, specifically an impaired ability of IDE-deficient alpha cells to suppress glucagon release in the presence of high glucose or insulin. IDE deficiency also leads to α-synuclein aggregation in alpha cells, which may contribute to impaired glucagon secretion via cytoskeletal dysfunction. We showed further that IDE deficiency triggers impairments in cilia formation, inducing alpha cell hyperplasia and possibly also contributing to dysregulated glucagon secretion and hyperglucagonaemia. We propose that loss of IDE function in alpha cells contributes to hyperglucagonaemia in type 2 diabetes.


Comparative study of postoperative complications after radical cystectomy during the past two decades in Japan: Radical cystectomy remains associated with significant postoperative morbidities.
During the past 2 decades, in order to improve perioperative and oncological outcomes, a minimally invasive approach, neoadjuvant chemotherapy (NAC), and an enhanced postoperative recovery program after surgery have been introduced into routine clinical practice of radical cystectomy (RC). Our aim was to examine the differences in clinical practice and postoperative complications after RC by comparing our previous and current cohorts. A retrospective multi-institutional study. We collected all complications within 90 days after surgery between 2011 and 2017 (current cohort), and categorized them according to a standardized methodology. Then, we compared the outcomes with those in our previous study (previous cohort, 1997-2010). A multivariate logistic regression model was utilized to determine predictors of complications in the current cohort. A total of 838 patients were newly collected (current cohort), and 919 from the previous cohort were included in the subsequent analyses. In the current cohort, the rate of performing NAC was significantly higher (13% vs. 4%, respectively, P < 0.0001), and 26% (222/838) underwent laparoscopic RC (LRC, without robotic assistance: n = 210, with robotic assistance: n = 12). There was no significant difference in the overall complication [69% (580/838) vs. 68% (629/919), respectively, P = 0.7284] or major complication (Grades 3-5) [25% (211/838) vs. 22% (201/919), respectively, P = 0.1022] rates between the 2 cohorts. In both cohorts, the most frequent categories were infectious, gastrointestinal, wound-related, and genitourinary. In the current cohort, the performance status (odds ratio, OR = 2.11, P = 0.0013) and operative time (OR = 1.003, P = 0.0016) remained significant predictors of major complications. NAC was not associated with any or major complications. Surgical complications related to RC still remain significant problems, despite the recent improvements in surgical techniques and perioperative care. NAC did not increase the complications.


Comparison of Higher Order Aberrations between Wavefront Optimized Photorefractive Keratectomy and Laser in situ Keratomileusis in Myopic Patients.
To compare the higher order aberrations (HOA) between wavefront optimized (WFO) laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) in myopic patients. Quasi-experimental study. Place and Duration of the Study: Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan, from December 2021 to December 2022. Forty-four patients underwent wavefront optimized PRK and fifty-seven patients underwent wavefront optimized LASIK. All variables were recorded before the procedure and at 1, 3, 6, and 12 months postoperatively and included uncorrected visual acuity (UCVA), corrected distance visual acuity (CDVA), root mean square (RMS) of HOAs, spherical aberration (SA), and coma aberration (CA). A total of 101 eyes of 51 patients were considered in the final analysis. Patients were divided into two groups. Group A comprised of 44 (43.6%) eyes of 22 patients who underwent PRK while group B comprised of 57 (56.4%) eyes of 29 patients who underwent LASIK. UCVA significantly improved postoperatively at 3 and 6 months in both PRK and LASIK groups (p<0.001 for both groups). In this study, the increase in root mean square (RMS) of higher order aberrations from baseline value was 77% after PRK and 28% after LASIK, similar ratio was observed in spherical aberration (SA). The trend of rise in Coma aberrations was more in LASIK group 66.49% as compared to 46.2% in PRK group. Both Wavefront Optimized PRK and LASIK are safe and have elicited comparable results of post-procedure visual recovery. There was a marked increase in RMS of HOAs in PRK group as compared to WFO LASIK group while coma aberration increased more in LASIK as compared to PRK postoperatively. LASIK, PRK, RMSh, HOAs, Spherical aberration, Coma, Myopia.


Verdazyl Radical, a Building Block for a Six-Spin-Center 2p-3d-4f Single-Molecule Magnet.
The versatile verdazyl family provides a new member as its reduced form 1,5-dimethyl-3-[3'-(hydroxymethyl)-2'-pyridine]-6-oxotetrazane (H3vdpyCH2OH). Upon oxidation and deprotonation in the presence of the acetate salts of CoII and DyIII, the vdpyCH2OH radical is able to self-assemble [(vdpyCH2O)2Co2Dy2ac8] (Hac = HO2CCH3), a 2p-3d-4f cluster displaying single-molecule-magnet properties.


Synthesis of new pyrimidine-fused derivatives as potent and selective antidiabetic α-glucosidase inhibitors.
The synthesis of a set of pyrimidine-fused derivatives (L1-L8), resulting from the incorporation of different fragments on the pyrimidine-fused heterocycle (PFH) of the earlier reported α-glucosidase (α-Gls) inhibitor (C1-C5), allowed the discovery of new ligands with modest and selective inhibitory activity. The PFH core (substructure 2) was proved to play a significant role in their inhibitory properties. Additionally, the substituent on substructures 1 and 3 of the heterocyclic ring was demonstrated to be important in the enzyme inhibitory action of the pyrimidine-fused derivatives. Moreover, these ligands show selective inhibitory properties for α-Gls over porcine pancreatic α-amylase (α-Amy) which is important in terms of their reduced susceptibility for the possible development of intestinal disturbance side effects. Therefore, low to moderate α-Amy inhibition with effective α-Gls inhibitory action may offer a better therapeutic strategy. Overall, these compounds can potentially offer a new opportunity to develop novel antidiabetic drugs with selective inhibitory action against α-Gls.


Cytochrome P-450 and halothane metabolism. Decrease in rat liver microsomal P-450 in vitro.
Anaerobic in vitro incubation of microsomes from phenobarbital(PB)-induced rats with halothane results in an irreversible decrease of measurable cytochrome P-450. There is a parallel decrease in heme content under the same incubation conditions. However, microsomes from 3-methylcholanthrene(3-MC)-induced or untreated animals do not show a reduction in cytochrome P-450 content. Aerobic incubation with halothane results in a decrease of cytochrome P-450 which can be completely reversed by dialysis or the addition of potassium ferricyanide. These latter treatments only partially restore the cytochrome P-450 levels following anaerobic incubations. The decrease in cytochrome caused by halothane is not associated with measureable heme N-alkyl adduct formation; lipid peroxidation does not play a role as indicated by the lack of effect of 1 mM EDTA or a decrease in glucose-6-phosphatase activity. Halothane metabolites are bound irreversibly to microsomal protein as determined by gel electrophoresis only when the oxygen concentration is very low. The mechanism of cytochrome P-450 decrease is consistent with the formation of a reactive metabolite which binds to the protein portion and also destroys heme.


Marinifilum flexuosum sp. nov., a new Bacteroidetes isolated from coastal Mediterranean Sea water and emended description of the genus Marinifilum Na et al., 2009.
A facultatively anaerobe, moderately halophilic, Gram-negative, filamentous, non motile and unpigmented bacterium, designated M30(T), was isolated from coastal Mediterranean Sea water in Valencia, Spain. Phylogenetic analysis based on 16S rRNA sequences placed this strain in the phylum "Bacteroidetes" with Marinifilum fragile JC2469(T) as its closest relative with 97% sequence similarity. Average nucleotide identity (ANI) values between both strains were far below the 95% threshold value for species delineation (about 89% using BLAST and about 90% using MUMmer). A comprehensive polyphasic study, including morphological, biochemical, physiological, chemotaxonomic and phylogenetic data, confirmed the independent species status of strain M30(T) within the genus Marinifilum, for which the name Marinifilum flexuosum sp. nov. is proposed. The type strain of Marinifilum flexuosum is M30(T) (=CECT 7448(T)=DSM 21950(T)).


Effectiveness of 5-Fluorouracil and gemcitabine hydrochloride loaded iron‑based chitosan-coated MIL-100 composite as an advanced, biocompatible, pH-sensitive and smart drug delivery system on breast cancer therapy.
This study was planned to evolve the bioavailability and therapeutic efficiency of Gemcitabine (GEM) and 5-Fluorouracil with decreased side effects using MIL-100 nano-composite as carrier. Impregnation approach was used for encapsulation of 5-Fluorouracil alone and with GEM inside the MIL-100. The formed 5-Fluorouracil@MIL-100 and 5-Fluorouracil-GEM@MIL-100 were then coated with chitosan, sequentially chelated with iron(III) and conjugated with quercetin, eventually obtaining a multifunctional MIL-100 nanocarrier. The hybrid nanocarrier nascency was verified by different characterization results. pH-sensitive releases of 5-Fluorouracil and GEM were observed because of the inherent pH-dependent stability of MIL-100. Additionally, we evaluated the anti-cancer activity of these nanocarriers through WST-1 analysis and acridine orange staining in MCF-7 human breast cancer and HUVEC control cell lines. Our findings showed that all nanocarriers exhibited anti-cancer activity and induced apoptosis in MCF-7 cells. However, 5-Fluorouracil@MIL-100 and chitosan-coated 5-Fluorouracil@MIL-100 with quercetin were more effective than other nanocarriers in MCF-7 cells (p < 0.05). Moreover, we observed cytotoxicity in HUVEC cells due to the adverse side effects of chemotherapy drugs. However, chitosan coated nanocarriers with quercetin were less toxic on HUVEC cells at particularly 1 µg/mL. Therefore, MIL-100 could be used for a promising chemotherapeutic drugs delivery and chitosan coated drugs with quercetin could be useful for reducing toxicity on normal cells.


Regulation of maxi-K+ channels on pancreatic duct cells by cyclic AMP-dependent phosphorylation.
Using the patch-clamp technique we have identified a Ca2(+)-sensitive, voltage-dependent, maxi-K+ channel on the basolateral surface of rat pancreatic duct cells. The channel had a conductance of approximately 200 pS in excised patches bathed in symmetrical 150 mM K+, and was blocked by 1 mM Ba2+. Channel open-state probability (Po) on unstimulated cells was very low, but was markedly increased by exposing the cells to secretin, dibutyryl cyclic AMP, forskolin or isobutylmethylxanthine. Stimulation also shifted the Po/voltage relationship towards hyperpolarizing potentials, but channel conductance was unchanged. If patches were excised from stimulated cells into the inside-out configuration, Po remained high, and was not markedly reduced by lowering bath (cytoplasmic) Ca2+ concentration from 2 mM to 0.1 microM. However, activated channels were still blocked by 1 mM Ba2+. Channel Po was also increased by exposing the cytoplasmic face of excised patches to the purified catalytic subunit of cyclic AMP-dependent protein kinase. We conclude that cyclic AMP-dependent phosphorylation can activate maxi-K+ channels on pancreatic duct cells via a stable modification of the channel protein itself, or a closely associated regulatory subunit, and that phosphorylation alters the responsiveness of the channels to Ca2+. Physiologically, these K+ channels may contribute to the basolateral K+ conductance of the duct cell and, by providing a pathway for current flow across the basolateral membrane, play an important role in pancreatic bicarbonate secretion.


Determination of hymexazol in cucumber and soil samples by derivatization using GC-FPD.
A sensitive and effective analytical method for the determination of hymexazol in cucumber and soil samples by gas chromatography with a flame photometric detector was developed. This method was validated with fortified at three different levels of 0.2, 1.0 and 5.0 mg/kg. Average recoveries obtained from cucumber and soil samples at three fortified levels were 94.0%-107.8% with relative standard deviations (RSDs) of less than 11.4%. Limits of quantification (LOQ) in cucumber and soil were 0.2 mg/kg. The method was successfully applied to determine hymexazol in real samples of cucumber and soil under open fields.


Status of pesticides pollution in Tanzania - A review.
Various studies have been conducted in Tanzania to assess the magnitude of pesticides pollution associated with pesticides application, storage, disposal as well as knowledge of farmers on pesticides handling. The studies analysed samples from different matrices covering vegetation, biota, water, sediments and soil. The objective of this review was to summarise the results of pesticides residues reported in different components of the environment to give a clear picture of pesticides pollution status in the country for law enforcement as well as for taking precaution measures. Gaps which need to be filled in order to establish a comprehensive understanding on pesticides pollution in the country have also been highlighted. Reviewed studies revealed that, most of the samples contained pesticides below permissible limits (WHO, FAO, US-EPA) except for few samples such as water from Kikavu river, Kilimanjaro region and Kilolo district, Iringa region which were detected with some Organochlorine pesticides (OCPs) above WHO permissible limits. Some soil samples from the former storage sites also contained pesticides above FAO permissible limits. Pesticides and their metabolites were also detected both in vegetation, food and biota samples. The prevalent pesticides in the reviewed studies were the organochlorines such as Dichlorodiphenyltrichloroethane (DDT), endosulfan and Hexachlorocyclohexane (HCH). Surveys to assess farmer's knowledge on pesticides handling observed poor understanding of farmers on pesticides storage, application and disposal. Decontamination of former storage areas, continuous monitoring of pesticide applications and training of farmers on proper handling of pesticides are highly recommended.


Acute inorganic nitrate supplementation and the hypoxic ventilatory response in patients with obstructive sleep apnea.
Patients with obstructive sleep apnea (OSA) have increased cardiovascular disease risk largely attributable to hypertension. Heightened peripheral chemoreflex sensitivity (i.e., exaggerated responsiveness to hypoxia) facilitates hypertension in these patients. Nitric oxide blunts the peripheral chemoreflex, and patients with OSA have reduced nitric oxide bioavailability. We therefore investigated the dose-dependent effects of acute inorganic nitrate supplementation (beetroot juice), an exogenous nitric oxide source, on blood pressure and cardiopulmonary responses to hypoxia in patients with OSA using a randomized, double-blind, placebo-controlled crossover design. Fourteen patients with OSA (53 ± 10 yr, 29.2 ± 5.8 kg/m2, apnea-hypopnea index = 17.8 ± 8.1, 43%F) completed three visits. Resting brachial blood pressure and cardiopulmonary responses to inspiratory hypoxia were measured before, and 2 h after, acute inorganic nitrate supplementation [∼0.10 mmol (placebo), 4.03 mmol (low dose), and 8.06 mmol (high dose)]. Placebo increased neither plasma [nitrate] (30 ± 52 to 52 ± 23 μM, P = 0.26) nor [nitrite] (266 ± 153 to 277 ± 164 nM, P = 0.21); however, both increased following low (29 ± 17 to 175 ± 42 μM, 220 ± 137 to 514 ± 352 nM) and high doses (26 ± 11 to 292 ± 90 μM, 248 ± 155 to 738 ± 427 nM, respectively, P < 0.01 for all). Following placebo, systolic blood pressure increased (120 ± 9 to 128 ± 10 mmHg, P < 0.05), whereas no changes were observed following low (121 ± 11 to 123 ± 8 mmHg, P = 0.19) or high doses (124 ± 13 to 124 ± 9 mmHg, P = 0.96). The peak ventilatory response to hypoxia increased following placebo (3.1 ± 1.2 to 4.4 ± 2.6 L/min, P < 0.01) but not low (4.4 ± 2.4 to 5.4 ± 3.4 L/min, P = 0.11) or high doses (4.3 ± 2.3 to 4.8 ± 2.7 L/min, P = 0.42). Inorganic nitrate did not change the heart rate responses to hypoxia (beverage-by-time P = 0.64). Acute inorganic nitrate supplementation appears to blunt an early-morning rise in systolic blood pressure potentially through suppression of peripheral chemoreflex sensitivity in patients with OSA.NEW & NOTEWORTHY The present study is the first to examine the acute effects of inorganic nitrate supplementation on resting blood pressure and cardiopulmonary responses to hypoxia (e.g., peripheral chemoreflex sensitivity) in patients with obstructive sleep apnea (OSA). Our data indicate inorganic nitrate supplementation attenuates an early-morning rise in systolic blood pressure potentially attributable to blunted peripheral chemoreflex sensitivity. These data show proof-of-concept that inorganic nitrate supplementation could reduce the risk of cardiovascular disease in patients with OSA.


Cutaneous adverse reactions to clindamycin: results of skin tests and oral exposure.
Clindamycin is an antibiotic used in anaerobic and severe complicated infections. It is often selected for patients with a history of allergy to other antibiotics. To study the occurrence of clindamycin hypersensitivity and to determine whether skin tests are useful in cases of suspected clindamycin allergy. Six patients with an exanthematous rash and a history strongly suggestive of clindamycin hypersensitivity were studied with skin tests and oral exposure. Cases of suspected adverse drug reactions to clindamycin reported to the National Register of Adverse Effects of Drugs (NRAED) in Finland during 1973-2000 were analysed. In the skin tests true-positive patch test reactions were seen in four of six patients, while 22 healthy control patients were negative. One false-positive and one false-negative patch test reaction were seen. During 1973-2000, 29 suspected cases of skin and/or mucosal membranes affected by clindamycin were reported to the NRAED. Clindamycin hypersensitivity is not common. Delayed-type allergic reactions occur and patch tests are useful in those cases. Oral exposure is the method of choice if possible, as false-negative and false-positive reactions may occur.


Evaluation of measurement uncertainties of an analytical method for the determination of aflatoxin M1 in milk and milk powder.
The mycotoxin aflatoxin M1 (AfM1) is a serious food safety hazard for which the European Commission has already established a maximum permissible level of 0.05 μg/kg AfM1 in milk and products thereof. For control analysis laboratories are increasingly asked to submit full uncertainties of their analytical results.The evaluation of measurement uncertainties of an analytical method for the determination of AfM1 in milk and milk powder on the basis of 'in-house' validation data in compliance with the 'Guide to the Expression of Uncertainty in Measurement (GUM)' [1] and the 'EURACHEM Guide' [2] is described. A similar approach will be used to assess the performance of methods employed by laboratories participating in the certification of reference materials for AfM1 in milk powder.


Bacterial cysteine conjugate beta-lyase and the metabolism of cysteine S-conjugates: structural requirements for the cleavage of S-conjugates and the formation of reactive intermediates.
The cysteine conjugate beta-lyase mediated metabolism and the mutagenicity of the synthetic cysteine conjugates S-(2-chloroethyl)-L-cysteine (CEC), S-(2-chlorovinyl)-L-cysteine (CVC), S-(1,2,3,3,3-pentachloroprop-1-enyl)-L-cysteine (PCPC), S-(pentachlorophenyl)-L-cysteine (PCPhC), S-(chloro-1,2,2-trifluoroethyl)-L-cysteine (CTFEC), S-benzyl-L-cysteine (SBC) and S-methyl-L-cysteine (SMC) were investigated in Salmonella typhimurium strains TA100, TA2638, TA102 and TA98 to establish structure/activity relationships. Bacterial 100,000 X g supernatants cleaved CTFEC, PCPC, CVC, PCPhC and SBC to pyruvate; pyruvate formation was inhibited by the beta-lyase inhibitor aminooxyacetic acid (AOAA) in all cases. Of the compounds tested, CEC, PCPC and CVC were mutagenic in the Ames-test. CTFEC, PCPhC and SBC failed to increase the number of revertants above control levels. The mutagenicity of PCPC and CVC could be inhibited by AOAA. CEC exerted a potent mutagenic effect in the Ames-test which was not affected by AOAA; CEC was not transformed to pyruvate by bacterial beta-lyase. Neither pyruvate formation nor mutagenicity were observed with SMC. These results indicate that the structure of the substituent on the sulfur atom is an important determinant for the biological activity of cysteine S-conjugates. Electronegative and/or unsaturated substituents are required for beta-lyase catalysed beta-elimination reactions. The formation of chemically unstable thiols, which may be converted to thioacylating intermediates, seems to be a prerequisite for beta-lyase dependent mutagenicity of S-conjugates.


Alterations in both excitation and inhibition occur before the onset of seizure activity in the hippocampus.
Excitatory and inhibitory mechanisms have been implicated in the onset of seizures and as underlying kindling. In this study, changes in responses to single stimuli and paired pulse stimuli were used to monitor postsynaptic excitability before the onset of seizure activity in limbic circuits of urethane-anesthetized rats. With sufficient stimulus intensity, a stimulus paradigm of seven pulses every second for 10 s led to seizure activity, as indicated by the appearance of maximal dentate activation, and afterdischarges. An increase in the evoked response was found in both CA1 and the dentate gyrus during stimulus trains to either CA3 or the angular bundle and there was the appearance of a polysynaptic response. There was an increase in paired pulse inhibition in the dentate gyrus and a decrease in paired pulse inhibition in the CA1 region during the stimulus protocol. Since repeated seizures and a number of pharmacological agents are known to alter the onset and duration of seizure activity, a relationship between the changes in excitability and the onset of the seizure activity was tested using MK-801, ketamine, bicuculline, diazepam, phenobarbital, baclofen and repeated seizures. Overall, alteration of the amplitude of the polysynaptic response in CA1 to angular bundle stimulation correlated best with the effects of the drugs and the seizures on the duration of maximal dentate activation.


Evidence for intriguingly complex transcription of human thioredoxin reductase 1.
Human thioredoxin reductase 1 (TrxR1, the TXNRD1 gene product) is a ubiquitously expressed selenoprotein with many important redox regulatory functions. In this study, we have further characterized the recently identified core promoter region of TXNRD1. One critical Sp1/Sp3 site was found to be important in A549 and HeLa cells, whereas another Sp1/Sp3 site and one Oct1 site bound transcription factors but were, nonetheless, dispensable for transcription. We also experimentally identified several 5'-region TXNRD1 transcript variants using 5'-RACE with cDNA derived from different tissues, and we analyzed all available TXNRD1-derived EST sequences. The results show that the core promoter governs transcription of the clear majority of TXNRD1 transcripts but also that alternative promoters may be activated under rare conditions or in specific cell types. Furthermore, extensive alternative splicing occured in the 5' region of TXNRD1. In total, 21 different transcripts were identified, potentially encoding five isoforms of TrxR1 carrying alternative N-terminal domains. One isoform encompassed a glutaredoxin domain, whereas another encoded a predicted mitochondrial localization signal. These results reveal that the human thioredoxin system is intriguingly complex. Cell-specific transcription of the TXNRD1 gene encoding different isoforms of TrxR1 must be taken into account to fully understand the functions of the human thioredoxin system.


Early reconstruction of wide ureter in children.
Fifty children with 66 megaureters have been treated with complete surgical reconstruction and reimplantation of the ureter. The procedure was done unilaterally in 34 and bilaterally in 16 patients. Fourteen of the bilateral cases were corrected in one procedure. The results in the reported series seem to justify the conclusion that early reconstruction forms a ureter which is neither wide, nor elongated, nor tortuous and thus able to transport urine.


Efficient platform for synthesizing comprehensive heparan sulfate oligosaccharide libraries for decoding glycosaminoglycan-protein interactions.
Glycosaminoglycans (GAGs) are abundant, ubiquitous carbohydrates in biology, yet their structural complexity has limited an understanding of their biological roles and structure-function relationships. Synthetic access to large collections of well defined, structurally diverse GAG oligosaccharides would provide critical insights into this important class of biomolecules and represent a major advance in glycoscience. Here we report a new platform for synthesizing large heparan sulfate (HS) oligosaccharide libraries displaying comprehensive arrays of sulfation patterns. Library synthesis is made possible by improving the overall synthetic efficiency through universal building blocks derived from natural heparin and a traceless fluorous tagging method for rapid purification with minimal manual manipulation. Using this approach, we generated a complete library of 64 HS oligosaccharides displaying all possible 2-O-, 6-O- and N-sulfation sequences in the tetrasaccharide GlcN-IdoA-GlcN-IdoA. These diverse structures provide an unprecedented view into the sulfation code of GAGs and identify sequences for modulating the activities of important growth factors and chemokines.


Adjusting multiple testing in multilocus analyses using the eigenvalues of a correlation matrix.
Correlated multiple testing is widely performed in genetic research, particularly in multilocus analyses of complex diseases. Failure to control appropriately for the effect of multiple testing will either result in a flood of false-positive claims or in true hits being overlooked. Cheverud proposed the idea of adjusting correlated tests as if they were independent, according to an 'effective number' (M(eff)) of independent tests. However, our experience has indicated that Cheverud's estimate of the Meff is overly large and will lead to excessively conservative results. We propose a more accurate estimate of the M(eff), and design M(eff)-based procedures to control the experiment-wise significant level and the false discovery rate. In an evaluation, based on both real and simulated data, the M(eff)-based procedures were able to control the error rate accurately and consequently resulted in a power increase, especially in multilocus analyses. The results confirm that the M(eff) is a useful concept in the error-rate control of correlated tests. With its efficiency and accuracy, the M(eff) method provides an alternative to computationally intensive methods such as the permutation test.


Adatom mediated adsorption of N-heterocyclic carbenes on Cu(111) and Au(111).
The adsorption of N-heterocyclic carbenes (NHCs) on Cu(111) and Au(111) surfaces is studied with density-functional theory. The role of the molecular side groups as well as the surface morphology in determining the adsorption geometry are explored in detail. Flat-laying NHCs, as observed experimentally for NHC with relatively small side groups, result from the adsorption at adatoms and give rise to the so-called ballbot configurations, which are more stable than adsorption on flat surfaces and provide an efficient precursor for the formation of bis(NHC) dimers. On Au(111), the resulting (NHC)2 Au complexes are purely physisorbed and thus mobile. On the more reactive Cu(111), in contrast, the central Cu atom in the (NHC)2 Cu dimer is still covalently bound to the surface, resulting in a mobility, which has to be thermally activated.


Ex vivo rectal explant model reveals potential opposing roles of Natural Killer cells and Marginal Zone-like B cells in HIV-1 infection.
Our understanding of innate immune responses in human rectal mucosal tissues (RM) and their contributions to promoting or restricting HIV transmission is limited. We defined the RM composition of innate and innate-like cell subsets, including plasmacytoid dendritic cells; CD1c + myeloid DCs; neutrophils; macrophages; natural killer cells (NK); Marginal Zone-like B cells (MZB); γδ T cells; and mucosal-associated invariant T cells in RM from 69 HIV-negative men by flow cytometry. Associations between these cell subsets and HIV-1 replication in ex vivo RM explant challenge experiments revealed an inverse correlation between RM-NK and p24 production, in contrast to a positive association between RM-MZB and HIV replication. Comparison of RM and blood-derived MZB and NK illustrated qualitative and quantitative differences between tissue compartments. Additionally, 22 soluble molecules were measured in a subset of explant cultures (n = 26). Higher production of IL-17A, IFN-γ, IL-10, IP-10, GM-CSF, sFasL, Granzyme A, Granzyme B, Granulysin, and Perforin following infection positively correlated with HIV replication. These data show novel associations between MZB and NK cells and p24 production in RM and underscore the importance of inflammatory cytokines in mucosal HIV infection, demonstrating the likely critical role these innate immune responses play in early mucosal HIV replication in humans.


Interferon gamma allelic variants: sex-biased multiple sclerosis susceptibility and gene expression.
Interferon (IFN) gamma (IFNG) allelic variants are associated with susceptibility to multiple sclerosis (MS) in men but not in women. To conduct a high-density linkage disequilibrium association study of IFNG and the surrounding region for sex-associated MS susceptibility bias and to evaluate whether IFNG allelic variants associated with MS susceptibility are associated with expression. Genotype case-control study, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay expression analyses for IFN gamma. Three independently ascertained populations from the Mayo Clinic, Rochester, Minnesota, Queen's University of Belfast, Belfast, Ireland, and University of Leuven, Leuven, Belgium. For linkage disequilibrium, 861 patients with MS (293 men and 568 women) and 843 controls (340 men and 503 women) derived from the US (population-based) and the Northern Ireland and Belgium (clinic-based) cohorts were studied. For expression analyses, 50 US patients were selected to enrich for homozygotes and to achieve a balance between men and women. Twenty markers were genotyped over the 120-kilobase region harboring IFNG and the interleukin 26 gene (IL26). Expression of IFN gamma was evaluated by qPCR and enzyme-linked immunosorbent assay in stimulated peripheral blood mononuclear cells. Multiple markers were associated with MS susceptibility in men but not in women. The sex-specific susceptibility markers, of which rs2069727 was the strongest, were confined to IFNG. Carriers of rs2069727*G had higher expression than noncarriers. The effect of genotype in the qPCR experiments was also evident in men but not in women. IFNG is associated with sex bias in MS susceptibility and with expression of IFN gamma in MS. These observations add to a growing body of literature that implicates an interaction between sex and IFN gamma expression in a variety of disease states.


Molecular characterization of a cold-induced plasma membrane protein gene from wheat.
As a means to study the function of plasma membrane proteins during cold acclimation, we have isolated a cDNA clone for wpi6 which encodes a putative plasma membrane protein from cold-acclimated winter wheat. The wpi6 gene encodes a putative 5.9 kDa polypeptide with two predicted membrane-spanning domains, the sequence of which shows high sequence similarity with BLT101-family proteins from plants and yeast. Strong induction of wpi6 mRNA was observed during an early stage of cold acclimation in root and shoot tissues of both winter and spring wheat cultivars. In contrast to blt101 in barley, wpi6 mRNA was also induced by drought and salinity stresses, and exogenous application of ABA. Expression of wpi6 in a Deltapmp3 mutant of Saccharomyces cerevisiae, which is disturbed in plasma membrane potential due to the lack of a BLT101-family protein, partially complemented NaCl sensitivity of the mutant. Transient expression analysis of a WPI6::GFP fusion protein in onion epidermal cells revealed that WPI6 is localized in the plasma membrane. Taken together, these data suggested that WPI6 may have a protective role in maintaining plasma membrane function during cold acclimation in wheat.


Mutual augmentation of the induction of the histamine-forming enzyme, histidine decarboxylase, between alendronate and immuno-stimulants (IL-1, TNF, and LPS), and its prevention by clodronate.
Nitrogen-containing bisphosphonates (N-BPs), powerful anti-bone-resorptive drugs, have inflammatory side effects, while histamine is not only an inflammatory mediator, but also an immuno-modifier. In murine models, a single intraperitoneal injection of an N-BP induces various inflammatory reactions, including the induction of the histamine-forming enzyme histidine decarboxylase (HDC) in tissues important in immune responses (such as liver, lungs, spleen, and bone marrow). Lipopolysaccharide (LPS) and the proinflammatory cytokines IL-1 and TNF are also capable of inducing HDC. We reported previously that in mice, (i) the inflammatory actions of N-BPs depend on IL-1, (ii) N-BP pretreatment augments both LPS-stimulated IL-1 production and HDC induction, and (iii) the co-administration of clodronate (a non-N-BP) with an N-BP inhibits the latter's inflammatory actions (including HDC induction). Here, we add the new findings that (a) pretreatment with alendronate (a typical N-BP) augments both IL-1- and TNF-induced HDC elevations, (b) LPS pretreatment augments the alendronate-induced HDC elevation, (c) co-administration of clodronate with alendronate abolishes these augmentations, (d) alendronate does not induce HDC in IL-1-deficient mice even if they are pretreated with LPS, and (e) alendronate increases IL-1beta in all tissues tested, but not in the serum. These results suggest that (1) there are mutual augmentations between alendronate and immuno-stimulants (IL-1, TNF, and LPS) in HDC induction, (2) tissue IL-1beta is important in alendronate-stimulated HDC induction, and (3) combination use of clodronate may have the potential to reduce the inflammatory effects of alendronate (we previously found that clodronate, conveniently, does not inhibit the anti-bone-resorptive activity of alendronate).


Rhabdomyosarcoma and undifferentiated sarcoma in the first two decades of life: a selective review of intergroup rhabdomyosarcoma study group experience and rationale for Intergroup Rhabdomyosarcoma Study V.
To review the importance of prognostic factors in developing new protocols for children with rhabdomyosarcoma (RMS). Four studies conducted by the Intergroup Rhabdomyosarcoma Study (IRS) Group from 1972 through 1991. Favorable prognostic factors are: (1) undetectable distant metastases at diagnosis; (2) primary sites in the orbit and nonparameningeal head/neck and genitourinary nonbladder/prostate regions; (3) grossly complete surgical removal of localized tumor at the time of diagnosis; (4) embryonal/botryoid histology; (5) tumor size < or = 5 cm; and (6) age younger than 10 years at diagnosis. The IRS-V protocols are risk-based and refine therapy by reducing exposure to cyclophosphamide and radiation therapy (XRT) in patients at low risk while adding new, active agents such as topotecan or irinotecan to the standard therapy of vincristine, actinomycin D, and cyclophosphamide (VAC) plus XRT for patients with unfavorable histology or advanced disease. Collection of biologic specimens from patients with newly diagnosed disease continues to identify other factors that may distinguish patients with favorable features from those who need more intensive therapy. A new protocol that takes into account their previous treatment is needed for patients with recurrent disease. This program (being planned) does not include bone marrow/stem cell reconstitution because this strategy has thus far failed to improve survival rates of patients with metastases at diagnosis. Better understanding of biologic differences and new, active agents are needed to improve outcome of patients with unfavorable features at presentation.


Solubilized cystatin C amyloid is cytotoxic to cultured human cerebrovascular smooth muscle cells.
Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid within arteries of the cerebral cortex and leptomeninges. This condition is age related, especially prevalent in Alzheimer's disease (AD) and the main feature of certain hereditary disorders. The vascular smooth muscle cells (VSMC) appear to play a vital role in the development of CAA and have been found to produce the amyloid beta precursor protein (AbetaPP) and process it to Abeta the major component of most CAA amyloid. Moreover, synthesized Abeta has proven to be toxic to cerebral VSMC in culture possibly explaining the disintegration and disappearance of the muscle cells from affected cerebral blood vessels seen in CAA. An aggressive and extremely rare form of CAA, known as Hereditary Cerebral Hemorrhage With Amyloidosis-Icelandic Type (HCHWA-I), exhibits this withdrawal of VSMC as amyloid accumulates in the vessel wall. However, the amyloid in HCHWA-I is made from a variant of cystatin C (L68Q) instead of the more common Abeta. To evaluate possible cytotoxicity in this condition solubilized cystatin C amyloid extracted from HCHWA-I leptomeninges was applied to cerebral smooth muscle cells in culture and was found to kill the cells.


Climate change and viral emergence: evidence from Aedes-borne arboviruses.
Climate change is leading to increases in global temperatures and erratic precipitation patterns, both of which are contributing to the expansion of mosquito-borne arboviruses and the populations of the mosquitos that vector them. Herein, we review recent evidence of emergence and expansion of arboviruses transmitted by Aedes mosquitos that has been driven in part by environmental changes. We present as a case study of recent work from Córdoba, Argentina, where dengue has been actively emerging in the past decade. We review recent empirical and modeling studies that aim to understand the impact of climate on future expansion of arboviruses, and we highlight gaps in empirical studies linking climate to arbovirus transmission at regional levels.


Long-term prognostic value of preoperative anemia in patients with colorectal cancer: A systematic review and meta-analysis.
To evaluate the long-term prognostic factor of preoperative anemia in colorectal cancer patients. Anemia is frequently observed in colorectal cancer patients, with a case incidence of 30 to 67 percent. Besides an indicator of tumor-induced blood loss and inflammation, anemia in cancer is also suggested to be a cause of inferior outcome, possibly via worsening of tumor hypoxia. As surgery is likely to enhance anemia, the long-term prognostic value of preoperative anemia seems most interesting. Comprehensive searches were carried out in all relevant databases, including MEDLINE, Embase and Web-of-Science. To include studies addressing overall survival, follow-up had to be at least 24 months or till death. For pooling of survival results, a mixed-linear (fixed-effects) model was fit to the reported hazard ratios (HRs) to calculate a pooled estimate and confidence interval. We included 12 studies comprising 3588 patients to estimate the association between preoperative anemia and overall survival (OS) and disease-free survival (DFS). In a fixed-effects meta-analysis of eight studies, including both colon and rectal cancer, preoperative anemia was significantly associated with poor OS (HR 1.56; 95% CI 1.30 to 1.88; p < 0.001). A meta-analysis of seven studies also showed that preoperative anemia was significantly associated with poor DFS (HR 1.34; 95% CI 1.11 to 1.61; p = 0.002). Restricted to studies exclusively on colon cancer or rectal cancer, HRs for OS were 1.25 (95% CI 1.00 to 1.55; p = 0.05) and 2.59 (95% CI 1.68 to 4.01; p < 0.001), respectively, while HRs for DFS were 1.21 (95% CI 0.96 to 1.52; p = 0.11) and 1.61 (95% CI 1.18 to 2.21; p = 0.003). The present meta-analysis reveals that preoperative anemia is significantly associated with decreased long-term OS and DFS in rectal cancer, but not in colon cancer patients, although this meta-analysis is mainly based on retrospective studies with high heterogeneity. These results justify raised awareness about the impact of preoperative anemia on long-term survival.


Analysis of 200 free flaps.
Two hundred microvascular free flaps which were carried out over a period of 13 years 3 months have been analysed from various points of view. Overall survival rate was 94.8% and incidence of re-exploration was 6%. The conclusion obtained from this survey is very simple, namely, the most important factors for successful free flap transfer are a good anastomosis and a reliable flap monitoring system.


The effect of management factors on the seroprevalence of Anaplasma marginale in Bos indicus cattle in the Mexican tropics.
A cross-sectional study with a two-stage design and proportional distribution was carried out to determine the effect of management factors on the seroprevalence of Anaplasma marginale in Bos indicus cattle in the Mexican tropics. Serum was obtained from 384 cattle aged 1-2 years on 92 farms. The number of samples was proportionally distributed according to the number of farms in eastern Yucatan. Antibody activity against A. marginale was assessed using the card agglutination test. A primary screening using a 2 x K contingency table of the exposed variables with the outcomes was performed. All variables for which p < 0.20 were included in a fixed-effects log regression. The seroprevalence in the cattle was 69.75% (SE +/- 0.02). Sixty-four per cent of the farms had a seroprevalence > or = 75%. The risks related to managemental factors were stocking density ( > or = 1 animal/ha, OR = 10.94), type of acaricide (pyrethroids, OR = 3.8), dipping interval ( > 60 days, OR = 0.13) and type of veterinary instruments used (needles, scalpels, ear tattoos, and dehorners, OR = 0.17).


In Vitro susceptibilities of wild and drug resistant Leishmania donovani amastigotes to piperolactam A loaded hydroxypropyl-β-cyclodextrin nanoparticles.
Leishmaniasis is an epidemic in various countries, and the parasite Leishmania donovani is developing resistance against available drugs. In the present study the antileishmanial action of piperolactam A (PL), isolated after bioactivity guided fractionation from root extracts of Piper betle was accentuated in detail. Activity potentiation was achieved via cyclodextrin complexation. Crude hydro-ethanolic extract (PB) and three fractions obtained from PB and fabricated PL-hydroxypropyl-β-cyclodextrin (HPBCD) nanoparticles were evaluated for antileishmanial activity. Tests were performed against L. donovani wild-type, sodium stibogluconate, paromomycin and field isolated (GE1) resistant strains in axenic amastigote and amastigote in macrophage models. PL-HPBCD complex was characterized and FITC loaded HPBCD nanoparticles were assessed for macrophage internalization in confocal microscopic studies. Isolated and purified PL from most potent, alkaloid rich ethyl acetate fraction of PB showed high level of antileishmanial activities in wild-type (IC50=36 μM), sodium stibogluconate resistant (IC50=103 μM), paromomycin resistant (IC50=91 μM) and field isolated resistant (IC50=72 μM) strains together with cytotoxicity (CC50=900 μM) in mouse peritoneal macrophage cells. Inclusion of PL in HPBCD nanoparticles resulted in 10-fold and 4-10-fold increase in selectivity indexes (CC50/IC50) for wild-type and drug resistant strains, respectively. Drug-carrier interactions were clearly visualized in FT-IR studies. Complete incorporation of PL in HPBCD cavity was ascertained in DSC and XRD analyses. 180nm size stable nanospheres showed macrophage internalization within 1h of incubation. Piperolactam A (PL), a representative of the inchoate skeleton of aristolactam chassis might be the source of safe and affordable antileishmanial agents for the cure of deadly Leishmania infections.


Echoplanar imaging in GI clinical practice: assessment of gastric emptying and antral motility in four patients.
Gastric emptying, frequency of antral contractions, and speed of antral contraction propagation were assessed in four patients using echoplanar imaging techniques. The results obtained and their impact on the diagnosis and management of the patients are presented and discussed. This shows that echoplanar evaluation of gastric function is noninvasive, well-tolerated by patients, detects clinically relevant abnormalities, and has the potential of becoming a valuable examination in the clinical gastrointestinal practice.


Bioinformatics Research and qRT-PCR Verify Hub Genes and a Transcription Factor-MicroRNA Feedback Network in Intervertebral Disc Degeneration.
The present study explores the potentials of bioinformatics analysis to identify hub genes linked to intervertebral disc degeneration (IDD) and explored the potential molecular mechanism of transcription factor-microRNA regulatory network. Furthermore, the hub genes were identified through quantitative reverse transcriptase PCR (qRT-PCR). GEO database expression profile datasets for candidate genes (GSE124272) were downloaded. Genes that were differentially expressed (DEGs) were detected utilizing limma technique in the R programming language. Search Tool for the Retrieval of Interacting Genes/Proteins and NetworkAnalyst software identified hub genes. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis as well as Gene Ontology annotation of the DEGs were performed using Metascape. Using Bioinformatics data from the TRRUST, StarBase, and TransmiR databases, a TF-miRNA-hub genes network was constructed. qRT-PCR was utilized to confirm the result. As compared to healthy persons, 521 DEGs, comprising 203 down-regulated and 318 up-regulated genes, as well as 7 core genes, were found in people with IDD. Analysis revealed that all seven essential genes were under-expressed. qRT-PCR further confirmed the low expression of these seven important genes. Based on the TRRUST database, 16 TFs that could target five junction genes were then predicted. According to the StarBase database, four miRNAs were linked to crucial genes, while the TransmiR database predicted regulatory connections between four miRNAs and five TFs. The expression of the TP53-(hsa-miR-183-5p)-CCNB1 TF-miRNA-mRNA interaction network was discovered to be correlated with IDD. Throughout this investigation, a network of TF-miRNA-mRNA connections was built for investigation of the probable molecular mechanisms responsible for IDD. The identification of hub genes associated with IDD may reveal promising IDD treatment strategies.


Lichen planopilaris and frontal fibrosing alopecia: review and update of diagnostic and therapeutic features.
Lichen planopilaris and frontal fibrosing alopecia are primary scarring alopecias where diagnosis can be suggested by clinical and trichoscopy features, especially in the early stages, but scalp biopsy is the standard exam for definitive diagnosis. Frontal fibrosing alopecia is considered a variant of lichen planopilaris, as the histopathological findings are similar, with a perifollicular lymphohistiocytic infiltrate, sometimes with a lichenoid pattern. A thorough clinical examination, trichoscopy and photographic documentation are essential to assess the evolution and therapeutic response. To date, there are no validated treatments or guidelines for these diseases, but there are recommendations that vary with the individual characteristics of each patient. This article presents a comprehensive review of the literature, including an update on topics related to the diagnosis, follow-up, histopathological aspects and available treatments for lichen planopilaris and frontal fibrosing alopecia, highlighting their similarities, differences and peculiarities.


Extraction and downstream processing of plant-derived recombinant proteins.
Plants offer the tantalizing prospect of low-cost automated manufacturing processes for biopharmaceutical proteins, but several challenges must be addressed before such goals are realized and the most significant hurdles are found during downstream processing (DSP). In contrast to the standardized microbial and mammalian cell platforms embraced by the biopharmaceutical industry, there are many different plant-based expression systems vying for attention, and those with the greatest potential to provide inexpensive biopharmaceuticals are also the ones with the most significant drawbacks in terms of DSP. This is because the most scalable plant systems are based on the expression of intracellular proteins in whole plants. The plant tissue must therefore be disrupted to extract the product, challenging the initial DSP steps with an unusually high load of both particulate and soluble contaminants. DSP platform technologies can accelerate and simplify process development, including centrifugation, filtration, flocculation, and integrated methods that combine solid-liquid separation, purification and concentration, such as aqueous two-phase separation systems. Protein tags can also facilitate these DSP steps, but they are difficult to transfer to a commercial environment and more generic, flexible and scalable strategies to separate target and host cell proteins are preferable, such as membrane technologies and heat/pH precipitation. In this context, clarified plant extracts behave similarly to the feed stream from microbes or mammalian cells and the corresponding purification methods can be applied, as long as they are adapted for plant-specific soluble contaminants such as the superabundant protein RuBisCO. Plant-derived pharmaceutical proteins cannot yet compete directly with established platforms but they are beginning to penetrate niche markets that allow the beneficial properties of plants to be exploited, such as the ability to produce 'biobetters' with tailored glycans, the ability to scale up production rapidly for emergency responses and the ability to produce commodity recombinant proteins on an agricultural scale.


Nutritional quality of snacks and beverages sold through vending machines in a large Hispanic-serving urban college campus in the United States: A cross-sectional study.
Students from nutritionally-vulnerable neighborhoods face dietary challenges through built environment of college vending machines. In this cross-sectional study, snacks and beverages sold in vending machines for a 4-week period in a Bronx-based Hispanic-serving college were recorded. Nutritional information was recorded from nutrition labels. Proportion of low- and high-sodium foods, "smart snacks" with a limit of 200 kcal and 200 mg of sodium, and foods with added sugar were recorded. Snacks had significantly higher calories and sodium per serving (227 kcal, 208 mg) than beverages (132 kcal, 90 mg) (t-test, p < 0.001). Almost a third of the snacks (32%) qualified as "smart snacks" for calories and 62% qualified as "smart snacks" for sodium. Beverages contained less than half the number of ingredients as snacks. About 53% of beverages and almost 60% of snacks listed sugar among the first five ingredients. Results underscore the need for colleges to promote less-processed entities with less added sugar.


The Effect of instilled fluorescein solution volume on the values and repeatability of TBUT measurements.
To investigate how the volume of instilled fluorescein solution alters invasive tear breakup time (TBUT) and the standard deviation (SD) of multiple recordings, and to determine the volume of fluid supplied by traditional fluorescein-impregnated strips (FS) and a micropipette calibrated to dispense 1 microL. TBUT was measured 3 times in the right eyes of 46 subjects following the instillation of 1, 2.7, and 7.4 microL of fluorescein solution by micropipette and the use of a wetted FS. The volume of fluid delivered to an eye by FS and a micropipette set for 1 microL was estimated by weighing each before and after use. The volume of fluorescein solution instilled before measurement influenced TBUT (P < 0.001). Increasing the delivered volume from 1 to 2.7 microL lengthened TBUT (P < 0.001), but an additional increase in volume to 7.4 microL was not associated with a further change in TBUT (P = 0.50). Differences between TBUT values measured after using FS and a micropipette calibrated for 1 microL were not significant (P = 0.95). No significant differences were found in the repeatability of TBUT recordings between the instillation techniques used in this study (P = 0.18), although measurement variability increased with mean TBUT for all techniques. With the FS instillation technique described herein, the average volume of fluorescein solution they supplied was less than that delivered by a micropipette set for 1 microL (P = 0.017), but the range of volumes transferred by FS was greater. Values of TBUT are dependent on the volume of fluorescein solution instilled before measurement; thus, attempts should be made to standardize this variable. Accurate estimation of TBUT requires more recordings to be averaged than are normally taken, unless breakup time is very short.


Methoctramine, a selective M2 alpha muscarinic receptor antagonist, does not inhibit carbachol-induced drinking in the rat.
Methoctramine, a selective M2 alpha muscarinic receptor antagonist, was examined for its ability to inhibit carbachol-induced drinking in the rat. Intracerebroventricularly (i.c.v.) administered methoctramine was devoid of activity up to a dose of 100 nmol/rat, whereas higher doses were toxic under our experimental conditions. 4-DAMP, pirenzepine and hexahydrosiladifenidol were also tested. The rank potency order for the compounds (4-DAMP greater than pirenzepine = hexahydrosiladifenidol) was similar to that for their affinity at M1 receptors, as found in experiments in vitro. The putative M1 agonist McN-A-343 was inactive up to doses of 13.9 micrograms/rat. Our data suggest that M2 alpha receptors do not mediate cholinergic drinking in the rat. The question whether M1 or M2 beta muscarinic receptors are involved in this response still awaits a firm answer.


Canine Babesiosis Caused by Large Babesia Species: Global Prevalence and Risk Factors-A Review.
Canine babesiosis is a disease caused by protozoan pathogens belonging to the genus Babesia. Four species of large Babesia cause canine babesiosis (B. canis, B. rossi, B. vogeli, and the informally named B. coco). Although canine babesiosis has a worldwide distribution, different species occur in specific regions: B. rossi in sub-Saharan Africa, B. canis in Europe and Asia, and B. coco in the Eastern Atlantic United States, while B. vogeli occurs in Africa, southern parts of Europe and Asia, northern Australia, southern regions of North America, and in South America. B. vogeli is the most prevalent large Babesia species globally. This results from its wide range of monotropic vector species, the mild or subclinical nature of infections, and likely the longest evolutionary association with dogs. The most important risk factors for infection by large Babesia spp. include living in rural areas, kennels or animal shelters, or regions endemic for the infection, the season of the year (which is associated with increased tick activity), infestation with ticks, and lack of treatment with acaricides.


The effect of ischemic precondition to IL-6 on rat liver ischemia-reperfusion injury in transplantation.
To investigate the effect of ischemic precondition to protect ischemia-reperfusion injury and reduce IL-6 expression in the rats liver transplantation. The rat portal vein infusion of autologous liver transplantation model were used. The rats were divided into ischemic preconditioning rats liver transplantation group (A group), the rats liver transplantation group (B group) and the normal rat control group (C group). Then we analyzed the changes of liver function, liver microstructure and the expression of IL-6, SOD and MDA within 48 h. The pathology of liver in group A showed lobular architecture essentially normal, the liver cells was slightly swell and no significant changes in postoperative 12 h. In transmission electron microscope (46 000×), the mitochondria of liver cells in group A became swelling, elliptical can cristae partially broken. But there still has a small amount of arrangement. While that in group, the mitochondria were swollen, became round, serious visible crest reduce or ruptured. The result of over function test showed that the serum ALT and AST levels in group A and B were both higher than that in group C at each time period, but the serum ALT and AST levels in group A were lower than that in group B. The expression changes of IL-6 in group B were higher than that in group A and B (P<0.05). The expression of MDA in group A is more obvious than that in group B (P<0.05) Ischemic precondition could alleviate part of ischemia-reperfusion injury in the rat liver transplantation, and also could reduce IL-6 expression to protect the liver cells against liver damage and inflammatory cytokine production.


Decision Support Alerts for Medication Ordering in a Computerized Provider Order Entry (CPOE) System: A systematic approach to decrease alerts.
We sought to determine the frequency and type of decision support alerts by location and ordering provider role during Computerized Provider Order Entry (CPOE) medication ordering. Using these data we adjusted the decision support tools to reduce the number of alerts. Retrospective analyses were performed of dose range checks (DRC), drug-drug interaction and drug-allergy alerts from our electronic medical record. During seven sampling periods (each two weeks long) between April 2006 and October 2008 all alerts in these categories were analyzed. Another audit was performed of all DRC alerts by ordering provider role from November 2008 through January 2009. Medication ordering error counts were obtained from a voluntary error reporting system. MEASUREMENTRESULTS: Between April 2006 and October 2008 the percent of medication orders that triggered a dose range alert decreased from 23.9% to 7.4%. The relative risk (RR) for getting an alert was higher at the start of the interventions versus later (RR= 2.40, 95% CI 2.28-2.52; p< 0.0001). The percentage of medication orders that triggered alerts for drug-drug interactions also decreased from 13.5% to 4.8%. The RR for getting a drug interaction alert at the start was 1.63, 95% CI 1.60-1.66; p< 0.0001. Alerts decreased in all clinical areas without an increase in reported medication errors. We reduced the quantity of decision support alerts in CPOE using a systematic approach without an increase in reported medication errors.


New insights into polyurethane biodegradation and realistic prospects for the development of a sustainable waste recycling process.
Polyurethanes are polymeric plastics that were first used as substitutes for traditional polymers suspected to release volatile organic hazardous substances. The limitless conformations and formulations of polyurethanes enabled their use in a wide variety of applications. Because approximately 10 Mt of polyurethanes is produced each year, environmental concern over their considerable contribution to landfill waste accumulation appeared in the 1990s. To date, no recycling processes allow for the efficient reuse of polyurethane waste due to their high resistance to (a)biotic disturbances. To find alternatives to systematic accumulation or incineration of polyurethanes, a bibliographic analysis was performed on major scientific advances in the polyurethane (bio)degradation field to identify opportunities for the development of new technologies to recondition this material. Until polymers exhibiting oxo- or hydro-biodegradative traits are generated, conventional polyurethanes that are known to be only slightly biodegradable are of great concern. The research focused on polyurethane biodegradation highlights recent attempts to reprocess conventional industrial polyurethanes via microbial or enzymatic degradation. This review describes several wonderful opportunities for the establishment of new processes for polyurethane recycling. Meeting these new challenges could lead to the development of sustainable management processes involving polymer recycling or reuse as environmentally safe options for industries. The ability to upgrade polyurethane wastes to chemical compounds with a higher added value would be especially attractive.


Clinical non-superiority of technology-assisted gait training with body weight support in patients with subacute stroke: A meta-analysis.
Technology-assisted gait training (TAGT) with body weight support (BWS) has been designed to provide high numbers of repetitions during stepping practice, but its benefits have been inconclusive. We evaluated the superiority of TAGT over conventional overground training (COT) to judge the clinical benefits. We searched PubMed, Embase and Web of Science databases from their earliest record to July 1, 2019 and included randomized controlled trials of TAGT with BWS, such as robot-assisted gait training and body weight-supported treadmill training, for treating walking disability in patients within 6months after stroke. We conducted a meta-analysis of the outcomes motor impairment, mobility capacity, walking speed, endurance and fitness, balance, and activities of daily living as well as subgroup analyses of initial ambulatory ability and stroke duration. Among 14robotics and 10body weight-supported treadmill studies included for review, 23studies involving 1452participants contributed to the meta-analysis. We found no significant standardized mean differences between TAGT and COT (P>0.05) across all outcome categories in the robotics subgroup, the body weight-supported treadmill subgroup, or both subgroups combined, for both the short and long term. Further subgroup analyses also revealed non-significant standardized mean differences (P>0.05) across all outcomes in the subgroups initially ambulatory, non-ambulatory, or stroke duration less than 3 months. TAGT with BWS was not superior to COT in improving post-stroke recovery in patients with subacute stroke. Strategies other than simply increasing the repetitions by external assistance may be considered to augment the treatment effects of TAGT.


A dot-blot screening procedure for mutated ras oncogenes using synthetic oligodeoxynucleotides.
To analyze human tumors for the presence of mutated ras oncogenes, a procedure was developed based on selective hybridization of mutation-specific oligodeoxynucleotide probes to genomic DNA [Bos et al., Nucl. Acids Res. 12 (1984) 9155-9163]. We have improved this procedure both in sensitivity and speed by including an in vitro amplification step of ras-specific sequences. This amplification step has first been described by Saiki et al. [Science 230 (1985) 1350-1353] and results in a more than 10(4)-fold increase in the sequence which might contain the mutation. Furthermore, we have improved the selectivity of our hybridizations. As a result, mutated ras oncogenes can now be detected with a dot-blot screening procedure requiring less than 1 microgram of tumor DNA.


Does the Synergy Model Implementation Improve the Transition from In-Hospital to Primary Care? The Experience from an Italian Cardiac Surgery Unit, Perspectives, and Future Implications.
The demand for care services in the healthcare system has changed and is triggering a smooth transition from in-hospital to primary care. In this regard, patient-centered-care models of care delivery might provide a framework to follow patients' journeys throughout their transition between different levels of care. Accordingly, an Italian research group at a cardiac hospital in Northern Italy implemented the Synergy Model in a Cardiac Surgery Unit, a patient-centered-care model, and is using the framework of the model to guide a smooth transition of patients towards rehabilitation and primary care after their hospitalization. This discursive paper is focused on the experience, perspectives, and future implications of adopting the Synergy Model to facilitate the transition from in-hospital to primary care. The presented experience and discussion might be helpful to the international debate regarding the strategies to boost a smooth transition from in-hospital to primary care.


Low volume processing of protein blots in rolling drums.
We have evaluated an improved method for processing protein blots on nitrocellulose or nylon membranes using cylindrical plastic containers. The method, which is directly analogous to the commonly used method of photographic processing in rolling drums, uses small values of reagents which are constantly washed over the blotting membrane by rotating the drum horizontally on a roller mixer. Volumes of reagents used are typically less than one-10th of those required for conventional methods using plastic bags or trays. The efficiency of probing and washing steps are greatly improved, giving an all-round increase in sensitivity, ease of processing, and economy of reagents.


Aseptic meningitis and ischemic stroke in relapsing polychondritis.
Relapsing polychondritis (RP) is a rare disease characterized by recurrent inflammation of cartilaginous structures. Its involvement of central nervous system is uncommon. We report the case of a 71-year-old woman whose initial manifestations were RP and meningitis and whose subsequent attack of RP was associated with a left cerebral infarction. The patient responded to steroid therapy in both attacks of RP.


[Attempt to establish genome similarity between Alcaligenes faecalis and several Gram-negative bacteria using the method of molecular hybridization of DNA to DNA].
The technique of DNA-DNA molecular hybridization was used to demonstrate the absence of genome similarity between Alcaligenes faecalis and gram-negative bacteria belonging to the genera Pseudomonas, Enterobacterium, Comamonas producing alkalis, and vibrions. Some similarity in the polynucleotide sequences was found between the DNA of the reper strain of Alcaligenes faecalis 45 (5--10% of homology) and the DNA of the culture belonging to the Achromobacter genus; therefore, the two genera may belong to one and the same family.


Induction of rat alpha 2-macroglobulin in vivo and in hepatocyte primary cultures: synergistic action of glucocorticoids and a Kupffer cell-derived factor.
Turpentine injection into rats elicits enhanced secretion of acute phase proteins including alpha 2-macroglobulin (alpha 2M). Hypophysectomized rats, however, do not respond in this way unless dexamethasone is given together with turpentine. On the other hand, dexamethasone injection alone did not result in an induction of alpha 2M synthesis. When a medium of Kupffer cell cultures was added to hepatocytes, a dose-dependent stimulation of alpha 2M synthesis of up to 4-fold after 10-12 h was observed. However, the presence of low concentrations (10(-9)M) of dexamethasone was essential for the stimulatory effect. We conclude that the acute phase induction of alpha 2M in hepatocytes requires the synergistic action of glucocorticoids and a non-dialysable factor secreted by Kupffer cells.


Determination of small quantities of sulfate (0-12 nmol) in serum, urine, and cartilage of the mouse.
The colorimetric benzidine method of K. S. Dodgson and B. Spencer (1953, Biochem. J. 55, 436-440) for the measurement of inorganic sulfate can be scaled down about 100 times by using disposable 96-well microplates instead of individual cuvettes. Ten-microliter samples of serum and urine, derived from mice, can be analyzed in a simple, rapid, and reliable way without sacrificing the animals. Without prior isolation of sulfated glycosaminoglycans, ester sulfate in mouse patellar cartilage is liberated quantitatively as inorganic sulfate upon acid hydrolysis in 3 M HCl for 16 h at 80 degrees C. To this end the articular cartilage layer of the patella must be separated in toto from the underlying bone. Subsequent hydrolysis in polypropylene tubes gives accurate results. In contrast, hydrolysis in borosilicate glass vials is useless, since nanomoles of sulfate added cannot be recovered adequately. The thin patellar cartilage layer obtained from 10-week-old male mice contains about 5 nmol of sulfate, an amount easily measured with the developed microplate benzidine method.


A method for the specific detection of resident bacteria in brine shrimp larvae.
In this study, we describe an easy but efficient method to specifically target the intestinal resident microbiota in brine shrimp larvae during DGGE analysis, hereby excluding the interference of both transient (luminal) bacteria and body surface bacteria. This effective technique has several advantages over alternative methods, with respect of ease of use and rapidity.


Determination of residual antiplatelet activity of clopidogrel before neuraxial injections.
Guidelines recommend discontinuation of clopidogrel for 7 days before a neuraxial injection, while other directives suggest that 5 days might be adequate. We examined the time course of antiplatelet activity after clopidogrel discontinuation in patients undergoing epidural injections. Thirteen patients were studied at baseline, 3, 5, and 7 days after discontinuation of clopidogrel. P(2)Y(12) determinations were performed using the VerifyNow(®) assay (Accumetrics, San Diego, CA, USA), and clot closure times with stimulation by collagen/epinephrine and collagen/adenosine diphosphate using the PFA-100(®) (Platelet Function Analyzer, Siemens Diagnostics, Deerfield, IL, USA). Repeated-measures ANOVA was used to evaluate P(2)Y(12) platelet reaction units, PFA-100 closure times, and per cent P(2)Y(12) inhibition values. Wilcoxon's signed-rank test was used to compare the frequencies of ≥30%, 11-29%, and ≤10% platelet inhibition between the baseline and subsequent sampling points after discontinuation of clopidogrel. On day 3 after clopidogrel discontinuation, two subjects had ≥30%, seven subjects had 11-29%, and four subjects had ≤10% platelet inhibition; the corresponding numbers were 0, 3, and 10 subjects on day 5 (P=0.04). There were no differences between the ≥30%, 11-29%, and <10% platelet inhibition groups between days 5 and 7 (0, 0, and 13 subjects, P=1.0). PFA-ADP closure times were normal throughout the study period except in one patient. These findings support the recommendation that discontinuation of clopidogrel for 5 days allows >70% of platelet function and might be adequate before a neuraxial injection is performed.


Comparative study on concentrations of deoxynivalenol and zearalenone in kernels of transgenic Bt maize hybrids and nontransgenic maize hybrids.
Ears from seven pairs of Bt maize hybrids / isogenic maize hybrids from field experiments in the year 1999 were collected arbitrarily and divided into corn borer (ECB) infested and not infested ears, respectively. The kernels were analysed for the mycotoxins deoxynivalenol (DON) and zearalenone (ZON).The percentage of infested ears was significantly lower in case of Bt maize (5%) as compared with non transgenic maize (31%). The study demonstrated further that the DON concentration in kernels of ECB infested ears of the non Bt maize hybrids was significantly higher than the DON concentration of the other groups. In the case of zearalenone, the same trend was observed. When the mean concentrations of the Bt and non-Bt hybrids, respectively, are considered, the lower contamination of Bt maize hybrids with DON and ZON, compared with their isogenic counterparts, is even more evident.


Extracellular vesicles from human umbilical cord mesenchymal stem cells prevent steroid-induced avascular necrosis of the femoral head via the PI3K/AKT pathway.
Extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stem cells (hucMSC) have excellent therapeutic potential for many diseases. The aim of this study was to define the role of hucMSC-EVs in the prevention and treatment of steroid-induced avascular necrosis of the femoral head (SANFH). After establishing the SANFH rat model, the effects of hucMSC-EVs were assessed by measuring the microstructure of the femoral head using HE staining, micro-computed tomography (micro-CT), and TUNEL staining. The administration of hucMSC-EVs caused a significant reduction to glucocorticoids (GCs)-induced osteoblast apoptosis and empty lacuna of the femoral head, while effectively improving the microstructure. HucMSC-EVs rescued the deactivation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway induced by GCs, and reversed the proliferation and migration of osteoblasts inhibited by GCs. In addition, hucMSC-EVs attenuated the inhibitory effects of GCs on rat osteoblast osteogenesis, angiogenesis of endothelial cells, and prevented osteoblast apoptosis. However, the promoting effects of hucMSC-EVs were abolished following the blockade of PI3K/AKT on osteoblasts. hucMSC-EVs were found to prevent glucocorticoid-induced femoral head necrosis in rats through the PI3K/AKT pathway.


Association of interleukin-12B gene polymorphisms and mRNA expression with preeclampsia.
To explore the effects of functional genetic polymorphisms of the interleukin-12B (IL-12B) gene on the susceptibility to preeclampsia in northern Chinese women. Maternal peripheral blood from 306 preeclamptic women and 310 control women and the placentas from 52 preeclamptic and 55 control women were collected. Two polymorphisms (rs17860508 and rs3212227) of the IL-12B gene were genotyped by polymerase chain reaction (PCR) with a direct sequencing method. The mRNA expression of IL-12B in the placentas was measured by quantitative real-time PCR (qRT-PCR). Significant differences were observed between preeclamptic women and the control group in the genotype frequencies of rs17860508 (P = 0.017). Compared with the TTAGAG/TTAGAG genotype of rs17860508, the GC/GC genotype were associated with a higher risk of preeclampsia (adjusted OR: 1.95; 95% CI = 1.18-3.22; P = 0.009), especially the early-onset preeclampsia (adjusted OR: 2.40; 95% CI = 1.23-4.68; P = 0.010). The qRT-PCR results showed that the mRNA levels of IL-12B were significantly higher in the placentas of preeclampsia patients than that in the placentas of controls (P = 0.001). Moreover, the expression of IL-12B mRNA was significantly higher in the placentas of patients carrying the GC/GC genotype than in those carrying the TTAGAG/GC (P = 0.007) and TTAGAG/TTAGAG (P = 0.005) genotypes. The GC/GC genotype of rs17860508 polymorphism may be a risk factor for the early-onset preeclampsia by upregulating the expression of IL-12B in northern Chinese women.


Potential role of IL-37 in atherosclerosis.
IL-37 is a member of the IL-1 family, but unlike most other members of this family of cytokines, it has wide-ranging anti-inflammatory properties. Initially shown to bind IL-18 binding protein and prevent IL-18-mediated inflammation, its known role has been expanded to include distinct pathways, both intracellular involving the transcription factor Smad3, and extracellular via binding to the orphan receptor IL-1R8. A number of recent publications investigating the role of IL-37 in atherosclerosis and ischemic heart disease have revealed promising therapeutic value of the cytokine. Although research concerning the role of IL-37 and its mechanism in atherosclerosis is relatively scant, there are a number of well-known atherosclerotic processes that this cytokine can mediate with the potential of modulating the disease progression itself. This review will probe in detail the effects of IL-37 on important pathological processes such as inflammation, dysregulated lipid metabolism, and apoptosis, by analyzing existing data as well as exploring the potential of this cytokine to influence these properties.


An unnatural base pair for incorporating amino acid analogs into proteins.
An unnatural base pair of 2-amino-6-(2-thienyl)purine (denoted by s) and pyridin-2-one (denoted by y) was developed to expand the genetic code. The ribonucleoside triphosphate of y was site-specifically incorporated into RNA, opposite s in a template, by T7 RNA polymerase. This transcription was coupled with translation in an Escherichia coli cell-free system. The yAG codon in the transcribed ras mRNA was recognized by the CUs anticodon of a yeast tyrosine transfer RNA (tRNA) variant, which had been enzymatically aminoacylated with an unnatural amino acid, 3-chlorotyrosine. Site-specific incorporation of 3-chlorotyrosine into the Ras protein was demonstrated by liquid chromatography-mass spectrometry (LC-MS) analysis of the products. This coupled transcription-translation system will permit the efficient synthesis of proteins with a tyrosine analog at the desired position.


Moth wings are acoustic metamaterials.
Metamaterials assemble multiple subwavelength elements to create structures with extraordinary physical properties (1-4). Optical metamaterials are rare in nature and no natural acoustic metamaterials are known. Here, we reveal that the intricate scale layer on moth wings forms a metamaterial ultrasound absorber (peak absorption = 72% of sound intensity at 78 kHz) that is 111 times thinner than the longest absorbed wavelength. Individual scales act as resonant (5) unit cells that are linked via a shared wing membrane to form this metamaterial, and collectively they generate hard-to-attain broadband deep-subwavelength absorption. Their collective absorption exceeds the sum of their individual contributions. This sound absorber provides moth wings with acoustic camouflage (6) against echolocating bats. It combines broadband absorption of all frequencies used by bats with light and ultrathin structures that meet aerodynamic constraints on wing weight and thickness. The morphological implementation seen in this evolved acoustic metamaterial reveals enticing ways to design high-performance noise mitigation devices.


Ultrasound detection of focal bacterial nephritis (lobar nephronia) and its evolution into a renal abscess.
A case of acute focal bacterial nephritis (lobar nephronia) which evolved into a renal abscess is reported. This case is unusual for 2 reasons: the focal nephritis was isoechoic (not previously reported), and it progressed to an abscess despite antibiotic therapy. Ultrasound initially detected the focal nephritis and later confirmed its progression to an abscess. Successful treatment was obtained with sonographically guided percutaneous catheter drainage in conjunction with systemic antibiotics.


Associations of handedness with hair color and learning disabilities.
Forms containing the Edinburgh handedness inventory and questions about learning disabilities, hair color, self-described handedness, age, gender, parental handedness and twinning were received from 1117 randomly selected professionals. Laterality scores (LS, range -100 to +100) were calculated for each respondent based on the handedness inventory and were correlated with the above variables. Among blonds, the frequency of non right-handedness (NRH, LS less than or equal to 70) was 44% compared to 24% of non-blonds (chi 2 = 23.5, P less than 0.0001). Learning disabilities (LD) were present in 9% of NRH (LS less than or equal to 70) as against 3% of those with LS greater than 70 (chi 2 = 22.1, P less than 0.0001). Associations between LS and self-described handedness, parental handedness, gender, and age are also presented. Possible explanations for the association of hair color and handedness are discussed in light of recent data on altered visual system pathways in albinos. Problems in the measurement of handedness are discussed.


Neurobiology: New connections between integrins and axon guidance.
Axon guidance molecules such as netrins, semaphorins, Slits and ephrins provide the cues required for accurate patterning of axonal projections in the nervous system. Recent reports have described multiple paradigms by which these molecules interact with integrin adhesion receptors in and outside the neuronal tissues.


The association of low birthweight and prematurity on outcomes in children and adults with nephrotic syndrome-a NEPTUNE cohort study.
In single-center studies, both preterm birth and low birth weight (LBW) are associated with worse outcomes in childhood nephrotic syndrome. Using the Nephrotic Syndrome Study Network (NEPTUNE) observational cohort, we tested the hypothesis that in patients with nephrotic syndrome, hypertension, proteinuria status, and disease progression would be more prevalent and more severe in subjects with LBW and prematurity singly or in combination (LBW/prematurity). Three hundred fifty-nine adults and children with focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) and available birth history were included. Estimated glomerular filtration rate (eGFR) decline and remission status were primary outcomes, and secondary outcomes were kidney histopathology, kidney gene expression, and urinary biomarkers. Logistic regression was used to identify associations with LBW/prematurity and these outcomes. We did not find an association between LBW/prematurity and remission of proteinuria. However, LBW/prematurity was associated with greater decline in eGFR. This decline in eGFR was partially explained by the association of LBW/prematurity with APOL1 high-risk alleles, but the association remained after adjustment. There were no differences in kidney histopathology or gene expression in the LBW/prematurity group compared to normal birth weight/term birth. LBW and premature babies who develop nephrotic syndrome have a more rapid decline in kidney function. We did not identify clinical or laboratory features that distinguished the groups. Additional studies in larger groups are needed to fully ascertain the effects of (LBW) and prematurity alone or in combination on kidney function in the setting of nephrotic syndrome.


Competition and coexistence with multiple life-history stages.
Do complex life histories affect the conditions under which competitors can coexist? We investigated this using a two-species, two-stage Ricker model. With complex life cycles, the competition coefficients associated with each life-history stage suggest one of three competitive outcomes-coexistence, alternate stable states, or competitive exclusion-that depend on the relative magnitudes of intraspecific and interspecific competition. When the two stages suggest the same outcome, only that outcome can occur. When the stages suggest different outcomes, either one may prevail. It is also possible to have emergent outcomes, in which the outcome is not suggested by either stage. This can occur when the two stages suggest competitive exclusion by opposite species or when one stage suggests alternate stable states and the other suggests coexistence. Therefore, determining the mechanisms of coexistence in species with complex life histories may require consideration of competitive interactions within all life-history stages.