Varieties of centralized intake: the Portland Target Cities Project experience.
To assess the possible influence of centralized intake on client outcomes, initial, six- and twelve-month Addiction Severity Index composite scores (in the alcohol, drug, legal and psychiatric areas) for clients who experienced provider intake were compared with scores for those going through two different models of centralized intake. Centralized intake clients were more likely than provider intake clients to have legal problems, and those legal problems became fewer over time. Clients from in-jail intake, including pretreatment services and accompanied placement, showed a greater initial and lower subsequent prevalence of drug, psychiatric and legal problems than the clients of the freestanding centralized intake. For all clients, psychiatric composite scores were powerful predictors of problems in alcohol, drug medical and legal areas, and psychiatric symptoms decreased over time. Since baseline differences in demographics and service assignment existed among the three groups, it was difficult to identify whether the outcome differences were due to the nature of the participants, the nature of the intake intervention, or both. However, the Portland Target Cities Projects's emphasis on in-jail centralized intake was associated with enhanced client outcomes.


Physical and computational analysis of the yeast Kluyveromyces lactis secreted proteome.
Secretion of proteins is the most common approach to protein expression in Kluyveromyces lactis. A proteomic analysis was performed on spent fermentation medium following bioreactor propagation of a wild-type industrial strain to identify proteins naturally secreted by K. lactis cells. Multidimensional separations were conducted and RP online ESI-MS/MS analysis identified 81 secreted proteins. In addition, an in silico analysis predicted 178 K. lactis proteins to be secreted via the general secretory pathway (GSP). These two datasets were compared and approximately 70% of the K. lactis proteins detected in the culture medium possessed a GSP sequence. The detected proteins included those involved with cell wall structure and synthesis, carbohydrate metabolism, and proteolysis, a result that may have significant bearing on heterologous protein expression. Additionally, both the experimental and in silico datasets were compared to similar, previously published datasets for Candida albicans. With the methodology presented here, we provide the deepest penetration into a yeast secretome yet reported.


A new record of the genus Froggattiella Leonardi (Hemiptera, Coccomorpha, Diaspididae) in South Korea.
The genus Froggattiella Leonardi, 1900 belongs to the family Diaspididae, and five species of Froggattiella have been recorded worldwide. In this study, Froggattiellapenicillata (Green, 1905), which attacks bamboos, is newly recorded in South Korea. The colonies of F.penicillata were collected on a bamboo forest located in Gajwa-dong, Jinju-si, Gyeongsangnam-do, South Korea (35.1599, 128.1029). Description of the adult female, host plant, adult female illustrations, and global distribution of this species are provided. Froggattiellapenicillata (Green, 1905) is reported for the first time in South Korea. This species occurrs under sheathing bases of the leaves and is observed attached on the stem and not on the leaf.


Engineering folate-drug conjugates to target cancer: from chemistry to clinic.
The folate receptor (FR) is a potentially useful biological target for the management of many human cancers. This membrane protein binds extracellular folates with very high affinity and, through an endocytic process, physically delivers them inside the cell for biological consumption. There are now many examples of how this physiological system can be exploited for the targeted delivery of biologically active molecules to cancer. In fact, strong preclinical as well as emerging clinical evidence exists showing how FR-positive cancers can be (i) anatomically identified using folate conjugates of radiodiagnostic imaging agents and (ii) effectively treated with companion folate-targeted chemotherapies. While the biological results are compelling, it is of equal importance to understand the conjugation chemistries that were developed to produce these active molecules. Therefore, this review will focus on the methods utilized to construct folate-based small-molecule drug conjugates (SMDCs), with particular attention focused on modular design, hydrophilic spacers, and self-immolative linkers.


NF-kappaB prevents TNF-alpha-induced apoptosis in an oligodendrocyte cell line.
Nuclear factor kappa beta (NF-kappaB) inhibits apoptosis in sensory, hippocampal, and striatal neurons of the central nervous system. Although several apoptotic stimuli have been shown to activate NF-kappaB in oligodendrocytes, the function of NF-kappaB in this cell type remains unknown. In this study, we introduced plasmids expressing either the p50- or p65-subunit of human NF-kappaB into Central Glia-4 (CG-4)--a rat oligodendrocyte precursor cell line-and determined the influence of NF-kappaB function on tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis. Expression of NF-kappaB markedly prevented CG-4 apoptosis, with p50 being more effective than p65. This anti-apoptotic activity was repressed by IkappaB-alpha, an inhibitor of NF-kappaB. These results imply that NF-kappaB acts as a potent inhibitor of TNF-induced apoptosis in oligodendrocytes.


Drug distribution and binding to muscle in rat.
Drug binding to rat skeletal muscle homogenate was studied using quinidine and quinine as basic drugs, and furosemide and phenylbutazone as anionic drugs. Characteristically different binding fashions were observed among basic and anionic drugs. Quinidine and quinine which are stereoisomers bound to muscle not depending on drug concentration and showed similar binding ratios, while furosemide and phenylbutazone bound to muscle depending on drug concentration. Quinidine and quinine bound mainly to 1000 x g precipitates of muscle homogenate while furosemide and phenylbutazone bound exclusively to cytosol fraction. Binding to 1000 x g precipitates was not explained by binding to actin and myosin alone, while the second protein fraction eluted from cytosol by Sephadex G-75 gel filtration was found to have binding properties for furosemide.


The hypernoradrenergic state in vasodilator drug-treated hypertensive patients: effect of clonidine.
We studied 11 previously refractory hypertensive subjects who were treated with minoxidil, propranolol, and diuretics for 2--7 years. During this time 70 random blood samples were collected in the supine position and analyzed for plasma norepinephrine (PNE) and plasma renin activity (PRA). The mean PNE was 546 pg/ml (normal mean +/- SE, 173 +/- 10) and was reciprocally related to log PRA. To determine if this elevated PNE would respond to clonidine, 5 of the patients were admitted to the General Clinical Research Center for administration of placebo and later of clonidine (0.1 or 0.2 mg). A single dose of clonidine suppressed PNE (p less than 0.01) and lowered mean blood pressure (p less than 0.02) for 12 hr. The PRA was not altered significantly by clonidine. Thus, high PNE in these treated patients can be suppressed by clonidine, and this suppression of PNE and blood pressure occurs without alteration of PRA.


"Chickens Are a Lot Smarter than I Originally Thought": Changes in Student Attitudes to Chickens Following a Chicken Training Class.
A practical class using clicker training of chickens to apply knowledge of how animals learn and practice skills in animal training was added to an undergraduate course. Since attitudes to animals are related to their perceived intelligence, surveys of student attitudes were completed pre- and post- the practical class, to determine if (1) the practical class changed students' attitudes to chickens and their ability to experience affective states, and (2) any changes were related to previous contact with chickens, training experience or gender. In the post- versus pre-surveys, students agreed more that chickens are easy to teach tricks to, are intelligent, and have individual personalities and disagreed more that they are difficult to train and are slow learners. Following the class, they were more likely to believe chickens experience boredom, frustration and happiness. Females rated the intelligence and ability to experience affective states in chickens more highly than males, although there were shifts in attitude in both genders. This study demonstrated shifts in attitudes following a practical class teaching clicker training in chickens. Similar practical classes may provide an effective method of teaching animal training skills and promoting more positive attitudes to animals.


Prevalence, Management, and Long-Term (6-Year) Outcomes of Atrial Fibrillation Among Patients Receiving Drug-Eluting Coronary Stents.
This study sought to investigate the incidence, management, and clinical relevance of atrial fibrillation (AF) during and after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and evaluate outcomes of different antithrombotic strategies. Uncertainty exists regarding the optimal antithrombotic strategy in patients with AF who are undergoing PCI with DES. Using a consecutive series of 10,027 patients who underwent DES implantation between 2003 and 2011, we evaluated the overall prevalence and clinical impact of AF. In addition, we compared the efficacy and safety of dual antiplatelet therapy (DAPT) (aspirin plus clopidogrel) and triple therapy (DAPT plus warfarin) among patients with AF. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke. Overall, 711 (7.1%) patients had a diagnosis of AF at the index PCI. Patients with AF were older, had more comorbid conditions, and more often had a history of strokes; most patients with AF (88.4%) received DAPT rather than triple therapy (10.5%) at discharge. The rate of primary outcome after PCI during the 6-year follow-up period was significantly higher in patients with AF than in those without AF (22.1% vs. 8.0%; p < 0.001). This trend was consistent for major bleeding (4.5% vs. 1.5%; p < 0.001). After multivariable adjustment, the presence of AF was significantly associated with a higher risk of primary outcome (hazard ratio [HR]: 2.33; 95% confidence interval [CI]: 1.95 to 2.79; p < 0.001) and major bleeding (HR: 2.01; 95% CI: 1.32 to 3.06; p = 0.001). Among patients with AF, adjusted risk for the primary outcome was similar between the DAPT group and the triple therapy group (HR: 1.01; 95% CI: 0.60 to 1.69; p = 0.98), but triple therapy was associated with a significantly higher risk of hemorrhagic stroke (HR: 7.73; 95% CI: 2.14 to 27.91; p = 0.002) and major bleeding (HR: 4.48; 95% CI: 1.81 to 11.08; p = 0.001). Among patients receiving DES implantation, AF was not rare and was associated with increased ischemic and bleeding risk. In patients with AF, triple therapy was not associated with decreased ischemic events but was associated with increased bleeding risk compared to DAPT.


Fasting serum sulfate levels before and after development of osteoarthritis in participants of the veterans administration normative aging longitudinal study do not differ from levels in participants in whom osteoarthritis did not develop.
To determine whether the development of osteoarthritis (OA) in men over a 33-year period is related to lower sulfate levels in stored serum collected during that time interval. Stored serum samples from participants in the Veterans Administration Normative Aging Study were assayed for sulfate by ion-exchange chromatography. Samples had been obtained every 3-5 years during part or all of a 33-year portion of the study. Sulfate levels were determined in serum from all participants who underwent knee replacement surgery and had evidence of radiographic hand OA, from some of the participants who had evidence of radiographic hand OA but had not undergone knee replacement surgery, from all participants who underwent knee replacement surgery but had no evidence of radiographic hand OA, and from age-matched participants who had no evidence of OA by history, physical examination, or hand radiography. Serum sulfate levels in participants, with or without radiographic hand OA and/or knee replacements, who were ages 34-72 years at the first examination, ranged from 0.21 mM to 0.51 mM over the course of a maximum of 33 years. Both the overall mean and median sulfate levels rose from 0.32 mM at age 40-50 years to 0.38 mM at age 70-80 years, and the overall mean and median for all ages was 0.36 mM. There were no significant differences in sulfate levels between subjects in any of the 4 groups. There was no evidence of a relationship between these serum sulfate levels and the development of OA. However, all samples were collected after overnight fasting, and no participant was younger than age 34 years at the initiation of the study. It remains to be determined whether differences in the time of ingestion of daily dietary protein providing sulfate are related to the development of OA, or whether sulfate levels measured at an earlier age could be a factor.


Fast determination of retinol and alpha-tocopherol in plasma by LC.
A fast, selective and economical method for the determination of retinol and alpha-tocopherol is presented. Both vitamins are separated by high-performance liquid chromatography (HPLC) in less than 4 min using an isocratic elution with methanol. The robustness of the method was checked in real samples, obtaining relative standard deviation lower than 3%. The described method was satisfactorily applied to serum samples proceeding of patients enrolled in a METHADONE maintenance treatment program. The retinol concentrations in the serum of these patients fell into the normal interval of concentrations; however, the serum alpha-tocopherol contents were higher than the normal values.


Changes in sunburn and tanning attitudes among lifeguards over a summer season.
Skin cancer is one of the most common cancers in the United States. Lifeguards are at increased risk of excessive sun exposure and sunburn. We sought to examine changes in: (1) sunburn frequency over a summer while controlling for sun exposure, sun protection habits, and participation in a skin cancer prevention program; and (2) tanning attitudes while controlling for participation in the program. Participants in this study were lifeguards (n = 3014) at swimming pools participating in the Pool Cool program in 2005. Lifeguards completed surveys at the beginning and end of the summer. Sequential regression analyses were used to assess changes in sunburn frequency and tanning attitudes. Sunburn frequency decreased between baseline and follow-up. Having a sunburn over the summer was significantly predicted by baseline sunburn history, ethnicity, skin cancer risk, and sun exposure. The tanning attitude, "People are more attractive if they have a tan," was significantly predicted from baseline tanning attitude and ethnicity. The second tanning attitude, "It helps to have a good base suntan," was significantly predicted by baseline tanning attitude, ethnicity, basic/enhanced group, and moderate skin cancer risk. Self-reported data and limited generalizability to lifeguards at other outdoor pools are limitations. The findings showed that previous sunburn history is an important predictor of sunburn prospectively. In addition, a more risky tanning attitude is an important predictor of future attitudes toward tanning. Active involvement in targeted prevention programs may help to increase preventive behavior and health risk reduction.


Methylprednisolone versus triamcinolone in painful shoulder using ultrasound-guided injection.
There is little evidence about the comparative efficacy of corticosteroids in the treatment of painful shoulder. The main aim was to compare the efficacy of methylprednisolone (MTP) versus triamcinolone (TMC) in the treatment of painful shoulder using an ultrasound-guided injection. Patients with painful shoulder due to subacromial bursitis and partial or full-thickness rotator cuff tears demonstrated by musculoskeletal ultrasound received a guided-injection of MTP acetate 40 mg (12 patients) or TMC acetonide 40 mg (12 patients). Range of motion and pain visual analogue scale were registered at 10 and 30 min, 1 and 2 weeks postinjection. Two weeks postinjection, both groups reported a mean improvement in range of motion (33%) and relief of pain (61%). Relief of pain of 50% or more was observed in 92% of patients in MTP group and 50% of TMC group (p = 0.02). Two months postinjection, 50% of the patients in MTP group and 25% in TMC group reported total relief of pain (p = 0.3). Patients with painful shoulder receiving an ultrasound-guided injection of MTP or TMC have a rapid and sustained overall response. Relief of pain tends to be more rapid with MTP than TMC.


Hartmann's procedure in rectal cancer: a population-based study of postoperative complications.
Hartmann's procedure for rectal cancer patients is increasingly performed but few studies have reported the postoperative outcome. The purpose was to report postoperative complications and analyse risk factors in rectal cancer patients operated with Hartmann's procedure. To describe the selection and postoperative complication patterns, all bowel-resected rectal cancer patients were included. Population-based data were from the county of Västmanland, Sweden. All rectal cancer patients operated with an elective bowel resection between 1996 and 2012 were included. Demographics and postoperative complications were prospectively registered and data retrospectively analysed. Of the 624 patients included, 396 (64%) were operated with an anterior resection, 159 (25%) with an abdominoperineal excision and 69 (11%) a Hartmann's procedure of which 90% were low Hartmann's. Patients operated with a Hartmann's procedure were significantly older, had higher ASA-score, poorer WHO performance score and lower serum albumin levels. Operative time for Hartmann's procedure was a median of 49 and 99 min shorter than after anterior resection and abdominoperineal excision, respectively, and entailed less bleeding. Complications related to the pelvic and perineal dissections were more common after abdominoperineal excision compared with anterior resection and Hartmann's procedure (32 vs. 9 and 13%, p < 0.001). Few rectal cancer patients, operated with Hartmann's procedure, developed pelvic complications despite a higher age, more co-morbidities, metastases in different localities and functional inferiority when compared with the patients operated with anterior resection or abdominoperineal excision. Hartmann's procedure is a valid alternative procedure in the old and frail rectal cancer patient.


The common marmoset (Callithrix jacchus) has two very similar semenogelin genes as the result of gene conversion.
The semen coagulum proteins have undergone substantial structural changes during evolution. In primates, these seminal vesicle-secreted proteins are known as semenogelin I (SEMG1) and semenogelin II (SEMG2). Previous studies on the common marmoset (Callithrix jacchus) showed that ejaculated semen from this New World monkey contains semenogelin, but it remained unclear whether it carries both genes or only SEMG1 and no SEMG2, like the closely related cotton-top tamarin (Saguinus oedipus). In this study we show that there are two genes, both expressed in the seminal vesicles. Surprisingly, the genes show an almost perfect sequence identity in a region of 1.25 kb, encompassing nearly half of the genes and containing exon 1, intron 1, and the first 0.9 kb of exon 2. The underlying molecular mechanism is most likely gene conversion, and a phylogenetic analysis suggests that SEMG1 is the most probable donor gene. The marmoset SEMG1 in this report differs from a previously reported cDNA by a lack of nucleotides encoding one repeat of 60 amino acids, suggesting that marmoset SEMG1 displays allelic size variation. This is similar to what was recently demonstrated in humans, but in marmosets the polymorphism was generated by a repeat duplication, whereas in humans it was a deletion. Together, these studies shed new light on the evolution of semenogelins and the mechanisms that have generated the structural diversity of semen coagulum proteins.


"Three-in-One" Nanozyme Composite for Augmented Cascade Catalytic Tumor Therapy.
Cascade catalytic reaction exhibits simple procedure and high efficiency, such as that from the orderly assembly of different enzymes in biological systems. Mimicking of the natural cascade procedure becomes critical, but the orderly assembly of different enzymes is still challenging. Herein, single Au-Pt nanozyme is reported with "three-in-one" functions to initiate cascade conversions for O2 supply as mimic catalase, H2 O2 production with its glucose oxidase-like property, and • OH generation as mimic peroxidase for chemodynamic therapy (CDT). Thus, the complex assembly and cross-talk among the different enzymes are avoided. To this end, metastable Cu2 O NPs, as scaffolds, are used to anchor ultrasmall Au-Pt nanozyme, while metal-organic framework (MOF) is used to encapsulate the nanozyme for tumor microenvironment response and shielding protein adsorption. Pluronic F127 is then modified on the surface to improve hydrophilicity and biocompatibility of the composite. The endogenous acidity and glutathione in tumor degrade MOF to expose nanozyme for cascade catalytic CDT. The high photothermal conversion ability also enhances the CDT, while Cu2+ ions consume GSH to further improve CDT efficiency as augmented cascade catalytic tumor therapy. Thus, a new paradigm is provided with drug-free single nanozyme for improving tumor therapeutic efficacy and minimizing side effects.


Firearm suicide decedents in the Republic of Ireland, 1980-2005.
To compare the sociodemographic characteristics of firearms suicide decedents and other suicide decedents in the Republic of Ireland between 1980 and 2005. A cross-sectional study of sociodemographic characteristics of those who committed suicide with a firearm and those who committed suicide by an alternative method. Suicide data from 1980 to 2005 inclusive, provided by the Central Statistics Office of Ireland, were analysed. For the purpose of this paper, suicide method was collapsed into two groups: firearm-assisted suicide (FAS) and non-firearm-assisted suicide (n-FAS). Differences in gender, marital status (married vs not married), area of residence (urban vs rural), agri-employment (agri-employed vs not agri-employed) and age were examined between the two groups. A logistic regression is presented using suicide method (FAS vs n-FAS) as the criterion variable and individual factors as predictors. In total, 9674 suicides were recorded from 1 January 1980 to 31 December 2005. Seven hundred and ninety-three of these were FAS and 8881 were n-FAS. For both suicide profiles, the deceased were predominantly male, living in a rural setting and not married. However, this profile was more salient in the FAS group. In comparison with the n-FAS group, a greater proportion of the FAS decedents were male [chi(2)(1)=152.5, P< or =0.0001, odds ratio (OR)=4.5, 95% confidence interval (CI) 3.4-6.1], from a rural setting [chi(2)(1)=153.5, P< or =0.0001, OR=4.4, 95%CI 3.2-5.6) and agri-employed [chi(2)(1)=21.3, P< or =0.0001, OR=1.5, 95%CI 1.3-1.8). FAS decedents were significantly younger than n-FAS victims, although the size of this effect was small (z=-8.4, P<0.0005, r=-0.1). There was no difference in marital status between the two groups. Risk factors for FAS should inform policy-making in this area, with particular attention paid to protecting young males resident in rural settings. Consideration should be given to targeting agri-employed individuals as a specific at-risk group.


Development of a Measles and Rubella Multiplex Bead Serological Assay for Assessing Population Immunity.
Serosurveys are important tools for estimating population immunity and providing immunization activity guidance. The measles and rubella multiplex bead assay (MBA) offers multiple advantages over standard serological assays and was validated by comparison with the enzyme-linked immunosorbent assay (ELISA) and the measles plaque reduction neutralization (PRN) assay. Results from a laboratory-produced purified measles virus whole-virus antigen MBA (MeV WVAL) correlated better with ELISA and PRN than results from the baculovirus-expressed measles nucleoprotein (N) MBA. Therefore, a commercially produced whole-virus antigen (MeV WVAC) was evaluated. Serum IgG antibody concentrations correlated significantly with a strong linear relationship between the MeV WVAC and MeV WVAL MBAs (R = 0.962 and R2 = 0.926). IgG concentrations from the MeV WVAC MBA showed strong correlation with PRN titers (R = 0.846), with a linear relationship comparable to values obtained with the MeV WVAL MBA and PRN assay (R2 = 0.716 and R2 = 0.768, respectively). Receiver operating characteristic (ROC) curve analysis of the MeV WVAC using PRN titer as the comparator resulted in a seroprotection cutoff of 153 mIU/ml, similar to the established correlate of protection of 120 mIU/ml, with a sensitivity of 98% and a specificity of 83%. IgG concentrations correlated strongly between the rubella WVA MBA and ELISA (R = 0.959 and R2 = 0.919). ROC analysis of the rubella MBA using ELISA as the comparator yielded a cutoff of 9.36 IU/ml, similar to the accepted cutoff of 10 IU/ml for seroprotection, with a sensitivity of 99% and a specificity of 100%. These results support use of the MBA for multiantigen serosurveys assessing measles and rubella population immunity.


The effect of macrophage development on the release of reactive oxygen intermediates and lipid oxidation products, and their ability to induce oxidative DNA damage in mammalian cells.
Inflammation and the release of potentially damaging substances, such as reactive oxygen intermediates (ROI) and lipid oxidation products from inflammatory cells, have been linked to the potentiation of carcinogenesis. Murine macrophages when stimulated with phorbol esters induce 5,6 ring saturated thymine residues (T'), a lesion of known oxidative origin, in co-cultivated mammalian cells. Induction of this damage was inhibited by catalase and induced in target cells by reagent H2O2 alone. In the present studies, we used defined populations of macrophages with high, low and intermediate capacities for the release of H2O2 or metabolites of arachidonic acid (AA) to assess the relative contribution of these classes of compounds to the induction of saturated thymines. Macrophages activated with Bacillus Calmette-Guerin (BCG), which have the highest capacity for the release of H2O2 and the lowest for the release of metabolites of AA, induced the lowest levels of saturated thymines. Resident macrophages from the unmanipulated peritoneum, which have the lowest capacity for the production of H2O2 and the highest capacity for release of AA metabolites, induced more saturated thymines than did the BCG macrophages. Inflammatory macrophages elicited by casein, which have an intermediate capacity for release of H2O2 and AA metabolites, induced the highest level of saturated thymines. Zymosan, which induced more release of AA metabolites than release of H2O2, was a better stimulant for the induction of T' than TPA, which is a better stimulant for secretion of H2O2. Nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase and cyclooxygenase pathways for metabolism of AA, inhibited the induction of T' by resident macrophages. Indomethacin, an inhibitor of the cyclo-oxygenase path, enhanced induction of T'. Taken together, the data suggest that while H2O2 has the capacity to induce T' in 3T3 cells, it may not be the only mediator of DNA damage and that lipoxygenase generated metabolites of AA may (alone or in concert with ROI) play an important role in the induction of oxidative DNA damage by macrophages.


[Analysis of occurrence of Chlamydophila pneumoniae infection serological markers in patients with bronchial asthma].
Numerous publications pointing the role of Chlamydophila pneumoniae infections in etiopathogenesis of bronchial asthma have appeared in recent years. Up to the presence the diagnostics of Chlamydophila pneumoniae infections has been based on the serological examinations especially on indirect microimmunofluorescence which is regarded to be a "gold standard". The aim of the paper was to compare the occurrence of Chlamydophila pneumoniae infection serological markers in the group of patients with asthma (N = 38) and in the control group (N = 38). The obtained results have allowed making the following conclusions: 1. The increased level of IgG class anti-Chlamydophila pneumoniae antibodies in the group of patients with asthma, which proves more frequent contact with Chlamydophila pneumoniae in that group, seems to support the hypothesis about the role of chlamydial infections in etiopathogenesis of bronchial asthma. 2. The single assessment of anti-Chlamydophila pneumoniae antibodies in the ELISA test has not allowed determining the type of chlamydial infection in unambiguous way. However, with reference to the entire clinical picture, the statement of the contact with Chlamydophila pneumoniae can be helpful especially in the treatment of severe asthma.


Relationship between immune parameters and organ involvement in children with Henoch-Schonlein purpura.
Henoch-Schonlein purpura (HSP) is the most common type of connective tissue diseases which increasingly occurs in children in recent years and its pathogenesis remains unclear. In order to explore the immune parameters and underlying pathogenesis mechanism of children with HSP, the study involved 1232 patients with HSP having different clinical symptoms and their laboratory indicators were evaluated. Th1/Th2 imbalance and overactivity of Th2 cells can cause increase in the synthesis and release of immunoglobulins in children with HSP. The number of red blood cells and white blood cells in urine was directly proportional to the level of IgA and inversely proportional to the level of serum complements (C3 and C4). Activation of these complements caused by immunoglobulin in patients with HSP plays an important role in renal injury. The urinary protein content in children with HSP along with proteinuria was positively correlated with IgE level, and IgE mediated type 1 hypersensitivity can cause increase in capillary permeability and weakened the charge barrier; hence, it could be considered as one of the causes of proteinuria in HSP. Additionally, the NK cells percentage was reduced and impaired immune function of NK cells were related to the immune injury of the digestive tract and kidney.


Radiotoxicity of 125I-iododeoxyuridine in pre-implantation mouse embryos.
The radiotoxicity of DNA incorporated 125I in cultured pre-implantation two-cell mouse embryos was investigated and compared with external gamma-irradiation. The uptake of 125IdU in the two-cell stage embryos was determined as a function of incubation time and concentration of radioactivity (MBq/ml) in the medium. The absorbed dose to the embryos was calculated using conventional procedures. The embryo survival curves show that the dose at 37% survival is only about 15 cGy for 125IdU, whereas for 137Cs-photons it is 175 cGy. The extreme toxicity observed is thought to be due to the localized energy deposition of the numerous low energy Auger electrons emitted in the decay of 125I. These results are consistent with earlier observations in mouse testis and cultured cells and point to the need for assessing the radiation risk from incorporated Auger electron emitting radionuclides based on their subcellular distribution.


Hospitalization of Patients With Diabetes Due to Ketoacidosis Before and After the Initiation of Sodium-Glucose Cotransporter-2 Inhibitors.
Diabetic ketoacidosis (DKA) is a rare side effect related to sodium-glucose cotransporter-2 inhibitors (SGLT2I). This study investigated the incidence of people with diabetes hospitalized because of DKA after the implementation of SGLT2I (2015-2019), compared with the pre-SGLT2I era. In this retrospective cohort study, medical records of all adult patients hospitalized with a diagnosis of DKA in a tertiary referral center from 2011-2019 were reviewed. The incidence of DKA was compared between the periods 2011-2014 and 2015-2019. Demographic and clinical data of patients hospitalized with DKA as well as SGLT2I use were extracted. During 2011-2019, there were 186 hospitalizations because of DKA. The rate of hospitalization was stable during 2011-2019 at 0.22% ± 0.04% (95% CI, 0.18-0.25). The clinical characteristics of people hospitalized with DKA in 2011-2014 were similar to those of people hospitalized during 2015-2019. Only 7 people (6.1%) in the 2015-2019 cohort had SGLT2I-related DKA, and their clinical characteristics were similar to those of the rest of the cohort. The rate of hospitalizations because of DKA remained stable before and 5 years after SGLT2I were implemented for the treatment of type 2 diabetes mellitus. Larger, multi-institutional studies with longer follow-ups are needed to study the effect of SGLT2I on the rate of hospitalizations because of DKA among people with diabetes. Although DKA events associated with SGLT2I are rare, they should be strongly considered in the differential diagnosis of people treated with these medications.


LRRK2 kinase activity mediates toxic interactions between genetic mutation and oxidative stress in a Drosophila model: suppression by curcumin.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by selective loss of dopaminergic neurons and the presence of Lewy bodies. The pathogenesis of PD is believed to involve both genetic susceptibility and environmental factors. Mutations in Leucine-rich repeat kinase 2 (LRRK2) cause genetic forms of PD, and the LRRK2 locus contributes to sporadic PD. Environmental toxins are believed to act in part by causing oxidative stress. Here we employed cell and Drosophila models to investigate the interaction between LRRK2 genetic mutations and oxidative stress. We found that H(2)O(2) increased LRRK2 kinase activity and enhanced LRRK2 cell toxicity in cultured cells and mouse primary cortical neurons. Furthermore, a sub-toxic dose of H(2)O(2) significantly shortened the survival of LRRK2 transgenic flies and augmented LRRK2-induced locomotor defects and dopamine neuron loss. Treatment with a LRRK2 kinase inhibitor (GW5074) or an anti-oxidant (curcumin) significantly suppressed these PD-like phenotypes in flies. Moreover, curcumin significantly reduced LRRK2 kinase activity and the levels of oxidized proteins, and thus acted as not only an antioxidant but also a LRRK2 kinase inhibitor. These results indicate that LRRK2 genetic alterations can interact with oxidative stress, converging on a pathogenic pathway that may be related to PD. These studies also identified curcumin as a LRRK2 kinase inhibitor that may be a useful candidate for LRRK2-linked PD intervention.


Epigenetic marks in suicide: a review.
Suicide is a complex phenomenon and a global public health problem that involves several biological factors that could contribute to the pathophysiology of suicide. There is evidence that epigenetic factors influence some psychiatric disorders, suggesting a predisposition to suicide or suicidal behavior. Here, we review studies of molecular mechanisms of suicide in an epigenetic perspective in the postmortem brain of suicide completers and peripheral blood cells of suicide attempters. Besides, we include studies of gene-specific DNA methylation, epigenome-wide association, histone modification, and interfering RNAs as epigenetic factors. This review provides an overview of the epigenetic mechanisms described in different biological systems related to suicide, contributing to an understanding of the genetic regulation in suicide. We conclude that epigenetic marks are potential biomarkers in suicide, and they could become attractive therapeutic targets due to their reversibility and importance in regulating gene expression.


[Progress in sleep-disordered breathing in idiopathic pulmonary fibrosis].
Idiopathic pulmonary fibrosis (IPF) is one of the most common idiopathic interstitial pneumonia. The main symptoms for IPF are dry cough and exertional shortness of breath, which is worsen gradually with the development of pulmonary fibrosis. Patients with IPF often suffer from sleep disordered breathing (SDB). Sleep architecture for these patients including the sleep efficiency, deep sleep, rapid eye movement sleep and arousal index, are changed, which seriously affects the quality of life. In the absence of effective therapies, optimizing the quality of life may become a major therapeutic target for IPF. The diagnosis and treatment of SDB can significantly improve the quality of life for patients with IPF.


Clinical Relevance of the High Prevalence of MYD88 L265P Mutated Vitreoretinal Lymphoma Identified by Droplet Digital Polymerase Chain Reaction.
Purpose: To investigate the frequency and clinical relevance of missense mutation at position 265 changing leucine to proline in the myeloid differentiation factor 88 gene (MYD88 L265P) in the vitreous of Chinese patients with vitreoretinal lymphoma (VRL) using droplet digital polymerase chain reaction (ddPCR).Methods: Vitreous fluid (VF) from 29 eyes of 20 VRL patients at the North Huashan Hospital were included. MYD88 L265P analysis of VF was performed using ddPCR. Associations between clinicopathologic characteristics and MYD88 mutation were analyzed using t-test or Fisher's exact test.Results: MYD88 L265P mutations were detected in 22 of 29 samples from 14 patients with diffuse large B-cell lymphomas and one patient with lymphoplasmacytoid lymphoma. However, no significant associations were found between MYD88 L265P mutation status and age, sex, lymphoma subtype or location of the primary lesion.Conclusion: The high prevalence of MYD88 L265P identified by ddPCR suggests that this method of evaluating the frequency of MYD88 L265P is a promising tool for accurate diagnosis of VRL.


Secondary amenorrhoea and oral contraceptives.
Eight-seven cases of secondary amenorrhoea of more than 6 months' duration developing after treatment with oral contraceptives (group I) were compared with 227 cases of secondary amenorrhoea not preceded by treatment with combined tablets (group II). The two groups were collected during the same period. The average age of the patients was 4 years higher in group I than in group II. Oligomenorrhoea and previously occurred in 30% of group I and in 46% of group II. Pronounced predisposing factors., such as psychogenic trauma and stress with or without considerable change in body weight, were encountered in 26% in group I and 56% in group II. The incidence of increased urinary output of 17-keto steroids, 17-ketogenic steroids and of hirsutism was slightly higher in group II. The percentage of eosinophilic cells in vaginal scrapings was low in 20% in group I as compared with 46% in group II. Spontaneous return of pituitary-ovarian function occurred in 40% in both groups. Patients recovering spontaneously in group I presented a maximum during the first few months, followed by a steady and fairly uniform decline. Spontaneous recovery in group II was more or less independent of time. It seems reasonable to believe that oral contraceptives did promote or contribute to the development of secondary amenorrhoea in about 50%, representing cases with various predisposing factors. A causal relation between oral contraceptives and secondary amenorrhoea was indicated in the remaining 50% because of perfectly normal ovarian function before treatment and absence of predisposing factors.


Facile minimally invasive cardiac surgery via ministernotomy.
The public's and surgeons' perception of minimally invasive operations are frequently at odds. Nevertheless, real or perceived benefits may result from limiting skin and skeletal trauma. Beginning in January 1996, we began approaching most infant and pediatric open heart procedures through an upper sternal split incision using a 1- to 3-inch skin opening and then extended this technique using a 2.5- to 3.5-inch incision for adult aortic and mitral valve replacement. A total of 82 patients, 57 infants and children and 25 adults, have been operated on using this approach (age range, newborn to 81 years). Operations accomplished through ministernotomy have included aortic valvotomy, arterial switch, tetralogy of Fallot, atrial or ventricular septal defect closure, aortic valve replacement, mitral valve replacement and repair, redo aortic or mitral valve replacement, double valve replacement, aortic root replacement, and complex arch reconstruction. In adults, the sternum was divided and then a T incision was made at the second, third, or fourth intercostal space. The mitral valve was reached through the roof of the left atrium. In children, a lower sternal split was used for atrial septal defect repairs. All cannulas were introduced through the ministernotomy incision, eliminating femoral cannulation. No new instruments, retractors, or ports were used. Mediastinal drainage was accomplished through a Blake drain connected to Heimlich-valved grenade suction. All but 2 patients were extubated immediately. Hospital stay was from 1 to 20 days (median 2 days). Patient and family acceptance is very high. On the basis of this initial experience, we attempt all congenital cardiac and isolated adult valve operations through ministernotomy.


GSTT1 and GSTM1 deletions, NQO1 C609T polymorphism and risk of chronic myelogenous leukemia in Japanese.
We conducted a prevalent case-control study with 51 chronic myelogenous leukemia (CML) cases and 476 controls to investigate the associations between glutathione S-transferase T1 (GSTT1), glutathione S-transferase M1 (GSTM1) deletions, and the NAD(P)H:quinone oxidoreductase 1 (NQO1) C609T polymorphism with risk of chronic myelocytic leukemia in Japanese. For the GSTT1 deletion, when the GSTT1 positive genotype was defined as the reference, the OR for the GSTT1 deletion genotype was 1.32 (95%CI; 0.74-2.36). For the GSTM1 deletion, when the GSTM1 positive genotype was defined as the reference, the OR for the GSTM1 deletion genotype was 0.95 (95%CI; 0.53-1.69). For NQO1 C609T polymorphism, when the NQO1 609CC genotype was defined as the reference, the ORs for the CT genotype, TT genotype, and CT and TT genotypes combined together were 2.37 (95%CI, 1.21-4.67, P=0.012), 1.44 (0.55-3.74, P=0.012) and 2.12 (1.10-4.08, P=0.025), respectively. The present study revealed that the risk of CML was modulated little by GSTT1 and GSTM1 deletions, but a statistically significant association between NQO1 C609T polymorphism and CML was observed for Japanese. Incidence case-control studies with a larger statistical power are now required to confirm our findings.


[Letournel ilioinguinal approach in the management of acetabular fractures].
The ilioinguinal approach described by Emile Letournel in 1961 allows an extensive exposure of the anterior elements of the pelvis and acetabular fractures involving the anterior wall and/or column, pubic symphysis, and sacroiliac joint. It also facilitates a rapid recovery of muscle function and leaves a cosmetic scar.


Piebaldism.
Piebaldism is an uncommon autosomal dominantly inherited pigment anomaly characterized by a congenital white forelock and leukoderma on the frontal scalp, forehead, ventral trunk and extremities. It is caused by a loss-of-function mutation in the KIT gene. Genetic analyses reveal a consistent genotype-phenotype relationship in piebaldism. However, recently reported cases of piebaldism that are milder or severer than genetically expected indicate that other factors, such as a modifier gene of MC1R, influence skin and hair color. The KIT ligand/KIT that triggers the Ras/mitogen-activated protein kinase signaling pathway play essential functions in the migration, proliferation, survival, melanogenesis and melanosome transfer of the melanocytes. We summarize current research progress in piebaldism and related disorders.


The proapoptotic tumor suppressor protein kinase C-delta is lost in human squamous cell carcinomas.
Protein kinase C (PKC)-delta is proapoptotic in human keratinocytes, and is downregulated or inactivated in keratinocytes expressing the activated Ha-ras oncogene, making it a candidate tumor suppressor gene for squamous cell carcinoma (SCC). We evaluated the significance of PKC-delta loss in transformed human keratinocytes using tumorigenic HaCaT Ras II-4 cells that have significantly reduced PKC-delta levels. Re-expression of PKC-delta by retrovirus transduction caused an increase in apoptosis and growth inhibition in culture. The growth inhibition induced by PKC-delta could be partially reversed by Bcl-x(L) expression, indicating that apoptosis was in part responsible for PKC-delta-induced growth inhibition. PKC-delta re-expression suppressed the tumorigenicity of HaCaT Ras II-4 cells in nude mice (P<0.05), and the small tumors that did form contained elevated levels of activated caspase-3, indicating increased apoptosis. In addition, we found that 29% (12/42) of human Bowen's disease (squamous carcinoma in situ) or SCC cases had absent or reduced PKC-delta when compared to the surrounding normal epidermis. These results indicate that PKC-delta inhibits transformed keratinocyte growth by inducing apoptosis, and that PKC-delta may function as a tumor suppressor in human SCCs where its loss in cells harboring activated ras could provide a growth advantage by conferring resistance to apoptosis.


Move faster, think later: Women who play action video games have quicker visually-guided responses with later onset visuomotor-related brain activity.
A history of action video game (AVG) playing is associated with improvements in several visuospatial and attention-related skills and these improvements may be transferable to unrelated tasks. These facts make video games a potential medium for skill-training and rehabilitation. However, examinations of the neural correlates underlying these observations are almost non-existent in the visuomotor system. Further, the vast majority of studies on the effects of a history of AVG play have been done using almost exclusively male participants. Therefore, to begin to fill these gaps in the literature, we present findings from two experiments. In the first, we use functional MRI to examine brain activity in experienced, female AVG players during visually-guided reaching. In the second, we examine the kinematics of visually-guided reaching in this population. Imaging data demonstrate that relative to women who do not play, AVG players have less motor-related preparatory activity in the cuneus, middle occipital gyrus, and cerebellum. This decrease is correlated with estimates of time spent playing. Further, these correlations are strongest during the performance of a visuomotor mapping that spatially dissociates eye and arm movements. However, further examinations of the full time-course of visuomotor-related activity in the AVG players revealed that the decreased activity during motor preparation likely results from a later onset of activity in AVG players, which occurs closer to beginning motor execution relative to the non-playing group. Further, the data presented here suggest that this later onset of preparatory activity represents greater neural efficiency that is associated with faster visually-guided responses.


Theoretical study of the D-->C emission spectrum of NO(2).
The 3 (2)A(')(D)-->1 (2)A(")(C) emission spectrum of NO(2) has been calculated by means of exact dynamics calculations and an accurate potential energy surface for the C state. The potential energy surface has been obtained by electronic structure calculations employing the internally contracted multireference configuration interaction method plus Davidson correction and the augmented correlation consistent polarized quadruple zeta basis set. The calculated spectrum, based on energies as well as intensities, agrees well with the measured one. Despite the two asymmetric C(s) potential wells of the C potential energy surface, the spectrum is best described by a C(2v) assignment in terms of symmetric stretch, bending, and antisymmetric stretch quantum numbers. The barrier separating the two wells is merely of the order of 500 cm(-1) with the consequence that only the two lowest states, (0,0,0) and (0,0,1), show a tunneling splitting. Essential for the correct assignment of the spectrum is the pronounced negative anharmonicity of the antisymmetric stretch mode. Excitation of the symmetric stretch mode is not directly seen in the main part of the spectrum.


Diagnostic test for lymphoproliferative disease virus infection of turkeys, using the polymerase chain reaction.
Lymphoproliferative disease virus, a type-C retrovirus, is the etiologic agent of a naturally acquired lymphoproliferative disorder in turkeys. The disease is characterized by rapid induction of lymphoproliferative lesions with morphologic and histopathologic features resembling those of reticuloendotheliosis. Owing to lack of overt clinical manifestations, early detection of lymphoproliferative disease virus is essential for preventing the rapid horizontal spread of the disease that can decimate flocks. We describe development of a simple, rapid, sensitive, and highly specific assay, using the polymerase chain reaction, capable of providing differential diagnosis of the disease soon after infection.


Evaluation of a Nurse-Initiated Acute Gastroenteritis Pathway in the Pediatric Emergency Department.
Acute gastroenteritis (AGE) is a common illness treated in the emergency department. Delays in initiating rehydration for children with mild or moderate dehydration from AGE can lead to prolonged ED visits and increased resource utilization that do not provide prognostic value or support family-centered care. The purpose of this quality improvement project was to promote early oral rehydration therapy (ORT) for persons with AGE in an attempt to reduce unnecessary resource utilization and length of stay (LOS). This prospective quality improvement project used a nurse-initiated waiting room ORT pathway for patients 6 months to 21 years of age who presented to the emergency department with diarrhea with or without vomiting. Outcomes related to nurse-initiated ORT, intravenous fluid use, laboratory studies or diagnostic imaging, and LOS were measured before and after implementation. Of 643 patients for whom the pathway was initiated, 392 received nurse-initiated care. The proportion of intravenous fluid use was 10.2% lower (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.27-0.68) and laboratory test ordering was 7.4% lower (OR, 0.64; 95% CI, 0.43-0.94) in patients receiving nurse-initiated care. Time to discharge after provider examination was 46 minutes faster in the nurse-initiated care group (P < .001), resulting in an overall LOS reduction by 40 minutes (P < .001). Nurse autonomy in using an AGE pathway facilitates evidence-based practice, improves ED efficiency, and decreases resource utilization and LOS. Future research should focus on family satisfaction and ED revisits within 72 hours of discharge.


Pediatric education in emergency medicine residency programs--10 years later.
The purpose of this study is to examine the changes in the pediatric emergency medicine education of emergency medicine (EM) residents over the last decade. Questionnaires were mailed to the training directors of all EM residency programs. Sixty-five programs (79%) responded. While children represent 29 +/- 2% of all patients seen in the institutions surveyed, only 17 programs (26%) provide more than six months of pediatric education, ie, no increase in the last decade. EM residents frequently rotate through pediatric emergency departments (72%), inpatient pediatric wards (51%), and pediatric intensive care units (88%). Most physicians in charge of pediatric emergency medicine education are emergency medicine trained (75% vs 29% in 1981), and only 12% are pediatric emergency medicine fellowship trained. Despite several improvements and the increased satisfaction of program directors, the pediatric component of EM residents' training continues to be disproportionate to the number of children in the emergency medicine patient population. Specialists in pediatric emergency medicine should strive to play a more significant role in the pediatric education of EM residents.


Partially assembled K99 fimbriae are required for protection.
Antibodies to K99 fimbriae afford protection to F5+ bovine enterotoxigenic Escherichia coli (ETEC). Previous studies show that murine dams immunized with Salmonella vaccine vectors stably expressing K99 fimbriae confer protection to ETEC-challenged neonatal pups. To begin to address adaptation of the K99 scaffold to display heterologous B- and T-cell epitopes, studies were conducted to determine how much of the assembled K99 fimbria is required to maintain protective immunity. Sequential deletions in the K99 gene clusters were made, resulting in diminished localization of the K99 fimbrial subunit in the outer membrane. As placement of the K99 fimbrial subunit became progressively contained within the vaccine vector, diminished immunoglobulin A (IgA) and IgG1 antibody titers, as well as diminished Th2-type cytokine responses, were observed in orally immunized mice. Deletion of fanGH, which greatly reduced the export of the fimbrial subunit to the outer membrane, showed only partial reduction in protective immunity. By contrast, deletion of fanDEFGH, which also reduced the export of the fimbrial subunit to the outer membrane but retained more subunit in the cytoplasm, resulted in protective immunity being dramatically reduced. Thus, these studies showed that retention of K99 fimbrial subunit as native fimbriae or with the deletion of fanGH is sufficient to confer protection.


Effect of using stencil masks made by focused ion beam milling on permalloy (Ni81Fe19) nanostructures.
Focused ion beam (FIB) milling is a common fabrication technique to make nanostencil masks which has the unintended consequence of gallium ion implantation surrounding milled features in silicon nitride membranes. We observe major changes in film structure, chemical composition, and magnetic behaviour of permalloy nanostructures deposited by electron beam evaporation using silicon nitride stencil masks made by a FIB as compared to stencil masks made by regular lithography techniques. We characterize the stenciled structures and both types of masks using transmission electron microscopy, electron energy loss spectroscopy, energy dispersive x-ray spectroscopy, magnetic force microscopy and kelvin probe force microscopy. All these techniques demonstrate distinct differences at a length scale of a 1-100 nm for the structures made using stencil mask fabricated using a FIB. The origin of these differences seems to be related to the presence of implanted ions, a detailed understanding of the mechanism however remains to be developed.


New questions regarding bioequivalence of levothyroxine preparations: a clinician's response.
A recent decision by the Food and Drug Administration (FDA) to declare various brands of levothyroxine bioequivalent has provoked objections from several physicians' organizations. These organizations assert that the method of testing bioequivalence is flawed, and that indiscriminate switching among preparations could lead to serious instances of undertreatment and overtreatment of hypothyroid patients. In this review we first list common indications for thyroid hormone administration, distinguishing its use as replacement therapy in hypothyroidism from its use to suppress thyrotropin (TSH) secretion in cases of thyroid cancer, nodules, and goiter. The dangers associated with changing to a preparation with different bioavailability are summarized, noting the particular danger of giving a more active preparation to a patient receiving TSH-suppressive doses of levothyroxine. However, these dangers are part of a larger problem: there are data showing that large numbers of patients are already receiving an improper dosage of levothyroxine, as judged from measurements of serum TSH. The recent history of FDA actions concerning levothyroxine bioequivalence and the arguments of those in disagreement are summarized. The immediate response to these problems should be better education of both patients and physicians. It is also recommended that there be further discussion of the problems in determining bioequivalence, and that consideration be given to more accurate and clinically relevant methods. Such methods should include assessment of the changes in TSH induced by each preparation in athyrotic patients.


A method for sampling and tissue preparation of the parathyroid glands in miniature pigs for toxicity studies.
Miniature swine (minipigs) are often used in non-rodent toxicity studies. However, unlike other animal species, the parathyroid glands of minipigs are often covered with thymic tissue and are similar in color, making macroscopical identification difficult. We investigated a method for sampling and tissue preparation of the parathyroid glands using 5- to 7-month-old minipigs. The glands were identified by finding the insertion site of a branch from the carotid artery into the cervical part of the thymus. Then the glands were marked and sampled. In a preliminary study, the glands were macroscopically and microscopically detected in 3/8 animals. The glands were not identified macroscopically in 5/8 animals but were detected in 3 of these animals. In total, we succeeded in detection of the glands in 6/8 animals (75%). The method was applied in the main toxicity study, and we succeeded in 100% detection through technical advancement. The method described herein enables high rate of detection and is useful in the pathological evaluation of the parathyroid glands of minipigs.


Effects of elevated atmospheric CO2 concentrations on the quantitative protein composition of wheat grain.
The continuing increase in atmospheric CO 2 concentration is predicted to enhance biomass production and to alter biochemical composition of plant tissues. In the present study, winter wheat ( Triticum aestivum L. cv. 'Batis') was grown under ambient air (BLOW, CO 2 concentration: 385 muL L (-1)) and free-air CO 2 enrichment (FACE, CO 2 concentration: 550 muL l (-1)) and two different nitrogen (N) fertilization levels (normal N supply: N100, 50% of normal N supply: N50). Mature kernels were milled into white flour and analyzed for the contents of crude protein, Osborne fractions, single gluten protein types and glutenin macropolymer. Elevated CO 2 caused significant reductions in crude protein and all protein fractions and types ( p < 0.001) except albumins and globulins. Effects were more pronounced in wheat samples supplied with normal amounts of N fertilizer. Crude protein was reduced by 14% (N100) and 9% (N50), gliadins by 20% and 13%, glutenins by 15% and 15% and glutenin macropolymer by 19% and 16%, respectively. Within gliadins, omega5-gliadins (-35/-22%) and omega1,2-gliadins (-27/-14%) were more affected than alpha-gliadins (-21/-13%) and gamma-gliadins (-16/-12%). Within glutenins, HMW subunits (-23/-18%) were more affected than LMW subunits (-12/-15%). According to these results, flour from high CO 2 grown grain will have a diminished baking quality. To our knowledge, these are the first results of elevated CO 2 concentrations impacts on wheat grain protein composition gained under relevant growing conditions at least for Central Europe.


PHOSPHORUS DISTRIBUTION IN PLEUROPNEUMONIA-LIKE AND L-TYPE ORGANISMS.
Langenfeld, M. G. (University of South Dakota, Vermillion) and P. F. Smith. Phosphorus distribution in pleuropneumonia-like and L-type organisms. J. Bacteriol. 86:1216-1219. 1963.-Sterol-requiring and sterol-nonrequiring pleuropneumonia-like organisms, salt-requiring and salt-nonrequiring L forms, and their parent bacteria, were analyzed for total, acid-soluble, lipid, and nucleic acid phosphorus. Total phosphorus in all types of organisms was equivalent, except for salt-requiring L forms in which it was greatly elevated. The elevated total phosphorus reflected a great increase in acid-soluble phosphorus in the salt-requiring L forms. The lipid phosphorus content of pleuropneumonia-like organisms and salt-nonrequiring L forms was significantly greater than in the other types of organisms. The nucleic acid phosphorus content of salt-requiring L forms was lower than that of all other organisms


Model-free adaptive sliding mode control with adjustable funnel boundary for robot manipulators with uncertainties.
Considering that the nominal dynamics model or numerous parameters of robotics are usually unsuitable for real applications, a model-free adaptive sliding mode control with an adjustable funnel boundary is proposed for robot manipulators with uncertainties. First, time delay estimation (TDE) technique is utilized to estimate the unknown dynamics of the control system, which ensures an attractive model-free advantage. Furthermore, a modified funnel function is introduced to transform the trajectory tracking error fall within an adjustable funnel boundary strictly. Then, based on the transformed error variable, a novel funnel nonsingular fast terminal sliding mode control scheme is developed to enhance the transient and steady-state tracking performance of the closed-loop control system. To cope with the TDE error, an adaptive update method is designed with only one adaptive parameter, which is adaptively tuned according to the sliding surface. Finally, the simulation and experimental results are presented to illustrate the superiority and high-precision tracking performance of the proposed approach.


Umbilical cord prolapse: a 10-year retrospective study in two civil hospitals, North Jordan.
Umbilical cord prolapse (UCP) is an obstetric emergency. The objective of our study was to determine the frequency of cord prolapse, its aetiological factors and to evaluate fetal prognosis. This was a retrospective review of cord prolapse deliveries in the main two civil hospitals in North Jordan between 1995 and 2005, at Princess Badeea Hospital and at King Abdullah University Hospital (KAUH) in Irbid, North Jordan. There were 146 patients identified with UCP among a total of 64,192 consecutive births. The incidence of cord prolapse was one in 440 cases (146/64,192). It occurred mostly in women over 25 years, and significantly more in pre-term births, low birth weight babies, multigravida, and only a few were associated with induced cases. It was not associated with higher rates of perinatal mortality and this supports the benefit of clinical management of UCP by emergency (crash) delivery.


[Contribution to the microanatomy of the proximal part of the arteria centralis longa (Heubner's artery)].
The anterior communicating artery complex is one of the most frequent intracranial aneurysm sites. Pterional craniotomy is the usual way to expose this region. While exposing of the aneurysmal dome, the posterior part of the gyrus rectus is frequently resected. In this stage of the procedure and later during clipping of the aneurysm, the surgeon's manipulation is closely related to the proximal part of the Heubner's artery. This vessel feeds important structures in the region of the basal ganglia. The anatomy of the Heubner's artery was described by many authors. However the intraoperative identification of this artery is still not clear. Therefore we performed detailed microanatomical investigation of the proximal part of the Heubner's artery in 40 brain hemispheres. It was found that during resection of the posterior part of the gyrus rectus two arteries are exposed. The recurrent Heubner's artery runs posteriorly to the gyrus rectus. The second artery runs on the medial and inferior surface of gyrus rectus supplying cerebral cortex. This artery frequently originates from the A1/A2 junction or the proximal part of the A2 segment of the anterior cerebral artery. Because of it, this cortical artery is difficult to distinguish from the recurrent Heubner's artery. This artery can branch out from the recurrent Heubner's artery or the frontopolar artery. In conclusion, the greatest probability of the injury to the recurrent Heubner's artery may occur during resection of the posterior part of the gyrus rectus.


[A biomechanical study on different fixation of cortical bone plate allograft].
To explore the biomechanical difference between the different fixations of cortical bone plate allograft. Twenty-seven cadaveric femurs were harvested and were made into the simulated fracture models, which were equally divided into Groups A, B and C. In Group A, the models were fixed with 2 bone plate allografts (110 mm x 10 mm x 3 mm); in Group B, the models were fixed with 2 struts (110 mm x 10 mm x 3 mm) and 5 bone screws; in Group C, the models were fixed with 1 strut (110 mm X 10 mm x 3 mm) and 5 bone screws. The biomechanical tests for the three-piont bending, torsion, and compression were performed. The parameters studied included the values of the displacements in the three-piont bending tests and the compression tests, and the maximum loads during the bending, the compression, and the torsion. As for all the stiffness parameters tested, Group A showed the greatest displacements among the three groups (P<0.05), except the compressive stiffness parameter, which was similar to that in Group B. The maximum loads of the three-point bending, the torsion, and the compression in Group A were 1.65+/-0.34 kN, 554.3+/-49.34 N, and 7.78 +/-0.82 Nm, respectively; in Group B, they were 1. 12+/-0.37 kN, 428.00+/-37.40 N, and 3.39+/-0.22 Nm, respectively; in Group C, they were 0.71+/-0.46 kN, 218.67+/-36.53 N, and 1.74+/-0.12 Nm, respectively. Group A had a significantly greater strength than the other 2 groups (P< 0.05). The strength of the cortical bone plate allograft is related to its different fixations. The two cortical bone plate allografts have a greater strength and stiffness than the struts fixed with the bone screws, which can meet the clinical requirement.


Genes and genetics in eye diseases: a genomic medicine approach for investigating hereditary and inflammatory ocular disorders.
Past 25y have witnessed an exponential increase in knowledge and understanding of ocular diseases and their respective genetic underpinnings. As a result, scientists have mapped many genes and their variants that can influence vision and health of our eyes. Based on these findings, it is becoming clear that an early diagnosis employing genetic testing can help evaluate patients' conditions for instituting treatment plan(s) and follow-up care to avoid vision complications later. For example, knowing family history becomes crucial for inherited eye diseases as it can benefit members in family who may have similar eye diseases or predispositions. Therefore, gathering information from an elaborate examination along with complete assessment of past medical illness by ophthalmologists followed by consultation with geneticists can help create a roadmap for making diagnosis and treatment precise and beneficial. In this review, we present an update on ocular genomic medicine that we believe has tremendous potential towards unraveling genetic implications in ocular diseases and patients' susceptibilities. We also discuss translational aspects of genetic ophthalmology and genome engineering that may help advance molecular diagnostics and therapeutics.


Are subjective language complaints in memory clinic patients informative?
To diagnose mild cognitive impairment, it is crucial to understand whether subjective cognitive complaints reflect objective cognitive deficits. This question has mostly been investigated in the memory domain, with mixed results. Our study was one of the first to address it for language. Participants were 55-to-93-year-old memory clinic patients (n = 163). They filled in a questionnaire about subjective language and memory complaints and performed two language tasks (naming-by-definition and sentence comprehension). Greater language complaints were associated with two language measures, thus showing a moderate value in predicting language performance. Greater relative severity of language versus memory complaints was a better predictor, associated with three language performance measures. Surprisingly, greater memory complaints were associated with better naming, probably due to anosognosia in further disease progression or personality-related factors. Our findings highlight the importance of relative complaint severity across domains and, clinically, call for developing self-assessment questionnaires asking specific questions about multiple cognitive functions.


Emergency department presentations in palliative care patients: a retrospective cohort study.
To map the patient journey for individuals known to palliative care presenting to the emergency department (ED). A linked dataset from the CUREd database and palliative care services in a region in the North of England was used. The study describes day and time of presentations, events occurring in the ED, mode of leaving the department and length of hospital admissions for presentations occurring within 90 days of a contact with palliative care. Findings were compared with the wider population in the CUREd database. A significant proportion of individuals known to palliative care (29.4%) presented to the ED. Presentations typically occurred in working hours. Most presented by ambulance (84.4%) and were admitted to hospital (75.1%); these observations persisted across age groups. Most presentations involved investigations (88.5%) and/or treatment (84.1%). Palliative patients exhibit significant use of the ED; some have the potential to benefit from attendances, but there is a minority for whom ED is unlikely to have improved their care. Advance care planning and communication between services are important for empowering those who stand to benefit from ED, while ensuring appropriate care is planned for those who prefer to avoid presenting.


Design and modeling of an efficiency horizontal thermal micro-actuator with integrated piezoresistors for precise control.
An integrated system made up of a double-hot arm electro-thermal microactuator and a piezoresistor embedded at the base of the 'cold arm' is proposed. The electro-thermo-mechanical modeling and optimization is developed to elaborate the operation mechanism of the hybrid system through numerical simulations. For given materials, the geometry design mostly influences the performance of the sensor and actuator, which can be considered separately. That is because thermal expansion induced heating energy has less influence on the base area of the 'cold arm,' where is the maximum stress. The piezoresistor is positioned here for large sensitivity to monitor the in-plane movement of the system and characterize the actuator response precisely in real time. Force method is used to analyze the thermal induced mechanical expansion in the redundant structure. On the other hand, the integrated actuating mechanism is designed for high speed imaging. Based on the simulation results, the actuator operates at levels below 5 mA appearing to be very reliable, and the stress sensitivity is about 40 MPa per micron.


Physiological recordings from the zebrafish lateral line.
During sensory transduction, external physical stimuli are translated into an internal biological signal. In vertebrates, hair cells are specialized mechanosensory receptors that transduce sound, gravitational forces, and head movements into electrical signals that are transmitted with remarkable precision and efficiency to afferent neurons. Hair cells have a conserved structure between species and are also found in the lateral line system of fish, including zebrafish, which serve as an ideal animal model to study sensory transmission in vivo. In this chapter, we describe the methods required to investigate the biophysical properties underlying mechanosensation in the lateral line of the zebrafish in vivo from microphonic potentials and single hair cell patch-clamp recordings to single afferent neuron recordings. These techniques provide real-time measurements of hair-cell transduction and transmission following delivery of controlled and defined stimuli and their combined use on the intact zebrafish provides a powerful platform to investigate sensory encoding in vivo.


Does phosphorus influence performance of a native hemiparasite and its impact on a native legume?
Phosphorus (P) is an essential plant nutrient and can become limiting in terrestrial ecosystems where parasitic plant:host associations occur. Yet little is known on how P availability influences parasite performance and its impact on hosts. We investigated the performance of the Australian native stem hemiparasite Cassytha pubescens and its impact on the native leguminous shrub Acacia paradoxa in high or low P conditions in a glasshouse experiment. Infected plants had significantly lower total, shoot, root and nodule biomass and shoot:root ratio than uninfected plants, regardless of P supply. The significant negative effect of infection on arbuscular mycorrhizal colonisation of host roots was more severe in the high P treatment. Infection significantly decreased predawn quantum yield of A. paradoxa in low P but not high P conditions. This finding may be due to the parasite-induced significant enrichment of aluminium in host foliage in low P but not high P treatments. A. paradoxa had significantly lower foliar phosphorus concentration [P] and nitrogen concentration in low P than high P conditions. Parasite biomass and photosynthetic performance were unaffected by P, whereas C. pubescens had significantly lower stem [P] in the low P than high P treatment. Parasite carbon isotope composition was significantly higher than that of the host, especially in low P conditions. Our results show that: (a) native parasite growth and its negative impact on growth of this native shrub was unaffected by P supply and (b) soil P conditions may have no influence on stem hemiparasite:host associations in nature.


Rapid analysis of mitochondrial DNA depletion by fluorescence in situ hybridization and immunocytochemistry: potential strategies for HIV therapeutic monitoring.
Nucleoside reverse transcriptase inhibitors (NRTIs) have been a mainstay in the treatment of human immunodeficiency virus since the introduction of azidothymidine (AZT) in 1987. However, none of the current therapies can completely eradicate the virus, necessitating long-term use of anti-retroviral drugs to prevent viral re-growth. One of the side effects associated with long-term use of NRTIs is mitochondrial toxicity stemming from inhibition of the mitochondrial DNA (mtDNA) polymerase gamma, which leads to mtDNA depletion and consequently to mitochondrial dysfunction. Here we report the use of fluorescence in situ hybridization (FISH) and immunocytochemistry (ICC) to monitor mtDNA depletion in cultured fibroblasts treated with the NRTI 2',3'-dideoxycytidine (ddC). These techniques are amenable to both microscopy and flow cytometry, allowing analysis of populations of cells on a single-cell basis. We show that, as mtDNA depletion progresses, a mosaic population develops, with some cells being depleted of and others retaining mtDNA. These techniques could be useful as potential therapeutic monitors to indicate when NRTI therapy should be interrupted to prevent mitochondrial toxicity and could aid in the development of less toxic NRTIs by providing an assay suitable for pharmacodynamic evaluation of candidate molecules.


Multidrug resistance protein. Identification of regions required for active transport of leukotriene C4.
Multidrug resistance protein (MRP) is a broad specificity, primary active transporter of organic anion conjugates that confers a multidrug resistance phenotype when transfected into drug-sensitive cells. The protein was the first example of a subgroup of the ATP-binding cassette superfamily whose members have three membrane-spanning domains (MSDs) and two nucleotide binding domains. The role(s) of the third MSD of MRP and its related transporters is not known. To begin to address this question, we examined the ability of various MRP fragments, expressed individually and in combination, to transport the MRP substrate, leukotriene C4 (LTC4). We found that elimination of the entire NH2-terminal MSD or just the first putative transmembrane helix, or substitution of the MSD with the comparable region of the functionally and structurally related transporter, the canalicular multispecific organic anion transporter (cMOAT/MRP2), had little effect on protein accumulation in the membrane. However, all three modifications decreased LTC4 transport activity by at least 90%. Transport activity could be reconstituted by co-expression of the NH2-terminal MSD with a fragment corresponding to the remainder of the MRP molecule, but this required both the region encoding the transmembrane helices of the NH2-terminal MSD and the cytoplasmic region linking it to the next MSD. In contrast, a major part of the cytoplasmic region linking the NH2-proximal nucleotide binding domain of the protein to the COOH-proximal MSD was not required for active transport of LTC4.


Impulsive reaction to social distress.
Psycho-physiological studies suggest that social rejection leads to social distress and favours impulsivity. We therefore investigated changes in behavioural impulsivity after exposure to social rejection by taking into account impulsive personality traits and changes to affective states. 30 university students were recruited. The Go/No-go task assessed behavioural impulsivity, the Barratt Impulsiveness Scale measured impulsive personality traits, and Likert scales measured affective states. A video clip and a writing exercise were used to induce stress. We found that impulsive error responses increased significantly after exposure. Decreased level of excitement and of loneliness were reported after stress. Distress caused by social rejection increased impulsive behaviour, but the degree of this change could not be associated with trait impulsivity, and was reported subjectively.


Some physical factors influencing the accuracy of convolution scatter correction in SPECT.
Some important physical factors influencing the accuracy of convolution scatter correction techniques in SPECT are presented. In these techniques scatter correction in the projection relies on filter functions, QF, evaluated by Fourier transforms, from measured scatter functions, Qp, obtained from point spread functions. The spatial resolution has a marginal effect on Qp. Thus a single QF can be used in the scatter correction of SPECT measurements acquired with the low energy high resolution or the low energy general purpose collimators and over a wide range of patient-collimator distances. However, it is necessary to examine the details of the shape of point spread functions during evaluation of Qp. QF is completely described by scatter amplitude AF, slope BF and filter sum SF. SF is obtained by summation of the values of QF occupying a 31 x 31 pixels matrix. Regardless of differences in amplitude and slope, two filter functions are shown to be equivalent in terms of scatter correction ability, whenever their sums are equal. On the basis of filter sum, the observed small influence of ellipticity on QF implies that an average function can be used in scatter correcting SPECT measurements conducted with elliptic objects. SF is shown to increase with a decrease in photon energy and with an increase in window size. Thus, scatter correction by convolution may be severely hampered by photon statistics when SPECT imaging is done with low-energy photons. It is pointless to use unnecessarily large discriminator windows, in the hope of improving photon statistics, since most of the extra events acquired will eventually be subtracted during scatter correction. Regardless of the observed moderate reduction in SF when a lung-equivalent material replaces a portion of a water phantom, further studies are needed to develop a technique that is capable of handling attenuation and scatter corrections simultaneously. Whenever superficial and inner radioactive distributions coexist the observed reduction of SF close to the phantom surface indicates that scatter correction of such distributions has to rely on two distinct filter functions. Corrections based on a surface function produce accurate results in the superficial region, while the central distributions are substantially overestimated. Surface radioactive distributions introduce appreciable errors in the determination of central distributions when corrections are based on central filter function. This function introduces a reduction of about 40% in the measured surface concentration.


The carbon fertilization effect over a century of anthropogenic CO2 emissions: higher intracellular CO2 and more drought resistance among invasive and native grass species contrasts with increased water use efficiency for woody plants in the US Southwest.
From 1890 to 2015, anthropogenic carbon dioxide emissions have increased atmospheric CO2 concentrations from 270 to 400 mol mol-1 . The effect of increased carbon emissions on plant growth and reproduction has been the subject of study of free-air CO2 enrichment (FACE) experiments. These experiments have found (i) an increase in internal CO2 partial pressure (ci ) alongside acclimation of photosynthetic capacity, (ii) variable decreases in stomatal conductance, and (iii) that increases in yield do not increase commensurate with CO2 concentrations. Our data set, which includes a 115-year-long selection of grasses collected in New Mexico since 1892, is consistent with an increased ci as a response to historical CO2 increase in the atmosphere, with invasive species showing the largest increase. Comparison with Palmer Drought Sensitivity Index (PDSI) for New Mexico indicates a moderate correlation with Δ13 C (r2 = 0.32, P < 0.01) before 1950, with no correlation (r2 = 0.00, P = 0.91) after 1950. These results indicate that increased ci may have conferred some drought resistance to these grasses through increased availability of CO2 in the event of reduced stomatal conductance in response to short-term water shortage. Comparison with C3 trees from arid environments (Pinus longaeva and Pinus edulis in the US Southwest) as well as from wetter environments (Bromus and Poa grasses in New Mexico) suggests differing responses based on environment; arid environments in New Mexico see increased intrinsic water use efficiency (WUE) in response to historic elevated CO2 while wetter environments see increased ci . This study suggests that (i) the observed increases in ci in FACE experiments are consistent with historical CO2 increases and (ii) the CO2 increase influences plant sensitivity to water shortage, through either increased WUE or ci in arid and wet environments, respectively.


The Effect of External Approach Septoplasty on Olfactory Function.
Septal deviation-induced nasal obstruction is frequently accompanied by hyposmia. The aim of this study was to evaluate the effect of external approach septoplasty on olfactory function. Thirty patients (23 males, 7 females) who had external approach septoplasty were included in the study. The age interval was 18 to 60 years (mean 33±12 years). All subjects had olfactory function and acoustic rhinometry tests in both the pre- and postoperative periods (mean interval 6 weeks ± 3 weeks). Olfactory function was determined by the "Sniffin Sticks" test. The minimum cross-sectional area from the nostril to 2.20 cm backward was referred to as MCA1, and the minimum cross-sectional area from 2.20 to 5.40 cm was referred to as MCA2, determined by acoustic rhinometry. Olfactory threshold, discrimination, and identification function improved significantly after external approach septoplasty. A statistically significant difference was also detected between pre- and postoperative left MCA1 and left MCA2 of the nasal cavities. Postoperative hyposmic and anosmic patient improvement was statistically significant. External approach septoplasty has a beneficial effect on olfaction and this effect may be partly due to interactions between the increased perception of nasal air flow, as well as surgery-associated improvement in the internal nasal valve area.


Avoiding type III, IV, and V errors through collaborative research.
Major types of empirical errors reviewed by a number of leading research textbooks include discussions of Type I and Type II errors. However, applied human service researchers can commit other types of errors that should be avoided. The potential benefits of the applied, collaborative research (in contrast to traditional participatory research) include an assurance that the study begins with the "right" questions that are important for community residents. Such research practice also helps generate useful research findings for decisions regarding redistribution of resources and resolving community issues. The aim of collaborative research is not merely to advance scientific understanding, but also to produce empirical findings that are usable for addressing priority needs and problems of distressed communities. A review of a case example (Garfield Community Assessment Study) illustrates the principles and practices of collaborative research.


Advocacy for neuropsychology in the public sector: the VA experience.
In this paper important advocacy areas for the VA are described with implications for other psychologists working in institutional settings in the public sector, and some advice is provided concerning how best to advocate in the VA. Distinctions among advocacy issues that are of concern to the general public, those that are of concern to all psychologists involved in healthcare, and those specifically related to clinical neuropsychology are made.


Treatment of carotid cavernous fistulas using covered stents: midterm results in seven patients.
Carotid cavernous fistulas (CCF) can be effectively treated by using different therapeutic alternatives such as detachable balloons and detachable coils, alone or in combination with N-butyl-2-cyanoacrylate (n-BCA) or Onyx. Stents have also been used in an attempt to improve preservation of the parent artery while still occluding the fistula. We present our experience using balloon-expandable covered stents to treat CCF, focusing on arterial wall reconstruction. To our knowledge, this is the first series with midterm follow-up between 3 months and 3.5 years. From the 46 CCF treated at our institution between November 1998 and September 2006, a total of 7 posttraumatic direct CCF were treated using polytetrafluoroethylene (PTFE)-covered stents between April 2003 and September 2006. Five were treated with covered stents alone. One patient with transection of the internal carotid artery (ICA) first underwent bare stent placement to provide support for the covered stent. One patient had to be treated with coils and n-BCA. Control angiograms obtained in the 7 patients demonstrated occlusion of the fistula and preservation of the ICA in all cases. There was no mortality and no immediate postprocedural morbidity. There was 1 case of morbidity identified at 1-month follow-up with asymptomatic occlusion of the ICA; the other 6 patients had angiographic follow-up between 3 and 42 months (mean, 18.4 months), with persistent occlusion of the fistulas, patent stent grafts, and no significant intimal hyperplasia. PTFE-covered stents are evolving as a promising intracranial therapeutic alternative to treat CCF and preserve the parent artery by reconstructing the arterial wall. They should be considered in patients in whom fistulas cannot be successfully occluded with detachable balloons or detachable coils. More investigation is required to further develop their specifications and indications.


An efficient synthesis of the new benzo[c]pyrido[2,3,4-kl]acridine skeleton.
A series of molecules of therapeutic interest, possessing the new skeleton of 1H-benzo[c]pyrido[2,3,4-kl]acridine with acyl or aminoacyl and methoxy or aminoalkoxy substituents on the aromatic homocycles were synthesized by means of a Friedländer-type reaction. The requisite 5-aminodihydroquinoline-4-ones 1, whose preparation is described, were reacted with the appropriate alpha-tetralones 2 using an acidic catalyst (PPTS) under azeotropic conditions. Optimized reaction time and yield depend on temperature, which must not be below 90 degrees C.


The role of chorion on toxicity of silver nanoparticles in the embryonic zebrafish assay.
This study was designed to investigate how the size- and surface coating-dependent toxicity of silver nanoparticles (AgNPs) is influenced by the presence and absence of the chorion in an embryonic zebrafish assay. Normal and dechorinated embryos were exposed to four different AgNPs, 20 or 110 nm in size, with polypyrrolidone (PVP) or citrate surface coatings in a standard zebrafish embryo medium (EM). This was then compared to a 62.5 μM calcium chloride (CaCl2) solution where agglomeration was controlled. Embryonic toxicity in the absence of the chorion was greater than in its presence. The smaller 20 nm AgNPs were more toxic than the larger 110 nm AgNPs, regardless of the chorion and test media. However, surface coating affected toxicity, since PVPcoated AgNPs were more toxic than citrate-coated AgNPs; this was strongly affected by the presence of the chorion in both EM and CaCl2. Our results demonstrate the permeability function of the chorion on the size- and surface coating-dependent toxicity of AgNPs. Thereafter, careful experiment should be conducted to assess nanoparticle toxicity in zebrafish embryos.


Prediction of hERG Potassium Channel Blocking Actions Using Combination of Classification and Regression Based Models: A Mixed Descriptors Approach.
A set of 242 compounds with diverse molecular structures and having different mechanisms of therapeutic actions was used to develop classification and regression based QSAR models for the identification of potential hERG channel blockers. The developed in silico models made it possible to obtain a quantitative interpretation of the structural information and physicochemical properties of the molecules for their hERG binding affinity along with exploration of the discriminant functions differentiating between lower and higher hERG blocking potency compounds by the classification approach. The developed models were rigorously validated internally as well as externally with the application of the principles of Organization for Economic Cooperation and Development (OECD) for the validation purpose. The test for domain of applicability was also carried out for checking reliability of the predictions. Pharmacological distribution diagrams (PDDs) were employed as a visualizing technique for the classification approach. Important fragments relevant to hERG binding affinity were identified through critical analysis and interpretation of the developed models. Finally, the developed models were implemented to screen hERG channel blocking properties for a huge number compounds of the DrugBank database. In silico prediction for hERG channel blocking potential for each of the DrugBank compounds is possible from the developed models.


Low voltage electrocardiogram after acute myocardial infarction.
In a retrospective study of patients with acute myocardial infarction admitted to a coronary monitoring unit in 1971 12 per cent (39 patients) had low voltage electrocardiograms within 72 hours of admission. Of these, 7 patients (18%) died while in hospital and a further 9 (23%) died within one year of their infarction. Of the 23 patients who survived, 16 were severely incapacitated by their symptoms at the one-year follow-up. A low voltage electrocardiogram in association with acute myocardial infarction appears to imply a poor prognosis in terms of both mortality and morbidity, independently of other prognostic indices.


Microdevices in mass spectrometry.
Miniaturization of laboratory instrumentation is becoming critical in achieving the speed and throughput required by the current revolutionary progress in biology. This mini review critically summarizes the present status of microfluidic devices designed for use in mass spectrometry.


Quantitatively assessing mekosuchine crocodile locomotion by geometric morphometric and finite element analysis of the forelimb.
Morphological shifts observed in the fossil record of a lineage potentially indicate concomitant shifts in ecology of that lineage. Mekosuchine crocodiles of Cenozoic Australia display departures from the typical eusuchian body-plan both in the cranium and postcranium. Previous qualitative studies have suggested that these crocodiles had a more terrestrial habitus than extant crocodylians, yet the capacity of mekosuchine locomotion remains to be tested. Limb bone shape, such as diaphyseal cross-section and curvature, has been related to habitual use and locomotory function across a wide variety of taxa. Available specimens of mekosuchine limbs, primarily humeri, are distinctly columnar compared with those of extant crocodylians. Here we apply a quantitative approach to biomechanics in mekosuchine taxa using both geomorphic morphometric and finite element methods to measure bone shape and estimate locomotory stresses in a comparative context. Our results show mekosuchines appear to diverge from extant semi-aquatic saltwater and freshwater crocodiles in cross-sectional geometry of the diaphysis and generate different structural stresses between models that simulate sprawling and high-walk gaits. The extant crocodylians display generally rounded cross-sectional diaphyseal outlines, which may provide preliminary indication of resistance to torsional loads that predominate during sprawling gait, whereas mekosuchine humeri appear to vary between a series of elliptical outlines. Mekosuchine structural stresses are comparatively lower than those of the extant crocodylians and reduce under high-walk gait in some instances. This appears to be a function of bending moments induced by differing configurations of diaphyseal curvature. Additionally, the neutral axis of structural stresses is differently oriented in mekosuchines. This suggests a shift in the focus of biomechanical optimisation, from torsional to axial loadings. Our results lend quantitative support to the terrestrial habitus hypothesis in so far as they suggest that mekosuchine humeri occupied a different morphospace than that associated with the semi-aquatic habit. The exact adaptational trajectory of mekosuchines, however, remains to be fully quantified. Novel forms appear to emerge among mekosuchines during the late Cenozoic. Their adaptational function is considered here; possible applications include navigation of uneven terrain and burrowing.


Triterpenoid saponins from root bark of Zanha golungensis (Sapindaceae).
The chemical investigation of the methanolic extract from root bark of Zanha golungensis Hiern led to the isolation of five new and one known triterpenoid saponins. Their structures were elucidated by full analysis of their spectroscopic data and by partial hydrolysis. These glycosides contain zanhic acid as aglycone, a rare oleanane-type triterpenoid found in species belonging to Sapindaceae, Caryophyllaceae, Asteraceae, and Fabaceae. Two new saponins are esterified saponins by 3,3-dimethylacryloyl and 3-hydroxy-2-methyl-butanoyl residues located on the sugar part. The new compounds were named zanhasaponins D-H following previous isolation of similar compounds from Zanha africana.


Effects of anti-inflammatory drugs on the expression of tryptophan-metabolism genes by human macrophages.
Several lines of evidence link macrophage activation and inflammation with (monoaminergic) nervous systems in the etiology of depression. IFN treatment is associated with depressive symptoms, whereas anti-TNFα therapies elicit positive mood. This study describes the actions of 2 monoaminergic antidepressants (escitalopram, nortriptyline) and 3 anti-inflammatory drugs (indomethacin, prednisolone, and anti-TNFα antibody) on the response of human monocyte-derived macrophages (MDMs) from 6 individuals to LPS or IFN-α. Expression profiling revealed robust changes in the MDM transcriptome (3294 genes at P < 0.001) following LPS challenge, whereas a more limited subset of genes (499) responded to IFNα. Contrary to published reports, administered at nontoxic doses, neither monoaminergic antidepressant significantly modulated the transcriptional response to either inflammatory challenge. Each anti-inflammatory drug had a distinct impact on the expression of inflammatory cytokines and on the profile of inducible gene expression-notably on the regulation of enzymes involved in metabolism of tryptophan. Inter alia, the effect of anti-TNFα antibody confirmed a predicted autocrine stimulatory loop in human macrophages. The transcriptional changes were predictive of tryptophan availability and kynurenine synthesis, as analyzed by targeted metabolomic studies on cellular supernatants. We suggest that inflammatory processes in the brain or periphery could impact on depression by altering the availability of tryptophan for serotonin synthesis and/or by increasing production of neurotoxic kynurenine.


Chlorophyllide-a-Oxygenase (CAO) deficiency affects the levels of singlet oxygen and formation of plasmodesmata in leaves and shoot apical meristems of barley.
In plants, organogenesis and specification of cell layers and tissues rely on precise symplastic delivery of regulatory molecules via plasmodesmata. Accordingly, abundance and aperture of plasmodesmata at individual cell boundaries should be controlled by the plant. Recently, studies in Arabidopsis established reactive oxygen species as major regulators of plasmodesmata formation and gating. We show that in a barley mutant deficient in the synthesis of chlorophyll b, the numbers of plasmodesmata in leaves and in the shoot apical meristem are significantly higher than in the corresponding wild type, probably due to redox imbalance in the mutant. The resulting disturbance of symplasmic transport is likely to be the reason for the observed delayed floral transition in these mutants.