Determination of selected antibiotics in the Victoria Harbour and the Pearl River, South China using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.
Nine selected antibiotics in the Victoria Harbour of Hong Kong and the Pearl River at Guangzhou, South China, were analyzed using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. The results showed that the concentrations of antibiotics were mainly below the limit of quantification (LOQ) in the marine water of Victoria Harbour. However, except for amoxicillin, all of the antibiotics were detected in the Pearl River during high and low water seasons with the median concentrations ranging from 11 to 67 ng/L, and from 66 to 460 ng/L, respectively; and the concentrations in early spring were about 2-15 times higher than that in summer with clearer diurnal variations. It was suggested that the concentrations of antibiotics in the high water season were more affected by wastewater production cycles due to quick refreshing rate, while those in the low water season may be more sensitive to the water column dynamics controlled by tidal processes in the river.


Flow and heat transfer in Sisko fluid with convective boundary condition.
In this article, we have studied the flow and heat transfer in Sisko fluid with convective boundary condition over a nonisothermal stretching sheet. The flow is influenced by non-linearly stretching sheet in the presence of a uniform transverse magnetic field. The partial differential equations governing the problem have been reduced by similarity transformations into the ordinary differential equations. The transformed coupled ordinary differential equations are then solved analytically by using the homotopy analysis method (HAM) and numerically by the shooting method. Effects of different parameters like power-law index n, magnetic parameter M, stretching parameter s, generalized Prandtl number Pr and generalized Biot number γ are presented graphically. It is found that temperature profile increases with the increasing value of M and γ whereas it decreases for Pr. Numerical values of the skin-friction coefficient and local Nusselt number are tabulated at various physical situations. In addition, a comparison between the HAM and exact solutions is also made as a special case and excellent agreement between results enhance a confidence in the HAM results.


Polymer-Based Wound Dressings Loaded with Ginsenoside Rg3.
The skin, the largest organ in the human body, mainly plays a protective role. Once damaged, it can lead to acute or chronic wounds. Wound healing involves a series of complex physiological processes that require ideal wound dressings to promote it. The current wound dressings have characteristics such as high porosity and moderate water vapor permeability, but they are limited in antibacterial properties and cannot protect wounds from microbial infections, which can delay wound healing. In addition, several dressings contain antibiotics, which may have bad impacts on patients. Natural active substances have good biocompatibility; for example, ginsenoside Rg3 has anti-inflammatory, antibacterial, antioxidant, and other biological activities, which can effectively promote wound healing. Some researchers have developed various polymer wound dressings loaded with ginsenoside Rg3 that have good biocompatibility and can effectively promote wound healing and reduce scar formation. This article will focus on the application and mechanism of ginsenoside Rg3-loaded dressings in wounds.


Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas.
The role of prophylactic antibacterial agents after chemotherapy remains controversial. We conducted a randomized, double-blind, placebo-controlled trial in patients who were receiving cyclic chemotherapy for solid tumors or lymphoma and who were at risk for temporary, severe neutropenia (fewer than 500 neutrophils per cubic millimeter). Patients were randomly assigned to receive either 500 mg of levofloxacin once daily or matching placebo for seven days during the expected neutropenic period. The primary outcome was the incidence of clinically documented febrile episodes (temperature of more than 38 degrees C) attributed to infection. Secondary outcomes included the incidence of all probable infections, severe infections, and hospitalization but did not include a systematic evaluation of antibacterial resistance. A total of 1565 patients underwent randomization (784 to placebo and 781 to levofloxacin). The tumors included breast cancer (35.4 percent), lung cancer (22.5 percent), testicular cancer (14.4 percent), and lymphoma (12.8 percent). During the first cycle of chemotherapy, 3.5 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 7.9 percent in the placebo group (P<0.001). During the entire chemotherapy course, 10.8 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 15.2 percent of patients in the placebo group (P=0.01); the respective rates of probable infection were 34.2 percent and 41.5 percent (P=0.004). Hospitalization was required for the treatment of infection in 15.7 percent of patients in the levofloxacin group and 21.6 percent of patients in the placebo group (P=0.004). The respective rate of severe infection was 1.0 percent and 2.0 percent (P=0.15), with four infection-related deaths in each group. An organism was isolated in 9.2 percent of probable infections. Among patients receiving chemotherapy for solid tumors or lymphoma, the prophylactic use of levofloxacin reduces the incidence of fever, probable infection, and hospitalization.


Systemic low-dose aspirin and clopidogrel independently attenuate reflex cutaneous vasodilation in middle-aged humans.
Chronic systemic platelet cyclooxygenase (COX) inhibition with low-dose aspirin [acetylsalicylic acid (ASA)] significantly attenuates reflex cutaneous vasodilation in middle-aged humans, whereas acute, localized, nonisoform-specific inhibition of vascular COX with intradermal administration of ketorolac does not alter skin blood flow during hyperthermia. Taken together, these data suggest that platelets may be involved in reflex cutaneous vasodilation, and this response is inhibited with systemic pharmacological platelet inhibition. We hypothesized that, similar to ASA, specific platelet ADP receptor inhibition with clopidogrel would attenuate reflex vasodilation in middle-aged skin. In a double-blind crossover design, 10 subjects (53+/-2 yr) were instrumented with four microdialysis fibers for localized drug administration and heated to increase body core temperature [oral temperature (Tor)] 1 degrees C during no systemic drug (ND), and after 7 days of systemic ASA (81 mg) and clopidogrel (75 mg) treatment. Skin blood flow (SkBF) was measured using laser-Doppler flowmetry over each site assigned as 1) control, 2) nitric oxide synthase inhibited (NOS-I; 10 mM NG-nitro-L-arginine methyl ester), 3) COX inhibited (COX-I; 10 mM ketorolac), and 4) NOS-I+COX-I. Data were normalized and presented as a percentage of maximal cutaneous vascular conductance (%CVCmax; 28 mM sodium nitroprusside+local heating to 43 degrees C). During ND conditions, SkBF with change (Delta) in Tor=1.0 degrees C was 56+/-3% CVCmax. Systemic low-dose ASA and clopidogrel both attenuated reflex vasodilation (ASA: 43+/-3; clopidogrel: 32+/-3% CVCmax; both P<0.001). In all trials, localized COX-I did not alter SkBF during significant hyperthermia (ND: 56+/-7; ASA: 43+/-5; clopidogrel: 35+/-5% CVCmax; all P>0.05). NOS-I attenuated vasodilation in ND and ASA (ND: 28+/-6; ASA: 25+/-4% CVCmax; both P<0.001), but not with clopidogrel (27+/-4% CVCmax; P>0.05). NOS-I+COX-I was not different compared with NOS-I alone in either systemic treatment condition. Both systemic ASA and clopidogrel reduced the time required to increase Tor 1 degrees C (ND: 58+/-3 vs. ASA: 45+/-2; clopidogrel: 39+/-2 min; both P<0.001). ASA-induced COX and specific platelet ADP receptor inhibition attenuate reflex vasodilation, suggesting platelet involvement in reflex vasodilation through the release of vasodilating factors.


Multiple functions of the S-phase checkpoint mediator.
There is mounting evidence that replication defects are the major source of spontaneous genomic instability in cells, and that S-phase checkpoints are the principal defense against such instability. The S-phase checkpoint mediator protein Mrc1/Claspin mediates the checkpoint response to replication stress by facilitating phosphorylation of effector kinase by a sensor kinase. In this review, the multiple functions and the regulation of the S-phase checkpoint mediator are discussed.


Self-selection of a high calcium diet by vitamin D-deficient lactating rats increases food consumption and milk production.
Lactating and nonlactating rats, both deficient and replete in cholecalciferol, were allowed a free selection among three diets containing 0.47% Ca, 0.3% P (normal Ca, normal P diet); 2.0% Ca, 0.3% P (high Ca diet); and 0.47% Ca, 1.0% P (high P diet). An additional group of vitamin D-deficient lactating rats was fed only the normal Ca, normal P diet. Vitamin D-deficient rats showed a strong selection preference for the high Ca diet but avoided the high P diet, whereas cholecalciferol-replete rats consumed the normal Ca, normal P diet predominantly. Compared to the nonselecting rats, the selection of the high Ca diet by the lactating rats deficient in vitamin D resulted in an increase in plasma calcium levels, hypophosphatemia, a doubling of food consumption, a reduction in maternal body weight loss and a stimulation of milk production as indicated by pup growth. These results demonstrate that vitamin D-deficient rats select a high Ca diet and that the decrease in milk production found in vitamin D deficiency results from a decrease in food consumption and that this anorexia is at least partially dependent on the hypocalcemia normally occurring in vitamin D deficiency.


Endothelial marker-expressing stromal cells are critical for kidney formation.
Kidneys are highly vascularized and contain many distinct vascular beds. However, the origins of renal endothelial cells and roles of the developing endothelia in the formation of the kidney are unclear. We have shown that the Foxd1-positive renal stroma gives rise to endothelial marker-expressing progenitors that are incorporated within a subset of peritubular capillaries; however, the significance of these cells is unclear. The purpose of this study was to determine whether deletion of Flk1 in the Foxd1 stroma was important for renal development. To that end, we conditionally deleted Flk1 (critical for endothelial cell development) in the renal stroma by breeding-floxed Flk1 mice (Flk1fl/fl ) with Foxd1cre mice to generate Foxd1cre; Flk1fl/fl (Flk1ST-/- ) mice. We then performed FACsorting, histological, morphometric, and metabolic analyses of Flk1ST-/- vs. control mice. We confirmed decreased expression of endothelial markers in the renal stroma of Flk1ST-/- kidneys via flow sorting and immunostaining, and upon interrogation of embryonic and postnatal Flk1ST-/- mice, we found they had dilated peritubular capillaries. Three-dimensional reconstructions showed reduced ureteric branching and fewer nephrons in developing Flk1ST-/- kidneys vs. Juvenile Flk1ST-/- kidneys displayed renal papillary hypoplasia and a paucity of collecting ducts. Twenty-four-hour urine collections revealed that postnatal Flk1ST-/- mice had urinary-concentrating defects. Thus, while lineage-tracing revealed that the renal cortical stroma gave rise to a small subset of endothelial progenitors, these Flk1-expressing stromal cells are critical for patterning the peritubular capillaries. Also, loss of Flk1 in the renal stroma leads to nonautonomous-patterning defects in ureteric lineages.


Radiofrequency-based carotid wall tracking: a comparison between two different systems.
A direct measurement of carotid stiffness implies an accurate assessment of changes in carotid diameter and pressure during cardiac cycle. Radiofrequency-based wall-tracking systems (WTS) are capable to track arterial wall movement with adequate spatial and temporal resolution, and to provide carotid pressure estimate from calibrated distension waveforms. The aim of the present study was to compare the values of carotid distension and beta-stiffness index acquired in the same population by two commercially available WTS, in order to determine whether their measures can be pooled in clinical studies. In addition, a local carotid pulse pressure (PP) obtained from calibrated distension waveforms was compared with that obtained from pressure waveforms. In 105 patients, right common carotid artery (CCA) systo-diastolic excursions were assessed during the same session and by the same operator both by WTS implemented in Esaote system (QAS, MyLab) and in Aloka system (E-track; Alpha 10). In 78 patients, carotid PP was also estimated by applanation tonometry. Despite comparable blood pressure and heart rate values during the two acquisitions, CCA distension was significantly lower (363 ± 162 vs. 458 ± 176 μm, P < 0.0001) and beta-stiffness index (11.9 ± 5.5 vs. 9.4 ± 3.8, P < 0.0001) higher with Esaote as compared to Aloka. PP obtained from calibrated pressure and distension waveforms was comparable (42.6 ± 11.4 vs. 43.0 ± 10.7 mmHg, P = 0.51). The values of carotid distension and stiffness obtained by two different WTS are not interchangeable and cannot be merged into a common database. Calibrated distension curves may provide an acceptable estimate of local carotid pressure.


Gene coexpression analysis offers important modules and pathway of human lung adenocarcinomas.
Lung adenocarcinomas injured greatly on the people worldwide. Although clinic experiments and gene profiling analyses had been well performed, to our knowledge, systemic coexpression analysis of human genes for this cancer is still limited to date. Here, using the published data GSE75037, we built the coexpression modules of genes by Weighted Gene Co-Expression Network Analysis (WGCNA), and investigated function and protein-protein interaction network of coexpression genes by Database for Annotation, visualization, and Integrated Discovery (DAVID) and String database, respectively. First, 11 coexpression modules were conducted for 5,000 genes in the 83 samples recently. Number of genes for each module ranged from 90 to 1,260, with the mean of 454. Second, interaction relationships of hub-genes between pairwise modules showed great differences, suggesting relatively high scale independence of the modules. Third, functional enrichment of the coexpression modules showed great differences. We found that genes in modules 8 significantly enriched in the biological process and/or pathways of cell adhesion, extracellular matrix (ECM)-receptor interaction, focal adhesion, and PI3K-Akt signaling pathway, and so forth. It was inferred as the key module underlying lung adenocarcinomas. Furthermore, PPI analysis revealed that the genes COL1A1, COL1A2, COL3A1, CTGF, and BGN owned the largest number of adjacency genes, unveiling that they may functioned importantly during the occurrence of lung adenocarcinomas. To summary, genes involved in cell adhesion, ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathway play crucial roles in human lung adenocarcinomas.


Enantiomeric separation of seven β-agonists by NACE-Study of chiral selectivity with diacetone-d-mannitol-boric acid complex.
A rapid and effective nonaqueous capillary electrophoresis (NACE)-ultraviolet (UV) method was developed for the enantiomeric separation of seven β-agonists. Diacetone-d-mannitol-boric acid complex was used as a new chiral selector. It was in situ synthesized by the reaction of diacetone-d-mannitol and boric acid in methanol medium containing triethylamine. The effects of diacetone-d-mannitol, boric acid, and triethylamine concentrations on the enantioseparation were carefully investigated. Under the optimized conditions, baseline enantioseparation could be obtained for six of the tested β-agonists within 12min. These results were better than that obtained with d-mannitol-boric acid complex in previous work. 11B nuclear magnetic resonance (11B NMR) was applied to determine the fraction of boron species and confirm the formation of diacetone-d-mannitol-boric acid complex. Validation of the established NACE method was also carried out according to ICH guidelines. Calibration curves showed good linearity with correlation coefficients (r)≥0.9992 over a certain concentration range for each enantiomer of the tested five β-agonists. The relative standard deviations (RSDs) of intra-day precisions and inter-day precisions of migration times were ≤1.4% (n=6), and ≤6.3% (n=10), respectively. That of peak areas were ≤3.7% (n=6), and ≤5.6% (n=10), respectively. The limits of detection (LODs) and the limits of quantitation (LOQs) based on the signal-to-noise ratios of 3 and 10 were found below 1.25μgmL-1 and 5.00μgmL-1, respectively. The proposed method was successfully applied to the determination of clenbuterol enantiomers in a multi-component pharmaceutical dosage form called "Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution".


A qualitative descriptive study of the lived experiences of school-aged children with epilepsy.
The purpose of this study was to gain a better understanding of children's personal experiences with epilepsy to guide health care providers in providing care to these children. This qualitative study examined the experiences of eight children, ages 9 to 12 years, who have epilepsy. The audiotaped interviews were guided by eight open-ended questions designed by the researchers. The taped interviews were later transcribed and discussed by the researchers. Patterns identified from the interviews were (a) my seizure medications; (b) seizures are not fun; (c) what my friends think about seizures; (d) what I do for fun; and (e) ways I live with my seizures. Several themes were identified from each of the patterns. These findings suggest that children with epilepsy dislike having seizures and taking seizure medication; friends provide significant relationships and support; children with epilepsy participate in sports; and children with epilepsy are cognizant of auras and ways to prevent seizures. Through these school-aged children's experiences and perceptions, pediatric nurse practitioners and other health care providers can establish developmentally appropriate, comprehensive methods to help these children cope with epilepsy and seizures.


The peripheral processes of spiral ganglion cells after intracochlear application of brain-derived neurotrophic factor in deafened guinea pigs.
To characterize the effects of deafening and subsequent treatment with brain-derived neurotrophic factor (BDNF) on the peripheral processes (PPs) of spiral ganglion cells (SGCs) in guinea pigs. BDNF may prevent degeneration of neural structures after loss of hair cells with possible relevance for cochlear implant candidates. Guinea pigs were deafened with a combination of kanamycin and furosemide. Two weeks after deafening, intracochlear BDNF treatment was started with osmotic pumps for 4 weeks. Two weeks after cessation of BDNF treatment, the cochleae were analyzed. PPs were counted and morphologically characterized with respect to myelination, size, and shape. Deafening reduced the number of PPs. We found that BDNF treatment, started 2 weeks after deafening, significantly reduced this degenerative effect. The remaining processes showed an altered morphology; compared with normal, the size was reduced in deafened untreated animals and increased in BDNF-treated animals. The myelin sheath seemed thinner in BDNF-treated animals. We conclude that BDNF has potential as an agent that can improve the interface between cochlear implants and the auditory periphery.


Eco-Friendly Recycling of Lithium Batteries for Extraction of High-Purity Metals.
The significant increase in lithium batteries consumption produces a significant quantity of discarded lithium-ion batteries (LIBs). On the one hand, the shortage of high-grade ores leads to the necessity of processing low-grade ores, which contain a low percentage of valuable metals in comparison to the discarded LIBs that contain a high percentage of these metals, which enhances the processing of the discarded LIBs. On the other hand, the processing of discarded LIBs reduces the negative environmental effects that result from their storage and the harmful elements contained in their composition. Hence, the current study aims at developing cost-effective and ecofriendly technology for cobalt and lithium metal ion recovery based on discarded LIBs. A novel synthesized solid-phase adsorbent (TZAB) was utilized for the selective removal of cobalt from synthetic solutions and spent LIBs. The synthesized TZAB adsorbent was characterized by using 13C-NMR, GC-MS, FT-IR, 1H-NMR, and TGA. The factors affecting the adsorption of cobalt and lithium ions from synthetic solutions and spent LIBs, including the sorbent dose, pH, contact time, temperature, and cobalt concentration were investigated. The conditions surrounding the recovery of cobalt and lithium from processing discarded LIBs, were investigated to optimize the maximum recovery. The Langmuir, Freundlich, and Dubinin-Radushkevich (D-R) isotherm models were used to study the kinetics of the adsorption process. The obtained results showed that high-purity CoC2O4 and Li3PO4 were obtained with a purity of 95% and 98.3% and a percent recovery of 93.48% and 95.76%, respectively. The maximum recovery of Co(II) from synthetic solutions was obtained at C0 = 500 mg·L-1, dose of 0.08 g, pH 7.5, T = 25 °C, and reaction time = 90 min. The collected data from Langmuir's isotherm and the adsorption processes of Co agree with the data predicted by the D-R isotherm models, which shows that the adsorption of Co(II) onto the TZAB seems to be chemisorption, and the results agree with the Langmuir and D-R isotherm models.


Hepatic glucocorticoid and α1- and β2-adrenergic receptors in calves change during neonatal maturation and are related to energy regulation.
Catecholamines and glucocorticoids are involved in fetal maturation of organ systems to prepare the fetus for extrauterine life. Calves, especially when born preterm, depend on function of the adrenergic system and the glucocorticoid axis to adapt energy metabolism for the neonatal period. We tested the hypothesis that hepatic glucocorticoid and α1- and β2-adrenergic receptors in neonatal calves are involved in adaptation of energy metabolism around birth and that respective binding capacities depend on stage of maturation during the neonatal period. Calves (n=7 per group) were delivered by section preterm (PT, 9d before term) or were born at term (full-term, FT; spontaneous vaginal delivery), or spontaneously born and fed colostrum for 4d (FTC). Blood samples were taken immediately after birth and before and 2h after feeding at 24h after birth (PT, FT) or on d 4 of life (FTC) to determine metabolic and endocrine changes. After slaughter at 26h after birth (PT, FT) or on d 4 of life (FTC), liver tissue was obtained to measure hepatic binding capacity of glucocorticoid and α1- and β2-adrenergic receptors. Maximal binding capacity and binding affinity were calculated by saturation binding assays using [(3)H]-prazosin and [(3)H]-CGP-12177 for determination of α1- and β2-adrenergic receptors, respectively, and [(3)H]-dexamethasone for determination of glucocorticoid receptor in liver. Additional liver samples were taken to measure mRNA abundance of glucocorticoid and α1- and β2-adrenergic receptors, of key enzymes and factors related to hepatic lipid metabolism, and of insulin-like growth factor 1 (IGF1). Plasma concentrations of β-hydroxybutyrate and leptin changed with time, and leptin concentrations were affected by stage of maturation. The binding capacities for hepatic glucocorticoid and β2-adrenergic receptors as well as gene expression of IGF1 were greater in FTC than in FT and PT, and binding affinity for β2-adrenergic receptor was lowest in PT. The binding capacity of hepatic α1-adrenergic receptor was greatest in FTC and greater in FT than in PT. The binding capacities of glucocorticoid and α1-adrenergic receptors were mainly related to variables of glucose and lipid metabolism. In conclusion, our results indicate dependence of hepatic glucocorticoid and adrenergic receptors on stage of maturation in neonatal calves and emphasize the association of α1-adrenergic receptor and glucocorticoid receptor with neonatal glucose and lipid metabolism.


k-Fold Cross-Validation Can Significantly Over-Estimate True Classification Accuracy in Common EEG-Based Passive BCI Experimental Designs: An Empirical Investigation.
In passive BCI studies, a common approach is to collect data from mental states of interest during relatively long trials and divide these trials into shorter "epochs" to serve as individual samples in classification. While it is known that using k-fold cross-validation (CV) in this scenario can result in unreliable estimates of mental state separability (due to autocorrelation in the samples derived from the same trial), k-fold CV is still commonly used and reported in passive BCI studies. What is not known is the extent to which k-fold CV misrepresents true mental state separability. This makes it difficult to interpret the results of studies that use it. Furthermore, if the seriousness of the problem were clearly known, perhaps more researchers would be aware that they should avoid it. In this work, a novel experiment explored how the degree of correlation among samples within a class affects EEG-based mental state classification accuracy estimated by k-fold CV. Results were compared to a ground-truth (GT) accuracy and to "block-wise" CV, an alternative to k-fold which is purported to alleviate the autocorrelation issues. Factors such as the degree of true class separability and the feature set and classifier used were also explored. The results show that, under some conditions, k-fold CV inflated the GT classification accuracy by up to 25%, but block-wise CV underestimated the GT accuracy by as much as 11%. It is our recommendation that the number of samples derived from the same trial should be reduced whenever possible in single-subject analysis, and that both the k-fold and block-wise CV results are reported.


Effects of functional exercises in the warm-up on sprint performances.
The process of warming up prepares athletes for subsequent stress and increases their level of performance. Functional exercises are often included in warm-up programs for power sports, although a positive effect of functional exercises has not been confirmed. The aim of this study was to measure a possible effect of functional exercises on sprint performance included in a warm-up program. A total of 121 elite youth soccer players between 13 and 18 years of age participated in this study and performed 2 different warm-up programs. The first program (NWP) consisted of 5 minutes of nonspecific running, coordination exercises, stretching, and acceleration runs. The second program (WPS) was the same with additional functional exercises. The subjects were tested performing linear sprints of approximately 30 m and change-of-direction sprints of approximately 10 m. The t-test for dependent samples showed significant differences between the groups for each segment of the linear sprint (p < 0.01 for 5 m; p < 0.001 for 10, 15, 20, 25, and 30 m); however, the effect sizes are small. Also, in the change-of-direction sprint, the t-test showed significant differences between the groups (p < 0.01 for 10 m left, 10 m right; p < 0.001 for 5 m right). These effect sizes are also small. In the change-of-direction sprint time for 5 m left, the data showed no significant differences between the groups. The results show no effects of functional exercises on sprint performance that are implemented in addition to a general warm-up. It appears that a general warm-up program, such as the NWP, generates sufficient activation of the performance-limiting muscles for sprint performance. Functional exercises did not lead to a supplemental activation with a positive effect on sprint performance. Therefore, a warm-up for sprint performance should contain nonspecific running, coordination exercises, stretching exercises, and acceleration runs. These components lead to sufficient activation of the muscles involved in sprint performance. Coaches should use the limited time available for warm-up to work efficiently. The recommendation for warm-up is to pass on functional exercises that have no additional effect in enhancing performance.


Holocene reconfiguration and readvance of the East Antarctic Ice Sheet.
How ice sheets respond to changes in their grounding line is important in understanding ice sheet vulnerability to climate and ocean changes. The interplay between regional grounding line change and potentially diverse ice flow behaviour of contributing catchments is relevant to an ice sheet's stability and resilience to change. At the last glacial maximum, marine-based ice streams in the western Ross Sea were fed by numerous catchments draining the East Antarctic Ice Sheet. Here we present geomorphological and acoustic stratigraphic evidence of ice sheet reorganisation in the South Victoria Land (SVL) sector of the western Ross Sea. The opening of a grounding line embayment unzipped ice sheet sub-sectors, enabled an ice flow direction change and triggered enhanced flow from SVL outlet glaciers. These relatively small catchments behaved independently of regional grounding line retreat, instead driving an ice sheet readvance that delivered a significant volume of ice to the ocean and was sustained for centuries.


Triterpene acids from Euscaphis japonica and assessment of their cytotoxic and anti-NO activities.
Six new triterpenoids, euscaphic acids G-L (1-6), along with nine known triterpene acids, and two known lignans were isolated from the ethanolic extract of the twigs of Euscaphis japonica. This is the first report concerning 1α,3β-dihydroxy-12-oleanen-28-oic acid isolated from a natural source. The structures of the new compounds were established by spectroscopic analysis. The cytotoxic and anti-NO production activities for the isolates are also evaluated and discussed; compound 1, hederagenin (11), and arjunic acid (12) showed significant cytotoxicity against NCI-H460 cells, HT-29 cells, and CEM cells (IC₅₀ = 1.64 ± 0.87, 2.11 ± 1.54, 1.73 ± 0.64 µM, respectively). Some of the isolated triterpenoids showed marginal inhibitions on NO production induced by LPS.


Phosphotyrosine-specific phosphatase PTP-SL regulates the ERK5 signaling pathway.
The duration and the magnitude of mitogen-activated protein kinase (MAPK) activation specifies signal identity and thus allows the regulation of diverse cellular functions by the same kinase cascade. A tight and finely tuned regulation of MAPK activity is therefore critical for the definition of a specific cellular response. We investigated the role of tyrosine-specific phosphatases (PTPs) in the regulation of ERK5. Although unique in its structure, ERK5 is activated in analogy to other MAPKs by dual phosphorylation of threonine and tyrosine residues in its activation motif. In this study we concentrated on whether and how PTP-SL, a kinase-interacting motif-containing PTP, might be involved in the down-regulation of the ERK5 signal. We found that both proteins interact directly with each other in vitro and in intact cells, resulting in mutual modulation of their enzymatic activities. PTP-SL is a substrate of ERK5 and independent of phosphorylation binding to the kinase enhances its catalytic phosphatase activity. On the other hand, interaction with PTP-SL not only down-regulates endogenous ERK5 activity but also effectively impedes the translocation of ERK5 to the nucleus. These findings indicate a direct regulatory influence of PTP-SL on the ERK5 pathway and corresponding downstream responses of the cell.


[Four-year follow-up of thyrotoxic patients treated with antithyroid drugs bases on thyroid suppressibility-Prognostic value of the 20-min 131-I thyroid uptake (author's transl)].
Out of 77 thyrotoxic patients treated with Carbimazole (30-15 mg/day) in combination with 1-triiodothyronine (75 micron/day) for 5-48 months applying 20-min 131I-thyroid uptake test at the end of treatment as a parameter for thyroid suppressibility, 39 cases (51%) have maintained euthyroid state for more than 4 years, while 20 (26%) relapsed within 3 months and the remaining 18 (23%) recurred within 6 years after antithyroid-drug (ATD) therapy. The predictable value of 20-min 131I-thyroid uptake was useful for distinguishing relapses from others, but there was no statiscally significant difference between recurrent cases and remittent ones. Since the negative correlation between the 20-min 131I-thyroid uptake and the recurrent phase was noted, the continuation of ATD therapy until the uptake reaches below 8% postpones this phase of recurrence.


Addressing Racism in Ethics Consultation: An Expansion of the Four-Box Method.
AbstractRacism is a pervasive issue in patient care and a key social determinant of health. Clinical ethicists, like others involved in patient care, have a duty to recognize and respond to racism on both individual and systems-wide levels to improve patient care. Doing so can be challenging and, like other skills in ethics consultation, may benefit from specialized training, standardized tools and approaches, and practice. Learning from existing frameworks and tools, as well as building new ones, can help guide clinical ethicists to systematically approach racism as it affects clinical cases. Here, we propose an expansion of the commonly used four-box method to clinical ethics consultation, where racism is considered as a potential factor in each of the four boxes. We apply this method to two clinical cases to highlight ethically salient information that might be missed using the standard formulation of the four boxes but captured with the expanded version. We argue that this expansion of an existing clinical ethics consultation tool is ethically justified insofar as it (a) creates a more just approach, (b) supports individual consultants and services, and (c) facilitates communication in contexts where racism impinges on effecting good patient care.


The Adolescent Condition in Thomas Hardy's The Woodlanders.
In The Woodlanders, Hardy examines the intersections between adolescence as scientific fact and adolescence as utilitarian economic construction. Hardy posits that the emergence of adolescence as a social category provides an opportunity for further, excessive control of young women in a patriarchal society when science is taken at its word, but, paradoxically, also opens up a space for a new kind of freedom and rebellion when the adolescent condition of nineteenth-century scientific theorists is seized for the very subversive qualities which the Victorians oppose.


[The treatment of "critical ischemia" of the limbs in endarteritis obliterans by thickening of the tibial bone].
The autors report their experience in the treatment of the "critical ischemia" in 8 patients with arterial occlusion of the lower limbs in endarteritis obliterans. All patients were treated by thickening of the tibia using the Ilizarov apparatus for distraction osteosynthesis. In all cases the operative treatment ensured lowering of the amputation level, forming of the functional stump and long-lasting remission of the illness.


Characterisation of CO(2) and HCO(3) (-) uptake in the cyanobacterium Synechocystis sp. PCC6803.
The availability of a complete genome database for the cyanobacterium Synechocystis sp. PCC6803 (glucose-tolerant strain) has raised expectations that this organism would become a reference strain for work aimed at understanding the CO(2)-concentrating mechanism (CCM) in cyanobacteria. However, the amount of physiological data available has been relatively limited. In this report we provide data on the relative contributions of net HCO(3) (-) uptake and CO(2) uptake under steady state photosynthetic conditions. Cells were compared after growth at high CO(2) (2% v/v in air) or limiting CO(2) conditions (20 ppm CO(2)). Synechocystis has a very high dependence on net HCO(3) (-) uptake at low to medium concentrations of inorganic carbon (Ci). At high Ci concentrations net CO(2) uptake became more important but did not contribute more than 40% to the rate of photosynthetic O(2) evolution. The data also confirm that high Ci cells of Synechocystis sp. PCC6803 possess a strong capacity for net HCO(3) (-) uptake under steady state photosynthetic conditions. Time course experiments show that induction of maximal Ci uptake capacity on a shift from high CO(2) to low CO(2) conditions was near completion by four hours. By contrast, relaxation of the induced state on return of cells to high CO(2), takes in excess of 230 h. Experiments were conducted to determine if Synechocystis sp. PCC6803 is able to exhibit a 'fast induction' response under severe Ci limitation and whether glucose was capable of causing a rapid inactivation in Ci uptake capacity. Clear evidence for either response was not found.


Systemic administration of 3-bromopyruvate reveals its interaction with serum proteins in a rat model.
3-bromopyruvate (3-BrPA) is a glycolytic inhibitor that affects cancer cells by targeting energy metabolism. Preclinical reports have established that a 1.75 mM dose of 3-BrPA is effective and sufficient to inhibit tumor growth when administered under a loco-regional approach (intraarterial and intratumoral). This loco-regional therapeutic dose was found to be nontoxic when given systemically as well. Yet, the mechanism underlying this lack of toxicity of 1.75 mM 3-BrPA during systemic delivery is unknown. Here, we investigated the mechanism associated with the lack of organ toxicity when 1.75 mM 3-BrPA was administered systemically using radiolabeled (14C)-3-BrPA in Sprague-Dawley rats. Data obtained from tissue-autoradiography of rats infused with 14C-3-BrPA showed strong 14C-signal in tissue sections of various organs except the brain corroborating that 3-BrPA does not cross the blood-brain barrier. Significantly, Hematoxylin & Eosin staining and apoptosis assay of tissue sections positive for 14C-signal showed no signs of toxicity or apoptosis. Convincingly, the 14C-signal observed in tissue-autoradiography emanates from 3-BrPA that is non-reactive or non-toxic, hence we further investigated whether the lack of toxicity is due to its interaction or alkylation with serum components. Analysis of serum proteins by 1D and 2D-gel electrophoretic autoradiography showed that 14C-BrPA selectively binds to peptides of molecular mass ~50-60 kDa. Mass spectrometry data suggested that 14C-BrPA could interact with alpha1-antitrypsin and a peptide of albuminoid-family. Our data indicate that selective interaction of 3-BrPA with serum proteins could contribute to the apparent lack of tissue-toxicity at the indicated close when the drug is given systematically in Sprague-Dawley rats.


1,4-Phenylene-Incorporated Decaphyrin(188.8.131.52.0.1.0.1.0.0): Synthesis, Structure, and Topological Chirality.
Expanded porphyrins represent emerging structures in realizing topological chirality; however, their inherent flexibility has hampered the effective chiral resolution. Herein, we rationally designed a decaphyrin 9, which could be separated into its enantiomers in the free-base form. The enantiomers showed noteworthy chiroptical properties, e.g., the intense circular dichroism response in the visible spectrum, and high absorption dissymmetry factors (gabs) of 0.036 at 618 nm. Theoretical analyses further explained the origin of the high gabs value.


Assessment of neovascularization within carotid plaques in patients with ischemic stroke.
To assess neovascularization within human carotid atherosclerotic soft plaques in patients with ischemic stroke. Eighty-one patients with ischemic stroke and 95 patients without stroke who had soft atherosclerotic plaques in the internal carotid artery were studied. The thickest soft plaque in each patient was examined using contrast-enhanced ultrasound. Time-intensity curves were collected from 5 s to 3 min after contrast injection. The neovascularization within the plaques in the internal carotid artery was evaluated using the ACQ software built into the scanner by 2 of the experienced investigators who were blinded to the clinical history of the patients. Ischemic stroke was present in 7 of 33 patients (21%) with grade I plaque, in 14 of 51 patients (28%) with grade II plaque, in 26 of 43 patients (61%) with grade III plaque, and in 34 of 49 patients (69%) with grade IV plaque (P < 0.001 comparing grade IV plaque with grade I plaque and with grade II plaque and P = 0.001 comparing grade III plaque with grade I plaque and with grade II plaque). Analysis of the time intensity curves revealed that patients with ischemic stroke had a significantly higher intensity of enhancement (IE) than those without ischemic stroke (P < 0.01). The wash-in time (WT) of plaque was significantly shorter in stroke patients (P < 0.05). The sensitivity and specificity for IE in the plaque were 82% and 80%, respectively, and for WT were 68% and 74%, respectively. There was no significant difference in the peak intensity or time to peak between the 2 groups. This study shows that the higher the grade of plaque enhancement, the higher the risk of ischemic stroke. The data suggest that the presence of neovascularization is a marker for unstable plaque.


[Antigenic similarity of the hemagglutinins of human and animal influenza A viruses studied by immunoadsorption].
Antigenic relationships between human influenza A viruses containing hemagglutinins of HO and H1 subtypes and animal and avian influenza viruses Hsw1 and Hav5 were studied by immunoadsorption using inorganic base of the sorbent. Direct and indirect relations due to the presence in hemagglutinin of common antigenic determinants and hapten groups were revealed. The strains representing drift variations within one subtype differed by the spectrum of hapten determinants typical of other subtypes. No common determinant typical for all members of this group was isolated.


Clustering by genetic ancestry using genome-wide SNP data.
Population stratification can cause spurious associations in a genome-wide association study (GWAS), and occurs when differences in allele frequencies of single nucleotide polymorphisms (SNPs) are due to ancestral differences between cases and controls rather than the trait of interest. Principal components analysis (PCA) is the established approach to detect population substructure using genome-wide data and to adjust the genetic association for stratification by including the top principal components in the analysis. An alternative solution is genetic matching of cases and controls that requires, however, well defined population strata for appropriate selection of cases and controls. We developed a novel algorithm to cluster individuals into groups with similar ancestral backgrounds based on the principal components computed by PCA. We demonstrate the effectiveness of our algorithm in real and simulated data, and show that matching cases and controls using the clusters assigned by the algorithm substantially reduces population stratification bias. Through simulation we show that the power of our method is higher than adjustment for PCs in certain situations. In addition to reducing population stratification bias and improving power, matching creates a clean dataset free of population stratification which can then be used to build prediction models without including variables to adjust for ancestry. The cluster assignments also allow for the estimation of genetic heterogeneity by examining cluster specific effects.


Wnt6 maintains anterior escort cells as an integral component of the germline stem cell niche.
Stem cells reside in a niche, a local environment whose cellular and molecular complexity is still being elucidated. In Drosophila ovaries, germline stem cells depend on cap cells for self-renewing signals and physical attachment. Germline stem cells also contact the anterior escort cells, and here we report that anterior escort cells are absolutely required for germline stem cell maintenance. When escort cells die from impaired Wnt signaling or hid expression, the loss of anterior escort cells causes loss of germline stem cells. Anterior escort cells function as an integral niche component by promoting DE-cadherin anchorage and by transiently expressing the Dpp ligand to promote full-strength BMP signaling in germline stem cells. Anterior escort cells are maintained by Wnt6 ligands produced by cap cells; without Wnt6 signaling, anterior escort cells die leaving vacancies in the niche, leading to loss of germline stem cells. Our data identify anterior escort cells as constituents of the germline stem cell niche, maintained by a cap cell-produced Wnt6 survival signal.


Diapause in ticks of the medically important Ixodes ricinus species complex.
Four members of the Ixodes ricinus species complex, Ixodes pacificus, Ixodes persulcatus, Ixodes ricinus and Ixodes scapularis, have, between them, a worldwide distribution within the northern hemisphere. They are responsible for the transmission of several animal and human pathogens, including the causal agents of Lyme borreliosis, tick-borne encephalitis, human granulocytic anaplasmosis and human babesiosis. Despite the importance of these ticks as vectors, the knowledge and understanding of the role that diapause plays in their complex life cycles are confused and incomplete. In view of the continuing geographic spread of these tick species, as well as the effects of climate change on vector-borne diseases, it is timely to encourage research on diapause phenomena to improve understanding of their biology and of pathogen transmission dynamics. In our review we seek to clarify thinking on the topic and to address gaps in our knowledge that require the attention of researchers.


Differentiating selves facilitates group outcomes.
The target article proposed that differentiation of selves is a crucial moderator of group outcomes, such that differentiation of selves contributes to beneficial outcomes of groups while limiting undesirable outcomes. In this response, we aim to complement the target article by refining and expanding several aspects of the theory. We address our conceptualization of optimal group functioning, clarify the term differentiation of selves, comment on the two-step nature of our model, offer theoretical connections and extensions, and discuss applications and opportunities for future research.


[Not Available].
The problem of 'reality' and 'realism' is rarely discussed in medieval medical texts, although medieval medicine is based on objectivity. There are three reasons why medieval physicians were so sure about their image of human nature: the convincing model of humoral pathology, the undoubted truth of tradition, and the suggestive similarities between worldly things and their presumed divine purpose. Thus, individual cases were only examples of the common theory of medicine and were by no means able to change it.


From therapeutic hypothermia towards targeted temperature management: a decade of evolution.
More than a decade after the first randomised controlled trials with targeted temperature management (TTM), it remains the only treatment with proven favourable effect on postanoxemic brain damage after out-of-hospital cardiac arrest. Other well-known indications include neurotrauma, subarachnoidal haemorrhage, and intracranial hypertension. When possible pitfalls are taken into consideration when implementing TTM, the side effects are manageable. After the recent TTM trials, it seems that classic TTM (32-34°C) is as effective and safe as TTM at 36°C. This supports the belief that fever prevention is one of the pivotal mechanisms that account for the success of TTM. Uncertainty remains concerning cooling method, timing, speed of cooling and rewarming. New data indicates that TTM is safe and feasible in cardiogenic shock, one of its classic contra-indications. Moreover, there are limited indications that TTM might be considered as a therapy for cardiogenic shock per se.


Reading-to-Writing Mediation model of higher-order literacy.
Writing difficulties frequently manifest comorbidly with reading challenges, and reading is implicated in particular acts of writing, such as reviewing and editing. Despite what is known, however, there remain significant barriers to understanding the nature of reading-writing relations, as few studies are comprehensive in the number and types of literacy skills evaluated. This study consists of a secondary data analysis of two studies employing structural equation modeling (SEM) to evaluate relations among reading and writing components skills independently, using the Direct and Inferential Mediation Model (DIME) of reading comprehension and Not-so-Simple View of Writing (NSVW) as theoretical frameworks. We examine relations between reading and writing components from these models with a sample of upper elementary students with/at-risk for learning disabilities (n = 405). Lower-order components included word reading, vocabulary, handwriting and spelling. Higher-order components included background knowledge, reading strategies, inferencing, planning, editing, and revision. The literacy outcomes were oral and silent reading fluency, reading comprehension, and writing quality and productivity. We systematically build a Reading-to-Writing Mediation (RWM) model by first merging the DIME and NSVW components in a direct effects model (Aim 1), expanding the joint model to include reading and writing fluency (Aim 2), evaluating indirect effects between DIME and NSVW component skills (Aim 3), and finally, evaluating indirect effects with reading and writing fluency (Aim 4). The findings suggest that higher order fluency and comprehension skills are differentially related to writing activities and products. The pattern of results helps elucidate the mechanisms of how various reading and writing skills transfer and relate. The results have implications for targeted and implicit instruction in multicomponent interventions and the use of screeners to identify areas of risk.


Prevention of HIV among drug users.
The relationship between injection drug use and HIV was established early in the HIV epidemic, and injection drug use has continued to be an important risk factor for HIV throughout the world. This panel included 4 papers related to HIV prevention among drug users, focusing on effective prevention strategies, the importance of organizing the AIDS-affected community, the impact of knowledge of serostatus on risk behaviors, and developing interventions for drug-using homosexual and bisexual men. These papers, addressing various aspects of the epidemic and methods to enhance prevention efforts, all indicate that although extensive knowledge regarding how to reduce HIV risks among drug users has accumulated, many areas for further research and intervention development remain.


Bacterial growth inhibition by amniotic fluid. III. Demonstration of the variability of bacterial growth inhibition by amniotic fluid with a new plate-count technique.
The ability of 50 human amniotic fluid samples to inhibit the growth of Escherichia coli was measured with a new semimicro plate-count technique. A range from bacterial growth-sustaining fluid to bactericidal fluid was observed. When the inhibitory capacities of the fluid samples were correlated with gestational age, a progressive increase was obtained with maximum inhibitory capacity at 36 to 40 weeks. All fluid samples obtained before 20 weeks' gestation were capable of supporting bacterial growth. Fluid samples of 36 to 40 weeks' gestation were all bactericidal or bacteriostatic. More variability in inhibitory capacity was seen after 40 weeks, with an over-all loss of inhibition observed.


The 677C --> T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in epileptic patients affected by systemic lupus erythematosus.
Neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) is considered as one of the major manifestations of the disease. Epilepsy has been documented in about 10% of patients with systemic lupus erythematosus (SLE). It is well known that vascular damage in SLE occurs because of multiple mechanisms including hypercoagulation. It has been recently reported that in SLE patients raised levels of homocysteine are associated with arterial thrombosis. Hyperhomocysteinaemia is a condition due to both genetic and non-genetic factors. The most common genetic defect in homocysteine metabolism is a decreased activity of a common 5,10-methylenetetrahydrofolate reductase (MTHFR) variant (677C -->T, a thermolabile form). In this paper we describe the epileptic manifestations in six out of 55 SLE patients. Seizures were the SLE onset symptom for three patients, appeared during the active disease in two cases, and occurred during a period of clinical remission in one patient. In all cases we documented the association of epilepsy with the MTHFR mutation: the homozygosity form was present in one case (16.7%), and heterozygosity in five cases (83.3%). Nevertheless, levels of homocysteine in plasma were in the normal range. Moreover, we found a decrease in the level of S protein values in one case, a high titre positivity of anticardiolipin antibodies (aCL) (IgG and IgM) in three patients and low titre positivity (IgG) in one patient, and lupus anticoagulant (LAC) positivity in four cases. In conclusion, we believe that the abnormalities of coagulation present in our patients could be related to epileptogenesis or to an alteration of the seizure threshold.


Isolation and structural characteristics of a monoclonal antibody-defined cross-reactive phospholipid antigen from Mycobacterium tuberculosis and Mycobacterium leprae.
A low molecular weight antigen of Mycobacterium leprae and other mycobacteria was previously defined in our laboratory by means of IgG2a monoclonal antibody termed L4. The antigen had an apparent molecular mass of 4.5-6 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was assumed to be a glycoprotein on the basis of its staining with periodic acid Schiff and sensitivity to periodate treatment. In the present work, the cross-reactive and phospholipidic nature of the antigen, present in Mycobacterium tuberculosis as well as in M. leprae sonicates, was demonstrated and this enabled us to undertake its purification from crude M. tuberculosis phospholipidic extracts. The L4-reactive antigen from M. tuberculosis called L4-PIM, was purified by means of silicic acid high pressure liquid chromatography. Its characterization by gas chromatography and FAB-MS showed the antigen to be the common mycobacterial dimannosylated phosphatidylinositol (PIM2), the structure of which had been previously established by others (Lee, Y. C., and Ballou, C. E. (1964) J. Biol. Chem. 239, 1316-1327; Lee, Y. C., and Ballou, C. E. (1965) J. Biochem. (Tokyo) 4, 1395-1404). Delineation of the L4 epitope on M. tuberculosis L4-PIM revealed the involvement of the axial 2-hydroxyl of the alpha-D-mannosyl residues, without any detectable contribution from the myo-inositol. Consequently, L4 was shown to react with PIM5, the structure of which contains twice the number of epitopes as does PIM2. By using both immunostained thin layer chromatography and indirect enzyme-linked immunosorbent assay, similar L4-PIM epitopes were demonstrated in M. leprae sonicate, thereby explaining the cross-reactive nature of the L4-monoclonal antibody. Antibodies of IgG class directed against M. tuberculosis L4-PIM were detectable in sera from patients with leprosy, but no evidence of T cell reactivity to L4-PIM was obtained. The demonstration of a correlation of anti-L4-PIM IgG and anti-disacharide-conjugated bovine serum albumin IgM antibody titers in the sera of leprosy patients indicates that measurement of antibodies directed against L4-PIM may have the potential to be used as a complementary assay to the disaccharide-conjugated bovine serum albumin test for diagnosis and monitoring of patients undergoing leprosy therapy.


A discriminant analysis approach to morphological regionalization in the European Late Mesolithic.
The morphological regionalization of European Mesolithic populations was studied by discriminant analysis. Samples from four localities were compared employing craniometric variables. The general conclusion was that there is evidence for regionalization in the Late mesolithic in Europe, and a clinical pattern of variation was not detected. These results are in agreement with archaeological reconstructions of the population structure in the Late Mesolithic Europe.


Single-shot afocal three-dimensional microscopy.
Fourier-basis agile structured illumination sensing (F-BASIS) employs acousto-optically synthesized moving interference patterns, sparse RF-encoded aperture synthesis, nonredundant spatiotemporal frequency multiplexing, and single-pixel detection to measure dense clouds of three-dimensional (3D) Fourier samples without scanning, enabling high-speed focus-free volume microscopy. We present 3D fluorescence imaging results using F-BASIS, including an unprecedented wide-field single-shot volumetric measurement in under 10 ms. The unique capabilities provided by F-BASIS could prove instrumental for capturing fleeting dynamic processes such as neuron signaling in 3D.


Hemophilic pseudotumor of the first lumbar vertebra.
Hemophilic pseudotumor involving the spine is extremely uncommon and presents a challenging problem. Preoperative planning, angiography, intra and perioperative monitoring with factor VIII cover and postoperative care for hemophilic pseudotumor is vital. Recognition of the artery of Adamkiewicz in the thoracolumbar junction helps to avoid intraoperative neurological injury. We report the case of a 26-year-old male patient with hemophilia A, who presented with a massive pseudotumor involving the first lumbar vertebra and the left iliopsoas. Preoperative angiography revealed the artery of Adamkiewicz arising from the left first lumbar segmental artery. Excision of pseudotumor was successfully carried out with additional spinal stabilization. At 2 years followup, there was no recurrence and the patient was well stabilized with a satisfactory functional status. Surgical excision gives satisfactory outcome in such cases.


Mortality Characteristic and Prediction of Nasopharyngeal Carcinoma in China from 1991 to 2013.
To analyze the mortality distribution of nasopharyngeal carcinoma in China from 1991 to 2013, to predict the mortality in the ensuing five years, and to provide evidence for prevention and treatment of nasopharyngeal carcinoma. Mortality data for Nasopharyngeal Carcinoma in China from 1991 to 2013 were used to describe its epidemiological characteristics, such as the change of the standardized mortality rate, sex and age differences, urban-rural differences. Trend-surface analysis was used to study the geographical distribution of the mortality. Curve estimation, time series, gray modeling, and joinpoint regression were used to predict the mortality for the ensuing five years in the future. In China, the standardized mortality rate of Nasopharyngeal Carcinoma increased with time from 1996, reaching the peak values of 1.45 /105 at the year of 2002, and decreased gradually afterwards. With males being 1.51 times higher than females, and the city had a higher rate than the rural during the past two decades. The mortality rate increased from age 40. Geographical analysis showed the mortality rate increased from middle to southern China. The standardized mortality rate of Nasopharyngeal Carcinoma is falling. The regional disease control for Nasopharyngeal Carcinoma should be focused on Guangdong province of China, and the key targets for prevention and treatment are rural men, especially after the age of 40. The mortality of Nasopharyngeal Carcinoma will decrease in the next five years.


Successful Treatment of Rheumatoid Lymphedema with Lymphatic Venous Anastomosis.
Rheumatoid lymphedema is a rare but severely disabling condition caused by reduced lymphatic drainage. Most treatment methods are conservative and may lead to the exacerbation of lymphedema. Lymphatic venous anastomosis (LVA) is an effective treatment for lymphedema after surgery involving the lymphatic system, such as lymph node dissection for cancer treatment. LVA has not been used to treat rheumatoid lymphedema. We present a case of rheumatoid lymphedema treated with surgical procedures, including LVA. Following LVA, objective and subjective symptom relief was noted, along with decreased swelling and pain in the affected area. The postoperative course was uneventful. LVA for the treatment of rheumatoid lymphedema may provide definitive clinical improvements.


Medication use and hospital-acquired acute kidney injury: an electronic health record-based study.
Medications remain an important contributor to the development of acute kidney injury (AKI). This study aimed to examine associations between (i) administration of medications known to reduce glomerular filtration rate (GFR), that is, GFR modifiers and subsequent hospital-acquired AKI; and (ii) potentially medication-related AKI and patient adverse outcomes. A retrospective cohort study utilising electronic health record data of patients admitted to a tertiary hospital in Australia in 2015. Timing of medication administration was compared with timing of AKI development. AKI cases were identified using an algorithm based on serum creatinine level changes. Multilevel regression models were applied with adjustment for relevant demographic and clinical factors. Among 11 503 admissions, AKI was identified in 955 patients (8.3%) and 637 (66.7% of 955) were preceded by administration of a GFR modifier. Patients without prior AKI were 17% more likely to develop AKI after administration of these medications (adjusted odds ratio 1.17, 95% confidence interval (CI) 1.003-1.37). Older age and comorbidity with diabetes, acute myocardial infarction, peripheral vascular disease, liver cirrhosis and multiple myeloma were also significant predictors. Patients with potentially medication-related AKI were 11.69 times more likely to die in hospital (95% CI 7.84-17.43) and stayed 3.49 times longer in hospital (95% CI 3.26-3.73), compared with those without AKI. Administration of medications contributing to the reduction of GFR is associated with an increased risk of hospital-acquired AKI and worse patient outcomes. Caution is required when prescribing these medications to patients at risk of developing AKI, and monitoring patients for deterioration is needed if administered.


[Histological investigation of nail growth in human embryos and regrowth of nail after its removal in adult monkeys--with reference to clinical observation in injuries to the nail and its surrounding tissues].
As the basis to develop adequate treatments which can preserve the nail plate or assure its regrowth in frequently encountered injuries to the nail-surrounding tissues, a histological investigation was made of nail growth in human embryos and regrowth of nail after its removal in adult monkeys. The author's investigation in these two series indicated the following. Firstly the nail plate composed of parakeratotic layer is produced solely of "nail matrix", thus, supporting Zaias' and opposing Lewis' theory as to the nail production. Secondly though the normal, completely formed nail matrix and nail bed have no granulosa cell nor horny layer, the nail bed is temporarily covered with "false nail" which contains these two layers during the process of embryonal nail growth as well as during that of regrowth after its removal. This "false nail" well incorporates with the volar surface of growing or regrowing nail plate, and is gradually pushed distally as the nail grows and stretches distally . These findings raise a question why healthy nail does not grow over ordinary skin graft placed on the nail bed damaged by trauma. Is there any essential difference between "false nail" and ordinary skin graft, though both having these two layers in common? The author thinks there must be and presumes that it lies in the difference of turn-over time as exemplified with autoradiographical study by Zaias, i.e. turn-over time of germinative layers of healthy nail bed is much slower than in ordinary skin, therefore not so thick horny layer as in ordinary skin is formed by the time the growing or regrowing nail plate spread over it, which allows "incorporation" between palmar surface of the growing nail and germinative layer of the nail bed. On the contrary, too thick horny layer provided or formed in the grafted ordinary skin does not allow the "incorporation" between these tissues. Clinical observations coincide with the above result and presumption.


Vesicular glutamate transporter 1 immunoreactivity in extrinsic and intrinsic innervation of the rat esophagus.
Encouraged by the recent finding of vesicular glutamate transporter 2 (VGLUT2) immunoreactivity (-ir) in intraganglionic laminar endings (IGLEs) of the rat esophagus, we investigated also the distribution and co-localization patterns of VGLUT1. Confocal imaging revealed substantial co-localization of VGLUT1-ir with selective markers of IGLEs, i.e., calretinin and VGLUT2, indicating that IGLEs contain both VGLUT1 and VGLUT2 within their synaptic vesicles. Besides IGLEs, we found VGLUT1-ir in both cholinergic and nitrergic myenteric neuronal cell bodies, in fibers of the muscularis mucosae, and in esophageal motor endplates. Skeletal neuromuscular junctions, in contrast, showed no VGLUT1-ir. We also tested for probable co-localization of VGLUT1-ir with markers of extrinsic and intrinsic esophageal innervation and glia. Within the myenteric neuropil we found, besides co-localization of VGLUT1 and substance P, no further co-localization of VGLUT1-ir with any of these markers. In the muscularis mucosae some VGLUT1-ir fibers were shown to contain neuronal nitric oxide synthase (nNOS)-ir. VGLUT1-ir in esophageal motor endplates was partly co-localized with vesicular acetylcholine transporter (VAChT)/choline acetyltransferase (ChAT)-ir, but VGLUT1-ir was also demonstrated in separately terminating fibers at motor endplates co-localized neither with ChAT/VAChT-ir nor with nNOS-ir, suggesting a hitherto unknown glutamatergic enteric co-innervation. Thus, VGLUT1-ir was found in extrinsic as well as intrinsic innervation of the rat esophagus.


Electrocardiographic screening by special purpose computer. Correlation with twelve-lead electrocardiogram.
An electrocardiometer (ECM) which computes the T/R ratio of Lead I and simultaneously prints out Lead I was used to screen 1,004 consecutive hospitalized patients for EKG abnormalities. When the combined meter and Lead I print out analyses were used, 77.9% of abnormal EKG's were identified with a false-positive rate of less than 4%. The method is highly specific for detecting EKG abnormalities associated with anterior and lateral left ventricular disease. It could be used as an inexpensive mass screening device for electrocardiographic risk factors associated with coronary disease.


Prenatal development of the cochlear nerve in the albino rat.
Twenty-eight prenatal (14 to 20 days) Wistar albino rats were studied with Cajal-de Castro's silver reduced stain. The histological sections were oriented in a parasagittal oblique plane, parallel to the cochlear root, in order to observe the origin, course and destination of the cochlear fibres in as few consecutive sections as possible. In all the prenatal days studied, the fibres arising in the first half coil of the cochlea (hook's bundle), show a different orientation than those of the other cochlear nerve fibres, which constitute the spiralized bundle, originating in the basal, medial and apical portions of the cochlea. The hook-bundle does not participate in the curling of the cochlear nerve and it describes a particular course. At first, its fibres are situated in a lateral position in the nerve when it is inside the internal auditive duct. Then, the hook-fibres take a postero-inferior position just at the entry of the bulbar cochlear nuclei region. Furthermore, we have seen no hook's afferents branching in the ventral cochlear nucleus, and it could be suggested that these fibres project directly to the superficial dorso-medial area of the postero-ventral cochlear nucleus.


[Eukaryotic antibiotic peptides: a new alternative in clinical practice?].
Eukaryotic antibiotic peptides are key components of innate immunity. They act as a first barrier against invading pathogens. Expectations about their clinical use have been raised as they are active against a wide range of pathogens, and unlikely to induce resistance. Both characteristics are related to their lethal mechanism, based on interaction with anionic phospholipids in the outer facet of the cytoplasmic membrane of the pathogens, leading to permeabilization. This review will especially focus on antibiotic peptides of human origin. Their mechanism of action, strategies of pathogen resistance, and role in activities other than microbicidal effect will be described. Practical applications and prospects of future use in anti-infectious therapy will also be discussed.


Field Experiment of a Three-Chemical Controlled-Release Dispensers to Attract Codling Moth (Cydia pomonella) (Lepidoptera: Tortricidae).
Male and female codling moths, Cydia pomonella (Lepidoptera: Tortricidae), were shown to be attracted to a three-chemical kairomonal lure consisting of pear ester, acetic acid, and n-butyl sulfide. A controlled-release device based on sachets was developed in the laboratory and field tested to optimize the attractiveness of C. pomonella to this combination of attractants, and to decrease material costs associated with the controlled-release of these chemicals. The lure was most effective when pear ester was released from a separate dispenser than when combined acetic acid and n-butyl sulfide. We found that acetic acid and n-butyl sulfide can be combined into one device without decreasing C. pomonella trap catches and that there is minimal pear release rate before trap catch is negatively affected. A sachet-based controlled-release system of pear ester, acetic acid, n-butyl sulfide is a cost-effective alternative to a vial and septa controlled-release system and allows for easier quantification of ideal release rates. A reduction in material costs associated with management are important in promoting the adoption of attract-and-kill and mass-trapping paradigms for C. pomonella management. These findings also have important consequences in interpreting studies that use different loads of pear ester, and emphasize the need to better understand the release rates of attractants.


High quality draft genome sequence of Segniliparus rugosus CDC 945(T)= (ATCC BAA-974(T)).
Segniliparus rugosus represents one of two species in the genus Segniliparus, the sole genus in the family Segniliparaceae. A unique and interesting feature of this family is the presence of extremely long carbon-chain length mycolic acids bound in the cell wall. S. rugosus is also a medically important species because it is an opportunistic pathogen associated with mammalian lung disease. This report represents the second species in the genus to have its genome sequenced. The 3,567,567 bp long genome with 3,516 protein-coding and 49 RNA genes is part of the NIH Roadmap for Medical Research, Human Microbiome Project.


Cystadenocarcinoma (papillary cystadenocarcinoma) of the submandibular gland.
Cystadenocarcinoma (papillary cystadenocarcinoma) of the salivary gland is a rare malignant neoplasm. Major locations of this neoplasm are the parotid gland, the sublingual gland, and minor salivary glands, while occurrence in the submandibular gland is extremely rare. As far as we know, only one report, written in the French language, has been published concerning cystadenocarcinoma of the submandibular gland, but no report is available in the English language. In this report, we describe a case of cystadenocarcinoma arising from the submandibular gland of a 54-year-old male patient. The neoplasm is a low-grade carcinoma, and pre-operative examination may not show typical characteristics of malignant neoplasms. Therefore, as was true in this case, the differential diagnosis from benign lesions is sometimes difficult. This is the first report on cystadenocarcinoma of the submandibular gland in the English language and the first to show a computed tomography (CT) scan and magnetic resonance imaging (MRI) of this neoplasm in the submandibular gland.


Extracellular vesicles in the tumor microenvironment: Therapeutic resistance, clinical biomarkers, and targeting strategies.
Numerous studies have proved that cell-nonautonomous regulation of neoplastic cells is a distinctive and essential characteristic of tumorigenesis. Two way communications between the tumor and the stroma, or within the tumor significantly influence disease progression and modify treatment responses. In the tumor microenvironment (TME), malignant cells utilize paracrine signaling initiated by adjacent stromal cells to acquire resistance against multiple types of anticancer therapies, wherein extracellular vesicles (EVs) substantially promote such events. EVs are nanoscaled particles enclosed by phospholipid bilayers, and can mediate intercellular communications between cancerous cells and the adjacent microenvironment to accelerate pathological proceeding. Here we review the most recent studies of EV biology and focus on key cell lineages of the TME and their EV cargoes that are biologically active and responsible for cancer resistance, including proteins, RNAs, and other potentially essential components. Since EVs are emerging as novel but critical elements in establishing and maintaining hallmarks of human cancer, timely and insightful understanding of their molecular properties and functional mechanisms would pave the road for clinical diagnosis, prognosis, and effective targeting in the global landscape of precision medicine. Further, we address the potential of EVs as promising biomarkers in cancer clinics and summarize the technical improvements in EV preparation, analysis, and imaging. We highlight the practical issues that should be exercised with caution to guide the development of targeting agents and therapeutic methodologies to minimize cancer resistance driven by EVs, thereby allowing to effectively control the early steps of disease exacerbation.


Lethal Effects of Lambda-Cyhalothrin and its Commercial Formulation on Asian Longhorned Beetle (Coleoptera: Cerambycidae): Implications for Population Suppression, Tree Protection, Eradication, and Containment.
We evaluated the 24-h contact toxicity of lambda-cyhalothrin for adult Asian longhorned beetle, Anoplophora glabripennis Motschulsky, by using topical application. Results showed that beetles are sensitive to lambda-cyhalothrin: the LD50 and LD90 were 0.13639 and 0.78461 µg/beetle, respectively. Residual activity of a commercial formulation of lambda-cyhalothrin was evaluated in a walking bioassay: Adult beetles walked across the surface of Denier bands treated with a series of concentrations of the formulation and exposed to the natural environment for 10, 20, 45, 69, and 90 d. Beetle mortality was recorded after 24 h. At the dosages of 150, 300, 450, and 600 mg/liter, residual activity declined slowly over the 90-d test period. All dosages provided 100% mortality up to 20 d posttreatment. No significant differences were detected in mortality among the dosages at each test interval until day 90 posttreatment, when the 450 and 600 mg/liter doses provided 100% mortality, which was significantly greater than percentage mortality provided by the 150 (20%) and 300 mg/liter (50%) doses. The 1200, 1500, and 1800 mg/liter doses provided 100% mortality for 158 d. The formulation may represent a new, alternative and complementary control strategy against A. glabripennis due to its high toxicity to adult A. glabripennis, its long residual activity, its rapid knock-down ability, and its potential use in specialized areas where current control strategies are not desirable or feasible.


Photodynamic therapy: An adjunct to conventional root canal disinfection strategies.
Although chemical-based root canal disinfectants are important to reduce microbial loads and remove infected smear layer from root dentin, they have only a limited ability to eliminate biofilm bacteria, especially from root complexities. This paper explores the novel photodynamic therapy (PDT) for antimicrobial disinfection of root canals. The combination of an effective photosensitizer, the appropriate wavelength of light and ambient oxygen is the key factor in PDT. PDT uses a specific wavelength of light to activate a non-toxic dye (photosensitizer), leading to the formation of reactive oxygen species. These reactive oxygen molecules can damage bacterial proteins, membrane lipids and nucleic acids, which promote bacterial cell death. In, addition PDT may enhance cross-linking of collagen fibrils in the dentin matrix and thereby improving dentin stability. The concept of PDT is plausible and could foster new therapy concepts for endodontics. The available knowledge should enable and encourage steps forward into more clinical-oriented research and development. This article discusses PDT as related to root canal disinfection, including its components, mechanism of action, reviews the current endodontic literature and also highlights the shortcomings and advancements in PDT techniques.


Metastatic breast cancer patient perceptions of somatic tumor genomic testing.
To assess metastatic breast cancer (MBC) patient psychological factors, perceptions, and comprehension of tumor genomic testing. In a prospective, single institution, single-arm trial, patients with MBC underwent next-generation sequencing at study entry with sequencing results released at progression. Patients who completed surveys before undergoing sequencing were included in the present secondary analysis (n = 58). We administered four validated psychosocial measures: Center for Epidemiologic Studies Depression Scale, Beck Anxiety Inventory, Trust in Physician Scale, and Communication and Attitudinal Self-Efficacy scale for Cancer. Genetic comprehension was assessed using 7-question objective and 6-question subjective measures. Longitudinal data were assessed (n = 40) using paired Wilcoxon signed rank and McNemar's test of agreement. There were no significant differences between the beginning and end of study in depression, anxiety, physician trust, or self-efficacy (median time on study: 7.6 months). Depression and anxiety were positively associated with each other and both negatively associated with self-efficacy. Self-efficacy decreased from pre- to post-genomic testing (p = 0.05). Objective genetics comprehension did not significantly change from pre- to post-genomic testing, but patients expressed increased confidence in their ability to teach others about genetics (p = 0.04). Objective comprehension was significantly lower in non-white patients (p = 0.02) and patients with lower income (p = 0.04). This is the only study, to our knowledge, to longitudinally evaluate multiple psychological metrics in MBC as patients undergo tumor genomic testing. Overall, psychological dimensions remained stable over the duration of tumor genomic testing. Among patients with MBC, depression and anxiety metrics were negatively correlated with patient self-efficacy. Patients undergoing somatic genomic testing had limited genomic knowledge, which varied by demographic groups and may warrant additional educational intervention. NCT01987726, registered November 13, 2013.


Levels of cerebrospinal fluid nerve-growth factor differ in infantile autism and Rett syndrome.
Autism and Rett syndrome (RS) are both developmental disorders of unknown origin. Autism is a behaviourally defined syndrome. RS, which affects girls only, is characterized by a profound learning disability following early normal development, with a consistent cluster of clinical features. Differentiation of RS from infantile autism in the very early stages of the disorders is not always easy. Both syndromes still lack discriminative laboratory markers for accurate diagnosis and differentiation. We decided to compare the CSF nerve-growth factor (NGF) levels of children with infantile autism and children with RS using enzyme-linked immunosorbent assay (ELISA). Our findings of mainly normal CSF NGF in autism and low to negligible values in RS are in agreement with the different morphological and neurochemical findings (brain growth, affected brain areas, neurotransmitter metabolism) in the two syndromes. CSF NGF could be used as a biochemical marker for differentiation of patients with autism from those with RS.


Enhancing spatial skills of preschoolers from under-resourced backgrounds: A comparison of digital app vs. concrete materials.
Spatial skills support STEM learning and achievement. However, children from low-socioeconomic (SES) backgrounds typically lag behind their middle- and high-SES peers. We asked whether a digital educational app-designed to mirror an already successful, spatial assembly training program using concrete materials-would be as effective for facilitating spatial skills in under-resourced preschoolers as the concrete materials. Three-year-olds (N = 61) from under-resourced backgrounds were randomly assigned to a business-as-usual control group or to receive 5 weeks of spatial training using either concrete, tangible materials or a digital app on a tablet. The spatial puzzles used were an extension of items from the Test of Spatial Assembly (TOSA). Preschoolers were pretested and posttested on new two-dimensional (2D) TOSA trials. Results indicate that both concrete and digital spatial training increased performance on the 2D-TOSA compared to the control group. The two trainings did not statistically differ from one another suggesting that educational spatial apps may be one route to providing early foundational skills to children from under-resourced backgrounds.


[Determination of naftopidil and its main metabolite in plasma by high-performance liquid chromatography].
A method was developed for the determination of naftopidil (NAF) and its main metabolite desmethyl-naftopidil (DMN) in plasma by HPLC. A mixture of methanol, acetonitrile and 0.02 mol.L-1 K2HPO4 solution was used as mobile phase. Stationary phase was RP-C18. Propranolol was chosen as internal standard (IS), and the detector wavelength was 240 nm. Under these conditions, the retention times of IS, DMN and NAF were 6.2, 7.6 and 10.5 min respectively. Absolute recoveries from plasma were up to 93.4% (IS), 76.8% (DMN) and 80.2% (NAF). The assay was linear for DMN and NAF in the range of 10-800 ng.ml-1 plasma concentration, gamma = 0.9998. The lowest detection limits were 8 ng.ml-1 (DMN) and 5 ng.ml-1 (NAF), and the precisions within-day and day-to-day were no more than 6.3% for MDN and 11.6% for NAF. The drug concentration-time pattern of these two substances was also studied with this method. Result showed that naftopidil was quickly absorbed after p.o. and the concentration-time data were fitted to two compartment model, with half life (T1/2 beta) of 8.13 h.


The differential roles of shame and guilt in the relationship between self-discrepancy and psychological maladjustment.
The self-discrepancy theory proposes that having inconsistent self-representations can trigger feelings of shame and guilt, leading to experiences of depression and anxiety. The aim of this study was to determine the distinct characteristics of each shame and guilt in relation to the connection between actual/ideal self-discrepancy and depression, as well as actual/ought self-discrepancy and anxiety. A total of 403 participants completed an online questionnaire assessing their self-discrepancy, shame, guilt, depression, and anxiety. Correlational analysis and structural equation modeling (SEM) analysis were used to assess the goodness of fit of the proposed model and the structural relationships between the variables. The key findings were as follows: (1) There were positive correlations among actual/ideal self-discrepancy, actual/ought self-discrepancy, shame, guilt, depression, and anxiety; (2) Shame partially mediated the association between actual/ideal self-discrepancy and depression; and (3) Guilt fully mediated the association between actual/ought self-discrepancy and anxiety. These outcomes uphold the self-discrepancy theory by confirming a distinct intra-psychological process involving shame and guilt. Each type of self-discrepancy was related to experiences of depression and anxiety. Our data suggest that researchers and practitioners should prioritize shame and guilt when examining individuals' self-discrepancy and related mental health challenges.


Impact of mild traumatic brain injury on auditory brain stem dysfunction in mouse model.
The auditory brainstem response (ABR) is an electrophysiological test that examines the functionality of the auditory nerve and brainstem. Traumatic brain injury (TBI) can be detected if prolonged peak latency is observed in ABR measurements, since latency measures the neural conduction time in the brainstem, and an increase in latency can be a sign of pathological lesion at the auditory brainstem level. The ABR is elicited by brief sounds that can be used to measure hearing sensitivity as well as temporal processing. Reduction in peak amplitudes and increases in latency are indicative of dysfunction in the auditory nerve and/or central auditory pathways. In this study we used sixteen young adult mice that were divided into two groups: sham and mild traumatic brain injury (mTBI), with ABR measurements obtained prior to, and at 2, 6, and 14 weeks after injury. Abnormal ABRs were observed for the nine TBI cases as early as two weeks after injury and the deficits lasted for fourteen weeks after injury. Results indicated a significant reduction in the Peak 1 (P1) and Peak 4 (P4) amplitudes to the first noise burst, as well as an increase in latency response for P1 and P4 following mTBI. These results are the first to demonstrate auditory sound processing deficits in a rodent model of mild TBI.


[Pre- and postoperative thyroglobulin secretion into the blood in nodular goiter].
Serum thyroglobulin was measured in patients with a euthyroid, preclinically hyperthyroid or toxic uni- or multinodular goiter (n = 72) prior to and/or 3-12 months following selective resection of the nodular goiter tissue. A sharp decrease in the mean and individually elevated serum thyroglobulin values was observed postoperatively, with normal or undetectable values in 92% of the patients. The pre- and postoperative thyroglobulin levels in multinodular goiter patients with hyperthyroidism, preclinical hyperthyroidism and euthyroidism were 102 +/- 79 micrograms/l vs. 10 +/- 7 micrograms/l; 77 +/- 62 micrograms/l vs. 16 +/- 22 micrograms/l; and 76 +/- 82 micrograms/1 vs. 18 +/- 26 micrograms/1 respectively. The pre- and postoperative values in uninodular goiter patients with TRH-TSH unresponsiveness and with a normal TSH response were 84 +/- 60 micrograms/l vs. 10 +/- 8 micrograms/l, and 105 +/- 115 micrograms/1 vs. less than 6 micrograms/1 respectively. Thus, the elevation of serum thyroglobulin proved to be unrelated to TRH-TSH responsiveness and to thyroid hormone secretion, but to be related to the presence of nodular goiter tissue. Follicular nodules lack normal TSH dependence with respect to goiter maintenance and growth. The results suggest that serum thyroglobulin may represent a marker of autonomous thyroid growth.


Transcriptional regulatory network during axonal regeneration of dorsal root ganglion neurons: laser-capture microdissection and deep sequencing.
The key regulators and regeneration-associated genes involved in axonal regeneration of neurons after injury have not been clarified. In high-throughput sequencing, various factors influence the final sequencing results, including the number and size of cells, the depth of sequencing, and the method of cell separation. There is still a lack of research on the detailed molecular expression profile during the regeneration of dorsal root ganglion neuron axon. In this study, we performed laser-capture microdissection coupled with RNA sequencing on dorsal root ganglion neurons at 0, 3, 6, and 12 hours and 1, 3, and 7 days after sciatic nerve crush in rats. We identified three stages after dorsal root ganglion injury: early (3-12 hours), pre-regeneration (1 day), and regeneration (3-7 days). Gene expression patterns and related function enrichment results showed that one module of genes was highly related to axonal regeneration. We verified the up-regulation of activating transcription factor 3 (Atf3), Kruppel like factor 6 (Klf6), AT-rich interaction domain 5A (Arid5a), CAMP responsive element modulator (Crem), and FOS like 1, AP-1 transcription factor Subunit (Fosl1) in dorsal root ganglion neurons after injury. Suppressing these transcription factors (Crem, Arid5a, Fosl1 and Klf6) reduced axonal regrowth in vitro. As the hub transcription factor, Atf3 showed higher expression and activity at the pre-regeneration and regeneration stages. G protein-coupled estrogen receptor 1 (Gper1), interleukin 12a (Il12a), estrogen receptor 1 (ESR1), and interleukin 6 (IL6) may be upstream factors that trigger the activation of Atf3 during the repair of axon injury in the early stage. Our study presents the detailed molecular expression profile during axonal regeneration of dorsal root ganglion neurons after peripheral nerve injury. These findings may provide reference for the clinical screening of molecular targets for the treatment of peripheral nerve injury.


Effect of Citric Acid Surface Modification on Solubility of Hydroxyapatite Nanoparticles.
Worldwide, there is an amplified interest in nanotechnology-based approaches to develop efficient nitrogen, phosphorus, and potassium fertilizers to address major challenges pertaining to food security. However, there are significant challenges associated with fertilizer manufacture and supply as well as cost in both economic and environmental terms. The main issues relating to nitrogen fertilizer surround the use of fossil fuels in its production and the emission of greenhouse gases resulting from its use in agriculture; phosphorus being a mineral source makes it nonrenewable and casts a shadow on its sustainable use in agriculture. This study focuses on development of an efficient P nutrient system that could overcome the inherent problems arising from current P fertilizers. Attempts are made to synthesize citric acid surface-modified hydroxyapatite nanoparticles using wet chemical precipitation. The resulting nanohybrids were characterized using powder X-ray diffraction to extract the crystallographic data, while functional group analysis was done by Fourier transform infrared spectroscopy. Morphology and particle size were studied using scanning electron microscopy along with elemental analysis using energy-dispersive X-ray diffraction spectroscopy. Its effectiveness as a source of P was investigated using water release studies and bioavailability studies using Zea mays as the model crop. Both tests demonstrated the increased availability of P from nanohybrids in the presence of an organic acid compared with pure hydroxyapatite nanoparticles and rock phosphate.


Acute cold-restraint stress affects alpha 2-adrenoceptors in specific brain regions of the rat.
The effect of acute cold-restraint stress on binding of [3H]rauwolscine to alpha 2-adrenoceptors was investigated in 10 regions of rat brain. Acute stress: significantly decreased the density but had no significant effect on the affinity of binding sites in the hippocampus; decreased density and increased affinity in the amygdala; and increased density and decreased the affinity in the midbrain. Seven other brain regions showed no significant changes in binding parameters in response to stress. These results, together with previous findings in this laboratory showed that alteration by restraint stress of noradrenaline levels in amygdala and hippocampus, but not other regions, indicate an association between neurotransmitter turnover and receptor function.


The Role of mTORC1 Pathway and Autophagy in Resistance to Platinum-Based Chemotherapeutics.
Cisplatin (cis-diamminedichloroplatinum I) is a platinum-based drug, the mainstay of anticancer treatment for numerous solid tumors. Since its approval by the FDA in 1978, the drug has continued to be used for the treatment of half of epithelial cancers. However, resistance to cisplatin represents a major obstacle during anticancer therapy. Here, we review recent findings on how the mTORC1 pathway and autophagy can influence cisplatin sensitivity and resistance and how these data can be applicable for the development of new therapeutic strategies.


Inhibition of alpha-glucosidase by oleanolic acid and its synthetic derivatives.
Oleanolic acid (1) and five synthetic derivatives (2-6) were tested spectrophotometrically for inhibition of urease, beta-lactamase, acetyl cholinesterase and alpha-glucosidase. All products showed a positive response only against alpha-glucosidase but not against the other enzymes; IC(50) calculations showed that the dihydroxy-olide derivative (4) was the most potent among all tested samples.


[Osteocalcin, a key molecule for bone endocrine functions].
The maintenance of our physiological functions and their adaptive response to environmental changes depend on precise crosstalk between organs. Recent advances in mouse genetics have helped demonstrate that this holistic view of physiology extends to the skeletal system, where many unexpected signaling axes are found to play essential roles affecting numerous organs. After being long regarded as a static tissue, functioning merely as a structural support system, the skeleton has seen its image evolve into a much more complex picture. The skeleton reveals itself as a key endocrine organ for the homeostasis of our body, both by its central position in our body, but also by the large number of physiological functions it influences. In this review, we discuss the multiple endocrine roles of osteocalcin, an osteoclast-derived molecule (Ocn), where its functional importance has steadily increased over the last 15 years.


Echocardiographic feature of aortic arch pseudoaneurysm resulting from spontaneous aortic rupture.
Atraumatic, spontaneous aortic rupture is a rare but potentially lethal event. In this report, we present two unusual cases of aortic arch pseudoaneurysm resulting from spontaneous aortic rupture. The appearance of aortic arch pseudoaneurysm and the rupture area was clearly visualized with echocardiography, as well as by three-dimensional reconstruction of multislice computed tomography (3DCT) images.


Effectiveness of CT-guided percutaneous cordotomy in intractable cancer pain: Experience in 14 patients.
Severe and treatment-resistant pain is a major issue for patients with cancer. Cordotomy is an effective approach for addressing severe cancer-related pain. It is based on blocking the transmission of pain by damaging the lateral spinothalamic tract. Computed tomography guided cordotomy was performed on 14 patients who did not respond to medical and interventional pain management methods. Fourteen patients with cancer pain underwent CT-guided percutaneous cordotomy. Pain relief was reported in 86% of the patients. The visual analog scale values before and after cordotomy were compared and a significant difference was found (p = 0.0001). The improvement in the Karnofsky Performance Scale score of the patients was found to be statistically significant (p = 0.0001). We believe that CT-guided cordotomy, performed by experienced hands in a team of experienced individuals and applied to the right patients, is an effective treatment. However, it is crucial to exercise extreme caution regarding potential side effects and serious complications during the cordotomy procedure.


Prolonged radioprotective activity of WR-2721 linked to dextran.
The radioprotective agent WR-2721 was linked to dextran and poly(glutamic acid) respectively, to obtain a prolonged radioprotective ability. Male mice were administered these water soluble polymer conjugates one to 72 hours prior to a whole body irradiation with X-rays. A prolongation of radioprotective efficiency was achieved with two dextran-(WR-2721)-conjugates. For a period of 24 hours between administration, and irradiation dose reduction factors of 1.14 +/- 0.04 and 1.10 +/- 0.03 respectively were found. After 72 hours, no protective effect was observed. Histopathological investigations of the liver for formation of tumors 200 to 600 days after irradiation seems to indicate that a protective effect is not produced by the dextran-(WR-2721)-conjugates.


Relationship between abnormal TOX3 gene methylation and polycystic ovarian syndrome.
The purpose of this work was to examine the relationship between abnormal TOX3 gene methylation and the occurrence of polycystic ovarian syndrome (PCOS). We selected 30 patients with PCOS and 30 control volunteers. Serum luteinizing hormone, estradiol, testosterone, and thyroid stimulating hormone were detected, methylation, mRNA and protein level of TOX3 were measured. Serum luteinizing hormone, estradiol, testosterone, and thyroid stimulating hormone were significantly higher and follicle stimulating hormone and prolactin were significantly lower in PCOS patients than in the control group. Methylation of the promoter of TOX3 in serum and granular cells was significantly lower in PCOS than in the control group. The mRNA levels of TOX3 in serum were lower in the PCOS group. The levels of TOX3 protein in serum and granular cells was significantly lower in PCOS group than in the control group. Overall, abnormal TOX3 methylation possibly resulting in changes in TOX3 protein expression is closely related to the occurrence of PCOS and may play a role the development of the pathology.