Parameters Optimization of Laser-Grinding Chain for Processing Groove of 2.5-Dimensional C/SiC Composites.
Aiming at problems such as poor precision of laser processing C/SiC composites, low efficiency of grinding C/SiC composites, and serious wear of grinding wheel, a method of laser-grinding chain processing C/SiC composite groove was proposed in this paper. The method combined the high efficiency characteristic of laser ablating and the high precision characteristic of grinding. The relationship between laser processing parameters and the characteristics of ablative grooves was investigated, and the appropriate laser processing parameters were optimized, and then, to further improve the processing quality of the grooves, the grinding parameters optimization experiments of the grooves of C/SiC composites were carried out. The results showed that the C/SiC composites could be quickly removed by laser processing, and the grooves with relatively good size and shape accuracy could be obtained by laser parameters optimization experiments, but the side wall of the groove still had a certain inclination and the surface quality of the groove was yet poor; meanwhile, the size accuracy, shape accuracy, and surface quality of the grooves were greatly improved by further grinding. In addition, then, through the laser and grinding optimization experiments, the optimized parameters were obtained, where the laser power was 80 W, the scanning speed was 300 mm/s, the scanning frequency was 50 kHz, the scanning spacing was 25 μm, the depth of cut was 30 μm, the liner speed of wheel was 62.832 m/min, and the feed speed was 10 mm/min. With these parameters, the time used to process the groove with the laser-grinding chain was about 23/40 of the grinding process, and the quality of grooves could be guaranteed. Therefore, combined with the optimized process parameters, the laser-grinding chain processing scheme could be used to achieve high efficiency and precision grinding of C/SiC composite grooves.


Inotropic Effects of Experimental Hyperthermia and Hypothermia on Left Ventricular Function in Pigs-Comparison With Dobutamine.
The results from the recent Targeted Temperature Management trial raised the question whether cooling or merely the avoidance of fever mediates better neurologic outcome in resuscitated patients. As temperature per se is a major determinant of cardiac function, we characterized the effects of hyperthermia (40.5°C), normothermia (38.0°C), and mild hypothermia (33.0°C) on left ventricular contractile function in healthy pigs and compared them with dobutamine infusion. Animal study. Large animal facility, Medical University of Graz, Graz, Austria. Nine anesthetized and mechanically ventilated closed-chest Landrace pigs (67 ± 2 kg). Core body temperature was controlled using an intravascular device. At each temperature step, IV dobutamine was titrated to double maximum left ventricular dP/dt (1.8 ± 0.1 µg/kg/min at normothermia). Left ventricular pressure-volume relationships were assessed during short aortic occlusions. Left ventricular contractility was assessed by the calculated left ventricular end-systolic volume at an end-systolic left ventricular pressure of 100 mm Hg. Heart rate (98 ± 4 vs 89 ± 4 vs 65 ± 2 beats/min; all p < 0.05) and cardiac output (6.7 ± 0.3 vs 6.1 ± 0.3 vs 4.4 ± 0.2 L/min) decreased with cooling from hyperthermia to normothermia and mild hypothermia, whereas left ventricular contractility increased (left ventricular end-systolic volume at a pressure of 100 mm Hg: 74 ± 5 mL at hyperthermia, 52 ± 4 mL at normothermia, and 41 ± 3 mL at mild hypothermia; all p < 0.05). The effect of cooling on left ventricular end-systolic volume at a pressure of 100 mm Hg (hyperthermia to normothermia: -28% ± 3% and normothermia to mild hypothermia: -20% ± 5%) was of comparable effect size as dobutamine at a given temperature (hyperthermia: -28% ± 4%, normothermia: -27% ± 6%, and mild hypothermia: -27% ± 9%). Cooling from hyperthermia to normothermia and from normothermia to mild hypothermia increased left ventricular contractility to a similar degree as a significant dose of dobutamine in the normal porcine heart. These data indicate that cooling can reduce the need for positive inotropes and that lower rather than higher temperatures are appropriate for the resuscitated failing heart.


Synthesis and properties of N-(aminoalkyl)-4-acetyl-3,5-dimethylpyrrole-2-carboxamides hydrochlorides.
A series of N-(aminoalkyl)-4-acetyl-3,5-dimethylpyrrole-2-carboxamides hydrochlorides have been prepared and evaluated as cytostatic agents. General procedures were developed for constructing aminoalkyl chains on the 4-acetylpyrrole-2-carboxylic acid nuclei, utilizing 2-pyridone. The results of the preliminary biological activity have been mentioned.


Cutaneous granulomatosis and combined immunodeficiency revealing Ataxia-Telangiectasia: a case report.
Ataxia-telangiectasia (A-T) is a complex multisystem disorder characterized by progressive neurological impairment, variable immunodeficiency and oculo-cutaneous telangiectasia. A-T is a member of chromosomal breakage syndromes and it is caused by a mutation in the ataxia-telangiectasia mutated (ATM) gene. Because of a wide clinical heterogeneity, A-T is often difficult to diagnose in children. We report an unusual case of a 3-year-old boy affected by A-T who presented exclusively with extensive cutaneous granulomatosis and severe combined immunodeficiency, without neurological abnormalities, at the time of diagnosis. This case clearly emphasizes the variable presentation of A-T syndrome and highlights the difficulties in the early diagnosis of A-T. A-T should be considered in children with evidence of combined humoral and cellular immunodeficiency associated with unexplained skin granulomatous lesions, even in the absence of the classic features of this syndrome.


RNA sequencing of the exercise transcriptome in equine athletes.
The horse is an optimal model organism for studying the genomic response to exercise-induced stress, due to its natural aptitude for athletic performance and the relative homogeneity of its genetic and environmental backgrounds. Here, we applied RNA-sequencing analysis through the use of SOLiD technology in an experimental framework centered on exercise-induced stress during endurance races in equine athletes. We monitored the transcriptional landscape by comparing gene expression levels between animals at rest and after competition. Overall, we observed a shift from coding to non-coding regions, suggesting that the stress response involves the differential expression of not annotated regions. Notably, we observed significant post-race increases of reads that correspond to repeats, especially the intergenic and intronic L1 and L2 transposable elements. We also observed increased expression of the antisense strands compared to the sense strands in intronic and regulatory regions (1 kb up- and downstream) of the genes, suggesting that antisense transcription could be one of the main mechanisms for transposon regulation in the horse under stress conditions. We identified a large number of transcripts corresponding to intergenic and intronic regions putatively associated with new transcriptional elements. Gene expression and pathway analysis allowed us to identify several biological processes and molecular functions that may be involved with exercise-induced stress. Ontology clustering reflected mechanisms that are already known to be stress activated (e.g., chemokine-type cytokines, Toll-like receptors, and kinases), as well as "nucleic acid binding" and "signal transduction activity" functions. There was also a general and transient decrease in the global rates of protein synthesis, which would be expected after strenuous global stress. In sum, our network analysis points toward the involvement of specific gene clusters in equine exercise-induced stress, including those involved in inflammation, cell signaling, and immune interactions.


Reproducibility of tooth tapping rhythm in young and elderly dentate subjects.
The reproducibility of tooth tapping frequencies was measured in young and elderly dentate subjects. Six rates of tapping, i.e. 40, 60, 90, 120, 160 and 200 times per min, were practised to the accompaniment of a metronome for 15 s before recording. After a 15-s break, subjects were asked to reproduce the same rate of tapping without metronome accompaniment, and these movements were recorded. It was determined that the young subjects regulated tooth tapping frequencies by controlling velocity of mandibular movement. On the other hand, the elderly subjects regulated tooth tapping frequency by controlling opening width.


Microsatellite marker development and analysis in the eastern oyster (Crassostrea virginica): confirmation of null alleles and non-Mendelian segregation ratios.
Eighteen microsatellite markers were developed for the Crassostrea virginica nuclear genome, including di-, tri-, and tetranucleotide microsatellite repeat regions that included perfect, imperfect, and compound repeat sequences. A reference panel with DNA from the parents and four progeny of 10 full-sib families was used for a preliminary confirmation of polymorphism at these loci and indications of null alleles. Null alleles were discovered at three loci; in two instances, primer redesign enabled their amplification. Two to five representative alleles from each locus were sequenced to ensure that the targeted loci were amplifying. The sequence analysis revealed not only variation in the number of simple sequence repeat units, but also polymorphisms in the microsatellite flanking regions. A total of 3626 bp of combined microsatellite flanking region from the 18 loci was examined, revealing indels as well as nucleotide site substitutions. Overall, 16 indels and 146 substitutions were found with an average of 4.5% polymorphism across all loci. Eight markers were tested on the parents and 39-61 progeny from each of four families for examination of allelic inheritance patterns and genotypic ratios. Twenty-six tests of segregation ratios revealed eight significant departures from expected Mendelian ratios, three of which remained significant after correction for multiple tests. Deviations were observed in both the directions of heterozygote excess and deficiency.


[Multilingual children and language impairment].
Multilingual children and language impairment Abstract. For many children with a migration background, difficulties acquiring their second language skills influences their educational success. Because of the wide range of languages and their varieties, which are not described linguistically in detail, development of reliable and valid assessment procedures is hindered. This results in a diagnostic dilemma, as children who have problems learning their second language, along with many other reasons, have to be distinguished from children suffering from a specific language impairment (SLI). Children with migration background may show linguistic profiles which superficially resemble those of children with SLI. The current paper constitutes a selective review of relevant literature and offers suggestions for meeting those respective challenges. It is assumed that the prevalence for clinically relevant language disorder is the same in multilingual as in monolingual children. Also, multilingual children like monolingual children can show subtle cognitive weaknesses. The relevance of language disorder in psychiatrically ill multilingual and monolingual children is well known and has to be considered in the context of a comprehensive assessment. For those children with a migration background who face more pronounced problems acquiring their second language skills, language assessment in their mother tongue is essential.


Clinical analysis of aqueductal stenosis in patients with hydrocephalus in a Kenyan setting.
Aqueductal stenosis is the commonest cause of congenital hydrocephalus. The scope of this paper is to highlight the disease burden of hydrocephalus attributed to aqueductal stenosis which still remains unknown in our setting. In a descriptive cross-sectional study, 258 records of patients diagnosed with hydrocephalus were analyzed after ethical approval from Kenyatta National Hospital- University of Nairobi (KNH-UON) ethics and research committee from January 2010 to May 2016. Patients with a diagnosis of hydrocephalus due to aqueductal stenosis were included in this study. Patients age, sex, mode of delivery, associated comorbidities, presenting complaints, neurosurgical intervention performed, Kafarnosky score were recorded. Data were divided into 2 sets based on the patient's age i.e. whether < 1 year or > 12 years. Data were recorded on google data collection form and analyzed using Google spreadsheets. Out of 258 cases of hydrocephalus, 52 had aqueductal stenosis. Male to female sex ratio for this condition was 3:2. There were 25 cases < 1year and 27 cases > 12 years old who were diagnosed with hydrocephalus due to aqueductal stenosis. Associated conditions were bilateral congenital talipes equinovarus, spina bifida, Arnold Chairi malformations, meningitis and HIV. The presenting complaints differed according to the age groups. Neurosurgical interventions included Endoscopic Third Ventriculostomy (ETV) in 21 cases, insertion of Ventriculoperitoneal (VP) shunt and ETV were done in 3 cases while the rest had only insertion of VP shunt. The Kafanosky score improve from < 50 pre-op to 19 cases achieving a score of 100, six months post-op. Aqueductal stenosis contributes a significant burden of morbidity in patients with hydrocephalus. Clinical presentation differs according to patients age. Accurate diagnosis and treatment remain a cardinal to improving patient outcome.


Development and optimization of sustained release triptolide microspheres.
Rheumatoid arthritis is considered a chronic systemic autoimmune disorder that may cause joint destruction. Triptolide, an active component isolated from Tripterygium wilfordii Hook.f., is considered to have promising potential for clinical use in treating rheumatoid arthritis. However, its clinical application has been limited by the narrow therapeutic window, side effects associated with plasma drug fluctuations, low oral bioavailability, and poor patient compliance with the long and frequent dosing regimen. An extended drug release preparation may address these limitations. The aim of this work was therefore to develop, formulate and optimize sustained release triptolide microspheres with poly (lactide-co-glycolide) (PLGA). Triptolide-loaded microspheres were prepared using PLGA as the matrix polymer, dichloromethane as the oil phase, and polyvinyl alcohol (PVA) as the matrix forming emulsifier. An oil-in-water (O/W) emulsion solvent evaporation technique was utilized to prepare the microspheres. Surface response methodology (RSM) coupled with central composite design (CCD) was used to optimize the formulation and a total of twenty formulations were prepared. PVA concentration (X1), PLGA concentration (X2), and theoretical drug content (X3) were selected as independent variables; and drug content (Y1), encapsulation efficiency (Y2), mean diameter (Y3) and the initial release during the first day (Y4) were taken as the response variables. The optimized formulation showed mean diameter of 42.36 μm, drug content of 7.96%, encapsulation efficiency of 80.16% and an initial release of 14.48%. The prepared microspheres exhibited a sustained release profile of triptolide in vitro over 4 weeks, which was wellfitted with a Korsmeyer-Peppas equation. However, the initial drug release (~14%) of triptolide-loaded microspheres was very high and should be specifically investigated in future studies. The results indicate that long-term sustained release microspheres of triptolide can be considered a strategy to overcome the low bioavailability and poor patient compliance with conventional triptolide tablets. The issue of initial burst release and in vivo evaluations should be specifically investigated in the future.


A 3-Mbp fragment on rat chromosome 1 affects susceptibility both to stroke and kidney injury under salt loading in the stroke-prone spontaneously hypertensive rat: a genetic approach using multiple congenic strains.
We have previously reported that a major quantitative trait locus (QTL) responsible for susceptibility to salt-induced stroke in the stroke-prone spontaneously hypertensive rat (SHRSP) is located in a 3-Mbp region on chromosome 1 covered by SHRSP.SHR-(D1Rat23-D1Rat213)/Izm (termed Pr1.31), a congenic strain with segments from SHRSP/Izm introduced into the stroke-resistant SHR/Izm. Here, we attempted to narrow down the candidate region on chromosome 1 further through analyses of subcongenic strains constructed for the target region. Simultaneously, salt-induced kidney injury was evaluated through the measurement of urinary albumin and the gene expression of renal tubular injury markers (Kim-1 and Clu) to explore a possible mechanism leading to the onset of stroke. All subcongenic strains examined in this study showed lower susceptibility to salt-induced stroke than SHRSP. Interestingly, Pr1.31 had the lowest stroke susceptibility when compared with newly constructed subcongenic strains harboring fragments of the congenic sequence in Pr1.31. Although Kim-1 and Clu expression after 1 week of salt loading in Pr1.31 did not differ significantly from those in SHRSP, the urinary albumin level of Pr1.31 was significantly lower than those of the other subcongenic strains and that of SHRSP. The present results indicated that, although the congenic fragment in Pr1.31 harbored the gene(s) related to salt-induced organ damages, further genetic dissection of the candidate region was difficult due to multiple QTLs suggested in this region. Further analysis using Pr1.31 will unveil genetic and pathophysiological mechanisms underlying salt-induced end organ damages in SHRSP.


Separation and determination of reduced vitamin C in polymerized hemoglobin-based oxygen carriers of the human placenta.
The molybdenum blue method was used to determine the content of reduced vitamin C (Vc) in a solution of polymerized hemoglobin-based oxygen carriers (HBOCs) of the human placenta. The conditions of absorption wavelength, HCl addition, and reaction time, were investigated. The results of validation experiments showed that under the optimized conditions, a standard curve was confirmed with good linearity of 0.9985, for the Vc amount ranging from 0-200 μg. The values for relative standard deviation (RSD) of the precision and repeatability were both below 5%. Vc recovery was in the range of 97-102%. The conclusion could be made that a reduction in Vc content could be tested effectively by the molybdenum blue method.


Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer.
Objectives: Tumor-infiltrating lymphocytes (TILs) have been identified as a significant prognostic indicator of response to neoadjuvant therapy and immunotherapy for triple-negative breast cancer (TNBC) patients. Herein, we aim to assess the association between TIL levels and mammographic features in TNBC patients. Methods: Forty-three patients with surgically proven TNBC who underwent preoperative mammography from January 2018 to December 2018 were recruited. Pyradiomics software was used to extract 204 quantitative radiomics features, including morphologic, grayscale, and textural features, from the segmented lesion areas. The correlation between radiological characteristics and TIL levels was evaluated by screening the most statistically significant radiological features using Mann-Whitney U-test and Pearson correlation coefficient. The patients were divided into two groups based on tumor TIL levels: patients with TIL levels <50% and those with TIL levels ≥50%. The correlation between TIL levels and clinicopathological characteristics was assessed using the chi-square test or Fisher's exact test. Mann-Whitney U-test and Pearson correlation coefficient were used to analyze the statistical significance and Pearson correlation coefficient of clinical pathological features, age, and radiological features. Results: Of 43 patients, 32 (74.4%) had low TIL levels and 11 (25.6%) had high TIL levels. The histological grade of the low TIL group was higher than that of the high TIL group (p = 0.043). The high TIL group had a more negative threshold Ki-67 level (<14%) than the low TIL group (p = 0.017). The six most important radiomics features [uniformity, variance, grayscale symbiosis matrix (GLCM) correlation, GLCM autocorrelation, gray level difference matrix (GLDM) low gray level emphasis, and neighborhood gray-tone difference matrix (NGTDM) contrast], representing qualitative mammographic image characteristics, were statistically different (p < 0.05) among the low and high TIL groups. Tumors in the high TIL group had a more non-uniform density and a smoother gradient of the tumor pattern than the low TIL group. The changes in Ki-67, age, epidermal growth factor receptor, radiomic characteristics, and Pearson correlation coefficient were statistically significant (p < 0.05). Conclusion: Mammography features not only distinguish high and low TIL levels in TNBC patients but also can act as imaging biomarkers to enhance diagnosis and the response of patients to neoadjuvant therapies and immunotherapies.


Increased newborn NICU admission for evaluation of hypoxic-ischemic encephalopathy during COVID-19 pandemic in a public hospital.
Prenatal and perinatal care of pregnant mothers has been adversely affected during the COVID-19 pandemic. Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal death and long-term neurological disabilities. Therapeutic hypothermia is effective for neonatal HIE. This study evaluated the effect of the pandemic on neonatal HIE. This retrospective single-center study compared neonatal HIE evaluation and hypothermia treatment between pre-COVID-19 pandemic (1 January 2018-31 December 2019) and COVID-19 pandemic (1 January 2020-31 December 2021) periods. Infants with abnormal neurological examination and or significant metabolic acidosis were admitted to NICU for evaluation of HIE and therapeutic hypothermia. Demographics, NICU admission and interventions, and neonatal outcomes were compared between infants born during the two periods using χ2, t-test, and Wilcoxon rank-sum test as appropriate. Statistical Process Control charts show the yearly proportion of infants evaluated for HIE and those treated with therapeutic hypothermia. From the pre-pandemic to the pandemic period, the proportion of infants that met HIE screening criteria increased from 13% to 16% (p < 0.0001), the proportion of infants admitted to NICU for HIE evaluation increased from 1% to 1.4% (p = 0.02), and the maternal hypertension rates of the admitted infants increased from 30% to 55% (p = 0.006). There was no difference in the proportions of the infants diagnosed with HIE (0.7% vs. 0.9%, p = 0.3) or treated with therapeutic hypothermia (0.2% vs. 0.3%, p = 0.3) between the two periods. There were no differences in the HIE severity and outcomes of the infants treated with therapeutic hypothermia between the two periods. During the COVID-19 pandemic, we observed a significant increase in NICU admission for HIE evaluation. While we did not find significant increases in neonatal HIE and the need for therapeutic hypothermia, larger studies are needed for a comprehensive assessment of the impact of the COVID-19 pandemic on neonatal HIE.


Chronic cAMP activation induces adipocyte browning through discordant biphasic remodeling of transcriptome and chromatin accessibility.
Adipose tissue thermogenesis has been suggested as a new therapeutic target to promote energy metabolism for obesity and metabolic disease. Cold-inducible thermogenic adipocytes, called beige adipocytes, have attracted significant attention for their potent anti-obesity activity in adult humans. In this study, we identified the mechanisms underlying beige adipocyte recruitment, so-called adipocyte browning, by different stimuli. We generated a new adipocyte cell line with enhanced browning potentials and determined its transcriptomic and epigenomic responses following cAMP (forskolin, FSK) versus PPARγ activation (rosiglitazone). We performed time-course RNA-seq and compared the treatments and in vivo adipocyte browning. We also developed an improved protocol for Assay for Transposase Accessible Chromatin-sequencing (ATAC-seq) and defined changes in chromatin accessibility in a time course. The RNA-seq and ATAC-seq data were integrated to determine the kinetics of their coordinated regulation and to identify a transcription factor that drives these processes. We conducted functional studies using pharmacological and genetic approaches with specific inhibitors and shRNA-mediated knockdown, respectively. FSK, not rosiglitazone, resulted in a biphasic transcriptomic response, resembling the kinetics of in vivo cold-induced browning. FSK promoted tissue remodeling first and subsequently shifted energy metabolism, concluding with a transcriptomic profile similar to that induced by rosiglitazone. The thermogenic effects of FSK were abolished by PPARγ antagonists, indicating PPARγ as a converging point. ATAC-seq uncovered that FSK leads to a significant chromatin remodeling that precedes or persists beyond transcriptomic changes, whereas rosiglitazone induces minimal changes. Motif analysis identified nuclear factor, interleukin 3 regulated (NFIL3) as a transcriptional regulator connecting the biphasic response of FSK-induced browning, as indicated by disrupted thermogenesis with NFIL3 knockdown. Our findings elucidated unique dynamics of the transcriptomic and epigenomic remodeling in adipocyte browning, providing new mechanistic insights into adipose thermogenesis and molecular targets for obesity treatment.


Absorption and scattering of light from ensembles of randomly oriented aggregates.
This paper presents one approach to the absorption and scattering of light from aggregates of primary particles. The primary particles are sphere-like and small compared to the wavelength, whereas the aggregate can be large compared to the wavelength. This situation applies to when soot particles formed in flames are measured using methods based on laser light. The method presented in this work, called generalized Rayleigh-Debye-Gans, leads to closed-form expressions for the scattered intensity and the absorbed power of an ensemble of aggregates with random positions and orientations. The expressions ensure a fast and accurate numerical evaluation of the scattering and absorption from ensembles of aggregates. The numerical results are compared with the ones obtained from the T-matrix method and the discrete dipole approximation method.


Intradomain LexA rotation is a prerequisite for DNA binding specificity.
In the absence of DNA damage the LexA protein represses the bacterial SOS system. We performed molecular dynamic simulations of two LexA dimers bound to operators. Our model predicted that rotation of the LexA DNA binding domain, with respect to the dimerised C-terminal domain, is required for selective DNA binding. To confirm the model, double and quadruple cysteine LexA mutants were engineered. Electrophoretic mobility-shift assay and surface plasmon resonance showed that disulfide bond formation between the introduced cysteine residues precluded LexA specific DNA binding due to blocked domain reorientation. Our model could provide the basis for novel drug design.


Optical Properties of Individual Tar Balls in the Free Troposphere.
Tar balls are brown carbonaceous particles that are highly viscous, spherical, amorphous, and light absorbing. They are believed to form in biomass burning smoke plumes during transport in the troposphere. Tar balls are also believed to have a significant impact on the Earth's radiative balance, but due to poorly characterized optical properties, this impact is highly uncertain. Here, we used two nighttime samples to investigate the chemical composition and optical properties of individual tar balls transported in the free troposphere to the Climate Observatory "Ottavio Vittori" on Mt. Cimone, Italy, using multimodal microspectroscopy. In our two samples, tar balls contributed 50% of carbonaceous particles by number. Of those tar balls, 16% were inhomogeneously mixed with other constituents. Using electron energy loss spectroscopy, we retrieved the complex refractive index (RI) for a wavelength range from 200 to 1200 nm for both inhomogeneously and homogeneously mixed tar balls. We found no significant difference in the average RI of inhomogeneously and homogeneously mixed tar balls (1.40-0.03i and 1.36-0.03i at 550 nm, respectively). Furthermore, we estimated the top of the atmosphere radiative forcing using the Santa Barbara DISORT Atmospheric Radiative Transfer model and found that a layer of only tar balls with an optical depth of 0.1 above vegetation would exert a positive radiative forcing ranging from 2.8 W m-2 (on a clear sky day) to 9.5 W m-2 (when clouds are below the aerosol layer). Understanding the optical properties of tar balls can help reduce uncertainties associated with the contribution of biomass-burning aerosol in current climate models.


Neuropraxis secondary to hemorrhage in a traumatic dislocation of the shoulder.
A case of traumatic shoulder dislocation associated with a tear of the subscapular artery is presented. The main clinical feature was a dramatic neurologic loss of the brachial plexus, reversed by exploration, evacuation of hematoma, and ligation of the bleeding vessel. Early surgical decompression to achieve neurologic recovery is emphasized.


Camptothecin-stabilized topoisomerase I-DNA adducts cause premature termination of transcription.
The antitumor agent camptothecin stabilizes type I topoisomerase-DNA complexes. One of the primary cellular responses to camptothecin exposure is rapid cessation of RNA synthesis. Results obtained by using an in vitro transcription system supplemented with eukaryotic topoisomerase I show that this inhibition can be attributed to physical blockage of the RNA polymerase by camptothecin-stabilized topoisomerase I-DNA complexes on the DNA template. The site of premature termination is located 10 base pairs upstream of the topoisomerase I linked nucleotide residue on the coding strand, corresponding closely to the border of the protected area obtained in a micrococcus nuclease footprint of topoisomerase I. The RNA polymerase transcribes unimpeded through complexes attached to the noncoding strand. No inhibitory effect of camptothecin on RNA transcription was observed with human topoisomerase I isolated from a camptothecin-resistant cell line. Taken together, the data suggest that part of the cytotoxicity of camptothecin is mediated through adduct formation on transcribed DNA, resulting in interference with transcriptional elongation.


Preimplantation genetic diagnosis for myotonic dystrophy type 1: detection of crossover between the gene and the linked marker APOC2.
To report two cases of preimplantation genetic diagnosis (PGD) for myotonic dystrophy type I (DM1) where cross-over between the DMPK locus and a linked polymorphic marker APOC2 was detected. Embryos from in vitro fertilisation (IVF) were biopsied at day 3 of development and single blastomeres collected. Diagnosis was performed by duplex or triplex fluorescent-polymerase chain reaction (F-PCR) to amplify DMPK and APOC2 loci, or DMPK with APOC2 and D19S112 polymorphic markers. A total of 22 oocytes were retrieved from the two patients, 20 were inseminated of which 15 fertilized (75%) and were suitable for biopsy on day 3. A diagnosis was obtained for 12 embryos (80%) and was confirmed in all un-transferred embryos. Crossover between DM1 and APOC2 was detected in two embryos from the two different couples. Transfer of two embryos took place in both cases resulting in two pregnancies. Each couple have had a healthy baby. The above cases highlight the importance of using more than one linked polymorphic marker in PGD-PCR protocols and emphasize the danger of using APOC2 as the sole marker to identify the DM1 mutation.


Cercaria-induced histamine release: a factor in the pathogenesis of schistosome dermatitis?
Cercariae, but not schistosomules, of Schistosoma mansoni are capable of activating the release of histamine from rat peritoneal mast cells in vitro. This activation occurs in the absence of serum and does not require adherence to mast cells. The amount of histamine released is proportional to the number of cercariae present. This mast-cell triggering factor from cercariae remains to be characterized biochemically, but may well play a causal role in the "swimmer's itch" associated with primary schistosome exposure.


Robot-assisted thoracoscopic lobectomy for severe incomplete interlober fissure.
An incomplete interlobar fissure makes thoracoscopic lobectomy difficult and is predictive of morbidity after thoracoscopic lobectomy. This report demonstrates the robot-assisted thoracoscopic (RATS) lobectomy technique for patients with severe incomplete interlobar fissures. A fissureless approach was chosen for pulmonary resection. Near-infrared fluorescence imaging with intravenous indocyanine green (ICG) was used to detect the interlobar line after transection of the bronchus, pulmonary artery and vein. Interlobar fissure was identified and divided by robotic staplers. This combined technique using ICG and fissureless lobectomy made RATS lobectomy safe for patients with severe incomplete interlobar fissures.


[Analysing a public health service network's managerial competence].
Analysing the effectiveness of training-action methodology in developing and strengthening the skills required by public health network managerial staff. The study evaluated an educational programme (pre- and post- evaluation being applied within the programme's framework and conditions, without controlled conditions) in which 37 managerial staff from the Talcahuano Health Service Network (forming part of the Public Health Assistance Network) participated in the Managerial Team Training programme, 2007 and 2008, run by the Bío-Bío University's Entrepreneurial Science Faculty in Chile. A skill-based self-evaluation instrument was applied on two different occasions. The results revealed a lack of management skills-based training in network managerial teams and the need for it through training-action methodology which stimulates such needed managerial skills. Acquiring these skills will lead to providing users with a quality service through better management practice in public health establishments.


The effectiveness of low-cost teleconsultation for emergency head computer tomography in patients with suspected stroke.
Teleradiology in an emergency situation can be used to support rapid neurological decision-making when specialists are remote from the hospital concerned. We have developed a low-cost system using a PDA phone as the receiving equipment. The experimental system was based on a notebook PC to send the images and a PDA phone to receive them. We used commercially available toolbar software for transmitting the information through the mobile phone network. A total of 100 images from clinically suspected strokes within the previous 24 hours were transmitted to a neurologist. The mean size of the original picture was 20.9 kByte and the images were compressed by approximately 2:1 before transmission. The mean transmission time was 48 s per image. The diagnosis from the PDA phone image was in complete agreement with the diagnosis from the original image in cases of acute ischaemic stroke, intracerebral haemorrhage, metastasis and in normal scans. However, there was agreement in only 7 of the 8 cases (88%) of subarachnoid haemorrhage. The overall transmission cost was 400 Thai baht per case. The study showed that good accuracy can be achieved with a low-cost system for teleradiology consultation in stroke.


Comparison of modified ultrafast Papanicolaou stain with the standard rapid Papanicolaou stain in cytology of various organs.
Since the first introduction of Papanicolaou (Pap) stain in 1942 there have been many modifications. Of these, the Ultra-Fast Pap stain has become popular. This technique was further modified in India as many of the reagents were not available in our country. Our study was conducted by adapting this modified staining technique which involves the replacement of Gill's hematoxylin with Harris hematoxylin. The aim of our prospective study was to assess the use of the modified Ultra-Fast Pap stain (MUFP) for fine needle aspiration cytology (FNAC) of various organs in comparison with the standard rapid Pap stain. A total of 100 FNAC cases were studied by random sampling. Two smears were prepared for each case and stained by both, the MUFP and the rapid Pap stain. Scores were given and the quality index was calculated, followed by the statistical analysis. The number of cases was as follows: lymph node (43), thyroid (25), breast (23), salivary gland (02), and soft tissues (07). Scores were given on four parameters: Background of smears, overall staining pattern, cell morphology and nuclear staining. Quality index was calculated from the ratio of score achieved to the maximum score possible. Results were analyzed using Mean, Median, Standard Deviation, 't' paired test, 'P' value and M-diff for statistical significance. Correct diagnosis was made in all cases. The quality index of MUFP smears was better compared to the rapid Pap stain in all the organs, and was statistically significant. MUFP smears showed a clear red blood cells background, transparent cytoplasm and crisp nuclear features. MUFP is a reliable and rapid technique for cytology diagnosis.


[The dedicated amateur].
This is the text of an inauguration lecture at Umeå Universitiy (a chair of the history of science and ideas). The lecture is based on a study of magazines like Populär Teknik (Popular Technology), popular science literature, handbooks for mechanical and electrical experimentation, mail-order catalogs etc. from 1920-50, and its theme is that amateurs and hobbyists interested in popular science, technology and "do-it-yourself" have played an important role in modern society. Here we find a world exclusively occupied by boys and men, where it is made a virtue of playing with technological toys, and where mechanical and electrical tinkering becomes a significant part of the construction of masculinity. But the activities of amateurs and hoppyists can also be seen as an important way of self-education where the boy may get in touch with the scientific and technological frontier of the time, and there are many examples (e.g. in early history of radio or personal computers) where amateurs invented and developed new technology. The spirit of amateurs and hobbyists can even contain elements of a modern civic ideal: don't become dependent upon professional experts, don't trust authorities or big business that want to control technology, trust yourself and your knowledge. In short: do it yourself.


[Prostate cancer detection rates: comparison of standard biopsy with prompt rebiopsy and a one-time extended biopsy].
Prostate biopsy is the gold standard for the detection of prostate cancer (PCA). While national and international guidelines recommend the extraction of 10-12 cores at initial biopsy, some authors plead to initially perform more extensive biopsy protocols. We assessed the PCA detection and complication rates of different biopsy schemes. We relied on the data of 425 men who underwent their first prostate biopsy from April 2005 to May 2013. Exclusion criteria consisted of PSA > 20 ng/ml, prior surgery of the prostate, or intake of 5-α-reductase inhibitors. Overall 357 underwent a 10- to 12-core biopsy, while 68 patients underwent 20-core biopsy. In case of a negative biopsy in the 10-12 cohort, rebiopsy was performed within 6 months, while in the 20-core group clinical follow-up determined further course of action. Endpoints of the study were the overall PCA detection rate and the rate of severe complications, which were defined as complications requiring hospital admission. The effect of the respective biopsy scheme on the PCA detection rate was assessed using uni- and multivariable logistic regression analysis. In the subanalysis, the PCA detection rates between the two groups were compared solely in patients with PSA values ≤10 ng/ml. At initial biopsy, the overall PCA detection rate was 50.4% (214/425). In the 10-12 core group, the PCA detection rate at first biopsy was 52.4% (187/357) and rebiopsy detected a further 19 (11.2%) PCA cases, resulting in a cumulative PCA detection rate of 57.7% (206/357). In the 20-core group, the PCA detection rate was 39.7% (27/68). While the different PCA detection rates were not statistically different when the initial biopsies were compared, biopsy scheme reached independent predictor status when the cumulative PCA detection rate of the 10- to 12-core scheme was compared to the 20-core scheme (p=0.01). Comparable results were obtained only when patients with PSA ≤10 ng/ml were considered. The rate of severe complications was statistically higher in the 20-core group (6.1 vs. 2.4%; p=0.01). Our data indicate that an initial 20-core biopsy does not lead to a higher PCA detection rate compared to an initial 10- to 12-core biopsy. Moreover, the cumulative PCA detection rate of a 10- to 12-core biopsy and prompt repeat biopsy was significantly higher compared to a single 20-core biopsy.


Determination of xanthatin by ultra high performance liquid chromatography coupled with triple quadrupole mass spectrometry: application to pharmacokinetic study of xanthatin in rat plasma.
A sensitive, specific and rapid ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method has been established to study pharmacokinetic properties of xanthatin. Xanthatin, a compound which belongs to sesquiterpene lactone group, was determined in rat plasma with psoralen as internal standard. Chromatographic separation was performed on an Agilent Zorbax Eclipse plus C18 column (50 mm × 2.1 mm, 3.5 μm) with gradient elution system at a flow rate of 0.3 mL/min. The mobile phase was composed of methanol and 0.1% formic acid water solution. Analysis was performed under a triple-quadruple tandem mass-spectrometer with an electrospray ionization (ESI) source via the multiple reaction monitoring (MRM) mode to determine xanthatin at [M+H](+)m/z 247.3→m/z 205.2 and that of IS at [M+H](+)m/z 187.1→m/z 143.0 within 5 min. The assay method exhibited good separation of xanthatin from the interference of endogenous substances. The lower limit of quantification (LLOQ) was 1 ng/mL, with a good linearity within the concentration range of 1-5000 ng/mL (r=0.9990). Intra-day and inter-day precision RSD was less than 9.27%; intra-day and inter-day accuracy was 88.48% and 102.25% respectively. The extraction recoveries of xanthatin range from 82.12% to 89.55%, and the extraction RSD was less than 9.01%. The established LC-ESI-MS/MS method is rapid and sensitive, which has been successfully applied to quantify xanthatin in rat plasma for the first time.


Generation of H-2-reactive T cell lines that bear the 5936 idiotype(s).
The present experiments showed 1) that it was possible to produce mouse T cell lines against MHC determinants with a relatively high success rate by stimulation of purified T cells with allogeneic cells in the presence of irradiated syngeneic spleen cells; 2) that these lines could be led to react against selected H-2 specificities; 3) that only T cell lines established from Ig-1b allotype mice contained 5936-Id+ T cells (5936-Idiotypes are defined by an antiserum against B6 anti-CBA IgG produced in rabbit no 5936, which was tolerant to mouse gamma-globulin); and 4) that antigenic determinants coded by IAk genes induce the 5936-Idiotype(s). The latter data are in accordance with the 5936-idiotype characteristics of primary MLC T blasts. All T cell lines contained both specific MLC-responding cells and cytolytic cells. However, studies on the functional capacity of 5936-Id+ T cells from both primary MLC and the T cell lines showed that neither MLC-responding cells nor cytolytic cells directed against H-2Kk, IAk, or H-2Dk were 5936-Id+. Thus, 5936-Id+ T cells may be regulator cells induced by IAk antigens.


Continuing medical education: a needs analysis of anaesthetists.
The continuing medical education (CME) needs of anaesthetists within Australia, New Zealand, Hong Kong, Malaysia and Singapore have been largely unknown. The aim of this study was to undertake a comprehensive survey of the attitude to CME, learning preferences, attitudes and abilities relating to self-paced material, literature and information searching, preferred content and preferred approach to CME of anaesthetists within these countries. A survey tool was developed and refined for ease of use by pilot-testing. The survey was mailed to 3,156 anaesthetists throughout Australia, New Zealand, Hong Kong, Malaysia and Singapore. Three options for data return were offered; postal reply, facsimile and a data entry web-page. There were 1,800 responses, which represented a response rate of 57%. The demographics of the respondents were similar to the overall demographics of Fellows of the Australian and New Zealand College of Anaesthetists. A large majority of respondents (92%) stated that their involvement in CME improved patient care. However, almost half the respondents reported that they have difficulty either in participating in current CME activities (31%) or implementing new knowledge into their workplace (14%). Anaesthetists within this region appear to be motivated by the need to make better decisions based on independent standards of practice. While Australia is a world leader in flexible education, it is still emerging as a discipline. Flexible education may be used to facilitate anaesthetists' participation in CME activities and in implementation of new knowledge in their workplace.


Evaluation of anemia caused by hemorrhoidal bleeding.
Hemorrhoidal bleeding and anemia are two common entities. The purpose of this article is to review the incidence of hemorrhoidal bleeding that causes anemia in a stable population, to describe patients who have hemorrhoidal bleeding that caused anemia, and to define observations regarding the recovery of their anemia. This was a retrospective chart review of patients seen at the Mayo Clinic and Olmsted Community Hospital in Rochester, Minnesota, from 1976 through 1990. Incidence of hemorrhoidal bleeding that caused anemia was found to be 0.5 patients per 100,000 population per year in Olmsted County from 1976 to 1990. The mean age of 43 patients studied was 50 (range, 25-72) years. Twenty-seven patients were male, and 16 were female. Ninety-three percent of these patients had grade 2 or 3 internal hemorrhoidal disease. Six had impaired coagulation. The mean hemoglobin concentration before treatment was 9.4 g/dl (+/- 0.97 SD). Of note was the description of hemorrhoidal bleeding that included blood squirting or clots passing in 84 percent of patients for whom a description was available. It was found that recovery from anemia after definitive treatment with hemorrhoidectomy was rapid, with a mean hemoglobin concentration of 12.3 g/dl after two months, and by six months, the mean hemoglobin concentration was 14.1 g/dl. It is imperative to evaluate other causes of anemia when presented with hemorrhoidal bleeding with anemia. If no other sources are identified, treatment of the hemorrhoid should be undertaken, and a rapid return of hemoglobin concentration can be expected within two months, and all patients should have a normal hemoglobin by six months. Failure to recover hemoglobin concentration should prompt further or repeated evaluation for other causes of bleeding.


[A clinical case of secondary tumor of the penis from the rectum, with malignant priapism].
We report a clinical case of carcinoma of the rectum. A 45-year-old patient had undergone resection of the rectum and proctostomy 22 months ago. Carcinoma caused metastasis to the corpora cavernosa of the penis in this patient, and caused local recurrence of the carcinoma of the rectum, pulmonary metastasis and malignant priapism. A statistical analysis of 62 cases of secondary tumor of the penis in Japan was also made. The present clinical case was the 62nd case of secondary tumor of the penis in Japan, and the 4th case of secondary penile tumor from the rectum. The primary foci of the secondary tumor of the penis are mostly in the urinary bladder and the prostate, followed by the rectum, kidney, pelvis of the kidney and the ureter. Primary sites in the urogenital organs were found in 82.3% and in the neighboring organs in 85.2%. As the route of metastasis of the secondary tumor of the penis, arterial blood, retrovenous, retro-lymph and direct infiltrating metastasis may be possible. Secondary tumor of the penis is mostly found in aged persons, and the major symptoms may be penile nodule and mass, malignant priapism, penile pain and tenderness, and difficulty in urination and retention of urine. Regardless of the length to metastasis and difference in the treatment of the metastatic focus, the secondary tumor of the penis is poor in prognosis, and survival period may be up to 7 months. From the findings of post-mortem examination, secondary tumor of the penis should be regarded as a secondary sign due to recurrence of the primary tumor or presence of metastasis in other organs, and careless surgical operation should be avoided.


Optimization of the Extraction Conditions of Bioactive Compounds from Ocimum basilicum Leaves Using Ultrasound-Assisted Extraction via a Sonotrode.
Sweet basil (Ocimum basilicum) leaves are rich in bioactive compounds that present therapeutic benefits for human health. Ultrasonic-assisted extraction (UAE) is frequently used to obtain phenolic compounds from plants/herbal sources. However, few works have developed multi-variable studies to find the optimal conditions to extract the maximum amount of compounds, especially when applied to UAE via a sonotrode. The purpose of this work was to perform a multi-variable study by employing a Box-Behnken design to collect the highest active compound content from Ocimum basilicum leaves. The efficacy of the design was endorsed by ANOVA. The studied parameters for UAE via a sonotrode were the ethanol/water ratio, amplitude, and time. The analyzed responses were the rosmarinic acid, the sum of phenolic acids, and the sum of phenolic compounds content. The optimal conditions were found to be 50% ethanol/water, 50% amplitude, and 5 min. Twenty bioactive compounds were identified by HPLC-ESI-TOF-MS when the extract was collected by applying the optimal conditions. Ocimum basilicum may be appreciated as a valuable source of important bioactive substances for pharmaceutical use.


From Patients to Policy: Population Intervention Effects in Epidemiology.
Interest in implementation science and recent calls for consequentialist epidemiology urge epidemiologists to produce work more immediately applicable to public health practice. A clear vocabulary for such approaches is lacking. Here, we present a potential taxonomy of causal effects, distinguishing between "exposure effects" more relevant to patients and individuals; and "population intervention effects" more relevant to public health policy. We discuss this range of effects using figures and a simple numerical example.


Spatial Attention Reduces Burstiness in Macaque Visual Cortical Area MST.
Visual attention modulates the firing rate of neurons in many primate cortical areas. In V4, a cortical area in the ventral visual pathway, spatial attention has also been shown to reduce the tendency of neurons to fire closely separated spikes (burstiness). A recent model proposes that a single mechanism accounts for both the firing rate enhancement and the burstiness reduction in V4, but this has not been empirically tested. It is also unclear if the burstiness reduction by spatial attention is found in other visual areas and for other attentional types. We therefore recorded from single neurons in the medial superior temporal area (MST), a key motion-processing area along the dorsal visual pathway, of two rhesus monkeys while they performed a task engaging both spatial and feature-based attention. We show that in MST, spatial attention is associated with a clear reduction in burstiness that is independent of the concurrent enhancement of firing rate. In contrast, feature-based attention enhances firing rate but is not associated with a significant reduction in burstiness. These results establish burstiness reduction as a widespread effect of spatial attention. They also suggest that in contrast to the recently proposed model, the effects of spatial attention on burstiness and firing rate emerge from different mechanisms.


Shifts in grassland invasibility: effects of soil resources, disturbance, composition, and invader size.
There is an emerging recognition that invasibility is not an intrinsic community trait, but is a condition that fluctuates from interactions between environmental forces and residential characters. Elucidating the spatiotemporal complexities of invasion requires inclusion of multiple, ecologically variable factors within communities of differing structure. Water and nutrient amendments, disturbance, and local composition affect grassland invasibility but no study has simultaneously integrated these, despite evidence that they frequently interact. Using a split-plot factorial design, we tested the effects of these factors on the invasibility of C3 pasture communities by smooth pigweed Amaranthus hybridus L., a problematic C4 forb. We sowed seeds and transplanted 3-week old seedlings of A. hybridus into plots containing monocultures and mixtures of varying composition, subjected plots to water, soil disturbance, and synthetic bovine urine (SBU) treatments, and measured A. hybridus emergence, recruitment, and growth rate. Following SBU addition, transplanted seedling growth increased in all plots but differed among legume and nonlegume monocultures and mixtures of these plant types. However, SBU decreased the number and recruitment rate of emerged seedlings because high residential growth reduced light availability. Nutrient pulses can therefore have strong but opposing effects on invasibility, depending on when they coincide with particular life history stages of an invader. Indeed, in SBU-treated plots, small differences in height of transplanted seedlings early on produced large differences in their final biomass. All facilitative effects of small-scale disturbance on invasion success diminished when productivity-promoting factors were present, suggesting that disturbance patch size is important. Precipitation-induced invasion resistance of C3 pastures by a C4 invader was partly supported. In grazed grasslands, these biotic and environmental factors vary across scales and interact in complex ways to affect invasibility, thus a dynamic patch mosaic of differential invasion resistance likely occurs in single fields. We propose that disturbance patch size, grazing intensity, soil resource availability, and resident composition are inextricably linked to grassland invasions and comment on the utility of community attributes as reliable predictors of invasibility. Lastly, we suggest temporal as well as spatial coincidences of multiple invasion facilitators dictate the window of opportunity for invasion.


Organization and quantification of the elements in the intertubular space in the adult jaguar testis (Panthera onca, LINNAEUS, 1758).
The endocrine portion of mammal testicle is represented by Leydig cells which, together with connective cells, leukocytes, blood and lymphatic vessels, form the intertubular space. The arrangement and proportion of these components vary in the different species of mammals and form mechanisms that keep the testosterone level--the main product of the Leydig cell--two to three times higher in the interstitial fluid than in the testicular blood vessels and 40-250 times higher in these than in the peripheral blood. Marked differences are observed among animal species regarding the abundance of Leydig cells, loose connective tissue, development degree and location of the lymphatic vessels and their topographical relationship with seminiferous tubules. In the jaguar about 13% of the testicular parenchyma is occupied by Leydig cells, 8.3% by connective tissue and 0.3% by lymphatic vessels. Although included in standard II, as described in the literature, concerning the arrangement of the intertubular space, the jaguar has grouped lymphatic vessels in the intertubular space instead of isolated ones. In the jaguar the average volume of the Leydig cell was 2386 microm3 and its average nuclear diameter was 7.7 microm. A great quantity of 2.3 microm diameter lipidic drops was observed in the Leydig cell cytoplasm of the jaguar. The Leydig cells in the jaguar occupy an average 0.0036% of the body weight and the average number per gram of testicle was within the range for most mammals: between 20 and 40 million.


Hydrophilic and Cell-Penetrable Pyrrolidinyl Peptide Nucleic Acid via Post-synthetic Modification with Hydrophilic Side Chains.
Peptide nucleic acid (PNA) is a nucleic acid mimic in which the deoxyribose-phosphate was replaced by a peptide-like backbone. The absence of negative charge in the PNA backbone leads to several unique behaviors including a stronger binding and salt independency of the PNA-DNA duplex stability. However, PNA possesses poor aqueous solubility and cannot directly penetrate cell membranes. These are major obstacles that limit in vivo applications of PNA. In previous strategies, the PNA can be conjugated to macromolecular carriers or modified with positively charged side chains such as guanidinium groups to improve the aqueous solubility and cell permeability. In general, a preformed modified PNA monomer was required. In this study, a new approach for post-synthetic modification of PNA backbone with one or more hydrophilic groups was proposed. The PNA used in this study was the conformationally constrained pyrrolidinyl PNA with prolyl-2-aminocyclopentanecarboxylic acid dipeptide backbone (acpcPNA) that shows several advantages over the conventional PNA. The aldehyde modifiers carrying different linkers (alkylene and oligo(ethylene glycol)) and end groups (-OH, -NH2, and guanidinium) were synthesized and attached to the backbone of modified acpcPNA by reductive alkylation. The hybrids between the modified acpcPNAs and DNA exhibited comparable or superior thermal stability with base-pairing specificity similar to those of unmodified acpcPNA. Moreover, the modified apcPNAs also showed the improvement of aqueous solubility (10-20 folds compared to unmodified PNA) and readily penetrate cell membranes without requiring any special delivery agents. This study not only demonstrates the practicality of the proposed post-synthetic modification approach for PNA modification, which could be readily applied to other systems, but also opens up opportunities for using pyrrolidinyl PNA in various applications such as intracellular RNA sensing, specific gene detection, and antisense and antigene therapy.


Improving Quality of Care for SUDS: Where Do We Go From Here?
: Initiation and engagement (IET), a process quality indicator for the treatment for substance use disorders (SUDs), has been associated with better treatment outcomes and has been part of the Healthcare Effectiveness Data and Information Set for over a decade. However, nationally, IET rates tend to be low and not improving. Integration may be a promising way to improve IET and quality of care, as suggested by the findings. To guarantee that integration is a truly effective mechanism for improving patient engagement and quality would likely require providing clinicians and other primary care providers with additional support and training on SUDs and treatment, and ensure that everyone, regardless of demographic characteristics, can equally benefit from these system level changes.


Traction suture for canalicular lacerations.
Maintaining good wound closure in canalicular lacerations is difficult because of the horizontal tension exerted by the orbicularis muscle on the wound. A method of placing a deep medial canthal traction suture through the medial orbital periosteum to aid in maintaining good wound approximation is presented.


A direct route to bis(imido)uranium(V) halides via metathesis of uranium tetrachloride.
Metathesis reactions between uranium tetrachloride and lithium 2,6-diisopropylphenylamide in the presence of 4,4'-dialkyl-2,2'-bipyridyl (R(2)bpy; R = Me, (t)Bu) or triphenylphosphine oxide (tppo) appear to generate bis(imido)uranium(IV) in situ. These extremely reactive complexes abstract chloride from dichloromethane to generate U(NDipp)(2)Cl(R(2)bpy)(2) or U(NDipp)(2)Cl(tppo)(3) (Dipp = 2,6-(i)Pr(2)C(6)H(3)). The preparation of the bromide and iodide analogues U(NDipp)(2)X(R(2)bpy)(2) was achieved by addition of CH(2)X(2) (X = Br, I) to the uranium(IV) solutions. The uranium(V) halides were characterized by X-ray crystallography and found to exhibit linear N-U-N units and short U-N bonds. Electrochemical measurements were made on the chloride bipyridine species, which reacts readily with iodine or ferrocenium to generate bis(imido)uranium(VI) cations.


The rat liver asialoglycoprotein receptor polypeptide must be inserted into a microsome to achieve its active conformation.
Affinity chromatography on galactose-Sepharose has been utilized to demonstrate that rat liver asialoglycoprotein receptor synthesized in vitro in a reticulocyte lysate system is capable of binding carbohydrate ligand only when dog pancreas microsomes are present during translation. Analysis of receptor isolated from tunicamycin-treated rat hepatocytes indicates that glycosylation is not necessary for receptor activity. Genetically engineered receptor derivatives in which the natural membrane anchor is either deleted entirely or replaced with a cleavable signal sequence derived from dog preproinsulin have been used to demonstrate that: (a) inactive receptor made in the absence of membranes does not result from incorrect nucleation of folding around the hydrophobic portion of the polypeptide which is normally buried in the membrane and (b) the carbohydrate-binding domain of the receptor does not need to be tethered to the luminal side of the membrane to fold correctly. These results suggest that factors within the lumen of the microsomes are essential to establish the native conformation of the binding domain.


A sensitive direct ELISA for detection of prostaglandin E2.
In order to improve the indirect ELISA for detection of PGE(2), a modified direct ELISA technique was developed to measure PGE(2) in cell culture supernatants. An evaluation of three types of coating buffer showed that PGE(2) was adsorbed efficiently to the solid phase using the gelatin phosphate buffer. The sensitivity of the assay was increased by employing polyclonal rabbit anti-PGE(2) antibody dilution of 1/100 and 1% skimmed milk as a blocking solution, with the detection limit of 7.8-500 ng/well. The within-run and between-run coefficients of variation (CV) ranges were 3.2-3.7% and 3.4-3.8%, respectively. A linear standard curve was observed over the range of 0.078-5 microg/mL with a coefficient of determination (r(2)) of 0.99. Our results indicated that the developed direct ELISA was sensitive and suitable for a quick determination of PGE(2) levels from cell culture supernatants.


Everything is Infinite: Children's Beliefs About Endless Space, Time, and Number.
How do children form beliefs about the infinity of space, time, and number? We asked whether children held similar beliefs about infinity across domains, and whether beliefs in infinity for domains like space and time might be scaffolded upon numerical knowledge (e.g., knowledge successors within the count list). To test these questions, 112 U.S. children (aged 4;0-7;11) completed an interview regarding their beliefs about infinite space, time, and number. We also measured their knowledge of counting, and other factors that might impact performance on linguistic assessments of infinity belief (e.g., working memory, ability to respond to hypothetical questions). We found that beliefs about infinity were very high across all three domains, suggesting that infinity beliefs may arise early in development for space, time, and number. Second, we found that-across all three domains-children were more likely to believe that it is always possible to add a unit than to believe that the domain is endless. Finally, we found that understanding the rules underlying counting predicted children's belief that it is always possible to add 1 to any number, but did not predict any of the other elements of infinity belief.


Identification of Non-Electrophilic Nrf2 Activators from Approved Drugs.
Oxidative damage can lead to a wide range of diseases. Nrf2 is an important transcription factor that regulates many of the cytoprotective enzymes involved in the oxidative stress response. Therefore, targeting the regulation of Nrf2 activation is one logical and effective strategy to prevent or lower the risk of oxidative stress-related diseases. Until now, most research has focused on electrophilic indirect Nrf2 activators, but the risk of 'off-target' effects may be associated with these activators. To find novel small non-electrophilic modulators of Nrf2, we started from chemical agents derived from a connectivity map (cMap) and identified 22 non-electrophilic potential Nrf2-activating drugs through a drug repositioning tactic. By determining the expression changes of antioxidant genes in MCF7 cells that were treated with the potential Nrf2 activators using quantitative real-time polymerase chain reaction RT-PCR (real-time polymerase chain reaction) (qRT-PCR), astemizole was found to have a greater scale of upregulating antioxidant genes NQO1, HO-1, and GCLM than the positive control d,l-sulforaphane, although the testing concentration was lower than that of the control. Astemizole is a good potential redox regulator and deserves more pharmacodynamic experimentation to test and verify its feasibility for use as an Nrf2 activator.


Thoracic empyema: management with image-guided catheter drainage.
Forty-three patients with thoracic empyema were treated by means of image-guided catheter drainage. In 40 patients, image-guided catheter drainage was the primary treatment method; in three it was used after conventional, surgical chest tube placement failed. Drainage was performed with ultrasound guidance in 30 patients (69.8%), computed tomography in eight (18.6%), and fluoroscopy in five (11.6%). A combination of guidance modalities was used in six patients. Image-guided catheter drainage alone was successful in 31 of 43 patients (72.1%). In three patients (7%), empyemas were initially drained, but a thoracotomy was ultimately required because of a persistent pleural peel. In eight patients (18.6%), the procedure failed, predominantly due to tube clogging, persistent pneumothorax, or progressive development of a pleural peel. In one patient, drainage was successful but he died 10 days later of complications of renal failure. No major complications were encountered. Treatment of these patients requires a thorough understanding of the pathogenesis of pleural space infection, principles of empyema drainage, techniques of abscess drainage under image guidance, and the use of a pleural drainage system.


The Candida glabrata sterol scavenging mechanism, mediated by the ATP-binding cassette transporter Aus1p, is regulated by iron limitation.
During disseminated infection by the opportunistic pathogen Candida glabrata, uptake of sterols such as serum cholesterol may play a significant role during pathogenesis. The ATP-binding cassette transporter Aus1p is thought to function as a sterol importer and in this study, we show that uptake of exogenous sterols occurred under anaerobic conditions in wild-type cells of C. glabrata but not in AUS1-deleted mutant (aus1Δ) cells. In aerobic cultures, growth inhibition by fluconazole was prevented in the presence of serum, and AUS1 expression was upregulated. Uptake of sterol by azole treated cells required the presence of serum, and sterol alone did not reverse FLC inhibition of growth. However, if iron availability in the growth medium was limited by addition of the iron chelators ferrozine or apo-transferrin, growth of wild-type cells, but not aus1Δ cells, was rescued. In a mouse model of disseminated infection, the C. glabrata aus1Δ strain caused a significantly decreased kidney fungal burden than the wild-type strain or a strain in which AUS1 was restored. We conclude that sterol uptake in C. glabrata can occur in iron poor environment of host tissues and thus may contribute to C. glabrata pathogenesis.


Effect of Auricular Acupressure on Uremic Pruritus in Patients Receiving Hemodialysis Treatment: A Randomized Controlled Trial.
Background. Uremic pruritus (UP) is a common symptom in patients undergoing maintenance hemodialysis for end-stage renal disease (ESRD). Objective. To determine the clinical efficacy of auricular acupressure therapy on pruritus in hemodialysis patients and to explore possible underlying mechanisms. Methods. Patients receiving maintenance hemodialysis at a referral medical center were recruited and assigned to intervention (n = 32) and control (n = 30) groups. The intervention group underwent auricular acupressure treatment three times a week for six weeks. Auricular acupressure was not applied to patients in the control group. However, tape without Vaccaria seeds was applied to the same six auricular acupoints as the intervention group. Pruritus scores were assessed using VAS scores, and enzyme-linked immunosorbent assays (ELISA) were used to measure levels of other possible contributory biochemical factors. Results. There was a significant difference in mean VAS scores between the postintervention and control groups during follow-up (3.844 ± 1.687 versus 5.567 ± 2.285, F = 22.32, P < 0.0001). Compared to the control group, serum histamine levels in the postintervention group at the six-week follow-up had decreased significantly (F = 5.01, P = 0.0290). Conclusion. Our findings suggest that auricular acupressure may be a useful treatment in the multidisciplinary management of UP in ESRD patients.


1,2-3-H cholesterol as a tracer in studies of human cholesterol metabolism.
1,2-(3)H-Cholesterol was fed to a subject together with 4-(14)C-cholesterol at a known (3)H/(14)C ratio. The ratio was satisfactorily preserved in cholesterol recovered from plasma, red cells, and bile, and in bile acids of bile. Isotopic fractionation was seen during thin-layer chromatographic isolation of cholesterol. In work with 1,2-(3)H-cholesterol or its metabolites care should be taken to recover chromatographic bands in their entirety.


Kinetic study of thermostable L-threonine dehydrogenase from an archaeon Pyrococcus horikoshii.
In the genome data base of the hyperthermophilic archaeon Pyrococcus horikoshii, an open reading frame with sequence homology to a gene encoding alcohol dehydrogenase was found. It was demonstrated that the encoded enzyme was a thermostable L-threonine dehydrogenase which can oxidize the hydroxy alkyl residue of L-threonine associated with the reduction of NAD+ or NADP+. This enzyme is a member of the zinc-containing L-threonine dehydrogenase family. One enzyme molecule contained one zinc atom, and this metal was considered to contribute to the hyperthermostablility of the enzyme. The reaction of the enzyme proceeded via a sequential mechanism. The Michaelis constants (Km) for L-threonine and NAD+ were 0.013 and 0.010 mM, respectively, and the maximum reaction rate (Vmax) was 1.75 mmol NADH formed/min/mg-protein at 65 degrees C. The Km values for both L-threonine and NADP+ were larger than those for L-threonine and NAD+ with a similar Vmax value. These results indicate that the enzyme has lower affinity to NADP+ than to NAD+, and the binding affinity for L-threonine depends on the coenzymes.


Finite element method as an alternative to study the electronic structure of confined atoms.
The finite element method (FEM) based on a nonregular mesh is used to solve Hartree-Fock and Kohn-Sham equations for three atoms (hydrogen, helium, and beryllium) confined by finite and infinite potentials, defined in terms of piecewise functions or functions with a well-defined first derivative. This approach's reliability is shown when contrasted with Roothaan's approach, which depends on a basis set. Therefore, its exponents must be optimized for each confinement imposed over each atom, which is a monumental task. The comparison between our numerical approach and Roothaan's approach is made by using total and orbitals energies from the Hartree-Fock method, where there are several comparison sources. Regarding the Kohn-Sham method, there are few published data and consequently the results reported here can be used as a benchmark for future comparisons. The way to solve Hartree-Fock or Kohn-Sham equations by the FEM is entirely appropriate to study confined atoms with any form of confinement potential. This article represents a step toward developing a fully numerical quantum chemistry code free of basis sets to obtain the electronic structure of many-electron atoms confined by arbitrary confinement.


Tacrolimus loaded biocompatible lecithin-based microemulsions with improved skin penetration: Structure characterization and in vitro/in vivo performances.
In order to improve skin penetration of tacrolimus we aimed to develop potentially non-irritant, lecithin-based microemulsions containing ethanol, isopropanol and/or propylene glycol as cosurfactants, varying caprylic/capric triglycerides and propylene glycol monocaprylate as oil phase. The influence of excipients on the size of microemulsion region in pseudo-ternary phase diagrams and their ability to form different types of microemulsions was evaluated. The comprehensive physicochemical characterization of microemulsions and the evaluation of their structure was performed, while the localization of tacrolimus in microemulsions was further investigated using electron paramagnetic resonance spectroscopy. Moreover, stability studies proved no change in tacrolimus content during one year of storage at room temperature. In addition, in vivo skin performance indicated no skin irritation potential of blank microemulsions, whereas in vitro release testing using Franz diffusion cells showed superior release rate of tacrolimus from microemulsions (0.98±0.10 and 0.92±0.11μg/cm2/h for two bicontinuous and 1.00±0.24μg/cm2/h for oil-in-water microemulsion) compared to referent Protopic ointment (0.15±0.08μg/cm2/h). Furthermore, ex vivo penetration assessed through porcine ear skin using tape stripping, confirmed superiority of two microemulsions related to the reference, implying developed microemulsions as promising carriers for dermal delivery of tacrolimus.


Equivalent and non-equivalent binding sites for tRNA on aminoacyl-tRNA synthetases.
Complexes between tRNAPhe (yeast), tRNASer (yeast) and tRNATyr (Escherichia coli) and their cognate aminoacyl-tRNA synthetases have been studied by sedimentation velocity runs in an analytical ultracentrifuge. The amount of complex formation was determined by the absorption and the sedimentation coefficients of the fast-moving boundary in the presence of excess tRNA or excess synthetase respectively. The same method has been applied to unspecific combinations of tRNAs and synthetases. Inactive material of tRNA or synthetase does not influence the results. 1. Two moles of tRNAPhe can be bound to one mole of phenylalanyl-tRNA synthetase with a binding constant greater than 10(6) M-1. The binding constants for both tRNAs are very similar; the binding sites are independent of each other. Omission of Mg2+ does not prevent binding. 2. Two moles of tRNASer can be bound to one mole of Seryl-tRNA synthetase; the binding of the first and second tRNA is non-equivalent, K1 greater than 10(6) M-1, K2 is determined to be 1.3 X 10(5) M-1 at pH 7.2. Omission of Mg2+ prevents complex formation. 3. Tyrosyl-tRNA synthetase behaves very similarly to seryl-tRNA synthetase. The binding constant for the weakly bound tRNA is 2.3 X 10(5) M-1 at pH 7.2, and 2.5 X 10(6) M-1 at pH 6.0. No complexes are observed in the absence of Mg2+. 4. Unspecific binding was only obtained with phenylalanyl-tRNA synthetase. It binds tRNASer (yeast), tRNAAla (yeast) and tRNATyr (E. coli) with a binding constant about 100 times lower compared to its cognate tRNA. The binding data are discussed with respect to the tertiary structure of the tRNAs, the subunit structure of the synthetases and the possible physical basis for the non-equivalence of binding sites.


Immunoelectron microscopic identification of human parvovirus B19.
A mildly macerated, hydropic fetus was delivered spontaneously at 25 weeks gestation by a multigravidous black mother. At autopsy, gross and microscopic evidence suggested fetal anemia, and excessive extramedullary erythroblastosis was present generally. Erythroid precursor cells in the pulmonary capillary circulation contained eosinophilic nuclear inclusions consistent with human parvovirus B19 infection. Transmission electron microscopy on osmicated Epon lung sections showed lucent, granular chromatin corresponding to the inclusions. In rare foci only these sections contained paracrystalline arrays of 20-nm virions. In the same cells, similar virions were seen within the cytoplasm, both randomly distributed and in paracrystalline aggregates. Postembedding immunoelectron microscopy, done on formalin-fixed lung embedded in a hydrophilic resin, showed positive labelling over the nuclear inclusions, and also localized the viral capsid antigen to cytoplasmic virion aggregates. The nuclear aggregates suggest that the virus would reach the circulation after cell lysis whereas those in cytoplasm suggest that parvovirus also may be excreted from infected cells before they lyse.


Note: Effects of several thermal glues used on temperature dependent Hall measurements.
The effects of four thermal glues (cry-con, fixogum, RS 503-357, and silicon-high vacuum-grease from Leybold vacuum) on temperature dependent Hall measurements on n-type silicon are tested. All thermal glues yielded the same results (resistivity, mobility, and charge carrier density) between 300 and 190 K. The use of RS 503-357 drastically distorts the expected results below 190 K, probably due to a phase transition and its latent heat, which affects the sample temperature during the phase transition. All the other thermal glues give reproducible results down to 100 K. Below 100 K, the use of cry-con, fixogum, and the silicon-high vacuum-grease from Leybold vacuum yield decreasing mobility and charge carrier density and increasing resistivity, as temperature decreases, but with different magnitudes. This is explained as the thermal properties of each glue start to diverge. Fixogum seems to give the best thermal conductivity, while the silicon-high vacuum grease from Leybold vacuum performs the worst below 100K. Crycon has an intermediate behavior between these two former ones. Cooling speed plays an important role at these low temperatures.


Measurement of Blood Volume in Patients with Heart Failure: Clinical Relevance, Surrogates, Historical Background and Contemporary Methodology.
The development of clinical congestion resulting from volume overload, either by renal fluid retention or redistribution of blood volume from venous reservoirs, is a recurrent scenario in patients with chronic heart failure (HF). As a result, the treatment of congestion, most commonly by initiating aggressive diuretic therapy, is a front-line issue in the management of patients with HF. However, the association of clinical congestion and volume overload with physical signs and symptoms, as well as other surrogates of volume assessment, has limitations in accuracy and, therefore, reliability to direct appropriate interventions. The ability to quantitate intravascular volume and identify the variability in volume profiles among patients with HF can uniquely inform individualized volume management and aid in risk stratification. This tool is provided by contemporary nuclear medicine-based BVA-100 methodology, which uses the well-established indicator-dilution principle and is a requested topic for discussion in this review.


Hysteroscopic or rectally guided, deep-uterine insemination of mares with spermatozoa stored 18 h at either 5 degrees C or 15 degrees C prior to flow-cytometric sorting.
Practical application of sex-selected spermatozoa in the horse industry would be greatly improved by the ability to develop simplified methods for shipping, storing, and inseminating sex-selected spermatozoa. Acceptable pregnancy rates have been achieved using fresh sex-sorted stallion sperm, however many stallion owners are reluctant to send their stallions to the sorter location for collection during the breeding season. Furthermore, the technology would be more applicable if the hysteroscopic insemination technique was not necessary for adequate pregnancy rates. Hysteroscopic insemination requires expensive equipment and specially trained personnel. In the present study, stallion sperm were sex-sorted after being stored at either 5 degrees C or 15 degrees C for 18 h. Twenty million sex-sorted sperm were then inseminated using one of two insemination techniques: the hysteroscopic method or the rectally guided, deep-uterine technique. Results were determined based on 16-day pregnancy status. A first-cycle pregnancy rate of 72% (18/25) was achieved when sperm were shipped at 15 degrees C, sex-sorted, and then inseminated using the hysteroscopic method. With these results, it can be concluded that stallions are not necessary at the sorter location to achieve acceptable fertility with sex-sorted sperm. There was a tendency for more mares to become pregnant when sperm were shipped at 15 degrees C prior to sorting, when compared to shipment at 5 degrees C. Similarly, there was a tendency for more mares to become pregnant when hysteroscopic insemination was utilized, when compared to the rectally guided, deep-uterine technique. These trends suggest that if larger group numbers were available, significant differences between the treatments may be revealed.


[Lactulose plus live binary Bacillus subtilis in the treatment of elders with functional constipation].
To explore the therapeutic efficacy and safety of lactulose plus live binary Bacillus subtilis in elders with functional constipation. A total of 97 elder outpatients or inpatients with functional constipation at our department from September 2011 to April 2012 were divided into 3 groups: lactulose treatment (n = 32), live binary Bacillus subtilis treatment (n = 31) and combined treatment (n = 34). Among them, there were 57 males and 40 females with an average age of (74 ± 6) years old. The course of treatment was 4 weeks in all groups. Then we observed the effective time, therapeutic efficacy, adverse reaction and change of life quality. (1) There were 62.5% (20/32) effective patients in the lactulose treatment group, 41.9% (13/31) in live binary Bacillus subtilis treatment group and 82.4% (28/34) in combined treatment group during 48 hours. Combined treatment group was significantly higher than lactulose treatment group (P < 0.05) and live binary Bacillus subtilis treatment group (P < 0.01). And lactulose treatment group was higher than live binary Bacillus subtilis treatment group (P < 0.05). (2) After 4 weeks, the total effective rates were 68.7% (22/32), 41.9% (13/31)and 94.2% (32/34)respectively. Combined treatment group was significantly higher than lactulose treatment group (P < 0.05) and live binary Bacillus subtilis treatment group (P < 0.01). Meanwhile, lactulose treatment group was superior to live binary Bacillus subtilis treatment group (P < 0.05). (3) After 4 weeks, there was no statistic difference in total adverse reaction rates among 3 groups (P > 0.05). (4) The life quality score of combined treatment group was significantly higher than lactulose treatment group (P < 0.05) and live binary Bacillus subtilis treatment group (P < 0.01) and lactulose treatment group was higher than live binary Bacillus subtilis treatment group (P < 0.05) after a 4-week treatment. The combined regimen of lactulose and live binary Bacillus subtilis is more effective than lactulose or live binary Bacillus subtilis alone. Besides, there is no significant increase in adverse reactions. Thus the combined regimen of lactulose and live binary Bacillus subtilis is an effective and safe therapeutic method for elders with functional constipation.


Satisfaction and adherence with immunosuppressant treatment in renal transplant patients living with a working graft.
The aim of this study was to analyze patient satisfaction and adherence in a sample of renal transplant patients living with a working allograft. An epidemiological cross-sectional multicenter study was carried out with renal recipients who had received a transplant 6-24 months before and were undergoing immunosuppressant therapy (IT). Sociodemographic and clinical variables registered were dosage, allograft functioning, number of medications, health-related quality of life (HRQoL by SF-6D), patients' satisfaction (SAT-Q) and adherence to medication (abnormal levels of immunosuppressant in blood tests [ALIBT] and clinical impression). Relationships between those parameters were contrasted (chi-square test, Spearman correlation coefficient and Mann-Whitney U-test). Multivariate regression models (linear and logistic) were computed to analyze the factors related to patients' satisfaction and adherence to medication, respectively. Data from 206 patients were collected (61.2% males with a mean age of 53.35 years). Nonadherence rates (29.1% and 31.1%) were found according to clinical impression and ALIBT, respectively (chi-square = 31.810, p<0.001). Overall, global patients' satisfaction (74.000 ± 1.251) and HRQoL (0.765 ± 0.011) levels were high. Low-moderate significant associations between satisfaction and adherence to IT and HRQoL were found (p<0.01). Finally, age, vitality, allograft functioning and dosage were correlated with patient satisfaction (R2=0.174; F(1,185)=4.134; p<0.043). Number of medications (odds ratio [OR] = 0.890; 95% confidence interval [95% CI], 0.812-0.975; p=0.012), convenience domain (OR=1.037; 95% CI, 1.005-1.070; p=0.021) and clinical criteria (OR=6.135; 95% CI, 2.945-12.782; p<0.001) were associated with adherence. In renal transplant patients, satisfaction with IT is related to the levels of HRQoL and compliance.


[Comparative antioxidant action on the level of reactive oxygen species in normal and transformed fibroblasts].
We studied the changes in the level of reactive oxygen species (ROS) in normal (3T3) and transformed (3T3-SV40) murine fibroblasts under the antioxidant action for 15 min using fluorescent probe carbo- xy-H2DCFDA. We have shown that N-acetylcysteine (NAC) decreased ROS level in both cellular types. Another antioxidant, alpha-lipoic acid (ALA), and its reduced form, dihydrolipoic acid (DHLA), caused the prooxidant effects. Both ALA and DHLA in the concentration range of 0.1-1.25 mM increased ROS level in dose dependent manner in both cellular types. The ability of ALA and DHLA to activate hydrogen peroxide production is discussed.


Autoimmune gastritis presenting as iron deficiency anemia in childhood.
To characterize clinical, laboratorial, and histological profile of pediatric autoimmune gastritis in the setting of unexplained iron deficiency anemia investigation. A descriptive, observational study including pediatric patients with a diagnosis of autoimmune gastritis (positive parietal cell antibody and gastric corpus atrophy) established in a 6 year period (2006-2011) in the setting of refractory iron deficiency anemia (refractoriness to oral iron therapy for at least 6 mo and requirement for intravenous iron therapy) investigation, after exclusion of other potentially contributing causes of anemia. Helicobacter pylori (H. pylori) infection and anti-secretory therapy were also excluded. Data were retrospectively collected from clinical files, including: demographic data (age, gender, and ethnic background), past medical history, gastrointestinal symptoms, familial history, laboratorial evaluation (Hb, serum ferritin, serum gastrin, pepsinogen I/ pepsinogen II, B12 vitamin, intrinsic factor autoantibodies, thyroid autoantibodies, and anti-transglutaminase antibodies), and endoscopic and histological findings (HE, Periodic Acid-Schiff/Alcian blue, gastrin, chromogranin A and immunochemistry analysis for CD3, CD20 and CD68). Descriptive statistical analysis was performed (mean, median, and standard deviation). We report a case-series concerning 3 girls and 2 boys with a mean age of 13.6 ± 2.8 years (3 Caucasian and 2 African). One girl had type I diabetes. Familial history was positive in 4/5 cases, respectively for autoimmune thyroiditis (2/5), sarcoidosis (1/5) and multiple myeloma (1/5). Laboratorial evaluation on admission included: Hb: 9.5 ± 0.7 g/dL; serum ferritin: 4.0 ± 0.9 ng/mL; serum gastrin: 393 ± 286 pg/mL; low pepsinogen I/ pepsinogen II ratio in 1/5 patients; normal vitamin B12 levels (analyzed in 3 patients). Endoscopy findings included: duodenal nodularity (2/5) and gastric fold softening (2/5), and histological evaluation showed corpus atrophic gastritis with lymphocytic infiltration (5/5), patchy oxyntic gland mononuclear cell infiltration (5/5), intestinal and/or pseudo-pyloric metaplasia in corpus mucosa (4/5), and enterochromaffin cell hyperplasia (4/5). Immunochemistry for gastrin on corpus biopsies was negative in all cases. Duodenal histology was normal. All biopsies were negative for H. pylori (Giemsa staining and cultural examination). We highlight autoimmune gastritis as a diagnosis to be considered when investigating refractory iron deficiency anemia in children, particularly in the setting of a personal/familial history of autoimmune disease, as well as the diagnostic contribution of a careful immunohistological evaluation.


[A case of chemotherapy by the transarterial catheter with reservoir against malignant lymphoma of the colon].
We had a case of malignant lymphoma of the colon with two lesions, one in the transverse colon and the other in the ascending colon. The tumor of the transverse colon was resected, but that of the ascending colon was unresectable. Chemotherapy was performed through the catheter with reservoir via the iliac artery into the right colic artery. Three months later, the tumor disappeared completely, and the ascending colon was resected. On histopathological examination, there was no lymphoma cell in the ascending colon. Chemotherapy by a transarterial catheter with reservoir is a new method of treatment against malignant lymphoma.


Co-aggregation of laccase and nature egg white: a simple method to prepare stable and recyclable biocatalyst.
Cross-linked enzyme aggregates (CLEAs) are a versatile and effective method for enzyme immobilization, which is exquisitely simple and amenable to rapid optimization. In this study, nature egg white, which is low cost, easily available, and nontoxic, was used as protein feeder to replace traditional protein feeder (bovine serum albumin, etc.) in the preparation of laccase CLEAs (CLEAs-egg). The effects of the various parameters--nature of the precipitant, temperature, glutaraldehyde concentration, and cross-linking time--on the activity recovery of the resulting CLEAs were studied. The laccase CLEAs-egg exhibited increased stability compared to the free and the laccase CLEAs without protein feeder. The thermal stability of CLEAs-egg was improved and showed 1.3- and 1.8-fold increase in activity at 40 and 60 °C after 5 h incubation, respectively. The stability of CLEAs-egg against denaturants (urea and GndHCl) and protease (trypsin) was also improved. Laccase CLEAs-egg was also demonstrated to be an active and stable biocatalyst in the removal of chlorophenol. After 30 h, 83.6 and 91.5% of 4-chlorophenol and 2,4-dichlorophenol can be removed.


Warfarin dosage requirements: prospective clinical trial of a method for prediction from the response to a single dose.
We have previously described a model for predicting individual daily maintenance dosage (MD) requirements of warfarin 24 h after the administration of a single dose. This model relies on measurement of the initial anticoagulant response as the 24 h percentage fall in plasma clotting factor VII activity. It permits prediction of the individual MD given the size of the initial dose, a baseline and desired maintenance value of the prothrombin ratio, and a baseline and 24 h plasma level of factor VII activity. We now present the results of a prospective clinical trial of the method. Data from 65 patients were suitable for analysis. The mean daily MD of warfarin was 4.0 mg (range 1-10 mg). There was a moderately strong linear relationship between predicted and actual MDs of warfarin (r = 0.66, P less than 0.001). Actual vs predicted MDs in individual patients were not significantly different. The mean difference was 0.39 mg. The results of this prospective trial suggest that our model predicts warfarin MD requirements with reasonable accuracy. Nevertheless, the accuracy of the model is not sufficient to replace careful clinical and haematological monitoring of each patient commencing warfarin therapy.


An illustration of the experimental range of variation of blood pressure.
The nominal uniformity of long-term mean pressure (approximately 100 mmHg at heart level) for all mammalian species belies the broad nature of its variance, which is found at many time scales. Such variations should be a useful index of physiologically normal and pathological processes. However, it is dubious whether a scientifically meaningful determination of central blood pressure at its many process scales can be achieved from a few isolated measurements: to cite a common and highly significant instance, measurement made by a physician on a patient during one or two office visits. The data presented here are far from exhaustive (a few reports in the literature and detailed longitudinal data on 1 subj), but they serve to illustrate a protocol and a sample of the physiological results that might be expected if data were gathered for larger populations. The basic scales of interest lie in the lower-frequency domain, involving periods of fluctuations longer than tens of minutes.


Six-year follow up of atraumatic restorative treatment restorations placed in Chinese school children.
This study aimed to evaluate the clinical performance of atraumatic restorative treatment (ART) restorations placed in school children in China over a 6-year period. This study was implemented in 1996 and 294 ART restorations were placed in 197 children aged 12-13 years by five assistant dentists in four schools. Standard ART procedures and instruments were used combined with a high-strength glass-ionomer restorative material. One examiner evaluated the restorations annually using the ART criteria while at 5 years an independent external examiner used US Public Health Service (USPHS) criteria. Fifty-eight per cent of the restorations were followed for 6 years. At the 6-year evaluation examination, 76% and 59% of the small and large restorations respectively were present and were without major wear or defect (P < 0.01). Similar results were obtained when using the USPHS criteria. Results of a multilevel survival analysis show that the correlation between restoration failure and operator was small but failure of restorations placed in the same child was substantial. Net wear of the small and large restorations after 6 years were 176 and 172 microm respectively (P > 0.05). The 6-year survival rate of the class I ART restorations in this study, especially the smaller ones, was satisfactory. This suggests that the ART approach can be used in the school setting to improve the oral health of large populations of underserved children.


Brain circuitry, behavior, and cognition: A randomized placebo-controlled trial of donepezil in fragile X syndrome.
Fragile X syndrome, the most common inherited cause for intellectual disability, is associated with alterations in cholinergic among other neurotransmitter systems. This study investigated the effects of donepezil hydrochloride, a cholinesterase inhibitor that has potential to correct aberrant cholinergic signaling. Forty-two individuals with fragile X syndrome (mean age=19.61 years) were randomized to receive 2.5-10.0 mg of donepezil (n=20, seven females) or placebo (n=22, eight females) per day. One individual in the active group withdrew at week 7. Outcomes included the contingency naming test, the aberrant behavior checklist, and behavior and brain activation patterns during a functional magnetic resonance imaging gaze discrimination task. There were no significant differences between active and placebo groups on cognitive (contingency naming task) or behavioral (total score or subscales of the aberrant behavior checklist) outcomes. At baseline, the active and placebo groups did not differ in functional magnetic resonance imaging activation patterns during the gaze task. After 12 weeks of treatment the active group displayed reduced activation in response to the averted vs direct gaze contrast, relative to the placebo group, in the left superior frontal gyrus. Reduced functional brain activation for the active group may represent less arousal in response to direct eye gaze, relative to the placebo group. Change in functional magnetic resonance imaging activation patterns may serve as a more sensitive metric and predictor of response to treatment when compared to cognitive and behavioral assessments. Our results suggest that donepezil may have an impact on brain functioning, but longer term follow-up and concomitant behavioral intervention may be required to demonstrate improvement in cognition and behavior.