Genome analyses of the new model protist Euplotes vannus focusing on genome rearrangement and resistance to environmental stressors.
As a model organism for studies of cell and environmental biology, the free-living and cosmopolitan ciliate Euplotes vannus shows intriguing features like dual genome architecture (i.e., separate germline and somatic nuclei in each cell/organism), "gene-sized" chromosomes, stop codon reassignment, programmed ribosomal frameshifting (PRF) and strong resistance to environmental stressors. However, the molecular mechanisms that account for these remarkable traits remain largely unknown. Here we report a combined analysis of de novo assembled high-quality macronuclear (MAC; i.e., somatic) and partial micronuclear (MIC; i.e., germline) genome sequences for E. vannus, and transcriptome profiling data under varying conditions. The results demonstrate that: (a) the MAC genome contains more than 25,000 complete "gene-sized" nanochromosomes (~85 Mb haploid genome size) with the N50 ~2.7 kb; (b) although there is a high frequency of frameshifting at stop codons UAA and UAG, we did not observe impaired transcript abundance as a result of PRF in this species as has been reported for other euplotids; (c) the sequence motif 5'-TA-3' is conserved at nearly all internally-eliminated sequence (IES) boundaries in the MIC genome, and chromosome breakage sites (CBSs) are duplicated and retained in the MAC genome; (d) by profiling the weighted correlation network of genes in the MAC under different environmental stressors, including nutrient scarcity, extreme temperature, salinity and the presence of ammonia, we identified gene clusters that respond to these external physical or chemical stimulations, and (e) we observed a dramatic increase in HSP70 gene transcription under salinity and chemical stresses but surprisingly, not under temperature changes; we link this temperature-resistance to the evolved loss of temperature stress-sensitive elements in regulatory regions. Together with the genome resources generated in this study, which are available online at Euplotes vannus Genome Database (http://evan.ciliate.org), these data provide molecular evidence for understanding the unique biology of highly adaptable microorganisms.


Pattern of pulmonary venous flow in patients with ostium secundum atrial septal defect.
The purpose of this study is to determine the possible influence of a left to right atrial shunt over the pulmonary venous flow pattern in children with ostium secundum atrial septal defect (ASD). Complete two-dimensional, spectral Doppler and colour flow Doppler examination were undertaken to examine the pulmonary vein flow pattern in 74 patients with ASD. This group was compared with a control group of 49 non-cardiological patients of similar ages and gender. Ultimately, pulmonary venous flow patterns changed. Pulmonary vein systolic velocities were significantly increased and diastolic velocities decreased in the ASD patient group compared with the control group. The right ventricular (RV) systolic function, evaluated by tricuspid annular displacement and tricuspid annular systolic velocity, was increased in patients with ASD. No left ventricular dysfunction was detected in the patient study group. Patients with ASD show changes in the pattern of pulmonary venous flow with an increase in systolic velocity and a decrease in diastolic velocities. This could be caused by an increase in the RV systolic function, which creates a vacuum effect against not only blood from the superior and inferior vena cavae, but also blood from the pulmonary vein through the ASD.


Properties of Decylammonium Chloride and Cesium Perfluorooctanoate at Interfaces and Standard Free Energy of Their Adsorption
Measurements of the surface tension of aqueous solutions of decylammonium chloride (DACl) and cesium perfluorooctanoate (CsPFO) and the interfacial tension of DACl (CsPFO) solution-decane and DACl (CsPFO) solution-benzene systems were made at 293 and 303 K. On the basis of these measurements, the adsorption isotherms and the standard free energies of adsorption were determined. Also, the standard free energy of adsorption was determined from the surface free energy of the tails of DACl and CsPFO and the interfacial free energy of the tail-water system. It was found that the standard free energy of adsorption at a given temperature only slightly depends on the type of phase in contact with the solutions of the surfactants and can be determined on the basis of the surface and interfacial free energy of systems including the tails of the surfactants. It was also found that standard free energy of adsorption depends on temperature, and is considerably smaller for CsPFO than for DACl. Copyright 1997Academic Press


Improving Documentation of Distress in Veteran Patients for Hematology/Oncology Clinics.
The purpose of this quality improvement study was to improve physician documentation of distress in medical records of hematology/oncology veteran patients at the Malcolm Randall Veteran Affairs (VA) Medical Center hematology/oncology fellows' clinic in Gainesville, Florida. Before this intervention, the VA hematology/oncology fellows were not documenting patient distress in medical records. The quality improvement intervention was executed through the use of Plan-Do-Study-Act (PDSA) cycles with an ultimate goal of 50% documentation rate. Physician charts were audited to investigate official documentation of distress in patient charts. Physician documentation of distress was 14% in the first PDSA cycle, 21% in the second PDSA cycle, and 36% in the third PDSA cycle. Additional data on distress in hematology/oncology veteran patients were collected using the National Comprehensive Cancer Network Distress Thermometer and Problem List for Patients. Analysis of findings indicated that 42% of 88 patients experienced distress. Findings also suggest that hematology/oncology veteran patients experience specific sources of distress, notably fatigue and pain. These patients have presumably undergone unique experiences that can result in distress that providers should follow-up with in medical charts. Although this intervention has proven challenging to fully implement, standardizing patient distress in patient medical records has the potential to improve the quality of care provided by hematology/oncology physicians.


Extraction of biogenic amines using sorbent materials containing immobilized crown ethers.
Three sorbent materials (A18C6-MS, DA18C6-MS and AB18C6-MS) based on the crown ether ligands, 1-aza-18-crown-6, 1,4,10,13-tetraoxa-7,16-diazacyclo octadecane and 4'-aminobenzo-18-crown-6, respectively, were prepared by the chemical immobilization of the ligand onto mesoporous silica support. The sorbents were characterized by FT-IR, scanning electron microscopy-energy dispersive X-ray microanalysis, elemental analysis and nitrogen adsorption-desorption test. The applicability of the sorbents for the extraction of biogenic amines by the batch sorption method was extensively studied and evaluated as a function of pH, biogenic amines concentration, contact time and reusability. Under the optimized conditions, all the sorbents exhibited highest selectivity toward spermidine (SPD) compared to other biogenic amines (tryptamine, putrescine, histamine and tyramine). Among the sorbents, AB18C6-MS offer the highest capacity and best selectivity towards SPD in the presence of other biogenic amines. The AB18C6-MS sorbent can be repeatedly used three times as there was no significant degradation in the extraction of the biogenic amines (%E>85). The optimized procedure was successfully applied for the separation of SPD in food samples prior to the reversed-phase high performance liquid chromatography separation.


Possible existence of two mechanisms involved in alpha 1-adrenergic action: effect of Sgd 101/75.
The effect of 2-(2-methyl-indazol-4-imino)-imidazoline (Sgd 101/75) on the rate of urea synthesis by isolated rat hepatocytes was studied. This agent was observed to stimulate ureagenesis through the activation of alpha 1-adrenoceptors (prazosin-sensitive). The effect of Sgd 101/75 was dependent on the presence of calcium and was not affected by insulin. The active phorbol ester, phorbol 12-myristate 13-acetate, blocked the effect of Sgd 101/75. It was also observed that this adrenoceptor agonist was unable to stimulate ureagenesis in hepatocytes obtained from hypothyroid rats but produced clear stimulation of this metabolic pathway in cells obtained from adrenalectomized rats. The data indicate that this agonist stimulates hepatic metabolism through a calcium-dependent, insulin-insensitive pathway for alpha 1-adrenergic action, modulated by the thyroid status of the animal.


Storytelling as part of cancer rehabilitation to support cancer patients and their relatives.
Previous research on psychosocial support for cancer-related concerns has primarily focused on either patients or their relatives, although limited research is available on how patients and their relatives can be supported together. The aim of this article is to explore the use of storytelling as a part of a residential cancer rehabilitation intervention for patients together with their relatives, with a specific focus on their management of cancer-related concerns. Ten pairs participated in the intervention and data were generated through ethnographic fieldwork, including participant observations, informal conversations and follow-up interviews conducted one month after completing the intervention. Analysis was performed drawing on narrative theory combined with social practice theory. The results demonstrate that the use of storytelling and metaphors intertwined with other course activities, such as dancing and arts & crafts, provided the patients and their relatives with strategies to manage cancer-related concerns, which they were later able to apply in their everyday lives. The study results may be useful to other professionals in clinical practice for rehabilitation purposes for addressing issues of fear and worry.


Regional and cellular expression of CYP2D6 in human brain: higher levels in alcoholics.
Cytochrome P450 (CYP) 2D6 is expressed in liver, brain and other extrahepatic tissues where it metabolizes a range of centrally acting drugs and toxins. As ethanol can induce CYP2D in rat brain, we hypothesized that CYP2D6 expression is higher in brains of human alcoholics. We examined regional and cellular expression of CYP2D6 mRNA and protein by RT-PCR, Southern blotting, slot blotting, immunoblotting and immunocytochemistry. A significant correlation was found between mean mRNA and CYP2D6 protein levels across 13 brain regions. Higher expression was detected in 13 brain regions of alcoholics (n = 8) compared to nonalcoholics (n = 5) (anovap < 0.0001). In hippocampus this was localized in CA1-3 pyramidal cells and dentate gyrus granular neurons. In cerebellum this was localized in Purkinje cells and their dendrites. Both of these brain regions, and these same cell-types, are known to be susceptible to alcohol damage. For one case, a poor metabolizer (CYP2D6*4/*4), there was no detectable CYP2D6 protein, confirming the specificity of the antibody used. These data suggest that in alcoholics elevated brain CYP2D6 expression may contribute to altered sensitivity to centrally acting drugs and to the mediation of neurotoxic and behavioral effects of alcohol.


[Palliative care for cancer patients with refractory ulcerating malignant skin tumors and skin metastases].
Coping with ulcerating or bleeding skin tumours or metastases not suitable for surgical, radiotherapeutical or chemotherapeutical treatment is a difficult problem for patients, doctors and nursing staff. The care should focus on limiting local and systemic infection, combating unpleasant smells and reducing bleeding. Palliative amputation is sometimes a solution. The treatment depends on the nature and site of the tumour, it should preferably be adapted to the individual patient and be carried out in consultation with the patient, the specialist in charge or the GP, and the (oncological) nurse. The purpose of all this is to optimize the quality of life in the terminal phase.


Phylogenetic methods in drug discovery.
In recent decades, growth of computing power has facilitated powerful techniques for reconstructing evolutionary relationships from online genetic and proteomic databases. These methods are useful tools for pharmacologists for analyzing relationships between receptors and associated enzymes. Phylogenetic analysis can help generate hypotheses and leads for experimentation. Reconstruction of molecular phylogenies for the nonspecialist is described in this article using the example of the orphaned g protein coupled receptor GPR18.


Review of highly charged heavy ion production with electron cyclotron resonance ion source (invited).
The electron cyclotron resonance ion source (ECRIS) plays an important role in the advancement of heavy ion accelerators and other ion beam applications worldwide, thanks to its remarkable ability to produce a great variety of intense highly charged heavy ion beams. Great efforts over the past decade have led to significant ECRIS performance improvements in both the beam intensity and quality. A number of high-performance ECRISs have been built and are in daily operation or are under construction to meet the continuously increasing demand. In addition, comprehension of the detailed and complex physical processes in high-charge-state ECR plasmas has been enhanced experimentally and theoretically. This review covers and discusses the key components, leading-edge developments, and enhanced ECRIS performance in the production of highly charged heavy ion beams.


Mycotoxins in Plant-Based Dietary Supplements: Hidden Health Risk for Consumers.
Mycotoxin contamination of dietary supplements represents a possible risk for human health, especially in the case of products intended for people suffering from certain health conditions. The aim of this study was to assess the extent of this problem based on analyses of a wide set of herbal-based dietary supplements intended for various purposes: (i) treatment of liver diseases (milk thistle); (ii) reduction of menopause effects (red clover, flax seed, and soy); and (iii) preparations for general health support (green barley, nettle, goji berries, yucca, etc.) The analytical method including 57 mycotoxins was based on a QuEChERS-like (quick, easy, cheap, effective, rugged, safe) approach and ultrahigh performance liquid chromatography coupled with tandem mass spectrometry. The main mycotoxins determined were Fusarium trichothecenes, zearalenone and enniatins, and Alternaria mycotoxins. Co-occurrence of enniatins, HT-2/T-2 toxins, and Alternaria toxins was observed in many cases. The highest mycotoxin concentrations were found in milk thistle-based supplements (up to 37 mg/kg in the sum).


Bone mineral density and grip strength in postmenopausal Turkish women with osteoporosis: site specific or systemic?
To assess the relationship of grip strength to site-specific bone mineral density of the metacarpal bone and also axial bone mineral density. The bone mineral density of the lumbar spine, femoral neck and the nondominant hand were measured by DEXA. A total of 187 postmenopausal women were included in the study. Of the patients, 102 were osteoporotic, and 85 were not osteoporotic and served as control subjects. Grip strength of the nondominant hand was measured by hand-held dynamometer. Skinfold thickness of the nondominant hand was measured by a caliper (Holstain). Biochemical markers of bone turnover and other osteoporosis-related variables were also measured. There was a statistically significant difference between groups regarding bone mineral density of the lumbar, femoral (neck) and hand regions and the grip strength (P < .05). Hand bone mineral density (BMD) was found to be correlated with bone mineral density of the lumbar and femoral (neck) regions in osteoporotic patients. Grip strength was correlated positively with the BMD of the nondominant hand. Grip strength was correlated negatively with age and years since menopause. Grip strength was also correlated positively with femoral neck BMD. The study provides support for a site-specific and also systemic relationship between muscle and bone. Grip strength is also a predictor of hand bone mineral density.


EMG Measurement with Textile-Based Electrodes in Different Electrode Sizes and Clothing Pressures for Smart Clothing Design Optimization.
The surface electromyography (SEMG) is one of the most popular bio-signals that can be applied in health monitoring systems, fitness training, and rehabilitation devices. Commercial clothing embedded with textile electrodes has already been released onto the market, but there is insufficient information on the performance of textile SEMG electrodes because the required configuration may differ according to the electrode material. The current study analyzed the influence of electrode size and pattern reduction rate (PRR), and hence the clothing pressure (Pc) based on in vivo SEMG signal acquisition. Bipolar SEMG electrodes were made in different electrode diameters Ø 5-30 mm, and the clothing pressure ranged from 6.1 to 12.6 mmHg. The results supported the larger electrodes, and Pc showed better SEMG signal quality by showing lower baseline noise and a gradual increase in the signal to noise ratio (SNR). In particular, electrodes, Ø ≥ 20 mm, and Pc ≥ 10 mmHg showed comparable performance to Ag-Ag/Cl electrodes in current textile-based electrodes. The current study emphasizes and discusses design factors that are particularly required in the designing and manufacturing process of smart clothing with SEMG electrodes, especially as an aspect of clothing design.


Decreased beta-adrenergic stimulation of glycoprotein secretion in CF mice submandibular glands: reversal by the methylxanthine, IBMX.
beta-adrenergic stimulation of glycoprotein secretion was shown to be decreased in submandibular glands of Cystic Fibrosis (CF) mice. The defective response was partially restored by the methylxanthine, IBMX or cpt-cyclic AMP. Cholinergic stimulation of pancreatic amylase secretion was not affected in CF mice, demonstrating that this is not a generalised depression of protein secretion. The data are the first to show that the CF mouse mimics the protein secretion defect in CF human submandibular cells and that the mechanism of correction of the CF defect is via elevation of cyclic AMP. The results are therefore invaluable towards devising a rational pharmaceutical therapy for CF patients.


Treatment of kidney cancer: insights provided by the VHL tumor-suppressor protein.
Germline inactivation of the VHL tumor suppressor gene is associated with an increased risk of clear cell carcinoma of the kidney in the context of von Hippel-Lindau (VHL) disease. Somatic VHL mutations are also common in nonhereditary (sporadic) clear cell carcinomas. The VHL protein (pVHL) has multiple functions that might be linked to tumor suppression, including targeting the hypoxia inducible factor (HIF) transcription factor for polyubiquitylation and proteasomal degradation. HIF, especially HIF2alpha, appears to play a causal role in clear cell renal carcinogenesis based on genotype-phenotype correlations in VHL disease, laboratory experiments with human VHL-/- renal carcinoma cell lines, and genetically engineered mouse models. Deregulation of HIF almost certainly accounts for the high levels of vascular endothelial growth factor (VEGF) observed in kidney cancer and relates to their sensitivity to VEGF inhibitors. In addition, the beneficial effects of mammalian target of rapamycin (mTOR) inhibitors are likely due to, at least partly, their ability to down-regulate HIF. pVHL, in a HIF-independent manner, also regulates a specialized structure called the primary cilium and regulates apoptosis via factors such as NFkappaB. Loss of the primary cilium probably facilitates the development of preneoplastic renal cysts, whereas increased NFkappaB might contribute to the resistance of kidney cancers to conventional cytotoxic agents.


Chronic pulmonary hypertension in sheep: temporal progression of lesions.
Scant data exist on the evolution of the lesions of pulmonary hypertension. This study establishes a model in sheep in which the left upper lobe (LUL) was rendered hypertensive by a systemic-pulmonary shunt while the rest of the pulmonary circulation remained normotensive. By examining lung tissue at 2 months and 1 1/2 years after shunting, we sought the temporal progression of pulmonary hypertensive lesions. In the hypertensive LULs (n = 5), many vascular lesions were seen in contrast to the absence of lesions in both the contralateral normotensive lungs (n = 5) and the "control" lungs from sheep which underwent thoracotomy without shunting (n = 5). Vascular necrosis and vasculitis were present after 2 months (P < 0.01) but disappeared after 1 1/2 years. In contrast, intimal thickening was present after 1 1/2 years (n = 2, P < 0.01) but not significantly after 2 months. These intimal lesions often demonstrated increased cellularity staining positively for factor VIII. Plexiform lesions were present at 2 months (P < 0.05) but were more profuse after 1 1/2 years (P < 0.01). These findings are consistent with an early vascular injury and a later remodeling or reparative process in hemodynamic pulmonary hypertension.


First record of Calotesvindumbarbatus Wagner, Ihlow, Hartmann, Flecks, Schmitz & Böhme, 2021 (Squamata: Agamidae) from China, with revised diagnosis of this species.
Three new species were recently described from the Calotesmystaceus Duméril & Bibron, 1837 complex. Of the three new species, C.vindumbarbatus Wagner, Ihlow, Hartmann, Flecks, Schmitz & Böhme, 2021 was known only from northern Myanmar. Seven specimens of lizard were collected from Tongbiguan Nature Reserve, western Yunnan, China. Phylogenetically, these specimens clustered with the type specimens of Calotesvindumbarbatus from Myanmar with strong support and showed inappreciable genetic divergence from the type specimens of C.vindumbarbatus. We report the first country record of C.vindumbarbatus from China. In addition, a supplementary description, based on the newly-collected specimens and revised diagnosis of this species, was provided.


Human CAAF1 gene--molecular cloning, gene structure, and chromosome mapping.
We have isolated and characterized a cDNA and the gene of the human homologue of CAAF1, a novel member of the S100 calcium-binding protein family. The 276-bp open reading frame encoded a 92-amino acid polypeptide with a predicted molecular mass of 10,575 Da. The deduced amino acid sequence of human CAAF1 showed 66% homology to bovine CAAF1. The human CAAF1 gene consisted of three exons, with the two EF hand motifs of the CAAF1 protein separately encoded by exons 2 and 3. This gene was expressed at a high level in polymorphonuclear leukocytes and at an intermediate level in esophageal mucosa. The tissue distribution of CAAF1 mRNA was different from that of other S100 proteins. Direct R-banding fluorescence in situ hybridization revealed that the human CAAF1 gene was mapped to chromosome 1q21.2-q22, where most of the S100 genes form a cluster.


Right atrial thrombosis as a complication of arrhythmogenic right ventricular cardiomyopathy.
A 65-year-old woman was admitted to our hospital due to palpitation. Electrocardiogram (ECG) showed ventricular tachycardia originating from the right ventricle, and transthoracic echocardiography revealed dilatations of the right atrium and ventricle. The diagnosis of arrhythmogenic right ventricular cardiomyopathy was made. Eleven months later, echocardiography revealed a solid thrombus (36x32 mm) attached to the free wall of the right atrium, and it was surgically resected. Four months after the operation, a solid thrombus (48x30 mm) appeared again at the same site despite anticoagulant treatment. The patient died of both left and right heart failure 33 months after the operation.


[Study of retrieving formaldehyde with differential optical absorption spectroscopy].
The present paper introduces the method of retrieving the concentration of HCHO with differential optical absorption spectroscopy (DOAS). The authors measured ambient HCHO in Beijing region with the help of differential optical absorption spectroscopy instrument made by ourself, and discussed numerous factors in retrieving the concentration of HCHO with differential optical absorption spectroscopy (DOAS), especially, the choice of HCHO wave band, how to avoid absorption of ambient SO2, NO2 and O3, and the influence of the Xenon lamp spectrum structure on the absorption of ambient HCHO. The authors achieved the HCHO concentration by simultaneously retrieving the concentrations of HCHO, SO2, NO2 and O3 with non-linear least square fitting method, avoiding the effect of choosing narrow wave of HCHO and the residual of SO2, NO2, O3 and the Xenon lamp spectrum structure in retrieving process to attain the concentration of HCHO, Finally the authors analyzed the origin of error in retrieving the concentration of HCHO with differential optical absorption spectroscopy (DOAS), and the total error is within 13.7% in this method.


Glycosylation and phosphorylation of lysosomal glycosylasparaginase.
Glycosylasparaginase (EC 188.8.131.52) is a lysosomal amidase which hydrolyzes the bond between asparagine and the sugar moiety in N-linked glycoproteins. Deficiency of the enzyme results in aspartylglycosaminuria (AGU), the most common disorder of glycoprotein degradation. Mature enzyme is formed by two proteolytic cleavage steps subsequent to removal of its signal peptide: (1) an activation cleavage in the ER of the initial single-chain 49-kDa polypeptide into a 27-kDa alpha- and 19-kDa beta-subunit; (2) a cleavage in lysosomes which removes 10 amino acids from the C-terminus of the alpha-subunit without affecting enzyme activity. Each subunit of glycosylasparaginase contains one N-linked oligosaccharide (N38, alpha-subunit; N308, beta-subunit). Both oligosaccharides were phosphorylated and releasable by Endo-H digestion, indicating they were of the high-mannose type. These glycosylation sequenons were mutagenized to determine the role of the oligosaccharide at each site in proper folding and transport of glycosylasparaginase. An N38D mutant underwent the lysosomal processing step, indicating that targeting to lysosomes can be via the phosphorylated beta-subunit oligosaccharide alone. Deletion of the beta-subunit oligosaccharide oat N308 by an aspartic acid substitution resulted in very little protein or enzyme activity in the transfected cells, reemphasizing that glycosylation of the beta-subunit site is important for efficient folding and/or targeting. A different mutation to eliminate the same N-glycosylation sequenon (T310A) yielded more protein and enzyme activity, and a double mutant N38D/T310A yielded the same results as the single beta-subunit substitution. Yield of enzyme for all mutants was increased in cells treated with brefeldin A. The N308 glycosylation site of the beta-subunit appears to be more important in maintaining normal transport and stability of human glycosylasparaginase.


Transcriptional networks in leaf senescence.
Plant senescence is a natural phenomenon known for the appearance of beautiful autumn colors and the ripening of cereals in the field. Senescence is a controlled process that plants utilize to remobilize nutrients from source leaves to developing tissues. While during the past decades, molecular components underlying the onset of senescence have been intensively studied, knowledge remains scarce on the age-dependent mechanisms that control the onset of senescence. Recent advances have uncovered transcriptional networks regulating the competence to senesce. Here, gene regulatory networks acting as internal timing mechanisms for the onset of senescence are highlighted, illustrating that early and late leaf developmental phases are highly connected.


The Combination Analysis Between Bacillus thuringiensis Sip1Ab Protein and Brush Border Membrane Vesicles in Midgut of Colaphellus bowringi Baly.
The secretory insecticidal protein Sip1Ab and crystal protein Cry8Ca from Bacillus thuringiensis (Bt) are widely recognized for their coleopteran insecticidal activities. It is worthwhile to investigate the insecticidal mechanisms of these two proteins against Colaphellus bowringi Baly, which is a serious pest of cruciferous vegetables in China and other Asian countries. To that end, the genes encoding the Sip1Ab and Cry8Ca proteins were amplified from the strain QZL38 genome, then expressed in Escherichia coli, after which bioassays were conducted in C. bowringi larvae. After feeding these two proteins, the histopathological changes in the midguts of C. bowringi larvae were observed using transmission electron microscopy (TEM), and the Brush Border Membrane Vesicle (BBMV) was extracted for competition binding assays. TEM showed that ingestion of Sip1Ab caused a significant reduction in growth of the larvae, disruption of midgut microvilli, and expansion of intercellular spaces. Competition binding assays demonstrated that Sip1Ab bound to C. bowringi BBMV with a high binding affinity. However, a mixture of the two proteins in equal proportions showed no significant difference in insecticidal activity from that of Sip1Ab. These results could provide a molecular basis for the application of Sip1Ab in coleopteran insect control and contribute to the study of the Sip1Ab insecticidal mechanism as well.


Clinical antecedents of neurologic and audiologic abnormalities in survivors of neonatal extracorporeal membrane oxygenation.
Extracorporeal membrane oxygenation is an effective rescue treatment for severe cardiorespiratory failure in term or near term neonates, although cerebral palsy, mental retardation, and sensorineural hearing loss are observed in 10 to 20% of survivors. The objective of the present study was to identify potential risk factors that may explain the neurologic and audiologic sequelae noted in 19% of 181 survivors of neonatal extracorporeal membrane oxygenation from our hospital. Our results suggest the following findings in survivors of severe cardiorespiratory failure treated with neonatal extracorporeal membrane oxygenation: (1) hypotension or the need for cardiopulmonary resuscitation before extracorporeal membrane oxygenation significantly increases the risk of spastic cerebral palsy, (2) profound hypocarbia before extracorporeal membrane oxygenation is associated with a significantly increased risk of hearing loss, (3) mental retardation in the absence of spastic cerebral palsy is unexplained except when due to abnormal fetal brain development, and (4) hypoxemia in the absence of hypotension does not increase the risk of neurologic or audiologic sequelae.


Structure-activity relationship of pamamycins: effects of alkyl substituents.
Nine new pamamycin homologues were isolated from the culture broth of Streptomyces alboniger IFO 12738 using a combination of ODS and NH2 HPLCs, and their structures determined by GC-MS. The structural differences in these homologues are in the numbers and positions of methyl and ethyl groups. The aerial mycelium-inducing and growth-inhibitory activities in S. alboniger of these homologues and their antibiotic activity against Bacillus subtilis were examined. The effects of the alkyl substituents on these activities are discussed.


Effect of outer membrane proteins (OMP) of Shigella on interleukin 2 (IL-2) production by spleen cells of mice.
The kinetics of interleukin (IL-2) release from mouse spleen cells incubated with different doses of outer membrane proteins (OMP) from Shigella was investigated. OMP induced very low activity of IL-2 after 2 and 4 h, and only a slightly higher level of the cytokine was detected after 6 h. However, IL-2 activity increased markedly after 20 and 24 h of incubation, and doses of 5 and 10 micrograms of OMP were found to be the most effective. Spleen cells cultured with OMP for 48 h contained reduced concentration of IL-2.


In vitro reactivation of the FMR1 gene involved in fragile X syndrome.
Fragile X syndrome is the most frequent cause of heritable mental retardation. Most patients have a mutation in the 5' untranslated region of the FMR1 gene, consisting of the amplification of a polymorphic (CGG)nrepeat sequence, and cytogenetically express the folate-sensitive fragile site FRAXA in Xq27.3. Fragile X patients harbour an expanded sequence with >200 CGG repeats (full mutation), accompanied by methylation of most cytosines of the sequence itself and of the upstream CpG island. This abnormal hypermethylation of the promoter suppresses gene transcription, resulting in the absence of the FMR1 protein. Rare individuals of normal intelligence were shown to carry a completely or partially unmethylated full mutation and to express the FMR1 protein. Given this observation and knowing that the open reading frame of the mutated FMR1 gene is intact, we decided to investigate whether its activity could be restored in vitro by inducing DNA demethylation with 5-azadeoxycytidine (5-azadC) in fragile X patients' lymphoblastoid cells. We report that treatment with 5-azadC causes reactivation of fully mutated FMR1 genes with 300-800 repeats, as shown by the restoration of specific mRNA and protein production. This effect correlates with the extent of promoter demethylation, determined by restriction analysis with methylation-sensitive enzymes. These results confirm the critical role of FMR1 promoter hypermethylation in the pathogenesis of the fragile X syndrome, provide an additional explanation for the normal IQ of the rare males with unmethylated full mutations and pave the way to future attempts at pharmacologically restoring mutant FMR1 gene activity in vivo.


Photocontrol of Hook Opening in Cuscuta gronovii Willd.
Hook opening in seedlings of Cuscuta gronovii Willd. occurred only after prolonged exposures to blue, red, or far red light. Prolonged far red exposure was less effective than prolonged exposure to red or blue light. Brief far red irradiation inhibited the inductive effect of red light. The far red inhibition was in turn reversed by brief red irradiation. These effects suggest the involvement of two photosystems in the control of hook opening in Cuscuta gronovii Willd.: a phytochrome-mediated system and a separate high energy requirement.


Wet-chemical approaches to porous nanowires with linear, spiral, and meshy topologies.
We report universal approaches for porous nanowires (NWs), and porous NWs with spiral and meshy topologies that have been developed via anodic aluminum oxide (AAO) confined wet-chemical synthesis. Materials such as CuOx, Pd, and Cu NWs are taken as examples for porous NWs and porous NWs with spiral and meshy topologies. Immediate benefits are demonstrated in hydrogen sensors as examples. We observed that hydrogen concentrations as low as 0.2% (v/v) were detected, that critical temperatures of the reverse sensing behavior as low as 239.9 K were measured and that better baseline-stability was confirmed compared with those fabricated with pure Pd NWs. Our approaches are anticipated to work on the synthesis of the porous NWs of other materials that could be obtained via wet-chemistry with potential as candidates for the next generation nanodevices (e.g., gas sensors) and other applications (e.g., catalysts).


Cholecystoduodenal fistula presenting with upper gastrointestinal bleeding: A case report.
Cholecystoduodenal fistula is a rare complication of cholelithiasis. Symptoms are usually non-specific and often indistinguishable from those of etiologic diseases, but it rarely presents as severe gastrointestinal bleeding. Bleeding associated with cholecystoduodenal fistula usually requires surgery because significant bleeding from the cystic artery is unlikely to be resolved by conservative management or endoscopic hemostasis. We report a case of cholecystoduodenal fistula that presented with hematemesis which was diagnosed by endoscopy and computed tomography. Endoscopic hemostasis could not be achieved, but surgical treatment was successful. Additionally, we have presented a literature review. Cholecystoduodenal fistula should be considered as differential diagnosis when a patient with history of gallstone disease presents with gastrointestinal bleeding.


Human apolipoprotein B gene intestinal control region.
Recently, we reported that a 315 bp enhancer, located over 55 kilobases (kb) upstream of the transcriptional start site of the human apolipoprotein B (apoB) gene, was sufficient to direct high-level expression of human apoB transgenes in mice. In this report, we expand our analysis of the distant apoB intestinal control region (ICR), by examining the function of segments in the vicinity of the 315 bp intestinal enhancer (315 IE). DNaseI hypersensitivity (DH) studies of a 4.8 kb segment from the ICR revealed three new DH sites, in addition to the previously described DH1 region present within the 315 IE. DH2 mapped to a 485 bp segment (485 IE) immediately upstream of the 315 IE that exhibited strong intestinal enhancer activity in transient transfection experiments with intestine-derived CaCo-2 cells. Within the DH2 region, an HNF-4/ARP-1 binding site was demonstrated by gel retardation experiments. A 1.8 kb segment incorporating the 485 IE was capable of driving expression of human apoB transgenes in the intestines of mice. Additionally, a third component of the apoB ICR was found about 1.2 kb downstream of the 315 IE, within a 1031 bp segment (1031 IE) that also harbored two DH sites, DH3 and DH4. This segment did not display enhancer activity but was capable of driving transgene expression in the intestine. The three components of the ICR displayed a similar pattern of apoB mRNA expression along the horizontal axis of the intestine. The previously characterized in vivo liver-specific elements of the apoB gene, namely, the second intron enhancer and the 5' upstream liver enhancer, did not play a role in intestinal expression of apoB transgenes in mice.


[The ProSeal-LM, a new variant of the laryngeal mask: description and first clinical results].
The ProSeal-LMA is a modification of the laryngeal mask airway (LMA) invented by AIJ Brain. It differs from the known models in three major respects: An additional lumen extending into the tip of the cuff allows insertion of a gastric tube. A pocket immediately behind the cuff accommodates a finger or a siliconated metal introducer and thus facilitates insertion. An additional cuff at the dorsal aspect of the mask pushes the mask into a ventral direction and thus improves the seal around the glottic opening. Our experience after 8 months of clinical use and first data from an international multi-center-study (24 ProSeal-LMA/24 Standard-LMA) are reported. With a ProSeal-LMA insertion of a gastric tube is much easier and more reliable than with a Standard-LMA (24/24 patients vs. 2/24 patients). Judged from visibility of the oesophagus during fibre-endoscopy the position of the ProSeal-LMA is superior to that of the Standard-LMA. Both are equally well tolerated and handled. Most remarkable is a better seal for the ProSeal-LMA (pressure for a leak of 3 L/min: 31 mbar compared to 20 mbar (mean) for the Standard-LMA). Therefore the ProSeal-LMA seems suitable for anaesthesia procedures with IPPV, which up to now are a domain of endotracheal intubation.


Sulfide remediation by pulsed injection of nitrate into a low temperature Canadian heavy oil reservoir.
Sulfide formation by oil field sulfate-reducing bacteria (SRB) can be diminished by the injection of nitrate, stimulating the growth of nitrate-reducing bacteria (NRB). We monitored the field-wide injection of nitrate into a low temperature (approximately 30 degrees C) oil reservoir in western Canada by determining aqueous concentrations of sulfide, sulfate, nitrate, and nitrite, as well as the activities of NRB in water samples from 3 water plants, 2 injection wells, and 15 production wells over 2 years. The injection water had a low sulfate concentration (approximately 1 mM). Nitrate (2.4 mM, 150 ppm) was added at the water plants. Its subsequent distribution to the injection wells gave losses of 5-15% in the pipeline system, indicating that most was injected. Continuous nitrate injection lowered the total aqueous sulfide output of the production wells by 70% in the first five weeks, followed by recovery. Batchwise treatment of a limited section of the reservoir with high nitrate eliminated sulfide from one production well with nitrate breakthrough. Subsequent, field-wide treatment with week-long pulses of 14 mM nitrate gave breakthrough at an additional production well. However, this trend was reversed when injection with a constant dose of 2.4 mM (150 ppm) was resumed. The results are explained by assuming growth of SRB near the injection wellbore due to sulfate limitation. Injection of a constant nitrate dose inhibits these SRB initially. However, because of the constant, low temperature of the reservoir, SRB eventually grow back in a zone further removed from the injection wellbore. The resulting zonation (NRB closest to and SRB further away from the injection wellbore) can be broken by batch-wise increases in the concentration of injected nitrate, allowing it to re-enter the SRB-dominated zone.


Frontal plane knee moments in golf: effect of target side foot position at address.
Golf has the potential to keep people active well into their later years. Injuries to the target side knee have been reported in golfers, yet no mechanisms for these injuries have been proposed. The loads on the knee during the golf swing may be insufficient to cause acute injury, yet they may be a factor in the progression of overuse/degenerative conditions; therefore, research developing swing modifications that may alter loading of the knee is warranted. It has been suggested that the proper golf set-up position has the target-side foot externally rotated but no reasoning for this modification has been provided. Frontal plane knee moments have been implicated in many knee pathologies. Therefore, this study used a 3-dimensional link segment model to quantify the frontal plane knee moments during the golf swing in a straight (STR) and externally rotated (EXT) target-side foot position. Subjects were 7 collegiate golfers and knee moments were compared between conditions using repeated measures T-tests. The golf swing knee moment magnitudes were also descriptively compared to those reported for two athletic maneuvers (drop jump landing, side-step cutting) and activities of daily living (gait, stair ascent). The EXT condition decreased the peak knee adduction moment as compared to the STR condition; however, foot position had no effect on the peak knee abduction moment. Also, the magnitude of the knee adduction moments during the two activities of daily living were 9-33% smaller than those experienced during the two different golfing conditions. The drop jump landing and golf swing knee moments were of similar magnitude (STR= - 5%, EXT= + 8%); however, the moments associated with side- step cutting were 50-71% larger than those on the target side knee during the golf swing. The loading of the target side knee during the golf swing may be a factor in the development and progression of knee pathologies and further research should examine ways of attenuating these loads through exercise and swing modifications. Key pointsAn externally rotated front foot position at address would be recommended for those with medial knee pathology in the target side limb.There is a large valgus moment on the target side knee during the golf swing that is not decreased with external rotation of the foot at address.The potential of the knee moments on the target side limb to lead to knee pathologies in golfers needs to be further investigated.


Sagittal osteotomy of the patella after Morscher.
The aim of this study was to present long-term results of sagittal osteotomy of the patella after Morscher. The study included 70 patients treated for patellar dysplasia with a postoperative follow-up from nine to 20 years. There were 59 females and 11 males with an average age of 21 years at the time of operation. Results were evaluated for the entire group of 70 patients and then presented separately for the 30 patients in whom sagittal osteotomy of the patella was performed as a single procedure and 40 patients in whom, in addition to sagittal osteotomy of the patella, medialisation and ventralisation or distalisation of the tibial tuberosity were also performed. The mean value of the Wiberg patellar angle was 112 degrees preoperatively and 140 degrees postoperatively. In the whole group of patients excellent results were obtained in 24 (35%), good results in 30 (42%), fair results in 13 (19%) and poor results in three (4%) patients. In 30 patients with sagittal osteotomy as a single operation excellent results were obtained in 13 (43%), good results in 14 (47%) and fair results in three (10%) patients, while in the 40 patients with sagittal osteotomy and additional surgical procedures, 11 (27%) were excellent, 16 (40%) good, ten (25%) fair and three (8%) had poor results. Sagittal osteotomy of the patella after Morscher is an enrichment of the spectrum of the secondary-causal and preventive procedures for the treatment of patello-femoral disorders.


Influences of task and attention on action verb congruence effects: How automatic are embodiment effects?
Three experiments investigated changes in the sizes of Stroop-like congruency effects of hand- and foot-related action verbs on the latencies of hand and foot motor responses. Congruency effects were present in all experiments, with faster responses for a verb associated with the responding limb than for a verb associated with the opposite limb (e.g., faster foot than hand responses in the presence of the verb "kick"). As compared with a task in which the verbs were completely irrelevant, this congruency effect was greatly increased when participants had to make lexical decisions about the verbs, and the effect was also increased-although to a lesser extent-when participants had to make physical (i.e., size) judgments about them. In some cases, the congruence effect was also larger when the hand/foot discrimination response was determined by a reading task than by a color discrimination task. We conclude that the Stroop-like congruence effects of action verbs do not result from fully automatic processing but instead depend on at least the duration and linguistic nature of verb processing.


Cerebrovascular pathology and dementia in autopsied Honolulu-Asia Aging Study participants.
Clinicopathologic data from 285 autopsies were analyzed. The decedents were long-standing participants in the Honolulu-Asia Aging Study, a prospective epidemiologic investigation of stroke, neurodegenerative diseases, and aging. We assessed the prevalence at death of four primary neuropathologic processes using specific microscopic lesions as indicators. An algorithm was developed to assign each decedent to one of six subsets, corresponding to pathologic dominance by microvascular lesions (14% of decedents), Alzheimer lesions (12%), hippocampal sclerosis (5%), cortical Lewy bodies (5%), codominance by two or more primary processes (9%), or without a dominant pathologic process recognized (55%). Definite or probable dementia had been identified in 118 of the decedents. The proportions of men in each subset identified as demented were (in the same order) 57%, 53%, 79%, 57%, 76%, and 25%. In this autopsied panel of older Japanese-American men, the importance of microvascular lesions as a likely explanation for dementia was nearly equal to that of Alzheimer lesions. The cerebrovascular lesion type most essentially and inclusively related to dementia was multiple microinfarction.


Rheolytic thrombectomy in acute myocardial infarction: the Florence experience and objectives of the multicenter randomized JETSTENT trial.
The Florence-AngioJet randomized trial was the first study that assessed the efficacy of Rheolytic thrombectomy before direct infarct artery stent implantation in patients who underwent percutaneous coronary intervention (PCI) for acute myocardial infarction (MI). This study was based on a sample of 100 patients with a first acute MI and the endpoints of the study were early ST-segment resolution, corrected thrombolysis in myocardial infarction (TIMI) frame count, and infarct size as assessed by technetium-99m sestamibi scintigraphy at 1 month. All 3 endpoints were reached. Patients randomized to thrombectomy before direct stenting had a higher incidence of early ST-segment elevation resolution (90% vs. 72%, p = 0.022), lower corrected TIMI frame counts (18.2 +/- 7.7 vs. 22.5 +/- 11.0, p = 0.032), and smaller infarcts (13.0 +/- 11.6% vs. 21.2 +/- 18.0%, p = 0.010) as compared to patients randomized to direct stenting alone. The AngioJET Thrombectomy and STENTing for Treatment of Acute Myocardial Infarction (JETSTENT) trial is a multi-center international randomized trial based on a sample of 500 patients with acute MI, the aim of which is the confirmation of the results of the Florence trial. Patients with a history of previous MI will be enrolled. No restriction based on clinical status on presentation or high-risk coronary anatomy will be used. Thus, patients with cardiogenic shock will be included. To be eligible, patients must have visible thrombus or a persisting total occlusion, and all use of AngioJet must follow the specific technique used in the Florence experience. The primary hypothesis of the study is that rheolytic thrombectomy before infarct artery stenting provides a better reperfusion as revealed by electrocardiogram and scintigraphy. The subsequent increase in myocardial salvage could result in a decreased incidence of death and heart congestive failure due to left ventricle remodeling at a mid-term follow up.


Clinical experience with autofluorescence imaging system in patients with lung cancers and precancerous lesions.
It is important to detect preinvasive bronchial lesions before they become invasive cancer, because detection of early cancer is expected to lead to a cure. Autofluorescence bronchoscopy is a useful device in the detection of preinvasive and cancerous lesions. Recently, a new autofluorescence bronchoscopic system, autofluorescence imaging (AFI) system, has been developed. We evaluated the efficacy of AFI in the diagnosis of precancerous and cancerous lesions. A total of 31 patients underwent both conventional white-light bronchoscopy (WLB) and AFI from January 2002 to September 2004. We evaluated autofluorescence findings using a four-point scale: AFI-I, II, III, and B. The findings in WLB were evaluated on a three-point scale: WLB-I, II, and III. Abnormal areas by WLB and AFI were biopsied for histopathological examinations. A total of 64 lesions were evaluated. When the AFI-III finding was regarded as positive in AFI and WLB-III as positive in WLB, sensitivity for severe dysplasia or worse was 94.7% with AFI and 73.7% with WLB, respectively. AFI is an effective system for the detection of precancerous and cancerous lesions.


[State of the art: treatment of malignant pleural and pericardial effusions].
Symptomatic malignant pleural effusions should be treated systemic chemotherapy in chemo-sensitive tumors such as small cell lung cancer, breast cancer, lymphoma, or ovarian cancer. In other non-chemo-sensitive malignancies including non-small cell lung cancer, water-sealed tube drainage and pleurodesis is the standard treatment of choice in most of the cases. Drugs for instillation should be blomycin or OK-432 if commercially available. Instead of the former standard drug tetracycline, doxycycline has been frequently used. As we have no randomized trials, this drug awaits phase III trials. Talc slurry has been accepted and counted as one of the standard choices in the western countries, however, it usually needs general anesthesia and adverse effects are not negligible. As we have little experience on this modality, it should not be considered as a standard treatment. Other antitumor drugs instillation, thoraco-abdominal shunting, and pleuro-pneumonectomy should be considered experimental because of the lack of randomized trials. Symptomatic pericardial malignant effusion or cardiac tamponade is an oncologic emergency. We had better to treat the patient immediately by pericardiocentesis under the cardiac echographic guidance. It should be reserved to solve in randomized trials that the best method would be pericardiocentesis alone, percutaneous continuous drainage, pericardial fenestration, or pericardio-thoraco fenestration. Instillation of drug like doxycycline, OK-432, or bleomycin, lacks phase III comparison and it should be categorized as experimental.


Reactive Aggression Affects Response Inhibition to Angry Expressions in Adolescents: An Event-Related Potential Study Using the Emotional Go/No-Go Paradigm.
Although it is well established that response inhibition to angry expressions is impaired among reactively aggressive adolescents, the cognitive processes underlying this effect remain unclear. The main goal of our study was to investigate the time course of response inhibition to angry expressions in reactively aggressive adolescents compared to controls. In total, 23 reactively aggressive adolescents and 23 control adolescents were recruited to participate in an event-related potential (ERP) study measuring response inhibition to angry expressions with an emotional Go/No-go paradigm. The results showed that when presented angry or happy expressions, reactively aggressive adolescents showed a smaller No-go P3 effect than the control group. These results indicate that response inhibition to angry expressions in reactively aggressive adolescents is impaired at the later stage of the actual inhibitory control. The characteristics of response inhibition to happy expressions in reactively aggressive adolescents are similar to those in response to angry expressions.


Postarthroscopic glenohumeral chondrolysis of the shoulder.
Postarthroscopic glenohumeral chondrolysis is a devastating, poorly understood, and relatively rare complication. True chondrolysis involves the dissolution of articular cartilage, including the matrix and cellular elements, leading to premature and irreversible articular cartilage loss. Several factors have been implicated in this phenomenon; however, to date, no study has conclusively ascertained the causation. Potential causative agents include subclinical infection, high volume intra-articular infusion of certain anesthetics, arthroscopic implants, suture material, and thermal energy. One must also consider the possibility that chondrolysis represents an ongoing immunogenic process interrupted or possibly potentiated by surgical intervention. The complex homeostasis of articular cartilage is undoubtedly sensitive to agents introduced into the joint including mechanical, chemical, and temperature-dependent interventions. To date, several papers have described the phenomenon and the potential associations; however, there is no definitive answer although the use of high-dose bupivacaine as an intra-articular anesthetic seems to be contraindicated. The purpose of this article is to review the basic science regarding chondrolysis and to assess the current literature which focuses on postarthroscopic glenohumeral chondrolysis, as well as innovative treatment alternatives. It is unlikely that postoperative chondrolysis will be clearly understood until controlled studies are available, of which there are currently none.


External validation of a prognostic model for predicting survival of cirrhotic patients with refractory ascites.
Cirrhotic patients with refractory ascites (RA) have a poor prognosis, although individual survival varies greatly. A model that could predict survival for patients with RA would be helpful in planning treatment. Moreover, in cases of potential liver transplantation, a model of these characteristics would provide the bases for establishing priorities of organ allocation and the selection of patients for a living donor graft. Recently, we developed a model to predict survival of patients with RA. The aim of this study was to establish its generalizability for predicting the survival of patients with RA. The model was validated by assessing its performance in an external cohort of patients with RA included in a multicenter, randomized, controlled trial that compared large-volume paracentesis and peritoneovenous shunt. The values for actual and model-predicted survival of three risk groups of patients, established according to the model, were compared graphically and by means of the one-sample log-rank test. The model provided a very good fit to the survival data of the three risk groups in the validation cohort. We also found good agreement between the survival predicted from the model and the observed survival when patients treated with peritoneovenous shunt and with paracentesis were considered separately. Our survival model can be used to predict the survival of patients with RA and may be a useful tool in clinical decision making, especially in deciding priority for liver transplantation.


[Hyperalgesia induced by intrathecal administration of nitroglycerin involves NMDA receptor activation in the spinal cord].
Spinal NMDA receptors are involved in hyperalgesia and chronic pain. The activation of spinal NMDA receptor results in the production of nitric oxide in the second order neurons in the spinal cord dorsal horn. We investigated the effects of intrathecally administered nitroglycerin (NTG) which releases nitric oxide in the cell. Formalin test which reflects phasic and tonic nociception was used as a nociceptive measure in rats with chronically implanted intrathecal catheters. Intrathecal injection of NTG resulted in the increase of flinching behavior induced by formalin injection to one paw in phase 1 (phasic) and phase 2 (tonic) responses in a dose-dependent manner. Intrathecally administered NMDA antagonist, MK-801 (MK) dose-dependently inhibited the effect of NTG but the effect was significant only in the phase 2 of the formalin test. MK given after formalin injection had significantly less effect on the phase 2 response. L-NAME (NOS inhibitor), MB (guanylate cyclase inhibitor) and HB (nitric oxide scavenger) significantly antagonized the hyperalgesic effect of NTG in the phase 2 of the formalin test. These results show that nitric oxide plays an important role in producing hyperalgesia in the spinal cord acting postsynaptically as well as pre-synaptically.


Cervical and mediastinal abscess as a manifestation of histoplasmosis.
Histoplasmosis is the most common endemic respiratory mycosis in the United States. Disseminated histoplasmosis generally is initially seen with systemic or respiratory complaints. Presentation of histoplasmosis as a neck mass is rare. Due to this unusual presentation and the diagnostic implications, we present a case of disseminated histoplasmosis that presented as a neck abscess. Unusual presentations of histoplasmosis may occur even in patients who are not immunocompromised. The diagnosis and management of histoplasmosis is reviewed. Histoplasmosis should be considered in the workup of a cervical abscess even in the immunocompetent host.


Pharmacokinetics of moxalactam in patients with renal insufficiency.
Moxalactam pharmacokinetics were determined in 18 patients with renal insufficiency (creatinine clearance, 0 to 99 ml/min). Each patient was given 0.5 g of moxalactam intramuscularly. Drug half-life ranged from 4.1 to 49.1 h and correlated inversely with creatinine clearance (r = -0.97). Total body drug clearance ranged from 0 to 88 ml/min, and renal clearance ranged from 0 to 57 ml/min. In four patients studied during hemodialysis, drug half-life was 21.7 +/- 7.5 h (mean +/- standard error) between dialyses and 4.4 +/- 0.5 h during dialysis. Moxalactam dialysance averaged 44 +/- 2 ml/min per m2 of dialyzer surface area, and approximately 50% of the drug was removed during a single hemodialysis. We confirmed that moxalactam is eliminated from the body primarily by renal excretion. Recommendations are given for dosage adjustment in patients with renal insufficiency.


Recent Chemical Approaches for Site-Specific Conjugation of Native Antibodies: Technologies toward Next-Generation Antibody-Drug Conjugates.
Antibody-drug conjugates (ADCs), which consist of three components, antibody, linker, and payload, can function as "magic bullets". These conjugates offer the ability to target drug delivery to specific cells, based on cell-specific recognition and the binding of an antigen by a monoclonal antibody (mAb). In particular, by delivering a cytotoxic payload to cancer cells, ADCs are expected to provide a breakthrough in oncology treatments by providing a way to increase efficacy and decrease toxicity, in comparison with traditional chemotherapeutic treatments. The development of ADC therapeutics has dramatically progressed in the past decade and two ADCs have been approved and used as anticancer drugs in the clinic. However, several critical issues regarding the performance of ADCs are still being discussed and investigated. Indeed, in the past few years, several groups have reported that, changing the number and position of the drug payloads in the ADCs, affects the pharmacokinetics, drug release rates, and biological activity. The use of conventional heterogeneous conjugation methods for ADC preparation results in the drug/antibody ratio and connecting position of the payload having stochastic distributions. Therefore, it is important to investigate how these potential problems can be circumvented through site-specific conjugation. Herein, various site-specific chemical conjugation strategies with native mAbs that are currently used for the production of ADCs, including residue-selective labeling for generating ADCs, disulfide rebridging, and affinity-peptide-mediated site-specific chemical conjugation technologies, are reviewed and described.


Predisposition to mouse thymic lymphomas in response to ionizing radiation depends on variant alleles encoding metal-responsive transcription factor-1 (Mtf-1).
Genetic predisposition to cancers is significant to public health because a high proportion of cancers probably arise in a susceptible human subpopulation. Using a mouse model of gamma-ray-induced thymic lymphomas, we performed linkage analysis and haplotype mapping that suggested Mtf-1, metal-responsive transcription factor-1 (Mtf-1), as a candidate lymphoma susceptibility gene. Sequence analysis revealed a polymorphism of Mtf-1 that alters the corresponding amino acid at position 424 in the proline-rich domain from a serine in susceptibility strains to proline in resistant strains. The transcriptional activity of Mtf-1 encoding serine and proline was compared by transfecting the DNA to Mtf-1-null cells, and the change to proline conferred a higher metal responsiveness in transfections. Furthermore, the resistant congenic strains possessing the Mtf-1 allele of proline type exhibited higher radiation inducibility of target genes than susceptible background strains having the Mtf-1 allele of serine type. Since products of the targets such as metallothionein are able to suppress cellular stresses generated by irradiation, these results suggest that highly inducible strains having Mtf-1 of proline type are refractory to radiation effects and hence are resistant to lymphoma development.


Chemomechanical regulation of SNARE proteins studied with molecular dynamics simulations.
SNAP-25B is a neuronal protein required for neurotransmitter (NT) release and is the target of Botulinum Toxins A and E. It has two SNARE domains that form a four-helix bundle when combined with syntaxin 1A and synaptobrevin. Formation of the three-protein complex requires both SNARE domains of SNAP-25B to align parallel, stretching out a central linker. The N-terminal of the linker has four cysteines within eight amino acids. Palmitoylation of these cysteines helps target SNAP-25B to the membrane; however, these cysteines are also an obvious target for oxidation, which has been shown to decrease SNARE complex formation and NT secretion. Because the linker is only slightly longer than the SNARE complex, formation of a disulfide bond between two cysteines might shorten it sufficiently to reduce secretion by limiting complex formation. To test this idea, we have carried out molecular dynamics simulations of the SNARE complex in the oxidized and reduced states. Indeed, marked conformational differences and a reduction of helical content in SNAP-25B upon oxidation are seen. Further differences are found for hydrophobic interactions at three locations, crucial for the helix-helix association. Removal of the linker induced different conformational changes than oxidation. The simulations suggest that oxidation of the cysteines leads to a dysfunctional SNARE complex, thus downregulating NT release during oxidative stress.


Risk of chronic obstructive pulmonary disease. Collaborative assessment of the validity of the Tecumseh index of risk.
Predictors of chronic obstructive pulmonary disease (COPD) have been identified in the prospective epidemiologic study of the population of Tecumseh, Michigan. Risk of developing COPD within 10 yr can be estimated from a profile that includes as risk factors age, sex, cigarette smoking habits, and forced expiratory volume in one second (FEV1). The index of risk placed 63% of male incidence cases and 64% of female incidence cases in the top 10% of the risk distribution and 81% of male and 86% of female COPD cases in the top 20% of the risk distribution for Tecumseh. The validity of the Tecumseh index of risk for other populations was determined in a collaborative investigation of data collected in longitudinal epidemiologic studies in Baltimore, Boston, Framingham, Louisiana, Staveley, and Tucson. The extent to which the risk model fitted these data sets was assessed by comparing predicted (or expected) onsets of COPD in each population with observations made in each study. The predictors of COPD identified in Tecumseh were shown to be the most important risk factors in the other populations as well. The goodness-of-fit of the index was satisfactory overall. In all populations, a high risk score was associated with an increased incidence of COPD, thus confirming the predictive ability of the risk index. The Tecumseh index of risk provides a practical method for developing a risk profile from answers to standard questions and simple tests of lung function. Risks are greatest for heavy cigarette smokers with reduced lung function, lower in smokers who stop smoking or reduce their cigarette consumption, and lowest of all in nonsmokers with above average lung function.(ABSTRACT TRUNCATED AT 250 WORDS)


Reduction of interstitial cells of Cajal in esophageal atresia.
Postrepair esophageal dysmotility and gastroesophageal reflux are well-known consequences in patients with congenital esophageal atresia (EA) with or without distal tracheoesophageal fistula (TEF). The interstitial cells of Cajal (ICC), considered the intestinal pacemaker, are altered in congenital diseases with abnormal peristalsis, but no data are available for EA. Therefore, presence and maturation of ICC was verified in EA-TEF newborns. Fifteen full-term neonates underwent repair of EA-TEF. Control specimens were from 10 newborns who died of nonesophageal diseases. Specimens from upper pouch, fistula, proximal, and distal esophagus were processed for hematoxylin and eosin, c-kit immunohistochemistry for ICC identification, and transmission electron microscopy. Frequency of c-kit-positive cells was evaluated in 20 fields per slide using a visual score (absent, very low, low, medium, high, very high). Morphocytometry and statistical analysis were also performed. In the proximal normal esophagus, ICC frequency was very high (3 cases), high (5), and medium (2); distally, it was high (4) and medium (6). In EA-TEF upper pouch, it was high (2) and medium (13); in the fistula, it was medium (5), low (6), very low (3), and absent (1). Morphocytometry confirmed these results. Comparison between pouch and fistula versus proximal and lower esophagus, respectively, showed statistically significant differences. Transmission electron microscopy demonstrated ICC immaturity in EA-TEF. The significant lower ICC density in EA-TEF is in favor for the pathogenesis of esophageal dysmotility frequently observed in such patients.


[Physical examination and palpation findings of mammary glands and indications of udder health in goat milk].
In dairy goats there is less evidence for relationships between udder form traits, results of physical udder examinations and mastitis indicators in the milk than in dairy cows. In 413 goats (predominantly Weisse Deutsche Edelziege and Bunte Deutsche Edelziege) from five herds (free from C.A.E.) repeated investigations of 2537 udder halves and fore milk samples were carried out in order to compare udder traits with findings in the milk. Less than 20% positive bacteriological findings and a low incidence of clinical mastitis testified a good clinical udder health status of the herds. Small teat-floor distances, loose hanging of the udders and bottle-shaped teats, findings which tended to become more frequent as lactation and lactation numbers progressed, indurative alterations of the mammary tissues and the teats tended to be connected with higher milk cell counts (> 1 million/microliter), more polymorphonuclear milk cells (> 40%), higher electrical milk conductivity (> 6.8 mS/cm) and lower milk lactose content (< 4.6%). A similar effect had a bad state of foot trimming. It is proposed to include the studied udder traits into herd health programs and breeding schemes for goats.


A 2021 Update on Syphilis: Taking Stock from Pathogenesis to Vaccines.
In 2021 the scientific community's efforts have been focused on solving the back-breaking challenge of the COVID-19 pandemic, but sexually transmitted infections (STI) are still one of the most common global health problems. Syphilis is a systemic disease caused by the spirochaete Treponema pallidum (TP) and is one of the oldest known diseases. Its incidence has increased in the last few years and syphilis still remains a contemporary plague that continues to afflict millions of people worldwide. Despite research improvements, syphilis pathogenesis is not completely clear; clinical presentation is very heterogeneous and the diagnosis can sometimes be difficult. Furthermore, few therapeutic options are available, and a vaccine has not been found yet. In this review, we describe the most recent evidence concerning the clinical manifestation, diagnosis, treatment and vaccine prospectives for this disease.


New Perspectives in Liver Transplantation: From Regeneration to Bioengineering.
Advanced liver diseases have very high morbidity and mortality due to associated complications, and liver transplantation represents the only current therapeutic option. However, due to worldwide donor shortages, new alternative approaches are mandatory for such patients. Regenerative medicine could be the more appropriate answer to this need. Advances in knowledge of physiology of liver regeneration, stem cells, and 3D scaffolds for tissue engineering have accelerated the race towards efficient therapies for liver failure. In this review, we propose an update on liver regeneration, cell-based regenerative medicine and bioengineering alternatives to liver transplantation.


Introducing the Microbiome into Precision Medicine.
Understanding how individual people respond to medical therapy is a key facet of improving the odds ratio that interventions will have a positive impact. Reducing the non-responder rate for an intervention or reducing complications associated with a particular treatment or surgery is the next stage of medical advance. The Precision Medicine Initiative, launched in January 2015, set the stage for enhanced collaboration between researchers and medical professionals to develop next-generation techniques to aid patient treatment and recovery, and increased the opportunities for impactful pre-emptive care. The microbiome plays a crucial role in health and disease, as it influences endocrinology, physiology, and even neurology, altering the outcome of many different disease states, and it augments drug responses and tolerance. We review the implications of the microbiome on precision health initiatives and highlight excellent examples, whereby precision microbiome health has been implemented.


Overexpression of microRNA gga-miR-1650 decreases the replication of avian leukosis virus subgroup J in infected cells.
MicroRNAs (miRNAs) are a class of small regulatory non-coding RNAs that modulate gene expression at the post-transcriptional level, playing a crucial role in cell differentiation and development. Recently, some reports have demonstrated that a number of cellular miRNAs play a role during viral infection. In this study, a luciferase-reporter system carrying the 5' untranslated region (5' UTR) and 3' UTR of avian leukosis virus subgroup J (ALV-J) was used to determine whether cellular miRNAs are involved in ALV-J infection. The miRNA gga-miR-1650 was screened for its potential interaction with the 5' UTR of ALV-J and the ability to suppress luciferase-reporter activity. A mutational analysis of predicted gga-miR-1650-binding sites showed that the 5' and 3' ends of gga-miR-1650 contributed to the interaction between gga-miR-1650 and its target located at the 5' UTR. Overexpression of miRNA gga-miR-1650 was shown to downregulate the expression of the Gag protein and influence the replication of ALV-J through binding to the 5' UTR. Overall, this report provides the basis for the development of new strategies for anti-ALV-J intervention.


Stem Cell Based Models in Congenital Hyperinsulinism - Perspective on Practicalities and Possibilities.
Congenital hyperinsulinism (CHI) is a severe inherited neonatal disorder characterized by inappropriate insulin secretion caused by genetic defects of the pancreatic beta cells. Several open questions remain in CHI research, such as the optimal treatment for the most common type of CHI, caused by mutations in the genes encoding ATP-sensitive potassium channels, and the molecular mechanisms of newly identified CHI genes. Answering these questions requires robust preclinical models, particularly since primary patient material is extremely scarce and accurate animal models are not available. In this short review, we explain why pluripotent stem cell derived islets present an attractive solution to these issues and outline the current progress in stem-cell based modeling of CHI. Stem cell derived islets enable the study of molecular mechanisms of CHI and the discovery of novel antihypoglycemic drugs, while also providing a valuable model to study the biology of variable functional states of beta cells.


Evolution of network biomarkers from early to late stage bladder cancer samples.
We use a systems biology approach to construct protein-protein interaction networks (PPINs) for early and late stage bladder cancer. By comparing the networks of these two stages, we find that both networks showed very significantly different mechanisms. To obtain the differential network structures between cancer and noncancer PPINs, we constructed cancer PPIN and noncancer PPIN network structures for the two bladder cancer stages using microarray data from cancer cells and their adjacent noncancer cells, respectively. With their carcinogenesis relevance values (CRVs), we identified 152 and 50 significant proteins and their PPI networks (network markers) for early and late stage bladder cancer by statistical assessment. To investigate the evolution of network biomarkers in the carcinogenesis process, primary pathway analysis showed that the significant pathways of early stage bladder cancer are related to ordinary cancer mechanisms, while the ribosome pathway and spliceosome pathway are most important for late stage bladder cancer. Their only intersection is the ubiquitin mediated proteolysis pathway in the whole stage of bladder cancer. The evolution of network biomarkers from early to late stage can reveal the carcinogenesis of bladder cancer. The findings in this study are new clues specific to this study and give us a direction for targeted cancer therapy, and it should be validated in vivo or in vitro in the future.


Hepatobiliary and Pancreatic neoplasms in patients with McCune-Albright syndrome.
McCune-Albright syndrome (MAS), which includes polycystic fibrous dysplasia, precocious puberty, and café au lait spots, is a rare disorder caused by somatic activating mutations of the GNAS gene. GNAS mutations have also been implicated in various sporadic tumors, including hepatobiliary and pancreatic neoplasms. The aim of this study was to assess the prevalence of hepatobiliary and pancreatic neoplasms in patients with McCune-Albright syndrome. Nineteen patients diagnosed between 1995 and 2012 with MAS in a tertiary referral center for rare growth disorders were screened with dedicated gadolinium-enhanced magnetic resonance imaging for hepatobiliary and pancreatic neoplasms between June 2011 and December 2012. Six (32%) of the 19 screened patients were found to have hepatic, pancreatic, or biliary lesions, excluding liver hemangiomas, liver cysts, and focal nodular hyperplasia. This includes pancreatic ductal lesions observed in 4 patients, including numerous branch-duct intraductal papillary mucinous neoplasms in 3 patients. Biliary lesions were observed in 1 patient, with a large choledochal cyst also involving the left biliary branch. Finally, multiple inflammatory/telangiectatic hepatic adenomas were observed in 2 patients, including 1 with proven somatic GNAS mutation. We describe the first observation of syndromic intraductal papillary mucinous neoplasms and the new association between MAS and pancreatic neoplasms, namely intraductal papillary mucinous neoplasms of the pancreas but also rare hepatobiliary neoplasms including liver adenomas and choledochal cysts. These findings strongly suggest that somatic activating GNAS mutations, possibly through cAMP pathway disorders, are involved in the tumorigenesis of hepatobiliary and pancreatic tissues originating from the foregut endoderm and have led us to use a routine screening by dedicated magnetic resonance imaging including both pancreatobiliary and liver sequences in patients with MAS.


Acute toxicity of veterinary and agricultural formulations of organophosphates dichlorvos and diazinon in chicks.
Formulation components of organophosphate insecticidal preparations might affect their toxic action in animals. The objective of this study was to examine and compare the acute toxicity and cholinesterase inhibition in seven to 14-day-old chicks dosed orally with dichlorvos and diazinon in standard veterinary and agricultural formulations. The acute (24 h) oral median lethal doses (LD50) of the formulations were determined using the up-and-down method. Respective LD50 of dichlorvos of the veterinary and agricultural formulations in chicks were 11.1 mg kg(-1) and 6.51 mg kg(-1) and those of diazinon 6.4 mg kg(-1) and 6.7 mg kg(-1). Plasma and brain cholinesterase activities were measured by electrometry after in vivo and in vitro exposure to organophosphates. The chicks showed signs of cholinergic toxicosis within one hour of dosing. Dichlorvos (8 mg kg(-1)) and diazinon (4 mg kg(-1)) in the veterinary and agricultural formulation significantly reduced both plasma and brain cholinesterase activities in the chicks. The veterinary formulation of dichlorvos reduced plasma ChE by 60% and agricultural by 40% and brain ChE by 93% and 87%, respectively. In contrast, ChE inhibition by diazinon in the agricultural formulation of diazinon was stronger than by the veterinary formulation; 72% vs. 64% in plasma and 97% vs. 80% in the brain, respectively. The highest in vitro inhibitions were observed with dichlorvos in the agricultural formulation (50%) in the brain samples and with diazinon in the agricultural formulation (52%) in the plasma samples. While they exist, differences between formulations cannot be taken as a rule and further investigations should inventory the toxicity of standard veterinary and agricultural organophosphate formulations in addition to the known data for pure forms.


Mechanical Properties of Rice Husk Biochar Reinforced High Density Polyethylene Composites.
Rice husk biochar was utilized to reinforce high-density polyethylene (HDPE) and to prepare biochar/plastic composites (BPC) by the extrusion method. Morphologies, non-isothermal crystallization behavior, and mechanical properties of the composites were investigated. The SEM (scanning electron microscope) showed that HDPE was embedded into the holes of the rice husk biochar. The DSC (differential scanning calorimeter) showed that biochar could reduce the crystallization rate and the higher the content of rice husk biochar, the slower the crystallization rate. Significantly, the bending and tensile strength of BPC could reach 53.7 and 20 MPa, far beyond WPC (wood plastic composites). With the increase of filler content, BPC were still stronger than WPC, although the impact strength of BPC and WPC all showed a general decline in the trend. The strong interaction was achieved by the utilization of rice husk biochar to reinforce HDPE.


Angiosarcomas of the head and neck: clinical and pathologic characteristics.
Between 1974 and 1992, 32 patients with pathologically diagnosed angiosarcoma of the head and neck were evaluated at our institution. The primary treatment group consisted of 24 patients who had the initial diagnosis made or confirmed at our institution, and the other 8 patients formed the salvage group. There were 23 men and 9 women. The median age in the primary treatment group was 63 years (range 18 to 91 years). The overall median survival among the primary group patients was 4.8 years, and the 3-year survival was estimated to be 57% (95% confidence interval 39% to 84%). The median follow-up was 2.1 years (range 83 days to 9.7 years). Patients who had tumors less than 7.0 cm in diameter and tumors with invasion only to the subcutaneous tissues had better overall survival and longer time to first adverse event. Diploid DNA content was a significant favorable prognostic factor for time to first adverse event. Mitotic activity was of borderline significance with both end points. Patients who had tumors of less than 1.5 cm were treated successfully with surgery alone. Patients treated with combined surgery and radiotherapy also tended to do better. Because most patients in whom regional recurrences developed had tumors larger than 7.0 cm, we conclude that patients with tumors of this size may benefit from regional neck node dissection at the time of primary excision or from elective neck irradiation.


[Wrist stability after experimental traumatic triangular fibrocartilage complex lesions].
To evaluate the changes in stability of the wrist after experimental traumatic triangular fibrocartilage complex (TFCC) lesions, and to provide basic theoretical criteria for clinical treatment. Fourteen adult cadaver upper extremities specimens were included. Two of 14 specimens were tested in pre-experiment. The specimens were tested in a INSTRON 8874 biomechanics measuring instrument. First a dorsal arthrotomy (ART) was performed, and second test was with 1 of 4 different experimental lesions according to Palmer's classification of traumatic TFCC lesions (n=3). 1A: central perforation; 1B: ulnar avulsion with or without fracture of processus styloideus ulnae; 1C: distal avulsion with ligament injury; 1D: radial avulsion. Forced internal external rotation torque were recorded in the interval -60 degrees to 60 degrees of flexion. The average torque of the dorsal ART was (0.713 +/- 0.121) Nm, and the 1B-1 lesion (ulnar avulsion without ulnar styloid fracture) was (0.709 +/- 0.134) Nm, the 1B-2 lesion (ulnar avulsion with ulnar styloid fracture) was (0.409 +/- 0.113) Nm. The difference between the 1B-1 lesion and the dorsal ART was not significant but the difference between the 1B-2 lesion and the dorsal ART was significant (P < 0.05). The average torque of the 1C lesion in about 45 degrees of wrist extension and flexion were (0.878 +/- 0.184) Nm and (0.988 +/- 0.197) Nm, and the dorsal ART were (1.510 +/- 0.173) Nm and (1.540 +/- 0.093) Nm. The difference between the two groups was significant (P < 0.05). The 1A lesion and 1D lesion did not alter significantly wrist stability. The 1B-2 lesion and 1C lesion alter significantly the stability of the wrist.


Two-dimensional finite quantum Hall clusters of electrons with anisotropic features.
Low-dimensional nano and two-dimensional materials are of great interest to many disciplines and may have a lot of applications in fields such as electronics, optoelectronics, and photonics. One can create quantum Hall phases by applying a strong magnetic field perpendicular to a two-dimensional electron system. One characterizes the nature of the system by looking at magneto-transport data. There have been a few quantum phases seen in past experiments on GaAs/AlGaAs heterostructures that manifest anisotropic magnetoresistance, typically, in high Landau levels. In this work, we model the source of anisotropy as originating from an internal anisotropic interaction between electrons. We use this framework to study the possible anisotropic behavior of finite clusters of electrons at filling factor 1/6 of the lowest Landau level.


[Research progress on the relationship between osteopontin and hepatic echinococcosis].
Osteopontin is a negatively charged, hydrophilic secreted phosphorylated glycoprotein. It is synthesized and secreted by a variety of cells, and is found in various tissues and cells. The protein is similar in structure to matrix proteins, has the characteristics of cytokines in function and involved in a series of pathological processes. Recent studies confirmed that osteopontin is highly expressed in liver hydatid cyst and may play an important role in cyst formation.


Diffusion weighted imaging distinguishes the vegetative state from the minimally conscious state.
The vegetative (VS) and minimally conscious (MCS) states are currently distinguished on the basis of exhibited behaviour rather than underlying pathology. Although previous histopathological studies have documented different degrees of diffuse axonal injury as well as damage to the thalami and brainstem regions in VS and MCS, these differences have not been assessed in vivo, and therefore, do not provide a measurable pathological marker to aid clinical diagnosis. Currently, the diagnostic decision-making process is highly subjective and prone to error. Indeed, previous work has suggested that up to 43% of patients in this group may be misdiagnosed. We used diffusion tensor imaging (DTI) to study the neuropathology of 25 vegetative and minimally conscious patients in vivo and to identify measures that could potentially distinguish the patients in these two groups. Mean diffusivity (MD) maps of the subcortical white matter, brainstem and thalami were generated. The MCS and VS patients differed significantly in subcortical white matter and thalamic regions, but appeared not to differ in the brainstem. Moreover, the DTI results predicted scores on the Coma Recovery Scale (p<0.001) and successfully classified the patients in to their appropriate diagnostic categories with an accuracy of 95%. The results suggest that this method may provide an objective and highly accurate method for classifying these challenging patient populations and may therefore complement the behavioural assessment to inform the diagnostic decision making process.


Enhanced expression of insulin-like growth factor binding protein-3 sensitizes the growth inhibitory effect of anticancer drugs in gastric cancer cells.
Insulin-like growth factor (IGF)-I and -II are potent mitogens and their mitogenic effects are modulated by IGF binding proteins (IGFBPs). In this study, we evaluated whether the enhanced expression of IGFBP-3 may increase the sensitivity of human gastric cancer cells to the anticancer drugs. We further investigated the potential mechanism for the growth inhibitory effect of anticancer drug induced-IGFBP-3 expression. These IGFBP-3-expressing gastric cancer cells showed a lower proliferation rate than IGFBP-3-non-expressing cells. Treatment with anticancer drugs resulted in up-regulation of IGFBP-3 expression in IGFBP-3-expressing cells. Interestingly the anticancer drug-induced-growth inhibition was more evident in IGFBP-3-expressing cells causing the IGFBP-3 expressing cells but not the IGFBP-3 non-expressing cells to accumulate in the G1/G0 phase and induce apoptosis. The exogenous addition of IGFBP-3 inhibited the growth of IGFBP-3-non-expressing cells, causing them to undergo apoptosis. Our data suggest that IGFBP-3 may have an important role in the biology of gastric cancer cell growth and provides a potential marker for predicting the responsiveness to anticancer drugs.


Thermodynamics of water intrusion in nanoporous hydrophobic solids.
We report a joint experimental and molecular simulation study of water intrusion in silicalite-1 and ferrerite zeolites. The main conclusion of this study is that water condensation takes place through a genuine first-order phase transition, provided that the interconnected pores structure is 3-dimensional. In the extreme confinement situation (ferrierite zeolite), condensation takes place through a continuous transition, which is explained by a shift of both the first-order transition line and the critical point with increasing confinement. The present findings are at odds with the common belief that conventional phase transitions cannot take place in microporous solids such as zeolites. The most important features of the intrusion/extrusion process can be understood in terms of equilibrium thermodynamics considerations. We believe that these findings are very general for hydrophobic solids, i.e. for both nonwetting as well as wetting water-solid interface systems.


Operation status of the electron cyclotron resonance ion source at Gunma University.
An ECR ion source of Gunma University Heavy Ion Medical Center, so-called KeiGM [M. Muramatsu, A. Kitagawa, Y. Sakamoto, S. Sato, Y. Sato, H. Ogawa, S. Yamada, H. Ogawa, Y. Yoshida, and A. G. Drentje, Rev. Sci. Instrum. 76, 113304 (2005)], has been operated for cancer therapy and physical/biological experiment since 2010. KeiGM produces typically 230 μA of 10 keV/u C(4+) ions from CH4 gases. The vacuum pressure is kept between 1.2 × 10(-4) and 1.7 × 10(-4) Pa so as to suppress the pulse-to-pulse current fluctuation within ±10%. The extraction electrode is cleaned every 6-8 months in order to remove deposited carbon, which increases the leak current and discharge. In order to investigate the possibility of long-term operation without such maintenances, oxygen aging for the cleaning of the extraction electrode has been tested in the test bench. The same-designed ion sources at National Institute of Radiological Sciences and SAGA Heavy Ion Medical Accelerator in Tosu (SAGA-HIMAT) are also operated with stable C(4+) current, which are suitable for the continuous operation for cancer therapy.


[Hepatotoxicity of antineoplastic agents].
The influence of various antineoplastic preparations (farmorubicin, paclitaxel, etoposide, platidiam) on morphological and functional status of the liver in experimental animals was studied. It is shown, that all these antineoplastic drugs possess strong hepatotoxic activity and thereby cause toxic hepatitis and increase activity of hepatic enzymes. Biochemical parameters were normalized within 30 days after treatment whereas morphological changes persisted somewhat longer.


Dominance of serotype Ia among group B Streptococci causing invasive infections in nonpregnant adults in Portugal.
The population of group B streptococci (GBS) associated with invasive infections in nonpregnant adults from 2001 to 2008 was analyzed in isolates submitted from 24 hospital laboratories in Portugal (n = 225). The isolates were characterized by antimicrobial susceptibility, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and surface protein gene profiling. GBS invasive cases were found more frequently among men in all age groups. In addition, serotype Ia was the most frequent in our collection, whereas serotype V is dominant elsewhere. Serotype Ia was represented mainly by a single PFGE cluster defined by sequence type 23 (ST23) and surface protein gene eps and by ST24 and bca, similarly to neonatal invasive infections in Portugal, indicating that the same genetic lineages can be responsible for both vaginal colonization and invasive disease in all age groups. In contrast, the hypervirulent serotype III/ST17 neonatal lineage was responsible for a minority of infections. Serotype V isolates were distributed into two genetic lineages, one defined by ST1 and surface protein gene alp3 and macrolide resistant, and another presenting with ST2 and eps and fully susceptible to all antimicrobials tested. The erm(TR) gene was the most frequently found among erythromycin-resistant isolates, while the bovine-associated tet(O) gene was found in a minority of tetracycline-resistant isolates. Our data emphasize the importance of local identification of the genetic lineages responsible for GBS invasive infections in nonpregnant adults. The dominance of serotype Ia in invasive disease in Portugal highlights the importance of this serotype in GBS pathogenesis.


Diboron and triboron compounds based on linear and star-shaped conjugated ligands with 8-hydroxyquinolate functionality: impact of intermolecular interaction and boron coordination on luminescence.
New 8-R-quinoline functionalized linear and star-shaped conjugated molecules have been synthesized using Suzuki-Miyaura coupling methods (R = MeO, L1-L5; R = CH3OCH2O, L1'-L5'). When treated with HCl, L1'-L5' are converted readily to the corresponding 8-hydroxyquinoline compounds L(OH)1-L(OH)5 which react readily with BPh3 in refluxing THF to produce the corresponding polyboron chelate compounds B1-B5 in good yields. L1-L5 and B1-B5 display similar thermal stability with Td at approximately 300 degrees C. Experimental and molecular orbital calculation results showed that the chelation by boron stabilizes the LUMO level of the ligand and narrows the HOMO-LUMO gap, resulting in the blue emission of the ligands and the green or orange emission of the boron compounds. Crystal structures of L1, L3, and L5 showed that these molecules have layered arrangements in the solid state with significant intermolecular pi-pi interactions. The linear diboron B5 displays concentration and temperature-dependent emission in solution, attributable to intermolecular interactions. The properties of a monoboron compound BPh2(5-Ph-8-MeO-q) (B0) and its corresponding free ligand L0 were investigated and compared to the closely related diboron compound B1 and the ligand L1, which revealed that the increase of the number of chromophores linked by an aromatic group has a significant impact on thermal stability and the HOMO and LUMO energy levels.


[Dr. Henry Wigderson--the first neurosurgeon in Eretz-Israel].
The vision of Hadassah Medical Organization and the Hebrew University in Jerusalem was to establish a University Hospital where clinical excellence and high academic level will be the hallmark of its departments. More than seventy years ago, guided by this spirit, the leaders of the two institutions attempted to establish a department of neurosurgery, which, at the time in only a few countries, was making its initial steps as an independent discipline. It was only during World War II that Hadassah could bring over a specialist in neurosurgery who worked for nearly three years in the Hadassah Hospital on Mount Scopus. This article describes the way Dr. Henry Wigderson was selected to be the first neurosurgeon in Eretz-Israel, his activities and the incorporation of the idea, in spite of the disappointment caused by his departure, that even at times of distress, neurosurgery is not a luxury but an indispensable part of an forward-looking medical institution.


Broadband, high-power, continuous-wave, mid-infrared source using extended phase-matching bandwidth in MgO:PPLN.
We report a compact and viable source of broadband, high-power, cw, mid-IR radiation based on a singly resonant optical parametric oscillator (SRO) pumped by a wide-bandwidth cw Yb fiber laser centered at 1060 nm. By exploiting the extended phase-matching bandwidth in a 50 mm crystal of MgO:PPLN and a ring SRO cavity, we obtain 5.3 W of broadband idler output for 25.5 W of pump at >80% depletion, transferring a pump bandwidth of 73.9 cm(-1) to an idler spectrum spread across an equal bandwidth centered at 3454 nm. By deploying output coupling of the signal, we generate 11.2 W of total power at 44% extraction efficiency with a pump depletion of >73% at the maximum available pump power. Measurements of transverse modal power confirm Gaussian distribution of signal and idler beams.