Histochemical reactivity and staining properties of functionally defined cell types in the human adenohypophysis.
Histochemical properties and histologic staining characteristics of a variety of procedures are delineated for the three types of adenohypophyseal mucoid cells whose function has been identified by immunostaining methods. Content of glycoprotein hormones may, in part, account for the periodic acid-Schiff (PAS) reactivity in the thyrotropic and gonadotropic but not the melanocorticotropic cell types. The melanocorticotropic cells evidence basophilia attributable to sialic acid residues, sulfate esters and possibly an additional unidentified component with atypical reactivity. The finding that basophilia of thyrotropic and gonadotropic cells appears largely attributable to sulfate esters indicates the presence of acid mucosubstance other than the glycoprotein hormone in these cells. The effect of oxidation in inducing basophilia indicative of cysteine- or cystine-rich protein varies in the different cell types. Melanocorticotropic cells alone among the mucoid group evidenced content of strongly basic protein, demonstrating stronger affinity for the acid dye Biebrich scarlet than the classic acidophils.


Transepithelial transport of the bioactive tripeptide, Val-Pro-Pro, in human intestinal Caco-2 cell monolayers.
Some of the food-derived tripeptides with angiotensin converting enzyme (ACE)-inhibitory activity have been reported to be hypotensive after being orally administered. The mechanism for the intestinal transport of these tripeptides was studied by using monolayer-cultured human intestinal Caco-2 cells which express many enterocyte-like functions including the peptide transporter (PepT1)-mediated transport system. Val-Pro-Pro, an ACE-inhibitory peptide from fermented milk, was used as a model tripeptide. A significant amount of intact Val-Pro-Pro was transported across the Caco-2 cell monolayer. This transport was hardly inhibited by a competitive substrate for PepT1. Since no intact Val-Pro-Pro was detected in the cells, Val-Pro-Pro apically taken by Caco-2 cells via PepT1 was likely to have been quickly hydrolyzed by intracellular peptidases, producing free Val and Pro. These findings suggest that PepT1-mediated transport was not involved in the transepithelial transport of intact Val-Pro-Pro. Paracellular diffusion is suggested to have been the main mechanism for the transport of intact Val-Pro-Pro across the Caco-2 cell monolayer.


Continuous Meter-Scale Wet-Spinning of Cornlike Composite Fibers for Eco-Friendly Multifunctional Electronics.
"Green" solvent-dissolved cellulose enables functional reuse of waste cotton fabrics. This work will not only achieve high-value utilization of biomass but also overcome microplastic pollution. There is a significant challenge in the continuous meter-scale synthesis of sensing fibers for commercial applications with high productivity. Herein, waste cellulose fabrics was recycled by the NaOH/urea system to produce regenerated cellulose (RC) and then cornlike polyaniline (PANI) was anchored on the RC fibers by in situ polymerization of aniline through continuous meter-scale wet-spinning. In our findings, the morphologies and possible growth of PANI layers on the RC surface can be tailored by various ammonium persulfate (APS) contents in a coagulation bath. Especially, composite fibers (PC0.5) exhibited superior electrical conductivity and highly sensitive responsiveness to organic vapors and human motions including exhalation/inhalation, finger, and wrist joints. Further, the possible sensing mechanism of cornlike PC0.5 has been proposed, and its GF value is 23.8. This study realized the conversion from cheap waste fibers to high-value conductive fibers with excellent performances for multifunctional wearable sensors and energy devices via a simple and "green" method.


Multishelled Hollow Structures of Yttrium Oxide for the Highly Selective and Ultrasensitive Detection of Methanol.
Methanol is extremely harmful to human health, since it is oxidized slowly and can accumulate in the human body. Therefore, it is essential to develop a methanol gas sensing technology with high sensitivity and selectivity for use in environmental monitoring and healthcare. In this work, a simple and low-cost sensor based on a Y2 O3 multishelled hollow structure (YMSH) to selectively detect methanol with an ultrasensitive limit of detection (71 ppb) is developed. The unique multishelled hollow structure with a large surface area and exposed {222} facets makes an important contribution to the ultrasensitive detection of methanol, which is further confirmed by subsequent theoretical simulations. Moreover, in situ Fourier transform infrared spectra verify that CO2 is the final product, which indicates a high catalytic activity of the YMSHs toward methanol oxidation. Interestingly, the sensor can also be applied to liquor samples that are mixtures of ethanol, methanol, and water, which provides a facile way to detect methanol in wines. This sensor represents a unique and highly sensitive means to detect methanol, which has great promise for potential application in environmental monitoring and food safety inspection.


The twisted structure of the rat Achilles tendon.
The rat is frequently used as a model to study the characteristics, aetiology and pathology of the Achilles tendon. However, though the structure of the human Achilles tendon has been extensively investigated, the anatomical structure of the rat Achilles tendon remains unclear, which impedes the ability to use rats to study Achilles tendinopathy. The purpose of this study was to reveal the structure of the rat Achilles tendon and to explore its similarities with the human Achilles tendon through an anatomical dissection of 80 rat Achilles tendons (40 female, 40 male). This study found that the subtendons of the rat Achilles tendon originating from the triceps surae muscle were twisted, and each subtendon also had its own torsion. The extent of these two types of torsion could be very different between rats. Alterations in this torsion may result in distinct stress fields in the Achilles tendon, which may play a critical role in the pathogenesis of Achilles tendinopathy. This study provides an important basis to support the use of rats as model animals to investigate the characteristics of the human Achilles tendon and Achilles tendinopathy.


Effectiveness of statins in Medicare-eligible patients and patients < 65 years using clinical practice data.
This study compared effectiveness of rosuvastatin (RSV) with other statins on lowering LDL-C and LDL-C goal attainment among Medicare-eligible patients (age >or= 65 years) and patients with age < 65 years treated in usual clinical practice to provide evidence of real-world effectiveness of statins. Retrospective cohort study was conducted in patients, newly prescribed statin therapy during August 2003 to May 2005. Patient inclusion criteria: no prior prescription for dyslipidaemic medication in the preceding 12 months, continuously enrolled for >or= 15 months and >or= 90-day supply of statin. Effectiveness of RSV in reducing LDL-C and attaining LDL-C goal when compared with other statins was evaluated using multivariate regression, adjusting for baseline LDL-C, age, gender, smoking, hypertension, coronary heart disease (CHD), systolic blood pressure and therapy duration. Adjusted per cent LDL-C reduction was significantly greater (p < 0.05) with RSV (24.3% for >or= 65 and 28.5% for < 65) compared with ATV (17.5%, 21.3%), SMV (14.8%, 18.4%), PRV (11.3%, 15.8%), FLV (10.7%, 20.6%) and LOV (13.3%, 14.4%). Among patients in both age groups at high or moderate CHD risk, a greater proportion of RSV patients attained LDL-C goal (76.0% for age group >or= 65 years and 78.4% for age group < 65 years) vs. 50.5-73.0% for >or= 65 and 51.3-71.5% for < 65 years of age on other statins (p < 0.0001). Rosuvastatin is more effective in lowering LDL-C in Medicare-eligible patients and patients < 65 years of age when compared with other statins in usual clinical practice. Moreover, RSV patients had higher LDL-C goal attainment rates when compared with other statins in high- and moderate-risk patients. The study results have implications for clinicians in selecting the optimal statin to meet individual patient care needs.


[A comparative evaluation of the effect of an extremely high-frequency electromagnetic field on cerebral hemodynamics in hypertension patients exposed in different reflexogenic areas].
A single session and multiple sinocarotid and temporal exposures to EHF electromagnetic field in patients with stage I and II hypertension had different effects on cerebral circulation Variants of the above treatment are proposed.


A transdermal drug delivery system based on dissolving microneedles for boron neutron capture therapy of melanoma.
Boron neutron capture therapy (BNCT) is a promising therapy for malignant tumors that requires selective and high concentrations of 10B accumulation in tumor cells. Despite ongoing developments in novel boron agents and delivery carriers, the progress and clinical application of BNCT is still restricted by the low 10B accumulation and tumor-to-normal tissue (T/N) ratio. Herein, a dissolving microneedle-based transdermal drug delivery system was specifically designed for BNCT in a mouse model of melanoma. By incorporating fructose-BPA (F-BPA) into PVA microneedle tips, this system successfully delivered sufficient F-BPA into the melanoma site after the application of only two patches. Notably, the T/N ratio achieved through the treatment combining PVA/F-BPA MNs with BNCT (PVA/F-BPA MNs-BNCT) surpassed 93.16, signifying a great improvement. Furthermore, this treatment approach effectively inhibited tumor growth and significantly enhanced the survival rate of the mice. In brief, our study introduces a novel, simple, and efficient administration strategy for BNCT, opening new possibilities for the design of nanomedicine for BNCT.


Condensin function at centromere chromatin facilitates proper kinetochore tension and ensures correct mitotic segregation of sister chromatids.
The condensin complex is essential for sister chromatid segregation in eukaryotic mitosis. Nevertheless, in budding yeast, condensin mutations result in massive mis-segregation of chromosomes containing the nucleolar organizer, while other chromosomes, which also contain condensin binding sites, remain genetically stable. To investigate this phenomenon we analyzed the mechanism of the cell-cycle arrest elicited by condensin mutations. Under restrictive conditions, the majority of condensin-deficient cells arrest in metaphase. This metaphase arrest is mediated by the spindle checkpoint, particularly by the spindle-kinetochore tension-controlling pathway. Inactivation of the spindle checkpoint in condensin mutants resulted in frequent chromosome non-disjunction, eliminating the bias in chromosome mis-segregation towards rDNA-containing chromosomes. The spindle tension defect in condensin-impaired cells is likely mediated by structural defects in centromere chromatin reflected by the partial loss of the centromere histone Cse4p. These findings show that, in addition to its essential role in rDNA segregation, condensin mediates segregation of the whole genome by maintaining the centromere structure in Saccharomyces cerevisiae.


Reducing the dimensionality of the protein-folding search problem.
How does a folding protein negotiate a vast, featureless conformational landscape and adopt its native structure in biological real time? Motivated by this search problem, we developed a novel algorithm to compare protein structures. Procedures to identify structural analogs are typically conducted in three-dimensional space: the tertiary structure of a target protein is matched against each candidate in a database of structures, and goodness of fit is evaluated by a distance-based measure, such as the root-mean-square distance between target and candidate. This is an expensive approach because three-dimensional space is complex. Here, we transform the problem into a simpler one-dimensional procedure. Specifically, we identify and label the 11 most populated residue basins in a database of high-resolution protein structures. Using this 11-letter alphabet, any protein's three-dimensional structure can be transformed into a one-dimensional string by mapping each residue onto its corresponding basin. Similarity between the resultant basin strings can then be evaluated by conventional sequence-based comparison. The disorder → order folding transition is abridged on both sides. At the onset, folding conditions necessitate formation of hydrogen-bonded scaffold elements on which proteins are assembled, severely restricting the magnitude of accessible conformational space. Near the end, chain topology is established prior to emergence of the close-packed native state. At this latter stage of folding, the chain remains molten, and residues populate natural basins that are approximated by the 11 basins derived here. In essence, our algorithm reduces the protein-folding search problem to mapping the amino acid sequence onto a restricted basin string.


The correlation theory of the chemical bond.
The quantum mechanical description of the chemical bond is generally given in terms of delocalized bonding orbitals, or, alternatively, in terms of correlations of occupations of localised orbitals. However, in the latter case, multiorbital correlations were treated only in terms of two-orbital correlations, although the structure of multiorbital correlations is far richer; and, in the case of bonds established by more than two electrons, multiorbital correlations represent a more natural point of view. Here, for the first time, we introduce the true multiorbital correlation theory, consisting of a framework for handling the structure of multiorbital correlations, a toolbox of true multiorbital correlation measures, and the formulation of the multiorbital correlation clustering, together with an algorithm for obtaining that. These make it possible to characterise quantitatively, how well a bonding picture describes the chemical system. As proof of concept, we apply the theory for the investigation of the bond structures of several molecules. We show that the non-existence of well-defined multiorbital correlation clustering provides a reason for debated bonding picture.


Integrated motivational interviewing and cognitive behaviour therapy can increase physical activity and improve health of adult ambulatory care patients in a regional hospital: the Healthy4U randomised controlled trial.
The aim of this study was to determine whether a twelve-week, health coaching intervention could result in changes in physical activity, anthropometrics and health-related outcomes in adults presenting to an ambulatory hospital clinic. Seventy-two participants who reported being insufficiently active were recruited from an ambulatory hospital clinic and randomised to an intervention group that received an education session and eight 30-min telephone sessions of integrated motivational interviewing and cognitive behaviour therapy (MI-CBT), or to a control group that received the education session only. ActiGraph GT3X accelerometers were used to measure moderate-to-vigorous physical activity at baseline, post-intervention (3-months) and follow-up (6-months). Secondary outcome measures (anthropometrics, physical activity self-efficacy, health-related quality of life, type 2 diabetes risk) were also assessed at the three time points. At baseline, the mean age and body mass index of participants (n = 72, 75% females) were 53 ± 8 years and 30.8 ± 4.1 kg/m2, respectively. Treatment group influenced the pattern of physical activity over time (p < 0.001). The intervention group increased moderate-to-vigorous physical activity from baseline to post-intervention and remained elevated at follow-up by 12.9 min/day (95%CI: 6.5 to 19.5 min/day). In contrast, at follow-up the control group decreased moderate-to-vigorous physical activity by 9.9 min/day (95%CI: -3.7 to -16.0 min/day). Relative to control, at follow-up the intervention group exhibited beneficial changes in body mass (p < 0.001), waist circumference (p < 0.001), body mass index (p < 0.001), physical activity self-efficacy (p < 0.001), type 2 diabetes risk (p < 0.001), and health-related quality of life (p < 0.001). This study demonstrates that a low contact coaching intervention results in beneficial changes in physical activity, anthropometrics and health-related outcomes that were maintained at follow-up in adults who report being insufficiently active to an ambulatory care clinic. ANZCTR: ACTRN12616001331426 . Registered 23 September 2016.


Urinary incontinence, overactive bladder, and other lower urinary tract symptoms: a longitudinal population-based survey in men aged 45-103 years.
Lower urinary tract symptoms (LUTS) such as urinary incontinence (UI) and overactive bladder (OAB) are highly prevalent conditions, but there are few studies describing progression and remission of LUTS in men, especially over the long term. To describe the prevalence of UI, OAB, and LUTS using current International Continence Society definitions in the same men studied longitudinally over time. Prospective, population-based, longitudinal study. In 1992, 10 458 men aged 45-99 yr, resident in the city of Gothenburg, were selected at random from the Population Register. The men received a postal questionnaire about the presence of LUTS, as well as questions on social, medical, health-related quality of life (HRQoL), and demographic data. Responders in 1992 were reassessed 11 yr later in 2003 using a similar questionnaire. In 2003, 4072 of the 7763 men who responded in 1992 were still available in the Population Register and 3257 men (80%) aged 56-103 yr, responded. Prevalence of UI and OAB had increased (p<0.01) in the same men assessed in 1992 (4.5% and 15.6%, respectively) and 2003 (10.5% and 44.4%, respectively). The prevalence of nocturia, urgency, slow stream, hesitancy, incomplete emptying, postmicturition dribble, and the number of daytime micturitions had also increased (p<0.01). Only a minority reported regression of symptoms. Men with UI or OAB reported a poorer (p<0.001) HRQoL compared with men without UI or OAB. There was a marked increase in the prevalence of UI, OAB, and other LUTS in the same men assessed longitudinally over this 11-yr period. UI and OAB had a negative influence on HRQoL, and men who developed UI or OAB had a greater deterioration in HRQoL than men who had no change in their UI/OAB status over time.


Analysis of immersed silica optical microfiber knot resonator and its application as a moisture sensor.
An embedded silica optical microfiber knot resonator humidity sensor is presented. As silica has a poor response to environmental humidity changes, a surrounding layer of Nafion is used as a transducer. Spectral characterization and also a procedure to determine the coupling and total loss coefficients are presented. Sensitivity as high as (0.29±0.01) nm/% relative humidity has been noticed. Possible issues that emerge from the use of Nafion such as bulk swelling, refractive index hysteresis, as well as a saturation process, are discussed.


ncRDeathDB: A comprehensive bioinformatics resource for deciphering network organization of the ncRNA-mediated cell death system.
Programmed cell death (PCD) is a critical biological process involved in many important processes, and defects in PCD have been linked with numerous human diseases. In recent years, the protein architecture in different PCD subroutines has been explored, but our understanding of the global network organization of the noncoding RNA (ncRNA)-mediated cell death system is limited and ambiguous. Hence, we developed the comprehensive bioinformatics resource (ncRDeathDB, www.rna-society.org/ncrdeathdb ) to archive ncRNA-associated cell death interactions. The current version of ncRDeathDB documents a total of more than 4600 ncRNA-mediated PCD entries in 12 species. ncRDeathDB provides a user-friendly interface to query, browse and manipulate these ncRNA-associated cell death interactions. Furthermore, this resource will help to visualize and navigate current knowledge of the noncoding RNA component of cell death and autophagy, to uncover the generic organizing principles of ncRNA-associated cell death systems, and to generate valuable biological hypotheses.


[Sex hormones, immune disorders, and inflammatory rheumatic diseases].
It is a well-documented fact that sex hormones are implicated in the immune response and that androgens and estrogens modulate susceptibility and progression of autoimmune rheumatic diseases. Estrogens are considered to stimulate cell proliferation and humoral immune responses while androgens exert suppressive effects on both humoral and cellular immune responses. Autoimmune diseases are common in females, especially during the generative period, the most representative of estrogen-related autoimmune diseases being systemic lupus erythematosus. Estrogens and androgens are involved in the pathogenesis of the disease; both exogenous and endogenous estrogens are strong stimulators of cytokine production and disease activity. Some physiological conditions, as well as some drugs and chronic stress, can modulate hormone levels. Low levels of gonadal androgens have been detected in body fluids of both male and female rheumatoid arthritis patients, supporting the possibility of the pathogenic role for decreased androgen levels. Views on hormone replacement therapy or hormonal contraception in rheumatic diseases have been modified and in most rheumatic diseases, including rheumatoid arthritis, hormones are not prohibited. There are still controversies regarding systemic lupus; the new standpoint being that hormonal contraception is not contraindicated in women with inactive or stable active SLE, except for those with positive antiphospholipid antibodies.


Response of mouse lung to crocidolite asbestos. 2. Pulmonary fibrosis after long fibres.
To determine the cellular and fibrogenic responses of the lung to long asbestos fibres, mice were instilled intratracheally with 0.1 mg of a sample of long crocidolite fibres. Animals were killed at intervals to 20 weeks with 3H thymidine injected one h before death. Following bronchoalveolar lavage, an increase in polymorph neutrophils (PMN) and alveolar macrophages (AM) was found during the first week, accompanied by elevated glucosaminidase and alveolar protein levels. Although the PMN number dropped, some were always recovered by lavage to 20 weeks. Early multifocal necrosis of bronchiolar epithelium was followed by a large increase in labelling of epithelial cells and underlying fibroblasts. Epithelial overgrowth of luminal long fibres and inflammatory exudates was followed by giant cell and granuloma formation in the interstitium. After four weeks collagen levels were significantly increased and fibrosis was seen in these peribronchiolar locations. A few small fibres were observed in AM but no evidence of fibrosis was seen in alveolar walls. These findings suggest that injury to bronchial and bronchiolar epithelium allows long fibres to reach the interstitium where subsequent macrophage-fibroblast interactions result in a severe fibrotic reaction that resembles the bronchiolar component of human asbestosis.


The Impact of Selective Fetal Growth Restriction or Birth Weight Discordance on Long-Term Neurodevelopment in Monochorionic Twins: A Systematic Literature Review.
The aim of this review was to assess the impact of selective fetal growth restriction (sFGR) and/or birth weight discordance (BWD) on long-term neurodevelopment in monochorionic (MC) twins. Five out of 28 articles assessed for eligibility were included. One article concluded that the incidence of long-term neurodevelopmental impairment (NDI) was higher in BWD MC twins (11/26, 42%) than in BWD dichorionic (DC) (5/38, 13%) and concordant MC twins (6/71, 8%). BWD MC twins had a 6-fold higher risk of cerebral palsy compared to DC twins (5/26, 19% vs. 1/40, 3%, p < 0.05). Another article described a linear relationship between birth weight and verbal IQ scores, demonstrating a 13-point difference for a 1000 gram BWD between the twins, with a disadvantage for the smaller twin (p < 0.0001). Three articles analyzing within-pair differences showed that the smaller twin more frequently demonstrated mild NDI (6/80, 8% vs. 1/111, 1%) and lower developmental test scores (up to 5.3 points) as opposed to its larger co-twin. Although these results suggest that MC twins with sFGR/BWD are at increased risk of long-term NDI as compared to BWD DC or concordant MC twins, with a within-pair disadvantage for the smaller twin, the overall level of evidence is of moderate quality. As only five articles with a high degree of heterogeneity were available, our review mainly demonstrates the current lack of knowledge of the long-term outcomes of MC twins with sFGR/BWD. Insight into long-term outcomes will lead to improved prognostics, which are essential in parent counseling and crucial in the process of forming a management protocol specifically for twins with sFGR to optimally monitor and support their development.


Allergic contact dermatitis to costus: removal of haptens with polymers.
Costus oil, an iol isolated from a Composite, Saussurea lappa C., used in perfumery, is responsible of numerous cases of allergic contact dermatitis (ACD). The haptens incriminated are sesquiterpene lactones, costunolide and dehydrocostuslactone. These lactones can be removed from the oil by using a polymer, aminoethyl-polystyrene, to which they become bound: the passing solution is lactone-free. A group of guinea-pigs could be successfully sensitized (Freund Complete Adjuvant Test) to costus essential oil, while another group, injected in the same way with polymer-treated essential oil (i.e. lactones) could not be sensitized. This polymer therefore provides a means to render complex plant extracts non-allergic.


Cytoplasmic organelles on the road to mRNA decay.
Localization of both mRNAs and mRNA decay factors to internal membranes of eukaryotic cells provides a means of coordinately regulating mRNAs with common functions as well as coupling organelle function to mRNA turnover. The classic mechanism of mRNA localization to membranes is the signal sequence-dependent targeting of mRNAs encoding membrane and secreted proteins to the cytoplasmic surface of the endoplasmic reticulum. More recently, however, mRNAs encoding proteins with cytosolic or nuclear functions have been found associated with various organelles, in many cases through unknown mechanisms. Furthermore, there are several types of RNA granules, many of which are sites of mRNA degradation; these are frequently found associated with membrane-bound organelles such as endosomes and mitochondria. In this review we summarize recent findings that link organelle function and mRNA localization to mRNA decay. This article is part of a Special Issue entitled: RNA Decay mechanisms.


The relationship between maternal body composition in early pregnancy and foetal mid-thigh soft-tissue thickness in the third trimester in a high-risk obstetric population.
Maternal obesity is an emerging challenge in contemporary obstetrics. To date there has been no study analysing the relationship between specific maternal body composition measurements and foetal soft-tissue measurements. The aim of this study was to determine whether measurement of maternal body composition at booking predicts foetal soft-tissue trajectories in the third trimester. We analysed the relationship between foetal thigh in the third trimester and both maternal BMI and body composition using the Tanita digital scales in the first trimester. Foetal subcutaneous thigh tissue measurements were obtained at intervals of 28, 32 and 36 weeks of gestation. A total of 160 women were identified. There was a direct correlation between MTST at 36 weeks and BMI (p = .002). There was a positive correlation between MTST at 36 weeks and leg fat mass (p = .13) and leg fat free mass (p = .013). There was a positive correlation between arm fat free mass and MTST at 36 weeks. We showed there is an association between maternal fat distribution and foetal subcutaneous thigh tissue measurements. MTST may be more useful in determining if a child is at risk of macrosomia. Impact statement Previous studies have suggested that maternal obesity programmes intrauterine foetal adiposity and growth. The aim of this study was to examine the relationship in a high-risk obstetric population between measurements of maternal body composition in early pregnancy and the assessment of foetal adiposity in the third trimester using serial ultrasound measurements of mid-thigh soft-tissue thickness. BMI is only a surrogate measurement of fat and does not measure fat distribution. Our study shows the distribution of both maternal fat and fat-free mass in early pregnancy may be positively associated with foetal soft-tissue measurements in the third trimester. Maternal arthropometric measurements other than BMI may help predict babies at risk of macrosomia and neonatal adiposity.


Effect of preoperative administration of intravenous paracetamol during cesarean surgery on hemodynamic variables relative to intubation, postoperative pain and neonatal apgar.
Selection of anesthetic drugs for cesarean section requires many considerations. Anesthetic drugs for this purpose must prevent hemodynamic stress due to tracheal intubation, while inducing neonatal complications. This study was conducted to determine the effects of paracetamol given before induction of anesthesia on cardiovascular responses to tracheal intubation and postoperative pain in the mother, and on neonatal Apgar score. This double-blind randomized placebo-controlled trial included 60 women in ASA I, without underlying diseases and fetal distress, who were candidates for elective cesarean section under general anesthesia. Patients were divided into two groups of 30 patients. Patients in the paracetamol group received 1 g intravenous (IV) paracetamol 20 min before the operation, while those in the placebo group received 1 cc normal saline at the same time. In both groups, anesthesia was induced by sodium thiopental and succinylcholine. Maternal systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were measured before and immediately upon induction of anesthesia, and at first and fifth minute after tracheal intubation. Neonatal effects were assessed by Apgar score. Postoperative pain was assessed by use of the visual analog scale (VAS). The dose of analgesic used and the time of the first analgesic request by patients postoperatively were recorded. The SBP, DBP, MAP and HR were controlled significantly better in paracetamol group than in placebo group (P < 0.05). The mean 1-min and 5-min Apgar scores of neonates did not differ between the groups. The VAS pain score was significantly lower in paracetamol group than in placebo group at all measuring times (P < 0.05). Also, paracetamol caused later first analgesic request and lower dose of analgesic needed to control pain postoperatively (P < 0.05). In conclusion, the results of our study suggested IV paracetamol to be an efficacious agent to decrease hemodynamic responses to tracheal intubation, while providing better postoperative pain management without considerable neonatal complications in women undergoing cesarean section in general anesthesia.


Recent Advances on Graphene Quantum Dots as Multifunctional Nanoplatforms for Cancer Treatment.
Graphene quantum dots (GQDs), the latest member of the graphene family, have attracted enormous interest in the last few years, due to their exceptional physical, chemical, electrical, optical, and biological properties. Their strong size-dependent photoluminescence and the presence of many reactive groups on the graphene surface allow their multimodal conjugation with therapeutic agents, targeting ligands, polymers, light responsive agents, fluorescent dyes, and functional nanoparticles, making them valuable agents for cancer diagnosis and treatment. In this review, the very recent advances covering the last 3 years on the applications of GQDs as drug delivery systems and theranostic tools for anticancer therapy are discussed, highlighting the relevant factors which regulate their biocompatibility. Among these factors, the size, kind, and degree of surface functionalization have shown to greatly affect their use in biological systems. Toxicity issues, which still represent an open challenge for the clinical development of GQDs based therapeutic agents, are also discussed at cellular and animal levels.


Role of Streptococcus pneumoniae Proteins in Evasion of Complement-Mediated Immunity.
The complement system plays a central role in immune defense against Streptococcus pneumoniae. In order to evade complement attack, pneumococci have evolved a number of mechanisms that limit complement mediated opsonization and subsequent phagocytosis. This review focuses on the strategies employed by pneumococci to circumvent complement mediated immunity, both in vitro and in vivo. At last, since many of the proteins involved in interactions with complement components are vaccine candidates in different stages of validation, we explore the use of these antigens alone or in combination, as potential vaccine approaches that aim at elimination or drastic reduction in the ability of this bacterium to evade complement.


Reconstruction of Thoracic Spine Using a Personalized 3D-Printed Vertebral Body in Adolescent with T9 Primary Bone Tumor.
Neurosurgery and spine surgery have the potential to benefit from the use of 3-dimensional printing (3DP) technology due to complex anatomic considerations and the delicate nature of surrounding structures. We report a procedure that uses a 3D-printed titanium T9 vertebral body implant post T9 vertebrectomy for a primary bone tumor. A 14-year-old female presented with progressive kyphoscoliosis and a pathologic fracture of the T9 vertebra with sagittal and coronal deformity due to a destructive primary bone tumor. Surgical resection and reconstruction was performed in combination with a 3D-printed, patient-specific implant. Custom design features included porous titanium end plates, corrective angulation of the implant to restore sagittal balance, and pedicle screw holes in the 3D implant to assist with insertion of the device. In addition, attachment of the anterior column construct to the posterior pedicle screw construct was possible due to the customized features of the patient-specific implant. An advantage of 3DP is the ability to manufacture patient-specific implants, as in the current case example. Additionally, the use of 3DP has been able to reduce operative time significantly. Surgical procedures can be preplanned using 3DP patient-specific models. Surgeons can train before performing complex procedures, which enhances their presurgical planning in order to maximize patient outcomes. When considering implants and prostheses, the use of 3DP allows a superior anatomic fit for the patient, with the potential to improve restoration of anatomy.


Cutting Edge: CD3 ITAM Diversity Is Required for Optimal TCR Signaling and Thymocyte Development.
For the αβ or γδTCR chains to integrate extracellular stimuli into the appropriate intracellular cellular response, they must use the 10 ITAMs found within the CD3 subunits (CD3γε, CD3δε, and ζζ) of the TCR signaling complex. However, it remains unclear whether each specific ITAM sequence of the individual subunit (γεδζ) is required for thymocyte development or whether any particular CD3 ITAM motif is sufficient. In this article, we show that mice utilizing a single ITAM sequence (γ, ε, δ, ζa, ζb, or ζc) at each of the 10 ITAM locations exhibit a substantial reduction in thymic cellularity and limited CD4-CD8- (double-negative) to CD4+CD8+ (double-positive) maturation because of low TCR expression and signaling. Together, the data suggest that ITAM sequence diversity is required for optimal TCR signal transduction and subsequent T cell maturation.


[Variability of short tandem repeats on the human Y chromosome].
Nine rare (biallelic) mutations and six short tandem repeats (STR) mapping to the nonrecombining portion of the Y chromosome were genotyped in 734 males from different geographical regions inhabited by the contemporary Armenian population. The analysis of molecular variance (AMOVA) showed that 48.9% of total STR genetic variation was explained by the differences between the haplogroups isolated based on biallelic polymorphism, whereas only 1.3% of genetic variation could be attributed to the differences between the geographic groups.


To shield or not to shield: application of bismuth breast shields.
The purposes of this essay are to describe the effects of bismuth breast shielding on radiation exposure of the breast and posterior chest wall and to present arguments for and against the use of breast shields. Breast tissue may receive substantial radiation doses during CT examinations. Bismuth shields effectively reduce breast exposure at the expense of increased noise and artifacts. Because bismuth shields reduce radiation transmission in all directions, posterior-to-anterior irradiation results in wasted exposure of posterior tissues. Similar breast radiation reductions can be achieved without shielding by globally reducing tube current. In general, more advanced methods of reducing exposure, including dose modulation and iterative reconstruction techniques, are superior if available.


Giant Thrombosis at Left Anterior Descending Artery Aneurysm in a 10-Year Old Boy with Granulomatosis with Polyangiitis.
Granulomatosis with polyangiitis (GPA), necrotizing vasculitis of small and medium-sized vessels, is traditionally believed to mainly affect respiratory tract with additional focal kidney involvements as its primary manifestations with a relatively rare annual incidence rate of 20-50 cases per million. Six percent of the affected cases have cardiac involvements; among which, aneurysms comprise the lowest penetrance. By this paper, we aim to cast light on clinical diagnostic and treatment methods of a rare case presentation, a 10-year-old male GPA patient, diagnosed with massive thrombosis at his coronary artery aneurysm. GPA should be considered as differential diagnosis of prolong fever and coronary aneurysms in adolescents.


Isolation of rat serum alpha 1-microglobulin. Identification of a complex with alpha 1-inhibitor-3, a rat alpha 2-macroglobulin homologue.
Alpha 1-Microglobulin (alpha 1-m), or protein HC, a low molecular weight plasma protein with immunoregulatory properties, was isolated from rat serum by affinity chromatography using Sepharose-coupled monoclonal anti-alpha 1-m antibodies. High molecular weight forms of alpha 1-m were then separated from the low molecular weight alpha 1-m by gel chromatography of the eluted proteins. The apparent Mr (28,000), the charge heterogeneity, the N-linked carbohydrate, and yellow-brown chromophore suggest that the low molecular weight alpha 1-m is the serum counterpart to urinary alpha 1-m, which was purified previously. A high molecular weight complex of alpha 1-m was also isolated by the gel chromatography. It was homogeneous as judged by nondenaturing polyacrylamide gel electrophoresis. The molecule was bound by antibodies against human alpha 2-macroglobulin, and experiments with antisera against the three alpha-macroglobulin variants in rat serum, alpha 1-macroglobulin, alpha 2-macroglobulin, and alpha 1-inhibitor-3 (alpha 1I3) suggested that alpha 1I3 was the complex-partner of alpha 1-m. An antiserum raised against high molecular weight alpha 1-m was then used to isolate the complex-partner of alpha 1-m from rat serum with affinity chromatography, and this molecule was positively identified as alpha 1I3 by its physicochemical properties. Gel chromatography of the alpha 1I3.alpha 1-m complex suggested a molecule with an Mr of 266,000. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, however, it migrated as three major molecular species with apparent molecular weights of 224,000, 205,000, and 194,000 and several minor species of both higher and lower molecular weights, suggesting a complex subunit structure. alpha 1-m and alpha 1I3 could be detected in all three major species by Western blotting, and NH2-terminal amino acid sequencing suggested a molar ratio of 1:1 of alpha 1-m and alpha 1I3 in all three species. alpha 1I3.alpha 1-m was colorless, did not show light absorbance beyond 300 nm which is typical of low molecular weight alpha 1-m and was electrophoretically homogeneous, suggesting that it lacks the chromophore. Finally, the serum concentrations of the alpha 1I3.alpha 1-m complex and free alpha 1-m were determined as 0.16 and 0.010 g/liter, respectively. Thus, alpha 1I3.alpha 1-m constitutes 1-3% of the total alpha 1I3 in rat serum (w/w) and approximately 60% of the total alpha 1-m.


Plant vermicides of Haitian Vodou show in vitro activity against larval hookworm.
Haitian Vodou priests (houngans) and priestesses (mambos) use plant remedies to treat many illnesses, including intestinal parasite infections. The present study screened 12 plants used in Vodou treatments for intestinal parasites to detect in vitro activity against infective-stage larvae of the hookworm Ancylostoma caninum. Water-soluble extracts of 4 of the 12 plants inhibited serum-stimulated feeding by larval A. caninum in a dose-dependent manner. All 4 plant extracts inhibited feeding induced by the muscarinic agonist arecoline, suggesting that these plant extracts may inhibit the insulin-like signaling pathway involved in the recovery and resumption of development of arrested A. caninum larvae. These results indicate that at least some of the plants used in traditional Haitian medicine as vermifuges show activity against nematode physiological processes.


Facile Approaches to Phosphorescent Bis(cyclometalated) Pentafluorophenyl PtIV Complexes: Photophysics and Computational Studies.
A convenient and general strategy for the synthesis of stable bis(cyclometalated) pentafluorophenyl PtIV complexes fac-[Pt(C^N)2 (C6 F5 )Cl] (3 a-f) and mer-[Pt(C^N)2 (C6 F5 )(CN)] (4 c,d) has been developed. Complexes 3 were selectively generated by low-temperature oxidation of the cyclometalated PtII complexes [Pt(C^N)(HC^N)(C6 F5 )] 2 [prepared from cis-[Pt(C6 F5 )2 (HC^N)2 ] (1) intermediates] with PhICl2 and subsequent metalation of the pendant HC^N ligand. Complexes 3 a,b were also alternatively generated by irradiation (Hg lamp, 400 W) of complexes 2 a,b, respectively, in CH2 Cl2 . This latter reaction proceeds via the hydride PtIV species cis-[Pt(C^N)2 (C6 F5 )H], detected as the only intermediate species. The molecular structures of 1 a,d, 2 a, and 3 a,b,d,e were confirmed by X-ray diffraction. The substitution of Cl- by CN- in fac-[Pt(C^N)2 (C6 F5 )Cl] [C^N=2-phenylbenzothiazole (3 c), 2-(4-bromophenyl)benzothiazole (3 d)] evolved with isomerization to give rise to the isomers (OC-6-42)-[Pt(C^N)2 (C6 F5 )(CN)] (4 c, 4 d) having a mer disposition of the cyclometalated and C6 F5 groups (X-ray, 4 c). All the complexes are luminescent and their electronic spectra have been compared and interpreted with the aid of time-dependent DFT calculations.


Electronic properties of star-shaped oligofluorenes containing an isotruxene core: interplay of para and ortho conjugation effects in phenylene-based pi systems.
The synthesis, photophysics, cyclic voltammetry, spectroelectrochemistry, and electrogenerated chemiluminescence (ECL) properties of a series of unsymmetrical star-shaped oligophenylenes IT1-IT4 are reported. The electronic couplings among the three oligofluorene arms in IT1-IT4 are strong due to the para-ortho branched isotruxene core. The ortho conjugation effect results in band splitting in the absorption spectra for both the neutral and the radical ionic form with a stronger effect for the latter. However, such an ortho conjugation effect becomes weaker as the oligofluorene arms are longer. The same fluorescence maxima displayed by IT2-IT4 suggest that the exciton coherence size (or the bound electron-hole pair) is no larger than 16 phenylene rings. The little chain-length dependence of the first reduction and oxidation potentials for IT1-IT4 suggests that the reversible electron-transfer processes of the neutral species are mainly associated with the isotruxene core. The ECL of IT1-IT4 is from the singlet excited state, but the spectra are red shifted with respect to the fluorescence spectra of dilute solutions due to the reabsorption effect. Our results also reveal that the meta conjugation interactions in the previously reported C 3-symmetrical truxene-oligofluorene analogs T1-T4 (Kanibolotsky, A. L.; Berridge, R.; Skabara, P. J.; Perepichka, I. F.; Bradley, D. D. C.; Koeberg, M. J. Am. Chem. Soc. 2004, 126, 13695-13702) are rather weak.


Development of a Novel Tablet-based Approach to Reduce HIV Stigma among Healthcare Staff in India.
Although stigma is considered to be one of the major barriers to reducing the AIDS epidemic in India, efforts to reduce stigma have not been sufficiently examined. In response, a partially computer-administered three-session stigma reduction intervention was developed and is currently being tested. This paper describes the technological design, development, implementation, and management of these in-person tablet-administered assessment and intervention sessions that are being used to evaluate the efficacy of this innovative stigma reduction intervention among nursing students and ward attendants in India.


[Design and development of controlled release of drugs from injectable microcapsules].
Monolithic microcapsules were designed and developed for controlled release of leuprorelin for one month following a single injection. Copoly (DL-lactic/glycolic) acid (PLGA) of copolymer ratio of 75/25 and average molecular weight of 14,000 was suitable for achieving steady serum leuprorelin levels in rats and dogs for 4 weeks. The clinical efficacy of these injectable microcapsules of leuprorelin has been widely proved for prostate cancer, endometriosis, and other sex hormone dependent diseases in about sixty countries. The interaction between the basic functional group of the drug and the carboxylic end group of PLGA was found to be the most important factor in preparing the microcapsules with a small initial burst, as shown with thyrotropin releasing hormone (TRH) and a water-soluble GPIIb/IIIa antagonist (TAK-029).


[Effects of interim hemodialysis on survival and clinical outcomes in patients with maintenance peritoneal dialysis].
To investigate the effects of interim hemodialysis (HD) on survival and clinical outcomes in patients with maintenance peritoneal dialysis (PD). The clinical data of 908 patients undergoing maintenance PD from January 2010 to December 2014 registered in Zhejiang Dialysis Regisration System were retrospectively analyzed. Among all PD patients, 176 cases received interim HD for less than 3 months, and then transferred to PD (transfer group) and 732 cases had initial PD (non-transfer group). The demographic parameters, biochemical data, comorbidity, details of peritonitis and transplantation were documented. Survival curves were made by the Kaplan-Meier method; univariate and multivariate analyses were performed with Cox proportional hazard regression model to identify risk factors of mortality. Compared with patients in transfer group, patients in non-transfer group had significantly higher serum albumin and total Kt/V levels. The survival rate was significantly higher in non-transfer group, but there was no significant difference in technique survival between two groups. After multivariable adjustment, initial dialysis modality (HR=1.60, 95% CI: 1.01~2.56), age (HR=1.07, 95% CI:1.05~1.09) and serum albumin (HR=0.96, 95% CI: 0.93~0.99) and Charslon comorbidity index (HR=2.54, 95% CI:1.63~3.94) were independent factors for long-term survival. Patients who transfer to PD after interim HD have lower survival rate than patients who start with and are maintained on PD. HD is an independent risk factor for PD patients, therefore, patients with PD should be well informed and educated with dialysis protocols.


High tumor mutation burden predicts favorable outcome among patients with aggressive histological subtypes of lung adenocarcinoma: A population-based single-institution study.
Tumor mutation burden (TMB) is an emerging predictive cancer biomarker. Few studies have addressed the prognostic role of TMB in non-small cell lung carcinoma, with conflicting results. Moreover, the association of TMB with different histological subtypes of lung adenocarcinoma has hitherto not been systematically evaluated. Here we studied the prognostic value of TMB and its distribution in different histological subtypes of lung adenocarcinomas in a retrospective cohort using the most recent updated classification guidelines. 176 surgically resected stage I-IV lung adenocarcinomas were histologically reclassified according to WHO 2015 guidelines. A modified classification subdividing the acinar subtype into classic acinar, complex glandular and cribriform subtypes was further applied and potentially prognostic histopathological characteristics such as tumor-infiltrating lymphocytes were evaluated. 148 patients with stage I-III tumors and complete follow-up data were included in the survival analyses. TMB was determined by a commercial next generation sequencing panel from 131 tumors, out of which 105 had survival data available. Predominant micropapillary, solid and complex glandular as well as nonpredominant cribriform histological subtypes were associated with significantly shorter survival. High TMB concentrated in micropapillary, solid and acinar predominant subtypes. Interestingly, TMB ≥ 14 mutations/MB conferred a stage- and histology-independent survival benefit compared to TMB < 14 in multivariable analysis for overall (HR 0.284, 95% CI 0.14-0.59, P=0.001) and disease-specific survival (HR 0.213, 95% CI 0.08-0.56, P=0.002). TMB was an independent biomarker of favorable prognosis in our cohort of lung adenocarcinoma despite being associated with predominant histological subtypes considered aggressive.


Towards the Investigation of the Adaptive Divergence in a Species of Exceptional Ecological Plasticity: Chromosome-Scale Genome Assembly of Chouardia litardierei (Hyacinthaceae).
One of the central goals of evolutionary biology is to understand the genomic basis of adaptive divergence. Different aspects of evolutionary processes should be studied through genome-wide approaches, therefore maximizing the investigated genomic space. However, in-depth genome-scale analyses often are restricted to a model or economically important species and their closely related wild congeners with available reference genomes. Here, we present the high-quality chromosome-level genome assembly of Chouardia litardierei, a plant species with exceptional ecological plasticity. By combining PacBio and Hi-C sequencing technologies, we generated a 3.7 Gbp genome with a scaffold N50 size of 210 Mbp. Over 80% of the genome comprised repetitive elements, among which the LTR retrotransposons prevailed. Approximately 86% of the 27,257 predicted genes were functionally annotated using public databases. For the comparative analysis of different ecotypes' genomes, the whole-genome sequencing of two individuals, each from a distinct ecotype, was performed. The detected above-average SNP density within coding regions suggests increased adaptive divergence-related mutation rates, therefore confirming the assumed divergence processes within the group. The constructed genome presents an invaluable resource for future research activities oriented toward the investigation of the genetics underlying the adaptive divergence that is likely unfolding among the studied species' ecotypes.


Improving general practitioner records in France by a two-round medical audit.
The effectiveness of clinical audits in changing the practice of health care professionals is a moot point. Methods of implementation impinge directly upon outcomes. We investigated whether a network of local opinion leaders could contribute towards a successful audit. Our objectives were to: (i) bring about an improvement in record keeping in general practice; and (ii) increase GPs awareness of medical evaluation. The GPs were recruited by local opinion leaders who had been briefed by the French National Agency for Accreditation and Evaluation in Health Care (ANAES, formerly ANDEM). On a given day (first round of the audit) they were invited to examine whether the medical records of their 10 first patients met 13 set criteria. Overall results were analysed by ANAES. Each GP was informed of how well they had fared compared with the regional and national averages and was provided with a standard set of recommendations. Anonymity was ensured by the local leaders. A second round was conducted 6 months later. A total of 244 GPs took part in both rounds of the audit; 32 dropped out after the first round. Their results were of a significantly lower standard. A significant improvement in results (P<0.025) was recorded between the two rounds for all 13 criteria of the questionnaire. Overall scores improved between the two rounds for 69 of the GPs and improved above average for 49. The greatest scatter in results was noted for items relating to medical history rather than to personal identity (administrative data). Self-assessment can help improve general standards of medical record keeping. A network of local opinion leaders, briefed by a national agency whose mission is to promote quality improvement in health care, seems to be an effective means of inducing participation in self-assessment.


Space radiation does not induce a significant increase of intrachromosomal exchanges in astronauts' lymphocytes.
Chromosome aberration analysis in astronauts has been used to provide direct, biologically motivated estimates of equivalent doses and risk associated to cosmic radiation exposure during space flight. However, the past studies concentrated on measurements of dicentrics and translocations, while chromosome intrachanges (inversions) have never been measured in astronauts' samples. Recent data reported in the literature suggest that densely ionizing radiation can induce a large fraction of intrachanges, thus leading to the suspicion that interchanges grossly underestimate the cosmic radiation-induced cytogenetic damage in astronauts. We have analyzed peripheral blood lymphocytes from 11 astronauts involved in short- or long-term space flights in low-Earth orbit using high-resolution multicolor banding to assess the frequency of intrachromosomal exchanges in both pre- and post-flight samples. We did not detect any inversions in chromosome 5 from a total of 2800 cells in astronauts' blood. In addition, no complex type exchanges were found in a total of 3590 astronauts' lymphocytes analyzed by multifluor fluorescence in situ hybridisation. We conclude that, within the statistical power of this study, the analysis of interchanges for biological dosimetry in astronauts does not significantly underestimate the space radiation-induced cytogenetic damage, and complex-type exchanges or intrachanges have limited practical use for biodosimetry at very low doses.


Variation in dermcidin expression in a range of primary human tumours and in hypoxic/oxidatively stressed human cell lines.
Dermcidin acts as a survival factor in a variety of cancer cell lines under hypoxia or oxidative stress. The aim of this study was to evaluate dermcidin expression in cell lines following simulation of tumour microenvironmental conditions and in a range of primary tumours. Tumour tissues were collected from patients with oesophageal (28 samples), gastric (20), pancreatic (five), bile duct (one) and prostatic (52) carcinomas as well as 30 benign tissue samples, for assessment of dermcidin mRNA levels using real-time PCR. Dermcidin expression was assessed in prostatic and pancreatic cancer cell lines, with and without induction of hypoxia or oxidative stress. Dermcidin mRNA expression was very low or absent in both unstressed and stressed prostate cell lines. None of the primary prostate tissue, benign or malignant, expressed dermcidin mRNA. Only two (4%) of the gastro-oesophageal cancer samples expressed moderate quantities of dermcidin mRNA. However, three (60%) of the pancreatic cancer samples and the single cholangiocarcinoma specimen had moderate/high levels of dermcidin expression. Of the two pancreatic cancer cell lines, one expressed dermcidin moderately but neither showed a response to hypoxia or oxidative stress. Expression of dermcidin in human primary tumours appears highly variable and is not induced substantially by hypoxia/oxidative stress in cell line model systems. The relationship of these findings to dermcidin protein levels and cell survival remains to be determined.


[The ABCs of transfusion for hematologists].
"Guidelines for the use of red blood cell products, platelet transfusion concentrates and fresh frozen plasma based on scientific evidence" was published by the Japan Society of Transfusion Medicine and Cell Therapy. Each transfused blood product carries a certain risk of an acute or late adverse event. Hematologists must be familiar with transfusion-associated adverse events, such as transfusion-related acute lung injury, transfusion-associated circulatory overload, post-transfusion graft-versus-host disease, transfusion-transmitted viral infection, etc. Thus, these guidelines should be followed for the appropriate use of blood products according to trigger values and indications for transfusion.


Characterization of an acrosomal matrix protein in hamster and bovine spermatids and spermatozoa.
Experiments have been carried out characterizing an Mr 22,000 protein present in the acrosomes of hamster and bull spermatozoa. The Mr 22,000 protein is resistant to solubilization in detergent solutions containing high or low salt and has a pI of -5.2. With various lectins, the protein from hamster sperm was shown to be sparingly glycosylated with N-acetylglucosamine, mannose, and galactose while that from the bull demonstrated a slight reactivity for galactose. Using a specific monoclonal antibody (MAB 4/18), the Mr 22,000 polypeptide has been localized exclusively to the acrosomes of mature testicular and epididymal hamster and bovine sperm. Acrosomal components of differentiating bovine and hamster spermatids in tissue sections did not react with the monoclonal antibody, although the protein was present in immunoblots of round spermatids. In bovine sperm, MAB 4/18-staining at the ultrastructural level with immunogold-labeled second antibody was present as a reticulum throughout the acrosomal cap and as punctate aggregates in the equatorial segment. In hamster sperm, MAB 4/18-reactivity was present along the periphery of the acrosome in conjunction with matrix components (M1 and M2), as well as along the inner acrosomal membrane. These observations indicate that the acrosomes of bovine and hamster sperm possess an immunologically related Mr 22,000 protein and suggest that differences in MAB 4/18-staining of spermatids and spermatozoa is a result of epitope modification and/or a change in accessibility of the epitope to the antibody probe during the course of spermiogenesis. Based on its localization and solubility properties, we suggest that the Mr 22,000 protein, in conjunction with other polypeptides, forms a structural framework to maintain acrosomal shape and/or compartmentalize acrosomal contents.


SAW synchronous multimode resonator with gold electrodes on quartz.
A surface acoustic wave synchronous multimode resonator with gold electrodes on ST-cut quartz was designed, fabricated, and measured. At a frequency of about 194.3 MHz, an insertion loss of about 14 dB, and loaded and unloaded quality factors of 11,500 and 14,500, respectively, were obtained.


Associations between long-term averages of metabolic parameters in adulthood and cardiac structure and function in later life.
The effects of long-term levels of body mass index (BMI), blood pressure (BP), plasma lipids and fasting blood glucose (FBG) on the cardiac structure and function in later life in general population are to evaluate. We included adult participants without heart failure from Framingham Heart Study. The respective averages over a span of 30-36 years of seven parameters were pooled into linear regression models simultaneously to evaluate their associations with subsequent left atrial internal dimension (LAID), left ventricular mass index (LVMi), internal dimension (LVID), ejection fraction (LVEF), global longitudinal strain (GLS) and mitral inflow velocity to early diastolic mitral annular velocity (E/é). In 1838 participants (56.0% female, mean age 66.1 years), per 1-standard deviation (SD) increment of mean BMI correlated with larger LAID and LVID (β 0.05~0.17, standard error [SE] 0.01 for all), greater LVMi (β [SE], 1.49 [0.46]), worse E/é (β [SE], 0.28 [0.05]). Per 1-SD increment of mean systolic BP correlated with greater LVMi (β [SE], 4.70 [0.69]), LVEF (β [SE], 0.73 [0.24]), E/é (β [SE], 0.52 [0.08]), whereas increase of mean diastolic BP correlated with smaller LVMi (β [SE], -1.61 [0.62]), LVEF (β [SE], -0.46 [0.22]), E/é (β [SE], -0.30 [0.07]). Per 1-SD increment of mean high density lipoprotein cholesterol (HDL-c) correlated with smaller LVID (β [SE], -0.03 [0.01]) and better systolic function (LVEF, β [SE], 0.63 [0.19]; GLS, β [SE], -0.20 [0.10]). The variabilities of BMI, BP and HDL-c also correlated with certain cardiac measurements. In long-term, BMI affected the size and mass of heart chambers, systolic and diastolic BP differently influenced left ventricular mass and function, higher HDL-c linked to better systolic function. Clinical trial registration: URL: https://clinicaltrials.gov . Identifier: NCT00005121.


Melatonin prevents sleep deprivation-associated anxiety-like behavior in rats: role of oxidative stress and balance between GABAergic and glutamatergic transmission.
Sleep deprivation (SD) has been shown to induce anxiety-like behavior. Melatonin, an endogenous potent antioxidant, protects neurons from oxidative stress in many disease models. Here we investigated the effect of melatonin against SD-induced anxiety-like behavior and attempted to define the possible mechanisms involved. SD was induced in rats using modified multiple platform model. Melatonin (15 mg/kg) was administered to the rats via intraperitoneal injection. The elevated plus maze test, open field test and light-dark exploration were used to evaluate anxiety-like behavior. Serum corticosterone was measured to determine stress level. Malondialdehyde (MDA) level and superoxide dismutase (SOD) enzyme activity of amygdala and serum were performed to determine the level of oxidative stress. Levels of protein were detected by means of Western blot. The results showed that SD induces anxiety-like behavior, while melatonin treatment prevented these changes. Serum corticosterone also increased with SD but its levels were normalized by melatonin. In addition, melatonin reversed SD-induced changes in MDA and SOD in both of amygdala and serum. The results of Western blot showed that melatonin attenuated the up-regulation of NR2B-containing N-methyl-D-aspartate receptors, GluR1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor as well as phosphorylation of GluR1 at Ser831, and Ca2+/calmodulin-dependent protein kinase II-alpha in SD rats. Meanwhile, melatonin blocked the down-regulation of γ-aminobutyric acid A-alpha-2 receptor. In conclusion, our results suggest that melatonin prevents anxiety-like behavior induced by SD. The possible mechanism may be attributed to its ability to reduce oxidative stress and maintain balance between GABAergic and glutamatergic transmission.


Neurological complications and surgical outcome in patients with anterior choroidal segment aneurysms.
Choroidal segment aneurysms occur in close relation to terminal internal carotid branches and concomitant anatomical variations in the anterior choroidal artery. The authors evaluate the demographics, presentation, operative techniques, and surgical outcome in 13 patients with this aneurysm. After identifying the study group from a retrospective review of all supraclinoid ICA aneurysms operated in our institution over an 8-year period, analysis was done with respect to the radiological and operative findings and clinical follow-up. Statistical significance for outcome was analyzed using two-tailed Fisher's exact test (p < 0.05). The incidence of choroidal segment aneurysm was 3.02%. Six (46%) patients had Fisher grade III bleed on imaging. Nine (69%) patients had a good surgical outcome. Three patients had ischemic stroke in the anterior choroidal territory. Patient demographics, Hunt and Hess score at presentation, Fisher score on computed tomogram scan, aneurysm characteristics and clip configuration had no bearing on surgical outcome. In patients with anterior choroidal artery aneurysms managed surgically, meticulous surgical exposure, identification of anatomical variations of parent artery, appropriate clip selection and usage of intra-operative Doppler limit ischemic complications, and allay the development of the morbid clinical syndrome associated with anterior choroidal territory infarction.


[Achievements of S. N. Fyodorov's school in the field of keratoplasty and cornea replacement].
Reduction in corneal transparence leading to the loss of sight may be caused by different factors, such as eye burns and injuries, keratitis, corneal ulcers, primary and secondary dystrophy, keratoconus, and keratoglobus. In many cases, keratoplasty presents an effective treatment. S. N. Fyodorov made a great contribution to the development of cornea replacement. This was him who placed the entire ophthalmology, including keratoplasty, at the microsurgical level, suggested the use of large-diameter grafts, and was the initiator of establishing the first Eye Tissue Bank. Perfection of microsurgical technique, selection and protection of the graft, as well as new approaches to pre- and postoperation therapy have provided transparent engrafting in 35 to 95%. Presently, Eye Microsurgery Complex is the only Russian institution where the problem of cornea replacement is being worked out as a scientific and practical issue. Three models of keratoprosthesis have been developed: Fyodorov-Zuyev model for implantation into a burn leukoma, Moroz-Glazko model for implantation into a dystrophic leukoma, and a "grid" for implantation into a leukoma of any etiology.


In-hospital pediatric cardiac arrest in Honduras.
The objective of this study was to analyze the characteristic and the prognostic factors of in-hospital pediatric cardiac arrest (CA) in a public hospital Honduras. A prospective observational study was performed on pediatric in-hospital CA as a part of a multicenter international study. One hundred forty-six children were studied. The primary end point was survival at hospital discharge. Univariate and multivariate logistic regression analyses were performed to assess the influence of each factor on mortality. Cardiac arrest occurred in the emergency department in 66.9%. Respiratory diseases and sepsis were predominant causes of CA. Return of spontaneous circulation was achieved in 60% of patients, and 22.6% survived to hospital discharge. The factors related with mortality were nonrespiratory cause of CA (odds ratio [OR], 2.55; P = 0.045), adrenaline administration (OR, 4.96; P = 0.008), and a duration of cardiopulmonary resuscitation more than 10 minutes (OR, 3.40; P = 0.012). In-hospital CA in children in a developing country has low survival. Patients with nonrespiratory causes and those who need adrenaline administration and prolonged resuscitation had worse prognosis.


Clinical radiosotope investigations in hydrosyringomyelia and myelodysplasia.
Radioisotope ventriculography was applied clinically in myelodysplastic hydromyelia in three groups of patients: two patients with normal ventricles, two with obstructive hydrocephalus, and 16 with myelodysplasia. In the myelodysplastic group, radioassay in one patient demonstrated flow of radioistope down the hydromyelic cavity. Twenty scintigraphic studies on 16 myelodysplastic patients showed hydromyelia was present in all patients with spontaneously compensated hydrocephalus but in none of those with functional ventricular shunts. This relation between the hydromyelia and disordered ventricular hydrodynamics supports the Gardner hypothesis of myelodysplasia. Radioisotope ventriculography appears a safe and useful method of diagnosing hydrosyringomyelia and evaluating treatment by means of ventricular decompression.


Cytokines in Neuropathic Pain and Associated Depression.
Neuropathic pain occurs as a result of lesion or disease affecting the somatosensory nervous system and is present in a diverse set of peripheral and central pathologies such as nerve trauma, diabetic neuropathy, post-herpetic neuralgia, chemotherapy-induced peripheral neuropathy, spinal cord injury and multiple sclerosis. Debilitating symptoms including allodynia, hyperalgesia and spontaneous pain have a substantial negative impact on patients' quality of life. The currently available therapeutic treatments are generally ineffective and characterised by poor response rates. Accumulating evidence suggests that neuroinflammation and cytokine signalling play a critical role in neuropathic pain. Numerous experimental studies have demonstrated that certain pro-inflammatory cytokines are elevated in neuropathic pain conditions, and administration of these cytokines can elicit pain hypersensitivity in the absence of injury or disease. This phenomenon is also apparent in the 'sickness response', which encompasses a broad inflammatory response to disease and injury and involves a series of physiological and behavioural changes including pain hypersensitivity. Interestingly, the 'sickness response' is also similar in nature to some of the defining characteristics of the depressed state of affective disorder. In this review, we explore links that may relate the co-existence of depression in neuropathic pain patients with the activity of cytokines and discuss the role of several key pro-inflammatory and anti-inflammatory cytokines in neuropathic pain.


Perifollicular protrusions--mid-dermal elastolysis.
Mid-dermal elastolysis is a rare peculiar entity clinically characterized by fine wrinkles and perifollicular protrusions that give the skin an aged or peau d'orange appearance. The histopathologic correlate is a bandlike loss of elastic tissue within the mid-dermis.We present a typical case with prominent perifollicular protrusions.


Neurocritical care of patients with central nervous system infections.
Bacterial meningitis and viral encephalitis are life-threatening infections with high mortality rates. Patients who survive these infections often remain permanently disabled. Potential neurologic complications requiring careful attention include impaired consciousness, elevated intracranial pressure (ICP), hydrocephalus, stroke, and seizures. Systemic complications are also common and are frequently the immediate cause of death. The importance of emergent administration of appropriate antimicrobial therapy cannot be overstated, but critical care of these patients should focus not only on treatment of the underlying infection and its immediate complications but also on minimizing secondary brain injury. Given the increasing complexity of the diagnostic and therapeutic modalities available to manage central nervous system (CNS) infections, the involvement of neurocritical care units and neurointensivists may be particularly helpful in improving outcomes. It is our opinion that ICP measurement should be strongly considered in selected patients with CNS infections, particularly those who are comatose. Treatments for intracranial hypertension, specifically in the setting of CNS infection, are described in this paper. For bacterial meningitis, intravenous dexamethasone should be administered, beginning concomitantly with the initial dose of antibiotics, at least until Streptococcus pneumoniae can be excluded as a pathogen. Clinicians should maintain a high index of suspicion for nonconvulsive seizures. Deterioration in neurologic status should also prompt early use of CT or magnetic resonance angiography and venography to exclude cerebrovascular complications.


Selection of Yeasts as Starter Cultures for Table Olives: A Step-by-Step Procedure.
The selection of yeasts intended as starters for table olives is a complex process, including a characterization step at laboratory level and a validation at lab level and factory-scale. The characterization at lab level deals with the assessment of some technological traits (growth under different temperatures and at alkaline pHs, effect of salt, and for probiotic strains the resistance to preservatives), enzymatic activities, and some new functional properties (probiotic traits, production of vitamin B-complex, biological debittering). The paper reports on these traits, focusing both on their theoretical implications and lab protocols; moreover, there are some details on predictive microbiology for yeasts of table olives and on the use of multivariate approaches to select suitable starters.


Conditions for collection of serum samples for the measurement of fibrin(ogen) degradation products by radioimmunoassay of fragment E.
A number of conditions have been assessed for the collection of serum samples for the measurement of fibrin(ogen) degradation products using a radioimmunoassay for degradation fragment E, which permits precise quantitation of differences. Blood should be collected using minimal venous occlusion into glass tubes containing 10 mg/ml of epsilon amino caproic acid and allowed to clot at 4 to 20 degrees C for at least 4 hours before centrifugation. The serum may be stored at 4 or -20 degrees C. Samples from patients receiving anticoagulant therapy should be treated with 10 IU of thrombin per ml.


Schizophrenia.
The lifetime prevalence of schizophrenia is approximately 0.7% and incidence rates vary between 7.7 and 43.0 per 100,000; about 75% of people have relapses and continued disability, and one third fail to respond to standard treatment. Positive symptoms include auditory hallucinations, delusions, and thought disorder. Negative symptoms (demotivation, self-neglect, and reduced emotion) have not been consistently improved by any treatment. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for positive, negative, or cognitive symptoms of schizophrenia? What are the effects of drug treatments in people with schizophrenia who are resistant to standard antipsychotic drugs? What are the effects of interventions to improve adherence to antipsychotic medication in people with schizophrenia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 51 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review, we present information relating to the effectiveness and safety of the following interventions: amisulpride, chlorpromazine, clozapine, depot haloperidol decanoate, haloperidol, olanzapine, pimozide, quetiapine, risperidone, sulpiride, ziprasidone, zotepine, aripiprazole, sertindole, paliperidone, flupentixol, depot flupentixol decanoate, zuclopenthixol, depot zuclopenthixol decanoate, behavioural therapy, clozapine, compliance therapy, first-generation antipsychotic drugs in treatment-resistant people, multiple-session family interventions, psychoeducational interventions, and second-generation antipsychotic drugs in treatment-resistant people.


Positive predictive value of ICD-9-CM codes to detect acute exacerbation of COPD in the emergency department.
Accurate identification of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) visits by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes will help organizations monitor quality of care for this common condition. A study was undertaken to validate ICD-9-CM coding for accurate identification of AECOPD visits. In a retrospective cohort study at two academic emergency departments (EDs) from July 2005 to June 2006, ICD-9-CM codes 491.2x (obstructive chronic bronchitis), 492.8 (other emphysema), and 496 (chronic airway obstruction, not elsewhere classified) in the principal diagnosis field were used to identify AECOPD visits. A random sample of 100 visits by patients age > or = 55 years of age was selected at each institution, and cases were confirmed by chart review consensus by two emergency physicians. The case definition for AECOPD was current respiratory infection, change in cough, or change in sputum in a patient with physician-diagnosed COPD. On the basis of the selection criteria, 644 eligible visits were identified during the study period, and detailed chart review was performed for 200 randomly selected visits. Patients had a median age of 71 years, 50% were female, and 79% were white. Some 193 (97%) of the visits were confirmed to meet the case definition for AECOPD. Most cases were identified with the code 491.2x. All but one of the false positives were coded as 496, presumably because of lack of another billable diagnosis for these visits. In the first known chart validation of ICD-9-CM codes for identification of AECOPD visits, the proposed ICD-9-CM codes accurately identified cases of AECOPD in the ED. The study contributed to the use of these codes in the National Committee for Quality Assurance's new quality indicator for management of AECOPD.


Approaching MALDI molecular imaging for clinical proteomic research: current state and fields of application.
MALDI imaging mass spectrometry ('MALDI imaging') is an increasingly recognized technique for biomarker research. After years of method development in the scientific community, the technique is now increasingly applied in clinical research. In this article, we discuss the use of MALDI imaging in clinical proteomics and put it in context with classical proteomics techniques. We also highlight a number of upcoming challenges for personalized medicine, development of targeted therapies and diagnostic molecular pathology where MALDI imaging could help.


Glucagon and primary hyperlipidemias.
A reduction in glucagon secretion was found in a number of patients suffering from primary hyperlipidemias. This could be important in both the pathogenesis and classification of hyperlipidemias.


Langmuir probe measurements in a time-fluctuating-highly ionized non-equilibrium cutting arc: analysis of the electron retarding part of the time-averaged current-voltage characteristic of the probe.
This work describes the application of Langmuir probe diagnostics to the measurement of the electron temperature in a time-fluctuating-highly ionized, non-equilibrium cutting arc. The electron retarding part of the time-averaged current-voltage characteristic of the probe was analysed, assuming that the standard exponential expression describing the electron current to the probe in collision-free plasmas can be applied under the investigated conditions. A procedure is described which allows the determination of the errors introduced in time-averaged probe data due to small-amplitude plasma fluctuations. It was found that the experimental points can be gathered into two well defined groups allowing defining two quite different averaged electron temperature values. In the low-current region the averaged characteristic was not significantly disturbed by the fluctuations and can reliably be used to obtain the actual value of the averaged electron temperature. In particular, an averaged electron temperature of 0.98 ± 0.07 eV (= 11400 ± 800 K) was found for the central core of the arc (30 A) at 3.5 mm downstream from the nozzle exit. This average included not only a time-average over the time fluctuations but also a spatial-average along the probe collecting length. The fitting of the high-current region of the characteristic using such electron temperature value together with the corrections given by the fluctuation analysis showed a relevant departure of local thermal equilibrium in the arc core.


Prolonged T cell - DC macro-clustering within lymph node microenvironments initiates Th2 cell differentiation in a site-specific manner.
Formation of T helper 2 (Th2) responses has been attributed to low-grade T cell stimulation, yet how large-scale polyclonal Th2 responses are generated in vivo remains unclear. Here, we used quantitative imaging to investigate early Th2 differentiation within lymph nodes (LNs) following cutaneous allergen administration. Contrary to current models, Th2 differentiation was associated with enhanced T cell activation and extensive integrin-dependent 'macro-clustering' at the T-B border, which also contrasted clustering behavior seen during Th1 differentiation. Unexpectedly, formation of Th2 macro-clusters within LNs was highly dependent on the site of skin sensitization. Differences between sites were driven by divergent activation states of migratory cDC2 from different dermal tissues, with enhanced costimulatory molecule expression by cDC2 in Th2-generating LNs promoting T cell macro-clustering and cytokine sensing. Thus, generation of dedicated priming micro-environments through enhanced costimulatory molecule signaling initiates the generation of Th2 responses in vivo and occurs in a skin site-specific manner.


Study of hydrodynamic behavior of a laboratory scale upflow anaerobic fixed film fixed bed reactor.
Application of anaerobic fixed film fixed bed reactor (AFFFB), containing mixed population of bacteria, helps in bacterial immobilization as biofilm on a support medium in the reactor overcoming the problem of biomass washout. Knowledge of hydrodynamics characteristics helps in better understanding and evaluating the performance of any reactor. This paper presents residence time distribution (RTD) studies carried out to investigate the hydrodynamic behavior of AFFFB reactor under the influence of varied hydraulic loading resulting in HRTs in range 24 hrs to 6 hrs. Results have demonstrated that the flow pattern is more close to a plug flow type and vary with varying intensity of dispersion and the extent of dispersion increases with decrease in HRTs.


DNA topoisomerase II as a potential factor in drug resistance of human malignancies.
The stabilization of the cleavable complex between DNA topoisomerase II and DNA by adriamycin (ADR), as well as by other topoisomerase II-targeted drugs, is an essential step in a process associated with drug cytotoxicity. Unlike many other cell types, ADR does not produce DNA cleavage in the lymphocytes of chronic lymphocytic leukemia (CLL). The CLL lymphocytes have been identified as quiescent cells with an extremely low level of topoisomerase II. The low level of this enzyme could constitute a basis for a new mechanism of drug resistance operating not only in CLL, but perhaps in any slow growing cancer with a large population of quiescent cells. Other factors contributing to drug resistance could include changes in enzyme regulation or processing of the cleavable complex, or the presence of a "mutant" enzyme which renders cancer cells unresponsive to topoisomerase II-targeted drugs. Suggested strategies in drug development, aimed at the topoisomerase II-related drug resistance, could include 1) the selection of topoisomerase I as an alternative target for cancer chemotherapy, 2) the development of ADR analogs which, unlike ADR, stabilize the topoisomerase II-DNA complex with high efficiency, and 3) the search for agents enhancing the SOS-like repair response, presumably triggered by DNA topoisomerase-targeted drugs.


[Research and development of an intelligent platform for respiratory therapy].
In recent years, the incidence of respiratory diseases has increased year on year. This has become a major global public health issue. To effectively treat respiratory diseases and improve the quality of life and prognosis of patients, the intelligent platform of respiratory therapy was established. Through real-time monitoring patients' important physiological indicators and integrating medical information, visual management, and intelligent decision making can be realized to provide personalized respiratory treatment and rehabilitation programs for critically ill patients. The platform can also provide reliable data support for medical research and further promote the development of the field of respiratory disease treatment. In the future, the platform will continue to improve the level and efficiency of clinical treatment, and truly solve practical problems for patients.


Inhibitor of transfer ribonucleic acid methylase in the differentiating slime mold Dictyostelium discoideum.
Eight hours after the onset of morphogenesis, an inhibitor of transfer ribonucleic acid methylases appears in differentiating Dictyostelium discoideum. The inhibitor is also present in spores. Fifty per cent of the inhibiting activity is lost upon heating at 100 C for 5 min; it is nondialyzable and sensitive to trypsin.


Pharmaceutical applications of graphene.
Nowadays, dynamic development in nanotechnological sciences is observed. Nanoparticles are frequently used in medicine and pharmacy as delivery systems for different kinds of active substances. One of the latest developed substances, with an unusually wide scope of utility, is graphene. The ways of its use in different fields of industry, not only pharmaceutical and medical, have been a subject of study for many research groups since the moment of its development in 2004. Graphene in pure form is highly hydrophobic. However, the presence of defects on its surface allows chemical modifications to be made, e.g. introduction of oxygen groups by covalent bonding. Also, non-covalent modifications are extensively used, including van der Waals forces, hydrogen bonding, coordination bonds, electrostatic and π-π stacking interactions. Due to the large surface area, graphene can be used in combination therapy, consisting in simultaneous administration of two or more pharmacologically active agents. Another interesting approach is gene therapy. Application of the PEI-graphene oxide system increased the efficacy of transfection. Possibilities of graphene and graphene oxide are not limited to their use as active substance delivery systems. These compounds by themselves were also found to be bacteriostatic and antibacterial agents.


Mutants of Arabidopsis thaliana with pleiotropic effects on the expression of the gene for beta-amylase and on the accumulation of anthocyanin that are inducible by sugars.
We identified a mutant of Arabidopsis thaliana ectotype Col-O in which significantly reduced levels of expression of the gene for beta-amylase (AT beta-Amy) were detected in leaves in response to high concentrations of sucrose, glucose or fructose. Genetic studies, including a cross with transgenic plants that harbored the AT beta-Amy:GUS transgene with the promoter of AT beta-Amy, indicated that this phenotype was caused by a recessive mutation, Iba1, that affected expression of AT beta-Amy in trans. We also found a reduced level of sugar-induced expression of AT beta-Amy in the Landsberg erecta (Ler) ecotype compared with other ecotypes. This phenotype seemed to be due to a recessive trait, provisionally designated Iba2, that was linked to neither erecta nor Iba1. The Iba2 mutation also affected expression of AT beta-Amy:GUS transgene. Accumulation of starch and sugars after treatment of leaves with sucrose was not affected in the Iba1 mutant and Ler plants. However, both Iba1 mutant and Ler plants accumulated low levels of anthocyanin in response to sucrose, results that suggested the existence of some genetic linkage between regulation of the expression of AT beta-Amy and regulation of the accumulation of anthocyanin. Although the Iba1 and Iba2 mutations did not affect sugar-inducible gene expression in general, the expression of sugar-regulated genes other than the gene for beta-amylase was differentially affected in the Iba1 mutant and Ler plants. These results suggest that the sugar-regulated expression of many genes in plants might be mediated by multiple signal-transduction pathways.


What Have We Learned from Design of Function in Large Proteins?
The overarching goal of computational protein design is to gain complete control over protein structure and function. The majority of sophisticated binders and enzymes, however, are large and exhibit diverse and complex folds that defy atomistic design calculations. Encouragingly, recent strategies that combine evolutionary constraints from natural homologs with atomistic calculations have significantly improved design accuracy. In these approaches, evolutionary constraints mitigate the risk from misfolding and aggregation, focusing atomistic design calculations on a small but highly enriched sequence subspace. Such methods have dramatically optimized diverse proteins, including vaccine immunogens, enzymes for sustainable chemistry, and proteins with therapeutic potential. The new generation of deep learning-based ab initio structure predictors can be combined with these methods to extend the scope of protein design, in principle, to any natural protein of known sequence. We envision that protein engineering will come to rely on completely computational methods to efficiently discover and optimize biomolecular activities.


Exploring relations between task conflict and informational conflict in the Stroop task.
In this study, we tested the proposal that the Stroop task involves two conflicts--task conflict and informational conflict. Task conflict was defined as the latency difference between color words and non-letter neutrals, and manipulated by varying the proportion of color words versus non-letter neutrals. Informational conflict was defined as the latency difference between incongruent and congruent trials and manipulated by varying the congruent-to-incongruent trial ratio. We replicated previous findings showing that increasing the ratio of incongruent-to-congruent trials reduces the latency difference between the incongruent and congruent condition (i.e., informational conflict), as does increasing the proportion of color words (i.e., task conflict). A significant under-additive interaction between the two proportion manipulations (congruent vs. incongruent and color words vs. neutrals) indicated that the effects of task conflict and informational conflict were not additive. By assessing task conflict as the contrast between color words and neutrals, we found that task conflict existed in all of our experimental conditions. Under specific conditions, when task conflict dominated behavior by explaining most of the variability between congruency conditions, we also found negative facilitation, thus demonstrating that this effect is a special case of task conflict.


Value of Clostridium difficile antigen test in immunocompromised hosts in the tropics.
39 fecal and body fluid specimens of immunocompromised patients who developed diarrhoea were tested for Clostridium difficile antigen test. The test was identified in only 11 and in one ascitic fluid. Endoscopy was performed in 5 patients and it showed pseudomembranous colitis in one. Numerous antibiotics were associated with C. difficile related diarrhea: ampicillin, 43%; cephalosporins, 43% and clindamycin, 14%. Three Salmonella sp., and one Entamoeba histolytica were detected among patients who later developed C. difficile associated diarrhea. The effect of oral vancomycin and fusidic acid was demonstrated in patients with C. difficile related diarrhea or colitis. The C. difficile antigen test is promising diagnostic tool in immunocompromised hosts in the tropics where both Salmonella and E. histolytica all are endemic.


Exactly solvable model of a slightly fluctuating ratchet.
We consider the motion of a Brownian particle in a sawtooth potential dichotomously modulated by a spatially harmonic perturbation. An explicit expression for the Laplace transform of the Green function of an extremely asymmetric sawtooth potential is obtained. With this result, within the approximation of small potential-energy fluctuations, the integration of the relations for the average particle velocity is performed in elementary terms. The obtained analytical result, its high-temperature, low-frequency, and high-frequency asymptotics, as well as numerical calculations performed for a sawtooth potential of an arbitrary symmetry, indicate that in such a system, the frequency-temperature controlling the magnitude and direction of the ratchet velocity becomes possible. We clarify the mechanism of the appearance of additional regions of nonmonotonicity in the frequency dependence of the average velocity, which leads to the appearance of additional ratchet stopping points. This mechanism is a consequence of the competition between the sliding time along the steep slope of the highly asymmetric sawtooth potential and the correlation time of the dichotomous noise.


Whole blood viscosity of preterm infants - differences to term neonates.
Determination of shear stresses at given shear rates with the LS 300 allows approximation of flow curves by mathematical models and to calculate viscosities of non-Newtonian fluids across the entire physiological shear range. Particular in preterm neonates, which in comparison to term neonates and adults have a substantially lower mean arterial blood pressure (MAP), rheological blood properties play a decisive role to maintain the perfusion. Whole blood viscosity was measured in umbilical cord blood taken from 34 preterm neonates using the LS 300 viscometer. In addition aggregation index, plasma viscosity, hematocrit and red blood cell (RBC) deformability was determined. The highest quality of approximation of the flow curve of whole blood was achieved by the method of Ostwald. Shear stresses of whole blood of preterm neonates were significantly lower compared to term neonates at similar shear rates (velocity range 6.16 s-1-50 s-1). With hematocrit calculated to 0.40 the related exponent (n) of the viscosity of preterm neonates (by Ostwald) showed a significant lower exponent (n) (0.71 ± 0.07) than term neonates (0.76 ± 0.06). The highest quality of approximation of the flow curve of plasma was achieved with the model of Ostwald in preterm neonates as well as in term neonates. The viscosity of plasma determined by Newton was lower for preterm neonates (0.89 ± 0.19) than for term neonates (1.04 ± 0.16). Concurrent to term neonates the whole blood of preterm neonates showed a very low aggregation index (term neonates 2.97 ± 2.10; preterm neonates 2.37 ± 1.32) and preterm neonates showed higher RBC deformability than term neonates. Because of the physiologically lower MAP and the particular viscous properties of neonatal blood special attention should be given when treating neonates with conventional blood products derived from adult donors.


Metabolic encephalopathy: neurologic and psychiatric considerations.
The diagnosis in patients who have psychiatric or neurologic manifestations as the result of toxins of great variety is not particularly difficult and usually can be achieved with a discerning history and physical examination. The EEG is a useful but not a necessary adjunct. The most difficult of these patients to sort out etiologically are those brought into the hospital, without history, in a flaccid coma or wild delirium or with mild or subtle delirium. The dementias are the main differential diagnosis. The hallmarks of metabolic encephalopathy are reduced awareness and fluctuating attention with defects in orientatioN, interpretation, memory, retention, and recall and with hesitant and clumsy motor performance. Prompt treatment is necessary to preserve the integrity of the master organ, the brain. Delay in treatment may convert metabolic encephalopathy into permanent dementia.


Annual vaccine-preventable disease report for New South Wales, Australia, 2014.
This report provides an epidemiological description of selected vaccine-preventable diseases in New South Wales (NSW), Australia, for 2014 to inform ongoing disease monitoring and control efforts. A trend of increasing pertussis notifications was observed, beginning midway through 2014 with the highest disease rates in the 5-9 year age group. Measles notifications increased to 67 cases in 2014 from 34 cases in 2013. Measles cases were associated with travel-related importations-predominantly from the Philippines-and secondary transmission increased compared to 2013 involving three main disease clusters. Notifications of invasive meningococcal disease continued to decline across the state with meningococcal B remaining the most common serogroup in NSW. Increasing rates of pertussis notifications from mid-2014 may indicate the beginning of an epidemic, ending the period of low transmission observed in 2013 and the first half of 2014. An increase in measles notifications in 2014, including secondary transmission, indicates the continued need for public health actions including robust follow-up and awareness campaigns.