Effects of fructooligosaccharides on the absorption of magnesium in the magnesium-deficient rat model.
Magnesium (Mg) is an essential dietary element that plays important roles, acting as a cofactor of many enzymes. Rats fed a Mg-deficient diet have been reported to exhibit auricular and facial peripheral hyperemia and hemorrhage. Moreover, increased intake of calcium (Ca) or phosphorus (P) has been reported to impair apparent absorption of Mg. We tried to induce such typical inflammation in Mg-deficient rats by feeding low-Mg, high-Ca, and high-P diets. Increasing concentrations of Ca or P in the experimental diets significantly decreased the apparent absorption of Mg. And all rats fed the low-Mg (0.25 mg/g diet), high-Ca (10.4 mg/g diet), and high-P (12.0 mg/g diet) diet exhibited auricular and facial peripheral-hyperemia and hemorrhage. Then, we used the low-Mg, high-Ca, and high-P diet to investigate the effects of the fructooligosaccharides (FO) on absorption of Mg and skin inflammation. In the rats fed FO-containing (1 or 5%) diet, apparent absorption of Mg was significantly increased as compared with that of the control (FO 0%) group. In the rats fed a 5% FO-containing diet and sufficient Mg (0.50 mg/g), auricular and facial peripheral hyperemia and hemorrhage were significantly reduced. We concluded that FO increased the Mg absorption in rats fed a low-Mg, high-Ca, and high-P diet. Moreover, FO reduced inflammation in Mg-deficient rats, such as peripheral hyperemia and hemorrhage.


Supratentorial acute subdural haematoma during microvascular decompression surgery: report of three cases.
Supratentoiral haemorrhage during posterior fossa surgery is very rare. Authors report three cases of acute subdural haematoma occurred during microvascular decompression (MVD). Bleeding was observed in the suboccipital surgical area during operation but the origin of the bleeding was not confirmed intraoperatively in all cases. Decompression procedure was completed and immediate postoperative computed tomography revealed supratentorial subdural haematoma. This complication was observed during MVD in healthy young patients with hemifacial spasm in our cases. Flexion of the head with reduction of cerebrospinal fluid may have induced rotational movement of the cerebrum resulting in rupture of bridging veins, but no definitive mechanism that fulfils the clinical characteristics was clearly determined.


New insights into the reaction of zinc alkyls with dioxygen.
Studies on the reaction of zinc alkyls with O2 are reported which demonstrate that the selective oxygenation of organozinc compound is viable. The reaction of [EtZn(azol)]n (azol = deprotonated 1-aziridineethanol) with an excess of dry O2 in toluene affords the zinc ethylperoxide [EtOOZn(azol)]2[EtZn(azol)]2, while the analogous reaction between Me2Zn and O2 results in the isolation of the Me6Zn7(OMe)8 cluster in high yield.


Comprehensive chromosome screening and gene expression analysis from the same biopsy in human preimplantation embryos.
Can simultaneous comprehensive chromosome screening (CCS) and gene expression analysis be performed on the same biopsy of preimplantation human embryos? For the first time, CCS and reliable gene expression analysis have been performed on the same human preimplantation embryo biopsy. A single trophectoderm (TE) biopsy is routinely used for many IVF programs offering CCS for selection of only chromosomally normal embryos for transfer. Although the gene expression profiling of human preimplantation embryos has been described, to date no protocol allows for simultaneous CCS and gene expression profiling from a single TE biopsy. This is a proof of concept and validation study structured in two phases. In Phase 1, cell lines were subjected to a novel protocol for combined CCS and gene expression analysis so as to validate the accuracy and reliability of the proposed protocol. In Phase 2, 20 donated human blastocysts were biopsied and processed with the proposed protocol in order to obtain an accurate CCS result and characterize their gene expression profiles using the same starting material. A novel protocol coupling quantitative real-time PCR-based CCS and gene expression analysis using RT-PCR was designed for this study. Phase 1: six-cell aliquots of well-characterized fibroblast cell lines (GM00323, 46,XY and GM04435, 48,XY,+16,+21) were subjected to the proposed protocol. CCS results were compared with the known karyotypes for consistency, and gene expression levels were compared with levels of purified RNA from same cell lines for validation of reliable gene expression profiling. Phase 2: four biopsies were performed on 20 frozen human blastocysts previously diagnosed as trisomy 21 (10 embryos) and monosomy 21 (10 embryos) by CCS. All samples were processed with the proposed protocol and re-evaluated for concordance with the original CCS result. Their gene expression profiles were characterized and differential gene expression among embryos and early embryonic cell lineages was also evaluated. CCS results from cell lines showed 100% consistency with their known karyotypes. ΔΔCt values of differential gene expression of four selected target genes from the cell lines GM4435 and GM0323 were comparable between six-cell aliquots and purified RNA (Collagen type I alpha-1 (COL1A1), P = 0.54; Fibroblast growth factor-5 (FGF5), P = 0.11; Laminin subunit beta-1 (LAMB1), P = 1.00 and Atlastin-1 (ATL1), P = 0.23). With respect to human blastocysts, 92% consistency was reported after comparing embryonic CCS results with previous diagnosis. A total of 30 genes from a human stem cell pluripotency panel were selected to evaluate gene expression in human embryos. Correlation coefficients of expression profiles from biopsies of the same embryo (r = 0.96 ± 0.03 (standard deviation), n = 45) were significantly higher than when biopsies from unrelated embryos were evaluated (r = 0.93 ± 0.03, n = 945) (P < 0.0001). Growth differentiation factor 3 (GDF3) was found to be significantly up-regulated in the inner cell mass (ICM), whereas Caudal type homebox protein-2 (CDX2), Laminin subunit alpha-1 (LAMA1) and DNA methyltransferase 3-beta (DNMT3B) showed down-regulation in ICM compared with TE. Trisomy 21 embryos showed significant up-regulation of markers of cell differentiation (Cadherin-5 (CDH5) and Laminin subunit gamma-1 (LAMC1)), whereas monosomy 21 blastocysts showed higher expression of genes reported to be expressed in undifferentiated cells (Gamma-Aminobutyric Acid Type-A Receptor Beta3 Subunit (GABRB3) and GDF3). N/A. Gene expression profiles of chromosomally normal embryos were not assessed due to restrictive access to euploid embryos for research. Nonetheless, the profile of blastocysts with single aneuploidies was characterized and compared. Only 30 target genes were analyzed for gene expression in this study. Increasing the number of target genes will provide a more comprehensive transcriptomic signature and reveal potential pathways paramount for embryonic competence and correct development. This is the first time that CCS and gene expression analysis have been performed on the same human preimplantation embryo biopsy. Further optimization of this protocol with other CCS platforms and inclusion of more target genes will provide innumerable research and clinical applications, such as discovery of biomarkers for embryonic reproductive potential and characterization of the transcriptomic signatures of embryos, potentially allowing for further embryo selection prior to embryo transfer and therefore improving outcomes. This study was funded by the Foundation for Embryonic Competence, Basking Ridge, NJ, USA. No conflicts of interests declared.


Magnetic microsphere confined ionic liquid as a novel sorbent for the determination of chlorophenols in environmental water samples by liquid chromatography.
Magnetic microsphere confined ionic liquid was synthesized by covalently bonding N-methylimidazolium on magnetic microspheres. The functionalized magnetic microspheres were characterized by Fourier transform infrared (FT-IR) spectrometry, thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The prepared material was used for the preconcentration of three chlorophenols (CPs) in water combined with high-performance liquid chromatography (HPLC). Several conditions that probably affected the extraction efficiency such as standing time, eluent and its volume, sample pH and volume, were optimized. Under the optimal conditions, good recoveries (70.3-88.8%) were achieved with satisfactory relative standard deviations (RSDs) of less than 6.0%. The limits of detection for the three CPs were 0.20-0.35 μg L(-1). The results indicated that the ionic liquid-functionalized magnetic microspheres show significant promise for the analysis of CPs in environmental samples.


Replication Protein A1 is essential for DNA damage repair during mammalian oogenesis.
Persistence of unrepaired DNA damage in oocytes is detrimental and may cause genetic aberrations, miscarriage, and infertility. RPA, an ssDNA-binding complex, is essential for various DNA-related processes. Here we report that RPA plays a novel role in DNA damage repair during postnatal oocyte development after meiotic recombination. To investigate the role of RPA during oogenesis, we inactivated RPA1 (replication protein A1), the largest subunit of the heterotrimeric RPA complex, specifically in oocytes using two germline-specific Cre drivers (Ddx4-Cre and Zp3-Cre). We find that depletion of RPA1 leads to the disassembly of the RPA complex, as evidenced by the absence of RPA2 and RPA3 in RPA1-deficient oocytes. Strikingly, severe DNA damage occurs in RPA1-deficient GV-stage oocytes. Loss of RPA in oocytes triggered the canonical DNA damage response mechanisms and pathways, such as activation of ATM, ATR, DNA-PK, and p53. In addition, the RPA deficiency causes chromosome misalignment at metaphase I and metaphase II stages of oocytes, which is consistent with altered transcript levels of genes involved in cytoskeleton organization in RPA1-deficient oocytes. Absence of the RPA complex in oocytes severely impairs folliculogenesis and leads to a significant reduction in oocyte number and female infertility. Our results demonstrate that RPA plays an unexpected role in DNA damage repair during mammalian folliculogenesis.


[Diagnostic procedures in pediatric hypoglycemias].
Depending on its etiology hypoglycemia appears after short or prolonged periods of fasting and shows different metabolite and hormonal patterns. In children it is caused by a disturbed homoeostasis of blood glucose (hormonal disorders, decreased activity of glycogenolysis or gluconeogenesis), by a primarily decreased ketogenic activity, or by a deranged adjustment of ketogenesis and carbohydrate metabolism. For the diagnostic procedure the age at manifestation, periods of fasting as well as signs and symptoms (f.e. hepatomegaly, growth retardation, somnolence) have to be carefully evaluated. Based on the extent of ketonemia the hypoglycemic syndromes can be classified into ketotic and hypoketotic forms. Hyperinsulinism, defects in fatty acid oxydation, glycogen storage disease I and postprandial hypoglycemias belong to the second category. In diagnosing hypoglycemia analysis of metabolite (glucose, lactate, beta-hydroxybutyrate, free fatty acids, carnitine) and hormonal (insulin, cortisol, growth hormone) patterns during hypoglycemic episodes is of outstanding importance. Urine has to be analysed for abnormal organic acids in order to demonstrate disturbed fatty acid oxydation. Rarely, loading tests with intermediates of carbohydrate metabolism are necessary. Suspected enzyme deficiencies have to be demonstrated in appropriate tissues (liver biopsy, erythrocytes, fibroblasts).


[Microbiological contamination in the dental office and its possible decrease].
A microbiological analysis of the environment after dental work is presented in this paper. Detection of oral streptococci in the air is used as an index of the presence of salivary aerosol in consequence of the use of dental tools at high spin. This salivary aerosol may be considered a very important cause for the transmission of infectious diseases in the dental surgery. The real efficacy of a tool for the production of a dry aerosol of phenols or clorexidine with the purpose of environmental disinfection, is evaluated. Among possible parameters has been considered both the spray ability of the tool and the bactericidal activity of the aerosol at variable length from the source. Data here presented demonstrate the real utility of such an instrument for the disinfection of the dental surgery to be applied daily at the end of the work, not only in reducing environment microbial counts but also in totally eliminating salivary microorganisms.


Altitude and forest edges influence the density and distribution of pygmy tarsiers (Tarsius pumilus).
In this study, we examine how high-altitude ecology and anthropogenic edges relate to the density and distribution of pygmy tarsiers. Pygmy tarsiers (Tarsius pumilus) are extremely small-bodied primates (55 g) that are endemic to high-altitude forest and exhibit several differences from lowland Sulawesian tarsier species. From June to September 2010 and January to March 2012, we conducted a population census of pygmy tarsiers across multiple altitudes. Sampling took place within a 1.2 km(2) area encompassing altitudes of 2,000-2,300 m a.s.l. on Mt. Rore Katimbu in Lore Lindu National Park, central Sulawesi, Indonesia. We observed 22 individuals, with an estimated population density of 92 individuals per 100 ha. These results indicate that pygmy tarsiers live at a lower density than lowland Sulawesian tarsier species. Lower density was associated with decreased resources at higher altitudes, including decreased tree size, tree density, and insect biomass. Within the sample area, we found pygmy tarsiers in only 8 of 24 (33%) quadrats, suggesting a nonrandom distribution that probably overinflated this population density estimate. Pygmy tarsiers exhibited a clumped distribution near anthropogenic edges that were associated with increased insect abundance and biomass. Airborne insects were more abundant along forest edges than within the forest interior, and pygmy tarsiers were observed to forage along edges where there was a higher abundance of Lepidoptera and Orthoptera. Tarsiers may mitigate the decreased availability of insects at high altitudes by adjusting their ranging patterns to remain near forest edges.


Thyroid hormone and the TRH stimulation test in refractory depression.
Seven of 21 refractory depressed patients responded within 7 days to combined thyroid hormone-antidepressant treatment. Five of the 7 responders revealed evidence of subclinical hypothyroidism, suggesting that this subpopulation of depressed patients may benefit most from adjunctive thyroid hormone.


Copper- and iron-rich matrices in hepatocellular lipofuscin particles of a young male patient: diagnostic ultrastructures for Wilson disease.
A 17-year-old male patient appeared with the biochemical liver damage associated with hypoceruloplasminemia and mild iron overload. Genetic analysis identified a compound heterozygosity of ATP7B responsible for the primary copper toxicosis of Wilson disease without mutations in HFE. A liver specimen consisted of cirrhotic nodules of large-sized hepatocytes with fatty change and those of fat-free small-sized hepatocytes. Histochemically, iron was distributed diffusely in the small-sized hepatocytes, while copper grains appeared in a few of the hepatocytes near the fibrous bands. X-ray microanalysis on the liver tissue fixed with a 0.1% osmium tetroxide solution and embedded in epoxy resin disclosed (1) complex formation of copper with sulfur, and iron with phosphorus in the hepatocyte lipofuscin particles, (2) intraparticle localization of the cuprothionein in the less dense matrix and ferric proteins in the dense matrix, and (3) high affinity of the cuprothionein to lead staining. Considering the fact that ceruloplasmin is the major ferroxidase essential for iron efflux, iron deposits in the hypoceruloplasminemic patients with Wilson disease are not a complication, but a natural event. This study disclosed for the first time the diagnostic ultrastructures of Wilson disease, which might represent different detoxification processes to the reactive metals of copper and iron.


Laboratory evaluation of transgenic Populus davidiana×Populus bolleana expressing Cry1Ac + SCK, Cry1Ah3, and Cry9Aa3 genes against gypsy moth and fall webworm.
Transgenic poplar lines 'Shanxin' (Populus davidiana×Populus bolleana) were generated via Agrobacterium-mediated transformation. The transgenic lines carried the expression cassettes of Cry1Ac + SCK, Cry1Ah3, and Cry9Aa3, respectively. The expression levels of the exogenous insect resistance genes in the transgenic lines were determined by Q-PCR and Western blot. Leaves of the transgenic lines were used for insect feeding bioassays on first instar larvae of the gypsy moth (Lymantria dispar) and fall webworm (Hyphantria cunea). At 5 d of feeding, the mean mortalities of larvae feeding on Cry1Ac + SCK and Cry1Ah3 transgenic poplars leaves were 97% and 91%, while mortality on Cry9Aa3 transgenic lines was about 49%. All gypsy moth and fall webworm larvae were killed in 7-9 days after feeding on leaves from Cry1Ac + SCK or Cry1Ah3 transgenic poplars, while all the fall webworm larvae were killed in 11 days and about 80% of gypsy moth larvae were dead in 14 days after feeding on those from Cry9Aa3 transgenic lines. It was concluded that the transgenic lines of Cry1Ac + SCK and Cry1Ah3 were highly toxic to larvae of both insect species while lines with Cry9Aa3 had lower toxicity,and H. cunea larvae are more sensitive to the insecticidal proteins compared to L. dispar. Transgenic poplar lines toxic to L. dispar and H. cunea could be used to provide Lepidoptera pest resistance to selected strains of poplar trees.


Specific heat of the simple-cubic Ising model.
We provide an expression quantitatively describing the specific heat of the Ising model on the simple-cubic lattice in the critical region. This expression is based on finite-size scaling of numerical results obtained by means of a Monte Carlo method. It agrees satisfactorily with series expansions and with a set of experimental results. Our results include a determination of the universal amplitude ratio of the specific-heat divergences at both sides of the critical point.


The role of cytokinin in ovule development in Arabidopsis.
The life cycle of higher plants alternates between the haploid gametophyte and diploid sporophyte. The female gametophyte (FG), surrounded by the sporophyte, develops within the ovule and orients along the chalazal/micropylar axis. This polarity is important in cell specification and development for both the ovule and FG. Previously, cytokinin was shown to act in the sporophytic tissue to regulate FG development. In the highlighted study, we further showed that enriched cytokinin signaling in chalaza, the central domain of the ovule, is required for the specification of the functional megaspore, which usually occurs in the chalazal-most megaspore after meiosis. The restricted cytokinin signaling in the chalaza is achieved by localized cytokinin biosynthesis and perception. Here, we discuss the implications of this and other studies for the understanding of the role of two-component signaling in FG development and the genetic and cellular interactions between gametophytic and sporophytic cells. Further, we show that cytokinin-deficient mutants display distorted cell morphology in the inner integument and elevated mitotic activity in the maternal sporophyte. These results suggest that cytokinin negatively regulates cell proliferation in the sporophytic tissues surrounding the developing FG, consistent with previous results indicating that cytokinin deficiency causes an increase in the number of cells in the embryos and consequently an enlarged seed size.


Disruption of SUMO-specific protease 2 induces mitochondria mediated neurodegeneration.
Post-translational modification of proteins by small ubiquitin-related modifier (SUMO) is reversible and highly evolutionarily conserved from yeasts to humans. Unlike ubiquitination with a well-established role in protein degradation, sumoylation may alter protein function, activity, stability and subcellular localization. Members of SUMO-specific protease (SENP) family, capable of SUMO removal, are involved in the reversed conjugation process. Although SUMO-specific proteases are known to reverse sumoylation in many well-defined systems, their importance in mammalian development and pathogenesis remains largely elusive. In patients with neurodegenerative diseases, aberrant accumulation of SUMO-conjugated proteins has been widely described. Several aggregation-prone proteins modulated by SUMO have been implicated in neurodegeneration, but there is no evidence supporting a direct involvement of SUMO modification enzymes in human diseases. Here we show that mice with neural-specific disruption of SENP2 develop movement difficulties which ultimately results in paralysis. The disruption induces neurodegeneration where mitochondrial dynamics is dysregulated. SENP2 regulates Drp1 sumoylation and stability critical for mitochondrial morphogenesis in an isoform-specific manner. Although dispensable for development of neural cell types, this regulatory mechanism is necessary for their survival. Our findings provide a causal link of SUMO modification enzymes to apoptosis of neural cells, suggesting a new pathogenic mechanism for neurodegeneration. Exploring the protective effect of SENP2 on neuronal cell death may uncover important preventive and therapeutic strategies for neurodegenerative diseases.


Formalin fixation could interfere with the clinical assessment of the tumor-free margin in tumor surgery: magnetic resonance imaging-based study.
The tumor-free margin in bone and soft-tissue cancer is a key factor for subsequent treatment. While flattening and shrinkage of specimens after formalin fixation have been described in breast cancer, there are no data for bone and soft tissue sarcoma. Fixation could interfere with the accuracy of the assessment of the tumor-free margin. The influence of formalin fixation was assessed on forelimb specimens in a preclinical porcine model. The specimens were subjected to magnetic resonance imaging before and after formalin fixation. Weight, width and height of the specimen were measured and different consecutive volumes (total, muscles, bones and fatty tissue) were obtained by segmentation. After formalin fixation, the weight increased, total volume and muscle volume slightly increased while bone did not change and fatty tissue decreased. The width of the specimens increased while their height decreased. Formalin fixation caused slight muscle expansion, fatty tissue shrinkage and flattening of the specimen. These changes could interfere with the assessment of the tumor-free margin in clinical practice.


Anisomycin inhibition of estradiol-induced and progesterone-facilitated luteinizing hormone surges in the immature rat.
These studies were designed to examine the effect of anisomycin, a potent and reversible inhibitor of protein synthesis with low systemic toxicity in rodents, on induction of luteinizing hormone (LH) surges by estradiol and their facilitation by progesterone. Immature female rats that received estradiol implants at 0900 h on Day 28 had LH surges approximately 32 h later (1700 h on Day 29). Insertion of progesterone capsules 24 h after estradiol led to premature (by 1400 h) and enhanced LH secretion. Protein synthesis was inhibited by 97%, 95%, 47%, and 16% in the hypothalamus-preoptic area (HPOA) and by 98%, 87%, 35%, and 0% in the pituitary at 30 min, 2 h, 4 h, and 6 h after s.c. injection of anisomycin (10 mg/kg BW), respectively. A single injection of anisomycin at 0, 3, 6, 9, 12, 24, 27, or 30 h after estradiol treatment significantly lowered serum LH levels at 32 h. The effect of injecting anisomycin at 0, 24, or 27 h was overridden by progesterone treatment at 24 h, but LH secretion was delayed serum LH levels were basal (10-30 ng/ml) at 1400 h but elevated (500-800 ng/ml) at 1700 h. Complete suppression of LH surges in estradiol-plus-progesterone-treated rats was achieved with 2 injections of anisomycin on Day 29 at 0900 h and again at 1200 h or 1400 h. Further experiments were designed to examine proteins that might be involved in anisomycin blockade of progesterone-facilitated LH surges. Intrapituitary LH concentrations at 1700 h on Day 29 were 70-80% higher (102 +/- 12.5 micrograms/pituitary) in rats that received 2 injections of anisomycin than in vehicle-treated controls (58.5 +/- 7.7 micrograms/pituitary). There were no significant effects of anisomycin on cytosol progestin receptors in the HPOA (7.1 +/- 1.5 fmol/tissue, anisomycin; 7.2 +/- 0.3, vehicle) or pituitary (8.3 +/- 1.3 fmol/tissue, anisomycin; 11.7 +/- 2.9, vehicle) at this time. The concentration of pituitary gonadotropin-releasing hormone receptors (GnRH-R), however, was significantly lower after anisomycin (265 +/- 30 vs. 365 +/- 37 fmol/mg protein) treatment. These results suggest that both estradiol-induced and progesterone-facilitated LH surges involve protein synthetic steps extending over many hours. Blockade of progesterone-facilitated LH surges by anisomycin appears to be due primarily to an effect on release of LH to which lowering of GnRH-R levels may contribute.


Drug-induced lung disease: high-resolution CT and histological findings.
To compare the parenchymal high-resolution computed tomography (HRCT) appearances with histological findings in patients with drug-induced lung disease and to determine the prognostic value of HRCT. Drug history, HRCT features, histological findings and outcome at 3 months in 20 patients with drug induced-lung disease were reviewed retrospectively. The HRCT images were assessed for the pattern and distribution of abnormalities and classified as most suggestive of interstitial pneumonitis/fibrosis, diffuse alveolar damage (DAD), organizing pneumonia (OP) reaction, or a hypersensitivity reaction. On histopathological examination there were eight cases of interstitial pneumonitis/fibrosis, five of DAD, five of OP reactions, one of hypersensitivity reaction and one of pulmonary eosinophilia. The most common abnormalities on HRCT were ground-glass opacities (n = 17), consolidation (n = 14), interlobular septal thickening (n = 15) and centrilobular nodules (n = 8). HRCT interpretation and histological diagnosis were concordant in only nine (45%) of 20 patients. The pattern, distribution, and extent of HRCT abnormalities were of limited prognostic value: all eight patients with histological findings of OP, hypersensitivity reaction, or eosinophilic infiltrate improved on follow-up compared to only five of 13 patients with interstitial pneumonitis/fibrosis or DAD. In many cases of drug-induced lung injury HRCT is of limited value in determining the histological pattern and prognosis.


Rapid Analysis of Bisphenol A and Its Analogues in Food Packaging Products by Paper Spray Ionization Mass Spectrometry.
In this study, a paper spray ionization mass spectrometric (PS-MS) method was developed for the rapid in situ screening and simultaneous quantitative analysis of bisphenol A and its analogues, i.e., bisphenol S, bisphenol F, and bisphenol AF, in food packaging products. At the optimal PS-MS conditions, the calibration curves of bisphenols in the range of 1-100 μg/mL were linear. The correlation coefficients were higher than 0.998, and the LODs of the target compounds were 0.1-0.3 μg/mL. After a simple treatment by dichloromethane on the surface, the samples were analyzed by PS-MS in situ for rapid screening without a traditional sample pretreatment procedure, such as powdering, extraction, and enrichment steps. The analytical time of the PS-MS method was less than 1 min. In comparison with conventional HPLC-MS/MS, it was demonstrated that PS-MS was a more effective high-throughput screening and quantitative analysis method.


Erythropoietin administration during primary treatment for locally advanced cervical carcinoma is associated with poor response to radiation.
The purpose of this study was to determine whether the use of recombinant erythropoietin (r-EPO) during treatment for locally invasive carcinoma of the cervix affects recurrence rates, disease-free survival, and overall survival. Retrospective analysis of outcomes of patients with locally advanced cervical cancer treated with radiation and concurrent chemotherapy between January 1997 and July 2004 was performed. Recurrence rates, disease-free survival, and overall survival were calculated using SPSS statistical software. Throughout P < 0.05 was considered significant. Of 68 patients included in this study, 18 patients received erythropoietin during treatment and 50 did not. Patient age, stage, hemoglobin at presentation, and average weekly hemoglobin (AWH) were similar in both groups of patients. The recurrence rate among patients who received r-EPO was 61% compared with 30% among patients who did not receive r-EPO (P = 0.014). Eight of 18 patients (44%) who received r-EPO were alive at last known follow-up compared to 36 of 50 (72%) who did not receive the medication (P = 0.045). Disease-free survival and overall survival were significantly shorter in patients who received r-EPO during treatment (P = 0.028, 0.032). The administration of r-EPO during primary treatment of patients with locally advanced cervical cancer is associated with increased recurrence rate, increased risk of death due to disease, and decreased disease-free and overall survivals.


Transcription Factor GmWRKY142 Confers Cadmium Resistance by Up-Regulating the Cadmium Tolerance 1-Like Genes.
Cadmium (Cd) is a widespread pollutant that is toxic to living organisms. Previous studies have identified certain WRKY transcription factors, which confer Cd tolerance in different plant species. In the present study, we have identified 29 Cd-responsive WRKY genes in Soybean [Glycine max (L.) Merr.], and confirmed that 26 of those GmWRKY genes were up-regulated, while 3 were down-regulated. We have also cloned the novel, positively regulated GmWRKY142 gene from soybean and investigated its regulatory mechanism in Cd tolerance. GmWRKY142 was highly expressed in the root, drastically up-regulated by Cd, localized in the nucleus, and displayed transcriptional activity. The overexpression of GmWRKY142 in Arabidopsis thaliana and soybean hairy roots significantly enhanced Cd tolerance and lead to extensive transcriptional reprogramming of stress-responsive genes. ATCDT1, GmCDT1-1, and GmCDT1-2 encoding cadmium tolerance 1 were induced in overexpression lines. Further analysis showed that GmWRKY142 activated the transcription of ATCDT1, GmCDT1-1, and GmCDT1-2 by directly binding to the W-box element in their promoters. In addition, the functions of GmCDT1-1 and GmCDT1-2, responsible for decreasing Cd uptake, were validated by heterologous expression in A. thaliana. Our combined results have determined GmWRKYs to be newly discovered participants in response to Cd stress, and have confirmed that GmWRKY142 directly targets ATCDT1, GmCDT1-1, and GmCDT1-2 to decrease Cd uptake and positively regulate Cd tolerance. The GmWRKY142-GmCDT1-1/2 cascade module provides a potential strategy to lower Cd accumulation in soybean.


Mechanism of Charge Transfer from Plasmonic Nanostructures to Chemically Attached Materials.
Plasmonic metal nanoparticles can efficiently convert the energy of visible photons into the energy of hot charge carriers within the nanoparticles. These energetic charge carriers can transfer to molecules or semiconductors, chemically attached to the nanoparticles, where they can induce photochemical transformations. Classical models of photoinduced charge excitation and transfer in metals suggest that the majority of the energetic charge carriers rapidly decay within the metal nanostructure before they are transferred into the neighboring molecule or semiconductor, and therefore, the efficiency of charge transfer is low. Herein, we present experimental evidence that calls into question this conventional picture. We demonstrate a system where the presence of a molecule, adsorbed on the surface of a plasmonic nanoparticle, significantly changes the flow of charge within the excited plasmonic system. The nanoparticle-adsorbate system experiences high rates of direct, resonant flow of charge from the nanoparticle to the molecule, bypassing the conventional charge excitation and thermalization process taking place in the nanoparticle. This picture of charge transfer suggests that the yield of extracted hot electrons (or holes) from plasmonic nanoparticles can be significantly higher than the yields expected based on conventional models. We discuss a conceptual physical framework that allows us to explain our experimental observations. This analysis points us in a direction toward molecular control of the charge transfer process using interface and local field engineering strategies.


Psychometric properties and reference values for the ImPACT neurocognitive test battery in a sample of elite youth ice hockey players.
This cross-sectional study aimed to determine psychometric properties and reference values for ImPACT in a sample of 704 elite ice hockey players aged 13-17. Baseline ImPACT tests were completed at the beginning of the 2011-2012 season. Players aged 16-17 had better visual motor processing speed, adjusted R(2) = .0522, F(2, 45) = 10.79, β = 2.87, p < .001, and impulse control, adjusted R = .0185, F(2,45) = 7.46, β = -1.35, p = .001, than younger players, and girls had greater total symptom ratings than boys (z = -3.47, p = .0005). There were no other sex- or age-related differences in neurocognitive performance, and no effect of previous concussion on ImPACT scores. Reference values with cut-off scores are presented.


Review Insights on Salivary Proteomics Biomarkers in Oral Cancer Detection and Diagnosis.
Early detection is crucial for the treatment and prognosis of oral cancer, a potentially lethal condition. Tumor markers are abnormal biological byproducts produced by malignant cells that may be found and analyzed in a variety of bodily fluids, including saliva. Early detection and appropriate treatment can increase cure rates to 80-90% and considerably improve quality of life by reducing the need for costly, incapacitating medicines. Salivary diagnostics has drawn the interest of many researchers and has been proven to be an effective tool for both medication monitoring and the diagnosis of several systemic diseases. Since researchers are now searching for biomarkers in saliva, an accessible bodily fluid, for noninvasive diagnosis of oral cancer, measuring tumor markers in saliva is an interesting alternative to blood testing for early identification, post-treatment monitoring, and monitoring high-risk lesions. New molecular markers for oral cancer detection, treatment, and prognosis have been found as a result of developments in the fields of molecular biology and salivary proteomics. The numerous salivary tumor biomarkers and how they relate to oral cancer and pre-cancer are covered in this article. We are optimistic that salivary protein biomarkers may one day be discovered for the clinical detection of oral cancer because of the rapid advancement of proteomic technology.


Nerve Stimulator versus Ultrasound-Guided Femoral Nerve Block; a Randomized Clinical Trial.
Pain control is the most important issue in emergency department management of patients with femoral bone fractures. The present study aimed to compare the procedural features of ultrasonography and nerve stimulator guided femoral nerve block in this regard. In this randomized clinical trial, patients with proximal femoral fractures presenting to emergency department were randomly divided into two groups of ultrasonography or nerve stimulator guided femoral block and compared regarding success rate, procedural time, block time, and need for rescue doses of morphine sulfate, using SPSS 20. 50 patients were randomly divided into two groups of 25 (60% male). The mean age of studied patients was 35.14 ± 12.95 years (19 - 69). The two groups were similar regarding age (p= 0.788), sex (p = 0.564), and initial pain severity (p = 0.513). In 2 cases of nerve stimulator guided block, loss of pinprick sensation did not happen within 30 minutes of injection (success rate: 92%; p = 0.490). Ultrasonography guided nerve block cases had significantly lower procedural time (8.06 ± 1.92 vs 13.60 ± 4.56 minutes; p < 0.001) and lower need for rescue doses of opioid (2.68 ± 0.74 vs 5.28 ± 1.88 minutes; p < 0.001). Ultrasonography and nerve stimulator guided femoral block had the same success rate and block duration. However, the ultrasonography guided group had lower procedure time and lower need for rescue doses of morphine sulfate. Therefore, ultrasonography guided femoral block could be considered as an available, safe, rapid, and efficient method for pain management of femoral fracture in emergency department.


Screening for SARS-CoV-2 Infection Within a Psychiatric Hospital and Considerations for Limiting Transmission Within Residential Psychiatric Facilities - Wyoming, 2020.
In the United States, approximately 180,000 patients receive mental health services each day at approximately 4,000 inpatient and residential psychiatric facilities (1). SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), can spread rapidly within congregate residential settings (2-4), including psychiatric facilities. On April 13, 2020, two patients were transferred to Wyoming's state psychiatric hospital from a private psychiatric hospital that had confirmed COVID-19 cases among its residents and staff members (5). Although both patients were asymptomatic at the time of transfer and one had a negative test result for SARS-CoV-2 at the originating facility, they were both isolated and received testing upon arrival at the state facility. On April 16, 2020, the test results indicated that both patients had SARS-CoV-2 infection. In response, the state hospital implemented expanded COVID-19 infection prevention and control (IPC) procedures (e.g., enhanced screening, testing, and management of new patient admissions) and adapted some standard IPC measures to facilitate implementation within the psychiatric patient population (e.g., use of modified face coverings). To assess the likely effectiveness of these procedures and determine SARS-CoV-2 infection prevalence among patients and health care personnel (HCP) (6) at the state hospital, a point prevalence survey was conducted. On May 1, 2020, 18 days after the patients' arrival, 46 (61%) of 76 patients and 171 (61%) of 282 HCP had nasopharyngeal swabs collected and tested for SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction. All patients and HCP who received testing had negative test results, suggesting that the hospital's expanded IPC strategies might have been effective in preventing the introduction and spread of SARS-CoV-2 infection within the facility. In congregate residential settings, prompt identification of COVID-19 cases and application of strong IPC procedures are critical to ensuring the protection of other patients and staff members. Although standard guidance exists for other congregate facilities (7) and for HCP in general (8), modifications and nonstandard solutions might be needed to account for the specific needs of psychiatric facilities, their patients, and staff members.


Carbon monoxide exposure from aircraft fueling vehicles.
Investigators from the National Institute for Occupational Safety and Health observed deficiencies in maintenance of fueling trucks at an international airport. The exhaust system is vented under the front bumper, a standard design on fueling trucks which is intended to minimize the proximity of the exhaust system to the jet fuel in the vehicles. Carbon monoxide levels were measured in the cabs of 17 fueling trucks with windows closed, heaters on, and in different positions relative to the wind. One truck had an average CO level of 300 ppm, two exceeded 100 ppm, five others exceeded 50 ppm, while levels in the other nine averaged less than or equal to 500 ppm. Levels of CO depended on the mechanical condition of the vehicle and the vehicle's orientation to the wind. Stringent maintenance is required as the exhaust design is not fail-safe.


The anti-sepsis activity of the components of Huanglian Jiedu Decoction with high lipid A-binding affinity.
Huanglian Jiedu Decoction (HJD), one of the classic recipes for relieving toxicity and fever, is a common method for treating sepsis in China. However, the effective components of HJD have not yet been identified. This experiment was carried out to elucidate the effective components of HJD against sepsis. Thus, seven fractions from HJD were tested using a biosensor to test their affinity for lipid A. The components obtained that had high lipid A-binding fractions were further separated, and their affinities to lipid A were assessed with the aid of a biosensor. The levels of LPS in the blood were measured, and pathology experiments were conducted. The LPS levels and mRNA expression analysis of TNF-α and IL-6 of the cell supernatant and animal tissue were evaluated to investigate the molecular mechanisms. Palmatine showed the highest affinity to lipid A and was evaluated by in vitro and in vivo experiments. The results of the in vitro and in vivo experiments indicated that the levels of LPS, TNF-α and IL-6 of the palmatine group were significantly lower than those of the sepsis model group (p<0.01). The group treated with palmatine showed strong neutralizing LPS activity in vivo. The palmatine group exhibited stronger protective activity on vital organs compared to the LPS-induced animal model. This verifies that HJD is a viable treatment option for sepsis given that there are multiple components in HJD that neutralize LPS, decrease the release of IL-6 and TNF-α induced by LPS, and protect vital organs.


Dietary Anthocyanins and Stroke: A Review of Pharmacokinetic and Pharmacodynamic Studies.
Cerebrovascular accidents are currently the second major cause of death and the third leading cause of disability in the world, according to the World Health Organization (WHO), which has provided protocols for stroke prevention. Although there is a multitude of studies on the health benefits associated with anthocyanin (ACN) consumption, there is no a rigorous systematization of the data linking dietary ACN with stroke prevention. This review is intended to present data from epidemiological, in vitro, in vivo, and clinical studies dealing with the stroke related to ACN-rich diets or ACN supplements, along with possible mechanisms of action revealed by pharmacokinetic studies, including ACN passage through the blood-brain barrier (BBB).


Differential regulation of interleukin-6 and inducible cyclooxygenase gene expression by cytokines through prostaglandin-dependent and -independent mechanisms in human dental pulp fibroblasts.
Increased levels of interleukin-1 (IL)-1, tumor necrosis factor-alpha (TNF-alpha), IL-6, and prostaglandin E2 (PGE2) have been detected in inflamed pulp tissue. To gain further insight into the molecular pathogenesis of pulpitis, we investigated the effects of IL-1alpha or TNF-alpha and PGE2, either alone or in combination on IL-6 and cyclooxygenase (COX)-2 messenger RNA (mRNA) production in cultured human dental pulp (HDP) fibroblasts. Exposure of HDP fibroblasts to IL-1alpha or TNF-alpha resulted in elevated levels of IL-6 (approximately 3.4 to approximately 10.4-fold) and COX-2 (approximately 5 to approximately 6.2-fold) mRNA. Simultaneous addition of IL-1alpha and PGE2 or TNF-alpha and PGE2 to the cultures significantly reduced the cytokine-induced IL-6 mRNA synthesis ranging from 45% to 65%. However, indomethacin enhanced the cytokine-stimulated IL-6 mRNA synthesis by approximately 1.7 to approximately 3.4-fold. This action could be reversed by exogenous PGE2. In contrast, PGE2 or indomethacin failed to modify the stimulatory effect of IL-1alpha or TNF-alpha on COX-2 gene expression. Because excessive levels of IL-6 and prostaglandins have been connected with the pathogenesis of several inflammatory diseases, our results suggest the involvement of HDP fibroblasts in the development of pulpitis via producing IL-6 and COX-2. Furthermore, expression of IL-6 and COX-2 genes in this cell seems to be differentially regulated by cytokines through prostaglandin-dependent and -independent pathways.


Adenocarcinoma of the hepatic duct junction. A reappraisal of the histologic criteria of malignancy.
The morphologic distinction between benign and malignant sclerotic processes involving the hepatic duct junction may be difficult. To determine reliable histologic criteria of malignancy, the authors reviewed 18 cases of clinically suspected adenocarcinoma of the hepatic duct junction (Klatskin tumor) retrieved from our autopsy and surgical pathology files over the last decade. The lesions were compared histologically to a variety of benign sclerotic biliary duct lesions, including four cases of primary sclerosing cholangitis (PSC) treated surgically over the same time period. A diagnosis of malignancy was confirmed histologically in 16 suspected Klatskin tumors, based on the presence of severe cytologic atypia (13) and/or perineural invasion (15). The tumor patients averaged 59 years of age with a male to female ratio of 2:1. Patients with segmental tumor resection and postoperative radiotherapy have survived as a group 6 months longer (average, 15.7 months) than those treated with drainage procedures alone (average, 9.5 months) (P less than 0.005), but have had extensive postoperative morbidity. In all the surgical specimens, tumor was present at one or more margins of resection. Primary sclerosing cholangitis patients were younger (average, 31 years of age) with a similar male predominance, but with a strong history of inflammatory bowel disease. All are alive up to 6.5 years since disease onset, with comparatively little postoperative morbidity. Two clinically diagnosed Klatskin tumors were not confirmed on histologic review. Both patients are alive at 1 and 3.5 years following onset of disease, having experienced little postoperative morbidity. Data indicate that Klatskin tumors are relatively aggressive malignancies, distinct from more indolent benign sclerotic disease, but occasionally mimicked by it clinically. Malignancy can be diagnosed histologically with adequate tissue sampling, thereby facilitating clinical decisions regarding radiotherapy or other palliative surgical procedures.


Enhanced catalytic performance of a PdO catalyst prepared via a two-step method of in situ reduction-oxidation.
A supported PdO nanocatalyst prepared by a facile in situ reduction process followed by an oxidation step showed significantly enhanced activity for the removal of pollutants from natural gas vehicles. The excellent catalytic performance is mainly due to high dispersion of the uniform PdO nanoparticles generated during the novel two-step method.


Development and External Validation of Nomograms for Predicting Survival in Nasopharyngeal Carcinoma Patients after Definitive Radiotherapy.
The distant metastasis free survival (DMFS) and overall survival (OS) differ significantly among individuals even within the same clinical stages. The purpose of this retrospective study was to build nomograms incorporating plasma EBV DNA for predicting DMFS and OS of nasopharyngeal carcinoma (NPC) patients after definitive radiotherapy. A total of 1168 non-metastatic NPC patients from two institutions were included to develop the nomograms. Seven and six independent prognostic factors were identified to build the nomograms for OS and DMFS, respectively. The models were externally validated by a separate cohort of 756 NPC patients from the third institutions. For predicting OS, the c-index of the nomogram was significantly better than that of the TNM staging system (Training cohort, P = 0.005; validation cohort, P = 0.03). The c-index of nomogram for DMFS in the training and validation set were both higher than that of TNM classification with marginal significance (P = 0.048 and P = 0.057, respectively). The probability of 1-, 3-, and 5-year OS and DMFS showed optimal agreement between nomogram prediction and actual observation. The proposed stratification of risk groups based on the nomograms allowed significant distinction between Kaplan-Meier curves for survival outcomes. The prognostic nomograms could better stratify patients into different risk groups.


Evaluation of Atlas-Based Attenuation Correction for Integrated PET/MR in Human Brain: Application of a Head Atlas and Comparison to True CT-Based Attenuation Correction.
Attenuation correction (AC) for integrated PET/MR imaging in the human brain is still an open problem. In this study, we evaluated a simplified atlas-based AC (Atlas-AC) by comparing (18)F-FDG PET data corrected using either Atlas-AC or true CT data (CT-AC). We enrolled 8 patients (median age, 63 y). All patients underwent clinically indicated whole-body (18)F-FDG PET/CT for staging, restaging, or follow-up of malignant disease. All patients volunteered for an additional PET/MR of the head (additional tracer was not injected). For each patient, 2 AC maps were generated: an Atlas-AC map registered to a patient-specific liver accelerated volume acquisition-Flex MR sequence and using a vendor-provided head atlas generated from multiple CT head images and a CT-based AC map. For comparative AC, the CT-AC map generated from PET/CT was superimposed on the Atlas-AC map. PET images were reconstructed from the list-mode raw data from the PET/MR imaging scanner using each AC map. All PET images were normalized to the SPM5 PET template, and (18)F-FDG accumulation was quantified in 67 volumes of interest (VOIs; automated anatomic labeling atlas). Relative difference (%diff) between images based on Atlas-AC and CT-AC was calculated, and averaged difference images were generated. (18)F-FDG uptake in all VOIs was compared using Bland-Altman analysis. The range of error in all 536 VOIs was -3.0%-7.3%. Whole-brain (18)F-FDG uptake based on Atlas-AC was slightly underestimated (%diff = 2.19% ± 1.40%). The underestimation was most pronounced in the regions below the anterior/posterior commissure line, such as the cerebellum, temporal lobe, and central structures (%diff = 3.69% ± 1.43%, 3.25% ± 1.42%, and 3.05% ± 1.18%), suggesting that Atlas-AC tends to underestimate the attenuation values of the skull base bone. When compared with the gold-standard CT-AC, errors introduced using Atlas-AC did not exceed 8% in any brain region investigated. Underestimation of (18)F-FDG uptake was minor (<4%) but significant in regions near the skull base.


Multi-Omics Signatures Identification for LUAD Prognosis Prediction Model Based on the Integrative Analysis of Immune and Hypoxia Signals.
Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer with heterogeneous outcomes and diverse therapeutic responses. However, the understanding of the potential mechanism behind LUAD initiation and progression remains limited. Increasing evidence shows the clinical significance of the interaction between immune and hypoxia in tumor microenvironment. To mine reliable prognostic signatures related to both immune and hypoxia and provide a more comprehensive landscape of the hypoxia-immune genome map, we investigated the hypoxia-immune-related alteration at the multi-omics level (gene expression, somatic mutation, and DNA methylation). Multiple strategies including lasso regression and multivariate Cox proportional hazards regression were used to screen the signatures with clinical significance and establish an incorporated prognosis prediction model with robust discriminative power on survival status on both the training and test datasets. Finally, combing all the samples, we constructed a robust model comprising 19 signatures for the prognosis prediction of LUAD patients. The results of our study provide a comprehensive landscape of hypoxia-immune related genetic alterations and provide a robust prognosis predictor for LUAD patients.


Bacterial communities found in placental tissues are associated with severe chorioamnionitis and adverse birth outcomes.
Preterm birth is a major cause of neonatal mortality and morbidity worldwide. Bacterial infection and the subsequent inflammatory response are recognised as an important cause of preterm birth. It is hypothesised that these organisms ascend the cervical canal, colonise placental tissues, cause chorioamnionitis and in severe cases infect amniotic fluid and the foetus. However, the presence of bacteria within the intrauterine cavity does not always precede chorioamnionitis or preterm birth. Whereas previous studies observing the types of bacteria present have been limited in size and the specificity of a few predetermined organisms, in this study we characterised bacteria found in placental tissues from a cohort of 1391 women in rural Malawi using 16S ribosomal RNA gene sequencing. We found that specific bacteria found concurrently on placental tissues associate with chorioamnionitis and delivery of a smaller newborn. Severe chorioamnionitis was associated with a distinct difference in community members, a higher bacterial load and lower species richness. Furthermore, Sneathia sanguinengens and Peptostreptococcus anaerobius found in both matched participant vaginal and placental samples were associated with a lower newborn length-for-age Z-score. This is the largest study to date to examine the placental microbiome and its impact of birth outcomes. Our results provide data on the role of the vaginal microbiome as a source of placental infection as well as the possibility of therapeutic interventions against targeted organisms during pregnancy.


Anemia in cirrhosis: An underestimated entity.
Anemia in a patient with cirrhosis is a clinically pertinent but often overlooked clinical entity. Relevant guidelines highlight the algorithmic approach of managing a patient of cirrhosis presenting with acute variceal hemorrhage but day-to-day management in hospital and out-patient raises multiple dilemmas: Whether anemia is a disease complication or a part of the disease spectrum? Should iron, folic acid, and vitamin B complex supplementation and nutritional advice, suffice in those who can perform tasks of daily living but have persistently low hemoglobin. How does one investigate and manage anemia due to multifactorial etiologies in the same patient: Acute or chronic blood loss because of portal hypertension and bone marrow aplasia secondary to hepatitis B or C viremia? To add to the clinician's woes the prevalence of anemia increases with increasing disease severity. We thus aim to critically analyze the various pathophysiological mechanisms complicating anemia in a patient with cirrhosis with an emphasis on the diagnostic flowchart in such patients and proposed management protocols thereafter.


A High-throughput Compatible Assay to Evaluate Drug Efficacy against Macrophage Passaged Mycobacterium tuberculosis.
The early drug development process for anti-tuberculosis drugs is hindered by the inefficient translation of compounds with in vitro activity to effectiveness in the clinical setting. This is likely due to a lack of consideration for the physiologically relevant cellular penetration barriers that exist in the infected host. We recently established an alternative infection model that generates large macrophage aggregate structures containing densely packed M. tuberculosis (Mtb) at its core, which was suitable for drug susceptibility testing. This infection model is inexpensive, rapid, and most importantly BSL-2 compatible. Here, we describe the experimental procedures to generate Mtb/macrophage aggregate structures that would produce macrophage-passaged Mtb for drug susceptibility testing. In particular, we demonstrate how this infection system could be directly adapted to the 96-well plate format showing throughput capability for the screening of compound libraries against Mtb. Overall, this assay is a valuable addition to the currently available Mtb drug discovery toolbox due to its simplicity, cost effectiveness, and scalability.


Rapidly progressive hippocampal atrophy: evidence for a seizure-induced mechanism.
Hippocampal formation atrophy (HFA) developed in an adult, who did not have epilepsy previously, after the occurrence of new-onset partial seizures from acute thrombosis of an ipsilateral parietal venous angioma. There was no evidence of hippocampal injury, and the patient had only one brief, generalized tonic-clonic seizure. Although HFA progressed rapidly over 5.5 months, the partial seizures did not become prolonged or secondarily generalized. Evidence from the patient indicates that partial seizure activity can cause rapid and progressive hippocampal atrophy.


AP-1 complexes mediate oxidized LDL-induced overproduction of TGF-beta(1) in rat mesangial cells.
Oxidized Low Density Lipoprotein (Ox-LDL)-induced overproduction of the prosclerotic cytokine transforming growth factor-beta1 (TGF-beta(1)) has been implicated in the pathogenesis of renal fibrosis and sclerosis. Because Ox-LDL increases TGF-beta(1) mRNA levels in rat mesangial cells, our investigation was designed to characterize these effects on the rat TGF-beta(1) promoter activity. We transfected luciferase reporter gene constructs containing TGF-beta(1) 5'-flanking sequence (from -1550 to +57 bp) into mesangial cells. By assaying progressively deleted mutations in the promoter, we found two regions that were responsible for the induction. One is a negative regulatory region (-422 to -629) which represses the transcription of the TGF-beta(1) gene, the other is a positive regulatory region (-845 to -1550) which enhances the transcription unit efficiently. There is an activating protein-1(AP-1) binding site in the latter region. Mutagenesis in the AP-1 binding sites abolished the Ox-LDL effect. Furthermore, addition of the AP-1 inhibitor curcumin obliterated the Ox-LDL response. The Ox-LDL-induced TGF-beta(1) promoter activation was also prevented by inhibitors of protein kinase C, but not by p38 mitogen-activated protein kinase. Electrophoretic mobility shift assays with oligonucleotides containing AP-1 binding sites showed that Ox-LDL treatment significantly enhanced the binding activity of nuclear proteins of mesangial cells. Supershift assays demonstrated that c-Jun was present in the protein-DNA complexes under stimulation of Ox-LDL. The functional and structural results show that Ox-LDL regulates rat TGF-beta(1) gene expression through AP-1 binding sites and gives rise to the involvement of protein kinase C in Ox-LDL-induced TGF-beta(1) gene expression.


Fatal subcutaneous panniculitis-like T-cell lymphoma gamma/delta subtype (cutaneous gamma/delta T-cell lymphoma): report of a case and review of the literature.
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a distinct type of peripheral T-cell lymphoma, which has gained recognition over the past decade. The disease presents complex clinical, pathologic, and immunohistochemical features, which warrant awareness by dermatologists, dermatopathologists, hematopathologists, hematologists, oncologists, and internists. SPTCL was initially included as a provisional entity in the Revised European-American Lymphoma classification, followed by the European Organization for Research and Treatment of Cancer classification as a primary cutaneous lymphoma, and subsequently as a distinct entity by the World Health Organization classification. It is known that patients diagnosed with SPTCL usually respond poorly to therapy, and the tumor progresses aggressively. Data from recent studies in a series of cases of SPTCL by the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Group have further identified SPTCL as a heterogeneous disease entity, which comprises an alpha/beta subtype (SPTCL-AB) and a gamma/delta subtype (SPTCL-GD). The latter has recently been included in the entity of "cutaneous gamma/delta T-cell lymphoma" by the World Health Organization, Pathology and Genetics of Skin Tumours. The clinical, histologic, and immunophenotypic data, treatment, and prognosis, appear different in the 2 subtypes of SPTCL. We report a case of fatal SPTCL-GD (cutaneous gamma/delta T-cell lymphoma), with detailed clinicopathologic features, immunohistochemical studies, treatment, and clinical course. In view of its aggressive behavior, identification of this disease is critical for proper management and treatment.


Functional cognitive disorders: update on diagnostic status.
Many patients referred to cognitive disorders clinics are not found to have evidence of any neurological disorder(s) to account for their symptoms. Many demonstrate incongruence between their subjective cognitive symptoms and preserved social and occupational functions. The term 'functional cognitive disorders' (FCD) has been used to denote this diagnostic category. This article aims to review the current state of knowledge regarding FCD. Studies of FCD are in their infancy, but available evidence suggests positive diagnosis may be made based on typical clinical profiles, including language discourse and simple clinical signs. Concurrent mood disorder and sleep disturbance are common, as well as other functional disorders. Pathogenesis is yet to be determined, but a disorder of metamemory has been suggested.


Prediction of microdissection testicular sperm extraction outcome in men with idiopathic nonobstruction azoospermia.
The aim of the present study is to assess whether the preoperative clinical indicators have an impact on sperm retrieval rate (SRR) in men with idiopathic nonobstructive azoospermia (NOA).We retrospectively studied 241 consecutive men with NOA who underwent microdissection testicular sperm extraction from 2016 to 2019 in the Reproductive Medicine Center, including 154 patients diagnosed with idiopathic NOA. They were grouped according to preoperative indicators, including average testicular volume, follicle-stimulating hormone (FSH), luteinizing hormone, Testosterone (T), and pathology, respectively.The overall SRR was 20.0% (31/155). Men with testicular volume of ≤5 mL had significant higher SRR than men with testes 5 to 10 and ≥10 mL (35.6% vs 12.3%, P = .002; 35.6% vs 16.2, P = .049, respectively). The SRR in men with FSH ≥ 24.8 mIU/mL was significant higher, compared with FSH level of 12.4 to 24.8 mIU/mL (32.6% vs 15.8%, P = .033). Men with Sertoli cell-only had significantly lower SRR than other pathological type (8.1%). Men with an FSH ≥ 24.8 mIU/mL in testicular volume ≤5 mL group had a significantly higher SRR than FSH level of 12.4 to 24.8 mIU/mL in testicular volume of ≤5 to 10 mL group (44.0% vs 11.4%, P = .002). Men with a luteinizing hormone level of 8.6 to 17.2 mIU/mL in testicular volume of 5 to 10 mL group had a poor prognosis, with an SRR of only 6.5%.Severely reduced testicular volume (≤5 mL) and severely increased FSH level (≥24.8 mIU/mL) had the better sperm retrieval outcome, which can be used as independent predictors in men with idiopathic NOA. And a combination of testicular volume and the hormone seemed to be useful in further increase predictive value.


The relevance of traumatic life events in schizophrenia spectrum disorders.
The central goal of this manuscript was to review literature about the interconnections of traumatic life events and symptoms of schizophrenia spectrum of the last 15 years. First of all, the stress-diathesis model and the traumagenic neurodevelopmental model are shortly presented. Psychological effects of traumas and specific psychotic symptoms in connection with traumatic events are discussed. The course of the disease in patients affected by previous traumas and possible mediating factors are also addressed. Studies of both clinical and community samples are cited. It was also our aim to review literature about the neurobiological and neurocognitive processes in people affected by schizophrenia and/or traumatic life events. The role of prefrontal and medial temporal regions are explored with a special emphasis on contextual memory and hippocampal functioning. Finally, the possible effects of exploring traumatic life events on the treatment of schizophrenia are discussed.


Mitotic aneuploidy as a possible mechanism for tumour promoting activity in bile acids.
A range of conjugated and free bile acids were assayed for their ability to induce a variety of genetic endpoints in growing cells of yeast. None of the bile acids showed any activity in assays for the induction of mitotic crossing-over and mutation whereas the free bile acids lithocholic, chenodeoxycholic, deoxycholic and cholic acid were potent inducers of mitotic chromosome aneuploidy. In contrast, both conjugated bile acids, taurodeoxycholic and glycodeoxycholic lacked the ability to induce mitotic aneuploidy. When the potency of the free bile acids were compared, lithocholic and chenodeoxycholic acids showed higher levels of induction of mitotic aneuploidy per lethal event compared with cholic and deoxycholic acids. In view of the previously observed correlation between the ability of a chemical to induce chromosome aneuploidy and tumour promotional activity, the results indicate that the levels of free bile acids in the colon may be significant factors in the etiology of colonic cancer.


Purpura fulminans in a hyposplenic patient arising from pneumococcal sinusitis.
We report a previously healthy woman in her 50s who presented with sepsis, rapidly progressive purpuric rash and disseminated intravascular coagulation. She was diagnosed with acute infective purpura fulminans due to invasive pneumococcal infection likely secondary to sinusitis. Our case report discusses our initial diagnostic uncertainty and approach in investigating and treating such a critically unwell patient.


Elevated expressions of SHP2 and GAB2 correlated with VEGF in eutopic and ectopic endometrium of women with ovarian endometriosis.
Aims: Protein tyrosine phosphatase Src-homology-2-domain-containing phosphatase 2 (SHP2) and adaptor protein Grb2-associated binding protein 2 (GAB2) can bind to each other in various signal transduction. However, the expression of SHP2 and GAB2 have not been investigated in endometriosis. The aim of the study was to evaluate the expressions of SHP2 and GAB2, and explore the correlation with Ki67 and VEGF in ovarian endometriosis.Materials and methods: The protein expressions and localizations were assessed immunohistochemically in ectopic, eutopic endometrium and normal endometrium from patients with (n = 30) and without (n = 30) ovarian endometriosis.Results: SHP2 was mainly present in the endometrial glandular epithelium, with increased expression in eutopic endometrium and even higher expression in ectopic endometrium compared to control endometrium (p < .05). GAB2 was immunolocalized in endometrial epithelium and stroma, increasing its expression from control endometrium to eutopic and ectopic endometrium (p < .05). Positive correlation was found between SHP2 and GAB2 in endometrium (p < .01). SHP2 and GAB2 both positively correlated with VEGF (p < .05), but not Ki67 in endometrium.Conclusions: We provide the first evidence that the protein expressions of SHP2 and GAB2 were elevated in ectopic and eutopic endometrium, suggesting GAB2-SHP2 axis regulating VEGF might contribute to the pathomechanism of endometriosis.


Translation of messenger RNA from rat epididymis and identification of poly(A)RNA coding for acidic epididymal glycoprotein.
Different proteins are secreted by the various regions of rat epididymis. We have examined the messenger RNA dependence of this varied gene expression by cell-free translation of poly(A)RNA extracts from initial segment, caput plus corpus, and cauda. Labeled translation products were analyzed by polyacrylamide gel electrophoresis under denaturing conditions. Poly(A)RNA from initial segment coded for several unique bands of labeled protein, including a 23,000 MW protein that may correspond to an initial segment protein reported previously to be regulated by testicular fluid factors. Messenger RNA encoding 20,000 MW protein believed to be alpha-lactalbumin, was most abundant in caput but also present in initial segment. Acidic epididymal glycoprotein (AEG) was identified previously by immunoperoxidase staining in epithelial cells of caput, corpus, and cauda. AEG was not readily identified on electrophoresis of total translated proteins, but when concentrated by immunoprecipitation with purified AEG antibody prior to electrophoresis, AEG appeared in both caput plus corpus, and in cauda poly(A)RNA translations.


Stability of sensorimotor network sculpts the dynamic repertoire of resting state over lifespan.
Temporally stable patterns of neural coordination among distributed brain regions are crucial for survival. Recently, many studies highlight association between healthy aging and modifications in organization of functional brain networks, across various time-scales. Nonetheless, quantitative characterization of temporal stability of functional brain networks across healthy aging remains unexplored. This study introduces a data-driven unsupervised approach to capture high-dimensional dynamic functional connectivity (dFC) via low-dimensional patterns and subsequent estimation of temporal stability using quantitative metrics. Healthy aging related changes in temporal stability of dFC were characterized across resting-state, movie-viewing, and sensorimotor tasks (SMT) on a large (n = 645) healthy aging dataset (18-88 years). Prominent results reveal that (1) whole-brain temporal dynamics of dFC movie-watching task is closer to resting-state than to SMT with an overall trend of highest temporal stability observed during SMT followed by movie-watching and resting-state, invariant across lifespan aging, (2) in both tasks conditions stability of neurocognitive networks in young adults is higher than older adults, and (3) temporal stability of whole brain resting-state follows a U-shaped curve along lifespan-a pattern shared by sensorimotor network stability indicating their deeper relationship. Overall, the results can be applied generally for studying cohorts of neurological disorders using neuroimaging tools.


Omnibus hypothesis testing in dominance-based ordinal multiple regression.
Often quantitative data in the social sciences have only ordinal justification. Problems of interpretation can arise when least squares multiple regression (LSMR) is used with ordinal data. Two ordinal alternatives are discussed, dominance-based ordinal multiple regression (DOMR) and proportional odds multiple regression. The Q2 statistic is introduced for testing the omnibus null hypothesis in DOMR. A simulation study is discussed that examines the actual Type I error rate and power of Q2 in comparison to the LSMR omnibus F test under normality and non-normality. Results suggest that Q2 has favorable sampling properties as long as the sample size-to-predictors ratio is not too small, and Q2 can be a good alternative to the omnibus F test when the response variable is non-normal.


Quality Improvement for Outpatient COVID-19 Infection Control.
Background To stop the spread of COVID-19 in outpatient primary care clinics, infection control strategies were needed including social distancing and masking in Fall 2020. Studies show a significant decrease in COVID-19 transmission when healthcare professionals comply with preventive measures. We tested whether an educational video would improve compliance to infection control behaviors quickly. Objective To improve COVID-19 infection control compliance in clinical staff at an outpatient federally qualified health center (FQHC) family medicine residency clinic with quality improvement (QI) tools. Methods On-line surveys assessed medical assistants' (MAs), residents', and attending physicians' before and after an educational video intervention to assess knowledge of and compliance with social distancing and masking guidelines. Independent observed compliance assessments before and after the educational video were used to confirm the self-reported compliance. Results The pre- and post-intervention surveys were completed by 49% (37/76) and 62% (47/76) of participants, respectively. Self-reported knowledge and compliance showed no significant change over time. Observed compliance, however, from pre (n = 667) to post (n = 1132) intervention improved for both masking (p < 0.001) and social distancing (p < 0.001). Conclusion An educational video regarding COVID-19 infection control was effective in improving compliance in an outpatient clinic in an underserved, urban setting. While building these new behavioral habits, however, self-report may not be as accurate as observational assessments. Since this intervention was implemented prior to the COVID-19 fall surge and introduction of mass vaccinations, the educational intervention may have improved behavioral compliance with COVID-19 protocols later in the pandemic.


Nd/TiO2 Anatase-Brookite Photocatalysts for Photocatalytic Decomposition of Methanol.
Neodymium enriched TiO2 anatase-brookite powders were prepared by unconventional method via using pressurized hot fluids for TiO2 crystallization and purification. The photocatalysts were tested in the CH3OH photocatalytic decomposition and they were characterized with respect to the textural (nitrogen adsorption), structural (XRD, XPS, and Raman spectroscopies), chemical (XRF), and optical (DR UV-Vis spectroscopy) and photoelectrochemical measurement. All prepared materials were nanocrystalline, had biphasic (anatase- brookite) structure and relatively large specific surface area (125 m2.g-1). The research work indicates that the doping of neodymium on TiO2 photocatalysts significantly enhances the efficiency of photocatalytic reaction. The photocatalytic activity increased with increasing portion of hydroxyl oxygen to the total amount of oxygen species. It was ascertained that the optimal amount of 1 wt% Nd in TiO2 accomplished the increasing of hydrogen production by 70% in comparison with pure TiO2. The neodymium doped on the titanium dioxide act as sites with accumulation of electrons. The higher efficiency of photocatalytic process was achieved due to improved electron-hole separation on the modified TiO2 photocatalysts. This result was confirmed by electrochemical measurements, the most active photocatalysts proved the highest photocurrent responses.


Using Distance Communication for the User-Centered Development of a Smartphone-Based Serious Game for Children With Type 1 Diabetes: Participatory Design Approach.
The complications of type 1 diabetes (T1D) can be delayed or prevented in children with T1D who receive proper self-management education. Smartphone-based serious games are increasingly being used as an effective tool for teaching self-management. When developing a serious game, it is important that the development process be user-centered. Traditionally, different face-to-face methods have been used when children participate in the development process. However, face-to-face data collection is not always feasible. In such situations, distance communication can be used when developing a serious game. The objective of this study is to develop a user-centered smartphone-based serious game that teaches self-management focused on carbohydrate intake in children aged 8-14 years with T1D using distance communication in both the development and evaluation of the game. The development and evaluation of a smartphone-based serious game prototype was inspired by the Lean principles, and a user-centered approach was applied. The development process included 1 expert interview and design workshops with children with T1D. On the basis of the interview and design workshop results, a serious game prototype was developed using Microsoft PowerPoint. The evaluation of the serious game prototype included an interview with a dietitian and a playtest with children with T1D. All data were collected using distance communication. A user-centered smartphone-based serious game prototype was developed and evaluated. The expert interview with the dietitian formed the basis for the learning outcomes in the game. Four children and their parents contributed to the preferences, needs, requirements, and ideas for selected parts of the game design. The dietitian evaluated the prototype positively and validated its content and accuracy. The serious game prototype was well-received by the children and their parents during the playtest. The serious game prototype was perceived as a useful and engaging way to learn. However, the difficulty level was not appropriate, and the information was too basic for participants who had been diagnosed over a year ago. The use of digital communication platforms did not cause any problems. The smartphone-based serious game prototype has the potential to be a useful and attractive tool for teaching disease self-management. The use of distance communication proved to be a useful approach in the development of a serious game.


[Risk factors for non-sentinel lymph node metastasis in patients after neoadjuvant chemotherapy].
To evaluate the risk factors for non-sentinel lymph node (NSLN) metastasis in patients after neoadjuvant chemotherapy (NCT) so as to develop a new predictive model. A total of 512 consecutive patients with metastasis in sentinel lymph node (SLN) on neoadjuvant chemotherapy between August 2005 and March 2013 were recruited to evaluate the factors affecting the involvement of NSLN. Logistic regression analysis was performed to construct a predictive model. There were 115 (22.4%) patients with metastasis in NSLN after axillary lymph node dissection. Univariate analysis showed that tumor size, number of positive SLN, hormone receptor (HR), micrometastasis and clinical response of primary tumor after NCT were associated with the involvement of NSLN (P < 0.05). Multivariate analysis indicated that tumor size, number of positive SLN, HR, micrometastasis and clinical response of primary tumor after NCT were significant independent predictors for NSLN metastasis. Area under the curve was 0.779. Tumor size, number of positive SLN, HR, micrometastasis and clinical response of primary tumor after NCT were significant independent predictors for NSLN metastasis in patients after NCT. The new model is to be further validated.


Primary small bowel volvulus in Nepal.
Small bowel volvulus is a rare cause of intestinal obstruction. Primary small bowel volvulus occurs without any predisposing cause. It is rare in Western countries but common in Africa and Asia. It is the most common cause of bowel obstruction in Nepal (excluding incarcerated external hernias). Early diagnosis and management is essential to avoid infarction of bowel. Persistent central abdominal pain is characteristic. There is no single specific diagnostic clinical sign or abnormality in laboratory or radiological findings. There is no role of conservative management and, in suspected cases, early laparotomy should be done to avoid bowel infarction. In follow-up patients may present with stricture formation or recurrence of bowel volvulus.


Single-molecule probes of lipid membrane structure.
Biological membranes are highly heterogeneous structures that are thought to use this heterogeneity to organize and modify the function of membrane constituents. Probing membrane organization, structure, and changes therein are crucial for linking structural metrics with function in biological membranes. Here we report the use of single-molecule fluorescence studies to measure membrane structure at the molecular level. Several groups have shown that polarized total internal reflection fluorescence microscopy using p-polarized excitation can reveal single-molecule orientations when spherical aberrations are introduced into the optics train. We use this approach to measure the orientation of fluorescent lipid analogs doped into Langmuir-Blodgett films of DPPC and arachidic acid. We compare two commonly used fluorescent lipid analogs, BODIPY-PC and DiIC18, which have their fluorophores located in the tailgroup and headgroup, respectively. We find the tilt orientation of BODIPY-PC is very sensitive to the surface pressure at which DPPC films are transferred onto the substrate. At low surface pressures, the tailgroups are largely lying in the plane of the filmand evolve to an orientation normal to the surface as pressure is increased. For DiIC18, however, no evolution in orientation with surface pressure is observed, which is consistent with the headgroup located fluorophore being less sensitive to changes in membrane packing. Single-molecule orientation measurements of DiIC18 in multilayer films of arachidic acid are also measured and compared with previous bulk measurements. Finally, single-molecule measurements are utilized to reveal the ordering induced in DPPC monolayers following the addition of cholesterol.


[Monoclonal antibodies and therapeutics].
More than 25 years after their discovery, monoclonal antibodies are now the most rapid expanding pharmaceutical viable drugs in clinical trials. The emergence of these antibodies was made possible by the development of genetic recombinant techniques. It is now possible to obtain engineered antibodies: chimearic or humanized or fully human monoclonal antibodies via the use of phage display technology or of transgenic mice. These antibodies are tolerable to the human immune system and eleven have been approved for therapeutic by the US Food and Drug Administration (FDA), the majority of them in the past four years. At least an additional 400 monoclonal antibodies are in clinical trials to treat cancer, transplant rejection or to combat autoimmune or infectious diseases. Important advances have been made in the design of highly specific fragment antibodies, fused or not with drugs or radioisotopes, and in the large industrial scale production with different expression systems (bacteria, yeasts, mammalian cells and transgenic plants and animals). In the next future new molecular promising strategies will enhance affinity, stability and expression levels and reduce the price of these engineering monoclonal to permit their use to treat a large number of diseases.


Prenatal exposure to bisphenol A impacts midbrain dopamine neurons and hippocampal spine synapses in non-human primates.
Prevalent use of bisphenol-A (BPA) in the manufacture of resins, plastics and paper products has led to frequent exposure of most people to this endocrine disruptor. Some rodent studies have suggested that BPA can exert detrimental effects on brain development. However as rodent models cannot be relied on to predict consequences of human exposure to BPA during development, it is important to investigate the effects of BPA on non-human primate brain development. Previous research suggests that BPA preferentially targets dopamine neurons in ventral mesencephalon and glutamatergic neurons in hippocampus, so the present work examined the susceptibility of these systems to low dose BPA exposure at the fetal and juvenile stages of development in non-human primates. Exposure of pregnant rhesus monkeys to relatively low levels of BPA during the final 2 months of gestation, induced abnormalities in fetal ventral mesencephalon and hippocampus. Specifically, light microscopy revealed a decrease in tyrosine hydroxylase-expressing (dopamine) neurons in the midbrain of BPA-exposed fetuses and electron microscopy identified a reduction in spine synapses in the CA1 region of hippocampus. In contrast, administration of BPA to juvenile vervet monkeys (14-18 months of age) was without effect on these indices, or on dopamine and serotonin concentrations in striatum and prefrontal cortex, or on performance of a cognitive task that tests working memory capacity. These data indicate that BPA exerts an age-dependent detrimental impact on primate brain development, at blood levels within the range measured in humans having only environmental contact with BPA.


Plasma-based testing as a new paradigm for clinical testing in hematologic diseases.
Recent advances in molecular biology have paved the way for the detection of minute quantities of cellular components with robust assays that are amenable for use in clinical laboratories. This review discusses the recently developed series of plasma-based assays that are changing the testing paradigm for hematologic diseases. These tests are based on the concept that a high turnover of neoplastic hematologic cells, relative to normal cells, enriches plasma with tumor-specific DNA, RNA and protein. Plasma-based testing promises to reduce the need for bone marrow biopsy, allow for more frequent and accurate monitoring of changes in bone marrow, allow the detection of more aggressive subclones of the malignant cells and provide a more quantitative means to measure the load of the malignant clone. We present data demonstrating that plasma, in some situations, allows even more sensitive detection than bone marrow cells. Moreover, the lessened impact of dilution by normal cells in plasma permits a distinction between homozygous and hemizygous abnormalities. Unlike solid tumors, currently available data suggest that in hematologic diseases, plasma is superior to cells in detecting molecular abnormalities.


Isolated low second-trimester maternal serum beta-human chorionic gonadotropin is not associated with adverse pregnancy outcome.
We investigated whether low human chorionic gonadotropin from maternal serum screening is associated with adverse pregnancy outcome. Women between 15 and 20 completed weeks of gestation who had a maternal serum screen performed from June 1999 to November 2001 were studied. Cases included women with human chorionic gonadotropin values of <or=0.5 multiples of the median, alpha-fetoprotein values of >0.5 and <2.0 multiples of the median, and estriol values of >0.6 and <2.0 multiples of the median. Control subjects were selected randomly from the population of women with normal values for all three analytes. There were 146 case subjects and 292 control subjects. There was no increased risk in the study group compared with the control subjects for preterm delivery, intrauterine fetal death, low birth weight, abruptio placentae, preeclampsia, or preterm premature rupture of membranes. An isolated low human chorionic gonadotropin level from second-trimester maternal serum screening is not associated with adverse pregnancy outcome.


The false fontanel.
In the neonate, palpation of the anterior fontanel is recognized as a simple and reliable means for estimating intracranial pressure. With closure of the fontanel this aspect of the clinical examination is lost. The authors report a series of 15 shunted infants and children in whom a false fontanel was created by making a 2-cm craniectomy in the right parietal region and excising the underlying internal pericranium. This produces a cranial opening which, like the anterior fontanel, can be used for palpation and real-time ultrasound imaging of the brain. By removing the internal pericranium, reossification of the defect is delayed by more than 12 months. Sparing the dura propria avoids the risks of cerebrospinal fluid leak or brain herniation into the cranial window. This procedure is reported to be simple, reliable, and of value in assessing shunt function in hydrocephalic infants and young children. An illustrative case report is presented.


Influenza A virus utilizes suboptimal splicing to coordinate the timing of infection.
Influenza A virus is unique as an RNA virus in that it replicates in the nucleus and undergoes splicing. With only ten major proteins, the virus must gain nuclear access, replicate, assemble progeny virions in the cytoplasm, and then egress. In an effort to elucidate the coordination of these events, we manipulated the transcript levels from the bicistronic nonstructural segment that encodes the spliced virus product responsible for genomic nuclear export. We find that utilization of an erroneous splice site ensures the slow accumulation of the viral nuclear export protein (NEP) while generating excessive levels of an antagonist that inhibits the cellular response to infection. Modulation of this simple transcriptional event results in improperly timed export and loss of virus infection. Together, these data demonstrate that coordination of the influenza A virus life cycle is set by a "molecular timer" that operates on the inefficient splicing of a virus transcript.


[The antinociceptive effect of tramal when combined with nonsteroidal anti-inflammatory preparations].
The antinociceptive effect of tramal and its combinations with nonsteroidal anti-inflammatory drugs (ortophen, indomethacin, naproxen, acetylsalicylic acid, and ibuprofen) was studied in 110 male albino rats on models of electric and thermal stimulation. Possessing their own antinociceptive activity, nonsteroidal anti-inflammatory drugs potentiated the analogous effect of tramal. In vitro tramal was intensively demethylated by the rat liver microsomal fraction. In therapeutic concentrations ortophen and naproxen suppressed the rate of tramal demethylation by the rat microsomes. The potentiating effect of nonsteroidal anti-inflammatory drugs in relation to tramal is apparently connected with the delay in its biotransformation and conversion to inactive metabolites.


Design of a simple and low-cost solid-state ultra-fast high-voltage switch.
Ultra-fast high-voltage switches (UFHVSs) are a core component of time-of-flight mass spectrometers for realizing high accuracy ion acceleration, deceleration, and temporal focusing. The desirable features of high performance UFHVSs include a large range of adjustability of pulse width, a high maximum output amplitude, and minute rising and falling times. Besides the simplicity of the driver circuit, the total cost of the whole device is also critical to its practical applications. In this work, we present a low-cost and easy-fabrication 5000 V bipolar solid-state UFHVS for a high-resolution mass spectrometer. A double-pulse transformer isolates the circuit's high- and low-voltage sides and synchronously drives series-connected cascode SiC FETs to form its push-pull topology. This scheme allows transmitting drive signals with long widths but without the magnetic saturation of the transformer. Testing results show that output pulses reach a maximum voltage of 5000 V and a width of 150 µs, with rising and falling times of 8.5 and 18.3 ns, respectively. More importantly, they have nearly no voltage decay.


Delayed diagnosis for undescended testes.
Delayed diagnosis of undescended testes is a major problem. A retrospective review of 298 testes units was performed to assess the age at referral, age at operation, complications and final outcome. The mean age at referral was 57 months. Only 24% of cases were operated below 2 years. A similar pattern of delayed orchidopexy has been reported by many other centres. As orchidopexy is recommended soon after 6-7 months of age, there is an urgent need for increased awareness of undescended testes and its consequences at all levels of child health care.


Tibetan immigrants in India.
"This paper documents the current evidence of the state of the Tibetan society in India with special reference to the trends in social transformation, livelihood patterns and cultural adaptation to a geographically alien environment....Three-and-a-half decades of living in India [have] demonstrated how a culture group can survive by carving out ecological niches in ethnically segregated social space and yet adapt to a new cultural environment without losing its identity."


TLR9 drives the development of transitional B cells towards the marginal zone pathway and promotes autoimmunity.
Maturation of B cells depends on environmental stimuli. Peripheral immature B cells develop into follicular pathway when antigenic stimulation is combined with T cell signals. Here, we wished to identify stimuli contributing to the development into marginal zone B cells known to be involved in autoimmune response. We found that TLR9 stimulation of transitional B cells induces proliferation and specific maturation into CD24(-) CD38(+) CD21(high) CD23(low) IgM(high) IgD(low) and Notch2(high) B cells characteristics of marginal zone B cells. Terminal differentiation into antibody-secreting cell associated with isotype switch commitment is also triggered which leads to a striking production of autoantibodies. Interestingly, mature B cells do not differentiate into marginal zone pathway following TLR9 stimulation, nor do transitional B cells under antigenic and T cell combined signals. These results suggest that transitional B cells are specifically sensitive to TLR9 stimulation to produce autoreactive marginal zone B cells.


Association of microRNA-933 variant with the susceptibility to gastric cancer.
Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRs) have been shown to be associated with susceptibility to several types of human cancer. However, the association of miR-933 rs79402775 with gastric cancer (GC) has not been explored. The association between rs79402775 in miR- 933 and the risk of GC was explored in Chinese population based on MassARRAY technology. A total 374 GC patients and 999 cancer-free controls were enrolled in this study. Compared with the wild-type GG, GA genotype was associated with a significantly decreased risk of GC (OR=0.542, 95% CI=0.299-0.983, p=0.044) in female subjects. Moreover, the variant was also associated with the expression of alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA). miR-933(rs79402775) may contribute to decreased susceptibility to GC and this SNP could be developed as a biomarker for GC prognosis.


Analysis of Sheep and Goat IAPP Provides Insight into IAPP Amyloidogenicity and Cytotoxicity.
Human islet amyloid polypeptide (hIAPP) plays a role in glucose regulation but forms pancreatic amyloid deposits in type 2 diabetes, and that process contributes to β-cell dysfunction. Not all species develop diabetes, and not all secrete an IAPP that is amyloidogenic in vitro under normal conditions, a perfect correlation currently exists between both. Studies of IAPPs from such organisms can provide clues about the high amyloidogenicity of hIAPP and can inform the design of soluble analogues of hIAPP. Sheep and goat IAPP are among the most divergent from hIAPP, with 13 and 11 substitutions, respectively, including an unusual Tyr to His substitution at the C-terminus. The properties of sheep and goat IAPP were examined in solution and in the presence of anionic vesicles, resulting in no observed amyloid formation, even at increased concentrations. Furthermore, both peptides are considerably less toxic to cultured β-cells than hIAPP. The effect of the Y37H replacements was studied in the context of hIAPP, as was a Y37R substitution. Buffer- and salt-dependent effects were observed. There was little impact on the time to form amyloid in phosphate-buffered saline; however, a significant deceleration was observed in Tris buffer, and amyloid formation was slower in the absence of added salt. The Y37H substitution had little impact on toxicity, while the Y37R replacement led to a 30% decrease in toxicity compared with that of hIAPP. The implications for the amyloidogenicity of hIAPP and the design of soluble analogues of the human peptide are discussed.