Transmission of insect-vectored pathogens: effects of vector fitness as a function of infectivity status.
The transmission of insect-vectored pathogens is dependent on the population dynamics of the vector. Epidemiological models typically assume that birth and death rates of pathogen-free and inoculative vectors are equal, an assumption that is not true for all pathosystems. Here, a series of simple and general epidemiological models were used to explore how assumptions about birth and death rates of vectors based on their infectivity status influence disease incidence. With fixed death rate of pathogen-free vectors, increasing the death rate of inoculative vectors reduced vector density, the proportion of vectors that were inoculative, and the proportion of hosts infected. This effect was mediated by acquisition rate. Specifically, increasing the acquisition rate increased the proportion of vectors that were inoculative, thereby increasing the proportion of the vector population that experienced the increased death rate. With fixed birth rate of pathogen-free vectors, variation in birth rate of inoculative vectors had little influence on disease incidence provided that the birth rate of pathogen-free vectors was much greater than their death rate. However, when the birth rate of pathogen-free vectors was only slightly greater than their death rate, large increases in the birth rate of inoculative vectors increased total vector density and disease incidence. The results indicate that assumptions about birth and death rates of vectors based on infectivity status can have important effects on the vector population that in turn affects disease incidence.


Toward Enhanced Electrochemical Performance by Investigation of the Electrochemical Reconstruction Mechanism in Co2V2O7 Hexagonal Nanosheets for Hybrid Supercapacitors.
As for hybrid supercapacitors, it is important to enhance the long cycling performance and high specific capacitance. In this paper, cobalt vanadate (Co2V2O7) hexagonal nanosheets on nickel foam are manufactured by a facile hydrothermal method and then transformed into numerous smaller size interconnected hierarchical nanosheets without any shape change via electrochemical reconstruction. Benefiting from the favorable architecture of hierarchical nanosheets via electrochemical reconstruction, the Co2V2O7 hexagonal nanosheet electrode exhibits a remarkable long cycling performance with 272% specific capacitance retention after 100,000 cycles at a current density of 5 A g-1 and then displays an increasing specific capacitance of 1834 F g-1 (tested at 1 A g-1). Furthermore, an aqueous hybrid supercapacitor device based on the Co2V2O7 hexagonal nanosheet electrode exhibits a high energy density of 35.2 Wh kg-1 at a power density of 1.01 kW kg-1 and an excellent cyclic stability with 71.4% capacitance retention after 10,000 cycles at 5 A g-1. These results offer a practicable pathway for enhancing the electrochemical properties of other metal oxides through electrochemical reconstruction.


Analytic Gravitational Waveforms for Generic Precessing Binary Inspirals.
Binary systems of two compact objects circularize and spiral toward each other via the emission of gravitational waves. The coupling of the spins of each object with the orbital angular momentum causes the orbital plane to precess, which leads to modulation of the gravitational wave signal. Until now, generating frequency-domain waveforms for fully precessing systems for use in gravitational wave data analysis meant numerically integrating the equations of motion, then Fourier transforming the result, which is very computationally intensive for systems that complete hundreds or thousands of cycles in the sensitive band of a detector. Previously, analytic solutions were only available for certain special cases or for simplified models. Here we describe the construction of closed-form, frequency-domain waveforms for fully precessing, quasicircular binary inspirals.


Fate of sudden deafness occurring in the only hearing ear: outcomes and timing to consider cochlear implantation.
The present study was undertaken to learn the outcome of patients with idiopathic sudden sensorineural hearing loss (ISSNHL) in their only hearing ear. Timing to conduct a cochlear implantation was also determined in those who did not recover the hearing. The study group comprised 25 patients who confronted ISSNHL in their only hearing ear. A total of 192 patients, who had ISSNHL in one ear and had normal contralateral ear, served as the control. Demographically there were no significant differences between the groups. The recovery rate was similar between the groups: 64.0% in the experimental and 62.5% in the control group. The duration until the recovery of ISSNHL in the only hearing ear was 5-90 days (average 17.6 days). In the experimental group, 8 patients did not recover from ISSNHL, and underwent cochlear implantation in 6 with satisfactory results. These results suggest that the same treatment is applicable for patients with ISSNHL regardless of whether their contralateral ear is deaf or normal. For those who do not recover from ISSNHL in their only hearing ear, culminating in bilateral deafness, we may consider further definitive treatment including cochlear implantation as early as 3 months after initiating the treatment of ISSNHL.


Medicare prescription drug coverage: consumer information and preferences.
We investigate prescription drug use, and information and enrollment intentions for the new Medicare Part D drug insurance program, using a sample of Medicare-eligible subjects surveyed before open enrollment began for this program. We find that, despite the complexity of competing plans offered by private insurers under Part D, a majority of the Medicare population had information on this program and a substantial majority planned to enroll. We find that virtually all elderly, even those with no current prescription drug use, can expect to benefit from enrollment in a Part D Standard plan at the low premiums available in the current market. However, there is a significant risk that many eligible seniors, particularly low-income elderly with poor health or cognitive impairment, will make poor enrollment and plan choices.


Developing and piloting a context-specified ethics framework for health technology assessment: the South African Values and Ethics for Universal Health Coverage approach.
While ethics has been identified as a core component of health technology assessment (HTA), there are few examples of practical, systematic inclusion of ethics analysis in HTA. Some attribute the scarcity of ethics analysis in HTA to debates about appropriate methodology and the need for ethics frameworks that are relevant to local social values. The "South African Values and Ethics for Universal Health Coverage" (SAVE-UHC) project models an approach that countries can use to develop HTA ethics frameworks that are specific to their national contexts. The SAVE-UHC approach consisted of two phases. In Phase I, the research team convened and facilitated a national multistakeholder working group to develop a provisional ethics framework through a collaborative, engagement-driven process. In Phase II, the research team refined the model framework by piloting it through three simulated HTA appraisal committee meetings. Each simulated committee reviewed two case studies of sample health interventions: opioid substitution therapy and either a novel contraceptive implant or seasonal influenza immunization for children under five. The methodology was fit-for-purpose, resulting in a context-specified ethics framework and producing relevant findings to inform application of the framework for the given HTA context. The SAVE-UHC approach provides a model for developing, piloting, and refining an ethics framework for health priority-setting that is responsive to national social values. This approach also helps identify key facilitators and challenges for integrating ethics analysis into HTA processes.


Effects of granulocyte colony-stimulating factor administration to periparturient cows on neutrophils and bacterial shedding.
Administration of recombinant bovine granulocyte colony stimulatory factor to periparturient dairy cows was evaluated as a method to prevent periparturient immunosuppression. Eleven of 21 cows were experimentally infected with Staphylococcus aureus in one mammary quarter prior to the study. Cows were randomly assigned to four groups in a 2 x 2 factorial design to evaluate the effects of placebo or recombinant bovine granulocyte colony stimulatory factor administration on chronic, subclinically infected and uninfected cows during the periparturient period. Blood neutrophils were isolated and evaluated for phagocytic activities 5 wk before expected parturition through 7 wk postpartum. Administration of recombinant bovine granulocyte colony stimulatory factor (5 micrograms/kg body weight or placebo subcutaneously beginning 14 d prepartum through 10 d post-partum) resulted in a prepartum and postpartum leukocytosis of 35,600/microliters and 53,500/microliters, respectively. This was attributed to a mature neutrophilia of 24,010/microliters during prepartum and 38,080/microliters during postpartum treatment periods (pretreatment baseline = 2330/microliters). Mononuclear cell counts averaged 7610/microliters during prepartum and 9830/microliters during postpartum treatment periods (baseline = 3450/microliters). Neutrophil random and directed migration were reduced during recombinant bovine granulocyte colony stimulatory factor treatment compared with placebo or baseline levels. Ingestion of bacteria and cytotoxicity by neutrophils was increased during recombinant bovine granulocyte colony stimulatory factor therapy compared with placebo or baseline levels. Shedding of S. aureus in lacteal secretions was unaffected by recombinant bovine granulocyte colony stimulatory factor treatment. In summary, administration of recombinant bovine granulocyte colony stimulatory factor increased the number and functional activity of neutrophils and prevented some aspects of periparturient immunosuppression in dairy cows.


Expectoration in the gastrointestinal tract. A diagnostic problem in In-111 granulocyte scintigraphy.
Scintigraphic detection of infectious foci with In-111 labeled granulocytes or leukocytes is a well-established technique in nuclear medicine. The technique is commonly used to demonstrate inflammatory activity in Crohn's disease and ulcerative colitis. Its application, however, may be influenced by infectious expectoration located within the gastrointestinal tract. In performing this technique, it is important to have this differential diagnostic possibility in mind; it can be clarified by repeated imaging.


Peripapillary schisis with serous detachment in advanced glaucoma.
To describe features associated with the development and resolution of peripapillary retinoschisis with an underlying serous detachment in a patient with primary open angle glaucoma. This presentation occurred in the absence of an observed optic nerve coloboma, congenital, or acquired optic nerve head pit. A patient with advanced glaucomatous optic nerve cupping developed a temporally localized peripapillary serous detachment in the right eye which spontaneously resolved. Optical coherence tomography demonstrated an area of retinoschisis with underlying serous detachment contiguous with the temporal disc margin. Although fluorescein angiography was not performed and the presence of a peripapillary subretinal neovascular membrane could not be ruled out, an atypical coloboma, optic nerve head pit, or peripapillary subretinal neovascular membrane was not observed during biomicroscopy or scanning laser ophthalmoscopy. The retinoschisis and detachment resolved without intervention. Peripapillary retinoschisis with an underlying serous detachment may develop in subjects with advanced glaucoma. Although the occurrence of the findings in this case may be unrelated to glaucomatous optic neuropathy, the likelihood that a pathogenic mechanism linked to advanced glaucoma may be responsible for the development of peripapillary schisis and serous detachment should alternatively be taken into consideration. This case documents its spontaneous resolution without intervention.


Impairment of Everyday Spatial Navigation Abilities in Mild Cognitive Impairment Is Weakly Associated with Reduced Grey Matter Volume in the Medial Part of the Entorhinal Cortex.
Research in rodents identified specific neuron populations encoding information for spatial navigation with particularly high density in the medial part of the entorhinal cortex (ERC), which may be homologous with Brodmann area 34 (BA34) in the human brain. The aim of this study was to test whether impaired spatial navigation frequently occurring in mild cognitive impairment (MCI) is specifically associated with neurodegeneration in BA34. The study included baseline data of MCI patients enrolled in the Alzheimer's Disease Neuroimaging Initiative with high-resolution structural MRI, brain FDG PET, and complete visuospatial ability scores of the Everyday Cognition test (VS-ECog) within 30 days of PET. A standard mask of BA34 predefined in MNI space was mapped to individual native space to determine grey matter volume and metabolic activity in BA34 on MRI and on (partial volume corrected) FDG PET, respectively. The association of the VS-ECog sum score with grey matter volume and metabolic activity in BA34, APOE4 carrier status, age, education, and global cognition (ADAS-cog-13 score) was tested by linear regression. BA28, which constitutes the lateral part of the ERC, was used as control region. The eligibility criteria led to inclusion of 379 MCI subjects. The VS-ECog sum score was negatively correlated with grey matter volume in BA34 (β= -0.229, p = 0.022) and age (β= -0.124, p = 0.036), and was positively correlated with ADAS-cog-13 (β= 0.175, p = 0.003). None of the other predictor variables contributed significantly. Impairment of spatial navigation in MCI is weakly associated with BA34 atrophy.


Neuron Subpopulations with Different Elongation Rates and DCC Dynamics Exhibit Distinct Responses to Isolated Netrin-1 Treatment.
Correct wiring of the nervous system requires guidance cues, diffusible or substrate-bound proteins that steer elongating axons to their target tissues. Netrin-1, the best characterized member of the Netrins family of guidance molecules, is known to induce axon turning and modulate axon elongation rate; however, the factors regulating the axonal response to Netrin-1 are not fully understood. Using microfluidics, we treated fluidically isolated axons of mouse primary cortical neurons with Netrin-1 and characterized axon elongation rates, as well as the membrane localization of deleted in colorectal cancer (DCC), a well-established receptor of Netrin-1. The capacity to stimulate and observe a large number of individual axons allowed us to conduct distribution analyses, through which we identified two distinct neuron subpopulations based on different elongation behavior and different DCC membrane dynamics. Netrin-1 reduced the elongation rates in both subpopulations, where the effect was more pronounced in the slow growing subpopulation. Both the source of Ca(2+) influx and the basal cytosolic Ca(2+) levels regulated the effect of Netrin-1, for example, Ca(2+) efflux from the endoplasmic reticulum due to the activation of Ryanodine channels blocked Netrin-1-induced axon slowdown. Netrin-1 treatment resulted in a rapid membrane insertion of DCC, followed by a gradual internalization. DCC membrane dynamics were different in the central regions of the growth cones compared to filopodia and axon shafts, highlighting the temporal and spatial heterogeneity in the signaling events downstream of Netrin-1. Cumulatively, these results demonstrate the power of microfluidic compartmentalization and distribution analysis in describing the complex axonal Netrin-1 response.


Intralymphocyte free magnesium in a group of subjects with essential hypertension.
Despite the importance of magnesium in essential hypertension, few data are available on the ionized intracellular concentration of this ion. We therefore studied intralymphocyte free intracellular magnesium (Mgi) in 32 untreated essential hypertensive subjects and 27 normotensive control subjects by means of a fluorimetric technique based on the use of the new magnesium-sensitive dye furaptra. We also measured intralymphocyte ionized calcium (Cai) with fura 2. No statistically significant differences were found in Mgi in hypertensive compared with normotensive subjects (essential hypertensive, 0.291 +/- 0.053 mmol/L; normotensive, 0.293 +/- 0.043 [mean +/- SD]). A statistically significant inverse correlation was established between Mgi and plasma triglycerides in essential hypertensive subjects (r = -.521, P = .002). The hypertensive group was arbitrarily divided into two subgroups according to plasma triglyceride levels (> 2 [n = 10] or < 2 mmol/L [n = 22]), and Mgi proved to be significantly lower in the subgroup with high plasma triglyceride levels compared with either the subgroup with normal triglycerides (P = .009; 95% confidence interval, 0.013-0.088) or the normotensive control group as a whole (P = .03; 95% confidence interval, 0.003-0.069) (high-triglyceride hypertensive subgroup, Mgi = 0.256 +/- 0.045 mmol/L; normal-triglyceride hypertensive subgroup, Mgi = 0.307 +/- 0.049). No statistically significant differences were found in Cai in hypertensive compared with normotensive subjects (hypertensive, 53 +/- 12 nmol/L; normotensive, 54 +/- 14). We did not find statistically significant correlations between Cai and plasma triglycerides, nor did we find any differences in Cai between the subgroup of hypertensive subjects with high plasma triglyceride levels and either the subgroup of hypertensive subjects with normal triglycerides or the normotensive control group as a whole. The discrepancies between our results in lymphocytes and data relating to either erythrocytes or platelets emphasize the need for caution before the results are extrapolated from one tissue to the other. The decreased Mgi levels in the subgroup of high-triglyceride hypertensive subjects may suggest a role for magnesium in plurimetabolic syndrome.


Glass transition and phase state of organic compounds: dependency on molecular properties and implications for secondary organic aerosols in the atmosphere.
Recently, it has been proposed that organic aerosol particles in the atmosphere can exist in an amorphous semi-solid or solid (i.e. glassy) state. In this perspective, we analyse and discuss the formation and properties of amorphous semi-solids and glasses from organic liquids. Based on a systematic survey of a wide range of organic compounds, we present estimates for the glass forming properties of atmospheric secondary organic aerosol (SOA). In particular we investigate the dependence of the glass transition temperature T(g) upon various molecular properties such as the compounds' melting temperature, their molar mass, and their atomic oxygen-to-carbon ratios (O:C ratios). Also the effects of mixing different compounds and the effects of hygroscopic water uptake depending on ambient relative humidity are investigated. In addition to the effects of temperature, we suggest that molar mass and water content are much more important than the O:C ratio for characterizing whether an organic aerosol particle is in a liquid, semi-solid, or glassy state. Moreover, we show how the viscosity in liquid, semi-solid and glassy states affect the diffusivity of those molecules constituting the organic matrix as well as that of guest molecules such as water or oxidants, and we discuss the implications for atmospheric multi-phase processes. Finally, we assess the current state of knowledge and the level of scientific understanding, and we propose avenues for future studies to resolve existing uncertainties.


Cbl-b negatively regulates TLR/MyD88-mediated anti-Toxoplasma gondii immunity.
This is the first report that a human E3 ubiquitin ligase, Casitas B-lineage lymphoma proto-oncogene B (Cbl-b), functions as a host dependency factor for the intracellular protozoan Toxoplasma gondii and the mechanism for how T. gondii infection inhibits the TLR/MyD88 innate immunity pathway through MyD88 degradation mediated by Cbl-b. This finding is an impactful contribution for understanding the host cell immunity against T. gondii infection.


[Leading drugs in 1995: success, failures and uncertainties].
Presentation of drugs most worthy of interest in autumn 1995. Among these, the ACE inhibitors, the HMGCOA inhibitors, the Proton Pump inhibitors, the serotoninergics used against depression and migraine, the endobronchial corticoids and finally the ASA. Review of their successes, failures and uncertainties.


Neuroglobin overexpression inhibits oxygen-glucose deprivation-induced mitochondrial permeability transition pore opening in primary cultured mouse cortical neurons.
Neuroglobin (Ngb) is an endogenous neuroprotective molecule against hypoxic/ischemic brain injury, but the underlying mechanisms remain largely undefined. Our recent study revealed that Ngb can bind to voltage-dependent anion channel (VDAC), a regulator of mitochondria permeability transition (MPT). In this study we examined the role of Ngb in MPT pore (mPTP) opening following oxygen-glucose deprivation (OGD) in primary cultured mouse cortical neurons. Co-immunoprecipitation (Co-IP) and immunocytochemistry showed that the binding between Ngb and VDAC was increased after OGD compared to normoxia, indicating the OGD-enhanced Ngb-VDAC interaction. Ngb overexpression protected primary mouse cortical neurons from OGD-induced neuronal death, to an extent comparable to mPTP opening inhibitor, cyclosporine A (CsA) pretreatment. We further measured the role of Ngb in OGD-induced mPTP opening using Ngb overexpression and knockdown approaches in primary cultured neurons, and recombinant Ngb exposure to isolated mitochondria. Same as CsA pretreatment, Ngb overexpression significantly reduced OGD-induced mPTP opening markers including mitochondria swelling, mitochondrial NAD(+) release, and cytochrome c (Cyt c) release in primary cultured neurons. Recombinant Ngb incubation significantly reduced OGD-induced NAD(+) release and Cyt c release from isolated mitochondria. In contrast, Ngb knockdown significantly increased OGD-induced neuron death, and increased OGD-induced mitochondrial NAD(+) release and Cyt c release as well, and these outcomes could be rescued by CsA pretreatment. In summary, our results demonstrated that Ngb overexpression can inhibit OGD-induced mPTP opening in primary cultured mouse cortical neurons, which may be one of the molecular mechanisms of Ngb's neuroprotection.


Benchmarking heterogeneous electrocatalysts for the oxygen evolution reaction.
Objective evaluation of the activity of electrocatalysts for water oxidation is of fundamental importance for the development of promising energy conversion technologies including integrated solar water-splitting devices, water electrolyzers, and Li-air batteries. However, current methods employed to evaluate oxygen-evolving catalysts are not standardized, making it difficult to compare the activity and stability of these materials. We report a protocol for evaluating the activity, stability, and Faradaic efficiency of electrodeposited oxygen-evolving electrocatalysts. In particular, we focus on methods for determining electrochemically active surface area and measuring electrocatalytic activity and stability under conditions relevant to an integrated solar water-splitting device. Our primary figure of merit is the overpotential required to achieve a current density of 10 mA cm(-2) per geometric area, approximately the current density expected for a 10% efficient solar-to-fuels conversion device. Utilizing the aforementioned surface area measurements, one can determine electrocatalyst turnover frequencies. The reported protocol was used to examine the oxygen-evolution activity of the following systems in acidic and alkaline solutions: CoO(x), CoPi, CoFeO(x), NiO(x), NiCeO(x), NiCoO(x), NiCuO(x), NiFeO(x), and NiLaO(x). The oxygen-evolving activity of an electrodeposited IrO(x) catalyst was also investigated for comparison. Two general observations are made from comparing the catalytic performance of the OER catalysts investigated: (1) in alkaline solution, every non-noble metal system achieved 10 mA cm(-2) current densities at similar operating overpotentials between 0.35 and 0.43 V, and (2) every system but IrO(x) was unstable under oxidative conditions in acidic solutions.


Lipid-mediated gene transfer of viral IL-10 prolongs vascularized cardiac allograft survival by inhibiting donor-specific cellular and humoral immune responses.
The gene encoding the immunosuppressive cytokine viral interleukin-10 (vIL-10) was introduced into BALB/c (H-2d) vascularized cardiac allografts by perfusing the graft vasculature with DNA-liposome complexes, utilizing the experimental cationic lipid gamma AP DLRIE/DOPE and a plasmid encoding vIL-10 under the control of the HCMVie promoter. The DNA to lipid ratio and DNA dose were critical factors in obtaining optimal biologic effects. Gene transfer of vIL-10 with a 3:1 DNA to lipid weight ratio using 375 micrograms DNA significantly prolonged allograft survival in MHC-mismatched C57BL/6 (H-2b) recipients (16.00 days) compared with both unmodified allografts (8.14 days) and vIL-10 antisense controls (8.28 days). Enhanced graft survival was specific to vIL-10 expression since treatment with antisense plasmid or anti-vIL-10 monoclonal antibody (mAb) abrogated the effect. Prolonged survival was associated with a novel histology characterized by a moderate mononuclear infiltrate, edema, and diffuse fibrillar/collagen deposition in the interstitium. Despite these morphologic changes, myocytes remained viable and vessels were patent. Limiting dilution analysis revealed transient infiltration of IL-2 secreting, donor-reactive, helper T lymphocytes (HTL) and cytotoxic T lymphocytes (CTL) in vIL-10 expressing grafts on day 7, that decreased significantly by day 14. Similarly, vIL-10 gene transfer inhibited the accumulation of donor-specific HTL and CTL in the spleen, compared with antisense controls. Prolonged survival was also associated with a marked decrease in IgM and IgG alloantibody production, with little to no IgG isotype switching. These results show that viral IL-10 gene transfer inhibits graft rejection in a clinically relevant model by inhibiting donor-specific cellular and humoral immune responses.


Dopamine D2S and D2L receptors may differentially contribute to the actions of antipsychotic and psychotic agents in mice.
Regulation of dopamine D2 receptor (D2) function plays an important role in alleviating either the motor deficits of Parkinson's disease or psychotic symptoms of schizophrenia. D2 also plays a critical role in sensorimotor gating which can be measured by monitoring the prepulse inhibition of the startle response. Alternative splicing of the D2 gene generates two isoforms, D2S and D2L. Here we investigated the role of D2S and D2L in the mechanisms of action of dopaminergic drugs, using mice lacking D2L (D2L(-/-)) but expressing D2S as a model system. We found that the typical antipsychotic raclopride was much less potent in inhibiting locomotor activity and eliciting catalepsy (or parkinsonism) in D2L(-/-) mice, whereas the atypical antipsychotic clozapine was equally effective in D2L(-/-) and wild-type mice. These suggest that the deletion of D2L diminishes drug-induced parkinsonism. Furthermore, two dopamine agonists, amphetamine and apomorphine, reduced prepulse inhibition to a similar degree in D2L(-/-) and wild-type mice. These results together suggest that D2S alone can mediate the action of clozapine and the dopamine agonist-induced disruption of prepulse inhibition. The differential binding affinities of these agents for D2S vs D2L were not sufficient to explain the divergent effects of typical vs atypical antipsychotics in D2L(-/-) mice. These findings suggest that D2S and D2L may differentially contribute to the therapeutic actions and side effects of antipsychotic agents, and may have implications for developing better antipsychotic agents.


Spatially-resolved mapping of history-dependent coupled electrochemical and electronical behaviors of electroresistive NiO.
Bias-induced oxygen ion dynamics underpins a broad spectrum of electroresistive and memristive phenomena in oxide materials. Although widely studied by device-level and local voltage-current spectroscopies, the relationship between electroresistive phenomena, local electrochemical behaviors, and microstructures remains elusive. Here, the interplay between history-dependent electronic transport and electrochemical phenomena in a NiO single crystalline thin film with a number of well-defined defect types is explored on the nanometer scale using an atomic force microscopy-based technique. A variety of electrochemically-active regions were observed and spatially resolved relationship between the electronic and electrochemical phenomena was revealed. The regions with pronounced electroresistive activity were further correlated with defects identified by scanning transmission electron microscopy. Using fully coupled mechanical-electrochemical modeling, we illustrate that the spatial distribution of strain plays an important role in electrochemical and electroresistive phenomena. These studies illustrate an approach for simultaneous mapping of the electronic and ionic transport on a single defective structure level such as dislocations or interfaces, and pave the way for creating libraries of defect-specific electrochemical responses.


Taxonomy of freshwater sponges of Maharashtra, India, with illustrated descriptions and notes on ecology and habitats (Porifera: Spongillida: Spongillidae).
We present additional taxonomic descriptions, with Scanning Electron Microscopy (SEM) illustrations, field observations documented by colour photographs, and notes on habitats and ecology of Corvospongilla ultima (Annandale), Eunapius crassissimus (Annandale), Stratospongilla bombayensis (Carter), S. gravelyi (Annandale) and S. indica (Annandale) from recent sponge collections made in western Maharashtra, India. Stratospongilla gravelyi is rediscovered after a century, and along with it, C. ultima and S. indica are illustrated with SEM images for the first time, unequivocally differentiating these two species. Additional taxonomic, ecological data and illustrations of Corvospongilla lapidosa (Annandale), Dosilia plumosa (Carter), Ephydatia meyeni (Carter), Eunapius carteri (Bowerbank) and Radiospongilla cerebellata (Bowerbank) are also provided to supplement the previously published SEM illustrations. All ten spongillid species treated here were originally described from India and three of them are known to be endemic to the Indian region. Present study is the first re-examination of these Indian spongillid species using SEM, providing greater resolution of their important taxonomic characters and careful documentation of their habitats.


An evaluation of the processing conditions, structure, and properties (biaxial flexural strength and antibacterial efficacy) of sintered strontium-zinc-silicate glass ceramics.
The use of artificial bone grafts has increased in order to satisfy a growing demand for bone replacement materials. Initial mechanical stability of synthetic bone grafts is very advantageous for certain clinical applications. Coupled with the advantage of mechanical strength, a material with inherent antibacterial properties would be very beneficial. A series of strontium-doped zinc silicate (Ca-Sr-Na-Zn-Si) glass ceramics have been characterized in terms of their crystalline structure, biaxial flexural strength and antibacterial efficacy based on the identification of optimum sintering conditions. All three glass ceramics, namely, BT110, BT111, and BT112 were found to be fully crystalline, with BT111 and BT112 comprising of biocompatible crystalline phases. The biaxial flexural strengths of the three glass ceramics ranged from 70 to 149 MPa and were shown to be superior to those of clinically established ceramics in dry conditions and following incubation in simulated physiological conditions. The bacteriostatic effect for each glass ceramic was also established, where BT112 showed an inhibitory effect against three of the most common bacteria found at implantation sites, namely, Enterococcus faecalis, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa. The results of the evaluation suggest that the materials studied offer advantages over current clinical materials and indicate the potential suitability of the glass ceramics as therapeutic bone grafts.


Inhibition of apolipoprotein E-related neurotoxicity by glycosaminoglycans and their oligosaccharides.
Apolipoprotein E (apoE) has been genetically linked to late-onset Alzheimer's disease (AD). The role of this lipid-transport protein in AD remains to be established. One hypothesis is that apoE, particularly the apoE4 isoform, may have neurotoxic effects as demonstrated using apoE-related synthetic peptides and the N-terminal fragment of apoE. ApoE is a heparan-sulfate binding protein, and apoE peptide neurotoxicity can be blocked by heparin and prevented by degrading heparan sulfate or inhibiting its biosynthesis. The possibility that heparin inhibition of toxicity is mediated by a specific oligosaccharide sequence was investigated using a bioassay to determine the inhibition of apoE peptide toxicity by glycosaminoglycans and purified glycosaminoglycan oligosaccharides. Studies on modified heparins showed that the presence of N-sulfo groups and either 2- or 6-O sulfo groups were required for inhibition of toxicity. Heparin oligosaccharides with eight or more saccharide residues with seven O-sulfo groups and four N-sulfo groups exhibited potent inhibition. Larger oligosaccharides, and heparin and heparan sulfate polymers, afforded comparable, or somewhat better, protective effects but also caused clumping and detachment of cells when administrated alone.


Brain microstructure mediates sex-specific patterns of cognitive aging.
Normal brain aging is characterized by declining neuronal integrity, yet it remains unclear how microstructural injury influences cognitive aging and whether such mechanisms differ between sexes. Using restriction spectrum imaging (RSI), we examined sex differences in associations between brain microstructure and cognitive function in 147 community-dwelling older men and women (56-99 years). Gray and white matter microstructure correlated with global cognition, executive function, visuospatial memory, episodic memory, and logical memory, with the strongest associations for restricted, hindered and free isotropic diffusion. Associations were stronger for women than for men, a difference likely due to greater age-related variability in cognitive scores and microstructure in women. Isotropic diffusion mediated effects of age on cognition for both sexes, though distinct mediation patterns were present for women and men. For women, hippocampal and corpus callosum microstructure mediated age effects on verbal and visuospatial memory, respectively, whereas for men fiber microstructure (mainly fornix and corpus callosum) mediated age effects on executive function and visuospatial memory. These findings implicate sex-specific pathways by which changing brain cytoarchitecture contributes to cognitive aging, and suggest that RSI may be useful for evaluating risk for cognitive decline or monitoring efficacy of interventions to preserve brain health in later life.


A multi-state, multi-site, multi-sector healthcare improvement model: implementing evidence for practice.
Healthcare is complex and we know that evidence takes nearly 20 years to find its way into clinical practice. The slow process of translating research points to the need for effective translational research models to ensure patient care quality and safety are not compromised by such an epistemic failure. Our model to achieve reasonably rapid and enduring improvements to clinical care draws on that developed and promulgated by the Institute for Healthcare Improvement in the United States of America model as well as that developed by the Johns Hopkins Quality and Safety Group known as the Translating Research into Practice implementation model. The core principle of our hybrid model was to engage those most likely to be affected by the changes being introduced through a series of face-to-face and web-enabled meetings that act both as drivers of information but also as a means of engaging all stakeholders across the healthcare system involved in the change towards their pre-established goals. The model was piloted on the focused topic of the management of inadvertent perioperative hypothermia across nine hospitals within Australia (four sites in Victoria, three sites in New South Wales and two sites in Queensland). Improvement in management of hypothermia in these patients was achieved and sustained over time. Our model aims to engage the hearts and minds of healthcare clinicians, and others in order to empower them to make the necessary improvements to enhance patient care quality and safety.


SCG10 expression on activation of hepatic stellate cells promotes cell motility through interference with microtubules.
During liver fibrogenesis, quiescent hepatic stellate cells switch their phenotype toward a myofibroblastic-like pattern with a gain in motility. Here, we show that SCG10 (superior cervical ganglia 10) mRNA expression, a microtubule-destabilizing protein that favors cell growth and motility in neurons, both increases and correlates with the stage of fibrosis in patients with chronic hepatitis C. We also show the de novo expression of SCG10 mRNA in two rat models of liver fibrosis. We demonstrate that activated hepatic stellate cells appear to be the major cellular sources of SCG10 in the liver. Tracking of the SCG10 pathway in hepatic stellate cells shows that SCG10 initially accumulates in the perinuclear Golgi area then migrates in small vesicle-like structures along individual microtubules. Moreover, SCG10 vesicles cluster at the distal ends of microtubules in areas where tubules are spread and decompacted, suggesting their preferential association with destabilized and dynamic microtubules. Inhibition of SCG10 expression by gene-specific short interfering RNA in primary rat hepatic stellate cells is associated with a significant reduction in microtubule-dependent cellular functions, such as proliferation and migration. In conclusion, the de novo expression of SCG10 by hepatic stellate cells may play a major role in cellular mechanisms associated with HSC activation, namely cell motility and division, through interference with microtubules. SCG10 may represent a potential molecular target for anti-fibrosis therapies.


Matrix induced re-differentiation of cultured rat hepatocytes and changes of CCAAT/enhancer binding proteins.
Rat hepatocytes de-differentiate and proliferate when cultured on collagen-coated dishes in a chemically defined Hepatocyte Growth Medium in the presence of hepatocyte growth factor and epidermal growth factor. The addition of biomatrix derived from Engelbreth-Holm-Swarm (EHS) mouse sarcoma stops this process and leads to re-differentiation of the cells. We monitored DNA binding activity and protein levels of CCAAT/Enhancer Binding Proteins (C/EBPs) during these events by electrophoretic mobility shift assays and western blot analysis. We used plasma protein gene expression as a marker for the proliferation and differentiation phases. During the initial proliferation phase the DNA binding activity of C/EBPs decreased about 5-10 fold, mainly due to reduction of C/EBP alpha protein to nearly undetectable levels. Addition of EHS-gel prevented the further loss of C/EBP alpha protein and established a new steady state level. Since C/EBP beta proteins were affected to a much lesser extent, the C/EBP alpha:C/EBP beta ratio was greater in the presence of EHS-gel. Transferrin, alpha 1-antitrypsin, and albumin mRNA expression increased substantially. Thus stabilized C/EBP alpha expression, an increased C/EBP alpha:C/EBP beta ratio, and increased expression of liver specific mRNAs all correlated with the transition of proliferative to differentiated cells.


Effects of age on the thickness of myelin sheaths in monkey primary visual cortex.
The effect of age on myelin sheath thickness was determined by an electron microscopic examination of cross sections of the vertical bundles of nerve fibers that pass through primary visual cortex of the rhesus monkey. The tissue was taken from the cortices of young (4-9 years of age) and old (over 24 years of age) monkeys, and the sections were taken at the level of layer 4Cbeta. From the electron photomicrographs, the diameters of axons and the numbers of lamellae in their myelin sheaths were determined. No change was found in the diameters of axons with age, although the mean numbers of myelin lamellae in the sheaths increased from 5.6 in the young monkeys to 7.0 in the old monkeys. Much of this increase in mean thickness was due to the fact that, in the old monkeys, thick myelin sheaths with more than ten lamellae are more common than in the young monkeys. While this increase in the thickness of myelin sheaths is occurring in old monkeys, there are also age-related changes in some of the sheaths. Consequently, it seems that, with age, there is some degeneration of myelin but, at the same time, a continued production of lamellae.


Inactivated orf virus (Parapoxvirus ovis) induces antitumoral activity in transplantable tumor models.
Orf virus (ORFV, Parapoxvirus ovis) possesses strong immunomodulating activity including the induction of interferon gamma (IFN-γ) and interleukin-12 (IL-12) expression. Antiviral effects have been described which appeared to be facilitated by an ORFV-induced Type 1 helper T-cell (Th1-type) immune response. In this study, we investigated the potential antitumoral activity of inactivated ORFV in transplantable tumor models. We show that parenteral administration of inactivated ORFV mediates antitumor effects in various models including the murine syngenic B16 F10 melanoma and MDA-MB-231 human breast cancer xenograft. Inhibition of natural killer (NK) and NKT cell activity through administration of an anti-mouse NK-1.1 antibody led to a reduction of ORFV-mediated antitumoral effects. However, residual antitumoral activity was observed. This observation was confirmed in MDA-MB-231 tumor-bearing NOD/LtSz-scid/j mice which not only lack functional T and B lymphocytes but, in addition, have virtually no cells positive for the NK 1.1 cell surface marker. Thus, administration of inactivated ORFV induced inhibitory effects on the growth of transplantable tumors even under conditions of severe immunosuppression.


A new radioimmunoassay detecting early stages of colon cancer: a comparison with CEA, AFP, and Ca 19-9.
A previous study reported the results of a radioimmunoassay that analysed immune complexes (IC) with a specific labeled polyclonal antibody for the detection of the early stages of colon cancer. In order to investigate further the possible clinical use of this assay, a blind study that screened 505 patients referred for colonoscopy, compared their pathology reports with the results of four assays that measure levels of circulating tumor markers. These were CEA, AFP, Ca 19-9, and our previously described radioimmunoassay (RIA). Of the patients with no malignancies, the results that were in the normal range were as follows: CEA-473/495 (95.6 per cent), Ca 19-9-486/495 (98.2 per cent) and our RIA-488/495 (98.6 per cent). AFP levels were in the normal range for all patients in the study. The only assay to identify any Dukes' C and D patients was Ca 19-9, which detected 2/3 (67 per cent). Of the patients with Dukes' A and B colon cancer, CEA only identified 1/7 (14 per cent), AFP and Ca 19-9 0/7 (0 per cent), and our own RIA 5/7 (71 per cent). The positive results of our assay were significantly different from those of the other three assays with p values all less than 0.05. These preliminary results suggest that this RIA, because of its ability to detect the early stages of colon cancer, may be an effective complement to the currently available assays. The combination may provide a more comprehensive evaluation in monitoring colon cancer.


Agencies make a difference in home healthcare nurses' job satisfaction.
The purpose of this study was to explore the factors that contribute to variability in home healthcare nurses' job satisfaction. Nurses completed the 30-item Home Healthcare Nurses Job Satisfaction Scale specifically designed to measure job satisfaction of home healthcare nurses. Results suggest that the greatest amount of variability in satisfaction for home healthcare nurses are salary and benefits, stress and workload, and organizational factors, that is, factors over which organizations and management have the most control.


The AOA/ACGME Single Accreditation System and Its Immediate and Future Impact on Family Medicine.
The American Osteopathic Association (AOA) agreed to combine its graduate medical education programs with the Accreditation Council for Graduate Medical Education (ACGME) between July 1, 2015 and June 30, 2020 in an initiative called the Single Accreditation System (SAS). The objective of our study was to identify the impact the SAS had on the ACGME, family medicine (FM), and implications for the future of FM. We collected and compiled data from the AOA, ACGME, and the National Residency Matching Program (NRMP). Analysis reveals the effects that the addition of former 122 AOA-accredited FM residencies had on the ACGME and FM programs. Several osteopathic FM programs encountered challenges meeting ACGME accreditation standards. As of June 1, 2020, 89 of 122 accreditation applications received initial or continuing accreditation; the others had accreditation issues to resolve. The Osteopathic Recognition program emphasizing training in osteopathic principles and practices was a popular option in FM residencies. Fewer DOs serve as program directors in former AOA-accredited FM residencies. The SAS has shifted the balance in the percentages of MDs, DOs, and international medical graduates (IMGs) in FM. Trends in FM show that as more DOs enter the NRMP the percent of MDs and IMGs decreases. In the future, it is projected that DOs will outnumber MDs and IMGs in ACGME FM residencies. The 51 new medical schools started between 2010 and 2020 will generate a test for the integration of their graduates into GME. Increased competition for FM residencies is expected.


Visual receptive field properties in kitten pretectal nucleus of the optic tract and dorsal terminal nucleus of the accessory optic tract.
1. Neurons in the pretectal nucleus of the optic tract (NOT) and dorsal terminal nucleus of the accessory optic tract (DTN) were recorded in anesthetized and paralyzed kittens on postnatal days 18 to 48 (P18-P48) as well as in adult cats. 2. Spontaneous as well as stimulus driven discharge rates of NOT-DTN neurons in the youngest kittens (P18-P23) are significantly lower than in older kittens (P27-P33) or adult cats. 3. Visual latencies of NOT-DTN neurons in P18-P23 kittens are significantly longer than in P27-P33 kittens. They further decrease as the animals reach adulthood. 4. Already in the youngest animals recorded in this experimental series (P18) NOT-DTN neurons were selective for ipsiversive horizontal stimulus movement. When expressed as the difference between response strength during stimulation in the preferred and the nonpreferred direction, P18-P23 NOT-DTN neurons are less direction selective than NOT-DTN cells in older animals. However, the normalized directional tuning expressed as percent change in discharge rate per degree change in stimulus direction away from the preferred direction (where discharge rate is set 100%) is about equal in all age groups. 5. NOT-DTN neurons in P18-P23 kittens respond to a rather limited range of stimulus speeds with an optimum at approximately 10 degrees/s. In P27-P33 kittens, NOT-DTN neurons increase their responsive range to higher stimulus speeds. As the animals approach adulthood, the range of effective stimulus speeds further broadens to include very low ones. 6. In P18-P23 kittens, the majority of NOT-DTN neurons is exclusively activated by the contralateral eye; only a few neurons receive an additional input from the ipsilateral eye. In P27-P48 kittens, the influence of the ipsilateral eye has significantly increased but with the majority of NOT-DTN cells still being dominated by the contralateral eye. Finally, in adults, a further strengthening of the ipsilateral input leads to a more binocularly balanced input to NOT-DTN cells. 7. Electrical stimulation in areas 17 and 18 did not elicit orthodromic action potentials in NOT-DTN neurons before P27. Thus the cortical input to the NOT-DTN in kittens becomes functional only at 4 wk of age. 8. In conclusion, the significant changes of visual response properties of NOT-DTN neurons coincide with the time when the cortical input to the NOT-DTN becomes functional.(ABSTRACT TRUNCATED AT 400 WORDS)


ApoE induces serum paraoxonase PON1 activity and stability similar to ApoA-I.
Serum paraoxonase (PON1) is an anti-atherogenic interfacially activated lipo-lactonase that was shown to selectively bind high-density lipoprotein (HDL) carrying apolipoprotein A-I (apoA-I). ApoA-I binding occurs with nanomolar affinity and induces a dramatic increase in enzyme stability and lactonase activity. This study examined the association of PON1 with reconstituted HDL (rHDL) carrying apolipoprotein E, and its consequences on the stability and enzymatic activity of PON1, and on its anti-atherogenic potential. The results indicate that reconstituted HDL particles prepared with two most common isoforms of apoE (apoE3 and apoE4) associate with rePON1 in a manner and affinity similar to those of apoA-I. Binding to apoE-HDL stimulates the lactonase activity and stabilizes the enzyme, although the latter occurs to a >10-fold lesser extent compared to apoA-I-HDL particles. The anti-atherogenic potential of PON1, measured by inhibition of LDL oxidation and stimulation of macrophage cholesterol efflux, was also stimulated by apoE-HDL, at levels of 40-96% compared to apoA-I-HDL. Overall, reconstituted apoE-HDL exhibits properties similar to those of apoA-I-HDL, but with a lower capacity to stabilize PON1 and to induce its anti-atherogenic functions. ApoE, apoA-I, and to a lesser degree apoA-IV show distinct structural and functional similarities but little sequence homology. That these apolipoproteins, but not apoA-II, bind PON1 with high affinity and stimulate its activity suggests that PON1-HDL recognition is based primarily on surface properties of the apolipoproteins and that specific protein-protein interactions may play only a secondary role.


Transplantation for end stage liver disease related to alpha 1 antitrypsin.
Alpha 1 antitrypsin deficiency (AT) is an autosomal recessive disease associated with chronic liver disease in adults and children and emphysema in adults. The disease is one of the most common inherited disorders of the Caucasian population of North Europe and North America and is the most common genetic reason for pediatric orthotopic liver transplantation (OLTx), although it is a rare indication in adults. The natural history of the disease is unpredictable and the pathogenesis of the liver injury unclear. Thirty-five patients with histologically apparent alpha 1 AT accumulation in the liver (22 adults, 13 children) have been transplanted in this center. Clinical features were correlated with the pretransplant phenotype, serum alpha 1 antitrypsin levels and potential precipitating factors. All children were PiZZ homozygotes, most of whom had presented with neonatal hepatitis. The majority of adult patients were heterozygotes presenting with portal hypertension and liver cirrhosis. Current one-year posttransplant survival figures are 73% for adults and 87.5% for children. Replacement of the cirrhotic liver results in acquisition of the donor phenotype, a rise in serum levels of alpha 1 antitrypsin, and apparent prevention of associated disease.


Dose-dependent radiation effect on microvasculature and repair.
It has been postulated that the damage to microvasculature may be a major factor in the manifestation of late radiation damage to organized tissue. In this study, the radiation damage to microvasculature was investigated in a rabbit model during the early phases of irradiation with the use of vascular permeability as a marker. By means of a triple isotopic technique, the vascular, extravascular, and intracellular spaces could be defined. A forelimb and hindlimb of New Zealand White rabbits were irradiated with single doses of 2-30 Gy. 125I- and 131I-labeled bioscreened albumin were used to determine the changes in vascular permeability due to irradiation. The rabbits were sacrificed at various intervals post irradiation. Vascular and extravascular spaces and the respective albumin concentrations in tissue samples from irradiated limbs were compared with control values from the unirradiated contralateral limbs in each animal. The results indicated a definite increase in the vascular permeability of albumin secondary to irradiation. The increase in vascular permeability was apparent instantaneously with irradiation, even at 2 Gy. The microvascular compromise appear to be dose related. When examined at 16-24 hours post irradiation, the excess extravasation of albumin was significant at and beyond 8 Gy. At 10-30 days post irradiation, injury was not apparent up to 15 Gy. Thus there appeared to be an instantaneous injury at the capillary level due to irradiation, which appeared to be dose related. A repair process became evident as early as 16-24 hours and appeared to be dose related as well as related to elapsed time post irradiation.


A comparison of magnetic resonance imaging and neurophysiological studies in the assessment of cervical radiculopathy.
Neurophysiological studies (NPS) are often used by both neurosurgeons and neurologists to supplement neuroimaging findings in the diagnosis of cervical radiculopathy and in operative decision-making. The aim of this study was to assess whether nerve conduction and electromyographic studies added significant information to that obtained from high resolution MRI to warrant routine use. Over the 10-year period (1991-2001), we identified 48 patients who underwent both preoperative NPS and MRI for cervical radiculopathy. Sensitivity of MRI and NPS for diagnosing cervical radiculopathy was 93 and 42%, respectively. Whilst the positive predictive values for MRI and NPS were similar (91% versus 86%), the former had a higher negative predictive value (25% versus 7%). In only one case was the decision to operate based on NPS despite a negative MRI. We therefore suggest that in patients with clinical and MRI evidence of cervical radiculopathy, NPS has limited additional diagnostic value.


The Opioid Debate-PRO: Opioids Have an Important Role in Pain Management in Children.
The increase in opioid-related deaths in the United States (and other countries) has prompted a national debate in medicine about the appropriateness of opioids for the treatment of acute and chronic pain, and specifically in children, if medical opioid use causes or increases the risk of opioid use disorder (OUD) later in life. Some in the medical community and in government advocate withholding opioids from children after an arbitrary number of days of treatment, regardless of diagnosis. Here, I argue that opioid experimentation and misuse is no more common in children and adolescents today than 2 or 3 decades ago, that there is no compelling evidence that appropriate medical use of opioids leads to OUD, and that the epidemic of inadequately treated pain in children remains the more compelling issue.


Psychological torture: definitions, clinical sequelae and treatment principles.
Psychological torture, in its broadest sense, is the intentional infliction of suffering without resorting to direct physical violence, in what is known as 'no-touch' torture. While several other definitions of psychological torture have been suggested, there is no one precise definition. Given the rapidly evolving current global political climate and the intensification of conflict, war and asylum seeking, the need for better recognition of psychological torture among clinicians, followed by the provision of appropriate treatment support for victims, has become increasingly pertinent. This article raises awareness of the concept of psychological torture among clinicians, through an overview of its debated definitions, the modalities which constitute this form of torture, and its clinical sequelae and treatment approach.


Brownie, a gene involved in building complex respiratory devices in insect eggshells.
Insect eggshells must combine protection for the yolk and embryo with provisions for respiration and for the entry of sperm, which are ensured by aeropyles and micropyles, respectively. Insects which oviposit the eggs in an egg-case have a double problem of respiration as gas exchange then involves two barriers. An example of this situation is found in the cockroach Blattella germanica, where the aeropyle and the micropyle are combined in a complex structure called the sponge-like body. The sponge-like body has been well described morphologically, but nothing is known about how it is built up. In a library designed to find genes expressed during late chorion formation in B. germanica, we isolated the novel sequence Bg30009 (now called Brownie), which was outstanding due to its high copy number. In the present work, we show that Brownie is expressed in the follicle cells localized in the anterior pole of the oocyte in late choriogenesis. RNA interference (RNAi) of Brownie impaired correct formation of the sponge-like body and, as a result, the egg-case was also ill-formed and the eggs were not viable. Results indicate that the novel gene Brownie plays a pivotal role in building up the sponge-like body. Brownie is the first reported gene involved in the construction of complex eggshell respiratory structures.


Models of fungicide resistance dynamics.
We describe two classes of models used for fungicide and antibiotic resistance dynamics. One class assumes that the density of the pathogen (or severity of the disease caused by the pathogen) has no feedback effects on the rate at which new infections arise. The second class does not make this assumption. A quantitative relationship between these two classes is derived. We then discuss the two sets of assumptions made in the literature about initial conditions: either both the fungicide-sensitive strain and the -resistant strain are initially at low density, or the sensitive strain is resident at nonlow density and the resistant strain is initially at low density. We show that models of fungicide resistance dynamics with and without density-dependent feedback give contrasting predictions on the effects of pathogen life-cycle parameters and the effects of the fungicide (dose, frequency, use of mixtures, spatial usage restrictions) on the evolution, invasion, and spread of fungicide resistance. We further show that the evaluation of a resistance management strategy requires a very precise definition of what constitutes a good strategy.


Profile of short-chain fatty acids and rectal proliferation in rats fed sucrose or cornstarch diets.
Rats were fed high fat (231 g/kg diet), low calcium (1.3 g/kg diet), low cellulose (20 g/kg diet) diets in which carbohydrates were represented by sucrose or starch (460 g/kg diet). A subgroup of animals was treated with 1,2-dimethylhydrazine (DMH) twice, 4 and 8 d before the beginning of the dietary treatments. Animals fed the starch diet, compared with those fed the sucrose diet, had higher concentrations of cecal and fecal short-chain fatty acids and a significantly lower acetic acid:butyric acid ratio in the cecal contents at d 105. Ratios were 14.7 +/- 1.7 and 6.8 +/- 0.4 for rats fed the sucrose and starch diets, respectively (P less than 0.01). Cecal pH was significantly lower in animals fed the starch diet for 105 d. At d 105, rectal proliferation was lower in rats fed the starch diet (labeled cells/crypt were 7.89 +/- 0.56 and 3.57 +/- 0.40 for rats fed the sucrose and starch diets, respectively, P less than 0.01); at d 30 the effect of starch on proliferation was evident in controls but not in DMH-treated rats. Rectal proliferation data were negatively correlated with the concentration and percentage of butyric acid and positively correlated with the percentage of acetic acid, the acetic acid:butyric acid ratio and cecal pH. These results suggest that low rectal proliferation in animals fed a high fat, high starch diet might be associated with a lower relative concentration of butyric acid in the cecal contents.


Fast Volumetric Feedback under Microscope by Temporally Coded Exposure Camera.
We developed a temporally coded exposure (TeCE) camera that can cope with high-speed focus variations of a tunable acoustic gradient index (TAG) lens. The TeCE camera can execute a very short exposure multiple times at an arbitrary timing during one shot. Furthermore, by accumulating the photoelectrons generated by each exposure, it is possible to maintain the brightness even with a short exposure time. By synchronously driving the TeCE camera and the TAG lens, different focal planes of an observation target can be acquired at high speed. As a result, high-speed three-dimensional measurement becomes possible, and this can be used for feedback of three-dimensional information. In the work described in this paper, we conducted a focus tracking experiment to evaluate the feedback performance of the TeCE camera. From the experimental results, we confirmed the feedback capability of the TeCE camera.


Sulfated galactocerebrosides as potential antiinflammatory agents.
Native sulfatides, as well as many sulfated glycolipids, have been shown to avidly bind to the selectin receptors. In vivo, native sulfatides significantly block activity in selectin-dependent inflammatory responses. The fact that nonsulfated galactocerebrosides did not inhibit selectin-mediated adhesion identified a critical role for the anionic sulfate residue. We therefore initiated a program to evaluate the activity of position isomers. This study showed a binding selectivity for the positions 2 and 3 of the sulfate group on the carbohydrate ring as well as enhanced activity for the disulfated analogs. Furthermore, it was discovered that the attachment of lipophilic substituents on the carbohydrate ring was tolerated, consistent with the presence of a lipophilic pocket in the binding activity. This resulted in compounds with a 6-fold increased potency.


Different roles of the RAAS affect bone metabolism in patients with primary aldosteronism, Gitelman syndrome and Bartter syndrome.
Components of the RAAS may influence bone metabolism. Different roles of the RAAS are found in patients with primary aldosteronism (PA), Gitelman syndrome (GS) and Bartter syndrome (BS). We collected inpatient medical records including 20 patients with Gitelman syndrome (GS group), 17 patients with Bartter syndrome (BS group) and 20 age-matched patients with primary aldosteronism (PA group). We found the following results. (1) PA patients had significantly higher serum magnesium, potassium, plasma aldosterone, serum parathyroid hormone, urinary calcium and BMI (p<0.05) while significantly lower serum calcium and phosphorus (P < 0.05) than GS and BS patients. (2) Total hip and femoral neck bone mineral density (BMD) in PA patients were significantly lower than those in GS and BS patients (P<0.05). (3) GS patients had lower serum magnesium and urinary calcium than BS patients (P < 0.05). (4) Compared with BS patients, the vertebral BMD in GS patients were significantly higher (P < 0.05). So we believe higher aldosterone and PTH levels may be the reason that PA patients have lower hip BMD. Lower urinary calcium and inactivation of the NCC gene (Na-Cl cotransporter) in GS patients may have protective effects on vertebral bone mineral density. With persistence disordered RAAS, PA patients have lower BMD, especially hip BMD as compared with GS and BS patients. We presumed the lower renin and higher aldosterone level may be the reason. With the same level of renin and aldosterone, BS patients have lower vertebrate BMD than GS patients. Decreased urinary calcium excretion may be the reason.


Role of Magnesium in the Binding of Substrate and Effectors to Phosphoenolpyruvate Carboxylase from a CAM Plant.
The binding of phosphoenolpyruvate, malate, and glucose 6-phosphate to phosphoenolpyruvate carboxylase purified from Crassula argentea Thunb. was measured using both the intrinsic tryptophan fluorescence of the enzyme and the extrinsic fluorescence of the complex of 8-anilino-1-napthalenesulfonate with the enzyme. It was found that the substrate phosphoenolpyruvate can bind in the absence of magnesium but is bound in greater quantities and more tightly when magnesium is present. Malate reduces the binding of phosphoenolpyruvate, while glucose 6-phosphate increases the binding of the substrate. Glucose 6-phosphate requires magnesium to bind to the enzyme, while malate does not. The general trends from the binding experiments using fluorescence methods were confirmed by activity determinations using assays performed in the absence of magnesium.


A concise review: iron absorption--the mucin-mobilferrin-integrin pathway. A competitive pathway for metal absorption.
Newly identified iron binding proteins isolated from rat duodenal homogenates permit better understanding of iron absorption. Mucins bind iron at acid pH to keep iron soluble and available for absorption at the more alkaline pH of the duodenum; this explains iron deficiency following prolonged achlorhydria. Integrin (90/150 kD) was identified on the absorptive surface of enterocytes in association with radioiron and is believed to facilitate transit of iron through the microvillous membrane. Mobilferrin, a 56 kD iron binding protein, was isolated from enterocyte cytosol. It coprecipitates with integrin and appears in close association with integrins in the apical cytoplasm. We postulate it accepts dietary iron from integrin and acts as the shuttle protein for iron in the cytoplasm. Since iron in enterocytes remains in equilibrium with body stores, we postulate mucosal iron uptake is regulated by the number of iron binding sites either occupied or unoccupied by iron on mobilferrin. Iron repletion of enterocytes from body stores is accomplished via transferrin receptors on the posterolateral membranes of enterocytes. Increased transfer of iron from blood into absorptive enterocytes occurs in iron replete animals to inhibit mucosal uptake of dietary iron. Little transfer of iron from plasma to enterocytes occurs in iron deficiency. Enhanced mucosal transfer of iron into the body occurs with increased body need for iron. The exact mechanism for mucosal transfer of iron into the plasma has not been defined but may also be mediated by an integrin.


Patterns of phenylpropanoids in non-inoculated and potato virus Y-inoculated leaves of transgenic tobacco plants expressing yeast-derived invertase.
The patterns of secondary metabolites in leaves of yeast invertase-transgenic tobacco plants (Nicotiana tabacum L. cv. Samsun NN) were analyzed. Plants expressing cytosolic yeast-derived invertase (cytInv) or apoplastic (cell wall associated) yeast invertase (cwInv) showed a characteristic phytochemical phenotype compared to untransformed controls (wild-type plants). The level of phenylpropanoids decreased in the cytInv plants but increased in the cwInv plants, which showed an induced de novo synthesis of a caffeic acid amide, i.e. N-caffeoylputrescine. In addition, the level of the coumarin glucoside scopolin was markedly enhanced. Increased accumulation of scopolin in the cwInv plants is possibly correlated with the induction of defense reactions and the appearance of necrotic lesions similar to the hypersensitive response caused by avirulent pathogens. This is consistent with results from potato virus Y-infected plants. Whereas there was no additional increase in the coumarins in leaves following infection in cwInv plants, wild-type plants showed a slight increase and cytInc a marked increase.


Gastroesophageal reflux in children: pathogenesis, prevalence, diagnosis, and role of proton pump inhibitors in treatment.
A substantial percentage of infants, children and adolescents experience gastroesophageal reflux disease (GERD) and its accompanying symptoms, as well as disease complications. The diagnosis of GERD in children is made based upon the child's history, and data derived primarily from pH monitoring tests and endoscopy. In those children with confirmed reflux disease, the options for management parallel those recommended in adult patients, with the first step consisting of lifestyle changes. Surgical procedures may also be performed; however, these are rarely recommended prior to an adequate course of pharmacologic therapy, and appropriate case selection is important. Among the current pharmacotherapeutic options available in the US, the prokinetic agents and the acid-inhibitory agents (histamine-2 receptor antagonists, proton pump inhibitors) are the most widely used. The clinical utility of the prokinetic agents has been limited by the recent withdrawal of cisapride from the US marketplace and the potential for irreversible central nervous system complications with metoclopramide. Numerous clinical studies performed in adults, and several studies involving children, have demonstrated that the proton pump inhibitors are more effective than the histamine-2 receptor antagonists in the relief of GERD symptoms and healing of erosive esophagitis. In children, omeprazole and lansoprazole may be administered as the intact oral capsule, or in those who are unable or unwilling to swallow, the granule contents of the capsule may be mixed with soft foods (e.g. apple sauce) or fruit drinks/liquid dietary supplements prior to oral administration with no detrimental effects on pharmacokinetics, bioavailability, or pharmacodynamics. Studies performed with omeprazole and lansoprazole in children have shown pharmacokinetic parameters that closely resemble those observed in adults. In over a decade of use in adults, the proton pump inhibitor class of agents has been found to have a good safety profile. Studies involving children have also shown these agents to be well tolerated. In numerous drug-drug interaction studies performed with these two proton pump inhibitors, relatively few clinically significant interactions have been observed.


Low-Barrier and Canonical Hydrogen Bonds Modulate Activity and Specificity of a Catalytic Triad.
The position, bonding and dynamics of hydrogen atoms in the catalytic centers of proteins are essential for catalysis. The role of short hydrogen bonds in catalysis has remained highly debated and led to establishment of several distinctive geometrical arrangements of hydrogen atoms vis-à-vis the heavier donor and acceptor counterparts, that is, low-barrier, single-well or short canonical hydrogen bonds. Here we demonstrate how the position of a hydrogen atom in the catalytic triad of an aminoglycoside inactivating enzyme leads to a thirty-fold increase in catalytic turnover. A low-barrier hydrogen bond is present in the enzyme active site for the substrates that are turned over the best, whereas a canonical hydrogen bond is found with the least preferred substrate. This is the first comparison of these hydrogen bonds involving an identical catalytic network, while directly demonstrating how active site electrostatics adapt to the electronic nature of substrates to tune catalysis.


Strategies for continual application of marker-assisted selection in an open nucleus population.
The objectives of this study were to develop and simulate the implementation of several strategies for repeated application of quantitative trait loci (QTL) detection and marker-assisted selection (MAS) and to compare the short-term and continual genetic responses. A finite locus model was simulated with 20 QTL randomly distributed across 30 chromosome. Three hundred markers were evenly spaced across the genome. Allelic effects were sampled from a double exponential distribution. A daughter design was used every generation to determine the marker alleles favorably associated to QTL alleles. The MAS was applied within family to young bulls, before progeny testing, as part of an open nucleus. Young bulls were selected using strategies based on 1) the single marker with greatest contrast (BEST1), 2) the sum of n greatest contrasts (BESTn), 3) the best n contrasts, limited to one per chromosome (LIMn), 4) the sum of all contrasts exceeding a given threshold n (THRESn), and 5) the sum of contrasts exceeding a threshold, but limited to one per chromosome (LIMT). The maximum progress was achieved by strategies that selected upon several markers flanking multiple QTL in each generation. When THRES was applied, the mean true breeding value (TBV) of selected bulls was increased by 11.98% (over conventional selection) versus 6.73% for BEST1 in the first generation. Applying a full genome scan in each generation allowed selection for different QTL across time. By selecting for multiple QTL over time, MAS maintained superiority over conventional selection for many generations.


The tyrosine phosphatase cdc25 selectively inhibits transcription of the Xenopus oocyte-type tRNAtyrC gene.
The Xenopus tyrosine tRNAtyrC (TyrC) genes are developmentally regulated. These multicopy genes are expressed in early oocytes and inactivated as oocytes reach maturity. As shown here, this developmental regulation can be reproduced in vitro in extracts of early and late stage oocytes: the TyrC gene is transcribed in early oocyte extracts but is virtually inactive in mature oocyte extracts. The inability to transcribe the TyrC gene is not due to the lack of functional pol III transcriptional components, since the somatic-type TyrD gene is fully active in mature oocyte extracts. Instead, the loss of TyrC transcription appears to be due to a change in the template specificity of transcription factor TFIIIC: addition of TFIIIC from immature extracts restores TyrC transcription in mature extracts. In mixtures of immature and mature extracts, the transcriptional activity of the TyrC gene is reduced. The presence of sodium vanadate, an inhibitor of tyrosine phosphatases, increases the level of TyrC transcription in the extract mixtures. Also, cdc25 phosphatase treatment of immature extracts causes a decrease in TyrC transcription which is reversed by addition of exogenous TFIIIC. These findings indicate that changes in phosphorylation state alters the template specificity of TFIIIC leading to the selective inactivation of oocyte type TyrC genes.


The clinical consequences of obstructive sleep apnea and associated excessive sleepiness.
Several conditions commonly seen in the primary care setting are known to be associated with obstructive sleep apnea (OSA), including hypertension, obesity, coronary artery disease, and type 2 diabetes, and should alert the physician to the possibility of this sleep disorder. The pathophysiology of OSA increases the risk of ischemic heart disease, decreases cardiac function, and elevates the risk of stroke. Treatment of OSA along with appropriate therapy for associated comorbidities presents an opportunity to simultaneously improve both conditions. Up to 56% of patients with OSA have hypertension. Addressing OSA can help improve this condition. More than 50% of patients with OSA experience depression. Treatment of OSA can lessen depressive symptoms associated with this sleeping disorder.


[Analysis on the variance of vacA genotypes and their vacuolating toxin activity of Helicobacter pylori isolates in Zhejiang area].
To analyze the variance of vacA genotypes and their vacuolating toxin activity of Helicobacter pylori (H. pylori) isolates from patients with peptic ulcer (PU) or chronic gastritis (CG) in Zhejiang area. Signal and middle regions of parts of seventy H. pylori strains were sequenced after T-A cloning. Vacuolating toxin activity was detected with cell culture method. Compared with the reported sequences of H. pylori strain 60190 with s1a/m1 genotype, similarities of the signal-region sequences from 6 s1a-type H. pylori isolates were found to be 93.2%-98.3%, and from 1 m1b-type strain was 87.3%. When compared with the corresponding sequences of H. pylori strain 87-203 with m2 genotype, similarities of the mid-region from 4 m2-type isolates and 1 m1b-type isolates were 93.8%-97.6% and 71.7%, respectively. All 5 strains with s1a/m1 type produced vacuolating toxin activity detected by HeLa, RK-13, and SGC-7901 cell lines. Only 12 strains with s1a/m2 type produced cytotoxin in HeLa cells but 65.1% (28/43) and 62.8% (27/43) strains had cytotoxin in RK-13 and SGC-7901 cells. In RK-13 cells, 81.0% (17/21) strains with s1a/m1b produced vacuolating toxin activity. Variance of vacA genotypes of local H. pylori isolates mainly lied in mid-region. H. pylori isolates with m2 type produced high cytotoxin in RK-13 and SGC-7901 cells, and low cytotoxin in HeLa cells. Cytotoxin strength of m1b-type strains was between strains with ml and m2 types. Vacuolating toxin activity of strains from PU group seemed obviously higher than that from CG group.


Treatment of postextubation stridor in a pediatric patient with burns: the role of heliox.
Stridor is a common problem in patients with burns after extubation, especially in children and in those with facial burns or airway injuries. The usual treatments for severe respiratory distress, such as reintubation and tracheotomy, carry substantial risks for patients. We report our successful treatment of severe postextubation stridor in a 7-year-old patient with burns with the administration of heliox in addition to more traditional therapies, review the literature about the use of heliox in postextubation stridor, and suggest cases in which its use may prevent the need for more hazardous interventions.


Similar Function and Improved Range of Shoulder Motion is Achieved Following Repair of Three- and Four-Part Proximal Humerus Fractures Compared with Hemiarthroplasty.
In order to compare open reduction and internal fixation (ORIF) with locked plating to hemiarthroplasty for the treatment of three- and four-part proximal humerus fractures, we compared two groups of patients treated during the same time period. Sixty-five patients who underwent repair of a three- or four-part proximal humerus fracture with locked plates (Group A) were identified in a prospective database and were compared to 29 patients who underwent hemiarthroplasty for similar injuries (Group B). Data was collected for both groups. Shoulder motion was measured and functional outcomes were obtained using the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. The mean length of follow-up for the ORIF group was 16 months compared to 44 months for the hemiarthroplasty group. The average postoperative forward flexion for patients in Group A was 131.1° and 110.4° for Group B (p < 0.047). There were no differences in DASH scores at latest follow-up (p = 0.64). Two patients in Group A had radiographic signs of osteonecrosis but had elected for no further surgery. One patient in Group A and two patients in Group B underwent a conversion to total shoulder arthroplasty. There was no difference in the rate of secondary surgery (p = 0.98). The results of this study suggest that ORIF using locked plates leads to similar postoperative function compared to hemiarthroplasty. Patients who underwent ORIF did achieve greater forward shoulder flexion. Neither strategy leads to a higher reoperation rate.


Biological and Social Determinants of Hypertension Severity Before vs After Intracerebral Hemorrhage.
Although blood pressure (BP) control is considered the most effective measure to prevent functional decline after intracerebral hemorrhage (ICH), fewer than half of survivors achieve treatment goals. We hypothesized that long-term (i.e., prehemorrhage) hypertension severity may be a crucial factor in explaining poor BP control after ICH. We investigated changes in hypertension severity after vs before ICH using latent class analysis (LCA) and identified patient characteristics predictive of individuals' BP trajectories. We analyzed data for ICH survivors enrolled in a study conducted at Massachusetts General Hospital (MGH) from 2002 to 2019 in Boston, a high-resource setting with near-universal medical insurance coverage. We captured BP measurements in the 12 months preceding and following the acute ICH hospitalization. Using LCA, we identified patient groups (classes) based on changes in hypertension severity over time in an unbiased manner. We then created multinomial logistic regression models to identify patient factors associated with these classes. Among 336 participants, the average age was 74.4 years, 166 (49%) were male, and 288 (86%) self-reported White race/ethnicity. LCA identified 3 patient classes, corresponding to minimal (n = 114, 34%), intermediate (n = 128, 38%), and substantial (n = 94, 28%) improvement in hypertension severity after vs before ICH. Survivors with undertreated (relative risk ratio [RRR] 0.05, 95% CI 0.01-0.23) or resistant (RRR 0.03, 95% CI 0.01-0.06) hypertension before ICH were less likely to experience substantial improvement afterwards. Residents of high-income neighborhoods were more likely to experience substantial improvement (RRR 1.14 per $10,000, 95% CI 1.02-1.28). Black, Hispanic, and Asian participants with uncontrolled hypertension before ICH were more likely to experience minimal improvement after hemorrhagic stroke (interaction p < 0.001). Most ICH survivors do not display consistent improvement in hypertension severity after hemorrhagic stroke. BP control after ICH is profoundly influenced by patient characteristics predating the hemorrhage, chiefly prestroke hypertension severity and socioeconomic status. Neighborhood income was associated with hypertension severity after ICH in a high-resource setting with near-universal health care coverage. These findings likely contribute to previously documented racial/ethnic disparities in BP control and clinical outcomes following ICH.


What controls the magnetic anisotropy in heptacoordinate high-spin cobalt(II) complexes? A theoretical perspective.
The magnetic anisotropy of sixteen seven-coordinate high-spin CoII complexes with O, N, Cl and I donors was investigated with state-of-the-art ab initio CASSCF/NEVPT2 calculations and compared with experimental data. Based on the nature of the equatorial and axial ligands, which were found to tune the zero-field splitting, the complexes were classified into four groups. The experimental zero-field splitting parameters D which, for the various structures are in a range of +30 to +60 cm-1, as well as the g and E values are well reproduced. The investigation of the electronic structure shows that in these pentagonal bipyramidal complexes the donors and symmetry in the equatorial plane play an important role in the values of the axial zero-field splitting parameter D, and breaking of the horizontal plane of symmetry was found to enhance the magnitude of the D value. Although negative values of D are a desired condition for SIMs, many CoII based SIMs with positive zero-field splitting are fundamentally important to understand the nature of magnetic anisotropy, and seven coordinate CoII complexes with a large overall crystal field splitting might provide a way forward in this class of molecules.


Optimal flexible laryngeal mask airway size in children weighing 10 to 20 kg.
This prospective, randomised study was conducted to assess the effect of flexible laryngeal mask airway (FLMA) size on oropharyngeal leak pressure (OLP) in children at the recommended intracuff pressure. A total of 120 children undergoing elective ophthalmic surgery were randomly assigned to the size 2 FLMA group or size 2.5 FLMA group. The primary measurement was OLP at an intracuff pressure of 40 cmH2O. Secondary outcomes included the incidence of OLP <10 cmH2O, insufficient ventilation, gastric insufflation, insertion time, successful first-attempt insertion rate, fibreoptic view grade and pharyngolaryngeal adverse events. The median OLP was comparable for the size 2 and size 2.5 FLMA (18 cmH2O versus 18 cmH2O, P=0.38). However, the size 2 FLMA group had a higher incidence of OLP <10 cmH2O and insufficient ventilation (13.3% versus 0, P=0.006). In subgroup analyses based on weight, the size 2.5 FLMA had a lower occurrence of OLP <10 cmH2O and insufficient ventilation (27% versus 0, P=0.0046) in children 16-20 kg. We conclude that at a 40 cmH2O intracuff pressure, the OLP with the size 2 and size 2.5 FLMA was similar in children weighing 10-15.9 kg. However, in children weighing 16-20 kg, size 2 devices had a higher incidence of low OLP and insufficient ventilation, so a 2.5 FLMA may be preferable in this subgroup.


Omission after admission: failure in prescribed medications being given to inpatients.
Prescribing errors are a recognised problem on admission to acute medical wards which may be detrimental to patient care. The authors had anecdotal evidence that prescribed medicines do not always reach patients and the aim of this audit was to quantify this problem. Admission prescription charts on two separate occasions were studied in detail and all drugs prescribed but not given in the first 48 hours were recorded along with the reason given for omission. In total, 271 patient charts were analysed. Of these, 20% of prescriptions affecting 17% of patients did not reach patients. The two dominant reasons for medications not being given to patients were that the medication was not available on the ward (38% of omissions) or that the patient was nil by mouth (32% of omissions). In 10% of cases the patient refused the medication, in 19% no reason for omission was given and in only a minority (0.3%) was the patient off the ward. This audit demonstrates that even when medications are prescribed they are not always given. This may lead to increased morbidity and length of stay. Strategies need to be put in place to reduce this problem. The current system that permits omission of medications with inadequate justification must be revised.


Extraskeletal osteochondroma near the hip: a pediatric case.
Extraskeletal osteochondroma near the hip is rare and its pathological diagnosis is based on radiological and histopathological examination. It is vital that such a diagnosis be considered when a discrete, ossified mass is localized in soft tissues, even at atypical sites. Differential diagnoses include myositis ossificans, a lipomatous lesion, a pseudomalignant osseous tumour, an ossifying fibromyxoid tumour, an extraskeletal chondroma with endochondral ossification, synovial (osteo) chondromatosis, tumoural calcinosis, a synovial sarcoma and an extraskeletal osteosarcoma. Clinical awareness of this benign entity is important as no malignant transformation or metastasis has been reported. Marginal excision with histopathological identification is the treatment of choice.


Species-dependent degradation of ciprofloxacin in a membrane anodic Fenton system.
The anodic Fenton treatment method (AFT) has been successfully applied to the removal of ciprofloxacin (CIP), a widely used fluoroquinolone antibiotic, from aqueous solution. Degradation kinetics were found to be species dependent. At initial pH 3.2, CIP remained in its cationic form and the kinetics followed a previously developed AFT model. At an initial near-neutral pH, CIP speciation changed during the degradation, due to pH changes over the process, and no obvious model fit the data. Density functional theory (DFT) calculations indicated a protonated species-dependent reaction affinity toward hydroxyl radicals. A new model based on the AFT model with the addition of species distribution during the degradation was derived, and it was shown to describe the degradation kinetics successfully. Degradation of reference compounds further confirmed that the free carboxylic acid group, which contributes to the species changes, plays a key role in the observed degradation pattern. Furthermore, degradation of reference CIP-metal complexes confirmed that the formation of these complexes does not have a major effect on the degradation pattern. Optimization of CIP degradation was carried out at pH 3.2 with an optimal H2O2/Fe2+ ratio found between 10:1 and 15:1. Three degradation pathways based on mass spectrometry data were also proposed: (1) hydroxylation and defluorination on the aromatic ring; (2) oxidative decarboxylation; and (3) oxidation on the piperazine ring and dealkylation. By the end of the AFT treatment, neither CIP nor its degradation products were detected, indicating successful removal of antibacterial properties.


Pentoxifylline improves bacterial clearance during hemorrhage and endotoxemia.
The aim of this study was to investigate whether the methylxanthine-derivative pentoxifylline (PTX) affects bacterial clearance of the organism in states of hemorrhage and endotoxemia. Prospective, randomized, controlled trial. Experimental laboratory in a university hospital. Fifty-four female chinchilla rabbits. To quantify the clearance process, defined numbers (10(7) CFO) of Escherichia coli bacteria were injected intravenously into anesthetized rabbits, 60 mins after induction of hemorrhage (n = 9 + 3) or infusion of endotoxin (lipopolysaccharide [LPS]; 40 microg/kg/hr; n = 9 + 3) and after saline infusion (control; n = 9), respectively. Hemorrhage was induced by bleeding, standardized by defined reduction of mean arterial pressure (30% of baseline value). To evaluate the potential effects of PTX on bacterial elimination and killing, in states of hemorrhage and endotoxemia, blood clearance of E. coli and colonization of different organs were investigated after pretreatment with PTX (30 mg/kg) as a bolus injection followed by continuous infusion of PTX (50 mg/kg/hr) in hemorrhagic (n = 9) and endotoxemic rabbits (n = 9). Three additional experiments were performed to evaluate the effects attributable to PTX itself. Parameters monitored were rates of bacterial and LPS elimination from the blood, arterial blood pressure, blood gases, and serum lactate concentrations. Additionally, flow cytometric analysis of respiratory burst activity was performed. Three hours after bacterial injection, the animals were killed, and tissue samples of liver, kidney, spleen, and lung were collected for bacteriologic examinations. Compared with the controls, hemorrhage and endotoxemia resulted in a significantly prolonged elimination of injected E. coli from the blood. The delayed blood clearance was associated with a significantly (p < .01) higher bacterial colonization of all organs, which was most pronounced in the lung. Pretreatment with PTX slightly enhanced blood clearance of E. coli as well as of LPS, and significantly reduced (p < .05) the colonization of lung and kidney after hemorrhage and endotoxemia. Furthermore, PTX suppressed polymorphonuclear neutrophil respiratory burst activity. Hemorrhage and endotoxemia induce impaired bacterial clearance from blood and tissue. Treatment with PTX may reduce the risk of bacterial infections by attenuating bacterial colonization of organs in states of hemorrhage and endotoxemia.


[Detection of glaucoma using SisGlaTel: acceptability and satisfaction among participants, and problems detected].
To evaluate the problems, and the degree of acceptability and satisfaction among participants in a telemedicine screening program. This study forms part of a global project for the design, implementation and evaluation of SisGlaTel funded by the Fondo de Investigaciones Sanitarias (Spain) and Pfizer Ophthalmics. A telemedicine system was built based on a specific program written in JAVA. The remote station was located at a Primary Care Center. Participants signed an informed consent, and completed a questionnaire and undertook different tests (frequency doubling perimetry-FDT, confocal scanning laser tomografy-HRT and tonometry). Test results and problems detected were analysed. Ninety-nine subjects completed a satisfaction questionnaire after voluntarily participating in the screening program among an at-risk population. The questionnaire included 7 questions, four of which required participants to categorise their responses, ranging from very bad (1) to excellent (5), to questions about the screening program, its usefulness, the care received and the installations. Six hundred and forty-one at-risk subjects were examined. After 2 exams per eye, 22.3% (143) presented abnormal FDT and 4.2% (27) had pathologic HRT. One hundred percent of respondents affirmed they would participate again in a similar program. The mean qualification (SD) was 4.5 (0.6), 4.5 (0.6), 4.8 (0.5), and 4.3 (0.7) for global opinion, usefulness, care and equipment. SisGlaTel allows integration of several diagnostic tests useful for glaucoma tele-screening. The global degree of satisfaction among participants was good.


Juvenile Behçet's disease in Arab children.
Behçet's disease is a chronic, relapsing, multisystem disease characterized by the clinical triad of genital ulcers, oral ulcers and ocular involvement. Twelve Saudi children are presented, all of whom satisfied the international criteria for the classification of Behçet's disease and whose initial manifestations appeared at or before the age of 16 years. The male-to-female ratio was 1.4:1. The mean age at onset was 11.5 years (range 7-16 years) and the mean duration of disease was 6.5 years (range 3-13 years). Oral ulcers were present in all patients (100%), genital ulcers in 11 patients (91%), ocular involvement in the form of anterior and/or posterior uveitis in 6 patients (50%), skin manifestations in 10 patients (83%), musculoskeletal symptoms in 9 patients (75%), and central nervous system involvement in 6 patients (50%). One patient had thrombophlebitis and another had pulmonary artery aneurysm. No renal, cardiovascular or gastrointestinal abnormalities were detected. The pathergy test was positive in 3/7 patients. HLA B5 (W51) typing was positive in 5/10 patients. This report of juvenile Behçet's disease in Saudi children suggests that this multisystem disease has an aggressive nature and should be considered in the differential diagnosis of childhood vasculitis in endemic areas.


An Invertible Mathematical Model of Cortical Bone's Adaptation to Mechanical Loading.
Determination of mechanical loading regimen that would induce a prescribed new bone formation rate and its site-specific distribution, may be desirable to treat some orthopaedic conditions such as bone loss due to muscle disuse, e.g. because of space flight, bed-rest, osteopenia etc. Site-specific new bone formation has been determined earlier experimentally and numerically for a given loading regimen; however these models are mostly non-invertible, which means that they cannot be easily inverted to predict loading parameters for a desired new bone formation. The present work proposes an invertible model of bone remodeling, which can predict loading parameters such as peak strain, or magnitude and direction of periodic forces for a desired or prescribed site-specific mineral apposition rate (MAR), and vice versa. This fast, mathematical model has a potential to be developed into an important aid for orthopaedic surgeons for prescribing exercise or exogenous loading of bone to treat bone-loss due to muscle disuse.


Intestinal alkaline phosphatase: regulation by a strain-specific factor in mouse milk.
Two inbred strains of mice show a threefold difference in duodenal phosphatase activity at 11 days of age. When half-litters of the two strains are interchanged between the two mothers on the day of birth, enzyme activity in young of the low-activity strain is unaffected at 11 days by the source of milk, but is significantly reduced in high-activity young nursed by a low-activity mother.


Management of postpneumonectomy empyema and bronchopleural fistula.
Postpneumonectomy empyema with or without fistula is a serious complication. Management includes drainage, antibiotherapy, debridement closure of the bronchopleural fistula when present, and obliteration of the residual pleural space. Excellent results can be obtained in most patients using the Clagett procedure and its modification. A detailed description of each step of the surgical treatment of postpneumonectomy empyema and associated bronchopleural fistula is provided.


[Chronic heart failure].
As a consequence of the increasing life expectancy the number of patients suffering from chronic heart failure has been growing continuously in the past few decades, especially in the group of the old and oldest. Frailty is a clinical syndrome that geriatricians attach great importance to. Like many other diseases chronic heart failure can cause frailty. Based on the experience that we see only a small correlation between the functional capacity of patients with heart failure and the results of cardiological findings, the model of peripheral myopathy in chronic heart failure was developed. Different pathophysiological changes may cause the increasing exercise intolerance in patients with chronic heart failure. We can already consider different experimental approaches to the therapy of frailty caused by chronic heart failure. At the moment we have to focus our efforts on an optimal therapy of heart failure, especially with angiotensin-converting-enzyme inhibitors and beta-blockers, and on individual endurance and strength training.