Optical coherence tomography imaging of the basal ganglia: feasibility and brief review.
Optical coherence tomography (OCT) is a promising medical imaging technique that uses light to capture real-time cross-sectional images from biological tissues in micrometer resolution. Commercially available optical coherence tomography systems are employed in diverse applications, including art conservation and diagnostic medicine, notably in cardiology and ophthalmology. Application of this technology in the brain may enable distinction between white matter and gray matter, and obtainment of detailed images from within the encephalon. We present, herein, the in vivo implementation of OCT imaging in the rat brain striatum. For this, two male 60-day-old rats (Rattus norvegicus, Albinus variation, Wistar) were stereotactically implanted with guide cannulas into the striatum to guide a 2.7-French diameter high-definition OCT imaging catheter (Dragonfly™, St. Jude Medical, USA). Obtained images were compared with corresponding histologically stained sections to collect imaging samples. A brief analysis of OCT technology and its current applications is also reported, as well as intra-cerebral OCT feasibility on brain mapping during neurosurgical procedures.


A new diffractometer for diffuse scattering studies on the ID28 beamline at the ESRF.
A new diffractometer is now available to the general user community at the ESRF. The new diffractometer is a side station of the high-resolution inelastic X-ray scattering spectrometer on beamline ID28 and is located in the same experimental hutch. Both instruments can be operated simultaneously. The new diffractometer combines a fast and low-noise hybrid pixel detector with a variable diffraction geometry. The beam spot on the sample is 50 µm × 50 µm, where focusing is achieved by a combination of Be lenses and a KB mirror. Wavelengths from 0.5 to 0.8 Å can be used for the diffraction experiments. The setup is compatible with a variety of sample environments, allowing studies under non-ambient conditions. The diffractometer is optimized to allow a rapid survey of reciprocal space and diffuse scattering for the identification of regions of interest for subsequent inelastic scattering studies, but can also be employed as a fully independent station for structural studies from both powder and single-crystal diffraction experiments. Several software packages for the transformation and visualization of diffraction data are available. An analysis of data collected with the new diffractometer shows that the ID28 side station is a state-of-the-art instrument for structural investigations using diffraction and diffuse scattering experiments.


A novel neural-network model for deriving standard 12-lead ECGs from serial three-lead ECGs: application to self-care.
Synthesis of the 12-lead ECG has been investigated in the past decade as a method to improve patient monitoring in situations where the acquisition of the 12-lead ECG is cumbersome and time consuming. This paper presents and assesses a novel approach for deriving 12-lead ECGs from a pseudoorthogonal three-lead subset via generic and patient-specific nonlinear reconstruction methods based on the use of artificial neural-networks (ANNs) committees. We train and test the ANN on a set of serial ECGs from 120 cardiac inpatients from the intensive care unit of the Cardiology Hospital of Lyon. We then assess the similarity between the synthesized ECGs and the original ECGs at the quantitative level in comparison with generic and patient-specific multiple-regression-based methods. The ANN achieved accurate reconstruction of the 12-lead ECGs of the study population using both generic and patient-specific ANN transforms, showing significant improvements over generic (p -value < or = 0.05) and patient-specific ( p-value < or = 0.01) multiple-linear-regression-based models. Consequently, our neural-network-based approach has proven to be sufficiently accurate to be deployed in home care as well as in ambulatory situations to synthesize a standard 12-lead ECG from a reduced lead-set ECG recording.


Hema-seq reveals genomic aberrations in a rare simultaneous occurrence of hematological malignancies.
Co-occurrence of multiple myeloma and acute myelogenous leukemia is rare, with both malignancies often tracing back to multipotent hematopoietic stem cells. Cytogenetic techniques are the established baseline for diagnosis and characterization of complex hematological malignancies. In this study, we develop a workflow called Hema-seq to delineate clonal changes across various hematopoietic lineages through the integration of whole-genome sequencing, copy-number variations, cell morphology, and cytogenetic aberrations. In Hema-seq, cells are selected from Wright-stained slides and fluorescent probe-stained slides for sequencing. This technique therefore enables direct linking of whole-genome sequences to cytogenetic profiles. Through this method, we mapped sequential clonal alterations within the hematopoietic lineage, identifying critical shifts leading to myeloma and acute myeloid leukemia (AML) cell formations. By synthesizing data from each cell lineage, we provided insights into the hematopoietic tree's clonal evolution. Overall, this study highlights Hema-seq's capability in deciphering genomic heterogeneity in complex hematological malignancies, which can enable better diagnosis and treatment strategies.


[Value of colon sonography within the scope of surgical diagnosis].
The sensitivity, specificity, and predictable potential of colon sonography were determined by comparison between sonographic, colonoscopic, radiological, and surgically secured findings. Also compared were sonographic colon findings obtained from unprepared patients (n = 74) with those obtained from patients prepared by means of orthograde mannitol irrigations (n = 53). No major differences were found to exist between both groups. Indications for colon sonography in the context of surgical diagnosis are outlines on the basis of the above results.


The intake of energy and selected nutrients by thai urban sedentary workers: an evaluation of adherence to dietary recommendations.
Rapid changes in Thailand's nutrition and lifestyles have led to increasing diet-related pathologies among people with sedentary occupations. This study examines the extent to which the dietary intake of nutrients and energy by a sample of Thai sedentary workers conforms to the Thai Dietary Reference Intakes (Thai DRIs). The nutrients and energy intake estimates were based on self-reported information collected with a single 24-hour dietary recall and nonweighed 2-day food record. The study participants were Thai adults aged 20-50 years employed in sedentary occupations. A convenience sample of 215 healthy individuals (75 males and 140 females) was based on four randomly selected worksites in the Bangkok metropolitan area. For male participants, the study found a median energy intake of 1,485 kcal/day, with 54.4% of energy coming from carbohydrate, 15.9% from protein, and 29.6% from fat. Females' median energy intake was 1,428 kcal/day, 56% of which came from carbohydrate, 16.2% from protein, and 28.6% from fat. Both genders showed insufficient intake of fiber and most micronutrients. This study provides the material for preventive public health interventions focusing on nutrition-related diseases affecting Thailand's rapidly growing sedentary workforce.


Neurochemical effects of nicotine on glutamate and GABA mechanisms in the rat brain.
The effects of nicotine on gamma-aminobutyric acid (GABA) and glutamate mechanisms were studied in several rat brain regions both in vivo and in vitro. In vivo acute intermittent injections of nicotine decrease GABA utilization in the hypothalamus and glutamate levels within the nucleus caudatus and the subcortical limbic forebrain (mainly tuberculum olfactorium and nucleus accumbens). Glutamic acid decarboxylase activity was slightly increased in several regions, when the rats were treated with a single convulsant dose of nicotine and killed at the moment of the convulsions but it was not affected by a single injection nor by intermittent acute administration of non-convulsant doses of nicotine. In vitro nicotine elicited release of L-[3H]glutamate from synaptosomal preparations obtained from the frontoparietal cortex, nucleus caudatus and hypothalamus. The effect was dose-dependent and it was not blocked by mecamylamine. It was also Ca2+ independent. The possibilities are discussed that the decreased GABA utilization in the hypothalamus may be related to certain neuroendocrine actions of nicotine and that the nicotine-induced glutamate release might be involved in some of the physiological and toxicological effects of nicotine.


Positive regulation of Bacillus subtilis ackA by CodY and CcpA: establishing a potential hierarchy in carbon flow.
Conversion of pyruvate to acetate via the phosphotransacetylase-acetate kinase pathway generates ATP and is a major overflow pathway under conditions of carbon and nitrogen excess. In Bacillus subtilis, this pathway is positively regulated by CcpA, a global regulator of carbon metabolism genes. Transcription of the acetate kinase gene (ackA) proved to be activated as well by a second global regulatory protein, CodY. Expression of an ackA-lacZ fusion was reduced in a codY mutant strain. CodY was found to bind in vitro to two sites in the ackA promoter region and to stimulate ackA transcription in a run-off transcription assay. This is the first known case of direct positive regulation by CodY. CodY and CcpA were found to bind to neighbouring sites and their effects were additive both in vivo and in vitro. Surprisingly, positive regulation by CodY, unlike repression, responded primarily to only one type of effector molecule. That is, branched-chain amino acids (BCAAs) served as more potent co-activators of CodY-dependent ackA transcription than did GTP. Given the roles of CcpA and CodY in regulating genes whose products determine the metabolic fate of pyruvate, these two proteins may act together to mediate a hierarchical conversion of pyruvate to its many potential products.


Titanium elastic nailing in diaphyseal femoral fractures of children below six years of age.
To report the clinical and radiographic results of titanium elastic nail (TEN) in diaphyseal femoral fractures of children below age of six years. A retrospective analysis of 27 diaphyseal femoral fractures in children younger than six years treated with TEN between 2005 and 2015 was conducted. Patients were immobilized in a cast for 5 wk and the nails were removed from 6 to 12 wk after surgery. Twenty-four cases were clinically and radiographically re-evaluated using the Flynn's scoring criteria, focusing on: Limb length discrepancy, rotational deformity, angulation, hip and knee range of motion (ROM), functional status, complications, and parent's satisfaction. Sixteen males and eight females with a mean age of 3.2 years at the time of treatment were re-evaluated at an average follow-up of 58.9 mo. No cases of delayed union were observed. The mean limb lengthening was 0.3 cm. Four cases experienced limb lengthening greater than 1 cm and always minor than 2 cm. Twelve point five percent of the cases showed an angulation < 10°. Complete functional recovery (hip and knee ROM, ability to run and jump on the operated limb) occurred in 95.7% of cases. Complications included two cases of superficial infection of the TEN entry point, one case of refracture following a new trauma, and one TEN mobilization. According to the Flynn's scoring criteria, excellent results were obtained in 79.2% of patients and satisfactory results in the remaining 20.8%, with an average parent's satisfaction level of 9.1/10. TEN is as a safe, mini-invasive and surgeon-friendly technique and, considering specific inclusion criteria, it represents a useful and efficacy option for the treatment of diaphyseal femoral fractures even in patients younger than six years of age.


Practical and Asymmetric Reductive Coupling of Isoquinolines Templated by Chiral Diborons.
We herein describe a chiral diboron-templated highly diastereoselective and enantioselective reductive coupling of isoquinolines that provided expedited access to a series of chiral substituted bisisoquinolines in good yields and excellent ee's under mild conditions. The method enjoys a broad substrate scope and good functional group compatibility. Mechanistic investigation suggests the reaction proceeds through a concerted [3,3]-sigmatropic rearrangement.


Antagonistic effects of interleukin 6 and G-CSF in the later stage of human granulopoiesis in vitro.
The effect of recombinant human interleukin 6 (rhIL-6) on the in vitro growth of human bone marrow myeloid progenitors (granulocyte-macrophage colony-forming units, CFU-GM) was investigated. Recombinant human IL-6 by itself did not induce colony formation. When rhIL-6 at various concentrations was added to the CFU-GM colony cultures containing recombinant human granulocyte colony-stimulating factor (rhG-CSF) or recombinant human granulocyte-monocyte/macrophage colony-stimulating factor (rhGM-CSF), rhIL-6 significantly suppressed the colony formation induced by rhG-CSF, but not by rhGM-CSF. This suppressive effect of rhIL-6 on rhG-CSF-induced, but not rhGM-CSF-induced colony formation was confirmed by using an MY10(+)-cell-enriched population. Neither interleukin 3 nor interleukin 1 alpha suppressed the growth of myeloid progenitors. The preincubation of bone marrow cells with rhIL-6 for a short time (30 min) resulted in a reduction of colonies induced by rhG-CSF, but not by rhGM-CSF. The suppressive effect of rhIL-6 on rhG-CSF-induced colony formation was not observed when the cells were preincubated together with rhG-CSF at a high ratio of rhG-CSF to rhIL-6. The rhIL-6-mediated suppressive effect was further confirmed by blocking the effect by the anti-IL-6 antibody. These results suggest antagonistic interaction between IL-6 and G-CSF in the later differentiation of myeloid progenitors.


Coriander essential oil composition from two genotypes grown in different environmental conditions.
The objective was to study the essential oil composition of coriander fruits in plants growing in environments differing in soil conditions and weediness level. Factorial field experiments were conducted in two locations from the Rolling Pampas, Argentina, and two coriander landraces (European and Argentinean) were tested under two levels of nitrogen fertilization and weediness. Data were evaluated with uni- and multivariate techniques. The variation in the oil composition was related to the relative proportion of the constituents and not to the presence/absence of a particular component. Weather conditions in 1997 favored linalool and camphor in both landraces. Location, fertilization, and weediness also affected the chemical profile. The European landrace showed a more stable concentration of the major components than the Argentinean landrace. These results, which show the relationships between some environmental conditions and the essential oil composition, are useful in the development of innovative strategies aimed to improve oil composition and to manage crop pests.


Propionibacterium Acnes Infection of a Metacarpophalangeal Joint Arthroplasty.
Neglected and underestimated in the past, Propionibacterium acnes is currently the most prevalent organism associated with deep prosthetic infections around the shoulder. Surprisingly, it has never been reported as a cause of infection in the hand. Here we report a case of a late presentation of a P. acnes infection in a metacarpophalangeal joint replacement, resulting in chronic low-grade pain with movement. The patient underwent a 2-stage revision, with initial removal of the prosthesis. Positive cultures for P. acnes required 15 days of extended incubation. The patient subsequently had 6 weeks of oral antibiotics followed by a second-stage revision with a Silastic implant.


The effect of habitat and human disturbance on the spatiotemporal activity of two urban carnivores: The results of an intensive camera trap study.
With rising urbanization, the presence of urban wildlife is becoming more common, increasing the need for wildlife-friendly spaces in urban planning. Despite this, understanding is limited to how wildlife exploits urban environments and interacts with human populations, and this is vital to our ability to manage and conserve wildlife in urban habitats. Here, we investigate how two urban mammal species, the red fox (Vulpes vulpes) and the European badger (Meles meles), exploit urban environments. Using intensive camera trap surveys, we assessed how habitat and human disturbance influenced the spatiotemporal activity of these species across south-west London. Firstly, we found elevated activity levels of both species at boundaries and within built-up areas, suggesting movement paths follow anthropogenic features. However, badgers were most active in woodland, indicating the importance of high cover habitats suitable for setts and foraging. Secondly, we found badger activity levels were negatively affected by human activity, whilst foxes were unaffected. Further investigation suggested foxes may adapt their activity patterns to avoid human disturbance, with badger activity patterns less plastic. Whilst the results of this study are useful for both the conservation and management of urban wildlife populations, these results also show potential factors which either facilitate or limit wildlife from fully exploiting urban environments.


Fe(III) oxide reduction and carbon tetrachloride dechlorination by a newly isolated Klebsiella pneumoniae strain L17.
To isolate an iron-reducing bacterium and examine its ability of Fe(III) oxide reduction and dechlorination. A fermentative facultative anaerobe, strain L17 isolated from subterranean sediment, can reduce Fe(III) oxides and carbon tetrachloride (CT). It was identified as Klebsiella pneumoniae by 16S rRNA sequence analysis. Strain L17 can metabolize fermentable substrates such as citrate, glycerol, glucose and sucrose coupled with the reduction of hydrous ferric oxide, goethite, lepidocrocite and hematite. Fe(III) reduction was influenced by crystal structure of Fe(III) oxide, type of fermentable substrate, metabolic status of the strain, and significantly enhanced by addition of anthraquinone-2,6-disulfonate (AQDS). Strain L17 could dechlorinate CT to chloroform, and the rate was accelerated in the presence of Fe(III) oxide and AQDS. Biotic dechlorination by strain L17 and abiotic dechlorination by sorbed Fe(II) were proposed as the two main mechanisms. AQDS might accelerate the dechlorination by transferring electrons from strain L17 to Fe(III) oxide and CT. K. pneumoniae L17 can reduce Fe(III) oxides and CT. The two reductions can occur simultaneously, and be significantly promoted by AQDS. This is the first report of a strain of K. pneumoniae capable of reducing Fe(III) oxides and CT. As a strain of environmental origin, strain L17 may have the potential for bioremediation of chlorinated compound-contaminated sites.


New pathophysiological aspects of growth and prevention of kidney stones.
Kidney stones probably grow during crystalluria by crystal sedimentation and aggregation (AGN) on stone surfaces. This process has to occur within urinary transit time (UT) through the kidney before crystals are washed out by diuresis. To get more information, we studied by spectrophotometry the formation and AGN of Ca oxalate (Ca Ox) crystals which were directly produced in urine of 30 stone patients and 30 controls by an oxalate (Ox) titration. Some tests were also performed after removing urinary macromolecules (UMs) by ultrafiltration. To induce rapid crystallization, high Ox additions (0.5-0.8 mM) were necessary. The most important finding was retardation of crystal AGN by UM. In urine of 63% of controls but only 33% of patients, no AGN was observed during an observation of 60 minutes (P < 0.05). Also growth and sedimentation rate of crystals were significantly reduced by UM. For stone metaphylaxis, especially for posttreatment residuals, avoiding dietary Ox excesses to prevent crystal formation in the kidney and increasing diuresis to wash out crystals before they aggregate are recommended.


Laryngoscopic and stroboscopic signs in the diagnosis of vocal fold paresis.
To identify strobolaryngoscopic findings significant in the diagnosis of paresis. Retrospective cohort study. Fellowship-trained laryngologists reviewed 34 videostroboscopic examinations (24 with paresis, eight without paresis, two repeat). They indicated presence or absence of paresis, including side and type, degree of confidence in diagnosis, and ranked clinical findings that influenced diagnosis by order of importance. Fleiss's κ was used to assess inter-rater agreement for paresis presence, side, and type. Clinical findings compelling in diagnosis were tabulated and described. Confidence levels for side and type were compared by analysis of variance/Kruskal-Wallis tests and post hoc pairwise comparisons. Thirty-one laryngologists completed the review. Inter-rater agreement on presence or absence of paresis was fair at 0.334 (Fleiss's κ). Fourteen examinations were diagnosed with paresis by >70% of raters and considered strong paresis-candidate exams. Diagnosis of paresis side and type were inconsistent, although with statistically significant differences in confidence ratings (unilateral vs. bilateral, recurrent laryngeal nerve [RLN] vs. superior laryngeal nerve [SLN], RLN vs. mixed RLN/SLN). Laryngoscopic and stroboscopic findings with the strongest association with paresis were vocal fold motion anomalies, vocal fold degeneration, glottic insufficiency, and mucosal wave anomalies. Most laryngologists use strobolaryngoscopy for diagnosis of paresis. Although certain clinical findings were found to be associated with diagnosis, most commonly vocal fold motion anomalies, these varied among raters, especially when determining sidedness and nerve involvement. Future studies should expand the discussion and consideration of strobolaryngoscopic factors and adjunct functional and objective measures to develop a heuristic algorithm for diagnosis of paresis. 4. Laryngoscope, 127:2100-2105, 2017.


A Method for Analyzing the Impact of Intra-System and Inter-System Interference on DME Based on Queueing Theory.
In order to use Distance Measuring Equipment (DME) properly, the impact of intra-system and inter-system electromagnetic interference must be analyzed firstly. However, the error of interference analysis using present methods based on pulse overlap is large when there are more aircraft. The aim of this article is to study a method of analyzing interference on DME whether the number of aircraft is small or not. According to the flow chart of DME signal, we studied the limitations of present methods; then constructed a model of analyzing the collision between duration of desired signal and dead time of receiver based on M/M/1/0 queueing system. Combing this model with other methods, we present a analytic model of analyzing intra-system and inter-system interference on DME. Using this analytic model, we analyzed reply efficiency (RE) and capacity of DME under intra-system and Joint Tactical Information Distribution System (JTIDS) interference. The result shows that the calculation for the probability of overlap between DME dead time and subsequent signals using queueing model agrees well with simulation. Consequently, the analytic model is more accurate than using a single method to analyze interference on DME.


Manganese ions enhance mitochondrial H2O2 emission from Krebs cycle oxidoreductases by inducing permeability transition.
Manganese-induced toxicity has been linked to mitochondrial dysfunction and an increased generation of reactive oxygen species (ROS). We could recently show in mechanistic studies that Mn2+ ions induce hydrogen peroxide (H2O2) production from the ubiquinone binding site of mitochondrial complex II (IIQ) and generally enhance H2O2 formation by accelerating the rate of superoxide dismutation. The present study with intact mitochondria reveals that manganese additionally enhances H2O2 emission by inducing mitochondrial permeability transition (mPT). In mitochondria fed by NADH-generating substrates, the combination of Mn2+ and different respiratory chain inhibitors led to a dynamically increasing H2O2emission which was sensitive to the mPT inhibitor cyclosporine A (CsA) as well as Ru-360, an inhibitor of the mitochondrial calcium uniporter (MCU). Under these conditions, flavin-containing enzymes of the mitochondrial matrix, e.g. the mitochondrial 2-oxoglutaratedehydrogenase (OGDH), were major sources of ROS. With succinate as substrate, Mn2+ stimulated ROS production mainly at complex II, whereby the applied succinate concentration had a marked effect on the tendency for mPT. Also Ca2+ increased the rate of H2O2 emission by mPT, while no direct effect on ROS-production of complex II was observed. The present study reveals a complex scenario through which manganese affects mitochondrial H2O2 emission: stimulating its production from distinct sites (e.g. site IIQ), accelerating superoxide dismutation and enhancing the emission via mPT which also leads to the loss of soluble components of the mitochondrial antioxidant systems and favors the ROS production from flavin-containing oxidoreductases of the Krebs cycle.


Protein fragment swapping: a method for asymmetric, selective site-directed recombination.
This article presents a new approach to site-directed recombination, swapping combinations of selected discontiguous fragments from a source protein in place of corresponding fragments of a target protein. By being both asymmetric (differentiating source and target) and selective (swapping discontiguous fragments), our method focuses experimental effort on a more restricted portion of sequence space, constructing hybrids that are more likely to have the properties that are the objective of the experiment. Furthermore, since the source and target need to be structurally homologous only locally (rather than overall), our method supports swapping fragments from functionally important regions of a source into a target "scaffold" (for example, to humanize an exogenous therapeutic protein). A protein fragment swapping plan is defined by the residue position boundaries of the fragments to be swapped; it is assessed by an average potential score over the resulting hybrid library, with singleton and pairwise terms evaluating the importance and fit of the swapped residues. While we prove that it is NP-hard to choose an optimal set of fragments under such a potential score, we develop an integer programming approach, which we call Swagmer, that works very well in practice. We demonstrate the effectiveness of our method in three swapping problems: selective recombination between beta-lactamases, activity swapping between glutathione transferases, and activity swapping between carboxylases and mutases in the purE family. We show that the selective recombination approach generates better plan (in terms of resulting potential score) than traditional site-directed recombination approaches. We also show that in all cases the optimized experiments are significantly better than ones that would result from stochastic methods.


Dental management of patients with epidermolysis bullosa.
Epidermolysis Bullosa (EB) is a group of rare, genetic skin disorders characterized by fragility and blistering to minimal trauma. All oral surfaces may be involved, including the tongue, buccal mucosa, palate, floor of the mouth and gingiva. Common oral findings of the disease include microstomia, intraoral ulcerations and bullae formation, ankyloglossia, tongue atrophy, elimination of buccal and vestibular sulci, lingual depapillation and atrophy of the palatal folds. In these case reports; systemic findings, oral manifestations and preventive measures are described for 3 patients with EB, all of whom required extensive oral management. Early dental management and preventive care to minimize caries development and improve oral health is very important for patients with EB. Pediatric dentists play an especially important role in early intervention. In describing the dental management of three EB cases, this article stresses the importance of an aggressive dental preventive programme with strict oral hygiene instructions for patients and parents along with frequent professional cleaning and fluoride therapy.


Acute microvascular action of vascular endothelial growth factor in skeletal muscle ischemia/reperfusion injury.
The purpose of this study was to investigate the acute action of vascular endothelial growth factor (VEGF) in the microcirculation of skeletal muscle subject to ischemia/reperfusion in vivo and to determine the role of nitric oxide synthase in VEGF-induced microvascular protection. A vascular pedicle isolated rat cremaster muscle model coupled with local intraarterial infusion technique was used. Each muscle underwent 4 hours of zero-flow warm ischemia followed by 2 hours of reperfusion. Femoral artery cannulation was performed before reperfusion. The infusate was administered by continuous infusion into the arterial tree of the muscle beginning at 1 minute before reperfusion and at the rate of 0.1 ml/hour throughout the entire reperfusion period. Three groups were designed: (1) the ischemia/reperfusion group, with infusion normal saline; (2) the VEGF plus ische-mia/reperfusion group, with infusion of recombinant human VEGF165 protein; and (3) the L-NA plus VEGF plus ischemia/reperfusion group, with infusion of N-nitro-L-arginine (L-NA; a nonselective nitric oxide synthase antagonist) mixed with VEGF165 protein. After 2 hours of reperfusion, microcirculation measurements including arteriole diameter, capillary perfusion, and endothelium-dependent and endothelium-independent vasodilatation were performed. The muscle was harvested and processed for reverse-transcriptase polymerase chain reaction for measuring eNOS and endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) gene expression. Reperfusion caused significant microvascular alterations including vasoconstriction, poor capillary perfusion, and endothelial dysfunction in the skeletal muscle. These alterations were significantly attenuated by intraarterial infusion of VEGF during reperfusion, but the beneficial effect of VEGF was reduced significantly by coadministration of L-NA. Reverse-transcriptase polymerase chain reaction study revealed that ischemia/reperfusion depressed eNOS mRNA expression but enhanced iNOS mRNA expression. Intraarterial infusion of VEGF during reperfusion amplified mRNA expression of eNOS but not of iNOS. Local intraarterial infusion of VEGF produced significant microvascular protection from skeletal muscle ischemia/reperfusion injury. The VEGF-induced enhancement of eNOS may play an important mechanistic role.


Aggressive angiomyxoma presenting as an ischiorectal fossa tumour.
This is a case of a young healthy woman who presented with left groin pain. On work-up, she was found to have a large, well-defined mass in the ischiorectal fossa with a percutaneous biopsy of only a benign mesenchymal mass. A multidisciplinary team of surgeons (ie, colorectal, orthopaedic, vascular and urological surgery) collaborated in planning and performing the extirpation of the tumour. Final histopathology identified the tumour to be an aggressive angiomyxoma, a benign tumour with a high predilection for local recurrence. The patient had an uneventful postoperative course, with maintenance of good functional status.


Expression of glucose transporter GLUT-1 and estrogen receptors ER-alpha and ER-beta in human breast cancer.
We attempted to describe a GLUT-1 expression in breast cancer and characterize correlation between GLUT-1 and ERs alpha and beta expression as well as correlate this with clinicopathologic features. Sixty-nine patients were involved in the study. GLUT-1, ER-alpha and ER-beta immunocytochemistry was performed using the streptavidin- biotin method. Thirty-seven (53.6%) out of total 69 were GLUT-1 positive. Of GLUT- 1 positive 45.3% were ER-alpha-positive, whereas 81.3% of ER-alpha-negative were GLUT-1 positive. Statistically significant correlation was observed between GLUT-1 and ER-alpha expression status but neither between GLUT-1 and ER-beta nor with clinicopathologic features. No statistically significant correlation was found between expression level (expressed as immunocytoreactive score) of GLUT-1, ER-alpha and ER-beta. Since most of ER-alpha-negative (81.3%) were GLUT-1 positive and significant correlation exists between the two receptors it is reasonable to assume that some functional relation might exists between the expression of two receptors.


Phototoxic properties of quinine and quinidine: two quinoline methanol isomers.
Clinical photoreactions have been reported for quinine and quinidine after systemic and topical administration. We have investigated the phototoxic properties of these two quinoline methanol isomers in vitro using the Candida albicans inhibition test and photohemolysis, and in vivo with the mouse tail phototoxicity test. Both isomers were phototoxic in the hemolysis model, quinine being the more potent compound. In the Candida test only quinidine was phototoxically active. In the mouse tail model, measuring edema, the phototoxic activity of quinidine was comparatively low, causing a 7.3% wet weight increase of tail tissue at a dose of 150 mg/kg intraperitoneally of drug and 54 J/cm2 of UVA. In spite of its structural similarity to quinidine, quinine was not phototoxic in the mouse. These studies support the assumption, based on clinical data, that quinine photoreactions probably have a non-phototoxic mechanism. For quinidine, however, light-induced reactions based on phototoxicity can not be ruled out, since low-grade phototoxic properties were demonstrated in vivo.


Predicting Regioselectivity in Radical C-H Functionalization of Heterocycles through Machine Learning.
Radical C-H bond functionalization provides a versatile approach for elaborating heterocyclic compounds. The synthetic design of this transformation relies heavily on the knowledge of regioselectivity, while a quantified and efficient regioselectivity prediction approach is still elusive. Herein, we report the feasibility of using a machine learning model to predict the transition state barrier from the computed properties of isolated reactants. This enables rapid and reliable regioselectivity prediction for radical C-H bond functionalization of heterocycles. The Random Forest model with physical organic features achieved 94.2 % site accuracy and 89.9 % selectivity accuracy in the out-of-sample test set. The prediction performance was further validated by comparing the machine learning results with additional substituents, heteroarene scaffolds and experimental observations. This work revealed that the combination of mechanism-based computational statistics and machine learning model can serve as a useful strategy for selectivity prediction of organic transformations.


Intercellular adhesion molecule 1 gene polymorphisms in Graves' disease.
It was recently suggested that genetic factors could play a major role in the development of Graves' disease (GD). The aim of the present study was to evaluate the frequency of the c.721G-->A polymorphism and the c.1405A-->G polymorphism of the intercellular adhesion molecule 1 (ICAM-1) gene in subjects with GD compared with that in healthy controls, because ICAM-1 was found to play a key role in lymphocyte infiltration into the thyroid gland and the concentration of the soluble form of ICAM-1 correlates significantly with the clinical activity and treatment status in GD. We have analyzed the association of ICAM-1 polymorphisms with the age at onset of GD and the presence of ophthalmopathy. In a group of 235 patients with GD and 211 healthy controls we have shown that polymorphism at position c.721G-->A is associated with an earlier age of GD onset and that the c.1405A-->G polymorphism of the ICAM-1 gene could predispose to Graves' ophthalmopathy. This suggests that G241R and K469E amino acid substitutions in the ICAM-1 molecule could influence the intensity/duration of the autoimmunity process and the infiltration of orbital tissues. It could be speculated that therapy that modulates ICAM-1 function may delay the onset and/or prolong the remission and/or have an influence on clinical manifestations of GD.


Differences in mental health consultation between male and female workers in the health care center of a private enterprise.
This study attempted to clarify gender differences associated with mental health consultations at a health care center (X center) that services 40,638 (34,491 men and 6,147 women) workers and is operated by a Japanese company. Data from 940 subjects (790 men and 150 women) undergoing first-time consultation at the X center between April 1996 and March 2001 were collected from the database. After matching age (within 3 years) and occupation between the male and female groups by pairing, 58 men and 58 women were compared. There was no difference in work inefficiency and diagnosis between the two groups, but the referral route of the first consultation differed significantly: males were more frequently self-referred. Fewer female than male patients were found to have work-related complaints. With regard to these work-related complaints, inadequate relationships, and especially conflicts with superiors, were found to be the most frequent cause among patients of both genders, although differences in the content of these complaints did exist.


Chemical, Thermal and Spectroscopic Methods to Assess Biodegradation of Winery-Distillery Wastes during Composting.
The objective of this work was to study the co-composting process of wastes from the winery and distillery industry with animal manures, using the classical chemical methods traditionally used in composting studies together with advanced instrumental methods (thermal analysis, FT-IR and CPMAS 13C NMR techniques), to evaluate the development of the process and the quality of the end-products obtained. For this, three piles were elaborated by the turning composting system, using as raw materials winery-distillery wastes (grape marc and exhausted grape marc) and animal manures (cattle manure and poultry manure). The classical analytical methods showed a suitable development of the process in all the piles, but these techniques were ineffective to study the humification process during the composting of this type of materials. However, their combination with the advanced instrumental techniques clearly provided more information regarding the turnover of the organic matter pools during the composting process of these materials. Thermal analysis allowed to estimate the degradability of the remaining material and to assess qualitatively the rate of OM stabilization and recalcitrant C in the compost samples, based on the energy required to achieve the same mass losses. FT-IR spectra mainly showed variations between piles and time of sampling in the bands associated to complex organic compounds (mainly at 1420 and 1540 cm-1) and to nitrate and inorganic components (at 875 and 1384 cm-1, respectively), indicating composted material stability and maturity; while CPMAS 13C NMR provided semi-quantitatively partition of C compounds and structures during the process, being especially interesting their variation to evaluate the biotransformation of each C pool, especially in the comparison of recalcitrant C vs labile C pools, such as Alkyl /O-Alkyl ratio.


Breast Density Knowledge in a Screening Mammography Population Exposed to Density Notification.
Women are increasingly informed about their breast density due to state density reporting laws. However, accuracy of personal breast density knowledge remains unclear. We compared self-reported with clinically assessed breast density and assessed knowledge of density implications and feelings about future screening. From December 2017 to January 2020, we surveyed women aged 40 to 74 years without prior breast cancer, with a normal screening mammogram in the prior year, and ≥1 recorded breast density measures in four Breast Cancer Surveillance Consortium registries with density reporting laws. We measured agreement between self-reported and BI-RADS breast density categorized as "ever-dense" if heterogeneously or extremely dense within the past 5 years or "never-dense" otherwise, knowledge of dense breast implications, and feelings about future screening. Survey participation was 28% (1,528 of 5,408), and 59% (896 of 1,528) of participants had ever-dense breasts. Concordance between self-report versus clinical density was 76% (677 of 896) among women with ever-dense breasts and 14% (89 of 632) among women with never-dense breasts, and 34% (217 of 632) with never-dense breasts reported being told they had dense breasts. Desire for supplemental screening was more frequent among those who reported having dense breasts 29% (256 of 893) or asked to imagine having dense breasts 30% (152 of 513) versus those reporting nondense breasts 15% (15 of 102) (P = .003, P = .002, respectively). Women with never-dense breasts had 6.3-fold higher odds (95% confidence interval:3.39-11.80) of accurate knowledge in states reporting density to all compared to states reporting only to women with dense breasts. Standardized communications of breast density results to all women may increase density knowledge and are needed to support informed screening decisions.


RelB-dependent stromal cells promote T-cell leukemogenesis.
The Rel/NF-kappaB transcription factors are often activated in solid or hematological malignancies. In most cases, NF-kappaB activation is found in malignant cells and results from activation of the canonical NF-kappaB pathway, leading to RelA and/or c-Rel activation. Recently, NF-kappaB activity in inflammatory cells infiltrating solid tumors has been shown to contribute to solid tumor initiation and progression. Noncanonical NF-kappaB activation, which leads to RelB activation, has also been reported in breast carcinoma, prostate cancer, and lymphoid leukemia. Here we report a novel role for RelB in stromal cells that promote T-cell leukemogenesis. RelB deficiency delayed leukemia onset in the TEL-JAK2 transgenic mouse model of human T acute lymphoblastic leukemia. Bone marrow chimeric mouse experiments showed that RelB is not required in the hematopoietic compartment. In contrast, RelB plays a role in radio-resistant stromal cells to accelerate leukemia onset and increase disease severity. The present results are the first to uncover a role for RelB in the crosstalk between non-hematopoietic stromal cells and leukemic cells. Thus, besides its previously reported role intrinsic to specific cancer cells, the noncanonical NF-kappaB pathway may also play a pro-oncogenic role in cancer microenvironmental cells.


Localized breathing modes in granular crystals with defects.
We study localized modes in uniform one-dimensional chains of tightly packed and uniaxially compressed elastic beads in the presence of one or two light-mass impurities. For chains composed of beads of the same type, the intrinsic nonlinearity, which is caused by the Hertzian interaction of the beads, appears not to support localized, breathing modes. Consequently, the inclusion of light-mass impurities is crucial for their appearance. By analyzing the problem's linear limit, we identify the system's eigenfrequencies and the linear defect modes. Using continuation techniques, we find the solutions that bifurcate from their linear counterparts and study their linear stability in detail. We observe that the nonlinearity leads to a frequency dependence in the amplitude of the oscillations, a static mutual displacement of the parts of the chain separated by a defect, and for chains with two defects that are not in contact, it induces symmetry-breaking bifurcations.


Non-vitamin K antagonist oral anticoagulants in adults with a Fontan circulation: are they safe.
In Fontan patients with atrial arrhythmias (AA), non-vitamin K antagonist oral anticoagulants(NOACs) have a class III recommendation according to the Pediatric & Congenital Electrophysiology Society (PACES)/Heart Rhythm Society (HRS) guideline in 2014, due to lack of data on outcomes as opposed to evidence of harm. To address this gap in data, we investigated the safety and efficacy of NOACs in adults with a Fontan circulation in a worldwide study. This is an international multicentre prospective cohort study, using data from the NOTE (non-vitamin K antagonist oral anticoagulants for thromboembolic prevention in patients with congenital heart disease) registry. The study population comprised consecutive adults with a Fontan circulation using NOACs. Follow-up took place at 6 months and yearly thereafter. The primary endpoints were thromboembolism and major bleeding. Secondary endpoint was minor bleeding. From April 2014 onward, 74 patients (mean age 32±10 years (range 18-68), 54% male) with a Fontan circulation using NOACs were included. During a median follow-up of 1.2 (IQR 0.8-2.0) years, three thromboembolic events (2.9 per 100 patient-years (95% CI 0.7 to 7.6)) and three major bleedings (2.9 per 100 patient-years (95% CI 0.7 to 7.6)) occurred in five atriopulmonary Fontan and one total cavopulmonary connection Fontan patients with AA. Fifteen patients experienced minor bleeding episodes (15.8 per 100 patient-years (95% CI 9.1 to 25.2)). In patients (n=37) using vitamin K antagonists (VKAs) prior to the initiation of NOAC, annual incidence of historical thromboembolic events and major bleeding were 2.4% (95% CI 0.4% to 7.4%) (n = 2) and 1.2% (95% CI 0.7% to 5.1%) (n = 1), respectively. In this review of the largest Fontan cohort using NOACs with prospective follow-up, NOACs appear to be well tolerated and their efficacy and safety during short-term follow-up seem comparable to VKAs. Longer term data are required to confirm these promising short-term results.


The effects of psychological factors on recovery from surgery.
This paper has reviewed correlational studies from both inpatient hospital settings and outpatient oral surgery that demonstrate that several psychological factors are related to postsurgical recovery. Examination of these factors indicates that dentists might improve patients' recovery by giving the surgery a more positive meaning (making the outcome seem desirable), improving patients' acceptance of their condition, making patients' expectations more positive and, reducing anxiety about recovery. Other psychological factors may be helpful in identifying patients who need more support, for example, those with higher trait anxiety, vigilant coping behavior, or an internal locus of control. The review of intervention studies indicates that the best preparation techniques include giving positive suggestions and teaching coping techniques. The value of giving increased amounts of information has not been demonstrated. Also, the literature is not conclusive on varying the type of preparation to fit the personality traits of patients.


Retrieving GPCR data from public databases.
Improvements in databases have already impacted GPCR research. The purpose of the review is to give a snapshot of the GPCR data available and provide utility examples. Consequently, this review covers a small set of major databases, including UniProt for proteins, Ensembl for genes, ChEMBL for bioactive chemistry and SureChEMBL for patents. In addition, two portals are outlined, GPCRdb and the IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb) that are based on expert annotation. The former has an emphasis on structures, sequences, point mutations, analysis tools and visualisation. The latter focuses on endogenous GPCR ligands, pharmacological modulation, approved drugs, clinical candidates and tool compounds. Since data growth is accelerating, those embarking on GPCR projects should not only check databases but also recent journal and patent publications.


Association of Health Care Utilization With Rates of Perforated Appendicitis in Children 18 Years or Younger.
The pediatric perforated appendix rate is a quality metric measured by the Agency for Healthcare Research and Quality (AHRQ) that reflects access to care. The association of health care utilization prior to presentation with appendicitis is unknown. To determine whether increased health care utilization prior to presentation with appendicitis is associated with lower perforated appendicitis rates in children. Retrospective cohort study of privately insured children drawn from large employer and insurance company administrative data found in the Truven MarketScan national insurance claims database. Cases of appendicitis were identified among 38 348 children 18 years or younger from January 1, 2010, through December 31, 2013, with corresponding primary health care encounters from January 1, 2009, through December 31, 2012. In all, 19 109 eligible children were identified using International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes for appendicitis after excluding those patients who did not have continuous insurance coverage during the study period. Statistical analysis was performed from September 1, 2016, to October 15, 2017. Health care utilization was determined by the number of outpatient clinic encounters for each patient in the 1 to 12 months before presentation with appendicitis. Perforated appendicitis was defined according to the AHRQ by using ICD-9 codes for perforation and hospital length of stay of 3 or more days. Logistic regression models were used for perforated appendicitis after adjustment for age, sex, income, gastrointestinal comorbidities, geographic region, and insurance type. We identified 38 348 children 18 years or younger with ICD-9 diagnosis codes for appendicitis, and 19 109 children remained for analysis after applying exclusion criteria. Of these, 11 422 were boys (59.8%); the mean (SD) age was 12.4 (3.9) years. Of the 19 109 children identified who underwent appendectomy, 5509 (28.8%) presented with perforated appendicitis. Children with perforation had lower outpatient health care utilization in the year before presentation compared with those diagnosed with acute appendicitis (4554 of 5509 children [82.7%] vs 11 937 of 13 600 [87.8%]; P < .001). In the adjusted model, outpatient health care utilization before presentation was associated with lower odds of perforated appendicitis (odds ratio [OR], 0.63; 95% CI, 0.58-0.69; P < .001). This association increased with visit frequency in the year before presentation (OR, 0.86; 95% CI, 0.77-0.95 for 1-2 visits, P = .003; OR, 0.61; 95% CI, 0.55-0.67 for 3-6 visits, P < .001; and OR, 0.43; 95% CI, 0.38-0.48 for ≥7 visits [5-18 years], P < .001). Covariates associated with perforation included younger age, geographic region, family income, and higher out-of-pocket insurance plans. Among insured children 18 years or younger, increased health care utilization was associated with lower rates of perforated appendicitis. Primary health care relationships may facilitate timely presentation or serve as a marker for health-related self-efficacy, thereby contributing to outcomes for acute surgical conditions.


Reasons for and perceived benefits of utilizing complementary and alternative medicine in U.S. adults with migraines/severe headaches.
We estimated prevalence rates of complementary and alternative medicine (CAM) use by reason for use (treatment, wellness, or both), and examined perceived benefits of using CAM among U.S. adults with migraines/severe headaches. The 2012 National Health Interview Survey, which represents non-institutionalized adults with migraines/severe headaches (n = 4447 unweighted), were used. Of the study sample, 41.3% used some form of CAM in the past year. Nearly a third of them (29.6%) used CAM for wellness only and 59% used CAM for both wellness and treatment. In given six self-reported perceived benefits, those who used CAM for wellness only and for a combination of both treatment and wellness had higher likelihoods of reporting benefits for all categories (p < 0.05), except for better sleep, when compared to those who used CAM for treatment only. CAM use was associated with an improvement in several health-related quality of life outcomes in U.S. adults with migraines/severe headaches.


[Immediate plastic reconstruction following tumor removal in the area of the head and neck].
Primary reconstruction after tumour resection in the head and neck region is indicated to cover vital structures such as the eye, the nasal and oral cavities, nerves, blood vessels and skeleton for optimum reconstruction of functions and appearance. Local, regional and free flaps are applied. The special topographic requirements are illustrated with clinical cases.


Comparison of chemotherapy plus bevacizumab vs. chemotherapy alone as third-line treatment or beyond for advanced non-small cell lung cancer: A propensity score-matched analysis.
The addition of bevacizumab to chemotherapy has demonstrated efficacy as a first-line treatment for non-small cell lung cancer (NSCLC). Whether this combination is effective as a salvage treatment for patients with NSCLC remains unclear. The present retrospective study was designed to compare the efficacy and safety of chemotherapy plus bevacizumab with chemotherapy alone as a third-line, or continuing, treatment for patients with NSCLC. Between January 2011 and June 2016, a total of 38 patients with stage IV NSCLC who had received chemotherapy plus bevacizumab subsequent to failure of ≥2 prior regimens were matched with 38 patients who had received chemotherapy alone using propensity score matching from a dataset of 165 patients. The variables that were analyzed included age, sex, smoking history, histology, epithelial growth factor receptor mutation status, number of prior regimens and type of chemotherapy regimen. Univariate and multivariate analyses were used to evaluate the prognostic factors for survival outcomes and tumor response, and toxicity analyses were performed. The objective response rate (ORR) and disease control rate (DCR) were improved in patients who underwent chemotherapy-bevacizumab treatment compared with chemotherapy alone (ORR, 23.7 vs. 5.3%, P<0.001; DCR, 65.8 vs. 31.6%, P<0.001). Progression-free survival was prolonged in the chemotherapy-bevacizumab group compared with the chemotherapy-alone group (median, 3.9 vs. 2.2 months; HR, 0.54; 95% CI, 0.32-0.89, P=0.014). Incidence of ≥grade 3 adverse events was low and similar across the groups. The combination of chemotherapy and bevacizumab is a potentially effective and safe alternative salvage treatment for patients with NSCLC who have not received bevacizumab treatment previously.


Isolation of genomic sequence encoding a biologically active bovine TGF-alpha protein.
Genomic clones encoding bovine TGF-alpha were identified by hybridization with probes derived from human TGF-alpha sequence. Nucleotide sequence of the clones predicts that mature bovine TGF-alpha is a 50 amino acid polypeptide which shares 96% and 92% homology with human and rat TGF-alpha, respectively. Bovine TGF-alpha with the predicted sequence was chemically synthesized and tested for activity. Synthetic bovine TGF-alpha competes in a radioreceptor assay with labelled mouse EGF with activity parallel to that of human TGF-alpha and mouse EGF. The mitogenic activity of bovine TGF-alpha is comparable to that of human EGF in causing proliferation of bovine mammary epithelial cells. An approximately 5.0 kilobase RNA transcript is observed in polyadenylated RNA from MDBK cells by Northern blot analysis. The polymerase chain reaction detects the presence of a TGF-alpha transcript in many bovine tissues. These data indicate that bovine TGF-alpha may be a normal regulator of cell growth in the bovine animal.


Oxidation-initiated Nazarov cyclization of vinyl alkoxyallenes.
A mild method for the diastereoselective formation of C(4), C(5)-disubstituted cyclopentenones has been developed, involving formation of a pentadienyl cation via diastereoselective oxidation of a vinyl alkoxyallene. Conrotatory electrocyclization provides the cyclopentenone product. The broad scope, mild conditions, and uncommon substitution pattern accessible through this transformation make it a useful addition to the existing repertoire of cyclopentenone synthetic methods.


Solar-Driven Catalytic Urea Oxidation for Environmental Remediation and Energy Recovery.
Invited for this month's cover is the group of Chong Peng at the Shanghai Jiao Tong University. The image shows how the solar-driven catalytic urea conversion interconnects with the sustainable development of energy and environment. The Review itself is available at 10.1002/cssc.202201263.


Use of the internet to optimise collaborative healthcare research.
This article explores some of the issues related to setting up and maintaining virtual collaborations in healthcare research. Using the learning from one such collaboration--the Virtual Institute of Research in Healthcare Practice--and the literature on collaborative and virtual working, this article examines the interface of collaboration and virtual working and some of the methods that may maximise achievement. Some pointers are also offered for those setting up or working in the area of collaborative healthcare research.


Sustainability, survivability, and the paradox of New Orleans.
Some precepts of the urban sustainability movement derive from the premise that economic expansion, population growth, and physical sprawl lead to a decline in quality of life, ecological damage, and eventual unsustainability. But what about cities that are failing-losing population, losing investment, losing infrastructure, even losing land? This article challenges conventional sustainability concepts, usually derived from the experiences of ascending cities, with the notion of survivability that confronts declining cities. Should troubled cities, such as New Orleans, located on the eroding Gulf of Mexico coastal region of the state of Louisiana, be held to different sustainability standards? Could urban expansion, in some cases, actually stem environmental degradation and enhance survivability?


Nitric oxide scavenging, alone or with nitric oxide synthesis inhibition, modulates vascular hyporeactivity in rats with intraperitoneal sepsis.
Elevated levels of nitric oxide (NO) may be a primary cause of the vascular hyporeactivity (vasoplesia) and refractory hypotension in sepsis. This study was initiated to determine the efficacy of NO scavenging with acellular hemoglobin (Hb) solution in modulating sepsis-mediated vasoplesia. Male Sprague Dawley rats were subjected to sepsis by cecal ligation and puncture (CLP). Twenty-four hours post-CLP, the animals were randomly assigned to one of four groups (n = 5-6 each) and given an intravenous injection of 0.5 mL bovine serum albumin (BSA; 5 g/dL), 0.5 mL human Hb (7g/dL), 50 microL Nomega-nitro L-arginine methyl ester (NAME; 1 M), or both Hb and NAME. Blood pressure (BP), cardiac output, systemic vascular resistance, and vascular reactivity (VR) to norepinephrine (NE; 40 ng/Kg) were assessed before and after an experimental treatment. In some animals, inducible NO synthase (iNOS) mRNA expression was assessed in selected tissue samples harvested at the conclusion of experiment using a reverse transcription-polymerase chain reaction (RT-PCR) method. Treatment with Hb, NAME, or NAME + Hb elicited a significant improvement in mean BP and VR compared with the control (BSA) group (P < 0.05, analysis of variance and Neuman-Keuls tests). Tissue samples from 24-h CLP rats clearly exhibited iNOS gene expression; higher iNOS gene expression in the intestine compared with aorta suggests that the intestine may be a major source of the elevated NO level in this model. In conclusion, NO scavenging with Hb, alone, or in combination with NO synthesis inhibition, appears to be effective in modulating sepsis-mediated vascular hyporeactivity and may reduce complications associated with global NO synthesis inhibition.


Validity of inorganic nanosheets as an efficient planar substituent to enhance the enantioselectivity of transition-metal-catalyzed asymmetric synthesis.
Effectively enhancing the enantioselectivity is a persistent challenge in heterogeneous asymmetric catalysis. Here, the validity of a layered double hydroxides (LDH) nanosheet as an efficient planar substituent to enhance the enantioselectivity has been investigated theoretically; first in vanadium-catalyzed asymmetric epoxidation of allylic alcohols, and then in zinc-catalyzed direct asymmetric aldol addition. The computational predication is further confirmed experimentally in zinc-catalyzed direct asymmetric aldol addition by controlling the location of catalytic sites.


Performance characteristics of rheumatoid factor and anti-cyclic citrullinated peptide antibody assays may impact ACR/EULAR classification of rheumatoid arthritis.
Rheumatoid factor (RF) and anti-cyclic citrullinated protein/peptide antibodies (ACPA) are integrated in the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for rheumatoid arthritis (RA). The objectives of this study were to evaluate the technical and diagnostic performance of different RF and ACPA assays and to evaluate whether differences in performance impact RA classification. Samples from 594 consecutive patients who for the first time consulted a rheumatologist (44 of whom were diagnosed with RA) and 26 extra newly diagnosed patients with RA were analysed with six different RF assays (Menarini, Thermo Fisher, Inova, Roche, Abbott, Euroimmun) and seven different ACPA assays (Menarini, Thermo Fisher, Inova, Roche, Abbott, Euro Diagnostica, Euroimmun). We found differences in analytical performance between assays. There was poor numerical agreement between the different RF and ACPA assays. For all assays, the likelihood ratio for RA increased with increasing antibody levels. The areas under the curve of receiver operating characteristic analysis of the RF (range 0.676-0.709) and ACPA assays (range 0.672-0.769) only differed between some ACPA assays. Nevertheless, using the cut-off proposed by the manufacturer, there was a large variation in sensitivity and specificity between assays (mainly for RF). Consequently, depending on the assay used, a subgroup of patients (13% for RF, 1% for ACPA and 9% for RF/ACPA) might or might not be classified as RA according to the 2010 ACR/EULAR criteria. Due to poor harmonisation of RF and ACPA assays and of test result interpretation, RA classification according to 2010 ACR/EULAR criteria may vary when different assays are used.


Impact of Sweet Potato Starch-Based Nanocomposite Films Activated With Thyme Essential Oil on the Shelf-Life of Baby Spinach Leaves.
Salmonella Typhimurium (S. Typhi) and Escherichia coli (E. coli) have been responsible for an increasing number of outbreaks linked to fresh produce, such as baby spinach leaves, in the last two decades. More recently, antimicrobial biodegradable packaging systems have been attracting much attention in the food packaging industry as eco-friendly alternatives to conventional plastic packaging. The objective of this study was to evaluate the effect of antibacterial nanocomposite films on inoculated spinach leaves and on the sensory properties of these leaves during eight days of refrigerated storage. In this study, an antibacterial film comprised of sweet potato starch (SPS), montmorillonite (MMT) nanoclays and thyme essential oil (TEO) as a natural antimicrobial agent was developed. Our results showed that the incorporation of TEO in the film significantly (p < 0.05) reduced the population of E. coli and S. Typhi on fresh baby spinach leaves to below detectable levels within five days, whereas the control samples without essential oil maintained approximately 4.5 Log colony forming unit (CFU)/g. The sensory scores for spinach samples wrapped in films containing TEO were higher than those of the control. This study thus suggests that TEO has the potential to be directly incorporated into a SPS film to prepare antimicrobial nanocomposite films for food packaging applications.


Homozygous protein C deficiency: description of a new mutation and successful treatment with low molecular weight heparin.
We present a kindred with a new mutation of the protein C gene, in which the proband had an unusual clinical presentation. The relationship between warfarin induced skin necrosis and level of anticoagulation was investigated. The pharmacokinetics of protein C concentrate was assessed to determine frequency of replacement therapy. The clinical and biochemical efficacy of therapy with low molecular weight heparin (LMWH) was assessed. The effect of long-term LMWH on bone density in the growing child was monitored using whole body densitometry. Warfarin therapy required an INR of greater than 3.5 to avoid skin necrosis. If protein C replacement was to be used, doses of 100 U/kg/day would have been required to maintain protein C levels consistently at or above 0.20 U/ml. While receiving prophylactic therapy with LMWH for almost 3 years, there were no episodes of recurrent thrombosis, no skin necrosis and no bleeding. Biochemical markers of in vivo thrombin generation were suppressed and within the normal range. Bone density continued to increase at the normal rate throughout the treatment period. LMWH is an effective form of long-term therapy for homozygous protein C deficient patients with measurable protein C levels.


Influence of Human Telomerase Reverse Transcriptase Mutation on the Aggressiveness and Recurrence in Meningiomas.
Over 200 human telomerase reverse transcriptase (hTERT) polymorphism combinations have been implicated in the development of cancer. This study aimed to evaluate hTERT mutations in meningioma tissue and its association with meningioma. A total of 90 patients who underwent surgery between 2006 and 2015 and were histopathologically diagnosed with meningioma (WHO 2016) were included. Among the 90 participants included herein, 50 (55.5%) and 40 (44.5%) were female and male, respectively, with an average age of 56.2 ± 14 years. Mean Ki-67 values were 10.56% (SD 12.41, range 0-60), while the mean follow-up duration was 39.1 months (SD 26.3). Low- and high-grade patients had a mean Ki-67 score of 4.31% (SD 3.58, range 0-16) and 19.92% (SD 14.91, range 2-60) (p = 0.0001). Our results showed a moderate positive correlation between Ki-67 score and the presence of hTERT mutation (Pearson correlation test, r = 0.5161; p = 0.0001). Patients with an hTERT mutation > 30% had significantly higher risk for reoperation than those with lower levels of mutation (p = 0.016, chi square test). None of the patients requiring reoperation had an hTERT mutation < 10%. Moreover, high-grade patients had a 7.2 times higher risk of reoperation than those with an hTERT mutation > 30%. The presence of hTERT mutation, in addition to high Ki-67, indicated a more aggressive meningioma disease course and potentially increased risk of recurrence.


Signal changes in the spinal cord of the rat after injection of formalin into the hindpaw: characterization using functional magnetic resonance imaging.
Changes in metabolism and local circulation occur in the spinal cord during peripheral noxious stimulation. Evidence is presented that this stimulation also causes signal intensity alterations in functional magnetic resonance images of the spinal cord during formalin-induced pain. These results indicate the potential of functional magnetic resonance imaging in assessing noninvasively the extent and intensity of spinal cord excitation in this well characterized pain model. Therefore, the aim of this study was to establish functional magnetic resonance imaging as a noninvasive method to characterize temporal changes in the spinal cord after a single injection of 50 microl of formalin subcutaneously into the hindpaw of the anesthetized rat. This challenge produced a biphasic licking activity in the freely moving conscious animal. Images of the spinal cord were acquired within 2 min, enabling monitoring of the site and the temporal evolution of the signal changes during the development of formalin-induced hyperalgesia without the need of any surgical procedure. The time course of changes in the spinal cord functional image in the isoflurane-anesthetized animal was similar to that obtained from behavioral experiments. Also, comparable physiological data, control experiments, and the inhibition of a response through application of the local anesthetic agent lidocaine indicate that the signal changes observed after formalin injection were specifically related to excitability changes in the relevant segments of the lumbar spinal cord. This approach could be useful to characterize different models of pain and hyperalgesia and, more importantly, to evaluate effects of analgesic drugs.


[Urachal adenocarcinoma: analysis of 3 cases].
Adenocarcinoma of the urachus is a very rare disease. It often remains undiagnosed for a long time and has an aggressive course. Surgery, the only potentially curative treatment, was initially very extensive, but this attitude has been revised more recently. The authors present three clinical cases, and discuss the treatment options. The first two cases were treated by one-stage resection and the third case, which presented with a mucus collection in the abdomen with "signet ring" cells, was treated by Intraperitoneal ChemoHyperthermia (IPCH) during second-look laparotomy. A review of the literature shows that the current tendency is towards less mutilating surgery. Diagnostic examinations, allowing earlier detection of this disease, may possibly alter its prognosis, which was considered to be very poor up until recently.


Aortitis is an under-recognized manifestation of antiphospholipid syndrome: A case report and literature review.
Aortitis is a classic manifestation of large vessel vasculitis. Antiphospholipid syndrome (APS), sometimes known as Hughes syndrome, is an acquired autoimmune disorder that manifests clinically as recurrent venous or arterial thrombosis. Patients with APS may also suffer from various underlying diseases, most frequently systemic lupus erythematosus (SLE). Catastrophic antiphospholipid syndrome (CAPS) is a rare but serious complication of APS characterized by failure of several organs due to diffuse microcirculatory thrombi. Its main manifestations involve the kidneys, lungs, heart and central nervous system, and require early diagnosis and rapid therapeutic management. While APS can affect virtually any blood vessel, aortitis is not a known symptom of APS. We report the case of a 36-year-old patient with APS and SLE who presented with CAPS during pregnancy, with no concomitant SLE flare. The first manifestation of CAPS was aortitis, preceding renal, cardiac and haematological manifestations. The outcome was favourable with combined treatment including corticosteroids, anticoagulants, plasma exchange and rituximab. We then carried out a literature search for papers describing the presence of aortitis in APS and/or SLE. In the cases of aortic involvement identified in the literature, including another case of CAPS, the occurrence of aortitis in SLE, often associated with the presence of antiphospholipid antibodies/APS, suggests that aortitis should be considered as an under-recognized manifestation and potential non-criterion feature of APS.


Accuracy of sonographic estimated fetal weight in suspected macrosomia: the likelihood of overestimating and underestimating the true birthweight.
Objective: Macrosomia has increased risk of serious adverse outcomes for both infants and their mothers. As such, many providers recommend induction of labor or cesarean delivery (CD) based on sonographic estimated fetal weight (sonoEFW) cutoffs. It is known that sonoEFW is a poor predictor of birthweight (BW), especially at the extremes of weight. It is not clear, however, whether sonoEFWs tend to underestimate or overestimate the true BW among fetuses with suspected macrosomia. The objective of this study was to compare rates of overestimation of BW among women with suspected macrosomia by sonoEFW.Methods: This was a retrospective cohort study of women who presented to a single maternal-fetal medicine ultrasound unit within 2 weeks prior to delivery from January 2011 to November 2017. We identified women who received a sonoEFW ≥4000 g. The study sample was divided into four sonoEFW categories: 4000-4249, 4250-4499, 4500-4749, and ≥4750 g. Accuracy of sonoEFW was compared across groups, with the primary outcome being overestimation of BW.Results: A total of 502 patients were included, of whom 301 (60.1%) had a sonoEFW 4000-4249 g, 135 (26.9%) had a sonoEFW 4250-4499 g, 45 (9.0%) had a sonoEFW 4500-4749 g, and 21 (4.2%) had a sonoEFW ≥4750 g. In each sonoEFW group, the risk of overestimating BW was greater than 50%, and the likelihood of overestimation of BW increased significantly across sonoEFW groups (69.4, 76.3, 80.0, 95.2%, p < .001). This held true after adjusting for differences in baseline characteristics, including diabetes and amniotic fluid index. BW ≥4500 g was not accurately predicted. Among women with sonoEFW 4500-4749 g, only 28.9% delivered a neonate with a BW >4500 g; for women with a sonoEFW ≥4750 g, only 47.6% had a BW >4500 g. One hundred sixty-one (32.1%) women underwent CD for suspected macrosomia. Of these CDs, 48 (29.8%) of neonates had a BW <4000 g and 134 (83.2%) had a BW <4500 g.Conclusion: In patients undergoing sonoEFW within 2 weeks of delivery, sonoEFWs ≥4000 g are significantly more likely to overestimate than underestimate the true BW. Obstetricians should be cautious about intervening based on sonoEFW alone, given the high risk that this value is an overestimation of the true weight.


[Effects of antibiotics in the prevention of infections following vaginal and abdominal hysterectomy: an evaluation by febrile morbidity and fever index].
The current references written in English concerning effect of prophylactic antibiotics in vaginal and abdominal simple hysterectomy have been reviewed. Febrile morbidity was evaluated for antibiotic treated and untreated groups. In most studies, the definition of febrile morbidity was a temperature of 38 degrees C or greater on 2 separate occasions excluding the first 24 hours after the operation. Fever index in degree hours was also compared between 2 groups in some studies. Of 30 studies in vaginal hysterectomy reported between 1969 and 1981, 29 showed that antibiotic prophylaxis successfully decreased postoperative febrile morbidity. Of 15 studies in abdominal hysterectomy reported between 1972 and 1982, 12 showed the significant decrease of febrile morbidity in the treated group. However, pelvic infection in only 2 and wound infection in 5 were reduced. The length of hospital stay was found to be shorter for the treated group in vaginal and abdominal hysterectomy. The beneficial effect of prophylactic antibiotics in abdominal hysterectomy were less compelling than those for vaginal hysterectomy. Although recent studies indicated that a short perioperative use of antibiotics or even a single dose was effective as long-term prophylaxis, the most effective method and duration awaits further evaluation.


Enhanced removal of Cr(VI) by biochar with Fe as electron shuttles.
Biochar is extensively used as an effective soil amendment for environmental remediation. In addition to its strong contaminant sorption capability, biochar also plays an important role in chemical transformation of contaminant due to its inherent redox-active moieties. However, the transformation efficiency of inorganic contaminants is generally very limited when the direct adsorption of contaminants on biochar is inefficient. The present study demonstrates the role of Fe ion as an electron shuttle to enhance Cr(VI) reduction by biochars. Batch experiments were conducted to examine the effects of Fe(III) levels, pyrolysis temperature of biochar, initial solution pH, and biochar dosage on the efficiency of Cr(VI) removal. Results showed a significant enhancement in Cr(VI) reduction with an increase in Fe(III) concentration and a decrease of initial pH. Biochar produced at higher pyrolysis temperatures (e.g., 700°C) favored Cr(VI) removal, especially in the presence of Fe(III), while a higher biochar dosage proved unfavorable likely due to the agglomeration or precipitation of biochar. Speciation analysis of Fe and Cr elements on the surface of biochar and in the solution further confirmed the role of Fe ion as an electron shuttle between biochar and Cr(VI). The present findings provide a potential strategy for the advanced treatment of Cr(VI) at low concentrations as well as an insight into the environmental fate of Cr(VI) and other micro-pollutants in soil or aqueous compartments containing Fe and natural or engineered carbonaceous materials.


The convergence coefficient across political systems.
Formal work on the electoral model often suggests that parties or candidates should locate themselves at the electoral mean. Recent research has found no evidence of such convergence. In order to explain nonconvergence, the stochastic electoral model is extended by including estimates of electoral valence. We introduce the notion of a convergence coefficient, c. It has been shown that high values of c imply that there is a significant centrifugal tendency acting on parties. We used electoral surveys to construct a stochastic valence model of the the elections in various countries. We find that the convergence coefficient varies across elections in a country, across countries with similar regimes, and across political regimes. In some countries, the centripetal tendency leads parties to converge to the electoral mean. In others the centrifugal tendency dominates and some parties locate far from the electoral mean. In particular, for countries with proportional electoral systems, namely, Israel, Turkey, and Poland, the centrifugal tendency is very high. In the majoritarian polities of the United States and Great Britain, the centrifugal tendency is very low. In anocracies, the autocrat imposes limitations on how far from the origin the opposition parties can move.


The Interrelationship between Obesity and Race in Breast Cancer Prognosis: A Prospective Cohort Study.
Obesity is associated with an increased breast cancer risk in postmenopausal women and may contribute to worse outcomes. Black women experience higher obesity and breast cancer mortality rates than non-Black women. We examined associations between race, obesity, and clinical tumor stage with breast cancer prognosis. We conducted a prospective cohort study in 1,110 breast cancer patients, using univariable and multivariable Cox regression analyses to evaluate the effects of obesity, race/ethnicity, and clinical tumor stage on progression-free and overall survival (PFS and OS). 22% of participants were Black, 64% were Hispanic White, and 14% were non-Hispanic White or another race. 39% of participants were obese (body mass index [BMI] ≥ 30 kg/m2). In univariable analyses, tumor stage III-IV was associated with worse PFS and OS compared to tumor stage 0-II (hazard ratio [HR] = 4.68, 95% confidence interval [CI] = 3.52-6.22 for PFS and HR = 5.92, 95% CI = 4.00-8.77 for OS). Multivariable analysis revealed an association between Black race and worse PFS in obese (HR = 2.19, 95% CI = 1.06-4.51) and non-obese (HR = 2.11, 95% CI = 1.05-4.21) women with tumors staged 0-II. Obesity alone was not associated with worse PFS or OS. Results suggest a complex interrelationship between obesity and race in breast cancer prognosis. The association between Black race and worse PFS in tumor stages 0-II underscores the importance of early intervention in this group. Future studies are warranted to evaluate whether alternative measures of body composition and biomarkers are better prognostic indicators than BMI among Black breast cancer survivors.


Sesquiterpene Cyclizations inside the Hexameric Resorcinarene Capsule: Total Synthesis of δ-Selinene and Mechanistic Studies.
The synthesis of terpene natural products remains a challenging task due to the enormous structural diversity in this class of compounds. Synthetic catalysts are unable to reproduce the tail-to-head terpene cyclization of cyclase enzymes, which create this diversity from just a few simple linear terpene substrates. Recently, supramolecular structures have emerged as promising enzyme mimetics. In the present study, the hexameric resorcinarene capsule was utilized as an artificial cyclase to catalyze the cyclization of sesquiterpenes. With the cyclization reaction as the key step, the first total synthesis of the sesquiterpene natural product δ-selinene was achieved. This represents the first total synthesis of a sesquiterpene natural product that is based on the cyclization of a linear terpene precursor inside a supramolecular catalyst. To elucidate the reaction mechanism, detailed kinetic studies and kinetic isotope measurements were performed. Surprisingly, the obtained kinetic data indicated that a rate-limiting encapsulation step is operational in the cyclization of sesquiterpenes.


Clinical conference in pulmonary disease. Factors influencing upper airway closure.
The factors which produce closure of the upper airway (UAW) in patients with the sleep apnea syndrome are still poorly understood. A distinction should be made between the factors which induce closure and those which reopen the UAW. Neurologic factors include arousal phenomena, the magnitude and timing of various motor outputs, and postsynaptic inhibition. Mechanical factors include the anatomy of the UAW, especially that above the tongue, the position of the neck and jaw, and mucosal adherence once occlusion has occurred. Muscle factors include the type of myosin isozyme, the forces generated by the large number of UAW muscles and the diaphragm, and the possibility of high-frequency fatigue occurring during occlusion. Hypoxia and acidosis probably play a critical role in making the UAW less stable. Currently, the best method to prevent UAW closure is by nasal CPAP. Patients with life-threatening arrhythmias due to sleep apnea should have a tracheostomy. The role of drugs is controversial. Respiratory or muscle stimulants should probably be avoided; oxygen, medroxyprogesterone, and protriptyline may be useful adjuncts.


Comparative investigation of the effects of zardaverine and theophylline on pulmonary function in rats.
Zardaverine (Byk Gulden, Konstanz, Germany) is a new selective phosphodiesterase (PDE) III/IV inhibitor. The bronchodilating and bronchoprotective potency of zardaverine and the nonselective PDE inhibitor theophylline was compared by measuring typical spontaneous and forced respiratory function parameters in anesthetized female Wistar rats using whole-body plethysmography. Zardaverine (3, 10, 30 mumol/kg) and theophylline (30, 100, 300 mumol/kg), respectively, were given orally in 4% Methocel/0.9% saline solution 20 min before measurement. One week before treatment, control measurements were performed in the same animals after administration of the vehicle. When spontaneously breathing, the 30 mumol/kg zardaverine- (300 mumol/kg theophylline-) treated animals showed significant changes: a 23% (14% ns) decrease in lung resistance and a 43% (25%) increase in dynamic compliance. These changes can be interpreted as an indication of bronchodilation, since quasistatic lung compliance was unchanged. In the acetylcholine challenge test, treatment with only 10 mumol/kg zardaverine (but 300 mumol/kg theophylline) revealed significant changes compared to control measurement: a 37% (28%) lower resistance and 85% (44%) higher compliance. It has been determined that zardaverine is more than 30 times as potent as theophylline in inhibiting acetylcholine-induced bronchospasms, which is also supported by forced expiratory flow data.


Inherent limitations of probabilistic models for protein-DNA binding specificity.
The specificities of transcription factors are most commonly represented with probabilistic models. These models provide a probability for each base occurring at each position within the binding site and the positions are assumed to contribute independently. The model is simple and intuitive and is the basis for many motif discovery algorithms. However, the model also has inherent limitations that prevent it from accurately representing true binding probabilities, especially for the highest affinity sites under conditions of high protein concentration. The limitations are not due to the assumption of independence between positions but rather are caused by the non-linear relationship between binding affinity and binding probability and the fact that independent normalization at each position skews the site probabilities. Generally probabilistic models are reasonably good approximations, but new high-throughput methods allow for biophysical models with increased accuracy that should be used whenever possible.


Non-Uniform Curvature Model and Numerical Simulation for Anti-symmetric Cylindrical Bistable Polymer Composite Shells.
The bistability of anti-symmetric thin shallow cylindrical polymer composite shells, made of carbon fiber/epoxy resin, has already been investigated based on the uniform curvature and inextensible deformation assumptions by researchers in detail. In this paper, a non-uniform curvature model that considers the extensible deformations is proposed. Furthermore, a parametric modeling and automatic postprocessing plug-in component for the bistability analysis of polymer composite cylindrical shells is established by means of ABAQUS-software, by which the equilibrium configurations and the load-displacement curves during the snap process can be easily obtained. The presented analytical model is validated by the numerical simulation and literature models, while the factors affecting the bistability of anti-symmetric cylindrical shells are revisited. In addition, the planform effects of anti-symmetric cylindrical shells with rectangular, elliptical and trapezoidal planform are discussed. The results show that the presented analytical model improves the accuracy of the prediction of the principal curvature of second equilibrium configuration and agree well with the numerical results.


Amniotic fluid levels of immunoreactive monocyte chemotactic protein-1 increase during term parturition.
Parturition is characterized by an influx of inflammatory cells into gestational tissues, a phenomenon conducive to increased myometrial contractility, cervical ripening and decidual/membrane activation. Monocyte chemotactic protein-1 (MCP-1), a potent chemoattractant and activator of monocytes/macrophages, is expressed in gestational tissues and, thus, may participate in the final common pathway of labor. This study was undertaken to determine whether the amniotic fluid concentrations of immunoreactive MCP-1 are altered with gestational age or spontaneous labor at term with and without prelabor rupture of the gestational membranes. We also sought to identify intrapartum differences in the concentrations of immunoreactive MCP-1 between the upper and lower amniotic fluid compartments. A cross-sectional study was conducted to assess the concentrations of immunoreactive MCP-1 in amniotic fluid. Amniotic fluid samples were obtained from 225 women as follows: (1) women undergoing mid-trimester (14-18 weeks of gestation) amniocentesis for genetic indications, whose pregnancy outcome was normal (n = 84); (2) women in labor (n = 52) and not in labor (n = 31) at term, with intact gestational membranes; (3) women with rupture of the gestational membranes in labor (n = 18) and not in labor (n = 26), at term; and (4) women in labor at term for whom paired amniotic fluid samples were obtained through transvaginal and transabdominal amniocenteses (n = 14). Immunoreactive MCP-1 was assessed with a specific and sensitive immunoassay that had been validated for amniotic fluid. Non-parametric statistics were used for analysis. Immunoreactive MCP-1 was detected in all amniotic fluid samples. Spontaneous human parturition was associated with a significant increase in the amniotic fluid concentrations of immunoreactive MCP-1 (not in labor: median 595 pg/ml, range 183-3579 pg/ml vs. in labor: median 862 pg/ml, range 183-9609 pg/ml; p = 0.01). The median amniotic fluid concentrations of immunoreactive MCP-1 were significantly higher in the lower amniotic fluid compartment than in the upper amniotic fluid compartment (lower compartment: median 2913 pg/ml, range 1360-17080 pg/ml vs. upper compartment: median 1603 pg/ml, range 1070-8062 pg/ml; p = 0.004.). Spontaneous rupture of the gestational membranes at term was not associated with a significant change in the amniotic fluid concentrations of immunoreactive MCP-1. Immunoreactive MCP-1 is a physiological constituent of the amniotic fluid. The amniotic fluid levels of immunoreactive MCP-1 increase during spontaneous labor at term. A topographic difference in the concentration of immunoreactive MCP-1 was observed in the amniotic cavity, with higher concentrations being noted in the lower amniotic fluid compartment, as compared with the upper amniotic fluid compartment. These findings support the hypothesis that MCP-1 may play a role in the final common pathway of spontaneous labor.


Long-Term Dabigatran Treatment Delays Alzheimer's Disease Pathogenesis in the TgCRND8 Mouse Model.
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with important vascular and hemostatic alterations that should be taken into account during diagnosis and treatment. This study evaluates whether anticoagulation with dabigatran, a clinically approved oral direct thrombin inhibitor with a low risk of intracerebral hemorrhage, ameliorates AD pathogenesis in a transgenic mouse model of AD. TgCRND8 AD mice and their wild-type littermates were treated for 1 year with dabigatran etexilate or placebo. Cognition was evaluated using the Barnes maze, and cerebral perfusion was examined by arterial spin labeling. At the molecular level, Western blot and histochemical analyses were performed to analyze fibrin content, amyloid burden, neuroinflammatory activity, and blood-brain barrier (BBB) integrity. Anticoagulation with dabigatran prevented memory decline, cerebral hypoperfusion, and toxic fibrin deposition in the AD mouse brain. In addition, long-term dabigatran treatment significantly reduced the extent of amyloid plaques, oligomers, phagocytic microglia, and infiltrated T cells by 23.7%, 51.8%, 31.3%, and 32.2%, respectively. Dabigatran anticoagulation also prevented AD-related astrogliosis and pericyte alterations, and maintained expression of the water channel aquaporin-4 at astrocytic perivascular endfeet of the BBB. Long-term anticoagulation with dabigatran inhibited thrombin and the formation of occlusive thrombi in AD; preserved cognition, cerebral perfusion, and BBB function; and ameliorated neuroinflammation and amyloid deposition in AD mice. Our results open a field for future investigation on whether the use of direct oral anticoagulants might be of therapeutic value in AD.


Can instructional and emotional support in the first-grade classroom make a difference for children at risk of school failure?
This study examined ways in which children's risk of school failure may be moderated by support from teachers. Participants were 910 children in a national prospective study. Children were identified as at risk at ages 5-6 years on the basis of demographic characteristics and the display of multiple functional (behavioral, attention, academic, social) problems reported by their kindergarten teachers. By the end of first grade, at-risk students placed in first-grade classrooms offering strong instructional and emotional support had achievement scores and student-teacher relationships commensurate with their low-risk peers; at-risk students placed in less supportive classrooms had lower achievement and more conflict with teachers. These findings have implications for understanding the role that classroom experience may play in pathways to positive adaptation.


Visualization of Replisome Encounters with an Antigen Tagged Blocking Lesion.
Considerable insight is present into the cellular response to double strand breaks (DSBs), induced by nucleases, radiation, and other DNA breakers. In part, this reflects the availability of methods for the identification of break sites, and characterization of factors recruited to DSBs at those sequences. However, DSBs also appear as intermediates during the processing of DNA adducts formed by compounds that do not directly cause breaks, and do not react at specific sequence sites. Consequently, for most of these agents, technologies that permit the analysis of binding interactions with response factors and repair proteins are unknown. For example, DNA interstrand crosslinks (ICLs) can provoke breaks following replication fork encounters. Although formed by drugs widely used as cancer chemotherapeutics, there has been no methodology for monitoring their interactions with replication proteins. Here, we describe our strategy for following the cellular response to fork collisions with these challenging adducts. We linked a steroid antigen to psoralen, which forms photoactivation dependent ICLs in nuclei of living cells. The ICLs were visualized by immunofluorescence against the antigen tag. The tag can also be a partner in the Proximity Ligation Assay (PLA) which reports the close association of two antigens. The PLA was exploited to distinguish proteins that were closely associated with the tagged ICLs from those that were not. It was possible to define replisome proteins that were retained after encounters with ICLs and identify others that were lost. This approach is applicable to any structure or DNA adduct that can be detected immunologically.


A long-term visual outcome comparison in patients with optic nerve sheath meningioma managed with observation, surgery, radiotherapy, or surgery and radiotherapy.
Comparison of treatment outcome in patients with primary optic nerve sheath meningioma (ONSM). Retrospective, nonrandomized, comparative interventional case series. Sixty-four patients with at least 50 months of well-documented follow-up. Observation, surgery only, radiotherapy only, or surgery and radiotherapy. Visual acuity expressed as ratio, radiographic progression, and treatment complications. Sixty-four patients (55 women [85.9%] and nine men [14.1%]) were followed for a mean of 150.2 months (range, 51-516 months; standard deviation [SD], 74.7). The mean age at diagnosis was 47.1 years (range, 17-81 years; SD, 15.4). Fifty-eight patients had unilateral disease and six patients had bilateral disease. Of 59 patients with vision greater than no light perception at diagnosis, 13 patients were observed only, 12 had surgery only (four biopsies or partial resections, eight total resections), 18 received radiation alone, and 16 had surgery and radiation (14 biopsies or partial resections and radiation, two total resections and radiation). Irradiated patients received 4000 to 5500 cGy of conventional multiport or conformal external beam therapy, typically fractionated over 6 weeks. Visual acuity measurements at diagnosis among the four groups were not different (ratio, P = 0.186). Visual acuity at diagnosis was > or =0.5 in 56.3%, 0.4 to 0.050 in 12.5%, and <0.050 in 31.3%. Visual acuity measures at last follow-up were different among the four groups (ratio, P = 0.004). At last follow-up the acuity was > or =0.5 in 28.1%, 0.4 to 0.050 in 15.6%, and <0.050 in 56.3%. Visual acuity fell significantly for the observed only (ratio, P = 0.002), surgery only (ratio, P = 0.019), and surgery with radiation groups (ratio, P = 0.030). The radiation only group showed a decrease in visual acuity that was not significant (ratio, P = 0.301). Complication rate was 33.3% in radiation only cases, 66.7% in surgery only cases, and 62.5% in surgery with radiation cases. Twenty-one patients (32.8%) showed radiographic progression. Four patients who were observed, seven patients who had surgery alone, and eight patients who had surgery and radiation developed radiographic progression. Two patients who had radiation alone had radiographic progression before treatment. Only two patients treated with radiation only showed radiographic progression after radiotherapy, and both had at least one surgical procedure before the radiotherapy. Patients with ONSM receiving radiation alone demonstrated the best visual outcome during the follow-up period. We recommend that fractionated external beam radiation (5000-5500 cGy) be considered as initial treatment in adults in selected cases of ONSM when preservation of visual function is a reasonable therapeutic goal.


Shikonin inhibits adipogenic differentiation via regulation of mir-34a-FKBP1B.
Shikonin is a naturally occurring naphthoquinone pigment and a major constituent present in Lithospermum erythrorhizon. Since microRNAs (miRNAs) are one of the key post-transcriptional regulators of adipogenesis, their manipulation represents a potential new strategy to inhibit adipogenesis. Our aim was to investigate shikonin-dependent inhibition of adipogenesis with an emphasis on miRNA-related processes. Mir-34a increased during induced adipogenesis, and this was suppressed in the presence of shikonin. mRNA expression of FKBP1B, a suggested target of mir-34a according to bioinformatics studies, decreased during adipogenesis, but was recovered by shikonin treatment, which reversely correlated with mir-34a expression. A mir-34a inhibitor suppressed MDI-induced adipogenesis by blocking PPARγ and C/EBPα expression, while suppression of mir-34a recovered MDI-induced down-regulation of FKBP1B expression. A mir-34a mimic decreased FKBP1B mRNA expression in 3T3-L1 preadipocytes. We also observed that mir-34a bound directly to the 3'-untranslated region of FKBP1B. Finally, FKBP1B overexpression attenuated MDI-induced adipogenesis, PPARγ, and C/EBPα expression. These results suggest that mir-34a regulates adipogenesis by targeting FKBP1B expression. Our findings reveal that shikonin prevents adipogenesis by blocking the mir-34a-FKBP1B pathway which represents a promising potential target for preventing obesity.