Influence of Color-to-Gray Conversion on the Performance of Document Image Binarization: Toward a Novel Optimization Problem.
This paper presents a novel preprocessing method of color-to-gray document image conversion. In contrast to the conventional methods designed for natural images that aim to preserve the contrast between different classes in the converted gray image, the proposed conversion method reduces as much as possible the contrast (i.e., intensity variance) within the text class. It is based on learning a linear filter from a predefined data set of text and background pixels that: 1) when applied to background pixels, minimizes the output response and 2) when applied to text pixels, maximizes the output response, while minimizing the intensity variance within the text class. Our proposed method (called learning-based color-to-gray) is conceived to be used as preprocessing for document image binarization. A data set of 46 historical document images is created and used to evaluate subjectively and objectively the proposed method. The method demonstrates drastically its effectiveness and impact on the performance of state-of-the-art binarization methods. Four other Web-based image data sets are created to evaluate the scalability of the proposed method.


Early B Cell Progenitors Deficient for GON4L Fail To Differentiate Due to a Block in Mitotic Cell Division.
B cell development in Justy mutant mice is blocked due to a precursor mRNA splicing defect that depletes the protein GON4-like (GON4L) in B cell progenitors. Genetic and biochemical studies have suggested that GON4L is a transcriptional regulator that coordinates cell division with differentiation, but its role in B cell development is unknown. To understand the function of GON4L, we characterized B cell differentiation, cell cycle control, and mitotic gene expression in GON4L-deficient B cell progenitors from Justy mice. We found that these cells established key aspects of the transcription factor network that guides B cell development and proliferation and rearranged the IgH gene locus. However, despite intact IL-7 signaling, GON4L-deficient pro-B cell stage precursors failed to undergo a characteristic IL-7-dependent proliferative burst. These cells also failed to upregulate genes required for mitotic division, including those encoding the G1/S cyclin D3 and E2F transcription factors and their targets. Additionally, GON4L-deficient B cell progenitors displayed defects in DNA synthesis and passage through the G1/S transition, contained fragmented DNA, and underwent apoptosis. These phenotypes were not suppressed by transgenic expression of prosurvival factors. However, transgenic expression of cyclin D3 or other regulators of the G1/S transition restored pro-B cell development from Justy progenitor cells, suggesting that GON4L acts at the beginning of the cell cycle. Together, our findings indicate that GON4L is essential for cell cycle progression and division during the early stages of B cell development.


Towards improved animal models for evaluating social cognition and its disruption in schizophrenia: the CNTRICS initiative.
Social cognition refers to processes used to monitor and interpret social signals from others, to decipher their state of mind, emotional status and intentions, and select appropriate social behaviour. Social cognition is sophisticated in humans, being embedded with verbal language and enacted in a complex cultural environment. Its disruption characterises the entire course of schizophrenia and is correlated with poor functional outcome. Further, deficits in social cognition are related to impairment in other cognitive domains, positive symptoms (paranoia and delusions) and negative symptoms (social withdrawal and reduced motivation). In light of the significance and inadequate management of social cognition deficits, there is a need for translatable experimental procedures for their study, and identification of effective pharmacotherapy. No single paradigm captures the multi-dimensional nature of social cognition, and procedures for assessing ability to infer mental states are not well-developed for experimental therapeutic settings. Accordingly, a recent CNTRICS meeting prioritised procedures for measuring a specific construct: "acquisition and recognition of affective (emotional) states", coupled to individual recognition. Two complementary paradigms for refinement were identified: social recognition/preference in rodents, and visual tracking of social scenes in non-human primates (NHPs). Social recognition is disrupted in genetic, developmental or pharmacological disease models for schizophrenia, and performance in both procedures is improved by the neuropeptide oxytocin. The present article surveys a broad range of procedures for studying social cognition in rodents and NHPs, discusses advantages and drawbacks, and focuses on development of social recognition/preference and gaze-following paradigms for improved study of social cognition deficits in schizophrenia and their potential treatment.


Quantitative investigation of bone microvascularization from 3D synchrotron micro-computed tomography in a rat model.
A new method for simultaneous 3D imaging and analysis of microvascularization and bone microstructure in rat bone is developed. The method is based on the use of quantitative synchrotron micro-computed tomography (SR-microCT) coupled to an automatic image analysis procedure. Analysis of bone microvascularization is generally performed from 2D histology. The proposed method enables for the first time the simultaneous 3D analysis of microvascularization and bone microstructure in a rat model. It was applied to investigate the effect of intermittent parathyroid hormone (PTH) administration on angiogenesis and osteogenesis in rats. Rats were posthumously injected with a contrast agent and subsequently imaged. The algorithm allowed the reconstruction and the extraction of 3D quantitative parameters both on bone microstructure and microvascularization. Due to the short acquisition times of SR-microCT and the efficiency of the image analysis algorithm, a large data set was analyzed, which permitted statistical analysis of the measured parameters. Statistical analysis confirmed that treatment with PTH significantly increased bone volume and thickness, but decreased bone mineralization. It was further revealed that treatment with PTH significantly increased average vessel thickness.


Tissue electroporation. Observation of reversible electrical breakdown in viable frog skin.
Experiments by others have used isolated cell or bilayer membrane preparations to study the dramatic phenomena associated with electroporation. The present study observes electroporation behavior in an intact tissue. Viable samples of frog skin (Rana pipiens) were exposed to short electrical pulses of varying width and magnitude under "charge injection" conditions. After a pulse, the transtissue potential decayed with two distinct time constants, one short (tau approximately 0.3 ms) and the other longer (tau L approximately 2 ms). Above thresholds for the pulse magnitude and for the pulse width tau L decreased significantly, with progressively smaller tau L as the pulse magnitude and width increased. The postpulse potential, delta Utissue (t), and resistance, Rtissue, also decreased progressively. The tissue subsequently recovered to its original resistance and open circuit potential, delta U tissue,oc, within 2-3 min after a pulse. At that time another pulse experiment could be carried out, demonstrating repeatability and reversibility. No significant permanent changes in Rtissue and delta Utissue,oc were found. This is interpreted as avoidance of significant tissue damage. Taken together, these dramatic phenomena are characteristic of the reversible electrical breakdown previously observed in charge injection experiments with artificial planar bilayer membranes and with isolated cell membranes by similar very short pulses. The present experiments therefore demonstrate that electroporation can be repeatedly caused and observed in a viable tissue without apparent damage.


Pathogenesis-related acidic beta-1,3-glucanase genes of tobacco are regulated by both stress and developmental signals.
Three pathogenesis-related (PR) proteins of tobacco are acidic isoforms of beta-1,3-glucanase (PR-2a, -2b, -2c). We have cloned and sequenced a partial cDNA clone (lambda FJ1) corresponding to one of the PR-2 beta-1,3-glucanases. A small gene family encodes the PR-2 proteins in tobacco, and similar genes are present in a number of plant species. We analyzed the stress and developmental regulation of the tobacco PR-2 beta-1,3-glucanases by using northern and western analyses and a new technique to assay enzymatic activity. Stress caused by both thiamine and tobacco mosaic virus (TMV) infection resulted in a dramatic increase in the levels of PR-2 mRNA, protein, and enzyme activities. The increased PR-2 gene expression in upper uninoculated leaves of plants infected with TMV also suggests a role in systemic acquired resistance. During floral development, a number of beta-1,3-glucanase activities were observed in all flower tissues. However, PR-2 polypeptides were observed only in sepal tissue. In contrast, an mRNA that hybridized to the PR-2 cDNA was present in stigma/style tissue and the sepals. Primer extension analysis confirmed the identity of the PR-2 mRNA in sepals, but indicated that the beta-1,3-glucanase gene expressed in the stigma/style of flowers was distinct from the PR-2 genes. The induction of PR-2 protein synthesis by both stress and developmental signals was accompanied by a corresponding increase in the steady-state levels of PR-2 mRNA, suggesting that PR-2 gene expression is regulated, in part, at the level of mRNA accumulation.


Distinction between antinuclear antibody and P-ANCA.
To differentiate between perinuclear immunofluorescence staining of antinuclear antibody (ANA) and the perinuclear form of anti-neutrophil cytoplasmic antibody (P-ANCA), the pattern after formaldehyde vapour fixation of normal human neutrophils was compared with that of standard ethanol fixation. Fifteen out of 17 myeloperoxidase antibody positive sera showed cytoplasmic staining on formaldehyde vapour fixed cells; 30 of the 32 ANA positive samples became negative or gave weak nuclear staining on the same substrate. Formaldehyde vapour fixation is a simple, useful technique for differentiating between ANA and P-ANCA.


Figure-ground interaction in the human visual cortex.
Discontinuities in feature maps serve as important cues for the location of object boundaries. Here we used multi-input nonlinear analysis methods and EEG source imaging to assess the role of several different boundary cues in visual scene segmentation. Synthetic figure/ground displays portraying a circular figure region were defined solely by differences in the temporal frequency of the figure and background regions in the limiting case and by the addition of orientation or relative alignment cues in other cases. The use of distinct temporal frequencies made it possible to separately record responses arising from each region and to characterize the nature of nonlinear interactions between the two regions as measured in a set of retinotopically and functionally defined cortical areas. Figure/background interactions were prominent in retinotopic areas, and in an extra-striate region lying dorsal and anterior to area MT+. Figure/background interaction was greatly diminished by the elimination of orientation cues, the introduction of small gaps between the two regions, or by the presence of a constant second-order border between regions. Nonlinear figure/background interactions therefore carry spatially precise, time-locked information about the continuity/discontinuity of oriented texture fields. This information is widely distributed throughout occipital areas, including areas that do not display strong retinotopy.


Self-concept among youth with a chronic illness: a meta-analytic review.
The aim of this study was to use meta-analytic techniques to compare self-concept between children and adolescents (abbreviated to youth) with a chronic illness versus healthy controls, and to examine methodological influences on effect sizes. Databases were searched for asthma, cerebral palsy, diabetes, epilepsy, and juvenile arthritis. Inclusion criteria were: 1) original research studies in English; 2) youth <18 years; 3) the inclusion of self-reported self-concept; and 4) data available to estimate effect sizes. Study quality was assessed with a modified Quality Index. Effect sizes were calculated as Hedges' g using a random effects model. A total of 60 studies were analyzed. On average, youth with a chronic illness had compromised self-concept, d = -0.17 [-0.27, -0.07]. However, type of control group exerted a moderating influence that resulted in discrepant findings. Studies based on normative data reported higher self-concept in youth with a chronic illness, d = 0.27 [0.06, 0.47], whereas studies that recruited healthy controls reported lower self-concept in youth with a chronic illness, d = -0.25 [-0.34, -0.15]. Self-concept is compromised in youth with a chronic illness; however, the effect size may be underestimated because of methodological weaknesses and systematic biases in existing studies. Future research should avoid the use of normative data and employ rigorous methods to ensure representative sampling and control of confounding variables to better appreciate the impact of chronic illness on youths' self-concept.


Cancellous bone and theropod dinosaur locomotion. Part III-Inferring posture and locomotor biomechanics in extinct theropods, and its evolution on the line to birds.
This paper is the last of a three-part series that investigates the architecture of cancellous bone in the main hindlimb bones of theropod dinosaurs, and uses cancellous bone architectural patterns to infer locomotor biomechanics in extinct non-avian species. Cancellous bone is highly sensitive to its prevailing mechanical environment, and may therefore help further understanding of locomotor biomechanics in extinct tetrapod vertebrates such as dinosaurs. Here in Part III, the biomechanical modelling approach derived previously was applied to two species of extinct, non-avian theropods, Daspletosaurus torosus and Troodon formosus. Observed cancellous bone architectural patterns were linked with quasi-static, three-dimensional musculoskeletal and finite element models of the hindlimb of both species, and used to derive characteristic postures that best aligned continuum-level principal stresses with cancellous bone fabric. The posture identified for Daspletosaurus was largely upright, with a subvertical femoral orientation, whilst that identified for Troodon was more crouched, but not to the degree observed in extant birds. In addition to providing new insight on posture and limb articulation, this study also tested previous hypotheses of limb bone loading mechanics and muscular control strategies in non-avian theropods, and how these aspects evolved on the line to birds. The results support the hypothesis that an upright femoral posture is correlated with bending-dominant bone loading and abduction-based muscular support of the hip, whereas a crouched femoral posture is correlated with torsion-dominant bone loading and long-axis rotation-based muscular support. Moreover, the results of this study also support the inference that hindlimb posture, bone loading mechanics and muscular support strategies evolved in a gradual fashion along the line to extant birds.


The pattern of inflammatory/anti-inflammatory cytokines and chemokines in type 1 diabetic patients over time.
To evaluate the profile of pro- and anti-inflammatory cytokines in type 1 diabetes mellitus (T1DM) and the way they are connected in co-regulated networks and determine whether disease duration influences their pattern. Plasma levels of 20 cytokines and soluble CD40 (sCD40) from 44 uncomplicated patients and 22 healthy controls (HCs) were measured using enzyme-linked immunosorbent assay (ELISA) and protein array technology. Patients showed significantly higher levels of sCD40, IL-1a, IL-2, IL-4, IL-5, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein (MIP)-1a, MIP-1b, regulated on activation normal T cell expressed and secreted (RANTES), matrix metalloproteinase (MMP)-9, and a trend to higher IL-6 than did HCs. RANTES and sCD40 discriminated significantly between diabetics and HCs. In patients with disease duration >6 months, cytokines were organized in two clusters mainly regulated by Th17 and Th1/Th2 cells respectively, while in those with disease duration <or=6 months a set of Th1-cytokines was separated apart from the second cluster. Monocyte chemotactic protein (MCP)-1 was revealed as the most discriminant factor between patients with disease duration of more than and less than 6 months. A parallel elevation of both inflammatory and anti-inflammatory cytokines was observed in patients compared with HCs. In T1DM patients with disease duration <or=6 months, Th1-cytokines were organized on a separate cluster, suggesting a possible role of Th1 cells in the progress of beta-cell destruction during the first period of the disease.


Anterior femoroacetabular impingement: part I. Techniques of joint preserving surgery.
The exact pathomechanism responsible for osteoarthritis (OA) of the nondysplastic hip has remained unknown for many years. There is, however, emerging clinical evidence implicating femoroacetabular impingement as an etiologic factor for having early OA of the hip develop. Femoroacetabular impingement is an abutment conflict occurring between the proximal femur and the acetabular rim arising from morphologic abnormalities affecting the acetabulum or the proximal femur, or both. The repetitive mechanical conflict occurring during motion, particularly flexion and internal rotation, can lead to lesions of acetabular labrum and, even more serious, the adjacent acetabular cartilage. Surgical treatment of femoroacetabular impingement focuses on improving the clearance for hip motion and alleviation of femoral abutment against the acetabular rim. We will describe the rationale for the treatment of this condition, and discuss the technique of joint-preserving surgery.


Cross-cultural comparison of the patient-centeredness of the hidden curriculum between a Saudi Arabian and 9 US medical schools.
The implicit "hidden curriculum" strongly influences medical students' perceptions of the importance of patient-centeredness. A new instrument, the Communication, Curriculum, and Culture Survey (C3), already used to assess this hard-to- access part of the curriculum in the US, has potential for use in cross-cultural comparisons. To use the C3 to perform a pilot cross-cultural comparison of the patient-centeredness of the hidden curriculum between a Saudi medical school and 9 U.S. medical schools. Senior Saudi medical students completed the C3 and a second instrument, the Patient-Provider Orientation Scale (PPOS), which measured their attitudes toward patient-centered behavior. Senior Saudi medical students. 139/256 (54%) Saudis completed the C3; 122/256(48%) completed the PPOS. Means for 2 out of 3 of the C3's domains (0-100 scale) were lower for the Saudis than those for the Americans (95% confidence intervals in parentheses): 47 (45, 50) vs. 55 (53, 58); 54 (50, 58) vs. 68 (67, 70); they overlapped in the third: 60 (57, 63) vs. 62 (60, 63). The mean Saudi PPOS score was 4.0 (3.9, 4.1); for the American medical schools, 4.8 (4.8-4.8) (1-6, least to most patient-centered). In this preliminary study the data suggest that the patient-centeredness of the hidden curriculum differs in Saudi and US medical schools in 2 out of 3 domains. Cross-cultural use of instruments such as the C3 can highlight such important differences and help educators evaluate their curriculum from an international, as well as a local perspective. Use of instruments across borders is a growing trend and an indicator of the increasing globalization of medical education.


Investigation of the Affinity of Ceftobiprole for Selected Cyclodextrins Using Molecular Dynamics Simulations and HPLC.
This paper presents the theoretical calculations of the inclusion complex formation between native ceftobiprole, a promising antibiotic from the cephalosporin group, and selected cyclodextrins (CDs) approved by the European Medicines Agency. Ceftobiprole was studied in three protonation states predicted from pKa calculations, along with three selected CDs in a stoichiometric ratio of 1:1. It was introduced into the CD cavity in two opposite directions, resulting in 18 possible combinations. Docking studies determined the initial structures of the complexes, which then served as starting structures for molecular dynamics simulations. The analysis of the obtained trajectories included the spatial arrangement of ceftobiprole and CD, the hydrogen bonds forming between them, and the Gibbs free energy (ΔG) of the complex formation, which was calculated using the Generalised Born Surface Area (GBSA) equation. Among them, a complex of sulfobutyl ether- (SBE-) β-CD with protonated ceftobiprole turned out to be the most stable (ΔG = -12.62 kcal/mol = -52.80 kJ/mol). Then, experimental studies showed changes in the physiochemical properties of the ceftobiprole in the presence of the CDs, thus confirming the validity of the theoretical results. High-performance liquid chromatography analysis showed that the addition of 10 mM SBE-β-CD to a 1 mg/mL solution of ceftobiprole in 0.1 M of HCl increased the solubility 1.5-fold and decreased the degradation rate constant 2.5-fold.


Pulmonary langerhans cell histiocytosis case with diabetes insipidus and tuberculosis.
A 19-year-old male patient was observed due to having central diabetes insipidus (DI) for five years. He had a history of smoking 5-10 cigarettes a day for two years, but stopped smoking from the last month. The computerized tomography revealed thin-walled cystic lesions in different sizes more dominantly in the upper lobes and consolidated areas in the left upper and lower lobes. The wedge resection from the right lower lobe revealed pulmonary langerhans cell histiocytosis. Follow-up acid-fast bacteria (AFB) examinations revealed (+++) and antituberculous treatment was started. On the 40th day of the anti-tuberculosis treatment, the patient applied once again due to fever and chest pain. Although infiltrations persisted in the left upper and middle zones in the postero-anterior lung rontgenogram, right-sided pneumothorax was detected. The case is considered tuberculosis and the patient continued to receive anti-TB treatment under the close supervision.


Acute Effect of Different Velocity-Based Training Protocols on 2000-meter Rowing Ergometer Performance.
Leandro Quidel-Catrilelbún, ME, Ruiz-Alias, SA, García-Pinillos, F, Ramirez-Campillo, R, and Pérez-Castilla, A. Acute effect of different velocity-based training protocols on 2000-m rowing ergometer performance. J Strength Cond Res 38(1): e8-e15, 2024-This study aimed to explore the acute effect of 4 velocity-based resistance training (VBT) protocols on 2000-m rowing ergometer (RE2000) time trial, as well as the behavior of the maximal neuromuscular capacities when RE2000 is performed alone or preceded by VBT protocols in the same session. Fifteen male competitive rowers (15-22 years) undertook 5 randomized protocols in separate occasions: (a) RE2000 alone (control condition); (b) VBT against 60% of 1 repetition maximum (1RM) with a velocity loss in the set of 10% followed by RE2000 (VBT60-10 + RE2000); (c) VBT against 60% 1RM with a velocity loss in the set of 30% followed by RE2000 (VBT60-30 + RE2000); (d) VBT against 80% 1RM with a velocity loss in the set of 10% followed by RE2000 (VBT80-10 + RE2000); (e) VBT against 80% 1RM with a velocity loss in the set of 30% followed by RE2000 (VBT80-30 + RE2000). The load-velocity relationship (load-axis intercept [L0], velocity-axis intercept [v0], and area under the load-velocity relationship line [Aline]) was used to evaluate the maximal neuromuscular capacities during the prone bench pull exercise before and after each protocol. The time trial was significantly longer for VBT60-30 + RE2000 and VBT80-30 + RE2000 than for RE2000, VBT60-10 + RE2000 and VBT80-10 + RE2000 (all p < 0.001; ES = 0.10-0.15). L0 and Aline were significantly reduced after all protocols (p < 0.001; ES = 0.10-0.13), with Aline reduction more accentuated for VBT60-10 + RE2000, VBT60-30 + RE2000, VBT80-30 + RE2000, and RE2000 (all p = 0.001; ES = 0.11-0.18) than for VBT80-10 + RE2000 (p = 0.065; ES = 0.05). Therefore, VBT protocols with greater velocity loss in the set (30% vs. 10%) negatively affected subsequent rowing ergometer performance, in line with impairment in Aline pulling performance.


Clinical findings, imaging characteristics and outcome in catastrophic post-encephalitic epilepsy.
The aim of this study is to characterize the clinical features and prognostic factors for intractable, post-encephalitic epilepsy. We studied retrospectively 42 patients (26 men) evaluated between 1982 and 1999. MRI, neuropsychological findings, interictal and ictal scalp EEG were reviewed for all patients. Fifteen patients had additional stereo EEG (SEEG) studies. The mean age at encephalitis was 17 years (SD = 15.5); etiology was identified in 18 patients. During the acute illness, 79% had status epilepticus (SE) or recurrent seizures and 76% were in coma; mean Glasgow outcome scale (GOS) was 3.6 (SD = 0.8). The mean latency to seizure onset was 0.8 years (SD = 1.9). The majority (72%) presented with complex partial seizures with or without secondary generalization. According to interictal epileptiform findings and the predominant seizure onset pattern as found on scalp EEG, patients were unilateral temporal (UTLE) = 8, bilateral temporal (BTLE) = 12, and extratemporal/multifocal or generalized (ETMFE) = 22 patients. MRI atrophy and/or signal changes were unilateral temporal in 7 (18%), bilateral temporal in 5 (13%), multilobar/diffuse in 20 (51%), and absent in 7 (18%). ANOVA revealed significant differences in mean GOS between UTLE versus BTLE and ETMFE (4.7 versus 3.2 versus 3.6; p < 0.0001), but not in age at encephalitis. Latency to the first unprovoked seizure was shorter in patients with ETMFE compared to UTLE and BTLE (p < 0.01). Surgery was performed in 24 patients. The best outcome was obtained in UTLE (7/8 class I and II). In the others, outcome was poor in the majority (13/16 class III and IV). There is a small subgroup of patients with postencephalitic UTLE for whom the outcome is favorable. The majority of our patients had multifocal seizure onset with BTLE and ETMFE, and poor outcome after surgical treatment.


Energy-sensitive cryogenic detectors for high-mass biomolecule mass spectrometry.
Energy-sensitive calorimetric detectors that operate at low temperatures ("cryogenic detectors") have recently been applied for the first time as ion detectors in time-of-flight mass spectrometry. Compared to conventional, ionization-based detectors, which rely on secondary electron formation or the charge created in a semiconductor, cryogenic detectors measure low-energy solid state excitations created by a particle impact. This energy sensitivity of cryogenic detectors results in several potential advantages for TOF-MS. Cryogenic detectors are expected to have near 100% efficiency even for very large, slow-moving molecules, in contrast to microchannel plates whose efficiency drops considerably at large mass. Thus, cryogenic detectors could contribute to extending the mass range accessible by TOF-MS and help improving detection limits. In addition, the energy resolution provided by cryogenic detectors can be used for charge discrimination and studies of ion fragmentation, ion-detector interaction, and internal energies of large molecular ions. Cryogenic detectors could therefore prove to be a valuable diagnostic tool in TOF-MS. Here, we give a general introduction to the cryogenic detector types most applicable to TOF-MS including those types already used in several TOF-MS experiments. We review and compare the results of these experiments, discuss practical aspects of operating cryogenic detectors in TOF-MS systems, and describe potential near future improvements of cryogenic detectors for applications in mass spectrometry.


Induction of type I and type III interferons by Borrelia burgdorferi correlates with pathogenesis and requires linear plasmid 36.
The capacity for Borrelia burgdorferi to cause disseminated infection in humans or mice is associated with the genotype of the infecting strain. The cytokine profiles elicited by B. burgdorferi clinical isolates of different genotype (ribosomal spacer type) groups were assessed in a human PBMC co-incubation model. RST1 isolates, which are more frequently associated with disseminated Lyme disease in humans and mice, induced significantly higher levels of IFN-α and IFN-λ1/IL29 relative to RST3 isolates, which are less frequently associated with disseminated infection. No differences in the protein concentrations of IFN-γ, IL-1β, IL-6, IL-8, IL-10 or TNF-α were observed between isolates of differing genotype. The ability of B. burgdorferi to induce type I and type III IFNs was completely dependent on the presence of linear plasmid (lp) 36. An lp36-deficient B. burgdorferi mutant adhered to, and was internalized by, PBMCs and specific dendritic cell (DC) subsets less efficiently than its isogenic B31 parent strain. The association defect with mDC1s and pDCs could be restored by complementation of the mutant with the complete lp36. The RST1 clinical isolates studied were found to contain a 2.5-kB region, located in the distal one-third of lp36, which was not present in any of the RST3 isolates tested. This divergent region of lp36 may encode one or more factors required for optimal spirochetal recognition and the production of type I and type III IFNs by human DCs, thus suggesting a potential role for DCs in the pathogenesis of B. burgdorferi infection.


Transferrin saturation with intravenous irons: an in vitro study.
Iron deficiency anemia in chronic kidney disease is commonly treated with one of three intravenous irons-iron dextran, iron sucrose, or iron gluconate. Substantial pharmacologic differences between drugs exist, but their ability to saturate transferrin has not been compared. Drugs that may lead to rapid transferrin saturation may lead to greater efficacy but also increased toxicity if transferring-mediated uptake of iron is the basis of this toxicity. We studied the in vitro ability of the three intravenous irons to donate iron to transferrin. Transferrin saturation was studied by direct visualization of the transferrin bands by urea polyacrylamide gel electrophoresis (PAGE), as well as a functional assay that evaluated the ability of iron to half saturate transferrin in a dose-dependent (0 to 100 microg/mL) and time-dependent (15 to 180 min) manner. Half-maximal dose (EC(50)) of iron needed to saturate transferrin was evaluated. Nondextran irons were able to saturate transferrin in a dose-dependent and time-dependent manner. There was more rapid transferrin saturation with iron gluconate compared to iron sucrose. The slope of the EC(50) versus dose iron gluconate titration curve was -0.021 nmol/microg/mL (95% CI -0.025 to -0.017, P < 0.0001), for iron sucrose -0.006 nmol/microg/mL (95% CI -0.010 to -0.002, P= 0.002), and for iron dextran -0.001 nmol/microg/mL (95% CI -0.004 to 0.003, P > 0.2). The least square mean EC(50) computed for mean iron concentration was 5.95 nmol for iron gluconate (95% CI 5.82 to 6.08), 6.73 nmol for iron sucrose (95% CI 6.59 to 6.86), and 7.24 nmol for iron dextran (95% CI 7.11 to 7.38). Similar results were seen for the time-dependent transferrin saturation (drug x time interaction, F 6.0, P < 0.01). Urea PAGE analysis showed similar results as the functional assay. Substantial heterogeneity in direct iron transfer from iron pharmaceuticals in vitro suggests that differences may exist in safety and efficacy of these drugs in vivo. In vivo studies are needed to compare the safety and efficacy of existing nondextran parenteral irons to better define the therapeutic ratio.


Nucleolar Proteome Analysis and Proteasomal Activity Assays Reveal a Link between Nucleolus and 26S Proteasome in A. thaliana.
In all eukaryotic cells, the nucleolus is functionally and structurally linked to rRNA synthesis and ribosome biogenesis. This compartment contains as well factors involved in other cellular activities, but the functional interconnection between non-ribosomal activities and the nucleolus (structure and function) still remains an open question. Here, we report a novel mass spectrometry analysis of isolated nucleoli from Arabidopsis thaliana plants using the FANoS (Fluorescence Assisted Nucleolus Sorting) strategy. We identified many ribosome biogenesis factors (RBF) and proteins non-related with ribosome biogenesis, in agreement with the recognized multi-functionality of the nucleolus. Interestingly, we found that 26S proteasome subunits localize in the nucleolus and demonstrated that proteasome activity and nucleolus organization are intimately linked to each other. Proteasome subunits form discrete foci in the disorganized nucleolus of nuc1.2 plants. Nuc1.2 protein extracts display reduced proteasome activity in vitro compared to WT protein extracts. Remarkably, proteasome activity in nuc1.2 is similar to proteasome activity in WT plants treated with proteasome inhibitors (MG132 or ALLN). Finally, we show that MG132 treatment induces disruption of nucleolar structures in WT but not in nuc1.2 plants. Altogether, our data suggest a functional interconnection between nucleolus structure and proteasome activity.


Oral berotralstat for the prophylaxis of hereditary angioedema attacks in patients in Japan: A phase 3 randomized trial.
With no approved treatments in Japan for the prevention of hereditary angioedema (HAE) attacks, there is a significant unmet need for long-term prophylactic therapies for Japanese patients with HAE. Berotralstat (BCX7353) is an oral, once-daily, highly selective inhibitor of plasma kallikrein in development for prophylaxis of angioedema attacks in HAE patients. APeX-J is a phase 3, randomized, double-blind, placebo-controlled, parallel-group, 3-part trial conducted in Japan (University Hospital Medical Information Network identifier, UMIN000034869; ClinicalTrials.gov identifier, NCT03873116). Patients with a clinical diagnosis of type 1 or 2 HAE underwent a prospective run-in period of 56 days to determine eligibility, allowing enrollment of those with ≥2 expert-confirmed angioedema attacks. Patients were randomly assigned (1:1:1) and stratified by baseline attack rate (≥2 vs. <2 expert-confirmed attacks/month between screening and randomization) to receive once-daily berotralstat 110 mg, berotralstat 150 mg, or placebo. The primary endpoint was the rate of expert-confirmed angioedema attacks during dosing in the 24-week treatment period. Nineteen patients were randomized to receive once-daily berotralstat 110 mg (n = 6), berotralstat 150 mg (n = 7), or placebo (n = 6). Treatment with berotralstat 150 mg significantly reduced HAE attacks relative to placebo (1.11 vs. 2.18 attacks/month, p = .003). The most frequently reported treatment-emergent adverse events (TEAEs) in berotralstat-treated patients (n = 13) were nasopharyngitis (n = 4, 31%), abdominal pain, cough, diarrhea, and pyrexia (n = 2 each, 15%). Orally administered, once-daily berotralstat 150 mg significantly reduced the frequency of HAE attacks and was safe and well tolerated, supporting its use as a prophylactic therapy in patients with type 1 or 2 HAE in Japan.


Peripheral Blood Biomarkers Associated With Improved Functional Outcome in Patients With Chronic Left Ventricular Dysfunction: A Biorepository Evaluation of the FOCUS-CCTRN Trial.
Cell therapy trials for heart failure (HF) have shown modest improvement; however, the mechanisms underlying improvement in some patients but not others are not well understood. Although immune cells are important in the course of HF, our understanding of the immune processes in HF is limited. The objective of this study was to evaluate associations between temporal changes in peripheral blood (PB) cell subpopulations and improved outcome in patients with chronic ischemic cardiomyopathy after bone marrow-derived mononuclear cell therapy or placebo in the FOCUS-CCTRN trial. Peripheral blood was collected at days 0, 1, 30, 90, and 180 from consented participants. We used flow cytometry to compare PB populations in patients with the best (cohort 1) or worst functional outcome (cohort 2) in three primary endpoints: left ventricular (LV) ejection fraction, LV end-systolic volume, and maximal oxygen consumption (VO2 max). A linear mixed model was used to assess changes over time in 32 cell populations. The difference between each time point and baseline was calculated as linear contrast. Compared with cohort 2, patients who improved (cohort 1) had a higher frequency of CD45+CD19+ B cells at days 0, 1, 90, and 180. CD11B+ cells increased over baseline at day 1 in both cohorts and remained higher in cohort 2 until day 30. CD45+CD133+ progenitor cells decreased over baseline at day 30 in cohort 1. We identified specific cell subpopulations associated with improved cardiac function in patients with chronic LV dysfunction. These findings may improve patient selection and prediction of outcomes in cell therapy trials.


TuLUMIS - a tunable LED-based underwater multispectral imaging system.
Multispectral imaging (MSI) is widely used in terrestrial applications to help increase the discriminability between objects of interest. While MSI has shown potential for underwater geological and biological surveys, it is thus far rarely applied underwater. This is primarily due to the fact light propagation in water is subject to wavelength dependent attenuation and tough working conditions in the deep ocean. In this paper, a novel underwater MSI system based on a tunable light source is presented which employs a monochrome still image camera with flashing, pressure neutral color LEDs. Laboratory experiments and field tests were performed. Results from the lab experiments show an improvement of 76.66% on discriminating colors on a checkerboard by using the proposed imaging system over the use of an RGB camera. The field tests provided in situ MSI observations of pelagic fauna, and showed the first evidence that the system is capable of acquiring useful imagery under real marine conditions.


Asymptomatic presence of Nosema spp. in Spanish commercial apiaries.
Nosemosis is caused by intracellular parasites (Nosema apis and Nosema ceranae) that infect the midgut epithelial cells in adult honey bees. Recent studies relate N. ceranae to Colony Collapse Disorder and there is some suggestion that Nosema spp., especially N. ceranae, induces high mortality in honey bees, a fact that is considered as a serious threat for colony survival. 604 samples of adult honey bees for Nosema spp. analysis were collected from beekeeping colonies across Spain and were analysed using PCR with capillary electrophoresis. We also monitored 77 Andalusian apiaries for 2 years; the sampled hives were standard healthy colonies, without any special disease symptoms. We found 100% presence of Nosema spp. in some locations, indicating that this parasite was widespread throughout the country. The two year monitoring indicated that 87% of the hives with Nosema spp. remained viable, with normal honey production and biological development during this period of time. The results of these trials indicated that both N. ceranae and N. apis could be present in these beehives without causing disease symptom and that there is no evidence for the replacement of N. apis by N. ceranae, supporting the hypothesis that nosemosis is not the main reason of the collapse and death of beehives.


Characterisation of Endogenous Peptides Present in Virgin Olive Oil.
The low molecular weight peptide composition of virgin olive oil (VOO) is mostly unknown. We aimed to investigate the composition of the endogenous peptides present in VOO, the protein sources from which those peptides originate and their biological activities. A water-soluble extract containing peptides was obtained from VOO. The peptides were separated by size-exclusion using fast protein liquid chromatography, and the low molecular weight fraction (1600-700 kDa) was analysed by nanoscale liquid chromatography Orbitrap coupled with tandem mass spectrometry and de novo sequencing. Nineteen new peptides were identified by Peaks database algorithm, using the available Olea europaea (cv. Farga) genome database. Eight new peptides were also identified by Peaks de novo sequencing. The protein sources of the peptides detected in the database by Peaks DB were identified by BLAST-P search. Seed storage proteins were among the most frequent sources of VOO peptides. BIOPEP software was used to predict the biological activities of peptides and to simulate (in silico) the proteolytic activity of digestive enzymes on the detected peptide sequences. A selection of synthetic peptides was obtained for investigation of their bioactivities. Peptides VCGEAFGKA, NALLCSNS, CPANGFY, CCYSVY and DCHYFL possessed strong ACE-inhibitory and antioxidant activities in vitro. Antioxidant peptides could play a role in VOO quality.


An observational study of workflows to support fecal testing for colorectal cancer screening in primary care practices serving Medicaid enrollees.
Screening supports early detection and treatment of colorectal cancer (CRC). Provision of fecal immunochemical tests/fecal occult blood tests (FIT/FOBT) in primary care can increase CRC screening, particularly in populations experiencing health disparities. This study was conducted to describe clinical workflows for FIT/FOBT in Oregon primary care practices and to identify specific workflow processes that might be associated (alone or in combination) with higher (versus lower) CRC screening rates. Primary care practices were rank ordered by CRC screening rates in Oregon Medicaid enrollees who turned age 50 years from January 2013 to June 2014 (i.e., newly age-eligible). Practices were recruited via purposive sampling based on organizational characteristics and CRC screening rates. Data collected were from surveys, observation visits, and informal interviews, and used to create practice-level CRC screening workflow reports. Data were analyzed using descriptive statistics, qualitative data analysis using an immersion-crystallization process, and a matrix analysis approach. All participating primary care practices (N=9) used visit-based workflows, and four higher performing and two lower performing used population outreach workflows to deliver FIT/FOBTs. However, higher performing practices (n=5) had more established workflows and staff to support activities. Visit-based strategies in higher performing practices included having dedicated staff identify patients due for CRC screening and training medical assistants to review FIT/FOBT instructions with patients. Population outreach strategies included having clinic staff generate lists and check them for accuracy prior to direct mailing of kits to patients. For both workflow types, higher performing clinics routinely utilized systems for patient reminders and follow-up after FIT/FOBT distribution. Primary care practices with higher CRC screening rates among newly age-eligible Medicaid enrollees had more established visit-based and population outreach workflows to support identifying patients due for screening, FIT/FOBT distribution, reminders, and follow up. Key to practices with higher CRC screening was having medical assistants discuss and review FIT/FOBT screening and instructions with patients. Findings present important workflow processes for primary care practices and may facilitate the implementation of evidence-based interventions into real-world, clinical settings.


[Differences in health status--policy, life style and genes].
The five Nordic countries seem rather homogeneous when assessed from abroad. They do have a lot in common: similar political systems, same standard of living, and even a common language root for a large part of the population. The Nordic countries have collaborated quite closely after the Second World War in fields like the labour market, pension rights and passport control. However, the health status has varied considerably during the twentieth century, even though death rates from some of the most common diseases such as cardiovascular disease are starting to converge. Vital statistics have been compared with regard to some common diseases. The differences are described according to current knowledge on preventive programmes such as breast cancer screening and screening for cardiovascular risk. The prevalence of some lifestyle variables such as alcohol, smoking, physical activity and fat consumption are reported. Lung cancer and cancer of the stomach still show substantial variation between the countries. Both discrepancies and similarities must be related to lifestyle, culture, politics and to some extent genetics. The five countries have their own viewpoints on tobacco, alcohol and nutrition policy, with the Danes the more liberal, and Swedes, Finns and Norwegians pursuing a stricter policy. These differences are to some extent reflected in the incidence of lung cancer, which are more positive in Finland, and the high death rates from liver cirrhosis in Denmark. The relatively unsatisfactory development in Denmark may be a consequence of a much longer period of structural unemployment than the other countries, as well as a more liberal attitude towards alcohol and smoking.


[Application and safety of hydroxychloroquine in chronic disease among children].
Objective: To analyze the disease spectrum among children who were using hydroxychloroquine (HCQ), and evaluate the drug's safety and compliance. Methods: From January 2008 to December 2019, children from Children's Hospital of Fudan University who used HCQ were selected as subjects, the disease spectrum of HCQ was analyzed, and the drug safety and compliance were evaluated for the patients who were followed up for more than 6 months. Demographic information, diagnosis, initial dose, time of continuous use, cumulative dosage and related adverse reactions report, project and the results of eye test were collected. Results: A total of 528 cases used HCQ during the 12 years, with 156 male cases and 372 female cases, and age at initial medication was (10.5±3.2) years. Among them, 514 cases (97.3%) had rheumatic disease, 5 had pulmonary interstitial lesions and 9 had other system diseases. The top three of the rheumatic diseases were systemic lupus erythematosus (SLE) in 316 cases (316/514,61.5%), juvenile idiopathic arthritis in 69 cases (69/514,13.4%), and juvenile dermatomyositis in 56 cases (56/514,10.9%). During the same period, 397 cases were diagnosed with SLE, and the utilization rate was 79.6% (316/397), which was the highest compared with other diseases and increased year by year. Pulmonary interstitial lesions included 4 cases with SFTPC gene defect related interstitial lung disease. Of the 528 ceses who were treated with HCQ, 397 cases were included for evaluating HCQ's safety and compliance, the initial dose was (4.2±1.0) mg/kg, duration was 29.6 (14.9, 48.8) months, the longest usage time was 127 months, the largest cumulative dosage was 566.8 g. The continuous usage duration (Z=-3.191, P=0.001) of SLE was significantly higher than those of other diseases, as well as cumulative dosage (Z=-5.355, P=0.001). All cases received comprehensive eye exams before medication, 354 cases (354/397, 89.2%) were followed up in the ophthalmological department, and 65.5% (232/354) of them could be reviewed regularly at least 1 time per year. One case suffered from severe skin adverse reactions when the drug was used for 32.7 months, and no other serious adverse reactions were reported. HCQ related retinopathy was not seen during the follow-up period. There were 5 cases stopped HCQ on their own. Conclusions: HCQ was widely used in rheumatic disease in children, especially in those with SLE. It was safe for long-time usage in children, and the medication compliance and the ophthalmic follow-up was good.


The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex.
Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (TMS). When applied to motor cortex it leads to after-effects on corticospinal and corticocortical excitability that may reflect LTP/LTD-like synaptic effects. An inhibitory form of TBS (continuous, cTBS) suppresses MEPs, and spinal epidural recordings show this is due to suppression of the I1 volley evoked by TMS. Here we investigate whether the excitatory form of TBS (intermittent, iTBS) affects the same I-wave circuitry. We recorded corticospinal volleys evoked by single pulse TMS of the motor cortex before and after iTBS in three conscious patients who had an electrode implanted in the cervical epidural space for the control of pain. As in healthy subjects, iTBS increased MEPs, and this was accompanied by a significant increase in the amplitude of later I-waves, but not the I1 wave. In two of the patients we tested the excitability of the contralateral cortex and found a significant suppression of the late I-waves. The extent of the changes varied between the three patients, as did their age. To investigate whether age might be a significant contributor to the variability we examined the effect of iTBS on MEPs in 18 healthy subjects. iTBS facilitated MEPs evoked by TMS of the conditioned hemisphere and suppressed MEPs evoked by stimulation of the contralateral hemisphere. There was a slight but non-significant decline in MEP facilitation with age, suggesting that interindividual variability was more important than age in explaining our data. In a subgroup of 10 subjects we found that iTBS had no effect on the duration of the ipsilateral silent period suggesting that the reduction in contralateral MEPs was not due to an increase in ongoing transcallosal inhibition. In conclusion, iTBS affects the excitability of excitatory synaptic inputs to pyramidal tract neurones that are recruited by a TMS pulse, both in the stimulated hemisphere and in the contralateral hemisphere. However the circuits affected differ from those influenced by the inhibitory, cTBS, protocol. The implication is that cTBS and iTBS may have different therapeutic targets.


Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin.
Erythropoietin (EPO), a member of the type 1 cytokine superfamily, plays a critical hormonal role regulating erythrocyte production as well as a paracrine/autocrine role in which locally produced EPO protects a wide variety of tissues from diverse injuries. Significantly, these functions are mediated by distinct receptors: hematopoiesis via the EPO receptor homodimer and tissue protection via a heterocomplex composed of the EPO receptor and CD131, the beta common receptor. In the present work, we have delimited tissue-protective domains within EPO to short peptide sequences. We demonstrate that helix B (amino acid residues 58-82) of EPO, which faces the aqueous medium when EPO is bound to the receptor homodimer, is both neuroprotective in vitro and tissue protective in vivo in a variety of models, including ischemic stroke, diabetes-induced retinal edema, and peripheral nerve trauma. Remarkably, an 11-aa peptide composed of adjacent amino acids forming the aqueous face of helix B is also tissue protective, as confirmed by its therapeutic benefit in models of ischemic stroke and renal ischemia-reperfusion. Further, this peptide simulating the aqueous surface of helix B also exhibits EPO's trophic effects by accelerating wound healing and augmenting cognitive function in rodents. As anticipated, neither helix B nor the 11-aa peptide is erythropoietic in vitro or in vivo. Thus, the tissue-protective activities of EPO are mimicked by small, nonerythropoietic peptides that simulate a portion of EPO's three-dimensional structure.


Molecular Machines For The Control Of Transmembrane Transport.
Nature embeds some of its molecular machinery, including ion pumps, within lipid bilayer membranes. This has inspired chemists to attempt to develop synthetic analogues to exploit membrane confinement and transmembrane potential gradients, much like their biological cousins. In this perspective, we outline the various strategies by which molecular machines─molecular systems in which a nanomechanical motion is exploited for function─have been designed to be incorporated within lipid membranes and utilized to mediate transmembrane ion transport. We survey molecular machines spanning both switches and motors, those that act as mobile carriers or that are anchored within the membrane, mechanically interlocked molecules, and examples that are activated in response to external stimuli.


Implications of discoveries from genome-wide association studies in current cardiovascular practice.
Genome-wide association studies (GWAS) have identified several genetic variants associated with coronary heart disease (CHD), and variations in plasma lipoproteins and blood pressure (BP). Loci corresponding to CDKN2A/CDKN2B/ANRIL, MTHFD1L, CELSR2, PSRC1 and SORT1 genes have been associated with CHD, and TMEM57, DOCK7, CELSR2, APOB, ABCG5, HMGCR, TRIB1, FADS2/S3, LDLR, NCAN and TOMM40-APOE with total cholesterol. Similarly, CELSR2-PSRC1-SORT1, PCSK9, APOB, HMGCR, NCAN-CILP2-PBX4, LDLR, TOMM40-APOE, and APOC1-APOE are associated with variations in low-density lipoprotein cholesterol levels. Altogether, forty, forty three and twenty loci have been associated with high-density lipoprotein cholesterol, triglycerides and BP phenotypes, respectively. Some of these identified loci are common for all the traits, some do not map to functional genes, and some are located in genes that encode for proteins not previously known to be involved in the biological pathway of the trait. GWAS have been successful at identifying new and unexpected genetic loci common to diseases and traits, thus rapidly providing key novel insights into disease biology. Since genotype information is fixed, with minimum biological variability, it is useful in early life risk prediction. However, these variants explain only a small proportion of the observed variance of these traits. Therefore, the utility of genetic determinants in assessing risk at later stages of life has limited immediate clinical impact. The future application of genetic screening will be in identifying risk groups early in life to direct targeted preventive measures.


Cost analysis of a patient navigation system to increase screening colonoscopy adherence among urban minorities.
Patient navigation (PN) is being used increasingly to help patients complete screening colonoscopy (SC) to prevent colorectal cancer. At their large, urban academic medical center with an open-access endoscopy system, the authors previously demonstrated that PN programs produced a colonoscopy completion rate of 78.5% in a cohort of 503 patients (predominantly African Americans and Latinos with public health insurance). Very little is known about the direct costs of implementing PN programs. The objective of the current study was to perform a detailed cost analysis of PN programs at the authors' institution from an institutional perspective. In 2 randomized controlled trials, average-risk patients who were referred for SC by primary care providers were recruited for PN between May 2008 and May 2010. Patients were randomized to 1 of 4 PN groups. The cost of PN and net income to the institution were determined in a cost analysis. Among 395 patients who completed colonoscopy, 53.4% underwent SC alone, 30.1% underwent colonoscopy with biopsy, and 16.5% underwent snare polypectomy. Accounting for the average contribution margins of each procedure type, the total revenue was $95,266.00. The total cost of PN was $14,027.30. Net income was $81,238.70. In a model sample of 1000 patients, net incomes for the institutional completion rate (approximately 80%), the historic PN program (approximately 65%), and the national average (approximately 50%) were compared. The current PN program generated additional net incomes of $35,035.50 and $44,956.00, respectively. PN among minority patients with mostly public health insurance generated additional income to the institution, mainly because of increased colonoscopy completion rates.


Arthroscopic Knotless Rotator Cuff Repair With Decellularized Dermal Allograft Augmentation: The "Canopy" Technique.
Repairability and clinical outcomes of full-thickness rotator cuff tears rely on tendon mobility, tissue quality, and subsequent tension on a repair. While repair of rotator cuff tears tend to yield excellent clinical results, poor tissue quality has been an important factor that has hampered successful outcomes. This Technical Note describes a double-row rotator cuff repair using a SpeedBridge configuration with dermal allograft "canopy" augmentation to bolster the repairable but thinned rotator cuff tissue. This technique employs a unique graft fixation strategy to simplify the procedure. This approach could provide surgeons with a great option when faced with mobile but thinned rotator cuff tissue.


Hospital workers discuss Catholic values. Philosophy is the focus in a series of dialogue sessions.
Feedback from staff at Timken Mercy Medical Center in Canton, OH, suggested that they were taking the facility's Catholic identity for granted. Employees did not have a strong understanding of Catholic healthcare philosophy and how it made Timken Mercy different from non-Catholic hospitals. The hospital's administrators sought a solution to this problem. In fall 1992 the hospital began to hold a series of "dialogue sessions" for its staff members on Timken Mercy's philosophy. The first sessions, for managers, were so successful that meetings were added for other hospital workers early the following year. After an opening prayer, the participants in each session discussed points taken from Timken Mercy's statement of philosophy. After the sessions, participants suggested ways the hospital's philosophy might better be embodied in their work lives. Employee morale has improved as a result of the hospital-wide discussion of Catholic healthcare values. A new openness and willingness to grow has been noted in Timken Mercy's staff.


Synthesis, characterization and application of two nucleoside triphosphate analogues, GTPgammaNH(2) and GTPgammaF.
Guanosine triphosphate nucleotide analogues such as GppNHp (also named GMPPNP) or GTPgammaS are widely used to stabilize rapidly hydrolyzing protein-nucleotide complexes and to investigate biochemical reaction pathways. Here we describe the chemical synthesis of guanosine 5'-O-(gamma-amidotriphosphate) (GTPgammaNH(2)) and a new synthesis of guanosine 5'-O-(gamma-fluorotriphosphate) (GTPgammaF). The two nucleotides were characterized using NMR spectroscopy and isothermal titration calorimetry. Chemical shift data on (31)P, (19)F and (1)H NMR resonances are tabulated. For GTPgammaNH(2) the enthalpy of magnesium coordination is DeltaH degrees = 3.9 kcal.mol(-1) and the association constant K(a) is 0.82 mm(-1). The activation energy for GTPgammaNH(2).Mg2+ complex formation is DeltaH++ = 7.8 +/- 0.15 kcal.mol(-1), similar to that for the natural substrate GTP. For GTPgammaF we obtained a similar enthalpy of DeltaH degrees = 3.9 kcal.mol(-1) while the magnesium association constant is only K(a) = 0.2 mm(-1). The application of both guanine nucleotide analogues to the GTP-binding protein Ras was investigated. The rate of hydrolysis of GTPgammaNH(2) bound to Ras protein lay between the rates found for Ras-bound GTPgammaS and GppNHp, while Ras-catalysed hydrolysis of GTPgammaF was almost as fast as for GTP. The two compounds extend the variety of nucleotide analogues and may prove useful in structural, kinetic and cellular studies.


Interactions between malaria and human immunodeficiency virus anno 2014.
Possible pathophysiological, clinical and epidemiological interactions between human immunodeficiency virus (HIV) and tropical pathogens, especially malaria parasites, constitute a concern in tropical areas. Two decades of research have shown that HIV-related immunosuppression is correlated with increased malaria infection, burden, and treatment failure, and with complicated malaria, irrespective of immune status. The recent role out of antiretroviral therapies and new antimalarials, such as artemisinin combination therapies, raise additional concerns regarding possible synergistic and antagonistic effects on efficacy and toxicity. Co-trimoxazole, which is used to prevent opportunistic infections, has been shown to have strong antimalarial prophylactic properties, despite its long-term use and increasing antifolate resistance. The administration of efavirenz, a non-nucleoside reverse transcriptase inhibitor, with amodiaquine-artesunate has been associated with increased toxicity. Recent in vivo observations have confirmed that protease inhibitors have strong antimalarial properties. Ritonavir-boosted lopinavir and artemether-lumefantrine have a synergistic effect in terms of improved malaria treatment outcomes, with no apparent increase in the risk of toxicity. Overall, for the prevention and treatment of malaria in HIV-infected populations, the current standard of care is similar to that in non-HIV-infected populations. The available data show that the wider use of insecticide-treated bed-nets, co-trimoxazole prophylaxis and antiretroviral therapy might substantially reduce the morbidity of malaria in HIV-infected patients. These observations show that those accessing care for HIV infection are now, paradoxically, well protected from malaria. These findings therefore highlight the need for confirmatory diagnosis of malaria in HIV-infected individuals receiving these interventions, and the provision of different artemisinin-based combination therapies to treat malaria only when the diagnosis is confirmed.


Particle clusters at fluid-fluid interfaces: equilibrium profiles, structural mechanics and stability against detachment.
We investigate clustering of particles at an initially flat fluid-fluid interface of surface tension γ under an external force f directed perpendicular to the interface. We employ analytical theory, numerical energy minimization (Surface Evolver) and computational fluid dynamics (the Lattice-Boltzmann method) to study the equilibrium deformation of the interface and structural mechanics of the clusters, in particular at the onset of instability. In the case of incompressible clusters, we find that the equilibrium 3D interface profiles are uniquely determined by the length scale γ/(fn0), where n0 is the particle surface number density, and a non-dimensional shape parameter f2Nn0/γ2. The scaling remains valid in the whole regime of forces f, i.e., even close to the stability limit fcrit. In the cases with an initial hexagonal arrangement of the particles, upon f approaching fcrit, our simulations additionally reveal the emergence of curvature-induced defects and 2D stress anisotropy. We develop stability diagrams in terms of f, N (we study 7 ≤ N ≤ 61), and the contact angle θp at the particles and identify three unstable regimes corresponding to (i) collective detachment of the whole cluster from the interface, (ii) ejection of individual particles, and (iii) both detachment and ejection. We also discuss possible metastable states. Altogether, our results may help in better understanding and controlling the particle interfacial instabilities with potential uses in synthesis of new materials, environmental sciences and microfluidics.


The effect of tourniquet use and hemovac drainage on postoperative hemarthrosis.
Postoperative hemarthrosis is the most common reported complication after arthroscopic knee surgery. The purpose of this study was to determine the effects of hemovac drainage and tourniquet use on the incidence of postoperative hemarthrosis. Sixty patients who had undergone arthroscopic knee surgery were divided into groups based on tourniquet use and whether a drain was used postoperatively. At follow-up, patients had range of motion recorded, and clinical assessment of their hemarthrosis (Grades 0 through 4). Patients who had a hemovac drain used postoperatively, and those patients who did not have a tourniquet used, had fewer hemarthroses and a greater range of motion at all periods of follow-up. We conclude that use of a drain can decrease the incidence of hemarthrosis and allow patients to regain an active range of motion sooner. Also, the routine use of a tourniquet should be avoided because of its correlation with hemarthrosis.


Hardiness in families of young children with asthma.
This paper reports a study (a) to assess whether there are cultural and gender differences in parents' general well-being, sense of coherence and perception of family hardiness when they have a young child with asthma; and (b) to examine the effects of parents' sense of coherence and well-being on family hardiness. Research on hardiness, a resilience factor that fosters adaptation over time, has been widely studied from an individual perspective, but less from the viewpoint of the family unit. In particular, no study was found that assessed how members of a couple interact to affect their family's hardiness. Consideration of this dyadic phenomenon may provide unique insight about how family members interact with each other faced with a challenge, such as the chronic illness of a child. A cross-sectional research design was used with a sample of 137 two-parent families [76 from Iceland and 61 from the United States of America (USA)]. Questionnaires measuring sense of coherence, parents' well-being and family hardiness were used, and demographic data were also collected. The most striking differences in well-being were between mothers and fathers. In addition to a lower average on the total score for the well-being scale, mothers had poorer scores than fathers on the subscales of depression, self-control, vitality, and general health. Family hardiness differed between countries. The regression indicated that the individual's sense of coherence, depression and positive well-being (all actor effects), as well as the partner's anxiety (partner effect) all contributed significantly to family hardiness, as did nationality. Focused interventions for families with young children with asthma should be developed to enable them to feel more confident in using their resources to meet their demands and increase parents' general well-being and family adaptation. Research is needed to develop and test such interventions, particularly with diverse participant samples, encompassing not only a variety of ethnicities, but also a range of children's ages.


A facile and universal method to prepare hydrophilic molecularly imprinted microspheres by encapsulating a polymer in hollow mesoporous silica microspheres.
Hydrophilic molecularly imprinted microspheres (MIP@SiO2) for the adsorption of water-soluble molecules in real aqueous samples were successfully synthesized. In this strategy, a molecular imprinted polymer (MIP) was encapsulated in the hollow core of hollow mesoporous silica (HMS) particles via a 'ship-in-a-bottle' process. As the HMS shell contains plenty of Si-OH groups, the as-prepared microspheres proved to be hydrophilic and could be well dispersed in water. On the other hand, the MIP encapsulated in the HMS could specifically recognize small molecules with good binding efficiency through the mesoporous silica shell. Binding experiments in real aqueous solutions showed that the MIP@SiO2 composites have excellent recognition ability for specific molecules. Thus, MIP@SiO2 are highly promising alternatives to biological receptors with great potential for many analytical applications, such as environmental, food, and clinical analyses and other areas.


[Criteria for choice of an alloy for dental amalgams].
Dental amalgam is still the safest and the most utilized posterior restorative material. The amalgam weakness is the marginal leakage of the filling. This defect is the main source of failure. Creep and corrosion are the most important factors in the marginal destruction mechanism. It's suitable to determine material properties before oral use. Electrochemical methods i.e. corrosion potentials and currents are mainly utilized. In vivo techniques have been developed. Those techniques give us interesting informations on amalgam buccal behaviour in course of time. Amalgam choice is very important: the best one is a High Copper alloy with high corrosion resistance and low creep.


Four hour ambulation after angioplasty is a safe practice method.
During the last 3 decades, there were increasing tendency towards angioplasty because of its benefits. But, this procedure has its acute problems like bleeding and formation of hematoma in the removal place of the sheet. Based on researchers' clinical experiences, patients need a time of 8-12 hours for bed rest after coronary angioplasty. Recognizing desirable time for bed rest after angioplasty and remove the arterial sheet forms the foundation of related researches in the world. Getting out of bed soon after angioplasty, causes more comfortable feelings, less hospitalization period, fewer side effects of prolonged bed rest and less hospitalization expenses. Regarding less time for bed rest after angioplasty, the aim of this study was to assess the effect of the time of getting out of bed after angioplasty on the complications after removing the sheet in coronary angioplasty patients. This was an experimental clinical study conducted in one step and two groups. Samples were included 124 angioplasty patients (62 in each group) who were chosen randomly from the CCU of Shahid Chamran hospital of the Isfahan University of Medical Sciences in 2007. Data were gathered by observing and evaluating the patients, using a questionnaire and a checklist. After angioplasty, patients from the intervention group were taken out of bed in 4 hours and patients from the control group were taken out of bed in 8 hours. After taking out of bed, patients were examined for bleeding and formation of hematoma in the place of taking out the arterial sheet. Data were analyzed using descriptive and inferential statistics via SPSS software. Results showed no meaningful difference between the two groups after getting out of bed (p > 0.05) regarding relative frequency of bleeding (p = 0.50), formation of hematoma (p = 0.34) and average diameter of hematoma (p = 0.39). Results of this study showed that reducing the bed rest time to 4 hours after removing the arterial sheet of size 7 do not increase bleeding and formation of hematoma in the removal place of the sheet. So, those angioplasty patients who do not have critical clinical condition and their vital symptoms are stabilized will be able to get out of bed 4 hours after removing the sheet.


Isothermal amplification of environmental DNA (eDNA) for direct field-based monitoring and laboratory confirmation of Dreissena sp.
Loop-mediated isothermal amplification (LAMP) of aquatic invasive species environmental DNA (AIS eDNA) was used for rapid, sensitive, and specific detection of Dreissena sp. relevant to the Great Lakes (USA) basin. The method was validated for two uses including i) direct amplification of eDNA using a hand filtration system and ii) confirmation of the results after DNA extraction using a conventional thermal cycler run at isothermal temperatures. Direct amplification eliminated the need for DNA extraction and purification and allowed detection of target invasive species in grab or concentrated surface water samples, containing both free DNA as well as larger cells and particulates, such as veligers, eggs, or seeds. The direct amplification method validation was conducted using Dreissena polymorpha and Dreissena bugensis and uses up to 1 L grab water samples for high target abundance (e.g., greater than 10 veligers (larval mussels) per L for Dreissena sp.) or 20 L samples concentrated through 35 μm nylon screens for low target abundance, at less than 10 veligers per liter water. Surface water concentrate samples were collected over a period of three years, mostly from inland lakes in Michigan with the help of a network of volunteers. Field samples collected from 318 surface water locations included i) filtered concentrate for direct amplification validation and ii) 1 L grab water sample for eDNA extraction and confirmation. Though the extraction-based protocol was more sensitive (resulting in more positive detections than direct amplification), direct amplification could be used for rapid screening, allowing for quicker action times. For samples collected between May and August, results of eDNA direct amplification were consistent with known presence/absence of selected invasive species. A cross-platform smartphone application was also developed to disseminate the analyzed results to volunteers. Field tests of the direct amplification protocol using a portable device (Gene-Z) showed the method could be used in the field to obtain results within one hr (from sample to result). Overall, the direct amplification has the potential to simplify the eDNA-based monitoring of multiple aquatic invasive species. Additional studies are warranted to establish quantitative correlation between eDNA copy number, veliger, biomass or organismal abundance in the field.


Infection and failure rates following total hip arthroplasty for septic arthritis: a case-controlled study.
Total hip arthroplasty (THA) is performed as a 2-stage or single stage procedure in patients with a history of septic arthritis of the native hip joint. The decision is based on whether the infection is active or quiescent in the joint. The aim of this study was to compare the outcomes of total hip arthroplasty for septic arthritis of the native hip to a control series of patients treated for primary osteoarthritis of the hip with standard THA. Between March 2000 and March 2013, 18 cases of septic arthritis of the hip treated with THA were retrospectively identified. During the same time period, 18 control cases of THA for degenerative osteoarthritis were identified. Cases and controls were comparable in age, gender, body mass index, type of anaesthesia and American Society of Anesthesiologists score. 11 and 7 cases received 2-stage and single stage total hip arthroplasty respectively for septic arthritis. There was a mean interval of 4 months between 1st and 2nd-stage operations. Cases and controls were followed up for a mean of 70 and 72 months respectively. There was no reinfection or implant failure in the cases, and comparable functional outcomes between cases and controls. Two-stage and single-stage THA for active and quiescent native hip infection respectively, achieved similar outcomes to THA for primary osteoarthritis in controls.


Maitake extracts and their therapeutic potential.
Maitake (Grifola frondosa) is the Japanese name for an edible fungus with a large fruiting body characterized by overlapping caps. It is a premier culinary as well as medicinal mushroom. Maitake is increasingly being recognized as a potent source of polysaccharide compounds with dramatic health-promoting potential. The most recent development is the MD-fraction, a proprietary maitake extract its Japanese inventors consider to be a notable advance upon the preceding D-fraction. The D-fraction, the MD-fraction, and other extracts, often in combination with whole maitake powder, have shown particular promise as immunomodulating agents, and as an adjunct to cancer and HIV therapy. They may also provide some benefit in the treatment of hyperlipidemia, hypertension, and hepatitis.


Ultrasound-Responsive Peptide Nanogels to Balance Conflicting Requirements for Deep Tumor Penetration and Prolonged Blood Circulation.
A series of biological barriers need to be overcome for therapeutic nanocarriers accumulating at the tumor site and uptaken by cancer cells. One strategy is to construct switchable nanocarriers to meet the conflicting requirements for various physiology environments. In this work, besides widely studied endogenous stimuli-responsiveness, an exogenous ultrasound responsiveness was additionally embedded into nanocarriers to balance the conflicting needs of prolonged blood circulation and deep tumor penetration. Polylysine and Pluronic F127 were first coassembled and then cross-linked by genipin to form stable nanogel structure. Subsequently, ICAM-1 antibody was grafted onto the nanogel (designated as GenPLPFT) for active tumor targeting. Upon external sonication, the F127 was shed from GenPLPFT to induce swelling of nanogel with reduced stability and accelerated drug release. In detail, sonication leads to GenPLPF swelling from 329 to 516 nm, while its Young's modulus significantly decreased from 336.78 to 3.93 kPa. Through intravenous injection, relatively rigid GenPLPFT was able to achieve a high level of accumulation at tumor site by active targeting and long-term blood circulation. Moreover, under sonication at the tumor site, GenPLPFT became softer with enhanced deformability to achieve deep tumor penetration. In addition, in vivo studies revealed that GenPLPFT was able to penetrate into the deep area of xenografted tumor with enhanced antitumor efficacy and reduced toxicity. Overall, this peptide nanogel with ultrasound-responsive stiffness demonstrates an effective approach to overcome a series of biological barriers for enhanced deep tumor therapy.


Screening and diagnosis of gestational diabetes mellitus.
American Diabetes Association defines gestational diabetes mellitus (GDM) as diabetes which is diagnosed in the 2nd or 3rd trimester of pregnancy and is not clearly overt diabetes. GDM, if missed or not treated properly can result in maternal and foetal complications, short as well as long term. Screening for overt diabetes, especially for high risk women should be done at the earliest in pregnancy and for GDM, universally at 24-28 weeks of gestation. One step screening by IADPSG (75 gram OGTT), has been recently adopted by most of professional bodies to achieve uniformity. IADPSG criteria have resulted in increase in prevalence of GDM, and consequently increase pressure on health care services as well as on patients. This has resulted in discordance of view on universal adoption of the criteria. Many feel this criteria results in over diagnosis without clear benefits. This brief review will provide the answers to some of the important questions pertaining to screening for GDM.


Designing an audio computer-assisted self-interview (ACASI) system in a multisite trial: a brief report.
To describe the advantages and limitations of an audio computer-assisted self-interview (ACASI) system in a multisite trial with African American couples and to present the steps in designing, testing, and implementing a system. The ACASI system evolved from a paper and pencil interview that was pilot tested. Based on this initial work, the paper and pencil interview was translated into storyboards that were the basis of the development of ACASI system. Storyboards consisted of 1 page per question and provided the programmers with the test of the question, valid responses, and any instructions that were to be read to the participants. Storyboards were further translated into flow diagrams representing each module of the survey and illustrating the skip patterns used to navigate a participant through the survey. Provisions were also made to insert a face-to-face interview, into the ACASI assessment process, to elicit sexual abuse history data, which typically requires specially trained data collectors with active listening skills to help participants reframe and coordinate times, places and, emotionally difficult memories. The ACASI was successfully developed and implemented in the main trial. During an exit interview, respondents indicated that they liked using the ACASI and indicating that they favored it as the method to answer questions. It is feasible to implement an ACASI system in a multisite study in a timely and efficient way.


Telomere length in circulating leukocytes is associated with lung function and disease.
Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (β= -0.0452, p=0.024) as well as COPD (β= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10(-7)), FVC (p=2.07×10(-5)), and FEV1/FVC (p=5.27×10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.


A Cross-sectional Study of the Pattern of Body Image Perception among Female Students of BBM College in Vijayapur, North Karnataka.
Body image is an essential aspect of young girls' self-definition and individual identity which is influenced by various biological, psychological and social factors. Excessive concern about body image, body image misconception are leading to dissatisfaction, disturbed eating patterns, affecting the nutritional status and also leading to depression and anxiety disorders. This concept of body image has been less explored in Indian context, especially among young girls. The objectives of the study were to assess the body image perception among young college going girls, using a visual analog scale and to compare body image perception and satisfaction with their BMI levels and weight changing methods adopted. An exploratory cross-sectional study was conducted among 63 female students studying BBM course at a private commerce institution in Vijayapur city. Data was collected using a self administered questionnaire containing details of basic socio-demographic information and a validated visual analogue scale. Height was measured by Seca Stadiometer, weight was measured using Digital weighing machine and Body Mass Index levels were calculated. Percentages were calculated for descriptive variables. Chi-square test was applied for analysing categorical variables. Spearman Rank correlation test was applied for analysing ordinal data. A 39.7% of participants were underweight and 15.9% were overweight/obese. Majority of underweight and overweight girls (72% and 89%, respectively) perceived themselves as normal weight. Body image satisfaction of participants was found to be significantly associated with their body image perception, mothers' educational status and also with relatives' and peer group's opinions about their body weight. Unhealthy weight changing patterns like skipping meals (13%), increasing quantity and frequency of meals (17%) were reported among study participants. This exploratory study highlights the gap between young girls' body image perception and their BMI levels, indicating body image misconception. Lower literacy level of mothers and opinions of relatives and friends significantly influenced body image satisfaction among study participants. Higher percentage of underweight (39.7%) coupled with unhealthy weight changing patterns reportedly adopted by participants (30%) indicates need for further research on this issue, to help inform public health nutrition programmes.


Clinical Observation and Analysis of Thyroglossal Duct Cyst Carcinoma: A Report of 5 Cases.
Thyroglossal duct cyst carcinoma (TGDCCa) is a rare condition with only approximately 300 cases reported to date. There is a lack of comprehensive reporting on its clinical manifestations, ultrasound, contrast-enhanced computed tomography, magnetic resonance imaging (MRI) features, immunophenotyping, procedure, and prognosis following modified Sistrunk's procedure. This study aimed to address these gaps by analyzing and summarizing the clinical features of 5 cases of papillary carcinoma arising in thyroglossal duct cysts (TGDC).Five patients with papillary carcinoma in TGDC treated by modified Sistrunk's procedure were included. Their clinical manifestation, physical examination findings, iconography, pathological findings, treatment, and outcomes were analyzed in aiding the diagnosis and treatment of TGDCCa. Immunohistochemistry was used to confirm the papillary carcinoma subtype. The BRAFV600E mutation was detected in 2 patients. No evidence of cancer recurrence, distant metastases, and malignant changes in the thyroid was found after a mean follow-up of 29.8 months.The management of TGDCCa with papillary carcinoma in low-risk patients can be accomplished by performing a modified Sistrunk's procedure along with a regular follow-up imaging of the thyroid and neck. Although postoperative pathological diagnosis is the gold standard for diagnosis, it is equally crucial to comprehend the clinical manifestations and auxiliary diagnostic techniques before surgical intervention.


The novel carboxamide analog ITR-284 induces caspase-dependent apoptotic cell death in human hepatocellular and colorectal cancer cells.
We have previously reported that ITR-284, a potent carboxamide-derived anticancer agent, induced apoptosis in leukemia cells. However, there are no reports showing that ITR-284 inhibits human hepatocellular and colorectal cancer cells. In this study, we investigated the antiproliferative effects and apoptotic induction of ITR-284 on various types of human hepatocellular and colorectal cancer cells in vitro. The growth inhibition effect of ITR-284 on cancer cells was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay. Cell morphology was examined under a phase-contrast microscope. The activities of caspase-3, -8 and -9 were determined by caspase colorimetric assay. ITR-284 reduced the cell viability in human hepatocellular cancer cells (Hep G2, Hep 3B, SK-HEP-1 and J5) and colorectal cancer cells (HT 29, COLO 205, HCT 116 and SW 620). ITR-284 had highly selective effects on Hep 3B and COLO 205 cells. ITR-284 stimulated morphological changes of Hep 3B and COLO 205 cells. The activation of caspase-3, -8 and -9 contributed to ITR-284-induced apoptosis. ITR-284-triggered growth inhibition was significantly attenuated by the inhibitors of caspase-3, -8 and -9 in Hep 3B and COLO 205 cells. ITR-284 induced apoptosis in Hep 3B and COLO 205 cells through the caspase cascade-dependent signaling pathway.


Assessing the effect of pregnancy stage on milk composition of dairy cows using mid-infrared spectra.
Changes in milk production traits (i.e., milk yield, fat, and protein contents) with the pregnancy stage are well documented. To our knowledge, the effect of pregnancy on the detailed milk composition has not been studied so far. The mid-infrared (MIR) spectrum reflects the detailed composition of a milk sample and is obtained by a nonexhaustive and widely used method for milk analysis. Therefore, this study aimed to investigate the effect of pregnancy on milk MIR spectrum in addition to milk production traits (milk yield, fat, and protein contents). A model including regression on the number of days pregnant was applied on milk production traits (milk yield, fat, and protein contents) and on 212 spectral points from the MIR spectra of 9,757 primiparous Holstein cows from Walloon herds. Effects of pregnancy stage were expressed on a relative scale (effect divided by the squared root of the phenotypic variance); this allowed comparisons between effects on milk traits and on 212 spectral points. Effect of pregnancy stage on production traits were in line with previous studies indicating that the model accounted well for the pregnancy effect. Trends of the relative effect of the pregnancy stage on the 212 spectral points were consistent with known and observed effect on milk traits. The highest effect of the pregnancy was observed in the MIR spectral region from 968 to 1,577 cm-1. For some specific wavenumbers, the effect was higher than for fat and protein contents in the beginning of the pregnancy (from 30 to 90 or 120 d pregnant). In conclusion, the effect of early pregnancy can be observed in the detailed milk composition through the analysis of the MIR spectrum of bovine milk. Further analyses are warranted to explore deeply the use of MIR spectra of bovine milk for breeding and management of dairy cow pregnancy.


[Combined low-intensity laser radiation in renal tuberculosis].
Combined external radiation in the projection of the kidneys and intravascular laser blood radiation by applying an AZOR-2K apparatus were used in the combined treatment of 54 patients with tuberculosis of the urinary system. Analysis of the biochemical and immunological parameters of the patients' peripheral blood before and 3 weeks and 3 months after the combined treatment provided evidence suggesting a decrease in the magnitude of lipid peroxidation, an increase in the antioxidative status, and a reduction in the level of metabolites that affect on the development of the intoxication syndrome. The clinical findings suggest that the combined treatment has a beneficial impact on the course of renal tuberculosis, as appeared as better functional indices of urinary organs.


[Erythrocyte ultrastructure in norm and pathology: morphological phenomena and clinical correlations].
Using transmission electron microscopy, erythrocyte ultrastructure in norm and pathology was described. Among the morphological phenomena, most common were local and extensive erythrocyte plasmalemmal defects in the form of its loosening, thinning, consolidation and thickening, rupture, fragmentation, exfoliation from stroma with the formation of cavities. Plasmalemmal destruction may be accompanied with the formation of micro- and macroexovesicles, some of which lose the connection with the erythrocyte. Morphological signs of erythrocyte stromal disorganization included irregular distribution of hemoglobin granules with the formation of the regions of increased and decreased electron density, loosening of the internal structure up to the formation of cavities, as well as endovesicles, partially containing small or large osmiophilic particles. It was shown that in pathological processes of different genesis (malignant tumors, chronic bronchitis, burn trauma, schizophrenia) ultrastructural changes of erythrocytes have typical character.


AML1A and AML1B can transactivate the human IL-3 promoter.
The AML1 gene encodes several transcription factors, including AML1A and AML1B, which bind to DNA via a TGT/cGGT consensus sequence that is found in several promoters, including the human IL-3 promoter. We performed cotransfection experiments in T cells, and demonstrated that although AML1A lacks a putative transactivation domain, it can transactivate the IL-3 promoter nearly as effectively as AML1B, a known activator. A consensus AML1 binding site (TGTGGT), located in the previously identified DNase I footprint region A of the human IL-3 promoter (extending from bp -165 to -128), and a sequence similar to the consensus binding site (TGTGGG), located in footprint region B (bp -55 to -42), specifically bind AML1 proteins in gel shift assays. The affinity for the TGTGGG sequence was much less than that for the TGTGGT sequence, and mutating the TGTGGG sequence did not alter the IL-3 promoter activity, whereas mutation of the consensus binding site decreased the basal promoter activity and nearly eliminated transactivation by AML1A and AML1B. The AML1/ETO fusion protein, generated by the t(8;21) translocation, repressed IL-3 promoter activity, although the AML1 portion of AML1/ETO (amino acids 1-177) lacked transcriptional regulatory activity and did not bind to DNA in vitro. The 60- to 177-amino acid portion of AML1 readily bound DNA, suggesting that the first 59 amino acids may function as an inhibitory domain for DNA binding. Demonstration of the transactivation by AML1A and localization of a putative inhibitory binding domain suggest additional complexity within this family of transcription factors.


Biopsy-Proven BK Virus-Associated Nephropathy: Clinico-Pathologic Correlations.
Our objective was to study the clinico-pathologic correlations in BK virus nephropathy. We conducted a retrospective study of all patients with biopsy-proven polyoma (BK) virus infection. We compared their survival and renal outcomes versus BK virus-negative patients with biopsy-proven graft rejection. Histopathologic characterization by a blinded nephropathologist was performed. BK nephropathy was found in 10 patients biopsied for graft dysfunction. All virus-positive patients received antithymocyte globulin induction therapy compared with only 59.3% of the BK-negative group (P = .06). The percentage of patients in the BK-negative group who received acyclovir was significantly higher than that in the BK-positive group (P = .01). After a mean observation period of 6.8 ± 3.2 years, 70% of the BK group had functioning grafts compared with 68% in the BK-negative group (P = .9) with similar 3-year graft survival in the 2 groups (80% and 90%; P = .8). Within the BK group, graft survival was better in the older group (P = .005) and in those with deceased donor kidney grafts (P = .016). Patients in the BK-negative group were heavier (mean weight of 64.3 ± 12.1 vs 46.7 ± 20.6 kg; P = .003). None of the histopathologic features studied had any effect on renal prognosis. The risk factors for developing BK nephropathy were use of antithymocyte globulin, lower weight, and not using acyclovir as early prophylaxis. Within the BK nephropathy group, better graft survival was observed in deceased donor kidney recipients and in older patients. The viral load and polyoma virus nephropathy stage did not affect graft survival in this small sample study.


Evidence of genetic susceptibility to Chlamydia trachomatis-induced pelvic inflammatory disease in the pig-tailed macaque.
The macaque model of chlamydial pelvic inflammatory disease (PID) demonstrates individual variability in the time of onset of intrapelvic adhesions. Some animals develop adhesions rapidly, within 2 weeks after a single tubal inoculation with Chlamydia trachomatis, while in others, adhesions are not observed until 2 weeks after a second tubal inoculation. To test whether this variability correlates with major histocompatibility complex (MHC) class I haplotype, we used macaque alloantisera and mouse anti-HLA monoclonal antibodies to determine the MHC class I haplotypes of 44 C. trachomatis-infected macaques (Macaca nemestrina). Macaques developing gross tubal adhesions after the first chlamydial inoculation were classified as susceptible (n = 29), while those not developing adhesions until after the second chlamydial inoculation were classified as relatively resistant (n = 15), to adhesion formation. Three antibody specificities correlated with susceptibility (odds ratio [OR] 5.2, P < 0.01; OR 6.1 and 4.3, P < 0.05), and two correlated with relative resistance to adhesions (OR 0.1, P < 0.05; OR 0.2, P < 0.01). Because several of these antibodies are cross-reactive, as many as five different MHC class I alleles (three increasing and two decreasing ORs) or as few as two different MHC class I alleles (one increasing and one decreasing OR) could be correlated with risk of adhesion formation. We conclude that in macaques, susceptibility or relative resistance to rapid formation of tubal adhesions is correlated with expression of MHC class I alleles, consistent with reports of MHC class I restriction of chlamydial immunopathology in humans.


Electrically powered motions of toron crystallites in chiral liquid crystals.
Malleability of metals is an example of how the dynamics of defects like dislocations induced by external stresses alters material properties and enables technological applications. However, these defects move merely to comply with the mechanical forces applied on macroscopic scales, whereas the molecular and atomic building blocks behave like rigid particles. Here, we demonstrate how motions of crystallites and the defects between them can arise within the soft matter medium in an oscillating electric field applied to a chiral liquid crystal with polycrystalline quasi-hexagonal arrangements of self-assembled topological solitons called "torons." Periodic oscillations of electric field applied perpendicular to the plane of hexagonal lattices prompt repetitive shear-like deformations of the solitons, which synchronize the electrically powered self-shearing directions. The temporal evolution of deformations upon turning voltage on and off is not invariant upon reversal of time, prompting lateral translations of the crystallites of torons within quasi-hexagonal periodically deformed lattices. We probe how these motions depend on voltage and frequency of oscillating field applied in an experimental geometry resembling that of liquid crystal displays. We study the interrelations between synchronized deformations of the soft solitonic particles and their arrays, and the ensuing dynamics and giant number fluctuations mediated by motions of crystallites, five-seven defects pairs, and grain boundaries in the orderly organizations of solitons. We discuss how our findings may lead to technological and fundamental science applications of dynamic self-assemblies of topologically protected but highly deformable particle-like solitons.