Malformation syndrome associated with small extra chromosome.
We report an infant with a previously apparently unreported lethal malformation syndrome concentrated primarily on the left half of the body, but including midline defects such as meningomyelocele, cleft lip and cleft palate, and imperforate anus. The infant also had a small extra metacentric chromosome in 60% of lymphocytes. It is postulated that the small extra chromosome (whose origin remains unknown) caused the infant's condition, and that its asymmetry is compatible with an uneven distribution of the normal and aneuploid cell lines in the two halves of the body during critical phases of prenatal development.


Signal transduction of reactive oxygen species and mitogen-activated protein kinases in cardiovascular disease.
Reactive oxygen species (ROS), generated by reduction-oxidation (redox) reactions, have been recognized as important chemical mediators that regulate signal transduction. It has been reported that increase in ROS generation may relate to a risk for cardiovascular diseases such as atherosclerosis, angina pectoris, and myocardial infarction. Therefore, understanding the ROS-generating biological processes and ROS-induced intracellular signaling will be informative to gain insights into the pathogenesis of these diseases. In this review, we focus on the sources and reactions of ROS in the cardiovascular system and the role of mitogen-activated protein (MAP) kinase pathway in redox-mediated signal transduction. Clinical implications of ROS and MAP kinase are then described to provide insight into the pathogenesis of various redox-sensitive cardiovascular diseases. The pathways responsible for ROS generation in the cardiovascular system may provide novel therapeutic targets.


[BRONCHOPLASTY FOR LUNG CANCER].
Bronchoplasty for patients with lung cancer is basically designed to achieve radical cure with the preservation of lung function. Functional lung parenchyma can be preserved, and the reimplanted lobes contribute to postoperative quality of life. Pneumonectomy is associated with a higher occurrence of postoperative complications, poor quality of life, and cardiopulmonary dysfunction as compared with lobectomy. In addition, long-term complications (i.e., late pulmonary hypertension, respiratory failure, or so-called postpneumonectomy syndrome) are sometimes seen after pneumonectomy but seldom after lobectomy. Thus pneumonectomy itself is considered a disease. Sleeve lobectomy, or lobectomy with bronchoplasty, which allows the preservation of functional lung parenchyma with the possible advantages of lower mortality and morbidity rates, is a valid alternative to pneumonectomy and has recently been accepted as a standard treatment in noncompromised patients with lung cancer. Atypical bronchoplasties such as double-sleeve and extended-sleeve lobectomy, and sleeve segmentectomy are also performed at present. This article describes the surgical techniques for bronchoplastic procedures and compares the surgical outcomes of sleeve lobectomy with those of pneumonectomy reported in the literature.


Ionization yields in hydrocarbons under electron irradiation.
Ionization yields and W-values in several hydrocarbon gases under electron irradiation have been calculated using Inokuti's solution of the Fowler equation, i.e., incorporating a linear dependence of ionization yield on source electron energy. Collision stopping powers of hydrocarbons were evaluated using the Bethe formula with mean excitation energies determined using the additivity rule with modification based on molecular bond strengths. Contributions to the collision stopping powers from discrete level excitations were estimated by multiplying collision stopping powers by the excitation fractions constructed from atomic calculations. Average energy transfers for ionizing collisions producing subionization electrons were calculated using differential ionization cross sections proposed by Khare and co-workers. The calculated W-values are in good agreement with those recommended by ICRU.


Broad screening and identification of β-agonists in feed and animal body fluid and tissues using ultra-high performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry combined with spectra library search.
Broad screening and identification of β-agonists in feed, serum, urine, muscle and liver samples was achieved in a quick and highly sensitive manner using ultra high performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) combined with a spectra library search. Solid-phase extraction technology was employed for sample purification and enrichment. After extraction and purification, the samples were analyzed using a Q-Orbitrap high-resolution mass spectrometer under full-scan and data-dependent MS/MS mode. The acquired mass spectra were compared with an in-house library (compound library and MS/MS mass spectral library) built with TraceFinder Software which contained the M/Z of the precursor ion, chemical formula, retention time, character fragment ions and the entire MS/MS spectra of 32 β-agonist standards. Screening was achieved by comparing 5 key mass spectral results and positive matches were marked. Using the developed method, the identification results from 10 spiked samples and 238 actual samples indicated that only 2% of acquired mass spectra produced false identities. The method validation results showed that the limit of detection ranged from 0.021-3.854 μg kg(-1)and 0.015-1.198 ng mL(-1) for solid and liquid samples, respectively.


Additional antilipoperoxidant activities of alpha-tocopherol and ascorbic acid on membrane-like systems are potentiated by rutin.
The effects of alpha-tocopherol, ascorbic acid and rutin on peroxidative processes were studied in xanthine-xanthine oxidase system, linoleic acid ufasomes and human erythrocyte membranes. In these three systems, tested compounds scavenge superoxide anion radicals or inhibit lipid peroxidation in a concentration-dependent manner, and it was shown that rutin was the most potent radical scavenger, followed by ascorbic acid and alpha-tocopherol. An important antilipoperoxidant activity was observed when these compounds were tested in combination, demonstrating that a dose-dependent interaction occurs. Water-soluble (rutin and ascorbic acid) as well as lipid-soluble (tocopherol) antioxidants are involved in the protection of polyunsaturated fatty acids constituting the ufasome or erythrocyte ghosts. When these compounds are used in combination, an additive effect is observed with alpha-tocopherol and ascorbic acid or rutin, while a supra-additive effect (synergism) is noted with ascorbic acid and rutin. Results obtained with the triple combination alpha-tocopherol-ascorbic acid-rutin show that an increase in superoxide radical scavenging activities or in lipid peroxidation inhibition is possible after the addition of a third antioxidant, as compared with the protective effects produced by the double combination of these compounds. This interaction takes place not only in homogeneous aqueous solutions, but also in ufasome or erythrocyte ghost preparations. It is suggested that ascorbic acid and rutin interacts with tocopherol at the surface of or the interface with the membrane, and that rutin simultaneously interacts with ascorbic acid.


[Tetanus prophylaxis. Proposed rationalization of procedure in the occupational field].
After a recent increase in cases of tetanus in Italy, the Ministry of Health has proposed vaccination of the entire population, inviting local physicians to cooperate towards this end. The author suggests periodic dosage of tetanus antitoxin antibodies as the most economic and efficient method of identifying workers who are not protected by vaccination.


Inhibitory effect of 2‑mercaptoethane sulfonate on the formation of Escherichia coli biofilms in vitro.
The biofilms (BF) formed by Escherichia coli (E. coli) is an important cause of chronic and recurrent infections due to its capacity to persist on medical surfaces and indwelling devices, demonstrating the importance of inhibiting the formation of E. coli BF and reducing BF infection. Although 2‑mercaptoethane sulfonate (MESNA) exhibits a marked mucolytic effect clinically, the effect of MESNA on the inhibition of E. coli BF formation remains to be elucidated. The present study investigated whether MESNA inhibits the formation of E. coli BF in vitro. The minimum inhibitory concentration of MESNA on E. coli was determined to be 10 mg/ml. Subsequently, the effect of MESNA on BF early adhesion, extracellular polysaccharide (EPS) and extracellular protein were detected. The effect of a subinhibitory concentration of MESNA on BF formation was evaluated, and the inhibitory potency of MESNA against matured BF was assayed. The results revealed that MESNA inhibited early stage adhesion and formation of the E. coli BF, destroyed the mature BF membrane and reduced the EPS and extracellular proteins levels of the BF. In addition, the present study investigated the effects of MESNA on the expression of EPS‑ and adhesion protein‑associated genes using quantitative polymerase chain reaction analysis, which demonstrated that MESNA effectively inhibited the expression of these genes. These results suggested that MESNA possesses anti‑BF formation capability on E. coli in vitro and may be used as a potential reagent for the clinical treatment of E. coli BF‑associated infections.


Surface molecular imprinting onto fluorescein-coated magnetic nanoparticles via reversible addition fragmentation chain transfer polymerization: a facile three-in-one system for recognition and separation of endocrine disrupting chemicals.
In this study, we present a general protocol for the making of surface-imprinted magnetic fluorescence beads via reversible addition-fragmentation chain transfer polymerization. The resulting composites were characterized by X-ray diffraction analysis, transmission electron microscopy, scanning electron microscopy, fluorescence spectroscopy, Fourier transform infrared spectroscopy, and energy dispersive spectroscopy. The as-synthesized beads exhibited homogeneous polymer films (thickness of about 5.7 nm), spherical shape, high fluorescence intensity and magnetic property (Magnetization (Ms)=3.67 emu g(-1)). The hybrids bind the original template 17β-estradiol with an appreciable selectivity over structurally related compounds. In addition, the resulting hybrids performed without obvious deterioration after five repeated cycles. This study therefore demonstrates the potential of molecularly imprinted polymers for the recognition and separation of endocrine disrupting chemicals.


Wheat Fhb1 encodes a chimeric lectin with agglutinin domains and a pore-forming toxin-like domain conferring resistance to Fusarium head blight.
Fusarium head blight (FHB), caused by Fusarium graminearum, is a devastating disease of wheat and barley that leads to reduced yield and mycotoxin contamination of grain, making it unfit for human consumption. FHB is a global problem, with outbreaks in the United States, Canada, Europe, Asia and South America. In the United States alone, total direct and secondary economic losses from 1993 to 2001 owing to FHB were estimated at $7.67 billion. Fhb1 is the most consistently reported quantitative trait locus (QTL) for FHB resistance breeding. Here we report the map-based cloning of Fhb1 from a Chinese wheat cultivar Sumai 3. By mutation analysis, gene silencing and transgenic overexpression, we show that a pore-forming toxin-like (PFT) gene at Fhb1 confers FHB resistance. PFT is predicted to encode a chimeric lectin with two agglutinin domains and an ETX/MTX2 toxin domain. Our discovery identifies a new type of durable plant resistance gene conferring quantitative disease resistance to plants against Fusarium species.


Aflatoxin, proximate composition and mineral profile of stored broiler feed treated with medicinal plant leaves.
In the present investigation, the Morus alba (M. alba), Vitis vinifera (V. vinifera), Ficus religiosa (F. religiosa) and Citrus paradisi (C. paradisi) leaves anti-aflatoxigenic activities were evaluated in Aspergillus flavus (A. flavus) inoculated feed. The broiler feed inoculated with A. flavus was treated with selected medicinal plant leaf powder (5%, 10% and 15% w/w) and stored for the period of six months at 28°C and 16% moisture. The aflatoxins (AFTs) were estimated at the end of each month by Reversed Phase High Performance Liquid Chromatography (RP-HPLC) method along with proximate composition and mineral contents. Plant leaves controlled AFTs efficiently without affecting the feed proximate composition and mineral contents. The M. alba leaves completely inhibition (100%) the AFTs (B1 and B2) in feed at very low concentration (5%). Other plants also showed significant (P<0.05) inhibition of AFTs production without affecting the feed quality over the storage period of six months. Based on promising efficiency of selected medicinal plant leaves, A. flavus produced AFTs could possibly be controlled in stored poultry feed.


High-throughput, non-invasive prenatal testing for fetal Rhesus D genotype to guide antenatal prophylaxis with anti-D immunoglobulin: a cost-effectiveness analysis.
To evaluate the cost-effectiveness of high-throughput, non-invasive prenatal testing (HT-NIPT) for fetal Rhesus D (RhD) genotype to guide antenatal prophylaxis with anti-D immunoglobulin compared with routine antenatal anti-D immunoglobulin prophylaxis (RAADP). Cost-effectiveness decision-analytic modelling. Primary care. A simulated population of 100 000 RhD-negative women not known to be sensitised to the RhD antigen. A decision tree model was used to characterise the antenatal care pathway in England and the long-term consequences of sensitisation events. The diagnostic accuracy of HT-NIPT was derived from a systematic review and bivariate meta-analysis; estimates of other inputs were derived from relevant literature sources and databases. Women in whom the HT-NIPT was positive or inconclusive continued to receive RAADP, whereas women with a negative result received none. Five alternative strategies in which the use of HT-NIPT may affect the existing postpartum care pathway were considered. Costs expressed in 2015GBP and impact on health outcomes expressed in terms of quality-adjusted life-years over a lifetime. The results suggested that HT-NIPT appears cost saving but also less effective than current practice, irrespective of the postpartum strategy evaluated. A postpartum strategy in which inconclusive test results are distinguished from positive results performed best. HT-NIPT is only cost-effective when the overall test cost is £26.60 or less. HT-NIPT would reduce unnecessary treatment with routine anti-D immunoglobulin and is cost saving when compared with current practice. The extent of any savings and cost-effectiveness is sensitive to the overall test cost. HT-NIPT is cost saving compared with providing anti-D to all RhD-negative pregnant women.


Dose-response effects of inulin and oligofructose on intestinal bifidogenesis effects.
Recent studies have identified several beneficial attributes of inulin (I) and oligofructose (OF) in human health. However, most of the studies pertaining to the physiologic role of these compounds have been conducted at higher concentrations (8-40 g/d) as a source of dietary fiber. There is growing interest in using I and OF as a substrate for the selective growth of beneficial gastrointestinal bacteria such as the bifidobacteria. In vitro fermentation studies using fecal inoculums have shown that I and OF are utilized rapidly and completely by intestinal microflora and that the degree of polymerization of the substrate influenced its rate of disappearance. In these and other studies, I and OF were shown to be efficient substrates for the growth of most strains of bifidobacteria compared with glucose. In vivo studies have also shown that when human volunteers ingested I or OF, the number of fecal bifidobacteria increased. However, when results from the reported studies are combined and analyzed, a dose-response relationship in terms of log increases in the count of bifidobacteria cannot be demonstrated. Initial numbers of bifidobacteria in the feces, independent of the dose of the fructo-oligosaccharides, seem to influence the results. Future investigations should consider this relationship carefully.


[Disinfection of wood in mushroom growing cellars with Mycetox].
Since the use od phenolic disinfectants for impregnating and disinfecting of wood in mushroom--growing cellars was banned in Poland for ecologic and hygienic reasons, the new product, namely Mycetox, containing quaternary ammonium compound and boric acid has been registered for this purpose. Mycetox belongs to new generation products and is non toxic for man and the environment. It is first Polish product developed for the general disinfection as well as for impregnating purposes in mushroom farms. The efficacy of Mycetox in mushroom-growing cellars has been evaluated basing on its fungicidal properties in the different substrates used for the cultivation of mushrooms. Also its influence on mushroom spawn growth, crop yield, and the penetration of spawn into wooden cages impregnated with Mycetox as well as its influence on blanching of mushrooms has been investigated.


Stem cell treatment for Parkinson's disease: an update for 2005.
The hallmark pathologic feature of Parkinson's disease is loss of melanized dopaminergic neurons within the substantia nigra pars compacta coupled with depletion of striatal dopamine. This is responsible for the major motor features of the disease. Whereas dopaminergic replacement therapy is effective in the early stages of the illness, chronic treatment is associated with motor complications and development of features that do not respond to levodopa therapy. Development of cellular therapies offers the potential to provide more effective treatment for the disease without motor complications. Two clinical trials of fetal nigral transplantation failed to meet their primary endpoint and were complicated by the development of dyskinesia that persisted after withdrawal of levodopa ('off-medication' dyskinesia). However, recent studies suggest that both the limited clinical response and off-medication dyskinesia may be related to partial, but incomplete, dopaminergic reinnervation of the striatum and that both might be improved by transplantation of more dopamine neurons. Stem cells offer the potential to provide a virtually unlimited supply of optimized dopaminergic neurons that can provide enhanced benefits in comparison to fetal mesencephalic transplants. Stem cells have now been shown to be capable of differentiating into dopamine neurons that provide benefits following transplantation in animal models of Parkinson's disease. However, cell survival and behavioral responses are limited. There have been numerous advances in enhancing the yield of dopamine neurons from stem cells, and promoting their survival and consequent clinical effects. Stem cells offer great promise as a therapy for Parkinson's disease, but numerous hurdles remain to be overcome with stem cell therapy. The adverse event profile of transplantation must be determined, and societal and ethical issues addressed. As Parkinson's disease involves degeneration of both dopaminergic and non-dopaminergic neurons, it also remains to be determined if transplantation of even the ideal dopamine neuron will improve non-dopaminergic features of the disease or provide benefits superior to existing therapies.


Anomalously large capacitance of an ionic liquid described by the restricted primitive model.
We use Monte Carlo simulations to examine the simplest model of a room-temperature ionic liquid (RTIL), called the "restricted primitive model," at a metal surface. We find that at moderately low temperatures the capacitance of the metal-RTIL interface is so large that the effective thickness of the electrostatic double layer is up to three times smaller than the ion radius. To interpret these results we suggest an approach which is based on the interaction between discrete ions and their image charges in the metal surface and which therefore goes beyond the mean-field approximation. When a voltage is applied across the interface, the strong image attraction causes counterions to condense onto the metal surface to form compact ion-image dipoles. These dipoles repel each other to form a correlated liquid. When the surface density of these dipoles is low, the insertion of an additional dipole does not require much energy. This leads to a large capacitance C that decreases monotonically with voltage V, producing a "bell-shaped" curve C(V). We also consider what happens when the electrode is made from a semimetal rather than a perfect metal. In this case, the finite screening radius of the electrode shifts the reflection plane for image charges to the interior of the electrode, and we arrive at a "camel-shaped" C(V). These predictions seem to be in qualitative agreement with experiment.


Laboratory diagnosis of lupus anticoagulants for patients on oral anticoagulant treatment. Performance of dilute Russell viper venom test and silica clotting time in comparison with Staclot LA.
The detection of lupus anticoagulant (LA) in plasmas from patients on oral anticoagulants is problematic because of their prolonged clotting times. Mixing of patients and normal plasmas prior to testing for LA is employed to overcome this problem. We investigated the diagnostic efficacy of silica clotting time (SCT) and dilute Russell viper venom test (dRVVT) performed at low and high phospholipid concentrations, to diagnose LA in patients on oral anticoagulants, in comparison with Staclot LA (Stago) performed with and without hexagonal phospholipids and normal plasma. Case materials were 114 filtered plasmas from patients on oral anticoagulants with (n = 62) and without (n = 52) the antiphospholipid syndrome. Plasmas were considered LA-positive when Staclot LA (taken as the "gold standard") was diagnostic for LA. Forty-four plasmas were positive with Staclot LA. Forty and 39 of these were also positive with SCT and dRVVT (sensitivity relative to Staclot LA was 91% and 89%, respectively). Seventy plasmas were negative with Staclot LA. Three of these were positive with both SCT and dRVVT (specificity relative to Staclot LA was 96%). Kappa values for measure of agreement were 0.87 and 0.85 (p <0.001), respectively. In conclusion, SCT and dRVVT performed at low and high phospholipid concentrations without normal plasma can be considered as reliable as Staclot LA performed with hexagonal phospholipids and normal plasma to diagnose LA in patients on oral anticoagulants. Advantages of SCT and Drvvt over Staclot LA are easy automation, no need for normal plasma and relatively low cost.


[RANKL as a target molecule for treatment of joint destruction].
Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized progressive joint destruction. Recent studies have revealed an essential role of receptor activator of NF-kappaB ligand (RANKL) in bone destruction in RA, and therapeutics targeting RANKL has been attracting a great deal of attention.


Effects of elevated temperature and mobile phase composition on a novel C18 silica column.
A novel polydentate C18 silica column was evaluated at an elevated temperature under acidic, basic, and neutral mobile phase conditions using ACN and methanol as the mobile phase organic modifier. The temperature range was 40-200 degrees C. The mobile phase compositions were from 0 to 80% organic-aqueous v/v and the mobile phase pH levels were between 2 and 12. The maximum operating temperature of the column was affected by the amount and type of organic modifier used in the mobile phase. Under neutral conditions, the column showed good column thermal stability at temperatures ranging between 120 and 200 degrees C in methanol-water and ACN-water solvent systems. At pH 2 and 3, the column performed well up to about 160 degrees C at two fixed ACN-buffer compositions. Under basic conditions at elevated temperatures, the column material deteriorated more quickly, but still remained stable up to 100 degrees C at pH 9 and 60 degrees C at pH 10. The results of this study indicate that this novel C18 silica-based column represents a significant advancement in RPLC column technology with enhanced thermal and pH stability when compared to traditional bonded phase silica columns.


Manipulation of disulfide bonds differentially affects the intracellular transport, sorting, and processing of neuroendocrine secretory proteins.
To investigate if the prevention of disulfide bond formation affects the intracellular transport, sorting, and processing of a distinct set of neuroendocrine proteins in the regulated secretory pathway, we have treated Xenopus intermediate pituitaries with the thiol-reducing agent dithiothreitol. Pulse-chase incubations in combination with immunoprecipitation analysis were used to monitor the fates of the prohormone proopiomelanocortin (POMC), prohormone convertase PC2 and its helper protein 7B2, as well as secretogranin III. Manipulation of the disulfide bonds in POMC and proPC2 blocked their transport to the trans-Golgi network and strongly inhibited their processing. Reduction of the single disulfide bond in 7B2 did not disturb its transport and cleavage, but caused its missorting to the constitutive secretory pathway. Moreover, the liaison between proPC2 and 7B2 was prevented. Dithiothreitol did not affect transport, sorting, and cleavage of secretogranin III, which lacks disulfide bonds. When the reducing agent was washed away, POMC processing, proPC2 maturation, and the association between proPC2 and 7B2 were reestablished. Collectively, our findings indicate that manipulation of disulfide bonds differentially affects the fates of neuroendocrine proteins during their transit through the secretory pathway.


The structure of SV 40 chromatin.
Simian virus 40 (SV40) nucleoprotein complexes were studied with the electron microscope. Depending on the isolation procedure, SV40 chromatin has two different conformations: complexes isolated in the presence of 0.15 M NaCl appeared as very compact globular structures, while those isolated in the presence of 0.6 M NaCl had the typical 'beads-on-a-string' appearance of the primary nucleofilament. Concomitant with this structural change was a variation in the histone pattern and sedimentation behaviour of the complexes: with NaCl at 0.15 mol 1(-1) the isolated complexes contained both the nucleosomal histones and histone H1, and sedimented in sucrose gradients at 70S. Increasing the ionic strength to 0.6 M NaCl resulted in the removal of histone H1 from the complexes and in a decrease of the sedimentation coefficient to 40S. DNA relaxing enzyme is associated with the SV40 nucleoprotein complexes. The numbers of superhelical turns in DNA from compact and open types of complexes were found to be the same. Therefore the transition from the condensed to the open structure of viral chromatin does not require a change in the topological winding number of its DNA.


Effects of an art-based curriculum on clinical trials attitudes and breast cancer prevention knowledge.
Although Latinos now comprise the largest minority in the U.S. population, they continue to be seriously underrepresented in clinical trials. A nonrandomized controlled study of an innovative community-developed clinical trial and breast cancer education program targeting Latinas tested whether use of an art-based curriculum could increase willingness to enroll in six clinical trial scenarios and increase breast health and clinical trial knowledge. The art-based curriculum resulted in a larger increase in stated willingness to enroll across all clinical trial scenarios, and the difference was statistically significant (p<.05) in three. Breast health and clinical trials knowledge increased similarly and significantly for both groups. The results of this study show promise for the use of a community-developed art-based curriculum in the Latina population to increase willingness to enroll in clinical trials.


Isolation of mouse bone marrow neutrophils by light scatter and autofluorescence.
Murine bone marrow and blood cells have been analyzed and fractionated using an automated FACS II cell sorter. Using visible light scattered in the direction of (0 degrees) and perpendicular to (90 degrees) the laser beam it was possible to enrich for neutrophils (84%), immature myeloid cells (47%), and monocytes (78%). The enrichment for neutrophils was improved to 92% by using the light scattered by ultraviolet laser light (ca.360 nm). The autofluorescence at these wavelengths proved useful for obtaining further enrichment (to 97%). Indeed, three parameter sorting with 0 degrees and 90 degrees light scatter as well as autofluorescence also allowed the separation of lymphocytes (95%) and immature myeloid cells (89%). The same procedures could be applied for the isolation of neutrophils from mouse peripheral blood.


Transcriptome-wide characterization of miRNA-directed and non-miRNA-directed endonucleolytic cleavage using Degradome analysis under low ambient temperature in Phalaenopsis aphrodite subsp. formosana.
Plant microRNAs (miRNAs) regulate gene expression through post-transcriptional gene silencing. Phalaenopsis aphrodite subsp. formosana is an orchid species native to Taiwan, which has high economic value and a high frequency of floral polymorphism. To date, few studies have focused on the regulatory roles of miRNAs and functional small RNAs (sRNAs) in orchids although understanding the regulation of flower development and flowering time is potentially important. Here, we combined analyses of the transcriptome, sRNAs and the degradome to identify sRNA-directed transcript cleavages in Phalaenopsis. Degradome analysis provided large-scale evidence of conserved and novel miRNA-directed cleavage of target transcripts, and 46 abundant sRNA groups and their target transcripts were identified. Low temperature-responsive sRNAs were validated with normalized reads from an sRNA library and quantitative stem-loop reverse transcription-PCR (RT-PCR) analysis. According to gene ontology (GO) categorization, target transcripts of the novel miRNAs and sRNAs are functionally involved in metabolic processes or responses to stress. One particular homologous gene, Allcontig28452, which encodes digalactosyldiacylglycerol synthase 2 (DGD2), was found to be targeted by natural antisense transcripts (NATs) unique to Phalaenopsis. In summary, comprehensive analyses of the transcriptome, sRNAs and degradome using deep sequencing technology provided a useful platform for investigating miRNA-directed and non-miRNA-directed endonucleolytic cleavage in a non-model plant, the orchid Phalaenopsis.


Cutaneous metastases from a gastrointestinal stromal tumor of the stomach: review of literature.
Gastrointestinal stromal tumors (GIST) are neoplasms of mesenchymal origin which may or may not be malignant. Malignant GIST rarely metastasize to distal organs. A case of cutaneous metastasis from GIST has been presented. This case is particularly interesting because not only did the patient have multiple metastases from GIST, but eventually developed cutaneous metastasis. This phenomenon has not been reported in the literature. The most current literature on gastrointestinal stromal tumors has been reviewed.


Decreased angiotensin II binding affinity and binding capacity in the anterior pituitary gland of adult spontaneously hypertensive rats.
Angiotensin II (ANG) binding sites were quantified in single pituitary glands from 4-week-old and 14-week-old male spontaneously hypertensive rats (SHR) and age-matched male normotensive Wistar-Kyoto (WKY) control rats after incubation with 125I-[Sar1]-ANG, autoradiography with computerized densitometry, and comparison to 125I-standards. The maximum binding capacity (Bmax) decreased while the dissociation constant (Kd) for ANG increased in 14-week-old SHR when compared to age-matched WKY control rats (Bmax: 265 +/- 9 and 224 +/- 4 fmol/mg protein; Kd: 0.79 +/- 0.04 and 1.14 +/- 0.08 10(-9) M in WKY and SHR, respectively). Conversely, no difference between rat strains was found in 4-week-old animals. Our results suggest that pituitary ANG binding sites may play a role in the pathophysiology of established genetic hypertension.


Severe hemolytic reaction due to anti-JK3.
A 35-year-old gravida 3, para 3 Filipino woman with a negative antibody screen, no prior history of transfusion, and no hemolytic disease of the newborn in her children suffered a massive postpartum hemorrhage requiring transfusion. A severe hemolytic transfusion reaction occurred 5 days after delivery. Subsequently, a panagglutinin on a routine antibody identification panel was identified as anti-Jk3. The patient's red blood cell phenotype was Jk(a-b-) and all of her children were Jk(a-b+), yet the antibody that formed reacted with equal strength against all Jk(a)- or Jk(b)-positive cells. The rare Jk(a-b-) phenotype is more common in Polynesians. Anti-Jk3, like other Kidd system antibodies, is difficult to detect because in vivo production may be absent between provocative episodes and because these antibodies often show weak in vitro reactions. The increasing numbers of Pacific Islanders in the United States could result in more frequent encounters with this rare phenotype. Increased awareness of ethnic variability in blood phenotypes and of the capricious nature of Kidd antibodies can help pathologists and technologists deal more effectively with these cases.


Phylogeny of putative cholinergic visual pathways through the pretectum to the hypothalamus in teleost fish.
Three patterns of pretectal organization can be discerned morphologically in teleosts. The taxonomic distribution of these pretectal patterns suggests that the intermediately complex pattern (seen in most teleost groups) has given rise to both the elaborate pattern (seen in percomorphs) and the simple pattern (seen in cyprinids). Two pretectal patterns (intermediately complex and elaborate) form part of similar, homologous visual pathways to the hypothalamus; the third pattern is involved in a nonhomologous pathway to the hypothalamus. Acetylcholinesterase (AChE) histochemistry was used in the present study in order to characterize these pretectal patterns further. It is demonstrated that AChE is a highly selective and reliable interspecific marker for all divisions of the superficial pretectum, the nucleus corticalis, the posterior pretectal nucleus (or nucleus glomerulosus) and portions of the inferior lobe. Therefore, the histochemical data support the hypothesis of a homology between the three patterns of pretectal organization in teleosts. Furthermore, the present data provide a basis for more specific investigations regarding the involvement of acetylcholine as a neurotransmitter within the visual pathways to the hypothalamus in teleosts.


Chromosomal abnormalities in sperm.
The use of FISH (fluorescent in situ hybridization) in decondensed sperm nuclei has allowed, during the last decade, to indirectly study the chromosome constitution of human spermatozoa. Studies in control populations have been used to set up the basal level of aneuploidy for all human chromosomes and, based on conservative estimates, the percentage of chromosomally abnormal sperm in the general population could be considered to be at least 6.7%. In carriers of sex chromosome numerical anomalies and in severe oligozoospermic males (both frequent candidates for intracytoplasmic sperm injection), in structural chromosome carriers (enrolled in preimplantation genetic diagnosis programs) and in couples with recurrent miscarriage, sperm chromosome analyses by FISH could help to better establish a reproductive prognosis.


Should We Promote Catch-Up Growth or Growth Acceleration in Low-Birthweight Infants?
The idea that catch-up growth or growth acceleration has adverse effects on long-term health has generated much debate. This pattern of growth is most commonly seen after birth in infants of low birthweight; a global problem affecting over 20 million newborns a year. Faster postnatal growth may have short-term benefits but increases the long-term risk of aging, obesity and metabolic disease. Consequently, the optimal pattern of postnatal growth is unclear and is likely to differ in different populations. In infants born prematurely, faster postnatal growth improves long-term cognitive function but is associated with later risk factors for cardiovascular disease. So, on balance, the current policy is to promote faster growth by increasing nutrient intake (e.g. using higher-nutrient preterm formulas). Whether the same policy should apply to larger preterm infants is not known. Similarly, in infants from impoverished environments, the short-term benefits of faster postnatal growth may outweigh long-term disadvantages. However, whether similar considerations apply to infants from countries in transition is uncertain. For term infants from developed countries, promoting catch-up growth by nutritional supplementation has few advantages for short- or long-term health. Overall therefore, a 'one size fits all' solution for the optimal pattern of postnatal growth is unlikely.


Texture-based classification of liver fibrosis using MRI.
To investigate the ability of texture analysis of MRI images to stage liver fibrosis. Current noninvasive approaches for detecting liver fibrosis have limitations and cannot yet routinely replace biopsy for diagnosing significant fibrosis. Forty-nine patients with a range of liver diseases and biopsy-confirmed fibrosis were enrolled in the study. For texture analysis all patients were scanned with a T2 -weighted, high-resolution, spin echo sequence and Haralick texture features applied. The area under the receiver operating characteristics curve (AUROC) was used to assess the diagnostic performance of the texture analysis. The best mean AUROC achieved for separating mild from severe fibrosis was 0.81. The inclusion of age, liver fat and liver R2 variables into the generalized linear model improved AUROC values for all comparisons, with the F0 versus F1-4 comparison the highest (0.91). Our results suggest that a combination of MRI measures, that include selected texture features from T2 -weighted images, may be a useful tool for excluding fibrosis in patients with liver disease. However, texture analysis of MRI performs only modestly when applied to the classification of patients in the mild and intermediate fibrosis stages.


[Assisted evaluation scale of quality of life].
The TEAQV (Tableau d'évaluation assistée de qualité de vie) is an instrument designed to standardize the collection of quality of life data among patients with chronic psychiatric or somatic diseases. This instrument is a two-part. 7 point-scale (0 = extremely bad; 6 = excellent), self-rated quantitative evaluation of quality of life at different time points in 4 areas (physical and psychological well-being, family relationships, professional activity). The first part is a one time retrospective lifetime evaluation whereas the second part is a current state evaluation that can be prospectively repeated. Time points are determined by important periods during the illness or treatment course. This instrument is administered by a trained interviewer in 5 to 10 minutes. The TEAQV has been used in different populations. Correlation coefficients between TEAQV current state and conventional scales were studies. Among 26 lung and heart-lung transplant patients, the correlation coefficients between TEAQV and the Sickness Impact Profile are: physical: -.622; psychological: -.406. Among 18, treated, opioid dependent patients, the correlation coefficients between TEAQV and the Addiction Severity Index are: physical: -.548; psychological: -.763; social professional: -.747; family: -.341. Our early results with the TEAQV suggest that it is an easy to use and beneficial instrument to assess quality of life.


Effect of white matter hyperintensities on cortical cerebral blood volume using perfusion MRI.
White matter hyperintensities (WMHs) are commonly seen on brain magnetic resonance imaging (MRI) scans of elderly individuals, but their functional significance remains controversial. We used perfusion-weighted MRI to determine the impact of WMHs on cortical regional cerebral blood volume (rCBV). We studied 24 elderly stroke patients and 27 control subjects with conventional MRI which included T2-weighted FLAIR coronal slices through whole brain and gadolinium-DTPA (0.2 mmol/kg)-based perfusion MRI (pMRI) with echo planar imaging. Volumes of WMHs, including deep WMHs and periventricular hyperintensities (PVHs), were computed by an automated method after excluding regions of infarction. Partial correlations between WMH and corresponding cortical rCBV were determined after correction for age and atrophy. The relative rCBV of gray matter was higher in control subjects and there was no significant hemispheric asymmetry. When both stroke and control groups were included, there were significant correlations among frontal cortical rCBV and frontal WMHs, temporal cortical rCBV with temporal WMHs, and cortical rCBV with both total deep WMHs and PVHs. Although the trends of correlation still existed when the two groups were analyzed separately, they were not significant. The correlations between cortical rCBV and WMHs in the same lobe were significant for subjects with more severe hyperintensities irrespective of the group. In conclusion, T2-weighted WMHs are associated with reduced rCBV in the cerebral cortex, particularly in individuals with extensive hyperintensities.


phase instability and molecular kinetics provoked by repeated crossing of the demixing transition of PNIPAM solutions.
The demixing process of aqueous poly(N-isopropylacrylamide) (PNIPAM) solutions can occur either via a nucleation and growth process or via spinodal decomposition. The ensuing self-assembly, leading to heterogeneous morphologies within the PNIPAM solution, is codetermined by kinetic processes caused by molecular transport. By subjecting PNIPAM solutions to cyclic changes in temperature leading to repeated crossing of the demixing transition, we are able to assess the importance of kinetics as well as of overheating and supercooling of the phase transition within the metastable range delimited by the binodal and spinodal lines. First indications about the location of these stability limits for the low- and high-temperature phases, separated by about 1.6 K, could be gained by detailed kinetic studies of the refractive index. These investigations are made possible due to the novel technique of temperature-modulated optical refractometry.


History of shoulder instability surgery.
The surgical management of shoulder instability is an expanding and increasingly complex area of study within orthopaedics. This article describes the history and evolution of shoulder instability surgery, examining the development of its key principles, the currently accepted concepts and available surgical interventions. A comprehensive review of the available literature was performed using PubMed. The reference lists of reviewed articles were also scrutinised to ensure relevant information was included. The various types of shoulder instability including anterior, posterior and multidirectional instability are discussed, focussing on the history of surgical management of these topics, the current concepts and the results of available surgical interventions. The last century has seen important advancements in the understanding and treatment of shoulder instability. The transition from open to arthroscopic surgery has allowed the discovery of previously unrecognised pathologic entities and facilitated techniques to treat these. Nevertheless, open surgery still produces comparable results in the treatment of many instability-related conditions and is often required in complex or revision cases, particularly in the presence of bone loss. More high-quality research is required to better understand and characterise this spectrum of conditions so that successful evidence-based management algorithms can be developed. IV.


A New Method of Constructing a Drug-Polymer Temperature-Composition Phase Diagram Using Hot-Melt Extrusion.
Current experimental methodologies used to determine the thermodynamic solubility of an API within a polymer typically involves establishing the dissolution/melting end point of the crystalline API within a physical mixture or through the use of the glass transition temperature measurement of a demixed amorphous solid dispersion. The measurable "equilibrium" points for solubility are normally well above the glass transition temperature of the system, meaning extrapolation is required to predict the drug solubility at pharmaceutically relevant temperatures. In this manuscript, we argue that the presence of highly viscous polymers in these systems results in experimental data that exhibits an under or overestimated value relative to the true thermodynamic solubility. In previous work, we demonstrated the effects of experimental conditions and their impact on measured and predicted thermodynamic solubility points. In light of current understanding, we have developed a new method to limit error associated with viscosity effects for application in small-scale hot-melt extrusion (HME). In this study, HME was used to generate an intermediate (multiphase) system containing crystalline drug, amorphous drug/polymer-rich regions as well as drug that was molecularly dispersed in polymer. An extended annealing method was used together with high-speed differential scanning calorimetry to accurately determine the upper and lower boundaries of the thermodynamic solubility of a model drug-polymer system (felodipine and Soluplus). Compared to our previously published data, the current results confirmed our hypothesis that the prediction of the liquid-solid curve using dynamic determination of dissolution/melting end point of the crystalline API physical mixture presents an underestimation relative to the thermodynamic solubility point. With this proposed method, we were able to experimentally measure the upper and lower boundaries of the liquid-solid curve for the model system. The relationship between inverse temperature and drug-polymer solubility parameter (χ) remained linear at lower drug loadings. Significantly higher solubility and miscibility between the felodipine-Soluplus system were derived from the new χ values.


Dynamic coronary obstruction as a cause of angina pectoris: implications regarding therapy.
The strong link demonstrated at autopsy between coronary atherosclerosis and angina pectoris led to the important concept that a fixed obstruction of 1 or more coronary arteries was the pathophysiologic cause of angina: myocardial ischemia and angina occurred when myocardial oxygen demand out-stripped the capacity of the diseased coronary artery to deliver oxygen. Therapeutic strategies were based on attempts to lower myocardial oxygen needs induced by physical and emotional stress. However, the finding that dynamic increases in coronary vascular resistance can also either precipitate ischemia or reduce the threshold of myocardial oxygen consumption (MVO2) at which it occurs has profoundly altered our understanding of the pathophysiologic features of angina and, therefore, its treatment. Dynamic coronary obstruction can occur at the large-vessel level, causing Prinzmetal's or variant angina. It is also possible that in some patients a continuum of large-vessel coronary vasoconstrictor tone exists, causing the common clinical situation manifested by angina with variable thresholds of onset. Recent studies have demonstrated that increases in the resistance offered to flow by small coronary arteries too small to be imaged by angiography can also decrease anginal threshold. The fact that ischemia can be precipitated by dynamic increases in large- or small-vessel coronary resistance has important implications for the therapy of angina pectoris. In those persons who mostly have a dynamic component contributing to their coronary obstruction, primary intervention with vasodilator therapy, including nitrates and calcium-channel blocking agents, are probably most effective therapeutically.(ABSTRACT TRUNCATED AT 250 WORDS)


Broadband high-optical-density filters in the infrared.
A new concept for the design of broadband (2-25 microm and beyond) neutral-density filters in the infrared region without étaloning effects is proposed and demonstrated. One important aspect of the technique is to use metallic-thin-film (10-200-nm-thick) multilayer combinations deposited onto different substrates (ZnSe, CdTe, Lexan). Neutral-density filters with optical densities as high as 4 are designed and built in the broadband region (2-25 microm). Another key innovation is the use of ultrathin substrates (~100 nm thick) for elimination of étaloning effects normally present in thick (>0.5-mm) substrates. Neutral-density filters with such ultrathin substrates are also designed and investigated.


Changes in human epithelial kidney cells induced by nordihydroguaiaretic acid in vitro.
Some chemical agents induce kidney cystic changes in vivo comparable to human multicystic kidney disease. The biochemical aspects of human tubular cells were analysed by in vitro culture in the presence of nordihydroguaiaretic acid (NDGA). The uptake of 3H-thymidine in cultured cells in the presence of NDGA was comparable with control cultures, while 3H-hydroxyproline incorporation produced elevated values. The results suggest that NDGA in vitro induces modifications which may be related only to the synthesis of basement membrane components.


Schizophrenic disorder in old age. I. Some demographic, social and clinical characteristics.
This study discussed 129 cases who were at the time of the investigation 65 years of age and older, and in whom during their life-time schizophrenic disorder was diagnosed. Using a modified P-86 questionnaire and SCAG scale, heteroanamnestic data and data available from the patients' medical histories, demographic, social, and clinical characteristics of this population were gathered. Among other things, the article shows that the present marital status is the result of psychiatric illness, that the trend of social upward mobility exists in this population as well, and that lesions of the sphere of interest are the result of the psychiatric disorder, while the lesions of the sphere of initiative are the consequences of ageing process. It is also found that in correlation with age the clinical picture of the schizophrenic disorder becomes less "clear", and that a trend of co-existence of affective disorders is present.


Multivariate spectral methods for the analysis of event-related brain potentials.
The purpose of this article is to present some useful mathematical models for the analysis of multiple electrode event-related brain potential (ERP) experiments. We describe a multivariate spectral method for eye-movement removal and we also describe a multivariate spectral method for the analysis of multiple lead repeated measures data. The complex T2 and the complex Behrens-Fisher Problem are also discussed. All of the above methods are applied to experimental ERP data for four electrodes, two groups and two repeated factors.


Distinct signaling properties identify functionally different CD4 epitopes.
The CD4 coreceptor interacts with non-polymorphic regions of major histocompatibility complex class II molecules on antigen-presenting cells and contributes to T cell activation. We have investigated the effect of CD4 triggering on T cell activating signals in a lymphoma model using monoclonal antibodies (mAb) which recognize different CD4 epitopes. We demonstrate that CD4 triggering delivers signals capable of activating the NF-AT transcription factor which is required for interleukin-2 gene expression. Whereas different anti-CD4 mAb or HIV-1 gp120 could all trigger activation of the protein tyrosine kinases p56lck and p59fyn and phosphorylation of the Shc adaptor protein, which mediates signals to Ras, they differed significantly in their ability to activate NF-AT. Lack of full activation of NF-AT could be correlated to a dramatically reduced capacity to induce calcium flux and could be complemented with a calcium ionophore. The results identify functionally distinct epitopes on the CD4 coreceptor involved in activation of the Ras/protein kinase C and calcium pathways.


Multidimensional coherent pulse addition of ultrashort laser pulses.
Spatially and temporally separated amplification and subsequent coherent addition of femtosecond pulses is a promising performance-scaling approach for ultrafast laser systems. Herein we demonstrate for the first time the application of this multidimensional scheme in a scalable architecture. Applying actively controlled divided-pulse amplification producing up to four pulse replicas that are amplified in two ytterbium-doped step-index fibers (6 μm core), pulse energies far beyond the damage threshold of the single fiber have been achieved. In this proof-of-principle experiment, high system efficiencies are demonstrated at both high pulse energies (i.e., in case of strong saturation) and high accumulated nonlinear phases.


In vitro secondary MLR. I. Kinetics of proliferation and specificity of in vitro primed responder cells.
We have examined the kinetics and specificity of secondary in vitro mixed lymphocyte reactions (MLR). With limited numbers of primed responder cells (PRC) in the presence of "excess antigen" it was possible to obtain proliferative responses that were proportional to the number of PRC initially placed in culture. The responding cells, after an initial lag period, seem to grow exponentially until day 3 of culture. The responses of PRC (with the strain combinations and culture conditions described in this report) seemed to be directed toward stimulator cell determinants whose expression was determined by genes in the I region of the MHC. In one case, the relevant incompatibilities could be further restricted to the I-A region. Although PRC responded best to stimulator cells sharing the I region with the priming stimulator cell, apparent cross-reactivity could be observed by restimulating PRC with stimulator cells that did not carry the MHC haplotype of the priming stimulator cell. The rate of proliferation (measured as 3H-thymidine incorporation) in these apparent cross-reactions was reproducible and comparable to the rate observed in response to the priming stimulator cell. It was possible, therefore, to estimate the proportion of PRC that reacted in the presence of third party stimulator cells compared to the response of these PRC to the priming stimulator cells. We have estimated that the response of A (B6) PRC against H-2d and H-2s haplotype stimulator cells is about half of the response of these PRC to H-2b, the priming stimulator cell.


[An experimental study on chemoprevention of esophageal adenocarcinoma by celecoxib, a selective cyclooxygenase-2 inhibitor].
To study the feasibility of chemoprevention of esophageal adenocarcinoma by celecoxib, a selective cyclooxygenase-2(COX-2) inhibitor using a rat model. Rats were divided into 3 groups: model group, celecoxib group, and control group. The rat surgical model was established by performing a gastrojejunostomy plus an esophagojejunostomy 5 mm distal to the gastrojejunal anastomosis. Twenty-eight weeks after surgery, all the animals were sacrificed and the pathological changes in the esophagus were examined macroscopically. COX-2 expression was analyzed by immunohistochemistry. Prostaglandin E2(PGE2) level was measured by enzyme-linked immunosorbent assay(ELISA). The incidence of Barrett's esophagus and esophageal adenocarcinoma in the model group was 84% and 57% respectively, significantly higher than those in the control group(P<0.01). The incidence of esophageal adenocarcinoma in the celecoxib-treated group was significantly lower than that in the model group(P<0.01), and no esophageal adenocarcinoma was detected in the control group. COX-2 expression was detected in 100% of reflux esophagitis, Barrett esophagus and esophageal adenocarcinoma, but not found in the normal tissue from the esophagus and the jejunum(P<0.01). The PGE2 level in the esophageal tissue in the model group was significantly higher than that in the control group(P<0.01). Rats in the celecoxib-treated group had significantly lower PGE2 level than that in the model group(P<0.01). The PGE2 levels were significantly higher in rats with cancer than those without cancer(P<0.01). Celecoxib successfully prevents the development of esophageal adenocarcinoma in a rat surgical model with mixed reflux of acid and duodenal juice and significantly decreases the risk of Barrett esophagus developing esophageal adenocarcinoma. COX-2 maybe an effective selective target of chemoprevention for esophageal adenocarcinoma.


An interlaboratory comparison of transformation in Syrian hamster embryo cells with model and coded chemicals.
Three independent laboratories tested eight "model" and five coded chemicals in the Syrian hamster embryo clonal transformation assay system to establish the intra- and interlaboratory reproducibility of the system and to identify sources of variability. When a common cell pool and the same lot of fetal calf serum were used, the three laboratories obtained consensus on the activity of eight model chemicals: five chemicals (benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene, N-methyl-N'-nitro-N-nitrosoguanidine, nitroquinoline-N-oxide, and lead chromate) induced morphological transformation without exogenous metabolic activation and three (N-2-fluorenylacetamide, pyrene, and anthracene) produced no transformation response. Five coded chemicals (2,6-dichloro p-phenylenediamine, 4,4'-oxydianiline, cinnamyl anthranilate, dichlorvos, and reserpine), representative of environmental chemical classes, but not necessarily strong carcinogens, produced more equivocal responses in this interlaboratory study. Thus, while the assay can be used to distinguish between transforming and nontransforming chemicals in some cases, the intrinsic limitations in low transformation frequency and in achieving any dose-response results are major constraints to the use of this system in a routine testing program at the present time. Efforts to increase the transformation frequency or to amplify the expression of the transformed phenotype constitute some of the approaches which should be explored in order to overcome these limitations.


Decreased phosphorylation of STAT-1, STAT-4 and cytokine release in MDR-TB patients with primary resistance.
We recently showed that treatment failure rate was higher among multidrug-resistant tuberculosis (MDR-TB) patients without a previous history of tuberculosis (TB) treatment, or so-called 'primary resistance'. To investigate the phosphorylation levels of signal transducers and activators of transcription-1 (STAT-1) and STAT-4 and the subsequent cytokine release as a possible cause of a poor prognosis in MDR-TB patients with primary resistance. Ten patients with successfully treated pulmonary TB without resistance, 12 MDR-TB patients with acquired resistance and 10 MDR-TB patients with primary resistance were enrolled. After 24 h stimulation of peripheral blood mononuclear cells (PBMC) with interferon-gamma (IFN-gamma), interleukin-12 (IL-12), purified protein derivative (PPD), or lysate of Mycobacterium tuberculosis, flow cytometric analysis of intracellular pSTAT-1 and pSTAT-4 were performed and secretion of IFN-gamma, IL-12p40 and tumour necrosis factor-alpha (TNF-alpha) was measured in culture supernatant. The mean fluorescent intensities of pSTAT-1 and pSTAT-4 in PBMC of MDR-TB patients with primary resistance decreased on stimulation of IFN-gamma, PPD or lysate of M. tuberculosis when compared with patients with acquired resistance. In addition, secretion of IFN-gamma, IL-12p40 and TNF-alpha in these patients decreased on various stimuli. Decreased phosphorylation of STAT-1, STAT-4, and of subsequent cytokine release, might be associated with a poor prognosis in MDR-TB patients with primary resistance.


Glucose tolerance and physical activity level in people with spinal cord injury.
Cross-sectional, observational study. To evaluate the associations of physical activity and neurological lesion level with glucose tolerance in people with spinal cord injury (SCI). New South Wales, Australia. Twenty-five people (5 women, 20 men) with SCI (>6 months post-injury) aged between 18 and 65 years were recruited. Exclusion criteria included known coronary heart disease, stroke or diabetes. Participants underwent an oral glucose tolerance test. Fasting and 2-h plasma glucose concentrations were classified according to the World Health Organization categories of glycemia. Participants also completed the Physical Activity Scale for Individuals with Physical Disabilities and mean MET-hours day(-1) was calculated. Associations with the 2-h plasma glucose concentration were calculated through multiple and stepwise regressions. Participants presented with complete or incomplete tetraplegia (n=11 TETRA) or complete or incomplete paraplegia (n=14 PARA) with neurological lesion levels ranging from C3/4 to T12. Mean 2-h plasma glucose was 7.13+/-2.32 mmol l(-1). Nine participants had disordered glycemia (n=6 TETRA; n=3 PARA) and the remaining participants had normal glucose tolerance. Those participants with normal glucose tolerance participated in more moderate-vigorous and strength exercise and undertook more non-exercise-related mobility than those with disordered glycemia. Physical activity and age, but not lesion level were independent determinants of 2-h plasma glucose concentration (r=0.683, P=0.001), explaining 47% of the variance. Physical activity level is independently associated with glucose tolerance in people with SCI. Non-exercise activity may also be important for maintaining normal glycemia.


[1-14C]Arachidonic acid incorporation into glycerolipids and prostaglandin synthesis in peritoneal macrophages: effect of chloramphenicol.
Peritoneal macrophages from normal mice were labelled with [1-14C]arachidonic acid after 2 h culture. The uptake of arachidonic acid into cellular lipids was rapid, time-dependent and can be represented within the limit of the studied times by a parabolic regression. Indomethacin decreased the kinetics of uptake; this inhibition is dose-dependent. Chloramphenicol had no effect on macrophage [1-14C]arachidonic acid uptake. After 3 h, the radioactivity was recovered in phosphatidylcholine (38.6%), phosphatidylserine-phosphatidylinositol (8.5%), phosphatidylethanolamine (22.1%), diacylglycerol (2.9%), triacyglycerol (2%) and cholesteryl ester (11.8%). Chloramphenicol and indomethacin inhibited the labelling of phospholipids and stimulated the labelling of neutral lipids and cholesteryl ester. Studies on arachidonic acid release from glycerolipids of prelabelled 2-h cultured macrophages showed that phosphatidylcholine and phosphatidylserine-phosphatidylinositol are the major source of arachidonic acid in prostaglandin synthesis in macrophages stimulated or not by zymosan. Chloramphenicol inhibited release of fatty acid from phosphatidylcholine and phosphatidylserine-phosphatidylinositol; indomethacin had no effect. Both drugs inhibited prostaglandin synthesis in stimulated or non-stimulated macrophages. In the culture medium, indomethacin increased the release of free arachidonic acid by stimulated macrophages. Possible explanations for the mechanisms underlying these effects are presented. It is concluded that indomethacin and chloramphenicol exert profound effects on the metabolism of phospholipids and its zymosan activation. Chloramphenicol appears to impair prostaglandin synthesis through several mechanisms and especially through phospholipase inhibition.


Grid preparation for cryo-electron microscopy.
Once 2D crystals suitable for electron crystallography have been obtained, grid preparation for cryo-EM is a critical step in obtaining high-resolution structural information. Specimens have to be prepared in a manner that prevents dehydration and disruption of the crystals in the vacuum of the electron microscope. Sugar embedding is an effective way to preserve specimens in the native and hydrated state. Preparation of almost perfectly flat specimens is another prerequisite. Imperfect specimen flatness is a crucial problem in the recording of images and diffraction patterns at higher tilt angles because it causes the blurring of spots perpendicular to the tilt axis. In this chapter, we describe the protocols of preparing 2D crystal specimen for electron crystallographical data collection. These protocols cover preparation of a flat carbon support film by sparkless carbon evaporation, sugar embedding using back injection, and the recently developed carbon sandwich technique.


Simple determination of tin in biological materials by atomic absorption spectrometry with a graphite furnace.
A simple and rapid determination of tin in biological materials (blood, brain, liver, kidney, etc,) by atomic absorption spectrometry (AAS) with a graphite furnace is described. Suppression of interferences by direct addition of ascorbic acid in wet-ashed biological materials was investigated for the determination of tin. This method involves no extraction with organic solvent for removal of the interferences, and therefore it is neither time consuming nor error prone, and is suitable for large sample sizes and small sample volumes. The limit of detection of this method is 0.002 microgram/mL, equivalent to a limit of detection in the materials of 0.02 microgram/g. The calibration graph is linear up to 1 microgram/mL of tin.


Antibacterial poly(ethylene oxide) electrospun nanofibers containing cinnamon essential oil/beta-cyclodextrin proteoliposomes.
A novel antibacterial packaging material was engineered by incorporating cinnamon essential oil/β-cyclodextrin (CEO/β-CD) proteoliposomes into poly(ethylene oxide) (PEO) nanofibers by electrospinning technique. Herein, PEO was a stabilizing polymer and used as electrospinning polymeric matrix for the fabrication of CEO/β-CD proteoliposomes nanofibers. The nanoliposomes were inlaid with protein are defined as proteoliposomes. Taking advantage of bacterial protease secreted from Bacillus cereus (B. cereus), the controlled release of CEO from proteoliposomes was achieved via proteolysis of protein in proteoliposomes. The CEO/β-CD inclusion complex was prepared by the aqueous solution method and characterized by Raman and FTIR spectroscopy. After the treatment of CEO/β-CD proteoliposomes nanofibers packaging, the satisfactory antibacterial efficiency against B. cereus on beef was realized without any impact on sensory quality of beef. This study demonstrated that the CEO/β-CD proteoliposomes nanofibers can significantly extend the shelf life of beef and have potential application in active food packaging.


Exercise, nutrition and you: an off-campus course for grades 2-12.
Since interest in science classes has declined recently and obesity, especially in youth, continues to increase, an exercise physiology-based course was taught in public parks to promote active-learning science and healthy living. The course emphasized and integrated exercise, nutrition, and health during a 3-h session. Following an introduction, five hands-on laboratory-based student modules were performed. Students performed respiratory, cardiovascular, temperature regulation, energy expenditure, oxygen uptake, and exercise modules. During most modules, the students made measurements at rest and during the performance of exercise at different intensities. The students were very involved and engaged in problem solving throughout the session. The program was given for 10 days to more than 500 students representing 18 classes from 10 different schools. Evaluations indicated that the program was a real-life science experience that gave the students a new understanding of how their bodies worked and the purpose of exercise. The students and teachers also experienced "school learning" put into action as the program fit well with their science curriculum.


Effects of Shredding or Treating Apple Leaf Litter with Urea on Ascospore Dose of Venturia inaequalis and Disease Buildup.
Ascospores produced on diseased leaves in the leaf litter constitute the primary inoculum causing scab in commercial apple orchards in the northeastern United States. Two sanitation practices, shredding the leaf litter with a flail mower and urea application, were evaluated for their potential to reduce the risk of primary scab. Three measures of a treatment's potential were made: leaf litter density was evaluated to determine reduction of the source or primary inoculum; trapped ascospores were counted to measure the reduction of primary inoculum; and scab lesions on trees and seedlings were counted to determine reduction in disease incidence and severity on leaves and fruit. The results show that in the northeastern United States, shredding the leaf litter in November or April will reduce the risk of scab by 80 to 90% if all of the leaf litter is shredded. If 10 to 35% of the leaf litter cannot be shredded because of the limited offset of the flail mower and spread of the tree canopy, then the risk of scab is reduced by 50 to 65%. Urea applied to the leaf litter in November (when approximately 95% of the leaves had fallen) reduced the number of ascospores trapped by 50%. Urea applied to the leaf litter in April (before bud break) reduced the number of ascospores trapped by 66%. The reductions are discussed in relation to a sanitation action threshold that links sanitation to a strategy that reduces the fungicide dose to control primary scab in an orchard assessed with a moderate amount of foliar scab the previous autumn.


Polyandrous behavior in Cerconota anonella Sepp (Lepidoptera: Oecophoridae).
Among insects polyandrous behavior is common and plays an important role in female reproductive output. The present study aimed to evaluate the mating frequency of the moth Cerconota anonella Sepp under laboratory conditions and to verify if polyandrous behavior is common in this species. Approximately 47% of females mated more than once. However they presented differences in the mating period (early or late). In general, precocious females were more frequent than late females (P < 0.001, Binomial test). Such results suggest that polyandry in C. anonella may be common in the field.


The in vitro distribution of halofantrine in human blood and Plasmodium falciparum-parasitised red blood cells.
The in vitro distribution of the antimalarial drug halofantrine was measured in drug-preincubated whole blood after separation of the blood cells from the plasma according to their type. In normal blood, halofantrine was mainly associated with plasma (85% of the total drug) and to a lesser degree with erythrocytes (11%). The drug accumulated in lymphocytes to an approximately 250-fold higher concentration than in normal erythrocytes, but this represented only a small fraction (1%) of the total drug. It was not significantly bound to thrombocytes (2%), lymphocytes (1%) or granulocytes (0.3%). The distribution of halofantrine into Plasmodium falciparum-parasitised red blood cells was measured at different parasite stages and with varying serum concentrations. Halofantrine accumulated in P. falciparum-parasitised red blood cells to concentrations up to 60-fold those found in normal erythrocytes. The amount of accumulated drug depended on the parasite stage and presence of serum, since mature parasites showed the highest accumulation, and serum reduced drug accumulation compared to incubation under standard cultivation conditions.


Referencing an article.
References attached to any piece of work, whether it is published or is part of an assignment, demonstrate the range of knowledge and level of thinking invested by the author in the article. The British Standards Institution (BSI 1989) defines a reference as a set of data describing a document, sufficiently precise and detailed to identify it and enable it to be located. The accuracy and completeness of references ensures that readers will be able to locate the material as easily as possible.


Long-term results of ORIF of condylar head fractures of the mandible: A prospective 5-year follow-up study of small-fragment positional-screw osteosynthesis (SFPSO).
Optimum treatment of condylar head fractures (CHF) remains subject to controversy. There are currently a variety of alternative techniques applied, data in literature are often inconsistent and especially systematic long-term data on results after treatment by open reduction and internal fixation (ORIF) have so far not been available. This study in hand is the first long-term prospective study of ORIF after CHF based on osteosynthesis with 1.7 mm small-fragment positional screws (SFPSO)via a retroauricular transmeatal approach (RA). The study made use of radiologic, anatomic and objective functional parameters (axiography and MRI) to assess vertical height, disk mobility, protrusive and translatory movement as well as potential physical complaints. Included were surgical long-term sequelae after RA, such as incidence of stenosis of the auditory canal, the facial nerve and resulting disturbance of facial skin sensitivity. Retroauricular scars were evaluated according to the Vancouver Scar Scale. Helkimo and RDC/TMD indices were applied for patient's self-assessment of quality of life aspects after ORIF via RA. The sample in the first follow-up trial (FFT) in the years 2003-2004 comprised 26 patients (36 CHF). 22 patients (31 CHF) were re-evaluated in a second follow-up trial (SFT) between 2006 and 2008. A reference collective (43 patients, 56 CHF) treated with ORIF from 1993 to 2000 mainly by mini- or microplates (MMP) served as a surgical control group. Five years after ORIF all fractured condyles (FC) continued to show stable anatomic restoration of the pre-trauma vertical height. FC treated with SFPSO exhibited a significantly superior range of motion (p < 0.05) of disk and condyle during mouth opening and protrusion compared to a previous MMP reference collective. Also, no difference was found between condylar mobility of FC five years after surgery and non-fractured condyles (NFC). SFPSO had thus successfully achieved a sustainable, stable physiological restoration of protrusive mobility of the articular disk and condyle. Remarkably, these long-term results were even slightly better in SFT vs. FFT (p < 0.05). Except for sporadically occurring minor complaints, the patients' subjective overall long-term perception of the success of the treatment was equally positive to the surgeons' objective assessment. This first long-term prospective follow-up study, based on objective assessment tools, demonstrates that in all cases the major goals of ORIF in CHF could be fully achieved. These goals are: restoration of vertical height viz. prevention of occlusal disorders, physiological function of disk and condyle as well as of the lateral pterygoid muscle. Accordingly, ORIF of CHF e.g. with SFPSO and via the RA secures both a long-term functionally and anatomically stable result and as best as possible pain-free result for the patient, a central prerequisite of optimum perceived HRQoL. The paper has been amended by an extensive review part that covers the current knowledge of the major surgical aspects regarding the treatment of condylar head fractures.


Perceptual strategies in prelingual speech segmentation.
Previous work has suggested that infants may segment continuous speech by a BRACKETING STRATEGY that segregates portions of the speech stream based on prosodic cues to their endpoints. The two present studies were designed to assess whether infants also can deploy a CLUSTERING STRATEGY that exploits asymmetries in transitional probabilities between successive elements, aggregating elements with high transitional probabilities and identifying points of low transitional probabilities as boundaries between units. These studies examined effects of the structure and redundancy of speech context on infants' discrimination of two target syllables using an operant head-turning procedure. After discrimination training on the target syllables in isolation, discrimination maintenance was tested when the target syllables were embedded in one of three contexts. Invariant Order contexts were structured to promote clustering, whereas the Redundant and Variable Order contexts were not. Thirty-six seven-month-olds were tested in Experiment I, in which stimuli were produced with varying intonation contours; 36 eight-month-olds were tested in Experiment 2, in which stimuli were produced with comparable flat pitch contours. In both experiments, performance of the three groups was equivalent in an initial 20-trial test. However, in a second 20-trial test, significant improvements in performance were shown by infants in the Invariant Order condition. No such gains were shown by infants in the other two conditions. These studies suggest that clustering may complement bracketing in infants' discovery of units of language.


Experimental evolution and gene knockout studies reveal AcrA-mediated isobutanol tolerance in Ralstonia eutropha.
Isobutanol (IBT) has attracted much attention from researchers as a next generation drop-in biofuel. Ralstonia eutropha is a gram-negative bacterium which naturally produces polyhydroxybutyrate (PHB), and has been reported to produce IBT after metabolic engineering. Similar to other microbes, R. eutropha experiences toxicity from branched-chain alcohols and is unable to grow in the presence of IBT concentrations higher than 0.5% (v v(-1)). Such low tolerance greatly limits the ability of R. eutropha to grow and produce IBT. In order to study toxicity to the cells, IBT-tolerant strains were developed by experimental evolution, revealing that two genes, previously described as being related to IBT tolerance in Escherichia coli (acrA and acrA6), also presented mutations in R. eutropha evolved strains. The effect on the physiology of the cells of in-frame deletions of each of these genes was assessed in wild type and engineered IBT-producing strains in an attempt to reproduce a tolerant phenotype. The mutant strains' ability to tolerate, consume, and produce IBT were also analyzed. Although deletions of acrA6 and acrA did not significantly improve R. eutropha growth in the presence of IBT, these deletions improved cell survival in the presence of high concentrations of IBT in the extracellular milieu. Moreover, an in-frame acrA deletion in an engineered IBT-producing R. eutropha enhanced the strain's ability to produce IBT, which could potentially be associated with enhanced survival at high IBT concentrations.


The oxidizing agent menadione induces an increase in the intracellular molecular oxygen concentration in K562 and A431 cells: direct measurement using the new paramagnetic EPR probe fusinite.
The intracellular molecular oxygen concentration in control and menadione-treated K562 (an erythroleukemic cell line that grows in suspension) and A431 (an epidermal carcinoma that grows in monolayer) cells was measured directly by using the new electron paramagnetic resonance (EPR) probe fusinite. Because the oxidizing agent menadione is known to damage mitochondria and the cytoplasmic membrane in other cell systems, before conducting measurements of oxygen concentration in K562 and A431 cells, it was necessary to establish injury in these systems as well. Consequently, morphological and flow cytometric analyses were conducted after menadione treatment. The data presented here show that the two cell lines are heavily damaged by menadione. Once this menadione-induced injury was demonstrated, measurements of oxygen concentration were carried out in both K562 and A431 cells. Treatment with this quinone induces a sharp increase in intracytoplasmic molecular oxygen in both cell lines (from about 1% to about 10 and 15% in K562 and A431 cells, respectively). In addition, to gain a more complete understanding of the effects of menadione on cells, the extracellular molecular oxygen concentration and the oxygen consumption rate were also measured in control and menadione-treated K562 cells. These measurements demonstrate that menadione treatment results in an increase in the extracellular oxygen concentration (from about 5% in controls to 15% in treated cells) as well as a decrease in the oxygen consumption rate (from about 10 ng O/min/10(6) cells in controls to 3 ng O/min/10(6) cells after menadione exposure). The importance of the new EPR probe fusinite in monitoring directly cellular functions in which oxygen is involved and the effects of menadione on cellular oxygen balance are discussed.


Assessment tools predicting fitness to drive in older adults: a systematic review.
This systematic review synthesizes the research on screening and assessment tools used to determine older adults' fitness to drive. After a comprehensive search of the literature targeting tools commonly used by occupational therapists, 64 studies were reviewed and synthesized. The evidence demonstrated that a single tool measuring cognition, vision, perception, or physical ability individually is not sufficient to determine fitness to drive. Although some tools have stronger evidence than others, this review supports using different and focused assessment tools together for specific medical conditions. Results indicate that behind-the-wheel assessment remains the gold standard for driving evaluation; however, emerging evidence for observation of complex instrumental tasks of daily living and driving simulation supports further investigation with these tools.


The sexual state of Aspergillus parasiticus.
The sexual state of Aspergillus parasiticus, a potent aflatoxin-producing fungus within section Flavi, is described. The production of nonostiolate ascocarps surrounded by a separate peridium within the stroma places the teleomorph in genus Petromyces. Petromyces parasiticus differs from P. alliaceus by its larger ascospores with finely tuberculate ornamentation. The anamorphic Aspergillus states of the two species differ in conidial head color and microscopic characters.


Hake fish bone as a calcium source for efficient bone mineralization.
Calcium is recognized as an essential nutritional factor for bone health. An adequate intake is important to achieve or maintain optimal bone mass in particular during growth and old age. The aim of the present study was to evaluate the efficiency of hake fish bone (HBF) as a calcium source for bone mineralization: in vitro on osteosarcoma SaOS-2 cells, cultured in Ca-free osteogenic medium (OM) and in vivo on young growing rats fed a low-calcium diet. Lithotame (L), a Ca supplement derived from Lithothamnium calcareum, was used as control. In vitro experiments showed that HBF supplementation provided bone mineralization similar to standard OM, whereas L supplementation showed lower activity. In vivo low-Ca HBF-added and L-added diet similarly affected bone deposition. Physico-chemical parameters concerning bone mineralization, such as femur breaking force, tibia density and calcium/phosphorus mineral content, had beneficial effects from both Ca supplementations, in the absence of any evident adverse effect. We conclude HBF derived from by-product from the fish industry is a good calcium supplier with comparable efficacy to L.


Differential diagnosis of personality disorders by the seven-factor model of temperament and character.
We used multiaxial structured interviews and questionnaires to evaluate the ability of self-reports on seven personality dimensions to predict independent interview diagnoses of DSM-III-R personality disorders. We studied 136 consecutive adult psychiatric inpatients, excluding those with psychosis, organic mental disorders, and severe agitation. Sixty-six patients had interview diagnoses of DSM-III-R personality disorders. Most also had mood disorders. We confirmed the hypotheses that self-reports of low self-directedness and cooperativeness strongly predicted the number of personality symptoms in all interview categories, whereas the other factors distinguished among subtypes as predicted. Self-directedness and cooperativeness also predicted the presence of any personality disorder by differentiating patients varying in risk from 11% to 94%. Patients in clusters A, B, and C were differentiated by low reward dependence, high novelty seeking, and high harm avoidance, respectively. We conclude that low self-directedness and cooperativeness are core features of all personality disorders and are validly measured by the seven-factor Temperament and Character Inventory, but not the five-factor Neuroticism-Extraversion-Openness inventory. Each DSM-III-R personality disorder category is associated with a unique profile of scores in the seven-factor model, providing an efficient guide to differential diagnosis and treatment.


Comparison of haemorrheological parameters and blood pressure in various breeds of dog.
Relationships between blood pressure and haemorrheological factors were examined in three groups of dogs characterised by different levels of blood pressure. The groups used were sight hounds (high pressure), retrievers (low pressure) and a mixed group with intermediate pressure. The three groups had different levels of haematocrit and blood viscosity at both high and low shear rates, with the sight hounds showing the highest and retrievers showing the lowest levels for each of the parameters. The plasma viscosities did not differ significantly between the groups. Blood pressure and blood viscosity or haematocrit were not correlated within dog groups, but when the dog groups were considered together, significant positive correlations existed between pressure and viscosity and pressure and haematocrit.


A variable pulse-burst electromagnetic generator for electrical stimulation of biological systems.
A variable frequency-burst type, electromagnetic pulse generator has been developed to optimize the effect of electrical stimulation on bone growth. Using a pair of coils, with 100 turns and 18-gauge wire, the instrument can generate a maximum magnetic field of 300 Gauss. Its pulse repetition frequency can be varied from 10 Hz to 2 KHz and the duty cycle, consisting of several short carrier frequency pulses, can be varied up to 95%. This design also permits the period of the carrier pulse to be changed.


Massively parallel femtosecond laser processing.
Massively parallel femtosecond laser processing with more than 1000 beams was demonstrated. Parallel beams were generated by a computer-generated hologram (CGH) displayed on a spatial light modulator (SLM). The key to this technique is to optimize the CGH in the laser processing system using a scheme called in-system optimization. It was analytically demonstrated that the number of beams is determined by the horizontal number of pixels in the SLM NSLM that is imaged at the pupil plane of an objective lens and a distance parameter pd obtained by dividing the distance between adjacent beams by the diffraction-limited beam diameter. A performance limitation of parallel laser processing in our system was estimated at NSLM of 250 and pd of 7.0. Based on these parameters, the maximum number of beams in a hexagonal close-packed structure was calculated to be 1189 by using an analytical equation.


Malignant lymphocytic lymphoma. Demonstration of a serum inhibitor of myelopoiesis and response to combination chemotherapy.
A case of diffuse well differentiated lymphocytic lymphoma with associated leukopenia, is described. The colony-forming unit (CFU-C) assay was used to quantitate myeloid precursor cells and to test for the presence of suppressor cells and/or serum factors inhibiting myeloid cell proliferation. Mild suppression of CFU-C was noted with the patient's bone marrow cells in coculture studies with normal marrow. The patient's serum, when added to the culture of normal bone marrow cells, produced a marked decrease in CFU-C. Treatment with combination chemotherapy (prednisone, cyclophosphamide, and vincristine) produced a clinical response with correction of the leukopenia. Post-treatment serum did not produce a significant reduction in CFU-C from normal bone marrow.


The diagnosis and management of vertical defects within the furcation.
This article describes two common varieties of osseous lesions within the furcation--hemifurcal and crescent-intrafurcal defects--and their appropriate management. Although hemifurcal lesions are difficult to assess both radiographically and clinically, once they are diagnosed, they can be readily resolvable using a self-regeneration procedure or an osseous graft. Crescent-intrafurcal defects are more common than hemifurcal lesions and can be discerned more easily on radiographs than clinically. The treatment of a crescent-intrafurcal defect focuses on minimizing the vertical component. Self-regeneration or osseous grafting is considered an appropriate treatment course.


Bioinspired Total Synthesis of (±)-Chaetophenol C Enabled by a Pd-Catalyzed Cascade Cyclization.
A novel Pd(II)-catalyzed cascade reaction has been developed that consists of a highly regio- and stereoselective oxa [4 + 2] cycloaddition reaction of o-alkynylbenzaldehydes and an intramolecular carboxylic group quenching of the in situ generated oxonium ion. This new reaction provides a one-step construction of the tetracyclic core structure of chaetophenol C from two simple starting materials. The developed chemistry was successfully applied to the first total synthesis of chaetophenol C and dozens of its analogues.


Working with people who have killed: the experience and attitudes of forensic mental health clinicians working with forensic patients.
Forensic mental health (FMH) clinicians sometimes feel unsupported and unprepared for their work. This article explores their experiences of working in a FMH setting in Australia. The research examined the clinical context of clinicians working with forensic patients (FP), particularly those individuals who have killed while experiencing a mental illness. A qualitative, exploratory design was selected. Data were collected through focus groups and individual interviews with hospital and community-based forensic clinicians from all professional groups: psychiatric medicine, social work, psychology, mental health nursing, occupational therapy, and psychiatric service officers. The main themes identified were orientation and adjustment to FMH, training in FMH, vicarious traumatization, clinical debriefing and clinical supervision, and therapeutic relationships. Participants described being frustrated and unsupported in making the transition to working with FP and felt conflicted by the emotional response that was generated when developing therapeutic relationships. Recommendations include the development of programmes that might assist clinicians and address gaps in service delivery, such as clinical governance, targeted orientation programmes, and clinical supervision.


[Selection of four surgical techniques in orthotopic liver transplantation].
To compare the advantages and disadvantages of four surgical techniques in orthotopic liver transplantation. A total of 135 adult recipients receiving cadaveric whole liver grafts were divided into four groups according to the surgeries they received: group A (n=22) underwent classic orthotopic liver transplantation, group B (n=79) underwent modified piggyback liver transplantation, group C (n=18) underwent classical piggyback liver transplantation, and group D (n=16) underwent modified classic orthotopic liver transplantation. The clinical data of these recipients were retrospectively analyzed. The operation time, anhepatic time, and intra-operation bleeding volume among these four groups were significantly different (P < 0.05). The incidence of transient renal damage in group C was significantly lower than that in other groups (P < 0.05), while the complication rates and survival rates were not significantly different in the early stage after the operation. Surgery techniques should be carefully selected based on the individual patients's pre-operative condition. The modified classic orthotopic liver transplantation is a preferred technique for tumor patients or patients with surgical history of upper abdomen.


[Diagnosis and therapy of temporomandibular disorders].
Temporomandibular disorders is a collective term covering a number of related disorders affecting the temporomandibular joints, masticatory muscles, and related structures. The study reviews the recent knowledge about the diagnosis and complex therapy of temporomandibular disorders on the basis of published scientific literature. The role of general dental practitioner in management of patients with temporomandibular disorders is emphasised. Since a lot of patients turn to them for a first consultation, they should be familiar with the main diagnostic aspects of these disorders. The non-invasive conservative therapeutic possibilities are described in detail and they are suggested in the initial phase of the treatment. The disorders, which usually need further consultations with other specialist, are also described.


Comparison of survival and tumor recurrence rates in patients undergoing liver transplantation for hepatitis B-related hepatocellular carcinoma using Milan, Shanghai Fudan and Hangzhou criteria.
To assess the performance of the Milan, Shanghai Fudan and Hangzhou criteria based on a preoperative evaluation in patients undergoing liver transplantation (LT) for hepatitis B-related hepatocellular carcinoma (HCC). Using a prospectively collected database, the data of consecutive patients with hepatitis B-related HCC undergoing LT at the Department of Liver Surgery of Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University from January 2005 to December 2009 were reviewed. Overall survival and tumor recurrence rates of patients fulfilling the Milan, Shanghai Fudan and Hangzhou criteria were compared using log-rank test. Altogether 148 patients were enrolled in the study, among whom 88 fulfilled the Milan criteria and 24 and 39 were beyond Milan but within the Shanghai Fudan or Hangzhou criteria, respectively. After a median follow-up of 44 months, survival rates did not differ among the three groups (P = 0.8780). Recurrence rates were significantly higher for newly eligible patients by the Shanghai Fudan or Hangzhou criteria compared with those within the Milan criteria. The Milan criteria should be used as the preferred criteria for the selection of hepatitis B-related HCC for LT. Considering the high tumor recurrence rates and donor scarcity, a moderate expansion of the Milan criteria must be performed cautiously until high-quality clinical trials are conducted.


The integrated nature of motor cortical function.
Recent studies on the functional organization and operational principles of motor cortical function, taken together, strongly support the notion that the motor cortex controls the muscle activities subserving movements in an integrated manner. For example, during pointing the shoulder, elbow and wrist muscles appear to be controlled as a coupled functional system, rather than individually and separately. The pattern of intrinsic connections between motor cortical points is likely part of the explanation of this operational principle. So too is the manner in which muscles and muscle synergies are represented in the motor cortex. However, selection of movement-related muscle synergies is likely a dynamic process involving the functional linking of a variety of motor cortical points, rather than the selection of fixed patterns embedded in the motor cortical circuitry. One of the mechanisms that may be involved in the functional linking of motor cortical points is disinhibition. Thus, motor cortical points are recruited into action by selected excitation as well as by selected release from inhibition. The incoordination of limb movements in patients after a stroke may be understood, at least in part, as a disruption of the connections between motor cortical points and of the neural mechanisms involved in their functional linking.


Development and validation of chiral high-performance liquid chromatographic methods for the quantitation of valsartan and of the tosylate of valinebenzyl ester.
A stereospecific HPLC method for the quantitation of CGP 49309 in samples of its corresponding enantiomer valsartan has been developed and validated. The enantiomeric separation was achieved on a 5 micron silica-bonded, alpha 1-acid glycoprotein column (Chiral AGP) with a phosphate buffer, pH 7, containing 2% (v/v) 2-propanol as a mobile phase. The linearity was established in the range 0.1-4% (r > 0.999). The limit of quantitation was 0.1% and the limit of detection was 0.04%. The accuracy of the method was found to be 96.7% (average). For the precision (repeatability), a relative standard deviation value of 2.4% was found. Similarly, a stereoselective HPLC method was also developed and validated for the quantitation of the enantiomer of the starting material used for the synthesis of valsartan, namely (R)-valinebenzyl ester tosylate. Baseline resolution of the enantiomers of valinebenzyl ester tosylate could be achieved on the chiral crown ether column Crownpak CR (Daicel) at 50 degrees C using water-methanol-trifluoroacetic acid (850:150:1, v/v) as a mobile phase. The linearity was established in the range 0.5-5% (r > 0.999). The accuracy of the method was found to be 100.5% (average). For the precision (repeatability), a relative standard deviation value of 3.4% was found. Both methods were found to be suitable for the analysis of the respective analytes.


Development of clinical scientists.
The education and training of clinical scientists has served society in several ways. For academic pharmacy, the emergence of clinical science has provided research and scholarship opportunities for clinical faculty development. Clinical scientists have also begun to play important roles in industrial drug research and development. For all faculty and students, clinical science research reinforces a "research mindset" that will become increasingly important as our society moves from a production/extraction to an information-based economy. Pharmacy will best evolve by increasing its commitment to clinical science research. In the process, academic pharmacy must continue to improve and support excellent education and training programs for clinical scientists.