Epidermal growth factor receptor binding is affected by structural determinants in the toxin domain of transforming growth factor-alpha-Pseudomonas exotoxin fusion proteins.
TGF-alpha-PE40 is a hybrid protein composed of transforming growth factor-alpha (TGF-alpha) fused to a 40,000-dalton segment of Pseudomonas exotoxin A (PE40). This hybrid protein possesses the receptor-binding activity of TGF-alpha and the cell-killing properties of PE40. These properties enable TGF-alpha-PE40 to bind to and kill tumor cells that possess epidermal growth factor (EGF) receptors. Unexpectedly, TGF-alpha-PE40 binds approximately 100-fold less effectively to EGF receptors than does native TGF-alpha (receptor-binding inhibition IC50 = 540 and 5.5 nM, respectively). To understand the factors governing receptor binding, deletions and site-specific substitutions were introduced into the PE40 domain of TGF-alpha-PE40. Removal of the N-terminal 59 or 130 amino acids from the PE40 domain of TGF-alpha-PE40 improved receptor binding (IC50 = 340 and 180 nM, respectively) but decreased cell-killing activity. Substitution of alanines for cysteines at positions 265 and 287 within the PE40 domain dramatically improved receptor binding (IC50 = 37 nM) but also decreased cell-killing activity. Similar substitutions of alanines for cysteines at positions 372 and 379 within the PE40 domain did not significantly affect receptor-binding or cell-killing activities. These studies indicate that the PE40 domain of TGF-alpha-PE40 interferes with EGF receptor binding. The cysteine residues at positions 265 and 287 of PE40 are responsible for a major part of this interference.


Boundary effects in the critical scaling of entanglement entropy in 1D systems.
We present exact diagonalization and density matrix renormalization group results for the entanglement entropy of critical spin-1/2 XXZ chains. We find that open boundary conditions induce an alternating term in both the energy density and the entanglement entropy which are approximately proportional, decaying away from the boundary with a power law. The power varies with anisotropy along the critical line and is corrected by a logarithmic factor, which we calculate analytically, at the isotropic point. A heuristic resonating valence bond explanation is suggested.


[Antimutagenic activity of the enzyme preparation "binase" in microbial test systems].
The occurrence of microorganisms and the rates of terminal biogenic reduction of sulfates and synthesis of methane in stratal waters in deposit 302 of Bashkir Carboniferous deposition at the Romashkinskoe oil field were studied. It was shown that deposit 302 is a dynamic, highly reduced ecosystem containing sulfates and hydrogen sulfide in considerable concentrations, in which active biogenic processes occur. Sulfate reduction is a dominating anaerobic process by which the organic constituents of oil are transformed. The sulfate-reducing microflora is quite varied and characterized by high metabolic potentials. Enriched cultures, which can oxidize many organic substances, such as benzoate, acetate, ethanol, or lactate, at the expense of reduction of sulfates and ferric ion, were isolated from the samples extracted from deposit 302. It was suggested that the sulfate-reducing microflora might be responsible not only for sulfate reduction in the stratum but also for mobilization of part of insoluble iron oxides in the oil trap rock. The findings indicate that the dissimilation sulfate- and iron-reducing bacteria can contribute to the geochemistry of organic and mineral compounds in underground ecosystems.


Effect of humic compost on the adsorption of cadmium (II) in aqueous medium.
The humic compost obtained from the treatment of tobacco from smuggled cigarettes (SCT) and industrial sewage sludge (ISS) was evaluated as adsorbent for Cd (II) in aqueous solution, for possible decontamination of water resources. Optimum conditions were found at pH 5 and a 3 g/L adsorbent concentration, which presented 92% Cd (II) removal and maximum adsorption capacity of 28.546 mg/g. The pseudo-second-order kinetic model presented the best fit, pointing 120 min as the time needed to attain a steady state. FTIR and EDX results suggest the formation of coordinated Cd (II) bonds by functional groups between the compost and the solution. The results obtained in real samples showed that, even under different environmental conditions, the Cd (II) adsorption varied between 80.05 and 91.61%. The results indicated that the compost evaluated can be used for remediation of Cd (II)-contaminated water resources.


Interventions targeting HIV-infected risky drinkers: drops in the bottle.
Alcohol use is common among people infected with HIV and may contribute to adverse consequences such as reduced adherence to treatment regimens and increased likelihood of risky sexual behaviors. Therefore, researchers and clinicians are looking for treatment approaches to reduce harmful alcohol consumption in this population. However, clinical trials of existing treatment models are scarce. A literature review identified only 11 studies that included HIV-infected patients with past or current risky alcohol use and which targeted alcohol use and other health behaviors. Four studies focusing on HIV-infected participants with alcohol problems found mixed effects on adherence and on alcohol use. Five clinical trials included at least 10 percent of HIV-infected subjects who use alcohol; of these, only one reported significant evidence of a favorable impact on alcohol consumption. Finally, two trials targeting alcohol users at high risk for HIV infection identified treatment effects that were not sustained. Taken together, these findings provide limited evidence of the benefit of behavioral interventions in this population. Nevertheless, these studies give some guidance for future interventions in HIV-infected patients with alcohol problems.


The metabolism and pharmacokinetics of 14C-cetirizine in humans.
This study investigated the metabolism and pharmacokinetics of cetirizine, a new H1-receptor antagonist. Single oral doses of 14C-cetirizine dihydrochloride (10 mg) in aqueous solution were administered to six healthy male volunteers. The drug was rapidly absorbed: The peak mean concentration of radioactivity (359 ng-equivalents/mL) and of unchanged drug (341 ng/mL) were achieved within one hour. Mean concentrations of cetirizine declined biexponentially and had a mean elimination half-life of 7.4 hours. The drug was excreted quite rapidly, with 60% of the dose recovered in the 24-hour urine. An additional 10% was excreted in urine over the next four days. Approximately 10% of the dose was excreted in feces over the five-day study period. The dose was excreted mainly as the unchanged drug. Examination of the radioactive compounds present in the plasma, and excreted in the urine and feces indicate that there is little metabolism of cetirizine. One minor metabolite, formed by oxidative O-dealkylation of the cetirizine side chain, was detected in plasma and feces.


Automated high throughput pKa and distribution coefficient measurements of pharmaceutical compounds for the SAMPL8 blind prediction challenge.
The goal of the Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL) challenge is to improve the accuracy of current computational models to estimate free energy of binding, deprotonation, distribution and other associated physical properties that are useful for the design of new pharmaceutical products. New experimental datasets of physicochemical properties provide opportunities for prospective evaluation of computational prediction methods. Here, aqueous pKa and a range of bi-phasic logD values for a variety of pharmaceutical compounds were determined through a streamlined automated process to be utilized in the SAMPL8 physical property challenge. The goal of this paper is to provide an in-depth review of the experimental methods utilized to create a comprehensive data set for the blind prediction challenge. The significance of this work involves the use of high throughput experimentation equipment and instrumentation to produce acid dissociation constants for twenty-three drug molecules, as well as distribution coefficients for eleven of those molecules.


Elucidating the immunological effects of 5-azacytidine treatment in patients with myelodysplastic syndrome and identifying new conditional ligands and T-cell epitopes of relevance in melanoma.
This review is focused on research within three different areas of tumor immunology: discovery of new T-cell epitopes and a new immunological antigen (reported in Paper I and II), elucidation of the immunological effects of treatment with a hypomethylating drug (reported in Paper III) and discovery of new conditional ligands (reported in Paper IV). Many melanoma-associated T-cell epitopes have been described, but 45% of these are restricted to human leukocyte antigen (HLA)-A2, leaving the remaining 36 different HLA molecules with only a few described T-cell epitopes each. Therefore we wanted to expand the number of T-cell epitopes restricted to HLA-A1, -A3, -A11 and -B7, all HLA molecules frequently expressed in Caucasians in Western Europe and Northern America. In Paper I we focused on the proteins gp100, Mart1, MAGE-A3, NY-ESO-1, tyrosinase and TRP-2, all melanoma-associated antigens frequently recognized by T cells from HLA-A2 patients. On contrary, in Paper II we wanted to investigate the protein Nodal as a novel immunological target. We took advantage of a T-cell epitope mapping platform in which HLA ligands are predicted by computer-based algorithms, further tested in the laboratory by an ELISA-based method and used for flow cytometry-based detection of specific T-cell responses by use of combinatorial encoded major histocompatibility (MHC) class I multimers. This procedure resulted in 127 (Paper I) and 32 (Paper II) confirmed HLA ligands, respectively, which we used for screening of the T-cell recognition within peripheral blood mononuclear cell samples from melanoma patients. As spontaneous tumor-specific T-cell responses tend to be of very low frequency and probably below the detection threshold of the method, we incorporated a T-cell enrichment step prior to the detection of these responses. Our screening of 39 melanoma patients resulted in 26 (17 different) T-cell responses against the common melanoma-associated antigens and 10 (8 different) T-cell responses against Nodal. We were further able to show processing and presentation on the cell-surface in K562 and melanoma cells expressing relevant protein and HLA molecules of four of these peptide sequences from tyrosinase, gp100 (2 peptides) and Nodal, respectively. However, one of the gp100 peptides has previously been described as a T-cell epitope. In addition to identifying new melanoma-associated T-cell epitopes we could thus describe Nodal as a new immunological antigen found of relevance in melanoma patients. In Paper III we wanted to investigate if the hypomethylating drug 5-azactytidine (Vidaza, Celgene Inc.) modulates the immune system in patients with myeloproliferative diseases. It has previ-ously been shown that 5-azacytidine-mediated demethylation of gene promoter regions results in enhanced transcription and expression of tumor suppressor genes and cancer-testis antigens. Cancer-testis antigens have frequently been recognized by T-cells in many cancers, and we hypothesized that 5-azacytidine treat-ment in the clinic would increase their frequency with resulting enhanced anti-tumor reactivity. We investigated separately the effect on T cells and tumor cells, and found that tumor cells af-fected by the treatment were better recognized, resulting in higher numbers of activated T cells, than tumor cells not exposed to 5-azacytidine. No effects were observed on the T-cell population. A screen of the T-cell recognition of 43 cancer-testis antigens in blood from our patients revealed increased T-cell recognition upon start of therapy which, though, stabilized or declined at later time points. We further investigated the general immune effector and inhibitory cell populations and found only minor effects of drug exposure, suggesting that 5-azacytidine primarily affects the tumor cells. From these results we are currently initiating a phase I clinical trial of cancer-testis antigen-peptide vaccination in combination with 5-azacytidine therapy for patients with myeloproliferative diseases. In Paper IV we wanted to expand the library of conditional ligands for use with the UV light-mediated peptide-exchange method. This method enables high-throughput generation of MHC class I molecules with different peptide-specificities. These MHC monomers can be multimerized and used for detection of specific T cell populations by flow or mass cytometry. The HLA molecules are highly genetically variable and this necessitates unique design of conditional ligands for each HLA molecule. Thus, to screen for the T-cell recognition in a given setting within all patients or healthy donors present in a cohort, a broad library of conditional ligands is needed. We designed and evaluated conditional ligands for HLA-B*08:01, HLA-B*35:01 and HLA-B*44:02/03/05, all HLA-B molecules present in high frequency among Caucasians. In addition, we provided proof for the use of a conditional ligand first designed for HLA-B*15:02 in complex with HLA-B*15:01. We compared the staining patterns of HLA-B*15:01 and HLA-B*15:02 MHC multimers and found remarkable dissimilarities, although the two heavy chains in these MHC molecules only differ in a few amino acid positions.


The Italian scheme of External Quality Assessment for beta-thalassemia: genotyping and reporting results and testing strategies in a 5-year survey.
The Italian scheme of External Quality Assessment for beta-thalassemia started in 2001 as part of a project twice funded by the Italian Ministry of Health and coordinated by the Istituto Superiore di Sanità. To date, five trials have been performed (2001-2004 and 2006). The aim of the Italian scheme is to help public laboratories in improving and reaching a high standard of quality when performing a molecular test. Many laboratories took part in the 5-year project, and their participation was constant during the whole period. The aims of this paper are to describe the genotyping and reporting results as well as focusing on the techniques and the testing strategies adopted to detect mutations. Almost 99% of the alleles analyzed were correctly detected by laboratories, while 0.33% of the analyses gave a wrong result. Reverse dot blot was the most used technique, and it was always used in the strategies adopted by laboratories to detect mutations. The reports sent by laboratories showed incompleteness and heterogeneity; thus, a new model for written reports has been introduced since 2004. It will be interesting to monitor the effects of the reporting model and the output of this educational action in the future.


[Production of 14-substituted derivatives of carminomycin and rubomycin].
14-Bromocarminomycin and 14-bromorubomycin were treated with alkali metal salts and nitrogen heterocycles to obtain 14-acetoxycarminomycin, 14-octamoylhydroxycarminomycin, 14-salicyloylhydroxycarminomycin, 14-salicyloylhydroxyrubomycin, 14-chinaldinoylhydroxyrubomycin and rubomycin 14-N-phthalimide, rubomycin 14-N-pyridinium bromide and 14-N-imidazolylrubomycin. It was shown that the reaction rate of the nucleophilic substitution in the acetone medium could be increased with the use of crown ethers of sodium iodide. Under such conditions 14-iodinecarminomycin and 14-iodinerubomycin, two intermediate products, partially reduced to the initial antibiotics, i.e. carminomycin and rubomycin. 14-Acetoxycarminomycin had the highest activity against Bac. mycoides, used as a test microbe. It amounted to 50 per cent, while the activity of the other derivatives did not exceed 25 per cent of the activity of the initial antibiotics.


The association of parity with osteoarthritis and knee replacement in the multicenter osteoarthritis study.
We evaluated the association of parity to both risk of knee replacement (KR) and knee osteoarthritis (OA). The NIH-funded Multicenter Osteoarthritis Study (MOST) is a longitudinal observational study of persons age 50-79 years with either symptomatic knee OA or at elevated risk of disease. Baseline and 30-month knee radiographic OA (ROA) was defined as Kellgren/Lawrence (K/L) grade ≥2 or KR. Women were grouped based by number of births: 0; 1 (reference group); 2; 3; 4; and 5 or more. We examined the relation of parity to the incidence over 30 months of ROA and KR using a Poisson regression model. Generalized estimating equations (GEE) were used to control for correlation between two knees within a subject. We adjusted for age, BMI, race, education, occupation, baseline estrogen use, clinical site, injury, and for KR analyses WOMAC pain and use of pain medication. Among 1618 women who reported parity information, mean age was 62.6 years, mean BMI 30.7 kg/m(2), mean WOMAC pain subscale score 3.7 at baseline. There were 115 KRs and 134 cases of incident knee ROA over 30 months. The relative risk of incident KR was 2.7 times as high (95% CI: 1.0, 7.3) and relative risk of incident knee ROA was 2.6 times as high (95% CI: 1.2, 5.3) among women with five to 12 children compared with those with one birth. Parity in women at risk for OA is associated with both incident ROA and KR, particularly for those with more than four children.


Geographic variation in utilization of cataract surgery.
Cataract surgery is the most frequently performed surgical procedure on Medicare beneficiaries, with an annual cost to the Medicare program of more than $3.4 billion. In this study, the relationship between demographic, environmental, and provider-related factors, and the likelihood that cataract surgery will be performed on a Medicare beneficiary were assessed. The association between likelihood of cataract surgery and patient age, sex, race, income, and latitude of residence was examined, as was the association with the supply of ophthalmologists and optometrists in each region, and the allowed charge for cataract surgery and cost of practice in a region. This cross-sectional, population-based study used administrative data. Both regional models, using least-squares regression and person-based models, using logistic regression were employed. A random 5% sample of 1986 and 1987 Medicare beneficiaries, 65 years of age and older, were included in the study. Medicare beneficiaries who lacked continuous Part A and Part B coverage during 1986 and 1987, or who were enrolled in a health maintenance organization at any time during this 2-year period of observation were excluded from the study to make certain that complete utilization data were available for each individual. Rate of cataract surgery per 1,000 Medicare beneficiaries in each Bureau of Economic Analysis Economic Area (BEAEA) and the likelihood of an individual with particular characteristics undergoing cataract surgery were determined in separate regression models. The mean annual rate of cataract surgery during 1986 and 1987 in the 181 BEAEAs was 25.4 surgeries per 1,000 persons 65 years of age or older (standard deviation = 6.2, coefficient of variation = 0.24). Both the regional model and the person-based model detected an association between a higher rate of and personal likelihood of cataract surgery and female gender, more southerly latitude, higher concentration of optometrists per 1,000 Medicare beneficiaries, and higher allowed charge for cataract surgery, after adjusting for variation in practice expense. The person-based model additionally demonstrated that increased likelihood of undergoing cataract surgery was associated with increasing age from 65 to 94 years, white race, and living in a zip-code area with mean income greater than $15,000. Neither analysis detected a statistically significant association between the concentration of ophthalmologists per 1,000 Medicare beneficiaries and the regional rate of, or an individual's likelihood of, cataract surgery. Compared with the geographic variation in provision of other surgical procedures, the variation in cataract surgery across large geographic areas observed in this analysis was relatively low.(ABSTRACT TRUNCATED AT 400 WORDS)


Human umbilical cord expresses several vasoactive peptides involved in the local regulation of vascular tone: protein and gene expression of Orphanin, Oxytocin, ANP, eNOS and iNOS.
Full-term human umbilical cord contains three blood vessels: two arteries coiled around a vein and surrounded by Wharton's jelly, a mucous tissue with few mesenchymal stromal cells and abundant extracellular matrix. Umbilical vessels lack innervations, thus endothelial cells must play a role in the control of blood flow. The aim of this study was to investigate in human umbilical cord the expression of five peptides that could be involved in the regulation of vascular tone: Orphanin FQ, Oxytocin, Atrial Natriuretic Peptide (ANP), endothelial Nitric Oxide Synthase (eNOS) and inducible Nitric Oxide Synthase (iNOS). The expression of these molecules in full-term human umbilical cord was investigated through immunohistochemistry and RT-PCR. Immunoreactivity for Orphanin FQ was detected in Wharton's jelly, vessel musculature and endothelium; Oxytocin, ANP and eNOS were expressed by the umbilical epithelium, Wharton's jelly and endothelium, whereas iNOS only by endothelial cells. RT-PCR analysis showed transcriptional expression of Oxytocin, ANP and eNOS mRNAs. The presence of Orphanin, Oxytocin, ANP, eNOS and iNOS proteins was identified in the human umbilical cord. mRNA expression for Oxytocin, ANP and eNOS suggest that these molecules are synthesized by umbilical cord cells themselves. The expression of these vasoactive molecules could be part of a general mechanism locally regulating vascular tone.


Total body vascular capacitance changes during high intracranial pressure in dogs.
The active capacitance response to increased intracranial pressure (Pic) was studied in nine chloralose-anesthetized dogs. The vena cavae were cannulated and drained into a reservoir as blood was pumped at a constant flow (Q) into the right atrium. Central blood volume was determined as Q times the mean transit time of dye from the right atrium to the aortic root. Arterial compliance (Ca) was determined from the monoexponential decay of systemic arterial pressure (SAP) during vagal cardiac arrest to compute changes in arterial volume (delta SAP X Ca). Atropine was administered to prevent bradycardia and dangerous, constant cardiac output-induced increases in pulmonary arterial (PAP) and right and left atrial pressures. Blood volume shifts indicative of active venoconstriction, included changes in reservoir, central, and arterial volumes during Pic of 100-200 mmHg. Raised Pic, after atropine, induced a tachycardia, increased systemic and pulmonary resistances, and increased SAP and PAP. Venoconstriction caused marked blood shifts between 125 and 200 mmHg Pic. The extrapolated response threshold was about 112 mmHg. In the most sensitive range, venoconstriction amounted to 3.9 ml X kg-1 per 25-mmHg change in Pic. These results indicate that intense active capacitance vessel constriction is an important part of cardiovascular hemostasis during rapidly increased intracranial pressure.


Engineered contrast agents in a single structure for T1-T2 dual magnetic resonance imaging.
The development of contrast agents (CAs) for Magnetic Resonance Imaging (MRI) with T1-T2 dual-mode relaxivity requires the accurate assembly of T1 and T2 magnetic centers in a single structure. In this context, we have synthesized a novel hybrid material by monitoring the formation of Prussian Blue analogue Gd(H2O)4[Fe(CN)6] nanoparticles with tailored shape (from nanocrosses to nanorods) and size, and further protection with a thin and homogeneous silica coating through hydrolysis and polymerization of silicate at neutral pH. The resulting Gd(H2O)4[Fe(CN)6]@SiO2 magnetic nanoparticles are very stable in biological fluids. Interestingly, this combination of Gd and Fe magnetic centers closely packed in the crystalline network promotes a magnetic synergistic effect, which results in significant improvement of longitudinal relaxivity with regards to soluble Gd3+ chelates, whilst keeping the high transversal relaxivity inherent to the iron component. As a consequence, this material shows excellent activity as MRI CA, improving positive and negative contrasts in T1- and T2-weighted MR images, both in in vitro (e.g., phantom) and in vivo (e.g., Sprague-Dawley rats) models. In addition, this hybrid shows a high biosafety profile and has strong ability to incorporate organic molecules on the surface with variable functionality, displaying great potential for further clinical application.


Advances in Implantable Microelectrode Array Insertion and Positioning.
Microelectrode arrays offer a means to probe the functional circuitry of the brain and the promise of cortical neuroprosthesis for individuals suffering from paralysis or limb loss. These devices are typically comprised of one or more shanks incorporating microelectrode sites, where the shanks are positioned by inserting the devices along a straight path that is normal to the brain surface. The lack of consistent long-term chronic recording technology has driven interest in novel probe design and approaches that go beyond the standard insertion approach that is limited to a single velocity or axis. This review offers a description of typical approaches and associated limitations and surveys emergent methods for implantation of microelectrode arrays, in particular those new approaches that leverage embedded microactuators and extend the insertion direction beyond a single axis. This review paper surveys the current technologies that enable probe implantation, repositioning, and the capability to record/stimulate from a tissue volume. A comprehensive literature search was performed using PubMed, Web of Science, and Google Scholar. There has been substantial innovation in the development of microscale and embedded technology that enables probe repositioning to maintain quality recordings in the brain. Innovations in material science have resulted in novel strategies for deployable structures that can record from or stimulate a tissue volume. Moreover, new developments involving magnetically steerable catheters and needles offer an alternative approach to "pull" rather than "push" a probe into the tissue. We envision the emergence of a new generation of probes and insertion methodologies for neuromodulation applications that enable reliable chronic performance from devices that can be positioned virtually anywhere in the brain.


Five-Year Predictors of Insulin Initiation in People with Type 2 Diabetes under Real-Life Conditions.
We performed a real-life analysis of clinical and laboratory parameters, in orally treated T2DM patients aiming at identifying predictors of insulin treatment initiation. Overall, 366955 patients (55.8% males, age 65 ± 11 years, diabetes duration 7 ± 8 years) were followed up between 2004 and 2011. Each patient was analyzed step-by-step until either eventually starting insulin treatment or getting to the end of the follow-up period. Patients switching to insulin showed a worse global risk profile, longer disease duration (10 ± 9 years vs. 6 ± 7 years, respectively; p < 0.001), higher HbA1c (8.0 ± 1.6% vs. 7.2 ± 1.5%, respectively; p < 0.001), higher triglycerides, a greater prevalence of arterial hypertension, antihypertensive, lipid-lowering and aspirin treatment, a higher rate of nonproliferative/proliferative retinopathy, and a nearly 4 times lower prevalence of the "diet alone." They also showed a higher prevalence of subjects with eGFR < 60 ml/min/1.73 m2 (24.0% vs. 16.2%, respectively; p < 0.001). Multivariate analysis identified diabetes duration, HbA1c, triglyceride and low HDL-C values, presence of retinopathy or renal dysfunction, and sulphonylurea utilization (the risk being approximately 3 times greater in the latter case) as independent predictors of insulin treatment initiation. LDL-C, lipid-lowering treatment, and overweight/obese seem to be protective. Results of tree analysis showed that patients on sulphonylurea, with high HbA1c, eGFR below 50 ml/min/1.73 m2, and at least 5-year disease duration, are at very high risk to start insulin treatment. We have to stick to this real-life picture, of course, until enough data are collected on patients treated with innovative medications which are expected to improve beta cell survival and further delay treatment-related insulin requirement.


[Biological signaling field in mammals (towards 110th anniversary of professor N.P. Naumov)].
Last 30 years the concept of biological signaling field, proposed by N.P. Naumov, developed, by and large, on the base of its main proposition according to which mammals leave on the landscape objects within a biogeocenosis some traces of their life activity forming, from generation to generation, the so called "matrix of stable elements" (Naumov, Goltzman et al., 1987). This matrix of stable elements is, really, a system of attractors. Within the context of signaling field, attractors are objects that attract animals' attention (Goltzman, Kruchenkova, 1999) and organize their usage of territory with all the resources that could be found on this territory. Elements of landscape attracting animals' attention form a system of attractors of the first order (basic attractors) (Nikol'skii, 2011). In perspective, as the signaling field develops, it is exactly them that form the basis of the matrix of stable elements which the system of unstable elements would be attached to. With regard to attractors of the first order, traces of mammals' life activity can be treated as attractors of the second order. Animals do not mark the resources themselves, but only the territory where those resources are located. Stable elements produce an olfactory-optic image of the territory that is used by every new generation of mammals. A supposition is brought forward that, similar to biological productivity and species diversity, stable elements of signaling field are indicative of respective stages of an ecological succession. The matrix of stable elements is most steady in mature, climax communities. As an example, main runs that are used by many mammal species can be considered. Last years, publications appear regularly in which main propositions of the signaling field concept are applied. A necessary condition for further development of the concept seems to be the establishment of new exploratory methods including modeling of processes that lead to the matrix of stable elements formation.


Midterm results with hepatectomy after preoperative chemotherapy in hepatoblastoma.
We evaluated the results of surgical treatment for hepatoblastoma in infants and children after intensive preoperative chemotherapy, with special reference to histology and extent of liver involvement. The clinical features of 10 children with hepatoblastoma were reviewed regarding response to neoadjuvant chemotherapy, histological subtypes, extent of hepatectomy, operative complications, and prognosis. Response to chemotherapy was measured by volumetric assessment of tumour size by computed tomography scan. Cisplatin and Adriamycin (PLADO regime) up to three cycles markedly reduced the tumour volume on computed tomography (mean regression rate 65.9%); alpha-foetoprotein (AFP) levels also decreased from an initial mean of 16,116.4 ng/ml to 2,050.9 ng/ml. Five patients underwent right hepatectomy, two had right trisegmentectomy, two had left hepatectomy, and one had left trisegmentectomy. Histopathology of resected specimens revealed foetal histology in four patients, poorly differentiated (anaplastic) subtype in three, and mixed histology with mesenchymal components and osteoid formation in three. There was 100% resectability including six unresectable tumours (prechemotherapy). Moreover, hepatic resection tended to be less invasive in patients whose tumours had been much reduced after preoperative chemotherapy. Preoperative administration of cisplatin and Adriamycin reduces the tumour size significantly so that a safe radical hepatectomy can be performed. It also allows early administration of postoperative chemotherapy. Although overall good results were obtained with the current protocol, we also document our experience of unfavourable outcomes in patients with bilobar tumours (despite trisegmentectomy), patients with tumours showing poor response to neoadjuvant chemotherapy, and patients with anaplastic histology. Overall, at a 60-month follow-up we report an 80% survival rate by a combined approach.


[Ambulatory pediatric surgery--possibilities and limits].
Pediatric surgical operations performed on an ambulatory basis in a practice are still rare in Germany. Prerequisites, indications, possibilities and limitations are presented. Some 869 operations were performed under general anesthesia within 21 months. Of the children 70% were under 5 years of age. The postoperative results were evaluated by means of a questionnaire in 352 children. Early complications occurred in five instances (1.4%) and late complications in one child (0.3%); hernia recurrence). Observing the possibilities and limitations, ambulatory pediatric surgery yields good results and takes the peculiarities of children into consideration.


Anonymity and live-donor transplantation: an ELPAT view.
Anonymity of donors or recipients in living-donor transplantation is a complex issue and practice varies widely. There are compelling arguments for maintaining anonymity of both parties before unspecified donor transplantation and specified indirect transplantation. After transplantation, there are still good reasons to avoid disclosure of identities. Although anonymity could be lifted if both parties explicitly request it, there are significant, potentially negative consequences of such an approach. Both donor and recipient should be counseled regarding these, and transplant teams should consider the considerable financial and psychosocial costs if problems are encountered as a result of contact. Given the recent rise in the number of unspecified living-donor transplants and through paired exchange schemes, it is vital that data are collected regarding the effects of maintaining or revoking anonymity after transplantation.


Direct Photolithography on Molecular Crystals for High Performance Organic Optoelectronic Devices.
Organic crystals are generated via the bottom-up self-assembly of molecular building blocks which are held together through weak noncovalent interactions. Although they revealed extraordinary charge transport characteristics, their labile nature represents a major drawback toward their integration in optoelectronic devices when the use of sophisticated patterning techniques is required. Here we have devised a radically new method to enable the use of photolithography directly on molecular crystals, with a spatial resolution below 300 nm, thereby allowing the precise wiring up of multiple crystals on demand. Two archetypal organic crystals, i.e., p-type 2,7-diphenyl[1]benzothieno[3,2- b][1]benzothiophene (Dph-BTBT) nanoflakes and n-type N, N'-dioctyl-3,4,9,10-perylenedicarboximide (PTCDI-C8) nanowires, have been exploited as active materials to realize high-performance top-contact organic field-effect transistors (OFETs), inverter and p-n heterojunction photovoltaic devices supported on plastic substrate. The compatibility of our direct photolithography technique with organic molecular crystals is key for exploiting the full potential of organic electronics for sophisticated large-area devices and logic circuitries, thus paving the way toward novel applications in plastic (opto)electronics.


Adhesion of composites to dentin and enamel.
Extrapolations based on the history of the development of composites and an adhesion system for bonding dental resins and composites to hard tooth tissues can rightfully be the basis for strong optimism regarding future improvements in esthetic and conservative treatment modalities. Improved understanding of mechanisms of action and the clinical application steps common to current adhesion systems will certainly lead to improved oral healthcare.


Computerized provider order entry in the emergency department: pilot evaluation of a return on investment analysis instrument.
The Vanderbilt Center for Better Health conducted a workflow analysis study to determine the benefits of implementing a computerized provider order entry system in the adult Emergency Department. Time savings by role was 1619 hours/year for nurses, 815 for medical receptionist, -95 for attendings, and -100 for residents. Translating time savings into bottom line savings (FTE/overtime reduction, additional charges) resulted in $31,424 in time savings and $40,000 cost savings (paper forms).


Accuracy of pedometer steps and time for youth with intellectual disabilities during dynamic movements.
Pedometer accuracy for steps and activity time during dynamic movement for youth with intellectual disabilities (ID) were examined. Twenty-four youth with ID (13 girls, 13.1 +/- 3.2 yrs; 11 boys, 14.7 +/- 2.7 yrs) were videotaped during adapted physical education class while wearing a Walk4Life 2505 pedometer in five locations around the waist. Researchers viewed each videotape and recorded observed steps and activity time. Observed findings were compared with pedometer recorded steps and time. On average, pedometer registered steps were underestimated by approximately 14% +/- 16.5%, whereas pedometer registered time was overestimated by approximately 8.7% +/- 21.8%. The findings indicate that the accuracy of pedometers may be compromised during dynamic movement for youth with ID.


[Occurrence of Planococcus minor Maskell (Hemiptera: Pseudococcidae) in cotton fields of northeast region of Brazil].
The mealybug Planococcus minor Maskell is a significant pest of more than 250 cultivated plants belonging to at least 80 families. Among the host plants several Malvaceae species are attacked, including the genera Gossypium. In 2005 and 2006 the mealybug P. minor was observed infesting cotton fields in the arid area of northeast region of Brazil. The occurrence was registered in high densities and in several farms resulting in mortality of plants in some cases. This species is not cited as a cotton pest in any region of Brazil where cotton grows, although it is enlisted in the Global Pest and Disease Database. Hence, there is a lack of studies what makes this pest of great deal to control.


Genome-wide genetic diversity, population structure and admixture analysis in African and Asian cattle breeds.
Knowledge about genetic diversity and population structure is useful for designing effective strategies to improve the production, management and conservation of farm animal genetic resources. Here, we present a comprehensive genome-wide analysis of genetic diversity, population structure and admixture based on 244 animals sampled from 10 cattle populations in Asia and Africa and genotyped for 69,903 autosomal single-nucleotide polymorphisms (SNPs) mainly derived from the indicine breed. Principal component analysis, STRUCTURE and distance analysis from high-density SNP data clearly revealed that the largest genetic difference occurred between the two domestic lineages (taurine and indicine), whereas Ethiopian cattle populations represent a mosaic of the humped zebu and taurine. Estimation of the genetic influence of zebu and taurine revealed that Ethiopian cattle were characterized by considerable levels of introgression from South Asian zebu, whereas Bangladeshi populations shared very low taurine ancestry. The relationships among Ethiopian cattle populations reflect their history of origin and admixture rather than phenotype-based distinctions. The high within-individual genetic variability observed in Ethiopian cattle represents an untapped opportunity for adaptation to changing environments and for implementation of within-breed genetic improvement schemes. Our results provide a basis for future applications of genome-wide SNP data to exploit the unique genetic makeup of indigenous cattle breeds and to facilitate their improvement and conservation.


Foliar lead uptake by lettuce exposed to atmospheric fallouts.
Metal uptake by plants occurs by soil-root transfer but also by direct transfer of contaminants from the atmosphere to the shoots. This second pathway may be particularly important in kitchen gardens near industrial plants. The mechanisms of foliar uptake of lead by lettuce ( Lactuca sativa ) exposed to the atmospheric fallouts of a lead-recycling plant were studied. After 43 days of exposure, the thoroughly washed leaves contained 335 +/- 50 mg Pb kg(-1) (dry weight). Micro-X-ray fluorescence mappings evidenced Pb-rich spots of a few hundreds of micrometers in diameter located in necrotic zones. These spots were more abundant at the base of the central nervure. Environmental scanning electron microscopy coupled with energy dispersive X-ray microanalysis showed that smaller particles (a few micrometers in diameter) were also present in other regions of the leaves, often located beneath the leaf surface. In addition, submicrometric particles were observed inside stomatal openings. Raman microspectrometry analyses of the leaves identified smelter-originated Pb minerals but also secondary phases likely resulting from the weathering of original particles. On the basis of these observations, several pathways for foliar lead uptake are discussed. A better understanding of these mechanisms may be of interest for risk assessment of population exposure to atmospheric metal contamination.


Head-to-tail cyclization of side chain-protected linear peptides to recapitulate genetically-encoded cyclized peptides.
Genetically-encoded cyclic peptide libraries allow rapid in vivo screens for inhibitors of any target protein of interest. In particular, the Split Intein Circular Ligation of Protein and Peptides (SICLOPPS) system exploits spontaneous protein splicing of inteins to produce intracellular cyclic peptides. A previous SICLOPPS screen against Aurora B kinase, which plays a critical role during chromosome segregation, identified several candidate inhibitors that we sought to recapitulate by chemical synthesis. We describe the syntheses of cyclic peptide hits and analogs via solution-phase macrocyclization of side chain-protected linear peptides obtained from standard solid-phase peptide synthesis. Cyclic peptide targets, including cyclo-[CTWAR], were designed to match both the variable portions and conserved cysteine residue of their genetically-encoded counterparts. Synthetic products were characterized by tandem high-resolution mass spectrometry to analyze a combination of exact mass, isotopic pattern, and collisional dissociation-induced fragmentation pattern. The latter analyses facilitated the distinction between targets and oligomeric side products, and served to confirm peptidic sequences in a manner that can be readily extended to analyses of complex biological samples. This alternative chemical synthesis approach for cyclic peptides allows cost-effective validation and facile chemical elaboration of hit candidates from SICLOPPS screens.


Brain Correlates of the Interaction Between 5-HTTLPR and Psychosocial Stress Mediating Attention Deficit Hyperactivity Disorder Severity.
The serotonin transporter 5-HTTLPR genotype has been found to moderate the effect of stress on severity of attention deficit hyperactivity disorder (ADHD), with stronger effects of stress in carriers of the short allele than in individuals homozygous for the long allele. The underlying neurobiological mechanism of this gene-environment interaction in ADHD is unknown. The authors aimed to determine whether 5-HTTLPR moderates the effect of stress on brain gray matter volume and, if so, which brain regions mediate the effect of this gene-environment interaction on ADHD severity. Structural MRI, 5-HTTLPR genotype, and stress exposure questionnaire data were available for 701 adolescents and young adults participating in the multicenter ADHD cohort NeuroIMAGE study (from 385 families; 291 with ADHD, 78 with subthreshold ADHD, 332 healthy comparison subjects; 55.8% male; average age: 17.0 years). ADHD symptom count was determined through multi-informant questionnaires. For the analysis, a whole-brain voxel-based morphometry approach was combined with mediation analysis. Stress exposure was associated with significantly less gray matter volume in the precentral gyrus, middle and superior frontal gyri, frontal pole, and cingulate gyrus in S-allele carriers compared with participants homozygous for the l-allele. The association of this gene-environment interaction with ADHD symptom count was mediated by gray matter volume in the frontal pole and anterior cingulate gyrus. 5-HTTLPR genotype moderates the effect of stress on brain regions involved in social cognitive processing and cognitive control. Specifically, regions important for cognitive control link this gene-environment interaction to ADHD severity.


Influenza A virus haemagglutinin polymorphism: pleiotropic antigenic variants of A/Shanghai/11/87 (H3N2) virus selected as high yield reassortants.
Genetic reassortment of the A/Shanghai/11/87 (H3N2) variant of influenza A virus with A/PR8/34 (H1N1) virus [the standard donor of high yield (hy) genes for influenza vaccine viruses] resulted in the isolation of two reassortants with differing H3 haemagglutinin (HA) phenotypes, X-99 and X-99a. The two HA phenotypes were derived from individual subpopulations of the H3N2 wild-type virus during the reassortment event. The HA mutants and their respectively derived reassortants (identical in RNA genotype) differed in antigenicity, replication characteristics, yield in chick embryos and haemagglutinin gene sequence. Despite antigenic differences in reactions to polyclonal rabbit antisera of 60%, both X-99 and X-99a, the hy reassortants, were equally immunogenic and protective in BALB/c mice to challenge by parental wild-type virus. Differences in HA phenotype were related to a Ser to Ile change at amino acid position 186. These findings emphasize the polymorphism of influenza virus strains as well as the need for caution in selection of vaccine strains from among antigenically distinct viral subpopulations.


Vitamin D Deficiency and Cardio-Metabolic Risk in a North Indian Community with Highly Prevalent Type 2 Diabetes.
The purpose of this investigation was to examine serum vitamin D status in a population of Punjabi ancestry from Northern India with a high prevalence of type 2 diabetes (T2D) and evaluate the effects of 25(OH)D levels on cardio-metabolic traits. We assessed cardiovascular risk factors and 25(OH)D levels in 1,765 participants (887 T2D cases, 878 normoglycemic controls). 76% of individuals were deficient (<50 nmol/L) in vitamin D. A higher percentage of T2D participants(83%) were vitamin D deficient compared to normoglycemic controls (68%)(p<0.0001).The prevalence of vitamin D deficiency increased progressively with body mass index (BMI) categories (p<0.0001): BMI<23 kg/m2, 65%; BMI 23-27.5 kg/m2, 75%; and BMI>27.5 kg/m2, 81%. T2D participants had significantly decreased serum 25(OH)D levels (β=-0.41, p=2.8 × 10-20). Individuals with low serum 25(OH)D had elevated fasting glucose(β=-0.18, p=0.022), BMI (β=-0.71, p=1.4 × 10-7) and systolic blood pressure (β=-1.68, p=0.006). A positive association of increased 25(OH)D with HOMA-B (β=0.17, p=8.0×10-6), and C-peptide (β=0.09, 0.017) was observed. Non-medicated, normoglycemic, non-hypertensive individuals classified as vitamin D deficient (n=289) exhibited a significant increase in fasting glucose (p=0.02) and BMI (p<0.0001) as well as a significant decrease in C-peptide (p<0.0001) and amylin (p<0.0001) compared to vitamin D sufficient controls (n=150). Vitamin D deficiency appears to be a significant risk factor for T2D severity and associated cardio-metabolic risk. Early intervention may be considered to improve prevention of T2D related cardiovascular complications.


Timing of climate variability and grassland productivity.
Future climates are forecast to include greater precipitation variability and more frequent heat waves, but the degree to which the timing of climate variability impacts ecosystems is uncertain. In a temperate, humid grassland, we examined the seasonal impacts of climate variability on 27 y of grass productivity. Drought and high-intensity precipitation reduced grass productivity only during a 110-d period, whereas high temperatures reduced productivity only during 25 d in July. The effects of drought and heat waves declined over the season and had no detectable impact on grass productivity in August. If these patterns are general across ecosystems, predictions of ecosystem response to climate change will have to account not only for the magnitude of climate variability but also for its timing.


Impaired right ventricular filling in patients with a chronic coronary syndrome.
The prognostic value of right ventricle (RV) systolic dysfunction is known but the RV diastolic dysfunction (RVDD) is less investigated, thus the purpose of this study was to assess the incidence of RVDD in patients with coronary artery disease (CAD) and to identify factors associated with its presence. We examined 200 patients with stable CAD (153 men). RV diastolic parameters were studied by echocardiography: peak velocity of early (Et) and late (At) RV fill-ing and their ratio, velocities at the tricuspid annulus (et', a't, s't). Patients were divided into 2 groups: with (n=92) and without RVDD (n=108). Old myocardial infarction (MI) (p=0.007), anterior MI (p=0.001), congestive heart failure (p=0.030) and peripheral arterial disease (p=0.030) were more prevalent in patients with RVDD. The end-systolic dimensions were higher (p=0.010), while left ventricular (LV) ejection fraction (EF) (p=0.044) and the mitral E/A ratio (p<0.001) were lower in this group. No significant differences were found between the groups in the coronary artery stenosis. Independent predictors of the RVDD presence were increased age, old MI, hyperlipidemia, moderate chronic heart failure, peripheral arterial disease, and decreased LVEF. The RV diastolic dysfunction is much more common than systolic dysfunction in patients with stable CAD (46% and 7.5%, respectively). The RVDD presence was predominantly associated with an increase in age and LV systolic dysfunction, but not with coronary artery lesions. The predictive value of RVDD requires further research.


Evaluation of Residual Diazinon and Chlorpiryfos in Children Herbal Medicines by Headspace-SPME and GC-FID.
The oldest method for the managing of the illness is the use of medicinal plants. The use of herbal products as the first choice in self-treatment of minor conditions continues to expand rapidly across Iran. This makes the safety of herbal products an important public health issue. Pesticides are used widely in agriculture to increase the production by controlling the harmful insects and disease vectors, however it has some hazards on biological system of human especially children. The present study was designed to examine the residual amount of organophosphorus pesticides (Diazinon and Chlorpyrifos) in children herbal medicines available in the Iranian market. Five children herbal medicine liquid dosage forms were purchased from pharmacy store. They were extracted with SPME (Solid Phase Microextraction) using the PDMS-DVB fibre. Then the extracts were injected into a GC. The gas chromatograph was Younglin model YL 6100 equipped with a flame ionization detector. The column was Technokroma 60 m length, 0.53 mm internal diameter and 1.25 µm film coated. The presence and quantity of Diazinon and Chlorpyrifos were evaluated using their standard curves. Trace amounts of chlorpyrifos and diazinon were detected in a few herbal medicines. Based on European pharmacopeia, threshold limits of chlorpyrifos and diazinon residues for medicinal plant materials are 0.2 and 0.5 mg/Kg, respectively. Our analysis results showed that residue limits of these two pesticides in five children herbal medicines are ignorable.


[Experimental kidney transplantation in rats. Technical, functional, and histologic aspects].
In recent years, different experimental transplantation techniques have been developed in animals to gain further insight into the immunologic and non-immunologic processes occurring in grafts. Microsurgery permits the application of these procedures to small animals, as the rat. We present our experience in experimental transplantation in rats, with special reference to isogenic transplantation (inbred animals), leaving solely the graft in the receptor. The technical characteristics, the analytic and histologic findings after transplantation are described.


asb11 is a regulator of embryonic and adult regenerative myogenesis.
The specific molecular determinants that govern progenitor expansion and final compartment size in the myogenic lineage, either during gestation or during regenerative myogenesis, remain largely obscure. Recently, we retrieved d-asb11 from a zebrafish screen designed to identify gene products that are downregulated during embryogenesis upon terminal differentiation and identified it as a potential regulator of compartment size in the ectodermal lineage. A role in mesodermal derivatives remained, however, unexplored. Here we report pan-vertebrate expression of Asb11 in muscle compartments, where it highly specifically localizes to the Pax7(+) muscle satellite cell compartment. Forced expression of d-asb11 impaired terminal differentiation and caused enhanced proliferation in the myogenic progenitor compartment both in in vivo and in vitro model systems. Conversely, introduction of a germline hypomorphic mutation in the zebrafish d-asb11 gene produced premature differentiation of the muscle progenitors and delayed regenerative responses in adult injured muscle. Thus, the expression of d-asb11 is necessary for muscle progenitor expansion, whereas its downregulation marks the onset of terminal differentiation. Hence, we provide evidence that d-asb11 is a principal regulator of embryonic as well as adult regenerative myogenesis.


Physiological and psychosocial age-related changes associated with reduced food intake in older persons.
Dietary intake changes during the course of aging. Normally an increase in food intake is observed around 55 years of age, which is followed by a reduction in food intake in individuals over 65 years of age. This reduction in dietary intake results in lowered levels of body fat and body weight, a phenomenon known as anorexia of aging. Anorexia of aging has a variety of consequences, including a decline in functional status, impaired muscle function, decreased bone mass, micronutrient deficiencies, reduced cognitive functions, increased hospital admission and even premature death. Several changes during lifetime have been implicated to play a role in the reduction in food intake and the development of anorexia of aging. These changes are both physiological, involving peripheral hormones, senses and central brain regulation and non-physiological, with differences in psychological and social factors. In the present review, we will focus on age-related changes in physiological and especially non-physiological factors, that play a role in the age-related changes in food intake and in the etiology of anorexia of aging. At the end we conclude with suggestions for future nutritional research to gain greater understanding of the development of anorexia of aging which could lead to earlier detection and better prevention.


A novel medical image protection scheme using a 3-dimensional chaotic system.
Recently, great concerns have been raised regarding the issue of medical image protection due to the increasing demand for telemedicine services, especially the teleradiology service. To meet this challenge, a novel chaos-based approach is suggested in this paper. To address the security and efficiency problems encountered by many existing permutation-diffusion type image ciphers, the new scheme utilizes a single 3D chaotic system, Chen's chaotic system, for both permutation and diffusion. In the permutation stage, we introduce a novel shuffling mechanism, which shuffles each pixel in the plain image by swapping it with another pixel chosen by two of the three state variables of Chen's chaotic system. The remaining variable is used for quantification of pseudorandom keystream for diffusion. Moreover, the selection of state variables is controlled by plain pixel, which enhances the security against known/chosen-plaintext attack. Thorough experimental tests are carried out and the results indicate that the proposed scheme provides an effective and efficient way for real-time secure medical image transmission over public networks.


[Panniculitis in the setting of visceral leishmaniasis].
A 38-year-old male with a past history of intravenous drug use, AIDS and Visceral Leishmaniasis in 2000, was hospitalized after presenting with fever, myalgias and arthralgias, fatigue, hepatosplenomegaly and oedema of the inferior limbs. On the tenth day of admission, the patient developed painful subcutaneous nodules of the thighs and a Dermatology consultation was requested. A clinical and histological diagnosis of Leishmania Panniculitis was made, in the setting of Visceral Leishmaniasis recurrence. Leishmania Panniculitis is rarely found simultaneously with Visceral Leishmaniasis, and it is more frequently seen in HIV co-infected patients. In this case, the skin involvement allowed for an early diagnosis and histological confirmation of Leishmaniasis recrudescence to be made.


Reflex release of vasopressin and renin in hemorrhage is enhanced by autonomic blockade.
We determined the relationships during hemorrhage between nominal blood volume (BV) and 1) plasma arginine vasopressin (AVP), 2) plasma renin activity (PRA), and 3) mean arterial pressure (MAP). Conscious rabbits were studied under normal conditions and during total autonomic blockade (TAB) at bleeding rates of 2 and 4 ml/min. Normally, MAP was well maintained until BV had been reduced to approximately 65% of control (termed 65% BV) after which it fell abruptly. The threshold for a rise in AVP was 80-75% BV, followed by exponential rises to levels of 14 and 24 times control at the slow and fast rate of bleeding. PRA rose earlier in hemorrhage, but this rise was more gradual, to values at 60% BV of 5.5 and 7 times control at the two rates of bleeding. During TAB, MAP fell rapidly and both BV concentration curves were shifted to the left with the rises in AVP and PRA/unit delta BV greater than normal; at 75% BV at each rate of hemorrhage, AVP and PRA had risen, respectively, to approximately 40 and 8 times control. Normally, the rises in the AVP and PRA (i.e., angiotensin II) concentrations were modest during the nonhypotensive phase, consistent with their minimal constrictor action observed in a parallel study. During the hypotensive phase, both reached high levels in the constrictor range. During TAB, high concentrations were reached with small BV loss, representing a model of near-maximum release of PRA and AVP.


Outer retinal structure in patients with acute zonal occult outer retinopathy.
To correlate visual function with high-resolution images of retinal structure using adaptive optics scanning laser ophthalmoscopy (AOSLO) in 4 patients with acute zonal occult outer retinopathy (AZOOR). Observational case series. Four women, aged 18 to 51, with acute focal loss of visual field or visual acuity, photopsia, and minimal funduscopic changes were studied with best-corrected visual acuity (BCVA), Goldmann kinetic and automated perimetry and fundus-guided microperimetry, full-field and multifocal electroretinography (ffERG and mfERG), spectral-domain optical coherence tomography (SD-OCT), and AOSLO imaging. Cone spacing was measured in 4 eyes and compared with 27 age-similar normal eyes. Additional functional testing in 1 patient suggested that cones were absent but rods remained. Serum from all patients was analyzed for anti-retinal antibody activity. In all patients vision loss was initially progressive, then stable. Symptoms were unilateral in 2 and bilateral but asymmetric in 2 patients. In each patient, loss of retinal function correlated with structural changes in the outer retina. AOSLO showed focal cone loss in most patients, although in 1 patient with central vision loss such change was absent. In another patient, structural and functional analyses suggested that cones had degenerated but rods remained. Anti-retinal antibody activity against a ∼45 kd antigen was detected in 1 of the patients; the other 3 patients showed no evidence of abnormal anti-retinal antibodies. Focal abnormalities of retinal structure correlated with vision loss in patients with AZOOR. High-resolution imaging can localize and demonstrate the extent of outer retinal abnormality in AZOOR patients.


Pertussis epidemiology prior to the introduction of a maternal vaccination program, Queensland Australia.
Pertussis morbidity is highest in infants too young to be fully protected by routine vaccination schedules. Alternate vaccine strategies are required to maximise protection in this age-group. To understand baseline pertussis epidemiology prior to the introduction of the maternal pertussis vaccination program in 2014, we conducted a retrospective case series analyses of 53 901 notifications and temporal trends from 1997 to 2014. Notifications were highest in infants younger than 4 months of age and highest annual notification rates in infants younger than 1 month of age (308/100 000 per year). Amongst Aboriginal and Torres Strait Islander infants aged younger than 1 month, this rate was 576/100 000 per year. Notification rates were 40% higher amongst women 15-44 years, 62·4/100 000 population compared with men (44·5/100 000) and 90% higher in Aboriginal and Torres Strait Islander women of the same age (38·2/100 000) compared with men (19·7/100 000). Six infant deaths were identified, all younger than 2 months of age. Monitoring epidemiology in at-risk groups - infants too young to be vaccinated, women of childbearing age and Aboriginal and Torres Strait Islander peoples - following implementation of the maternal pertussis vaccination program will be important to assess its impact and safety.


Sensitive receptor-specified enzyme-linked immunosorbent assay for Escherichia coli verocytotoxin.
The specific identification of verocytotoxin (VT)-producing Escherichia coli (VTEC) requires the detection of VTs in bacterial culture filtrates or the detection of genes encoding these toxins in bacterial cells by specific DNA probes. The standard method for detecting these toxins involves a time-consuming, labor-intensive, and expensive cytotoxicity assay. We have developed a specific, highly sensitive receptor-specified enzyme-linked immunosorbent assay (RELISA) to detect VT1, one of at least two VTs implicated in human disease. The assay is based on the affinity of VT1 for the glycolipid globotriosyl ceramide (Gb3). Gb3 was de-N-acylated to yield lyso-Gb3, which is more polar but retains VT1 binding. Lyso-Gb3 was used to sensitize microdilution plates to bind VT1 for subsequent immunodetection. This RELISA was used to detect VT1 in the culture supernatant of a variety of bacteria of known VT status. The assay was compared with the highly sensitive cell cytotoxicity assay for their abilities to detect VT. The RELISA was as sensitive as the cytotoxicity assay and, in a blind study, 100% specific. This assay will provide a quick, specific, efficient adjunct to the diagnosis and epidemiological study of VTEC infections and their relationship to human disease.


Both soluble guanylate cyclase and particulate guanylate cyclase regulate myometrial contractility.
Our purpose was to compare the effects of agents stimulating particulate and soluble guanylate cyclase with spontaneous rat uterine contractions at midgestation and term. Uterine rings from midgestation (day 13) and term nonlaboring (day 22) rats were positioned in organ chambers for isometric force recording. Rings were treated with increasing concentrations of atrial natriuretic peptide, permeable analogs of cyclic guanosine monophosphate, and diethylamine/nitric oxide. Atrial natriuretic peptide was more effective in inhibition of uterine contractions than diethylamine/nitric oxide. The 50% inhibitory concentrations were -7.4 +/- 0.12 and -7.38 +/- 0.11 for atrial natriuretic peptide and -5.68 +/- 0.09 and -4.23 +/- 0.12 for diethylamine/nitric oxide at midgestation and term, respectively. Pretreatment of uterine rings with atrial natriuretic peptide significantly attenuated inhibition of spontaneous contractions by diethylamine/nitric oxide at midgestation. Uterine spontaneous contractions are influenced by both soluble and particulate guanylate cyclase; the former, but not latter, is gestational age dependent.


[Multielectronic computerized EMG: technical notes on the recording and parallel off-line elaboration].
A Multielectrodic EMG analysis program is developing. The purpose is to get as short as possible the main EMG parameters (amplitude, duration, frequency) of most motor units, and to reach an estimation of the anatomical extent of single units. According to the muscle extent a variable number of electrodes are inserted crosswise the fibers. EMG signals are simultaneously recorded on a multichannel AMPEX FR1300 and then off-line processed by a 21MX HP minicomputer connected with a 5Mbytes disc drive. Some technical problems had to be solved:channel amplification adjustment to avoid any difference among preamplifiers calibration and filtering, severe hum filtering of main power that is specially strong in nultielectrodic recording systems, the need of sampling at the same Nyquist time the signals of different channels. The computer is instructed to identify the "sinchronous" units i.e. the motor units recorded from more than one channel. These motor units are detected, counted and deleted from all the channels, except the one where they show the maximum amplitude. The percentage of these sinchronous units depends upon the interelectrodic distance and their anatomical area, thus it can support an evaluation of motor unit anatomical spread.


Thrombus-Targeted Theranostic Microbubbles: A New Technology towards Concurrent Rapid Ultrasound Diagnosis and Bleeding-free Fibrinolytic Treatment of Thrombosis.
Myocardial infarction and stroke are leading causes of morbidity/mortality. The typical underlying pathology is the formation of thrombi/emboli and subsequent vessel occlusion. Systemically administered fibrinolytic drugs are the most effective pharmacological therapy. However, bleeding complications are relatively common and this risk as such limits their broader use. Furthermore, a rapid non-invasive imaging technology is not available. Thereby, many thrombotic events are missed or only diagnosed when ischemic damage has already occurred. Design and preclinical testing of a novel 'theranostic' technology for the rapid non-invasive diagnosis and effective, bleeding-free treatment of thrombosis. A newly created, innovative theranostic microbubble combines a recombinant fibrinolytic drug, an echo-enhancing microbubble and a recombinant thrombus-targeting device in form of an activated-platelet-specific single-chain antibody. After initial in vitro proof of functionality, we tested this theranostic microbubble both in ultrasound imaging and thrombolytic therapy using a mouse model of ferric-chloride-induced thrombosis in the carotid artery. We demonstrate the reliable highly sensitive detection of in vivo thrombi and the ability to monitor their size changes in real time. Furthermore, these theranostic microbubbles proofed to be as effective in thrombolysis as commercial urokinase but without the prolongation of bleeding time as seen with urokinase. We describe a novel theranostic technology enabling simultaneous diagnosis and treatment of thrombosis, as well as monitoring of success or failure of thrombolysis. This technology holds promise for major progress in rapid diagnosis and bleeding-free thrombolysis thereby potentially preventing the often devastating consequences of thrombotic disease in many patients.


Gene regulation in Kluyveromyces marxianus in the context of chromosomes.
Eukaryotes, including the unicellular eukaryotes such as yeasts, employ multiple levels of gene regulation. Regulation of chromatin structure through chromatin compaction cascades, and influenced by transcriptional insulators, might play a role in the coordinated regulation of genes situated at adjacent loci and expressed as a co-regulated cluster. Subtelomeric gene silencing, which has previously been described in the yeast Saccharomyces cerevisiae, is an example of this phenomenon. Transcription from a common regulatory element located around a shared intergenic region is another factor that could coordinate the transcription of genes at adjacent loci. Additionally, the presence of DNA binding sites for the same transcription factor may coordinate expression of multiple genes. Yeasts such as the industrially important Kluyveromyces marxianus may also display these modes of regulation, but this has not been explored to date. An exploration was done using a complete genome and RNA-seq data from a previous study of the transcriptional response to glucose or xylose as the carbon source in a defined culture medium, and investigating whether the species displays clusters of co-localised differentially expressed genes. Regions of possible subtelomeric silencing were evident, but were non-responsive to the carbon sources tested here. Additionally, glucose or xylose responsive clusters were discovered far from telomeres which contained some of the most significantly differentially expressed genes, encoding enzymes involved in the utilisation of alternative carbon sources such as the industrially important inulinase gene INU1. These clusters contained putative binding sites for the carbon source responsive transcription factors Mig1 and Adr1. Additionally, we investigated the potential contribution of common intergenic regions in co-regulation. Some observations were also made in terms of the evolutionary conservation of these clusters among yeast species and the presence of potential transcriptional insulators at the periphery of these clusters.


Silicon-Copper Helical Arrays for New Generation Lithium Ion Batteries.
The helical array (with 10 atom % Cu) exhibits 3130 mAh g(-1) with 83% columbic efficiency and retains 83% of its initial discharge capacity after 100th cycle. Homogeneously distributed interspaces between the helical arrays accommodate high volumetric changes upon cycling and copper atoms form a conductive network to buffer the mechanical stress generated in the electrode while minimizing electrochemical agglomeration of Si. Also, ion assistance is believed to enhance the density of the helices at the bottom thus increasing the adhesion.


Measuring Stroke Quality: Methodological Considerations in Selecting, Defining, and Analyzing Quality Measures.
Knowledge about stroke and its management is growing rapidly and stroke systems of care must adapt to deliver evidence-based care. Quality improvement initiatives are essential for translating knowledge from clinical trials and recommendations in guidelines into routine clinical practice. This review focuses on issues central to the measurement of the quality of stroke care, including selection and definition of quality measures, identification of the eligible patient cohorts, optimization of data quality, and considerations for data analysis and interpretation.


Gastric function and obesity: gastric emptying, gastric acid secretion, and plasma pepsinogen.
Because rapid gastric emptying and a shortened satiety period might contribute to development of obesity, this study compared gastric emptying of acaloric liquid, gastric acid production, and plasma levels of gastrin and pepsinogen I (PG I) and II (PG II) among obese and nonobese Pima Indians. Rates of fractional gastric emptying and of gastric acid secretion were similar in the two groups, basally and after an acaloric liquid meal. Basal and postprandial plasma gastrin levels did not differ significantly in obese and nonobese Pimas , but peak betazole-stimulated gastric acid output was greater in the obese group, except when normalized by body weight. The plasma PG I and PG II concentrations and PG I/PG II ratio did not differ significantly between the two groups, but the PG I/PG II ratio had a positive correlation with peak acid output. No correlation was found between fractional gastric emptying rate and degree of obesity. We conclude that an increased gastric emptying rate for liquid does not contribute to the pathogenesis of obesity in Pima Indians.


Overestimation of hemoglobin in a patient with an IgA-kappa monoclonal gammopathy.
A patient with multiple myeloma had an automated blood count performed on a Coulter STK-S counter that repeatedly failed internal limits for both mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. The calculated hematocrit agreed with a spun hematocrit, suggesting that the hemoglobin concentration was being overestimated by the automated counter. Measurement of the plasma hemoglobin concentration of the sample, which showed no visible hemolysis, gave a hemoglobin concentration of 32 g/L on the STK-S analyzer. Correction of the whole blood hemoglobin using the plasma hemoglobin gave a value consistent with the hematocrit. The corrected mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration values were within standard limits. This patient's paraprotein was characterized as IgA-kappa and was present at a concentration of 61 g/L. The hemoglobin concentration measured on whole blood by Sysmex NE 8000 and Technicon H*1E autoanalyzers agreed reasonably well with the corrected result from the STK-S.


Endometrial rollerball ablation.
To study a standardized technique for endometrial rollerball ablation and various methods of preoperative preparation. All patients had refractory symptomatic menorrhagia and previously failed conservative surgery and other forms of medical therapy, such as progestogens. Patients received a preoperative regimen of either leuprolide acetate, danazol, Nolvadex or Depo-Provera. They then underwent hysteroscopically controlled rollerball ablation at 80-100 W with 1.5% glycine as the distending medium. The endometrium was evaluated hysteroscopically and considered to be completely atrophic, intermediate or no response. Refractory symptomatic menorrhagia was treated successfully in 38 of 40 patients. Nineteen reported amenorrhea; the other 21 reported subjective and objective improvement of bleeding. Three patients, despite improvements in flow, were unhappy with the overall result. Two did not wish repeat ablation and subsequently underwent vaginal hysterectomy. The third underwent repeat ablation and became amenorrheic. The ability to achieve complete endometrial atrophy prior to ablation was improved with leuprolide acetate (19/24) and danazol (5/6) when compared to tamoxifen (0/4) and Depo-Provera (0/6). Attainment of amenorrhea after ablation was significantly improved when complete atrophy (19/24) was achieved prior to ablation as compared to the ability to achieve amenorrhea when no endometrial response was achieved (0/7). The only significant complication was one uterine perforation in a patient undergoing repeat ablation. Endometrial rollerball ablation is a safe, effective means of controlling refractory menorrhagia. Amenorrhea is best attained when complete preoperative atrophy is achieved. Leuprolide and danazol were superior to tamoxifen and Depo-Provera.


Contour integration deficits in anisometropic amblyopia.
Previous retrospective studies have found that integration of orientation information along contours defined by Gabor patches is abnormal in strabismic, but not in anisometropic, amblyopia. This study was conducted to reexamine the question of whether anisometropic amblyopes have contour integration deficits prospectively in an untreated sample, to isolate the effects of the disease from the effects of prior treatment-factors that may have confounded the results in previous retrospective studies. Contour detection thresholds, optotype acuity, and stereoacuity were measured in a group of 19 newly diagnosed anisometropic amblyopes before initiation of occlusion therapy. Contour detection thresholds were measured using a card-based procedure. Significant interocular differences in contour detection thresholds were present in 14 of the 19 patients with anisometropic amblyopia. Contour integration deficits are a common, but not universal, finding in untreated anisometropic amblyopia. Differences in the prevalence of contour integration deficits between the present study and that of another study may lie in differences in treatment history and/or in the sensitivity of the two different contour integration tasks.


Is magnetic topology important for heating the solar atmosphere?
Magnetic fields permeate the entire solar atmosphere weaving an extremely complex pattern on both local and global scales. In order to understand the nature of this tangled web of magnetic fields, its magnetic skeleton, which forms the boundaries between topologically distinct flux domains, may be determined. The magnetic skeleton consists of null points, separatrix surfaces, spines and separators. The skeleton is often used to clearly visualize key elements of the magnetic configuration, but parts of the skeleton are also locations where currents and waves may collect and dissipate. In this review, the nature of the magnetic skeleton on both global and local scales, over solar cycle time scales, is explained. The behaviour of wave pulses in the vicinity of both nulls and separators is discussed and so too is the formation of current layers and reconnection at the same features. Each of these processes leads to heating of the solar atmosphere, but collectively do they provide enough heat, spread over a wide enough area, to explain the energy losses throughout the solar atmosphere? Here, we consider this question for the three different solar regions: active regions, open-field regions and the quiet Sun. We find that the heating of active regions and open-field regions is highly unlikely to be due to reconnection or wave dissipation at topological features, but it is possible that these may play a role in the heating of the quiet Sun. In active regions, the absence of a complex topology may play an important role in allowing large energies to build up and then, subsequently, be explosively released in the form of a solar flare. Additionally, knowledge of the intricate boundaries of open-field regions (which the magnetic skeleton provides) could be very important in determining the main acceleration mechanism(s) of the solar wind.


Emergency department extracorporeal membrane oxygenation may also include noncardiac arrest patients
The primary purpose of this study is to report the experience on the extracorporeal membrane oxygenation (ECMO) process for patients in the critical care unit (CCU) of an emergency department of a tertiary hospital in Turkey, from cannulation to decannulation, including follow-up procedures. This retrospective and observational study included eight patients who received ECMO from January 2018 to January 2020. We evaluated the demographics, indications for ECMO, laboratory values, Respiratory ECMO Survival Prediction, Survival After Veno-Arterial ECMO and ECMO net scores, the management process, and patient outcomes. Blood gas analyses done after the first hour of ECMO initiation and the reevaluation of the patients' Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores in the 24th hour of ECMO were recorded. The mean age was 52.7 ± 14.2 years. The median duration of the ECMO run was 81 (min–max: 4–267) h, and the mean length of CCU stay was 10.2 ± 6.7 days. Of the 8 patients studied, 5 (62.5%) had veno-arterial and 3 (37.5%) had veno-venous ECMO. Three patients were successfully weaned (37.5%). The overall survival-to-discharge rate was 25%. Carbon dioxide levels were significantly decreased 1 h after ECMO initiation (P = 0.038) as well as the need for vasopressors. Lactate levels were lower in decannulated patients. Changes in the APACHE II score were more consistent with the clinical deterioration in patients than SOFA score changes were. In the early phase of ECMO, vital signs improve, and the need for vasopressors and carbon dioxide levels decrease. Thus, CCUs in Emergency Departments with ECMO capabilities could potentially be designed, and emergency department ECMO algorithms could be tailored for critically ill patients in addition to out-of-hospital cardiac arrest patients.


The third molar as an age marker in adolescents: new approach to age evaluation.
Adolescence is a relatively short period between childhood and adulthood. It is very difficult to determine adulthood based on biological indicators. The third molar may be considered a potential age marker for the period between the ages of 16-21. Our study evaluated a set of 1700 panoramic radiographs of individuals aged between 5 and 21 years. Results confirmed the statistically significant difference in the course of third molars development. The mean deviation for individuals with one third molar agenesis is -0.98 years, for individuals with two third molars agenesis -1.89 years, and with three molars agenesis -3.28 years. Thus, the extent of the deviation is directly proportional to the number of unformed third molars. The calculation of age according to the mean of stages of all third molars could lead to the underestimation of age. No intergender differences were found. Age determination using third molars could be used for forensic purposes.


Bayesian networks in environmental and resource management.
This overview article for the special series, "Bayesian Networks in Environmental and Resource Management," reviews 7 case study articles with the aim to compare Bayesian network (BN) applications to different environmental and resource management problems from around the world. The article discusses advances in the last decade in the use of BNs as applied to environmental and resource management. We highlight progress in computational methods, best-practices for model design and model communication. We review several research challenges to the use of BNs in environmental and resource management that we think may find a solution in the near future with further research attention.


Retroviral-associated eosinophilic leukemia in the cat.
Fourteen specific-pathogen-free cats were inoculated with a putative env gene recombinant feline retrovirus, PR8. An isolate of the Rickard strain of feline leukemia virus (FeLV-R), PR8, has the properties of both an exogenous (FeLV-R) and an endogenous (xenotropic) feline retrovirus (RD-114). Twelve of the PR8-inoculated cats developed viremia; 2 of the 12 cats developed eosinophilia, with 1 being diagnosed with eosinophilic leukemia and the other with extreme eosinophilic hyperplasia. Eosinophilic leukemia is rare in cats and has not previously been associated with retroviral infection. Changes in the viral envelope properties may have altered the pathogenicity of the exogenous virus to cause this rare form of leukemia.


Intracranial Pure Germinoma With Optic Nerve Infiltration.
A 19-year-old man presented with a 3-year history of episodic headaches, right hemiparesis, and progressive vision loss in both eyes. Initially, extensive laboratory testing was unrevealing. MRI later demonstrated progressive enlargement and enhancement of the left optic nerve poorly correlated with the timing of his clinical manifestations. There was no clinical or radiological response to treatment with corticosteroids, mycophenolate mofetil, or rituximab administered empirically for possible inflammatory processes. Later in the disease course, he developed diabetes insipidus (DI), worsening vision to light perception bilaterally, severe cognitive decline, and spastic quadriparesis. Cerebrospinal fluid (CSF) beta human chorionic gonadotropin (β-hCG) was elevated. Eventually, a left optic nerve biopsy was performed, which was consistent with an intracranial pure germinoma with infiltration of the optic nerve and disseminated leptomeningeal disease. Although rare, intracranial germ cell tumors can primarily involve the anterior visual pathways and should be considered in the setting of DI and elevated CSF β-hCG.


Rab14 from Bombyx mori (Lepidoptera: Bombycidae) shows ATPase activity.
Rab GTPases are essential for vesicular transport, whereas adenosine triphosphate (ATP) is the most important and versatile of the activated carriers in the cell. But there are little reports to clarify the connection between ATP and Rab GTPases. A cDNA clone (Rab14) from Bombyx mori was expressed in Escherichia coli as a glutathione S-transferase fusion protein and purified. The protein bound to [(3)H]-GDP and [(35)S]-GTPgammaS. Binding of [(35)S]-GTPgammaS was inhibited by guanosine diphosphate (GDP), guanosine triphosphate (GTP) and ATP. Rab14 showed GTP- and ATP-hydrolysis activity. The Km value of Rab14 for ATP was lower than that for GTP. Human Rab14 also showed an ATPase activity. Furthermore, bound [(3)H]-GDP was exchanged efficiently with GTP and ATP. These results suggest that Rab14 is an ATPase as well as GTPase and gives Rab14 an exciting integrative function between cell metabolic status and membrane trafficking.


Oxidative stress in Alzheimer patients in different stages of the disease.
Increasing evidence demonstrates that oxidative stress causes damage to cell function with aging and is involved in a number of age-related disorders including atherosclerosis, arthritis, and neurodegenerative disorders. Cellular changes show that oxidative stress is a condition that precedes the appearance of the hallmark pathologies of the disease, neurofibrillary tangles and senile plaques. The aim of this article is to analyze the different biomarkers of oxidative stress in Alzheimer patients, in different stages of the illness, and compare the results with a control group. A nutritional evaluation was carried out, including anthropometric and biological measures and a 3 day dietary record. The concentration of substances which react to thiobarbituric acid (TBARS) was measured as a marker of the degree of peroxidation using the HPLC method. The oxidation of proteins was analyzed by measuring the carbonyl groups in plasma. In addition, measurements were made of the total antioxidant activity in plasma and the activity of endogenous antioxidant enzymes such as gluthatione peroxidase, gluthatione reductase and superoxide dismutase. The total antioxidant plasmatic status of the patients with Alzheimer both in light-moderate phase and in advanced phase was lower than in the control. No significant differences were observed between the different stages of the disease in protein oxidation levels. Peroxidation was higher in patients in the advanced stage of the disease than in the control group. However, no significant differences were observed between the different stages of the disease. In this preliminary study, it was observed that Alzheimer patients in the light-moderate stage already present oxidative stress levels above those of the control group.


Esophageal eosinophilia after radiofrequency ablation for Barrett's esophagus.
Radiofrequency ablation (RFA) with HALO system has been developed as a new treatment option for Barrett's esophagus (BE). It had been observed that some patients had esophageal eosinophilia (EE) infiltration after RFA. The incidence and features of EE after RFA were systematically determined. From a prospectively compiled database, data on 148 patients who underwent RFA for BE were analyzed. Biopsies were taken pre- and post-RFA from the BE segment, and histological sections of the biopsy specimens were stained with hematoxylin and eosin, and examined by a gastrointestinal pathologist. The incidence of EE post-RFA was then determined. Of the 148 patients, 120 (81%) were men, 137 (92%) were white, 64 (43%) were overweight and 49 (33%) obese, and 128 (86%) were over 50 years of age or more. Four (2.7%) of the patients developed post-RFA EE, but none had symptoms of eosinophilic esophagitis. All patients except one had a history of seasonal allergies. All four were taking proton pump inhibitor before and after RFA. Two patients with EE drank alcohol, one of which was a smoker. EE is a potential adverse event of RFA for BE. The absence of esophageal dysfunction symptoms suggests a different clinicopathological entity from eosinophilic esophagitis. Further studies should be done to assess its clinical significance, if therapy is needed, or if it may eventually lead to eosinophilic esophagitis.


Emerging negative Atlantic Multidecadal Oscillation index in spite of warm subtropics.
Sea surface temperatures in the northern North Atlantic have shown a marked decrease over the past several years. The sea surface in the subpolar gyre is now as cold as it was during the last cold phase of the Atlantic Multidecadal Oscillation index in the 1990s. This climate index is associated with shifts in hurricane activity, rainfall patterns and intensity, and changes in fish populations. However, unlike the last cold period in the Atlantic, the spatial pattern of sea surface temperature anomalies in the Atlantic is not uniformly cool, but instead has anomalously cold temperatures in the subpolar gyre, warm temperatures in the subtropics and cool anomalies over the tropics. The tripole pattern of anomalies has increased the subpolar to subtropical meridional gradient in SSTs, which are not represented by the AMO index value, but which may lead to increased atmospheric baroclinicity and storminess. Here we show that the recent Atlantic cooling is likely to persist, as predicted by a statistical forecast of subsurface ocean temperatures and consistent with the irreversible nature of watermass changes involved in the recent cooling of the subpolar gyre.


What factors are associated with physical activity in older people, assessed objectively by accelerometry?
To assess physical activity (PA) levels measured objectively using accelerometers in community-dwelling older people and to examine the associations with health, disability, anthropometric measures and psychosocial factors. Cross-sectional survey. Single general practice (primary care centre), United Kingdom. Random selection of 560 community-dwelling older people at least 65 years old, registered with the practice. 43% (238/560) participated. Participants completed a questionnaire assessing health, disability, psychosocial factors and PA levels; underwent anthropometric assessment; and wore an accelerometer (Actigraph) for 7 days. Average daily accelerometer step-counts and time spent in different PA levels. Associations between step-counts and other factors were examined using linear regression. Average daily step-count was 6443 (95% CI 6032 to 6853). Men achieved 754 (84 to 1424) more steps daily than women. Step-count declined steadily with age. Independent predictors of average daily step-count were: age; general health; disability; diabetes; body mass index; exercise self-efficacy; and perceived exercise control. Activities associated independently with higher step-counts included number of long walks and dog-walking. Only 2.5% (6/238) of participants achieved the recommended 150 minutes weekly of at least moderate-intensity activity in > or = 10 minute bouts; 62% (147/238) achieved none. This is the first population-based sample of older people with objective PA and anthropometric measures. PA levels in older people are well below recommended levels, emphasising the need to increase PA in this age group, particularly in those who are overweight/obese or have diabetes. The independent effects of exercise self-efficacy and exercise control on PA levels highlight their role as potential mediators for intervention studies.


Twofold C-H Activation-Based Enantio- and Diastereoselective C-H Arylation Using Diarylacetylenes as Rare Arylating Reagents.
C-H bond activation has been established as an attractive strategy to access axially chiral biaryls, and the most straightforward method is direct C-H arylation of arenes. However, the arylating source has been limited to several classes of reactive and bulky reagents. Reported herein is rhodium-catalyzed 1:2 coupling of diarylphosphinic amides and diarylacetylenes for enantio- and diastereoselective construction of biaryls with both central and axial chirality. This twofold C-H activation reaction stays contrast to the previously explored Miura-Satoh type 1:2 coupling of arenes and alkynes in terms of chemoselectivity and proceeded under mild conditions with the alkyne acting as a rare arylating reagent. Both C-H activation events are stereo-determining and are under catalyst control, with the 2nd C-H activation being diastereo-determining in a remote fashion. Analysis of the stereochemistry of the major and side products suggests moderate enantioselectivity of the initial C-H activation-desymmetrization process. However, the minor (R) rhodium vinyl intermediate is consumed more readily in undesired protonolysis, eventually resulting in high enantio- and diastereoselectivity of the major product.


Deciphering the molecular landscape in chronic lymphocytic leukemia: time frame of disease evolution.
Dramatic advances in next generation sequencing technologies have provided a novel opportunity to understand the molecular genetics of chronic lymphocytic leukemia through the comprehensive detection of genetic lesions. While progress is being made in elucidating the clinical significance of recurrently mutated genes, layers of complexity have been added to our understanding of chronic lymphocytic leukemia pathogenesis in the guise of the molecular evolution and (sub)clonal architecture of the disease. As we prepare for an era of tailored therapy, we need to appreciate not only the effect mutations have on drug response but also the impact subclones containing specific mutations have at initial presentation, during therapy and upon relapse. Therefore, although the wealth of emerging genetic data has great potential in helping us devise strategies to improve the therapy and prognosis of patients, focused efforts will be required to follow disease evolution, particularly in the context of novel therapies, in order to translate this knowledge into clinical settings.


[Experimental candidiasis of the digestive organs in newborn animals].
Morphogenesis of alimentary tract candidosis was studied in the experimental neonate model. The infection was characterized by rapid progression, multiorgan involvement and weak cellular responses. Most commonly the oral cavity and esophagus were the sites of superficial lesions, while the stomach of deep ones. The penetration of the mucous membrane by fungal elements and the vascular invasion resulted in some cases in hematogenous dissemination of the infection.


Circadian regulation of appetite and time restricted feeding.
The circadian system plays an important role in the temporal regulation of metabolic processes as well as food intake to ensure energy efficiency. The 'master' clock is located within the superchiasmatic nucleus and receives input from the retina so that it can be entrained by the light:dark cycle. In turn, the master clock entrains other clocks in the central nervous system, including areas involved in energy homeostasis such as the arcuate nucleus, and the periphery (e.g. adipose tissue and the gastrointestinal tract). This master clock is reinforced by other zeitgebers such as the timing of food intake and activity. If these zeitgebers desynchronise, such as occurs in high fat diet-induced obesity or shift work conditions, it can lead to a misalignment of circadian clocks, disruption of metabolic processes and the development of metabolic disorders. The timing of food intake is a strong zeitgeber, particularly in the gastrointestinal tract, and therefore time restricted feeding offers potential for the treatment of diet and shift work induced metabolic disorders. This review will focus on the role of the circadian system in food intake regulation and the effect of environment factors, such as high fat diet feeding or shift work, on the temporal regulation of food intake along with the benefits of time restricted feeding.


Experimental demonstration of eight-wavelength distributed feedback semiconductor laser array using equivalent phase shift.
An eight-wavelength distributed feedback semiconductor laser array with λ/4 equivalent phase shift based on reconstruction-equivalent-chirp technique was demonstrated. It shows very good linearity in lasing wavelengths with its deviation from -0.22 to 0.20 nm. The threshold currents are between 19 and 24 mA. The side-mode suppression ratios are all larger than 40 dB under the bias currents of 70 mA. The slope efficiencies at room temperature are all about 0.4 W/A. The grating was fabricated only by common holographic exposure and an additional micrometer-level conventional photolithography, which results in a low cost.