Biological and pharmacological effects of hexahydrocurcumin, a metabolite of curcumin.
Curcumin, one of the most precious pharmacologically relevant natural products, has gained considerable attention among scientists for decades because of its multi-pharmacological activities in the clinical. However, critical studies on its pharmacological and toxicological activities are needed to understand how this compound can have these biological functions considering its poor oral bioavailability and the low plasma concentration. Moreover, curcumin undergoes extensive and rapid metabolism in vivo, indicating that the pharmacological activity of consuming curcumin might be mediated partly by its metabolites. And as one of the major curcumin metabolites, hexahydrocurcumin (HHC), exhibits similar or more potent bioactivity than curcumin by in vitro and in vivo studies, such as antioxidant, anti-inflammatory, antitumor and cardiovascular protective properties, which may provide important information for us to have a profound comprehension of the effectiveness of curcumin. This review mainly summarizes the current knowledge and underlying molecular mechanisms of the biological activities of HHC and its potential effects on the development of various human diseases.


Neuroendocrine changes post myocardial infarction: effects of xamoterol.
This study reports the effects of the new beta 1 adrenoceptor partial agonist, xamoterol, on neuroendocrine activity after acute myocardial infarction (AMI). Fifty-one consecutive patients with AMI were randomized to treatment with xamoterol, 200 mg twice a day, or placebo; patients were also stratified as to whether or not diuretic therapy was given for left ventricular dysfunction. Noradrenaline, plasma renin activity (PRA), and atrial natriuretic factor (ANF) were measured over a 10-day period. Noradrenaline concentrations are higher (p less than 0.05) in patients treated with diuretics at the time of admission and fell over the subsequent 10 days (p less than 0.01). Treatment with xamoterol did not affect this noradrenaline response to myocardial infarction. PRA was also significantly higher in the patients treated with diuretics, and there was a nonsignificant trend for xamoterol to blunt the PRA response in these patients. There was no difference in ANF levels between those patients who were treated with diuretics and those who were not; xamoterol did not affect ANF. Thus xamoterol does not further elevate noradrenaline levels as do conventional beta blockers, and it does not activate the renin-angiotensin system as do potent nonselective beta agonists. Furthermore, xamoterol does not increase ANF levels, probably because it is not negatively inotropic. We conclude that xamoterol does not cause deleterious neuroendocrine changes in patients with AMI even in those treated for heart failure.


Endothelialization of crosslinked albumin-heparin gels.
Crosslinked gels of albumin as well as heparinized albumin gels, potential sealants of prosthetic vascular grafts, were studied with regard to in vitro stability, binding of basic fibroblast growth factor (bFGF) and cellular interactions. A small percentage of the heparin present in these gels, was released during storage in SDS solution. During storage in cell culture medium at 37 degrees C, heparin release was 21-25 percent. Release of albumin did not occur. Human umbilical vein endothelial cells (HUVECs) rapidly adhered and subsequently spread on (heparinized) albumin gels, but proliferation was only observed if heparin was present in the gel. Binding of 125I-bFGF to heparinized albumin gel was 35 percent higher than to non-heparinized albumin gel. Growth of HUVECs occurred only on heparinized albumin gel loaded with bFGF and not on bFGF-loaded albumin gel. The number of platelets deposited under stationary conditions onto heparinized albumin gel was about twice the number found on nonheparinized albumin gel. Seeding of HUVECs on heparinized albumin gel, significantly reduced the number of platelets adhering to this surface. Moreover, no spreading of platelets was observed on substrates seeded with HUVECs. It can be concluded that crosslinked gels of albumin to which heparin is immobilized, are candidate sealants for prosthetic vascular grafts and suitable substrates for endothelial cell seeding.


Quartz crystal biosensor for real-time monitoring of molecular recognition between protein and small molecular medicinal agents.
A quartz crystal microbalance (QCM) biosensor integrated into a flow injection analysis (FIA) system was used for the real-time investigation of molecular recognition between a protein and small molecular medicinal agents. Two sulfa-drugs, sulfamethazine (SMZ) and sulfamethoxazole (SMO), were, respectively, immobilized on the gold electrodes of the piezoelectric crystals using appropriate procedures based on self-assembly of the dithiothreitol (DTT). The binding interactions of the two immobilized drug ligands, with various proteins in solution, were followed as changes in the resonant frequency of the modified crystals. Results obtained from this rapid screen analysis clearly indicated that the two drug ligands appeared quite different in this molecular recognition procedure although their structures were similar. SMZ-immobilized sensor showed specific interaction only with IgG, while SMO-immobilized sensor showed negligible specific binding with IgG, but binding with trypsin and chymotrypsin. Further studies on the specific interaction between immobilized SMZ and three different species of IgG--human IgG, goat IgG and mouse IgG were carried out and the marked species-dependent difference was observed. The resultant sensorgrams were rapidly analyzed by using an in-house kinetic analysis software based on genetic algorithm (GA) to derive both the kinetic rate constants (kass and kdiss) and equilibrium association constants (KA) for IgG-SMZ interactions. For the interactions, KA were 5.48 x 10(5), 2.75 x 10(5) and 1.86 x 10(5) M(-1) for human IgG, goat IgG and mouse IgG, respectively. The kinetic data provided further insight into the structural/functional relationships of different IgG on a molecular level.


Effect of cryopreservation of zona-binding capacity of canine spermatozoa in vitro.
The hemizona assay (HZA) was used as a functional test for zona pellucida binding capacity of fresh and frozen-thawed canine spermatozoa. We investigated 30 ejaculates from 3 dogs with sperm motility > 70% and sperm concentration > 5.10(8) cells per ejaculate with up to 20% abnormal and dead spermatozoa. Fifteen ejaculates were each divided into 2 portions: one portion was used for analysis of fresh semen, the other for cryopreserved semen. On the day of the experiments, in vitro-matured canine oocytes were bisected into 2 equal hemizonae. One half of the hemizonae were coincubated with fresh capacitated (control) spermatozoa, the other half of the hemizonae were coincubated with frozen-thawed (tested) spermatozoa at final concentration of 1 to 2 x 10(6) cells/mL in 200 microL droplets of BSA-supplemented Toyoda, Yokojama and Hoshi (TYH) medium at 37 degrees C, 5%, CO2 for 1 h. Sperm suspensions were examined kinesigraphically for post capacitation type of movement. The Student's t-test was used to compare differences between semen parameters. The data on HZA binding activity of fresh and frozen-thawed canine semen were analyzed by ANOVA and then by the Newman-Keuls multiple range method. The results showed no differences in the initial semen quality parameters among the 3 dogs. After thawing, the semen from Dog 1 and Dog 2 demonstrated relatively uniform sperm parameters, while in Dog 3 sperm motility, and viability and the percentage of morphologically normal spermatozoa were significantly decreased. The binding activity of frozen-thawed spermatozoa from the 3 dogs was significantly reduced (29.40 +/- 9.02, 18.60 +/- 3.30, 8.20 +/- 4.49) compared with that (107.20 +/- 19.22, 109.80 +/- 20.75, 78.20 +/- 12.47; P < 0.01) of fresh spermatozoa. The results showed that semen samples with similar sperm parameters prior to cryopreservation displayed different sperm zona-binding capacity after freezing. The HZI (value of sperm binding capacity of frozen-thawed vs fresh semen samples) was higher in Dog 1 (27.43) than in Dog 2 (16.90) or Dog 3 (10.40), and thus confirmed the variation of zona binding activity after thawing between dogs. The freezability of individual dog semen is discussed. In conclusion HZA may be a valuable tool for evaluating the post-thaw fertilizing ability of canine spermatozoa.


Enhancing the decoding performance of optical wireless communication systems using receiver-side predistortion.
White light emitting diodes (LEDs) have been widely utilized for illumination owing to their desired properties of inherent bright output, high efficiency, low power consumption and long life-time. They are also increasingly applied in optical wireless communications for realizing high data rate transmission. This paper presents an improved scheme relying on the insertion of a simple predistortion module before the decoder at the receiver of optical wireless communication systems that use white LEDs. The proposed predistortion scheme exploits the inherent nature of mixing the three unequal optical-power primary colours in generating white light to enhance the system's performance. Specifically, we design this predistortion module by minimizing the upper bound of the error probability in conjunction with a soft-decision decoder. Our simulation results demonstrate that the detection performance is considerably improved with the aid of the proposed predistortion module.


[Determination of lactoferrin in the diagnosis of pancreatopathy in patients with chronic kidney failure].
The authors investigated in patients with renal disease the lactoferrin content in duodenal aspirate. The aspirate was obtained after previous stimulation of the pancreas with pancreozymin. Lactoferrin estimation is described in the literature as a sensitive examination of changes of exocrine pancreatic secretion. The authors provided evidence that by assessing lactoferrin it is possible to detect initial changes of reduced exocrine pancreatic capacity already in subjects who are on the waiting list of chronic intermittent haemodialyzation programmes (CHIDP); maximum increase of the lactoferrin content in the duodenal aspirate corresponds with the severity of chronic renal failure. Transplantation of the kidneys leads to normalization of the amount of lactoferrin secreted by the pancreas which is evidence of normalization of pancreatic secretion. In patients with chronic renal failure lactoferrin is a sensitive marker of developing uraemic pancreatopathy.


Mixed ligand complexes involving sulphur containing ligands--Part II. Ternary complexes of Zn(II) involving L-cysteine/D-penicillamine/L-cysteic acid and imidazoles.
The chemical equilibria involved in nine mixed ligand systems Zn(II)-L-cysteine (Cys)/D-penicillamine(Pen)/L-cysteic acid(Cya)(A)-imidazole(Him), histamine(Hist) and L-histidine(His)(B) have been investigated in aqueous perchlorate medium by pH titrimetry at 37 degrees and ionic strength, I = 0.15M (NaClO(4)). The mixed ligand complex species of the types ZnABH(2), ZnABH, ZnAB or ZnAB(2) have been detected in addition to various binary species due to ligands A and B. The results obtained for the ZnABH type of species indicate that the site of protonation is the amino group of Cys/Pen ligands in the Zn(II)-Cys/Pen(A)-Him, Hist and His(B) systems, and the amino group of Hist/His secondary ligands in the Zn(II)-Cya(A)-Hist and His(B) systems. In the ZnABH(2) type of species, one proton is attached with the primary ligand (A) and the other with the secondary ligand(B). In both ZnAB and ZnAB(2) type ternary species in all the systems, the primary ligand binds the metal in a bidentate manner and the secondary ligands Him, Hist and His bind the metal, respectively in a uni, bi and terdentate manner.


Systemic nitroglycerin activates peptidergic and catecholaminergic pathways in rat brain.
In this study, we carried out an immunohistochemical evaluation of the neurochemical characteristics of neurons that are activated (i.e., express Fos protein) in response to systemic administration of nitroglycerin. In the brain stem, a significant percentage of activated neurons contained noradrenaline as a neurotransmitter, whereas only a few of them contained serotonin. In the paraventricular and supraoptic nuclei of the hypothalamus, numerous Fos-immunoreactive neurons were also positive for vasopressin, oxytocin, and corticotropin-releasing factor. Codistribution with corticotropin-releasing factor was also observed in the central nucleus of the amygdala. Our findings point out a prominent role for catecholaminergic and peptidergic pathways in the brain in response to systemic nitroglycerin.


[Changes in the activity of angiotensin converting enzyme in the structures of the rat brain after frontal lobectomy].
The functional state of the angiotensin system (the activity of the angiotensin converting enzyme--ACE) was studied in different rat brain regions during disturbance of the integrative activity of CNS after frontal lobectomy. The most prominent increase of the ACE activity (in four times) on the ninth day after lobectomy was detected in crown cortex and hippocamp. Considerable differences were discovered in striatum, thalamus and hypothalamus also. The variations of the ACE activity were not shown in the medulla oblongata and midbrain. It is possible to conclude, that ACE activity alternations have regional disposition and functional dependence.


Transgene constructs lacking transcription termination signal induce efficient silencing of endogenous targets in Arabidopsis.
Efficient gene silencing tools are extremely important for genomics and biotechnology applications. A number of aberrant RNA species induce silencing of homologous genes; however, only the inverted repeat RNA is widely utilized for targeted gene silencing in plants. Development of additional silencing constructs would not only provide an alternative technology for single targets, it may also serve as a simpler platform for multi-target silencing. The present study found that aberrantly terminated sense transcripts serve as efficient inducers of gene silencing. A construct initially designed to carry out homologous recombination into the Phytochrome A locus of Arabidopsis induced instead a high rate of Phytochrome A silencing, resulting in a strong mutant phenotype. Attempts to decipher the silencing determinant of the construct revealed that absence of a proper transcription termination signal contributed to the silencing efficiency of the construct. Furthermore, silencing of an additional gene, Phytochrome B, was conferred by a separate construct of a similar design. Proper placement of a transcription termination signal in the silencing construct abolished its silencing ability. Therefore, transcription of aberrantly terminated transcripts was deduced to be the cause of the elevated rate of silencing observed in transgenic lines. These transcripts could be produced either by direct transcription or read-through transcription. Since silencing resulted in strong mutant phenotypes in the majority of transgenic lines, terminator-less constructs are proposed to serve as efficient tools for knocking out endogenous targets.


Cannabinols and feeding in sheep.
Marijuana, long used for the euphoria which results, recently has been found to stimulate hunger in humans but in several laboratory animals cannabinoids decrease food intake. Sheep, relatively more sensitive to chemicals that affect food intake, were injected IV with the d-and l-isomers of tetrahydrocannabinol and with a 9-aza-cannabinol) 9-AC) (8-(1,2-dimethylheptyl)-5,5-dimethyl-5H-[1]benzopyranol[3,4]pyridin-10-01, HCL) and feeding behavior was monitored. In the first 30 min, food intake was increased by the l-isomer and by 9-AC but not affected by d-delta 9-THC. After 24 h, feed intake was decreased by at least one dose of d-and l-delta 9-THC and 9-AC. The l-but not d-isomer was active at very low doses compared with doses used in many laboratory animals.


Traffic-related air pollution exposure is associated with allergic sensitization, asthma, and poor lung function in middle age.
Traffic-related air pollution (TRAP) exposure is associated with allergic airway diseases and reduced lung function in children, but evidence concerning adults, especially in low-pollution settings, is scarce and inconsistent. We sought to determine whether exposure to TRAP in middle age is associated with allergic sensitization, current asthma, and reduced lung function in adults, and whether these associations are modified by variants in Glutathione S-Transferase genes. The study sample comprised the proband 2002 laboratory study of the Tasmanian Longitudinal Health Study. Mean annual residential nitrogen dioxide (NO2) exposure was estimated for current residential addresses using a validated land-use regression model. Associations between TRAP exposure and allergic sensitization, lung function, current wheeze, and asthma (n = 1405) were investigated using regression models. Increased mean annual NO2 exposure was associated with increased risk of atopy (adjusted odds ratio [aOR], 1.14; 95% CI, 1.02-1.28 per 1 interquartile range increase in NO2 [2.2 ppb]) and current wheeze (aOR, 1.14; 1.02-1.28). Similarly, living less than 200 m from a major road was associated with current wheeze (aOR, 1.38; 95% CI, 1.06-1.80) and atopy (aOR, 1.26; 95% CI, 0.99-1.62), and was also associated with having significantly lower prebronchodilator and postbronchodilator FEV1 and prebronchodilator forced expiratory flow at 25% to 75% of forced vital capacity. We found evidence of interactions between living less than 200 m from a major road and GSTT1 polymorphism for atopy, asthma, and atopic asthma. Overall, carriers of the GSTT1 null genotype had an increased risk of asthma and allergic outcomes if exposed to TRAP. Even relatively low TRAP exposures confer an increased risk of adverse respiratory and allergic outcomes in genetically susceptible individuals.


The genus Crataegus L.: an ecological and molecular study.
This study aimed at the indentification of the species and genotypes of the genus Crataegus in Syria and determination of the genetic relationships among them based on the analysis of genomic and chloroplast DNA (cpDNA) using ISSRs and CAPS techniques. Morphological characterization carried out on 49 Crataegus samples collected from different geographical regions of Syria revealed four Crataegus species: C. monogyna, C. sinaica, C. aronia and C. azarolus. In the dendrogram constructed for those samples based on ISSRs (20 primers), all samples that belong to C. monogyna were clustered in one cluster. Samples of the other three species were overlaped in another cluster. Two samples of these were the most distant from all other samples in the dendrogram and were suggested to represent hybrid species or subspecies. When CAPS technique was applied on four Crataegus samples that represent the four suggested species using 22 cpDNA regions and 90 endonucleases, no polymorphism was detected neither in amplification products sizes nor in restriction profiles. The inability of detection of variation in cpDNA among species suggested can be attributed to the low level of evolution of the cpDNA in the genus, and to the possibility that some of these species are either subspecies or hybrids since the cpDNA is inherited through one parent only.


Restricted pH ranges and reduced yields for bacterial growth under pressure.
Hydrostatic pressure was found to cause a marked narrowing of pH ranges for growth and reductions in growth yields for a variety of bacteria. In many cases, reduced yields under pressure could be directly related to increased sensitivities to metabolic acids that accumulated in the enclosed culture vessels used. Magnesium and calcium ions partially reversed increases in sensitivities of representative gram-positive and gram-negative bacteria to low, but not high, pH. Growth inhibition of these organisms at both extremes of pH was associated with enhanced loss of K(+) from pressurized cells. Inhibited cells in alkaline media also lysed under pressure, but microscopically observable lysis was clearly a secondary phenomenon because it occurred slowly. Apparent volumes for growth-inhibitory protonation-deprotonation reactions were calculated on the basis of measured shifts in inhibitory pH with pressure. The values ranged from 99 to 431 ml/mole, and their magnitudes indicated that growth inhibition by acids or bases involves cooperative changes in polymeric interactions such as those which accompany protein denaturation.


Empirical validation and the importance of testable theory: a paradigm shift in psychotherapy?
In response to the recent special issue of the American Journal of Clinical Hypnosis (Vol. 54, No. 4, "Cognitive Hypnotherapy: Twenty Years Later"), this commentary discusses: (1) the weak connection between cognitive science and cognitive behavioral therapy, and (2) the importance of coherent and testable theoretical underpinnings to the practice of psychotherapy. The author briefly introduces Relational Frame Theory (RFT), which postulates that strategies to control, manage, or extinguish language based internal experience are unlikely to be successful. Acceptance Commitment Therapy (ACT) is a mindful and acceptance based empirically supported approach to creating client psychological flexibility. ACT underpinned by RFT is suggestive of a paradigm shift in psychotherapy to a mindfulness and acceptance approach to internal experience.


N-heterocyclic carbene catalyzed ring expansion of 4-formyl-beta-lactams: synthesis of succinimide derivatives.
N-heterocyclic carbene (NHC) has been employed as an efficient catalyst for ring expansion of 4-formyl-beta-lactams, allowing the facile synthesis of succinimide derivatives. This organocatalytic process features readily availability of the catalyst, low catalyst loading, and mild reaction conditions.


Expression of hyaluronan in benign and malignant breast lesions.
Hyaluronan (HA) is one of the extracellular-matrix components involved in wound healing, tumour growth and metastasis. Due to the limited data on HA expression in benign and malignant breast lesions, we analyzed its presence in these lesions by using the biotinylated-hyaluronan-binding region and the link-protein complex (bHABC) of cartilage proteoglycan as a specific probe. In all benign breast lesions, the expression of HA was restricted to the stromal connective tissue, the ductal epithelial cells being completely devoid of HA. In malignant breast tumours, the intensity of stromal HA staining was significantly stronger than in benign lesions. In addition, HA was detected on cell membranes or in cytoplasms of adenocarcinoma cells, in some cases of ductal carcinoma in situ and in 31% of malignant tumours. The staining pattern was mostly similar in all breast-cancer types studied, i.e., ductal, lobular, tubular, mucinous and medullary. In ductal breast cancer, intense HA expression in stroma and carcinoma cells correlated statistically significantly to poor differentiation of carcinoma, suggesting that altered HA expression may affect the mechanisms of breast-cancer progression.


The ETO domain is necessary for the developmental abnormalities associated with AML1-ETO expression in the hematopoietic stem cell compartment in vivo.
Translocation of the ETO gene on human chromosome 8 with the AML1 gene on chromosome 21 (AML1-ETO) is a recurrent cytogenetic abnormality associated with approximately 12% of acute myelogenous leukemia (AML) cases. To understand the contribution of the t(8;21) to AML, we transduced purified hematopoietic stem cells (HSC) with a retroviral vector that coexpressed AML1-ETO or just the AML1 portion (AML1d) of the translocation along with a green fluorescent protein reporter gene. Animals reconstituted with AML1-ETO-expressing cells exhibited many of the hematopoietic developmental abnormalities seen in the bone marrow of human patients with the t(8;21), although the animals did not develop acute leukemia. We noted a gradual increase in primitive myeloblasts that accounted for approximately 10% of bone marrow by 10 months posttransplant. Consistent with this observation was a 50-fold increase in myeloid colony-forming cells in vitro. In addition, accumulation of late stage metamyelocytes was observed in bone marrow along with an increase in immature eosinophil myelocytes that showed abnormal basophilic granulation. There was also a gradual increase in both the frequency and absolute number of AML1-ETO-expressing HSC so that by 10 months posttransplant, there were 29-fold greater HSC numbers than in transplant-matched control mice. These phenotypes were not observed in animals reconstituted with cells expressing only the DNA-binding domain of AML1, suggesting that the ETO domain is necessary to establish the developmental abnormalities associated with AML1-ETO expression in HSC.


Heterogeneity of breast cancer risk in families of young breast cancer patients and controls.
Familial heterogeneity of breast cancer risk was assessed among 4,159 first-degree female relatives of 1,074 population-based, young breast cancer cases (aged 20-54 years) diagnosed from December 1, 1980 to December 31, 1982 and 4,120 first-degree female relatives of 998 age- and race-matched, population-based controls from the metropolitan Detroit, Michigan, area. The family risk index method used for analysis considers family size, age, and race differences among families in the assessment of family risk. Families of cases showed a higher risk of breast cancer than did families of controls, with case families 1.80 to 4.24 times more likely to be defined as high risk than control families; the magnitude of the risk differential was dependent on the definition of high risk. Within the case families only, familial heterogeneity of risk was suggested, with a small proportion of families (less than 5%) at lower risk of breast cancer than most case families. A number of reproductive risk factors, age, race, and histologic type of cancer for the proband, and several family characteristics were investigated to help characterize the case families at higher and lower risk.


Evaluation of syncope.
Syncopal episodes are relatively common. A variety of etiologies can underlie syncope, and the cause is often multifactorial. A thorough history and a complete physical examination are essential initial components in the evaluation of a patient with syncope. Prodromal symptoms often accompany fainting of vasovagal origin, while the occurrence of syncope without warning in a patient with cardiac problems suggests arrhythmia. Many medications, including antihypertensives, antidepressants and digitalis, may be responsible for episodes of fainting. The physical examination of a patient with a history of syncope includes measurement of orthostatic blood pressure, as well as careful cardiovascular and neurologic evaluations. The decision to use ancillary laboratory and electrocardiographic testing is guided by the patient's history and the findings on physical examination. Although new technologies, such as loop electrocardiography and tilt table tests, can aid in the diagnosis of syncope, they should not be used routinely.


Clinical evaluation of the Abbott RealTime MTB Assay for direct detection of Mycobacterium tuberculosis-complex from respiratory and non-respiratory samples.
Rapid and reliable diagnosis is crucial for correct management of tuberculosis. The Abbott RealTime MTB Assay represents a novel qualitative real-time PCR assay for direct detection of M. tuberculosis-complex (MTB) DNA from respiratory samples. The test targets two highly conserved sequences, the multi-copy insertion element IS6110 and the protein antigen B (PAB) gene of MTB, allowing even the detection of IS6610-deficient strains. We evaluated this commercial diagnostic test by analyzing 200 respiratory and, for the first time, 87 non-respiratory clinical specimens from our tertiary care institution and compared its results to our IS6110-based in-house real-time PCR for MTB as well as MTB culture. Overall sensitivity for Abbott RealTime MTB was 100% (19/19) in smear positive and 87.5% (7/8) in smear negative specimens, while the specificity of the assay was 100% (260/260). For both non-respiratory smear positive and smear negative specimens Abbott RealTime MTB tests showed 100% (8/8) sensitivity and 100% (8/8) specificity. Cycle threshold (Ct) value analysis of 16 MTB positive samples showed a slightly higher Ct value of the Abbott RealTime MTB test compared to our in-house MTB assay (mean delta Ct = 2.55). In conclusion, the performance of the new Abbott RealTime MTB Assay was highly similar to culture and in-house MTB PCR. We document successful analysis of 87 non-respiratory samples with the highly automated Abbott RealTime MTB test with no inhibition observed.


Ultrasound-guided percutaneous lavage of calcific bursitis of the medial collateral ligament of the knee: a case report and review of the literature.
Calcification of the medial collateral ligament (MCL) of the knee is rare. The literature reports no positive outcomes when conservative treatment has been followed. This paper reports a case of such calcification and its treatment using ultrasound-guided percutaneous lavage (UGPL). A 66-year-old patient presented with medial knee pain. X-ray, ultrasound, and magnetic resonance (MR) examinations revealed calcific bursitis of the MCL, which was treated by UGPL. One month after treatment the patient was asymptomatic. X-ray, ultrasound, and MR examinations confirmed the almost complete disappearance of the calcification; only very tiny fragments remained. Calcific bursitis of the MCL of the knee is very uncommon, but should be taken into account in differential diagnoses for medial knee pain. UGPL is proposed as a treatment for this condition.


Pooled versus separate tree-ring δD measurements, and implications for reconstruction of the Arctic Oscillation in northwestern China.
Stable hydrogen isotope ratios (δD) in tree rings are an attractive but still rarely explored terrestrial archive of past climatic information. Because the preparation of the cellulose nitrate for δD measurements requires more wood and a longer preparation time than preparation techniques for other isotopes in cellulose (δ18O or δ13C), it is challenging to obtain high-resolution records, especially for slow-growing trees at high elevations and in boreal regions. Here, we tested whether annually pooled samples of Qinghai spruce (Picea crassifolia Kom.) trees from northwestern China provided results similar to those derived as the mean of individual measurements of the same trees and whether the resulting chronologies recorded useful climate information. Inter-tree variability of δD was higher than that of measured ring width for the same trees. We found higher and significant coherence between pooled and mean isotope chronologies than that among the individual series. It showed a logarithmic relationship between ring mass and δD; however, accounting for the influence of ring mass on δD values only slightly improved the strength of climatic signals in the pooled records. Tree-ring δD was significantly positively correlated with the mean, maximum, and minimum temperatures during the previous winter and with maximum temperature during the current August, and significantly negatively correlated with precipitation in the previous November to January and the current July. The winter climate signal seems to dominate tree-ring δD through the influence of large-scale atmospheric circulation patterns, i.e. the Arctic Oscillation. These results will facilitate reconstruction of winter atmospheric circulation patterns over northwestern China based on a regional tree-ring δD networks.


Studies on the prevalence of type C virus associated with gibbon hematopoietic neoplasms.
Gibbon malignancy frequently involves the hematopoietic system and can occur in clusters. Virus isolated from gibbon neoplasms possessed typical type C virus morphology, and the virion measured 100 nm in diameter with an electron-dense nucleoid measuring approximately 75 nm. The virus incorporated 3H-uridine into the nucleic acid and rested at a buoyant density of 1.14-1.16 g/cm3. Intra-and interspecific antigenic determinants were present, and the intraspecific antigenic determinant was shared with the woolly monkey sarcoma virus but not with feline or murine type C viruses. The virus and antibody reactive to the virus are more prevalent in gibbon groups that experience leukemia than those free of hematopoietic neoplasms.


Detection of porcine circovirus type 2 in feces of pigs with or without enteric disease by polymerase chain reaction.
To establish the sensitive polymerase chain reaction(PCR) method and detect porcine circovirus type 2 (PCV2) from intestines and feces of commercial swine herds with or without enteric disease, intestinal samples from 68 pigs and 29 fecal samples from commercial swine farms were collected. A primer set, forward primer 5'-GAAGAATGGAAGAAGCGG-3' and reverse primer 5'-CTCACAGCAGTAGACAGGT-3', could detect the virus at a concentration as low as 2 infectious virions per milliliter under controlled conditions using PK-15 cell-adapted PCV2. The genomic nucleotide sequences of open reading frame 1 (ORF1) PCR products from fecal samples were found to have complete homology with other PCV2s deposited in the GenBank database. Transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) as the other enteric pathogens were also investigated by performing duplex reverse transcription-PCR (RT-PCR). Among 63 pigs with clinical enteric disease, 18 PCV2s (14 from intestines and 4 from feces), 7 TGEVs from intestines, and 18 PEDVs (14 from intestines and 4 from feces) were detected by PCR and the duplex RT-PCR. In 34 pigs (14 from intestines and 20 from feces) without clinical enteric disease, only PCV2 was detected in 19 pigs (3 from intestines and 16 from feces). Both PEDV and PCV2 were found in 6 pigs with clinical enteric disease. Among 15 PCV2 samples that were PCR-positive, 4 were culture-positive at passage level 3 in PK-15 cells. These results reveal that PCV2 is shed through the feces of pigs without clinical enteric disease, which suggests the potentiality of the fecal-oral transmission of PCV2 in feces.


Right origin of the circumflex artery and posterior aortic annulus enlargement.
We present the case of a patient who required posterior enlargement of the aortic annulus during aortic valve replacement in the presence of abnormal origin of the circumflex artery from the right coronary artery, with a retroaortic course.


p16 - a Possible Surrogate Marker for High-Risk Human Papillomaviruses in Oral Cancer?
High-risk human papillomaviruses (HR-HPV), particularly types 16 and 18, have been found to play an important role in head and neck cancer, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). p16, a cell cycle inhibitor, has been postulated as a surrogate marker for HR-HPV, since p16 is aberrantly overexpressed in such lesions, especially in HR-HPV-positive OPSCC. However, p16 as a surrogate marker for HR-HPV infection in cancers of the oral cavity remains controversial. The objectives of the study were to investigate the expression of p16 and the presence of HR-HPV in OSCC and oral verrucous carcinoma (VC) and to determine if p16 could be used as a surrogate marker for HR-HPV. Forty one formalin-fixed, paraffin-embedded tissues of OSCC (n=37) or VC (n=4) with clinical and histopathologic data of each case were collected. Expression of p16 was determined by immunohistochemistry, focusing on both staining intensity and numbers of positive cells. The presence of HPV types 16 and 18 was detected by polymerase chain reaction (PCR). Descriptive statistics were employed to describe the demographic, clinical, and histopathologic parameters. Associations between p16 overexpression, HR-HPV and all variables were determined by Fisher's exact test, odds ratios (ORs) and corresponding 95% confidence intervals (CIs). In addition, the use of p16 as a surrogate marker for HR-HPV was analyzed by sensitivity and specificity tests. p16 was overexpressed in 8/37 cases (21.6%) of OSCC and 2/4 cases (50%) of VC. HPV-16 was detected in 4/34 OSCC cases (11.8%) and HPV-18 was detected in 1/34 OSCC cases (2.9%). Co-infection of HPV-16/18 was detected in 1/4 VC cases (25%). Both p16 overexpression and HR-HPV were significantly associated with young patients with both OSCC and VC (<0.05, OR 20, 95% CI 1.9-211.8; <0.05, OR 23.3, 95% CI 2.4-229.7, respectively). p16 was able to predict the presence of HPV-16/18 in OSCC with 40% sensitivity and 79.3% specificity and in VC with 100% sensitivity and 66.7% specificity, respectively. p16 overexpression was found in 24.4% of both OSCC and VC. HR-HPV, regardless of type, was detected in 15.8% in cases of OSCC and VC combined. The results of sensitivity and specificity tests suggest that p16 can be used as a surrogate marker for HR-HPV in OSCC and VC.


Resin dental casts as an aid in bite mark identification.
Two techniques are presented for the fabrication of resin dental casts to aid in bite mark analysis. The first technique produces visible light cured dental casts of the suspected biter's dentition. These casts can be compared to the victim's bite marks or photographs of the bite marks. The technique is rapid and casts of the suspected biter's dentition can be made in less than thirty minutes, which is advantageous when the elimination of possible suspects must be accomplished in a timely fashion. The second technique involves the fabrication of crystal clear epoxy resin dental casts of the suspected biter's dentition. The dental casts are translucent and permit visualization through the teeth when comparisons are made to the bite marks or to tracings or photographs of the bite marks. The casts can also serve as an educational tool for a jury or juries in trials involving bite mark evidence. The resin dental casts are less brittle than dental stone casts permitting storage without concern for breakage for periods of years.


Survival of dietary antigens in the digestive tract of calves intolerant to soybean products.
Preruminant calves were given a series of feeds containing heated soybean flour. Digesta collected from the small intestine were analysed by haemagglutination inhibition assay for soluble soybean antigens. The presence of undenatured glycinin and beta-conglycinin in ileal contents was associated with digestive disturbances. In vitro experiments showed that, under optimal conditions of pH for protease activity, beta-conglycinin but not glycinin, was unaffected by pepsin and both antigens were resistant to rennin and trypsin. The solubility of glycinin and beta-conglycinin in saline extracts remained high over pH ranges of 2 to 3 and 6 to 10 but under conditions of intermediate pH, about 4.5, solubility was minimal. It was concluded that preruminant calves suffer from gastrointestinal hypersensitive responses to certain soybean products because major proteases of the digestive tract fail to denature soluble antigenic constituents of the soybean protein.


[Invasive amebiasis at an institution for the mentally retarded in Hyogo Prefecture].
An outbreak of amebiasis caused by Entamoeba histolytica occurred at an institution for mentally retarded persons in Hyogo Prefecture. Twelve out of a total of 49 admitted persons exhibited E. histolytica cysts in their stool, and 13 including persons in whom no cysts had been detected showed positive serological reactions for E. histolytica infection. However, neither the cyst nor the antibody against the organism was detected in the staff members of the institution. Indirect fluorescence antibody test and sandwich enzyme-linked immunosorbent assay with a monoclonal antibody specific for pathogenic strains of E. histolytica revealed that all trophozoite strains grown from cysts in stool samples from five patients were pathogenic. Epidemiological analysis strongly suggested that a patient in the institution had been infected with an organism from a patient outside the institution, and that infection may have spread among the admitted persons due to abnormal behavior. Administration of metronidazole resulted in effective elimination of the cysts from the stool of the cyst-carriers.


Upper airway muscle activity during REM and non-REM sleep of patients with obstructive apnea.
We measured electromyograms (EMGs) of genioglossus muscle (GG) and inspiratory intercostal muscle (IIM) in both rapid eye movement (REM) sleep and non-REM sleep of 12 patients with obstructive sleep apnea (OSA) to examine the influence of different sleep stages on upper airway muscle activity during sleep apnea. Quantifications of both muscle activities were assessed by their individual peak amplitude of integrated inspiratory EMG. Genioglossus and IIM activities showed a qualitatively similar cyclic change with an alteration of apneic and ventilatory phases during both non-REM and REM sleep. Both muscle activities increased gradually in the late apneic phase and reached each peak at the opening of the upper airway and, subsequently, decreased gradually. There were no significant differences in both muscles activities in either the ventilatory or early apneic phase between non-REM sleep and REM sleep. On the other hand, GG and IIM activities in the late apneic phase during REM sleep were significantly lower than those during non-REM sleep. The relative activity of GG to IIM in the late apneic phase was significantly lower during REM sleep than that during non-REM sleep. These results indicate that upper airway and intercostal muscle activation in the later apneic phase during REM sleep were inhibited compared with those during non-REM sleep and that this inhibition was observed predominantly in upper airway muscles.


Prognostic value of the preoperative neutrophil-lymphocyte ratio in patients undergoing the bidirectional Glenn procedure.
The neutrophil-lymphocyte ratio (NLR) has been associated with worse outcomes in patients undergoing coronary artery bypass graft surgery. Little is known about this association in the pediatric population who require surgery for congenital heart defects, especially in patients with a single ventricle (SV). To analyze the association of the preoperative NLR with outcomes in patients undergoing the bidirectional Glenn procedure. This study involved a retrospective cohort analysis of 141 consecutive patients with SV undergoing the bidirectional Glenn procedure between January 2011 and December 2017 in two centers. The preoperative NLR was included in the last hemogram test before surgery. According to the NLR level, the patients were divided into group I (NLR < 1), group II (NLR between 1 and 2), and group III (NLR > 2). The primary endpoint was total hospital length of stay (LOS), and secondary endpoints were mechanical ventilation (MV) time, intensive care unit (ICU) LOS, ventricular dysfunction, complications, and middle-term mortality. The average follow-up duration was 48 months. There were 61, 47, and 33 patients in groups I, II, and III, respectively. Patients in group III exhibited an increased risk of prolonged total hospital LOS (P = .00). An increase in MV time (P = .03) and ICU LOS (P = .02) was also observed in this group, and these patients experienced greater mortality in 24 months following the surgery (P = .03). There was no association between the NLR and ventricular dysfunction (P = .26) and complications (P = .46). A high preoperative NLR was associated with worse outcomes in patients with SV physiology undergoing the bidirectional Glenn procedure.


Consensus guidelines on quantifying HIV-related oral mucosal disease.
The workshop agreed that the development of consensus quantification protocols was desirable, but that this whole field was underdeveloped, to date. The working goals were therefore redefined (vide infra). Three possible protocols were presented and discussed relating to oral hairy leukoplakia, oral ulceration (NOS) and oral candidiasis. There was agreement that different data-set protocols would have to be developed for specific HIV-related mucosal diseases. Furthermore, the data set should be consistent, standardized and disaggregated. In this way, with everyone working to the same standards of outcome, data from geographically, nationally, socially or culturally different areas could be readily compared. A future meeting to generate the disease-specific protocols would, most likely, be needed.


Review article: A primer for clinical researchers in the emergency department: Part VIII. Implementation science: An introduction.
New research findings may not lead to change in practice, or a change at the front line may be delayed by years. A number of terms have been used to describe efforts and strategies to speed a change in evidence-based practice, such as: implementation science, knowledge translation, research translation and others. In contrast to traditional clinical research, implementation science generally aims to understand and change health professional behaviour to promote evidence uptake as opposed to attempting to change patient behaviour. There are now theoretical frameworks and evolving evidence providing guidance how to change clinician behaviour and, specifically, emerging evidence on how to achieve this in the emergency setting. This review will provide an introduction to implementation science and illustrate how to target evidence practice gaps using ED examples.


Exploration of the association of selected pain diagnoses with risky alcohol use among active duty soldiers.
Background: Pain and its consequences remain of concern, particularly in high-risk occupations such as the military. Alcohol is a legal and accessible means of self-medication, and risky alcohol use is associated with potentially serious consequences. This exploratory analysis aimed to better understand the association of selected pain diagnoses with risky alcohol use among soldiers returning from deployment. Methods: Analysis of data from active duty soldiers returning from Afghanistan or Iraq deployments in fiscal years 2008-2011 who completed Department of Defense health questionnaires after deployment (n = 267,100). Each questionnaire included self-reported alcohol consumption and items yielding AUDIT-C screening scores. Military Health System data were used to identify diagnoses of pain-related conditions. Results: About 70% of soldiers had none of the selected pain diagnoses either pre- or post-deployment. 10% had incident pain diagnoses (only post-deployment), 7% had persistent pain diagnoses (both pre- and post-deployment), and 13% had remitted pain diagnoses (only pre-deployment). On the AUDIT-C, 39% screened positive for at-risk drinking and 6% were likely to have severe alcohol problems. Half of the respondents reported any binge drinking; 20% at least monthly binge drinking. Logistic regression analyses found reduced odds of risky alcohol use post-deployment in association with incident and persistent pain diagnoses, compared to no pain diagnoses pre- or post-deployment. Conclusions: Pain diagnoses, binge drinking, and risky alcohol use were prevalent among this sample of Army soldiers. An inverse relationship was found between pain diagnosis (incident, persistent) and risky alcohol use post-deployment. Attention should continue to be paid to risky alcohol use in this population, yet these exploratory findings do not suggest that soldiers with the pain diagnoses used in this study are at greater risk. Combat exposure, traumatic brain injury, and psychological health were more important predictors, and should continue to warrant enhanced alcohol screening.


Olfactory ensheathing cell transplantation inhibits P2X4 receptor overexpression in spinal cord injury rats with neuropathic pain.
Cell-based therapy is a promising strategy to alleviate neuropathic pain caused by spinal cord injury (SCI). We transplanted olfactory ensheathing cells (OECs) into SCI rats with neuropathic pain and quantitatively detected the sensory nerve function. The expression levels of P2X4 receptor (P2X4R), 200kD neurofilament heavy polypeptide (NF200), and glial fiber acidic protein (GFAP) were measured by immunofluorescence and Western blot analyses. Results showed that NF200 expression significantly increased, GFAP expression decreased, and sensory nerve function improved. In addition, OEC transplantation inhibited the overexpression of P2X4R, which plays an important role in neuropathic pain. Thus, OEC is a candidate target for the treatment of sensory functional loss and P2X4R-mediated neuropathic pain caused by SCI.


[Botulinum toxin A and musculoskeletal pain].
Relaxant muscle properties and pain relieve effectiveness in neurological spasmodic disorders of botulinum toxin A (BTXA) suggested its relevance to relieve musculoskeletal pain. The aim of this article was to collect literature data and to assess the different analgesia indications of BTXA proposed in the treatment of musculoskeletal pains. The international literature was carried out with the Medline data bank using keywords toxin and pain. Only clinical trials have been analysed. Three hundred and seventeen articles were collected and 12 clinical trials were retained. They are focused on 4 chronic diseases, neck pain, tennis elbow, Piriformis syndrome and low back pain. Results of the 6 chronic neck pain studies are contradictory and emphasize the difficulty to display a satisfactory analgesia effect of BTXA in this indication. Results of the studies concerning other indications (tennis elbow, Piriformis syndrome and low back pain) seem to be more effective and clinically pertinent. Analgesia BTXA effect seems to be conditioned by the presence of an objective muscular spasm or stringy disease inducing musculoskeletal pain. The first data concerning use of BTXA to treat musculoskeletal pains are few and are worth specifying by other studies.


Diagnostic success of bronchoscopic biopsy in immunocompromised patients with acute pulmonary disease: predictive value of disease distribution as shown on CT.
The purpose of the study was to determine if the distribution of pulmonary opacities on CT scans could be used to predict the outcome of bronchoscopic biopsy procedures in immunocompromised non-AIDS patients with acute pulmonary complications. Thirty-three consecutive immunocompromised patients without AIDS who had acute pulmonary complications and who had had CT, bronchoscopic biopsy procedures, and proved diagnoses were included in the study. The distribution and dominant pattern of pulmonary opacities on CT were assessed independently by two observers. The pathologic diagnoses were invasive aspergillosis (eight), Candida pneumonia (six), bronchiolitis obliterans with or without organizing pneumonia (six), drug-induced lung disease (four), Pneumocystis carinii pneumonia (four), cytomegalovirus pneumonia (three), pulmonary hemorrhage (one), and recurrent lymphoma (one). The results of bronchoscopic techniques established a specific diagnosis in 17 patients (52%). In the remaining 16 patients, results of bronchoscopic biopsy could not be used to establish a specific diagnosis; open lung biopsy (15 patients) or transthoracic needle biopsy (one patient) were required for diagnosis. The results of bronchoscopic procedures were diagnostic more often in patients in whom pulmonary opacities involved the central third of the lung than in patients in whom the central third was spared (70% vs 23%, p = .02). Results were diagnostic more often in cases in which the causes of acute pulmonary complications were infectious than in cases in which the causes were noninfectious (71% vs 17%, p < .005). We conclude that the presence or absence of central disease as shown by CT can be used to suggest whether results of bronchoscopic procedures in immunocompromised non-AIDS patients will be diagnostic.


Churg-strauss syndrome in an 8-year-old girl.
Churg-Strauss Syndrome (CSS) is a small vessel granulomatous vasculitis that characteristically affects the middle age group and is extremely rare in children. We describe an 8-year-old girl with a prolonged history of cough and eosinophilia that initially was labeled as pulmonary tuberculosis, but after complementary assays, associated with skin biopsy, eosinophilic fibrinoid vasculitis, CSS was eventually diagnosed. In this case, due to her young age and more prevalence of infectious lung diseases in our area, there was a few months delay for correct diagnosis and treatment. After meeting the CSS criteria the appropriate treatment was started and her condition improved.


Effect of Surgical Approach on Pulmonary Function in Adolescent Idiopathic Scoliosis Patients: A Systemic Review and Meta-analysis.
Systemic review and meta-analysis. To analyze the effect of spinal fusion and instrumentation for adolescent idiopathic scoliosis (AIS) on absolute pulmonary function test (PFTs). Pulmonary function is correlated with severity of deformity in AIS patients and studies that have analyzed the effect of spinal fusion and instrumentation on PFTs for AIS have reported inconsistent results. There is a need to analyze the effect of spinal fusion on PFTs with stratification by surgical approach. Our analysis included 22 studies. Cohen's d effect sizes were calculated for absolute PFT outcome measures with 95% confidence intervals (CI). Meta-analyses were performed at each postoperative time frame for six homogeneous surgical approaches: (i) combined anterior release and posterior fusion with instrumentation; (ii) combined video assisted anterior release and posterior fusion with instrumentation without thoracoplasty; (iii) posterior fusion with instrumentation without thoracoplasty; (iv) anterior fusion with instrumentation and without thoracoplasty; (v) video assisted anterior fusion with instrumentation without thoracoplasty; and (vi) any scoliosis surgery with additional thoracoplasty. Anterior spinal fusion with instrumentation, any scoliosis surgery with concomitant thoracoplasty, or video-assisted anterior fusion with instrumentation for AIS had similar absolute PFTs at their 2 year postoperative follow up compared with their preoperative PFTs (effect sizes ranging from -0.2-0.2 with all CI crossing "0"). Posterior spinal fusion with instrumentation (with or without an anterior release) demonstrated small to moderate increases in PFTs 2 years postoperatively (effect sizes ranging from 0.35-0.65 with all CI not crossing "0"). Anterior fusion with instrumentation, regardless of the approach, and any scoliosis surgery with concomitant thoracoplasty do not lead to significant change in pulmonary functions 2 year after surgery. Posterior spinal fusion with instrumentation (with or without an anterior release) resulted in small to moderate increases in PFTs. N/A.


Megakaryopoiesis in chronic myeloproliferative disorders: immunohistochemical evaluation of endoreduplicative activity by PCNA-staining reaction.
A morphometric analysis has been performed on bone marrow trephine biopsies following sequential double-immunostaining with monoclonal antibodies PC10 (anti-proliferating cell nuclear antigen--PCNA) and Y2/51-CD61 (anti-platelet glycoprotein IIIa) to evaluate endoreduplicative activity of megakaryopoiesis. In addition to a control group, patients included different subtypes of chronic myeloproliferative disorders (CMPDs) like chronic myeloid leukaemia (CML), polycythaemia vera (P. vera), primary thrombocythaemia (PTH) and finally primary (idiopathic) osteomyelofibrosis (OMF). In comparison with the normal bone marrow and also with P. vera and PTH a significant increase in PCNA-labelling (late G1 and S phases) of megakaryocytes was recognizable in OMF, contrasting with a striking reduction of this marker in CML. Particularly in advanced stages of OMF, secondary folate deficiency leading to a megaloblastoid appearance of erythroid precursors is a frequent finding. In pernicious anaemia previous cytokinetic studies have demonstrated an arrest in the S phase (DNA synthesis) of the cell cycle due to vitamin B12/folate (haematinic) deficiency. A similar pathomechanism may also be effective in OMF. Consequently, a block in the S phase of the cell cycle is assumed which is in keeping with the increased numbers of PC10-positive megakaryocytes. Significant correlations were calculable between megakaryocyte sizes and PCNA-staining capacity in the normal bone marrow and CMPDs. According to morphometry small-sized (hypoploid) megakaryocytes showed a prevalence of PCNA labelling. This finding is confirmative with a hypothesis on the dynamics of endoreduplicative activity of megakaryocytes, i.e. the prolongation of G1/G2 phases in larger (polyploid) elements. On the other hand, some of the giant polyploid megakaryocytes may cease endoreduplication and enter into G0 phase, which could partially explain the predominance of PCNA-negative large-sized cells of this lineage.


The neurophysin-vasopressin-like system in migratory locust embryos. Immunohistological and radioimmunological studies.
Using immunohistology and radioimmunoassay (RIA), we detected an early synthesis of the neurosecretory product related to vasopressin-neurophysin in the central nervous system of locust embryos. Both techniques gave similar results. By means of immunohistology vasopressin (VP)-like and neurophysin (NP)-like substances can be simultaneously detected as early as stage 10, i.e. 3 days before hatching. Immunofluorescent reactions are visible not only at the level of 2 suboesophageal pericarya but also in fibers and terminal arborizations running in the ventral nerve cord. These results are confirmed by RIAS at stage 10. The VP-like substance could be dosed in the same structures of the central nervous system as where it is normally found in adult locusts. The amounts in the embryos are fairly comparable to those in the adult given the different sizes of their respective nervous system. However, RIAS detected the VP-like neuropeptide in the brain as early as stage 9, i.e. 1 day earlier than with the immunohistological technique.


Structures of three new oleanene glucuronides isolated from Lathyrus palustris var. pilosus and hepatoprotective activity.
Three new saponins, named palustrosides I, II and III, together with azukisaponins II, V and soyasapogenol B monoglucuronide, were isolated from the aerial parts of Lathylus palustris L. var. pilosus Ledeb. The structures of palustrosides I, II and III were identified as 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucuronopyranosides of soyasapogenol E, abrisapogenol E, and bredemolic acid 28-O-beta-D-glucopyranoside, respectively, by spectroscopic and chemical methods. As part of our studies on hepatoprotective drugs, we also examined the hepatoprotective effects of these saponins towards immunologically induced liver injury in primary cultured rat hepatocytes. The activity of the disaccharide group was greater than that of the trisaccharide group. This information regarding the structure-activity relationships substantiated previously obtained data. Structure-hepatoprotective relationships for the sapogenol moiety suggested that the hydroxyl group at C-30 reduces the hepatoprotective effect. On the other hand, the carbonyl group at C-22 may be equivalent to a hydroxyl group at C-22 in terms of hepatoprotective action. Oleanolic acid-type saponins also exhibited hepatoprotective action.


Reading the viral signature by Toll-like receptors and other pattern recognition receptors.
Successful host defense against viral infections relies on early production of type I interferon (IFN) and subsequent activation of a cellular cytotoxic response. The acute IFN and inflammatory response against virus infections is mediated by cellular pattern-recognition receptors (PRRs) that recognize specific molecular structures on viral particles or products of viral replication. Toll-like receptors (TLRs) constitute a class of membrane-bound PRRs capable of detecting microbial infections. While TLR2 and TLR4, which were first identified to recognize Gram-positive and Gram-negative bacteria, respectively, sense specific viral proteins on the cell surface, TLRs 3, 7, 8, and 9 serve as receptors for viral nucleic acids in endosomic compartments. In addition to TLRs, cells express cytoplasmic PRRs such as the RNA helicase retinoic acid inducible gene I and the kinase double-stranded RNA-activated protein kinase R, both of which sense dsRNA, a characteristic signature of viral replication, and initiate a protective cellular response. Here we review the recent progress in our understanding of PRRs and viral infections and discuss the molecular and cellular responses evoked by virus-activated PRRs. Finally, we look into what is currently known about the role of PRRs in viral infections in vivo.


15 years of ATTEMPTS: a macromolecular drug delivery system based on the CPP-mediated intracellular drug delivery and antibody targeting.
Traditionally, any drug intended for combating the tumor would distribute profoundly to other organs and tissues as lack of targeting specificity, thus resulting in limited therapeutic effects toward the tumor but severe drug-induced toxic side effects. To prevail over this obstacle of drug-induced systemic toxicity, a novel approach termed "ATTEMPTS" (antibody targeted triggered electrically modified prodrug type strategy) was designed, which directly introduces both of the targeting and prodrug features onto the protein drugs. The ATTEMPTS system is composed of the antibody targeting component consisting of antibodies linked with heparin, and the cell penetrating peptide (CPP) modified drug component. The two components mentioned above self-assembled into a tight complex via the charge to charge interaction between the anionic heparin and cationic CPP. Once accumulated at the targeting site, the CPP modified drug is released from the blockage by a second triggering agent, while remaining inactive in the circulation during tumor targeting thus aborting its effect on normal tissues. We utilized the heparin-induced inhibition on the cell-penetrating activity of CPP to create the prodrug feature, and subsequently the protamine-induced reversal of heparin inhibition to resume cell transduction of the protein drug via the CPP function. Our approach is the first known system to overcome this selectivity issue, enabling CPP-mediated cellular drug delivery to be practically applicable clinically. In this review, we thoroughly discussed the historical and novel progress of the "ATTEMPTS" system.


Prehospital stroke care: telemedicine, thrombolysis and neuroprotection.
Over the last 15 years, new approaches regarding neuroprotective and thrombolytic strategies in stroke management have been evaluated in the prehospital setting. These efforts have provided exciting new potentials of hyperacute stroke care. Trials have shown that the use of specialized stroke ambulances increases the proportion of patients receiving intravenous thrombolysis and shortens alarm-to-treatment time by approximately half an hour compared to standard care. Intravenous thrombolysis within the ultra-early time window of the 'golden hour' has become a realistic scenario. However, direct effects of prehospital stroke care on functional outcome have yet to be shown and other approaches such as neuroprotective treatments could not demonstrate clinical benefit so far. There is a clear need for systematic research in the prehospital field to test the clinical effectiveness and cost-effectiveness of new therapeutic strategies. It will be necessary to test various components of prehospital stroke care alone and in combination.


Sorption of iodine in soils: insight from selective sequential extractions and X-ray absorption spectroscopy.
The environmental fate of iodine is of general geochemical interest as well as of substantial concern in the context of nuclear waste repositories and reprocessing plants. Soils, and in particular soil organic matter (SOM), are known to play a major role in retaining and storing iodine. Therefore, we investigated iodide and iodate sorption by four different reference soils for contact times up to 30 days. Selective sequential extractions and X-ray absorption spectroscopy (XAS) were used to characterize binding behavior to different soil components, and the oxidation state and local structure of iodine. For iodide, sorption was fast with 73 to 96% being sorbed within the first 24 h, whereas iodate sorption increased from 11-41% to 62-85% after 30 days. The organic fraction contained most of the adsorbed iodide and iodate. XAS revealed a rapid change of iodide into organically bound iodine when exposed to soil, while iodate did not change its speciation. Migration behavior of both iodine species has to be considered as iodide appears to be the less mobile species due to fast binding to SOM, but with the potential risk of mobilization when oxidized to iodate.


Fruit wastes fermentation for phenolic antioxidants production and their application in manufacture of edible coatings and films.
Agro-industrial by-products are important sources of potent bioactive phenolic compounds. These compounds are of extreme relevance for food and pharmacological industries due to their great variety of biological activities. Fermentation represents an environmentally clean technology for production and extraction of these bioactive compounds, providing high quality and high activity extracts, which can be incorporated in foods using coatings/films wax-based in order to avoid alterations in their quality. In this document is presented an overview about importance and benefits of solid-state fermentation, pointing out this bioprocess as an alternative technology for use agro-industrial by-products as substrates to produce valuable secondary metabolites and their applications as food quality conservatives.


Prognostic value of myocardial perfusion imaging performed pre-renal transplantation: post-transplantation follow-up and outcomes.
Noninvasive stress testing is commonly performed as part of pre-renal transplantation (RT) evaluation. We evaluated the prognostic value of myocardial perfusion imaging (MPI)-myocardial perfusion, left ventricular ejection fraction (LVEF) and heart rate response (HRR)-post-RT. Consecutive RT recipients were identified at our institution. MPI was considered abnormal when there was a perfusion defect or reduced ejection fraction. HRR to vasodilator stress was calculated as percentage change from baseline. The primary outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI) and coronary revascularization (CR) post-RT; all-cause mortality was the secondary endpoint. Among 1189 RT recipients, 819 (69%) underwent MPI. Of those, 182 (22%) had abnormal MPI, and 31 (4%) underwent CR pre-RT. During a median follow-up of 56 months post-RT, the annual CV event and mortality rates for patients who had no MPI, normal MPI and abnormal MPI were 1.5%, 3.1% and 4.3% (p < 0.001), and 1.8%, 2.6% and 3.6% (p = 0.016), respectively. After multivariate adjustment, compared to patients without MPI, the hazard ratios (HRs) for CV events for normal and abnormal MPI were 1.47 ([0.93-2.33], p = 0.1) and 1.78 ([1.03-3.06], p = 0.04). Blunted HRR was an independent predictor of CV events (HR = 1.73 [1.04-2.86], p = 0.034) and all-cause death (HR = 2.26 [1.28-3.98], p = 0.005) after adjusting for abnormal MPI. Patients with abnormal MPI who underwent CR pre-RT had annual mortality rates similar to those with no or normal MPI (1.9% vs. 1.7-2.6%, p = 0.2), while those who did not undergo CR had higher annual mortality (4% vs. 1.7-2.6%, p = 0.003). One in five RT recipients who underwent screening MPI had an abnormal study, an independent predictor of CV events. A blunted HRR to vasodilator stress was associated with increased risk of CV events and death, even after adjusting for abnormal MPI. Patients with abnormal MPI who underwent CR were at low risk of mortality following RT. MPI is a useful tool to aid in risk stratification pre-RT.


Wood cellulose preparation methods and mass spectrometric analyses of delta13C, delta18O, and nonexchangeable delta2H values in cellulose, sugar, and starch: an interlaboratory comparison.
Interlaboratory comparisons involving nine European stable isotope laboratories have shown that the routine methods of cellulose preparation resulted in data that generally agreed within the precision of the isotope ratio mass spectrometry (IRMS) method used: +/-0.2 per thousand for carbon and +/-0.3 per thousand for oxygen. For carbon, the results suggest that holocellulose is enriched up to 0.39 per thousand in 13C relative to the purified alpha-cellulose. The comparisons of IRMS measurements of carbon on cellulose, sugars, and starches showed low deviations from -0.23 to +0.23 per thousand between laboratories. For oxygen, IRMS measurements varied between means from -0.39 to 0.58 per thousand, -0.89 to 0.42 per thousand, and -1.30 to 1.16 per thousand for celluloses, sugars, and starches, respectively. This can be explained by different effects arising from the use of low- or high-temperature pyrolysis and by the variation between laboratories in the procedures used for drying and storage of samples. The results of analyses of nonexchangeable hydrogen are very similar in means with standard deviations between individual methods from +/-2.7 to +/-4.9 per thousand. The use of a one-point calibration (IAEA-CH7) gave significant positive offsets in delta2H values up to 6 per thousand. Detailed analysis of the results allows us to make the following recommendations in order to increase quality and compatibility of the common data bank: (1) removal of a pretreatment with organic solvents, (2) a purification step with 17% sodium hydroxide solution during cellulose preparation procedure, (3) measurements of oxygen isotopes under an argon hood, (4) use of calibration standard materials, which are of similar nature to that of the measured samples, and (5) using a two-point calibration method for reliable result calculation.


ABH antigenicity of in situ carcinoma of the urinary bladder during intracavity treatment with doxorubicin hydrochloride.
Ten patients with carcinoma in situ of the urinary bladder were treated topically with doxorubicin hydrochloride. Blood group antigens were evaluated by the specific red cell adherence tests. Carcinoma in situ was associated with the loss of antigenicity, the reappearance of which could be demonstrated in patients with tumour remission. This occurred in spite of a persistent nuclear atypia.


Investigating the root plasticity response of Centaurea jacea to soil water availability changes from isotopic analysis.
-Root water uptake is a key ecohydrological process for which a physically-based understanding has been developed in the past decades. However, due to methodological constraints, knowledge gaps remain about the plastic response of whole plant root systems to a rapidly changing environment. -We designed a laboratory system for non-destructive monitoring of stable isotopic composition in plant transpiration of an herbaceous species (Centaurea jacea) and of soil water across depths, taking advantage of newly developed in-situ methods. Daily root water uptake profiles were obtained using a statistical Bayesian multi-source mixing model. -Fast shifts in the isotopic composition of both soil and transpiration water could be observed with the setup and translated into dynamic and pronounced shifts of the root water uptake profile, even in well-watered conditions. -The incorporation of plant physiological and soil physical information into statistical modelling improved the model output. A simple exercise of water balance closure underlined the non-unique relationship between root water uptake profile on the one hand, and water content and root distribution profiles on the other, illustrating the continuous adaption of the plant water uptake as a function of its root hydraulic architecture and soil water availability during the experiment.


Dual Effect of (LK)nL Peptides on the Onset of Insulin Amyloid Fiber Formation at Hydrophobic Surfaces.
Soluble proteins are constantly in contact with material or cellular surfaces, which can trigger their aggregation and therefore have a serious impact on the development of stable therapeutic proteins. In contact with hydrophobic material surfaces, human insulin aggregates readily into amyloid fibers. The kinetics of this aggregation can be accelerated by small peptides, forming stable beta-sheets on hydrophobic surfaces. Using a series of (LK)nL peptides with varying length, we show that these peptides, at low, substoichiometric concentrations, have a positive, cooperative effect on insulin aggregation. This effect is based on a cooperative adsorption of (LK)nL peptides at hydrophobic surfaces, where they form complexes that help the formation of aggregation nuclei. At higher concentrations, they interfere with the formation of an aggregative nucleus. These effects are strictly dependent on the their adsorption on hydrophobic material surfaces and highlight the importance of the impact of materials on protein stability. (LK)nL peptides prove to be valuable tools to investigate the mechanism of HI aggregation nuclei formation on hydrophobic surfaces.


[Comparison of sensitivity of mental load assessment indexes].
Objective. To compare the sensitivities of indexes used in the assessment of mental load. Method. Twenty five indexes belonging to primary task performance, additional task performance, subjective rate and psychophysiological measure were recorded during performance of 11 different difficult tasks. Result. It showed that tracking error (ER), reaction time (RT), correct rate (CR), category scale (CS), multistage evaluation scale (MES), multi-dimensional scale (MDS), latency of P3 (LAT), inter beat interval (IBI), inter respiration interval (IRI) and blink rate (BR) were significantly different among the various tasks. CS, MES and MDS were more sensitive to the total load; ER, LAT, IBI and IRI were more sensitive to the load of primary task, while RT and CR to that of additional task and BR to the visual load. Conclusion. It demonstrated that the sensitivities of the various indexes are different and the information are limited. Multi-indexes may be preferred for mental load assessment.


Mandarin Electrolaryngeal Speech Recognition Based on WaveNet-CTC.
Purpose The application of Chinese Mandarin electrolaryngeal (EL) speech for laryngectomees has been limited by its drawbacks such as single fundamental frequency, mechanical sound, and large radiation noise. To improve the intelligibility of Chinese Mandarin EL speech, a new perspective using the automatic speech recognition (ASR) system was proposed, which can convert EL speech into healthy speech, if combined with text-to-speech. Method An ASR system was designed to recognize EL speech based on a deep learning model WaveNet and the connectionist temporal classification (WaveNet-CTC). This system mainly consists of 3 parts: the acoustic model, the language model, and the decoding model. The acoustic features are extracted during speech preprocessing, and 3,230 utterances of EL speech mixed with 10,000 utterances of healthy speech are used to train the ASR system. Comparative experiment was designed to evaluate the performance of the proposed method. Results The results show that the proposed ASR system has higher stability and generalizability compared with the traditional methods, manifesting superiority in terms of Chinese characters, Chinese words, short sentences, and long sentences. Phoneme confusion occurs more easily in the stop and affricate of EL speech than the healthy speech. However, the highest accuracy of the ASR could reach 83.24% when 3,230 utterances of EL speech were used to train the ASR system. Conclusions This study indicates that EL speech could be recognized effectively by the ASR based on WaveNet-CTC. This proposed method has a higher generalization performance and better stability than the traditional methods. A higher accuracy of the ASR system based on WaveNet-CTC can be obtained, which means that EL speech can be converted into healthy speech. Supplemental Material https://doi.org/10.23641/asha.8250830.


An outbreak of Japanese encephalitis in a non-endemic region of north-east India.
Background There are few comprehensive reports of epidemic Japanese encephalitis in a previously unaffected region. We report our experience of a first-ever outbreak of it in Sonitpur District, Assam, India, with 45 laboratorycon confirmed cases at a single hospital. Method Between 2 July and 11 August 2008, patients meeting the WHO definition of acute encephalitis syndrome were assessed in a single hospital and had tests including blood and cerebrospinal fluid for Japanese encephalitis antibody titres. Results Ninety-six cases meeting the definition of acute encephalitis syndrome were identified with 45 cases of Japanese encephalitis confirmed by cerebrospinal fluid or blood results. For Japanese encephalitis positive patients, mean age was 36 (range 4-80). Of the 45, 11 (24%) died and a further 21 (47%) had significant residual deficits. Focal neurological signs (40%) and seizures (25%) were common. Conclusion An effective Japanese encephalitis vaccine is the key intervention for limiting the population impact of this disease. Identification of these cases led to a district-wide mass vaccination campaign.


Characterization of mesenchymal stem cells in sheep naturally infected with scrapie.
Mesenchymal stem cells (MSCs) can be infected with prions and have been proposed as in vitro cell-based models for prion replication. In addition, autologous MSCs are of interest for cell therapy in neurodegenerative diseases. To the best of our knowledge, the effect of prion diseases on the characteristics of these cells has never been investigated. Here, we analysed the properties of MSCs obtained from bone marrow (BM-MSCs) and peripheral blood (PB-MSCs) of sheep naturally infected with scrapie — a large mammal model for the study of prion diseases. After three passages of expansion, MSCs derived from scrapie animals displayed similar adipogenic, chondrogenic and osteogenic differentiation ability as cells from healthy controls, although a subtle decrease in the proliferation potential was observed. Exceptionally, mesenchymal markers such as CD29 were significantly upregulated at the transcript level compared with controls. Scrapie MSCs were able to transdifferentiate into neuron-like cells, but displayed lower levels of neurogenic markers at basal conditions, which could limit this potential .The expression levels of cellular prion protein (PrPC) were highly variable between cultures, and no significant differences were observed between control and scrapie-derived MSCs. However, during neurogenic differentiation the expression of PrPC was upregulated in MSCs. This characteristic could be useful for developing in vitro models for prion replication. Despite the infectivity reported for MSCs obtained from scrapie-infected mice and Creutzfeldt–Jakob disease patients, protein misfolding cyclic amplification did not detect PrPSc in BM- or PB-MSCs from scrapie-infected sheep, which limits their use for in vivo diagnosis for scrapie.


Computational design of metal-free catalysts for catalytic hydrogenation of imines.
Using MeN=CMe(2) as an imine model, computational chemistry has been applied to design metal-free hydrogenation catalysts. The implementation includes designing proper electronic structures to split H(2) and building appropriate chemical scaffolds to prevent possible side reactions which may deactivate the catalysts. Interestingly, the designed catalysts bear resemblances to the well-known metal-ligand bifunctional hydrogenation catalysts in terms of both the activation principle and the hydrogenation mechanisms. The hydrogenations catalyzed by the designed catalysts proceed via two major steps, hydrogen activation and hydrogen transfer. The predicted energetics for completing the catalytic cycles indicate that these reactions have feasible kinetics and thermodynamics for experimental realizations under ambient conditions. We also showed how to improve the catalysis by using the "cooperative effect" and the non-bonding interactions. The reported catalysts can be the targets for experimental synthesis. The strategy can be borrowed to design similar catalysts.


Identification of differential expressed transcripts in cervical cancer of Mexican patients.
The aim of this study was to identify the gene expression profile in biopsies of patients with cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3, and microinvasive cancer by suppression subtractive hybridization and Southern blotting. After analyzing 1,800 cDNA clones, we found 198 upregulated genes, 166 downregulated, and no significant change of gene expression in 86 clones (p = 0.005). These results were validated by Northern blot analysis (p = 0.0001) in the identification of 28 overexpressed and 7 downregulated transcripts. We observed a set of genes related to the Notch signaling pathway that may be involved in the transformation of cervical cells and in the development to malignancy. The differentially expressed genes may provide useful information about the molecular mechanisms involved in human cervical carcinoma and as diagnostic markers.


Expression of interleukin-18 and its monokine-directed function in rheumatoid arthritis.
To investigate the expression of and monokine induction by interleukin 18 (IL-18; also called interferon-gamma inducing factor, IGIF), in peripheral blood mononuclear cells (PBMC) and cultured synoviocytes from rheumatoid arthritis (RA) patients. We carried out IL-18 Western blotting and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) of cytokines in PBMC [IL-18, IL-1beta and tumour necrosis factor alpha (TNF-alpha)] and long-term cultured fibroblast-like synoviocytes (FLS) [IL-18, IL-1beta, TNF-alpha, IL-6, interferon gamma (INF-gamma) and [granulocyte-macrophage colony stimulating factor (GM-CSF)] from RA patients and controls. FLS were isolated from RA synovial membranes (FLS(SM)) and RA synovial fluids (FLS(SF)), osteoarthritis (OA) FLS(SM) and FLS(SF) from spondyloarthropathy patients. FLS were characterized by fluorescence-activated cell sorting of the FLS. PBMC and FLS from RA patients and control subjects were stimulated with recombinant human IL-18 and IL-1beta (rHuIL-18/rHuIL-1beta), and TNF-alpha, IL-1beta and MMP-1 were measured by ELISA in supernatants. Constitutive expression of IL-18 mRNA was significantly reduced whereas that of TNF-alpha was enhanced in RA PBMC. Persistent low expression of IL-18, TNF-alpha, GM-CSF and IL-1beta was observed in RA and OA FLS(SM) as well as spondyloarthropathy FLS(SF). In contrast, high constitutive expression of IL-18 in FLS (CD90/Thy-1- and CD54-positive, CD14- and CD86-negative), accompanied by persistent high levels of TNF-alpha, GM-CSF and IL-1beta expression, was restricted to synovial fluid-derived FLS obtained from RA patients. IFN-gamma was not detectable in any culture, but IL-6 mRNA was equally expressed in all FLS cultures. rHuIL-18 was effective in stimulating TNF-alpha and IL-1beta secretion in PBMC from healthy controls, but failed to stimulate TNF-alpha and IL-1beta secretion from PBMC in 11 of 12 RA patients, and all FLS cultures. rHu-IL-1beta, but not rHu-IL-18, induced interstitial collagenase (MMP-1) in FLS. Persistent high production of proinflammatory cytokines in RA-FLS(SF) may be relevant for chronic progression in RA synovitis. Levels of TNF-alpha and IL-1beta expression are increased in RA-FLS(SF), but are independent of IL-18. The pathological function of enhanced IL-18 expression in RA-FLS(SF) remains to be further elucidated.


Anomalous odd-even effects in columnar and smectic phases of discotic tetraphenylenes.
Rather uncommon but pronounced odd-even effects in the clearing temperatures of liquid crystals are found for three new homologous series of discotic tetraphenylenes [figure: see text]. Detailed similarities to the well-known odd-even effects in calmitic mesogens point towards a more general understanding of odd-even effects in liquid crystals.The phase transition temperatures in many homologous series of liquid crystals show odd-even effects similar to the well-known odd-even effects in non-mesogenic organic compounds like carboxylic acids. For discotic liquid crystals only a few series with a sufficient number of consecutive homologues are available and only a small part of these series show odd-even effects at all. We now synthesized and investigated three series of discotic tetraphenylenes each ranging from the n=7 to the n=16 homologues. For these compounds an anomalous odd-even effect is found: The ascending and descending transition temperatures with increasing number of methylene groups in the side chains exhibit an inversion of this alternation which is always found between the n=12 and n=14 homologues. An overview of odd-even effects in liquid crystals is presented and we discuss the nature and the origin of odd-even effect in discotic mesogens.


A newly created splice donor site in exon 25 of the MyBP-C gene is responsible for inherited hypertrophic cardiomyopathy with incomplete disease penetrance.
Hypertrophic cardiomyopathy is a myocardial disorder resulting from inherited sarcomeric dysfunction. We report a mutation in the myosin-binding protein-C (MyBP-C) gene, its clinical consequences in a large family, and myocardial tissue findings that may provide insight into the mechanism of disease. History and clinical status (examination, ECG, and echocardiography) were assessed in 49 members of a multigeneration family. Linkage analysis implicated the MyBP-C gene on chromosome 11. Myocardial mRNA, genomic MyBP-C DNA, and the myocardial proteins of patients and healthy relatives were analyzed. A single guanine nucleotide insertion in exon 25 of the MyBP-C gene resulted in the loss of 40 bases in abnormally processed mRNA. A 30-kDa truncation at the C-terminus of the protein was predicted, but a polypeptide of the expected size ( approximately 95 kDa) was not detected by immunoblot testing. The disease phenotype in this family was characterized in detail: only 10 of 27 gene carriers fulfilled diagnostic criteria. Five carriers showed borderline hypertrophic cardiomyopathy, and 12 carriers were asymptomatic, with normal ECG and echocardiograms. The age of onset in symptomatic patients was late (29 to 68 years). In 2 patients, outflow obstruction required surgery. Two family members experienced premature sudden cardiac death, but survival at 50 years was 95%. Penetrance of this mutation was incomplete and age-dependent. The large number of asymptomatic carriers and the good prognosis support the interpretation of benign disease.


A disulfide-linked naphthalimide dimer for Hg(II) detection in aqueous solution.
A disulfide linked naphthalimide dimer probe was designed for mercury ion (Hg(2+)) recognition in this work. The recognition was based on the strong affinity of mercury for sulfur. The experimental results revealed that the probe exhibited high selectivity and sensitivity toward Hg(2+) in comparison to other metal ions via a turn-on and reversible response to Hg(2+) in neutral buffer solution. More importantly, the probe demonstrated a linear response for Hg(2+) over a concentration range from 0 to 150 μM with a detection limit of 0.38 μM, which is just the limit of the safe concentration for humans. Upon addition of 150 μM Hg(2+), the enhancement of fluorescence reached a maximum (∼7-fold). The performances of the probe indicated that it could meet the selectivity requirements for biomedical and environmental application and also was sensitive enough to detect Hg(2+) in environmental and biological samples.


Comparison of blood gas, electrolyte and metabolite results measured with two different blood gas analyzers and a core laboratory analyzer.
Blood gas analyzers (BGAs) are important in assessing and monitoring critically ill patients. However, the random use of BGAs to measure blood gases, electrolytes and metabolites increases the variability in test results. Therefore, this study aimed to investigate the correlation of blood gas, electrolyte and metabolite results measured with two BGAs and a core laboratory analyzer. A total of 40 arterial blood gas samples were analyzed with two BGAs [(Nova Stat Profile Critical Care Xpress (Nova Biomedical, Waltham, MA, USA) and Siemens Rapidlab 1265 (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA)) and a core laboratory analyzer [Olympus AU 2700 autoanalyzer (Beckman-Coulter, Inc., Fullerton, CA, USA)]. The results of pH, pCO₂, pO₂, SO₂, sodium (Na⁺), potassium (K⁺), calcium (Ca⁺²), chloride (Cl⁻), glucose, and lactate were compared by Passing-Bablok regression analysis and Bland-Altman plots. The present study showed that there was negligible variability of blood gases (pCO₂, pO₂, SO₂), K⁺ and lactate values between the blood gas and core laboratory analyzers. However, the differences in pH were modest, while Na⁺, Cl⁻, Ca²⁺ and glucose showed poor correlation according to the concordance correlation coefficient. BGAs and core laboratory autoanalyzer demonstrated variable performances and not all tests met minimum performance goals. It is important that clinicians and laboratories are aware of the limitations of their assays.


Student experiences in creating and launching a student-led physical therapy pro bono clinic: a qualitative investigation.
The physical therapy profession has called for the provision of pro bono services. Little is known about the impact on students involved in sustainable pro bono leadership. One physical therapy program established a pro bono physical therapy clinic under the direct leadership of a board of students. The purpose of this study was to describe the experiences of the inaugural members of the Chester Community Physical Therapy Clinic Student Board in creating and launching the student-led pro bono physical therapy clinic. A purposive sample of the 18 members participated in semistructured interviews. Content analysis was conducted using a commercially available software program. Trustworthiness was enhanced with credibility, transferability, and confirmability. The emergent categories were: (1) leadership skill development, (2) competency in hands-on clinical and administrative skills, and (3) commitment to both the community and the clinic. Pride emerged as a strong and overarching theme throughout the experience. The student-led pro bono clinic meets several Commission on Accreditation in Physical Therapy Education criteria in a sustainable manner and serves as a means for measuring and meeting program mission and goals. Participation in the program was a meaningful experience and developed ownership, leadership skills, and pride among the students. There are also possibilities for expanding aspects of the program so that all physical therapist students can benefit from pro bono service opportunities.


The clinical significance of endothelial dysfunction.
Endothelial dysfunction is thought to play a pivotal role in the development, progression, and clinical complications of atherosclerosis. Several recent studies have addressed the clinical implications of endothelial dysfunction for cardiovascular events, atherosclerosis, restenosis, and heart failure. Novel findings with respect to endothelial progenitor cells and their alteration by cardiovascular risk factors are characterized and potential therapeutic interventions to improve endothelial and endothelial progenitor cell function are discussed. Over the past 5 years evidence has accumulated from clinical studies for a close association of the degree of endothelial dysfunction and clinical cardiovascular events in patients with cardiovascular risk factors, coronary disease, acute coronary syndrome, or heart failure. Understanding of the mechanisms leading to endothelial dysfunction has improved, including the notion that dysfunctional endothelial nitric oxide synthase, in part due to deficiency of the endothelial nitric oxide synthase cofactor tetrahydrobiopterin, likely plays an important role. Major progress has been made in understanding the role of endothelial progenitor cells, which likely contribute to both ischemia-induced neovascularization and endothelial regeneration after injury. Endothelial progenitor cell function is altered in patients with cardiovascular risk factors. Recent research on endothelial and endothelial progenitor cell dysfunction supports their clinical significance and has led to important insights in the pathophysiology of cardiovascular disease and at the same time provides an important opportunity to develop novel therapeutic approaches. Endothelial function represents a valuable surrogate endpoint to assess the impact of therapeutic interventions.


Nocardia asiatica sp. nov., isolated from patients with nocardiosis in Japan and clinical specimens from Thailand.
Five strains isolated from two patients with nocardiosis in Japan and three clinical samples from Thailand were found to have morphological, biochemical and chemotaxonomic properties consistent with their classification in the genus Nocardia. DNA-DNA hybridization, coupled with sequence analysis of 16S rDNA, indicated that these strains belong to a novel species of the genus Nocardia, named Nocardia asiatica sp. nov. because the isolation sites were in Asian countries; the type strain is IFM 0245T (=NBRC 100129T=JCM 11892T=DSM 44668T).


Azasterols impair Giardia lamblia proliferation and induces encystation.
The effects of sterol biosynthesis inhibitors on growth and fine structure of Giardia lamblia P1 strain cultures were analyzed. Azasterols demonstrated high efficacy in killing cells. The IC(50) values for 22,26-azasterol and 24(R,S),25-epiminolanosterol were 7muM and 170nM, respectively. Morphological analysis showed that azasterols induced changes in G. lamblia ultrastructure. The most significant alterations were: (a) considerable increase of the size of the peripheral vesicles, which are part of the parasite endosomal-lysosomal system; (b) appearance of autophagosomal structures; and (c) induction of differentiation, followed by an abnormal enlargement of encystation secretory vesicles. We propose that azasterols are effective chemotherapeutic drugs against Giardia lamblia in vitro and may have another target in cells besides sterol biosynthesis.


A three-level hearing screening program for school children.
This study reports the results of a hearing screening program that was conducted in a number of schools in Alexandria region in the school year 1997-1998. Schools were classified according to location into urban and suburban schools. Screening was done in three separate levels. In the first level, screening was done by health visitors in classrooms. To pass the screening in this level, the student had to indicate hearing of 30, 30, 25 & 25 dB tones at 1000, 2000, 4000 & 8000 Hz, respectively. A total of 6180 students were screened in this level, and only 10% of them (614 students) failed. The failing students were referred for the second level of screening in Sporting Hospital for School Students. The screening was done by trained health visitors in sound treated rooms, and to pass this level the child had to indicate hearing of 25 dB tones at 250, 500, 1000, 2000, 4000 & 8000 Hz. From 225 students who attended this level, only 75 students passed. The failing students were assumed to have a hearing problem and were referred for audiologic diagnosis by a consultant audiologist in the third level. The number of students attending the third level were 67 students and all of them had a hearing deficit. In 44 of them occluding wax was the cause of failure and upon its removal they proved to have normal hearing. Twenty three students had hearing loss due to secretory otitis media, chronic suppurative otitis media, or sensory neural hearing loss. The estimated prevalence of hearing loss in school children in this study ranged between 1.17 and 2.59%.


A study on the antagonism of the intestinal inhibitory effects of morphine and clonidine by yohimbine in mice.
In mice, clonidine administered subcutaneously caused a dose-dependent inhibition of the intestinal motility as assayed by the movement of a charcoal meal. This inhibitory effect of clonidine was antagonized dose-dependently by prior subcutaneous or intracisternal administration of yohimbine. However, yohimbine given intracerebroventricularly was ineffective in antagonising the intestinal inhibitory action of clonidine. Clonidine administered centrally, either intracisternally or intracerebroventricularly, caused a dose-dependent inhibition of intestinal motility. Clonidine given by the intracisternal route appeared to be more effective than by the intracerebroventricular route. Centrally administered clonidine was antagonized by prior subcutaneous administration of yohimbine. The antagonism was related to the doses of yohimbine given. Subcutaneously administered morphine caused a dose-dependent inhibition of intestinal motility and this effect was antagonized by prior subcutaneous administration of yohimbine. However, administration of yohimbine centrally, either intracisternally or intracerebroventricularly, did not affect the intestinal inhibitory action of morphine. On the other hand, morphine injected centrally, either intracisternally or intracerebroventricularly, dose-dependently inhibited the motility of the intestine; such inhibitory action was antagonized by prior subcutaneous administration of yohimbine. The present study suggests that clonidine inhibits intestinal motility at both central and peripheral sites through alpha 2-adrenoceptors. Morphine also inhibits intestinal motility by both central and peripheral mechanisms but it appears that yohimbine only modifies the peripheral aspect of morphine's action.