Seroepidemiologic studies on Babesia equi and Babesia caballi infections in horses in Jilin province of China.
The prevalence of equine piroplasmosis caused by Babesia equi and Babesia caballi in northeast China has remained unknown, although the People's Republic of China is recognized as an endemic country for the diseases. In the present study, we investigated the prevalence of equine piroplasmosis in Jilin province, a part of northeast China. A total of 111 serum samples were taken from horses in eastern Jilin, and examined for diagnosis of B. equi and B. caballi infections by the enzyme-linked immunosorbent assays with recombinant antigens, equi merozoite antigen-1 and P48, respectively. Of the 111 samples, 38 (34%) and 36 (32%) samples were sero-positive for B. equi infection and B. caballi infection, respectively. In addition, 14 (12%) samples were sero-positive for both B. equi and B. caballi infections. These results indicate that equine piroplasmosis is widespread and therefore a cause for serious concern in northeast China.


Synthesis and immunobiological activity of an original series of acyclic lipid a mimics based on a pseudodipeptide backbone.
Ndelta-L-Homoserinyl-D-ornithinol pseudodipeptides N-acylated with typical Escherichia coli lipid A fatty acid residues and mono-O- or bis-O-phosphorylated have been prepared and their properties investigated. The derivatives carrying two phosphate groups were found to be inducers of NO production. In addition, while they were unable to induce significantly the production of interleukin-6 (IL-6) by human PBMC cells, these compounds behaved also as potent antagonists of LPS-induced IL-6 production in the same human cells system. In conclusion, the molecules described here are the first members of an original class of immunobiologically active lipid A mimics based on an acyclic pseudodipeptide backbone carrying only the essential functionalities of the parent lipid A structure (OM-174). As the products exhibit very low endotoxicity and pyrogenicity, this class of lipid A mimics therefore opens a new generation of immunoadjuvants that possibly could reach clinical applications.


[Functional morphology of thymocytes during physiological fluctuations in hormone balance].
Some metabolic parameters of thymocytes of noninbred female rats were evaluated by quantitative histochemistry during the estrous cycle. There were cyclic variations in the activity of NAD . H and NADP H-diaphorases as well as in the content of DNA and RNA in thymocytes of all parts of the thymus. The greatest range of variations in the content of nucleic acids was recorded in thymocytes of medulla. The activity of acid phosphatase in thymocytes remained unchanged over the period of the estrous cycle.


Trends in Clostridium difficile infection among peripartum women.
With use of the Nationwide Inpatient Sample, we conducted a study to determine whether rates of Clostridium difficile infection for delivery-associated hospitalizations are increasing. From 1998 to 2006, the number and incidence of C. difficile infection among peripartum women increased significantly. These increases were comparable to those observed in the general hospitalized population.


Activity of murine raphe magnus cells predicts tachypnea and on-going nociceptive responsiveness.
In rats, opioids produce analgesia in large part by their effects on two cell populations in the medullary raphe magnus (RM). To extend our mechanistic understanding of opioid analgesia to the genetically tractable mouse, we characterized behavioral reactions and RM neural responses to opioid administration. d-Ala(2), N-Me-Phe(4)-Gly(5)ol-enkephalin, a mu-opioid receptor agonist, microinjected into the murine RM produced cardiorespiratory depression and reduced slow wave electroencephalographic activity as well as increased the noxious heat-evoked withdrawal latencies. As in rat, RM cell types that were excited and inhibited by noxious stimuli, termed on and off cells, respectively, were observed in mice. However, in contrast to findings in rat, opioid doses that suppressed withdrawals did not alter the background discharge rate of murine on and off cells, suggesting that the cellular mechanisms by which the murine RM generates opioid analgesia are substantially different from those in rats. Murine on cell discharge did not predict the latency or magnitude of an ensuing withdrawal but did correlate to the magnitude and latency of concurrent withdrawals. Although opioids failed to alter the background discharge of on and off cells, they reduced the responses of RM neurons to noxious stimulation, further evidence that RM modulates on-going withdrawals. In characterizing the role of RM in respiratory modulation, we found that on cells burst and off cells paused during tachypneic events. The effects of opioids in the murine RM on homeostasis and the association of on and off cell discharge with tachypnea corroborate roles for opioid signaling in RM beyond analgesia.


beta Turns, water cage formation and hydrogen bonding in the structures of L-valyl-L-phenylalanine.
L-Valyl-L-phenylalanine has been crystallized as an orthorhombic dihydrate (1) in the shape of needles and as a monoclinic trihydrate (2) with Z = 16 (P2(1), Z' = 8) in the shape of thin plates. Peptide molecules in these two structures occur in three basic conformations, termed c(1), c(2A) and c(2B). c(2B) has not been observed previously for dipeptides. Together with c(1) it forms a model pair for Type I and Type II beta-turns in protein structures. The crystal packing of (2) is remarkable in that some of the L-Val side chains are exposed to the solvent region of the crystal rather than being located in a hydrophobic layer. The crystal packing thus offers a unique and detailed view of hydrogen-bond cage formation around the hydrophobic groups by the 24 cocrystallized water molecules. The eight [bond]NH(3)(+)...(-)OOC[bond] contacts in the structure are unusually short and the minimum N...O distance of 2.649 (5) A represents a new extreme limit for this type of hydrogen bond in peptide structures.


A national audit of sinus surgery. Results of the Royal College of Surgeons of England comparative audit of ENT surgery.
The results of a national audit of sinus surgery are presented. Forty-six consultant ENT surgeons reported on over 2500 sinus procedures. There has been an exponential rise in the number of surgeons in England and Wales performing functional endoscopic sinus surgery (FESS) in recent years. Sixty-five per cent of surgeons in our study used the FESS technique and 81% had formal or other training. Outpatient sinus endoscopy and CT scans have become more routine pre-operative investigations, whilst the use of plain films has waned. There was a wide variation in the numbers of FESS procedures performed by individual surgeons in the 6-month period (between 5 and 85). The overall complication rate was 0.75% for conventional surgery and 1.41% for functional surgery but no major complications were recorded. The primary symptom of blockage was most successfully treated by both conventional and functional surgery (70% and 84% asymptomatic or improved at 6 months). Pain was relieved in 75% of functional procedures and 47% of conventional procedures and discharge relieved in 76% of FESS procedures and 47% of conventional procedures.


Plasma protein electrophoresis as a prognostic indicator in Aspergillus species-infected Gentoo penguins (Pygoscelis papua papua).
Avian aspergillosis presents a significant threat to captive penguin populations. Currently, a lack of objective prognostic factors limits disease staging, objective reassessment throughout treatment, comparative evaluation of treatment regimes, and appropriate timing of euthanasia. The study objective was to investigate absolute and relative plasma protein fractions by agarose gel electrophoresis (EPH) as predictors of survival in Gentoo penguins (Pygoscelis papua papua) under treatment for aspergillosis. One hundred and eighty-three EPH profiles from individual clinical cases were examined retrospectively. Animal survival to 90 days post sampling was established from clinical records; birds either survived (n = 146) or died within 90 days (n = 37), and time to death was recorded. Fourteen variables showed statistically significant differences (P < .05) between surviving and dying birds. Receiver operating characteristic curve analysis identified total albumin concentration (albumin + prealbumin) and albumin-to-globulin (A:G) ratio as having strongest discriminatory values (95% CI) at 0.788 (0.710-0.866) and 0.784 (0.696-0.871), respectively. Albumin (concentration and percentage of total protein) displayed moderate discriminatory value but additionally a weak positive correlation with time to death (95% CI); r = .353 (0.033-0.608) and .424 (0.116-0.658), respectively. Optimized test cutoffs for total albumins, albumin (concentration and percentage of total protein), and A:G ratio achieved moderate sensitivity and specificity, strong negative predictive values, but weak positive predictive values due to a low prevalence of death. Selection of appropriate test cutoff values may provide valuable adjunctive prognostic tools for clinical decision-making when the prognosis is difficult to assess clinically.


Quantum Spin Dynamics of Individual Neutral Impurities Coupled to a Bose-Einstein Condensate.
We report on spin dynamics of individual, localized neutral impurities immersed in a Bose-Einstein condensate. Single cesium atoms are transported into a cloud of rubidium atoms and thermalize with the bath, and the ensuing spin exchange between localized impurities with quasispin F_{i}=3 and bath atoms with F_{b}=1 is resolved. Comparing our data to numerical simulations of spin dynamics, we find that, for gas densities in the Bose-Einstein condensate regime, the dynamics is dominated by the condensed fraction of the cloud. We spatially resolve the density overlap of impurities and gas by the spin population of impurities. Finally, we trace the coherence of impurities prepared in a coherent superposition of internal states when coupled to a gas of different densities. For our choice of states, we show that, despite high bath densities and, thus, fast thermalization rates, the impurity coherence is not affected by the bath, realizing a regime of sympathetic cooling while maintaining internal state coherence. Our work paves the way toward the nondestructive probing of quantum many-body systems via localized impurities.


Flexible learning program for acoustic consultants.
There is a demand around the world for professional staff to join acoustic consulting companies, and in Australasia this demand is increasing. The extent of acoustics covered in undergraduate programs varies greatly, and there is usually the need to provide additional learning opportunities for new employees. While larger companies may provide training in-house, there are times when they are not in a position to release the senior members to provide such training. By contrast, smaller companies generally do not have this option. Short courses or similar programs can provide the necessary upskilling of new staff, but such courses may not be offered at times or locations that suit the company recruitment program. To overcome the demonstrated need for supplementary education programs in acoustics, the Australasian Association for Acoustical Consultants worked with the University of New South Wales to develop a fully flexible distance learning program, loosely based on the United Kingdom Institute of Acoustics Diploma program. The development, implementation, and experiences from over a decade of offering this program are discussed in this paper.


Computer-assisted identification of potential quinolone derivatives targeting Nipah virus glycoprotein attachment with human cell surface receptor ephrin-B2: Multistep virtual screening.
Nipah Virus (NiV) is a single-stranded, negative-sense, highly lethal RNA virus. Even though NiV has close to 70-80% of mortality in India and Bangladesh, still there is no available US FDA-approved drug or vaccine. NiV attachment glycoprotein (NiV-G) is critical for NiV to invade the human cell where ephrinB2 which is a crucial membrane-bound ligand that acts as a target of NiV. Most of the research has been performed targeting NiV or human ephrin-B to date. Quinolone derivatives are proven scaffolds for many approved drugs used to treat various bacterial, viral respiratory tract, and urinary tract infections, and rheumatologic disorders such as systemic lupus erythematosus, rheumatoid arthritis. Therefore, we have tried to find potential drug molecules employing quinolone scaffold-based derivatives from PubChem targeting both NiV-G and ephrin-B2 protein. A total of 1500+ quinolone derivatives were obtained from PubChem which were screened based on Drug Likeness followed by being subjected to XP docking employing Schrödinger software. The top ten best molecules were then chosen for their absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling based on the docking score ranking. Further, the top five molecules were selected for 200ns molecular dynamics (MD) simulation study with Desmond module followed by MM-GBSA study by Prime module of Schrödinger. The exhaustive analysis leads us to the top three probable lead drug molecules for NiV are PubChem CID 23646770, an analog of PubChem CID 67726448, and PubChem CID 10613168 which have predicted Ki values of 0.480 μm, 0.785 μm, and 0.380 μm, respectively. These proposed molecules can be the future drugs targeting NiV-G and human ephrin-B2 which requires further in vivo validation.


Necrotizing fasciitis of the lower limbs.
We report an uncommon severe soft-tissue infection of the thighs in a male child with acute lymphoblastic leukemia. Early and aggressive medical treatment and the conservative surgical approach were successful. Necrotizing fasciitis should be suspected in any soft-tissue infection until it can be definitely ruled out, since prompt deliver of medical and surgical intervention is essential.


Changes of myelin basic protein in the hippocampus of an animal model of type 2 diabetes.
In this study, we observed chronological changes in the immunoreactivity and expression level of myelin basic protein (MBP), one of the most abundant proteins in the central nervous system, in the hippocampus of Zucker diabetic fatty (ZDF) rats and their control littermates (Zucker lean control; ZLC). In the ZLC group, body weight steadily increased with age; the body weight of the ZDF group, however, peaked at 30 weeks of age, and subsequently decreased. Based on the changes of body weight, animals were divided into the following six groups: early (12-week), middle (30-week), and chronic (52-week) diabetic groups and their controls. MBP immunoreactivity was found in the alveus, strata pyramidale, and lacunosum-moleculare of the CA1 region, strata pyramidale and radiatum of the CA3 region, and subgranular zone, polymorphic layer, and molecular layer of the dentate gyrus. MBP immunoreactivity was lowest in the hippocampus of 12-week-old rats in the ZLC group, and highest in 12-week-old rats in the ZDF group. Diabetes increased MBP levels in the 12-week-old group, while MBP immunoreactivity decreased in the 30-week-old group. In the 52-week-old ZLC and ZDF groups, MBP immunoreactivity was detected in the hippocampus, similar to the 30-week-old ZDF group. Western blot results corroborated with immunohistochemical results. These results suggested that changes in the immunoreactivity and expression of MBP in the hippocampus might be a compensatory response to aging, while the sustained levels of MBP in diabetic animals could be attributed to a loss of compensatory responses in oligodendrocytes.


[The safety of metrological control of applanation tonometers by technical investigations on transfer standards].
According to the German medical devices act and German ordinance on operators of medical devices, human eye tonometers have to be retested every two years. Independent verification laboratories carry out the metrological controls for tonometers which are used by ophthalmogists. Applanation tonometers are frequently used for the accurate measurement of intraocular pressure. For metrological controls these measurement devices are retested by means of test devices (transfer standards) used by verification offices and by private test agencies. PROCEDURE AND METHOD: 25 test devices for applanation tonometers (15 cross-beam balances and 10 force transducer devices), applied for metrological controls by verification offices and by private test agencies, were checked by means of comparative measurements with regard to their quality of measurement and their handling. An applanation tonometer of the type AT 870 (manufacturer: Haag-Streit, Switzerland) served as reference device. Within a measurement range from 9.81 mN to 78.45 mN, upward and downward measurements were performed for the mechanical force of applanation tonometers and for the determination of the reverse span. The investigations for all test devices of applanation tonometers show the compliance within permissible error limits in the observed measuring range for the reverse span with the tonometer AT 870. Some instruments exceed the permissible error limits for test devices for up- and downward force measurements. A comparison concerning the measuring accuracy of two different types of test devices (cross-beam balance and force transducer device) shows that the force transducers tend to have smaller measurement uncertainties. The high metrological demands on test devices for applanation tonometers for the measurement of mechanical force, a prerequisite for accurate calibration and adjustment of this tonometer type, require much experience and special training of the operator handling these standards, in order to minimize subjective error sources. Schoolings with practical trainings for user are recommended to minimize these errors. At least every three years the test devices have to be maintained and recalibrated, in order to guarantee proper function and accuracy of the measurement.


N,N-Dialkyl-2-iodoanilines: a versatile source for the synthesis of Pd(ii) complexes. Synthesis of novel OCP- and CCN-pincer palladium complexes.
The reactivity of a series of N,N-dimethyl-2-iodoanilines bearing different chelating "arms" at the 3-position with Pd(2)(dba)(3) has been explored. 3-[(Diphenylphosphino)methyl]-2-iodo-N,N-dimethylaniline reacted with Pd(2)(dba)(3) and PPh(3) under aerobic conditions to give the OCP-pincer complex , which was formed by sequential C(sp(3))-H activation/oxidation at the alpha-position of the aniline N atom. On the other hand, under similar reaction conditions, 3-[2-(dimethylamino)ethyl]-2-iodo-N,N-dimethylaniline afforded the CCN-pincer complex , after a second C-H activation process at the formyl group of the initially formed OCN-pincer complex. In contrast, 2-iodo-3-(1H-1,2,4-triazol-1-ylmethyl)-N,N-dimethylaniline and 2-iodo-3-(pyrazol-1-ylmethyl)-N,N-dimethylaniline reacted with Pd(2)(dba)(3) and PPh(3), respectively, to give the 6-membered azapalladacycles and , in which the aniline nitrogen is merely a spectator substituent. Finally, treatment of iodide complex with Tl(TfO) afforded the CN-bidentate cationic complex. Solid-state structures of palladium complexes, and CH(2)Cl(2).3CH(3)OH.5H(2)O were determined by X-ray analysis.


A randomized clinical pharmacokinetic trial of Tenofovir in blood, plasma and urine in adults with perfect, moderate and low PrEP adherence: the TARGET study.
Tenofovir disoproxil fumarate (TDF) is key component of pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) for HIV, but existing tools to monitor drug adherence are often inaccurate. Detection of tenofovir (TFV) in accessible biological samples, such as fingerprick blood, urine or oral fluid samples could be a novel objective measure of recent TDF adherence. To measure TFV concentrations associated with different levels of TDF adherence, we designed a randomized clinical trial to assess the blood, urine and oral fluid concentrations of TFV in adults with perfect, moderate and low drug adherence. A randomized, open-label, clinical pharmacokinetic study of tenofovir in healthy adult volunteers without HIV or Hepatitis B infection in Thailand. Consenting, eligible participants are randomized (1:1:1) among three groups to receive a controlled number of TDF (300 mg) doses in a combination pill with emtricitabine (FTC, 200 mg) for six weeks. Participants in Group 1 receive a single TDF/FTC tablet once daily (Perfect adherence); Group 2 receive a single TDF/FTC tablet 4 times/week (Moderate adherence); and Group 3 receive a single TDF/FTC tablet 2 times/week (Low adherence). Blood, plasma, urine and oral fluid samples are collected for drug measurement during three study phases: (i) initial 6-week treatment phase; (ii) intensive 24-h blood sampling phase after 6 weeks; (iii) 4-week washout phase. Thirty adults with evaluable pharmacokinetic samples (10 per group) will be enrolled [based on ensuring 25% precision in pharmacokinetic parameter estimates]. Pre-dose drug concentrations during the treatment phase will be descriptive and comparisons between groups performed using a Kruskal-Wallis test. A non-compartmental pharmacokinetic analysis will be performed on the intensive sampling data at Week 7 and the time course of TFV washout in the difference biological matrices will be reported based on the detected concentrations following drug cessation. The results of this randomized trial will define the target concentration thresholds of TFV in blood, urine and oral fluid that can distinguish between different levels of TDF adherence. Such adherence 'benchmarks' can be applied to real-time drug testing and novel point-of-care tests to identify individuals with poor PrEP or ART adherence. ClinicalTrials.gov Identifier NCT03012607 .


Characterization of novel viral polyproteins detected in cells infected by the flavivirus Kunjin and radiolabelled in the presence of the leucine analogue hydroxyleucine.
Vero cells were infected by Kunjin virus and radiolabelled in the presence of the leucine analogue, threo-beta-hydroxy-DL-leucine (THL). This analogue is known to prevent preprotein processing in cell-free systems when incorporated into signal peptides. Novel Kunjin virus-specified proteins were detected, namely gp140, p120 and gp92; the designations for the proteins indicate their approximate Mr X 10(-3) and whether they are glycosylated. The glycoproteins gp140 and gp92 were observed in cells labelled with [3H]mannose and bound to concanavalin A. Limited proteolytic digestion of gp140, gp92 and gp66 (related to the envelope protein E), and tryptic peptide mapping of these three glycoproteins and p120 indicated that all four were closely related. The glycoproteins gp140 and gp92 were also detected in cells infected by West Nile virus radiolabelled in the presence of THL. Other effects of THL in Kunjin virus-infected cells were a reduction in the incorporation of radioactive amino acids or mannose, a decrease in the yield of haemagglutinin and infectious virus, an inhibition of processing of gp66 to gp53 and an apparent inhibition of synthesis of P98 and P71. We suggest possible explanations for the THL-induced changes in infected cells based on recent models proposed for the synthesis of the yellow fever and West Nile viral proteins.


Maternal exposure to folic acid antagonists and placenta-mediated adverse pregnancy outcomes.
In previous studies, maternal exposure to folic acid antagonists was associated with increased risks of neural tube defects, cardiovascular defects, oral clefts and urinary tract defects. The objective of the current study was to assess the possible effects of using folic acid antagonists in pregnancy on placenta-mediated adverse outcomes of pregnancy. We used data from an administrative database to retrospectively compare the occurrence of placenta-mediated adverse pregnancy outcomes between pregnant women exposed to folic acid antagonists and women without exposure to these agents. We included in the analysis a total of 14 982 women who had been exposed to folic acid antagonists and 59 825 women who had not been exposed. Sulfamethoxazole-trimethoprim was the most frequently prescribed dihydrofolate reductase inhibitor (a total of 12 546 exposures during the preconception period and all 3 trimesters), and phenobarbital was the most frequently prescribed among the other folic acid antagonists (a total of 1565 exposures). The risks of preeclampsia (adjusted odds ratio [OR] 1.52, 95% confidence interval [CI] 1.39-1.66), severe preeclampsia (OR 1.77, 95% CI 1.38-2.28), placental abruption (OR 1.32, 95% CI 1.12-1.57), fetal growth restriction defined as less than the 10th percentile (OR 1.07, 95% CI 1.01-1.13), fetal growth restriction defined as less than the 3rd percentile (OR 1.22, 95% CI 1.11-1.34) and fetal death (OR 1.35, 95% CI 1.07-1.70) were greater among mothers with exposure to folic acid antagonists. In general, the risks associated with exposure to other folic acid antagonists were higher than those associated with exposure to dihydrofolate reductase inhibitors. Supplementary analyses involving tight matching with propensity score, restriction of the analysis to women with exposure during the first and second trimesters and restriction of the analysis to specific categories of folic acid antagonists yielded similar results. Maternal exposure to folic acid antagonists appears to increase the risk of placenta-mediated adverse outcomes of pregnancy.


Direct observation of thitherto unobservable quantum phenomena by using electrons.
Fundamental aspects of quantum mechanics, which were discussed only theoretically as "thought experiments" in the 1920s and 1930s, have begun to frequently show up in nanoscopic regions owing to recent rapid progress in advanced technologies. Quantum phenomena were once regarded as the ultimate factors limiting further miniaturization trends of microstructured electronic devices, but now they have begun to be actively used as the principles for new devices such as quantum computers. To directly observe what had been unobservable quantum phenomena, we have tried to develop bright and monochromatic electron beams for the last 35 years. Every time the brightness of an electron beam improved, fundamental experiments in quantum mechanics became possible, and quantum phenomena became observable by using the wave nature of electrons.


Mechanismbased role of the intestinal microbiota in gestational diabetes mellitus: A systematic review and meta-analysis.
Metabolic disorders caused by intestinal microbial dysregulation are considered to be important causes of gestational diabetes mellitus (GDM). Increasing evidence suggests that the diversity and composition of gut microbes are altered in disease states, yet the critical microbes and mechanisms of disease regulation remain unidentified. PubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), the Web of Science™ (Clarivate™, Philadelphia, PA, USA), and the Cochrane Library databases were searched to identify articles published between 7 July 2012 and 7 July 2022 reporting on case-control and controlled studies that analyzed differences in enterobacteria between patients with GDM and healthy individuals. Information on the relative abundance of enterobacteria was collected for comparative diversity comparison, and enterobacterial differences were analyzed using random effects to calculate standardized mean differences at a p-value of 5%. A total of 22 studies were included in this review, involving a total of 965 GDM patients and 1,508 healthy control participants. Alpha diversity did not differ between the participant groups, but beta diversity was significantly different. Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria were the dominant bacteria, but there was no significant difference between the two groups. Qualitative analysis showed differences between the groups in the Firmicutes/Bacteroidetes ratio, Blautia, and Collinsella, but these differences were not statistically different. Enterobacterial profiles were significantly different between the GDM and non-GDM populations. Alpha diversity in patients with GDM is similar to that in healthy people, but beta diversity is significantly different. Firmicutes/Bacteroidetes ratios were significantly increased in GDM, and this, as well as changes in the abundance of species of Blautia and Collinsella, may be responsible for changes in microbiota diversity. Although the results of our meta-analysis are encouraging, more well-conducted studies are needed to clarify the role of the gut microbiome in GDM. The systematic review was registered with PROSPERO (https://www.crd.york.ac.uk/prospero/) as CRD42022357391.


Isolation of Mycobacterium tuberculosis protein antigens ES-3 1, ES-43 and EST-6 of diagnostic interest from tubercle bacilli by affinity chromatography.
Immunodiagnostically useful M. tuberculosis H37Ra protein antigens ES-31, ES-43 and EST-6 were isolated from detergent soluble sonicate (DSS) antigen using monospecific antibodies by affinity chromatography and compared with similar antigens isolated from M. tuberculosis culture filtrate for seroreactivity in tuberculosis sera by Indirect Enzyme Linked Immunosorbent Assay. Recovery of affinity purified ES-31, ES-43 and EST-6 antigen from DSS antigen was approximately 3, 3.5 and 4% respectively, compared to 10, 9 and 6.3% from culture filtrate. Affinity purified ES-31, ES-43 and EST-6 antigens from both culture filtrate as well as DSS antigen showed similar seroreactivity with overall sensitivity 85, 80 and 75% respectively and specificity of 85% at optimum concentration of 50 pg protein of each antigen. The results suggest that DSS antigen may be a promising antigen source for isolating antigens of diagnostic interest obviating the need for cumbersome, time-consuming culture techniques of mycobacteria.


Polyvalent s-block elements: A missing link challenges the periodic law of chemistry for the heavy elements.
The Periodic Law of Chemistry is one of the great discoveries in cultural history. Elements behaving chemically similar are empirically merged in groups G of a Periodic Table, each element with G valence electrons per neutral atom, and with upper limit G for the oxidation and valence numbers. Here, we report that among the usually mono- or di-valent s-block elements (G = 1 or 2), the heaviest members (87Fr, 88Ra, 119E, and 120E) with atomic numbers Z = 87, 88, 119, 120 form unusual 5- or 6-valent compounds at ambient conditions. Together with well-reported basic changes of valence at the end of the 6d-series, in the whole 7p-series, and for 5g6f-elements, it indicates that at the bottom of common Periodic Tables, the classic Periodic Law is not as straightforward as commonly expected. Specifically, we predict the feasible experimental synthesis of polyvalent [RaL-n] (n = 4, 6) compounds.


Malpractice fears may make ED docs defensive.
You can't eliminate malpractice suits, but you can help make your physicians feel a little less threatened by doing all you can to ensure patient safety. Consider adding a chest pain observation unit, where patients can be monitored for a longer period of time in the ED. Use computerized decision aids that can predict more accurately who will develop signs of ischemia or who has true ischemia. Create a culture of safety where staff feel comfortable enough to voice concerns about potential safety problems.


Lamellar and three-dimensional hybrid compounds formed by cyclohexene- and cyclohexanedicarboxylates of Pb, La, and Cd.
To establish factors that determine the formation of three-dimensional hybrid structures of metal dicarboxylates involving metal-oxygen-metal linkages, we have investigated metal dicarboxylates derived from 1,2-cyclohexene as well as 1,2-, 1,3-, and 1,4-cyclohexane dicarboxylic acids. Thus, we have synthesized a 1,2-cyclohexenedicarboxylate of Cd, [Cd(1,2-CHeDC)(H2O)] (I), a 1,2-cyclohexanedicarboxylate of Pb, [Pb(1,2-CHDC)] (II), and three 1,4-cyclohexanedicarboxylates of La [La2(1,4-CHDC)3(H2O)4] (III), [La3(1,4-HCHDC)2(1,4-CHDC)5(H2O)2].H2O (IV) and [La2(1,4-CHDC)3(H2O)].2.5 H2O (V) under hydrothermal conditions and determined their structures. A mixed dicarboxylate involving both 1,3- and 1,4-cyclohexenedicarboxylates of Pb, [Pb3O(1,3-CHDC)(1,4-CHDC)].0.5 H2O (VI) and a 1,4-cyclohexanedicarboxylate of Pb, [Pb(6)O(2)(1,4-CHDC)3(1,4-HCHDC)2], have also been synthesized and characterized. While the 1,2-dicarboxylates have layered structures, the 1,4-dicarboxylates and the mixed dicarboxylates possess three-dimensional structures. Interestingly, both the 1,2 and 1,4-dicarboxylates are true hybrid compounds composed of infinite M-O-M linkages. The equatorial-equatorial (e,e) conformation is adopted commonly in all these compounds, although less stable conformations are encountered occasionally. The formation of the layered and the three-dimensional structures can be understood based on the relative disposition of the two carboxylic groups, the 1,4-isomer favoring the three-dimensional structure. Based on the results of the present study along with the available literature, we conclude that in order to obtain three-dimensional hybrid structures with metal-oxygen-metal networks, it appears necessary to make use of the 1,4-cyclohexanedicarboxylic acid.


Weil's disease presenting as atypical pneumonia.
Leptospirosis is a disease caused by spp. Leptospira, also known as Weil's disease if it manifests with jaundice. It can be associated with respiratory, renal, hepatic and haematological complications and most importantly carries a high mortality when untreated. We describe a case of a 53 year old man presenting with myalgia and fever in whom the diagnosis of leptospirosis was not initially considered. Following a deterioration in his condition a careful history revealed an apparent brief exposure to animal urine and subsequent grossly positive Leptospira serology. Treatment of his condition led to complete resolution after a brief stay on the intensive care unit. This case highlights the atypical nature of a presentation of Leptospirosis, its respiratory complications, and importance of serological testing in its diagnosis.


Corynebacterium silvaticum sp. nov., a unique group of NTTB corynebacteria in wild boar and roe deer.
A total of 34 Corynebacterium sp. strains were isolated from caseous lymph node abscesses of wild boar and roe deer in different regions of Germany. They showed slow growth on Columbia sheep blood agar and sparse growth on Hoyle's tellurite agar. Cellular fatty acid analysis allocated them in the C. diphtheriae group of genus Corynebacterium. MALDI-TOF MS using specific database extensions and rpoB sequencing resulted in classification as C. ulcerans. Their quinone system is similar to C. ulcerans, with major menaquinone MK-8(H2). Their complex polar lipid profile includes major lipids phosphatidylinositol, phosphatidylinositol-mannoside, diphosphatidylglycerol, but also unidentified glycolipids, distinguishing them clearly from C. ulcerans. They ferment glucose, ribose and maltose (like C. ulcerans), but do not utilise d-xylose, mannitol, lactose, sucrose and glycogen (like C. pseudotuberculosis). They showed activity of catalase, urease and phospholipase D, but variable results for alkaline phosphatase and alpha-glucosidase. All were non-toxigenic, tox gene bearing and susceptible to clindamycin, penicillin and erythromycin. In 16SrRNA gene and RpoB protein phylogenies the strains formed distinct brancheswith C. ulcerans as nearest relative.Whole genome sequencing revealed the unique sequence type 578, a distinctbranch in pangenomic core genome MLST, average nucleotide identities <91%, enhancedgenome sizes (2.55 Mbp) and G/C content (54.4 mol%) compared to related species.These results suggest that the strains represent a novel species, for which wepropose the name Corynebactriumsilvaticum sp. nov., based on their first isolation from forest-dwellinggame animals. The type strain isKL0182T (= CVUAS 4292T = DSM 109166T = LMG 31313T= CIP 111 672T).


Cancer Anxiety Mediates the Association Between Satisfaction With Medical Communication and Psychological Quality of Life After Prophylactic Bilateral Salpingo-Oophorectomy.
Prophylactic Bilateral Salpingo-Oophorectomy (PBSO) reduces the risk of developing ovarian cancer. However, the psychological mechanisms that may affect post-surgery Quality of Life (QoL) among patients who underwent PBSO are still largely unknown. Thus, this study aimed at exploring the direct and indirect associations of satisfaction with medical communication and cancer anxiety on post-surgery QoL among women at high risk of developing ovarian cancer. Fifty-nine women (mean age: 50.64 ± 6.7 years) who underwent PBSO took part in this cross-sectional study, filling out a sociodemographic and clinical questionnaire, a battery of validated psychological measures and an ad hoc developed scale for the assessment of cancer anxiety. We first examined the correlations among all variables of interest, and then tested if cancer anxiety mediated the association between satisfaction with medical communication and post-surgery psychological QoL, controlling both for time from surgery and education. Post-surgery psychological QoL was unrelated from any sociodemographic or clinical variable. Cancer anxiety had a significant direct negative effect on psychological QoL, while satisfaction with medical communication had a significant positive direct effect on it. Finally, cancer anxiety significantly mediated the association between satisfaction with medical communication and post-surgery psychological QoL. Results suggest that post-surgery psychological QoL of patients who underwent PBSO may be increased with interventions, delivered in a genetic counselling setting, targeting quality of medical communication and cancer anxiety.


[Comparative characteristic of cognitive impairment at alcoholic and discirculatory encephalopathy].
Identification of features of cognitive impairment at patients with alcoholic and discirculatory encephalopathy. 30 patients with the alcoholic encephalopathy (AE) and 32 - with discirculatory encephalopathy (DE) participated in research. To patients conducted clinical examination, a computer electroencephalography with determination of cognitive evoked potentials, neuropsychological testing. General and distinguishing characters of a clinical picture, cognitive deficiency, disturbances in the emotional and personal sphere at patients with encephalopathies alcoholic and vascular genesis are established. It is established that a basis of a clinical picture of encephalopathy of various genesis are the cognitive disturbances (CD) and an asthenic syndrome, of AE it is characteristic hyposthenic, and at DE - hyper - and hyposthenic syndromes. Changes of bioelectric activity of a brain at DE had primary localization in occipitoparietal departments of a brain, at AE - in temporal and occipitoparietal assignments. Disorder of categorial thinking, the long-term memory, reciprocal coordination, manual gnosis indicating dysfunction by a frontal, parietal lobe of the left hemisphere, a hippocampus, a corpus collosum are provided to CD in DE and AE patients. It is established that distinguishing characters of CD in AE and DE patients are values of indexes Δ-, β1-, β2-rhythms, the indicators characterizing the impressive speech, volume of visual figurative memory, level of severity of hypochondria.


Re: Madsen et al. "Unnecessary work tasks and mental health: a prospective analysis of Danish human service workers".
Madsen et al (1) recently published a secondary analysis on data provided by the Project on Burnout, Motivation and Job Satisfaction (PUMA). The aim of their study, published in the Scandinavian Journal of Work, Environment & Health was to examine the associations between unnecessary work tasks and a decreased level of mental health. Though the topic was quite novel, reading this work proved disturbing and raised issues. Based on the results of this study, the authors stated that there is an association between unnecessary work tasks (assessed by a single question) and a decreased level of mental health, idem [assessed by the Mental Health Inventory (MHI-5)], in the specific population included in this PUMA survey. The authors point out a limitation of the study, namely that unnecessary work tasks were evaluated using one single question: "Do you sometimes have to do things in your job which appear to be unnecessary?". Semmer defines unnecessary work task as "tasks that should not be carried out at all because they do not make sense or because they could have been avoided, or could be carried out with less effort if things were organized more efficiently" (2). De facto, qualifying what an unnecessary task is requires stating or explaining whether the task makes sense. Making sense or not is not an objective notion. It is very difficult for either a manager or an employee to say if a task is necessary or not. Most important is that it makes sense from the worker's point of view. Making sense and being necessary are not synonyms. Some tasks do not make sense but are economically necessary (eg, when, as physicians, we are reporting our activity using ICD-10 on computers instead of being at patients' bedsides or reading this journal). Thus, there is a wide gap between Semmer's definition and the question used by the authors to evaluate his concept. A secondary analysis based on a single question is not adequate to evaluate unnecessary tasks. Nowadays, the general trend is to reduce the size of questionnaires because they are too long and cannot be used in a routine practice. But an analysis performed on a single question is quite risky: in psychometrics, redundancy is used to confirm a measurement. We lose precision on what exactly we are testing by asking a single question. Madsen et al's results show that among workers saying they are always or often performing unnecessary tasks, the MHI mean score was 74.00 versus 78.20 for people who never or almost never perform unnecessary tasks (P=0.0038). Even though it is a statistically significant result, its clinical relevance is never questioned. What is the impact of losing 4.20 points at MHI test instead of losing 20 points for instance? Statistical difference does not mean clinical relevance. These results show a statistical association, not a causality relationship. The authors did not show that performing unnecessary tasks lowers the level of mental health. It may be the exact opposite. Maybe having poorer mental health (eg, depression, with anhedonia) may make the workers think that what they're doing is useless. In their conclusion, Madsen et al suggest that the elimination of unnecessary work tasks may be beneficial for employees' mental health. To our mind, on the contrary, it may increase psychic suffering. If we suggest to fight unnecessary tasks in workplaces, this may encourage reduction of the margin of manoeuvre (3). The principle of removing unnecessary tasks is part of a Taylorized organization. Some tasks may seem unnecessary or bothersome, but may correspond to work periods that allow for temporary rest. Concretely, in the workplace, managers rather than the employee will be the ones to decide whether a task is useless or not. To improve well-being in the workplace, a global vision of work organization is required. From our point of view, the conclusion drawn from this study should not be that we must eliminate unnecessary tasks, but that we should focus on what makes sense for the worker, with a global view on his work and - as usual - the aim of carrying out further studies on this subject. Conflicts of interest The authors declare no conflict of interest. References 1. Madsen IEH, Tripathi M, Borritz M, Rugulies R, Unnecessary work tasks and mental health: a prospective analysis of Danish human service workers, Scand J Work Environ Health. 2014;40(6):631-8. http://dx.doi.org/10.5271/sjweh.3453. 2. Semmer NK, Tschan F, Meier LL, Facchin S, Jacobshagen N, Illegitimate tasks and counterproductive work behavior, Appl Psychol. 2010;59:70-96. http://dx.doi.org/10.1111/j.1464-0597.2009.00416.x. 3. Durand MJ, Vézina N, Baril R, Loisel P, Richard MC, Ngomo S, Margin of manoeuvre indicators in the workplace during the rehabilitation process: a qualitative analysis, J Occup Rehab. 2009;19:194-202. http://dx.doi.org/10.1007/s10926-009-9173-4.


68Ga-PSMA PET/CT: Joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0.
The aim of this guideline is to provide standards for the recommendation, performance, interpretation and reporting of 68Ga-PSMA PET/CT for prostate cancer imaging. These recommendations will help to improve accuracy, precision, and repeatability of 68Ga-PSMA PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.


Patient-specific finite element models of the human mandible: Lack of consensus on current set-ups.
The use of finite element analysis (FEA) has increased rapidly over the last decennia and has become a popular tool to design implants, osteosynthesis plates and prostheses. With increasing computer capacity and the availability of software applications, it has become easier to employ the FEA. However, there seems to be no consensus on the input variables that should be applied to representative FEA models of the human mandible. This review aims to find a consensus on how to define the representative input factors for a FEA model of the human mandible. A literature search carried out in the PubMed and Embase database resulted in 137 matches. Seven papers were included in this current study. Within the search results, only a few FEA models had been validated. The material properties and FEA approaches varied considerably, and the available validations are not strong enough for a general consensus. Further validations are required, preferably using the same measuring workflow to obtain insight into the broad array of mandibular variations. A lot of work is still required to establish validated FEA settings and to prevent assumptions when it comes to FEA applications.


Cutaneous Granular Cell Tumors in Children: Case Series and Review of the Literature.
Granular cell tumors (GCTs) are uncommon benign neoplasms thought to originate from Schwann cells. They most commonly present in adults as papules or nodules on mucosal sites. The clinical spectrum of GCT in children is not well delineated, although mucosal and cutaneous presentations have been reported. We present three children with cutaneous GCTs and review the literature in an attempt to further characterize this rare pediatric neoplasm.


miR-449a Suppresses Tumor Growth, Migration, and Invasion in Non-Small Cell Lung Cancer by Targeting a HMGB1-Mediated NF-κB Signaling Pathway.
MicroRNAs (miRNAs) have been reported to be involved in many human cancers and tumor progression. The dysregulation of miR-449a is found in many types of malignancies and is associated with tumor growth, migration, and invasion. However, its expression and function in non-small cell lung cancer (NSCLC) still remains unclear. In our study, miR-449a was found to be downregulated in both NSCLC tissues and cell lines, and low miR-449a expression was obviously associated with tumor differentiation, TMN stage, and poor overall survival (OS). Moreover, we demonstrated that miR-449a could inhibit tumor proliferation, migration, and invasion in NSCLC. We also confirmed that HMGB1 was a direct target gene of miR-449a in NSCLC with dual-luciferase reporter assay, and upregulation of HMGB1 could reverse the miR-449a-induced suppression of growth, migration, and invasion in NSCLC cells. Last, we found that miR-449a suppressed tumor initiation and development through the NF-κB signaling pathway. These results indicate that miR-449a functions as a tumor suppressor in NSCLC by targeting the HMGB1-mediated NF-κB signaling pathway in NSCLC.


Tacrolimus, a potential neuroprotective agent, ameliorates ischemic brain damage and neurologic deficits after focal cerebral ischemia in nonhuman primates.
Tacrolimus (FK506), an immunosuppressive drug, is known to have potent neuroprotective activity and attenuate cerebral infarction in experimental models of stroke. Here we assess the neuroprotective efficacy of tacrolimus in a nonhuman primate model of stroke, photochemically induced thrombotic occlusion of the middle cerebral artery (MCA) in cynomolgus monkeys. In the first experiment, tacrolimus (0.01, 0.032, or 0.1 mg/kg) was intravenously administered immediately after MCA occlusion, and neurologic deficits and cerebral infarction volumes were assessed 24 hours after the ischemic insult. Tacrolimus dose-dependently reduced neurologic deficits and infarction volume in the cerebral cortex, with statistically significant amelioration of neurologic deficits at 0.032 and 0.1 mg/kg and significant reduction of infarction at 0.1 mg/kg. In the second experiment, the long-term efficacy of tacrolimus on neurologic deficits and cerebral infarction was assessed. Vehicle-treated monkeys exhibited persistent and severe deficits in motor and sensory function for up to 28 days. A single intravenous bolus injection of tacrolimus (0.1 or 0.2 mg/kg) produced long-lasting amelioration of neurologic deficits and significant reduction of infarction volume. In conclusion, we have provided compelling evidence that a single dose of tacrolimus not only reduces brain infarction but also ameliorates long-term neurologic deficits in a nonhuman primate model of stroke, strengthening the view that tacrolimus might be beneficial in treating stroke patients.


Routine health information utilization and associated factors among health care workers in Ethiopia: A systematic review and meta-analysis.
Utilization of routine health information plays a vital role for the effectiveness of routine and programed decisions. A proper utilization of routine health information helps to make decisions based on evidence. Considerable studies have been done on the utilization of routine health information among health workers in Ethiopia, but inconsistent findings were reported. Thus, this study was conducted to determine the pooled utilization of routine health information and to identify associated factors among health workers in Ethiopia. Search of PubMed, HINARI, Global Health, Scopus, EMBASE, web of science, and Google Scholar was conducted to identify relevant studies from October 24, 2020 to November 18, 2020. The Newcastle-Ottawa scale tool was used to assess the quality of included studies. Two reviewers extracted the data independently using a standardized data extraction format and exported to STATA software version 11 for meta-analysis. Heterogeneity among studies was checked using Cochrane Q and I2 test statistics. The pooled estimate of utilization of routine health information was executed using a random effect model. After reviewing 22924 studies, 10 studies involving 4054 health workers were included for this review and meta-analysis. The pooled estimate of routine health information utilization among health workers in Ethiopia was 57.42% (95% CI: 41.48, 73.36). Supportive supervision (AOR = 2.25; 95% CI: 1.80, 2.82), regular feedback (AOR = 2.86; 95% CI: 1.60, 5.12), availability of standard guideline (AOR = 2.53; 95% CI: 1.80, 3.58), data management knowledge (AOR = 3.04; 95% CI: 1.75, 5.29) and training on health information (AOR = 3.45; 95% CI: 1.96, 6.07) were identified factors associated with utilization of routine health information. This systematic review and meta-analysis found that more than two-fifth of health workers did not use their routine health information. This study suggests the need to conduct regular supportive supervision, provision of training and capacity building, mentoring on competence of routine health information tasks, and strengthening regular feedback at all health facilities. In addition, improving the accessibility and availability of standard set of indicators is important to scale-up information use.


Effects of dietary levels of vitamin A on the egg yield and immune responses of laying hens.
This research, which was designed and carried out as two consecutive experiments, investigated the effects of four different levels (0, 4,000, 12,000, and 24,000 IU/kg) of vitamin A supplementation on egg yield, plasma vitamin A levels, and immune responses of laying hens. Transmission of maternal immunity to their descendants was also studied. In the first experiment, egg yield, blood vitamin A levels, and various parameters of the immune system such as T lymphocyte levels in the peripheral blood, plasma cell counts in the spleen, and antibody titers against Newcastle Disease Virus (NDV) in the sera were investigated for a 1-yr period. A total of 864 Hisex-brown laying hens were used in this experiment. The chicks were reared as commercial flocks until the 18th wk of age. No significant differences occurred among the parameters of the different diet groups. In the second experiment, maternal immunity was assessed in the chickens, supplied by hatching the eggs from hens in the first experiment. Maternal immunity was assayed by using the parameters as in Experiment 1. For this purpose, both blood and tissue samples were taken on the 2nd, 7th, and 10th d posthatch. Vitamin A supplementation had no significant effects on maternally, derived antibody titers or histologic structure of the lymphoid organs.


Systemic Sclerosis Patients Present Alterations in the Expression of Molecules Involved in B-Cell Regulation.
The activation threshold of B cells is tightly regulated by an array of inhibitory and activator receptors in such a way that disturbances in their expression can lead to the appearance of autoimmunity. The aim of this study was to evaluate the expression of activating and inhibitory molecules involved in the modulation of B cell functions in transitional, naive, and memory B-cell subpopulations from systemic sclerosis patients. To achieve this, blood samples were drawn from 31 systemic sclerosis patients and 53 healthy individuals. Surface expression of CD86, MHC II, CD19, CD21, CD40, CD22, Siglec 10, CD35, and FcγRIIB was determined by flow cytometry. IL-10 production was evaluated by intracellular flow cytometry from isolated B cells. Soluble IL-6 and IL-10 levels were measured by ELISA from supernatants of stimulated B cells. Systemic sclerosis patients exhibit an increased frequency of transitional and naive B cells related to memory B cells compared with healthy controls. Transitional and naive B cells from patients express higher levels of CD86 and FcγRIIB than healthy donors. Also, B cells from patients show high expression of CD19 and CD40, whereas memory cells from systemic sclerosis patients show reduced expression of CD35. CD19 and CD35 expression levels associate with different autoantibody profiles. IL-10(+) B cells and secreted levels of IL-10 were markedly reduced in patients. In conclusion, systemic sclerosis patients show alterations in the expression of molecules involved in B-cell regulation. These abnormalities may be determinant in the B-cell hyperactivation observed in systemic sclerosis.


[In vivo sensitivity of Plasmodium falciparum to amino-4-quinolines and sulfadoxine pyrimethamine in Agou (Ivory Coast)].
A comparative study of the in vivo sensitivity of Plasmodium falciparum to amodiaquine versus chloroquine has been made among children in Agou (south Côte d'Ivoire). In case of resistance to these drugs, the association of sulfadoxine-pyrimethamine was administered and followed by a J14 checking. We have noticed: (1) 8.47% of amodiaquine resistance versus 36.96% of chloroquine resistance (all these resistances are from type II), (2) a good clinical efficiency of the 4 amino quinolines. Only 1.69% of the subjects having resistant stocks to amodiaquine have gone feverish down to J7 whereas 10.47% of subjects have clinically resisted to chloroquine, (3) a good tolerance of drugs and an excellent clinical and parasitological efficiency of the second intention treatment. These data are in favour of using first the 4 amino quinolines (particularly the amodiaquine) in the treatment of simple bout of malaria to Plasmodium falciparum in this region. In case of resistance to these drugs, we recommend the combination sulfadoxine-pyrimethamine.


Vascular hyperpermeability as a hallmark of phacomatoses: is the etiology angiogenesis related to or comparable with mechanisms seen in inflammatory pathways? Part II: angiogenesis- and inflammation-related molecular pathways, tumor-associated macrophages, and possible therapeutic implications: a comprehensive review.
Phacomatoses are a special group of familial hamartomatous syndromes with unique neurocutaneous manifestations as well as characteristic tumors. Neurofibromatosis type 2 (NF2) and tuberous sclerosis complex (TSC) are representatives of this family. A vestibular schwannoma (VS) and subependymal giant cell tumor (SGCT) are two of the most common intracranial tumors associated with these syndromes, related to NF2 and TSC, respectively. These tumors can present with an obstructive hydrocephalus due to their location adjacent to or in the ventricles. Remarkably, both tumors are also known to have a unique association with elevated protein concentrations in the cerebrospinal fluid (CSF), sometimes in association with a non-obstructive (communicating) hydrocephalus. Of the two, SGCT has been shown to be associated with a predisposition to CSF clotting, causing a debilitating recurrent shunt obstruction. However, the exact relationship between high protein levels and clotting of CSF remains unclear, nor do we understand the precise mechanism of CSF clotting observed in SGCT. Elevated protein levels in the CSF are thought to be caused by increased vascular permeability and dysregulation of the blood-brain barrier. The two presumed underlying pathophysiological processes for that in the context of tumorigenesis are angiogenesis and inflammation. Both these processes are correlated to the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin pathway which is tumorigenesis related in many neoplasms and nearly all phacomatoses. In this review, we discuss the influence of angiogenesis and inflammation pathways on vascular permeability in VSs and SGCTs at the phenotypic level as well as their possible genetic and molecular determinants. Part I described the historical perspectives and clinical aspects of the relationship between vascular permeability, abnormal CSF protein levels, clotting of the CSF, and communicating hydrocephalus. Part II hereafter describes the different cellular and molecular pathways involved in angiogenesis and inflammation observed in both tumors and explores the existing metabolic overlap between inflammation and coagulation. Interestingly, while increased angiogenesis can be observed in both tumors, inflammatory processes seem significantly more prominent in SGCT. Both SGCT and VS are characterized by different subgroups of tumor-associated macrophages (TAMs): the pro-inflammatory M1 type is predominating in SGCTs, while the pro-angiogenetic M2 type is predominating in VSs. We suggest that a lack of NF2 protein in VS and a lack of TSC1/TSC2 proteins in SGCT significantly influence this fundamental difference between the two tumor types by changing the dominant TAM type. Since inflammatory reactions and coagulation processes are tightly connected, the pro-inflammatory state of SGCT may also explain the associated tendency for CSF clotting. The underlying cellular and molecular differences observed can potentially serve as an access point for direct therapeutic interventions for tumors that are specific to certain phacomatoses or others that also carry such genetic changes.


Compact and Low-Complexity Binary Feature Descriptor and Fisher Vectors for Video Analytics.
In this paper, we propose a compact and low-complexity binary feature descriptor for video analytics. Our binary descriptor encodes the motion information of a spatio-temporal support region into a low-dimensional binary string. The descriptor is based on a binning strategy and a construction that binarizes separately the horizontal and vertical motion components of the spatio-temporal support region. We pair our descriptor with a novel Fisher Vector (FV) scheme for binary data to project a set of binary features into a fixed length vector in order to evaluate the similarity between feature sets. We test the effectiveness of our binary feature descriptor with FVs for action recognition, which is one of the most challenging tasks in computer vision, as well as gait recognition and animal behavior clustering. Several experiments on the KTH, UCF50, UCF101, CASIA-B, and TIGdog datasets show that the proposed binary feature descriptor outperforms the state-of-the-art feature descriptors in terms of computational time and memory and storage requirements. When paired with FVs, the proposed feature descriptor attains a very competitive performance, outperforming several state-of-the-art feature descriptors and some methods based on convolutional neural networks.


Enrichment of colorectal cancer stem cells through epithelial-mesenchymal transition via CDH1 knockdown.
Cancer stem cells (CSCs) are considered to be the origin of cancer relapse and metastasis. The better understanding of CSCs, including CSCs in human colorectal cancer (CRC), may facilitate prevention and treatment. This study aimed to establish a CSC enrichment model via the induction of epithelial-mesenchymal transition (EMT) in CRC cells. We established an EMT model using the SW480 CRC cell line by CDH1 knockdown using shRNA interference. CD24+CD44+ cells were enriched in the CDH1 knockdown cells. The cells exhibited mesenchymal morphology and expressed high levels of EMT-related proteins, which confirmed that these cells had undergone EMT. Our results further showed that the proliferation rate of the transfected cells was reduced, whereas their colony-forming capacity and tumorigenesis in vivo was significantly enhanced compared to the control cells. In conclusion, these cells were highly enriched CSCs (compared to normal CSCs) and may be used as a stable model for cancer research and anticancer drug screening.


Coherent 420 nm light generated by the cavity-enhanced four-wave mixing process in Rb vapor.
We have generated a stable and continuously tunable single frequency (420 nm) coherent blue light (CBL) by the cavity-enhanced four-wave mixing process in Rb vapor. With the bow-tie-type ring cavity, the output power was 3.3 mW, two orders of magnitude higher than that of the CBL generated by the single-pass four-wave mixing process. The measured power stabilities of the 420 nm CBL operated at 2.5 mW and 1.5 mW for 1000 s were 2.89% and 1.88%, respectively. Under the scanning pump laser frequency, the continuously tunable range of the generated CBL reached 1.68 GHz without mode hopping. The measured beam qualities of the generated laser were Mx2=1.117 and My2=1.179. The excellent performance of the 420 nm CBL was characterized by velocity transfer spectroscopy with 780 nm probe laser. This high quality short wavelength coherent light is potentially applicable to photon-atom interactions in quantum optics and fundamental research fields.


Allelic loss but absence of mutations in the polyspecific transporter gene BWR1A on 11p15.5 in hepatoblastoma.
Chromosomal region 11p15.5 shows frequent maternal allelic loss in embryonal tumors, including rhabdomyosarcoma (RMS), Wilms' tumor (WT) and hepatoblastoma (HB), consistent with the presence of at least one tumor suppressor gene in this region, which should be paternally imprinted, i.e., expressed from the maternal allele only. The BWR1A gene encodes a polyspecific transmembrane transporter and is located on 11p15.5. It is highly expressed in liver, paternally imprinted and was found to be mutated in an RMS cell line, making it a plausible tumor suppressor gene for HB. We therefore screened 62 HBs, 3 HB cell lines and 1 pediatric hepatocellular carcinoma for BWR1A mutations using single-strand conformation polymorphism analysis. Allelic loss on 11p15.5 was assessed by PCR-based microsatellite analysis in 56 of the cases for which constitutional DNA was available. BWR1A mRNA expression was determined in 14 HBs by differential RT-PCR of matched cDNA samples from tumor and normal liver. Western blot analysis was performed on 4 tumors and matching normal liver tissue. Except for sequence polymorphisms (in exons 2, 3 and 10 as well as in introns 6 and 7), no mutations were found. Thirteen HBs (23%) had allelic loss on 11p15.5; this included BWR1A in 12 but it was telomeric to BWR1A in 1. Expression of BWR1A mRNA was reduced in 11 out of 14 cases by 19-92%, independent from allelic loss of 11p15.5. By Western blot analysis, all 4 tumors and matching liver samples displayed a 48-51 kd band corresponding to BWR1A. These results make it unlikely that BWR1A is the target of the allelic deletions in HB. However, similar to the putative 11p15.5 tumor suppressor H19, BWR1A appears to be reduced in expression. Reduced expression in the absence of mutations may contribute to HB development; however, to understand the significance of this finding will require further studies on the function of BWR1A, specifically its role in liver development.


Relative effectiveness of mating success and sperm competition at eliminating deleterious mutations in Drosophila melanogaster.
Condition-dependence theory predicts that sexual selection will facilitate adaptation by selecting against deleterious mutations that affect the expression of sexually selected traits indirectly via condition. Recent empirical studies have provided support for this prediction; however, their results do not elucidate the relative effects of pre- and postcopulatory sexual selection on deleterious mutations. We used the Drosophila melanogaster model system to discern the relative contributions of pre- and postcopulatory processes to selection against deleterious mutations. To assess second-male ejaculate competition success (P2; measured as the proportion of offspring attributable to the experimental male) and mating success, mutant and wild-type male D. melanogaster were given the opportunity to mate with females that were previously mated to a standard competitor male. This process was repeated for males subjected to a diet quality manipulation to test for effects of environmentally-manipulated condition on P2 and mating success. While none of the tested mutations affected P2, there was a clear effect of condition. Conversely, several of the mutations affected mating success, while condition showed no effect. Our results suggest that precopulatory selection may be more effective than postcopulatory selection at removing deleterious mutations. The opposite result obtained for our diet manipulation points to an interesting discrepancy between environmental and genetic manipulations of condition, which may be explained by the multidimensionality of condition. Establishing whether the various stages of sexual selection affect deleterious mutations differently, and to what extent, remains an important issue to resolve.


Solution-Processable Balanced Ambipolar Field-Effect Transistors Based on Carbonyl-Regulated Copolymers.
It is very important to develop ambipolar field effect transistors to construct complementary circuits. To obtain balanced hole- and electron-transport properties, one of the key issues is to regulate the energy levels of the frontier orbitals of the semiconductor materials by structural tailoring, so that they match well with the electrode Fermi levels. Five conjugated copolymers were synthesized and exhibited low LUMO energy levels and narrow bandgaps on account of the strong electron-withdrawing effect of the carbonyl groups. Polymer thin film transistors were prepared by using a solution method and exhibited high and balanced hole and electron mobility of up to 0.46 cm2 V-1 s-1 , which suggested that these copolymers are promising ambipolar semiconductor materials.


Orbital implant exposure treatment with porcine dermal collagen patching.
To present a small case series of orbital implant exposures treated with porcine dermal collagen (Permacol, Tissue Science Laboratories PLC, Aldershot, Hants, UK) patching. A retrospective chart review of three cases of orbital implant exposure treated with Permacol patching. Three cases were identified. There were 4 operative episodes of Permacol patching (one socket had two attempts at permacol patching). In all 4 cases the patch rapidly failed and melted away leaving behind the orbital implant exposure. All 3 patients required implant removal. Orbital implant exposure remains a major long-term complication of evisceration and enucleation procedures. On the basis of our experience, we would not recommend using Permacol as a non-autologous material for covering exposed Medpor (Medpor, Porex Surgical, Atlanta, Georgia, USA) orbital implants. Further study is required to fully assess the safety and efficacy profile of Permacol in socket surgery.


Diester-containing Zwitterionic Gemini Surfactants with Different Spacer and Its Impact on Micellization Properties and Viscosity of Aqueous Micellar Solution.
A series of diester containing zwitterionic gemini surfactants, N,N-dimethyl-N-alkyl-2-[[hydroxy (alkoxy) phosphinyl]oxy]-alkylammonium designated as C8(-)-S-Cn(+), S = 2 and 3, n = 12, 14 and 16, were synthesized and characterized by instrumental techniques namely FT-IR, (1)H NMR, (13)C NMR, (31)P NMR and Mass spectral studies. These new gemini surfactants further investigated for their various surfactant properties. The critical micelle concentration (cmc) and the effectiveness of surface tension reduction (Πcmc) were determined as a function of surfactant concentration by means of surface tension measurement. Micellization and viscosity properties were investigated by surface tension, electrical conductivity, dye micellization and rheology techniques. The findings of the aqueous surfactant system obtained were impacted by polarity, size and the nature of zwitterions as the surface. The thermodynamic and viscosity properties of these surfactants found to be based on the structures of gemini surfactants.


Clinical and radiological outcomes of axial lumbar interbody fusion.
Axial lumbar interbody fusion is a novel percutaneous alternative to common open techniques, such as anterior, posterior, and transforaminal lumbar interbody fusion. This minimally invasive technique uses the presacral space to access the L5-S1 and L4-L5 disk space. The goal of this study was to examine outcomes following axial lumbar interbody fusion. The charts of all patients who underwent axial lumbar interbody fusion surgery at our institution between 2006 and 2008 were reviewed. Clinical outcomes included visual analog scale (VAS) and Oswestry Disability Index (ODI). Radiographs were also evaluated for disk space height, L4-L5 and/or L5-S1 Cobb angle, and fusion. Of the 50 patients (32 women, 18 men; mean age, 49.29 years) treated with axial lumbar interbody fusion, 48 had preoperative VAS scores and 16 had preoperative ODI scores available. Complete radiographic data were available at the preoperative, initial postoperative, and final postoperative time points for 46 patients (92%). At last follow-up (average, 12 months), ODI scores were reduced from 46 to 22, and VAS scores were lowered from 8.1 to 3.6. Of the 49 patients with postoperative radiographs, 47 (96%) went on to a solid fusion. There were no significant differences between pre- and postoperative disk space height and lumbar lordosis angle. The most common complications were superficial infection and pseudoarthrosis. Other complications were rectal injury, hematoma, and irritation of a nerve root by a screw. Overall, we found the axial lumbar interbody fusion procedure in combination with pedicle screw placement to have good clinical and radiological outcomes.


Cutoff level of prostate volume to predict the efficacy of α1-D/A adrenoceptor antagonist, naftopidil.
In lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) patients, prostate volume (PV) at baseline affects the improvement of International Prostate Symptom Score voiding symptoms (IPSS-VS) by naftopidil (NAF), but not total IPSS (IPSS-TS). To predict the efficacy of NAF, the PV cutoff point was examined using IPSS-VS. Seventy-seven patients with LUTS/BPH were administrated with NAF 50 mg/day for 4 weeks. Age, PV, IPSS, IPSS quality-of-life (IPSS-QoL), and maximum flow rate (MFR) were evaluated at baseline, and IPSS, IPSS-QoL, and MFR were evaluated after the treatment (at 4 weeks). Responders and nonresponders were divided by IPSS-VS at 4 weeks, and the PV cutoff point was calculated. At baseline, the mean age and PV were 70.7 ± 8.2 years (range, 54-88 years) and 43.3 ± 24.5 mL (range, 20.6-141.7 mL), respectively. After 4 weeks, area under the receiver operating characteristic curve was largest in the patients with <4 points of IPSS-VS. The best standard value to evaluate the efficacy IPSS-VS at 4 weeks was 4 points for the NAF treatment, and the best PV cutoff point was 37.3 mL (sensitivity 60.5%, specificity 71.9%). PV at baseline was one of the predictive factors which affected the efficacy of NAF for IPSS-VS, and LUTS/BPH patients who had PV more than 37.3 mL indicated poor improvement of IPSS-VS, even if IPSS-TS was improved.


Age-related symptom and life quality changes in women with irritable bowel syndrome.
To explore age-related changes in symptoms and quality of life (QoL) of women with irritable bowel syndrome (IBS). Two-hundred and fifty-four female adult outpatients with IBS attending the Department of Gastroenterology at the First Affiliated Hospital of Nanjing Medical University between January, 2008 and October, 2008 were approached. Patients with a history of abdominal surgery, mental illness or those who had recently taken psychotropic drugs were excluded. A physician obtained demographic and abdominal symptom data. All patients were asked to complete the Zung Self-Rated Anxiety and Depression Scale (SDS/SAS) and the IBS-specific QoL questionnaire. The patients were divided into six groups according to age, in 10-year increments: 18-27 years, 28-37 years, 38-47 years, 48-57 years, 58-67 years and 68-75 years (maximum 75 years). Age-related differences of abdominal pain or discomfort were analyzed using rank-sum tests. Differences in SDS/SAS and IBS-QoL scores between age groups were analyzed using one-way analysis of variance. Pearson's correlations evaluated potential associations between IBS symptoms, psychological factors and QoL in each age group. There were no differences in the distribution of IBS subtypes between age groups (χ(2) = 20.516, P = 0.153). Differences in the severity of abdominal pain/discomfort with age were statistically significant (χ(2) = 25.638, P < 0.001); patients aged 48-57 years, 58-67 years or 68-75 years had milder abdominal pain/discomfort than those in the younger age groups. The severity of anxiety or depressive symptoms did not differ between age groups (SDS, χ(2) = 390.845, P = 0.110; SAS, χ(2) = 360.071, P = 0.220). Differences of IBS-QoL scores were statistically significant between age groups (χ(2) = 1098.458, P = 0.011). The scores of patients in the 48-57-year group were lower than those in the 18-27-year and 28-37-year groups (48-57-year group vs 18-27-year group, 74.88 ± 8.76 vs 79.76 ± 8.63, P = 0.021; 48-57-year group vs 28-37-year group, 74.88 ± 8.76 vs 79.04 ± 8.32, P = 0.014). The scores in the 68-75-year group were lower than those in the 18-27-year, 28-37-year and 38-47-year groups (68-75-year group vs 18-27-year group, 71.98 ± 9.83 vs 79.76 ± 8.63, P = 0.003; 68-75-year group vs 28-37-year group, 71.98 ± 9.83 vs 79.04 ± 8.32, P = 0.002; 68-75-year group vs 38-47-year group,71.98 ± 9.83 vs 76.44 ± 8.15, P = 0.039). Anxiety and depression were negatively correlated with QoL in all age groups (SDS and QoL: 18-27-year group, r = -0.562, P = 0.005; 28-37-year group, r = -0.540, P < 0.001; 38-47-year group, r = -0.775, P < 0.001; 48-57-year group, r = -0.445, P = 0.001; 58-67-year group, r = -0.692, P < 0.001; 68-75-year group, r = -0.732, P < 0.001. SAS and QoL: 18-27-year group, r = -0.600, P = 0.002; 28-37-year group, r = -0.511, P < 0.001; 38-47-year group, r = -0.675, P < 0.001; 48-57-year group, r = -0.558, 58-67-year group, P = 0.001; r = -0.588, P < 0.001; 68-75-year group, r = -0.811, P < 0.001). A negative correlation between abdominal pain severity and QoL was found in patients aged more than 58 years (58-67-year group, r = -0.366, P = 0.017; 68-75-year group, r = -0.448, P = 0.048 ), but not in younger patients (18-27-year group, r = 0.080, P = 0.716; 28-37-year group, r = -0.063, P = 0.679; 38-47-year group, r = -0.029, P = 0.812; 48-57-year group, r = -0.022, P = 0.876). Factors affecting QoL should always be treated in IBS, especially emotional problems in young adults. Even mild abdominal pain should be controlled in elderly patients.


Prediction of lung cancer based on serum biomarkers by gene expression programming methods.
In diagnosis of lung cancer, rapid distinction between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) tumors is very important. Serum markers, including lactate dehydrogenase (LDH), C-reactive protein (CRP), carcino-embryonic antigen (CEA), neurone specific enolase (NSE) and Cyfra21-1, are reported to reflect lung cancer characteristics. In this study classification of lung tumors was made based on biomarkers (measured in 120 NSCLC and 60 SCLC patients) by setting up optimal biomarker joint models with a powerful computerized tool - gene expression programming (GEP). GEP is a learning algorithm that combines the advantages of genetic programming (GP) and genetic algorithms (GA). It specifically focuses on relationships between variables in sets of data and then builds models to explain these relationships, and has been successfully used in formula finding and function mining. As a basis for defining a GEP environment for SCLC and NSCLC prediction, three explicit predictive models were constructed. CEA and NSE are frequently- used lung cancer markers in clinical trials, CRP, LDH and Cyfra21-1 have significant meaning in lung cancer, basis on CEA and NSE we set up three GEP models-GEP 1(CEA, NSE, Cyfra21-1), GEP2 (CEA, NSE, LDH), GEP3 (CEA, NSE, CRP). The best classification result of GEP gained when CEA, NSE and Cyfra21-1 were combined: 128 of 135 subjects in the training set and 40 of 45 subjects in the test set were classified correctly, the accuracy rate is 94.8% in training set; on collection of samples for testing, the accuracy rate is 88.9%. With GEP2, the accuracy was significantly decreased by 1.5% and 6.6% in training set and test set, in GEP3 was 0.82% and 4.45% respectively. Serum Cyfra21-1 is a useful and sensitive serum biomarker in discriminating between NSCLC and SCLC. GEP modeling is a promising and excellent tool in diagnosis of lung cancer.


Comparison of terfenadine once daily with terfenadine twice daily for the treatment of perennial allergic rhinitis.
In a double-blind, parallel-group study to compare the efficacy of 120 mg terfenadine taken orally once daily with that of the conventional regimen of 60 mg terfenadine taken twice daily, 30 patients with perennial allergic rhinitis were enrolled. Groups of 15 patients were treated for 7 days with either 60 mg terfenadine twice daily, morning and evening, or 120 mg terfenadine once daily in the morning and placebo in the evening. The physician detected marked to total relief of symptoms (sneezing, rhinorrhoea, nasal pruritus and nasal obstruction) at similar rates (60% and 66%) in the two groups and patients in both groups reported a reduction in symptoms. The incidence of reported side-effects (sedation and mild headache) was low and not significantly different using either regimen. The results indicate that the new once-daily regimen of terfenadine was as effective and as well tolerated as the twice-daily regimen for the treatment of perennial allergic rhinitis.


Describe Molecules by a Heterogeneous Graph Neural Network with Transformer-like Attention for Supervised Property Predictions.
Machine learning and deep learning have facilitated various successful studies of molecular property predictions. The rapid development of natural language processing and graph neural network (GNN) further pushed the state-of-the-art prediction performance of molecular property to a new level. A geometric graph could describe a molecular structure with atoms as the nodes and bonds as the edges. Therefore, a graph neural network may be trained to better represent a molecular structure. The existing GNNs assumed homogeneous types of atoms and bonds, which may miss important information between different types of atoms or bonds. This study represented a molecule using a heterogeneous graph neural network (MolHGT), in which there were different types of nodes and different types of edges. A transformer reading function of virtual nodes was proposed to aggregate all the nodes, and a molecule graph may be represented from the hidden states of the virtual nodes. This proof-of-principle study demonstrated that the proposed MolHGT network improved the existing studies of molecular property predictions. The source code and the training/validation/test splitting details are available at https://github.com/zhangruochi/Mol-HGT.


Effect of habitat complexity on richness, abundance and distributional pattern of forest birds.
Structurally complex forests provide more diverse conditions in comparison to homogenous forests because of greater variety of microhabitats and trees. This study assesses the association of bird species richness, abundance, and distributional pattern with habitat complexity (HC) in Kheyrud Forest in the north of Iran. Birds were surveyed during spring 2009 by 100 point counts. In each point count six habitat features related to the index of HC were computed and scored from 0 to 3. Then the scores were summed and divided into two groups of low and high complexity, HC ≤ 6 and HC > 6, respectively. To compare bird richness and abundance in different HCs, a two sample t-test was used. Presence and absence of bird species at each plot as a dependent variable were compared with the vegetation characteristics as an independent variable by means of the Canonical Correspondence Analysis. The results revealed bird species richness and abundance were significantly higher in more complex habitats. Bird species can be divided into two groups, the first group including species which associated with late successional stages and the second group, species belonging to early successional stages. Numbers of birds belonging to the first group declined in less complex forests, whereas the numbers of birds belonging to the second group increased. At the stand scale, our results reveal that bird abundance and richness are strongly associated with the complexity of vegetation structure in the study area.


Computational Prediction of Protein Epsilon Lysine Acetylation Sites Based on a Feature Selection Method.
Lysine acetylation, as one type of post-translational modifications (PTM), plays key roles in cellular regulations and can be involved in a variety of human diseases. However, it is often high-cost and time-consuming to use traditional experimental approaches to identify the lysine acetylation sites. Therefore, effective computational methods should be developed to predict the acetylation sites. In this study, we developed a position-specific method for epsilon lysine acetylation site prediction. Sequences of acetylated proteins were retrieved from the UniProt database. Various kinds of features such as position specific scoring matrix (PSSM), amino acid factors (AAF), and disorders were incorporated. A feature selection method based on mRMR (Maximum Relevance Minimum Redundancy) and IFS (Incremental Feature Selection) was employed. Finally, 319 optimal features were selected from total 541 features. Using the 319 optimal features to encode peptides, a predictor was constructed based on dagging. As a result, an accuracy of 69.56% with MCC of 0.2792 was achieved. We analyzed the optimal features, which suggested some important factors determining the lysine acetylation sites. We developed a position-specific method for epsilon lysine acetylation site prediction. A set of optimal features was selected. Analysis of the optimal features provided insights into the mechanism of lysine acetylation sites, providing guidance of experimental validation.


Expediting model-based optoacoustic reconstructions with tomographic symmetries.
Image quantification in optoacoustic tomography implies the use of accurate forward models of excitation, propagation, and detection of optoacoustic signals while inversions with high spatial resolution usually involve very large matrices, leading to unreasonably long computation times. The development of fast and memory efficient model-based approaches represents then an important challenge to advance on the quantitative and dynamic imaging capabilities of tomographic optoacoustic imaging. Herein, a method for simplification and acceleration of model-based inversions, relying on inherent symmetries present in common tomographic acquisition geometries, has been introduced. The method is showcased for the case of cylindrical symmetries by using polar image discretization of the time-domain optoacoustic forward model combined with efficient storage and inversion strategies. The suggested methodology is shown to render fast and accurate model-based inversions in both numerical simulations and post mortem small animal experiments. In case of a full-view detection scheme, the memory requirements are reduced by one order of magnitude while high-resolution reconstructions are achieved at video rate. By considering the rotational symmetry present in many tomographic optoacoustic imaging systems, the proposed methodology allows exploiting the advantages of model-based algorithms with feasible computational requirements and fast reconstruction times, so that its convenience and general applicability in optoacoustic imaging systems with tomographic symmetries is anticipated.


Electronic Control on Linear versus Branched Alkylation of 2-/3-Aroylbenzofurans with Acrylates: Combined DFT and Synthetic Studies.
Investigations on the factors that govern unusual branched alkylation of 2-aroylbenzofurans with acrylates by Ru-catalyzed carbonyl-directed C-H activation has been carried out by calculating the kinetics associated with the two key steps-the coordination of the acrylate with the intermediate ruthenacycle and the subsequent migratory insertion reaction-studied with the help of DFT calculations. Eight possible orientations for each mode of alkylation have been considered for the calculations. From these calculations, it has been understood that there is a synergistic operation of the steric and electronic effects favoring the branched alkylation. Further DFT investigations on the alkylation of the isomeric 3-aroylbenzofurans indicated a preference for the linear alkylation and this has been verified experimentally. Overall, the observed/calculated complementary selectivity in the alkylation of 2-/3-aroylbenzofurans with acrylates reveals that the substrate-dependent charge distribution of the Ru-C bond in the intermediate ruthenacycle is an important determining factor and thus the current work opens up a new domain of substrate design for controlling regioselectivity.


Skeletal muscle architectural adaptations to marathon run training.
We assessed lateral gastrocnemius (LG) and vastus lateralis (VL) architecture in 16 recreational runners before and after 12 weeks of marathon training. LG fascicle length decreased 10% while pennation angle increased 17% (p < 0.05). There was a significant correlation between diminished blood lactate levels and LG pennation angle change (r = 0.90). No changes were observed in VL. This is the first evidence that run training can modify skeletal muscle architectural features.


The Kock continent ileostomy--radiology of dysfunctions.
Some patients who have undergone coloproctectomy due to colitis or polyposis with a continent ileostomy constructed ad modum Kock reveal postoperative, secondary abnormalities and dysfunction. The radiological appearance of the pouch in six such patients who complained of incontinence and/or difficulties to catheterize is reported and the findings are correlated with the findings at subsequent surgery and/or endoscopy. It can be concluded that radiology can contribute substantially to the morphodynamic assessment of patients with dysfunction of a Kock ileostomy whereas endoscopy easily depicts mucosal lesions.


Constituents of Chinese propolis and their antiproliferative activities.
Two new flavonoids, 3-O-[(S)-2-methylbutyroyl]pinobanksin (1) and 6-cinnamylchrysin (2), were isolated from the EtOAc-soluble fraction of the MeOH extract of Chinese propolis, along with 12 known compounds (3-14). The structures of the isolated compounds were elucidated on the basis of spectroscopic and chemical analyses. The isolated compounds were tested for their antiproliferative activity toward five different cancer cell lines. Benzyl caffeate (13) and phenethyl caffeate (14) showed potent antiproliferative activity toward tested cell lines with a selective activity toward colon 26-L5 carcinoma cell line (EC(50) values: 13, 1.01; 14, 0.30 microM).


Effect of plant growth promoting bacterium; Pseudomonas putida UW4 inoculation on phytoremediation efficacy of monoculture and mixed culture of selected plant species for PAH and lead spiked soils.
Plant growth promoting bacteria (PGPB) enhanced phytoremediation (PEP) is an attractive remedial strategy for the remediation of polycyclic aromatic hydrocarbon (PAH) and heavy metal (HM) contaminated sites. The effect of PGPB; Pseudomonas putida UW4 inoculation on the phytoremediation efficiency of Medicago sativa, Festuca arundinacea, Lolium perenne, and mixed plants (L. perenne and F. arundinacea) was assessed. This involved two contaminant treatments; "PAH" (phenanthrene; 300 mg·kg-1, fluoranthene; 200 mg·kg-1, and benzo[a]pyrene; 5 mg·kg-1) and "PAH + HM" ('PAH' treatments +100 mg of Pb/kg). PGPB inoculation significantly enhanced root biomass yield of F. arundinacea in PAH treatment, and the mixed plant shoot biomass and L. perenne root biomass yields of the PAH + HM treatment. PGPB significantly enhanced dissipation of phenanthrene and fluoranthene for M. sativa-PAH + PGPB treatment and fluoranthene for F. arundinacea-PAH + HM + PGPB treatment. In others, PGPB inoculation either had no impact or inhibited PAH dissipation. PAH dissipation for the single and mixed plant treatments with PGPB inoculation were not different. The efficiency of PEP is dependent on different factors such as PGPB inoculum biomass, plant species, plant-microbe specificity and type of contaminants. Exploiting PEP technology would require proper understanding of plant tolerance and growth promoting mechanisms, and rhizosphere activities.


miR-16-5p enhances sensitivity to RG7388 through targeting PPM1D expression (WIP1) in Childhood Acute Lymphoblastic Leukemia.
Aim: Given the encouraging results of the p53-Mdm2 inhibitor RG7388 in clinical trials and the vital function of miR-16-5p in suppressing cell proliferation, the aim of the present study was to investigate the combined impact of RG7388 and miR-16-5p overexpression on the childhood acute lymphoblastic leukemia (chALL). Methods: miRTarBase and miRDB, along with KEGG and STRING databases, were used to predict miR-16-5p target genes and explore protein-protein interaction networks, respectively. B- and T-lymphoblastic cell lines, in addition to patient primary cells, were treated with RG7388. Ectopic overexpression of miR-16-5p in Nalm6 cell line was induced through cell electroporation and transfection of microRNA mimics was confirmed by qRT-PCR. Cell viability was evaluated using the MTT assay. Western blot analyses were performed to evaluate the effects of RG7388 and miR-16-5p upregulation on the protein levels of p53 and its downstream target genes in chALL cells. Paired sample t-test was employed for statistical analyses. Results: MTT assay showed RG7388-induced cytotoxicity in wild-type p53 Nalm6 cell line and p53 functional patient primary cells. However, CCRF-CEM and p53 non-functional leukemic cells indicated drug resistance. Western blot analyses validated the bioinformatics results, confirming the downregulation of WIP1, p53 stabilization, as well as overexpression of p21WAF1 and Mdm2 proteins in Nalm6 cells transfected with miR-16-5p. Moreover, enhanced sensitivity to RG7388 was observed in the transfected cells. Conclusion: This is the first study indicating the mechanistic importance of miR-16-5p overexpression in chALL and its inhibitory role in leukemia treatment when combined with the p53-Mdm2 antagonist, RG7388. These findings might be useful for researchers and clinicians to pave the way for better management of chALL.


Regulation by bisoprolol for cardiac microRNA expression in a rat volume-overload heart failure model.
Emerging evidence suggests the involvement of altered microRNA (miRNA) regulation in heart failure pathogenesis. We established a rat volume-overload heart failure model, and examined miRNA expression in normal rats and in the heart failure model, both with and without treatment with bisoprolol. Using miRNA microarrays, we identified 46 differentially expressed miRNAs in the rat heart failure model compared with normal rats. We also identified 18 differentially expressed miRNAs following treatment of normal rats with bisoprolol. Treatment with bisoprolol reversed, to varying degrees, the expression of 10 of the 46 miRNAs whose expression was differentially expressed in the heart failure model. Bioinformatic category analysis of the predicted target genes of these 10 miRNAs suggested that several encode ion-binding proteins. Our results showed that bisoprolol intervention can significantly improve cardiac function and decrease myocardial reconstruction in chronic heart failure. These data suggest that the expression of many miRNAs changes during heart failure, and that bisoprolol may exert its cardioprotective effects in part by reversing the differential expression of some of these genes.


Pair correlation functions of two- and three-dimensional hard-core fluids confined into narrow pores: exact results from transfer-matrix method.
The effect of confinement is studied on the local structure of two- and three-dimensional hard-core fluids. The hard disks are confined between two parallel lines, while the hard spheres are in a cylindrical hard pore. In both cases only nearest neighbour interactions are allowed between the particles. The vertical and longitudinal pair correlation functions are determined by means of the exact transfer-matrix method. The vertical pair correlation function indicates that the wall induced packing constraint gives rise to a zigzag (up-down sequence) shaped close packing structure in both two- and three-dimensional systems. The longitudinal pair correlation function shows that both systems transform continuously from a one-dimensional gas-like behaviour to a zigzag solid-like structure with increasing density.


[Severe acute disseminated encephalomyelitis associated with parainfluenza 3 infection: Case report].
Disseminated encephalomyelitis (ADEM) is an infrequent condition with considerable morbidity and mortality in adult patients. It requires a high level of suspicion and diagnosis emerges by gathering clinical information, laboratory exams and images studies. ADEM is related to an immunological phenomena occurring after a bacterial/viral infection or recent vaccination. Glucocorticoids are the first line treatment, reserving immunoglobulins and plasmapheresis to refractory cases. We report a male patient aged 25, with ADEM associated to parainfluenza 3 virus respiratory infection that required mechanical ventilation and that had a complete recovery only after plasmapheresis.


Exendin-4 potently decreases ghrelin levels in fasting rats.
Ghrelin is a potent orexigenic and adipogenic hormone that strongly influences fat deposition and the generation of hunger in obesity. Indeed, hyperghrelinemia appears to promote an increase in food intake as seen in Prader-Willi Syndrome (PWS). Exendin (Ex)-4 is an agonist of the glucagon-like peptide (GLP)-1 receptor (GLP-1r) that has anorexigenic and fat-reducing properties. Here, we report that Ex-4 reduces the levels of ghrelin by up to 74% in fasted rats. These effects are dose dependent and long lasting (up to 8 h), and they can be detected after both central and peripheral administration of Ex-4. Suppression of ghrelin was neither mimicked by GLP-1(7-36)-NH(2) nor blocked by the GLP-1r antagonist Ex-(9-39). Moreover, it was independent of the levels of leptin and insulin. The decrease in ghrelin levels induced by Ex-4 may explain the reduced food intake in fasted rats, justifying the more potent anorexigenic effects of Ex-4 when compared with GLP-1. As well as the potential benefits of Ex-4 in type 2 diabetes, the potent effects of Ex-4 on ghrelin make it tempting to speculate that Ex-4 could offer a therapeutic option for PWS and other syndromes characterized by substantial amounts of circulating ghrelin.