Prevalence and clinical effect of caesarean scar defects in women undergoing IVF.
How common are caesarean scar defects (isthmocele) among patients who have had previous caesarean delivery undergoing IVF for secondary infertility? Does the presence of isthmocele affect the chances of success of IVF? In this cohort study, women referred to an Italian public assisted reproduction centre between January 2016 and April 2021 were retrospectively reviewed. Women with a history of caesarean delivery and an indication for IVF were selected. On the basis of the local policy, all patients with a history of caesarean section underwent saline contrast sonography (SCS). Sonographic evaluation was standardized. One hundred and forty-four women were eligible, of whom 22 declined SCS and eight decided to delay pregnancy seeking. Overall, 114 women were available for data analysis. Seventy-six women were diagnosed with caesarean scar defects, corresponding to a prevalence of 67% (95% CI 58 to 75%). Baseline characteristics of women with and without isthmocele were similar. Conversely, the clinical pregnancy rate (adjusted OR 0.31, 95% CI 0.13 to 0.72) and live birth rate (adjusted OR 038, 95% CI 0.17 to 0.86) were significantly lower among affected women. No associations between specific sonographic defect characteristics and IVF outcome could be identified. Caesarean scar defects are common among women with a history of caesarean section requiring IVF. The presence of these lesions may reduce the chance of success of the procedure.


Species diversity patterns in some present and prehistoric rodent communities.
Comparisons of prehistoric (A.D. 1100-1400) and extant cricetine-dominated rodent faunas from two locations in New Mexico and one in Arizona reveal temporal changes in both species diversity and taxonomic composition. The archaeological context of the prehistoric faunas permitted them to be dated rather accurately; paleoenvironmental inferences generated from other materials recovered in the excavations such as pollen samples, agricultural remains, and tree-ring specimens provided evidence about prehistoric environmental conditions in the study areas. Both richness and evenness components of diversity are lower in the present day faunas than in their prehistoric counterparts. At the beta (between-habitat or valley-wide) level of diversity the increased prehistoric species richness as well as the nature of the differences in present and prehistoric taxonomic composition can be accounted for by small climatic shifts which were occurring between A.D. 1100 and 1300 in the Southwest and the resultant biogeogrphic responses of certain rodent species. Alpha (or within-habitat) diversity is similar for all analyzed faunas. This suggests basic similarities in very local species packing despite observed spatial and temporal variation in valley-wide diversities. Environmental changes stemming from climatic shifts provide a reasonable explanation of the observed patterns of rodent species occurrence and diversity. Habitat destruction resulting from agricultural practies of prehistoric human populations appears to have had only a limited impact on these rodent communities.


Orabase-formulated gentian violet effectively improved oral potentially malignant disorder in vitro and in vivo.
Oral cancer is a prevalent cancer in male worldwide. Oral potentially malignant disorders (OMPDs) are the oral mucosa lesions that have high malignant transformation rate to oral cancer. The mainstay for OMPDs treatment includes carbon dioxide (CO2) laser and surgery, which may lead to the side effects of scarring and impaired function of oral cavity in the patients and reduced their willingness to receive curative therapy. Therefore, developing a non-invasive and function-preserving therapy is clinically important. Since development of a novel chemotherapeutic drug requires a lot of time and cost, we applied the high-throughput screening (HTS) approach to identify new bioactivities for FDA-approved drugs, known as drug repurposing. Through this drug repurposing approach, we discovered that gentian violet (GV), which is well known for its antibacterial, antifungal, antihelminthic, antitrypanosomal and antiviral activities, was able to induce significant cell death in DOK oral precancerous cells through ROS production. Moreover, decreased phosphorylation of p53(Ser15) and NFκB(Ser536) was required for GV-induced cell death. In vivo, 3% GV orabase effectively suppressed the progression of DMBA-induced oral precancerous lesions. In conclusion, this new formulation of GV through drug repurposing has the potential to be further developed as a therapeutic drug for OPMD clinically.


Retracted: Effect of Comprehensive Nursing on the Recovery of Gastrointestinal Function in Patients Undergoing Abdominal Operation.
[This retracts the article DOI: 10.1155/2022/1179321.].


Rapid turnover of traps in Utricularia vulgaris L.
Utricularia vulgaris growing at Wicken Fen, England, showed rapid turnover of the trapping apparatus. New groups of leaves, each bearing many traps, were produced at a rate of 1.4-2.8 groups per day from April to September, 1987. Old leaves decayed at a comparable rate, so that individual leaves survived for less than 50 days. In July, trapping efficiency of individual bladders was greatest between 1 and 6 days of age and then declined rapidly. Very few traps more than 19 days old could capture prey and most were lost from the leaves within 32 days. The lifespan of traps was closely related to their size and position on the leaves. Because of the rapidity of changes in trap condition with age, trap age is a vital consideration in any studies of the functional ecology of U. vulgaris.


Work-Life Fit During A Pandemic.
Occupational health nurses can promote resilience and encourage work-life fit by understanding organizational design and offering mental health and stress management resources.


Response of cell subpopulations in spheroids to radiation-drug combinations.
Chinese hamster V79 cells grown as multicell spheroids were treated with radiation and/or selected antineoplastic drugs (5-fluorouracil, cisplatin, doxorubicin, mitomycin, and carmustine) administered at equitoxic levels in defined preirradiation and postirradiation sequences. Clonogenicity of the treated cells was determined, and the results from conventional assays were compared with those from cell-selection experiments, using a fluorescence-activated cell sorter, to determine the degree of interaction and regions of activity of the agents. Marked sequence-dependent differences in overall toxicity were observed; drug toxicity, spheroid reoxygenation, and direct sensitization appeared to be operative to a different extent with each drug and sequence. Maximal interaction between all drugs and radiation was, however, observed when drug exposure immediately preceded irradiation.


Positions of S2, S13, S16, S17, S19 and S21 in the 30 S ribosomal subunit of Escherichia coli.
Neutron scattering distance data are presented for 33 protein pairs in the 30 S ribosomal subunit from Escherichia coli, along with the methods used for measuring distances between its exchangeable components. When combined with prior data, these new results permit the positioning of S2, S13, S16, S17, S19 and S21 in the 30 S ribosomal subunit, completing the mapping of its proteins by neutron scattering. Comparisons with other data suggest that the neutron map is a reliable guide to the quaternary structure of the 30 S subunit.


Worldwide vaccine inequality threatens to unleash the next COVID-19 variant.
The emergence of the Omicron variant (B.1.1.529 BA.1) near Johannesburg heralded the development of an unprecedented number of new COVID-19 infections across South Africa in November 2021. Omicron and its subvariants would soon become the dominant strains across Africa, Europe, and the United States. As with the Delta variant (B.1.617.2), Omicron emerged from an industrialized nation with one of the lowest vaccination rates of any well-developed country. The emergence of variants from undervaccinated regions is a direct consequence of the virus replicating unchecked through an unprotected population. Despite this, the United States and other higher-income nations have adopted a strategy of preferentially inoculating their citizens with multiple and booster doses, whereas lower-income nations struggle with vaccine availability, infrastructure, and their own vaccine manufacturing capability. Much more needs to be done to address worldwide vaccine inequities and prevent the emergence of the next devastating variant. The persistence of the pandemic anywhere remains an ongoing threat to citizens everywhere.


Effects of obesity on growth and puberty.
Nutrition is an important regulator of the tempo of human growth. Infancy may represent a critical "window" where variations in nutrition have longer-term consequences for growth and development. Rapid weight gain during infancy is associated with accelerated growth and early pubertal development. Rapid weight gain in infancy is also associated with the development of insulin resistance and an exaggerated adrenarche. Such circulating hormonal changes, together with elevated leptin levels and integral effects of fat cells on hormone action through local 11beta-steroid dehydrogenase and aromatase activity could effect rate of progression of pubertal development in obese subjects. The secular trends in growth and maturation are partly attributed to changing nutrition. Recent data suggest that age at menarche may be static, but there is a debate as to whether the first signs of puberty are being seen much earlier in obese girls. Rapid early weight gain, obesity and early development may have implications for later health through the development of PCOS and overall association with cancer risk.


A newly recognized neuroectodermal syndrome of familial alopecia, anosmia, deafness, and hypogonadism.
We describe a large, three generation kindred in which 16 individuals were affected with alopecia, hyposmia or anosmia, conductive deafness associated with protruding ears, microtia, and/or atresia of the external auditory canal, hypogonadotropic hypogonadism due to LH/FSH deficiency, and a greater than normal tendency to dental caries. Variable manifestations include mild facial asymmetry, mental retardation, congenital heart defect, and cleft palate. This seems to be a previously undescribed pleiotropic autosomal dominant trait with variable expressivity. The manifestations can be explained on the basis of involvement of the ectoderm and neuroectoderm of the first and second branchial arches, of Rathke's pouch, and of the diencephalon.


Changes in beta-2 adrenergic receptor sensitivity with maturation of erythroid progenitor cells.
Erythroid burst forming units (BFU-E) were much more sensitive to the beta-2 selective adrenergic drug, salbutamol, than erythroid colony forming units (CFU-E) in an in vitro study of erythroid progenitor cells.


C11orf95-RELA reprograms 3D epigenome in supratentorial ependymoma.
Supratentorial ependymoma (ST-EPN) is a type of malignant brain tumor mainly seen in children. Since 2014, it has been known that an intrachromosomal fusion C11orf95-RELA is an oncogenic driver in ST-EPN [Parker et al. Nature 506:451-455 (2014); Pietsch et al. Acta Neuropathol 127:609-611 (2014)] but the molecular mechanisms of oncogenesis are unclear. Here we show that the C11orf95 component of the fusion protein dictates DNA binding activity while the RELA component is required for driving the expression of ependymoma-associated genes. Epigenomic characterizations using ChIP-seq and HiChIP approaches reveal that C11orf95-RELA modulates chromatin states and mediates chromatin interactions, leading to transcriptional reprogramming in ependymoma cells. Our findings provide important characterization of the molecular underpinning of C11orf95-RELA fusion and shed light on potential therapeutic targets for C11orf95-RELA subtype ependymoma.


Epitope-tagging vectors designed for yeast.
In order to facilitate the process of epitope-tagging of yeast proteins, we have constructed two Saccharomyces cerevisiae-Escherichia coli shuttle vectors that allow fusion of a sequence encoding an epitope of the human c-myc protein at the 3' end of any gene. An example of the use of this technique is presented.


The role of static features of males in the mate choice behavior of female Japanese quail (Coturnix japonica).
In two experiments, we investigated the mate choice behavior of female Japanese quail toward taxidermically-prepared male models. Both experiments consisted of four phases: (1) habituation; (2) a pre-test in which two taxidermically-prepared models of male birds were presented; (3) observation in which the respective non-preferred male model was presented either alone or with another stimulus, and (4) a post-test in which male models were again presented alone. Results showed that focal females increased their preference for a non-preferred male model that they had previously observed with a live female (Experiment 1) or with a taxidermically-prepared female model (Experiment 2). Two control groups ruled out the possibility that focal females were choosing male models either because: (1) males were presented with an additional stimulus, or (2) females were choosing an area where they observed male models with other females. The findings suggest that female quail may utilize static, species-specific features of male conspecifics in mate choice.


Case report: a case of eruptive collagenoma occurring in esophagus and intestine.
Eruptive collagenoma is a rare disease. All of the previously reported cases were located on the skin. Here we report such a case occurring in esophagus and intestine. Our patient is a Chinese woman. Two years ago, hundreds of small nodules were identified in her esophagus and intestine. The lesions were characterized by thickened hyalinized collagen fibers and haphazard neoplastic stellate cells. The tumor cells showed generally positive for vimentin and negative for h-CALD, CD34, desmin, CD163, AE1/AE3, CK7 and CK20. The nodules were blue with Masson Trichrome stain. The clinicopathological, immunohistochemical and histochemical features of the tumor were consistent with eruptive collagenoma. The patient was not given specific treatment after diagnosis, and a routine examination indicated that there was no progress for 2 years. Hitherto, this is the first case of eruptive collagenoma to have been reported occurring in esophagus and intestine.


Multi-modal depression detection based on emotional audio and evaluation text.
Early detection of depression is very important for the treatment of patients. In view of the current inefficient screening methods for depression, the research of depression identification technology is a complex problem with application value. Our research propose a new experimental method for depression detection based on audio and text. 160 Chinese subjects are investigated in this study. It is worth noting that we propose a text reading experiment to make subjects emotions change rapidly. It will be called Segmental Emotional Speech Experiment (SESE) below. We extract 384-dimensional Low-level audio features to find the differences of different emotional change in SESE. At the same time, our research propose a multi-modal fusion method based on DeepSpectrum features and word vector features to detect depression by using deep learning. Our experiment proved that SESE can improve the recognition accuracy of depression and found differences in Low-level audio features. Case group and Control group, gender and age are grouped for verification. It is also satisfactory that the multi-modal fusion model achieves accuracy of 0.912 and F1 score of 0.906. Our contribution is twofold. First, we propose and verify SESE, which can provide a new experimental idea for the follow-up researchers. Secondly, a new efficient multi-modal depression recognition model is proposed.


The effects of chronic smoking on the pathology of alcohol-related brain damage.
Both pathological and neuroimaging studies demonstrate that chronic alcohol abuse causes brain atrophy with widespread white matter loss limited gray matter loss. Recent neuroimaging studies suggest that tobacco smoking also causes brain atrophy in both alcoholics and neurologically normal individuals; however, this has not been confirmed pathologically. In this study, the effects of smoking and the potential additive effects of concomitant alcohol and tobacco consumption were investigated in autopsied human brains. A total of 44 cases and controls were divided into four groups: 16 non-smoking controls, nine smoking controls, eight non-smoking alcoholics, and 11 smoking alcoholics. The volumes of 26 gray and white matter regions were measured using an established point-counting technique. The results showed trends for widespread white matter loss in alcoholics (p < 0.007) but no effect on gray matter regions. In contrast, smoking alone had no effect on brain atrophy and the combination of smoking and alcohol showed no additional effect. Neuronal density was analyzed as a more sensitive assay of gray matter integrity. Similar to the volumetric analysis, there was a reduction in neurons (29%) in the prefrontal cortex of alcoholics, albeit this was only a trend when adjusted for potential confounders (p < 0.06). There were no smoking or combinatorial effects on neuronal density in any of the three regions examined. These results do not support the hypothesis that smoking exacerbates alcohol-related brain damage. The trends here support previous studies that alcohol-related brain damage is characterized by focal neuronal loss and generalized white matter atrophy. These disparate effects suggest that two different pathogenic mechanisms may be operating in the alcoholic brain. Future studies using ultrastructural or molecular techniques will be required to determine if smoking has more subtle effects on the brain and how chronic alcohol consumption leads to widespread white matter loss.


Suppression of in vitro growth of virulent and avirulent herpes simplex viruses by cell-mediated immune mechanisms, antibody, and interferon.
A rounding cell-forming--GC strain, which is a variant of a syncytial giant cell-forming herpes simplex virus (+GC Miyama strain), was highly attenuated for Swiss, BALB/c nu/nu, and nu/+ mice, whereas +GC was highly virulent to all the mice tested. +GC and -GC were antigenically indistinguishable from each other by cross-neutralization and cross-immunization. Immunosuppression induced by cyclophosphamide converted the nonlethal -GC infection of mice into a fatal infection. -GC replication in tissue culture was more effectively suppressed by spleen cells immunized with either +GC or -GC than was the +GC replication. -GC replication was also inhibited more effectively by antibody or the antibody-dependent cell-mediated system than was the +GC replication. -GC is highly sensitive to mouse interferon, but +GC was relatively resistant. These findings indicate that attenuation of this avirulent -GC strain may be due to a high susceptibility of its replication to humoral and cell-mediated defense factors. The probable roles of each defense factor in recovery from the infection with virulent and attenuated herpes simplex virus are also discussed.


Microwave-assisted wet digestion with H2O2 at high temperature and pressure using single reaction chamber for elemental determination in milk powder by ICP-OES and ICP-MS.
In this work a green digestion method which only used H2O2 as an oxidant and high temperature and pressure in the single reaction chamber system (SRC-UltraWave™) was applied for subsequent elemental determination by inductively coupled plasma-based techniques. Milk powder was chosen to demonstrate the feasibility and advantages of the proposed method. Samples masses up to 500mg were efficiently digested, and the determination of Ca, Fe, K, Mg and Na was performed by inductively coupled plasma optical emission spectrometry (ICP-OES), while trace elements (B, Ba, Cd, Cu, Mn, Mo, Pb, Sr and Zn) were determined by inductively coupled plasma mass spectrometry (ICP-MS). Residual carbon (RC) lower than 918mgL(-1) of C was obtained for digests which contributed to minimizing interferences in determination by ICP-OES and ICP-MS. Accuracy was evaluated using certified reference materials NIST 1549 (non-fat milk powder certified reference material) and NIST 8435 (whole milk powder reference material). The results obtained by the proposed method were in agreement with the certified reference values (t-test, 95% confidence level). In addition, no significant difference was observed between results obtained by the proposed method and conventional wet digestion using concentrated HNO3. As digestion was performed without using any kind of acid, the characteristics of final digests were in agreement with green chemistry principles when compared to digests obtained using conventional wet digestion method with concentrated HNO3. Additionally, H2O2 digests were more suitable for subsequent analysis by ICP-based techniques due to of water being the main product of organic matrix oxidation. The proposed method was suitable for quality control of major components and trace elements present in milk powder in consonance with green sample preparation.


Short-term effects of an intravenous infusion of a nutrient solution containing amino acids, glucose and insulin on leucine turnover and amino acid metabolism in patients with liver failure.
Tolerance to an intravenous nutrient infusion containing amino acids, glucose and insulin was assessed in 12 adult patients with clinical and biochemical evidence of liver failure. In six individuals, fasting plasma amino acid patterns and turnover rates were measured by a constant intravenous infusion of [1-14C]leucine tracer. In the remaining patients the same measurements were made after a 10 h intravenous infusion of a 'standard' commercial mixture of amino acids (3.4 g/h), dextrose (20 g/h) and insulin (1.6 units/h). On the second day, conditions were crossed over and measurements were repeated. With the exception of glycine, the infusion of the amino acid-containing solution failed to significantly increase plasma amino acid content. Plasma leucine flux measurements indicated that the explanation involved a reduction in input of amino acids derived from the breakdown of body proteins rather than an increased uptake of amino acids into protein; i.e., the rate of liberation of leucine from protein decreased by an average of 2.4 mmol/h (P less than 0.05) whilst intake only added 1.6 mmol/h. No consistent changes in encephalopathy were observed. In conclusion, the infusion of the amino acid solution together with glucose and insulin resulted in improved nutritional intake and had no deleterious short-term effects on encephalopathy. However, judging from the plasma amino acid concentrations, the composition of the commercial mixture could be improved by reducing the glycine content.


Expression of recombinant carcinoembryonic-antigen-human-β-defensin-2 gene in colon cancer HCT116 cells.
The objective of this study was to construct a system driving high expression of human-β-denfensin-2 (HBD-2) system in eukaryotic cell. To construct recombinant retrovirus expression vector, CEA signal peptide-HBD-2 (mature peptide sequence) was cloned in the retrovirus expression vector PLNCX2. The retroviral vector was transfected into PT67 cells by DOTAP; after screening and amplifying single clone cell by G418, the virus particles were collected and infected to eukaryotic, colon cancer HCT116 cells. Furthermore, the HCT116 cells were also screened by using G418 and the resistance clones were obtained. Finally, the expression of HBD-2 was detected by Western blotting, which suggested a high level of expression of HBD-2 in HCT116 cells. In conclusion, the results indicate that high level of HBD-2 expression was obtained in HCT116 cells which will help in effective commercial production and purification of HBD-2 protein.


Autopsy case of V180I genetic Creutzfeldt-Jakob disease presenting with early disease pathology.
The patient was a Japanese woman who experienced a decrease in activity and gait disturbance as the initial symptoms at the age of 86, followed by disorientation and memory dysfunction. Magnetic resonance imaging showed extensive cortical regions with hyperintensity in diffusion-weighted images, and these regions showed swelling in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. The medial occipital cortex and striatum showed no apparent hyperintensity on diffusion-weighted imaging (DWI). Mild myoclonus was detected, and the patient died 10 months after the onset of symptoms; she did not enter the akinetic mutism state. The patient's brain weighed 1050 g, and neuropathological examination showed extensive characteristic various-sized and non-confluent (VaSNoC) vacuoles in the cerebral cortex. These vacuoles were observable macroscopically by loupe on images of hematoxylin and eosin-stained tissue. Gliosis, hypertrophic astrocytosis, and neuron loss were generally mild in character. Prion protein (PrP) immunostaining showed very mild diffuse-synaptic-type PrP deposition in the cerebral gray matter. These clinicopathological findings led us to several conclusions relative to the early disease pathology of V180I genetic Creutzfeldt-Jakob disease: (i) spongiform change was not found in the medial occipital cortex, which corresponds to the results of DWI; (ii) VaSNoC-type spongiform changes, extensively recognized in the cerebral cortex, corresponded to the DWI findings showing continued hyperintensity with higher brightness, and T2-weighted and FLAIR images findings showing a swelling; and (iii) spongiform changes first appear in the deeper layer and subsequently in the superficial layer in the cerebral cortex.


Impact of DNA methylation programming on normal and pre-leukemic hematopoiesis.
Epigenome regulation is a critical mechanism that governs cell identity, lineage specification and developmental cell fates. With the advent of low-input and single-cell technologies as well as sophisticated cell labeling techniques, our understanding of transcriptional and epigenetic regulation of hematopoiesis is currently undergoing dramatic changes. Increasingly, evidence suggests that the epigenome conformation acts as a critical decision-making mechanism that instructs self-renewal, differentiation and developmental fates of hematopoietic progenitor cells. When dysregulated, this leads to the evolution of disease states such as leukemia. Indeed, aberrations in DNA methylation, histone modifications and genome architecture are characteristic features of many hematopoietic neoplasms in which epigenetic enzymes are frequently mutated. Sequencing studies and characterization of the epigenetic landscape in lymphomas, leukemias and in aged healthy individuals with clonal hematopoiesis have been indispensible to identify epigenetic regulators that play a role in transformation or pre-disposition to hematopoietic malignancies. In this review, we outline the current view of the hematopoietic system and the epigenetic mechanisms regulating hematopoiesis under homeostatic conditions, with a particular focus on the role of DNA methylation in this process. We will also summarize the current knowledge on the mechanisms underlying dysregulated DNA methylation in hematologic malignancies and how this contributes to our understanding of the physiological functions of epigenetic regulators in hematopoiesis.


Self-assembled BPIV3 nanoparticles can induce comprehensive immune responses and protection against BPIV3 challenge by inducing dendritic cell maturation in mice.
Bovine parainfluenza virus type 3 (BPIV3) is one of the most important viral respiratory pathogens of cattle. No specific therapies are available for BPIV3 infection; vaccination is one of the most effective ways to prevent BPIV3 infection. We therefore prepared the self-assembled BPIV3 nanoparticles by genetically fusing the ectodomain of BPIV3 haemagglutinin-neuraminidase (HN) (HNex) to the NH2 terminus of ferritin (HNex-RFNp) using a baculovirus expression system. It was found that HNex-RFNp-induced bone marrow-derived dendritic cell (BMDC) maturation through the upregulated expression of surface molecules (MHC II, CD80, CD86, and CD40), increased the secretion of inflammatory cytokines (IL-6, IL-12, TNF-α, and IFN-γ), and reduced antigen phagocytosis and T cell activation capacity. HNex-RFNp positively regulated IκBα and NF-κB (p65) phosphorylation and facilitated NF-κB (p65) translocation into the nuclei of mature BMDCs. Incubating RFNp-treated BMDCs with TLR4 and NF-κB (p65) inhibitors, suppressed surface molecule expression as well as pro-inflammatory cytokine production and IκBα and NF-κB (p65) activities. The BPIV3 HNex protein induced BMDC maturation to some extent but was significantly weaker than HNex-RFNp. We found that HNex-RFNp induced a higher titre of specific antibodie, haemagglutinin inhibition (HI) antibody, and virus neutralisation (VN) antibody, and a comprehensive cellular immune response. We examined protection against BPIV3 challenge in a mouse model. Pathological changes were not observed in the lungs of HNex-RFNp-vaccinated mice. Levels of BPIV3 RNA and virus titres in the lungs and trachea were significantly lower in the HNex-RFNp, than HNex, inactivated BPIV3, and PBS groups. In summary, HNex-RFNp elicited better immunogenicity than HNex or inactivated BPIV3 and could be developed as an effective vaccine to protect against BPIV3 infection.


Characterization and Genome Analysis of a Zearalenone-Degrading Bacillus velezensis Strain ANSB01E.
Zearalenone, a nonsteroidal estrogenic mycotoxin mainly produced by Fusarium species, causes reproductive disorders and hyperestrogenic syndromes in animals and humans. The bacterial strain Bacillus velezensis ANSB01E, isolated from chicken cecal content, was capable of effectively degrading zearalenone in both liquid medium and mouldy corn. Moreover, Bacillus velezensis ANSB01E exhibited good antimicrobial activities against animal pathogenic bacteria, including Escherichia coli, Staphylococcus aureus, and Salmonella spp. Genome-based analysis revealed the presence of genes coding peroxiredoxin and alpha/beta hydrolase in Bacillus velezensis ANSB01E, which may be involved in zearalenone degradation. The study on the genome provides insights into the zearalenone degradation mechanisms and advances the potential application of Bacillus velezensis ANSB01E in food and feed industry.


R-wave triggering of external instrumentation during cardiac pacing.
Monitoring and diagnostic instruments often utilize electrocardiographic R-wave detection for measuring heart rate or for timing of measurement processes. During cardiac pacing stimulus artifacts commonly interfere with the operation of such instruments because they are misinterpreted as R-waves. This phenomenon creates problems in assessing the hemodynamics during gated blood-pool scans, coronary care monitoring, and intra-aortic balloon pumping. A straightforward solution is found in the nature of the electrical signals involved in which the stimulus artifacts are detected independently and are removed from the signal fed to the R-wave detector.


Pre-operative chemoradiation for sinonasal undifferentiated carcinoma of the anterior nasal cavity resected through a lateral nasal flap approach.
Sinonasal undifferentiated carcinoma (SNUC) is an exceedingly rare and aggressive tumor that carries a poor prognosis due to its non-specific presentation and advanced stage at time of diagnosis. Early detection and treatment are vital, with chemotherapy, radiation, and surgery all being viable options. The literature is sparse and there is no consensus for optimal treatment. In surgical candidates, the otolaryngologist must have a vast skill set in order to resect the tumor with wide margins and reconstruct the defect in hopes of returning the patient to their pre-morbid state. A 74-year-old female presented with a growing left nasal mass which was biopsied and found to be a sinonasal undifferentiated carcinoma originating from the anterior nasal cavity between the septum and upper lateral cartilage. The patient was treated with neo-adjuvant carboplatin with concurrent radiation, followed by resection through a lateral nasal flap. The defect was reconstructed with a contralateral septal hinge flap and septal cartilage graft with primary closure of the lateral nasal flap. Intraoperatively, no skin or cartilage invasion was noted and as such, nasal skin was spared and utilized for primary closure. At a follow-up of 3 months, the patient had no evidence of recurrence and had a well healing repair site with satisfactory cosmesis. Despite the aggressive nature of SNUC tumors, neo-adjuvant chemo-radiation and surgical intervention with functionally and aesthetically minded reconstruction can provide patients with improved outcomes and decreased morbidity.


Malate-aspartate shuttle and exogenous NADH/cytochrome c electron transport pathway as two independent cytosolic reducing equivalent transfer systems.
In mammalian cells aerobic oxidation of glucose requires reducing equivalents produced in glycolytic phase to be channelled into the phosphorylating respiratory chain for the reduction of molecular oxygen. Data never presented before show that the oxidation rate of exogenous NADH supported by the malate-aspartate shuttle system (reconstituted in vitro with isolated liver mitochondria) is comparable to the rate obtained on activation of the cytosolic NADH/cytochrome c electron transport pathway. The activities of these two reducing equivalent transport systems are independent of each other and additive. NADH oxidation induced by the malate-aspartate shuttle is inhibited by aminooxyacetate and by rotenone and/or antimycin A, two inhibitors of the respiratory chain, while the NADH/cytochrome c system remains insensitive to all of them. The two systems may simultaneously or mutually operate in the transfer of reducing equivalents from the cytosol to inside the mitochondria. In previous reports we suggested that the NADH/cytochrome c system is expected to be functioning in apoptotic cells characterized by the presence of cytochrome c in the cytosol. As additional new finding the activity of reconstituted shuttle system is linked to the amount of α-ketoglutarate generated inside the mitochondria by glutamate dehydrogenase rather than by aspartate aminotransferase.


Purification of ornithine aminotransferase by immunoadsorption.
Ornithine aminotransferase was purified by conventional biochemical methods from rat kidney, rat liver, and human liver. Affinity-purified antibodies raised to the rat kidney enzyme were used to produce an immunoadsorbent enabling a one-step purification of ornithine aminotransferase to be made from crude human liver extracts. The harsh chemical conditions often required to desorb immunoadsorbents were avoided by isolating antibodies with low functional affinity and employing an electrophoretic desorption method which allowed the enzyme activity to be retained. The close structural similarity between human and rat ornithine aminotransferase was demonstrated by immunodiffusion reactions. It was therefore possible to purify the enzyme from human liver using immobilized antibodies raised against rat kidney ornithine aminotransferase. Furthermore, desorption was more readily achieved due to the lower affinity for the human enzyme.


Estimating cardiorespiratory fitness from heart rates both during and after stepping exercise: a validated simple and safe procedure for step tests at worksites.
Step test protocols are typically based on the heart rate (HR) measured either during exercise or during recovery. This study developed a new step test protocol to estimate maximal oxygen consumption ([Formula: see text]) based on HRs measured during and after exercise, assessed the criterion validity of the model, and evaluated the protocol's test-retest reliability. The protocol estimates [Formula: see text] from HR measurements made once a minute during 3 min of step exercise and 2 min of recovery. The model was derived using a group of 118 working adults and cross-validated using a second group of 74 working adults. Furthermore, [Formula: see text] was measured using a conventional treadmill test. While multiple regression analyses were used to develop prediction equations for [Formula: see text], intraclass correlation coefficients (ICCs) were used to examine test-retest reliability. HRs during and after exercise significantly correlated with the measured [Formula: see text]. The highest correlation (r = - 0.61) was for an HR index that combined values of HRs during and after exercise. A model including age, sex, body mass index, and the HR index accounted for 60% of the variance in measured [Formula: see text] (standard error of the estimate, 4.05 mL kg-1 min-1 or 10.5%). Cross-validation analyses demonstrated good stability of the [Formula: see text] prediction models. The ICC for the HR index was 0.65 (0.53-0.74), indicating fair to good reliability. The HR index, based on a combination of HR measurements during and after stepping exercise, offers a validated [Formula: see text] estimation procedure suitable for use in the workplace.


Validity and responsiveness of the French version of the Örebro Musculoskeletal Pain Screening Questionnaire in chronic low back pain.
The assessment of a broad range of biopsychosocial aspects is important in the rehabilitation of patients with chronic low back pain (CLBP) for the prediction of outcome as well as for evaluation. The objective of this study was to test the responsiveness, construct validity and predictive value of the Örebro Musculoskeletal Pain Screening Questionnaire (OMPSQ) compared to other instruments widely used to assess biopsychosocial aspects in patients with CLBP. 111 patients with CLBP admitted to an inpatient rehabilitation completed a set of questionnaires on biopsychosocial aspects at baseline and at discharge. Ninety-eight patients responded at three months for an assessment of the return to work status. Responsiveness of the OMPSQ, the ability to detect change in the construct of interest, was investigated by a set of hypotheses on correlations with widely used questionnaires. We tested the hypothesis that the changes in the OMPSQ would vary along with the responses in the Patient's Global Impression of Change. Prediction of disability at discharge, work status at three months and time to return to work was evaluated with linear, logistic and cox regression models. The OMPSQ showed good predictive values for disability and return to work and construct validity of the instrument was corroborated. Seventy-nine percent of our hypotheses for responsiveness could be confirmed, with the OMPSQ showing the second highest change during the rehabilitation. The OMPSQ can also be applied in patients with CLBP, but for the assessment of change in psychosocial variables one should add specific questionnaires.


Moving forward: Barriers and enablers to failure to fail - A mixed methods meta-integration.
Many academics and clinicians who assess nursing students as part of their work-integrated learning experiences encounter difficulties with awarding a failing grade to students who do not meet fitness for practice standards. The aim of this study was to explore and further our understanding of assessors' experiences of failure-to-fail of nursing students within work-integrated learning. This aim was achieved through an exploratory, sequential, mixed methods research project. Guided by Invitational Theory, this programme of work included an integrated systematic review, one-on-one and focus group interviews, and finished with a survey. The results of each of the phases of this mixed methods study were integrated to provide a greater understanding of the enablers and barriers for assessors managing poor performing students to ameliorate failure to fail. Enablers identified included: assessor supports, programme flexibility, and organisational culture. The barriers included grade inflation, in appropriate student responses, organisational processes and workload. This comprehensive integration of a mixed methods study provides new and deeper understanding of the phenomenon of failure to fail. It provides clear recommendations for practical application by tertiary and clinical facilities to enhance the enablers and minimise the barriers to failure where it is warranted.


Unprecedented simultaneous enhancement in damage tolerance and fatigue resistance of zirconia/Ta composites.
Dense (>98 th%) and homogeneous ceramic/metal composites were obtained by spark plasma sintering (SPS) using ZrO2 and lamellar metallic powders of tantalum or niobium (20 vol.%) as starting materials. The present study has demonstrated the unique and unpredicted simultaneous enhancement in toughness and strength with very high flaw tolerance of zirconia/Ta composites. In addition to their excellent static mechanical properties, these composites also have exceptional resistance to fatigue loading. It has been shown that the major contributions to toughening are the resulting crack bridging and plastic deformation of the metallic particles, together with crack deflection and interfacial debonding, which is compatible with the coexistence in the composite of both, strong and weak ceramic/metal interfaces, in agreement with predictions of ab-initio calculations. Therefore, these materials are promising candidates for designing damage tolerance components for aerospace industry, cutting and drilling tools, biomedical implants, among many others.


AAGL Practice Report: Practice Guidelines for the Management of Hysteroscopic Distending Media: (Replaces Hysteroscopic Fluid Monitoring Guidelines. J Am Assoc Gynecol Laparosc. 2000;7:167-168.).
The objective of this guideline is to provide clinicians with evidence-based information about commonly used and available hysteroscopic distending media to guide them in their performance of both diagnostic and operative hysteroscopy. While necessary for the performance of hysteroscopy and hysteroscopically-directed procedures, distending media, if absorbed systemically in sufficient amounts, can have associated adverse events, including life-threatening complications. Consequently, understanding the physical properties and the potential risks associated with the use of the various distending media is critical for the safe performance of hysteroscopic procedures. This report was developed under the direction of the Practice Committee of the AAGL as a service to their members and other practicing clinicians.


Plasmin-induced smooth muscle cell proliferation requires epidermal growth factor activation through an extracellular pathway.
Plasminogen activators are used routinely for thrombolysis. They lead to the generation of the protease, plasmin, which can induce smooth muscle cell proliferation and may thus promote further intimal hyperplasia in the thrombolysed vessel. We have shown recently that plasmin induces extracellular signal-regulated kinase 1/2 (ERK1/2)-mediated cell proliferation. Plasmin can also activate metalloproteinases on the cell surface, which can release the tethered ligand heparin-binding epidermal growth factor (HB-EGF), which can in turn activate the epidermal growth factor receptor (EGFR). Murine aortic smooth muscle cells were cultured in vitro. Assays of DNA synthesis and cell proliferation, EGFR phosphorylation, and ERK1/2 activation were examined in response to plasmin in the presence and absence of the plasmin inhibitors (epsilon-aminocaproic acid and aprotinin), matrix metalloproteinase (MMP) inhibitor GM6001, HB-EGF inhibitor CRM197, HB-EGF inhibitory antibodies, EGF inhibitory antibodies, and the EGFR inhibitor AG1478. Plasmin-induced smooth muscle cell DNA synthesis, which was blocked by EGFR and HB-EGF inhibition. Plasmin-induced time-dependent EGFR phosphorylation and ERK1/2 activation, which were inhibited by AG1478. This response was dependent on the proteolytic activity of plasmin since both plasmin inhibitors blocked the response. EGFR phosphorylation by plasmin was blocked by inhibition of MMP activity and the ligand HB-EGF. EGFR phosphorylation by EGF was not interrupted by inhibition of plasmin, MMPs, or HB-EGF. Direct blockade of the EGFR prevented activation by both plasmin and EGF. Plasmin can induce smooth muscle cell proliferation through activation of EGFR by an extracellular MMP-mediated, HB-EGF-dependent process.


Tailor-made starch-based adhesives chemically modified with NaOH:urea and their applications on a cellulosic substrate.
Adhesives formulated with native starches have high viscosity, low solids content, poor bond strength and stability due to the starch retrogradation. To overcome this problem, a strategy is the starch treatment with NaOH solution combined with urea, capable of intercalating in the polymeric chains of starch. The aims of this work were to develop adhesives based on chemically modified cassava starch with different NaOH:urea ratios and to study in depth the effect induced by the addition of different concentrations of alkali and urea in the adhesive capacity of formulations that determine their subsequent application in paper-based packaging. Firmness and consistency of the adhesive increased for the 1:1 ratio while it decreased for the NaOH:urea 2:1 ratio, suggesting that the hydrolysis of polymer chains occurred. Additionally, adhesives prepared with 15 % starch maintaining NaOH:urea ratios of 0.5:1: and 1:1 exhibited the highest stress values. ATR-FTIR studies supported the results obtained. It was possible to obtain formulations with different adhesive properties with applications in paper-based packaging. From the analysis of the studied parameters, the combination of 15 % w/w cassava starch with a ratio of NaOH:urea 1:1 allows obtaining adhesives with adequate consistency and adhesive capacity which remain stable during the adhesive storage.


A new approach to community health.
This article deals with the local health care among the Shipibo-Conibo in eastern Peru. A project called AMETRA--application of traditional medicine--is functioning in the area. The aim of AMETRA is to give courses and stimulate co-operation between traditional medical practice and Western medicine. The solutions to the health problems are seen in direct relation to the socio-economic structure and to the environmental prerequisites. The aim and purposes of AMETRA are described and analysed. It is proposed that the two medical systems should co-operate in such a manner that their complementary nature is emphasized and fully utilized.


ORC proteins in the mammalian zygote.
The origin recognition complex (ORC) proteins, ORC1-6, are the first known proteins that bind DNA replication origins to mark the competency for the initiation of DNA synthesis. These proteins have complex mechanisms of assembly into the ORC complex and unexpected localizations in the mitotic chromosomes, cytoplasm, and nuclear structures. The mammalian zygote is a potentially important model that may contribute to our understanding of the mechanisms and features influencing origin establishment and in the identification of other functions of the ORC proteins. Together with expected localizations to the chromatin during G1, we found an unexpected distribution in the cytoplasm that appeared to accumulate ORC proteins suggesting potential roles for ORC subunits in mitosis and chromatin segregation. ORC1, 2, 3, and 5 all localize to the area between the separating maternal chromosomes shortly after fertilization. ORC4 forms a cage around the set of chromosomes that will be extruded during polar body formation before it binds to the chromatin shortly before zygotic DNA replication. These data suggest that the ORC proteins may also play roles in preparing the cell for DNA replication in addition to their direct role in establishing functional replication origins.


Development of the automated cleanup system for the analysis of PCDDs, PCDFs and DL-PCBs.
A new automated cleanup system for the analysis of dioxins (PCDDs, PCDFs and DL-PCBs) has been developed. It was controlled by PLC through the touch-panel. This automated cleanup system can simultaneously treat six samples in 2h, using only about 30 mL of solvent. In this study, the recovery rates of the internal standard added as cleanup spiked were between 70% and 120% in the fly ash sample. The RSDs (relative standard deviations) were below 15%. The shortest analysis time from cleanup to calculation of concentration was approximately 6h. Moreover, this automated cleanup system eliminates personal error in sample preparation and training time for the analyst, and improves the accuracy of the experiment. Additionally, this automated cleanup system allowed rapid analysis and less consumption of organic solvent.


Tweaking the social network.
Paving the way for clinical trials, a new study shows that a glutamate receptor antagonist reduces repetitive behavior and social deficits in a mouse model of autism spectrum disorder.


The diagnostic rate of inherited metabolic disorders by exome sequencing in a cohort of 547 individuals with developmental disorders.
Considering that some Inherited Metabolic Disorders (IMDs) can be diagnosed in patients with no distinctive clinical features of IMDs, we aimed to evaluate the power of exome sequencing (ES) to diagnose IMDs within a cohort of 547 patients with unspecific developmental disorders (DD). IMDs were diagnosed in 12% of individuals with causative diagnosis (177/547). There are clear benefits of using ES in DD to diagnose IMD, particularly in cases where biochemical studies are unavailable. Exome sequencing and diagnostic rate of Inherited Metabolic Disorders in individuals with developmental disorders.


Montelukast inhibits tumour necrosis factor-alpha-mediated interleukin-8 expression through inhibition of nuclear factor-kappaB p65-associated histone acetyltransferase activity.
Montelukast is a potent cysteinyl leukotriene-1 receptor antagonist possessing some anti-inflammatory effects although the molecular mechanism of these anti-inflammatory effects is unknown. In this study, we aimed to investigate the effect of montelukast on nuclear factor (NF)-kappaB-associated histone acetylation activity in phorbol myristate acetate (PMA)-differentiated U937 cells. We examined the inhibitory effects of montelukast on TNF-alpha-induced IL-8 production in PMA-differentiated U-937 cells. U-937 cells were exposed to PMA (50 ng/mL) for 48 h to allow differentiation to macrophages. Macrophages were then exposed to TNF-alpha (10 ng/mL) in the presence or absence of montelukast (0.01-10 microm) for 24 h. After this time, the concentration of IL-8 in the culture supernatant was measured by sandwich-type ELISA kit. The effect of signalling pathways on TNF-alpha-induced IL-8 release was examined pharmacologically using selective NF-kappaB/IKK2 (AS602868, 3 microm), (PD98059, 10 microm) and p38 mitogen activated protein kinase (MAPK) (SB203580, 1 microm) inhibitors. NF-kappaB DNA binding activity was measured by a DNA-binding ELISA-based assay. NF-kappaB-p65-associated histone acetyltransferase (HAT) activity was measured by immunoprecipitation linked to commercial fluorescent HAT. TNF-alpha-induced IL-8 release was suppressed by an NF-kappaB inhibitor but not by MEK or p38 MAPK inhibitors. Montelukast induced a concentration-dependent inhibition of TNF-alpha-induced IL-8 release and mRNA expression that reached a plateau at 0.1 microm without affecting cell viability. Montelukast did not affect NF-kappaB p65 activation as measured by DNA binding but suppressed NF-kappaB p65-associated HAT activity. Montelukast inhibits TNF-alpha-stimulated IL-8 expression through changes in NF-kappaB p65-associated HAT activity. Drugs targeting these enzymes may enhance the anti-inflammatory actions of montelukast.


Time-dependent effects of platelet-rich plasma on the memory and hippocampal synaptic plasticity impairment in vascular dementia induced by chronic cerebral hypoperfusion.
The present study aimed to investigate the effects of early and late administration of platelet-rich plasma (PRP) on learning-memory and hippocampal synaptic plasticity impairment in rat model of vascular dementia. Sprague-Dawley rats (6-7 weeks) were randomly divided into control, sham, 2VO + V (bilateral carotid vessel occlusion + vehicle), 2VO + E-PRP (early after 2VO), and 2VO + L-PRP (late after 2VO) groups. The injection of PRP started immediately or on the day 20 after 2VO in 2VO + E-PRP and 2VO + L-PRP, respectively, and continued until 28th day (two-time a week). The passive avoidance and Morris water maze tests were used for evaluation of fear and spatial memory formation. The in-vivo long-term potentiation (LTP) was evaluated by field-potential recording, paired-pulse ratio (PPR) and input-output (I/O) curve which were monitored as indexes for evaluation of short-term plasticity (STP) and basal-synaptic transmission (BST), respectively. The 2VO decreased PPR at inter-stimuli interval (ISI) 10 ms and BST, but injection of PRP in both treated groups rescued the PPR and BST depression. In addition, the induction of LTP, fear and spatial memory performance decreased in the 2VO + V group. However, early treatment, but not late, recovered LTP and memory. The PPR and BST improved with early and late treatment; therefore, the number and time of injection seem to be not important for recovery of BST. However, we found that LTP and memory loss rescued only with early administration. Hence, timely injection, before development of the disease, or number of injections could be critical.


Safety of gender affirming treatment in assigned female at birth transgender people and association of androgen and estrogen β receptor polymorphisms with clinical outcomes.
Gender affirming hormone treatment (GAHT) with androgens in assigned female at birth (AFAB) people with Gender Incongruence (GI) can induce and maintain variable phenotypical changes, but individual response may be genetically determined. To clarify the role of AR and ERβ polymorphisms we prospectively evaluated AFAB subjects undergoing virilizing GAHT. Fifty-two AFAB people with confirmed GI were evaluated before (T0) and after 6 (T6) and 12 months (T12) of testosterone enanthate 250 mg i.m. every 28 days. Hormone profile (testosterone, estradiol), biochemical (blood count, glyco-metabolic profile) and clinical parameters (Ferriman-Gallwey score, pelvic organs) were evaluated at each time-point, as well as number of CAG and CA repeats for AR and ERβ, respectively. All subjects have successfully achieved testosterone levels within normal male ranges and improved their degree of virilization, in absence of significant side effects. Hemoglobin, hematocrit and red blood cells were significantly increased after treatment, but within normal ranges. Ultrasound monitoring of pelvic organs showed their significant reduction already after 6 months of GATH, in absence of remarkable abnormalities. Furthermore, a lower number of CAG repeats was associated with a higher Ferriman-Gallwey score post treatment and a higher number of CA repeats was associated with uterine volume reduction. We confirmed safety and efficacy of testosterone treatment on all measured parameters. This preliminary data hints a future role of genetic polymorphisms to tailor GAHT in GI people, but evaluation on a larger cohort is necessary as the reduced sample size could limit data generalization at this stage.


Hate the wait? How social inferences can cause customers who wait longer to buy more.
Waiting is a mundane yet inevitable customer experience. Surprisingly, little research has analyzed the effects of waiting on subsequent customer behavior. The current research explores a counterintuitive effect of waiting times on behavior during a shopping trip: Longer waits, compared with shorter waits, can lead to a larger number of purchases despite generating more negative emotional reactions. Results of a field study and three lab experiments demonstrate this effect in the context of waiting for hedonic products. Consistent with a social-inference account, the experiments further show that the effect of waiting duration occurs when wait times are thought to depend on others' preferences. This article explores the multifaceted effects of waiting duration on purchase behavior of hedonic products and sheds light on the social cognitions that underlie these effects.


3D bacterial cellulose biofilms formed by foam templating.
Bacterial cellulose is a remarkable fibrous structural component of biofilms, as it forms a mechanically strong hydrogel with high water adsorption capabilities. Additionally, bacterial cellulose is biocompatible and therefore of potential interest for skin regeneration and wound healing applications. However, bacterial cellulose produced through conventional production processes at water-air interfaces lack macroporosity control, which is crucial for regenerative tissue applications. Here we demonstrate a straightforward and efficient approach to form a macroporous bacterial cellulose foam by foaming a mannitol-based media with a bacterial suspension of Gluconoacetobacter xylinus. The bacterial suspension foam is stabilized with Cremodan as a surfactant and viscosified with Xanthan preventing water drainage. Further foam stabilization occurs through cellulose formation across the foam network. As bacterial cellulose formation is influenced by the viscosity of the growth media, we fine-tuned the concentration of Xanthan to allow for bacterial cellulose formation while avoiding water drainage caused by gravity. With this simple approach, we were able to design 3D bacterial cellulose foams without any additional processing steps. We argue that this templating approach can further be used to design foamy biofilms for biotechnological approaches, increasing the surface area and therefore the yield by improving the exchange of nutrients and metabolic products.


High charge-carrier mobility enables exploitation of carrier multiplication in quantum-dot films.
Carrier multiplication, the generation of multiple electron-hole pairs by a single photon, is of great interest for solar cells as it may enhance their photocurrent. This process has been shown to occur efficiently in colloidal quantum dots, however, harvesting of the generated multiple charges has proved difficult. Here we show that by tuning the charge-carrier mobility in quantum-dot films, carrier multiplication can be optimized and may show an efficiency as high as in colloidal dispersion. Our results are explained quantitatively by the competition between dissociation of multiple electron-hole pairs and Auger recombination. Above a mobility of ~1 cm(2) V(-1) s(-1), all charges escape Auger recombination and are quantitatively converted to free charges, offering the prospect of cheap quantum-dot solar cells with efficiencies in excess of the Shockley-Queisser limit. In addition, we show that the threshold energy for carrier multiplication is reduced to twice the band gap of the quantum dots.


Application of molecular-secondary-ion mass spectrometry for drug metabolism studies. I. Direct analysis of conjugates by thin-layer chromatography-secondary-ion mass spectrometry.
Molecular-secondary-ion mass spectrometry (SIMS) is a suitable method for the analysis of nonvolatile substances such as conjugated metabolites of drugs. We have developed a simple method for the direct SIMS measurement of conjugates following thin-layer chromatography without any extraction procedure. After separation with a butanol-acetic acid-ethanol-water (3:1:1:1, v/v) system, the spot was cut out and attached to a SIMS probe. The conjugates of p-nitrophenol and 4-hydroxyantipyrine were measured. The quantitative application of the method is also discussed, using deuterium-labelled internal standards for p-nitrophenol conjugates.


Limits of optical transmission measurements with application to particle sizing techniques.
Considerable confusion exists regarding the applicability limits of the Bouguer-Lambert-Beer law of optical transmission. We review the derivation of the law and discuss its application to the optical thickness of the light-scattering medium. We demonstrate the range of applicability by presenting a method for determining particle size by measuring optical transmission at two wavelengths.


A systematic review investigating the identification, causes, and outcomes of delays in the management of chronic limb-threatening ischemia and diabetic foot ulceration.
Patients presenting with chronic limb-threatening ischemia and diabetic foot ulceration (DFU) are at high risk of major lower limb amputation. Long-standing concern exists regarding late presentation and delayed management contributing to increased amputation rates. Despite multiple guidelines existing on the management of both conditions, there is currently no accepted time frame in which to enact specialist care and treatment. This systematic review aimed to investigate potential time delays in the identification, referral, and management of both chronic limb-threatening ischemia and DFU. A systematic review conforming to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards was performed searching MEDLINE, Embase, The Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature from inception to November 14, 2018. All English-language qualitative and quantitative articles investigating or reporting the identification, causes, and outcomes of time delays within "high-income" countries (annual gross domestic product per person >$15,000) were included. Data were extracted independently by the investigators. Given the clinical crossover, both conditions were investigated together. A study protocol was designed and registered at the International Prospective Register of Systematic Reviews. A total of 4780 articles were screened, of which 32 articles, involving 71,310 patients and 1388 health care professionals, were included. Twenty-three articles focused predominantly on DFU. Considerable heterogeneity was noted, and only 12 articles were deemed of high quality. Only four articles defined a delay, but this was not consistent between studies. Median times from symptom onset to specialist health care assessment ranged from 15 to 126 days, with subsequent median times from assessment to treatment ranging from 1 to 91 days. A number of patient and health care factors were consistently reported as potentially causative, including poor symptom recognition by the patient, inaccurate health care assessment, and difficulties in accessing specialist services. Twenty articles reported outcomes of delays, namely, rates of major amputation, ulcer healing, and all-cause mortality. Although results were heterogeneous, they allude to delays being associated with detrimental outcomes for patients. Time delays exist in all aspects of the management pathway, which are in some cases considerable in length. The causes of these are complex but reflect poor patient health-seeking behaviors, inaccurate health care assessment, and barriers to referral and treatment within the care pathway. The adoption of standardized limits for referral and treatment times, exploration of missed opportunities for diagnosis, and investigation of novel strategies for providing specialist care are required to help reduce delays.


Umbilical Cord Blood: Counselling, Collection, and Banking.
To review current evidence regarding umbilical cord blood counselling, collection, and banking and to provide guidelines for Canadian health care professionals regarding patient education, informed consent, procedural aspects, and options for cord blood banking in Canada. Selective or routine collection and banking of umbilical cord blood for future stem cell transplantation for autologous (self) or allogeneic (related or unrelated) treatment of malignant and non-malignant disorders in children and adults. Cord blood can be collected using in utero or ex utero techniques. Umbilical cord blood counselling, collection, and banking, education of health care professionals, indications for cord blood collection, short- and long-term risk and benefits, maternal and perinatal morbidity, parental satisfaction, and health care costs. Published literature was retrieved through searches of Medline and PubMed beginning in September 2013 using appropriate controlled MeSH vocabulary (fetal blood, pregnancy, transplantation, ethics) and key words (umbilical cord blood, banking, collection, pregnancy, transplantation, ethics, public, private). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date limits, but results were limited to English or French language materials. Searches were updated on a regular basis and incorporated in the guideline to September 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Umbilical cord blood is a readily available source of hematopoetic stem cells used with increasing frequency as an alternative to bone marrow or peripheral stem cell transplantation to treat malignant and non-malignant conditions in children and adults. There is minimal harm to the mother or newborn provided that priority is given to maternal/newborn safety during childbirth management. Recipients of umbilical cord stem cells may experience graft-versus-host disease, transfer of infection or genetic abnormalities, or therapeutic failure. The financial burden on the health system for public cord blood banking and on families for private cord blood banking is considerable. Recommendations 1. Health care professionals should be well-informed about cord blood collection and storage and about factors that influence the volume, quality, and ability to collect a cord blood unit. (III-A) 2. Health care professionals caring for women and families who choose private umbilical cord blood banking must disclose any financial interests or potential conflicts of interest. (III-A) 3. Pregnant women should be provided with unbiased information about umbilical cord blood banking options, including the benefits and limitations of public and private banks. (III-A) 4. Health care professionals should obtain consent from mothers for the collection of umbilical cord blood prior to the onset of active labour, ideally during the third trimester, with ample time to address any questions. (III-A) 5. Health care professionals must be trained in standardized procedures (ex utero and in utero techniques) for cord blood collection to ensure the sterility and quality of the collected unit. (II-2A) 6. Umbilical cord blood should be collected with the goal of maximizing the content of hematopoietic progenitors through the volume collected. The decision to bank the unit will depend upon specific measures of graft potency. (II-2A) 7. Umbilical cord blood collection must not adversely affect the health of the mother or newborn. Cord blood collection should not interfere with delayed cord clamping. (III-E) 8. Health care professionals should inform pregnant women and their partners of the benefits of delayed cord clamping and of its impact on cord blood collection and banking. (II-2A) 9. Cord blood units collected for public or private banking can be used for biomedical research, provided consent is obtained, when units cannot be banked or when consent for banking is withdrawn. (II-3B) 10. Mothers may be approached to donate cells for biomedical research. Informed consent for research using cord blood should ideally be obtained prior to the onset of active labour or elective Caesarean section following established research ethics guidelines. (II-2A).


Who Is at Risk of Death after Renal Trauma? An Analysis of Thirty-Day Mortality after 1,799 Cases of Renal Trauma.
The aim of the study was to report the 30-day mortality (30DM) after renal trauma and identify the risk factors associated with death. The TRAUMAFUF project was a retrospective multi-institutional study including all patients with renal trauma admitted to 17 French hospitals between 2005 and 2015. The included population focused on patients of all age groups who underwent renal trauma during the study period. The primary outcome was death within 30 days following trauma. The multivariate logistic regression model with a stepwise backward elimination was used to identify predictive factors of 30DM. Data on 1,799 renal trauma were recorded over the 10-year period. There were 59 deaths within 30 days of renal trauma, conferring a 30DM rate of 3.27%. Renal trauma was directly involved in 5 deaths (8.5% of all deaths, 0.3% of all renal trauma). Multivariate stepwise logistic regression analysis revealed that age >40 years (odds ratio [OR] 2.18; 95% confidence interval [CI]: 1.20-3.99; p = 0.01), hemodynamic instability (OR 4.67; 95% CI: 2.49-9; p < 0.001), anemia (OR 3.89; 95% CI: 1.94-8.37; p < 0.001), bilateral renal trauma (OR 6.77; 95% CI: 2.83-15.61; p < 0.001), arterial contrast extravasation (OR 2.09; 95% CI: 1.09-3.96; p = 0.02), and concomitant visceral and bone injuries (OR 6.57; 95% CI: 2.41-23.14; p < 0.001) were independent predictors of 30DM. Our large multi-institutional study supports that the 30DM of 3.27% after renal trauma is due to the high degree of associated injuries and was rarely a consequence of renal trauma alone. Age >40 years, hemodynamic instability, anemia, bilateral renal trauma, arterial contrast extravasation, and concomitant visceral and bone lesions were predictors of death. These results can help clinicians to identify high-risk patients.


Bone Mineral Density Response With Denosumab in Combination With Standard or High-Dose Teriparatide: The DATA-HD RCT.
In the Denosumab and High-Dose Teriparatide Administration (DATA-HD) study, we reported that 15 months of combined high-dose (HD) teriparatide and denosumab increased mean areal bone mineral density (aBMD) at the hip and spine more than combined denosumab and standard-dose (SD) teriparatide. In the current analysis, we compare the individual rates of aBMD response between the treatment groups. Single-site, open-label, randomized controlled trial in which postmenopausal women received either teriparatide 20-μg daily (SD) or 40-μg daily (HD) given months 0 through 9, overlapped with denosumab 60 mg, given months 3 through 15 (15 months' total duration). The proportion of participants in the SD and HD groups experiencing total hip, femoral neck, and lumbar spine aBMD gains of >3%, >6%, and >9% were compared. Postmenopausal women with osteoporosis completing all study visits (n = 60). aBMD (dual x-ray absorptiometry). At the end of the 15-month treatment period, a higher proportion of women in the HD group had aBMD increases >3% (83% vs. 58%, P = .037) and >6% (45% vs. 19%, P = .034) at the total hip, and >3% at the femoral neck (86% vs. 63%, P = .044). At the lumbar spine, >3% response rates were similar, whereas the >6% and >9% response rates were greater in the HD group (100% vs. 79%, P = .012 and 93% vs. 59%, P = .003, respectively). Compared with the SD regimen, more women treated with the HD regimen achieved clinically meaningful and rapid gains in hip and spine aBMD. These results suggest that this approach may provide unique benefits in the treatment of postmenopausal osteoporosis.


A comparison of neural control of the biarticular gastrocnemius muscles between knee flexion and ankle plantar flexion.
We aimed to determine whether the neural control of the biarticular gastrocnemius medialis (GM) and lateralis (GL) muscles is joint-specific, that is, whether their control differs between isolated knee flexion and ankle plantar flexion tasks. Twenty-one male participants performed isometric knee flexion and ankle plantar flexion tasks while we recorded high-density surface electromyography (HDsEMG). First, we estimated the distribution of activation both within- and between muscles using two complementary approaches: surface EMG amplitude and motor unit activity identified from HDsEMG decomposition. Second, we estimated the level of common synaptic input between GM and GL motor units using a coherence analysis. The distribution of EMG amplitude between GM and GL was not different between tasks, which was confirmed by the analysis of motor units' discharge rate. Even though there was a significant proximal shift in GM and GL EMG amplitude during knee flexion compared with ankle plantar flexion, the magnitude of this shift was small and not confirmed via the inspection of the spatial distribution of motor unit action potentials. A significant coherence between GM and GL motor units was only observed for four (knee flexion) and three (ankle plantar flexion) participants, with no difference in the level of coherence between the two tasks. We were able to track only a few motor units across tasks, which raises the question as to whether the same motor units were activated across tasks. Our results suggest that the neural control of the GM and GL muscles is similar across their two main functions.NEW & NOTEWORTHY Several studies have focused on the neural strategies used to control the gastrocnemius medialis (GM) and lateralis (GL) during plantar flexion. However, their secondary function, i.e., knee flexion, is not often explored. We observed a robustness of the GM and GL activation strategy across tasks, which was confirmed with an analysis of the motor unit discharge characteristics. The level of common synaptic input between GM and GL motor units was low, regardless of the task.


Establishment of a novel human medulloblastoma cell line characterized by highly aggressive stem-like cells.
Medulloblastoma is a highly aggressive brain tumor and one of the leading causes of morbidity and mortality related to childhood cancer. These tumors display differential ability to metastasize and respond to treatment, which reflects their high degree of heterogeneity at the genetic and molecular levels. Such heterogeneity of medulloblastoma brings an additional challenge to the understanding of its physiopathology and impacts the development of new therapeutic strategies. This translational effort has been the focus of most pre-clinical studies which invariably employ experimental models using human tumor cell lines. Nonetheless, compared to other cancers, relatively few cell lines of human medulloblastoma are available in central repositories, partly due to the rarity of these tumors and to the intrinsic difficulties in establishing continuous cell lines from pediatric brain tumors. Here, we report the establishment of a new human medulloblastoma cell line which, in comparison with the commonly used and well-established cell line Daoy, is characterized by enhanced proliferation and invasion capabilities, stem cell properties, increased chemoresistance, tumorigenicity in an orthotopic metastatic model, replication of original medulloblastoma behavior in vivo, strong chromosome structural instability and deregulation of genes involved in neural development. These features are advantageous for designing biologically relevant experimental models in clinically oriented studies, making this novel cell line, named USP-13-Med, instrumental for the study of medulloblastoma biology and treatment.


A cytoplasmic factor involved in the expression of resistance to C8-ATC in Saccharomyces cerevisiae.
A dozen mutants of Saccharomyces cerevisiae, resistant to C8-ATC have been characterized. C8-ATC was previously established as a biologically toxic compound. Frequency of mutants (10(-7)) was typical for spontaneous mutations. One very stable mutant was characterized extensively. The genetical analysis revealed that resistance in this mutant was determined by single-gene mutation. The rho 0 cells, obtained by ethidium bromide (EB) mutagenesis of the resistant strain, were completely devoid of resistance. A large percentage of rho- cells, obtained by a moderate EB treatment of resistant cells were still able to express resistance to C8-ATC. Therefore we hypothesized that, in our particular strain, a cytoplasmic factor is involved in nuclear determination of resistance.


Metabolism of three trichothecene mycotoxins, T-2 toxin, diacetoxyscirpenol and deoxynivalenol, by bovine rumen microorganisms.
The three trichothecene mycotoxins T-2 toxin, diacetoxyscirpenol (DAS) and deoxynivalenol (DON) were incubated in vitro for 12, 24 and 48 h with rumen microorganisms obtained from a fistulated dairy cow. Gas chromatographic and gas chromatographic-mass spectrometric analyses of extracts indicated all three toxins were biotransformed to a variety of deepoxy and deacylated products. DON was partially converted to a product identified as deepoxy DON. DAS was rapidly converted to four products including 15-monoacetoxyscirpenol (MAS), scirpentriol and two new compounds identified as 15-acetoxy-3 alpha,4 beta-dihydroxytrichothec-9,12-diene (deepoxy MAS) and 3 alpha,4 beta,15-trihydroxytrichothec-9,12-diene (deepoxy scirpentriol). T-2 toxin was also completely biotransformed to the products HT-2, T-2 triol and two new metabolites identified as 15-acetoxy-3 alpha,4 beta-dihydroxy-8 alpha-(3-methylbutyryloxy) trichothec-9,12-diene (deepoxy HT-2) and 3 alpha,4 beta,15-trihydroxy-8 alpha-(3-methylbutyryloxy)trichothec-9,12-diene (deepoxy T-2 triol).


Capacity-Building for Collecting Patient-Reported Outcomes and Experiences (PRO) Data Across Hospitals.
Patient-reported outcomes and experiences (PRO) data are an integral component of health care quality measurement and PROs are now being collected by many healthcare systems. However, hospital organizational capacity-building for the collection and sharing of PROs is a complex process. We sought to identify the factors that facilitated capacity-building for PRO data collection in a nascent quality improvement learning collaborative of 16 hospitals that has the goal of improving the childbirth experience. We used standard qualitative case study methodologies based on a conceptual framework that hypothesizes that adequate organizational incentives and capacities allow successful achievement of project milestones in a collaborative setting. The 4 project milestones considered in this study were: (1) Agreements; (2) System Design; (3) System Development and Operations; and (4) Implementation. To evaluate the success of reaching each milestone, critical incidents were logged and tracked to determine the capacities and incentives needed to resolve them. The pace of the implementation of PRO data collection through the 4 milestones was uneven across hospitals and largely dependent on limited hospital capacities in the following 8 dimensions: (1) Incentives; (2) Leadership; (3) Policies; (4) Operating systems; (5) Information technology; (6) Legal aspects; (7) Cross-hospital collaboration; and (8) Patient engagement. From this case study, a trajectory for capacity-building in each dimension is discussed. The implementation of PRO data collection in a quality improvement learning collaborative was dependent on multiple organizational capacities for the achievement of project milestones.


Beliefs and intentions for skin protection and UV exposure in young adults.
To evaluate Fishbein's integrative model in predicting young adults' skin protection, sun exposure, and indoor tanning intentions. Two hundred twelve participants completed an online survey. Damage distress, self-efficacy, and perceived control accounted for 34% of the variance in skin protection intentions. Outcome beliefs and low self-efficacy for sun avoidance accounted for 25% of the variance in sun exposure intentions. Perceived damage, outcome evaluation, norms, and indoor tanning prototype accounted for 32% of the variance in indoor tanning intentions. Future research should investigate whether these variables predict exposure and protection behaviors and whether intervening can reduce young adults' skin cancer risk behaviors.


Sexual alteration in antioxidant response and esterase profile in Hyalomma anatolicum anatolicum (Acari: Ixodidae) ticks.
The objective of the study was to reveal physiological link between sex specific engorgement pattern and evading mechanism of ticks against oxidative stress as well as acaricides. Quantitative determination of nitric oxide radical scavenging, superoxide dismutase activity and reduced glutathione (GSH) concentrations in salivary gland and gut extracts of male and female Hyalomma anatolicum anatolicum (Acari: Ixodidae) ticks established significant variation in antioxidant responses between two sexes of the ticks. Higher activity of these antioxidants and GSH depletion in females clearly indicate stronger antioxidant defense in female ticks which is to combat host mediated oxidative assault during feeding for greater engorgement and reproductive stress. The females are also better equipped with the mechanism of acaricide resistance as evidenced by higher expression of esterases than males in unfed whole tick extracts in current study.


The combined effect of bacteria and Chlorella vulgaris on the treatment of municipal wastewaters.
Impacts of Chlorella vulgaris with or without co-existing bacteria on the removal of nitrogen, phosphorus and organic matter from wastewaters were studied by comparing the wastewater treatment effects between an algae-bacteria consortium and a stand-alone algae system. In the algae-bacteria system, C.vulgaris played a dominant role in the removal of nitrogen and phosphorus, while bacteria removed most of the organic matter from the wastewater. When treating unsterilized wastewater, bacteria were found to inhibit the growth of algae at >231 mg/L dissolved organic carbon (DOC). Using the algae-bacteria consortium resulted in the removal of 97% NH4(+), 98% phosphorus and 26% DOC at a total nitrogen (TN) level of 29-174 mg/L. The reaction rate constant (k) values in sterilized and unsterilized wastewaters were 2.17 and 1.92 mg NH4(+)-N/(mg algal cell ·d), respectively.


Adenosine deaminase (ADA) activity in lymphocytes of normal individuals and patients with chronic lymphatic leukaemia.
Adenosine deaminase (adenosine aminophydrolase, ADA) activity was found to be low in lymphocytes of chronic lymphatic leukaemia (CLL) patients compared to normal lymphocytes. This was determined on 42 controls and 49 CLL patients. The mean activity in normal lymphocytes was found to be 4.35 +/- 3.34 mumol/h/10(8) cells while in CLL cells it was 2.45 +/- 2.54 mumol/h/10(8) cells.


Physiology of microbes in biofilms.
Microbial biofilms are governed by an intricate interplay between physical-chemical factors and the physiological and genetic properties of the inhabiting microbes. Many of the physiological traits that are exhibited in a biofilm environment have been observed and studied previously in detail in planktonic cultures. However, their differential and combinatorial phenotypic expression in distinct subpopulations localized to different regions in a biofilm is the cause for the overall biofilm heterogeneity. In this chapter, the causes and consequences of this interplay are elaborated with a special focus on processes controlling biofilm stability and dispersal.


Ex vivo expansion of human Tregs by rabbit ATG is dependent on intact STAT3-signaling in CD4⁺ T cells and requires the presence of monocytes.
The addition of low, nondepleting doses of rabbit antithymocyte globulin (ATG) to human peripheral blood mononuclear cells has been shown to expand functional CD4(+) CD25(+) FoxP3(+) regulatory T cells (Tregs) in vitro. This report is the first to elucidate the exact cellular mechanisms of ATG-mediated Treg expansion. CD4(+) T cells require monocytes, but not other antigen presenting cell subsets, to be present in coculture to expand Tregs. However, T cells do not require direct cell-cell contact with monocytes, suggesting the importance of soluble factors. Moreover, ATG initially "reprograms" CD4(+) T cells, but not monocytes, and induces STAT3 and STAT5 signaling in CD4(+) cells. These reprogrammed CD4(+) T cells subsequently secrete GM-CSF and IL-10 only in case of intact STAT3 signaling, which in turn promote the generation of tolerogenic CD14(+) CD11c(+) dendritic cells characterized by enhanced IL-10 and decreased IL-12 production. Treg expansion following ATG treatment is accompanied by enhanced gene expression of both GM-CSF and Bcl-2, but not TGF-β, in peripheral blood mononuclear cells. These results demonstrate that ex vivo expansion of human Tregs by ATG is due to its ability to reprogram CD4(+) T cells in a STAT3-dependent but TGF-β-independent manner, leading to the generation of monocyte-derived dendritic cells with a tolerogenic cytokine profile.


Unique Impacts of Methionine Oxidation, Tryptophan Oxidation, and Asparagine Deamidation on Antibody Stability and Aggregation.
Monoclonal antibodies are attractive therapeutic agents because of their impressive biological activities and favorable biophysical properties. Nevertheless, antibodies are susceptible to various types of chemical modifications, and the impact of such modifications on antibody physical stability and aggregation remains understudied. Here, we report a systematic analysis of the impact of methionine oxidation, tryptophan oxidation, and asparagine deamidation on antibody conformational and colloidal stability, hydrophobicity, solubility, and aggregation. Interestingly, we find little correlation between the impact of these chemical modifications on antibody conformational stability and aggregation. Methionine oxidation leads to significant reductions in antibody conformational stability while having little impact on antibody aggregation except at extreme conditions (low pH and elevated temperature). Conversely, tryptophan oxidation and asparagine deamidation have little impact on antibody conformational stability while promoting aggregation at a wide range of solution conditions, and the aggregation mechanisms appear linked to unique types of reducible and nonreducible covalent crosslinks and, in some cases, to increased levels of attractive colloidal interactions. These findings highlight that even related types of chemical modifications can lead to dissimilar antibody aggregation mechanisms, and evaluating these findings for additional antibodies will be important for improving the systematic generation of antibodies with high chemical and physical stability.


Proteome signatures for stress and starvation in Bacillus subtilis as revealed by a 2-D gel image color coding approach.
In this paper we have defined proteome signatures of Bacillus subtilis in response to heat, salt, peroxide, and superoxide stress as well as after starvation for ammonium, tryptophan, glucose, and phosphate using the 2-D gel-based approach. In total, 79 stress-induced and 155 starvation-induced marker proteins were identified including 50% that are not expressed in the vegetative proteome. Fused proteome maps and a color coding approach have been used to define stress-specific regulons that are involved in specific adaptative functions (HrcA for heat, PerR and Fur for oxidative stress, RecA for peroxide, CymR and S-box for superoxide stress). In addition, starvation-specific regulons are defined that are involved in the uptake or utilization of alternative nutrient sources (TnrA, sigmaL/BkdR for ammonium; tryptophan-activated RNA-binding attenuation protein for tryptophan; CcpA, CcpN, sigmaL/AcoR for glucose; PhoPR for phosphate starvation). The general stress or starvation proteome signatures include the CtsR, Spx, sigmaL/RocR, sigmaB, sigmaH, CodY, sigmaF, and sigmaE regulons. Among these, the Spx-dependent oxidase NfrA was induced by all stress conditions indicating stress-induced protein damages. Finally, a subset of sigmaH-dependent proteins (sporulation response regulator, YvyD, YtxH, YisK, YuxI, YpiB) and the CodY-dependent aspartyl phosphatase RapA were defined as general starvation proteins that indicate the transition to stationary phase caused by starvation.


Suppression of lymphocyte apoptosis in spleen by CXCL13 after porcine circovirus type 2 infection and regulatory mechanism of CXCL13 expression in pigs.
Porcine circovirus-associated disease (PCVAD) is one of the most serious infectious diseases in pigs worldwide. The primary causative agent of PCVAD is porcine circovirus type 2 (PCV2), which can cause lymphoid depletion and immunosuppression in pigs. Our previous study demonstrated that Laiwu (LW) pigs, a Chinese indigenous pig breed, have stronger resistance to PCV2 infection than Yorkshire × Landrace (YL) pigs. In this study, we found that the YL pigs showed more severe lymphocyte apoptosis and higher viral load in the spleen tissue than LW pigs. To illustrate the differential gene expression between healthy and infected spleens, transcriptome profiling of spleen tissues from PCV2-infected and control YL pigs was compared by RNA sequencing. A total of 90 differentially expressed genes (DEGs) was identified, including CD207, RSAD2, OAS1, OAS2, MX2, ADRB3, CXCL13, CCR1, and ADRA2C, which were significantly enriched in gene ontology (GO) terms related to the defense response to virus and cell-cell signaling, and another nine DEGs, KLF11, HGF, PTGES3, MAP3K11, XDH, CYCS, ACTC1, HSPH1, and RYR2, which were enriched in GO terms related to regulation of cell proliferation or apoptosis. Among these DEGs, the CXCL13 gene, which can suppress lymphocyte apoptosis during PCV2 infection, was significantly down-regulated in response to PCV2 infection in YL but not in LW pigs. By analysis of the regulatory elements in the promoter and 3'-untranslated region (3'-UTR) of porcine CXCL13, we found that the single nucleotide polymorphism (SNP) -1014 G (LW) > A (YL) and the Sus scrofa microRNA-296-5p (ssc-miR-296-5p) participated in regulating CXCL13 expression during the response to PCV2 infection.


[Synthetic transformations of higher terpenoids. XXX. Synthesis and cytotoxic activity of betulonic acid amides with a piperidine or pyrrolidine nitroxide moiety].
The reaction of betulonic acid chloride with 4-amino-2,2,6,6-tetramethylpeperidine-1-oxyl, 3-amino-2,2,5,5-tetramethylpyrrolidine-1-oxyl and 3-aminomethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl gave corresponding triterpenoid amides. It was found that new derivatives exhibit cytotoxic activity against tumor cells CEM-13, U-937, MT-4. CCID50 value for most activity compound--N-[3-oxolup-20(29)-en-30-yl]-(2,2,6,6-tetramethylpiperidine-4-yl)-1-oxyl--was 5.7-33.1 microM.


Generation of new peptide-Fc fusion proteins that mediate antibody-dependent cellular cytotoxicity against different types of cancer cells.
Antibody-dependent cellular cytotoxicity (ADCC), a key effector function for the clinical effectiveness of monoclonal antibodies, is triggered by the engagement of the antibody Fc domain with the Fcγ receptors expressed by innate immune cells such as natural killer (NK) cells and macrophages. Here, we fused cancer cell-binding peptides to the Fc domain of human IgG1 to engineer novel peptide-Fc fusion proteins with ADCC activity. The designed fusion proteins were expressed in human embryonic kidney 293T cells, followed by purification and characterization by western blots. One of the engineered variants (WN-Fc), bound with high affinity to a wide range of solid tumor cell lines (e.g., colon, lung, prostate, skin, ovarian, and mammary tumors). Treatment of cancer cells with the engineered peptide-Fc fusions in the presence of effector NK cells potentially enhanced cytotoxicity, degranulation, and interferon-γ production by NK cells when compared to cells treated with the Fc control. The presence of competing peptides inhibited NK cell activation. Furthermore, a bispecific peptide-Fc fusion protein activated NK cells against HER-1- and/or HER-2-expressing cancer cells. Collectively, the engineered peptide-Fc fusions constitute a new promising strategy to recruit and activate NK cells against tumor cells, a primary goal of cancer immunotherapy.


[Distribution of the serum concentration of vitamin C, folic acid and vitamin B12 in a representative sample of the adult population of Catalonia (Spain)].
The subclinical deficiency of certain micronutrients (vitamin C, folic acid, vitamin B12) has been associated with disorders as cardiovascular diseases, cancer, cataracts, immunodepression and fetal neural tube defects. The purpose of this study was to determine the serum concentration of vitamin C, folic acid and vitamin B12 in the Catalan population and to examine the prevalence of deficits of these micronutrients. We studied a subsample of individuals (n = 378) from a representative sample of people aged 18 to 75 years who had participated in the study of the Nutritional Status of the Catalan Population (1992-93). Serum concentrations of vitamin C, folic acid and vitamin B12 were determined. The serum concentration of vitamin C was lower in men than in women. 4.6 and 0.5% subjects were found to have marginal and severe deficits of vitamin C, respectively. 4 and 1.6% subjects had marginal and severe deficits of folic acid, respectively. Folic acid deficit involved up to 12.9% women aged 18-34 years and up to 9.1% men within the same age group. Subjects who had a severe deficit of folic acid consumed more than 20 g/day of alcohol. The serum concentration of vitamin B12 was greater in women than in men. 1.9% individuals had a marginal deficit of this vitamin. The sample of individuals studied were found to have a correct nutritional status with regard to vitamin C, folic acid and vitamin B12. This may explain the lower incidence of cancer and ischemic heart disease associated with the Mediterranean diet.


Palmar fasciitis and arthritis: association with endometrial adenocarcinoma.
A 74-year-old woman was referred because of rheumatic symptoms consisting of pain, swelling of the hands, contracture and flexion of the fingers and severe palmar erythrosis. One year earlier she had undergone a total abdominal hysterectomy (TAH) for uterine adenocarcinoma. A paraneoplastic syndrome with palmar fasciitis and arthritis was then suspected and an evolutive peritoneal carcinomatosis was confirmed by abdominal CT scan. The patient was first treated with hormonal therapy (progestagen) and then with chemotherapy. This, associated with calcitonin, corticosteroids and physiotherapy, allowed a temporary recovery, but the patient died 10 months later from progressive peritoneal carcinomatosis.


Association of lower plasma citric acid with prolonged cough: the Nagahama study.
Little is known about the association of prolonged cough, a common and troublesome symptom, with metabolic pathways. We aimed to clarify this association using data from the Nagahama cohort, a prospective study of participants from the general population. Self-report questionnaires on prolonged cough were collected at baseline and 5-year follow-up assessments. Blood tests at follow-up were used for gas chromatography-mass spectrometry-based metabolomics. The association between metabolites and prolonged cough was examined using the partial least squares discriminant analysis and multiple regression analysis. Among the 7432 participants, 632 had newly developed prolonged cough at follow-up, which was defined as "new-onset prolonged cough". Low plasma citric acid was significantly associated with new-onset prolonged cough, even after the adjustment of confounding factors including the presence of asthma, upper airway cough syndrome (UACS), and gastroesophageal reflux disease (GERD). A similar association was observed for isocitric acid, 3-hydroxybutyric acid, and 3-hydroxyisobutyric acid. The analysis of these four metabolites revealed that citric acid had the strongest association with new-onset prolonged cough. This significant association remained even when the analysis was confined to participants with UACS or GERD at baseline or follow-up, and these associations were also observed in participants (n = 976) who had prolonged cough at follow-up regardless of baseline status. In conclusion, low blood citric acid may be associated with prolonged cough.


Complex resistivity signatures of ethanol biodegradation in porous media.
Numerous adverse effects are associated with the accidental release of ethanol (EtOH) and its persistence in the subsurface. Geophysical techniques may permit non-invasive, real time monitoring of microbial degradation of hydrocarbon. We performed complex resistivity (CR) measurements in conjunction with geochemical data analysis on three microbial-stimulated and two control columns to investigate changes in electrical properties during EtOH biodegradation processes in porous media. A Debye Decomposition approach was applied to determine the chargeability (m), normalized chargeability (m(n)) and time constant (τ) of the polarization magnitude and relaxation length scale as a function of time. The CR responses showed a clear distinction between the bioaugmented and control columns in terms of real (σ') and imaginary (σ″) conductivity, phase (ϕ) and apparent formation factor (F(app)). Unlike the control columns, a substantial decrease in σ' and increase in F(app) occurred at an early time (within 4 days) of the experiment for all three bioaugmented columns. The observed decrease in σ' is opposite to previous studies on hydrocarbon biodegradation. These columns also exhibited increases in ϕ (up to ~9 mrad) and σ″ (up to two order of magnitude higher) 5 weeks after microbial inoculation. Variations in m and m(n) were consistent with temporal changes in ϕ and σ″ responses, respectively. Temporal geochemical changes and high resolution scanning electron microscopy imaging corroborated the CR findings, thus indicating the sensitivity of CR measurements to EtOH biodegradation processes. Our results offer insight into the potential application of CR measurements for long-term monitoring of biogeochemical and mineralogical changes during intrinsic and induced EtOH biodegradation in the subsurface.