Herpes simplex neuropathy.
Atypical facial pain and permanent sensory loss in the second and third divisions of the trigeminal nerve developed in a patient who had had multiple attacks of herpes simplex neuralgia over a period of 8 years. Intravenous cytosine arabinoside failed to prevent a recurrence of the vasicular eruption, but carbamazepine produced symtomatic pain relief. This case demonstrates that herpes simplex can closely mimic herpes zoster as a cause of postherpetic neuralgia and suggests a possible etiology of atypical facial pain and/or trigeminal sensory neuropaty in some patients.


A hip wear simulator with 100 test stations.
A novel high-capacity hip wear simulator of the pin-on-disc type was designed, built, and validated. This so-called Super-CTPOD (circularly translating pin-on-disc) device has as many as 100 separate test stations, being an advanced version of the previously validated 12-station CTPOD. A validity test was done so that in all stations the specimens and the test conditions were as similar as possible. Hence, for the first time in this field, an adequate number of similar tests was done for a proper statistical analysis of wear data. The pins were conventional, gamma-sterilized ultra-high molecular weight polyethylene, and the discs were polished CoCr. The lubricant was diluted calf serum and the test length 3 million cycles. In the course of the test, the pins became highly polished, whereas the discs remained practically unchanged. The majority of the polyethylene wear particles were rounded, with a mean diameter of 0.25 microm. The 100 wear factor values computed from the 100 steady state wear rate values of the pins were normally distributed, the mean +/- 95 per cent confidence interval being 1.63 +/- 0.017 x 10(-6) mm3 /N m. The standard deviation was 5.4 per cent of the mean. There were no outliers. The wear mechanisms and the wear factor agreed well with clinical findings. Altogether, the Super-CTPOD test system was shown to be a unique combination of validity, low variation, capacity, efficiency, reliability, productivity, economy, ease of operation, and compact size.


Association of ankylosing spondylitis, Crohn's disease and Takayasu's arteritis in a child.
The authors report the case of a 15-year-old, HLA-B27-positive male patient who presented a rare association of ankylosing spondylitis, Crohn's disease and Takayasu's arteritis, which resulted in death. A brief review of the literature is provided.


[Prevalence of white-coat hypertension and masked hypertension in the general population, through home blood pressure measurement].
To determine the prevalence of white-coat hypertension (WCH) and masked hypertension (MH) in the general population, by means of home blood pressure measurement (HBPM). Cross-sectional, descriptive study. Four primary care centres. A sample of 1400 individuals over 18 years old, selected from the Municipal Register of Inhabitants (Huelva, Spain) and randomised and stratified by age and gender. Two blood pressure (BP) measurements in clinic (CBP) and 12 measurements in a week of BP by HBPM were performed (OMRON 705-CP). Pressure was seen as normal when CBP means were <140/90 mm Hg and HBPM was <135/85 mm Hg. WCH was defined as when CBP was >140/90 mm Hg and HBPM <135/85 mm Hg, and hypertension when CBP was >140 mm Hg and HBPM >135/85 mm Hg or patients were in treatment for hypertension. MH was when CBP was <140/90 mm Hg and at home was >135 mm Hg and/or 85 mm Hg. A total of 1153 individuals (82.35% of the sample) with mean age of 45.4 (SD, 16.1) were included: 560 men and 593 women. The prevalence of MH was 8.9% (CI+/-1.6) in the general population and 9.8% (CI+/-3.2) in individuals with hypertension. WCH prevalence was 3.6% (CI+/-1.05) overall and 12.8% (CI+/-3.6) in hypertense patients, with its prevalence increasing steadily as age groups rose (P = .001). The prevalence of WCH in the general population is low, whereas the prevalence of MH is high.


An overview of recent developments in the management and research of trauma.
Trauma is one of the devastating problems of modern society. Each year, more than one million people die of trauma worldwide. In this paper, some of the recent developments in the management and research of trauma are presented: (1) Traumatology and injury epidemiology; (2) Trauma scoring and multiple injuries; (3) Blast injury and impact injury; (4) Mine injuries and firearm injury; (5) Classification of war wounds; and (6) Basic science research on trauma.


Evaluating the risk for Usutu virus circulation in Europe: comparison of environmental niche models and epidemiological models.
Usutu virus (USUV) is a mosquito-borne flavivirus, reported in many countries of Africa and Europe, with an increasing spatial distribution and host range. Recent outbreaks leading to regional declines of European common blackbird (Turdus merula) populations and a rising number of human cases emphasize the need for increased awareness and spatial risk assessment. Modelling approaches in ecology and epidemiology differ substantially in their algorithms, potentially resulting in diverging model outputs. Therefore, we implemented a parallel approach incorporating two commonly applied modelling techniques: (1) Maxent, a correlation-based environmental niche model and (2) a mechanistic epidemiological susceptible-exposed-infected-removed (SEIR) model. Across Europe, surveillance data of USUV-positive birds from 2003 to 2016 was acquired to train the environmental niche model and to serve as test cases for the SEIR model. The SEIR model is mainly driven by daily mean temperature and calculates the basic reproduction number R0. The environmental niche model was run with long-term bio-climatic variables derived from the same source in order to estimate climatic suitability. Large areas across Europe are currently suitable for USUV transmission. Both models show patterns of high risk for USUV in parts of France, in the Pannonian Basin as well as northern Italy. The environmental niche model depicts the current situation better, but with USUV still being in an invasive stage there is a chance for under-estimation of risk. Areas where transmission occurred are mostly predicted correctly by the SEIR model, but it mostly fails to resolve the temporal dynamics of USUV events. High R0 values predicted by the SEIR model in areas without evidence for real-life transmission suggest that it may tend towards over-estimation of risk. The results from our parallel-model approach highlight that relying on a single model for assessing vector-borne disease risk may lead to incomplete conclusions. Utilizing different modelling approaches is thus crucial for risk-assessment of under-studied emerging pathogens like USUV.


Longitudinal trends in aphasia in the United States.
Few studies have used national data to characterize the occurrence of aphasia in the U.S. The purpose of this project was to use national hospital discharge data to examine the number and characteristics of patients discharged from U.S. hospitals with a diagnosis of aphasia. We examined data from the National Inpatient Sample (NIS) (1997-2006) using ICD-9 codes for aphasia to identify the number and demographic characteristics of patients with aphasia. Between 1997 and 2006 the number of individuals with aphasia was approximately 100,000 per year. During the 10-year period, the majority of individuals with aphasia were 65 years of age and older, female, had Medicare as a primary payer source and resided in the South. The occurrence of aphasia and demographic characteristics of individuals with aphasia has been generally consistent in the U.S. from 1997 to 2006. Future studies are needed to quantify direct and indirect costs of treating individuals with aphasia as well as other factors that determine the true impact of aphasia and other neurologically based disorders of communication.


Colocalization of glial fibrillary acidic protein, metallothionein, and MHC II in human, rat, NOD/SCID, and nude mouse skin keratinocytes and fibroblasts.
The expression of glial fibrillary acidic protein (GFAP) by perivascular cells of many mammalian organs suggests an as yet unknown function of this intermediate filament protein in the maintenance of homeostasis and vascular permeability at the blood-tissue interface. Although a similar situation may exist at the air-tissue interface, the cellular distribution of GFAP in skin tissue has never been demonstrated. To approach this issue, we have employed immunofluorescence and Western blotting techniques to detect GFAP in skin sections of young and adult humans, normal rodents, and two types of mutant mice, as well as in rat lung sections, and in cultured human keratinocytes and fibroblasts. Colocalization with antigens known to be associated with GFAP in other tissues was also tested. Epidermal and hair follicle keratinocytes and dermal fibroblasts showed distinct staining for GFAP as well as colocalization with alpha-actin, metallothionein, and antigens of the class-II major histocompatibility complex (MHC II). GFAP was also identified in rat alveolar fibroblasts which, in common with keratinocytes, form part of the air-tissue interface. GFAP was upregulated together with MHC II in nude mice but was barely detectable in the skin of non-obese diabetic severe combined immunodeficiency mice, suggesting a possible involvement in antigen-presenting functions. The intriguing distribution of a common set of antigens both in certain cells of the integumentary system and at the blood-tissue interfaces of internal organs suggests the involvement of these proteins in universal mechanisms controlling tissue homeostasis and protection.


A heterozygous mutation in GOT1 is associated with familial macro-aspartate aminotransferase.
Macro-aspartate aminotransferase (macro-AST) manifests as a persistent elevation of AST levels, because of association of the protein with immunoglobulins in the circulation. Macro-AST is a rare, benign condition without a previously confirmed genetic basis. Whole exome sequencing (WES)-based screening was performed on 32 participants with suspected familial macro-AST, while validation of variants was performed on an extended cohort of 92 probands and 1,644 healthy controls using Taqman genotyping. A missense variant (p.Gln208Glu, rs374966349) in glutamate oxaloacetate transaminase 1 (GOT1) was found, as a putative causal variant predisposing to familial macro-AST. The GOT1 p.Gln208Glu mutation was detected in 50 (54.3%) of 92 probands from 20 of 29 (69%) families, while its prevalence in healthy controls was only 0.18%. In silico analysis demonstrated that the amino acid at this position is not conserved among different species and that, functionally, a negatively charged glutamate on the GOT1 surface could strongly anchor serum immunoglobulins. Our data highlight that testing for the p.Gln208Glu genetic variant may be useful in diagnosis of macro-AST. Higher than normal levels of aspartate aminotransferase (AST) in the bloodstream may be a sign of a health problem. Individuals with macro-AST have elevated blood AST levels, without ongoing disease and often undergo unnecessary medical tests before the diagnosis of macro-AST is established. We found a genetic variant in the GOT1 gene associated with macro-AST. Genetic testing for this variant may aid diagnosis of macro-AST.


Age-related changes in the latency of the visual evoked potential: influence of check size.
Pattern reversal visual evoked potentials were recorded from visually normal adults between 10 and 80 years of age. Two check sizes, 12 and 48 min, were used. The results showed that the latency of the first major positive component, P1, increased with age for both check sizes. This rate of increase was nearly twice as fast for 12 min checks. This difference is most likely a reflection of the differential effects of aging processes on the various spatial frequency channels in the human visual system.


Modulation of the immune response by antigen-reactive lymphocytes after cultivation with gangliosides.
GM1 ganglioside isolated from mouse brain was found to be capable of inhibiting the thymocytotoxicity of AKR anti-Thy 1.2 antiserum and to a lesser extent anti-BAtheta antiserum. GD1b ganglioside of mouse brain and thymocytes inhibited the thymocytotoxicity of rabbit anti-BAtheta anti-serum for mouse thymocytes. When GM1 ganglioside, in the form of cholesterol-lecithin liposomes, was incubated with spleen cell cultures in the presence of SRBC, depressed anti-SRBC hemolytic plaque responses were observed. This effect could be neutralized by first absorbing the GM1 liposomes with anti-Thy-1.2 antibodies. The kinetics of GM1 numbers when the ganglioside was added even as late as the 4th day of culture. Results of experiments in which GM1 ganglioside was incubated with either bone marrow cells or with thymocytes suggest that the target cell for GM1 liposomes is the B lymphocytes.


Toxic-therapeutic ratio of sodium cyanate.
Six patients with sickle cell anemia were treated with sodium cyanate (30 mg/kg/day). In four, treatment was stopped because of definite or suspected toxicity, and no improvement was seen in the other two. Most alarming was the sudden development of peripheral motor neuropathy in a patient whose red blood cells contained less than 0.6 mols NCO-/mol of hemoglobin: six months after treatment was stopped, function had not completely returned in this patient. Safe oral dosage regimens may not be effective, but extra-corporeal treatment of sickle cells with cyanate, or other compounds, might circumvent that problem.


Peripheral airways mucus clearance in stable asthma is improved by oral corticosteroid therapy.
Inhaled 99mTc-labelled particles have been used to assess mucus clearance from peripheral, intermediate and inner lung zones of 12 patients with stable asthma. The method of analysis relies on a ventilation image with 81mKr to estimate the distribution of radioaerosol alveolar deposition so that clearance from each zone can be related just to particles deposited in the ciliated conducting airways. In calculating clearance from intermediate and inner lung zones, allowance is made for particles transported into these zones from more distal regions of the lung. Peripheral zone clearance in the asthmatic subjects improved significantly (p less than 0.01) after four weeks of corticosteroid treatment (two weeks on 15 mg prednisolone orally each day, plus two weeks on 30 mg). No significant change occurred in clearance from the inner zone when all patients were considered together. However, the six patients who prior to treatment coughed relatively infrequently did show a significant (p less than 0.05) increase in clearance from the inner zone as well as from the peripheral zone.


Interfacial Shear Strength and Adhesive Behavior of Silk Ionomer Surfaces.
The interfacial shear strength between different layers in multilayered structures of layer-by-layer (LbL) microcapsules is a crucial mechanical property to ensure their robustness. In this work, we investigated the interfacial shear strength of modified silk fibroin ionomers utilized in LbL shells, an ionic-cationic pair with complementary ionic pairing, (SF)-poly-l-glutamic acid (Glu) and SF-poly-l-lysine (Lys), and a complementary pair with partially screened Coulombic interactions due to the presence of poly(ethylene glycol) (PEG) segments and SF-Glu/SF-Lys[PEG] pair. Shearing and adhesive behavior between these silk ionomer surfaces in the swollen state were probed at different spatial scales and pressure ranges by using functionalized atomic force microscopy (AFM) tips as well as functionalized colloidal probes. The results show that both approaches were consistent in analyzing the interfacial shear strength of LbL silk ionomers at different spatial scales from a nanoscale to a fraction of a micron. Surprisingly, the interfacial shear strength between SF-Glu and SF-Lys[PEG] pair with partially screened ionic pairing was greater than the interfacial shear strength of the SF-Glu and SF-Lys pair with a high density of complementary ionic groups. The difference in interfacial shear strength and adhesive strength is suggested to be predominantly facilitated by the interlayer hydrogen bonding of complementary amino acids and overlap of highly swollen PEG segments.


[Plasmapheresis treatment in 2 children with SSPE (subacute sclerosing panencephalitis). Various considerations on symptomatology, pathophysiology and therapy].
Subacute sclerosing panencephalitis is a rare slowly progressive neurodegenerative disease in children and young adults. The course of the disease is 'typically' progressive until a vegetative state and death. Otherwise, the course might be 'atypical', with periods of relative stability or even some improvement. We describe two patients one of whom showed the typical course of the disease, whereas the other one showed the atypical form. Both patients were treated with plasmapheresis without noticeable favorable effects. The clinical symptomatology, the pathogenesis and the various therapeutical approaches are discussed.


Mechanical Mitral Valve Replacement during the 2nd Trimester of Pregnancy.
We report the case of a 44-year-old pregnant woman who was diagnosed with symptomatic severe mitral stenosis that did not respond to optimal medical therapy and balloon valvuloplasty. After a multidisciplinary team discussion on the timing and risks of interventions and postoperative optimization of peripartum anticoagulation, the patient underwent mechanical mitral valve replacement during the 2nd trimester of pregnancy. The outcome was excellent for the mother and the infant. This case emphasizes the importance of a multidisciplinary approach in managing unusual cases.


Retinoic Acid Facilitates Toll-Like Receptor 4 Expression to Improve Intestinal Barrier Function through Retinoic Acid Receptor Beta.
Vitamin A (VA) protects the intestinal epithelial barrier by improving cell migration and proliferation. Our previous studies demonstrated that VA deficiency (VAD) during pregnancy suppresses the systemic and mucosal immune responses in the intestines of offspring and that VA supplementation (VAS) during early life can increase immune cell counts. However, little is known about the mechanisms by which VA regulates intestinal epithelial barrier function. Caco-2 cells were treated with all-trans retinoic acid (ATRA) for 24 hours to determine the optimum ATRA concentration to which the cells in question respond. Caco-2 cells were infected with recombinant adenoviruses carrying retinoic acid receptor beta (Ad-RARβ) and small interfering RARβ(siRARβ) to assess the effects of RARβ signalling on the expression of specific proteins. A siTLR4 lentivirus was used to knockdown Toll-like receptor 4 (TLR4) in Caco-2 cells to determine its role in the protective effects of VA on the intestinal epithelial barrier, and experiments involving TLR4-knock-out mice were performed to verify the effect of TLR4. VA normal (VAN), VAD and VAS rat models were established to confirm that changes in RARβ, TLR4 and ZO-2 expression levels that occurred following decreases or increases in retinol concentrations in vivo, and the permeability of the Caco-2 cell monolayer, as well as that of the epithelial barrier of the rat intestine was detected by measuring transepithelial resistance (TER) or performing enzyme-linked immunosorbent assay (ELISA). Retinoic acid receptor (RAR), toll like receptor (TLR) and tight junction (TJ) mRNA and protein expression levels in Caco-2 cells and the colon monolayers in the rat and mouse models were measured by PCR and western blotting, respectively. Co-immunoprecipitation (co-IP) and immunofluorescence staining were performed to assess the interactions among RARβ, TLR4 and zonula occluden-2 (ZO-2) in Caco-2 cells, and chromatin immunoprecipitation (ChIP) assay was performed to assess the binding between RARβ and the TLR4 promoter sequence in Caco-2 cells. In the present study, ATRA treatment not only increased the TER of the Caco-2 monolayer but also up-regulated the expression levels of RARβ, TLR4 and ZO-2 in Caco-2 cells. The expression levels of these three proteins were significantly decreased in the colonic epithelial monolayers of VAD rats compared with those of VAN rats and were significantly increased following VAS in the corresponding group compared with the control group. Furthermore, the above changes in TLR4 and ZO-2 expression levels were augmented or attenuated by Ad-RARβ or siRARβ infection, respectively, in Caco-2 cells. Interestingly, siTLR4 down-regulated ZO-2 expression but did not affect RARβ expression in Caco-2 cells, and in VAD mice the lack of TLR4 did not affect ZO-2 expression. We noted direct interactions between RARβ and TLR4, TLR4 and ZO-2 in Caco-2 cells, and ChIP assay showed that RARβ could bind to the TLR4 promoter but not the ZO-2 promoter in Caco-2 cells. Taken together, our results indicate that RARβ enhanced ZO-2 expression by regulating TLR4 to improve intestinal epithelial barrier function in Caco-2 cells, as well as in rat and mouse models, but not in humans.


Effects of piperidine and piperideine alkaloids from the venom of red imported fire ants, Solenopsis invicta Buren, on Pythium ultimum Trow growth in vitro and the application of piperideine alkaloids to control cucumber damping-off in the greenhouse.
Pythium ultimum is a plant pathogen that causes significant yield losses on many economically important crops. Chemical treatment has been used for disease control. In searching for alternatives, venom piperidine and piperideine alkaloids from red imported fire ants were tested against P. ultimum in vitro, and piperideines were employed to control cucumber damping-off in the greenhouse as drench treatments. Results Piperidine and piperideine alkaloids of the red imported fire ant significantly inhibited mycelium growth of P. ultimum. Piperidine alkaloids were stable at both room and elevated temperatures. The inhibitory activity positively correlated with the concentrations of piperidine alkaloids in the medium, and the EC(50) = 17.0 µg ml(-1). Germination of sporangia of P. ultimum was negatively correlated with the concentrations of piperidine alkaloids in the medium, and the EC(50) = 12.3 µg ml(-1). The piperideine alkaloid drenching treatment significantly improved seedling emergence and seedling height of cucumber. This is the first report describing the use of venom alkaloids from the red imported fire ant to inhibit P. ultimum in the laboratory and the application of piperideine alkaloids to control damping-off disease caused by P. ultimum in the greenhouse. These findings may lead to the development of a new group of fungicides.


Correlations between changes in conformational dynamics and physical stability in a mutant IgG1 mAb engineered for extended serum half-life.
This study compares the local conformational dynamics and physical stability of an IgG1 mAb (mAb-A) with its corresponding YTE (M255Y/S257T/T259E) mutant (mAb-E), which was engineered for extended half-life in vivo. Structural dynamics was measured using hydrogen/deuterium (H/D) exchange mass spectrometry while protein stability was measured with differential scanning calorimetry (DSC) and size exclusion chromatography (SEC). The YTE mutation induced differences in H/D exchange kinetics at both pH 6.0 and 7.4. Segments covering the YTE mutation sites and the FcRn binding epitopes showed either subtle or no observable differences in local flexibility. Surprisingly, several adjacent segments in the CH2 and distant segments in the VH, CH1, and VL domains had significantly increased flexibility in the YTE mutant. Most notable among the observed differences is increased flexibility of the 244-254 segment of the CH2 domain, where increased flexibility has been shown previously to correlate with decreased conformational stability and increased aggregation propensity in other IgG1 mAbs (e.g., presence of destabilizing additives as well as upon de-glycosylation or methionine oxidation). DSC analysis showed decreases in both thermal onset (Tonset) and unfolding (Tm1) temperatures of 7°C and 6.7°C, respectively, for the CH2 domain of the YTE mutant. In addition, mAb-E aggregated faster than mAb-A under accelerated stability conditions as measured by SEC analysis. Hence, the relatively lower physical stability of the YTE mutant correlates with increased local flexibility of the 244-254 segment, providing a site-directed mutant example that this segment of the CH2 domain is an aggregation hot spot in IgG1 mAbs.


First global transcriptome analysis of brown algae Macrocystis integrifolia (Phaeophyceae) under marine intertidal conditions.
To understand the physiological responses of the brown macroalga Macrocystis integrifolia during the marine tidal cycle, two RNA libraries were prepared from algal frond samples collected in the intertidal zone (0 m depth) and subtidal zone (10 m depth). Samples collected from intertidal zone during low tide was considered as abiotic stressed (MI0), while samples collected from subtidal zone was considered as control (MI10). Both RNA libraries were sequenced on Illumina NextSeq 500 which generated approx. 46.9 million and 47.7 million raw paired-end reads for MI0 and MI10, respectively. Among the representative transcripts (RTs), a total of 16,398 RTs (39.20%) from MI0 and 21,646 RTs (39.24%) from MI10 were successfully annotated. A total of 535 unigenes (271 upregulated and 264 downregulated) showed significantly altered expression between MI0 and MI10. In abiotic-stressed condition (MI0), the relative expression levels of genes associated with antioxidant defenses (vanadium-dependent bromoperoxidase, glutathione S-transferase, lipoxygenase, serine/threonine-protein kinase, aspartate Aminotransferase, HSPs), water transport (aquaporin), photosynthesis (light-harvesting complex) protein were significantly upregulated, while in control condition (MI10) most of the genes predominantly involved in energy metabolism (NADH-ubiquinone oxidoreductase/NADH dehydrogenase, NAD(P)H-Nitrate reductase, long-chain acyl-CoA synthetase, udp-n-acetylglucosamine pyrophosphorylase) were overexpressed.


Correlation between the acid-base properties of the La2O3 catalyst and its methane reactivity.
Density functional theory and coupled cluster theory calculations were carried out to study the effects of the acid-base properties of the La2O3 catalyst on its catalytic activity in the oxidative coupling of methane (OCM) reaction. The La(3+)-O(2-) pair site for CH4 activation is considered as a Lewis acid-Brönsted base pair. Using the Lewis acidity and the Brönsted basicity in the fluoride affinity and proton affinity scales as quantitative measures of the acid-base properties, the energy barrier for CH4 activation at the pair site can be linearly correlated with these acid-base properties. The pair site consisting of a strong Lewis acid La(3+) site and a strong Brönsted base O(2-) site is the most reactive for CH4 activation. In addition, the basicity of the La2O3 catalyst was traditionally measured by temperature-programmed desorption of CO2, but the CO2 chemisorption energy is better regarded as a combined measure of the acid-base properties of the pair site. A linear relationship of superior quality was found between the energy barrier for CH4 activation and the CO2 chemisorption energy, and the pair site favorable for CO2 chemisorption is also more reactive for CH4 activation, leading to the conflicting role of the "basicity" of the La2O3 catalyst in the OCM reaction. The necessity for very high reaction temperatures in the OCM reaction is rationalized by the requirement for the recovery of the most reactive acid-base pair site, which unfortunately also reacts most readily with the byproduct CO2 to form the very stable CO3(2-) species.


Bronchoscopic administration of bovine natural surfactant in ARDS and septic shock: impact on biophysical and biochemical surfactant properties.
The purpose of the present study was to investigate the impact of bronchoscopic surfactant administration, on the biochemical and biophysical surfactant properties, in patients with severe and early acute respiratory distress syndrome (ARDS) and septic shock. A total number of 27 ARDS patients received 300-500 mg x kg x body x weight(-1) of a natural bovine surfactant extract (Alveofact) via a flexible bronchoscope. Bronchoalveolar lavages were performed 3 h prior to, and 15-18 h and 72 h after surfactant administration. A comparison to healthy volunteers, undergoing an identical lavage procedure, was made (control, n=12). Severe biophysical and biochemical surfactant abnormalities were encountered throughout in the ARDS patients. These included a massive alveolar protein load, a reduced percentage of large surfactant aggregates (LA), a loss of palmitoylated phosphatidylcholine species and a significant reduction of surfactant apoprotein (SP)-A, SP-B and SP-C in the LA fraction. Both minimum (gammamin) and adsorption (gammaads) surface tension values (pulsating bubble surfactometer) were dramatically increased. Surfactant treatment resulted in a marked increase in the lavagable phospholipid (PL) pool, but predominance of the alveolar surfactant-inhibitory protein load was still encountered. Far-reaching or even complete normalization of the PL profile, the LA fraction and its SP-B and SP-C (but not SP-A) content as well as the fatty acid composition of the phosphatidylcholine class was noted. Surface tension lowering properties (gammamin and gammaads) significantly improved, but were still not fully normalized. Bronchoscopic administration of large quantities of natural bovine surfactant in severe acute respiratory distress syndrome causes far-reaching restoration of biochemical surfactant properties and significant improvement, however not full normalization, of biophysical surfactant function.


[Metabolic pool of free amino acids in the blood and cerebrospinal fluid of patients with pituitary adenoma before and after proton therapy].
A pool of free amino acids was studied in blood and cerebrospinal fluid of 34 patients with adenoma of hypophysis before proton therapy and within 3 years after the treatment. The course of proton therapy was shown to cause a regression of the disease, a decrease in content of somatotropic hormone in blood as well as to normalize the metabolic pool of amino acids in blood and cerebrospinal fluid.


Arsenic trioxide and all-trans-retinoic acid selectively exert synergistic cytotoxicity against FLT3-ITD AML cells via co-inhibition of FLT3 signaling pathways.
FLT3-ITD mutations occur in approximately 30% of acute myeloid leukemia (AML) and are associated with a poor outcome. Currently available FLT3 inhibitors have in vitro but limited clinical activity in FLT3-ITD AML. Reports have shown that an arsenic trioxide (ATO)/all-trans-retinoic acid (ATRA) combination improves prognosis in acute promyelocytic leukemia, especially with FLT3-ITD, and ATO or ATRA alone enhances apoptosis in FLT3-ITD AML cells treated with FLT3 inhibitors, providing a rationale to investigate the role of ATO/ATRA in FLT3-ITD AML. Here, we demonstrate that an ATO/ATRA combination selectively exerts synergistic cytotoxicity against FLT3-ITD AML cell lines (MV4;11/MOLM-13). The signaling pathways affected by ATO/ATRA include FLT3/STAT5/MYC, FLT3/STAT5/E2F1, FLT3/ERK/ATF5 and FLT3/AKT/ATF5.ATF5 may function as an oncogene in FLT3-ITD AML. Our findings provide experimental evidence that supports further exploration of ATO/ATRA in FLT3-ITD AML in vivo and warrants a clinical evaluation of regimens comprising an ATO/ATRA combination.


Clinical Outcomes and Disease Burden in Amyloidosis Patients with and Without Atrial Fibrillation-Insight from the National Inpatient Sample Database.
Amyloidosis is a systemic illness that affects multiple organ systems, including the cardiovascular, renal, gastrointestinal, and pulmonary systems. Common manifestations include restrictive cardiomyopathy, arrhythmias, nephrotic syndrome, and gastrointestinal hemorrhage. It is unknown whether coexisting atrial fibrillation (AF) worsens the disease burden and outcomes in patients with systemic amyloidosis. In this study, those with a diagnosis of amyloidosis with and without coexisting AF were identified by querying the Healthcare Cost and Utilization Project-specifically, the National Inpatient Sample for the year 2016-based on International Classification of Diseases, 10th Revision, Clinical Modification codes. During 2016, a total of 2,997 patients were admitted with a diagnosis of amyloidosis, including 918 with concurrent AF. Greater rates of mortality (7.4% vs. 5.6%); heart block (6.8% vs. 2.8%); cardiogenic shock (5% vs. 1.6%); placement of an implantable cardioverter-defibrillator, cardiac resynchronization therapy device, or permanent pacemaker (14.5% vs. 4.5%); renal failure (29% vs. 21%); heart failure (66% vs. 30%); and bleeding complications (5.7% vs. 2.8%) were observed in patients with a diagnosis of amyloidosis and coexisting AF when compared with in patients without AF. Interestingly, patients with amyloidosis without comorbid AF had greater odds of associated stroke relative to those with concurrent AF (7.9% vs. 3.4%).


[Non invasive cardiac imaging: clinical role of newly developed modalities. Part III: non ischemic cardiac diseases].
Echocardiography is the preferred initial noninvasive test to assess heart muscle and heart valves. Cardiac MRI has a unique capacity to directly characterise myocardial tissue with specific imaging sequences and late enhancement pattern after gadolinium injection, and has a specific role in the diagnosis of cardiomyopathies. In valvular heart diseases, cardiac MRI precisely measures the severity of aortic or pulmonary regurgitation. In pericardial heart diseases, and specifically when constrictive pericarditis is suspected, cardiac MRI and/or CT are useful to look for pericardial thickening. Cardiac CT and MRI are very rapidly developing techniques in cardiology; the use of these expensive techniques must follow the currently accepted indications in order to be integrated in a rational diagnosis process in clinical practice.


[Congenital dysplasia of the hip in children of immigrants from developing countries].
Aim of study was to ascertain the possible presence of congenital dysplasia of the hip in infants (CDH) in the population immigrated from countries where the problem is surely neglected from the local health service and estimate its incidence. Moreover to observe the impact of the CDH problem on the parents of these children, sometimes of scarce culture or rather of scarce comprehension of the language. Finally, to verify the answer of parents to the medical prescriptions and to the not simple therapeutic formality. From 1989 to 1996, the hip has been examined by Graf ultrasounds (US) method on a population of 181 infants born from developing countries' immigrants in Italy; 77 of them were Egyptians. Even if the density of the population studied was not very high, the results presented in this paper are innovative and differ from the literature on this matter. Among the 362 hips examined with US, only 5 hips were found to be pathologic (4 Egyptians and 1 Philippine; 2 type uD and 3 type IIC of Graf), and they were treated and recovered with a harm in about 3 months. This work underlines the necessity that all immigrated infants should be studied with US hip exams and that CDH in these people should not be under-evaluated: the very low occurrence of this pathology in developing countries is probably mainly due to scarsity of studies on this matter. This allows not only to avoid hip dislocation in these subjects, but also to the society to avoid the necessary cost of the subsequent treatment of well more serious diseases such as osteoarthritis of the hip on dysplastic basis, in subjects that likely will stay in our country definitely, becoming Italian citizens to all effects.


Decline of high hepatitis C virus prevalence in a hemodialysis unit with no isolation measures during a 6-year follow-up.
It has been recently suggested that isolation measures may be necessary to avoid hepatitis C virus (HCV) spread in hemodialysis units with a high HCV prevalence. To assess the variation in prevalence and long-term incidence of HCV infection, we studied our hemodialysis patients during a 6-year follow-up period. We compared anti-HCV prevalence in 1994, 1996, 1998 and 2000 according to the anti-HCV status, and we analyzed the seroconversion of anti-HCV. Strict adherence to universal precautions has been fulfilled since 1993 and systematic anti-HCV testing in blood donors has been performed since 1994. No isolation measures were adopted. In 1994,22 of 53 (41.5%) patients tested positive for anti-HCV; in 1996, 18 of 67 (26.9%); in 1998,9 of 75 (12.0%); and in 2000, 7 of 82 (8.5%) (p < 0.001). In 2000, 7 of 14 (50.0%) patients who had been attending the unit since 1994 and 0 of 68 (0%) who had entered after 1994 were anti-HCV-positive (p = 0.000). Eight of 1 71 (4.7%) patients who entered the unit and 24 of 142 (16.9%) who left it were anti-HCV-positive (p < 0.001). Two patients became anti-HCV-negative. Seroconversion of anti-HCV was observed in 3 patients. The yearly seroconversion rate was 0.5% during the period 1994-1996 (1 of 98 patients at risk), 0.5% during the period 1996-1998 (1 of 91 patients at risk), and 0.4% during the period 1998-2000 (1 of 120 patients at risk). It was possible to reduce a high HCV prevalence in a hemodialysis unit when a low incidence was achieved without taking isolation measures. All anti-HCV-positive patients in 2000 had been undergoing hemodialysis since 1994.


Neonatal BCG protection against tuberculosis lasts for 20 years in Brazil.
Bacille Calmette-Guérin (BCG) efficacy against pulmonary disease is highly variable; until very recently there was no evidence of protection after 10 years. In the control arm of a trial of efficacy of revaccination of schoolchildren in Brazil we found substantial protection (39%; 95%CI 9-58) of neonatal BCG against all forms of tuberculosis (TB) 15-20 years after vaccination, much longer than previously believed. This confirms recent findings from an earlier trial, and must be considered in the design of trials of new TB vaccines and in policy decisions based on assumed lack of neonatal BCG protection with time.


Walnut-like Porous Core/Shell TiO2 with Hybridized Phases Enabling Fast and Stable Lithium Storage.
TiO2 is a promising and safe anode material for lithium ion batteries (LIBs). However, its practical application has been plagued by its poor rate capability and cycling properties. Herein, we successfully demonstrate a novel structured TiO2 anode with excellent rate capability and ultralong cycle life. The TiO2 material reported here shows a walnut-like porous core/shell structure with hybridized anatase/amorphous phases. The effective synergy of the unique walnut-like porous core/shell structure, the phase hybridization with nanoscale coherent heterointerfaces, and the presence of minor carbon species endows the TiO2 material with superior lithium storage properties in terms of high capacity (∼177 mA h g-1 at 1 C, 1 C = 170 mA g-1), good rate capability (62 mA h g-1 at 100 C), and excellent cycling stability (∼83 mA h g-1 was retained over 10 000 cycles at 10 C with a capacity decay of 0.002% per cycle).


Relationship of interleukin-4 to isotypic distribution of anti-double-stranded DNA antibodies in systemic lupus erythematosus.
IgG subclasses of anti-double-stranded DNA antibodies were determined in 182 patients with systemic lupus erythematosus. All isotypes were detected, but IgG1 and IgG3 were predominant (62 and 51% of the cases, respectively). An average of 64 +/- 27% was IgG1, 16 +/- 22% IgG2, 16 +/- 19% IgG3 and 4 +/- 10% IgG4. The rank order or frequency was IgG1, IgG3, IgG2 and IgG4 in patients with musculoskeletal involvement; IgG1, IgG2, IgG3 and IgG4 in those with renal complications; IgG3, IgG1, IgG2 and IgG4 in those with cutaneous involvement; and IgG1, IgG3, IgG2 and IgG4 in those with hematological manifestations. Interleukin-4 (IL-4) was detectable in 17 of 36 selected patients, as opposed to 1 of 40 normal controls. The percentage of the total autoantibody contributed by IgG1 was significantly higher (p < 0.03) in these patients than in the remainder with undetectable levels of IL-4.


Embryo transfer: its uses and recent developments.
The technique of embryo transfer is now routinely employed in several species and with several objectives. In laboratory animals the technique is used mainly in investigations of reproductive biology, whereas in human beings it is used to overcome specific forms of impaired fertility. Because embryo transfer combined with superovulation of the donor can significantly increase the female reproductive rate its greatest application to date has been in farm animals, in which it is widely used in both research and commercial production. Within the past few years there have been many advances in the techniques used in farm animals, particularly in the area of embryo manipulation. The supply of embryos can now be increased by repeated superovulation and by embryo bisection and there has been significant progress in in vitro fertilisation technology. Deep freeze (-196 degrees C) storage of embryos is now routine and may be combined with direct one-step thawing and removal of cryoprotectant. This technique allows the routine non-surgical transfer of embryos in the field. There is also evidence that a routine non-traumatic procedure for sexing embryos may soon be developed. Identical multiplets or clones have been produced by the microdissection of embryos and more recently by the transfer of nuclei from embryos into unfertilized oocytes. Transgenic animals have been produced by the microinjection of recombinant DNA into one of the pronuclei of single-cell unfertilized ova.


Outbreaks of forest defoliating insects in Japan, 1950-2000.
In Japan, several forest-defoliating insects reach outbreak levels and cause serious defoliation. Stand mortality sometimes occurs after severe defoliation. However, in general, tree mortality caused by insect defoliation is low because of the prevailing moist climate in Japan. Evergreen conifers are more susceptible to tree mortality as a result of insect defoliation whereas deciduous broad-leaved trees are seldom killed. Insect defoliation occurs more frequently in man-made environments such as among shade trees, orchards, and plantations than in natural habitats. Outbreaks of some defoliators tend to occur in stands of a particular age: e.g. outbreaks of the pine caterpillar, Dendrolimus spectabilis Butler (Lepidoptera: Lasiocampidae) occur more frequently in young pine plantations. In contrast, defoliation caused by outbreaks of lepidopterous and hymenopterous pests in larch plantations is more frequent with stand maturation. There is a relationship between outbreaks of some defoliators and altitude above sea level. Most outbreaks of forest defoliators were terminated by insect pathogens that operated in a density-dependent fashion. Since the 1970s, Japan has been prosperous and can afford to buy timber from abroad. More recently, there has been an increasing demand for timber in Japan, that coincides with a huge demand internationally, so that the country will need to produce more timber locally in the future. The increasing pressure on the forestry industry to meet this demand will require more sophisticated methods of pest control coupled with more sustainable methods of silviculture.


Escrutinio para el cáncer de colon: ¿cuál fue el impacto en los primeros 2 años de la pandemia de COVID-19? Experiencia en una clínica privada ambulatoria.
COVID-19 pandemic had a negative impact on colorectal cancer (CRC) screening programs. The care strategy was modified throughout the pandemic, this paper evaluates its impact and short-term consequences. A retrospective, descriptive and cross-sectional study was carried out in a private ambulatory endoscopic center, in average risk subjects. The study compared two periods: pre-pandemic and pandemic (subdivided into pre-vaccination and vaccination). During this period, 54.4% of scheduled colonoscopies were due to the screening program. The average age was 60.4 ± 7 years. Women were 52.0%. The overall cancellation rate was 41.1%, higher during pre-vaccination period. There were no differences in the degree of colonic cleansing, colonoscope exit time, and patient satisfaction. The adenoma detection rate (38.4% vs. 42.8% vs. 36.4%; p = 0.8) and the total number of adenomas (p = 0.02) was statistically significant during the pre-vaccination period. The rate of adenoma/patient showed a higher trend during this period (p = 0.06). The number of colorectal cancers was 10, without differences between periods. In conclusion, the impact of the decrease in screening colonoscopy procedures for CRC detection was similar to what was seen worldwide. In this period no increase in cancer cases, although this effect may be observed in the long term.


Carnitine deficiency among hospitalized pediatric patients: A retrospective study of critically ill patients receiving extracorporeal membrane oxygenation therapy.
The metabolic demands associated with critical illness place patients at risk for nutrition deficits. Carnitine is a small molecule essential for fatty acid oxidation and gluconeogenesis. Secondary carnitine deficiency can have clinically significant complications and has been observed anecdotally in patients receiving extracorporeal membrane oxygenation (ECMO) therapy at our institution. Guidelines for monitoring and supplementing carnitine are lacking. This retrospective study determined whether critically ill pediatric patients receiving ECMO have an increased risk of carnitine deficiency. Acylcarnitine analysis was performed on residual specimens from patients who received ECMO therapy. The control data were a convenience sample gathered by chart review of patients who had been tested for carnitine during a hospitalization. Acylcarnitines were measured in 217 non-ECMO patients and 81 ECMO patients. Carnitine deficiency, based on age-specific reference ranges, was observed in 41% of ECMO cases compared with 21% of non-ECMO cases. Multivariable analysis of age-matched patients identified that the odds of carnitine deficiency were significantly lower among patients on the floor compared with ECMO patients (odds ratio, 0.21; 95% CI, 0.10-0.44). Age-specific frequency of qualitative carnitine deficiency ranged from 15% (patients >5 years old) to 56% (patients 1 week to 1 month old) in ECMO patients and 15% (patients >5 years old) to 34% (patients 1-5 years old) in non-ECMO patients. In this study, ECMO patients were carnitine deficient more frequently compared with other inpatients, with the highest rates of deficiency among ECMO patients between 1 week and 1 month old.


Treatment of spatial neglect in clinical practice: A nationwide survey.
Clinical research has documented a range of evidence-based treatment approaches for spatial neglect (SN), but there is a lack of research on the implementation of treatment into clinical practice. The purpose of this study is to describe the current clinical practice of SN treatment across healthcare sectors including involved professions, methods, timing and sources of evidence. This is the second part of a nationwide, anonymous, open Internet survey that was conducted among healthcare professionals in Denmark on assessment and treatment of SN. A total of 525 healthcare professionals participated in the survey of which 411 (78.3%) reported that SN treatment was provided at their workplace. Occupational and physiotherapist were most often involved in the treatment, most commonly characterized by training of activities of daily living (ADL), sensoric stimulation and cueing. Less frequently reported were evidence-based methods such as prism adaptation and visual scanning. The overall intensity of the SN treatment varied considerably across sectors and might consequently be inadequate. A minority of the participants consulted clinical research evidence in their choice of SN treatment approaches. There is a profound lack of dissemination and translation of clinical research into current clinical practice, which unarguably leads to an underuse of evidence-based treatment approaches in SN rehabilitation. The results call for international multidisciplinary clinical guidelines for the treatment of SN at different stages of rehabilitation and the tailoring of treatment approaches to the individual patient.


Genome-wide analyses of lung cancer after single high-dose radiation at five time points (2, 6, 12, 24, and 48 h).
Background: An increasing number of clinicians are experimenting with high-dose radiation. This study focuses on the genomic effects of high-dose single-shot radiotherapy and aims to provide a dynamic map for non-small cell lung cancer (NSCLC). Methods: We used whole-transcriptome sequencing to understand the evolution at molecular levels in A549 and H1299 exposed to 10 Gy X-rays at different times (2, 6, 12, 24, and 48 h) in comparison with the no radiation group. Ingenuity pathway analysis, ceRNA analysis, enrichment analysis, and cell cycle experiments are performed for molecular analyses and function analyses. Results: Whole-transcriptome sequencing of NSCLC showed a significant dynamic change after radiotherapy within 48 h. MiR-219-1-3p and miR-221-3p, miR-503-5p, hsa-miR-455-5p, hsa-miR-29-3p, and hsa-miR-339-5p were in the core of the ceRNA related to time change. GO and KEGG analyses of the top 30 mRNA included DNA repair, autophagy, apoptosis, and ferroptosis pathways. Regulation of the cell cycle-related transcription factor E2F1 might have a key role in the early stage of radiotherapy (2.6 h) and in the later stage of autophagy (24 and 48 h). Functions involving different genes/proteins over multiple periods implied a dose of 10 Gy was related to the kidney and liver pathway. Radiation-induced cell cycle arrest at the G2/M phase was evident at 24 h. We also observed the increased expression of CCNB1 at 24 h in PCR and WB experiments. Conclusion: Our transcriptomic and experimental analyses showed a dynamic change after radiation therapy in 48 h and highlighted the key molecules and pathways in NSCLC after high-dose single-shot radiotherapy.


Toward a fully de-identified biomedical information warehouse.
The Information Warehouse at the Ohio State University Medical Center is a comprehensive repository of business, clinical, and research data from various source systems. Data collected here is a valuable resource that facilitates both translational research and personalized healthcare. The use of such data in research is governed by federal privacy regulations with oversight by the Institutional Review Board. In 2006, the Information Warehouse was recognized by the OSU IRB as an "Honest Broker" of clinical data, providing investigators with de-identified or limited datasets under stipulations contained in a signed data use agreement. In order to streamline this process even further, the Information Warehouse is developing a de-identified data warehouse that is suitable for direct user access through a controlled query tool that is aimed to support both research and education activities. In this paper we report our findings on performance evaluation of different de-identification schemes that may be used to ensure regulatory compliance while also facilitating practical database updating and querying. We also discuss how date-shifting in the de-identification process can impact other data elements such as diagnosis and procedure codes and consider a possible solution to those problems.


Design and Evaluation of an Interprofessional Preceptor Development Mini-Fellowship Program.
Health professions preceptors require skills and knowledge to effectively meet the educational needs of interprofessional students in clinical environments. We implemented a mini-fellowship program to enhance the knowledge, skills, and self-efficacy of preceptors teaching students and applying quality improvement (QI) methods across disciplines and patient care settings. The design, implementation, and evaluation of the program were informed by the faculty development literature, principles of adult learning, and preceptor needs. The 3-day program included workshops on curriculum design, clinical teaching methods, QI, social determinants of health, cultural humility, and interprofessional teamwork. Quantitative and qualitative evaluation methods were used including preprogram and postprogram knowledge and self-efficacy surveys, along with end-of-session and program evaluations. Five annual cohorts involving 41 preceptors with varied demographics, professions, and clinical practices completed the mini-fellowship program. Participants' percentage of items answered correctly on a QI knowledge test increased from 79.2% (pretest) to 85.5% (post-test), a gain of 6.3% (90% CI: 2.9-9.7%; P < .003). The average QI self-efficacy scores improved from 2.64 to 3.82, a gain of 1.18 points on a five-point scale (P < .001). The average education/teaching self-efficacy increased from 2.79 to 3.80 on a five-point scale (P < .001). Ultimately, 94% would recommend the program to other preceptors. An interprofessional preceptor development program designed to train clinicians to effectively teach in the clinical setting and to conduct QI projects with students was achievable and effective. This program can serve as a model for academic centers charged with training future health care workers and supporting their community-based preceptors' training needs.


A new species of subgenus Homoneura from Northern China, with information of 12 species newly recorded (Diptera: Lauxaniidae: Homoneura).
Homoneura (Homoneura) hanmaensis sp. nov. is described as new to science and 12 species are recorded from China for the first time: Homoneura (Homoneura) albomarginata Czerny, 1932, Homoneura (H.) biumbrata (Loew, 1847), Homoneura (H.) cerina Shatalkin, 2000, Homoneura (H.) euaresta (Coquillett, 1898), Homoneura (H.) filiola Czerny, 1932, Homoneura (H.) kaszabi Shewell, 1971, Homoneura (H.) lamellata (Becker, 1895), Homoneura (H.) mediospinosa Merz, 2003, Homoneura (H.) patella Shewell, 1971, Homoneura (H.) shewelliana Papp, 1978, Homoneura (H.) spinicauda Sasakawa and Ikeuchi, 1982, Homoneura (H.) tenera (Loew, 1846). A few of photographs and illustrations are provided for eight species. Keys are provided to separate eight species groups and Chinese species of eight species groups of subgenus Homoneura.


Robot-Assisted Insular Depth Electrode Implantation Through Oblique Trajectories: 3-Dimensional Anatomical Nuances, Technique, Accuracy, and Safety.
The insula is a deep cortical structure that has renewed interest in epilepsy investigation. Invasive EEG recordings of this region have been challenging. Robot-assisted stereotactic electroencephalography has improved feasibility and safety of such procedures. To describe technical nuances of three-dimensional (3D) oblique trajectories for insular robot-assisted depth electrode implantation. Fifty patients who underwent robot-assisted depth electrode implantation between June 2017 and December 2018 were retrospectively analyzed. Insular electrodes were implanted through oblique, orthogonal, or parasagittal trajectories. Type of trajectories, accuracy, number of contacts within insular cortex, imaging, and complication rates were analyzed. Cadaveric and computerized tomography/magnetic resonance imaging 3D reconstructions were used to visualize insular anatomy and the technical implications of oblique trajectories. Forty-one patients (98 insular electrodes) were included. Thirty (73.2%) patients had unilateral insular coverage. Average insular electrodes per patient was 2.4. The mean number of contacts was 7.1 (SD ± 2.91) for all trajectories and 8.3 (SD ± 1.51) for oblique insular trajectories. The most frequently used was the oblique trajectory (85 electrodes). Mean entry point error was 1.5 mm (0.2-2.8) and target error was 2.4 mm (0.8-4.0), 2.0 mm (1.1-2.9) for anterior oblique and 2.8 mm (0.8-4.9) for posterior oblique trajectories. There were no complications related to insular electrodes. Oblique trajectories are the preferred method for insular investigation at our institution, maximizing the number of contacts within insular cortex without traversing through sulci or major CSF fissures. Robot-assisted procedures are safe and efficient. 3D understanding of the insula's unique anatomical features can help the surgeon to improve targeting of this structure.


Highly transient stimulated Raman scattering in SrMoO4 under ultrafast laser pumping with a controllable chirp.
For the first time, to the best of our knowledge, we demonstrate highly transient, multiwavelength, single-pass Raman generation with combined frequency shifts on two Raman modes of an SrMoO4 crystal with high total Raman conversion efficiency of up to 48% in conditions of competition with self-phase modulation (SPM). A 58-mm-long SrMoO4 crystal was used as the active medium under pumping by the 1030-nm, 40-µJ laser pulses with controllable dispersive stretching in a range of 0.25-6 ps at negative and positive chirping. The pump pulse chirping was optimized for both high- and low-frequency Raman shifts on the primary (888 cm-1) and secondary (327 cm-1) Raman modes of the crystal. At the optimal conditions, four Stokes components of stimulated Raman scattering (SRS) radiation with high- and low-frequency Raman shifts at the wavelengths of 1066, 1134, 1177, and 1261 nm were efficiently generated.


Unintentionally retained vascular devices: improving recognition and removal.
The increased demand for minimally invasive placement of intravascular medical devices has led to increased procedure-related complications, including retention of all or part of the implanted device. A number of risk factors can predispose to unintentionally retained vascular devices (uRVD); most are technical in etiology. Despite best efforts to insert and remove vascular devices properly, uRVD still occur. Prevention or early identification of uRVD is ideal; however, procedural complications are not always recognized at the time of device insertion or removal. In these cases, early radiologic diagnosis is important to enable expeditious removal and reduction of morbidity, mortality, and medicolegal consequences. The diagnostic radiologist's role is to identify suspected uRVD and ensure proper communication of the findings to the referring clinician. The diagnostic radiologist can implement various strategies to increase detection of uRVD and advise the referring clinician regarding the use of minimally invasive percutaneous techniques for safe removal of uRVD.


[Simultaneous discovery of osteopetrosis in a mother and fetus on the occasion of radiopelvimetry (author's transl)].
On the occasion of radiopelvimetry, requested for suspected narrowed pelvis, osteopetrosis was discovered simultaneously in the mother and fetus. At birth, the child was perfectly normal and subsequently showed no clinical or laboratory disorder apart from diffuse osseous condensation. The genetic enquiry proved difficult owing to the family situation and up to this day it is not complete and definitively stopped. Although the beginning of the osseous disorders starts in the fetus on an average at the 4th to 5th month of pregnancy, Albers-Schonberg disease is exceptionally diagnosed during the parenatal period. In fact, the incidence of osteopetrosis in the population remains low and on the other hand prenatal radiological examinations are sparingly requested for specific clinical indications. It is the simultaneous discovery of the condition in the mother and the fetus which makes this case a novel one. The discovery of the fetal involvement does not permit prediction concerning progress towards a benign or malignant form.


Young woman with hypophosphatasia: A case report.
Hypophosphatasia is a rare inherited disease defined by teeth and bone mineralization impairment leading to depletion of tissue non-specific alkaline phosphatase. We define a young woman diagnosed with hypophosphatasia (after several times alkaline phosphatase levels were low) was discovered following femoral fracture. A 30-year-old woman who presented for a history of early permanent teeth loss during the last 5 years and HPP-like symptoms in family history and bone radiograph verified bowing, deficient mineralization, and symmetrical subtrochanteric stress fractures of femurs was referred to our clinic for further management. Blood test findings defined raised phosphorus levels on two occasions at 6.2 and 5.7 mg/dl and insufficient 25-hydroxy vitamin D level. HPP early diagnosis and adequate treatment, depending on the clinical symptoms along with laboratory tests, could be effective in decreasing the suffering of the disease and side effects.


Oncogenic response of strain A/J mice to inhaled chemicals.
Strain A/J mice were exposed by inhalation for 6 h/d, 5 d/wk, for 6 mo to carbon disulfide, 1,2-dibromoethane, ethylene oxide, naphthalene, nitrogen dioxide, or vinyl chloride. Significant increases in pulmonary adenoma formation were observed following exposure to 300 ppm carbon disulfide; 20 and 50 ppm 1,2-dibromoethane; 70 and 200 ppm ethylene oxide; 10 ppm nitrogen dioxide; and 50, 200, and 500 ppm vinyl chloride compared to control animals. Repeated studies with 1,2-dibromoethane, ethylene oxide, and vinyl chloride gave similarly significant results. Exposure of mice to 30 ppm naphthalene did not elicit a significant adenoma response. Histopathological examination of lungs from animals in these studies revealed multiple alveolar adenomas. Results from earlier studies with these chemicals, using strain A mice and Swiss mice, and bioassay information with rats and mice were compared with these data. These results provide further information for the validation of this in vivo model as a tool for predicting oncogenic potential following chemical exposure.


Loss of 4.5S RNA induces the heat shock response and lambda prophage in Escherichia coli.
During depletion of 4.5S RNA, cells of Escherichia coli displayed a heat shock response that was simultaneous with the first detectable effect on ribosome function and before major effects on cell growth. Either 4.5S RNA is involved directly in regulating the heat shock response, or this particular impairment of protein synthesis uniquely induces the heat shock response. Several hours later, lambda prophage was induced and the cells lysed.


Complete Genome Sequence of Mycoplasma canadense Strain HAZ 360_1 from Bovine Mastitic Milk in Japan.
Bovine mycoplasmal mastitis is spreading quickly among cows. Mycoplasma canadense, a causal species of bovine mastitis, reduces milk quality and quantity via the infiltration of numerous inflammatory cells. Presented here is the complete 693,241-bp genome sequence of M. canadense strain HAZ 360_1, which was isolated in Japan.


Computer-aided detection of solid lung nodules on follow-up MDCT screening: evaluation of detection, tracking, and reading time.
The purpose of this article is to assess detection, tracking, and reading time of solid lung nodules > or = 4 mm on pairs of MDCT chest screening examinations using a computer-aided detection (CAD) system. Of 54 pairs of low-dose MDCT chest examinations (1.25-mm collimation), two chest radiologists in consensus established that 25 examinations contained 52 nodules > or = 4 mm. All paired examinations were interpreted on the CAD workstation--first without and then with CAD input--for the detection and tracking of lung nodules. A subset of 33 examination pairs was later read on the clinical workstation used in daily practice, and the results were compared for reading time with those on the CAD workstation. After CAD input, the sensitivity for nodule detection increased statistically significantly for both readers (9.6% and 23%; p < or = 0.025). One cancer initially missed by one radiologist was correctly identified with CAD input. The overall reading time on the CAD workstation and clinical workstation was comparable for both radiologists. On average, readers spent 4-5 minutes per case to read the paired examinations on the CAD workstation and 6-8 seconds per CAD mark. The CAD system successfully matched 91.3% of nodules detected in both examinations. The overall rate of available CAD growth assessment was 54.9% of all nodule pairs. In the context of temporal comparison of MDCT screening examinations, the sensitivity of radiologists for detecting lung nodules > or = 4 mm increased significantly (p < or = 0.025) with CAD input without compromising reading time.


Unreliable medical information on birth certificates.
To compare selected maternal, obstetric and newborn medical information on live birth certificates to medical record abstracted data. The Florida Department of Health provided a computer tape containing the Hillsborough County Florida live birth certificate data for July 1, 1992, through December 31, 1996. This information was compared to selected maternal, obstetric and newborn medical data abstracted from the hospital records of women who delivered in that county. Three hospitals provided care for 75% (44,654) of all deliveries in the county in the study period. There were no differences in age, race, gravidity or parity of patients between the data sets. There was no concurrence between the number of patients on the state-compiled birth certificate data and the medical record data in 8 maternal medical complications, 5 complications of labor and delivery, 3 obstetric procedures, 3 abnormal neonatal conditions or 7 congenital anomalies from any hospitals. There was no difference between the three hospitals in the incidence of mismatches. The medical information on the birth certificates from this county was discrepant from that abstracted directly from the patients' medical records. Caution is required in drawing conclusions from these data sets.


An audit of smoking behaviours among patients attending two general dental practices in South Wales: an awareness-raising exercise for the dental team and patients.
This audit aimed to quantify the number of smokers attending two general dental practices. It also aimed to establish the demographic characteristics of these smokers in terms of age, gender and deprivation status, and to raise the awareness of practice staff about smoking cessation. Data were collected from consecutive patients (aged over 16 years) attending two general dental practices over a period of one month. The information collected included smoking status, number of cigarettes smoked, age, gender, and postcode. A deprivation score (derived from the Welsh Index of Multiple Deprivation [WIMD] for 2008) was appended to each patient record in order to provide a measure of deprivation based on the postcode of the patient. Staff at both practices were involved in the audit. Staff were given a brief pre- and post-audit questionnaire to test their knowledge on smoking cessation. The audit standard was that no more than 29% of patients should be smokers. Where relevant, data were statistically tested using the chi-square test. Five hundred and sixty-one patients provided data on their smoking habits. It was found that 159 (28.3%) were smokers, smoking on average 12 cigarettes per day. The average age of the sample was 46 years and 242 (43.1%) were male. Forty-eight per cent of the sample was shown to be resident in a postcode considered to be deprived. Older patients were more likely to be nonsmokers (P=0.0001). Following the final audit meeting, correct answers among staff for knowledge of the National Institute for Health and Clinical Excellence guidelines regarding effective smoking-cessation practices improved from 6% to 71%. The issue of smoking cessation has been highlighted for two dental teams. Whether the audit will result in the delivery of smoking-cessation procedures within the dental practice settings cannot be established. It is clear that the desired smoking-cessation behaviours can now be contemplated by the dental teams. Further monitoring is required to establish outcomes as a result of the actions of the teams.


LEAFY COTYLEDON1-CASEIN KINASE I-TCP15-PHYTOCHROME INTERACTING FACTOR4 Network Regulates Somatic Embryogenesis by Regulating Auxin Homeostasis.
Somatic embryogenesis (SE) is an efficient tool for the propagation of plant species and also, a useful model for studying the regulatory networks in embryo development. However, the regulatory networks underlying the transition from nonembryogenic callus to somatic embryos during SE remain poorly understood. Here, we describe an upland cotton (Gossypium hirsutum) CASEIN KINASE I gene, GhCKI, which is a unique key regulatory factor that strongly affects SE. Overexpressing GhCKI halted the formation of embryoids and plant regeneration because of a block in the transition from nonembryogenic callus to somatic embryos. In contrast, defective GhCKI in plants facilitated SE. To better understand the mechanism by which GhCKI regulates SE, the regulatory network was analyzed. A direct upstream negative regulator protein, cotton LEAFY COTYLEDON1, was identified to be targeted to a cis-element, CTTTTC, in the promoter of GhCKI. Moreover, GhCKI interacted with and phosphorylated cotton CINCINNATA-like TEOSINTE BRANCHED1-CYCLOIDEA-PCF transcription factor15 by coordinately regulating the expression of cotton PHYTOCHROME INTERACTING FACTOR4, finally disrupting auxin homeostasis, which led to increased cell proliferation and aborted somatic embryo formation in GhCKI-overexpressing somatic cells. Our results show a complex process of SE that is negatively regulated by GhCKI through a complex regulatory network.


Progress toward strengthening blood transfusion services--14 countries, 2003-2007.
Nearly all persons transfused with human immunodeficiency virus (HIV)-infected blood become infected, and blood transfusions are a substantial source of HIV transmission in sub-Saharan Africa, especially among women and children. Since 2004, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) has provided technical and financial support to strengthen national blood transfusion services in 14 countries in Africa and the Caribbean with high prevalence of HIV infection. PEPFAR has supported efforts to improve blood supply adequacy and safety by providing policy guidance, strengthening laboratory infrastructure, and enhancing blood donor recruitment and retention practices. To assess the progress made by these countries with PEPFAR support, CDC analyzed data collected by national blood transfusion services in the 14 countries during 2003-2007. This report summarizes the results of that analysis, which found that 1) national policies had been established in 12 of the 14 countries; 2) the number of whole blood units collected had increased in all 14 countries; 3) the percentage of collections from voluntary, non-remunerated donors had increased; and 4) the percentage of collected blood units reactive for HIV had decreased in 13 of the 14 countries. Since the start of the PEPFAR initiative, progress toward improving safe and adequate supplies of blood has been made in the 14 countries with high prevalence of HIV infection.


Cost-Effectiveness of Blood-Based Brain Biomarkers for Screening Adults with Mild Traumatic Brain Injury in the French Health Care Setting.
Two blood-based brain biomarker tests such as the combination of glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 (GFAP+UCH-L1) or S100B have potential to reduce the need for head computed tomography (CT) scanning in patients with mild traumatic brain injury (mTBI). We assessed the clinical and economic impact of using GFAP+UCH-L1 versus CT scan and GFAP+UCH-L1 versus S100B to screen adults with suspected mTBI presenting to an emergency department (ED). A decision model was developed to estimate costs and health outcomes of GFAP+UCH-L1, CT scan, and S100B associated with these screening protocols. Model parameters were extracted from peer-reviewed articles, clinical guidelines, and expert opinion. Analysis was performed from a French health care system perspective (costs in 2020 euros). In the model, patients with a positive biomarker receive a CT scan to confirm the presence of intracranial lesions (ICLs). Depending on clinical state and biomarker and CT results, patients were discharged immediately, kept for observation in the ED, admitted for in-hospital stay and observation, or admitted for surgical management. Incorrect test results may lead to delayed treatment and poor outcomes or overtreatment. GFAP+UCH-L1 use was associated with an overall decrease in CT scans when compared with CT screening or S100B use (325.42 and 46.43 CTs per 1000 patients, respectively). The use of GFAP+UCH-L1 resulted in modest cost savings when compared with CT scanning and with S100B. In all cases, use of GFAP+UCH-L1 marginally improved quality-adjusted life-years (QALYs) and outcomes. Thus, screening with GFAP+UCH-L1 reduced the need for CT scans when compared with systematic CT scan screening or use of S100B while maintaining similar costs and health outcomes.


[Epidemiologic cross-sectional study of the prevalence of chronic bronchitis and lung function disorders in swine breeders and milkers].
In an epidemiological cross-sectional study the influence of occupation in swine production confinements on development of chronic bronchitis and lung function impairments was investigated. The study population comprised 307 swine confinement workers and 165 cattle workers without significant differences in age distribution and smoking habits. For evaluation of respiratory symptoms a standardized questionnaire was used. The following lung function tests were carried out: FVC, FEV1, RV, MEF25, MEF50, PEF and Raw. Regarding the prevalence of chronic bronchitis and lung function impairments no statistically significant differences were found between the two groups. Indeed swine confinement workers indicated a distinct trend to a higher prevalence of chronic bronchitis in correlation to the duration of employment. Workers in swine confinement buildings with more than 10 y exposure showed significantly worse mean values of the measured lung function parameters and significantly more frequent pathological lung function values than the control group of cattle workers.


Generation of Myeloid Cells in Cancer: The Spleen Matters.
Myeloid cells are key components of the tumor microenvironment and critical regulators of disease progression. These innate immune cells are usually short-lived and require constant replenishment. Emerging evidence indicates that tumors alter the host hematopoietic system and induce the biased differentiation of myeloid cells to tip the balance of the systemic immune activities toward tumor-promoting functions. Altered myelopoiesis is not restricted to the bone marrow and also occurs in extramedullary organs. In this review, we outline the recent advances in the field of cancer-associated myelopoiesis, with a focus on the spleen, the major site of extramedullary hematopoiesis in the cancer setting. We discuss the functional specialization, distinct mechanisms, and clinical relevance of cancer-associated myeloid cell generation from early progenitors in the spleen and its potential as a novel therapeutic target.


Double duct-to-mucosa pancreaticojejunostomy for bifid pancreatic duct.
We report a pancreaticojejunostomy with double duct-to-mucosa anastomotic technique after pyloruspreserving pancreaticoduodenectomy for chronic pancreatitis with bifid pancreatic duct. A 49-year-old Japanese man was diagnosed preoperatively as having chronic pancreatitis with common bile duct stricture and pseudocyst of the pancreatic head. In a pancreaticoduodenectomy, the main pancreatic duct (7mm in diameter) and a secondary pancreatic duct (4mm in diameter) were identified intraoperatively at the transected surface. Pancreatography showed the main pancreatic duct as well as thesecondary pancreatic duct that drained the remaining dorsal pancreas, allowing us to diagnose bifid pancreatic duct. The pancreaticojejunostomy was performed in an end-to-side manner to create double duct-to-mucosa anastomoses and to approximate the pancreatic parenchyma and jejunal seromuscular layers. Although bifid pancreatic duct is a rare anatomical anomaly, it behooves every surgeon who performs pancreatic resections to be aware of this entity and the techniques for dealing with it.


Volume Measurement by Diffusion-Weighted Imaging in Cervical Cancer.
The aim of this paper was to evaluate the validity of tumor volume measurement using diffusion-weighted (DW) imaging in cervical cancer. In this retrospective study, 22 patients, who underwent preoperative 3.0 T MR examinations with DW imaging were evaluated. Tumor volume measurement by oblique axial (short axis to the uterine cervix) T2-weighted imaging was performed by manually outlining the tumor on the monitor. The area of tumor in each slice was multiplied by the slice profile (slice thickness plus intersection gap), and the total tumor volume was calculated by summation of these obtained volumes. Meanwhile, one experienced radiological technologist generated three-dimensional DW images of cervical cancer using a volume-rendering algorithm at a computer workstation, and tumor volume was automatically calculated in the workstation. Analysis via the intraclass correlation coefficient (ICC) and Bland-Altman plots were used to assess the validity and reliability of these methods. Between tumor volumes measured by T2-weighted imaging methods and DW imaging methods, the ICC was excellent (0.962). The 95% limits of agreement of volume measurement were -52.7 and 35.7 mL (mean difference, -8.5 mL). In regards to intra-observer variability, the ICC was excellent (0.963). The 95% limits of agreement of volume measurement were -42.2 and 47.4 mL (mean difference, 2.6 mL). DW imaging can be used to measure cervical cancer volume.


Determination of Carbonyl Functional Groups in Bio-oils by Potentiometric Titration: The Faix Method.
Carbonyl compounds present in bio-oils are known to be responsible for bio-oil property changes upon storage and during upgrading. Specifically, carbonyls cause an increase in viscosity (often referred to as 'aging') during storage of bio-oils. As such, carbonyl content has previously been used as a method of tracking bio-oil aging and condensation reactions with less variability than viscosity measurements. Additionally, carbonyls are also responsible for coke formation in bio-oil upgrading processes. Given the importance of carbonyls in bio-oils, accurate analytical methods for their quantification are very important for the bio-oil community. Potentiometric titration methods based on carbonyl oximation have long been used for the determination of carbonyl content in pyrolysis bio-oils. Here, we present a modification of the traditional carbonyl oximation procedures that results in less reaction time, smaller sample size, higher precision, and more accurate carbonyl determinations. While traditional carbonyl oximation methods occur at room temperature, the Faix method presented here occurs at an elevated temperature of 80 °C.


[Expression of Tcf-4, MMP7 and Survivin in Colorectal Cancer and Its Clinical Significance].
To explore the clinical and pathological significance and correlations among the xpressions of Tcf-4, MMP7 and survivin in colorectal cancer. The expressions of Tcf-4, MMP7 and survivin mRNA in tumor tissues and adjacent normal mucosa from 50 colorectal cancer patients were detected by reverse transcription PCR (RT-PCR). The expressed proteins of Tcf-4, MMP7 and survivin were measured using mmunohistochemistry staining technique (Elivision) in 100 colorectal cancer samples and 60 normal mucosa tissue samples. We analyzed the correlations between those measurements and their associations with clinical and pathological characteristics. Positive expressions of Tcf-4, MMP7 and survivin mRNA were found in both cancer and adjacent mucosa tissues, despite a higher level of expression in the cancer tissues (P < 0.01). Expressed proteins were detected in cancer tissues of 69.00% (69/100) of those with a positive Tcf-4 expression, 77.00% (77/100) of those with a positive MMP7 expression, and 65.00% (65/100) of those with a positive survivin expression. Compared with cancer tissues, lower levels of protein expression were found in normal mucosa tissues [16.67% (10/60) for Tcf-4, 13.33% (8/60) for MMP7 and 15.00% (9/60) for survivin, P < 0.01]. The expressions of Tcf-4, MMP7 and survivin were all associated with lymphatic metastasis and Dukes staging (P < 0.05). MMP7 expression was associated with depth of tumor invasion (P < 0.05). Survivin expression was associated with tumor differentiation. The Spearman rank correlation analyses showed that protein expressions in colorectal cancer tissues in those with a positive Tcf-4 were correlated with those with a positive MMP7 (r = 0.302) and those with a positive survivin (r = 0.279) (P < 0.01), but not in those with a positive MMP7 and those with a positive survivin (r = 0.097, P > 0.05). The expression levels of Tcf-4, MMP7 and survivin are high in colorectal cancer, all being linked to lymph node metastasis and Dukes stages of patients. This suggests that they may be involved in the occurrence, development, malignant growth and clinical progression of colorectal cancer.


A New Linkage between the Tumor Suppressor RKIP and Autophagy: Targeted Therapeutics.
The complexities of molecular signaling in cancer cells have been hypothesized to mediate cross-network alterations of oncogenic processes such as uncontrolled cell growth, proliferation, acquisition of epithelial-to-mesenchymal transition (EMT) markers, and resistance to cytotoxic therapies. The two biochemically exclusive processes/proteins examined in the present review are the metastasis suppressor Raf-1 kinase inhibitory protein (RKIP) and the cell-intrinsic system of macroautophagy (hereafter referred to as autophagy). RKIP is poorly expressed in human cancer tissues, and low expression levels are correlated with high incidence of tumor growth, metastasis, poor treatment efficacy, and poor prognoses in cancer patients. By comparison, autophagy is a conserved cytoprotective degradation pathway that has been shown to influence the acquisition of resistance to hypoxia and nutrient depletion as well as the regulation of chemo-immuno-resistance and apoptotic evasion. Evidently, a broad library of cancer-relevant studies exists for RKIP and autophagy, although reports of the interactions between pathways involving RKIP and autophagy have been relatively sparse. To circumvent this limitation, the coordinate regulatory and effector mechanisms were examined for both RKIP and autophagy. Here, we propose three putative pathways that demonstrate the inherent pleiotropism and relevance of RKIP and the microtubule-associated protein 1 light chain 3 (MAP1LC3, LC3) on cell growth, proliferation, senescence, and EMT, among the hallmarks of cancer. Our findings suggest that signaling modules involving p53, signal transducer and activator of transcription 3 (STAT3), nuclear factor-κB (NF-κB), and Snail highlight the novel roles for RKIP in the control of autophagy and vice versa. The suggested potential crosstalk mechanisms are new areas of research in which to further study RKIP and autophagy in cancer models. These should lead to novel prognostic motifs and will provide alternative therapeutic strategies for the treatment of unresponsive aggressive cancer types.


Motor and autonomic concomitant health improvements with neuromodulation and exercise (MACHINE) training: a randomised controlled trial in individuals with spinal cord injury.
Motor and autonomic dysfunctions are widespread among people with spinal cord injury (SCI), leading to poor health and reduced quality of life. Exercise interventions, such as locomotor training (LT), can promote sensorimotor and autonomic recovery post SCI. Recently, breakthroughs in SCI research have reported beneficial effects of electrical spinal cord stimulation (SCS) on motor and autonomic functions. Despite literature supporting the independent benefits of transcutaneous SCS (TSCS) and LT, the effect of pairing TSCS with LT is unknown. These therapies are non-invasive, customisable and have the potential to simultaneously benefit both sensorimotor and autonomic functions. The aim of this study is to assess the effects of LT paired with TSCS in people with chronic SCI on outcomes of sensorimotor and autonomic function. Twelve eligible participants with chronic (>1 year) motor-complete SCI, at or above the sixth thoracic segment, will be enrolled in this single-blinded, randomised sham-controlled trial. Participants will undergo mapping for optimisation of stimulation parameters and baseline assessments of motor and autonomic functions. Participants will then be randomly assigned to either LT+TSCS or LT+Sham stimulation for 12 weeks, after which postintervention assessments will be performed to determine the effect of TSCS on motor and autonomic functions. The primary outcome of interest is attempted voluntary muscle activation using surface electromyography. The secondary outcomes relate to sensorimotor function, cardiovascular function, pelvic organ function and health-related quality of life. Statistical analysis will be performed using two-way repeated measures Analysis of variance (ANOVAs) or Kruskal-Wallis and Cohen's effect sizes. This study has been approved after full ethical review by the University of British Columbia's Research Ethics Board. The stimulator used in this trial has received Investigation Testing Authorisation from Health Canada. Trial results will be disseminated through peer-reviewed publications, conference presentations and seminars. NCT04726059.


Methane and Nitrous Oxide Emissions from Flooded Rice Systems following the End-of-Season Drain.
Large CH and NO fluxes can occur from flooded rice ( L.) systems following end-of-season drainage, which contribute significantly to the total growing-season greenhouse gas (GHG) emissions. Field and laboratory studies were conducted to determine under what soil water conditions these emissions occur. In three field studies, GHG fluxes and dissolved CH in the soil pore water were measured before and after drainage. Across all fields, approximately 10% of the total seasonal CH emissions and 27% of the total seasonal NO emissions occurred following the final drain, confirming the importance of quantifying postdrainage CH and NO emissions. Preplant fertilizer N had no effect on CH emissions or dissolved CH; however, increased postdrainage NO fluxes were observed at higher N rates. To determine when postdrainage sampling needs to take place, our laboratory incubation study measured CH and NO fluxes from intact soil cores from these fields as the soil dried. Across fields, maximum CH emissions occurred at approximately 88% water-filled pore space (WFPS), but emissions were observed between 47 and 156% WFPS. In contrast, maximum NO emissions occurred between 45 and 71% WFPS and were observed between 16 and 109% WFPS. For all fields, gas samplings between 76 and 100% WFPS for CH emissions and between 43 and 78% WFPS for NO emissions was necessary to capture 95% of these postdrainage emissions. We recommend that frequent gas sampling following drainage be included in the GHG protocol of total GHG emissions.


Providing a Single Ground-Truth for Illuminant Estimation for the ColorChecker Dataset.
The ColorChecker dataset is one of the most widely used image sets for evaluating and ranking illuminant estimation algorithms. However, this single set of images has at least 3 different sets of ground-truth (i.e., correct answers) associated with it. In the literature it is often asserted that one algorithm is better than another when the algorithms in question have been tuned and tested with the different ground-truths. In this short correspondence we present some of the background as to why the 3 existing ground-truths are different and go on to make a new single and recommended set of correct answers. Experiments reinforce the importance of this work in that we show that the total ordering of a set of algorithms may be reversed depending on whether we use the new or legacy ground-truth data.


Predictors of cytomegalovirus disease among pediatric transplant recipients within one year of renal transplantation.
Cytomegalovirus (CMV) is the most important opportunistic infection in renal transplant recipients and is associated with an increased risk of rejection. Infection can be acquired post-operatively (from the transplanted organ) or from re-activation of latent disease. To identify risk factors for CMV disease in a pediatric population within 1 yr of renal transplant, and to generate hypotheses for the pathogenesis of CMV disease in this population, a review of all recipients from 1992 to 1998 in a children's hospital in Atlanta, Georgia, was undertaken. Medical records of 73 transplants performed on 72 patients were reviewed: nine (12.7%) of 72 individuals, after 73 procedures developed CMV disease. Median time to onset of CMV disease was 52 days post-transplant (range = 15-95 days). Receipts of mycophenolate mofetil (MMF), demographic factors, and use of cadaveric kidneys were not associated with a significantly elevated risk of CMV disease. Positive donor CMV serostatus was associated with CMV disease (uni-variate relative risk [RR] = 8.52, Fisher's Exact Test [FET] p = 0.010). Patients with transplants in October or November had a higher risk of developing CMV disease (four of 13; 30.8%) than patients transplanted in other months (five of 60, 8.3%); RR = 3.69; p = 0.047, FET). Most transplants of patients who did not develop CMV disease were performed in January through August (48/64; 75.0%); only 25.0% were performed in September through December. In contrast, six of nine (66.7%) transplants in patients who subsequently developed CMV disease were performed in September through December (p = 0.018, FET). Donor CMV-positive serostatus and transplant in October and November continued to be independently associated with an increased risk of CMV disease when controlled for other factors. The association of transplant in October and November with CMV disease in November-January may be related to an increased risk of seasonal community CMV exposure and primary CMV infection during the peak season for CMV circulation, with subsequent immune suppression promoting progression to disease. Alternatively, co-infection with seasonal pathogens after exposure from an infected donor during the period of immune suppression may promote progression from CMV infection to CMV disease. Further studies should be undertaken to explore these and other hypotheses, which may have implications for determination of a need for anti-viral prophylaxis.


The economic and environmental cost of delayed GM crop adoption: The case of Australia's GM canola moratorium.
Incorporating socio-economic considerations (SECs) into national biosafety regulations regarding genetically modified (GM) crops have opportunity costs. Australia approved the cultivation of GM canola through a science-based risk assessment in 2003, but allowed state moratoria to be instituted based on potential trade impacts over the period 2004 to 2008 and 2010 in the main canola growing states. This analysis constructs a counterfactual assessment using Canadian GM canola adoption data to create an S-Curve of adoption in Australia to measure the environmental and economic opportunity costs of Australia's SEC-based moratoria between 2004 and 2014. The environmental impacts are measured through the amount of chemical active ingredients applied during pest management, the Environmental Impact Quotient indicator, and greenhouse gas emissions. The economic impacts are measured through the variable costs of the weed control programs, yield and the contribution margin. The environmental opportunity costs from delaying the adoption of GM canola in Australia include an additional 6.5 million kilograms of active ingredients applied to canola land; a 14.3% increase in environmental impact to farmers, consumers and the ecology; 8.7 million litres of diesel fuel burned; and an additional 24.2 million kilograms of greenhouse gas (GHG) and compound emissions released. The economic opportunity costs of the SEC-based moratoria resulted in foregone output of 1.1 million metric tonnes of canola and a net economic loss to canola farmers' of AU$485.6 million. The paper provides some of the first quantified, post-adoption evidence on the opportunity cost and environmental impacts of incorporating SECs into GM crop regulation.


From cysteamine to MPTP: structure-activity studies with duodenal ulcerogens.
Cysteamine is the first chemical identified that induces acute and chronic duodenal ulcers in rodents. Structure-activity studies with cysteamine, propionitrile and their derivatives, as well as with analogues of toluene, revealed numerous alkyl and aryl duodenal ulcerogens. Among these, one of the most interesting from an etiologic and pathogenetic point of view is the dopaminergic neurotoxin MPTP, which shows structural similarities with toluene. The chemically-induced duodenal ulcers are similar and localized on the anterior and posterior wall of the duodenal bulb. Both cysteamine and MPTP affect endogenous dopamine; MPTP is especially potent in depleting central dopamine and inducing lesions in the substantia nigra. MPTP given in high doses induces Parkinson's disease-like syndrome and gastric ulcers. Cysteamine and propionitrile also cause dyskinesia in large and multiple doses. The motility disorders and duodenal ulcers are abolished by dopamine agonists. Cysteamine and MPTP have been known to increase and decrease gastric acid secretion, respectively. However, both compounds induced duodenal dysmotility, decreased bicarbonate production, and reduced its delivery from distal to proximal duodenum. These factors decrease acid neutralization in the duodenal bulb and contribute to duodenal ulceration. Thus, studies with animal models may reveal endogenous mediators and specific receptors which might be involved in the pathogenesis of duodenal ulceration. Specific structure-activity studies in toxicology may lead to new insights in the pathogenesis and pharmacology of a poorly understood human disorder such as duodenal ulceration.


Novel thieno[2,3-d][1,3]oxazin-4-ones as inhibitors of human leukocyte elastase.
A series of thieno[2,3-d][1,3]oxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase. New synthetic routes to 2-alkoxy-, 2-alkylthio-, and 2-sec-amino-substituted derivatives are reported. This study demonstrates the versatility of 2-aminothiophenes prepared by Gewald reaction as a synthetic entry to serine protease-inhibiting, fused 1,3-oxazin-4-ones. Introduction of ethoxy, n-propoxy, and ethylthio groups at C-2 delivered the most potent inhibitors of this series with Ki values lower than 11 nM. Kinetic studies and product analyses revealed the formation of acyl-enzymes as a result of the attack of the active site serine at the carbon C-4 and subsequent deacylation. This mode of action is similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. Replacement of the benzene ring in benzoxazinones by a (substituted) thiophene led to improved hydrolytic stability and retained inhibitory potency.


Molecular characterization of an Italian patient with plasminogen deficiency and ligneous conjunctivitis.
Plasminogen deficiency is a rare disease characterized by ligneous conjunctivitis and infections. We observed a 3-year-old Italian boy presenting ligneous conjunctivitis and low plasma levels of plasminogen. Twenty-three different mutations on the PLG gene have been reported to date, but mutation analysis had been troublesome for the presence of highly homologous genes. The aim of the study was to identify the underlying mutation avoiding coamplification of unwanted genetic materials using a long polymerase chain reaction strategy, instead of the previously reported subcloning methods. By this simple strategy the complete sequence analysis of PLG gene was performed, and a previously reported missense homozygous mutation (K19E) was identified.


A prion-like domain in Hsp42 drives chaperone-facilitated aggregation of misfolded proteins.
Chaperones with aggregase activity promote and organize the aggregation of misfolded proteins and their deposition at specific intracellular sites. This activity represents a novel cytoprotective strategy of protein quality control systems; however, little is known about its mechanism. In yeast, the small heat shock protein Hsp42 orchestrates the stress-induced sequestration of misfolded proteins into cytosolic aggregates (CytoQ). In this study, we show that Hsp42 harbors a prion-like domain (PrLD) and a canonical intrinsically disordered domain (IDD) that act coordinately to promote and control protein aggregation. Hsp42 PrLD is essential for CytoQ formation and is bifunctional, mediating self-association as well as binding to misfolded proteins. Hsp42 IDD confines chaperone and aggregase activity and affects CytoQ numbers and stability in vivo. Hsp42 PrLD and IDD are both crucial for cellular fitness during heat stress, demonstrating the need for sequestering misfolded proteins in a regulated manner.