OsMADS1, a rice MADS-box factor, controls differentiation of specific cell types in the lemma and palea and is an early-acting regulator of inner floral organs.
Grass flowers are highly derived compared to their eudicot counterparts. To delineate OsMADS1 functions in rice floret organ development we have examined its evolution and the consequences of its knockdown or overexpression. Molecular phylogeny suggests the co-evolution of OsMADS1 with grass family diversification. OsMADS1 knockdown perturbs the differentiation of specific cell types in the lemma and palea, creating glume-like features, with severe derangements in lemma differentiation. Conversely, ectopic OsMADS1 expression suffices to direct lemma-like differentiation in the glume. Strikingly, in many OsMADS1 knockdown florets glume-like organs occupy all the inner whorls. Such effects in the second and third whorl are unexplained, as wild-type florets do not express OsMADS1 in these primordia and because transcripts for rice B and C organ-identity genes are unaffected by OsMADS1 knockdown. Through a screen for OsMADS1 targets we identify a flower-specific Nt-gh3 type gene, OsMGH3, as a downstream gene. The delayed transcription activation of OsMGH3 by dexamethasone-inducible OsMADS1 suggests indirect activation. The OsMGH3 floret expression profile suggests a novel role for OsMADS1 as an early-acting regulator of second and third whorl organ fate. We thus demonstrate the differential contribution of OsMADS1 for lemma versus palea development and provide evidence for its regulatory function in patterning inner whorl organs.


Clinical evaluation of S-CMC syrup applied in the treatment of otitis media with effusion. Double blind comparative test with placebo.
We carried out a double blind comparative trial with placebo serving as control using 250 cases of infant otitis media with effusion (OME) in order to objectively evaluate the clinical usefulness of S-carboxymethylcysteine (S-CMC), an oral mucolytic agent, against OME. The results obtained were as follows. 1) Global improvement rate, when judged in items of overall improvement, was 79.8% in S-CMC group and 58.2% in placebo group, S group being significantly better when compared to P. 2) The degree of improvement in each item for evaluation revealed significantly better results in S group compared to P, in both objective findings of the effusion amount and its property, and in audiological findings. 3) Adverse reactions observed in 3 cases (2.5%) in S group and in 2 (1.5%) in P group were not serious, and were eliminated through suspension or discontinuation of the medication. The results obtained suggested the usefulness of S-CMC when used in the treatment of OME.


An unusually large (83 amino acid residues) amyloid fibril protein AA from a patient with Waldenström's macroglobulinaemia and amyloidosis.
The amino acid sequence studies of a human amyloid fibril protein AA derived from a patient with Waldenström's macroglobulinaemia revealed 83 residues. This protein AA was larger than but otherwise very similar to other human AA proteins studied by complete sequencing. Two amino acids were found both in position 52 (Val/Ala) and in position 53 (Trp/Arg), strongly suggesting a polymorphism of AA proteins. Immunologic studies showed the antigenic determinant(s) reacting with antiprotein AA to be located between positions 25 and 76 of the third cyanogen bromide cleavage fragment of the protein.


A 6-hydroxydopamine-induced selective parkinsonian rat model: further biochemical and behavioral characterization.
The main focus of the present study was to define the rotational response of 6-hydroxydopamine-lesioned rats to dopaminergic agonists to separate the partially lesioned rats from those having complete substantia nigra (SN) and ventral tegmental area (VTA) lesions. Animals were challenged by amphetamine and L-DOPA for 10 consecutive weeks. There was a correlation between rotational behavior and extent of midbrain cell loss. Rats with complete SN and < 40% VTA lesion turned more than 5 times/min after amphetamine administration, but not after L-DOPA; animals with complete SN and 40-80% VTA lesions turned vigorously following amphetamine and began turning after L-DOPA administration. Rats with complete SN and VTA lesions turned less after amphetamine than the other two groups, while their turning after L-DOPA administration increased. Extracellular dopamine (DA) measured by microdialysis, intracellular DA measured by postmortem tissue punches, and tyrosine hydroxylase-immunoreactive cell count in SN and VTA were also evaluated. It appears that the dopaminergic cells in the lateral VTA affect DA concentration in the medial caudate nucleus. In the nucleus accumbens of the lesioned side, DA release and metabolism substantially increased with the larger VTA lesion. Dopamine turnover rate in the caudate was also higher in the group with < 40% VTA lesion.


Aggregating post-publication peer reviews and ratings.
Allocating funding for research often entails the review of the publications authored by a scientist or a group of scientists. For practical reasons, in many cases this review cannot be performed by a sufficient number of specialists in the core domain of the reviewed publications. In the meanwhile, each scientist reads thoroughly, on average, about 88 scientific articles per year, and the evaluative information that scientists can provide about these articles is currently lost. I suggest that aggregating in an online database reviews or ratings on the publications that scientists read anyhow can provide important information that can revolutionize the evaluation processes that support funding decisions. I also suggest that such aggregation of reviews can be encouraged by a system that would provide a publicly available review portfolio for each scientist, without prejudicing the anonymity of reviews. I provide some quantitative estimates on the number and distribution of reviews and ratings that can be obtained.


Naringin suppresses the metabolism of A375 cells by inhibiting the phosphorylation of c-Src.
Elevation of glycolysis, increase in lactic acid production, and enhancement of mitochondrial biogenesis are all the changes of energy metabolism of melanoma cells. Melanoma cells' metabolism and energy production networks play an important role in cancer proliferation, survival, motility, invasiveness, metastasis, and angiogenesis. Since the Warburg theory was put forward in the 1930s, more researchers focus on finding new ways for effectively eliminating cancer cells by targeting their energy metabolism. In this study, we found naringin has the inhibitory effects on the glucose metabolism of A375 cells, a melanoma cell line, in a concentration-dependent manner. We also found that naringin could significantly reduce the phosphorylation of c-Src. In summary, we demonstrated that naringin inhibits the malignant phenotype of A375 cells by suppressing c-Src and its downstream signaling pathway. More importantly, we provide the novel mechanism that, as a natural inhibitor of c-Src, naringin could be an effective candidate for the treatment of melanoma.


Efficient autoproteolytic processing of the MHV-A59 3C-like proteinase from the flanking hydrophobic domains requires membranes.
The replicase gene of the coronavirus MHV-A59 encodes a serine-like proteinase similar to the 3C proteinases of picornaviruses. This proteinase domain is flanked on both sides by hydrophobic, potentially membrane-spanning, regions. Cell-free expression of a plasmid encoding only the 3C-like proteinase (3CLpro) resulted in the synthesis of a 29-kDa protein that was specifically recognized by an antibody directed against the carboxy-terminal region of the proteinase. A protein of identical mobility was detected in MHV-A59-infected cell lysates. In vitro expression of a plasmid encoding the 3CLpro and portions of the two flanking hydrophobic regions resulted in inefficient processing of the 29-kDa protein. However, the efficiency of this processing event was enhanced by the addition of canine pancreatic microsomes to the translation reaction, or removal of one of the flanking hydrophobic domains. Proteolysis was inhibited in the presence of N-ethylmaleimide (NEM) or by mutagenesis of the catalytic cysteine residue of the proteinase, indicating that the 3CLpro is responsible for its autoproteolytic cleavage from the flanking domains. Microsomal membranes were unable to enhance the trans processing of a precursor containing the inactive proteinase domain and both hydrophobic regions by a recombinant 3CLpro expressed from Escherichia coli. Membrane association assays demonstrated that the 29-kDa 3CLpro was present in the soluble fraction of the reticulocyte lysates, while polypeptides containing the hydrophobic domains associated with the membrane pelletes. With the help of a viral epitope tag, we identified a 22-kDa membrane-associated polypeptide as the proteolytic product containing the amino-terminal hydrophobic domain.


[Expression of T lymphocyte cytokines in peripheral blood of renal transplant recipients].
To evaluate the clinical values of T-lymphocyte cytokines in renal transplant acute rejection. A total of 31 recipients with renal transplantation and 15 healthy volunteers from January 2010 to January 2012 were enrolled and divided into acute rejection group (n = 11) and stable renal allograft function group (n = 20) according to the inclusion criteria. Peripheral blood was collected from the patients before transplantation, 1, 7, 14, 28 day after transplantation and acute rejection onset. Cytometric bead array (CBA) was used to monitor the levels of interleukin-17 (IL-17), interferon-gamma (IFN-γ), tumor necrosis factor (TNF), interleukin(IL)-10, IL-6, IL-4 and IL-2. The associations of the changes and levels of cytokines in 3 groups were examined with Pearson correlation analysis. The levels of IL-17A, TNF, IL-10 and IL-2 in recipients before transplantation were (3.40 ± 1.29) , (1.79 ± 0.53) , (2.73 ± 0.65) and (1.79 ± 1.02) ng/L respectively and decreased significantly compared to healthy volunteers ((4.52 ± 2.01), (3.36 ± 1.09) , (3.91 ± 0.42) , (3.12 ± 1.07) ng/L respectively, all P < 0.05). However the levels of IFN-γ, IL-6 and IL-4 showed no significant changes between two groups (all P > 0.05). In acute rejection group after transplantation, the levels of IL-17A, IFN-γ, IL-10 and IL-6 were (9.47 ± 4.75) , (5.01 ± 2.23) , (12.20 ± 5.79) , (6.55 ± 3.45) ng/L respectively and increased significantly compared to the renal allograft function group ((4.39 ± 1.26), (2.90 ± 0.87),(5.68 ± 2.25) and (2.10 ± 0.70) ng/L respectively, all P < 0.05); the level of IL-17A was correlated with those of IFN-γ and IL-4 (Pearson r = 0.519, 0.395, both P < 0.01), the level of IFN-γ was correlated with those of IL-4 and IL-2 (r = 0.276, 0.335, all P < 0.05) , the level of TNF was correlated with that of IL-4 (r = 0.423, P < 0.05) and the level of IL-10 was correlated with that of IL-6 (r = 0.361, P < 0.05). Cytokines play an important role in acute rejection of renal transplant. And further understanding of its mechanism may provide experimental and preventive rationales.


Dental fear treatment: comparison of a video training procedure and clinical rehearsals.
Two types of fear desensitization, video training, and clinical rehearsals, were evaluated using psychometric tests, behavioral measures, and interviews for a group of 68 dental fear patients with high and low general trait anxiety. After treatment, a visual analogue scale (VAS) also tested the degree of perceived anxiety before going off to an unknown dentist. Results indicated no significant differences in dental fear reduction effects of the two types of desensitization. However, both treatments showed significant and meaningful effects when compared with a group of 75 dental fear patients on a waiting list who were also tested once at the beginning of the waiting period and again after 6 months. Only high general anxiety subjects resisted desensitization and failed standardized dental treatment tests. Exit interviews revealed that both groups named securing/accepting personnel, conversations about their fears and relaxation, in that order, as the most important factors in their dental fear reduction. Psychometric trust scores confirmed this. VAS scores showed a significant increase in fear level about the next dentist, also indicating trust as a major factor in reducing dental fear. Suggestions are made about which patient conditions can affect the choice of either of these training methods.


Spin-orbit coupling of DFT/MRCI wavefunctions: method, test calculations, and application to thiophene.
During the past decade the one-center mean-field approximation has proven to be a very appropriate framework for the accurate description of spin-orbit effects at the correlated all-electron level. Here, a new efficient code, SPOCK, is introduced that calculates spin-orbit matrix elements in the one-center mean-field approximation for multireference CI wave functions. For the first time, the computation of spin-dependent interactions within a Kohn-Sham orbital based CI (DFT/MRCI) scheme1 is made possible. The latter approach is suitable for large scale systems with up to 100-200 valence electrons. Test calculations are performed on well-known diatomic molecules and the thiocarbonyl pyranthione. Spin-orbit matrix elements show good agreement with their Hartree-Fock orbital based counterparts but are obtained at considerably lower expense, thus demonstrating the power of the method. As an application singlet-triplet couplings in thiophene are investigated that are important for the photophysics and photochemistry. Spin-orbit matrix elements between all pi --> pi* excited states are found to be small. Considerably larger spin-orbit matrix elements are observed only for cases in which pi --> sigma* excited configurations are involved.


[Tobacco-associated cancer : More than just lung cancer].
Tobacco use is the leading preventable cause of cancer and cancer deaths. Tobacco use is not only related to lung cancer, but has an impact on a wide range of different cancer entities in almost every organ system. The aim of this review article is to shed light on the different organ systems involved in tobacco-associated carcinogenesis. For this purpose, first a brief introduction into the topic is given, followed by a detailed description of the different tumor entities associated with tobacco use. Tobacco consumption has been clearly implicated in the causation of many types of cancer, affecting multiple organ systems. Based on current evidence, tobacco use can cause cancer of the mouth and throat, larynx, esophagus, stomach, kidney, pancreas, liver, bladder, cervix, colon and rectum, and acute myeloid leukemia. Tobacco use is not only main cause in the development of lung cancer, but has a major impact in the development of cancer in other organ systems. Therefore, special attention must be given to possible concomitant malignancies when evaluating images of smokers.


Attributable risks associated with hospital outpatient visits for mental disorders due to air pollution: A multi-city study in China.
To determine the associations between outdoor air pollution and hospital outpatient visits for mental disorders in China. We obtained data of 111,842 hospital outpatient visits for mental disorders from the largest hospitals of 13 cities, China, between January 01, 2013 and December 31, 2015. We collected air pollutant data including particulate matter ≤2.5 µm in diameter (PM2.5), particulate matter ≤10 µm in diameter (PM10), nitrogen dioxide (NO2), ozone (O3) and sulphur dioxide (SO2) from China National Environmental Monitoring Centre during the same period. We conducted a time-stratified case-crossover design with conditional logistic regression models to determine the associations. A 10 µg/m3 increase in PM2.5, PM10, NO2 and SO2 was associated with a significant increase in hospital outpatient visits for mental disorders on the current day. When stratified by age, sex and season, the effects of PM2.5 and NO2 were robust among different subgroups at lag05 days. PM10 showed positive associations in males, in cold season, and in depression patients. SO2 showed positive associations in males, in cold season, and in anxiety patients. O3 showed positive associations in females, in warm season, and in depression patients. Nearly one sixth hospital outpatient visits for mental disorders can be attributable to NO2. Short-term increase in PM2.5, PM10, NO2, SO2 and O3 concentrations was significantly associated with exacerbation of mental disorders in China as indicated by increases in hospital outpatient visits. NO2 had more serious health threat than other pollutants in terms of mental disorders. Our findings strongly suggest a need for more strict emission control regulations to protect mental health from air pollution.


RNA-Seq, physiological, and biochemical analysis of burley tobacco response to nitrogen deficiency.
To explore the effects of nitrogen deficiency in burley tobacco, two varieties were cultivated and subjected to conditions of sufficient and deficient nitrogen. The natural characteristics of varieties TN90 and TN86 during tobacco cultivation were similar for nitrogen metabolism. Both carbon and nitrogen metabolism were significantly affected by reducing amounts of applied nitrogen. Under nitrogen-deficient conditions, average leaf biomass, root weight, photosynthetic rate (Pn), pigment levels, total nitrogen, and nitrate content of TN86 and TN90 were significantly decreased by 52.88%, 69.19%, 22.65%, 46.80%, 37.42%, and 79.15%, respectively (p < 0.01). Nicotine and soluble reducing sugar contents were significantly decreased by 96.67% and 95.12%, respectively, in TN86 roots (p < 0.01), which was consistent with the reductions in root surf area, average diameter, and root volume. Nitrogen deficiency induced 6318 differentially expressed genes in both TN90 and TN86, which were highly expressed. In total, 428 upregulated genes were analysed and found to be mainly enriched in the MAPK signalling pathway, sesquiterpenoid and triterpenoid biosynthesis, and arginine and proline metabolism. Meanwhile, 213 downregulated genes were analysed and found to be mainly enriched in photosynthesis, nitrogen metabolism, and amino acid biosynthesis. Reduced pigment content and Pn may result in low carbohydrate formation and decreased leaf biomass in burley tobacco under nitrogen-deficient conditions.


Autoantibodies in Caribbean youth with diabetes mellitus.
The prevalence of diabetes and other autoantibodies in patients with recently diagnosed youth onset diabetes was evaluated. Fifty-seven patients (95% black, age 19 +/- 5 years, 36% male, diabetes duration 2.6 +/- 2.2 years) were clinically diagnosed as having type 1 (n = 35), type 2 (n = 13) and lipoatrophic diabetes (n = 3) while 6 remained untyped. GAD65 was the most common diabetes-associated autoantibody in patients with type 1A diabetes (12/17; 71%). The prevalence of any diabetes-associated autoantibodies decreased with diabetes duration (OR[95%CI]/yr after diagnosis 0.50[0.31,0.82]) and was not associated with age of onset, duration or gender. Rheumatoid factor (13/57; 23%), smooth muscle (6/57; 11%), gastric-parietal cell (5/57; 9%) and thyroid microsomal antibodies (5/57; 9%) were the most frequent non-diabetes associated autoantibodies and were more common in patients with type 1A diabetes. Only one patient had clinical autoimmune disease (hypothyroidism). Type 1A diabetes may constitute up to half the cases of newly diagnosed type 1 diabetes in Jamaican youth and is associated with a higher prevalence of other organ-specific autoantibodies.


Capecitabine-loaded nanoniosomes and evaluation of anticancer efficacy.
Capecitabine (CAP) is an FDA-approved and frequently used chemotherapeutic agent for the treatment of various cancers. However, there are some side effects and chemoresistance limiting its use. Nanotechnological approaches can enhance the efficacy of anticancer drugs. In this study, CAP-loaded nanoniosomes were prepared. Nanoniosomes were prepared by the method of thin film hydration wherein CAP was loaded into the nanoniosomes. Nanoniosomes were then characterized by field emission scanning electron microscopy and (particle) vesicle size analysis. The cytotoxicity effect of the nanoniosomes were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. CAP was loaded into the nanoniosomes and loading capacity and entrapment efficiency were determined. The vesicle size of the nanoniosomes was obtained in the nanometer scale, and CAP release profiles from the nanoniosomes were also obtained. Finally, the cytotoxicity effect of CAP and CAP-loaded nanoniosomes were evaluated toward MCF7 and PANC1 cell lines. The nanoniosomes with an amphipathic structure can penetrate into the cells with an enhanced release rate. These caused the toxicity of drug in the nanoniosomes to be higher than the free drug.


Physiological plasticity of single neurons in auditory cortex of the cat during acquisition of the pupillary conditioned response: II. Secondary field (AII).
The discharges of 22 single neurons were recorded in the secondary auditory cortical field (AII) during acquisition of the pupillary dilation conditioned defensive response in chronically prepared cats. All 22 neurons developed discharge plasticity in background activity, and 21/22 cells developed plasticity in their responses to the acoustic conditioned stimulus (CS). Nonassociative factors were ruled out by the use of a sensitization phase (CS and US [unconditioned stimulus] unpaired) preceding the conditioning phase and by ensuring stimulus constancy at the periphery by neuromuscular paralysis. Changes in background neuronal activity were related to measures of behavioral learning or to changes in the level of arousal. Specifically, decreases in background activity (17/22 cells) developed at the time that subjects began to display conditioned responses. Increases in background activity (5/22) developed in animals that became more tonically aroused during conditioning. However, both increases (11/22) and decreases (10/22) in evoked activity developed independently of the rate of pupillary learning, tonic arousal level, or changes in background activity. These findings indicate that changes in background activity are closely related to behavioral processes of learning and arousal whereas stimulus-evoked discharge plasticity develops solely as a consequence of stimulus pairing. A comparative analysis of the effects of conditioning on secondary and primary (AI) auditory cortex indicates that both regions develop neuronal discharge plasticity early in the conditioning phase and that increases in background activity in primary auditory cortex are also associated with elevated levels of tonic arousal. In addition, the overall incidence of single neurons developing learning-related discharge plasticity is significantly greater in AII than in AI. The relevance of these findings is discussed in terms of parallel processing in sensory systems and multiple sensory cortical fields.


Faked depression: comparing malingering via the internet, pen-and-paper, and telephone administration modes.
The Internet and telephone are valuable resources for mental health practitioners when access to face-to-face assessment or therapy is difficult. However, despite the high stakes (such as access to medication or financial compensation) often involved in psychological testing, little is known about how test administration mode influences test scores when patients are malingering. The aim of this research was to examine for the first time the equivalence of a malingered measure of depression when administered over the Internet, over the telephone, and with pen and paper. A mixed experimental design was used with participants (n=91) randomly allocated to Internet, telephone, or pen-and-paper groups. Participants completed the Edinburgh Depression Scale, first under standard instructions and then under instructions to fake as if experiencing severe depression. A manipulation check was included to ensure participants had understood and followed instructions to fake. As predicted, participants were able to significantly increase their depression scores when asked to fake depression. Participants reported significantly lower faked depression scores over the telephone than in pen-and-paper format. Faked depression scores in the online group did not differ significantly from those in the telephone and pen-and-paper groups. However, participants in all groups met criteria indicative of a provisional diagnosis of depression. Overall, the results indicate that there may be no meaningful difference between malingering across administration modes. If an individual is malingering depression, administration mode has minimal influence. These findings provide preliminary support for the use of online/telephone technologies in the assessment of depression.


Quality of care for ruptured uterus in Sagamu, Nigeria.
A retrospective study was conducted at a Nigerian tertiary hospital to assess the quality of emergency care provided to women managed for a ruptured uterus over an 11-year period. There were 76 cases of ruptured uterus and 4,770 deliveries (1.6%) during the period. Ten women died from a ruptured uterus, giving a case fatality rate of 13.2%. The mean admission-assessment interval by a senior clinician was 48.4 min. The mean decision-laparotomy interval was 6.9 h. Deviations from management protocol were noted in 66 women (86.8%) and underlying reasons were classified as patient-orientated (59.2%), medical personnel (13.2%) and administrative (22.4%) problems. Among women who died, there were more administrative problems, intraoperative and total blood losses were significantly more and preoperative haematocrit was significantly less compared with survivors. The poor quality of care for ruptured uterus in this centre is attributable to patients' financial limitations, which is compounded by administrative problems, particularly those regarding inefficient blood transfusion services. This study demonstrates the urgent need for implementation of a national health insurance scheme at this centre and reiterates the feasibility of employing detailed enquiry of peripartal circumstances to identify specific problems underlying major causes of maternal morbidity and mortality.


[Frequent positivity of the human basophil degranulation test in idiopathic nephrotic syndromes (minimal glomerular changes and segmental and focal glomerulosclerosis)].
Atopic factors play an important role in minimal changes idiopathic nephrotic syndrome ( MCINS ). We therefore studied human basophil degranulation test ( HBDT ) in MCINS and also in patients with segmental and focal glomerulosclerosis ( SFGSNS ) whose relation with MCINS is debated. HBDT was performed with 5 or 6 allergens chosen according to the history of patients and results of cutaneous tests. HBDT was positive in 16 out of 28 MCINS and in 14 among 18 SFGSNS subjects. The difference versus 29 Immune Complex glomerulonephritis and 11 blood donors was significant with the chi 2 test. Because the basophil count was low (less than 10/microliter) in 5 cases, 4 of which had a severe nephrotic syndrome, the HBDT was performed later. The allergen most frequently involved was house dust. This was responsible for a significant degranulation in 10 MCINS (45%) and in 11 SFGSNS (68%) patients; degranulation was obtained more frequently with 2 allergens than with a single one. Obviously such a basophil sensitisation does not prove the responsibility of these allergens.


Sequelae of minor head injury: the natural history of post-concussive symptoms and their relationship to loss of consciousness and follow-up.
The character and natural history of post-concussive symptoms were studied in two subject groups: patients admitted to hospital for observation following brief loss of consciousness (LOC) as a result of head injury and patients who attended the accident unit after head injury but not were not admitted. Follow-up data were obtained from the hospitalized group at standardized out-patient interview and from the non-hospitalized group by postal questionnaire. Two- and 12-week data are presented on 24 hospitalized and 58 non-hospitalized patients. The type and frequency of symptoms was similar in the two groups and rank ordering was significantly correlated. However, the reduction in symptom scores (number of symptoms) 12 weeks post-injury was significantly greater in the hospitalized than the non-hospitalized group. The possible significance of this is discussed.


Identification of the phosphorylated sites of metabolically 32P-labeled osteopontin from cultured chicken osteoblasts.
Osteopontin (OPN) is one of the major secretory phosphoproteins in both calcifying and non-calcifying tissues. Evidence has accumulated for the biological importance of the phosphoproteins and, in particular, the phosphate groups in bone formation, resorption, and calcification. The precise locations of the phosphate groups in the OPN molecule were determined by metabolically labeling OPN with 32P in cultured chicken osteoblasts, followed by purification to homogeneity. N-terminal sequencing showed a single sequence of WPVSKRQHAISA, consistent with that deduced from both cDNA, and previous amino acid sequencing of the protein isolated from chicken bone. Three 32P-labeled peptides were isolated by reverse-phase high performance liquid chromatography of thrombin-digested, 32P-labeled OPN. The N-terminal sequencing of each of these thrombin fragments gave single sequences as follows: WPVSKSRQHAIS, SHHTHRYHQDHVD, and ASKLRKAARKL, with approximate molecular masses of 5, 30, and 20 kDa. These data demonstrate that 32P was incorporated throughout the N- to C-terminal sequence of the protein. Thrombin specifically cleaved chicken OPN at two sites: between Arg-22 and Ser-23, which generated the 5-kDa N-terminal end fragment, and another between Lys-138 and Ala-139, which generated the 30- and 20-kDa fragments. To further define the exact locations of the phosphorylated amino acids and the surrounding amino acid sequences, OPN was digested with trypsin, which generated seven major 32P-labeled peptides whose amino acid sequences were determined. The phosphorylated peptide regions of osteopontin were identified as amino acids 8-18 (QHAIS*AS*S*EEK), 39-54 (LASQQTHYS*S*EENAD), 150-171 (LIEDDAT*AEVGDSQLAGLWLPK), 179-191 (ELAQHQSVENDSR), 194-205 (FDS*PEVGGDSK), 214-219 (ES*LASR), and 239-248 (HSIENNEVTR). The phosphorylated amino acid sites are followed by an asterisk (*). Of the seven identified phosphorylated peptide regions, three were localized on the N-terminal end of the osteopontin molecule (with five phosphorylated serines) and contained the sequence motifs that were phosphorylated by casein kinase II type(s), whereas the remaining four peptides are concentrated toward the C-terminal half of the molecule (with five phosphorylated residues) and contained recognition motifs for other kinases as well as casein kinase II.


Differential binding of Mg2+, Zn2+, and Cd2+ at two sites in a hammerhead ribozyme motif, determined by 15N NMR.
A decamer duplex model of Domain II of the hammerhead ribozyme was synthesized with [8-13C-1,7,NH2-15N3]-guanosine at the known metal binding site, G10.1 and, for comparison, [2-13C-1,7,NH2-15N3]-guanosine at G16.2. The 15N NMR chemical shifts of the labeled N7s monitored during addition of Mg2+, Cd2+, and Zn2+ showed the same preference for binding at G10.1 over G16.2 for each metal. These results demonstrate that 15N labeling can be used to evaluate the binding of different metals, including Mg2+, to a given nitrogen, as well as to compare the binding potential of different sites.


One-Step Process of Mixed Oleic Acid Esters and Its High Temperature Lubrication Properties in Bentonite Gelling Suspension.
In recent years, with the increase in requirements for horizontal wells, ultra-high depth wells, small wells and branching wells, it has become increasingly important to deal with the conflict between drilling safety and bottomhole friction. In order to meet the requirements of complex boreholes and deepwater drilling processes, it is crucial to improve the performance of ester-based lubricants. Oleic acid esters are relatively stable and have high lubricity at low temperature, however, these can be hydrolyzed at high temperature. However, the structure of carboxylic acids and alcohols can significantly affect the performance of synthetic esters. In order to solve the problem of balancing the high-temperature performance and low temperature performance of oleic acid esters with different structures, we propose a new oleic acid esterification process. After mixing methanol and ethylene glycol, it is reacted with oleic acid, and the mixed oleate prepared is named MEO-21, and the optimal esterification conditions are obtained as follows: the reaction time is 3 h, the reaction temperature is 150 °C, and concentrated sulfuric acid is the catalyst. MEO-21 not only achieves an extreme pressure lubrication coefficient reduction rate (Δf) of 86.57% at room temperature, but maintains a stable performance after hot rolling at high temperatures. Hot rolling at 150 °C for 16 h, Δf was 85.25%, hot rolling at 180 °C for 16 h, Δf was 89.56%. MEO-21 was used as a base oil with other industrial by-product oils to compound and produce a high-temperature-resistant lubricant that was named L-541, L-541's Δf was 90.39% at room temperature. L-541 was hot-rolling at 120 °C, 150 °C and 180 °C for 16 h, the Δf was stabled at 89%.


Intraoperative high-dose rate of radioactive phosphorus 32 brachytherapy for diffuse recalcitrant conjunctival neoplasms: a retrospective case series and report of toxicity.
Adjunct treatments for conjunctival malignancies are needed when standard therapy provides limited benefits or fails. To describe the results of patients with diffuse conjunctival neoplasms treated with radioactive phosphorus 32 (32P)-impregnated flexible film. This retrospective case series between January 1, 2010, and January 1, 2013, was conducted at Memorial Sloan-Kettering Cancer Center, a tertiary referral center. The study was conducted on 7 eyes of 6 patients treated for diffuse conjunctival squamous cell carcinoma, sebaceous carcinoma, or lymphoma that had recurrent or residual disease after primary treatment. Patients underwent mapping biopsies and detailed conjunctival drawings to delineate the pathologic extent of the disease. The brachytherapy film used for treatment was the RIC Conformal Source Model 100 (RIC-100, RI Consultants). The RIC-100 is a flexible, thin (approximately 0.5-mm) film made of a polymer chemically bound to 32P. The radioactive 32P film was placed intraoperatively, allowed to stay in place until the prescription dose was reached, and then removed. The median dose at the prescription point (1 mm from the surface of the film) was 15 Gy (range, 5-17 Gy). Patients were tested for best-corrected visual acuity, recurrence-free survival, and adverse events scored by using the Adult Comorbidity Evaluation-27 scale. Between 2010 and 2013, 7 eyes of 6 patients were treated. The median age of patients was 70 years. All patients had a recurrent or persistent neoplasm. Four patients with squamous cell carcinoma, 1 with sebaceous carcinoma, and 1 with metachronous bilateral lymphomas were treated. The median treatment time was 19 minutes (range, 10-52 minutes). The median follow-up was 24.9 months (range, 3.1-38.2 months). Recurrence-free survival 24 months after brachytherapy was 75% (95% CI, 19-89.1). Two moderate adverse events and 1 severe adverse event occurred. Visual acuity was stable or improved in 5 of the 7 eyes (ie, better than 20/70 in the 5 patients who retained their treated eye). Our results show the use of an intraoperative high-dose rate of 32P brachytherapy in selected cases of recalcitrant diffuse conjunctival neoplasms. This technique offers a novel adjunct in the treatment of these cancers. Further follow-up and study are warranted.


Characteristics of HPRT-mutant T cell lines in a lupus patient treated with cyclophosphamide.
This report describes T cell lines derived from a patient with subacute cutaneous lupus after treatment with intravenous pulse cyclophosphamide. We selected for mitotically active, hypoxanthine-guanine phosphoribosyltransferase-deficient (HPRT-) T cells, by culture in a selective medium containing 6-thioguanine. When HPRT- cell lines were derived 6 days after pulse cyclophosphamide (CYC) treatment, they were predominantly CD8+ and T cell receptor (TCR) gamma/delta+, producing interferon-gamma (IFN gamma). Cell lines derived 21 days after CYC treatment were CD4+, TCR alpha/beta+ and produced both IFN gamma and interleukin-4. These results support a possible role for gamma/delta+ T cells in subacute cutaneous lupus and suggest a mechanism for the therapeutic effect of CYC.


Nutritional Quality of Hidden Food and Beverage Advertising Directed to Children: Extent and Nature of Product Placement in Mexican Television Programs.
(1) Background: Nutrient-poor, energy-dense food and beverage (F&B) advertisements influence children's food preferences, consumption, and purchase requests, contributing to overweight and obesity. Objective: To characterize the nutritional quality of F&B advertised by product placement (PP) in Mexican television programs with the highest audience ratings for children. (2) Methods: A total of 48 h of television programs between December 2016 and January 2017 during the hours with the highest ratings for children were analyzed. Nutritional quality was assessed through the Mexican Ministry of Health (MMH-NPM), the World Health Organization Regional Office for Europe (WHO-Europe), and the Pan American Health Organization nutrient profile models (PAHO-NPM). (3) Results: A total of 119 F&B were broadcast, of which more than 60% were unhealthy according to the three nutritional models. Reality shows and movies presented the most PP advertising. The food category most frequently advertised was sugar-sweetened beverages (41.2%). F&B advertised in children's programs had a higher content of energy, total fat, and saturated fat (p < 0.01). (4) Conclusion: The MMH-NPM was the most permissive and the PAHO-NPM was the strictest for evaluating nutritional quality. Mexico must strengthen the regulation of advertising to protect children from its negative effects on health.


Covert lie detection using keyboard dynamics.
Identifying the true identity of a subject in the absence of external verification criteria (documents, DNA, fingerprints, etc.) is an unresolved issue. Here, we report an experiment on the verification of fake identities, identified by means of their specific keystroke dynamics as analysed in their written response using a computer keyboard. Results indicate that keystroke analysis can distinguish liars from truth tellers with a high degree of accuracy - around 95% - thanks to the use of unexpected questions that efficiently facilitate the emergence of deception clues.


Spondylodiscitis associated with skin lesions caused by Rhizopus in a patient with systemic lupus erythematosus.
Mucormycosis is a serious and rare fungal disease caused by opportunistic fungi of the zygomycete class, order Mucorales. The main clinical presentations are rhinocerebral, pulmonary, cutaneous, gastrointestinal, and disseminated infections. There are few reports in the literature of spondylodiscitis caused by mucormycosis. We report a 53-year-old male patient presenting with subcutaneous nodules and severe low back pain radiating to the lower limbs. The patient had systemic lupus erythematosus (SLE) for 8 years and corticoid-induced diabetes. He had been using 60 mg/day of prednisone in the last year, with a recent pulse therapy regimen with methylprednisolone and cyclophosphamide to control the renal dysfunction. Nuclear magnetic resonance (NMR) of the spine showed spondylodiscitis. The patient underwent spinal arthrodesis and lesion biopsy. The histopathological study of the vertebra reported a necro suppurative inflammation with numerous fungal structures described as a wide range of hyaline hyphae. The histopathology of the cutaneous nodule exhibited an extensive suppurative lesion centered on the subcutaneous tissue, associated with a large amount of hyphae, similar to that found in the spinal lesion, suggestive of mucormycosis. The fungal culture showed the growth of Rhizopus spp. Treatment was performed with amphotericin B lipid complex 5 mg/kg/day for 60 days. After antifungal treatment, there was a progressive reduction in the number of subcutaneous nodules and total improvement of the patient's low back pain, with recovery of his gait. At the 18-month outpatient visit follow-up, the patient was stable and without recurrence. In our case, timely diagnosis enabled the removal of the osteoarticular focus and the targeted therapy resulted in a satisfactory clinical response, without sequelae or complications, despite the patient's underlying immunosuppressed status.


A multidimensional approach to pain assessment in critically ill infants during a painful procedure.
Inferring the pain level of a critically ill infant is complex. The ability to accurately extract the appropriate pain cues from observations is often jeopardized when heavy sedation and muscular blocking agents are administered. Near-infrared spectroscopy is a noninvasive method that may provide the bridge between behavioral observational indicators and cortical pain processing. We aimed to describe regional cerebral and systemic hemodynamic changes, as well as behavioral reactions in critically ill infants with congenital heart defects during chest-drain removal after cardiac surgery. Our sample included 20 critically ill infants with congenital heart defects, less than 12 months of age, admitted to the cardiac intensive care unit after surgery. Cerebral deoxygenated hemoglobin concentrations significantly differed across the epochs (i.e., baseline, tactile stimulus, noxious stimulus) (P=0.01). Physiological systemic responses and Face Leg Activity Cry Consolability (FLACC) pain scores differed significantly across the events (P<0.01). The 3 outcome measures were not found to be associated with each other. Mean FLACC pain scores during the painful procedure was 7/10 despite administration of morphine. Midazolam administration accounted for 36% of the variance in pain scores. We demonstrated with a multidimensional pain assessment approach that significant cerebral, physiological, and behavioral activity was present in response to a noxious procedure in critically ill infants despite the administration of analgesic treatment. Considering that the sedating agent significantly dampened pain behaviors, assessment of cerebral hemodynamic in the context of pain seems to be an important addition.


Dietary chromium methionine supplementation could alleviate immunosuppressive effects of heat stress in broiler chicks.
The present study was conducted to investigate the effects of dietary supplementation of chromium methionine (CrMet) on performance, immune responses, and stress status of broiler chicks subjected to heat-stress conditions. A total of 450 day-old Ross 308 broiler chicks were randomly distributed between 5 replicate pens (15 birds each) of 6 experimental treatments according to a 2 × 3 factorial arrangement of treatments including 2 temperature conditions (thermoneutral and heat stress) and 3 supplemental Cr levels (0, 500, and 1,000 μg/kg as CrMet). For induction of heat stress, the house temperature was set at 35 ± 2°C from 15 to 42 d of age. Results showed that the chicks subjected to heat-stress condition had lower (P < 0.01) feed intake, BW gain, and deteriorated (P < 0.05) feed conversion values compared with those kept in the thermoneutral house. Dietary supplementation with CrMet increased (P < 0.01) feed intake and improved (P < 0.01) weight gain and feed efficiency. There were significant Cr level × temperature interactions, so that inclusion of CrMet into the diets was more effective in heat-stressed chicks. Exposure to heat stress suppressed (P < 0.01) cutaneous hypersensivity response to phytohemagglutinin-P injection at 30 d of age, and dietary supplementation of 500 μg Cr/kg induced (P < 0.05) this response, with the greater impacts in heat-stressed chicks, resulting in a significant (P < 0.01) Cr × temperature interaction. Antibody responses against Newcastle and infectious bronchitis disease viruses were diminished (P < 0.01) in heat-stressed chicks. Dietary inclusion of CrMet improved (P < 0.05) antibody responses to different immunostimulants, and this effect was more pronounced in heat-stressed chicks. Exposure to heat stress caused a significant (P < 0.05) decrease in the proportion of helper (CD4+) T lymphocytes and increased cytotoxic (CD8+) T lymphocytes, resulting in a decreased (P < 0.01) CD4+ to CD8+ ratio in peripheral blood circulation. Supplementation of CrMet to heat-stressed chicks modulated (P < 0.01) plasma corticosterone level. The present findings indicate that dietary CrMet supplementation could alleviate heat-stress-induced growth retardation in broiler chicks. Moreover, supplemental CrMet modulated suppressive effects of heat stress on cellular and humoral immune responses.


Kinetics of degradation of diclofenac sodium in aqueous solution determined by a calorimetric method.
An isothermal heat conduction microcalorimeter has been used to study the stability of diclofenac sodium both alone and its inclusion complex with beta-cyclodextrin in aqueous solution. The rates of heat evolved during degradation of diclofenac sodium have been measured by a highly sensitive microcalorimetric technique as function of concentration, pH and temperature. The calorimetric accessible data have been incorporated in the equations for determination of rate constants, change in enthalpy and order of reaction. The decomposition of diclofenac sodium both alone and its inclusion complex with beta-cyclodextrin in solution corresponds to a pseudo-first order reaction. The values of rate constants, k's at 338.15 K, (calculated from the variation of heat evolution with the time) for the degradation of diclofenac sodium at pH 5, 6, 7, 8 and its inclusion complex with beta-cyclodextrin at pH 7 are found to be 4.71 x 10(-4), 5.69 x 10(-4), 6.12 x 10(-)4, 6.57 x 10(-4) and 4.26 x 10(-4) h(-1) respectively. There is good agreement between calorimetric determined t(0.5) and literature values. It has been found that beta-cyclodextrin retards the degradation of diclofenac sodium. The kinetic parameters have been calculated for the reaction. The negative entropy of activation suggests the formation of an ordered transition state.


Magnesium sulfate versus phenytoin for seizure prevention in amygdala-kindled rats.
Magnesium sulfate is widely used for seizure prophylaxis in preeclampsia-eclampsia. However, its anticonvulsant effects in other types of seizures have not been proved. Diphenylhydantoin has been widely characterized as the "gold standard" of anticonvulsants. In this study we compared the anticonvulsant effects of therapeutic blood levels of magnesium sulfate and phenytoin in seizures generated in amygdala-kindled rats. Eighteen male rats had a bipolar electrode stereotaxically implanted into the central nucleus of the amygdala. After recovery an electrical seizure threshold was determined for each rat. Rats were stimulated twice daily at their seizure thresholds (i.e., kindling) until three consecutive generalized tonic-clonic seizures occurred. Kindled rats randomly received one of the following intravenous injections in a volume of 1.5 ml/kg: saline solution, magnesium sulfate (30, 60, or 90 mg/kg), or phenytoin (12.5, 25, or 50 mg/kg). Fifteen minutes after injection rats were stimulated at their seizure thresholds, and electrical and behavioral seizure activity was assessed. Statistical comparisons were made by analysis of variance and post hoc comparisons when appropriate. Magnesium sulfate had no effect on any of the seizure parameters assessed. Phenytoin significantly reduced seizure duration (p < 0.01), duration of postictal depression (p < 0.01), and behavioral seizure stage (p < 0.01). Amygdala-kindled seizures are more potently inhibited by phenytoin than by magnesium sulfate.


Instruction-Based Approach-Avoidance Effects: Changing Stimulus Evaluation via the Mere Instruction to Approach or Avoid Stimuli.
Prior research suggests that repeatedly approaching or avoiding a certain stimulus changes the liking of this stimulus. We investigated whether these effects of approach and avoidance training occur also when participants do not perform these actions but are merely instructed about the stimulus-action contingencies. Stimulus evaluations were registered using both implicit (Implicit Association Test and evaluative priming) and explicit measures (valence ratings). Instruction-based approach-avoidance effects were observed for relatively neutral fictitious social groups (i.e., Niffites and Luupites), but not for clearly valenced well-known social groups (i.e., Blacks and Whites). We conclude that instructions to approach or avoid stimuli can provide sufficient bases for establishing both implicit and explicit evaluations of novel stimuli and discuss several possible reasons for why similar instruction-based approach-avoidance effects were not found for valenced well-known stimuli.


Validation of prescriber risk indicators obtained from prescription drug monitoring program data.
Prescription opioids are commonly overprescribed. However, validated measures of inappropriate controlled substance prescribing are lacking. This study examined associations between prescriber risk indicators developed as part of a public health surveillance project and medical board disciplinary actions against prescribers. We compiled 12 prescriber risk indicators using data from the Maine prescription drug monitoring program (PDMP) for 2010. We used logistic regression models to assess the relative likelihood of the top 1%, 2%, 5%, and 10% of prescribers on each risk indicator having been subject to medical board disciplinary actions, those citing inappropriate prescribing, or those involving license suspension or revocation, during 2010-2014, controlling for prescriber medical specialty and gender. The top 1% of prescribers for number of patients, opioid prescriptions per day, and opioid dosage prescribed per day had a greater likelihood of medical board disciplinary actions citing inappropriate prescribing, relative to a matched sample of other (non-top 1%) prescribers. Of the 56 prescribers in the top 1% for opioid prescriptions per day, nine (16.1%) were sanctioned for inappropriate prescribing, compared with 11 of 224 (0.5%) in the comparison group. The top 2% of prescribers for opioid dosage per day, and average distance patients travel to prescriber, had a greater likelihood of actions involving license suspension, revocation, or denial for renewal. Measures derived from PDMP data may be useful in assessing levels of inappropriate prescribing of controlled substances in a population of prescribers, and in evaluating changes associated with efforts to influence prescriber behavior.


Terahertz modulation induced by filament interaction.
We experimentally demonstrated that nonlinear filament interaction could spectrally modulate terahertz (THz) radiation generated from asymmetric two-color filaments. It was the spatial plasma density modulation in plasma channels that induced the THz spectral modulation. As a result of optical manipulation of electron density in the filamentary plasma gratings, the proportion of high-frequency THz spectra increased, while that of low-frequency THz spectra decreased, indicating that the increase of free electron density in the filamentary plasma grating brought about THz frequency upshifts.


Rapid single nucleotide polymorphism mapping in C. elegans.
In C. elegans, single nucleotide polymorphisms (SNPs) can function as silent genetic markers, with applications ranging from classical two- and three-factor mapping to measuring recombination across whole chromosomes. Here, we describe a set of 48 primer pairs that flank SNPs evenly spaced across the C. elegans genome and that work under identical PCR conditions. Each SNP in this set alters a DraI site, enabling rapid and parallel scoring. We describe a procedure using these reagents to quickly and reliably map mutations. We show that these techniques correctly map a known gene, dpy-5. We then use these techniques to map mutations in an uncharacterized strain, and show that its behavioral phenotype can be simultaneously mapped to three loci. Together, the reagents and methods described represent a significant advance in the accurate, rapid and inexpensive mapping of genes in C. elegans.


Biological dosimetry assessments of a serious radiation accident in Bulgaria in 2011.
In 2011, a serious radiation accident occurred in Stamboliyski, Bulgaria, in an industrial sterilisation facility using very-high-activity (60)Co sources. For the five persons accidentally exposed, biological dosimetry based on dicentric analysis was performed in Sofia and in Paris, where the patients were transferred for treatment. Before completing the chromosomal dose assessment, and for the most exposed person, a preliminary cytogenetic evaluation based on electronically transmitted metaphase images was made. The averaged acute whole-body dose estimates for the five patients ranged from 5.2 to 1.2 Gy, and good agreement was obtained between the two laboratories. The patients were also assessed by their prodromal responses and depressed blood cell counts over the first week. The cytogenetic dose estimates were in good accord with those derived from the blood counts, and both techniques indicated that, for the two most seriously exposed persons both techniques indicated that the initial prodromal reactions had suggested somewhat less severe exposure.


Nutritional habits of Flemish adolescent sprint athletes.
To investigate dietary habits of Flemish adolescent track and field athletes using a 7-d weighed-food record. Besides adequacy for growth, development, and physical performance, dietary health aspects were considered. Twenty-nine girls and 31 boys, with minimum 2 yr of track and field training practice, were recruited. All participants had daily breakfast (girls 22.5% +/- 5.5% of total energy intake [TEI]; boys 19.8% +/- 7.3%). Fruit in girls and juices and sports drinks in boys were consumed mostly between meals (girls 21.3% +/- 8.1% of TEI; boys 24.3% +/- 10.1%). Soft drinks contributed considerably to energy intake between meals in both sexes. Protein intake (1.5 +/- 0.3 g . kg-1 . d-1 for both sexes) was within the recommended daily intake (RDI) for strength athletes. Mean daily carbohydrate intake in girls was lower than in boys (girls 5.1 +/- 1.1 g/kg; boys 6.0 +/- 0.9 g/kg), with mono- and disaccharides contributing 26% to TEI in both sexes. Total fat intake was above 30% of TEI in more than half the participants, and only 10 participants had a saturated-fat intake below 10% of TEI. Fiber intake (girls 23.7 +/- 7.9 g; boys 29.1 +/- 11.2 g) was far below the Belgian RDI. Intake of vitamins and minerals were generally low, despite micronutrient supplementation in 37.5% of the participants. Few athletes reached all nutrient RDIs. Unhealthy food habits with regard to refined sugars, fat, and micronutrients were observed. These adolescent sprinters should be encouraged to consume more nonsweetened beverages, fruits, and vegetables.


Survival induced by short-scale autocorrelations in birth-death-diffusion models with negative growth.
In a birth, death, and diffusion process, the extinction-survival transition occurs when the average net growth rate is zero. For instance, in the presence of normally distributed time-varying stochastic growth rates with no autocorrelation, the transition indeed occurs at zero net growth rates. In contrast, if the growth rates are constant in time, a large enough variance in the growth rate will systematically ensure the survival of the global population even in a small system and, more importantly, even with a negative net growth rate. We here show that, surprisingly, for any intermediate temporal autocorrelation, any length of correlation, and any negative average growth rate, the same result holds. We test this argument on exponential and power law autocorrelation models and propose a simple condition for the growth rate variance at the transition.


Common Consequences of Uncommon Congenital Heart Disease: Exploring the Trilogy of Fallot With Infective Endocarditis and Cerebral Venous Thrombosis.
Trilogy of Fallot (ToF) is a rare congenital heart disease characterized by a combination of atrial septal defect, pulmonary stenosis, and right ventricular hypertrophy. It is more common in females and can cause symptoms such as cyanosis and breathlessness. ToF can lead to complications like thromboembolic events, including infective endocarditis (IE) and cerebral venous thrombosis (CVT). This case study discusses a nine-year-old female with ToF who also had IE and CVT. The patient recovered well following treatment with intravenous beta-lactam and aminoglycoside for IE and subcutaneous low-molecular-weight heparin for CVT.


Do food trichomes occur in Pinguicula (Lentibulariaceae) flowers?
Floral food bodies (including edible trichomes) are a form of floral reward for pollinators. This type of nutritive reward has been recorded in several angiosperm families: Annonaceae, Araceae, Calycanthaceae, Eupomatiaceae, Himantandraceae, Nymphaeaceae, Orchidaceae, Pandanaceae and Winteraceae. Although these bodies are very diverse in their structure, their cells contain food material: starch grains, protein bodies or lipid droplets. In Pinguicula flowers, there are numerous multicellular clavate trichomes. Previous authors have proposed that these trichomes in the Pinguicula flower play the role of 'futterhaare' ('feeding hairs') and are eaten by pollinators. The main aim of this study was to investigate whether the floral non-glandular trichomes of Pinguicula contain food reserves and thus are a reward for pollinators. The trichomes from the Pinguicula groups, which differ in their taxonomy (species from the subgenera: Temnoceras, Pinguicula and Isoloba) as well as the types of their pollinators (butterflies/flies and bees/hummingbirds), were examined. Thus, it was determined whether there are any connections between the occurrence of food trichomes and phylogeny position or pollination biology. Additionally, we determined the phylogenetic history of edible trichomes and pollinator evolution in the Pinguicula species. The species that were sampled were: Pinguicula moctezumae, P. esseriana, P. moranensis, P. emarginata, P. rectifolia, P. mesophytica, P. hemiepiphytica, P. agnata, P. albida, P. ibarrae, P. martinezii, P. filifolia, P. gigantea, P. lusitanica, P. alpina and P. vulgaris. Light microscopy, histochemistry, and scanning and transmission electron microscopy were used to address our aims with a phylogenetic perspective based on matK/trnK DNA sequences. No accumulation of protein bodies or lipid droplets was recorded in the floral non-glandular trichomes of any of the analysed species. Starch grains occurred in the cells of the trichomes of the bee-/fly-pollinated species: P. agnata, P. albida, P. ibarrae, P. martinezii, P. filifolia and P. gigantea, but not in P. alpina or P. vulgaris. Moreover, starch grains were not recorded in the cells of the trichomes of the Pinguicula species that have long spurs, which are pollinated by Lepidoptera (P. moctezumae, P. esseriana, P. moranensis, P. emarginata and P. rectifolia) or birds (P. mesophytica and P. hemiepihytica), or in species with a small and whitish corolla that self-pollinate (P. lusitanica). The results on the occurrence of edible trichomes and pollinator syndromes were mapped onto a phylogenetic reconstruction of the genus. Floral non-glandular trichomes play the role of edible trichomes in some Pinguicula species (P. agnata, P. albida, P. ibarrae, P. martinezii, P. filifolia and P. gigantea), which are mainly classified as bee-pollinated species that had originated from Central and South America. It seems that in the Pinguicula that are pollinated by other pollinator groups (Lepidoptera and hummingbirds), the non-glandular trichomes in the flowers play a role other than that of a floral reward for their pollinators. Edible trichomes are symplesiomorphic for the Pinguicula species, and thus do not support a monophyletic group such as a synapomorphy. Nevertheless, edible trichomes are derived and are possibly a specialization for fly and bee pollinators by acting as a food reward for these visitors.


The rate of source memory decline across the adult life span.
Previous studies have suggested that the ability to remember contextual information related to specific episodic experiences declines with advancing age; however, the exact moment in the adult life span when this deficit begins is still controversial. Source memory for spatial information was tested in a life span sample of 1,500 adults between the ages of 21 and 80. Initially, images of common objects were randomly presented on one quadrant of a screen while the participants judged whether they were natural or artificial. During the retrieval phase, these same images were mixed with new ones, and all images were displayed in the center of the screen. The participants were asked to judge whether each image was new or old, and whether it was old, to indicate in which quadrant of the screen it had originally been presented. Source accuracy decreased linearly with advancing age at a rate of 0.6% per year across all decades even after controlling for educational level; this decline was unaffected by sex. These results reveal that either spatial information becomes less efficiently bound to episodic representations over time or that the ability to retrieve this information decreases gradually throughout the adult life span.


[Imaging of intestinal obstructions].
The diagnosis of intestinal obstruction still rests on radiography of the abdomen without preparation. Three X-ray films must systematically be taken: a general film and a film centred on the diaphragmatic domes with the subject standing; another general film with the subject lying on his back. It is relatively easy to identify the obstructed segment, but the cause of obstruction remains difficult to determine. For small bowel obstruction, emergency surgery is often necessary. If the patient's condition permits, it may be useful to opacify the dilated segment in order to study the nature of the obstacle. Colonic obstruction is opacified through the anus, this route being more informative. There are two types of acute obstruction: by occlusion and by strangulation. The various causes are considered, but there are also incomplete obstructions and dilatations without obstruction.


Home again: effects of the Mother-Child Home Program on mother and child.
4 successive cohorts of low-income families were randomly assigned either to a home-based intervention program that focused on modeling verbal interaction between mother and child around selected toys and books or to comparison treatments. Large program effects were found on maternal interaction styles in videotaped observations. Small IQ and program-specific effects were found for children in contrast to much larger IQ effects found in earlier research. IQ effects did not appear to have been mediated by changes in maternal behavior. A variation in which toys and books were supplied without home visits was as effective as the full program on IQ but not on maternal behavior. 3 years postprogram , there were no detectable effects in achievement or IQ tests or in first grade teachers' ratings of school adjustment and performance, but IQ and achievement scores were near national norms. Reasons for discrepancies with earlier results are discussed. The results highlight the need for continued experimental evaluation of early intervention programs with safeguards to insure that samples are educationally at risk.


[Clinical application of magnifying colonoscopy in diagnosis and treatment of colorectal benign neoplastic lesions].
To evaluate the clinical value of magnifying endoscopy in diagnosis and treatment of colorectal benign neoplastic lesions. Seventy-eight colorectal lesions in 61 patients were examined with magnifying colonoscopy after indigo carmine dyeingìand pit pattern diagnosis was made for every lesion according to Kudos classification to differentiate neoplastic lesions from non-neoplastic lesions. The lesions were resected by endoscopic polypectomy and mucosectomy or surgical treatment. The diagnoses made by magnifying colonoscopy were compared with pathologic results. The diagnostic sensitivity of magnifying endoscopy for neoplastic lesions was 98.4% and specificity was 85.7%. The overall accuracy for adenoma and early colorectal cancer was 96.2%. 89.7% of adenomatous lesions were treated by endoscopic resection. The magnifying colonoscopy can provide instantaneous and accurate diagnosis of neoplastic lesions in colon and rectum,as well as minimally invasive treatment.


Suicide booths and assistance without moral expression: a response to Braun.
In a recent paper, Braun argued for an autonomy-based approach to assisted suicide as a way to avoid the expressivist objection to assisted dying laws. In this paper, I will argue that an autonomy-based approach actually extends the expressivist objection to assisted dying because it is not possible for one agent to assist another in pursuit of a goal without expressing that it would be good for that goal to come about. Braun argued that assisted dying should be viewed purely as an individual's autonomous action, but this requires the assistance of the medical professional to be understood as that of a non-moral automaton, such as a suicide booth. Instead, it will be argued that a beneficent motivation to promote human flourishing provides moral reasons for both non-interference in the actions, for example, suicide, of competent agents and for considering whether assisting another agent with their goal will promote their flourishing.


Increased intramyocellular lipid/impaired insulin sensitivity is associated with altered lipid metabolic genes in muscle of high responders to a high-fat diet.
The accumulation of intramyocellular lipid (IMCL) is recognized as an important determinant of insulin resistance, and is increased by a high-fat diet (HFD). However, the effects of HFD on IMCL and insulin sensitivity are highly variable. The aim of this study was to identify the genes in muscle that are related to this inter-individual variation. Fifty healthy men were recruited for this study. Before and after HFD for 3 days, IMCL levels in the tibialis anterior were measured by (1)H magnetic resonance spectroscopy, and peripheral insulin sensitivity was evaluated by glucose infusion rate (GIR) during the euglycemic-hyperinsulinemic clamp. Subjects who showed a large increase in IMCL and a large decrease in GIR by HFD were classified as high responders (HRs), and subjects who showed a small increase in IMCL and a small decrease in GIR were classified as low responders (LRs). In five subjects from each group, the gene expression profile of the vastus lateralis muscle was analyzed by DNA microarray analysis. Before HFD, gene expression profiles related to lipid metabolism were comparable between the two groups. Gene Set Enrichment Analysis demonstrated that five gene sets related to lipid metabolism were upregulated by HFD in the HR group but not in the LR group. Changes in gene expression patterns were confirmed by qRT-PCR using more samples (LR, n = 9; HR, n = 11). These results suggest that IMCL accumulation/impaired insulin sensitivity after HFD is closely associated with changes in the expression of genes related to lipid metabolism in muscle.


Inclusion of the Symbol Digit Modalities Test in a revised assessment of 'no evidence of disease activity-4 (NEDA-4)' in Latin-American patients with multiple sclerosis.
In relapsing-remitting multiple sclerosis (RRMS), no evidence of disease activity-3 (NEDA-3) is defined as the absence of: (1) relapses; (2) disability progression; (3) MRI activity (new/enlarged T2 lesions and/or gadolinium-enhanced T1 lesions). NEDA-4 status is defined as meeting all NEDA-3 criteria plus having an annualized percentage brain volume change (a-PBVC) >-0.4%. In individual patients, brain volume assessment is confounded with normal aging, methodological limitations and fluid-shift related fluctuations in brain volume. Cognitive impairment has been proposed as another component that should be integrated into therapeutic algorithms for RRMS. We aim to determine the proportion of patients failing to meet NEDA-4 criteria and to appraise whether the Symbol Digit Modalities Test (SDMT) is capable of replacing a-PBVC as one of the components of NEDA-4. We hypothesize that NEDA-4 has the potential to capture the impact of DMT therapies in RRMS. Forty-five patients were prospectively followed 1 and 2 years after their baseline assessment at the University of Chile Hospital. SIENA software was used to assess a-PBVC. At baseline, the patients had a mean age of 33.0 years (range 18-57), disease duration of 1.9 years (0.4-4), Expanded Disability Status Scale score of 1.3 (0-4), and 67% were female. The majority had RRMS (91% while 9% had clinically isolated syndrome (CIS)). Seventy-three percent were on the so-called first line DMTs such as interferons (53%), glatiramer acetate (13%), teriflunomide (9%), and 18% were on fingolimod. There was a serial decline in the proportion of NEDA: after 1 and 2 years of follow-up 60% and 47% met NEDA-3 status, and 38% and 27% met NEDA-4, respectively. At the last follow-up 21% remained on interferons, 47% were now on fingolimod, 4% on alemtuzumab and 2% on natalizumab. At year 1 and year 2, with the replacement of a-PBVC by SDMT, 53% and 40% of patients achieved a putative NEDA-4 status, respectively. Brain volumetric MRI has yet to be translated into clinical practice and SDMT may qualify as the fourth component of NEDA-4 definition. NEDA-4 has the potential to capture the impact of DMT therapies in RRMS earlier in the disease course of RRMS.


Brain evolution in social insects: advocating for the comparative approach.
Sociality is classified as one of the major transitions in the evolution of complexity and much effort has been dedicated to understanding what traits predispose lineages to sociality. Conversely, studies addressing the role of sociality in brain evolution (e.g., the social brain hypothesis) have not focused on particular traits and instead relied largely on measurements of relative brain composition. Hymenoptera range from solitary to advanced social species, providing enticing comparisons for studying sociality and neural trait evolution. Here we argue that measuring the role of sociality in brain evolution will benefit from attending to recent advances in neuroethology and adopting existing phylogenetic comparative methods employed in analysis of non-neural traits. Such analyses should rely on traits we expect to vary at the taxonomic level used in comparative analyses and include phylogenetic structure. We outline the limits of brain size and volumetric interpretation and advocate closer attention to trait stability and plasticity at different levels of organization. We propose neural traits measured at the cellular, circuit, and molecular levels will serve as more robust variables for evolutionary analyses. We include examples of particular traits and specific clades that are well-suited to answer questions about the role of sociality in nervous system evolution.


[Emergency cholecystectomy versus percutaneous transhepatic gallbladder drainage followed by delayed cholecystectomy in patients with moderate acute cholecystitis].
Objective: To analysis the curative effect of emergency cholecystectomy (EC) and percutaneous transhepatic gallbladder drainage (PTGBD) followed by delayed cholecystectomy (DC) on the patients with moderate acute cholecystitis. Methods: The perioperative dataof patients in EC group (n=47) and in PTGBD-DC group (n=49) were compared retrospectively. Results: Compared to PTGBD+ DC group, EC patients had a significantly more postoperative abdominal drainage time [(9.0±12.9) vs (3.4±2.1) days, P=0.041], more postoperative hospital stay after cholecystectomy [(8.2±3.2) vs (5.1±1.8) days, P=0.004], more intraoperative bleeding [(101±125) vs (33±37) ml, P=0.003], more patients of LC conversion to open cholecystectomy (OC) (19.1% vs 4.1%, P=0.021) and more patients of OC(14.9% vs 0, P=0.005). Also, there were higher incidence of respiratory failure(14.8% vs 2.0%, P=0.029), and admission for ICU(21.3% vs 2.0 %, P=0.003). Also, patients of total OC in non-biliary surgeons group were more than that of biliary surgeons group statistically(63.2% vs 14.3 %, P=0.001). Conclusion: PTGBD followed by DC in the treatment of moderate acute cholecystitis was better than EC, especially in patients with complicated comorbidities and in non-biliary surgeons.


Improving propensity score estimators' robustness to model misspecification using super learner.
The consistency of propensity score (PS) estimators relies on correct specification of the PS model. The PS is frequently estimated using main-effects logistic regression. However, the underlying model assumptions may not hold. Machine learning methods provide an alternative nonparametric approach to PS estimation. In this simulation study, we evaluated the benefit of using Super Learner (SL) for PS estimation. We created 1,000 simulated data sets (n = 500) under 4 different scenarios characterized by various degrees of deviance from the usual main-term logistic regression model for the true PS. We estimated the average treatment effect using PS matching and inverse probability of treatment weighting. The estimators' performance was evaluated in terms of PS prediction accuracy, covariate balance achieved, bias, standard error, coverage, and mean squared error. All methods exhibited adequate overall balancing properties, but in the case of model misspecification, SL performed better for highly unbalanced variables. The SL-based estimators were associated with the smallest bias in cases of severe model misspecification. Our results suggest that use of SL to estimate the PS can improve covariate balance and reduce bias in a meaningful manner in cases of serious model misspecification for treatment assignment.


Detection and automatic repair of nucleotide base-pair mutations by coherent light.
We show that phase-coherent optical techniques allow for the detection and automatic repair of mutations in nucleotide pairs. We demonstrate computationally that there is a laser pulse sequence that can detect the occurrence of a mutation caused by a double proton transfer between hydrogen-bonded nucleotide pairs and automatically repair it by converting the mutated nucleotide pair to the nonmutated one. The specific system chosen for this demonstration is the hydrogen-bonded 2-pyridone.2-hydroxypyridine dimer at typical internucleotide distances, a well-established model for tautomeric acid base pairs.


[Positron emission tomography with fluordesoxyglucose-F18 in follow-up of endometrial cancer].
To assess the utility of FDG-PET in the follow-up of patients treated for endometrial cancer and with suspicion of recurrence according to conventional imaging methods (CT, MRI) and/or elevation of serum tumour markers. Between April 2002 and December 2005, eleven patients underwent 17 FDG-PET studies (six with 2 studies); mean age was 63.4 yrs (range, 52-69 yrs) and time since diagnosis ranged from 11 months to 12 yrs (mean of 56 months). Initially, seven patients were in stage I, three in stage III and one in stage IV (FIGO classification). Histologically, they corresponded to 8 endometrioid carcinomas and 3 non endometrioid carcinomas. FDG-PET showed infradiaphragmatic uptake in 3 patients and disseminated disease in 7 cases. FDG-PET showed no uptake in one patient. CT (n = 7) or MRI (n = 7) detected infradiaphragmatic lesions in 5 patients and visceral lesions in 2. In 11 patients, tumour markers were elevated (CA125, n = 9; CA19.9, n = 2; CA15.3, n = 2). In 7 patients, FDG-PET modified the information yielded by conventional imaging techniques and in 4 patients, the FDG-PET contributed no additional information. In 2 patients, histologic confirmation of the lesions was obtained and in 9 patients, there were clinical follow-up (from 3 to 20 months, mean of 8.7 months) and imaging studies. FDG-PET is superior to CT and MRI for detecting recurrences in the follow-up of patients with endometrial cancer.


Acoustic changes in the speech of children with cerebral palsy following an intensive program of dysarthria therapy.
The speech intelligibility of children with dysarthria and cerebral palsy has been observed to increase following therapy focusing on respiration and phonation. To determine if speech intelligibility change following intervention is associated with change in acoustic measures of voice. We recorded 16 young people with cerebral palsy and dysarthria (nine girls; mean age 14 years, SD = 2; nine spastic type, two dyskinetic, four mixed; one Worster-Drought) producing speech in two conditions (single words, connected speech) twice before and twice after therapy focusing on respiration, phonation and rate. In both single-word and connected speech we measured vocal intensity (root mean square-RMS), period-to-period variability (Shimmer APQ, Jitter RAP and PPQ) and harmonics-to-noise ratio (HNR). In connected speech we also measured mean fundamental frequency, utterance duration in seconds and speech and articulation rate (syllables/s with and without pauses respectively). All acoustic measures were made using Praat. Intelligibility was calculated in previous research. In single words statistically significant but very small reductions were observed in period-to-period variability following therapy: Shimmer APQ -0.15 (95% CI = -0.21 to -0.09); Jitter RAP -0.08 (95% CI = -0.14 to -0.01); Jitter PPQ -0.08 (95% CI = -0.15 to -0.01). No changes in period-to-period perturbation across phrases in connected speech were detected. However, changes in connected speech were observed in phrase length, rate and intensity. Following therapy, mean utterance duration increased by 1.11 s (95% CI = 0.37-1.86) when measured with pauses and by 1.13 s (95% CI = 0.40-1.85) when measured without pauses. Articulation rate increased by 0.07 syllables/s (95% CI = 0.02-0.13); speech rate increased by 0.06 syllables/s (95% CI = < 0.01-0.12); and intensity increased by 0.03 Pascals (95% CI = 0.02-0.04). There was a gradual reduction in mean fundamental frequency across all time points (-11.85 Hz, 95% CI = -19.84 to -3.86). Only increases in the intensity of single words (0.37 Pascals, 95% CI = 0.10-0.65) and reductions in fundamental frequency (-0.11 Hz, 95% CI = -0.21 to -0.02) in connected speech were associated with gains in intelligibility. Mean reductions in impairment in vocal function following therapy observed were small and most are unlikely to be clinically significant. Changes in vocal control did not explain improved intelligibility.


Successful Revascularization of Infrapopliteal Chronic Total Occlusions Using the Plantar Arch as a Conduit and Retrograde Pedal Access.
Background: With the rising prevalence of critical limb ischemia (CLI), the pedal-plantar loop technique and retrograde access may be needed to increase interventional success. Case Report: A 63-year-old female with severe peripheral artery disease presented with a 2-month nonhealing wound on the dorsum of her left foot despite wound care. We inserted a 65-cm Destination Guiding Sheath and crossed the right superficial femoral artery (SFA) chronic total occlusion (CTO) that we initially treated with a 4.0-mm Ultraverse balloon. We attempted unsuccessfully to cross the distal anterior tibial artery into the dorsalis pedis artery. We obtained antegrade access of the posterior tibial artery at the level of the ankle with a 2.9-French Cook pedal access kit. We inserted a 90-cm CXI catheter with a 0.014 Fielder XT wire and used the lateral plantar artery as a conduit to cross the dorsalis pedis artery and distal anterior tibial artery CTO with retrograde wire manipulation via lateral plantar artery. Finally, we performed distal anterior tibial and dorsalis pedis CTO balloon angioplasty with a 2.5 × 220-mm Ultraverse balloon and performed SFA percutaneous transluminal angioplasty and stenting with a 7.0 × 120-mm Zilver PTX stent, postdilated with a 6.0-mm Ultraverse balloon. We successfully established in-line flow to the foot with 3-vessel runoff. The patient's wound healed in a month. Conclusion: Retrograde pedal access can improve the success rate of recanalization of below-the-knee disease in patients with CLI.


Growth, cell division, and fragmentation in a species of Flexibacter.
Flexibacter FS-1, a gram-negative gliding bacterium was grown in liquid culture as long (over 100-mum) filaments. The filaments possessed a triple-track wall which resembled that found in other gram-negative bacteria. Although phase-contrast microscopy indicated that the long filaments were nonseptate, electron microscopy revealed three or four septa along the length of each filament. The septa contained lysozyme-sensitive, electron-opaque material, presumed to be peptidoglycan, sandwiched between cell membranes. The outer triple track wall was not part of the septum. Mesosomes were seen in various areas of the cell and frequently were observed attached to septa in different stages of completion. Studies of the organism in slide culture revealed that individual filaments grew in an exponential fashion and divided in the middle despite the long length and multiseptate condition. When the temperature of a liquid culture growing exponentially with a generation time of 90 minutes was shifted from 30 to 35 C, the filaments fragmented into three or four shorter cells within 120 min. The short cells continued to grow exponentially at 35 C at approximately the same rate as at 30 C. When the culture was shifted back to 30 C, the cells immediately stopped dividing and began to elongate. After a period of 2 to 3 hr, cell division resumed. It is suggested that the shift-up in temperature induced the completion of the cross wall (centripetal growth of the triple-track wall) and cell separation at the sites of previously formed septa, whereas the shift-down in temperature caused a transient inhibition of cross-wall formation but not of growth. Fragmentation was inhibited by sodium azide but took place despite the inhibition of protein synthesis by chloramphenicol or the inhibition of deoxyribonucleic acid synthesis by mitomycin C.


The activation of P2Y2 receptors increases MCF-7 breast cancer cells migration through the MEK-ERK1/2 signalling pathway.
Adenosine 5'-triphosphate (ATP) is found in high concentrations in the extracellular microenvironment of tumours and is postulated to play critical roles in cancer progression. In the present study, we found that stimulation of human MCF-7 breast cancer cells with 30 µM ATP increased their migration by 140 ± 31%, whereas it had minor or no effect on their proliferation. This effect was prevented by the ectonucleotidase apyrase and was antagonized by suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, consistently with the participation of P2 receptors. MCF-7 cells expressed messenger RNA for all known P2Y receptors and for P2X2, P2X4, P2X5, P2X6 and P2X7 receptors. Brief applications (20 s) of external ATP resulted in a 50 pA P2X-like inward current. ATP, but not adenosine diphosphate or uridine diphosphate, increased the intracellular calcium concentration in absence of extracellular calcium, and this effect was prevented by the inhibition of phospholipase C. Uridine triphosphate (UTP) (10 µM) and 2-thio-UTP (10 µM) increased intracellular calcium concentration and cell migration to the same extent as ATP. The UTP-dependent increase in cell migration was absent in cells knocked-down for P2Y2. It was inhibited by MEK inhibitor PD98059. UTP induced a time-dependent phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), which was prevented by the incubation with PD98059. Taken together, these results highlight the importance of the purinergic signalling in cancer cells and indicate that the activation of P2Y2 receptors enhances breast cancer cells migration through the activation of a MEK-ERK1/2-dependent signalling pathway.


Expression of cupular dynamics while the macaque sleeps.
(1) The effect of brief periods of sleep on neural processing in the vestibulo-ocular reflex was studied in Macaca speciosa. (2) When sleep interrupted nystagmus during a modified Bárány spinning test, the time constant of mystagmus remained unchanged. (3) This finding shows that during light sleep the neural circuitry which generates a long nystagmus time constant from a short cupular time constant continues to function, even though nystagmus ceases.


Exenatide: a new option for the treatment of type 2 diabetes.
To evaluate available literature characterizing the pharmacology, pharmacokinetics, drug interactions, efficacy, and safety of exenatide in patients with type 2 diabetes. A PubMed database search (1966-May 2006) was conducted, using exenatide as the search term. The manufacturer's prescribing information was also used. English-language articles were selected and data were extracted with a focus on clinical outcomes associated with the treatment of patients with type 2 diabetes. Exenatide exerts a glucoregulatory effect by various mechanisms including secretion of glucose-dependent insulin, suppression of inappropriately high glucagon levels in patients with type 2 diabetes, delayed gastric emptying, and reduction of food intake. In placebo-controlled clinical studies, plasma exenatide concentrations appeared to exhibit dose-proportional kinetics, reaching peak plasma levels between 2 and 3 hours after a single subcutaneous injection. Exenatide's elimination half-life ranged from 3.3 to 4.0 hours, and the time to reach maximum concentration was about 2 hours. Interactions between exenatide and agents such as digoxin and lisinopril were not considered significant. In Phase III trials, exenatide demonstrated significant reduction of hemoglobin A1c levels from baseline and compared with placebo after 30 weeks of treatment in patients unable to achieve optimal glycemic control with metformin, a sulfonylurea, or oral combination therapy (0.4-0.9%). Patients' weight decreased with exenatide (0.9-2.8 kg), but adverse gastrointestinal (GI) events were common. Exenatide combined with thiazolidonediones, D-phenylalanine derivatives, meglitinides, or alpha glucosidase inhibitors has not been studied. Clinical trials have demonstrated that exenatide improves glycemic control when added to sulfonylureas and metformin, and it may be an alternative to insulin glargine in patients requiring additional therapy. Hypoglycemia has been encountered in clinical trials of exenatide, especially upon initiation of therapy with sulfonylureas (not with metformin); close patient monitoring is therefore recommended. Further studies should assess the impact of exenatide on clinical outcomes such as micro- and macrovascular disease.


Crystallization Retardation and Synergistic Trap Passivation in Perovskite Solar Cells Incorporated with Magnesium-Decorated Graphene Quantum Dots.
One of the encouraging strategies for enhancing the efficiency of perovskite solar cells (PSCs) is to reduce defects, trap states of pinholes, and charge recombination rate in the light absorber layer of perovskite, which can be addressed by increasing the perovskite grain size. The utilization of Mg-decorated graphene quantum dots (MGQD) or graphene quantum dots (GQDs) into a perovskite precursor solution for further crystal modification is introduced in this study. Studies on the crystalline structure and morphology of MGQD generated from GQDs demonstrate that MGQD has a greater crystal size than GQD. Therefore, higher light absorption in the whole UV-vis spectrum and a larger grain size for the perovskite/MGQD layer compared to the perovskite/GQD sample are achieved. Moreover, more photoluminescence peak quenching of perovskite/MGQD and extended carrier recombination lifetime (from 3 to 40 ns) verify the surface and grain boundary trap passivation compared to pristine perovskite. Consequently, PSCs in an n-i-p configuration containing perovskite/MGQD show a higher performance of 10.2% in comparison to the pristine perovskite at 7.2%, attributed to the enhanced JSC from 13.2 to 19.1 mA cm-2. Thus, incorporating MGQDs into the perovskite layer is a hopeful approach for obtaining a superior perovskite film with impressive charge extraction and decreased nonradiative charge recombination.


An improved ant colony optimization algorithm with fault tolerance for job scheduling in grid computing systems.
The Grid scheduler, schedules user jobs on the best available resource in terms of resource characteristics by optimizing job execution time. Resource failure in Grid is no longer an exception but a regular occurring event as resources are increasingly being used by the scientific community to solve computationally intensive problems which typically run for days or even months. It is therefore absolutely essential that these long-running applications are able to tolerate failures and avoid re-computations from scratch after resource failure has occurred, to satisfy the user's Quality of Service (QoS) requirement. Job Scheduling with Fault Tolerance in Grid Computing using Ant Colony Optimization is proposed to ensure that jobs are executed successfully even when resource failure has occurred. The technique employed in this paper, is the use of resource failure rate, as well as checkpoint-based roll back recovery strategy. Check-pointing aims at reducing the amount of work that is lost upon failure of the system by immediately saving the state of the system. A comparison of the proposed approach with an existing Ant Colony Optimization (ACO) algorithm is discussed. The experimental results of the implemented Fault Tolerance scheduling algorithm show that there is an improvement in the user's QoS requirement over the existing ACO algorithm, which has no fault tolerance integrated in it. The performance evaluation of the two algorithms was measured in terms of the three main scheduling performance metrics: makespan, throughput and average turnaround time.


Blood lymphocyte clonal excess in advanced non-Hodgkin's lymphoma. Relation to clinical data and prognosis.
Increasingly sensitive methods, based on the monoclonal nature of NHL, are used to detect tumour spread and remaining disease. Since the lymphomas are thought to arise due to successive genetic changes, clonal cells in different compartments do not necessarily represent the same disease despite a common clonal origin. In 179 patients with advanced NHL, clonal cells in peripheral blood were identified by light chain restriction analysed in flow cytometry, i.e. clonal excess (CE) analysis. CE was more common in low grade NHL (52%) than in high grade NHL (21%). In patients with a normal lymphocyte count CE was found in 23%. CE was significantly correlated to small cell histology and bone marrow involvement. In high grade NHL CE in peripheral blood was more common in those with discordant small or mixed cell involvement of the bone marrow. CE was significantly related to failure to achieve remission in both histologic subgroups. Survival was not influenced by CE in low grade NHL but in high grade NHL. In multivariate analyses however, CE did not emerge as an independent risk factor but age, B-symptoms and LDH were the major factors. The utility of blood CE analyses in clinical praxis has still to be settled and the prognostic value of CE per se seem limited in the current perspective. The existence of CE in high grade NHL might be a clue of different biology as compared to de novo high grade NHL.


One Year Follow-Up After Veriflex Phakic Intraocular Lenses Implantation for Correction of Myopia.
The aim of this study was to evaluate visual and refractive outcomes after Veriflex phakic intraocular lenses (pIOL) implantation in moderately myopic eyes as well as postoperative complications. This prospective clinical study included 40 eyes of 26 patients which underwent implantation of Veriflex for correction of myopia from -6.00 to -14.50 diopters (D) in the Eye Clinic Svjetlost Sarajevo, from January 2011 to January 2014. Uncorrected distance visual acuity (UDVA), manifest residual spherical equivalent (MRSE), intraocular pressure (IOP), endothelial cell (EC) density were evaluated at one, three, six and 12 months. Other complications in postoperative period were evaluated. For statistical analysis SPSS for Windows and Microsoft Excel were used. Out of 26 patients 14 had binocular and 12 monocular procedure, with mean age of 29.8±6.5 years. After 12 months mean UDVA was 0.73±0.20. Mean MRSE was -0.39±0.31D and 90% of eyes had MRSE within ±1D. EC loss was 7.18±4.33%. There was no significant change of IOP by the end of 12 months follow up period. The only intraoperative complication was hyphema and occurred in one eye. Few postoperative complications were: subclinical inflammation in three eyes (7,5%), pigment dispersion in four eyes (10%), ovalisation of papilla in 2 eyes (5%) and decentration of pIOL in 2 eyes (5%). Implantation of iris-claw phakic lenses Veriflex for treating moderately high myopia is a procedure with good visual and refractive results and few postoperative complications.


A saga of cancer epigenetics: linking epigenetics to alternative splicing.
The discovery of an increasing number of alternative splicing events in the human genome highlighted that ∼94% of genes generate alternatively spliced transcripts that may produce different protein isoforms with diverse functions. It is now well known that several diseases are a direct and indirect consequence of aberrant splicing events in humans. In addition to the conventional mode of alternative splicing regulation by 'cis' RNA-binding sites and 'trans' RNA-binding proteins, recent literature provides enormous evidence for epigenetic regulation of alternative splicing. The epigenetic modifications may regulate alternative splicing by either influencing the transcription elongation rate of RNA polymerase II or by recruiting a specific splicing regulator via different chromatin adaptors. The epigenetic alterations and aberrant alternative splicing are known to be associated with various diseases individually, but this review discusses/highlights the latest literature on the role of epigenetic alterations in the regulation of alternative splicing and thereby cancer progression. This review also points out the need for further studies to understand the interplay between epigenetic modifications and aberrant alternative splicing in cancer progression.


Metabolic syndrome and C-reactive protein in the general population: JMS Cohort Study.
In recent years some studies have shown that metabolic syndrome (MS) is associated with inflammation, indicated by high-sensitivity C-reactive protein (hsCRP), but there have been few population-based studies, especially in Japan. The study subjects were 2,191 men and women examined between 1992 and 1995 with the necessary data to ascertain MS as part of the Jichi Medical School Cohort Study. CRP was measured by nephelometry. There were 109 subjects defined as having MS (5.0%), and the proportion of MS cases was higher in men (9.4%) than in women (1.8%). Geometric mean and median CRP in the MS group was higher than that in the non-MS (geometric mean; p<0.001, median: 0.312 mg/L in MS and 0.122 mg/L). Proportion of MS increased with CRP, after the subjects were divided by tertile of CRP (odds ratio, 95% confidence interval 1st tertile as a reference; 2nd tertile: 2.9, 1.5-5.9, 3rd tertile: 5.7, 3.1-11.1). Inflammation, measured by the concentration of hsCRP, was elevated in cases of MS in the general Japanese population. Longitudinal data should be examined in the future.