Clustering and percolation in lithium borate glasses.
Molecular dynamics simulations are carried out in xLi2O-(1-x)B2O3 glasses (x=0.2-0.6) at T=1250 K, where cluster size distributions for Li cations and nonbridging oxygen (NBO) atoms are calculated. The existence of percolating clusters above x=0.3 places the percolation threshold between x=0.3 and 0.4 for the system under investigation, which is consistent with the abrupt increase of the diffusion coefficient of Li cations observed at x=0.4. It is also shown that the clusters of Li cations consist mainly of Li atoms found in the vicinity of NBO atoms. This result explains the higher mobility exhibited by this type of cations compared to the mobility of Li cations in the vicinity of bridging oxygen atoms.


Pacing Strategy in Men's 400 m Hurdles Accounting for Temporal and Spatial Characteristics of Elite Athletes.
The final result in a 400 m hurdles race (400mH) is relative to the motor preparation, technique of clearing hurdles as well as the adopted strategy of the race, including temporal aspects (split times in particular parts of the race) and spatial elements (the number of strides taken between subsequent hurdles). The objective of the study was to identify an optimal strategy for the 400mH race, including the stride pattern and split times. Data employed for this study were derived from results of 273 races held during the men's finals of international events (Olympic Games, World and European Championships) held from 1968 to 2015. To determine the strategies in the race, three main hurdle sections were identified - 1-4H, 4-7H and 7-10H. In each part, the fast (best results), average and slow (worst results) performing groups of hurdlers were distinguished. The analysis of adopted strategies was carried out taking into account 26 variables (main, basic, temporal and spatial). Basic statistical data, correlations and analysis of variance (ANOVA) were used. Results highlight the use of a variety of strategies, of which selection depends, among others, on body composition and the level of motor abilities (speed, speed endurance and explosive strength), as well as hurdling technique. Especially, the endurance strategy appears to be the most effective one, as it is a characteristic of best performances of many hurdlers. The analysis demonstrates that at the highest sports level the strategy of 400 m hurdles should be analyzed individually.


Behavioral effects of phenoxybenzamine administered intraventricularly in rats.
Phenoxybenzamine (PNB) injected into the lateral ventricle of the brain weakens spontaneous motility of rats and antagonizes hyperactivity induced with noradrenaline, amphetamine and caffeine. Body temperature rises briefly, sleep induced with chloral hydrate is shortened, and high doses enhance amphetamine-induced stereotypy. PNB injected intraventricularly intensifies turnover of noradrenaline but it has no effect on turnover of dopamine in rat brains. The results confirm a blocking influence of PNB on the cerebral noradrenaline receptors.


Anterior cruciate ligament injuries in the National Football League: epidemiology and current treatment trends among team physicians.
To review the epidemiology of anterior cruciate ligament (ACL) injuries in the National Football League (NFL) and current treatment trends within this population. Descriptive. Part 1 of this study reviews the data collected in the NFL Injury Surveillance System from 1986 to 1995 with respect to these injuries. Included in this review are the specifics surrounding these injuries such as exposure type (game versus practice), position, mechanism, and playing surface on which the injury occurred. Part 2 of this analysis focuses on present treatment performed on these high-level athletes through a survey that was sent to and completed by all 31 NFL team orthopaedic surgeons. The total number of ACL injuries in this select population has remained constant over the period analyzed. Current preferred treatment technique favors endoscopic patellar tendon autograft reconstruction.


Determination of tissue plasminogen activator and its "fast" inhibitor in plasma.
We describe efficient, accurate methods for specific determination of tissue plasminogen activator (t-PA, EC 188.8.131.52) and its "fast" inhibitor in plasma. In this coupled assay, a sample containing t-PA is incubated with plasminogen, a plasmin (EC 18.104.22.168) substrate of low Km and high Kcat, and fibrin as a stimulator. The inhibitor of t-PA is determined by incubating the sample with a known amount of t-PA in excess, then determining the residual t-PA. Both t-PA and t-PA inhibitor can be determined in many samples simultaneously within a few hours. These assays are modifications of procedures described by us (Clin Chim Acta 1983;127:279-88 and Thromb Res 1983;31:427-36). Their accuracy as assessed by analytical recovery of pure t-PA added to blood samples (91 +/- 4%) or of partly purified inhibitor added to plasma samples (102 +/- 10%) is satisfactory, as is their precision. For the t-PA assay the CV was 1.6% (within run) or 4.1% (between run). The corresponding values for the inhibitor assay were 4.5% (within run) or 8.4% (between run) if the inhibitor concentration exceeded 3 arb. units/mL.


[STUDY OF DIRECT TB-LAMP USING NON-CENTRIFUGAL SPUTUMS ABOUT EFFICIENCY FOR RAPID DIAGNOSIS OF TUBERCULOSIS].
To evaluate the efficiency of the direct tuberculosis-loop-mediated isothermal amplification (TB-LAMP) assay by using non-centrifuged sputum samples. STUDY PERIOD AND METHODS: The study was conducted between June 2013 and February 2014. We collected 111 sputum samples from patients who had been radiographically diagnosed with tuberculosis and had not received any treatments for longer than 5 days. In the direct TB-LAMP assay, a loop-mediated isothermal amplification kit and 60-μL sputum samples were used. A direct smear microscopy test was used as the smear test. Then, the same sputum samples were processed with a CCE pretreatment reagent, and 100 μL of the solution samples were cultured by using the mycobacterial growth indicator tube (MGIT) culture method. Forty-six of the 111 samples were positive in the smear microscopy tests. All the smear-positive samples were positive in both the MGIT and direct TB-LAMP assay (100%). The mean positive detection time with the direct TB-LAMP assay was 13 minutes 55 seconds. Of 56 smear-negative and MGIT positive samples, 44 (78.6%) were judged to be positive using the direct TB-LAMP assay, with a mean positive detection time of 15 minutes 59 seconds. The direct TB-LAMP assay using non-centrifuged sputum samples was demonstrated to have a high detection rate and thus may be considered useful for rapid and effective tuberculosis diagnosis.


Activation of a covalent outer membrane phospholipase A dimer.
The activity of outer membrane phospholipase A (OMPLA) is regulated by reversible dimerization. However, native OMPLA reconstituted in phospholipid vesicles was found to be present as a dimer but nevertheless inactive. To investigate the importance of dimerization for control of OMPLA activity, a covalent OMPLA dimer was constructed and its properties were compared to native OMPLA both in a micellar detergent and after reconstitution in a phospholipid bilayer. Unlike native OMPLA, activity of the covalent OMPLA dimer was independent of type and concentration of detergent in micellar systems. In such systems, the covalent OMPLA dimer invariantly displayed high calcium affinity. In contrast, high calcium concentrations were required to activate a covalent OMPLA dimer when present in intact vesicles. Solubilization of the vesicles increased the affinity for calcium, suggesting that in an intact bilayer the dimer interface is not properly formed. This was supported by the observation that OMPLA variants having an impaired dimeric interface also lacked high affinity calcium binding. A covalent linkage was not able to restore high affinity calcium binding in these variants, demonstrating that a proper dimer interface is essential for optimal catalysis.


Activin receptor signaling.
Activin is a member of the TGF-beta superfamily and has various effects on diverse biological systems. Activins initiate their cellular responses by binding to their receptors with intrinsic serine/threonine kinase activity and activation of specific downstream intracellular effectors termed Smad proteins. Smads relay the signal from the cell membrane to the nucleus, where they affect the transcription of target genes. Negative regulation of activin signal occurs at the extracellular, membrane, cytoplasmic and nuclear levels. The presence of many mechanisms for regulation shows its importance to normal physiology. Here, we review the latest advances in activin signal transduction.


How stress alters immune responses during respiratory infection.
Fall-weaned calves entering the feedlot experience a variety of psychological and physical stressors, including maternal separation, transportation, social mixing, restraint, and dietary changes. Mixing calves from multiple sources also exposes them to respiratory pathogens at a time when maternal immunity has waned. Using an experimental bovine respiratory disease (BRD) challenge, we analyzed the effects of specific stressors on clinical disease and immune responses following bovine herpes virus (BHV-1/IBR) infection of naïve calves. Transportation stress was compared to either abrupt weaning plus transportation or transportation following a two-step weaning process. Transportation alone significantly (P < 0.05) increased BHV-1 shedding in nasal secretions despite elevated interferon-gamma production in the upper respiratory tract. In contrast, abrupt weaning and transportation, significantly (P < 0.05) increased serum haptoglobin on day 3 post-infection (PI) and blood leukocyte tumor necrosis factor α secretion on day 5 PI. These systemic responses were reduced by instituting a two-step weaning process 4 days prior to transportation and BHV-1 infection. In conclusion, these observations are consistent with earlier studies implicating weaning and transportation as stressors contributing to BRD severity and mortality. Current studies also revealed that different stressors or combination of stressors have distinct effects on host responses to viral infection in naïve calves.


[The possibilities of improving the treatment of chronic heart failure according to the results of a multicenter observational study BYHEART].
To study the efficacy and safety of exogenous phosphocreatine (EF) in patients with chronic heart failure (CHF). The all-Russian prospective observational study BYHEART included 842 patients who were treated with EF. Before and after the course of EF therapy, the following studies were conducted: a questionnaire on the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and a clinical condition assessment scale (SHOCK), transthoracic echocardiography with an assessment of the left ventricular ejection fraction, a 6-minute walk test, determination of the level of pro-natriuretic N-terminal peptide (NT-proBNP), glomerular filtration rate. All patients before the course of EF received long-term optimal drug therapy of CHF. Statistical analysis was carried out in the general group of patients (n=842), as well as in groups of patients A (n=418, the course of treatment of EF is less than 20 g /course) and group B (n=424, the course of treatment of EF is greater than or equal to 20 g/course). The results obtained demonstrate a positive effect of the use of the course of therapy of EF in patients with CHF on the quality of life (QOL), reverse left ventricular remodeling, functional class of CHF, as well as the concentration of NT-pro-BNP, especially in the group of patients who received more than 20 grams of the medication. The use of EF is a promising pharmacological method of treatment in addition to optimal drug therapy in patients with CHF.


PDCD5 promotes cisplatin-induced apoptosis of glioma cells via activating mitochondrial apoptotic pathway.
Glioma is one of the most common primary brain tumors. Despite surgical resection, radiotherapy, and chemotherapy, the prognosis of patients with malignant glioma remains poor. Programmed cell death 5 (PDCD5) is a newly described pro-apoptotic protein. Our previous study showed that PDCD5 downregulation in gliomas was associated with higher pathological grade. Here, we investigated the effect of PDCD5 on chemosensitivity of glioma cells and its mechanism. We demonstrated that overexpression or knockdown of PDCD5 had no significant effect on the proliferation of glioma cell lines (U87, U251, and T98G) in the absence of chemotherapeutic agents. However, PDCD5 overexpression effectively sensitized U87 cells to chemotherapeutic drugs (cisplatin, carboplatin, and vincristine) in a concentration-dependent manner, while its knockdown resulted in decreased chemosensitivity in U251, T98G, and U87 cells. Importantly, expression of PDCD5 also markedly inhibited tumor cell proliferation and colony formation in the presence of low doses of cisplatin. Furthermore, we found that PDCD5 expression promoted cisplatin-induced apoptosis, increased markedly the activation of caspase-3 and caspase-9, and decreased significantly the ratio of Bcl-2/Bax proteins, but had no effect on the activation of caspase-8. Taken together, our findings indicate that PDCD5 promotes chemosensitivity by activating mitochondria-related apoptotic pathway, and that the combination of PDCD5 and chemotherapeutic drugs such as cisplatin, is expected to be an effective therapeutic strategy for the malignant glioma.


Characterization of brain natriuretic peptide in long-term follow-up of pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) leads to substantial morbidity and mortality. Noninvasive parameters in the follow-up assessment of PAH could be helpful in clinical decision making. The brain natriuretic peptide (BNP) has been shown to correlate with the functional status and prognosis of these patients and could be a valuable parameter in this respect. The aim of our study was to investigate whether BNP levels could reflect clinical and hemodynamic changes, including the response to therapy during long-term follow-up in patients with PAH. We measured pulmonary hemodynamics, functional parameters including the 6-min walk distance (6MWD), and plasma BNP levels at baseline and after a mean (+/- SEM) follow-up period of 12.6 +/- 1.5 months in patients with PAH. In group A (n = 18), with decreasing BNP levels mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) decreased (PAP, 60.89 +/- 3.44 to 53.47 +/- 3.24 mm Hg; PVR, 1,207.47 +/- 111.75 to 942.35 +/- 103.15 dyne.s.cm(-5); p < 0.01) and 6MWD increased (408.24 +/- 29.57 to 470 +/- 25.54 m; p < 0.01). In group B (n = 12), with increasing BNP levels mean PAP and PVR increased (PAP, 52 +/- 3.31 to 60.17 +/- 5.03 mm Hg; PVR, 946.13 +/- 115.35 to 1,236.6 +/- 180.23 dyne . s . cm(-5); p < 0.01) and mean 6MWD decreased from 463.64 +/- 27.77 to 367.27 +/- 38.87 m (p < 0.05). Comparing groups revealed statistically significant differences regarding changes in PAP (group A, -11.58 +/- 3.57%; group B, +13.29 +/- 5.44%; p = 0.001) and PVR (group A, -19.21 +/- 5.87%, group B, +30.35 +/- 7.72%; p < 0.001). Correlations existed between the changes in BNP levels and pulmonary hemodynamics. We concluded that BNP levels parallel changes in pulmonary hemodynamics and functional parameters, including the 6MWD, in PAH patients. Consequently, we suggest BNP as a parameter for the follow-up assessment of PAH patients.


Strategies to limit CNS malpractice liability exposure.
The number of nurses named as defendants in medical malpractice cases is increasing. The CNS may be especially vulnerable in this legal climate. The complexity and diversity of the CNS role expose the CNS to an increased risk of malpractice liability in a variety of situations. Malpractice judgments and verdicts are used to describe the legal milieu that the CNS practicing in the various roles may encounter. The CNS roles examined are that of: clinician, educator, consultant, and researcher. The liabilities inherent in each of the CNS roles are defined, as well as strategies to limit malpractice liability exposure.


Inhibition of peptidoglycan, ribonucleic acid, and protein synthesis in tolerant strains of Streptococcus mutans.
Exposure of exponentially growing cultures of Streptococcus mutans strains FA-1 and GS-5 to various concentrations of benzylpenicillin (Pen G) resulted in inhibition of turbidity increases at low concentrations (0.02 to 0.04 mug/ml). However, in contrast to some other streptococcal species, growth inhibition was not accompanied by cellular lysis or by a rapid loss of viability. In both strains, synthesis of insoluble cell wall peptidoglycan was very sensitive to Pen G inhibition and responded in a dose-dependent manner to concentrations of about 0.2 and 0.5 mug/ml for strains GS-5 and FA-1, respectively. Higher Pen G concentrations failed to inhibit further either growth or insoluble peptidoglycan assembly. Somewhat surprisingly, Pen G also inhibited both ribonucleic acid (RNA) and protein syntheses, each in a dose-dependent manner. Compared with inhibition of peptidoglycan synthesis, inhibition of RNA and protein syntheses by Pen G was less rapid and less extensive. Maximum amounts of radiolabeled Pen G were specifically bound to intact cells upon exposure to about 0.2 and 0.5 mug/ml of Pen G for strains GS-5 and FA-1, respectively, concentrations consistent with those that resulted in maximum or near-maximum inhibitions of the synthesis of cellular peptidoglycan, RNA, and protein. Five polypeptide bands that had a very high affinity for [(14)C]Pen G were detected in a crude cell envelope preparation of strain FA-1. After exposure of cultures of strain FA-1 to the effects of saturating concentrations of the drug for up to 3 h, addition of penicillinase was followed by recovery of growth after a lag. The length of the lag before regrowth depended on both Pen G concentration and time of exposure. On the basis of these and other observations, it is proposed that the secondary inhibitions of cellular RNA or protein synthesis, or both, are involved in the tolerance of these organisms to lysis and killing by Pen G and other inhibitors of insoluble peptidoglycan assembly.


Facts and artifacts in the blinking statistics of semiconductor nanocrystals.
Since its initial discovery just over a decade ago, blinking of semiconductor nanocrystals has typically been described in terms of probability distributions for durations of bright, or "on," states and dark, or "off," states. These distributions are obtained by binning photon counts in order to construct a time series for emission intensity and then applying a threshold to distinguish on states from off states. By examining experimental data from CdSe/ZnS core/shell nanocrystals and by simulating this data according to a simple, two-state blinking model, we find that the apparent truncated power-law distributions of on times can depend significantly on the choices of binning time and threshold. For example, increasing the binning time by a factor of 10 can double the apparent truncation time and change the apparent power-law exponent by 30%, even though the binning time is only 3% of the truncation time. Our findings indicate that stringent experimental conditions are needed to accurately determine blinking-time probability distributions. Similar considerations should apply to any phenomenon characterized by time series data that displays telegraph noise.


Structure and Mechanism of the Divalent Anion/Na⁺ Symporter.
Integral membrane proteins of the divalent anion/Na⁺ symporter (DASS) family are conserved from bacteria to humans. DASS proteins typically mediate the coupled uptake of Na⁺ ions and dicarboxylate, tricarboxylate, or sulfate. Since the substrates for DASS include key intermediates and regulators of energy metabolism, alterations of DASS function profoundly affect fat storage, energy expenditure and life span. Furthermore, loss-of-function mutations in a human DASS have been associated with neonatal epileptic encephalopathy. More recently, human DASS has also been implicated in the development of liver cancers. Therefore, human DASS proteins are potentially promising pharmacological targets for battling obesity, diabetes, kidney stone, fatty liver, as well as other metabolic and neurological disorders. Despite its clinical relevance, the mechanism by which DASS proteins recognize and transport anionic substrates remains unclear. Recently, the crystal structures of a bacterial DASS and its humanized variant have been published. This article reviews the mechanistic implications of these structures and suggests future work to better understand how the function of DASS can be modulated for potential therapeutic benefit.


Serum Phospholipid Fatty Acid Composition in Cystic Fibrosis Patients with and without Liver Cirrhosis.
Cystic fibrosis (CF) liver disease is the third most frequent cause of death in CF patients. Although it alters fatty acid (FA) metabolism, data concerning the profile of FA in CF patients with liver cirrhosis is lacking. This study aimed to assess the FA composition of serum phospholipids in CF patients with and without liver cirrhosis. The study comprised 25 CF patients with liver cirrhosis and 25 without it. We assessed Z-scores for body height and weight, lung function, exocrine pancreatic sufficiency and colonization with Pseudomonas aeruginosa. FAs' profile of serum glycerophospholipids was quantified by gas chromatography mass spectrometry. In CF patients with liver cirrhosis, the levels of C16:0 were higher and the amounts of C20:2n-6, C20:3n-6, C20:4n-6, and all the n-3 polyunsaturated FAs (PUFAs) (C18:3n-3, C20:5n-3, C22:5n-3, C22:6n-3) were lower than those in CF subjects without liver cirrhosis. The n-6/n-3, C20:4n-6/C18:2n-6, total n-6/C18:2n-6, C20:5n-3/C18:3n-3 and total n-3/C18:3n-3 ratios did not differ between the 2 groups. Liver cirrhosis may associate with profound abnormalities in the composition of serum glycerophospholipids FAs in CF patients. None of the analyzed clinical factors could explain the greater prevalence of low levels of PUFAs in this CF subgroup.


Ghrelin plasma concentration does not covary with energy demand in adult laying hens.
The peptide hormone ghrelin is suggested to be involved in food intake regulation in young growing chicken. Whether ghrelin is involved in the regulation of energetic balance associated with laying performance in adult laying hens was studied by use of 4 chicken lines that differ in laying performance and phylogeny (4 lines; 16 hens per line). As housing conditions are also known to affect energy demand, half of the hens per line were housed in single cages and the other half of hens were maintained in a floor housing system. Plasma samples were collected at 17 to 19, 33 to 35, 49 to 51, and 72 wk of age and analyzed with a chicken ghrelin ELISA Kit. From caged hens, individual food consumption and laying performance additionally was recorded. Due to its function in growth and its relationship with ghrelin, also GH plasma concentrations were analyzed. Ghrelin concentrations did not differ between the 4 lines at any of the test periods (all P > 0.05). Ghrelin was negatively related to food consumption only in the growing period of the high-performing lines (both P < 0.0001). During this phase, floor-housed hens showed greater ghrelin concentrations compared with caged hens (P < 0.0001). Our results suggest that in adult layers ghrelin is not involved in regulating energy intake related to laying performance but rather seems to be related to body growth and housing condition before start of lay, the latter possibly due to differences in hens' behavioral activity.


Protozoal infections in the acquired immunodeficiency syndrome.
Several protozoa have emerged as the major opportunistic infections and cause of death in patients with acquired immunodeficiency syndrome (AIDS). Pneumocystis carinii pneumonia is the leading cause of death in AIDS patients. Electron microscopy (EM) usually shows numerous trophozoites and cysts of Pneumocystis filling up the entire alveolar space, while only cysts are seen under the light microscope. The focal thickening of cyst wall of Pneumocystis, as demonstrated by EM and manifested as a "parentheses" shaped structure with silver stain, serves as a diagnostic marker for Pneumocystis. Freeze-fracture EM has demonstrated the intimate contact between Pneumocystis trophozoites and the type I pneumocytes, which may contribute to the alveolar-capillary block, leading to severe respiratory distress. However, EM is seldom needed for the diagnosis of this infection. Toxoplasma encephalitis, which is an unusual clinical manifestation in cases of toxoplasmosis reported previously, has become a common complication and one of the major causes of death in patients with AIDS. Because subclinical infection by Toxoplasma is common, serologic tests usually offer no definite answers as to whether the infection is acute or chronic, active or past. The small size and its non-specificity in both morphology and tissue affinity make light microscopic diagnosis of toxoplasmosis difficult. Only immunologic staining, such as immunoperoxidase and immunofluorescence, can help to achieve a definite positive identification of the organism. When special antibodies or facility for such staining is not available, EM is the final resort for identifying Toxoplasma by showing the apical complex with the characteristic sausage-shaped rhoptries. Cryptosporidiosis, practically unknown before the AIDS outbreak, has become one of the most common intestinal protozoa in both immunocompromised and immunocompetent patients. The protracted and sometimes fatal course of cryptosporidiosis in immunocompromised patients can be explained by the presence of autoinfective oocysts (thin-walled oocysts), as detected by EM, and by recycling of first-generation schizonts observed experimentally. While diagnosis of cryptosporidiosis can be made by detection of oocysts in stools in most cases, EM is still the last resort for a definitive identification of Cryptosporidium species. While the incidence of isosporiasis is still low, it has been found more frequently in patients with AIDS than in the general population. The parasite, Isospora belli, being a coccidian as is the Cryptosporidium species, is similar to the latter in its life cycle and clinical manifestations.(ABSTRACT TRUNCATED AT 400 WORDS)


[Factor VII for a molecular marker in hypercoagulable state].
We measured factor VII activity and antigen levels in plasma of pregnant women and patients with elevated serum FDP including patients with DIC who were supposed to be in hypercoagulable state, and compared the values with normal subjects. Both FVII activities measured by human placenta thromboplastin (hTF/FVIIc) and bovine brain thromboplastin (bTF/FVIIc) in normal plasma were correlated well with the FVII antigen levels (FVIIag). Measured hTF/FVIIc, bTF/FVIIc and FVIIag in pregnant women were 163 +/- 44%, 205 +/- 49% and 175 +/- 44% respectively, and each value had correlation. Thrombin-antithrombin III complex in these subjects was increased (7.85 +/- 2.25 mg/ml). However, antithrombin III, plasmin-plasmin inhibitor complex and FDP D-dimer were within normal range. These observations indicated that pregnant women were in hypercoagulable state but not in hyperfibrinolytic state. hTF/FVIIc, bTF/FVIIc and FVIIag in plasma from patients with elevated serum FDP were 59.6 +/- 29%, 94 +/- 65% and 61.6 +/- 26% respectively. We divided these patients into 2 groups: Group A (both prolonged PT and APTT) and Group B (shortened APTT). hTF/FVIIc, bTF/FVIIc and FVIIag in plasma of Group A were 47 +/- 21%, 48 +/- 24% and 48 +/- 21% respectively. The corresponding values of Group B were 80 +/- 24%, 155 +/- 54% and 74 +/- 23% which were correlated each other. Low levels of FVII observed in Group A seemed to be due to increased consumption of coagulation factors. In Group B, the pattern of FVII activities and FVII antigen was similar to that of pregnant women, though FVII levels were lower.(ABSTRACT TRUNCATED AT 250 WORDS)


Knowledge of the health hazard of asbestos prior to the Merewether and Price report of 1930.
The first realization of the burden of ill health associated with occupational exposure to asbestos dust, and the need for environmental control, is generally dated from the publication of the results of the survey by Merewether and Price in 1930. A review of the literature and of associated archival material throws a different light on history. There was a wealth of evidence available prior to 1930 that should have led to earlier effective control. The responsibility for this delay must be shared between manufacturers, workers' representatives, the Factory Inspectorate and Scientists involved in the relevant research.


Human chromosome 8.
The role of human chromosome 8 in genetic disease together with the current status of the genetic linkage map for this chromosome is reviewed. Both hereditary genetic disease attributed to mutant alleles at gene loci on chromosome 8 and neoplastic disease owing to somatic mutation, particularly chromosomal translocations, are discussed.


Sphingosine-1-phosphate attenuates hypoxia/reoxygenation-induced cardiomyocyte injury via a mitochondrial pathway.
Our previous study showed that Sphingosine-1-phosphate (S1P) could protect cardiomyocytes against hypoxia/reoxygenation (H/R) injury via the JAK-STAT pathway and maintain normal myocardial mitochondria integrity in vivo. However, it is not known yet whether S1P can relieve mitochondrial dysfunction via the mitochondrial apoptotic pathway and its detailed mechanism remains to be investigated. The aim of this study was to demonstrate the mitochondrial protective effects of S1P in a cardiomyocyte H/R injury model. In the present study, we established a H/R model in H9c2 cells. Cell viability was determined by the MTT assay, and apoptosis was evaluated by annexin V-FITC/PI staining. Mitochondrial calcium ion concentration, mitochondrial membrane potential (ΔΨm), opening of the mitochondrial permeability transition pore (mPTP), and release of cytochrome C were detected by laser confocal microscopy. The results showed that S1P inhibited the decrease in cell viability induced by H/R injury and reduced apoptosis. Confocal microscopy showed that S1P prevented loss of ΔΨm, relieved mitochondrial calcium overload, and inhibited opening of the mPTP and release of cytochrome C. The STAT3 inhibitor STATTIC can reverse the antiapoptotic effects of S1P and block the effect of S1P on mitochondria. Taken together, our results indicate that S1P protects cardiomyocytes against H/R injury by relieving mitochondrial dysfunction via the STAT3 pathway.


Negative blood oxygen level dependent signals during speech comprehension.
Speech comprehension studies have generally focused on the isolation and function of regions with positive blood oxygen level dependent (BOLD) signals with respect to a resting baseline. Although regions with negative BOLD signals in comparison to a resting baseline have been reported in language-related tasks, their relationship to regions of positive signals is not fully appreciated. Based on the emerging notion that the negative signals may represent an active function in language tasks, the authors test the hypothesis that negative BOLD signals during receptive language are more associated with comprehension than content-free versions of the same stimuli. Regions associated with comprehension of speech were isolated by comparing responses to passive listening to natural speech to two incomprehensible versions of the same speech: one that was digitally time reversed and one that was muffled by removal of high frequencies. The signal polarity was determined by comparing the BOLD signal during each speech condition to the BOLD signal during a resting baseline. As expected, stimulation-induced positive signals relative to resting baseline were observed in the canonical language areas with varying signal amplitudes for each condition. Negative BOLD responses relative to resting baseline were observed primarily in frontoparietal regions and were specific to the natural speech condition. However, the BOLD signal remained indistinguishable from baseline for the unintelligible speech conditions. Variations in connectivity between brain regions with positive and negative signals were also specifically related to the comprehension of natural speech. These observations of anticorrelated signals related to speech comprehension are consistent with emerging models of cooperative roles represented by BOLD signals of opposite polarity.


The better way to determine the validity, reliability, objectivity and accuracy of measuring devices.
In relation to statistical analysis, studies to determine the validity, reliability, objectivity and precision of new measuring devices are usually incomplete, due in part to using only correlation coefficient and ignoring the data dispersion. The aim of this study was to demonstrate the best way to determine the validity, reliability, objectivity and accuracy of an electro-inclinometer or other measuring devices. Another purpose of this study is to answer the question of whether reliability and objectivity represent accuracy of measuring devices. The validity of an electro-inclinometer was examined by mechanical and geometric methods. The objectivity and reliability of the device was assessed by calculating Cronbach's alpha for repeated measurements by three raters and by measurements on the same person by mechanical goniometer and the electro-inclinometer. Measurements were performed on "hip flexion with the extended knee" and "shoulder abduction with the extended elbow." The raters measured every angle three times within an interval of two hours. The three-way ANOVA was used to determine accuracy. The results of mechanical and geometric analysis showed that validity of the electro-inclinometer was 1.00 and level of error was less than one degree. Objectivity and reliability of electro-inclinometer was 0.999, while objectivity of mechanical goniometer was in the range of 0.802 to 0.966 and the reliability was 0.760 to 0.961. For hip flexion, the difference between raters in joints angle measurement by electro-inclinometer and mechanical goniometer was 1.74 and 16.33 degree (P<0.05), respectively. The differences for shoulder abduction measurement by electro-inclinometer and goniometer were 0.35 and 4.40 degree (P<0.05). Although both the objectivity and reliability are acceptable, the results showed that measurement error was very high in the mechanical goniometer. Therefore, it can be concluded that objectivity and reliability alone cannot determine the accuracy of a device and it is preferable to use other statistical methods to compare and evaluate the accuracy of these two devices.


Stimulus secretion coupling: role of cyclic GMP and calcium in the regulation of secretion from rat exocrine pancreas.
In rat pancreatic fragments, stimulation of amylase and labeled protein release by carbachol, caerulein, and ionophore A 23187 results within minutes in a short rise in cyclic GMP levels. Cyclic AMP levels do not change significantly. The secretory response elicited by each secretagogue is not modified when combined in pairs. Under intracellular calcium depleting conditions, both the cyclic GMP and the secretory responses to secretagogues are inhibited in parallel, suggesting a good correlation between both processes. Furthermore, 8-Bromocyclic GMP induces pancreatic secretion, but to a lesser extent, and fails to alter the increase in secretion caused by the various secretagogues. However, other agents such as imidazole, ascorbic acid, phenylhydrazine, and sodium azide also increase cyclic GMP levels but fail to stimulate pancreatic secretion. On the other hand, dibutyryl cyclic AMP also stimulates amylase and labeled protein discharge and potentiates the increase caused by cabachol, caerulein, and ionophore A 23187. These results do not permit conclusions regarding a cause and effect relationship between cyclic GMP and secretion. A role for calcium seems to be the most likely.


The inhibition of HIV-1 protease by interface peptides.
Previous studies have shown that some peptides derived from one of the terminal amino acid segments of the homodimeric HIV-1 protease show moderate inhibition of this enzyme probably by interfering with the "interface" structure formed by the four terminal segments of the dimer. Different peptides, with improved inhibitory potency, were devised by computer modelling, synthesized, and tested. Ac-TVSFNF, the short peptide with the best inhibition so far (IC50 = 80 microM) is identical with the C-terminal part of the gag-pol frame shift protein p6*. This suggests a regulatory function of p6* as a dimerization inhibitor of HIV protease in the virion. Peptides derived from the active site sequence of PR are inactive. The two terminal hexapeptides of reverse transcriptase are also inactive in the HIV-1 PR activity assay.


Phonatory mechanisms after vertical partial laryngectomy with glottic reconstruction by false vocal fold flap.
A prospective randomized study was designed to compare phonatory mechanisms in patients treated with frontolateral partial laryngectomy (FLPL) with or without glottic reconstruction with false vocal fold (FVF) mucosal flap. Objective voice assessment was based on computerized acoustic recordings and videolaryngostroboscopy performed before, 1 year after, and 2 years after surgery. Phonatory mechanisms were studied according to the surgical technique and correlated with acoustic recordings. The results showed that supraglottic structures participated in laryngeal closure and voice production in 80% of cases in which a standard FLPL was performed. The FVF mucosal flap was involved in both laryngeal closure and voice production in 54% of patients treated with glottic reconstruction. The type of laryngeal closure (glottic or supraglottic) statistically influenced the acoustic measurements. As glottic closure is more frequent in patients treated with glottic reconstruction, the authors recommend performing reconstruction of the glottis with an FVF mucosal flap when an FLPL is indicated.


[Evaluation of intellectual functions in patients with Parkinson's disease. Bibliographic review].
A literature review shows that patients affected by Parkinson's disease present an intellectual impairment more frequently than the comparably aged population. Such impairment has been related to several factors (age, arteriosclerosis, motor difficulties, depression, dopaminergic therapy, cortical and/or subcortical lesions). Parkinsonian dementia may be caused by the extent of the degenerative process. Our own results show that parkinsonian patients with dementia are different from nondemented ones with the following features: a) a more marked bradykinesia b) a more severe extrapyramidal picture c) a progressive unresponsiveness to levodopa in a shorter time. It seems possible that there is a Parkinson syndrome characterized, clinically, by an intellectual impairment with a poor prognosis quoad valetudinem, and, anatomically, with multiple cortical and subcortical lesions. Such syndrome may be a "transition" form between Parkinson disease and senile-presenile dementia.


Effect of the charge balance on high-efficiency blue-phosphorescent organic light-emitting diodes.
The charge balance in blue-phosphorescent devices was studied using single-carrier devices, and the results show that the transport is highly hole dominant. The effect of the charge balance on the device performance was further demonstrated using different electron-transport materials with different electron mobilities. By optimization of the charge balance, a maximum current efficiency of 60 Cd A(-1) at a luminance of 500 cd m(-2) was achieved.


Direct innervation of white fat and adrenal medullary catecholamines mediate photoperiodic changes in body fat.
Seasonal adjustments in Siberian hamster adiposity are triggered by day length changes [i.e., short "winter-like" days (SDs) elicit body fat decreases vs. long "summer-like" days (LDs)]. These and other white adipose tissue (WAT) mass decreases traditionally have been ascribed to lipolysis triggered by sympathetically mediated, adrenal medullary released epinephrine; however, recent evidence suggests that direct sympathetic innervation of WAT also is important. Therefore, the contributions of WAT sympathetic innervation and adrenal medullary catecholamines to SD-induced decreases in adiposity were tested. Siberian hamsters were surgically bilaterally adrenal demedullated (ADMEDx) or sham ADMEDx, and all had one inguinal WAT (IWAT) pad sympathectomized via locally injected guanethidine, with the contralateral pad serving as a within-animal innervated control. One-half of the hamsters remained in LDs; the remainder was transferred to SDs. Guanethidine and ADMEDx abolished IWAT norepinephrine and adrenal epinephrine contents, respectively. Although sympathetic denervation or ADMEDx alone did not block SD-induced decreases in IWAT mass, their combination did. These results suggest that both adrenal catecholamines and the sympathetic innervation of WAT interact to decrease SD-induced decreased adiposity.


Serum testosterone levels and reference ranges in reproductive-age women.
To determine the levels of serum testosterone and dehydroepiandrosterone sulfate (DHEAS) in women with no clinical signs of hyperandrogenism and no history of glucocorticoid or oral contraceptive use and to compare these levels with the reference ranges provided by commercial laboratories. We undertook a cross-sectional retrospective study of 271 reproductive-age women encountered at an endocrinology clinic for complaints of potential thyroid problems. Serum testosterone and DHEAS levels were determined, and statistical analyses were performed. The serum testosterone level in women with no acne, hirsutism, or menstrual dysfunction was 14.1 +/- 0.9 ng/dL (mean +/- standard error of the mean) (95% confidence interval [CI] = 12.4 to 15.8). This group was considered our study reference population. In women with menstrual dysfunction but no acne or hirsutism, the mean testosterone level was significantly higher (17.9 +/- 1.1 ng/dL; 95% CI = 15.7 to 20.0; P<0.002); with mild hirsutism, it further increased (38.4 +/- 5.1 ng/dL; 95% CI = 27.4 to 49.4; P<0.005); and with moderate to severe hirsutism, it was still higher (49.0 +/- 2.3 ng/dL; 95% CI = 44.4 to 53.6; P<0.003). Serum DHEAS levels showed similar patterns. The upper limit (mean + 2 standard deviations) of testosterone in our study reference population was 28 ng/dL, a level that provided a sensitivity of 84% for detecting hyperandrogenemia. The detection of hyperandrogenemia is essentially impossible when the upper limit of the reference range for testosterone from commercial laboratories (95 ng/dL) is used. The testosterone levels reported herein and in the literature for hyperandrogenic women both are within the reference (normal) ranges provided by commercial laboratories. These observations demonstrate why diagnosis of hyperandrogenemia in hyperandrogenic women is difficult when commercial laboratories are used and why this condition is not detected in most affected women. Commercial laboratories should reevaluate the methods used for establishing their reference ranges for serum testosterone.


FACTORS ASSOCIATED WITH ODONTOGENIC BACTERAEMIA IN ORTHODONTIC PATIENTS.
Various researches have investigated factors associated with the prevalence and intensity of bacteraemia following oral procedures including orthodontic procedures. The aim of this study was to determine the effect of age, gender, plaque and gingival indices on the occurrence of odontogenic bacteraemia following orthodontic treatment procedures. Orthodontic Clinic, Lagos University Teaching Hospital (LUTH), Lagos, Nigeria. Using the consecutive, convenience sampling method, a total of 100 subjects who met the inclusion criteria were recruited for the study and peripheral blood was collected before and again within 2 minutes of completion of orthodontic procedures for microbiologic analysis using the BACTEC automated blood culture system and the lysis filtration methods of blood culturing. The subjects were randomly placed in one of four orthodontic procedures investigated: alginate impression making (Group I), separator placement (Group II), band cementation (Group III) and arch wire change (Group IV). Plaque and gingival indices were assessed using the plaque component of the Simplified Oral Hygiene Index (OHI-S) (Greene & Vermillion) and Modified gingival index (Lobene) respectively before blood collection. Spearman Point bi-serial correlations and logistic regression statistics were used for statistical evaluations at p < 0.05 level. An overall baseline prevalence of bacteraemia of 3% and 17% were observed using the BACCTEC and lysis filtration methods respectively. Similarly, overall prevalence of bacteraemia following orthodontic treatment procedures of 16% and 28% were observed respectively using the BACTEC and lysis filtration methods. A statistically significant increase in the prevalence of bateraemia was observed following separator placement (p=0.016). An increase in age, plaque index scores and modified gingival index scores of the subjects were found to be associated with an increase in the prevalence of bacteraemia following orthodontic treatment procedures, with plaque index score showing the strongest correlation. Separator placement was found to induce significantly highest level of bacteraemia. Meticulous oral hygiene practice and the use of 0.2% chlorhexidine mouth rinse prior to separator placement may be considered an effective measure in reducing oral bacteria load and consequent reduction of the occurrence of bacteraemia following orthodontic treatment procedures.


One-Step Hybrid Bending/Diffusion Bonding Process and Analysis of the Bonding Characteristics of Titanium Alloy Sheets.
A one-step hybrid bending/diffusion bonding process (HB/DBP) was developed for application to Ti-6Al-4V sheets to effectively improve buy-to-fly (BTF) ratio of aircraft parts, integrating sequential diffusion bonding followed by a bending process. The resulting bonding characteristics of these titanium alloy sheets were analyzed. Microstructural analysis and mechanical lap shear tests were performed to estimate the bonding quality. Additionally, bonding ratio, thickness strain, and shear strength were evaluated in relation to pressure under increasing temperature. When the applied pressure was lower than 0.5 MPa, early failure occurred at the joint of the specimens. However, when high pressure was applied, early failure occurred near the joint. To discuss the phenomenon, time-dependent viscoplastic material properties were characterized, and a numerical simulation analysis was performed. Viscoplastic deformation was observed around the bending area, which caused weakness around the bond under high-pressure conditions. A prototype of a Y-shaped heat shield was manufactured and the buy-to-fly ratio was effectively improved using the newly developed process. This study demonstrates the potential of applying the developed process for producing aircraft parts and the importance of viscoplastic behavior for the analysis of final product reliability.


PEGylation and its impact on the design of new protein-based medicines.
PEGylation is the covalent conjugation of PEG to therapeutic molecules. Protein PEGylation is a clinically proven approach for extending the circulation half-life and reducing the immunogenicity of protein therapeutics. Most clinically used PEGylated proteins are heterogeneous mixtures of PEG positional isomers conjugated to different residues on the protein main chain. Current research is focused to reduce product heterogeneity and to preserve bioactivity. Recent advances and possible future directions in PEGylation are described in this review. So far protein PEGylation has yielded more than 10 marketed products and in view of the lack of equally successful alternatives to extend the circulation half-life of proteins, PEGylation will still play a major role in drug delivery for many years to come.


Abnormal formation of the glucan network from regenerating protoplasts in Schizosaccharomyces pombe cps8 actin point mutant.
To study the close relationship between the actin cytoskeleton and cell wall formation, the process of cell wall formation in reverting protoplasts of the fission yeast, Schizosaccharomyces pombe, cps8 actin point mutant was investigated by ultra-high-resolution low-voltage scanning electron microscopy (UHR-LVSEM) and transmission electron microscopy (TEM). The protoplast of the cps8 mutant began to form a glucan network in a unipolar manner and to secrete alpha-galactomannan. The site of cell wall formation grew in a cylindrical shape in the wild-type protoplast. The alpha-galactomannan did not fill in the intrafibrillar spaces completely, however, and the fibrils were exposed on the cell surface. UHR-LVSEM images indicated that the glucan fibrils were thin and rope-shaped, forming a looser network than the wild-type. TEM images indicated the finest fibrils were approximately 1.5 nm in diameter, the same diameter as the wild-type. These results suggest that the cps8 mutant was insufficient in developing cross-linkage with the glucan fibrils up to the wide ribbon shape as found in the wild-type [Osumi M et al. (1989) J. Electron Microsc. 38: 457-468; Osumi M (1998) Micron 29: 207-233]. These findings appear to indicate that the actin cytoskeleton controls formation of the glucan network and secretion of beta-1,6-glucan, and confirm the close relationship of the actin cytoskeleton and glucan formation.


Differential characteristics of bipolar I and II disorders: a retrospective, cross-sectional evaluation of clinical features, illness course, and response to treatment.
The distinction between bipolar I and bipolar II disorder and its treatment implications have been a matter of ongoing debate. The aim of this study was to examine differences between patients with bipolar I and II disorders with particular emphasis on the early phases of the disorders. 808 subjects diagnosed with bipolar I (N = 587) or bipolar II disorder (N = 221) according to DSM-IV criteria were recruited between April 1994 and March 2022 from tertiary-level mood disorder clinics. Sociodemographic and clinical variables concerning psychiatric and medical comorbidities, family history, illness course, suicidal behavior, and response to treatment were compared between the bipolar disorder types. Bipolar II disorder patients were more frequently women, older, married or widowed. Bipolar II disorder was associated with later "bipolar" presentation, higher age at first (hypo)mania and treatment, less frequent referral after a single episode, and more episodes before lithium treatment. A higher proportion of first-degree relatives of bipolar II patients were affected by major depression and anxiety disorders. The course of bipolar II disorder was typically characterized by depressive onset, early depressive episodes, multiple depressive recurrences, and depressive predominant polarity; less often by (hypo)mania or (hypo)mania-depression cycles at onset or during the early course. The lifetime clinical course was more frequently rated as chronic fluctuating than episodic. More patients with bipolar II disorder had a history of rapid cycling and/or high number of episodes. Mood stabilizers and antipsychotics were prescribed less frequently during the early course of bipolar II disorder, while antidepressants were more common. We found no differences in global functioning, lifetime suicide attempts, family history of suicide, age at onset of mood disorders and depressive episodes, and lithium response. Differences between bipolar I and II disorders are not limited to the severity of (hypo)manic syndromes but include patterns of clinical course and family history. Caution in the use of potentially mood-destabilizing agents is warranted during the early course of bipolar II disorder.


On the heating of inductively coupled resonators (stents) during MRI examinations.
Stents that have been implanted to preserve the results of vascular dilatation are frequently affected by in-stent restenosis, which ideally should be followed up by a noninvasive diagnostic modality. Active MRI stents can enable this kind of follow-up, while normal metallic stents can not. The prototype stents investigated in this study were designed as electric resonating circuits without a direct connection to the MR imager, and function as inductively coupled transmit coils. The model of a long solenoid coil is used to describe the additional power loss caused by such resonators. The theoretically estimated temperature increase is verified by measurements for different resonators and discussed for worst-case conditions. The RF power absorption of an active resonator is negligible compared to the total power absorbed during MRI. The local temperature increase observed for prototypes embedded in phantoms is in a range that excludes direct tissue damage. However, ruptures in the conducting structure of a resonator can cause hot spots, which may establish a high local temperature. This hazard can be reduced by designing resonators with a low quality (Q) factor or by setting the circuit slightly off resonance; however, this would lower the nominal amplification for which the resonator was designed.


Detection of Echinococcus multilocularis in foxes: evaluation of a protocol of the intestinal scraping technique.
The intestinal scraping technique (IST) is widely used for the detection of definitive hosts infected with Echinococcus multilocularis. The sensitivity of the method has been questioned in recent years. Several variations of the technique are used that may differ in their performance. We therefore estimated the diagnostic sensitivity and specificity of the IST protocol used in our lab by examining the small intestines of 210 E. multilocularis-infected foxes and 294 foxes that had tested negative for this parasite. To this end, IST was first performed on 48 and 294 intestines from infected and uninfected foxes respectively, followed by an examination of the entire remaining mucosa of the small intestine to discover any infections with E. multilocularis that had not been detected by IST. The point estimate for diagnostic sensitivity was 100%. Five different classes of infection intensities were formed. The lower limits of the 95% confidence intervals ranged between 76.8% and 92.6% depending on the number of samples analysed per class. When the small intestines of another 162 infected foxes were examined by IST and the results recorded separately for the anterior, middle and posterior third of the small intestine, a strong preference of E. multilocularis for the posterior third was observed. For epidemiological purposes, it may thus be possible to restrict routine investigations to the posterior portion of the small intestine. By contrast, a reduction of the number of slides examined per infected animal may lead to a considerable loss in sensitivity in animals with a low intensity of infection.


Learning and change among leaders of a professional nursing association.
This is a report of the results of a qualitative research study that investigated the informal learning and changes experienced by 20 members of an exemplary chapter of critical care nurses as they advanced from being new members to becoming officers and board members. Qualitative research methods were used that included analysis of critical incidents, documents, and individual interviews. Methods used, results of the study, and conclusions and recommendations are discussed.


Systematic Review of Topical Hemostatic Agent Use in Minimally Invasive Gynecologic Surgery.
To perform a systematic review of articles evaluating hemostatic effectiveness and peri-operative outcomes when topical hemostatic agents (HA) are used in minimally invasive gynecologic surgeries (MIGS) for benign conditions. Studies published through March 31, 2017 were retrieved through PubMed, EMBASE, Cochrane, and ClinicalTrials.gov to identify all eligible studies. No studies were excluded based on publish date. All comparative studies or case series with >10 participants reporting use of at least one topical HA in MIGS for benign conditions were included as long as full-text articles were available and written in English. Studies were excluded if surgery was done for malignancy or completed via an open approach. Articles that included multiple surgical subspecialties were excluded if data related to MIGS was unable to be isolated. Evaluation for eligibility and data extraction was performed by three independent reviewers. Quality of evidence was also assessed by each reviewer. From 132 articles, a total of 8 studies were included in this systematic review. We found that use of fibrin sealant decreased time to hemostasis, postoperative hemoglobin drop, and estimated blood loss (EBL) compared with bipolar energy and reduced the overall operative time in laparoscopic myomectomy. When fibrin sealant use at time of myomectomy was compared to bipolar energy there was no significant difference in the rate of postoperative complications. Furthermore, there was less of a decrease in anti-Mullerian hormone (AMH) level when a thrombin-gelatin matrix was used compared to bipolar energy on ovarian tissue. Application of topical HA in MIGS can reduce operative time, blood loss, and ameliorate damage to ovarian function. However, more data needs to be gathered for use of HA during different types of gynecologic procedures (adnexal surgery, myomectomy, and hysterectomy) to provide better quality evidence to guide their use.


N-Terminal Methionine Processing.
Protein synthesis is initiated by methionine in eukaryotes and by formylmethionine in prokaryotes. N-terminal methionine can be co-translationally cleaved by the enzyme methionine aminopeptidase (MAP). When recombinant proteins are expressed in bacterial and mammalian expression systems, there is a simple universal rule that predicts whether the initiating methionine will be processed by MAP based on the size of the residue adjacent (penultimate) to the N-methionine. In general, if the side chains of the penultimate residues have a radius of gyration of 1.29 Å or less, methionine is cleaved. © 2017 by John Wiley & Sons, Inc.


Effects of pitch accent position, type, and status on focus projection.
This paper examines predictions made by two theories of the relationship between pitch accent and focus. The empirical evidence presented suggests that listeners are sensitive to a variety of factors that may affect the focus projection ability of pitch accents, that is the ability of a pitch accent on one word to mark focus on a larger constituent. The findings suggest that listeners' interpretation of focus structure is most sensitive to the presence or absence of a pitch accent on a focused constituent and the deaccenting of following unfocused material (pitch accent position). Preliminary evidence suggests that the status of a pitch accent as nuclear or prenuclear may also affect listeners' interpretations, though to a lesser extent than accent position. Finally, the results show that focus projection is affected only minimally, if at all, by the type of pitch accent (at least for the two accent types compared (H* vs. L + H*)).


Physiological and analgesic effects of continuous-rate infusion of morphine, butorphanol, tramadol or methadone in horses with lipopolysaccharide (LPS)-induced carpal synovitis.
Continuous-rate infusion (CRI) of drugs results in more stable plasma drug concentrations than administration of intermittent boluses, thus providing greater stability of physiological parameters. The aim of this study was to evaluate the physiologic and analgesic effects of the administration of morphine, butorphanol, tramadol or methadone by CRI in horses with induced synovitis of the radiocarpal joint. Increased values of cardiorespiratory parameters and body temperature were observed in all groups after initiation of opioid administration, and these increases were sustained throughout the CRI period. Morphine, butorphanol and methadone each caused a reduction in gut sounds, and this effect was greatest in animals that received morphine. Administration of morphine or methadone reduced the degree of lameness after the end of intravenous infusion. Administration of tramadol did not alter the degree of lameness in the animals. CRI of morphine or methadone, but not butorphanol or tramadol, provided analgesia in horses with carpal synovitis. All of these opioids increased cardiovascular and respiratory parameters and reduced gut sounds during CRI.


Metabolic Stress and Compromised Identity of Pancreatic Beta Cells.
Beta cell failure is a central feature of type 2 diabetes (T2D), but the molecular underpinnings of the process remain only partly understood. It has been suggested that beta cell failure in T2D involves massive cell death. Other studies ascribe beta cell failure to cell exhaustion, due to chronic oxidative or endoplasmic reticulum stress leading to cellular dysfunction. More recently it was proposed that beta cells in T2D may lose their differentiated identity, possibly even gaining features of other islet cell types. The loss of beta cell identity appears to be driven by glucotoxicity inhibiting the activity of key beta cell transcription factors including Pdx1, Nkx6.1, MafA and Pax6, thereby silencing beta cell genes and derepressing alternative islet cell genes. The loss of beta cell identity is at least partly reversible upon normalization of glycemia, with implications for the reversibility of T2D, although it is not known if beta cell failure reaches eventually a point of no return. In this review we discuss current evidence for metabolism-driven compromised beta cell identity, key knowledge gaps and opportunities for utility in the treatment of T2D.


How Understanding the Role of an Additive Can Lead to an Improved Synthetic Protocol without an Additive: Organocatalytic Synthesis of Chiral Diarylmethyl Alkynes.
The use of additives for organic synthesis has become a common tactic to improve the outcome of organic reactions. Herein, by using an organocatalytic process for the synthesis of chiral diarylmethyl alkynes as a platform, we describe how an additive is involved in the improvement of the process. The evolution of an excellent synthetic protocol has been achieved in three stages, from 1) initially no catalyst turnover, to 2) good conversion and enantioselectivity with a superior additive, and eventually 3) even better efficiency and selectivity without an additive. This study is an important and rare demonstration that understanding the role of additive can be so beneficial as to obviate the need for the additive.


Development and Psychometric Properties of a Condom Use and Its Cognitive Determinants Questionnaire (CUCDQ).
The aim of this study was to assess the psychometric properties of Condom Use and its Cognitive Determinants Questionnaire (CUCDQ) among married women in Tabriz, Iran. In this cross-sectional study, applying multistage cluster sampling 388 married women were recruited to participate in the study. A comprehensive literature review was conducted to develop CUCDQ. Face, content, and construct validity, as well as reliability, were investigated. Principal component factor analysis with varimax rotation demonstrated a six factors structure as the best solution [Bartlett's Test of Sphericity (Approx. Chi-Square= 4193.07, df= 780, p<0.001); KMO= 0.815] which explained 43.13% of all the variance between the items. CUCDQ represented a proper validity, reliability, simplicity and functionality. CUCDQ may be helpful for family health care providers and family planning decision makers in precise assessing the behavioural, psychological, and educational factors related to condom use. This scale may be useful in a various range of studies including family planning or STIs prevention studies in different communities. Future research is recommended to assess the different dimensions of the tool in different communities.


Structural and functional characterization of the human brain D-aspartate oxidase.
D-Aspartate oxidase (DDO) cDNAs were isolated from the human brain RNA using the RT-PCR method. Two forms (DDO-1 and DDO-2) of DDO mRNA were detected. Structural analysis of the DDO cDNAs and genomic DNA showed that DDO-1 and DDO-2 are produced by alternative splicing from a single gene. A protein encoded by the DDO-1 cDNA consists of 341 amino acids, and the amino acid sequence of DDO-2 was identical to that of DDO-1 except for the absence of 59 amino acids covering residues 95-153 of DDO-1. A homogenous preparation of DDO-1 was obtained using an expression system in Escherichia coli. DDO-1 selectively catalyzed the oxidative deamination of D-aspartate and its N-methylated derivative, N-methyl D-aspartate; the values of K(m) and k(cat) for D-aspartate were 2.7 mM and 52.5 mol D-aspartate oxidized x s(-1) x mol(-1) and those for N-methyl D-aspartate were 6.8 mM and 37.7 mol N-methyl D-aspartate oxidized x s(-1) x mol(-1), respectively.


Physical activity and cardiovascular disease.
This review, based on prospective epidemiological studies, indicates the existence of a dose-response relationship between physical activity and coronary heart disease (CHD), which is linear at least up to a certain level of activity. Leisure time physical activity is associated with about a 30-50% reduction in risk of CHD. The benefit of leisure-time physical activity is seen in both men and women, in middle-aged and older subjects and in men with established CHD. Several mechanisms, which could contribute to the protective effect of physical activity on CHD have been identified. Prospective studies suggest that physical activity is also associated with reduced risk of stroke. Overall, the evidence points to the benefit of continued regular moderate physical activity which does not need to be vigorous or sporting, and includes activities such as walking or gardening, readily attainable by large sections of the population. Current evidence supports the recommended guidelines of 30 minutes of moderate physical activity on most days of the week in both primary and secondary prevention of CHD.


Temporary partially-covered metal stent insertion in benign esophageal stricture.
To study the therapeutic efficacy of temporary partially-covered metal stent insertion on benign esophageal stricture. Temporary partially-covered metal stent was inserted in 83 patients with benign esophageal stricture. All the patients had various dysphagia scores. Insertion of 85 temporary partially-covered metal stents was performed successfully in 83 patients with benign esophageal stricture and dysphagia was effectively remitted in all the 83 cases. The dysphagia score was 3.20+/-0.63 (mean+/-SD) and 0.68+/-0.31 before and after stent insertion, and 0.86+/-0.48 after stent removal. The mean diameter of the strictured esophageal lumen was 3.37+/-1.23 mm and 25.77+/-3.89 mm before and after stent insertion, and 16.15+/-2.96 mm after stent removal. Follow-up time was from 1 week to 96 months (mean 54.26+/-12.75 months). The complications were chest pain (n=37) after stent insertion, and bleeding (n=12) and reflux (n=13) after stent removal. Temporary partially-covered metal stent insertion is one of the best methods for treatment of benign esophageal stricture.


Dental fluorosis among participants in a non-supervised fluoride tablet program.
The aim of the present study was to describe the intraoral pattern of dental fluorosis among fluoride tablet consumers. One hundred and forty-two children, of whom 56 had participated in a fluoride tablet program of 0.5/1.0 mg NaF per day were examined blindly for possible fluoride-induced enamel changes. A low prevalence of dental fluorosis was found among non-participants. The later in life the tooth was formed, the higher was the prevalence. The subjects who had participated in the fluoride tablet program showed a significantly higher prevalence of fluorosis. They could be divided into three groups: Group 1 exhibited a tooth prevalence pattern not statistically different from that of the non-participants, group 2 showed dental fluorosis in almost all teeth except in those formed before the start of the tablet program. In group 3 the early and the late formed teeth showed very little fluorosis while those formed in the few years just after the initiation of the fluoride tablet intake were affected by fluorosis.


The Louisiana Medicare payments of Part A and B.
Current health system reform efforts are based on the notion that the government can best design a cost efficient system. The government already operates several health care systems, including Medicare and Medicaid. Despite the development of a plethora of cost-control initiatives, such as price-fixing, utilization and peer review, and Diagnostic Related Groups, the government has been unable to control the burgeoning costs of these programs. Health system reform efforts appear directed toward the expansion of many of these same failed efforts. Only by first evaluating where the money goes can real efforts at improving the economics of the system--without jeopardizing quality of care--be successful. The author has examined the Louisiana Medicaid program in a previous article. This article examines the function and expenditures of the Louisiana Medicare program: Part B, the "physician's component" and Part A, the "hospital component."


[Effect of Kansui Radix stir-fried with vinegar on fecal metabolomics in Walker-256 rats with ascites].
Utilizing metabolomics technology, this study explored the change of fecal endogenous metabolites in Walker-256 rats with malignant ascites after the administration with Kansui Radix(KR) stir-fried with vinegar(VKR), sought the potential biomarkers in feces which were related to the treatment of malignant ascites by VKR and revealed the biological mechanism of water-expelling effect of VKR. Ultra-fast liquid chromatography-quadrupole-time-of-flight mass spectrometry(UFLC-Q-TOF-MS) was employed to detect the feces of rats in all groups. Principle component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were conducted to achieve pattern recognition. Combining t-test and variable importance in the projection(VIP) enabled the screening of potential biomarkers for the malignant ascites. Metabolic pathway analysis was accomplished with MetaboAnalyst. Correlation analysis was finally conducted integrating the sequencing data of gut microbiota to elucidate the mechanism underlying the water-expelling effect of VKR. The results showed that both KR and VKR could restore the abnormal metabolism of model rats to some extent, with VKR being inferior to KR in the regulation. Eleven potential biomarkers were identified to be correlated with the malignant ascites and five metabolic pathways were then enriched. Four kinds of gut microbiota were significantly related to the potential biomarkers. The water-expelling effect of VKR may be associated with the regulation of phenylalanine metabolism, biosynthesis of phenylalanine, tyrosine and tryptophan, tryptophan metabolism, glycerophospholipid metabolism, and glycosylphosphatidylinositol(GPI)-anchor biosynthesis. This study can provide a scientific basis for comprehensive understandings of the interaction between gut microbiota and host which has relation to the water-expelling effect of VKR and guide the reasonable clinical application of VKR.


Extent of Resection, Visual, and Endocrinologic Outcomes for Endoscopic Endonasal Surgery for Recurrent Pituitary Adenomas.
To assess outcomes after endoscopic endonasal surgery for recurrent or residual pituitary adenomas. We retrospectively analyzed 61 patients from 2009 to 2016 who underwent endoscopic endonasal surgery for recurrent or residual pituitary adenomas after previous microscopic or endoscopic transsphenoidal operation. The previous surgical approach was endoscopic endonasal in 55.7% and microscopic in 44.2% of patients. The mean preoperative maximal tumor diameter was 2.3 cm. Tumor commonly invaded the suprasellar cistern (63.9%). Gross total resection (GTR) was achieved in 31 patients (51.7%). GTR rate was 68.4% and 21.7% for Knosp grade 0-2 and grade 3-4 tumors, respectively (P < 0.001). GTR was 73.1% and 35.3% for patients with previous microscopic and endoscopic transsphenoidal surgery, respectively (P = 0.002). On multivariate analysis, smaller tumor size (odds ratio [OR], 1.1 per cm; P = 0.007), Knosp grade 0-2 (OR, 9.7; P = 0.002), and previous microscopic approach (OR, 12.7; P = 0.007) were independent predictors of GTR. Preoperative visual deficit outcome was improved in 32.5%, unchanged in 62.5%, and worse in 5.0%. New postoperative endocrinopathies included adrenal insufficiency (6.5%), hypothyroidism (8.1%), hypogonadism (6.5%), and diabetes insipidus (4.9%). Complications included postoperative cerebrospinal fluid leak (4.9%), meningitis (1.6%), medical complications (4.9%), and postoperative hematoma requiring re-exploration (3.2%). The endoscopic endonasal approach provides a safe and effective option for recurrent pituitary adenomas. Smaller tumor size, absence of cavernous sinus invasion, and previous microscopic approach were independent predictors of GTR. This finding might suggest that inadequate exposure or limited viewing angle may adversely affect extent of resection in primary microscopic surgeries.


Long-Term Adverse Effects of Early Growth Acceleration or Catch-Up Growth.
Whilst prevention of growth faltering has both short- and long-term health benefits, whether too fast or accelerated infant growth adversely affects later health outcomes is controversial and a major focus of research. Many observational studies suggest that rapid weight gain in infancy (upward centile crossing) increases the long-term risk of obesity and non-communicable disease. This association has been seen in infants from low- and high-income countries, in infants born preterm or at term, and those born with normal or low birth weight for gestation. Experimental (randomized) studies in both breast- and formula-fed infants support a causal link between early growth acceleration and infant nutrition and later risk of obesity. These observations suggest that strategies to optimize the pattern of infant growth could make a major contribution to stemming the current global epidemic of non-communicable disease. Key Messages: The optimal pattern of infant weight gain is likely to differ in different populations. The benefits of rapid infant weight gain for later neurodevelopment favors the promotion of rapid growth in infants born preterm. However, growth acceleration in healthy infants born at term (either normal or low birth weight for gestation) is likely to have adverse effects for long-term health.


A biophysical characterization of the peptide drug pramlintide (AC137) using empirical phase diagrams.
AC137 (pramlintide) is a 37-residue peptide analogue of the hormone amylin. Pramlintide has been studied as an adjunct antihyperglycemic treatment for patients with type 2 or type 1 diabetes who use insulin. This study took an empirical phase diagram (EPD) approach to obtain information about the structural stability of this peptide by compiling thermal perturbation data acquired from multiple spectroscopic methods, including high-resolution second-derivative UV absorbance spectroscopy, optical density, fluorescence, and circular dichroism. This approach enabled us to accomplish two major goals: (1) characterize the structure and physical stability of AC137 and (2) assess the application of EPDs to a small peptide. Results obtained at low concentration of AC137 revealed a peptide with ill-defined structure and insensitivity to pH. Use of isotope exchange NMR confirmed this lack of structure. At the current formulation of pH 4, AC137 exhibited stability at concentrations of 1.8 to 8.8 mg/mL. High concentrations of the peptide showed a tendency to aggregate at pH 6-7.5. Construction of EPDs under the various experimental conditions examined manifested color changes that correlated well with the raw data. The utility and limitations of the EPD approach when applied to weakly structured peptides are discussed.


Subcutaneous emphysema after tonsillectomy: a case report.
We experienced a case of a subcutaneous emphysema after tonsillectomy. The patient, a 24-year-old man, complained of a recurrent sore throat and was diagnosed as having chronic tonsillitis. Pre-operative general examinations revealed no abnormalities. The operation was carried out under general anesthesia. The adhesions between the tonsils and the surrounding tissues were moderate. The bi-lateral tonsils were easily removed. The recovery period was uneventful. On the next morning, marked swelling of the left cheek and submandibular area was noted. On palpation, there was a characteristic crepitation and softness in these areas. The X-ray examination revealed subcutaneous emphysema. There was no finding of airway obstruction. We diagnosed him as having a subcutaneous emphysema and administered antibiotics for 5 days. From clinical findings, the subcutaneous emphysema was thought to be caused by surgical rather than anesthetic factors. The subcutaneous emphysema gradually disappeared. One year after the tonsillectomy, the patient is under observation as an outpatient and is free from any abnormal symptoms. To avoid this kind of complication, we should pay attention to carefully separate the tonsil from its fossa and to make appropriate selection of surgical equipments.


Reentry interventions that address substance use: A systematic review.
Justice-involved individuals with substance use problems have heightened risk of relapse and recidivism after release from incarceration, making reentry a critical time to provide evidence-based treatments (EBTs) for substance use; however, the extent to which reentry interventions incorporate EBTs for substance use is unclear. This systematic review identified studies of reentry interventions in the past 10 years that address substance use, assessed whether EBTs were used, and explored which interventions were effective in reducing substance use and recidivism postrelease. Eligible studies included interventions that began during incarceration and continued postrelease or began within 3 months of release and addressed substance use in some capacity. One hundred twelve full text articles were reviewed and 38 met inclusion criteria, representing 34 unique interventions. Of the 34 interventions, 21 provided substance use treatment whereas 13 facilitated connections to treatment. Of the 21 interventions providing treatment, the primary modalities were cognitive-behavioral therapy (n = 6), motivational interviewing (n = 2), medication assisted treatment (n = 2), therapeutic community (n = 2), psychoeducation or 12-step (n = 5), and four did not specify the modality. Of the 31 studies that assessed recidivism outcomes, 18 found reduced recidivism for the treatment group on at least one indicator (e.g., rearrest, reincarceration). Of the 13 studies that assessed substance use outcomes, 7 found reduced substance use for the treatment group on at least one indicator. Results were not consistent for any particular treatment approach or modality and highlight the need for consistent integration of EBTs for substance use into reentry interventions. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Nationwide survey on current management strategies of toddler's fractures.
Tibial fractures are common in children less than 3 years old. The traditional management involves immobilization in an above knee cast for both confirmed (positive x-ray) and presumed (normal x-ray) toddler's fractures. This carries health care implications and causes unnecessary burden for patients and their families. There is a paucity of literature describing the ideal immobilization strategy for this injury. To determine: 1) the variation between Canadian emergency departments in management of toddler's fractures; 2) the variation in management between confirmed and presumed toddler's fractures; 3) the association between demographic variables and immobilization strategies. This was an email survey of all members of the Pediatric Emergency Research Canada network. The survey consisted of 2 clinical vignettes followed by multiple-choice questions. Survey response rate was 73% (153/211). For confirmed toddler's fractures, 39% of physicians chose to immobilize with above knee circumferential cast, 27% with below knee circumferential cast and 20% with below knee splint. For presumed toddler's fractures, 44% of respondents chose to manage without casting, 22% with below knee splint and 14% with above knee circumferential cast. There was significant practice variation between Canadian pediatric emergency departments for both types of fractures and between the management of confirmed and presumed toddler's fractures. Our study is the first to identify nationwide variation in the management of toddler's fractures. This variation highlights the need for future research to compare the different management strategies to determine families' preferences and functional outcomes in children with these injuries.


[Effectiveness of extracorporeal ultraviolet blood irradiation in patients with chronic obstructive bronchitis].
The use of extracorporeal ultraviolet blood radiation (EUVBR) in the treatment of 67 patients with chronic obstructive bronchitis (COB) showed some specific features of the clinical course of bacterial complications of the basic process. With EUVBR, most patients exhibited normal temperatures, less signs of intoxication and coughing, and rare rale in the lung than in the controls. A most objective criterion for the efficiency of EUVBR was a marked increase in the forced expiratory volume per sec after the first 3 procedures, which improved the patients' condition, diminished exercise-induced dyspnea. The hemogram of the patients undergone EUVBR in combination with antibiotic therapy indicated a substantial drop in erythrocyte sedimentation rates following the first 3 procedures. The growth of pathogenic and opportunistic microbes from the sputum showed a great (10-fold) reduction when EUVBR and antibiotic therapy were concurrently used. The findings suggest that EUVBR has high therapeutical benefits in the treatment of COB.


Survival and late effects in children with Hodgkin's lymphoma treated with MOPP/ABV and low-dose, extended-field irradiation.
Reduced-intensity protocols for pediatric Hodgkin's lymphoma are aimed at preserving excellent relapse-free survival while decreasing the incidence of late effects. We retrospectively reviewed the outcome of 123 children treated consecutively for Hodgkin's lymphoma at a single institution. Patients with stages I-IIIB disease received three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/ doxorubicin, bleomycin, and vinblastine (ABV) followed by 15 Gy of extended-field irradiation, while those with stage IV disease were treated with six to eight cycles of MOPP/ABV chemotherapy with or without radiotherapy. At a median follow-up of 8.5 years (range, 1.4 to 15.5 years), the estimated 10-year overall survival and event-free survival are 94% (SE, 2.2%) and 88% (SE, 3.1%) respectively. There have been 12 treatment failures and six disease-related deaths. A very large mediastinal mass ( 50% of the maximal thoracic diameter) was associated with a 10-year event-free survival of 50% (SE, 14%) compared with 91% (SE, 4.0%) for smaller masses (P < .001). Late cardiopulmonary toxicity is largely absent, and the incidence of hypothyroidism is 14%. There have been no cases of secondary leukemia and four secondary solid malignancies observed to date. MOPP/ABV and low-dose, extended-field radiotherapy is an effective treatment for pediatric Hodgkin's lymphoma. With median follow-up of 8.5 years, late cardiopulmonary effects and secondary malignancies from this treatment regimen are infrequent. Continued longitudinal observations, particularly for breast cancer in female patients and gonadotoxicity, will determine whether the goal of decreasing treatment-related complications while maintaining excellent survival has been achieved.


Realization of a quantum walk with one and two trapped ions.
We experimentally demonstrate a quantum walk on a line in phase space using one and two trapped ions. A walk with up to 23 steps is realized by subjecting an ion to state-dependent displacement operations interleaved with quantum coin tossing operations. To analyze the ion's motional state after each step we apply a technique that directly maps the probability density distribution onto the ion's internal state. The measured probability distributions and the position's second moment clearly show the nonclassical character of the quantum walk. To further highlight the difference between the classical (random) and the quantum walk, we demonstrate the reversibility of the latter. Finally, we extend the quantum walk by using two ions, giving the walker the additional possibility to stay instead of taking a step.


[Early results in the initial 15 cases of laparoscopic radical prostatectomy in Akita University Medical Center].
We herein report our experience and early results of laparoscopic radical prostatectomy in 15 cases of localized prostate cancer (11 T1c and 4 T2a tumors) performed between March 2000 and October 2001. The operative procedure was almost identical to the Montsouris technique. Conversion to the open procedure was required only in the first case because of a widely opened bladder neck that involved the ureteral orifice. No severe intraoperative or postoperative complications were observed. The mean operating time and blood loss was 383 minutes and 640 ml including intraoperative urine, respectively. Only one patient required blood transfusion. All 14 patients with a successful procedure could take fluid and walk freely on postoperative day 1. Twelve (86%) of the 14 patients could take food on postoperative day 1 and a Foley catheter was successfully removed on day 6 to 8 in 12 (86%) cases. Histologically, positive surgical margin was observed in 5 (33%) cases and all of them were considered non-organ confined (pT3 or more). Without adjuvant hormonal therapy, biochemical (PSA) failure was observed in 5 (36%) cases (median follow-up period: 11 months). Continence has been well maintained in 12 patients with no need for a pad by 3 months postoperatively and 2 patients are using only 1 pad/day for caution's sake. In terms of early postoperative recovery, intraoperative blood loss and maintenance of continence, laparoscopic radical prostatectomy may give a satisfactory result. Although long-term follow-up is required to assess disease control and maintenance of sexual function, laparoscopic radical prostatectomy may become an alternative for the treatment of organ-confined prostate cancer.


[Phase variations of Francisella tularensis lipopolysaccharide in human infection and immunization].
The comparative study of the specificity of antibodies in human sera after tularemia infection and immunization with live tularemia infection was carried out with the use of passive hemagglutination and immunoblotting techniques. The sera of tularemia patients contained two different types of immunoglobulins: strictly specific to the antigenic epitopes of F. tularensis Iipopolysaccharide (LPS) and strictly specific to F. tularensis subsp. novicida LPS. Such phenomenon may be due to phase variations of the antigenic structure of F. tularensis LPS in the body of a slightly susceptible host. The immune sera of vaccinated were found to contain antibodies, strictly specific only to F. tularensis LPS. At the same time in one vaccinee by the presence of pronounced postvaccinal reactions was found sharply defined interaction between serum imunoglobulins and F. tularensis subsp. novicida LPS. As the result, the data on the possibility of the antigenic modification of F. tularensis in tularemia infection in humans were obtained. At the same time antigenic epitopes, characteristic of faintly pathogenic and closely related F. tularensis novicida LPS, appeared in the structure of F. tularensis LPS.


Genome-Wide Analysis of Tar Spot Complex Resistance in Maize Using Genotyping-by-Sequencing SNPs and Whole-Genome Prediction.
Tar spot complex (TSC) is one of the most destructive foliar diseases of maize ( L.) in tropical and subtropical areas of Central and South America, causing significant grain yield losses when weather conditions are conducive. To dissect the genetic architecture of TSC resistance in maize, association mapping, in conjunction with linkage mapping, was conducted on an association-mapping panel and three biparental doubled-haploid (DH) populations using genotyping-by-sequencing (GBS) single-nucleotide polymorphisms (SNPs). Association mapping revealed four quantitative trait loci (QTL) on chromosome 2, 3, 7, and 8. All the QTL, except for the one on chromosome 3, were further validated by linkage mapping in different genetic backgrounds. Additional QTL were identified by linkage mapping alone. A major QTL located on bin 8.03 was consistently detected with the largest phenotypic explained variation: 13% in association-mapping analysis and 13.18 to 43.31% in linkage-mapping analysis. These results indicated that TSC resistance in maize was controlled by a major QTL located on bin 8.03 and several minor QTL with smaller effects on other chromosomes. Genomic prediction results showed moderate-to-high prediction accuracies in different populations using various training population sizes and marker densities. Prediction accuracy of TSC resistance was >0.50 when half of the population was included into the training set and 500 to 1,000 SNPs were used for prediction. Information obtained from this study can be used for developing functional molecular markers for marker-assisted selection (MAS) and for implementing genomic selection (GS) to improve TSC resistance in tropical maize.


Potential Pharmacological Inhibitors of Pim Kinase Under Clinical Trials.
Pim kinases, also known as Serine/Threonine kinases, are intensively studied protein drug targets in cancer research. They play crucial role in the regulation of signal transduction cascades that promote cell survival, proliferation and drug resistance. Pim kinases are overexpressed in several hematopoietic and solid tumors and support in vitro/in vivo malignant cell growth and survival, through cell cycle regulation and inhibition of apoptosis. Pim kinases do not have an identified regulatory domain, as they are constitutively active. They appear to be critical downstream effectors of a number of oncoproteins. When overexpressed, they mediate drug resistance to agents such as Rapamycin. X-ray crystallographic studies reveal that unlike other kinases, Pim kinases have a hinge region, which forms a unique binding pocket for ATP, offering a target for a large number of potent small-molecule Pim kinase inhibitors. Combination therapy of Pim kinase inhibitors with chemotherapeutic and other kinase modulators seems to produce an additive cytotoxic effect in cancer cells. Though clinical trials have been carried out on the first Pim inhibitory agent, SGI-1776, no concept data could be generated due to its early withdrawal. However, it has helped in accelerating the discovery of several novel Pim inhibitors in recent years. Current research on Pim kinase is expected to lead to a new generation of potent Pim kinase inhibitors with appropriate pharmacological profiles suitable for human cancer therapy in the near future. Herein, we review the synthetic route and mechanistical studies of Pim kinase inhibitors which are currently in human trials.


Endurance training effects on neurotransmitter release in rat striatum: an in vivo microdialysis study.
In the present study we use the in vivo microdialysis sampling technique to register extracellular levels of neurotransmitters in the striatum of trained and untrained rats. We further evaluate the influence of 1 h of exercise on the striatal release of dopamine (DA), noradrenaline (NA), glutamate (GLU) and gamma-aminobutyric acid (GABA) in trained and untrained rats. Male Wistars were randomly assigned to a training or control group. The exercise training consisted of running on a treadmill for 6 weeks, 5 days week-1, with running time and speed gradually increased from 30 min at 19 m min-1 during the first week to 80 min at 26 m min-1 during the final training week. The animals of the control group were placed on the treadmill twice a week, and received a total of four 'adaptation sessions', in which they exercised 15-45 min at 26 m min-1. Brain dialysates were analysed with microbore liquid chromatography (LC), with electrochemical detection (monoamines and GABA) and fluorescence detection (GLU). Soleus citrate synthase and basal striatal concentrations of DA, NA and GLU were significantly different between the trained and control animals. Sixty minutes of exercise significantly increased extracellular DA, NA and GLU levels in both groups, but there was no statistically significant difference in the exercise-induced increase between trained and control animals. There was no statistical difference in basal or exercise-induced GABA levels between trained and control animals. The results indicate that exercise training appears to result in diminished basal activity of striatal neurotransmitters, while maintaining the necessary sensitivity for responses to acute exercise.


A study of the small spherical high density lipoproteins of patients afflicted with familial lecithin: cholesterol acyltransferase deficiency.
We studied the effects of the lecithin:cholesterol acyltransferase reaction on the size and composition of the small spherical high density lipoproteins of patients afflicted with familial lecithin:cholesterol acyltransferase deficiency. We isolated these lipoproteins by preparative ultracentrifugation and rate zonal ultracentrifugation, determined their diameter by gradient gel electrophoresis, and then calculated their composition by relating measurements of their lipid and apolipoprotein content to particle volume. Our results revealed lipoprotein particles 6.0-6.2 nm in diameter that contained approximately 2 molecules of apolipoprotein A-I, 37-38 molecules of phospholipid, 3-9 molecules of unesterified cholesterol, 1-2 molecules of cholesteryl ester, and 1-2 molecules of triacylglycerol. Upon being incubated with lecithin:cholesterol acyltransferase and a source of additional unesterified cholesterol, these lipoproteins increased in content of total cholesterol and in particle size to form discrete lipoprotein products 6.6-8.6 nm in diameter. The increase in size occurred despite a net decrease in product unesterified cholesterol and phospholipid and though the net change in total lipid volume was small. Moreover, specific product lipoproteins, isolated by rate zonal ultracentrifugation, contained an increased amount of apolipoprotein A-I. These results seem best explained by a process involving lecithin:cholesterol acyltransferase-induced particle rearrangement reactions. The possibility that a similar process normally occurs in vivo deserves to be explored.


[A brief update on avian influenza and the protection of workers in view of the implementation of the new EU directive].
Influenza virus A(H5N1), since its first appearance in Hong Kong in 1997 killing six people, has continuously recorder by 2003 both new cases and deaths between these. Although the media and social attention received in the years between 2006 and 2008, mainly in Italy is not currently present, the same is not true for the avian flu that still exists in some countries. At the regulatory level, at the beginning of 2006 the Ministry of Health indicated the measures to be taken in the national preparedness and response to a pandemic flu, and the national Legislative Decree 25 January 2010, n. 9 makes implementing the EU Directive 2005/94/CE on Community measures to combat avian flu. Moreover, an article published in June 2010 show a new route of transmission of avian viruses by birds. The topic on avian flu, especially aimed at the protection of workers potentially exposed, has been long the subject of studies, and in particular for operators belonging to the Corpo Nazionale dei Vigili del Fuoco (C.N.VV.F.). In particular, in the context of the measures taken to address any outbreak of avian flu, were carried out one manual addressed to operators by C.N.VV.F. and to so-called managers/operators of the emergency public service workers represented by the operators of the C.N.VVF. and of Police, Civil Protection, and Voluntary Organisations of rescue enclosed in Civil Protection Service. It is necessary to reiterate the importance of continued and growing of the preparation and information for workers, brought to the operators themselves useful about the adoption of preventive and protective measures by the workers belonging to groups at risk of potential exposure to avian influenza viruses.


Molecular mechanics of filamin's rod domain.
Rearrangement of the actin cytoskeleton is integral to cell shape and function. Actin-binding proteins, e.g., filamin, can naturally contribute to the mechanics and function of the actin cytoskeleton. The molecular mechanical bases for filamin's function in actin cytoskeletal reorganization are examined here using molecular dynamics simulations. Simulations are performed by applying forces ranging from 25 pN to 125 pN for 2.5 ns to the rod domain of filamin. Applying small loads ( approximately 25 pN) to filamin's rod domain supplies sufficient energy to alter the conformation of the N-terminal regions of the rod. These forces break local hydrogen bond coordination often enough to allow side chains to find new coordination partners, in turn leading to drastic changes in the conformation of filamin, for example, increasing the hydrophobic character of the N-terminal rod region and, alternatively, activating the C-terminal region to become increasingly stiff. These changes in conformation can lead to changes in the affinity of filamin for its binding partners. Therefore, filamin can function to transduce mechanical signals as well as preserve topology of the actin cytoskeleton throughout the rod domain.