Telemonitoring with an implantable loop recorder in outpatient heart failure care : One year follow-up report from a prospective observational Dutch multicentre study.

INTRODUCTION: In the care of heart failure patients, telemonitoring is receiving growing attention. The main purpose of this study was to determine the effect of continuous telemonitoring with an implantable loop recorder (ILR, Reveal XT), a novel strategy in the management of stable heart failure patients without a cardiac implantable device. Furthermore, little is known about the incidence of subclinical arrhythmias in this specific group of patients. MATERIALS AND METHODS: Stable heart failure patients, New York Heart Association Class II and III, without recent hospitalisation or upcoming intervention, were included. After implantation of the ILR there was regular contact with the research nurse on a pre-specified basis. Clinic visits and telephonic interviews were alternated for a minimum of 1 year. Parallel visits to their treating physician continued according to standard care. The treating physician was blinded for the ILR findings, accept for pre-specified, significant arrhythmic events. RESULTS: Thirty patients were included and followed for a median duration of 12 months. In 13 patients, data from the loop recorder led to therapeutic changes. One patient received a pacemaker. Eight patients developed atrial fibrillation, all subclinical, with a mean burden of 65.8 ± 173.2 min/day. CONCLUSION: The use of an ILR could potentially impact patient management. Additional study is needed in different patient populations (e. g. higher risk groups) to assess if an ILR could also impact on endpoints such as heart failure hospitalisation.

Expanding the reach of probiotics through social enterprises.

The rapid rise in microbiome and probiotic science has led to estimates of product creation and sales exceeding $50 billion within five years. However, many people do not have access to affordable products, and regulatory agencies have stifled progress. The objective of a discussion group at the 2017 meeting of the International Scientific Association for Probiotics and Prebiotics was to identify mechanisms to confer the benefits of probiotics to a larger portion of the world's population. Three initiatives, built around fermented food, were discussed with different methods of targeting populations that face enormous challenges of malnutrition, infectious disease, poverty and violent conflict. As new candidate probiotic strains emerge, and the market diversifies towards more personalised interventions, manufacturing processes will need to evolve. Information dissemination through scientific channels and social media is projected to provide consumers and healthcare providers with rapid access to clinical results, and to identify the nearest location of sites making new and affordable probiotic food and supplements. This rapid translation of science to individual well-being will not only expand the beneficiaries of probiotics, but also fuel new social enterprises and economic business models.

Germination inhibition of Bacillus cereus spores: impact of the lipophilic character of inhibiting compounds.

In this study, the impact of a range of organic acids and structurally similar alcohols with three to six carbon backbones and increasing lipophilic character, were tested on the germination behavior of B. cereus ATCC 14579 spores. This approach allowed substantiating whether the effectivity of the various compounds was largely dictated by membrane interference or a classic weak acid acidification effect. The octanol-water partition coefficient (log P(oct/water)) ranges from 0.25/0.33 to 2.03/1.96 for propanol/undissociated propionic acid and hexanol/undissociated hexanoic acid, respectively. Performance of germination assays at neutral (pH7) and acidic conditions (pH5.5) allowed for a comparative analysis of the action of dissociated versus undissociated acids, and the presumed pH-independent effect of the corresponding alcohols. Germination assays, based on both continuously measured optical density and time-based plating experiments, and microscopic observations demonstrated the correlation between the lipophilic character of the selected compounds and their inhibiting effect on spore germination. Real-time fluorescence based assays showed that membrane integrity in dormant spores was maintained in the presence of the tested inhibitors. Lowering the critical concentration of inhibitors by a one-step washing procedure resulted in the onset of nutrient-induced germination, indicating the reversible nature of the inhibition process. Furthermore, blocking of nutrient-induced germination in the presence of inhibitory concentrations of selected lipophilic acids and corresponding alcohols was by-passed upon addition of Ca-dipicolinic acid, pointing to loss of signaling capacity in germinant receptor-mediated germination activity. These findings show that lipophilicity is an important determinant for the ability of the selected acids and corresponding alcohols to accumulate in the spore inner membrane and their ability to act as a germination-inhibitor.

[Transient pustular eruption in neonates]. / Mélanose pustuleuse néonatale transitoire.

Transient neonatal pustular melanosis is a common, benign, but little known dermatosis in newborns. Diagnosis of transient neonatal pustular melanosis is made clinically, by the presence of vesiculopustular and pigmented macular skin lesions. This benign spontaneously regressive dermatosis should be distinguished from several serious infectious neonatal diseases. We report a case of transient neonatal pustular melanosis and discuss the nosologic problems and differential diagnosis of this entity.

Modelling the effect of sub(lethal) heat treatment of Bacillus subtilis spores on germination rate and outgrowth to exponentially growing vegetative cells.

Spores of Bacillus subtilis were subjected to relatively mild heat treatments in distilled water and properties of these spores were studied. These spores had lost all or part of their dipicolinic acid (DPA) depending on the severity of the heat treatment. Even after relatively mild heat treatments these spore lost already a small but significant amount of DPA. When these spores were inoculated in nutrient medium-tryptone soy broth (TSA)-the non-lethally heated spores started to germinate. Results of classical optical density measurements showed that both phase darkening and subsequent outgrowth could be affected by sub-lethal heat. A study of single cells in TSB showed that lag times originating from exponentially growing cells followed a normal distribution, whereas lag times originating from spores followed a Weibull distribution. Besides classical optical density measurements were made to study the effect of previous heating on the kinetics of the first stages of germination. The germination kinetics could be described by the model as was proposed by Geeraerd et al. [Geeraerd, A.H., Herremans, C.H. and Van Impe, J.F., 2000. Structural model requirements to describe microbial inactivation during a mild heat treatment. International Journal of Food Microbiology 59, 185-209]. Two of the 4 parameters of the sigmoid model of Geeraerd were dependent on heating time and heating temperature, whereas the two other parameters were considered as independent of the heating conditions. Based on these observations, a secondary model could be developed that describes the combined effect of heating temperature and heating time on the kinetics of germination. To have more detailed information of the kinetics of germination samples incubated in TSB were tested at regular time intervals by flow cytometry. To that end the cells were stained with syto 9 to distinguish between the various germination stages. There was a qualitative agreement between the results of flow cytometry and those of optical density measurements, but there was a difference in quantitative terms. The results have shown that germination rate of spores is dependent on previous heating conditions both in the first stage when phase darkening occurs and also during the later stages of outgrowth when the phase dark spore develops to the vegetative cell.

Use of simulation mass balance modeling to estimate phosphorus and bacteria dynamics in watersheds.

Dynamic simulation technology is integrated with mass balance concepts and compartment-flux diagramming to create computer models that estimate contaminant export from watersheds over long and short-term futures under alternative simulated policies of watershed management. The Watershed Ecosystem Nutrient Dynamics (WEND) model, applied to developed watersheds with a mix of urban, agricultural, and forest land-uses, predicted phosphorus (P) export from three watersheds; a 275,000 ha dairy/urban watershed, a 77,000 ha poultry/urban watershed, and a 23,000 ha swine dominated watershed. Urban, agricultural, and forestry activities contribute to P export in different proportions. In all cases the P imports to the watershed exceed total export and P accumulates in watershed soils. Long-term future P export patterns are compared for several watershed management strategies that range from encouragement of rapid urban growth to aggressive environmental protection. The specific response of each watershed to imposed management is unique, but management strategies designed to reduce export of P over the long-term need to consider options that promote P input/output balance. Using this same approach, the Watershed Ecosystem Bacterial Dynamics (WEBD) model assesses the dynamics of bacterial populations in a small case-study watershed over an annual cycle as influenced by dairy farm management actions. WEND and WEBD models integrate the diversity of activities and stakeholders interested in the watershed and promote development of a more holistic understanding of watershed function. Model outputs are designed to assist watershed policy-makers, managers, and planners to explore potential future impacts of management/policy decisions.

[Multiple keratoacanthoma centrifugum marginatum]. / Kératoacanthomes centrifuges marginés multiples.

INTRODUCTION: Keratoacanthoma centrifugum marginatum is a rare variety of commonly isolated keratoacanthoma. The size of the lesions and prolonged evolution often raise therapeutic problems. CASE REPORT: A 63-year-old man presented with multiple keratoacanthoma centrifugum marginatum evolving for 6 months and predominating on the lower limbs. Because of the multiplicity and size of the lesions, the patient was treated at acitretine at the dose of 1 mg/kg/day for five months, leading to the regression of all the lesions. DISCUSSION: Keratoacanthoma centrifugum marginatum has rarely been reported in the literature. Our observation remains exceptional in the multiplicity and size of the lesions. The efficacy of retinoids, previously reported in the treatment of solitary giant keratoacanthoma, multiple keratoacanthoma and keratoacanthoma centrifugum marginatum, was demonstrated even in this handicapping form of keratoacanthoma.

Real-space imaging of an orbital Kondo resonance on the Cr(001) surface.

The Kondo effect is usually connected with the interaction between a localized spin moment and itinerant electrons. This interaction leads to the formation of a narrow resonance at the Fermi level, which is called the Abrikosov-Suhl or Kondo resonance. Scanning tunnelling microscopy is an ideal technique for real-space investigations of complicated electronic structures and many-body phenomena, such as the formation of the Kondo resonance or d-wave pairing in high-T(c) superconductors. Theory has predicted that similar, Kondo-like many-electron resonances are possible for scattering centres with orbital instead of spin degrees of freedom--the quadruple momenta in uranium-based compounds or two-level systems in metallic glasses are examples of such 'pseudo-Kondo' scattering centres. Here we present evidence for the orbital Kondo resonance on a transition-metal surface. Investigations of an atomically clean Cr(001) surface at low temperature using scanning tunnelling microscopy reveal a very narrow resonance at 26 meV above the Fermi level, and enable us to visualize the orbital character of the corresponding state. The experimental data, together with many-body calculations, demonstrate that the observed resonance is an orbital Kondo resonance formed by two degenerate d(xz), d(yz) surface states.

A molecular movie at 1.8 A resolution displays the photocycle of photoactive yellow protein, a eubacterial blue-light receptor, from nanoseconds to seconds.

The photocycle of the bacterial blue-light photoreceptor, photoactive yellow protein, was stimulated by illumination of single crystals by a 7 ns laser pulse. The molecular events were recorded at high resolution by time-resolved X-ray Laue diffraction as they evolved in real time, from 1 ns to seconds after the laser pulse. The complex structural changes during the photocycle at ambient temperature are displayed in a movie of difference electron density maps relative to the dark state. The step critical to entry into the photocycle is identified as flipping of the carbonyl group of the 4-hydroxycinnamic acid chromophore into an adjacent, hydrophobic environment rather than the concomitant isomerization about the double bond of the chromophore tail. The structural perturbation generated at the chromophore propagates throughout the entire protein as a light-induced "protein quake" with its "epicenter" at the carbonyl moiety of the chromophore.

Alkalispirillum mobile gen. nov., spec. nov., an alkaliphilic non-phototrophic member of the Ectothiorhodospiraceae.

From cultures of the anoxygenic phototroph Halorhodospira halophila SL-1, an aerobic, gram-negative spirillum was isolated. This moderately halophilic, alkaliphilic bacterium was motile by means of a single polar flagellum. It is described here as Alkalispirillum mobile gen. nov., spec. nov. Phylogenetic analysis of the Alkalispirillum mobile 16S rRNA gene led to its classification in the gamma-subclass of the Proteobacteria, as it appears closely related to phototrophic purple sulfur bacteria of the genera Ectothiorhodospira and Halorhodospira. Surprisingly, A. mobile is an obligate aerobe. The organism grows optimally with a number of carboxylic acids (such as sodium acetate) as carbon source, at 2% (i.e. approximately 0.34 M) sodium chloride, at pH 9-10, and at temperatures ranging from 35 to 38 degrees C. The dominant cellular fatty acids of Alkalispirillum mobile are C12:0, C16:0, C18:1cis11, and C18:0; its G+C content is 66.2+/-0.5 mol%.

Dynamic phosphorus mass balance modeling of large watersheds: long-term implications of management strategies.

The principles of mass balance, compartment-flux diagramming, and dynamic simulation modeling are integrated to create computer models that estimate phosphorus (P) export from large-scale watersheds over long-term futures. These Watershed Ecosystem Nutrient Dynamics (WEND) models are applied to a 275,000 ha dairy-documented watershed and a 77,000 ha poultry-dominated watershed in northeastern USA. Model predictions of present-day P export loads are consistent with monitoring data and estimates made using P export coefficients. For both watersheds P import exceeds P export and P is accumulating in the agricultural soils. Agricultural and urban activities are major contributors to P export from both watersheds. Continued urban growth will increase P export over time unless wastewater management is substantially enhanced and/or rates of urban growth are controlled. Agriculture cannot rely solely on the implementation of increasingly stringent conservation practices to reduce long-term P export but must consider options that promote P input/output balance. The WEND modeling process is a powerful tool to integrate the diversity of activities in watersheds into a holistic framework. Model outputs are suited to assist managers to explore long-term effects of overall watershed management strategies on P export in comparison to environmental and economic goals.

Color-sensitive motility and methanol release responses in Rhodobacter sphaeroides.

Blue-light-induced repellent and demethylation responses, characteristic of behavioral adaptation, were observed in Rhodobacter sphaeroides. They were analyzed by computer-assisted motion analysis and through the release of volatile tritiated compounds from [methyl-(3)H]methionine-labeled cells, respectively. Increases in the stop frequency and the rate of methanol release were induced by exposure of cells to repellent light signals, such as an increase in blue- and a decrease in infrared-light intensity. At a lambda of >500 nm the amplitude of the methanol release response followed the absorbance spectrum of the photosynthetic pigments, suggesting that they function as photosensors for this response. In contrast to the previously reported motility response to a decrease in infrared light, the blue-light response reported here does not depend on the number of photosynthetic pigments per cell, suggesting that it is mediated by a separate sensor. Therefore, color discrimination in taxis responses in R. sphaeroides involves two photosensing systems: the photosynthetic pigments and an additional photosensor, responding to blue light. The signal generated by the former system could result in the migration of cells to a light climate beneficial for photosynthesis, while the blue-light system could allow cells to avoid too-high intensities of (harmful) blue light.

Trans/cis (Z/E) photoisomerization of the chromophore of photoactive yellow protein is not a prerequisite for the initiation of the photocycle of this photoreceptor protein.

The chromophore of photoactive yellow protein (PYP) (i.e., 4-hydroxycinnamic acid) has been replaced by an analogue with a triple bond, rather than a double bond (by using 4-hydroxyphenylpropiolic acid in the reconstitution, yielding hybrid I) and by a "locked" chromophore (through reconstitution with 7-hydroxycoumarin-3-carboxylic acid, in which a covalent bridge is present across the vinyl bond, resulting in hybrid II). These hybrids absorb maximally at 464 and 443 nm, respectively, which indicates that in both hybrids the deprotonated chromophore does fit into the chromophore-binding pocket. Because the triple bond cannot undergo cis/trans (or E/Z) photoisomerization and because of the presence of the lock across the vinyl double bond in hybrid II, it was predicted that these two hybrids would not be able to photocycle. Surprisingly, both are able. We have demonstrated this ability by making use of transient absorption, low-temperature absorption, and Fourier-transform infrared (FTIR) spectroscopy. Both hybrids, upon photoexcitation, display authentic photocycle signals in terms of a red-shifted intermediate; hybrid I, in addition, goes through a blue-shifted-like intermediate state, with very slow kinetics. We interpret these results as further evidence that rotation of the carbonyl group of the thioester-linked chromophore of PYP, proposed in a previous FTIR study and visualized in recent time-resolved x-ray diffraction experiments, is of critical importance for photoactivation of PYP.

Sequence, chromophore extraction and 3-D model of the photoactive yellow protein from Rhodobacter sphaeroides.

The photoactive yellow protein (pyp) gene has been isolated from Rhodobacter sphaeroides by probing with a homologous PCR-product. A sequence analysis shows that this pyp gene encodes a 124 AA protein with 48% identity to the three known PYPs. Downstream from pyp, a number of adjacent open reading frames were identified, including a gene encoding a CoA-ligase homologue (pCL). This latter protein is proposed to be involved in PYP chromophore activation, required for attachment to the apoprotein. We have demonstrated the presence of the chromophoric group, previously identified in PYP from Ectothiorhodospira halophila as trans 4-hydroxy cinnamic acid, in phototrophically cultured R. sphaeroides cells by capillary zone electrophoresis. The basic structure of the chromophore binding pocket in PYP has been conserved, as shown by a 3D model of R. sphaeroides PYP, constructed by homology-based molecular modelling. In addition, this model shows that R. sphaeroides PYP contains a characteristic, positively charged patch.

Energy transduction on the nanosecond time scale: early structural events in a xanthopsin photocycle.

Photoactive yellow protein (PYP) is a member of the xanthopsin family of eubacterial blue-light photoreceptors. On absorption of light, PYP enters a photocycle that ultimately transduces the energy contained in a light signal into an altered biological response. Nanosecond time-resolved x-ray crystallography was used to determine the structure of the short-lived, red-shifted, intermediate state denoted [pR], which develops within 1 nanosecond after photoelectronic excitation of the chromophore of PYP by absorption of light. The resulting structural model demonstrates that the [pR] state possesses the cis conformation of the 4-hydroxyl cinnamic thioester chromophore, and that the process of trans to cis isomerization is accompanied by the specific formation of new hydrogen bonds that replace those broken upon excitation of the chromophore. Regions of flexibility that compose the chromophore-binding pocket serve to lower the activation energy barrier between the dark state, denoted pG, and [pR], and help initiate entrance into the photocycle. Direct structural evidence is provided for the initial processes of transduction of light energy, which ultimately translate into a physiological signal.

Current topics in signal transduction in bacteria.

Among the signal transfer systems in bacteria two types predominate: two-component regulatory systems and quorum sensing systems. Both types of system can mediate signal transfer across the bacterial cell envelope; however, the signalling molecule typically is not taken up into the cells in the former type of system, whereas it usually is in the latter. The Two-component systems include the recently described (eukaryotic) phosphorelay systems; quorum sensing systems can be based upon autoinducers of the N-acylated homoserine lactones, and on autoinducers of a peptidic nature. A single bacterial cell contains many signalling modules that primarily operate in parallel. This may give rise to neural-network behaviour. Recently, however, for both types of basic signal transfer modules, it has been demonstrated that they also can be organised in series (i.e. in a hierarchical order). Besides their hierarchical position in the signal transduction network of the cell, the spatial distribution of individual signalling modules may also be an important factor in their efficiency in signal transfer. Many challenges lie hidden in future work to understand these signal transfer processes in more detail. These are discussed here, with emphasis on the mutual interactions between different signal transfer processes. Successful contributions to this work will require rigorous mathematical modelling of the performance of signal transduction components, and -networks, as well as studies on light-sensing signal transduction systems, because of the unsurpassed time resolution obtainable in those latter systems, the opportunity to apply repeated reproducible stimuli, etc. The increased understanding of bacterial behaviour that already has resulted--and may further result--from these studies, can be used to fine-tune the beneficial activities of bacteria and/or more efficiently inhibit their deleterious ones.

Glutamate dehydrogenase from the hyperthermophilic bacterium Thermotoga maritima: molecular characterization and phylogenetic implications.

The hyperthermophilic bacterium Thermotoga maritima, which grows at up to 90 degrees C, contains an L-glutamate dehydrogenase (GDH). Activity of this enzyme could be detected in T. maritima crude extracts, and appeared to be associated with a 47-kDa protein which cross-reacted with antibodies against purified GDH from the hyperthermophilic archaeon Pyrococcus woesei. The single-copy T. maritima gdh gene was cloned by complementation in a glutamate auxotrophic Escherichia coli strain. The nucleotide sequence of the gdh gene predicts a 416-residue protein with a calculated molecular weight of 45,852. The gdh gene was inserted in an expression vector and expressed in E. coli as an active enzyme. The T. maritima GDH was purified to homogeneity. The NH2-terminal sequence of the purified enzyme was PEKSLYEMAVEQ, which is identical to positions 2-13 of the peptide sequence derived from the gdh gene. The purified native enzyme has a size of 265 kDa and a subunit size of 47kDa, indicating that GDH is a homohexamer. Maximum activity of the enzyme was measured at 75 degrees C and the pH optima are 8.3 and 8.8 for the anabolic and catabolic reaction, respectively. The enzyme was found to be very stable at 80 degrees C, but appeared to lose activity quickly at higher temperatures. The T. maritima GDH shows the highest rate of activity with NADH (Vmax of 172 U/mg protein), but also utilizes NADPH (Vmax of 12 U/mg protein). Sequence comparisons showed that the T. maritima GDH is a member of the family II of hexameric GDHs which includes all the GDHs isolated so far from hyperthermophiles. Remarkably, phylogenetic analysis positions all these hyperthermophilic GDHs in the middle of the GDH family II tree, with the bacterial T. maritima GDH located between that of halophilic and thermophilic euryarchaeota.