Parental Leave Use among Disadvantaged Fathers.
The United States lags behind other industrialized countries in its lack of inclusive and standardized parental leave policy after the birth or adoption of a child. Using data from the Fragile Families and Child Wellbeing Study (N=2,233), this study examines the patterns and predictors of fathers' parental leave use, as well as its association with father-child engagement. Our findings indicate that the vast majority of employed fathers take parental leave, but they rarely take more than one week of leave. Fathers who have more positive attitudes about fatherhood and who live with the birth mother are especially likely to take leave, and to take more weeks of leave, than other fathers. Finally, we find that taking parental leave, and taking more weeks of parental leave, is positively associated with father engagement levels at one year and five years after the birth of his child.


Monochromatic x-ray sampling streak imager for fast-ignitor plasma observation.
Ultrafast two-dimensional (2D) x-ray imaging is required to investigate the dynamics of fast-heated core plasma in inertial confinement fusion research. A novel x-ray imager, consisting of two toroidally bent Bragg crystals and an ultrafast 2D x-ray imaging camera, has been demonstrated. Sequential and 2D monochromatic x-ray images of laser-imploded core plasma were obtained with a temporal resolution of 20 ps, a spatial resolution of 31 mum, and a spectral resolution of over 200, simultaneously.


Gating of hole transfer from photoexcited PbS quantum dots to aminoferrocene by the ligand shell of the dots.
Photoinduced hole transfer from PbS quantum dots (QDs) to aminoferrocene only occurs if the ligand shell of the QD allows aminoferrocene to gain direct access to the inorganic core of the QD; the permeability of the ligand shell is therefore more important than its conductivity in determining the probability of interfacial charge transfer.


Arcuate foramen of atlas: incidence, phylogenetic and clinical significance.
Arcuate foramen is less known trait of the human atlas vertebra formed by a delicate bony spiculum, which arches backward from the posterior end of the superior articular process. Examination of 1044 human atlas vertebra revealed that the trait was present in 13.8% of the samples. The mean length of the arcuate foramen form was 7.16 mm on the left side and 9.99 mm on the right side in bilateral positive samples while it was 8.14 mm and 9.26 mm respectively in unilateral positive samples. The mean vertical height of this foramen was 6.57 mm on the left side and 6.52 mm on the right side in bilateral positive samples while it was 4.91 mm and 5.38 mm respectively in unilateral positive samples. The sides did not show any statistical significant differences. The importance of the arcuate foramen lies in the external pressure it may cause on the vertebral artery as it passes from the foramen transversarium of the first cervical vertebra to the foramen magnum of the skull.


Beef herd poisoning due to ingestion of tansy ragwort in southwestern Ontario.
Deaths attributed to Senecio jacobaea were investigated. The animal presented was a mature bull that was lethargic and dragging its feet. The bull was euthanized and 3 other cows died. Significantly, this disease has not been documented in Ontario before, and clinical signs of icterus or hepatoencephalopathy were not observed.


Circ_0001982 aggravates breast cancer development through the circ_0001982-miR-144-3p-GSE1 axis.
This study was designed to explore the role of circ_0001982 in breast cancer (BC) development. Quantitative real-time polymerase chain reaction and western blot analysis assays were used to determine circ_0001982, miR-144-3p, and gse1 coiled-coil protein (GSE1) expression. Functional assays were performed to evaluate cell proliferation, apoptosis, migration, and invasion. The glycolysis was analyzed with commercial kits. Dual-luciferase reporter assay and RNA immunoprecipitation assays were conducted to analyze the relationships among circ_0001982, miR-144-3p, and GSE1. A murine xenograft model assay was performed to determine circ_0001982-induced effects on BC cell tumor properties in vivo. Circ_0001982 expression was upregulated, but miR-144-3p was reduced in BC tissues and cells in comparison with normal breast tissues and normal human mammary epithelial cells. Circ_0001982 knockdown or miR-144-3p overexpression inhibited BC cell proliferation, glycolysis, migration and invasion, and promoted apoptosis. Circ_0001982 sponged miR-144-3p and negatively regulated miR-144-3p expression in BC cells. In addition, GSE1 was identified as a target mRNA of miR-144-3p. Ectopic GSE1 expression relieved circ_0001982 depletion-induced effects on BC cell tumor properties. Furthermore, circ_0001982 absence suppressed BC cell tumor properties in vivo. Circ_0001982 contributed to the BC cell tumor properties by regulating the miR-144-3p-GSE1 axis.


Effect of observation on lower limb prosthesis gait biomechanics: Preliminary results.
The Hawthorne effect, a subcategory of reactivity, causes human behavior to change when under observation. Such an effect may apply to gait variation of persons with prosthetics or orthotics devices. This study investigated whether the presence of observers directly affects the gait pattern of users of lower limb prostheses. Within-subject intervention study. Primary outcome measures were gait parameters of initial double support time and upper body lateral tilt angle, which were collected with a mobile sensor attached to the subjects' back. To make subjects feel unwatched, a certain amount of deception was necessary, and two different conditions were created and statistically compared against each other: one in which the subjects were initially unaware of the attention of observers and another one in which the same subjects were aware of a group of observers. Data from two subjects using trans-femoral prosthesis are reported. Findings included a change in step initial double support percentage by up to 14.2% (p = 0.019). Considerable changes were also noted in secondary outcome measures including speed, stride length, and stride symmetry. A reactivity effect of observation exists in prosthetics gait analysis. More comprehensive studies may be motivated by these preliminary findings. Results of this study suggest that users of lower limb prostheses walk differently when their gait is being assessed (e.g. in the prosthetist's office) than in situations without observers. This may in part explain the clinical experience that modifications of prosthetic fit or alignment provide only short-term betterment.


Automatic segmentation of liver tumors from multiphase contrast-enhanced CT images based on FCNs.
This paper presents a novel, fully automatic approach based on a fully convolutional network (FCN) for segmenting liver tumors from CT images. Specifically, we designed a multi-channel fully convolutional network (MC-FCN) to segment liver tumors from multiphase contrast-enhanced CT images. Because each phase of contrast-enhanced data provides distinct information on pathological features, we trained one network for each phase of the CT images and fused their high-layer features together. The proposed approach was validated on CT images taken from two databases: 3Dircadb and JDRD. In the case of 3Dircadb, using the FCN, the mean ratios of the volumetric overlap error (VOE), relative volume difference (RVD), average symmetric surface distance (ASD), root mean square symmetric surface distance (RMSD) and maximum symmetric surface distance (MSSD) were 15.6±4.3%, 5.8±3.5%, 2.0±0.9%, 2.9±1.5mm, 7.1±6.2mm, respectively. For JDRD, using the MC-FCN, the mean ratios of VOE, RVD, ASD, RMSD, and MSSD were 8.1±4.5%, 1.7±1.0%, 1.5±0.7%, 2.0±1.2mm, 5.2±6.4mm, respectively. The test results demonstrate that the MC-FCN model provides greater accuracy and robustness than previous methods.


Mitogen-Activated Protein Kinase OsMEK2 and OsMPK1 Signaling Is Required for Ferroptotic Cell Death in Rice-Magnaporthe oryzae Interactions.
Mitogen-activated protein kinase (MAPK) signaling is required for plant cell death responses to invading microbial pathogens. Iron- and reactive oxygen species (ROS)-dependent ferroptotic cell death occurs in rice (Oryza sativa) during an incompatible rice-Magnaporthe oryzae interaction. Here, we show that rice MAP kinase (OsMEK2 and OsMPK1) signaling cascades are involved in iron- and ROS-dependent ferroptotic cell death responses of rice to M. oryzae infection using OsMEK2 knock-out mutant and OsMEK2 and OsMPK1 overexpression rice plants. The OsMPK1:GFP and OsWRKY90:GFP transcription factor were localized to the nuclei, suggesting that OsMPK1 in the cytoplasm moves into the nuclei to interact with the WRKY90. M. oryzae infection in ΔOsmek2 knock-out plants did not trigger iron and ROS accumulation and lipid peroxidation, and also downregulated OsMPK1, OsWRKY90, OsRbohB, and OsPR-1b expression. However, 35S:OsMEK2 overexpression induced ROS- and iron-dependent cell death in rice. The downstream MAP kinase (OsMPK1) overexpression induced ROS- and iron-dependent ferroptotic cell death response to virulent M. oryzae infection. The small-molecule ferroptosis inhibitor ferrostatin-1 suppressed iron- and ROS-dependent ferroptotic cell death in 35S:OsMPK1 overexpression plants. However, the small-molecule inducer erastin triggered iron- and lipid ROS-dependent, but OsMEK2-independent, ferroptotic cell death during M. oryzae infection. Disease (susceptibility)-related cell death was lipid ROS-dependent, but iron-independent in the ΔOsmek2 knock-out mutant during the late M. oryzae infection stage. These combined results suggest that OsMEK2 and OsMPK1 expression positively regulates iron- and ROS-dependent ferroptotic cell death, and blast disease (susceptibility)-related cell death was ROS-dependent but iron-independent in rice-M. oryzae interactions.


Neutrophil priming occurs in a sequential manner and can be visualized in living animals by monitoring IL-1β promoter activation.
Rapid enhancement of phagocyte functionality is a hallmark of neutrophil priming. GeneChip analyses unveiled elevated CD54, dectin-2, and IL-1β mRNA expression by neutrophils isolated from inflammatory sites. In fact, CD54 and dectin-2 protein expression was detected on neutrophils recovered from skin, peritoneal, and lung inflammation lesions but not on those in bone marrow or peripheral blood. Neutrophils increased CD54 and dectin-2 mRNA during migration in Boyden chambers and acquired CD54 and dectin-2 surface expression after subsequent exposure to GM-CSF. Neutrophils purified from IL-1β promoter-driven DsRed-transgenic mice acquired DsRed signals during cell migration or exposure to GM-CSF. CD54 and dectin-2 were expressed by DsRed(+) (but not DsRed(-)) neutrophils in GM-CSF-supplemented cultures, and neutrophils recovered from inflammatory sites exhibited strong DsRed signals. The dynamic process of neutrophil priming was studied in chemically induced inflammatory skin lesions by monitoring DsRed expression using confocal microscopy. A majority (>80%) of Ly6G(+) neutrophils expressed DsRed, and those DsRed(+)/Ly6G(+) cells exhibited crawling motion with a higher velocity compared with their DsRed(-)/Ly6G(+) counterparts. This report unveils motile behaviors of primed neutrophils in living animals. We propose that neutrophil priming occurs in a sequential manner with rapid enhancement of phagocyte functionality, followed by CD54 and dectin-2 mRNA and protein expression, IL-1β promoter activation, and accelerated motility. Not only do these findings provide a new conceptual framework for our understanding of the process of neutrophil priming, they also unveil new insights into the pathophysiology of many inflammatory disorders that are characterized by neutrophil infiltration.


Experimental and Computer Simulation Studies on Badminton Racquet Strings.
This study investigates experimentally, numerically, and analytically the performance of different string materials (Kevlar, synthetic gut, natural gut, and polyester) on badminton racquets. Vibration and impact tests with a shuttlecock were performed using a racquet frame made of carbon graphite mixed with epoxy resin. Different string tensions were considered in the tests (20, 22, 24, 28, 30, and 34 lb), as well as different hitting locations on the racquet frame. The results show that, as the diameter of the strings increased, the elasticity of the string decreased from 0.529 to 0.447 for diameters ranging from 0.62 to 0.70 mm. Subsequently, a badminton racquet and shuttlecock were modeled using SolidWorks2018® software (version 26), and a maximum displacement was applied to the ball to simulate an impact on the string bed. The natural frequency, maximum deformation and maximum stress were calculated analytically, and a finite element analysis was also performed using ANSYS2022 R2® software (version 22.2). The analytical and numerical results from ANSYS® showed good agreement (within 5% accuracy). The results of the study show that the natural frequency of a racquet with Kevlar strings was significantly higher than that of racquets with synthetic gut, natural gut, or polyester string materials. Specifically, the natural frequency of a racquet made of carbon graphite and epoxy resin was 23.0%, 30.7%, and 36.2% higher than that of racquets with synthetic gut, natural gut, and polyester string material, respectively. On the basis of this finding, Kevlar was chosen as the preferred material for badminton racquets strings, and a parametric analysis was then conducted. The study showed that slightly lowering the tension of the off-centered strings had a minimal effect on the von Mises stress distribution of the ball and string bed. In addition to investigating string materials, this study also examined the effects of pull and diameter variations of racquet strings on vibrations during impact. This study contributes to the understanding of the role of racquet and strings in badminton, and it also provides new insights into the factors that can affect performance in the sport. By analyzing the performance of different string materials and examining the effects of pull and diameter variations of racquet strings, this study provides valuable information for players and manufacturers looking to optimize their equipment for maximum performance.


AHNAK, a novel component of the dysferlin protein complex, redistributes to the cytoplasm with dysferlin during skeletal muscle regeneration.
Mutations in dysferlin cause limb girdle muscular dystrophy 2B, Miyoshi myopathy and distal anterior compartment myopathy. Dysferlin is proposed to play a role in muscle membrane repair. To gain functional insight into the molecular mechanisms of dysferlin, we have searched for dysferlin-interacting proteins in skeletal muscle. By coimmunoprecipitation coupled with mass spectrometry, we demonstrate that AHNAK interacts with dysferlin. We defined the binding sites in dysferlin and AHNAK as the C2A domain in dysferlin and the carboxyterminal domain of AHNAK by glutathione S-transferase (GST)-pull down assays. As expected, the N-terminal domain of myoferlin also interacts with the carboxyterminal domain of AHNAK. In normal skeletal muscle, dysferlin and AHNAK colocalize at the sarcolemmal membrane and T-tubules. In dysferlinopathies, reduction or absence of dysferlin correlates with a secondary muscle-specific loss of AHNAK. Moreover, in regenerating rat muscle, dysferlin and AHNAK showed a marked increase and cytoplasmic localization, consistent with the direct interaction between them. Our data suggest that dysferlin participates in the recruitment and stabilization of AHNAK to the sarcolemma and that AHNAK plays a role in dysferlin membrane repair process. It may also have significant implications for understanding the biology of AHNAK-containing exocytotic vesicles, "enlargosomes," in plasma membrane remodeling and repair.


A heat-stable blocking factor in the plasma of patients with subacute sclerosing panencephalitis.
The possible role of a defective cell-mediated immune response in the pathogenesis of subacute sclerosing panencephalitis remains unclear. Cell-mediated immunity has been investigated in nine patients with this disorder. In eight patients, a heat-stable blocking factor in the plasma inhibited normal lymphocyte transformation to phytohemagglutinin and mixed lymphocyte cultures. The degree of blocking increased as the disease progressed. The nature of the blocking factor is unknown and is currently under investigation. A heat-stable blocking factor has not been described previously in subacute sclerosing panencephalitis, althouth a heat-labile blocking factor has been reported in a total of five patients.


Impact of the maze procedure and postoperative atrial fibrillation on progression of functional tricuspid regurgitation in patients undergoing degenerative mitral repair.
The aim of this study is to investigate the factors contributing to the progression of functional tricuspid regurgitation (TR) after mitral repair for degenerative mitral regurgitation (MR) in relation to pre and postoperative atrial fibrillation (AF) and performance of the maze procedure. We assessed 398 patients with less than moderate TR who did not undergo tricuspid valve repair at the time of isolated mitral valve repair for degenerative MR between January 1999 and January 2010. Clinical follow-up was complete in 385 patients (96.7%) with a median follow-up of 48.3 months (range 0.13-148.5). During this time, there were 21 late deaths (5.5%) and 17 major complications (4.4%), including 11 reoperations for MR recurrence (2.9%). On late follow-up echocardiography performed on 395 patients (median 44.6 months, range 6.0-147.3), 34 (9.6%) experienced moderate or greater MR and 16 (4.5%) experienced moderate or greater TR. The 5-year freedom from moderate or greater MR and moderate or greater TR rates were 88.3 ± 2.1 and 95.3 ± 1.5%, respectively. Time-updated Cox regression analysis showed that male gender [hazard ratio (HR) 3.83, 95% confidence interval (CI) 1.28-11.40, P = 0.016], New York Heart Association functional class III or IV (HR 2.64, 95% CI 0.88-8.00, P = 0.085), preoperative AF without maze (HR 10.48, 95% CI 2.49-44.21, P = 0.001), and postoperative AF (HR 14.56, 95% CI 4.46-47.58, P < 0.001) were significant risk factors for postoperative moderate or greater TR. Of the 79 patients with preoperative AF, 68 (86.1%) underwent concomitant maze procedures. Of them, eight (11.8%) experienced late AF (>3 months) recurrence. Freedom from AF at 5 years after the concomitant maze procedure was 87.8 ± 4.6%. Preoperative AF without the maze procedure and postoperative AF can contribute to the development of moderate or greater functional TR after mitral repair for degenerative MR.


Cytoplasmic sequestration of the tumor suppressor p53 by a heat shock protein 70 family member, mortalin, in human colorectal adenocarcinoma cell lines.
While it is known that cytoplasmic retention of p53 occurs in many solid tumors, the mechanisms responsible for this retention have not been positively identified. Since heatshock proteins like mortalin have been associated with p53 inactivation in other tumors, the current study sought to characterize this potential interaction in never before examined colorectal adenocarcinoma cell lines. Six cell lines, one with 3 different fractions, were examined to determine expression of p53 and mortalin and characterize their cellular localization. Most of these cell lines displayed punctate p53 and mortalin localization in the cell cytoplasm with the exception of HCT-8 and HCT116 379.2 cells, where p53 was not detected. Nuclear p53 was only observed in HCT-116 40-16, LS123, and HT-29 cell lines. Mortalin was only localized in the cytoplasm in all cell lines. Co-immunoprecipitation and immunohistochemistry revealed that p53 and mortalin were bound and co-localized in the cytoplasmic fraction of four cell lines, HCT-116 (40-16 and 386; parental and heterozygous fractions respectively of the same cell line), HT-29, LS123 and LoVo, implying that p53 nuclear function is limited in those cell lines by being restricted to the cytoplasm. Mortalin gene expression levels were higher than gene expression levels of p53 in all cell lines. Cell lines with cytoplasmic sequestration of p53, however, also displayed elevated p53 gene expression levels compared to cell lines without p53 sequestration. Our data reveal the characteristic cytoplasmic sequestration of p53 by the heat shock protein mortalin in human colorectal adenocarcinoma cell lines, as is the case for other cancers, such as glioblastomas and hepatocellular carcinomas.


Customizable, wireless and implantable neural probe design and fabrication via 3D printing.
This Protocol Extension describes the low-cost production of rapidly customizable optical neural probes for in vivo optogenetics. We detail the use of a 3D printer to fabricate minimally invasive microscale inorganic light-emitting-diode-based neural probes that can control neural circuit activity in freely behaving animals, thus extending the scope of two previously published protocols describing the fabrication and implementation of optoelectronic devices for studying intact neural systems. The 3D-printing fabrication process does not require extensive training and eliminates the need for expensive materials, specialized cleanroom facilities and time-consuming microfabrication techniques typical of conventional manufacturing processes. As a result, the design of the probes can be quickly optimized, on the basis of experimental need, reducing the cost and turnaround for customization. For example, 3D-printed probes can be customized to target multiple brain regions or scaled up for use in large animal models. This protocol comprises three procedures: (1) probe fabrication, (2) wireless module preparation and (3) implantation for in vivo assays. For experienced researchers, neural probe and wireless module fabrication requires ~2 d, while implantation should take 30-60 min per animal. Time required for behavioral assays will vary depending on the experimental design and should include at least 5 d of animal handling before implantation of the probe, to familiarize each animal to their handler, thus reducing handling stress that may influence the result of the behavioral assays. The implementation of customized probes improves the flexibility in optogenetic experimental design and increases access to wireless probes for in vivo optogenetic research.


Association of hypoadiponectemia with smokeless/dipping tobacco use in young men.
Low levels of adiponectin, an adipocytokine with anti-diabetic, antiatherogenic and cardioprotective properties, is associated with increased risk of coronary disease in young men. Previous studies have demonstrated that smokeless tobacco is linked with a reduction of plasma adiponectin levels. However, the influence of smokeless tobacco (dipping tobacco) on plasma adiponectin levels still remains unknown. This study was conducted to assess the plasma adiponectin levels in young men who were using dipping tobacco. This was a community based study, which consisted of 186 young lean healthy males aged 20 to 35 years. Among these, 96 men were dipping tobacco users (BMI = 23.07 ± 2.68) and 90 were non-dipping tobacco users (BMI = 23.67 ± 1.46). Serum adiponectin levels were assessed by Enzyme Linked ImmunoSorbent Assay (ELISA). A statistically significant difference in the mean adiponectin level between tobacco dipper and non-dipper groups was observed (p = 0.0001). A significant difference between the two groups was also observed in baseline parameters including triglyceride and random blood sugar levels (p < 0.05). However, no significant difference was observed between the two groups in other clinical parameters. Findings of this study suggest that dipping tobacco use was significantly associated with low level of adiponetin in community dwelling young males. This emphasizes the importance of developing community intervention to reduce the use of dipping tobacco, which will reduce the tobacco associated disease burden in the community and will improve public health.


Genetics of hantaviruses: implications to taxonomy.
Hantaviruses (genus Hantavirus, family Bunyaviridae) represent a prime example of emerging viruses. Since isolation of the prototype Hantaan virus in the late 70s more than 20 new species have been described and the number is increasing fast thus demanding for a more refined classification. Taking into account that hantaviruses are difficult to isolate in cell culture, one should not be surprised that most of the "newcomers" were first described as distinct hantavirus genotypes. Moreover, the only "solid" characteristics of many hantavirus species still exist in the form of nucleotide sequences of their genome. The relatively short history of hantavirology can thus be taken to illustrate how genetics can contribute to (and even, perhaps, dominate) discovery, characterization and classification of viruses. In this review the following aspects of hantavirus genetics are discussed: (i) genome structure; (ii) genetic diversity and evolution; and (iii) use of genetic criteria in current taxonomy of hantaviruses. In addition, several examples of classification of hantavirus species (New York virus, Saaremaa virus and Hokkaido virus) are given, and future prospects are analyzed.


Characterization of metaproteomics in crop rhizospheric soil.
Soil rhizospheric metaproteomics is a powerful scientific tool to uncover the interactions between plants and microorganisms in the soil ecosystem. The present study established an extraction method suitable for different soils that could increase the extracted protein content. Close to 1000 separate spots with high reproducibility could be identified in the stained 2-DE gels. Among the spots, 189 spots representing 122 proteins on a 2-DE gel of rice soil samples were successfully identified by MALDI-TOF/TOF-MS. These proteins mainly originated from rice and microorganisms. They were involved in protein, energy, nucleotide, and secondary metabolisms, as well as signal transduction and resistance. Three characteristics of the crop rhizospheric metaproteomics seemed apparent: (1) approximately one-third of the protein spots could not be identified by MALDI-TOF/TOF/MS, (2) the conservative proteins from plants formed a feature distribution of crop rhizospheric metaproteome, and (3) there were very complex interactions between plants and microorganisms existing in a crop rhizospheric soil. Further functional analysis on the identified proteins unveiled various metabolic pathways and signal transductions involved in the soil biotic community. This study provides a paradigm for metaproteomic research on soil biology.


Neutralization of the edema-forming, defibrinating and coagulant effects of Bothrops asper venom by extracts of plants used by healers in Colombia.
We determined the neutralizing activity of 12 ethanolic extracts of plants against the edema-forming, defibrinating and coagulant effects of Bothrops asper venom in Swiss Webster mice. The material used consisted of the leaves and branches of Bixa orellana (Bixaceae), Ficus nymphaeifolia (Moraceae), Struthanthus orbicularis (Loranthaceae) and Gonzalagunia panamensis (Rubiaceae); the stem barks of Brownea rosademonte (Caesalpiniaceae) and Tabebuia rosea (Bignoniaceae); the whole plant of Pleopeltis percussa (Polypodiaceae) and Trichomanes elegans (Hymenophyllaceae); rhizomes of Renealmia alpinia (Zingiberaceae), Heliconia curtispatha (Heliconiaceae) and Dracontium croatii (Araceae), and the ripe fruit of Citrus limon (Rutaceae). After preincubation of varying amounts of each extract with either 1.0 microg venom for the edema-forming effect or 2.0 microg venom for the defibrinating effect, the mixture was injected subcutaneously (sc) into the right foot pad or intravenously into the tail, respectively, to groups of four mice (18-20 g). All extracts (6.2-200 microg/mouse) partially neutralized the edema-forming activity of venom in a dose-dependent manner (58-76% inhibition), with B. orellana, S. orbicularis, G. panamensis, B. rosademonte, and D. croatii showing the highest effect. Ten extracts (3.9-2000 microg/mouse) also showed 100% neutralizing ability against the defibrinating effect of venom, and nine prolonged the coagulation time induced by the venom. When the extracts were administered either before or after venom injection, the neutralization of the edema-forming effect was lower than 40% for all extracts, and none of them neutralized the defibrinating effect of venom. When they were administered in situ (sc at the same site 5 min after venom injection), the neutralization of edema increased for six extracts, reaching levels up to 64% for C. limon.


DNA methylation: hemodialysis versus hemodiafiltration.
Aberrant DNA methylation is an emerging characteristic of chronic kidney disease including dialysis patients. It appears to be associated to inflammation. We compared the global DNA methylation status in 10 control subjects compared to 80 dialysis patients (N = 40 on-line hemodiafiltration, N = 40 high-flux hemodialysis) in relation to the dialysis technique and inflammation. Whole blood DNA methylation was assessed with a 5-mc DNA enzyme linked immunosorbent assay Kit. Global DNA methylation was higher in hemodialysis (HD) compared to on-line hemodiafiltration (HDF) patients (0.045 vs. 0.039; P < 0.0001) and controls (0.045 vs. 0.0284; P = 0.0002 for HD; 0.039 vs. 0.0284; P = 0.0254 for on-line HDF). To study the influence of the dialysis technique on DNA methylation we divided dialysis patients according to the median value of 5-mC. DNA methylation was highest in inflamed patients on hemodialysis. The dialysis technique was the only independent predictor of global DNA methylation in dialysis patients. On-line HDF could be associated with a favorable DNA methylation profile.


Modelling population growth with delayed nonlocal reaction in 2-dimensions.
In this paper, we consider the population growth of a single species living in a two-dimensional spatial domain. New reaction-difusion equation models with delayed nonlocal reaction are developed in two-dimensional bounded domains combining diferent boundary conditions. The important feature of the models is the reflection of the joint efect of the difusion dynamics and the nonlocal maturation delayed efect. We consider and ana- lyze numerical solutions of the mature population dynamics with some wellknown birth functions. In particular, we observe and study the occurrences of asymptotically stable steady state solutions and periodic waves for the two-dimensional problems with nonlocal delayed reaction. We also investigate numerically the efects of various parameters on the period, the peak and the shape of the periodic wave as well as the shape of the asymptotically stable steady state solution.


[COVID-19 and features of cardiovascular involvement].
The article provides an overview of current information on the pathogenesis of COVID-19 and organ-specific lesions developing in this disease. The data on inflammation and its biochemical markers, on the features of coagulopathy, endothelial damage and microthrombosis are presented in detail. Particular attention is paid to the role of receptors for angiotensin converting enzyme type 2 and transmembrane serine protease type 2 in the development of organ-specific lesions in COVID-19. The pathogenesis of damage to the cardiovascular system is considered in detail with the presentation of data from foreign literature on changes in the myocardium and the author's results of transthoracic echocardiographic examination in patients who have undergone COVID-19.


Expression of claudin-1 and its relationship with lymphatic microvessel generation in hypopharyngeal squamous cell carcinoma.
We investigated the relationship between claudin-1 and micro-lymphatic vessel density (MLVD) by detecting claudin-1 and protein D2-40 expression in cancer tissue specimens obtained from 97 patients with hypopharyngeal squamous cell carcinoma (HSCC). We also explored the correlation between the expression of these proteins and clinical tumor stage, pathological grading, and clinical prognosis in the patients. Moreover, we studied the mechanism of lymph node metastasis in HSCC, thereby providing information for treating HSCC and inhibiting lymph node metastasis. We detected levels of claudin-1 and protein D2-40 expression in cancer tissue from 97 patients with HSCC and para-tumor tissue from 90 patients by immunohistochemistry; we analyzed the correlation between markers and clinicopathological features by using the Pearson chi-square test and conducted survival analysis by the log-rank test. Claudin-1 expression was high in HSCC and was related to tumor differentiation and lymph node metastasis; Kaplan-Meier analysis showed that claudin-1 expression was related to patient survival rate (P = 0.012). There was a significant relationship between MLVD in the tissues adjacent to the carcinoma and the indices of histopathological grade, clinical stage, and lymph node metastasis. There was also a positive correlation between claudin-1 expression and MLVD. High expression of claudin-1 might induce the generation of tumor lymphatic vessels, which increases metastasis in the lymph node. Because claudin-1 is related to patient survival rate, it may be useful as a monitoring index for postoperative HSCC and might be a new target for treating the disease.


A cost-effectiveness analysis of endoscopic third ventriculostomy.
Endoscopic third ventriculostomy (ETV) is currently the principal alternative to cerebrospinal fluid shunt placement in the management of pediatric hydrocephalus. Cost-effectiveness analysis can help determine the optimal strategy for integrating these different approaches. All patients (n = 28) who underwent ETV at British Columbia's Children's Hospital between 1989 and 1998 were matched for age, pathogenesis, and number of previous shunt procedures, with patients treated with cerebrospinal fluid shunts. To perform a cost-effectiveness analysis, hydrocephalus-related resource consumption and outcome (determined as the number of hydrocephalus treatment-free days during follow-up) were then retrospectively identified. Cost data were linked to resource use to provide a total cost for all resources used. Costs and outcomes were discounted annually at 5% by standard economic analysis methods. Twenty-four of 28 ETV patients had obstructive hydrocephalus. Over equivalent follow-up periods (median, 35 mo), the ETV success rate (defined by need for reoperation) was 54%. One hydrocephalus-related death and one hemiparesis occurred in the ETV group. No permanent procedure-related morbidity or mortality was seen in the shunt group. The cost/effect ratios for the two groups were similar. The additional incremental resource use by the shunt group included six readmissions and eight reoperations. ETV mean costs per patient were $10,570 +/- $7628, versus $10,922 +/- $8722 for the shunt group (Canadian dollars for the year 2000). Costs accrued more quickly for the shunt group as time passed. The additional incremental outcome benefit to the endoscopy group was 86 treatment-free days (3.07 d per patient [95% confidence interval, -7.56 to 13.70 d]). Neither of these differences was statistically significant. In this matched cohort, ETV was not significantly less costly or more effective over a median 35 months of follow-up, with a 54% initial ETV success rate, even before the additional morbidity and mortality encountered were taken into account. The time course for the accrued costs suggests that a larger cohort, longer follow-up, or higher success rates are needed to demonstrate the cost-effectiveness of this therapy.


Motivation to control one's environment in individuals with obsessive-compulsive, depressive, and normal personality traits.
This study investigated whether people are motivated for control and considered both the dispositional and situational factors that affect this motivation. Thirty male and 30 female undergraduates, divided equally among individuals with obsessive-compulsive, depressive, and normal personality styles, were given different levels of information about how to exercise control in an effective manner. Motivation for control was assessed by performance on a task in which the level of performance determined whether a subject obtained control over an outcome. In addition, feelings of self-efficacy were measured. The hypothesis that people are motivated to have personal control was confirmed. Furthermore, this motivation for control could not be accounted for by the variance attributable to feelings of self-efficacy, that is, the expectancy of gaining a good outcome by having personal control. Although feelings of self-efficacy were influenced by the level of information provided to subjects, for most subjects, the motivation for control, per se, was not affected. In contrast, obsessive-compulsive males seemed to respond differently to the information manipulation from other subjects, being motivated for control only when a higher level of information was provided. The effects of depressive and obsessive-compulsive personality styles on the motivation for control were reconsidered.


The effect of varying diagnostic thresholds upon clinical caries data for a low prevalence group.
This study investigated the impact of employing differing diagnostic thresholds on clinical caries data in studies of groups with low caries prevalence. Data from clinical examinations of 287 Hong Kong dental students were analyzed by means of the CARIES microcomputer software package. This software allows for re-calculation of raw data according to three different diagnostic thresholds (D3, D2, and D1). When "enamel" and "initial" lesions (as defined by WHO criteria) were included in the calculation of DMFT, its value increased from 3.0 (D3) to 5.9 (D1), while the percentage of individuals considered "caries-free" decreased from 28.2% to 7.0%. Little change was found in the magnitude of the intra-examiner reproducibility, when calculated at each threshold, for a random 10% of the subjects. It was unfortunately not possible to calculate inter-examiner reproducibility in this study. The use of criteria which might be misinterpreted as being similar, but which use differing effective diagnostic thresholds, can dramatically influence the reported level of dental caries. In view of these findings, it may be necessary for the question of diagnostic thresholds to be re-examined and to receive greater emphasis in future studies.


[A simple bite protector for the laryngeal mask].
A new simple gag is presented securing the width of the tube of the laryngeal mask. The device is a 45 degrees-angled, u-shaped, synthetic-coated aluminium rod. This gag, while being additionally an aid to ensure the proper position of the laryngeal mask, is easy to handle and can be re-used after disinfection. Due to its rounded shape and the soft synthetic coating, accidental damage of the teeth seems to be nearly impossible.


A Mediation Model for Ideas of Reference.
Ideas of reference are common in human beings, but they are frequent in certain psychopathological disorders, mainly those concerning the psychotic spectrum. The purpose of this study was to attempt to construct a model predicting the appearance of ideas of reference and to test the relationship of personality (based on the Gray model), emotional, and self-consciousness variables. Five-hundred and seventy-four participants (287 patients with several different psychopathological diagnoses) filled in the Referential Thinking Scale (REF), the GHQ-28, the Self-Consciousness Scale (SCS-R), and the SPSRQ Scale. The resulting model found full mediation of sensitivity to punishment, sensitivity to reward, depression, and public self-consciousness between anxiety and ideas of reference, regardless of the group they were in (patients vs. nonpatients). This result, based on the appearance of anxiety symptomatology, explains 43% of the variance in scores, showing the presence of ideas of reference and therefore enables prediction of a set of vulnerabilities (established with self-reports) which could lead to a psychological state of high general pathological risk and proneness to psychosis in particular.


Extraction subject-specific motor imagery time-frequency patterns for single trial EEG classification.
We introduce a new adaptive time-frequency plane feature extraction strategy for the segmentation and classification of electroencephalogram (EEG) corresponding to left and right hand motor imagery of a brain-computer interface task. The proposed algorithm adaptively segments the time axis by dividing the EEG data into non-uniform time segments over a dyadic tree. This is followed by grouping the expansion coefficients in the frequency axis in each segment. The most discriminative features are selected from the segmented time-frequency plane and fed to a linear discriminant for classification. The proposed algorithm achieved an average classification accuracy of 84.3% on six subjects by selecting the most discriminant subspaces for each one. For comparison, classification results based on an autoregressive model are also presented where the mean accuracy of the same subjects turned out to be 79.5%. Interestingly the subjects and two hemispheres of each subject are represented by distinct segmentations and features. This indicates that the proposed method can handle inter-subject variability when constructing brain-computer interfaces.


[Perceived morbidity and community burden of chikungunya in La Reunion].
Persistence of clinical manifestations, especially polyarthralgia and fatigue, is a characteristic feature of chikungunya virus (CHIK-v) infection. The purpose of this study was to measure the impact of prolonged or late-onset manifestations of CHIK-v infection on the self-perceived health of people on Reunion Island. This retrospective cohort survey, dubbed TELECHIK survey, was conducted eighteen months after the end of the chikungunya outbreak on a representative random sample from the SEROCHIK population-based survey conducted on Reunion Island. A total of 1094 subjects whose CHIK-v specific IgG antibody status had been documented were interviewed about current symptoms. Analysis of data showed 45% of CHIK+ vs 14% of CHIK- subjects reporting musculoskeletal pain (P < 0.001), 56% vs. 44% reporting fatigue (P = 0.003), 77% vs. 53% reporting cerebral manifestations (P < 0.001), 51% vs. 34% reporting sensorineural impairments (P < 0.001), 18% vs. 13% reporting digestive complaints (P = 0.06), and 38% vs. 32% reporting skin involvement (P = 0.13). The mean delay between infection and interview was two years (range, 15-34 months). Analysis of data after correction for age, gender, body mass index and comorbidity indicated that rheumatic pain, fatigue, cerebral manifestations and sensorineural impairments were more likely in CHIK+ than CHIK- subjects but the likelihood of digestive and skin manifestations was the same. With a mean delay of two years after infection, 45% to 77% of CHIK+ subjects reported prolonged or late-onset symptoms attributable to CHIK-v. These results indicate that persistent manifestations of chikungunya infection have a heavy impact on rheumatologic, neurological and sensorineural health.


Pap test use and cervical cancer incidence in First Nations women living in Manitoba.
This study examined Papanicolaou (Pap) test utilization, Pap test results, and cervical cancer incidence among First Nations (FN) women living in Manitoba, Canada taking into account age group, time period, and area of residence. Six population-based data sources were linked at an individual level. Negative binomial regression was used to compare Pap test utilization and results between FN and all other Manitoba (AOM) women. Poisson regression was used to compare cervical cancer incidence. Among women younger than 25 years, FN were more likely than AOM women to have had a Pap test [rate ratio (RR) = 1.37, 95% confidence intervals (CI), 1.22-1.53, 18-19 year olds; RR = 1.17, 95% CI, 1.05-1.31, 20-24 year olds]. There was no difference in Pap test use for women 25 to 29 or 30 to 39 years. FN 40 years and older were less likely to have a Pap test than AOM women (RR = 0.84, 95% CI, 0.75-0.93, 40-49 years old; RR = 0.71, 95% CI, 0.63-0.79, 50-59 years old; RR = 0.59, 95% CI, 0.52-0.66, 60-69 years old). FN were more likely than AOM women to have a high (RR = 1.88, 95% CI, 1.65-2.13) or low-grade Pap test result (RR = 1.60, 95% CI, 1.48-1.73). The invasive cervical cancer incidence rate was double for FN women 25 to 39 years of age (21.9 per 100,000, FN; 10.2 per 100,000, AOM, P = 0.006) and 40 to 69 years of age (24.3 per 100,000, FN; 12.3 per 100,000, AOM, P = 0.007). In conclusion, cervical cancer screening among FN women over 40 years of age must be increased to address the higher cervical cancer incidence.


Familial cerebral abscesses caused by hereditary hemorrhagic telangiectasia.
In case of a cerebral abscess without known cause, Pulmonary arteriovenous malformations (PAVM) screening should be performed. If PAVM(s) is identified, Hereditary hemorrhagic telangiectasia (HHT) is very likely and should always be considered. This case shows the benefit of familial screening for HHT and PAVM.


Phytoremediation of soil polluted by nickel using agricultural crops.
Soil pollution due to heavy metals is widespread; on the world scale, it involves about 235 million hectares. The objectives of this research were to establish the uptake efficiency of nickel by some agricultural crops. In addition, we wanted to establish also in which part of plants the metal is stored for an eventual use of biomass or for recycling the metal. The experiments included seven herbaceous crops such as: barley (Hordeum vulgaris), cabbage (Brassica juncea), spinach (Spinacea oleracea), sorghum (Sorgum vulgare), bean (Phaseolus vulgaris), tomato (Solanum lycopersicum), and ricinus (Ricinus communis). We used three levels of treatment (150, 300, and 600 ppm) and one control. At the end of the biological cycle of the crops, the different parts of plants, i.e., roots, stems, leaves, fruits, or seeds, were separately collected, oven dried, weighed, milled, and separately analysed. The leaves and stems of spinach showed a very good nickel storage capacity. The ricinus too proved to be a very good nickel storer. The ability of spinach and ricinus to store nickel was observed also in the leaves of cabbage, even if with a lower storage capacity. The bean, barley, and tomato, in decreasing order of uptake and storage capacity, showed a high concentration of nickel in leaves and stems, whereas the sorghum evidenced a lesser capacity to uptake and store nickel in leaves and stems. The bean was the most efficient in storing nickel in fruits or grains. Tomato, sorghum, and barley have shown a storage capacity notably less than bean. The bean appeared to be the most efficient in accumulating nickel in the roots, followed in decreasing order by sorghum, ricinus, and tomato. With regard to the removal of nickel, spinach was the most efficient as it contains the highest level of this metal per gram of dry matter. The ricinus, cabbage, bean, sorghum, barley, and tomato evidenced a progressively decreasing efficiency in the removal of nickel.


3D printing and milling a real-time PCR device for infectious disease diagnostics.
Diagnosing infectious diseases using quantitative polymerase chain reaction (qPCR) offers a conclusive result in determining the infection, the strain or type of pathogen, and the level of infection. However, due to the high-cost instrumentation involved and the complexity in maintenance, it is rarely used in the field to make a quick turnaround diagnosis. In order to provide a higher level of accessibility than current qPCR devices, a set of 3D manufacturing methods is explored as a possible option to fabricate a low-cost and portable qPCR device. The key advantage of this approach is the ability to upload the digital format of the design files on the internet for wide distribution so that people at any location can simply download and feed into their 3D printers for quick manufacturing. The material and design are carefully selected to minimize the number of custom parts that depend on advanced manufacturing processes which lower accessibility. The presented 3D manufactured qPCR device is tested with 20-μL samples that contain various concentrations of lentivirus, the same type as HIV. A reverse-transcription step is a part of the device's operation, which takes place prior to the qPCR step to reverse transcribe the target RNA from the lentivirus into complementary DNA (cDNA). This is immediately followed by qPCR which quantifies the target sequence molecules in the sample during the PCR amplification process. The entire process of thermal control and time-coordinated fluorescence reading is automated by closed-loop feedback and a microcontroller. The resulting device is portable and battery-operated, with a size of 12 × 7 × 6 cm3 and mass of only 214 g. By uploading and sharing the design files online, the presented low-cost qPCR device may provide easier access to a robust diagnosis protocol for various infectious diseases, such as HIV and malaria.


The non-haemostatic role of platelets in systemic lupus erythematosus.
Dysregulation of lymphocyte function, accumulation of autoantibodies and defective clearance of circulating immune complexes and apoptotic cells are hallmarks of systemic lupus erythematosus (SLE). Moreover, it is now evident that an intricate interplay between the adaptive and innate immune systems contributes to the pathogenesis of SLE, ultimately resulting in chronic inflammation and organ damage. Platelets circulate in the blood and are chiefly recognized for their role in the prevention of bleeding and promotion of haemostasis; however, accumulating evidence points to a role for platelets in both adaptive and innate immunity. Through a broad repertoire of receptors, platelets respond promptly to immune complexes, complement and damage-associated molecular patterns, and represent a major reservoir of immunomodulatory molecules in the circulation. Furthermore, evidence suggests that platelets are activated in patients with SLE, and that they could contribute to the circulatory autoantigenic load through the release of microparticles and mitochondrial antigens. Herein, we highlight how platelets contribute to the immune response and review evidence implicating platelets in the pathogenesis of SLE.


Neural layer self-assembly in geometrically confined rat and human 3D cultures.
Neurological disorders affect millions of Americans and this number is expected to rise with the aging population. Development of drugs to treat these disorders may be facilitated by improved in vitro models that faithfully reproduce salient features of the relevant brain regions. Current 3D culture methods face challenges with reliably reproducing microarchitectural features of brain morphology such as cortical or hippocampal layers. In this work, polydimethylsiloxane (PDMS) mini-wells were used to create low aspect ratio, adherent 3D constructs where neurons self-assemble into layers. Layer self-assembly was determined to depend on the size of the PDMS mini-well. Layer formation occurred in cultures composed of primary rat cortical neurons or human induced pluripotent stem cell-derived neurons and astrocytes and was robust and reproducible. Layered 3D constructs were found to have spontaneous neural activity characterized by long bursts similar to activity in the developing cortex. The responses of layered 3D cultures to drugs were more similar to in vivo data than those of 2D cultures. 3D constructs created with this method may be thus suitable as in vitro models for drug discovery for neurological disorders.


Sensitivity of ACL volume and T2∗ relaxation time to magnetic resonance imaging scan conditions.
Anterior cruciate ligament (ACL) volume and T2∗ relaxation times from magnetic resonance (MR) images have been previously shown to predict the structural properties of healing ligaments. We investigated whether MR imaging scan resolution and condition (in vivo, in situ, or ex vivo) affected ACL volume and T2∗ relaxation times in intact ligaments. ACLs of 14 pigs were imaged using a 3T scanner and a six-channel flexcoil using at least two of four possible scan conditions: (1) in vivo moderate resolution (n=14); (2) in vivo high resolution (n=7); (3) in situ high resolution acquired within 60 minutes of euthanasia (n=6); and (4) ex vivo high resolution following hind limb disarticulation and one freeze-thaw cycle (n=7). T2∗ relaxation times were mapped to the ACL voxels. The total ACL volume was then divided into four sub-volumes (Vol1-4) based on predetermined increasing ranges of T2∗ times. ACL T2∗ statistics (first quartile, median, and standard deviation (SD)) were computed. Scan resolution had no effect on the total ACL volume, but Vol1 and first quartile T2∗ times decreased with high resolution and in situ/ex vivo scan conditions. The most dramatic differences in T2∗ summary statistics were between in vivo moderate and ex vivo high resolution scan conditions that included a freeze-thaw cycle: ACL T2∗ SD increased by over 50% in 9 animals, and more than 90% in 4 animals. Our results indicated that T2∗-based prediction models to quantify in vivo structural properties of healing ligaments should be based on high resolution in vivo MR scan conditions.


Cathinones: Isotopic profiling as an aid to linking seizures.
The number of cathinone derivatives available to the street market has increased steadily since 2008. Many of these compounds have proven to be potent psychostimulants and fatalities have occurred through their recreational use. The method of manufacture is essentially the same for each cathinone, i.e., (i) selection of the appropriate β-ketoarylalkane, (ii) bromination alpha to the keto group, followed by (iii) amination using the desired amine. The cathinone derivatives are usually prepared at a very high purity and little information is available from an organic manufacturing by-products profile because the product is so pure. To provide law enforcement agencies with a tool that would enable links to be identified between samples from the same production batch, the carbon, hydrogen, and nitrogen stable isotope ratios in a number of cathinones were investigated. The aim was to determine if sufficient diversity existed in the light element stable isotope ratios of cathinones to allow the isotopic ratios to be used to discriminate between different seizures and to assist in linking samples from the same seizure. Careful measurement of the δ(13) C, δ(15) N, and δ(2) H values in each sample revealed that the stable isotope ratios for a particular cathinone analogue vary from one seizure to another. In the seizures studied, carbon, hydrogen, and nitrogen stable isotope ratios were found to vary from -32.8‰ to -26.1‰, -152‰ to +72‰, and -16.6‰ to -2.7‰, respectively. Copyright © 2015 John Wiley & Sons, Ltd.


A germ cell-specific nuclear antigen recognized by a monoclonal antibody raised against mouse testicular germ cells.
A monoclonal antibody (mAb TRA 104) raised against mouse testicular germ cells was able to recognize the nuclei of testicular germ cells at all the stages of differentiation from embryonic gonocytes to spermatids and did not react with any somatic cells. The antigen recognized by mAb TRA 104 was exclusively present in testicular extracts. The molecular weights and isoelectric point (pI) of the antigens determined by Western blotting analysis were 60-110 kDa and 7.2, respectively. This antigen(s) is referred to as a germ cell-specific nuclear antigen(s) (GENA) since GENA was first detected specifically in the genital ridge at around 12 days of gestation by Western blotting analysis. In the testis, the expression increased gradually until adulthood whereas it was lost in the ovary by postpartum day 5. Thus, GENA is a molecule(s) exclusively present in the nuclei of germ cells and may be a useful marker with which to study the mechanism of germ cell development and differentiation at the molecular level.


[Biotransformation of daidzein by resting cell system of bacterial strain isolated from bovine rumen gastric juice].
In previous study we isolated a gram-positive bacterial strain, designated Niu-O16, from bovine rumen gastric juice. The growing cells of bacterial strain Niu-O16 is capable of biotransforming isoflavone daidzein into dihydrodaidzein efficiently under anaerobic conditions. In this study we investigated the optimal bioconversion conditions for the resting cells of bacterial strain Niu-O16 to convert daidzein into dihydrodaidzein. Single factor test showed that the optimal conditions for the initial pH of phosphate buffer, the concentration of the resting cell and the concentration of the substrate daidzein were 6.0-8.0, 32-64 mg/mL (wet weight) and 0.8-1.2 mmol/L, respectively. Orthogonal experiments were used to determine the optimal combination of the resting cell concentration, substrate concentration and biotransformation time. The results showed that the optimal combination included resting cell concentration 32 mg/mL, substrate concentration 0.8 mmol/L and the biotransformation time 24 h. Furthermore, the biotransformation kinetics under optimal conditions were studied, under which conditions the highest bioconversion rate was 63.9% in the resting cell system. The results might provide information for resting cell biotransforming of anaerobes as well as its industrial application.


Engulfment of necrotic acinar cells by pancreatic stellate cells inhibits pancreatic fibrogenesis.
We have previously reported that pancreatic stellate cells (PSCs) have a phagocytic function. The aim of the present study was to investigate whether engulfment of necrotic acinar cells affects pancreatic fibrogenesis. Rat pancreatic acinar cells were incubated for 48 hours to induce necrosis, and PSCs were allowed to interact with them for 12 to 48 hours. Annexin V and propidium iodide staining or detection of DNA fragmentation was used to identify cell death. A large number of necrotic acinar cells were engulfed by PSCs. When PSCs were exposed to necrotic acinar cells for 12 hours, the number of living PSCs was significantly lower than among the control PSCs, which were not exposed to necrotic acinar cells. DNA degradation was observed in PSCs that had ingested necrotic acinar cells, and they were Annexin V and propidium iodide positive, suggesting that engulfment of necrotic acinar cells induced PSC death. There was no difference between the concentrations of transforming growth factor-beta in the medium of the PSCs that had engulfed acinar cells and the medium of the control PSCs. Engulfment of necrotic acinar cells by PSCs induces PSC death, suggesting that engulfment of necrotic acinar cells may inhibit the progression of fibrogenesis.


Hemodynamic responses during induction: comparison of Marsh and Schnider pharmacokinetic models.
Hemodynamic stability is one of the most critical concerns during induction of anesthesia. Whether the pharmacokinetic model by Marsh or the one by Schnider will produce better hemodynamic stability remains unclear. This study compared hemodynamic changes during induction between the two models. 60 patients who underwent elective surgery were randomly assigned to plasma target-controlled infusion by Marsh's (n = 30) or Schnider's (n = 30) model with an initial target concentration of 4 μg×mL-1. The target was then reset and gradually titrated to a sedation level with a narcotrend index (NI) below 64. Stroke volume, cardiac output, systemic vascular resistance, arterial pressure, target, and effect site concentration, and dose of propofol infused were recorded every minute during the first 25 minutes of infusion. Throughout the first 25 minutes, stroke volume index and cardiac index were decreased significantly in both Marsh and Schnider groups, but no statistical difference was detected between the groups (p > 0.05). Central venous pressure (CVP), systemic vascular resistance index (SVRI), and heart rate (HR) did not significantly change during induction (p > 0.05). Time to loss of responsiveness (LOR), and time for NI to decrease to 64 was faster in Marsh than in Schnider (1.51 ± 0.8 minutes vs. 2.8 ± 1.2 min, p < 0.001; 3.3 ± 2.0 minutes vs. 5.2 ± 2.3 minutes, p < 0.01, respectively). When target concentrations are titrated according to NI during induction of anesthesia, Marsh's model could induce sedation faster than Schnider's. Meanwhile, hemodynamic changes were not observed to be statistically different between the two models. Hypotension induced by plasma target-controlled infusion of propofol could mainly be attributed to decreased stroke volume instead of vascular dilation.


High-frequency magnetic oscillations evoked by posterior tibial nerve stimulation.
Magnetocephalographic recordings of the primary somatosensory response (P37m) and high-frequency oscillations (HFOs) evoked by posterior tibial nerve stimulation were obtained in normal subjects. Electrical stimuli were delivered to the posterior tibial nerve and magnetic recordings were taken over the superior aspect of the left hemisphere with a 37-channel biomagnetometer. In order to separate the high-frequency oscillations from the underlying P37m, the wide-band (0.1-1200 Hz) recorded responses were digitally filtered with a 500-800 Hz band-pass filter. The localization of the HFOs were estimated to be in somatosensory area 3b, very close to the P37m source. Our data suggest that the HFOs are somatotopically arranged in the primary somatosensory cortex, and are a ubiquitous phenomenon of the primary somatosensory cortex.


Dynamically multiplexed ion mobility time-of-flight mass spectrometry.
Ion mobility spectrometry-time-of-flight mass spectrometry (IMS-TOFMS) has been increasingly used in analysis of complex biological samples. A major challenge is to transform IMS-TOFMS to a high-sensitivity, high-throughput platform, for example, for proteomics applications. In this work, we have developed and integrated three advanced technologies, including efficient ion accumulation in an ion funnel trap prior to IMS separation, multiplexing (MP) of ion packet introduction into the IMS drift tube, and signal detection with an analog-to-digital converter, into the IMS-TOFMS system for the high-throughput analysis of highly complex proteolytic digests of, for example, blood plasma. To better address variable sample complexity, we have developed and rigorously evaluated a novel dynamic MP approach that ensures correlation of the analyzer performance with an ion source function and provides the improved dynamic range and sensitivity throughout the experiment. The MP IMS-TOFMS instrument has been shown to reliably detect peptides at a concentration of 1 nM in the presence of a highly complex matrix, as well as to provide a 3 orders of magnitude dynamic range and a mass measurement accuracy of better than 5 ppm. When matched against human blood plasma database, the detected IMS-TOF features were found to yield approximately 700 unique peptide identifications at a false discovery rate (FDR) of approximately 7.5%. Accounting for IMS information gave rise to a projected FDR of approximately 4%. Signal reproducibility was found to be greater than 80%, while the variations in the number of unique peptide identifications were <15%. A single sample analysis was completed in 15 min that constitutes almost 1 order of magnitude improvement compared to a more conventional LC-MS approach.


Diffusion-limited binding to a site on the wall of a membrane channel.
The authors develop a theory of diffusion-controlled reactions with a site located on the wall of a cylindrical membrane channel that connects two reservoirs containing diffusing particles which are trapped by the site at the first contact. An expression for the Laplace transform of the rate coefficient, kt, is derived assuming that the size of the site is small compared to the channel radius. The expression is used to find the stationary value of the rate coefficient, kinfinity, as a function of the length and radius of the channel, the radius of the site, and its position inside the channel (distances from the two ends of the channel) as well as the particle diffusion constants in the bulk and in the channel. Their derivation is based on the one-dimensional description of the particle motion in the channel, which is generalized to include binding to the site into consideration. The validity of the approximate one-dimensional description of diffusion and binding was checked by three-dimensional Brownian dynamics simulations. They found that the one-dimensional description works reasonably well when the size of the site does not exceed 0.2 of the channel radius.


Evaluation of a membrane filtration method for the rapid enumeration of confirmed Clostridium perfringens from water.
A modification of the UK reference and ISO 14189 TSCA medium for the enumeration of Clostridium perfringens from water coupled with a membrane filter transfer technique for testing for production of acid phosphatase was evaluated. The new tryptose cycloserine agar (TCA) medium, which lacks sodium metabisulphite but contains sodium pyruvate to improve recovery, allows the isolation and confirmation of Cl. perfringens within 18-24 h of sample processing. Data from a multilaboratory study analysed according to ISO 17994 showed that TCA was equivalent to TSCA for the enumeration of Cl. perfringens. The identification of acid phosphatase-negative isolates revealed a false-negative rate for the TCA method of 0.8%. The TCA membrane filter transfer procedure provides confirmed Cl. perfringens counts in half the time of the TSCA method and is simple to undertake. The testing of drinking water for Clostridium perfringens is a regulatory parameter in Europe and the UK. Current UK and ISO methods employ membrane filtration (MF) and TSCA medium followed by subculture and confirmation of isolates by testing for acid phosphatase. This takes 48 h. We present here the results of a multilaboratory evaluation of a MF method that features a simplified isolation medium (TCA) and a membrane transfer procedure for the acid phosphatase test resulting in confirmed results being available in 18-24 h. This development significantly reduces the time to confirmed results for Cl. perfringens from water samples.


Comparison and Elucidation of Structural Diversity and Variation of G-Rich Sequences with a Single G-Base Difference.
Previously, we found the structural diversity of a mitochondrial sequence mt10251 (GGGTGGGAGTAGTTCCCTGCTAAGGGAGGG), including coexistence of a hairpin structure and monomeric, dimeric, and tetrameric G4 structures in 20 mM K+ solution. Moreover, a single-base mutation of mt10251 could cause significant changes in terms of structural populations and polymorphism. In this work, we investigate the diverse G4 topologies of mt10251 and structural variation of its mutants. Using circular dichroism (CD), nuclear magnetic resonance (NMR), and polyacrylamide gel electrophoresis (PAGE), we first illustrate an unusual tetrameric G4 structure together with hairpin bulges formed by four strands of mt10251-d30 (GGGTGGGAGTAGTTCCCTGCTAAGGGAGG). Of interest is that the structural conversion from a hairpin structure to diverse G4 structures in mt10251 is negligible in mt10251-d30 after the addition of 20 mM K+. Further kinetic and thermal studies of mt10251, mt10251-d30, and their mutants reveal the major factors in determining the transition from a hairpin structure to diverse G4 structures of mt10251 and the structural variation of their mutants after the addition of 20 mM K+.


A substrate-independent approach for bactericidal surfaces.
Existing methods for imparting antibacterial performance to solid surfaces tend to either be substrate-specific or rely upon leaching modes of action that cause ecological damage. An alternative approach is outlined comprising plasmachemical functionalization of solid surfaces with poly(4-vinyl pyridine) moieties and their subsequent activation (quaternization) with bromobutane to yield bactericidal activity. These bioactive surfaces can be applied to a host of different substrate materials and are easily regenerated by rinsing in water.


Ultrastructural localization of E-cadherin cell adhesion molecule on the cytoplasmic membrane of keratinocytes in vivo and in vitro.
We examined the ultrastructural localization of E (epithelial)-cadherin cell adhesion molecules by immunoperoxidase electron microscopy on the epithelium of mouse intestine, epidermis of human skin, and cultured human keratinocytes. The in vivo studies demonstrated that E-cadherin was present at the intermediate junction but not at the desmosome of the mouse intestinal single epithelium, and was found on the cytoplasmic membranes of keratinocytes with condensation in the intercellular space of the desmosomes, except for the basal surface of the basal cells. In vitro studies demonstrated that keratinocytes cultured in medium containing a low Ca2+ concentration (0.1 mM) lacked the tight connection through desmosomes, and that E-cadherin showed diffuse distribution and dot-like accumulation around the free surface of the cytoplasmic membrane. In culture medium containing a high concentration of Ca2+ (0.6 mM), keratinocytes formed desmosomal adhesion structures in which E-cadherin was accumulated. The free surface of the keratinocytes in this medium showed weaker distribution and a lesser amount of dot-like accumulation of E-cadherin than that in a low Ca2+ condition. These findings suggest that the distribution pattern of the E-cadherin cell adhesion molecules on the keratinocytes is different from that on the single epithelium of the intestine, and that E-cadherin on the cytoplasmic membrane of the keratinocytes shifts to the desmosomes under physiological conditions, participating in adhesion in association with other desmosomal cadherins.


Role of liver endothelial and Kupffer cells in clearance of human C1q in rats.
In the present study the contribution of rat liver endothelial cells (EC) and Kupffer cells (KC) in the clearance of human (hu) C1q in rats was investigated. In untreated rats and rats depleted from KC the clearance kinetics and the tissue distribution of hu C1q were measured. In untreated rats, the clearance of hu C1q occurred in a monophasic manner with a half-life of 66 +/- 26.7 min. The clearance of hu C1q in KC-depleted rats was delayed significantly (p < 0.001) and occurred with a half-life of 217 +/- 78.8 min. Fifteen min after injection, 11 +/- 3.5% of hu C1q was found in the liver of untreated rats and 8 +/- 1.4% was found in the liver of KC-depleted rats. The percentage non-trichloroacetic acid precipitable activity in the circulation, as a measure for degradation of C1q, reached a level of 11.6 +/- 5.6% at 240 min in untreated rats compared with 4.6 +/- 5.8% in KC-depleted rats. Double immunofluorescence staining 5 min after administration of C1q in untreated rats, revealed that C1q was associated with KC and EC in the liver. Fifteen minutes after i.v. injection of hu C1q, there was an uptake of C1q in the hepatocytes. In KC-depleted rats, 5 min after administration of hu C1q, C1q was bound to the EC. Fifteen minutes after injection, C1q was also found in the hepatocytes. Electron microscopical studies revealed that C1q binds to EC, and that it is internalized in the hepatocytes and KC. The clearance of hu C1q in untreated rats was inhibited by preadministration of high concentrations of bovine C1q. These data show that rats depleted from KC are able to bind, internalize and degrade C1q, and that EC may play a role in the handling of C1q and C1q bound to immune complexes.


Maintenance of surrogate light chain expression induces developmental delay in early B cell compartment.
The production of a mature B cell requires passage through a number of developmental checkpoints. The pre-BCR plays a critical role in passage through the pro-B cell/pre-B cell checkpoint, and thus plays a central role in regulating the differentiation of a B cell. Due to the significance of this receptor, it is imperative that pre-BCR expression and function are precisely regulated. In this study, we have investigated a system in which the regulation of the pre-BCR is altered. We have found that continued expression of components of the pre-BCR (lambda5) resulted in a delay in the kinetics of B cell maturation. Pro-B cells from normal mouse bone marrow retrovirally infected with lambda5 exhibited a delay in differentiation. As compared with wild-type cells at the same time point, there is a reduction in the presence of cell surface markers that indicate developmental progression, and there is a 6- to 16-fold decrease in the production of Ig-positive cells in B cell maturation assays. The capacity to alter B cell progression by modifying and extending pre-BCR expression argues that the receptor and its associated signals play a unique role in directing developmental outcomes.


Fate of the distal aorta following root replacement in Marfan syndrome: a propensity score matched study.
The aortic root is the most frequent segment involved in Marfan syndrome. However, Marfan syndrome is a systemic hereditary connective tissue disorder, and knowledge regarding the outcomes of the native distal aorta after prophylactic aortic root surgery is limited. From April 2010 to December 2020, 226 patients with Marfan syndrome and 1,200 patients without Marfan syndrome who underwent Bentall procedures were included in this study. By propensity score matching, 134 patients were assigned to each group. Clinical manifestations and follow-up data were acquired from hospital records and telephone contact. The cumulative incidence of aortic events was estimated in Marfan and non-Marfan patients with death as a competing risk. Patients with and without Marfan syndrome had similar baseline characteristics after propensity score matching. Differences in the aortic root (62.25 ± 11.96 vs. 54.03 ± 13.76, P < .001) and ascending aorta (37.71 ± 9.86 vs. 48.16 ± 16.01, P < .001) remained after matching. No difference was observed in the frequency of aortic adverse events between the two groups (10.5% vs. 4.6%, P = 0.106). The cumulative incidence of aortic events was not different between Marfan and non-Marfan patients (15.03% ± 4.72% vs. 4.18% ± 2.06%, P = 0.147). Multivariate Cox regression indicated no significant impact of Marfan syndrome on distal aortic events (HR: 1.172, 95% CI: 0.263-5.230, P = 0.835). Descending and abdominal aortic diameter above normal at the initial procedure were associated with the risk of distal aortic events (HR: 20.735, P = .003, HR: 22.981, P = .002, respectively). New-onset events of the residual aorta in patients undergoing Bentall procedures between the Marfan and non-Marfan groups were not significantly different. Distal aortic diameter above normal at initial surgery was associated with a higher risk of adverse aortic events.


Temporary arrest of fetal movement with pancuronium bromide to enable antenatal magnetic resonance imaging of holoprosencephaly.
The well-known ability of real-time ultrasound to detect congenital abnormalities is often limited by acoustic artifact or fetal position or both. Magnetic resonance imaging can provide superior soft tissue resolution but is vulnerable to maternal and fetal motion artifact. Described and illustrated here is a case of fetal holoprosencephaly that was not of diagnostic clarity on ultrasound. The fetus was paralyzed with an intramuscular injection of pancuronium bromide before a resonance imaging study. Successful fetal paralysis with pancuronium bromide has been reported prior to a variety of fetal interventions for the temporary arrest of fetal movement. The resonance study illustrated here was of significantly superior clarity and improved the accuracy of prognosis and management counseling. It is concluded that in selected cases where ultrasound is not of diagnostic clarity due to acoustic artifact, fetal paralysis and magnetic resonance imaging may be considered.


Periferic intravenous infusion of fenoldopam through an elastomeric pump.
Fenoldopam has been used to protect renal function in critically ill patients and in those undergoing major surgery, where a possible damage of kidney is expected. Numerous randomized studies and meta-analysis demonstrated the efficacy of fenoldopam in this setting. We performed this study to demonstrate the feasibility of administering fenoldopam, trough an elastomeric pump connected to a peripheral vein, to patients undergoing nephron sparing surgery. Twenty consecutive patients, ASA physical status class I-III, undergoing laparoscopic or laparotomic renal tumorectomy were enrolled. Fenoldopam was infused trough an elastomeric pump at a fixed dosage of 0.1 mcg/kg/min, obtained after diluting the drug with saline solution according to the weight of the patient. We injected the drug trough a peripheral vein from the induction of anaesthesia for 48 hours after the end of surgery. The infusion of fenoldopam did not modify the haemodynamic parameters. We did not find episodes of hypotension and only in three patients we registered episodes of tachycardia, not requiring the suspension of the infusion. No other side-effect was noted. The administration of fenoldopam, trough an elastomeric pump, in patients undergoing renal tumorectomy is feasible through a peripheral vein access.


GENETIC DIFFERENTIATION AND HETEROZYGOSITY IN PINYON PINE ASSOCIATED WITH RESISTANCE TO HERBIVORY AND ENVIRONMENTAL STRESS.
Arizona's Sunset Crater began erupting in 1064 AD and for the next 200 years buried over 2,000 km2 in ash, cinders, and lava. Soil analyses indicate that pinyon pines (Pinus edulis) currently colonizing the cinder fields are faced with a highly stressful environment. Many of these pinyons suffer chronic, intense insect herbivory that reduces plant growth and eliminates female cone production. In contrast, herbivory among pinyons growing in neighboring sandy-loam soils is minimal. Furthermore, numerous trees within the heavily infested cinder field population suffer relatively low herbivory and maintain normal growth and reproduction. We used four polymorphic enzymes to examine the relationship between herbivore attack, environmental stress and genotypes of the adjacent cinder field, and sandy-loam soil pinyon populations. Our results demonstrate that 1) resistant trees display significant genetic differences and are more heterozygous for two enzymes associated with herbivory than susceptible trees; and 2) the cinder-soil pinyons exhibit significant genetic differences and are more heterozygous for an enzyme associated with environmental stress than the neighboring sandy-loam soil pinyons. We conclude that heterozygosity of specific or closely linked loci may facilitate pinyon resistance to herbivory and environmental stress, and that strong selection across narrow geographic boundaries resulted in rapid genetic differentiation of pinyon populations.


Hypertrophic Olivary Degeneration and Palatal or Oculopalatal Tremor.
Hypertrophic degeneration of the inferior olive is mainly observed in patients developing palatal tremor (PT) or oculopalatal tremor (OPT). This syndrome manifests as a synchronous tremor of the palate (PT) and/or eyes (OPT) that may also involve other muscles from the branchial arches. It is associated with hypertrophic inferior olivary degeneration that is characterized by enlarged and vacuolated neurons, increased number and size of astrocytes, severe fibrillary gliosis, and demyelination. It appears on MRI as an increased T2/FLAIR signal intensity and enlargement of the inferior olive. There are two main conditions in which hypertrophic degeneration of the inferior olive occurs. The most frequent, studied, and reported condition is the development of PT/OPT and hypertrophic degeneration of the inferior olive in the weeks or months following a structural brainstem or cerebellar lesion. This "symptomatic" condition requires a destructive lesion in the Guillain-Mollaret pathway, which spans from the contralateral dentate nucleus via the brachium conjunctivum and the ipsilateral central tegmental tract innervating the inferior olive. The most frequent etiologies of destructive lesion are stroke (hemorrhagic more often than ischemic), brain trauma, brainstem tumors, and surgical or gamma knife treatment of brainstem cavernoma. The most accepted explanation for this symptomatic PT/OPT is that denervated olivary neurons released from inhibitory inputs enlarge and develop sustained synchronized oscillations. The cerebellum then modulates/accentuates this signal resulting in abnormal motor output in the branchial arches. In a second condition, PT/OPT and progressive cerebellar ataxia occurs in patients without structural brainstem or cerebellar lesion, other than cerebellar atrophy. This syndrome of progressive ataxia and palatal tremor may be sporadic or familial. In the familial form, where hypertrophic degeneration of the inferior olive may not occur (or not reported), the main reported etiologies are Alexander disease, polymerase gamma mutation, and spinocerebellar ataxia type 20. Whether or not these are associated with specific degeneration of the dentato-olivary pathway remain to be determined. The most symptomatic consequence of OPT is eye oscillations. Therapeutic trials suggest gabapentin or memantine as valuable drugs to treat eye oscillations in OPT.


Total intravenous anesthesia with propofol for thymectomy in a patient with myasthenia gravis.
Experience with the use of propofol for induction and maintenance of anesthesia in patients with myasthenia gravis is limited. This case report documents the safe use of propofol in a patient with myasthenia gravis. Because of its unique pharmacodynamic and pharmacokinetic profile, propofol may be an ideal agent for safe use in the young patient with myasthenia gravis.


Identification of side population cells in human lung adenocarcinoma A549 cell line and elucidation of the underlying roles in lung cancer.
The present study aimed to isolate and characterize side population (SP) cells in the human lung cancer A549 cell line, and elucidate the molecular mechanism of SP cells underlying lung cancer. The SP and non-SP (NSP) cells in A549 cells were isolated and their differentiation was analyzed by fluorescence-activated cell sorting. An in vitro plate clone assay, Matrigel® Transwell assay and chemoresistance analysis of the sorted SP and NSP cells were performed. In addition, the sorted SP and NSP cells were injected into BALB/c nude mice to detect their tumorigenic potential in vivo. The expression of ATP-binding cassette sub-family G member 2 (ABCG2) in transplanted tumors was detected by immunohistochemistry. The SP and NSP cells were successfully isolated. The results demonstrated that SP cells accounted for 1.09% of live A549 cells. SP cells produced SP and NSP cells, while NSP cells only produced NSP cells. In addition, SP cells formed more colonies, exhibited improved invasive ability and increased levels of chemoresistance compared with NSP cells in vitro. SP cells demonstrated a higher tumorigenic potential in BALB/c nude mice, and the number of ABCG2-positive cells in the SP xenograft tumors were significantly increased compared with that in the NSP xenograft tumors. The present study indicated that SP cells isolated from the human lung cancer A549 cell line demonstrated increased tumorigenicity, and improved invasive ability and chemoresistance compared with NSP cells. In addition, detection of ABCG2 expression may assist in predicting the chemotherapeutic outcome of patients, and serve as a target for treating lung cancer.


Four monoclonal immunoglobulins in a patient with chronic lymphocytic leukemia.
We report here the case of a 73-year-old woman with chronic lymphocytic leukemia. Two years after the diagnosis, electrophoresis of her serum showed two monoclonal fractions, but our modified immunofixation procedure revealed four monoclonal immunoglobulins in five fractions: two IgG lambda fractions, one IgG kappa fraction, one IgA kappa fraction, and one IgG kappa fraction. This is an exceptionally high number of monoclonal immunoglobulins in a single patient. In the course of her disease the patient did not show any clinical, radiological, or laboratory signs of multiple myeloma or macroglobulinemia. The different monoclonal immunoglobulins were considered to be one expression of her B-lymphocytic malignancy.


Effects of Aqueous Extract of Lycopersicum esculentum L. var. "Camone" Tomato on Blood Pressure, Behavior and Brain Susceptibility to Oxidative Stress in Spontaneously Hypertensive Rats.
Behavioral disorders affect millions of people worldwide. Hypertension contributes to both the development and progression of brain damage and cognitive dysfunction and could represent the most powerful modifiable risk factor for cerebral vessel dysfunction and consequent behavioral impairment. Tomato contains antioxidants and bioactive molecules that might play an important role in the prevention of cardiovascular and brain diseases. The effects of the combined gel and serum from Lycopersicum esculentum L. var. "Camone" tomatoes and those of purified tomato glycoalkaloids (tomatine) and an antihypertensive drug (captopril) were investigated in male spontaneously hypertensive rats (SHRs) and compared with normotensive Wistar Kyoto (WKY) rats. Body weight, systolic blood pressure, behavioral parameters, as well as brain susceptibility to oxidative stress and brain cytokine contents, were assessed. Treating hypertensive rats with tomato gel/serum or captopril for four weeks caused a significant reduction in blood pressure, decreased locomotor activity and increased grooming behavior; the last two parameters were also significantly affected by tomatine treatment. Brain slices obtained from hypertensive rats treated with tomato gel/serum were more resistant to oxidative stress and contained lower levels of inflammatory cytokines than vehicle-treated ones. In contrast, tomatine treatment had no effect. In conclusion, the tomato-derived gel/serum can be considered a dietary supplement able to drive in vivo blood pressure towards healthier values and also control some central effects such as behavior and brain oxidative stress.


A new species of Oileus Kaup (Coleoptera, Passalidae) from Guatemala, with a key to the species of the genus.
Oileus gasparilomisp. n. is described from nine specimens from the mountains of Quiché in Guatemala, from cloud forest at 1795 m elevation. This represents the second species of the genus for Guatemala, differing from the closely related Mexican species Oileus rimator (Truqui) in having a straight anterior clypeal border, the postocular sulcus divided by a keel and the pronotum almost straight (not clearly bilobed). A key to the species of Oileus is given.


Characterization of immunomodulatory activities of honey glycoproteins and glycopeptides.
Recent evidence suggests an important role for natural honey in modulating immune response. To identify active components responsible, this study investigated the immunomodulatory properties of glycoproteins and glycopeptides fractionated from Ziziphus honey. Honey proteins/peptides were fractionated by size exclusion chromatography into five peaks with molecular masses in the range of 2-450 kDa. The fractionated proteins exhibited potent, concentration-dependent inhibition of reactive oxygen species production in zymosan-activated human neutrophils (IC50 = 6-14 ng/mL) and murine macrophages (IC50 = 2-9 ng/mL). Honey proteins significantly suppressed the nitric oxide production by LPS-activated murine macrophages (IC50 = 96-450 ng/mL). Moreover, honey proteins inhibited the phagocytosis latex bead macrophages. The production of pro-inflammatory cytokines IL-1β and TNF-α by human monocytic cell line in the presence of honey proteins was analyzed. Honey proteins did not affect the production of IL-1β; however, TNF-α production was significantly suppressed. These findings indicated that honey glycoproteins and glycopeptides significantly interfere with molecules of the innate immune system.


The Remarkable Amphoteric Nature of Defective UiO-66 in Catalytic Reactions.
One of the major requirements in solid acid and base catalyzed reactions is that the reactants, intermediates or activated complexes cooperate with several functions of catalyst support. In this work the remarkable bifunctional behavior of the defective UiO-66(Zr) metal organic framework is shown for acid-base pair catalysis. The active site relies on the presence of coordinatively unsaturated zirconium sites, which may be tuned by removing framework linkers and by removal of water from the inorganic bricks using a dehydration treatment. To elucidate the amphoteric nature of defective UiO-66, the Oppenauer oxidation of primary alcohols has been theoretically investigated using density functional theory (DFT) and the periodic approach. The presence of acid and basic centers within molecular distances is shown to be crucial for determining the catalytic activity of the material. Hydrated and dehydrated bricks have a distinct influence on the acidity and basicity of the active sites. In any case both functions need to cooperate in a concerted way to enable the chemical transformation. Experimental results on UiO-66 materials of different defectivity support the theoretical observations made in this work.


Quantitative determination of localized tissue oxygen concentration in vivo by two-photon excitation phosphorescence lifetime measurements.
This study describes the use of two-photon excitation phosphorescence lifetime measurements for quantitative oxygen determination in vivo. Doubling the excitation wavelength of Pd-porphyrin from visible light to the infrared allows for deeper tissue penetration and a more precise and confined selection of the excitation volume due to the nonlinear two-photon effect. By using a focused laser beam from a 1,064-nm Q-switched laser, providing 10-ns pulses of 10 mJ, albumin-bound Pd-porphyrin was effectively excited and oxygen-dependent decay of phosphorescence was observed. In vitro calibration of phosphorescence lifetime vs. oxygen tension was performed. The obtained calibration constants were kq = 356 Torr(-1) x s(-1) (quenching constant) and tau0 = 550 micros (lifetime at zero-oxygen conditions) at 37 degrees C. The phosphorescence intensity showed a squared dependency to the excitation intensity, typical for two-photon excitation. In vivo demonstration of two-photon excitation phosphorescence lifetime measurements is shown by step-wise PO2 measurements through the cortex of rat kidney. It is concluded that quantitative oxygen measurements can be made, both in vitro and in vivo, using two-photon excitation oxygen-dependent quenching of phosphorescence. The use of two-photon excitation has the potential to lead to new applications of the phosphorescence lifetime technique, e.g., noninvasive oxygen scanning in tissue at high spatial resolution. To our knowledge, this is the first report in which two-photon excitation is used in the setting of oxygen-dependent quenching of phosphorescence lifetime measurements.


Bilateral latero-pontine infarction: a rare syndrome, an unusual imaging.
The authors present one case of bilateral infarction of the brain stem, in the territory of the antero-inferior cerebellar artery. Besides the fact that such bilateral ischaemic lesions are rare, the initial clinical presentation mimicking a vestibular neuronitis indicates that this latero-pontine syndrome may appear as a peripheral disorder. It also reminds clinicians that careful and repeated examinations should always be performed in all patients suffering from vertigo. An unusual iconography is also presented.


Communication skills in blind children: a preliminary investigation.
There are anecdotal reports that blind children sometimes use language inappropriately, but there has been no recent systematic investigation of the communication skills of children with congenital blindness. The aim of the present study was to conduct a preliminary investigation of the communication skills of a group of children with congenital blindness. The parents of eight congenitally blind children completed the Children's Communication Checklist-2. The checklist ratings showed that the communication profiles of a large proportion of the group warranted clinical investigation or were indicative of a communication disorder. The results from this preliminary investigation support the need for a larger study on the communication skills of children with congenital blindness.


Nonpeptide alphavbeta3 antagonists. 8. In vitro and in vivo evaluation of a potent alphavbeta3 antagonist for the prevention and treatment of osteoporosis.
3(S)-(6-methoxypyridin-3-yl)-3-[2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)propyl]imidazolidin-1-yl]propionic acid 6 was identified as a potent and selective antagonist of the alpha(v)beta(3) receptor. This compound has an excellent in vitro profile (IC(50) = 0.08 nM), a significant unbound fraction in human plasma (12%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in three in vivo models of bone turnover, the compound was selected for clinical development. To support the ongoing metabolism and safety studies, a novel strategy was employed in which a series of oxidized derivatives of 6 were prepared by exposure of 6 (or the methyl ester) to chemical oxidizing agents. These products proved useful in the identification of active metabolites generated by either in vitro or in vivo metabolism.


Porcine liver succinyltrialanine p-nitroanilide hydrolytic enzyme. Its purification and characterization as a post-proline cleaving enzyme.
Succinyltrialanine p-nitroanilide(STANA)-hydrolytic enzyme was purified 5,200-fold from porcine liver soluble fraction with a yield of 75% by ammonium sulfate fractionation and chromatographies on DEAE-Sephacel, Sephadex G-150, and hydroxylapatite columns. The purified enzyme was homogeneous as judged by polyacrylamide gel electrophoresis in the presence and absence of sodium dodecyl sulfate (SDS). The pI of the enzyme was 4.9 by dis gel electrofocusing and the molecular weight was calculated to be 72,000 by gel filtration on a Sephadex G-150 column and 74,000 by SDS-polyacrylamide gel electrophoresis. Acidic amino acids amounted to 17.2% of the total amino acid residues, and the basic ones, 12.9%. No hexosamine was detected. The STANA-hydrolytic enzyme showed maximal activity at pH 7.4 against succinyltrialanine p-nitroanilide and at pH 6.5 against succinyl-Gly-Pro-4-methylcoumaryl 7-amide (MCA), and was stable between pH 6 and 7 in the presence of dithiothreitol. This enzyme hydrolyzed succinyl-Gly-Pro-Leu-Gly-Pro-MCA, succinyl-Gly-Pro-MCA, succinyl-Ala-Pro-Ala-MCA, and several proline-containing natural peptides in addition to succinyltrialanine p-nitroanilide, but was unable to hydrolyze the substrates of aminopeptidases, dipeptidylaminopeptidase IV, trypsin, and chymotrypsin. Elastatinal and chymostatin were effective inhibitors and their IC50 values were 8.7 micrograms/ml and 18.2 micrograms/ml, respectively. The enzyme was completely inhibited by 10(-7) M p-chloromercuribenzoic acid (pCMB), 10(-7) M p-chloromercuriphenylsulfonic acid (pCMPS), and 10(-4) M diisopropyl phosphofluoridate (DFP), but not by 1 mM E-64, which is known as an inhibitor specific to thiol proteinase. The enzyme was easily inactivated by agitation in a Vortex mixer, and its activity was recovered by the addition of thiol compounds such as dithiothreitol, 2-mercaptoethanol and cysteine. The effects of inhibitors and thiol compounds were substantially identical when the enzyme activity was measured with either succinyltrialanine p-nitroanilide or succinyl-Gly-Pro-MCA as a substrate. These results indicate that the STANA-hydrolytic enzyme in the liver soluble fraction is a post-proline cleaving enzyme [EC 188.8.131.52].


[Diagnosis of perforation of the kidney pelvis using sonography].
In a case report the diagnostics of a perforation of the renal pelvis using ultrasound is presented. Spontaneous urinary extravasations of the renal pelvis may appear in a previously diseased urinary tract also without the diuretic effect of contrast media. The ultrasound examination show the perirenal fluid collections and the diagnosis of spontaneous perforation of the renal pelvis is stated together with the clinical course.


Cytoarchitectonic mapping of the human frontal operculum-New correlates for a variety of brain functions.
The human frontal operculum (FOp) is a brain region that covers parts of the ventral frontal cortex next to the insula. Functional imaging studies showed activations in this region in tasks related to language, somatosensory, and cognitive functions. While the precise cytoarchitectonic areas that correlate to these processes have not yet been revealed, earlier receptorarchitectonic analysis resulted in a detailed parcellation of the FOp. We complemented this analysis by a cytoarchitectonic study of a sample of ten postmortem brains and mapped the posterior FOp in serial, cell-body stained histological sections using image analysis and multivariate statistics. Three new areas were identified: Op5 represents the most posterior area, followed by Op6 and the most anterior region Op7. Areas Op5-Op7 approach the insula, up to the circular sulcus. Area 44 of Broca's region, the most ventral part of premotor area 6, and parts of the parietal operculum are dorso-laterally adjacent to Op5-Op7. The areas did not show any interhemispheric or sex differences. Three-dimensional probability maps and a maximum probability map were generated in stereotaxic space, and then used, in a first proof-of-concept-study, for functional decoding and analysis of structural and functional connectivity. Functional decoding revealed different profiles of cytoarchitectonically identified Op5-Op7. While left Op6 was active in music cognition, right Op5 was involved in chewing/swallowing and sexual processing. Both areas showed activation during the exercise of isometric force in muscles. An involvement in the coordination of flexion/extension could be shown for the right Op6. Meta-analytic connectivity modeling revealed various functional connections of the FOp areas within motor and somatosensory networks, with the most evident connection with the music/language network for Op6 left. The new cytoarchitectonic maps are part of Julich-Brain, and publicly available to serve as a basis for future analyses of structural-functional relationships in this region.