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A series of biodegradable copolymers based on polyaspartamide (PASPAM) were synthesized by grafting hydrophilic O-(2-aminoethyl)-O'-methylpoly(ethylene glycol) (MPEG), hydrophobic cholic acid (CA), and pH-sensitive hydrazone (Hyd) segments on a PASPAM backbone. The hydrazone group was effectively cleaved to release doxorubicin (DOX) conjugated on PASPAM in an acidic environment. The chemical structure of the polymer and the degree of substitution of each graft segment were analyzed using FT-IR and ¹H-NMR spectroscopy. The size of the MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates was examined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The mean diameter of the self-aggregates increased from 125 to 200 nm at pH 7.4, as the degree of substitution of CA increased from 10 to 20%. The release kinetics of DOX was strongly affected by the pH of the releasing medium. While less than 30% of the DOX loaded was released in about 30 h at pH 7.4, more than 60% was released at pH 5.0 within the same time. The viability tests of human breast cancer cells (MCF-7) and human embryonic kidney cells (293T) show the potential application of MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates in the controlled intracellular delivery for cancer treatment.

This paper reviews literature on the detrimental effect of combat-related posttraumatic stress disorder on the family. The literature indicates that guilt feelings, emotional withdrawal and elevated levels of aggression in the returning veteran make it difficult, perhaps even impossible, for him to fully resume his former roles of father, husband and breadwinner. Wives and children of veterans show psychiatric symptoms. Despite these hardships, the families are generally reluctant to seek professional help. The clinical implications are discussed and suggestions are made for intervention and outreach.

The ultimate goal for vaccination is to stimulate protective immunological memory. Protection against infectious diseases not only relies on the magnitude of the humoral immune response, but more importantly on the quality and longevity of it. Adjuvants are critical components of most non-living vaccines. Although little attention has been given to qualitative aspects of the choice of vaccine adjuvant, emerging data demonstrate that this function may be central to vaccine efficacy. In this review we describe efforts to understand more about how adjuvants influence qualitative aspects of memory development. We describe recent advances in understanding how vaccines induce long-lived plasma and memory B cells, and focus our presentation on the germinal center reaction. As mucosal vaccination requires powerful adjuvants, we have devoted much attention to the adenosine diphosphate (ADP)-ribosylating cholera toxin and the CTA1-DD adjuvants as examples of how mucosal adjuvants can influence induction of long-term memory.

The mechanical properties of the lungs were studied in two groups of coal miners. The first group consisted of miners with either simple or no pneumoconiosis and was divided into two subgroups (1A and 1B). The former (1A) consisted of 62 miners most of whom had simple pneumoconiosis but a few of whom had clear films. Although their spirometry was normal, all claimed to have respiratory symptoms. The other subgroup (1B) consisted of 25 working miners with definite radiographic evidence of simple pneumoconiosis but normal spirometric findings. The second major group consisted of 25 men with complicated pneumoconiosis. In subjects with simple pneumoconiosis, static compliance was mostly in the normal range, whereas it was often reduced in subjects with the complicated disease. The coefficient of retraction was normal or reduced in most subjects except those with advanced complicated disease, in several of whom it was elevated. So far as simple pneumoconiosis was concerned, abnormalities, when present, reflected "emphysema" rather than fibrosis. In severe complicated pneumoconiosis, changes suggesting fibrosis tended to predominate. In the 25 working miners (subgroup 1B) dynamic compliance was measured at different respiratory rates. 17 of the subjects in this subgroup demonstrated frequency dependence of their compliance, a finding unrelated to bronchitis and suggestive of increased resistance to flow in the smallest airways.

Enzalutamide, a second-generation small-molecule inhibitor of the androgen receptor (AR), has been approved for patients who failed with androgen deprivation therapy and have developed castration-resistant prostate cancer. More than 80% of these patients develop bone metastases. The binding of enzalutamide to the AR prevents the nuclear translocation of the receptor, thus inactivating androgen signaling. However, prostate cancer cells eventually develop resistance to enzalutamide treatment. Studies have found resistance both in patients and in laboratory models. The mechanisms of and approaches to overcoming such resistance are significant issues that need to be addressed. In this review, we focus on the major mechanisms of acquired enzalutamide resistance, including genetic mutations and splice variants of the AR, signaling pathways that bypass androgen signaling, intratumoral androgen biosynthesis by prostate tumor cells, lineage plasticity, and contributions from the tumor microenvironment. Approaches for overcoming these mechanisms to enzalutamide resistance along with the associated problems and solutions are discussed. Emerging questions, concerns, and new opportunities in studying enzalutamide resistance will be addressed as well.

Reactivation of 0² evolution function has been studied in PS-2 particles after complete removal of Mn and water soluble 10, 17, 24, 33 kDa proteins, It has been shown that 0² evolution function in such particles can be reactivated by adding 5 μM Mn² and 20 mM Ca²(+). Preliminary illumination of the sample is necessary to exhibit the reactivation effect of 0² evolution. The maximum value of the reactivation of 0² evolution rate is about 60% of the control. Upon illumination of the reactivated particles with flashes of 1s duration and at a frequency of 0,1 Hz, 0² evolution occurs according to the mechanism analogous to that in the initial parties of PS 2. Thus the reactivation of water oxidation and 0² evolution after complete removal of Mn and water soluble 10, 17, 24, 33 kDa proteins resulting in the suppression of 0² evolution function has been shown for the first time and it can serve as a basic approach for profound investigation of the mechanism of photosynthetic water oxidation.

Caulobacter crescentus (CB15) initiates chromosome replication only in stalked cells and not in swarmers. To better understand this dimorphic control of chromosome replication, we isolated replication origins (oris) from freshwater Caulobacter (FWC) and marine Caulobacter (MCS) species. Previous studies implicated integration host factor (IHF) and CcrM DNA methylation sites in replication control. However, ori IHF and CcrM sites identified in the model FWC CB15 were only conserved among closely related FWCs. DnaA boxes and CtrA binding sites are established CB15 ori components. CtrA is a two-component regulator that blocks chromosome replication selectively in CB15 swarmers. DnaA boxes and CtrA sites were found in five FWC and three MCS oris. Usually, a DnaA box and a CtrA site were paired, suggesting that CtrA binding regulates DnaA activity. We tested this hypothesis by site-directed mutagenesis of an MCS10 ori which contains only one CtrA binding site overlapping a critical DnaA box. This overlapping site is unique in the whole MCS10 genome. Selective DnaA box mutations decreased replication, while selective CtrA binding site mutations increased replication of MCS10 ori plasmids. Therefore, both FWC and MCS oris use CtrA to repress replication. Despite this similarity, phylogenetic analysis unexpectedly shows that CtrA usage evolved separately among these Caulobacter oris. We discuss consensus oris and convergent ori evolution in differentiating bacteria.

Fungal and oomycete pathogens cause many destructive diseases of plants and important diseases of humans and other animals. Fungal and oomycete plant pathogens secrete numerous effector proteins that can enter inside host cells to condition susceptibility. Until recently it has been unknown if these effectors enter via pathogen-encoded translocons or via pathogen-independent mechanisms. Here we review recent evidence that many fungal and oomycete effectors enter via receptor-mediated endocytosis, and can do so in the absence of the pathogen. Surprisingly, a large number of these effectors utilize cell surface phosphatidyinositol-3-phosphate (PI-3-P) as a receptor, a molecule previously known only inside cells. Binding of effectors to PI-3-P appears to be mediated by the cell entry motif RXLR in oomycetes, and by diverse RXLR-like variants in fungi. PI-3-P appears to be present on the surface of animal cells also, suggesting that it may mediate entry of effectors of fungal and oomycete animal pathogens, for example, RXLR effectors found in the oomycete fish pathogen, Saprolegnia parasitica. Reagents that can block PI-3-P-mediated entry have been identified, suggesting new therapeutic strategies.

Basic fibroblast growth factor (FGF2) is a potent mitogen for medial smooth muscle cells and is necessary for their proliferation after balloon catheter injury; however, intimal smooth muscle cells do not require FGF2 for their proliferation, and they respond only weakly to exogenous FGF2. The present study examined the activation of extracellular signal-regulated kinase (ERK) signaling as well as the expression and activity of cell cycle proteins in FGF2-stimulated intimal smooth muscle cells. FGF2 activates ERKs 1 and 2, and Western blot analysis showed that cyclin D, cyclin E, and cyclin-dependent kinase (CDKs) 2 and 4 were expressed in intimal smooth muscle cells after FGF2 infusion. FGF2 stimulation, however, did not lead to phosphorylation of the retinoblastoma protein (Rb), CDK 2 activation, or expression of cyclin A. Western blot analysis showed that intimal smooth muscle cells express elevated levels of the cell cycle inhibitors p15(INK4b) and p27(Kip1), compared with medial smooth muscle cells, and that FGF2 stimulation does not reduce the level of these inhibitors. These studies suggest that despite activation of ERKs 1 and 2 and expression of the cell cycle activators, cyclin D and cyclin E, high levels of cell cycle inhibitors may inhibit cell cycle transit in FGF2-stimulated intimal smooth muscle cells.

Solidification processing is essential to the manufacture of various metal products, including additive manufacturing. Solidification grain boundaries (SGBs) result from the solidification of the last liquid film between two abutting grains of different orientations. They can migrate, but unlike normal GB migration, SGB migration (SGBM) decouples SGBs from solidification microsegregation, further affecting material properties. Here, we first show the salient features of SGBM in magnesium-tin alloys solidified with cooling rates of 8-1690 °C/s. A theoretical model is then developed for SGBM in dilute binary alloys, focusing on the effect of solute type and content, and applied to 10 alloy systems with remarkable agreement. SGMB does not depend on cooling rate or time but relates to grain size. It tends to occur athermally. The findings of this study extend perspectives on solidification grain structure formation and control for improved performance (e.g. hot or liquation cracking during reheating, intergranular corrosion or fracture).

Neuromyelitis optica (NMO) is a disease characterised by severe relapses of optic neuritis and longitudinally extensive transverse myelitis and it has a strong female predilection. Pain is one of the most typical symptom in NMO. However, few studies have been conducted to examine the neuropathic pain mechanism of NMO patients or gender-specific effects using magnetic resonance imaging technique. A total of 38 female patients with NMO, 28 with pain (NMOWP) and 10 without pain (NMOWoP), were classified using the Brief Pain Inventory (BPI); 22 healthy females were also recruited. We used the FSL Image Registration and Segmentation Toolbox (FIRST) for subcortical region volumes quantifications, and voxel-based morphometry analysis for cortical gray matter (GM) volume, to examine the brain morphology in NMOWP patients. In addition, correlation test between structural measurements of NMO patients and clinical indexes was also performed. The results showed: 1) no significant differences in cortical GM density between the NMOWP and NMOWoP groups; 2) significantly smaller hippocampus and pallidum volumes in the NMOWP group compared with the NMOWoP group; 3) significant negative correlation between the average BPI and volumes of the accumbens nucleus and thalamus in NMO patients. These results revealed that structural abnormality exists in NMO female patients who have pain, with significant implications for our understanding of the brain morphology in NMO patients with pain.

We describe a secretion vector system for introducing foreign genes into Bacillus subtilis. We constructed secretion vectors from the plasmid pUB110 and the promoter and signal sequence region of the alpha-amylase gene from Bacillus amyloliquefaciens. Foreign structural genes can be inserted into the various vectors after the signal sequence region of the alpha-amylase gene. Demonstrating secretion of a foreign gene product from Bacillus, we here report that the Escherichia coli beta-lactamase gene, devoid of its own signal sequence coding region, can be expressed in B. subtilis by the aid of the secretion vectors so that greater than 95% of the enzyme activity is secreted to the growth medium. Efficient secretion of beta-lactamase (penicillin amido-beta-lactamhydrolase, EC 3.5.2.6) is observed if the complete signal sequence coding region of the alpha-amylase gene precedes the beta-lactamase structural gene. However, an incomplete alpha-amylase signal peptide lacking the six carboxy-terminal amino acid residues does not promote secretion of the fused beta-lactamase, which remains unprocessed and cell-associated.

We report a rare case of anterior pontine hydatid cyst. Diagnosis was established on magnetic resonance imaging (MRI) findings preoperatively and was confirmed during surgery and by laboratory findings of cyst fluid, and section of cyst wall. A classical suboccipital craniectomy was performed, followed by an approach through the floor of the fourth ventricle. After a failed attempt at the Dowling technique, we punctured the cyst, aspirated the contents, then extirpated the cyst membrane. The patient survived suffering only minor morbidity. The surgical technique and pontine myelotomy are discussed.

The amount of casein found in the milk of the tammar wallaby increases as lactation progresses. The increase is due to increasing amounts of beta-casein; the alpha-casein remains largely constant. The alpha-casein is the more highly phosphorylated; the most abundant form is the 10-P, throughout lactation. The level of phosphorylation of beta-casein shifts to lower average values in late lactation, possibly indicating the enzymatic reaction is overloaded by the increasing amounts of beta-casein. Unlike bovine casein micelles, the wallaby micelles are not completely disrupted at pH 7.0 by sequestration of their calcium content with ethylene diamine tetraacetic acid (EDTA). Complete disruption only follows the addition of sodium dodecyl sulphate, indicating considerably greater importance for hydrophobic bonds in maintaining their integrity. This micellar behaviour indicates that, despite the evolutionary divergence of marsupials millennia ago, the caseins of wallaby milk assemble into micelles in much the same fashion as in bovine milk.

The goal of this study was to describe seroreversion (SR) in a cohort of human immunodeficiency virus-exposed but uninfected infants. Groups of patients who seroreverted very early or late were examined for salient clinical and immunologic characteristics of the mother or infant. The mean time (+/- s.d.) to seroreversion by enzyme-linked immunoabsorbent assay (ELISA) was 50.1 +/- 14.8 weeks, or 11.6 months (n = 84); the range of times to antibody loss by ELISA was 17.9 to 82.0 weeks. The mean time to seroreversion by Western blot was 68.3 +/- 12.6 weeks, or 15.8 months (n = 51), with a range of 44.9 to 94.1 weeks. Initial anti-human immunodeficiency virus titer as measured by cord blood ELISA optical density (OD) was found to relate significantly to mean time to seroreversion. No relationship to time to seroreversion was demonstrated for gestational age, maternal or neonatal serum immunoglobulin concentrations, maternal CD4 cell counts, maternal alcohol consumption, infantile diarrhea or failure to thrive. The lengthy time to seroreversion seen here demonstrates the 1994 revised Centers for Disease Control and Prevention definition of human immunodeficiency virus infection (based on seropositivity by both ELISA and confirmatory tests persisting beyond 18 months of age) to be accurate in our population. We recommend Western blot testing be used as confirmation for positive ELISAs only after 18 months of age.

Metarhizium anisopliae is a complex of cryptic species with wide geographical distribution and versatile lifestyles. In this study, 45 isolates of the Metarhizium genus harbored in the "Colección de Hongos Entomopatógenos" of the "Centro Nacional de Referencia de Control Biológico" from different substrates, insect-host, and localities from Colima, Mexico, were phylogenetically identified using the 5'end of translation elongation factor 1-α (5'TEF) and intergenic nuclear region MzFG543igs. Seven species were recognized, M. acridum (n = 26), M. pemphigi (n = 1), and within the PARB and MGT clades: M. anisopliae (N = 7; sensu stricto: n = 2; sensu lato: n = 5), M. brunneum (n = 2), M. guizhouense (n = 2), M. pingshaense (n = 2), and M. robertsii (n = 5). Twenty-nine SSR markers were developed for M. acridum; according to the analysis of 12 polymorphic SSR loci, M. acridum showed low genetic diversity, revealing five genotypes with a dominant one (n = 21). Based on the analysis of 13 specific SSR loci, 14 genotypes were identified within the PARB and MGT clades. This study contributes to generating valuable information about the community structure and genotypic diversity of Metharhizum species in the state of Colima, Mexico.

Most thiopeptide antibiotics target the translational machinery: thiostrepton (ThS) and nosiheptide (NoS) target the ribosome and inhibit translation factor function, whereas GE2270A/T binds to the elongation factor EF-Tu and prevents ternary complex formation. We have used several in vitro translational machinery assays to screen a library of thiopeptide antibiotic precursor compounds and identified four families of precursor compounds that are either themselves inhibitory or are able to relieve the inhibitory effects of ThS, NoS, or GE2270T. Some of these precursors represent distinct compounds with respect to their ability to bind to ribosomes. The results not only provide insight into the mechanism of action of thiopeptide compounds but also demonstrate the potential of such assays for identifying lead compounds that might be missed using conventional inhibitory screening protocols.

G protein-coupled receptors (GPCRs) play stimulatory or modulatory roles in numerous physiological states and processes, including growth and development, vision, taste and olfaction, behavior and learning, emotion and mood, inflammation, and autonomic functions such as blood pressure, heart rate, and digestion. GPCRs constitute the largest protein superfamily in the human and are the largest target class for prescription drugs, yet most are poorly characterized, and of the more than 350 nonolfactory human GPCRs, over 100 are orphans for which no endogenous ligand has yet been convincingly identified. We here describe new live-cell assays that use recombinant GPCRs to quantify two general features of GPCR cell biology-receptor desensitization and resensitization. The assays employ a fluorogen-activating protein (FAP) reporter that reversibly complexes with either of two soluble organic molecules (fluorogens) whose fluorescence is strongly enhanced when complexed with the FAP. Both assays require no wash or cleanup steps and are readily performed in microwell plates, making them adaptable to high-throughput drug discovery applications.

High-grade gliomas (HGGs) are malignant tumors and typically include glioblastoma multiforme and anaplastic astrocytoma subtypes. Brainstem gliomas and ependymomas are separate entities with respect to clinical presentation, treatment, prognosis, and outcome in comparison with supratentorial HGGs. In children, these tumors account for 3% to 7% of newly diagnosed brain tumors and 20% of all diagnoses of pediatric supratentorial brain tumors. These neoplasms are highly proliferative and mitotically active and of glial origin. This article reviews clinical, diagnostic, and pathologic features of HGG and current treatments and potential future therapies specific to pediatric patients with HGGs.

The American Heart Association is championing a national effort to make automated external defibrillators available to the public. Clinicians are beginning to grapple with the complexities involved in training laypersons to use these devices. The article reviews the experience of researchers involved in such training. Suggestions for training of nontraditional responders are derived from a review of the literature and are integrated with suggestions from active field investigators and the participants in a workshop on this topic held during the American Heart Association Public Access Defibrillation II Conference in Washington, DC (April 17-19, 1997). So far, widespread training of traditional first responders such as police and firefighters to use automated external defibrillators appears to be safe and effective. The data from studies in which nontraditional responders were trained are not as convincing. Further research is needed before we can assume that training of the public will be as easy and effective as training of traditional first responders.

We studied the time course of serum IgG antibodies against 3 different pertussis vaccine antigens: PT (pertussis toxin), FHA (filamentous hemagglutinin), Prn (pertactin) in sera from individuals vaccinated with four different pertussis vaccines at 4 years of age: (N=44, 44, 23 and 23, respectively,) and compared the responses to/after natural infection with Bordetella pertussis (N=44, age 1-8 years). These longitudinal data were analyzed with a novel method, using a mathematical model to describe the observed responses, and their variation among subjects. This allowed us to estimate biologically meaningful characteristics of the serum antibody response, like peak level and decay rate, and to compare these among natural infections and vaccine responses. Compared to natural infection, responses to PT after vaccination with the tested vaccines are smaller in magnitude and tend to decay slightly faster. When present in vaccines, FHA and Prn tend to produce high peak levels, higher than those in naturally infected patients, but these decay faster. As expected, the Dutch whole cell vaccine produced lower antibody responses than the acellular vaccines. This model allows a better comparison of the kinetics of vaccine induced antibody responses and after natural infection over a long follow up period.

The function of populations of nociceptors in muscle pain syndromes remain poorly understood. We compared the contribution of two major classes, isolectin B4-positive (IB4(+)) and IB4-negative (IB4(-)) nociceptors, in acute and chronic inflammatory and ergonomic muscle pain. Baseline mechanical nociceptive threshold was assessed in the gastrocnemius muscle of rats treated with IB4-saporin, which selectively destroys IB4(+) nociceptors. Rats were then submitted to models of acute inflammatory (intramuscular carrageenan)- or ergonomic intervention (eccentric exercise or vibration)-induced muscle pain, and each of the three models also evaluated for the transition from acute to chronic pain, manifest as prolongation of prostaglandin E2 (PGE(2))-induced hyperalgesia, after recovery from the hyperalgesia induced by acute inflammation or ergonomic interventions. IB4-saporin treatment did not affect baseline mechanical nociceptive threshold. However, compared to controls, IB4-saporin treated rats exhibited shorter duration mechanical hyperalgesia in all three models and attenuated peak hyperalgesia in the ergonomic pain models. And, IB4-saporin treatment completely prevented prolongation of PGE(2)-induced mechanical hyperalgesia. Thus, IB4(+) and IB4(-) neurons contribute to acute muscle hyperalgesia induced by diverse insults. However, only IB4+ nociceptors participate in the long term consequence of acute hyperalgesia.

Forty four subjects were treated for benzodiazepine dependence. The withdrawal programme lasted for 10 weeks and included regular group support sessions. Patients were also treated with either propranolol, placebo or "no pill" under double blind conditions. Twenty three patients complied with the full treatment regimen and completed the trial. The outcome of treatment was moderately successful, with 8 out of the 23 patients stopping their tranquilizers and a further 11 achieving a reduction of 50% or more of their original benzodiazepine dose. Tranquilizer dependence is a difficult condition to treat, but preliminary results suggest that propranolol is helpful in reducing the symptoms of benzodiazepine withdrawal.

The effect of prior urinary tract obstruction on total CO2 flux in cortical and medullary collecting tubules was examined using an unilateral ureteral obstruction model and isolated tubule in vitro microperfusion. Tubules were obtained from the control and obstructed kidneys after 1, 2, and 4 days of obstruction. Paired comparison of function of cortical or medullary tubules and urine pH was made. Medullary collecting tubules showed decreased acidification after 2 days of obstruction (7.7 +/- 8.5 vs. 29.9 +/- 6.6 pmol/mm/min). Cortical collecting tubules from the obstructed kidney showed high rates of acidification at all time periods examined, and rates from the postobstructed cortical collecting tubules exceeded levels from control tubules at the 24-hour period while barely missing significance (p less than 0.06) at the 48- and 96-hour periods. These data are not consistent with the hypothesis that the acidification defect in the postobstructed kidney occurs in the cortical collecting tubule by a voltage-dependent mechanism.

Dry friction and wear tests were performed on as-cast Mg97Zn1Y2 alloy using a pin-on-disc configuration. Coefficients of friction and wear rates were measured as a function of applied load at sliding speeds of 0.2, 0.8 and 3.0 m/s. The wear mechanisms were identified in the mild and severe wear regimes by means of morphological observation and composition analysis of worn surfaces using scanning electron microscope (SEM) and energy dispersive X-ray spectrometer (EDS). Analyses of microstructure and hardness changes in subsurfaces verified the microstructure transformation from the deformed to the dynamically recrystallized, and properties changed from the strain hardening to dynamic crystallization (DRX) softening before and after the mild-severe wear transition. The mild-severe wear transition can be determined by a proposed contact surface DRX temperature criterion, from which the critical DRX temperatures at different sliding speeds are calculated using DRX dynamics; hence transition loads can also be calculated using a transition load model. The calculated transition loads are in good agreement with the measured ones, demonstrating the validity and applicability of the contact surface DRX temperature criterion.

Seven-transmembrane receptor (7-TMR)-G protein networks are molecular sensors of extracellular signals in all eukarya. These pathways cycle through activated (sensitized) and inhibited (desensitized) states, and, while many of the molecular components for signal activation have been described, inhibitory mechanisms are not well characterized. In Dictyostelium, 7-TM cAMP receptors direct chemotaxis and development but also regulate the periodic synthesis of their own ligand, the chemoattractant/morphogen cAMP. We now demonstrate through loss-of-function/gain-of-function studies that the novel heterotrimeric Galpha9 protein subunit regulates an inhibitory pathway during early Dictyostelium development for the cAMP signal response.

NADH shuttles, including malate-aspartate shuttle (MAS) and glycerol-3-phosphate shuttle, can shuttle the reducing equivalents of cytosolic NADH into mitochondria. It is widely accepted that the major function of NADH shuttles is to increase mitochondrial energy production. Our study tested the hypothesis that the novel major function of NADH shuttles in cancer cells is to maintain glycolysis by decreasing cytosolic NADH/NAD(+) ratios. We found that AOAA, a widely used MAS inhibitor, led to decreased intracellular ATP levels, altered cell cycle and increased apoptosis and necrosis of C6 glioma cells, without affecting the survival of primary astrocyte cultures. AOAA also decreased the glycolytic rate and the levels of extracellular lactate and pyruvate, without affecting the mitochondrial membrane potential of C6 cells. Moreover, the toxic effects of AOAA were completely prevented by pyruvate treatment. Collectively, our study has suggested that AOAA may be used to selectively decrease glioma cell survival, and the major function of MAS in cancer cells may be profoundly different from its major function in normal cells: The major function of MAS in cancer cells is to maintain glycolysis, instead of increasing mitochondrial energy metabolism.

Two deoxysugar glycosyltransferases (GTs), UrdGT1b and UrdGT1c, involved in urdamycin biosynthesis share 91% identical amino acids. However, the two GTs show different specificities for both nucleotide sugar and acceptor substrate. Generally, it is proposed that GTs are two-domain proteins with a nucleotide binding domain and an acceptor substrate site with the catalytic center in an interface cleft between these domains. Our work aimed at finding out the region responsible for determination of substrate specificities of these two urdamycin GTs.

There are concerns around safety and tolerance of powder human milk fortifiers to optimize nutrition in preterm infants. The purpose of this study was to evaluate the tolerance and safety of a concentrated preterm formula (CPF) as a liquid human milk fortifier (HMF) for premature infants at increased risk of feeding intolerance. We prospectively enrolled preterm infants over an 18-month period, for whom a clinical decision had been made to add CPF to human milk due to concerns regarding tolerance of powder HMF. Data on feed tolerance, anthropometry, and serum biochemistry values were recorded. Serious adverse events, such as mortality, necrotizing enterocolitis (NEC), and sepsis, were monitored. A total of 29 babies received CPF fortified milk during the study period. The most common indication for starting CPF was previous intolerance to powder HMF. Feeding intolerance was noted in 4 infants on CPF. The growth velocity of infants was satisfactory (15.9 g/kg/day) after addition of CPF to feeds. The use of CPF as a fortifier in preterm babies considered at increased risk for feed intolerance seems well tolerated and facilitates adequate growth. Under close nutrition monitoring, this provides an additional option for human milk fortification in this challenging subgroup of preterm babies, especially in settings with limited human milk fortifier options.

Brown fat is a thermogenic organ that allows newborns and small mammals to maintain a stable body temperature when exposed to cold. The heat generation capacity is based on the uncoupling of respiration from ATP synthesis mediated by the uncoupling protein UCP1. The first studies on the properties of these mitochondria revealed that fatty acid removal was an absolute prerequisite for respiratory control. Thus fatty acids, that are substrate for oxidation, were proposed as regulators of respiration. However, their ability to uncouple all types of mitochondria and the demonstration that several mitochondrial carriers catalyze the translocation of the fatty acid anion have made them unlikely candidates for a specific role in brown fat. Nevertheless, data strongly argue for a physiological function. First, fatty acids mimic the noradrenaline effects on adipocytes. Second, there exists a precise correlation between fatty acid sensitivity and the levels of UCP1. Finally, fatty acids increase the conductance by facilitating proton translocation, a mechanism that is distinct from the fatty acid uncoupling mediated by other mitochondrial carriers. The regulation of UCP1 and UCP2 by retinoids and the lack of effects of fatty acids on UCP2 or UCP3 are starting to set differences among the new uncoupling proteins.

Chromatin immunoprecipitation (ChIP-Seq) has emerged as a superior alternative to microarray technology as it provides higher resolution, less noise, greater coverage and wider dynamic range. While ChIP-Seq enables probing of DNA-protein interaction over the entire genome, it requires the use of sophisticated tools to recognize hidden patterns and extract meaningful data. Over the years, various attempts have resulted in several algorithms making use of different heuristics to accurately determine individual peaks corresponding to unique DNA-protein. However, finding all the significant peaks with high accuracy in a reasonable time is still a challenge. In this work, we propose the use of Multi-level thresholding algorithm, which we call LinMLTBS, used to identify the enriched regions on ChIP-Seq data. Although various suboptimal heuristics have been proposed for multi-level thresholding, we emphasize on the use of an algorithm capable of obtaining an optimal solution, while maintaining linear-time complexity. Testing various algorithm on various ENCODE project datasets shows that our approach attains higher accuracy relative to previously proposed peak finders while retaining a reasonable processing speed.

Detection of <i>Streptococcus pneumoniae</i> antigen in cerebrospinal fluid (CSF) using lateral flow immunochromatography tests (ICTs) is an effective, rapid and low-cost method to diagnose pneumococcal meningitis. This study evaluated the diagnostic accuracy of the Uni-Gold ICT to detect pneumococcal antigen in CSF specimens, compared with gold standard bacteriology and quantitative real-time PCR (qPCR) testing. CSF specimens (n=69) from patients with suspected bacterial meningitis were included in the study. 13/69 (19%) were positive and 56/69 (81%) were negative for pneumococcus by the gold standard tests. The ICT had sensitivity of 85% (55%-98%), specificity of 96% (88%-100%), positive likelihood ratio of 23.7 (6-94) and negative likelihood ratio of 0.16 (0.04-0.57). Overall, a strong correlation between the ICT and qPCR results was seen (&#954;=0.81). In contrast, CSF microscopy and culture were exceptionally insensitive. The ICT method is sufficiently robust and accurate for use in algorithms to diagnose bacterial meningitis.

MicroRNA-101(miR-101) has been shown to be down-regulated in hepatocellular carcinoma (HCC). The hepatitis B virus (HBV) is a major risk factor in the development and progression of HCC. However, the correlation between HBV and miR-101 has not yet been fully elucidated. In this study, we reported that HBV could repress miR-101-3p by inhibiting its promoter activity and identified the potential effects of miR-101-3p on some important biological properties of HCC cells by targeting Rap1b. Dual-luciferase reporter assays showed that HBV down-regulated miR-101-3p by inhibiting its promoter activity. Down-regulation of miR-101-3p promoted cell proliferation, migration, and reduced apoptosis, and resulted in up-regulation of Rap1b, while overexpression of miR-101-3p inhibited these processes. Moreover, overexpression of Rap1b was able to reverse the suppressed cell proliferation and migration mediated by miR-101-3p. Our data showed that HBV down-regulated miR-101-3p expression by inhibiting its promoter activity, which resulted in up-regulation of Rap1b, and down-regulation of miR-101-3p or up-regulation of Rap1b promoted proliferation and migration of HCC cells. This provides a new understanding of the mechanism of HBV-related HCC pathogenesis and the potential application of miR-101-3p in cancer therapy.

Value-based health care is increasingly promoted as a strategy for improving care quality by benchmarking outcomes that matter to patients relative to the cost of obtaining those outcomes. To support the shift toward value-based health care in chronic kidney disease (CKD), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international working group of health professionals and patient representatives to develop a standardized minimum set of patient-centered outcomes targeted for clinical use. The considered outcomes and patient-reported outcome measures were generated from systematic literature reviews. Feedback was sought from patients and health professionals. Patients with very high-risk CKD (stages G3a/A3 and G3b/A2-G5, including dialysis, kidney transplantation, and conservative care) were selected as the target population. Using an online modified Delphi process, outcomes important to all patients were selected, such as survival and hospitalization, and to treatment-specific subgroups, such as vascular access survival and kidney allograft survival. Patient-reported outcome measures were included to capture domains of health-related quality of life, which were rated as the most important outcomes by patients. Demographic and clinical variables were identified to be used as case-mix adjusters. Use of these consensus recommendations could enable institutions to monitor, compare, and improve the quality of their CKD care.

To assess the exocrine pancreatic function in beta-thalassemia major with iron overload, serum immunoreactive trypsin (IRT) was measured in 38 patients with this condition. In 23 (60%) patients' IRT was abnormal: it was subnormal in 16 patients and supranormal in seven. Whereas subnormal IRT concentrations were more frequent in patients of more than 12 years old, supranormal IRT concentrations were more frequent in younger patients. These data provide the first antemortem evidence of exocrine pancreatic damage in this condition. They also suggest that this acinar cell damage is initially associated with a rise in IRT which is followed by a fall in the serum concentration of this enzyme.

Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P = 0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47-83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats.

The fine structure of the rotational ground state of molecular ortho-hydrogen confined inside the fullerene cage C60 is investigated by inelastic neutron scattering (INS). The INS line corresponding to transitions between the three sub-levels comprising the ortho ground state to the non-degenerate para ground state was studied as a function of temperature down to 60 mK in neutron energy gain. The experiments show that at ambient pressure the three ortho sub-levels are split into a low energy non-degenerate level and a high energy doubly degenerate level separated by 0.135 ± 0.010 meV. This observation is consistent with hydrogen molecules being located at sites with axial symmetry superseding the icosahedral symmetry of isolated rigid C60 cages in the solid phase. To gain insight into the role of inter-cage interactions in determining the symmetry breaking potential, the effects of hydrostatic pressure on the fine structure of the line was also investigated. The analysis of the INS spectra shows that the potential and the energy levels of H2 are sensitive to the orientation of neighbouring cages, consistent with the low-temperature crystalline phase of C60.

A comparison among various histological techniques for the detection of the parasite Bonamia ostreae in oysters Ostrea edulis was performed to evaluate their sensitivity and suitability for different purposes. The comparison involved examination of histological sections, tissue imprints from gills, digestive gland, gonad and heart, and haemolymph cell monolayers, prepared through various protocols. Every technique produced some false negative. The haemolymph cell monolayers were more sensitive than tissue imprints and histological sections. Heart imprints provided the highest sensitivity among tissue imprints. Examination of histological sections was among the least sensitive techniques. Four procedures for estimation of infection intensity were compared. Some differences in accuracy for the estimation of infection intensity between haemolymph cell monolayers and histological sections (HS) were detected: there was a very good agreement when the infection appeared low or heavy in HS but it was not so good in the remaining cases. The results suggest the need for a critical review of the recommendations of the "Office Internationale des Epizooties" and the European Union for diagnosis of bonamiosis.

Obesity is an epidemic health problem in many developed countries, and it is an emerging public health concern in developing, transitional, and newly developed countries. The purpose of this research is to investigate the relationship between individuals' knowledge concerning the health risks of obesity and their tendency to be obese (as measured by the "body mass index"). Instead of assuming that obesity is a pure physiological problem as in previous studies, we allow an individual's cost/benefit evaluation to play a role. Based on survey data from Taiwan, we investigate the relationship with the quantile regression technique. The results suggest that such a relationship does exist and it is different for males and females.

An 8-month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin) and pergolide (PRG; Permax) as add-on to L-dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non-demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinson's disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self - Rating Depression Scale by Zung were evaluated in an open-label design. The average value of Zung scores decreased significantly in both groups with no statistical difference between both groups. A significant decrease in the average value of MADRS scores was present only in the PPX group. The average UPDRS scores decreased significantly with no statistical difference between both groups at the comparable average total daily dose of both preparations. In both cases, the total daily dose of L-dopa decreased significantly but the decrease was statistically more pronounced in the PRG group. Our results demonstrate the antidepressant effect of PPX in patients with PD while we can't make any conclusions with regard to antidepressant effect of PRG.

Irish medical students have a long and proud history of embarking on international health electives (IHEs) to broaden their experience in the developing world. Although there are many opinions in the literature about IHEs, there is a dearth of empirical research that explores the experience and the value of these experiences to medical students. Most students who participate in these IHEs from Irish medical schools are members of student IHE societies, which are entirely run by students themselves. There are varying levels of preparation and interaction with the medical schools in planning these experiences. This study explores the experiences of a sample of students who completed IHEs in 2012.

The applicability of the auditory fatigue and anoxia hypotheses for the refractory period observed after sound-induced seizure was examined in SJL/J mice. Duration of auditory stimulation was varied independent of attainment of clonic seizure activity by use of an acoustic interruption technique. Duration of the recovery period affected the pattern of preconvulsive running. Furthermore, the motor asymmetries exhibited during clonus remained consistent across tests. Because duration of acoustic stimulation and attainment of clonus did not affect recovery rate, we conclude that neither the auditory fatigue nor the anoxia hypothesis provides a complete account for the refractory period after audiogenic seizure. We suggest that an inhibitory process, activated before clonus occurs and perhaps linked to depletion of excitatory amino acids in the inferior colliculus, may also be involved.

Findings from prior investigations show that left stellate ganglion (LSG) inhibitory approaches protect the heart from ventricular arrhythmias (VAs) caused by acute myocardial infarction (AMI), which still remain many side effects. Targeted transient receptor potential vanilloid 1/tyrosine hydroxylase (TRPV-1/TH) expressing sympathetic neurons ablation is a novel neuro-ablative strategy. The aim of this investigation was to explore if targeted molecular neuro-ablative strategy by resiniferatoxin (RTX) stellate microinjection could protect against ischemia-induced VAs.

Guided by emotional security theory, this study examined the temperamental precursors of distinctive profiles of children's responses to interparental conflict. Participants included 243 children (M = 4.6 years) and their parents across two annual measurement occasions. Temperamental constructs of frustration proneness, approach, positive affect, activity level, and effortful control were assessed through multiple methods, informants, and contexts. Behavioral observations of children's responses to interparental conflict at each wave yielded four profiles: secure (i.e., efficiently address direct threat), mobilizing (i.e., vigilance to potential threat and social opportunities), dominant (i.e., directly defeat threat), and demobilizing (i.e., reduce salience as a target of hostility). Results supported hypotheses on the distinct constellations of temperament in predicting subsequent change in the four security profiles.

We measured the concentrations of haloperidol and its reduced alcohol metabolite in human post-mortem tissues with high-performance/liquid chromatography using electrochemical detection. Both haloperidol and reduced haloperidol were detected and quantified in the occipital cortex of nine schizophrenic patients with a history of haloperidol treatment, but not in six samples from nontreated subjects. Reduced haloperidol concentrations were below the detection limit of the assay in several tissues of rats and mice even after 10 days of haloperidol treatment. The results suggest that reduced haloperidol is present in the brains of haloperidol-treated patients at slightly higher concentrations than haloperidol itself. Further studies are warranted to establish the possible biological importance of this haloperidol metabolite.

Ayahuasca is a psychedelic brew originally used for magico-religious purposes by Amerindian populations of the western Amazon Basin. Throughout the last four decades, the use of ayahuasca spread towards major cities in all regions of Brazil and abroad. This trend has raised concerns that regular use of this N,N-dimethyltryptamine- and harmala-alkaloid-containing tea may lead to mental and physical health problems associated typically with drug abuse. To further elucidate the mental and physical health of ayahuasca users, we conducted a literature search in the international medical PubMed database. Inclusion criteria were evaluation of any related effect of ayahuasca use that occurred after the resolution of acute effects of the brew. Fifteen publications were related to emotional, cognitive, and physical health of ayahuasca users. The accumulated data suggest that ayahuasca use is safe and may even be, under certain conditions, beneficial. However, methodological bias of the reviewed studies might have contributed to the preponderance of beneficial effects and to the few adverse effects reported. The data up to now do not appear to allow for definitive conclusions to be drawn on the effects of ayahuasca use on mental and physical health, but some studies point in the direction of beneficial effects. Additional studies are suggested to provide further clarification.

Here we report a new class of bio-inspired solid-liquid adhesive, obtained by simple mechanical dispersion of PVDF (polyvinylidene fluoride) (solid spheres) into PDMS (polydimethylsiloxane) (liquid). The adhesive behavior arises from strong solid-liquid interactions. This is a chemical reaction free adhesive (no curing time) that can be repeatedly used and is capable of instantaneously joining a large number of diverse materials (metals, ceramic, and polymer) in air and underwater. The current work is a significant advance in the development of amphibious multifunctional adhesives and presents potential applications in a range of sealing applications, including medical ones.

Students with autism often show challenges in social communication, particularly in initiating and responding behaviors. While the classroom offers a natural context for peer interactions, few interventions are designed specifically for classroom settings. This study investigated the effects of a classroom-teacher implemented social communication intervention, known as Social Stations, on the initiating and responding behaviors of students with autism. The study was set in an inclusive primary school, with the teacher embedding the intervention into the student's daily literacy lessons. All students with autism showed significant improvements in the targeted behaviors, with improvements maintained over time. This study suggests that social communication interventions can be implemented by teachers as part of a daily classroom program.

Pair bonding leads to increases in dopamine D1 receptor (D1R) binding in the nucleus accumbens of monogamous prairie voles. In the current study, we hypothesized that there is similar up-regulation of D1R in a monogamous primate, the titi monkey (Callicebus cupreus). Receptor binding of the D1R antagonist [¹¹ C]-SCH23390 was measured in male titi monkeys using PET scans before and after pairing with a female. We found that within-subject analyses of pairing show significant increases in D1R binding in the lateral septum, but not the nucleus accumbens, caudate, putamen, or ventral pallidum. The lateral septum is involved in a number of processes that may contribute to social behavior, including motivation, affect, reward, and reinforcement. This region also plays a role in pair bonding and paternal behavior in voles. Our observations of changes in D1R in the lateral septum, but not the nucleus accumbens, suggest that there may be broadly similar dopaminergic mechanisms underlying pair bonding across mammalian species, but that the specific changes to neural circuitry differ. This study is the first research to demonstrate neuroplasticity of the dopamine system following pair bonding in a non-human primate; however, substantial variability in the response to pairing suggests the utility of further research on the topic.

The modulation of P-glycoprotein's (Pgp) ATPase activity and its ability to regulate swelling-activated 125I efflux, by PKC alpha and PKC epsilon, was examined in insect cells. Recombinant baculovirus was used to express human Pgp in Sf9 cells and Pgp was also coexpressed with either PKC alpha or PKC epsilon. ATPase assays showed the enzyme activity of Pgp to be elevated during co-expression with the Ca2+ dependent isoform PKC alpha, but not with the Ca2+ independent variant PKC epsilon. Furthermore, neither isoform, when co-expressed with Pgp, altered the swelling-activated efflux of 125I from Sf9 cells. However, in cells co-expressing Pgp/PKC (alpha or epsilon), pre-treatment with the phorbol ester TPA significantly reduced the swelling-activated 125I efflux with both PKC isoforms. Our results suggest that phosphorylation with the Ca2+ independent variant PKC epsilon does not regulate the ATPase activity of Pgp and that stimulation of PKC with TPA alters the swelling-activated efflux of anions from insect cells expressing Pgp.

Ulcerative colitis is a chronic inflammatory disease of the colon that affects the rectum and a variable length of contiguous colon. The disease is characterized by rectal bleeding and diarrhea during periods of exacerbation; these symptoms usually abate with treatment. The pathogenic mechanism of ulcerative colitis is believed to be an aberrant immune response in which antibodies are formed against colonic epithelial protein(s). The disease usually presents during the second and third decades of life, with a smaller peak after the age of 60 years. There is a genetic component to ulcerative colitis, with a higher incidence among family members and, particularly, first-degree relatives. Diagnosis depends on several factors, most notably symptoms, demonstration of uniformly inflamed mucosa beginning in the rectum, and exclusion of other causes of colitis, such as infection. There is no medical cure for ulcerative colitis, but medical therapy is effective and can improve or eliminate symptoms in more than 80% of patients. Surgery offers a cure but carries the high price of total colectomy. New surgical methods, such as ileoanal anastomosis, allow for maintenance of bowel continuity and better patient satisfaction.

The development of disseminated (miliary) abdominal tuberculosis (TB) in patients following operations which affect their immunity, such as laparoscopic gastric bypass, is rare. The authors report the case of middle aged woman, who a few months after undergoing laparoscopic gastric bypass surgery for morbid obesity (body mass index 49), presented with generalised fatigability and abnormal liver function. A CT scan of the abdomen was suggestive of miliary TB. The patient developed acute abdomen pain. Intraoperative findings included perforated stomal ulcers at the gastrojejunostomy, diffuse micronodular involvement of the liver and spleen and thickened omentum. The perforation was closed and liver and omental biopsies were taken. Histology results from the liver and omentum revealed necrotising granulomatous inflammation suggestive of TB. Abdominal TB is a relatively rare manifestation of extrapulmonary TB. However, this diagnosis should be considered in patients immunocompromised due to immunosuppressive medication or operations affecting their nutrition. Early diagnosis and effective treatment of abdominal TB may decrease morbidity and mortality in such patients.

Rheumatologic diseases are associated with a proinflammatory state, which is thought to lead to many of the bone changes seen in treatment-naive patients. However, glucocorticoids remain a common treatment option for rheumatologic diseases and are known to have a negative impact on bone through direct effects on bone cells and indirect effects on calcium absorption. Despite the anti-inflammatory effect of glucocorticoids, fracture risk rises within the first 3 months of treatment. As such, osteoporosis prevention and treatment needs to be considered in all patients started on chronic glucocorticoids (≥3 months of treatment). For very low risk patients, conservative management with non-pharmacologic strategies may be appropriate. For the moderate to high fracture risk patients treated with glucocorticoids, pharmacologic treatment with 1 of the 4 approved medications should be considered. The challenge of educating physicians and patients of the risks of glucocorticoid induced osteoporosis remain.

Over 10 years ago, the Office of Food Additive Safety (OFAS) in the FDA's Center for Food Safety and Applied Nutrition implemented the formal use of structure-activity relationship analysis and quantitative structure-activity relationship (QSAR) analysis in the premarket review of food-contact substances. More recently, OFAS has implemented the use of multiple QSAR software packages and has begun investigating the use of metabolism data and metabolism predictive models in our QSAR evaluations of food-contact substances. In this article, we provide an overview of the programs used in OFAS as well as a perspective on how to apply multiple QSAR tools in the review process of a new food-contact substance.

Entorrhiza is a small fungal genus comprising 14 species that all cause galls on roots of Cyperaceae and Juncaceae. Although this genus was established 130 years ago, crucial questions on the phylogenetic relationships and biology of this enigmatic taxon are still unanswered. In order to infer a robust hypothesis about the phylogenetic position of Entorrhiza and to evaluate evolutionary trends, multiple gene sequences and morphological characteristics of Entorrhiza were analyzed and compared with respective findings in Fungi. In our comprehensive five-gene analyses Entorrhiza appeared as a highly supported monophyletic lineage representing the sister group to the rest of the Dikarya, a phylogenetic placement that received but moderate maximum likelihood and maximum parsimony bootstrap support. An alternative maximum likelihood tree with the constraint that Entorrhiza forms a monophyletic group with Basidiomycota could not be rejected. According to the first phylogenetic hypothesis, the teliospore tetrads of Entorrhiza represent the prototype of the dikaryan meiosporangium. The alternative hypothesis is supported by similarities in septal pore structure, cell wall and spindle pole bodies. Based on the isolated phylogenetic position of Entorrhiza and its peculiar combination of features related to ultrastructure and reproduction mode, we propose a new phylum Entorrhizomycota, for the genus Entorrhiza, which represents an apparently widespread group of inconspicuous fungi.

1. Two distinct lysophospholipases have previously been obtained in homogeneous form from beef liver. In this paper, we demonstrate that ageing of a beef liver homogenate does not result in a change in the ratio of the two enzymatic activities, indicating that no interconversion of the lysophospholipases took place. 2. Possible partial structural relationships between the two enzymes were explored by immunochemical techniques. Rabbit antisera raised against each individual lysophospholipase showed no cross-reactivity with the other enzyme. This was concluded from immuno double-diffusion experiments and from the results of immunoprecipitation of enzymatic activities in solution. 3. Lysophospholipase and esterase activity in the purified preparation of lysophospholipase II from beef liver were concomitantly precipitated by anti-serum against lysophospholipase II. This is further proof that both enzymatic activities reside in a single polypeptide chain, in agreement with previous results of isoelectric focusing experiments.

Though enlargement of the bony orbit by orbital decompression surgery has been known for about a century, surgical techniques vary all around the world mostly depending on the patient's clinical presentation but also on the institutional habits or the surgeon's skills. Ideally every surgical intervention should be tailored to the patient's specific needs. Therefore the aim of this paper is to review outcomes, hints, trends, and perspectives in orbital decompression surgery in thyroid eye disease regarding different surgical techniques.

The diagnostic accuracy of graded stress radiography in 26 patients with acute injury to the lateral ankle ligaments has been compared with findings at arthrography and surgery. Measuring talar tilt angles and anterior talar displacement over a range of pressures applied to the distal tibia using a commercially available stress device allows diagnostic distinction between isolated anterior talofibular ligament injury and a combined lesion that involves the calcaneofibular ligament. The results compare well with arthrographic and surgical findings.

A review is presented of femtosecond pulse-shaping methods and their application to spectroscopy of atoms, molecules, and condensed materials. Pulse shaping can be used to generate femtosecond pulse sequences and other optical waveforms whose time-dependent amplitude, phase, frequency, and polarization profiles are all specified precisely. The light-matter interaction mechanisms through which such waveforms can be used for optical control over molecular and material responses are discussed. Most of the spectroscopic experiments conducted to date that involve shaped femtosecond waveforms are reviewed. These have involved control over coherent electronic responses of atoms, small molecules, and multiple quantum wells and control over coherent molecular and lattice vibrations. A selective review is presented of theoretical predictions and qualitative discussions of optical control possibilities involving complex ultrafast waveforms.

Actin is a key regulator of RNA polymerase (Pol) II-dependent transcription. Positive transcription elongation factor b (P-TEFb), a Cdk9/cyclin T1 heterodimer, has been reported to play a critical role in transcription elongation. However, the relationship between actin and P-TEFb is still not clear. In this study, actin was found to interact with Cdk9, a catalytic subunit of P-TEFb, in elongation complexes. Using immunofluorescence and immunoprecipitation assays, Cdk9 was found to bind to G-actin through the conserved Thr-186 in the T-loop. Overexpression and in vitro kinase assays showed that G-actin promotes P-TEFb-dependent phosphorylation of the Pol II C-terminal domain. An in vitro transcription experiment revealed that the interaction between G-actin and Cdk9 stimulated Pol II transcription elongation. ChIP and immobilized template assays indicated that actin recruited Cdk9 to a transcriptional template in vivo and in vitro. Using cytokine IL-6-inducible p21 gene expression system, we revealed that actin recruited Cdk9 to endogenous gene. Moreover, overexpression of actin and Cdk9 increased histone H3 acetylation and acetylized histone H3 binding to a transcriptional template through the interaction with histone acetyltransferase, p300. Taken together, our results suggested that actin participates in transcription elongation by recruiting Cdk9 for phosphorylation of the Pol II C-terminal domain, and the actin-Cdk9 interaction promotes chromatin remodeling.

DPP-4 inhibitors are a well-established treatment for type 2 diabetes. They act by improving glycemic control through the incretin system. This class of molecules are well-tolerated and are associated with a low risk of hypoglycemia. Yet, their efficacy in glycemic control is rather moderate and they don't offer a benefit in terms of cardiovascular or renal protection. Even if they have a good safety profile, it is important to pay attention to the risk of cardiac failure and pancreatitis. This article provides an overview of the use of DPP-4 inhibitors in 2020.

Processes leading to enantiomerically pure compounds are of utmost importance, in particular for the pharmaceutical industry. Starting from a racemic mixture, crystallization-induced diastereomeric transformation allows in theory for 100 % transformation of the desired enantiomer. However, this method has the inherent limiting requirement for the organic compound to form a salt. Herein, this limitation is lifted by introducing cocrystallization in the context of thermodynamic deracemization, with the process applied to a model chiral fungicide. We report a new general single thermodynamic deracemization process based on cocrystallization for the deracemization of (R,S)-4,4-dimethyl-1-(4-fluorophenyl)-2-(1H-1,2,4-triazol-1-yl)pentan-3-one. This study demonstrates the feasibility of this novel approach and paves the way to further development of such processes.

There is no consensus about the best systemic treatment for hormonally resistant prostate cancer. Several regimens have been examined; none of them have demonstrated a consistent increase in overall survival. The treatment of hormonally resistant prostate cancer is therefore palliative. Recent studies in Canada have taken the approach that the best way to measure disease palliation is to assess the effects of therapy on disease-related symptoms and quality of life. Studies with mitoxantrone and prednisone confirm that this regimen is well tolerated and leads to symptomatic improvement in approximately 40% of patients, with a median duration of improvement of more than 10 months. This is greater than that achieved with prednisone alone. Treatments that have greater activity against hormonally resistant disease are urgently needed, although improvements probably will be gradual and modest. While it may be appealing to intensity treatments to obtain greater efficacy, there is a real risk that the toxicity will nullify any benefits. This approach of directly measuring the ability of systemic therapies to provide palliation is an appropriate way to assess newer therapies for hormonally resistant prostate cancer.

The prevalence and mechanisms of hypercalcaemia were studied in a series of patients attending a regional referral centre for rheumatic diseases. In a prospective study one case of hypercalcaemia due to primary hyperparathyroidism was found in 251 consecutive patients who were screened over a three month period. In a retrospective study of 39 patients who had been discovered to be hypercalcaemic during the preceding 12 months known cases of hypercalcaemia were found in 38 (97%) cases. Primary hyperparathyroidism was the most common cause (n = 24; 62%), followed by thiazide treatment in five (13%), cancer in three (8%), immobility in three (8%), vitamin D toxicity in two (5%), and chronic liver disease in one (3%). In one case the diagnosis remained unclear after full investigation. This study shows that the causes of hypercalcaemia in rheumatological patients are similar to those in the general population. These observations contrast with previous reports, which suggested that hypercalcaemia may be a complication of rheumatoid arthritis itself.

Similar to northern developed countries, cerebrovascular disease is a leading cause of morbidity and mortality in tropical countries. The epidemiology of stroke in the tropics is different from one tropical region to another and from the tropics to northern latitudes. In tropical regions, stroke is due to the conventional mechanisms encountered in other latitudes, as well as unusual causative mechanisms unique to the tropics. In tropical regions, infectious causes of stroke and nonatherosclerotic mechanisms are more common than in nontropical areas. Our current knowledge of stroke in the tropics is limited by the financial restrictions existing in such regions limiting health care delivery and epidemiological research.

Autopsies are performed much less frequently in the elderly than in younger patients. Little information exists as to causes of death in the institutionalized elderly. The clinical diagnostic error rate documented by autopsy studies ranges from 6% to 68%. We analyzed the clinical and autopsy records of 234 patients who died during a 14 1/2-year period at our chronic care institution to determine the accuracy of clinical cause of death in addition to the pathologic cause of death. The most common causes of death included bronchopneumonia (33%), congestive heart failure (15%), metastatic carcinoma (14%), pulmonary embolism (8%), myocardial infarction (7%), cerebrovascular accident (6%), unknown cause of death (8%), and a miscellaneous group (9%). The highest diagnostic error rate was in the underdiagnosis of pulmonary embolism (39% antemortem accuracy rate). The most accurately diagnosed condition was cerebrovascular accident (92% antemortem accuracy rate). Pneumonia was correctly diagnosed antemortem in 73% of the patients studied. These data suggest that serious and potentially treatable illnesses are underdiagnosed in the elderly institutionalized patient and that there is valuable information to be learned by performing autopsies in the elderly population.

Inhibin B generated by Sertoli cells provides negative feedback on FSH secretion. In men, inhibin B seems to be the physiologically important form of inhibin. Serum inhibin B was measured by two-site immunoenzymatic assay in 40 normal men (27 years of age) with sperm concentrations 100 +/- 9.2 x 10(6)/mL, 51 subfertile men (31 years of age) with sperm concentrations 6.8 +/- 0.8 x 10(6)/mL, 16 men with varicocele with sperm concentrations 54.3 +/- 0.8 x 10(6)/mL (31 years of age), men with hypogonadotrophic hypogonadism, men with Klinefelter syndrome, and men with obstructive and non-obstructive azoospermia. In men with normal sperm concentrations (>20 x 10(6) mL) serum inhibin B was 201 +/- 17 pg/mL and FSH 4 +/- 0.5 IU/L. Varicocele patients showed normal sperm concentrations > 20 x 10(6)/mL, normal serum inhibin B (173 +/- 21 pg/mL), and normal FSH levels (4.6 +/- 0.6 IU/L). In patients with sperm concentrations < 20 x 10(6)/mL the inhibin B level was 118 +/- 14 pg/mL and the FSH level was 10 +/- 1.1 IU/L. In all patients, except those with hypogonadotrophic hypogonadism and Klinefelter syndrome. inhibin B and FSH were inversely correlated (r = -.41, p > 0.01). There was a positive correlation between inhibin B and sperm concentrations (r = .34, p < .01). In varicocele men there was a correlation of r = .574, p < .05. Inhibin B may be a marker of exocrine testicular function and may offer an improved diagnosis of testicular dysfunction.

The synthesis and isolation of an ambient stable perylenediimide radical anion is reported, and its precursor is established as one of the strongest electron acceptors. The radical anion shows absorption up to 1400 nm and is stable in mixed aqueous solution. Interestingly, the radical anion can organize two electron-deficient molecules over its surface to form a π-stacked array. Calculations revealed weak spin polarization via noncovalent interactions. Such interactions are of significance for magnetic exchange and catalysis.

The quinazolinone-containing 2,3-disubstituted piperidines febrifugine and isofebrifugine have been the subject of significant research efforts since their occurrence in Dichroa febrifuga and their anti-malarial actions were first described in the late 1940s. Subsequently they have also been shown to be present in other plants belonging to the hydrangea family and various analogues of febrifugine have been prepared in attempts to tune biological properties. The most notable analogue is termed halofuginone and a substantial body of work now demonstrates that this compound possesses potent human disease relevant activities. This review focuses on the literature associated with efforts dedicated towards uncovering the structures of febrifugine and isofebrifugine, the development of practical methods for their synthesis and the syntheses of structural analogues.

The respiratory burst induced in human eosinophils by serum-treated zymosan (STZ) was found to be almost completely prevented by preincubation of the cells with WEB 2086, an antagonist of platelet-activating factor (PAF). When eosinophils were primed by the addition of 1 mumol/L PAF, subsequent addition of WEB 2086 had only a minor effect on the STZ-induced respiratory burst. These results suggest a role for PAF synthesis and PAF release in the activation of the respiratory burst by STZ. Indeed, supernatant of STZ-stimulated eosinophils was able to prime fresh eosinophils (as did PAF itself), and this effect was again inhibited by WEB 2086. This indicates that eosinophils synthesize and release PAF during STZ stimulation. Measurements of total PAF and PAF release showed that most of the PAF synthesized by eosinophils was released in the extracellular medium. This study shows that synthesis and release of PAF is important for respiratory burst activity induced in human eosinophils by STZ.

Penicillium verrucosum&#160;contaminates temperate cereals with ochratoxin A (OTA) during harvesting and storage. We examined the effect of temperature (25&#160;vs&#160;30&#160;^oC), CO₂&#160;(400&#160;vs&#160;1000 ppm) and matric/solute stress (-2.8&#160;vs&#160;-7.0 MPa) on (i) growth, (ii) key OTA biosynthetic genes and (iii) OTA production on a milled wheat substrate. Growth was generally faster under matric than solute stress at 25&#160;^oC, regardless of CO₂&#160;concentrations. At 30&#160;^oC, growth of&#160;P.&#160;verrucosum&#160;was significantly reduced under solute stress in both CO₂&#160;treatments, with no growth observed at -2.8 MPa (=0.98 water activity, a_w) and 1000 ppm CO₂. Overall, growth patterns under solute stress was slower in elevated CO₂&#160;than under matric stress when compared with existing conditions. The&#160;otapksPV gene expression was increased under elevated CO₂&#160;levels in matric stress treatments. There was fewer effects on the otanrpsPV biosynthetic gene. This pattern was paralleled with the production of OTA under these conditions. This suggest that&#160;P.&#160;verrucosum&#160;is able to actively grow and survive in both soil and on crop debris under three way interacting climate-related abiotic factors. This resilience suggests that they would still be able to pose an OTA contamination risk in temperate cereals post-harvest.

The antifungal activities of many sulfur-containing defense compounds suggest a connection between pathogen infection, primary sulfur metabolism and sulfate nutritional status of plants. This relationship was investigated using Arabidopsis thaliana plants that were cultivated under different sulfur regimes and challenged by Alternaria brassicicola. Plants grown with 500 μM sulfate were significantly less infected compared to plants grown on 50 μM sulfate. Upon infection, the formation of the sulfur-containing defense compound camalexin and the gene expression of the sulfur-rich defense peptide defensin were clearly enhanced in plants grown with an optimal compared to a sufficient sulfate supply in the growth medium. Elevated levels of sulfite and O-acetylserine and cysteine biosynthetic enzymes after infection indicated a stimulation of sulfur metabolism under the higher sulfate supply. The results suggest that, in addition to pathogen-triggered activation of sulfur metabolism and sulfur-containing defense compound formation, the sulfate nutritional status is sensed to contribute to plant defense.

We present a Tc pertechnetate scintigraphy performed in a 64-year-old woman to investigate a mediastinal cystic mass in search of residual gastric mucosa after gastrectomy. She had a history of esophagectomy and gastric pull-up for esophageal cancer. Postoperative leakage necessitated ablation of the gastric pull-up and reconstruction using part of the colon. Oral realimentation resulted in mediastinal pain and brownish discharge within the trachea, raising the suspicion of residual gastric pouch. SPECT/CT demonstrated increased tracer uptake in the median part of the mediastinal cyst, and a biopsy confirmed the presence gastric mucosa.

Although quality of life is difficult to define clearly, a number of instruments and questionnaires have been developed and applied to patients who have amyotrophic lateral sclerosis (ALS). This article reviews the spectrum of quality-of-life questionnaires and instruments used for ALS and the data generated from them. It discusses positive and negative factors that can affect quality of life for the patient and caregiver and concludes with suggestions for ongoing management to enhance quality of life.

Smad7, an inhibitory Smad, acts as a key regulator forming autoinhibitory feedback loop in transforming growth factor-beta (TGF-β) signaling. However, a growing body of evidences suggests that Smad7 is capable of apoptotic function. In the present study, we have demonstrated a proapoptotic function of Smad7 as a negative regulator of survival protein heme oxygenase-1 (HO-1). The HO-1 protein level was elevated in cisplatin-resistant A549 human lung cancer cells and blockade of HO-1 activation sensitized the cells to apoptosis. Interestingly, overexpression of Smad7 decreased HO-1 gene expression and its enzymatic activity. Notably, Smad7 reduced Akt activity and infection with adenovirus expressing a constitutively active form of the Akt reversed the inhibitory effects of Smad7 to HO-1, indicating a negative action mechanism of Smad7 to Akt-HO-1-linked survival pathway. Consistently, Smad7 sensitized A549 cells to cisplatin-induced apoptosis and these effects were dependent on HO-1 and Akt inhibition. Based on these findings, we suggest that targeting Smad7 may be an efficient strategy for overcoming drug-resistance in cancer therapy.

We investigate thermalization dynamics of a driven dipolar many-body quantum system through the stability of discrete time crystalline order. Using periodic driving of electronic spin impurities in diamond, we realize different types of interactions between spins and demonstrate experimentally that the interplay of disorder, driving, and interactions leads to several qualitatively distinct regimes of thermalization. For short driving periods, the observed dynamics are well described by an effective Hamiltonian which sensitively depends on interaction details. For long driving periods, the system becomes susceptible to energy exchange with the driving field and eventually enters a universal thermalizing regime, where the dynamics can be described by interaction-induced dephasing of individual spins. Our analysis reveals important differences between thermalization of long-range Ising and other dipolar spin models.

Topologically nontrivial field excitations, including solitonic, linked, and knotted structures, play important roles in physical systems ranging from classical fluids and liquid crystals, to electromagnetism, classic, and quantum field theories. These excitations can appear spontaneously during symmetry-breaking phase transitions. For example, in cosmological theories, cosmic strings may have formed knotted configurations influencing the Early Universe development, whereas in liquid crystals transient tangled defect lines were observed during isotropic-nematic transitions, eventually relaxing to defect-free states. Knotted and solitonic fields and defects were also obtained using optical manipulation, complex-shaped colloids, and frustrated cholesterics. Here we use confinement of nematic liquid crystal by closed surfaces with varied genus and perpendicular boundary conditions for a robust control of appearance and stability of such field excitations. Theoretical modeling and experiments reveal structure of defect lines as a function of the surface topology and material and geometric parameters, establishing a robust means of controlling solitonic, knotted, linked, and other field excitations.

Although aerogels prepared by the colloidal assembly of nanoparticles are a rapidly emerging class of highly porous and low-density materials, their ambient dried counterparts, namely xerogels, have hardly been explored. Here we report the use of nanoparticle-based BaTiO₃ xerogels as green bodies, which provide a versatile route to ceramic materials under the minimization of organic additives with a significant reduction of the calcination temperature compared to that of conventional powder sintering. The structural changes of the xerogels are investigated during ambient drying by carefully analyzing the microstructure at different drying stages. For this purpose, the shrinkage was arrested by a supercritical drying step under full preservation of the intermediate microstructure, giving unprecedented insight into the structural changes during ambient drying of a nanoparticle-based gel. In a first step, the large macropores shrink because of capillary forces, followed by the collapse of residual mesopores until a dense xerogel is obtained. The whole process is accompanied by a volume shrinkage of 97% and a drop in surface area from 300 to 220 m² g^-1. Finally, the xerogels are sintered, causing another shrinkage of up to 8% with a slight increase in the average pore and crystal sizes. At temperatures higher than 700 &#176;C, an unexpected phase transition to BaTi₂O₅ is observed.

Release of sperm bundles from moth testes is controlled by the local circadian oscillator. The mechanism which restricts migration of sperm bundles to a few hours each day is not understood. We demonstrate that a daily cycle of sperm release is initiated by the migration of folded apyrene sperm bundles through a cellular barrier at the testis base. These bundles have conspicuous concentrations of actin filaments at their proximal end. Inhibition of actin polymerization by cytochalasin at aspecific time of day inhibited sperm release from the testis. Likewise, application of double-stranded actin RNA specifically inhibited sperm release. This RNA-mediated interference (RNAi) lowered the pool of actin mRNA in tissues involved in sperm release. The decline in mRNA levels resulted in the selective depletion of F-actin from the tip of apyrene sperm bundles, suggesting that this actin may be involved in the initiation of sperm release. Combined results of RNAi experiments at physiological, cellular and molecular levels identified unique cells that are critically involved in the mechanism of sperm release.

Granulomatous slack skin (GSS) represents a rare variant of mycosis fungoides, histologically characterized by a variably deep T helper lymphocytes infiltrate with alteration of the dermal elastic tissue and consequent elastolysis, elastophagocytosis and numerous giant cells. Clinically, a development of unelastic, slack skin, especially on flexural areas, is observed. Hereby, we describe a man with a 12-year history of GSS. In 2002, for practical (limitation of movement, deambulation) and cosmetic reasons, he underwent the surgical excision of loose and sagging skinfold over inguinal area, and, afterwards, of the opposite affected inguinal skin. The surgical treatment of bilateral inguinal hernia with reposition of inguinal dislocated vasculature is also reported. In both cases the excised material confirmed the former diagnosis of GSS and revealed a very deep, muscular infiltrate of neoplastic lymphocytes. One year later, a new excision of GSS on the axillae was made. Now, after 2 years, deambulation keeps improving, although an initial relapse of the inguinal slack skin has been observed.

Bone metastasis is a common complication of cancer, and bone is the third most common metastatic site following the lung and liver. Among the various bones, spine is the most common site of metastatic tumors. The treatment goals of patients with spinal metastases are mostly palliative, with the aim of reducing pain and improving quality of life. The treatment of spinal metastases has made significant progress over the past few decades. Each new technology has tried to solve the shortcomings of its predecessors. Currently, there are no mature algorithms or specific techniques that have proven to be the best for spinal metastases, and the treatment method often relies on operator and institutional preferences or biases in some cases. Percutaneous vertebral augmentation has unique value in the management of spinal metastases, understanding its indications, surgical techniques, uses, advantages and complications is critical to providing optimal patient care. We believe that the application of percutaneous vertebral augmentation alone or combined with other techniques can achieve optimal pain relief and functional improvement in the patients with spinal metastases.

This study aims to define cut-off points for the waist:hips girth ratio (WHR), using arterial hypertension as the outcome. The data refer to 3,282 individuals over twenty years of age examined in a survey conducted in the municipality of Rio de Janeiro in 1995-1996, using a two-stage sample. Sixty census tracts were drawn initially; subsequently, 34 households were selected systematically from each tract. Stature, weight, waist and hips girths, and blood pressure were measured in the households. The criterion for hypertension was a systolic blood pressure of ( 140 mmHg or diastolic pressure of ( 90 mmHg, or use of medication to reduce blood pressure. The sensitivity and specificity of different cut-off points for WHR were calculated in the prediction of arterial hypertension according to sex, age, and presence of overweight, classified according to World Health Organization guidelines. The best cut-off points for WHR were 0.95 for men and 0.80 for women. Compared to the waist:stature ratio and waist circumference, the WHR proved more capable of predicting arterial hypertension and less correlated with body mass index.

We (Jamieson and Howk (1992) Int. J. Psychophysiol. 12, 53-61) recently used computer simulations to study factors affecting the correlation between change and initial level (rdx). Four factors were identified: (1), measurement error; (2), floor/ceiling effects (the 'real Law of initial values'); (3), reactivity and (4), skewness. The present study used the same approach to show that a fifth factor, change in variance from pre to post, was also capable of influencing rdx. When the variance increased, rdx became positive; when the variance decreased, rdx became negative. These five factors appear to affect rdx through only two underlying mechanisms: regression to the mean and variance change. The difficulty of separating a 'real Law of initial values' from the other factors is discussed.

Three gymnophallid species in Macoma balthica from the northeastern Pacific Ocean are similar to 3 species in M. balthica from the Baltic Sea. Using light and scanning electron microscopy, we compared the anatomy of the larvae of 2 species of Lacunovermis and of Gymnophallus, and the adults of 2 species of Lacunovermis recovered from incubation on chick allantoic membrane. The third similar pair of Meiogymnophallus multigemmulus and Parvatrema affinis was restudied with light microscopy. Previously described anatomical differences between the 3 pairs of Pacific and Baltic gymnophallids were nullified in this study. Lacunovermis conspicuus Ching, 1965 is synonymized with Lacunovermis macomae (Lebour, 1908), and Gymnophallus gibberosus Loos-Frank, 1971 is synonymized with Gymnophallus somateriae (Levinsen, 1881). Meiogymnophallus multigemmulus Ching, 1965 is synonymized with Parvatrema affinis (Jameson and Nicoll, 1913), becoming M. affinis n. comb.

Despite the recent successes in robotics, artificial intelligence and computer vision, a complete artificial agent necessarily must include active perception. A multitude of ideas and methods for how to accomplish this have already appeared in the past, their broader utility perhaps impeded by insufficient computational power or costly hardware. The history of these ideas, perhaps selective due to our perspectives, is presented with the goal of organizing the past literature and highlighting the seminal contributions. We argue that those contributions are as relevant today as they were decades ago and, with the state of modern computational tools, are poised to find new life in the robotic perception systems of the next decade.

This study tested the mediating effects of violence victimization in the relationship between school climate and adolescent drug use. The hypothesized path model fit data collected from a probability sample of urban high school students (N=586) participating in an evaluation of a violence prevention program funded by the Substance Abuse and Mental Health Services Administration. Findings indicated that the lack of enforcement of school rules and the presence of unsafe places in and around the school influenced adolescent drug use directly and indirectly through their effects on violence victimization.Editors' Strategic Implications: This research confirms the importance of the environment as a contributor to violence victimization. Violence victimization is obviously of concern in its own right, but in addition, these data indicate that it also contributes to adolescent drug use. School administrators should be aware that unsafe places in schools and the failure to enforce school rules may affect such victimization and drug use.

In transmissible spongiform encephalopathies (TSE), the endogenous protease-sensitive prion protein (PrP-sen) of the host is converted to a pathologic form (PrP-res) that has greatly enhanced proteinase K resistance, insolubility, and beta sheet content. To investigate the possibility that alterations at aspartyl or asparaginyl residues in the form of D-aspartate and/or L-isoaspartate could play a role in either the formation or stabilization of PrP-res in TSE-infected animals, we assayed for the presence of these abnormal residues in PrP-res. Protein D-aspartyl/L-isoaspartyl carboxyl methyltransferase (PIMT) was used to methylate and radiolabel altered aspartyl residues, which were detected in PrP-res, but at low levels (0.5 mole%). The scarcity of D-aspartyl and/or L-isoaspartyl groups in PrP-res suggests that this modification is unlikely to be primarily responsible for the differences between PrP-res and PrP-sen. However, it remains possible that such modifications in substoichiometric numbers of PrP molecules could help to initiate the PrP-res formation or stabilize PrP-res polymers in vivo.

Subarachnoid hemorrhage following severe trauma to the head is relatively common. In most cases the bleed originates from superficial veins and occasionally from arteries. Following the replacement of cerebral angiography with CT in the diagnostic evaluation of head traumas fewer traumatic aneurysms have been observed. This may indicate that some traumatic aneurysms are missed if angiographic procedures are not performed in patients with severe head injury. Trauma patients admitted to our institution are submitted to CT including a bone algorithm. In case of subarachnoid hemorrhage, especially in the basal cisterns, CT-angiography is performed. Digital subtraction angiography is performed as well in cases with uncertain interpretations. During one year 81 patients were admitted with subarachnoid hemorrhage following head trauma. Thirteen (16%) of them underwent CTangiography and in five (6.2%) with SAH in the basal cistern traumatic aneurysms were found. Four of these cases had a skull base fracture including fractures through the clivus. Four cases were embolized and one very small extradural aneurysm is still not treated. One small pericallosal aneurysm was operated. A traumatic aneurysm should always be suspected n patients with skull base fractures and subarachnoid hemorrhage in the basal cisterns.

Paraoxonase 1 (PON1) hydrolyzes a number of toxic organophosphorous compounds and reduces lipid peroxide accumulation, and PON1 genetic polymorphisms in the coding region modulate serum PON1 activity. In this study, we investigated the association between 3 polymorphisms of PON1 located in intron 5 (17899insdelTT and 17974CT) and exon 6 (192QR) and serum PON1 activity. The genetic polymorphisms and serum activity of PON1 were analyzed in 153 healthy Koreans by using a direct sequencing assay and spectrophotometric method, respectively. A significant linkage disequilibrium (LD) was observed between all tested single nucleotide polymorphisms, with the strongest LD observed between 17899insdelTT and 192QR (D' = 0.984). The 17899insdelTT, 17974CT and 192QR genetic polymorphisms were associated with significant differences in serum paraoxonase activity. In multiple regression analyses, smoking, triglyceride level, high-density lipoprotein (HDL) level, and the 17899insdelTT and 192QR genetic polymorphisms were significant determinants of serum paraoxonase activity, while age, smoking, triglyceride level, HDL level, and the 192QR genetic polymorphism were significant determinants of serum arylesterase activity. These results suggest that although the 192QR genetic polymorphism in the coding region of PON1 is primarily associated with serum PON1 activity, the intronic polymorphisms are also involved in serum PON1 activity, and this association may be mediated by LD.

Statutes, regulations, and litigation are pivotal tools for creating conditions for people to lead healthier and safer lives. Law can educate, create incentives, and deter; mandate safer product design and use of property; and alter the informational, physical, or economic environment. This article defines public health law as the power and duty of the state to ensure conditions for people to be healthy and limitations on the state's power to constrain autonomy, privacy, liberty, and proprietary interests of individuals and businesses. The 5 essential characteristics of public health law discussed are (1) the government's responsibility to defend against health risks and promote the public's health; (2) the population-based perspective of public health, emphasizing prevention; (3) the relationship between government and the populace; (4) the mission, core functions, and services of the public health system; and (5) the power to coerce individuals, professionals, and businesses for the community's protection. JAMA. 2000;283:2837-2841

The effects of 13 soybean varieties (356, M4, M7, M9, Clark, Sahar, JK, BP, Williams, L17, Zane, Gorgan3, and DPX) on nutritional indices of the cotton bollworm, Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae), were determined at 25 ± 1° C, 65 ± 5% RH and a photoperiod of 16:8 L:D. Fourth instar larvae reared on Zane showed the highest efficiency of conversion of digested food (ECD) and approximate digestibility (AD) values (0.299 and 0.867, respectively) compared with other varieties. The lowest value of ECD and food consumed (FC) was on 356 (0.133 and 53.82 mg, respectively). The highest and lowest efficiency of conversion of ingested food (ECI) of fifth instar larvae (0.235 and 0.156, respectively) were on Zane and M4, respectively. The ECI and ECD values of whole larval instars were the highest on M7 (0.524 and 0.820, respectively) and lowest on Sahar (0.279 and 0.353, respectively). However, the highest and lowest value of consumption index (CI) was on M7 (7.351) and BP (3.462). Among the different varieties of soybean, the highest AD value was on M9 (0.858), and the lowest was on Zane (0.597). The results indicated that M4, Sahar, and JK were partially resistant to H. armigera.

Exotic hierarchical rutile TiO2 nanostructures are synthesized by surfactant free single step hydrothermal route. The effect of reaction temperature, ranging from 140°C to 200°C on the properties of the synthesized rutile-TiO2 is investigated. The synthesized rutile-TiO2 nanostructures are characterized using X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy, UV-vis spectroscopy and scanning electron microscopy techniques. The deposited TiO2 samples are found to be photoelectrochemically active and the best photoelectrochemical performance (0.95±0.05%) is obtained for the sample deposited at 180°C. A possible temperature dependent growth mechanism resulting in photochemically active TiO2 nanostructure thin films is proposed.

This paper discusses the issues of radiation exposure that especially occur on the Doppler Orbitography and Radiopositioning Integrated on Satellite (DORIS) ultrastable oscillator (USO) that has been placed on the Jason-2 oceanography mission as the reference clock. We have studied the frequency response of the Jason-2 USO (launched in June 2008, at 66&#176; of inclination and 1336 km of altitude) over 8.5 years. This is the only mission that provides different sources of data, internal and external, which permit a precise description of the oscillator behavior using several assumptions. While the ICARE-NG instrument provided continuous measurement of the electron and the proton fluxes, the Time Transfer by Laser Link (T2L2) experiment demonstrated its ability to monitor the "reading" of the oscillator at a level of a few parts in 10^-13 with respect to a ground network of laser stations equipped with atomic clocks. From these inputs, and also environmental parameters such as the orbit, the attitude law of the platform, and the temperature of the oscillator, we have developed a complete physical model of the DORIS USO that fits the data at less than slightly below the threshold of 10^-12 that limits the use of the DORIS data in current space geodesy analyses. In this way, the model also makes it possible to provide an assessment of the new Jason-3 USO to radiation effects after the satellite launch in January 2016.

The addition of 2 mM sodium butyrate to monolayers enhances differentiation of Ishikawa endometrial cells. Cells from this cell line have been shown to enlarge and lift off the dish into dome structures over a period of 24-48 h in response to a factor in fetal bovine serum (FBS) [Fleming, 1995 J Cell Biochem in press]. When butyrate is added to monolayers, together with FBS, three- to fourfold higher numbers of differentiated structures, domes and predomes, can be counted. It had previously been shown [Holinka et al., 1986b] that estradiol induces heat stable placental alkaline phosphatase in Ishikawa cells. The addition of butyrate, on the other hand, results in a significant increase in levels of a heat labile alkaline phosphatase isozyme. The heat labile isozyme is also increased to some extent in cells stimulated to differentiate in response to FBS in the absence of butyrate. Differential inhibition by homoarginine and phenylalanine indicates that butyrate is inducing the liver-bone kidney isozyme that is found in endometrial glands in vivo.

A simple and rapid reversed-phase high-performance liquid chromatographic method has been developed for the separation and simultaneous determination of related substances of mirtazapine in bulk drugs and pharmaceutical formulations. Six impurities, including one degradation product of mirtazapine, have been separated on a BDS Hypersil (4.6 x 250 mm; particle size 5 microm) column with a mobile phase consisting of 0.3% triethylamine (pH 3.0)-acetonitrile (78:22 v/v) eluted in an isocratic mode and monitored with a photo diode array detector at 215 nm. The chromatographic behavior of all the analytes was studied under variable compositions of different solvent systems, temperatures, buffer concentrations, and pH values. The method was validated in terms of accuracy, precision, and linearity. The inter- and intra-day assay precision was found to be < 0.98% [relative standard deviation; (RSD)] and the recoveries were in the range 95.54-102.22% with RSD < 2.21%. The correlation coefficients for calibration curves for mirtazapine as well as impurities were in the range of 0.9941-0.9999. The method was successfully applied to the analysis of commercial formulations and the recoveries of mirtazapine were in the range of 99.38-100.73% with < 0.52% RSD. The method is useful not only for rapid evaluation of the purity of mirtazapine, but also for the simultaneous determination of related substances in bulk drugs and pharmaceutical formulations.

Glaucoma is one of the most common causes of irreversible vision loss worldwide. It is an insidious disease with a multifactorial pathogenesis. Despite progress in treatment methods, prevention and lifestyle modifications may be useful in slowing the progression of this disease. This systematic review aimed to evaluate the influence of diet, oxidative stress, and disturbances in blood serum levels of nutrients on the incidence and severity of glaucoma based on scientific reports on the role of nutrition in the pathogenesis and course of glaucoma. This paper presents an analysis of the above issues; however, further research is required to develop this topic. Future clinical trials are needed to assess the influence of nutrition and to develop nutritional management strategies for patients with glaucoma.

Health Impact Assessments (HIAs) have quickly become a widely utilized tool for integrating health and health-related evidence and data into decision making processes across a range of projects and polices. Integrating and utilizing the wide range of available data can be daunting. To support communities seeking to engage in health impact assessments, we developed the Neighborhood Potential Health Impact Score (NPHIS) methodology. We present the NPHIS method's four step process, and how this process was applied to an HIA focusing on the rebuilding of public housing following a natural disaster. We discuss developing the boundary definition, selection and definition of indicators, calculation of the NPHIS, and interpretation and utilization of the scores. Findings were validated using feedback from a community stakeholder advisory board as well as through feedback collected from focus groups of community residents. NPHIS methodology has proven to be a useful resource in better understanding the complex sources of potential health impacts facing communities, and in being an evidence-based, data-driven resource for HIA decision-makers and their stakeholders in our specific application. Other groups seeking to integrate similar data into their decision-making processes could benefit from replicating the NPHIS in their efforts.

Sediments collected in Tiber river and in its main tributary water courses within the urban area of Rome were tested for mutagenicity by means of Vicia faba root tips micronucleus (MN) test. Representative samples were scored for micronucleus generating events (chromosome/chromatid loss and fragments) too. Sediments were assayed for content of the thirteen most important chemicals of polycyclic aromatic hydrocarbon (PAH) group and for some heavy metal ions (Cd, Cr, Cu, Ni, Pb, Zn). Samples were collected in four tributary rivers (Prima Porta, Acqua Traversa, Aniene and Magliana) just before their confluence with Tiber river and at different stations along the Tiber river itself upstream and downstream the sites of confluence of the sampled tributaries. All samples were collected in July 1992. An alarming level of mutagenicity was reached in most of the tested stations, with an effect comparable to an X-rays exposure up to 0.4 Gy. Chemical analysis showed that the total amount of identified PAHs ranged from 4.5 to 625.2 ng/g of dry matrix in the different stations and the total amount of heavy metals ranged from 130 to 570 ppm. Tiber mutagenicity is likely to be mainly due to local factors such as the confluence of a small polluted tributary rather than to large scale effect due to an upstream-downstream relationship.

Cryopreserved peripheral blood stem cell (PBSC) products can induce a number of infusion-related adverse reactions, including life-threatening cardiac, neurologic, and other end-organ complications. Preliminary analyses suggested limiting the daily total nucleated cell dose infused might decrease the incidence of these adverse effects. A policy change implemented in December 2007, limiting the total nucleated cell (TNC) dose to <1.63 × 10(9) TNC/kg/day, allowed us to assess the impact of this intervention on infusion-related safety, infusion schedules, engraftment, and costs in cohorts of patients undergoing autologous stem cell transplants (ASCTs) 2 years before (325 ASCTs in 288 patients) and 2 years after the policy change (519 ASCTs in 479 patients). The percentage of autologous transplant patients requiring multiple day infusions increased from 6% to 24%. Concurrently, the incidence of infusion-related grade 3-5 severe infusion-related adverse events (SAEs) decreased significantly, from 4% (13 of 325) prepolicy change to 0.6% (3 of 519) postpolicy change (P < .0004). Multiday infusions were not associated with increased time to neutrophil or platelet engraftment or the costs of transplantation. We conclude that limiting the daily TNC dose improved the safety of this procedure without compromising engraftment or increasing the costs of the procedure.

Boronic acids and boronate esters find appreciable use in chemical biology. Molecules containing orthogonal boronic acid pairs can be utilized for sequential metal-catalyzed cross-couplings for facile preparation of complex bioconjugates including protein-protein conjugates. In this paper, we expand bis-boronic acid reagents for tandem covalent and dynamic bioconjugation. Sequential cross-coupling of 2-nitroarylboronic acid with cysteine residues and condensation of phenylboronic acid with salicylhydroxamic acids (SHA) readily afforded bioconjugates under physiological conditions with dual covalent and dynamic linkages. Both small molecule- and macromolecule-protein conjugates were amenable with this approach and reversible upon addition of excess unfunctionalized SHA or reactive oxygen species. These investigations provide new insights into the kinetic stability of SHA adducts.