Vibration-Induced Kinesthetic Illusions and Corticospinal Excitability Changes.
The authors' aim was to investigate the changes of corticospinal excitability during kinesthetic illusions induced by tendon vibration. Motor-evoked potentials in response to transcranial magnetic stimulation were recorded from the vibrated flexor carpi radialis and its antagonist, extensor carpi radialis. The illusions were evoked under vision conditions without feedback for the position of the wrist (open or closed eyes). In these two conditions motor-evoked potential changes during vibration in the antagonist were not identical. This discrepancy may be a result of 2 simultaneously acting, different and opposite influences and the balance between them depends on visual conditions. Thus, the illusion was accompanied by the facilitation of corticospinal excitability in both vibrated muscle and its antagonist.


Contributions of epsinR and gadkin to clathrin-mediated intracellular trafficking.
The precise functions of most of the proteins that participate in clathrin-mediated intracellular trafficking are unknown. We investigated two such proteins, epsinR and gadkin, using the knocksideways method, which rapidly depletes proteins from the available pool by trapping them onto mitochondria. Although epsinR is known to be an N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-specific adaptor, the epsinR knocksideways blocked the production of the entire population of intracellular clathrin-coated vesicles (CCVs), suggesting a more global function. Using the epsinR knocksideways data, we were able to estimate the copy number of all major intracellular CCV proteins. Both sides of the vesicle are densely covered, indicating that CCVs sort their cargo by molecular crowding. Trapping of gadkin onto mitochondria also blocked the production of intracellular CCVs but by a different mechanism: vesicles became cross-linked to mitochondria and pulled out toward the cell periphery. Both phenotypes provide new insights into the regulation of intracellular CCV formation, which could not have been found using more conventional approaches.


Concomitant length and diameter separation of single-walled carbon nanotubes.
Gel electrophoresis and column chromatography conducted on individually dispersed, ultrasonicated single-walled carbon nanotubes yield simultaneous separation by tube length and diameter. Electroelution after electrophoresis is shown to produce highly resolved fractions of nanotubes with average lengths between 92 and 435 nm. Separation by diameter is concomitant with length fractionation, and nanotubes that have been cut shortest also possess the greatest relative enrichments of large-diameter species. Longer sonication time causes increased electrophoretic mobility in the gels; thus, ultrasonic processing determines the degree of both length and diameter separation of the nanotubes. The relative quantum yield decreases nonlinearly as the nanotube length becomes shorter. These techniques constitute a preparative, scalable method for separating nanotubes by two important attributes required for electronic and sensor applications.


miR-181 regulates GRP78 and influences outcome from cerebral ischemia in vitro and in vivo.
MicroRNAs (miRNA) are short (~22nt) single stranded RNAs that downregulate gene expression. Although recent studies indicate extensive miRNA changes in response to ischemic brain injury, there is currently little information on the roles of specific miRNAs in this setting. Heat shock proteins (HSP) of the HSP70 family have been extensively studied for their multiple roles in cellular protection, but there is little information on their regulation by miRNAs. We used bioinformatics to identify miR-181 as a possible regulator of several HSP70 family members. We validated GRP78/BIP as a target by dual luciferase assay. In response to stroke in the mouse we find that miR-181 increases in the core, where cells die, but decreases in the penumbra, where cells survive. Increased levels of miR-181a are associated with decreased GRP78 protein levels, but increased levels of mRNA, implicating translational arrest. We manipulated levels of miR-181a using plasmid overexpression of pri-miR-181ab or mimic to increase, and antagomir or inhibitor to reduce levels. Increased miR-181a exacerbated injury both in vitro and in the mouse stroke model. Conversely, reduced levels were associated with reduced injury and increased GRP78 protein levels. Studies in C6 cells show that if GRP78 levels are maintained miR-181a no longer exerts a toxic effect. These data demonstrate that miR-181 levels change in response to stroke and inversely correlate with levels of GRP78. Importantly, reducing or blocking miR-181a protects the brain from stroke.


Iron indices and survival in maintenance hemodialysis patients with and without polycystic kidney disease.
Anemia is less prominent in patients with polycystic kidney disease (PKD). Such iron indices as ferritin and transferrin saturation (TSAT) values are used to guide management of anemia in individuals on maintenance hemodialysis (MHD). Optimal levels of correction of anemia and optimal levels of TSAT and ferritin are unclear in chronic kidney disease patients and have not been studied specifically in PKD. We studied 2969 MHD patients with and 128 054 patients without PKD from 580 outpatient hemodialysis facilities between July 2001 and June 2006. Using baseline, time-dependent and time-averaged values with unadjusted and multivariable adjusted analysis models, the survival predictabilities of TSAT and ferritin were studied. PKD patients were 58 ± 13 years old and included 46% women, whereas non-PKD patients were 62 ± 15 years old and 45% women. In both PKD and non-PKD patients, a time-averaged TSAT between 30 and 40% was associated with the lowest mortality. Time-averaged ferritin between 100 and <800 ng/mL was associated with the lowest mortality in PKD patients, although this range was 500 to <800 ng/mL in non-PKD patients. In MHD patients with and without PKD, there was a U-shaped relationship between the average TSAT and mortality, and a TSAT of 30-40% was associated with the best survival. However, an average ferritin of 100-800 ng/mL was associated with the best survival in PKD patients, whereas that of non-PKD patients was 500-800 ng/mL. Further studies in PKD and non-PKD patients are necessary to determine whether or not therapeutic attempts to keep TSAT and ferritin levels in these ranges will improve survival.


Proteus syndrome in adulthood.
Proteus syndrome is a very rare congenital condition comprising malformations and overgrowth of multiple sorts of tissue. It was described for the first time in 1979 and was termed Proteus syndrome in 1983. The authors describe a 37-year-old patient who was diagnosed initially as having Klippel-Trenaunay-Weber syndrome at the age of 10 years. The patient was operated for a major thoracic lymphatic malformation, which caused functional problems. The operation at older age for this large lymphatic malformation proved to be complex. In addition, the authors address the difficulties in diagnosing Proteus syndrome. Vascular malformations causing functional problems in adulthood require major surgical procedures with a high risk of postoperative complications.


Plasma alpha-glutathione S-transferase assessed as a marker of liver damage in patients with chronic hepatitis C.
alpha-Glutathione S-transferase (alpha-GST; EC 22.214.171.124) has been advocated as a better marker of hepatocellular damage than the transaminases in toxic and autoimmune hepatitis. We have assessed the potential interest of plasma alpha-GST determination in 94 anti-hepatitis C virus-positive patients with histologically proven chronic hepatitis C (34 women, 60 men, ages 40.0 +/- 11.9 years). Blood samples were assayed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase, alkaline phosphatase, and alpha-GST on the same day a liver biopsy was performed. alpha-GST concentrations were significantly above reference values in 64% of patients (compared with 58% for AST, 68% for ALT), and this increase was seen in 52% of patients with normal values for transaminases and a Knodell score > 3. Furthermore, there was a significant correlation between alpha-GST and lobular necrosis score (r = 0.31; P < 0.01). Our findings suggest that association of plasma alpha-GST with ALT may improve the biochemical assessment of liver damage in patients with chronic hepatitis C.


Therapeutic drug monitoring of lopinavir/ritonavir in pregnancy.
The aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV-infected pregnant women receiving lopinavir/ritonavir (LPV/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum. Women were enrolled in the study who were receiving the LPV/r tablet as part of their routine prenatal care. Demographic and clinical data were collected and LPV plasma (total) and ultrafiltrate (unbound) concentrations were determined in the first, second and third trimesters using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Postpartum sampling was performed where applicable. Antepartum and postpartum trough concentrations (C(trough) ) were compared independently [using analysis of variance (anova)] and on a longitudinal basis (using a paired t-test). Forty-six women were enrolled in the study (38 Black African). Forty women initiated LPV/r treatment in pregnancy. Median (range) gestation at initiation was 25 (15-36) weeks and median (range) baseline CD4 count and viral load were 346 (14-836) cells/μL and 8724 (<50-267408) HIV-1 RNA copies/mL, respectively. Forty women (87%) had LPV concentrations above the accepted minimum effective concentration for wild-type virus (MEC; 1000 ng/mL). Geometric mean (95% confidence interval [CI]) total LPV concentrations in the first/second [3525 (2823-4227) ng/mL; n=16] and third [3346 (2813-3880) ng/mL; n=43] trimesters were significantly lower relative to postpartum [5136 (3693-6579) ng/mL; n=12] (P=0.006). In a paired analysis (n=12), LPV concentrations were reduced in the third trimester [3657 (2851-4463) ng/mL] vs. postpartum (P=0.021). No significant differences were observed in the LPV fraction unbound (fu%). Conclusions The above target concentrations achieved in the majority of women and similarities in the fu% suggest standard dosing of the LPV/r tablet is appropriate during pregnancy. However, reduced LPV concentrations in the second/third trimesters and potentially compromised adherence highlight the need for TDM-guided dose adjustment in certain cases.


Knowledge and attitudes of nursing home staff and surveyors about the revised federal guidance for incontinence care.
We assessed nursing home staff and state nursing home surveyors regarding their knowledge and attitudes about urinary incontinence, its management, and the revised federal Tag F315 guidance for urinary incontinence. We conducted a questionnaire survey of a convenience sample of nursing home staff and state nursing home surveyors from a midwestern state attending two statewide workshops on the revised guidance. Of 558 attendees, 500 (85%) responded, including 39% of the state's directors of nursing and 57% of state nursing home surveyors. There were striking deficiencies in knowledge regarding urinary incontinence and catheter care, with significant discrepancies by type of respondent, particularly between state surveyors and nursing home staff. Staff cited documentation and staffing levels as the most frequent concerns about implementation. Open-ended responses reflected the divergence of concerns and antagonism among the stakeholders, and staff nurses' feeling that F315 violated residents' rights. The revised Tag F315 guidance will be unlikely to improve the quality of urinary incontinence care in nursing homes because of significant knowledge and attitudinal discrepancies between nursing home staff and state surveyors, facility staff's focus on documentation and staffing, and reliance on implementation strategies known to be ineffective. Federal, state, and other urinary incontinence guideline efforts should focus on managerial structures and methods to improve quality nursing home care. Research is needed to address how nursing home residents and families define and value "quality" urinary incontinence management and to incorporate these in quality-improvement strategies and measures.


Beneficial effects of a diabetes specific formula on insulin sensitivity and free fatty acid in patients with type 2 diabetes mellitus.
This prospective, randomized, controlled study was designed to investigate the effects of a diabetes specific formula (Diason low energy: 313.8 kJ/100 ml), compared with a standard formula, on insulin sensitivity, serum C peptide, serum lipids and free fatty acid (FFA) in type 2 diabetics. In total of 71 type 2 diabetics completed the study. Enteral formulas were given orally as the sole source of nutrition to the subjects for 6 days. Venous blood samples (0.5, 1, 2, 3 hours) were collected at day-7 after a 75 g oral glucose tolerance test (OGTT), day 1 after a standard test meal (1673.6 kJ) and after 6 days of either the test diabetes specific formula or a standard formula. Plasma glucose, serum insulin, C peptide and lipids were measured. After the intervention period, the diabetes specific formula resulted in a significantly lower postprandial rise in blood glucose concentrations at 0.5 hour (P < 0.05) and 1 hour (P < 0.01); significantly lower peak height of plasma glucose (P = 0.05); significantly lower plasma insulin concentrations at 0.5 hour (P < 0.01), 1 hour (P < 0.01) and 2 hours (P < 0.01); and a significantly lower plasma insulin peak compared to controls; both OGTT and a standard test meal (P < 0.05). The glucose and insulin area under the curve after the diabetes specific formula compared to the standard formula were significantly lower. The C peptide level was lower after 6 days of both nutrition formulas compare to 75 g OGTT, but not different from the standard mixed meal. Both formulas were well tolerated. In summary the diabetes specific formula with a relatively high monounsaturated fatty acid and high multi fiber proportion significantly improved glycemic control. On top of this, the insulin sensitivity (HOMA-IS) was significantly improved and may therefore directly improve the impact on long term complications. The disease specific formula should therefore be the preferred option to be used by diabetic and hyperglycemic patients in need of nutritional support.


Expression Level of Genes Coding for Cell Adhesion Molecules of Cadherin Group in Colorectal Cancer Patients.
Colorectal Cancer (CRC) is one of the most frequently diagnosed neoplasms and also one of the main death causes. Cell adhesion molecules are taking part in specific junctions, contributing to tissue integrality. Lower expression of the cadherins may be correlated with poorer differentiation of the CRC, and its more aggressive phenotype. The aim of the study is to designate the cadherin genes potentially useful for the diagnostics, prognostics, and the treatment of CRC. Specimens were collected from 28 persons (14 female and 14 male), who were operated for CRC. The molecular analysis was performed using oligonucleotide microarrays, mRNA used was collected from adenocarcinoma, and macroscopically healthy tissue. The results were validated using qRT-PCR technique. Agglomerative hierarchical clustering of normalized mRNA levels has shown 4 groups with statistically different gene expression. The control group was divided into 2 groups, the one was appropriate control (C1), the second (C2) had the genetic properties of the CRC, without pathological changes histologically and macroscopically. The other 2 groups were: LSC (Low stage cancer) and HSC (High stage cancer). Consolidated results of the fluorescency of all of the differential genes, designated two coding E-cadherin (CDH1) with the lower expression, and P-cadherin (CDH3) with higher expression in CRC tissue. The levels of genes expression are different for several groups of cadherins, and are related with the stage of CRC, therefore could be potentially the useful marker of the stage of the disease, also applicable in treatment and diagnostics of CRC.


Nanomechanical properties of TiO2 granular thin films.
Post-deposition annealing effects on nanomechanical properties of granular TiO2 films on soda-lime glass substrates were studied. In particular, the effects of Na diffusion on the films' mechanical properties were examined. TiO2 photocatalyst films, 330 nm thick, were prepared by dip-coating using a TiO2 sol, and were annealed between 100 °C and 500 °C. Film's morphology, physical and nanomechanical properties were characterized by atomic force microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, differential thermo-gravimetric analysis, and nanoindentation. Contrary to expectations, the maximum film hardness was achieved for 300°C annealing, with a value of 0.69±0.05 GPa. Higher annealing temperatures resulted in inferior mechanical properties. No pile-up or sink-in effects were observed with minimal creep for the 300 °C annealed sample. Considerable decrease in the amount of chemisorbed water was found with increasing annealing temperature, causing gel films densification, explaining the increasing trend of hardness with annealing temperature between 100 °C and 300 °C. DTA/TGA results also confirmed the weight loss and the endothermic reaction due to desorption of chemisorbed water. Decrease in hardness above 300 °C annealing is attributed to thermal diffusion of Na ions from the glass substrate, confirmed by nanoindentation tests on TiO2 films deposited on fused quartz, which did not exhibit hardness decrease after 300 °C annealing.


Transport of arginine and aspartic Acid into isolated barley mesophyll vacuoles.
The transport of arginine into isolated barley (Hordeum vulgare L.) mesophyll vacuoles was investigated. In the absence of ATP, arginine uptake was saturable with a K(m) of 0.3 to 0.4 millimolar. Positively charged amino acids inhibited arginine uptake, lysine being most potent with a K(i) of 1.2 millimolar. In the presence of free ATP, but not of its Mg-complex, uptake of arginine was drastically enhanced and a linear function of its concentration up to 16 millimolar. The nonhydrolyzable adenylyl imidodiphosphate, but no other nucleotide tested, could substitute for ATP. Therefore, it is suggested that this process does not require energy and does not involve the tonoplast ATPase. The ATP-dependent arginine uptake was strongly inhibited by p-chloromercuriphenylsulfonic acid. Furthermore, hydrophobic amino acids were inhibitory (I(50) phenylalanine 1 millimolar). Similar characteristics were observed for the uptake of aspartic acid. However, rates of ATP-stimulated aspartic acid transport were 10-fold lower as compared to arginine transport. Uptake of aspartate in the absence of ATP was negligible.


Calcium sensing receptor as a novel target for treatment of sepsis induced cardio-renal syndrome: Need for exploring mechanisms.
Calcium sensing receptor (CaSR) is localized in various organs and plays diverse physiological and pathological roles. Several scientific contributions have suggested the involvement of this cell surface receptor in cardiac and renal diseases. Sepsis is considered to be one of the major causes of ICU admissions. Cardiac dysfunction and acute kidney injury are major manifestations of sepsis and associated with reduced survival. Presently, the treatment approaches for management of sepsis induced cardiac depression and kidney injury are not satisfactory. Activation of CaSR has been demonstrated to induce cardiomyocyte damage upon lipopolysaccaharde (LPS) exposure by enhancing calcium ion levels, ROS (reactive oxygen species) production, promotion of inflammation and apoptosis. In addition, CaSR seems to be a critical regulator of intracellular calcium ion levels, which is directly implicated in induction of mitochondrial dysfunction and release of various pro-apoptotic pathways during sepsis. Certain evidences have also documented the expression of CaSR on neutrophils and T lymphocytes, where it is involved in activation of neutrophils and induces apoptosis of immune cells. Moreover, the expression of CaSR has been confirmed in podocytes, mesangial cells, proximal tubular cells and its activation is responsible for podocyte effacement, mesangial cell proliferation and proximal tubular cell apoptosis. We have analyzed the existing evidences, and critically discussed the possible mechanisms underlying CaSR activation mediated cardiac and renal dysfunction in sepsis condition.


Robot-assisted Gait Training Using Welwalk in Hemiparetic Stroke Patients: An Effectiveness Study with Matched Control.
Although studies on the efficacy of the rehabilitation robot are increasing, there are few reports using the robot for gait training in the actual clinical setting. This study aimed to investigate the effectiveness of gait training using Welwalk in hemiparetic stroke patients in a real clinical setting. This prospective study included 36 hemiparetic stroke patients who underwent gait training using Welwalk. We examined the walking ability improvement efficiency using Functional Independence Measure (FIM)-walk as the primary outcome, which was compared with that of 36 patients (matched control group) who underwent conventional rehabilitation. Other outcomes were the actual gait training period using Welwalk, raw FIM-walk score, lower extremity motor functions score in Stroke Impairment Assessment Set at discharge, and duration from stroke onset until discharge. The improvement efficiency of the FIM-walk was significantly higher in the Welwalk group than in the matched control group (control 0.48 ± 0.31, Welwalk 0.80 ± 0.38, p-value < 0.001). The mean gait training period using Welwalk was 5 weeks. No significant differences were found in other outcomes between the Welwalk group and the matched control group. This study demonstrated the effectiveness of gait training using Welwalk on the improvement efficiency of the FIM-walk in hemiparetic stroke patients in an actual clinical setting.


[A case of heparin-induced thrombocytopenia that worsened preexisting cerebral infarction].
A 75-year-old man was admitted to our hospital with dysesthesia of the right lip, dysphagia and gait disturbance. He presented with right Wallenberg syndrome and brain MR image showed a fresh infarction in the right lateral medulla. Therapy with heparin and ozagrel sodium was started. For a time his symptom improved a little, but after 8 days he developed re-infarction, thrombocytopenia and DIC, while being treated with heparin for cerebral infarction. Heparin was discontinued, and these symptoms improved quickly. The clinical course and the positive anti-platelet factor 4-heparin complex antibody suggested that these symptoms were caused by heparin-induced thrombocytopenia (HIT). HIT should be included as a differential diagnosis for progression of ischemic stroke under heparin therapy.


Pharyngolaryngeal morbidity with the laryngeal mask airway in spontaneously breathing patients: does size matter?
Currently, the manufacturer of the laryngeal mask airway (LMA; Laryngeal Mask Company, Ltd., Northfield End, Henley on Thames, Oxon, United Kingdom) recommends using as large a mask size as possible. The aim of this study was to compare the incidence of pharyngolaryngeal morbidity after the use of a large (size 5 in males and size 4 in females) or small (size 4 in males and size 3 in females) LMA in spontaneously breathing patients. A total of 258 male and female patients were randomly assigned to insertion of a large or small LMA while breathing spontaneously during general anesthesia. After insertion of the LMA, a "just-seal" cuff pressure was obtained, and intracuff pressure was measured at 10-min intervals until just before removal of the LMA. The 2- and 24-h incidence of postoperative sore throat, pain, hoarseness, dysphagia, and nausea and vomiting was assessed. Complications after LMA removal, including body movement, coughing, retching, regurgitation, vomiting, biting on the LMA, bronchospasm, laryngospasm, or the presence of blood on the LMA, were recorded. The use of a large LMA was associated with a higher incidence of sore throat in both sexes (20% vs. 7% in men, 21% vs. 5% in women; P < 0.05) and a higher incidence of hoarseness in male patients at 2 h postoperatively (21% vs. 9%, P < 0.05). There was a higher incidence of sore throat in male patients at 24 h postoperatively with the use of a large LMA (26% vs. 12%, P < 0.05). There was no difference in the incidence of complications of LMA removal orother pharyngolaryngeal morbidity, such as difficulty swallowing, drinking, and eating, or nausea and vomiting, between male or female groups at any time period with the use of a large LMA. Selection of a small laryngeal mask airway (size 4) in spontaneously breathing male patients may be more appropriate to limit the occurrence of sore throat on the first postoperative day. All patients had a fourfold increased risk of developing sore throat when a large LMA was used.


Electroacupuncture of Baihui and Shenting ameliorates cognitive deficits via Pten/Akt pathway in a rat cerebral ischemia injury model.
Cerebral ischemic stroke is a huge threat to the health and life of many people. Electroacupuncture (EA) at Baihui (GV20) and Shenting (GV24) acupoints can notably alleviate cerebral ischemia/reperfusion injury (CIRI). However, the molecular basis underlying the effectiveness of EA at the GV20 and GV24 acupoints for CIRI remains largely unknown. Our present study demonstrated that EA treatment at the GV20 and GV24 acupoints markedly alleviated middle cerebral artery occlusion/reperfusion (MCAO/R)-induced cognitive deficits and cerebral infarction in rats. Proteomics analysis revealed that 195 and 218 proteins were dysregulated in rat hippocampal tissues in the MCAO/R vs. sham group and thhhe EA vs. MCAO/R group, respectively. Moreover, 62 proteins with converse alteration trends in MCAO/R vs. sham and EA vs. MCAO/R groups were identified. These proteins might be implicated in the EA-mediated protective effect against MCAO/R-induced cerebral injury. GO enrichment analysis showed that 39 dysregulated proteins in the MCAO/R vs. sham group and 40 dysregulated proteins in the EA vs. MCAO/R group were related to brain and nerve development. Protein-protein interaction analysis of the abovementioned dysregulated proteins associated with brain and nerve development suggested that Pten/Akt pathway-related proteins might play major roles in regulating EA-mediated protective effects against MCAO/R-induced brain and nerve injury. Western blot assays demonstrated that Pak4, Akt3, and Efnb2 were expressed at low levels in the MCAO/R group vs. the sham group but at high levels in the EA group vs. the MCAO/R group. In conclusion, multiple proteins related to the protective effect of EA at the GV20 and GV24 acupoints against CIRI were identified in our study.


Growth Regulators Have Rapid Effects on Photosynthate Unloading from Seed Coats of Phaseolus vulgaris L.
Of nine plant growth regulators (indoleacetic acid, 1-naphthalene acetic acid, gibberellic acid, giberellin 4/7, 6-benzylaminopurine, 6-furfurylaminopurine, abscisic acid, and 1-aminocyclopropane carboxylic acid) tested, only 6-benzylaminopurine and abscisic acid affected (14)C-photosynthate unloading from excised seed coats of Phaseolus vulgaris L. Unloading, in the presence of KCl, was stimulated by 25 to 40%. Stimulation occurred immediately for 6-benzylaminopurine and for abscisic acid within 10 to 12 minutes of application.


Peripheral chemosensitivity is not blunted during 2 h of thermoneutral head out water immersion in healthy men and women.
Carbon dioxide (CO2) retention occurs during water immersion, but it is not known if peripheral chemosensitivity is altered during water immersion, which could contribute to CO2 retention. We tested the hypothesis that peripheral chemosensitivity to hypercapnia and hypoxia is blunted during 2 h of thermoneutral head out water immersion (HOWI) in healthy young adults. Peripheral chemosensitivity was assessed by the ventilatory, heart rate, and blood pressure responses to hypercapnia and hypoxia at baseline, 10, 60, 120 min, and post HOWI and a time-control visit (control). Subjects inhaled 1 breath of 13% CO2, 21% O2, and 66% N2 to test peripheral chemosensitivity to hypercapnia and 2-6 breaths of 100% N2 to test peripheral chemosensitivity to hypoxia. Each gas was administered four separate times at each time point. Partial pressure of end-tidal CO2 (PETCO2), arterial oxygen saturation (SpO2), ventilation, heart rate, and blood pressure were recorded continuously. Ventilation was higher during HOWI versus control at post (P = 0.037). PETCO2 was higher during HOWI versus control at 10 min (46 ± 2 vs. 44 ± 2 mmHg), 60 min (46 ± 2 vs. 44 ± 2 mmHg), and 120 min (46 ± 3 vs. 43 ± 3 mmHg) (all P < 0.001). Ventilatory (P = 0.898), heart rate (P = 0.760), and blood pressure (P = 0.092) responses to hypercapnia were not different during HOWI versus control at any time point. Ventilatory (P = 0.714), heart rate (P = 0.258), and blood pressure (P = 0.051) responses to hypoxia were not different during HOWI versus control at any time point. These data indicate that CO2 retention occurs during thermoneutral HOWI despite no changes in peripheral chemosensitivity.


Genetic Markers Associated with Power Athlete Status.
Athletic performance is a multifactorial phenotype influenced by environmental factors as well as multiple genetic variants. Different genetic elements have a great influence over components of athletic performance such as endurance, strength, power, flexibility, neuromuscular coordination, psychological traits and other features important in sport. The current literature review revealed that to date more than 69 genetic markers have been associated with power athlete status. For the purpose of the present review we have assigned all genetic markers described with reference to power athletes status to seven main groups: 1) markers associated with skeletal muscle structure and function, 2) markers involved in the inflammatory and repair reactions in skeletal muscle during and after exercise, 3) markers involved in blood pressure control, 4) markers involved in modulation of oxygen uptake, 5) markers that are regulators of energy metabolism and cellular homeostasis, 6) markers encoding factors that control gene expression by rearrangement of chromatin fibers and mRNA stability, and 7) markers modulating cellular signaling pathways. All data presented in the current review provide evidence to support the notion that human physical performance may be influenced by genetic profiles, especially in power sports. The current studies still represent only the first steps towards a better understanding of the genetic factors that influence power-related traits, so further analyses are necessary before implementation of research findings into practice.


Measurement of the uniaxial mechanical properties of rat brains infected by Plasmodium berghei ANKA.
Degenerative and demyelinating diseases are known to alter the mechanical properties of brain tissue. While few studies have characterized these biomechanical changes, it is clear that accurate characterization of the mechanical properties of diseased brain tissue could be a substantial asset to neuronavigation and surgery simulation through haptic devices. In this study, samples of brain tissue from rats infected with Plasmodium berghei ANKA, an African murine malaria parasite, are evaluated using a uniaxial tensile test machine. Infected brains having different levels of parasitemia are mounted on the testing machine and extended until failure of the tissue. The stress-strain curve of each sample is obtained and compared to healthy rat brain tissue. Young's modulus of each sample is extracted from the Hookean part of the stress-strain diagram. Young's modulus of rats' brain shows considerable difference among the samples having various levels of parasitemia compared with the controls. For instance, the brains with 0% (control), 1.5%, and 9% parasitemia showed a Young's modulus of 46.15, 54.54, and 266.67 kPa, respectively. This suggests sequestration of the stiffened and less deformable parasitized red blood cells in the brain microvasculature.


Acute, nongenomic effect of thyroid hormones in preventing calcium overload in newborn rat cardiocytes.
In this study, we examined the acute effects of thyroid hormones (TH) T(3) and T(4), leading to improvement of myocardial function through activation of Ca(2+) extrusion mechanisms and, consequently, prevention of intracellular calcium overload. Extracellular calcium elevation from 1.8 to 3.8 mM caused immediate increase in intracellular calcium level ([Ca(2+)](i)) in newborn cardiomyocyte cultures. Administration of 10 or 100 nM T(3) or T(4) rapidly (within 10 sec) decreased [Ca(2+)](i) to its control level. Similar results were obtained when [Ca(2+)](i) was elevated by decreasing extracellular Na(+) concentration, causing backward influx of Ca(2+) through Na(+)/Ca(2+) exchanger, or by administration of caffeine, releasing Ca(2+) from the sarcoplasmic reticulum (SR). Under these conditions, T(3) or T(4) decreased [Ca(2+)](i). T(3) and T(4) also exhibited protective effects during ischemia. T(3) or T(4) presence during hypoxia for 120 min in culture medium restricted the increase of [Ca(2+)](i) and prevented the pathological effects of its overload. An inhibitor of SR Ca(2+)-ATPase (SERCA2a), thapsigargin, increases [Ca(2+)](i) and in its presence neither T(3) nor T(4) had any effect on the [Ca(2+)](i) level. The reduction of [Ca(2+)](i) level by T(3) and T(4) was also blocked in the presence of H-89 (a PKA inhibitor), and by calmodulin inhibitors. The effect of TH on the reduction of [Ca(2+)](i) was prevented by propranolol, indicating that the hormones exert their effect through interaction with adrenergic receptors. These results support our hypothesis that TH prevent calcium overload in newborn rat cardiomyocytes, most likely by a direct, acute, and nongenomic effect on Ca(2+) transport into the SR.


Antiviral agents for ocular adenovirus infections.
Despite significant knowledge of the molecular biology and genetics of adenovirus, no specific antiviral agent has been developed for use in adenovirus infections. This contrasts with the situation in herpes simplex virus (HSV) and human immunodeficiency virus (HIV) infections, in which antiviral agents target specific enzymes. Antiviral agents active against HSV and interferons have been used in the treatment of ocular adenovirus infections with limited effect. Some newer nucleoside analogues have inhibitory activity against adenovirus in vitro and their effect is being assessed in newly developed animal models. Live vaccines have been used in both the United States and Canada to protect military recruits against adenovirus-induced respiratory disease. However, the inoculating strains are not normally associated with epidemic keratoconjunctivitis (EKC). There is a low prevalence of antibody against strains of adenovirus inducing EKC. Until such time as specific antiviral agents against adenovirus are developed, the mainstays of therapy will remain topical antibiotics to eliminate any secondary bacterial infection and topical steroids to suppress the immune response against adenovirus or adenovirus-infected cells. Neither form of treatment is adenovirus specific.


A Ruptured Anterior Communicating Artery Aneurysm with Infra-optic Course of the Anterior Cerebral Artery: A Case Report and a Short Review.
Infra-optic course of the anterior cerebral artery (IOA) is rare and approximately 55 cases of this anomaly have been described. We present a case of a ruptured anterior communicating artery (ACoA) aneurysm arising at the junction between the left IOA and the bilateral A2 segments, at which the right A1 segment was absent. One of the recurrent arteries of Heubner branched off directly from the aneurysmal dome, and was obstructed at aneurysmal neck clipping via an anterior interhemispheric (AIH) approach. In this report, accompanied anatomical variations and surgical approaches for ACoA aneurysms with IOA are reviewed. An IOA is frequently associated with other vascular anomalies, and the origin of functionally important recurrent arteries of Heubner is also variable. Preoperative accurate evaluation of vessel structures and the maximal exposure at surgery are very important. Pterional approach from the ipsilesional side is reportedly to be safe, but interhemispheric approach is also suggested to be effective as to full exposure to recognize the perianeurysmal anatomical structures including potential vessel anomalies.


Immunohistochemical correlation of steroid receptors and disease-free interval in 206 consecutive cases of breast cancer: validation of telequantification based on global scene segmentation.
Objective algorithms to evaluate immunocytochemistry in cytology and in histological sections are still under investigation. Clinical value, simplicity, robustness and adaptation to new technologies such as telemedicine and telequantification have to be taken into consideration. The present paper summarizes the experience of the immunoquantification of 206 cases diagnosed from 1990 to 1991, 36 clinical stage I cases, 110 stage II cases and 60 stage III cases. Initial clinical stage IV cases were excluded from the series. Quantification was done on frozen sections incubated with monoclonal estrogen and progesterone receptors (ER, PgR) by the peroxidase antiperoxidase (PAP) technique revealed with DAB. Automatic computerized measurements with a 550-nm filter were based on global scene segmentation, obtaining the parameters of percentage of positive area (pA) and immunoscore (ISC = sum i x pi), being the staining intensity (i) automatically evaluated in 5 grades multiple of the standard deviation (SD) of the control specimen (i x SD) stained with progressive haemathoxyline. Cut point of positive and negative specimens regarding ISC were obtained by semilogarithmic plot with biochemical receptor values (r = 0.73). The whole series showed a significant increase of negative specimens according to clinical stage and a higher number of PgR negative cases (44%) than ER negative cases (32%). The clinical relevance of the quantified parameters were evaluated by free interval disease survival curves being significant in the positive cutting point of ISC = 100 (ER P < 0.06; PgR P < 0.02) and the 40% negative area for the pA (ER P < 0.001; PgR P < 0.004). This quantification technique, which does not require individual cell segmentation, was reproducible at a distance (telequantification through high resolution videophones at 9600 bauds transmission rate; 55 cases). Coefficient of variation (CV) of the parameters in the original and transmitted cases were in the range of 0-5% in specimens with positive areas over 70%; less positive specimens require lower segmentation thresholds to get acceptable coefficients of variation. According to our results, immunohistochemical steroid receptor contents in breast cancer pathology, quantified by the technique of pixel integration, demonstrated the added value of the percentage of positive area in patient follow-up. Those having more than 40% of negative areas have recurrences mainly within the first year.


Effectiveness of five days of therapy with cefuroxime axetil suspension for treatment of acute otitis media.
In recent years there has been considerable interest in reducing the duration of antibiotic treatment regimens in patients with common bacterial infections. We conducted two independent, investigator-blinded, multicenter, randomized clinical trials, one of which included microbiologic evaluation of middle ear fluid obtained by tympanocentesis, comparing the efficacy and safety of 5 or 10 days of treatment with cefuroxime axetil suspension (CAE) with that of 10 days of treatment with amoxicillin/clavulanate suspension (AMX/CL) in children with acute otitis media. A total of 719 pediatric patients from the ages of 3 months to 12 years were enrolled in the 2 studies. Patients received CAE for either 5 or 10 days at 30 mg/kg/day in 2 divided doses (n = 242 and 235, respectively) or AMX/CL for 10 days at 40 mg/kg/day in 3 divided doses (n = 242). Patients in the CAE (5 days) group received placebo on Days 6 through 10. In the study that included tympanocentesis, bacteriologic assessments were based on middle ear fluid cultures obtained pretreatment and, when possible, after treatment in patients with an unsatisfactory clinical outcome. Organisms were isolated from the pretreatment middle ear fluid specimens of 177 of 244 (73%) patients undergoing tympanocentesis, with the primary pathogens being Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis (37, 35 and 12% of isolates, respectively). Pathogens were eradicated or presumed to be eradicated in 92% (24 of 26), 84% (32 of 38) and 95% (36 of 38) of bacteriologically evaluable patients treated with CAE for 5 or 10 days or with AMX/CL, respectively. A satisfactory clinical outcome (cure or improvement) occurred in 69% (101 of 147), 70% (121 of 173) and 74% (131 of 177) of clinically evaluable patients treated with CAE (5 days), CAE (10 days) or AMX/CL, respectively. Treatment with AMX/CL was associated with a significantly higher incidence of drug-related adverse events than was treatment with CAE for either 5 or 10 days (P < 0.001), primarily reflecting a higher incidence of drug-related gastrointestinal adverse events (34% vs. 17 and 12%, respectively; P < 0.001), particularly diarrhea. Treatment with CAE given twice daily for 5 days is equivalent to treatment for 10 days either with the same regimen of CAE or with AMX/CL given three times daily in pediatric patients with acute otitis media.


Pulmonary nocardiosis with bilateral diffuse granular lung shadows in a patient with subcutaneous panniculitic T-cell lymphoma.
A 40-year-old woman undergoing prednisolone and cyclosporine therapy for subcutaneous panniculitic T-cell lymphoma complained of a cough for a few weeks. A chest X-ray revealed bilateral diffuse granular shadows. Additionally, the patient was discovered to have multiple subcutaneous abscesses. Gram-stained smears of sputum and pus from the abscess showing branched gram-positive rods led to a diagnosis of pulmonary nocardiosis with dissemination to the lungs and subcutaneous tissues. Combination therapy consisting of sulfamethoxazole/trimethoprim and panipenem/betamipron produced rapid improvement of radiographic abnormalities. It is suggested that pulmonary nocardiosis should be considered in the differential diagnosis of diffuse granular shadows on chest X-rays, especially in immunocompromised patients.


Medicaid hospital spending: effects of reimbursement and utilization control policies.
Numerous Medicaid hospital spending policies were developed following the passage of the 1981 Omnibus Budget Reconciliation Act. The impact of reimbursement and utilization control policies on Medicaid hospital spending was measured using Medicaid program data for 1977-84. Medicaid prospective reimbursement was found to contain real hospital spending by controlling spending per recipient. However, sustained reductions in the growth in real Medicaid spending are achieved only when Medicaid is included in a broader regulatory framework, not when it is the sole regulated payer. Prior authorization for specific services reduces growth in hospital spending by reducing the growth in inpatient recipients.


Evaluation of prognostic markers for canine mast cell tumors treated with vinblastine and prednisone.
Canine cutaneous mast cell tumor (MCT) is a common neoplastic disease associated with a variable biologic behavior. Surgery remains the primary treatment for canine MCT; however, radiation therapy (RT) and chemotherapy are commonly used to treat aggressive MCT. The goals of this study were to evaluate the prognostic utility of histologic grade, c-KIT mutations, KIT staining patterns, and the proliferation markers Ki67 and AgNORs in dogs postoperatively treated with vinblastine and prednisone +/- RT, and to compare the outcome of dogs treated with post-operative chemotherapy +/- RT to that of a prognostically matched group treated with surgery alone. Associations between prognostic markers and survival were evaluated. Disease-free intervals (DFI) and overall survival times (OS) of dogs with similar pretreatment prognostic indices postoperatively treated with chemotherapy were compared to dogs treated with surgery alone. Histologic grade 3 MCTs, MCTs with c-KIT mutations, MCTs with increased cytoplasmic KIT, and MCTs with increased Ki67 and AgNOR values were associated with decreased DFI and OS. Dogs with histologic grade 3 MCT had significantly increased DFI and OS when treated with chemotherapy vs. surgery alone. Although not statistically significant due to small sample sizes, MCTs with c-KIT mutations had increased DFI and OS when treated with chemotherapy vs. surgery alone. This study confirms the prognostic value of histologic grade, c-KIT mutations, KIT staining patterns, and proliferation analyses for canine MCT. Additionally, the results of this study further define the benefit of postoperative vinblastine and prednisone for histologic grade 3 MCTs.


The effect of combination anti-endothelial growth factor receptor and anti-vascular endothelial growth factor receptor 2 targeted therapy on lymph node metastasis: a study in an orthotopic nude mouse model of squamous cell carcinoma of the oral tongue.
To evaluate the therapeutic effect of treatment with a combination of the monoclonal antibodies to the vascular endothelial growth factor receptor (DC101) and the epidermal growth factor receptor (cetuximab) in an orthotopic nude mouse model of metastatic squamous cell carcinoma of the oral tongue (SCCOT). In vivo study. A translational research laboratory at a comprehensive cancer center. Male athymic nude mice aged 8 to 12 weeks. To develop orthotopic nude mouse models of SCCOT, OSC-19 cells or luciferase (Luc)-expressing OSC-19-Luc and JMAR-Luc cells were injected into the tongues of nude mice. Animals were randomly divided into 4 groups: DC101 alone, cetuximab alone, DC101 plus cetuximab, or placebo, and all treatments were administered twice per week for 4 weeks. The in vivo antitumor activity was monitored noninvasively by bioluminescence imaging. Tumors were resected at necropsy, and immunohistochemical and immunofluorescent staining were performed. Tumor size, bioluminescence, animal survival, and percentage of animals with lymph node metastasis. At the conclusion of the treatment period, the mean tumor volumes in the cetuximab alone and the DC101 plus cetuximab groups had decreased significantly compared with those that received the placebo control (68% [P = .002] and 84% [P < .001], respectively). Significant effects of the treatment were also observed in bioluminescence imaging. Mice treated with DC101 plus cetuximab also lived longer and had a lower incidence of neck lymph node metastases compared with the control group (P = .003). Treatment with DC101 plus cetuximab inhibited the growth of SCCOT and decreased the incidence of the neck lymph node metastases in vivo. These results suggest that this combination treatment may be an effective strategy against metastatic SCCOT and warrants further preclinical trials.


[Possibilities of resistance prediction to neoadjuvant concomitant chemoradiotherapy in the treatment algorithm of patients with rectal carcinoma].
Neoadjuvant concomitant chemoradiotherapy has become a standard treatment of locally advanced rectal adenocarcinomas (LARA). It leads to shrinkage of the tumor mass and subsequently to an increase in complete resections (R0 resections), increasing a feasibility of sphincter-sparing intervention avoiding colostomy. It is based on concurrent application of fluoropyrimidines (5-fluorouracil, capecitabine) and radiotherapy (45 - 50,4 Gy). It shows less acute toxicity and improves local control rate in comparison to adjuvant treatment. Unfortunately, neoadjuvant chemoradiotherapy is not beneficial for all patients. The treatment response ranges from a complete pathological remission (pCR, ypT0ypN0) to a resistance. It is reported that cca 15 percent of patients with advanced rectal cancer show pCR which is indicative of improved long-term prognosis. The following is a review of the significance of neoadjuvant concomitant chemoradiotherapy in the treatment algorithm of patients with LARA and summary of potentional clinical-pathological and molecular markers of response prediction to neoadjuvant therapy. The most important clinical studies concern serum tumor markers levels, clinical lymph node classification. The components of the carcinogenic pathways are explored, including oncogenes, tumor supressor genes, microsatellite instability (MSI) and potentional markers involved in apoptosis, angiogionesis, proliferation as well as metastasis and invasion, are reviewed. Finally, the role of specific enzymes associated with the metabolism of fluoropyrimidines are examined. No one marker has been consistently identified as clinically applicable. Studies designed to determine the potentional markers are hampered by various techniques as well as tumor heterogenity and recent scientific approach--studying individual molecular markers. Gene expression profiling analysis of multiple genes from the same tumor is becoming reality. We suppose that this assessment will lead in future in finding combination of markers for predicting prognosis and response to therapy in rectal cancer.


Ethylene formation in rat liver microsomes.
Reduced triphosphopyridine nucleotide and pyrophosphate-dependent peroxidation of lipids in rat liver microsomes were coupled to the generation of ethylene in the presence of cuprous ions. This system suggests a model for the biogenesis of ethylene in cells.


Automatic hierarchy classification in venation networks using directional morphological filtering for hierarchical structure traits extraction.
The extraction of vein traits from venation networks is of great significance to the development of a variety of research fields, such as evolutionary biology. However, traditional studies normally target to the extraction of reticulate structure traits (ReSTs), which is not sufficient enough to distinguish the difference between vein orders. For hierarchical structure traits (HiSTs), only a few tools have made attempts with human assistance, and obviously are not practical for large-scale traits extraction. Thus, there is a necessity to develop the method of automated vein hierarchy classification, raising a new challenge yet to be addressed. We propose a novel vein hierarchy classification method based on directional morphological filtering to automatically classify vein orders. Different from traditional methods, our method classify vein orders from highly dense venation networks for the extraction of traits with ecological significance. To the best of our knowledge, this is the first attempt to automatically classify vein hierarchy. To evaluate the performance of our method, we prepare a soybean transmission image dataset (STID) composed of 1200 soybean leaf images and the vein orders of these leaves are manually coarsely annotated by experts as ground truth. We apply our method to classify vein orders of each leaf in the dataset. Compared with ground truth, the proposed method achieves great performance, while the average deviation on major vein is less than 5 pixels and the average completeness on second-order veins reaches 54.28%.


A fluorescent probe for monitoring nitric oxide production using a novel detection concept.
A fluorescent probe using a novel 'spin exchange' concept was developed for monitoring nitric oxide (NO) production. The probe is composed of 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) labeled with acridine and N-dithiocarboxysarcosine (DTCS)-Fe(II) complex. When the non-fluorescent acridine-TEMPO was incubated with DTCS-Fe(II) complex in buffer solution, the nitroxide radical in the acridine-TEMPO interacted with the Fe(II) through a redox interaction. This interaction recovered the fluorescence based on the acridine moiety. The addition of an NO-releasing reagent caused a fluorescent decrease of the probe due to the irreversible binding of NO to the Fe(II), and the amount of the fluorescent decrease strictly corresponded to that of released NO. Using this probe, less than 100 nM of NO can be detected. This probe system is not only useful for monitoring direct production of NO in an aqueous solution, but is also interesting as a basic concept by which to construct new types of NO fluorescent probes.


Revealing the hidden diversity of marine fungi in Portugal with the description of two novel species, Neoascochyta fuci sp. nov. and Paraconiothyrium salinum sp. nov.
Fungi are ubiquitous organisms with a wide distribution in almost all ecosystems, including marine environments. Coastal and estuarine ecosystems remain poorly unexplored as fungal habitats, potentially harbouring a hidden diversity with important ecological roles. During an extensive survey of marine fungi in coastal and estuarine Portuguese environments, a collection of 612 isolates was obtained from water, algae, sponges and driftwood. From these, 282 representative isolates were selected through microsatellite-primed PCR (MSP-PCR) fingerprinting analysis, which were identified based on DNA sequence data. The collection yielded 117 taxa from 38 distinct genera, which were identified using DNA sequence analysis. Overall, fungal community composition varied with host/substrate, but the most abundant taxa in the collection were Cladosporium cladosporioides, Penicillium terrigenum, Penicillium brevicompactum and Fusarium equiseti/incarnatum complex. The occurrence of a high fungal diversity harbouring novel species was disclosed. Through a multilocus phylogeny based on ITS, tub2 and tef1-α sequences, in conjunction with morphological and physiological data, we propose Neoascochyta fuci sp. nov. and Paraconiothyrium salinum sp. nov.


Oxidation of Gallium-based Liquid Metal Alloys by Water.
Gallium alloys with other low melting point metals, such as indium or tin, to form room-temperature liquid eutectic systems. The gallium in the alloys rapidly forms a thin surface oxide when exposed to ambient oxygen. This surface oxide has been previously exploited for self-stabilization of liquid metal nanoparticles, retention of metastable shapes, and imparting stimuli-responsive behavior to the alloy surface. In this work, we study the effect of water as an oxidant and its role in defining the alloy surface chemistry. We identify several pathways that can lead to the formation of gallium oxide hydroxide (GaOOH) crystallites, which may be undesirable in many applications. Furthermore, we find that some crystallite formation pathways can be reinforced by typical top-down particle synthesis techniques like sonication. This improved understanding of interfacial interactions provides critical insight for process design and implementation of advanced devices that utilize the unique coupling of flexibility and conductivity offered by these gallium-based liquid metal alloys.


Membrane lipid and expression responses of Saccharolobus islandicus REY15A to acid and cold stress.
Archaea adjust the number of cyclopentane rings in their glycerol dibiphytanyl glycerol tetraether (GDGT) membrane lipids as a homeostatic response to environmental stressors such as temperature, pH, and energy availability shifts. However, archaeal expression patterns that correspond with changes in GDGT composition are less understood. Here we characterize the acid and cold stress responses of the thermoacidophilic crenarchaeon Saccharolobus islandicus REY15A using growth rates, core GDGT lipid profiles, transcriptomics and proteomics. We show that both stressors result in impaired growth, lower average GDGT cyclization, and differences in gene and protein expression. Transcription data revealed differential expression of the GDGT ring synthase grsB in response to both acid stress and cold stress. Although the GDGT ring synthase encoded by grsB forms highly cyclized GDGTs with ≥5 ring moieties, S. islandicus grsB upregulation under acidic pH conditions did not correspond with increased abundances of highly cyclized GDGTs. Our observations highlight the inability to predict GDGT changes from transcription data alone. Broader analysis of transcriptomic data revealed that S. islandicus differentially expresses many of the same transcripts in response to both acid and cold stress. These included upregulation of several biosynthetic pathways and downregulation of oxidative phosphorylation and motility. Transcript responses specific to either of the two stressors tested here included upregulation of genes related to proton pumping and molecular turnover in acid stress conditions and upregulation of transposases in cold stress conditions. Overall, our study provides a comprehensive understanding of the GDGT modifications and differential expression characteristic of the acid stress and cold stress responses in S. islandicus.


[Liver abscesses successfully treated by intraportal administration of amphotericin B in a case of acute myeloblastic leukemia (M2)].
A 46-year-old male was admitted to our hospital because of relapse of acute myeloblastic leukemia (M2). Remission was successfully reinduced after reinduction chemotherapy consisting of daunorubicin, cytosine arabinoside, etoposide and vincristine, but was complicated by neutropenia. After the therapy, the patient had persistent fever of about 38 degrees C despite broad-spectrum antibiotics therapy and the patient developed pain in the right quadrant of the abdomen. The white blood cell count rose to 23000/mm3. Liver function tests showed abnormal findings mainly consisting of an elevated serum alkaline phosphatase level. Ultrasonography showed multiple hypoechoic lesions in the liver and CT scans also revealed multiple low density areas. Therefore he was suspected of having a complication of liver abscesses. Amphotericin B was administered 75 mg/day intravenously every other day. A percutaneous liver biopsy was performed, but was not diagnostic. Blood cultures were negative for pathogens. Amphotericin B was administered up to a cumulative dosage of 2.3 g, but the patient remained febrile. Then he had an exploratory laparotomy and an open liver biopsy. The liver biopsy samples showed fungal elements proved by PAS staining. A catheter was inserted into the portal vein. Administration of Amphotericin B was started 20 mg daily through the catheter. The temperature fell to normal after institution of this therapy. The abnormal findings in CT scans almost disappeared and the inflammatory findings became negative after he had received intraportal administration of Amphotericin B over three months. Through the analysis of this case study, we confirmed that the intraportal administration of Amphotericin B was effective to the intractable liver abscesses due to fungi.


Nighttime Sleep Awakening Frequency and Its Consistency Predict Future Academic Performance in College Students.
Although the relationship between sleep and academic performance has been extensively examined, how sleep predicts future academic performance (e.g., 2-3 years) remains to be further investigated. Using wearable smartwatches and a self-report questionnaire, we tracked sleep activities of 45 college students over a period of approximately half a month to see whether their sleep activities predicted their academic performance, which was estimated by grade point average (GPA). Results showed that both nighttime sleep awakening frequency and its consistency in the tracking period were not significantly correlated with the GPA for the courses taken in the sleep tracking semester (current GPA). However, both nighttime sleep awakening frequency and its consistency inversely predicted the GPA for the rest of the courses taken after that semester (future GPA). Moreover, students with more difficulty staying awake throughout the day obtained lower current and future GPAs, and students with higher inconsistency of sleep quality obtained lower future GPA. Together, these findings highlight the importance of nighttime sleep awakening frequency and consistency in predicting future academic performance, and emphasize the necessity of assessing the consistency of sleep measures in future studies.


Preparation of Graphene-Perfluoroalkoxy Composite and Thermal and Mechanical Properties.
Perfluoroalkoxy (PFA) material exhibits perfect corrosion resistance under both acid or alkaline circumstances; thus, steel heat exchangers are being substituted by those made of PFA in high corrosion atmospheres. However, the low thermal conductivity of PFA degrades its heat transfer efficiency. Based on the extremely high heat conductivity of graphene, a novel grapheme-PFA composite was proposed to simultaneously meet the demands of heat transfer and corrosion resistance. Ultrasonic dispersion technology was used to disperse the aggregated graphene in the composite. Graphene⁻PFA composites with different graphene contents and using different dispersing solvents were prepared with a hot pressing method, and thermal conductivity, abrasion resistance, crystallization and pyrolysis properties were investigated. The thermal conductivity of PFA composites with graphene content of 20 wt % reached 5.017 W (m·k)-1, which is 21.88 times that of pure PFA. The relationship between the abrasion loss and the friction coefficient of the composites with different graphene contents was obtained. A thermogravimetric analyzer was used to investigate the crystallization and pyrolysis behavior of the composites; correspondingly, the temperature range that composites work in was determined. The heat conduction mechanism was analyzed through the thermal conductivity model of composite materials. The composite material is expected to play an important role in the development of high-performance thermal equipment.


Lack of association between variations in the melanocortin 5 receptor gene and bipolar disorder.
The melanocortin 5 receptor gene maps to the bipolar susceptibility locus on chromosome 18p11.2. Given the biological role of melanocortins and their influence on the hypothalamic-pituitary-adrenal axis, the melanocortin 5 receptor gene is a plausible candidate gene for bipolar disorder. We tested the hypothesis that the potential functional variation Phe209Leu confers susceptibility to bipolar disorder in a case-control study. Genotypes for two variations in the coding region and one variation approximately 7 kb upstream from the coding region were obtained from 345 unrelated bipolar I patients and 275 control samples. Genotypes and allele frequencies were compared between groups using chi(2) contingency analysis. Allele frequencies of the Phe209Leu polymorphism did not differ significantly between bipolar patients and controls (P=0.679). Allele frequencies of the C744T and the intergenic A/G polymorphism did not differ significantly between bipolar patients and controls. All variations were in strong linkage disequilibrium. Variations in the melanocortin 5 receptor gene are unlikely to confer susceptibility to bipolar disorder in this sample. Further studies are required to elucidate the susceptibility locus for bipolar disorder on chromosome 18p11.


Long-term outcomes among antiretroviral-naive human immunodeficiency virus-infected patients with small increases in CD4+ cell counts after successful virologic suppression.
To evaluate the frequency and predictive factors of discordant immune response, we performed a prospective cohort study of 288 antiretroviral-naive human immunodeficiency virus (HIV)-infected patients who initiated highly active antiretroviral therapy (HAART) and maintained complete virus suppression for > or =24 months. The median CD4+ cell count was 186x10(6) cells/L, and the median HIV RNA level was 5 log(10) copies/mL. After 24 months of therapy, 42 (16.5%) of 255 patients had a median CD4+ cell count increase of <100x10(6) cells/L. By logistic regression analysis, previous injection drug use was associated with a CD4+ cell count increase of <100x10(6) cells/L (risk ratio [RR], 2.326; 95% confidence interval [CI], 1.077-5.023; P=.032); inclusion of a protease inhibitor (PI) in the HAART regimen reduced the risk of poor immunologic recovery (RR, 0.160; 95% CI, 0.061-0.417; P<.001). Failure of the CD4+ cell count to increase was relatively common among antiretroviral-naive patients in the year after the initiation of HAART and the achievement of complete virus suppression. PI-containing regimens provided better immunologic response.


Laparoscopic donor nephrectomy in Hawaii.
Laparoscopic donor nephrectomy for transplant is a minimally invasive, effective, and safe operation that also provides less post-operative pain and earlier return to pre-donation activity. In review of the first 10 cases, no major complications occurred and mean hospital stay was 3.7 days. All recipients of these kidneys displayed excellent allograft function (mean creatinine--1.5 mg/dL) and no ureteral problems. Successful use of this procedure has also resulted in a steady increase in the number of living transplants performed in Hawaii and perhaps this will impact the 330 patients currently awaiting renal transplant.


Orthogonal polarization spectral imaging as a tool for the assessment of hepatic microcirculation: a validation study.
Quantitative analysis of liver microcirculation using intravital fluorescence microscopy in animals has increased our knowledge about ischemia-reperfusion injury. However, because of the size of the instrumentation and the necessity of fluochromes for contrast enhancement, human liver microcirculation cannot be observed. Orthogonal Polarization Spectral (OPS) imaging is a recently introduced technique that can be used to visualize the microcirculation without the need for fluorescent dyes. It is a small, hand-held device and could potentially be used to study the microcirculation of the human liver in a clinical setting. However, before implementation into clinical use its ability to quantitatively measure microcirculatory parameters must be validated. The livers of Spraque-Dawley rats (n=9) were exteriorized, and images were obtained using OPS imaging and intravital fluorescence microscopy of the identical microvascular regions before and after the induction of a 20-min warm lobar ischemia. Images were videotaped for later computer-assisted off-line analysis. OPS imaging can be used to accurately quantify the sinusoidal perfusion rate, vessel diameter, and venular red blood cell velocity. Correlation parameters were significant and Bland-Altman analyses showed good agreement for data obtained from the two methods at baseline as well as during reperfusion. OPS imaging can be used to quantitatively measure microcirculatory parameters in the rat liver under both physiological and pathophysiological conditions. Thus, OPS imaging has the potential to be used to make quantitative measurements of the microcirculation in the human liver.


Dopamine increases lung liquid clearance during mechanical ventilation.
Short-term mechanical ventilation with high tidal volume (HVT) causes mild to moderate lung injury and impairs active Na+ transport and lung liquid clearance in rats. Dopamine (DA) enhances active Na+ transport in normal rat lungs by increasing Na+-K+-ATPase activity in the alveolar epithelium. We examined whether DA would increase alveolar fluid reabsorption in rats ventilated with HVT for 40 min compared with those ventilated with low tidal volume (LVT) and with nonventilated rats. Similar to previous reports, HVT ventilation decreased alveolar fluid reabsorption by ~50% (P < 0.001). DA increased alveolar fluid reabsorption in nonventilated control rats (by ~60%), LVT ventilated rats (by approximately 55%), and HVT ventilated rats (by ~200%). In parallel studies, DA increased Na+-K+-ATPase activity in cultured rat alveolar epithelial type II cells (ATII). Depolymerization of cellular microtubules by colchicine inhibited the effect of DA on HVT ventilated rats as well as on Na+-K+-ATPase activity in ATII cells. Neither DA nor colchicine affected the short-term Na+-K+-ATPase alpha1- and beta1-subunit mRNA steady-state levels or total alpha1- and beta1-subunit protein abundance in ATII cells. Thus we reason that DA improved alveolar fluid reabsorption in rats ventilated with HVT by upregulating the Na+-K+-ATPase function in alveolar epithelial cells.


Surface-mount sapphire interferometric temperature sensor.
A fiber-optic high-temperature sensor is demonstrated by bonding a 45 degrees -polished single-crystal sapphire fiber on the surface of a sapphire wafer, whose optical thickness is temperature dependent and measured by white-light interferometry. A novel adhesive-free coupling between the silica and sapphire fibers is achieved by fusion splicing, and its performance is characterized. The sensor's interference signal is investigated for its dependence on angular alignment between the fiber and the wafer. A prototype sensor is tested to 1,170 degrees C with a resolution of 0.4 degrees C, demonstrating excellent potential for high-temperature measurement.


Basic color categories and Mandarin Chinese color terms.
Basic color terms used in Mandarin Chinese have been controversial since first discussed by Berlin and Kay in 1969. Previous studies showed much inconsistency on what should be considered as basic color terms in Mandarin Chinese. In the present study, we investigated categories of color rather than merely the color terms used by Taiwanese native Mandarin speakers. Using samples conforming to the Berlin and Kay survey, various colors were chosen from a collection of Natural Color System (NCS) colored papers and mounted on a piece of neutral gray card. The card was then mounted on a touch-screen, under D65 illumination. Thirty-two single-character color related Mandarin terms were selected from a Chinese character database according to frequency of use. Participants were required to select the color sample that matched the term by pressing a virtual button on the touch screen. The results show that certain terms can be directly correlated to basic color terms in English, comparable with the results of Berlin and Kay's original study and those that followed. However, some terms, such as Mo ( ink), Tie ( iron), and Cai (vegetable), show a wide spread of term maps and inconsistent use among subjects. Principle component analysis (PCA) procedures were used to analysis the commodity of data among subjects. The findings suggest that the basic color categories among Mandarin Chinese speakers are similar to those found in the World Color Survey (WCS), but are represented by wide-spread and inconsistent color terms among speakers.


Personality disorder and early therapeutic alliance in two time-limited therapies.
This study examined the relationship of pre-treatment personality disorder diagnosis to the quality of early therapeutic alliance in 145 patients randomly assigned to either cognitive behavioral therapy or brief relational therapy. The pre-treatment diagnosis was established by DSM-IV (SCID) and Wisconsin Personality Inventory. Quality of the alliance was assessed by patient and therapist reports using the 12-item Working Alliance Inventory, Session Evaluation Questionnaire, and direct questions of ruptures. Results indicated that pre-treatment personality disorder as determined by SCID predicted no variables of early psychotherapy process. Factor scores yielded from a PCA of the WISPI indicated that high impulsivity, dysregulation, and lability were associated with lower patient and therapist ratings of session depth of exploration and higher patient ratings of rupture intensity.


Genetic analysis of the accumulation of COR14 proteins in wild (Hordeum spontaneum) and cultivated (Hordeum vulgare) barley.
The cold-regulated (COR14) protein of 14 kDa is a polypeptide accumulated under low-temperature conditions in the chloroplasts of barley leaves. In H. vulgare the COR14 antibody cross-reacts with two proteins, with a slightly different relative molecular weight around the marker of 14.4 kDa, referred to as COR14a and COR14b (high and low relative molecular weight, respectively). In a collection of H. spontaneum genotypes a clear polymorphism was found for the corresponding COR proteins. While some accessions showed the same COR pattern as cultivated barley, in 38 out of 61 accessions examined the COR14 antibody cross-reacted with an additional coldregulated protein with a relative molecular weight of about 24 kDa (COR24). The accumulation of COR24 was often associated with the absence of COR14b; the relationship between the COR14b/COR24 polymorphism and the adaptation of H. spontaneum to different environments is discussed. By studying COR14 accumulation in cultivated barley we have found that the threshold induction-temperature of COR14a is associated with the loci controlling winter hardiness. This association was demonstrated by using either a set of 30 cultivars of different origin, or two sets of frost-tolerant and frost-sensitive F1 doubled-haploid lines derived from the cross Dicktoo (winter type) x Morex (spring type). These results suggest that the threshold induction-temperature of COR14a can be a potential biochemical marker for the identification of superior frostresistant barley genotypes.


The Streptococcus gordonii surface proteins GspB and Hsa mediate binding to sialylated carbohydrate epitopes on the platelet membrane glycoprotein Ibalpha.
Platelet binding by Streptococcus gordonii strain M99 is dependent on expression of the cell wall-anchored glycoprotein GspB. This large cell surface protein is exported from the M99 cytoplasm via a dedicated transport system that includes SecA2 and SecY2. GspB is highly similar to Hsa, a protein expressed by S. gordonii Challis that has been characterized as a sialic acid binding hemagglutinin. In this study, we compared the contribution of GspB and Hsa to the adherence of S. gordonii to selected glycoproteins. Our results indicate that GspB can mediate binding to a variety of sialylated glycoproteins. GspB facilitates binding to carbohydrates bearing sialic acid in either alpha(2-3) or alpha(2-6) linkages, with a slight preference for alpha(2-3) linkages. Furthermore, GspB readily mediates binding to sialic acid residues on immobilized glycocalicin, the extracellular portion of the platelet membrane glycoprotein (GP) Ibalpha (the ligand binding subunit of the platelet von Willebrand factor receptor complex GPIb-IX-V). Although Hsa is required for the binding of S. gordonii Challis to sialic acid, most of the Hsa expressed by Challis is retained in the cytoplasm. The deficiency in export is due, at least in part, to a nonsense mutation in secA2. Hsa export can be enhanced by complementation with secA2 from M99, which also results in significantly greater binding to sialylated glycoproteins, including glycocalicin. The combined results indicate that GspB and Hsa contribute similar binding capabilities to M99 and Challis, respectively, but there may be subtle differences in the preferred epitopes to which these adhesins bind.


[Priority analysis for controlling endocrine disrupting chemicals in municipal wastewater treatment plants of China].
Ecological risk quotients and estradiol equivalent concentrations of 32 endocrine disrupting chemicals (EDCs) in 4 categories were calculated and analyzed using reported concentrations in secondary effluents from municipal wastewater treatment plants in China, considering both extreme scenario for maximum concentration and moderate scenario for median concentration. These EDCs include industrial chemicals, pesticides, natural estrogens, and pharmaceuticals. In extreme scenario, 12 chemicals of ecological risk and 9 chemicals of estrogenicity were identified. While in moderate scenario, 6 chemicals of ecological risk and 5 chemicals of estrogenicity were identified. After further scoring and ranking, 4 priority EDCs have been suggested for control in municipal wastewater treatment plants in China, including 17a-ethynylestradiol, estrone, nonylphenol, and bisphenol A.


Efficient implementation of the Shack-Hartmann centroid extraction for edge computing.
Adaptive optics (AO) is an established technique to measure and compensate for optical aberrations. One of its key components is the wavefront sensor (WFS), which is typically a Shack-Hartmann sensor (SH) capturing an image related to the aberrated wavefront. We propose an efficient implementation of the SH-WFS centroid extraction algorithm, tailored for edge computing. In the edge-computing paradigm, the data are elaborated close to the source (i.e., at the edge) through low-power embedded architectures, in which CPU computing elements are combined with heterogeneous accelerators (e.g., GPUs, field-programmable gate arrays). Since the control loop latency must be minimized to compensate for the wavefront aberration temporal dynamics, we propose an optimized algorithm that takes advantage of the unified CPU/GPU memory of recent low-power embedded architectures. Experimental results show that the centroid extraction latency obtained over spot images up to 700×700 pixels wide is smaller than 2 ms. Therefore, our approach meets the temporal requirements of small- to medium-sized AO systems, which are equipped with deformable mirrors having tens of actuators.


Systematic Review of Intervention Studies Aiming at Reducing Inequality in Dental Caries among Children.
(1) Background: The objective is to systematically review the evidence on intervention programs aiming at reducing inequality in dental caries among children. (2) Methods: Two independent investigators searched MEDLINE, Cochrane library, and Ovid up to December 2020 to identify intervention studies assessing the impact on socioeconomic inequalities in dental caries among children. The interventions included any health promotion/preventive intervention aiming at reducing caries among children across different socioeconomic groups. Comparison groups included children with alternative or no intervention. Cochrane criteria were used to assess interventional studies for risk of bias. (3) Results: After removal of duplicate studies, 1235 articles were retained. Out of 43 relevant papers, 13 articles were identified and used in qualitative synthesis, and reported quantifiable outcomes. The included studies varied in measurements of interventions, sample size, age groups, and follow-up time. Five studies assessed oral health promotion or health-education, four assessed topical fluorides, and four assessed water fluoridation. Interventions targeting the whole population showed a consistent reduction of socioeconomic inequalities in dental caries among children. (4) Conclusion: The quality of included papers was moderate. High heterogeneity did not allow aggregation of the findings. The overall findings suggest that whole population interventions such as water fluoridation are more likely to reduce inequalities in children's caries than target population and individual interventions.


Nanoparticle-mediated targeting of MAPK signaling predisposes tumor to chemotherapy.
The MAPK signal transduction cascade is dysregulated in a majority of human tumors. Here we report that a nanoparticle-mediated targeting of this pathway can optimize cancer chemotherapy. We engineered nanoparticles from a unique hexadentate-polyD,L-lactic acid-co-glycolic acid polymer chemically conjugated to PD98059, a selective MAPK inhibitor. The nanoparticles are taken up by cancer cells through endocytosis and demonstrate sustained release of the active agent, resulting in the inhibition of phosphorylation of downstream extracellular signal regulated kinase. We demonstrate that nanoparticle-mediated targeting of MAPK inhibits the proliferation of melanoma and lung carcinoma cells and induces apoptosis in vitro. Administration of the PD98059-nanoparticles in melanoma-bearing mice inhibits tumor growth and enhances the antitumor efficacy of cisplatin chemotherapy. Our study shows the nanoparticle-mediated delivery of signal transduction inhibitors can emerge as a unique paradigm in cancer chemotherapy.


Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis.
To identify groups of people with RA with different disability trajectories over 10 years, despite comparable levels of inflammation. Data for this analysis came from three European prospective cohort studies of people with RA [Norfolk Arthritis Register (NOAR), Early RA Network (ERAN), Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR)]. Participants were assessed regularly over 8 (ERAN) to 10 (NOAR/ESPOIR) years. Inclusion criteria were: recruited after 1 January 2000, <24 months baseline symptom duration, and disability (HAQ) and inflammation [two-component DAS28 (DAS28-2C)] recorded at baseline and at one other follow-up. People in each cohort also completed patient-reported outcome measures at each assessment (pain, fatigue, depressive symptoms). Group-based trajectory models were used to identify distinct groups of people with similar HAQ and DAS28-2C trajectories over follow-up. This analysis included 2500 people with RA (NOAR: 1000, ESPOIR: 766, ERAN: 734). ESPOIR included more women and the participants were younger [mean (standard deviation) age: NOAR: 57.1 (14.6), ESPOIR: 47.6 (12.5), ERAN: 56.8 (13.8); women: NOAR: 63.9%, ESPOIR: 76.9%, ERAN: 69.1%). Within each cohort, two pairs of trajectories following the hypothesized pattern (comparable DAS28-2Cs but different HAQs) were identified. Higher pain, fatigue and depressive symptoms were associated with increased odds of being in the high HAQ trajectories. Excess disability is persistent in RA. Controlling inflammation may not be sufficient to alleviate disability in all people with RA, and effective pain, fatigue and mood management may be needed in some groups to improve long-term function.


Labyrinthitis ossificans: histopathologic consideration for cochlear implantation.
Labyrinthitis ossificans may be a hindrance to cochlear implantation by making electrode insertion difficult. We performed a histopathologic study of 24 temporal bones with labyrinthitis ossificans from multiple causes. The organ of Corti was graphically reconstructed and the degree of obstruction was estimated for each millimeter of the cochlea. Correlations were calculated between the degree of new bone formation and the cause, patient's age and sex, and time from the original temporal bone insult. Our results demonstrate that complete cochlear ossification is rare. The scala tympani in the basal turn of the cochlea is the most frequent area of ossification, regardless of the cause of the labyrinthitis ossificans. Meningogenic labyrinthitis, usually a childhood disease, was associated with the greatest amount of ossification. When ossification resulted from tympanogenic labyrinthitis, the scala tympani was completely ossified near the round window niche in all temporal bones. Neo-ossification of the basal turn associated with otosclerosis was limited to the proximal 6 mm of the scala tympani in all cases. Three temporal bones had a patent round window niche and basal turn, but significant apical and middle-turn ossification. Peripheral sensorineural elements were severely degenerated in the region of the ossification in all specimens, and spiral ganglion cell counts were decreased.


Altered antigenic profiling and infectivity of Porphyromonas gingivalis in smokers and non-smokers with periodontitis.
Cigarette smokers are more susceptible to periodontal diseases and are more likely to be infected with Porphyromonas gingivalis than non-smokers. Furthermore, smoking is known to alter the expression of P. gingivalis surface components and compromise immunoglobulin (Ig)G generation. The aim of this study is to evaluate whether the overall IgG response to P. gingivalis is suppressed in smokers in vivo and whether previously established in vitro tobacco-induced phenotypic P. gingivalis changes would be reflected in vivo. The authors examined the humoral response to several P. gingivalis strains as well as specific tobacco-regulated outer membrane proteins (FimA and RagB) by enzyme-linked immunosorbent assay in biochemically validated (salivary cotinine) smokers and non-smokers with chronic periodontitis (CP: n = 13) or aggressive periodontitis (AgP: n = 20). The local and systemic presence of P. gingivalis DNA was also monitored by polymerase chain reaction. Smoking was associated with decreased total IgG responses against clinical (10512, 5607, and 10208C; all P <0.05) but not laboratory (ATCC 33277, W83) P. gingivalis strains. Smoking did not influence IgG produced against specific cell-surface proteins, although a non-significant pattern toward increased total FimA-specific IgG in patients with CP, but not AgP, was observed. Seropositive smokers were more likely to be infected orally and systemically with P. gingivalis (P <0.001), as determined by 16S RNA analysis. Smoking alters the humoral response against P. gingivalis and may increase P. gingivalis infectivity, strengthening the evidence that mechanisms of periodontal disease progression in smokers may differ from those of non-smokers with the same disease classification.


The beginnings of photometry.
A brief account of the beginnings of photometry, with emphasis on some of the early attempts to quantify light that preceded the actual invention of useful photometers, is presented.


Centrifugo-pneumatic valve for metering of highly wetting liquids on centrifugal microfluidic platforms.
We designed and experimentally validated a new type of passive valve for centrifugal microfluidic platforms. A liquid column entering an unvented receiving chamber is stopped by the counter-pressure of compressed air. This valve opens under defined conditions at high centrifugal frequencies at which the interface between liquid and air becomes unstable and enables a phase exchange, forwarding the liquid. Burst frequencies of the valve were determined for liquids typically used in biochemical assays: pure water, water with detergent concentrations between 0.01 and 10%, and pure ethanol. Burst frequencies between 8.5 +/- 0.6 and 27.9 +/- 2.0 Hz were measured for different surface tensions. The burst frequencies can be tuned by simple geometrical changes in the valving structure. The valve does not require ultra-precise structures or local surface modifications and is therefore ideal for low-cost microfluidic polymer disks. Potential applications are in the field of multiparameter and panel analysis, such as PCR-genotyping.


Mature brain-derived neurotrophic factor and its receptor TrkB are upregulated in human glioma tissues.
There are two forms of brain-derived neurotrophic factor (BDNF), precursor of BDNF (proBDNF) and mature BDNF, which each exert opposing effects through two different transmembrane receptor signaling systems, consisting of p75 neurotrophin receptor (p75NTR) and tyrosine receptor kinase B (TrkB). Previous studies have demonstrated that proBDNF promotes cell death and inhibits the growth and migration of C6 glioma cells through p75NTR in vitro, while mature BDNF has opposite effects on C6 glioma cells. It is hypothesized that mature BDNF is essential in the development of malignancy in gliomas. However, histological data obtained in previous studies were unable distinguish mature BDNF from proBDNF due to the lack of specific antibodies. The present study investigated the expression of mature BDNF using a specific sheep monoclonal anti-mature BDNF antibody in 42 human glioma tissues of different grades and 10 control tissues. The correlation between mature BDNF and TrkB was analyzed. Mature BDNF expression was significantly increased in high-grade gliomas, and was positively correlated with the malignancy of the tumor and TrkB receptor expression. The present data have demonstrated that increased levels of mature BDNF contribute markedly to the development of malignancy of human gliomas through the primary BDNF receptor TrkB.


Genotype-phenotype correlations in a large series of patients with muscle type CPT II deficiency.
The adult or 'muscular' form of carnitine-palmitoyl-transferase II (CPT II) deficiency presents with recurrent rhabdomyolytic episodes and myoglobinuria, usually triggered by prolonged exercise. The aim of this study was to investigate a large series of patients in order to provide genotype-phenotype correlations. Our muscle tissue bank was surveyed for patients showing attacks of rhabdomyolysis with myoglobinuria. After exclusion of cases affected with toxic myoglobinuria, McArdle's disease and Becker muscular dystrophy, over 100 patients were selected for isotope-exchange radioenzymatic assay of CPT enzyme activity in muscle, and 25 cases resulted to be defective. Acylcarnitine profile was performed in five patients using tandem mass spectrometry. Mutations in the CPT2 gene were identified using DNA sequencing. Although the clinical features were rather homogeneous, some patients presented life-threatening events (acute renal failure) and muscle weakness, and low levels of residual CPT activity. The typical acylcarnitine profile found in mutant patients confirmed its value as a screening method for further diagnostic investigations. We found a high frequency of the common p.Ser113Leu mutation, the recurrence of the rare p.Arg631Cys mutation in a genetic isolate in Southern Italy, and identified four novel mutations. In some affected patients only one mutant allele was found, suggesting either incomplete mutation detection or the possibility they are symptomatic carriers. Null mutations and homozygous mutations were frequently associated with a more severe phenotype and biochemical defect. The identification of symptomatic obligate heterozygous carriers might suggest that additional epigenetic or environmental factors may contribute to determine the phenotype.


Selective reductive transformations using samarium diiodide-water.
Samarium diiodide (SmI(2)) is one of the most important reductive electron transfer reagents available in the laboratory. Key to the popularity of SmI(2) is the ability of additives and co-solvents to tune the properties of the reagent. Over the last decade water has emerged as a particularly valuable additive, opening up new chemical space and leading to the discovery of unprecedented selectivity and new reactions promoted by SmI(2). In this Feature Article we review recent progress in the application of SmI(2)-H(2)O systems, with an emphasis on mechanistic considerations and the development of new transformations.


Phase I trial of topotecan in combination with gemcitabine in refractory solid tumor patients.
To determine maximum tolerated dose (MTD) and evidence of antitumor activity of topotecan in combination with gemcitabine in refractory cancer patients. This was a Phase I, prospective, dose-escalation trial that employed a novel-dosing schema to investigate clinical safety. Patients were treated in six cohorts with topotecan (T)+gemcitabine (G). The doses of T and G were administered by 30-minute IV infusion, T on days one through five (0.3 mg/m2 to 1 mg/m2) and G on days one and 15 of a 28-day cycle (1000 mg/m2 to 1500 mg/m2). Toxicity was monitored. Twenty-three cancer patients were enrolled (colorectal, n=5; lung, n=4; gastric, n=4; esophageal, n=2; other, n=8). Two of three patients developed grade 3 nonhematologic toxicity attributed to study regimen, thereby fulfilling dose limiting toxicity requirements at cohort 6 (T, 1 mg/m2, G, 1500 mg/m2). Maximum tolerated dose (MTD) was established at cohort 5 (T, 1 mg/m2, G, 1250 mg/m2). Ten patients were treated at cohort 5. Nonhematologic adverse effects (AEs) >grade 3 attributed to the study regimen were not observed. Hematologic toxicity was frequent. Twenty-five percent of patients in cohort 2 and 50% of patients in cohorts 4, 5, and 6 had a reduction of ANC to <500 mm3. All neutropenic episodes were less than one week in duration. Five of the patients in the last three cohorts required delay and/or dose-reduction of G. Nineteen of 23 enrolled patients were evaluable for response. Two patients achieved a minimal response. The MTD was observed at a T dose of 1 mg/m2 administered on days 1 through 15, and a G dose of 1250 mg/m2 administered on days 1 and 15 via 30 minute intravenous (IV) infusion.


Challenges and prospects of high-voltage aqueous electrolytes for energy storage applications.
Aqueous electrolytes have attracted widespread attention as they are safe, environmentally benign and cost effective, holding great promise for future low-cost and sustainable energy storage devices. Nonetheless, the narrow electrochemical stability window caused by water electrolysis, as well as the trade-off between the stability window and other properties remain the bottleneck problem for the practical applications of aqueous electrolytes. Deep insights into the correlations between the microscopic physicochemical and electrochemical mechanisms and the macroscopic properties of aqueous electrolyte are essential for the envisaged applications, yet a systematic analysis of the recent progress in this area is still lacking. In this Perspective article, the basic mechanisms and influencing factors of water electrolysis including the hydrogen evolution and oxygen evolution reactions is critically examined. We systematically review the current state-of-the-art on high-voltage aqueous electrolytes focusing on the fundamental mechanisms of ion kinetics leading to dynamic electrolyte restructuring. Recent advances on the optimization of high-voltage aqueous electrolytes are also summarized. The existing challenges are identified and perspectives for exploring and developing future high-voltage aqueous electrolytes are provided.


Persistence Enhancement of a Promising Tick Repellent, Benzyl Isothiocyanate, by Yeast Microcarriers.
Phenethyl isothiocyanate isolated from Armoracia rusticana root oil and its derivatives were tested at different doses in a bioassay designed to evaluate repellency against individual Haemaphysalis longicornis nymphs. Among the tested compounds, benzyl isothiocyanate exhibited repellency against H. longicornis nymphs at the lowest dose of 0.00625 mg/cm2, followed by phenethyl isothiocyanate (0.0125 mg/cm2) and phenyl isothiocyanate (0.025 mg/cm2). The behavioral responses of H. longicornis nymphs exposed to benzyl isothiocyanate and phenethyl isothiocyanate indicated that the mode of action of these compounds can be mainly attributed to the vapor phase. Encapsulated benzyl isothiocyanate showed repellency up to 120 min post-application at 0.1 mg/cm2, whereas pure benzyl isothiocyanate showed repellency up to 60 min post-application at 0.1 mg/cm2. The present study suggests that benzyl isothiocyanate is a potential repellent for protection against H. longicornis nymphs, and encapsulation in yeast cells may enhance the repellency effect.


Clinical significance of palliative care assessment in patients referred for urgent intensive care unit admission: A cohort study.
To evaluate clinical characteristics of patients with palliative care (PC) and urgent intensive care unit (ICU) referrals in the same hospital admission. All urgent ICU referrals at an academic, tertiary hospital, and the co-occurrence and timing of PC assessment were retrieved from a prospectively collected database. From May 2014 to May 2015, 2476 patients were analyzed and 179 (7%) had co-occurrence of PC assessment and urgent ICU referral in the same hospital admission. Hospital mortality was higher (odds ratio, 8.3; 95% confidence interval, 5.4-12.7) and ICU admission was lower (odds ratio, 0.54; 95% confidence interval, 0.40-0.74) in patients with PC assessment, compared with patients without concurrent PC and ICU referrals. Variables associated with PC assessment were older age, diagnosis of cancer, depressed level of consciousness, nonsurgical admission, lower performance status, physician's subjective prognosis of poor outcome, and length of hospitalization before ICU referral. In this cohort of patients with urgent ICU referral, clinical characteristics at the moment of ICU referral were associated with co-occurrence of PC assessment in the same hospital admission. These characteristics might guide the development of instruments to enhance early referral of high-risk patients to PC services.


Fluxes of h and k in corn roots : characterization and stoichiometries using ion-selective microelectrodes.
We report here on an experimental system that utilizes ion-selective microelectrodes to measure the electrochemical potential gradients for H(+) and K(+) ions within the unstirred layer near the root surface of both intact 4-day-old corn seedlings and corn root segments. Analysis of the steady state H(+) and K(+) electrochemical potential gradients provided a simultaneous measure of the fluxes crossing a localized region of the root surface. Net K(+) influx values obtained by this method were compared with unidirectional K(+) ((86)Rb(+)) influx kinetic data; at any particular K(+) concentration, similar values were obtained by either technique. The ionspecific microelectrode system was then used to investigate the association between net H(+) efflux and net K(+) influx. Although the computed H(+):K(+) stoichiometry is dependent upon the choice of diffusion coefficients, the values obtained were extremely variable, and net K(+) influx rarely appeared to be charge-balanced by H(+) efflux. In contrast to earlier studies, we found the cortical membrane potential to be highly K(+) sensitive within the micromolar K(+) concentration range. Simultaneous measurements of membrane potential and K(+) influx, as a function of K(+) concentration, revealed similar K(m) values for the depolarization of the potential (K(m) 6-9 micromolar K(+)) and net K(+) influx (K(m) 4-7 micromolar K(+)). These data suggest that K(+) may enter corn roots via a K(+)-H(+) cotransport system rather than a K(+)/H(+) antiporter.