Contrasting female mate preferences for red coloration in a fish.
Understanding how animals select their mates requires knowing the factors that shape mate preferences. Recent theoretical and empirical considerations suggest that female mating status can influence the degree to which a female engages in mate choice, with virgin females predicted to be less choosy than mated females. In this study, we investigated mate choice in both virgin and mated females in the pygmy halfbeak Dermogenys collettei. Halfbeaks are small, live-bearing, internally fertilizing freshwater fish that live in mixed-sex groups where females have ample opportunity to engage in mate choice. Using a dichotomous choice assay, we quantified and contrasted in virgin and mated females mate preferences for differences in male body size, beak size, and area of yellow and red coloration. We also examined how mating status influenced the amount of time a female associated with the first male encountered and the relative amount of time a female associated with each male. We demonstrate that mate preferences of female halfbeaks are driven primarily by the size of red coloration present on males. Females showed contrasting preferences based on mating status, with virgin females preferentially associating with drab males whereas mated females preferentially associate with males possessing large areas of red. Contrary to expectations, female mating status did not influence how females associate with the first males encountered or how females biased their association time among males. Although the precise drivers of these effects need further studying, our finding highlights a possible explanation for how variation in male ornamentation can be maintained.


Zeta potential of mica covered by colloid particles: a streaming potential study.
The streaming potential of mica covered by monodisperse latex particles was measured using the parallel-plate channel, four-electrode cell. The zeta potential of latex bearing amidine charged groups was regulated by the addition of NaCl (10(-4)-10(-2) M) and MgCl(2) (10(-4)-10(-2) M) at a constant pH 5.5 and by the change in pH (4-12) at 10(-2) M NaCl. The size of the latex particles, determined by dynamic light scattering, varied between 502 and 540 nm for the above electrolyte concentration range. Mica sheets have been covered with latex particles under diffusion transport conditions. The latex coverage was regulated by the bulk suspension concentration in the channel and the deposition time. The coverage was determined, with a relative precision of 2%, by the direct enumeration of particles by optical microscopy and AFM. The streaming potential of mica was then determined for a broad range of particle coverage 0 < theta < 0.5, the particle-to-substrate zeta potential ratio zeta(p)/zeta(i), and 8.8 < kappa a < 143 (thin double-layer limit). These experimental data confirmed that the streaming potential of covered surfaces is well reflected by the theoretical approach formulated in ref 32. It was also shown experimentally that variations in the substrate streaming potential with particle coverage for theta < 0.3 and zeta(p)/zeta(i) < 0 are characterized by a large slope, which enables the precise detection of particles attached to interfaces. However, measurements at high coverage and various pH values revealed that the apparent zeta potential of covered surfaces is 1/2(1/2) smaller than the bulk zeta potential of particles (in absolute terms). This is valid for arbitrary zeta potentials of substrates and particles, including the case of negative particles on negatively charged substrates that mimics rough surfaces. Therefore, it was concluded that the streaming potential method can serve as an efficient tool for determining bulk zeta potentials of colloids and bioparticles.


Aneurysmal subarachnoid hemorrhage and severe, catheter-induced vasospasm associated with excessive consumption of a caffeinated energy drink.
Excessive consumption of over-the-counter stimulants is associated with coronary vasospasm, thrombotic complications, and sudden cardiac death. Their effects on cerebrovascular physiology are not yet described in the neurointerventional literature. Patients are increasingly exposed to high levels of these vasoactive substances in the form of caffeinated energy drinks and specialty coffees. We report a case of aneurysmal subarachnoid hemorrhage (SAH) and severe, catheter-induced vasospasm during attempted endovascular repair of a ruptured anterior communicating artery (AComA) aneurysm in the setting of excessive energy drink consumption. We review the literature and alert clinicians to this potentially serious complication.


Hydrogen Production by Steam Reforming of Liquefied Natural Gas (LNG) Over Nickel-Phosphorus-Alumina Xerogel Catalyst Prepared by a Carbon-Templating Epoxide-Driven Sol-Gel Method.
A nickel-phosphorus-alumina xerogel catalyst was prepared by a carbon-templating epoxide-driven sol-gel method (denoted as CNPA catalyst), and it was applied to the hydrogen production by steam reforming of liquefied natural gas (LNG). For comparison, a nickel-phosphorus-alumina xerogel catalyst was also prepared by a similar method in the absence of carbon template (denoted as NPA catalyst). The effect of carbon template addition on the physicochemical properties and catalytic activities of the catalysts in the steam reforming of LNG was investigated. Both CNPA and NPA catalysts showed excellent textural properties with well-developed mesoporous structure. However, CNPA catalyst retained a more reducible nickel aluminate phase than NPA catalyst. XRD analysis of the reduced CNPA and NPA catalysts revealed that nickel sintering on the CNPA catalyst was suppressed compared to that on the NPA catalyst. From H2-TPD and CH4-TPD measurements of the reduced CNPA and NPA catalysts, it was also revealed that CNPA catalyst with large amount of hydrogen uptake and strong hydrogen-binding sites showed larger amount of methane adsorption than NPA catalyst. In the hydrogen production by steam reforming of LNG, CNPA catalyst with large methane adsorption capacity showed a better catalytic activity than NPA catalyst.


Synergistic Interactions in Sequential Process Doping of Polymer/Single-Walled Carbon Nanotube Nanocomposites for Enhanced n-Type Thermoelectric Performance.
This study focuses on the fabrication of nanocomposite thermoelectric devices by blending either a naphthalene-diimide (NDI)-based conjugated polymer (NDI-T1 or NDI-T2), or an isoindigo (IID)-based conjugated polymer (IID-T2), with single-walled carbon nanotubes (SWCNTs). This is followed by sequential process doping method with the small molecule 4-(2,3-dihydro-1,3-dimethyl-1H-benzimidazol-2-yl)-N,N-dimethylbenzenamine (N-DMBI) to provide the nanocomposite with n-type thermoelectric properties. Experiments in which the concentrations of the N-DMBI dopant are varied demonstrate the successful conversion of all three polymer/SWCNT nanocomposites from p-type to n-type behavior. Comprehensive spectroscopic, microstructural, and morphological analyses of the pristine polymers and the various N-DMBI-doped polymer/SWCNT nanocomposites are performed in order to gain insights into the effects of various interactions between the polymers and SWCNTs on the doping outcomes. Among the obtained nanocomposites, the NDI-T1/SWCNT exhibits the highest n-type Seebeck coefficient and power factor of -57.7 µV K-1 and 240.6 µW m-1 K-2 , respectively. However, because the undoped NDI-T2/SWCNT exhibits a slightly higher p-type performance, an integral p-n thermoelectric generator is fabricated using the doped and undoped NDI-T2/SWCNT nanocomposite. This device is shown to provide an output power of 27.2 nW at a temperature difference of 20 K.


LPA4-Mediated Vascular Network Formation Increases the Efficacy of Anti-PD-1 Therapy against Brain Tumors.
: The structure and function of tumor blood vessels profoundly affects the tumor microenvironment. Signals mediated through the lysophosphatidic acid receptor 4 (LPA4) promote vascular network formation to restore normal vascular barrier function in subcutaneous tumors and thus improve drug delivery. However, the characteristics of the vasculature vary by organ and tumor types, and how drug delivery and leukocyte trafficking are affected by modification of vascular function by LPA in different cancers is unclear. Here, we show that LPA4 activation promotes the formation of fine vascular structures in brain tumors. RhoA/ROCK signaling contributed to LPA-induced endothelial cell-cell adhesion, and RhoA/ROCK activity following LPA4 stimulation regulated expression of VCAM-1. This resulted in increased lymphocyte infiltration into the tumor. LPA improved delivery of exogenous IgG into brain tumors and enhanced the anticancer effect of anti-programmed cell death-1 antibody therapy. These results indicate the effects of LPA on vascular structure and function apply not only to chemotherapy but also to immunotherapy. SIGNIFICANCE: These findings demonstrate that lysophosphatidic acid, a lipid mediator, promotes development of a fine capillary network in brain tumors by inducing tightening of endothelial cell-to-cell adhesion, facilitating improved drug delivery, and lymphocyte penetration.


Transition energies of benzoquinone anions are immune to symmetry breaking by a single water molecule.
p-Benzoquinone is the prototypical member of the quinone class of molecules with a basic functionality relevant for the primary reactions of photosynthesis. As electronically excited quinone anions are formed in near-resonant electron transfer, key issues are how the local environment affects excited-state energy levels and deexcitation times. The former we address here with action spectroscopy of mass-selected bare radical anions (pBQ(-)) and one-water pBQ(-)·H2O complexes, isolated in vacuo. The complex represents a precursor for internal proton transfer to form the semiquinone free radical, the first chemical product in the light-driven electron transport chain. Both ions display bands in the visible and ultraviolet with, importantly, almost identical maxima. Despite localizing negative charge, thereby breaking the high orbital symmetries, water is surprisingly innocent. This finding implies that natural fluctuations in the quinone microenvironment cause only minor variations in excited-state energies and thus electron-transfer rates. Hence quinones are robust participants in electron transport.


Two different mirror neuron networks: The sensorimotor (hand) and limbic (face) pathways.
The vast majority of functional studies investigating mirror neurons (MNs) explored their properties in relation to hand actions, and very few investigated how MNs respond to mouth actions or communicative gestures. Since hand and mouth MNs were recorded in two partially overlapping sectors of the ventral precentral cortex of the macaque monkey, there is a general assumption that they share a same neuroanatomical network, with the parietal cortex as a main source of visual information. In the current review, we challenge this perspective and describe the connectivity pattern of mouth MN sector. The mouth MNs F5/opercular region is connected with premotor, parietal areas mostly related to the somatosensory and motor representation of the face/mouth, and with area PrCO, involved in processing gustatory and somatosensory intraoral input. Unlike hand MNs, mouth MNs do not receive their visual input from parietal regions. Such information related to face/communicative behaviors could come from the ventrolateral prefrontal cortex. Further strong connections derive from limbic structures involved in encoding emotional facial expressions and motivational/reward processing. These brain structures include the anterior cingulate cortex, the anterior and mid-dorsal insula, orbitofrontal cortex and the basolateral amygdala. The mirror mechanism is therefore composed and supported by at least two different anatomical pathways: one is concerned with sensorimotor transformation in relation to reaching and hand grasping within the traditional parietal-premotor circuits; the second one is linked to the mouth/face motor control and is connected with limbic structures, involved in communication/emotions and reward processing.


Dr. Bibbo's Presidential Address on Automation in Cytology: Were Her Predictions Right, Wrong, or Somewhere in the Middle?
In 1983, Dr. Marluce Bibbo gave the Presidential Address at the Annual Meeting of the American Society of Cytology in Denver, CO, USA. The lecture was entitled "Analytic and Quantitative Cytology," a field in which Dr. Bibbo was intimately involved. In the presentation, she included a summary of 30 years of work already accomplished, the present state of the art, and musings about issues encountered, potential resolutions, progress that needed to be made, and her perception of how the field needed to evolve in order to become ultimately successful as a clinical service. This commentary looks back 34 years, with observations about Dr. Bibbo's predictions and how the field of cytology automation did actually evolve in the decades following her address. New challenges are identified and possible paths forward are discussed.


Evaluating the Profitability of Foliar Fungicide Programs in Mid-Atlantic Soft-Red Winter Wheat Production.
In mid-Atlantic soft-red winter wheat (SRWW) production, the standard timing for a fungicide application is between flag leaf emergence (Feekes growth stage [FGS] 8) and heading (FGS 10.5). However, two-pass and anthesis (FGS 10.5.1) applications are becoming common, although these programs have not been thoroughly evaluated for disease control, yield, and profitability. Experiments were conducted in the mid-Atlantic in 2015 and 2016 to evaluate fungicide programs with applications at FGS 8, FGS 10.5.1, and two-pass programs with an early application at green-up (FGS 5) followed by (FB) applications at either FGS 8 or FGS 10.5.1. Fungicide programs that included an application at FGS 10.5.1 resulted in the highest probability of no disease on the flag leaf (0.29 to 0.40). The estimated mean yield increases ( D¯ ) relative to the nontreated check ranged from 253.65 to 634.16 kg ha-1. Using a grain price of $0.18 kg-1 ($5 bushel-1), probabilities were similar between applications at FGS 8 (0.49 to 0.56) and FGS 10.5.1 (0.53). The probability of profitability ranged from 0.48 to 0.57 for FGS 5 FB FGS 8 applications and 0.52 to 0.59 for FGS 5 FB FGS 10.5.1 applications, indicating limited benefit to two-pass programs.


Alkane hydroxylase from Acinetobacter sp. strain ADP1 is encoded by alkM and belongs to a new family of bacterial integral-membrane hydrocarbon hydroxylases.
Degradation of long-chain alkanes by Acinetobacter sp. strain ADP1 involves rubredoxin and rubredoxin reductase. We complemented a mutant deficient in alkane utilization and sequenced four open reading frames (ORFs) on the complementing DNA. Each of these ORFs was disrupted by insertional mutagenesis on the chromosome. As determined from sequence comparisons, ORF1 and ORF4 seem to encode a rotamase of the PpiC type and an acyl coenzyme A dehydrogenase, respectively. Disruption of these ORFs does not affect alkane utilization. In contrast, the two other ORFs, alkR and alkM, are essential for growth on alkanes as sole carbon sources. alkR encodes a polypeptide with extensive homology to AraC-XyIS-like transcriptional regulators. It is located next to alkM, which encodes the terminal alkane hydroxylase, but is in the opposite orientation. Sequence homologies with other bacterial integral-membrane hydrocarbon hydroxylases suggest that AlkM may be the first member of a new protein family. The genes identified here are not linked to the rubredoxin- and rubredoxin reductase-encoding genes on the Acinetobacter sp. strain ADP1 chromosome.


Effect and mechanism of modification treatment on ammonium and phosphate removal by ferric-modified zeolite.
In this study, the reason for the decline of ammonium sorption capacity by zeolite after ferric modification and the effect of modification treatment on ammonium and phosphate removal by ferric-modified zeolite were studied. Modification treatment media (Na salt and HCl) and Na concentration (0.1 and 0.9 mol/L) have been investigated. Zeolites have been characterized by SEM, XRD, BET and XRF; meanwhile, CEC and pHpzc have been also determined. Equilibrium batch sorption for ammonium and phosphate individually and kinetics batch sorption for ammonium were conducted. The results showed a decline in sorption capacity or diffusion coefficients for ammonium but an increase for phosphate after ferric modification. The decrease of surface negative charge was the main contributor for the former, but iron loading did not well account for the latter. The performance of 0.1 mol/L Na modification treatment was better than other treatments for ammonium sorption and equal to HCl modification treatment for phosphate sorption, and the enhancement extent increased for ammonium but declined for phosphate when Na concentration increased. The advantage of Na modification treatment for ammonium was due to the enhancement of textural properties and high exchange rate with ammonium.


IL-6/BSF-2 selectively stimulates the GO----S progression of CD8+ lymphocytes.
IL-6 preferentially promotes the DNA synthesis of human peripheral blood CD8+, rather than CD4+, lymphocytes in presence of PHA: this effect is observed in serum-free cultures of greater than 99% purified CD8+ lymphocytes. However, IL-6 is able to stimulate DNA synthesis of CD8+ lymphocytes triggered by a mitogenic anti-CD2 mAb, but not by anti-CD3 mAb: these results suggest that IL-6 selectively induces activation of CD8+ lymphocytes through the CD2 rather than the CD3 pathway. Limiting dilution analysis indicates that accessory cells are not required to mediate the action of IL-6 on CD8+ cells. Furthermore, this action is not blocked by addition of mAb neutralizing either IL-2 or IL2R, thus suggesting that IL-6 does not act via IL-2. CD8+ lymphocytes grown in the presence of PHA + IL-6 incorporate (3H)-thymidine to the same extent as those stimulated with PHA + IL-2, but do not increase in number until day 6 of culture. It is hence apparent that the stimulating activity of IL-6 on CD8+ lymphocytes is restricted to the GO----S phase progression, but does not lead to mitosis. IL-6 receptors are expressed on resting CD4+ and CD8+ lymphocytes: their expression is significantly enhanced on both activated CD4+ and CD8+ cells. Scatchard analysis of (125I)-IL-6 binding data showed the presence of high (Kd, 3 x 10(-10) M) and low (Kd, 6 x 10(-8) M) affinity IL6R on both lymphocyte populations. Similarly, mRNA encoding IL6R was detected in both CD4+ and CD8+ lymphocytes. Thus, our studies indicate that IL-6 directly and selectively stimulates the GO----S progression of CD8+ lymphocytes in the presence of mitogen and absence of IL-2: this phenomenon may be of interest for the elucidation of mechanisms activating cytotoxic T lymphocytes.


Rearrangements of Nitrile Imines: Ring Expansion of Benzonitrile Imines to Cycloheptatetraenes and Ring Closure to 3-Phenyl-3 H-diazirines.
Nitrile imines are important intermediates in 1,3-dipolar cycloaddition reactions, and they are also known to undergo efficient, unimolecular rearrangements to carbodiimides via 1 H-diazirines and imidoylnitrenes under both thermal and photochemical reaction conditions. We now report a competing rearrangement, revealed by CASPT2(14,12) and B3LYP calculations, in which C-phenylnitrile imines 8 undergo ring expansion to 1-diazenyl-1,2,4,6-cycloheptatetraenes 12 akin to the phenylcarbene-cycloheptatetraene rearrangement. Amino-, hydroxy-, and thiol-groups in the meta positions of C-phenylnitrile imine lower the activation energies for this rearrangement so that it becomes potentially competitive with the cyclization to 1 H-diazirines and hence rearrange to carbodiimides. The diazenylcycloheptatetraenes 12 thus formed can evolve further to cycloheptatetraene 30 and 2-diazenyl-phenylcarbene 16 over modest activation barriers, and the latter carbenes cyclize very easily to 2 H- and 3 H-indazoles, from which 6-methylenecyclohexadienylidene, phenylcarbene, fulvenallene, and their isomers are potentially obtainable. Moreover, another new rearrangement of benzonitrile imine forms 3-phenyl-3 H-diazirine, which is a precursor of phenyldiazomethane and hence phenylcarbene. This reaction is competitive with the ring expansion. The new rearrangements predicted here should be experimentally observable, for example, under matrix photolysis or flash vacuum pyrolysis conditions.


William Benjamin Carpenter and the Emerging Science of Heredity.
In the nineteenth century, farmers, doctors, and the wider public shared a family of questions and anxieties concerning heredity. Questions over whether injuries, mutilations, and bad habits could be transmitted to offspring had existed for centuries, but found renewed urgency in the popular and practical scientific press from the 1820s onwards. Sometimes referred to as "Lamarckism" or "the inheritance of acquired characteristics," the potential for transmitting both desirable and disastrous traits to offspring was one of the most pressing scientific questions of the nineteenth century. As I argue in this paper, Carpenter's religious commitments to abolition and the temperance movement shaped his understanding of heredity. But this also committed him to a body of evidence for the inheritance of acquired characteristics that was coming under criticism for being untrustworthy. Carpenter used his popular treatises on physiology to promote these older, familiar ideas about heredity because they provided vital means of arguing for the unity of mankind and the hereditary dangers of intemperance. While early nineteenth century physiology has been seen by some historians as a challenge to religious authority, given its potentially materialist accounts of the body and the actions of the soul, this paper demonstrates how the missionary and institutional activities of the Unitarian church were ideologically supported by Carpenter's publications.


[Expression and significance of metallothionein in the placenta of women with low level lead exposure during pregnancy].
To investigate the significance of metallothionein (MT) expression in the placenta of women exposed to low level lead during pregnancy. Sixty-seven pregnant women with blood lead level ranging from 1.5 micromol/L to 4.8 micromol/L were randomly selected from the Department of Obstetrics of Qingdao Municipal Hospital between Mar 2005 and Mar 2006. Among them, 35 were with blood lead level less than 2.9 micromol/L (group A) and 32 more than 2.9 micromol/L (group B). Immunohistochemical streptavidin-peroxidase-biotin methods were used to observe the expression of MT in the placental tissue. (1) Among the 67 pregnant women, the highest level of blood lead was 4.7 micromol/L, and the lowest level was 1.6 micromol/L. The blood lead level of groups A and B was (1.7 +/- 0.3) micromol/L, and (3.1 +/- 0.4) micromol/L, with a significant difference between them (P < 0.05). (2) The positive expression of MT was mainly cytoplastic in the cytotrophoblast, decidual cell and small vascular endothelial cells. The positive cell staining was diffuse or scattered. (3) The positive staining of MT was 91% (29/32) and 74% (26/35) in the placental tissue of groups A and B, respectively, with a significant difference between them (P < 0.05). (4) The blood lead level of pregnant women was correlated with the expression of MT of placenta. Lead can induce the expression of MT in the placental tissue in a dose-dependent manner. MT is mainly located in the cytotrophoblast, decidual cell and small vascular endothelial cells of the placenta. MT expression in the placenta is important to the structural integrity and function of the placenta.


Farm level survey of spore-forming bacteria on four dairy farms in the Waikato region of New Zealand.
The aim of our study was to determine the occurrence and diversity of economically important spore-forming bacteria in New Zealand dairy farm systems. Farm dairy effluent (FDE) collected from Waikato dairy farms were tested for the presence of spore-forming bacteria, using a new culture-based methodology followed by genomic analysis. An enrichment step in which samples were inoculated in cooked meat glucose starch broth under anaerobic conditions, aided in the differential isolation of Bacillus and Clostridium species. Furthermore, the use of molecular methods such as ERIC genotyping, 16S rRNA gene sequence analysis identified different spore-forming bacteria present in FDE. C. sporogenes signature PCR gave further information on the phylogenetic relationship of the different Clostridium spp. isolated in this study. In total 19 Bacillus spp., 5 Paenibacillus spp. and 17 Clostridium spp. were isolated from farm dairy effluent. Sequence types similar to economically important food spoilage bacteria viz: C. butyricum, C. sporogenes and members of the Paenibacillus Genus were isolated from all four farms, whereas, sequence types similar to potential toxigenic, B. cereus, C. perfringens, C. butyricum, and C. botulinum were found on at least three of the farms. Sampling of farm dairy effluent provides a good indicator of farm level prevalence of bacterial load as it is used to irrigate dairy pasture in New Zealand. This study highlights the presence of various spore-forming bacteria in dairy waste water and indicates the implementation of good hygienic farm practices and dairy waste effluent management.


IFI30 expression predicts patient prognosis in breast cancer and dictates breast cancer cells proliferation via regulating autophagy.
Introduction: Incidence and mortality rates of breast cancer are increasing in women worldwide. Immunotherapy is a relatively popular treatment modality for all malignant tumors including breast cancer in recent years. Interferon γ-inducible protein 30 (IFI30) could catalyze the reduction of disulfide bonds and enhance major histocompatibility complex (MHC) class II-restricted antigen processing. Recent studies showed that IFI30 played an important role in the immune response of malignant tumors. Methods: The Cancer Genome Atlas (TCGA) database and clinical proteomic tumor Analysis consortium (CPTAC) database were applied to predict the role of IFI30 in breast cancer and the relationship between IFI30 and prognosis of breast cancer patients. Then we detected the expression of IFI30 in clinical samples of breast cancer patients, and analyzed the relationship between IFI30 and the prognosis of breast cancer patients. We used lentivirus infection method to construct a stable IFI30 knockdown cell line, and detected the effect of IFI30 in breast cancer cells. Nude mice tumor bearing experiment was performed to investigate the effect of IFI30 on breast cancer cells in vivo. Western blot was used to verify the regulation of autophagy related protein LC3 and p62 by IFI30. Results: We found that IFI30 was highly expressed in breast cancer tissues and was associated with poor outcome of patients. The knockdown of IFI30 could inhibit the proliferation, migration and invasion of breast cancer cells and significantly inhibit tumor growth in vivo. Increased accumulation of LC3-II and p62 suggested impaired autophagy in IFI30 knockdown cells. Discussion: As a result, we suggested that IFI30 might play a key role in the initiation and progression of human breast cancer and might be a new therapeutic target in breast cancer.


Carbonic anhydrase IX: a new druggable target for the design of antitumor agents.
Carbonic anhydrases (CAs, EC 22.214.171.124) are a family of enzymes widespread in all life kingdoms. In mammals, isozyme CA IX is highly overexpressed in many cancer types being present in few normal tissues. Its expression is strongly induced by hypoxia present in many tumors, being regulated by the HIF transcription factor and correlated with a poor response to classical chemo- and radiotherapies. CA IX was recently shown to contribute to acidification of the tumor environment, by efficiently catalyzing the hydration of carbon dioxide to bicarbonate and protons with its extracellularly situated active site, leading both to the acquisition of metastasic phenotypes and to chemoresistance with weakly basic anticancer drugs. Inhibition of this enzymatic activity by specific and potent inhibitors was shown to revert these acidification processes, establishing a clear-cut role of CA IX in tumorigenesis. The development of a wide range of potent and selective CA IX inhibitors belonging to diverse chemical classes, such as membrane-impermeant, fluorescent or metal-containing such agents, could thus provide useful tools for highlighting the exact role of CA IX in hypoxic cancers, to control the pH (im)balance of tumor cells, and to develop novel diagnostic or therapeutic applications for the management of tumors. Indeed, both fluorescent inhibitors or positively charged, membrane impermeant sulfonamides have been recently developed as potent CA IX inhibitors and used as proof-of-concept tools for demonstrating that CA IX constitutes a novel and interesting target for the anticancer drug development.


Molecular puzzle ring: pseudo[1]rotaxane from a flexible cyclodextrin derivative.
A pseudo[1]rotaxane formed by a flexible cyclodextrin (CD) derivative (1-R) with a bulky end group has been investigated on kinetic quantitation. 1-Rs have the cinnamamide moiety as a guest and a bulky end group (R) as a rate-determining moiety of the threading process. The R groups play an important role for the formation of pseudo[1]rotaxane, and kinetics of the self-inclusion process was found to be controlled by the size and shapes of the R groups. 1-Ad and 1-Me derivatives, which have an adamantyl and methyl end group, respectively, formed self-inclusion complexes by threading of the arm moiety with a conformational conversion of altrose from (1)C(4) form to (4)C(1) form. Flexibility of the altro-alpha-CD cavity resulted in an induced fit (from (1)C(4) to (4)C(1)) to the arm moiety, and introducing a bulky end group allowed the stability of this pseudo[1]rotaxane to be enhanced.


Resection of a large multisegmental filum terminale ependymoma through a multisegmental hemilaminectomy.
This video demonstrates a gross-total resection of a multisegmental intradural extramedullary tumor using only multisegmental hemilaminectomy. The patient is a 21-year-old woman presenting with only backache. MRI of the lumbar spine demonstrates a large multisegmental heterogeneously enhancing intradural extramedullary tumor extending down from the eleventh dorsal vertebrae down to the fifth lumbar vertebrae. The surgical video demonstrates the technique of multisegmental hemilaminectomy and microsurgical resection of the tumor without posterior spinal instrumentation. Postoperatively, the patient had no neurological deficit and was discharged on postoperative day 5. Three-month postoperative MRI shows no residual disease or spinal deformity.


A model of secretory protein trafficking in recombinant AtT-20 cells.
After their synthesis, secretory proteins in animal cells undergo a series of transport and processing steps before they are secreted. The amount and quality of protein obtained in culture medium depends on the rates of these intracellular steps. We present a model of recombinant protein trafficking in mouse pituitary AtT-20 cells based on currently available biological knowledge, plausible hypotheses, and quantitative secretion results, and we use it to simulate the dynamics of basal and induced secretion and to predict the dynamics of intracellular trafficking events. Besides the endoplasmic reticulum and Golgi, the model recognizes a conversion compartment (CC) where final processing of protein occurs, a storage compartment from which protein is secreted only in the presence of secretion stimulus, and constitutive and pseudoregulated (PR) pathways of secretion. The model further assumes that the protein flux is split between CC and PR and that the storage compartment exerts a negative feedback on protein flux through CC. The model predictions are compared with experimental results on secretion of human growth hormone (hGH) and insulin related peptides and on accumulation of hGH upon removal of secretion stimulus. The model is in agreement with data when either of two hypotheses is implemented: (a) cells always exhibit a high sorting efficiency at the trans-Golgi, but CC has the capacity to process only a fraction of the protein flux leaving the Golgi compartment; (b) the processing capacity of CC never becomes saturated, but significant missorting at the trans-Golgi occurs; in the case, the protein flux toward the plasma membrane becomes split both at the trans-Golgi cisternae and between CC and PR. The usefulness of the type of model considered in providing a quantitative description of intracellular events and in designing new experiments is discussed.


Side-Chain Type Polysulfates: Their Synthesis, AIE Properties and Applications for p-Nitrophenol Detection in Water.
Two small molecular monomers, ph-TPE and ph-TPE-CN, and their homopolymers Poly (ph-TPE) and Poly (ph-TPE-CN) containing tetra phenylethylene and sulfate structures, were synthesized by a sulfur (VI) fluorine exchange click reaction (SuFEx) and radical polymerization. All the monomers and polymers exhibit a typical aggregation-induced emission (AIE) effect both in the solid state and aggregated state. Moreover, based on the intermolecular charge transfer (ICT) effect between the tetra phenylethylene chromophore and p-nitrophenol, both polymers could be used for the selective detection of p-nitrophenol. The detection limit and reactivity coefficient of Poly (ph-TPE) are 0.081 μM and 5.15×104 M-1 , respectively, whereas the detection limit and reactivity coefficient of Poly (ph-TPE-CN) are 0.077 μM and 1.81×104 M-1 , respectively. This can be attributed to the greater sensitivity of Poly (ph-TPE-CN) to p-nitrophenol than that of Poly (ph-TPE). This work provides a new methodology for the preparation and broadening application of side-chain type AIE-active polysulfate fluorescent probes.


Pathophysiology and medical management of systemic hypertension and pre-eclampsia in pregnancy.
Hypertension in pregnancy includes a group of distinct disorders that require special consideration in both prevention and pharmacological treatment. In recent years, there have been few advances regarding the pathophysiology and prevention of pre-eclampsia, however there have been some promising studies regarding possible modes of screening women for preeclampsia before clinical signs and symptoms are apparent. The recommendations for first-line drug therapy for the hypertensive complications of pre-eclampsia, and the recommendations for pharmacological treatment of women with chronic hypertension antedating pregnancy, have changed little primarily because first-line medications have the advantage of having had more extensive research experience. Recent clinical trials have demonstrated the efficacy and safety of various second-line drugs for the hypertensive disorders of pregnancy; whether these therapies can eventually replace the standard recommended medications will require more extensive long-term investigation.


[Assessment of the American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the knee].
Radiological examination is essential in diagnosing osteoarthritis (OA) of the knee. However, diagnoses that are not based on radiological examination are preferred in epidemiological studies, and the American College of Rheumatology (ACR) has recommended classification criteria for OA of the knee based on clinical examination, and indicated that these classification criteria were appropriate for epidemiological studies. To evaluate the validity of this criteria, we examined the interobserver reproducibility as well as the sensitivity and specificity of the criteria for outpatient attenders complaining knee pain with wide spectrum of rheumatic diseases. As a result, interobserver reproducibility was considered good, but both sensitivity and specificity were slightly lower than the report by ACR in which representative rheumatic diseases such as rheumatoid arthritis were chosen as control. We therefore consider that ACR classification criteria for OA of the knee in of value, but that radiological examination should be preferred in case it is possible.


Human myometrial adaptation to pregnancy: cDNA microarray gene expression profiling of myometrium from non-pregnant and pregnant women.
The human uterus undergoes profound physiological tissue remodelling during pregnancy. In the myometrium, altered gene expression must underlie these extensive molecular and structural changes. The purpose of this study was to compare expression profiles of pregnant and non-pregnant myometrium, in order to identify genes that participate in this process. mRNA from 14 non-pregnant and four pregnant human myometrial samples were analysed using a human UniGEM V microarray with 7075 cDNA elements. A total of 602 transcripts from the microarray were up-regulated >/=2.0-fold in pregnant myometrium, with 37 transcripts up-regulated >/=4.0-fold. In contrast, eight transcripts were down-regulated >/=2.0-fold in pregnancy. To ensure accurate representation of differential gene expression, Northern blot analyses using total RNA from 16 samples of non-pregnant and pregnant myometrium were used to examine mRNA levels for four of the genes that were differentially expressed by microarray analysis, namely plasminogen activator inhibitor type 1 (PAI-1), milk fat globule-EGF factor 8 protein (MFGE8), secreted frizzled-related protein 4 (sFRP4) and estrogen receptor alpha (ERalpha). On the microarray these transcripts were up-regulated 7.5-fold for PAI-1 and 4.9-fold for MFGE8 in pregnant myometrium, and down-regulated 3.7-fold for sFRP4 and 2.9-fold for ERalpha in pregnancy. Northern blot analyses confirmed these changes. Our findings suggest that microarray technology is a useful tool for examining global changes in gene expression that occur as the myometrium differentiates from non-pregnant to pregnant status. Defining these changes provides new insight into the structural and functional adaptations of human myometrium during pregnancy.


Is seroprevalence of HTLV-I/II among blood donors in India relevant?
Human T-cell lymphotropic virus type I/II (HTLV-I/II) is associated with certain hematologic and neurologic disorders. Seroprevalence studies demonstrate that the distribution of HTLV-I/II is heterogeneous worldwide and not specific to one region. Because blood is one of the major routes of transmission of the virus, blood banks of several countries routinely screen all blood donations for HTLV-I/II. The aim of the present study was to assess the seroprevalence rate of HTLV-I/II antibodies among Indian blood donors and to confirm the positive rates by polymerase chain reaction (PCR). Between Jan 2004 to May 2005, consecutive blood samples of 10,000 blood donors were collected at the blood bank of Armed Forces Medical College, Pune. The samples were screened for HTLV-I/II by enzyme-linked immunosorbent assay (ELISA) method. Screening resulted in 18 (0.18%) positive samples, of which 14 (77.8%) samples were also positive by PCR. The prevalence of HTLV-I/II carriers in India seems to be negligible and is not a major public health hazard. Hence, routine screening of Indian blood donors for antibody to HTLV-I/II is not warranted due to its low prevalence in India.


Water adsorption lifts the (2 × 1) reconstruction of calcite(104).
The adsorption of water on calcite(104) is investigated in ultra-high vacuum by density functional theory (DFT) and non-contact atomic force microscopy (NC-AFM) in the coverage regime of up to one monolayer (ML). DFT calculations reveal a clear preference for water to adsorb on the bulk-like carbonate group rows of the (2 × 1) reconstructed surface. Additionally, an apparent water attraction due to carbonate group reorientation suggest island formation for water adsorbed on the reconstructed carbonate group rows. Experimentally, water is found to exclusively occupy specific positions within the (2 × 1) unit cell up to 0.5 ML, to form islands at coverage between 0.5 and 1 ML, and to express a (1 × 1) structure at coverage of a full monolayer.


Importance Of Thorough Physical Examination: A Lost Art.
Several recent studies have described a deterioration in physical examination skills among modern physicians. Reasons hypothesized for this change are improvements in technology and time constraints. Poor physical exam skills are a noteworthy threat to patient safety as they can lead to incorrect as well as missed diagnoses, causing delays in timely implementation of life-saving treatments. Here, we present a case of extensive acute embolic strokes secondary to infective endocarditis. The patient was initially misdiagnosed as having Bell's palsy due to incorrect physical examination. Through this case, we highlight the importance of management guided by a thorough history and physical examination to minimize diagnostic errors.


[Clinical and statistical studies on male infertility and follow-up studies for pregnancy (II)].
Clinical and statistical studies were carried out on 369 infertile male patients who are increasing year by year visiting our clinic during the 3 years from January 1978 to December 1980. If divided into 5-year age groups, the highest frequency occurred in the 30 to 34 year-old age group. In the semen analysis, 23.8% of the patients showed azoospermia, and 48.5% oligozoospermia; the testicular volumes of these patients was generally small. Pathological examinations of their testis revealed germinal cell aplasia or hypospermatogenesis. In the hormonal examinations performed, serum LH and FSH levels in azoospermic and oligozoospermic patients showed a tendency to be higher than normal. Follow-up studies for pregnancy were performed on 242 cases. Among the 108 cases which we were able to study, 30 cases were able to give successful pregnancy, 17 of whom had been treated by clomiphene citrate, 2 by testosterone-clomiphene therapy, and 11 were untreated.


Assessment of English-French differential item functioning of the Satisfaction with Appearance Scale (SWAP) in systemic sclerosis.
The Satisfaction with Appearance Scale (SWAP) has been used to assess body image distress among people with the rare and disfiguring disease systemic sclerosis (SSc); however, it has not been validated across different languages groups. The objective was to examine differential item functioning of the SWAP among 856 Canadian English- or French-speaking SSc patients. Confirmatory factor analysis was used to evaluate the SWAP two-factor structure (Dissatisfaction with Appearance and Social Discomfort). The Multiple-Indicator Multiple-Cause model was utilized to assess differential item functioning. Results revealed that the established two-factor model of the SWAP demonstrated relatively good fit. Statistically significant, but small-magnitude differential item functioning was found for three SWAP items based on language; however, the cumulative effect on SWAP scores was negligible. Findings provided empirical evidence that SWAP scores from Canadian English- and French-speaking patients can be compared and pooled without concern that measurement differences may substantially influence results.


Bibliometric analysis of Oropouche research: impact on the surveillance of emerging arboviruses in Latin America.
Given the emergence and reemergence of viral diseases, particularly in Latin America, we would like to provide an analysis of the patterns of research and publication on Oropouche virus (OROV). We also discuss the implications of recent epidemics in certain areas of South America, and how more clinical and epidemiological information regarding OROV is urgently needed.


[Cardiovascular disorders in rheumatoid arthritis].
Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease. Traditional cardiovascular risk factors (including male sex, family history for cardiovascular disease, age, dyslipidaemia, arterial hypertension, diabetes mellitus, smoking and obesity) do not adequately account for the extent of cardiovascular disease in RA. The pathogenesis of accelerated atherosclerosis in RA is not clear. Increasing evidence suggests a key role of inflammation in the onset and progression of atherosclerosis. Endothelial dysfunction represents the earliest manifestation of atherosclerosis. Hypertension prevalence in patients with RA is higher than that in the general population, It is attributable risk to the development of future cardiovascular events. Despite its serious complications, control of hypertension is far from adequate in the general population and even more so in rheumatoid arthritis patients.


Pesticide handling and exposures among cotton farmers in the gambia.
There are substantial health hazards to farmers and the environment associated with pesticide use in developing countries. Based on observations by the authors and previous reports, most previous studies in Africa are descriptive in nature. The aim of this study was to investigate how cotton farmers are exposed to pesticides in The Gambia and quantify their pesticide exposures and provide information for the formulation of a policy on pesticide safety for the country. A representative sample of 20 cotton farmers in the Central and Upper River Divisions (CRD and URD) of The Gambia were surveyed by questionnaires. Dermal pesticide exposures among a subset of 10 farmer/pesticide applicators were assessed by dermal patch samples, observation, and postapplication questionnaires. The study revealed that a toxic organochlorine insecticide, Callisulfan (endosulfan), is frequently sprayed on cotton plants by the farmers. The farmers wore no protective equipment and were inadequately dressed for work with this pesticide. Laboratory analysis of the mixed formulation showed a wide range in the concentration of the pesticide solution among the farmer/pesticide applicators and dermal patch samples showed very high residues of endosulfan analytes on their body surfaces. A low level of awareness of pesticide toxicity prevails amonsg cotton farmers in The Gambia. There is a less than adequate control of pesticides and other hazardous agrichemicals in the country.


Phenotypic expression of I-A and I-E/C subregion determinants on murine thymocytes.
The expression of Ia antigens on murine thymocytes has been assessed by indirect immunofluorescence and flow microfluorometry analysis. Antisera specific for I-region determinants were found to react with at least 50% of thymus cells in single-cell suspensions. When these antisera were tested on thymus cells of an appropriate recombinant strain, it was found that both I-A and I-E/C subregion determinants could be detected. Monoclonal antibodies to I-A and to I-E determinants also reacted with thymus cells in a similar fashion, eliminating the possibility that contaminating specificities accounted for the reactivity of alloantisera. The majority of Ia-positive thymus cells appeared to express determinants encoded by genes of both I-A and I-E/C subregions. Ia expression on individual thymocytes was also correlated with cell size as measured by forward light scatter intensity. However, unlike antigens detected by rabbit anti-mouse brain antisera, Ia antigens did not appear to be associated with known subpopulations of thymocytes distinguishable by light scatter intensity. The presence of I-region encoded antigens on thymocytes may play a role in maturation of T cells in the thymus microenvironment.


Simultaneous determination of 5-hydroxyindoles and catechols by high-performance liquid chromatography with fluorescence detection following derivatization with benzylamine and 1,2-diphenylethylenediamine.
A highly selective and sensitive method for the simultaneous determination of 5-hydroxyindoles and catechols (serotonin, norepinephrine, dopamine and related compounds) by high-performance liquid chromatography with fluorescence detection is described. The method is based on the two-step precolumn derivatization of 5-hydroxyindoles and catechols with benzylamine (BA) and 1,2-diphenylethylenediamine (DPE), respectively, resulting in highly fluorescent and stable benzoxazole derivatives. The first derivatization with BA proceeds at room temperature (ca. 23 degrees C) for 2 min in a mixture of 0.3 M 3-cyclohexylamino-1-propanesulfonic acid buffer (pH 10.0) and methanol in the presence of potassium hexacyanoferrate(III). The subsequent second derivatization with DPE is carried out at 50 degrees C for 20 min in the presence of glycine. The resulting fluorescent derivatives of five 5-hydroxyindoles and seven catechols are separated on a reversed-phase column (150 x 1.5 mm I.D., packed with C18 silica, 5 microm) with isocratic elution using a mixture of acetonitrile-15 mM acetate buffer (pH 4.5) (34:66, v/v) containing 1 mM octanesulfonic acid sodium salt, and are detected spectrofluorimetrically at 480 nm with excitation at 345 nm. The detection limits (signal-to-noise ratio of 3) of the related compounds are 80 amol to 86 fmol for a 20-microl injection.


Production, purification and characterization of an aspartic protease from Aspergillus foetidus.
An acidic thermostable protease was extracellularly produced either in shake flask or in stirred tank bioreactor by an Aspergillus foetidus strain isolated from the Brazilian savanna soil using different nitrogen sources. Its maximum activity (63.7 U mL-1) was obtained in a medium containing 2% (w/v) peptone. A cultivation carried out in a 5.0 L stirred-tank bioreactor provided a maximum protease activity 9% lower than that observed in Erlenmeyer flasks, which was obtained after a significantly shorter (by 16-29%) time. Protease purification by a combination of gel-filtration chromatography resulted in a 16.9-fold increase in specific activity (248.1 U g-1). The estimated molecular weight of the purified enzyme was 50.6 kDa, and the optimal pH and temperature were 5.0 and 55 °C, respectively. The enzyme was completely inhibited by pepstatin A, and its activity enhanced by some metals. According to the inhibition profiles, it was confirmed that the purified acid protease belongs to the aspartic protease type. These results are quite promising for future development of large-scale production of such protease, which can be useful in biotechnological applications requiring high enzyme activity and stability under acidic conditions.


Aggregating exposures & cumulating risk for semivolatile organic compounds: A review.
Increasingly, health risk assessment is addressing multiple pathway exposures to multiple contaminants. We reviewed aggregated exposure and cumulative risk approaches for contemporary and ubiquitous semivolatile organic compounds (SVOC). We identified 22 studies aggregating exposure pathways, and 31 cumulating risk. Exposure aggregation is based on the addition of pathway-specific doses, using kinetic modeling where it exists, and classic external dose equations otherwise. In most cases, exposure is dominated by a single route or source of exposure - mainly the oral pathway - via dietary or non-dietary exposure. Preferential routes and sources of exposure are influenced by SVOC physical-chemical properties such as vapor pressure. The cumulative risk approach for contaminants is based on dose addition. Simple sum of hazard quotient (Hazard Index: HI) is the most commonly used cumulative risk assessment approach, while Relative Potency Factor (RPF) appeared to the best suited - although this calls for a level of toxicological information that limits the number of compounds that can be studied simultaneously. Where both were performed, moving from HI to more refined approach produced similar results. In conclusion, both approaches - exposure aggregation and cumulative risk - rely on simple assumptions. Nevertheless, they allow uncertainty to be reduced, in comparison with source-by-source or chemical-by-chemical approaches.


Human monocytes CD36 and CD16 are signaling molecules. Evidence from studies using antibody-induced chemiluminescence as a tool to probe signal transduction.
A panel of monoclonal antibodies (mAb) directed against human monocyte surface antigens was tested for their capacity to mediate signal transduction by measuring luminol-enhanced chemiluminescence (CL). The response patterns fell into three categories. The mAb Mo4, OKM3, OKM6 and antibodies specific for Fc receptor (FcR) type I and II did not mediate signal transduction directly or were weak triggers, but upon second-order cross-linking by goat anti-mouse immunoglobulin (Ig) F(ab')2 or rabbit anti-mouse Ig, a strong CL response was induced. The mAb recognizing different epitopes on CD11b (complement receptor type III alpha chain) were unique in their ability to induce a CL response either by direct stimulation or by second-order cross-linking. The mAb 3G8 recognizing FcR type III (FcRIII; CD16) on a monocyte subpopulation and CD36-specific monoclonals directly elicited a CL response. A response of similar magnitude was obtained with 3G8 F(ab')2 or with intact 3G8. Furthermore, elutriation-centrifugation-purified monocytes were stimulated by 3G8 to a similar extent as unseparated mononuclear cells, whereas lymphocytes did not respond. This suggests that a FcRIII-expressing monocyte subpopulation may mediate effector functions, including the generation of reactive oxygen species, via FcRIII triggering. Our finding that anti-CD36 F(ab')2 directly induces an oxidative burst is the first evidence that CD36 itself is a trigger molecule. CD36, which is thought to interact with erythrocytes infected with Plasmodium falciparum and with thrombospondin, may constitute a signal-transducing element and thus may have functions extending beyond mediation of adherence. The present CL system constitutes a simple assay for detecting mAb directed against monocyte surface signalling elements. Probing mAb for signal transduction requires suspended cells and antibodies in the fluid phase in order to avoid inadvertent FcR triggering, which may occur when cells are stimulated by surface-adherent whole antibodies.


Increased Secondary/Primary Bile Acid Ratio in Chronic Heart Failure.
Bile acids (BAs) are now recognized as signaling molecules and emerging evidence suggests that BAs affect cardiovascular function. The gut microbiota has recently been linked to the severity of heart failure (HF), and microbial metabolism has a major impact on BA homeostasis. We aimed to investigate the pattern of BAs, and particularly microbiota-transformed (secondary) BAs, in patients with chronic HF. This was a prospective, observational, single-center study including 142 patients with chronic HF and 20 age- and sex-matched healthy control subjects. We measured plasma levels of primary, secondary, and total BAs, and explored their associations with clinical characteristics and survival. Plasma levels of primary BAs were lower (P < .01) and the ratios of secondary to primary BAs higher (P < .001) in patients with HF compared with control subjects. Approximately 40% of patients in the upper tertile of the ratio of secondary to primary BAs died during 5.6 years of follow-up (unadjusted Cox regression: hazard ratio 1.93, 95% confidence interval 1.01-3.68, compared with the lower tertiles). However, this association was attenuated and no longer significant in multivariate analyses. Levels of primary BAs were reduced and specific secondary BAs increased in patients with chronic HF. This pattern was associated with reduced overall survival in univariate analysis, but not in multivariate analyses. Future studies should assess the regulation and potential role of BA metabolism in HF.


Full-mouth antimicrobial photodynamic therapy in Fusobacterium nucleatum-infected periodontitis patients.
The purpose of this study is to clinically and microbiologically evaluate the effect of photodynamic therapy (PDT) as a full-mouth procedure in Fusobacterium nucleatum-infected patients with periodontitis. In the present study, PDT is administered adjuvantly after scaling and root planing (SRP) to patients with localized chronic periodontitis (LCP). Twenty-four patients, in whom only F. nucleatum was detected by baseline polymerase chain reaction (PCR) after SRP, were randomly assigned to PDT and control groups. PDT was carried out once as a full-mouth disinfection in the test group. The control group was treated with the photosensitizer solution, but without laser irradiation. In all subjects, the clinical parameters plaque index, reddening, bleeding on probing (BOP), probing depth (PD), gingival recession, and clinical attachment level (CAL) were determined at the baseline examination and at 1, 4, and 12 weeks after PDT. Quantitative analysis of the F. nucleatum DNA concentration was performed by competitive PCR. All clinical indices were calculated for each test and control subject as were the median and interquartile range of each group. In patients with LCP who received PDT treatment, significant reductions in reddening, BOP, and mean PD and CAL were observed during the observation period and with respect to controls. Four and 12 weeks after PDT, the mean PD and CAL showed significant differences from baseline values and from those of the control group. In the PDT group, 12 weeks after treatment, the F. nucleatum DNA concentration was found to be significantly reduced compared to the baseline level. The results of this study show that the adjuvant application of the described PDT method is appropriate to reduce periodontal inflammatory symptoms and to successfully treat infection with F. nucleatum.


Arnold-Chiari malformation type 1 complicated by sudden onset anterior spinal artery thrombosis, tetraparesis and respiratory arrest.
Chiari in 1891 described a constellation of anomalies at the base of the brain inherited congenitally, the characteristic of which are (1) extension of a tongue of cerebellar tissue posterior to the medulla and cord that extends into the cervical spinal canal; (2) caudal displacement of the medulla and the inferior part of the fourth ventricle into the cervical canal; and (3) a frequent but not invariable association with syringomyelia or a spinal developmental abnormality. Chiari recognized four types of abnormalities. Presently, the term has come to be restricted to Chiari's types I and II, that is, to cerebellomedullary descent without and with a meningomyelocele, respectively. The association of Arnold-Chairi malformation and high cervical cord infarction is unusual. The most common syndrome, anterior spinal artery syndrome (ASAS), is caused by interruption of blood flow to the anterior spinal artery, producing ischaemia in the anterior two-thirds of the cord, with resulting neurologic deficits. Causes of ASAS include aortic disease, postsurgical, sepsis, hypotension and thromboembolic disorders. The authors present an interesting case of cervical cord infarction due to anterior spinal artery thrombosis in a patient of type 1 Arnold-Chiari malformation without any of the above predisposing factors.


Modification by temperature of the response of isolated aorta to stimulatory agents and transmural stimulation.
Contractile responses of helically-cut strips of the rabbit aorta to drugs, ions and transmural electrical stimulation were compared at different temperatures of the bathing medium, the response at 37 degrees C being taken as control. The dose-response curve of norepinephrine was moved to the right and downward by lowering the temperature from 37 to 25 degrees C and by raising temperature to 40 degrees C. Responses to transmural neural stimulation at frequencies of 5 and 20/sec were attenuated at 25 degrees C, the attenuation being greater in the response at the lower frequency. Concentrations of exogenous norepinephrine needed to produce the same magnitude of contraction as that with transmural stimulation were markedly increased by lowering the temperature to 25 degrees C. Contractile responses to norepinephrine (2 X 10(-6) M), histamine (2 X 10(-5) M) and angiotensin II (10(-7) M) were attenuated by 32-44% at 25 degrees C, whereas the responses to K+ (25 mM) and Ba++ (2 mM) were dependent on temperatures between 25 and 37 degrees C and were attenuated by 69 and 92%, respectively, at 25 degrees C. Contractures induced by Ca++ in K+-depolarized preparations exposed to Ca++-free media and also by Ba++ in preparations exposed to Ca++-free media varied directly by raising temperatures. Interference with the influx of divalent cations, such as Ca++ and Ba++, may be involved in the cold inhibition of aortic contractility.


Effect of differing temperature cycles on broiler performance.
Commercial male broilers were used in five trials conducted to determine whether lowering the temperature during the cool portion of the 24-hr period in summer affected broiler performance. Treatments used were 24-hr linear temperature cycles ranging from a high of 35 C to a low of either 26.7 or 21.1 C. Results obtained showed that lowering the low portion of the temperature cycle from 26.7 to 21.1 C during the 24-hr period significantly increased broiler body weight at 48 days of age.


[Correction of baldness using a grafting method].
Hair grafting techniques, which have now been performed for more than 25 years and which have undergone considerable progress as the result of refinement of technical details and development of new instruments, are frequently criticized because of the high incidence of poor results, in particular the thinned appearance of the grafted hair. The purpose of this paper is to show that the poor results are due to poor technique and that the principle of hair grafts is still perfectly valid. Observation of a number of technical and instrumental details: haemostasis by pneumatic compression during the operation, double-bevelled circular scalpel, variable speed electric motor, preliminary infiltration of the donor and recipient sites, oblique angle of incision with the scalpel, together with the advantage of minor, outpatient surgery, allows excellent aesthetic results to be obtained in the majority of cases.


In Silico Identification of Natural Product-Based Inhibitors Targeting IL-1β/IL-1R Protein-Protein Interface.
IL-1β mediates inflammation and regulates immune responses, cell proliferation, and differentiation. Dysregulation of IL-1β is linked to inflammatory and autoimmune diseases. Elevated IL-1β levels are found in patients with severe COVID-19, indicating its excessive production may worsen the disease. Also, dry eye disease patients show high IL-1β levels in tears and conjunctival epithelium. Therefore, IL-1β signaling is a potential therapeutic targeting for COVID-19 and aforementioned diseases. No small-molecule IL-1β inhibitor is clinically approved despite efforts. Developing such inhibitors is highly desirable. Herein, a docking-based strategy was used to screen the TCM (Traditional Chinese Medicine) database to identify possible IL-1β inhibitors with desirable pharmacological characteristics by targeting the IL-1β/IL-1R interface. Primarily, the docking-based screening was performed by selecting the crucial residues of IL-1β interface to retrieve the potential compounds. Afterwards, the compounds were shortlisted on the basis of binding scores and significant interactions with the crucial residues of IL-1β. Further, to gain insights into the dynamic behavior of the protein-ligand interactions, MD simulations were performed. The analysis suggests that four selected compounds were stabilized in an IL-1β pocket, possibly blocking the formation of an IL-1β/IL-1R complex. This indicates their potential to interfere with the immune response, making them potential therapeutic agents to investigate further.


Dopamine terminal loss and onset of motor symptoms in MPTP-treated monkeys: a positron emission tomography study with 11C-CFT.
We studied the time course of dopamine (DA) terminal loss in three macaca fascicularis injected with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intravenously every 10-14 days for up to 389 days. Striatal DA terminal loss was monitored in vivo by positron emission tomography using 11C-CFT (WIN 35,428), a cocaine derivative that labels the DA transporter. The 11C-CFT uptake rate constant in the striatum of MPTP-treated monkeys decreased exponentially over time, with the putamen significantly more affected than the caudate. Spontaneous locomotor activity decreased in parallel with the decline of the 11C-CFT uptake rate; however, overt parkinsonian signs appeared only after the 11C-CFT uptake rate had declined to about 30% of the pretreatment values. We conclude that a long-term intermittent mode of administration of MPTP can lead to a pattern of terminal loss that closely resembles idiopathic Parkinson disease.


RIP140 deficiency enhances cardiac fuel metabolism and protects mice from heart failure.
During the development of heart failure (HF), the capacity for cardiomyocyte (CM) fatty acid oxidation (FAO) and ATP production is progressively diminished, contributing to pathologic cardiac hypertrophy and contractile dysfunction. Receptor-interacting protein 140 (RIP140, encoded by Nrip1) has been shown to function as a transcriptional corepressor of oxidative metabolism. We found that mice with striated muscle deficiency of RIP140 (strNrip1-/-) exhibited increased expression of a broad array of genes involved in mitochondrial energy metabolism and contractile function in heart and skeletal muscle. strNrip1-/- mice were resistant to the development of pressure overload-induced cardiac hypertrophy, and CM-specific RIP140-deficient (csNrip1-/-) mice were protected against the development of HF caused by pressure overload combined with myocardial infarction. Genomic enhancers activated by RIP140 deficiency in CMs were enriched in binding motifs for transcriptional regulators of mitochondrial function (estrogen-related receptor) and cardiac contractile proteins (myocyte enhancer factor 2). Consistent with a role in the control of cardiac fatty acid oxidation, loss of RIP140 in heart resulted in augmented triacylglyceride turnover and fatty acid utilization. We conclude that RIP140 functions as a suppressor of a transcriptional regulatory network that controls cardiac fuel metabolism and contractile function, representing a potential therapeutic target for the treatment of HF.


Transvaginal mesh surgery for pelvic organ prolapse: one-year outcome analysis.
The aim of the study was to assess the role of Prolift + M (PP-PG) vaginal mesh surgery to correct uterovaginal prolapse not only from an anatomic but also a subjective (patient's) standpoint. A prospective cohort of subjects treated with transvaginal mesh for prolapse between April 2009 and November 2010 was analyzed. A composite score that included subjective criteria of absence of a bothersome bulge and objective criteria based on Pelvic Organ Prolapse Quantification lower than stage II was used to assess treatment success. Transvaginal mesh was performed in 157 subjects (age, 64.7 ± 11.6 years; body mass index, 28.5 ± 4.8 kg/m) for pelvic organ prolapse. Five anterior mesh surgeries (3.2%), 48 posterior mesh surgeries (30.6%), and 104 total mesh surgeries (66.2%) were performed in subjects with stage II or greater degrees of prolapse. Stage II prolapse was noted in 44 subjects (28.0%), 91 subjects (58.0%) had stage III prolapse, and 22 subjects (14.0%) had stage IV prolapse. The mean follow-up was 13 months. Our composite success score was 88.1%. Pure anatomic success based on Pelvic Organ Prolapse Quantification lower than stage II was 94%. The mean operative time was 117.8 ± 42.4 minutes. The mean intraoperative blood loss was 106.1 ± 116.4 mL. There were 3 cases (2.2%) of mesh exposure in the vagina. There were no visceral injuries. The incidence of de novo dyspareunia was 6%. Transvaginal PP-PG mesh surgery is safe and effective with few postoperative morbidities.


Innovative substance 2250 as a highly promising anti-neoplastic agent in malignant pancreatic carcinoma - in vitro and in vivo.
Former studies already revealed the anti-neoplastic properties of the anti-infective agent Taurolidine (TRD) against many tumor species in vitro and in vivo. Its anti-proliferative and cell death inducing capacity is largely due to its main derivative Taurultam (TRLT). In this study it could be demonstrated, that substance 2250 - a newly defined innovative structural analogue of TRLT - exhibits an anti-neoplastic effect on malignant pancreatic carcinoma in vitro and in vivo. The anti-neoplastic potential of substance 2250 as well as its mode of action was demonstrated in extensive in vitro analysis, followed by successful and effective in vivo testings, using xenograft models derived from established pancreatic cancer cell lines as well as patient derived tissue. Our functional analysis regarding the role of oxidative stress (ROS) and caspase activated apoptosis showed, that ROS driven programmed cell death (PCD) is the major mechanisms induced by substance 2250 in pancreatic carcinoma. What is strongly relevant towards clinical practice is especially the observed inhibition of patient derived pancreatic cancer tumor growth in mice treated with this new substance in combination with its sharply higher metabolic stability. These encouraging results provide new therapeutical opportunities in pancreatic cancer treatment and build the basis for further functional analysis as well as first clinical studies for this promising agent.


Hepatic and Skeletal Muscle Autophagy Marker Levels in Rat Models of Prenatal and Postnatal Protein Restriction.
Fetal growth restriction (FGR) leads to adult-onset metabolic syndrome. Intrauterine and early postnatal caloric restriction ameliorates the risk in animal models. To understand the underlying mechanism, we compared autophagic marker levels between offspring with FGR and those with prenatal and early postnatal protein restriction (IPPR). We postulated that FGR would impair, whereas IPPR would help regulate, autophagy in neonatal rats. This study involved control (Con), FGR offspring (Pre), and IPPR offspring groups (Pre + Post); n = 5/group. We assessed the abundance of autophagy markers in the liver and skeletal muscles. At birth, the Pre group pups had lower levels of some autophagy-related proteins, with increased p62 expression and a low microtubule-associated protein light chain beta (LC3-II:LC3-I) ratio. This finding suggests a lower hepatic autophagy flux in FGR offspring than the Con group. The hepatic levels of autophagy proteins were considerably decreased in the Pre and Pre + Post groups at 21 days of age compared to the Con group, but the LC3-II:LC3-I ratio was higher in the Pre + Post group than in the Con and Pre groups. The muscle levels of beclin-1, LC3-II, and p62 were lower in the Pre group pups, with no difference in the LC3-II:LC3-I ratio among the groups. An imbalance in the nutritional environment is associated with downstream autophagic flux, thus suggesting that FGR offspring will have impaired autophagic flux, and that post-natal nutrition restriction might help reduce this risk.


Diagnostic accuracy of diffusion-weighted whole-body imaging with background body signal suppression/T2-weighted image fusion for the detection of abdominal solid cancer.
Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) images show significant contrast for cancer tissues against non-cancerous tissues. Fusion of a DWIBS and a T2-weighted image (DWIBS/T2) can be used to obtain functional, as well as anatomic, information. In the present study, the performance of DWIBS/T2 in the diagnosis of abdominal solid cancer was evaluated. The records of 14 patients were retrospectively analyzed [5 patients with hepatocellular carcinoma (HCC), 4 with metastatic liver cancer, 3 with pancreatic cancer, 1 with renal cellular carcinoma and 1 with malignant lymphoma of the para-aortic lymph node]. T1WI and T2WI scans did not detect pancreatic cancer in certain cases, whereas DWIs and DWIBS/T2 clearly demonstrated pancreatic cancer in all cases. In addition, metastatic liver cancer and HCC were successfully detected with abdominal US and CECT; however, US did not detect pancreatic cancer in 1 case, while CECT and DWIBS/T2 detected pancreatic cancer in all cases. In conclusion, the diagnostic performance of DWIBS/T2 was the same as that of abdominal US and CECT in detecting primary and metastatic liver cancer. DWIBS/T2 enabled the diagnosis of pancreatic cancer in cases where it was not detected with US, T1WI or T2WI.


Prospective association of dopamine-related polymorphisms with smoking cessation in general care.
Genetic contributions to nicotine dependence have been demonstrated repeatedly, but the relevance of individual polymorphisms for smoking cessation remains controversial. We examined genotypes at two dopamine-related loci, DRD2/ANKK1 (rs1800497) and DBH (rs77905), in 577 heavy smokers participating in a prospective study of smoking cessation in general care in Germany. Smoking status after 1 year was significantly associated with DRD2/ANKK1, odds of abstinence being 4.4-fold (95% CI: 1.5-12.9) increased in TT- versus CC-homozygous subjects (p = 0.008). No effect was observed for the DBH genotype. The smoking cessation drug bupropion appeared to be particularly effective in CC-homozygotes (among CC subjects there was a 28% higher cessation probability among those taking buproprion; among T carrier subjects there was an increase only by 12%). The large effects observed for DRD2/ANKK1 might be related to our study design, in which individual therapy was decided by the physician. Further studies are needed to clarify the genetic effects of DRD2/ANKK1 especially in 'real-life' settings outside clinical trials.


Novel short antimicrobial peptide isolated from Xenopus laevis skin.
A rich source of bioactive peptides, including a large number of antimicrobial peptides, has been found in amphibian skin. In this study, a novel short antimicrobial peptide was purified from Xenopus laevis skin and characterised through reversed-phase high-performance liquid chromatography, Edman degradation and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. The peptide was composed of six amino acids with a sequence of DEDLDE and thus named X. laevis antibacterial peptide-P2 (XLAsp-P2). Transmission electron microscopy revealed that this peptide showed potential antimicrobial abilities against bacteria by damaging the bacterial cell membrane. XLAsp-P2 maybe inhibit bacterial growth by binding to the microbial genomic DNA. The peptide also exhibited a weak haemolytic activity against rabbit red blood cells. Therefore, XLAsp-P2 is a novel short anionic antibacterial peptide with broad activities. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.


Th2 cytokines are associated with persistent hepatic fibrosis in human Schistosoma japonicum infection.
We conducted a prospective cohort study in Leyte, the Philippines, among 611 Schistosoma japonicum-infected participants 7-30 years old, all of whom were treated with praziquantel at baseline. To detect hepatic fibrosis, abdominal ultrasound was performed at baseline and 12 months after treatment. Stool for assessment of S. japonicum infection was collected at baseline and at 3, 6, 9, and 12 months after treatment. Cytokines (interleukin [IL]-4, IL-5, IL-10, IL-13, tumor necrosis factor- alpha , and interferon- gamma ) produced by peripheral-blood mononuclear cells in response to soluble worm antigen preparation (SWAP), soluble egg antigen (SEA), and control medium were measured once 4 weeks after treatment. IL-4 to SWAP and IL-10 to both SWAP and SEA were associated with the presence of baseline fibrosis after adjustment for potential confounding variables (P<.03, for all). In participants with fibrosis at baseline, IL-4 to SWAP and IL-5 and IL-13 to both SWAP and SEA were associated with persistent fibrosis at 12 months after treatment (P<.05, for all). Males showed consistently stronger T helper 2 (Th2) cytokine responses to both SWAP and SEA than did females (P<.02, for all). These results suggest an independent role for Th2-biased cytokine responses to S. japonicum antigens in persistent hepatic fibrosis and indicate that Th2 cytokines may contribute to the male-biased prevalence of fibrosis.


Effects of lesions to the left lateral prefrontal cortex on task-specific top-down biases and response strategies in blocked-cyclic naming.
Anders, Riès, van Maanen and Alario put forward evidence accumulation modelling of object naming times as an alternative to neural network models of lexical retrieval. The authors exemplify their approach using data from the blocked-cyclic naming paradigm, requiring speakers to repeatedly name small sets of related or unrelated objects. The effects observed with this paradigm are understood reasonably well within the tradition of neural network modelling. However, implemented neural network models do not specify interfaces for task-specific top-down influences and response strategies that are likely to play a role in the blocked-cyclic naming paradigm, distinguishing it from continuous, non-cyclic manipulations of the naming context. I argue that the evidence accumulation approach falls short on this account as well, as it does not specify the potential contribution of task-specific top-down processes and strategic facilitation effects to the response time distributions. Future endeavours to model or fit data from blocked-cyclic naming experiments should strive to do so by simultaneously considering data from continuous context manipulations.


Effects of hyperventilation with face mask on brain network in patients with epilepsy.
During the ongoing pandemic of COVID-19, wearing face masks was recommended, including patients with epilepsy doing the hyperventilation (HV) test during electroencephalogram (EEG) examination somewhere. However, evidence was still limited about the effect of HV with face mask on cortical excitability of patients with epilepsy. The motivation of this work is to make use of the graph theory of EEG to characterize the cortical excitability of patients with epilepsy when they did HV under the condition wearing a surgical face mask. We recruited 19 patients with epilepsy and 17 normal controls. All of participants completed two HV experiments, including HV with face mask (HV+) and HV without a mask (HV). The interval was 30 min and the sequence was random. Each experiment consisted of three segments: resting EEG, EEG of HV, and EEG of post-HV. EEG were recorded successively during each experiment. Participants were asked to evaluate the discomfort degree using a questionnaire when every HV is completed. All of the participants felt more uncomfortable after HV + . Moreover, not only HV decreased small-worldness index in patients with epilepsy, but also HV + significantly increased the clustering coefficient in patients with epilepsy. Importantly, the three-way of Mask*HV*Epilepsy showed interaction in the clustering coefficient in the delta band, as well as in the path length and the small-worldness index in the theta band. The results of this study indicated that patients with epilepsy showed the increased excitability of brain network during HV + . We should pay more attention to the adverse effect on brain network excitability caused by HV + in patients with epilepsy. In the clinical practice under the COVID-19 pandemic, it is important that the wearing face mask remain cautious for the individuals with epilepsy when they carried out HV behavior such as exercise (e.g., running, etc.).


Hormone-inactive pituitary macroadenoma: an uncommon cause for the syndrome of inappropriate antidiuresis.
A 76-year-old patient was admitted with dizzy spells and fainting. Laboratory analysis indicated the syndrome of inappropriate antidiuresis, which was further characterized as type C ("reset osmostat"). Extended workup revealed a hormone - inactive pituitary macroadenoma. After complete transsphenoidal resection, serum sodium levels and plasma and urinary osmolality promptly normalized. Except for the gonadal axis, the anterior pituitary functions remained intact. There was no adenoma recurrence over a five-year follow-up, and repetitive testing on ad libitum fluid intake showed normal sodium concentrations. Thus, the pituitary macroadenoma represents the sole detectable cause for the syndrome of inappropriate antidiuresis in this patient.


Mode of invasion and lymph node metastasis in squamous cell carcinoma of the oral cavity.
The relationship between the mode of tumor invasion in the tumor-host borderline and the frequency of regional lymph node metastasis was investigated in squamous cell carcinoma of the oral cavity. Cases with grades 1-3 mode of invasion classified by modified Jacobsson criteria showed a low frequency of metastasis (10/72, 13.9%), while those cases with grade 4 mode of invasion, which consisted of grade 4C (cord-like type) and grade 4D (diffuse type) showed a high frequency of metastasis (4C:11/18,61.1%; 4D :9/12,75.0%; total 20/30,66.7%). Moreover, the number of metastatic nodes in each case of mode of invasion ranged from 1 to 3 in grades 1-3, from 1 to 5 in grade 4C, and from 1 to 7 in grade 4D . The presence of metastasis indicated a poorer prognosis than did the absence of the mode of invasion in each grade, especially in grades 4C and 4D .


Efficacy and safety of sublingual fentanyl orally disintegrating tablets in patients with breakthrough pain: multicentre prospective study.
The aim of this study was to evaluate the effectiveness and safety of sublingual fentanyl oral disintegrating tablets (sublingual fentanyl ODT) for the treatment of breakthrough pain (BTP), cancer or non-cancer related, in terms of relief of pain intensity, adverse events (AEs) and patient satisfaction, and to further examine the clinical and epidemiological profile of patients with BTP in a clinical setting. A multicentre, prospective, open-label study was conducted in 19 pain units from Catalonia hospitals (Spain) over a 1-month period. Opioid-tolerant adult patients experiencing episodes of BTP intensity >5 on a visual analogue scale (VAS) during the 12-24 h before screening or AEs related to their previous rescue medication for BTP received sublingual fentanyl ODT in the course of routine clinical practice and completed a 30-day study period consisting of five assessment points: days 0 (baseline), 3, 7, 15 and 30. The efficacy was assessed by collecting pain intensity and pain relief data at baseline and at each assessment. AEs were recorded by investigators throughout the study during clinic visits and telephone follow-ups. For all patients, titration was begun with an initial dose of 100 μg. No more than two doses were allowed to treat an episode and patients might wait at least 4 h before treating another BTP episode with sublingual fentanyl ODT. The dose was increased by 100 μg multiples up to 400 μg as needed; and by 200 μg multiples up from 400 to 800 μg, the maximum titration step. A total of 182 patients were enrolled and 177 (97.2 %) completed the study: 37 had breakthrough cancer pain (BTcP) and 145 had breakthrough non-cancer pain (BTncP). The mean pain intensity showed a statistically significant improvement at the first assessment point and at all assessments thereafter (p < 0.0001). At the end of the study, the time lag between administration and first effect of sublingual fentanyl ODT was ≤10 min in 69.0 % (60 % BTcP and 71.2 % BTncP). The number of daily BTP episodes decreased in both groups, but it was statistically significant in BTcP. 114 patients (62.64 %) experienced AEs during the study. AEs recorded included nausea, vomiting, somnolence and constipation, and seven (4.49 %) were considered severe. No death or discontinuation was considered related to AEs. Sublingual fentanyl ODT provided rapid and consistent relief from BTP, both in cancer and non-cancer patients. It was well-tolerated and well-accepted by patients in routine clinical practice.


Temperature and relative humidity influence the ripening descriptors of Camembert-type cheeses throughout ripening.
Ripening descriptors are the main factors that determine consumers' preferences of soft cheeses. Six descriptors were defined to represent the sensory changes in Camembert cheeses: Penicillium camemberti appearance, cheese odor and rind color, creamy underrind thickness and consistency, and core hardness. To evaluate the effects of the main process parameters on these descriptors, Camembert cheeses were ripened under different temperatures (8, 12, and 16°C) and relative humidity (RH; 88, 92, and 98%). The sensory descriptors were highly dependent on the temperature and RH used throughout ripening in a ripening chamber. All sensory descriptor changes could be explained by microorganism growth, pH, carbon substrate metabolism, and cheese moisture, as well as by microbial enzymatic activities. On d 40, at 8°C and 88% RH, all sensory descriptors scored the worst: the cheese was too dry, its odor and its color were similar to those of the unripe cheese, the underrind was driest, and the core was hardest. At 16°C and 98% RH, the odor was strongly ammonia and the color was dark brown, and the creamy underrind represented the entire thickness of the cheese but was completely runny, descriptors indicative of an over ripened cheese. Statistical analysis showed that the best ripening conditions to achieve an optimum balance between cheese sensory qualities and marketability were 13±1°C and 94±1% RH.


Neuron-specific enolase serum levels predict severe neuronal injury after extracorporeal life support in resuscitation.
Extracorporeal life support (ECLS) is a rescue option in critically ill patients. Since fast available and appropriate for respiratory and circulatory failure, it is frequently applied in resuscitation scenarios. Neurological injury is a complication common in ECLS patients limiting outcome, particularly after resuscitation. In this study, the institutional ECLS database was used to correlate neuron-specific enolase (NSE) serum peak values with outcome of patients supported with venoarterial (VA) ECLS during cardiopulmonary resuscitation (CPR). From January 2011 to August 2012, 31 patients were provided with a VA ECLS during CPR (external cardiac massage). Serum NSE peaks were monitored and correlated with neurological outcome and hospital mortality. Patients were divided into two groups with mild-to-moderate and high NSE levels (cut-off value 100 μg/l). High NSE levels were seen in 7 patients (mean 218 ± 155 μg/l) and mild-to-moderate levels in 24 patients (50 ± 23 μg/l, P = 0.0001). Duration of extracoporeal support was comparable in both groups (6.3 ± 7.5 vs 5.0 ± 4.5 days, P = n.s.). Patients with mild-to-moderate NSE levels were significantly older than those with high NSE levels (58 ± 16 vs 44 ± 15 years, P = 0.02). Six patients with high NSE levels (86%) developed severe neurological complications. Though 4 patients could be weaned from extracorporeal support, hospital mortality was 86% (6 patients). In contrast, patients with mild-to-moderate NSE levels had a hospital mortality of 46% (11 patients). Eighteen patients (75%) could be weaned from the device, and incidence of major neurological events was 29% (6 patients) only. Serum pH and lactate levels before ECLS implantation were significantly lower in patients with mild-to-moderate NSE values (pH: 7.23 ± 0.04 vs 6.93 ± 0.12, P = 0.039; lactate: 106 ± 11 vs 161 ± 16 mg/l, P = 0.023). High NSE serum levels after ECLS correspond to poor neurological outcome and considerable mortality. Therefore, early neuroimaging is reasonable for determining therapeutic strategies in patients with high NSE peaks after resuscitation and extracorporeal support.


Voltage-gated calcium channels.
Voltage-gated calcium (Ca(2+)) channels are key transducers of membrane potential changes into intracellular Ca(2+) transients that initiate many physiological events. There are ten members of the voltage-gated Ca(2+) channel family in mammals, and they serve distinct roles in cellular signal transduction. The Ca(V)1 subfamily initiates contraction, secretion, regulation of gene expression, integration of synaptic input in neurons, and synaptic transmission at ribbon synapses in specialized sensory cells. The Ca(V)2 subfamily is primarily responsible for initiation of synaptic transmission at fast synapses. The Ca(V)3 subfamily is important for repetitive firing of action potentials in rhythmically firing cells such as cardiac myocytes and thalamic neurons. This article presents the molecular relationships and physiological functions of these Ca(2+) channel proteins and provides information on their molecular, genetic, physiological, and pharmacological properties.


Positive and negative ion fast atom bombardment mass spectrometry of glycosphingolipids. Discrimination of the positional isomers of gangliosides with sialic acids.
High molecular weight gangliosides (GD1a, GD1b, GT1a, and GT1b) and neutral glycosphingolipids (Forssman antigen, globoside, and CTH) containing various fatty acids were analyzed by positive and negative ion fast atom bombardment mass spectrometry (POS-FAB-MS and NEG-FAB-MS) without any derivatization. NEG-FAB-MS of the molecules gave intense peaks of the molecular ion species, (M-H)-, and many fragment ions useful for the elucidation of carbohydrate structure were also detected with significant intensity. The fragment ions were assessed to be cleaved at the glycosidic linkages sequentially from the non-reducing end with or without the ceramide portion and it was possible to distinguish structural isomers having different binding positions of sialic acid. All molecular ion species of neutral glycosphingolipids with various fatty acids were detected at intensities that were in accordance with the relative abundance of the fatty acids.


Reliability of immunoglobulin G antitoxoplasma avidity test and effects of treatment on avidity indexes of infants and pregnant women.
The immunoglobulin G antitoxoplasma avidity test (Vidas; BioMérieux) is an immunoenzymatic test useful for excluding acute infection after the onset of pregnancy. The avidity index (AI) is the ratio of the signal in a test sample washed with urea, which disrupts low-avidity complexes, to that washed without urea. An AI of >0.3 is taken to mean that infection had occurred more than 4 months ago. The increase of the AI with time and the influence of the different treatments given to pregnant women and their newborns were evaluated. A total of 59 pregnant women (271 sera) and their 60 neonates (199 sera) were tested from 1998 to 2002. There were five groups of women based on the type and duration of treatment given. Thirteen pregnant women (group 1) did not receive any treatment, 15 (group 2), 11 (group 3), and 17 (group 4) women received treatment with spiramycin (9 MIU/day) for 0.5 to 2, 2.5 to 5, and 5.5 to 8 months, respectively, and the last 3 women (group 5) received tritherapy (pyrimethamine-sulfonamide and spiramycin alternatively) for 1.5 to 2.5 months. All of the maternal sera collected in the first 6 months had an AI of <0.30, with a mean of 0.07 (range, 0.01 to 0.21). The increase was slow (0.02/month), and there was no significant difference when comparisons were made between the treatment groups. Neonates with proven maternofetal transmission had an increasing AI, unlike those without transmission. However, long-term therapy with pyrimethamine-sulfonamide, as opposed to treatment with spiramycin alone, was found to slow down the progression of the AI. An AI of >0.2 is sufficient to exclude acute infection in pregnant women. In neonates, it is not of major use to diagnose congenital infection; however, it could be a good indicator of compliance and efficacy of treatment of infected infants.


Ten steps to a successful disease management program.
This primer article suggests the 10 basic steps a health plan must take to successfully create and implement an internal disease management program. Covering everything from patient identification to staffing to educational materials, the author focuses on congestive heart disease and diabetes examples.


Cobalt-Catalyzed Asymmetric Alkylation of (Hetero)Arenes with Styrenes.
An efficient and general intermolecular Cobalt(II)-catalyzed asymmetric alkylation of styrenes with (hetero)arenes including indoles, thiophene and electron rich arenes has been developed, providing straightforward access to enantioenriched alkyl(hetero)arenes with high enantioselectivity. Mechanistic studies suggest that the reaction underwent a CoH-mediated hydrogen atom transfer (HAT) with alkenes, followed by a pivotal catalyst-controlled SN 2-like pathway between in situ generated organocobalt(IV) species and aromatic nucleophiles. This is the first CoH-catalyzed asymmetric hydrofunctionalization using carbon nucleophiles, providing a new strategy for asymmetric Friedel-Crafts type alkylation.


Design, Synthesis, and Functionalization of Imidazoheterocycles.
Over the years, various strategies have been reported for the synthesis of imidazo[1,2-a]pyridines due to their importance in different fields. In this account, we represent the methods developed by our group for the synthesis and functionalization of imidazo[1,2-a]pyridines. Different synthetic strategies have been developed using easily accessible reactants for this purpose. We envisage that these newly developed protocols will be very useful for the synthesis of functionalized molecules bearing imidazo[1,2-a]pyridine scaffolds. These strategies will also be attractive for the construction of other pharmaceutically important heterocycles.


Twelve tips for teaching medical students with dyslexia.
Dyslexia is a common learning difficulty. As a result of SS' own experiences as a medical student with dyslexia, we have been researching and teaching on this topic for the past two years. Here, we present twelve tips for teaching medical students with dyslexia. These are gathered from our personal experiences and research, discussions with other educators, and wider literature on the topic. This article aims to shed some light on dyslexia, and also to make practical suggestions. Teaching students with dyslexia should not be a daunting experience. Small changes to existing methods, at minor effort, can make a difference - for example, adding pastel colors to slide backgrounds or avoiding Serif fonts. These tips can help educators gain more insight into dyslexia and incorporate small, beneficial adaptations into their teaching.


Sleep-Disordered Breathing and Prognosis after Ischemic Stroke: It Is Not Apnea-Hypopnea Index That Matters.
Sleep-disordered breathing (SDB) is highly prevalent after stroke and is considered to be a risk factor for poor post-stroke outcomes. The aim of this observational study was to evaluate the effect of nocturnal respiratory-related indices based on nocturnal respiratory polygraphy on clinical outcomes (including mortality and non-fatal events) in patients with ischemic stroke. A total of 328 consecutive patients (181 (55%) males, mean age 65.8 ± 11.2 years old) with confirmed ischemic stroke admitted to a stroke unit within 24 h after stroke onset were included in the analysis. All patients underwent standard diagnostic and treatment procedures, and sleep polygraphy was performed within the clinical routine in the first 72 h after admission. The long-term outcomes were assessed by cumulative endpoint (death of any cause, new non-fatal myocardial infarction, new non-fatal stroke/transient ischemic attack, emergency revascularization, emergency hospitalization due to the worsening of cardiovascular disease). A Cox-regression analysis was applied to evaluate the effects of nocturnal respiratory indices on survival. The mean follow-up period comprised 12 months (maximal-48 months). Patients with unfavourable outcomes demonstrated a higher obstructive apnea-hypopnea index, a higher hypoxemia burden assessed as a percent of the time with SpO2 < 90%, a higher average desaturation drop, and a higher respiratory rate at night. Survival time was significantly lower (30.6 (26.5; 34.7) versus 37.9 (34.2; 41.6) months (Log Rank 6.857, p = 0.009)) in patients with higher hypoxemia burden (SpO2 < 90% during ≥2.1% versus <2.1% of total analyzed time). However, survival time did not differ depending on the SDB presence assessed by AHI thresholds (either ≥5 or ≥15/h). The multivariable Cox proportional hazards regression (backward stepwise analysis) model demonstrated that the parameters of hypoxemia burden were significantly associated with survival time, independent of age, stroke severity, stroke-related medical interventions, comorbidities, and laboratory tests. Our study demonstrates that the indices of hypoxemia burden have additional independent predictive value for long-term outcomes (mortality and non-fatal cardiovascular events) after ischemic stroke.