Revealing the Chemical Reaction Properties of a SiHCl3 Pyrolysis System by the ReaxFF Molecular Dynamics Method.
The pyrolysis kinetics of SiHCl3 and its reaction mechanism are essential for the chemical vapor deposition process in polysilicon industries. However, due to the high temperature and lack of in situ experimental detection technology, it is difficult to carry out experimental research on the pyrolysis kinetics of SiHCl3. In this work, reactive force field molecular dynamics simulations of SiHCl3 pyrolysis were performed to investigate the effect of temperature on the pyrolysis kinetics of SiHCl3 at the atomistic scale in a wide temperature range (1000-2000 K). The lumped Si clusters containing more than five Si atoms tended to appear at the later period of the reaction under a temperature lower than 1300 K, some of which even possessed polycyclic structures; nevertheless, small ones with less than two Si atoms such as SiHCl2 and HCl tended to emerge under a high temperature. The changes of partial energy terms with time evolution under various temperatures were proved to be rooted in the distribution of intermediates based on the momentary simulation period. In general, the reaction network at a low temperature was more complicated than that at a high temperature, resulting from the fact that more chemical events and intermediates came into existence, and the maximum number of Si atoms in one single molecule/radical was observed under a low temperature than that under a high temperature. As to the variation of SiHCl3 with the progress of the reaction, the linear fitting tendency disappeared under the temperature above 1300 K, which changed in fluctuation with the further elevation of temperature, elucidating the fact that SiHCl3 can act as a product and not just as a reactant to participate in elementary chemical events frequently.


Development of lentiviral vectors with optimized transcriptional activity for the gene therapy of patients with Fanconi anemia.
Fanconi anemia (FA) is an inherited genetic disease characterized mainly by bone marrow failure and cancer predisposition. Although gene therapy may constitute a good therapeutic option for many patients with FA, none of the clinical trials so far developed has improved the clinical status of these patients. We have proposed strategies for the genetic correction of bone marrow grafts from patients with FA, using lentiviral vectors (LVs). Here we investigate the relevance of the expression of FANCA to confer a therapeutic effect in cells from patients with FA-A, the most frequent complementation group in FA. Our data show that relatively weak promoters such as the vav or phosphoglycerate kinase (PGK) promoter confer, per copy of FANCA, physiological levels of FANCA mRNA in lymphoblastoid cell lines, whereas the cytomegalovirus and, more significantly, spleen focus-forming virus (SFFV) promoters mediated the expression of supraphysiological levels of FANCA mRNA. Insertion of the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) or a mutated WPRE into the 3' region of PGK-FANCA LVs significantly increased FANCA mRNA levels. At the protein level, however, all tested vectors conferred, per copy of FANCA, similar and physiological levels of the protein, except SFFV LVs, which again conferred supraphysiological levels of FANCA. In spite of their different activity, all tested vectors mediated a similar phenotypic correction in FA-A lymphoblastoid cell lines and also in hematopoietic progenitors from patients with FA-A. On the basis of the efficacy and safety properties of PGK LVs, a PGK LV carrying FANCA and a mutant WPRE is proposed as an optimized vector for the gene therapy of patients with FA-A.


Irisin relaxes rat thoracic aorta: MEK1/2 signaling pathway, KV channels, SKCa channels, and BKCa channels are involved in irisin-induced vasodilation.
This study investigated the effects of irisin on vascular smooth muscle contractility in rat thoracic aorta, and the hypothesis that mitogen-activated protein kinase kinase (MEK1/2) signaling pathway, voltage-gated potassium (KV) channels, small-conductance calcium-activated potassium (SKCa) channels, and large-conductance calcium-activated potassium (BKCa) channels may have roles in these effects. Isometric contraction-relaxation responses of isolated thoracic aorta rings were measured with an organ bath model. The steady contraction was induced with 10-5 M phenylephrine (PHE), and then the concentration-dependent responses of irisin (10-9-10-6 M) were examined in endothelium-intact and -denuded rat thoracic aortas. Also, the effects of irisin incubations on PHE-mediated contraction and acetylcholine (ACh) - mediated relaxation were studied. Irisin exerted the vasorelaxant effects in both endothelium-intact and -denuded aortic rings at concentrations of 10-8, 10-7, and 10-6 M compared with the control groups (p < 0.001). Besides, pre-incubation of aortic rings with irisin (10 nM, 100 nM, or 1 µM for 30 min) augmented ACh-mediated (10-9-10-5) vasodilation in PHE-precontracted thoracic aorta segments but did not modulate PHE-mediated (10-9-10-5) contraction. In addition, MEK1/2 inhibitor U0126, KV channel blocker XE-991, SKCa channel blocker apamin, and BKCa channel blocker tetraethylammonium (TEA) incubations significantly inhibited the irisin-induced relaxation responses. In conclusion, the first physiological findings were obtained regarding the functional relaxing effects of irisin in rat thoracic aorta. The findings demonstrated that irisin induces relaxation responses in endothelium-intact and (or) endothelium-denuded aortic rings in a concentration-dependent manner. Furthermore, this study is the first to report that irisin-induced relaxation responses are related to the activity of the MEK1/2 pathway, KV channels, and calcium-activated K+ (SKCa and BKCa) channels.


Orthodontic movement of a maxillary incisor through the midpalatal suture: a case report.
Orthodontic space closure is a treatment alternative when a maxillary central incisor is missing. The objective of this report was to present an unusual treatment in which a right maxillary central incisor was moved through the midpalatal suture to replace the absent contralateral tooth. The biologic aspects and clinical appearance of the recontoured lateral and central incisors were analyzed. The position of the examined teeth and the appearance of the surrounding soft tissues were satisfactory; however, the upper midline frenulum deviated to the left. The incisor was successfully moved with no obvious detrimental effects as observed on the final radiographs. In the radiographic and tomographic examinations, the midline suture seemed to have followed the tooth movement. The patient expressed satisfaction with the results. It was concluded that orthodontic movement of the central incisor to replace a missing contralateral tooth is a valid treatment option, and the achievement of an esthetic result requires an interdisciplinary approach, including restorative dentistry and periodontics.


Hepatitis C virus in patients with polyarteritis nodosa. Prevalence in 38 patients.
In order to assess the prevalence of hepatitis C virus (HCV) in polyarteritis nodosa (PN), 38 patients with systemic necrotizing angiitis were retrospectively tested for the presence of anti-HCV antibodies (Ab). Twenty-one patients were hepatitis B virus (HBV) positive, comprising group A, and 17 were HBV negative, comprising group B. Two patients from group A had anti-HCV Ab (2/21: 9.5%). One was treated unsuccessfully with corticosteroids, then with vidarabine and plasma exchanges; HBe/anti-HBe seroconversion was not observed and anti-HCV Ab disappeared 8 months after the onset of PN. The second patient was successfully treated with corticosteroids, then vidarabine and plasma exchanges; he recovered from PN, HBV seroconversion occurred, and the anti HCV Ab remained detectable. These results show that: 1) the prevalence of anti HCV Ab in PN related to HBV is nearly the same (9.5%) as the prevalence of HCV Ab observed in patients with chronic hepatitis related to HBV infection; 2) the course of these two viral infections can be different and the role of HCV as an etiologic factor in PN has not been established.


Office management of diabetes in children part 2: common problems.
A problem-solving approach is used to illustrate principles of managing diabetes mellitus in children. Situations discussed include adjustments for hypo- and hyperglycemia and vigorous activity, and care of the diabetic child who has another illness. The usefulness of referral to a diabetes education centre is emphasized.


Photophosphorylation in isolated maize bundle sheath chloroplasts and cells.
Isolated maize bundle sheath chloroplasts showed substantial rates of noncyclic photophosphorylation. A typical rate of phosphorylation coupled to whole-chain electron transport (methylviologen or ferricyanide as acceptor) was 60 mumol per hour per milligram chlorophyll) with a coupling efficiency (P/e(2)) of 0.6. Partial electron transport reactions driven by photosystem I or II supported phosphorylation with P/e(2) values of 0.2 to 0.3. Thus, two sites of phosphorylation seem to be associated with the photosynthetic chain in much the same way as in spinach chloroplasts.Isolated bundle sheath cells were capable of photosynthetic electron transport with membrane permeant electron carriers (but not with ferricyanide) at rates which were similar to those found in isolated chloroplasts. ATP formation also occurred during electron transport when ADP and phosphate were present in the cell suspension. The rates of photophosphorylation reactions in cells were about 30 to 40% of those found in isolated chloroplasts (maximum rate in cells 80 mumoles ATP per hour per milligram chlorophyll with diaminodurene as electron carrier), with the exception of endogenous photophosphorylation (photophosphorylation without added electron carriers) whose rate was three to four times higher in cells than in chloroplasts. The endogenous photophosphorylation in cells appeared to be coupled to pseudo-cyclic, rather than cyclic, electron transport. It was accompanied by O(2) uptake (when the catalase inhibitor KCN was present), was sensitive to dichlorophenyldimethylurea and methylamine, but was totally insensitive to 20 micromolar antimycin which completely inhibited succinate-supported oxidative phosphorylation in the cells. The implications of these and other phenomena associated with photophosphorylation in bundle sheath cells are discussed.


A 3-min all-out cycling test is sensitive to a change in critical power.
The aim of this investigation was to test the hypothesis that a 3-min all-out cycling test would detect a change in critical power (CP) after a 4-wk interval training intervention. Nine habitually active subjects completed a ramp test, two 3-min all-out tests to establish the end power (EP) and the work done above EP (WEP), and three predicting trials to establish CP and W' using the work-time model (W = CPt + W'). After 12 supervised high-intensity interval training sessions over 4 wk, subjects repeated the testing procedures. The CP increased in all subjects after training (pretraining: 230 +/- 53 W; posttraining: 255 +/- 50 W; t8 = 7.47, P < 0.001), with no statistically significant effect on the W' (pretraining: 17.2 +/- 4.2 kJ; posttraining: 15.5 +/- 3.8 kJ; t8 = 2.03, P = 0.08). The all-out test EP was increased after training from 225 +/- 52 W to 248 +/- 46 W (t8 = 6.26, P < 0.001). The EP and CP estimates before and after training were not different and were highly correlated (pretraining: r = 0.96, P < 0.001; posttraining: r = 0.95, P < 0.001). In addition, the increase in EP was correlated with (r = 0.77, P = 0.016) and not different from (t8 = 0.60, P = 0.57) the increase in CP. There was no change in the WEP from pretraining to posttraining (t8 = 1.89, P = 0.10). The present study shows that the 3-min all-out test closely estimates CP across a wide range of aerobic fitness and is sensitive to training-induced changes in CP.


Lee Silverman Voice Treatment to Improve Speech in Parkinson's Disease: A Systemic Review and Meta-Analysis.
Speech changes occur in the early stages of Parkinson's disease (PD) and cause communication difficulties, leading to social isolation. Lee Silverman voice treatment (LSVT) is a speech therapy approach designed to improve patients' language and voice capabilities. The effectiveness of the LSVT was compared with that of other speech interventions or no treatment to evaluate PD patients with dysarthria. Systematic review with meta-analysis of randomized trials. Data Sources: PubMed, Embase, Cochrane Library, CNKI, and SinoMed library were searched from inception to December 2021 related to PD and LSVT. Abstracts were screened and reviewed against the eligibility criteria (intervention group participants were PD assessed based on LSVT (LSVT Loud) and randomized control). Ten randomized controlled trials were identified on speech symptoms in patients with PD. Compared with the respiratory therapy (RET) exercise, or no training group, a significant improvement was detected in the sound press level (SPL) after immediate treatment during the reading of vowel and rainbow passages and an increase in semitone standard deviation (STSD). Furthermore, the LSVT training significantly increased the participants' scores on unified Parkinson's disease rating scale (UPDRS-III) and speech intelligibility. This meta-analysis demonstrated the efficacy of LSVT in increasing vocal loudness and functional communication among individuals with PD. However, most studies included participants with mild-moderate PD. Thus, additional randomized controlled trials (RCTs) with large sample sizes are needed to validate the efficacy of LSVT in patients with different progressions of PD, including severe PD.


Synthesis of a new fluorescent probe specific for catechols.
[reaction: see text] The synthesis of a new fluorescent probe, specific for the catechol moiety, has been conducted by preparation of alpha,alpha-dibromomalonamides containing an appropriate fluorophore. N,N'-Bis-anthracen-9-ylmethyl-2,2-dibromomalonamide reacted with various catechols in the presence of cesium carbonate to generate highly fluorescent derivatives.


Health visitors' and nurses' role in the 65-year follow-up of an early post-war birth cohort.
This paper describes a national birth cohort study of influences on health, development and ageing processes throughout life, so far to age 65 years. It began as an early post-war study of maternity in England, Wales and Scotland two years before the NHS began, and continued as a follow-up study of a large sample (5362) of those births. The study has influenced scientific and policy thinking by showing the relationships of children's physical and mental development and home background with many aspects of health and life chances throughout their life, including the processes of physical and mental ageing. Health visitors and research nurses have been closely involved in the study's work throughout. Four comparable cohort follow-up studies have since been started in Britain, and a sixth is soon to begin. These national cohort studies provide the opportunity to compare development and health in succeeding generations. Health visitors and nurses have also been involved in these subsequent studies.


[Bioptic. A refractive surgery procedure for correction of high and extreme myopia].
The complete correction of highly or extremely myopic eyes to emmetropia can only be achieved by very few procedures: The combination of implanting phacic intraocular lenses and the use of LASIK (laser in-situ keratomileusis) - Bioptic - makes it possible to achieve this goal to a great extent. The Bioptic procedure was carried out on 17 eyes of 10 patients. Two weeks after corneal dissection with the Hansatom,an implantable phacic lens (STAAR) was introduced into the posterior chamber and 4 weeks later the residual myopia was treated with LASIK combined with the correction of astigmatic errors. The follow-up time was 10.2 (6.7) months. Preoperative average values of the manifest refraction were -16.22 sph (3.86) with 1.40 cyl (1.30) which changed to -3.85 sph (2.73) with -1.50 cyl (0.87) after implantation of an ICL trade mark into the posterior chamber. Visual acuity increased from uncorrected hand motion to 0.13 (0.10) and corrected from 0.53 (0.19) to 0.63 (0.19). The refraction of implanted ICLs trade mark was 14.6 dpt (1.1). Following the LASIK procedure the uncorrected visual acuity improved to 0.68 (0.16) and fully corrected to 0.79 (0.20). The final refraction measured +0.16 sph (0.67) with -0.48 cyl (0.25). The keratectomy depth was 80.63 -m (26.9) and the optical zone showed a horizontal distance of 6.28 mm (0.39). Bioptic is able to correct highly and extremely myopic eyes with the combination of phacic lenses and subsequent LASIK. A concomitant astigmatism can be corrected up to 2.5 dpt simultaneously. With the combination of both procedures,the optical zone can be enlarged. Keeping in mind that phacic lenses reveal a constant refraction after a few days and also that LASIK is refractively safe in low myopia of -4 dpt to -5 dpt, it can be expected that the refractive deviation following the Bioptic procedure is low.


Effect of calcium on phosphorus metabolism in man.
The effect of calcium on phosphorus metabolism was studied in adult males by determining phosphorus and calcium balances during three calcium intakes of approximately 200, 800, and 2000 mg/day. Each of these calcium intakes were given during two intake levels of phosphorus of approximately 800 and 2000 mg/day. In all studies, the addition of different amounts of calcium led to a significant decrease of the urinary phosphorus, a significant increase of the stool phosphorus, and significant improvement of the phosphorus balance irrespective of the phosphorus intake. Only in one study in which the calcium intake was increased from 230 to 831 mg/day during the high phosphorus intake of approximately 2000 mg/day were these changes not significant. During all calcium intakes, the decrease in urinary phosphorus was greater than the increase in stool phosphorus irrespective of the phosphorus intake. The apparent absorption of phosphorus decreased on increasing the calcium intake. The calcium balance was not adversely affected by increasing the phosphorus intake to 2000 mg/day during any of the calcium intakes.


Dermal lymphangiomata of the vulva and laser therapy: a case report and literature review.
Dermal lymphangioma of the vulva is a rare disorder of the lymphatic system. The mainstay of therapy has been vulvectomy. A 65-year-old woman with a remote history of cervical cancer who successfully underwent CO2 laser vaporization for extensive vulva lymphangiomata, and a literature review inclusive of all 28 previously reported cases are described. Ten (35.7%) of these patients had previously received pelvic radiation for cervical cancer, 8 of whom (80%) had also undergone radical hysterectomy. Including the present case, 5 patients, 3 of whom had previously received radiation therapy, have been treated successfully with laser therapy. These data support laser vaporization with retreatment of persistent or recurrent focal disease as the treatment of choice for dermal lymphangiomata. Surgical excision should be reserved for treatment failures. Radical hysterectomy in association with postoperative pelvic radiation therapy appears to be an important, previously unrecognized risk factor for its development.


The natural killer-related receptor for HLA-C expressed on T cells from CD3+ lymphoproliferative disease of granular lymphocytes displays either inhibitory or stimulatory function.
Four patients with lymphoproliferative disease of granular lymphocytes (LDGL) coexpressing CD3 and the natural killer (NK)-related "p58" receptor for HLA-C alleles were studied. These CD3+p58+ LDGLs have been detected among a series of 44 CD3+ LDGLs analyzed. Two patients with LDGL (GI and BA) expressed only the p58 molecule defined by the GL-183 and CH-L monoclonal antibodies (MoAbs), while the cases of patients PU and MA also coexpressed the molecular form identified by EB6 anti-p58 MoAb. Three LDGL cases (GI, MA, and PU) displayed the CD8+4-CD16+ T-cell receptor (TCR)alpha/beta+ phenotype, while one patient (BA) was CD8+4+CD16+ TCRalpha/beta+. Freshly isolated granular lymphocytes (GL) from these cases displayed cytolytic activity in an anti-CD3 MoAb-triggered redirected killing assay against the Fcgamma-receptor+ (Fcgamma-R+) P815 target cell line. Lysis of P815 target cells, triggered by an anti-CD3 or by anti-CD16 MoAb, could be inhibited by the addition of anti-p58 MoAb in three fresh or interleukin (IL)-2-cultured GL tested (GI, MA, and PU). Triggering of cytotoxicity against the HLA-DR+ Fcgamma-R+ Daudi cell line induced by appropriate superantigens could also be inhibited by anti-p58 MoAb in patients PU and GI with LDGL. These data indicate that activation through the CD16, CD3, and TCR molecules can be modulated by p58 receptors in these LDGLs. On the contrary, IL-2-expanded cells of patient BA were induced to lyse P815 target cells by anti-p58 MoAb. In addition, anti-p58 MoAB enhanced anti-CD16 MoAb triggered lysis and did not inhibit activation via CD3. These data indicate that, in this particular patient with LDGL, p58 displays a stimulatory effect on cell triggering, rather than the typical inhibitory effect previously observed in p58+ T-cell clones derived from healthy donors. The anti-p58 MoAb did not induce CA++ mobilization in p58+ LDGLs and in a p58+CD3+ normal T-cell clone equipped with inhibitory p58 molecules, while Ca++ mobilization could be observed in cultured GL from patient BA, which could be activated by anti-58 MoAb. These findings suggest that stimulatory and inhibitory p58 molecules are equipped with different signal transducing properties, thus contributing to a better knowledge of the normal counterpart.


Surgical treatment of arteriovenous malformations in the lateral ventricle.
Ten patients with arteriovenous malformation (AVM) predominantly involving the lateral ventricle were operated upon. All the AVM's were not large, less than 2 cm in diameter. Four AVM's were located in the head of the caudate nucleus; 3 were resected through frontal transcortical (transventricular) approach and 1 was excised through anterior transcallosal approach. Two of the former and the latter gave excellent results. Two AVM's located in the temporal horn and trigon in the dominant hemisphere were excised by middle temporal gyrus approach with excellent results. Four AVM's on the dorsal aspect of the thalamus were removed through posterior transcallosal approach with excellent results in 2 and good ones in 1. The brain incision should be as small as possible to enter the lateral ventricle. Position of the patients is also very important. Exposure to excise the AVM's predominantly located in the lateral ventricle is briefly discussed.


Discovery and mass spectrometric analysis of novel splice-junction peptides using RNA-Seq.
Human proteomic databases required for MS peptide identification are frequently updated and carefully curated, yet are still incomplete because it has been challenging to acquire every protein sequence from the diverse assemblage of proteoforms expressed in every tissue and cell type. In particular, alternative splicing has been shown to be a major source of this cell-specific proteomic variation. Many new alternative splice forms have been detected at the transcript level using next generation sequencing methods, especially RNA-Seq, but it is not known how many of these transcripts are being translated. Leveraging the unprecedented capabilities of next generation sequencing methods, we collected RNA-Seq and proteomics data from the same cell population (Jurkat cells) and created a bioinformatics pipeline that builds customized databases for the discovery of novel splice-junction peptides. Eighty million paired-end Illumina reads and ∼500,000 tandem mass spectra were used to identify 12,873 transcripts (19,320 including isoforms) and 6810 proteins. We developed a bioinformatics workflow to retrieve high-confidence, novel splice junction sequences from the RNA data, translate these sequences into the analogous polypeptide sequence, and create a customized splice junction database for MS searching. Based on the RefSeq gene models, we detected 136,123 annotated and 144,818 unannotated transcript junctions. Of those, 24,834 unannotated junctions passed various quality filters (e.g. minimum read depth) and these entries were translated into 33,589 polypeptide sequences and used for database searching. We discovered 57 splice junction peptides not present in the Uniprot-Trembl proteomic database comprising an array of different splicing events, including skipped exons, alternative donors and acceptors, and noncanonical transcriptional start sites. To our knowledge this is the first example of using sample-specific RNA-Seq data to create a splice-junction database and discover new peptides resulting from alternative splicing.


A global patient outcomes registry: Cochlear paediatric implanted recipient observational study (Cochlear(™) P-IROS).
Currently, there is a paucity of data concerning the long-term outcomes, educational placement and quality of life of children implanted with hearing devices from large and representative samples of the population. To address this concern, a large, prospective, multicentre, multinational patient-outcomes registry for paediatric recipients of implantable hearing devices was developed. The benefits of this registry, its approach and methodology are described. The Cochlear(™) Paediatric Implanted Recipient Observational Study (Cochlear P-IROS) is a prospective international patient-outcomes registry for children who are implanted in routine clinical practice with one or more hearing devices. The study aims to collect data on patient comorbidities, device use, auditory performance, quality of life and health-related utilities, across different types of implantable hearing devices from a range of manufacturers. Patients will be evaluated with a set of standardised and non-standardised questionnaires prior to initial device activation (baseline) and at six-monthly follow-up intervals up to 24 months and annually thereafter. The Cochlear P-IROS utilises a secure web interface to administer electronic case report forms to clinicians and families of implanted children. The web interface is currently available in five languages: English, Japanese, Korean, Mandarin and Russian. The interface also provides printable versions of the case report forms translated into 22 local languages for collection of data prior to entry online; additional languages may be added, as required. Participation in the Cochlear P-IROS registry is investigator-driven and voluntary. To date, the Cochlear P-IROS has recruited implant clinics across Australia, China, India, Indonesia, Turkey and Vietnam. The registry also aims to recruit multiple clinics in Cuba, Israel, Japan, Malaysia, Singapore, South Africa, South Korea and Russia. The use of a registry such as the Cochlear P-IROS will generate valuable data to support research interests of academics and clinicians around the globe. The data generated will be relevant for a wide range of stakeholders including regulators, payers, providers, policy makers, patients and their families, each with a different perspective for the acceptance and adoption of implantable hearing devices for the treatment of hearing loss.


Evaluation of several flow cytometric assays for the analysis of T-cell responses in goats.
Flow cytometry (FCM) provides an alternative to radioactive methods for the analysis of T-cell responses. However, a comparative study of common FCM assays in an outbred ruminant model is lacking, which motivated this work. Goats immunized with the obligate intracellular bacterium Cowdria ruminantium, inactivated and emulsified in oil-based adjuvants, were used as a model to study T-cell recall responses in vitro. FCM-based methods to measure Cowdria-induced lymphoblastogenesis, DNA synthesis, and interleukin-2 receptor (IL-2R) expression by T-cell subsets were compared. IL-2R expression was the most sensitive and reliable method provided that the number of molecules per cell was analyzed and not simply the percentage of positive cells of a given phenotype. Despite high background due to adjuvant and low proliferation, this method could detect antigen-specific activation of immune CD4(+) and CD8(+) T cells. FCM-based measurement of lymphoblastogenesis and DNA synthesis are not the most appropriate methods to analyze T-lymphocyte activation during vaccination of outbred animals. On several occasions, analysis of IL-2R expression was the only assay capable of discriminating between vaccinated and naive animals in this model.


Targets of B lymphocyte antigen receptor signal transduction include the p21ras GTPase-activating protein (GAP) and two GAP-associated proteins.
Cross-linking membrane Ig (mIg) on B cells stimulates tyrosine phosphorylation of proteins involved in signal transduction including the mIg-associated proteins Ig-alpha and Ig-beta, the tyrosine kinases p53/p56lyn, p55blk, p59fyn, and PTK72, phosphatidylinositol 3-kinase, phospholipase C gamma 1 and gamma 2, and the mitogen-activated protein kinase. We now show that the p21ras GTPase-activating protein (GAP) is also a substrate for mIg-activated tyrosine kinases. p21ras is a key regulator of cell growth and GAP may act as both a regulator of p21ras activity and as a downstream effector of p21ras. We found that mIg cross-linking caused a rapid increase in tyrosine phosphorylation of GAP in the immature B cell line WEHI-231, the mature B cell lines BAL 17 and Daudi, and the IgG-bearing B cell line A20. In fibroblasts, tyrosine kinase activation causes GAP to associate with two other tyrosine-phosphorylated proteins, p62 and p190, which have homologies to an RNA-binding protein and a transcriptional repressor, respectively. Similarly, mlg cross-linking induced the association of GAP with a 62-kDa tyrosine-phosphorylated protein in BAL 17, WEHI-231, and Daudi cells. Anti-Ig treatment also increased the amount of a 190-kDa tyrosine-phosphorylated protein associated with GAP in WEHI-231 and Daudi cells. After separation by SDS-PAGE and transfer to nitrocellulose, the tyrosine-phosphorylated p62 and p190 present in anti-GAP immunoprecipitates from B cells were capable of binding radiolabeled recombinant GAP, as previously reported for the GAP-associated p62 and p190 from fibroblasts. The amount of p62 that could be detected in this way after immunoprecipitation with antiphosphotyrosine antibodies was much greater from anti-IgM-treated BAL 17 cells than from unstimulated BAL 17 cells. This probably reflects anti-Ig-induced tyrosine phosphorylation of p62. In any case, GAP, p62, and/or p190 may be involved in signal transduction by mIg in B cells.


A review of echinoderm oogenesis.
This review of the anatomical, histological, biochemical, and molecular biological literature on echinoderm oogenesis includes the entire developmental history of oocytes; from their inception to the time they become ova. This is done from a comparative perspective, with reference to members of the five extant echinoderm classes; crinoids, holothurians, asteroids, ophiuroids, and echinoids. I describe the anatomy and fine structure of the echinoderm ovary, with emphasis on both the cellular relationships of the germ line cells to the somatic cells of the inner epithelium, and on the neuromuscular systems. I review the literature on the growth of oogonia into fully formed oocytes, including the process of vitellogenesis, presenting an ultrastructural analysis of the organelles and extracellular structures found in fully formed echinoderm oocytes. Echinoderm oocyte maturation is reviewed and a description of the ultrastructural, biochemical and molecular biological changes thought to occur during this process is presented. Finally, I discuss oocyte ovulation, the severing of cellular connections between the oocyte and its surrounding somatic epithelial cells.


Hand and wrist research productivity in journals with high impact factors: a 20 year analysis.
Bibliometric analyses, which study trends in research productivity, have not previously been applied to hand and wrist research. This study analyses temporal and geographic trends in hand and wrist research from 1988 to 2007. Original research articles were collected from seven English language journals selected on the basis of impact factor. Research production and quality (level of evidence) were determined by country and global region. Linear regression analysis was used to investigate trends. No significant increase in research volume was observed, but journal impact factors have risen significantly since 1988. Western Europe contributed significantly more high-quality (Level I and II) studies than the United States. Research contributions show a geographical distribution concentrated in the US and Western Europe, but considerable changes in this distribution have occurred. From 1988 to 2007, there was a relative increase in research production from Europe, Latin America and Asia, and a relative decline from the US.


Acute leukemia and related entities. Impact of new technology.
Twenty-seven cases of acute leukemia and related entities were evaluated by morphologic examination, cytochemical study, terminal deoxynucleotidyltransferase study, immunophenotyping, cytogenetic analysis, ultrastructural cytochemical study, and gene rearrangement analysis to determine the impact on the determination of the French-American-British (FAB) classification and the definitive diagnosis. The definitive diagnosis contained prognostic, diagnostic, and treatment information beyond the FAB classification that affected the disease course and patient management. All diagnostic variables were evaluated in each case and were labeled essential, ambivalent, supportive, or noncontributory. Except for gene rearrangement analysis, all variables we studied contributed essential data to establish the definitive diagnosis. Ambivalent findings were rare but could be explained with the knowledge of the total data. All variables, except cytochemical study, whose results were almost always essential, contributed supportive data. Noncontributory data only occurred with cytogenetic analysis in cases that demonstrated normal karyotypes. The FAB classification was established in 20 (74%) of the cases by use of morphologic examination, cytochemical study, and terminal deoxynucleotidyltransferase study. With use of the same variables, however, the definitive diagnosis, whose determination required all data, was established in only 15 (55.5%) of the cases. The addition of immunophenotyping increased the definitive diagnosis to 25 (92.5%) of the cases. The use of ultrastructural myeloperoxidase and platelet peroxidase analysis enabled us to definitively diagnose the remaining two cases (27 cases [100%]). Cytogenetic analysis revealed four cases in which essential information was added to the diagnosis. However, because the cytogenetic information usually was not immediately available, the result did not affect the immediate diagnosis or treatment. Surprisingly, the gene rearrangement studies did not yield essential data in any case and in a few cases contributed ambivalent data. This finding should not exclude gene rearrangement analysis in selected cases; however, the data should always be interpreted in light of all clinical and laboratory findings. This study clearly demonstrates the importance of a multifaceted approach to the understanding of the acute leukemias and related entities and shows the impact of newer technologies on reaching a definitive diagnosis.


Electron-nuclear energy sharing in above-threshold multiphoton dissociative ionization of H2.
We report experimental observation of the energy sharing between electron and nuclei in above-threshold multiphoton dissociative ionization of H2 by strong laser fields. The absorbed photon energy is shared between the ejected electron and nuclei in a correlated fashion, resulting in multiple diagonal lines in their joint energy spectrum governed by the energy conservation of all fragment particles.


Effect of Nutritional Habits on the Glycemic Response to Different Carbohydrate Diet in Children with Type 1 Diabetes Mellitus.
Unhealthy eating habits are associated with obesity, metabolic syndrome, and increased insulin resistance in young patients with type 1 diabetes mellitus (T1DM), and may impact the possible benefit from dietary interventions on glycaemic control. This study determines how nutritional patterns influence the quality of dietary intervention with a 30% or 50% carbohydrate diet in terms of glycaemic control measured with continuous glucose monitoring (CGM). Eating habits were obtained with a frequency-of-consumption questionnaire (FFQ-6) before the diet assessment. Altogether, we collected CGM and FFQ-6 data from 30 children (16 boys and 14 girls aged 10-17 years) with T1DM subjected to two consecutive 3-day nutritional plans. From these, 23 patients met the CGM data quality criteria for further analysis. Furthermore, high accuracy achieved in training (95.65%) and V-fold cross-validation (81.67%) suggest a significant impact of food habits in response to introduced nutritional changes. Patients who consumed more vegetables or grains (>4 times per day), more wheat products (>once per day), fewer fats (<1.5 times per day), and ranked fruit juice as the most common selection in the drinks category achieved glycaemic control more often after the introduction of a 30% carbohydrate diet, as opposed to those with different dietary patterns, whose glycaemic control was negatively impacted after switching to this diet. Additionally, the 50% carbohydrate diet was safe for all patients in the context of glycaemic control.


Bioprospecting White-Rot Basidiomycete Irpex lacteus for Improved Extraction of Lignocellulose-Degrading Enzymes and Their Further Application.
Lignocellulosic biomass can be used as a source for energy, fuel and valuable chemical production. From all available technologies, biological approaches have been recognized as the most environmentally friendly and sustainable ones. At the same time, high conversion costs, low efficiency and environmental issues still hinder the introduction of biological processes into industrial scale manufacturing. The aim of this study was to determine the most suitable enzyme cocktail recovery conditions from a biomass-fungal culture of the white-rot basidiomycete Irpex lacteus. Subsequent evaluation of the overall enzyme cocktail efficiency to release fermentable carbohydrates from biomass showed that prolonged fungal cultivation decreases the quality of the produced enzyme cocktail. At the same time, introduction of ultrasound pre-treatment during enzyme extraction improved the recovered enzyme cocktail efficiency in converting biomass to fermentable sugars, yielding up to 0.25 g of fermentable sugar per g dry hay biomass and up to 0.11 g per g dried straw or microalgae substrates. The results demonstrated that the production of lignocellulose-degrading enzymes from fungi is more sensitive than previously described, especially in terms of fungal growth, culture sterility and incubation conditions.


Diabetes, obesity, metabolism, and SARS-CoV-2 infection: the end of the beginning.
The increased prevalence of obesity, diabetes, and cardiovascular risk factors in people hospitalized with severe COVID-19 illness has engendered considerable interest in the metabolic aspects of SARS-CoV-2-induced pathophysiology. Here, I update concepts informing how metabolic disorders and their co-morbidities modify the susceptibility to, natural history, and potential treatment of SARS-CoV-2 infection, with a focus on human biology. New data informing genetic predisposition, epidemiology, immune responses, disease severity, and therapy of COVID-19 in people with obesity and diabetes are highlighted. The emerging relationships of metabolic disorders to viral-induced immune responses and viral persistence, and the putative importance of adipose and islet ACE2 expression, glycemic control, cholesterol metabolism, and glucose- and lipid-lowering drugs is reviewed, with attention to controversies and unresolved questions. Rapid progress in these areas informs our growing understanding of SARS-CoV-2 infection in people with diabetes and obesity, while refining the therapeutic strategies and research priorities in this vulnerable population.


[Results of therapy in Wilms' tumor].
Two hundred seventeen patients (aged under 14) with histologically confirmed Wilms tumor were treated and followed up in 1965-1995. Until 1976 this condition was treated according to the national standard procedures of the time. The SIOP program approach has been introduced ever since. In a study group of 154 cases treated at the Institute's Clinic alone, the actuarial 20-year survival was 63%. It rose to 72% whenever the SIOP protocol was strictly observed.


Bone changes associated with intraosseous hypertension in the caprine tibia.
We investigated the effects of increased intraosseous pressure on new-bone formation in the proximal metaphysis of the caprine tibia. Intraosseous hypertension was produced by obstruction of venous outflow by ligation of the popliteal vein draining the proximal aspect of the tibia and occlusion of the medullary space with bone cement (groups 1 and 2). After the obstruction of venous outflow (day 0), the intraosseous pressure measured at the proximal tibial metaphysis increased significantly from a mean of 15.5 millimeters of mercury before the obstruction to a mean of 28.7 millimeters of mercury in groups 1 and 2. In group 1, obstruction of venous outflow was combined with intraosseous infusion of autogenous whole blood under pressure to maintain the intraosseous pressure between thirty and forty-five millimeters of mercury during days 0 through 5. The time for venous drainage was still prolonged and intraosseous pressures were still increased on days 5 and 10 (means, 26.8 and 26.2 millimeters of mercury, respectively) in groups 1 and 2. The intraosseous hypertension produced in group 1 was associated with a significant increase in periosteal (138 per cent), endocortical (369 per cent), and cancellous new-bone formation (889 per cent) at the tibial metaphysis compared with control values. Osseous necrosis within the metaphysis was not observed.


Logical analysis of survival data: prognostic survival models by detecting high-degree interactions in right-censored data.
Survival analysis involves predicting the time to event for patients in a dataset, based on a set of recorded attributes. In this study we focus on right-censored survival problems. Detecting high-degree interactions for the estimation of survival probability is a challenging problem in survival analysis from the statistical perspective. We propose a new methodology, Logical Analysis of Survival Data (LASD), to identify interactions between variables (survival patterns) without any prior hypotheses. Using these set of patterns, we predict survival distributions for each observation. To evaluate LASD we select two publicly available datasets: a lung adenocarcinoma dataset (gene-expression pro.les) and the other a breast cancer dataset (clinical pro.les). The performance of LASD when compared with survival decision trees improves the cross-validation accuracy by 18% for the gene-expression dataset, and by 2% for the clinical dataset. Executable codes will be provided upon request.


The reliability of ERP components in the auditory oddball paradigm.
Nineteen adolescents (average age 15 years, 3 months) were tested and retested using a standard 40 target, auditory oddball ERP paradigm across an interval of 1 year, 10 months to determine reliability of the ERP components, both in terms of intersubject stability and score agreement and in terms of trait (between-session reliability) versus state (within-session reliability). Significant trait stability was found for the N100, P200, and P300 latencies (r = .48, .51, and .74, respectively), and for P300 amplitude (r = .62), supporting the P300 as a reliable measure, with the stability required for group research but not necessarily for clinical applications. Discussion and examples illustrate the application of reliability information to the planning and evaluation of ERP paradigms.


Alcohol problems among residents in old age homes in the city of Mannheim, Germany.
This study aims to determine the prevalence of alcohol problems among residents in old age homes, its demographic and clinical features, and its association with the risk of falling. All residents (n = 1922) living in 20 randomly selected residential and nursing homes in the city of Mannheim, Germany, were included. Based on routine documentation, details of their sociodemographic features, medical diagnoses made upon admission, and current medication were compiled. The home staff filled out for each resident a standardised assessment sheet on activities of daily living-impairment (Barthel Index), behaviour problems, alcohol consumption, and frequency of falls. According to the diagnoses of the primary care physicians, 7.4% of the residents had mental and behavioural disorders due to alcohol (ICD-10: F10). Rates were particularly high among men, and younger and single or divorced residents. A high percentage of those with a diagnosis of alcohol abuse/dependence (41.1%) were transferred from mental hospitals. Home staff reported current alcohol abuse/dependence among 3.4% of all residents. The risk of falling was significantly elevated (Odds ratio: 2.65; p<0.01) among those with current alcohol problems. The results corroborate the findings from other studies wherein residents of old age homes constitute a group at risk of alcohol abuse and dependence. Alcohol problems were more the cause for, rather than the consequence of, home admission.


Acoustic Analysis of PD Speech.
According to the U.S. National Institutes of Health, approximately 500,000 Americans have Parkinson's disease (PD), with roughly another 50,000 receiving new diagnoses each year. 70%-90% of these people also have the hypokinetic dysarthria associated with PD. Deep brain stimulation (DBS) substantially relieves motor symptoms in advanced-stage patients for whom medication produces disabling dyskinesias. This study investigated speech changes as a result of DBS settings chosen to maximize motor performance. The speech of 10 PD patients and 12 normal controls was analyzed for syllable rate and variability, syllable length patterning, vowel fraction, voice-onset time variability, and spirantization. These were normalized by the controls' standard deviation to represent distance from normal and combined into a composite measure. Results show that DBS settings relieving motor symptoms can improve speech, making it up to three standard deviations closer to normal. However, the clinically motivated settings evaluated here show greater capacity to impair, rather than improve, speech. A feedback device developed from these findings could be useful to clinicians adjusting DBS parameters, as a means for ensuring they do not unwittingly choose DBS settings which impair patients' communication.


Silvery hair syndrome in two cousins: Chediak-Higashi syndrome vs Griscelli syndrome, with rare associations.
Silvery hair is a rare clinical manifestation which is a common presentation in a group of rare syndromes which usually present in the pediatric age group together termed as "silvery hair syndrome," consisting of Chediak-Higashi syndrome (CHS), Griscelli syndrome (GS), and Elejalde disease. CHS is a rare autosomal recessive disorder. It is characterized by mild pigment dilution (partial oculocutaneous albinism), silvery blond hair, severe phagocytic immunodeficiency, bleeding tendencies, recurrent pyogenic infections, progressive sensory or motor neurological defects. GS is also a rare autosomal recessive disorder characterized by reduced skin pigmentation, often regarded as partial albinism and silvery grey hair combined with immunodeficiency. To make correct diagnosis and to differentiate between CHS and GS, it requires light microscopic examination of skin and hair shafts, immunological and peripheral blood smear evaluation. They have been reported to be associated with some common clinical association as a part of the syndrome due to pigmentary delusion, neurological dysfunction, and severe life-threatening infections due to neutrophil phagocytosis dysfunction. There are reports of few rare associations and varied presentations and variable mean survival age. We report two cases with common presentation of silvery hair but varied systemic and clinical manifestations and survival in two cousin brothers from the same family.


Comparative transcriptome analysis reveals novel roles of the Ras and cyclic AMP signaling pathways in environmental stress response and antifungal drug sensitivity in Cryptococcus neoformans.
The cyclic AMP (cAMP) pathway plays a central role in the growth, differentiation, and virulence of pathogenic fungi, including Cryptococcus neoformans. Three upstream signaling regulators of adenylyl cyclase (Cac1), Ras, Aca1, and Gpa1, have been demonstrated to control the cAMP pathway in C. neoformans, but their functional relationship remains elusive. We performed a genome-wide transcriptome analysis with a DNA microarray using the ras1Delta, gpa1Delta, cac1Delta, aca1Delta, and pka1Delta pka2Delta mutants. The aca1Delta, gpa1Delta, cac1Delta, and pka1Delta pka2Delta mutants displayed similar transcriptome patterns, whereas the ras1Delta mutant exhibited transcriptome patterns distinct from those of the wild type and the cAMP mutants. Interestingly, a number of environmental stress response genes are modulated differentially in the ras1Delta and cAMP mutants. In fact, the Ras signaling pathway was found to be involved in osmotic and genotoxic stress responses and the maintenance of cell wall integrity via the Cdc24-dependent signaling pathway. Notably, the Ras and cAMP mutants exhibited hypersensitivity to a polyene drug, amphotericin B, without showing effects on ergosterol biosynthesis, which suggested a novel method of antifungal combination therapy. Among the cAMP-dependent gene products that we characterized, two small heat shock proteins, Hsp12 and Hsp122, were found to be involved in the polyene antifungal drug susceptibility of C. neoformans.


Treatment complications of rheumatoid arthritis with gold, hydroxychloroquine, D-penicillamine, and levamisole.
One hundred and twenty-five patients with active rheumatoid arthritis unresponsive to nonsteroidal antiinflammatory drugs were treated at the same center with 156 courses of either hydroxychloroquine (43), gold (29), D-penicillamine (40), or levamisole (44). Life table analysis was used to compare the risks of developing various side effects with treatment termination being the endpoint instead of death. Patients treated with levamisole had the highest risk of developing a complication (67%) and antimalarials the lowest (30%). In terms of long term acceptability, hydroxychloroquine showed fewer complications, gold and D-penicillamine were similar with rash and proteinuria being the main difficulties; however, levamisole caused the most frequent terminations mainly due to rash and leukopenia.


Managing myocarditis in a patient with newly diagnosed dermatomyositis.
A woman in her 20s presented with chest pain, dyspnoea, arthralgia, muscle weakness and skin discolouration. She was diagnosed with dermatomyositis. During her admission, she developed pleuritic chest pain and shortness of breath accompanied by a significant troponin I rise. Her echocardiogram showed a hyperdynamic left ventricle with a trivial pericardial effusion; there were no regional wall motion abnormalities. Gadolinium-diethylenetriaminepantaacetic-enhanced cardiac MRI showed extensive myocarditis. She was started on corticosteroids and azathioprine which led to an improvement of symptoms and biochemical markers.


Effect of copper-zinc superoxide dismutase on endothelium-dependent vasodilation in patients with essential hypertension.
Patients with essential hypertension have abnormal endothelium-dependent vasodilation related to decreased nitric oxide activity. The specific mechanism responsible for this abnormality is unknown. Recent studies in hypertensive animals have suggested an augmented destruction of nitric oxide by superoxide anions. Therefore, in the present study we aimed to investigate whether this mechanism is responsible for the abnormal vasodilator function of hypertensive patients. To this end, we studied the vascular responses to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct smooth muscle dilator) before and after combined administration of copper-zinc superoxide dismutase (a scavenger of superoxide anions with poor intracellular penetrance; 6000 U/min) in 20 healthy control subjects (11 men and 9 women; aged 50 +/- 6 years) and 20 hypertensive patients (13 men and 7 women; aged 51 +/- 9 years). Drugs were infused into the brachial artery, and the response of the forearm vasculature was measured by plethysmography. The vasodilator response to acetylcholine was significantly blunted in hypertensive patients compared with control subjects (maximal flow: 8.2 +/- 4 versus 12.7 +/- 3 mL/min per 100 mL; P < .02); however, no difference was observed in the response to sodium nitroprusside (8.1 +/- 4 versus 9.5 +/- 3 mL/min per 100 mL). In healthy control subjects superoxide dismutase infusion did not modify the vasodilator response to acetylcholine (maximal flow: 12.7 +/- 3 before versus 12.1 +/- 3 after superoxide dismutase). Similarly, in hypertensive patients superoxide dismutase infusion did not alter the response to acetylcholine (maximal flow: 8.2 +/- 4 versus 7.7 +/- 4).(ABSTRACT TRUNCATED AT 250 WORDS)


Managing data quality for a drug safety surveillance system.
The objective of this study is to present a data quality assurance program for disparate data sources loaded into a Common Data Model, highlight data quality issues identified and resolutions implemented. The Observational Medical Outcomes Partnership is conducting methodological research to develop a system to monitor drug safety. Standard processes and tools are needed to ensure continuous data quality across a network of disparate databases, and to ensure that procedures used to extract-transform-load (ETL) processes maintain data integrity. Currently, there is no consensus or standard approach to evaluate the quality of the source data, or ETL procedures. We propose a framework for a comprehensive process to ensure data quality throughout the steps used to process and analyze the data. The approach used to manage data anomalies includes: (1) characterization of data sources; (2) detection of data anomalies; (3) determining the cause of data anomalies; and (4) remediation. Data anomalies included incomplete raw dataset: no race or year of birth recorded. Implausible data: year of birth exceeding current year, observation period end date precedes start date, suspicious data frequencies and proportions outside normal range. Examples of errors found in the ETL process were zip codes incorrectly loaded, drug quantities rounded, drug exposure length incorrectly calculated, and condition length incorrectly programmed. Complete and reliable observational data are difficult to obtain, data quality assurance processes need to be continuous as data is regularly updated; consequently, processes to assess data quality should be ongoing and transparent.


Effect of arylhydroxylamine metabolites of sulfamethoxazole and dapsone on stress signal expression in human keratinocytes.
The initiation of an immune response to small molecules is believed to require the release of stress/danger signals that activate resident dendritic cells, presumably secondary to the formation of reactive metabolites. We hypothesized that exposure to arylhydroxylamine metabolites of dapsone and sulfamethoxazole lead to the expression/release of numerous stress signals in the skin. To test this hypothesis, we examined the effect of these metabolites on the expression of selected heat shock proteins, uric acid, cytokines, adhesion molecules, and costimulatory molecules in normal human epidermal keratinocytes (NHEKs). NHEKs showed a time-dependent up-regulation of heat shock protein 70 and translocation of heat shock protein 27 when exposed to the arylhydroxylamine metabolites. In addition, the secretion of several proinflammatory cytokines was increased upon incubation of these cells with metabolite. In contrast, the uric acid concentration was not altered. Moreover, intercellular adhesion molecule-1, CD80, and CD86 expressions did not change when NHEKs were exposed to these reactive metabolites. Our data suggest that NHEKs selectively up-regulate certain danger signals when exposed to arylhydroxylamine metabolites. These signals may subsequently activate dendritic cells and initiate an immune response within skin.


Hypomyelinating Leukodystrophy 7 (HLD7)-Associated Mutation of POLR3A Is Related to Defective Oligodendroglial Cell Differentiation, Which Is Ameliorated by Ibuprofen.
Hypomyelinating leukodystrophy 7 (HLD7) is an autosomal recessive oligodendroglial cell-related myelin disease, which is associated with some nucleotide mutations of the RNA polymerase 3 subunit a (polr3a) gene. POLR3A is composed of the catalytic core of RNA polymerase III synthesizing non-coding RNAs, such as rRNA and tRNA. Here, we show that an HLD7-associated nonsense mutation of Arg140-to-Ter (R140X) primarily localizes POLR3A proteins as protein aggregates into lysosomes in mouse oligodendroglial FBD-102b cells, whereas the wild type proteins are not localized in lysosomes. Expression of the R140X mutant proteins, but not the wild type proteins, in cells decreased signaling through the mechanistic target of rapamycin (mTOR), controlling signal transduction around lysosomes. While cells harboring the wild type constructs exhibited phenotypes with widespread membranes with myelin marker protein expression following the induction of differentiation, cells harboring the R140X mutant constructs did not exhibit them. Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), which is also known as an mTOR signaling activator, ameliorated defects in differentiation with myelin marker protein expression and the related signaling in cells harboring the R140X mutant constructs. Collectively, HLD7-associated POLR3A mutant proteins are localized in lysosomes where they decrease mTOR signaling, inhibiting cell morphological differentiation. Importantly, ibuprofen reverses undifferentiated phenotypes. These findings may reveal some of the pathological mechanisms underlying HLD7 and their amelioration at the molecular and cellular levels.


Survivorship Care Practices and Confidence of Oncology Nurses in Singapore: A Cross-Sectional Study.
Introduction: Cancer survivorship care is challenging because little is known about delivering comprehensive and coordinated survivorship care practices (SCP) to patients. The purpose of this study is to examine oncology nurses' perceptions of responsibilities of SCP, confidence levels of SCP, and factors that influence provisions of SCP. Method: A descriptive cross-sectional study was conducted using the Cancer Professional Questionnaire. Analysis was conducted using independent t-test and analysis of variance to examine the differences between variables. Results: Nurses (n = 147) agreed that it was their responsibilities to provide SCP, but the majority lacked the confidence to do so. Significant differences were found in the confidence levels of nurses with different education attainments (p = .004). A lack of time and educational resources were factors impeding SCP. Discussion: Organizational interventions and education programs are needed to ensure that oncology nurses are confident in providing culturally congruent survivorship care in a multicultural country such as Singapore.


Impairment of functional integration of the default mode network correlates with cognitive outcome at three months after stroke.
Resting-state studies conducted with stroke patients are scarce. The study of brain activity and connectivity at rest provides a unique opportunity for the investigation of brain rewiring after stroke and plasticity changes. This study sought to identify dynamic changes in the functional organization of the default mode network (DMN) of stroke patients at three months after stroke. Eleven patients (eight male and three female; age range: 48-72) with right cortical and subcortical ischemic infarctions and 17 controls (eleven males and six females; age range: 57-69) were assessed by neurological and neuropsychological examinations and scanned with resting-state functional magnetic ressonance imaging. First, we explored group differences in functional activity within the DMN by means of probabilistic independent component analysis followed by a dual regression approach. Second, we estimated functional connectivity between 11 DMN nodes both locally by means of seed-based connectivity analysis, as well as globally by means of graph-computation analysis. We found that patients had greater DMN activity in the left precuneus and the left anterior cingulate gyrus when compared with healthy controls (P < 0.05 family-wise error corrected). Seed-based connectivity analysis showed that stroke patients had significant impairment (P = 0.014; threshold = 2.00) in the connectivity between the following five DMN nodes: left superior frontal gyrus (lSFG) and posterior cingulate cortex (t = 2.01); left parahippocampal gyrus and right superior frontal gyrus (t = 2.11); left parahippocampal gyrus and lSFG (t = 2.39); right parietal and lSFG (t = 2.29). Finally, mean path length obtained from graph-computation analysis showed positive correlations with semantic fluency test (r(s) = 0.454; P = 0.023), phonetic fluency test (r(s) = 0.523; P = 0.007) and the mini mental state examination (r(s) = 0.528; P = 0.007). In conclusion, the ability to regulate activity of the DMN appears to be a central part of normal brain function in stroke patients. Our study expands the understanding of the changes occurring in the brain after stroke providing a new avenue for investigating lesion-induced network plasticity.


MiR-125a-3p-KLF15-BCAA Regulates the Skeletal Muscle Branched-Chain Amino Acid Metabolism in Nile Tilapia (Oreochromis niloticus) During Starvation.
The branched-chain amino acids (BCAAs) play a key role in the energy metabolism of the muscle tissue and the Krüppel-like factor 15 (KLF15) as a transcription factor, which is a key regulator of BCAA metabolism in the skeletal muscle. This study assessed the effect of starvation for 0, 3, 7, and 15 days on BCAA metabolism in the skeletal muscle of Nile tilapia. The results showed that the expression of KLF15 showed a trend of increasing first and then decreasing during starvation, as well as the expression and activity of branched-chain aminotransferase 2 (BCAT2) and alanine aminotransferase (ALT). On the other hand, the content of BCAA was at first decreased and then upregulated, and it reached the lowest level after starvation for 3 days. In addition, through dual-luciferase reporter assay and injection experiments, it was found that KLF15 is the target gene of miR-125a-3p, which further verified that miR-125a-3p can regulate the BCAA metabolism by targeting KLF15 in the skeletal muscle. Thus, our work investigated the possible mechanisms of BCAA metabolism adapting to nutritional deficiency in the skeletal muscle of Nile tilapia and illustrated the regulation of BCAA metabolism through the miR-125a-3p-KLF15-BCAA pathway in the skeletal muscle.


Period-amplitude analysis and power spectral analysis: a comparison based on all-night sleep EEG recordings.
Both period-amplitude analysis (PAA) and power spectral analysis (PSA) were performed on all-night human sleep EEG recordings obtained from 11 subjects. The comparison of the two methods was based on the PAA variables time in band (a wave incidence measure) and rectified amplitude, and on the PSA variables spectral power density and spectral amplitude (the square root of power). The mean time course of these variables was determined for the first 4 nonREM-REM sleep cycles. Spectral power density and spectral amplitude in the delta range were high in nonREM sleep and low in REM sleep, and showed a declining trend over consecutive nonREM sleep episodes. In the frequency range below 2 Hz, rectified amplitude was highly correlated with both time in band and spectral amplitude, and there was no evidence for a dissociation between wave amplitude and wave incidence measures. However, in frequencies above 2 Hz, the modulation of time in band was a mirror image of that below 2 Hz. This result does not reflect a property of the data, but is inherent to the methodology applied. The reversal point of modulation was merely shifted when the high-pass filter settings were changed. It is concluded that band-pass filtering is necessary prior to PAA even for the analysis of the lowest frequency range, and that the indiscriminate use of PAA may give rise to spurious results.


Alzheimer's Disease Protein Relevance Analysis Using Human and Mouse Model Proteomics Data.
The principles governing genotype-phenotype relationships are still emerging(1-3), and detailed translational as well as transcriptomic information is required to understand complex phenotypes, such as the pathogenesis of Alzheimer's disease. For this reason, the proteomics of Alzheimer disease (AD) continues to be studied extensively. Although comparisons between data obtained from humans and mouse models have been reported, approaches that specifically address the between-species statistical comparisons are understudied. Our study investigated the performance of two statistical methods for identification of proteins and biological pathways associated with Alzheimer's disease for cross-species comparisons, taking specific data analysis challenges into account, including collinearity, dimensionality reduction and cross-species protein matching. We used a human dataset from a well-characterized cohort followed for over 22 years with proteomic data available. For the mouse model, we generated proteomic data from whole brains of CVN-AD and matching control mouse models. We used these analyses to determine the reliability of a mouse model to forecast significant proteomic-based pathological changes in the brain that may mimic pathology in human Alzheimer's disease. Compared with LASSO regression, partial least squares discriminant analysis provided better statistical performance for the proteomics analysis. The major biological finding of the study was that extracellular matrix proteins and integrin-related pathways were dysregulated in both the human and mouse data. This approach may help inform the development of mouse models that are more relevant to the study of human late-onset Alzheimer's disease.


Fractional reactive extraction for symmetrical separation of 4-nitro-D,L-phenylalanine in centrifugal contactor separators: experiments and modeling.
The enantioselective liquid-liquid extraction of 4-nitro-D,L-phenylalanine (D,L-Nphy) using PdCl2 {(s)-BINAP} as extractant in dichloroethane was studied experimentally in a countercurrent cascade of 10 centrifugal contactor separators (CCSs) at 5°C, involving flow ratio, extractant concentration, and Cl(-) concentration. The steady-state enantiomeric excess (ee) in both stream exits was 90.86% at a 93.29% yield. The predicted value was modeled using an equilibrium stage approach. The correlation between model and experiment was satisfactory. The model was applied to optimize the production of both enantiomers in >97% ee and >99% ee. 14 stages and 16 stages are required for 97% ee and 99% ee for both enantiomers, respectively.


Zebrafish modeling reveals that SPINT1 regulates the aggressiveness of skin cutaneous melanoma and its crosstalk with tumor immune microenvironment.
Skin cutaneous melanoma (SKCM) is the most lethal form of skin cancer and while incidence rates are declining for most cancers, they have been steadily rising for SKCM. Serine protease inhibitor, kunitz-type, 1 (SPINT1) is a type II transmembrane serine protease inhibitor that has been shown to be involved in the development of several types of cancer, such as squamous cell carcinoma and colorectal cancer. We used the unique advantages of the zebrafish to model the impact of Spint1a deficiency in early transformation, progression and metastatic invasion of SKCM together with in silico analysis of the occurrence and relevance of SPINT1 genetic alterations of the SKCM TCGA cohort. We report here a high prevalence of SPINT1 genetic alterations in SKCM patients and their association with altered tumor immune microenvironment and poor patient survival. The zebrafish model reveals that Spint1a deficiency facilitates oncogenic transformation, regulates the tumor immune microenvironment crosstalk, accelerates the onset of SKCM and promotes metastatic invasion. Notably, Spint1a deficiency is required at both cell autonomous and non-autonomous levels to enhance invasiveness of SKCM. These results reveal a novel therapeutic target for SKCM.


[The longitudinal development of smoking behavior in men and women between 13 and 27 years and the relationship with biological risk factors for cardiovascular diseases].
To describe the longitudinal development of smoking behaviour from adolescence (age 13 years) into young adulthood (age 27 years) and to analyse the longitudinal relationship between smoking behaviour and biological risk factors for cardiovascular disease. Longitudinal. Amsterdam school children. This study was carried out as part of the Amsterdam Growth and Health Study, an observational longitudinal study. Six measurements were carried out over a period of 15 years in 84 males and 98 females, and included a questionnaire regarding smoking behaviour and blood analysis for cholesterol parameters. Tracking analysis and generalized estimating equations analysis were used. Both the percentage of smokers and the amount of tobacco smoked by smokers increased until the age of 21 years. After that smoking behaviour remained more or less stable in males and decreased slightly in females (period effect). Between 16 and 21 years half the number of persons tried to stop smoking but failed to succeed. The development of smoking behaviour appeared to be related to low systolic blood pressure and to development of a negative risk profile regarding hypercholesterolaemia (i.e. low high-density lipoprotein (HDL) cholesterol and high ratio of total cholesterol and HDL cholesterol). There was no relationship between smoking and the amount of subcutaneous fat.


Dietary Fiber Contents and Its Fermentability In Vitro of Pleurotus ostreatus cv. Florida Mycelia (Agaricomycetes).
Oyster mushrooms (Pleurotus spp.) constitute a substantial resource for functional food, as they are commercially cultivated worldwide and assumed to contain beneficial fiber. The objective of this study was to characterize and analyze the mycelia of Pleurotus ostreatus cv. Florida for its nutrient composition, total dietary fiber, insoluble dietary fiber, soluble dietary fiber content, and fermentability in vitro. Findings showed the mycelia had a moisture content of 18%, ash 12%, protein 5%, fat 0.1%, and carbohydrates 61%. Results also revealed that mycelia are an excellent source of dietary fiber (55%) containing high amounts of insoluble (22%) and soluble (33%) fiber. The mycelia also produced significant amounts of short chain fatty acids after fermentation at in vitro simulating conditions in the colon: acetate (1.92 mg/g), propionate (0.89 mg/g), and butyrate (0.31 mg/g). These results indicated that the mycelia of P. ostreatus cv. Florida are promising sources of dietary fiber.


Using the Agitated Behavior Scale to Evaluate Restlessness/Agitation Following Traumatic Brain InjuryA Case Example.
Restlessness and agitation following traumatic brain injury are potential barriers to successful rehabilitation. Although there are several ways to address the problem, including environmental management, physical restraint, and medication, the type of treatment which would be most appropriate under particular circumstances has not been established. Existing treatment studies often suffer from an emphasis on anecdotal information rather than measurement of restlessness/agitation. Use of the Agitated Behavior Scale would help remedy this situation by allowing more consistent decisions about beginning and altering treatment and providing a measurement device to clarify research results, particularly with respect to the use of medications.


Effects of topical 0.5% tropicamide on intraocular pressure in normal cats.
The objective of the study was to determine the effect of topical 0.5% tropicamide on intraocular pressure (IOP) in normotensive feline eyes. IOP was measured bilaterally in 70 clinically healthy cats and gonioscopy (and goniophotography) was performed. Thereafter, 50 cats were treated unilaterally with one drop of 0.5% tropicamide. The contralateral, left eye served as a control. In the placebo group consisting of 20 cats, one drop of physiologic saline solution was administered to the right eye. In all cats, IOP of both eyes was measured 30, 60 and 90 min after topical administration. After unilateral tropicamide application, IOP increased significantly both in the right and in the left eye. Maximum average IOP increase was observed at the control measurement performed 90 min after treatment, with an elevation of 3.8 +/- 4.2 mmHg in the right eye and 3.5 +/- 3.6 mmHg in the left eye. Maximum IOP increase after treatment was 18.0 mmHg in the treated eye and 17.0 mmHg in the left eye. Measurements made at 60 min after treatment revealed a significantly higher increase in IOP in the right eye as compared to the left eye (P60 < 0.05), whereas the differences between right and left eye in IOP increase were not significant at 30 and 90 min after mydriatic application (P30 = 0.123; P90 = 0.305). Although tropicamide-induced mydriasis was observed in the treated eye, the contralateral eye did not show any changes in pupillary function at any time. With increasing age of the cats, IOP increase was found to be more moderate, whereas the gender of the cats did not have any significant influence on IOP changes. In the 20 cats in the placebo group, no significant changes in IOP were observed. We conclude that topical 0.5% tropicamide causes a significant elevation of IOP in the treated and untreated eye in normal cats.


Sexual Satisfaction Among Infertile Couples: Demographics and Psychosocial Health Factors.
The purpose of the current study was to explore sexual satisfaction among infertile couples in Jordan and its associations with psychosocial and sociodemographic factors. Using a descriptive correlational design, 248 infertile couples from outpatient clinics were recruited and filled out a questionnaire on sexual satisfaction, in addition to perceived social support, depressive symptoms, psychological stress, coping skills, optimism, life satisfaction, and sociodemographics. Sexual satisfaction was significantly and positively correlated with perceived social support, optimism, life satisfaction, and coping. Stronger association was observed between sexual satisfaction and optimism. No difference was found in sexual satisfaction in relation to participants' gender, age, working status, or education. This study highlights the importance of building mental health nurses' competence to provide education and counseling on sexuality to improve the quality of life of infertile couples and optimize their sexual wellness. The most recent guidelines for psychosocial care for infertile couples are discussed. [Journal of Psychosocial Nursing and Mental Health Services, 58(9), 40-47.].


The gene causing the Best's macular dystrophy (BMD) encodes a putative ion exchanger.
Best's macular dystrophy (BMD), also known as vitelliform macular degeneration type 2, is an autosomal dominant disease that causes loss of vision. The causative gene encodes a 585 amino acids protein called bestrophin with unknown function. From bioinformatics analysis, a putative ion exchanger function for bestrophin can be suggested.


Multiple Ca2+ channel types coexist to regulate synaptosomal neurotransmitter release.
The regulation of excitation-secretion coupling by Ca2+ channels is a fundamental property of the nerve terminal. Peptide toxins that block specific Ca2+ channel types have been used to identify which channels participate in neurotransmitter release. Subsecond measurements of [3H]-glutamate and [3H]dopamine release from rat striatal synaptosomes showed that P-type channels, which are sensitive to the Agelenopsis aperta venom peptide omega-Aga-IVA, trigger the release of both transmitters. Dopamine (but not glutamate) release was also controlled by N-type, omega-conotoxin-sensitive channels. With strong depolarizations, where neither toxin was very effective alone, a combination of omega-Aga-IVA and omega-conotoxin produced a synergistic inhibition of 60-80% of Ca(2+)-dependent dopamine release. The results suggest that multiple Ca2+ channel types coexist to regulate neurosecretion under normal physiological conditions in the majority of nerve terminals. P- and N-type channels coexist in dopaminergic terminals, while P-type and a omega-conotoxin- and omega-Aga-IVA-resistant channel coexist in glutamatergic terminals. Such an arrangement could lend a high degree of flexibility in the regulation of transmitter release under diverse conditions of stimulation and modulation.


Cardiogenic pulmonary oedema: alarmingly poor long term prognosis. Analysis of risk factors.
Acute heart failure (AHF) is a life-threatening condition associated with poor prognosis. To investigate the long term prognosis and identify prognostic factors among patients who were discharged after an episode of cardiogenic pulmonary oedema. We enrolled 84 patients (M: 56%, n = 47) who were discharged with cardiogenic pulmonary oedema as a diagnosis. Clinical, biochemical and echocardiographic variables were collected and analysed. The completeness of two- and five-year follow-up was 100% and 96%, respectively. The median (IQR) age was 74 years (64-81), left ventricular ejection fraction was 35% (27-45), blood pressure on admission was 140/90 mm Hg (115-180/70-100), estimated glomerular filtration rate was 60 mL/min/1.73 m2 (45-73). Forty per cent (n = 34) of the patients had a history of atrial fibrillation (AF), however, AF was directly involved with pulmonary oedema only in 4% (n = 3) of the cases. Acute myocardial infarction (AMI) accounted for 34% (n = 29) of all the causes of pulmonary oedema and was associated with a better two-year prognosis compared to other causes of pulmonary oedema (p = 0.018). Two- and five-year mortality was 45% (n = 38) and 72% (n = 58), respectively. Co-morbidities were common. Ischaemic heart disease and arterial hypertension were present in 83% and 70% of the patients, respectively. Multivariable analysis identified increased left ventricular mass (RR 3.609, 95% CI 1.235-10.547, p = 0.017) and treatment with long-acting vasodilator drugs (LAVDs) (RR 4.881, 95% CI 1.618-14.727, p = 0.004) as independent negative prognostic factors, whereas in-hospital therapy with beta-blockers created a distinctly protective effect (RR 0.123, 95% CI 0.033-0.457, p = 0.002) in the two-year follow-up. Five-year mortality was independently associated with older age (RR 1.08, 95% CI 1.02-1.14, p = 0.005) and treatment with LAVDs (RR 6.4, 95% CI 1.47-28.14, p = 0.012), while percutaneous coronary intervention (RR 0.17, 95% CI 0.05-0.58, p = 0.004) significantly decreased the risk. AHF is a heterogeneous syndrome with a very high remote mortality. LAVDs administered during the hospital stay as well as older age on admission correlate with higher long-term overall mortality. In the age of percutaneous coronary intervention, AMI aetiology of pulmonary oedema is no longer a negative prognostic factor for the long-term prognosis.


Adaptive analysis of optical fringe patterns using ensemble empirical mode decomposition algorithm.
An approach based on a novel technique, called ensemble empirical mode decomposition, is proposed to adaptively reduce noise and remove background intensity from a two-dimensional fringe pattern. It can solve the mode-mixing problem of the original empirical mode decomposition caused by the existence of intermittent noise in fringe signals. Then a strategy is developed to automatically identify and group the resulting intrinsic mode functions for the purpose of eliminating noise and background of the fringe pattern. This approach is applied to process the simulated and practical fringe patterns, compared with Fourier transform and wavelet methods.


Novel mutations and SNPs identified in CCR2 using a new comprehensive denaturing gradient gel electrophoresis assay.
A single nucleotide polymorphism (SNP) at codon 64 in the CC chemokine receptor 2 gene (CCR2 V64I) has been associated with a dominant effect of delaying disease progression from human immunodeficiency virus-1 (HIV-1) infection to acquired immunodeficiency syndrome (AIDS). The objective of our study was to design a comprehensive mutation detection assay for the entire coding region of the CCR2A and CCR2B gene transcripts, including all relevant splice site junctions and to identify novel mutations and SNPs within our predominantly African-based population, which could influence an individual's susceptibility to HIV-1 infection and/or progression to AIDS. The mutation detection assay, based on denaturing gradient gel electrophoresis (DGGE), allowed for the complete analysis of five individuals per denaturing gel. Our study cohort consisted of 102 HIV seropositive patients and 144 HIV seronegative controls from the diverse South African population. Application of the CCR2-DGGE assay resulted in the detection of two previously reported CCR2 polymorphisms, namely CCR2 V64I and CCR2 N260N, and 11 novel mutations, including seven SNPs occurring at high allelic frequencies within specific population groups of South Africa. The large number of novel mutations/SNPs identified, using the CCR2-DGGE assay, indicates the importance for comprehensive analysis of all candidate genes in host susceptibility to HIV-1 infection, specifically in the under-studied African-based populations.


In one harness: the interplay of cellular responses and subsequent cell fate after quantum dot uptake.
Rapid growth and expansion of engineered nanomaterials will occur when the technology can be used safely. Quantum dots have excellent prospects in clinical applications, but the issue of toxicity has not yet been resolved. To enable their medical implementation, the effect on, and mechanisms in, live cells should be clearly known and predicted. A massive amount of experimental data dedicated to nanotoxicity has been accumulated to-date, but it lacks a logical structure. The current challenge is to organize existing knowledge into lucid biological and mathematical models. In our review we aim to describe the interplay of various cell death mechanisms triggered by quantum dots as a consequence of particle parameters and experimental conditions.


Enhancement of Heat Dissipation by Laser Micro Structuring for LED Module.
Optimization for heat dissipation plays a significant role in energy saving and high-efficiency utilizing of integrated electronics. In this paper, we present a study of micro structuring on polymer-based flexible substrate coupled with aluminum-alloy heat sink. The heat dissipation performance was investigated by temperature evolution of a heat sink under natural convection by infrared (IR) camera, and results showed that the heat dissipation enhancement could be up to 25%. Moreover, the heat dissipation performance of a typical heat sink in terms of light-emitting diode (LED) hip was investigated via both thermal transient measurement and the finite element analysis (FEA). The maximum LED chip temperature of the laser-textured heat sink was approximately 22.4% lower than that of the as-received heat sink. We propose that these properties accompanied with the simplicity of fabrication make laser surface texturing a promising candidate for on-chip thermal management applications in electronics.


Comparison of the various techniques of identifying human spermatozoa morphology.
The morphology of 100 subjects' spermatozoa was examined with 6 different methods of identification. Mean results obtained were compared with each other, analyzing variances for two criteria of classification. Analysis of statistics shows that these 6 methods make a heterogeneous group. In particular, observations carried out with phase contrast and with Testsimplets self-colouring slides showed a significantly higher number of anomalies than with other methods. Papanicolau, hematoxylin-eosin and modified Giemsa staining gave an intermediate number of anomalies, which were statistically indistinguishable from each other. Hemaquick rapid staining agents for hematology gave the lowest percentage of anomalies. Differentiated analysis of anomalous heads, necks and tails showed that the 6 methods may differ in their capacity to identify the various anomalies. Given that the percentage of observed normal forms is inversely proportional to the effectiveness of a specific method in identifying anomalies, then it is evident that the choice of method is the decisive factor when defining criteria of normality.


Nanoimprint lithography for nanophotonics in silicon.
A novel inverse imprinting procedure for nanolithography is presented which offers a transfer accuracy and feature definition that is comparable to state-of-the-art nanofabrication techniques. We illustrate the fabrication quality of a demanding nanophotonic structure: a photonic crystal waveguide. Local examination using photon scanning tunneling microscopy (PSTM) shows that the resulting nanophotonic structures have excellent guiding properties at wavelengths in the telecommunications range, which indicates a high quality of the local structure and the overall periodicity.


Cloning, identification, and expression analysis at the stage of gonadal sex differentiation of chicken miR-363 and 363*.
miRNAs (microRNAs) are small, functional, non-coding RNAs and have been proved to implicate in regulation of diverse biological processes ranging from cell differentiation to organism development. With the purpose of exploring the roles of miRNAs on chicken embryo sexual determination and gonadal differentiation, we cloned and identified the stem-loop precursor structure (GenBank accession no. GU597370) of chicken miR-363 and 363* followed by studying their temporal and spatial expression patterns in chicken embryo at the stage of E3.5-6.5 d (embryonic days 3.5-6.5) by semi-quantitative RT-PCR and WISH (whole-mount in situ hybridization) in this study. The results showed that miR-363* located in cloned sequence of unknown segment in chicken genome, and flanking sequence of miR-363 and 363* according to the structural features of miRNAs precursor. Significantly differential expression (P < 0.05) of gga-miR-363 between female and male chicken embryonic gonads was found at E4.5 and 6.5 d, but the differential expression of gga-miR-363* from E3.5 to 6.5 d between both sexes fell short of significant level. The results of WISH indicated that expression signals of gga-miR-363 mainly appeared at limb bud, notochord, ectoderm, brain in E4.5 d chicken embryo, and urogenital systems (UGSs) at E6.5 d, and the expression level of E6.5 d was higher in the female than that in the male. It can be speculated that gga-miR-363 would involve in the gonadal development and gga-miR-363* might have transient regulatory functions during the early stages of chicken embryo development.


Quantum coherence spectroscopy reveals complex dynamics in bacterial light-harvesting complex 2 (LH2).
Light-harvesting antenna complexes transfer energy from sunlight to photosynthetic reaction centers where charge separation drives cellular metabolism. The process through which pigments transfer excitation energy involves a complex choreography of coherent and incoherent processes mediated by the surrounding protein and solvent environment. The recent discovery of coherent dynamics in photosynthetic light-harvesting antennae has motivated many theoretical models exploring effects of interference in energy transfer phenomena. In this work, we provide experimental evidence of long-lived quantum coherence between the spectrally separated B800 and B850 rings of the light-harvesting complex 2 (LH2) of purple bacteria. Spectrally resolved maps of the detuning, dephasing, and the amplitude of electronic coupling between excitons reveal that different relaxation pathways act in concert for optimal transfer efficiency. Furthermore, maps of the phase of the signal suggest that quantum mechanical interference between different energy transfer pathways may be important even at ambient temperature. Such interference at a product state has already been shown to enhance the quantum efficiency of transfer in theoretical models of closed loop systems such as LH2.


Induction therapy for patients with multiple sclerosis: why? When? How?
The concept of induction treatment followed by long-term maintenance treatment in multiple sclerosis (MS) has attracted considerable attention. The combination of mitoxantrone as the induction therapy followed by an immunomodulatory drug (e.g., interferon beta or glatiramer acetate) as the maintenance therapy is of particular interest. This approach is suitable for patients with particularly aggressive disease, characterised by frequent relapses with incomplete recovery and the accumulation of focal lesions visible on magnetic resonance imaging. A long-term study has shown that a short (6 month) course of mitoxantrone followed by maintenance therapy with an immunomodulatory drug brings about a rapid reduction in disease activity and subsequent sustained disease control for at least 5 years. Furthermore, randomised studies have demonstrated that induction with mitoxantrone followed by maintenance treatment affords better disease control than monotherapy with an interferon beta. Natalizumab is also effective in patients with very active MS, but has a propensity to result in rebound inflammatory disease activity on withdrawal. More recently, a mere 5-day course of 12-mg intravenous perfusions of alemtuzumab was found to bring long-term clinical benefits in early relapsing MS patients at risk of developing severe systemic autoimmune disease within the space of a few years.


[Diagnostic significance and clinical application of specific chimeric genes in soft tissue sarcomas by RT-PCR using paraffin-embedded tissues: a study of 103 specimens].
To investigate the expression of the chimeric genes resulting from the specific chromosomal translocations in soft tissue sarcomas (STS) and its diagnostic significance for STS. The variety of fusion transcripts were detected in 103 cases of STS, including 30 cases of synovial sarcoma (SS), 15 cases of rhabdomyosarcoma (RMS), 25 cases of Ewing's sarcoma/peripheral primitive neuroectodermal tumors (ES/pPNET), 12 cases of dermatofibrosarcoma protuberans (DFSP), 14 cases of aveolar soft part sarcoma (ASPS), 3 cases of leiomyosarcoma (LMS), 2 cases of malignant fibrous histocytoma (MFH), and 2 cases of fibrosarcoma (FS); and 20 cases of control tumors by reverse transcription-polymerase chain reaction (RT-PCR) using formalin fixed, paraffin embedded specimens. Of the 34 cases of SS 28 (93.3%) expressed SSX-SYT chimeric transcripts (14 were positive for SYT-SSX1, 9 for SYT-SSX2). Four of the six cases of alveolar RMS had a PAX3/PAX7-FKHR fusion transcript. None of the 9 cases of embryonic and polymorphic RMS expressed PAX3/PAX7-FKHR. Of the 25 cases of ES/pPNET, 19 were positive for EWS-FLI1 fusion transcript and 1 for EWS-ERG fusion transcript. COL1A1-PDGFB fusion transcript was expressed in 8 of the 12 cases (66.7%) of DFSP. Of the fourteen cases of ASPS, ten expressed ASPL-TFE3 fusion transcript. None of the 3 cases of LMS, 2 cases of MFH, 2 cases of FS, and 20 control cases contained any of the fusion transcript. Chimeric gene transcript resulting from specific chromosomal translocations is a reliable index for the molecular diagnosis of STS and RT-PCR assay for detection of specific fusion gene provides a useful tool for confirmation of the diagnosis of STS in diagnostically difficult cases and in retrospective studies.


Profile of bavituximab and its potential in the treatment of non-small-cell lung cancer.
Bavituximab is a an unconjugated, chimeric immunoglobulin G1 (IgG1) monoclonal antibody directed against the phosphatidylserine (PS) expressed on tumor endothelium, with a specific mechanism of action. PS is an anionic membrane phospholipid, physiologically restricted to the internal membrane leaflet; various pathophysiologic processes cause the exposure of PS on the external membrane leaflet. Bavituximab, once bound, starts up host effector activities, such as antibody dependent cellular cytotoxicity, causing vessel destruction and enhancing antitumor immunity. Phase I clinical trials of bavituximab administered as monotherapy or in combination with other chemotherapeutic agents in adults with pretreated solid tumors have been accomplished, indicating that bavituximab can be safely dispensed weekly, with a recommended dose of 1 and 3 mg/kg. A Phase II randomized, placebo-controlled trial of bavituximab plus docetaxel, in the second-line therapy setting of locally advanced or metastatic non-small-cell lung cancer, has been conducted and recently presented, suggesting a clinical benefit of the combination, with an overall response rate of 17% and median overall survival of more than 11 months. A Phase III trial is currently ongoing. Bavituximab has been studied in combination with platinum-based doublets with promising results. In the present paper we summarize the preclinical development and clinical experience with bavituximab in non-small-cell lung cancer.


Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets.
Aging is the major risk factor for neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. A large body of evidence indicates that oxidative stress is involved in the pathophysiology of these diseases. Oxidative stress can induce neuronal damages, modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. Thus antioxidants have been studied for their effectiveness in reducing these deleterious effects and neuronal death in many in vitro and in vivo studies. Increasing number of studies demonstrated the efficacy of polyphenolic antioxidants from fruits and vegetables to reduce or to block neuronal death occurring in the pathophysiology of these disorders. These studies revealed that other mechanisms than the antioxidant activities could be involved in the neuroprotective effect of these phenolic compounds. We will review some of these mechanisms and particular emphasis will be given to polyphenolic compounds from green tea, the Ginkgo biloba extract EGb 761, blueberries extracts, wine components and curcumin.


Paludibacterium purpuratum sp. nov., isolated from wetland soil.
A novel bacterium, designated KJ031T, was isolated from a wetland soil sample taken from Jeju island, Republic of Korea. Cells were Gram-stain-negative, curved rod shaped, oxidase- and catalase- positive, motile and facultatively anaerobic. Growth was observed at pH 6.0-8.0 and at 20-37 °C on R2A agar. Comparative analysis of 16S rRNA gene sequences revealed that strain KJ031T is a member of the genus Paludibacterium, sharing highest sequence similarities with Paludibacterium paludis KBP-21T (96.2 %) and Paludibacterium. yongneupense 5YN8-15T (96.0 %). The major fatty acids were summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), C16 : 0 and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The predominant respiratory quinone was Q-8. The major polar lipids of strain KJ031T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, one unidentified aminophospholipid, two unidentified phospholipids and one unidentified polar lipid. The DNA G+C content was 59.2 mol%. On the basis of the evidence presented in this study, strain KJ031T represents a novel species of the genus Paludibacterium, for which the name Paludibacterium purpuratum sp. nov. is proposed. The type strain is KJ031T (=KCTC 42852T =CECT 8976T).


Plasma fibrinogen and coronary heart disease in elderly Japanese-American men.
Clinical and epidemiological studies consistently indicate that elevations in plasma fibrinogen concentration are associated with the presence and development of coronary heart disease (CHD). These elevations are strongly correlated with smoking behavior and may play a significant role in mediating a relation of smoking to CHD. This cross-sectional survey of 3571 elderly Japanese-American men, aged 71 through 93 years, represents survivors of the Honolulu Heart Program cohort. Active smokers are almost twice as likely to be represented in the highest quintile of the fibrinogen distribution compared with the lowest quintile (9.8% versus 5.3%, respectively). The highest prevalence of CHD (34%) was noted in past and current smokers who were in the highest quintile of fibrinogen. The age-adjusted relative odds of prevalent CHD comparing the average fibrinogen levels in the first and fifth quintiles were 1.36 (95% confidence interval, 1.13 to 1.64). After adjustment for smoking status, blood pressure, total and HDL cholesterol, diabetes status, hematocrit, and white cell count, the association between fibrinogen and CHD was changed slightly and remained statistically significant (P < .05). These findings in an elderly cohort of Japanese-American men are consistent with previous studies among middle-aged adults demonstrating fibrinogen to be associated with indicators of clinical CHD and CHD risk factors. Because of the cross-sectional nature of this study, it is not possible to distinguish whether the observed relation of fibrinogen to prevalent CHD is causal or whether it represents a marker of active and progressive disease.