Traditional Chinese Medicine Tanreqing Inhibits Quorum Sensing Systems in Pseudomonas aeruginosa.
Pseudomonas aeruginosa is an opportunistic pathogen that can infect a wide variety of hosts including humans, plants, and animals. The production of virulence factors is the determinant of the infection paradigm and is under orchestrated regulation via cell-to-cell communication process called quorum sensing (QS). To disable QS circuits and prevent bacterial infections, a large battery of anti-QS agents, particularly from traditional Chinese medicine have been developed. Here, we used P. aeruginosa as a model microorganism to investigate the effect of traditional Chinese medicine Tanreqing (TRQ) formula on bacterial pathogenicity. Phenotypic analysis showed that TRQ treatment could completely inhibit the production of phenazine pyocyanin and moderately inhibit the production of virulence factors such as rhamnolipids, elastase, and alkaline protease. Further transcriptomic analyses revealed that TRQ treatment could significantly attenuate the expression of QS-regulated genes in P. aeruginosa and TRQ-treated P. aeruginosa regulon shared a large overlap with QS regulon. Component contribution to QS inhibition shed light on the indispensable role of all five components in TRQ formula. Further genetic analysis indicated that upstream regulators of QS systems, including two-component systems GacS/GacA and PprA/PprB, were both inhibited by TRQ treatment. Finally, our TRQ formula could efficiently protect Caenorhabditis elegans from killing by P. aeruginosa. Altogether, we have proved TRQ formula as an effective and specific agent to attenuate bacterial virulence and combat bacterial infections.


Unbalanced der(5)t(5;20) translocation associated with megalencephaly, perisylvian polymicrogyria, polydactyly and hydrocephalus.
The combination of megalencephaly, perisylvian polymicrogyria, polydactyly and hydrocephalus (MPPH) is a rare syndrome of unknown cause. We observed two first cousins affected by an MPPH-like phenotype with a submicroscopic chromosome 5q35 deletion as a result of an unbalanced der(5)t(5;20)(q35.2;q13.3) translocation, including the NSD1 Sotos syndrome locus. We describe the phenotype and the deletion breakpoints of the two MPPH-like patients and compare these with five unrelated MPPH and Sotos patients harboring a 5q35 microdeletion. Mapping of the breakpoints in the two cousins was performed by MLPA, FISH, high density SNP-arrays and Q-PCR for the 5q35 deletion and 20q13 duplication. The 5q35 deletion area of the two cousins almost completely overlaps with earlier described patients with an atypical Sotos microdeletion, except for the DRD1 gene. The five unrelated MPPH patients neither showed submicroscopic chromosomal aberrations nor DRD1 mutations. We reviewed the brain MRI of 10 Sotos patients and did not detect polymicrogyria in any of them. In our two cousins, the MPPH-like phenotype is probably caused by the contribution of genes on both chromosome 5q35 and 20q13. Some patients with MPPH may harbor a submicroscopic chromosomal aberration and therefore high-resolution array analysis should be part of the diagnostic workup.


Photosynthetic electron transport from water to NADP driven by photosystem II in inside-out chloroplast vesicles.
It is now widely held that the light-induced noncyclic (linear) electron transport from water to NADP(+) requires the collaboration in series of the two photosystems that operate in oxygen-evolving cells: photosystem II (PSII) photooxidizes water and transfers electrons to photosystem I (PSI); PSI photoreduces ferredoxin, which in turn reduces NADP(+) (the Z scheme). However, a recently described alternative scheme envisions that PSII drives the noncyclic electron transport from water to ferredoxin and NADP(+) without the collaboration of PSI, whose role is limited to cyclic electron transport [Arnon, D. I., Tsujimoto, H. Y. & Tang, G. M.-S. (1981) Proc. Natl. Acad. Sci. USA 78, 2942-2946]. Reported here are findings at variance with the Z scheme and consistent with the alternative scheme. Thylakoid membrane vesicles were isolated from spinach chloroplasts by the two-phase aqueous polymer partition method. Vesicles, originating mainly from appressed chloroplast membranes that are greatly enriched in PSII, were turned inside-out with respect to the original sidedness of the membrane. With added plastocyanin, ferredoxin, and ferredoxin-NADP(+) reductase, the inside-out vesicles enriched in PSII gave a significant photoreduction of NADP(+) with water as electron donor, under experimental conditions that appear to exclude the participation of PSI.


Evidence for four deoxynucleoside kinase activities in extracts of Lactobacillus leichmannii.
Extracts of Lactobacillus leichmannii (ATCC 7830) catalyze the phosphorylation of the four principal deoxynucleosides. Thymidine, deoxyguanosine, and deoxycytidine kinase activities were found to be optimal with deoxyadenosine triphosphate as the phosphoryl donor, whereas deoxycytidine triphosphate was the optimal donor for deoxyadenosine kinase activity. L. leichmannii catalyzes the conversion of deoxycytidine to deoxyuridylic acid, probably by a pathway involving deoxycytidylate deaminase.


Changes in oxidative stress during outpatient surgery.
Reactive oxygen species are associated with tissue inflammation and injury. Our laboratory has demonstrated that ethane, a stable product of lipid peroxidation, in exhaled breath can be used to measure total body oxidative stress. Herein patients were studied who underwent outpatient surgery, laproscopic bilateral tubal ligation (BTL, n = 10) and anterior cruciate ligament (ACL, n = 10) repair of the knee. These surgical procedures were expected to involve mild degrees of ischemia and reperfusion. In each of these cases propofol, an intravenous anesthetic with antioxidant properties, was used. Breath ethane was measured as a biomarker of oxidative stress that occurred at reperfusion of ischemic tissue. Data were analyzed by one-way analysis of variance. Clinically relevant concentrations of propofol were unable to completely block the increase in oxidative stress following reperfusion in either of these minor surgeries. Breath ethane increased significantly after reperfusion in both the BTL (p = 0.03) and the ACL (p = 0.005) patients. Also, the increase in oxidative stress was related to the time of ischemia.


Modification of the frog's electroretinogram by transretinal direct current.
1. Transretinal direct current modifies the amplitude and waveform of the frog's electroretinogram (ERG). Outward current (that flowing from vitreous to sclera) depresses the ERG while inward current enhances it. Outward current causes an apparent reversal of the polarity of the positive off-response (d-wave) of the ERG. 2. A true reversal does not actually occur. Rather, the outward current unmasks a negative off-response by depressing the positive off-response. 3. The positive off-response and the b-wave can be completely abolished by strong outward current, but cannot be reversed. 4. Treatment with ammonia abolishes the negative off-response, leaving a positive off-response which is affected by current in exactly the same way as the normal positive off-response. 5. Two possible mechanisms by which the current could be affecting the amplitude of the positive off-response would require that its amplitude be reversed for strong outward current. The absence of such reversal rejects these mechanisms.


Measurement of patient entrance surface dose rates for fluoroscopic x-ray units.
Measurements of patient entrance surface dose rate provide valuable data for interpreting results from dose-area product studies on fluoroscopic x-ray equipment. Methods for measurement of entrance surface dose rate with backscatter and incident dose rate without backscatter have been investigated. Entrance surface dose rate is measured with an ionization chamber in contact with a tissue-equivalent phantom. Backscattered radiation contributes 27-45% to the measurement and is affected by field size and chamber position. Incident dose rate measured using a copper phantom provides an alternative approach. Consistent relationships between thicknesses of Perspex and copper giving similar incident dose rates under automatic gain control have been established for different tube potentials with and without a grid. This allows measurements of incident dose rate made using copper to be linked to corresponding thicknesses of tissue-equivalent material. Since only a few millimetres of copper are required, contributions from backscatter can be minimized and transport of phantoms is simplified. Incident dose can be related to dose-area product and entrance surface dose derived using backscatter factors. Such measurements play a valuable role in interpreting patient dose data and recommending options to reduce patient dose.


Development of a model to identify patients who do not need oesophageal biopsies when eosinophilic oesophagitis is suspected.
Predictive models for eosinophilic oesophagitis (EoE) may not fully rule in the diagnosis. To develop a reverse model that predicts against EoE to eliminate the need for oesophageal biopsies. In this two-centre study, a predictive model was developed (Mayo Clinic) and validated (University of North Carolina [UNC]). Cross-sectional data from consecutive adult patients without prior EoE who underwent upper enoscopy with oesophageal biopsies were used. EoE cases had ≥15 eosinophils/high-power field while controls had no eosinophils. Data were collected on patient clinical and endoscopic features. Multiple variable logistic regression was used to identify predictors of non-EoE status while maintaining specificity ≥95%. A secondary model was developed to predict against the need for endoscopy in patients suspected of having EoE without alarm symptoms. The Mayo and UNC cohorts consisted of 345 (EoE = 94, non-EoE = 251) and 297 patients (EoE = 84, non-EoE = 213), respectively. A primary model based on clinical and endoscopic features predicted against EoE with c-statistic 0.92 (95% CI: 0.88-0.96), specificity 95%, and sensitivity 65%. This model was validated (UNC) with c-statistic 0.87 (95% CI: 0.82-0.92). A simplified scoring system was created and a threshold of ≥12 points excluded EoE with 95% specificity and 50% sensitivity. A secondary model based on clinical characteristics alone predicted against EoE with c-statistic 0.86 (95% CI: 0.82-0.90), specificity 95% and sensitivity 39% and validated (UNC) with c-statistic 0.78 (95% CI: 0.71-0.85). A simplified scoring system accurately identified a group of patients with a low likelihood of EoE where unnecessary oesophageal biopsies can be avoided, potentially resulting in resource and cost savings.


Investigation on the Effect of Hemodialysis Combined with MDT Multimode Intervention on Renal Fibrosis Degree and Renal Function Improvement in Uremia Patients.
The effect of hemodialysis combined with MDT intervention on the degree of renal fibrosis and renal function in uremia patients was studied. 118 patients with uremia admitted to the hospital were selected as the research object, and they were divided into two groups according to the random number table method, 59 cases in the control group and 59 cases in the experimental group. The control group was treated with hemodialysis, and the experimental group was treated with MDT multimode intervention on the basis of hemodialysis. The differences in renal fibrosis, renal function, and satisfaction after treatment were compared before treatment and at 1, 3, and 6 months after treatment. The experimental results showed that hemodialysis combined with MDT multimode intervention in uremia patients could reduce renal fibrosis and improve renal function and improve clinical satisfaction evaluation.


Assessing motor deficits in compressive neuropathy using quantitative electromyography.
Studying the changes that occur in motor unit potential trains (MUPTs) may provide insight into the extent of motor unit loss and neural re-organization resulting from nerve compression injury. The purpose of this study was to determine the feasibility of using decomposition-based quantitative electromyography (DQEMG) to study the pathophysiological changes associated with compression neuropathy. The model used to examine compression neuropathy was carpal tunnel syndrome (CTS) due to its high prevalence and ease of diagnosis. Surface and concentric needle electromyography data were acquired simultaneously from the abductor pollicis brevis muscle in six individuals with severe CTS, eight individuals with mild CTS and nine healthy control subjects. DQEMG was used to detect intramuscular MUPTs during constant-intensity contractions and to estimate parameters associated with the surface- and needle-detected motor unit potentials (SMUPs and MUPs, respectively). MUP morphology and stability, SMUP morphology and motor unit number estimates (MUNEs) were compared among the groups using Kruskal-Wallis tests. The severe CTS group had larger amplitude and longer duration MUPs and smaller MUNEs than the mild CTS and control groups, suggesting that the individuals with severe CTS had motor unit loss with subsequent collateral reinnervation, and that DQEMG using a constant-intensity protocol was sensitive to these changes. SMUP morphology and MUP complexity and stability did not significantly differ among the groups. These results provide evidence that MUP amplitude parameters and MUNEs obtained using DQEMG, may be a valuable tool to investigate pathophysiological changes in muscles affected by compressive motor neuropathy to augment information obtained from nerve conduction studies. Although there were trends in many of these measures, in this study, MUP complexity and stability and SMUP parameters were, of limited value.


Comparative genomics of the vitamin B12 metabolism and regulation in prokaryotes.
Using comparative analysis of genes, operons, and regulatory elements, we describe the cobalamin (vitamin B12) biosynthetic pathway in available prokaryotic genomes. Here we found a highly conserved RNA secondary structure, the regulatory B12 element, which is widely distributed in the upstream regions of cobalamin biosynthetic/transport genes in eubacteria. In addition, the binding signal (CBL-box) for a hypothetical B12 regulator was identified in some archaea. A search for B12 elements and CBL-boxes and positional analysis identified a large number of new candidate B12-regulated genes in various prokaryotes. Among newly assigned functions associated with the cobalamin biosynthesis, there are several new types of cobalt transporters, ChlI and ChlD subunits of the CobN-dependent cobaltochelatase complex, cobalt reductase BluB, adenosyltransferase PduO, several new proteins linked to the lower ligand assembly pathway, l-threonine kinase PduX, and a large number of other hypothetical proteins. Most missing genes detected within the cobalamin biosynthetic pathways of various bacteria were identified as nonorthologous substitutes. The variable parts of the cobalamin metabolism appear to be the cobalt transport and insertion, the CobG/CbiG- and CobF/CbiD-catalyzed reactions, and the lower ligand synthesis pathway. The most interesting result of analysis of B12 elements is that B12-independent isozymes of the methionine synthase and ribonucleotide reductase are regulated by B12 elements in bacteria that have both B12-dependent and B12-independent isozymes. Moreover, B12 regulons of various bacteria are thought to include enzymes from known B12-dependent or alternative pathways.


An evaluation of mathematical models for the outbreak of COVID-19.
Mathematical modelling performs a vital part in estimating and controlling the recent outbreak of coronavirus disease 2019 (COVID-19). In this epidemic, most countries impose severe intervention measures to contain the spread of COVID-19. The policymakers are forced to make difficult decisions to leverage between health and economic development. How and when to make clinical and public health decisions in an epidemic situation is a challenging question. The most appropriate solution is based on scientific evidence, which is mainly dependent on data and models. So one of the most critical problems during this crisis is whether we can develop reliable epidemiological models to forecast the evolution of the virus and estimate the effectiveness of various intervention measures and their impacts on the economy. There are numerous types of mathematical model for epidemiological diseases. In this paper, we present some critical reviews on mathematical models for the outbreak of COVID-19. Some elementary models are presented as an initial formulation for an epidemic. We give some basic concepts, notations, and foundation for epidemiological modelling. More related works are also introduced and evaluated by considering epidemiological features such as disease tendency, latent effects, susceptibility, basic reproduction numbers, asymptomatic infections, herd immunity, and impact of the interventions.


Endobronchial ultrasound-guided intranodal forceps biopsy (EBUS-IFB)-technical review.
Endobronchial ultrasound (EBUS) and transbronchial needle aspiration (TBNA) have changed the landscape of pulmonology. Mediastinal structures beyond the confines of airway walls are visualized in real-time with EBUS, leading to improved accuracy of tissue sampling and diagnostic yield. With the development of various needle sizes ranging from 25-G to 19-G, the sampling of lymph nodes is becoming easier and more commonplace. Yet, certain conditions such as sarcoidosis and lymphoma may still be difficult to diagnose via EBUS-TBNA. Furthermore, in the age of targeted therapy, there are more demands on EBUS-TBNA samples for molecular marker testing and next-generation sequencing. Here, we present a complementary methodology, EBUS-guided intranodal forceps biopsy (EBUS-IFB), for tissue acquisition that may help address these deficiencies. Specifically, we aim to propose indications, contraindications, outline approaches in performing IFB, and provide an overview of the data for this complementary technique.


Poor transferability of species distribution models for a pelagic predator, the grey petrel, indicates contrasting habitat preferences across ocean basins.
Species distribution models (SDMs) are increasingly applied in conservation management to predict suitable habitat for poorly known populations. High predictive performance of SDMs is evident in validations performed within the model calibration area (interpolation), but few studies have assessed SDM transferability to novel areas (extrapolation), particularly across large spatial scales or pelagic ecosystems. We performed rigorous SDM validation tests on distribution data from three populations of a long-ranging marine predator, the grey petrel Procellaria cinerea, to assess model transferability across the Southern Hemisphere (25-65°S). Oceanographic data were combined with tracks of grey petrels from two remote sub-Antarctic islands (Antipodes and Kerguelen) using boosted regression trees to generate three SDMs: one for each island population, and a combined model. The predictive performance of these models was assessed using withheld tracking data from within the model calibration areas (interpolation), and from a third population, Marion Island (extrapolation). Predictive performance was assessed using k-fold cross validation and point biserial correlation. The two population-specific SDMs included the same predictor variables and suggested birds responded to the same broad-scale oceanographic influences. However, all model validation tests, including of the combined model, determined strong interpolation but weak extrapolation capabilities. These results indicate that habitat use reflects both its availability and bird preferences, such that the realized distribution patterns differ for each population. The spatial predictions by the three SDMs were compared with tracking data and fishing effort to demonstrate the conservation pitfalls of extrapolating SDMs outside calibration regions. This exercise revealed that SDM predictions would have led to an underestimate of overlap with fishing effort and potentially misinformed bycatch mitigation efforts. Although SDMs can elucidate potential distribution patterns relative to large-scale climatic and oceanographic conditions, knowledge of local habitat availability and preferences is necessary to understand and successfully predict region-specific realized distribution patterns.


Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison.
Alcohol-related behaviors are moderately heritable and have ethnic-specific characteristics. At present, genetic studies for alcohol dependence (AD) in Chinese populations are underrepresented. We are the first to conduct a genome-wide association study (GWAS) for AD using 533 male alcoholics and 2848 controls of Han Chinese ethnicity and replicate our findings in 146 male alcoholics and 200 male controls. We then assessed genetic effects on AD characteristics (drinking volume/age onset/Michigan Alcoholism Screening Test (MAST)/Barratt Impulsiveness Scale (BIS-11)), and compared the polygenic risk of AD in Han Chinese with other populations (Thai, European American and African American). We found and validated two significant loci, one located in 4q23, with lead SNP rs2075633*ADH1B (Pdiscovery = 6.64 × 10-16) and functional SNP rs1229984*ADH1B (Pdiscovery = 3.93 × 10-13); and the other located in 12q24.12-12q24.13, with lead SNP rs11066001*BRAP (Pdiscovery = 1.63 × 10-9) and functional SNP rs671*ALDH2 (Pdiscovery = 3.44 × 10-9). ADH1B rs1229984 was associated with MAST, BIS_total score and average drinking volume. Polygenic risk scores from the Thai AD and European American AD GWAS were significantly associated with AD in Han Chinese, which were entirely due to the top two loci, however there was no significant prediction from African Americans. This is the first case-control AD GWAS in Han Chinese. Our findings demonstrate that these variants, which were highly linked with ALDH2 rs671 and ADH1B rs1229984, were significant modulators for AD in our Han Chinese cohort. A larger replication cohort is still needed to validate our findings.


Dynamic change of hydrogen sulfide during global cerebral ischemia-reperfusion and its effect in rats.
Hydrogen sulfide (H(2)S) is a gaseous messenger and serves as an important neuromodulator in central nervous system. In the current study, we investigated the change of H(2)S and cystathionine beta-synthase (CBS), an H(2)S-synthesizing enzyme at different time points of reperfusion following global cerebral ischemia in rats, and the effect of exogenous H(2)S on global cerebral ischemia-reperfusion injury. First, we used global cerebral ischemia-reperfusion model by occlusion of bilateral common carotid arteries and vertebral arteries. Next, we measured H(2)S levels in the hippocampus, cortex and plasma, the activity of H(2)S-synthesizing enzymes and expression of CBS mRNA and protein in the hippocampus and cortex at 12 h, 24 h, 48 h, 72 h and 7 days of reperfusion following 15 min cerebral ischemia. Second, we pretreated rats with different doses of sodium hydrogen sulfide (NaHS), an H(2)S donor and observed its effect on neuronal injury induced by 7 days of reperfusion after 15 min global cerebral ischemia. We found that when compared to sham group the amount of H(2)S in the hippocampus was increased significantly at 12 h of reperfusion after cerebral ischemia, markedly decreased at 24 h, restored to the same level as that in sham group at 48 h and maintained at 72 h and 7 days. The same change tendency in the levels of H(2)S was found in the cortex as described for the hippocampus. We found a similar change tendency in the activity of H(2)S-synthesizing enzymes, CBS mRNA and protein expression to that in the H(2)S level at different time points of reperfusion. Furthermore, while 180 micromol/kg NaHS pretreatment deteriorated the neuronal injury after global cerebral ischemia, 25 micromol/kg NaHS attenuated the neuronal injury. We suggest that a decrease of H(2)S level at 24 h of reperfusion after global cerebral ischemia may be involved in neuronal injury after cerebral ischemia and lower concentration rather than higher concentration of exogenous H(2)S may offer a protection against the neuronal injury induced by global cerebral ischemia-reperfusion.


Stability of stored histamine diphosphate solutions. Clinically useful information.
Histamine bronchoprovocation challenge has been shown to be extremely safe and useful as both a clinical diagnostic test and as a research tool in the study of bronchial asthma. Despite its widespread usage, information on the stability of histamine diphosphate (HDP) solutions has been lacking. We therefore studied the stability of HDP solutions as a function of time, concentration, fluorescent light exposure, and sterility. Our results indicated that HDP solutions between 2.76 and 22.10 mg/ml (histamine base, 1 to 8 mg/ml) show no evidence of degradation over a 4-month period when kept at 12 degrees C, unless gas sterilization techniques were used in preparing the solutions bacterial contamination was frequent, and at lower concentrations (i.e., between 0.08 and 0.28 mg/ml) HDP solutions that became contaminated with bacteria showed complete degradation within 9 to 11 wk of their preparation.


Multiple feeding vessels from left circumflex artery and right coronary artery to myxoma in left atrium.
A 62-year-old woman with six months history of dizziness was admitted to our hospital. A large mass in the left atrium was detected by transthoracic echocardiography. Coronary angiography showed two feeding arteries from the right coronary artery and left circumflex artery to the left atrium. Chest computed tomography, coronary computed tomographic angiography and contrast echocardiography were performed. Those showed multiple intratumoral neovascularities from surface of the mass. After those examinations, the mass was completely resected. Histopathologic examination confirmed the diagnosis of cardiac myxoma. There was no abnormal remnant mass, based on a follow-up transthoracic echocardiography.


Recurrent wheezing in infants: epidemiological changes.
To determine epidemiological changes in recurrent wheezing among infants in Curitiba, Brazil. This cross-sectional study used the questionnaire Estudio Internacional de Sibilancias en Lactantes (EISL). Parents of infants aged 12 to 15 months completed the instrument from August 2005 to December 2006 (phase I) and from September 2009 to September 2010 (phase III). Parents of 3,003 infants participated in phase I, and 22.6% of the infants had recurrent wheezing (≥ 3 episodes). After 5 years, 1,003 parents completed the same questionnaire during phase III, and 19.8% of the infants had recurrent wheezing (p = 0.1). There was a reduction in symptom severity (p = 0.001) and number of emergency department visits (p < 0.001), but not in number of hospitalizations (p = 0.12). Physician-diagnosed asthma was more frequent in phase III (p = 0.03). There were no changes in the prevalence of recurrent wheezing in infants, but there was an increase in physician-diagnosed asthma and a reduction in severity, which, however, did not affect the rate of hospitalizations.


Immunolocalization of mineralocorticoid receptor in human kidney, pancreas, salivary, mammary and sweat glands: a light and electron microscopic immunohistochemical study.
Using a polyclonal antibody against a synthetic fusion protein corresponding to 167 amino acids of the N-terminal region of the human renal mineralocorticoid receptor (MR), an immunohistochemical study was performed to investigate the intraglandular and intracellular localization of the receptor in human kidney, salivary gland, pancreas, mammary gland and sweat gland both at the light and electron microscopic levels. In the kidney, immunoreactivity was observed in distal convoluted tubules, branches of Henle's loop, and collecting tubules in the renal cortex, and papillary and Henle's loops' ducts in the renal medulla. No significant differences in the distribution of immunoreactivity were observed using different fixatives (10% neutral formalin, 100% methanol, 4% paraformaldehyde, PLP (periodate-lysine-2% paraformaldehyde) solution and Zamboni solution) and processing methods (paraffin embedding and frozen sectioning). Immunoreactivity in the kidney was observed in both the cytoplasm and nucleus, with cytoplasmic staining predominant, regardless of the methods of tissue preparation. Immunoelectron microscopy, employing a pre-embedding method, demonstrated the presence of immunoreaction precipitates in nuclei, endoplasmic reticulum, perinuclear cisternae, free cytoplasm and cell membranes. In nuclei, immunoreactivity was observed in euchromatin but not in heterochromatin, which is consistent with an association of MR with specific DNA regulatory elements located in transcriptionally active euchromatin. In other organs, MR was expressed in cells of the excretory ductal system where mineralocorticoids are known to play a role in electrolyte homeostasis.


Comparison between 3-Nitrooxyphenyl acetylsalicylate (NO-ASA) and O2-(acetylsalicyloxymethyl)-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (NONO-ASA) as safe anti-inflammatory, analgesic, antipyretic, antioxidant prodrugs.
Chronic inflammation is an underlying etiological factor in carcinogenesis; nonsteroidal anti-inflammatory drugs (NSAIDs) and their chemically modified NO-releasing prodrugs (NO-NSAIDs) are promising chemopreventive agents. The aim of this study was to conduct a head-to-head comparison between two NO-ASAs possessing different NO donor groups, an organic nitrate [3-nitrooxyphenyl acetylsalicylate (NO-ASA; NCX-4016)] and an N-diazeniumdiolate [NONO-ASA, O(2)- (acetylsalicyloxymethyl)-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (NONO-ASA; CVM-01)], as antiulcerogenic, analgesic, anti-inflammatory, and antipyretic agents. All drugs were administered orally at equimolar doses. For antiulcerogenic study, 6 h after administration, the number and size of hemorrhagic lesions in stomachs from euthanized animals were counted. Tissue samples were frozen for prostaglandin E(2) (PGE(2)), superoxide dismutase (SOD), and malondialdehyde determination. For anti-inflammatory study, 1 h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 6 h. For antipyretic study, 1 h after dosing, fever was induced by intraperitoneal LPS, and body core temperatures measured for 5 h. For analgesic study, time-dependent analgesic effect of prodrugs was evaluated by carrageenan-induced hyperalgesia. Drugs were administered 30 min after carrageenan. NO-ASA and NONO-ASA were equipotent as analgesic and anti-inflammatory agents but were better than aspirin. Despite a drastic reduction of PGE(2) in stomach tissue, both prodrugs were devoid of gastric side effects. Lipid peroxidation induced by aspirin was higher than that observed by prodrugs. SOD activity induced by both prodrugs was similar, but approximately 2-fold higher than that induced by aspirin. CVM-01 is as effective as NCX-4016 in anti-inflammatory, analgesic, and antipyretic assays in vivo, and it showed an equivalent safety profile in the stomach. These results underscore the use of N-diazeniumdiolate moieties in drug design.


A cross-sectional study of Salmonella in pork products in Chiang Mai, Thailand.
The occurrence of Salmonella in food of animal origin in Chiang Mai province was investigated by using a cross-sectional study during several phases of the pork production chain (cutting, transport, and retail) and of the environment in the cutting unit of a slaughterhouse. In total, 173 pork samples were obtained during the cutting phase, 173 samples from transported pork, 200 samples from retail products, and 300 samples from the slaughterhouse environment. Salmonella was detected in 55.5% of freshly cut pork, 70.5% of transported pork, and 34.5% of retail products. The five most prevalent Salmonella serotypes identified were Rissen (45.3%), Typhimurium (16.3%), Krefeld (10.6%), Stanley (6.3%), and Lagos (6.0%). Carcass contamination prior to cutting and in the slaughterhouse environment appeared to be important sources of Salmonella in transported pork and retail products. As Salmonella was also found during early stages of the slaughter process, attention should focus on all stages of the pork production chain to reduce contamination level and consumer risk of infection.


High-resolution surface-wave tomography from ambient seismic noise.
Cross-correlation of 1 month of ambient seismic noise recorded at USArray stations in California yields hundreds of short-period surface-wave group-speed measurements on interstation paths. We used these measurements to construct tomographic images of the principal geological units of California, with low-speed anomalies corresponding to the main sedimentary basins and high-speed anomalies corresponding to the igneous cores of the major mountain ranges. This method can improve the resolution and fidelity of crustal images obtained from surface-wave analyses.


Systolic blood pressure variability as a risk factor for stroke and cardiovascular mortality in the elderly hypertensive population.
To investigate whether baseline systolic blood pressure variability was a risk factor for stroke, cardiovascular mortality or cardiac events during the Syst-Eur trial. The Syst-Eur study was a randomized, double-blind, placebo-controlled trial, powered to detect differences in stroke rate between participants on active antihypertensive treatment and placebo. Systolic blood pressure variability measurements were made on 744 participants at the start of the trial. Systolic blood pressure variability was calculated over three time frames: 24 h, daytime and night-time. The placebo and active treatment subgroups were analysed separately using an intention-to-treat principle, adjusting for confounding factors using a multiple Cox regression model. An elderly hypertensive European population. Stroke, cardiac events (fatal and non-fatal heart failure, fatal and non-fatal myocardial infarction and sudden death) and cardiovascular mortality (death attributed to stroke, heart failure, myocardial infarction, sudden death, pulmonary embolus, peripheral vascular disease and aortic dissection). The risk of stroke increased by 80% (95% confidence interval: 17-176%) for every 5 mmHg increase in night-time systolic blood pressure variability in the placebo group. Risk of cardiovascular mortality and cardiac events was not significantly altered. Daytime variability readings did not predict outcome. Antihypertensive treatment did not affect systolic blood pressure variability over the median 4.4-year follow-up. In the placebo group, but not the active treatment group, increased night-time systolic blood pressure variability on admission to the Syst-Eur trial was an independent risk factor for stroke during the trial.


Why is it so hard to reach agreement on terminology? The case of developmental language disorder (DLD).
A recent project entitled CATALISE used the Delphi method to reach a consensus on terminology for unexplained language problems in children. 'Developmental language disorder' (DLD) was the term agreed by a panel of 57 experts. Here I reflect on points of difficulty that arose when attempting to reach a consensus, using qualitative information from comments made by panel members to illustrate the kinds of argument used. One issue of debate was the use of labels, in particular the term 'disorder', which was seen as having both pros and cons. The potential for labels to stigmatize or create low expectations was a particular concern. However, labels could also ensure language problems were not trivialized and could help avoid stigma by providing an explanation for behaviours that might otherwise meet with disapproval. Further debate surrounded issues of how best to identify cases of disorder. Although it was agreed there should be a focus on cases with a poor prognosis, it was recognized that our knowledge of factors related to prognosis was still incomplete. Furthermore, there was a tension between use of standardized tests, which allow for a relatively objective and reliable assessment of language, and more qualitative observations, which can capture functional aspects of communication that are not always picked up on formal assessment. Debate also surrounded the issue of the relationship between DLD and other conditions. Some favoured drawing a distinction between DLD and language disorders associated with other conditions, and others regarded such distinctions as unnecessary. We concluded that it was misleading to assume co-occurring conditions were causes of language disorder, but it was helpful to distinguish DLD from cases of language disorder associated with 'differentiating conditions' that had a known or likely biomedical origin, including brain injury, sensorineural hearing loss, genetic syndromes, intellectual disability and autism spectrum disorder. Furthermore, DLD could co-occur with milder neurodevelopmental disorders that did not have a clear biomedical aetiology. Normal-range non-verbal IQ has traditionally been incorporated in the diagnosis of DLD, but this was rejected as unsupported by evidence. DLD is a category that has utility in identifying children who would benefit from speech-language therapy services, but it should not be thought of as a well-defined condition. DLD has a multifactorial aetiology, is heterogeneous in terms of language features and overlaps with other neurodevelopmental disorders. Our notions of DLD are likely to be refined by further research into aetiology, associated characteristics and intervention effectiveness.


Examining Nonnormal Latent Variable Distributions for Non-Ignorable Missing Data.
Missing not at random (MNAR) modeling for non-ignorable missing responses usually assumes that the latent variable distribution is a bivariate normal distribution. Such an assumption is rarely verified and often employed as a standard in practice. Recent studies for "complete" item responses (i.e., no missing data) have shown that ignoring the nonnormal distribution of a unidimensional latent variable, especially skewed or bimodal, can yield biased estimates and misleading conclusion. However, dealing with the bivariate nonnormal latent variable distribution with present MNAR data has not been looked into. This article proposes to extend unidimensional empirical histogram and Davidian curve methods to simultaneously deal with nonnormal latent variable distribution and MNAR data. A simulation study is carried out to demonstrate the consequence of ignoring bivariate nonnormal distribution on parameter estimates, followed by an empirical analysis of "don't know" item responses. The results presented in this article show that examining the assumption of bivariate nonnormal latent variable distribution should be considered as a routine for MNAR data to minimize the impact of nonnormality on parameter estimates.


Gene and protein expressions and metabolomics exhibit activated redox signaling and wnt/β-catenin pathway are associated with metabolite dysfunction in patients with chronic kidney disease.
Changes in plasma concentration of small organic metabolites could be due to their altered production or urinary excretion and changes in their urine concentration may be due to the changes in their filtered load, tubular reabsorption, and/or altered urine volume. Therefore, these factors should be considered in interpretation of the changes observed in plasma or urine of the target metabolite(s). Fasting plasma and urine samples from 180 CKD patients and 120 age-matched healthy controls were determined by UPLC-HDMS-metabolomics and quantitative real-time RT-PCR techniques. Compared with healthy controls, patients with CKD showed activation of NF-κB and up-regulation of pro-inflammatory and pro-oxidant mRNA and protein expression as well as down-regulation of Nrf2-associated anti-oxidant gene mRNA and protein expression, accompanied by activated canonical Wnt/β-catenin signaling. 124 plasma and 128 urine metabolites were identified and 40 metabolites were significantly altered in both plasma and urine. Plasma concentration and urine excretion of 25 metabolites were distinctly different between CKD and controls. They were related to amino acid, methylamine, purine and lipid metabolisms. Logistic regression identified four plasma and five urine metabolites. Parts of them were good correlated with eGFR or serum creatinine. 5-Methoxytryptophan and homocystine and citrulline were good correlated with both eGFR and creatinine. Clinical factors were incorporated to establish predictive models. The enhanced metabolite model showed 5-methoxytryptophan, homocystine and citrulline have satisfactory accuracy, sensitivity and specificity for predictive CKD. The dysregulation of CKD was related to amino acid, methylamine, purine and lipid metabolisms. 5-methoxytryptophan, homocystine and citrulline could be considered as additional GFR-associated biomarker candidates and for indicating advanced renal injury. CKD caused dysregulation of the plasma and urine metabolome, activation of inflammatory/oxidative pathway and Wnt/β-catenin signaling and suppression of antioxidant pathway.


[Central arterial pressure and importance of its examinations in pulmonology].
Arterial pressure (AP) measured on brachial artery now cannot be considered as an unique marker of vascular tonus. According to literature data, more informative and prognostically valued parameters are central AP (CAP) and indices of arterial rigidity, which closer bound with hypertrophy of vascular wall, intensity of vascular atherosclerotic lesion and occurrence of cardiovascular complications, than peripheral AP and some other classic risk factors. Nevertheless, CAP measuring cannot be considered as alternative to classic method of AP measuring on brachial artery; it only supplements our view of concrete pathological process. Non-invasive CAP measuring at diseases of respiratory organs can be usable for more precise assessment of cardiovascular risk at chronic and acute forms of diseases of pulmonary organs (DPO). The highest risk of CAP increase and cardiovascular complications take place in patients with chronic obstructive pulmonary disease (COPD), aggravation of severe bronchial asthma and in hypertensive patients with pneumonia or aggravation of chronic DPO. Results of CAP measuring can be used as additional diagnostic criteria of stratification of DPO and their complications risk. Early diagnostics of CAP disturbances (aortal hyper- o hypotension) make possible to correct therapy and prevent unfavorable consequences of hemodynamic disturbances. Dynamic control of CAP is reasonable to use for correction of therapeutic programs in departments of intensive care.


Synaptic organization of septal projections in the rat medial habenula: a wheat germ agglutinin-horseradish peroxidase and immunohistochemical study.
The synaptic organization of septal inputs to the rat habenular complex of the dorsal diencephalon was examined employing the anterograde tracer wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). The cellular distribution of substance P (SP) and choline acetyltransferase (ChAT) immunoreactivity was also studied at the light and electron microscopic level. Following placements of tracer within the entire septum, labeled axons were observed in the stria medullaris and in the medial and lateral subnuclei of the habenula. Following injections of tracer in the nuclei triangularis and septofimbrialis of the posterior septum, the medial subnucleus was heavily labeled, whereas the lateral subnucleus was devoid of peroxidase activity. The medial subnucleus possessed labeled myelinated axons and terminals that contained clear, spherical vesicles and formed asymmetric contacts with dendritic spines and shafts. Terminals possessing WGA-HRP activity also formed non-synaptic junctions with other labeled or unlabeled terminals. SP and ChAT immunoreactivity in normal and colchicine-treated animals was confined to dendrites and somata within the medial habenula. Terminals containing clear spherical vesicles formed asymmetric synaptic contacts with these immunoreactive somatic and dendritic profiles. Based on the combined anterograde tracing and immunohistochemical data, it is proposed that septal projections provide a direct innervation to habenular neurons that contain ChAT or SP activity. These septal inputs may play an important role in the facilitation of the ChAT- and SP-positive habenular neurons, both of which provide prominent afferent inputs to the interpeduncular nucleus. Thus, neurons of the habenula and interpeduncular nucleus are under the direct and indirect influence of septal neurons within the limbic forebrain circuit.


Diagnostic and prognostic value of 99mTc-Tektrotyd scintigraphy and 18F-FDG PET/CT in a single-center cohort of neuroendocrine tumors.
The aim was to assess the diagnostic value of 99mTc-Tektrotyd scintigraphy (TCT) and positron emission tomography/computed tomography using F-18 fluorodeoxyglucose (18F-FDG PET/CT) in the detection and follow-up of neuroendocrine tumors (NETs), and their predictive value for disease progression. In this retrospective cohort, TCT and 18F-FDG PET/CT were performed in 90 patients (37 men, 53 women, mean age 52.7 ±15.1), with NET. Correlation of Ki67 and tumor grade versus Krenning score and SUVmax was assessed, Kaplan-Meier analysis was used for progression-free survival (PFS), and Cox regression analysis was performed to identify the association between progression-related factors and PFS. Out of 90, true positive TCT was detected in 56 (62.2%) patients, true negative in 19 (21.1%), false positive in 4 (4.4%), false negative in 11 (12.2%), while 18F-FDG PET/CT was true positive in 69 (76.7%) patients, true negative in 10 (11.1%), false positive in 5 (5.5%), false negative in 6 (6.7%). Mean 18F-FDG PET/CT SUVmax was 6.8 ±6.2. Diagnostic sensitivity of TCT was 83.6%, specificity 82.6%, accuracy 83.3% vs. 18F-FDG PET/CT sensitivity was 92.0%, specificity 66.7%, accuracy 87.8%. A significant correlation between Ki67 and SUVmax was found in positive 18F-FDG PET/CT findings, unlike the correlation between Ki67 and Krenning score. Median PFS was 25 months (95% CI: 18.2-31.8), in 18F-FDG PET/CT positive patients 23 months (95% CI: 16.3-29.7) and 18F-FDG PET/CT negative 26 months (p = 0.279). Progression-free survival predictors were SUVmax and Krenning score. In our study, TCT and 18F-FDG PET/CT have high diagnostic accuracy in detection of NET. Higher Krenning score on TCT and SUVmax in positive 18F-FDG PET/CT findings are predictors of disease progression. 99mTc-Tektrotyd scintigraphy and 18F-FDG PET/CT can be useful complementary tools in management of patients with NETs and in predicting patients' outcome.


Anaphylaxis in chopped guinea pig lung. I. Effect of peptidase substrates and inhibitors.
The quantitative release of histamine by specific antigen from perfused, chopped, sensitized guinea pig lung has been used to study the effect of peptidase substrates and inhibitors on the anaphylactic reaction. The anaphylactic release of histamine is prevented by chymotrypsin substrates and inhibitors but not by trypsin, carboxypeptidase, or leucine aminopeptidase substrates or the soybean trypsin inhibitor. The chymotrypsin substrates and inhibitors appear to be acting on an antigen-antibody-activated step because these substances fail to inhibit if the tissue is washed free of them prior to antigen addition, and because there is complete desensitization of the tissue without histamine release when the antigen is added in the presence of these inhibitors. The inhibitors work equally well in tissue from passively sensitized animals or in tissue from animals actively sensitized with either ovalbumin or bovine gamma globulin. These observations suggest that activation of a chymotrypsin-like enzyme is a necessary condition for the anaphylactic release of histamine in guinea pig lung. Diisopropylfluophosphate is inhibitory when present at the time of antigen addition but not when the tissue is washed free of unfixed diisopropylfluophosphate prior to adding antigen. This indicates that diisopropylfluophosphate must be acting exclusively on an enzyme which exists in lung tissue in a precursor form resistant to diisopropylfluophosphate until activated by the antigen-antibody interaction. Thiol alkylating or oxidizing agents also prevent the anaphylactic release of histamine, but in contrast to the situation with diisopropylfluophosphate and the other chymotrypsin inhibitors, the phase of the anaphylactic reaction inhibited by N-ethylmaleimide is available prior to the antigen-antibody interaction. The similarities and differences between immune hemolysis and anaphylaxis in chopped guinea pig lung are considered in detail.


S-antigen: preparation and characterization of site-specific monoclonal antibodies.
Previous attempts to prepare monoclonal antibodies (MAbs) against S-antigen, a photoreceptor cell protein involved in the visual process and a potent autoantigen for the induction of experimental autoimmune uveitis (EAU), have yielded MAbs which define only carboxyl terminal epitopes. In this study we devised alternate strategies to prepare five MAbs directed to other regions of the molecule. MAbC10C10 and MAbH11-A2 were prepared against synthetic peptides known to be uveitopathogenic and they were selected for more detailed studies. MAbC10C10 was generated against synthetic peptide BSA281-302 which contains a predictive consensus sequence for defined T cell epitopes (GIALD) as well as a consensus sequence for GTP-binding proteins. One human adenosine deaminase synthetic peptide containing an extensive amino acid sequence homology to BSA281-302 was a potent inhibitor of MAbC10C10 binding in a competitive inhibition radioimmunoassay. MAbH11-A2 was generated against peptide BSA303-332 which also contains a uveitopathogenic site. The binding site of MAbH11-A2 was determined to be within amino acid positions 305 to 314 (NLASSTIIKE) in S-antigen. This binding site corresponded closely to the binding site of an affinity-purified rat polyclonal antibody raised to human S-antigen. MAb5C6.47 was isolated from a mouse hyperimmunized with bovine S-antigen and was specific for a highly conserved sequence near the amino terminus, amino acid residues 42 to 48 (DGVVLVD). Both MAbC10C10 and MAb5C.47 were useful in screening gt11 cDNA libraries expressing S-antigen polypeptides as fusion proteins. Our results demonstrate the feasibility of producing site-specific MAbs potentially useful in the study of T cell-mediated immune mechanisms in EAU as well as in the phototransduction of vision.


The X chromosome and immune associated genes.
The X chromosome is known to contain the largest number of immune-related genes of the whole human genome. For this reason, X chromosome has recently become subject of great interest and attention and numerous studies have been aimed at understanding the role of genes on the X chromosome in triggering and maintaining the autoimmune aggression. Autoimmune diseases are indeed a growing heath burden affecting cumulatively up to 10% of the general population. It is intriguing that most X-linked primary immune deficiencies carry significant autoimmune manifestations, thus illustrating the critical role played by products of single gene located on the X chromosome in the onset, function and homeostasis of the immune system. Again, the plethora of autoimmune stigmata observed in patients with Turner syndrome, a disease due to the lack of one X chromosome or the presence of major X chromosome deletions, indicate that X-linked genes play a unique and major role in autoimmunity. There have been several reports on a role of X chromosome gene dosage through inactivation or duplication in women with autoimmune diseases, for example through a higher rate of circulating cells with a single X chromosome (i.e. with X monosomy). Finally, a challenge for researchers in the coming years will be to dissect the role for the large number of X-linked microRNAs from the perspective of autoimmune disease development. Taken together, X chromosome might well constitute the common trait of the susceptibility to autoimmune diseases, other than to explain the female preponderance of these conditions. This review will focus on the available evidence on X chromosome changes and discuss their potential implications and limitations.


Involvement of HSP70 and HO-1 in the protective effects of raloxifene on multiple organ dysfunction syndrome by endotoxemia in ovariectomized rats.
Accumulating evidence demonstrates that raloxifene, a selective estrogen receptor modulator, possesses anti-inflammatory action. This study evaluates the preventive effects of long-term treatment of raloxifene on acute inflammation and multiple organ dysfunction syndrome (MODS) in ovariectomized (OVX) rats with endotoxemia and its underlying mechanism of action. Adult female rats were OVX bilaterally to induce estrogen insufficiency. OVX rats were administered with raloxifene (1 mg/kg, gavage, once daily) for 8 weeks, beginning 1 week after surgery, followed by induction of sepsis via intravenous infusion of lipopolysaccharides (LPS; 30 mg/kg) for 4 hours. LPS-activated RAW 264.7 cells were used to investigate the mechanism of raloxifene. Ovariectomy amplified the endotoxemia-induced hypotensive effect, MODS, and superoxide anion production in the myocardium. The levels of inducible nitric oxide synthase, high mobility group box 1, and nuclear factor-κB p65 protein increased in OVX rats 6 hours after LPS initiation. Raloxifene mitigated MODS, together with reduced inducible nitric oxide synthase induction and fewer superoxide anions in organs. Raloxifene induced high levels of heat shock protein 70 (HSP70) and heme oxygenase 1 (HO-1), which are associated with an increase in the transcription factor heat shock factor-1 and Nrf-2, respectively. Pretreatment with quercetin, an inhibitor of HSP70, or SnPP, an inhibitor of HO-1, reversed the protective effects of raloxifene in septic OVX rats and LPS-activated macrophages. Long-term treatment with raloxifene reduces the severity of sepsis in OVX rats, attributed from up-regulation of HSP70 and HO-1 to exert the antioxidant and anti-inflammatory capacities. These findings provide new insights into bacterial infection during menopause and the molecular mechanism of raloxifene.


Intrauterine herpes simplex infection.
Neonatal herpes simplex virus (HSV) infection is usually acquired at birth. We present an infant with intrauterine HSV infection acquired after rupture of membranes. The infant was born prematurely to a woman with a first episode of genital herpetic infection in early pregnancy and rupture of membranes 11 days prior to delivery. The infant, at delivery had extensive brain damage, hemorrhage, and cystic encephalomalacia due to herpes infection. On 2nd day of life, Magnetic Resonance Imaging, suggested that the hemorrhage had occurred 7 to 14 days before the scan and the placental pathology was supportive of an ascending infection. The case of an ascending herpetic intrauterine infection after rupture of the membranes raises the question of prevention and suppressive antiviral therapy.


A role for Na+,K+-ATPase α1 in regulating Rab27a localisation on melanosomes.
The mechanism(s) by which Rab GTPases are specifically recruited to distinct intracellular membranes remains elusive. Here we used Rab27a localisation onto melanosomes as a model to investigate Rab targeting. We identified the α1 subunit of Na+,K+-ATPase (ATP1a1) as a novel Rab27a interacting protein in melanocytes and showed that this interaction is direct with the intracellular M4M5 loop of ATP1a1 and independent of nucleotide bound status of the Rab. Knockdown studies in melanocytes revealed that ATP1a1 plays an essential role in Rab27a-dependent melanosome transport. Specifically, expression of ATP1a1, like the Rab27a GDP/GTP exchange factor (Rab3GEP), is essential for targeting and activation of Rab27a to melanosomes. Finally, we showed that the ability of Rab27a mutants to target to melanosomes correlates with the efficiency of their interaction with ATP1a1. Altogether these studies point to a new role for ATP1a1 as a regulator of Rab27a targeting and activation.


Epizootiology of Sarcocystis infections in mule deer fawns in Oregon.
From 1974 to 1977, 62 wild mule deer (Odocoileus hemionus) fawns from Steens Mountain, Ore were euthanatized in autumn (23 deer), winter (21 deer), and spring (18 deer). The number of sarcocysts of Sarcocystis spp was counted in histologic sections of various muscular organs. Sarcocysts were seen in the muscle specimens of 14 of the 23 deer euthanatized in autumn (September to November) and in specimens from all 39 deer euthanatized in winter (December and January) and spring (March and April). The sarcocyst burden was greatest in the spring (736/deer), less in the winter (150/deer), and least in autumn (12/deer). Most sarcocysts collected from 3- to 5-month-old deer in autumn were immature, whereas most sarcocysts collected from 9- and 10-month-old deer in the spring were mature. More sarcocysts were seen in sections of muscles from limbs than in those of tongue, esophagus, and other skeletal muscles; the fewest sarcocysts were seen in the heart. Degenerating sarcocysts were seen in deer examined in the spring, but not in deer examined in autumn and winter. Sarcocystis was the only infectious agent found in unthrifty deer fawns. Of the 18 fawns (6 in autumn, 1974; 6 in winter, 1974; and 6 in spring, 1975) examined for helminths, only mild infections were seen in the deer examined in the spring of 1975. From 1974 to 1977, from the Crooked Creek area of Oregon, 48 mule deer fawns (12 in autumn, 18 in winter, and 18 in spring) were euthanatized and evaluated for Sarcocystis infections.(ABSTRACT TRUNCATED AT 250 WORDS)


Lung transplantation for patients with severe COVID-19.
Lung transplantation can potentially be a life-saving treatment for patients with nonresolving COVID-19-associated respiratory failure. Concerns limiting lung transplantation include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and the potential risk for allograft infection by pathogens causing ventilator-associated pneumonia in the native lung. Additionally, the native lung might recover, resulting in long-term outcomes preferable to those of transplant. Here, we report the results of lung transplantation in three patients with nonresolving COVID-19-associated respiratory failure. We performed single-molecule fluorescence in situ hybridization (smFISH) to detect both positive and negative strands of SARS-CoV-2 RNA in explanted lung tissue from the three patients and in additional control lung tissue samples. We conducted extracellular matrix imaging and single-cell RNA sequencing on explanted lung tissue from the three patients who underwent transplantation and on warm postmortem lung biopsies from two patients who had died from COVID-19-associated pneumonia. Lungs from these five patients with prolonged COVID-19 disease were free of SARS-CoV-2 as detected by smFISH, but pathology showed extensive evidence of injury and fibrosis that resembled end-stage pulmonary fibrosis. Using machine learning, we compared single-cell RNA sequencing data from the lungs of patients with late-stage COVID-19 to that from the lungs of patients with pulmonary fibrosis and identified similarities in gene expression across cell lineages. Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is their only option for survival.


Movement-induced modulation of soleus H reflexes with altered length of biarticular muscles.
Passive pedaling movements of the leg results in the phasic modulation of the soleus H reflex of that leg. In contrast, the H reflex of the contralateral leg is attenuated tonically. The phasic modulation of the reflex ipsilaterally can be attributed to the afferent discharge associated with the cyclic lengthening of the extensor muscles. We hypothesized that the tonic attenuation of the contralateral reflex could be explained if the afferent feedback arising from the lengthening of the biarticular muscles had an increased importance in regulating the amplitude of the contralateral reflex. To test this, the passive pedaling movements were reduced to those about either the knee or hip alone. Despite the alteration in the pattern of stretching of the biarticular muscles, the contralateral soleus H reflex was tonically attenuated during both forms of single joint movements. We suggest that the same phasic afferent discharge responsible for the modulation of the ipsilateral soleus H reflex initiates the tonic attenuation contralaterally, but that the signal undergoes a complex transformation in crossing the cord. These results do not rule out the possibility that the stretching of the biarticular muscles contributes to the attenuation of the ipsilateral soleus H reflex, which is subsequently masked by a powerful influence from the stretching of the uniarticular extensor muscles. To test this possibility, a second experiment manipulated the lengths of the muscles of the leg by altering the positions of the static joints during isolated rotation of either the knee or hip and measuring the amplitude of the ipsilateral soleus H reflex. From the results, it was clear that stretching the uniarticular extensor muscles produced the most dramatic effects. However, the stretch of the biarticular muscles yielded mild inhibitory influences if these muscles were near their maximal lengths.


Beliefs and attitudes towards complementary medicine among registered nurses in Hong Kong.
The personal use of and professional recommendation for complementary and alternative medicine (CAM) has been found to be related to nurses' knowledge and type of training background. Little, however, is known about CAM usage among nurses from Hong Kong who while of Chinese origin, are educated in western medical principles while exhibiting both folk knowledge and lay use of CAM in their daily lives. The purpose of this study was to investigate the beliefs and attitudes towards CAM in a population of Hong Kong registered nurses. A particular focus was the sources of CAM information and the nurse's professional communication exchanges about CAM usage. Cross-sectional survey. The survey was conducted from March to June 2006 with registered nurses (N=187) drawn form the Hong Kong College of Nursing. Nearly three quarters (71.9%) of the nurses agreed that CAM should be integrated into mainstream Western medicine. The majority (89.8%) of participants did not agree that CAM should not be taken when using Western medicine. The most common sources for the nurses surveyed to obtain CAM information were, in order of frequency, newspapers and magazines (64.2%), friends (57.2%) and books (43.9%). Approximately one in three (28.0-35.3%) participants had either sometimes or frequently initiated a discussion about CAM or a discussion about the interaction between CAM and Western medicine with nursing colleague. Consistently, nurses who had previously received training on CAM (48.9%) were also more likely to initiate CAM discussions than those who had not received such training (30.7%, p<0.05). More knowledge of CAM was in general, welcomed among nurses, with 93.6% of the nurses surveyed reporting an interest in further learning. A major recommendation is that HK registered nurses receive professional CAM training as a means to enhance patient care.


Crack Extension and Possibility of Debonding in Encapsulation-Based Self-Healing Materials.
The breakage of capsules upon crack propagation is crucial for achieving crack healing in encapsulation-based self-healing materials. A mesomechanical model was developed in this study to simulate the process of crack propagation in a matrix and the potential of debonding. The model used the extended finite element method (XFEM) combined with a cohesive zone model (CZM) in a two-dimensional (2D) configuration. The configuration consisted of an infinite matrix with an embedded crack and a capsule nearby, all subjected to a uniaxial remote tensile load. A parametric study was performed to investigate the effect of geometry, elastic parameters and fracture properties on the fracture response of the system. The results indicated that the effect of the capsule wall on the fracture behavior of the matrix is insignificant for tc/Rc ≤ 0.05. The matrix strength influenced the ultimate crack length, while the Young's modulus ratio Ec/Em only affected the rate of crack propagation. The potential for capsule breakage or debonding was dependent on the comparative strength between capsule and interface (Sc/Sint), provided the crack could reach the capsule. The critical value of Sc,cr/Sint,cr was obtained using this model for materials design.


A systematic approach to the reporting of medically relevant findings from whole genome sequencing.
The MedSeq Project is a randomized clinical trial developing approaches to assess the impact of integrating genome sequencing into clinical medicine. To facilitate the return of results of potential medical relevance to physicians and patients participating in the MedSeq Project, we sought to develop a reporting approach for the effective communication of such findings. Genome sequencing was performed on the Illumina HiSeq platform. Variants were filtered, interpreted, and validated according to methods developed by the Laboratory for Molecular Medicine and consistent with current professional guidelines. The GeneInsight software suite, which is integrated with the Partners HealthCare electronic health record, was used for variant curation, report drafting, and delivery. We developed a concise 5-6 page Genome Report (GR) featuring a single-page summary of results of potential medical relevance with additional pages containing structured variant, gene, and disease information along with supporting evidence for reported variants and brief descriptions of associated diseases and clinical implications. The GR is formatted to provide a succinct summary of genomic findings, enabling physicians to take appropriate steps for disease diagnosis, prevention, and management in their patients. Our experience highlights important considerations for the reporting of results of potential medical relevance and provides a framework for interpretation and reporting practices in clinical genome sequencing.


[Pediatric anesthesia and upper respiratory tract infections].
Surgery and anaesthesia of the respiratory ill children were in the past systematically postponed till complete disappearance of symptoms. We'll pay more attention about this. According to latest data children with upper respiratory tract infections are at increased risk for postoperative complications till 6 weeks after the disease. Respiratory events in these children are increased after general anaesthesia but there is little residual morbidity observed. Cancellation of the surgery involves important emotional, social and economic consequences for the child, his parents and the hospital. Any well defined consensus doesn't exist. The anaesthetic management of any children with upper respiratory tract infection is a real challenge and must be made on a case by case. We'll try to review some evidence-based guidelines for decision making in daily practise.


Effect of bariatric surgery on obstructive sleep apnea and hypopnea syndrome, electrocardiogram, and pulmonary arterial pressure.
We evaluated the impact of surgically-induced weight loss on Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS), electrocardiographic changes, pulmonary arterial pressure and daytime sleepiness in morbidly obese patients. 16 women and 13 men (n=29) underwent bariatric surgery in a 3-year period. The following tests were performed before and 1 year after surgery: nocturnal polysomnography, daytime Multiple Sleep Latency Test (MSLT), and echocardiogram. Mean age was 37.9+/-11 years (range 20-56). Preoperative body mass index was 56.5+/-12.3 kg/m(2) and it was 39.2+/-8.5 kg/m(2) at 13.7+/-6.6 months follow-up. Performed surgical procedures included: vertical banded gastroplasty in 6, Roux-en-Y gastric bypass in 12, and Distal Roux-en-Y gastric bypass in 11. Weight loss induced by surgery eliminated OSAHS in 46% of obese patients with an important improvement in oxygen saturation. Neck, thorax, waist and hip circumferences decreased significantly after surgical intervention but only neck circumference correlated significantly with the apnea/hypopnea index (Spearman rho=0.63, P <0.0001). Electrocardiographic abnormalities were present in 9 patients (31%) before surgery (sinus arrhythmia, ventricular arrhythmias, and sinus arrest). The number of electrocardiographic abnormalities decreased after surgery but new abnormalities appeared in some patients. Systolic pulmonary arterial pressure significantly decreased in the group of patients in whom OSAHS disappeared after surgery. Daytime sleepiness persisted after surgery in most patients. Bariatric surgery effectively reduces respiratory disturbances during sleep and improves pulmonary hypertension. Electro cardiographic abnormalities change after surgery. Daytime sleepiness appeared not to be related to respiratory disturbances during sleep.


Angiomyeloproliferative lesions following autologous stem cell therapy.
Some reports suggest that autologous hematopoietic stem cell transplantation holds potential for treatment of renal diseases such as lupus nephritis, but the safety of delivering various stem cell types (hematopoietic, mesenchymal, and endothelial precursors) is not well established. Here, we report a case of lupus nephritis treated by direct renal injection of autologous stem cells recovered from peripheral blood. The patient developed masses at the sites of injection and hematuria. We suspected transitional cell carcinoma but nephrectomy revealed that the masses were angiomyeloproliferative lesions. We believe that this previously undescribed pathologic entity is stem cell-derived or -induced. The biologic potential, including the neoplastic potential, of this lesion is unknown. This case illustrates that the development of angiomyeloproliferative lesions is a possible complication of stem cell therapy.


Exercise-Boosted Mitochondrial Remodeling in Parkinson's Disease.
Parkinson's disease (PD) is a movement disorder characterized by the progressive degeneration of dopaminergic neurons resulting in dopamine deficiency in the striatum. Given the estimated escalation in the number of people with PD in the coming decades, interventions aimed at minimizing morbidity and improving quality of life are crucial. Mitochondrial dysfunction and oxidative stress are intrinsic factors related to PD pathogenesis. Accumulating evidence suggests that patients with PD might benefit from various forms of exercise in diverse ways, from general health improvements to disease-specific effects and, potentially, disease-modifying effects. However, the signaling and mechanism connecting skeletal muscle-increased activity and brain remodeling are poorly elucidated. In this review, we describe skeletal muscle-brain crosstalk in PD, with a special focus on mitochondrial effects, proposing mitochondrial dysfunction as a linker in the muscle-brain axis in this neurodegenerative disease and as a promising therapeutic target. Moreover, we outline how exercise secretome can improve mitochondrial health and impact the nervous system to slow down PD progression. Understanding the regulation of the mitochondrial function by exercise in PD may be beneficial in defining interventions to delay the onset of this neurodegenerative disease.


Investigations into the possible effects of naturally occurring steroids on biosynthesis of 16-androstenes and androgens in microsomes of boar testis.
The possible interactions between naturally occurring steroids and three enzymes of the biosynthetic pathways of 16-androstenes and androgens in the boar testis were investigated. High concentrations (1 mmol/1) of several steroids reduced the production of 5,16-androstadien-3 beta-ol when a microsomal fraction of boar testis was incubated with pregnenolone at pH 7.0 (the pH optimum of this reaction was found to be 6.6). When some of these inhibitors were investigated in more detail using Lineweaver-Burk analyses, the apparent inhibition constants, Kv increased in value with increasing concentrations of inhibitors. When testosterone was added to 5,16-androstadien-3 beta-ol synthetase assays, the apparent Ki for 0.1 mumol testosterone/1 was 0.165 mumol/1 whereas those for 1.0, 10.0 and 100.0 mumol testosterone/1 were 1.65, 16.5 and 48.7 mumol/1 respectively. The apparent Michaelis constant, Km, of the reaction was 0.6 mumol/1. Similar results were obtained when oestrone, 17 alpha-hydroxyprogesterone and 4,16-androstadien-3-one were added as effectors. At physiological concentrations, these steroids would not affect the biosynthesis of 5,16-androstadien-3 beta-ol in vivo. Similarly, both 5 alpha-androst-16-en-3 beta-ol, quantitatively the most important 16-androstene in the boar testis and 5,16-androstadien-3 beta-ol were examined for their effects on the 17 alpha-hydroxy-C21-steroid, C-17,20 lyase (C-17,20 lyase) and 17 beta-hydroxysteroid dehydrogenase (17 beta-OHSDH) enzymes of androgen biosynthesis. Neither of these enzymes was affected by the 16-androstene steroids even at concentrations of 100 mumol/1, and the apparent Km values were 3.3 and 26.0 mumol/1 for C-17,20 lyase and 17 beta-OHSDH respectively. This lack of interaction between these pathways implies that the high levels of 16-androstene steroids produced by the testis will not interfere with androgen production, and also that the two side-chain cleavage steps from C21 precursors to C19 steroids are catalysed by independent systems.


Detection of subclinical skin manifestation in patients with psoriasis and psoriatic arthritis by fluorescence optical imaging.
To investigate the frequency of subclinical skin inflammation in both hands by fluorescence optical imaging (FOI) in patients with psoriasis/psoriatic arthritis (Pso/PsA) vs. rheumatoid arthritis (RA) and healthy individuals, and to correlate these findings with cardiovascular (CV) risk factors. The FOI scans were analyzed retrospectively to detect clinically invisible skin enhancement (0-3 scale) in both hands without relationship to underlying joints or blood vessels. We further characterized the FOI patterns and sorted the scans into groups based on the assumed diagnosis (Pso/PsA, RA, and healthy controls), which was compared with the physician's diagnosis. Furthermore, the associations between CV risk factors and imaging findings were investigated by regression analyses. We included FOI scans of patients with Pso/PsA (n = 80), RA (n = 78), and healthy controls (n = 25). Subclinical skin enhancement on the back of their hands was more common in Pso/PsA (72.5%) than in RA patients (20.5%) and healthy individuals (28.0%) (p < 0.001). Based on the FOI pattern, the majority of patients with Pso/PsA (72.5%), RA (76.9%), and healthy controls (68.0%) were classified correctly using the physician-based diagnosis as reference (overall agreement of 74%, kappa = 0.57). No CV risk factors except body weight (kg) were associated with subclinical skin enhancement (OR 1.04, 95% CI 1.02-1.06; p < 0.001). Subclinical subdermal skin inflammation was common in Pso/PsA patients using FOI. Based on the FOI pattern, most patients with Pso/PsA and were classified with the correct diagnosis. We demonstrated an important influence of the body weight on our FOI results. FOI may be a helpful novel tool to study microcirculation in rheumatic diseases with skin involvement.


Safety and efficacy of lansoprazole injection in upper gastrointestinal bleeding: a postmarketing surveillance conducted in Indonesia.
to assess the safety and effectiveness of lansoprazole injection (Prosogan®) in patients with upper gastrointestinal bleeding due to peptic ulcers or erosive gastritis. this study was a multicenter observational postmarketing study of lansoprazole (Prosogan®) injection. Patients with upper gastrointestinal bleeding due to peptic ulcers or erosive gastritis were given intravenous lansoprazole for a maximum of 7 days or until the bleeding stopped and the patients were able to take oral doses of lansoprazole. Primary outcome of the study was cessation of bleeding. Some laboratory parameters were also measured. among a total of 204 patients evaluable for safety, there was no adverse event reported during the study. A total of 200 patients were eligible for efficacy evaluation, 125 patients (62.5%) were males. Among these patients, upper GI bleeding stopped in 20 patients (10.0%) on day 1, in 71 patients (35.5%) on day 2, 75 patients (37.5%) on day 3, 24 patients (12.0%) on day 4, and 7 patients (3.5%) on day 5, making a cumulative of 197 patients (98.5%) on day 5. The hemostatic effect was rated as 'excellent' if the bleeding stopped within 3 days, and 'good' if the bleeding stopped within 5 days. Thus, the results were 'excellent' in 166 patients (83.0%) and 'good' in 31 patients (15.5%). These results were not different between males and females, between age below 60 years and 60 years and above, and between baseline Hb below 10 g/dL and 10 g/dL and above. the results of this observational postmarketing study in 200 patients with upper gastrointestinal bleeding due to peptic ulcers or erosive gastritis demonstrated that intravenous lansoprazole twice a day was well tolerated and highly effective.


Sequential interpenetrating polymer network hydrogel microspheres of poly(methacrylic acid) and poly(vinyl alcohol) for oral controlled drug delivery to intestine.
Sequential interpenetrating networks of poly(methacrylic acid) and poly(vinyl alcohol) have been prepared and cross-linked with glutaraldehyde to obtain pH sensitive microspheres by a water-in-oil emulsification method. Microspheres have been used to deliver the chosen model anti-inflammatory drug viz., ibuprofen to the intestine. Ibuprofen was encapsulated up to 70% within polymeric matrices. The interpenetrating polymer network formed was analysed by Fourier transform infrared spectroscopy. Differential scanning calorimetry and X-ray diffraction analyses were done on drug-loaded microspheres to confirm the polymorphism of ibuprofen. Results of this study indicated the molecular level dispersion of ibuprofen in the developed microspheres. Scanning electron microscopy confirmed the spherical nature and smooth surfaces of the microspheres produced. Mean particle size of the microspheres as measured by laser light scattering ranged between 51-176 microm. Swelling was performed in the simulated gastric as well as the intestinal conditions. Microspheres showed a pulsatile swelling behaviour when pH of the swelling media was altered. The swelling data have been fitted to an empirical equation to understand water transport trends as well as to calculate the diffusion coefficients. Values of diffusion coefficients in acidic media were lower than those found in the basic media. Values of diffusion coefficients decrease with increasing cross-linking of the matrix. In vitro release studies have been performed in 1.2 and 7.4 pH media to simulate the gastric and intestinal conditions. The in vitro release results indicated a dependence on the pH of the release media, extent of cross-linking and the amount of drug loading. The release data were fitted to an empirical relation to estimate the transport parameters and thereby to understand the transport mechanism.


An algorithm for the treatment of isolated zygomatico-orbital fractures.
To present algorithms for the treatment of zygomatico-orbital (ZMO) fractures and to review how many of our patients were treated using each. We have presented 2 algorithms: 1 for when intraoperative computed tomography (CT) scans are not available and 1 for when intraoperative CT scans are available. The data from all patients treated by us for isolated, unilateral ZMO fractures from January 1991 to December 31, 2013 with adequate medical records were retrospectively analyzed. The demographic information and treatment methods were collected and tabulated to determine how these patients' fractures had been classified using the 2 algorithms. Simple descriptive statistics were applied. A total of 883 patients with sufficient records who had undergone treatment of isolated, unilateral ZMO fractures were included. Of these 883 patients, 71 were classified as having high-energy ZMO fractures that had not been treated using 1 of the algorithms. A total of 758 patients with sufficient records to be included in the present study were treated using the algorithm before intraoperative CT scanning was available. Finally, 54 patients were treated using the algorithm after intraoperative CT scanning was available. The patients were similar demographically. The number of patients treated at each point in the algorithms is shown. Overall, only 40% of patients required internal orbital reconstruction. The treatment of most ZMO fractures can be sequential, using an algorithm to avoid unnecessary surgical approaches and procedures that can potentially cause iatrogenic deformities. The use of intraoperative CT scans will allow the surgeon to be less invasive, with greater predictability and precision.


The path to quit: how awareness of a large-scale mass-media smoking cessation campaign promotes quit attempts.
Although awareness of mass-media smoking cessation campaigns is hypothesized to affect quit behavior through changes in cessation-related attitudes, intentions, and motivation (cognitions), this has yet to be formally tested. Structural equation modeling was used to examine whether changes in cessation-related cognitions mediate the relationship between awareness of a national mass-media smoking cessation campaign, the EX campaign, and quit attempts in a cohort of 3,571 current smokers drawn from eight U.S. Designated Market Areas and followed over an approximate six-month period. Models were examined in the total sample and within racial/ethnic, gender, age, and educational strata. Data suggest that there are both a direct effect of confirmed awareness of EX on quit attempts as well as an indirect effect mediated by positive changes in cessation-related cognitions. Results are not uniform across subgroups; stratified analyses reveal that awareness of EX is significantly associated with positive changes in cessation-related cognitions and quit attempts only in Blacks, males, and those with less than a high-school education. Those developing health communication mass-media campaigns need to consider how media messages might differentially impact U.S. subpopulations in order to elicit desired behavioral change across target subgroups.


Routine portable chest radiographs in the medical intensive care unit: effects and costs.
To determine the effects and net costs of routine chest radiographs in a medical intensive care unit (ICU). A prospective, cohort study. A survey of experts in critical care and pulmonary diseases was undertaken to assess the effect of routine radiographs on patient management. Medical ICU of a university hospital. Eighty randomly selected patients admitted to a medical ICU. Two hundred fourteen experts were surveyed; 118 (55%)/214 responded. Daily interviews with medical ICU clinicians were conducted to assess the radiographic findings in the routine radiographs and actions taken based on these findings. Experts evaluated the findings, their importance, the actions taken, and the probability of complications if the actions had not been taken at that time. Experts also predicted increases in length of stay associated with these complications. Presence of radiographic findings, changes in management because of the findings, net costs of routine chest radiographs, cost per finding that prompted an action, and expected changes in length of stay resulting from the actions were also assessed. Seventy-two (33%) of 221 routine radiographs (95% confidence interval: 25% to 39%) had findings, of which 44 (61%) were judged important, and 18 (8%, 95% confidence interval: 5% to 12%) prompted actions. Experts predicted that each action averted, on average, 2.1 +/- 1.7 days (SD) in the medical ICU. Mean savings per routine radiograph was $98. Net savings from routine chest radiographs remained after sensitivity analysis for expected change in length of stay, percentage of patients with routine radiographs, and percentage of routine radiographs that produce changes in management. The policy of obtaining routine chest radiographs in the medical ICU is effective and results in net savings.


[DNA repair and tumour radiosensitivity: focus on ATM gene].
Numerous parameters influenced tumour radiosensitivity. The number of clonogenic cells, growth fraction, hypoxia and intrinsic radiosensitivity are among the most important determinants of radiocurability. Detection of DNA damage and repair pathways are important components of intrinsic radiosensitivity. ATM plays a major role in the cellular response to ionizing radiation: it induced DNA repair, cell cycle arrest, and apoptosis via induction of p53. Analysis of single nucleotide polymorphisms could help us to predict normal tissue sensitivity on an individual basis. Mutations of ATM is probably involved in some cases of severe radiation-induced late effects. Measure of residual double-strand breaks by immunochemistry of H2AX, but also ATM or MRE11, is another way to evaluate tumour radiosensitivity. Integration of genomics and functional approach are needed to better predict what the best candidates for a curative radiotherapy are.


Experimental and simulation-based investigation of He, Ne and Ar irradiation of polymers for ion microscopy.
Secondary ion mass spectrometry (SIMS) on the helium ion microscope (HIM) promises higher lateral resolution than on classical SIMS instruments. However, full advantage of this new technique can only be obtained when the interaction of He(+) or Ne(+) primary ions with the sample is fully controlled. In this work we investigate how He(+) and Ne(+) bombardment influences roughness formation and preferential sputtering for polymer samples and how they compare to Ar(+) primary ions used in classical SIMS by combining experimental techniques with Molecular Dynamics (MD) simulations and SD_TRIM_SP modelling. The results show that diffusion coefficients for He, Ne and Ar in polymers are sufficiently high to prevent any accumulation of rare gas atoms in the polymers which could lead to some swelling and bubble formation. Roughness formation was also not observed. Preferential sputtering is more of a problem, with enrichment of carbon up to surface concentrations above 80%. In general, the preferential sputtering is largely depending on the primary ion species and the impact energies. For He(+) bombardment, it is more of an issue for low keV impact energies and for the heavier primary ion species the preferential sputtering is sample dependent. For He(+) steady state conditions are reached for fluences much higher than 10(18) ions/cm(2). For Ne(+) and Ar(+), the transient regime extends up to fluences of 10(17)-10(18) ions/cm(2). Hence, preferential sputtering needs to be taken into account when interpreting images recorded under He(+) or Ne(+) bombardment on the HIM.


The 11beta-hydroxysteroid dehydrogenase enzymes--arbiters of the effects of glucocorticoids in synovium and bone.
Ever since the first use of cortisone, glucocorticoids have had a controversial role in the treatment of RA. There has been equally controversial research into the possible involvement of endogenous glucocorticoids, and their secretion via the hypothalamic-pituitary-adrenal (HPA) axis, in the development and persistence of inflammatory arthritis. Recently, our understanding of how glucocorticoids act has expanded substantially with the characterization of glucocorticoid-metabolizing enzymes that regulate glucocorticoid action at tissue level. These enzymes, the 11β-hydroxysteroid dehydrogenases, interconvert biologically inactive glucocorticoids such as cortisone and prednisone with their active counterparts, cortisol (hydrocortisone) and prednisolone. Without these enzymes, cortisone and prednisone would be therapeutically useless. Furthermore, in normal individuals, the activities of these enzymes influence the function of other components of the HPA axis. These enzymes are expressed in human synovial tissue and bone and have been implicated in the control of synovial inflammation, the development of periarticular bone loss and the sensitivity of bone to therapeutic glucocorticoids. This article reviews recent findings in this area that highlight the role of these enzymes in rheumatic diseases.


Mouse strain susceptibility to gonadectomy-induced adrenocortical tumor formation correlates with the expression of GATA-4 and luteinizing hormone receptor.
Certain inbred strains of mice, including DBA/2J, develop adrenocortical tumors in response to gonadectomy. Spindle-shaped cells with limited steroidogenic capacity, termed A cells, appear in the subcapsular region of the adrenal gland, followed by sex steroid-producing cells known as B cells. These changes result from unopposed gonadotropin production by the pituitary, but the adrenocortical factors involved in tumorigenesis have not been characterized. GATA-4, a transcription factor normally expressed in fetal, but not adult, adrenocortical cells, was found in neoplastic cells that proliferate in the adrenal cortex of gonadectomized DBA/2J mice. GATA-4 mRNA was detected in the adrenal glands of female mice 0.5 months after ovariectomy and reached a maximum by 4 months. Castrated male mice developed adrenocortical tumors more slowly than gonadectomized females, and the onset of GATA-4 expression in the adrenal was delayed. In situ hybridization and immunohistochemistry revealed GATA-4 mRNA and protein in A and B cells, but not in normal adrenocortical cells. mRNA encoding another factor associated with adrenocortical tumorigenesis, LH receptor (LHR), was detected in A and B cells. In addition, transcripts for P450 17 alpha-hydroxylase/C17-C20 lyase, an enzyme essential for the production of sex steroids, and inhibin-alpha were found in B cells. Unilateral ovarian regeneration, a phenomenon known to occur in gonadectomized mice, was observed in a subset of DBA/2J mice undergoing complete ovariectomy. In these animals, adrenocortical tumor progression was arrested; A cells and GATA-4 expression were evident, but there was no expression of LHR or P450 17 alpha-hydroxylase/C17-C20 lyase. Strain susceptibility to adrenocortical tumorigenesis (DBA/2J >> FVB/N) correlated with the expression of GATA-4 and LHR, implicating these factors in the process of adrenocortical neoplasia in response to continuous gonadotropin stimulation.


Identifying corals displaying aberrant behavior in Fiji's Lau Archipelago.
Given the numerous threats against Earth's coral reefs, there is an urgent need to develop means of assessing reef coral health on a proactive timescale. Molecular biomarkers may prove useful in this endeavor because their expression should theoretically undergo changes prior to visible signs of health decline, such as the breakdown of the coral-dinoflagellate (genus Symbiodinium) endosymbiosis. Herein 13 molecular- and physiological-scale biomarkers spanning both eukaryotic compartments of the anthozoan-Symbiodinium mutualism were assessed across 70 pocilloporid coral colonies sampled from reefs of Fiji's easternmost province, Lau. Eleven colonies were identified as outliers upon employment of a detection method based partially on the Mahalanobis distance; these corals were hypothesized to have been displaying aberrant sub-cellular behavior with respect to their gene expression signatures, as they were characterized not only by lower Symbiodinium densities, but also by higher levels of expression of several stress-targeted genes. Although these findings could suggest that the sampled colonies were physiologically compromised at the time of sampling, further studies are warranted to state conclusively whether these 11 scleractinian coral colonies are more stress-prone than nearby conspecifics that demonstrated statistically normal phenotypes.


Aetiologies of central nervous system infection in Viet Nam: a prospective provincial hospital-based descriptive surveillance study.
Infectious diseases of the central nervous system (CNS) remain common and life-threatening, especially in developing countries. Knowledge of the aetiological agents responsible for these infections is essential to guide empiric therapy and develop a rational public health policy. To date most data has come from patients admitted to tertiary referral hospitals in Asia and there is limited aetiological data at the provincial hospital level where most patients are seen. We conducted a prospective Provincial Hospital-based descriptive surveillance study in adults and children at thirteen hospitals in central and southern Viet Nam between August 2007-April 2010. The pathogens of CNS infection were confirmed in CSF and blood samples by using classical microbiology, molecular diagnostics and serology. We recruited 1241 patients with clinically suspected infection of the CNS. An aetiological agent was identified in 640/1241 (52%) of the patients. The most common pathogens were Streptococcus suis serotype 2 in patients older than 14 years of age (147/617, 24%) and Japanese encephalitis virus in patients less than 14 years old (142/624, 23%). Mycobacterium tuberculosis was confirmed in 34/617 (6%) adult patients and 11/624 (2%) paediatric patients. The acute case fatality rate (CFR) during hospital admission was 73/617 (12%) in adults and to 42/624 (7%) in children. Zoonotic bacterial and viral pathogens are the most common causes of CNS infection in adults and children in Viet Nam.


[Chronic anastomosis fistula: special problem in anastomosis wound healing].
Chronic anastomotic fistulas represent a complex clinical problem following various surgical gastrointestinal interventions. The etiology of anastomotic fistula includes multiple factors. Risk factors include patient- and surgery-dependent factors and those that are influenced by pre- and perioperative therapeutic measures. Therapeutic strategies include optimization of concomitant risk factors, medical strategies to improve wound healing, and endoscopical or surgical interventions.


A decision-analysis approach for contaminated dredged material management in South Korea.
To meet London Protocol requirements, South Korea is preparing to reduce the need for disposal of dredged material at sea. The new requirements controlling ocean disposal of dredged material pose significant challenges to the South Korean government, because the previous practice of offshore disposal of contaminated dredged material is no longer permitted. Hence, other alternatives for treating and disposing of contaminated dredged material are being evaluated and selected for implementation. A new management and decision approach is therefore needed for regulators and implementers to show what information and what decision-making processes were used to make the decision, to increase administrative transparency for such projects in the public domain. To address this need, an iterative approach was developed for dredged material management that includes the essential elements of process, people, and tools needed for successful environmental decision making. The approach has 6 steps: problem definition, developing objectives and criteria, identifying alternatives, performing the evaluation, comparing alternatives, and selecting the preferred alternative. The primary objective of the approach is to provide a systematic means of exploring contaminated dredged material management alternatives in South Korea using criteria that integrate risk with economic and stakeholder value information. The approach incorporates the desired decision-making attributes of transparency, comparative analysis, and inclusion of public input. Although it was developed for South Korea, the approach can be applied in any situation in which dredged material management alternatives are being considered to manage contaminated sediment risks.


Cetuximab-decorated and NIR-activated Nanoparticles Based on Platinum(IV)-prodrug: Preparation, Characterization and In-vitro Anticancer Activity in Epidermoid Carcinoma Cells.
Platinum-based drugs are the mainstay of chemotherapy regimens in a clinic, but their use is seriously limited by severe side effects and drug resistance. A cetuximab-decorated drug delivery system can selectively deliver drugs into EGFR-highexpressing cancer cells to prevent the shortcomings of platinum-based chemotherapy. Here, cetuximab-decorated and near-infrared (NIR)-activated nanoparticles based on Pt(IV)-prodrug (abbreviated as Cetuximab-Pt-INPs) was constructed. First, PEGylated Pt(IV)-prodrug was synthesized by a condensation reaction between c,c,t-[Pt(NH3)2Cl2(OOCCH2CH2COOH)(OH)] and MPEG-PLA. Then, Pt(IV)-prodrug and indocyanine green co-encapsulated nanoparticles (Pt-INPs) were prepared through an ultrasonic emulsification method. Finally, Cetuximab-Pt-INPs were obtained by decorating Pt-INPs with cetuximab as a targeting vector. The optimized Cetuximab-Pt-INPs exhibited a spherical core-shell shape of 138.5 ± 0.96 nm. In-vitro cellular uptake and cytotoxicity assays revealed that more Cetuximab-Pt-INPs with NIR irradiation were selectively taken up by A431 cells, thereby leading to higher cytotoxicity. These multifunctional nanoparticles may have promising potential for targeted and effective therapy against EGFR-highexpressing cells of epidermoid carcinoma.