A non-antibacterial chemically-modified tetracycline inhibits mammalian collagenase activity.
Tetracyclines (including the semi-synthetic analogues, minocycline and doxycycline) are considered useful adjuncts in periodontal therapy because they suppress Gram-negative periodontopathogens. Recently, these antibiotics were found to inhibit mammalian collagenase activity, a property which may also be of therapeutic value. It has been suggested that the anti-collagenase properties of the tetracyclines are independent of their antibiotic efficacy. To advance this hypothesis further, we chemically converted tetracycline hydrochloride to its non-antimicrobial analogue, de-dimethylaminotetracycline. This chemically-modified tetracycline (CMT), although no longer an effective antibiotic, was found to inhibit the in vitro activity of collagenase from partially purified extracts of human rheumatoid synovial tissue and rachitic rat epiphysis. In a preliminary in vivo study, pathologically-excessive collagenase in skin and gingiva was induced by rendering adult male rats diabetic, and the oral administration of CMT to these rats significantly reduced the excessive collagenase activity in both tissues. Moreover, CMT administration did not affect the severe hyperglycemia in these rats but did prevent, at least in part, the diabetes-induced loss of body weight, skin weight, and skin collagen mass; these effects suggest a lack of toxicity in this animal model. A proposed clinical advantage of CMT over conventional tetracyclines, in the treatment of diseases characterized by excessive collagenolytic activity, is the lack of development of antibiotic-resistant micro-organisms during prolonged use. However, the consideration of clinical trials to support this hypothesis must await further laboratory and extensive toxicity tests.


Lipid Lowering Effect of Punica granatum L. Peel in High Lipid Diet Fed Male Rats.
Many herbal medicines have been recommended for the treatment of dyslipidemia. The antilipidemic effect of hydroethanolic extract of pomegranate peel (Punica granatum L.) was investigated in high lipid diet fed male rats. Intraperitoneally administration of pomegranate peel extract (50, 100, 200, and 300 mg/kg body weight) for 23 days on the levels of serum cholesterol, triglycerides, LDL, HDL, alkaline phosphatase (AP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in high lipid diet fed male rats was evaluated. Treatment of pomegranate extract decreased body weight in treated rats, significantly. Administration of the plant extract significantly decreased serum total cholesterol, triglycerides, LDL-C, alkaline phosphatise, AST, and ALT levels, whereas it increased serum HDL-C in high lipid diet fed rats in comparison to saline control group. Also, histopathological study showed that treatment of pomegranate peel extract attenuates liver damage in high lipid diet fed rats in comparison to saline group. It is concluded that the plant should be considered as an excellent candidate for future studies on dyslipidemia.


Patterns of mycobacterium avium culture and PCR positivity in immunodeficient HIV-infected patients: progression from localized to systematic disease, German Aids Study Group (GASG/IDKF).
Our aim was to establish the frequency and the longitudinal pattern of MAC culture positivity in late stage HIV-infected patients. Two other aims were to analyse risk factors for progression from localized to systemic disease and the value of PCR diagnosis using blood specimens. A total of 107 patients were recruited to be followed for 32 weeks. Prior MAC treatment and CD4 > 100/microliters were exclusion criteria. A total of 56 patients showed M. avium in at least 1 culture. 10/37 patients with MAC detected by culture first in 'non-sterile' specimens (stool, sputum) and urine progressed to systemic disease as determined by positive blood culture. Risk factors associated with this progression were a high symptom score at baseline, lymphadenopathy, anaemia, and low platelets. PCR was less sensitive than culture in detection of M. avium in blood specimens: Only 7/29 patients with positive blood cultures had a positive PCR at the same time. We conclude that symptomatic patients with advanced HIV-infection have a high frequency of MAC detection. Progression from localized to systemic culture positivity is associated with risk factors. Early 'pre-emptive' therapy is discussed.


Bulk binary ZrO2-based oxides as highly active alternative-type catalysts for non-oxidative isobutane dehydrogenation.
Bulk binary ZrO2-based oxides efficiently catalyse non-oxidative dehydrogenation of isobutane to isobutylene. Their activity strongly depends on the kind of second metal oxide. So designed CrZrOx showed superior activity to industrially relevant catalysts with supported Pt or CrOx species. It was also stable under alternating dehydrogenation and oxidative regeneration cycles over ca. 110 h under different reaction conditions between 550 and 600 °C.


Comparison between Intracoronary Abciximab and Intravenous Eptifibatide Administration during Primary Percutaneous Coronary Intervention of Acute ST-Segment Elevation Myocardial Infarction.
Administration of glycoprotein IIb/IIIa inhibitors is an effective adjunctive treatment strategy during primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI). Recent data suggest that an intracoronary administration of these drugs can increase the efficacy of PPCI. This study was done to find any potential difference in terms of efficacy of administering intracoronary Abciximab vs. intravenous Eptifibatide in primary PPCI. A total of 40 STEMI patients who underwent PPCI within 12 hours of symptom onset were randomized to either an intracoronary Abciximab (0.25 μg/kg) bolus or two boluses of intravenous Eptifibatide (0.180 μg/kg) each 10 minutes. The primary end points were enzymatic infarct size, myocardial reperfusion measured as ST-segment resolution (STR), and post-procedural thrombolysis in myocardial infarction (TIMI) grade flow of the infarct-related artery. The secondary end points were intra-procedural adverse effect (arrhythmia) and no-reflow phenomenon, in-hospital mortality, reinfarction, hemorrhage, and post-procedural global systolic function. Post-procedural TIMI grade 3 flow was achieved in 95% and 90% of the intracoronary Abciximab and intravenous Eptifibatide groups, respectively (p value = 0.61). The infarct size, as assessed by the area under the curve of creatine phosphokinase-MB in the first 48 hours after PPCI (μmol/L/hr), was similar between the intracoronary Abciximab and intravenous Eptifibatide groups: 6591 (interquartile range [IQR], 3006.0 to 11112.0) versus 7,294 (IQR, 3795.5 to 11803.5); p value = 0.59. Complete STR was achieved in 55% and 45% of the intracoronary Abciximab and intravenous Eptifibatide groups, respectively (p value = 0.87). No deaths, urgent revascularizations, reinfarctions, or TIMI major bleeding events were observed in either group. The intracoronary administration of Abciximab was not superior to the intravenous administration of Eptifibatide in the STEMI patients who underwent primary PCI.


Relation between CIDNP formed upon geminate and bulk recombination of radical pairs.
A theoretical approach to time-resolved Chemically Induced Dynamic Nuclear Polarization (CIDNP) is proposed, which allows one to obtain the general relation between polarization formed upon recombination of geminate spin-correlated radical pairs, the so-called G-pairs, and upon recombination of radical pairs formed by encounters of free radicals in solution, the so-called F-pairs. This relation is described by a universal parameter denoted as γ. In this work, the γ value is computed for the arbitrary spin multiplicity, singlet or triplet, of the precursor of the G-pairs as well as for arbitrary recombination rate constants of radical pairs in singlet and triplet states, kS and kT, respectively. Furthermore, the treatment is extended to the situation where radicals undergo transformation resulting in different reactivity or magnetic parameters for F-pairs and G-pairs. The proposed theory enables modeling of time-resolved CIDNP data in cases where (i) both recombination channels are active and (ii) fast protonation/deprotonation of radicals changes the effective γ value.


Determination of active substances in antiallergic and antiphlogistic multicomponent preparations by high performance liquid chromatography (HPLC).
The aim of the present study was the elaboration of an HPLC method enabling the identification and determination of the content of selected compounds occurring in multicomponent preparations applied in allergic and non-allergic diseases of upper respiratory tracts. These compounds include: buzepide methyl iodide, clocinizine dihydrochloride, phenylpropanolamine hydrochloride, pseudoephedrine sulfate and dexbrompheniramine maleate. The elaborated HPLC method shows that a good separation of the mentioned compounds is feasible. The regression analysis has demonstrated linearity of the method in concentration range suitable for the intended experiments. The determination of the compounds in pharmaceutical preparations and the statistical evaluation of the results indicate that both the selectivity and precision of the method are good.


Characteristics of transcranial Doppler signal enhancement using a phospholipid-containing echocontrast agent.
Ultrasound attenuation caused by the skull is a major limitation of transcranial Doppler. Echocontrast agents (EAs) may solve this problem. The aim of the present study was to investigate the characteristics of a new echocontrast agent (BY963) containing air bubbles stabilized by phospholipids. Nine healthy volunteers received three different doses (2.5, 5.0, and 10 mL) of BY963 at an injection rate of 0.25 mL/s. The Doppler signal amplitude obtained from the middle cerebral artery was recorded with a 2-MHz pulsed-wave Doppler system. After complete decay of the signal enhancement, upward stroking of the veins of the upper arm was performed to evaluate the stability of the EA in the venous system. A dose-dependent increase of at least 30 dB in the Doppler signal amplitude lasted 19 to 47, 35 to 64, and 48 to 126 heart cycles (68% range) after 2.5, 5.0, and 10 mL EA, respectively. In 6 cases, there was a biphasic increase in EA enhancement. Upward stroking of the forearm, in general 12 to 18 minutes after administration, caused a Doppler signal enhancement of at least 30 dB in 6 cases. Each injection of BY963 caused a diagnostically relevant Doppler signal enhancement. A considerable amount of EA remained stable in the venous system for at least 12 minutes. The biphasic dose-response fits to models of dilution-indicator theory and indicates free recirculation, as well as a nonlinear washout curve.


Using bioinformatics and genome analysis for new therapeutic interventions.
The genome era provides two sources of knowledge to investigators whose goal is to discover new cancer therapies: first, information on the 20,000 to 40,000 genes that comprise the human genome, the proteins they encode, and the variation in these genes and proteins in human populations that place individuals at risk or that occur in disease; second, genome-wide analysis of cancer cells and tissues leads to the identification of new drug targets and the design of new therapeutic interventions. Using genome resources requires the storage and analysis of large amounts of diverse information on genetic variation, gene and protein functions, and interactions in regulatory processes and biochemical pathways. Cancer bioinformatics deals with organizing and analyzing the data so that important trends and patterns can be identified. Specific gene and protein targets on which cancer cells depend can be identified. Therapeutic agents directed against these targets can then be developed and evaluated. Finally, molecular and genetic variation within a population may become the basis of individualized treatment.


Global partitioning of NOx sources using satellite observations: relative roles of fossil fuel combustion, biomass burning and soil emissions.
We use space-based observations of NO2 columns from the Global Ozone Monitoring Experiment (GOME) to derive monthly top-down NOx emissions for 2000 via inverse modeling with the GEOS-CHEM chemical transport model. Top-down NOx sources are partitioned among fuel combustion (fossil fuel and biofuel), biomass burning and soils by exploiting the spatio-temporal distribution of remotely sensed fires and a priori information on the location of regions dominated by fuel combustion. The top-down inventory is combined with an a priori inventory to obtain an optimized a posteriori estimate of the relative roles of NOx sources. The resulting a posteriori fuel combustion inventory (25.6 TgN year(-1)) agrees closely with the a priori (25.4 TgN year(-1)), and errors are reduced by a factor of 2, from +/- 80% to +/- 40%. Regionally, the largest differences are found over Japan and South Africa, where a posteriori estimates are 25% larger than a priori. A posteriori fuel combustion emissions are aseasonal, with the exception of East Asia and Europe where winter emissions are 30-40% larger relative to summer emissions, consistent with increased energy use during winter for heating. Global a posteriori biomass burning emissions in 2000 resulted in 5.8 TgN (compared to 5.9 TgN year(-1) in the a priori), with Africa accounting for half of this total. A posteriori biomass burning emissions over Southeast Asia/India are decreased by 46% relative to a priori; but over North equatorial Africa they are increased by 50%. A posteriori estimates of soil emissions (8.9 TgN year(-1)) are 68% larger than a priori (5.3 TgN year(-1)). The a posteriori inventory displays the largest soil emissions over tropical savanna/woodland ecosystems (Africa), as well as over agricultural regions in the western U.S. (Great Plains), southern Europe (Spain, Greece, Turkey), and Asia (North China Plain and North India), consistent with field measurements. Emissions over these regions are highest during summer at mid-latitudes and during the rainy season in the Tropics. We estimate that 2.5-4.5 TgN year(-1) are emitted from N-fertilized soils, at the upper end of previous estimates. Soil and biomass burning emissions account for 22% and 14% of global surface NOx emissions, respectively. We infer a significant role for soil NOx emissions at northern mid-latitudes during summer, where they account for nearly half that of the fuel combustion source, a doubling relative to the a priori. The contribution of soil emissions to background ozone is thus likely to be underestimated by the current generation of chemical transport models.


Bioorthogonal Click Chemistry: An Indispensable Tool to Create Multifaceted Cell Culture Scaffolds.
Over the past decade, bioorthogonal click chemistry has led the field of biomaterial science into a new era of diversity and complexity by its extremely selective, versatile, and biocompatible nature. In this viewpoint, we seek to emphasize recent endeavors of exploiting this versatile chemistry toward the development of poly(ethylene glycol) hydrogels as cell culture scaffolds. In these cell-laden materials, the orthogonality of these reactions has played an effective role in allowing the creation of diverse biochemical patterns in complex biological environments that provide new found opportunities for researchers to delineate and control cellular phenotypes more precisely than ever.


Interrater reliability and agreement between children with visual impairment and their parents on participation and quality of life.
To investigate interrater reliability and agreement between children with visual impairment (VI) and their parents on participation and quality of life and factors associated with disagreement. Children 7-17 years and their parents completed the PAI-CY 7-12 (n = 180) and 13-17 (n = 65), the KIDSCREEN-27 (n = 250) and the CASP (n = 70). Mean scores of children and parents were compared, with effect sizes for the differences. Interrater reliability was evaluated using intraclass correlation coefficients (ICCs), whereas agreement was assessed using the Bland-Altman limits of agreement. Linear regression analyses examined child- and proxy-related factors associated with discrepancies. On average, children rated their participation and quality of life as significantly better than their parents on most (sub)scales, but with wide range of disagreement. Effect sizes were large for the PAI-CY 7-12 (0.86) and 13-17 (0.86) and small for the CASP (0.36) and KIDSCREEN-27 (0.18-0.28). Interrater reliability was poor for the PAI-CY 7-12 (ICC = 0.29) and most KIDSCREEN-27 subscales (ICC =0.18-0.32), moderate for the PAI-CY 13-17 (ICC =0.43) and the KIDSCREEN-27 Physical Wellbeing subscale (ICC = 0.46) and good for the CASP (ICC = 0.63). Comorbidity was significantly associated with greater discrepancies on participation scales. Children with VI and their parents have different perspectives on the child's participation and quality of life. Disagreement was largest on participation scales and smallest on quality of life subscales, while opposite results were found for interrater reliability. Reports of children and parents seem to be complementary and are both relevant to obtain a complete picture of the burden of VI and relevant to inform healthcare decisions.


Economic considerations of breeding for polledness versus disbudding in beef cattle.
The domestication of animals has rendered horns less necessary for survival. Moreover, the use of polled and disbudded animals is interesting in order to avoid injuries of animals and handlers, among other advantages. We therefore conducted a comparative economic analysis of different traditional disbudding techniques versus selective breeding for polledness in Nelore cattle, the main beef breed of tropical systems in Brazil. The cost to obtain animals without horns was estimated in three different scenarios: disbudding with hot iron, disbudding with caustic paste, and phenotypic selection for polled animals. Price quotations of the materials were obtained in different states of the country and averaged. An initial frequency of horned animals of 92.16% was obtained based on the records of the Brazilian Association of Zebu Breeders. Selective breeding was found to be the best cost-effective scenario. This result differs from intensive production systems of dairy cattle in which traditional disbudding continues to be the best cost-effective scenario. The main explanation is the lack of difference in the price of Nelore semen from polled and horned bulls. Phenotypic selection for polled animals is the best cost-effective method, and it is in accordance with welfare practices. Care should be taken regarding the intensive use of few polled breeding animals in order to avoid inbreeding depression in other traits.


TNF alpha-mediated disruption of spermatogenesis in response to Sertoli cell injury in rodents is partially regulated by MMP2.
Mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury in peripubertal rodents results in the stimulation of germ cell apoptosis through an interaction of FAS/FASL between these two cell types. During this peripubertal period, an early spike in the incidence of germ cell apoptosis occurs during the first wave of spermatogenesis and is essential for the development of functional spermatogenesis in adults. Our previous observations revealed that soluble tumor necrosis factor alpha (sTNFA) released by germ cells after MEHP exposure consequently resulted in a robust induction of FASL by Sertoli cells. Metalloproteinases (MPs) are essential for processing the TNFA precursor to its soluble form and its ability to bind to TNFRSF1A. The activity of MPs is regulated by the tissue inhibitors of MPs (TIMPs) family. Herein we report that TIMP2 is predominately expressed in Sertoli cells and that protein levels decrease in a time-dependent manner after MEHP exposure. The secretion of matrix MP 2 (MMP2) in primary rat Sertoli cell-germ cell cocultures is induced after MEHP exposure, and its activity increases in a time-dependent manner. The addition of SB-3CT, a specific gelatinase inhibitor, decreases the activity of MMP2 and significantly reduces MEHP-enhanced sTNFA production in primary cocultures. In vivo challenges with SB-3CT decrease sTNFA and reduce MEHP-induced testicular germ cell apoptosis. In primary cocultures, MEHP exposure causes a 9.46-fold increase in sTNFA, while the addition of recombinant MMP2 protein results in a 5.4-fold increase in sTNFA, suggesting that MEHP-induced MMP2 is in part responsible for the activation of TNFA in the testis. Taken together, these observations indicate the distinct role of specific MPs in response to toxicant-induced Sertoli cell injury, providing further insights into the mechanism by which Sertoli cells control the sensitivity of germ cells to undergo apoptosis.


Development of mouse-bank vole interspecific chimaeric embryos.
One bank vole (Clethrionomys glareolus) embryo and two mouse embryos were combined at the 8- to 16-blastomere stage and cultured in vitro for 33-47 h. In 66% of cases single regular blastocysts were formed. The chimaeric composition of blastocysts was confirmed karyologically. Out of the 222 blastocysts transplanted to 49 pseudopregnant mouse recipients, a total of 52 implantations were found in 20 recipients. Among the 52 implantations, 14 contained embryos and the remaining were resorptions. The majority of embryos were abnormal and fell into two categories: (1) groups of cells surrounded by Reichert's membrane and lying freely in a cavity filled with giant trophoblastic cells, (2) small and retarded egg-cylinders usually composed of endoderm and ectoderm only, and containing a proamniotic cavity. The ectoplacental cone of these embryos was poorly developed or lacking altogether. Two normal-looking embryos were recovered on the 9th and 10th day (4-somite and ca. 12-somite stage). Chimaerism of the younger embryo was confirmed karyologically. No evidence of chimaerism was available in the case of older embryo which was examined histologically. Thirteen implantations examined between 11th and 17th day contained only resorptions. It is suggested that the main cause of the heavy mortality of chimaeric embryos is the profound difference in the course of embryogenesis of these two species immediately following implantation.


Detection of Fake Alcoholic Beverages Using Electrolyte-Free Nanogap Electrochemical Cells.
Because of the similarity of odor, appearance, and chemical structure of methanol and ethanol, measuring the low concentration of methanol in an alcoholic beverage is difficult to perform in a quick, quantitative, and repeatable fashion. However, it is important for people to monitor the content of methanol in a liquor because a high amount of methanol absorbed will result in blindness, coma, and death. In response to this need, we have developed electrolyte-free methanol electrolysis and ethanol electrolysis based on the nanogap electrochemical cells for the methanol and ethanol sensing. Upon applying a voltage, a high electric field across the nanogap cell enhances the solution ionization and the ion transport rate. Moreover, the nanoscale distance between the electrodes provides a shorter path for electrolysis to easily occur. The nanogap electrochemical cells not only make the direct electrolyte-free organic solvent electrolysis possible but also enhance the sensitivity of the chemical of interest in low-concentration solutions without the influence of the added electrolyte. The nanogap electrochemical cells have been demonstrated having high sensitivity to detect 0.15% methanol volume concentration in deionized water solutions without adding any electrolyte, and its ability for the fake alcoholic beverages' detection has successfully demonstrated.


Selectivity at the cleavage/attachment site of phosphatidylinositol-glycan anchored membrane proteins is enzymatically determined.
Nascent precursors of phosphatidylinositol-glycan (PI-G)-linked membrane proteins contain a hydrophobic COOH-terminal sequence of 15-30 residues that is eliminated during processing to yield a newly exposed COOH terminus to which the PI-G moiety is added. There is no consensus as to the primary structure of the terminal peptide but there is a specific requirement for the amino acid destined to become the COOH terminus. In nascent human placental alkaline phosphatase (PLAP), the PI-G tail is attached to Asp-484. Site-directed mutants with glycine, alanine, cysteine, serine, or asparagine (category I) at residue 484 become PI-G tailed, appear in the plasma membrane, and are enzymatically active when expressed in COS cells. Although mutants with glutamic acid, glutamine, proline, tryptophan, leucine, valine, phenylalanine, threonine, methionine, and tyrosine (category II) are expressed equally well, only small amounts appear on the plasma membrane. Furthermore, they are not PI-G tailed and have little alkaline phosphatase activity. Studies with truncated PLAP-489 rule out nonspecific conformational changes in category II mutant proteins as a reason for their failure to be processed in COS cells and point to a specific COOH-terminal processing enzyme. Direct evidence that the selectivity for category I amino acids is enzymatically determined was obtained in a cell-free translation/processing system by using rabbit reticulocyte lysate and CHO cell rough microsomal membranes. In this in vitro system, both category I and category II mutants of PLAP-513 were translated, glycosylated, and cleaved by NH2-terminal signal peptidase. However, an additional and selective cleavage at residue 484 was observed only with category I mutants.


Short- and mid-term effects of covered stent implantation on extremity findings and heart failure in Parkes Weber syndrome: a case report.
Parkes Weber syndrome (PWS) is a congenital disease characterized by vascular malformations, such as arteriovenous fistulas (AVFs). It frequently presents with overgrowth of a lower limb and high-output heart failure. The main treatment is to close vascular malformations. Surgical excision or endovascular coil insertion was performed in a few patients with AVFs. However, vascular covered stent implantation has not been used for treating PWS. A 15-year-old male patient with PWS presented to our hospital because of dyspnoea and massive left upper limb swelling. After initial examination and left upper limb angiography, his symptoms and findings were attributed to the presence of high-flow large AVFs despite the presence of many coils previously inserted. We decided to implant a covered stent along the AVFs between the subclavian and axillary arteries. After stent implantation, the patient's complaints and findings improved during the early term but they relapsed at the 6th month after percutaneous intervention. Here, we report for the first time the use of covered stent implantation and its short and 6 months results in a patient with PWS. Although initial improvements were noted, the clinical outcome at 6 months after stent implantation was poor. This was probably associated with the presence of widespread subtle AVFs or collateral connections among the existing AVFs. Based on our result, we propose that closure of large AVFs is not useful and more definitive interventions, such as limb amputation may be required earlier.


STIM1-directed reorganization of microtubules in activated mast cells.
Activation of mast cells by aggregation of the high-affinity IgE receptors (FcεRI) initiates signaling events leading to the release of inflammatory and allergic mediators stored in cytoplasmic granules. A key role in this process play changes in concentrations of intracellular Ca(2+) controlled by store-operated Ca(2+) entry (SOCE). Although microtubules are also involved in the process leading to degranulation, the molecular mechanisms that control microtubule rearrangement during activation are largely unknown. In this study, we report that activation of bone marrow-derived mast cells (BMMCs) induced by FcεRI aggregation or treatment with pervanadate or thapsigargin results in generation of protrusions containing microtubules (microtubule protrusions). Formation of these protrusions depended on the influx of extracellular Ca(2+). Changes in cytosolic Ca(2+)concentration also affected microtubule plus-end dynamics detected by microtubule plus-end tracking protein EB1. Experiments with knockdown or reexpression of STIM1, the key regulator of SOCE, confirmed the important role of STIM1 in the formation of microtubule protrusions. Although STIM1 in activated cells formed puncta associated with microtubules in protrusions, relocation of STIM1 to a close proximity of cell membrane was independent of growing microtubules. In accordance with the inhibition of Ag-induced Ca(2+) response and decreased formation of microtubule protrusions in BMMCs with reduced STIM1, the cells also exhibited impaired chemotactic response to Ag. We propose that rearrangement of microtubules in activated mast cells depends on STIM1-induced SOCE, and that Ca(2+) plays an important role in the formation of microtubule protrusions in BMMCs.


Application of Quantitative Targeted Absolute Proteomics to Profile Protein Expression Changes of Hepatic Transporters and Metabolizing Enzymes During Cholic Acid-Promoted Liver Regeneration.
Preoperative administration of cholic acid (CA) may be an option to increase the liver volume before elective liver resection surgery, so it is important to understand its effects on liver functionality for drug transport and metabolism. The purpose of this study is to clarify the absolute protein expression dynamics of transporters and metabolizing enzymes in the liver of mice fed with CA-containing diet for 5 days (CA1) and mice fed with CA-containing diet for 5 days followed by diet without CA for 7 days (CA2), in comparison with non-CA-fed control mice. The CA1 group showed the increased liver weight, cell proliferation index, and oxidative stress, but no increase in apoptosis. Quantitative targeted absolute proteomics revealed (1) decreases in basolateral bile acid transporters Na+-taurocholate cotransporting polypeptide, anion transporting polypeptide (oatp) 1a1, and oatp1b2, bile acid synthesis-related enzymes cyp7a1 and cyp8b1, and drug transporters breast cancer resistance protein, multidrug resistance-associated protein 6, ent1, and oatp2b1; and (2) increases in glutathione biosynthetic enzymes and drug-metabolizing enzyme cyp3a11. Liver concentrations of reduced and oxidized glutathione were both increased. In the CA2 group, the increased liver weight was maintained, whereas the biochemical features and protein profiles were restored to the non-CA-fed control levels. These findings suggest that CA administration alters liver functionality per body during liver regeneration and restoration.


[Locomo 25--a screening tool for risk of locomotive syndrome].
Locomo 25 was developed as a screening tool of locomotive syndrome by Japanese orthopedic surgeon group in 2008. It contains 25 questions in terms of musculoskeletal disorder such as walking disability, difficulty in daily living, or suffering pain on body. Its reliability and validity were already confirmed through multi-center study including 731 Japanese elderly people (over 65 y.o. average 77 y.o.). The cutoff score for identifying locomotive syndrome was set at 16, and list-upped person is considered as under high-risk condition who may soon require care services without some medical interventions. We can use Locomo 25 not only as a screening tool of locomotive syndrome but also as a measuring scale for evaluating effects of interventions in individuals.


Mutational Signatures in Breast Cancer: The Problem at the DNA Level.
A breast cancer genome is a record of the historic mutagenic activity that has occurred throughout the development of the tumor. Indeed, every mutation may be informative. Although driver mutations were the main focus of cancer research for a long time, passenger mutational signatures, the imprints of DNA damage and DNA repair processes that have been operative during tumorigenesis, are also biologically illuminating. This review is a chronicle of how the concept of mutational signatures arose and brings the reader up-to-date on this field, particularly in breast cancer. Mutational signatures have now been advanced to include mutational processes that involve rearrangements, and novel cancer biological insights have been gained through studying these in great detail. Furthermore, there are efforts to take this field into the clinical sphere. If validated, mutational signatures could thus form an additional weapon in the arsenal of cancer precision diagnostics and therapeutic stratification in the modern war against cancer. Clin Cancer Res; 23(11); 2617-29. ©2017 AACRSee all articles in this CCR Focus section, "Breast Cancer Research: From Base Pairs to Populations."


[Does interventional radiological treatment (transcatheter arterial chemoembolization/transarterial infusion) improve the prognosis of patients with unresectable and recurrent hepatocellular carcinomas?].
We report herein the usefulness of interventional radiological treatment( IVR) for hepatocellular carcinomas( HCCs), based on the results of transcatheter arterial chemoembolization( TACE) and transarterial infusion( TAI). The study included 256 cases of HCC. TACE and TAI were performed for durations permitted by the degree of liver damage. Results(: 1) TACE was performed in 224 cases( average: 4.5 times, range: 1-14 times), and TAI was performed in 32 cases( average: 2.3 times, range: 1-8 times).( 2) The 3- and 5-year survival rates for all cases were 45.5% and 31.6%, respectively.( 3) We classified all cases according to the number of HCCs, solitary, 2-4, and multiple HCCs, and found no significant differences in the survival rate between the 3 groups( p=0.207),( 4) TAI was followed by TACE in non-responsive cases, and the median survival time of the TAI group was 8.5 months. We can expect benefits from repeated TACE treatment in the multiple HCCs group, compared to the solitary HCC group. TAI followed by TACE might improve the prognosis of unresectable and recurrent HCCs. Therefore, we conclude that IVR has clinical benefit as local treatment for HCC.


Physiological Changes to the Cardiovascular System at High Altitude and Its Effects on Cardiovascular Disease.
Riley, Callum James, and Matthew Gavin. Physiological changes to the cardiovascular system at high altitude and its effects on cardiovascular disease. High Alt Med Biol. 18:102-113, 2017.-The physiological changes to the cardiovascular system in response to the high altitude environment are well understood. More recently, we have begun to understand how these changes may affect and cause detriment to cardiovascular disease. In addition to this, the increasing availability of altitude simulation has dramatically improved our understanding of the physiology of high altitude. This has allowed further study on the effect of altitude in those with cardiovascular disease in a safe and controlled environment as well as in healthy individuals. Using a thorough PubMed search, this review aims to integrate recent advances in cardiovascular physiology at altitude with previous understanding, as well as its potential implications on cardiovascular disease. Altogether, it was found that the changes at altitude to cardiovascular physiology are profound enough to have a noteworthy effect on many forms of cardiovascular disease. While often asymptomatic, there is some risk in high altitude exposure for individuals with certain cardiovascular diseases. Although controlled research in patients with cardiovascular disease was largely lacking, meaning firm conclusions cannot be drawn, these risks should be a consideration to both the individual and their physician.


Damage Quantification with Embedded Piezoelectric Aggregates Based on Wavelet Packet Energy Analysis.
Cement-based components have been widely used in civil engineering structures. However, due to wearing and deterioration, the cement-based components may have brittle failure. To provide early warning and to support predictive reinforcement, the piezoelectric materials are embedded into the cement-based components to excite and receive elastic waves. By recognizing the abnormalities in the elastic waves, hidden damage can be identified in advance. However, few research has been published regarding the damage quantification. In this paper, the wavelet packet analysis is adopted to calculate the energy of the transmitted elastic waves based on the improved piezoelectric aggregates (IPAs). Due to the growth of the damage, less elastic waves can pass through the damage zone, decreasing the energy of the acquired signals. A set of cement beams with different crack depths at the mid-span is tested in both numerical and experimental ways. A damage quantification index, namely the wavelet packet-based energy index (WPEI), is developed. Both the numerical and experimental results demonstrate that the WPEI decreases with respect to the crack depth. Based on the regression analysis, a strong linear relationship has been observed between the WPEI and the crack depth. By referring to the linear relationship, the crack depth can be estimated by the WPEI with a good accuracy. The results demonstrated that the use of the IPAs and the WPEI can fulfill the real-time quantification of the crack depth in the cement beams.


Use of JAR-Based Analysis for Improvement of Product Acceptance: A Case Study on Flavored Kefirs.
A common question of dairy product developments is the possible success of the new product. Several publications reported successful results using just-about-right (JAR) scales; although there is some debate about their advantages/disadvantages. This study highlights the limitations and opportunities of JAR scales and penalty analysis of fruit flavored kefirs. The first question is whether penalty analysis results help to improve the product and thus its overall liking (OAL)? The second question is what happens to those who rated the products "ideal" (JAR) before product development when evaluating the new products? Fruit flavored live-flora stirred-type kefir samples were formulated and evaluated by 92 consumers before and after the JAR-based product development. The OAL of two products significantly increased after product development. A new visualization tool is introduced, which shows what happens to those who rated the attribute as JAR but the attribute has been modified. A general product development scheme is also introduced for JAR-based kefir product development.


Estrogen and luminal stimulation of rat uterine kallikrein.
To understand the regulation of rat uterine kallikrein, we evaluated its variations in animals that had been ovariectomized and supplemented with estradiol or progesterone, in pseudopregnant animals intraluminally oil-stimulated or unstimulated, and in unilaterally pregnant animals. The content of kallikrein, determined by an RIA highly specific for rK1 (true tissue kallikrein), rose in ovariectomized rats with estradiol supplementation (0.28 +/- 0.03 to 0.44 +/- 0.05 ng/mg) and decreased with progesterone (0.13 +/- 0.02 ng/mg; n = 15; p < 0.001). Kallikrein content rose from Day 1 of pseudopregnancy (PP1) to a maximum on PP7 (0.18 +/- 0.01 to 0.39 +/- 0.04 ng/mg protein; n = 36; p < 0.001). On PP7 with unilateral oil intraluminal stimulation, the decidualized horn had higher kallikrein content than did the contralateral (0.98 +/- 0.09 vs. 0.35 +/- 0.05 ng/mg protein; n = 7; p < 0.001). Immunocytochemistry revealed that mainly rK1 is localized in the luminal and glandular epithelium, and it increased in the stimulated horn. In the unilaterally pregnant rat on Day 7, the fertile horn had a higher kallikrein content than its contralateral control (0.71 +/- 0.07 vs. 0.37 +/- 0.03 ng/mg protein, p < 0.001; n = 8), as well as a higher kininogenase activity (239 +/- 34.3 vs. 83.5 +/- 7.9 ng bradykinin(BK)/h per horn, p < 0.003; and 945 +/- 90 vs. 585 +/- 40 ng BK/h per gram tissue, p < 0.002; n = 6). These results indicate that estrogen stimulates, whereas progesterone inhibits, kallikrein production, and that hormonal regulation is overridden by intraluminal stimulation, thus associating the enzyme with decidualization.


Hierarchical CdS Nanowires Based Rigid and Flexible Photodetectors with Ultrahigh Sensitivity.
Hierarchical CdS nanowires were synthesized via a facile vapor transport method, which were used to fabricate both rigid and flexible visible-light photodetectors. Studies found that the rigid photodetectors on SiO2/Si substrate showed ultrahigh photo-dark current ratio up to 1.96 × 10(4), several orders of magnitude higher than previously reported CdS nanostructures, as well as high specific detectivity (4.27 × 10(12) Jones), fast response speed and excellent environmental stability. Highly flexible photodetectors were also fabricated on polyimide substrate, which exhibited comparable photoresponse performance as the rigid one. In addition, the as-prepared flexible devices displayed excellent mechanical flexibility, electrical stability and folding endurance. The results indicate that the hierarchical CdS nanowires may be good candidates for nanoscale optoelectronic devices such as high-efficiency photoswitches and highly photosensitive detectors.


[Psychology and psychiatry in the 7th Navy Hospital in the light of its 75th anniversary].
2007 is a year of 75 years' jubilee of VII Navy Hospital in Gdańsk. Reminding of it's history seems to be important element of military psychologists and psychiatrists conference organized by hospital's personnel. SHORT HISTORY OF THE VII NAVY HOSPITAL IN GDANSK: The VII Navy Hospital came into existence in 1st May of 1932 in Gdynia Oksywie and included one hundred beds on surgery and general practice wards. In 1949 the hospital has been connected with general military hospital in Gdańsk and has got it's actual place. There have been fifteen commandants since that time. Commandore Piotr Drabarek is actual commandant of this hospital. The most interesting person in a group of commandants was admiral Wiesław Lasiński, later chancellor of Military Medical Academy in Lódź. NOWADAYS OF THE VII NAVY HOSPITAL: The hospital actually includes twelve wards. There works one professors, fifteen physicians with degree of doctor and few doctors with open doctoral dissertations. Modern equipment, highly qualified medical staff, ensure professional medical care. History of the psychology and psychiatry The VII Navy Hospital in Gdańsk hadn't included psychiatry ward until seventieth years of XX century. Psychosomatic ward came to existence in 1970 and in 1975 has become psychiatry. Actual boss of the ward is doctor Alicja Furmańska. It is worth to say something about psychosomatic ward which came to existence in 2005 and is lead by Ltd. Małgorzata Zychlińska. It is professional medical base in Polish army. Four hundred patients is treated in this ward in a year on forty beds. In addition, both wards employs five doctors and five psychologists. They control 3500 patients a year. HISTORY REFLECTION: In spite of many historical, political, economical event difficulties the institution which bases on determinations, competence and personal attitude develops constantly. Psychiatry and psychology ward in the VII Navy Hospital in Gdańsk are said "unsinkable".


Neonatal Morbidity Count Is Associated With a Reduced Likelihood of Achieving Recommendations for Protein, Lipid, and Energy in Very Low Birth Weight Infants: A Prospective Cohort Study.
Serious morbidity may elevate nutrient requirements and affect adherence to feeding guidelines for very low birth weight (VLBW) infants. An understanding of factors affecting nutrient intakes of VLBW infants will facilitate development of strategies to improve nutrient provision. Our aim was to examine the impact of neonatal morbidity count on achieving recommended nutrient intakes in VLBW infants. VLBW infants enrolled in the Donor Milk for Improved Neurodevelopmental Outcomes trial (ISRCTN35317141, n = 363) were included. Serious morbidities and daily parenteral and enteral intakes were collected prospectively. Median intakes of infants with and without ≥1 morbidity met protein recommendations (3.5-4.5 g/kg/d) by week 2, although not maintained after week 4. Infants with ≥1 morbidity (vs without) were 2 weeks slower in achieving lipid (4.8-6.6 g/kg/d; week 4 vs 2) and energy (110-130 kcal/kg/d; week 5 vs 3) and 1 week slower in achieving carbohydrate recommendations (11.6-13.2 g/kg/d; week 4 vs 3). Adjusted hazard ratios of first achieving recommendations on any given day in infants with any 1 or 2 morbidities were 0.6 (95% confidence interval [CI], 0.5-0.9) and 0.6 (0.4-0.9), respectively, for protein; 0.5 (0.4-0.7) and 0.3 (0.2-0.5) for lipid; and 0.5 (0.4-0.7) and 0.3 (0.2-0.4) for energy. Morbidity is associated with a decreased likelihood of achieving lipid and consequently energy recommendations. This and the decline in protein intakes after the early neonatal period require further investigation to ensure optimal nutrition in this vulnerable population.


Driving and diabetes: problems, licensing restrictions and recommendations for safe driving.
Driving is a complex process that places considerable demands on cognitive and physical functions. Many complications of diabetes can potentially impair driving performance, including those affecting vision, cognition and peripheral neural function. Hypoglycemia is a common side-effect of insulin and sulfonylurea therapy, impairing many cognitive domains necessary for safe driving performance. Driving simulator studies have demonstrated how driving performance deteriorates during hypoglycemia. Driving behavior that may predispose to hypoglycemia while driving is examined. Studies examining the risk of road traffic accidents in people with insulin-treated diabetes have produced conflicting results, but the potential risk of hypoglycemia-related road traffic accidents has led to many countries imposing restrictions on the type and duration of driving licenses that can be issued to drivers with diabetes. Guidance that promotes safe driving practice has been provided for drivers with insulin-treated diabetes, which is the group principally addressed in this review.


Metastatic melanoma: scientific rationale for sorafenib treatment and clinical results.
In advanced metastatic melanoma (AJCC stage IV), the prognosis is still poor, and views differ on the appropriate systemic treatment for these patients. Therefore, new approaches in therapeutic regimens are mandatory. Sorafenib is an oral multikinase inhibitor that targets 2 classes of kinases which are known to be involved in both tumor proliferation and angiogenesis. These kinases include Raf kinases and the vascular endothelial growth factor (VEGF) receptor. Sorafenib has been evaluated as a single therapy agent as well as in combination with various chemotherapeutical drugs in a number of clinical trials. The vast majority of clinical data exists for patients with advanced renal cell cancer for which sorafenib has been approved by the FDA and EMEA. Very recently, sorafenib was approved for advanced hepatocellular cancers due to its overall survival improvement. Since B-raf gene mutations have been found in 69% of melanoma cell lines, sorafenib was brought into various phase I/II and phase III trials in metastatic melanoma. However, as a single-agent therapy, sorafenib seems to be of limited use. Also, the combination of sorafenib with the chemotherapeutic agents carboplatin and paclitaxel has failed to show superiority in progression-free and overall survival compared to the same chemoregimen plus an oral placebo in a phase III trial (PRISM study). More promising data were observed in large-sized phase II studies on dacarbazine (DTIC) plus sorafenib and temozolomide plus sorafenib. However, these data need to be confirmed in prospective randomized phase III trials. Till then, sorafenib remains an interesting but still experimental new agent for melanoma.


The G-Axis: a growth vector for the mandible.
On the basis of the G-point, defined as the center of the largest circle that is tangent to the internal inferior, anterior, and lingual surfaces of the mandibular symphysis in the sagittal view, a growth axis and its direction are described for each gender from age six to 19.25 years. Incremental growth along the G-Axis, defined by Sella-G-point, is described by regression formulas with correlation coefficients of 0.673 for female subjects and 0.749 for male subjects. The vector (direction) of the growth axis, defined by the angle alpha ((G-Axis)-(S-N)) does not materially alter in the age range studied. At age six in female subjects the angle alpha is 67.16 degrees +/- 3.03 degrees and at age 19.25 it is 66.87 degrees +/- 3.03 degrees, whereas in male subjects it is 66.12 degrees +/- 4.00 degrees and 67.93 degrees +/- 4.00 degrees, respectively. These changes and gender differences are not clinically significant. The data is based on 444 serial lateral cephalograms of 24 female subjects and 24 male subjects. The G-Axis incremental growth change and its vector offer an improved means of quantifying complex mandibular growth in the sagittal plane by using cephalometric measurements relative to and correlated with other craniofacial structures.


Bioconjugation with Maleimides: A Useful Tool for Chemical Biology.
Maleimide chemistry stands out in the bioconjugation toolbox by virtue of its synthetic accessibility, excellent reactivity, and practicability. The second-generation of clinically approved antibody-drug conjugates (ADC) and much of the current ADC pipeline in clinical trials contain the maleimide linkage. However, thiosuccinimide linkages are now known to be less robust than once thought, and ergo, are correlated with suboptimal pharmacodynamics, pharmacokinetics, and safety profiles in some ADC constructs. Rational design of novel generations of maleimides and maleimide-type reagents have been reported to address the shortcomings of classical maleimides, allowing for the formation of robust bioconjugate linkages. This review highlights the main strategies for rational reagent design that have allowed irreversible bioconjugations in cysteines, reversible labelling strategies and disulfide re-bridging.


Recovery of brain dopamine metabolism by branched-chain amino acids in rats with acute hepatic failure.
A decrease in the serum ratio of branched-chain amino acids (BCAAs) to aromatic amino acids (Fischer ratio) reflects the severity of hepatic encephalopathy, and clinical improvement by dietary augmentation with BCAAs has been demonstrated. As behavioral alteration results from changes in central neurotransmission, we investigated the role of BCAA administration on changes in the levels of central neurotransmitters in acute liver injury. Male Wistar rats were subjected to liver ischemia by occluding the left portal vein and hepatic artery for 90 minutes. A 4% BCAA solution containing valine, leucine, and isoleucine was intraperitoneally administered 3 times (8 mL/kg, each) at 1 hour, 6 hours, and 24 hours after vascular reperfusion, and changes in the extracellular concentrations of neurotransmitter amino acids, monoamines, and their metabolites were evaluated in the striatum by a microdialysis procedure. Although the extracellular concentration of dopamine was affected by neither liver ischemia nor BCAA injections, the level of 3,4-dihydroxyphenylacetic acid, a metabolite of dopamine, decreased to 34% in the ischemic group 24 hours after reperfusion. The 3,4-dihydroxyphenylacetic acid level was normalized by treatments with BCAAs. The improvement of deranged cerebral dopaminergic activity may be a contributing factor in the improvement of hepatic encephalopathy by BCAAs.


Staurosporine suppresses survival of HepG2 cancer cells through Omi/HtrA2-mediated inhibition of PI3K/Akt signaling pathway.
Staurosporine, which is an inhibitor of a broad spectrum of protein kinases, has shown cytotoxicity on several human cancer cells. However, the underlying mechanism is not well understood. In this study, we examined whether and how this compound has an inhibitory action on phosphatidylinositol 3-kinase (PI3K)/Akt pathway in vitro using HepG2 human hepatocellular carcinoma cell line. Cell viability and apoptosis were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay, respectively. Glutathione S-transferase (GST) pull-down assay and co-immunoprecipitation were performed to detect protein-protein interactions. Small interfering RNA (siRNA) was used to silence the expression of targeted protein. We found that staurosporine significantly decreased cell viability and increased cell apoptosis in a concentration- and time-dependent manner in HepG2 cancer cells, along with the decreased expressions of PDK1 protein and Akt phosphorylation. Staurosporine was also found to enhance Omi/HtrA2 release from mitochondria. Furthermore, Omi/HtrA2 directly bound to PDK1. Pharmacological and genetic inhibition of Omi/HtrA2 restored protein levels of PDK1 and protected HepG2 cancer cells from staurosporine-induced cell death. In addition, staurosporine was found to activate autophagy. However, inhibition of autophagy exacerbated cell death under concomitant treatment with staurosporine. Taken together, our results indicate that staurosporine induced cytotoxicity response by inhibiting PI3K/Akt signaling pathway through Omi/HtrA2-mediated PDK1 degradation, and the process provides a novel mechanism by which staurosporine produces its therapeutic effects.


The Modified Spare Piriformis and Internus, Repair Externus Approach for Hip Arthroplasty.
We present the case of an 80-year-old Malaysian gentleman who sustained a displaced intracapsular neck of femur (NOF) fracture and underwent a modified SPAIRE (Sparing Piriformis and Internus, Repair Externus) approach for total hip replacement (THR). The standard approach used in our hospital for THR in NOF fractures is the modified Hardinge approach to the hip. We used this modified SPAIRE approach as this patient lives in a 'Mahjong' center and always sits cross-legged on the floor. Therefore, he is at increased risk of an anterior dislocation. This approach is a modification of the standard SPAIRE approach popularized by the Exeter Hip Unit, United Kingdom. In this report, we describe the modification of the SPAIRE approach that has not been described before and the outcome for this patient.


Lifetime prevalence of psychotic and bipolar I disorders in a general population.
Recent general population surveys of psychotic disorders have found low lifetime prevalences. However, this may be owing to methodological problems. Few studies have reported the prevalences of all specific psychotic disorders. To provide reliable estimates of the lifetime prevalences of specific psychotic disorders. General population survey. A nationally representative sample of 8028 persons 30 years or older was screened for psychotic and bipolar I disorders using the Composite International Diagnostic Interview, self-reported diagnoses, medical examination, and national registers. Those selected by the screens were then re-interviewed with the Structured Clinical Interview for DSM-IV. Best-estimate DSM-IV diagnoses were formed by combining the interview and case note data. Register diagnoses were used to estimate the effect of the nonresponders. Diagnosis of any psychotic or bipolar I disorder according to the DSM-IV criteria. The lifetime prevalence of all psychotic disorders was 3.06% and rose to 3.48% when register diagnoses of the nonresponder group were included. Lifetime prevalences were as follows: 0.87% for schizophrenia, 0.32% for schizoaffective disorder, 0.07% for schizophreniform disorder, 0.18% for delusional disorder, 0.24% for bipolar I disorder, 0.35% for major depressive disorder with psychotic features, 0.42% for substance-induced psychotic disorders, and 0.21% for psychotic disorders due to a general medical condition. The National Hospital Discharge Register was the most reliable of the screens (kappa = 0.80). Case notes supplementing the interviews were essential for specific diagnoses of psychotic disorders. Multiple sources of information are essential for accurate estimation of lifetime prevalences of psychotic disorders. The use of comprehensive methods reveals that their lifetime prevalence exceeds 3%.


Assessment and kinetics of soil phosphatase in Brazilian Savanna systems.
The activity and kinetics of soil phosphatases are important indicators to evaluate soil quality in specific sites such as the Cerrado (Brazilian Savanna). This study aimed to determine the activity and kinetic parameters of soil phosphatase in Cerrado systems. Soil phosphatase activity was assessed in samples of native Cerrado (NC), no-tillage (NT), conventional tillage (CT) and pasture with Brachiaria brizantha (PBb) and evaluated with acetate buffer (AB), tris-HCl buffer (TB), modified universal buffer (MUB) and low MUB. The Michaelis-Menten equation and Eadie-Hofstee model were applied to obtain the kinetic parameters of soil phosphatase using different concentrations of p-nitrophenol phosphate (p-NPP). MUB showed the lowest soil phosphatase activity in all soils whereas AB in NC and NT presented the highest. Low MUB decreased interferences in the assessment of soil phosphatase activity when compared to MUB, suggesting that organic acids interfere on the soil phosphatase activity. In NC and NT, soil phosphatase activity performed with TB was similar to AB and low MUB. Km values from the Michaels-Menten equation were higher in NC than in NT, which indicate a lower affinity of phosphatase activity for the substrate in NC. Vmax values were also higher in NC than in NT. The Eadie-Hofstee model suggests that NC had more phosphatase isoforms than NT. The study showed that buffer type is of fundamental importance when assessing soil phosphatase activity in Cerrado soils.


Positive youth development as a guiding framework in sport research: Is it time to plan for a transition?
Positive youth development is a popular guiding framework for studying the psychosocial development of youth. In sport research, for more than two decades, this framework has enhanced our understanding of the mechanisms involved in successful shifts from youth to adulthood. Nonetheless, scholars have recently taken a more critical stance on the positive youth development framework by elucidating some of its shortcomings. To help determine whether it may be warranted to plan for a transition from the positive youth development framework in sport research, a critical commentary is offered. The purpose of this commentary lies in situating three ontologically distinct arguments that depict the shortcomings of the positive youth development framework, namely the operationalization argument, the social justice argument, and the posthumanist argument. This paper is offered as an open invitation to instigate dialogue on what may come next for youth development in sport research and whether planning for a transition is warranted.


Altered Erythropoiesis in Mouse Models of Type 3 Hemochromatosis.
Type 3 haemochromatosis (HFE3) is a rare genetic iron overload disease which ultimately lead to compromised organs functioning. HFE3 is caused by mutations in transferrin receptor 2 (TFR2) gene that codes for two main isoforms (Tfr2α and Tfr2β). Tfr2α is one of the hepatic regulators of iron inhibitor hepcidin. Tfr2β is an intracellular isoform of the protein involved in the regulation of iron levels in reticuloendothelial cells. It has been recently demonstrated that Tfr2 is also involved in erythropoiesis. This study aims to further investigate Tfr2 erythropoietic role by evaluating the erythropoiesis of two Tfr2 murine models wherein either one or both of Tfr2 isoforms have been selectively silenced (Tfr2 KI and Tfr2 KO). The evaluations were performed in bone marrow and spleen, in 14 days' and 10 weeks' old mice, to assess erythropoiesis in young versus adult animals. The lack of Tfr2α leads to macrocytosis with low reticulocyte number and increased hemoglobin values, together with an anticipation of adult BM erythropoiesis and an increased splenic erythropoiesis. On the other hand, lack of Tfr2β (Tfr2 KI mice) causes an increased and immature splenic erythropoiesis. Taken together, these data confirm the role of Tfr2α in modulation of erythropoiesis and of Tfr2β in favoring iron availability for erythropoiesis.


Discovery of two β-1,2-mannoside phosphorylases showing different chain-length specificities from Thermoanaerobacter sp. X-514.
We characterized Teth514_1788 and Teth514_1789, belonging to glycoside hydrolase family 130, from Thermoanaerobacter sp. X-514. These two enzymes catalyzed the synthesis of 1,2-β-oligomannan using β-1,2-mannobiose and d-mannose as the optimal acceptors, respectively, in the presence of the donor α-d-mannose 1-phosphate. Kinetic analysis of the phosphorolytic reaction toward 1,2-β-oligomannan revealed that these enzymes followed a typical sequential Bi Bi mechanism. The kinetic parameters of the phosphorolysis of 1,2-β-oligomannan indicate that Teth514_1788 and Teth514_1789 prefer 1,2-β-oligomannans containing a DP ≥3 and β-1,2-Man2, respectively. These results indicate that the two enzymes are novel inverting phosphorylases that exhibit distinct chain-length specificities toward 1,2-β-oligomannan. Here, we propose 1,2-β-oligomannan:phosphate α-d-mannosyltransferase as the systematic name and 1,2-β-oligomannan phosphorylase as the short name for Teth514_1788 and β-1,2-mannobiose:phosphate α-d-mannosyltransferase as the systematic name and β-1,2-mannobiose phosphorylase as the short name for Teth514_1789.


[Questionnaire survey on the change of asthmatic response, adverse events and product usability due to drug switching between name-brand and generic tulobuterol tapes].
Aggravation of asthmatic response (asthmatic attack, 2 cases) and adverse events (tremor, 1 case) due to a switch from a brand-name tulobuterol tape to a generic tape were recently reported. These changes disappeared after reformulation from generic to the brand-name tape. To investigate this issue, we conducted a questionnaire survey on changes of asthmatic response, adverse events and product usability due to a switch between tulobuterol tapes. We identified 44 cases (18 from doctors, 26 from pharmacists) in which changes of asthmatic response or adverse events had occurred due to a switch between tulobuterol tapes. Aggravation of asthmatic response had occurred in 30 cases and adverse events in 21 cases due to switch from brand-name tulobuterol tape to generic tape. As regards change of product usability, we obtained 96 relevant responses (18 from doctors, 78 cases pharmacists), and the major response was that generic tulobuterol tape peeled off the skin more easily than did the brand-name tape (60 cases). These results suggest that changes of asthmatic response, adverse events and product usability should be carefully monitored when switching tulobuterol tapes.


Gender dimorphism of a visual anomaly: a deductive prediction based on an ethological model.
Using an ethological model, we deduced a prediction concerning gender dimorphism in a visual anomaly from a re-construction of the phylogeny of man. The prediction, which is based on four premises, is that deficits in distance vision (myopia) would be more prevalent in contemporaneous women than in men. Data collected in a de facto double-blind method support the prediction, and thereby support the unique efficacy in using an ethological model to understand facets of the contemporary human condition.


Experiences with the in vivo and in vitro comet assay in regulatory testing.
The in vivo comet assay has recently been implemented into regulatory genotoxicity testing of pharmaceuticals with inclusion into the ICH S2R1 guidance. Regulatory genotoxicity testing aims to detect DNA alterations in form of gene mutations, larger scale chromosomal damage and recombination and aneuploidy. The ICH S2R1 guideline offers two options of standard batteries of tests for the detection of these endpoints. Both options start with an AMES assay and option 1 includes an in vitro mammalian cell assay and an in vivo micronucleus assay in rodent, whereas option 2 includes an in vivo micronucleus assay in bone marrow in rodent and a second in vivo assay in a second tissue with a second endpoint. The test recommended as second in vivo test is the comet assay in rat liver. The in vivo comet assay is considered as mature enough to ensure reliable detection of relevant in vivo genotoxicants in combination with the micronucleus test in bone marrow and the AMES assay. Although lots of research papers have been published using the in vitro comet assay, the in vitro version has not been implemented into official regulatory testing guidelines. A survey of the years 1999-2014 revealed 27 in vivo comet assays submitted to BfArM with market authorisation procedures, European and national advice procedures and clinical trial applications. In three procedures, in vitro comet assays had been submitted within the genetic toxicology packages.


[Structural and functional reorganization of photosynthetic apparatus in cold adaptation of wheat plants].
The structural and functional characteristics of the photosynthetic apparatus (PSA) and the cold resistance of wheat seedlings were studied during low-temperature adaptation. It has been established that large chloroplasts with thylakoid system of "sun type" forme in the mesophyll cells in the early hours of plants hardening. At the same time the functional reorganization of the PSA in the leaves of wheat occurs: content of pigments changes, stabilization of the pigment-protein complexes is observed, non-photochemical quenching of excess energy increases. The stabilization of photosynthesis during cold adaptation occurs due to structural and functional reorganization of the PSA. It is assumed that the reorganization of the PSA is a prerequisite for formation of increased cold resistance of leaf cells, and this, along with other physiological and biochemical changes occurring in cells and tissues of plants, allows the plants to survive in chilling.


Cyst-forming amoebae of the genus Korotnevella (Amoebozoa: Dactylopodida), with description of two new species.
The genus KorotnevellaGoodkov, 1988 (Amoebozoa: Dactylopodida) comprises amoebae with a complex cell coat that include a layer of scales covering the entire cell surface. Until now no Korotnevella species were known to form cysts. Here we describe two new species of genus Korotnevella and provide a light- and electron-microscopic report of encystment in three species (K. stella (Schaeffer, 1926) Goodkov, 1988, K. limbata n. sp. and K. heteracantha n. sp.) of this genus. Korotnevella limbata has two peculiar wide rims along the upper margin of basket scales forming two short spines at their junctions. The basket scales of K. heteracantha are very similar to those of K. bulla, but have a different spine length and a closed latticework basket with polygonal elements. All three studied species have similar cyst wall consisting of three layers. The outer layer contains scales of trophic stage; the middle one includes so called "cyst scales" with meshwork walls; and the inner one is composed of fibrillar material. Cyst structure of this sort appears to be unique for lobose amoebae and probably represents an autapomorphy for genus Korotnevella.


Clinical guidelines versus universal molecular testing: are we ready to choose an optimal strategy for Lynch syndrome identification?
Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common form of inherited colorectal cancer (CRC). Affected individuals need to undergo intensive CRC surveillance, screening for associated cancers, and possibly prophylactic surgery. Clinically-based guidelines have been used as the basis for Lynch syndrome screening in CRC patient populations. More recently, it has been argued that the universal molecular testing strategies should be implemented to increase the identification of patients who should get germline testing for Lynch syndrome. In this issue of American Journal of Gastroenterology, Julie et al. compare the performance of clinical guidelines with a molecular strategy based on universal microsatellite instability (MSI) testing for identifying CRC patients who have Lynch syndrome. Although there is insufficient evidence to support universal molecular testing for all CRC patients at the current time, the study highlights the need for a systematic approach to identify patients with Lynch syndrome. Physicians and health care systems need to do a better job of identifying patients and families with early-onset of CRC and/or a consistent cancer family history so that they may undergo appropriate molecular evaluation, genetic counseling, and cancer risk management.


Test of balanced transparency.
It is implicitly or explicitly assumed in current transparency models that all the parts of a completely transparent surface have the same perceived degree of transparency. In general, the two experiments reported here have shown that this assumption is false. Consequently, any general transparency equation based on this assumption is unjustified. Separate transparency equations for the different parts of a transparent surface are instead justified. This indicates the need for a model of the overall judgment of transparency of these parts. In the second experiment the hypothesis that the judged degree of transparency of a whole transparent surface is a weighted average of the judged degrees of transparency of the different parts of this surface was tested. The results contradict this hypothesis and support the idea that the judgment of transparency of a whole surface and that of its parts depend on different stimulus conditions.


Naphtoquinones and Sesquiterpene Cyclopentenones from the Sponge Smenospongia cerebriformis with Their Cytotoxic Activity.
Two new naphtoquinones (smenocerones A and B, 1 and 2) and four known sesquiterpene cyclopentenones (dactylospongenones A-D, 3-6) were isolated from sponge Smenospongia cerebriformis living in the Eastern Sea of Vietnam. Their chemical structures were determined by high resolution electrospray ionization (HR-ESI)-MS, NMR spectroscopic analysis, and in comparison with the reported data. The chiroptical properties of compounds 3-6 were examined by experiment and theoretical calculation of circular dichroism (CD) spectra to prove their absolute configurations. Compound 2 significantly exhibited cytotoxic activity towards lung carcinoma (LU-1), hepatocellular carcinoma (HepG-2), promyelocytic leukemia (HL-60), breast carcinoma (MCF-7), and melanoma (SK-Mel-2) human cancer cells with IC50 values of 5.5±0.8, 3.2±0.2, 4.0±0.7, 4.1±0.8, and 5.7±1.1 µg/mL, respectively.


Site-directed sulfhydryl labeling of the oxaloacetate decarboxylase Na+ pump of Klebsiella pneumoniae: helix VIII comprises a portion of the sodium ion channel.
Helix VIII of the beta-subunit of the oxaloacetate decarboxylase of Klebsiella pneumoniae contains the functionally important residues betaN373, betaG377, betaS382, and betaR389. Using a functional oxaloacetate decarboxylase mutant devoid of Cys residues in the beta-subunit, each amino acid residue in helix VIII was replaced individually with Cys. Structural and dynamic features of this region were studied by using site-directed sulfhydryl modification of 20 single-Cys replacement mutants with methanethiosulfonate (MTS) reagents in the absence or presence of Na(+) ions. The pattern of accessibility of the MTS reagents from the periplasmic side of helix VIII shows a periodicity which suggests that this region is alpha-helical. In particular, a water-accessible face comprising betaN373, betaG377, betaS382, betaM386, and betaV390 may be part of a Na(+) channel. Cys residues introduced in the cytoplasmically oriented part of helix VIII were accessible to three different water-soluble MTS compounds and therefore believed to be exposed to water on this side of the membrane. Most residues located in the upper part of helix VIII (residues betaN373-betaV381C) were protected by Na(+) ions for inactivation by the MTS reagents. The distinct results on accessibility toward the different MTS reagents obtained in the presence or absence of Na(+) ions may suggest a conformational change upon binding of Na(+) in this region. The betaR389C mutant had a reduced activity and a pH optimum at pH 9, which could be restored to a wild-type pH optimum of 6.5 and to a 400% gain in activity upon chemical modification with 2-aminoethyl methanethiosulfonate.


Early '100,000 lives' participant sees benefits.
Ongoing history of QI efforts lays excellent foundation for collaborative. Small test changes part of processes leading to improvement. Rapid response teams catch small problems before they become large ones.


[The priority contribution of academician A.L. Kursanov's scientific school to the study of oxygen metabolism and anaerobiosis in plants].
The biographical data on scientific activity of Academician A.L. Kursanov are presented. The contribution of A.L. Kursanov and his school to study of oxygen metabolism and plants anaerobiosis is reviewed. Special attention is given to the works on plant respiration, biosynthesis of endogenous water within plants and animals, mechanism of vitamin A biosynthesis and the metabolism of intracellular water studied with 18O methods. The important works of A.L. Kursanov's school that played an essential role in establishing the new brunch of science at the interface of physiology, biochemistry and ecology of plants, focused on the plant anaerobiosis theory are considered in details.


Lifetimes of cagelike water clusters immersed in bulk liquid water: a molecular dynamics study on gas hydrate nucleation mechanisms.
Molecular dynamics simulations were performed to observe the evolution of cagelike water clusters immersed in bulk liquid water at 250 and 230 K. Totally, we considered four types of clusters--dodecahedral (5(12)) and tetrakaidecahedral (5(12)6(2)) cagelike water clusters filled with or without a methane molecule, respectively. The lifetimes of these clusters were calculated according to their Lindemann index (delta) using the criterion of delta> or =0.07. The lifetimes of the clusters at 230 K are longer than that at 250 K, and their ratios are the same as the ratio of structure relaxation times of bulk water at these temperatures. For both the filled and empty clusters, the lifetimes of 5(12)6(2) cagelike clusters are similar to that of 5(12) cagelike clusters. Although the methane molecules indeed make the filled cagelike water clusters live longer than the empty ones, the empty cagelike water clusters still have the chance of being long lived. These observations support the cluster nucleation hypothesis for the formation mechanisms of gas hydrates.


Intimate Relations: Molecular and Immunologic Interactions Between Neisseria gonorrhoeae and HIV-1.
While the global incidence of human immunodeficiency virus (HIV-1) remains well above UNAIDS targets, sexual transmission HIV is surprisingly inefficient. A variety of host, viral and environmental factors can either increase HIV-1 shedding in the infected partner and/or increase mucosal susceptibility of the HIV-1 uninfected partner. Clinical and epidemiological studies have clearly established that Neisseria gonorrhoeae substantially enhances HIV-1 transmission, despite it not being an ulcerative infection. This review will consider findings from molecular, immunologic and clinical studies that have focused on each of these two human-restricted pathogens, in order to develop an integrative model that describes how gonococci can both increase mucosal shedding of HIV-1 from a co-infected person and facilitate virus establishment in a susceptible host.


[Brain imaging in AIDS].
Encephalic diseases remain an important problem in AIDS patients despite improvement in the rate of disease spread. We provide data on the current situation and describe the clinical, pathological and imaging features commonly observed in encephalic diseases in AIDS patients.


[Spontaneous involution of Vestibular Schwannomas].
The majority of vestibular schwannomas have a stable evolution or a progression of size. Some publications report cases of spontaneous involution. We report here the clinical and radiological characteristics of this type of tumor observed in 14 patients showing a spontaneous tumor involution of their vestibular schwannoma. The results showed an incidence of 8 % with an average tumor regression of 50 %. Functionally, a hearing loss was found in all patients, without correlation with the duration of the observational follow-up. There are spontaneously involutive vestibular schwannomas, but tumor regression does not prevent the deterioration of hearing. Patients should be considered as a subset of those receiving observational management.


Dual effect of saikogenin D: in vitro inhibition of prostaglandin E2 production and elevation of intracellular free Ca2+ concentration in C6 rat glioma cells.
To clarify the pharmacological profile of saikogenin D, we examined the effect of saikogenin D on prostaglandin E2 (PGE2) production and intracellular free Ca2+ concentration ([Ca2+]i) in C6 rat glioma cells. Saikogenin D (1-20 microM) inhibited PGE2 production induced by the Ca2+ ionophore A23187 in a concentration-dependent manner with the IC50 of about 3 microM. Saikogenin D did not affect the conversion of arachidonic acid into PGE2 in microsomal preparations. On the other hand, saikogenin D elevated [Ca2+]i in a concentration-dependent manner (10-100 microM) with the EC50 value of about 35 microM in the presence or absence of extracellular Ca2+. These results suggest that saikogenin D possesses a dual effect: an inhibition of A23187-induced PGE2 production without a direct inhibition of cyclooxygenase activity; and an elevation of [Ca2+]i that is attributed to Ca2+ release from intracellular stores.


Effects of thoracic spinal cord stimulation on cardiac autonomic regulation of the sinus and atrioventricular nodes.
Thoracic spinal cord stimulation (SCS) has been used to treat angina pectoris and to produce cardiac autonomic control. We studied the effect of thoracic SCS on sinus node and AV nodal function to test the hypothesis that SCS modulated autonomic regulation of the electrophysiology of these structures. The effects of thoracic SCS on sinus cycle length and AH interval were studied in 47 dogs in five experimental groups: group 1: intact autonomic nerves; group 2: bilateral ansae subclaviae transection and efferent stellate stimulation; group 3: ansae transection, bilateral vagi transection, and efferent stellate stimulation; group 4: bilateral vagi transection and efferent vagal stimulation; and group 5: bilateral vagal stimulation and bilateral ansae subclaviae transection. Under fluoroscopic guidance, the spinal stimulator electrode was advanced to the T1-T2 position and threshold determined by adjusting the output to produce muscle contraction. Parameters were measured at baseline prior to SCS and during SCS, at 90% threshold. Ansae subclaviae and vagi nerves were isolated using standard approaches. Stellate and vagal stimulation were each performed using a constant current stimulator and at three different frequencies. Sinus cycle length and AH intervals (the latter at constant right atrial pacing of 400 msec) were measured with and without SCS at baseline and at each level of nerve stimulation. Nitric oxide was measured using the coronary sinus overflow method, from a luminal balloon catheter placed deep in the coronary sinus. SCS resulted in an increase in sinus cycle length from 507 +/- 23 msec to 544 +/- 22 msec (P = 0.02) and AH interval from 71 +/- 4 msec to 74 +/- 4 msec (P = 0.03). Ansae subclaviae transection had no effect on this increase, while vagal transection eliminated the increase in sinus cycle length and AH with SCS. The increase in these parameters with SCS was maintained during both stellate stimulation (group 2) and vagal stimulation (group 5) across all three levels of neural stimulation. SCS appears to enhance parasympathetic activity, mediated via the vagus. This may have implications for use of thoracic SCS to treat chronic angina and perhaps prevent sudden cardiac death.


Consumer informatics: helping patients to access health information via the Internet.
Now that many patients independently access health information on the World Wide Web (WWW), healthcare professionals are becoming concerned with control and quality of information available there. The technology has the potential to help patients to become more self-sufficient in managing their own health care and outcomes. This paper examines the importance of developing mechanisms to assess the quality and content of health information websites.


[Results of neonatal vaccination against hepatitis B in Frosinone].
Neonates born to HBSAg-positive mothers are at increased risk of HBV, mainly because of perinatal exposure. Since 1985 the HBV Regional prevention and control program of Latium recommends prophylaxis both with HBIG and HBV vaccine at birth for all infants born to HBaAg-positive mothers. From 1-1-80 to 1-5-88 89 neonates (52 males, 37 female) from Local Health Units (U.S.L.) FR 2, 3, 4, 5, 6, 7, 8, 9 have been examined at the Centre for Vaccination against HBV of Frosinone. Prophylaxis was accomplished both by HBIG 1 ml. I.M.) at birth and HBV vaccine (5.5 ml. I.M. of HBVAX) at birth, and at 1 and 6 months. All injections were given in the gluteal muscle. Antibody titer to HBsAg (antiHBs) detectable by RIA was tested 1 month after or by the time of the third injection of vaccine. Non-responders (anti HBs less than 10 mUI/ml) were given an extra dose of vaccine (0.5 ml I.M.). 85 neonates accomplished vaccination receiving three injections of HBVAX; 4 neonates received only one dose as their parents refused to continue vaccination. Two neonates (non-responders) out of 85 required another dose of vaccine, but only one seroconvertion appeared. No serious side effects have been seen: one case of anorexia and one case of low-grade fever, with no need to interrupt or modify immunization schedule. In the present study the prophylactic efficacy of HBV vaccine has been demonstrated providing 98.6% of cases with antiHBs titer greater than or equal to 10 mUI/ml, and 84% of cases with antiHBs titer greater than or equal to 150 mUI/ml.(ABSTRACT TRUNCATED AT 250 WORDS)


Leishmanicidal activity of two canthin-6-one alkaloids, two major constituents of Zanthoxylum chiloperone var. angustifolium.
The crude alkaloidal extract of Zanthoxylum chiloperone stem bark exhibited in vitro activity against various strains of Leishmania ssp. at 100 microg/ml. Two active major constituents were isolated and identified as canthin-6-one and 5-methoxycanthin-6-one. The effect of these compounds was also tested in an in vivo assay using BALB/c mice infected with Leishmania amazonensis. The mice were treated for 5 weeks postinfection with these alkaloids by oral (14 days) or intralesional route (4 days) at 10 mg/kg daily. The reference drug, N-methylglucamine antimonate was administered by subcutaneous injections at 100 mg/kg for 10 days. Intralesional administration of canthin-6-one reduced the parasite burden but not significantly when it was compared with the untreated group, while the reference drug reduced by 91% the parasite loads in the lesion.


Intestinal Barrier Dysfunction Exacerbates Neuroinflammation via the TLR4 Pathway in Mice With Heart Failure.
The present study aimed to investigate alterations in neuroinflammation after heart failure (HF) and explore the potential mechanisms. Male wild-type (WT) and Toll-like receptor 4 (TLR4)-knockout (KO) mice were subjected to sham operation or ligation of the left anterior descending coronary artery to induce HF. 8 weeks later, cardiac functions were analyzed by echocardiography, and intestinal barrier functions were examined by measuring tight junction protein expression, intestinal permeability and plasma metabolite levels. Alterations in neuroinflammation in the brain were examined by measuring microglial activation, inflammatory cytokine levels and the proinflammatory signaling pathway. The intestinal barrier protector intestinal alkaline phosphatase (IAP) and intestinal homeostasis inhibitor L-phenylalanine (L-Phe) were used to examine the relationship between intestinal barrier dysfunction and neuroinflammation in mice with HF. Eight weeks later, WT mice with HF displayed obvious increases in intestinal permeability and plasma lipopolysaccharide (LPS) levels, which were accompanied by elevated expression of TLR4 in the brain and enhanced neuroinflammation. Treatment with the intestinal barrier protector IAP significantly attenuated neuroinflammation after HF while effectively increasing plasma LPS levels. TLR4-KO mice showed significant improvements in HF-induced neuroinflammation, which was not markedly affected by intestinal barrier inhibitors or protectors. HF could induce intestinal barrier dysfunction and increase gut-to-blood translocation of LPS, which could further promote neuroinflammation through the TLR4 pathway.


A review of the genus Baiocis Browne, 1962 (Coleoptera: Curculionidae: Platypodinae), with new species, new synonymy and a key to males.
Six new species of Baiocis Browne, 1962 are described: Baiocis crassiventris Beaver Liu, B. laosi Beaver Liu, B. orientalis Beaver Liu, B. spicatus Beaver Liu, B. spiniventris Beaver Liu, B. sumatranus Beaver Liu, all from the Oriental region. Of the twenty species listed by Wood and Bright (1992) in the genus Baiocis, the following species belong in Crossotarsus Chapuis, 1865: imitatrix Schedl, 1973, kuntzeni (Schedl, 1937) (comb. n.); the following in Platypus Herbst, 1793: angusticeps Schedl, 1942, perangustus Schedl, 1942, seminitens Schedl, 1971, variolosus Schedl, 1942; the following in Treptoplatypus Wood, 1993: pasohensis (Schedl, 1939). The following new synonymy is proposed: Baiocis pernanulus (Schedl, 1935) (=Platypus annularis Schedl, 1975 syn. n.; =Baiocis solomonicus Browne, 1986 syn. n.); Platypus perangustus Schedl, 1942 (= Platypus sindorae Browne, 1980 syn. n.); Platypus transformis Schedl, 1936 (=Platypus angusticeps Schedl, 1942 syn. n.). Lectotypes are designated for Baiocis incisus (Sampson, 1927), and B. sublunaris (Schedl, 1937), and both sexes of the former species are redescribed. A key is given to the males of fifteen species of Baiocis. Two further species are known only from the female.


Reexamination of string phase and shear thickening in simple fluids.
In 1984, Erpenbeck observed a shear-induced alignment of particles into strings in nonequilibrium molecular dynamics simulations of hard spheres. Since then, it has remained unclear if this effect was genuine or if it arose from the use of a thermostat which assumed an incorrect form for the velocity profile. All studies performed up to now have focused on improving the accuracy with which the velocity profile is determined. We propose here a radically different approach: we apply a recently developed configurational expression for the temperature. This expression does not require any knowledge of the streaming velocity profile. Using a configurational thermostat, we show that the string phase is an artifact and we observe a shear-thickening regime, as seen in experiments on concentrated "hard-sphere"-like colloidal dispersions.


Earned print media in advancing tobacco control in Himachal Pradesh, India: a descriptive study.
The Union-Bloomberg Initiative tobacco control projects were implemented in Himachal Pradesh (a hilly state in North India) from 2007 to 2014. The project focused on the establishment of an administrative framework; increasing the capacity of stakeholders; enforcement of legislation; coalition and networking with multiple stakeholders; awareness generation with focus on earned media and monitoring and evaluation with policy-focussed research. This study aimed to systematically analyse all earned print news items related to the projects. In this cross-sectional descriptive study, quantitative content analysis of earned print news items was carried out using predetermined codes related to areas of tobacco control policies. We also carried out a cost description of the hypothetical value of this earned media. The area of the news item in cm2 was multiplied by the average rate of space for the paid news item in that particular newspaper. There were 6348 news items: the numbers steadily increased with time. Focus on Monitoring tobacco use, Protecting people from tobacco smoke, Offering help to quit, Warning about dangers of tobacco, Enforcing a ban on tobacco advertising and promotion, Raising tax on tobacco products was seen in 24, 17, 9, 23, 22 and 3% of news items, respectively. Press releases were highest at 44% and report by correspondents at 24%. Further, 55, 23 and 21% news items focused on smoking, smokeless and both forms of tobacco use, respectively. Sixty-six per cent and 34% news items, respectively, were focused on youth and women. The news items had a hypothetical value of US$1503 628.3, which was three times more than the funds spent on all project activities. In the absence of funding for paid media, the project strategically used earned media to promote tobacco control policies in the state.


RateML: A Code Generation Tool for Brain Network Models.
Whole brain network models are now an established tool in scientific and clinical research, however their use in a larger workflow still adds significant informatics complexity. We propose a tool, RateML, that enables users to generate such models from a succinct declarative description, in which the mathematics of the model are described without specifying how their simulation should be implemented. RateML builds on NeuroML's Low Entropy Model Specification (LEMS), an XML based language for specifying models of dynamical systems, allowing descriptions of neural mass and discretized neural field models, as implemented by the Virtual Brain (TVB) simulator: the end user describes their model's mathematics once and generates and runs code for different languages, targeting both CPUs for fast single simulations and GPUs for parallel ensemble simulations. High performance parallel simulations are crucial for tuning many parameters of a model to empirical data such as functional magnetic resonance imaging (fMRI), with reasonable execution times on small or modest hardware resources. Specifically, while RateML can generate Python model code, it enables generation of Compute Unified Device Architecture C++ code for NVIDIA GPUs. When a CUDA implementation of a model is generated, a tailored model driver class is produced, enabling the user to tweak the driver by hand and perform the parameter sweep. The model and driver can be executed on any compute capable NVIDIA GPU with a high degree of parallelization, either locally or in a compute cluster environment. The results reported in this manuscript show that with the CUDA code generated by RateML, it is possible to explore thousands of parameter combinations with a single Graphics Processing Unit for different models, substantially reducing parameter exploration times and resource usage for the brain network models, in turn accelerating the research workflow itself. This provides a new tool to create efficient and broader parameter fitting workflows, support studies on larger cohorts, and derive more robust and statistically relevant conclusions about brain dynamics.


Peripancreatic tuberculous lymphadenitis in an immunocompetent patient.
Tuberculosis, an ancient disease continues to be a health care burden in Malaysia in the 21st century. Extrapulmonary tuberculosis is a less common presentation of tuberculosis and in particular peripancreatic tuberculous lymphadenitis is rarely seen. We report a case of a young immunocompetent boy presenting with a two month history of non productive chronic cough associated with loss of appetite and loss of weight. Investigations including CT Scan and Endoscopic ultrasound revealed multiple mediastinal lymphadenopathy and peripancreatic lymphadenopathy with central caseation necrosis. Histology of cervical lymph node was suggestive of tuberculosis and mycobacterium PCR was positive. The patient was subsequently treated with antituberculous therapy and had marked clinical improvement of his symptoms. This case outlines a rare presentation of a common disease and the application of newer investigative tools in making the diagnosis.


Protein secretion and the endoplasmic reticulum.
In a complex multicellular organism, different cell types engage in specialist functions, and as a result, the secretory output of cells and tissues varies widely. Whereas some quiescent cell types secrete minor amounts of proteins, tissues like the pancreas, producing insulin and other hormones, and mature B cells, producing antibodies, place a great demand on their endoplasmic reticulum (ER). Our understanding of how protein secretion in general is controlled in the ER is now quite sophisticated. However, there remain gaps in our knowledge, particularly when applying insight gained from model systems to the more complex situations found in vivo. This article describes recent advances in our understanding of the ER and its role in preparing proteins for secretion, with an emphasis on glycoprotein quality control and pathways of disulfide bond formation.


The importance of pre-freeze equilibration of glycerol in cryopreservation of human spermatozoa and the biochemical conversion of glycerol.
To find optimal conditions for cryopreservation of human spermatozoa with glycerol as cryoprotectant. Pooled semen from groups of three normal donors was allowed to liquefy for 30 minutes at 37 degrees C. Samples were subjected to a prefreeze equilibration interval of 0, 30, or 60 minutes, with 5% or 10% glycerol, at 0 degrees C, 22 degrees C, or 37 degrees C. Samples were frozen in liquid nitrogen for 24 hours, thawed, and assessed for post-thaw motility. Uptake and metabolism of glycerol were studied using [3H] glycerol. Thin-layer chromatography of ethanol extracts of washed spermatozoa that had been incubated with the labeled glycerol was used to determine metabolic products. Overall best cryopreservation was obtained at 37 degrees C with 5% glycerol and 30 minutes' prefreeze incubation. Labeled glycerol was incorporated into both polar and nonpolar metabolites. Two chromatographic peaks were found associated with the spermatozoa, and one peak was found in the incubation medium.


Determinants of outpatients' satisfaction with therapists : relation to outcome.
This study investigated outpatients' satisfaction with therapists, as determined by their perceptions of therapists' behaviors and characteristics, and related patient satisfaction to measures of psychotherapy outcome derived from patients themselves, therapists, and an independent rater. After discharge, 138 demographically and diagnostically heterogeneous patients who had been in psychodynamically oriented psychotherapy returned mailed questionnaires. Therapist characteristics and behaviors such as being likeable, accepting, encouraging, and respectful, helping patients to understand themselves better, and not being "too quiet," as well as overall ratings of satisfaction with therapists, were significantly correlated with patients' ratings of improvement and of help received and with therapists' ratings of outcome.


Level of acuity, severity and intensity of care of adults and older adults admitted to the Intensive Care Unit.
To characterize the level of acuity, severity and intensity of care of adults and older adults admitted to Intensive Care Units and to identify the predictors of severity with their respective predictive capacity according to the age group. A retrospective cohort based on the analysis of medical records of individuals admitted to eight adult intensive care units in the city of São Paulo. The clinical characteristics at admission in relation to severity profile and intensity of care were analyzed through association and correlation tests. The predictors were identified by linear regression and the predictive capacity through the ROC curve. Of the 781 cases (41.1% from older adults), 56.2% were males with a mean age of 54.1 ± 17.3 years. The burden of the disease, the organic dysfunction and the number of devices were the predictors associated with greater severity among adults and older adults, in which the organic dysfunction had the highest predictive capacity (80%) in both groups. Adults and older adults presented a similar profile of severity and intensity of care in admission to the Intensive Care Unit. Organic dysfunction was the factor with the best ability to predict severity in adults and older adults.


Infected by Bias: Behavioral Science and the Legal Response to COVID-19.
This Article presents the first comprehensive analysis of the contribution of behavioral science to the legal response to the COVID-19 pandemic. At the descriptive level, the Article shows how different psychological phenomena such as loss aversion and cultural cognition influenced the way policymakers and the public perceived the pandemic, and how such phenomena affected the design of laws and regulations responding to COVID-19. At the normative level, the Article compares nudges (i.e., choice-preserving, behaviorally informed tools that encourage people to behave as desired) and mandates (i.e., obligations backed by sanctions that dictate to people how they must behave). The Article argues that mandates rather than nudges should serve in most cases as the primary legal tool used to regulate behavior during a pandemic. Nonetheless, this Article highlights ways in which nudges can complement mandates.