Evolutionary interplay of single nucleotide polymorphisms at the promoter region of TNF-α gene in different clinical outcomes of malaria in India.
Host genetic factors are frequently ascribed to differential malaria outcomes as a by-product of evolutionary adaptation. To this respect, Tumor Necrosis factor alpha (TNF-α), a human cytokine, is known to be associated with malaria through its differential regulation in diverse malaria manifestations. Since diversity in differential malaria outcome is uncommon in every endemic settings, possible association of TNF-α and malaria is not commonly established. In order to check for association between the occurrence of Single Nucleotide Polymorphisms (SNPs) in the TNF-α gene with different malaria manifestations, we have sequenced a 4011 bp region constituting the promoter and the whole gene of human TNF-α in 61 patients [(16 cerebral plus severe (SCM), 21 severe (SM) and 24 uncomplicated (UM)] samples in a highly malaria endemic state (Odisha) of India. Multiple sequence alignment revealed presence of six SNPs (-1031 T > C, -863C > A, -857C > T, -308G > A, -806C > T, +787C > A), out of which the -806C > T and +787C > A are novel in malaria patients in general and the +787C > A was detected for the first time in humans. Although alleles due to six different SNPs segregate differentially in the three groups of malaria (SCM, SM and UM) in the present study, interestingly, for the -1031 T > C position, the frequency of individuals possessing the homozygous rare allele was higher in the SCM group with a higher number of heterozygotes in the UM group. The Tajima's D values considering all the SNPs in a defined group were positive and statistically insignificant conforming no evolutionary constraint. However, statistically significant deviation from expectation under Hardy-Weinberg equilibrium for -1031 T > C SNP in the UM group points towards the probable role of natural selection providing some kind of protection to malaria in Odisha, India.


Effects of blood flow on [11C]raclopride binding in the brain: model simulations and kinetic analysis of PET data.
To assess the stability of different measures of receptor occupancy from [11C]raclopride (a D2 antagonist) studies with positron emission tomography, we analyze data from five test/retest studies in normal volunteers in terms of individual model parameters from a three-compartment model, the distribution volume (DV) and the ratio of DVs from a receptor-containing region of interest to a non-receptor-containing region. Large variations were found in the individual model parameters, limiting their usefulness as an indicator of change in receptor systems. The DV ratio showed the smallest variation. Individual differences were reflected in the greater intersubject variation in DV than intrasubject variation. The potential effects of blood flow on these measurements were addressed both experimentally and by simulation studies using three models that explicitly incorporate blood flow into a compartmental model that also includes receptor-ligand binding. None of the models showed any variation in the DV with changes in blood flow as long as flow was held constant during the simulation. Experimentally, blood flow was significantly reduced by hyperventilation in a human subject. The DV was found to be reduced relative to baseline in the hyperventilation study, but the DV ratio remained unchanged. The effect of elevated and reduced flow was also tested in two baboon experiments in which PCO2 was varied. Some variability in the DV ratio was observed but was not correlated with changes in blood flow. This raises the possibility that other factors indirectly related to changes in blood flow (or PCO2) may cause changes in DV, and these effects need to be considered when evaluating experimental results.


A survey of reproductive parameters in the free-ranging chimpanzees of Gombe National Park.
This study is a review of reproductive records for chimpanzees (Pan troglodytes schweinfurthii) living in Gombe National Park, Tanzania, between 1964 and 1994. Females exhibited their first full anogenital swelling at approximately 10.8 years of age. Duration of adolescent infertility averaged 2.37 years, with first conception occurring at 12.7 years and first parturition at 13.3 years. The menstrual cycles of young nulliparous females were significantly longer than those of older multiparous females (average 39.8 days versus 33.8 days). Analysis of anogenital swelling patterns indicated an average duration of 12-13 days for maximal swelling in all classes of cycle. Nulliparous and postpartum females exhibited a similar pattern of shortened detumescent phase, indicative of anovulation. Duration of gestation averaged 225.3 days (range = 208-235) with no significant fetal gender effect. When an infant lived to weaning age, the postpartum amenorrhoea of the mother averaged 3.86 years, whereas if the offspring died as an infant the mother resumed menstrual cycles an average of 35 days later. Once postpartum cycles resumed, the next conception averaged 142.5 days later if the previous infant had survived, but sooner (92.9 days later) if the previous offspring died in infancy. Interbirth interval averaged 5.15 years. Analysis of behavioural records indicated that a lower percentage of conceptions occurred during consort matings than was previously thought, suggesting additional research is needed on this topic. Detailed discussion focuses on the environmental influence on reproductive parameters described here. Future work in this area will probably identify the importance of diet-via basic nutrition and phytochemical content-in effecting the seasonal and individual differences seen in this study.


[The value of measuring intraoperative pressure in carotid endarterectomy (author's transl)].
During the last 4 years 92 operations at the carotid bifurcation were performed. In almost all cases carotid stump pressure was measured. If the stump pressure was below one third of the systemic pressure endarterectomy was done with intraluminal shunt. Under these conditions neurologic symptome deteriorated 3 times, but improved after a few days. There was no hospital mortality.


[Expression of heme oxygenase-1 and inducible nitric oxide synthase in the lungs of hyperoxia-exposed preterm rats].
To study the expression and the role of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) in preterm rats with hyperoxia-induced lung injuries. Sixty-four three-day-old preterm Sprague-Dawley rats were randomly assigned to a hyperoxia group (90% oxygen exposure) and a control group (room air exposure), with 32 rats in each group. After 3 days or 7 days of exposure, the lung activity of HO-1 and nitric oxide (NO) contents in bronchoalveolar lavage fluid (BALF), pulmonary histopathologic changes, and the cellular distribution and expression of HO-1 and iNOS in the lungs were measured. After 3 days and 7 days of exposure, the hyperoxia group showed acute lung injuries characterized by the presence of hyperaemia, red cell extravasation and inflammatory infiltration. The NO contents in BALF and the iNOS expression in the lungs increased significantly in the hyperoxia group compared with those in the control group 3 and 7 days after exposure. The expression of HO-1 in macrophages in the lungs increased significantly in the hyperoxia group compared with that in the control group 3 and 7 days after exposure. The NO contents in BALF and the iNOS and HO-1 expression in the lungs increased significantly 7 days after hyperoxia exposure compared with 3 days after hyperoxia exposure. iNOS and HO-1 levels in the lungs increase in preterm rats with hyperoxia-induced lung injuries, suggesting that iNOS and HO-1 may play roles in hyperoxia-induced pulmonary injuries.


IPO5 promotes malignant progression of esophageal cancer through activating MMP7.
Previous studies have found that IPO5 is a cancer-promoting gene. However, the role of IPO5 in esophageal cancer has not been reported. This study aims to investigate the expression characteristics of IPO5 in esophageal cancer, and to further analyze its relationship with clinical parameters and prognosis of esophageal cancer. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression of matrix metalloproteinase 7 (MMP7) in 45 pairs of tumor tissue specimens and adjacent normal ones collected from esophageal cancer patients. The correlation between IPO5 expression and clinical indicators and prognosis of esophageal cancer patients was analyzed. Meanwhile, IPO5 expression in esophageal cancer cell lines was also detected using qRT-PCR. In addition, the influence of IPO5 on esophageal cancer cell functions was analyzed using cell counting kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assays. Finally, Dual-Luciferase reporter assay and cell reverse experiments were conducted to explore its underlying mechanisms. In this experiment, qRT-PCR results indicated that IPO5 expression in tumor tissues of esophageal cancer patients was significantly higher than that in adjacent normal ones, and the difference was statistically significant. Compared with esophageal cancer patients with low expression of IPO5, those with high expression of IPO5 had higher pathological stage and lower overall survival rate. Compared with control group, the proliferation ability of esophageal cancer cells in IPO5 knockdown group was significantly decreased. In addition, Western Blot results indicated that the key protein MMP7 was conspicuously elevated in the esophageal cancer cell line after knockdown of IPO5. Dual-Luciferase reporter assay results suggested that IPO5 can specifically bind MMP7. Additionally, the cell reverse experiment demonstrated that MMP7 was responsible for IPO5-regulated malignant progression of esophageal cancer. IPO5 expression significantly increased in esophageal cancer tissues, which was associated with pathological staging and poor prognosis of esophageal cancer patients. IPO5 may promote malignant progression of esophageal cancer through the regulation of MMP7.


Coordinated regulation of β-tubulin isotypes and epithelial-to-mesenchymal transition protein ZEB1 in breast cancer cells.
The regulation of β-tubulin isotypes, the primary targets for antimitotic chemotherapeutic drugs like taxanes, has implications for drug response and drug resistance. Over the past 15 years, micro-RNAs have been studied widely as regulators of mRNA levels. For example, the tumor suppressor miR-200c was shown in cell culture to target mesenchymal genes, including ZEB1 [ Cochrane ( 2009 ) Mol. Cancer Ther. 8 ( 5 ), 1055 - 1066 ]. In that work, exogenous miR-200c was also shown to reduce β-tubulin class III, one of its predicted targets. Furthermore, decreased miR-200c and increased β-tubulin class III were associated with poor outcomes for ovarian cancer patients [ Cittelly , D.M. ( 2012 ) Mol. Cancer Ther. 11 ( 12 ), 2556 - 2565 ]. Because miR-200c targets the epithelial-to-mesenchymal inducer ZEB1, we wanted to know whether changes in ZEB1 parallel β-tubulin isotype changes, implicating β-tubulin isotypes in ZEB1-associated cell survival pathways. We found coordinated positive feedback regulation of mRNA for ZEB1 and β-tubulin isotype classes I, III, and IVB in MDA-MB-231 breast cancer cells, commonly used as a model for triple-negative breast cancers. Low levels of paclitaxel (40 nM) were found to significantly reduce mRNA levels for these tubulin genes along with a 2-3-fold increase in miR-200c. ZEB1 silencing also reduced β-tubulin isotype classes I, III, and IVB mRNA, whereas upregulation of ZEB1 was associated with increases in these isotype classes. Our work indicates that paclitaxel-induced reduction of ZEB1 and β-tubulin isotypes are, in part, due to increased activity of miR-200c. These results suggest that in aggressive breast cancers, as modeled by MDA-MB-231 cells, β-tubulin class III is a biomarker for cell survival mediated through ZEB1-induced tumor progression pathways.


5-Hy-droxy-indan-1-one.
In the title compound (5HIN), C(9)H(8)O(2), is perfectly planar as all atoms, except the H atoms of both CH(2) groups, lie on a crystallographic mirror plane. In the crystal, mol-ecules are linked by strong inter-molecular O-H⋯O hydrogen bonds, forming an infinite chain along [100], generating a C(8) motif.


Intraocular pressure spikes after gonioscopy-assisted transluminal trabeculotomy (GATT).
Intraocular pressure (IOP) spikes (IOP > 30 mmHg or > 10 mmHg above baseline IOP) are a common and worrisome complication of gonioscopy-assisted transluminal trabeculotomy (GATT). The purpose of this study is to identify risk factors for IOP spikes and to describe their characteristics, management, and clinical course in a large cohort of patients. A retrospective, single-center study which included 217 consecutive eyes of patients that underwent GATT between December 2019 and April 2022 with follow-up of at least 90 days. IOP spikes occurred in 52 of 217 (24%) eyes. Spikes occurred in 15.5% of patients in whom pre-operative IOP-lowering medications were continued after surgery (90 eyes), and in 29.9% in whom IOP-lowering medications were stopped after surgery (127 eyes). Spikes were diagnosed at a mean of 7.7 ± 6.5 days after surgery. All IOP spikes occurred within the first month of surgery. The mean duration of a spike was 4.9 ± 5.4 days. Management of IOP spikes included adding a mean of 3.13 ± 1.7 groups of glaucoma medications. Thirty-seven (72.5%) eyes were treated with oral carbonic anhydrase inhibitor, 11 (21.6%) were treated with IV mannitol, and anterior chamber paracentesis was performed in 16 (31.4%). Six (11.8%) eyes underwent additional glaucoma surgery to control IOP. Patients that continued their pre-operative IOP-lowering medications after surgery were 2.3 times less likely to develop a spike as compared to patients who discontinued their medications (P = 0.016). Spikes were found to be a risk factor for failure of GATT. IOP spikes are a common occurrence after GATT. They most commonly appear during the first two post-operative weeks and usually resolve with topical and systemic IOP-lowering treatment. The continuation of IOP-lowering medications after GATT is recommended to lower the risk of IOP spikes.


Probing metal ion substrate-binding to the E. coli ZitB exporter in native membranes by solid state NMR.
Metal ion homeostasis is important for healthy cell function and is regulated by metal ion transporters and chaperones. To explore metal ion binding to membrane transport proteins we have used cadmium-113 as a solid state NMR probe of the Escherichia coli zinc exporter ZitB present in native membrane preparations. Competition experiments with other metal ions indicated that nickel and copper are also able to bind to this protein. Metal ion uptake studies were also performed using ZitB-reconstituted into proteoliposomes for a well established fluorescence assay. The results of both the solid state NMR and the uptake studies demonstrate that ZitB is potentially capable of transporting not only zinc but also cadmium, nickel and copper. The solid state NMR approach therefore offers great potential for defining the substrate spectrum of metal ion transporter proteins in their native membrane environments. Further, it should be useful for functional dissection of transporter mechanisms by facilitating the identification of functional residues by mutational studies.


Poultry health constraints in smallholder village poultry systems in Northern Ghana and Central Tanzania.
Smallholder poultry production is a major contributor to food security and rural livelihoods in low-and middle-income countries. However, infectious diseases limit improvements to smallholder poultry production and performance of the sector in general. Infectious diseases of poultry, especially viral diseases, have major impacts on the health and productivity of flocks and account for significant morbidities and mortalities of birds each year. This study utilized participatory epidemiology approaches to better understand the poultry health constraints and challenges faced by smallholder poultry producers in village poultry systems in Northern Ghana and Central Tanzania. The results show dominance of small-scale semi-intensive and extensive scavenging poultry production systems in the study areas. Newcastle disease ranked as the highest cause of morbidity and mortality in chickens in the two countries. The disease occurred mainly during the months coinciding with the dry season in both countries. Other health challenges among poultry flocks included worm infestation, fowl pox, coryza, and coccidiosis. Producers, especially in rural locations, had poor access to veterinary services and critical inputs necessary for poultry production. In the Northern region of Ghana, producers lacked definitive diagnoses for sick poultry due to a shortage of veterinary personnel and diagnostic laboratories. These challenges point to the need for increased investment in poultry disease control and prevention programs, particularly in rural areas. Interventions focused on expansion of veterinary and agricultural extension services and diagnostic laboratory capacity in rural areas and increased gender-sensitive training to enhance smallholder knowledge in poultry husbandry and disease prevention measures will support the development of the smallholder village poultry systems. Tapping into the diverse genetic reservoir of local chicken ecotypes with enhanced resistance to Newcastle disease through genomic selection, coupled with models for enhancing ND vaccination supply and use in the rural areas are potential future avenues for addressing ND constraints to production.


Synthesis of Ti Complexes Supported by an ortho-terphenoxide Ligand and their Applications in Alkyne Hydroamination Catalysis.
The synthesis of a series of Ti complexes of an aryl-linked bis-phenoxide ligand, 3,3''-di-tert-butyl-5,5''-dimethyl-[1,1':2',1''-terphenyl]-2,2''-bis(olate), (TPO)H2, is reported. This ortho-linked terphenyl ligand builds on previously reported meta- and para- linked terphenyl based ligands, completing the isomeric series of terphenoxide ligands. The 4-coordinate (TPO)Ti(NMe2)2 is an active catalyst for alkyne hydroamination with a variety of arylamines, revealing good regioselectivity in reactions with unsymmetric alkynes. Terminal alkynes such as phenylacetylene undergo additional insertion reactions with the key azatitanacyclobutene intermediates, providing further evidence that Ti aryloxide complexes are susceptible to this further reactivity.


Comparison of neurothermography and contrast myelography.
Eighty consecutive patients who first had an electronic infrared thermogram (neurothermogram) and a subsequent oil myelogram were studied retrospectively. All patients had cervical and/or lumbosacral radiculopathy for 90 days. Negative neurothermograms were predictive of negative myelograms in 93% of our series. Positive neurothermograms were predictive of positive myelograms in 71% of the patients. The neurothermogram is not a specific test for intraspinal axis lesions as a cause of radiculopathy. Proximal neuropathic lesions of other causes will also produce abnormalities of the sympathetic autonomic (peripheral) nervous system. The major pathophysiologic findings detected by neurothermograms are complimentary to the EMG, NCVS, and late response techniques. Neurothermography was successful in predicting the outcome of myelography in 82% of patients in this study.


Nonlinear wave-packet interferometry and molecular state reconstruction in a vibrating and rotating diatomic molecule.
We formulate two-color nonlinear wave-packet interferometry (WPI) for application to a diatomic molecule in the gas phase and show that this form of heterodyne-detected multidimensional electronic spectroscopy will permit the reconstruction of photoinduced rovibrational wave packets from experimental data. Using two phase-locked pulse pairs, each resonant with a different electronic transition, nonlinear WPI detects the quadrilinear interference contributions to the population of an excited electronic state. Combining measurements taken with different phase-locking angles isolates various quadrilinear interference terms. One such term gives the complex overlap between a propagated one-pulse target wave packet and a variable three-pulse reference wave packet. The two-dimensional interferogram in the time domain specifies the complex-valued overlap of the given target state with a collection of variable reference states. An inversion procedure based on singular-value decomposition enables reconstruction of the target wave packet from the interferogram without prior detailed characterization of the nuclear Hamiltonian under which the target propagates. With numerically calculated nonlinear WPI signals subject to Gaussian noise, we demonstrate the reconstruction of a rovibrational wave packet launched from the A state and propagated in the E state of Li2.


The role of expression and race in weapons identification.
Emotional expressions can signal intentions and so possess the power to moderate social inferences. Here, we test whether stereotypes implicitly elicited by a stigmatized racial outgroup member are moderated by facial expression. Participants classified pictures of guns and tools that were primed with pictures of Black and White male faces posing angry, happy, and neutral expressions. Across the 3 measures examined--response latencies, error rates, and automatic processing, facial expression modulated implicit stereotyping (Study 1, n = 71; Study 2, n = 166). A Black angry prime elicited implicit stereotyping, while a Black happy prime diminished implicit stereotyping. Responding after neutral primes varied as a function of the expression context. When viewed alongside more threatening expressions (Study 1), neutral Black targets no longer elicited implicit stereotyping, but when viewed alongside more threatening expressions (Study 2), neutral Black targets primed crime and danger-relevant stereotypes. These results demonstrate that an individual can activate different associations based on changes in emotional expression and that a feature present in many everyday encounters (a smile) attenuates implicit racial stereotyping.


Analysis of the variability of S-fimbriae expression in an Escherichia coli pathogen.
The uropathogenic Escherichia coli wild-type strain 536 produces S-fimbriae, P-related fimbriae and type I fimbriae. Using immuno-colony dot and ELISA techniques, variants were detected showing an increased degree of S-fimbrial production. It was demonstrated by immunofluorescence microscopy that in normal (wild-type) and hyper-S-fimbriated E. coli populations non-fimbriated cells also exist, and that the percentage of S-fimbriated and non-fimbriated bacteria was roughly identical in either population. Hyper-S-fimbriated variants could be stably maintained. The transition from wild-type to hyper-S-fimbriation, which occurs spontaneously, is markedly higher than vice versa. Southern blot analysis of the S fimbrial adhesin (sfa) determinants of normal and hyper-fimbriated strains revealed no marked difference in the gene structure.


Liver tumors distinguished by immunofluorescence microscopy with antibodies to proteins of intermediate-sized filaments.
Antibodies against constitutive proteins of different types of intermediate-sized filaments were used in immunofluorescence microscopy on frozen sections of normal rat liver and various rat liver tumors induced by treatment with nitrosamines. Antibodies to tonofilament prekeratin stained bile duct epithelia and hepatocytes of normal liver and hepatocellular carcinoma cells and ductal cells of cholangiofibromas. These cells were not significantly stained by antibodies to vimentin. By contrast, antibodies to vimentin stained mesenchymal cells of normal liver and cells of early and advanced angiosarcomas and of undifferentiated spindle cell sarcoma. These mesenchymal tumor cells were not stained with antibodies to prekeratin. The presence of intermediate-sized filaments in these tumors, often in large whorl-like aggregates, was also demonstrated by electron microscopy. The results show that immunofluorescence microscopy with antibodies to cytoskeletal proteins is a powerful tool for the classification and differential diagnosis of mesenchymal and epithelial liver tumors. We propose that staining with antibodies to proteins of different types of intermediate filaments can be used to improve the identification of tumors of other organs, including metastases, as well as non-neoplastic proliferative lesions.


Hypophosphatemia is Prevalent among Preterm Infants Less than 1,500 Grams.
This article identifies the prevalence and associated factors of hypophosphatemia (HP) in very low birth weight (VLBW) infants in the first week of life. Prospective exploratory cohort study of 106 consecutive VLBW infants admitted to neonatal intensive care at Foothills Hospital, Calgary, Canada. HP was defined as at least one measurement of serum phosphate < 1.5 mmol/L (4.5 mg/dL). Seventy-seven percent (82/106) of the VLBW infants had HP, with significantly higher prevalence in infants < 1,000 g (94%) compared to infants ≥ 1,000 g (61%) (p < 0.001). Hypophosphatemic infants had lower birth weight (p < 0.001), gestational age (p < 0.001), and their increase in phosphate intake was slower (p = 0.003). Respiratory distress syndrome (RDS) (p = 0.002), intraventricular hemorrhage (IVH) ≥ grade III (p = 0.020), and hyperglycemia (p = 0.013) were more frequent among hypophosphatemic infants, especially among those < 1,000 g. Mortality, seizures, arrhythmias, and need for transfusion were not different between groups. Birth weight modified the association between RDS, IVH, hyperglycemia, and HP. HP was ubiquitous among infants < 1,000 g and highly prevalent among those weighing 1,000 to 1,500 g. While the direction of effect was not clear, RDS, IVH, and hyperglycemia were associated with HP. Prevention of HP in these physiologically immature neonates might improve neonatal outcomes.


[Tension-force induced cyclooxygenase-2 expression mediated by microfilament in human periodontal ligament fibroblast].
To study the role of microfilament polymerization in menchanotransduction by human periodontal ligament fibroblast (hPDLFs). In tension-force group, hPDLFs were treated by tension-force values of 18% for 8 h, 16 h, 24 h. In tension-force and inhibitor group, the sample was treated with 5 microg/mL cytochalasin B before using tension-forece. Each sample was collected and the expression of cyclooxygenase-2 was measured by using immunohistoche staining. In tension-force group, the expression of cyclooxygenase-2 enhanced with the extension of loading time. In tension-force and inhibitor group, cyclooxygenase-2 expression was depressed and had no relation with loading time. Tension-force induced cyclooxygenase-2 expression is mediated by microfilament, disruption of the microfilament polymerization will destroy mechanotransduction in hPDLFs.


Lung cancer risks of underground miners: cohort and case-control studies.
All underground mines have higher radon levels than are found in surface air. Ventilation is the primary method of controlling radon levels. Fourteen cohort and seven case-control studies done on underground miners are reviewed; they include many types of ore. Only five of the studies deal with more than 100 lung cancer deaths. Variations in the attributable risk are given. Some generalizations can be drawn from these studies: the longer the follow-up, the greater is the attributable risk, even though the relative risk is reasonably constant. The induction-latent period is quite variable but is shortened by high exposure rates, by cigarette smoking, and by increasing age at start of mining. The predominant histological type of lung cancer among miners changed from small-cell undifferentiated for short follow-up time to epidermoid after long follow-up times. With short follow-up time, a multiplicative interaction between smoking and radiation was indicated, but, with long follow-up time, the two factors appear to be simply additive. This difference is probably due to the shortened latent period among cigarette smokers, not to synergism.


Disease-specific quality of life in young patients with tourette syndrome.
Tourette syndrome is a neurodevelopmental disorder characterized by multiple tics and is often associated with comorbid behavioral problems. Research with generic instruments in child populations showed that comorbid disorders can have a greater impact on health-related quality of life than tic severity. This study investigated the usefulness of a newly developed disease-specific instrument, the Gilles de la Tourette Syndrome-Quality of Life Scale for Children and Adolescents (GTS-QOL-C&A), in assessing health-related quality of life in young patients with Tourette syndrome with and without behavioral comorbidity. We recruited 75 patients with Tourette syndrome (60 males; age 12.4 ± 3.2 years). All participants were evaluated by a neuropsychiatrist and completed a standardized psychometric battery, including the GTS-QOL-C&A, Child Depression Inventory, and Multidimensional Anxiety Scale for Children. Forty-two patients (56%) fulfilled diagnostic criteria for at least one comorbidity: obsessive-compulsive disorder (n = 25 patients [33.3%]); attention deficit/hyperactivity disorder (n = 6 patients [8%]); both (n = 11 patients [14.7%]). The GTS-QOL-C&A demonstrated usefulness in differentiating "pure" Tourette syndrome from Tourette syndrome "plus" behavioral problems with regard to health-related quality of life scores for the obsessive-compulsive subscale. In addition to focusing on core tic symptoms, the GTS-QOL-C&A showed sensitivity to the impact of behavioral comorbidities on health-related quality of life and can usefully complement existing nonspecific instruments.


Assessing the validity of a single-item HIV risk stage-of-change measure.
This study examined the validity of a single-item measure of HIV risk stage of change that HIV prevention contractors were required to collect by the California State Office of AIDS. The single-item measure was compared to the more conventional University of Rhode Island Change Assessment (URICA). Participants were members of Los Angeles County-defined behavioral risk groups recruited from a mobile HIV testing program (N = 123). The study found low correspondence between participants' stage of change on the single-item and the URICA, suggesting that they do not assess the same construct, and that the single item may not provide a valid measure. The current data suggests that the single-item measure should be revised or abandoned in favor of more conventional stage-of-change measures.


The comparative genomics of T-box genes.
T-box genes are defined by the presence of a conserved sequence, the so-called T-box; this codes for the T-domain, which is involved in DNA-binding and protein dimerisation. Members of this gene family have been found in all metazoans, from diploblasts to humans, and mutations in T-box gene family members in humans have been linked to several congenital disorders. Sequencing of the complete genomes of a range of invertebrate and vertebrate species has allowed the classification of individual T-box genes into five subfamilies: Brachyury, T-brain1, Tbx1, Tbx2 and Tbx6. This review will largely focus on T-box genes identified in organisms whose genomes have been fully sequenced, emphasising how comparative studies of the T-box gene family will help to reveal the roles of these genes during development and in the adult.


A new method for measuring inhibition of platelet function by nonsteroidal antiinflammatory drugs.
Aspirin is widely used to help prevent vascular occlusion caused by atherosclerotic vascular disease. We used a platelet-aggregation assay (PAA) to evaluate the reliability of a proprietary platelet agonist, platelet prostaglandin agonist (PPA), to detect the amount of platelet inhibition induced by four different classes of nonsteroidal antiinflammatory drugs (NSAIDs) with antiplatelet effects. Twenty normal donors were evaluated before and 24 hours after ingestion of 325 mg of aspirin. With 125 micromol/L PPA, the slope of the PPA-PAA curve completely differentiated aspirin-treated from normal platelets. The aspirin platelet slope, 27.9 +/- 2.0 (range 5.5-47), was significantly decreased (P <.001) compared with the findings before administration of aspirin, 75 +/- 3.1 (range 50-125). Additionally, the time elapsed before 50% platelet aggregation (T(50)) with aspirin, 10.1 +/- 0.7 minutes (range 4.7-17), was significantly prolonged (P <.05) compared with the mean time before administration of aspirin (4.2 +/- 0.2 minutes, range 1.7-6.4). Aspirin in a daily dosage of 325 mg for 14 days produced significantly greater inhibition of PPA-PAA than that induced by a single 325-mg dose (P <.001). The long-term platelet-inhibitory effects of aspirin in 9 normal volunteers were evaluated with PPA-PAA 2, 8, 24, 48, 72, and 96 hours after a single dose of aspirin, 81 or 325 mg. Compared with the preaspirin slope, 79.6 +/- 1.9, the maximal decrease in slope occurred after 2 hours for both 81 mg (61.3 +/- 6.7) and 325 mg (12.1 +/- 1.8). The decreased slopes and increased T(50) observed at 2, 8, and 24 hours (P <.001) reflected the greater degree of platelet inhibition with 325 mg than with 81 mg aspirin. Inhibition of PPA-PAA was observed with nonaspirin nonsteroidal antiinflammatory drugs (NNSAIDs), but, compared with aspirin, the inhibition was minimal. PPA-PAA may be used to help measure the magnitude of NSAID-induced inhibition of platelets.


Hydrothermal Synthesis of Pyrochlore-Type Pentavalent Bismuthates Ca2Bi2O7 and Sr2Bi2O7.
The pyrochlore-type Ca2Bi2O7 and Sr2Bi2O7 have been synthesized from a low-temperature hydrothermal route using NaBiO3·nH2O as a starting material. The crystal structures of these compounds were refined using synchrotron powder X-ray diffraction data. The cell parameters were found to be a = 10.75021 (5) Å and 10.94132 (6) Å for Ca2Bi2O7 and Sr2Bi2O7, respectively. Density functional theory calculations showed the metallic band structure, but the negligible mixing of O2 2p bands with the A-site alkaline-earth-metal states and weak overlap with the conduction bands result in the semiconducting behavior.


Pediatrician characteristics associated with attention to spirituality and religion in clinical practice.
The literature suggests that a majority of pediatricians believe that spirituality and religion are relevant in clinical practice, but only a minority gives them attention. This project explored this disparity by relating personal/professional characteristics of pediatricians to the frequency with which they give attention to spirituality and religion. Pediatricians (N = 737) associated with 3 academic Midwestern pediatric hospitals responded to a survey that requested information concerning the frequency with which they (1) talked with patients/families about their spiritual and religious concerns and (2) participated with them in spiritual or religious practices (eg, prayer). The associations between these data and 10 personal and professional characteristics were examined. The results demonstrated the disparity, and the analysis identified 9 pediatrician characteristics that were significantly associated with more frequently talking with patients/families about their spiritual and religious concerns. The characteristics included increased age; a Christian religious heritage; self-description as religious; self-description as spiritual; the importance of one's own spirituality and religion in clinical practice; the belief that the spirituality and religion of patients/families are relevant in clinical practice; formal instruction concerning the role of spirituality and religion in health care; relative comfort asking about beliefs; and relative comfort asking about practices. All of these characteristics except pediatrician age were also significantly associated with the increased frequency of participation in spiritual and religious practices with patients/families. Attention to spiritual and religious concerns and practices are associated with a web of personal and professional pediatrician characteristics. Some characteristics pertain to the physician's personal investment in spirituality and religion in their own lives, and others include being uncomfortable with spiritual and religious concerns and practices. These associations shed light on the disparity between acknowledged spirituality and religion relevancy and inattention to it in clinical practice.


Ghrelin suppresses insulin secretion in human islets and type 2 diabetes patients have diminished islet ghrelin cell number and lower plasma ghrelin levels.
It is not known how ghrelin affects insulin secretion in human islets from patients with type 2 diabetes (T2D) or whether islet ghrelin expression or circulating ghrelin levels are altered in T2D. Here we sought out to identify the effect of ghrelin on insulin secretion in human islets and the impact of T2D on circulating ghrelin levels and on islet ghrelin cells. The effect of ghrelin on insulin secretion was assessed in human T2D and non-T2D islets. Ghrelin expression was assessed with RNA-sequencing (n = 191) and immunohistochemistry (n = 21). Plasma ghrelin was measured with ELISA in 40 T2D and 40 non-T2D subjects. Ghrelin exerted a glucose-dependent insulin-suppressing effect in islets from both T2D and non-T2D donors. Compared with non-T2D donors, T2D donors had reduced ghrelin mRNA expression and 75% less islet ghrelin cells, and ghrelin mRNA expression correlated negatively with HbA1c. T2D subjects had 25% lower fasting plasma ghrelin levels than matched controls. Thus, ghrelin has direct insulin-suppressing effects in human islets and T2D patients have lower fasting ghrelin levels, likely as a result of reduced number of islet ghrelin cells. These findings support inhibition of ghrelin signaling as a potential therapeutic avenue for stimulation of insulin secretion in T2D patients.


Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer.
Group 3 innate lymphoid cells (ILC3s) regulate immunity and inflammation, yet their role in cancer remains elusive. Here, we identify that colorectal cancer (CRC) manifests with altered ILC3s that are characterized by reduced frequencies, increased plasticity, and an imbalance with T cells. We evaluated the consequences of these changes in mice and determined that a dialog between ILC3s and T cells via major histocompatibility complex class II (MHCII) is necessary to support colonization with microbiota that subsequently induce type-1 immunity in the intestine and tumor microenvironment. As a result, mice lacking ILC3-specific MHCII develop invasive CRC and resistance to anti-PD-1 immunotherapy. Finally, humans with dysregulated intestinal ILC3s harbor microbiota that fail to induce type-1 immunity and immunotherapy responsiveness when transferred to mice. Collectively, these data define a protective role for ILC3s in cancer and indicate that their inherent disruption in CRC drives dysfunctional adaptive immunity, tumor progression, and immunotherapy resistance.


A Novel Rat Model of Nonalcoholic Fatty Liver Disease Constructed Through CRISPR/Cas-Based Hydrodynamic Injection.
CRISPR/Cas technology has been widely used in generating conventional and conditional gene knockout animals through germline mutation. A recent study has demonstrated that CRISPR/Cas system also worked on nongermline mutation in mice liver via hydrodynamic injection of vector plasmid to blood circulation. However, whether this is also applied to rat and what is the optimal concentration of vector plasmid still need to be studied. Here, we attempted to use pX330-Pten plasmid to knock down the expression of Pten in rat liver for generation of nonalcoholic fatty liver disease (NAFLD) rat model. A range of pX330-Pten dosages (75, 150 and 300 μg/100 g) in 10 ml of saline water was injected into the blood circulation of SD rats within 30 s by tail vein injection. The data showed that, 9 weeks after injection, no differences of TC, AST and ALT were found between control and the treatment groups (low-dose, mid-dose, high-dose and fat-diet groups). However, the high-dose group revealed severe lipid deposition and significant knockdown of Pten, which was validated by western blot and real-time PCR. Notably, lipid deposition and Pten knockdown were detected in the liver of animals from the high-dose group as early as 6 weeks after injection. Taken together, our findings demonstrated that hydrodynamic injection of pX330-Pten plasmid at the dosage of 300 μg/100 g can knock down the expression of Pten in rat liver efficiently, resulting in lipid deposition as well as NAFLD. Taken together, this study presents a novel and efficient method to edit genome in rat liver.


[The multifunctionality of regulatory peptides and the rule of "what--where--when" as a principle of their ordered action].
Consistent study of stages and history of discovery of regulatory peptides (RP) as a new class of multifunctional endogenic regulators puts forward some actual problems. A question what new notions on the manner of control of physiological functions have been introduced by RP investigation is considered. Two historical tendencies in the RP studies are estimated. A conception on peptides as multifunctional and colocated factors of neurohumoral regulation of organism was opposed to the idea of "single" substance--a regulator of "unique" function. In this connection a conception of peptide-regulatory continuum is considered and the author postulated the principle "what--where--when" as the main rule of RP well-regulated action. The statement on tissue (regional) specificity of the biogenesis processes of different RP as molecular basis of their regulatory function is grounded.


Cellular micromotion monitored by long-range surface plasmon resonance with optical fluctuation analysis.
Long-range surface plasmon resonance (LRSPR) is a powerful biosensing technology due to a substantially larger probing depth into the medium and sensitivity, compared with conventional SPR. We demonstrate here that LRSPR can provide sensitive noninvasive measurement of the dynamic fluctuation of adherent cells, often referred to as the cellular micromotion. Proof of concept was achieved using confluent layers of 3T3 fibroblast cells and MDA-MB-231 cancer cells. The slope of the power spectral density (PSD) of the optical fluctuations was calculated to determine the micromotion index, and significant differences were measured between live and fixed cell layers. Furthermore, the performances of LRSPR and conventional surface plasmon resonance (cSPR) were compared with respect to micromotion monitoring. Our study showed that the micromotion index of cells measured by LRSPR sensors was higher than when measured with cSPR, suggesting a higher sensitivity of LRSPR to the micromotion of cells. To investigate further this finding, simulations were conducted to establish the relative sensitivities of LRSPR and cSPR to membrane fluctuations. Increased signal intensity was predicted for LRSPR in comparison to cSPR, suggesting that membrane fluctuations play a significant role in the optical micromotion measured in LRSPR. Analogous to cellular micromotion measured using impedance techniques, LRSPR micromotion has the potential to provide important biological information on the metabolic activity and viability of adherent cells.


Dynamic modeling of immobilized cell reactor: application to ethanol fermentation.
A mathematical model has been developed for the unsteady-state operation of an immobilized cell reactor. The substrate solution flows through a mixed-flow reactor in which cells immobilized in gel beads are retained. The substrate diffuses from the external surface of the gel beads to some internal location where reaction occurs. The product diffuses from the gel beads into liquid medium which flows out of the reactor. The model combines simultaneous diffusion and reaction, as well as cell growth, and it can predict how the rates of substrate consumption, product formation, and cell growth vary with time and with initial conditions. Ethanol fermentation was chosen as a representative reaction in the immobilized cell reactor, and numerical calculations were carried out. Excellent agreement was observed between model predictions and experimental data available in the literature.


Prevention and suppression of autoimmune encephalomyelitis by EUK-8, a synthetic catalytic scavenger of oxygen-reactive metabolites.
Breakdown of T cell tolerance to self-myelin basic protein induces an autoimmune process that leads to demyelination of the central nervous system (CNS) in multiple sclerosis (MS) patients. While the autoimmune disease is initiated by antigen-specific autoreactive T cells, there is accumulating evidence that CNS injury is essentially mediated by CNS-infiltrating inflammatory cells. In addition, it is established that activated macrophages and polymorphonuclear cells contribute to tissue damage in several inflammatory diseases by releasing highly reactive oxygen metabolites. It was therefore possible that demyelination associated with MS results from oxidative injury caused by a cascade of oxygen reactive metabolites produced by CNS-infiltrating activated macrophages and other inflammatory cells. To address this question, we tested the effect of a synthetic catalytic scavenger of oxygen radicals, EUK-8, on experimental allergic encephalomyelitis (EAE) in mice, the animal model for MS in humans. We observed that repeated injection of EUK-8 starting at the time of EAE induction delayed the onset and markedly reduced the severity of the disease. Strikingly, all EUK-8-treated mice completely recovered after 40 days. In addition, we showed that posttreatment with EUK-8 4 days after EAE induction also resulted in a significant amelioration of EAE disease. These results indicate that oxygen metabolites secreted by inflammatory cells at the site of tissue destruction play a major role in the induction and presumably the perpetuation of the autoimmune disease. This study also suggests that treatment with oxygen metabolites scavengers may represent a novel and promising strategy to prevent the onset and to block the course of ongoing autoimmune encephalomyelitis and other inflammatory autoimmune diseases.


Safety and Precision of Two Different Flap-morphologies Created During Low Energy Femtosecond Laser-assisted LASIK.
Currently, two major principles exist to create LASIK flaps: firstly, a strictly horizontal (2D) cut similar to the microkeratome-cut and secondly an angled cut with a "step-like" edge (3D). The strictly horizontal (2D) cut method can be performed using apparatus such as the low-energy FEMTO LDV Z8 laser and its predecessors which are specific to this type. Alternatively, the low-energy FEMTO LDV Z8 laser's 3D flap design creates an interlocking flap-interface surface which potentially contributes toward flap stability. In addition, the FEMTO LDV Z8 offers flap-position adjustments after docking (before flap-creation). The current study analyzed precision, safety, efficacy, as well as patient self-reported pain and comfort levels after applying two different types of LASIK flap morphologies which were created with a low-energy, high-frequency femtosecond (fs) laser device. A prospective, interventional, randomized, contralateral eye, single-center comparison study was conducted from November 2019 to March 2020 at the Hamburg vision clinic/ zentrumsehstärke, Hamburg, Germany. Eleven patients and 22 eyes received low-energy fs LASIK treatment for myopia or myopic astigmatism in both eyes. Before the treatment, the eyes were randomized (one eye was treated with the 2D, the other eye with the 3D method). The mean central flap thickness one month after surgery was 110.7 ± 1.6 μm (2D) and 111.2 ± 1.7 μm (3D); P = 0.365 (2D vs 3D). Flap thickness measured at 13 different points resulted in no statistically significant differences between any of the measurement points within/between both groups; demonstrating good planarity of the flap was achieved using both methods. Despite not being statistically significant, the surgeons recognized an increase in the presence of an opaque bubble layer in the 3D flap eyes during surgery and some patients reported higher, yet not statistically significant, pain scores in the 3D flap eyes during the first hours after the treatment. Overall, safety- and efficacy indices were 1.03 and 1.03, respectively. In this prospective, randomized, contralateral eye study, the low-energy fs laser yielded predictable lamellar flap thicknesses and geometry at one-month follow-up. Based on these results, efficacy and safety of the corresponding laser application, that is, 2D vs 3D, are equivalent.


Formation of surface nanodroplets of viscous liquids by solvent exchange.
Surface nanodroplets are essential units for many compartmentalised processes from catalysis, liquid-liquid reactions, crystallization, wetting and more. Current techniques for producing submicron droplets are mainly based on top-down approaches, which are increasingly limited as scale reduces. Herein, solvent exchange is demonstrated as a simple solution-based approach for the formation of surface nanodroplets with intermediate and extremely high viscosity (1 000 000 cSt). By solvent exchange, the viscous droplet liquid dissolves in a good solvent that is then displaced by a poor solvent to yield surface droplets for the oversaturaion pulse at the mixing front. Within controlled flow conditions, the geometry of droplets of low and intermediate viscosity liquids can be tailored on the nano and microscale by controlling the flow rate. Meanwhile for extremely viscous liquids, the droplet size is shown to be dependent on the liquid temperature. This work demonstrates that solvent exchange offers a versatile tool for the formation of droplets with a wide range of viscosity.


Promoting colorectal cancer screening through group education in community-based settings.
National colonoscopy adherence rates near 65% and New York City (NYC) colonoscopy rates approach 69%. Despite an overall increase in national colorectal cancer (CRC) screening rates, rates of CRC screening among Blacks and Latinos are lower than non-Latino Whites. We developed two group level, culturally targeted educational programs about CRC for Blacks and Latinos. One hour programs included education about screening, peer testimony given by a colonoscopy-adherent person, and pre- and post-knowledge assessment. From 2010 to 2012, we conducted 66 education programs in NYC, reaching 1,065 participants, 62.7% of whom were 50 years of age or older identified as Black or Latino and provided information about colonoscopy history (N = 668). Colonoscopy adherence in the sample was 69.3%. There was a significant increase in mean knowledge score about CRC and CRC screening from pretest to posttest. Sixty-eight percent of attendees without prior colonoscopy reported intent to schedule a colonoscopy as a result of attending the program. Culturally targeted education programs with peer testimony are a valuable way to raise awareness about CRC and colonoscopy and can influence intent to screen among nonadherent persons. Additional research is needed to establish group level education as an effective means of promoting CRC screening.


Progress on antiangiogenic therapy for patients with malignant glioma.
Glioblastoma (GBM) is the most common primary brain tumor occurring in America. Despite recent advances in therapeutics, the prognosis for patients with newly diagnosed GBM remains dismal. As these tumors characteristically show evidence of angiogenesis (neovascularization) there has been great interest in developing anti-angiogenic therapeutic strategies for the treatment of patients with this disease and some anti-angiogenic agents have now been used for the treatment of patients with malignant glioma tumors. Although the results of these clinical trials are promising in that they indicate an initial therapeutic response, the anti-angiogenic therapies tested to date have not changed the overall survival of patients with malignant glioma tumors. This is due, in large part, to the development of resistance to these therapies. Ongoing research into key features of the neovasculature in malignant glioma tumors, as well as the general angiogenesis process, is suggesting additional molecules that may be targeted and an improved response when both the neovasculature and the tumor cells are targeted. Prevention of the development of resistance may require the development of anti-angiogenic strategies that induce apoptosis or cell death of the neovasculature, as well as an improved understanding of the potential roles of circulating endothelial progenitor cells and vascular co-option by tumor cells, in the development of resistance.


Methodological approach for assessing the cost-effectiveness of treatments using longitudinal observational data: the SOHO study.
The objective of this study was to develop a method to allocate treatment effects when patients switch medication frequently in longitudinal observational studies and apply the approach to assess the cost-effectiveness of treatments in the Schizophrenia Outpatient Health Outcomes (SOHO) study. Data were collected on patients at entry to the SOHO study at 3, 6, and 12 months. The 12-month follow-up period was considered as three epochs: 0-3 months, 3-6 months, and 6-12 months. Patients who switched treatment at 3 months had their new treatment considered as a new baseline observation, as these two 3-month observations provide two sets of information on the cost-effectiveness of a drug in the first 3 months after initiation. Multivariate regression analysis was used to adjust for baseline covariates. The model allowed for flexible functional forms, and the cost data were modeled using an exponential mean function. Bootstrapping assessed the uncertainty of the estimated parameters and incremental cost-effectiveness analysis decision rule. We show the feasibility of the epoch analysis approach using data from the SOHO study comparing two antipsychotics. Estimates for the incremental cost and effectiveness per epoch over the full 12-month period are presented. Using the estimates of 200 bootstrap samples, we demonstrate how one drug is cost-effective compared with another.


Mechanisms responsible for the sustained fall in arterial oxygen tension after endotracheal suctioning in dogs.
Because a sustained fall in arterial oxygen tension (PaO2) was observed after endotracheal suctioning in previous studies on anesthetized dogs and in humans, this study was designed to investigate the nature of the fall, its duration, and its response to several challenges. Experiments were performed at weekly intervals using three anesthetized dogs. Each dog was subjected to five experiments. In spontaneously breathing dogs, the duration of the sustained fall after suctioning or after suction catheter insertion without application of suction pressure persisted through 15 minutes. At 30 minutes afterwards, PaO2 had partially or completely returned to control levels. One hyperinflation breath given after suctioning did not produce a lasting reversal of the sustained fall, and pretreatment with isoproterenol mist inhalations failed to prevent the sustained fall. In dogs which were mechanically ventilated both before and after suctioning or catheter insertion without application of suction pressure, three hyperinflations before suctioning or pretreatment with isoproterenol failed to prevent the sustained fall. The data supported the hypothesis that a reflex mechanism, initiated by mechanical stimulation of the airways, was responsible for the sustained fall in PaO2 observed.


An overview of natural renewable bio-polymer lignin towards nano and biotechnological applications.
Lignin were said to be major bio-polymer next to cellulose which is an abundant biopolymer. This type of lignin was mostly isolated from woods which were named after their physical, morphological appearances and majorly on extracting sources. Still now there are very few reports on isolation, identification of pure lignin and isolating pathways are also not well defined. Molecular weight of lignin varies from thousands to ten thousands which are not explored accurately. Even-though lignins were surrounded by these many hurdles it has various application studies which were studied and reported. Nowadays researchers focused on synthesizing lignin nanoparticles which were subjected for various application studies in day today life. This lignin contains wide range of applications in several fields like medicinal, industrial, pharmaceuticals, etc., Most of the researcher are focused on applications like anti-oxidant and microbicidal agents. So this review will comprises of outlook of bioprocessing lignin and its application focused on nanoparticles synthesis, anti-oxidant and microbicidal agents. This was the first review on renewable bio-polymer lignin with its bio-pharmaceutical and nanobiotechnological applications.


IS901, a new member of a widespread class of atypical insertion sequences, is associated with pathogenicity in Mycobacterium avium.
An insertion sequence (IS901), found in pathogenic strains of Mycobacterium avium, but absent in M. avium complex isolates from patients with acquired immune deficiency syndrome (AIDS), has been isolated and sequenced. This insertion element has a nucleotide sequence of 1472 bp, with one open reading frame (ORF1), which codes for a protein of 401 amino acids. The amino acid sequence, terminal ends and target site of IS901 are similar to those of IS900, present in Mycobacterium paratuberculosis. However, the DNA sequences of these two IS elements exhibit only 60% homology, compared to a DNA homology of 98% between their respective hosts. IS901, like IS900, appears to belong to a family of related insertion elements present in actinomycetes and other bacteria. M. avium strains containing IS901 were found to be more virulent in mice than closely related strains lacking IS901. IS901 may be a useful tool for the study of the genetics of virulence in the M. avium complex and for obtaining stable integration of foreign genes into mycobacteria.


Association Between METS-IR and Prehypertension or Hypertension Among Normoglycemia Subjects in Japan: A Retrospective Study.
Our study aimed to investigate the association between the novel non-insulin-based metabolic score for insulin resistance (METS-IR) index and pre-hypertension (HTN) or HTN in normoglycemia Japanese participants. The NAGALA medical examination program at Murakami Memorial Hospital in Gifu, Japan was found in 1994. 15,453 participants enrolled in this program from 2004 to 2015 was included in this retrospective study to explore the association between the METS-IR index and pre-HTN or HTN. Covariates included serum biomarkers and clinicodemographic characteristics. Logistic regression was applied to explore the association between METS-IR level and pre-HTN or HTN. This study includes a total of 15453 participants. The prevalence rates of pre-HTN and HTN were 28.55% (4412/15453) and 6.23% (962/15453), respectively. Adjusted for confounding factors in the multivariable logistic regression analysis models, when METS-IR was used as a categorical variable, high METS-IR was significantly associated with both pre-HTN (adjusted odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.61-2.36) and HTN (adjusted OR = 2.12, 95% CI: 1.44-3.11). When METS-IR was used as a continuous variable, each 1 unit increase in METS-IR was associated with a 7% increase in the prevalence of pre-HTN (adjusted OR = 1.07, 95% CI: 1.06-1.08) and with a 13% increase in the prevalence of HTN (adjusted OR = 1.13, 95% CI: 1.10-1.16). Stratified analyses indicated a positive correlation between METS-IR and pre-HTN or HTN in normoglycemia subjects with different characteristics. METS-IR levels are significantly associated with pre-HTN or HTN in normoglycemia individuals in Gifu, Japan. METS-IR may be used as a monitoring indicator for the development of HTN primary prevention and management strategies in the future, but it still needs more research to confirm.


Biogenesis of zinc storage granules in Drosophila melanogaster.
Membrane transporters and sequestration mechanisms concentrate metal ions differentially into discrete subcellular microenvironments for use in protein cofactors, signalling, storage or excretion. Here we identify zinc storage granules as the insect's major zinc reservoir in principal Malpighian tubule epithelial cells of Drosophila melanogaster The concerted action of Adaptor Protein-3, Rab32, HOPS and BLOC complexes as well as of the white-scarlet (ABCG2-like) and ZnT35C (ZnT2/ZnT3/ZnT8-like) transporters is required for zinc storage granule biogenesis. Due to lysosome-related organelle defects caused by mutations in the homologous human genes, patients with Hermansky-Pudlak syndrome may lack zinc granules in beta pancreatic cells, intestinal paneth cells and presynaptic vesicles of hippocampal mossy fibers.


Computational study of C(sp3)-O bond formation at a PdIV centre.
This report describes a computational study of C(sp3)-OR bond formation from PdIV complexes of general structure PdIV(CH2CMe2-o-C6H4-C,C')(F)(OR)(bpy-N,N') (bpy = 2,2'-bipyridine). Dissociation of -OR from the different octahedral PdIV starting materials results in a common square-pyramidal PdIV cation. An SN2-type attack by -OR (-OR = phenoxide, acetate, difluoroacetate, and nitrate) then leads to C(sp3)-OR bond formation. In contrast, when -OR = triflate, concerted C(sp3)-C(sp2) bond-forming reductive elimination takes place, and the calculations indicate this outcome is the result of thermodynamic rather than kinetic control. The energy requirements for the dissociation and SN2 steps with different -OR follow opposing trends. The SN2 transition states exhibit "PdCO" angles in a tight range of 151.5 to 153.0°, resulting from steric interactions between the oxygen atom and the gem-dimethyl group of the ligand. Conformational effects for various OR ligands and isomerisation of the complexes were also examined as components of the solution dynamics in these systems. In all cases, the trends observed computationally agree with those observed experimentally.


Formation of thick, large-area nanoparticle superlattices in lithographically defined geometries.
Superlattices of colloidal nanocrystals hold the promise of new nanomaterials with tunable properties. The positioning and size of these structures are often poorly controlled after self-assembly from the solution phase, making studies of their properties difficult. We report the fabrication of approximately 100 layer thick, three-dimensional superlattices on a substrate with controlled lateral placement. This novel fabrication technique generates long-range order over the micrometer scale and controlled placement by employing lithographic patterning and microfluidic flow.


Optimization of Glutaraldehyde Vapor Treatment for Electrospun Collagen/Silk Tissue Engineering Scaffolds.
Freestanding fibrous matrices with proper protein composition and desirable mechanical properties, stability, and biocompatibility are in high demand for tissue engineering. Electrospun (E-spun) collagen-silk composite fibers are promising tissue engineering scaffolds. However, as-spun fibers are mechanically weak and unstable. In this work, we applied glutaraldehyde (GA) vapor treatment to improve the fiber performance, and the effect on the properties of E-spun collagen-silk fibers was studied systematically. GA treatment was found to affect collagen and silk distinctively. Whereas GA chemically links collagen peptides, it induces conformational transitions to enrich β-sheets in silk. The combined effects impose a control of the mechanical properties, stability, and degradability of the composite fibers, which are dependent on the extent of GA treatment. In addition, a mild treatment of the fibers did not diminish cell proliferation and viability. However, overly treated fibers demonstrated reduced cell-matrix adhesion. The understanding of GA treatment effects on collagen, silk, and the composite fibers enables effective control and fine tuning of the fiber properties to warrant their diverse in vitro and in vivo applications.


Parvalbumin-positive projection neurons characterise the vocal premotor pathway in male, but not female, zebra finches.
Parvalbumin (PV) and calbindin (CB) immunoreactivities were assessed in nucleus robustus archistriatalis (RA) of male and female zebra finches, together with retrograde labelling of RA neurons. The results of double and triple labelling experiments suggested that, in males, moderately and faintly PV-positive neurons were projection neurons, but that all intensely PV-positive cells were not. The latter, which are presumably interneurons, were also intensely CB-positive, and may correspond to the GABAergic inhibitory interneurons identified by others. In addition, the complete RA pathway and its terminal fields in the respiratory-vocal nuclei of the brainstem were strongly PV-positive. In female zebra finches, which do not sing, no evidence was found that PV-positive RA cells were projection neurons, yet the pattern of projections of RA neurons, as determined by anterograde transport of biotinylated dextran amine, was very similar to that of RA in males. Moreover, in females, RA neurons retrogradely labelled from injections of cholera toxin B-chain into the tracheosyringeal nucleus (XIIts) were abundant and included, in the lateral part of the nucleus, a population of cells that were as large as those in the male RA. Parvalbumin immunoreactivity was also present in RA and its projections in males of several other songbird species (northern cardinal, brown headed cowbird, canary) and in the female cardinal, which sings to some extent, but the labelling was not as intense as that in male zebra finches.


Binding and activation of plasminogen at the surface of Staphylococcus aureus. Increase in affinity after conversion to the Lys form of the ligand.
Untreated Staphylococcus aureus cells, strain Cowan I, specifically bound 125I-Glu-plasminogen. The binding was inhibited by both unlabeled Glu-plasminogen and Glu-plasmin. The Lys form of plasminogen, which lacks the 8-kDa amino-terminal activation peptide, was approximately 100-fold more effective than the Glu form in competing with the binding of 125I-labeled Glu-plasminogen. This suggests an increase in binding affinity upon removal of the activation peptide. Fibronectin, fibrinogen and IgG, plasma components known to bind to the staphylococcal surface, did not significantly interfere with the binding. The competing activity in plasma was abolished by specifically absorbing plasminogen from the plasma sample. L-Lysine and a fragment of plasminogen containing three of the first five protein attachment domains present in the molecule (kringle structures) also competed with plasminogen for binding suggesting that the lysine-binding sites of plasminogen were involved in its interaction with staphylococci. Scatchard analysis revealed high- and low-affinity binding sites. Kd and the number of high-affinity binding sites were 1.7 nM and 780 binding sites/bacterial cell, respectively. 125I-Glu-plasminogen bound to staphylococcal surface was converted to plasmin by tissue-type plasminogen activator. The conversion took place also in the presence of plasma. If the conversion was carried out in the absence of low-molecular-mass plasmin inhibitors such as aprotinin, the bound Glu-plasmin was further converted to Lys-plasmin. The surface-bound plasmin was enzymically active, as judged by digestion of the synthetic substrate, S-2251. The plasminogen conversion shown by the present experiments not only leads to the surface-bound plasmin but seems to considerably increase the affinity of plasmin for its binding site. This may represent a physiologically relevant method for a bacterial cell to retain surface-bound active plasmin which is also protected from its soluble plasma inhibitors. This novel mechanism for staphylococci to adopt surface-bound proteolytic activity, without the interference of plasma components, may have some role in the tissue penetration and invasion of microbes during infection.


A PIANO (Proper, Insufficient, Aberrant, and NO Reprogramming) Response to the Yamanaka Factors in the Initial Stages of Human iPSC Reprogramming.
Yamanaka reprogramming is revolutionary but inefficient, slow, and stochastic. The underlying molecular events for these mixed outcomes of induction of pluripotent stem cells (iPSC) reprogramming is still unclear. Previous studies about transcriptional responses to reprogramming overlooked human reprogramming and are compromised by the fact that only a rare population proceeds towards pluripotency, and a significant amount of the collected transcriptional data may not represent the positive reprogramming. We recently developed a concept of reprogramome, which allows one to study the early transcriptional responses to the Yamanaka factors in the perspective of reprogramming legitimacy of a gene response to reprogramming. Using RNA-seq, this study scored 579 genes successfully reprogrammed within 48 h, indicating the potency of the reprogramming factors. This report also tallied 438 genes reprogrammed significantly but insufficiently up to 72 h, indicating a positive drive with some inadequacy of the Yamanaka factors. In addition, 953 member genes within the reprogramome were transcriptionally irresponsive to reprogramming, showing the inability of the reprogramming factors to directly act on these genes. Furthermore, there were 305 genes undergoing six types of aberrant reprogramming: over, wrong, and unwanted upreprogramming or downreprogramming, revealing significant negative impacts of the Yamanaka factors. The mixed findings about the initial transcriptional responses to the reprogramming factors shed new insights into the robustness as well as limitations of the Yamanaka factors.


Noninvasive measurement of traveling wave velocity in the canine larynx.
Laryngologists have long recognized that assessment of the mucosal wave is an important part of laryngeal evaluation. This is the first report of a noninvasive measurement of vocal fold displacement velocity in an in vivo canine model. A newly developed calibrating endoscopic instrument capable of measuring distances on the vocal fold surface is described. Displacement velocity was determined in three dogs and compared to physiologic measures in the in vivo phonation model. The results indicate that the calculated displacement velocity is linearly proportional to traveling wave velocity and fundamental frequency. Because traveling wave velocity has been shown to reflect vocal fold stiffness, this method may advance the usefulness of stroboscopy for the study of mucosal wave abnormalities.


Rates of autism and potential risk factors in children with congenital heart defects.
Atypical development, behavioral difficulties, and academic underachievement are common morbidities in children with a history of congenital heart defects and impact quality of life. Language and social-cognitive deficits have been described, which are associated with autism spectrum disorders. The current study aimed to assess the rates of autism spectrum disorders in a large sample of children with a history of congenital heart defects and to assess medical, behavioral, and individual factors that may be associated with the risk of autism spectrum disorders. Participants included 195 children with a history of congenital heart defects, who are followed in a large-scale longitudinal study. Measures included behavioral data from 4-year-old neurodevelopmental evaluations and parent-report data from a later annual follow-up. Using established cutoffs on an autism spectrum disorder screener, children with congenital heart defects showed higher rates of "possible" autism spectrum disorders than national rates, (Chi-square Test of Equal Proportions), all Ps < .05. A stepwise variable selection method was used to create a "best prediction model" and multivariable logistic regression was used to identify variables predicting diagnostic status. Factors associated with diagnostic risk included medical (delayed sternal closure, prematurity, positive genetic findings), behavioral (cognitive, language, attention issues), and individual (socioeconomic, cultural/racial) variables. ROC analyses identified a cutoff of 7 to maximize sensitivity/specificity based on parent-reported diagnosis. Risk of autism spectrum disorder screening status in children with congenital heart defects was higher than expected from population rates. Findings highlight the need for referral to a specialist to assess the presence and severity of social-communication issues and congenital heart defects population-specific screening thresholds for children with concern for autism spectrum disorders.


Feature Compression Applications of Genetic Algorithm.
With the rapid development of molecular breeding technology and many new varieties breeding, a method is urgently needed to identify different varieties accurately and quickly. Using this method can not only help farmers feel convenient and efficient in the normal cultivation and breeding process but also protect the interests of breeders, producers and users. In this study, single nucleotide polymorphism (SNP) data of 533 Oryza sativa, 284 Solanum tuberosum and 247 Sus scrofa and 544 Manihot esculenta Crantz were used. The original SNPs were filtered and screened to remove the SNPs with deletion number more than 1% or the homozygous genotype 0/0 and 1/1 number less than 2. The correlation between SNPs were calculated, and the two adjacent SNPs with correlation R2 > 0.95 were retained. The genetic algorithm program was developed to convert the genotype format and randomly combine SNPs to calculate a set of a small number of SNPs which could distinguish all varieties in different species as fingerprint data, using Matlab platform. The successful construction of three sets of fingerprints showed that the method developed in this study was effective in animals and plants. The population structure analysis showed that the genetic algorithm could effectively obtain the core SNPs for constructing fingerprints, and the fingerprint was practical and effective. At present, the two-dimensional code of Manihot esculenta Crantz fingerprint obtained by this method has been applied to field planting. This study provides a novel idea for the Oryza sativa, Solanum tuberosum, Sus scrofa and Manihot esculenta Crantz identification of various species, lays foundation for the cultivation and identification of new varieties, and provides theoretical significance for many other species fingerprints construction.


Customised assessment of fetal growth potential: implications for perinatal care.
Assessment of fetal growth is a central requirement for good perinatal care. The concept of the individually customised growth potential has enhanced our understanding of the importance of intrauterine growth restriction and its effects on pregnancy outcome. Prospectively, it provides a promising tool for improving antenatal detection, and highlights the need for appropriate protocols and pathways, training and resources to implement effective strategies for prevention.


Side chain variations on a series of dicyanovinyl-terthiophenes: a photoinduced absorption study.
We characterize a series of dicyanovinyl-terthiophenes with different alkyl side chains. Variations of side chain substitution patterns and length mainly affect the morphology of the evaporated thin films, which in turn sensitively influences properties like absorption, energy levels, and thin film roughness. To investigate changes in transfer processes between electron donor (D) and acceptor (A) molecules due to side chain variations, we use photoinduced absorption spectroscopy (PIA). PIA probes the long-living photoexcited species at the D-A interface: triplet excitons, cations, and anions. For a blend layer of dicyanovinyl-terthiophene and the electron acceptor fullerene C(60), an energy transfer via the singlet and triplet manifold of C(60) occurs. The recombination dynamics of the triplet excitons reveal two components that differ in their lifetime and generation rate by 1 order of magnitude. By comparing the dynamics of triplet excitons in neat and blend layers, we estimate the energy transfer efficiency in dependence of the type of side chain. The compound with methyl side chains shows remarkable properties regarding thin film absorption, surface roughness, and energy transfer efficiency, which we attribute to the specific nanomorphology of the thin film.


Carbon Inverse Opal Rods for Nonenzymatic Cholesterol Detection.
Carbon inverse opal rods made from silica photonic crystal rods are used for nonenzymatic cholesterol sensing. The characteristic reflection peak originating from the physical periodic structure works as sensing signals for quantitatively estimating cholesterol concentrations. Carbon inverse opal rods work both in cholesterol standard solutions and human serum. They are suitable for practical use in clinical diagnose.


Transcription factor nuclear factor erythroid-2 mediates expression of the cytokine interleukin 8, a known predictor of inferior outcome in patients with myeloproliferative neoplasms.
The transcription factor nuclear factor erythroid-2 is over-expressed in patients with myeloproliferative neoplasms irrespective of the presence of the JAK2(V617F) mutation. Our transgenic mouse model over-expressing nuclear factor erythroid-2, which recapitulates many features of myeloproliferative neoplasms including transformation to acute myeloid leukemia, clearly implicates this transcription factor in the pathophysiology of myeloproliferative neoplasms. Because the targets mediating nuclear factor erythroid-2 effects are not well characterized, we conducted microarray analysis of CD34(+) cells lentivirally transduced to over-express nuclear factor erythroid-2 or to silence this transcription factor via shRNA, in order to identify novel target genes. Here, we report that the cytokine interleukin 8 is a novel target gene. Nuclear factor erythroid-2 directly binds the interleukin 8 promoter in vivo, and these binding sites are required for promoter activity. Serum levels of interleukin 8 are known to be elevated in both polycythemia vera and primary myelofibrosis patients. Recently, increased interleukin 8 levels have been shown to be predictive of inferior survival in primary myelofibrosis patients in multivariate analysis. Therefore, one of the mechanisms by which nuclear factor erythroid-2 contributes to myeloproliferative neoplasm pathology may be increased interleukin 8 expression.


Correlation study of DNA methylation of WNT6 gene with osteosarcoma in children.
The aim of this study was to evaluate the status and explore the impact of DNA methylation of WNT6 gene with osteosarcoma in children. A total of 50 patients with primary osteosarcoma in children were enrolled. The expression of WNT6 protein was determined by immunohistochemical staining. The DNA methylation level of WNT6 gene was evaluated by methylation-specific PCR (MSP). Human MG63 osteosarcoma cells and human normal Hfob1.19 osteoblasts were selected and cultured. Western blot analysis was utilized to measure the expression of WNT6 in the two cell lines. MSP was used to assess the status of DNA methylation of WNT6 gene. The correlation between DNA methylation of WNT6 gene and prognosis of osteosarcoma in children was evaluated by statistical analysis of the clinical and prognostic data. The results of the immunohistochemical assay showed that 84% (42/50) of primary osteosarcoma was WNT6 positive. MSP indicated that DNA methylation of WNT6 gene was found in 9 cases (18%) of primary osteosarcoma. Western blot analysis showed that WNT6 protein expression in MG63 cells was significantly higher than that in normal human Hfob1.19 osteoblasts, whereas, the level of DNA methylation of WNT6 gene in MG63 cells was significantly lower than in Hfob1.19 cells. Analysis of survival, prognosis and their correlation found that the DNA methylation level of WNT6 gene was negatively correlated with the prognosis of children with osteosarcoma. In conclusion, there was a high level of WNT6 gene expression in primary osteosarcoma, which was mainly due to low DNA methylation level of WNT6 gene. The DNA methylation of WNT6 gene was negatively correlated with the prognosis of patients with osteosarcoma in children.


A close-coupling study of vibrational-rotational quenching of CO by collision with hydrogen atoms.
Quantum-mechanical scattering calculations were performed for the rovibrational relaxation of CO in collisions with H atoms using the close-coupling approach for collision energies between 10(-6) and 1500 cm(-1). We adopted the H-CO interaction potential of Werner, Keller, and Schinke and computed the state-to-state and total cross sections for the quenching of the upsilon=1, j=0-2 levels of CO. Numerous resonances, as a consequence of the van der Waals potential, are observed and the cross sections are found to approach the Wigner limit at low energies. Also, by averaging the cross sections over a Boltzmann distribution of velocities of the incoming atom, quenching rate coefficients are obtained and found to be consistent with previous infinite-order sudden approximation calculations for temperatures between 100 and 300 K.


Association with MDCK epithelial cells by Salmonella typhimurium is reduced during utilization of carbohydrates.
Association of Salmonella typhimurium with MDCK epithelial cells in monolayers, represented primarily by intracellular bacteria after 30 min of contact, with centrifugation followed by vigorous washing, was measured during aerobic and anaerobic growth of the bacteria in brain heart infusion broth. Cell association was greatest during a short period in the late log phase of growth under aerobic conditions. At this time, the pH of the growth medium was changing from acid to alkaline and glucose (0.2% initially) was exhausted. Addition of excess glucose (0.5%) to brain heart infusion broth, which was not exhausted before the bacteria entered the stationary phase of growth, in which cell association dropped sharply, resulted in repression of cell association by the bacteria. The repressive effect of glucose on cell association could not be reversed by exogenous cyclic AMP in the bacterial growth medium. Under anaerobic conditions, the effect of glucose on cell association by the bacteria was not as great and the glucose was not exhausted before the bacteria entered the stationary phase. When S. typhimurium was grown in a rich but carbohydrate-free medium, cell association by the bacteria increased earlier in the growth cycle under both aerobic and anaerobic conditions. The addition of glucose and certain other utilizable carbohydrates to this medium caused a repression of cell association by S. typhimurium that was greater under aerobic growth conditions. These results show that cell association by S. typhimurium, which is accompanied by rapid internalization (cell invasion), is the same under aerobic and anaerobic conditions if the bacteria are grown to the log phase in a carbohydrate-free medium. This suggests that prior reports of greater cell invasion by S. typhimurium during anaerobic growth may have arisen from the use of media containing carbohydrates which were found to be more repressive during aerobic growth of the bacteria.


Mycobacterium tuberculosis of the RDRio genotype is the predominant cause of tuberculosis and associated with multidrug resistance in Porto Alegre City, South Brazil.
Spoligotyping has shown Mycobacterium tuberculosis strains to be composed of different lineages, and some of them are not just geographically restricted but also affect specific ethnic populations and are associated with outbreaks and drug resistance. We recently described a particular subtype within the Latin American-Mediterranean (LAM) family, called RD(Rio), widespread in Brazil. Moreover, recent data also indicate that RD(Rio) is present in many countries on all continents and is associated with cavitary disease and multidrug resistance (MDR). To further explore the relationship between RD(Rio) and MDR, we conducted a study in a tuberculosis (TB) reference center responsible for the care of MDR patients in Rio Grande do Sul, the southernmost Brazilian state. From a collection of 237 clinical isolates, RD(Rio) alone was responsible for one-half of all MDR cases, including one large group composed of strains with identical IS6110-restriction fragment length polymorphism (RFLP) and having the LAM5 signature. We additionally had complete data records for 96 patients and could make comparisons between the presence and absence of RD(Rio). No difference in clinical, radiological or laboratory features was observed, but a significantly greater number of cases with MDR were described in patients infected with an RD(Rio) strain (P = 0.0015). Altogether, RD(Rio) was responsible for 38% of all TB cases. These data support and confirmed previous findings that RD(Rio) is the main agent responsible for TB in Brazil and is associated with drug resistance. Considering that RD(Rio) is a globally distributed genotype, such findings raise concern about the increase in MDR in certain human populations.


Facile Synthesis of F-TiO2/TiOF2 Mixture by High-Thermal Direct Fluorination and Its Photocatalytic Evaluation.
In this study, the mixture of F-TiO2/TiOF2 has been easily synthesized using titanium (IV) isopropoxide (TTIP) as titanium source by direct fluorination at high temperature according to different partial pressure of fluorine gas. The morphological properties and crystalline of thermally fluorinated photocatalysts were investigated using scanning electron microscope (SEM) and X-ray diffraction (XRD). Chemical composition and optical properties of thermally fluorinated photocatalysts were analyzed by X-ray Photoelectron Spectroscopy (XPS) and Photoluminescence (PL) spectrometer. The phase of F-TiO2/TiOF2 mixture was generated with different proportion by high-thermal direct fluorination. With the increase of the fluorine partial pressure, the proportion of cubic-shaped TiOF2 increased in comparison with globular-shaped TiO2. Also, the degradation rate constant of thermally fluorinated photocatalysts exhibited approximately 70 times more than that of TiO2, which were not treated fluorine gas. It is attributable to the increase of the surface hydroxyl group content and oxygen vacancies.


Early non-invasive diagnosis of cervical cancer: beyond Pap smears and human papilloma virus (HPV) testing.
Cervical cancer is a major gynecologic malignancy around the world. However, current diagnostic methods such as Pap smear and human papilloma virus (HPV) testing are insufficient for an early diagnosis of cervical cancer, follow-up on therapy efficacy or to identify the women who might progress to cervical cancer (only about 1-5% of the HPV-positive women will develop cervical cancer). Patients with atypical squamous cells of undetermined significance (ASC-US) clearly need a better screening test. Developing a non-invasive method for early diagnosis of cervical cancer is essential. Our in vitro and translational research data support the hypothesis that: 1. Squamous cell cervical cancer is related to specific upregulation of tissue and serum Insulin-like Growth Factor-II levels (IGF-II; 100% sensitivity and 100% specificity). Serum IGF-I, but not IGF-II levels are elevated in other gynecological, breast, lung and prostate cancers. Serum IGF-II test helps in diagnosing cervical cancer as early as ASC-US or cervical intraepithelial neoplasia (CIN)-I and in monitoring therapy efficacy (p < 0.001 by Student's 't' test and Chi-square analysis). 2. Concomittant to increased serum IGF-II levels, IGF-Binding Protein 3 (IGF-BP3) levels are significantly decreased in persistent CIN and cervical cancer (p < 0.0001). As IGF-BP3 modulates IGF-II biological activity, significantly decreased serum IGF-BP3 levels (levels normalize after therapy; p < 0.001) may indicate a poor prognosis. Similar to serum IGF-II, serum IGF-BP3 levels help monitoring therapy efficacy in cervical cancer and advanced CIN. Measurement of serum IGF-II levels will help in early diagnosis of cervical cancer and monitoring of therapy outcome. Serum IGF-BP3 in conjunction with IGF-II levels may help in predicting prognosis as well as monitoring therapy efficacy.


Acute toxicity of fluazinam to aquatic organisms and its bioaccumulation in Brachydanio rerio.
Fluazinam (FZN) is a dinitroaniline fungicide. To evaluate the environmental risk of FZN in aquatic environments and ascertain the potential danger to typical aquatic organisms in China, the acute toxicity of FZN to representative aquatic organisms, including Brachydanio rerio, Chlorella vulgaris Beij., Daphnia magna Straus, and Xenopus laevis, was measured, and its bioaccumulation properties in Brachydanio rerio were further investigated. The results showed that the acute toxicity of FZN to Brachydanio rerio and Xenopus laevis is extremely high, and the bioaccumulation factor BCF8d of FZN in Brachydanio rerio ranges between 2287 and 3570, implying that it has high bioaccumulation properties. FZN poses a strong environmental risk for aquatic organisms and possesses great bioaccumulation properties, which may cause pollution to aquatic environments.


Non-homologous end joining plays a key role in transgene concatemer formation in transgenic zebrafish embryos.
This study focused on concatemer formation and integration pattern of transgenes in zebrafish embryos. A reporter plasmid based on enhanced green fluorescent protein (eGFP) driven by Cytomegalovirus (CMV) promoter, pCMV-pax6in-eGFP, was constructed to reflect transgene behavior in the host environment. After removal of the insertion fragment by double digestion with various combinations of restriction enzymes, linearized pCMV-pax6in-eGFP vectors were generated with different combinations of 5'-protruding, 3'-protruding, and blunt ends that were microinjected into zebrafish embryos. Repair of double-strand breaks (DSBs) was monitored by GFP expression following religation of the reporter gene. One-hundred-and-ninety-seven DNA fragments were amplified from GFP-positive embryos and sequenced to analyze the repair characteristics of different DSB end combinations. DSBs involving blunt and asymmetric protruding ends were repaired efficiently by direct ligation of blunt ends, ligation after blunting and fill-in, or removed by cutting. Repair of DSBs with symmetric 3'-3' protrusions was less efficient and utilized template-directed repair. The results suggest that non-homologous end joining (NHEJ) was the principal mechanism of exogenous gene concatemer formation and integration of transgenes into the genome of transgenic zebrafish.


Epiregulin is a potent pan-ErbB ligand that preferentially activates heterodimeric receptor complexes.
The ErbB signaling network consists of four transmembrane receptor tyrosine kinases and more than a dozen ligands sharing an epidermal growth factor (EGF) motif. The multiplicity of ErbB-specific ligands is incompletely understood in terms of signal specificity because all ErbB molecules signal through partially overlapping pathways. Here we addressed the action of epiregulin, a recently isolated ligand of ErbB-1. By employing a set of factor-dependent cell lines engineered to express individual ErbBs or their combinations, we found that epiregulin is the broadest specificity EGF-like ligand so far characterized: not only does it stimulate homodimers of both ErbB-1 and ErbB-4, it also activates all possible heterodimeric ErbB complexes. Consistent with its relaxed selectivity, epiregulin binds the various receptor combinations with an affinity that is approximately 100-fold lower than the affinity of ligands with more stringent selectivity, including EGF. Nevertheless, epiregulin's action upon most receptor combinations transmits a more potent mitogenic signal than does EGF. This remarkable discrepancy between binding affinity and bioactivity is permitted by a mechanism that prevents receptor down-regulation, and results in a weak, but prolonged, state of receptor activation.


Histone modifications affect differential regulation of TGFβ- induced NADPH oxidase 4 (NOX4) by wild-type and mutant p53.
Previously, we showed wild-type (WT) and mutant (mut) p53 differentially regulate reactive oxygen species (ROS) generation by NADPH oxidase-4 (NOX4): p53-WT suppresses TGFβ-induced NOX4, ROS and cell migration, whereas tumor-associated mut-p53 proteins enhance NOX4 expression and cell migration. Here, we extended our findings on the effects of p53 on NOX4 in several tumors and examined the basis of NOX4 transcriptional regulation by p53 and SMAD3. Statistical analysis of expression data from primary tumors available from The Cancer Genome Atlas (TCGA) detected correlations between mut-p53 and increased NOX4 expression. Furthermore, by altering p53 levels in cell culture models we showed several common tumor-associated mutant forms support TGFβ/SMAD3-dependent NOX4 expression. Deletion analysis revealed two critical SMAD3 binding elements (SBE) required for mut-p53-dependent NOX4 induction, whereas p53-WT caused dose-dependent suppression of NOX4 transcription. ChIP analysis revealed SMAD3 and p53-WT or mut-p53 associate with SBEs and p53 response elements in a TGFβ-dependent manner. Interestingly, the repressive effects of p53-WT on NOX4 were relieved by mutation of its transactivation domain or histone deacetylase (HDAC) inhibitor treatment. Overexpression of p300, a transcriptional co-regulator and histone acetyltransferase (HAT), enhanced p53-mediated NOX4 induction, whereas HAT-inactive p300 reduced NOX4 expression. Mut-p53 augmented TGFβ-stimulated histone acetylation within the NOX4 promoter. Finally, wound assays demonstrated NOX4 and p300 promote TGFβ/mut-p53-mediated cell migration. Our studies provide new insight into TGFβ/SMAD3 and mut-p53-mediated NOX4 induction involving epigenetic control of NOX4 in tumor cell migration, suggesting NOX4 is a potential therapeutic target to combat tumor progression and metastasis.


Polyprenyl Immunostimulant Treatment of Cats with Presumptive Non-Effusive Feline Infectious Peritonitis In a Field Study.
Feline infectious peritonitis (FIP) is a fatal disease with no clinically effective treatment. This field study evaluated treatment with Polyprenyl Immunostimulant (PI) in cats with the non-effusive form of FIP. Because immune suppression is a major component in the pathology of FIP, we hypothesized that treatment with an immune system stimulant would increase survival times of cats with dry FIP. Sixty cats, diagnosed with dry FIP by primary care and specialist veterinarians and meeting the acceptance criteria, were treated with PI without intentional selection of less severe cases. The survival time from the start of PI treatment in cats diagnosed with dry FIP showed that of the 60 cats with dry FIP treated with PI, 8 survived over 200 days, and 4 of 60 survived over 300 days. A literature search identified 59 cats with non-effusive or dry FIP; no cat with only dry FIP lived longer than 200 days. Veterinarians of cats treated with PI that survived over 30 days reported improvements in clinical signs and behavior. The survival times in our study were significantly longer in cats who were not treated with corticosteroids concurrently with PI. While not a cure, PI shows promise in the treatment of dry form FIP, but a controlled study will be needed to verify the benefit.


Implementation of an Asthma Self-Management Education Guideline in the Emergency Department: A Feasibility Study.
Patients often present to emergency departments (EDs) for the management of chronic asthma. Because of the nature of ED care, national guideline recommendations for asthma education are generally not initiated in the ED. There is evidence that asthma education can have a positive effect on patient outcomes (; ). This study examines the feasibility of implementing an asthma self-management guideline in a tertiary care center ED. Despite protocol utilization by physicians (87%), nurse practitioners and physician assistants (66.7%), and nurses (41.7%), total compliance with national guideline was accomplished in only 25.93% of cases. Barriers to protocol implementation included staff education, high workload, rapid turnover, and competing initiatives within the department. Linear regression analysis identified high daily census as a predictor of protocol noncompliance (p = 0.033).


Mapping the Product Range of Interdental Brushes: Sizes, Shapes, and Forces.
Preventive dentistry aims to improve oral hygiene, including the use of interdental cleansing aids. Clear and simple classifications may positively impact patient communication and motivate oral health behaviour. To date, there is no comparative analysis of interdental brush classifications and sizes. A total of 2320 interdental brush samples by 24 manufacturers was examined regarding their passage hole diameter (PHD) according to the ISO standard for interdental brushes (ISO16409:2016), and their current classifications were evaluated. Inter- and intrarater reliability of the ISO size classification were determined based on 20 raters and 10 interdental brushes. The insertion force for these interdental brushes was analysed in vitro. Excellent intra- and interrater reliability was achieved (intraclass correlation coefficient (ICC) ≥ 0.973) overall, although greater variance was observed for bigger brush sizes. Insertion forces varied depending on size and form of the brushes, amounting to 1.58 N (SD = 1.27 N) for cylindric and tapered brushes, and to 2.31 N (SD = 0.81 N) for waist-shaped brushes. The size range of commercially available products was 0.6-5.2 mm PHD, 90% presenting with a PHD ≤ 2.0 mm. Size intervals were unsystematic. The ISO size was indicated by 33% of all manufacturers, the exact PHD by 25%. The determination of the PHD is a reproducible instrument for most brushes currently on the market. In vitro, forces developed based on this classification are mostly moderate, thus unlikely to cause periodontal trauma. Given the discontinuous range and unclear labelling of available products, the development of a simplified classification system by usage of the PHD may benefit the practitioner and patient alike by contributing to improve oral hygiene behaviours.