Alpha-thalassaemia and response to hydroxyurea in sickle cell anaemia.
Hydroxyurea (HU) reduces vaso-occlusive crises (VOC) and other complications of sickle cell anaemia (SCA). Alpha-thalassaemia is a known modifier of SCA. Studies on the efficacy of HU in SCA patients with α-thalassaemia have yielded varying results. To determine the effect of α-thalassaemia in response to HU therapy in the Multicenter Study of Hydroxyurea (MSH) cohort. We compared the laboratory parameters and VOC incidence in the MSH cohort stratified by the presence or the absence of α-thalassaemia. Hydroxyurea showed significant (P = 0.001 for all baseline vs. follow-up comparisons) treatment effect on red cell indices irrespective of α-globin gene deletion. The magnitude of the HU-related changes was similar for mean corpuscular volume (MCV) (no α-thalassaemia 13 fl and α-thalassaemia 13 fl) and mean corpuscular haemoglobin (MCH) (no α-thalassaemia 4 pg and α-thalassaemia 4 pg) in both groups. Foetal haemoglobin (HbF) and F-cells also increased significantly with HU treatment in both groups. Total haemoglobin increased after HU treatment in both groups, but the increase was smaller and not statistically significant in patients with α-thalassaemia. In contrast, HU-related reduction in VOCs was more pronounced in patients with α-thalassaemia (VOC incidence rate ratio HU/placebo: 0.63 for α-thalassaemia and 0.54 for no α-thalassaemia (P for interaction 0.003). Hydroxyurea decreases VOCs in SCA patients with and without α-thalassaemia, and the degree of VOC reduction was more pronounced in the patients with alpha-thalassaemia. Despite the lower baseline values, changes in standard laboratory parameters such as MCV and HbF percent remain useful in monitoring HU therapy in the presence of α-thalassaemia.


[Osteoarthritis: etiology, risk factors, molecular mechanisms].
Osteoarthritis is an incurable joint disease manifesting itself with gradually progressing degenerative changes, leading to premature motor disability. These changes mainly occur owing to an imbalance between the processes of degeneration and regeneration of articular cartilage structures. Until now many risk factors favoring the development of degenerative joint disease have been identified. These include age, weight, previously sustained traumas to joints, sports, sex and genetic predisposition. The latest scientific reports confirm that the pathogenesis of changes in osteoarthritic joints is complex and occurs on many levels. Enzymes belonging to the metalloproteinases family are mainly responsible for the degeneration of articular cartilage. Their activity is regulated by numerous pro-inflammatory cytokines, transcription factors and miRNA. A thorough analysis of all processes occurring in the afflicted joints needs to be carried out before effective therapeutic strategies can be developed.


Microfluidics and Metabolomics Reveal Symbiotic Bacterial-Fungal Interactions Between Mortierella elongata and Burkholderia Include Metabolite Exchange.
We identified two poplar (Populus sp.)-associated microbes, the fungus, Mortierella elongata strain AG77, and the bacterium, Burkholderia strain BT03, that mutually promote each other's growth. Using culture assays in concert with a novel microfluidic device to generate time-lapse videos, we found growth specific media differing in pH and pre-conditioned by microbial growth led to increased fungal and bacterial growth rates. Coupling microfluidics and comparative metabolomics data results indicated that observed microbial growth stimulation involves metabolic exchange during two ordered events. The first is an emission of fungal metabolites, including organic acids used or modified by bacteria. A second signal of unknown nature is produced by bacteria which increases fungal growth rates. We find this symbiosis is initiated in part by metabolic exchange involving fungal organic acids.


Polarity-sensitive transient patterned state in a twisted nematic liquid crystal driven by very low frequency fields.
We report, for a rodlike nematic liquid crystal with small positive dielectric and conductivity anisotropies, and in the 90°-twisted configuration, low frequency (<2 Hz) square wave electric field generated Carr-Helfrich director modulation appearing transiently over a few seconds at each polarity reversal and vanishing almost completely under steady field conditions. Significantly, the instability is polarity sensitive, with the maximum distortion localized in the vicinity of the negative electrode, rather than in the midplane of the layer. This is revealed by the wave vector alternating in the two halves of the driving cycle between the alignment directions at the two substrates. Besides the Carr-Helfrich mechanism, quadrupolar flexoelectric polarization arising under electric field gradient is strongly indicated as being involved in the development of the transient periodic order. Similar transient instability is also observed in other nematic compounds with varying combinations of dielectric and conductivity anisotropies, showing its general nature. The study also deals with various characteristics of the electro-optic effect that emerge from the temporal variation of optical response for different driving voltages, frequencies, and temperatures.


Comparison of media for the selective culture of enteroinvasive Escherichia coli.
MacConkey, eosine-methylene blue, deoxycholate-citrate, salmonella-shigella, and xylose-lysine-deoxycholate agars were compared for their ability to support the growth and to facilitate the recovery of enteroinvasive Escherichia coli strains from artificially contaminated as well as from clinical faecal samples. When grown as pure cultures, the 78 enteroinvasive Escherichia coli strains, as a group, exhibited the same growth characteristics as did Shigella isolates ( n=59), i.e. both organisms grew more weakly than did Salmonella strains ( n=22) on the various selective plates but 4- to 10-fold better than normal Escherichia coli isolates ( n=53). Xylose-lysine-deoxycholate and deoxycholate-citrate plates were more effective in recovering enteroinvasive Escherichia coli from faecal samples than was salmonella-shigella agar. Likewise, xylose-lysine-deoxycholate agar, similar to the differentiating MacConkey and eosine-methylene blue agars, was less inhibitory for defined "sensitive" strains than were the selective media tested. Preincubating clinical faecal samples in selenite F or in gram-negative broth did not influence the recovery of enteroinvasive Escherichia coli significantly. These data show that the use of xylose-lysine-deoxycholate, in combination with MacConkey or eosine-methylene blue agar, provides the best chance for recovery of enteroinvasive Escherichia coli when randomly selecting colonies from faecal cultures for subsequent molecular or immunological identification assays.


Transcriptomic analysis reveals inflammatory and metabolic pathways that are regulated by renal perfusion pressure in the outer medulla of Dahl-S rats.
Studies exploring the development of hypertension have traditionally been unable to distinguish which of the observed changes are underlying causes from those that are a consequence of elevated blood pressure. In this study, a custom-designed servo-control system was utilized to precisely control renal perfusion pressure to the left kidney continuously during the development of hypertension in Dahl salt-sensitive rats. In this way, we maintained the left kidney at control blood pressure while the right kidney was exposed to hypertensive pressures. As each kidney was exposed to the same circulating factors, differences between them represent changes induced by pressure alone. RNA sequencing analysis identified 1,613 differently expressed genes affected by renal perfusion pressure. Three pathway analysis methods were applied, one a novel approach incorporating arterial pressure as an input variable allowing a more direct connection between the expression of genes and pressure. The statistical analysis proposed several novel pathways by which pressure affects renal physiology. We confirmed the effects of pressure on p-Jnk regulation, in which the hypertensive medullas show increased p-Jnk/Jnk ratios relative to the left (0.79 ± 0.11 vs. 0.53 ± 0.10, P < 0.01, n = 8). We also confirmed pathway predictions of mitochondrial function, in which the respiratory control ratio of hypertensive vs. control mitochondria are significantly reduced (7.9 ± 1.2 vs. 10.4 ± 1.8, P < 0.01, n = 6) and metabolomic profile, in which 14 metabolites differed significantly between hypertensive and control medullas ( P < 0.05, n = 5). These findings demonstrate that subtle differences in the transcriptome can be used to predict functional changes of the kidney as a consequence of pressure elevation.


3D imaging of biofilms on implants by detection of scattered light with a scanning laser optical tomograph.
Biofilms - communities of microorganisms attached to surfaces - are a constant threat for long-term success in modern implantology. The application of laser scanning microscopy (LSM) has increased the knowledge about microscopic properties of biofilms, whereas a 3D imaging technique for the large scale visualization of bacterial growth and migration on curved and non-transparent surfaces is not realized so far.Towards this goal, we built a scanning laser optical tomography (SLOT) setup detecting scattered laser light to image biofilm on dental implant surfaces. SLOT enables the visualization of living biofilms in 3D by detecting the wavelength-dependent absorption of non-fluorescent stains like e.g. reduced triphenyltetrazolium chloride (TTC) accumulated within metabolically active bacterial cells. Thus, the presented system allows the large scale investigation of vital biofilm structure and in vitro development on cylindrical and non-transparent objects without the need for fluorescent vital staining. We suggest SLOT to be a valuable tool for the structural and volumetric investigation of biofilm formation on implants with sizes up to several millimeters.


[Use of nanoparticles (NP) in photodynamic therapy (PDT) against cancer].
Nanotechnology is a promising interdisciplinary field for developing improved methods of diagnosis and treatment of different diseases, including cancer. Give their optical, magnetic, and structural property, the nanoparticles have been proposed to be use in the development of unconventional treatments for cancer such as photodynamic therapy (PDT). In PDT, a photosensitizing agent is used that accumulates in tumor cells, generating reactive oxygen species that causes the death of malignant cells after irradiation with light at a particular wavelength. However, the use of PDT presents different problems in its application due to the characteristics of hydrophobicity of the photosensitizers, which hinder the efficiency of administration and treatment. It is here where the use of nanoparticles is proposed as a delivery vehicle to optimize treatment application. In this review we describe the use of nanoparticles coupled to PDT in the treatment of cancer and its molecular mechanism of action.