An alternative approach for management of delayed suprachoroidal hemorrhage after glaucoma procedures.
To introduce an alternative approach for management of delayed suprachoroidal hemorrhage (DSCH) after intraocular procedures, and to report the outcomes of such intervention in a consecutive series of patients. This interventional case series reports consecutive cases of DSCH after glaucoma procedures, managed with a different approach. Instead of the usual 7 to 14 days observation period for clot lysis, the hemorrhage was drained from the suprachoroidal space immediately after diagnosis. Outcome measures included visual acuity and intraocular pressure. Seven eyes of 7 patients including 4 men and 3 women, with mean age of 42.6±29.6 years with DSCH were enrolled. Immediately after the diagnosis, choroidal tap and anterior chamber reformation were performed for all patients and followed for 21.4±13.4 months. Intraocular pressure decreased significantly after intervention (P=0.01). The mean final visual acuity improved significantly to 1.09±0.31 logarithm of minimum angle of resolution (LogMAR) (P=0.003). It seems that surgical drainage immediately after the diagnosis of DSCH can be considered as an alternative to the more conservative approach.


Accuracy and Precision of a Surgical Navigation System: Effect of Camera and Patient Tracker Position and Number of Active Markers.
Surgical navigation systems are increasingly used to aid resection and reconstruction of osseous malignancies. In the process of implementing image-based surgical navigation systems, there are numerous opportunities for error that may impact surgical outcome. This study aimed to examine modifiable sources of error in an idealized scenario, when using a bidirectional infrared surgical navigation system. Accuracy and precision were assessed using a computerized-numerical-controlled (CNC) machined grid with known distances between indentations while varying: 1) the distance from the grid to the navigation camera (range 150 to 247cm), 2) the distance from the grid to the patient tracker device (range 20 to 40cm), and 3) whether the minimum or maximum number of bidirectional infrared markers were actively functioning. For each scenario, distances between grid points were measured at 10-mm increments between 10 and 120mm, with twelve measurements made at each distance. The accuracy outcome was the root mean square (RMS) error between the navigation system distance and the actual grid distance. To assess precision, four indentations were recorded six times for each scenario while also varying the angle of the navigation system pointer. The outcome for precision testing was the standard deviation of the distance between each measured point to the mean three-dimensional coordinate of the six points for each cluster. Univariate and multiple linear regression revealed that as the distance from the navigation camera to the grid increased, the RMS error increased (p<0.001). The RMS error also increased when not all infrared markers were actively tracking (p=0.03), and as the measured distance increased (p<0.001). In a multivariate model, these factors accounted for 58% of the overall variance in the RMS error. Standard deviations in repeated measures also increased when not all infrared markers were active (p<0.001), and as the distance between navigation camera and physical space increased (p=0.005). Location of the patient tracker did not affect accuracy (0.36) or precision (p=0.97). In our model laboratory test environment, the infrared bidirectional navigation system was more accurate and precise when the distance from the navigation camera to the physical (working) space was minimized and all bidirectional markers were active. These findings may require alterations in operating room setup and software changes to improve the performance of this system.


Ovary-independent estrogen receptor expression in neonatal porcine endometrium.
Effects of age and ovariectomy (OVX) at birth on uterine growth, endometrial development, and estrogen receptor (ER) expression were determined for intact and OVX gilts (n = 5 per day) hysterectomized on postnatal days (PND) 0, 15, 30, 60, 90, or 120. Uteri were evaluated histologically, and ER protein and mRNA expression were characterized immunohistochemically and by in situ hybridization. OVX did not affect uterine weight or endometrial thickness until after PND 60, when both increased more rapidly in intact gilts. Neither did it affect genesis of uterine glands, which were present and which proliferated after PND 0, or endometrial ER expression patterns in glandular epithelium (GE), luminal epithelium (LE), or stroma (S) between PND 0 and 120. Endometrium was ER negative at birth. On PND 15, the ER signal was strong in GE, weak in S, and effectively absent in LE. Thereafter, although the ER signal remained strong in GE and increased through PND 60 in S, it was not evident consistently until after PND 30 in LE. The data indicate that 1) porcine uterine growth and endometrial morphogenesis are ovary-independent processes before PND 60; 2) uterine gland genesis is associated temporally with development of ER-positive endometrial GE and S; and 3) regulation of endometrial ER expression is ovary independent between PND 0 and 120. The results establish the ER as a marker of GE differentiation and implicate this receptor in mechanisms regulating endometrial morphogenesis in the neonatal pig.


Persistent accumulation of cyclooxygenase-1-expressing microglial cells and macrophages and transient upregulation by endothelium in human brain injury.
Secondary damage after central nervous system (CNS) injury is driven in part by oxidative stress and CNS inflammation and is substantially mediated by cyclooxygenases (COXs). To date, the rapidly inducible COX-2 isoform has been primarily linked to inflammatory processes, whereas expression of COX-1 is confined to physiological functions. The authors report the differential localization of COX-1 in human traumatic brain injury (TBI). Differential cellular COX-1 protein expression profiles were analyzed following TBI in 31 patients and compared with neuropathologically unaltered control brains by using immunohistochemistry. In these patients with TBI, a significant increase of COX-1 protein expression by vessel endothelial and smooth-muscle cells and CD68+ microglia/macrophages was observed to be strictly confined to the lesion. Accumulation of COX-1+ microglia/macrophages in the lesion was already evident 6 hours postinjury, reaching maximal levels after several weeks and remaining elevated at submaximal levels for several months after injury. Furthermore, COX-1+ cell clusters were located in the Virchow-Robin space during the leukocyte infiltration period from Days 4 to 8 after TBI. Double-labeling experiments confirmed coexpression of COX-1 by CD68+ microglia/macrophages. The numbers of COX-1+ vessel endothelial and smooth-muscle cells increased from Day 1, remaining at submaximal levels for months after injury. The prolonged accumulation of COX- 1+ microglia/macrophages that were restricted to perilesional areas affected by the acute inflammatory response points to a role of COX-1 in secondary injury. The authors have identified localized, accumulated COX- I expression as a potential pharmacological target following TBI. Their results challenge the current paradigms of a selective COX-2 role in the postinjury inflammatory response.


Gut Microbiome (Bacteria, Fungi, and Viruses) and HIV Infection: Revealing Novel Treatment Strategies.
Plenty of research on microbial-viral interactions has revealed that some commensal microorganisms in the gut, including bacteria, fungi, and viruses, can resist or promote viral infection, whereas other microorganisms are involved in pathogenicity. Therefore, the balance between commensal microorganisms and human organisms is a key factor for determining infection and disease progression, and commensal microorganisms have become a hot research area in the medical field. In this review, the compositional characteristics of gut microbiota (bacteria, fungi, and viruses) during HIV infection are reviewed and changes in gut microbiota among different HIV-infected populations are described. Furthermore, the latest progress of potential microbial therapeutic methods, including a) probiotics, prebiotics, and synbiotics, b) fecal microbiota transplantation (FMT), c) phage therapy, and d) antifungal strategy, microbial enzyme inhibition, and dietary therapeutics, is analyzed based on gut bacteria, fungi, and viruses in the field of HIV infection. This study aims to provide a useful reference for developing novel strategies for the prevention and treatment of HIV infection based on commensal microorganisms.


Genome-Wide Identification and Functional Analysis of the Calcineurin B-like Protein and Calcineurin B-like Protein-Interacting Protein Kinase Gene Families in Turnip (Brassica rapa var. rapa).
The calcineurin B-like protein (CBL)-CBL-interacting protein kinase (CIPK) complex has been identified as a primary component in calcium sensors that perceives various stress signals. Turnip (Brassica rapa var. rapa) has been widely cultivated in the Qinghai-Tibet Plateau for a century as a food crop of worldwide economic significance. These CBL-CIPK complexes have been demonstrated to play crucial roles in plant response to various environmental stresses. However, no report is available on the genome-wide characterization of these two gene families in turnip. In the present study, 19 and 51 members of the BrrCBL and BrrCIPK genes, respectively, are first identified in turnip and phylogenetically grouped into three and two distinct clusters, respectively. The expansion of these two gene families is mainly attributable to segmental duplication. Moreover, the differences in expression patterns in quantitative real-time PCR, as well as interaction profiles in the yeast two-hybrid assay, suggest the functional divergence of paralog genes during long-term evolution in turnip. Overexpressing and complement lines in Arabidopsis reveal that BrrCBL9.2 improves, but BrrCBL9.1 does not affect, salt tolerance in Arabidopsis. Thus, the expansion of the BrrCBL and BrrCIPK gene families enables the functional differentiation and evolution of some new gene functions of paralog genes. These paralog genes then play prominent roles in turnip's adaptation to the adverse environment of the Qinghai-Tibet Plateau. Overall, the study results contribute to our understanding of the functions of the CBL-CIPK complex and provide basis for selecting appropriate genes for the in-depth functional studies of BrrCBL-BrrCIPK in turnip.


Food item inventory instructional simulation using microcomputers.
The purpose of this study was to teach the management concepts of perpetual and periodic inventory systems to university students through a food item inventory instructional simulation using microcomputers. The objective of the study was to determine the simulation's effectiveness in enhancing students' understanding of inventory systems management. The participants were senior and graduate students enrolled in a foodservice procurement and inventory systems course at Oregon State University, Corvallis. The population consisted of 68 students, with 34 in the experimental group and 34 in the control group. All the participants completed a pretest to measure existing knowledge of inventory management concepts. This was followed by two classroom lectures, each 50 minutes long, on inventory systems management in foodservice facilities. Members of the experimental group participated in using the food item inventory simulation and study guide after attending both classroom lectures. All the participants of the experimental and control groups completed a post-test 3 weeks after the pretest. The difference in post-test adjusted mean scores between the experimental and control groups was significant (p less than or equal to .05) as determined by analysis of covariance. Therefore, the food item inventory instructional simulation using microcomputers was effective in enhancing students' understanding of the management of perpetual and periodic inventory systems.


Effects of vacancy defects on the interfacial shear strength of carbon nanotube reinforced polymer composite.
We investigate the effects of the vacancy defects (i.e., missing atoms) in carbon nanotubes (CNTs) on the interfacial shear strength (ISS) of the CNT-polyethylene composite with the molecular dynamics simulation. In the simulation, the crystalline polyethylene matrix is set up in a hexagonal array with the polymer chains parallel to the CNT axis. Vacancy defects in the CNT are introduced by removing the corresponding atoms from the pristine CNT (i.e., CNT without any defect). Three patterns of vacancy defects with three different sizes are considered. Two types of interfaces, with and without cross-links between the CNT and the matrix are also considered here. Polyethylene chains are used as cross-links between the CNT and the matrix. The Brenner potential is used for the carbon-carbon interaction in the CNT, while the polymer is modeled by a united-atom potential. The nonbonded van der Waals interaction between the CNT and the polymer matrix and within the polymer matrix itself is modeled with the Lennard-Jones potential. To determine the ISS, we conduct the CNT pull-out from the polymer matrix and the ISS has been estimated with the change of total potential energy of the CNT-polymer system. The simulation results reveal that the vacancy defects significantly influence the ISS. Moreover, the simulation clarifies that CNT breakage occurs during the pull-out process for large size vacancy defect which ultimately reduces the reinforcement.


Identification of novel missense mutations in the Norrie disease gene associated with one X-linked and four sporadic cases of familial exudative vitreoretinopathy.
X-linked Familial Exudative Vitreoretinopathy (XLFEVR) is a hereditary eye disorder that affects both the retina and the vitreous body. It is characterized by an abnormal vascularization of the peripheral retina. It has been previously shown by linkage and candidate gene analysis that XLFEVR and Norrie disease are allelic. In this report we describe four novel mutations (R41K, H42R, K58N, and Y120C) in the Norrie disease gene associated with one X-linked and four sporadic cases of FEVR. One mutation (H42R) was found to be segregating with the disease in three generations (X-linked family), and the others are sporadic. These sequence alterations changed the encoded amino acids in the Norrie disease protein and were not found in 17 unaffected family members or in 36 randomly selected normal individuals. This study provides additional evidence that mutations in the same gene can result in FEVR and Norrie disease. It also demonstrates that it may be beneficial for clinical diagnosis to screen for mutations in the Norrie disease gene in sporadic FEVR cases.


Diagnosis of gastritis by means of a combination of serological analyses.
Gastroscopy and examination of biopsy is normally required for diagnosis of gastritis. This is costly and inconvenient for the patient, and there is a need for a simple pregastroscopic screening method to reduce the endoscopy workload. Our aim was to develop a serological screening test for gastritis. Sera from subjects examined with gastroscopy and biopsy were analyzed for H,K-ATPase antibodies, Helicobacter pylori antibodies and pepsinogen I. The diagnoses were normal gastric mucosa (n=50), duodenal ulcer (n=53) and atrophic corpus gastritis, with (n=50) or without pernicious anemia (n=46). An evaluation scheme was constructed to optimize the diagnostic agreement between serology and gastric mucosal morphology. The sensitivity to detect gastritis was 98% (146/149) (95% CI 94-100%) and the specificity 84% (42/50) (95% CI 71-93%). Additional sera from 483 subjects from the general population were analyzed. There was a good agreement between serology and gastric mucosal morphology. Assays of multiple serum analytes are useful for the initial screening of gastritis. They are complementary to upper gastroscopy by identification of subjects with a normal gastric mucosa, those who qualify for eradication of H. pylori, and those who have developed atrophy and are at risk of developing malignancy and, therefore, require gastroscopic examination.


Ultrastructure of cutaneous granulomas and mononuclear cells from patients with sarcoidosis.
Routine electron microscopy was carried out on biopsy material taken in an active stage from cutaneous sarcoid granulomas of 5 patients. In addition, mononuclear cells isolated from the peripheral blood of 2 patients and 2 controls were studied prior to and after culture with phytohemagglutinin. The infiltrating cells of the sarcoid granulomas varied only slightly from patient to patient. The dominant cell types were macrophages and epithelioid cells rich in endoplasmic reticulum. Epithelioid cells with numerous secondary lysosomes were frequently seen. Typical as well as atypical lymphocytes, giant cells and epithelioid cells with many primary lysosomes were less frequent. No atypical lymphocytes were seen among the mononuclear cells from the peripheral blood, either before or after culture with phytohemagglutinin.


Small scale in vitro method to determine a bioequivalent equilibrium solubility range for fasted human intestinal fluid.
Drug solubility is a key parameter controlling oral absorption, but intestinal solubility is difficult to assess in vitro. Human intestinal fluid (HIF) aspirates can be applied but they are variable, difficult to obtain and expensive. Simulated intestinal fluids (SIF) are a useful surrogate but multiple recipes are available and the optimum is unknown. A recent study characterised fasted HIF aspirates using a multi-dimensional approach and determined nine bioequivalent SIF media recipes that represented over ninety percent of HIF compositional variability. In this study these recipes have been applied to determine the equilibrium solubility of twelve drugs (naproxen, indomethacin, phenytoin, piroxicam, aprepitant, carvedilol, zafirlukast, tadalafil, fenofibrate, griseofulvin, felodipine, probucol) previously investigated using a statistical design of experiment (DoE) approach. The bioequivalent solubility measurements are statistically equivalent to the previous DoE, enclose literature solubility values in both fasted HIF and SIF, and the solubility range is less than the previous DoE. These results indicate that the system is measuring the same solubility space as literature systems with the lower overall range suggesting improved equivalence to in vivo solubility, when compared to DoEs. Three drugs (phenytoin, tadalafil and griseofulvin) display a comparatively narrow solubility range, a behaviour that is consistent with previous studies and related to the drugs' molecular structure and properties. This solubility behaviour would not be evident with single point solubility measurements. The solubility results can be analysed using a custom DoE to determine the most statistically significant factor within the media influencing solubility. This approach has a lower statistical resolution than a formal DoE and is not appropriate if determination of media factor significance for solubilisation is required. This study demonstrates that it is possible to assess the fasted intestinal equilibrium solubility envelope using a small number of bioequivalent media recipes obtained from a multi-dimensional analysis of fasted HIF. The derivation of the nine bioequivalent SIF media coupled with the lower measured solubility range indicate that the solubility results are more likely to reflect the fasted intestinal solubility envelope than previous DoE studies and highlight that intestinal solubility is a range and not a single value.


Interferon-Regulatory Factor 5-Dependent Signaling Restricts Orthobunyavirus Dissemination to the Central Nervous System.
Interferon (IFN)-regulatory factor 5 (IRF-5) is a transcription factor that induces inflammatory responses after engagement and signaling by pattern recognition receptors. To define the role of IRF-5 during bunyavirus infection, we evaluated Oropouche virus (OROV) and La Crosse virus (LACV) pathogenesis and immune responses in primary cells and in mice with gene deletions in Irf3, Irf5, and Irf7 or in Irf5 alone. Deletion of Irf3, Irf5, and Irf7 together resulted in uncontrolled viral replication in the liver and spleen, hypercytokinemia, extensive liver injury, and an early-death phenotype. Remarkably, deletion of Irf5 alone resulted in meningoencephalitis and death on a more protracted timeline, 1 to 2 weeks after initial OROV or LACV infection. The clinical signs in OROV-infected Irf5(-/-) mice were associated with abundant viral antigen and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in several regions of the brain. Circulating dendritic cell (DC) subsets in Irf5(-/-) mice had higher levels of OROV RNA in vivo yet produced lower levels of type I IFN than wild-type (WT) cells. This result was supported by data obtained in vitro, since a deficiency of IRF-5 resulted in enhanced OROV infection and diminished type I IFN production in bone marrow-derived DCs. Collectively, these results indicate a key role for IRF-5 in modulating the host antiviral response in peripheral organs that controls bunyavirus neuroinvasion in mice. Oropouche virus (OROV) and La Crosse virus (LACV) are orthobunyaviruses that are transmitted by insects and cause meningitis and encephalitis in subsets of individuals in the Americas. Recently, we demonstrated that components of the type I interferon (IFN) induction pathway, particularly the regulatory transcription factors IRF-3 and IRF-7, have key protective roles during OROV infection. However, the lethality in Irf3(-/-) Irf7(-/-) (DKO) mice infected with OROV was not as rapid or complete as observed in Ifnar(-/-) mice, indicating that other transcriptional factors associated with an IFN response contribute to antiviral immunity against OROV. Here, we evaluated bunyavirus replication, tissue tropism, and cytokine production in primary cells and mice lacking IRF-5. We demonstrate an important role for IRF-5 in preventing neuroinvasion and the ensuing encephalitis caused by OROV and LACV.


Surgical management of intestinal obstruction after treatment for cancer. Case reports.
Eighty-five consecutive patients operated on for malignant intestinal obstruction after earlier treatment of cancer were studied retrospectively. The overall postoperative mortality was 22% (19/85) and morbidity 42% (36/85). Intra-abdominal sepsis (N = 5) and intestinal fistula (N = 3) were the most common complications, and seven deaths were attributed primarily to the underlying malignant disease. Emergency procedures (p less than 0.003) and age greater than 70 years (p less than 0.025) were significantly associated with fatal outcome. Just over half of the patients were relieved of their symptoms. The median survival was 8 months for the 25 patients who underwent resection and 2 months for the 60 patients for whom no resection was made. The cumulative 5-year survival was significantly better for patients who underwent resection than for those who did not (p less than 0.01) and in patients with regional cancers compared with those with distant growths (p less than 0.001). We conclude that operative treatment for malignant intestinal obstruction is indicated if widespread carcinomatosis and extensive tumour growth are excluded and that this surgery should be done urgently while there is still time to resuscitate the patient.


Total phenolic content, ferric reducing and DPPH scavenging activity of Arum dioscoridis.
Arum dioscoridis, locally called 'Gavur pancari', is a wild plant the leaves of which have been used as vegetable and for preparing special soup which has a sour taste. This study was set up to determine in vitro antioxidant activities and total phenolic and flavonoid contents of different extracts of A. dioscoridis. Free radical scavenging activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing activity with different concentrations of ethanol, methanol, acetone and water extracts of the plant leaves. Total phenolic and flavonoid contents were widely variable depending on solvents. Ethanol and methanol extractions of the plant material showed better performances with respect to both phenolic and flavonoid contents, respectively. The highest phenolic and flavonoid contents of ethanol and methanol extracts were 100.890 mg/g GAE and 72.643 mg/g QE, respectively. The lower DPPH scavenging and ferric reducing activities were determined in comparison with previous reports and standard synthetic chemicals.


Investigation of antibiotic resistance in the genomic era of multidrug-resistant Gram-negative bacilli, especially Enterobacteriaceae, Pseudomonas and Acinetobacter.
The increase and spread of multidrug-resistant (MDR) Gram-negative bacteria, including Enterobacteriaceae, Pseudomonas and Acinetobacter species, have become major concerns worldwide. Although the frequent misuse of antibiotic drugs has greatly contributed to worldwide antibiotic resistance by causing a large dispersal of resistance determinants, recent studies demonstrate that these resistance determinants could have emerged from ancient or environmental sources. Moreover, during the last 10 years, we have been witnessing the emergence and development of technologies for high-throughput sequencing, coinciding with an exponential increase in the number of bacterial genomes sequenced. These sequencing technologies allow a complete study of MDR bacterial genomes and are the best way to investigate the genetic determinants of antimicrobial resistance. Accordingly, studies using genome sequencing to decipher resistance determinants in Enterobacteriaceae, Pseudomonas and Acinetobacter species have demonstrated several advantages including, among others: an exhaustive identification of resistance determinants from any clinical, epidemiological or environmental MDR bacterium; identification of the acquisition mechanisms for resistance determinants exchanged between bacterial species through mobile genetic elements and elucidation and understanding, in record time (less than 1 week), of some critical or epidemic events caused by particular pathogenic bacteria. Therefore, it is clear today that the bacterial genome sequencing approach has revolutionized all fields of scientific research and represents a powerful tool to explore the world of microorganisms.


Brain neurotransmitter receptor alterations in offspring of rats exposed to phenobarbital, phenytoin or their combination during pregnancy.
Neurotransmitter receptor binding was studied in the progeny of rats exposed to phenobarbital (80 mg/kg), phenytoin (80 mg/kg) or their combination daily from 5 to 20 days of gestation. At 22 days postnatally, female pups in all treated groups showed decreased binding of [3H]spiroperidol to striatal membranes. A decreased binding of [3H]diazepam to frontal cortical membranes was observed in the female pups of rats exposed to phenytoin or the combination. The Scatchard analysis of data from the affected groups revealed a decrease in the maximum number of dopamine and benzodiazepine receptor sites and no change in their affinities. The binding of [3H]spiroperidol or [3H]diazepam was not altered significantly in any of the drug-treated male pups. Also, no significant change in the binding of [3H]serotonin or [3H]quinuclidinyl benzilate to frontal cortical membranes was observed in any of the treated groups. At 60 days postnatally, no significant change in the binding of any of the above ligands was evident. The above prenatal drug exposures appear to cause transitory subsensitivity of dopamine and benzodiazepine receptors in rats.


An innovative application of time-domain spectroscopy on localized surface plasmon resonance sensing.
White-light scanning interferometry (WLSI) is often used to study the surface profiles and properties of thin films because the strength of the technique lies in its ability to provide fast and high resolution measurements. An innovative attempt is made in this paper to apply WLSI as a time-domain spectroscopic system for localized surface plasmon resonance (LSPR) sensing. A WLSI-based spectrometer is constructed with a breadboard of WLSI in combination with a spectral centroid algorithm for noise reduction and performance improvement. Experimentally, the WLSI-based spectrometer exhibits a limit of detection (LOD) of 1.2 × 10-3 refractive index units (RIU), which is better than that obtained with a conventional UV-Vis spectrometer, by resolving the LSPR peak shift. Finally, the bio-applicability of the proposed spectrometer was investigated using the rs242557 tau gene, an Alzheimer's and Parkinson's disease biomarker. The LOD was calculated as 15 pM. These results demonstrate that the proposed WLSI-based spectrometer could become a sensitive time-domain spectroscopic biosensing platform.


Guided-Mode-Leaky-Mode-Guided-Mode Fiber Interferometer and Its High Sensitivity Refractive Index Sensing Technology.
A cascaded symmetrical dual-taper Mach-Zehnder interferometer structure based on guided-mode and leaky-mode interference is proposed in this paper. Firstly, the interference spectrum characteristics of interferometer has been analyzed by the Finite Difference-Beam Propagation Method (FD-BPM). When the diameter of taper waist is 20 μm-30 μm, dual-taper length is 1 mm and taper distance is 4 cm-6 cm, the spectral contrast is higher, which is suitable for sensing. Secondly, experimental research on refractive index sensitivity is carried out. A refractive index sensitivity of 62.78 nm/RIU (refractive index unit) can achieved in the RI range of 1.3333-1.3792 (0%~25% NaCl solution), when the sensor structure parameters meet the following conditions: diameter of taper waist is 24 μm, dual-taper length is 837 μm and taper distance is 5.5 cm. The spectrum contrast is 0.8 and measurement resolution is 1.6 × 10(-5) RIU. The simulation analysis is highly consistent with experimental results. Research shows that the sensor has promising application in low RI fields where high-precision measurement is required due to its high sensitivity and stability.


High-degree and broad-spectrum resistance mediated by a combination of NIb siRNA and miRNA suppresses replication of necrotic and common strains of potato virus Y.
In plants, viral replication can be inhibited through gene silencing, which is mediated by short interfering RNA (siRNA) or microRNA (miRNA). However, under natural conditions, viruses are extremely susceptible to mutations that may decrease the efficiency of cleavage of these small RNAs (sRNAs). Therefore, a single sRNA may not provide a sufficient degree of viral resistance to transgenic plants. Potato virus Y necrotic strain (PVYN) and Potato virus Y common strain (PVYO) are the two major PVY strains that cause systemic necrosis and mottling, respectively, in tobacco. In this study, we designed specific siRNAs and miRNAs to target two regions of the PVYO replicase gene (NIb). Eight plant expression vectors containing one or two sRNAs were constructed. Luciferase activity assays showed that the designed sRNAs successfully cleaved the NIb gene of PVYO and PVYN, and the vector carrying a combined siRNA- and miRNA-based short hairpin RNA (shRNA) demonstrated the strongest inhibitory effect. These effects were confirmed through the acquisition of PVYO and PVYN resistance in transgenic sRNA-expressing Nicotiana tabacum plants. This phenomenon could be related to a plant defense mechanism in which siRNA and miRNA pathways are complementary and interact to achieve gene silencing. Furthermore, there is a tendency for the homologous small RNA sequences (PVYO) to be more effective in conferring resistance than those with imperfect homology (PVYN). Overall, these findings confirm that the use of a combined siRNA- and miRNA-based shRNAs is a promising approach for introducing viral resistance to plants through genetic engineering.


Inhibitors of polyamine biosynthesis. 3. (+/-)-5-Amino-2-hydrazine-2-methylpentanoic acid, an inhibitor of ornithine decarboxylase.
(+/-)-5-Amino-2-hydrazino-2-methylpentanoic acid [alpha-hydrazino-alpha-methyl-(+/-)-ornithine] was obtained from 1-phthalimidopentan-4-one by treatment with hydrazine and KCN followed by acid hydrolysis. The title compound was found in vitro to be a potent competitive inhibitor of ornithine decarboxylase obtained from the prostate glands of rats. This inhibition was abolished at high concentrations of pyridoxal phosphate. The title compound also blocked the increase in putrescine levels normally observed in bovine lymphocytes transformed by conconavalin A.


Extraction of a Large Central Airway Foreign Body Using Flexible Bronchoscopy Combined with an Endobronchial Blocker.
Adult foreign body (FB) aspiration is an uncommon but potentially fatal event. Options for extraction include flexible bronchoscopy (FLXB), rigid bronchoscopy (RB), and surgical extraction. We report the case of a large, smooth aspirated rock causing airway obstruction in an elderly male. RB is generally the preferred approach for extraction of a large complex FB; however, due to its size, the FB had to be removed using FLXB combined with an endobronchial blocker. In this report, we describe the anesthetic and surgical considerations and the novel technique used to extract the FB.


A qualitative assessment of barriers to antiretroviral therapy adherence among adolescents in western Kenya.
Antiretroviral therapy (ART) requires nearly perfect adherence to be effective. This study aims to identify key factors identified by HIV-infected adolescents on ART as contributing to medication adherence in western Kenya. Using a qualitative study design, three adolescent focus groups discussions were conducted at an urban and rural clinic site in western Kenya. The study population included HIV-infected adolescents receiving ART through the USAID-AMPATH HIV care system. A trained facilitator conducted groups in Kiswahili using a semi-structured interview guide probing multiple aspects of experience of taking medicines. Transcribed focus group dialogues were analyzed using constant comparison, progressive coding, and triangulation. The adolescents described a context of negative societal beliefs about HIV, necessitating a lifestyle of secrecy and minimizing the information shared about HIV or ART. Assessing and addressing adolescents' fears and behaviors regarding medication secrecy and disclosure may enable more accurate monitoring of adherence and development of intervention strategies.


The burden of generalized anxiety disorder in Canada.
Although generalized anxiety disorder (GAD) is common and disabling, there are few Canadian studies on this mental illness. We compared the characteristics, health status, health services use and health care needs of Canadians with GAD to those with depression. Data are from the 2012 Canadian Community Health Survey-Mental Health, which surveyed a nationally representative sample of Canadians aged 15 years and older (n = 23 709; response rate of 68.9%). The respondents we studied had selfreported symptoms compatible with GAD and/or major depressive episode (MDE) in the preceding 12 months (n = 1598). Estimates were weighted to represent the Canadian household population. We performed descriptive and multinomial multivariate logistic regression analyses. In 2012, an estimated 700 000 (2.5%) Canadians aged 15 years and older reported symptoms compatible with GAD in the previous 12 months. MDE symptoms co-occurred in 50% of these individuals. Those with GAD only reported fair/poor perceived health (29.7%), moderate to severe psychological distress (81.2%) and moderate to severe disability (28.1%) comparable to (or even slightly worse) than those with MDE only (24.7%, 78.8% and 24.8% respectively). Those with comorbid GAD and MDE demonstrated the worst health outcomes; 47.3% of them reported fair/poor perceived health, 94.0% reported moderate to severe psychological distress and 52.4% reported moderate to severe disability. Nearly 50% of those with comorbid GAD and MDE reported that their need for health care was not met or only partially met, compared to about 30% of those with GAD or MDE only. While GAD is associated with levels of distress and disability comparable to (or slightly worse) than those affected by MDE only, the health status of those with comorbid disease is significantly worse than those with GAD or MDE only. Improved diagnosis, screening for comorbidity and management are essential to minimize the impacts of this mental illness.


Microveneering technique for esthetic enhancement of monolithic zirconia restorations.
The importance of monolithic ceramic restorations is growing, given the safe and cost-effective options for fabrication of such dental crowns and fixed dental prostheses. The optical characteristics of traditional zirconia do not suffice for this purpose. Improved restorative materials that can achieve satisfactory results in posterior restorations have been proposed to solve the problem. In the anterior region, however, even "esthetic" zirconia ceramic is unable to attain results comparable to those of glass-ceramic. Microveneering is a simple, reliable, and timesaving solution. Minimal reduction and veneering can significantly improve the results. A characteristic case is presented here.


Matrix attachment regions and regulated transcription increase and stabilize transgene expression.
Transgene silencing has been shown to be associated with strong promoters, but it is not known whether the propensity for silencing is caused by the level of transcription, or some other property of the promoter. If transcriptional activity fosters silencing, then transgenes with inducible promoters may be less susceptible to silencing. To test this idea, a doxycycline-inducible luciferase transgene was transformed into an NT1 tobacco suspension culture cell line that constitutively expressed the tetracycline repressor. The inducible luciferase gene was flanked by tobacco Rb7 matrix attachment regions (MAR) or spacer control sequences in order to test the effects of MARs in conjunction with regulated transcription. Transformed lines were grown under continuous doxycycline (CI), or delayed doxycycline induction (DI) conditions. Delayed induction resulted in higher luciferase expression initially, but continued growth in the presence of doxycycline resulted in a reduction of expression to levels similar to those found in continuously induced lines. In both DI and CI treatments, the Rb7 MAR significantly reduced the percentage of silenced lines and increased transgene expression levels. These data demonstrate that active transcription increases silencing, especially in the absence of the Rb7 MAR. Importantly, the Rb7 MAR lines showed higher expression levels under both CI and DI conditions and avoided silencing that may occur in the absence of active transcription such as what would be expected as a result of condensed chromatin spreading.


SleepSense: A Noncontact and Cost-Effective Sleep Monitoring System.
Quality of sleep is an important indicator of health and well being. Recent developments in the field of in-home sleep monitoring have the potential to enhance a person's sleeping experience and contribute to an overall sense of well being. Existing in-home sleep monitoring devices either fail to provide adequate sleep information or are obtrusive to use. To overcome these obstacles, a noncontact and cost-effective sleep monitoring system, named SleepSense, is proposed for continuous recognition of the sleep status, including on-bed movement, bed exit, and breathing section. SleepSense consists of three parts: a Doppler radar-based sensor, a robust automated radar demodulation module, and a sleep status recognition framework. Herein, several time-domain and frequency-domain features are extracted for the sleep recognition framework. A prototype of SleepSense is presented and evaluated using two sets of experiments. In the short-term controlled experiment, the SleepSense achieves an overall 95.1% accuracy rate in identifying various sleep status. In the 75-minute sleep study, SleepSense demonstrates wide usability in real life. The error rate for breathing rate extraction in this study is only 6.65%. These experimental results indicate that SleepSense is an effective and promising solution for in-home sleep monitoring.


Internal tandem duplication mutations in the tyrosine kinase domain of FLT3 display a higher oncogenic potential than the activation loop D835Y mutation.
Acute myeloid leukemia (AML) remains the most common form of acute leukemia among adults and accounts for a large number of leukemia-related deaths. Mutations in FMS-like tyrosine kinase 3 (FLT3) is one of the most prevalent findings in this heterogeneous disease. The major types of mutations in FLT3 can be categorized as internal tandem duplications (ITD) and point mutations. Recent studies suggest that ITDs not only occur in the juxtamembrane region as originally described, but also in the kinase domain. Although the juxtamembrane ITDs have been well characterized, the tyrosine kinase domain ITDs have not yet been thoroughly studied due to their recent discovery. For this reason, we compared ITD mutations in the juxtamembrane domain with those in the tyrosine kinase domain, as well as with the most common activating point mutation in the tyrosine kinase domain, D835Y. The purpose of this study was to understand whether it is the nature of the mutation or the location of the mutation that plays the main role in leukemogenesis. The various FLT3 mutants were expressed in the murine pro-B cell line Ba/F3 and examined for their capacity to form colonies in semisolid medium. The size and number of colonies formed by Ba/F3 cells expressing either the internal tandem duplication within juxtamembrane domain of the receptor (JMD-ITD) or the tyrosine kinase domain (TKD)-ITD were indistinguishable, while Ba/F3 cells expressing D835Y/FLT3 failed to form colonies. Cell proliferation and cell survival was also significantly higher in TKD-ITD expressing cells, compared to cells expressing D835Y/FLT3. Furthermore, TKD-ITD is capable of inducing phosphorylation of STAT5, while D835Y/FLT3 fails to induce tyrosine phosphorylation of STAT5. Other signal transduction pathways such as the RAS/ERK and the PI3K/AKT pathways were activated to the same level in TKD-ITD cells as compared to D835Y/FLT3 expressing cells. Taken together, our data suggest that TKD-ITD displays similar oncogenic potential to the JMD-ITD but a higher oncogenic potential than the D835Y point mutation.


[The helminth and coccidial fauna of pheasants (Phasianus colchicus) in view of the specific environmental conditions in pheasantries and in the wild].
Between October 1999 and January 2000 all together 151 male pheasants were examined for endoparasites. 33 one-year-old birds came from two pheasantries, the remaining 118 birds, aged between one and five years, were wildlife animals. The infestation extensy of all pheasants with endoparasites were 96.7%. A mostly low infestation with coccidia of the three species Eimeria (E.) phasiani, E. duodenalis and E. tetartooimia were detected in 41% of all birds. E. tetartooimia was found in Germany for the first time. In 67.5% of the pheasants the five different species of capillaria (Capillaria (C.) annulata, C. bursata, C. contorta, C. perforans, C. phasianina) and in 84.1% the nematode Heterakis gallinarum were present. Pheasants in the capture group showed higher infestation intensy and extensy. In 51.5% of the pheasants of the capture group Syngamus trachea was present. In one pheasant an acanthocephalus (Plagiorhynchus cylindraceus) was detected for the first time in Germany and in two pheasants a trematode of the genus Echinostoma was present.


Single-cell enumeration of an uncultivated TM7 subgroup in the human subgingival crevice.
Specific oligonucleotide hybridization conditions were established for single-cell enumeration of uncultivated TM7 and IO25 bacteria by using clones expressing heterologous 16S rRNA. In situ analysis of human subgingival crevice specimens revealed that a greater proportion of samples from sites of chronic periodontitis than from healthy sites contained TM7 subgroup IO25. In addition, IO25 bacterial cells from periodontitis site samples were more abundant and fourfold longer than IO25 cells from healthy site samples.


Interrelationship between hemolysis and lipid peroxidation of human erythrocytes induced by silicic acid and silicate dusts.
Silicic acid and silicate dusts (slate dust and chrysotile asbestos) cause hemolysis of erythrocytes in vitro. The peroxidation of polyunsaturated fatty acids (PUFA) of erythrocyte membrane lipids is also enhanced by incubating the erythrocytes with silicic acid and silicate dusts in in vitro. Hemolysis of erythrocytes elicited by silicic acid and silicate dusts is inhibited significantly by polyvinyl-pyrrolidone and dipalmitoyl lecithin (DPL). These agents, however, have no effect on silicic acid and silicate dust induced peroxidation of erythrocyte membrane lipids. On the other hand, peroxidation of erythrocyte membrane lipids, induced by silicic acid and silicate dusts, is inhibited almost completely by adding superoxide dismutase and catalase to the incubation system, whilst the hemolysis of erythrocytes induced by silicic acid and silicate dusts is unaffected by these agents. Similarly the lysis of erythrocytes, induced by silicic acid and silicate dusts, proceeds at a much faster rate than silicic acid and silicate dust induced lipid peroxidation. These results indicate that silicic acid and silicate dust induced hemolysis and lipid peroxidation represent two independent processes.


Improving Diabetic Retinopathy in an Indigent Population.
Diabetic retinopathy is the leading cause of preventable blindness in working-age American adults. This study hypothesized that patients with diabetes types I and II at St.Luke's Free Medical Clinic in Spartanburg, South Carolina were not being systematically referred for annual diabetic retinopathy screening. We evaluated the number of patients referred for screening, those patients who actually went for the screening, and the rate at which retinopathy was found in those who went. Of the 111 charts reviewed, only 49.5% of the patients were referred to an eye care professional between January 1, 2013 and December 31, 2014. Of those referred, 21.1% were found to have vision-threatening pathology. The median number of days to have an eye exam was 28.5. A standardized method to screen for diabetic retinopathy in the clinic would alleviate the referral burden and ultimately allow for detection of ocular pathology earlier in the course of disease.


Reducing STD and HIV risk behavior of substance-dependent adolescents: a randomized controlled trial.
A randomized controlled trial assessed 3 interventions designed to increase safer sex behaviors of substance-dependent adolescents. Participants (N = 161) received 12 sessions of either a health information intervention (I only), information plus skills-based safer sex training (I + B), or the same experimental condition plus a risk-sensitization manipulation (I + M + B). The I + B and I + M + B conditions, as compared with the I only condition, (a) produced more favorable attitudes toward condoms; (b) reduced the frequency of unprotected vaginal sex; and (c) increased behavioral skill performance, frequency of condom-protected sex, percentage of intercourse occasions that were condom protected, and number of adolescents who abstained from sex. The intervention that included the risk-sensitization procedure was more resistant to decay. An unexpected finding was that the I + B and I + M + B conditions produced substantial increases in sexual abstinence.


Tuning the oxidative power of free iron-sulfur clusters.
The gas-phase reactions between a series of di-iron sulfur clusters Fe2Sx+ (x = 1-3) and the small alkenes C2H4, C3H6, and C4H8 have been investigated by means of Fourier-transform ion-cyclotron resonance mass spectrometry. For all studied alkenes, the reaction efficiency is found to increase in the order Fe2S+ < Fe2S2+ < Fe2S3+. In particular, Fe2S+ and Fe2S2+ only form simple association products, whereas the sulfur-rich Fe2S3+ is able to dehydrogenate propene and 2-butene via desulfurization of the cluster and formation of H2S. This indicates an increased propensity to induce oxidation reactions, i.e. oxidative power, of Fe2S3+ that is attributed to an increased formal oxidation state of the iron atoms. Furthermore, the ability of Fe2S3+ to activate and dissociate the C-H bonds of the alkenes is observed to increase with increasing size of the alkene and thus correlates with the alkene ionization energy.


Evaluation of ovarian toxicity of sodium valproate (VPA) using cultured rat ovarian follicles.
Sodium valproate (VPA) is a major antiepileptic drug that is widely used for the treatment of epilepsy as well as other neuropsychiatric diseases. The present study was conducted to evaluate the ovarian toxicity of VPA using cultured rat ovarian follicles. Secondary follicles were isolated from the ovaries of 14-day-old female rats and cultured for 48 hr with VPA (0, 0.2, 1.0, and 5.0 mM). At 0, 24, and 48 hr of VPA treatment, follicular diameters were measured. After the culture, viability of follicles and expression of aromatase in the follicles were assessed, and progesterone, androstenedione, testosterone, and estradiol levels in culture media were measured. At all concentrations of VPA, follicular development was suppressed, and androstenedione, testosterone, estradiol, and combined levels of all steroid hormones tended to decrease in association with suppression of aromatase expression in granulosa cells. Additionally, the suppression of follicular development was associated with decreased viability of follicles and an increased progesterone level at 5.0 mM of VPA. The decrease in the combined levels of all steroid hormones implies that VPA suppresses the synthetic pathway from cholesterol to estradiol including de novo synthesis of cholesterol. In conclusion, VPA induces ovarian toxicity via suppression of development and abnormal steroid hormone synthesis in cultured rat ovarian follicles.


Photoredox-Based Actuation of an Artificial Molecular Muscle.
The use of light to actuate materials is advantageous because it represents a cost-effective and operationally straightforward way to introduce energy into a stimuli-responsive system. Common strategies for photoinduced actuation of materials typically rely on light irradiation to isomerize azobenzene or spiropyran derivatives, or to induce unidirectional rotation of molecular motors incorporated into a 3D polymer network. Although interest in photoredox catalysis has risen exponentially in the past decade, there are far fewer examples where photoinduced electron transfer (PET) processes are employed to actuate materials. Here, a novel mode of actuation in a series of redox-responsive hydrogels doped with a visible-light-absorbing ruthenium-based photocatalyst is reported. The hydrogels are composed primarily of polyethylene glycol and low molar concentrations of a unimolecular electroactive polyviologen that is activated through a PET mechanism. The rate and degree of contraction of the hydrogels are measured over several hours while irradiating with blue light. Likewise, the change in mechanical properties-determined through oscillatory shear rheology experiments-is assessed as a function of polyviologen concentration. Finally, an artificial molecular muscle is fabricated using the best-performing hydrogel composition, and its ability to perform work, while irradiated, is demonstrated by lifting a small weight.


Combined Infection with Cucumber green mottle mosaic virus and Pythium Species Causes Extensive Collapse in Cucumber Plants.
In the last decade, the phenomenon of late-wilting has increased in cucumber greenhouses during Cucumber green mottle mosaic virus (CGMMV) epidemics. Because the wilting appears in defined patches accompanied by root rot, it was hypothesized that the phenomenon is caused by coinfection of soilborne pathogens and CGMMV. A field survey showed that 69% of the collapsed plants were infected with both Pythium spp. and CGMMV, whereas only 20 and 6.6% were singly infected with Pythium spp. or CGMMV, respectively. Artificial inoculations in controlled-environmental growth chambers and glasshouse experiments showed that coinfection with Pythium spinosum and CGMMV leads to a strong synergistic wilting effect and reduces growth parameters. The synergy values of the wilting effect were not influenced by the time interval between P. spinosum and CGMMV infection. However, dry mass synergy values were decreased with longer intervals between infections. The results obtained in this study support the complexity of the wilting phenomenon described in commercial cucumber grown in protected structures during infection of Pythium spp. on the background of a vast CGMMV epidemic. They encourage a wider perspective of the complexity of agricultural diseases to apply the most suitable disease management.


Cost effectiveness of the two-compound formulation calcipotriol and betamethasone dipropionate gel in the treatment of scalp psoriasis in Scotland.
To compare the cost effectiveness of the two-compound formulation (TCF) calcipotriol plus betamethasone dipropionate gel used first-, second- or third-line to standard topical treatments for moderately severe scalp psoriasis from a Scottish NHS perspective. Treatment pathways for scalp psoriasis patients in primary care were defined by Scottish prescribing statistics, an interview programme and published sources. The extensive 1-year Markov model included 12 different topical treatment pathways, each simulating three lines of therapy. Seven pathways contained the TCF gel in first-, second- or third-line. The remaining five pathways were included as comparators, reflecting the heterogeneity across clinical practice. The cost effectiveness of TCF gel was compared to the average of five non-TCF gel pathways. The clinical effectiveness measure was the ability of topical treatments to control disease at 4 weeks. Response rates were derived from indirect comparisons of ten randomised controlled trials. Utilities were elicited from SF-36 (v2) scores in one TCF gel trial. The main outcome was the incremental cost per quality-adjusted life-year (QALY). Extensive sensitivity analyses were performed to assess the robustness of the results. TCF gel used first-, second- or third-line was projected to increase QALYs (around 0.0025) with cost savings per patient (£20-30) over 1 year. The study analysis acknowledged a number of limitations including lack of quality comparator data, the need to make assumptions in the absence of evidence and lack of model validation. However the results showed that TCF gel was the dominant treatment strategy across a broad range of credible scenarios. Scalp psoriasis is difficult to treat. Many different topical preparations can be used but several factors such as greasiness, irritation, time needed to apply, and lack of efficacy often result in reduced adherence to treatment regimens. Where cosmetic properties are important for patient acceptability and compliance is a major issue contributing to treatment failure, the once-daily TCF gel offers patients with scalp psoriasis an attractive, cost-saving treatment option.


Psychiatry and the resource-based relative value scale.
Attention to reform of reimbursement for psychiatric inpatient services largely focuses on the use of prospective payment systems, e.g., payment based on diagnosis-related groups (DGRs), for hospitals. Recently, there also has been interest in proposals for altering physician reimbursement (inpatient and outpatient) by using physician DRGs, capitation models, or relative value scales instead of the charge-based, fee-for-service model. The authors review the resource-based relative value scale (RBRVS) as an option for psychiatry. The RBRVS uses the setting, the time spent, the difficulty in treating the patient, the training, and the psychiatrist's role to determine reimbursement rates.


Simplified analogues of immucillin-G retain potent human purine nucleoside phosphorylase inhibitory activity.
A set of deazaguanine derivatives 1-3 targeting human purine nucleoside phosphorylase (hPNP) have been designed and synthesized. The new compounds are characterized by the presence of a structurally simplified "azasugar" motif to be more easily accessible by chemical synthesis than previous inhibitors. In the enzymatic assays, some of the new derivatives proved to be able to inhibit hPNP at low nanomolar concentration, thereby showing the same inhibitory potency in vitro as immucillin-H (IMH). Molecular docking experiments revealed a binding mode to hPNP essentially identical to that of IMH. As a result, the lower in vivo activity exhibited by 1d, compared with that exhibited by IMH, might be ascribed to differences in the pharmacokinetic, rather than pharmacodynamic, profile between these compounds. Derivatives 1a, 1d, and 2c emerged as the most active compounds within this new set and may represent interesting leads in the search for novel hPNP inhibitors.


Luteolin Impacts on the DNA Damage Pathway in Oral Squamous Cell Carcinoma.
Oral squamous cell carcinoma (OSCC) exhibited high chemoresistance to current treatments. Here we aimed at identifying and repositioning approved drugs that could be selectively toxic toward OSCC cells. Through a cell-based drug screening of 1,280 chemical molecules, we selected compounds lethal to oral cancer SCC-25 cells, while sparing normal keratinocyte HaCaT cells. Within the chemical library, the natural flavonoid luteolin was identified as a potent cytotoxic agent against oral cancer cells in vitro, along with metixene hydrochloride and nitazoxanide. Of note, they exhibit low toxicity and high efficiency compared to the standard-of-care, such as cisplatin and the epidermal growth factor receptor inhibitor tyrphostin. From a molecular standpoint, luteolin causes phosphorylation of ataxia telangiectasia mutated (ATM) and H2AX in a DNA repair pathway and can be efficiently combined with a checkpoint kinase (CHK) pharmacological inhibitor. Thus, luteolin emerges as a potent cytotoxic and/or adjuvant therapy in oral cancer, as it is a natural compound presenting better effects in vitro compared to conventional chemotherapeutic agents. Future in vivo exploration is next required to provide the proof-of-concept that luteolin could be an efficient anticancer molecule.


Absence of BRAFV600E immunohistochemical expression in sporadic odontogenic keratocyst, syndromic odontogenic keratocyst and orthokeratinized odontogenic cyst.
Odontogenic keratocyst (OKC) is a unique developmental odontogenic cyst that has the potential to behave aggressively and is associated with the nevoid basal cell carcinoma syndrome. Orthokeratinized odontogenic cyst (OOC) is a distinct, uncommon odontogenic cyst. It significantly differs from OKC not only in its epithelial lining but also in proliferating kinetics, clinical, immunohistochemical and biological behaviour. BRAF gene located on chromosome 7q34 encodes a cytoplasmic serine-threonine kinase. Various immunohistochemical studies have been conducted to express the BRAFV600E gene mutation in various odontogenic cyst and tumours with varying results. The present study was conducted to evaluate the possible role of BRAFV600E in the pathogenesis of sporadic OKC, syndromic OKC and OOC by immunohistochemistry. Formalin-fixed paraffin-embedded (FFPE) tissue blocks of 15 diagnosed cases each of sporadic OKC, syndromic OKC and OOC were retrieved from the archives of Department of Oral Pathology and subjected to immunohistochemical staining for the detection of BRAFV600E mutation using a novel rabbit monoclonal antibody clone RM8. Immunohistochemical analysis showed complete absence of BRAFV600E mutation in all cases of sporadic OKC, syndromic OKC and OOC. The negative immunohistochemical expression of BRAFV600E in sporadic OKC, syndromic OKC and OOC suggests that BRAFV600E plays no role in the pathogenesis of sporadic OKC, syndromic OKC and OOC.


Diminished proteinuria in diabetes mellitus by sorbinil, an aldose reductase inhibitor.
Proteinuria was diminished by concomitant oral administration of sorbinil, an aldose reductase inhibitor to streptozotocin-induced diabetic rats. Animals were placed in one of three groups: control, diabetic, sorbinil-treated diabetic. For a period of 10 weeks, 24-hour urine samples were analyzed weekly for volume, glucose, ketone, total protein (Pesce-Strande) and individual protein components having molecular weights between 15,000 and 120,000 daltons. The latter were examined by polyacrylamide gel electrophoresis and quantitated by laser densitometric analysis. Results indicated that controls excreted albumin (68,000 daltons) and low-molecular weight proteins between 15,000 and 20,000 daltons. Throughout the 10-week period of diabetes, there was a 7- to 12-fold increase in total urinary protein excreted in 24 h. Diabetic-induced proteinuria primarily resulted from excretion of newly detected proteins having molecular weights of 30,000-100,000 daltons and an increase amount of albumin. Sorbinil treatment prevented approximately 70% of the increase in total protein excretion despite persistent hyperglycemia, glycosuria and ketonuria. Laser densitometric analysis indicated that the aldose reductase inhibitor decreased by 70% the excretion of newly detected proteins and albumin while maintaining the 15,000- to 20,000-dalton proteins. These results suggest that the polyol pathway is implicated in diabetic-induced proteinuria and inhibition of aldose reductase may represent a therapeutic approach for management of diabetic nephropathy.


Triclinic crystal structure distortion of multiferroic BiMn7O12.
The quadruple perovskite BiMn7O12 obtained via high-pressure synthesis was investigated by high-resolution synchrotron X-ray powder diffraction over a temperature range of 10 to 295 K. Careful Rietveld analysis reveals triclinic lattice distortion of BiMn7O12 at 295 K, which increases upon cooling to 10 K. Also hkl-dependent anisotropic Bragg reflection shape was introduced to give a precise description of the diffracted intensities. Importantly BiMn7O12 crystal structure was described in the non-centrosymmetric I1 triclinic space group. We also demonstrate the use of irreducible representations analysis (ISODISTORT program) for crystal structure distortion from Im to I1 space group. The irreducible representation which describes crystal structure distortion points towards possible ferroelectricity. Finally anisotropic thermal lattice expansion was observed.


A mid-infrared laser microscope for the time-resolved study of light-induced protein conformational changes.
We have developed a confocal laser microscope operating in the mid-infrared range for the study of light-sensitive proteins, such as rhodopsins. The microscope features a co-aligned infrared and visible illumination path for the selective excitation and probing of proteins located in the IR focus only. An external-cavity tunable quantum cascade laser provides a wavelength tuning range (5.80-6.35 µm or 1570-1724 cm-1) suitable for studying protein conformational changes as a function of time delay after visible light excitation with a pulsed LED. Using cryogen-free detectors, the relative changes in the infrared absorption of rhodopsin thin films around 10-4 have been observed with a time resolution down to 30 ms. The measured full-width at half maximum of the Airy disk at λ = 6.08 µm in transmission mode with a confocal arrangement of apertures is 6.6 µm or 1.1λ. Dark-adapted sample replacement at the beginning of each photocycle is then enabled by exchanging the illuminated thin-film location with the microscope mapping stage synchronized to data acquisition and LED excitation and by averaging hundreds of time traces acquired in different nearby locations within a homogeneous film area. We demonstrate that this instrument provides crucial advantages for time-resolved IR studies of rhodopsin thin films with a slow photocycle. Time-resolved studies of inhomogeneous samples may also be possible with the presented instrument.


Sperm DNA damage is associated with assisted reproductive technology pregnancy.
The literature suggests an association between sperm DNA damage and assisted reproductive technology (ART) outcomes. However, previous studies involved the transfer of multiple embryos, which has complicated the interpretation of the results. The aim of this study was to determine the relationship between the levels of sperm DNA damage and fertilization rate, embryo development as well as pregnancy outcome, following single embryo transfer. Patients (n = 113) undergoing in vitro fertilization (IVF) (n = 45) and intra-cytoplasmic sperm injection (ICSI) (n = 68) were assessed for their levels of sperm DNA damage in the sample used for insemination. DNA damage was determined using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labelling (TUNEL). The relationship between DNA damage and outcomes were assessed using regression analysis. Overall data showed no association between sperm DNA damage and fertilization rate, or embryo development in vitro. However, when IVF was the insemination method, there was a significant negative correlation between fertilization rates and sperm DNA damage (p < 0.05). When ICSI was the insemination technique, low sperm DNA damage was associated with successful pregnancy (37.8 +/- 5.7% DNA damaged sperm) compared with failed implantation (52.9 +/- 3.9% DNA damaged sperm, p < 0.05). Our results suggest that sperm DNA damage as measured by the TUNEL assay may provide an indicator for patients with poor fertilization rates and/or those unable to achieve pregnancy following ART treatment.


A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6.
Successive parameterizations of the GROMOS force field have been used successfully to simulate biomolecular systems over a long period of time. The continuing expansion of computational power with time makes it possible to compute ever more properties for an increasing variety of molecular systems with greater precision. This has led to recurrent parameterizations of the GROMOS force field all aimed at achieving better agreement with experimental data. Here we report the results of the latest, extensive reparameterization of the GROMOS force field. In contrast to the parameterization of other biomolecular force fields, this parameterization of the GROMOS force field is based primarily on reproducing the free enthalpies of hydration and apolar solvation for a range of compounds. This approach was chosen because the relative free enthalpy of solvation between polar and apolar environments is a key property in many biomolecular processes of interest, such as protein folding, biomolecular association, membrane formation, and transport over membranes. The newest parameter sets, 53A5 and 53A6, were optimized by first fitting to reproduce the thermodynamic properties of pure liquids of a range of small polar molecules and the solvation free enthalpies of amino acid analogs in cyclohexane (53A5). The partial charges were then adjusted to reproduce the hydration free enthalpies in water (53A6). Both parameter sets are fully documented, and the differences between these and previous parameter sets are discussed.


Resistance mechanisms in an in vitro-selected amoxicillin-resistant strain of Helicobacter pylori.
We investigated the beta-lactam resistance mechanism(s) of an in vitro-selected amoxicillin-resistant Helicobacter pylori strain (AmoxR). Our results demonstrated that resistance is due to a combination of amino acid substitutions in penicillin binding protein 1 (PBP1), HopB, and HopC identified in AmoxR, resulting in decreased affinity of PBP1 for amoxicillin and decreased accumulation of penicillin.


A Description of a Validated Effective Teacher-Training Workshop for Medical Residents.
A teacher-training program for residents was designed and piloted in the St. Elisabeth Hospital in Curaçao, Netherlands Antilles. The program comprised of six modules namely: effective teaching, self-knowledge and teaching ability, feedback, assessing prior knowledge, trouble shooting and time management. Instruction was provided during a two-day workshop with eight hours instruction time per day. Residents in the first three years of training participated, and the instructors were experienced clinicians. Lectures, group discussions, case simulations, video presentations and role-plays were the forms of instruction. Using standardized questionnaires, the participants rated the quality of the workshop highly. They considered it to be a feasible and appropriate educational intervention and that it had a positive impact on their teaching skills. This workshop was developed based on careful analysis of medical residents' perceived educational needs and systematically implemented and evaluated. The results show that it is a suitable and effective educational intervention.


Arousal and drug abuse.
The reticular activating system (RAS) is not an amorphous region but distinct nuclei with specific membrane properties that dictate their firing during waking and sleep. The locus coeruleus and raphe nucleus fire during waking and slow wave sleep, with the pedunculopontine nucleus (PPN) firing during both waking and REM sleep, the states manifesting arousal-related EEG activity. Two important discoveries in the PPN in the last 10 years are, 1) that some PPN cells are electrically coupled, and 2) every PPN cell manifests high threshold calcium channels that allow them to oscillate at beta/gamma band frequencies. The role of arousal in drug abuse is considered here in terms of the effects of drugs of abuse on these two mechanisms. Drug abuse and the perception of withdrawal/relapse are mediated by neurobiological processes that occur only when we are awake, not when we are asleep. These relationships focus on the potential role of arousal, more specifically of RAS electrical coupling and gamma band activity, in the addictive process as well as the relapse to drug use.


Addressing the problem of increased antibiotic resistance.
Growing bacterial resistance to antibiotics is causing grave concern in both community and hospital settings. Mismanagement has been identified as the main cause. The problem can be addressed at ground level by careful use of antibiotics, through meticulous personal and environmental hygiene and preventive infection-control measures.


The level of BMP4 signaling is critical for the regulation of distinct T-box gene expression domains and growth along the dorso-ventral axis of the optic cup.
Polarised gene expression is thought to lead to the graded distribution of signaling molecules providing a patterning mechanism across the embryonic eye. Bone morphogenetic protein 4 (Bmp4) is expressed in the dorsal optic vesicle as it transforms into the optic cup. Bmp4 deletions in human and mouse result in failure of eye development, but little attempt has been made to investigate mammalian targets of BMP4 signaling. In chick, retroviral gene overexpression studies indicate that Bmp4 activates the dorsally expressed Tbx5 gene, which represses ventrally expressed cVax. It is not known whether the Tbx5 related genes, Tbx2 and Tbx3, are BMP4 targets in the mammalian retina and whether BMP4 acts at a distance from its site of expression. Although it is established that Drosophila Dpp (homologue of vertebrate Bmp4) acts as a morphogen, there is little evidence that BMP4 gradients are interpreted to create domains of BMP4 target gene expression in the mouse. Our data show that the level of BMP4 signaling is critical for the regulation of distinct Tbx2, Tbx3, Tbx5 and Vax2 gene expression domains along the dorso-ventral axis of the mouse optic cup. BMP4 signaling gradients were manipulated in whole mouse embryo cultures during optic cup development, by implantation of beads soaked in BMP4, or the BMP antagonist Noggin, to provide a local signaling source. Tbx2, Tbx3 and Tbx5, showed a differential response to alterations in the level of BMP4 along the entire dorso-ventral axis of the optic cup, suggesting that BMP4 acts across a distance. Increased levels of BMP4 caused expansion of Tbx2 and Tbx3, but not Tbx5, into the ventral retina and repression of the ventral marker Vax2. Conversely, Noggin abolished Tbx5 expression but only shifted Tbx2 expression dorsally. Increased levels of BMP4 signaling caused decreased proliferation, reduced retinal volume and altered the shape of the optic cup. Our findings suggest the existence of a dorsal-high, ventral-low BMP4 signaling gradient across which distinct domains of Tbx2, Tbx3, Tbx5 and Vax2 transcription factor gene expression are set up. Furthermore we show that the correct level of BMP4 signaling is critical for normal growth of the mammalian embryonic eye.


Levels of vancomycin in aqueous humor after topical eye drops administration.
Vancomycin is an antibiotic which is especially active against Gram positive bacteria. At present, numerous infections of the anterior segment of the eye are caused by the Staphilococcus aureus and epidermis. Strains which are resistant to methicilin are more and more frequent and for this reason Vancomycin is becoming the antibiotic of choice to combat these infections since no resistance of the Staphilococcus to it has been demonstrated. The authors evaluated the levels of Vancomycin in aqueous humor after the administration of topical eye-drops. For the first two hours after the last administration, levels of 0.52 micrograms/ml were detected. These inhibit the growth of the majority of bacteria sensitive to Vancomycin. Between two and four hours, the levels decreased to 0.15 micrograms/ml; these are therapeutic levels for a large number of Gram positive bacteria. From four hours after the last administration, these levels are undetectable. Due to the success of its penetration, topical administration of Vancomycin should be considered as a therapeutic modality against infections by gram positive bacteria of the anterior segment. The ideal guideline for administration would be one drop every two hours, especially if the infection is severe. In this way, subconjunctival injection could be avoided.


Oncogenic miR-744 promotes prostate cancer growth through direct targeting of LKB1.
Prostate cancer (PCa) is one of the most common malignancies worldwide, and with a limited number of treatments for this type of cancer, its incidence is rapidly increasing. Patients presenting with PCa are likely to experience disease recurrence, which represents a considerable clinical challenge. MicroRNAs (miRNAs) have been widely characterized as a critical regulator in a number of types of cancer, including PCa. miRNA-744 (miR-744) has been reported to be involved in cancer regulation; however, its role in PCa remained poorly understood. In a recent study, it was demonstrated that miR-744 was overexpressed in prostate tissue from PCa patients when compared with the surrounding tissues, and knockdown of miR-744 resulted in reduced cell growth. In addition, an increased population of apoptotic cells was detected upon miR-744 knockdown, together with a decrease in cell proliferation. Cell cycle analysis demonstrated a higher number of cells in the G1 phase and lower numbers in the S phase following miR-744 silencing. The levels of key proteins involved in cell cycle progression (cyclin D1, cyclin-dependent kinase 4, and proliferating cell nuclear antigen) were increased, whereas those proteins responsible for cell cycle inhibition (cyclin-dependent kinase inhibitor p21) were decreased. The tumor suppressor liver kinase B1 (LKB1) was revealed to be a potential target of miR-744, suggesting its potential mechanism of action. LKB1 levels were negatively correlated with miR-744, and LKB1 was indicated to be a direct target of miR-744. Furthermore, it was revealed that by targeting LKB1, miR-744 may regulate adenosine monophosphate-activated protein kinase (AMPK); the AMPK signaling pathway was activated by miR-744 knockdown, with subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway. Taken together, these results demonstrated that miR-744 promoted cell growth through the AMPK signaling pathway, by targeting LKB1. The present study revealed a novel insight into the biological function of miR-744 in PCa, and that miR-744 may be a potential therapeutic target.


Relationship between Pericytes and Endothelial Cells in Retinal Neovascularization: A Histological and Immunofluorescent Study of Retinal Angiogenesis.
To evaluate the relationship between pericytes and endothelial cells in retinal neovascularization through histological and immunofluorescent studies. C57BL/6J mice were exposed to hyperoxia from postnatal day (P) 7 to P12 and were returned to room air at P12 to induce a model of oxygen-induced retinopathy (OIR). The cross sections of enucleated eyes were processed with hematoxylin and eosin. Immunofluorescent staining of pericytes, endothelial cells, and N-cadherin was performed. Microfluidic devices were fabricated out of polydimethylsiloxane using soft lithography and replica molding. Human retinal microvascular endothelial cells, human brain microvascular endothelial cells, human umbilical vein endothelial cells and human placenta pericyte were mixed and co-cultured. Unlike the three-layered vascular plexus found in retinal angiogenesis of a normal mouse, angiogenesis in the OIR model is identified by the neovascular tuft extending into the vitreous. Neovascular tufts and the three-layered vascular plexus were both covered with pericytes in the OIR model. In this pathologic vascularization, N-cadherin, known to be crucial intercellular adhesion molecule, was also present. Further evaluation using the microfluidic in vitro model, successfully developed a microvascular network of endothelial cells covered with pericytes, mimicking normal retinal angiogenesis within 6 days. Pericytes covering endothelial cells were observed not only in vasculature of normal retina but also pathologic neovascularization of OIR mouse at P17. Factors involved in the endothelial cell-pericyte interaction can be evaluated as an attractive novel treatment target. These future studies can be performed using microfluidic systems, which can shorten the study time and provide three-dimensional structural evaluation.


Model-based PSF and MTF estimation and validation from skeletal clinical CT images.
A method was developed to correct for systematic errors in estimating the thickness of thin bones due to image blurring in CT images using bone interfaces to estimate the point-spread-function (PSF). This study validates the accuracy of the PSFs estimated using said method from various clinical CT images featuring cortical bones. Gaussian PSFs, characterized by a different extent in the z (scan) direction than in the x and y directions were obtained using our method from 11 clinical CT scans of a cadaveric craniofacial skeleton. These PSFs were estimated for multiple combinations of scanning parameters and reconstruction methods. The actual PSF for each scan setting was measured using the slanted-slit technique within the image slice plane and the longitudinal axis. The Gaussian PSF and the corresponding modulation transfer function (MTF) are compared against the actual PSF and MTF for validation. The differences (errors) between the actual and estimated full-width half-max (FWHM) of the PSFs were 0.09 ± 0.05 and 0.14 ± 0.11 mm for the xy and z axes, respectively. The overall errors in the predicted frequencies measured at 75%, 50%, 25%, 10%, and 5% MTF levels were 0.06 ± 0.07 and 0.06 ± 0.04 cycles/mm for the xy and z axes, respectively. The accuracy of the estimates was dependent on whether they were reconstructed with a standard kernel (Toshiba's FC68, mean error of 0.06 ± 0.05 mm, MTF mean error 0.02 ± 0.02 cycles/mm) or a high resolution bone kernel (Toshiba's FC81, PSF FWHM error 0.12 ± 0.03 mm, MTF mean error 0.09 ± 0.08 cycles/mm). The method is accurate in 3D for an image reconstructed using a standard reconstruction kernel, which conforms to the Gaussian PSF assumption but less accurate when using a high resolution bone kernel. The method is a practical and self-contained means of estimating the PSF in clinical CT images featuring cortical bones, without the need phantoms or any prior knowledge about the scanner-specific parameters.


Effects of nitrogen fertilizers on the bacterial community diversity and the weathering of purple mudstone in Southwest China.
Rock weathering is crucial in the development of soil. Yet the role of bacteria in the fine particle-forming process of purple mudstone is not fully understood, especially under nitrogen fertilization. In this study, the particles (0.25 mm to 1 mm) of purple mudstone from Penglai Group (J3p) were selected as the test material. Two nitrogen fertilizers, i.e., urea (U) and ammonium bicarbonate (AB), and four application levels (0, 280, 560, and 840 N kg∙ha-1) with 18 replications were designed in an incubation experiment. The weathering indices and bacterial community structure of the purple mudstone particles were investigated after 120 days of incubation. The results showed that the weathering indices of purple mudstone particles in the AB treatment were higher than that in the U treatment at the same fertilization levels and a reducing trend was observed with increasing nitrogen fertilizer levels under the same nitrogen fertilizer application types. The diversities of the bacterial community were extremely significantly altered by nitrogen fertilizer application (p < 0.01). The effect of the nitrogen fertilizer application level on the beta diversity of the bacterial community (R2 = 0.34) was greater than that of the nitrogen fertilizer application type (R2 = 0.20). Through stepwise regression analysis, the positive effects of nitrification of Nitrobacter (Nitrolancea) (R2 = 0.36), the Phosphorous-dissolving bacteria (Massilia) (R2 = 0.12), and N-NO3- (R2 = 0.35) on the weathering indices of J3p purple mudstone particles could be observed. Structural equation modelling indicated that nitrogen fertilizer application level affects the abundance of the dominant species at the genus level (Nitrolancea and Massilia), and key environmental factor (N-NO3-), which in turn accelerated the weathering indices (59%). Our findings imply that the enhancements of nitrification of Nitrobacter (Nitrolancea) and of phosphorus solubilization of Phosphorous-dissolving bacteria (Massilia) by nitrogen fertilization are the key factors affecting the weathering indices of J3p purple mudstone particles.


Post-Babesiosis Warm Autoimmune Hemolytic Anemia.
Background Babesiosis, a tickborne zoonotic disease caused by intraerythrocytic protozoa of the genus babesia, is characterized by nonimmune hemolytic anemia that resolves with antimicrobial treatment and clearance of parasitemia. The development of warm-antibody autoimmune hemolytic anemia (also known as warm autoimmune hemolytic anemia [WAHA]) in patients with babesiosis has not previously been well described. Methods After the observation of sporadic cases of WAHA that occurred after treatment of patients for babesiosis, we conducted a retrospective cohort study of all the patients with babesiosis who were cared for at our center from January 2009 through June 2016. Data on covariates of interest were extracted from the medical records, including any hematologic complications that occurred within 3 months after the diagnosis and treatment of babesiosis. Results A total of 86 patients received a diagnosis of babesiosis during the 7.5-year study period; 18 of these patients were asplenic. WAHA developed in 6 patients 2 to 4 weeks after the diagnosis of babesiosis, by which time all the patients had had clinical and laboratory responses to antimicrobial treatment of babesiosis, including clearance of Babesia microti parasitemia. All 6 patients were asplenic (P<0.001) and had positive direct antiglobulin tests for IgG and complement component 3; warm autoantibodies were identified in all these patients. No alternative explanation for clinical hemolysis was found. WAHA required immunosuppressive treatment in 4 of the 6 patients. Conclusions We documented post-babesiosis WAHA in patients who did not have a history of autoimmunity; asplenic patients appeared to be particularly at risk.


Total alkaloids of Rubus aleaefolius Poir inhibit hepatocellular carcinoma growth in vivo and in vitro via activation of mitochondrial-dependent apoptosis.
The aim of this study was to evaluate the therapeutic efficacy of Rubus aleaefolius Poir total alkaloids (TARAP) against hepatocellular carcinoma growth in vivo and in vitro, and to investigate the possible molecular mechanisms mediating its biological activity. Nude mice were implanted with HepG2 human hepatocellular carcinoma cells and fed with vehicle (physiological saline) or 3 g/kg/d dose of TARAP, 5 days per week, for 21 days. The in vivo efficacy of TARAP against tumor growth was investigated by evaluating its effect on tumor volume and tumor weight in mice with HCC xenografts and its adverse effect was determined by measuring the body weight gain. The in vitro effect of TARAP on the viability of HepG2 cells was determined by MTT assay. HepG2 cell morphology was observed via phase-contrast microscopy. Apoptosis in tumor tissues or in HepG2 cells was analyzed by TUNEL assay or FACS analysis with Annexin V/PI, respectively. The loss of mitochondrial membrane potential in HepG2 cells was determined via JC-1 staining followed by FACS analysis. Activation of caspase-9 and -3 in HepG2 cells was examined by a colorimetric assay. The mRNA and protein expression of Bcl-2 and Bax in tumor tissues were measured by RT-PCR and immunohistochemistry. TARAP reduced tumor volume and tumor weight, but had no effect on the body weight gain in HCC mice. TARAP decreased the viability of HepG2 cells and induced cell morphological changes in vitro in a dose- and time-dependent manner. In addition, TARAP induced apoptosis both in tumor tissues and in HepG2 cells. Moreover, TARAP treatment resulted in the collapse of mitochondrial membrane potential in HepG2 cells, as well as the activation of caspase-9 and -3. Furthermore, administration of TARAP increased the pro-apoptotic Bax/Bcl-2 ratio in HCC mouse tumors, at both transcriptional and translational levels. TARAP inhibits hepatocellular carcinoma growth both in vivo and in vitro probably through the activation of mitochondrial-dependent apoptosis, which may, in part, explain its anticancer activity. These results suggest that total alkaloids in Rubus aleaefolius Poir may be a potential novel therapeutic agent for the treatment of hepatocellular carcinoma and other cancers.


Risk factors for retinopathy of prematurity in extremely preterm Chinese infants.
To investigate the incidence and risk factors of retinopathy of prematurity (ROP) and Type 1 ROP in extremely preterm Chinese infants. A retrospective review of medical records was performed of all extremely preterm neonates (gestational age, GA≤28 weeks) screened for ROP from 2007 to 2012 at an ophthalmology centre in Hong Kong. Thirty-three maternal and neonatal covariates were analyzed using univariate and multivariate regression analyses for both ROP and Type 1 ROP. The mean gestational age (GA) was 26.4±1.3 weeks and the birth weight (BW) was 855.0±199.0 g. The incidence of ROP development was 60.7% and 16.2% for Type 1 ROP. On univariate analysis, 6 risk factors were identified for ROP development including: lighter BW; lower GA; postnatal hypotension; inotrope use; surfactant use; and invasive mechanical ventilation (all P≤0.01). On multivariate analysis, neonatal congenital heart disease and greater GA were protective factors for ROP development (P≤0.04). On the other hand, 4 risk factors were associated with Type 1 ROP development in univariate analysis, including: lower GA, lighter BW, multiple pregnancies, and invasive mechanical ventilation (all P≤0.02); while there was no significant risk factors on multivariate analysis. A lighter BW and lower GA were the only common independent risk factors for both ROP and Type 1 ROP while neonatal congenital heart disease and greater GA were the protective factors against ROP.


Unexpected multiple bond cleavage and rearrangement of organosulfide ligands in the presence of Cu(II) assisted by solvothermal and solvothermal-microwave conditions.
An unprecedented in situ multiple bond cleavage of S-S, S-C(sp(2)) and C-N in the pyrimidinedisulfide (pym(2)S(2)) ligand is observed by the reaction of CuCl(2)·2H(2)O with this ligand under solvothermal and solvothermal-microwave conditions. In this process the formation of the compound [Cu(II)(μ-Cl)(Cl)L](2), where L represents the new ligand (L = 2-(pyrimidin-2-ylamino)-1,3-thiazole-4-carbaldehyde), is observed. This ligand has been further isolated and X-ray characterized. The similar reaction carried out under solvothermal-microwave conditions gives, in addition to the latter compound, the complex {9·[Cu(pym(2)S(3))(μ-Cl)(Cl)](2)·[Cu(pym(2)S(2))(μ-Cl)(Cl)](2)}. Coordination of a pyrimidinetrisulfide ligand (pym(2)S(3)) is reported for the first time. This work represents an illustrative example of the novel synthetic perspectives attainable via solvothermal-microwave procedures.


Hepatitis E virus infections in travellers: assessing the threat to the Australian blood supply.
In many developed countries hepatitis E virus (HEV) infections have occurred predominantly in travellers to countries endemic for HEV. HEV is a potential threat to blood safety as the virus is transfusion-transmissible. To minimise this risk in Australia, individuals diagnosed with HEV are deferred. Malarialdeferrals, when donors are restricted from donating fresh blood components following travel toanareain which malaria is endemic, probably also decrease the HEV risk, by deferring donors who travel to many countries also endemic for HEV. The aim of this study is to describe overseas-acquired HEV cases in Australia, in order to determine whether infection in travellers poses a risk to Australian blood safety. Details of all notified HEV cases in Australia from 2002 to 2014 were accessed, and importation rates estimated. Countries in which HEV was acquired were compared to those for which donations are restricted following travel because of a malaria risk. Three hundred and thirty-two cases of HEV were acquired overseas. Travel to India accounted for most of these infections, although the importation rate was highest for Nepal and Bangladesh. Countries for which donations are restricted following travel due to malaria risk accounted for 94% of overseas-acquired HEV cases. The vast majority of overseas-acquired HEV infections were in travellers returning from South Asian countries, which are subject to donation-related travel restrictions for malaria. This minimises the risk HEV poses to the Australian blood supply.


Estradiol acts locally within the retrochiasmatic area to inhibit pulsatile luteinizing-hormone release in the female sheep during anestrus.
In the present study we have identified a site of action of estradiol in the inhibition of LH secretion during anestrus in the ewe. In the first experiment, we studied six sites: the medial preoptic area, the lateral preoptic area, the ventromedial hypothalamus, the ventrolateral hypothalamus, the retrochiasmatic area (RCh), and the periventricular posterior hypothalamus. We compared the changes in parameters of pulsatile LH secretion (interpulse interval, mean nadir, mean amplitude, and mean area under curve) during three 6-h sampling periods: before and 30-36 h and 9 days after intracerebral implantation of crystalline estradiol. Animals that received estradiol in the RCh (n = 5) showed a significantly greater increase in both the intervals between pulses of LH (up 116%, p < 0.03) and the area under the curve (up 180%, p < 0.01) than any of the other groups of 7 animals. In the second experiment, implantation of estradiol in the RCh (n = 6) induced an increase in the intervals between pulses of LH (p < 0.03), whereas receiving an empty implant (n = 6) had no effect, showing that estradiol specifically induced increases in the intervals between pulses. Thus, estradiol appears to act in the RCh where the dopaminergic A15 nucleus, known to inhibit pulsatile LH release, is located.


Artefactual low lymphocyte activity caused by platelet contamination in the mononuclear cell preparations.
Platelet (PLT) contamination in preparations of mononuclear cells (MNC) produces a significant decrease (P less than 0.02) in lymphoproliferative activity and interleukin 2 (IL2) production. This effect was observed in MNC preparations from either healthy blood donors or polyglobulic patients. In a dose-response curve carried out with increasing PLT number per MNC, progressive inhibition was found, reaching to 62.6% and 49.5%, respectively, to phytohemagglutinin and IL2 lymphoproliferative response and 87.8% in IL2 production, at 80 PLTs/MNC.


Geographical distribution of ixodid ticks and tick-borne pathogens of domestic animals in Ethiopia: a systematic review.
In Ethiopia, ixodid ticks and associated tick-borne pathogens (TBPs) are of great importance from both a veterinary and public health point of view. This review aimed at compiling available published data on the distribution of ixodid tick species and TBPs in the country. A standard review approach was employed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Published peer-reviewed articles and theses/dissertations reporting on ixodid ticks and TBPs in Ethiopia were searched using different keywords in many electronic databases including PubMed, Scopus, Web of Science, Google Scholar, African Journals OnLine, and institutional repositories. Articles were screened based on inclusion and exclusion criteria using the PRISMA flowchart. Data were retrieved from eligible articles and recorded in a preformed data record sheet. Descriptive statistics were employed to present data using graphs. QGIS (Quantum GIS) software version 3.4.5 was used to show the distribution of ixodid tick species and TBPs. Overall, 35 articles that met the inclusion criteria were included in this review. Of these, 24 articles report only on ixodid ticks of domestic animals, six articles report only on TBPs in livestock or ticks, and five articles report on both ticks and TBPs in either animals or ticks. Of these studies, 54% were in the Oromia region, while only 3% of studies were in the Benishangul-Gumuz region. The Gambela region lacked studies on ticks and TBPs. At least 19 ixodid tick species have been recorded from different domestic animals including cattle, small ruminants, donkeys, horses, camels, dogs, and cats. Morphological characterization appears to be the sole method of tick species identification in the country. The distribution and abundance of specific tick species depend on geographical locations and agroecological factors. Sixteen molecularly confirmed TBPs have been identified in animal and tick tissue using molecular methods from only four administrative regions, despite the wide distribution of ticks. Among TBPs, five Anaplasma, two Ehrlichia, two Rickettsia, five Theileria, two Babesia, and one Coxiella species are the major pathogens in both livestock and humans. Many ixodid ticks circulate in a wide geographical zone of Ethiopia. However, the limited reports on TBPs at the country level in general, and the absence of either tick or TBP reports around the border region with neighboring countries in particular, highlights the need for further study.


Influence of continuous use of a vacuum-forming machine for mouthguard thickness after thermoforming.
Mouthguards can reduce the risk of sports-related injuries such as tooth fracture or avulsion, but the sheet material and thickness have a large effect on their efficacy and safety. The aim of this study was to investigate the effect of the continuous use of a vacuum-forming machine on mouthguard thickness. Ethylene vinyl acetate sheets and olefin copolymer sheets were used for thermoforming with a vacuum-forming machine. The working model was trimmed to a height of 23 mm at the maxillary central incisor and 20 mm at maxillary first molar. During molding, the model was placed at the center of the vacuum unit. Three molding conditions were investigated (i) molding was carried out after the sag at the center of the softened sheet was 15 mm below the clamp (control); (ii) sheet heating started 5 minutes after the control, and molding in the same way as the control (AF5); and (iii) sheet heating started 10 minutes after the control, and molding in the same way as the control (AF10). Under each condition, vacuum forming was conducted for 30 seconds. Sheet thickness after fabrication was determined for the incisal edge, labial surface, cusp, and buccal surface using a special caliper accurate to 0.1 mm. The differences of the molding conditions on the thickness in each sheet material were analyzed by one-way analysis of variance and Bonferroni's multiple comparison tests. For both sheet materials, significant differences between the control and AF5 were observed at all measurement points (P<.01), but not between the control and AF10. Compared with the control, AF5 was thinner and AF10 was a similar thickness. The continuous use of a vacuum-forming machine led to a reduction in the thickness of the mouthguard. Intervals of 10 minutes are necessary to achieve consistent molding.