Capturing the crystalline phase of two-dimensional nanocrystal superlattices in action.
Critical photonic, electronic, and magnetic applications of two-dimensional nanocrystal superlattices often require nanostructures in perfect single-crystal phases with long-range order and limited defects. Here we discovered a crystalline phase with quasi-long-range positional order for two-dimensional nanocrystal superlattice domains self-assembled at the liquid-air interface during droplet evaporation, using in situ time-resolved X-ray scattering along with rigorous theories on two dimensional crystal structures. Surprisingly, it was observed that drying these superlattice domains preserved only an orientational order but not a long-range positional order, also supported by quantitative analysis of transmission electron microscopy images.


TGF-β2 stimulates Tenon's capsule fibroblast proliferation in patients with glaucoma via suppression of miR-29b expression regulated by Nrf2.
To investigate the role of transforming growth factor-β2 (TGF-β2) in Tenon's capsule fibroblasts proliferation from glaucoma patients and the effect of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and miR-29b mRNA in this process. Tenon's capsule fibroblasts obtained from patients who had undergone selective glaucoma surgery (GTFs) were cultured and stimulated with 5 ng/mL TGF-β2 for 1, 3, 5, and 7 days. MTS assay was performed to detect the cell viability. Expression of Nrf2 and miR-29b was analyzed with western blot, RT-PCR and Chromatin immunoprecipitation assay (ChIP) in human fibroblast SX1412-B exposed to TGF-β2. MTS assay showed that TGF-β2 was more stimulatory on GTFs proliferation than controls. At the same time, TGF-β2 exerted an intenser effect of decreasing the Nrf2 protein and miR-29b mRNA levels in GTFs, and the level of miR-29b was effectively regulated by Ad-Nrf2. In addition, ChIP assay suggested that TGF-β2 down-regulated miR-29b expression through repressing the binding of Nrf2 to the promoter of miR-29b. Finally, we found that overexpression Nrf2 in GTFs reduced the proliferation effect on GTFs induced by TGF-β2, while miR-29b inhibitor reversed this effect. This study suggests that TGF-β2 has a time-effect relationship with Tenon's capsule fibroblasts proliferation from glaucoma patients, and it stimulates Tenon's capsule fibroblast proliferation via suppression of miR-29b expression regulated by Nrf2.


Expression profiling of human renal carcinomas with functional taxonomic analysis.
Molecular characterization has contributed to the understanding of the inception, progression, treatment and prognosis of cancer. Nucleic acid array-based technologies extend molecular characterization of tumors to thousands of gene products. To effectively discriminate between tumor sub-types, reliable laboratory techniques and analytic methods are required. We derived mRNA expression profiles from 21 human tissue samples (eight normal kidneys and 13 kidney tumors) and two pooled samples using the Affymetrix GeneChip platform. A panel of ten clustering algorithms combined with four data pre-processing methods identified a consensus cluster dendrogram in 18 of 40 analyses and of these 16 used a logarithmic transformation. Within the consensus dendrogram the expression profiles of the samples grouped according to tissue type; clear cell and chromophobe carcinomas displayed distinctly different gene expression patterns. By using a rigorous statistical selection based method we identified 355 genes that showed significant (p < 0.001) gene expression changes in clear cell renal carcinomas compared to normal kidney. These genes were classified with a tool to conceptualize expression patterns called "Functional Taxonomy". Each tumor type had a distinct "signature," with a high number of genes in the categories of Metabolism, Signal Transduction, and Cellular and Matrix Organization and Adhesion. Affymetrix GeneChip profiling differentiated clear cell and chromophobe carcinomas from one another and from normal kidney cortex. Clustering methods that used logarithmic transformation of data sets produced dendrograms consistent with the sample biology. Functional taxonomy provided a practical approach to the interpretation of gene expression data.


MOVPE Growth of GaN via Graphene Layers on GaN/Sapphire Templates.
The remote epitaxy of GaN epilayers on GaN/sapphire templates was studied by using different graphene interlayer types. Monolayer, bilayer, double-stack of monolayer, and triple-stack of monolayer graphenes were transferred onto GaN/sapphire templates using a wet transfer technique. The quality of the graphene interlayers was examined by Raman spectroscopy. The impact of the interlayer type on GaN nucleation was analyzed by scanning electron microscopy. The graphene interface and structural quality of GaN epilayers were studied by transmission electron microscopy and X-ray diffraction, respectively. The influence of the graphene interlayer type is discussed in terms of the differences between remote epitaxy and van der Waals epitaxy. The successful exfoliation of GaN membrane is demonstrated.


Circadian clock resetting by sleep deprivation without exercise in Syrian hamsters: dark pulses revisited.
Circadian rhythms in Syrian hamsters can be phase shifted by procedures that stimulate wheel running ("exercise") in the mid-subjective day (the hamster's usual sleep period). The authors recently demonstrated that keeping hamsters awake by gentle handling, without continuous running, is sufficient to mimic this effect. Here, the authors assessed whether wakefulness, independent of wheel running, also mediates phase shifts to dark pulses during the midsubjective day in hamsters free-running in constant light (LL). With running wheels locked during a 3 h dark pulse on day 3 of LL, hamsters (N = 16) averaged only 43+/-15 min of spontaneous wake time and phase shifted only 24+/-43 min. When wheels were open during a dark pulse, two hamsters remained awake, ran continuously, and showed phase advance shifts of 7.3 h and 8.7 h, respectively, whereas the other hamsters were awake <60 min and shifted only 45+/-38 min. No animals stayed awake for 3 h without running. Additional time in LL (10 and 20 days) did not potentiate the waking or phase shift response to dark pulses. When all hamsters were sleep deprived with wheels locked during a dark pulse, phase advance shifts averaged 261+/-110 min and ranged up to 7.3 h. These shifts are large compared to those previously observed in response to the 3 h sleep deprivation procedure. Additional tests revealed that this potentiated shift response is dependent on LL prior to sleep deprivation but not LL after sleep deprivation. A final sleep deprivation test showed that a small part of the potentiation may be due to suppression of spontaneous wheel running by LL. These results indicate that some correlate of waking, other than continuous running, mediates the phase-shifting effect of dark pulses in the mid-subjective day. The mechanism by which LL potentiates shifting remains to be determined. The lack of effect of subsequent LL on the magnitude of shifts to sleep deprivation in the dark suggests that LL reduces responsivity to light by processes that take >3 h of dark to reverse.


Synthesis of Furo[2,3-c]pyridazines via Tandem Transition-Metal Catalysis.
A general and efficient catalytic approach to synthesis of the furo[2,3-c]pyridazine ring system is reported. Building on the easily accessible 2-bromo-3-aminopyridizinone skeleton, a tandem Sonogashira coupling-cycloisomerization provides ready access to functionalized furopyridazines. A wide functional group tolerance was observed in the tandem reaction, which proceeds in high yield in 1-3 h. The structure of the heterocyclic ring system was confirmed through single-crystal X-ray crystallography.


Inclusion complexation of p-hydroxybenzoic acid esters with 2-hydroxypropyl-beta-cyclodextrins. On changes in solubility and antimicrobial activity.
To obtain a transparent and effective solution of p-hydroxybenzoic acid esters (parabens), the use of 2-hydroxypropyl-beta-cyclodextrins (2-HP-beta-CyDs) as solubilizers with different degrees of substitution (D.S.) was surveyed. 2-HP-beta-CyDs significantly increased the aqueous solubility of four kinds of parabens (methyl < ethyl < propyl < butyl esters), where the solubilizing ability decreased with an increase in the D.S. of the 2-hydroxypropyl group in beta-CyD. The antimicrobial activity of the parabens tended to decrease by complexation with 2-HP-beta-CyDs. However, the activity could be maintained by lengthening the alkyl chain of the parabens. 1H- and 13C-nuclear magnetic resonance and circular dichroism spectroscopic studies suggest that the hydrophobic alkyl moiety of butyl paraben is preferably included in the cavity, and the phenol group extrudes from the cavity. The present results suggest that a suitable combination of 2-HP-beta-CyDs and hydrophobic, longer alkyl parabens is useful for the preservation of liquid formulations.


BCCTBbp: the Breast Cancer Campaign Tissue Bank bioinformatics portal.
BCCTBbp (http://bioinformatics.breastcancertissue bank.org) was initially developed as the data-mining portal of the Breast Cancer Campaign Tissue Bank (BCCTB), a vital resource of breast cancer tissue for researchers to support and promote cutting-edge research. BCCTBbp is dedicated to maximising research on patient tissues by initially storing genomics, methylomics, transcriptomics, proteomics and microRNA data that has been mined from the literature and linking to pathways and mechanisms involved in breast cancer. Currently, the portal holds 146 datasets comprising over 227,795 expression/genomic measurements from various breast tissues (e.g. normal, malignant or benign lesions), cell lines and body fluids. BCCTBbp can be used to build on breast cancer knowledge and maximise the value of existing research. By recording a large number of annotations on samples and studies, and linking to other databases, such as NCBI, Ensembl and Reactome, a wide variety of different investigations can be carried out. Additionally, BCCTBbp has a dedicated analytical layer allowing researchers to further analyse stored datasets. A future important role for BCCTBbp is to make available all data generated on BCCTB tissues thus building a valuable resource of information on the tissues in BCCTB that will save repetition of experiments and expand scientific knowledge.


Picosecond time-resolved laser pump/X-ray probe experiments using a gated single-photon-counting area detector.
The recent developments in X-ray detectors have opened new possibilities in the area of time-resolved pump/probe X-ray experiments; this article presents the novel use of a PILATUS detector to achieve X-ray pulse duration limited time-resolution at the Advanced Photon Source (APS), USA. The capability of the gated PILATUS detector to selectively detect the signal from a given X-ray pulse in 24 bunch mode at the APS storage ring is demonstrated. A test experiment performed on polycrystalline organic thin films of alpha-perylene illustrates the possibility of reaching an X-ray pulse duration limited time-resolution of 60 ps using the gated PILATUS detector. This is the first demonstration of X-ray pulse duration limited data recorded using an area detector without the use of a mechanical chopper array at the beamline.


Revisiting Poststroke Upper Limb Stratification: Resilience in a Larger Cohort.
Upper limb (UL) impairment in stroke survivors is both multifactorial and heterogeneous. Stratification of motor function helps identify the most sensitive and appropriate assessments, which in turn aids the design of effective and individualized rehabilitation strategies. We previously developed a stratification method combining the Grooved Pegboard Test (GPT) and Box and Block Test (BBT) to stratify poststroke UL motor function. To investigate the resilience of the stratification method in a larger cohort and establish its appropriateness for clinical practice by investigating limitations of the GPT completion time. Post hoc analysis of motor function for 96 community-dwelling participants with stroke (n = 68 male, 28 female, age 60.8 ± 14 years, 24.4 ± 36.6 months poststroke) was performed using the Wolf Motor Function Test (WMFT), Fugl-Meyer Assessment (F-M), BBT, and GPT. Hypothesis-free and hypothesis-based hierarchical cluster analyses were conducted to determine the resilience of the stratification method. The hypothesis-based analysis identified the same functional groupings as the hypothesis-free analysis: low (n = 32), moderate (n = 26), and high motor function (n = 38), with 3 exceptions. Thirty-three of the 38 participants with fine manual dexterity completed the GPT in ≤5 minutes. The remaining 5 participants took 6 to 25 minutes to place all 25 pegs but used alternative movement strategies to complete the test. The GPT time restriction changed the functional profile of the moderate and high motor function groups leading to more misclassifications. The stratification method unambiguously classifies participants by UL motor function. While the inclusion of a 5-minute cutoff time for the GPT is preferred for clinical practice, it is not recommended for stratification purposes.


[Effectiveness of different maintenance methods for codonopsis radix].
To observe different maintenance methods including vacuum-packing, storage together with tobacco, storage together with fennel, ethanol steam and sulfur fumigation for the protection of Codonopsis Radix against mildew and insect damage, and to analyze the content of polysaccharide and flavonoids of Codonopsis Radix tested in this studies, so as to look for the scientific maintenance methods replacing traditional sulfur fumigation. Except for the sulfur fumigation, naturally air-dried Codonopsis Radix was used to investigate the maintenance effectiveness of the above methods, respectively. Mildew was observed by visual inspection, and the content of polysaccharide and flavonoids were determined by ultra-violet and visible spectrophotometer. Comprehensive evaluation was given based on the results of the different maintenance methods. Low-temperature vacuum-packing, ambient-temperature vacuum-packing and sulfur fumigation could keep Codonopsis Radix from mildew and insect damage for one year, but ambient-temperature vacuum-packing showed flatulent phenomenon; ethanol steam could keep Codonopsis Radix from mildew and insects for over half a year; storage together with tobacco or fennel did not have maintenance effect. The difference of polysaccharide and flavonoids contents of all tested Codonopsis Radix was not statistically significant. Low temperature vacuum-packing maintenance can replace traditional sulfur fumigation, and it can maintain the quality of Codonopsis Radix to a certain extent.


Induction and molecular properties of secretory and serum IgA antibodies specific for environmental antigens.
A generalized secretory IgA response can be induced by ingestion of various antigens due to dissemination of sensitized precursors of IgA plasma cells from gut-associated lymphoid tissue to various secretory glands. Oral ingestion of a bacterial antigen by volunteers led to the parallel appearance of secretory IgA antibodies in several external secretions that was preceded by a transitory detection of IgA antibody-secreting cells in the peripheral blood. Naturally occurring secretory and serum IgA antibodies as well as secretory and serum antibodies induced by mucosal immunization belong predominantly to the IgA1 subclass; however, in external secretions IgA2 is the predominant subclass of natural antibodies to endotoxin and lipoteichoic acid. Although in external secretions specific IgA antibodies are of polymeric form, serum IgA antibodies to different antigens display considerable variability with respect to their distribution in polymeric and monomeric forms. However, after experimental infection, serum IgA antibodies to the influenza virus hemagglutinin are almost exclusively polymeric.


Application of a computer-based neurocognitive assessment battery in the elderly with and without hearing loss.
Due to demographic changes, the number of people suffering not only from dementia illness but also from hearing impairment with the need for hearing rehabilitation have increased noticeably. Even with the association between hearing, age, and cognitive decline being well known, this issue has so far not played an important role in daily clinical Ear Nose Throat settings. The aim of the present study was to evaluate the use of a computer-based battery of tests of neurocognitive abilities in older patients with and without hearing loss. A total of 120 patients aged 50 years and older were enrolled in this prospective clinical study: 40 patients suffered from severe bilateral hearing loss and were tested before cochlear implantation and 80 patients showed normal hearing thresholds between 500 and 4,000 Hz bilaterally. The test battery covered a wide range of cognitive abilities such as long- and short-term memory, working memory (WM), attention, inhibition, and other executive functions. Individuals with severe depression or cognitive impairment were excluded. Hearing status was a significant predictor of performance on delayed recall (P=0.0082) and verbal fluency after adjusting for age (P=0.0016). Age predominantly impacted on inhibition (P=0.0039) and processing speed (P<0.0001), whereas WM measured by the Operation Span task (OSPAN) and the attention were influenced by both age and hearing. The battery of tests was feasible and practical for testing older patients without prior computer skills. A computerized neurocognitive assessment battery may be a suitable tool for the elderly in clinical practice. While it cannot replace a thorough neuropsychological examination, it may help to draw the line between cognitive and hearing impairment in the elderly and enable the development of individual strategies for hearing rehabilitation.


Clinical effects of rectal retractor application in prostate cancer radiotherapy.
Background: Radiation-induced rectal toxicities remain as a major risk during prostate radiotherapy. One approach to the reduction of rectal radiation dose is to physically increase the distance between the rectal wall and prostate. Therefore, the aim of this study was to evaluate whether the application of the rectal retractor (RR) can reduce rectal dose and toxicity in prostate cancer 3-dimensional conformal radiotherapy (3D-CRT). Methods: Overall, 36 patients with localized prostate cancer were randomized into the 2 groups, 18 patients with RR in-place and 18 without RR. All patients underwent planning computed tomography (CT). Patients were treated with 70 Gy in 35 fractions of 3D-CRT. In the RR group, RR was used during cone-down 20 treatment fractions. Acute and late gastrointestinal (GI) toxicities were assessed using EORTC/RTOG scoring system weekly during radiotherapy, 3, and 12 months after treatment. Device-related events were recorded according to CTCAE version 4.0. Patient characteristics, cancer differences, and dosimetric data for the RR and non-RR groups were compared using a Man-Whitney U test for continuous variables, and Fisher exact test for categorical data. The EORTC/RTOG scores for the 2 groups were compared using Fisher exact test. A P value <0.05 was considered statistically significant. Results: A RR significantly reduced mean dose (Dmean) to the rectum as well as rectal volume receiving 50% to 95% (V50-95%) of prescribed dose. The absolute reduction of rectal Dmean was 10.3 Gy. There was no statistically significant difference in acute GI toxicity between groups during treatment or at 3 months. At 12 months, 2 patients in the RR group and 9 in the control group experienced late grade ≥ 1 GI toxicity (p=0.027). No patients in the RR group reported late grade ≥ 2 GI toxicity, whereas 3 patients in the control group experienced late grade 2 GI toxicity. In the RR group, 6 patients reported grade 1 rectal discomfort and pain according to CTCAE version 4.0. Conclusion: The application of the RR showed a significant rectum sparing effect, resulting in substantially reducing late GI toxicity.


Peripheral neuropathy associated with angioimmunoblastic lymphadenopathy.
A 49-year-old man developed mononeuritis multiplex associated with angioimmunoblastic lymphadenopathy. The biopsy of the sural nerve revealed focal reduction of myelinated fibres and axonal degeneration, as well as perivascular inflammatory infiltrates composed of lymphocytes and plasma cells, exhibiting policlonal immunoglobulin expression, proliferation of blood vessels, thickening of the vessel wall and endothelial hyperplasia. These latter changes are similar to those commonly encountered in the lymph nodes, as well as in other organs, in patients suffering from angioimmunoblastic lymphadenopathy.


Decision and experience: why don't we choose what makes us happy?
Recent years have witnessed a growing interest among psychologists and other social scientists in subjective well-being and happiness. Here we review selected contributions to this development from the literature on behavioral-decision theory. In particular, we examine many, somewhat surprising, findings that show people systematically fail to predict or choose what maximizes their happiness, and we look at reasons why they fail to do so. These findings challenge a fundamental assumption that underlies popular support for consumer sovereignty and other forms of autonomy in decision-making (e.g. marriage choice), namely, the assumption that people are able to make choices in their own best interests.


Postharvest Ultraviolet Radiation in Fruit and Vegetables: Applications and Factors Modulating Its Efficacy on Bioactive Compounds and Microbial Growth.
Ultraviolet (UV) radiation has been considered a deleterious agent that living organisms must avoid. However, many of the acclimation changes elicited by UV induce a wide range of positive effects in plant physiology through the elicitation of secondary antioxidant metabolites and natural defenses. Therefore, this fact has changed the original UV conception as a germicide and potentially damaging agent, leading to the concept that it is worthy of application in harvested commodities to take advantage of its beneficial responses. Four decades have already passed since postharvest UV radiation applications began to be studied. During this time, UV treatments have been successfully evaluated for different purposes, including the selection of raw materials, the control of postharvest diseases and human pathogens, the elicitation of nutraceutical compounds, the modulation of ripening and senescence, and the induction of cross-stress tolerance. Besides the microbicide use of UV radiation, the effect that has received most attention is the elicitation of bioactive compounds as a defense mechanism. UV treatments have been shown to induce the accumulation of phytochemicals, including ascorbic acid, carotenoids, glucosinolates, and, more frequently, phenolic compounds. The nature and extent of this elicitation have been reported to depend on several factors, including the product type, maturity, cultivar, UV spectral region, dose, intensity, and radiation exposure pattern. Even though in recent years we have greatly increased our understanding of UV technology, some major issues still need to be addressed. These include defining the operational conditions to maximize UV radiation efficacy, reducing treatment times, and ensuring even radiation exposure, especially under realistic processing conditions. This will make UV treatments move beyond their status as an emerging technology and boost their adoption by industry.


Upper Airway Nerve Block for Rigid Bronchoscopy in the Patients with Tracheal Stenosis: A Case Serie.
Rigid bronchoscopy is often used to diagnose and treat the location of resection of the tracheal stenosis. It is a selective procedure for the dilatation of tracheal stenosis, especially when accompanied by respiratory distress. We introduced patients who were diagnosed with tracheal stenosis and candidate for rigid bronchoscopy dilatation by the upper airway nerve blocks. This prospective observational study was conducted on 17 patients who underwent dilatation with rigid bronchoscopy in tracheal stenosis at Hospitals affiliated with Babol University of Medical Sciences from 2002 to 2017. The patients were given three nerve blocks, 6 bilateral superior laryngeal nerve block, bilateral glossopharyngeal nerve block, and recurrent laryngeal nerve block (transtracheal) before awake rigid bronchoscopy using 2% lidocaine. We evaluated the demographic data, the cause of tracheal stenosis, the quality of the airway nerve block (Intubation score), patients' satisfaction from bronchoscopy and thoracic surgeons' satisfaction. Complications of nerve blocks were recorded. From 2002 to 2017, 17 patients (14 were male and 3 were) female with tracheal stenosis who were candidates for dilatation with bronchoscopy and accepted the upper nerve block were included. The quality of the block was acceptable in 16 (94%) patients. 15 patients received fentanyl, and only two patients did not need to intravenous sedation. The mean age of patients was 29.59 ± 11.59. The average satisfaction of the surgeon was 8.82 ± 1.13 and the satisfaction of patients with anesthesia was 8.89 ± 1.16. There was one serious complication (laryngospasm) in one patient. The upper airway nerve block method is a suitable anesthesia technique for patients with tracheal stenosis who are candidates for the tracheal dilatation with rigid bronoscopy, especially when the patient has respiratory distress and has not been evaluated before surgery.


[Pet ownership and health status of pets from immunocompromised children, with emphasis in zoonotic diseases].
To characterize pet ownership and pet health status in families of immunocompromised (IS) children, with emphasis in zoonotic diseases. Families of IS children from two hospitals in Santiago, Chile, were interviewed and their pets were evaluated by veterinary examination, coproparasitologic and skin dermatophytes test. In specific cases, other laboratory tests were performed in IS children or their relatives. 47 out of 70 contacted families had pets, 42 participated in the study. Several risk factors for IS children were observed, as having a turtle as a pet and to clean cat or turtle faeces. Lack of adequate veterinary control, immunizations and deparasitation of pets were observed. Some animals showed zoonotic diseases or agents, as Brucella canis, Cryptosporidium sp, Giardia intestinalis, Toxocara canis and scabies. 44% of dogs had ticks and 37% had fleas, both potential vectors of infections. Our results suggest that policies to provide safer pet contact in IS children are needed.


Nonsyndromic X-linked hearing loss.
To date, 135 loci and 50 genes have been identified as causes of nonsyndromic hearing loss. Until recently, four loci (DFN2, DFN3, DFN4, and DFN6) had been implicated in nonsyndromic X-linked hearing loss; however, a new classification (DFNX1-5) has been proposed to reduce confusion in the terminology. The different types of nonsyndromic X-linked hearing loss demonstrate various clinical features in terms of the onset and progressiveness of hearing loss, pattern of audiogram, and the presence or absence of inner ear malformations. In addition to the POU3F4 gene, which was the first gene identified as causing nonsyndromic X-linked hearing loss, a second gene, PRPS1, has recently been identified to be the causative gene of DFNX1 (DFN2). This study reviews the new classification system, as well as the clinical features, molecular genetics, and developmental pathogenesis of different forms of nonsyndromic X-linked hearing loss.


Targeting the vitamin biosynthesis pathways for the treatment of malaria.
The most severe form of malaria is Malaria tropica, caused by Plasmodium falciparum. There are more than 1 billion people that are exposed to malaria parasites leading to more than 500,000 deaths annually. Vaccines are not available and the increasing drug resistance of the parasite prioritizes the need for novel drug targets and chemotherapeutics, which should be ideally designed to target selectively the parasite. In this sense, parasite-specific pathways, such as the vitamin biosyntheses, represent perfect drug-target characteristics because they are absent in humans. In the past, the vitamin B9 (folate) metabolism has been exploited by antifolates to treat infections caused by malaria parasites. Recently, two further vitamin biosynthesis pathways - for the vitamins B6 (pyridoxine) and B1 (thiamine) - have been identified in Plasmodium and analyzed for their suitability to discover new drugs. In this review, the current status of the druggability of plasmodial vitamin biosynthesis pathways is summarized.


Developmental Changes in Time and Space Promote Evolutionary Diversification of Flowers: A Case Study in Dipsacoideae.
Diversification in flower shape and function is triggered by the high plasticity of flower meristems. Minute changes in space and time can profoundly affect the formation of adult structures. Dipsacoideae provides an excellent model system to investigate the evolutionary aspects of temporal and spatial changes in flower development due to its small size, the resolved phylogenetic framework, and significant diversity of perianth form and merosity. In the present study, we investigated the sequence of floral organ initiation and quantified the interactions between flower meristem expansion and petal primordium size in eight species representing two major clades of Dipsacoideae. Our quantitative study indicates the plasticity of the flower meristem for the regulation of pentamery either due to a decrease in petal primordium size (Scabiosa) or an increase in flower meristem size (Pterocephalus and Lomelosia) compared to tetramerous flowers. According to our results, temporal shifts of organ initiation during flower evolution contribute to the morphological diversity of perianth. Sepal reduction in members of the Dipknautids is paralleled by a delay in sepal initiation. The multiplication of sepals in Lomelosia and Pterocephalus is correlated with an extension of initiation time. Some heterochronies in early development do not affect adult morphology. The effects of a temporal change in early development can be enhanced, reduced, or eliminated by later changes of the growth rate during development. Our results confirm the hypothesis that the interaction between timing and space plays an important role for evolutionary diversification of flowers.


Concussive head injury in children and adolescents.
Awareness of concussive head injury continues to grow, aided by greater understanding of the neurobiological underpinnings of concussions and its short-term and long-term consequences. Younger players who are in the midst of their neurodevelopmental trajectory continue to be placed at risk; therefore, more must be done to educate clinicians, parents, coaches and players alike in this area. Our understanding of concussive injury is evolving and more integrated models of care are being developed so as to provide patients with the holistic model of care needed in the post-concussive context. In this article, we outline a contemporary perspective on concussion, and address an evidence-based approach to children and adolescents who have suffered a concussive injury. Good clinical care of a patient with concussion by the primary care physician is the best prevention of adverse outcomes. The ability of the primary care physician to recognise when to treat and when to refer will be an important agent for change in this field.


The neuroscience of Helmholtz and the theories of Johannes Müller. Part 2: Sensation and perception.
In this, our continuation paper on Helmholtz and Müller, we examine Helmholtz's contributions to sensation and perception, with emphasis on his extension and modification of Müller's theory of specific nerve energies. The material is again presented in biographical-chronological context. We also examine Helmholtz's views on depth and space perception, and his empirical theory of knowledge, which are also compared to Müller's views. It will be shown that Helmholtz remained stimulated by the thoughts and doctrines of Johannes Müller in the sensory-perceptual part of his career, which began early in the 1850s and ended with his death. Nevertheless, Helmholtz's own experiments and new discoveries by others sometimes led him to quite different conclusions.


Left ventricular stroke volume determinations from radionuclide ventriculograms: the effects of photon attenuation.
To improve the accuracy of scintigraphic ventricular volume determination, which is limited by photon attenuation between the heart and the gamma camera, a method was developed for directly measuring the photon attenuation of radioactivity delivered as a bolus through a Swan-Ganz catheter into the right atrium. Comparison of the count rate recovered from this bolus with the total ex vivo measured activity determined by imaging an aliquot of the administered activity allowed calculation of the attenuation factor. Left ventricular stroke volumes determined scintigraphically by the count method in gated blood pool studies and then corrected with this attenuation factor correlated well with stroke volumes determined from thermodilution cardiac output and heart rate (r = 0.92; SEE, 6.1 ml). The agreement between the two measurements was markedly less when an average attenuation factor was employed for correction of scintigraphic volumes (r = 0.52; SEE, 14.8 ml). The results indicate that correction for photon attenuation is needed for accurate measurement of left ventricular volumes. Correction of left ventricular counts based on body weight or body surface area improves the accuracy of volume estimates.


The influence of the root cross-section on the stress distribution in teeth restored with a positive-locking post and core design: a finite element study.
Human teeth with substantial coronal defects are subject to reconstruction by means of post and core restorations. Typically, such a restoration comprises a slightly cylindrical post onto which an abutment of varying shape, depending on the designated restoration, is attached. As clinical results are not satisfactory to date, we proposed a new proprietary post and core design which makes use of positive locking. As this prefabricated system is not customised to an individual root's cross-sectional geometry (usually oval), a varying amount of radicular dentin is left in periphery of the core's outer edge. The aim of this study was to assess the implications of this fact, i.e., whether the root has to endure higher overall stress levels which ultimately may lead to failure of one of the components involved. A series of finite element simulations were performed to evaluate stress and strain on the system, in which the proposed post and core was embedded into a virtual dentin cylinder of different diameters, ranging from flush mounting of the restoration to a dentin excess of 4 mm, and subsequently loaded with forces with two angles of attack (90 degrees and 130 degrees ). The results show that flush mounting yields an agreeable stress and strain distribution within the radicular dentin, but overall stress levels drop significantly with an excess of 0.5 mm of surrounding dentin. More than 1 mm excess was not found to have profound positive effects.


Prevalence of Helicobacter pylori infection in patients with large gastric folds: evaluation and follow-up with endoscopic ultrasound before and after antimicrobial therapy.
Large gastric folds may result from infectious, inflammatory, neoplastic, vascular, and infiltrative disorders involving a part or the entire gastric wall. Helicobacter pylori infection of the gastric mucosa is associated with an active gastritis characterized by infiltration of the mucosa and submucosa with neutrophils, eosinophils, macrophages, and lymphocytes. The purposes of the study were: 1) to study patients with large gastric folds noted on computed tomography, upper gastrointestinal series, or endoscopy, with endoscopy and biopsies and endoscopic ultrasound to determine the prevalence of H. pylori infection and the location of the thickening within the gastric wall; 2) to reexamine H. pylori-infected patients with EUS after antimicrobial therapy to determine whether resolution of the wall thickening accompanied eradication of H. pylori and improvement of histological gastritis. Thirty-two patients with thickened gastric folds were studied. Eighteen patients had H. pylori infection and were treated with amoxicillin 1 g b.i.d. and omeprazole 40 mg b.i.d. x 14 days. One month after antimicrobial therapy, patients were reexamined by EUS, and gastric biopsies were obtained. Eighteen of 32 patients had H. pylori infection and gastritis. In the H. pylori-infected patients with gastritis, EUS demonstrated diffuse thickening of the inner three layers (mucosa-lumen interface, deep mucosa, submucosa) without thickening of the 4th and 5th layers of the gastric wall. After antimicrobial therapy and resolution of gastritis, EUS demonstrated concomitant resolution of this thickening and normalization of layers 1-3. H. pylori gastritis is a common cause of gastric wall thickening. EUS allows intrinsic localization of the gastric wall thickening in patients with large gastric folds and H. pylori infection and documents the resolution of this wall thickening upon eradication of H. pylori and resolution of gastritis.


Heart Failure Disturbs Gut-Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite.
Trimethylamine (TMA) is a gut bacteria product oxidized by the liver to trimethylamine-N-oxide (TMAO). Clinical evidence suggests that cardiovascular disease is associated with increased plasma TMAO. However, little headway has been made in understanding this relationship on a mechanistic and molecular level. We investigated the mechanisms affecting plasma levels of TMAO in Spontaneously Hypertensive Heart Failure (SHHF) rats. Healthy Wistar Kyoto (WKY) and SHHF rats underwent metabolic, hemodynamic, histopathological and biochemical measurements, including tight junction proteins analysis. Stool, plasma and urine samples were evaluated for TMA and TMAO using ultra performance liquid chromatography-mass spectrometry. SHHF presented disturbances of the gut-blood barrier including reduced intestinal blood flow, decreased thickness of the colonic mucosa and alterations in tight junctions, such as claudin 1 and 3, and zonula occludens-1. This was associated with significantly higher plasma levels of TMA and TMAO and increased gut-to-blood penetration of TMA in SHHF compared to WKY. There was no difference in kidney function or liver oxidation of TMA to TMAO between WKY and SHHF. In conclusion, increased plasma TMAO in heart failure rats results from a perturbed gut-blood barrier and increased gut-to-blood passage of TMAO precursor, i.e., TMA. Increased gut-to-blood penetration of bacterial metabolites may be a marker and a mediator of cardiovascular pathology.


[Prevalence of peptic ulcer and its associated factors in elderly people in Beijing].
Survey on the prevalence rate of peptic ulcer (PU) and its associated factors in 3440 elderly people aged 60 or above, living in some area of Beijing is reported in the paper. The survey was carried out from July to October, 1993 through administration of household questionnaire. Result showed that the prevalence rate of PU was 4.1%, higher among males (5.3%) than in females (2.9%). There were more, younger, elderly and more farmers living in mountainous areas suffered from the disease than, older, elderly and rural farmers or urbanial residents. It is demonstrated that depression, intelle ctual work, cigarette smoking, heavy alcohol intake and higher educational level were correlated with the occurrence of the disease in the elderly. Neither dietary structure or light alcohol intake was found to be associated with prevalence of PU with statistical significance. We revealed that the prevalent rates of PU in the elderly were different according to age, sex, geographic area, educational level and professional aspects. The influence of psychological factors to the prevalence rate of PU should also be considered.


Highly Efficient Magnetic Propulsion of NiFe Nanorod-Based Miniature Swimmers in Three Dimensions.
Magnetically actuated miniature robots have attracted the attention of the scientific community over the past two decades, but the confined workspace of their manipulation system (typically a tri-axial coil or eight electromagnetic coils) and the low efficiency of propulsion have limited their utility. Here, we describe a highly efficient NiFe nanorod-based magnetic miniature swimmer that can be manipulated in 3D spaces using two pairs of coils placed in the x-y horizontal plane. In the new swimmer, the shape symmetry is broken along its body, and the asymmetry in magnetizations is introduced perpendicular to the long axis of its body simultaneously. Such a combined asymmetry design offers favorable controllability in planar magnetic fields, which relaxes the multi-axial coil requirement of the commonly used manipulation system and thus reduces the restriction on the shape and size of the workspaces. The new swimmers display efficient 3D propulsion, with a speed of over 5000 μm s-1 (∼3 body length s-1) and powerful locomotion in biological media such as raw human blood. The fuel utilization efficiency of the swimmer, defined as the ratio of the distance to the net input work in one period, was estimated to be approximately from 10-2 to 10-3 m/J, which is significantly higher than that of magnetic motors with a slender body. Moreover, to provide practical support for further potential use, we demonstrated that the swimmer is able to perform incision operations as a minimally invasive microsurgical tool. Such a swimmer actuation strategy provides a simple and efficient way for 3D manipulation of magnetic miniature robots, offering great potential for future biomedical and other applications.


[Role of perioperative biological tests during the performance and follow-up of corticotroph adenoma exeresis].
ACTH assay in cavernous sinus samples during resection of pituitary adrenocorticotroph adenomas is a simple and safe technique providing an intraoperative assessment of adrenocorticotroph hormone gradients. Bilateral puncture of the cavernous sinus can be achieved vial the standard transsphenoidal approach to the sella turcica. ACTH is determined with IRMA at 37;C with an incubation time of less than one hour. Among 71 cases in our experience, the ACTH gradient accurately predicted the position of the adenoma in 93% of the cases. This rate is higher than the 61% accuracy reported for inferior petrosal sinus sampling. The technique reported is more precise than MRI which correctly identifies adenomas in only 50% of the cases. The remaining cases are either false positives or false negatives. We report an 82% cure rate either via direct resection of the microadenoma or via partial hypophysectomy guided by the ACTH gradient. In our series, 20 cases of Cushing's disease had a normal MRI and no surgically identifiable adenoma. In 10 of these cases however, cure was achieved by performing ACTH gradient guided partial hypophysectomy. This method produces no morbidity and is most helpful for the neurosurgeon allowing confirmation of the position of an MRI-visible adenoma or an adenoma identified intraoperatively. It does not however replace neurosurgical experience which remains the most important predictive factor for outcome in surgical treatment of Cushing's disease.


The role of positive costimulatory molecules in transplantation and tolerance.
The manipulation of costimulatory pathways holds tremendous potential for treating immunologically mediated diseases. In this article, we review the role of molecules that deliver a positive second signal that, together with an antigen-specific signal from the T-cell receptor, is necessary to promote complete T-cell activation, differentiation and development of effector function. Numerous positive costimulatory molecules have been identified: CD28/B7, induced costimulatory/induced costimulatory ligand, CD40/CD154, OX40/OX40L, CD27/CD70, 4-1BB/4-1BBL, LIGHT/herpes virus entry mediator, glucosyltransferase R and T-cell immunoglobulin mucin molecules. Many of these have been only recently discovered and remain incompletely studied. Recent work has demonstrated that some costimulatory molecules bind ligands expressed by nonprofessional activated protein C, some modulate regulatory T cells and some sustain rather than initiate immune responses. Emerging data suggest that the costimulatory pathways are redundant and that the various costimulatory molecules affect different T-cell populations and act at different times during the course of the immune response. These observations suggest that the therapeutic exploitation of strategies targeting costimulatory molecules will require carefully timed interventions directed against multiple pathways.


Flexner revisited: the role and value of the basic sciences in medical education.
A central tenet of Flexner's report was the fundamental role of science in medical education. Today, there is tension between the time needed to teach an ever-expanding knowledge base in science and the time needed for increased instruction in clinical application and in the behavioral, ethical, and managerial knowledge and skills needed to prepare for clinical experiences. One result has been at least a perceived reduction in time and focus on the foundational sciences. In this context, the International Association of Medical Science Educators initiated a study to address the role and value of the basic sciences in medical education by seeking perspectives from various groups of medical educators to five questions: (1) What are the sciences that constitute the foundation for medical practice? (2) What is the value and role of the foundational sciences in medical education? (3) When and how should these foundational sciences be incorporated into the medical education curriculum? (4) What sciences should be prerequisite to entering the undergraduate medical curriculum? (5) What are examples of the best practices for incorporating the foundational sciences into the medical education curriculum? The results suggest a broad group of experts believes that an understanding of basic science content remains essential to clinical practice and that teaching should be accomplished across the entire undergraduate medical education experience and integrated with clinical applications. Learning the sciences also plays a foundational role in developing discipline and rigor in learners' thinking skills, including logical reasoning, critical appraisal, problem solving, decision making, and creativity.


Local control of granule cell generation by cerebellar Purkinje cells.
Cerebellar Purkinje cells were ablated by the specific expression of diphtheria toxin in these cells in transgenic mice. Purkinje cell degeneration during early postnatal development shows a zonally restricted pattern which has been exploited in order to look for local secondary effects. The most obvious early effect is the alignment of gaps in the Purkinje cell layer with dramatically thinned zones in the overlying EGL, the germinal layer from which granule cells are generated. Within these EGL zones in the transgenic mutant, markers that distinguish matrix from mantle cells demonstrate a preferential loss of the proliferative cells. Comparison of BrdU incorporation in the mutant vs wild-type confirms the reduction in proliferation. In the mutant, in situ labeling of DNA fragmentation associated with apoptotic cell death shows abundant labeling of granule cells that have exited the EGL, but not of progenitor cells in the EGL. Thus, although a trophic role for Purkinje cells has been well documented, these observations further suggest a mitogenic role which can be exerted locally.


The anatomy of the small saphenous vein: fascial and neural relations, saphenofemoral junction, and valves.
Varicose veins are a frequent burden, also in the small saphenous system. Yet its basic anatomy is not described consistently. We therefore investigated the fascial and neural relationships of the small saphenous vein (SSV) as well as the frequency and position of valves and the different junctional patterns, also considering the thigh extension. We dissected the legs of 51 cadavers during the regular dissection course held in winter 2007 at Innsbruck Medical University, with a total of 86 SSVs investigable proximally and 94 SSVs distally. A distinct saphenous fascia is present in 93 of 94 cases. It starts with a mean distance of 5.1 cm (SD 1.2 cm) proximal to the calcaneal tuber, where the tributaries to the SSV join to form a common trunk. The neural topography at the level of the gastrocnemius muscle's origins shows the medial sural cutaneous nerve in 88% medially and in 12% laterally to the SSV, the tibial nerve in 64% medially and in 36% laterally, and the common fibular nerve in 98% medially and in 2% laterally to the vein. The saphenopopliteal junction (SPJ) resembled in about 37% type A (UIP-classification), 15% type B, and 24% type C. A total of 17% of specimens showed a venous web or star at the popliteal fossa and 6% had a doubled junction. A thigh extension could be demonstrated in about 84%. A most proximal valve was present in only 94% at a mean distance of 1.2 cm (SD 1.4 cm) to the SSVs orifice. A consecutive distal valve was only present in 65% with a mean distance of 5.1 cm (SD 2.3 cm). Two fascial points or regions can be described in the SSVs' course and its own saphenous fascia is demonstrated macroscopically in almost all cases. The neural topography is highly individual. The SPJ is highly individual where we found hitherto unclassified patterns in a remarkable number of veins. Venous valves are not as frequent as we supposed them to be. Furthermore, not all most proximal valves seem to be terminal valves.


Fast and robust multimodal image registration using a local derivative pattern.
Deformable multimodal image registration, which can benefit radiotherapy and image guided surgery by providing complementary information, remains a challenging task in the medical image analysis field due to the difficulty of defining a proper similarity measure. This article presents a novel, robust and fast binary descriptor, the discriminative local derivative pattern (dLDP), which is able to encode images of different modalities into similar image representations. dLDP calculates a binary string for each voxel according to the pattern of intensity derivatives in its neighborhood. The descriptor similarity is evaluated using the Hamming distance, which can be efficiently computed, instead of conventional L1 or L2 norms. For the first time, we validated the effectiveness and feasibility of the local derivative pattern for multimodal deformable image registration with several multi-modal registration applications. dLDP was compared with three state-of-the-art methods in artificial image and clinical settings. In the experiments of deformable registration between different magnetic resonance imaging (MRI) modalities from BrainWeb, between computed tomography and MRI images from patient data, and between MRI and ultrasound images from BITE database, we show our method outperforms localized mutual information and entropy images in terms of both accuracy and time efficiency. We have further validated dLDP for the deformable registration of preoperative MRI and three-dimensional intraoperative ultrasound images. Our results indicate that dLDP reduces the average mean target registration error from 4.12 mm to 2.30 mm. This accuracy is statistically equivalent to the accuracy of the state-of-the-art methods in the study; however, in terms of computational complexity, our method significantly outperforms other methods and is even comparable to the sum of the absolute difference. The results reveal that dLDP can achieve superior performance regarding both accuracy and time efficiency in general multimodal image registration. In addition, dLDP also indicates the potential for clinical ultrasound guided intervention.


Cell-free biosynthesis of surfactin, a cyclic lipopeptide produced by Bacillus subtilis.
The lipopeptide antibiotic surfactin is a potent extracellular biosurfactant produced by various Bacillus subtilis strains. Biosynthesis of surfactin was studied in a cell-free system prepared from B. subtilis ATCC 21332 and OKB 105, which is a transformant producing surfactin in high yield [Nakano, M. M., Marahiel, M. A., & Zuber, P. (1988) J. Bacteriol. 170, 5662-5668]. Cell material was disintegrated by treatment with lysozyme and French press. A cell-free extract was prepared by ammonium sulfate fractionation, which catalyzed the formation of surfactin at the expense of ATP. Lipopeptide biosynthesis required the L-amino acid components of surfactin and D-3-hydroxytetradecanoyl-coenzyme A thioester. D-Leucine which is present in surfactin was not utilized but inhibited the biosynthetic process. The structure of surfactin, synthesized enzymatically in vitro, was confirmed by chromatographic comparison with the authentic compound and by amino acid analyses. An enzyme fraction was prepared by gel permeation chromatography which catalyzed ATP/pyrophosphate exchange reactions dependent on the component amino acids of surfactin. This enzyme fraction was capable of binding substrate amino acids covalently, probably via thioester linkages. The formation of these intermediates was inhibited by various thiol blocking reagents and phenylmethanesulfonyl fluoride. De novo synthesis of the lipopeptide was not observed with this partially purified enzyme fraction most likely due to the lack of an acyltransferase activity required for linking the beta-hydroxy fatty acid to the peptide moiety.


Relationship between altered structure and photochemistry in mutant reaction centers in which bacteriochlorophyll replaces the photoactive bacteriopheophytin.
Qy-excitation resonance Raman (RR) spectra are reported for two mutant reaction centers (RCs) from Rhodobacter capsulatus in which the photoactive bacteriopheophytin (BPhL) is replaced by a bacteriochlorophyll (BChl) molecule, designated beta. The pigment change in both mutants is induced via introduction of a histidine residue near the photoactive cofactor. In one mutant, L(M212)H, the histidine is positioned over the core of the cofactor and serves as an axial ligand to the Mg+2 ion. In the other mutant, F(L121)H/F(L97)V, the histidine is positioned over ring V of the cofactor, which is nominally too distant to permit bonding to the Mg+2 ion. The salient observations are as follows: (1) The beta cofactor in F(L121)H/F(L97)V RCs is a five-coordinate BChl molecule. However, there is no evidence for the formation of a Mg-His bond. This bond is either much weaker than in the L(M212)H RCs or completely absent, the latter implying coordination by an alternative ligand. The different axial ligation for beta in the F(L121)H/F(L97)V versus L(M212)H RCs in turn leads to different conformations of the BChl macrocycles. (2) The C9-keto group of beta in F(L121)H/F(L97)V RCs is free of hydrogen bonding interactions, unlike the L(M212)H RCs in which the C9-keto of beta is hydrogen bonded to Glu L104. The interactions between other peripheral substituents of beta and the protein are also different in the F(L121)H/F(L97)V RCs versus L(M212)H RCs. Accordingly, the position and orientation of beta in the protein is different in the two beta-containing RCs. Nonetheless, previous studies have shown that the primary electron transfer reactions are very similar in the two mutants but differ in significant respects compared to wild-type RCs. Collectively, these observations indicate that changes in the conformation of a photoactive tetrapyrrole macrocycle or its interactions with the protein do not necessarily lead to significantly perturbed photochemistry and do not underlie the altered primary events in beta-type RCs.


The purification and characterization of biological 6-sulphatoxymelatonin and comparison with synthetic 6-sulphatoxymelatonin.
We have purified the major metabolite of melatonin, 6-sulphatoxymelatonin, from urine and compared it to its synthetic counterpart. For preparation of the biological material, oral melatonin was administered to human volunteers and their urine extracted onto Amberlite XAD-2 resin to remove urea; the glucuronide metabolites of melatonin were removed by silica chromatography; and 6-sulphatoxymelatonin was separated from N-acetyl serotonin sulphate, the other sulphate metabolite of melatonin, by preparative thin-layer chromatography. Synthetic 6-sulphatoxymelatonin was produced by reacting 6-hydroxymelatonin with chlorosulphonic acid in dimethylformamide; the reaction mixture was purified on Florisil and preparative thin-layer chromatography was used to remove indolic by-products of the reaction. Elemental and X-ray microanalysis of the biological and synthetic products showed that classical methods used for their purification introduced inorganic impurities, such as silicon- and chlorine-containing compounds, which were not detectable by thin-layer chromatography, infrared spectroscopy, nuclear magnetic resonance spectroscopy, or gas chromatography-mass spectrometry. We introduced further purification steps to remove these inorganic impurities, monitoring the process using elemental and X-ray microanalysis. Extensive characterization of the resulting purified products showed that the biological and synthetic compounds were identical.


[A study on measles and rubella antibody level in 319 pairs of mothers and infants in Songjiang District of Shanghai].
Objective: To explore serum levels of measles and rubella IgG antibodies among mothers and infants. Methods: According to the inclusion and exclusion criteria, we selected 319 puerperae and their infants in maternal hospitals of Songjiang district November 2016 to February 2017, venous blood were collected and serum measles and rubella IgG antibodies were measured using ELISA. To study the correlation between the level of measles and rubella antibodies in infants and mothers' by using the Spearman's correlation analysis. Results: The age at delivery was (29.71±4.25) years old; and the gestational age at delivery was (39.06±1.30) weeks. The positive rate and protection rate of measles antibody in puerperae were 82.5% (243/319) and 43.3% (135/319), the GMC [M (QR)] was 655.74 (251.21-1 299.02) mIU/ml. The positive rate of rubella antibody in puerperae was 61.1% (195/319), the GMC [M (QR)] was 31.34 (11.65-73.61) IU/ml. The positive rate and protection rate of measles antibody in infants were 84.1% (270/321) and 46.1% (148/321), the GMC [M (QR)] was 665.07 (279.63-1 544.07) mIU/ml. The positive rate of rubella antibody in infants was 69.5% (223/321), the GMC [M (QR)] was 40.30 (16.12-98.48) IU/ml. There was statistical difference in measles (Z=-14.64, P<0.001) and rubella (Z=-8.66, P<0.001) antibody levels between mothers and infants. There was positive correlation in measles (r=0.76, P<0.001) and rubella (r=0.86, P<0.001) antibody level between mothers and infants. Conclusion: The maternal antibody of measles and rubella had a concentration effect. The level of measles and rubella antibodies in the infants was higher than that in the mothers' and increased with the increase of the level of measles and rubella antibodies in the mothers.


Office-based sutureless transconjunctival pars plana vitrectomy.
This is a preliminary report to describe our technique of office-based vitrectomy (OVIT) and to report the incidence of complications over a 6-year period. In a retrospective, noncomparative case series, OVIT was performed on 225 patients in four participating offices. Each patient was operated on with a 23-gauge vitreous cutter that the authors have developed. They have also developed a 23-gauge transconjunctival infusion needle device. Diagnoses included endophthalmitis, uveitis, intravitreal lens fragments, ghost cell glaucoma, and rhegmatogenous retinal detachment. The surgical goal was accomplished in all cases, but supplemental office procedures were required for two eyes, and a scleral buckle was necessary in one eye. There were 15 complications in 14 eyes: "fish-egg" gas bubbles (one eye), intraocular hemorrhage (nine eyes), choroidal detachment (two eyes), new retinal breaks (one eye), retinal detachment (one eye), and temporary elevation of intraocular pressure (one eye). The hemorrhages, choroidal detachments, and fish-egg bubbles all resolved spontaneously. Office-based sutureless transconjunctival pars plana vitrectomy, with infusion when needed, is an effective operation for selected diseases of the posterior segment. In a multicenter series of 225 eyes, there were 15 complications in 14 (6%) eyes. Two of the complications were successfully managed with additional office procedures; one was managed in the operating room; and 12 resolved spontaneously.


Leucine transport in cells isolated from cold-hardened and nonhardened winter rye.
The properties of the leucine transport systems of cells isolated from dark-grown cold-hardened and nonhardened winter rye (Secale cereale L. cv. Puma) epicotyls were remarkably similar. After 1 hour of incubation, leucine was accumulated in the cells 80- to 100-fold above that of the external medium, but the transported leucine was not metabolized. Approximately one-third of the accumulated leucine was present in the vacuole after 40 minutes of incubation. At 25 degrees C, efflux of leucine from the vacuole was 6 to 10 times slower than it was from the cytoplasm, while at 5 degrees C efflux from the cells was inhibited.The apparent K(m) and V(max) for leucine uptake for both types of cells were of the order of 20 to 60 micromolar and 0.5 to 1.3 nanomoles per minute per 10(6) cells. The pH and temperature optima for both types of cells were 5 and 25 degrees C, respectively. The leucine transport system for these cells was relatively specific for amino acids lacking either bulky or charged groups on the amino acid side chains.Arrhenius plots for leucine uptake by hardened and nonhardened cells showed discontinuities at 13 degrees C, and the energies of activation were similar. The results suggests that biochemical changes which occur in rye cells upon cold hardening did not result in an observable perturbation of the properties of the leucine transport system.


Hyperbranched Polysiloxanes Based on Polyhedral Oligomeric Silsesquioxane Cages with Ultra-High Molecular Weight and Structural Tuneability.
Hyperbranched siloxane-based polymers with ultra-high molecular weight were synthesized by the Piers⁻Rubinsztajn reaction between octakis(dimethylsiloxy) octasilsesquioxane with different dialkoxysilanes, using tris(pentafluorophenyl) borane as the catalyst. The origin of the high molecular weight is explained by the high reactivity of the catalyst and strain energy of isolated small molecule in which all eight silane groups close into rings on the sides of a single cubic cage. The structural tuneability was further demonstrated by use of methyl(3-chloropropyl)diethoxysilane, which generates a polymer with similar ultra-high molecular weight. Introduction of phosphonate groups through the chloropropyl sites later leads to functionalized polymers which can encapsulate various transition metal nanoparticles.


Use of aminoglycoside antibiotics in equine clinical practice; a questionnaire-based study of current use.
Veterinary use of the aminoglycoside antibiotics is under increasing scrutiny. This questionnaire-based study aimed to document the use of aminoglycosides with a particular focus on gentamicin. An online questionnaire was delivered to generalist equine veterinary surgeons and specialists in internal medicine to determine the perceived importance, frequency of use and routes of administration of the aminoglycoside antibiotics. A series of hypothetical scenarios were also evaluated regarding gentamicin. Data were compared to evaluate the impact of the level of specialisation on prescribing practices for different antibiotics using Chi-squared and Fischer's exact tests. Data were analysed from 111 responses. Gentamicin was commonly used empirically without culture and susceptibility testing. Generalists were more likely to use gentamicin only after susceptibility testing than specialists in a variety of clinical presentations including respiratory diseases, septic peritonitis, acute febrile diarrhoea, cellulitis and contaminated limb wounds (p < 0.01). Intravenous administration of gentamicin was most common, although inhaled and regional administration of gentamicin and amikacin were also described. Amikacin was most commonly used by intra-articular administration. Gentamicin was more likely to be used in high-risk procedures or contaminated surgeries (86% and 74%, respectively) compared with clean surgery (32%; p < 0.0001). Gentamicin was often used perioperatively in horses undergoing exploratory celiotomy and more commonly used in horses undergoing an enterotomy (90%) than without and enterotomy (79%; p = 0.04). Most respondents (86%) used gentamicin at a dose of 6.6 mg/kg in adults, with few changing their dosing strategies based on the presence of sepsis, although higher doses were more reported in foals (7-15 mg/kg) irrespective of the presence of sepsis. Aminoglycosides are widely used in equine practice and use outside current EU marketing authorisations is common. Stewardship of the aminoglycoside antibiotics could be enhanced in both generalists and specialists through the more frequent use of susceptibility testing, regional administration and dose adjustment, especially in foals.


Simultaneous determination of salbutamol, ractopamine, and clenbuterol in animal feeds by SPE and LC-MS.
A liquid chromatography-mass spectrometry (LC-MS) method for the simultaneous determination of salbutamol, ractopamine, and clenbuterol in commercial feeds was developed. Samples were extracted with phosphoric acid-methanol solution, and further clean-up was achieved with a C18 cation exchange mixed mode cartridge. Separation of analytes was developed on a C18 column with 0.01 M aqueous ammonium formate solution (pH 3.8)-acetonitrile by gradient program, and characterized by LC-MS on a quadrupole detector, in electrospray positive ion mode. This method provides average recoveries for salbutamol, ractopamine, and clenbuterol of 83-110% and coefficients of variation of 1.5-11% in feeds spiked in the range of 0.5-500 mg/kg. The limits of detection and quantification in feeds were 0.01 mg/kg and 0.05 mg/kg, respectively. Such limits are well below the dose of 2-25 mg/kg feed proposed as effective.


Cytokines and soluble cytokine receptors in pleural effusions from septic and nonseptic patients.
The balance between proinflammatory cytokines and their inhibitors has rarely been investigated in pleural effusions of nonmalignant or noninfectious origin. To evaluate the impact of a lung and/or intrathoracic infection in such a circumstance, we compared the levels of proinflammatory cytokines (interleukin-8 [IL-8]); tumor necrosis factor-alpha (TNF-alpha); the cytokine antagonists and inhibitors (IL-1 receptor antagonist [IL-1ra]) and soluble TNF receptors Types I and II (sTNFRI, sTNFRII); and antiinflammatory cytokines (transforming growth factor-beta [TGF-beta]) in pleural effusion and plasma from septic (n = 15) and nonseptic (n = 9) patients. In addition, we analyzed the levels of IL-6 and its soluble receptor (sIL-6R). Bronchoalveolar lavage fluids (BALFs) were also studied in a few septic patients. High and nonsignificantly different levels of cytokines and inhibitors were detected in both groups of patients. The levels of IL-6 and sTNFRI and sTNFRII in pleural effusion were higher than in plasma, whereas the levels of IL-1ra and sIL-6R were higher in plasma. The levels of sIL-6R influenced the bioactivity of IL-6. There was no correlation between the levels of cytokines in plasma and in pleural effusion. In contrast, a significant correlation was observed for the soluble receptors sIL-6R (r = 0.67, p < 0.001), sTNFRI (r = 0.76, p < 0.001) and sTNFRII (r = 0.66, p = 0.001). Furthermore, a high correlation was found between the levels of both forms of sTNFRs in plasma (r = 0.95, p < 0.001) and in pleural effusion (r = 0.79, p < 0.001). In addition, a correlation was observed between the levels of TGF-beta in pleural effusion and in BALF. The highest levels of some markers in plasma and of others in pleura argue in favor of both a systemic and a compartmentalized response, independently of the presence of infection. Because cytokines can be trapped by the surrounding cells in their environment, measurable levels of cytokines in biologic fluids represent the "tip of the iceberg," which is not the case for soluble receptors. The correlations of these latter markers between plasma and pleura strongly suggest that exchanges between both compartments can occur in both directions.


Translation and validation of the Chinese ABCD risk questionnaire to evaluate adults' awareness and knowledge of the risks of cardiovascular diseases.
Assessment of health beliefs and risk perception is a critical means to prevent coronary heart disease, but there are few such studies on assessment in the Chinese population. Given the demonstrated value and widespread use of the Attitudes and Beliefs about Cardiovascular Disease Risk Questionnaire (ABCD), this study was designed to translate it into Chinese, and to evaluate its reliability and validity in a Chinese population. The Chinese version of the ABCD was created using the Beaton translation model, which included forward and backward translation. The reliability and construct validity of the Chinese ABCD were examined in a sample of 353 adults who participated in the public welfare projects of the Chinese National Center for Cardiovascular Diseases in Guilin city, Guangxi. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed to examine the factor structure of the Chinse ABCD. The internal consistency of the questionnaire was assessed using Cronbach's α and corrected item-total correlations. We deleted item 7 in the knowledge dimension of the Chinese ABCD and added two items about smoking and sleep knowledge, while retaining 25 of the original items, so that it finally included 27 items. The correlations were .20-.90; the correlations between each item and the total score of the ABCD were .34-.86; and the item-level Content Validity Index (I-CVI) was .86-1.00. The results of the EFA showed that all items were close to .40, and the cumulative variance contribution rate was 63.88%. The model fit was acceptable (χ2 = 698.79, df = 243, χ2/df = 2.87, P < 0.001, SRMR = 0.06, RMSEA = 0.05, CFI = 0.96, and TLI = 0.94) according to the CFA. The Cronbach' s α of the entire questionnaire was .86, and the α of each of dimension was .65, .90, .88, and .78. The split-half reliability of the entire the ABCD was .67, and the test-retest reliability was .97 (P < 0.05). The questionnaire had good reliability and validity and was associated with sociodemographic and health-related characteristics (smoking and Body Mass Index). The Chinese version of the ABCD has good reliability and validity, and provides a reliable assessment tool for measuring public health beliefs about the risk of cardiovascular disease, promoting the primary prevention of coronary heart disease.


Effect of parenteral immunization on the intestinal immune response to Salmonella typhi Ty21a.
The effects of parenteral administration of a killed typhoid vaccine on the intestinal immune response to live orally administered Salmonella typhi Ty21a in human subjects was evaluated. Priming with parenteral vaccination neither enhanced nor suppressed the subsequent specific serum and intestinal immunoglobulin A (IgA) immune responses to a booster course of live oral vaccine. Neither a single oral dose of live vaccine nor a single dose of parenteral vaccine had any measurable booster effect on the observed primary intestinal IgA response to the live oral vaccine. Two booster doses of subcutaneously administered killed typhoid vaccine did result in a significant increase in the specific intestinal IgA antibody in those subjects primed with the oral live vaccine. This response was comparable in magnitude to the primary intestinal response. No evidence of this response could be found in serum IgA, although nonsignificant rises in serum IgG were evident. Previous parenteral priming had no effect on secondary immune responses to a live oral vaccine in humans. Serum immune responses were generally found to be of little value as indicators of local intestinal immunity. This study confirmed that parenteral vaccination was only able to induce an intestinal immune response following priming with live, orally administered organisms and that multiple parenteral booster doses were necessary to induce a measurable effect on intestinal immune responses.


Schmidingerothrix salinarum nov. spec. is the molecular sister of the large oxytrichid clade (ciliophora, hypotricha).
In 2012, Foissner described a curious hypotrich: Schmidingerothrix extraordinaria. This ciliate, which he discovered in hypersaline soils (~100‰) from Namibia, had a frayed buccal lip, three-rowed adoral membranelles, only one frontal cirrus, and a miniaturized first frontal membranelle, while a paroral membrane, dorsal bristle rows and buccal, transverse and caudal cirri were absent. All opisthe structures developed de novo, while parental structures were involved in the proter. When Foissner's study became available, we discovered a similar species in a Portuguese solar saltern, differing from S. extraordinaria mainly by the number of frontoventral cirral rows (3 vs. 1). Furthermore, parental structures were involved in the ontogenesis of both proter and opisthe. The small subunit (SSU) rDNA shows Schmidingerothrix as sister of a large clade containing most classical oxytrichids (e.g. Sterkiella, Oxytricha, Steinia) and many related taxa (e.g. Pattersoniella, Bistichella, Uroleptus). This clade shows a bifurcation named "Oxytricha subclade" and "Uroleptus subclade". Foissner () interpreted the peculiarities of Schmidingerothrix as a reduction caused by the extreme habitat. However, the molecular data do not exclude that Schmidingerothrix presents an ancient state. A morphology-based scheme is presented, showing how the subclades might have evolved from a Schmidingerothrix-like ancestor.


Computing microRNA-gene interaction networks in pan-cancer using miRDriver.
DNA copy number aberrated regions in cancer are known to harbor cancer driver genes and the short non-coding RNA molecules, i.e., microRNAs. In this study, we integrated the multi-omics datasets such as copy number aberration, DNA methylation, gene and microRNA expression to identify the signature microRNA-gene associations from frequently aberrated DNA regions across pan-cancer utilizing a LASSO-based regression approach. We studied 7294 patient samples associated with eighteen different cancer types from The Cancer Genome Atlas (TCGA) database and identified several cancer-specific and common microRNA-gene interactions enriched in experimentally validated microRNA-target interactions. We highlighted several oncogenic and tumor suppressor microRNAs that were cancer-specific and common in several cancer types. Our method substantially outperformed the five state-of-art methods in selecting significantly known microRNA-gene interactions in multiple cancer types. Several microRNAs and genes were found to be associated with tumor survival and progression. Selected target genes were found to be significantly enriched in cancer-related pathways, cancer hallmark and Gene Ontology (GO) terms. Furthermore, subtype-specific potential gene signatures were discovered in multiple cancer types.


Effects of All-Trans Retinoic Acid on the Optimization of Synovial Explant Induced by Tumor Necrosis Factor Alpha.
Current studies focused on the effects of all-trans-retinoic acid (ATRA) on synovial explants from rats with rheumatoid arthritis (RA) induced by lipopolysaccharides (LPS). In our study, synovial membranes were extracted aseptically from the quadriceps femoris of the knee joint of rats, and then incubated in medium containing 10% neonate bovine serum for 24 h adaptive culture. We first measured variations of correlation factors in synovium at 24, 48, 72, 96 and 120 h in control medium or in medium containing 20 ng/mL tumor necrosis factor alpha (TNF-α) (TNF-α-experiment). Then, we investigated the synovium exposed to three ATRA concentrations after 48 h incubation (ATRA-experiment). The effects of ATRA on synovitis were evaluated by observing the expression of inflammatory cytokines, angiogenic factors and the production of proteases in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway and apoptosis and autophagy. In TNF-α-experiment, the secretion of nitric oxide (NO), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) increased significantly after TNF-α stimulation without pathological damage to the synovium. Hence, we successfully obtained the synovial explants model, which had longer inflammatory response time. In the ATRA-experiment, ATRA suppressed the secretion of IL-6 and NO, downregulated the NF-κB P65 and Bcl-2, increased levels of autophagy marker protein LC3, but different doses of ATRA showed inconsistent regulatory effects on VEGF and MMP-9. In short, ATRA inhibited TNF-α induced synovitis by the regulation of inflammatory cytokines and inhibiting NF-κB signal transduction and potentially promoting autophagy, apoptosis and angiogenesis, displaying its role in alleviating synovial inflammation in patients with RA.


Contemporary femoral designs in total knee arthroplasty: effects on the patello-femoral congruence.
The objective of this study was to evaluate the radiological and clinical correlations between implant design and patellar positioning in patients who underwent TKA utilizing femoral implants with modern designs. Thirty consecutive PFC PS Sigma TKAs, characterized by a new prolonged anterior flange and a "smoother" trochlea, were prospectively reviewed. All patellae were replaced. All patients were evaluated pre-operatively and prospectively at two years follow-up both clinically according to the Knee Society score as well as radiographically. This included computed tomography (CT); patellar tilt, patellar conformity angle, patellar lateralization, and femoral component external-rotation in relation to the clinical trans-epicondylar axis. Average patellar tilt at follow-up was 3° (±7.5°) with respect to a pre-operative 18.5° (±8.5°). Average patellar congruence angle at follow-up was -3° (range, -11° to +9°) with respect to a pre-operative 10.3° (range, + 1.5° to 25.5°). Average lateralization index at follow-up was 2.7 mm (range, -3.4 mm to +7.1 mm) with respect to a pre-operative 12.2 mm (± 4.8 mm). Femoral component positioning related to the trans-epicondylar axis showed an external rotation of 2.80° (± 2.10°) at follow-up with respect to 5.7° (± 1.80°). Clinically, two (6.6%) patients reported patello-femoral complications related to imperfections in the surgical technique more than the implant's design. This study highlighted that modern femoral designs in TKA allow for a correct reproducibility of a normal patello-femoral conformity. Strict surgical principles are paramount to avoid patello-femoral complications even when modern implants are used.


Positivity explains how COVID-19 perceived risk increases death distress and reduces happiness.
The novel coronavirus (COVID-19) pandemic has produced an unprecedented impact on all aspects of life, including mental outcomes like death distress. This study examined the mediating effect of positivity on the association between COVID-19 related perceived risk, death distress, and happiness. Participants were 3109 Turkish adults (Mean age = 38.64 ± 10.40) who completed online measures of perceived risk, positivity, death distress, and happiness during the pandemic. Results showed that perceived risk had a significant direct effect on positivity, death distress, and happiness. Positivity had a significant direct effect on death distress and happiness. Mediation analysis indicated that positivity mediated the effect of perceived risk on death distress and happiness. Results suggest that positivity is an important aspect of developing strength-based preventions and interventions aiming to reduce psychological distress and improve happiness.


An azophenine radical-bridged Fe2 single-molecule magnet with record magnetic exchange coupling.
One-electron reduction of the complex [(TPyA)2Fe(II)2((NPh)L(2-))](2+) (TPyA = tris(2-pyridylmethyl)amine, (NPh)LH2 = azophenine = N,N',N",N'''-tetraphenyl-2,5-diamino-1,4-diiminobenzoquinone) affords the complex [(TPyA)2Fe(II)2((NPh)L(3-•))](+). X-ray diffraction and Mössbauer spectroscopy confirm that the reduction occurs on (NPh)L(2-) to give an S = 1/2 radical bridging ligand. Dc magnetic susceptibility measurements demonstrate the presence of extremely strong direct antiferromagnetic exchange between S = 2 Fe(II) centers and (NPh)L(3-•) in the reduced complex, giving an S = 7/2 ground state with an estimated coupling constant magnitude of |J| ≥ 900 cm(-1). Mössbauer spectroscopy and ac magnetic susceptibility reveal that this complex behaves as a single-molecule magnet with a spin relaxation barrier of U(eff) = 50(1) cm(-1). To our knowledge, this complex exhibits by far the strongest magnetic exchange coupling ever to be observed in a single-molecule magnet.


Behaviors in self-prevention of malaria among mobile population in east Thailand.
The study investigated preventive behaviors among mobile villagers in Chanthaburi and Trat Provinces where the slide positive rates (SPR) of malaria in 1987 were 10.3 and 11.1%, respectively. The study was conducted in four villages namely Wang Thong, Khao Thong in Chanthaburi, and Manow and Khow in Trat by using a cross-sectional survey. Household and in-depth interviews with the movers were done together with field observations. The sizes of the villages were 52, 180, 184 and 209 households and the movement rates were 23.1, 12.2, 37.5 and 28.7%, respectively. The population involved in short term migration was 729 villagers living in 153 households or 23.7% of the total. Malaria prevalence rates in the four villages were 7.5%, 5.9%, 7.3% and 2.2%, respectively. The results indicate that the mobile population had a moderate 40% rating score of knowledge about malaria. Apparently, the rating score of preventive behaviors of the disease appeared to be as small as 20%. After six months of field investigations, 1,083 thick blood smears collected from the mobile population, there were 657 episodes (60.7%) of malaria that could be categorized with age specific prevalence of 60.3% in 19-29 years, 80.8% in 30-39 years, 54.8% in 40-49 years, 38.6% in 50-59 years and 35.7% in 60 years and over. Villagers aged between 30-39 years with frequent movement into the forest had the highest impact of malaria risk. Moderate levels of knowledge and attitude scores did not appear to enable the people to protect themselves against malaria.


Chemoavailability of Organic Electrophiles: Impact of Hydrophobicity and Reactivity on Their Aquatic Excess Toxicity.
Organic electrophiles have been recognized as important components of the exposome that can be characterized as cumulative totality of exposure in the organism in response to environmental perturbation. For such compounds, chemical reactivity may contribute significantly to the toxicological profile through covalent attacks at nucleophilic sites of peptides such as glutathione (GSH), proteins, lipid components, and the DNA and RNA. Employing a Michael acceptor set of 58 α,β-unsaturated carbonyls with 15 ketones, 18 aldehydes, and 25 esters, the hydrophobicity and reactivity contributions to their toxicity enhancement Te over baseline narcosis with the ciliates Tetrahymena pyriformis is analyzed through a conceptual model, featuring toxicokinetic phase transfer steps and the reactive molecular initiating event (MIE) at endogenous target sites exposed to water-rich or water-poor compartments. To this end, hydrophobicity was quantified by the octanol/water partition coefficient, Kow, electrophilic reactivity through second-order rate constants of reaction with GSH in a kinetic chemoassay, kGSH, and Te as the ratio of narcosis-level vs experimental concentration yielding 50% growth inhibition of the ciliates within 48 h of exposure. The observed decrease of log Te with increasing log Kow can be traced back to a rate-determining impact of the toxicant transfer from the membrane to the intracellular cytosol. Moreover, the recently introduced concept of chemoavailability is shown to enable, from knowledge of log Kow and log kGSH alone, a screening-level discrimination between reactive and hydrophobic MIEs triggering predominantly alone or in parallel respective adverse outcome pathways (AOPs) including the diffusion-control limit of reactive MIE saturation. As such, chemoavailability may aid in evaluating prevalent MIEs expected for a given organic electrophile and in assessing its toxicological profile within AOP schemes addressing aquatic toxicity.


Structural study of the N-linked oligosaccharides of hepatocyte growth factor by two-dimensional sugar mapping.
The structures of the N-linked oligosaccharides on recombinant human hepatocyte growth factor (rh-HGF) expressed by Chinese hamster ovary (CHO) cells were studied by two-dimensional sugar mapping. The oligosaccharides released from the glycopeptides by peptide: N-glycosidase F (PNGase F) treatment were tagged with 2-aminopyridine at the reducing ends. The alpha-chain was linked by biantennary, triantennary, and tetraantennary oligosaccharides, but the dominant oligosaccharides linking the beta-chain were biantennary (> 85%). There was no significant difference in oligosaccharide structures between the two glycosylation sites on each chain, that is, Asn263 and Asn371 on the alpha-chain, and Asn535 and Asn622 on the beta-chain. The linkage of sialic acid to the non-reducing terminal galactose was identified as NeuAc alpha(2-3) by 1H-NMR spectrometry. The structures of the N-linked oligosaccharides from rat HGF were also studied. Triantennary oligosaccharides were obtained from the alpha-chain and a biantennary oligosaccharide was obtained from the beta-chain. This result indicates that the alpha-chain is also linked by higher branched oligosaccharides than the beta-chain in rat HGF.


Simple analog correlator.
An analog correlator has been constructed using a delay unit which is realized by simulation of the sixth-order Pade approximated result of exp(-jomegatau) where j= radical-1, omega the angular frequency of the signals of concern, and tau the delay in seconds. Several sinusoidal signals and a noise spectrum have been autocorrelated with this correlator; also, it has been applied to determine the impulse response of an RC low-pass filter. Results are in good agreement with theoretical predictions. This correlator has been used to study low- frequency signals in the region 1-50 kHz.


Successful alternatives to alternate site testing. Use of a pneumatic tube system to the central laboratory.
We evaluated the use of several modes of alternate site versus central laboratory testing in our hospital to provide improved processing of stat specimens from the Emergency Department and the Operating Room. Using the principle of parallel processing for sample analysis, coupled with installation of a computerized pneumatic tube specimen delivery system, we provided improved turnaround time, a larger test menu, and 24-hour-a-day service from the central laboratory. As a result, the satellite laboratory in the Emergency Department was closed and 16 full-time equivalent positions were saved in the hospital. A separate tube zone was established for the Operating Room, and a critical care whole-blood test unit was established in the central laboratory, providing 7-minute turnaround time for blood gases, electrolytes, and glucose. Testing in the Operating Room by nonlaboratory personnel was discontinued.


Selective macrophage depletion in the liver does not prevent the development of the sick euthyroid syndrome in the mouse.
A decreased serum triiodothyronine (T3) level is one of the main characteristics of the sick euthyroid syndrome, caused mainly by a decreased 5'-deiodination of thyroxine (T4) in the liver. Cytokines have been implicated in the pathogenesis of the changes in thyroid hormone metabolism during illness. We therefore investigated the role of cytokines produced by the liver macrophages (Kupffer cells) in the development of the sick euthyroid syndrome, which was induced in mice by a single injection of bacterial endotoxin (lipopolysaccharide) or by 24-h starvation. Experiments were carried out with or without previous selective depletion of liver macrophages by intravenous administration of liposome-encapsulated dichloromethylene diphosphonate. Relative to saline-injected pair-fed controls, the administration of lipopolysaccharide caused a decrease of serum T3 and T4 and liver 5'-deiodinase mRNA. Selective depletion of liver macrophages, did not affect these changes. Starvation for 24h decreased serum T3 and T4, associated with a slight decrease of liver 5'-deiodinase mRNA. There were no differences between macrophage-depleted and non-depleted animals in this respect. In summary, selective depletion of liver macrophages did not affect the decrease in serum T3, T4 or liver 5'-deiodinase mRNA induced by lipopolysaccharide or 24-h starvation in mice. We conclude that cytokines produced by Kupffer cells are not involved in the pathogenesis of the sick euthyroid syndrome in this experimental model.


Regulation of vasopressin messenger RNA levels in the small cell lung carcinoma cell line GLC-8: interactions between glucocorticoids and second messengers.
The role of glucocorticoids and second messenger systems in the regulation of the vasopressin (VP) gene was studied in the human small cell lung carcinoma cell line GLC-8. Small cell lung carcinoma GLC-8 cells express VP mRNA and contain both glucocorticoid and mineralocorticoid receptors. Treatment with the synthetic glucocorticoid dexamethasone when added alone at 10(-8) M had no effect on the VP mRNA level and decreased the level by 30% at 10(-6) M. However, the effect of dexamethasone changed to positive when cells were simultaneously treated with cAMP-enhancing agents. VP mRNA levels, which were elevated by 1.5- to 2-fold by the cAMP-enhancing agents alone, increased a further 1.5- to 3-fold by dexamethasone. Thus, the combined effect of dexamethasone and cAMP stimulation was a 3- to 7.5-fold increase in VP mRNA levels. Long term treatment with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) reduced the VP mRNA level by 75%. The TPA-suppressed VP mRNA levels could be up-regulated about 6-fold by simultaneous treatment with 8-bromo-cAMP. Dexamethasone did not alter the TPA-suppressed VP mRNA levels. These results indicate that both cAMP and protein kinase-C pathways as well as glucocorticoid receptors are involved in the regulation of VP mRNA levels and that these factors interact. This leads to a negative or positive response of VP gene expression to glucocorticoids in a state-dependent manner. The interactions may be of significance in a physiological context and relate to the different regulation of VP-expressing systems in the brain.


Long-term prophylaxis of hereditary angioedema with a pasteurized C1 inhibitor concentrate.
Hereditary angioedema (HAE) is a relatively rare genetic disorder caused by a deficiency of C1 esterase inhibitor (C1-INH). Common clinical presentations are abdominal pain and localized edema of the skin, with laryngeal edema being potentially life-threatening. Replacement therapy with C1-INH concentrate is recommended for treatment of acute HAE attacks and results in rapid resolution of symptoms. C1-INH concentrate can also be used for prophylaxis of HAE and is recommended in cases where standard prophylactic agents are ineffective or not tolerated. This case study describes the use of C1-INH concentrate as a home therapy for on-demand and prophylactic self-administration in a patient with HAE. This treatment approach was well tolerated and effective, leading to a dramatic improvement in symptoms and improved quality of life.


Targeting heme oxygenase: therapeutic implications for diseases of the cardiovascular system.
Heme oxygenase (HO) is important in attenuating the overall production of reactive oxygen species through its ability to degrade heme and to produce carbon monoxide, biliverdin/bilirubin, and release of free iron. Excess free heme catalyzes the formation of reactive oxygen species, which leads to endothelial cell (EC) dysfunction as seen in numerous pathologic vascular conditions including systemic hypertension and diabetes, as well as in ischemia/reperfusion injury.The up-regulation of HO-1 can be achieved through the use of pharmaceutical agents such as metalloporphyrins and statins. In addition, atrial natriuretic peptide and nitric oxide donors are important modulators of the heme-HO system, either through induction of HO-1 or the increased biologic activity of its products. Gene therapy and gene transfer, including site- and organ-specific targeted gene transfer have become powerful tools for studying the potential role of the 2 isoforms of HO, HO-1/HO-2, in the treatment of cardiovascular disease, as well as diabetes. HO-1 induction by pharmacological agents or the in vitro gene transfer of human HO-1 into ECs increases cell cycle progression and attenuates angiotensin II, tumor necrosis factor-alpha, and heme-mediated DNA damage; administration in vivo corrects blood pressure elevation after angiotensin II exposure. Delivery of human HO-1 to hyperglycemic rats significantly lowers superoxide levels and prevents EC damage and sloughing of vascular EC into the circulation. In addition, administration of human HO-1 to rats in advance of ischemia/reperfusion injury considerably reduces tissue damage.The ability to up-regulate HO-1 either through pharmacological means or through the use of gene therapy may offer therapeutic strategies for the prevention of cardiovascular disease in the future. This review discusses the implications of HO-1 delivery during the early stages of cardiovascular system injury or in early vascular pathology, and suggests that pharmacological agents that regulate HO activity or HO-1 gene delivery itself may become powerful tools for preventing the onset or progression of various cardiovascular diseases.


Clinical heterogeneity of dopa-responsive dystonia: PET observations.
Parkinsonism without dystonia has been reported in several older members of families with DRD. This raises the question whether such patients represent a variant in the clinical picture of DRD, or a separate disease, IP. We employed 6-FD PET to study the nigrostriatal dopaminergic function in a woman with typical DRD and two of her relatives with late-onset parkinsonism. These two had an excellent and prolonged therapeutic response to small doses of L-DOPA, without complications. We found that the dystonic patient and the women with "benign" parkinsonism had normal striatal 6-FD uptake. In conjunction with other clinical evidence, our PET study indicates that the biochemical lesion in these members may be "proximal" to dopa decarboxylase, as is suggested in DRD patients. We conclude that the adult-onset parkinsonism in DRD families is due to the same pathophysiological mechanism as the childhood-onset dystonia in the disease. DRD may display substantial clinical heterogeneity depending on the age of onset.


Inhibition of p38 MAPK by glucocorticoids via induction of MAPK phosphatase-1 enhances nontypeable Haemophilus influenzae-induced expression of toll-like receptor 2.
Despite the importance of glucocorticoids in suppressing immune and inflammatory responses, their role in enhancing host immune and defense response against invading bacteria is poorly understood. We have demonstrated recently that glucocorticoids synergistically enhance nontypeable Haemophilus influenzae (NTHi)-induced expression of Toll-like receptor 2 (TLR2), an important TLR family member that has been shown to play a critical role in host immune and defense response. However, the molecular mechanisms underlying the glucocorticoid-mediated enhancement of TLR2 induction still remain unknown. Here we show that glucocorticoids synergistically enhance NTHi-induced TLR2 expression via specific up-regulation of the MAPK phosphatase-1 (MKP-1) that, in turn, leads to dephosphorylation and inactivation of p38 MAPK, the negative regulator for TLR2 expression. Moreover, increased expression of TLR2 in epithelial cells greatly enhances the NTHi-induced expression of several key cytokines, including tumor necrosis factor-alpha and interleukins 1beta and 8, thereby contributing significantly to host immune and defense response. These studies may bring new insights into the novel role of glucocorticoids in orchestrating and optimizing host immune and defense responses during bacterial infections and enhance our understanding of the signaling mechanisms underlying the glucocorticoid-mediated attenuation of MAPKs.