Small and large wetland fragments are equally suited breeding sites for a ground-nesting passerine.
Large habitat fragments are generally thought to host more species and to offer more diverse and/or better quality habitats than small fragments. However, the importance of small fragments for population dynamics in general and for reproductive performance in particular is highly controversial. Using an information-theoretic approach, we examined reproductive performance and probability of local recruitment of color-banded reed buntings Emberiza schoeniclus in relation to the size of 18 wetland fragments in northeastern Switzerland over 4 years. We also investigated if reproductive performance and recruitment probability were density-dependent. None of the four measures of reproductive performance (laying date, nest failure probability, fledgling production per territory, fledgling condition) nor recruitment probability were found to be related to wetland fragment size. In terms of fledgling production, however, fragment size interacted with year, indicating that small fragments were better reproductive grounds in some years than large fragments. Reproductive performance and recruitment probability were not density-dependent. Our results suggest that small fragments are equally suited as breeding grounds for the reed bunting as large fragments and should therefore be managed to provide a habitat for this and other specialists occurring in the same habitat. Moreover, large fragments may represent sinks in specific years because a substantial percentage of all breeding pairs in our study area breed in large fragments, and reproductive failure in these fragments due to the regularly occurring floods may have a much stronger impact on regional population dynamics than comparable events in small fragments.


Collision dynamics and reactive uptake of OH radicals at liquid surfaces of atmospheric interest.
The inelastic scattering of OH radicals from the surfaces of a sequence of potentially reactive organic liquids: squalane (C(30)H(62), 2,6,10,15,19,23-hexamethyltetracosane); squalene (C(30)H(50), trans-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene); and oleic acid (C(18)H(34)O(2), cis-9-octadecanoic acid) was studied experimentally. A liquid long-chain perfluorinated polyether (PFPE, Krytox® 1506) was compared as a chemically inert reference. Gas-phase OH with an average laboratory-frame kinetic energy of 54 kJ mol(-1) was generated by 355-nm photolysis of a low-pressure of HONO a short distance (9 mm) above the liquid surface. Scattered OH was detected at the same distance by laser-induced fluorescence (LIF). Appearance profiles as a function of photolysis-probe delay were recorded for selected OH v' = 0, N' rotational levels. The efficiency of momentum transfer to the surface is least for PFPE and highest for squalane, with squalene and oleic acid intermediate, but in all cases the speed distributions are markedly too hot to be consistent with a thermal accommodation mechanism. The rotational distribution is found to be a function of scattered OH speed. The generally high rotational temperatures implied by the relative fluxes for N' = 1 and 5 were confirmed by LIF excitation spectra at the peak of the profile for each liquid. The trends in translational-to-rotational energy transfer were broadly consistent with the sequence in surface stiffness inferred from the translational inelasticity. The non-statistical distribution of OH fine-structure and Λ-doublet states produced by HONO photolysis appears to be effectively completely scrambled in collisions with the liquid surfaces. With due account taken of the product rotational distributions, and assuming that 100% of the OH scatters from PFPE, the integrated OH survival probabilities were: squalane (0.70 ± 0.08), squalene (0.61 ± 0.07) and oleic acid (0.76 ± 0.10). The 'missing' OH is presumed to have reacted at the liquid surface. Detailed comparison of the appearance profiles suggests that the main difference between squalane and squalene is loss of slower-moving OH, consistent with an additional capture mechanism at the vinyl sites.


Observation of a unique pattern of bifurcated hydrogen bonds in the crystal structures of the N-glycoprotein linkage region models.
Elucidation of the intra- and intermolecular carbohydrate-protein interactions would greatly contribute toward obtaining a better understanding of the structure-function correlations of the protein-linked glycans. The weak interactions involving C-H...O have recently been attracting immense attention in the domain of biomolecular recognition. However, there has been no report so far on the occurrence of C-H...O hydrogen bonds in the crystal structures of models and analogs of N-glycoproteins. We present herein an analysis of C-H...O interactions in the crystal structures of all N-glycoprotein linkage region models and analogs. The study reveals a cooperative network of bifurcated hydrogen bonds consisting of N-H...O and C-H...O interactions seen uniquely for the models. The cooperative network consists of two antiparallel chains of bifurcated hydrogen bonds, one involving N1-H, C2'-H and O1' of the aglycon moiety and the other involving N2-H, C1-H and O1'' of the sugar. Such bifurcated hydrogen bonds between the core glycan and protein are likely to play an important role in the folding and stabilization of proteins.


Risk factors for carbapenem resistant bacteraemia and mortality due to gram negative bacteraemia in a developing country.
To identify the risk factors for carbapenem resistant bacteraemia and mortality due to gram negative bacteraemia in a developing country. A prospective cohort study was conducted at the Sindh Institute of Urology and Transplantation (SIUT) from June to October 2012. Hospitalized patients > 15 years of age with gram negative bacteraemia were included and followed for a period of 2 weeks for in hospital mortality. Data was collected and analyzed for 243 subjects. Multivariate analysis was used to determine the risk factors for carbapenem resistant bacteraemia and mortality due to gram negative bacteraemia. Crude and adjusted odds ratio and 95% CI are reported. A total of 729 out of 1535 (47.5%) cultures were positive for gram negative isolates. Out of 243 subjects, 117 (48%) had an MDR isolate. Having an MDR isolate on culture (AOR, 2.33; 95% CI, 1.35-4.0), having multiple positive cultures (AOR, 1.8; 95% CI, 0.94-3.4) and stay in ICU > 48 hours (AOR, 2.0; 95% CI, 1.12-3.78) were identified as significant risk factors for mortality due to gram negative organisms. Risk factors for carbapenem resistant bacteraemia were age > 50 years (AOR, 1.83; 95% CI, 1.0-3.5), septic shock on presentation (AOR 2.53; 95% CI, 1.03-6.2), ICU stay of > 72 hours (AOR 2.40; 95% CI, 1.14-5.0) and receiving immunosuppressant medications (AOR 2.23; 95% CI, 0.74-6.7). There is a high burden of MDR and carbapenem resistant gram negative bacteraemia, with a high mortality rate.


Utility of dexmedetomidine in sedation for radiofrequency ablation of atrial fibrillation.
The utility of dexmedetomidine (DEX) as an adjunct to conventional procedural sedation using midazolam and fentanyl was evaluated in 11 adult patients undergoing radiofrequency catheter ablation (RFCA) of atrial fibrillation. In a subsequent comparison to 11 demographically matched controls (n = 22) that previously received only midazolam- and fentanyl-based sedation, no significant differences in consumption of midazolam (median, 5 vs 10 mg; P = .3), fentanyl (median, 275 vs 400 mcg, P = .2), respiratory parameters, and procedural outcome were found. However, median reductions of arterial blood pressure were significant: systolic (-26.1 vs -16.7 mm Hg, P = .006), diastolic (-26.7 vs -2.9 mm Hg, P = .01), and mean (-25.8 vs -8.5 mm Hg, P = .006). Reductions of blood pressure limited utility of DEX as adjunct in sedation for RFCA of atrial fibrillation.


Glial lesion of the infratemporal fossa presenting as a soft tissue middle ear mass - rudimentary encephalocele or neural crest remnant?
We report about ectopic glial tissue of the skull base and the parapharyngeal space presenting as a soft tissue mass in the middle ear. An 11-year-old boy presented with bilateral conductive hearing loss since early childhood. The history included previously removed lesions consistent with ectopic neuroglial tissue of the tongue and the parapharyngeal space soon after birth, as well as surgery for cleft palate. High resolution computed tomography of the petrous bone and magnetic resonance imaging were useful in identifying the skull base defect and in characterizing the lesion's relation to the brain. There was no clinical, radiological or surgical evidence of any associated dural defect. The lesion was removed via a modified infratemporal approach. Histology revealed neuroglial tissue with calcifications without any signs of mesodermal or entodermal origin. On the basis of this case the pathogenesis and diagnosis of ectopic brain tissue and its relation to the more commonly encountered meningoencephalic herniations are reviewed. Furthermore therapeutical implications are discussed.


[Value of intravenous nitroglycerin in hypertension after extracorporeal circulation].
The authors compare the haemodynamic effects of intravenous nitroglycerin (IV TNT) in 14 patients developing hypertension (mean blood pressure greater than 90 mmHg) and in seven normotensive patients (70 less than mean blood pressure less than 90 mmHg) after cardiac surgery with extracorporeal circulation (ECC). TNT was administered at doses of 0.5, 1, 2 microgram.kg-1.min-1 then 2 microgram.kg-1.min-1 with the association of vascular filling in order to restore right and left arterial pressures to their initial values. Various haemodynamic parameters were measured or calculated. The results obtained: in the hypertensive patients, at the low dose (0.5 microgram.kg-1.min-1) a prevalent venodilatory action was noted: RAP: 7.64 +/- 2.76 p less than 0.05; LAP: 9.07 +/- 3.19 p less than 0.05; at the middle dose (1 microgram.mg-1.min-1) venodilation continued resulting in a fall in BP 95.28 +/- 26.11 p less than 0.01 and above all in Cl: 2.28 +/- 0.36 p less than 0.01; at the maximum dose used, the action of TNT affected both the venous and arteriolar sector causing a major fall in BP: 89.64 +/- 23.88 p less than 0.001, in Cl: 2.29 +/- 0.33 p less than 0.01 and above all RVSI: 19.94 +/- 6.24 p less than 0.05. The association of vascular filling led to an increase in RAP and LAP (p = NS), Cl (p = NS) whilst BP remained low: 92.78 +/- 17.56 p less than 0.001 and also RVSI: 18.12 +/- 4.44 p less than 0.01. In the normotensive patients the administration of TNT, whatever the dose used, did not cause any significant changes (p = NS). In conclusion, the authors emphasise the value of the use of TNT in postoperative hypertensive states, in particular when associated with myocardial ischaemia.


In vivo effects of carprofen, deracoxib, and etodolac on prostanoid production in blood, gastric mucosa, and synovial fluid in dogs with chronic osteoarthritis.
To evaluate in vivo activity of carprofen, deracoxib, and etodolac on prostanoid production in several target tissues in dogs with chronic osteoarthritis. 8 dogs with chronic unilateral osteoarthritis of the stifle joint. Each dog received carprofen, deracoxib, or etodolac for 10 days with a 30- to 60-day washout period between treatments. On days 0, 3, and 10, prostaglandin (PG) E2 concentrations were measured in lipopolysaccharide-stimulated blood, synovial fluid, and gastric mucosal biopsy specimens; PGE1 concentrations were measured in gastric mucosal biopsy specimens; and thromboxane B2 (TXB2) was evaluated in blood. Carprofen and deracoxib significantly suppressed PGE2 concentrations in blood at days 3 and 10, compared with baseline, whereas etodolac did not. None of the drugs significantly suppressed TXB2 concentrations in blood or gastric PGE1 synthesis at any time point. All 3 drugs significantly decreased gastric synthesis of PGE2 at day 3 but not day 10 of each treatment period. All 3 drugs decreased synovial fluid PGE2 concentrations in the affected and unaffected stifle joints at days 3 and 10. Results indicate that carprofen and deracoxib act in vivo on target tissues as COX-1-sparing drugs by sparing gastric PGE1 and PGE2 synthesis and production of TXB2 by platelets. Etodolac also appears to be COX-1 sparing but may have variable effects on COX-2 depending on the tissue. In gastric mucosa and synovial fluid, there were no significant differences in PG production between compounds at recommended concentrations.


Gene-modified mesenchymal stem cells express functionally active nerve growth factor on an engineered poly lactic glycolic acid (PLGA) substrate.
Delivery of cellular and/or trophic factors to the site of injury may promote neural repair or regeneration and return of function after peripheral nerve or spinal cord injury. Engineered scaffolds provide a platform to deliver therapeutic cells and neurotrophic molecules. We have genetically engineered mesenchymal stem cells (MSCs) from the green rat (CZ-004 [SD TgN(act-EGFP)OsbCZ-004]) to express nerve growth factor (NGF) using an adenoviral vector. Cells maintained their stem cell phenotype as judged by expression of CD71 and CD172 markers, and absence of the hematopoietic marker CD45. Cells continued to express green fluorescent protein (GFP) on a long-term basis. Morphology, viability, and growth kinetics were maintained when cells were grown on a poly-lactic-co-glycolic acid (PLGA) polymer scaffold. Under appropriate growth conditions, they differentiated into chondrogenic, osteogenic, and adipogenic phenotypes, demonstrating that they retained their characteristics as MSCs. NGF was secreted from transduced MSCs at physiologically relevant levels ( approximately 25 ng/mL) measured by enzyme-linked immunoabsorbent assay (ELISA). Secreted NGF was functionally active in a neurite growth assay with PC12 cells. We conclude that MSCs are a good candidate for delivery of therapeutic factors into the injured nervous system. They are autologous, may be genetically modified to express neurotrophins, and are compatible with polymer surfaces that may be used as a potential delivery system.


A novel aspect of the information content of viroids.
Viroids were found to exhibit a structural periodicity characterized by repeat units of a length of 11 or 12 (potato spindle tuber viroid group and coconut cadang-cadang viroid), 60 (apple scar skin viroid) and 80 (avocado sunblotch viroid) nucleotide residues, respectively. It is suggested that structural periodicity of viroids is an indication of their protein-binding ability.


Methylnaltrexone: a novel approach for the management of opioid-induced constipation in patients with advanced illness.
In April 2008, the US FDA granted approval to methylnaltrexone (Relistor), the first peripheral micro-opioid-receptor antagonist for the treatment of opioid-induced constipation in advanced-illness patients receiving palliative care and for whom other laxative therapies failed to achieve adequate results. Methylnaltrexone, a quaternary derivative of naltrexone, introduces a novel mechanism of action that selectively antagonizes the peripheral micro-receptors in the GI tract without effects on the CNS. In clinical trials, subcutaneous methylnaltrexone reversed opioid-induced constipation after the first dose in approximately 50-60% of the patients. In most of the cases, effective laxation occurred within 1 h. The therapeutic benefit was sustained in multiple-dose studies. Owing to the nature of the population studied, safety data are available for approximately 4 months of use. Although it is not the focus of this article, methylnaltrexone's mechanism of action suggests it could be beneficial for other peripheral, opioid-induced adverse effects, such as opioid-related nausea, vomiting, urinary retention, pruritus or postoperative ileus.


Physical Characterization and Innate Immunogenicity of Aggregated Intravenous Immunoglobulin (IGIV) in an In Vitro Cell-Based Model.
To investigate in vitro the innate immune response to accelerated stress-induced aggregates of intravenous immunoglobulin (IGIV) using a well-defined human cell-line model, and to correlate the innate response to physical properties of the aggregates. IGIV aggregates were prepared by applying various accelerated stress methods, and particle size, count and structure were characterized. Immune cell activation as tracked by inflammatory cytokines released in response to aggregates was evaluated in vitro using peripheral blood mononuclear cells (PBMC), primary monocytes and immortalized human monocyte-like cell lines. IGIV aggregates produced by mechanical stress induced higher cytokine release by PBMC and primary monocytes than aggregates formed by other stresses. Results with the monocytic cell line THP-1 paralleled trends in PBMC and primary monocytes. Effects were dose-dependent, enhanced by complement opsonization, and partially inhibited by blocking toll-like receptors (TLR2 and TLR4) and to a lesser extent by blocking Fc gamma receptors (FcγRs). Stress-induced IGIV aggregates stimulate a dose-dependent cytokine response in human monocytes and THP-1 cells, mediated in part by TLRs, FcγRs and complement opsonization. THP-1 cells resemble primary monocytes in many respects with regard to tracking the innate response to IgG aggregates. Accordingly, the measurement of inflammatory cytokines released by THP-1 cells provides a readily accessible assay system to screen for the potential innate immunogenicity of IgG aggregates. The results also highlight the role of aggregate structure in interacting with the different receptors mediating innate immunity.


Pathogenesis of severe acute respiratory infections in the developing world: respiratory syncytial virus and parainfluenza viruses.
Respiratory syncytial virus (RSV) and parainfluenza viruses (PIVs) are the most frequently isolated pathogens in infants and children with acute lower respiratory infection (LRI) in the developed world. Less information is available about their importance in LRI in the developing world, but they are probably important there also. The pathogenesis of viral bronchiolitis and pneumonia involves inoculation and early replication in the upper respiratory tract, followed by aspiration into the lower respiratory tract when both the mucosal and systemic immune systems are involved in a specific response. Both disease and recovery reflect processes of viral replication (with attendant cellular destruction) and of immune response (with attendant direct cellular destruction and release of pathogenic, along with beneficial, mediators). Factors predisposing to bacterial superinfection are poorly understood except in animal models. Conditions leading to heightened susceptibility to severe disease in the developed world are particularly common in the developing world. Increasing information on RSV and PIV infections in the developing world will likely point to their importance. Strategies for prevention of severe illnesses due to these viruses will follow from concepts elucidated through animal models and studies of infants in the developed world.


[Cell death and neurogenesis after hypoxia: a brain repair mechanism in the developing rat?].
Perinatal brain damage following hypoxia-ischemia has long been considered irreversible, but recent rodent studies show that various insults can induce de novo neurogenesis in the adult brain. Here we examined whether acute hypoxia could trigger neurogenesis in the developing rat brain. In vitro, we examined the impact of transient hypoxia on cultured embryonic rat neurons. In vivo, we monitored the time course of brain damage in the CA1 layer of the hippocampus of one-day-old rats after exposure to hypoxia. The extent of cell loss and regeneration was evaluated after staining with DAPI. Newly generated cells were characterized in the subventricular zone by immunohistochemistry, 20 days post-exposure. The viability of cultured neurons was reduced by 36 % when measured 96 h after 6 h of hypoxia, and a significant number of cell nuclei showed apoptotic features. In contrast, cell numbers increased by 14 % 96 h after 3 h of hypoxia. The Bax/Bcl2 ratio tended to increase after 6 h of hypoxia and to decrease after 3 h of hypoxia. In the CA1 subfield of the hippocampus, hypoxia reduced the total number of cells by 27 % on day 6-7 post-reoxygenation, and histopathological hallmarks of apoptosis were observed This cell deficit was followed by gradual recovery, starting on day 20, suggesting a repair mechanism. BrdU incorporation in the subventricular zone showed an accumulation of proliferating cells expressing the neuronal marker NeuroD. These data show that post-hypoxic neurogenesis can occur during development.


[Genetic alterations in gallbladder carcinoma: a review].
Earlier evidence suggests that gallbladder carcinoma (GBC) has three carcinogenic pathways; de novo development; adenoma-carcinoma sequence; and hyperplasia-carcinoma sequence associated with an anomalous arrangement of the pancreaticobiliary duct (AAPBD). We review gene abnormalities in GBC reported to date. p53 mutation and its protein overexpression are frequently observed in de novo carcinoma and GBC with AAPBD, but never found in carcinoma with adenoma. The incidence of K-ras codon 12 mutation in GBCs with AAPBD is significantly higher than that in the other types. Mutation of K-ras is never detected in carcinoma with adenoma. These findings suggest that diverse genetic pathways may exist in gallbladder carcinogenesis and reflect morphologic variations.


[Astragalus injection ameliorates cisplatin-induced nephrotoxicity in mice].
To examine the protective effects of Astragalus injection (AI) on cisplatin (DDP)-induced nephrotoxicity and to explore the mechanism of its nephroprotection. The S180-bearing model was established, and fifty mice were randomly divided into five groups: control mice, DDP-injected mice (3.5 mg x kg(-1)) and AI-pretreated mice (12, 8, 4 g x kg(-1)). Tumor inhibition rate, renal functions, histological findings were investigated. The apoptotic cells were counted by TUNEL and the presence of Bax, Bcl-2 in renal tissues was determined by immunohistochemistry. Administration of DDP or DDP plus AI showed promising anti-tumor activities as compared with control group. Interestingly, a combination of DDP and AI (12, 8 g x kg(-1)) led to enhanced tumor growth inhibition as compared with DDP alone (all P < 0.05). Compared with that from control, the number of TUNEL-positive cells and the Bax/Bcl-2 ratio was increased significantly in the kidneys of DDP treated mice (P < 0.05). High-dose AI pretreatment significantly reduced the elevated number of TUNEL-positive cells and the Bax/Bcl-2 ratio (P < 0.05), and it showed a superior nephroprotective effect than any other dose. AI significantly also decreased both the damage to renal function and histological pathology. Pre-treatment with AI attenuates cisplatin-induced nephrotoxicity without compromising the anti-tumor efficacy of DDP, which might be involved in regulating the Bax and Bcl-2 expression.


Transcranial magnetic stimulation: applications for neuropsychopharmacology.
Transcranial magnetic stimulation (TMS) provides new possibilities for studying localized changes in the electrical properties of the human cortex. TMS combined with electromyography (EMG) has revealed that drugs blocking Na(+) or Ca(2+) channels such as phenytoin, lamotrigin or carbamazepine change the motor threshold without affecting intracortical inhibition or facilitation. Gabaergic agents vigabatrin, lorazepam, diazepam, baclofen and ethanol do not affect the motor threshold, but increase intracortical inhibition and decrease facilitation. N-methyl-D-aspartate receptor antagonists riluzole, dextromethorphan and memantine have similar effects. Dopamine receptor antagonists such as haloperidol, but not sulpiride, decrease intracortical inhibition and increase intracortical facilitation. Other monoamines, such as serotonin and noradrenaline, may have some modulating effect on the cortical excitability. However, TMS combined with EMG gives only indirect evidence about the excitability of the motor cortex because spinal mechanisms may contribute to the results. Cortical excitability can be studied directly by combining TMS with brain imaging methods such as electroencephalography (EEG). Motor and non-motor areas can be stimulated and subsequent brain activity can be measured. Ethanol has been shown to modulate EEG responses evoked by motor-cortex TMS, the effects being largest at the right prefrontal cortex, meaning that ethanol would have changed the functional connectivity. Furthermore, alcohol decreases amplitudes of EEG responses after the left prefrontal stimulation mainly in anterior parts of the cortex, which may be associated with the decrease of the prefrontal cortical excitability. Taken together, TMS provides a new insight to the actions of central nervous system drugs at the cortical level.


A new scale insect of the extinct family Weitschatidae (Insecta: Hemiptera: Coccomorpha) from mid-Cretaceous Burmese amber.
A new genus and species of the extinct family Weitschatidae, Criniverticillus longicumulus gen. et sp. nov. (Hemiptera: Coccomorpha), is described and illustrated from mid-Cretaceous Burmese amber. The new species is based on a fossil specimen with complete body, wings and antennae. The family diagnosis is updated to include similarities between Criniverticillus, Pseudoweitschatus and Weitschatus. An identification key to species of Weitschatidae is provided.


Bit error rate improvement by nonlinear optical decision element.
We present a novel approach to the improvement of the bit error rate (BER) in optical communications. We propose a design of advanced optical receiver enhanced by a nonlinear all-optical decision element. As a particular example, we demonstrate a substantial improvement in the BER over the conventional receiver for operation at 40 Gbits/s.


Histiocytosis X mimicking recurrent malignant disease: a report of two cases.
Two cases of histiocytosis X initially thought to be recurrent malignant disease are described. Previously reported cases associated with malignant disease are reviewed and the importance of biopsy confirmation of recurrence is emphasised.


Coupling digestion in a pilot-scale UASB reactor and electrochemical oxidation over BDD anode to treat diluted cheese whey.
The efficiency of the anaerobic treatment of cheese whey (CW) at mesophilic conditions was investigated. In addition, the applicability of electrochemical oxidation as an advanced post-treatment for the complete removal of chemical oxygen demand (COD) from the anaerobically treated cheese whey was evaluated. The diluted cheese whey, having a pH of 6.5 and a total COD of 6 g/L, was first treated in a 600-L, pilot-scale up-flow anaerobic sludge blanket (UASB) reactor. The UASB process, which was operated for 87 days at mesophilic conditions (32 ± 2 °C) at a hydraulic retention time (HRT) of 3 days, led to a COD removal efficiency between 66 and 97 %, while the particulate matter of the wastewater was effectively removed by entrapment in the sludge blanket of the reactor. When the anaerobic reactor effluent was post-treated over a boron-doped diamond (BDD) anode at 9 and 18 A and in the presence of NaCl as the supporting electrolyte, complete removal of COD was attained after 3-4 h of reaction. During electrochemical experiments, three groups of organochlorinated compounds, namely trihalomethanes (THMs), haloacetonitriles (HANs), and haloketons (HKs), as well as 1,2-dichloroethane (DCA) and chloropicrin were identified as by-products of the process; these, alongside free chlorine, are thought to increase the matrix ecotoxicity to Artemia salina.


Work and neck pain: a prospective study of psychological, social, and mechanical risk factors.
To determine the impact of occupational psychological/social and mechanical factors on neck pain, a prospective cohort study with a follow-up period of 2 years was conducted with a sample of Norwegian employees. The following designs were tested: (i) cross-sectional analyses at baseline (n=4569) and follow-up (n=4122), (ii) prospective analyses with baseline predictors, (iii) prospective analyses with average exposure over time [(T1+T2)/2] as predictor, and (iv) prospective analyses with measures of change in exposure from T1 to T2 as predictors. A total of 2419 employees responded to both the baseline and follow-up questionnaire. Data were analyzed using ordinal logistic regression. After adjustment for age, sex, neck pain at T1, and other exposure factors that had been estimated to be confounders, the most consistent risk factors were role conflict (highest OR 2.97, 99% CI: 1.29-6.74) and working with arms raised to or above shoulder level (highest OR 1.37, 99% CI: 1.05-1.78). The most consistent protective factors were empowering leadership (lowest OR 0.53, 99% CI: 0.35-0.81) and decision control (lowest OR 0.60, 99% CI: 0.36-1.00). Hence, psychological and social factors are important precursors of neck pain, along with mechanical factors. Although traditional factors such as quantitative demands and decision control play a part in the etiology of neck pain at work, in this study several new factors emerged as more important.


Effect of suckling an isotonic solution of sodium acetate, sodium bicarbonate, or sodium chloride on abomasal emptying rate and luminal pH in calves.
To compare abomasal emptying rates in calves after suckling milk replacer or 3 common orally administered electrolyte solution components. 5 male calves < 35 days of age. Calves with a cannula fitted in the abomasal body were fed 2 L of milk replacer with or without parenteral administration of atropine (0.01 mg/kg, i.v., then 0.02 mg/ kg, s.c., q 30 min) or isotonic (150 mM) solutions of sodium acetate, NaHCO(3), or NaCl in a randomized crossover design. Abomasal emptying rates were determined via scintigraphy, acetaminophen absorption, ultrasonography, and change in abomasal luminal pH. Scintigraphic half-emptying time, time of maximal plasma acetaminophen concentration, ultrasonographic half-emptying time, and pH return time indicated similar abomasal emptying rates following suckling of isotonic sodium acetate, NaHCO(3), and NaCl solutions, whereas the emptying rate of milk replacer was significantly slower. Mean maximal abomasal luminal pH was highest following suckling of NaHCO(3) (pH(max)=7.85) and lowest following suckling of NaCl (pH(max)=4.52); sodium acetate (pH(max)=6.59) and milk replacer (pH(max)=5.84) yielded intermediate pH values. Isotonic solutions of sodium acetate, NaHCO(3), and NaCl were rapidly emptied from the abomasum but varied markedly in their ability to alkalinize the abomasum. Sodium bicarbonate-containing orally administered electrolyte solution might increase the frequency of infection or severity of clinical disease in diarrheic calves treated for dehydration by causing prolonged abomasal alkalinization.


Excessive TLR9 signaling contributes to the pathogenesis of spontaneous abortion through impairment of Treg cell survival by activation of Caspase 8/3.
The pregnant uterine microenvironment is repleted with Toll-like receptors (TLRs), however, their roles of these receptors in establishing tolerance to growing fetus are largely unknown. Decidual TLR1, TLR3, TLR4, TLR8 and TLR9 gene expressions were significantly over-expressed in patients of spontaneous abortion compared with elective abortion with normal pregnancy. In particular, the expression of TLR4 and TLR9 mRNA was considerably higher than that of remaining TLRs. We mimic TLR9 signal with combination of its pathogenic ligand CpG ODN and antagonists ODN in a well-established abortion-prone CBA/J×DBA/2 model. CpG ODN dramatically boosted fetal loss and lowered the proportion of Regulatory cells (Treg cells) in vivo. CpG ODN directly triggered the impaired survival and increased activity of Caspase 8/3 of Treg cells in vitro. These effects were blocked by antagonist ODN. Excessive TLR9 signaling contributed to maternal-fetal tolerance disruption via an effect on Treg cell survival by activation of Caspase 8/3.


[On the polymorphism of barbiturates in powders and tablets. Part 1: Crystal optical studies on, and melting behaviour of barbital (author's transl)].
Crystal optical studies showed that barbital brands that conform to the standards of the DAB 7--DDR and the Ph. Hung. VI, respectively, present two different crystalline forms. After recrystallization form water or acetone-water mixture (1:1), the optical crystal picture of the brand conforming to the DAB 7--DDR prevails. The melting points of the commercial products do not differ from each other; both substances melt at 187.5 degrees C, whereas the melting points of the recrystallized products are 1.5 degrees and 2 degrees C, respectively, lower.


Correlation between skin tests, inhalation tests and specific IgE in a study of 120 subjects allergic to house dust and Dermatophagoïdes pteronyssinus.
The radioallergosorbent test was compared with currently accepted allergy diagnostic techniques in seventy-four controls and 120 patients with a clinical history of allergy to house dust and Dermatophagoïdes pteronyssinus. The results obtained with D. pteronyssinus allergen extract show a close correlation between the size of the cutaneous reactions and the serum level of allegen-specific IgE. On the other hand, highly positive skin tests to house dust were not always correlated with a positive RAST response for house dust. Similar results were found with inhalation tests. When a purified D. pteronyssinus extract was used, a stronger relationship was observed between RAST, cutaneous and inhalation tests. It can be assumed that RAST for house dust is not of value in patients with house dust and mite allergy. Our findings indicate that the correlations between RAST results and other in vivo test results depend on the purity of the allergen extracts and the selection of patients.


Personal digital assistant with a barcode reader--a medical decision support system for nurses in home care.
Inappropriate medication among elderly people increases the risk of adverse drug-drug interactions, drug-related falls and hospital admissions. In order to prevent these effects it is necessary to obtain a profile of the patients' medication. A personal digital assistant (PDA) can be used as a medical decision support system (MDSS) to obtain a profile of the patients' medication and to check for inappropriate drugs and drug combinations, and to reduce medication errors. The aim of the present study was to evaluate nurses' experiences of using a MDSS in a PDA with a barcode reader, in order to obtain profiles of the patients' medication, regarding drug-drug interactions, therapeutic duplications, and warnings for drugs unsuitable for elderly in home care. The LIFe-reader is a MDSS in a PDA with a barcode reader. By scanning the drug packages in the patients' home, the LIFe-reader obtained profiles of the patients' medication and checked for drug-drug interactions, therapeutic duplications and warnings for drugs unsuitable for elderly people. The LIFe-reader also contained, e.g. drug information and medical reference works. Nurses (n=15) used the LIFe-reader for five weeks during their nursing home care practice assignment. The nurses answered questionnaires about the content and functions of the LIFe-reader before, during and after the nursing home care practice assignment, and were interviewed in focus groups. Descriptive statistics were used and content analysis was applied for qualitative data. By using the LIFe-reader, the majority of the nurses found it easy to obtain profiles of the patients' medication and check for drug-drug interactions, therapeutic duplications and warnings for drugs unsuitable for elderly people. Most nurses regarded the LIFe-reader to reduce drug-related risks of falling, and some thought it could reduce the drug-related admissions to hospitals. The scanning function was described as easy and time saving, although not always possible to use. The LIFe-reader was regarded as a useful and user-friendly MDSS, but more content and functions were requested. We found that the LIFe-reader has the potential to be a useful and user-friendly MDSS for nurses in home care when obtaining profiles of the patients' medication regarding drug-drug interactions, therapeutic duplications and warnings for drugs unsuitable for elderly. A regular scanning of the patients' drugs in their home might support nurses and general practitioners (GPs) in reducing the inappropriate use of drugs. If the LIFe-reader should be used in a larger scale among nurses, more content and functions are necessary.


[MR tomography of the liver at 1.5 tesla. The value of T1-weighted imaging with a fast multislice gradient-echo sequence during respiratory standstill].
The diagnostic value of a fast multislice gradient-echo sequence was compared with that of conventional spin-echo sequences in a prospective study of 76 patients. With the multislice gradient-echo sequence, the entire liver can be examined in less than 3 minutes since five sections can be imaged during one breath-holding period. The strongly T1-weighted gradient-echo sequence (GRE 100/5/80 degrees) yields a significantly better T1-contrast than the T1-weighted spin-echo sequence (SE 500/15) (p less than 0.01) and thus improves the visualization of liver lesions. Another major advantage of the fast gradient-echo sequence is the pronounced reduction of motion artefacts.


Parental perspectives on the diagnostic process for Duchenne and Becker muscular dystrophy.
Duchenne and Becker muscular dystrophy (DBMD) are allelic, X-linked recessive, neuromuscular disorders characterized by progressive loss of muscle function. Despite technological advances in diagnostic genetic testing, the mean age at diagnosis (4.7 years) has remained unchanged for decades. The purpose of the study was to characterize parental perceptions of the diagnostic process and identify factors that influence the timeline. Data collection for this qualitative study consisted of six individual and five group interviews. Participants (N = 30) included Hispanic, non-Hispanic black, and non-Hispanic white parents whose son was diagnosed with DBMD. The "help-seeking behavior model" provided an analytical framework to analyze the data. Parents did not move through help-seeking stages unidirectionally as described in other studies. Delays existed at each stage. We identified personal, familial, social, cultural, and provider factors that impeded earlier diagnosis. These barriers prolonged movement through a stage or led families to repeat previous stages. Results should initiate debate among system administrators, patient advocates, and healthcare providers regarding which barriers may be most modifiable and which interventions may reduce the time to diagnosis and limit parental emotional distress.


Dislocation density-dependent photorefractive effect in (001)-cut GaAs.
We present studies of the photorefractive effect in nonphotorefractive orientations of liquid-encapsulated Czochralski-grown GaAs crystals. Picosecond diffraction experiments conducted in different samples show that a forbidden photorefractive signal correlates well with dislocation density, which points out that the effect arises from strain fields and growth defects.


[Caution and compassion in nursing care].
Caution and compassion are two terms which evoke the ambivalence of the care relationship, the proper distance to maintain, the empathy to put in place, the trust. It is also important for health professionals not to let themselves be overwhelmed by patients, who may themselves be overwhelmed by their disease.


Pediatric pseudotumor cerebri.
Although PTC most frequently occurs in obese females of childbearing age, the syndrome occurs in children as well.(3),(5) Prepubertal children with PTC have a lower incidence of obesity compared with adults and there is no sex predilection. The onset of puberty is best defined by the onset of secondary sexual characteristics such has menarche, pubic hair, and breast development. Children with PTC have a higher incidence of associated conditions and cranial nerve deficits compared with adults. Similar to adult patients, children are at risk for the development of permanent visual loss. In rare instances, children initially diagnosed with PTC will be found to harbor an intracranial neoplasm such as gliomatosis cerebri. An intracranial pressure of 28 cm H2O has recently been established as the upper limit of normal in children.31 Treatment is indicated for the symptomatic management of headaches and to preserve vision. Most children respond to medications such as acetazolamide, furosemide, or topiramate. Surgical treatment such as ONSF and shunting procedures are indicated for children with severe headaches, visual loss, or both despite maximal tolerated medical treatment.


Effects of alpha-mangostin from mangosteen pericarp extract and imidacloprid on Nilaparvata lugens (Stal.) and non-target organisms: toxicity and detoxification mechanism.
The brown planthopper, Nilaparvato lugens Stat. (BPH) is the most devastating insect pest in rice fields. Outbreaks of BPH, which are resistant to many synthetic insecticides, can cause total rice crop loss. This research was done to evaluate the efficiency of extracts of mangosteen pericarp (Garcina mangostana L.) as an alternative control of BPH Thailand strain. Topical spraying was applied to various stages of nymphal and adult BPH to determine toxicity. An ethanol extract of mangosteen pericarp extract gave the best control of BPH, with LC50 of 4.5% w/v (r2 = 0.95) with 3rd instar BPH nymphs when compared with the other solvents, hexane, acetone and dichloromethane. The active compound, alpha-mangostin showed an LC50 of 5.44%w/v (r2 = 0.88). The toxicity of this extract was less than that of Imidacloprid which showed an LC50 of 0.0042% w/v (r2 = 0.99). The toxicity to non-target organisms was determined. This extract showed toxicity to guppies ((LC50 = 2.53 and 4.27 ppm for females and males, respectively; r2 = 0.97 and 0.97, respectively), bees (LC50 = 4.38% w/v, r2 = 0.95) and mice (no oral acute toxicity and no dermal inflammation but showed eye irritation in 1 day which became normal within 3 days). In vitro detoxification enzyme activities of carboxylesterase, acetylcholinesterase and glutathione-s-transferase from BPH after 24 hours exposure were also observed. Carboxylesterase showed stronger activity than other enzymes. Toxicity in terms of LC50 values of both the extract and imidacloprid treatments increased in each generation. The LC50 values for each generation were 4.22-6.67 after sequential spraying. After the ethanol extract was kept at 4 degrees C, room temperature and 55 degrees C for 3 months, the quantity of alpha-mangostin and the BPH control efficiency was lower at 55 degrees C than those for other temperatures. The results from this research indicate that mangosteen pericarp extract can be an alternative insecticide for the control of BPH, which may possess high efficiency, cause with fewer environmental problems and result in less resistance in the BPH.


Persistent median artery (palmar type) and median nerve block in the forearm: observational study of prevalence.
We sought to define the crude prevalence rate of the persistent median artery (PMA) (palmar type). Although there is no reported case in the anesthetic literature, a few sporadic case reports and series reported in anatomical and orthopedic journals describe an incidence of between 1.5% and 27.1%. We conducted a prospective observational study to define the crude prevalence of the PMA (palmar type) by scanning 100 forearms of 50 volunteers using a high-frequency ultrasound probe. We found 19 PMAs in 13 individuals, thus giving a prevalence of 19%. Other arterial variants were also identified within this population. Anatomical variations of the blood supply to the forearm and hand can be identified with available high-frequency ultrasound equipment. Arterial variants immediately adjacent to the median nerve may occur in approximately 1 in 5 limbs. Practitioners should actively seek their presence or absence.


Effects of caloric supplementation on growth in children with uremia.
Growth and nutritional status were evaluated in 12 children with chronic renal insufficiency over a 2-year period. During 1 year the children received nutritional counseling but no caloric supplement; during year 2, they received both nutritional counseling and caloric supplementation. With caloric supplementation, food intake as a percent of normal increased from 73 to 103% and the rate of growth increased from 59 to 90% of expected. The deviation from normal for height, as measured by SD scores, did not improve during the period of supplementation, that is, there was no accelerated or compensatory growth. During the unsupplemented period growth rate, as percent normal, correlated with energy intake as percent normal (r = 0.68). Growth rate and energy intake did not correlate during the period of caloric supplementation. Anthropometric measurements and plasma albumin increased during the period of supplementation, but other indices of body protein mass did not change. Plasma lipid levels also rose with caloric supplementation. We interpret these findings as evidence that dietary energy deficiency exists in many children with chronic renal insufficiency and contributes to their poor growth. Caloric supplementation in children improves total energy intake, growth rate, and skinfold thickness, but it does not lead to accelerated or compensatory growth.


Big data to smart data in Alzheimer's disease: Real-world examples of advanced modeling and simulation.
Many disease-modifying clinical development programs in Alzheimer's disease (AD) have failed to date, and development of new and advanced preclinical models that generate actionable knowledge is desperately needed. This review reports on computer-based modeling and simulation approach as a powerful tool in AD research. Statistical data-analysis techniques can identify associations between certain data and phenotypes, such as diagnosis or disease progression. Other approaches integrate domain expertise in a formalized mathematical way to understand how specific components of pathology integrate into complex brain networks. Private-public partnerships focused on data sharing, causal inference and pathway-based analysis, crowdsourcing, and mechanism-based quantitative systems modeling represent successful real-world modeling examples with substantial impact on CNS diseases. Similar to other disease indications, successful real-world examples of advanced simulation can generate actionable support of drug discovery and development in AD, illustrating the value that can be generated for different stakeholders.


Xanthogranulomatous gastritis mimicking malignant GIST on F-18 FDG PET.
Xanthogranulomatous gastritis (XGG) is a rare inflammatory lesion of the stomach, with only 11 reported cases worldwide. Furthermore, reports on the use of detailed diagnostic imaging in XGG are not available. Herein, we describe a case of XGG with detailed diagnostic imaging mimicking malignant gastrointestinal stromal tumor (GIST) in light of the current literature. A 79-year-old woman who presented with epigastric pain was referred to our hospital. Upper gastrointestinal endoscopy revealed an elevated lesion similar to a submucosal tumor (SMT). F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showed intense FDG uptake in the mass. Additional imaging studies revealed a malignant GIST, which was suspected of having infiltrated the left lobe of the liver. Open surgery was carried out, but tumorous lesions were not found. For exact histopathological diagnosis, partial resection of the thickening gastric wall was performed, and XGG was diagnosed. We conclude that benign conditions, including XGG, should be considered when intense FDG uptake in SMT is found.


[Effect of post-treatment with dry extract from vicia truncatula on NADPH-GSH dependent system of rat liver during chronic alcohol intoxication].
Experiments on white female rats showed that chronic ethanol consumption leads to activation of the NADPH - GSH dependent system of the liver, which provides protection against ethanol-induced oxidative stress. Post-treatment administration of dry extract from Vicia truncatula Fish ex Bieb. (300 mg/kg body weight) on the background of 40% ethanol increased this adaptive reaction without depletion in the system, in contrast to what was observed in rats treated with carsil. These results suggest a significant hepatoprotective effect of the dry extract during the chronic alcohol-induced injury of the liver.


[The Kibbutz physician: family medicine theory in practice].
124 of 251 physicians living and working in 109 of the 194 kibbutzim in Israel answered a 125-item postal questionnaire on their professional and personal characteristics and the special issues affecting a kibbutz physician. Most were specialists in family practice, had had the best of modern medical training, were deeply involved in their communities, and were familiar with all aspects of their patients' lives. They were given the opportunity to express the bio-psycho-social model of family medicine. This study relates to the special encounter of family medicine theory and its practice in the kibbutz system of health care delivery, including the problems of the kibbutz physician and the degree of personal satisfaction derived.


Effects of initial dose on eastern equine encephalomyelitis virus dependent mortality in intrathoracically inoculated Culiseta melanura (Diptera: Culicidae).
Viral growth characteristics that favor rapid and prodigious virion production may increase virus transmission but be detrimental to infected hosts. Several arboviruses, including eastern equine encephalomyelitis (EEE) virus, negatively affect the survival of their infected mosquito vectors. To test the hypothesis that the mosquito virulent properties of EEE virus are caused by the presence of intrinsic viral growth properties, we investigated the effects of infecting dose on the survival of intrathoracically inoculated Culiseta melanura (Coquillett). Daily survival of age-matched females inoculated with either a low initial dose of 10(1.5) plaque-forming units (PFUs) per mosquito or a high initial dose of 10(5.5) PFUs per mosquito was monitored for 8 wk. Compared with diluent inoculated controls, mosquitoes from both dosage groups displayed highly significant decreases in survival. No significant differences in daily survival were detected between the two infected groups. Virus production within inoculated mosquitoes was assessed by sampling mosquitoes every 12 h for 96 h after inoculation. Rapid virus amplification occurred in both dosage groups, and by 24 h after exposure the mean viral loads in mosquitoes inoculated with the low dose were comparable to those inoculated with the high dose. Likewise, although detectable virions appeared sooner in the saliva of high dosage mosquitoes, by 72 h after inoculation no significant differences in virus transmission were detected between the two exposure groups. These results indicate that the virulence of EEE virus for its enzootic North American mosquito vector is not dosage dependent and likely reflects the inherent growth properties of this virus within infected mosquitoes.


Update on the management of Lennox-Gastaut syndrome.
Lennox-Gastaut syndrome is a severe childhood epilepsy disorder characterized by encephalopathy and multiple, often intractable, seizure types. The drop attack is the most frequently recognizable seizure type in this patient population, and is also the most dangerous physically, thus severely limiting quality of life. The diagnosis is confirmed by electroencephalography, for which the classic pattern is a slow 2.5 Hz generalized spike-and-wave. Newer pharmacologic treatments include rufinimide and clobazam. However, antiepileptic drugs are often exhausted in pursuit of seizure control requiring nonpharmacologic interventions. These include dietary therapies, vagus nerve stimulation, and epilepsy surgery, including corpus callosotomy and focal curative resection. Although large lobar resections are often required, very localized, discrete resections may be possible, as in symptomatic Lennox-Gastaut syndrome (specifically, hypothalamic hamartoma). We review the history of the disease and current management options.


Ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction.
A recent study suggests that exogenous ghrelin administration might decrease renal sympathetic nerve activity in conscious rabbits. In the present study, we investigated whether ghrelin administration would attenuate left ventricular (LV) remodeling following myocardial infarction (MI) via the suppression of cardiac sympathetic activity. Ghrelin (100 microg/kg sc, twice daily, n = 15) or saline (n = 15) were administered for 2 wk from the day after MI operation in Sprague-Dawley rats. The effects of ghrelin on cardiac remodeling were evaluated by echocardiographic, hemodynamic, histopathological, and gene analysis. In addition, before and after ghrelin (100 microg/kg sc, n = 6) was administered in conscious rats with MI, the autonomic nervous function was investigated by power spectral analysis obtained by a telemetry system. In ghrelin-treated rats, LV enlargement induced by MI was significantly attenuated compared with saline-treated rats. In addition, there was a substantial decrease in LV end-diastolic pressure and increases in the peak rate of the rise and fall of LV pressure in ghrelin-treated MI rats compared with saline-treated MI rats. Furthermore, ghrelin attenuated an increase in morphometrical collagen volume fraction in the noninfarct region, which was accompanied by the suppression of collagen I and III mRNA levels. Importantly, a 2-wk administration of ghrelin dramatically suppressed the MI-induced increase in heart rate and plasma norepinephrine concentration to the similar levels as in sham-operated controls. Moreover, acute administration of ghrelin to MI rats decreased the ratio of the low-to-high frequency spectra of heart rate variability (P < 0.01). In conclusion, these data suggest the potential usefulness of ghrelin as a new cardioprotective hormone early after MI.


Tracks as frames of reference for academic self-concept.
This study compared the development of academic self-concepts between different educational programs. A longitudinal cohort study in Flanders (3205 students in 46 schools) was used to compare students' academic self-concepts during the first three years of secondary education. General academic self-concept, self-concept in mathematics and self-concept in Dutch were measured. The investigated educational programs, called tracks, differ in the extent they are academically or vocationally focused and differ in average student academic ability. To control for selection effects, students who are comparable across the four tracks were matched using propensity score matching, Mahalanobis distance matching and coarsened exact matching. By means of multiple indicator quadratic latent growth curves, pairs of tracks that are hierarchically consecutive were compared regarding the development in academic self-concepts. For the two highest tracks, it was beneficial to be allocated to the highest track, whereas the pairwise comparisons between the three lower tracks indicated a detrimental effect of being in a higher track. The findings from this study do not support the big-fish-little-pond hypothesis or the basking in reflected glory hypothesis. Differences between tracks for the development of self-concepts only became apparent after two years.


5'-derivatives of oligonucleotides as primers of DNA polymerization catalyzed by AMV reverse transcriptase and Klenow fragment of DNA polymerase 1.
The Km and Vmax values for d(pT)8 and its derivatives containing various 5'-end groups were estimated in the reaction of polymerization catalyzed with AMV-RT and FK. The change in affinity of modified primers was more pronounced in the case of AMV-RT than in the case of FK. Introducing in d(pT)8 of intercalators such as phenazinium, ethidium and daunomycin residues results in 2.7-, 8.7- and 11-fold increases in the primer affinity to AMV-RT, respectively. However, in the case of hemin and cholesterol derivatives the Km values were 3 and 5 times higher than those for d(pT)8. Compared to d(pT)8, the affinity of FK to all the above analogs was 2.3-3.6 times higher with the exception of cholesterol derivative to which it was 2.4-fold lower. The effect of the 5'-end residues on the Vmax values of d(pT)8 was small and ranged from 44% to 120% of that for d(pT)8. Therefore such reactive derivatives of oligonucleotides can be used as effective primers of AMV-RT and FK. Possible reasons for various effects of the 5'-end residues of the primer on its interaction with FK or AMV-RT in the presence of poly(A) are discussed.


Recent trends in clothing physiology.
The need for high-performance protective clothing systems in space, polar, and underwater operations and in industrial environments has stimulated research in clothing physiology. New, sophisticated measurement methods, some of which are going to be international standards, have facilitated this research. Measurements with subjects have validated manikin data, but have also provided information about the dynamic character and the individual variability of thermal properties of clothing under conditions encountered in the field. Manikin measurements of the basic thermal properties of clothing (insulation and evaporative resistance) have to be corrected to apply to the user situation, due to the effects of wind, posture, body movement, and moisture absorption. Evaporative heat transfer is better defined and should be incorporated in heat exchange models and thermal indices. Important aspects of clothing physiology remain to be investigated.


Screening of cytotoxic activities of Strychnos alkaloids (methods and results).
The potential cytotoxic activities of 46 alkaloids isolated from different Strychnos species were tested on different cancer or normal cells cultured in vitro. The authors used a relatively simple microtest which gives good reproducibility. Most of the active compounds belong to the usambarane skeleton but other structure-activity relationships are being discussed.


Does EuroSCORE work in individual European countries?
Because of national epidemiological differences in adult heart surgery in Europe, the effectiveness and desirability of a pan-European score for the assessment of quality of surgical care remains controversial. We assessed the predictive value of EuroSCORE in national subsets of the EuroSCORE database. The EuroSCORE development data set was divided into national subsets of which those with 500 or more patients were selected for analysis. The Hosmer-Lemeshow goodness-of-fit test was applied to assess the calibration of the EuroSCORE model on individual national samples and the areas under the receiver operating characteristic (ROC) curve were measured to analyse the EuroSCORE discriminative power on individual death prediction. There were 18676 patients in the six largest national samples: Germany, United Kingdom, Spain, Finland, France and Italy (mean: 3113 patients; range: Finland 1266 to France 4507). Major differences were observed in national distribution of procedures: coronary artery bypass grafting accounted for 77.7% of procedures in Finland but only 46.2% in Spain. The EuroSCORE model goodness-of-fit was satisfactory in all countries (P-value overall: 0.4; UK: 0.34; Finland: 0.87; no values less than 0.05). Areas under ROC curves were 0.81 in Germany, 0.79 in the UK, 0.74 in Spain, 0.87 in Finland, 0.82 in France and 0.82 in Italy. Despite epidemiological differences between European countries, the discriminative power of EuroSCORE was good in Spain and excellent in all other countries. The system, developed from a merged European database, can therefore be used to assess improvement in quality of care achieved by surgeons and institutions as well as for international European comparison in adult heart surgery.


[Long-term results after surgical repair for aged atrial septal defect].
Between 1980 and 1992, 84 patients over 30 years were underwent operative closure of atrial septal defect (ASD). Preoperative complaints and lower cardiac function were more frequent in the older than in the younger, but the clinical symptom of both generation improved significantly after surgery. Only a 67-year-old patient died after surgery due to low cardiac output syndrome. No long-term death occurred. The incidence of atrial fibrillation was increased postoperatively compared with preoperatively. Therefore, we recommend early surgical repair for aged ASD before thirties, if possible.


Establishment of spontaneously immortalized rat type 1 astroglial cell lines: the role of p53 in astroglial carcinogenesis.
We established five spontaneously immortalized cell lines using purified rat type 1 astroglia on a rigid transfer schedule. All the cell lines maintained their polygonal shape, regular pavement growth, low saturation density, positive glial fibrillary acidic protein expression, and serum requirements, while none were tumorigenic in nude mice. We then obtained a spontaneously transformed cell line by maintaining the cells for 6 months at a high cell density. Since alterations of the tumor suppressor p53 gene have been reported in the immortalization of some cell lines and in transformation of others, we characterized p53 in immortalized, spontaneously transformed, and 5 Nethyl-N-nitrosourea (ENU)-transformed cell lines. While each of the ENU-induced or the spontaneously transformed cell lines exhibited p53 gene mutations that resulted in amino acid alterations, no alterations in the p53 gene were observed in any of the immortalized cell lines. Thus, alterations of the p53 protein correlate more strongly with transformation than with immortalization of type 1 astroglia. Immortalization may be regulated by gene(s) other than p53. Spontaneously immortalized type 1 astroglial cell lines may provide a new tool to investigate an initial step of astroglial carcinogenesis.


Trends in the proportions of stroke subtypes and coronary heart disease in the Japanese men and women from 1995 to 2009.
The limited evidence on trends in the proportions of stroke subtypes and coronary heart disease in Japan. Stroke and coronary heart disease registrations from three periods including 1995 to 1999, 2000 to 2004, and 2005 to 2009 were examined for residents aged 55-74 years for each period who were admitted with acute cardiovascular disease. Subjects who experienced an onset of stroke, or coronary heart disease, or moved at the beginning of each period were excluded. There were 3181 cases of strokes and 768 cases of coronary heart disease in 1995-2009. The age-adjusted proportion of intraparenchymal hemorrhage was 34%, 25%, and 24% (p = 0.02) for men, and 27%, 29%, and 30% (p = 0.41) for women; ischemic stroke was 57%, 68%, and 73% (p = 0.002) for men, and 46%, 52%, and 58% (p = 0.02) for women; and embolic infarction was 23%, 31%, and 32% (p < 0.001) for men, and 21%, 23%, and 30% (p = 0.009) for women, respectively. The proportions of sudden cardiac death and myocardial infarction among total coronary heart disease did not change during the three periods for either sex. Between 1995-1999 and 2005-2009, the proportion of intraparenchymal hemorrhage among all types of stroke decreased for men, while the proportions of ischemic stroke among all types of stroke and embolic infarction among ischemic stroke increased for both men and women.


Modeling momentum in gradual demographic transitions.
The analysis of population momentum following a gradual decline in fertility to replacement level provides valuable insights into prospects for future population growth. Here, we extend recent work in the area by applying a new form of the quadratic hyperstable (QH) model, which relates exponentially changing fertility to the resultant exponentiated quadratic birth sequence. Modeling gradual transitions from an initial stable population to an ultimate stationary population indicates that such declines in fertility increase momentum by a product of two factors. The first factor is a previously noted continuation of stable growth for half the period of decline. The second is a not previously appreciated offsetting factor that reflects the interaction between the decline in fertility, the changing age pattern of fertility, and the changing age composition of the population. Numerical examples using both hypothetical and actual populations demonstrate that for declines of any length, the product of the two factors yields momentum values that closely agree with the results of population projections. The QH model can examine monotonic transitions between any two sets of constant vital rates. As a generalization of the fixed-rate stable model, it has great potential value in numerous areas of demographic analysis.


The effect of ankle brace type on braking response time-A randomised study.
The question whether or not a patient with an ankle brace should drive a car is of obvious importance because brake response time (BRT) is considered one of the most important factors for driving safety. Applying a crossover study design, 70 healthy participants (35 women, 35 men) participated in our study. BRT was assessed using a custom-made driving simulator. We assessed BRT under six conditions: without a brace (control) (1), with a typical postoperative ankle brace with adjustable ROM and the settings: unrestricted (2), fixed at 15° (3) plantar flexion, restricted with 15°/50° (4) (dorsal/plantar flexion), a brace for ligament instabilities (5) and an elastic ankle bandage (6). Participants were instructed to apply the brake pedal exclusively with the right foot as quickly as possible on receipt of a visual stimulus. The 70 participants showed significantly impaired BRT with the ankle brace for ROM restriction in the settings: unrestricted (p<0.001), fixed at 15° plantar flexion (p<0.001) and 15°/50° dorsal/plantar flexion (p<0.001) as compared to the control group. BRT was not impaired with the brace for ankle instabilities or the elastic ankle bandage. In conclusion, right-sided ROM restricting ankle braces involve significant impairment of BRT in healthy participants. No such prolonged BRT was found for an elastic ankle bandage or the ligament brace.


Kinematic and dynamic analysis of running under conditions of variable gravity.
A new training system was designed and realised by the engineer G. Scuderi: a centrifugal track for runners. The principal advantage of this track is to increase the forces on athlete during the run with an effect very similar to that of an "artificial gravity", so the athlete can develop more muscle power. A multibody numerical model of a runner was developed to analyse the behaviour of the athlete on the centrifugal track. The multibody model was calibrated by experimental analysis; in fact, the joint angles were measured by a digital image processing system and introduced as input in the numerical simulation. The numerical results obtained are the values of many kinematic and dynamic variables, in particular the ground reaction force and the moments in the hip, knee, and ankle joints. A comparison between the normal running and that on the centrifugal track was carried out, demonstrating the validity of training on the latter. The results of the numerical simulation confirm that the power developed during running on the track, and the corresponding work performed by the joints, is considerably greater than that found during normal running.


Vanadium determination in chloride matrices using ICP-MS: finding the optimum collision/reaction cell parameters for suppressing polyatomic interferences.
Efficiencies of He/NH3 and He/H2 collision gases were compared in a conventional type of hexapole cell of an inductively coupled plasma mass spectrometer (ICP-MS). The optimum conditions [hexapole and quadrupole bias voltage (V(H) and V(Q)) and collision/reaction gas flow rates] were tested for vanadium determination (51V) in chloride matrices. When the He/H2 mixture was used, the optimum values of V(H) and V(Q) were -10.0 and -8.0 V, respectively. This set-up corresponds to the kinetic energy discrimination effect. When the He/NH3 mixture was used, the optimum values of V(H) and V(Q) were +10.0 and -7.0 V, respectively. Positive V(H) values correspond to the ion kinetic energy effect, which allows the reactivity of the ions entering the collision/reaction cell with the reaction gas to be controlled. The obtained results showed that the He/H2 mixture is not optimal for V determination in samples containing chlorides due to the insufficient suppression of the polyatomic interference of 35Cl16O+. Data obtained from vanadium determination using the He/NH3 mixture were consistent for all selected Cl- concentrations, and the results were acceptable. The detection limit was comparable with detection limits obtained from ICP-MS equipped with a dynamic reaction cell. Analyses of elements forming interfering molecules, e.g., iron (56Fe), arsenic (75As) and selenium (80Se), were in good agreement with the certified values for both studied collision/reaction gas mixtures.


The strength-endurance relationship in skeletal muscle: its application to helmet design.
The isometric strength and endurance of the neck muscles in man was measured in four male subjects during dorsal, ventral, and lateral flexion of the head in a helmet dynamometer. The purpose of these experiments was to quantify the maximum strength of the neck muscles in these directions and to examine the relationship between isometric strength and endurance for various submaximal isometric tensions. Isometric contractions were sustained to fatigue by these subjects at tensions of 25, 40, 55, 70, and 90% of the maximum isometric strength in each of the directions of movement. Generally, the endurance of the muscles involved in ventral flexion was less than that found in dorsal and lateral flexion of the head. However, the strength of the muscles involved was progressively greater for lateral, dorsal, and ventral flexion, respectively. The implication of these findings in helmet design and helmet loading are discussed.


Evolving approach to the varicocele.
The varicocele is the most common cause of male infertility world wide. Varicoceles have been found in 15% of the normal male population and in up to 40% of patients with male infertility. In approximately 70% of patients with secondary infertility, a varicocele is an underlying cause. Understanding of the pathophysiology, treatments, and outcomes of a varicocele and varicocele repair has evolved significantly over the past several decades. Our goal is to discuss the approach to its diagnosis and treatment that has evolved.


Ecology of non-O 1 Vibrio cholerae in Toyama Prefecture.
The ecology of non-O 1 Vibrio cholerae and Vibrio mimicus as causes of cholera-like diarrhea or seafood-associated gastroenteritis has been investigated in Toyama Prefecture since 1980. The relationship between biological or serological characteristics of the isolates and their enteropathogenicity is discussed. Overall isolation rates from river water, sea water, and fish were 24.0, 59.5, and 33.7%, respectively, the isolation frequency being, in general, extremely high in the summer season, although the organisms were detected all year around in the case of sea water. Most isolates from river water were unable to grow on plates of TCBS agar to which colistin was added at a concentration of 1 microgram/ml (CL-TCBS). These strains quickly fermented cellobiose. O-51 and O-70 were the two most frequently detected serogroups among them and they did not show enteropathogenicity in the rabbit ileal loop ( RIL ) test. On the other hand, almost all isolates from sea water and fish as well as those from human diarrhea cases were able to grow on CL-TCBS, but were unable to ferment cellobiose quickly. O-36, O-10, O-6, O-8, O-39, and O-26 were the dominant serogroups of these isolates, and some of them showed enteropathogenicity in the RIL test. Six out of 98 isolates from river water, 14 out of 116 from sea water, and 19 out of 112 from fish were classified as Vibrio mimicus . All of these strains were able to grow on CL-TCBS and quickly fermented mannose but not cellobiose. O-41 was the most common serogroup among them and some of these strains showed enteropathogenicity in the RIL test. Production of a cholera-like enterotoxin among the isolates in Toyama Prefecture, if any, seemed to be poor.


Proximal small intestinal microbiota and identification of rod-shaped bacteria associated with childhood celiac disease.
Alterations in the composition of the microbiota in the intestine may promote development of celiac disease (CD). Using scanning electron microscopy (SEM) we previously demonstrated that rod-shaped bacteria were present on the epithelium of proximal small intestine in children with CD but not in controls. In this study we characterize the microbiota of proximal small intestine in children with CD and controls and identify CD-associated rod-shaped bacteria. Proximal small intestine biopsies from 45 children with CD and 18 clinical controls were studied. Bacteria were identified by 16S rDNA sequencing in DNA extracted from biopsies washed with buffer containing dithiothreitol to enrich bacteria adhering to the epithelial lining, by culture-based methods and by SEM and transmission electron microscopy. The normal, mucosa-associated microbiota of proximal small intestine was limited. It was dominated by the genera Streptococcus and Neisseria, and also contained Veillonella, Gemella, Actinomyces, Rothia, and Haemophilus. The proximal small intestine microbiota in biopsies from CD patients collected during 2004-2007 differed only marginally from that of controls, and only one biopsy (4%) had rod-shaped bacteria by SEM (SEM+). In nine frozen SEM+ CD biopsies from the previous study, microbiotas were significantly enriched in Clostridium, Prevotella, and Actinomyces compared with SEM- biopsies. Bacteria of all three genera were isolated from children born during the Swedish CD epidemic. New Clostridium and Prevotella species and Actinomyces graevenitzii were tentatively identified. Rod-shaped bacteria, probably of the indicated species, constituted a significant fraction of the proximal small intestine microbiota in children born during the Swedish CD epidemic and may have been an important risk factor for CD contributing to the fourfold increase in disease incidence in children below 2 years of age during that time.


Cortrak tube placement part 1: confirming by quadrant may be unsafe.
Gastric confirmation by pH is only achievable in approximately 50% of placements and X-rays are expensive and may be misinterpreted. Bedside electromagnetic (EM) guidance offers real-time confirmation. The authors determined the accuracy of guidance in predicting gastric body position from the EM trace using official Cortrak guidance (the EM trace reaches the bottom left quadrant of the anterior screen) compared with local guidance (detailed anterior-depth description of the GI flexures). X-ray, pH or an EM trace beyond the gastric body were used to independently confirm gastric position. Of 496 EM traces, 49% of tubes were in the oesophagus on entry to the lower left quadrant whereas 12% had already reached the gastric body in the upper left quadrant. Overall, predicting position by quadrant was 70% accurate whereas differentiating the pre-gastro-oesophageal junction (pre-GOJ) from the gastric body flexure was 100% accurate. Confirming gastric position by the anterior trace quadrant appears to be unsafe whereas expert differentiation of the pre-GOJ and gastric body flexures was reliable. The authors invite Corpak Medsystems (now owned by Halyard Health) to update its guidance in view of these findings.


TLR4 agonists as immunomodulatory agents.
Monophosphoryl lipid A (MPL) is a potent vaccine adjuvant derived from Salmonella minnesota that was recently licensed in Europe as a component of an improved vaccine for hepatitis B (Fendrix). MPL, like lipopolysaccharide from which it is derived, signals via the TLR4/MD-2 complex. We have produced a series of synthetic Toll-like receptor 4 (TLR4) agonists that are based upon the structure of the major hexa-acylated congener contained within MPL. These TLR4 agonists, termed the aminoalkyl glucosaminide phosphates (AGPs), stimulate the production of various cytokines by human peripheral blood mononuclear cells in vitro and up-regulate cell surface markers on monocytes, NK cells and B cells. In addition, AGPs provide non-specific resistance to challenge with viral and bacterial pathogens when administered to the upper airways of mice. Structure-activity relationship studies have shown that the activation of innate immune effectors by AGPs depends primarily on the length of the secondary acyl chains and the nature of the functional group attached to the aglycon component. Moreover, AGPs can act as potent adjuvants for mucosal administration of vaccine antigens, enhancing both antigen-specific antibody and cell-mediated immune responses. Thus, by combining the adjuvant and non-specific resistance induction properties of AGPs it may be possible to generate mucosal vaccines that provide innate protection immediately following administration together with long-term acquired immunity.


On the vital role of fluid movement in organisms and cells: a brief historical account from Harvey to Coulson, extending the hypothesis of circulation.
The importance of the orchestrated movement of substrates over multicatalytic enzymes, topographically arranged for maximum efficacy for metabolic function, means that the organization of the body right down to the subcellular level is based upon the principle of perfusion for most normal living processes. The history of the development of this idea, which is contrary to the received wisdom arising and still persisting since the early days of biochemistry, will be followed from the time when the overall need for a circulation at the gross level was fully appreciated, extending the argument through a historical perspective to include the control of flow within the individual cell. Life, seen from this new perspective, seems to be inherently dependent upon this principle to such an extent that it leads to a clearer distinction between the living and the dead, and provides a framework for more critical experiments concerning control mechanisms in the cell.


Empirical models for dosage optimization of four beta-lactams in critically ill septic patients based on therapeutic drug monitoring of amikacin.
The study aims to develop empirical models able to predict the pharmacokinetics (PK) of four beta-lactams using the amikacin (AMK) therapeutic drug monitoring (TDM), in order to optimize their dosage regimens. 69 critically ill septic patients were included. All received a first dose of AMK combined with piperacillin/tazobactam, ceftazidime, cefepime or meropenem. A multivariate analysis was performed to predict the beta-lactam PK using AMK PK parameters estimated from TDM and using pathophysiological variables. An optimal prediction model was identified for each PK parameter of each beta-lactam. The best predictor of each model was one of the AMK PK parameters estimated from TDM. Other variables included colloid solution, renal and hepatic biomarkers, age and body weight. PK of the four beta-lactams could be easily and rapidly predicted in critically ill septic patients using the AMK TDM. These predictions could improve the beta-lactam dosages in clinical practice.


Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4.
The kidney has been widely exploited as a model system for the study of tissue inductions regulating vertebrate organogenesis. Kidney development is initiated by the ingrowth of the Wolfian duct-derived ureteric bud into the presumptive kidney mesenchyme. In response to a signal from the ureter, mesenchymal cells condense, aggregate into pretubular clusters and undergo an epithelial conversion generating a simple tubule. This then undergoes morphogenesis and is transformed into the excretory system of the kidney, the nephron. We report here that the expression of Wnt-4, which encodes a secreted glycoprotein, correlates with, and is required for, kidney tubulogenesis. Mice lacking Wnt-4 activity fail to form pretubular cell aggregates; however, other aspects of mesenchymal and ureteric development are unaffected. Thus, Wnt-4 appears to act as an autoinducer of the mesenchyme to epithelial transition that underlies nephron development.


Spreading depression in elasmobranch cerebellum.
Spreading depression (SD) occurs in the cerebellum of an elasmobranch fish, the skate (Raja erinacea, Raja ocellata). The elasmobranch cerebellum, because of its unique separation of granular form molecular layer, provides an excellent opportunity to study the characteristics of SD in two distinct neuronal populations. Both the DC potential shifts and changes in neuronal activity effected by SD were analyzed. The SD DC potential shifts in both layers closely resembled those in mammalian cerebral cortices. Consisting of a predominantly negative extracellular potential shift, they were typically 1--10 min in duration and reached 5--40 mV peak amplitudes. The largest negative shifts were found in the granular layer, without any consistent positive phases in the white matter, molecular, or granular layers. The SD propagated radially from surface electrical stimulation at 0.78 mm/min (+/- 0.16, n = 8) in the molecular layer and 0.43 mm/min (+/- 0.17, n = 8) in the granular layer at 15 degrees C. At 18 degrees C, the molecular layer propagatory velocity was 1.1 mm/min (+/- 0.12, n = 20) while, at 10 degrees C, it was 0.52 mm/min (+/- 0.21, n = 20), suggesting a temperature-dependent Q10 factor of 2. A profound depression of both spontaneous and evoked neuronal activity accompanied the DC potential shift. Activation of Purkinje cells antidromically, white matter, and granular layer neurons was typically abolished by the peak of the negative DC shift. However, a significant increase in granular layer excitability often followed the neuronal depression, remaining so far up to an hour. Repeated waves of SD sometimes occurred in the absence of neuronal recovery. A similar post-SD excitability increase was not seen in molecular layer neurons. Intracellular recordings from Purkinje cells revealed a spontaneous burst of action potentials at the onset of SD, closely followed by a depolarization of membrane potential from an average of -64 mV (+/- 12 mV, n = 3) to -11 mV (+/- 5 mV, n = 3).


Pupillary responses and attentional allocation problems on the backward masking task in schizophrenia.
Early visual information processing impairment has consistently been found on the backward masking task in patients with schizophrenia, but the nature of this impairment remains unclear. Pupillometry was used to measure attentional allocation during visual backward masking task performance in patients with schizophrenia (n=16) and nonpsychiatric controls (n=16). The extent of pupil dilation recorded during a cognitive task reflects the processing load placed on the nervous system by the task. Schizophrenia patients detected significantly fewer targets than controls only when the stimulus onset asynchrony (SOA) between targets and masks reached 317 ms. For both groups, peak pupil dilation responses were also significantly larger in the 317 ms SOA condition relative to a no-mask condition, suggesting that the processing load of the 317 SOA masking condition was greater than the no-mask condition. In addition, a principal components analysis of pupillary response waveforms identified time-related factors that appeared to differentially index attentional allocation to targets vs. masks. Patients with schizophrenia showed less dilation than controls on a middle factor that appeared to index attentional allocation to targets, but patients showed greater dilation than controls on a late factor that appeared to index attentional allocation to masks. That is, controls attended more to targets than to masks, but patients attended more to masks than to targets. These findings suggest that masking impairments at SOA intervals greater than 100-200 ms may be due abnormalities in attentional allocation mechanisms.


[Comparison of preoperative and postoperative findings after stress incontinence surgery in women (author's transl)].
The authors attempt to assess success of surgery in 44 women with stress incontinence treated with colporrhaphia ant. et post. with/without vaginal hysterectomy, by evaluating preoperative and postoperative findings. Examination comprised, after detailed anamnesis, besides general gynaecological examination and examination of urine for pathological constituents, the following methods: simultaneous urethrocystometry, cystometry, urethrocystography, electromyography of the sphincter system, as well as uroflowmetry. It was found that despite subjectively reported success of operation there was often no direct correlation to the actual, objective findings. This underlines once again that assessment of the result of surgery is possible only via application of a wide range of diagnostic procedures postoperatively with the same methods. The results obtained are discussed with reference to reports published in medical literature.


Nanogold: a quantitative phase map.
The development of the next generation of nanotechnologies requires precise control of the size, shape, and structure of individual components in a variety of chemical and engineering environments. This includes synthesis, storage, operational environments and, since these products will ultimately be discarded, their interaction with natural ecosystems. Much of the important information that determines these properties is contained within nanoscale phase diagrams, but quantitative phase maps that include surface effects and critical diameter (along with temperature and pressure) remain elusive. Here we present the first quantitative equilibrium phase map for gold nanoparticles together with experimental verification, based on relativistic ab initio thermodynamics and in situ high-resolution electron microscopy at elevated temperatures.


Applying the 3Rs: A Case Study on Evidence and Perceptions Relating to Rat Cage Height in the UK.
This article investigates the barriers to implementing higher caging in animal research establishments in the UK. The use of animals in research and testing in the UK is regulated by the Animals (Scientific Procedures) Act 1986, which sets out how animal experiments must be licensed and regulated. Within this, the Code of Practice currently allows laboratory rats to be housed in cages that are 20 cm high, even though adults can rear up to 30 cm. Most adult rats therefore cannot stand upright in 'standard' cages. We found that the main factors hindering the implementation of higher caging were classified into five different groups; health and safety, financial, animal welfare, scientific, and 'human'. Suggestions to overcome these barriers are provided, as well as alternative animal welfare changes that can be put into place. We conclude that much of the desired evidence for moving to higher cages is already available, and therefore the focus should be on education and improving access to the existing evidence, in order to encourage facilities to work around existing financial and health and safety concerns.


Effect of aciclovir on the replication of herpes simplex virus type 1 in MA-104 cell line resistant to aciclovir.
A culture of monkey kidney cells (MA-104) resistant to aciclovir (CAS 59277-89-3) was established. The resistant cells were continuously grown in medium containing 200 mumol/l aciclovir whereas normal cells died in such medium. The doses of aciclovir required for 50 and 90% reduction in virus yield were for several Herpes simplex virus Type 1 clinical isolates up to 5-fold higher in resistant than in normal MA-104 cells; in contrast, doses required for 99% reduction in virus yield could be as much as 50-fold higher in the resistant cells. Virus yields developed in the presence of 30 mumol aciclovir in culture medium were at least 10(3)-fold higher in resistant than in normal MA-104 cells. The results showed that the antiviral effect of aciclovir may be significantly decreased in the cell line which developed resistance to aciclovir.


Resveratrol derivatives from Vatica albiramis.
Three new stilbene derivatives, albiraminols A (1) (resveratrol hexamer), B (2) (resveratrol dimer), and vatalbinoside F (3) (mono-glucoside of resveratrol dimer), along with malibatol were isolated from acetone soluble portions of the stem of Vatica albiramis. The structures of the isolates were established on the basis of spectroscopic analyses, including a detailed NMR spectroscopic investigation. The biosynthetic aspects of the isolates are discussed in this paper. Compound 1 is composed of tetrameric resveratrol (vaticanol B (1A)) and dimeric resveratrol (1B) and is the first instance of the resveratrol derivative bearing a 5,6,11,12-tetrahydro-5,11-epoxydibenzo[a,e][8]annulene ring system. Compound 2 possesses a novel 4,5-dihydro-13-oxabenzo[3,4]azuleno[7,8,1-jkl]phenanthrene skeleton in the framework.


The chicken serotonin transporter discriminates between serotonin-selective reuptake inhibitors. A species-scanning mutagenesis study.
The serotonin transporter (SERT) belongs to a family of sodium chloride-dependent transporters responsible for uptake of amino acids and biogenic amines from extracellular spaces. SERT represents the main pharmacological target in the treatment of several clinical conditions, including depression and anxiety. Serotonin-selective reuptake inhibitors and tricyclic antidepressants are the most predominantly prescribed drugs in the treatment of depression. In addition to antidepressants also psychostimulants, like cocaine and amphetamines, are important SERT antagonists. In the present study, we report the cloning and characterization of chicken SERT. Although the uptake kinetic was very similar to human SERT, the pharmacological profiles differed considerably for the two species. We find that chicken SERT is capable of discriminating between different serotonin-selective reuptake inhibitors; thus, the potency of S-citalopram and paroxetine is reduced more than 40-fold. A cross-species chimera strategy was undertaken and followed by species-scanning mutagenesis. Differences in pharmacological profiles were tracked to amino acid residues 169, 172, and 586 in human SERT. Structure-activity studies on structurally related compounds indicated that species divergences in drug sensitivity between human and chicken SERT were arising from differences in coordination or recognition of an important aminomethyl pharmacophoric substructure, which is shared by all high affinity antidepressants. Consequently, we suggest that Ala(169) and Ile(172) of human SERT are important residues in sensing the N-methylation state of SERT antagonists.


Tumor interaction with hemostasis: the rationale for the use of platelet inhibitors and anticoagulants in the treatment of cancer.
Clinical and experimental observations have firmly established the concept of a two-way interaction between malignancy and the hemostatic system. On the one hand, certain tumors can activate platelets and the coagulation mechanism in vivo, on the other, a convincing case has been made for the involvement of platelets and fibrin in tumor growth and metastasis. A large number of clinical and experimental studies have been conducted in order to test the efficacy of platelet inhibitors and anticoagulants as adjuvants in the treatment of cancer. Antiplatelet drugs gave variable results, depending on the drug and the tumor system tested. Prostaglandin synthetic pathways by both the host and tumor seem to be an important determinant in the response to platelet function inhibitors. Of the various anticoagulants tested, the coumarin derivatives gave somewhat consistent antitumor effect in certain human and experimental cancer. The antitumor effect of oral anticoagulants does not appear to be a primary drug effect and seems related to their role as vitamin K antagonists. It should be emphasized that although the antitumor potential of antithrombotic agents is a subject of keen interest at the present, their use in treating human cancer is still controversial.


[Theoretical and methodological uses of research in Social and Human Sciences in Health].
The current article aims to map and critically reflect on the current theoretical and methodological uses of research in the subfield of social and human sciences in health. A convenience sample was used to select three Brazilian public health journals. Based on a reading of 1,128 abstracts published from 2009 to 2010, 266 articles were selected that presented the empirical base of research stemming from social and human sciences in health. The sample was classified thematically as "theoretical/ methodological reference", "study type/ methodological design", "analytical categories", "data production techniques", and "analytical procedures". We analyze the sample's emic categories, drawing on the authors' literal statements. All the classifications and respective variables were tabulated in Excel. Most of the articles were self-described as qualitative and used more than one data production technique. There was a wide variety of theoretical references, in contrast with the almost total predominance of a single type of data analysis (content analysis). In several cases, important gaps were identified in expounding the study methodology and instrumental use of the qualitative research techniques and methods. However, the review did highlight some new objects of study and innovations in theoretical and methodological approaches.


Complexometric titration of Ti(IV) with 2-(5-chloro-2-pyridylazo)-5-dimethylaminophenol as indicator.
A method for determination of titanium by a reverse titration with EDTA in the presence of hydrogen peroxide, with 2-(5-chloro-2-pyridylazo)-5-dimethylaminophenol as indicator, is presented; use of the method for analysis of titanium paints is also described.


Interaction of replicase components between Cucumber mosaic virus and Peanut stunt virus.
Cucumber mosaic virus (CMV) and Peanut stunt virus (PSV) each have genomes consisting of three single-stranded RNA molecules: RNA 1, 2 and 3. RNAs 1 and 2 encode the 1a and 2a proteins, respectively, which are necessary for replication of the viral genome. Although RNA 3 is exchangeable between CMV and PSV, exchange of RNA 1 and 2 between the two viruses has been unsuccessful. In this study, reassortants containing PSV RNA 1 and CMV RNA 2 together with RNA 3 of CMV or PSV were shown to be able to replicate their genomic RNA, but not to transcribe subgenomic RNA 4 in tobacco protoplasts. Conversely, the reassortant consisting of CMV RNA 1 and PSV RNA 2 together with RNA 3 of CMV or PSV could not replicate. Subsequently, a yeast two-hybrid system was used to analyse the in vivo interaction between the 1a and 2a proteins. The C-terminal half of PSV-1a protein interacted with the N-terminal region of 2a protein of both PSV and CMV, but the C-terminal half of CMV-1a and the N-terminal region of PSV-2a did not interact. These results suggest that RNA replication in the interspecific reassortant between CMV and PSV requires compatibility between the C-terminal half of the 1a protein and the N-terminal region of the 2a protein, and this compatibility is insufficient for transcription of subgenomic RNA 4.


Tuberous sclerosis: a primary pathology of astrocytes?
Cortical tubers are epileptogenic lesions in patients with tuberous sclerosis complex (TSC). Giant cells and dysplastic neurons are pathological hallmarks of cortical tubers. Severe astrogliosis, which is invariably present in tubers, has attracted much less attention. We hypothesize that the development of astrogliosis in cortical tubers constitutes a primary pathology of astrocytes and is directly related to TSC 1/2 mutations. To begin to test this hypothesis, we performed immunohistochemical and electron microscopic analysis of brain tuber tissue resected from epileptic TSC patients. We compared alterations in tuber astrocytes to those found in other acute and chronic human epilepsy pathologies. We found that astrogliosis in tubers is comprised of a mixture of "gliotic" and "reactive" astrocytes. The majority of tuber astrocytes are "gliotic" astrocytes that are morphologically and immunophenotypically similar to astrocytes in areas of gliosis in hippocampal sclerosis (HS). However, specific immunostaining features differentiate TSC gliosis from HS gliosis. "Reactive" tuber astrocytes are large-sized, vimentin positive cells in the vicinity of giant cells that show activation of the mammalian target of rapamycin (mTOR) pathway, consistent with mutated TSC gene function. These cells resemble acutely reactive human astrocytes seen in tissue resected from depth electrode implantation patients. Oligodendrocytes and NG2 expressing glial cells do not have any detectable alterations within tubers. We conclude that astrocytes are the type of glial cell selectively impacted in cortical tuber pathology. We propose that tubers may be dynamic lesions, with progression of astrocytes over time from "reactive" to "gliotic." Tuber astrogliosis in TSC may represent a genetic "model" of gliosis that is phenotypically similar to gliosis seen in acquired human pathologies.