Pterostilbene protects against UVB-induced photo-damage through a phosphatidylinositol-3-kinase-dependent Nrf2/ARE pathway in human keratinocytes.
Ultraviolet B (UVB) irradiation is the initial etiological factor for various skin disorders, including erythema, sunburn, photoaging, and photocarcinogenesis. Pterostilbene (Pter) displayed remarkable antioxidant, anti-inflammatory, and anticarcinogenic activities. This study aimed to investigate the effective mechanism of Pter against UVB-induced photodamage in immortalized human keratinocytes. Human keratinocytes were pretreated with Pter (5 and 10 μM) for 24 h prior to UVB irradiation (300 mJ/cm2). Harvested cells were analyzed by MTT, DCFH-DA, comet, western blotting, luciferase promoter, small interference RNA transfection, and quantitative real-time polymerase chain reaction assay. Pter significantly attenuated UVB-induced cell death and reactive oxygen species (ROS) generation, and effectively increased nuclear translocation of NF-E2-related factor-2 (Nrf2), expression of Nrf2-dependent antioxidant enzymes, and DNA repair activity. Moreover, the protective effects of Pter were abolished by small interference RNA-mediated Nrf2 silencing. Furthermore, Pter was also found to induce the phosphorylation of Nrf2 and the known phosphatidylinositol-3-kinase (PI3K) phosphorylated kinase, Akt. The specific inhibitor of PI3K, LY294002, successfully abrogated Pter-induced Nrf2 phosphorylation, activation of Nrf2-antioxidant response element pathway, ROS scavenging ability, and DNA repair activity. The present study indicated that Pter effectively protected against UVB-induced photodamage by increasing endogenous defense mechanisms, scavenging UVB-induced ROS, and aiding in damaged DNA repair through a PI3K-dependent activation of Nrf2/ARE pathway.


4D MUSIC CMR: value-based imaging of neonates and infants with congenital heart disease.
4D Multiphase Steady State Imaging with Contrast (MUSIC) acquires high-resolution volumetric images of the beating heart during uninterrupted ventilation. We aim to evaluate the diagnostic performance and clinical impact of 4D MUSIC in a cohort of neonates and infants with congenital heart disease (CHD). Forty consecutive neonates and infants with CHD (age range 2 days to 2 years, weight 1 to 13 kg) underwent 3.0 T CMR with ferumoxytol enhancement (FE) at a single institution. Independently, two readers graded the diagnostic image quality of intra-cardiac structures and related vascular segments on FE-MUSIC and breath held FE-CMRA images using a four-point scale. Correlation of the CMR findings with surgery and other imaging modalities was performed in all patients. Clinical impact was evaluated in consensus with referring surgeons and cardiologists. One point was given for each of five key outcome measures: 1) change in overall management, 2) change in surgical approach, 3) reduction in the need for diagnostic catheterization, 4) improved assessment of risk-to-benefit for planned intervention and discussion with parents, 5) accurate pre-procedural roadmap. All FE-CMR studies were completed successfully, safely and without adverse events. On a four-point scale, the average FE-MUSIC image quality scores were >3.5 for intra-cardiac structures and >3.0 for coronary arteries. Intra-cardiac morphology and vascular anatomy were well visualized with good interobserver agreement (r = 0.46). Correspondence between the findings on MUSIC, surgery, correlative imaging and autopsy was excellent. The average clinical impact score was 4.2 ± 0.9. In five patients with discordant findings on echo/MUSIC (n = 5) and catheter angiography/MUSIC (n = 1), findings on FE-MUSIC were shown to be accurate at autopsy (n = 1) and surgery (n = 4). The decision to undertake biventricular vs univentricular repair was amended in 2 patients based on FE-MUSIC findings. Plans for surgical approaches which would have involved circulatory arrest were amended in two of 28 surgical cases. In all 28 cases requiring procedural intervention, FE-MUSIC provided accurate dynamic 3D roadmaps and more confident risk-to-benefit assessments for proposed interventions. FE-MUSIC CMR has high clinical impact by providing accurate, high quality, simple and safe dynamic 3D imaging of cardiac and vascular anatomy in neonates and infants with CHD. The findings influenced patient management in a positive manner.


Bending-activated biotensegrity structure enables female Megarhyssa to cross the barrier of Euler's critical force.
The parasitic female Megarhyssa has a hair-like ovipositor capable of withstanding a penetration force 10 times greater than Euler's critical force, using a reciprocating penetration method. Understanding and replicating this penetration mechanism may notably broaden the application scenarios of artificial slender elements. Here, we show that the Megarhyssa's stretched intersegmental membrane and precurved abdomen activate the multipart ovipositor as a biotensegrity structure. The ovipositor's first and second valvulae alternately retract and protract, with each retracted valvula forming a tension network to support the other under compression, resulting in an exponentially increased critical force. We validated this mechanism in a multipart flexible microneedle that withstood a penetration force of 2.5× Euler's critical force and in a lightweight industrial robot that achieved intrinsic safety through its ideal dual-stiffness characteristic. This finding could potentially elucidate the high efficiency of insect probes and inspire more efficient and safer engineering designs.


Lysosomal integral membrane protein-2: a new player in lysosome-related pathology.
Lysosomes require the presence of many specialized proteins to facilitate their roles in cellular maintenance. One such protein that has proven to be an important player in the lysosomal field is lysosomal integral membrane protein-2 (LIMP-2), encoded by the gene SCARB2. LIMP-2 is required for the normal biogenesis and maintenance of lysosomes and endosomes and has been identified as the specific receptor for glucocerebrosidase, the enzyme deficient in Gaucher disease. Research into LIMP-2 and the SCARB2 gene indicate that it may be a factor contributing to the clinical heterogeneity seen among patients with Gaucher disease. Mutations in SCARB2 have also been identified as the cause of action myoclonus renal failure (AMRF), and in some cases progressive myoclonic epilepsy. A total of 14 disease-causing SCARB2 mutations have been identified to date. The role of LIMP-2 in human pathology has expanded with its identification as a component of the intercalated disk in cardiac muscle and as a receptor for specific enteroviruses, two unanticipated findings that reaffirm the myriad roles of lysosomal proteins. Studies into the full impact of LIMP-2 deficiency and the LIMP2/glucocerebrosidase molecular pathway will lead to a better understanding of disease pathogenesis in Gaucher disease and AMRF, and to new insights into lysosomal processing, trafficking and function.


Bayesian spatial modelling of intimate partner violence and associated factors among adult women and men: evidence from 2019/2020 Rwanda Demographic and Health Survey.
Intimate partner violence (IPV) remains a global public health concern for both men and women. Spatial mapping and clustering analysis can reveal subtle patterns in IPV occurrences but are yet to be explored in Rwanda, especially at a lower small-area scale. This study seeks to examine the spatial distribution, patterns, and associated factors of IPV among men and women in Rwanda. This was a secondary data analysis of the 2019/2020 Rwanda Demographic and Health Survey (RDHS) individual-level data set for 1947 women aged 15-49 years and 1371 men aged 15-59 years. A spatially structured additive logistic regression model was used to assess risk factors for IPV while adjusting for spatial effects. The district-level spatial model was adjusted for fixed covariate effects and was implemented using a fully Bayesian inference within the generalized additive mixed effects framework. IPV prevalence amongst women was 45.9% (95% Confidence interval (CI): 43.4-48.5%) while that for men was 18.4% (95% CI: 16.2-20.9%). Using a bivariate choropleth, IPV perpetrated against women was higher in the North-Western districts of Rwanda whereas for men it was shown to be more prevalent in the Southern districts. A few districts presented high IPV for both men and women. The spatial structured additive logistic model revealed higher odds for IPV against women mainly in the North-western districts and the spatial effects were dominated by spatially structured effects contributing 64%. Higher odds of IPV were observed for men in the Southern districts of Rwanda and spatial effects were dominated by district heterogeneity accounting for 62%. There were no statistically significant district clusters for IPV in both men or women. Women with partners who consume alcohol, and with controlling partners were at significantly higher odds of IPV while those in rich households and making financial decisions together with partners were at lower odds of experiencing IPV. Campaigns against IPV should be strengthened, especially in the North-Western and Southern parts of Rwanda. In addition, the promotion of girl-child education and empowerment of women can potentially reduce IPV against women and girls. Furthermore, couples should be trained on making financial decisions together. In conclusion, the implementation of policies and interventions that discourage alcohol consumption and control behaviour, especially among men, should be rolled out.


Emergence of permanently differentiated cell clones in a human colonic cancer cell line in culture after treatment with sodium butyrate.
The human colonic cancer cell line HT29 is undifferentiated in standard culture conditions (Dulbecco's medium:10% fetal bovine serum). These cells were cultured in 5 mM sodium butyrate for 9 days; then they were trypsinized and subcultured in sodium butyrate for an additional 14 days. Multinucleation occurred during this second phase of the treatment. The cells were then transferred to standard medium and multinucleation disappeared. Morphological changes appeared 10 to 12 days after return to standard culture conditions; some cells flattened and became more adherent to the bottom of the flasks. These altered cells divided actively and formed "flat foci" interspersed among the densely packed undifferentiated HT29 cells. This altered phenotype persists after more than 24 months of culture in standard medium. Clonal cell lines were established from these flat foci-forming cells and characterized. These clonal lines exhibited morphological cell polarity defined by an apical cell surface separated by junctional complexes from the basolateral cell surface. Functional differentiation did also occur since some clonal lines formed domes representing active transepithelial transport, and others exhibited massive mucus secretion. In conclusion, our findings indicate that permanently differentiated cell populations emerged in a colonic cancer cell line after sodium butyrate treatment. These new clonal lines will be useful in future models for the study of differentiation programs of both normal and cancerous colonic cells.


Concurrent decreases in the prevalence of wheezing and Ascaris infection among 5-year-old children in rural Bangladesh and their regulatory T cell immunity after the implementation of a national deworming program.
Epidemiological research on the prevalence of asthma and helminthic infections in various countries has led to the hypothesis that helminthic infections protect against asthma by suppressing the host's immune response. This study was conducted to elucidate whether decreased Ascaris infection following a national deworming program was associated with increased recurrent wheezing among rural Bangladeshi children and to test their anti-inflammatory immunity. This nested case-control study was conducted from December 2015 to October 2016 in the rural service area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Of the 1800 5-year old children randomly selected for the study, informed consent was obtained from the guardians of 1658 children. Data were collected using a semistructured questionnaire adopted from the International Study of Asthma and Allergies in Childhood and blood samples for the analysis of regulatory T (Treg) cell immune responses and the balance between Th1 and Th2 immunity in Ascaris infections. A total of 145 children were found to have wheezing, yielding a prevalence rate of 8.7%, which was significantly lower than the rate found in 2001 (16.2%, P < .001); Ascaris infection also decreased from 2001 to 2016. The 127 wheezing children who agreed to participate further were compared to 114 randomly selected never-wheezing children. Wheezing had a significant positive association with antibiotic use, history of pneumonia, parents' history of asthma, and Ascaris infection; children with Ascaris infection were twice as likely to have wheezing (adjusted odds ratio = 2.31, P = .053). Flow cytometry found no significant differences in the rates of Th1, Th2, and CD4 + CD25 + CD127low cells by the wheezing group. Ascaris infection had a positive rather than a negative association with wheezing and the rates of wheezing and Ascaris infections both decreased from 2001 to 2016. These findings undermines the hypothesis that such infections provide protection against asthma.


The effect of left atrial appendage closure on heart failure biomarkers: A PRAGUE-17 trial subanalysis.
The randomized PRAGUE-17 trial demonstrated noninferiority of left atrial appendage closure (LAAC) to non-vitamin K anticoagulants (NOACs) for the prevention of major cardiovascular or cerebrovascular events. However, the left atrial appendage is an important source of natriuretic peptides and plays a role in left atrial reservoir function. Changes of heart failure (HF) biomarkers after LAAC compared to NOAC has not been studied. The aim of the study was to compare the changes in concentrations of HF biomarkers between LAAC and NOAC patients. Of 402 patients randomized in the PRAGUE-17 trial, biomarkers were analyzed in 144 patients (73 in the NOAC and 71 in the LAAC group). Both groups had similar baseline characteristics. Serum concentration of NT-proBNP, NT-proANP, Galectin-3, and GDF-15 were measured at baseline (before the procedure in the LAAC group), at the 6-month (and at 24-month for NT-proBNP) follow-up timepoint. There were no significant differences in baseline, 6 month, and delta (δ = baseline - 6 month) concentrations of NT-proANP between the groups (NOAC: baseline 2.6 [0.5; 4.9], 6-month 3.1 [1.8; 4.8], p = .068; LAAC: baseline 3.3 [1.1; 4.6], 6-month 2.6 [0.9; 5.3], p = .51; p value for δ in concentrations between groups = 0.42). Similarly, there were no significant differences in baseline, 6, 24 months, and delta concentrations of NT-proBNP between the groups (NOAC: baseline 461.0 [113.5; 1342.0], 6 month 440.0 [120.5; 1291.5], 24 month 798 [274; 2236], p = .39; LAAC: baseline 421.0 [100.0; 1320.0], 6 month 601.0 [145.0; 1230.0], 24 month 855 [410; 1367], p = .28; p value for δ in concentrations between groups = 0.73 at 6 months, and 0.58 at 24 months). Finally, no significant differences were present in baseline, 6 month, and δ concentrations of Galectin-3 and GDF-15 between the two groups. LAAC did not significantly influence the levels of HF biomarkers 6 months after the procedure.


Overexpressed recombinant quorum quenching lactonase reduces the virulence, motility and biofilm formation of multidrug-resistant Pseudomonas aeruginosa clinical isolates.
The increasing occurrence of resistance among Pseudomonas aeruginosa clinical isolates necessitates finding alternatives to antibiotics for controlling the infection of such pathogenic bacteria. In this study, lactonase gene ahl-1 from Bacillus weihenstephanensis isolate-P65 was successfully cloned and expressed in Escherichia coli BL21 (DE3) under the control of T7 promoter for utilizing its quorum quenching activity against three multidrug-resistant (MDR) P. aeruginosa clinical isolates. The biological activity of the overexpressed lactonase enzyme (Ahl-1), tested using a synthetic signal and Chromobacterium violaceum CV026 as a biosensor, displayed good catalytic activity using hexanoyl homoserine lactone (HHL) as a substrate and Chromobacterium violaceum (CV026) as a biosensor (77.2 and 133 nm min-1 for the crude and the purified Ahl-lactonase enzymes, respectively). Upon challenging its ability to inhibit the virulence of three MDR P. aeruginosa clinical isolates, recombinant Ahl-1 successfully prevented the accumulation of acylhomoserine lactone signals resulting in a significant reduction in the investigated virulence determinants; protease (from 40 up to 75.5%), pyocyanin (48-75.9%), and rhamnolipids (52.7-63.4%) (P value < 0.05). Ahl-1 also displayed significant inhibitory activities on the swarming motility and biofilm formation of the three tested MDR P. aeruginosa clinical isolates (P value < 0.05). Consequently, Ahl-1 lactonase enzyme in this study is considered a promising therapeutic agent to inhibit P. aeruginosa pathogenicity with no fear of emergence of resistance.


Effects of catheter orifice configuration (triple-hole versus end-hole) in continuous infraclavicular brachial plexus block on analgesia after upper limb surgery.
The configuration of a nerve block catheter may affect the local anesthetic spread in epidural analgesia and continuous peripheral nerve blocks. This prospective and randomized study aims to compare the multi-orifice nerve block catheter with an end-hole catheter in ultrasound-guided continuous infraclavicular brachial plexus block (BPB) in terms of providing postoperative analgesia for the orthopedic upper limb surgery below the shoulder. The primary outcome measure was mean pain scores. Secondary outcome measures were the consumption of rescue analgesic and the amount of local anesthetics delivered by a Patient-Controlled Analgesia (PCA) device. A total of 58 adult patients who underwent orthopedic upper limb surgery below the shoulder were randomly assigned into two groups: group end-hole catheter (EHC) (n=31) and group multi-orifice catheter (MOC) (n=27). All patients received a single-shot infraclavicular BPB using 100 mg lidocaine 2% and 75 mg bupivacaine 0.5% administrated through a Tuohy needle. Then, a multi-orifice (triple-hole) nerve catheter was placed in the group MOC and an end-hole (one-hole) catheter in the group EHC at the same location. Bupivacaine 0.125% was infused through the catheters via PCA (infusion rate: 2 mlh-1, automated regular bolus: 5 mlh-1, patient-controlled bolus: 3 ml, lock-out time: 1 hour, 4 hours limit: 40 ml). Pain intensity was evaluated using a visual analogue scale (VAS). Mean VAS scores were higher in group EHC than group MOC in the first postoperative day (p=0.001). Mean rescue analgesic consumption, the number of bolus demand on PCA, PCA bolus demand dose, and total PCA dose were higher in group EHC than group MOC during the first postoperative day (p<0.05). It is concluded that the use of MHC is more effective than EHC for continuous infraclavicular brachial plexus blocks in providing postoperative pain relief during the first 24 hours.


Computational evaluation of sparse coding on off-axis electron holograms: comparison between charge-coupled device and direct-detection device cameras.
The effectiveness of sparse coding for image inpainting and denoising of off-axis electron holograms was examined computationally based on hologram simulations according to considerations of two types of electron detectors, namely charge-coupled device (CCD) and direct-detection device (DDD) cameras. In this simulation, we used a simple-phase object with a phase step such as a semiconductor p-n junction and assumed that the holograms recorded by the CCD camera include shot noise, dark-current noise and read-out noise, while those recorded by the DDD camera include only shot noise. Simulated holograms with various electron doses were sparsely coded. Even though interference fringes cannot be recognized in the simulated CCD and DDD holograms when subjected to electron doses (per pixel) equal to 1 and 0.01, respectively, both the corresponding sparse-coded holograms exhibit meaningful interference fringes. We demonstrate that a combination of the DDD camera and sparse coding reduces the requisite dose used to obtain holograms to values less than one-thousandth compared with the CCD camera without image postprocessing. This combination is expected to generate lower-dose and/or higher-speed electron holography.


[Amplification of c-myc proto-oncogene in primary tumors, metastases and blood leukocytes of patients with ovarian cancer].
The structure of DNA sequences homologous to the viral myc oncogene from ovarian tumours, intact tissues and the same patients peripheral blood leukocytes has been studied. The Southern blot analysis of malignant tumour DNA reveals amplification of c-myc protooncogene of 3 from 11 patients. Metastases DNAs of two from those patients also contain multiple copies of c-myc. No myc gene amplification has been detected in 6 examined benign ovarian tumours. The presence of extra copies of myc-related sequences has been shown in two from three DNA samples from peripheral blood leukocytes of patients with ovarian cancer.


The Lbc gene promotes differentiation of chicken embryo stem cell into spermatogonial stem cells via the regulation of transcriptional factor Hoxa5.
Recently, the surface marker genes of spermatogonial stem cells (SSCs) were increasingly excavated and verified. However, few studies focused on the key genes involved in the regulation of SSCs differentiation. Our laboratory has screened the Lbc gene (GenBank accession number: XM_429585.3), which is specifically expressed on the SSCs. The aim of this study is to investigate the function of Lbc and its regulatory mechanism for SSCs. The indirect immunofluorescence assay (IFA) showed that Lbc was located in both nucleus and cytoplasm. Lbc was also overexpressed and knocked out both in vitro and in vivo to verify its function in SSCs, respectively. As a result, the overexpressed Lbc could promote the formation of spermatogonial stem cells like cells (SSCs-like), while the deficiency of Lbc blocked the formation of SSCs-like. We also identified the core region of Lbc promoter that located into the upstream of the transcription initiation site -247 to -2bp. Moreover, the activity of Lbc promoter could be increased by histone acetylation which is leading to the higher expression of Lbc. When we mutated the transcription factor HOXA5 and SOX10 that bound to the core region of Lbc promoter, HOXA5 could reduce the transcription activity of Lbc whereas the SOX10 was not. Currently, we found Lbc is a new specific marker of SSCs. This gene can be modified by histone acetylated and promote the formation of chicken SSCs via the transcription factor HOXA5. The present research will lay the foundation for further study on the regulatory mechanism of SSCs.


Onset of quantum chaos in one-dimensional bosonic and fermionic systems and its relation to thermalization.
By means of full exact diagonalization, we study level statistics and the structure of the eigenvectors of one-dimensional gapless bosonic and fermionic systems across the transition from integrability to quantum chaos. These systems are integrable in the presence of only nearest-neighbor terms, whereas the addition of next-nearest-neighbor hopping and interaction may lead to the onset of chaos. We show that the strength of the next-nearest-neighbor terms required to observe clear signatures of nonintegrability is inversely proportional to the system size. Interestingly, the transition to chaos is also seen to depend on particle statistics, with bosons responding first to the integrability breaking terms. In addition, we discuss the use of delocalization measures as main indicators for the crossover from integrability to chaos and the consequent viability of quantum thermalization in isolated systems.


A novel noninvasive ocular surface analyzer for the assessment of dry eye with Meibomian gland dysfunction.
Meibomian gland dysfunction (MGD) is a major cause of dry eye, and the purpose of the present study was to evaluate the differences between dry eye patients with MGD and controls using a novel noninvasive ocular surface analyzer. A total of 33 dry eye patients with MGD and 31 controls were enrolled in the present study. Testing included administration of the Ocular Surface Disease Index (OSDI), followed by Keratogragh 5M (Oculus, Wetzlar, Germany), measurements of the noninvasive tear film break-up times (NITBUTs), the first tear film break-up point and the morphology of meibomian gland. Meibomian gland loss (MGL) on the upper lid was evaluated using noncontact meibography. The first NITBUT (NITBUTf) was significantly shorter than the average NITBUT (NITBUTav; Mann-Whitney U-test, P<0.01). There was a weak negative Spearman correlation between NITBUTf and OSDI (rs=-0.251, P=0.046) as well as between NITBUTav and OSDI (rs=-0.250, P=0.046). Furthermore, MGL showed a statistically significant Spearman correlation with OSDI (rs=0.562; P<0.01). In the MGD group, NITBUTf was significantly shorter (P<0.01), and MGL and OSDI score were significantly greater (P<0.01 and <0.01, respectively) than in the control group. In the MGD group, the first tear film break-up point was most frequently located in the inferonasal quadrant, while it was most frequently located in the supertemporal quadrant in the control group, and there was a significant difference with this regard (χ2=3.937, P=0.047). In the MGD group, there were significantly more breakups in the lower quadrant than in the upper quadrant (P=0.011), whereas no differences in the number of breakups in each quadrant were observed in the control group (P=0.429). Furthermore, there was no significant difference in the breakups in the lower quadrants of the two groups (χ2=0.525, P=0.469). In the MGD group, there were significantly more breakups in the lower quadrant than in the upper quadrant (P=0.011), whereas no differences in the number of breakups in each quadrant were observed in the control group (P=0.429). Furthermore, there was no significant difference in the breakups in the lower quadrants of the two groups (χ2=0.525, P=0.469). As the NITBUTs showed only a weak correlation with OSDI, they may not be a strong indicator of the OSDI. However, MGL indicated changes of meibomian gland morphology in the MGD group and the first tear film break-up point was likely located in the inferonasal quadrant in the MGD group.


When roles within interpreter-mediated psychiatric consultations speak louder than words.
In South Africa, clinicians working in public psychiatric hospitals are mainly fluent in English and Afrikaans, while the majority of patients are not proficient in these languages. Due to a lack of professional interpreting services, informal, ad hoc interpreters are commonly employed in public psychiatric hospitals. We collected data on language practices in public psychiatric care in South Africa, and provide a detailed account of what happens when bilingual health care workers and cleaners haphazardly take on the additional role of interpreter. Data were collected during 2010 at a public psychiatric hospital in the Western Cape, South Africa. Thirteen interpreter-mediated psychiatric consultations were video-recorded, and 18 audio-recorded semi-structured interviews were conducted with the interpreters and clinicians who participated in the interpreter-mediated psychiatric consultations. Patients were proficient in isiXhosa (one of the 11 official languages of South Africa), the clinicians (all registrars) were first language English or Afrikaans speakers, while the health care workers (nurses and social workers) and cleaners were fluent in both the patients' and clinician's language. Our findings suggest that interpreters took on the following four roles during the interpreter-mediated psychiatric consultations: regulating turn-taking, cultural broker, gatekeeper and advocate. Our findings suggest that, despite interpreters and clinicians having the patient's best interests at heart, it is the patient's voice that becomes lost while the clinician and interpreter negotiate the roles played by each party.


The future of our profession: a true-false test.
You are supposed to draw the conclusions and take the actions. My own belief is that we have a continuing obligation to provide a high quality education to as many qualified applicants as we effectively can. At this time we enjoy a unique opportunity that combines large numbers of qualified applicants with a substantial number of excellent training programs, and an unprecedented public demand for more and better health care. We must state clearly the public need for ophthalmologic eye care and must provide the manpower to deliver such care. Most importantly, we must not forget what it's all about: The philosophy of Mount Carmel is service to God through service to man, a service which is based on a belief in, and love for God. This love provides the finest medical and spiritual care for each patient without discrimination. The primary objective is to relieve suffering and to promote and to restore health in a Christian manner, which demands competence, mercy, love, and respect.


Somatostatin receptor subtypes: targeting functional and therapeutic specificity.
Somatostatin is a regulatory peptide involved in a wide variety of biological functions throughout the body. A key physiological question, as well as the challenge to developing somatostatin-based therapeutics, is how functional specificity can be conferred in such a widespread, multifunctional hormonal system. With the discovery of distinct subtypes of the somatostatin receptor, we have attempted to elucidate the manner in which somatostatin selectively regulates specific biological functions using panels of somatostatin analogs that have been fully characterized for their unique selectivity and specificity for the various receptor subtypes. By testing these selective analogs in well-established biological assay systems, we and our collaborators have revealed functional interactions between the somatostatin receptor subtypes that can either potentiate or antagonize the cellular response to somatostatin. These observations have resulted in several novel concepts for treating acromegaly that should offer greater efficacy to a larger percentage of patients than current therapeutic options. Further, these studies are providing evidence of interaction between the somatostatin receptor subtypes and receptors of other G-protein-coupled receptor families. These various levels of interaction provide a means by which the cellular response to somatostatin can be exquisitely controlled and modified by both physiological status and disease. Greater understanding of these interactions will provide the conceptual basis for future therapeutics with enhanced efficacy and with greater cellular and functional specificity.


Effects of cultivar and culture conditions on gamma-aminobutyric acid accumulation in germinated fava beans (Vicia faba L.).
High levels of gamma-aminobutyric acid (GABA) accumulate in plant tissues under various stresses. GABA accumulation is also influenced by cultivar. This aim of this study was to select the most promising cultivar of fava bean for GABA accumulation and to optimise the culture conditions for GABA production in germinated fava beans by response surface methodology based on central composite design (CCD). GABA content and glutamate decarboxylase activity in germinated seeds of cultivar S2 were significantly higher than those in other cultivars (P < 0.05). A significant negative correlation (r = -0.765, P < 0.05) between germination percentage and 1000-kernel weight was observed. There was a linear relationship between GABA content and sprout length (R(2) = 0.816). The regression model fitted to the experimental data of CCD was valid in predicting GABA production in germinated fava beans. Temperature and pH value of the culture solution had significant effects on GABA content in germinated fava beans. Under optimal culture conditions (33.6 degrees C, pH 3.19 and an air flow rate of 1.19 L min(-1)), GABA content reached up to 2.41 g kg(-1) dry weight, about 48 times that in raw seeds. Germinated fava bean is a good resource of GABA-rich food. Both cultivar and culture conditions have significant effects on GABA production.


Bile acids and their effects on diabetes.
Diabetes is a widespread, rapidly increasing metabolic disease that is driven by hyperglycemia. Early glycemic control is of primary importance to avoid vascular complications including development of retinal disorders leading to blindness, end-stage renal disease, and accelerated atherosclerosis with a higher risk of myocardial infarction, stroke and limb amputations. Even after hyperglycemia has been brought under control, "metabolic memory," a cluster of irreversible metabolic changes that allow diabetes to progress, may persist depending on the duration of hyperglycemia. Manipulation of bile acid (BA) receptors and the BA pool have been shown to be useful in establishing glycemic control in diabetes due to their ability to regulate energy metabolism by binding and activating nuclear transcription factors such as farnesoid X receptor (FXR) in liver and intestine as well as the G-protein coupled receptor, TGR5, in enteroendocrine cells and pancreatic β-cells. The downstream targets of BA activated FXR, FGF15/21, are also important for glucose/insulin homeostasis. In this review we will discuss the effect of BAs on glucose and lipid metabolism and explore recent research on establishing glycemic control in diabetes through the manipulation of BAs and their receptors in the liver, intestine and pancreas, alteration of the enterohepatic circulation, bariatric surgery and alignment of circadian rhythms.


Combination therapy design for maximizing sensitivity and minimizing toxicity.
Design of personalized targeted therapies involve modeling of patient sensitivity to various drugs and drug combinations. Majority of studies evaluate the sensitivity of tumor cells to targeted drugs without modeling the effect of the drugs on normal cells. In this article, we consider the individual modeling of drug responses to tumor and normal cells and utilize them to design targeted combination therapies that maximize sensitivity over tumor cells and minimize toxicity over normal cells. The problem is formulated as maximizing sensitivity over tumor cell models while maintaining sensitivity below a threshold over normal cell models. We utilize the constrained structure of tumor proliferation models to design an accelerated lexicographic search algorithm for generating the optimal solution. For comparison purposes, we also designed two suboptimal search algorithms based on evolutionary algorithms and hill-climbing based techniques. Results over synthetic models and models generated from Genomics of Drug Sensitivity in Cancer database shows the ability of the proposed algorithms to arrive at optimal or close to optimal solutions in significantly lower number of steps as compared to exhaustive search. We also present the theoretical analysis of the expected number of comparisons required for the proposed Lexicographic search that compare favorably with the observed number of computations. The proposed algorithms provide a framework for design of combination therapy that tackles tumor heterogeneity while satisfying toxicity constraints.


Decision Support System for Variable Rate Irrigation Based on UAV Multispectral Remote Sensing.
Rational utilization of water resources is one of the major methods of water conservation. There are significant differences in the irrigation needs of different agricultural fields because of their spatial variability. Therefore, a decision support system for variable rate irrigation (DSS-VRI) by center pivot was developed. This system can process multi-spectral images taken by unmanned aerial vehicles (UAVs) and obtain the vegetation index (VI). The crop evapotranspiration model (ETc) and crop water stress index (CWSI) were obtained from their established relationships with the VIs. The inputs to the fuzzy inference system were constituted with ETc, CWSI and precipitation. To provide guidance for users, the duty-cycle control map was outputted using ambiguity resolution. The control command contained in the map adjusted the duty cycle of the solenoid valve, and then changed the irrigation amount. A water stress experiment was designed to verify the rationality of the DSS-VRI. The results showed that the more severe water stress is, the more irrigation is obtained, consistent with the expected results. Meanwhile, a user-friendly software interface was developed to implement the DSS-VRI function.


Sensitive infant caregiving among the rural Gusii in Kenya.
The Gusii in rural Kenya represent a particularly interesting community for the study of sensitivity, as they have previously been described as not showing sensitive care. This study focuses on the observation of sensitivity in seven families with a 7-to 23-month-old infant, with extensive naturalistic video observations (ca. 2-4 h per infant) in a multiple caregiver setting, and potential co-existing harsh parenting practices. The average score for received sensitive caregiving was rather low at 5.3, but four out of seven infants were rated as receiving at least adequately sensitive care. Sensitivity was mostly expressed non-verbally in the form of (subtle) physical responsiveness by a variety of caregivers, and seen to a high extent during infant feeding. Insensitivity was seen when caregivers were occupied with chores, and during infant bathing. Results are discussed in terms of the nature of sensitive caregiving among the Gusii, and factors that might explain within-group differences.


Magnetic Resonance Imaging Manifestations of Pediatric Purulent Meningitis Based on Immune Clustering Algorithm.
The purpose of this study was to analyze the diagnostic value of magnetic resonance imaging (MRI) based on the immune clustering algorithm (ICA) in children with purulent meningitis. In this study, 235 children with suspected pediatric purulent meningitis (PPM) were routinely scanned, and the artificial immune algorithm (AIA) and ICA were applied to image processing. In order to quantitatively analyze the accuracy and precision of the processed image, precision rate was introduced as the evaluation of accuracy, and the True Positive Vis Fox, False Negative Vis Fo, and False Positive Vis Fo were selected as the evaluation indicators. After comparison, the accuracy, sensitivity, and specificity of ICA detection were higher than those of AIA and conventional plain scanning, and the differences were statistically obvious (P < 0.05). Comparison on image display effects showed that compared with AIA, the image processed by the ICA algorithm constructed in this study showed the highest definition and contrast and the best denoising effect and image quality, showing a statistically obvious difference (P < 0.05). All in all, the display effect of MRI images of pediatric purulent meningitis based on ICA was more accurate and clearer than that of the traditional image processing, and it can provide a more accurate auxiliary basis in the diagnosis of lesion details. It also showed a higher clinical value for the development of a diagnosis and treatment plan for complicated PPM.


Hydrological properties of a clay loam soil after long-term cattle manure application.
Limited information exists on the effect of long-term application of beef cattle (Bos taurus) manure on soil hydrological properties in the Great Plains region of North America. A site on a clay loam soil (Typic Haploboroll) was used to examine the effect of manure addition on selected soil hydrological properties in 1997 and 1998. The manure was annually applied in the fall for 24 yr at one, two, and three times the recommended rates (in 1973) under dryland (0, 30, 60, and 90 Mg ha(-1) wet basis) and irrigation (0, 60, 120, and 180 Mg ha(-1)). Manure significantly (P < or = 0.05) increased soil water retention (0-5 and 10-15 cm) by 5 to 48% compared with the control at most potentials between 0 and -1500 kPa. Field soil water content (0-5 and 10-15 cm) was increased by 10 to 22% in the summers of 1997 and 1998. Manure increased ponded infiltration by more than 200% at 90 Mg ha(-1) under dryland (1998) and at rates > or = 120 Mg ha(-1) under irrigation (1997). Field-saturated hydraulic conductivity (Kfs) of surface soil (1-cm depth) was significantly increased by 76 to 128% under dryland (1998) and irrigation (1997), as were number of pores > 1120 microm in diameter (37-128% increase). In contrast, manure rate had little or no effect on unsaturated hydraulic conductivity [K(psi)] values (-0.3, -0.5, -0.7, and -1.0 kPa) in 1997 and 1998. Overall, soil hydrological parameters generally had a neutral or positive response to 24 yr of annual manure addition.


The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells.
Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle. Suppression of CST induces telomere instabilities including telomere fragility and elevates telomeric DNA recombination, leading to telomere dysfunction. In addition, CST deficiency significantly diminishes the abundance of extrachromosomal circular telomere DNA known as C-circles and t-circles. Suppression of CST also results in multinucleation in ALT cells and impairs cell proliferation. Our findings imply that the CST complex plays an important role in regulating telomere maintenance in ALT cells.


Burden of inherited ichthyosis: a French national survey.
Moderate to severe ichthyosis is known to have a significant impact on quality of life. A French national survey was performed to describe in more detail how ichthyosis impacts the patients' lives. A questionnaire specifically dedicated to ichthyosis was distributed to patients followed in hospital expert centres or members of the French association of patients. A total of 241 questionnaires were completed and returned (response ratio: 29% for children and 71% for adults). A negative impact of ichthyosis was obvious in terms of domestic life (skin care, housework, clothing, etc.), educational/professional lives (rejections by other children, workplace discrimination, absenteeism, etc) and for leisures/sports activities. The patient's economical resources were also heavily impacted by ichthyosis with important out-of-pocket expenses.


Prognostic role of tumor-infiltrating lymphocytes in gastric cancer: A systematic review and meta-analysis.
The potential prognostic value of tumor-infiltrating lymphocytes (TILs) in gastric cancer remains controversial. This meta-analysis examines the association between TILs and survival outcomes in gastric cancer. Twenty-two eligible studies were identified using the PubMed and Google Scholar databases. The combined sample size of the 22 studies was 2941, and the median sample size of the individual studies was 122 patients (52-220). The main clinical outcomes examined were overall cancer survival (OCS) and overall cancer relapse-free survival (OCRFS). Tumor tissue CD3(+) TILs, indicative of pan-T-cell expression, had a positive effect on survival with a hazard ratio (HR) of 0.64 (95% confidence interval [CI] 0.52-0.78) for OCS, as did the non-FOXP3(+) T-cell subgroup with an HR of 0.66 (95% CI 0.57-0.75), particularly in CD8(+) lymphocytes (HR = 0.63, 95% CI 0.48-0.83). On the contrary, high FOXP3(+) T-cell expression was correlated with reduced OCS, with an HR of 1.75 (95% CI 1.26-2.42). Analysis of the seven studies evaluating OCRFS revealed improved OCRFS with infiltration of non-FOXP3(+) TILs with an HR of 0.59 (95% CI 0.42-0.81) but not FOXP3(+) T lymphocytes with an HR of 1.82 (95% CI 1.30-2.53). The results from this meta-analysis suggest that high expression of TILs, mainly by CD8 lymphocytes, may be a potential prognostic biomarker in patients with gastric cancer.


Characterisation of the pharmacokinetics of the fentanyl HCl patient-controlled transdermal system (PCTS): effect of current magnitude and multiple-day dosing and comparison with IV fentanyl administration.
The fentanyl HCl patient-controlled transdermal system (PCTS) is a self-contained, preprogrammed, noninvasive analgesic delivery system for acute pain management. We carried out three studies with the following objectives: study I to evaluate the relationship between fentanyl absorption and the magnitude of current applied to the system; study II to determine dose-proportionality for the fentanyl HCl PCTS (25 and 40 microg); and study III to describe the effects of single- and multiple-day administration on the pharmacokinetics of fentanyl delivered by the PCTS. All studies were open-label, crossover studies with washout periods between treatments. In study I, randomised participants (n = 36) received three of a potential five fentanyl HCl PCTS prototypes, each of which used a different current magnitude, and each of which was evaluated for 24 hours. In study II, participants (n = 40) received fentanyl (25 microg) from the PCTS for 23.33 hours, followed by fentanyl (40 microg) from the PCTS for 23.33 hours. Intravenous (IV) fentanyl (80 microg/h) was administered intermittently over 24 hours as a reference treatment in Studies I and II. In study III, participants (n = 28) received fentanyl (40 microg) from the PCTS for 20 hours, followed by fentanyl (40 microg) from the PCTS for 68 hours. Pharmacokinetic parameters, including maximum serum fentanyl concentration (Cmax), time to Cmax (tmax), area under the serum concentration-time curve (AUC) and terminal half-life (t(1/2)), were determined for each treatment. The amount of fentanyl absorbed from the PCTS was linearly dependent on the magnitude of current applied to the system, with a current of 170 microA resulting in the absorption of 39.5 microg of fentanyl at hour 23. Mixed-effect ANOVA indicated no significant difference (p > 0.1) in the dose-normalised pharmacokinetics of the fentanyl HCl PCTS 25 and 40 microg. No significant difference existed between the corrected AUC(0-5) of the fentanyl HCl PCTS during the single- and multiple-day treatment periods (0.40 and 0.54 microg x h/L, respectively; p = 0.133). The system was well tolerated, with headache and mild application site erythema being the most common treatment-related adverse events. A linear relationship exists between the amount of current applied to the fentanyl HCl PCTS and the amount of fentanyl absorbed. There is dose-proportionality in the pharmacokinetics of the fentanyl HCl PCTS 25 and 40 microg. Multiple-day administration does not affect the pharmacokinetics of the fentanyl HCl PCTS 40 microg. The system was well tolerated, even after repeated application.


Microcontact printing of choline oxidase using a polycation-functionalized zwitterionic polymer as enzyme immobilization matrix.
Highly sensitive and selective choline microbiosensors were constructed by microcontact printing (μCP) of choline oxidase (ChOx) in a crosslinked, polyamine-functionalized zwitterionic polymer matrix on microelectrode arrays (MEAs). μCP has emerged as a potential means to create implantable, multiplexed sensor microprobes, which requires the targeted deposition of different sensor materials to specific microelectrode sites on a MEA. However, the less than sufficient enzyme loading and inadequate spatial resolution achieved with current μCP approaches has limited adoption of the method for electroenzymatic microsensors. A novel polymer, poly(2-methacryloyloxyethyl phosphorylcholine)-g-poly(allylamine hydrochloride) (PMPC-g-PAH), has been developed to address this challenge. PMPC-g-PAH contributes to a higher viscosity "ink" that enables thicker immobilized ChOx deposits of high spatial resolution while also providing a hydrophilic, biocompatible microenvironment for the enzyme. Electroenzymatic choline microbiosensors with sensitivity of 639 ± 96 nA μM-1 cm-2 (pH 7.4; n = 4) were constructed that also are selective against both ascorbic acid and dopamine, which are potential electroactive interfering compounds in the mammalian brain. The high sensitivities achieved can lead to smaller MEA microprobes that minimize tissue damage and make possible the monitoring of multiple neurochemicals simultaneously in vivo with high spatial resolution.


Sex steroids and neurogenesis.
The brain has long been known as a dimorphic organ and as a target of sex steroids. It is also a site for their synthesis. Sex steroids in numerous ways can modify cerebral physiology, and along with many processes adult neurogenesis is also modulated by sex steroids. This review will focus on the effects of the main steroids, estrogens, androgens and progestogens, and unveil some aspects of their partly disclosed mechanisms of actions. Gonadal steroids act on different steps of neurogenesis: cell proliferation seems to be increased by estrogens only, while androgens and progestogens favor neuronal renewal by increasing cell survival; differentiation is a common target. Aging is characterized by a cognitive deficiency, paralleled by a decrease in the rate of neuronal renewal and in the levels of circulating gonadal hormones. Therefore, the effects of gonadal hormones on the aging brain are important to consider. The review will also be expanded to related molecules which are agonists to the nuclear receptors. Sex steroids can modify adult neuronal renewal and the extensive knowledge of their actions on neurogenesis is essential, as it can be a leading pathway to therapeutic perspectives.


Robust statistical methods: A primer for clinical psychology and experimental psychopathology researchers.
This paper reviews and offers tutorials on robust statistical methods relevant to clinical and experimental psychopathology researchers. We review the assumptions of one of the most commonly applied models in this journal (the general linear model, GLM) and the effects of violating them. We then present evidence that psychological data are more likely than not to violate these assumptions. Next, we overview some methods for correcting for violations of model assumptions. The final part of the paper presents 8 tutorials of robust statistical methods using R that cover a range of variants of the GLM (t-tests, ANOVA, multiple regression, multilevel models, latent growth models). We conclude with recommendations that set the expectations for what methods researchers submitting to the journal should apply and what they should report.


Highly Precise Laser-Induced Breakdown Spectroscopy Analysis of Major Mineral Nutrients in Edible Salts Using Miniaturized Salt Ponds and Alternating Laser-Ablation Data Sampling.
In this work, we applied a hydrophilicity-enhanced solid substrate and an alternating laser-ablation data sampling (ALADS) scheme to improve laser-induced breakdown spectroscopy (LIBS) measurement precision and demonstrated the performance in analyzing K, Mg, Ca, and S contained in commercially available edible salt products. Five edible salt products from Australia, Bolivia, France, and South Korea were dissolved in water and a tiny volume of each solution was dropped on the solid substrate, that is, a miniaturized salt pond. After being dried, the residual salt crystals distributed still inhomogeneously, but the homogeneity could be significantly improved in comparison with that from typical drop-and-dry methods. The ALADS scheme was applied to extract three precise measurements from 9798 single-shot LIBS spectra covering the entire salt pond. The measurements obtained by ALADS were found to agree well with one another regardless of the inhomogeneous distribution of salt crystals. As a result, the measurement precision was proved remarkably. Limits of detection for K, Mg, Ca, and S were estimated to be 0.64, 1.7, 14, and 530 mg/kg, respectively, which are enough to analyze those elements contained in salts typically at the level of 100 parts per million (ppm) to ∼3 wt% for the purpose of salt quality assessment.


Structure of aspartoacylase, the brain enzyme impaired in Canavan disease.
Aspartoacylase catalyzes hydrolysis of N-acetyl-l-aspartate to aspartate and acetate in the vertebrate brain. Deficiency in this activity leads to spongiform degeneration of the white matter of the brain and is the established cause of Canavan disease, a fatal progressive leukodystrophy affecting young children. We present crystal structures of recombinant human and rat aspartoacylase refined to 2.8- and 1.8-A resolution, respectively. The structures revealed that the N-terminal domain of aspartoacylase adopts a protein fold similar to that of zinc-dependent hydrolases related to carboxypeptidases A. The catalytic site of aspartoacylase shows close structural similarity to those of carboxypeptidases despite only 10-13% sequence identity between these proteins. About 100 C-terminal residues of aspartoacylase form a globular domain with a two-stranded beta-sheet linker that wraps around the N-terminal domain. The long channel leading to the active site is formed by the interface of the N- and C-terminal domains. The C-terminal domain is positioned in a way that prevents productive binding of polypeptides in the active site. The structures revealed that residues 158-164 may undergo a conformational change that results in opening and partial closing of the channel entrance. We hypothesize that the catalytic mechanism of aspartoacylase is closely analogous to that of carboxypeptidases. We identify residues involved in zinc coordination, and propose which residues may be involved in substrate binding and catalysis. The structures also provide a structural framework necessary for understanding the deleterious effects of many missense mutations of human aspartoacylase.


Behavioural effects of cathinone, an amine obtained from Catha edulis Forsk.: comparisons with amphetamine, norpseudoephedrine, apomorphine and nomifensine.
The effect of khat (Catha edulis Forsk., family Celastraceae), a plant used for its stimulant effects in eastern Africa and southern Arabia, has until recently been attributed to the pharmacological action of d-norpseudoephedrine, also known as cathine. The isolation in 1975 of cathinone revived an earlier suggestion that the fresh leaves contained a substance more potent than cathine. The pharmacological assays reported on in this paper appear to confirm the higher stimulant capacity of cathinone. This substance produces qualitatively similar locomotor stimulation in mice and comparable stereotypy in rats as amphetamine does, although it is approximately half as active. The results obtained after pre-treatment with reserpine or alpha-methyl-p-tyrosine, which interfere with the catecholamine system, strongly suggest that cathinone interacts with brain catecholamines by an indirect mechanism and, most probably, by affecting neurotransmitter release of the labile pool.


Extreme climatic event drives range contraction of a habitat-forming species.
Species distributions have shifted in response to global warming in all major ecosystems on the Earth. Despite cogent evidence for these changes, the underlying mechanisms are poorly understood and currently imply gradual shifts. Yet there is an increasing appreciation of the role of discrete events in driving ecological change. We show how a marine heat wave (HW) eliminated a prominent habitat-forming seaweed, Scytothalia dorycarpa, at its warm distribution limit, causing a range contraction of approximately 100 km (approx. 5% of its global distribution). Seawater temperatures during the HW exceeded the seaweed's physiological threshold and caused extirpation of marginal populations, which are unlikely to recover owing to life-history traits and oceanographic processes. Scytothalia dorycarpa is an important canopy-forming seaweed in temperate Australia, and loss of the species at its range edge has caused structural changes at the community level and is likely to have ecosystem-level implications. We show that extreme warming events, which are increasing in magnitude and frequency, can force step-wise changes in species distributions in marine ecosystems. As such, return times of these events have major implications for projections of species distributions and ecosystem structure, which have typically been based on gradual warming trends.


Classical ethylene insensitive mutants of the Arabidopsis EIN2 orthologue lack the expected 'hypernodulation' response in Lotus japonicus.
Three independent ethylene insensitive mutants were selected from an EMS- mutagenized population of Lotus japonicus MG-20 (Miyakojima). The mutants, called 'Enigma', were mutated in the LjEIN2a gene from Lotus chromosome 1, sharing significant homology with Arabidopsis EIN2 (ethylene-insensitive2). All three alleles showed classical ethylene insensitivity phenotypes (e.g., Triple Response), but lacked the increased nodulation phenotype commonly associated with ethylene insensitivity. Indeed, all showed a marginal reduction in nodule number per plant, a phenotype that is enigmatic to sickle, an ethylene-insensitive EIN2 mutant in Medicago truncatula. In contrast to wild type, but similar to an ETR1-1 ethylene ethylene-insensitive transgenic of L. japonicus, enigma mutants formed nodules in between the protoxylem poles, demonstrating the influence of ethylene on radial positioning. Suppression of nodule numbers by nitrate and colonisation by mycorrhizal fungi in the enigma-1 mutant were indistinguishable from the wild-type MG-20. However, reflecting endogenous ethylene feedback, the enigma-1 mutant released more than twice the wild-type amount of ethylene. enigma-1 had a moderate reduction in growth, greater root mass (and lateral root formation), delayed flowering and ripening, smaller pods and seeds. Expression analysis of ethylene-regulated genes, such as ETR1, NRL1 (neverripe-like 1), and EIL3 in shoots and roots of enigma-1 and MG-20 illustrated that the ethylene-insensitive mutation strongly affected transcriptional responses in the root. These mutants open the possibility that EIN2 in L. japonicus, a determinate nodulating legume, acts in a more complex fashion possibly through the presence of a duplicated copy of LjEIN2.


Recombinant Bet v 1 vaccine for treatment of allergy to birch pollen.
Therapeutic vaccination is the only disease modifying allergy treatment. Recombinant allergen vaccines represent defined component vaccines and are advantageous compared to allergen extract vaccines because of their well defined and measurable allergen content. As the major birch pollen allergen Bet v 1 is the dominant disease-eliciting allergen in birch pollen Bet v 1 vaccines based on GMP produced recombinant (r)Bet v 1 have been developed for treatment of birch pollen allergic patients. Three vaccines comprising hypoallergenic rBet v 1 derivatives have in clinical trials been shown to improve allergic symptoms and to favourable modify the immune response to Bet v 1. In a phase II trial, vaccination with rBet v 1 resulted in reduced rhinoconjunctivitis symptoms and rescue medication compared to placebo. Vaccination with rBet v 1 formulated as tablets for sublingual administration revealed clinical relevant efficacy in rhinoconjunctivitis patients. The positive results imply that rBet v 1 vaccines constitute a therapeutic alternative for birch pollen allergic patients.


The natural history of intravenous catheter-associated phlebitis.
During a controlled evaluation of an intravenous therapy (IVT) team, we had the opportunity to follow up 202 episodes of catheter-associated phlebitis. While the IVT team had a considerable effect on the incidence of phlebitis, the clinical course of this complication was not influenced. More than 40% of catheter-associated phlebitis occurred more than 24 hours after withdrawal of the catheter. Premonitory symptoms were not useful in predicting the development of phlebitis. Factors that influenced the duration of phlebitis included the patient's diagnosis and the administration of vancomycin hydrochloride. The duration of phlebitis was prolonged by delayed removal of the catheter after the development of phlebitis.


Integration within a transgender social network and its effect upon members' social and political activity.
The purpose of this study is to examine the male to female transgender social networks and how they influence social and political activity. Four Transgender organizations within Northeast Ohio were contacted for this study. Members were asked to complete a questionnaire and to mail it back. Few of the network elements were useful in predicting social and political activity. Network size has a positive effect upon a person's social and political activity, as did meeting attendance. This study suggests the importance of social networks for Trans-people.


Temporal changes in population structure of a marine planktonic diatom.
A prevailing question in phytoplankton research addresses changes of genetic diversity in the face of huge population sizes and apparently unlimited dispersal capabilities. We investigated population genetic structure of the pennate planktonic marine diatom Pseudo-nitzschia multistriata at the LTER station MareChiara in the Gulf of Naples (Italy) over four consecutive years and explored possible changes over seasons and from year to year. A total of 525 strains were genotyped using seven microsatellite markers, for a genotypic diversity of 75.05%, comparable to that found in other Pseudo-nitzschia species. Evidence from Bayesian clustering analysis (BA) identified two genetically distinct clusters, here interpreted as populations, and several strains that could not be assigned with ≥ 90% probability to either population, here interpreted as putative hybrids. Principal Component Analysis (PCA) recovered these two clusters in distinct clouds with most of the putative hybrids located in-between. Relative proportions of the two populations and the putative hybrids remained similar within years, but changed radically between 2008 and 2009 and between 2010 and 2011, when the 2008-population apparently became the dominant one again. Strains from the two populations are inter-fertile, and so is their offspring. Inclusion of genotypes of parental strains and their offspring shows that the majority of the latter could not be assigned to any of the two parental populations. Therefore, field strains classified by BA as the putative hybrids could be biological hybrids. We hypothesize that P. multistriata population dynamics in the Gulf of Naples follows a meta-population-like model, including establishment of populations by cell inocula at the beginning of each growth season and remixing and dispersal governed by moving and mildly turbulent water masses.


Comparison of Posttransplant Dermatologic Diseases by Race.
The risk for skin cancer has been well characterized in white organ transplant recipients (OTRs); however, most patients on the waiting list for organ transplant in the United States are nonwhite. Little is known about cutaneous disease and skin cancer risk in this OTR population. To compare the incidence of cutaneous disease between white and nonwhite OTRs. This retrospective review of medical records included 412 OTRs treated from November 1, 2011, through April 22, 2016, at an academic referral center. Prevalence and characteristics of cutaneous disease were compared in 154 white and 258 nonwhite (ie, Asian, Hispanic, and black) OTRs. Clinical factors of cutaneous disease and other common diagnoses assessed in OTRs included demographic characteristics, frequency and type of cancer, anatomical location, time course, sun exposure, risk awareness, and preventive behavior. Primary diagnosis of malignant or premalignant, infectious, and inflammatory disease. The 412 patients undergoing analysis included 264 men (64.1%) and 148 women (35.9%), with a mean age of 60.1 years (range, 32.1-94.3 years). White OTRs more commonly had malignant disease at their first visit (82 [67.8%]), whereas nonwhite OTRs presented more commonly with infectious (63 [37.5%]) and inflammatory (82 [48.8%]) conditions. Skin cancer was diagnosed in 64 (41.6%) white OTRs and 15 (5.8%) nonwhite OTRs. Most lesions in white (294 of 370 [79.5%]) and Asian (5 of 6 [83.3%]) OTRs occurred in sun-exposed areas. Among black OTRs, 6 of 9 lesions (66.7%) occurred in sun-protected areas, specifically the genitals. Fewer nonwhite than white OTRs reported having regular dermatologic examinations (5 [11.4%] vs 8 [36.4%]) and knowing the signs of skin cancer (11 [25.0%] vs 10 [45.4%]). Early treatment of nonwhite OTRs should focus on inflammatory and infectious diseases. Sun protection should continue to be emphasized in white, Asian, and Hispanic OTRs. Black OTRs should be counseled to recognize the signs of genital human papillomavirus infection. Optimal posttransplant dermatologic care may be determined based on the race or ethnicity of the patients, but a baseline full-skin assessment should be performed in all patients. All nonwhite OTRs should be counseled more effectively on the signs of skin cancer, with focused discussion points contingent on skin type and race or ethnicity.


Species-identification of dermatophytes Trichophyton, Microsporum and Epidermophyton by PCR and PCR-RFLP targeting of the DNA topoisomerase II genes.
We have focused on the DNA topoisomerase II genes of pathogenic fungi and have previously applied polymerase chain reaction (PCR)-based identification of several species including the some of the major dermatophyte species. To identify the dermatophytes (18 species) to a species level by PCR and PCR-restriction fragment length polymorphism (RFLP) techniques, without determining the nucleotide sequence. The genomic DNAs of the dermatophytes (ten species of Trichophyton, seven species of Microsporum, and Epidermaphyton floccosum) were amplified by PCR using a common primer set (dPsD1) for the dermatophytes, followed by nested PCR using other primer sets (dPsD2, PsT and PsME) that contained primers specific for the DNA topoisomerase II genes of the dermatophytes. PCRs using PsT and PsME were used for the species-identification of Trichophyton, Microsporum and E. floccosum. The PCR products generated by dPsD2 were digested with restriction enzymes (Hinc II, Hinf, Afl II and PflM I), and the restriction profiles were analyzed. Of the eighteen species of dermatophytes, five species (T. rubrum, T. violaceum, M. canis, M. gypseum and E. floccosum) were specifically identified by the PCR using PsT and PsME to the species level, and the remaining species were identified by the unique restriction profiles for each species in the PCR-RFLP analysis, except that the restriction profile of T. mentagrophytes var. interdigitale was identical to that of T. mentagrophytes var. quinckeanum. PCR and PCR-RFLP techniques targeting the DNA topoisomerase II gene are simple and rapid, and quite useful as tools for the identification of dermatophytes to the species level.


[Experience in long-term use of allapinin in polyclinical practice].
The authors summed up the practical experience gained in long-term maintenance treatment with allapinine, a new Soviet antiarrhythmic agent, given to 65 patients with various cardiac arrhythmias in the outpatient setting. The long-term allapinine use yielded good results: its efficacy was proved to be approximately equal (63% and 60%) in patients with ventricular or supraventricular extrasystoles, respectively, but it was 77% in those with paroxysmal atrial fibrillation. There were no decreases in antiarrhythmic activity of allapinine during its long-term therapy. The agent produced no significant effects on heart rate, blood pressure, and myocardial contractility. Its side effects were recorded in 17 (26.2%) patients, however, withdrawal of the agent was required only in 6 cases.


The etiology and management of diarrhea in the gynecologic oncology patient.
We determined the etiology and evaluated the usefulness of diagnostic tests in 42 gynecologic oncology patients with diarrhea. All inpatients who developed diarrhea during treatment for gynecologic cancer were prospectively evaluated during the 12-month study period ending June 1992. Diarrhea was defined as five or more loose stools per 24 hr lasting for 48 hr or more. Diagnostic tests were complete blood cell count; electrolytes; stool for occult blood, white blood cells, and Clostridia difficile toxin; and stool culture for Shigella, Salmonella, Yersinia, and Campylobacter. During the study period 351 women with gynecologic cancer received inpatient care. Forty-two (12%) patients developed diarrhea. One patient had three episodes and another had two episodes of diarrhea. There were 39 evaluable patients; 3 patients were excluded due to incomplete tests. The only cause of bacterial-associated diarrhea was C. difficile, which occurred in 4 of 39 (10.3%) patients. No patient had community-acquired diarrhea, and 1 patient had diarrhea due to Crohn's Disease. Surgery was performed on 265 patients; 29 of 265 (10.9%) developed postoperative diarrhea. Eighty-six patients had medical treatment and 13 (15.1%) developed diarrhea. The distribution by admission status of patients with diarrhea did not differ statistically from the patients without diarrhea. The four patients with C. difficile-associated diarrhea received appropriate therapy at the time of diagnosis. Nevertheless, the mean (SD) duration of C. difficile-associated diarrhea (342 (103) hr) was significantly longer than the mean (SD) duration of diarrhea not associated with this pathogen (79 (32) hr). The difference between the sample means is 263 hr with a 95% confidence interval for the difference between the means of 218 and 308 hr. Electrolyte abnormalities occurred in 20 patients (51%). Fecal leukocytes were present in 11 (28%) patients and occult blood in 5 (12.8%) of the 39 patients. Neither study was predictive for the presence of C. difficile. Hospital-acquired diarrhea in gynecologic oncology patients is common, although specific bacterial pathogens requiring antibiotic therapy account for only 10% of cases. Diagnostic tests for infectious causes besides C. difficile are infrequently useful and may be omitted unless the condition persists more than 72 hr.


[Hematologic changes in patients under long-term hemodialysis and hemofiltration treatment with special reference to serum concentrations of folic acid and vitamin B 12].
The incidence of macrocytic anemia has been investigated in 32 patients on maintenance hemodialysis (mean age 46 years, mean duration of dialysis treatment 27.5 months), in 18 patients with combined hemodialysis (HD) and hemofiltration (HF) treatment (mean age 42 years, mean duration of combined HD and HF treatment 6.3 months) and in 32 patients after renal transplantation (mean age 41 years, mean observation period since successful renal transplantation 55.2 months). Also investigated were serum levels of vitamin B12 (radioassay kit 57Co) and folic acid (radioassay kit 125J). Macrocytosis (MCV greater than 96 fl) was observed in 38% of the patients on maintenance hemodialysis, in 44% of the patients with combined HD and HF treatment, and in 47% of the renal transplant recipients. In the chronically dialysed patients, in contrast to the patients with combined HD and HF treatment, the mean serum folic acid level was significantly lower (p less than 0.005) than that of healthy controls. Serum levels of vitamin B12 were within the normal range in all patients. There were no significant differences in serum levels of folic acid and vitamin B12 between the patients with MCV greater than 96 fl and MCV less than or equal to 96 fl. Nor was there a correlation between the serum levels of folic acid or vitamin B12 and mean corpuscular volume. These results suggest that folic acid deficiency is of minor importance in the complex pathogenesis of anemia in hemodialysed patients.


Combination of Potassium Pentagamavunon-0 and Doxorubicin Induces Apoptosis and Cell Cycle Arrest and Inhibits Metastasis in Breast Cancer Cells.
A salt compound of a curcumin analogue, potassium pentagamavunon-0 (K PGV-0) has been synthesized to improve solubility of pentagamavunon-0 which has been proven to have anti-proliferative effects on several cancer cells. The purpose of this study was to investigate cytotoxic activity and metastasis inhibition by K PGV- 0 alone and in combination with achemotherapeutic agent, doxorubicin (dox), in breast cancer cells. Based on MTT assay analysis, K PGV-0 showed cytotoxic activity in T47D and 4T1 cell lines with IC50 values of 94.9 μM and 49.0±0.2 μM, respectively. In general, K PGV-0+dox demonstrated synergistic effects and decreased cell viability up to 84.7% in T47D cells and 62.6% in 4T1 cells. Cell cycle modulation and apoptosis induction were examined by flow cytometry. K PGV-0 and K PGV-0+dox caused cell accumulation in G2/M phase and apoptosis induction. Regarding cancer metastasis, while K PGV-0 alone did not show any inhibition of 4T1 cell migration, K PGV-0+dox exerted inhibition. K PGV-0 and its combination with dox inhibited the activity of MMP-9 which has a pivotal role in extracellular matrix degradation. These results show that a combination of K PGV-0 and doxorubicin inhibits cancer cell growth through cell cycling, apoptosis induction, and inhibition of cell migration and MMP-9 activity. Therefore, K PGV-0 may have potential for development as a co-chemotherapeutic agent.


Advances in the use of mass spectral libraries for forensic toxicology.
Gas chromatography in combination with mass spectrometry (GC-MS) plays an important role in the field of analytical toxicology. The identification of unknown compounds is very frequently undertaken with GC-MS and utilizing mass spectral libraries. Currently available libraries for analytical toxicology were compared for overlapping and uniqueness of their entries. Furthermore, the widely known Pfleger-Maurer-Weber-Drugs-and-Pesticides-Library for toxicology (PMW_tox2) was used to compare the search algorithms PBM (Probability Based Matching, Agilent Technologies), INCOS (Finnigan/Thermoquest), and MassLib (Max Planck Institute). To our knowledge, direct comparisons of mass spectral libraries and search programs for analytical toxicology have not been published previously. The capabilities and necessities of modern MS technology in the field of general unknown analysis are revealed, and some of the potential pitfalls are described.


Synthesis of alpha-GaO(OH) nanorods and their optical properties.
Here, we report the synthesis of uniform alpha-GaO(OH) nanorods on Si substrates at low temperature (200 degrees C) using solvothermal technique. alpha-GaO(OH) uniform nanorods is converted to beta-Ga2O3 after annealing at 900 degrees C under ambient atmosphere. A series of electron microscopy characterizations including scanning electron microscopy (SEM), field emission scanning electron microscopy (FESEM) and high resolution transmission electron microscopy (HRTEM) are used to understand the growth mechanism of alpha-GaO(OH) nanorods formation. This nanostructure emits defect-related strong PL emissions at blue (492 nm) and green (522 nm) regions and the relative intensities of these emissions peaks can be modified by varying the reaction conditions. Similarly, we also observed room temperature cathodoluminescence (CL) and the uniform CL contrast of the nanorods in their CL image indicates a homogeneous defect distribution along the nanorods.


Characterization of the Aerosol-Based Synthesis of Uranium Particles as a Potential Reference Material for Microanalytical Methods.
A process for production of micrometer-sized particles composed of uranium oxide using aerosol spray pyrolysis is characterized with respect to the various production parameters. The aerosol is generated using a vibrating orifice aerosol generator providing monodisperse droplets, which are oxidized in a subsequent heat treatment. The final particles are characterized with microanalytical methods to determine size, shape, internal morphology, and chemical and structural properties in order to assess the suitability of the produced particles as a reference material for microanalytical methods, in particular, for mass spectrometry. It is demonstrated that physicochemical processes during particle formation and the heat treatment to chemically transform particles into an oxide strongly influence the particle shape and the internal morphology. Synchrotron μ-X-ray based techniques combined with μ-Raman spectroscopy have been applied to demonstrate that the obtained microparticles consist of a triuranium octoxide phase. Our studies demonstrate that the process is capable of delivering spherical particles with determined uniform size and elemental as well as chemical composition. The particles therefore represent a suitable base material to fulfill the homogeneity and stability requirements of a reference material for microanalytical methods applied in, for example, international safeguards or nuclear forensics.


Pre- and post-melatonin mitigates the effect of ionizing radiation-induced damage in wheat by modulating the antioxidant machinery.
As an indolamine, melatonin (C13H16N2O2) performs essential roles in the regulation of plant growth and development and ameliorates the harmful effects of abiotic stresses. This study examined two types of melatonin application, pre-sowing (prMel) and application during growth (ptMel), in wheat (Triticum aestivum L.) seedlings exposed to four different doses (100, 200, 300, and 400 Gy) of radioactive cobalt (60Co) gamma rays as dry seeds to investigate their ameliorative effects on ionizing radiation (IR) stress. Peroxidase, catalase, superoxide dismutase, ascorbate peroxidase, glutathione reductase, mono- and dihydroxyperoxidase, and phenylalanine ammonia-lyase activities, and levels of lipid peroxidation, H2O2, and total glutathione (GSH), and phenolic acids (PHAs) in soluble free, ester, glycoside and ester-bound forms were examined in the seedlings. Both melatonin applications were found to increase lipid peroxidation, H2O2, and GSH contents previously reduced by gamma irradiation. The IR treatment-induced increases in enzyme activities were significantly reduced by melatonin applications. The study findings indicated that high doses of IR resulted in significant decreases in the activity and levels of the measured traits. The predominant PHAs in the tissues were vanillic, ferulic, and p-coumaric acids. In addition, ptMel application combined with IR stress lowered the total phenolic acid contents in the soluble forms while increasing those in the cell wall-bound form. In conclusion, the antioxidant system in the seedlings exposed to the different gamma ray doses was regulated by prMel and ptMel applications in such a manner as to alleviate IR stress-induced oxidatives damages in the wheat.


Innovation in medical technology: reading the indicators.
Investment in medical technology innovation has enabled significant advances in patient care. An understanding of the dimensions and measures of innovation is critical in fully assessing the implications of many policy initiatives under debate. This Data Watch presents several indicators of inputs and outputs associated with medical device innovation, including public- and private-sector research and development (R&D) investment, patent activity, product regulatory clearance patterns, and market acceptance trends. Changes in these selected indicators point to a potential shift occurring in both the nature of and the investors in the innovation process.


Drug eluting stents in acute myocardial infarction.
Routine stent-implantation in primary coronary intervention (PCI) for acute myocardial infarction (AMI) has been shown to have a better clinical outcome than balloon angioplasty mainly because of reduction in restenosis rate and reocclusion. Drug eluting stents (DES) have recently been proven to further reduce restenosis and revascularization rate in comparison to bare metal stent (BMS) in elective procedures. Delayed endothelialization of these stents raises concern about a possible increase of thrombotic complications in the setting of AMI. Randomized studies with DES in the treatment of elective patients have shown at 9-12 months follow-up a thrombosis rate of 0-2% comparable to the one of BMS. Sirolimus eluting stents (SES) in AMI have been used in small series of consecutive pts not randomized or in registries with very high successful rate and a stent thrombosis varying between 0 and 4.7%. Paclitaxel eluting stent (PES) have also shown in small series a good immediate performance with a thrombosis rate between 0 and 4.8%. Predictors of acute and subacute stent thrombosis are the same than for BMS: residual dissection, long or overlapping stents, biforcation lesions and discontinuation of antiplatelets treatment. Providing effective mechanical reperfusion with similar results to the current therapeutic standard and decreasing the incidence of late complications, DES appear as an attractive approach for patients admitted with AMI.


Metastatic breast carcinoma presenting with profound hypocalcemia.
Hypocalcemia is a rare complication of malignancy. We present the case of a 30-year-old lady presenting with a grand mal seizure due to profound hypocalcemia. She was subsequently found to be hypoparathyroid and was diagnosed with metastatic breast carcinoma. Treatment with goserelin and exemestane produced a significant reduction in her tumor load and a correction of her hypocalcemia, which was initially refractory to treatment. We believe this to be the first case of metastatic breast carcinoma actually presenting with hypocalcemia and feel that clinicians should be aware of this rare complication.


TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis.
T cell immunoglobulin mucin domain-1 (TIM-1) is a phosphatidylserine (PS) receptor, mediating filovirus entry into cells through interactions with PS on virions. TIM-1 expression has been implicated in Ebola virus (EBOV) pathogenesis; however, it remains unclear whether this is due to TIM-1 serving as a filovirus receptor in vivo or, as others have suggested, TIM-1 induces a cytokine storm elicited by T cell/virion interactions. Here, we use a BSL2 model virus that expresses EBOV glycoprotein to demonstrate the importance of TIM-1 as a virus receptor late during in vivo infection. Infectious, GFP-expressing recombinant vesicular stomatitis virus encoding either full length EBOV glycoprotein (EBOV GP/rVSV) or mucin domain deleted EBOV glycoprotein (EBOV GPΔO/rVSV) was used to assess the role of TIM-1 during in vivo infection. GFP-expressing rVSV encoding its native glycoprotein G (G/rVSV) served as a control. TIM-1-sufficient or TIM-1-deficient BALB/c interferon α/β receptor-/- mice were challenged with these viruses. While G/rVSV caused profound morbidity and mortality in both mouse strains, TIM-1-deficient mice had significantly better survival than TIM-1-expressing mice following EBOV GP/rVSV or EBOV GPΔO/rVSV challenge. EBOV GP/rVSV or EBOV GPΔO/rVSV in spleen of infected animals was high and unaffected by expression of TIM-1. However, infectious virus in serum, liver, kidney and adrenal gland was reduced late in infection in the TIM-1-deficient mice, suggesting that virus entry via this receptor contributes to virus load. Consistent with higher virus loads, proinflammatory chemokines trended higher in organs from infected TIM-1-sufficient mice compared to the TIM-1-deficient mice, but proinflammatory cytokines were more modestly affected. To assess the role of T cells in EBOV GP/rVSV pathogenesis, T cells were depleted in TIM-1-sufficient and -deficient mice and the mice were challenged with virus. Depletion of T cells did not alter the pathogenic consequences of virus infection. Our studies provide evidence that at late times during EBOV GP/rVSV infection, TIM-1 increased virus load and associated mortality, consistent with an important role of this receptor in virus entry. This work suggests that inhibitors which block TIM-1/virus interaction may serve as effective antivirals, reducing virus load at late times during EBOV infection.


Toxicity and efficacy of human leukocyte interferon for treatment of cytomegalovirus pneumonia after marrow transplantation.
Eight recipients of marrow transplants with cytomegalovirus (CMV) pneumonia diagnosed by open lung biopsy were treated with doses of human leukocyte interferon of 2 X 10(4)--6.4 X 10(5) units/kg per day to evaluate its toxicity after marrow transplant and its effectiveness against CMV infection. All eight patients died from pneumonia, and virus was still present in lung tissue from seven patients cultured after death. Interferon doses of less than or equal to 1.6 X 10(5) units/kg per day did not affect the circulating granulocyte count. Patients treated with higher doses had a decrease in circulating granulocyte count, but study of granulocyte-macrophage colony-forming cells in culture showed no evidence of toxicity to granulocyte progenitor cells. The effect on in vitro lymphocyte function was variable. Antibody production was not impaired. Interferon was not effective against established CMV infection. However, there was less hematologic toxicity than was anticipated, and the prophylactic use of interferon after marrow transplant is feasible.


Prediction of many-electron wavefunctions using atomic potentials: Refinements and extensions to transition metals and large systems.
For a given many-electron molecule, it is possible to define a corresponding one-electron Schrödinger equation, using potentials derived from simple atomic densities, whose solution predicts fairly accurate molecular orbitals for single-determinant and multideterminant wavefunctions for the molecule. The energy is not predicted and must be evaluated by calculating Coulomb and exchange interactions over the predicted orbitals. Transferable potentials for first-row atoms and transition metal oxides that can be used without modification in different molecules are reported. For improved accuracy, molecular wavefunctions can be refined by slightly scaling nuclear charges and by introducing potentials optimized for functional groups. The accuracy is further improved by a single diagonalization of the Fock matrix constructed from the predicted orbitals. For a test set of 20 molecules representing different bonding environments, the transferable potentials with scaling give wavefunctions with energies that deviate from exact self-consistent field or configuration interaction energies by less than 0.05 eV and 0.02 eV per bond or valence electron pair, respectively. On diagonalization of the Fock matrix, the corresponding errors are reduced by a factor of three to less than 0.016 eV and 0.006 eV, respectively. Applications to the ground and excited states of a Ti18O36 nanoparticle and chlorophyll-a are reported.


CYP2C8 polymorphism frequencies among Han, Uighur, Hui, and Mongolian Chinese populations.
To determine the allele frequency of three codon-changing variants (CYP2C8*2, CYP2C8*3, and CYP2C8*4) in the Han, Uighur, Hui, and Mongolian Chinese populations, and compare genetic polymorphism differences between the Han and minority Chinese ethnicities. Five hundred seventy four healthy unrelated volunteers from four major nationalities (Han: 136; Uighur: 153; Hui: 158; Mongolian: 127) in China were recruited. The study was approved by the local research ethics committee. DNA was extracted from peripheral leukocytes using a standard protocol. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was developed to detect three alleles of CYP2C8. PCR results were confirmed by subsequent direct DNA sequencing. The three minorities showed the CYP2C8 polymorphism with an allele frequency as follows: the allele frequencies of CYP2C8*2, CYP2C8*3, and CYP2C8*4 were 0.33%, 2.94%, and 2.29% in Uighur; 0.39%, 1.57%, and 1.18% in Mongolian, and 0%, 1.58%, and 0.63% in Hui, respectively. For Han, CYP2C8*2, CYP2C8*3, and CYP2C8*4 were absent. To the best of our knowledge, the current study described polymorphisms of CYP2C8 in Chinese minorities for the first time. The results showed that there were significant ethnic differences in the distribution of CYP2C8 in the Han and three minorities, that is, the Uighur, Hui, and Mongolian Chinese populations.


Analysis of chemical characteristics of lignite upgrading wastewater and its agricultural utilization.
The lignite upgrading wastewater (LUW) produced in the drying and upgrading process of lignite cannot be discharged directly. Conventional wastewater treatment methods are usually costly and unable to achieve efficient utilization of water resources which are rich in activity components. In this study, the water quality analysis showed that LUW belonged to seriously polluted waters with low pH and very high total nitrogen content. Fifty-five compounds, mainly phenols and organic acids, were identified by gas chromatography-mass spectrometry (GC-MS) analysis. The study confirmed that the LUW, after being diluted to an appropriate concentration, could significantly promote the growth of wheat seedlings. The phenols and organic acids were the activity material basis of LUW, which promoted seed germination possibly through playing a role similar to plant hormones and simultaneously enhancing the utilization of nutrient elements. LUW had the natural advantages of directly developing high-end liquid fertilizers in terms of its physical form, chemical composition, biological activity, safety and economy. This study confirmed the feasibility of applying LUW to agricultural field as liquid fertilizer only through simple dilution without other treatments. Applying LUW as liquid fertilizer can not only supply a fertilizer product with low production cost and outstanding efficacy, but also provide an efficient and green way for the treatment of upgrading wastewater, which utilize the LUW as natural resources instead of purifying and discharging.


Concurrent gastro-oesophageal intussusception, trichobezoar and hiatal hernia in a cat.
An adult male Birman cat was evaluated for recurrent, intermittent vomiting or regurgitation, occasionally associated with abdominal discomfort. Radiographs, including an oesophogram, indicated an oesophageal obstruction. Prior to treatment, the cat's condition deteriorated and it was euthanised at the owner's request. Post-mortem examination revealed a gastro-oesophageal intussusception, a trichobezoar impacted into the intussusceptum, and a dilated oesophageal hiatus consistent with a chronic hiatal hernia. Gastro-oesophageal intussusception is a rare condition in cats. Its aetiology in relation to a pre-existing hiatal hernia and a trichobezoar is discussed.


The Evaluation of Risk Factors for Postoperative Infectious Complications after Percutaneous Nephrolithotomy.
This study was to evaluate the risk factors of infectious complications after percutaneous nephrolithotomy (PCNL) and build a prediction tool for postoperative complications based on the risk factors. A total of 110 male (67.1%) and 54 female (32.9%) patients who underwent PCNL for renal stones between 2010 and 2014 in our institute were included. A detailed clinical information and laboratory results were obtained from patients. Systemic inflammatory response syndrome (SIRS) and postoperative fever were recorded after PCNL surgery. In all, 45 cases (27.4%) developed SIRS and fever was observed in 20 cases (12.2%). In multivariate analysis, stone size (odds ratio, OR = 1.471, p = 0.009) and urine white blood cell (WBC) (OR = 1.001, p = 0.007) were related to the development of SIRS. Stone size (OR = 1.644, p = 0.024), urine WBC (OR = 1.001, p = 0.002) and serum albumin (OR = 0.807, p = 0.021) were associated with postoperative fever. We concluded that patients with larger stone size and preoperative urinary tract infection might have a higher risk of developing SIRS and fever after operation, while a high-normal level of serum albumin might be the protective factor for postoperative fever.


Mechanisms of embryonic coronary artery development.
Coronary artery development is a complex vasculogenic process that begins shortly after heart looping. Coronary vasculogenesis is regulated by the myocardium, but is spatially and temporally dependent on the epicardium and its precursor, the proepicardial organ, for the provision of coronary vascular progenitor cells. Better understanding of the mechanisms of coronary artery development may clarify mechanisms of disease and suggest new potential therapies for disorders of the coronary vasculature.


FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1134 patients from two prospective cohorts.
Single nucleotide polymorphisms (SNPs) in FCγ-receptor genes FCGR3A (rs396991) and FCGR2A (rs1801274) influence the affinity of the Fc portion of anti-CD20 immunoglobulin G1 monoclonal antibody. Their roles in diffuse large B-cell lymphoma (DLBCL) treated with rituximab in combination with anthracycline-based chemotherapy remain controversial. To address this question, we genotyped FCGR2A and FCGR3A SNPs in two prospective DLBCL cohorts from Lymphoma Study Association trials (N = 554) and Iowa/Mayo Specialized Program Of Research Excellence (N = 580). Correlations with treatment response and hematological toxicity were assessed in Lymphoma Study Association. Correlation with event-free survival (EFS) and overall survival (OS) was performed in both cohorts, followed by a meta-analysis to increase power. Our study shows the absence of correlation between these SNPs and treatment response. Grades 3 and 4 febrile neutropenia during treatment was more frequently observed in FCGR3A VV (39%) than VF (29%) and FF (32%) carriers (p = 0.04). Our analysis for EFS and OS shows that FCGR3A was not associated with outcome. In a meta-analysis using an ordinal model, FCGR2A (per R allele) was associated with a better EFS (hazard ratio = 0.87; 95%CI, 0.76-0.99; p = 0.04) and OS (hazard ratio = 0.86; 95%CI, 0.73-1.00; p = 0.05) which was not altered after adjustment for the International Prognostic Index. Overall, our data demonstrate that patients with DLBCL with the low-affinity FCγRIIA RR had an unexpectedly better outcome than FCγRIIA H carriers. Whether rituximab efficacy is improved in FCγRIIA RR patients due a clearance reduction or other functions of FCγRIIA in DLBCL should be investigated (clinicaltrials.gov identifiers: NCT00135499, NTC00135499 NCT00140595, NCT00144807, NCT00144755, NCT01087424, and NCT00301821). Copyright © 2016 John Wiley & Sons, Ltd.


First record of a Xenophyophore (Rhizaria: Foraminifera) on the Chilean margin.
Xenophyophores are a group of large foraminifera, confined to deep-sea habitats below ~500 m, whose often fragile agglutinated tests may attain sizes up to 10-15 cm or more; their agglutinated tests incorporate a variety of foreign particles (termed 'xenophyae'), including mineral particles, foraminiferan and radiolarian tests, diatom frustules and sponge spicules, and form structures ranging from simple tubes, plates and rounded lumps to complex folded, branching or reticulated formations (Tendal, 1972). Xenophyophores are widely distributed around the world, particularly in the Pacific and Atlantic Oceans with comparatively few records from the Indian Ocean and from Arctic and Antarctic seas; they occur at all depths in the oceans from ~500 m to >10,900 m (Tendal, 1972, 1996) and are particularly abundant in regions of high surface production, for example beneath upwelling zones, or on seamounts and sloped topography where particle flux is high (Levin and Gooday, 1992). There are scant records regarding xenophyophores in the SE Pacific. Species of the order Stannomida are recorded from the Ecuador and Peru margins (north of ~12°S) (Tendal 1972: Figs 18, 19), while species of the order Psamminida are common in the DISCOL experimental area of the Peru Basin (~7° 4'S, 88° 28'W; ~4150 m depth). Maybury and Evans (1994) illustrated two specimens of an undescribed Psammina species collected during the 1989 DISCOL campaign, but otherwise these collections remain largely unpublished.


Using electronic coherence to probe a deeply embedded quantum well in bimetallic Pb/Ag films on Si(111).
We report an experiment in which we utilize electronic coherence to probe a deeply embedded thin film as a quantum well. An atomically uniform Ag film prepared on Si(111) was covered by Pb films up to 70 A thick, and the resulting electronic structure was examined by angle-resolved photoemission spectroscopy. Despite a photoemission escape depth of just a few Angströms and an incommensurate Pb/Ag interface, the data reveal a striking Fabry-Pérot-like structure characteristic of an Ag etalon buried deeply under the Pb overlayers. Our simulations clearly illustrate the manifest coherence of the electronic structures, permitting the characterization of the embedded Ag quantum well.