Precise length measurements in multimode optical fibers.
Selective optical excitation permits both the group index and the group delay of on-axis modes of multimode fibers to be determined with high precision. The group index of several types of fiber was measured at 1310 nm in a fiber Michelson interferometer, and the values were tabulated. Group delays were obtained from the transit time of short-duration optical pulses. From these data the length of reference fibers approximately 2 km long was calculated. Length-measurement accuracy was limited by group-index uncertainties to approximately 0.04%. Also, a technique that uses these reference fibers to minimize uncertainties in distance measurements made with multimode optical-time-domain reflectometers is described.


Central nervous system damage, monocytes and macrophages, and neurological disorders in AIDS.
This review focuses on the role of the extended macrophage/monocyte family in the central nervous system during HIV or SIV infection. The accumulated data, buttressed by recent experimental results, suggest that these cells play a central, pathogenic role in retroviral-associated CNS disease. While the immune system is able to combat the underlying retroviral infection, the accumulation and widespread activation of macrophages, microglia, and perivascular cells in the CNS are held in check. However, with the collapse of the immune system and the disappearance of the CD4(+) T cell population, productive infection reemerges, especially in CNS macrophages. These cells, as well as noninfected macrophages, are stimulated to high levels of activation. When members of this cell group become highly activated, they elaborate a wide spectrum of deleterious substances into the neural parenchyma. In the final phases of HIV or SIV infection, this chronic, widespread, and dramatic level of macrophage/monocyte/microglial activation constitutes a self-sustaining state of macrophage dysregulation, which results in pathological alterations and the emergence of various neurological problems.


Inverse relationship between GLUT-4 phosphorylation and its intrinsic activity.
In this study, we examined the effect of phosphorylation on GLUT-4 function in isolated rat adipocytes. Adipocytes labeled with 32P for 2 h were incubated with parathyroid hormone (PTH) (20 ng/ml) for 60 min and then exposed to insulin (25 ng/ml) for an additional 30 min. 32P-GLUT-4 was immunoprecipitated from the plasma membrane and low density microsomal fractions, and its degree of phosphorylation was determined by autoradiography and densitometry. Results were expressed as 32P-GLUT-4 specific activity (phosphorylation/unit of protein). GLUT-4 intrinsic activity was measured using [14C]2-deoxyglucose uptake in plasma membrane vesicles. PTH significantly increased GLUT-4 phosphorylation and eliminated the insulin-stimulated dephosphorylation of GLUT-4. Western blotting revealed normal distribution of GLUT-4 before and after insulin stimulation in control and PTH-treated cells, suggesting that phosphorylation of GLUT-4 does not interfere with its recruitment to the plasma membrane. In contrast, intrinsic activity of phosphorylated GLUT-4 was significantly reduced (p < 0.01). Preincubation of adipocytes with calcium channel blocker (nitrendipine) and cyclic AMP antagonist (RpcAMP) restored GLUT-4 intrinsic activity in the PTH-treated cells. In several experiments, GLUT-4 was phosphorylated in vitro in plasma membrane vesicles isolated from normal adipocytes exposed to insulin. This in vitro phosphorylation reduced GLUT-4 intrinsic activity by approximately 35% (p < 0.01). We conclude that phosphorylation of GLUT-4 significantly impairs the ability of insulin to stimulate its intrinsic activity.


Older adults' acceptance of psychological, pharmacological, and combination treatments for geriatric depression.
We examined older adults' ratings of the acceptability of geriatric depression treatments. We presented 120 community-dwelling participants with vignettes describing an older adult experiencing either mild to moderate or severe depression. Participants rated the acceptability of three different treatments: cognitive therapy (CT), antidepressant medication (AM), and a combination treatment of CT and AM (COM). For general acceptability, participants rated COM as a more acceptable treatment for depression than both CT and AM. With respect to perceived negative aspects of treatments, they rated CT as a more acceptable treatment for mild to moderate depression than both AM and COM. Participants rated both COM and CT as more acceptable treatments for severe depression than AM. Results indicate that combining psychotherapy and AM may be viewed as most acceptable by community-dwelling, nondepressed older adults.


DNA adenine adducts induced by nitrogen mustards and their role in transcription termination in vitro.
Previous studies have demonstrated that three cancer chemotherapeutic compounds of the nitrogen mustard class, melphalan (L-PAM), nitrogen mustard (HN2) and chlorambucil (CBC), each generated DNA lesions that prematurely terminate in vitro transcription. Sites of these lesions were inconsistent with sites of N7 guanine monoadducts formed by these compounds, and in the cases of L-PAM and CBC were suggestive of adenine lesions. The present study is an attempt to identify and characterize nitrogen mustard-induced non-N7 guanine DNA adducts, and in particular adenine DNA adducts, and to assess their role in drug-induced in vitro transcription termination. Data from studies using a modified Maxam-Gilbert DNA sequencing technique demonstrate that L-PAM and CBC, but not HN2, generate heat-labile, alkaline-stabilized adenine adducts at nearly every adenine in a region of a defined DNA template examined. Comparison of sites of L-PAM- and CBC-induced adenine adducts to known sites of drug-induced transcription termination in the same DNA template show that L-PAM- and CBC-induced transcription termination is associated not with drug lesions at single adenines, but rather with drug-induced adducts at neighboring adenines. Additional in vitro transcription studies using a small DNA molecule generated by polymerase chain reaction-mediated DNA amplification demonstrate that none of the transcription-terminating lesions induced by L-PAM and CBC in this molecule are interstrand in nature. These results suggest that some, but not all, nitrogen mustard compounds can generate heat-labile adenine lesions in DNA, and that bifunctional nitrogen mustards that can form heat-labile adenine adducts also form adducts consistent with intrastrand adenine-adenine crosslinks. These adducts at pairs of adenines in turn appear to be responsible for L-PAM- and CBC-induced transcription termination in vitro.


Perioperative care of patients with epidermolysis bullosa: proceedings of the 5th international symposium on epidermolysis bullosa, Santiago Chile, December 4-6, 2008.
Epidermolysis bullosa (EB) has become recognized as a multisystem disorder that poses a number of pre-, intra-, and postoperative challenges. While anesthesiologists have long appreciated the potential difficult intubation in patients with EB, other systems can be affected by this disorder. Hematologic, cardiac, skeletal, gastrointestinal, nutritional, and metabolic deficiencies are foci of preoperative medical care, in addition to the airway concerns. Therefore, multidisciplinary planning for operative care is imperative. A multinational, interdisciplinary panel of experts assembled in Santiagio, Chile to review the best practices for perioperative care of patients with EB. This paper presents guidelines that represent a synthesis of evidence-based approaches and the expert consensus of this panel and are intended to aid physicians new to caring for patients with EB when operative management is indicated. With proper medical optimization and attention to detail in the operating room, patients with EB can have an uneventful perioperative course.


Evolved Bmp6 enhancer alleles drive spatial shifts in gene expression during tooth development in sticklebacks.
Mutations in enhancers have been shown to often underlie natural variation but the evolved differences in enhancer activity can be difficult to identify in vivo. Threespine sticklebacks (Gasterosteus aculeatus) are a robust system for studying enhancer evolution due to abundant natural genetic variation, a diversity of evolved phenotypes between ancestral marine and derived freshwater forms, and the tractability of transgenic techniques. Previous work identified a series of polymorphisms within an intronic enhancer of the Bone morphogenetic protein 6 (Bmp6) gene that are associated with evolved tooth gain, a derived increase in freshwater tooth number that arises late in development. Here, we use a bicistronic reporter construct containing a genetic insulator and a pair of reciprocal two-color transgenic reporter lines to compare enhancer activity of marine and freshwater alleles of this enhancer. In older fish, the two alleles drive partially overlapping expression in both mesenchyme and epithelium of developing teeth, but the freshwater enhancer drives a reduced mesenchymal domain and a larger epithelial domain relative to the marine enhancer. In younger fish, these spatial shifts in enhancer activity are less pronounced. Comparing Bmp6 expression by in situ hybridization in developing teeth of marine and freshwater fish reveals similar evolved spatial shifts in gene expression. Together, these data support a model in which the polymorphisms within this enhancer underlie evolved tooth gain by shifting the spatial expression of Bmp6 during tooth development, and provide a general strategy to identify spatial differences in enhancer activity in vivo.


Cellular mRNA expressions of anti-oxidant factors in the blood of preeclamptic women.
To assess the alterations of mRNA expressions associated with oxidative stress in the cellular component of blood from pregnant women with pre-eclampsia. Peripheral blood samples were obtained from pregnant women with and without pre-eclampsia. Cellular RNA was subjected to a reverse transcription polymerase chain reaction (PCR) assay in order to examine the mRNA distribution among women with pre-eclampsia (n = 24) and control subjects (n = 24) during 35-41 weeks of gestation. The data were analyzed by non-parametric statistics. Significant differences between the pre-eclampsia subjects and the controls were observed in the gene expressions associated with oxidative stress. Lower values in the pre-eclampsia group were found for heme oxygenase (HO)-1, HO-2, catalase and superoxide dismutase (SOD). The HO-1, HO-2 and the catalase levels significantly correlated with proteinuria, and the HO-2 level with systolic blood pressure. Significantly lower concentrations of HO-1, HO-2, SOD and catalase are found in the cellular component of blood from pre-eclamptic patients. The values correlate with the severity of pre-eclampsia. These findings indicate that enhanced oxidative stress and a decrease in the number of anti-oxidant enzymes may be associated with pre-eclampsia.


Preparation and Characterization of Hydrophobically Grafted Starches by In Situ Solid Phase Polymerization.
Three kinds of hydrophobic groups grafted starches of maleic anhydride grafted starch (MAH-g-starch), lactic acid grafted starch (LA-g-starch), and methyl acrylate grafted starch (MA-g-starch) were prepared by in situ solid phase polymerization. The results of Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) confirmed successful grafting. The grafting ratios of MAH-g-starch, LA-g-starch, and MA-g-starch were 6.50%, 12.45%, and 0.57%, respectively. Influenced by the grafting ratio, LA-g-starch had the best relative hydrophobicity and the largest molecular weight, and those for MA-g-starch were the worst. The surfaces of grafted starches were covered with graft polymer, with obvious surface roughness and bond degree of MAH-g-starch and LA-g-starch. The crystalline structure of grafted starches showed some damage, with LA-g-starch exhibiting the greatest decrease in crystallinity, and less of a change for MA-g-starch. Overall, the grafting reaction improved thermoplasticity, with LA-g-starch the most improved, followed by MAH-g-starch, and then MA-g-starch.


Comparative effects of ethylene and cyanide on respiration, polysome prevalence, and gene expression in carrot roots.
Treatment of carrot roots (Daucus carota L.) with 10 microliters per liter ethylene in O(2) evokes a three- to four-fold increase in polysome prevalence and associated poly(A)(+) RNA. The increase in polysome prevalence is attended by a similar change in CO(2) evolution. The increase in polysomal poly(A)(+) mRNA constitutes primarily a generic increase in constitutive mRNAs as assayed by in vitro translation. However, changes in the relative abundance of several in vitro translatable ethylene specific mRNAs do occur.Cyanide, at concentrations which inhibit cytochrome oxidase, initiates a respiratory rise very similar in kinetics and magnitude to that evoked by ethylene. Moreover, the combined treatment with cyanide and ethylene evokes a respiratory response resembling that caused by ethylene or cyanide alone. Nevertheless, cyanide, in the presence of ethylene, significantly inhibits the increase in polysome prevalence and new gene expression associated with ethylene treatment of carrot roots. Separation of in vitro translation products by one-dimensional and two-dimensional gel electrophoresis shows that several new in vitro translation products appear in cyanide-treated carrots different from those evoked by ethylene. Engagement of the less energy efficient alternative electron transport path by cyanide may be responsible for inhibition of the normal ethylene associated increase in polysome prevalence and new gene expression. The implications of these results on regulation of respiratory metabolism are discussed and compared with the results for similar experiments with avocado fruit (Tucker and Laties 1984 Plant Physiol 74: 307-315) in which cyanide does not inhibit an ethylene educed increase in polysome prevalence and change in gene expression.


Delayed toxicity of cyclophosphamide on the bladder of DBA/2 and C57BL/6 female mouse.
The present study describes the delayed development of a severe bladder pathology in a susceptible strain of mice (DBA/2) but not in a resistant strain (C57BL/6) when both were treated with a single 300 mg/kg dose of cyclophosphamide (CY). Inbred DBA/2 and C57BL/6 female mice were injected with CY, and the effect of the drug on the bladder was assessed during 100 days by light microscopy using different staining procedures, and after 30 days by conventional electron microscopy. Early CY toxicity caused a typical haemorrhagic cystitis in both strains that was completely repaired in about 7-10 days. After 30 days of CY injection ulcerous and non-ulcerous forms of chronic cystitis appeared in 86% of DBA/2 mice but only in 4% of C57BL/6 mice. Delayed cystitis was characterized by infiltration and transepithelial passage into the lumen of inflammatory cells and by frequent exfoliation of the urothelium. Mast cells appeared in the connective and muscular layers of the bladder at a much higher number in DBA/2 mice than in C57BL/6 mice or untreated controls. Electron microscopy disclosed the absence of the typical discoidal vesicles normally present in the cytoplasm of surface cells. Instead, numerous abnormal vesicles containing one or several dark granules were observed in the cytoplasm of cells from all the epithelial layers. Delayed cystitis still persisted in DBA/2 mice 100 days after treatment. These results indicate that delayed toxicity of CY in female DBA/2 mice causes a bladder pathology that is not observed in C57BL/6 mice. This pathology resembles interstitial cystitis in humans and could perhaps be used as an animal model for studies on the disease.


Sydney Melancholia Prototype Index (SMPI): translation and cross-cultural adaptation to Brazilian Portuguese.
Depression is possibly not a single syndrome but rather comprises several subtypes. DSM-5 proposes a melancholia specifier with phenotypic characteristics that could be associated with clinical progression, biological markers or therapeutic response. The Sydney Melancholia Prototype Index (SMPI) is a prototypic scale aimed to improve the diagnosis of melancholia. So far, there is only an English version of the instrument available. The aim of this study is to describe the translation and adaptation of the English version of the SMPI into Brazilian Portuguese. Translation and cross-cultural adaptation of the self-report (SMPI-SR) and clinician-rated (SMPI-CR) versions into Brazilian Portuguese were done following recommendations of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). This guideline includes the following steps: preparation, forward translation, reconciliation, back translation, back translation review, harmonization, cognitive debriefing, debriefing results review, proofreading and final report. The Brazilian Portuguese versions of the SMPI were well-accepted by respondents. Changes in about two-thirds of the items were considered necessary to obtain the final Brazilian Portuguese version of the SMPI. Both versions of the SMPI are now available in Brazilian Portuguese. The instrument could become an important option to enhance studies on melancholia in Portuguese-speaking samples.


Pathologic Features of the Intervertebral Disc in Young Nova Scotia Duck Tolling Retrievers Confirms Chondrodystrophy Degenerative Phenotype Associated With Genotype.
Chondrodystrophy results in predictable and progressive biochemical and structural changes to the intervertebral disc, resulting in early onset degeneration and dystrophic mineralization of the disc. Accelerated degeneration and mineralization of the intervertebral disc are common in multiple dog breeds and can result in compromised function, herniation, pain, and a variety of neurological sequelae. A mutation responsible for chondrodystrophy in dogs has been identified as an aberrant fibroblast growth factor 4 (FGF4) retrogene insertion on chromosome 12 (CFA12) and is associated with short stature of the Nova Scotia Duck Tolling Retriever. Segregation of the CFA12 FGF4 retrogene in this dog breed provides an opportunity to examine the effect of retrogene presence on radiographic and histologic appearance of chondrodystrophic disc degeneration within a single breed. Here we found that in the intervertebral discs isolated from 2 dogs with the CFA12 FGF4 genotype, the nucleus pulposus was largely replaced by cartilaginous tissue, and physaliferous notochordal cells were rarely if ever identified. These findings are in contrast to the normal histologic findings in 2 breed-matched dogs lacking the mutation. The findings are consistent with premature chondroid degeneration of the intervertebral disc and suggest that the presence of the CFA12 FGF4 retrogene is sufficient to cause the chondrodystrophic phenotype.


A self-associating protein critical for chromosome attachment, division, and polar organization in caulobacter.
Cell polarization is an integral part of many unrelated bacterial processes. How intrinsic cell polarization is achieved is poorly understood. Here, we provide evidence that Caulobacter crescentus uses a multimeric pole-organizing factor (PopZ) that serves as a hub to concurrently achieve several polarizing functions. During chromosome segregation, polar PopZ captures the ParB*ori complex and thereby anchors sister chromosomes at opposite poles. This step is essential for stabilizing bipolar gradients of a cell division inhibitor and setting up division near midcell. PopZ also affects polar stalk morphogenesis and mediates the polar localization of the morphogenetic and cell cycle signaling proteins CckA and DivJ. Polar accumulation of PopZ, which is central to its polarizing activity, can be achieved independently of division and does not appear to be dictated by the pole curvature. Instead, evidence suggests that localization of PopZ largely relies on PopZ multimerization in chromosome-free regions, consistent with a self-organizing mechanism.


A tyrosine kinase signaling pathway accounts for the majority of phosphatidylinositol 3,4,5-trisphosphate formation in chemoattractant-stimulated human neutrophils.
The signaling pathway leading from G protein-coupled chemoattractant receptors to the generation of oxidants by NADPH oxidase in human neutrophils requires the formation of the lipid mediator phosphatidylinositol 3,4,5-trisphosphate (PIP3). Two mechanisms through which PIP3 can be generated have been described in human leukocytes. One pathway involves the coupling of the src-related tyrosine kinase Lyn to the "classical" p85/p110 form of phosphatidylinositol 3-kinase. The second paradigm utilizes a novel form of phosphatidylinositol 3-kinase whose activity is directly regulated by G protein betagamma subunits. In this paper, we show that formation of PIP3 in chemoattractant-stimulated neutrophils is substantially attenuated by inhibitors that specifically block tyrosine kinase activity. These data suggest that the Lyn activation pathway plays a major role in the formation of this important lipid messenger during chemoattractant stimulation of human neutrophils.


[Effect of Spearmint oil on inflammation, oxidative alteration and Nrf2 expression in lung tissue of COPD rats].
To investigate the effect of Spearmint oil on inflammation, oxidative alteration and Nrf2 expression in rats with chronic obstructive pulmonary disease(COPD). COPD model was induced by intratracheal instillation of Klebsiella pneumonia and lipopolysaccharide (LPS) for 12 weeks in rats, and COPD rats were treated with Spearmint oil for 3 weeks. After COPD was induced, the pathological changes, changes in leucocyte number in blood and bronchoalveolar lavage fluid (BALF), MDA in lung homogenate and Nrf2 expression were observed. The effects of Spearmint oil on these changes were determined. Spearmint oil 100 mg*kg(-1)significantly reduced leucocyte numbers in BALF, and attenuated bronchiolitis, pulmonary interstitial inflammation and inflammation cell infiltration. Spearmint oil 30-300 mg*kg(-1)decreased the destruction of pulmonary alveolus and the thickness of bronchioles walls, and inhibited goblet cell proliferation. Spearmint oil significantly reduced MDA in lung homogenate, and decreased the expression of Nrf2 protein in lung tissues. Spearmint oil has protective effect on lung injury in COPD rats, since it improves pulmonary inflammation,oxidative alteration, and enhances Nrf2 protein expression.


[Bartter's syndrome: variability and clinical course].
The clinical, hydroelectrolytical and hormonal features, as well as the treatment of 3 patients with Bartter's syndrome are analyzed. The patients consulted due to severe hypokalaemia with little clinical expression (paresthesiae, carpopedal spasms, polyuria, polydipsia and/or weakness). All had normal blood pressure, hypokalemia, hyperreninaemic hyperaldosteronism and a decrease in the fractional distal chloride reabsorption; hyperuricaemia was observed in two cases and hypomagnesemia in one. Treatment with oral potassium supplements and indomethacin managed to raise serum K to around the lower limit of the normal range. However, the tubular defect and hyperreninaemic hyperaldosteronism persisted. The urinary excretion of prostaglandin E2 was normal in both the patients in whom it was measured. Given the minimal clinical expression of hypokalemia despite the difficulty in correcting it, it is probable that this syndrome often remains unrecognized.


Towards Profiles of Resistance Development and Toxicity for the Small Cationic Hexapeptide RWRWRW-NH2.
RWRWRW-NH2 (MP196) is an amphipathic hexapeptide that targets the bacterial cytoplasmic membrane and inhibits cellular respiration and cell wall synthesis. In previous studies it showed promising activity against Gram-positive bacteria and no significant cytotoxicity or hemolysis. MP196 is therefore used as lead structure for developing more potent antibiotic derivatives. Here we present a more comprehensive study on the parent peptide MP196 with regard to clinically relevant parameters. We found that MP196 acts rapidly bactericidal killing 97% of initial CFU within 10 min at two times MIC. We were unable to detect resistance in standard 24 and 48 h resistance frequency assays. However, MP196 was effective against some but not all MRSA and VISA strains. Serum binding of MP196 was intermediate and we confirmed its low toxicity against mammalian cell lines. MP196 did neither induce NFκB activation nor cause an increase in IL8 levels at 250 μg/mL, and no IgE-dependent activation of basophil granulocytes was detected at 500 μg/mL. Yet, MP196 demonstrated acute toxicity in mice upon injection into the blood stream. Phase contrast microscopy of mouse blood treated with MP196 revealed a shrinking of erythrocytes at 250 μg/mL and severe morphological changes and lysis of erythrocytes at 500 μg/mL. These data suggest that MP196 derivatization directed at further lowering hemolysis could be instrumental in overcoming acute toxicity. The assessment of hemolysis is a critical step in the evaluation of the clinical potential of promising antimicrobial peptides and should be accompanied by microscopy-based morphological analysis of blood cells.


Management of massive air leak following intubation injury in a very low birth weight infant.
Perforation of an infant's trachea after orotracheal intubation for general anaesthesia is a rarely described serious complication. This article reports an unusual case of laceration of the trachea in an 8-week-old infant with a history of prolonged neonatal intubation needed to treat hyaline membrane disease. After diagnosis the tracheal injury was managed conservatively. Factors involved in the occurrence of the injury and its management are discussed.


Refractory duodenal ulcer healing and relapse: comparison of omeprazole with Helicobacter pylori eradication.
To investigate differences between omeprazole and Helicobacter pylori eradication in patients with duodenal ulcers refractory to H2-receptor antagonists and to compare the recurrence rates after the two treatments. Forty-five patients with endoscopically proven duodenal ulcers refractory to H2-receptor antagonists and H. pylori infection were randomly assigned to 8 weeks of treatment with omeprazole 40 mg/day or 4 weeks of treatment with colloidal bismuth subcitrate 480 mg/day plus metronidazole 750 mg/day and tetracycline 1000 mg/day from day 1 to day 14. Patients were evaluated endoscopically and clinically at the end of treatment. Patients with healed ulcers were followed up for 1 year after cessation of the treatment. Endoscopy was performed at 3 and 12 months. Ulcer healing occurred in 100% (21/21) of patients on triple therapy and 70.5% (12/17) of those treated with omeprazole alone (P = 0.0123). The relapse rate at the 3rd month was 11.7% (2/17) in the triple therapy group and 60% (6/10) in the omeprazole group (P = 0.0248). Of the patients followed to study endpoint (relapse or endoscopy at 12 months) three of 12 (25%) receiving triple therapy, compared to six of eight (75%) receiving omeprazole, relapsed (P = 0.0648). These results show that triple therapy is more effective than omeprazole in the treatment of refractory duodenal ulcers and reduces the rate of ulcer relapse.


A spatial equilibrium model for region size, urbanization ratio, and rural structure.
"Earlier economic models of city size have either focused on urban agglomeration effects while ignoring the spatial structure of the rural hinterland, or made unrealistic assumptions (for example, uniform rural population distribution) so as to simplify the problem. Following the classic von Thunen framework, we present a two-sector spatial equilibrium model of a city located at the center of an agricultural hinterland. The city produces industrial goods, and the rural area produces agricultural goods. Both goods are consumed both by urban and by rural residents. Market equilibrium for these goods determines: (1) the spatial size of the region, (2) the urbanization ratio (urban to total population) and the population size of the city, and (3) the rural spatial structure (wage, population distribution, land rent, and agricultural yield). Given various sets of exogenous parameters pertaining to the industrial, agricultural, and transportation production functions and to population preferences, the model is solved numerically, and response functions are estimated and analyzed."


Viruses, cytokines, antigens, and autoimmunity.
To explain the pathogenesis of autoimmunity, we hypothesize that following an infection the immune response spreads to tissue-specific autoantigens in genetically predisposed individuals eventually determining progression to disease. Molecular mimicry between viral and self antigens could, in some instances, initiate autoimmunity. Local elicitation of inflammatory cytokines following infection probably plays a pivotal role in determining loss of functional tolerance to self autoantigens and the destructive activation of autoreactive cells. We also describe the potential role of interleukin 10, a powerful B-cell activator, in increasing the efficiency of epitope recognition, that could well be crucial to the progression toward disease.


Psychiatric DRGs: more risk for hospitals?
The diagnosis related group (DRG) system, which replaced the cost-plus system of reimbursement, was implemented in 1983 by Medicare to cover medical expenses on a prospective basis. To date, the DRG system has not been applied to psychiatric illness. The authors compare the likelihood of cost overruns in psychiatric illness with that of cost overruns in medical illness. The data analysis demonstrates that a prospective payment system would have a high likelihood of failure in psychiatric illness. Possible reasons for failure include wide variations in treatments, diagnostics, and other related costs. Also, the number of DRG classifications for psychiatric illness is inadequate.


Interaction of cyclin-dependent kinase 2 and the Lyn tyrosine kinase in cells treated with 1-beta-D-arabinofuranosylcytosine.
The cyclin dependent kinase 2 (Cdk2) is required for initiation and progression of DNA replication. Activation of Cdk2 involves binding to cyclin E or cyclin A and dephosphorylation of Tyr15. The present studies demonstrate that treatment of U-937 cells with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with tyrosine phosphorylation of Cdk2 and inhibition of Cdk2 activity. The results also demonstrate that Cdk2 directly associates with the Src-like tyrosine kinase Lyn as a consequence of ara-C-treatment. Confocal microscopy studies show that Lyn is detectable in the nucleus and that it colocalises with Cdk2. Subcellular fractionation and coimmunoprecipitation studies further demonstrate nuclear binding of Lyn and Cdk2. We also show that Lyn phosphorylates Tyr15 of Cdk2 and that incubation of Lyn with Cdk2 results in inhibition of Cdk2 activity. These findings suggest that the association of Lyn and Cdk2 in ara-C-treated cells may contribute to regulation of Cdk2-dependent cell cycle checkpoints.


Functional characterization of human IgG, IgM, and IgA antibody directed to the capsule of Haemophilus influenzae type b.
Antibody to the capsular polysaccharide (CP) of Haemophilus influenzae b (Hib) is bactericidal, opsonic, and protective. Minimum protective levels of primarily IgG antibody to Hib CP, calculated from passive immunization studies, have been found to be approximately .06-.15 microgram/ml of serum. The human response to antigenic challenge with the Hib capsule, however, includes production of antibody to Hib CP of different isotypes whose function against Hib is unclear. In order to characterize the function of antibody to Hib CP of different isotypes, we purified human IgG, IgM, and IgA from the serum of an adult donor who had been previously immunized with purified Hib CP vaccine. The globulin preparations were greater than 99% isotypically pure, contained large quantities of anticapsular antibody, and differed in function against Hib. IgG antibody to Hib CP was bactericidal and opsonic for human polymorphonuclear leukocytes (PMNLs) in the presence of complement and protective in infant rats. IgM, although more bactericidal than IgG (P less than .01) and equally protective in rats, opsonized Hib poorly for PMNLs. IgA was not bactericidal or opsonic and did not prevent bacteremia and meningitis in rats challenged with Hib. We conclude that antibody directed against the capsule of Hib differs in antibacterial function depending on class. These data may be important to acurately estimate minimum protective levels of anticapsular antibody after vaccination or natural infection and may have implications for the manner in which the host clears Hib from the circulation.


The complete chloroplast genome of Caroxylon passerinum (Chenopodiaceae), an annual desert plant.
Caroxylon passerinum is an important constructive species, which is widely distributed in both desert and desert steppe in north-western China. C. passerinum is one of hosts of holoparasitic Cistanche species. In this study, we report the complete chloroplast genome sequence of C. passerinum, which is 150,925 bp in length and comprises a large single-copy region (83,057 bp), a small single-copy region (18,180 bp), and a pair of inverted repeats (24,844 bp). It encodes 132 unique genes, including 89 protein-coding genes (PCGs), 35 tRNAs, and eight rRNAs. The overall GC content of this chloroplast genome is 36.8%. Maximum likelihood (ML) phylogenetic tree strongly supports that C. passerinum is closely related to the hosts of Cistanche deserticola, Haloxylon persicum and Haloxylon ammodendron.


Developmental plasticity of physiology and morphology in diet-restricted European shag nestlings (Phalacrocorax aristotelis).
Growing animals may exhibit developmental plasticity as an adaptation to variability in the environmental conditions during development. We examined physiological and morphological responses to short-term food shortage of 12-16-day-old European shag nestlings kept under laboratory conditions. After 4 days on a weight maintenance diet, the resting metabolic rate (RMR) of diet-restricted nestlings was 36.5% lower compared with control fed nestlings, after controlling for body mass. This response was accompanied by a reduction in body temperature (T(b)) and by reductions in the size of several visceral organs, muscles and lipid stores, while the overall structural growth was maintained almost in line with the age-specific growth rate of controls. Hence, the pattern of energy allocation reflected a very high priority to structural growth at the expense of visceral organs, lipid deposits and muscles. The reduced T(b) and size of the liver served as important physiological processes behind the observed reductions in RMR. We discuss the possible adaptive significance of this differential developmental plasticity during temporal food shortage. This is the first study of avian developmental plasticity to report substantial energy saving in combination with a high structural growth rate.


L-29, a soluble lactose-binding lectin, is phosphorylated on serine 6 and serine 12 in vivo and by casein kinase I.
L-29, a mammalian soluble lactose-binding lectin, was previously shown to be phosphorylated in confluent 3T3 fibroblasts (Cowles, E. A., Agrwal, N., Anderson, R. L., and Wang, J. L. (1990) J. Biol. Chem. 265, 17706-17712), which contain a small amount of this protein. We have determined the site of phosphorylation on L-29, taking advantage of the abundance of L-29 (about 1% of total soluble cell protein) in confluent polarized Madin-Darby canine kidney (MDCK) cells. Approximately 15-20% of the L-29 is phosphorylated in these cells. Phosphoamino acid analysis showed phosphate incorporation only at serine. Analysis of chymotryptic and endoproteinase Asp-N-generated NH2-terminal fragments by Edman degradation showed that 90% of the phosphate was at Ser6 and 10% at Ser12. The sequence surrounding Ser6, which is conserved in all known L-29 sequences, indicated that this serine might be phosphorylated by casein kinase I or casein kinase II. Reaction of human recombinant L-29 with [gamma-32P]ATP and each of these casein kinases showed that only casein kinase I catalyzed significant incorporation of 32P into L-29; and, as with the L-29 from the MDCK cell extracts, most of the phosphate was incorporated at Ser6 and a small amount was incorporated at Ser12.


Peripheral-type benzodiazepine receptor antagonist is effective in relieving neuropathic pain in mice.
cDNA microarray analysis showed the expression of peripheral-type benzodiazepine receptor (PBR) mRNA is slightly enhanced in the spinal cord of mice with spinal nerve injury (SNL) as compared with sham-operated mice. PBR transports cholesterol to the mitochondria, where cholesterol is converted to pregnenolone. Pregnenolone is then metabolized to progesterone, an activator of progesterone receptor, and further metabolized to produce allopregnanolone and 3alpha,21-dihydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THDOC), positive allosteric modulators and activators of the GABA(A) receptor. In the present study, we first tested whether the enhanced PBR expression is causally related to neuropathic pain, and we found that the PBR antagonist PK11195 is effective in reducing SNL-induced mechanical allodynia and thermal hyperalgesia. Next we tested whether the PK11195-induced antinociception is attributable to reduced neurosteroid synthesis, which may possibly lead to reduced activation of the progesterone receptor and/or GABA(A) receptor. We found that allopregnanolone and 3alpha,5alpha-THDOC are effective in reducing the anti-hyperalgesic effect of PK11195, suggesting a partial contribution of reduced GABA(A)-receptor activation to PK11195-induced antinociception.


Potential bone fragility of mid-shaft atypical femoral fracture: Biomechanical analysis by a CT-based nonlinear finite element method.
The authors previously reported a CT-based nonlinear finite element analysis (nonlinear CT/FEA) model to investigate loading stress distribution in the femoral shaft of patients with atypical femoral fractures (AFFs). This showed that stress distribution, influenced primarily by femoral bowing, may determine the location of AFF. Here, we demonstrate the locational characteristics associated with AFFs in an Asian, specifically Japanese, population regarding bone strength. This is the second report from our multicentre research project suggesting a possible new concept of diagnostic criteria or treatment according to AFF subtype. A multicentre prospective study was conducted at 12 hospitals in Japan from August 2015 through June 2018. We recruited three study groups composed of elderly females over the age of 60 years-the mid-shaft AFF group (n = 14; 80.0 ± 6.5 years), the subtrochanteric AFF group (n = 15; 73.9 ± 6.8 years), and the control group who had sustained unilateral hip fracture (n = 21; 82.1 ± 7.1 years)-and analysed femoral neck bone density and strength. Bone strength of the femoral neck was predicted with an evaluation method using nonlinear CT/FEA in both standing and falling configuration. Femoral neck bone density and strength were significantly higher in the subtrochanteric AFF group compared with the mid-shaft AFF and control groups (p < 0.0001). No significant difference was seen in bone strength between the mid-shaft AFF and control groups (standing, p = 0.7616; falling, p = 0.3803). AFF has different features, in terms of bone strength, depending on fracture location. At the very least, Japanese patients with mid-shaft AFF could be at high risk of hip fracture because of bone fragility, in contrast to the firm bone of subtrochanteric AFF. For internal fixation of mid-shaft AFF using an IM nail, cervical screw insertion toward the femoral head might be recommended to prevent possible hip fracture.


Nonrandom dimerization of murine leukemia virus genomic RNAs.
Retroviral genomes consist of two unspliced RNAs linked noncovalently in a dimer. Although these two RNAs are generally identical, two different RNAs can be copackaged when virions are produced by coinfected cells. It has been assumed, but not tested, that copackaging results from random RNA associations in the cytoplasm to yield encapsidated RNA homodimers and heterodimers in Hardy-Weinberg proportions. Here, virion RNA homo- and heterodimerization were examined for Moloney murine leukemia virus (MLV) using nondenaturing Northern blotting and a novel RNA dimer capture assay. The results demonstrated that coexpressed MLV RNAs preferentially self-associated, even when RNAs were identical in known packaging and dimerization sequences or when they differed overall by less than 0.1%. In contrast, HIV-1 RNAs formed homo- and heterodimers in random proportions. We speculate that these species-specific differences in RNA dimer partner selection may at least partially explain the higher frequency of genetic recombination observed for human immunodeficiency virus type 1 than for MLV.


Promiscuous archaeal ATP synthase concurrently coupled to Na+ and H+ translocation.
ATP synthases are the primary source of ATP in all living cells. To catalyze ATP synthesis, these membrane-associated complexes use a rotary mechanism powered by the transmembrane diffusion of ions down a concentration gradient. ATP synthases are assumed to be driven either by H(+) or Na(+), reflecting distinct structural motifs in their membrane domains, and distinct metabolisms of the host organisms. Here, we study the methanogenic archaeon Methanosarcina acetivorans using assays of ATP hydrolysis and ion transport in inverted membrane vesicles, and experimentally demonstrate that the rotary mechanism of its ATP synthase is coupled to the concurrent translocation of both H(+) and Na(+) across the membrane under physiological conditions. Using free-energy molecular simulations, we explain this unprecedented observation in terms of the ion selectivity of the binding sites in the membrane rotor, which appears to have been tuned via amino acid substitutions so that ATP synthesis in M. acetivorans can be driven by the H(+) and Na(+) gradients resulting from methanogenesis. We propose that this promiscuity is a molecular mechanism of adaptation to life at the thermodynamic limit.


High-Capacitance Pseudocapacitors from Li+ Ion Intercalation in Nonporous, Electrically Conductive 2D Coordination Polymers.
Electrochemical capacitors (ECs) have emerged as reliable and fast-charging electrochemical energy storage devices that offer high power densities. Their use is still limited, nevertheless, by their relatively low energy density. Because high specific surface area and electrical conductivity are widely seen as key metrics for improving the energy density and overall performance of ECs, materials that have excellent electrical conductivities but are otherwise nonporous, such as coordination polymers (CPs), are often overlooked. Here, we report a new nonporous CP, Ni3(benzenehexathiolate) (Ni3BHT), which exhibits high electrical conductivity of over 500 S/m. When used as an electrode, Ni3BHT delivers excellent specific capacitances of 245 F/g and 426 F/cm3 in nonaqueous electrolytes. Structural and electrochemical studies relate the favorable performance to pseudocapacitive intercalation of Li+ ions between the 2D layers of Ni3BHT, a charge-storage mechanism that has thus far been documented only in inorganic materials such as TiO2, Nb2O5, and MXenes. This first demonstration of pseudocapacitive ion intercalation in nonporous CPs, a class of materials comprising thousands of members with distinct structures and compositions, provides important motivation for exploring this vast family of materials for nontraditional, high-energy pseudocapacitors.


Pituitary dysfunction, morbidity and mortality with congenital midline malformation of the cerebrum.
The purpose of this study was to review systematically a series of patients with congenital midline brain defects and pituitary dysfunction in early childhood and to quantitate the degree of dysfunction and clinical outcome. This study was a retrospective analysis of case notes of patients with pituitary dysfunction associated with either a midline cerebral anomaly and/or optic nerve hypoplasia. Forty patients were studied: 2 with semilobar holoprosencephaly, 2 with lobar holoprosencephaly, 18 with septo-optic dysplasia with an intact septum pellucidum, 7 with septo-optic dysplasia with an absent septum pellucidum, 7 with agenesis of the corpus callosum and 4 patients with isolated pituitary hypoplasia. An early age of diagnosis, feeding difficulties, neurodevelopmental disability, visual impairment and seizures were common occurrences. Despite disordered neuro-anatomy, most seizure disorders were caused by hypoglycaemia or hypernatraemia. Hypotensive/hypoglycaemic crises accounted for two out of three deaths within the study population. Most of patients had multiple pituitary hormone deficiency with growth hormone and adrenocorticotrophic hormone deficiency occurring most commonly. Unequivocal isolated hypothalamic dysfunction was an uncommon finding. In congenital midline brain malformation there is a spectrum of disordered neuro-anatomy associated with variable pituitary dysfunction. Clinical manifestations such as convulsions and developmental delay may be due to disordered metabolism and/or neuro-anatomy. Children with congenital midline brain defects frequently manifest convulsions, neurodevelopmental disability and poor growth due to disordered metabolism and/or neuro-anatomy. Treating clinicians must be aware of the complex, dynamic neurological and metabolic nature of these patients and their potential for early demise.


Benchmarking: a data-oriented look at improving health care performance.
Benchmarking uses measures of comparative performance to develop an understanding of what is possible and how others have achieved higher levels of performance. Companies measure each other's performance, identify the best performer out of a group, and then seek to identify and understand the practices that can improve both clinical and administrative operations. When a powerful consortium of Cincinnati businesses began addressing ways to lower the cost of employee care in a project known as the Iameter study, the University of Cincinnati Hospital joined the effort to identify and improve major cost factors. One aspect highlighted by this review is the length of stay in the neonatal intensive care unit (NICU). The results of the study were incorporated into an NICU early discharge program, which has had a number of positive effects in both patient care quality and cost containment.


MCF-7 cells as a three-dimensional model for the study of human breast cancer.
The increasing use of three-dimensional (3D) cell culture is because it reproduces in vitro results similar to in vivo results. Multicellular tumor spheroids generated in vitro exhibit important characteristics of avascular tumors, mainly with respect to tumor physiology and microenvironment. The interaction among cells in a tridimensional culture environment enhances cell differentiation and leads to luminal formation in some breast-derived cell cultures. The present work describes a method that permits luminal formation in breast adenocarcinoma cell (MCF-7)-derived spheroids in a 3D environment. In the proposed model, several relevant parameters, such as cell survival, apoptosis, autophagy, and E-cadherin expression, were analyzed to understand the organization of MCF-7 cells during different culture phases, including luminal and bud formation.


Absence of a diastolic velocity notch does not indicate hyperemia in traumatic brain injured patients without elevated cerebral blood flow velocity.
Elevated blood flow velocity (BFV), measured by transcranial Doppler (TCD), has been associated with hyperemia and cerebral vasospasm. This study examined whether the lack of a diastolic notch within the TCD waveform was associated with relative hyperemia within 5 days after injury in 35 traumatic brain injured (TBI) patients. Hyperemia (avD(O2) of < 4 ml/dL) was present in 16 patients and absent in 19 patients. Two clinicians independently coded TCD waveforms based on the presence of a diastolic notch (88% agreement). There was no significant difference in the presence of a diastolic notch by group; a diastolic notch was present in 57% (11/19) of patients without hyperemia and 81% (13/16) of patients with hyperemia. Sensitivity and specificity of detecting hyperemia using the diastolic notch was 18.7% and 57.9% respectively. The results showed that relative hyperemia was present without an elevation in blood flow velocities, and that the lack of a diastolic notch did not detect the presence of hyperemia in the TBI patient.


Structure-Guided Immobilization of an Evolved Unspecific Peroxygenase.
Unspecific peroxygenases (UPOs) are highly promiscuous biocatalyst with self-sufficient mono(per)oxygenase activity. A laboratory-evolved UPO secreted by yeast was covalently immobilized in activated carriers through one-point attachment. In order to maintain the desired orientation without compromising the enzyme's activity, the S221C mutation was introduced at the surface of the enzyme, enabling a single disulfide bridge to be established between the support and the protein. Fluorescence confocal microscopy demonstrated the homogeneous distribution of the enzyme, regardless of the chemical nature of the carrier. This immobilized biocatalyst was characterized biochemically opening an exciting avenue for research into applied synthetic chemistry.


Light activation of ribulose bisphosphate carboxylase: purification and properties of the enzyme in tobacco.
The development of methods of preparation of long wavelength ultraviolet light capable of activating ribulose bisphosphate carboxylase is reported. This preparation was obtained from tobacco (Nicotiana tabacum) leaves which had reached about one-half maximum leaf weight. It was prepared at low ionic strength by use of mixed anion and cation exchange resins and buffers containing dimethylsulfoxide. The preparation is greatly enriched in fraction I protein to the point of apparent homogeneity. When assayed in the presence of saturating ribulose bisphosphate and sodium bicarbonate, the rate of carbon fixation is a linear function of long wavelength ultraviolet irradiation in the range of 20,000 to 30,000 ergs per square centimeter per second. Glutathione (5 mm) inhibits light activation without affecting activity in the dark. Copper sulfate inhibits both light and dark activity, but is slightly less effective in the presence of ultraviolet light. Sucrose inhibition of carboxylation is only readily apparent in the absence of ultraviolet light. Ammonium sulfate precipitation followed by solubilization in buffers containing dimethylsulfoxide plus heat treatment promotes ultraviolet light activation.


Specific interaction in vitro and in vivo of glyceraldehyde-3-phosphate dehydrogenase and LA protein with cis-acting RNAs of human parainfluenza virus type 3.
Human parainfluenza virus type 3 (HPIV3) genome RNA is transcribed and replicated by the virus-encoded RNA-dependent RNA polymerase, and specific cellular proteins play a regulatory role in these processes. To search for cellular proteins potentially interacting with HPIV3 cis-acting regulatory RNAs, a gel mobility shift assay was used. Two cellular proteins specifically interacted with the viral cis-acting RNAs containing the genomic 3'-noncoding region and the plus-sense leader sequence region. Surprisingly, by biochemical and immunological analyses, one of the cellular proteins was identified as the key glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The other protein was characterized as the autoantigen, LA protein. Both GAPDH and LA protein also interacted with the same cis-acting RNA sequences in vivo and were found to be associated with the HPIV3 ribonucleoprotein complex in the infected cells. By double immunofluorescent labeling, GAPDH was found to be co-localized with viral ribonucleoprotein in the perinuclear region. These observations strongly suggest that cellular GAPDH and LA Protein participate in the regulation of HPIV3 gene expression.


The effect of the menstrual cycle on anterior cruciate ligament injuries in women as determined by hormone levels.
Anterior cruciate ligament injury rates are reported to be two to eight times higher in women than in men within the same sport. Because the menstrual cycle with its monthly hormonal fluctuations is one of the most basic differences between men and women, we investigated the association between the distribution of confirmed anterior cruciate ligament tears and menstrual cycle phase. Sixty-nine female athletes who sustained an acute anterior cruciate ligament injury were studied within 24 hours of injury at four centers. The mechanism of injury, menstrual cycle details, use of oral contraceptives, and history of previous injury were recorded. Urine samples were collected to validate menstrual cycle phase by measurement of estrogen, progesterone, and luteinizing hormone metabolites and creatinine levels at the time of the anterior cruciate ligament tear. Results from the hormone assays indicate that the women had a significantly greater than expected percentage of anterior cruciate ligament injuries during midcycle (ovulatory phase) and a less than expected percentage of those injuries during the luteal phase of the menstrual cycle. Oral contraceptive use diminished the significant association between anterior cruciate ligament tear distribution and the ovulatory phase.


Influence of ethanol on the rennet-induced coagulation of milk.
The influence of ethanol on the rennet-induced coagulation of milk was studied to investigate potential synergistic effects of these two mechanisms of destabilisation on the casein micelles. Addition of 5% (v/v) ethanol reduced the rennet coagulation time (RCT) of milk, whereas higher levels of ethanol (10-20%, v/v) progressively increased RCT. The temperature at which milk was coagulable by rennet decreased with increasing ethanol content of the milk. The primary stage of rennet coagulation, i.e., the enzymatic hydrolysis of kappa-casein, was progressively slowed with increasing ethanol content (5-20%, v/v), possibly due to ethanol-induced conformational changes in the enzyme molecule. The secondary stage of rennet coagulation, i.e., the aggregation of kappa-casein-depleted micelles, was enhanced in the presence of 5-15% ethanol, the effect being largest at 5% ethanol. Enhanced aggregation of micelles is probably due to an ethanol-induced decrease in inter-micellar steric repulsion. These results indicate an interrelationship between the effects of ethanol and chymosin on the casein micelles in milk, which may have interesting implications for properties of dairy products.


Effect of monovalent anions on the mechanism of phenol hydroxylase.
The mechanism of phenol hydroxylase (EC 126.96.36.199) has been studied by steady state and rapid reaction kinetic techniques. Both techniques give results consistent with the Bi Uni Uni Bi ping-pong mechanism proposed for other flavin-containing aromatic hydroxylases. The enzyme binds phenolic substrate and NADPH in that order, followed by reduction of the flavin and release of NADP+. A transient charge transfer complex between reduced enzyme and NADP+ can be detected. Molecular oxygen then reacts with the reduced enzyme-substrate complex. Two to three flavin-oxygen intermediates can be detected in the oxidative half-reaction depending on the substrate, provided monovalent anions are present. Oxygen transfer is complete with the formation of the second intermediate. Based on its UV absorption spectrum and on the fact that oxygen transfer has taken place, the last of these intermediates is presumably the flavin C(4a)-hydroxide. Monovalent anions are uncompetitive inhibitors of phenol hydroxylase. The mechanistic step most affected is the dehydration of the flavin C(4a)-hydroxide to give oxidized enzyme. Chloride also kinetically stabilizes the blue flavin semiquinone of phenol hydroxylase during photoreduction. These data suggest binding of monovalent anions results in stabilization of a proton on the N(5) position of the flavin.


CpG DNA analysis of bacterial STDs.
Bacterial infections in the genital tract frequently result in morbidity through a variety of inflammation based symptoms. One component of the bacteria that may trigger host inflammatory response is their DNA. CpG motifs in this DNA are known targets for Toll-like receptor 9 (TLR9), which is a pathogen-recognition receptors focusing on CpG DNA. The activation of TLR9 induces the NF-κB inflammatory pathway. This study aims to provide a broad view of the inflammatory potential of CpG DNA motifs in bacteria related to genital diseases: C. trachomatis, E. coli, N. gonorrhoeae, G. vaginalis, H. ducreyi, L. crispatus, L. gasseri, M. hominis, M. genitalium, T. pallidum, and U. urealyticum. Publicly available genomic sequences of the bacterial species and strains have been analyzed in silico to produce a CpG index number. This CpG index number shows the relative inflammatory potential of the genome and has previously been used in a study by Lundberg et al. (2003). Higher CpG index values suggest a strong CpG induced inflammation potential during infection and vice versa. The highest observed CpG index belongs to G. vaginalis with a value of 26,2, suggesting a strong pro-inflammatory potential when in contact with TLR9. The lowest index belongs to N. gonorrhoeae with a value of -79,5, suggesting a strong immunoinhibitory effect on TLR9 contact. Interestingly, Lactobacilli showed a mean CpG index value of 4,2, suggesting a weak inflammatory potential. Our results show varying CpG index values between bacterial species. Comparison of CpG indices with the clinical course of several pathogens shows the CpG index helps clarify the clinical course of infection. However, we found no links between CpG index values and either obligate pathogenicity or facultative pathogenicity through bacterial vaginosis. Lactobacilli showed relatively low CpG indices which do suggest a lower inflammatory potential from these bacteria. Our results show varying CpG index values between bacterial species, which may help clarify the clinical course of infection, and may help diagnosis.


Simulation for supporting scale-up of a fluidized bed reactor for advanced water oxidation.
Simulation of fluidized bed reactor (FBR) was accomplished for treating wastewater using Fenton reaction, which is an advanced oxidation process (AOP). The simulation was performed to determine characteristics of FBR performance, concentration profile of the contaminants, and various prominent hydrodynamic properties (e.g., Reynolds number, velocity, and pressure) in the reactor. Simulation was implemented for 2.8 L working volume using hydrodynamic correlations, continuous equation, and simplified kinetic information for phenols degradation as a model. The simulation shows that, by using Fe(3+) and Fe(2+) mixtures as catalyst, TOC degradation up to 45% was achieved for contaminant range of 40-90 mg/L within 60 min. The concentration profiles and hydrodynamic characteristics were also generated. A subsequent scale-up study was also conducted using similitude method. The analysis shows that up to 10 L working volume, the models developed are applicable. The study proves that, using appropriate modeling and simulation, data can be predicted for designing and operating FBR for wastewater treatment.


[A cross-sectional study on liver diseases in the rural residents in southern Guangxi, China].
To study the epidemiological characteristics of liver diseases in a rural population in Southern Guangxi, China. The enzyme immunoassays was used to detect of HBsAg and AFP. AFP positive serum samples were further examined for concentration of AFP by using a radio immunoassays. Liver morphological changes were measured with ultrasonography of type B. The positive rates of HBsAg in the studied population was 17.8% (2800/15,701). The prevalence rates of viral hepatitis B, cirrhosis, primary liver cancer, clonorchiasis, fatty liver disease, alcoholic liver disease were 1.1% (173/15,701), 0.4% (63/15,701), 299.3 per 100,000 (47/15,701), 6.6% (1036/15,701), 4.8% (754/15,701) and 0.3% (47/15,701), respectively. The positive rates of HBsAg and the prevalence rates of viral hepatitis B, cirrhosis, primary liver cancer, clonorchiasis, fatty liver disease in male were significantly higher as compared with those in female (5.98 < or = chi(2) < or = 394.78, P < 0.01). No difference was observed in the prevalence rates of liver cavernous hemangioma and hepatic cysts between male and female. The prevalence rates of intrahepatic bile duct stones was significantly higher in female than in male (chi(2) = 30.80, P < 0.01). The positive rates of HBsAg and the prevalence rates of viral hepatitis B and clonorchiasis were decreased with age. But the prevalence rates of cirrhosis, primary liver cancer, fatty liver disease, alcoholic liver disease, liver cavernous hemangioma, hepatic cysts and intrahepatic bile duct stones were increased with age. The rural areas in the southern Guangxi are high prevalence regions of liver illness, and the male resident are even at high risk.


Anti-inflammatory and antioxidant effect of ginger in tuberculosis.
Tuberculosis (TB) has reemerged to become the world's leading cause of death from a single infectious agent. Inflammatory cytokines play an important role during the course of the disease and may be responsible for tissue damage by lipid peroxidation. The study was aimed to explore the anti-inflammatory and antioxidant effect of ginger in pulmonary TB patients. A total of 69 pulmonary TB patients participated in a randomized and placebo-controlled study. The intervention group received 3 g of ginger extract daily for 1 month and placebo group was supplemented with starch capsule. Participants of both groups were taking standard antitubercular treatment during the study. The concentrations of tumor necrosis factor (TNF) alpha, ferritin and malondialdehyde (MDA) in blood samples were analyzed before and after the intervention by using enzyme-linked immunosorbent assay for TNF alpha and ferritin and spectrophotometry for MDA. Ginger supplementation significantly reduced the levels of TNF alpha, ferritin and MDA in ginger supplemented group in comparison to baseline. Ginger supplementation with antitubercular treatment significantly lowered TNF alpha, ferritin and MDA concentrations in comparison to control group. Ginger was found to be effective as an anti-inflammatory and antioxidant supplement along with anti-TB therapy as it possesses strong free radical scavenging property.


Monitoring lung compliance and end-tidal oxygen content for the detection of venous air embolism.
Venous air embolism (VAE) is a recognized complication of surgery performed with the patient in the sitting position, but it occurs also during other operations. We report two cases of VAE, associated with a notable decrease in dynamic lung compliance, detected by side-stream spirometry. Based on these cases, an experiment with 10 pigs was designed to evaluate the usefulness of side-stream spirometry in the diagnosis of VAE. Three doses of air (0.5, 1.0 and 2.0 ml kg-1) were injected via the proximal part of a 5- French gauge pulmonary artery catheter. Only the largest dose was followed by haemodynamic deterioration. Significant increases in end-tidal oxygen content and decreases in dynamic lung compliance were detected with all doses of air together with conventional signs of VAE, that is increases in pulmonary artery pressures and arterial carbon dioxide tensions, and decreases in end-tidal concentration of carbon dioxide. We conclude that continuous monitoring of end-tidal oxygen concentration and side-stream spirometry offers valuable supplements to other monitoring techniques in the detection of VAE.


A new device for intraoperative renal blood flow measurement during open-heart surgery: an experimental study and the clinical pilot study.
Renal blood flow (RBF) may vary during cardiopulmonary bypass and low flow may cause insufficient blood supply of the kidney triggering renal failure postoperatively. Still, a valid intraoperative method of continuous RBF measurement is not available. A new catheter combining thermodilution and intravascular Doppler was developed, first calibrated in an in vitro model, and the catheter specific constant was determined. Then, application of the device was evaluated in a pilot study in an adult cardiovascular population. The data of the clinical pilot study revealed high correlation between the flow velocities detected by intravascular Doppler and the RBF measured by thermodilution (Pearson's correlation range: 0.78 to 0.97). In conclusion, the RBF can be measured excellently in real time using the new catheter, even under cardiopulmonary bypass.


Subjective visual horizontal and stabilometer findings in patients with unilateral severe vestibular dysfunction.
The records of both stabilometer and subjective visual horizontal (SVH) testing can be used to evaluate vestibular compensation. When results of SVH testing have a strong significant correlation to those of stabilometer testing, clinicians can omit one of two tests from the test battery. To investigate the correlation, results of these two tests of patients with unilateral severe vestibular dysfunction were studied. Twenty-eight patients, 20 men and 8 women, with unilateral severe vestibular dysfunction were enrolled in this study. The correlation between these two tests was considered not significant according to the results. In conclusion, we cannot omit either stabilometer testing or SVH testing for the evaluation of patients with vestibular dysfunction.


[Significance of senescence study on tree roots and its advances].
Root system is one of the important components of trees, and has some important physiological functions such as nutrient and water absorption, transport and storage, anchoring, and supporting. After tree root systems formed, roots often suffer from nutrient- and water-deficient stress, and thus, their absorption of nutrients and water appears more important. Soil nutrient and water have a great spatiotemporal heterogeneity. As the heterogeneity occurs, trees regulate carbon partitioning to roots, resulting in the senescence or death of some roots of the whole root system. In forestry, the senescence of tree roots is closely related to tree productivity, because there is a close relationship between the senescence of tree roots and the absorption of soil nutrient and water. At ecosystem and global scale, the senescence of tree roots influences the cycling of carbon and nutrients, because roots exhaust a great deal of carbon fixed by source leaves through photosynthesis, and there are great amounts of nutrients in tree roots. The senescence of tree roots is influenced by many environmental factors, biotic (e.g., fungi, bacteria, viruses, small edaphic animals) and abiotic (e.g., water, temperature, soil nutrients, heavy metals). These factors affect the senescence of tree roots by different mechanisms. Although we have much knowledge on the senescence of tree roots and some hypotheses have been proposed, some problems still remain to be resolved, and further experiments are needed to test these hypotheses. Interdisciplinary studies integrating cytology, biochemistry, soil science, and genetics are the prerequisite for rapid advances in understanding the essence of tree root senescence.


Draft Genome Sequence of the Polyextremophilic Exiguobacterium sp. Strain S17, Isolated from Hyperarsenic Lakes in the Argentinian Puna.
Exiguobacterium sp. strain S17 is a moderately halotolerant, arsenic-resistant bacterium that was isolated from Laguna Socompa stromatolites in the Argentinian Puna. The draft genome sequence suggests potent enzyme candidates that are essential for survival under multiple environmental extreme conditions, such as high levels of UV radiation, elevated salinity, and the presence of critical arsenic concentrations.


Panic disorder subtypes: differential responses to CO2 challenge.
The purpose of this study was to investigate the possibility of a differential sensitivity to CO2 in patients diagnosed with panic disorder subtypes that were defined by the presence of prominent respiratory symptoms. The authors used a 35% CO2 and 65% O2 mixture as a challenge agent. Fifty-one unmedicated subjects with DSM-III-R panic disorder, who were divided into respiratory (N = 28) and nonrespiratory (N = 23) subtypes by their symptom profiles, underwent a CO2 challenge procedure. Patients in the two groups were compared with regard to physiological and psychological measures, pulmonary function tests, panic rates, and smoking habits. The patients in the respiratory group were significantly more sensitive to CO2 than were the patients in the nonrespiratory group. The respiratory group also had higher scores on the Panic and Agoraphobia Scale and had a longer duration of illness; both of these factors can be indicators of illness severity. In addition, the respiratory group's higher cigarette consumption (mean = 12.46 package-years, SD = 2.49) may have been a contributory factor not only for illness severity but also for the pathogenesis of panic disorder. The CO2 challenge procedure appears to be a good dissection tool in the understanding of different subtypes of panic disorder. Moreover, there may be a more specific association with prominent respiratory symptom subtype and CO2 hypersensitivity.


[Analysis of ARSA mutations in a Chinese family with metachromatic leukodystrophy].
To identify arylsulftase A gene (ARSA) mutations in a Chinese family with MLD. There were two MLD patients in the investigated family. The proband, an 11-year-old girl, was well until the age of 5 years, when she began to experience difficult walking and mental regression. Magnetic resonance imaging (MRI) of her brain showed widespread demyelination, nerve conduction velocity reduced, and ASA activity measured in white blood cells was zero. So, the child was diagnosed having MLD. The proband's young brother also got the same phenotype except clinical symptom being milder than hers. Their parents and elder sister all had normal phenotypes. Genomic DNA samples were extracted from peripheral bloods of the proband and all her family members. All 8 exons and exon-intron boundaries of ARSA gene were amplified by polymerase chain reaction (PCR) and followed by direct DNA sequencing. Two heterozygous mutations of ARSA, which were named as, G251A (R84Q) and G296T (G99V) were identified in the proband. The two mutations were located in exon 2. The same genotype was found in the proband's young brother, but these mutations were not detected in proband's elder sister. The proband's mother had the heterozygous mutations G296T (G99V), and her father had the heterozygous mutation G251A (R84Q). These two MLD patients are with both compound heterozygous mutations, which mean one allele with the G296T (G99V) mutation was from their mother, and the other allele with the G251A (R84Q) mutation got from their father. The parents are both carrier with normal phenotype.


Fibrolamellar hepatocellular carcinoma with skeletal metastases.
Skeletal metastases is relatively rare in hepatocellular carcinoma and accounts for 4-16% of extrahepatic metastases. The authors report a 13-year-old girl with fibrolamellar hepatocellular carcinoma, who rejected further systemic chemotherapy following hepatic lobectomy and experienced sternal and vertebral painful metastases nearly 5 years after the operation. The sternal metastatic lesion was removed surgically, whereas external irradiation was delivered to the lumbar vertebral lesion. The patient received no systemic treatment following metastases and died with widespread disease. Despite metastatic disease, the patient survived 6.5 years following the initial diagnosis.


Recurrent smoke-induced respiratory infections in a ruby blue-headed pionus parrot (Pionus menstruus rubrigularis).
A 4-year-old female blue-headed pionus parrot (Pionus menstruus rubrigularis) presented repeatedly for acute smoke inhalation. The protracted clinical course and secondary respiratory infections with multiple pathogens represented characteristic sequelae to smoke inhalation and toxicosis seen in other species, but these have not been previously reported in birds.


Uncertainties in internal doses calculated for Mayak workers--a study of 63 cases.
This study makes use of 63 cases of Mayak workers exposed to Pu-239 with autopsy data and some late-time urine bioassay data. In addition, air-concentration data--used to construct monthly average values--are available for each case, which provide the time dependence and potential magnitudes of normal inhalation intakes for each case. The purpose of the study is to develop and test Bayesian methods of dose calculation for the Mayak workers. The first part of the study was to quantitatively characterise the uncertainties of the bioassay data. Then, starting with three different published biokinetic models, the data are fit by varying intake and model perturbation parameters, e.g., parameters influencing the lung, thoracic lymph nodes, liver and bone retention. Statistical self-consistency arguments are used to check the measurement uncertainty parameters within the Poisson-lognormal model. The second part of the study is to set up and test Bayesian dose calculations, which use the point determinations of biokinetic parameters from the study cases within a discrete, empirical Bayes approximation. The main conclusion of the study is that these methods are now ready to be applied to the entire Mayak worker population.


Drinking sucrose or saccharin enhances sensitivity of rats to quinpirole-induced yawning.
Diet can impact sensitivity of rats to some of the behavioral effects of drugs acting on dopamine systems. The current study tested whether continuous access to sucrose is necessary to increase yawning induced by the dopamine receptor agonist quinpirole, or if intermittent access is sufficient. These studies also tested whether sensitivity to quinpirole-induced yawning increases in rats drinking the non-caloric sweetener saccharin. Dose-response curves (0.0032-0.32 mg/kg) for quinpirole-induced yawning were determined once weekly in rats with free access to standard chow and either continuous access to water, 10% sucrose solution, or 0.1% saccharin solution, or intermittent access to sucrose or saccharin (i.e., 2 days per week with access to water on other days). Cumulative doses of quinpirole increased then decreased yawning, resulting in an inverted U-shaped dose-response curve. Continuous or intermittent access to sucrose enhanced sensitivity to quinpirole-induced yawning. Continuous, but not intermittent, access to saccharin also enhanced sensitivity to quinpirole-induced yawning. In all groups, pretreatment with the selective D3 receptor antagonist PG01037 shifted the ascending limb of the quinpirole dose-response curve to the right, while pretreatment with the selective D2 receptor antagonist L-741,626 shifted the descending limb to the right. These results suggest that even intermittent consumption of diets containing highly palatable substances (e.g. sucrose) alters sensitivity to drugs acting on dopamine systems in a manner that could be important in vulnerability to abuse drugs.


Efficacy of olmesartan therapy on fibrinolytic capacity in patients with hypertension.
The efficacy of olmesartan on fibrinolytic capacity has not been studied yet. Therefore, the aim of the present study was to investigate the efficacy of olmesartan on hemostatic/fibrinolytic status by measuring plasma level of plasminogen activator inhibitor-1 (PAI-1) and soluble thrombomodulin levels in patients with hypertension. Forty-two consecutive, newly diagnosed (25 women and 17 men with a mean age of 48 ± 8 years) patients with untreated essential hypertension were included in the study. Olmesartan medoxomil (20 mg/day) was started and the patients were followed up for 6 months. Baseline biochemical variables, thrombomodulin, and PAI-1 levels were compared with the levels of these variables measured at the end of the 6-month follow-up period. After 6 months of treatment with olmesartan medoxomil, there was a significant reduction in systolic and diastolic blood pressure (from 159.5 ± 10.9 to 134.6 ± 12.7 mmHg and from 98.0 ± 6.3 to 83.9 ± 7.0 mmHg, respectively). Mean plasma PAI-1 and thrombomodulin levels were also significantly decreased (59.73 ± 41.91 vs. 48.60 ± 33.65 ng/ml, P = 0.001 and 8.09 ± 2.29 vs. 6.92 ± 1.42 μg/l, P < 0.001, respectively). Olmesartan medoxomil decreased plasma PAI-1 and thrombomodulin levels after 6 months of therapy, indicating a favorable effect on fibrinolytic capacity in patients with essential hypertension.


Adipose Stem Cell-Based Treatments for Wound Healing.
Wound healing is one of the most complex physiological regulation mechanisms of the human body. Stem cell technology has had a significant impact on regenerative medicine. Adipose stem cells (ASCs) have many advantages, including their ease of harvesting and high yield, rich content of cell components and cytokines, and strong practicability. They have rapidly become a favored tool in regenerative medicine. Here, we summarize the mechanism and clinical therapeutic potential of ASCs in wound repair.


'A pretty piece of treachery': the strange case of Dr Stekel and Sigmund Freud.
Freud claimed he broke with Stekel not because of 'scientific differences' but because of 'exclusively ... personal qualities'. The author offers an alternative version of this significant fragment of psychoanalytic history by suggesting that Freud acted out of revenge for the humiliation that he believed Stekel and Adler inflicted upon him at the 1910 Nuremberg Congress. He suggests that casting the story of the break between Stekel and Freud in the narrative shadow of Robert Louis Stevenson's novella 'Jekyll and Hyde' highlights the extent to which Freud involved himself in the murkier aspects of the politics of the International Psychoanalytical Association and the Vienna Psychoanalytic Society. Ultimately, however, he argues, Freud was cynically prepared to use and then callously sacrifice Stekel, one of his oldest and most loyal followers, in his increasingly bitter struggles against Adler and Jung. He also touches upon the role of the 'Secret Committee' in the 'Stekel Affair' and the wider ramifications of Jung's unexpected return from America at the height of the 'Freud resignation crisis'. He further suggests that Jung's subsequent meeting with Bergmann may have been a significant factor in precipitating Jung's decision to break his personal relationship with Freud.


Reliability of behavioral tests in the middle cerebral artery occlusion model of rat.
Stroke is one of the leading causes of death and disability worldwide, and its incidence is increasing. To overcome impairment from stroke, translational research for developing new therapeutic technologies has been conducted and middle cerebral artery occlusion (MCAo) in rat is the representative model. Since recovery from neurological impairment in contralateral limbs caused by brain damage is the major goal of treatment, behavioral tests that assess the relevant function are used. To determine therapeutic effect, obtaining reliable results of behavioral assessment is a prerequisite. However, studies on the reliability of behavioral tests in the MCAo rat model and necessity of prior training have not yet been reported. In this study, the authors investigate relative and absolute inter-rater reliabilities of modified neurological severity score (mNSS), cylinder test, and grid-walking test before training and repeated training every week until the reliability of results reached a satisfactory level. The training included repeated learning of the scoring system and decreasing disagreements among the raters. For MCAo modeling, adult male Sprague-Dawley rats were subjected to 90 min of transient MCAo. Six raters conducted behavioral tests via observation of video-recording on sham-operated and MCAo model rats at 3 or 7 days after the intervention. An independent experimenter randomly numbered each video clip to blind the experiment. The results of reliabilities were unacceptable before training and improved to a satisfactory level after 6 weeks of training in all of the tests. In conclusion, mNSS, cylinder test, and grid-walking test on the MCAo rat model are reliable evaluation methods after conducting appropriate training.


Enhancement of ethylene formation by selenoamino acids.
Selenomethionine and selenoethionine enhanced ethylene production in senescing flower tissue of Ipomoea tricolor Cav. and in auxin-treated pea (Pisum sativum L.) stem sections. This enhancement was fully inhibited by the aminoethoxy analog of rhizobitoxine. Methionine did not have a comparable promotive effect, and ethionine partly inhibited ethylene production. When [(14)C]methionine was applied to flower or pea stem tissue followed by treatment with unlabeled selenomethionine or selenoethionine, the specific radioactivity of the ethylene evolved was considerably reduced. The dilution of the specific radioactivity of ethylene by selenomethionine, and in pea stem sections also by selenoethionine, was greater than the dilution by nonradioactive methionine at the same concentration. These results indicate that both selenoamino acids serve as precursors of ethylene and that they are converted to ethylene more efficiently than is methionine.


A Unique Nanoflake-Shape Bimetallic Ti-Nb Oxide of Superior Catalytic Effect for Hydrogen Storage of MgH2.
MgH2 is one of the most promising solid hydrogen storage materials due to its high capacity, excellent reversibility, and low cost. However, its operation temperature needs to be greatly reduced to realize its practical applications, especially in the highly desired fuel cell fields. This work synthesizes a 2D nanoflake-shape bimetallic Ti-Nb oxide of TiNb2 O7 , which has high surface area and shows superior catalytic effect for the hydrogen storage of MgH2 . Incorporated with the TiNb2 O7 nanoflakes as low as 3 wt%, MgH2 shows a low onset dehydrogenation temperature of 178 °C, which is lowered by 100 °C compared with the pristine one. A dehydrogenation capacity as high as 7.0 wt% H2 is achieved upon heating to 300 °C. The capacity retention is as high as 96% after 30 cycles. The mechanism of the improved hydrogen storage properties is analyzed by density functional theory (DFT) calculation and the microstructural evolution during dehydrogenation and hydrogenation. This work provides an MgH2 system with high available capacity and low operation temperature by a unique structural design of the catalyst. The high surface area feature of the TiNb2 O7 nanoflakes and the synthesis method hopefully can develop the application of TiNb2 O7 .


Zebrafish dystrophin and utrophin genes: dissecting transcriptional expression during embryonic development.
Some genes can encode multiple overlapping transcripts, and this can result in challenges in identifying transcript-specific developmental expression profiles where tools such as RNA in situ hybrisations are inapplicable. Given this difficulty, we have undertaken a preliminary analysis of the developmental expression profile of selected transcripts of the dystrophin and utrophin genes of the zebrafish (Danio rerio) by targeting unique and common regions of each of these transcripts. The dystrophin and utrophin genes of zebrafish were identified by bioinformatic analysis and the dystrophin gene predictions were confirmed by transcript sequencing. These data enabled primer pairs to be designed in order to determine the expression profiles of unique, but overlapping transcripts, throughout embryonic development using quantitative real time reverse transcription PCR (qRT-PCR). The data indicated the early expression of the short carboxyl-terminal dystrophin transcript, with expression of the full length muscle transcript occurring during myogenesis. Importantly, a composite of these two profiles appeared to comprise the major transcriptional load of the zebrafish dystrophin gene. In contrast, utrophin gene expression was dominated by the full length transcript throughout embryogenesis. The approach described here provided a means by which a gene's transcriptional complexity can be deconvoluted to reveal transcriptional diversity during embryogenesis. This approach, however, required the identification of unique regions for transcript-specific targeting, and an appreciation of alternative splicing events that may compromise the design of primers for qRT-PCR.


Dedifferentiated Low-Grade Central Osteosarcoma of the Mandible.
We present the first, to our knowledge, case of a dedifferentiated low-grade central osteosarcoma (LCOS) of the mandible. A 48-year-old Japanese woman underwent enucleation under general anesthesia after a diagnosis of ossifying fibroma. At the second recurrence, the pathological diagnosis after biopsy was of sarcoma with MDM2(+) and CDK4(+) immunohistochemical staining results. Hemimandibulotomy, supraomohyoid neck dissection, and free-flap reconstruction with a rectus abdominal flap were performed. A retrospective reevaluation of the first specimen with additional immunohistochemical staining for MDM2 and CDK4 yielded a final diagnosis of dedifferentiated LCOS. The patient showed no recurrence or lung metastasis 3 years after the final surgery.


Job Exposure Matrix for Chrysotile Asbestos Fibre in the Asbestos Cement Manufacturing (ACM) Industry in Zimbabwe.
Occupational chrysotile asbestos exposure data in Zimbabwe is limited. The aim of this study was therefore to develop a job exposure matrix (JEM) specific to the chrysotile asbestos cement manufacturing industry using the available personal exposure concentration data. Quantitative personal exposure chrysotile fibre concentration data collected by the two factories from 1996 to 2020 were used to construct the JEM. Exposure groups from which data was extracted were classified based on the Zimbabwe Standard Classification of Occupations (ZSCO), 2009-2019. Analysis of amphiboles in raw chrysotile was done by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). Descriptive statistics, namely mean, standard deviation and range were computed for the main variable, job/occupation. All jobs/occupations in both factories had annual mean personal exposure concentrations exceeding the OEL of 0.1 f/mL, except for the period from 2009 to 2016 in the Harare factory and the period from 2009 to 2020 in the Bulawayo factory. Despite the Harare factory having no AC manufacturing activity since 2017, personal exposure concentrations showed elevated levels for the period 2018-2020. Amphiboles were detected in almost all bulk samples of chrysotile asbestos analysed. The established JEM, which has been generated from actual local quantitative exposure measurements, can be used in evaluating historical exposure to chrysotile asbestos fibre, to better understand and predict occurrence of ARDs in future.


[FTIR assessment of the secondary structure of proteins in royal jelly under different storage conditions].
The quality of royal jelly has a high positive correlation with its storage periods and temperature. In the present paper, Fourier transform infrared spectra (FTIR) of royal jelly was measured with different temperatures and storage periods, and the compositions of the secondary structure of protein were determined by curve-fitting analysis of the amide I bands in the FTIR spectra. The results showed that the spectral differences were observed among these types of samples, the composition of the secondary structures of protein exhibited extreme difference, and the rate of alpha-helix decreased and beta-sheet increased dramatically with the increase in storage temperature and periods. The content of beta-turn also tended to increase, and the order of their change extent was 28 degrees C > 16 degrees C > 4 degrees C > -18 degrees C. These results met the theory that royal jelly should be kept under lower temperature. So, FTIR spectroscopy combined with several data-processing methods, such as secondary derivative, deconvolution, and curve fitting would be an effective method for assessing the quality and freshness of royal jelly.


[Prediction of remission in Graves' disease after thionamide therapy by technetium-99m early uptake].
In the clinical management of Graves' thyrotoxicosis, one of the most important subject is when to stop antithyroid drugs after achieving an euthyroid state. T3 suppression test and other methods have been used to forecast the outcome after drug cessation, but the results were not always satisfactory. We have attempted to predict remission of Graves' disease by single measurement of early technetium uptake without administration of triiodothyronine. Drugs were discontinued in the seventy-five patients with Graves' disease on maintenance doses of either methimazole or propylthiouracil who showed normalized uptake (4.0% or less). Of 64 patients evaluable after twelve months, 55 (86%) remained euthyroid, 8 relapsed, and 1 became hypothyroid. With its accuracy in prediction of short-term remission comparable or superior to T3 suppression test, this rapid and simple method seemed suitable for routine use in clinical practice.


Cardiotoxin II segregates phosphatidylglycerol from mixtures with phosphatidylcholine: (31)P and (2)H NMR spectroscopic evidence.
The interaction of the cationic protein cardiotoxin II (CTX II) with mixtures of zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and anionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) was investigated using phosphorus ((31)P) and deuterium ((2)H) nuclear magnetic resonance (NMR) spectroscopy. Adding CTX II to 1:1 POPC/POPG mixtures produced a two-component (31)P NMR spectrum, in which the second component had a decreased chemical shift anisotropy. Simultaneously, the (2)H NMR quadrupolar splitting measured from both POPC-alpha-d(2) and POPC-beta-d(2) decreased. Thus, CTX II produces an altered macroscopic phase state of the lipid bilayers, and this obscures any effects on bilayer surface electrostatics observed by (2)H NMR. Using magic angle spinning (MAS) (31)P NMR spectroscopy, two isotropic resonances were resolved in the absence of CTX II and were assigned to POPG (0.47 ppm) and POPC (-.58 ppm). Adding CTX II produced two new isotropic resonances shifted approximately 0.5 ppm downfield. Quantifying the intensities of the various resonance lines revealed that the binding isotherms for different POPC/POPG mixtures shifted onto a universal curve when expressed as a function of the CTX II/POPG ratio. The results indicate that CTX II binds preferentially to POPG and is able to laterally segregate POPG from POPC. Fitting of the binding isotherms was achieved using a two-site model derived from statistical-thermodynamic considerations. One class of binding site is specific for POPG and the other is nonspecific, capable of binding both POPC and POPG.


Yolk Sac Tumor in an Infant with Androgen Insensitivity Syndrome: A Case Report and Review of the Literature.
Background: Androgen insensitivity syndrome (AIS) is a disorder of sexual differentiation caused by complete or partial resistance to the biological action of androgens. The common malignant tumors associated with this syndrome are seminomas. However, the risk of malignancy in childhood remains low. Case Report: A 8-month-old child with a female phenotype and a 46, XY karyotype, presented with bilateral inguinal hernia. The patient underwent right radical inguinal orchiectomy with high ligation of the spermatic cord and laparoscopic percutaneous extra-peritoneal herniorrhaphy. Final pathology confirmed a pure yolk sac tumor (YST) from the right testis. Androgen receptor (AR) gene mutation was found in the children. The follow-up ultrasonography shown no recurrence, with serum AFP returned to normal within 3 months. Conclusion: The case we presented is relatively infrequent in the literature with yolk sac tumor in a AIS children presented with a palpable lump inguinal region.


[A case of sphenoid sinus mucocele].
Infection of the sphenoid sinus is an uncommon clinical entity frequently misdiagnosed because of its vague symptoms and paucity of clinical findings. We report a case of sphenoid sinus mucocele complicated by retro-orbital pain and ipsilateral optic atrophy. CT scan and MR image revealed a cystic mass lesion of the sphenoid sinus. Bone around the lesion was eroded. The patient underwent transnasal drainage of the cystic mass. We conclude that transnasal drainage is the safest method of treatment of an infectious lesion in and around the sphenoid sinus.


Simian virus 40 and human tumors: It is time to study mechanisms.
Several studies found simian virus 40 (SV40) in 47% to 83% of human mesotheliomas. Mesotheliomas are malignant tumors of the pleura and peritoneum, firmly associated with asbestos exposure. In this issue, Gazdar and colleagues ¿Shivapurkar et al., 1999 found that SV40 is present only in the malignant cells and not in the surrounding stromal cells. Using the microdissection technique, they found SV40 in 54% of 93 mesotheliomas of the epithelial type. The surrounding reactive stromal cells, (20 lung cancers and 14 mesotheliomas of the sarcomatoid/fibrous type) did not contain SV40, confirming the specificity of their positive findings. Furthermore, SV40 was found in 14% of 14 non-malignant reactive mesothelial cell proliferations. In 12 cases of mesothelioma a noninvasive (or in situ) component was also identified. In all four cases in which SV40 sequences were present in the invasive component, sequences were also present in the accompanying noninvasive component. These data suggest that the virus resides in the mesothelial cells prior to tumor development. The data address the remaining concerns raised at an International Meeting organized by the NIH, FDA, and CDC in 1997 to definitively associate SV40 with human mesothelioma. It is time now to investigate the pathogenic mechanisms of this association, and if SV40-infected mesothelial cells are more susceptible to other carcinogens, such as asbestos. Furthermore, we must investigate the interaction between the host immune system and SV40-infected mesothelial cells, and study if the immunosuppressive activity of asbestos interferes with tumor rejection. These studies should lead to a better understanding of mesothelioma pathogenesis, and possibly to new therapeutic approaches aimed at interfering with the expression of the SV40 genome and/or at eliciting a strong immune response against SV40 infected mesothelial cells.


Technology-driven triage of abdominal trauma: the emerging era of nonoperative management.
Selective nonoperative management of blunt or penetrating abdominal trauma is safe, has eliminated the complications associated with nontherapeutic laparotomies, and is cost-effective. Appropriately selected investigations, such as focused abdominal sonography for trauma, diagnostic peritoneal lavage, spiral computed tomography (CT) scan, diagnostic laparoscopy, or thoracoscopy and angiography, play a critical role in the triage of patients. Future technological advances, such as improvement of the ultrasonic hardware and software that provide automated interpretation and the availability of portable CT scan machines in the emergency room, may improve the speed and accuracy of the initial evaluation. Improvement of the optical system of minilaparoscopes may allow reliable bedside laparoscopy for suspected diaphragmatic injuries.


Distinct physiological roles of the Gq-coupled metabotropic glutamate receptors Co-expressed in the same neuronal populations.
The group I metabotropic glutamate receptors, mGluR1 and mGluR5, exhibit a high degree of sequence homology, and are often found co-expressed in the same neuronal populations. These receptors couple to a broad array of effector systems, and are implicated in diverse physiological and pathophysiological functions. Due to the high degree of sequence homology, and the findings that these receptors couple identically in recombinant systems, it has been generally assumed that these two group I mGluR subtypes would exhibit redundant function when coexpressed in the same neurons. With the advent of subtype-selective pharmacological tools, it has become possible to tease apart the functions of mGluR1 and mGluR5 in the same neuron. The emerging picture is one of diverse function, which implies differential regulation. Interestingly, the group I mGluRs are modulated by a rich variety of regulatory systems, which may explain how these receptors can mediate divergent actions when present in the same cell.


A novel application of microwave-assisted extraction of polyphenols from brewer's spent grain with HPLC-DAD-MS analysis.
This paper reports a novel application of microwave-assisted extraction (MAE) of polyphenols from brewer's spent grains (BSG). A 2(4) orthogonal composite design was used to obtain the optimal conditions of MAE. The influence of the MAE operational parameters (extraction time, temperature, solvent volume and stirring speed) on the extraction yield of ferulic acid was investigated through response surface methodology. The results showed that the optimal conditions were 15 min extraction time, 100 °C extraction temperature, 20 mL of solvent, and maximum stirring speed. Under these conditions, the yield of ferulic acid was 1.31 ± 0.04% (w/w), which was fivefold higher than that obtained with conventional solid-liquid extraction techniques. The developed new extraction method considerably reduces extraction time, energy and solvent consumption, while generating fewer wastes. HPLC-DAD-MS analysis indicated that other hydroxycinnamic acids and several ferulic acid dehydrodimers, as well as one dehydrotrimer were also present, confirming that BSG is a valuable source of antioxidant compounds.