Glycoproteomic study reveals altered plasma proteins associated with HIV elite suppressors.
HIV elite suppressors (ES) or controllers are individuals achieving control of viremia by their natural immunological mechanisms without highly active antiretroviral therapy (HAART). Study of the mechanisms responsible for the immunological suppression of viremia in ES may lead to the detection of individuals with ES and the effective control of HIV infection. We hypothesize that plasma glycoproteins play essential roles in the immune system of ES since plasma proteins are critical and highly relevant in anti-viral immunity and most plasma proteins are glycoproteins. To examine glycoproteins associated with ES, plasma samples from ES individuals (n=20), and from individuals on HAART (n=20), with AIDS (n=20), and no HIV infection (n=10) were analyzed by quantitative glycoproteomics. We found that a number of glycoproteins changed between ES versus HAART, AIDS and HIV- individuals. In sharp contrast, the level of plasma glycoproteins in the HAART cohort showed fewer changes compared with AIDS and HIV- individuals. These results showed that although both ES and HAART effectively suppress viremia, ES appeared to profoundly affect immunologically relevant glycoproteins in plasma as consequence of or support for anti-viral immunity. Bioinformatic analysis revealed that altered proteins in ES plasma were mainly associated with inflammation. This analysis suggests that overlapping, while distinguishable, glycoprotein profiles for inflammation and immune activation appeared to be present between ES and non-ES (HAART+AIDS) cohorts, indicating different triggers for inflammation and immune activation between natural and treatment-related viral suppression.


What's your story?
When you're in the midst of a major career change, telling stories about your professional self can inspire others' belief in your character and in your capacity to take a leap and land on your feet. It also can help you believe in yourself. A narrative thread will give meaning to your career history; it will assure you that, in moving on to something new, you are not discarding everything you've worked so hard to accomplish. Unfortunately, the authors explain in this article, most of us fail to use the power of storytelling in pursuit of our professional goals, or we do it badly. Tales of transition are especially challenging. Not knowing how to reconcile the built-in discontinuities in our work lives, we often relay just the facts. We present ourselves as safe--and dull and unremarkable. That's not a necessary compromise. A transition story has inherent dramatic appeal. The protagonist is you, of course, and what's at stake is your career. Perhaps you've come to an event or insight that represents a point of no return. It's this kind of break with the past that will force you to discover and reveal who you really are. Discontinuity and tension are part of the experience. If these elements are missing from your career story, the tale will fall flat. With all these twists and turns, how do you demonstrate stability and earn listeners' trust? By emphasizing continuity and causality--in other words, by showing that your past is related to the present and, from that trajectory, conveying that a solid future is in sight. If you can make your story of transition cohere, you will have gone far in convincing the listener--and reassuring yourself--that the change makes sense for you and is likely to bring success.


The Assessment of the Socioemotional Disorder in Neurodegenerative Diseases with the Revised Self-Monitoring Scale (RSMS).
Social cognition helps people to understand their own and others' behavior and to modulate the way of thinking and acting in different social situations. Rapid and accurate diagnoses of neurodegenerative diseases are essential, as social cognition is affected by these diseases. The Revised Self-Monitoring Scale (RSMS) is a scale that detects social-emotional cognition deficits. The aim of the current study is to examine how socioemotional parameters are affected by neurodegenerative diseases and whether the RSMS can discern these disorders based on the socioemotional parameters in the Greek population. A total of 331 dementia subjects were included. Mini Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination (Revised, ACE-R) measurements were used in order to assess the cognitive deficits. The Neuropsychiatric Inventory (NPI) was used for the evaluation of the neuropsychiatric symptoms. The RSMS and its two subscales was used in order to detect the socioemotional deficits. The RSMS and its two subscales (RSMS_EX and RSMS_SP) can effectively detect neurodegenerative diseases. The RSMS can detect bvFTD in Alzheimer's Disease (AD), AD in a healthy cohort, behavioral variant Frontotemporal Dementia (bvFTD) in a healthy cohort, bvFTD in Parkinson's Disease (PD) and Frontotemporal Semantic Dementia (FTD/SD) in a healthy cohort. It is a useful tool in order to detect frontotemporal dementias. RSMS correlated negatively with the NPI questionnaire total and the subcategories of apathy, disinhibition and eating disorders. The RSMS results are associated with the ACE-R score (specifically verbal fluency). The RSMS is a helpful tool in order to identify socioemotional deficits in neurodegenerative dementias. It is also a useful scale that can discern bvFTD and svPPA in AD patients. A worse RSMS score correlates with a worse ACE-R and NPI. It seems to be a useful scale that can reliably measure social behavior in non-reversible neurodegenerative disorders, such as AD, FTD (bvFTD, svPPA), PDD and PD. The results also apply to the Greek population.


Using humour as an extrinsic source of emotion regulation in young and older adults.
It has been suggested that intrinsic abilities for regulating emotions remain stable or improve with ageing, but, to date, no studies have examined age-related differences in extrinsic emotion regulation. Since humour has been found to be an effective form of emotion regulation, we used a paradigm similar to that of Strick and colleagues (2009) with two objectives: to compare extrinsic humorous emotion regulation in young and older adults and to test whether the potential beneficial effect of humour on negative emotion is better explained by the cognitive distraction hypothesis or by the positive affect elicitation hypothesis. To this end, neutral, moderately, and strongly negative pictures followed by humorous, simply positive, or weird cartoons, controlled for both their funniness and cognitive demands, were presented to 26 young and 25 older adults with the instruction to report their negative feelings. When induced to feel moderately negative emotions, both young and older adults reported a lower negative feeling after viewing the humorous cartoons than after the other ones. This indicates that the extrinsic humorous emotion regulation skill remains stable with ageing and suggests that the beneficial effect of humour on emotional feeling cannot be seen as a purely cognitive distraction.


Vogesella mureinivorans sp. nov., a peptidoglycan-degrading bacterium from lake water.
A novel, non-pigmented, rod-shaped, Gram-negative strain was isolated from mesotrophic lake water in Zealand, Denmark. Phylogenetic analysis of the 16S rRNA gene sequence of the bacterium, designated strain 389(T), indicated that the strain belonged to the genus Vogesella and formed a monophyletic group with Vogesella perlucida DS-28(T) (99.1 % nucleotide similarity); it was less related to Vogesella indigofera ATCC 19706(T) (96.9 % similarity) and Vogesella lacus LMG 24504(T) (96.8 % similarity). Hybridization of DNA from strain 389(T) and V. perlucida demonstrated a reassociation of 50.6 ± 9.6 %. The DNA G+C content of strain 389(T) was 61.2 mol%. The fatty acid profile of the strain differed from those of the other strains representing the genus Vogesella by a high content of C₁₆:₁ω7c and/or iso-C₁₅:₀ 2-OH (71.6 %) and a lower content of C₁₆: ₀. Strain 389(T) was capable of degrading peptidoglycan and had chitinase and lysozyme activities, possibly associated with the degradation of peptidoglycan, and had capacity for degradation of several other polymer compounds. Based on phenotypic and genotypic characteristics, strain 389(T) represents a novel species, for which we propose the name Vogesella mureinivorans sp. nov. The type strain is 389(T) (=DSM 21247(T) =LMG 25302(T)).


Intradermal, low dose, short course hepatitis B vaccination.
Seventy-five of 88 (85.2%) vaccinees seroconverted at three months after three 2 micrograms doses of a plasma-derived hepatitis B vaccine had been given intradermally one month apart. Vaccinees under 30 years of age had a significantly better seroconversion rate (88.8%) than older subjects (50%) as measured at three months. Forty-three of 47 (91%) vaccinees who were bled one year post vaccination had antibody levels in excess of 10 IU/1. This study indicates that short course, low dose, intradermal vaccination with plasma-derived hepatitis B vaccine may be a viable and cheap regimen for inducing immunity against hepatitis B in younger subjects.


[Seasonal and individual characteristics of the blood fibrinolytic system reaction to the physical load].
33 untrained test subjects (16 males and 17 females aged 18) have been studied for one year for their blood fibrinolysis reaction to a one-time 20-minute bicycle-ergometric large-capacity load (N male = 2.66 watt/kg, N female = 2.3 watt/kg). It is known that at rest the blood fibrinolytic activity (FA) has its seasonal characteristics: it is relatively high in the autumn and spring and low in the winter and summer. On the average, in the winter and in the summer physical activity stimulates the blood clot lysis whereas in the autumn and in the spring it does not. The direction and the intensity of the fibrinolysis system response to work have individual features: in the autumn and in the spring they are connected with its initial state (they increase when the blood FA is low and decrease when the blood FA is high) as well as they have large fluctuations, whereas in the winter and in the summer they are not subject to these laws. According to the parameters of the directional response to the load and its permanence there are three types of response: a) Hyperfibrinolytic, which is characterized by the FA increase when there is a physical load applied in all seasons of the year, having a low initial FA level at rest; b) Hypofibrinolytic, the representatives of which have a stable reaction of fibrinolysis oppression when there is a physical load applied, not depending on the season of the year and the initial level, having a high initial level of FA in the autumn and in the spring and low--in the winter and in the summer; c) Unstable, in which the direction of the fibrinolysis system response to the physical exercises is variable. The conclusion is that the development of thromboembolic complications as a consequence of having a physical load is most likely to be expected from those who have a hypofibrinolytic type of reaction while this is very unlikely to be expected from the representatives of the hyperfibrinolytic type.


Intratracheal transplantation of bone marrow-derived mesenchymal stem cells reduced airway inflammation and up-regulated CD4⁺CD25⁺ regulatory T cells in asthmatic mouse.
Mesenchymal stem cells attenuate the severity of lung injury due to their immunomodulatory properties. The effect of bone marrow-derived mesenchymal stem cells on asthma is seldom reported. We have examined the effect of BMSCs on airway inflammation in asthma. Forty female BALB/c mice were equally randomised into PBS group, BMSCs treatment group, BMSCs control group and asthmatic group. Reactivity of the airway to acetylcholine was measured by barometric plethysmography. Cytokine profiles of bronchoalveolar lavage fluid and serum were determined by enzyme-linked immunosorbent assay. Morphometric analysis was done with haematoxylin and periodic-acid Schiff staining. Engraftment of BMSCs in asthmatic mice significantly decreased the number of eosinophils and mononuclear cells in bronchoalveolar lavage fluid and the airway (P < 0.05). Both goblet cell hyperplasia and responsiveness to acetylcholine were significantly reduced in BMSCs treatment groups. Moreover, BMSCs engraftment caused significant increases the ratio of Treg in pulmonary lymph node and interleukin-10 (IL-10) and interleukin-12 levels in BALF and serum. We conclude that BMSCs engraftment ameliorated airway inflammation and improved lung function in asthmatic mouse and the protective effect might be mediated by upregulating Treg and partly involved with increasing IL-10.


Conjugated linoleic acid and betaine affect lipolysis in pig adipose tissue explants.
Consumers' demand of leaner meat products is a challenge. Although betaine and conjugated linoleic acid (CLA) have the potential to decrease porcine adipose tissue, their mode of action is poorly understood. The aim of the study was to determine the lipolytic effect of betaine and CLA in the adipose tissue of Iberian pigs. Adipose tissue explants from five pigs (38 kg BW) were prepared from dorsal subcutaneous adipose tissue samples and cultivated for 2 h (acute experiments) or 72 h (chronic experiments). Treatments included 100 µM linoleic acid (control), 100 µM trans-10, cis-12 CLA, 100 µM linoleic acid + 1 mM betaine and 100 µM trans-10, cis-12 CLA + 1 mM betaine (CLABET). To examine the ability of betaine or CLA to inhibit insulin's suppression of isoproterenol-stimulated lipolysis, test medium was amended with 1 µM isoproterenol ±10 nM insulin. Media glycerol was measured at the end of the incubations. Acute lipolysis (2 h) was increased by CLA and CLABET (85% to 121%; P < 0.05) under basal conditions. When lipolysis was stimulated with isoproterenol (1090%), acute exposure to betaine tended to increase (13%; P = 0.071), while CLA and CLABET increased (14% to 18%; P < 0.05) isoproterenol-stimulated lipolysis compared with control. When insulin was added to isoproterenol-stimulated explants, lipolytic rate was decreased by 50% (P < 0.001). However, supplementation of betaine to the insulin + isoproterenol-containing medium tended to increase (P = 0.07), while CLABET increased (45%; P < 0.05) lipolysis, partly counteracting insulin inhibition. When culture was extended for 72 h, CLA decreased lipolysis under basal conditions (18%; P < 0.05) with no effect of betaine and CLABET (P > 0.10). When lipolysis was stimulated by isoproterenol (125% increase in rate compared with basal), CLA and CLABET decreased glycerol release (27%; P < 0.001) compared with control (isoproterenol alone). When insulin was added to isoproterenol-stimulated explants, isoproterenol stimulation of lipolysis was completely blunted and neither betaine nor CLA altered the inhibitory effect of insulin on lipolysis. Isoproterenol, and especially isoproterenol + insulin, stimulated leptin secretion compared with basal conditions (68% and 464%, respectively; P < 0.001), with no effect of CLA or betaine (P > 0.10). CLA decreased leptin release (25%; P < 0.001) when insulin was present in the media, partially inhibiting insulin stimulation of leptin release. In conclusion, betaine and CLA produced a biphasic response regarding lipolysis so that glycerol release was increased in acute conditions, while CLA decreased glycerol release and betaine had no effect in chronic conditions. Furthermore, CLA and CLABET indirectly increased lipolysis by reducing insulin-mediated inhibition of lipolysis during acute conditions.


Model analysis of transcapillary exchange: the role of cyclotron produced isotopes in the study of the capillary permeability of substances.
The purpose of this paper is to review different models used in the interpretation of capillary permeability studies using tracer dilution methods, with special emphasis on the role of cyclotron-produced isotopes. The physical model is a simplified description of the biological system, and the mathematical formalism is a device by which the model and experimental data can be compared. If there is a correlation and the solution is unique and consistent, the model is considered acceptable. Capillaries--the end organs of the circulatory system--are physiologically important because they are the site for the exchange of materials (oxygen, glucose, waste products etc.). The positive and negative findings in radionuclide imaging studies are caused by changes in capillary permeability. The indicator diffusion methods have many advantages over the conventional compartmental analyses. The diffusion models take into account the normal histological structure of the tissue and it is possible to get information about both capillary and cellular physiology. Short-lived, cyclotron produced positron emitting radionuclides, carbon-11, nitrogen-13, oxygen-15 and fluorine-18, are suitable for the study of transcapillary exchange.


Construction of alpha-helix peptides with beta-cyclodextrin and dansyl units and their conformational and molecular sensing properties.
In order to apply de novo peptide design to molecular sensing, we designed and synthesized a-helical peptides with beta-cyclodextrin (beta-CDx) as a binding site and a dansyl unit (Dns) as a fluorescence sensing site. The conformational and molecular sensing properties of the peptides with beta-CDx and Dns in various positions were investigated. Circular dichroism and fluorescence measurements revealed that beta-CDx and Dns form intramolecular complexes which depend on their positions in the peptides. In the 17 residual peptides named EK3 and EK3R, in which beta-CDx and Dns were introduced at the fourth and the eighth positions (EK3) or at the eighth and the fourth positions (EK3R), Dns was deeply included in the CDx cavity and formed a more stable self-inclusion complex with CDx than in the peptides EK6 and EK6R, in which these moieties were at the eighth and the fifteenth positions or at the fifteenth and the eighth positions, respectively. The stability of the self-inclusion complex between beta-CDx and Dns controlled the a-helix structure as well as the binding and sensing abilities for the exogenous guests. These results demonstrate the usefulness of peptide tertiary structure for arranging CDx and other functional units, and suggest that this approach is important in the development of a new type of CDx-based sensory system.


The effect of trimethoprim/sulfamethoxazole on Friend erythroleukemia cells.
Cultures of Friend erythroleukemia cells were subjected to the antibiotics trimethoprim (T) and sulfamethoxazole (S) at levels equal to or below the usual therapeutic range. At T 8 microgram/ml and S 40 microgram/ml, cell growth was arrested, cells appeared megaloblastic, and the examination of cell-cycle distribution by flow microfluorimetry revealed arrest in S phase. With a tenfold reduction in drug levels (T, 08 microgram/ml; S, 4 microgram/ml) cell growth was less markedly inhibited, morphology remained megaloblastic, and S-phase block was still dramatic. A further tenfold reduction (T, 0.08 microgram/ml; S, 0.4 microgram/ml), well below effective antibacterial levels, allowed normal cell growth and morphology but DNA synthesis was still inhibited. Additions of folinic acid at 100 ng/ml averted all drug effects. Thus T/S can affect cell replication even at levels well below those usually employed and could prolong the rate of recovery of hematopoietic cells in the myelosuppressed patient.


[Clinical symptomatology and histopathological changes in Peyronie's disease: a comparative analysis].
Our understanding of the etiology of Peyronie's disease (IPP) as well as the diagnostic and therapeutic approach is suboptimal. In order to improve this situation, we conducted a comparative retrospective analysis between the clinical symptoms of 50 patients with IPP and their histopathological results after radical plaque excision. From 106 patients with IPP who consulted our clinic between 2002 and 2004, fifty were selected after clinical examination (sonography, Doppler sonography, DICC cavernosometry, X-ray) for surgery. The median age was 57.2 years. The plaque material was examined qualitatively and semi-quantitatively. Perivascular infiltrations and the type of the cells have been investigated immunhistochemically, and the structure of collagen was analysed by polarisation microscopy. In all 50 plaques, the tunica albuginea was fibrotic. In 41 cases the corpora cavernosa were infiltrated too. In 22 patients, the cavernosogram revealed venous leakage from the penile shaft. 32 plaques showed inflammatory infiltrations, 21 pathological vessels and 16 osseous metaplasia. In 13 plaques the fibrosis was stable and areactive. Mostly patients with metaplastic plaques or atypical vessels suffered from pain and erectile dysfunction. The results 6 months after plaque resection were best in painless patients who had that were plaques well marked off from the surrounding tissue (n = 13). Patients with aggressive fibroses of the corpora cavernosa (n = 5) and venous leakages from the penile shaft (n = 10) showed the worst results. A preoperative biopsy of IPP plaques could improve the quality of therapeutic decision. Painless patients with well marked and detectable plaques are suitable candidates for surgery. An operation is not the first-line option for patients with aggressive fibroses, venous leakages and painful indurations with fuzzy demarkation.


Consistent behavioural traits and behavioural syndromes in pairs of the false clown anemonefish Amphiprion ocellaris.
Using the social clown anemonefish Amphiprion ocellaris, whether individuals exhibited consistency in activity levels, boldness and sociability in a paired context, and whether these three behavioural traits were positively correlated within a single behavioural syndrome, was investigated. The results highlight that consistent individual differences in behaviour are expressed in a social fish and suggest that consistent behavioural traits and behavioural syndromes could influence the structure and functioning of their societies.


MSR1 variants and the risks of prostate cancer and benign prostatic hyperplasia: a population-based study in China.
Data from epidemiologic and twin studies suggest an important role of genetic susceptibility in prostate cancer. Variants of the macrophage scavenger receptor 1 (MSR1) gene have been linked to both hereditary and sporadic prostate cancer, although the evidence is inconclusive. Most studies have been conducted on Caucasians. The role of MSR1 in prostate cancer development among Asians, for whom rates of prostate cancer are low but rising rapidly, is unclear. To evaluate further the relationship between MSR1 variants and prostate cancer risk, we sequenced all the 11 MSR1 exons, exon-intron junctions, promoter regions, as well as 5' and 3' untranslated regions (UTRs) in 86 individuals from Shanghai, China. We identified a total of 21 sequence variants, including three novel variants that have not been reported previously. To balance genotyping cost and the capacity to capture sufficient genetic variation, we genotyped four haplotype-tagging variants (P275A, INDEL7, P346P and 3' UTR 70006), which capture 85% of the genetic variation in MSR1 in this population. These four variants, plus two other variants (PRO3 and INDEL1) that have been linked to prostate cancer risk in the previous studies, were typed for all study subjects, which included 130 prostate cancer cases, 130 patients with benign prostatic hyperplasia and 150 controls randomly selected from the population. Three of the six variants were associated with prostate cancer. Men with a P346P (a novel variant) G allele (AG + GG) had a significantly reduced risk of total prostate cancer [odds ratio = 0.47, 95% confidence interval (CI) 0.23-0.96], whereas those with a P275A G allele had a 37% reduced risk of prostate cancer (95% CI 0.39-1.02), with more pronounced reduction in risk seen for localized cancer cases (odds ratio = 0.25, 95% CI 0.12-0.52; P = 0.001). In addition, men with the INDEL7 variant had a 67% reduced risk of localized cancer (95% CI 0.16-0.68). Based on the four tagging variants, we inferred four major haplotypes that accounted for >90% of the haplotype variation in this population. The haplotype frequencies were significantly different between localized prostate cancer cases and controls, with a global P value of 0.004, and the haplotype containing the minor alleles of the P275A and INDEL7 variants was associated with a significantly reduced risk of localized prostate cancer (odds ratio = 0.28, 95% CI 0.13-0.59), relative to the most common haplotype. These results, although modest and confined mainly to localized prostate cancer, suggest that MSR1 polymorphisms may play a role in prostate cancer etiology in Chinese men. The role of MSR1 warrants further investigation in larger studies and other populations.


Percutaneous transrenal ureteral plug embolization: is there a need for tissue adhesives?
We aimed to evaluate the feasibility, effectiveness and safety of ureteral embolization exclusively using Amplatzer Vascular Plugs (AVPs) in the management of ureteral leakages. A retrospective analysis of 7 patients with ureteral leakages and fistulas having undergone transrenal ureteral embolization with AVPs was performed. In all cases, AVPs were deployed via a preexisting percutaneous transrenal nephrostomy tube. Technical and clinical success as well as complications were evaluated. During a 4-year study period, 11 ureters in 7 patients were embolized using AVPs. In one case additional coil embolization was conducted. Technical success in terms of sufficient occlusion of the treated ureter was achieved in 100% of the procedures. Median size of used plugs was 16.0 mm (range, 12-18 mm). Number of deployed AVPs ranged between one and three. Median procedural time was 24.00 minutes, and a median dose area product of 58.92 Gy•cm2 was documented. No procedure-related complications occurred. During a median follow-up period of 7 weeks, recurrence of the treated leak could not be observed. Ureteric plug embolization in patients with ureteral leakages or fistulas is a feasible, effective, and safe technique, even without the addition of tissue adhesives. However, due to the often limited prognosis and life expectancy of the affected patients, long-term experiences are still lacking.


Quantitation of polyphenols in different apple varieties.
Forty-one apple samples, representing eight of the most widely cultivated varieties in western Europe, were collected in Trentino, Italy. Samples were extracted from fresh fruit with a mixture of acetone/water to achieve a good extraction of polyphenols, including proanthocyanidin oligomers which were analyzed by normal-phase HPLC. Up to 20 compounds including catechin, epicatechin, B2 procyanidin, hydroxycinnamates, flavonols, anthocyanins, and dihydrochalcones were analyzed by reversed-phase HPLC and LC-MS. Total polyphenol content was independently measured with an optimized Folin-Ciocalteu assay. The mean content of total polyphenols lay between 66.2 and 211.9 mg/100 g of FW depending on the variety. With chromatographic analysis, it was possible to explain the whole amount of total polyphenols measured by the FC assay. Flavanols (catechin and proanthocyanidins) are the major class of apple polyphenols (71-90%), followed by hydroxycinnamates (4-18%), flavonols (1-11%), dihydrochalcones (2-6%), and in red apples anthocyanins (1-3%).


Intramolecular dimerization is required for the chlamydia-secreted protease CPAF to degrade host transcriptional factors.
We previously identified a chlamydial protein designated CPAF (chlamydia protease/proteasome-like activity factor) that is secreted into host cell cytosol for degrading host transcription factors required for major histocompatibility complex antigen expression. Here we report that CPAF, synthesized as a 70-kDa proprotein, is processed into two fragments (designated CPAFn and CPAFc) to form intramolecular dimers that are much more stable than the naïve CPAF. Precipitation with antibodies that recognized CPAF dimers removed the proteolytic activity responsible for degrading host transcription factor RFX5 from chlamydia-infected host cell cytosol, while precipitation with antibodies that recognized free CPAF fragments alone did not remove this activity. Separation of CPAFn from CPAFc resulted in a loss of proteolytic activity. Furthermore, neither expressed full-length CPAF that was not processed nor coexpressed CPAFn and CPAFc fragments that failed to form dimers degraded RFX5. These observations demonstrate that intramolecular dimerization is required for CPAF to degrade host transcription factors, a strategy that is utilized by an obligate intracellular bacterial species to evade host defenses.


Pedobacter kyonggii sp. nov., a psychrotolerant bacterium isolated from forest soil.
Strain K-4-11-1T, a psychrotolerant, light salmon-coloured, Gram-stain-negative, non-motile and rod-shaped bacterium, was isolated from forest soil of Kyonggi University, Suwon, South Korea. It was able to grow at 0-32 °C, at pH 5.0-10.0 and with 0-1.5 % (w/v) NaCl. This strain was taxonomically characterized by a polyphasic approach. Based on 16S rRNA gene sequence analysis, strain K-4-11-1T belongs to the genus Pedobacter and is closely related to Pedobacter ginsenosidimutans THG-45T (98.75 % sequence similarity), Pedobacter borealis G-1T (98.48 %), Pedobacter terrae DS-57T (98.20 %), Pedobacter agri PB92T (97.92 %) and Pedobacter suwonensis 15-52T (97.84 %). The only respiratory quinone was menaquinone-7. The major polar lipids were phosphatidylethanolamine and unidentified glycolipids. The predominant fatty acids of strain K-4-11-1T were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C15 : 0, iso-C17 : 0 3-OH, anteiso-C17 : 0 and summed feature 9 (iso-C17 : 1ω9c and/or C16 : 0 10-methyl). The genomic DNA G+C content of this novel strain was 38.3 mol%. The DNA-DNA relatedness values between strain K-4-11-1T and P. ginsenosidimutans KACC 14530T, P. borealis KACC 14287T, P. terrae KACC 13766T, P. agri KACC 13768T and P. suwonensis KACC 11317T were 40.0, 36.3, 37.0, 32.3 and 29.7 %, respectively. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished this novel strain from its closest phylogenetic neighbours. Thus, strain K-4-11-1T represents a novel species of the genus Pedobacter, for which the name Pedobacter kyonggii sp. nov. is proposed. The type strain is K-4-11-1T (=KEMB 9005-574T=KACC 19174T=JCM 31916T).


Fibroblast growth factor-2 has opposite effects on human breast cancer MCF-7 cell growth depending on the activation level of the mitogen-activated protein kinase pathway.
In human breast cancer MCF-7 and MCF-7ras cells, we demonstrated that whereas insulin had a mitogenic effect on both cell lines, fibroblast growth factor-2 (FGF-2) had opposite effects, stimulating MCF-7 and inhibiting MCF-7ras cell proliferation. The inhibitory signal induced by FGF-2 was related to sustained mitogen-activated protein kinase (MAPK) activation in MCF-7ras cells, while transient MAPK activation was associated with MCF-7 cell proliferation. FGF-2 was further used in combination with insulin or cAMP. In MCF-7 cells, insulin and cAMP reversed the mitogenic effect of FGF-2. In MCF-7ras cells, insulin did not modify the inhibitory effect of FGF-2, but cAMP markedly enhanced it. These effects were also associated with an increased level and duration of MAPK activation. PD98056 abolished the effect of FGF-2 on DNA synthesis in both cell lines, demonstrating that the dual effect of FGF-2 on cell proliferation is dependent on the activity of the extracellular-signal-regulated kinase 1 and 2 (ERK1/2) signalling pathway.


In vitro cell culture of patient derived malignant pleural and peritoneal effusions for personalised drug screening.
Malignant serous effusion (MSE) denotes a manifestation of metastatic disease with typical high concentrations of both cancer and immune cells, making them an ideal resource for in vitro cytologic studies. Hence, the aim of the study was to investigate the features of 2D and 3D MSE culture systems as well as their feasibilities for in vitro drug screening. Pleural and peritoneal effusions from 8 patients were collected and processed for 2D monolayer and 3D hanging drop cell culture into GravityPLUS™ plates. Representative markers for cell components, proliferation rate and tumour classification were investigated by immunohistochemistry, followed by absolute quantification using a digitalised image analysis approach. Further, we implemented another 3D cell culture model based on a low attachment method for in vitro drug sensitivity testing of carboplatin, pemetrexed and pembrolizumab for 5 patients. Monolayer cell culture was favourable for the growth of mesothelial cells, while hanging drop culture in GravityPLUS™ plates showed better ability for preserving cancer cells, inducing positive diagnostic markers expression and restraining the growth of mesothelial cells. For in vitro drug testing, MSE from five patients presented various drug sensitivities, and one case showed strong response to PD-1 checkpoint inhibition (pembrolizumab). For some patients, the application of combinatorial drugs had better therapeutic responses compared to monotherapy. Digitalised quantification of data offers a better understanding of different MSE culture models. More importantly, the proposed platforms are practical and amenable for performing in vitro chemo-/immunotherapeutic drug testing by using routine cytologic MSE in a personalised manner. Next to cell blocks, our work demonstrates the prognostic and predictive value of cytologic effusion samples.


Sport specificity of mental disorders: the issue of sport psychiatry.
The prevalence of psychiatric conditions among elite athletes is still under debate. More and more evidence has accumulated that high-performance athletes are not protected from mental disorders as previously thought. The authors discuss the issue of the sport specificity of selected mental diseases in elite athletes. Specific aspects of eating disorders, exercise addiction, chronic traumatic encephalopathy and mood disorders in the context of overtraining syndrome are examined. In particular, the interrelationship between life and work characteristics unique to elite athletes and the development of mental disorders are reviewed. Differences of clinical presentation and some therapeutic consequences are discussed. The authors suggest that the physical and mental strains endured by elite athletes might influence the onset and severity of their psychiatric disorder. Beside the existing research strategies dealing with the amount of exercise, its intensity and lack of recreation experienced by athletes, further research on psycho-social factors is needed to better understand the sport-specific aetiology of mental disorders in high-performance athletes.


A quantitative enzyme-linked immunoassay for serum immune complexes.
A sensitive, quantitative, non-complement dependent enzyme-linked immunoassay (ELIA) for human serum immune complexes has been developed utilizing the L1210 murine leukemia cell and peroxidase-conjugated anti-IgG. At end-point O-dianisidine dihydrochloride method was developed which detects as little as 16.45 x 10(-5) purpurogallin units of horse radish peroxidase. The L1210 ELIA requires only five microliters of serum and reproducibly quantitates as little as 55 nanograms of an artificial immune complex standard (heat aggregated IgG). The validity of using aggregated IgG as a standard was demonstrated by the fact that it produced a dose dependent inhibition of binding of a known immune complex (peroxidase-anti-peroxidase) to the L1210 cells whereas monomeric IgG showed no inhibition. Results of the L1210 ELIA are similar to those of the L1210 radioimmune assay (RIA) which we have previously reported. There was no significant difference in mean immune complex levels between the ELIA and the RIA when serums from normal healthy blood donors were tested. A strong correlation (rs equals +0.787) of immune complex levels as determined by the ELIA and the RIA was found in 17 serum samples from patients with disease associated with elevated levels of circulating immune complexes.


Design, synthesis, and evaluation of inhibitors of trypanosomal and leishmanial dihydrofolate reductase.
This paper concerns the design, synthesis, and evaluation of inhibitors of leishmanial and trypanosomal dihydrofolate reductase. Initially study was made of the structures of the leishmanial and human enzyme active sites to see if there were significant differences which could be exploited for selective drug design. Then a series of compounds were synthesized based on 5-benzyl-2, 4-diaminopyrimidines. These compounds were assayed against the protozoan and human enzymes and showed selectivity for the protozoan enzymes. The structural data was then used to rationalize the enzyme assay data. Compounds were also tested against the clinically relevant forms of the intact parasite. Activity was seen against the trypanosomes for a number of compounds. The compounds were in general less active against Leishmania. This latter result may be due to uptake problems. Two of the compounds also showed some in vivo activity in a model of African trypanosomiasis.


Selective admission into stroke unit and patient outcomes: a tale of four cities.
: Care of stroke patients costs considerably more in specialized stroke units (SU) compared to care in general medical wards (GMW) but the technology may be cost effective if it leads to significantly improved outcomes. While randomized control trials show better outcomes for stroke patients admitted to SU, observational studies report mixed findings. In this paper we use individual level data from first-ever stroke patients in four European cities and find evidence of selection by the initial severity of stroke into SU in some cities. In these cases, the impact of admission to SU on outcomes is overestimated by multivariate logit models even after controlling for case-mix. However, when the imbalance in patient characteristics and severity of stroke by admission to SU and GMW is adjusted using propensity score methods, the differences in outcomes are no longer statistically significant in most cases. Our analysis explains why earlier studies using observational data have found mixed results on the benefits of admission to SU.


Promotion of recovery from thoracic spinal cord contusion in rats by stimulation of medullary raphe or its midbrain input.
. Brainstem regions with descending axons could influence recovery after spinal cord injury, thus presenting potential targets for treatment. Neurons in the hindbrain raphe magnus respond to sensory and chemical concomitants of trauma (eg, pain, circulating cytokines) and release trophic substances (serotonin, neuropeptides) in widespread spinal regions. . The authors tested in rats whether intermittent stimulation of the raphe magnus or its major midbrain input, the periaqueductal gray, influences recovery from incomplete thoracic (T8) injury. . After a moderate weight-drop injury, an implanted wireless stimulator intermittently delivered cathodal pulses (8 Hz, 30 µA) through a microelectrode for 12 hours daily over multiple days. Stimulators in controls were inactive or not implanted. . Raphe magnus stimulation, started 1 to 2 hours after injury, enduringly improved open-field motor performance (measured weekly for 8 weeks) and footprint and gridwalk performance (measured in the 9th week). These improvements increased with days of stimulation (1-7). Myelinated axons in perilesional white matter and serotonin-containing terminals in gray matter, quantified 14 weeks postinjury, also increased. In separate parametric studies that examined open-field behavior following 14 days of stimulation, starting 2 days after injury was better than 7 days or 2 hours; starting at 8 weeks appeared ineffective. The periaqueductal gray, an established, safe stimulation target in man, similarly facilitated recovery of motor performance and myelination (but not serotonergic terminals) when stimulated for 4 to 7 days. . Raphe magnus neurons mediate restorative feedback in acute spinal cord injury. Their interim activation, direct or indirect (via periaqueductal gray), offers a basis for possible treatments in patients.


Hyperinflammation and Fibrosis in Severe COVID-19 Patients: Galectin-3, a Target Molecule to Consider.
COVID-19 disease have become so far the most important sanitary crisis in the XXI century. In light of the events, any clinical resource should be considered to alleviate this crisis. Severe COVID-19 cases present a so-called cytokine storm as the most life-threatening symptom accompanied by lung fibrosis. Galectin-3 has been widely described as regulator of both processes. Hereby, we present compelling evidences on the potential role of galectin-3 in COVID-19 in the regulation of the inflammatory response, fibrosis and infection progression. Moreover, we provide a strong rationale of the utility of measuring plasma galectin-3 as a prognosis biomarker for COVID-19 patients and propose that inhibition of galectin-3 represents a feasible and promising new therapeutical approach.


Mice 3D testicular organoid system as a novel tool to study Zika virus pathogenesis.
Zika virus (ZIKV) poses a serious threat to global public health due to its close relationship with neurological and male reproductive damage. However, deficiency of human testicular samples hinders the in-depth research on ZIKV-induced male reproductive system injury. Organoids are relatively simple in vitro models, which could mimic the pathological changes of corresponding organs. In this study, we constructed a 3D testicular organoid model using primary testicular cells from adult BALB/c mice. Similar to the testis, this organoid system has a blood-testis barrier (BTB)-like structure and could synthesize testosterone. ZIKV tropism of testicular cells and ZIKV-induced pathological changes in testicular organoid was also similar to that in mammalian testis. Therefore, our results provide a simple and reproducible in vitro testicular model for the investigations of ZIKV-induced testicular injury.


Cortical sources of resting state EEG rhythms are sensitive to the progression of early stage Alzheimer's disease.
Cortical sources of resting state electroencephalographic (EEG) rhythms are abnormal in subjects with Alzheimer's disease (AD). Here we tested the hypothesis that these sources are also sensitive to the progression of early stage AD over the course of one year. The resting state eyes-closed EEG data were recorded in 88 mild AD patients at baseline (Mini Mental State Evaluation, MMSE I = 21.7 ± 0.2 standard error, SE) and at approximately one-year follow up (13.3 months ± 0.5 SE; MMSE II = 20 ± 0.4 SE). All patients received standard therapy with acetylcholinesterase inhibitors. EEG recordings were also performed in 35 normal elderly (Nold) subjects as controls. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz). Cortical EEG sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Compared to the Nold subjects, the mild AD patients were characterized by a power increase of widespread delta sources and by a power decrease of posterior alpha sources. In the mild AD patients, the follow-up EEG recordings showed increased power of widespread delta sources as well as decreased power of widespread alpha and posterior beta 1 sources. These results suggest that the resting state EEG sources were sensitive, at least at group level, to the cognitive decline occurring in the mild AD group over a one-year period, and might represent cost-effective and non-invasive markers with which to enrich cohorts of AD patients that decline faster for clinical studies.


Individualized pattern recognition for detecting mind wandering from EEG during live lectures.
The ability to detect mind wandering as it occurs is an important step towards improving our understanding of this phenomenon and studying its effects on learning and performance. Current detection methods typically rely on observable behaviour in laboratory settings, which do not capture the underlying neural processes and may not translate well into real-world settings. We address both of these issues by recording electroencephalography (EEG) simultaneously from 15 participants during live lectures on research in orthopedic surgery. We performed traditional group-level analysis and found neural correlates of mind wandering during live lectures that are similar to those found in some laboratory studies, including a decrease in occipitoparietal alpha power and frontal, temporal, and occipital beta power. However, individual-level analysis of these same data revealed that patterns of brain activity associated with mind wandering were more broadly distributed and highly individualized than revealed in the group-level analysis. To apply these findings to mind wandering detection, we used a data-driven method known as common spatial patterns to discover scalp topologies for each individual that reflects their differences in brain activity when mind wandering versus attending to lectures. This approach avoids reliance on known neural correlates primarily established through group-level statistics. Using this method for individual-level machine learning of mind wandering from EEG, we were able to achieve an average detection accuracy of 80-83%. Modelling mind wandering at the individual level may reveal important details about its neural correlates that are not reflected when using traditional observational and statistical methods. Using machine learning techniques for this purpose can provide new insight into the varieties of neural activity involved in mind wandering, while also enabling real-time detection of mind wandering in naturalistic settings.


Understanding outcomes in family-based treatment for adolescent anorexia nervosa: a network approach.
Family-based treatment (FBT) is the first-line treatment for adolescent anorexia nervosa (AN). Yet, remission is not achieved for about half of adolescents with AN receiving FBT. Understanding patient- and parent-level factors that predict FBT response may inform treatment development and improve outcomes. Network analysis was used to identify the most central symptoms of AN in adolescents who completed the Eating Disorder Examination (EDE) prior to FBT (N = 409). Bridge pathways between adolescent AN and parental self-efficacy in facilitating their child's recovery from AN were identified in a subset of participants (n = 184). Central and bridge symptoms were tested as predictors of early response (⩾2.4 kg weight gain by the fourth session of FBT) and end-of-treatment weight restoration [⩾95% expected body weight (EBW)] and full remission (⩾95% EBW and EDE score within 1 standard deviation of norms). The most central symptoms of adolescent AN included desiring weight loss, dietary restraint, and feeling fat. These symptoms predicted early response, but not end-of-treatment outcomes. Bridge symptoms were parental beliefs about their responsibility to renourish their child, adolescent discomfort eating in front of others, and adolescent dietary restraint. Bridge symptoms predicted end-of-treatment weight restoration, but not early response nor full remission. Findings highlight the prognostic utility of core symptoms of adolescent AN. Parent beliefs about their responsibility to renourish their child may maintain associations between parental self-efficacy and AN psychopathology. These findings could inform strategies to adapt FBT and improve outcomes.


Geochemical environments, trace elements, and cardiovascular diseases.
Cardiovascular diseases are often found to be associated with certain physicochemical characteristics of the environment-namely, the hardness of the water and the types of rock and soil underlying the area. Areas supplied with soft water usually have higher cardiovascular death rates than do areas supplied with hard water. Evidence linking cardiovascular diseases with the geochemistry of rocks and soils is more limited. The nature of these associations is still speculative but it is possible that certain trace elements are involved, some being beneficial and others harmful. Further epidemiological studies to identify these various trace elements are desirable.


Diagnosed with a Rare Cancer: Experiences of Adult Sarcoma Survivors with the Healthcare System-Results from the SURVSARC Study.
The aim of this study was to explore the experience of rare cancer patients with the healthcare system and examine differences between age groups (adolescents and young adults (AYA, 18-39 years), older adults (OA, 40-69 years) and elderly (≥70 years)). Dutch sarcoma patients, 2-10 years after diagnosis, completed a questionnaire on their experience with the healthcare system, satisfaction with care, information needs, patient and diagnostic intervals (first symptom to first doctor's visit and first doctor's visit to diagnosis, respectively) and received supportive care. In total, 1099 patients completed the questionnaire (response rate 58%): 186 AYAs, 748 OAs and 165 elderly. Many survivors experienced insufficient medical and non-medical guidance (32% and 38%), although satisfaction with care was rated good to excellent by 94%. Both patient and diagnostic intervals were >1 month for over half of the participants and information needs were largely met (97%). AYAs had the longest patient and diagnostic intervals, experienced the greatest lack of (non-)medical guidance, had more desire for patient support groups and used supportive care most often. This nationwide study among sarcoma survivors showed that healthcare experiences differ per age group and identified needs related to the rarity of these tumors, such as improvements concerning (non-)medical guidance and diagnostic intervals.


Drug-induced hepatotoxicity of anti-tuberculosis drugs and their serum levels.
The correlation between serum anti-tuberculosis (TB) drug levels and the drug-induced hepatotoxicity (DIH) remains unclear. The purpose of this study was to investigate whether anti-TB DIH is associated with basal serum drug levels. Serum peak levels of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) were analyzed in blood samples 2 hr after the administration of anti-TB medication. Anti-TB DIH and mild liver function test abnormality were diagnosed on the basis of laboratory and clinical criteria. Serum anti-TB drug levels and other clinical factors were compared between the hepatotoxicity and non-hepatotoxicity groups. A total of 195 TB patients were included in the study, and the data were analyzed retrospectively. Seventeen (8.7%) of the 195 patients showed hepatotoxicity, and the mean aspartate aminotransferase/alanine aminotransferase levels in the hepatotoxicity group were 249/249 IU/L, respectively. Among the 17 patients with hepatotoxicity, 12 showed anti-TB DIH. Ten patients showed PZA-related hepatotoxicity and 2 showed INH- or RMP-related hepatotoxicity. However, intergroup differences in the serum levels of the 4 anti-TB drugs were not statistically significant. Basal serum drug concentration was not associated with the risk anti-TB DIH in patients being treated with the currently recommended doses of first-line anti-TB treatment drugs.


Usefulness of the SYNTAX score to predict "no reflow" in patients treated with primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.
The no-reflow phenomenon has been shown to have a significant effect on clinical outcomes in patients with acute ST-segment elevation myocardial infarction. Angiographic features incorporated in the SYNTAX Score (SXScore) obtained on diagnostic angiography during primary percutaneous coronary intervention (PPCI) may be associated with the occurrence of myocardial no-reflow. The aim of this study was to assess the ability of the SXScore to predict no-reflow during PPCI. The SXScore was applied to 669 consecutive patients presenting with acute ST-segment elevation myocardial infarction from November 2006 to February 2008. Angiographic analysis of the PPCI procedure was used to determine no-reflow. The median SXScore was 16 (range 9.5 to 23). No-reflow occurred in 77 patients (12%). On univariate logistic regression analysis, the SXScore showed a strong association (for each 10-unit increase in SXScore, odds ratio 1.42, 95% confidence interval 1.16 to 1.76, p <0.001). On multivariate logistic regression in a model including clinical variables, SXScore was an independent predictor of no-reflow (odds ratio 1.29, 95% confidence interval 1.02 to 1.63, p <0.001). Classification and regression tree analysis identified SXScore >21 as the best cutoff, with patients having double the risk for no-reflow compared to those with SXScore ≤21 (events 9% vs 18%, p = 0.006). In conclusion, the SXScore obtained in the diagnostic phase of PPCI for acute ST-segment elevation myocardial infarction can identify patients at risk for developing no-reflow.


Exploring Preschoolers' Emotions in Pediatric Dentistry.
Emotion is a feeling that someone can feel. Emotions are generally shown through behavior or facial expressions. Emotions are essential for dental treatment because there is a relation between the emotions felt by children and the success of the dental treatment that the dentist will give. This study aimed to describe variables of emotions about dental treatment. Descriptive analysis using a convenience nonrandom sampling technique was conducted on 58 preschool children aged 3 to 6 years old who came for dental treatment at the Bandung Dental Center in Bandung, Indonesia. The instrument used to ask children how they feel about dental care is a 7-item questionnaire derived from the children's fear survey scale-dental subscale. Meanwhile, the media used by children to respond was a card with facial expressions from the Facial Expression Emotion Scale. The results showed that only participants aged 4 responded with one type of emotion (happy), while the other age groups gave various emotional responses. Fear emotion began to appear in the age group of 5 and 6 years and only in girls, while emotions of anger also appeared in girls and only at the age of 5. In this study, the emotions that children choose about dental care at the Bandung Dental Center clinic are happy emotions. The emotions of fear and sadness were chosen more by girl participants, while none of the boy participants chose the emotion of fear. This sad and fearful response is associated with invasive dental treatment. Anger was chosen as a child's response dominantly because of the parents' invitation to the dentist.


[Kallikrein-kinin system parameters as markers of various adaptive capacities of the body in young male patients with mitral valve prolapse].
The activity of kinin system parameters was studied in 137 young male patients with mitral valve prolapse (MVP) in relation to the body's adaptive capacities. As compared with the controls, the patients with high (Group 1) and low (Group 2) adaptive capacities showed 57.08 and 79.14% increases in leukocyte elastase activity, respectively (p < 0.05). In Groups 1 and 2, the leukocyte elastase/alpha1-proteinase inhibitor ratio was 55.6% and by 2.16-fold higher, respectively, than in the controls (p < 0.05). Thus, the high the leukocyte elastase/alpha1-proteinase inhibitor ratio may serve as a biochemical marker of diminished adaptive capacities in young male patients with mitral valve prolapse and indicate a poor prognosis associated with degradation of a diversity of functionally significant proteins.


A Peeling Approach for Integrated Manufacturing of Large Monolayer h-BN Crystals.
Hexagonal boron nitride (h-BN) is the only known material aside from graphite with a structure composed of simple, stable, noncorrugated atomically thin layers. While historically used as a lubricant in powder form, h-BN layers have become particularly attractive as an ultimately thin insulator, barrier, or encapsulant. Practically all emerging electronic and photonic device concepts currently rely on h-BN exfoliated from small bulk crystallites, which limits device dimensions and process scalability. We here focus on a systematic understanding of Pt-catalyzed h-BN crystal formation, in order to address this integration challenge for monolayer h-BN via an integrated chemical vapor deposition (CVD) process that enables h-BN crystal domain sizes exceeding 0.5 mm and a merged, continuous layer in a growth time of less than 45 min. The process makes use of commercial, reusable Pt foils and allows a delamination process for easy and clean h-BN layer transfer. We demonstrate sequential pick-up for the assembly of graphene/h-BN heterostructures with atomic layer precision, while minimizing interfacial contamination. The approach can be readily combined with other layered materials and enables the integration of CVD h-BN into high-quality, reliable 2D material device layer stacks.


[Spiral computed tomography in chest injury].
The purpose of the study was to evaluate the potentialities of spiral computed tomography (SCT) in recognizing some symptoms of injury-induced chest changes, to define differential diagnostic signs of some complications occurring in the posttraumatic period. Thirty one studies were made in 23 victims with severe mixed chest injury upon their admissions and during follow-ups. CT data were analyzed on axial slices by means of multiplanar and three-dimensional reconstructions. CT angiography was applied in 8 cases. The CT picture of some pathological symptoms of chest injuries, injury complications, their differential diagnostic criteria were outlined.


Pyrazinamide susceptibility testing of Mycobacterium tuberculosis by high resolution melt analysis.
Pyrazinamide (PZA) plays the important role in shortening the tuberculosis treatment period and in treating MDR-TB. Phenotypic PZA susceptibility methods are limited because they require specialized acidified media, which increases costs and complexity. In this study we developed a genotypic high resolution melt (HRM) analysis technique to detect pncA mutations associated with PZA resistant Mycobacterium tuberculosis. Seven overlapping primer pairs were designed to cover the entire pncA gene and upstream regions. Each gene segment was individually amplified by real-time PCR followed by HRM analysis. The assay was evaluated on 98 clinical M. tuberculosis isolates (41 PZA susceptible by MGIT method, 55 PZA resistant, 2 undetermined). HRM was 94% concordant to full-length sequencing results, with most discrepancies attributable to mixed populations per HRM or transversions. Sequencing and HRM yielded 82% and 84% concordance, respectively, to phenotypic PZA susceptibilities by MGIT, with most discrepancies attributable to isolates with wild-type pncA but phenotypic PZA resistance. This HRM technique is a simple and high-throughput method for screening clinical M. tuberculosis samples for PZA resistance.


Neurofibromatosis type 1 and sporadic optic gliomas.
To compare the natural history of sporadic optic glioma with those associated with neurofibromatosis type 1 (NF1). Optic glioma cases were identified using both the Manchester Children's Tumour Registry (CTR) and the North West Regional NF1 Database (NF1DB), with detailed information on natural history available from the former (in 34 of 36 cases identified). A total of 52 cases over a period of 41 years were identified. From the 34 whose natural history was known, almost all (n = 31) were symptomatic, with mean ages of presentation of 4.5 and 5.1 years for NF1 and sporadic cases respectively. The majority (n = 22) presented with visual impairment, seven of whom were blind in at least one eye. Sporadic cases were over twice as likely as NF1 to have visual impairment. Recurrence occurred in 12 patients. Fewer NF1 patients died as a direct result of their optic glioma, but overall mortality and 5 and 10 year survival rates between the two groups were similar. All five primary (non-metastatic) second central nervous system (CNS) tumours occurred in NF1 cases, two of these following radiotherapy. Symptomatic sporadic optic gliomas presented with impaired vision more frequently and were more aggressive than NF1 optic gliomas. Only optic glioma cases with NF1 were at risk of developing a second CNS tumour. Aggressive treatment of sporadic optic gliomas and early surveillance of NF1 optic gliomas may be required. The use of radiotherapy in these children requires further clarification.


Polo-like kinase 1 as target for cancer therapy.
Polo-like kinase 1 (Plk1) is an interesting molecule both as a biomarker and as a target for highly specific cancer therapy for several reasons. Firstly, it is over-expressed in many cancers and can serve as a biomarker to monitor treatment efficacy of Plk1 inhibitors. Furthermore, the Plk1 enzyme is expressed only in dividing cells and is a major regulator of the cell cycle. It controls entry into mitosis and regulates the spindle checkpoint. The expression of Plk1 in normal cells is not nearly as strong as that in cancer cells, which makes Plk1 a discriminating tartget for the development of cancer-specific small molecule drugs. RNA interference experiments in vitro and in vivo have indicated that downregulation of Plk1 expression represents an attractive concept for cancer therapy. Over the years, a number of Plk1 inhibitors have been discovered. Many of these inhibitors are substances that compete with ATP for the substrate binding site. The ATP-competitive inhibitor BI 6727 is currently being clinically tested in cancer patients. Another drug in development, poloxin, is the first Polo-box domain inhibitor of Plk1. This compound is a derivative of the natural product, thymoquinone, derived from Nigella sativa. A novel and promising strategy is to synthesize bifunctional inhibitors that combine the high binding affinity of ATP inhibitors with the specificity of competitive inhibitors.


Bayesian classification for data from the same unknown class.
In this paper, we address the problem of how to classify a set of query vectors that belong to the same unknown class. Sets of data known to be sampled from the same class are naturally available in many application domains, such as speaker recognition. We refer to these sets as homologous sets. We show how to take advantage of homologous sets in classification to obtain improved accuracy over classifying each query vector individually. Our method, called homologous naive Bayes (HNB), is based on the naive Bayes classifier, a simple algorithm shown to be effective in many application domains. RNB uses a modified classification procedure that classifies multiple instances as a single unit. Compared with a voting method and several other variants of naive Bayes classification, HNB significantly outperforms these methods in a variety of test data sets, even when the number of query vectors in the homologous sets is small. We also report a successful application of HNB to speaker recognition. Experimental results show that HNB can achieve classification accuracy comparable to the Gaussian mixture model (GMM), the most widely used speaker recognition approach, while using less time for both training and classification.


Toward Alginate-Based Membrane Technology for High Performance Recovery of Heavy Metals in Cells.
One of the major environmental problems is a global metal contamination. Heavy metals are nonbiodegradable and tend to accumulate in living organisms. Therefore, searching for biocompatible materials with enhanced sorption capabilities for selective removal of toxic elements from complex environments, low cost, ease of operation, and large available quantities that meet all requirements of the Green Chemistry concept is a current engineering and analytical task. We present a comprehensive study toward construction of an advanced biomembrane-based technology for recovery of several heavy metals and ruthenium by microdimensional alginate scaffolds. The chosen design of alginate scaffolds and their operational conditions were monitored during removal of Cd(II), Co(II), Pb(II), As(III), and Ru(III) in modeled aqueous solutions, cell culture medium, and in the presence of A549 lung cells by a tandem of biological (live/dead cell test), physical nanoanalytical (TEM/EDX, SEM/EDX), and chemical (FT-IR, HR-ICP-MS) assays. More precisely, the impact of certain experimental conditions, viz., medium acidity and matrix effects on sorption capacity of the above-mentioned elements, was investigated in detail. Remarkably, a different attachment behavior during adsorption of chosen elements by alginate scaffolds was observed. In addition, we revealed an essential concentration dependent effect of loaded heavy metals and ruthenium on cultivated cells. The obtained data allow us to gain a deeper insight into the interactions occurring in the studied biomaterial-inorganic system. Moreover, the obtained dependencies can be widely used for the development of alginate-based membrane technology employed for the protection of environmental and biological samples from the toxic pollutants.


Assessment of Rapid Hepatic Glycogen Synthesis in Humans Using Dynamic 13C Magnetic Resonance Spectroscopy.
Carbon-13 magnetic resonance spectroscopy (MRS) following oral intake of 13C-labeled glucose is the gold standard for imaging glycogen metabolism in humans. However, the temporal resolution of previous studies has been >13 minutes. Here, we describe a high-sensitivity 13C MRS method for imaging hepatic glycogen synthesis with a temporal resolution of 1 minute or less. Nuclear magnetic resonance spectra were acquired from the liver of 3 healthy volunteers, using a 13C clamshell radiofrequency transmit and paddle-shaped array receive coils in a 3 Tesla magnetic resonance imaging system. Following a 15-minute baseline 13C MRS scan of the liver, [1-13C]-glucose was ingested and 13C MRS data were acquired for an additional 1-3 hours. Dynamic change of the hepatic glycogen synthesis level was analyzed by reconstructing the acquired MRS data with temporal resolutions of 30 seconds to 15 minutes. Plasma levels of 13C-labeled glucose and lactate were measured using gas chromatography-mass spectrometry. While not detected at baseline 13C MRS, [1-13C]-labeled α-glucose and β-glucose and glycogen peaks accumulated rapidly, beginning as early as ~2 minutes after oral administration of [1-13C]-glucose. The [1-13C]-glucose signals peaked at ~5 minutes, whereas [1-13C]-glycogen peaked at ~25 minutes after [1-13C]-glucose ingestion; both signals declined toward baseline levels over the next 1-3 hours. Plasma levels of 13C-glucose and 13C-lactate rose gradually, and approximately 20% of all plasma glucose and 5% of plasma lactate were 13C-labeled by 2 hours after ingestion. Conclusion: We observed rapid accumulation of hepatic [1-13C]-glycogen following orally administered [1-13C]-glucose, using a dynamic 13C MRS method with a temporal resolution of 1 minute or less. Commercially available technology allows high temporal resolution studies of glycogen metabolism in the human liver.


Extended-stay rounds can help move patients along.
Weekly extended stay rounds help move along patients who have issues and barriers to a timely discharge, experts say. They recommend: Hold them at the same time and place each week and schedule an hour to an hour and a half for each meeting. Include the physician advisor for case management, a financial counselor, and representatives from case management, social work, therapy, nutrition, pharmacy, wound care, and other departments providing services to patients. Talk about the barriers and issues impeding discharge and brainstorm on solutions.


GRK1-dependent phosphorylation of S and M opsins and their binding to cone arrestin during cone phototransduction in the mouse retina.
The shutoff mechanisms of the rod visual transduction cascade involve G-protein-coupled receptor (GPCR) kinase 1 (GRK1) phosphorylation of light-activated rhodopsin (R*) followed by rod arrestin binding. Deactivation of the cone phototransduction cascade in the mammalian retina is delineated poorly. In this study we sought to explore the potential mechanisms underlying the quenching of the phototransduction cascade in cone photoreceptors by using mouse models lacking rods and/or GRK1. Using the "pure-cone" retinas of the neural retina leucine zipper (Nrl) knock-out (KO, -/-) mice (Mears et al., 2001), we have demonstrated the light-dependent, multi-site phosphorylation of both S and M cone opsins by in situ phosphorylation and isoelectric focusing. Immunoprecipitation with affinity-purified polyclonal antibodies against either mouse cone arrestin (mCAR) or mouse S and M cone opsins revealed specific binding of mCAR to light-activated, phosphorylated cone opsins. To elucidate the potential role of GRK1 in cone opsin phosphorylation, we created Nrl and Grk1 double knock-out (Nrl-/-Grk1-/-) mice by crossing the Nrl-/- mice with Grk1-/- mice (Chen et al., 1999). We found that, in the retina of these mice, the light-activated cone opsins were neither phosphorylated nor bound with mCAR. Our results demonstrate, for the first time in a mammalian species, that cone opsins are phosphorylated and that CAR binds to phosphorylated cone opsins after light activation.


Satellite cell dysfunction contributes to the progressive muscle atrophy in myotonic dystrophy type 1.
Myotonic dystrophy type 1 (DM1), one of the most common forms of inherited neuromuscular disorders in the adult, is characterized by progressive muscle weakness and wasting leading to distal muscle atrophy whereas proximal muscles of the same patients are spared during the early phase of the disease. In this report, the role of satellite cell dysfunction in the progressive muscular atrophy has been investigated. Biopsies were obtained from distal and proximal muscles of the same DM1 patients. Histological and immunohistological analyses were carried out and the past regenerative history of the muscle was evaluated. Satellite cell number was quantified in vivo and proliferative capacity was determined in vitro. The size of the CTG expansion was positively correlated with the severity of the symptoms and the degree of muscle histopathology. Marked atrophy associated with typical DM1 features was observed in distal muscles of severely affected patients whereas proximal muscles were relatively spared. The number of satellite cells was significantly increased (twofold) in the distal muscles whereas very little regeneration was observed as confirmed by telomere analyses and developmental MyHC staining (0.3-3%). The satellite cells isolated from the DM1 distal muscles had a reduced proliferative capacity (36%) and stopped growing prematurely with telomeres longer than control cells (8.4 vs. 7.1 kb), indicating that the behaviour of these precursor cells was modified. Our results indicate that alterations in the basic functions of the satellite cells progressively impair the muscle mass maintenance and/or regeneration resulting in gradual muscular atrophy.


Increasing frequency of opioid prescriptions for chronic abdominal pain in US outpatient clinics.
Opioids are sometimes used to treat chronic abdominal pain. However, opioid analgesics have not been proven to be an effective treatment for chronic abdominal pain and have been associated with drug misuse, constipation, and worsening abdominal pain. We sought to estimate the national prescribing trends and factors associated with opioid prescribing for chronic abdominal pain. Chronic abdominal pain-related visits by adults to US outpatient clinics were identified using reason-for-visit codes from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (1997-2008). Data were weighted to produce national estimates of opioid prescriptions over time. Logistic regression analyses, adjusted for complex survey design, were performed to identify factors associated with opioid use. The number of outpatient visits for chronic abdominal pain consistently decreased over time from 14.8 million visits (95% confidence interval [CI], 11.6-18.0 visits) in 1997 through 1999 to 12.2 million visits (95% CI, 9.0-15.6 visits) or 1863 visits per 100,000 population in 2006 through 2008 (P for trend = 0.04). Conversely, the adjusted prevalence of visits for which an opioid was prescribed increased from 5.9% (95% CI, 3.5%-8.3%) in 1997 through 1999 to 12.2% (95% CI, 7.5%-17.0%) in 2006 through 2008 (P = 0.03 for trend). Opioid prescriptions were most common among patients aged 25 to 40 years old (odds ratio [OR] 4.6; 95% CI, 1.2-18.4). Opioid prescriptions were less common among uninsured (OR 0.1; 95% CI, 0.04-0.40) and African American (OR 0.3; 95% CI, 0.1-0.9) patients. From 1997 to 2008 opioid prescriptions for chronic abdominal pain more than doubled. Further studies are needed to better understand the reasons for and consequences of this trend.


Photoactivation of the photoactive yellow protein: why photon absorption triggers a trans-to-cis Isomerization of the chromophore in the protein.
Atomistic QM/MM simulations have been carried out on the complete photocycle of Photoactive Yellow Protein, a bacterial photoreceptor, in which blue light triggers isomerization of a covalently bound chromophore. The "chemical role" of the protein cavity in the control of the photoisomerization step has been elucidated. Isomerization is facilitated due to preferential electrostatic stabilization of the chromophore's excited state by the guanidium group of Arg52, located just above the negatively charged chromophore ring. In vacuo isomerization does not occur. Isomerization of the double bond is enhanced relative to isomerization of a single bond due to the steric interactions between the phenyl ring of the chromophore and the side chains of Arg52 and Phe62. In the isomerized configuration (ground-state cis), a proton transfer from Glu46 to the chromophore is far more probable than in the initial configuration (ground-state trans). It is this proton transfer that initiates the conformational changes within the protein, which are believed to lead to signaling.


Brain and atrial natriuretic peptides bind to common receptors in brain capillary endothelial cells.
The recent discovery of brain natriuretic peptides (BNP) that stimulates natriuresis, diuresis, and vascular smooth muscle relaxation in a manner similar to that of atrial natriuretic peptide (ANP) suggests the possibility that these endocrine hormones function via some common mechanism. Indirect evidence from several laboratories suggests that BNP and ANP may bind to the same receptors. We examined whether ANP and BNP bind to a common set of receptors in cultured bovine brain capillary endothelial cells and in bovine aortic endothelial cells. Scatchard plot analysis of binding data shows a similar dissociation constant (KD) of approximately 0.3 nM and a maximal binding capacity (Bmax) of 50 fmol/mg protein for both natriuretic peptides in brain capillary cells and 0.6 nM and 80 fmol/mg protein, respectively, in the aortic endothelial cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the affinity cross-linked receptor-ligand complex shows a strongly labeled 65-kDa receptor and a 125-kDa band that is likely to be a receptor of the guanylate cyclase type. ANP and BNP cross compete equally for binding to the two receptors identified on the gels. ANP and BNP also stimulate guanosine 3', 5'-cyclic monophosphate production in these cells, consistent with the presence of a functional guanylate cyclase-linked B receptor. We conclude that ANP and BNP share common receptors in brain capillary and aortic endothelial cells.


Pretransplant sequential hypo- and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin-based oxygen carrier perfusion solution.
Ex situ dual hypothermic oxygenated machine perfusion (DHOPE) and normothermic machine perfusion (NMP) of donor livers may have a complementary effect when applied sequentially. While DHOPE resuscitates the mitochondria and increases hepatic adenosine triphosphate (ATP) content, NMP enables hepatobiliary viability assessment prior to transplantation. In contrast to DHOPE, NMP requires a perfusion solution with an oxygen carrier, for which red blood cells (RBC) have been used in most series. RBC, however, have limitations and cannot be used cold. We, therefore, established a protocol of sequential DHOPE, controlled oxygenated rewarming (COR), and NMP using a new hemoglobin-based oxygen carrier (HBOC)-based perfusion fluid (DHOPE-COR-NMP trial, NTR5972). Seven livers from donation after circulatory death (DCD) donors, which were initially declined for transplantation nationwide, underwent DHOPE-COR-NMP. Livers were considered transplantable if perfusate pH and lactate normalized, bile production was ≥10 mL and biliary pH > 7.45 within 150 minutes of NMP. Based on these criteria five livers were transplanted. The primary endpoint, 3-month graft survival, was a 100%. In conclusion, sequential DHOPE-COR-NMP using an HBOC-based perfusion fluid offers a novel method of liver machine perfusion for combined resuscitation and viability testing of suboptimal livers prior to transplantation.


[Neurochemical mechanisms of reinforcement].
Literature and author's data are discussed concerning the participation of catecholaminergic mechanisms of brain in the control of chemoreactive properties of cerebral neurones. It is supposed that the basis of changes in properties of neurones involved in formation of temporary connection is an activation of catecholaminergic--reinforcing--neuro-transmitter mechanisms and coerulo-telencephalic system in particular. The importance of the interaction between neuro-transmitter systems and neuropeptides in the neurochemical ensurance of reinforcement is also stressed.


[Interrelation of matrix vesicles with spatial distribution of mineral component in fibrous and hyaline cartilages].
Mineral components of the human fibrous and hyaline cartilages were studied by the methods of light, scanning, transmission electron microscopy and cryofractography. The interterritorial matrix of the fibrous cartilage was found to contain not only the local deposits of mineral in matrix vesicles, but also the calcified collagen fibrils and interfibrillar spaces forming the collagen fibers and occupying its major part. In the hyaline cartilage and in the territorial matrix of fibrous cartilage, mineral deposits were located in mineralized conglomerates, the basis of which was formed by matrix vesicles, surrounded by collagen fibrils and interfibrillar space substance. Such conglomerates participate in the formation of calcospherites.


[Description of Mycobacterium tuberculosis mutations conferring resistance to rifampicin and isoniazid detected by GenoType® MTBDRplus V.2 in Colombia].
The GenoType®MTBDRplusV.2 assay is a molecular technique endorsed by the World Health Organization and the Pan American Health Organization that allows for the identification of the Mycobacterium tuberculosis complex and the detection of mutations in the rpoβ gene for rifampicin resistance, and katG and inhA genes for isoniazid resistance. Due to the genetic variability in the circulating strains around the world, the national tuberculosis control programs should assess the performance of these new diagnostic technologies and their use under program conditions as rapid tests. To describe the mutations identified by the GenoType®MTBDRplusV.2 assay in pulmonary samples and Mycobacterium tuberculosis isolates in the Laboratorio Nacional de Referencia of the Instituto Nacional de Salud in 2014. We conducted a retrospective, descriptive study to detect the expression of inhA, KatG and rpoβ genes, responsible for resistence against isoniazid and rifampicin using the GenoType® MTBDRplus V.2 assay in 837 samples and isolates from tuberculosis cases. Several mutations in the rpoβ gene were identified. Ser531Leu was the most frequent (36.6%) followed by Asp516Val (21.6%), while Ser315Thr1 was the most frequent mutation in the katG gene (91.9%). We were able to identify different mutations present in MDR-TB strains in the country, with frequencies similar to those reported in other countries in the South American region.


Circulating bilirubin and defense against kidney disease and cardiovascular mortality: mechanisms contributing to protection in clinical investigations.
Unconjugated bilirubin is an endogenous circulating antioxidant, bound to albumin, and therefore is retained in the vascular compartment. Bilirubin has well-documented neurotoxic effects in infants; however, current evidence indicates mildly elevated bilirubin is associated with protection from cardiovascular disease and all-cause mortality in adults. Recent clinical studies show mildly elevated bilirubin is associated with protection from kidney damage and dysfunction, in addition to cardiovascular events and all-cause mortality in patients undergoing hemodialysis. This is the first review to examine the clinical evidence and summarize the potential mechanisms of action that link bilirubin to protection from kidney damage, subsequent kidney failure, and dialysis-related mortality. With this understanding, it is hoped that new therapies will be developed to prevent renal dysfunction and mortality from cardiovascular disease in at-risk individuals.


Benzhexol-dependence resulting from self-medication for intermittent explosive disorder.
Objective. Recent observations in Iraq during the period of sanction suggest the existence of benzhexol prescribing linked to its calming effects on explosive behaviours. This inspired our group to research the existence of this practice and the characteristics of those involved in it. Method. All patients from the psychiatric service in Merjan Hospital, Al Hilla City, Babylon Governate, Iraq, who had a prescription for benzhexol between January 1991 and December 2000, were identified. All participants received their diagnosis based on the clinical criteria of the DSM-IV, after taking a comprehensive medical and psychiatric history, mental state examination and collateral information from family members. The patients were evaluated by the same qualified consultant psychiatrist at the initial assessment and all through the period of follow-up. Results. In the 10-year period under study, 354 patients were prescribed benzhexol. A total of 190 patients diagnosed as intermittent explosive disorder (IED) and 164 suffering from severe mental disorders or personality disorders were excluded from the study. The average age of the IED group was 29.5 years. On direct questioning, the main reason patients gave most frequently for using benzhexol was to control the aggressive outbursts (N=92, 48.4), to get high (N=49, 25.8), to relax (N=26, 13.7), to get rid of boredom (N=23, 12.1). In total, the whole group were prescribed benzhexol, at an average dose of 12.5 mg/day (range 2-20 mg/day). At the time of final assessment the mean dose of prescribed benzhexol had fallen slightly to 12 mg/day (2-20 mg/day), with 10 patients being benzhexol free. Of the 190, three patients had a diagnosis of obsessive compulsive disorders, 36 patients had a diagnosis of benzodiazepines dependence, and a further five had a diagnosis of alcohol dependency syndrome. Eighty percent felt satisfied with the effect of the drug and 95 were not motivated to stop it. Conclusions. There are a significant number of patients who are routinely prescribed benzhexol as a replacement therapy. The main original reason for starting it is to control outbursts and improves their reaction to stress situations. This growing issue raises the need for awareness, by both public and medical practitioners, of the potential adverse effects of benzhexol and its untoward consequences.


Evaluation of soybean oil quality during conventional frying by FTIR and some chemical indexes.
Conventional deep fat frying is a common food preparation technique in Mauritius. The deterioration of soybean oil, commonly used in conventional frying, has been studied during frying of potato chips. The oil was subjected to continuous frying at 180 degrees C for a total of 600 min. The quality changes in soybean oil were evaluated at 90 min interval by Fourier transform infrared (FTIR) spectroscopy and some routine chemical parameters, namely peroxide value, iodine value and free fatty acid. An increase in hydroperoxide and free fatty acid concentration has been observed during the frying process by FTIR technique and the chemical parameters, peroxide value and free fatty acid respectively. A significant decrease in triglyceride ester linkage was observed by FTIR. The linear decrease noted for iodine value (P < 0.01) indicated a general loss of unsaturation. Furthermore, FTIR studies showed a loss of cis double bonds along with an increase in trans unsaturation. The formation of unsaturated aldehyde has also been observed during the frying process by FTIR technique.


Activation of metabotropic glutamate receptor 3 modulates thalamo-accumbal transmission and rescues schizophrenia-like physiological and behavioral deficits.
Polymorphisms in the gene encoding for metabotropic glutamate receptor 3 (mGlu3 receptor) are associated with an increased likelihood of schizophrenia diagnosis and can predict improvements in negative symptoms following treatment with antipsychotics. However, the mechanisms by which mGlu3 receptors can regulate brain circuits involved in schizophrenia pathophysiology are not clear. We employed selective pharmacological tools and a variety of approaches including whole-cell patch-clamp electrophysiology, slice optogenetics, and fiber photometry to investigate the effects of mGlu3 receptor activation on phencyclidine (PCP)-induced impairments in thalamo-accumbal transmission and sociability deficits. A chemogenetic approach was used to evaluate the role of thalamo-accumbal transmission in PCP-induced sociability deficits. We first established that PCP treatment augmented excitatory transmission onto dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) in the nucleus accumbens (NAc), and induced sociability deficits. Our studies revealed a selective increase in glutamatergic synaptic transmission from thalamic afferents to D1-MSNs in the NAc shell. Chemogenetic silencing of thalamo-accumbal inputs rescued PCP-induced sociability deficits. Pharmacological activation of mGlu3 receptors normalized PCP-induced impairments in thalamo-accumbal transmission and sociability deficits. Mechanistic studies revealed that mGlu3 receptor activation induced robust long-term depression at synapses from the thalamic projections onto D1-MSNs in the NAc shell. These data demonstrate that activation of mGlu3 receptors decreases thalamo-accumbal transmission and thereby rescues sociability deficits in mouse modeling schizophrenia-like symptoms. These findings provide novel insights into the NAc-specific mechanisms and suggest that agents modulating glutamatergic signaling in the NAc may provide a promising approach for treating negative symptoms in schizophrenia.


Telbivudine attenuates gentamicin-induced kidney injury in rats.
Nephrotoxicity has been associated with nucleos(t)ide analogues other than telbivudine (LdT). This study investigated the potential effects of LdT and lamivudine (LAM) on renal function in an experimental rat model of gentamicin-induced acute nephrotoxicity. A total of 28 healthy Wistar albino rats were randomly divided into four experimental groups: negative control; positive control (PC); LdT; and LAM. Nephrotoxicity was induced by gentamicin in the LdT, LAM and PC groups. LdT and LAM were administered to two groups for 6 weeks starting on the ninth day. Blood samples were collected weekly and cystatin C levels were measured by ELISA. Animals were sacrificed on the 50th day and the kidneys were removed for histological examination. Serum cystatin C levels differed significantly between the LdT and LAM groups (P <0.007) and between the LdT and PC groups (P <0.001). Renal function was significantly improved in the LdT group at the start of antiviral treatment on Day 8 and at the end of treatment on Day 50 (P = 0.001 and 0.007). Glomerular injury, acute tubular necrosis and total injury score were significantly reduced in the LdT group relative to the PC and LAM groups upon histopathological examination. LdT was associated with significant improvements in renal function as measured by biochemical and histopathological methods. The acute kidney injury model data should be supported by clinical studies to suggest that LdT treatment may have advantages for patients with underlying chronic kidney disease receiving chronic hepatitis B treatment.


Nitrogen deprivation promotes Populus root growth through global transcriptome reprogramming and activation of hierarchical genetic networks.
We show a distinct and previously poorly characterized response of poplar (Populus tremula × Populus alba) roots to low nitrogen (LN), which involves activation of root growth and significant transcriptome reprogramming. Analysis of the temporal patterns of enriched ontologies among the differentially expressed genes revealed an ordered assembly of functionally cohesive biological events that aligned well with growth and morphological responses. A core set of 28 biological processes was significantly enriched across the whole studied period and 21 of these were also enriched in the roots of Arabidopsis thaliana during the LN response. More than half (15) of the 28 processes belong to gene ontology (GO) terms associated with signaling and signal transduction pathways, suggesting the presence of conserved signaling mechanisms triggered by LN. A reconstruction of genetic regulatory network analysis revealed a sub-network centered on a PtaNAC1 (P. tremula × alba NAM, ATAF, CUC 1) transcription factor. PtaNAC1 root-specific up-regulation increased root biomass and significantly changed the expression of the connected hub genes specifically under LN. Our results provide evidence that the root response to LN involves hierarchically structured genetic networks centered on key regulatory factors. Targeting these factors via genetic engineering or breeding approaches can allow dynamic adjustment of root architecture in response to variable nitrogen availabilities in the soil.


Is there a cryptic species of the golden snapper (Lutjanus johnii)?
For centuries, morphology-based fish identification has been applied without molecular evaluation. Many studies showed that specimens with a similar morphology are frequently found to be quite genetically distinct. One of the fish species that still remains taxonomically problematic is a commercial snapper species, Lutjanus johnii. Because of morphological ambiguities among local fish taxonomists in Malaysia, we examined the ability of the cytochrome oxidase I (COI) gene to genetically examine the taxonomic status of L. johnii. A 626-base pair COI region was successfully amplified and aligned with conspecific sequences that were retrieved from GenBank. The phylogenetic tree obtained showed two major clusters; the first cluster consists of L. johnii from Straits of Malacca, Thailand, Australia, and China while the second cluster comprises L. johnii from China and India. The latter group showed sequence divergence greater than 3.5%. After observing this, we suspected that there might be a cryptic species between the South China Sea and Indian Ocean. This is the first molecular report concerning the commercial species of snapper, L. johnii, in Malaysia, which had only gained provisional recognition from morphological examination.


Inhibiting three-body recombination in atomic Bose-Einstein condensates.
We discuss the possibility of inhibiting three-body recombination in atomic Bose-Einstein condensates via the application of resonant 2pi laser pulses. These pulses result in the periodic change in the phase of the molecular state by pi, which leads to destructive interference between the decay amplitudes following successive pulses. We show that the decay rate can be reduced by several orders of magnitude under realistic conditions.


Alcohol consumption in patients with primary sclerosing cholangitis.
To assess the alcohol drinking patterns in a cohort of primary sclerosing cholangitis (PSC) patients and the possible influence on the development of fibrosis. Ninety-six patients with PSC were evaluated with a validated questionnaire about a patient's lifetime drinking habits: the lifetime drinking history (LDH) questionnaire. In addition, clinical status, transient elastography and biochemistry values were analysed and registered. Patients were defined as having either significant or non-significant fibrosis. Significant fibrosis was defined as either an elastography value of ≥ 17.3 kPa or the presence of clinical signs of cirrhosis. Patients were divided into two groups depending on their alcohol consumption patterns; no/low alcohol consumption (one drink or unit/d) and moderate/high alcohol consumption (≥ 1 drink or unit/d). LDH data were calculated to estimate lifetime alcohol intake (LAI), current alcohol intake, drinks per year before and after diagnosis of PSC. We also calculated the number of episodes of binge-drinking (defined as consuming ≥ 5 drinks per occasion) in total, before and after the diagnosis of PSC. The mean LAI was 3882 units of alcohol, giving a mean intake after onset of alcohol consumption of 2.6 units per week. Only 9% of patients consumed alcohol equal to or more than one unit per day. Current alcohol intake in patients with significant fibrosis (n = 26) was less than in patients without significant fibrosis (n = 70), as shown by lower values of phosphatidylethanol (B-PEth) (0.1 μmol/L vs 0.33 μmol/L, respectively, P = 0.002) and carbohydrate-deficient transferrin (CDT) (0.88% vs 1.06%, respectively, P = 0.02). Self-reported LAI was similar between the two groups. Patients with significant fibrosis reduced their alcohol intake after diagnosis from 103 to 88 units per year whereas patients without fibrosis increased their alcohol intake after PSC diagnosis from 111 to 151 units/year. There were no correlations between elastography values and intake of alcohol (units/year) (r = -0.036). PSC patients have low alcohol consumption. The lack of correlation between fibrosis and alcohol intake indicates that a low alcohol intake is safe in these patients.


Shaping segments: Hox gene function in the genomic age.
Despite decades of research, morphogenesis along the various body axes remains one of the major mysteries in developmental biology. A milestone in the field was the realisation that a set of closely related regulators, called Hox genes, specifies the identity of body segments along the anterior-posterior (AP) axis in most animals. Hox genes have been highly conserved throughout metazoan evolution and code for homeodomain-containing transcription factors. Thus, they exert their function mainly through activation or repression of downstream genes. However, while much is known about Hox gene structure and molecular function, only a few target genes have been identified and studied in detail. Our knowledge of Hox downstream genes is therefore far from complete and consequently Hox-controlled morphogenesis is still poorly understood. Genome-wide approaches have facilitated the identification of large numbers of Hox downstream genes both in Drosophila and vertebrates, and represent a crucial step towards a comprehensive understanding of how Hox proteins drive morphological diversification. In this review, we focus on the role of Hox genes in shaping segmental morphologies along the AP axis in Drosophila, discuss some of the conclusions drawn from analyses of large target gene sets and highlight methods that could be used to gain a more thorough understanding of Hox molecular function. In addition, the mechanisms of Hox target gene regulation are considered with special emphasis on recent findings and their implications for Hox protein specificity in the context of the whole organism.


Undulations in tubular origami tessellations: A connection to area-preserving maps.
Origami tessellations, whose crease pattern has translational symmetries, have attracted significant attention in designing the mechanical properties of objects. Previous origami-based engineering applications have been designed based on the "uniform-folding" of origami tessellations, where the folding of each unit cell is identical. Although "nonuniform-folding" allows for nonlinear phenomena that are impossible through uniform-folding, there is no universal model for nonuniform-folding, and the underlying mathematics for some observed phenomena remains unclear. Wavy folded states that can be achieved through nonuniform-folding of the tubular origami tessellation called a waterbomb tube are an example. Recently, the authors formulated the kinematic coupled motion of unit cells within a waterbomb tube as the discrete dynamical system and identified a correspondence between its quasiperiodic solutions and wavy folded states. Here, we show that the wavy folded state is a universal phenomenon that can occur in the family of rotationally symmetric tubular origami tessellations. We represent their dynamical system as the composition of the two 2D mappings: taking the intersection of three spheres and crease pattern transformation. We show the universality of the wavy folded state through numerical calculations of phase diagrams and a geometric proof of the system's conservativeness. Additionally, we present a non-conservative tubular origami tessellation, whose crease pattern includes scaling. The result demonstrates the potential of the dynamical system model as a universal model for nonuniform-folding or a tool for designing metamaterials.