Asynchronous nuclear cycles in multinucleated Plasmodium falciparum facilitate rapid proliferation.
Malaria-causing parasites proliferate within erythrocytes through schizogony, forming multinucleated stages before cellularization. Nuclear multiplication does not follow a strict geometric 2n progression, and each proliferative cycle produces a variable number of progeny. Here, by tracking nuclei and DNA replication, we show that individual nuclei replicate their DNA at different times, despite residing in a shared cytoplasm. Extrapolating from experimental data using mathematical modeling, we provide strong indication that a limiting factor exists, which slows down the nuclear multiplication rate. Consistent with this prediction, our data show that temporally overlapping DNA replication events were significantly slower than partially overlapping or nonoverlapping events. Our findings suggest the existence of evolutionary pressure that selects for asynchronous DNA replication, balancing available resources with rapid pathogen proliferation.


Efficacy and Safety of Paclitaxel-Coated Balloon for the Treatment of In-Stent Restenosis in High-Risk Patients.
In-stent restenosis (ISR) is a major cause of failure of percutaneous coronary intervention. The efficacy and safety of drug-coated balloon (DCB) in patients with high-risk clinical features are largely unknown. We enrolled 82 consecutive patients at high risk of bleeding with angiographically significant (diameter stenosis ≥ 50%) ISR of bare metal stent (BMS) or drug-eluting stent (DES), treated with paclitaxel-coated balloon. All patients presented at least one of the following criteria: high bleeding risk, neoplasm, chronic inflammatory disease, and need for noncardiac surgery. Dual antiplatelet therapy was indicated for 4 weeks after the procedure. At angiographic follow-up, overall late lumen loss was 0.24 ± 0.32 mm, with no significant difference between BMS-ISR and DES-ISR (0.25 ± 0.35 vs 0.22 ± 0.30 mm, p = 0.714). The Kaplan-Meier estimate for major adverse clinical events-free survival at 3 years was 81.4% (82.3% in BMS-ISR vs 79.4% in DES-ISR, log-rank p = 0.866). No stent thrombosis has been recorded. In conclusion, the use of paclitaxel-coated balloon seems to be associated with favorable outcomes after percutaneous coronary intervention for BMS-ISR or DES-ISR in patients with high-risk clinical features and could be considered as a reasonable option in the presence of systemic co-morbidities and contraindications to long-term dual antiplatelet therapy.


In vitro ruminal fermentation and cow-to-mouse fecal transplantations verify the inter-relationship of microbiome and metabolome biomarkers: potential to promote health in dairy cows.
There are differences in the gut microbiome and metabolome when the host undergoes different physical or pathological conditions. However, the inter-relationship of microbiome and metabolome biomarkers to potentially promote the health of dairy cows needs to be studied. Further, the development of next-generation probiotics for dairy cattle health promotion has not been demonstrated. In the present study, we identified the microbiome and metabolome biomarkers associated with healthy cows. We analyzed the relationships of the ruminal microorganism profile and metabolites between healthy and mastitis lactating dairy cows. The roles of bacterial biomarker were further verified by in vitro fermentation and cow-to-mouse fecal microbiota transplantation (FMT). Two species, Ruminococcus flavefaciens and Bifidobacterium longum subsp. longum, and six rumen metabolites were positively correlated with healthy cows by Spearman's correlation analysis. Through in vitro ruminal fermentation, inoculating R. flavefaciens and B. longum subsp. longum showed the upregulation of the levels of putrescine, xanthurenic acid, and pyridoxal in the mastitis ruminal fluid, which confirmed the inter-relationships between these microbiota and metabolites associated with healthy cows. Further, we verified the role of R. flavefaciens and B. longum subsp. longum in promoting health by FMT. The administration of R. flavefaciens and B. longum subsp. longum reduced the death rate and recovered the bodyweight loss of germ-free mice caused by FMT mastitis feces. We provided evidence that the bacterial biomarkers alter downstream metabolites. This could indirectly indicate that the two bacterial biomarkers have the potential to be used as next-generation probiotics for dairy cattle, although it needs more evidence to support our hypothesis. Two species, R. flavefaciens and B. longum subsp. longum, with three metabolites, putrescine, xanthurenic acid, and pyridoxal, identified in the ruminal fluid, may point to a new health-promoting and disease-preventing approach for dairy cattle.


Comparative transcriptome sequencing of tolerant rice introgression line and its parents in response to drought stress.
Rice (Oryza sativa. L) is more sensitive to drought stress than other cereals, and large genotypic variation in drought tolerance (DT) exists within the cultivated rice gene pool and its wild relatives. Selective introgression of DT donor segments into a drought-sensitive (DS) elite recurrent parent by backcrossing is an effective way to improve drought stress tolerance in rice. To dissect the molecular mechanisms underlying DT in rice, deep transcriptome sequencing was used to investigate transcriptome differences among a DT introgression line H471, the DT donor P28, and the drought-sensitive, recurrent parent HHZ under drought stress. The results revealed constitutively differential gene expression before stress and distinct global transcriptome reprogramming among the three genotypes under a time series of drought stress, consistent with their different genotypes and DT phenotypes. A set of genes with higher basal expression in both H471 and P28 compared with HHZ were functionally enriched in oxidoreductase and lyase activities, implying their positive role in intrinsic DT. Gene Ontology analysis indicated that common up-regulated genes in all three genotypes under mild drought stress were enriched in signaling transduction and transcription regulation. Meanwhile, diverse functional categories were characterized for the commonly drought-induced genes in response to severe drought stress. Further comparative transcriptome analysis between H471 and HHZ under drought stress found that introgression caused wide-range gene expression changes; most of the differentially expressed genes (DEGs) in H471 relative to HHZ under drought were beyond the identified introgressed regions, implying that introgression resulted in novel changes in expression. Co-expression analysis of these DEGs represented a complex regulatory network, including the jasmonic acid and gibberellin pathway, involved in drought stress tolerance in H471. Comprehensive gene expression profiles revealed that genotype-specific drought induced genes and genes with higher expression in the DT genotype under normal and drought conditions contribute jointly to DT improvement. The molecular genetic pathways of drought stress tolerance uncovered in this study, as well as the DEGs co-localized with DT-related QTLs and introgressed intervals, will serve as useful resources for further functional dissection of the molecular mechanisms of drought stress response in rice.


Dietary and nutritional indications in hepatic encephalopathy.
The restriction of dietary protein has long been considered a main stay in the therapy of hepatic encephalopathy. More recently it has been recognized that protein energy malnutrition is frequent in advanced liver disease and may adversely affect the patients'outcome. Moreover studies on inter-organ ammonia exchange in liver cirrhosis have shown that the muscle may have a crucial role in ammonia detoxification. In light of these evidences nutritional guidelines have proposed that protein restriction should be avoided in patients with hepatic encephalopathy as protein requirement is even increased in cirrhotic patients. Survey about the current clinical practice show that protein restriction is still considered advisable in patients with hepatic encephalopathy, however a recent trial evidenced that a low protein diet in patients hospitalized for acute hepatic encephalopathy exacerbates protein breakdown without inducing any specific clinical benefit when compared to a normal protein regimen. The relevance of an adequate protein intake and possible strategies to implement protein tolerance are also discussed.


In vivo imaging of dendritic spines during electrographic seizures.
Epilepsy is associated with significant neurological morbidity, including learning disabilities, motor deficits, and behavioral problems. Although the causes of neurological dysfunction in epilepsy are multifactorial, accumulating evidence indicates that seizures in themselves may directly cause brain injury. Although it is clear that seizures can result in neuronal death, it is likely that under some circumstances seizures can induce more subtle functional or structural alterations in neurons. We induced focal neocortical seizures with 4-aminopyridine in transgenic mice expressing green fluorescent protein in cortical neurons and sequentially imaged individual dendrites in living animals with two-photon laser-scanning microscopy to determine whether these seizures caused acute alterations in dendritic spine morphology. No dendritic alterations were observed in anesthetized animals during electrographic seizures over a 3-hour period. Similarly, in unanesthetized mice, low-stage, clinical electrographic seizures had minimal effect on dendritic spines. More severe, high-stage seizures in unanesthetized mice were associated with a moderate loss of spines and dendritic swelling, but this effect may have been contingent on a synergistic action of phototoxicity from the imaging method itself. Overall, our results suggest that most neocortical seizures have minimal acute effects on dendrites over several hours, but may predispose to dendritic injury under extreme conditions.


Ionizing radiation induces EphA2 S897 phosphorylation in a MEK/ERK/RSK-dependent manner.
The EphA2 tyrosine kinase is frequently overexpressed in human tumors that are also treated with radiation. However, few studies have examined the effect of radiation on the EphA2 receptor itself. The purpose of this project was to investigate the impact of radiation on EphA2 to better understand mechanisms of radioresistance. Cell lines were exposed to X-rays and assayed for changes in EphA2 protein levels and phosphorylation over time by Western blotting. HEK293 cells stably expressing wild-type EphA2 or the S897A mutant were analyzed for cell survival from X-rays. Treatment of different cancer cell lines with 2 Gy of X-rays induced the phosphorylation of EphA2 on S897 but no changes were found in EphA2 total levels or its tyrosine phosphorylation. Radiation-induced S897 phosphorylation was unaffected by an AKT inhibitor but blocked by a MEK or RSK inhibitor. HEK293 cells expressing the EphA2 S897A mutant had a nearly 2-fold lower level of cell survival from X-rays than cells expressing wild-type EphA2. These findings show that radiation induces S897 EphA2 phosphorylation, an event associated with increased cell survival. Therefore, targeting pathways that mediate EphA2 S897 phosphorylation may be a beneficial strategy to reduce radioresistance.


Dietary Probiotic Supplementation Suppresses Subclinical Necrotic Enteritis in Broiler Chickens in a Microbiota-Dependent Manner.
Chicken meat is one of the most consumed meats worldwide and poultry production is increasing at an exponential rate. Reducing antibiotic usage has resulted in the recurrence of subclinical necrotic enteritis again and influenced global poultry production. Probiotics are potential antibiotic substitutes that can be used to prevent subclinical necrotic enteriti. However, the precise mechanism of action of probiotics and information on which gut microbes confer this efficacy remain elusive. The subclinical necrotic enteritis animal model was used to reveal the mechanism underlying the effect of probiotics on intestinal health through RNA sequencing and 16S rDNA amplicon sequencing. Bacillus licheniformis H2 feeding significantly reduced the relative abundance of Clostridium perfringens in the ileum and markedly ameliorated the pathological damage in the ileum and liver. In addition, oral administration of B. licheniformis H2 contributed to the enhancement of the intestinal barrier function and epithelial renewal, reducing energy consumption, and improving enteral nutrition absorption. Probiotic B. licheniformis H2 also ameliorated the inflammatory response and increased the immunity of subclinical necrotic enteritis infected broilers. Finally, B. licheniformis H2 feeding regulated liver gene expression to suppress immune response and promoted growth and metabolism depending on the gut microbiota. These results indicated the mechanism of probiotic action of B. licheniformis H2 in maintaining intestinal health and thus promoting growth and B. licheniformis H2 may serve as an antibiotic substitute to prevent subclinical necrotic enteritis in poultry farming.


Synthesis and Stability of Ammonium Selenocyanate [NH4][SeCN] and Its Reactivity toward Ag[SeCN].
[NH4][SeCN] and Ag[SeCN] were synthesized by salt metathesis starting from the respective chlorides and K[SeCN]. Both products were fully characterized by single-crystal and powder X-ray diffraction, differential scanning calorimetry-thermogravimetric analysis (DSC-TGA), and solid-state IR and Raman spectroscopy. Quantum-mechanical calculations allowed for detailed assignment and interpretation of vibrational spectra. For dissolved [NH4][SeCN], nuclear magnetic resonance spectra were collected. High-temperature powder X-ray diffraction (HT-PXRD) allowed for the analysis of the thermal behavior of solid [NH4][SeCN]. Furthermore, the reaction of [NH4][SeCN] with Ag[SeCN] leads to the formation of the ternary salts [NH4][Ag(SeCN)2] and [NH4]3[Ag(SeCN)4]. The structures of the latter were determined from single-crystal X-ray diffraction (SC-XRD) data, and bulk analysis was performed by Rietveld refinement, Raman spectroscopy, and elemental analysis.


Metabolic regulation of the lysosomal cofactor bis(monoacylglycero)phosphate in mice.
Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid, is a phospholipid that promotes lipid sorting in late endosomes/lysosomes by activating lipid hydrolases and lipid transfer proteins. Changes in the cellular BMP content therefore reflect an altered metabolic activity of the endolysosomal system. Surprisingly, little is known about the physiological regulation of BMP. In this study, we investigated the effects of nutritional and metabolic factors on BMP profiles of whole tissues and parenchymal and nonparenchymal cells. Tissue samples were obtained from fed, fasted, 2 h refed, and insulin-treated mice, as well as from mice housed at 5°C, 22°C, or 30°C. These tissues exhibited distinct BMP profiles that were regulated by the nutritional state in a tissue-specific manner. Insulin treatment was not sufficient to mimic refeeding-induced changes in tissue BMP levels, indicating that BMP metabolism is regulated by other hormonal or nutritional factors. Tissue fractionation experiments revealed that fasting drastically elevates BMP levels in hepatocytes and pancreatic cells. Furthermore, we observed that the BMP content in brown adipose tissue strongly depends on housing temperatures. In conclusion, our observations suggest that BMP concentrations adapt to the metabolic state in a tissue- and cell-type-specific manner in mice. Drastic changes observed in hepatocytes, pancreatic cells, and brown adipocytes suggest that BMP plays a role in the functional adaption to nutrient starvation and ambient temperature.


Association between long-term use of prolactin-elevating antipsychotics in women and the risk of breast cancer: What are the clinical implications?
Some antipsychotic drugs elevate prolactin, and hyperprolactinaemia is associated with an increased risk of breast cancer. Women with schizophrenia have an increased incidence of breast cancer, but also multiple risk factors for the condition. This paper will critically review recent epidemiological studies concerning antipsychotics and breast cancer from a psychiatric perspective. Two recent epidemiological studies have found an association between use of prolactin-elevating antipsychotics and breast cancer in women with schizophrenia and other psychotic disorders. Prolactin-elevating drugs include paliperidone, risperidone, amisulpride and haloperidol, whilst prolactin-sparing antipsychotics included aripiprazole, brexpiprazole, cariprazine and quetiapine. In the two studies, estimated increased risks of breast cancer were disconcertingly high (up to 62%), but a third recent study found only a weak dose-response association. There are extensive methodological complications in this research, including the extent to which studies measure other risk factors for breast cancer and disagreement about the extent of prolactin elevation by some antipsychotics. Although causation between prolactin elevating antipsychotics and breast cancer in women has not been demonstrated, recent epidemiological reports are worrying. For women on antipsychotics, informed consent should ideally include discussion of breast cancer concerns within the wider context of treatment benefits and risks.


Low-Charge Electrotherapy in Geriatric Major Depressive Disorder Patients: A Case Series.
To examine the feasibility of low-charge electrotherapy (LCE) in treating geriatric major depressive disorder (MDD) patients. Bi-temporal LCEs (approximately 25 mC) were performed with an electroconvulsive therapy (ECT) instrument three times per week. We used the Hamilton Depression Scale 17 (HAMD-17) and the Hamilton Anxiety Scale (HAMA) to assess the effects of LCE and the Mini-Mental State Examination (MMSE) to evaluate the cognitive function change before and after LCE. Six visits occurred at the baseline, after LCE sessions 3, 6, and 9, after the last session, and at the end of the one-month follow-up period. Four patients were enrolled in the study. Two patients completed all LCE sessions. Two patients withdrew during the trial, one due to the adverse event of uroschesis potentially caused by atropine and the other due to her own will. All four patients completed the follow-up sessions. The HAMD-17 and HAMA scores were reduced significantly at the last LCE session and the end of the follow-up period compared with the scores at the baseline. As measured by the MMSE, cognitive impairment showed no significant changes at the last LCE session and the end of the follow-up period compared with that at the baseline. In this case series, LCE showed potential as an alternative current-based treatment for treating geriatric MDD patients. Further research is needed to assess the efficiency and safety of LCE.


Detection of endo-epicardial atrial low-voltage areas using unipolar and omnipolar voltage mapping.
Background: Low-voltage areas (LVA) can be located exclusively at either the endocardium or epicardium. This has only been demonstrated for bipolar voltages, but the value of unipolar and omnipolar voltages recorded from either the endocardium and epicardium in predicting LVAs at the opposite layer remains unknown. The goal of this study was therefore to compare simultaneously recorded endo-epicardial unipolar and omnipolar potentials and to determine whether their voltage characteristics are predictive for opposite LVAs. Methods: Intra-operative simultaneous endo-epicardial mapping (256 electrodes, interelectrode distances 2 mm) was performed during sinus rhythm at the right atrium in 93 patients (67 ± 9 years, 73 male). Cliques of four electrodes (2 × 2 mm) were used to define maximal omnipolar (Vomni,max) and unipolar (Vuni,max) voltages. LVAs were defined as Vomni,max ≤0.5 mV or Vuni,max ≤1.0 mV. Results: The majority of both unipolar and omnipolar LVAs were located at only the endocardium (74.2% and 82.0% respectively) or epicardium (52.7% and 47.6% respectively). Of the endocardial unipolar LVAs, 25.8% were also located at the opposite layer and 47.3% vice-versa. In omnipolar LVAs, 18.0% of the endocardial LVAs were also located at the epicardium and 52.4% vice-versa. The combination of epicardial Vuni,max and Vomni,max was most accurate in identifying dual-layer LVAs (50.4%). Conclusion: Unipolar and omnipolar LVAs are frequently located exclusively at either the endocardium or epicardium. Endo-epicardial LVAs are most accurately identified using combined epicardial unipolar and omnipolar voltages. Therefore, a combined endo-epicardial unipolar and omnipolar mapping approach is favoured as it may be more indicative of possible arrhythmogenic substrates.


Forked end: a novel transmembrane protein involved in neuromuscular specificity in drosophila identified by gain-of-function screening.
The Drosophila neuromuscular connectivity provides an excellent model system for studies on target recognition and selective synapse formation. To identify molecules involved in neuromuscular recognition, we conducted gain-of-function screening for genes whose forced expression in all muscles alters the target specificity. We report here the identification of a novel transmembrane protein, Forked end (FEND), encoded by the fend gene, by the said screening. When the FEND expression was induced in all muscles, motoneurons that normally innervate muscle 12 formed ectopic synapses on a neighboring muscle 13. The target specificity of these motoneurons was also altered in the loss-of-function mutant of fend. During embryonic development, fend mRNA was detected in a subset of cells in the central nervous system and in the periphery. These results suggest that FEND is a novel axon guidance molecule involved in neuromuscular specificity.


Active form of dipteran-specific insecticidal protein cryllA produced by Bacillus thuringiensis subsp. israelensis.
The nucleotide sequence of the cry11A gene from Bacillus thuringiensis subsp. israelensis strain HD522 was analyzed and the molecular characterization of CryllA toxin was done. The 70-kDa CryllA protoxin was processed in vitro into 36- and 32-kDa fragments by trypsin and into 34- and 32-kDa fragments by gut proteases from C. pipiens. These two processed fragments are associated together to form the heterodimer. The results of the binding assay with BBMV and the bioassay toward C. pipiens larvae suggested that the heterodimer was biologically as active as the non-digested CryllA toxin and the intramolecular cleavage did not promote the insecticidal activity. These results suggested that a probable complex of the 36- or 34-kDa and 32-kDa fragments was also one of the possible active forms of Cry11A, and that the biological functions of CryllA was not essentially affected by the intramolecular cleavage of the 70-kDa protein.


Trypanosoma madeirae sp. n.: A species of the clade T. cruzi associated with the neotropical common vampire bat Desmodus rotundus.
Molecular phylogenetic studies have revealed the growing diversity of bat trypanosomes. Here, 14 isolates from blood samples of the vampire bat Desmodus rotundus (Phyllostomidae) from Rio de Janeiro, Southeast Brazil, were cultivated, and morphologically and molecularly characterized. All isolates represent a novel species named Trypanosoma madeirae n. sp. positioned in the Neobat lineage of the clade T. cruzi. The Neobat lineage also comprises closely related trypanosomes of clades Neotropic 1, 2 and 3 from diverse phyllostomid species. Trypanosomes of Neotropic 1, found in Trachops cirrhosus and Artibeus jamaicensis (phyllostomids), likely represent a different species or genotype closely related to T. madeirae. Consistent with its phylogenetic positioning, T. madeirae differs from Trypanosoma cruzi in morphology of both epimastigote and trypomastigote culture forms and does not infect Triatoma infestans. Similar to its closest relatives of Neobat lineage, T. madeirae was unable to develop within mammalian cells. To date, PCR-surveys on archived blood/liver samples unveiled T. madeirae exclusively in D. rotundus from Southern to Northern Brazil. The description of a new species of bat trypanosome associated with vampire bats increases the repertoire of trypanosomes infecting D. rotundus, currently comprised of Trypanosoma cruzi, T. cruzi marinkellei, Trypanosoma dionisii, Trypanosoma rangeli, Trypanosoma pessoai, and Trypanosoma madeirae.


Persistence of biologic activity after disappearance of propranolol from the serum.
In order to evaluate the duration of the biologic effects of propranolol after the drug was discontinued, we evaluated a variety of noninvasively determined hemodynamic parameters. Significant depression was found in the heart rate (18 per cent), cardiac output (13 per cent) (determined echocardiographically), and the triple product of blood pressure, heart rate, and systolic ejection time (16 per per cent) during administration or propranolol (200 mg. per day) to 9 normal volunteers. Significant depression of these parameters was present 12 hours after discontinuing the drug. By 12 hours, serum propranolol levels had returned 90 per cent toward their base line; however, at the same time, the heart rate and cardiac output had returned only 19.4 and 14.3 per cent toward their base-line values, and the triple product had returned 41 per cent toward its baseline. By 36 hours no biologic effect was seen. Thus if propranolol were discontinued 2 days prior to cardiac surgery, no significant biologic effect would remain to complicate the patient's postoperative course.


Comparing the Effects of 2D and 3D Imaging Systems on Laparoscopic Pyeloplasty Outcomes in the Treatment of Adult Ureteropelvic Junction Obstruction.
Background: The aim of this study was to compare the efficacy, safety, and the clinical and perioperative outcomes of two-dimensional (2D) and three-dimensional (3D) laparoscopic imaging systems in adult patients undergoing laparoscopic pyeloplasty in our clinics due to ureteropelvic junction (UPJ) obstruction. Methods: A total of 46 adult patients who had undergone laparoscopic pyeloplasty due to UPJ obstruction were included in the study. Cases that had undergone the operation before January 2019 were retrospectively evaluated with the 2D imaging systems. Cases after that date were evaluated by using the 3D imaging systems, and the operative, perioperative, and postoperative findings of these patients were recorded prospectively. Patients who had undergone laparoscopic pyeloplasty were classified into two groups as the "2D group" and the "3D group." To standardize the preoperative findings, the cases that were operated by a single surgeon experienced in both 2D and 3D imaging systems were included in the study. The demographic characteristics and the clinical findings of the patients were compared between the groups. Results: A total of 41 patients were included in the study. The mean age was 27.7 ± 9.17 years. Among the patients, 23 (56.1%) were in the 2D group and 18 (43.9%) were in the 3D group. No statistically significant difference was observed between groups with regard to the demographic characteristics of the patients. According to the perioperative and postoperative findings of the patients, the duration of the operation was significantly shorter in the 3D group. Conclusion: The duration of the operation was significantly reduced in the 3D image-guided laparoscopic pyeloplasty in the treatment of UPJ obstruction of the adult, compared with 2D image-guided operations. The 3D imaging systems provide a better image quality, an important convenience in intraoperative saturation, and low rates of complication in laparoscopic pyeloplasty, and they may be used safely and effectively.


High Expression of ABRACL Is Associated with Tumorigenesis and Affects Clinical Outcome in Gastric Cancer.
The ABRA C-terminal like (ABRACL) protein belongs to a novel family of low-molecular weight proteins that increase actin dynamics and cell motility. It is involved in various diseases including cancer; however, its role in gastric cancer is unclear. In this study, the expression of ABRACL in gastric cancer and its relationships with patients' clinicopathological features and survival are examined. Sample expression profiles were downloaded from the Gene Expression Omnibus database and the Cancer Genome Atlas. ABRACL expression at the protein level in normal gastric and gastric cancer tissues was compared by using immunohistochemistry staining data provided by the Human Protein Atlas. Correlations between ABRACL expression and clinicopathological features are analyzed by chi-square tests. Patient survival was evaluated by Kaplan-Meier analysis. ABRACL expression is upregulated in gastric cancer tissues than in normal tissues. High ABRACL levels indicated a poor prognosis. ABRACL expression (low ABRACL, n = 96; high ABRACL, n = 96) in gastric cancer tissues (primary data from GSE15459) is significantly correlated with poor overall survival (χ2 = 4.078, p = 0.043; log-rank test). ABRACL protein levels (low ABRACL, n = 172, high ABRACL, n = 171) in gastric cancer tissues (primary data from www.kmplot.com ) are significantly correlated with poor overall survival (χ2 = 4.305, p = 0.038, log-rank test). Our results indicate that ABRACL is highly expressed in gastric cancer and is a potential prognostic marker and therapeutic target for this disease.


Cytological events during zygote formation of the fern Ceratopteris thalictroides.
The cytological events, including nuclear fusion, digestion of male organelles and rebuilding of the plasmalemma and cell wall, during zygote formation of the fern Ceratopteris thalictroides (L.) Brongn. are described based on the observations of transmission electron microscopy. When the spermatozoid enters the egg and contacts the cytoplasm, the male chromatin relaxes continually. The microtubular ribbon (MTr) is separated from the male nucleus and then an envelope reappears around the male nucleus. During nuclear fusion, the egg nucleus becomes highly irregular and extends some nuclear protrusions. It is proposed that the protrusions fuse with the male nucleus actively. After nuclear fusion the irregular zygotic nucleus contracts gradually. It becomes spherical before the zygote divides. The male chromatin is identifiable as fibrous structure in the zygotic nucleus in the beginning, but it gradually becomes diffused completely. The male organelles, including the MTr, multilayered structure, flagella and the male mitochondria are finally digested in the zygotic cytoplasm. Finally a new plasmalemma and cell wall are formed outside the protoplast. The organelles in the zygote are rearranged, which produces a horizontal polarity zygote. The zygote divides with an oblique-vertical cell plate facing the apical notch of the gametophyte.


Effects of foliar fertilization and arbuscular mycorrhizal colonization on Salvia officinalis L. growth, antioxidant capacity, and essential oil composition.
The effect of foliar fertilization and Glomus intraradices inoculation on the growth, qualitative and quantitative pattern of essential oil in Salvia officinalis was determined. Sage plants were grown in a glass house on a soil/sand mixture (w/w = 3:1). Agroleaf total, N:P:K = 20:20:20 + microelements, was used at the whole vegetative growth stage as a 0.3% solution. Inoculation with Glomus intraradices was done at the sowing stage. Application of foliar fertilization and/or mycorrhizal colonization improved dry biomass accumulation and increased the content of antioxidant metabolites (ascorbate and reduced glutathione). Applied treatments lowered the activities of the antioxidants enzymes catalase, ascorbate peroxidase and superoxide dismutase, while guaiacol peroxidase increased. The relative quantity of essential oil pattern was also altered as a result of the applied treatments. Combined application (FF + Gi) significantly promoted 1,8-cineole and alpha-thujone, mycorrhizal colonization enhanced bornyl acetate, 1,8-cineole, alpha- and beta-thujones, while foliar fertilization increased bornyl acetate and camphor. The favorable effect of root colonization by Glomus intraradices was determined both on quantitative and qualitative pattern of sage essential oil. We conclude that inoculation with Glomus intraradices resulted in improved essential oil yield and quality, while combined application of foliar fertilizer and mycorrhizal fungi predominantly enhanced shoot biomass accumulation.


Mechanistic Unveiling of C═C Double-Bond Rotation and Origins of Regioselectivity and Product E/Z Selectivity of Pd-Catalyzed Olefinic C-H Functionalization of (E)-N-Methoxy Cinnamamide.
Density functional theory (DFT) calculations have been performed to study the Pd-catalyzed C-H functionalization of (E)-N-methoxy cinnamamide (E1), which selectively provides the α-C-H activation products (EP as minor product and its C═C rotation isomer ZP' as major product). Three crucial issues are solved: (i) The detailed mechanism leading to ZP' is one issue. The computational analyses of the mechanisms proposed in previously experimental and theoretical literature do not seem to be consistent with the experimental findings due to the high barriers involved. Alternatively, we present a novel oxidation/reduction-promoted mechanism featuring the Pd(0) → Pd(II) → Pd(0) transformation. The newly proposed mechanism involves the initial coordination of the active catalyst PdL2 (L = t-BuCN) with the C═C bond in EP, followed by the oxidative cyclization/reductive decyclization-assisted C═C double-bond rotation processes resulting in ZP' and regeneration of PdL2. (ii) The origin of the product E/Z selectivity is the second issue. On the basis of the calculated results, it is found that, at the initial stage of the reaction, EP is certainly completely generated, while no ZP' formation occurred. Once E1 is used up, EP immediately acts as the partner of the new catalytic cycle and sluggishly evolves into ZP'. A small amount of generated ZP' would reversibly transform to EP due to the higher barrier involved. (iii) The intrinsic reasons for the regioselectivity are the third issue. The calculated results indicate that the regioselectivity for α-C-H activation is mainly attributed to the stronger electrostatic attraction between the α-C and the metal center.


Isolation of a French bean (Phaseolus vulgaris L.) homolog to the beta-glucan elicitor-binding protein of soybean (Glycine max L.).
A high-affinity membrane-bound beta-glucan elicitor-binding protein has been purified from microsomal preparations of French bean (Phaseolus vulgaris L.) roots. A 5900-fold purification was achieved by affinity chromatography of functionally solubilized membrane proteins. The beta-glucan-binding protein had an apparent molecular mass of 78 kDa when subjected to SDS-PAGE. Western blot analysis showed specific crossreactivity of this French bean protein with an antiserum raised against a synthetic peptide representing an internal 15 amino acid fragment of the beta-glucan-binding protein from soybean. Northern blot analysis with a cDNA probe of the soybean beta-glucan-binding protein gene revealed a crosshybridizing transcript of 2.4 kb in French bean. These results indicate that the beta-glucan-binding proteins of French bean and soybean are conserved homologs involved in beta-glucan elicitor recognition.


Routine endoscopic retrograde cholangiography in the detection of early biliary complications after liver transplantation.
The value of routinely performing endoscopic retrograde cholangiography (ERC) to detect biliary complications in patients undergoing orthotopic liver transplantation (OLT) with duct-to-duct anastomosis without a T-tube is not known. Eighty-nine of 171 liver transplant recipients (61 men; mean age, 49.9 years) underwent ERC 14.5 +/- 4.5 (SD) days after surgery between January 1997 and August 1999. Findings of ERC and need for intervention for biliary complications were noted. ERC was successful in 71of 89 patients (80%). Nineteen patients (21%) required intervention for biliary complications (stricture, 13 patients; bile leak, 6 patients). Protocol ERC detected eight of these complications (42%). In 4 patients, ERC failed, and 7 patients with a normal ERC result subsequently required intervention (2 patients in the same admission, and 5 patients after discharge). Sensitivity, specificity, and positive and negative predictive values for successful ERC in detecting early biliary complications were 80%, 98%, 89%, and 97%, whereas those for predicting the overall rate of biliary complications were 53%, 98%, 89%, and 89%, respectively. Although highly specific and moderately sensitive in detecting early biliary complications, ERC performed routinely has low sensitivity in predicting the overall risk for biliary complications in patients undergoing OLT with unsplinted duct-to-duct anastomosis.


Increased predominance of HIV-1 CRF01_AE and its recombinants in the Philippines.
The growth rate of new HIV infections in the Philippines was the fastest of any countries in the Asia-Pacific region between 2010 and 2016. To date, HIV-1 subtyping results in the Philippines have been determined by characterizing only partial viral genome sequences. It is not known whether recombination occurs in the majority of unsequenced genome regions. Near-full-length genome (NFLG) sequences were obtained by amplifying two overlapping half genomes from plasma samples collected between 2015 and 2017 from 23 newly diagnosed infected individuals in the Philippines. Phylogenetic analysis showed that the newly characterized sequences were CRF01_AE (14), subtype B (3), CRF01/B recombinants (5) and a CRF01/CRF07/B recombinant (1). All 14 CRF01_AE formed a tight cluster, suggesting that they were derived from a single introduction. The time to the most recent common ancestor (tMRCA) for CRF01_AE in the Philippines was 1995 (1992-1998), about 10-15 years later than that of CRF01_AE in China and Thailand. All five CRF01/B recombinants showed distinct recombination patterns, suggesting ongoing recombination between the two predominant circulating viruses. The identification of partial CRF07_BC sequences in one CRF01/CRF07/B recombinant, not reported previously in the Philippines, indicated that CRF07_BC may have been recently introduced into that country from China, where CRF07_BC is prevalent. Our results show that the major epidemic strains may have shifted to an increased predominance of CRF01_AE and its recombinants, and that other genotypes such as CRF07_BC may have been introduced into the Philippines.


Glycopyrrolate and atropine inhalation: comparative effects on normal airway function.
Bronchodilation was produced in normal subjects by inhalation of high doses of a quaternary parasympatholytic agent (glycopyrrolate), and responses were compared with those of atropine and a placebo. Both drugs induced significant increases in specific airway conductance (SGaw) and forced expiratory flows, but the effects of glycopyrrolate were sustained significantly longer (greater than 6 h). Whereas atropine produced an increased heart rate (26%) and severe dry mouth in all subjects, these symptoms were absent with glycopyrrolate and placebo. Therefore, glycopyrrolate produces significant bronchodilation of long duration but free of the side effects of muscarinic blockade that characterize atropine inhalation.


Neuroimaging-detected late transient treatment-induced lesions in pediatric patients with brain tumors.
After the resection of brain tumors in pediatric patients, it can be difficult to differentiate recurrent tumor from treatment effects. Although late-delayed reactions are thought to be permanent, in this study the authors sought to characterize transient brain lesions (TBLs) in the late-delayed period that completely resolved without imaging or neurological sequelae. In a retrospective review of an institutional neuroimaging brain tumor database, 11 patients were identified who met the imaging criteria (transient T2-weighted hyperintense enhancing lesions outside of the tumor bed, which occurred after radiation and/or chemotherapy) and had undergone three-dimensional dosimetry; their radiographic, clinical, and radiation-dosimetry results were analyzed. In the 11 patients who had been treated with multiple protocols 17 loci of abnormality, including 43 discrete, asymptomatic TBLs, were detected. The median TBL diameter was 1 cm or smaller, without mass effect or necrosis, and occurred 10 months after radiation therapy, 11 months after chemotherapy, resolved by 3 months, and occurred within the high-dose radiation treatment volume (median 55.8 Gy). The findings from extended follow up revealed the development of additional permanent complications of radiation therapy within the radiation port in five of the 11 patients. A benign form of treatment-induced brain injury in children, TBLs should be treated using short-interval follow up. When these lesions are identified as a result of their characteristic imaging features, location, and temporal course, TBLs may be clearly distinguished from recurrent tumor or radiation necrosis and do not require biopsy. Further studies are needed to determine whether patients with TBLs are at an increased risk of developing more severe treatment-related brain injury.


Fentanyl Detection Using Eosin Y Paper Assays.
Eosin Y is a potential new color test for use in detecting illicit drugs that has not been extensively studied. In the present study, a variety of drugs of abuse and fentanyl analogues were tested to determine which drugs will bind to eosin Y, which functional groups are capable of binding and eliciting a color change, and a mechanism for eosin Y binding to fentanyl. Further, these agents were combined with common cutting agents and other drugs of abuse in order to determine the fentanyl detection limit in a drug mixture using an eosin Y test strip. Additionally, cobalt thiocyanate was used to determine whether the combination of cobalt thiocyanate and eosin Y has the potential to identify fentanyl. Through the testing performed, we concluded that (i) Eosin Y is capable of detecting low amounts of fentanyl down to 1%, (ii) Eosin Y binds to select tertiary amines to produce an orange to pink color change, and (iii) Eosin Y binds to the nonpiperidine ring nitrogen of fentanyl as a primary binding site and the piperidine ring nitrogen as a secondary binding site. While the cobalt thiocyanate assay detected 1% fentanyl in some of the mixtures, eosin Y detected 1% fentanyl in all mixtures. Finally, eosin Y was able to detect fentanyl in forensic case samples containing heroin and various cutting agents. Based on our results, eosin Y has the potential to screen for fentanyl and fentanyl analogues and can detect fentanyl in low amounts when mixed with common cutting agents.


Quantitative phase-contrast imaging of cells with phase-sensitive optical coherence microscopy.
We describe a method for en face phase-contrast imaging of cells with a fiber-based differential phase-contrast optical coherence microscopy system. Recorded en face images are quantitative phase-contrast maps of cells due to spatial variation of the refractive index and (or) thickness of various cellular components. Quantitative phase-contrast images of human epithelial cheek cells obtained with the fiber-based differential phase-contrast optical coherence microscopy system are presented.


Association of Plasma Vitamins and Carotenoids, DNA Methylation of LCAT, and Risk of Age-Related Macular Degeneration.
Dysregulation of lipid metabolism has been implicated in age-related macular degeneration (AMD), the leading cause of blindness among the elderly. Lecithin cholesterol acyltransferase (LCAT) is an important enzyme responsible for lipid metabolism, which could be regulated by DNA methylation during the development of various age-related diseases. This study aimed to assess the association between LCAT DNA methylation and the risk of AMD, and to examine whether plasma vitamin and carotenoid concentrations modified this association. A total of 126 cases of AMD and 174 controls were included in the present analysis. LCAT DNA methylation was detected by quantitative real-time methylation-1specific PCR (qMSP). Circulating vitamins and carotenoids were measured using reversed-phase high-performance liquid chromatography (RP-HPLC). DNA methylation of LCAT was significantly higher in patients with AMD than those in the control subjects. After multivariable adjustment, participants in the highest tertile of LCAT DNA methylation had a 5.37-fold higher risk (95% CI: 2.56, 11.28) of AMD compared with those in the lowest tertile. Each standard deviation (SD) increment of LCAT DNA methylation was associated with a 2.23-fold (95% CI: 1.58, 3.13) increased risk of AMD. There was a J-shaped association between LCAT DNA methylation and AMD risk (Pnon-linearity = 0.03). Higher concentrations of plasma retinol and β-cryptoxanthin were significantly associated with decreased levels of LCAT DNA methylation, with the multivariate-adjusted β coefficient being -0.05 (95% CI: -0.08, -0.01) and -0.25 (95% CI: -0.42, -0.08), respectively. In joint analyses of LCAT DNA methylation and plasma vitamin and carotenoid concentrations, the inverse association between increased LCAT DNA methylation and AMD risk was more pronounced among participants who had a lower concentration of plasma retinol and β-cryptoxanthin. These findings highlight the importance of comprehensively assessing LCAT DNA methylation and increasing vitamin and carotenoid status for the prevention of AMD.


Application of LC-MS and tristimulus colorimetry to assess the ageing aptitude of Syrah wine in the Condado de Huelva D.O. (Spain), a typical warm climate region.
The study of the evolutions of different wine pigment families, copigmentation/polymerisation processes and colour characteristics during the first year of ageing in oak barrel has allowed the assessment of the ageing aptitude of Syrah wines from "Condado de Huelva D.O.", a warm climate region. A total of 32 anthocyanic pigments were identified, including 14 major compounds from grape and 18 minor derivatives formed during the vinification. The anthocyanin profile changed towards more chemical complexity, being vitisin-like pyranoanthocyanins the predominant minor pigments during the first month of ageing. As wine became older, a progressive increase on the content of 4-vinylcatechin, 4-vinylphenol and 4-vinylcatechol compounds took place. Results showed that copigmentation occurred during the whole process of ageing inducing visual perceptible colour effects. Simultaneously to the copigmentation decrease, the degree of polymerisation increased during ageing, being maximum at 9 months old wines (77%). The colour of wines evolved progressively in a positive way from 3 to 9 months of ageing, becoming darker and with more vivid colour. However, from 9 to 12 months of ageing, the chemical structure of wines was negatively affected resulting in lighter, with more red-orange hues and less vivid colours. The inclusion of the chemical and colorimetric information on the PCA model allows us to reach very good discriminations among the Syrah wines with different wood contact period.


Effect of collagen fibre orientation on the Poisson's ratio and stress relaxation of skin: an ex vivo and in vivo study.
During surgical treatment skin undergoes extensive deformation, hence it must be able to withstand large mechanical stresses without damage. Therefore, understanding the mechanical properties of skin becomes important. A detailed investigation on the relationship between the three-dimensional deformation response of skin and its microstructure is conducted in the current study. This study also discloses the underlying science of skin viscoelasticity. Deformation response of skin is captured using digital image correlation, whereas micro-CT, scanning electron microscopy and atomic force microscopy are used for microstructure analysis. Skin shows a large lateral contraction and expansion (auxeticity) when stretched parallel and perpendicular to the skin tension lines, respectively. Large lateral contraction is a result of fluid exudation from the tissue, while large rotation of the stiff collagen fibres in the loading direction explains the skin auxeticity. During stress relaxation, lateral contraction and fluid effluxion from skin reveal that tissue volume loss is the intrinsic science of skin viscoelasticity. Furthermore, the results obtained from in vivo study on human skin show the relevance of the ex vivo study to physiological conditions and stretching of the skin during its treatments.


Suicide after contact with substance misuse services: a national registry study.
People with substance use disorders have a well-known increased risk for taking their own life. Previous research has mainly focused on suicide in mental health services, whereas there is limited knowledge regarding suicide after contact with substance misuse services. The aim of the current study was to describe the utilisation of both mental health services and substance misuse services among people who have died by suicide within a year of contact with substance misuse services. We used an explanatory observational design, where all suicide deaths in the period from 2009 to 2016 were retrieved from the Norwegian Cause of Death Registry and linked with the Norwegian Patient Registry. The people who had been in contact with substance misuse services within a year before their death were included in the sample (n = 419). The analysis was stratified by gender, and variables with significant differences between men and women were entered into a multivariate logistic regression model. More women (73.5%) than men (60.6%) had contact with mental health services in their last year (P = 0.01). In the adjusted logistic regression model, poisoning was more common among women (adjusted odds ratio (AOR) = 1.81, 95% CI 1.09-3.02) and women were more likely to be diagnosed with a sedative, hypnotic or anxiolytic use disorder (F14) in their last year (AOR = 2.77, 95% CI 1.37-5.68). This study highlights gender differences for suicide in substance misuse services, and the importance of collaboration and cooperation between substance misuse services and mental health services.


Extinction of high-power laser radiation under adverse weather conditions.
The propagation of laser radiation over long distances can be significantly affected by atmospheric extinction due to precipitation as well as aerosol particles and molecules. The knowledge of the contribution of precipitation is critical to the operation of a variety of laser-based systems. The study of high-power laser transmission around 1 µm is of particular interest because several atmospheric transmission windows are located in this region. To investigate the effect of adverse weather conditions on laser transmission, free-space laser transmission experiments are conducted on the DLR test range in Lampoldshausen, Germany. A high-power laser with a wavelength of 1.03 µm is used for the transmission measurements in combination with calibrated power monitors. Local weather conditions are continuously monitored by meteorological instruments during the experiments. Extinction coefficients are derived from transmission measurements showing that the extinction for snow is 7 times higher than for rain, and the extinction for drizzle/rain is 4 times higher than for rain at a given precipitation rate of 1 mm/h. For a mixture of rain and snow, the extinction is comparable to that of rain, indicating that the water content strongly influences the optical properties and thus the extinction of laser radiation in mixed precipitation. A good relationship is found between the measured extinction coefficient and visibility for drizzle and rain and a slightly larger scatter of the data for snow. Furthermore, measured extinction coefficients are compared to the extinction coefficients based on the experimental size distributions of precipitation particles and geometric optics. A reasonable agreement is obtained for rain, with no improvement taking the forward-scattering into the detector aperture into account, and a much better agreement is obtained for snow when the forward-scattering contribution is included.


The ubiquitin-specific protease 17 is involved in virus-triggered type I IFN signaling.
Viral infection initiates a series of signaling cascades that activate the transcription factors nuclear factor kappa B and interferon regulatory factor 3, which collaborate to induce transcription of genes for type I interferons (IFNs) and other cytokines. Here we report that the deubiquitinating enzyme ubiquitin-specific protease 17 (USP17) is required for virus-induced RIG-I- and melanoma differentiation-associated protein-5 (MDA5)-mediated type I IFN signaling. Knockdown of endogenous USP17 inhibited virus-, cytoplasmic poly(I:C)- and poly(dA:dT)-induced activation of the IFN-beta promoter and cellular antiviral responses. We further found that knockdown of USP17 inhibited RIG-I- and MDA5-induced but not downstream activator-induced activation of the IFN-beta promoter, which was correlated with an increase in ubiquitination levels of RIG-I and MDA5. Taken together, our findings suggest that USP17 functions through deubiquitination of RIG-I and MDA5 to regulate virus-induced type I IFN signaling.


Measurement and Data Transmission Validity of a Multi-Biosensor System for Real-Time Remote Exercise Monitoring Among Cardiac Patients.
Remote telemonitoring holds great potential to augment management of patients with coronary heart disease (CHD) and atrial fibrillation (AF) by enabling regular physiological monitoring during physical activity. Remote physiological monitoring may improve home and community exercise-based cardiac rehabilitation (exCR) programs and could improve assessment of the impact and management of pharmacological interventions for heart rate control in individuals with AF. Our aim was to evaluate the measurement validity and data transmission reliability of a remote telemonitoring system comprising a wireless multi-parameter physiological sensor, custom mobile app, and middleware platform, among individuals in sinus rhythm and AF. Participants in sinus rhythm and with AF undertook simulated daily activities, low, moderate, and/or high intensity exercise. Remote monitoring system heart rate and respiratory rate were compared to reference measures (12-lead ECG and indirect calorimeter). Wireless data transmission loss was calculated between the sensor, mobile app, and remote Internet server. Median heart rate (-0.30 to 1.10 b∙min-1) and respiratory rate (-1.25 to 0.39 br∙min-1) measurement biases were small, yet statistically significant (all P≤.003) due to the large number of observations. Measurement reliability was generally excellent (rho=.87-.97, all P<.001; intraclass correlation coefficient [ICC]=.94-.98, all P<.001; coefficient of variation [CV]=2.24-7.94%), although respiratory rate measurement reliability was poor among AF participants (rho=.43, P<.001; ICC=.55, P<.001; CV=16.61%). Data loss was minimal (<5%) when all system components were active; however, instability of the network hosting the remote data capture server resulted in data loss at the remote Internet server during some trials. System validity was sufficient for remote monitoring of heart and respiratory rates across a range of exercise intensities. Remote exercise monitoring has potential to augment current exCR and heart rate control management approaches by enabling the provision of individually tailored care to individuals outside traditional clinical environments.


Role of pharmacists in the provision of palliative care services and support in South Africa.
South Africa (SA) has high demand but inequitable access to palliative care (PC). Realising this need and the growing recognition of pharmacists' in PC globally, a study was undertaken regarding the role of pharmacists in the provision of PC services and support in SA. A descriptive cross-sectional quantitative study was conducted among 540 community and hospital pharmacists. A self-administered, closed-ended questionnaire covering knowledge, attitude, current role, future role and barriers to PC was used. Data was coded and analysed using SPSS® Version 24.0. P-values < 0.05 were considered statistically significant. Response rate was 48.7% (n = 263). Pharmacists (72.2%) were already playing a role in PC, however, only 20.5% reported frequent involvement in PC. Services provided included medicine supply (88.2%), side-effect/symptom management (82.1%), information sharing (60.8%), bereavement counselling (60.8%), treatment/care needs (57.4%) and spiritual support (52.1%). More pharmacists (96.6%) wanted to play a role in PC, beyond medicine supply to include PC team member (91.6%), medicine reviews (91.3%), referrals (80.2%) and patient visits (50.6%). Pharmacists had a good knowledge (71.4%) and a positive attitude (61.5%) towards PC despite many health system barriers such as lack of training (91.3%), inadequate clinical experience (90.5%) and insufficient resources (77.2%). Pharmacists with their high level of knowledge, positive attitude and broad scope of practice are well-placed to play a role in PC. Further strengthening and integration of their roles into the continuum of care, will encourage the involvement of more pharmacists, enhancing availability, access and resources for PC.


Modification of DNA ends can decrease end joining relative to homologous recombination in mammalian cells.
In animal cells, exogenous DNA recombines into random chromosomal sites much more frequently than it recombines into homologous sites. Free DNA ends are "recombinogenic" in both processes. To test the effects of specific ends on analogous extrachromosomal processes, we constructed a linear genome of simian virus 40 with terminal repeated sequences. After transfection into monkey cells, the model substrate can circularize by end joining (analogous to random integration) or by homologous recombination between its terminal repeats (analogous to targeted recombination). Since the two types of recombination are in competition with one another, the ratio of homologous-recombination to end-join products is a sensitive indicator of the differential effects of specific ends. Substrates with blunt ends, complementary sticky ends, or mismatched ends generated the same ratio of homologous-recombination to end-join products. However, addition of dideoxynucleotides to the 3' hydroxyls of the substrate decreased the frequency of end joining by a factor of 5-6 relative to homologous recombination. Thus, the frequency of end joining can be decreased relative to that of homologous recombination by modification of the ends of the input DNA. These results suggest an approach to altering the ratio of random to targeted integration in mammalian cells.


Variation of microstructural and optical properties in SILAR grown ZnO thin films by thermal treatment.
The influence of thermal treatment on the structural and morphological properties of the ZnO films deposited by double dip Successive ionic layer by adsorption reaction is presented. The effect of annealing temperature and time in air ambient is presented in detail. The deposited films were annealed from 200 to 400 degrees C in air and the structural properties were determined as a function of annealing temperature by XRD. The studies revealed that films were exhibiting preferential orientation along (002) plane. The other structural parameters like the crystallite size (D), micro strain (epsilon), dislocation density (delta) and stacking fault (alpha) of as-deposited and annealed ZnO films were evaluated and reported. The optical properties were also studied and the band gap of the ZnO thins films varied from 3.27 to 3.04 eV with the annealing temperature. SEM studies revealed that the hexagonal shaped grains with uniformly distributed morphology in annealed ZnO thin films. It has been envisaged using EDX analysis that the near stoichiometric composition of the film can be attained by thermal treatment during which microstructural changes do occur.


Phase behavior of different forms of ice filled with hydrogen molecules.
A hybrid grand-canonical Monte Carlo simulation has been performed to investigate the hydrogen hydrate compounds in which hydrogen molecules are stored in ice II and ice I{c}. A simple theoretical model, which can reproduce the simulation results, provides the phase diagrams of the two-component system in the pressure-composition plane. Stability enhancement of the two ice forms by hydrogen is quantified by the chemical potential calculation of water. The phase transitions among various phases including the two hydrogen hydrates are predicted as functions of pressure, hydrogen occupancy, and temperature.


Comparison of protective efficacy of subcutaneous versus intranasal immunization of mice with a Brucella melitensis lipopolysaccharide subunit vaccine.
Groups of mice were immunized either subcutaneously or intranasally with purified Brucella melitensis lipopolysaccharide (LPS) or with LPS as a noncovalent complex with Neisseria meningitidis group B outer membrane protein (LPS-GBOMP). Control mice were inoculated with sterile saline. Two doses of vaccine were given 4 weeks apart. Mice were challenged intranasally with virulent B. melitensis strain 16M 4 weeks after the second dose of vaccine. Sera, spleens, lungs, and livers of mice were harvested 8 weeks after challenge. The bacterial loads in the organs were determined by culture on brucella agar plates. Protective efficacy was determined by comparing the clearance of bacteria from organs of immunized mice with the clearance of bacteria from organs of control mice. At 8 weeks postchallenge there was significant protection from disseminated infection of spleens and livers of mice intranasally immunized with either vaccine compared to infection of control mice (P < 0.01). There was no significant difference in clearance of bacteria from the lungs of immunized mice and control mice. However, mice immunized subcutaneously with either LPS or LPS-GBOMP vaccine showed significant protection against infection of the spleen (P < 0.001), liver (P < 0.001), and lungs (P < 0.05). These results show that intranasal immunization of mice with either vaccine provided significant protection against disseminated infection of the spleen and liver but subcutaneous immunization of mice with the vaccines conferred significant protection against infection of the spleen, liver, and lungs.


Low Prevalence of Gram-Positive Isolates Showing Elevated Lefamulin MIC Results during the SENTRY Surveillance Program for 2015-2016 and Characterization of Resistance Mechanisms.
This study investigated the molecular mechanisms possibly associated with non-wild-type MICs for lefamulin among staphylococci and streptococci included in the lefamulin surveillance program from 2015 to 2016. A total of 2,919 Staphylococcus aureus, 276 coagulase-negative staphylococci (CoNS), 3,923 Streptococcus pneumoniae, 389 β-hemolytic, and 178 viridans group streptococci isolates were included in the surveillance studies. Eleven (0.3% of all S. aureus) S. aureus isolates with lefamulin MICs above the staphylococcal epidemiological cutoff (ECOFF) value (>0.25 μg/ml) were selected for this study. Eight (72.7%) S. aureus (lefamulin MIC, 0.5 to 4 μg/ml) isolates carried vga(A or E), one isolate (MIC, 32 μg/ml) carried lsa(E), one isolate (MIC, 16 μg/ml) had an alteration in L4, and one strain (MIC, 0.5 μg/ml) did not carry any of the investigated resistance mechanisms. A total of 14 (5.1% of all CoNS) CoNS isolates had lefamulin MICs (0.5 to >32 μg/ml) above the ECOFF. Similar to S. aureus, 8 (57.1%) CoNS (lefamulin MIC, 1 to 8 μg/ml) isolates carried vga(A or B), while 2 isolates (MIC, 4 to 32 μg/ml) carried cfr High genetic diversity was observed among staphylococci, although 3 S. aureus isolates belonged to sequence type 398 (ST398). Among the 3 Streptococcus agalactiae and 3 viridans group streptococci (0.1% of all streptococci surveyed) isolates selected for additional characterization, all but 1 isolate carried lsa(E). This study documents a low occurrence of surveillance isolates exhibiting a non-wild-type MIC for lefamulin, and among these isolates, vga and lsa(E) prevailed in staphylococci and streptococci, respectively.


Sustainable therapies by engineered bacteria.
The controlled in situ delivery of biologics (e.g. enzymes, cytokines, antibodies) by engineered bacteria of our microbiome will allow the sustainable production of these complex and expensive drugs locally in the human body, overcoming many of the technical and economical barriers currently associated with the global use of these potent medicines. We provide examples showing how engineered bacteria can be effective treatments against multiple pathologies, including autoimmune and inflammatory diseases, metabolic disorders, diabetes, obesity, infectious diseases and cancer, hence contributing to achieve the Global Sustainable Goal 3: ensure healthy lives and promote well-being for all at all ages.


Endovascular management of ureteroarterial fistula: a rare potentially life threatening cause of hematuria.
Ureteroarterial fistula is a rare, potentially life-threatening cause of hematuria characterized by an abnormal channel between a ureter and artery. The rarity of this condition, complexity of predisposing risk factors and intermittence of symptoms may delay or obscure its diagnosis. With a high index of suspicion and careful angiographic evaluation, embarking on this condition is not only possible but sets the stage for curative intervention. We report a case of a ureteroarterial fistula presenting with intermittent hematuria, successfully diagnosed at angiography and managed with endovascular stent graft placement.


Brownian motion model of quantization ambiguity and universality in chaotic systems.
We examine spectral equilibration of quantum chaotic spectra to universal statistics in the context of the Brownian motion model. Two competing time scales, proportional and inversely proportional to the classical relaxation time, jointly govern the equilibration process. Multiplicity of quantum systems having the same semiclassical limit is not sufficient to obtain equilibration of any spectral modes in two-dimensional systems, while in three-dimensional systems equilibration for some spectral modes is possible if the classical relaxation rate is slow. Connections are made with upper bounds on semiclassical accuracy and with fidelity decay in the presence of a weak perturbation.


Noninvasive assessment of pulse-wave velocity and flow-mediated vasodilation in anesthetized Göttingen minipigs.
Few methods for noninvasive assessment of arterial stiffness and endothelial dysfunction in porcine models are available. The aim of this study was to evaluate methods for assessment of arterial stiffness and endothelial dysfunction in anesthetized Göttingen minipigs. Pulse-wave velocity (PWV) was assessed in male Göttingen minipigs (n = 8; age approximately 60 wk) by using applanation tonometry of the carotid and femoral arteries. In addition, flow-mediated vasodilation (FMD) was assessed by using vascular ultrasonography of the brachial artery to evaluate endothelial dysfunction. To evaluate the reproducibility of the methods, minipigs were anesthetized by intravenous infusion of ketamine and midazolam and examined every other day for a total of 3 trials. Neither examination day nor systolic, diastolic, or mean arterial blood pressure statistically influenced PWV or FMD. The median interexamination coefficient of variation was 17% for PWV and 59% for FMD. Measured values of PWV corresponded largely to those in clinically healthy humans, but FMD values were lower than expected for lean, young animals. Although the ketamine-midazolam anesthesia we used has been associated with minor hemodynamic effects in vivo, in vitro studies suggest that both drugs are vasodilatory. Therefore anesthesia might have influenced the endothelial response, contributing to the modest FMD response and the concurrent high coefficients of variation that we noted. We conclude that PWV—but not FMD—showed acceptable interexamination variation for its potential application in porcine models.


Leisure time physical activity and risk of prostate cancer: a dose-response meta-analysis.
Physical activity (PA) may be a protect factor against prostate cancer (PCa). We aim to investigate and establish the potential relationship between leisure time PA and PCa. PubMed, Embase databases were searched for eligible studies (cohort) before Aug-11, 2016. We conducted a meta-analysis to pool the dose-specific effects between leisure time PA and PCa. Subgroup analysis was employed to investigate the potential variation among each group. Sensitivity analysis was used to examine whether our results were stable. Twenty-one cohort studies were identified, with a total of 803,872 subjects and 28,707 PCa cases. In our meta-analysis, no obvious evidence of non-linear relationship was observed. The RRs of each 500 MET-s/week increment of leisure time PA was 1.00 (95% CI: 0.99-1.01) for total PCa, 1.00 (95% CI: 0.98-1.01) for local PCa, and 1.00 (95% CI: 0.98-1.02) for advanced PCa. In subgroup analysis, for Americans, the RR of each 500 MET-s/week increment of leisure time PA was 1.00 (95% CI: 0.99-1.01); and for Europeans the RR was 1.00 (95% CI: 0.99-1.01). Sensitivity analysis suggested our results were stable. Current evidence based on observational studies suggests no obvious association between leisure time activity and risk of prostate cancer, regardless of total PCa, local PCa, or advanced PCa.


Oxalate (Halogeton) poisoning of sheep: certain physiopathologic changes.
Certain clinical changes associated with acute oxalate (halogeton) poisoning were determined in sheep given (by stomach tube into the rumen) a lethal dose of Halogeton glomeratus. Plasma concentrations of calcium and calcium ion activity decreased over several hours to such low levels that tetany or coma occurred and death followed. Cerebrospinal fluid concentrations of calcium did not reflect the degree of hypocalcemia. In 2 pregnant sheep administered halogeton, the plasma concentration of calcium in the fetus did not decrease despite the appearance of severe maternal hypocalcemia. Increases in plasma total inorganic phosphate and magnesium concentrations occurred as the hypocalcemia progressed. Hyperglycemia was often marked as hypocalcemia became severe; however, as hyperglycemia increased, plasma immunoreactive insulin concentrations remained inappropriately low in relation to the plasma concentration of glucose. Intravenous infusion of a calcium solution at this time was associated with marked increase in immunoreactive insulin concentration and a decrease in glucose concentration. Ruminal activity, as measured by frequency and amplitude of contractions of the rumen, was greatly reduced as hypocalcemia progressed. Seemingly, body temperature became lowered as severity of the hypocalcemia progressed. Seemingly, body temperature became lowered as severity of the hypocalcemia increased, as determined by intramuscularly or intraperitoneally implanted temperature telemetry devices. However, the occurrence of tetany and the fleece covering could either modify or reverse this decrease in body temperature.


[Neonatal erythrodermia - early manifestation of Omenn's syndrome].
Ommen's syndrome is a rare, autosomal recessive disease that is characterized by symptoms of a severe combined immune deficiency, severe infections, erythrodermia, hypereosinophilia, hepatosplenomegaly, lymphadenopathy, protracted diarrhoea, hypogammaglobulinemia and elevated serum IgE. The presented case demonstrates diagnostic problems in recognizing Omenn's syndrome. These resulted predominantly from the incomplete clinical picture of the disease in its early phase. Persistent erythrodermia was the basic manifestation of the syndrome in the initial phase. Since the occurrence of the disease is extremely rare and particular symptoms are not pathognomonic, it is their co-occurrence in association with typical immunological disorders that enabled to establish the diagnosis. Through the presentation of the above case history we should like to point to the necessity of considering Omenn's syndrome in differentiating causes of erythrodermia in neonates and infants.


Artificial intelligence (AI) molecular analysis tool assists in rapid treatment decision in lung cancer: a case report.
Leptomeningeal involvement among non-small cell lung cancer (NSCLC) patients is an aggressive form of disease that requires quick and efficient treatment. In this case report, we describe a woman in her 40s with a presenting symptom of headache that ultimately was diagnosed as leptomeningeal spread from NSCLC adenocarcinoma. We identified EGFR mutation in less than 48 hours from the biopsy using imagene-artificial intelligence's real-time algorithmic solution on the pathological diagnostic slide.


A random walk model that accounts for space occupation and movements of a large herbivore.
Animal movement has been identified as a key feature in understanding animal behavior, distribution and habitat use and foraging strategies among others. Large datasets of invididual locations often remain unused or used only in part due to the lack of practical models that can directly infer the desired features from raw GPS locations and the complexity of existing approaches. Some of them being disputed for their lack of biological justifications in their design. We propose a simple model of individual movement with explicit parameters, based on a two-dimensional biased and correlated random walk with three forces related to advection (correlation), attraction (bias) and immobility of the animal. These forces can be directly estimated using individual data. We demonstrate the approach by using GPS data of 5 red deer with a high frequency sampling. The results show that a simple random walk template can account for the spatial complexity of wild animals. The practical design of the model is also verified for detecting spatial feature abnormalities and for providing estimates of density and abundance of wild animals. Integrating even more additional features of animal movement, such as individuals' interactions or environmental repellents, could help to better understand the spatial behavior of wild animals.


Performance in an Audiovisual Selective Attention Task Using Speech-Like Stimuli Depends on the Talker Identities, But Not Temporal Coherence.
Audiovisual integration of speech can benefit the listener by not only improving comprehension of what a talker is saying but also helping a listener select a particular talker's voice from a mixture of sounds. Binding, an early integration of auditory and visual streams that helps an observer allocate attention to a combined audiovisual object, is likely involved in processing audiovisual speech. Although temporal coherence of stimulus features across sensory modalities has been implicated as an important cue for non-speech stimuli (Maddox et al., 2015), the specific cues that drive binding in speech are not fully understood due to the challenges of studying binding in natural stimuli. Here we used speech-like artificial stimuli that allowed us to isolate three potential contributors to binding: temporal coherence (are the face and the voice changing synchronously?), articulatory correspondence (do visual faces represent the correct phones?), and talker congruence (do the face and voice come from the same person?). In a trio of experiments, we examined the relative contributions of each of these cues. Normal hearing listeners performed a dual task in which they were instructed to respond to events in a target auditory stream while ignoring events in a distractor auditory stream (auditory discrimination) and detecting flashes in a visual stream (visual detection). We found that viewing the face of a talker who matched the attended voice (i.e., talker congruence) offered a performance benefit. We found no effect of temporal coherence on performance in this task, prompting an important recontextualization of previous findings.


Clinical and Radiographical Evaluation of Immediate Loading of Narrow Diameter Dental Implants.
The present study aimed to evaluate the peri-implant tissue response and marginal bone levels of immediately loaded narrow diameter dental implants. In this study, 10 patients with single maxillary anterior edentulous space were included. Implants were placed and immediate provisional crown was given without any centric or eccentric contacts. After three months, a definitive restoration was placed. All the clinical and radiographical parameters were evaluated.


Inhibition of interferon-mediated induction of indoleamine 2,3-dioxygenase in mouse lung by inhibitors of prostaglandin biosynthesis.
Inhibitors of fatty acid cyclooxygenase such as indomethacin (0.1 mM), phenylbutazone (0.3 mM), and aspirin (1 mM) were found to suppress almost completely the interferon-mediated induction of indoleamine 2,3-dioxygenase in mouse lung slices. However, phenacetin, an anti-inflammatory agent devoid of cyclooxygenase inhibitory activity, and sodium salicylate, a weak inhibitor of cyclooxygenase, were much less active under identical conditions. Glucocorticoids including dexamethasone, betamethasone, and cortisone, all of which are inhibitors of phospholipase A2, blocked induction of the dioxygenase by interferon in the nanomolar range, whereas other steroid hormones, such as aldosterone, testosterone, and 17 beta-estradiol, were all but ineffective. These results suggest that the enzymes phospholipase A2 and fatty acid cyclooxygenase, both of which are essential for the biosynthesis of prostaglandins, play an important role in the induction of indoleamine 2,3-dioxygenase by interferon.


PHENOTYPIC PLASTICITY IN THE SAILFIN MOLLY, POECILIA LATIPINNA (PISCES: POECILIIDAE). I. FIELD EXPERIMENTS.
Sailfin mollies (Poecilia latipinna) display marked interdemic variation in body size. We employed "common-garden" experiments in field enclosures to explore the potential role of environmental factors in determining the interdemic phenotypic variation in growth rate, age at maturity, and size at maturity. The largest single, consistent source of variation for all traits was family identity within populations. Environmental effects acted predominantly through family x environment interactions. There was little evidence for any intrinsic variation among populations once family heterogeneity had been accounted for. In general, when statistically significant differences existed, fish raised in a saltwater pond grew faster than their broodmates raised in a freshwater pond. Both males and females tended to mature at a smaller size and later in the freshwater pond than in the saltwater pond. The effects of the environmental conditions differed among the three years in which we performed these studies. In only one year was there a substantial difference between fish raised under the two environmental conditions. These results indicate that direct environmental effects are not strong enough to account for the differences in body size among natural populations and that intrinsic differences among natural populations are due to different frequency distributions of genotypes that are present in all populations.


Signal shape feature for automatic snore and breathing sounds classification.
Snore analysis techniques have recently been developed for sleep studies. Most snore analysis techniques require reliable methods for the automatic classification of snore and breathing sounds in the sound recording. In this study we focus on this problem and propose an automated method to classify snore and breathing sounds based on the novel feature, 'positive/negative amplitude ratio (PNAR)', to measure the shape of the sound signal. The performance of the proposed method was evaluated using snore and breathing recordings (snore: 22,643 episodes and breathing: 4664 episodes) from 40 subjects. Receiver operating characteristic (ROC) analysis showed that the proposed method achieved 0.923 sensitivity with 0.918 specificity for snore and breathing sound classification on test data. PNAR has substantial potential as a feature in the front end of a non-contact snore/breathing-based technology for sleep studies.


Effect of colloids on non-Fickian transport of strontium in sediments elucidated by continuous-time random walk analysis.
Understanding the influence of colloids on radionuclide migration is of significance to evaluate environmental risks for radioactive waste disposals. In order to formulate an appropriate modelling framework that can quantify and interpret the anomalous transport of Strontium (Sr) in the absence and presence of colloids, the continuous time random walk (CTRW) approach is implemented in this work using available experimental information. The results show that the transport of Sr and its recovery are enhanced in the presence of colloids. The causes can be largely attributed to the trap-release processes, e.g. electrostatic interactions of Sr, colloids and natural sediments, and differences in pore structures, which gave rise to the varying interstitial velocities of dissolved and, if any, colloid-associated Sr. Good agreement between the CTRW simulations and the column-scale observations is demonstrated. Regardless of the presence of colloids, the CTRW modelling captures the characteristics of non-Fickian anomalous transport (0 < β < 2) of Sr. In particular, a range of 0 < β < 1, corresponding to the cases with greater recoveries, reveal strongly non-Fickian transport with distinctive earlier arrivals and tailing effects, likely due to the physicochemical heterogeneities, i.e. the repulsive interactions and/or the macro-pores originating from local heterogeneities. The results imply that colloids can increase the Sr transport as a barrier of Sr sorption onto sediments herein, apart from often being carriers of sored radionuclides in aqueous phase. From a modelling perspective, the findings show that the established CTRW model is valid for quantifying the non-Fickian and promoted transport of Sr with colloids.


Low serum and serum-free culture of multipotential human adipose stem cells.
Adipose tissue provides an easily accessible and abundant source of putative stem cells for translational clinical research. Currently prevalent culture techniques include the use of FBS, a highly variable and undefined component, which brings with it the potential for adverse patient reactions. In an effort to eliminate the use of animal products in human adipose stem cell (ASC) cultures, we have developed two new culture methods, a very low human serum expansion medium and a completely serum-free medium. Through serial testing, a highly enriched medium formulation was developed for use with and without the addition of 0.5% human serum, an amount easily obtainable from autologous blood draws. Very low-serum culture yielded population-doubling times averaging 1.86 days in early passage, while the serum-free formulation was associated with less robust cell growth, with doubling times averaging 5.79 days. ASC in both conditions maintained its ability to differentiate into adipo-, chondro- and osteogenic lineages in vitro, despite lower expression of CD34 in early passage. Expression of ALDH, HLA, CD133, CD184, and CD31 was comparable with that seen in cells cultured in 10% FBS. These newly developed culture conditions provide a unique environment within which to study ASCs without the interference of animal serum, and allow for the rapid expansion of autologous ASCs in culture in an animal product-free environment for use in human clinical trials.


Coding Gene SNP Mapping Reveals QTL Linked to Growth and Stress Response in Brook Charr (Salvelinus fontinalis).
Growth performance and reduced stress response are traits of major interest in fish production. Growth and stress-related quantitative trait loci (QTL) have been already identified in several salmonid species, but little effort has been devoted to charrs (genus Salvelinus). Moreover, most QTL studies to date focused on one or very few traits, and little investigation has been devoted to QTL identification for gene expression. Here, our objective was to identify QTL for 27 phenotypes related to growth and stress responses in brook charr (Salvelinus fontinalis), which is one of the most economically important freshwater aquaculture species in Canada. Phenotypes included 12 growth parameters, six blood and plasma variables, three hepatic variables, and one plasma hormone level as well as the relative expression measurements of five genes of interest linked to growth regulation. QTL analysis relied on a linkage map recently built from S. fontinalis consisting of both single-nucleotide polymorphism (SNP, n = 266) and microsatellite (n =81) markers in an F(2) interstrain hybrid population (n = 171). We identified 63 growth-related QTL and four stress-related QTL across 18 of the 40 linkage groups of the brook charr linkage map. Percent variance explained, confidence interval, and allelic QTL effects also were investigated to provide insight into the genetic architecture of growth- and stress-related QTL. QTL related to growth performance and stress response that were identified could be classified into two groups: (1) a group composed of the numerous, small-effect QTL associated with some traits related to growth (i.e., weight) that may be under the control of a large number of genes or pleiotropic genes, and (2) a group of less numerous QTL associated with growth (i.e., gene expression) and with stress-related QTL that display a larger effect, suggesting that these QTL are under the control of a limited number of genes of major effect. This study represents a first step toward the identification of genes potentially linked to phenotypic variation of growth and stress response in brook charr. The ultimate goal is to provide new tools for developing Molecular Assisted Selection for this species.


The apoptotic effect of resveratrol in ovarian cancer cells is associated with downregulation of galectin-3 and stimulating miR-424-3p transcription.
This study investigated if the well-reported anti-tumor effects of resveratrol (RES) is mediated by modulation levels of galectin-3 (GAL-3), an anti-apoptotic lectin that is highly overexpressed in ovarian cancer cells. SKOV3 and OVCAR-3 OC cells were untreated or incubated with DMOS or increasing concentrations of RES (25, 50, 100 μM) for 72 hr. RES, in a dose-dependent manner and in both cell lines, induced cell death and inhibited cell migration and invasion It also downregulated Bcl-2 levels, increased cleaved caspase-3, and GAL-3 protein (but not mRNA) levels, suggesting increased breakdown. These effects were associated with reduced levels of p-NF-κB P65, p-IKKα/β, and p-Akt, major targets of Gal-3. Further investigation showed that RES enhanced levels of miR-424-3p which is able to degrade GAL-3. Conclusion: Findings of this study suggest that RES induced apoptosis in cancerous cells is associated with increased levels of miR-424-3p and reduced levels of GAL-3. PRACTICAL APPLICATIONS: This study highlights a possible mechanism by which RES could enhance cell death in OC cells and enhances their sensitivity to cisplatin. RES apoptotic effect and enhancement of OC cells to chemotherapy were associated with decreased abundance of GAL-3, a common cell survival molecule that promotes tumorigenesis and increased transcription of miR-424-3p that has the ability to degrade cellular GAL-3. These findings add a possible new mechanism by which RES acts and opens a window for further research to understand its mechanism of action.


Utility of multilocus sequence typing as an epidemiological tool for investigation of outbreaks of gastroenteritis caused by Campylobacter jejuni.
Multilocus sequence typing (MLST) has been proven useful for the study of the global population structure of Campylobacter jejuni; however, its usefulness for the investigation of outbreaks of disease caused by C. jejuni has not been proven. In this study, MLST plus sequencing of the flaA short variable region (SVR) were applied to 47 isolates from 12 outbreaks of C. jejuni infection whose relatedness has been determined previously, and the results were compared to those of serotyping and pulsed-field gel electrophoresis (PFGE). Isolates implicated in an outbreak were indistinguishable by all four subtyping methods, with sporadic isolates being distinguished from outbreak isolates. Two sporadic isolates from one outbreak were resistant to SmaI digestion and therefore nontypeable by PFGE but were differentiated from the outbreak strain by the other methods. PFGE and flaA SVR typing were the most discriminatory methods, with discriminatory indices (DI) of 0.930 and 0.923, respectively. However, an epidemic strain from one outbreak was distinguished from the other outbreak isolates by flaA SVR typing; its flaA allele was different at five nucleotides, suggesting that this change was possibly mediated by recombination. MLST was less discriminatory than PFGE and flaA SVR typing (DI = 0.859), and many of the epidemic strains possessed common sequence types (STs) including ST-8, -21, -22, and -42. However, further discrimination within STs was achieved by flaA SVR typing or PFGE. The results from this study demonstrate that a combined approach of MLST plus flaA SVR typing provides a level of discrimination equivalent to PFGE for outbreak investigations.


Co-localization of CD9 and GPIIb-IIIa (alpha IIb beta 3 integrin) on activated platelet pseudopods and alpha-granule membranes.
CD9 is a 24-kDa membrane glycoprotein expressed on the surface of human platelets and potentially involved in cellular activation and adhesion functions. This protein belongs to a recently delineated family of cell-surface antigens that span the membrane four times, called tetraspans, and found mainly in leucocytes and tumour cells. As a first approach to clarify the function of CD9, we used immunoelectron microscopy to determine the localization of this antigen in human platelets, and compared its distribution with that of the GPIIb-IIIa integrin, the platelet receptor for fibrinogen. Monoclonal antibodies against CD9 (MAb7) and GPIIb-IIIa (HP1-1D) coupled to colloidal gold of different sizes (5 and 15 nm) were incubated with intact platelets in suspension or on ultrathin sections of platelets embedded in LR white. CD9 was found in association with GPIIb-IIIa on the inner face of alpha-granule membranes. These two antigens also colocalized on pseudopods of activated platelets and in contact regions between adjacent platelets. CD63, another member of the tetraspan family, was absent from alpha-granules but was associated with lysosomal structures. Flow cytometric analysis of platelet CD9 with a series of monoclonal antibodies revealed an increased expression upon thrombin stimulation, confirming the presence of an intracellular granular pool. The observation that CD9 and GPIIb-IIIa are stored in the same intracellular structures and migrate to the same activation zones after platelet stimulation lends support to previous suggestions of a close association between CD9 and GPIIb-IIIa in human platelets and of a possible involvement of CD9 in adhesive functions of platelets.


Food Availability Is the Main Driver of Seasonal Changes in Resting Metabolic Rate in African Striped Mice (Rhabdomys pumilio).
Resting metabolic rate (RMR) influences energy allocation to survival, growth, and reproduction, and significant seasonal changes in RMR have been reported. According to one hypothesis, seasonal changes in RMR are mainly attributable to seasonal changes in ambient temperature (Ta) and food availability. Studies on species from the temperate zone indicated that food availability is the main driver. However, whether this is generally true is unknown, because studies from the tropics and subtropics, where most species live, are rare. We studied the African striped mouse (Rhabdomys pumilio) inhabiting a seasonal environment with hot dry seasons with low food availability and cold moist seasons with high food availability. Using 603 RMR measurements of 277 individuals, we investigated the relative importance of food availability and Ta on RMR during selected periods, in which one extrinsic factor varied while the other factor was relatively constant. At similar Ta, residual RMR increased with increasing levels of food availability. In contrast, different Ta did not influence residual RMR at similar levels of food availability. Thus, our study on a subtropical species gives support to the hypothesis, derived from temperate zone species, that food availability mainly drives seasonal changes in RMR.


Extensive skin ulcers in a child with juvenile dermatomyositis.
Juvenile dermatomyositis (JDM) is a multisystemic disorder. Vasculitic ulcers in JDM have been reported to involve axilla, elbow or extensor surfaces of other joints. We report a young boy with JDM who presented with extensive cutaneous ulcers involving scrotum, prepuce, gluteal region, neck, bilateral axilla, periumbilical area and bilateral elbows and popliteal fossa. His disease course was marked by several relapses and he required immunosuppression with prednisolone, subcutaneous methotrexate and intravenous cyclophosphamide. His muscle weakness improved and skin ulcers healed after 6 months of intensive immunosuppressive therapy. Children with JDM and ulcers often show increased resistance to immunosuppressive therapy. Extensive cutaneous ulcers in JDM, especially those involving the scrotum, have never been described. Awareness regarding the uncommon manifestations is important to guide appropriate therapy.


Smartphone application for women with gestational diabetes mellitus: a study protocol for a multicentre randomised controlled trial.
The promotion of a healthy diet, physical activity and measurement of blood glucose levels are essential components in the care for women with gestational diabetes mellitus (GDM). Smartphones offer a new way to promote health behaviour. The main aim is to investigate if the use of the Pregnant+ app, in addition to standard care, results in better blood glucose levels compared with current standard care only, for women with GDM. This randomised controlled trial will include 230 pregnant women with GDM followed up at 5 outpatient departments (OPD) in the greater Oslo Region. Women with a 2-hour oral glucose tolerance test (OGTT) ≥9 mmol/L, who own a smartphone, understand Norwegian, Urdu or Somali and are <33 weeks pregnant, are invited. The intervention group receives the Pregnant+ app and standard care. The control group receives standard care only. Block randomisation is performed electronically. Data are collected using self-reported questionnaires and hospital records. Data will be analysed according to the intention-to-treat principle. Groups will be compared using linear regression for the main outcome and χ2 test for categorical data and Student's t-test or Mann-Whitney-Wilcoxon test for skewed distribution. The main outcome is the glucose level measured at the 2-hour OGTT 3 months postpartum. Secondary outcomes are a change in health behaviour and knowledge about GDM, quality of life, birth weight, mode of delivery and complications for mother and child. The study is exempt from regional ethics review due to its nature of quality improvement in patient care. Our study has been approved by the Norwegian Social Science Data Services and the patient privacy protections boards governing over the recruitment sites. Findings will be presented in peer-reviewed journals and at conferences. NCT02588729, Post-results.


Advances in the treatment of prostate cancer.
Several recent advances have been made in the management of prostate cancer. Active surveillance is an increasingly attractive and reasonable approach for those with low-volume, low-risk disease. For locally advanced or localized high-risk disease, neoadjuvant and adjuvant therapies are emerging as the standard of care. Innovative uses of traditional hormonal treatments can potentially limit common side effects. Recent data also support the utility of second-line hormonal therapy. For the first time, a survival advantage with the use of chemotherapy has been established. Much work is under way to augment its efficacy with novel agents such as targeted therapeutics and tumor vaccines. Recent scientific breakthroughs suggest additional strategies in treating prostate cancer.


Arthroscopic Synovectomy and Excision of a Sesamoid in the Management of an Atypical Presentation of Avascular Necrosis of Bone: A Case Report.
Avascular necrosis of a sesamoid bone is a rare and incompletely understood entity. Furthermore, associated lesions secondary to sesamoid pathology have seldom been described in the literature. We report a case of avascular necrosis of the medial sesamoid, accompanied by severe synovitis of the first metatarsophalangeal joint, that was successfully managed with arthroscopic synovectomy and open excision of the sesamoid.


Stabilizing perovskite-substrate interfaces for high-performance perovskite modules.
The interfaces of perovskite solar cells (PSCs) are important in determining their efficiency and stability, but the morphology and stability of imbedded perovskite-substrate interfaces have received less attention than have top interfaces. We found that dimethyl sulfoxide (DMSO), which is a liquid additive broadly applied to enhance perovskite film morphology, was trapped during film formation and led to voids at perovskite-substrate interfaces that accelerated the film degradation under illumination. Partial replacement of DMSO with solid-state carbohydrazide reduces interfacial voids. A maximum stabilized power conversion efficiency (PCE) of 23.6% was realized for blade-coated p-type/intrinsic/n-type (p-i-n) structure PSCs with no efficiency loss after 550-hour operational stability tests at 60°C. The perovskite mini-modules showed certified PCEs of 19.3 and 19.2%, with aperture areas of 18.1 and 50.0 square centimeters, respectively.