Effects of Persimmon Fruit Polyphenols on Postprandial Plasma Glucose Elevation in Rats and Humans.
Persimmon is a fruit rich in polyphenols (proanthocyanidins or condensed tannins). Using rats and humans, the effects of Kaki-tannin (Nara-type), persimmon polyphenols prepared using a new method, on postprandial plasma glucose levels were investigated in this study. Kaki-tannin (Nara-type) comprised mainly proanthocyanidins, composed of epicatechin : epicatechin gallate : epigallocatechin : epigallocatechin gallate in a ratio of 1 : 1 : 2 : 2 with a molecular weight of approximately 8,000 Da, with epicatechin gallate as a terminal unit. These polyphenols inhibited amylolytic enzymes, such as α-amylase, maltase, sucrase, and α-glucosidase in vitro, and sodium-dependent glucose transporter 1 in Caco-2 cells. These results suggested that the polyphenols suppressed digestion and absorption in the intestinal tract. The ingestion of 250 mg/kg body weight of the polyphenols significantly suppressed increased blood glucose levels after carbohydrate (2 g/kg body weight of glucose or maltose) loading in rats. In a human trial, 1.88 g of Kaki-tannin (Nara-type) significantly delayed increased plasma glucose levels after carbohydrate (150 kcal of maltooligosaccharides) loading. Thus, Kaki-tannin (Nara-type) holds promise to be developed as a food material that potentially improve blood glucose elevation after meals.


Paclitaxel decreases the accumulation of gemcitabine and its metabolites in human leukemia cells and primary cell cultures.
We identified a drug-drug interaction between gemcitabine and paclitaxel in a clinical pharmacokinetic study. The purpose of the present study was to determine whether paclitaxel affected the uptake and accumulation of the parent drug gemcitabine and the formation of its metabolites after treatment of cells with gemcitabine in vitro. The human leukemia cell line CEM was treated with 15 micoM 3H-gemcitabine, with and without paclitaxel, and the accumulation of radiolabeled gemcitabine was assessed up to one minute and one hour. Peripheral blood mononuclear cells (PMN) and hepatocytes were treated with gemcitabine, with or without paclitaxel, for specified amounts of time at three concentrations of gemcitabine, and the concentrations of gemcitabine and its metabolites were measured by liquid chromatography. In CEM cells, paclitaxel reduced the uptake and accumulation of gemctabine by 32% and 30%, respectively. In the hepatocytes, the mean concentrations of gemcitabine increased in the cell culture media 100%, 48% and 38% when treated with paclitaxel plus gemcitabine 5, 15 and 30 microM, respectively, compared to gemcitabine alone. The concentrations of the deaminated metabolite dFdU were significantly decreased in the cell culture media. In the PMN, the intracellular accumulation of active triphosphorylated metabolite dFdCTP was lower in cells treated with paclitaxel (up to 83%) compared to the control. Paclitaxel substantially reduced the uptake and accumulation of gemcitabine and the formation of its metabolites in vitro at clinically relevant concentrations.


SV40 mediates stable gene transfer in vivo.
Gene transfer in vivo requires an efficient, nonreplicating, transfer agent. We report here the efficacy of recombinant, replication-deficient SV40 in transferring firefly luciferase (luc) production to murine hematopoietic cells and selected internal organs in vivo. Replication-deficient SV40 was made by replacing the large T antigen gene (Tag) with a polylinker, into which luc cDNA (luc) was cloned. Luc expression was controlled by SV40 early promoter. Tag-, luc+ SV40 DNA was transfected into Tag-expressing cells to yield a replication-deficient SV40-derivative virus containing luc (SVluc). The ability of SVluc to transfer luc production in vivo was tested in two ways: SVluc was inoculated into BALB/C mice intravenously; also bone marrow cells treated with SVluc were infused into syngeneic hosts. Luc production was followed for 105 days by immunochemical analysis of peripheral blood and selected internal organs using anti-luciferase antibody, and by assay of luc enzyme activity in peripheral blood. Luc was found in 20-25% of peripheral blood nucleated cells from day 20 until > or = 105 days. Luc-producing cells were also identified in liver, spleen, brain, kidney, skin and colon from day 20, also until > or = 105 days. Analysis of whole blood showed fluctuating levels of functionally active luc enzyme beginning on day 21, and remaining substantially and significantly greater than control values to day 105. Thus, SV40 may transfer sustained expression of foreign genes to bone marrow and other organs, for at least 3 months.


Erythrocyte mean cellular volume and its relation to serum homocysteine, vitamin B12 and folate.
Cobalamin (B12) and folate deficiency is related to both increased erythrocyte mean cellular volume (MCV) and raised serum total homocysteine (tHcy) values. Furthermore, there are indications that B12 and folate serum values do not represent the tissue status of the two vitamins exactly. Therefore, a direct relationship between MCV and tHcy, if demonstrated, could support the hypothesis that tHcy is a better indicator for the cited vitamin status than the serum levels of B12 and folate. We studied MCV, gamma glutamyl transferase (GGT), serum B12, folate and tHcy values in 200 hospitalized patients. There was a significant correlation of MCV with GGT (r = 0.266, P < 0.001) and with tHcy (r = 0.248, P < 0.001), but not with serum B12 and folate. Stepwise multiple linear regression with MCV as dependent and GGT, B12, folate and tHcy as independent variables, respectively, revealed significant associations of MCV with GGT (B = 2.18, 95% CI 0.95-3.42, P = 0.001) and tHcy (B = 3.33, 95% CI 1.26-5.39, P = 0.002). By removing tHcy from this model, serum B12 became a significant predictor of MCV (B = -1.70, 95% CI -3.25 to -0.15, P = 0.032). Serum folate was not significantly associated with MCV in multivariate analysis. In conclusion, the present study confirms indications that serum B12 and folate values lack clinical sensitivity and specificity in diagnosing vitamin deficiency states by showing MCV was better associated to tHcy, than to B12 or folate serum levels. This observation demonstrates that tHcy may be useful in diagnosing patients with B12 and/or folate deficiency.


Iodine and cancer.
Thyroid carcinomas are the most frequent endocrine malignancies. Among thyroid carcinomas the most frequent types are the differentiated forms (follicular, papillary or mixed papillary-follicular), whereas anaplastic thyroid carcinoma and medullary thyroid carcinomas are rare. Animal experiments have demonstrated a clear increase in incidence of thyroid epithelial cell carcinomas after prolonged iodine deficiency leading to a situation of the thyroid gland by thyrotropin and possibly other growth factors. However, the overall incidence of differentiated thyroid carcinoma is generally not considered to be influenced by the iodine intake of a population, whereas the distribution of the types of thyroid carcinoma seems to be related to the intake of iodine, with fewer of the more aggressive follicular and anaplastic carcinomas and more papillary carcinomas in iodine rich areas. Populations starting iodine prophylaxis demonstrate an increase in the ratio of papillary to follicular carcinoma. Because a population with higher iodine intake usually has fewer benign nodules in the thyroid gland and the incidence of thyroid carcinomas is similar to an iodine-deficient region, the diagnostic work-up of nodules in the thyroid gland may become affected. The incidence of other cancers, such as breast cancer, may be influenced by the iodine intake, but too few studies are available at present. The present article summarizes available data from both epidemiological studies, animal experiments, and basic gene transfection studies. The overall incidence for a relationship between iodine and cancer is poor and future studies are warranted.


Extending the fossil record for foliicolous Dothideomycetes: Bleximothyrium ostiolatum gen. et sp. nov., a unique fly-speck fungus from the Lower Cretaceous of Virginia, USA.
Fossils can reveal long-vanished characters that inform inferences about the timing and patterns of diversification of living fungi. Through analyzing well-preserved fossil scutella, shield-like covers of fungal sporocarps, we describe a new taxon of early Dothideomycetes with a combination of characters unknown among extant taxa. Macerated clays from the Potomac Group, lower Zone 1, from the Lower Cretaceous (Aptian, 125-113 Ma) of Virginia USA yielded one gymnospermous leaf cuticle colonized by 21 sporocarps of a single fungal morphotype. We inferred a tree from nuclear ribosomal DNA of extant species, and coded morphological characters to evaluate alternative, equally parsimonious placements of the fossil in a molecular constraint tree of extant species. Bleximothyrium ostiolatum gen. et sp. nov. has an ostiolate scutellum of radiate, dichotomizing hyphae. Unlike otherwise similar extant and fossil taxa, B. ostiolatum has tangled hyphae at its scutellum margin. Scutella of B. ostiolatum are connected to superficial mycelium, to intercalary and lateral appressoria, and to extensive subcuticular "mycélium en palmettes". The gymnospermous host has characters consistent with identity as a non-papillate ginkgophyte or cycad. Bleximothyrium ostiolatum is the oldest known fossil fly-speck fungus that occurs on plant cuticles and has the radiate, ostiolate scutellum known only from Dothideomycetes. Its combination of characters, its scutellum margin, and mycélium en palmettes are unknown in other extant and fossil species, and Bleximothyrium ostiolatum likely represents a new group of fly-speck fungi that may now be extinct.


The DNA Damage Response in Fully Grown Mammalian Oocytes.
DNA damage in cells can occur physiologically or may be induced by exogenous factors. Genotoxic damage may cause cancer, ageing, serious developmental diseases and anomalies. If the damage occurs in the germline, it can potentially lead to infertility or chromosomal and genetic aberrations in the developing embryo. Mammalian oocytes, the female germ cells, are produced before birth, remaining arrested at the prophase stage of meiosis over a long period of time. During this extensive state of arrest the oocyte may be exposed to different DNA-damaging insults for months, years or even decades. Therefore, it is of great importance to understand how these cells respond to DNA damage. In this review, we summarize the most recent developments in the understanding of the DNA damage response mechanisms that function in fully grown mammalian oocytes.


Enhanced transpiration in response to wind effects at the edge of a blue gum (Eucalyptus globulus) plantation.
In Australia, tree planting has been widely promoted to alleviate dryland salinity and one proposed planting configuration is that of strategically placed interception belts. We conducted an experiment to determine the effect of tree position in a belt on transpiration rate. We also assessed how much the effect of tree position can be explained by advection and environmental conditions. Daily transpiration rates were determined by the heat pulse velocity technique for four edge and 12 inner trees in a 7-year-old Tasmanian blue gum (Eucalyptus globulus) plantation in South Australia. Various climatic variables were logged automatically at one edge of the plantation. The relationship between daily sap flow and sapwood area was strongly linear for the edge trees (r2 = 0.97), but only moderately correlated for the inner trees (r2 = 0.46), suggesting an edge effect. For all trees, sap flow normalized to sapwood area (Qs) increased with potential evaporation (PE) initially and then became independent as PE increased further. There was a fairly close correlation between transpiration of the edge and inner trees, implying that water availability was partially responsible for the difference between inner and edge trees. However, the ratio of edge tree to inner tree transpiration differed from unity, indicating differences in canopy conductance, which were estimated by an inverse form of the Penman-Monteith equation. When canopy conductances were less than a critical value, there was a strong linear relationship between Qs of the edge and inner trees. When canopy conductances of the edge trees were greater than the critical value, the slope of the linear relationship was steeper, indicating greater transpiration of the edge trees compared with the inner trees. This was interpreted as evidence for enhancement of transpiration of the edge trees by advection of wind energy.


Alterations in the rat serum proteome during liver injury from acetaminophen exposure.
Changes in the serum proteome were identified during early, fulminant, and recovery phases of liver injury from acetaminophen in the rat. Male F344 rats received a single, noninjury dose or a high, injury-producing dose of acetaminophen for evaluation at 6 to 120 h. Two-dimensional gel electrophoresis of immunodepleted serum separated approximately 800 stained proteins per sample from which differentially expressed proteins were identified by mass spectrometry. Serum alanine aminotransferase/aspartate aminotransferase levels and histopathology revealed the greatest liver damage at 24 and 48 h after high-dose acetaminophen corresponding to the time of greatest serum protein alterations. After 24 h, 68 serum proteins were significantly altered of which 23 proteins were increased by >5-fold and 20 proteins were newly present compared with controls. Only minimal changes in serum proteins were noted at the low dose without any histopathology. Of the 54 total protein isoforms identified by mass spectrometry, gene ontology processes for 38 unique serum proteins revealed involvement of acute phase response, coagulation, protein degradation, intermediary metabolism, and various carrier proteins. Elevated serum tumor necrosis factor-alpha from 24 to 48 h suggested a mild inflammatory response accompanied by increased antioxidant capability demonstrated by increased serum catalase activity. Antibody array and enzyme-linked immunosorbent assay analyses also showed elevation in the chemokine monocyte chemoattractant protein-1 and the metalloprotease inhibitor tissue inhibitor of metalloproteinases-1 during this same period of liver injury. This study demonstrates that serum proteome alterations probably reflect both liver damage and a concerted, complex response of the body for organ repair and recovery during acute hepatic injury.


Cardiorespiratory control: an integrated view. H.-P. Koepchen in memoriam.
H.-P. Koepchen's presence at this symposium on cardiocirculatory function during sleep would have given us an inspiring impetus. His death has meant a severe loss for all of us. Koepchen's integrated view on cardiorespiratory control and rhythmicity has been the content of his late work. His considerations as documented in various papers are used for this contribution. They are based on earlier experimental studies of spontaneous coordinations of rhythmic activities in anaesthetized dogs, conscious men, and microelectrode recordings and local cooling experiments in the brain stem of anaesthetized dogs and cats, which he had worked on together with his students.


Novel psychoactive substances: An investigation of temporal trends in social media and electronic health records.
Public health monitoring is commonly undertaken in social media but has never been combined with data analysis from electronic health records. This study aimed to investigate the relationship between the emergence of novel psychoactive substances (NPS) in social media and their appearance in a large mental health database. Insufficient numbers of mentions of other NPS in case records meant that the study focused on mephedrone. Data were extracted on the number of mephedrone (i) references in the clinical record at the South London and Maudsley NHS Trust, London, UK, (ii) mentions in Twitter, (iii) related searches in Google and (iv) visits in Wikipedia. The characteristics of current mephedrone users in the clinical record were also established. Increased activity related to mephedrone searches in Google and visits in Wikipedia preceded a peak in mephedrone-related references in the clinical record followed by a spike in the other 3 data sources in early 2010, when mephedrone was assigned a 'class B' status. Features of current mephedrone users widely matched those from community studies. Combined analysis of information from social media and data from mental health records may assist public health and clinical surveillance for certain substance-related events of interest. There exists potential for early warning systems for health-care practitioners.


Significance of p-STAT3 expression in human colorectal adenocarcinoma.
To examine the relationship between p-STAT3 and the clinicopathological parameters of colorectal adenocarcinoma (CRA), we initially conducted immunohistochemical (IHC) analyses on formalin-fixed tissues. A total of 127 invasive CRA, 20 colorectal adenomas and 20 normal mucosae were obtained. To clarify the validity of p-STAT3 as determined by the IHC analysis, quantitative real-time PCR was performed on fresh samples from 51 CRA-4 carcinomas in situ, 47 invasive CRA and on 51 normal mucosae. IHC analyses were conducted after formalin fixation from 51 CRA for comparison. The statistically significant difference of immunoreactivity for p-STAT3 between the CRA and adenoma, and between the CRA and normal mucosae was identified. Among the 174 CRA, p-STAT3 immunoreactivity significantly correlated with the T- and clinical stage. Among the 47 invasive CRA, the expression of STAT3 as determined by real-time PCR significantly correlated with tumor size, M stage and clinical stage. The overall findings of the real-time PCR analyses correlated with the findings of the IHC analyses. These findings suggest that p-STAT3 expression has an important role related to the tumorigenesis and tumor progression of CRAs. Moreover, IHC analysis is a reliable and useful modality of assessing the status of p-STAT3 expression in formalin-fixed samples.


A one-time pneumatic jet-injection of 5-fluorouracil and triamcinolone acetonide for treatment of hypertrophic scars-A blinded randomized controlled trial.
Patients with hypertrophic scars (HTS) risk reduced quality of life due to itching, pain, poor cosmesis, and restriction of movement. Despite good clinical efficacy, patients are often reluctant to undergo repeated needle injections due to pain or needle phobia. To evaluate the applicability of needle-free pneumatic jet injection (PJI) and assess changes in hypertrophic scars following a single PJI treatment with 5-fluorouracil (5-FU) and triamcinolone acetonide (TAC). Twenty patients completed this blinded, randomized, controlled, split-scar trial. The intervention side of the HTS received a one-time treatment with PJIs containing a mixture of TAC + 5-FU injected at 5 mm intervals (mean 7 PJI per HTS); the control side received no treatment. Assessments were made at baseline and 4 weeks posttreatment. Outcome measures included change in (1) Vancouver Scar Scale (VSS) total score and subscores, (2) scar volume and surface area assessed by three-dimensional imaging, (3) skin microarchitecture measured by optical-coherence tomography (OCT), (4) photo-assessed scar cosmesis (0-100), (5) patient-reported pain and satisfaction (0-10), and (6) depiction of drug biodistribution after PJI. PJI with TAC + 5-FU significantly decreased both HTS height (-1 VSS; p = 0.01) and pliability (-1 VSS; p < 0.01) with a nonstatistically significant reduction of -1 in total VSS score (0 in control; p = 0.09). On 3D imaging, a 33% decrease in scar volume (p = 0.016) and a 37% decrease in surface area (p = 0.008) was observed. OCT indicated trends towards smoother scar surface (Ra 11.1-10.3; p = 0.61), normalized dermal microarchitecture (attenuation coefficient: 1.52-1.68; p = 0.44), and a reduction in blood flow between 9% and 17% (p = 0.50-0.79). Despite advances in VSS subscores and OCT, no improved photo-assessed cosmesis was found (-3.2 treatment vs. -1.4 control; p = 0.265). Patient-reported pain was low (2/10) and 90% of the patients that had previously received needle injections preferred PJI to needle injection. Depositions of TAC + FU were imaged reaching deep into the scar at levels corresponding to the reticular dermis. A single PJI injection containing 5-FU and TAC can significantly improve the height and pliability of HTS. PJI is favored by the patients and may serve as a complement to conventional needle injections, especially for patients with needle phobia.


Sex differences in the behavioural and hypothalamic-pituitary-adrenal response to contextual fear conditioning in rats.
In recent years, special attention is being paid to sex differences in susceptibility to disease. In this regard, there is evidence that male rats present higher levels of both cued and contextual fear conditioning than females. However, little is known about the concomitant hypothalamic-pituitary-adrenal (HPA) axis response to those situations which are critical in emotional memories. Here, we studied the behavioural and HPA responses of male and female Wistar rats to context fear conditioning using electric footshock as the aversive stimulus. Fear-conditioned rats showed a much greater ACTH and corticosterone response than those merely exposed to the fear conditioning chamber without receiving shocks. Moreover, males presented higher levels of freezing whereas HPA axis response was greater in females. Accordingly, during the fear extinction tests, female rats consistently showed less freezing and higher extinction rate, but greater HPA activation than males. Exposure to an open-field resulted in lower activity/exploration in fear-conditioned males, but not in females, suggesting greater conditioned cognitive generalization in males than females. It can be concluded that important sex differences in fear conditioning are observed in both freezing and HPA activation, but the two sets of variables are affected in the opposite direction: enhanced behavioural impact in males, but enhanced HPA responsiveness in females. Thus, the role of sex differences on fear-related stimuli may depend on the variables chosen to evaluate it, the greater responsiveness of the HPA axis in females perhaps being an important factor to be further explored.


Teaching intonation to young deaf children with the intonation meter.
Incorrect production of intonation contours is a common phonatory problem in prelingually, profoundly deaf speakers. To help deaf speakers improve this, a visual display system for teaching intonation has been developed. In this system, called the Intonation Meter, visual feedback of intonation is given as a continuous representation of the pitch contour containing only the perceptually relevant aspects of the intonation pattern. This pitch-contour representation is supposed to facilitate the interpretation of the visual feedback of the pitch contour. A study was carried out, using a Single-Subject Design, in which subjects alternately received intonation training by means of regular methods and intonation training by means of regular methods in which also use was made of the Intonation Meter, to evaluate the effectiveness of the Intonation Meter for teaching intonation to young deaf children. Prelingually profoundly deaf children aged 6 to 7 years and 9 to 11 years participated in this study. The results showed that the 9 to 11 year old children showed most progress when the Intonation meter was used in intonation training whereas 6 to 7 year olds progressed well irrespective of whether or not the Intonation Meter was used, which is in accordance with the theory of a critical period for language learning. Alternatively, it is hypothesized that the cognitive requirements of the visual feedback might be to advanced for very young children to be helpful in learning to produce certain pitch contours.


A new strategy towards the synthesis of a room-temperature discotic nematic liquid crystal employing triphenylene and pentaalkynylbenzene units.
A new approach is reported for the design of a room-temperature discotic nematic (ND) liquid crystal (LC) dimer consisting of a triphenylene and a pentaalkynylbenzene unit linked via flexible alkyl spacers. The formation of the ND phase is realized most likely through folding of the dimeric molecule that prevent stacking between the triphenylene units, as suggested by modelling in the mesophase derived from X-ray scattering results and high-level DFT calculations.


The transformation of housing and household structures in France and Great Britain.
"In France and Great Britain, the last 30 years have seen considerable evolution in the housing stock...and in household structure....This article describes the dynamic interaction of processes influencing the evolution of both households and dwellings. In the two countries, the life course of individuals has become more and more complex. This translates into an ever greater variety of housing needs, not only at different stages in family life, but also in relation to growing job insecurity regardless of family situation. At the same time, policies encouraging home-ownership seem to have reached their limits, because of the new demand for rented accommodation. The answer to sociological and economic evolution cannot be found in a ¿single' type of housing and tenure status, but rather in a wide range of dwellings and in the development of a more flexible housing market."


The management of venous leg ulceration post the EVRA (early venous reflux ablation) ulcer trial: Management of venous ulceration post EVRA.
This survey study evaluates current management strategies for venous ulceration and the impacts of the EVRA trial results. An online survey was disseminated to approximately 15000 clinicians, through 12 vascular societies in 2018. Survey themes included: referral times, treatment times and strategies, knowledge of the EVRA trial and service barriers to managing venous ulceration. Data analysis was performed using Microsoft Excel and SPSS. 664 responses were received from 78 countries. Respondents were predominantly European (55%) and North American (23%) vascular surgeons (74%). Responses varied between different countries. The median vascular clinic referral time was 6 weeks and time to be seen in clinic was 2 weeks. This was significantly higher in the UK (p ≤ 0.02). 77% of respondents performed surgical/endovenous interventions prior to ulcer healing, the median time to intervention was 4 weeks. 31% of participants changed their practice following EVRA. Frequently encountered barriers to implementing change were a lack of operating space/time (18%). Venous ulcers are not managed as quickly as they should be. An evaluation of local resource requirements should be performed to improve service provision for venous ulceration. When interpreting the results of this survey consideration should be given to the response rate.


Spectroelectrochemical elucidation of B vitamins present in multivitamin complexes by EC-SERS.
Raman spectroelectrochemistry based on electrochemical surface-enhanced Raman scattering (EC-SERS) effect is an interesting alternative to overcome the lack of sensitivity of normal Raman spectroscopy. Electrochemical activation of metallic screen-printed electrodes (SPEs) leads to the reproducible generation of nanostructures with excellent SERS properties. In that way, gold SPEs circumvent the traditional reproducibility limitation and produce the enhancement of the Raman intensity to favor the detection of low concentrations. Furthermore, fingerprint features of Raman spectroscopy make possible the dynamic spectroelectrochemical analysis of B vitamins. The accuracy assignments of Raman bands associated with B1, B2, B3, B6 and B12 vitamins present in multivitamin complexes provides valuable information, allowing us not only the detection of B vitamin present in mixtures, but also to understand the interaction between vitamins and metallic SERS surfaces.


Pervanadate induces Mammalian Ste20 Kinase 3 (MST3) tyrosine phosphorylation but not activation.
The yeast Ste20 (sterile) protein kinase, which is a serine/threonine kinase, responds to the stimulation of the G proteincoupled receptor (GPCR) pheromone receptor. Ste20 protein kinase serves as the critical component that links signaling from the GPCR/G proteins to the mitogen-activated protein kinase (MAPK) cascade in yeast. The yeast Ste20p functions as a MAP kinase kinase kinase kinase (MAP4K) in the pheromone response. Ste20-like kinases are structurally conserved from yeast to mammals. The mechanism by which MAP4K links GPCR to the MAPK pathway is less clearly defined in vertebrates. In addition to MAP4K, the tyrosine kinase cascade bridges G proteins and the MAPK pathway in vertebrate cells. Mammalian Ste20 Kinase 3 (MST3) has been categorized into the Ste20 family and has been reported to function in the regulation of cell polarity and migration. However, whether MST3 tyrosine phosphorylation regulates diverse signaling pathways is unknown. In this study, the tyrosine phosphatase inhibitor pervanadate was found to induce MST3 tyrosine phosphorylation in intact cells, and the activity of tyrosine-phosphorylated MST3 was measured. This tyrosine-directed phosphorylation was independent of MST3 activity. Parameters including protein conformation, Triton concentration and ionic concentration influenced the sensitivity of MST3 activity. Taken together, our data suggests that the serine/threonine kinase MST3 undergoes tyrosinedirected phosphorylation. The tyrosine-phosphorylated MST3 may create a docking site for the structurally conserved SH2/SH3 (Src Homology 2 and 3) domains within the Src oncoprotein. The unusual tyrosinephosphorylated MST3 may recruit MST3 to various signaling components.


Establishment of axon-dendrite polarity in developing neurons.
Neurons are among the most highly polarized cell types in the body, and the polarization of axon and dendrites underlies the ability of neurons to integrate and transmit information in the brain. Significant progress has been made in the identification of the cellular and molecular mechanisms underlying the establishment of neuronal polarity using primarily in vitro approaches such as dissociated culture of rodent hippocampal and cortical neurons. This model has led to the predominant view suggesting that neuronal polarization is specified largely by stochastic, asymmetric activation of intracellular signaling pathways. Recent evidence shows that extracellular cues can play an instructive role during neuronal polarization in vitro and in vivo. In this review, we synthesize the recent data supporting an integrative model whereby extracellular cues orchestrate the intracellular signaling underlying the initial break of neuronal symmetry leading to axon-dendrite polarization.


Data reliability evaluation of flexible optical disk system using accelerated test of dust density.
The data reliability of a 90-mm flexible optical disk system with a phase-change rewritable disk is studied through accelerated tests of dust density for fabrication of low-cost, reliable flexible optical disks. A simple dust generator composed of a small loud speaker creates an extremely dusty environment in a chamber, with a dust density several times higher than in a normal environment. These accelerated tests indicate that a flexible optical disk contained in a semisealed cartridge will show no change in the number of errors over several years in a normal environment.


Functional insight into LOAD-associated microglial response genes.
Alzheimer's disease (AD) is characterized by the presence of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs), neuronal and synaptic loss and inflammation of the central nervous system (CNS). The majority of AD research has been dedicated to the understanding of two major AD hallmarks (i.e. Aβ and NFTs); however, recent genome-wide association studies (GWAS) data indicate neuroinflammation as having a critical role in late-onset AD (LOAD) development, thus unveiling a novel avenue for AD therapeutics. Recent evidence has provided much support to the innate immune system's involvement with AD progression; however, much remains to be uncovered regarding the role of glial cells, specifically microglia, in AD. Moreover, numerous variants in immune and/or microglia-related genes have been identified in whole-genome sequencing and GWAS analyses, including such genes as TREM2, CD33, APOE, API1, MS4A, ABCA7, BIN1, CLU, CR1, INPP5D, PICALM and PLCG2. In this review, we aim to provide an insight into the function of the major LOAD-associated microglia response genes.


[Radiotherapy of bone metastases].
Sixty percent of cancer patients have or develop bone metastases during the development of their cancer. Bone metastases are the most common cause of cancer-related pain. External radiation therapy is the standard treatment of uncomplicated bone metastases, for the treatment of pain, the prevention of fracture, and for tumor control. Fractionation schedules (one session of 8 Gy or several sessions, typically 30 Gy in 10 fractions) vary in terms of efficacy with however more retreatments after a single session. The treatment of spinal cord compression is classically based on radiotherapy associated or not with surgery with indications assessed in emergency by a multidisciplinary team. The use of prognostic scores and prospective studies including patients corresponding to the daily practice and the work of groups like the GEMO aim to harmonize and optimize the management of bone metastases.


Tranilast prevents activation of transforming growth factor-beta system, leukocyte accumulation, and neointimal growth in porcine coronary arteries after stenting.
N(3,4-dimethoxycinnamoyl) anthranilic acid (tranilast) prevents the synchronous upregulation of isoforms and receptors of the transforming growth factor (TGF)-beta system after arterial injury and reduces restenosis after human coronary angioplasty. However, the effects of tranilast and the importance of the TGF-beta system in stent restenosis, in which inward remodeling is unimportant but inflammatory cell stimulation of neointima formation is exaggerated, are uncertain. Boston minipigs, treated with tranilast or vehicle, were subjected to endoluminal stenting, and the expression of TGF-beta1 and TGF-beta3, the expression of their signaling receptors ALK-5 and TbetaR-II, leukocyte numbers around the stent struts, and neointima development were assessed over 28 days. Stenting greatly increased early (5-day) mRNA expression of the 2 TGF-beta isoforms and their receptors. Immunohistochemical localization later showed that their concentrations were greatest in regions adjacent to stent struts, where leukocytes and collagen deposition were prevalent. Tranilast suppressed these elevations in TGF-beta mRNAs and reduced their immunoreactive peptides detectable around stent struts. The accumulation of leukocytes and deposition of collagen in these regions was also greatly inhibited by tranilast. These effects were associated with a 48% reduction in maximal neointimal cross-sectional area and 43% reduction in mean neointimal cross-sectional area at 28 days (P<0.05). We conclude that tranilast suppresses neointima development after stenting, effects that can be at least partly attributed to its ability to attenuate the induction of the TGF-beta system and leukocyte accumulation around stent struts.


Detection of numerical chromosomal abnormalities in epithelial ovarian neoplasms by fluorescence in situ hybridization (FISH) and a review of the current literature.
Preliminary retrospective chromosomal analysis was performed using fluorescence in situ hybridization (FISH) with alphoid DNA probes for chromosomes 1, 3, 6, 8, 12, 17, and X. Twenty-four epithelial ovarian tumors were examined in this pilot study, including 8 borderline (LMP) serous tumors, 9 serous carcinoma, and 7 mucinous carcinoma. Hybridization signals were counted to demonstrate the frequency of aneusomy, trace chromosomal progression, and identify the predominance of chromosome copy number abnormalities that are specific to a particular histotype. The preliminary results revealed almost an equal number of mean aneusomies in serous (58.13 +/- 13%) and mucinous (64.33 +/- 10%) carcinoma, both of which were slightly higher than borderline serous tumors (50.57 +/- 17%). Hyposomies 3 and X were significantly higher in mucinous than in serous ovarian carcinomas, and lowest in borderline serous tumors (P<0.05 and P<0.01). Signal losses were a more frequent abnormality in all three histologic subtypes. Mucinous carcinomas showed a loss of chromosomes 8 (45.00 +/- 28%) and 3 (43.14 +/- 16%), in addition to a loss of chromosome X (56.29 +/- 12%). Serous carcinomas showed a gain of chromosome 1 (39.44 +/- 32%), followed by losses of chromosomes 6 (37.00 +/- 20%), 17 (36.44 +/- 19%), and 8 (36.89 +/- 19%). In borderline serous tumors, the most frequent findings were losses of chromosomes 6 (38.00 +/- 17%), 12 (36.88 +/- 17%), and 3 (36.13 +/- 21%). However, further research is necessary to substantiate these preliminary results and elucidate their clinical significance. A brief review of the literature pertaining to interphase cytogenetics in ovarian epithelial tumors is discussed also.


Atmospheric mercury accumulation rates between 5900 and 800 calibrated years BP in the High Arctic of Canada recorded by peat hummocks.
In this paper, we present the first comprehensive long-term record of preanthropogenic rates of atmospheric mercury accumulation in dated peat deposits for the High Arctic of Canada. Geochemical studies of two peat hummocks from Bathurst Island, Nunavut reveal substantial inputs from soil dust (titanium), marine aerosols (bromine), and mineral-water interactions (uranium). Mercury, however, was supplied to these peat mounds exclusively by atmospheric deposition. Mercury concentration measurements and age dating of the peat profiles indicate rather constant natural "background" mercury flux of ca. 1 microgram per square meter per year from 5900 to 800 calibrated years BP. These values are well within the range of the mercury fluxes reported from other Arctic locations, but also by peat cores from southern Canada that provide a record of atmospheric Hg accumulation extending back 8000 years. Thus, preanthropogenic Hg fluxes in the Arctic were not significantly different from atmospheric Hg fluxes in the temperate zone. In preindustrial times, therefore, the High Arctic was no more important as a sink for global atmospheric mercury than was the temperate zone.


Familial history of migraine influences habituation of visual evoked potentials.
Background Lack of habituation of visual evoked potentials (VEP) is a common finding in migraine patients between attacks. Previous studies have suggested an electrophysiological familial aggregation pattern associated with migraine. The aim of this study was to evaluate the influence of a positive familial history of migraine on VEP amplitude and habituation. Methods We recorded six blocks of 100 VEP during continuous pattern-reversal stimulation in 30 patients with migraine between attacks (MO) and in 30 healthy volunteers, of whom 15 had a first-degree relative suffering from migraine (HVm) and 15 had not (HV). Results Both MO and HVm had a significant deficit of VEP habituation and similarly reduced N1-P1 first block amplitudes, compared to HV (habituation slope: MO = 0.033, HVm = 0.021, HV = -0.025, HV vs. MO p = 0.002, HV vs. HVm p = 0.036; mean N1-P1 amplitude in the first block: MO = 9.08 µV, HVm = 9.29 µV, HV = 12.19 µV. HV vs. MO p = 0.041, HV vs. HVm p = 0.076). The first block N1-P1 amplitude was negatively correlated with the habituation slope for both MO (ρ = -.44, p = 0.015) and HVm (ρ = -.56, p = 0.031) while no significant correlation was found in HV (ρ = .17, p = 0.53). There were no differences in VEP latencies between the groups. Conclusions Our study suggests that lack of habituation of visual evoked potentials is probably a genetically determined endophenotypic trait that is associated with both migraine and migraine susceptibility. We hypothesize that genetic diversity of populations could account for some of the discrepancies between electrophysiological studies performed in migraine and for interindividual variations among the subgroups.


Supervised Learning in Adaptive DNA Strand Displacement Networks.
The development of engineered biochemical circuits that exhibit adaptive behavior is a key goal of synthetic biology and molecular computing. Such circuits could be used for long-term monitoring and control of biochemical systems, for instance, to prevent disease or to enable the development of artificial life. In this article, we present a framework for developing adaptive molecular circuits using buffered DNA strand displacement networks, which extend existing DNA strand displacement circuit architectures to enable straightforward storage and modification of behavioral parameters. As a proof of concept, we use this framework to design and simulate a DNA circuit for supervised learning of a class of linear functions by stochastic gradient descent. This work highlights the potential of buffered DNA strand displacement as a powerful circuit architecture for implementing adaptive molecular systems.


Differential incorporation of 13C label from dietary glucose into neutral sugars of rat intestine macromolecules.
Using gas chromatography-isotope ratio mass spectrometry, the detection, with a good reproducibility and in a single step, of the 13C content of glycoprotein neutral sugars, glycogen glucose, and ribonucleic acid ribose allowed us to trace incorporation into intestinal macromolecules of sugars derived from dietary glucose, labeled either naturally (as corn starch) or artificially. The 13C enrichment of glycoprotein neutral sugars was strong and rapid and plateaued up to the end of the experiment, whereas the 13C content of ribose increased linearly with time. By contrast, with artificially enriched dietary glucose, no significant 13C enrichment was detected in glycogen, suggesting that this macromolecule does not directly derive from dietary glucose. These results suggest differential control of sugars involved in the synthesis of intestinal macromolecules and demonstrate that this technique would be sensitive and reliable enough to be applied in man for serum glycoprotein sugar determinations.


Illness experiences and health recovery behaviors of patients in southern Appalachia.
The purpose of this exploratory study was to gain a better understanding of the influences of Appalachian culture and rural living on illness experiences and health recovery behaviors. The study sample consisted of 257 randomly selected adult patients admitted to medical-surgical units in eight hospitals in West Virginia. Patients completed interviews in the hospital and by phone and in their homes 1 month after hospital discharge. In addition, 203 nurses and 79 physicians completed a values survey and decisional control questions. The triangulation of quantitative and qualitative data suggested that culture, age, gender, and rural residence affected responses to illness and recovery. Traditional values and roles persisted in this population and influenced health behaviors. The findings of this study support the need for culturally sensitive care and for innovative education programs to reduce health risks.


[Basic research on digital logistic management of hospital].
This paper analyzes and explores the possibilities of digital information-based management realized by equipment department, general services department, supply room and other material flow departments in different hospitals in order to optimize the procedures of information-based asset management. There are various analytical methods of medical supplies business models, providing analytical data for correct decisions made by departments and leaders of hospital and the governing authorities.


Prognostic value of microvessel density and its correlation with clinicopathological features in human olfactory neuroblastoma.
Although angiogenesis plays an important role in tumor growth and invasion, its role in the progression of olfactory neuroblastoma (ONB) has rarely been published. The aim of the present research was to analyze the prognostic role of microvessel density (MVD) in ONB and its association with clinicopathological parameters. 70 ONB cases were assessed for immunohistochemical expression of CD31, CD34, CD105, VEGF, and VEGFR2. The expression of CD105-MVD was negatively associated with histological grade and tumor Kadish stage, and its expression was positively correlated with the expression of VEGF/VEGFR2. Low expression of CD105-MVD and high tumor histological grade were strongly associated with poor survival. Thus, CD105-MVD was demonstrated to be a valuable independent prognostic indicator for ONB. MVD is expected to be useful as an important marker to distinguish tumor histological grade.


Antioxidant activity of Sanionia uncinata, a polar moss species from King George Island, Antarctica.
Antioxidant agents counter reactive oxygen species (ROS) and can be used in cosmetic and medicinal applications. The goal of this study was to evaluate the antioxidant activity of an Antarctic moss species from King George Island (Antarctica), tentatively designated as KSJ-M5. On the basis of morphological characteristics, KSJ-M5 was identified as Sanionia uncinata (Hedw.) Loeske (Amblystegiaceae). The identification was confirmed by comparing the partial sequence of the ITS (internal transcribed spacer) region with that in GenBank. The antioxidant activity of an ethanol extract of KSJ-M5 was evaluated by analyzing its reducing power, superoxide scavenging activity, ABTS [2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)] cation scavenging activity, and DPPH (1,1-diphenyl-2-picrylhydrazyl) free-radical scavenging activity. The reducing power of 1 mg of KSJ-M5 extract was equivalent to 31.9 +/- 0.9 microg (Mean +/- SD, n = 3) of the commercial standard, BHT (butylated hydroxytoluene). IC(50) values of the KSJ-M5 extract for DPPH free-radical scavenging activity, superoxide scavenging activity, and ABTS cation scavenging activity were found as 356 +/- 26.8 microg/mL, 466.2 +/- 43.4 microg/mL, and 181.3 +/- 12.2 microg/mL, respectively. The total phenolic content in 1 mg of KSJM5 extract was equivalent to 12.7 +/- 2.7 microg of pyrocatechol. These results clearly showed that KSJ-M5 could be an important source of natural antioxidant agents for improved medicinal and cosmetic applications.


Chiral allene-containing phosphines in asymmetric catalysis.
We demonstrate that allenes, chiral 1,2-dienes, appended with basic functionality can serve as ligands for transition metals. We describe an allene-containing bisphosphine that, when coordinated to Rh(I), promotes the asymmetric addition of arylboronic acids to α-keto esters with high enantioselectivity. Solution and solid-state structural analysis reveals that one olefin of the allene can coordinate to transition metals, generating bi- and tridentate ligands.


Pain insensitivity in schizophrenia. Case report and review of the literature.
We describe a schizophrenic man whose lack of pain and related objective signs of a perforated small bowel led to a delay in diagnosis and surgical intervention. A review of the literature suggests that both psychodynamic and specific biologic factors can produce atypical presentations in psychotic patients with illnesses in which pain is characteristically a prominent presenting symptom. While research into the cause of altered pain perception in psychotic patients is continuing, clinicians should maintain a high index of suspicion of serious medical illness when evaluating such patients.


Heparanase overexpression reduces carrageenan-induced mechanical and cold hypersensitivity in mice.
Heparanase controls the structure and functions of extracellular matrix (ECM) by degrading heparan sulfate proteoglycans. Heparanase is involved in inflammatory process through modulating the functions of inflammatory cytokines. The present study aimed to find out whether overexpression of heparanase in mice affects carrageenan-induced localized inflammation and inflammatory hyperalgesia. Without challenge, the heparanase overexpression did not significantly affect the mice in response to mechanical, cold and heat stimulation. Unilateral subcutaneous administration of carrageenan produced hypersensitivity to mechanical and cold in both wildtype and the heparanase overexpression (Hpa-tg) mice 24h after treatment. In comparison to wildtype animals, the Hpa-tg mice showed significantly reduced mechanical and cold hypersensitivity. This may, at least partially, due to the reduced mast cell infiltration at the site of inflammation in Hpa-tg mice. These data support a role for heparanase that reduces localized inflammation and inflammatory hyperalgesia in mice.


Steady-state pharmacokinetics of a double-boosting regimen of saquinavir soft gel plus lopinavir plus minidose ritonavir in human immunodeficiency virus-infected adults.
Management of treatment-experienced human immunodeficiency virus patients has become complex, and therapy may need to include two protease inhibitors at therapeutic doses. The objective of this study was to characterize the pharmacokinetics in serum of saquinavir (1,000 mg twice daily [b.i.d.]), lopinavir (400 mg b.i.d.), and ritonavir (100 mg b.i.d.) in a multidrug rescue therapy study and to investigate whether steady-state pharmacokinetics of lopinavir-ritonavir are affected by coadministration of saquinavir. Forty patients were included (25 given ritonavir, lopinavir, and saquinavir and 15 given ritonavir and lopinavir). The median pharmacokinetic parameters of lopinavir were as follows: area under the concentration-time curve from 0 to 12 h (AUC(0-12)), 85.1 microg/ml . h; maximum concentration of drug in serum (C(max)), 10.0 microg/ml; trough concentration of drug in serum (C(trough)), 7.3 microg/ml; and minimum concentration of drug in serum (C(min)), 5.5 microg/ml. Lopinavir concentrations were similar in patients with and without saquinavir. The median pharmacokinetic parameters for saquinavir were as follows: AUC(0-12), 22.9 microg/ml . h; C(max), 2.9 microg/ml; C(trough), 1.6 microg/ml; and C(min), 1.4 microg/ml. There was a strong linear correlation between lopinavir and ritonavir and between saquinavir and ritonavir concentrations in plasma. The correlation between lopinavir and saquinavir levels was weaker. We found higher saquinavir concentrations in women than in men, with no difference in lopinavir levels. Only patients with very high body weight presented lopinavir and saquinavir concentrations lower than the overall group. Ritonavir has a double-boosting function for both lopinavir and saquinavir, and in terms of pharmacokinetics, the drug doses selected seemed appropriate for combining these agents in a dual protease inhibitor-based antiretroviral regimen for patients with several prior virologic failures.


Efficient method of evaluation for Gaussian Hartree-Fock exchange operator for Gau-PBE functional.
We previously developed an efficient screened hybrid functional called Gaussian-Perdew-Burke-Ernzerhof (Gau-PBE) [Song et al., J. Chem. Phys. 135, 071103 (2011)] for large molecules and extended systems, which is characterized by the usage of a Gaussian function as a modified Coulomb potential for the Hartree-Fock (HF) exchange. We found that the adoption of a Gaussian HF exchange operator considerably decreases the calculation time cost of periodic systems while improving the reproducibility of the bandgaps of semiconductors. We present a distance-based screening scheme here that is tailored for the Gaussian HF exchange integral that utilizes multipole expansion for the Gaussian two-electron integrals. We found a new multipole screening scheme helps to save the time cost for the HF exchange integration by efficiently decreasing the number of integrals of, specifically, the near field region without incurring substantial changes in total energy. In our assessment on the periodic systems of seven semiconductors, the Gau-PBE hybrid functional with a new screening scheme has 1.56 times the time cost of a pure functional while the previous Gau-PBE was 1.84 times and HSE06 was 3.34 times.


A national survey of characteristics of child advocacy centers in the United States: Do the flagship models match those in broader practice?
Child Advocacy Centers (CAC) emphasize developing effective cross-agency collaborations between workers involved in serious abuse investigations to foster improvements in agency outcomes, and to minimize distress, confusion and uncertainty for children and families. This study examined the characteristics of CACs, whether models in practice match the predominant model presented in the research literature. Directors of CACs in the United States that were members of the National Children's Alliance (NCA) mailing list (n=361) completed an online survey in 2016. While some core characteristics were ubiquitous across CACs, the data suggests that different types of CACs exist defined by characteristics that are not prescribed under NCA principles, but which are arguably relevant to the quality of the response. From the results of a cluster analysis, the researchers propose a typology of CACs that reflects the development and integration of centers: (a) core CAC services (i.e. interviewing & cross-agency case review); (b) an aggregator of external services, and (c) a more centralized full-service CAC. Further research is needed to understand how these variations may impact practice and outcomes; this is particularly important considering many CACs do not match the full-service models most commonly examined in the research literature, which limits the degree to which these findings apply to CACs generally. This article proposes further research framed by the need to better understand how different parts of the response impact on outcomes for children and families affected by abuse.


The role of flavin-containing monooxygenase (FMO) in the metabolism of tamoxifen and other tertiary amines.
Tamoxifen is utilized in breast cancer therapy and in chemoprevention. Tamoxifen may enhance risk for other neoplasias, especially endometrial cancer. The risk:benefit depends on the rate of metabolic activation versus detoxication. Cytochrome P450-dependent alpha-hydroxylation, followed by sulfonation, represents a metabolic activation pathway, producing products capable of covalent DNA adduction. In contrast, tamoxifen N-oxygenation represents a detoxication pathway, with the caveat that N-oxides can be reduced back to the parent amines. The N-oxygenation pathway will be the focus for this review. Dr. David Kupfer pioneered studies on cytochrome P450 and flavin-containing monooxygenase (FMO) tamoxifen metabolism. We collaborated with Dr. Kupfer's laboratory and recently determined that the low level of tamoxifen N-oxide production in human liver microsomes may be explained by the kinetics of FMO1 versus FMO3.


Prognostic value of residual cancer burden and Miller-Payne system after neoadjuvant chemotherapy for breast cancer.
To verify the feasibility of using the residual cancer burden (RCB) index to stratify prognosis of patients after neoadjuvant chemotherapy (NAC) and to compare RCB with the Miller-Payne system. We retrospectively analyzed clinicopathological data of patients receiving treatment between January 1, 2010 and December 31, 2018. Kaplan-Meier curves were used to compare the survival outcomes and estimate disease-free survival (DFS) and disease-specific survival (DSS). Harrell's concordance index (C-index) was used to evaluate the predictive accuracy of RCB and Miller-Payne system. A total of 423 female patients with complete data were included in the analysis, with a median follow-up time of 58.5 months (range, 7-126 months); 84 patients experienced recurrence, and 48 experienced breast cancer related death. RCB index and the Miller-Payne system were associated with prognosis in the whole cohort. Patients who achieved RCB-I had similar survival outcomes as those with pathological complete response (pCR, RCB-0). In whole cohort, for the RCB index and the Miller-Payne system, respectively, C-indexes for DFS were 0.73 and 0.64, for DSS were 0.74 and 0.64. The average RCB score was different among three subtypes (F=9.335, P<0.001). The RCB index and the Miller-Payne system can stratify survival outcome of patients after NAC, and RCB had a superior prediction accuracy, especially for triple-negative breast cancer (TNBC). New cut-off value should be sought in order to improve prediction accuracy.


[Radiotherapy, chemotherapy and target therapy for treatment of head and neck cancer : new developments].
Approximately 60% of patients initially treated for squamous cell cancer of the upper gastrointestinal tract suffer from advanced tumor disease (UICC stages III and IV). Multimodal strategies lead to overall survival rates of up to 50%. Recent studies show indications that the risk of distant metastases after induction chemotherapy (CT) is less than after primary radiotherapy (RT) or radiochemotherapy (RCT). Hyperfractionation or accelerated radiation with concomitant boost shows superior results compared to classic RT. Intensity-modulated radiotherapy (IMRT) is a new method for better adjusted dose distribution. Targeted therapy with specific antibodies against biological targets, such as epidermal growth factor receptor (EGFR), showed superiority over RT but the comparison to classic RCT is still pending. Targeted therapy against vascular endothelial growth factor (VEGR) showed antiangiogenetic effects on tumors. In cases of non-resectability or distant metastases, palliative CT and target therapy are recommended. Reirradiation or IMRT offer increased locoregional tumor control at the expense of higher toxicity. Overall, advances in research on tumor biology offer increasingly more prognostic factors and markers for customized individual targeted therapy and CT.


Profile of diabetic ketoacidosis at a teaching hospital in Benghazi, Libyan Arab Jamahiriya.
This study describes the profile of 100 cases of diabetic ketoacidosis (DKA) at a teaching hospital in 1 Benghazi, Libyan Arab Jamahiriya. DKA was more frequent in young women with type 1 diabetes and mostly due to preventable causes, e.g., disrupted insulin treatment and/or infection. DKA also occurred in type 2 diabetics, with a higher mortality rate, as they were older patients with co-morbidity. Polyurea, fatigue, abdominal pain and vomiting were the most common clinical features, while coma was rarer. A high number of cases were first presentations of type 1 diabetes; hence this diagnosis should be considered in all patients with acute abdomen or decreased level of consciousness. The reasons for high mortality rate in this study (10%) were multifactorial.


Proxies to monitor the inactivation of viruses by ozone in surface water and wastewater effluent.
Ozone treatment is an effective barrier against viral pathogens, wherefore it is an integral part of many water and wastewater treatment trains. However, the efficacy of ozone treatment remains difficult to monitor, due to the lack of methods to track virus inactivation in real-time. The goal of this work was to identify easy-to-measure proxies to monitor virus inactivation during water and wastewater treatment by ozone. Proxies considered were the abatement in UV absorbance at 254 nm (UV254) and carbamazepine (CBZ), a ubiquitous organic micropollutant with a similar abatement rate constant as human viruses. The proxies, as well as the inactivation of two viruses (MS2 coliphage and coxsackievirus B5) were measured in surface water and in a secondary wastewater effluent as a function of the specific ozone dose (mgO3/mg dissolved organic carbon). Virus inactivation was rapid in both matrices, but was more efficient in surface water. This trend was also evident when inactivation was assessed as a function of the ozone exposure to account for the different ozone demand of the two water types. Both proxies, as well as the specific ozone dose, were correlated with virus inactivation. The correlations depended only weakly on the virus species, but - with the exception of CBZ abatement - differed between the two water types. Finally, predictive relationships were established using Bayesian power models, to estimate virus inactivation based on the measurement of a proxy. The models were then applied to estimate the MS2 inactivation in a pilot-scale ozone reactor that treats surface water of Lake Zurich. All proxies yielded good estimates of the actual MS2 inactivation in the pilot plant, indicating that the proxy-inactivation relationships established in the laboratory can also be applied to flow-through reactors. This study confirms that ozone is a highly effective disinfectant for viruses in both surface water and wastewater, and that the abatement of UV254 and CBZ can be used to track virus inactivation during water and wastewater treatment.


Resveratrol inhibits proliferation and induces apoptosis of nasopharyngeal carcinoma cell line C666-1 through AMPK activation.
Resveratrol, a natural phenolic compound found in red grapes, has been reported to inhibit proliferation and induce apoptosis via regulation of AMPK signaling pathways in several cancer cell types. However, little is known about the effect of resveratrol on the human Nasopharyngeal carcinoma (NPC) cell line C666-1. Moreover, the molecular mechanisms of resveratrol-mediated apoptosis in C666-1 cells remain to be clarified. Cell proliferation was measured by CCK8 assay, cell apoptosis rate was evaluated by flow cytometric analysis, and the protein expression alterations of AMPK signaling pathways were detected by Western blotting. Treatment of resveratrol inhibited cell viability and promote apoptosis of C666-1 cells. In addition, we showed that resveratrol could also activate caspase-3 and alter the Bax/Bcl-2 apoptotic signaling. Furthermore, all these changes may be due to the activation of AMPK activity by resveratrol treatment, and we also found that the p70S6K and s6 activities, downstream factors of AMPK, were also blocked by resveratrol. Our results revealed that resveratrol can be regarded as a new effective and chemopreventive compound for human NPC treatment.


Insight into the polar reactivity of the onium chalcogen analogues of S-adenosyl-L-methionine.
S-Adenosyl-L-methionine (AdoMet) is one of Nature's most diverse metabolites, used not only in a large number of biological reactions but amenable to several different modes of reactivity. The types of transformations in which it is involved include decarboxylation, electrophilic addition to any of the three carbons bonded to the central sulfur atom, proton removal at carbons adjacent to the sulfonium, and reductive cleavage to generate 5'-deoxyadenosyl 5'-radical intermediates. At physiological pH and temperature, AdoMet is subject to three spontaneous degradation pathways, the first of which is racemization of the chiral sulfonium group, which takes place in a pH-independent manner. The two remaining pathways are pH-dependent and include (1) intramolecular attack of the alpha-carboxylate group onto the gamma-carbon, affording L-homoserine lactone (HSL) and 5'-methylthioadenosine (MTA), and (2) deprotonation at C-5', initiating a cascade that results in formation of adenine and S-ribosylmethionine. Herein, we describe pH-dependent stability studies of AdoMet and its selenium and tellurium analogues, Se-adenosyl-L-selenomethionine and Te-adenosyl-L-telluromethionine (SeAdoMet and TeAdoMet, respectively), at 37 degrees C and constant ionic strength, which we use as a probe of their relative intrinsic reactivities. We find that with AdoMet intramolecular nucleophilic attack to afford HSL and MTA exhibits a pH-rate profile having two titratable groups with apparent pK(a) values of 1.2 +/- 0.4 and 8.2 +/- 0.05 and displaying first-order rate constants of <0.7 x 10(-6) s(-1) at pH values less than 0.5, approximately 3 x 10(-6) s(-1) at pH values between 2 and 7, and approximately 15 x 10(-6) s(-1) at pH values greater than 9. Degradation via deprotonation at C-5' follows a pH-rate profile having one titratable group with an apparent pK(a) value of approximately 11.5. The selenium analogue decays significantly faster via intramolecular nucleophilic attack, also exhibiting a pH-rate profile with two titratable groups with pK(a) values of approximately 0.86 and 8.0 +/- 0.1 with first-order rate constants of <7 x 10(-6) s(-1) at pH values less than 0.9, approximately 32 x 10(-6) s(-1) at pH values between 2 and 7, and approximately 170 x 10(-6) s(-1) at pH values greater than 9. Degradation via deprotonation at C-5' proceeds with one titratable group displaying an apparent pK(a) value of approximately 14.1. Unexpectedly, TeAdoMet did not decay at an observable rate via either of these two pathways. Last, enzymatically synthesized AdoMet was found to racemize at rates that were consistent with earlier studies (Hoffman, J. L. (1986) Biochemistry 25, 4444-4449); however, SeAdoMet and TeAdoMet did not racemize at detectable rates. In the accompanying paper, we use the information obtained in these model studies to probe the mechanism of cyclopropane fatty acid synthase via use of the onium chalcogens of AdoMet as methyl donors.


Comparison of adrenocorticotropin control in Brattleboro, Long-Evans, and Wistar rats. Measurement of corticotropin-releasing factor, arginine vasopressin, and oxytocin in hypophysial portal blood.
The purpose of this study was to compare the control of adrenocorticotropin (ACTH) and corticosterone secretion in homozygous Brattleboro rats with their syngeneic controls, Long-Evans rats, and with rats of the Wistar strain. Plasma concentrations of ACTH and corticosterone were measured by radioimmunoassay in trunk blood, and corticotropin-releasing factor 41 (CRF-41), arginine vasopressin (AVP), and oxytocin were assayed in hypophysial portal vessel blood. Portal plasma was extracted with methanol for CRF-41 determination, and four different antisera and several different high-performance liquid chromatography (HPLC) systems were used to investigate AVP release. The peripheral plasma concentrations of ACTH and corticosterone were significantly higher in Long-Evans and homozygous Brattleboro than in Wistar rats. This difference was due, at least in part, to an approximately twofold greater release of CRF-41 into hypophysial portal blood of the Long-Evans and Brattleboro compared with Wistar rats. There was no significant difference between the strains in the output of oxytocin into portal blood. While no AVP could be detected in the neural lobe of homozygous Brattleboro rats, a small amount of AVP-like immunoreactivity was detected in unextracted hypophysial portal blood from homozygous Brattleboro rats. However, this AVP-like immunoreactivity was clearly distinct from authentic AVP in several HPLC systems, had no antidiuretic activity, and on gel filtration had a relative molecular mass greater than 5 kD. In contrast, the AVP-like immunoreactivity in hypophysial portal blood from Long-Evans rats co-eluted with authentic AVP in all HPLC systems tested.(ABSTRACT TRUNCATED AT 250 WORDS)


Cp*Rh(III)-Catalyzed Regioselective C(sp2)-H Mono- and Dialkynylation of Thioamides by Sulfur Coordination.
An efficient Cp*Rh(III)-catalyzed regioselective C(sp2)-H mono- and dialkynylation of thioamides was described. This reaction was performed under mild conditions in high yields (up to 98%) with a broad substrate scope. Significantly, the versatility of this method was further demonstrated by controlled mono- and dialkynylation. Application of this protocol in the late stage functionalization of two drug molecules (Adapalene and Amoxapine) was also demonstrated.


Regulation of leptin and leptin receptor in baboon pregnancy: effects of advancing gestation and fetectomy.
Leptin, a product of both adipose tissue and the placental syncytiotrophoblast and a potential regulator of primate conceptus development, increases in the maternal circulation with advancing gestation. This increase may be potentiated by estrogens, which also increase as pregnancy progresses. In the present study adipose tissue was collected from nonpregnant (n = 5) baboons (Papio sp) and in baboons during early (days 58-62; n = 5), mid (days 98--102; n = 5), and late (days 158-162; n = 5) pregnancy (term, approximately 184 days). Additionally, placental estrogen production was inhibited in pregnant baboons by the removal of fetal androgen precursors via fetectomy at midgestation, with tissues collected from fetectomized (n = 5) baboons approximately 60 days later. Leptin, estrogens, and androgens were quantitated in maternal serum by RIA. Leptin (LEP) and leptin receptor (LEP-R(L) and LEP-R(S) isoforms) messenger ribonucleic acids (mRNAs) were quantitated by competitive RT-PCR, and leptin concentrations were determined by RIA in maternal adipose and placental villous tissues. Although LEP transcript abundance in adipose tissues was unchanged as a result of pregnancy or with advancing gestation, the leptin protein level was higher (P < 0.02) in pregnant baboons in early gestation than in nonpregnant baboons and increased with gestational age (P < 0.04). Maternal serum estrogens (estradiol and estrone) and androgens (androstenedione and testosterone) were lower (P < 0.0001) in fetectomized baboons than in intact controls. Serum leptin concentrations were unchanged by fetectomy, but the abundance of LEP mRNA transcripts was lower (P < 0.003) in sc adipose tissue and 3-fold higher (P < 0.05) in placenta. Similarly, the leptin protein level declined (P < 0.05) in sc adipose tissue and increased (P < 0.05) in placenta in fetectomized baboons. Although LEP-R(L) mRNA levels were unchanged after fetectomy, placental LEP-R(S) transcript abundance was lower (P < 0.04) than in pregnancy-intact baboons matched for gestational age. Results suggest that both adipose tissue and the placenta may contribute to maternal hyperleptinemia during normal primate pregnancy. Furthermore, the withdrawal of placental steroids results in the enhanced placental leptin production that is commensurate with a decline in production by sc adipose tissue.


Computerized slide show for the 1990s lecturer.
One of the most difficult and time-consuming tasks of writing and presenting papers is the review and coordination of patient photographic records. For years, not only has the 35-mm slide been the means of photographic storage for patient records, but also the standard for illustrating lectures and presentations. This current method is cumbersome and time consuming. We have used existing software of the Cameo II and imaging system to prepare, create, and present illustrations for lectures. Patient images are digitalized from any source (eg, photographs, slides, video tape) and electronically stored in the computer along with the computer-generated illustrations. When a lecture is prepared, the images are arranged sequentially in an electronic carousel. This computerized program is recorded on video tape and simply played through the video projector during the presentation to display the images. This system is more efficient since any stored image can be displayed instantaneously in any order without the handling of 35-mm slides. The only limitation of this system is the user's imagination. As the current trend in computer technology continues with high-resolution TV and video systems, the 35-mm slide presentation will become obsolete.


[Participation of the opioid-ergic system in the regulation of afferent reactions of the damaged myocardium].
It has been established that in lesion of the myocardium accumulation of huge amount of algesic compounds may cause limitation of the level of cardiac afferentation. Use of naloxone, buterfanol tartrate and D-ala-2-lei-enkephalin prevent the development of the reaction. The possibility of participation of the endogenic cardiac opioids in anti-nociceptive reactions of heart during its lesion is considered.


CyclinD-CDK4/6 complexes phosphorylate CDC25A and regulate its stability.
The phosphatase CDC25A is a key regulator of cell cycle progression by dephosphorylating and activating cyclin-CDK complexes. CDC25A is an unstable protein expressed from G1 until mitosis. CDC25A overexpression, which can be caused by stabilization of the protein, accelerates the G1/S and G2/M transitions, leading to genomic instability and promoting tumorigenesis. Thus, controlling CDC25A protein levels by regulating its stability is a critical mechanism for timing cell cycle progression and to maintain genomic integrity. Herein, we show that CDC25A is phosphorylated on Ser40 throughout the cell cycle and that this phosphorylation is established during the progression from G1 to S phase. We demonstrate that CyclinD-CDK4/CDK6 complexes mediate the phosphorylation of CDC25A on Ser40 during G1 and that these complexes directly phosphorylate this residue in vitro. Importantly, we also find that CyclinD1-CDK4 decreases CDC25A stability in a ßTrCP-dependent manner and that Ser40 and Ser88 phosphorylations contribute to this regulation. Thus our results identify cyclinD-CDK4/6 complexes as novel regulators of CDC25A stability during G1 phase, generating a negative feedback loop allowing control of the G1/S transition.


A Lipoxygenase Pathway Is Activated in Rice after Infection with the Rice Blast Fungus Magnaporthe grisea.
Lipoxygenase (LOX) and lipid hydroperoxide-decomposing activity (LHDA) markedly increased in the fifth leaves of rice (Oryza sativa cv Aichiasahi) after infection with the rice blast fungus, Magnaporthe grisea. The increases in the enzyme activities were significantly higher in response to infection with an incompatible strain (race 131) compared with infection with a compatible strain (race 007) of the fungus. Using ion-exchange chromatography, we isolated three LOX activities (leaf LOX-1, -2, -3) from both uninoculated and infected leaves. The activity of leaf LOX-3, in particular, increased in the incompatible race-infected leaves. The leaf LOX-3 had a pH optimum of 5.0 and produced preferentially 13-l-hydroperoxy-9,11 (Z,E)-octadecadienoic acid (13-HPODD) from linoleic acid. 13-HPODD and 13-l-hydroxy-9,11 (Z,E)-octadecadienoic acid, one of the reaction products from 13-HPODD by LHDA, were highly inhibitory to the germination of conidia of the fungus. The present study provides correlative evidence for important roles of LOX and LHDA in the resistance response of rice against the blast fungus.


Ischemic preconditioning improved renal ischemia/reperfusion injury and hyperglycemia.
Renal ischemia/reperfusion (I/R) is an alternation of renal hemodynamics, which results in diverse postischemic responses and eventually acute kidney injury. Although renal ischemic preconditioning (IPC) is known to protect the kidney from I/R injury, the precise renoprotective mechanisms are not completely understood. The multiple renoprotective effects of IPC underscore the importance in understanding molecular mechanisms and the targets of action involved. This study aimed to identify the biochemical changes in renal I/R injury and investigate the renoprotective mechanisms of IPC. Herein, renal I/R was produced in adult male Sprague-Dawley rats through the bilateral ligation of renal pedicles for 45 min, followed by reperfusion for 24 h. For the IPC group, rats were subjected to three cycles of 2-min ischemia, followed by a 5-min reperfusion, 15 min prior to renal I/R. Our data confirmed the beneficial effects that IPC has on renal I/R injury. IPC-mediated renoprotection was associated with the resolution of oxidative stress, inflammation, apoptosis, and hyperglycemia. Among the numerous signaling molecules involved in the renoprotective mechanisms of IPC, an elevated protein expression of Nrf2, HO-1, LC3 II conversion, along with Atg12 and protein phosphorylation of AMPK, as well as a decreased protein phosphorylation of ERK, p38 MAPK, and Akt and NF-κB DNA binding activity were identified. Importantly, the post renal I/R overproduction of counter-regulatory hormones, impaired hepatic insulin action, and augmented hepatic gluconeogenesis were improved through IPC. As counter-regulatory hormones have been implicated in the induction of oxidative stress, inflammation, apoptosis, impaired insulin action, hyperglycemia, and tissue destruction, our findings suggest that counter-regulatory hormones may well be valuable targets of IPC for combatting renal I/R injury. © 2018 IUBMB Life, 71(3):321-329, 2019.


Generating evidence on screening, diagnosis and management of non-communicable diseases during pregnancy; a scoping review of current gap and practice in India with a comparison of Asian context.
Children born to high-risk pregnancies are more likely to experience adverse health outcomes later in life. As estimated, 15% of all pregnancies are at risk of various life-threatening conditions leading to adverse maternal and foetal outcomes. Millennium Development Goal resulted in the global reduction of maternal death from 390,000 to 275000 in 1990-2015). Similarly, to keep this momentum, the current United Nations Sustainable Development Goal (SDG: 3.1) aims at reducing the global maternal mortality ratio to less than 70 per 100,000 live births by 2030, and this can be achieved by addressing high-risk pregnancy contributing to significant mortality and morbidity. In India, gestational diabetes, gestational hypertension, and gestational hypothyroidism were identified as factors contributing to the high-risk pregnancy. This review summarises the commonly used approach for screening, diagnosis, and management of these conditions in the Asian population. It draws a comparison with the current protocols and guidelines in the Indian setting. Electronic search in PubMed and Google Scholar, reference snowballing, and review of current guidelines and protocols were done between January 2010 to October 2019. Published studies reporting Screening, diagnosis, and management of these conditions were included. Articles selected were then screened, appraised for quality, extract relevant data, and synthesised. Screening, diagnosis, and management of these three conditions vary and no single universally accepted criteria for diagnosis and management exist to date. In India, national guidelines available have not been evaluated for feasibility of implementation at the community level. There are no national guidelines for PIH diagnosis and management despite the increasing burden and contribution to maternal and perinatal morbidity and mortality. Criteria for diagnosis and management of gestational diabetes, gestational hypertension, and gestational hypothyroidism varies but overall early screening for predicting risk, as reported from majority of the articles, were effective in minimizing maternal and foetal outcome. Existing National guidelines for Screening, Diagnosis, and Management of Gestational Diabetes Mellitus (2018) and Gestational Hypothyroidism (2014) need to be contextualized and modified based on the need of the local population for effective treatment. Findings from this review show that early screening for predicting risk to be an effective preventive strategy. However, reports related to a definitive diagnosis and medical management were heterogeneous.


Long-Lasting Impairments in Quadriceps Mitochondrial Health, Muscle Size, and Phenotypic Composition Are Present After Non-invasive Anterior Cruciate Ligament Injury.
Despite rigorous rehabilitation aimed at restoring muscle health, anterior cruciate ligament (ACL) injury is often hallmarked by significant long-term quadriceps muscle weakness. Derangements in mitochondrial function are a common feature of various atrophying conditions, yet it is unclear to what extent mitochondria are involved in the detrimental sequela of quadriceps dysfunction after ACL injury. Using a preclinical, non-invasive ACL injury rodent model, our objective was to explore the direct effect of an isolated ACL injury on mitochondrial function, muscle atrophy, and muscle phenotypic transitions. A total of 40 male and female, Long Evans rats (16-week-old) were exposed to non-invasive ACL injury, while 8 additional rats served as controls. Rats were euthanized at 3, 7, 14, 28, and 56 days after ACL injury, and vastus lateralis muscles were extracted to measure the mitochondrial respiratory control ratio (RCR; state 3 respiration/state 4 respiration), mitochondrial reactive oxygen species (ROS) production, fiber cross sectional area (CSA), and fiber phenotyping. Alterations in mitochondrial function and ROS production were detected using two-way (sex:group) analyses of variance. To determine if mitochondrial characteristics were related to fiber atrophy, individual linear mixed effect models were run by sex. Mitochondria-derived ROS increased from days 7 to 56 after ACL injury (30-100%, P < 0.05), concomitant with a twofold reduction in RCR (P < 0.05). Post-injury, male rats displayed decreases in fiber CSA (days 7, 14, 56; P < 0.05), loss of IIa fibers (day 7; P < 0.05), and an increase in IIb fibers (day 7; P < 0.05), while females displayed no changes in CSA or phenotyping (P > 0.05). Males displayed a positive relationship between state 3 respiration and CSA at days 14 and 56 (P < 0.05), while females only displayed a similar trend at day 14 (P = 0.05). Long-lasting impairments in quadriceps mitochondrial health are present after ACL injury and play a key role in the dysregulation of quadriceps muscle size and composition. Our preclinical data indicate that using mitoprotective therapies may be a potential therapeutic strategy to mitigate alterations in muscle size and characteristic after ACL injury.


Bis[μ(2)-1-(2-carb-oxy-benzo-yl)thio-semi-carbazide(3-)]hexa-pyridine-trinickel(II) pyridine monosolvate monohydrate.
The reaction of Ni(OAc)(2)·4H(2)O with 1-(2-carb-oxy-benzo-yl)thio-semicarbazide (H(3)L) produces the title complex, [Ni(3)(C(9)H(6)N(3)O(3)S)(2)(C(5)H(5)N)(6)]·C(5)H(5)N·2H(2)O, which contains an linear array of three Ni(II) atoms. The asymmetric unit contains half of the complex mol-ecule, a water mol-ecule and a half-mol-ecule of pyridine. The central Ni(II) atom, located on a crystallographic inversion centre, has an octa-hedral N(4)O(2) environment. The other two Ni(II) atoms have a square-pyramidal N(3)OS environment, each bridged to the central Ni(II) atom via the L(3-) group. The carboxyl-ate groups coordinate to the metal atoms in a monodentate fashion. The water mol-ecule is linked to the complex mol-ecule via O-H⋯O hydrogen bonds. The mol-ecules further assemble into a one-dimensional network parallel to [001] via inter-molecular N-H⋯O hydrogen bonds.


Outcome of infants with unrepaired heart disease admitted to the pediatric intensive care unit: single-center developing country perspective.
Congenital heart disease (CHD) has an incidence of ∼0.8-1%. Outcome of previously diagnosed CHD patients awaiting surgery (either correction or palliation) in a developing country setting is unknown. We strive to determine the outcome of patients with CHD awaiting surgery who present to pediatric intensive care unit (PICU) setting with an acute illness. Retrospective cross-sectional chart review. Pediatric intensive care unit of The Aga Khan University Hospital, Karachi, Pakistan. Medical records of infants (1-12 months) with CHD awaiting surgery presenting to the PICU with an acute illness between January 2009 and June 2012 were included. Newly diagnosed CHD patients, those not requiring PICU admission, and those transferred to another hospital were excluded. A total of 34 infants met the inclusion criteria. Median age at presentation was 5 months. Seventy-four percent of the infants had CHD lesion characterized by increased pulmonary blood flow (shunt lesions). Though none of the patients met the strict criteria for sepsis or pneumonia, 74% were admitted with a diagnosis of pneumonia or sepsis. Only 15% of patient had congestive heart failure as an admitting diagnosis. Oxygen therapy was given to 94% of these patients. Fifty-nine percent of these patients expired during the admission, 95% of those expired had multiorgan dysfunction. Patients with CHD awaiting surgery and who admitted to the PICU with acute illness are at high risk for mortality. Stringent criteria to diagnose pneumonia or sepsis should be used in these patients.


A two-stage protocol for verifying vital status in large historical cohort studies.
When access to the Social Security Administration's Master Death Claim File was restricted in the mid-1980s, researchers were left with no time- and cost-effective protocol for verifying the vital status of large historical cohorts. A two-stage tracing protocol was designed to overcome this restriction. Stage I relies on national-scale sources to focus on the complete and accurate identification of deaths among persons unconfirmed as alive and assumes that persons not identified as deceased are alive. Stage II tests the "alive" assumption by extensively tracing a random sample of cohort members with unconfirmed vital status. Stage II provides unbiased estimates of the proportion of deaths among the assumed "alives" in the cohort (misclassification rate) and the proportion of persons untraceable in the total cohort. This paper describes our two-stage protocol and an application to a large, ongoing occupational cohort study.


Disruptive visions.
A number of concepts have been advocated for the next generation operating room based on some inadequacies of the current systems. Most have focused on removing excess tubes and wiring, others on information systems or robotics. An analysis of other industries, a projected direction of current technologies, a focus on the importance of integrated information systems, and a serious consideration of emerging basic technologies suggest a significantly different approach.


Minimally manipulative extraction of polycystic cervical neurocysticercosis.
Intradural, extramedullary cervical spinal involvement is an uncommon manifestation of neurocysticercosis. A case of a middle-aged man with neurocysticercosis in the intradural extramedullary cervical spine and brain who originally presented with bilateral paresthesias of his extremities, with a progressively unsteady gait. Magnetic resonance imaging revealed cystic enhancing lesions in the brain and cervical region of the spine, with the largest cyst extending from the posterior fossa through C2, causing spinal cord compression. The patient underwent surgical resection of the intradural extramedullary cervical spinal lesions, and he has continued to improve clinically, with no recurrence of cystic lesions. When examining patients with clinical signs of a spinal mass lesion, the differential diagnosis should include neurocysticercosis of the spine.


Rearrangements of [C(6)H(7)Si](+) cations. A radiochemical and quantum chemical study.
Nucleogenic cations were formed by beta-decay of phenylsilane tritiated at ortho- and para-positions of the benzene ring as well as at the silyl group and the products of their reactions with methyl tert-butyl ether were analyzed by radiochromatography. We found that the o-silatolyl cation was isomerized into the silabenzyl cation while the p-silatolyl cation was not. Furthermore, the silabenzyl cation was not converted into other isomers. The potential energy surface of the C(6)H(7)Si(+) system was constructed by B3LYP and MP2 methods using an aug-cc-pVDZ basis set. Theory predicts the low barrier for o-silatolyl-silabenzyl isomerization but high barriers for hydride shifts in the ring from para to meta- to ortho-isomers. It seems that nascent nucleogenic ions have enough internal energy to overcome the ortho-to-benzyl barrier but not enough to cross over the hydride-shift barriers. Theory also confirms that the isomerization of the silabenzyl cation to the [C(6)H(6).SiH](+) complex takes place in one step with a 62 kcal mol(-1) barrier, whereas that to either the global minimum [C(6)H(7).Si](+) or the silatropylium ion involves multisteps with 69-80 kcal/mol barriers. In addition, we find that the barrier of interconversion between the [C(6)H(6).SiH](+) complex and one of the low-lying [C(6)H(7).Si](+) complexes is only 29 kcal/mol.


MicroRNA.
MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene-expression posttranscriptionally. MiRNA research in allergy is expanding because miRNAs are crucial regulators of gene expression and promising candidates for biomarker development. MiRNA mimics and miRNA inhibitors currently in preclinical development have shown promise as novel therapeutic agents. Multiple technological platforms have been developed for miRNA isolation, miRNA quantitation, miRNA profiling, miRNA target detection, and modulating miRNA levels in vitro and in vivo. Here we will review the major technological platforms with consideration given for the advantages and disadvantages of each platform.


Comparisons of atropine versus cyclopentolate cycloplegia in myopic children.
In clinical practice, 1% atropine and 1% cyclopentolate are used as cycloplegia agents to diagnose refractive error. The influence of 1% atropine on ocular biometry is obscure, and the impact of 1% cyclopentolate remains controversial. This study aims to compare the effects of atropine versus cyclopentolate cycloplegia on ocular biometry in myopic children and to determine the sites of action for atropine. A total of 207 myopic children aged 6-12-years were included in the analysis. All participants underwent comprehensive eye examinations before and after cyclopentolate cycloplegia, after which they were randomly assigned into two groups, A and B, in a ratio of 1:1, to receive 1% or 0.01% atropine, respectively. The treatment was administered once every night for a week. Participants were re-examined one week later. Cyclopentolate cycloplegia caused a decrease in choroidal thickness (-3 ± 9 μm, p = 0.001), elongation of axial length (9 ± 16 μm, p < 0.001), loss of lens power (-0.14 ± 0.37 dioptre, p < 0.001), and a hyperopic shift (0.14 ± 0.22 dioptre, p < 0.001) in both groups. However, ocular biometry showed different changes after one-week use of 1% or 0.01% atropine (all p < 0.001). In Group A, choroid thickening (24 ± 13 μm, p < 0.001) and reduced axial length (-30 ± 27 μm, p < 0.001) were observed after atropine cycloplegia, with greater changes in lens power (0.50 ± 0.37 dioptre, p < 0.001) and spherical equivalent (0.52 ± 0.23 dioptre, p < 0.001). Group B showed a slight increase in choroidal thickness following one-week use of 0.01% atropine (6 ± 9 μm, p < 0.001), but other biometric measures showed no significant changes. Cyclopentolate and atropine cycloplegia have different effects on ocular biometry. Both 1% cyclopentolate cycloplegia and 0.01% atropine resulted in choroidal thickening, indicating that the choroid may be a site of action for atropine.


Linking void and interphase evolution to electrochemistry in solid-state batteries using operando X-ray tomography.
Despite progress in solid-state battery engineering, our understanding of the chemo-mechanical phenomena that govern electrochemical behaviour and stability at solid-solid interfaces remains limited compared to at solid-liquid interfaces. Here, we use operando synchrotron X-ray computed microtomography to investigate the evolution of lithium/solid-state electrolyte interfaces during battery cycling, revealing how the complex interplay among void formation, interphase growth and volumetric changes determines cell behaviour. Void formation during lithium stripping is directly visualized in symmetric cells, and the loss of contact that drives current constriction at the interface between lithium and the solid-state electrolyte (Li10SnP2S12) is quantified and found to be the primary cause of cell failure. The interphase is found to be redox-active upon charge, and global volume changes occur owing to partial molar volume mismatches at either electrode. These results provide insight into how chemo-mechanical phenomena can affect cell performance, thus facilitating the development of solid-state batteries.


Infrared Thermography to Evaluate Heat Tolerance in Different Genetic Groups of Lambs.
Heat stress is considered a limiting factor for sheep production. We used information from physiological characteristics linked to heat tolerance to determine whether infrared thermography temperatures were able to separate groups of animals and determine the most important variables in this differentiation. Forty-eight four-month-old male lambs from eight genetic groups were used. Physiological (rectal temperature-RT, heart rate-HR, respiratory rate-RR) and blood traits, infrared thermography temperatures, heat tolerance indices, body measurements, weight and carcass traits were measured. Statistical analyses included variance, correlations, factor, discrimination and regression. Observing the correlations between physiological characteristics (RT, RR and HR) with temperatures measured by infrared thermography, regions for further studies should include the mean temperature of flank, nose and rump. Results show that there are strong relationships between thermograph measurements and RR, RT and HR in lambs, which are suggested to be directly correlated with heat tolerance capacity of the different genetic groups evaluated in this study. The assessment of body surface temperature measured by the thermograph could be used as a noninvasive tool to assess heat tolerance of the animals.


Stavudine plus didanosine and nevirapine in antiretroviral-naive HIV-infected adults: preliminary safety and efficacy results. VIRGO Study Team.
The objective of this open-label trial is to evaluate the virological and immunological effects of triple therapy with stavudine (40 mg twice daily if > or = 60 kg, 30 mg twice daily if < 60 kg)/didanosine (400 mg once daily if > or = 60 kg, 300 mg once daily if < 60 kg)/nevirapine (200 mg daily from day 1 to 14, then 200 mg twice daily) in 60 antiretroviral-naive HIV-infected adults with CD4 cell counts > or = 200 cells/mm3 and plasma HIV RNA > or = 5000 copies/ml. At present, 59 patients have begun receiving the trial regimen. Characteristics of patients at baseline were as follows: 46 men/13 women, CDC stage A, 75%; mean CD4 cell count, 429 cells/mm3; mean HIV RNA, 4.6 log10 copies/ml). Mean decrease of viral load was -1.9 log10 at week 4 (n = 39), -1.9 log10 at week 16 (n = 20), with HIV RNA below the detectable level (< 500 copies/ml) in 62% of patients at week 4 and 85% at week 16. Mean CD4 cell count increase was +118 cells/mm3 at week 4. Cutaneous intolerance occurred within the first 4 weeks in 11/59 (19%) patients after a mean of 14 days (range, 3-24 days) and led to nevirapine discontinuation in 3/11 patients. Preliminary results of this ongoing trial show that combination therapy with stavudine/didanosine/nevirapine is a convenient (seven pills in two daily intakes) triple-therapy regimen with rapid immunological and antiviral effects. Rash, frequent in the first weeks of therapy, usually can be managed without stopping nevirapine. Long-term suppression of plasma HIV RNA with this combination needs to be confirmed but may support use of nevirapine as a component of first-line anti-HIV therapy along with two nucleosides.


Bupleurum polysaccharides attenuates lipopolysaccharide-induced inflammation via modulating Toll-like receptor 4 signaling.
Bupleurum polysaccharides (BPs), isolated from Bupleurum smithii var. parvifolium, possesses immunomodulatory activity, particularly on inflammation. Bacterial endotoxin lipopolysaccharide (LPS) triggers innate immune responses through Toll-like receptor 4 (TLR4) on host cell membrane. The present study was performed to evaluate whether the therapeutic efficacy of BPs on suppression of LPS's pathogenecity could be associated with the modulating of TLR4 signaling pathway. LPS stimulated expression and activation of factors in the TLR4 signaling system, including TLR4, CD14, IRAK4, TRAF6, NF-κB, and JNK, determined using immunocytochemical and/or Western blot assays. BPs significantly inhibited these effects of LPS. LPS increased pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-12p40, and IFN-β) and NO production, evaluated using ELISA and Griess reaction assays, respectively. BPs antagonized these effects of LPS. Interestingly, BPs alone augmented secretion of some pro-inflammatory cytokines of non-LPS stimulated macrophages and enhanced phagocytic activity towards fluorescent E.coli bioparticles. In a rat model of acute lung injury (ALI) with pulmonary hemorrhage and inflammation, BPs ameliorated lung injuries and suppressed TLR4 expression. The therapeutic properties of BPs in alleviating inflammatory diseases could be attributed to its inhibitory effect on LPS-mediated TLR4 signaling.


Oral Transmucosal Cannabidiol Oil Formulation as Part of a Multimodal Analgesic Regimen: Effects on Pain Relief and Quality of Life Improvement in Dogs Affected by Spontaneous Osteoarthritis.
The aim of this study was to evaluate the efficacy of oral transmucosal (OTM) cannabidiol (CBD), in addition to a multimodal pharmacological treatment for chronic osteoarthritis-related pain in dogs. Twenty-one dogs were randomly divided into two groups: in group CBD (n = 9), OTM CBD (2 mg kg-1 every 12 h) was included in the therapeutic protocol (anti-inflammatory drug, gabapentin, amitriptyline), while in group C (n = 12), CBD was not administered. Dogs were evaluated by owners based on the Canine Brief Pain Inventory scoring system before treatment initiation (T0), and one (T1), two (T2), four (T3) and twelve (T4) weeks thereafter. Pain Severity Score was significantly lower in CBD than in C group at T1 (p = 0.0002), T2 (p = 0.0043) and T3 (p = 0.016). Pain Interference Score was significantly lower in CBD than in C group at T1 (p = 0.0002), T2 (p = 0.0007) and T4 (p = 0.004). Quality of Life Index was significantly higher in CBD group at T1 (p = 0.003). The addition of OTM CBD showed promising results. Further pharmacokinetics and long-term studies in larger populations are needed to encourage its inclusion into a multimodal pharmacological approach for canine osteoarthritis-related pain.