Macromonomers as a Novel Way to Investigate and Tailor Silicon-Oxycarbide-Based Materials Obtained from Polymeric Preceramic Precursors.
It has been shown that bifunctional monomers (D units), which are used to increase the carbon content in silicon oxycarbide precursors, can form volatile oligomers, thus affecting the amount of carbon available during the transition into the final material in the annealing process. Additionally, an uneven distribution of carbon-rich mers may lead to the formation of a free-carbon phase, instead of the incorporation of carbon atoms into the silicon matrix. In this study, a novel two-step approach was utilized. Firstly, a macromonomer containing a number of structural units with precise structure was synthesized, which was later polycondensed into a ceramic precursor. Chlorodimethylsilane modified 2,4,6,8-tetramethylcyclotetrasiloxane was used as a silicon oxycarbide precursor monomer containing both T and D structural units (i.e., silicon atoms bonded to three and two oxygen atoms, respectively), with well-defined interconnections between structural units. Such a macromonomer prevents the formation of small siloxane rings, and has a very limited number of possible combinations of structural units neighboring each silicon atom. This, after investigation using IR, XRD, TG and elemental analysis, gave insight into the effect of "anchoring" silicon atoms bonded to two methyl groups, as well as the impact of their distribution in comparison to the materials obtained using simple monomers containing a single silicon atom (structural unit).


Glucosinolate uptake by developing rapeseed embryos.
Embryos excised from the seed of rapeseed (Brassica napus L.) accumulated glucosinolate from the culture medium. Uptake was saturable, subject to inhibition, varied with the developmental stage of the embryo but correlated with the time of accumulation of glucosinolates in situ. It is suggested that a carrier-mediated transport system is operating in the developing embryo.


Molecular modeling on structure-function analysis of human progesterone receptor modulators.
Considering the significance of progesterone receptor (PR) modulators, the present study is explored to envisage the biophoric signals for binding to selective PR subtype-A using ligand-based quantitative structure activity relationship (QSAR) and pharmacophore space modeling studies on nonsteroidal substituted quinoline and cyclocymopol monomethyl ether derivatives. Consensus QSAR models (Training set (Tr): n(Tr)=100, R(2) (pred)=0.702; test set (Ts): n(Ts)=30, R(2) (pred)=0.705, R(2) (m)=0.635; validation set (Vs): n(Vs)=40, R(2) (pred)=0.715, R(2) (m)=0.680) suggest that molecular topology, atomic polarizability and electronegativity, atomic mass and van der Waals volume of the ligands have influence on the presence of functional atoms (F, Cl, N and O) and consequently contribute significant relations on ligand binding affinity. Receptor independent space modeling study (Tr: n(Tr)=26, Q(2)=0.927; Ts: n(Ts)=60, R(2) (pred)=0.613, R(2) (m)=0.545; Vs: n(Vs)=84, R(2) (pred)=0.611, R(2) (m)=0.507) indicates the importance of aromatic ring, hydrogen bond donor, molecular hydrophobicity and steric influence for receptor binding. The structure-function characterization is adjudged with the receptor-based docking study, explaining the significance of the mapped molecular attributes for ligand-receptor interaction in the catalytic cleft of PR-A.


[Survey regarding mental health conditions of high school students and attitudes of students and their teachers toward students' mental health issues].
We administered a self-reporting questionnaire survey regarding the mental health conditions of high school students and attitudes of students and their teachers toward students' mental health issues. In addition, we discussed the requirements for high school students' mental health support system. The subjects were 3,312 students and 208 teachers in four Shizuoka prefectural public high schools in 2009. University Personality Inventory (UPI) is usually conducted to assess university students' mental state and is a questionnaire that high school students can answer easily. Therefore, we adopted UPI for this survey. UPI was composed of 56 unhealthy and 4 healthy condition items. High school students completed the UPI and determined the sum of unhealthy condition items; a higher score indicated a poorer mental health status. The average UPI score of all students (n = 3,312) was 12.7 points, and that of females (n = 1,217)was 15.2 points, which was significantly higher than the 11.3 points of males (n = 2,095). Those with scores > or = 30 points (7.5%), which was more than half of the maximum score, were designated as the High Score (HS) group and considered to have poor mental health. Those with scores of > or = 40 (1.4%) seemed to have very poor mental health, and there was concern that they may be suffering from psychosis. Our observations indicated that HS students were likely to avoid seeking help regarding mental health issues, which was especially true for male HS students. The majority of students chose their friends and parents as advisers, but HS students were significantly more likely to choose advisers who were engaged in jobs related to medical work. Students in both the HS and non-HS groups who did not wish to consult anyone else about their mental conditions wanted to be approached by those around them. High school teachers hesitated to intervene with mentally disturbed students and attempted to resolve problems within the school. Thus, it appears necessary for families, school teachers, and psychiatrists to build closer relations with each other to promote mental health among high school students.


Mechanism of activation of protein kinase D2(PKD2) by the CCK(B)/gastrin receptor.
Recently, we cloned a novel serine/threonine kinase termed protein kinase D2 (PKD2). PKD2 can be activated by phorbol esters both in vivo and in vitro but also by gastrin via the cholecystokinin/CCK(B) receptor in human gastric cancer cells stably transfected with the CCK(B)/gastrin receptor (AGS-B cells). Here we identify the mechanisms of gastrin-induced PKD2 activation in AGS-B cells. PKD2 phosphorylation in response to gastrin was rapid, reaching a maximum after 10 min of incubation. Our data demonstrate that gastrin-stimulated PKD2 activation involves a heterotrimeric G alpha(q) protein as well as the activation of phospholipase C. Furthermore, we show that PKD2 can be activated by classical and novel members of the protein kinase C (PKC) family such as PKC alpha, PKC epsilon, and PKC eta. These PKCs are activated by gastrin in AGS-B cells. Thus, PKD2 is likely to be a novel downstream target of specific PKCs upon the stimulation of AGS-B cells with gastrin. Our data suggest a two-step mechanism of activation of PKD2 via endogenously produced diacylglycerol and the activation of PKCs.


Tuning the Liquid-Liquid Transition by Modulating the Hydrogen-Bond Angular Flexibility in a Model for Water.
We propose a simple extension of the well known ST2 model for water [F. H. Stillinger and A. Rahman, J. Chem. Phys. 60, 1545 (1974)] that allows for a continuous modification of the hydrogen-bond angular flexibility. We show that the bond flexibility affects the relative thermodynamic stability of the liquid and of the hexagonal (or cubic) ice. On increasing the flexibility, the liquid-liquid critical point, which in the original ST2 model is located in the no-man's land (i.e., the region where ice is the thermodynamically stable phase) progressively moves to a temperature where the liquid is more stable than ice. Our study definitively proves that the liquid-liquid transition in the ST2 model is a genuine phenomenon, of high relevance in all tetrahedral network-forming liquids, including water.


Glucose utilization and the PI3-K pathway: mechanisms for cell survival in preimplantation embryos.
The maintenance of optimal glucose utilization during the preimplantation period is critical for embryo survival. A decrease in glucose transport during preimplantation development has been linked to the early steps of programmed cell death in these embryos. Decreased glucose transport is not thought to be simply a consequence of cell death, rather it is thought to be a trigger that can initiate the apoptotic cascade. Extensive apoptosis during the preimplantation period may manifest later in pregnancy as a malformation-- or miscarriage, if cell loss is excessive. Phosphatidylinositol 3-kinase (PI3-K) is a known regulator of a number of physiologic responses including cellular proliferation, growth, and survival as well as glucose metabolism. Studies performed in other cell systems have demonstrated that the PI3-K pathway plays a critical role in maintaining glucose transport and metabolism. This review will present the current evidence that suggests that PI3-K is vital for preimplantation embryo survival and development. In addition, data demonstrating that PI3-K activity is important for glucose metabolism during this early developmental period will be discussed.


Characterization of Markerless Tumor Tracking Using the On-Board Imager of a Commercial Linear Accelerator Equipped With Fast-kV Switching Dual-Energy Imaging.
To describe and characterize fast-kV switching, dual-energy (DE) imaging implemented within the on-board imager of a commercial linear accelerator for markerless tumor tracking (MTT). Fast-kV switching, DE imaging provides for rapid switching between programmed tube voltages (ie, 60 and 120 kVp) from one image frame to the next. To characterize this system, the weighting factor used for logarithmic subtraction and signal difference-to-noise ratio were analyzed as a function of time and frame rate. MTT was evaluated using a thorax motion phantom and fast kV, DE imaging was compared versus single energy (SE) imaging over 360 degrees of rotation. A template-based matching algorithm was used to track target motion on both DE and SE sequences. Receiver operating characteristics were used to compare tracking results for both modalities. The weighting factor was inversely related to frame rate and stable over time. After applying the frame rate-dependent weighting factor, the signal difference-to-noise ratio was consistent across all frame rates considered for simulated tumors ranging from 5 to 25 mm in diameter. An analysis of receiver operating characteristics curves showed improved tracking with DE versus SE imaging. The area under the curve for the 10-mm target ranged from 0.821 to 0.858 for SE imaging versus 0.968 to 0.974 for DE imaging. Moreover, the residual tracking errors for the same target size ranged from 2.02 to 2.18 mm versus 0.79 to 1.07 mm for SE and DE imaging, respectively. Fast-kV switching, DE imaging was implemented on the on-board imager of a commercial linear accelerator. DE imaging resulted in improved MTT accuracy over SE imaging. Such an approach may have application for MTT of patients with lung cancer receiving stereotactic body radiation therapy, particularly for small tumors where MTT with SE imaging may fail.


Immunodetection of protein glycoforms encoded by two independent genes of the self-incompatibility multigene family of brassica.
Glycoprotein products of two highly homologous Brassica S gene family members were studied: SLSG (S locus-specific glycoprotein), product of an SLG gene at the S locus, and SLR1 (S locus-related) protein, product of the SLR1 gene, a gene unlinked to the S locus. A polyclonal antibody directed against a trpE-SLR1 fusion protein facilitated study of the SLR1 protein. SLR1 protein was detected in a number of crucifer species. No variation in the level of this protein was found between self-compatible and self-incompatible plants. Both SLSG and SLR1 protein occurred as glycoforms on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels. Each glycoform had several charge forms, indicated by elution patterns from a high performance liquid chromatography cation exchange column and behavior on two-dimensional gels. Deglycosylation of both SLSG and SLR1 protein caused loss of the glycoforms, which apparently arose from differences in glycosylation. Consistent with their apparent similar post-translational processing, immunolocalization showed that SLR1 protein, like SLSG, accumulated in the stigma papillae cell walls. Thus, both SLSG and SLR1 protein are present at the site of pollen-stigma interaction.


Family accommodation in Chinese individuals with obsessive-compulsive disorder.
Family accommodation is a common, treatment-relevant construct related to obsessive-compulsive disorder (OCD) severity and treatment outcome. This initial study examined the nature, incidence, and clinical correlates of family accommodation in Chinese adults with OCD and their relative or person in a close relationship. One hundred four outpatients diagnosed with OCD completed self-report measures of obsessive-compulsive, anxiety, and depression symptoms. Additionally, the individuals with OCD and a relative completed a measure of family accommodation and impairment. Patient-reports of family accommodation were significantly correlated with OCD symptomology and severity. A multiple linear regression indicated that OCD symptomology was a significant predictor of family accommodation, but anxiety, stress, and depression were not. In addition, the current Chinese sample demonstrated greater levels of family accommodation than previous English-speaking samples. Potential explanations and implications of the high levels of reported family accommodation are discussed. Family accommodation could play a significant role in OCD development and/or maintenance in China. Future research considerations are discussed.


The RhoA GEF Syx is a target of Rnd3 and regulated via a Raf1-like ubiquitin-related domain.
Rnd3 (RhoE) protein belongs to the unique branch of Rho family GTPases that has low intrinsic GTPase activity and consequently remains constitutively active [1], [2]. The current consensus is that Rnd1 and Rnd3 function as important antagonists of RhoA signaling primarily by activating the ubiquitous p190 RhoGAP [3], but not by inhibiting the ROCK family kinases. Rnd3 is abundant in mouse embryonic stem (mES) cells and in an unbiased two-step affinity purification screen we identified a new Rnd3 target, termed synectin-binding RhoA exchange factor (Syx), by mass spectrometry. The Syx interaction with Rnd3 does not occur through the Syx DH domain but utilizes a region similar to the classic Raf1 Ras-binding domain (RBD), and most closely related to those in RGS12 and RGS14. We show that Syx behaves as a genuine effector of Rnd3 (and perhaps Rnd1), with binding characteristics similar to p190-RhoGAP. Morpholino-oligonucleotide knockdown of Syx in zebrafish at the one cell stage resulted in embryos with shortened anterior-posterior body axis: this phenotype was effectively rescued by introducing mouse Syx1b mRNA. A Rnd3-binding defective mutant of Syx1b mutated in the RBD (E164A/R165D) was more potent in rescuing the embryonic defects than wild-type Syx1b, showing that Rnd3 negatively regulates Syx activity in vivo. This study uncovers a well defined Rnd3 effector Syx which is widely expressed and directly impacts RhoA activation. Experiments conducted in vivo indicate that Rnd3 negatively regulates Syx, and that as a RhoA-GEF it plays a key role in early embryonic cell shape changes. Thus a connection to signaling via the planar cell polarity pathway is suggested.


Red blood cell as a universal optoacoustic sensor for non-invasive temperature monitoring.
Optoacoustic (photoacoustic) temperature imaging could provide improved spatial resolution and temperature sensitivity as compared to other techniques of non-invasive thermometry used during thermal therapies for safe and efficient treatment of lesions. However, accuracy of the reported optoacoustic methods is compromised by biological variability and heterogeneous composition of tissues. We report our findings on the universal character of the normalized temperature dependent optoacoustic response (ThOR) in blood, which is invariant with respect to hematocrit at the isosbestic point of hemoglobin. The phenomenon is caused by the unique homeostatic compartmentalization of blood hemoglobin exclusively inside erythrocytes. On the contrary, the normalized ThOR in aqueous solutions of hemoglobin showed linear variation with respect to its concentration and was identical to that of blood when extrapolated to the hemoglobin concentration inside erythrocytes. To substantiate the conclusions, we analyzed optoacoustic images acquired from the samples of whole and diluted blood as well as hemoglobin solutions during gradual cooling from +37 to -15 °C. Our experimental methodology allowed direct observation and accurate measurement of the temperature of zero optoacoustic response, manifested as the sample's image faded into background and then reappeared in the reversed (negative) contrast. These findings provide a framework necessary for accurate correlation of measured normalized optoacoustic image intensity and local temperature in vascularized tissues independent of tissue composition.


Factor structures of Taiwanese teachers' ratings of ADHD: a comparison with U.S. studies.
The purpose of this study was to compare factor structures from Taiwanese teachers' ratings with diagnostic definitions of attention-deficit/hyperactivity disorder (ADHD) as described in the DSM-III-R, DSM-IV, and ICD-10; to examine how factor structures of Taiwanese teachers' ratings of ADHD symptoms compare with factor structures reported in research using school-based American participants; and to examine gender differences. One hundred and twenty-one homeroom teachers from six public elementary schools in Taipei County, Taiwan, rated two boys and two girls randomly selected from their homerooms using the ADHD checklist. Findings from this study support the concurrent validity of the DSM-IV ADHD factor structures of hyperactivity-impulsivity and inattention. Comparability of these findings with school-based U.S. studies suggests the cross-cultural congruency of behaviors associated with ADHD.


Integrated analysis of phosphoproteome and ubiquitylome in epididymal sperm of buffalo (Bubalus bubalis).
In mammals, sperm need to mature in the epididymis to gain fertilization competency. However, the molecular mechanism underlying buffalo sperm maturation remains elusive. Exploring sperm physiology at the posttranslational modification (PTM) level could help to develop our understanding of these mechanisms. Protein phosphorylation and ubiquitination are major PTMs in the regulation of many biological processes. In the present study, to our knowledge, we report the first phosphoproteome and ubiquitylome of sperm collected from the caput, corpus, and cauda segments of the epididymis using liquid chromatography-mass spectrometry combined with affinity purification. In total, 647 phosphorylation sites in 294 proteins and 1063 ubiquitination sites in 446 proteins were characterized. Some of these proteins were associated with cellular developmental processes and energy metabolic pathways. Interestingly, 84 proteins were both phosphorylated and ubiquitinated, simultaneously. Some of these proteins were involved in, for example, spermatogenesis, reproduction, and spermatid development. Taken together, these data provide a theoretical basis for further functional analysis of phosphorylation and ubiquitination in epididymal sperm of buffalo and other mammals, and serve as an important resource for exploring the physiological mechanism underlying sperm maturation.


Metabolic syndrome and outcome in patients with acute myocardial infarction.
The impact of the metabolic syndrome/insulin resistance syndrome (MS/IRS) on the severity and prognosis of acute ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) was assessed using the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) definition from 2003. A total of 385 patients having suffered acute STEMI and treated with primary PCI over a two-year period were divided into two groups (with and without MS/IRS) and compared according to the parameters of severity (clinical, laboratory, echocardiography, coronary angiography parameters and complications) and prognosis using major adverse cardiovascular events (MACE) during the six-month follow-up of acute STEMI. In comparison with control group, the MS/IRS group of patients had worse or similar results of almost all study parameters of severity (hospital days 6.5 versus 6.5, cardiogenic shock 2.9% versus 2.6%, cardiac arrest 6.8% versus 5.2%, reinfarction 0.5 versus 1.6%) and prognosis (total MACE 30.7 versus 30.7%), however, none of the differences reached statistical significance. It is concluded that the unexpected lack of such differences in MS/IRS could be due to the absence ofwaist-to-hip ratio in the definition and other open questions in metabolic syndrome in general.


Radiofrequency Thermal Lesioning and Extracorporeal Shockwave Therapy: A Comparison of Two Methods in the Treatment of Plantar Fasciitis.
We compared the results of radiofrequency thermal lesioning (RTL) and extracorporeal shockwave therapy (ESWT) in patients with chronic plantar fasciitis. This prospective study included 56 patients diagnosed with plantar fasciitis who had complaints for ≥6 months: 40 (group 1) underwent ESWT and 16 (group 2) underwent RTL. The presence of calcaneal spurs was investigated with imaging studies. All patients were followed up clinically at baseline and 1, 3, and 6 months after treatment. Clinical evaluations were performed by the visual analog scale (VAS) and the modified Roles-Maudsley (RM) scoring system. There was no significant difference in the age, sex, body mass index, and side of involvement between the groups (all P > .05). Radiographic evaluation showed calcaneal spurs in 22 patients (55%) in group 1 and 7 patients (43%) in group 2. There was no significant difference in the baseline and posttreatment values between the groups; however, group 2 had significantly different RM values at 1 month than group 1 ( P < .05). In both groups, the VAS scores significantly decreased at 1, 3, and 6 months after treatment ( P < .05). The RM scores at 1, 3, and 6 months after treatment significantly decreased in both groups, except for the RM values at 1 month after treatment in group 1 ( P < .05). Our study results suggest that RTL and ESWT are safe and effective treatments in patients with chronic plantar fasciitis. Level II: Therapeutic study.


Local and global costs of adaptive plasticity to density in Arabidopsis thaliana.
Although phenotypic plasticity is demonstrably adaptive in a range of settings, organisms are not perfectly plastic. Costs of plasticity comprise one factor predicted to counter the evolution of this adaptive strategy, yet evidence of costs is rare. Here, we test the fitness effects of plastic life-history and morphological responses to density and costs of this plasticity in recombinant inbred lines of Arabidopsis thaliana. Several costs of plasticity and homeostasis were detected. Of particular relevance, there was a significant cost of plasticity to active stem-elongation responses, an adaptive trait in many species. There was also a cost of plasticity to apical branch production at both high and low density, which resulted from the greater suppression of basal branching in genotypes with plastic apical branch production relative to genotypes with fixed apical branch production. The presence of a cost in multiple environments (i.e., a global cost) is predicted to counter the evolution of plasticity. Experimental segregating progenies such as the one used here are expected to have higher genetic costs of plasticity than arrays of genotypes sampled from natural populations because selection should remove genotypes with costs resulting from linkage disequilibrium or epistasis. The use of experimental progeny arrays therefore increases the ability to evaluate genetic costs.


Review of 'emerging' organic contaminants in biosolids and assessment of international research priorities for the agricultural use of biosolids.
A broad spectrum of organic chemicals is essential to modern society. Once discharged from industrial, domestic and urban sources into the urban wastewater collection system they may transfer to the residual solids during wastewater treatment and assessment of their significance and implications for beneficial recycling of the treated sewage sludge biosolids is required. Research on organic contaminants (OCs) in biosolids has been undertaken for over thirty years and the increasing body of evidence demonstrates that the majority of compounds studied do not place human health at risk when biosolids are recycled to farmland. However, there are 143,000 chemicals registered in the European Union for industrial use and all could be potentially found in biosolids. Therefore, a literature review of 'emerging' OCs in biosolids has been conducted for a selection of chemicals of potential concern for land application based upon human toxicity, evidence of adverse effects on the environment and endocrine disruption. To identify monitoring and research priorities the selected chemicals were ranked using an assessment matrix approach. Compounds were evaluated based upon environmental persistence, human toxicity, evidence of bioaccumulation in humans and the environment, evidence of ecotoxicity and the number and quality of studies focussed on the contaminant internationally. The identified chemicals of concern were ranked in decreasing order of priority: perfluorinated chemicals (PFOS, PFOA); polychlorinated alkanes (PCAs), polychlorinated naphthalenes (PCNs); organotins (OTs), polybrominated diphenyl ethers (PBDEs), triclosan (TCS), triclocarban (TCC); benzothiazoles; antibiotics and pharmaceuticals; synthetic musks; bisphenol A, quaternary ammonium compounds (QACs), steroids; phthalate acid esters (PAEs) and polydimethylsiloxanes (PDMSs). A number of issues were identified and recommendations for the prioritisation of further research and monitoring of 'emerging' OCs for the agricultural use of biosolids are provided. In particular, a number of 'emerging' OCs (PFOS, PFOA and PCAs) were identified for priority attention that are environmentally persistent and potentially toxic with unique chemical properties, or are present in large concentrations in sludge, that make it theoretically possible for them to enter human and ecological food-chains from biosolids-amended soil.


Outcomes of peritoneal dialysis in elderly vs non-elderly patients: A systemic review and meta-analysis.
Several studies have compared outcomes of peritoneal dialysis (PD) between elderly and non-elderly patients but with variable results. We hereby designed this review to compare mortality, peritonitis, and technique survival between elderly and non-elderly patients on PD. PubMed, Embase, and Google Scholar were searched for studies comparing outcomes of PD between elderly and non-elderly patients. The last search date was 14th July 2021. Fourteen studies were included. 12 studies defined the elderly as ≥65 years of age and these were included in the meta-analysis. Pooled analysis of crude (RR: 2.45 95% CI: 1.36, 4.40 I2 = 97% p = 0.003) and adjusted data (HR: 2.80 95% CI: 2.45, 3.09 I2 = 0% p<0.00001) indicated a statistically significant increased risk of mortality amongst elderly patients as compared to non-elderly patients. Meta-analysis of four studies demonstrated a statistically significant increased risk of peritonitis in the elderly (RR: 1.56 95% CI: 1.18, 2.07 I2 = 76% p = 0.002). Pooled analysis demonstrated no statistically significant difference in technique survival between the two groups (RR: 0.95 95% CI: 0.86, 1.05 I2 = 86% p = 0.32). Elderly patients on PD have a significantly increased risk of mortality as compared to non-elderly patients. The risk of peritonitis is also significantly increased in older adults but the increased age has no impact on technique survival. Further studies are needed to strengthen our conclusions.


Isolation and characterization of a protein from hagfish serum that is homologous to the third component of the mammalian complement system.
The 192-kDa protein HX, a major component of serum that specifically binds to zymosan particles, was prepared from the plasma of the hagfish (Eptatretus burgeri) by ion-exchange chromatography and gel filtration. HX, present at a concentration of 0.8 mg/ml in the original plasma, was composed of two distinct subunits of 115 kDa and 77 kDa, respectively, which were linked by disulfide bonds. The protein had the same electrophoretic mobility as beta-globulin. Digestion by trypsin resulted in a specific cleavage of the 115-kDa subunit and a change in its immunoelectrophoretic mobility in the anodal direction, leaving the 77-kDa subunit intact. Treatment with SDS and urea resulted in the splitting of the 115-kDa subunits into 68-kDa and 45-kDa components, but this splitting was inhibited by pretreatment with methylamine, suggesting the presence of a thiol ester bond in the 115-kDa subunit. The amino acid composition of HX revealed a striking resemblance to that of human C3. We conclude, therefore, that the 192-kDa protein isolated in this study is analogous to C3, which plays a key role in the mammalian C system.


[The present situation of home infusion therapy (HIT) and the problems of coordinated service].
Fujisawa Pharmaceutical Co., Ltd. established its home care business division in April, 1995. On the assumption that the patients have the final say in decision making, we aim at smooth operation of home care, adjusted to each patient's needs, which will lead to improvements in quality of life (QOL). Approximately 700 patients took advantage of our pharmacy service between April, 1995 and March, 1999; of them, almost 80 percent had a malignant tumor in the terminal stage and were receiving home parenteral nutrition (HPN). Patient ages ranged from the 50s to the 80s. The number of patients with a malignant disease who take advantage of medical treatment by family doctors or a visiting nurse station is less than that of patients with a benign disease. Following are the problems of coordination for HIT patients: 1) difficulty in understanding the patient's or their family's actual thoughts about home care, 2) insufficient information from the medical staff to the patient or their family for decision making, 3) insufficient coordination in the medical organization, and 4) failure of information exchange between the medical organization's staff and the home-care staff. In order to operate a home care service which can improve QOL, information exchange and cooperation among the members of the home care team is essential.


Parking Slot Detection on Around-View Images Using DCNN.
Due to the complex visual environment and incomplete display of parking slots on around-view images, vision-based parking slot detection is a major challenge. Previous studies in this field mostly use the existing models to solve the problem, the steps of which are cumbersome. In this paper, we propose a parking slot detection method that uses directional entrance line regression and classification based on a deep convolutional neural network (DCNN) to make it robust and simple. For parking slots with different shapes and observed from different angles, we represent the parking slot as a directional entrance line. Subsequently, we design a DCNN detector to simultaneously obtain the type, position, length, and direction of the entrance line. After that, the complete parking slot can be easily inferred using the detection results and prior geometric information. To verify our method, we conduct experiments on the public ps2.0 dataset and self-annotated parking slot dataset with 2,135 images. The results show that our method not only outperforms state-of-the-art competitors with a precision rate of 99.68% and a recall rate of 99.41% on the ps2.0 dataset but also performs a satisfying generalization on the self-annotated dataset. Moreover, it achieves a real-time detection speed of 13 ms per frame on Titan Xp. By converting the parking slot into a directional entrance line, the specially designed DCNN detector can quickly and effectively detect various types of parking slots.


A Retrospective Study Comparing Nose, Lip, and Chin Morphology in Class I, Class II, and Class III Skeletal Relationships in Patients Visiting to the Department of Orthodontics, BPKIHS: A Cephalometric Study.
With the changing paradigm from primarily hard tissue to soft tissue evaluation for orthodontic diagnosis and treatment planning, the priority has shifted to bring about improvement in the profile and smile characteristics of patients. Since not only the esthetics but also the stability of orthodontic treatment is largely determined by the soft tissue envelope, proper positioning of the soft tissue drape becomes paramount. Soft tissues of face, namely, nose, lips, and chin, are of paramount importance not only from an esthetic but also from functional and treatment stability points. To determine the morphological variation of lips, nose, and chin in different skeletal malocclusions. Lateral cephalograms of 237 patients visiting the department of orthodontics, BPKIHS, were taken, hand traced on matt acetate tracing paper of 0.002″ thickness with 0.3-mm 2B pencil. Samples were divided into 3 skeletal classes based on ANB angle. Measurements were made in relation to the nose, lips, and chin. Data were inserted in to SPSS and analyzed statistically using descriptive statistics, and mean and standard deviation was calculated for each variable. Multiple comparison between groups was done with post hoc Bonferroni test with mean difference significant at p < 0.05. On intergroup comparison, a significant difference was found for upper lip thickness (ULT) between Class II and Class III, and lower lip length (LLL) between Class I and Class III, and between Class II and Class III. Significant difference for nasolabial angle (NLA) was found between Class II and Class III. Similarly, a significant difference for the vertical chin parameter (CTV) was found between Class I and Class III, and between Class II and Class III. Both upper and lower lip thicknesses were highest for Class III followed by Class I and Class II, respectively. Lip lengths too were found to be highest for Class III skeletal relation. Nasolabial angle was larger in Class II malocclusion when compared to Class I and Class III. Similarly, both nasal length and nasal height measurements were in the order of Class III > Class II > Class I. Both horizontal and vertical chin parameters were larger for Class III sagittal relation.


The role of endothelin, protein kinase C and free radicals in the mechanism of the post-ischemic endothelial dysfunction in guinea-pig hearts.
Transient ischemia has been shown to impair endothelium-dependent, but not endothelium-independent, coronary vasodilation, indicating selective endothelial dysfunction. Here a hypothesis was tested that agonist mediated activation of protein kinase C (PKC) and the related overproduction of the oxidative species contribute to the mechanism of the endothelial dysfunction. Perfused guinea-pig hearts were subjected either to 30 min global ischemia/30 min reperfusion or to 30 min aerobic perfusion with a PKC activator, phorbol ester (1 n M, PMA). Coronary flow responses to a bolus of acetylcholine (ACh) and sodium nitroprusside (SNP) were used as measures of endothelium-dependent and endothelium-independent vascular function, respectively. Salicylate hydroxylation was used as the assay for the myocardial hydroxyl radical (.OH) formation. Both ischemia/reperfusion and PMA impaired the ACh response and augmented the myocardial.OH production. The effect of ischemia/reperfusion on the ACh response: (i) was fully prevented by a PKC inhibitor, chelerythrine (2microM) and a mixed endothelin blocker, bosentan (20microM); (ii) was partially prevented by an endothelin converting-enzyme inhibitor, phosphoramidon (40microM), and superoxide dismutase (150-500 U/ml, SOD) and (iii) was affected neither by catalase (600 U/ml) nor by losartan (20microM) and captopril (250microM), nor by prazosin (10microM). SOD, but not bosentan, partially prevented the effect of PMA on the ACh response. None of the interventions studied affected the SNP response. The reperfusion-induced.OH release was attenuated by chelerythrine and bosentan, was not affected by prazosin and was increased by SOD. These results implicate the following sequence of events in the mechanism of the post-ischemic endothelial dysfunction: ischemia/reperfusion, endothelin-induced PKC activation, increased production of superoxide and/or some of its toxic metabolite, damage to the endothelium and endothelial dysfunction. The results argue against the contribution of angiotensin II, adrenergicalpha(1)-receptors and kinins in the mechanism of the post-ischemic endothelial dysfunction in guinea-pig hearts.


Local Control and Toxicity of Multilevel Spine Stereotactic Body Radiotherapy.
Spine stereotactic body radiotherapy (sSBRT) is commonly limited to 1 or 2 vertebral levels given a paucity of efficacy and toxicity data when more than 2 levels are treated. To prove our hypothesis that multilevel sSBRT could provide similar rates of local control (LC) (primary endpoint) and toxicity as single-level treatment using the same clinical target, planning target, and planning organ-at-risk volumes. We analyzed consecutive cases of sSBRT treated from 2013 to 2017. Time-to-event outcomes for single-level and multilevel cases were compared using mixed effect Cox models and differences in toxicity rates were evaluated using linear mixed effect models. All models incorporate a patient-level random intercept to account for any within-patient correlation across cases. There were 101 single-level and 84 multilevel sSBRT cases (2-7 continuous vertebral levels). One-year LC was 95% vs 85%, respectively. After adjusting for baseline covariates, dose delivered, and accounting for within-patient correlation, there was no significant difference in time to local failure (hazard ratio, HR 1.79 [0.59-5.4]; P = .30). Pain improved in 83.5% of the 139 initially symptomatic tumors. There were no significant differences in grade 2+ acute or late toxicities between single-level and multilevel sSBRT. With rigorous patient immobilization, quality assurance, and image guidance, multilevel sSBRT provides high rates of LC, similar to single-level treatment, without need for larger planning volume margins. Efforts to improve prognostication and case selection for multilevel sSBRT are warranted to ensure that the benefits of improved LC over palliative radiation are justified.


Lifetime reproductive success of female mountain gorillas.
Studies of lifetime reproductive success (LRS) are important for understanding population dynamics and life history strategies, yet relatively little information is available for long-lived species. This study provides a preliminary assessment of LRS among female mountain gorillas in the Virunga volcanoes region. Adult females produced an average of 3.6 ± 2.1 surviving offspring during their lifetime, which indicates a growing population that contrasts with most other great apes. The standardized variance in LRS (variance/mean(2) = 0.34) was lower than many other mammals and birds. When we excluded the most apparent source of environmental variability (poaching), the average LRS increased to 4.3 ± 1.8 and the standardized variance dropped in half. Adult lifespan was a greater source of variance in LRS than fertility or offspring survival. Females with higher LRS had significantly longer adult lifespans and higher dominance ranks. Results for LRS were similar to another standard fitness measurement, the individually estimated finite rate of increase (λ(ind) ), but λ(ind) showed diminishing benefits for greater longevity.


Financial Hardship Among Hispanic Women with Thyroid Cancer.
Background: Little is known about financial hardship among Hispanic women with thyroid cancer. The goal of this study was to determine the prevalence of financial hardship and to identify correlates of financial hardship in this understudied patient group. Methods: We surveyed Hispanic women who had diagnoses of thyroid cancer reported to the Los Angeles Surveillance Epidemiology and End Results (SEER) registry in 2014-2015, and who had previously completed our thyroid cancer survey in 2017-2018 (N = 273; 80% response rate). Acculturation was assessed with the Short Acculturation Scale for Hispanics (SASH). Patients were asked about three outcome measures since their thyroid cancer diagnosis: (i) financial status, (ii) insurance status, and (iii) material measures of financial hardship, collapsed into a single composite measure of financial hardship. We used multivariable logistic regression to identify correlates of financial hardship. Results: Patients' median age at diagnosis was 47 years (range 20-79 years); 49% were low-acculturated and 47% reported financial hardship. Since their thyroid cancer diagnosis, 31% and 12% of the cohort reported being worse off regarding financial and insurance status, respectively. In multivariable analysis, high-acculturated older women were less likely to experience financial hardship compared with high-acculturated 20-year-old women. While financial hardship decreased with age for high-acculturated women (p = 0.002), financial hardship remained elevated across all age groups for low-acculturated women (p = 0.54). Conclusions: Our findings suggest that across all age groups, low-acculturated Hispanic women with thyroid cancer are vulnerable to financial hardship, emphasizing the need for tailored patient-focused interventions.


Molecular characterization of putative parasitism genes in the plant-parasitic nematode Meloidogyne hispanica.
Meloidogyne hispanica (Mhi) is a difficult-to-control polyphagous root-knot nematode (RKN) species of emerging importance for economically valuable crops. Nematode secretions are likely to be the first signals perceived by the plant and are thought to be involved in various aspects of the plant-nematode interaction. The aims of this work were to identify and characterize M. hispanica parasitism genes: cathepsin L cysteine protease (cpl-1), calreticulin (crt-1), β-1,4-endoglucanase-1 (eng-1) and manganese superoxide dismutase (mnsod). As there are no genomic data available for M. hispanica, primers were designed from the conserved regions of the putative parasitism genes in M. incognita and M. hapla and used to amplify the genes in M. hispanica, which led to the successful amplification of these genes in M. hispanica. Partial gene sequences were also obtained for M. arenaria, M. hapla, M. hispanica, M. incognita and M. javanica cpl-1, crt-1, eng-1 and mnsod genes, and their phylogenetic relationship analysed. In order to determine whether these genes are differentially expressed during M. hispanica development, cDNA was amplified from mRNA isolated from eggs, second-stage juveniles (J2) and females. Amplification products were observed from cDNA of all developmental stages for the Mhi-cpl-1 and Mhi-crt-1 genes. However, the gene Mhi-crt-1 exhibited intense amplification bands in females, while the Mhi-eng-1 gene was equally amplified in eggs and J2 and the Mhi-mnsod gene was only expressed in eggs. In comparison to the other RKN species, the genes Mhi-eng-1 and Mhi-mnsod showed transcription in different nematode developmental stages.


[Chronic diarrhea due to Cryptosporidium: the efficacy of spiramycin treatment].
Cryptosporidium has received increasing attention as a pathogen in normal as well as immunocompromised persons. We report a case of cryptosporidiosis occurred in a 18-months-old-girl who was treated with spiramycin for 8 days with complete resolution of diarrhea within the first days of therapy; follow-up stool examination was negative for the protozoan. The incidence of diarrhea due to Cryptosporidium seems to be higher than it was reported before: so fecal samples, when negative for other etiological agents, should be examined for Cryptosporidium oocysts. Spiramycin seems to be an effective and well-tolerated drug: treatment is recommended in children with prolonged and/or severe diarrhea when Cryptosporidium seems to be the etiological cause of the disease.


UK Food Standards Agency Workshop Consensus Report: the choice of method for measuring 25-hydroxyvitamin D to estimate vitamin D status for the UK National Diet and Nutrition Survey.
The consensus workshop, organised on behalf of the Food Standards Agency, was convened to recommend the most appropriate and secure method for measuring vitamin D status in the UK. Workshop participants (the Expert Panel) were invited on the basis of expertise in current 25-hydroxyvitamin D (25OHD) assays, or expertise in vitamin D nutrition and metabolism or detailed knowledge and experience in the National Diet and Nutrition Survey (NDNS). A decision support matrix, which set out the particular criteria by which the different options were scored and evaluated, was used to structure the discussion. The Expert Panel agreed that five methods for measuring 25OHD should be evaluated according to eleven criteria, selected on the basis of their relevance to the NDNS. All three of the evaluating subgroups of the Expert Panel produced similar total scores over the eleven criteria for the different methods; they scored LC-MS/MS and HPLC-UV similarly highly, while the scores for the immunoassay methods were lower. The Expert Panel recommended that an LC-MS/MS method should be the preferred method for the NDNS. A detailed specification for the method will be required to ensure comparability between NDNS and the National Health and Nutrition Examination Survey in the US facilitating future comparisons. The Expert Panel also recommended that the method should be carried out in a laboratory with appropriate expertise, competency and history of records of good performance. The method should be standardised against the National Institute of Standards and Technology SRM 972. If the recommended LC-MS/MS is adopted, the Expert Panel indicated that the method should be able to discriminate the C-3 epimer of 25OHD(3), especially if used to measure 25OHD in young infants in the forthcoming Diet and Nutrition Survey of Infants and Young Children, who are known to have high circulating concentrations of the C-3 epimer.


Daily dose of itraconazole 100 mg to treat allergic bronchopulmonary aspergillosis (ABPA) related eosinophilia: a case report.
Itraconazole can be used in the treatment of allergic bronchopulmonary aspergillosis (ABPA), as add-on therapy to antiasthmatic medications. Description of the case: The case of an 83-year-old male with asthma, newly diagnosed with ABPA, is presented. A daily itraconazole dose of 100 mg managed to efficiently control eosinophilia and reduce his total IgE count, while these laboratory findings relapsed three months after stopping itraconazole. When the dose was reduced to 100 mg of itraconazole every other day, it was proved insufficient to control eosinophilia. Moreover, one year later, he is being efficiently treated with 100 mg itraconazole daily. The dose of itraconazole 100 mg can effectively treat some cases of ABPA with asthma. HIPPOKRATIA 2017, 21(3): 144-146.


Mortality and morbidity of heart diseases in Hong Kong, 1971-1994.
This the second of two feature articles at the end of this issue. "In Hong Kong, heart diseases have been the second leading cause of death, after cancer, since the 1960s.... The purpose of this article is to examine the trends of mortality and morbidity of heart diseases in Hong Kong from 1971 to 1994. Age and sex differentials of deaths due to heart diseases are also analysed.... In general, the number of deaths due to heart diseases increased with age for either sex and males were more vulnerable to heart diseases than females. The age-specific death rates of either sex were quite stable over time and no increasing trend was observed. Compared with the crude death rate due to heart diseases, the standardized death rate showed a marked downward trend. These suggest that the increase in deaths due to heart diseases was mainly due to the ageing population."


Thermal Annealing-Free SnO2 for Fully Room-Temperature-Processed Perovskite Solar Cells.
The SnO2 electron transport layer (ETL) for perovskite solar cells (PSCs) has been recognized as one of the most reported protocols due to its processing convenience, high reproducibility, and excellence in device performance. To date, the thermal annealing (TA) process is still an essential step for a high-quality SnO2 ETL to reduce the surface trap density. This however could restrict its processing with high thermal energy input and set a barrier to the easiness of manufacturing such as processing under room-temperature conditions. Herein, we report a thermal annealing-free (TAF) SnO2 ETL by an alternative UV-ozone (UVO) treatment. This technique simultaneously endows the SnO2 ETL with a deeper valence band maximum (EVB) and lower defect density. Furthermore, with this SnO2 ETL, a power conversion efficiency (PCE) of 21.46 and 22.26% was achieved based on MAPbI3 and Cs0.05(FA0.85MA0.15)0.95Pb(I0.85Br0.15)3 absorbers, respectively. Importantly, a fully room-temperature-processed (RTP) PSC based on the TAF-SnO2 ETL has been demonstrated with a PCE of 20.88% on a rigid substrate and 15.92% on a flexible substrate, which are the highest values for RTP solar cells.


Approach for identification and quantification of C-terminal peptides: incorporation of isotopic arginine labeling based on oxazolone chemistry.
C-termini of proteins often play an important role in various biological processes. The determination of the protein C-terminus is crucial because it provides not only distinct functional annotation but also a way to monitor the proteolysis-modified proteins. In this study, an isotopic labeling approach based on oxazolone chemistry was developed to achieve the identification and quantification of C-termini. Aminolysis reagents such as arginine selectively react with the α-carboxyl group at the peptide C-terminus via an oxazolone-like intermediate. Side chain carboxyl groups do not participate in this reaction. When an isotopic mixture consisting of 50% arginine ((0)Arg) and 50% C6-arginine ((6)Arg) was introduced to react with C-terminus of protein and followed by proteolysis, the C-terminal peptide could be directly recognized in the mass spectrum due to its unique isotopic paired peaks, and the sequence could be interpreted in MS2. Besides, the incorporation of an additional basic amino acid in the C-terminal peptide greatly enhanced the signal intensity for C-termini detection. Moreover, the isotopic arginine labeling strategy could be applied for relative C-termini quantitation. Our method showed an excellent correlation of the measured ratios to theoretical ratios and high reproducibility within 2 orders of magnitude of the dynamic range. The correlation coefficients (R(2)) were higher than 0.99, with the coefficients of variation (CVs) ranging from 1.16 to 10.91%. Finally, the approach was used to analyze the C-termini from Thermoanaerobacter tengcongensis , which was cultured under different temperatures. As a result, 68 C-termini have been identified, and 53 of them were quantified in total using our strategy. In addition, 24 neo-C-terminal peptides have also been discovered.


Evolutionary origin, diversification and specialization of eukaryotic MutS homolog mismatch repair proteins.
Most eubacteria, and all eukaryotes examined thus far, encode homologs of the DNA mismatch repair protein MutS. Although eubacteria encode only one or two MutS-like proteins, eukaryotes encode at least six distinct MutS homolog (MSH) proteins, corresponding to conserved (orthologous) gene families. This suggests evolution of individual gene family lines of descent by several duplication/specialization events. Using quantitative phylogenetic analyses (RASA, or relative apparent synapomorphy analysis), we demonstrate that comparison of complete MutS protein sequences, rather than highly conserved C-terminal domains only, maximizes information about evolutionary relationships. We identify a novel, highly conserved middle domain, as well as clearly delineate an N-terminal domain, previously implicated in mismatch recognition, that shows family-specific patterns of aromatic and charged amino acids. Our final analysis, in contrast to previous analyses of MutS-like sequences, yields a stable phylogenetic tree consistent with the known biochemical functions of MutS/MSH proteins, that now assigns all known eukaryotic MSH proteins to a monophyletic group, whose branches correspond to the respective specialized gene families. The rooted phylogenetic tree suggests their derivation from a mitochondrial MSH1-like protein, itself the descendent of the MutS of a symbiont in a primitive eukaryotic precursor.


The relative prevalence of disease symptoms for ill persons: evidence from Benin.
In developing countries, the usual modelling of the correlates of health problems is not a good fit for the health phenomena encountered and the available data. Indeed, three common situations occur: (a) it is often the observed symptoms that are used to determine medical interventions instead of specific disease diagnostics or general health indicators; (b) the ill persons described by the data are often affected by multiple health problems; and (c) the correlates of the full spectrum of all symptoms need to be considered together. In this paper, these issues are dealt with by proposing a statistical approach based on competing scores of symptoms that explain their relative prevalence among the observed ill persons. Using multinomial logit models, the relative prevalence of four symptoms was estimated for four age classes of ill persons in Benin. Socio-demographic characteristics, household equipment and consumption behaviour are shown to influence the relative prevalence of symptoms and therefore could be used to decide what treatment to use. Moreover, living standards and economic activities are important and the pattern of symptoms among poor or agricultural ill persons differs from that of the rich or the non-peasants. The proposed method can be used to assist the definition of target groups and to guide the allocation of scarce resources in poor countries.


Viral tracing identifies parallel disynaptic pathways to the hippocampus.
Electrophysiological and lesion studies in rodents have shown that the dorsal (septal) and ventral (temporal) segments of the hippocampus have functional specializations that can be understood in terms of their anatomical connections with distinct brain areas. Here we explore the circuitry associated with the hippocampus using the pseudorabies virus-Bartha strain (PRV-Bartha) tracer in the rat to examine both direct (first-order) and indirect (second-order) projections to the hippocampus. Based on analysis of PRV-Bartha infection density, we demonstrate two parallel pathways from the limbic cortex to the hippocampus. A dorsal "spatial cognition" pathway provides disynaptic input from the retrosplenial, anterior cingulate, and orbital cortex to the dorsal hippocampus, with potential synaptic relays in the anterior thalamic nuclei and dorsolateral entorhinal cortex. A ventral "executive control" pathway provides disynaptic input from the prelimbic, infralimbic, and orbital cortex to the ventral hippocampus, with potential synaptic relays in the midline thalamic nuclei and the rostral caudomedial entorhinal cortex. These data suggest a new anatomical framework for understanding the functional interactions between the cortex and hippocampus, especially in cognitive disorders that involve both structures, such as frontotemporal dementia.


Antibody-Coated Wearable Organic Electrochemical Transistors for Cortisol Detection in Human Sweat.
The dysregulation of the hormone cortisol is related to several pathological states, and its monitoring could help prevent severe stress, fatigue, and mental diseases. While wearable antibody-based biosensors could allow real-time and simple monitoring of antigens, an accurate and low-cost antibody-based cortisol detection through electrochemical methods is considerably challenging due to its low concentration and the high ionic strength of real biofluids. Here, a label-free and fast sensor for cortisol detection is proposed based on antibody-coated organic electrochemical transistors. The developed devices show unprecedented high sensitivities of 50 μA/dec for cortisol sensing in high-ionic-strength solutions with effective cortisol detection demonstrated with real human sweat. The sensing mechanism is analyzed through impedance spectroscopy and confirmed with electrical models. Compared to existing methods requiring bulky and expensive laboratory equipment, these wearable devices enable point-of-care cortisol detection in 5 min with direct sweat collection for personalized well-being monitoring.


Diarrhea acquired in the hospital.
Nosocomial diarrhea may be the second or third most common nosocomial infection, depending on the type of institution and the presence of outbreaks. Age is a major determinant of the type of cause of the diarrhea and, as a consequence, the choice of treatment. Control of nosocomial outbreaks is usually linked to prompt diagnosis and treatment of individual cases, interruption of the route(s) of transmission, and an increase in the awareness of infection-control procedures. Unfortunately, the complete elimination of nosocomial diarrhea is not feasible, and these infections will remain a challenge to us all in the future.


An SDN Focused Approach for Energy Aware Traffic Engineering in Data Centers.
There is a lot of effort to limit the impact of CO2 emissions from the information communication technologies (ICT) industry by reducing the energy consumption on all aspects of networking technologies. In a service provider network, data centers (DCs) are the major power consumer and considerable gains are expected by regulating the operation network devices. In this context, we developed a mixed integer programming (MIP) algorithm to optimize the power consumption of network devices via energy aware traffic engineering. We verified our approach by simulating DC network topologies and demonstrated that clear benefits can be achieved for various network sizes and traffic volumes. Our algorithm can be easily implemented as an application in the software-defined networking (SDN) paradigm, making quite feasible its deployment in a production environment.


Lenalidomide, melphalan, and prednisone association is an effective salvage therapy in relapsed plasma cell leukaemia.
Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, characterized by the presence of a peripheral blood absolute plasma cell count of at least 2 x 109/l and more than 20% circulating plasma cells. The prognosis of PCL patients remains poor. Even by using autologous or allogenic transplant procedures, median survival does not exceed 3 years (Saccaro et al., 2005). Thalidomide, bortezomib and lenalidomide (Revlimid) have emerged as high active agents in the treatment of PCL (Johnston and abdalla, 2002; Musto et al., 2007; Finnegan et al., 2006). In particular, Lenalidomide is a structural analogue of thalidomide with similar but more potent biological activity; it is used as first line therapy in MM (Palumbo et al., 2007; Niesvizky et al., 2007), although information regarding its associated use with dexamethasone use as salvage therapy in PCL derives from anecdotal single case reports (Musto et al., 2008). We would like to describe a case of primary PCL with adverse cytogenetic in which excellent response was achieved with the combination of lenalidomide, melphalan, and prednisone as salvage therapy.


Association of hyperglycaemia with the placenta of GDM-induced macrosomia with normal pre-pregnancy BMI and the proliferation of trophoblast cells.
The aim of this study was to identify the effect of hyperglycaemia on placentas of gestational diabetes mellitus (GDM) women with macrosomia and normal pre-pregnancy body mass index (BMI), and uncover the molecular mechanism of hyperglycaemia on trophoblast cells in vitro. GDM women with normal pre-pregnancy BMI were divided into GM group (macrosomia, n = 30) and GN group (normal birth weight, n = 35). The study showed GM group had more adverse pregnancy outcomes and higher levels of gestational weight gain, blood glucose and triglyceride. After adjustment for confounding factors, just the fasting plasma glucose level and HbA1c percentage were related to the incidence of GDM-induced macrosomia with normal pre-pregnancy BMI. Meanwhile, the fasting blood glucose was closely related to the placental weight and placental PCNA expression. Furthermore, the in vitro model for placenta showed that hyperglycaemia significantly promoted trophoblast cell proliferation and activated ERK1/2 phosphorylation. ERK1/2 inhibitor markedly suppressed hyperglycaemia-induced trophoblastic proliferation. The fasting plasma glucose and placenta are closely related with the development of GDM-induced macrosomia with normal pre-pregnancy BMI. The mechanism may be hyperglycaemia promotes trophoblast cell proliferation via ERK1/2 signalling. It provides scientific evidence for optimising outcomes of GDM women with normal pre-pregnancy BMI.IMPACT STATEMENTWhat is already known on this subject? Gestational diabetes mellitus (GDM) is one of the strongest risk factors correlated with macrosomia. The hyperglycaemic intrauterine environment affects not only the foetus but also the placental development and function in humans and experimental rodents. However, placental abnormalities associated with maternal diabetes have been inconsistently reported, possibly because of population differences in pre-pregnancy weight, diabetes types, glycemic control or pregnancy complication, and the molecular mechanism of hyperglycaemia on trophoblast cells in vitro was not clearly stated.What do the results of this study add? This is the first study to identify the effect of hyperglycaemia on placentas of gestational diabetes mellitus (GDM) women with macrosomia and normal pre-pregnancy body mass index (BMI), and uncover the molecular mechanism of hyperglycaemia on trophoblast cells in vitro.What are the implications of these findings for clinical practice and/or further research? Understanding placental changes in the environment of abnormal glucose metabolism which can establish the maternal-placental-foetal interface dysfunction as a potential source of adverse pregnancy outcomes is very necessary. Our study found the fasting plasma glucose and placenta are closely related with the development of GDM-induced macrosomia with normal pre-pregnancy BMI. The mechanism may be hyperglycaemia promotes trophoblast cell proliferation via ERK1/2 signalling. It provides scientific evidence for optimising outcomes of GDM women with normal pre-pregnancy BMI, and could be used for the following studies of relationship between placenta and childhood complications.


Berbamine Analogs Exhibit Differential Protective Effects From Aminoglycoside-Induced Hair Cell Death.
Hearing loss is the third most common chronic health condition in the United States and largely results from damage to sensory hair cells. Major causes of hair cell damage include aging, noise exposure, and medications such as aminoglycoside antibiotics. Due to their potent antibacterial properties and low cost, aminoglycosides are often used for the treatment of gram-negative bacterial infections, surpassing expensive antibiotics with fewer harmful side effects. However, their use is coupled with permanent hearing loss in over 20% of patients requiring these life-sustaining antibiotics. There are currently no FDA-approved drugs that prevent hearing loss from aminoglycosides. A previous study by our group identified the plant alkaloid berbamine as a strong protectant of zebrafish lateral line hair cells from aminoglycoside damage. This effect is likely due to a block of the mechanotransduction channel, thereby reducing aminoglycoside entry into hair cells. The present study builds on this previous work, investigating 16 synthetic berbamine analogs to determine the core structure underlying their protective mechanisms. We demonstrate that nearly all of these berbamine analogs robustly protect lateral line hair cells from ototoxic damage, with ED50 values nearing 20 nM for the most potent analogs. Of the 16 analogs tested, nine strongly protected hair cells from both neomycin and gentamicin damage, while one conferred strong protection only from gentamicin. These data are consistent with prior research demonstrating that different aminoglycosides activate somewhat distinct mechanisms of damage. Regardless of the mechanism, protection required the entire berbamine scaffold. Phenolic alkylation or acylation with lipophilic groups appeared to improve protection compared to berbamine, implying that these structures may be responsible for mitigating damage. While the majority of analogs confer protection by blocking aminoglycoside uptake, 18% of our analogs also confer protection via an uptake-independent mechanism; these analogs exhibited protection when delivered after aminoglycoside removal. Based on our studies, berbamine analogs represent a promising tool to further understand the pathology of aminoglycoside-induced hearing loss and can serve as lead compounds to develop otoprotective drugs.


Tissue-specific differential repression of gene expression by a dominant negative mutant of thyroid hormone beta1 receptor.
Resistance to thyroid hormone (RTH) is a genetic disease caused by the mutations of the thyroid hormone beta receptor (TRbeta) gene, producing receptors with a dominant negative action. The present study addressed the question as to whether tissue-specific factors modulate the dominant negative function in different tissues. We prepared stably transfected pituitary GH3 (GH3-PV) and liver SK-Hep-1 (SK-Hep-1-PV) cell lines with a potent dominant negative mutant, PV. The growth hormone (GH) and the malic enzyme genes (ME) in GH3 and SK-Hep-1, respectively, are directly regulated by the thyroid hormone, 3,3,'5-triiodo-L-thyronine (T3). The ratio of the expressed PV/endogenous TRbeta1 proteins was approximately 20 and 5 for GH3-PV and SK-Hep-1-PV cells, respectively. However, the T3-activated expression of the GH gene in GH3-PV and ME gene in SK-Hep-1-PV was repressed by approximately 30% and 90%, respectively, indicating the lack of correlation of PV/TRpbeta1 protein ratio with the dominant negative potency of mutant PV. Furthermore, the synergistic effect of the pituitary-specific factor 1 on the TR-mediated GH promoter activity was not repressed by mutant PV. Taken together, these results suggest that the dominant negative effect of mutant TR is variable in the tissues studied.


Synthesis and Properties of Gelatin Methacryloyl (GelMA) Hydrogels and Their Recent Applications in Load-Bearing Tissue.
Photocrosslinked gelatin methacryloyl (GelMA) hydrogels have attracted great concern in the biomedical field because of their good biocompatibility and tunable physicochemical properties. Herein, different approaches to synthesize GelMA were introduced, especially, the typical method using UV light to crosslink the gelatin-methacrylic anhydride (MA) precursor was introduced in detail. In addition, the traditional and cutting-edge technologies to characterize the properties of GelMA hydrogels and GelMA prepolymer were also overviewed and compared. Furthermore, the applications of GelMA hydrogels in cell culture and tissue engineering especially in the load-bearing tissue (bone and cartilage) were summarized, followed by concluding remarks.


Sole stenting of large and giant intracranial aneurysms with self-expanding intracranial stents-limits and complications.
Intracranial aneurysms may be difficult for endovascular treatment due to size, fusiform shape, or wide neck. In such patients, intracranial stents are used to support the coils in the aneurysm sac, or they may be used as a sole stenting technique to divert the blood flow without coils. The aim of this paper is to contribute to the existing data by reviewing the risks of sole stenting of large and giant aneurysms. We treated seven patients with nine aneurysms by self-expanding intracranial stents, either by a single or multiple stents in a stent-in-stent configuration. The follow-up was performed by digital subtraction angiography with a mean follow-up time of 6 months. A positive response to stenting occurred in five out of seven patients (71%) and six out of nine aneurysms (67%). The aneurysms were occluded in two patients, and incomplete results were noted in three patients. The symptoms due to the compression of cranial nerves resolved in four patients (57%). Procedure-related subarachnoid hemorrhage occurred in two out of seven patients (29%), with death of one patient as a result of hemorrhage (14%). Sole stenting of large and giant aneurysms with self-expanding intracranial stents may be associated with a higher risk than previously reported. The effect of stenting on intra-aneurysmal flow in such aneurysms, even after the placement of multiple overlapping stents, seems to be unpredictable.


The role of IL-4 in proliferation and differentiation of human natural killer cells. Study of an IL-4-dependent versus an IL-2-dependent natural killer cell clone.
The role of IL-4 in proliferation and differentiation of human NK cells was studied using newly established sublines of an IL-4-dependent NK cell clone (IL4d-NK cells) and an IL-2-dependent NK cell clone (IL2d-NK cells) derived from a parental conditioned medium-dependent NK cell clone (CM-NK cells). IL-4 induced the higher proliferation of CM-NK cells, but abolished their NK activity and decreased CD16 and CD56 Ag expression. In contrast, IL-2 induced the higher NK activity and increased CD16 and CD56 Ag expression. Addition of anti-IL-4 antibody to the culture of CM-NK cells with CM inhibited the proliferation, but slightly increased NK activity, and largely increased CD56 Ag expression. Addition of anti-IL-2 antibody to the culture of CM-NK cells with CM inhibited both proliferation and cytotoxicity. Proliferation of IL4d-NK cells, which is totally dependent on rIL-4, is greater than that of IL2d-NK cells, which was greater than parental CM-NK cells. Morphologically, IL4d-NK cells are small and round, whereas IL2d-NK cells are large and elongated. Anti-IL-4 antibody inhibited proliferation of IL4d-NK but not IL2d-NK cells, whereas anti-IL-2 antibody inhibited that of IL2d-NK but not IL4d-NK cells. IL-2 was not detected in the supernatant from IL4d-NK cells, nor was IL-2-mRNA expressed in IL4d-NK cells. In contrast, IFN-gamma production and protein expression in IL4d- and IL2d-NK cells were detected. NK cell activation markers (CD16 and CD56) were expressed on IL2d-NK cells but not IL4d-NK cells. IL4d-NK cells were not cytotoxic to any tumor cells tested, whereas IL2d-NK cells displayed potent NK activity and lymphokine-activated killer activity. IL4d-NK cells failed to bind K562 tumor cells, whereas one-third of the IL2d-NK cells did. IL4d-NK cells responded to rIL-2, proliferated, and differentiated into cytotoxic NK cells, whereas IL2d-NK cells failed to respond to rIL-4 and died. These results raise a possibility that IL4d-NK cells or IL2d-NK cells primarily represent the immunologic properties of immature or activated types of human NK cells, respectively. Our results provide the first evidence of the capability of IL-4 to support continuous proliferation of a lymphocyte clone with immature NK cell characteristics and to stimulate IFN-gamma production in the clone. IL-4 is suggested as a potential growth factor for certain types of human NK cell progenitors.


Metallothionein expression and transient resistance to electrophilic antineoplastic drugs.
Intrinsic and acquired resistance to antineoplastic agents remains an important impediment to cancer therapy. Intracellular metallothioneins appear to be one factor in determining the responsiveness of malignant and normal cells to electrophilic anticancer agents. Metallothioneins are not only constitutively expressed but their expression can be transcriptionally activated by a host of endogenous and exogenous substances; this is a reversible phenomenon. This inducibility affords the possibility that cells can respond quickly to toxic substances and that under certain conditions transient drug resistance may occur. We review the evidence implicating metallothioneins in anticancer drug resistance and discuss this in the context of the possibility of transient resistance.


Interactions between recovery in aphasia, emotional and psychosocial factors in subjects with aphasia, their significant others and speech pathologists.
Associations between clinical and functional aphasia recovery and perceptions of emotional and psychosocial adjustment accompanying aphasia were examined in five subjects at 3 and 9 months post-onset of stroke using a range of objective and subjective measures. The subjective well-being and optimism of significant others of aphasic patients was also examined, and speech pathologists completed measures of optimism. Unique patterns of individual emotional and psychosocial adjustment were found over time in patients and their significant others, even in patients with similar aphasia type and severity. Individual variability in emotional and psychosocial adjustment and their impact on recovery from aphasia are discussed.


Relationship between gestational diabetes mellitus and low maternal birth weight.
To study the relationship between low birth weight and the presence of gestational diabetes mellitus (GDM) or peripheral insulin resistance during pregnancy. We studied the relationship between peripheral insulin sensitivity (calculated by Matsuda and DeFronzo's oral glucose tolerance test (OGTT)-derived insulin sensitivity index [ISI(OGTT)]) or GDM prevalence and birth weight in 604 pregnant women, classified as normally glucose tolerant (n = 462) or affected with GDM (n = 142) after a 100-g 3-h oral glucose tolerance test. We then categorized these subjects into two groups: individuals with birth weight in the <10th percentile (<2,600 g; n = 68) and individuals with birth weight in the >10th percentile (n = 536). GDM prevalence was higher in the group in the lowest birth weight decile (<2,600 g; 24/68; 35%) than in the group with normal/high birth weight (118/536; 22%; chi(2) = 5.917; P = 0.01). Relative risk for GDM adjusted for age, parity, family history of diabetes, and prepregnancy body weight was about twofold in the group with low birth weight (odds ratio = 1.89 [95% CI 1.088-3.285; P = 0.023]), and the prevalence of low birth weight was about threefold higher in the first ISI(OGTT) decile. In 450 women whose newborn's weight was known, the delivery of macrosomic babies was associated with a twofold higher relative risk for GDM in women who themselves had low birth weight. In the latter, the relationships between their newborn's weight and either maternal glucose tolerance (positive) or ISI(OGTT) (negative) were amplified. Low maternal birth weight was associated with a twofold higher risk for GDM, independent of major confounders. Such a risk was highest in women with low birth weight who delivered macrosomic babies, and in the group with low birth weight, the relationship between maternal glucose tolerance or insulin resistance and offspring's neonatal weight was much more evident.


Enhancing dendritic cell-based vaccination for highly aggressive glioblastoma.
Patients with primary glioblastoma (GBM) have a dismal prognosis despite standard therapy, which can induce potentially deleterious side effects. Arming the immune system is an alternative therapeutic approach, as its cellular effectors and inherent capacity for memory can be utilized to specifically target invasive tumor cells, while sparing collateral damage to otherwise healthy brain parenchyma. Active immunotherapy is aimed at eliciting a specific immune response against tumor antigens. Dendritic cells (DCs) are one of the most potent activators of de novo and recall immune responses and are thus a vehicle for successful immunotherapy. Currently, investigators are optimizing DC vaccines by enhancing maturation status and migratory potential to induce more potent antitumor responses. An update on the most recent DC immunotherapy trials is provided. Targeting of unique antigens restricted to the tumor itself is the most important parameter in advancing DC vaccines. In order to overcome intrinsic mechanisms of immune evasion observed in GBM, the future of DC-based therapy lies in a multi-antigenic vaccine approach. Successful targeting of multiple antigens will require a comprehensive understanding of all immunologically relevant oncological epitopes present in each tumor, thereby permitting a rational vaccine design.


The potato leafroll luteovirus 17K protein is a single-stranded nucleic acid-binding protein.
The potato leafroll luteovirus protein of Mr 17K (pr17), which is encoded by an open reading frame on the 3' half of the viral genome, was expressed by using bacterial expression vector systems. Fusion proteins were obtained for the full-length viral protein as well as its N-terminal acidic (GST/pr17N) and C-proximal (GST/pr17C) basic domains and used in nucleic acid-binding studies. Filter-bound as well as soluble pr17 bound to single-stranded RNA or DNA. The binding domain was shown to reside in the basic C-proximal part of the polypeptide, whereas the N-terminal acidic domain did not show any affinity for nucleic acid. These biochemical properties of pr17 together with its structural features suggest a regulatory role for this protein during virus replication.


Optimal postoperative surveillance strategies for cancer survivors with gastric neuroendocrine carcinoma based on individual risk: a multicenter real-world cohort study.
The best follow-up strategy for cancer survivors after treatment should balance the effectiveness and cost of disease detection while detecting recurrence as early as possible. Due to the low incidence of gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma [G-(MA)NEC], high-level evidence-based follow-up strategies is limited. Currently, there is a lack of consensus among clinical practice guidelines regarding the appropriate follow-up strategies for patients with resectable G-(MA)NEC. The study included patients diagnosed with G-(MA)NEC from 21 centers in China. The random forest survival model simulated the monthly probability of recurrence to establish an optimal surveillance schedule maximizing the power of detecting recurrence at each follow-up. The power and cost-effectiveness were compared with the National Comprehensive Cancer Network, European Neuroendocrine Tumor Society, and European Society for Medical Oncology Guidelines. A total of 801 patients with G-(MA)NEC were included. The patients were stratified into four distinct risk groups utilizing the modified TNM staging system. The study cohort comprised 106 (13.2%), 120 (15.0%), 379 (47.3%), and 196 cases (24.5%) for modified groups IIA, IIB, IIIA, and IIIB, respectively. Based on the monthly probability of disease recurrence, the authors established four distinct follow-up strategies for each risk group. The total number of follow-ups 5 years after surgery in the four groups was 12, 12, 13, and 13 times, respectively. The risk-based follow-up strategies demonstrated improved detection efficiency compared to existing clinical guidelines. Further Markov decision-analytic models verified that the risk-based follow-up strategies were better and more cost-effective than the control strategy recommended by the guidelines. This study developed four different monitoring strategies based on individualized risks for patients with G-(MA)NEC, which may improve the detection power at each visit and were more economical, effective. Even though our results are limited by the biases related to the retrospective study design, we believe that, in the absence of a randomized clinical trial, our findings should be considered when recommending follow-up strategies for G-(MA)NEC.


Thermal map assessment under climate and land use changes; a case study for Uzundere Basin.
Satellite images are commonly used for defining thermal urban environment and heat islands in urban areas. The objective of this study was to analyze and evaluate thermal environment of Uzundere-Erzurum using satellite images provided by the Landsat Thematic Mapper (TM) sensor on board Landsat 5 satellite. In respect to land use and urban surface features, spatial characterization of thermal urban environment was defined. In order to define the link between surface emissivity, land surface temperatures (LST), and urban surface characteristics more effectively, the CORINE Land Cover (CLC) database for Uzundere was also used. Based on the Landsat satellite images, different land cover categories are defined, and the alterations of heat islands are identified according to these categories. The minimum and maximum surface temperatures were obtained from open spaces, non-vegetated bare rocky areas (- 1.8 and 29.1 °C, respectively). The surface temperature in the water areas was much better (7.5 and 21.9 °C) and followed by green areas surface temperature (- 0.9 and 28 °C). Surface temperatures should be considered energy-focused planning.


Photoinduced electron transfer in 2-tert-butyl-3-(anthracen-9-yl)-2,3-diazabicyclo[2.2.2]octane.
Intramolecular photoinduced electron transfer from a hydrazine unit to an aromatic group is studied by resonance Raman spectroscopy and electronic absorption spectroscopy. Substituted hydrazine functional groups have played an important role in studies of electron-transfer reactions, photoinduced intramolecular electron transfer, and of mixed valence. A prototypical compound, 2-tert-butyl-3-(anthracen-9-yl)-2,3-diazabicyclo[2.2.2]octane, that has the hydrazine-to-anthracene charge-transfer band in a region of the visible spectrum suitable for detailed resonance Raman spectroscopy is studied in detail. Excitation profiles are obtained, calculated quantitatively by using time-dependent theoretical methods, and interpreted with the assistance of molecular orbital calculations. Excited-state distortions are calculated. The largest distortions occur on the hydrazine unit; the normal mode showing the largest distortion (659 cm(-1), calculated at 665 cm(-1)) involves an out-of-plane C-N-N-C bend consistent with removing an electron from the N-N pi antibonding orbital. Anthracene ring-centered C-C stretches also are enhanced, consistent with populating an antibonding pi orbital centered on the ring. Excellent fits to all of the excitation profiles and to the absorption band are obtained using one set of excited-state potential surfaces.


Synthesis of highly fluorinated 2,2'-biphenols and 2,2'-bisanisoles.
Multiply fluorine-substituted iodo anisoles are efficiently coupled in an Ullmann-type reaction to provide the corresponding bisanisoles. The coupling is selective and even tolerates bromo moieties. Subsequent deprotection of hydroxy groups gives access to highly fluorinated biphenols.


Sphingosine-1-phosphate and its receptors in anti-neutrophil cytoplasmic antibody-associated vasculitis.
C5a plays a crucial role in anti-neutrophil cytoplasmic antibody (ANCA)-mediated neutrophil recruitment and activation. Our previous studies found that the interaction between sphingosine-1-phosphate (S1P) and C5a plays an important role in the ANCA-mediated activation of neutrophils. In the current study, the expression levels of S1P in plasma and its receptors (S1PR1-5) in kidneys were analysed in patients with ANCA-associated vasculitis (AAV). Plasma samples from 32 AAV patients in active stage and 20 AAV patients in remission were collected. The plasma levels of S1P were determined by an enzyme-linked immunosorbent assay (ELISA). The expression of S1PR1-5 in the renal specimens from 24 AAV patients was detected by immunohistochemistry. The associations of the plasma levels of S1P and renal expression of S1PRs with clinical and pathological parameters were analysed. The level of plasma S1P was significantly higher in AAV patients in active stage than it was in both patients in remission and in normal controls. Correlation analysis showed that the plasma levels of S1P correlated with the initial serum creatinine levels (r = 0.502, P = 0.003) and inversely correlated with the estimated glomerular filtration rate (eGFR; r = -0.358, P = 0.044) in AAV patients. Double-labelling immunofluorescence assay suggested that S1PR1-5 were expressed on endothelial cells in the glomeruli and that S1PR1, 4 and 5 were expressed on neutrophils. In AAV patients, the circulating S1P levels were elevated and the renal expression of S1PR2-5 was upregulated. The levels of circulating S1P and the renal expression of S1PR were associated with the renal involvement and disease activity of AAV.


[Anaphylactic shock revealing anisakiasis].
The manifestations of anisakiasis are essentially digestive pain, nausea or transit disorders. When it is initially asymptomatic, it is later revealed by a major complication, which is occlusion on an eosinophilic granuloma of the ileum. Over the past 5 years, the international literature has reported allergic manifestations related to this helminthozoonose, such as urticaria, angioedema, bronchospasm and occasionally anaphylactic shock. A 60 year-old man presented with an anaphylactic shock and diarrhea. One month later, he exhibited persisting asthenia, cough and intermittant pruriginous rashes. Blood hypereosinophilia was borderline and total IgE was clearly increased. The initial event was retrospectively labeled "histaminic shock following ingestion of tuna fish". The discovery of highly positive anisakiasis serology, conducted simultaneously in 2 different laboratories, corrected the diagnosis. The patient was treated with albendazole (10 mg/kg/day for 7 days) with excellent results on the clinical and biological symptomatology. With the occurrence of an allergic reaction, whether major or minor, a notion of ingestion of fresh fish must be searched for and, if positive, an immunodiagnosis of anisakiasis must be requested. Any seriological positivity should be controled by gastro-duodenal endoscopy. If the search for larvae is negative, we recommend anthelminthic treatment as a precaution.


Mixtures of tense and relaxed state polymerized human hemoglobin regulate oxygen affinity and tissue construct oxygenation.
Pure tense (T) and relaxed (R) quaternary state polymerized human hemoglobins (PolyhHbs) were synthesized and their biophysical properties characterized, along with mixtures of T- and R-state PolyhHbs. It was observed that the oxygen affinity of PolyhHb mixtures varied linearly with T-state mole fraction. Computational analysis of PolyhHb facilitated oxygenation of a single fiber in a hepatic hollow fiber (HF) bioreactor was performed to evaluate the oxygenation potential of T- and R-state PolyhHb mixtures. PolyhHb mixtures with T-state mole fractions greater than 50% resulted in hypoxic and hyperoxic zones occupying less than 5% of the total extra capillary space (ECS). Under these conditions, the ratio of the pericentral volume to the perivenous volume in the ECS doubled as the T-state mole fraction increased from 50 to 100%. These results show the effect of varying the T/R-state PolyhHb mole fraction on oxygenation of tissue-engineered constructs and their potential to oxygenate tissues.


[Churg-Strauss syndrome].
Churg-Strauss syndrome is a systemic and pulmonary vasculitis, defined by its association with severe asthma and with hypereosinophilia of the blood and tissues. The systemic vasculitis is a small-vessel vasculitis frequently associated with purpura, mononeuritis multiplex, and, more rarely, with rapidly progressive glomerulonephritis or diffuse alveolar hemorrhage. Its prevalence of 7 to 13 per million population makes it one of the rarest of the systemic vasculitides. Anti-MPO (antimyeloperoxydase) pANCA (ANCA with a perinuclear fluorescence pattern) are present in 35-40% of cases and appear to determine a subgroup of patients with a higher frequency of renal damage, alveolar hemorrhage, and central nervous system involvement. The diagnosis of Churg-Strauss syndrome is made on the basis of clinical features. In patients with late onset asthma the presence of constitutional symptoms, eosinophilia (> 1000/mm3), the appearance of a systemic illness characterized by monoreutis multiplex, purpura, cardiomyopathy or pulmonary infiltrates should lead to consider the diagnosis of Churg-Strauss syndrome. Cardiac involvement is an important cause of morbidity and the leading cause of specific mortality in Churg-Strauss syndrome. Treatment is based on corticosteroid therapy and immunosuppressive drugs (cyclophosphamide and azathioprine) and is determined according to validated prognostic criteria (Five Factors Score). Complete remission occurs in almost 90% of cases, and the 10-year survival rate has reached 79.4%. Relapses are frequent (25% of cases) and even after recovery from vasculitis, most patients (90%) still have asthma requiring corticosteroid treatment.


Impact of mycolic acid deficiency on cells of Corynebacterium glutamicum ATCC13869.
Mycolic acid (MA) plays important role in Corynebacterium glutamicum, but the key enzymes in the biosynthetic pathway of MA in C. glutamicum ATCC13869 have not been characterized. Since the locus BBD29_RS14045 in C. glutamicum ATCC13869 shows high similarity to the gene Cgl2871, which encodes Pks13, the key enzyme for synthesizing MA in C. glutamicum ATCC13032, it was deleted, resulting in the mutant WG001. Compared with the wild-type ATCC13869, MA was not synthesized in WG001, but more phosphatidylglycerol and phosphatidylinositol containing longer unsaturated fatty acids were produced. WG001 cells also show hindered cell growth and defective cell separation when compared with ATCC13869 cells. Transcriptomic analysis shows that many genes relevant to the pathways of fatty acids, inositol, phospholipids, cell wall, and cell division were significantly regulated in WG001 cells when compared with ATCC13869 cells. This study demonstrates that the locus BBD29_RS14045 encodes a key enzyme that plays important role for synthesizing MA in C. glutamicum ATCC13869.


T suppressor hybridomas and interleukin-2-dependent lines induced by copolymer 1 or by spinal cord homogenate down-regulate experimental allergic encephalomyelitis.
Suppressor T (Ts) hybridomas and interleukin-2-dependent T cell lines were established from spleens of mice, which had been rendered unresponsive to experimental allergic encephalomyelitis (EAE) either by mouse spinal cord homogenate or by the synthetic suppressant copolymer 1 (Cop 1). The Ts hybridoma supernatants and the Ts line cells specifically suppressed the in vitro response to the encephalitogenic myelin basic protein (BP), as indicated by inhibition of both the proliferation and interleukin-2-secretion responses of a BP-specific T cell line. Moreover, these Ts cells prevented the development of actively induced EAE in vivo. All hybridomas and lines were most effective when injected at the time of disease induction, thus suggesting that they operate as effector suppressor cells, and functionally inhibit encephalitogenic responses. The data presented here suggest that the suppressor cells are stimulated by the protective epitopes included in the BP as well as in the Cop 1 molecules and that they play an active role in the regulation of EAE. The generation of Ts lines and hybridomas, which have been induced by Cop 1, establish the specific stimulation of suppressor cells to EAE as a mechanism underlying the therapeutic activity of Cop 1.


Transfer of contaminants in adeno-associated virus vector stocks can mimic transduction and lead to artifactual results.
The potential of adeno-associated virus (AAV) vectors for gene transfer and gene therapy applications is currently being intensively investigated. Although much progress has been made in defining AAV vector biology, inconsistencies remain in the literature regarding the efficiency of AAV transduction in various cell types. In the course of exploring these differences, we have identified a problem associated with the use of AAV vector stocks that results in overestimation of gene transfer efficiencies. We show here that biologically active vector-encoded proteins can contaminate AAV vector stocks, especially cell lysate preparations that have not been further purified, and can be transferred in a virion-independent manner to target cells, a phenomenon called pseudotransduction. This observation is significant because impure cell lysate stocks have been widely employed in the AAV literature, and we demonstrate here that this phenomenon can occur with commonly used reporter proteins such as beta-galactosidase and alkaline phosphatase. We conclude that although there are many potential explanations for apparently conflicting results in the literature, the possibility of pseudotransduction must be considered, especially when cell lysate stocks of AAV vectors have been employed. This artifact can be avoided by further vector purification.


[Epidemiological study of women adults with mixed urinary incontinence in China].
To investigate the prevalence and the epidemiological factors of female mixed urinary incontinence (MUI) in China. In February to July 2006, 19 024 subjects aged over 20 years old in 6 Chinese regions including Northwest, Southwest, Northern China, Eastern China, Northeast and South China were selected. Questionnaires were used to investigate the general characters and the lower urinary tract symptoms in these subjects. The overall prevalence of mixed urinary incontinence was 9.4% among these women and it increased with advancing age. In multiple logistic models, age, vaginal delivery, constipation, pelvic organ prolapse, chronic pelvic pain, respiratory system disease, menstrual disorder, urinary system disease, alcohol consumption, pelvic surgery, obesity as well as high educational level were independent risk factors for mixed urinary incontinence. The prevalence of MUI increases with advancing age. Vaginal delivery, constipation and pelvic organ prolapse are risk factors for mixed urinary incontinence in China while high educational level is a protective factor.


[Post-operative lumbar myelogram. Morphology and indications for repeat examinations in patients with disc prolapse (author's transl)].
The morphology and indications for performing post-operative contrast examinations have been analysed in 131 myelograms. Leptomeningeal reactions and adhesions were found in varying degrees of severity in 34 to 75% of post-operative cases; it proved difficult to correlate this finding with the neurological features. The value of repeat myelograms is much reduced after surgery or after previous contrast examinations. It is probable that this is due in part to tissue changes resulting from the surgery or from a proliferative reaction induced by the contrast medium.


Zwitterionic dithiocarboxylates derived from N-heterocyclic carbenes: coordination to gold surfaces.
The zwitterionic dithiocarboxylates 1(+)-CS(2)(-)-4(+)-CS(2)(-) were prepared by reacting the corresponding N-heterocyclic carbenes 1,3-bis(2,6-diisoproylphenyl)imidazol-2-ylidene (1), 1,3-diisopropylimidazol-2-ylidene (2), 1,3-dibenzylimidazol-2-ylidene (3) and 1,3-diethylbenzimidazol-2-ylidene (4) with CS(2). In the latter two cases, the corresponding N-heterocylic carbene was generated in situ. Compounds 2(+)-CS(2)(-)-4(+)-CS(2)(-) were structurally characterised by single-crystal X-ray diffraction studies. The chemisorption of these zwitterionic dithiocarboxylates on solid gold substrates was investigated in situ and in real time by optical second harmonic generation (SHG). The resulting thin films were exemplarily characterised by near-edge X-ray absorption fine structure (NEXAFS) spectroscopy and X-ray photoelectron spectroscopy (XPS) in the case of 1(+)-CS(2)(-) and 2(+)-CS(2)(-), revealing the formation of almost contamination-free self-assembled monolayers, which exhibit a remarkable degree of orientational order.


The sexual behaviour of physically disabled adolescents.
Risky sexual behaviour is a major factor contributing to the increasing prevalence of HIV/AIDS in South Africa. A large national survey of adolescent's sexual behaviour was undertaken in 2002, however adolescents with disabilities were excluded from this study. The aim of this study is to compare the sexual behaviours of adolescents with physical disabilities to those of their non-disabled peers. A cross-sectional sample was drawn from learners with physical disabilities between grades 8 and 9 in Cape Town. Data were collected using the South African youth risk behaviour survey adapted by the medical research council of South Africa. There were responses from 91 participants, of which 56% were males. Approximately, one quarter of the special school sample reported sexual activity compared with one third of the national sample; the difference approached significance. As with the national sample, relatively few adolescents thought they were likely to contract HIV in their lifetime (12%). Fifty percent of the sample claimed that they were able to protect themselves against contracting HIV compared with 66% of the adolescents without disability. The percentage reporting two or more sexual partners in the special schools (27%) was about half that of the national sample (53%). There was little difference in the percentages reporting substance abuse related to sexual activity (14% compared with 15%) and the national sample reported more regularly use of condoms (Special school 18% compared with 25%). Disabled adolescents are indulging in risky sexual behaviours, and are at equal risk as their non-disabled peers of developing HIV. Adolescents with disability must not be excluded from main stream research and health promotion activities specifically related to sex education.