Medical treatment or surgical intervention? A cooperative retrospective study on infective endocarditis--timing of operation.
Two hundred and five patients treated for infective endocarditis over the last 10 years were reviewed. There were 185 cases of native valve endocarditis (NVE) and 20 of prosthetic valve endocarditis (PVE). In the NVE group there were 175 clinically active patients and 10 non-active patients. The mortalities among 108 non-surgical and 57 surgical patients were 15.7% and 14.0%, respectively. Leading causes of deaths in the former were cardiac failure, embolism and cerebral hemorrhage. Patients with embolism showed significantly higher mortality. Culture negative endocarditis resulted in almost the same incidence of hospital death and urgent operation as staphylococcal endocarditis, and a higher incidence than streptococcal endocarditis. In 9 of 33 patients operated at our hospital, surgery was performed on an urgent basis and one NYHA class IV patient died. Indications for operation were intractable cardiac failure, uncontrollable infection and angina. In the PVE group, 3 of 4 patients operated in the active stage died of severe cardiac failure generated preoperatively. The only survivor was a patient operated early under stable hemodynamics. These results suggest that culture negative endocarditis should be observed as closely as staphylococcal endocarditis and early operation should be considered for patients with progressive cardiac failure, embolism and uncontrollable infection.


Multiphoton microscopy and fluorescence lifetime imaging provide a novel method in studying drug distribution and metabolism in the rat liver in vivo.
Multiphoton microscopy has been shown to be a useful tool in studying drug distribution in biological tissues. In addition, fluorescence lifetime imaging provides information about the structure and dynamics of fluorophores based on their fluorescence lifetimes. Fluorescein, a commonly used fluorescent probe, is metabolized within liver cells to fluorescein mono-glucuronide, which is also fluorescent. Fluorescein and its glucuronide have similar excitation and emission spectra, but different fluorescence lifetimes. In this study, we employed multiphoton fluorescence lifetime imaging to study the distribution and metabolism of fluorescein and its metabolite in vivo in rat liver. Fluorescence lifetime values in vitro were used to interpret in vivo data. Our results show that the mean fluorescence lifetimes of fluorescein and its metabolite decrease over time after injection of fluorescein in three different regions of the liver. In conclusion, we have demonstrated a novel method to study a fluorescent compound and metabolite in vivo using multiphoton fluorescence lifetime imaging.


Restrictions on the inversion of the fresnel reflectance equations.
The regions for which the Fresnel equations can be inverted to determine the optical constants, n and K, from polarized reflection measurements of a plane electromagnetic wave are presented for different angles of incidence. The surface upon which this wave is incident is assumed to be a large, smooth, planar surface of a conducting medium that is linear, homogeneous, and isotropic. The sensitivity of the inversion procedure to +/-1% error in the measured reflectances is presented graphically. Such a small error in reflectances could produce a large error, more than 20%, in the determined optical constants n and K with K being the more erroneous. Angles of incidence in the neighborhood of 10 degrees and 80 degrees produce the largest acceptable regions for inversion.


Model evaluation using electroencephalography and magnetoencephalography.
The source of both the measured visual evoked potentials and the measured visual evoked magnetic fields was estimated by means of an inverse procedure. The model used consisted of a single current dipole positioned in a volume conductor consisting of four concentric spheres. Comparison of the results showed that the estimations did not always match. In order to reveal a possible cause of this mismatch a realistically shaped multicompartment model of the head was constructed. From forward simulations it followed that the influence of the realistic shape was apparent, especially when the dipole was positioned deep within the brains.


Dynamics of bone marrow-derived endothelial progenitor cell/mesenchymal stem cell interaction in co-culture and its implications in angiogenesis.
Tissue engineering aims to regenerate tissues and organs by using cell and biomaterial-based approaches. One of the current challenges in the field is to promote proper vascularization in the implant to prevent cell death and promote host integration. Bone marrow endothelial progenitor cells (BM-EPCs) and mesenchymal stem cells (MSCs) are bone marrow resident stem cells widely employed for proangiogenic applications. In vivo, they are likely to interact frequently both in the bone marrow and at sites of injury. In this study, the physical and biochemical interactions between BM-EPCs and MSCs in an in vitro co-culture system were investigated to further clarify their roles in vascularization. BM-EPC/MSC co-cultures established close cell-cell contacts soon after seeding and self-assembled to form elongated structures at 3days. Besides direct contact, cells also exhibited vesicle transport phenomena. When co-cultured in Matrigel, tube formation was greatly enhanced even in serum-starved, growth factor free medium. Both MSCs and BM-EPCs contributed to these tubes. However, cell proliferation was greatly reduced in co-culture and morphological differences were observed. Gene expression and cluster analysis for wide panel of angiogenesis-related transcripts demonstrated up-regulation of angiogenic markers but down-regulation of many other cytokines. These data suggest that cross-talk occurs in between BM-EPCs and MSCs through paracrine and direct cell contact mechanisms leading to modulation of the angiogenic response.


An inhibition enzyme immunoassay using a human monoclonal antibody (K14) reactive with gp41 of HIV-1 for the serology of HIV-1 infections.
An inhibition enzyme immunoassay (IEIA), using a human monoclonal antibody (K14) reactive with gp41 of HIV-1, was evaluated for its applicability to the serology of HIV-1 infections. Using panels of serum samples from seronegative and confirmed HIV-1-seropositive individuals, it was shown that all the HIV-1-positive samples in a panel from The Netherlands and 97% of the HIV-1-positive samples from Tanzania were identified by this IEIA. Six per cent of the IEIA-positive samples from Tanzania could not be confirmed in other assays. Testing of serial dilutions of serum samples from African individuals with confirmed HIV-1, HIV-2 or HIV(ANI70) infections in the K14 IEIA, indicated that a HIV-1-specific assay based on this principle may be developed.


Signatures of prelocalized states in classically chaotic systems.
We investigate the statistics of eigenfunction intensities P(/psi/(2)) in dynamical systems with classical chaotic diffusion. Our results contradict some recent theoretical considerations that challenge the applicability of field theoretical predictions, derived in a different framework for diffusive disordered samples. For two-dimensional systems, the tails of P(/psi/(2)) contradict the results of the optimal fluctuation method, but agree very well with the predictions of the nonlinear sigma model.


[Expression and clinical significance of MTDH, HIF-1α and TKTL1 in laryngeal carcinoma].
To investigate the functional mechanism of metadherin (MTDH), hypoxia-inducible factor-1 alpha (HIF-1α) and transketolase-like gene 1 (TKTL1) and their interaction with each other in laryngeal carcinoma development. Thirty laryngeal carcinoma samples and 20 samples of para-carcinoma tissue were taken from the patients received operation treatment. The expression levels of MTDH, HIF-1α and TKTL1 were detected in all the samples by SP immunohistochemical methods. The data were analyzed by the SPSS13.0 statistical software. The positive expression rate of MTDH, HIF-1α and TKTL1 in the 30 cases of laryngeal carcinoma was 56.67%, 60.00% and 63.33%, respectively, which was 20.00%,10.00% and 15.00% respectively in the para-carcinoma tissue, the difference of the positive expression rate of the tested objects between these two groups was statistically significant (P < 0.05 or P < 0.01). Of the 30 cases of laryngeal carcinoma, the positive expression rate of MTDH, HIF-1α and TKTL1 in the cases with lymphnode metastasis was 84.62%, 84.62% and 79.62%, respectively, compared with the rate in those without lymph nodes metastasis, which was 35.29%, 41.18% and 35.29%. The difference of the positive expression rate of the tested objects between these two groups was statistically significant (P < 0.05). In the tissue of poorly differentiated squamons cell carcinoma verified by pathology, the positive expression rates of MTDH and HIF-1α was 73.68% and 84.21%, respectively, while that in the tissue of well differentiated squamous carcinoma was 27.27% and 18.18%. The difference of the positive expression rate of the tested objects between these two groups was statistically significant (P < 0.05 or (P < 0.01). The positive expression rate of TKTL1 in laryngeal carcinoma at stage I-II was 25.00% and that at stage III-IV was 72.22%, the difference between which was statistically significant (P < 0.05). The positive expression rate of HIF-1α in laryngeal carcinoma at stage I-II was 33.33% and that at stage III-IV was 77. 78%, the difference between which was statistically significant (P < 0.05). The expression of MTDH, HIF-1α and TKTL1 showed no relationship with age,smoking amount or the tumor location (P > 0.05). The Spearman's rank correlation analysis showed that the positive expression rates of MTDH and HIF-1α in laryngeal carcinoma had positive correlation (r = 0.384, P < 0.05); the positive expression rates of TKTL1 and HIF-1α in laryngeal carcinoma had positive correlation (r = 0.508, P < 0.01); But there was no significant correlation between the positive expression rates of MTDH and TKTL1 in laryngeal carcinoma (r = -0.107, P > 0.05). It suggested that these three proteins may have close relationship with the occurrence, invasion and metastasis of the laryngeal carcinoma. MTDH and TKTL1 may be expected to be new clinical targets for laryngeal carcinoma treatment and it could offer theoretical basis for the prognosis of the laryngeal carcinoma.


The size and curvature of anionic covesicle substrate affects the catalytic action of cytosolic phospholipase A2.
Cytosolic phospholipase A2 (cPLA2) is normally located in the cytosol, but in response to cellular activation the enzyme binds to the membrane at the lipid/water interface where it catalyzes the hydrolysis of the sn-2 ester of arachidonate-containing phospholipids. Synthetic phospholipid vesicle systems have been used in kinetic and mechanistic analyses of cPLA2, but these systems result in a rapid loss of enzyme activity. In the present research, covesicles of 1,2-dimyristoyl-sn-glycero-3-phosphomethanol (DMPM) containing </=10 mol% 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) as substrate were used to show that this premature cessation of enzyme-catalyzed hydrolysis is dependent on vesicle size with 25-nm-diameter vesicles supporting little activity as compared to 100-, 200-, and 400-nm vesicles. This suggests that the curvature of the vesicle may shift a conformational equilibrium toward an enzyme state which does not support activity. Interestingly, the presence of 30% (v/v) glycerol greatly enhanced the activity of the enzyme, although vesicle size-dependent premature cessation of hydrolysis was still observed. While the premature cessation of hydrolysis in the absence of glycerol is accompanied by enzyme inactivation, little inactivation occured in the presence of glycerol, indicating that premature cessation and inactivation are not absolutely coupled. When using this covesicle substrate system under conditions (6-10 mM CaCl2) where the vesicles are fusing, no premature cessation of hydrolysis has been observed. This is despite a mean vesicle diameter of 400-450 nm under vesicle-fusing conditions, which is comparable to the largest vesicles used under nonfusing conditions (0.5 mM CaCl2) where considerable premature cessation of hydrolysis was observed. Since DMPM has an intrinsic active site dissociation constant at least 330 times larger than that of PAPC, the optimum conditions for conducting kinetic and mechanistic analyses of cPLA2 with this covesicle substrate is one in which cPLA2 is assayed in the presence of glycerol and with fusion-inducing concentrations of calcium. The use of 1,2-dioleoyl-sn-glycero-3-phosphomethanol (DOPM) instead of DMPM in this system supports much less activity and adds the complication of a strong affinity of DOPM for the active site.


[Is the damaging action of catecholamines on the myocardium realized via hyperstimulation of the beta receptors?].
Experiments on an isolated rat heart were made to compare the damaging action on the myocardium of catecholamines (noradrenaline, adrenaline and isoproterenol) differing in the affinity for beta-receptors. The damage to myocardial cells was evaluated from the release into the perfusate of intracellular enzymes (creatine phosphokinase and lactate dehydrogenase) and the number of contracture damaged myocytes. Noradrenaline exerted the most powerful damaging action on the myocardium at a concentration of 10(-6) M. Perfusion of the heart with isoproterenol at concentrations of 10(-6) M and 10(-5) M did not lead to the affection of cardiomyocytes. It was isoproterenol concentration exceeding noradrenaline concentration 100 times that produced an increase in the rate of the release of the enzymes to the perfusate and a rise of the number of contractures in the myocardium, with the above increase being less than that provoked by adrenaline and noradrenaline (10(-6) M). It is concluded that the mechanism of the cardiotoxic effect of catecholamines cannot be reduced only to their effect on myocardial beta-receptors.


The heterogeneity of regional specific ventilation is unchanged following heavy exercise in athletes.
Heavy exercise increases ventilation-perfusion mismatch and decreases pulmonary gas exchange efficiency. Previous work using magnetic resonance imaging (MRI) arterial spin labeling in athletes has shown that, after 45 min of heavy exercise, the spatial heterogeneity of pulmonary blood flow was increased in recovery. We hypothesized that the heterogeneity of regional specific ventilation (SV, the local tidal volume over functional residual capacity ratio) would also be increased following sustained exercise, consistent with the previously documented changes in blood flow heterogeneity. Trained subjects (n = 6, maximal O2 consumption = 61 ± 7 ml·kg(-1)·min(-1)) cycled 45 min at their individually determined ventilatory threshold. Oxygen-enhanced MRI was used to quantify SV in a sagittal slice of the right lung in supine posture pre- (preexercise) and 15- and 60-min postexercise. Arterial spin labeling was used to measure pulmonary blood flow in the same slice bracketing the SV measures. Heterogeneity of SV and blood flow were quantified by relative dispersion (RD = SD/mean). The alveolar-arterial oxygen difference was increased during exercise, 23.3 ± 5.3 Torr, compared with rest, 6.3 ± 3.7 Torr, indicating a gas exchange impairment during exercise. No significant change in RD of SV was seen after exercise: preexercise 0.78 ± 0.15, 15 min postexercise 0.81 ± 0.13, 60 min postexercise 0.78 ± 0.08 (P = 0.5). The RD of blood flow increased significantly postexercise: preexercise 1.00 ± 0.12, 15 min postexercise 1.15 ± 0.10, 45 min postexercise 1.10 ± 0.10, 60 min postexercise 1.19 ± 0.11, 90 min postexercise 1.11 ± 0.12 (P < 0.005). The lack of a significant change in RD of SV postexercise, despite an increase in the RD of blood flow, suggests that airways may be less susceptible to the effects of exercise than blood vessels.


Protein Tyrosine Phosphatase 4A3 (PTP4A3) Promotes Human Uveal Melanoma Aggressiveness Through Membrane Accumulation of Matrix Metalloproteinase 14 (MMP14).
To study PTP4A3 phosphatase and MMP14 metalloprotease synergy in uveal melanoma aggressiveness. Cell membrane localization of matrix metalloprotease 14 (MMP14) in uveal melanoma cells expressing protein tyrosine phosphatase A3 (PTP4A3) was assessed by flow cytometry or immunohistochemistry. The vesicular trafficking of MMP14 in the presence of PTP4A3 was evaluated in OCM-1 cells expressing either the wild-type or mutated phosphatase. Finally, MMP14 localization at the cell membrane of OCM-1 cells was impaired using RNA interference, and the PTP4A3-related migration in vitro and invasiveness in vivo of the treated cells were evaluated. We found that the membrane-anchored MMP14 is enriched at the cell surface of OCM-1 cells, patient-derived xenograft cells, and human primary uveal melanoma tumors expressing PTP4A3. Moreover, we show that PTP4A3 and MMP14 colocalize and that the vesicular trafficking of MMP14 is faster in the presence of active PTP4A3. Finally, we demonstrate that inhibition of MMP14 expression in uveal melanoma cells expressing PTP4A3 impairs their migration in vitro and invasiveness in vivo. Our observations indicate that PTP4A3 increases cell membrane accumulation of MMP14 as a result of increased cellular trafficking of the metalloprotease. We also show that downregulation of MMP14 expression reduced PTP4A3-induced cell migration and invasiveness. Taken together, our findings suggest that PTP4A3-related subcellular localization of MMP14 is an important event in metastasis induction.


Clinical characteristics and prognosis of ground-glass opacity nodules in young patients.
The detection rate of ground-glass opacity (GGO) in young patients has increased year by year with the increasingly widespread use of high-resolution computed tomography (HRCT) and the increased resolution of HRCT imaging. However, no scholars have reported the clinical characteristics and prognosis of GGO in young patients systematically. The purpose of this study is to investigate the clinical characteristics and prognosis presenting as GGO in young patients. Clinical data of 127 young patients who were diagnosed as GGO and who underwent video-assisted thoracoscopic surgery (VATS) and had routine pathological examination were collected from January 2016 to January 2017. Nodules were classified according to benign and malignant: 26 benign nodules (Group A) and 115 malignant nodules (Group B). The pathological types, nodules size, surgical methods were analyzed, and the clinical characteristics and prognosis were evaluated. The results of pathological examination of 91 pure ground-glass opacities (pGGOs) revealed 16 adenocarcinoma in situs (AISs), 42 micro invasive adenocarcinomas (MIAs), 13 invasive adenocarcinomas (IAs), 8 atypical adenomatous hyperplasias (AAHs), 1 inflammatory granuloma, 2 pulmonary inflammatory pseudotumors (IPTs) and 9 other benign nodules. The results of pathological examination of 50 mixed ground-glass opacities (mGGOs) revealed 6 AISs, 29 MIAs, 9 IAs, 1 AAH, 2 inflammatory granulomas and 3 other benign nodules. All patients had no lymph nodes invasion. The rates of perioperative complications were 6.30%, compared to 7.63% for long-term complications. None of the patients with GGO experienced a recurrence and death [2-year recurrence-free survival (RFS), 100%; 2-year overall survival (OS), 100%]. The GGO in young patients that received VATS has a high proportion of malignant, its prognosis is satisfied.


Bortezomib in combination with rituximab, dexamethasone, ifosfamide, cisplatin and etoposide chemoimmunotherapy in patients with relapsed and primary refractory diffuse large B-cell lymphoma.
Patients with relapsed or refractory diffuse large B-cell lymphoma may experience extended survival with second-line chemotherapy and autologous stem cell transplant (ASCT). Since a major determinant of outcome after ASCT is responsiveness to second-line therapy, the development of more effective second-line treatments is desirable. We investigated the addition of bortezomib to rituximab, dexamethasone, ifosfamide, cisplatin and etoposide (VIPER). Fifteen patients were enrolled, of whom seven were refractory to first-line chemotherapy and only three had maintained first response for 1 year. Nine (60%) patients achieved objective responses, of which three (20%) were IWC-PET (International Workshop Criteria positron emission tomography) complete responses. Median progression-free survival was 3 months, and median overall survival was 10 months. At a median follow-up of 26 months, five patients (33%) remained alive. Treatment was well tolerated with no unexpected toxicity. Although response rates did not meet predefined criteria, activity was at least comparable to other second-line approaches despite a poor-prognosis patient population.


[Effects of proton pump inhibitor on airway hyperresponsiveness in asthmatics with gastroesophageal reflux].
Previous data suggest the high incidence of gastroesophageal reflux (GER) in asthmatics, although the relationship between GER and the respiratory condition in asthmatics remain unclear. We investigated the incidence of GER in asthmatics and the association between the effects of proton-pump inhibitor (PPI) on respiratory functions and esophageal pH in asthmatics with GER. Two hundreds ninety outpatients who attended our unit with asthma received GER symptoms questionnaire used at Mayo Clinic. Twenty three of them who answered to have any GER symptom were treated with PPI (lansoprazole 30 mg/day) for eight weeks, and investigated changes in the GER symptoms and peak expiratory flow rates (PEFR) before and after treatment. Furthermore, in six of twenty three, airway hyperresponsiveness to methacholine and esophageal pH monitor for 24 hours were measured in order to evaluate the association between esophageal pH and the effect of PPI on GER during the test. Furthermore, the serum level of theophylline was analyzed for assessment of the PPI effect on theophylline metabolism. 150 of 290 asthmatics had answered to have any GER symptom including cough. Most of GER symptoms had improved except for cough after treatment with PPI. The airway hyperresponsiveness significantly improved after treatment with PPI (n=6, p<0.03), although PEF and FEV1 were not significantly changed. These results suggest that PPI may be an effective drug for asthmatics with GER through suppression of airway hyperresponsiveness.


A novel small molecular weight compound with a carbazole structure that demonstrates potent human immunodeficiency virus type-1 integrase inhibitory activity.
The integration of reverse transcribed proviral DNA into a host genome is an essential event in the human immunodeficiency virus type 1 (HIV-1) replication life cycle. Therefore, the viral enzyme integrase (IN), which plays a crucial role in the integration event, has been an attractive target of anti-retroviral drugs. Several IN inhibitory compounds have been reported previously, yet none has been successful in clinical use. To find a new, more successful IN inhibitor, we screened a diverse library of 12 000 small molecular weight compounds randomly by in vitro strand-transfer assay. We identified a series of substituted carbazoles that exhibit strand-transfer inhibitory activity at low micromolar concentrations. Of these, the most potent compound exhibited an IC50 of 5.00+/-3.31 microM (CA-0). To analyse the structural determinants of strand-transfer inhibitory activity of the carbazole derivatives, we selected 23 such derivatives from our compound library and performed further analyses. Of these 23 compounds, six showed strong strand-transfer inhibition. The inhibition kinetics analyses and ethidium bromide displacement assays indicated that the carbazole derivatives are competitive inhibitors and not intercalators. An HeLa4.5/LTR-nEGFP cell line was employed to evaluate in vitro virus replication inhibition of the carbazole derivatives, and IC50 levels ranged from 0.48-1.52 microM. Thus, it is possible that carbazole derivatives, which possess structures different from previously-reported IN inhibitors, may become novel lead compounds in the development of IN inhibitors.


In situ X-ray diffraction study of the hydrothermal crystallization of hierarchical Bi₂WO₆ nanostructures.
The hydrothermal crystallization of hierarchical Bi₂WO₆ nanostructures has been monitored with in situ energy-dispersive X-ray diffraction (EDXRD). The kinetic data analysis according to the Avrami-Erofe'ev model suggests that the formation of nanostructured Bi₂(2)WO₆ is diffusion controlled with Avrami exponents around 0.5 and that the growth mechanism is temperature independent in the interval from 150 to 180°C. Furthermore, the reaction kinetics and the crystal structure of the resulting hydrothermal products depend on the pH value of the Bi(NO₃)₃·5H₂O/K₂WO₄ hydrothermal system.


Primary and repeat caesarean sections: comparison of indications.
In this retrospective study, we describe and compare the clinical indications of primary and repeat caesarean sections. We review caesarean deliveries at the Princess Badeea Teaching Hospital in North Jordan performed between 1 January and 26 November 1995 (n=740). The indication for the procedure was extracted based on the surgeon's operative reports. The hospital caesarean rate during the study period was 8.8%; 22.7% of these were repeat procedures (n=168). Elective caesarean delivery was the leading cause of repeat sections, followed by dystocia, others, breech and fetal distress. In contrast, breech presentation, dystocia and fetal distress were the leading indications for primary caesarean section. Ninetynine patients (59%) undergoing repeat caesarean had absolute or relative contraindication to trial of labour. The majority of primary caesarean are clinically indicated. Caesarean section rates can be lowered if we address the repeat elective procedures.


Cross-cultural adaptation and validation of the Quebec Back Pain Disability Scale to European Portuguese language.
Cross-cultural adaptation and psychometric testing. To conduct the cross-cultural adaptation of the Quebec Back Pain Disability Scale (QBPDS) and investigate its reliability and validity in patients with chronic low back pain (CLBP). The QBPDS is one of the most commonly used scales to evaluate functional incapacity resulting from low back pain. Although measuring disability is an important outcome in physiotherapy care, there is no previous research relating to the cultural adaptation and psychometric testing of the QBPDS in the Portuguese-speaking population. The questionnaire was first translated and back-translated in accordance with the published guidelines. The Portuguese version of the QBPDS was then pilot tested in a Portuguese sample of 40 patients with CLBP. Psychometric properties were evaluated in a new sample of 132 patients with CLBP. Exploratory factor analysis was performed to confirm its unidimensionality. Reliability was evaluated through internal consistency and reproducibility, using the Cronbach α and intraclass correlation coefficient, respectively. Construct validity was assessed with correlations between the QBPDS and the Roland-Morris Disability Questionnaire and between the QBPDS and the visual analogue pain scale for convergent validity and pain localization for discriminative validity, using the Spearman correlation analysis and the Mann-Whitney test. Exploratory factor analysis revealed the existence of one major factor that explains 52.1% of the variance. One-week test-retest reliability was 0.7, and internal consistency was 0.95. The QBPDS correlated strongly with the Roland-Morris Disability Questionnaire (0.62; P < 0.001), moderately with pain (0.38; P < 0.001), and shows capability to discriminate between patients with localized and referred pain (U = 1218; P < 0.0005). The reliability and construct validity of the Portuguese version of the QBPDS are acceptable to assess functional status of Portuguese-speaking patients with CLBP. .


Endocrine disruption by di-(2-ethylhexyl)-phthalate in Chinese rare minnow (Gobiocypris rarus).
Great concern has been raised over the potential impact of environmental contaminants on fish populations that inhabit the Three Gorge Reservoir. The present study investigated the endocrine-disrupting effects of di-(2-ethylhexyl)-phthalate (DEHP) on the Chinese rare minnow (Gobiocypris rarus), an endemic fish distributed in upstream waters in the Yangtze River. Adult rare minnow were exposed to environmentally relevant concentrations of DEHP (0 µg/L, 3.6 µg/L, 12.8 µg/L, 39.4 µg/L, and 117.6 µg/L) for a 21-d period. Then, concentrations of sex hormones in the plasma and relative transcription of various associated genes were measured in the hypothalamic-pituitary-gonadal (HPG) axis and liver of the fish. Exposure to DEHP resulted in greater circulating concentrations of testosterone (T) and lower concentrations of estradiol (E2), which were accompanied by upregulation of Cyp17 mRNA and downregulation of Cyp19a mRNA in the gonads of females. In males, increases of T and E2 levels were consistent with upregulation of Cyp17 and Cyp19a in the gonads. Furthermore, the T/E2 ratio was increased in females but reduced in males. A significant increase in the levels of hepatic vitellogenin (VTG) gene transcription was observed in both females and males. The present study showed that waterborne exposure to DEHP altered plasma sex hormone levels and modulated gene transcription profiles of associated genes in the HPG axis and liver, occurring mostly at higher concentrations (>39.4 µg/L), which suggests that environmental concentration of DEHP (5.4 µg/L) alone might not disturb the endocrine system of the rare minnow in the TGR.


Rational Design of Tungsten Selenide @ N-Doped Carbon Nanotube for High-Stable Potassium-Ion Batteries.
Potassium-ion batteries (PIBs) are deemed as one of the most promising energy storage systems due to their high energy density and low cost. However, their commercial application is far away from satisfactory because of limited suitable electrode materials. Herein, core-shell structured WSe2 @N-doped C nanotubes are rationally designed and synthesized via selenizing WO3 @ polypyrrole for the first time. The large interlayer spacing of WSe2 can facilitate the intercalation/deintercalation of K+ . Meanwhile, the core-shell structured nanotube provides favorable interior void space to accommodate the volume expansion of WSe2 during cycling. Thus, the obtained electrode exhibits superb electrochemical performance with a high capacity of 301.7 mAh g-1 at 100 mA g-1 over 120 cycles, and 122.1 mAh g-1 can remain at 500 mA g-1 even after 1300 cycles. Ex-situ X-ray diffraction analysis reveals the K-ion storage mechanism of WSe2 @N-doped C includes intercalation and conversion reaction. Density function theory (DFT) calculation demonstrates the reasonable diffusion pathway of K+ . In addition, the obtained WSe2 @N-doped C nanotubes have been used as anode material for lithium-ion batteries, which also show good rate performance and high cycle stability. Therefore, this work offers a new methodology for the ration design of new structure electrode materials with long cycle stability.


The morphogenetic regulator Czf1p is a DNA-binding protein that regulates white opaque switching in Candida albicans.
Czf1p has been demonstrated to regulate the switch between the yeast-cell morphology and filamentous morphologies of the human fungal pathogen Candida albicans. The predicted amino acid sequence of Czf1p contains a zinc-cluster motif similar to the DNA-binding domains of proteins such as Saccharomyces cerevisiae Gal4p, suggesting that Czf1p is a DNA-binding protein. Czf1p also demonstrates genetic interaction and a two-hybrid interaction with a second regulator of C. albicans cellular morphology, Efg1p. During growth in contact with an agar matrix, Efg1p has a negative effect on filamentation and Czf1p antagonizes this effect. In addition to regulating cellular morphology, Efg1p plays a role in regulating the cell-type switch between the commonly observed white phase of C. albicans and the opaque, mating-competent phase. While overexpression of EFG1 stimulates the switch from opaque to white, the results reported here demonstrate that overexpression of CZF1 promotes the reverse switch, from white to opaque. We also demonstrate that Czf1p binds CZF1 promoter DNA in vitro. Therefore, for the regulation of both contact-dependent filamentation and white-opaque switching, Czf1p and Efg1p have opposing functions.


Academic motivation and self-directed learning readiness of nursing students during the COVID-19 pandemic in three countries: A cross-sectional study.
It is crucial to evaluate student academic motivation and self-directed learning (SDL) readiness while teaching online or flexibly. During the coronavirus disease 2019 pandemic, there were few investigations on the link between academic motivation and SDL readiness. This study investigated the connection between academic motivation and SDL readiness and the three academic motivation domains' predictive features. This cross-sectional study used convenience sampling to recruit 1187 nursing students from four nursing colleges in three countries. We utilized the Academic Motivation Scale College Version and Self-directed Learning Readiness Scale for Nurse Education to collect data. Descriptive and inferential statistics were employed to analyze the data. Extrinsic motivation received the highest mean. Most nursing students exhibited SDL readiness, whereas "desire for learning" was rated the highest dimension of SDL readiness. We found significant differences in nursing students' intrinsic and extrinsic motivation and amotivation between the three countries. Finally, country, gender, and intrinsic motivation were significant predictors of the nursing students' SDL readiness. Among Filipino, Saudi, and Thai nursing students, their SDL readiness is influenced by the intrinsic motivation domain. Therefore, nursing students with higher levels of intrinsic motivation are proactive learners for SDL.


Human maxillary sinuses augmented with mineralized, solvent-dehydrated bone allograft: a longitudinal case series.
This prospective case series aimed to assess the clinical stability of maxillary sinus floors regenerated with mineralized, solvent-dehydrated bone allograft (MSDBA) and restored with dental implants after at least 5 years of function. Eleven sinuses in 7 patients (4 bilateral) were augmented with 50% cortical and 50% cancellous MSDBA (Puros, Zimmer Dental Italy srl, Vittorio Veneto, Treviso, Italy). After a mean healing period of 8.1 months, a total of 11 bone specimens (1 per sinus graft) were retrieved and 25 implants were placed. Bone samples were analyzed using histology, histomorphometry, and immunohistochemistry. Standardized periapical radiographs were taken at prosthetic loading (baseline) and annually. There were no complications or failures. Histologically, almost all residual MSDBA particles were surrounded by bone. Histomorphometry characterized the tissue as 39% ± 1.6% newly formed bone, 34% ± 1.6% marrow spaces, and 31% ± 1.4% residual material reflective of high cortical content of the composite graft. Immunohistochemistry indicated that osteoblasts expressed OB-cadherin at high levels. After a mean follow-up of 5.1 years, implants and regenerated bone appeared clinically stable. Radiographically, implants appeared to be surrounded by dense bone and ridges did not lose clinically measurable volume. Composite MSDBA allografts formed good quality maxillary sinus bone without complications after 8.1 months of mean healing time, and demonstrated clinical and radiographic stability after a mean follow-up time of 5.14 years.


A scanning electron microscopic study of the early response of lung tissue to amosite asbestos exposure.
The early response of the lung to a single exposure of amosite asbestos was examined via scanning electron microscopy and correlated light microscopy in the guinea pig model. At 2 h post-exposure, lesions consisted of discrete areas of atelectasis with influx of neutrophils and macrophages. Free asbestos fibres were evident in affected areas. By 4 h post exposure, affected regions were more extensive with phagocytic cell numbers increased both in reactive sites and in adjacent tissue. By 1 day post-exposure, the inflammatory response was well developed and encompassed wide areas of the lung. Activated phagocytes were congregated in atelectatic regions and on blood vessel walls. Numerous macrophages were present even in alveoli distant to reactive loci. The 6 day and 12 day time frames marked a subsiding of the inflammatory response in which macrophages outnumbered PMNs in the comparably fewer reactive areas. There was a notable decrease both in marginated leucocytes and in accumulations of phagocytes in tissue adjacent to affected regions.


Cluster of zoonotic cutaneous leishmaniasis (Leishmania major) in European travelers returning from Turkmenistan.
We report a cluster of cutaneous leishmaniasis due to Leishmania major in four immunocompetent travelers returning from Western Turkmenistan and having atypical and/or multiple lesions. Treatments with pentamidine or fluconazole were effective. Physicians should be aware that some virulent strains of L major currently circulate in Central Asia.


Single-cell heterogeneity and cell-cycle-related viral gene bursts in the human leukaemia virus HTLV-1.
Background: The human leukaemia virus HTLV-1 expresses essential accessory genes that manipulate the expression, splicing and transport of viral mRNAs. Two of these genes, tax and hbz, also promote proliferation of the infected cell, and both genes are thought to contribute to oncogenesis in adult T-cell leukaemia/lymphoma. The regulation of HTLV-1 proviral latency is not understood. tax, on the proviral plus strand, is usually silent in freshly-isolated cells, whereas the minus-strand-encoded hbz gene is persistently expressed at a low level. However, the persistently activated host immune response to Tax indicates frequent expression of tax in vivo. Methods: We used single-molecule RNA-FISH to quantify the expression of HTLV-1 transcripts at the single-cell level in a total of >19,000 cells from five T-cell clones, naturally infected with HTLV-1, isolated by limiting dilution from peripheral blood of HTLV-1-infected subjects. Results: We found strong heterogeneity both within and between clones in the expression of the proviral plus-strand (detected by hybridization to the tax gene) and the minus-strand ( hbz gene). Both genes are transcribed in bursts; tax expression is enhanced in the absence of hbz, while hbz expression increased in cells with high tax expression. Surprisingly, we found that hbz expression is strongly associated with the S and G 2/M phases of the cell cycle, independent of tax expression. Contrary to current belief, hbz is not expressed in all cells at all times, even within one clone. In hbz-positive cells, the abundance of hbz transcripts showed a very strong positive linear correlation with nuclear volume. Conclusions: The occurrence of intense, intermittent plus-strand gene bursts in independent primary HTLV-1-infected T-cell clones from unrelated individuals strongly suggests that the HTLV-1 plus-strand is expressed in bursts in vivo. Our results offer an explanation for the paradoxical correlations observed between the host immune response and HTLV-1 transcription.


Crystal structures of Au2 complex and Au25 nanocluster and mechanistic insight into the conversion of polydisperse nanoparticles into monodisperse Au25 nanoclusters.
We previously reported a size-focusing conversion of polydisperse gold nanoparticles capped by phosphine into monodisperse [Au(25)(PPh(3))(10)(SC(2)H(4)Ph)(5)Cl(2)](2+) nanoclusters in the presence of phenylethylthiol. Herein, we have determined the crystal structure of [Au(25)(PPh(3))(10)(SC(2)H(4)Ph)(5)Cl(2)](2+) nanoclusters and also identified an important side-product-a Au(I) complex formed in the size focusing process. The [Au(25)(PPh(3))(10)(SC(2)H(4)Ph)(5)Cl(2)](2+) cluster features a vertex-sharing bi-icosahedral core, resembling a rod. The formula of the Au(I) complex is determined to be [Au(2)(PPh(3))(2)(SC(2)H(4)Ph)](+) by electrospray ionization (ESI) mass spectrometry, and its crystal structure (with SbF(6)(-) counterion) reveals Au-Au bridged by -SC(2)H(4)Ph and with terminal bonds to two PPh(3) ligands. Unlike previously reported [Au(2)(PR(3))(2)(SC(2)H(4)Ph)](+) complexes in the solid state, which exist as tetranuclear complexes (i.e., dimers of [Au(2)(PR(3))(2)(SC(2)H(4)Ph)](+) units) through a Au···Au aurophilic interaction, in our case we found that the [Au(2)(PPh(3))(2)(SC(2)H(4)Ph)](+) complex exists as a single entity, rather than being dimerized to form a tetranuclear complex. The observation of this Au(I) complex allows us to gain insight into the intriguing conversion process from polydisperse Au nanoparticles to monodisperse Au(25) nanoclusters.


Antibacterial effects of 4-META/MMA-TBB resin containing chlorhexidine.
This study evaluated the antibacterial effects of 4-acryloyloxyethyl trimellitate anhydride/methyl methacrylate-tri-n-butylborane (4-META/MMA-TBB) resin containing chlorhexidine (CHX) digluconate. The CHX was incorporated into the resins at varying concentrations from 0.0 (control) to 3.0%. The antibacterial effect of each resin against seven microorganisms was examined using agar diffusion tests. Growth inhibition of two streptococci was also tested in brain heart infusion (BHI) liquid broth containing each resin. Release of CHX was analyzed using HPLC, and enamel and dentin bond strengths of each resin were measured. In the agar diffusion tests, growth of all the microorganisms was inhibited by the resin specimens containing CHX at 1.0% or higher except for Enterococcus faecalis. There was greater sensitivity in Streptococcus mutans and Streptococcus sobrinus than in the other bacteria tested. Complete growth inhibition of these two streptococci was observed in BHI liquid broth containing 1.0-1.5% or greater CHX-incorporated resin. According to HPLC analysis, 1.0% and 1.5% CHX-containing resins released means of 3.63 and 8.59 microg/mL of CHX, respectively. Specimens with 0.5-1.5% and 0.5-2.0% CHX exhibited no significant reduction in enamel and dentin bond strengths, respectively, when compared to the control (p > 0.05). This in vitro study suggested that incorporation of 1.0-1.5% CHX digluconate into the 4-META resin is optimal in terms of antibacterial effects and bond strength to the tooth.


[Identification of enterotoxin-producing Clostridium perfringens by the polymerase chain reaction].
Polymerase chain reaction was applied to identify enterotoxin-producing Clostridium perfringens by amplifying a segment of the C. perfringens enterotoxin gene. All of the four enterotoxin-positive reference strains tested were PCR positive while an enterotoxin-negative strain was PCR positive. All 17 clostridial strains (16 species) other than C. perfringens were PCR negative. With clinical strains isolated from various clinical specimens in Japan, Korea, and Thailand, all three enterotoxin-positive isolates were PCR positive and all 82 enterotoxin-negative isolates were PCR negative. PCR results for amplifying a region containing the initiation codon of the C. perfringens enterotoxin gene also demonstrated complete agreement with enterotoxin producibility. These results suggested that the PCR assay is a rapid and simple test for identifying the enterotoxin-producing C. perfringens without using any cultures and spore treatments.


Erythropoietin profile in spinal cord injured patients.
Patients with spinal cord injury (SCI) have a high incidence of anemia. Intact erythropoietin (EPO) production is essential to the maintenance of erythrocyte mass and prevention and correction of anemia. However, the effect of chronic SCI on EPO production remains unclear. We measured plasma EPO concentration in 83 men with longstanding SCI and a group of normal able-bodied individuals. The SCI patients showed a significant reduction in hematocrit, a high prevalence of anemia, and an increased plasma EPO concentration. Active smokers showed a significantly higher hematocrit and lower EPO concentration than nonsmokers. No significant difference was found in hematocrit or EPO between individuals with paraplegia and those with quadriplegia. A negative correlation was found between EPO and hematocrit in SCI patients lacking significant lung disease. Thus, in the absence of renal insufficiency, EPO response to anemia is qualitatively preserved in SCI patients and is largely independent of the level of injury.


Plants under Climatic Stress: V. Chilling and Light Effects on Radiocarbon Exchange between Photosynthetic Intermediates of Sorghum.
Patterns of radiocarbon exchange between photosynthetic intermediates of the chilling sensitive Sorghum bicolor were modified by exposure to a combined environmental stress of low temperature (10 C) and moderate light levels (170 w.m(-2), visible). Pulse chase experiments with(14)CO(2) showed that this stress initially slowed the release of photosynthetically absorbed radiocarbon from malate. Further exposure caused an increased proportion of the radiocarbon to accumulate in aspartate. This trend continued, so that after 30 hours, some 80% of absorbed radiocarbon remained in aspartate after 1 minute of chasing and subsequent release of carbon into the C(3) cycle was very slow. In Sorghum, chilling combined with light seemed to cause a restriction in an early step of the C(4) pathway before ultrastructural changes could be detected in the mesophyll chloroplasts.


Binding of λ-carrageenan (a food additive) to almond cystatin: An insight involving spectroscopic and thermodynamic approach.
Carrageenan is a high molecular weight linear sulphated polysaccharide, primarily used in food industry as gelling, thickening, and stabilizing agent. Almond milk prepared from almonds is low in fat, but high in antioxidants, energy, proteins, lipids and fibre. Purified almond cystatin was incubated with increasing concentrations of carrageenan at 25°C for different time interval and significant loss in inhibitory activity was observed. Interaction between carrageenan and cystatin resulted in complex formation as depicted by the decrease in fluorescence intensity with increase in the concentration of carrageenan. Stern-volmer analysis of fluorescence quenching data showed binding constant to be 1.84±0.20×104M-1 and number of binding sites close to unity. These results were further confirmed by supporting results obtained in UV-vis spectroscopy. FTIR analysis shows significant shift in the peak intensity and this change clearly depict change in the structure of cystatin from that of α helix to β-sheet. CD spectra further confirmed the structural transition of the cystatin from α helix to β-sheet structure on interaction with increased concentrations of carrageenan. The contributing thermodynamic parameters were determined by ITC. The negative ΔH° and positive TΔS° values suggest involvement of electrostatic forces and hydrophobic interaction in the formation of the λ-carrageenan-cystatin complex.


Construction of Bi2MoO6/CdS heterostructures with enhanced visible light photocatalytic activity for fuel denitrification.
In this work, a novel step-scheme (S-scheme) Bi2MoO6/CdS heterojunction (HJ) photocatalyst (PC) was successfully prepared by a two-step solvothermal method for the first time. One-dimensional CdS nanorods were prepared by a simple solvothermal method as a synthesis template. Then, a Bi2MoO6 precursor was added to obtain a series of Bi2MoO6/CdS HJ composite catalytic materials with different morphologies. The photocatalytic performance of the catalyst was investigated by simulating fuel denitration as a probe reaction under visible light excitation (>420 nm). When compared with pure Bi2MoO6 and CdS, the 0.65-Bi2MoO6/CdS composite shows the highest photocatalytic activity for pyridine degradation. Degradation of pyridine reached 81% after 240 min of visible light excitation. The degradation rate of 0.65-Bi2MoO6/CdS reached 0.4471 h-1, which was 1.8 and 3.2 times higher than that of CdS (0.2493 h-1) and Bi2MoO6 (0.1427 h-1), respectively. Combined with a series of characterisation results, the improvement in pyridine degradation activity was mainly attributed to (1) the S-scheme HJ structure between Bi2MoO6 and CdS, which greatly promoted the separation of photogenerated electrons and holes while retaining its strong redox ability, (2) the large specific surface area, which provided abundant active sites and efficient adsorption performance and catalytic performance, and (3) the special morphology, which induced multiple reflections of light, thereby improving absorption and utilisation of light. Moreover, after four cycles of pyridine denitrification, the samples still exhibited high activity, indicating good stability and recyclability of the composite catalyst. These findings provide a basis for the development of composite PCs for efficient fuel denitration under visible light irradiation.


The imaging features of post-traumatic myositis ossificans, with emphasis on MRI.
Post-traumatic myositis ossificans is a benign condition of heterotopic bone formation, which can mimic soft-tissue and bone malignancies. This pictorial review describes the specific imaging features of myositis ossificans using different imaging techniques, but with emphasis on MRI.


A new approach for freezing of aqueous solutions under active control of the nucleation temperature.
An experimental setup for controlled freezing of aqueous solutions is introduced. The special feature is a mechanism to actively control the nucleation temperature via electrofreezing: an ice nucleus generated at a platinum electrode by the application of an electric high voltage pulse initiates the crystallization of the sample. Using electrofreezing, the nucleation temperature in pure water can be precisely adjusted to a desired value over the whole temperature range between a maximum temperature Tn(max) close to the melting point and the temperature of spontaneous nucleation. However, the presence of additives can inhibit the nucleus formation. The influence of hydroxyethylstarch (HES), glucose, glycerol, additives commonly used in cryobiology, and NaCl on Tn(max) were investigated. While the decrease showed to be moderate for the non-ionic additives, the hindrance of nucleation by ionic NaCl makes the direct application of electrofreezing in solutions with physiological salt concentrations impossible. Therefore, in the multi-sample freezing device presented in this paper, the ice nucleus is produced in a separate volume of pure water inside an electrode cap. This way, the nucleus formation becomes independent of the sample composition. Using electrofreezing rather than conventional seeding methods allows automated freezing of many samples under equal conditions. Experiments performed with model solutions show the reliability and repeatability of this method to start crystallization in the test samples at different specified temperatures. The setup was designed to freeze samples of small volume for basic investigations in the field of cryopreservation and freeze-drying, but the mode of operation might be interesting for many other applications where a controlled nucleation of aqueous solutions is of importance.


Assessment of worker exposure to airborne molds in honeybee overwintering facilities.
Airborne fungi in honeybee overwintering and equipment cleaning facilities were enumerated and identified to determine worker exposure during cleaning and routine beekeeping operations. Testing was prompted by observations of extensive mold growth on dead bees and associated material and by results of a preliminary study at one Alberta beekeeping facility that showed very high numbers of mold colonies on air samples taken during worker activity. To evaluate whether high mold counts were indicative of a problem at a single site or were industry wide, approximately 120 air samples were collected with a Reuter centrifugal sampler inside 10 overwintering facilities before and during routine beekeeping activity during fall, winter, and spring periods. A set of 30 samples was collected from 15 sites used for annual equipment cleaning. This study showed that average spore counts per overwintering site ranged from 238 to 1442 colony-forming units (CFU)/m3 prior to disturbance by workers and from 2200 to 13,931 CFU/m3 while workers swept up dead bees. Levels of airborne molds recovered during annual cleaning of beekeeping equipment ranged from 300 to 54,700 CFU/m3 with an average of 16,083 CFU/m3. Potentially toxigenic, pathogenic, or allergenic molds were recovered at all sites. Since the data indicate that exposure to high levels of airborne molds is widespread throughout the industry, actions that might help minimize worker exposure are discussed.


The potential use of microRNAs as a therapeutic strategy for SARS-CoV-2 infection.
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, there is no effective therapeutic approach for treating SARS-CoV-2 infections. MicroRNAs (miRNAs) have been recognized to target the viral genome directly or indirectly, thereby inhibiting viral replication. Several studies have demonstrated that host miRNAs target different sites in SARS-CoV-2 RNA and constrain the production of essential viral proteins. Furthermore, miRNAs have lower toxicity, are more immunogenic, and are more diverse than protein-based and even plasmid-DNA-based therapeutic agents. In this review, we emphasize the role of miRNAs in viral infection and their potential use as therapeutic agents against COVID-19 disease. The potential of novel miRNA delivery strategies, especially EDV™ nanocells, for targeting lung tissue for treatment of SARS-CoV-2 infection is also discussed.


The C. elegans Excretory Canal as a Model for Intracellular Lumen Morphogenesis and In Vivo Polarized Membrane Biogenesis in a Single Cell: labeling by GFP-fusions, RNAi Interaction Screen and Imaging.
The four C. elegans excretory canals are narrow tubes extended through the length of the animal from a single cell, with almost equally far extended intracellular endotubes that build and stabilize the lumen with a membrane and submembraneous cytoskeleton of apical character. The excretory cell expands its length approximately 2,000 times to generate these canals, making this model unique for the in vivo assessment of de novo polarized membrane biogenesis, intracellular lumen morphogenesis and unicellular tubulogenesis. The protocol presented here shows how to combine standard labeling, gain- and loss-of-function genetic or RNA interference (RNAi)-, and microscopic approaches to use this model to visually dissect and functionally analyze these processes on a molecular level. As an example of a labeling approach, the protocol outlines the generation of transgenic animals with fluorescent fusion proteins for live analysis of tubulogenesis. As an example of a genetic approach, it highlights key points of a visual RNAi-based interaction screen designed to modify a gain-of-function cystic canal phenotype. The specific methods described are how to: label and visualize the canals by expressing fluorescent proteins; construct a targeted RNAi library and strategize RNAi screening for the molecular analysis of canal morphogenesis; visually assess modifications of canal phenotypes; score them by dissecting fluorescence microscopy; characterize subcellular canal components at higher resolution by confocal microscopy; and quantify visual parameters. The approach is useful for the investigator who is interested in taking advantage of the C. elegans excretory canal for identifying and characterizing genes involved in the phylogenetically conserved processes of intracellular lumen and unicellular tube morphogenesis.


Anisotropy induced localization of pseudo-relativistic spin states in graphene double quantum wire structures.
We study the single-particle properties of Dirac Fermions confined to a double quantum wire system based on graphene. We map out the spatial regions where electrons in a given subband display the largest occupation probability induced by spatial anisotropic effects associated to the interaction strength between the graphene wires and the substrate. Here, the graphene-substrate interaction is considered as an ad hoc parameter which destroys the zero-gap observed in the relativistic Dirac cone characteristic of graphene electronic energy dispersions. Furthermore, the results indicate that the character of quasi-extended spin states, viewed by multisubband probability density function, is highly sensitive to spatial asymmetries and to the graphene-substrate interaction strength.


Biotransformation of butachlor through mercapturic acid pathway in rat tissue homogenates.
The metabolism of butachlor was studied in rat liver and kidney homogenates. In vitro incubation of butachlor with liver fractions (S9, microsome, and cytosolic fractions) formed a considerable amount of butachlor glutathione conjugate (BGSC), while the conjugating activity was not efficient for the kidney S9 fraction. There is a sex difference in the distribution of glutathione S-transferase in the liver. It seems that more enzyme activity is detected in the female liver microsome, while this is not the case in its cytosolic fraction. Further biotransformation of BGSC to mercapturate was not observed in the liver S9 fraction. This metabolite was further transformed to butachlor acetyl cysteine conjugate (BACC) in the presence of acetyl CoA, but to butachlor cysteine conjugate (BCC) in the absence of acetyl CoA. These findings demonstrated that butachlor is initially conjugated with GSH to form BGSC by the enzyme glutathione S-transferase in the liver. This metabolite is apparently transported to the kidneys, where it is transformed to the mercapturate.


Multiple muscle tear after fall on buttock-role of conservative management and exercise for early recovery and return to play.
to describe role of alternative management as an approach to management and rehabilitation of multiple hip muscles tears by the use of 1 RM (Repetition Maximum) testing and hip muscle strengthening program along with the use of sports specific drills for rehabilitation and recovery. There is very limited literature describing multiple hip muscle tears and the conservative management of the same. 1RM testing and strengthening of hip muscles is an approach that is able to help in the return to sports of an athlete without surgical intervention. the patient, is a 21-year-old male hockey player who presented with pain right buttock, right lower leg and a limp on the right side while walking. Physical examination revealed a positive Trendelenburg sign both in stance and gait phase. Hip rotational movements showed a normal range of motion, there was a severe pain in the right buttock on movements which he described at 8/10 on VAS (Visual Analogue Scale). Strength assessment revealed weakness of the right hip flexors and extensors and also of the abductor and external hip rotator muscles. Treatment protocol followed was based on 1 RM testing of muscles and hip strengthening exercises and sports specific drills. following the intervention, the patient reported pain at 0/10 VAS while doing all activities and also showed good muscle control with no limp. this highlights an alternative protocol for treating multiple hip muscle tears and illustrates the importance of 1 RM testing as a part of examination and sports medicine intervention.


ALCAM regulates mediolateral retinotopic mapping in the superior colliculus.
ALCAM [activated leukocyte cell adhesion molecule (BEN/SC-1/DM-GRASP)] is a transmembrane recognition molecule of the Ig superfamily (IgSF) containing five Ig domains (two V-type, three C2-type). Although broadly expressed in the nervous and immune systems, few of its developmental functions have been elucidated. Because ALCAM has been suggested to interact with the IgSF adhesion molecule L1, a determinant of retinocollicular mapping, we hypothesized that ALCAM might direct topographic targeting to the superior colliculus (SC) by serving as a substrate within the SC for L1 on incoming retinal ganglion cell (RGC) axons. ALCAM was expressed in the SC during RGC axon targeting and on RGC axons as they formed the optic nerve; however, it was downregulated distally on RGC axons as they entered the SC. Axon tracing with DiI revealed pronounced mistargeting of RGC axons from the temporal retina half of ALCAM null mice to abnormally lateral sites in the contralateral SC, in which these axons formed multiple ectopic termination zones. ALCAM null mutant axons were specifically compromised in medial orientation of interstitial branches, which is known to require the ankyrin binding function of L1. As a substrate, ALCAM-Fc protein promoted L1-dependent attachment of acutely dissociated retinal cells and an L1-expressing, ALCAM-negative cell line, consistent with an ALCAM-L1 heterophilic molecular interaction. Together, these results suggest a model in which ALCAM in the SC interacts with L1 on RGC axons to promote medial extension of RGC axon branches important for mediolateral axon targeting in the formation of retinocollicular maps.


A molecular understanding of alphavirus entry.
Alphaviruses cause severe human illnesses including persistent arthritis and fatal encephalitis. As alphavirus entry into target cells is the first step in infection, intensive research efforts have focused on elucidating aspects of this pathway, including attachment, internalization, and fusion. Herein, we review recent developments in the molecular understanding of alphavirus entry both in vitro and in vivo and how these advances might enable the design of therapeutics targeting this critical step in the alphavirus life cycle.


Fractures and dislocations of the cervicothoracic junction.
Presented is a retrospective review of case notes and all available imaging studies in seven patients with acute fractures-dislocations of the cervicothoracic junction. Imaging studies included radiographs (five cases), computed tomography (six cases), and magnetic resonance imaging (seven cases). The study group consisted of five men and two women with mean age at presentation of 43.6 years (range 25-69 years). Four patients had been in road traffic accidents, whereas three patients had had falls. Three patients sustained complete neurologic deficits with no recovery, whereas the remaining four had no abnormal neurology or mild deficit at presentation and were normal at final follow-up. The injury was missed initially in three cases. The commonest injury pattern was traumatic spondylolisthesis of C7 on T1 with multilevel neural arch fractures, resulting in increased anteroposterior canal dimensions (four cases). Bilateral pars fractures of C7 and pure facet dislocation were seen in one case each. Neurologic deficit was related to the degree of anterior displacement of C7 on T1. Fracture-dislocation at the cervicothoracic junction is a rare injury with a variation of injury patterns and neurologic outcome.


Negative interference from immunoglobulin M paraproteinaemia on the Roche enzymatic creatinine method.
Although enzymatic creatinine methods are subject to fewer interferences than traditional Jaffe creatinine methods, every method in clinical chemistry has limitations. We report, for the first time in the literature, a case of an immunoglobulin M (IgM) paraproteinaemia causing an undetectably low creatinine result on the Roche enzymatic assay. This interference did not occur with other enzymatic creatinine methods produced by Abbott and Siemens or the Roche Jaffe, VITROS dry slide and liquid chromatography with tandem mass spectrometry (LC-MS/MS) creatinine methods. IgM interference was confirmed as patient serum precipitated with polyethylene glycol (PEG) and anti-IgM antiserum yielded detectable Roche enzymatic creatinine results comparable to unaffected methods. The patient's serum formed an obvious precipitate when mixed with reagent one of the Roche enzymatic creatinine method. This is in contrast to a report of positive interference from IgM paraproteinaemia in a different enzymatic creatinine method, which showed that a precipitate formed when mixing blood with reagent two. As each patient's paraprotein has a unique structure, it is possible that there are variations in the chemical characteristics of IgM paraproteins between patients. This, as well as IgM-class antibodies' tendency to form multimers and aggregates, can lead to unpredictable assay interferences and precipitation tendencies between different manufacturers of enzymatic creatinine reagents and their incubation steps. This case highlights the importance of continuing to question and investigates results that do not fit the clinical picture, especially as more laboratories switch from primarily using traditional Jaffe creatinine methods to enzymatic creatinine methods.


Multi-responsive on-demand drug delivery PMMA-co-PDEAEMA platform based on CO2, electric potential, and pH switchable nanofibrous membranes.
This study investigated the release characteristics of curcumin (CUR)-loaded switchable poly(methyl methacrylate)-co-poly(N,N-diethylaminoethyl methacrylate) (PMMA-co-PDEAEMA) membranes following the application of various stimuli, as well as the platform's applicability in wound dressing and tissue engineering applications. The free-radical polymerization method was used to synthesize the PMMA-co-PDEAEMA copolymer. The drug-loaded nanofibrous membrane with electric potential (EP)-, CO2-, and pH-responsive properties was developed by the electrospinning of PMMA-co-PDEAEMA and CUR. The resulted structure was characterized by a scanning electron microscope (SEM) coupled with X-ray energy dispersive spectroscopy and wide-angle X-ray scattering measurements. The release characteristics of the CUR-loaded wound covering were analyzed in various simulated environments at varying voltages, alternated CO2/N2 gas bubbling, and at two different pH values; the results demonstrated high drug release controllability. Loaded CUR displayed high stability and better solubility compared with free CUR. The CUR-loaded tissue also exhibited high antibacterial activity against Escherichia coli and staphylococcus aureus bacteria. In addition, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay depicted high biocompatibility of up to 95% in the CUR-loaded membrane. This platform could be a promising candidate for usage in tissue engineering and medical applications such as targeted drug delivery, biodetection, reversible cell capture-and-release systems, and biosensors.


ER-golgi traffic is a prerequisite for efficient ER degradation.
Protein quality control is an essential function of the endoplasmic reticulum. Misfolded proteins unable to acquire their native conformation are retained in the endoplasmic reticulum, retro-translocated back into the cytosol, and degraded via the ubiquitin-proteasome system. We show that efficient degradation of soluble malfolded proteins in yeast requires a fully competent early secretory pathway. Mutations in proteins essential for ER-Golgi protein traffic severely inhibit ER degradation of the model substrate CPY*. We found ER localization of CPY* in WT cells, but no other specific organelle for ER degradation could be identified by electron microscopy studies. Because CPY* is degraded in COPI coat mutants, only a minor fraction of CPY* or of a proteinaceous factor required for degradation seems to enter the recycling pathway between ER and Golgi. Therefore, we propose that the disorganized structure of the ER and/or the mislocalization of Kar2p, observed in early secretory mutants, is responsible for the reduction in CPY* degradation. Further, we observed that mutations in proteins directly involved in degradation of malfolded proteins (Der1p, Der3/Hrd1p, and Hrd3p) lead to morphological changes of the endoplasmic reticulum and the Golgi, escape of CPY* into the secretory pathway and a slower maturation rate of wild-type CPY.


A Personal History in Parasitic Weeds and Their Control.
This invited paper summarises a career in which I became increasingly involved in research and related activities on Striga and other parasitic weeds. It also presents a personal view of the present status of parasitic weed problems and their control.


Aging and regional differences in fat cell progenitors - a mini-review.
Fat mass and fat tissue distribution change dramatically throughout life. In old age, fat becomes dysfunctional and is redistributed from subcutaneous to intra-abdominal visceral depots as well as other ectopic sites, including bone marrow, muscle and the liver. These changes are associated with increased risk of metabolic syndrome. Fat tissue is a nutrient storage, endocrine and immune organ that undergoes renewal throughout the lifespan. Preadipocytes, which account for 15-50% of cells in fat tissue, give rise to new fat cells. With aging, declines in preadipocyte proliferation and differentiation likely contribute to increased systemic exposure to lipotoxic free fatty acids. Age-related fat tissue inflammation is related to changes that occur in preadipocytes and macrophages in a fat depot-dependent manner. Fat tissue inflammation frequently leads to further reduction in adipogenesis with aging, more lipotoxicity and activation of cellular stress pathways that, in turn, exacerbate inflammatory responses of preadipocytes and immune cells, establishing self-perpetuating cycles that lead to systemic dysfunction. In this review, we will consider how inherent, age-related, depot-dependent alterations in preadipocyte function contribute to age-related fat tissue redistribution and metabolic dysfunction.


TreeGeneBrowser: phylogenetic data mining of gene sequences from public databases.
Sequence databases represent an enormous resource of phylogenetic information, but there is a lack of tools for accessing that information in order to assess the amount of evolutionary information in these databases that may be suitable for phylogenetic reconstruction and for identifying areas of the taxonomy that are under-represented for specific gene sequences. We have developed TreeGeneBrowser which allows inspection and evaluation of gene sequence data for phylogenetic reconstruction. This program improves the efficiency of identification of genes that may be useful for particular phylogenetic studies and identifies taxa and taxonomic branches that are under-represented in sequence databases.


Finger on the Pulse: Pumping Iron into Chickpea.
Iron deficiency is a major problem in both developing and developed countries, and much of this can be attributed to insufficient dietary intake. Over the past decades several measures, such as supplementation and food fortification, have helped to alleviate this problem. However, their associated costs limit their accessibility and effectiveness, particularly amongst the financially constrained. A more affordable and sustainable option that can be implemented alongside existing measures is biofortification. To date, much work has been invested into staples like cereals and root crops-this has culminated in the successful generation of high iron-accumulating lines in rice and pearl millet. More recently, pulses have gained attention as targets for biofortification. Being secondary staples rich in protein, they are a nutritional complement to the traditional starchy staples. Despite the relative youth of this interest, considerable advances have already been made concerning the biofortification of pulses. Several studies have been conducted in bean, chickpea, lentil, and pea to assess existing germplasm for high iron-accumulating traits. However, little is known about the molecular workings behind these traits, particularly in a leguminous context, and biofortification via genetic modification (GM) remains to be attempted. This review examines the current state of the iron biofortification in pulses, particularly chickpea. The challenges concerning biofortification in pulses are also discussed. Specifically, the potential application of transgenic technology is explored, with focus on the genes that have been successfully used in biofortification efforts in rice.


Pathogenic mechanisms linking benign prostatic hyperplasia, lower urinary tract symptoms and erectile dysfunction.
Erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) are clinical entities very prevalent in men aged over 50 years. There is evidence that both may have a common pathophysiology. The objective of this study was to conduct a literature review aiming to show theories and hypotheses that justify a single pathophysiology for ED and LUTS/BPH. A search in Medline using the keywords of the Medical Subject Headings (MESH) 'erectile dysfunction' and 'lower urinary tract symptoms' in all fields of the database up to 15 December 2012. This search found 198 relevant articles that were analyzed. The data and articles were divided according to the type of evidence found. There are strong epidemiological data showing that LUTS/BPH is a risk factor for developing ED. Several experimental models demonstrated partial obstruction of the bladder in animals causes voiding disorders as well as a negative impact on erectile function of the operated animals. The increased adrenergic tonus in animals leads to prostate growth and urodynamic conditions similar to those found in men with LUTS and ED. Arteriosclerosis may lead to loss of vesical complacency, urinary tract obstruction and fibrosis of the cavernous bodies. The use of phosphodiesterase type 5 inhibitors (PDE-5i) and/or alpha-adrenergic blockers to treat ED and LUTS/BPH reinforces the hypothesis that, at least in some patients, both clinical pictures may have the same pathophysiology.


[Current research status on pelvic autonomic nerve monitoring in rectal cancer surgery].
Rectal cancer is a common malignant tumor of the digestive tract, and surgery is the main treatment strategy. Disorders of bowel, anorectal and urogenital function remain common problems after total mesorectal resection (TME), which seriously decreases the quality of life of patients. Surgical nerve damage is one of the main causes of the complications, while TME with pelvic autonomic nerve preservation is an effective way to reduce the occurrence of adverse outcomes. Intraoperative nerve monitoring (IONM) is a promising method to assist the surgeon to identify and protect the pelvic autonomic nerves. Nevertheless, the monitoring methods and technical standards vary, and the clinical use of IONM is still limited. This review aims to summarize the researches on IONM in rectal and pelvic surgery. The electrical nerve stimulation technique and different methods of IONM in rectal cancer surgery are introduced. Also, the authors discuss the limitations of current researches, including methodological disunity and lack of equipment, then prospect the future direction in this field.


Isotachophoresis preconcentration integrated microfluidic chip for highly sensitive genotyping of the hepatitis B virus.
The genotyping of hepatitis B virus (HBV) has become recently a valuable tool not only for epidemiological reasons but also for the clinical practice. Conventional methods for HBV genotyping typically include amplification of the target DNA sequences with a two-round nested PCR followed by separation of the amplified fragments by gel electrophoresis. A microfluidic chip that couples isotachophoresis (ITP) preconcentration and zone electrophoresis (ZE) separation may provide great advantages for sensitive, rapid and cost-effective clinical analysis. In this study, an HBV genotyping method with only one amplification round was developed by the application of the ITP-ZE chip. All the analysis steps of the ITP-ZE separation including sample injection, stacking and separation were performed continuously, controlled by sequential high-voltage switching. A 2.1cm sample plug was preconcentrated between discontinuous buffers in ITP process, followed by ZE separation. Sensitivity enhancement was obtained through the increase of sample loading volume. The average LOD value of the ITP-ZE microfluidic chip was determined to be 0.0021pg/muL. In a large-scale HBV genotyping test, single round PCR products were analyzed by ITP-ZE microfluidic chip, and the results were compared with that of the conventional method. Among the 200 cases studied, the classification rate obtained with microfluidic chip was 93%, which was 6% higher than that obtained with the conventional method. Method with ITP-ZE chip analysis provides HBV genotyping information in reduced PCR amplification time with higher detection rate when compared with conventional method. This method holds great potential for extrapolation to the abundance of similar molecular biology-based techniques in clinical diagnosis.


Mucinoprotein is a universal constituent of stable intercellular bridges in Drosophila melanogaster germ line and somatic cells.
Intercellular bridges formed by incomplete cytokinesis may be important in a variety of processes, including synchronization of mitotic and meiotic divisions in animal cells. Using specific antibodies against a mucin-type glycoprotein (Kramerov et al. [1996] FEBS Lett. 378:213-218) from Drosophila melanogaster cultured embryonic cells, we showed that this glycoprotein is located in all cytoplasmic bridges found in various germline and somatic tissues. In the ovary, immunostaining of ring canals connecting germ cells can be detected in the very early stages at the germarium region 1 where first gonial divisions take place, and the immunostaining appears to persist through late stages when transport of cytoplasm from nurse cells to a growing oocyte occurs. Each ring canal is made up of an outer and an inner rim. Mucin glycoprotein appears to be one of the first proteins localized to the outer rim, which is a derivative of the arrested cleavage furrow. The known ring canal proteins, phosphotyrosine-containing protein(s), F-actin, hts- and kelch proteins, are localized to the inner rim at a later developmental time. Similarly, mucin glycoprotein is recruited early to ring canals connecting mitotic primary spermatocytes in both larval and adult testes. Mucin glycoprotein was found to be present in intercellular bridges (small ring canals) in somatic cells, including follicular epithelium in ovary and imaginal disc cells. Intercellular bridges were observed for the first time in a subset of cells in the larval brain. Thus, mucin glycoprotein is the only protein hitherto found in all known types of stable intercellular bridges and may be an important constituent of a backbone needed for assembly and preservation of this particular type of cell-cell contact.


Linking the clinical vocabulary of diseases to the genes by mapping UMLS to OMIM allelic variant fields.
To link clinical vocabulary of diseases to gene entries in Online Mendelian Inheritance in Man (OMIM), we comprehensively matched diseases from Unified Medical Language System (UMLS) Metathesaurus to the OMIM text in Allelic Variant fields that describe relations between the mutations or polymorphisms of the genes and the phenotypes. Out of 1,786 genes having the field, 1,445 genes (80.9%) had matches with 2,417 types of diseases or disorders. The links are accessible at http://www.genelexpo.jp/diseases/.


IL-6 blockade therapy for inflammatory diseases: current perspectives and future directions.
Interleukin-6 (IL-6) is a prototypical cytokine featuring pleiotropic and redundant activity. It is an essential factor to protect host from environmental stress and to maintain homeostasis, whereas its dysregulated, excessive or persistent production plays a pathological role in various inflammatory diseases. Then, IL-6 blockade was expected to become a novel therapeutic strategy and a humanized anti-IL-6 receptor antibody, tocilizumab was developed. Indeed, through clinical trials its efficacy and tolerable safety was proved and is now in clinical use for the treatment of chronic inflammatory diseases such as rheumatoid arthritis, juvenile idiopathic arthritis and Castleman's disease. Moreover, ongoing various clinical studies suggest that it will be widely applicable for the treatment of intractable chronic immune-mediated diseases as well as acute severe inflammatory diseases presenting with "cytokine storm".


Impacts of Climate Change on Native Landcover: Seeking Future Climatic Refuges.
Climate change is a driver for diverse impacts on global biodiversity. We investigated its impacts on native landcover distribution in South America, seeking to predict its effect as a new force driving habitat loss and population isolation. Moreover, we mapped potential future climatic refuges, which are likely to be key areas for biodiversity conservation under climate change scenarios. Climatically similar native landcovers were aggregated using a decision tree, generating a reclassified landcover map, from which 25% of the map's coverage was randomly selected to fuel distribution models. We selected the best geographical distribution models among twelve techniques, validating the predicted distribution for current climate with the landcover map and used the best technique to predict the future distribution. All landcover categories showed changes in area and displacement of the latitudinal/longitudinal centroid. Closed vegetation was the only landcover type predicted to expand its distributional range. The range contractions predicted for other categories were intense, even suggesting extirpation of the sparse vegetation category. The landcover refuges under future climate change represent a small proportion of the South American area and they are disproportionately represented and unevenly distributed, predominantly occupying five of 26 South American countries. The predicted changes, regardless of their direction and intensity, can put biodiversity at risk because they are expected to occur in the near future in terms of the temporal scales of ecological and evolutionary processes. Recognition of the threat of climate change allows more efficient conservation actions.


Light-powered soft steam engines for self-adaptive oscillation and biomimetic swimming.
Oscillation plays a vital role in the survival of living organisms in changing environments, and its relevant research has inspired many biomimetic approaches to soft autonomous robotics. However, it remains challenging to create mechanical oscillation that can work under constant energy input and actively adjust the oscillation mode. Here, a steam-driven photothermal oscillator operating under constant light irradiation has been developed to perform continuous or pulsed, damped harmonic mechanical oscillations. The key component of the oscillator comprises a hydrogel containing Fe3O4/Cu hybrid nanorods, which can convert light into heat and generate steam bubbles. Controllable perturbation to the thermomechanical equilibrium of the oscillator can thus be achieved, leading to either continuous or pulsed oscillation depending on the light intensity. Resembling the conventional heat steam engine, this environment-dictated multimodal oscillator uses steam as the working fluid, enabling the design of self-adaptive soft robots that can actively adjust their body functions and working modes in response to environmental changes. An untethered biomimetic neuston-like robot is further developed based on this soft steam engine, which can adapt its locomotion mechanics between uniform and recurrent swimming to light intensity changes and perform on-demand turning under continuous light irradiation. Fueled by water and remotely powered by light, this unique hydrogel oscillator enables easy control over the oscillation dynamics and modes, offering an effective approach to self-adaptive soft robots and solar steam engines.


Short form MMPIs in medical consultation accuracy of the Hs-Hy dyad compared to the standard form.
Rescored 114 MMPIs of back pain patients, using the FAM and MMPI-168 method to determine whether the Hs-Hy dyad of individual profiles fell into designated diagnostic brackets consistent with the standard form MMPI. The specified categories were T scores greater than 75, T scores between 65-74, T scores less than 65. Overall efficiency for both the FAM and the 168 was 66%. For the extreme scores the efficiency of both short forms ranged from 69 to 85%, but in the moderate range (65-74 T) efficiency fell to 21% and 30% for the FAM and 168, respectively. Differences between the two short forms were non-significant at all levels. Use of short form MMPIs where individual profile analysis is required in medical consultation is discouraged.


The dose of nicorandil in men predicted from the inhibition of MAO activity by organic nitrates.
The effect of N-(2-hydroxyethyl)-nicotinamide nitrate ester (nicorandil) on rat heart monoamine oxidase (MAO) was investigated in vitro. MAO activity was assayed by the isotopic method with 14C-tryptamine as substrate. Nicorandil significantly inhibited MAO activity of rat heart mitochondria. The effect of nicorandil on the enzymatic kinetics of MAO of rat heart mitochondria indicates that the anti-anginal drug acts as a competitive inhibitor of MAO. The inhibitor constant (Ki) of nicorandil was 4.93 mmol/l. The Ki of nicorandil was fitted to the formula derived from the relationship between the Ki values of glyceryl trinitrate, erythrytol tetranitrate, mannitol hexanitrate and isosorbide dinitrate and the dose of these drugs recommended to relieve anginal pain in patients. The dose of nicorandil was 0.071 mmol (15.0 mg at a time). This value agreed with the clinical dose for patients (10--20 mg at a time).


Enhanced oxidative killing of azole-resistant Candida glabrata strains with ERG11 deletion.
The susceptibility of genetically defined Candida glabrata strains to killing by H2O2 and neutrophils was assessed. Fluconazole-susceptible L5L and L5D strains demonstrated survival rates higher than those of two fluconazole-resistant strains lacking the ERG11 gene coding for 14 alpha-demethylase. Fluconazole resistance can occur by mechanisms which increase fungal susceptibility to oxidative killing by H2O2 and neutrophils.


The pulmonary vascular complications of hereditary haemorrhagic telangiectasia.
Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder, characterised by the presence of vascular malformations. The pulmonary vascular complications of HHT include pulmonary arteriovenous malformations, pulmonary hypertension associated with high-output heart failure and liver vascular malformations and, finally, pulmonary arterial hypertension secondary to HHT. In the present review, the authors describe the clinical presentation, diagnosis and management of all three pulmonary vascular presentations of HHT, as well as the underlying genetics and pathophysiology.


Adenosine A(2A) receptor facilitation of hippocampal synaptic transmission is dependent on tonic A(1) receptor inhibition.
Adenosine tonically inhibits synaptic transmission through actions at A(1) receptors. It also facilitates synaptic transmission, but it is unclear if this facilitation results from pre- and/or postsynaptic A(2A) receptor activation or from indirect control of inhibitory GABAergic transmission. The A(2A) receptor agonist, CGS 21680 (10 nM), facilitated synaptic transmission in the CA1 area of rat hippocampal slices (by 14%), independent of whether or not GABAergic transmission was blocked by the GABA(A) and GABA(B) receptor antagonists, picrotoxin (50 microM) and CGP 55845 (1 microM), respectively. CGS 21680 (10 nM) also inhibited paired-pulse facilitation by 12%, an effect prevented by the A(2A) receptor antagonist, ZM 241385 (20 nM). These effects of CGS 21680 (10 nM) were occluded by adenosine deaminase (2 U/ml) and were made to reappear upon direct activation of A(1) receptors with N(6)-cyclopentyladenosine (CPA, 6 nM). CGS 21680 (10 nM) only facilitated (by 17%) the K(+)-evoked release of glutamate from superfused hippocampal synaptosomes in the presence of 100 nM CPA. This effect of CGS 21680 (10 nM), in contrast to the isoproterenol (30 microM) facilitation of glutamate release, was prevented by the protein kinase C inhibitors, chelerythrine (6 microM) and bisindolylmaleimide (1 microM), but not by the protein kinase A inhibitor, H-89 (1 microM). Isoproterenol (30 microM), but not CGS 21680 (10-300 nM), enhanced synaptosomal cAMP levels, indicating that the CGS 21680-induced facilitation of glutamate release involves a cAMP-independent protein kinase C activation. To discard any direct effect of CGS 21680 on adenosine A(1) receptor, we also show that in autoradiography experiments CGS 21680 only displaced the adenosine A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentyladenosine ([(3)H]DPCPX, 0.5 nM) with an EC(50) of 1 microM in all brain areas studied and CGS 21680 (30 nM) failed to change the ability of CPA to displace DPCPX (1 nM) binding to CHO cells stably transfected with A(1) receptors. Our results suggest that A(2A) receptor agonists facilitate hippocampal synaptic transmission by attenuating the tonic effect of inhibitory presynaptic A(1) receptors located in glutamatergic nerve terminals. This might be a fine-tuning role for adenosine A(2A) receptors to allow frequency-dependent plasticity phenomena without compromising the A(1) receptor-mediated neuroprotective role of adenosine.


A simple fluorescent technique for the location of tumour cells in frozen sections of the head and neck region.
Tumour cells possess cell surface proteases referred to as guanidinobenzoatase (GB) which are closely similar to plasminogen activator. Previous studies have demonstrated different isoenzymic forms of GB on tumour cells and normal cells which can be recognised by cytoplasmic protein inhibitors extracted from frozen sections of appropriate tissues. We now show that normal human serum possesses inhibitors which selectively recognise the isoenzymic forms of GB associated with normal cell surfaces but do not recognise the GB on tumour cell surfaces in frozen sections of tissue obtained from the head and neck regions.


[Current problems in the morphometry of the heart].
Cardiac morphometric data reported by different authors are difficult to compare. For linear measurements the processing methods need to be standardized and important considerations are the age-thanatogenetic features, and homogeneity of the autopsy material. An essential requirement is determination of the tissue compression coefficient. The specific volumes of structures should be measured in semithin sections. The largest disagreement among measurements have been noted for volumes of cardiac muscle cells and nuclei and for the nucleocytoplasmic ratio. The rules of stereometry are frequently violated in calculating parameters per unit sectional area. Although more than a hundred parameters have been proposed for cardiac morphometry, only two or three of them are of real diagnostic value. Standardizing morphometry of the heart, and of other organs as well, is a matter of high priority.


Synthetic tracked aperture ultrasound imaging: design, simulation, and experimental evaluation.
Ultrasonography is a widely used imaging modality to visualize anatomical structures due to its low cost and ease of use; however, it is challenging to acquire acceptable image quality in deep tissue. Synthetic aperture (SA) is a technique used to increase image resolution by synthesizing information from multiple subapertures, but the resolution improvement is limited by the physical size of the array transducer. With a large F-number, it is difficult to achieve high resolution in deep regions without extending the effective aperture size. We propose a method to extend the available aperture size for SA-called synthetic tracked aperture ultrasound (STRATUS) imaging-by sweeping an ultrasound transducer while tracking its orientation and location. Tracking information of the ultrasound probe is used to synthesize the signals received at different positions. Considering the practical implementation, we estimated the effect of tracking and ultrasound calibration error to the quality of the final beamformed image through simulation. In addition, to experimentally validate this approach, a 6 degree-of-freedom robot arm was used as a mechanical tracker to hold an ultrasound transducer and to apply in-plane lateral translational motion. Results indicate that STRATUS imaging with robotic tracking has the potential to improve ultrasound image quality.


Unreliability of contemporary neurodiagnostic imaging in evaluating suspected adult supratentorial (low-grade) astrocytoma.
Many physicians rely upon neuroimaging studies alone to select therapy for adult patients suspected of having a glial neoplasm, in the belief that certain imaging features accurately characterize the histological diagnosis of low-grade astrocytoma. During a 4-year interval when both computerized tomography and magnetic resonance imaging was available, the authors performed stereotactic biopsies on 20 consecutive adult patients who were suspected of having an astrocytoma. The patients were generally young (mean age 37 years), had seizures (17 cases), and had lobar lesions. An accurate histological diagnosis was obtained, without morbidity, in all 20 patients. Only 10 (50%) in fact had low-grade astrocytomas, whereas nine (45%) had anaplastic astrocytomas and one (5%) had encephalitis. The results of this study indicate that modern high-resolution neuroimaging alone cannot be used as a reliable tool to predict the histological diagnosis of astrocytoma (50% false-positive rate). All patients with supratentorial mass lesions that exhibit the "typical" imaging features of astrocytoma should undergo stereotactic biopsy for confirmation in order that appropriate management may be planned.


Bronchial artery embolization: first-line option for managing massive hemoptysis.
Background Today, treatment for hemoptysis is not limited to surgery, and among the various options, bronchial artery embolization is regarded as an effective approach. Methods In this retrospective study, 179 of 389 patients with massive hemoptysis were treated with bronchial artery embolization, without taking into account the underlying pathological lesions responsible (bronchiectasis in 41, aspergilloma in 29, lung cancer in 25, old tuberculosis in 23, pyothorax in 19, others in 23). Results Bronchial artery embolization failed in 12 cases. In the 167 successful cases, surgery was required in 16 and bronchial occlusion was performed in 4; 3 patients died due to recurrent massive hemoptysis. After bronchial artery embolization, thoracic surgery for reasons other than hemostasis was carried out in 15 patients. Bronchial artery embolization was performed in 31 patients with hemoptysis who had a history of chest surgery. Four patients underwent bronchial occlusion, and immediate hemostasis was achieved in all of them. Conclusions For treatment of hemoptysis, bronchial artery embolization is a safe and minimally invasive technique that can be performed repeatedly, and provides not only short-term but also prolonged effectiveness; thus it can be used as a first-line treatment irrespective of the underlying pathological lesion. Bronchial occlusion may be useful for emergency hemostasis, but it warrants careful follow-up with consideration of additional elective treatment such as bronchial artery embolization.


Molecular screening of Clostridium difficile toxins A and B genetic determinants and identification of mutant strains.
Three separate sets of polymerase chain reaction primers were designed to specifically detect the presence of a toxin A gene fragment, a toxin B gene fragment, and the entire toxin B gene. In addition toxin gene fragments that were amplified from well characterized toxic strains were tagged fluorescently and used as hybridization probes to screen C. difficile strains. A survey of 37 toxic strains and 10 non-toxic strains demonstrated that toxic strains normally contain the genetic composition for toxin A and toxin B simultaneously; whereas, non-toxic strains typically did not contain detectable toxin determinants. The only exception found was strain 39, which had the genetic composition for toxins A and B, but was not cytotoxic under the conditions tested.