Molecular Markers and Diagnostic Model Specific for Barrett's Esophagus.
Biomarkers involved in the progression of Barrett's esophagus (BE) have not been extensively studied. We aimed to identify novel molecular markers for the early diagnosis of BE. The expression profiles of GSE100843 including BE segment and normal squamous mucosa samples before and after vitamin D3 supplementation were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using the limma package. Principal component analysis was performed using Minitab, and DEGs in the top three principal components were clustered into different gene sets by the mclust package. Pathways and functions enriched by these gene sets were evaluated by deregulation score analysis. Key genes associated with BE were identified by coexpression analysis and a genetic algorithm. Using the xgboost package, an XGBoost classifier specific for BE was further constructed based on the key genes. A total of 2598 DEGs were identified, which were further clustered into nine gene sets. According to the deregulation scores of pathways and functions enriched by these gene sets, nine functional and pathway terms were significantly deregulated in BE. Among the DEGs, CREB3L1, HNF1B, and IL35 were genes with high fitness levels and connectivity degrees, predicting that they were key genes associated with BE. The XGBoost classifier constructed using the key genes was efficient and robust in BE prediction. The accuracies for prediction were 93% and 87% for training and validation datasets, respectively. Key genes may serve as novel biomarkers of BE, and the XGBoost classifier may contribute to the diagnosis of BE in future clinical practice.


[Observation of intraoperative lower limb blood flow of infrarenal aortic occlusion].
To summarize the surgical therapy and profiles of lower limb blood flow during surgery for chronic infrarenal aortic occlusion. A total of 36 patients of chronic infrarenal aortic occlusion underwent surgical procedures at our department from 2004 to 2011. Their clinical data were analyzed. Several methods were applied at different time points during surgery to observe the lower limb blood flow. SaO2, waveforms of dorsalis pedis artery and posterior tibial artery changed dramatically at different time points during surgery. Before and after blood occlusion, the SaO2 was 82% ± 6% and 23% ± 4% respectively, 1min after unclamped and after abdomen-closing, the SaO2 increased to 66% ± 5% and 88% ± 8% respectively. Doppler blood flow and blood oxygen saturation monitors are simple, non-invasive and objective detection methods for lower limb blood flow. A combination of both methods can improve the safety of surgery. Keeping the limbs warm and uses of spasmolytic drugs can facilitate the recovery of postoperative blood flow of lower limbs.


Efficacy of 0.5% Levofloxacin and 5.0% Povidone-Iodine Eyedrops in Reducing Conjunctival Bacterial Flora: Metagenomic Analysis.
Bacteria associated with postoperative endophthalmitis mostly originate from the normal bacterial flora of the patient's conjunctiva and eyelids, so the incidence of endophthalmitis may be reduced by eliminating the ocular and adnexal flora before surgery. We assessed the effectiveness of eyedrops of 0.5% levofloxacin and 5.0% povidone-iodine (PVI) in reducing conjunctival bacterial flora by metagenomic analysis. A total of 2.4 × 106 high-quality sequencing reads were generated from 93 conjunctival samples obtained from 31 eyes scheduled for cataract surgery before prophylactic therapy (group 1), after administration of 0.5% levofloxacin eyedrops into the conjunctival sac 8 times before surgery (group 2), and at 3 minutes after instillation of 5.0% PVI solution in the conjunctival sac (group 3) followed by surgery irrigation. The alpha diversity and beta diversity results demonstrated that group 3 had the least richness and biodiversity. Corynebacterium, Pseudomonas, Staphylococcus, Acinetobacter, and Streptococcus were predominant in all samples. The relative abundance of these bacterial species was 30.94%, 27.48%, 5.26%, 4.55%, and 2.61% in group 1, 16.32%, 44.10%, 2.19%, 5.39%, and 0.97% in group 2, and 5.90%, 65.55%, 0.39%, 5.36%, and 0.10% in group 3, respectively. The most easily and difficultly eliminated were Corynebacterium and Pseudomonas, respectively. In conclusion, the metagenomic analysis using high-throughput sequencing provides a scientific way for evaluating the effectiveness of a disinfection method from the perspective of analyzing the composition and diversity of the conjunctival microbiome. Despite the use of preoperative antisepsis regimens, the ocular surface of patients receiving cataract surgery could not be rendered completely aseptic, indicating that more strict disinfection methods need to be adopted to reduce the risk for anterior chamber contamination and endophthalmitis after cataract surgery.


Repression of genes involved in melanocyte differentiation in uveal melanoma.
Uveal melanoma (UM) has been the subject of intense interest due to its distinctive metastatic pattern, which involves hematogenous dissemination of cancerous cells toward the liver in 50% of patients. To search for new UM prognostic markers, the Suppressive Subtractive Hybridization (SSH) technique was used to isolate genes that are differentially expressed between UM primary tumors and normal uveal melanocytes (UVM). A subtracted cDNA library was prepared using cDNA from uncultured UM primary tumors and UVM. The expression level of selected genes was further validated by cDNA microarray, semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), and immunofluorescence analyses. One hundred-fifteen genes were identified using the SSH technique. Microarray analyses comparing the gene expression profiles of UM primary tumors to UVM validated a significant differential expression for 48% of these genes. The expression pattern of selected genes was then analyzed by semi-quantitative RT-PCR and was found to be consistent with the SSH and cDNA microarray findings. A down-regulation of genes associated with melanocyte differentiation was confirmed in UM primary tumors. Presence of undifferentiated cells in the UM was demonstrated by the expression of stem cell markers ATP-binding cassette sub-family G member 2 (ABCG2) and octamer-binding protein 4 (OCT4). We demonstrated that the SSH technique is efficient to detect differentially expressed genes between UM and UVM. The genes identified in this study represent valuable candidates for further functional analysis in UM and should be informative in studying the biology of this tumor. In addition, deregulation of the melanocyte differentiation pathway revealed the presence of UM cells exhibiting a stem cell-like phenotype.


Paramedic self-reported medication errors.
Continuing quality improvement (CQI) reviews reflect that medication administration errors occur in the prehospital setting. These include errors involving dose, medication, route, concentration, and treatment. A survey was given to paramedics in San Diego County. The survey tool was established based on previous literature reviews and questions developed based on previous CQI data. A total of 352 surveys were returned, with the paramedics reporting a mean of 8.5 years of field experience. They work an average of 11.0 shifts/month with an average shift length of 25.4 hours and 6.7 calls/shift. Thirty-two responding paramedics (9.1%) reported committing a medication error in the past 12 months. Types of errors included dose-related errors (63%), protocol errors (33%), wrong route errors (21%), and wrong medication errors (4%). Issues identified in contributing to the errors include failure to triple check, infrequent use of the medication, dosage calculation error, and incorrect dosage given. Fatigue, training, and equipment setup of the drug box were not listed as any of the contributing factors. The majority of these errors were self-reported to their CQI representative (79.1%), with 8.3% reported by the base hospital radio nurse, 8.3% found on chart review, and 4.2% noted by the paramedic during the call but never reported. Nine percent of paramedics responding to an anonymous survey reported medication errors in the past 12 months, with 4% of these errors never having been reported in the CQI process. Additional safeguards must continue to be implemented to decrease the incidence of medication errors.


Manganese utilization in the chick: effects of excess phosphorus on chicks fed manganese-deficient diets.
Young chicks were used in a 16-d feeding study to evaluate the effects of excess dietary P on Mn utilization. The basal casein-dextrose diet (1.4 mg Mn/kg) was supplemented with 0, 3.5, 7.0, or 10.5 mg Mn/kg from MnSO4.H2O and was fed in the absence or presence of .8% excess dietary P (equal P contributions from KH2PO4 and NaH2PO4). Diets containing .8% excess P were also supplemented with .8% excess Ca (CaCO3) to keep the Ca:P ratio above 1:25 so as to prevent anorexia associated with excess dietary P per se. Both growth rate and total tibia Mn responded linearly (P < .01) to Mn supplementation in chicks fed the normal level of P, but those fed excess P responded erratically. Excess P did not affect growth or tibia Mn in chicks fed the basal diet, but birds fed diets with supplemental inorganic Mn grew slower (P < .01) and had lower (P < .01) quantities of Mn in tibia when excess P was supplemented. Manganese content in the tibia of chicks fed excess P was 55% of that in chicks fed an adequate level of P.


Discovery of temperature-dependent, autoinductive reversal of enantioselectivity: palladium-mediated [3+3]-annulation of 4-hydroxycoumarins.
An unusual temperature-dependent autoinductive reversal of enantioselectivity (TARE) was discovered in an asymmetric palladium-mediated [3+3]-annulation of 4-hydroxycoumarin with Morita-Baylis-Hillman acetate. The absolute stereochemistry of the reaction product can be readily inversed by solely modifying the reaction temperature (from 10 °C to 60 °C), affording multicyclic adducts with the opposite configurations respectively in moderate to excellent enantiopurities. Furthermore, the first reported example of palladium-mediated bidirectional asymmetric autoinduction was identified to mainly contribute to the reversal of enantioselectivity, in which the corresponding adduct actively participated in the stereocontrol during the reaction. The correlation between reaction temperature and autoinduction was established, which might broaden the horizon of stereocontrol in asymmetric catalysis.


Theoretical model for motility and processivity of two-headed molecular motors.
The processive motion of two-headed molecular motors is studied theoretically by introducing a model that takes into account the coordinated motion of the constituent heads and the detachment process of heads from linear molecular tracks. The mean velocity, the mean run length, and the mean run time of the motor along the track are calculated numerically based on the Langevin equation. It turns out that the model, with appropriate choice of model parameters, can explain qualitatively the dependence of these quantities on the external load and adenosin triphosphate concentration observed experimentally for kinesin motors. Furthermore, we discuss how the motility and processivity of the motor are affected by various model parameters, which may be tested by experiments.


Invasive mucinous adenocarcinoma misdiagnosed as pneumonia: A case report.
Common imaging findings of invasive mucinous adenocarcinoma (IMA) include consolidation of the lung parenchyma, nodules, and ground-glass changes. However, the IMA imaging findings in the present case included diffuse, patchy and blurry density shadows through both lungs. To the best of the authors' knowledge, this image pattern has rarely been reported. The patient provided his consent and authorized the publication of photographs featuring his likeness. The present study reported a patient was diagnosed with IMA via pathologic and genetic analyses. Following antibiotic treatment, the lesions in both sides became larger. Further examinations were completed and IMA was confirmed by biopsy pathohistological examination. Pathological specimens were negative for almost all driver genes mutations, except KRAS. The patients and family refused further treatment, including chemotherapy, radiotherapy and interventional chemotherapy and the patient was discharged from The First Affiliated Hospital of Chengdu Medical College. The present case report emphasized that IMA should be suspected when imaging studies show diffuse lesions throughout both lungs. When a patient does not respond to treatment, clinicians should consider alternative diagnoses.


Low prevalence of Helicobacter pylori among symptomatic children from a hospital in Havana, Cuba.
The aims of this study were to assess the prevalence of Helicobacter pylori infection and to introduce a new algorithm to improve its diagnosis in Cuban symptomatic children. One hundred and thirty-three consecutive children with upper gastrointestinal symptoms were studied. Patients were endoscoped and antral biopsies were obtained for rapid urease test (RUT), culture and histology. Prevalence of H. pylori infection was 30.8%. No statistical differences were found concerning demographic, socio-economic factors or chief clinical complaints, between H. pylori-positive and negative children, except for haematemesis, which was significantly higher in infected children (p = 0.003). Histologically, there was statistical association between moderate chronic gastritis in infected children (p = 0.04). Culture and RUT had the highest specificity and sensitivity, respectively. The prevalence of H. pylori infection in Cuban symptomatic children is similar to the one observed in developed countries. Culture and RUT is a useful combination to diagnose H. pylori infection in paediatric patients.


Alcohol Use, HIV Treatment Adherence, and Sexual Risk Among People with a History of Injecting Drug Use in Vietnam.
Alcohol use can limit the effectiveness of antiretroviral therapy (ART) for people living with HIV (PLH) who have a history of injecting drug use. This study described the patterns of alcohol use among PLH with a history of injecting drug use in Vietnam and examined the relationships between alcohol use, adherence to ART, and sexual risks. We utilized cross-sectional data of 109 PLH on ART collected from a randomized controlled intervention trial in Vietnam. Approximately 30 and 46% of the participants were frequent and occasional drinkers, respectively. Frequent drinkers reported the highest number of missed medication days. About 61% of frequent drinkers reported having sex after using alcohol. Additionally, 23, 34, and 24% of nondrinkers, occasional drinkers, and frequent drinkers, respectively, reported inconsistent condom use during sex. Future intervention programs should address the issues of alcohol use and sexual risks to maximize the effectiveness of HIV treatment programs in Vietnam.


Anammox enrichment: impact of sludge retention time on nitrogen removal.
Enrichment of anammox bacteria has long been considered to be time-consuming because of the slow growth rate. This study evaluated the impact of sludge retention time (SRT) on the enrichment of anammox bacteria with a focus on nitrogen removal and specific anammox activity (SAA) in sequencing batch reactors (SBR). A total of eight different SRTs in the range of 30-1280 days at nitrogen loading rates (NLR) range from 12.1 to 122.1 mg/L-d were used to evaluate the anammox activity. SAA was negligible during the first 105 days due to denitrification and continued to increase thereafter to peak at 0.22 g N/g VSS-d on day 530 as the solids and hydraulic retention times (SRT and HRT) decreased from 120 to 80 days and 10 to 2 days, respectively. The stability of SAA (0.21 ± 0.02 g N/g VSS-d) from day 503 to day 670 indicates that anammox bacteria should be enriched at SRTs ranging from 30 to 80 days and NLR of 122.1 mg N/L-d. Moreover, the SBR achieved a maximum nitrogen removal efficiency of 86.6% at an SRT of 30 days and an NLR of 122 mg/L-d. Microbial analysis indicated that the two most abundant microorganisms accounting for 48% of the bacterial population are Anammoxoglobus followed by the heterotrophic denitrifier Rhizobiales. The maximum specific growth rate (was estimated as 0.062 d-1, consistent with typical of 0.057 d-1. The average first-order decay rate was estimated as 0.008 d-1, and the half-saturation constants (ks) averaged 16.2 mg NH4-N/L.


Validation of the Korean Migraine-Specific Quality of Life Questionnaire Version 2.1 in Episodic and Chronic Migraine.
To evaluate the validity of the Korean Migraine-Specific Quality of Life Questionnaire version 2.1 (K-MSQ v 2.1) in patients with episodic migraine (EM) or chronic migraine (CM). Subjects were recruited from a headache clinic and completed several self-report instruments, including the K-MSQ v 2.1, the Migraine Disability Assessment Scale (MIDAS), the Headache Impact Test-6 (HIT-6), the Migraine-Specific Quality of Life (MSQoL), the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7). Some of the subjects were assessed 4 weeks later and underwent the K-MSQ v 2.1 to examine test-retest reproducibility. Internal consistency and test-retest reproducibility were assessed to determine reliability. Construct validity was also assessed. Internal consistency (Cronbach's α) and test-retest reproducibility (intraclass correlation coefficients) were assessed to determine reliability. Pearson correlations were used to determine the validity. For the 180 eligible patients, the value of Cronbach's α for the three dimensions of the K-MSQ v. 2.1 (Role Function-Restrictive, Role Function-Preventive, and Emotional Function) were 0.954, 0.909, and 0.898, respectively, indicating excellent internal consistency. The intraclass correlation coefficients between baseline and the 4-week retest showed reliable reproducibility. The scores of the three dimensions for the K-MSQ v. 2.1 were well correlated with scores for the MIDAS, the HIT-6, the MSQoL, the PHQ-9, and the GAD-7. Internal consistency and construct validity showed similar tendencies in patients with EM and those with CM. The K-MSQ v 2.1 is a reliable and valid screening tool for evaluating QoL in patients with EM and CM.


[Not Available].
The health development in the Soviet Union is discussed in the various stages of socialist construction. The ideological and theoretical bases of Soviet medicine and public health policy are pointed out, and more particularly, the program and political documents of the Communist party in this field, laying emphasis on the motive forces of the development. The role played by Lenin for the organization and development of Soviet public health services and for the creation of its scientific theory is stressed.


Synergistic inhibition of T cell proliferation by gold sodium thiomalate and auranofin.
Gold compounds have been employed as therapeutic agents for rheumatoid arthritis (RA) for many years, but the molecular mechanism of their action is unknown. Our studies were undertaken to compare the immunosuppressive activities of parenteral gold (gold sodium thiomalate; GSTM) and orally active gold (auranofin; AF). The effects of GSTM and AF on in vitro models of human T cell activation were examined. GSTM and AF were found to exert a synergistic inhibitory effect on human T lymphocyte proliferation in vitro. The concentrations of GSTM and AF that synergistically inhibit T cell proliferation were easily attainable in the serum or synovium of patients treated with these agents. The synergistic inhibitory effect of GSTM and AF was not apparent when interleukin 2 (IL-2)R expression or IL-2 production was examined. The inhibitory effects of GSTM and AF could not be explained by a synergistic effect on proximal signal pathways. Our results demonstrate that GSTM and AF exert distinct effects on T cell responsiveness and together synergistically inhibit mitogen induced T cell proliferation. These results suggest the possibility that the combination of GSTM and AF may exert a heightened therapeutic effect in RA compared to the action of either agent alone.


A case of Streptococcus mitis endocarditis successfully treated by linezolid.
We report the successful treatment of infective endocarditis caused by Streptococcus mitis with linezolid in a patient with pre-existing valvular heart disease. The patient had multiple allergies to conventional antibiotics. Linezolid may provide an oral alternative in the treatment of infective endocarditis in patients with adverse drug reactions to traditional antibiotic regimens.


The US Food and Drug Administration's drug safety recommendations and long-acting beta2-agonist dispensing pattern changes in adult asthma patients: 2003-2012.
Emerging safety issues associated with long-acting beta2-agonist (LABA) have led to multiple regulatory activities by the US Food and Drug Administration (FDA) since 2003, including Drug Safety Communications (DSCs) in 2010. These DSCs had three specific recommendations for the safe use of LABA products in adult asthma treatment. We examined the initiation of LABA-containing products for adult asthma treatment using an intermittent time series approach in a claims database from 2003 to 2012. We assessed the alignment of dispensing patterns with the following 2010 FDA recommendations: 1) contraindicated use of single-ingredient (SI)-LABA without an asthma controller medication (ACM); 2) a LABA should only be used when asthma is not adequately controlled on inhaled corticosteroids (ICSs) or ACM; and 3) step-down asthma therapy (e.g., discontinue LABA) when asthma control is achieved. There were 477,922 adults (18-64 years old) dispensed a new LABA during 2003-2012. Among LABA initiators, patients who initiated an SI-LABA and who did "not" have an ACM dispensed on the same date decreased from >9% in 2003 (the initial labeling change) to <2% post 2010 DSCs (p-value <0.0001 in the segmented regression model). The proportion of asthma patients dispensed an ICS in 6 months prior to initiating LABA treatment did not increase. The proportion of patients with longer than 4 months of continuous treatment did not decrease over the study period. Although the decrease in SI-LABA initiation is consistent with FDA's recommendations, low ICS dispensing before initiating a LABA and LABA continuation practices require further efforts to move toward the recommended safe practices.


Epigenetic inheritance is unfaithful at intermediately methylated CpG sites.
DNA methylation at the CpG dinucleotide is considered a stable epigenetic mark due to its presumed long-term inheritance through clonal expansion. Here, we perform high-throughput bisulfite sequencing on clonally derived somatic cell lines to quantitatively measure methylation inheritance at the nucleotide level. We find that although DNA methylation is generally faithfully maintained at hypo- and hypermethylated sites, this is not the case at intermediately methylated CpGs. Low fidelity intermediate methylation is interspersed throughout the genome and within genes with no or low transcriptional activity, and is not coordinately maintained between neighbouring sites. We determine that the probabilistic changes that occur at intermediately methylated sites are likely due to DNMT1 rather than DNMT3A/3B activity. The observed lack of clonal inheritance at intermediately methylated sites challenges the current epigenetic inheritance model and has direct implications for both the functional relevance and general interpretability of DNA methylation as a stable epigenetic mark.


[Qualitative and quantitative determination of bacterial populations in aquatic habitats. 5. Comparison of 2 rapid sand filters].
The bacterial examinations of raw water and the effluent of two rapid sand filters showed differences with respect to the colony count, the identified species and the activity of the isolated bacteria. The raw waters of the treatment plants Si and Me are originated from an oligotrophic artificial lake and from ground-water respectively. The two raw waters contained only low numbers of bacteria, whereas the effluents of the filters showed a considerable increase of the bacterial counts. The results indicate a development of microbial populations in the filters. Furthermore there were also differences between the two filters examined. The first one led to the growth of Pseudomonas- and Flavobacterium species, the second one to Flavobacterium, Chromobacterium and Acinetobacter species. Comparing the raw water and the effluent, a reduction of special and total physiological activities of the isolated bacteria could be observed in filter I, whereas there wasn't any change in filter II.


Off-site repulsion-induced triplet superconductivity: a possibility for chiral p(x+y)-wave pairing in Sr2RuO4.
In order to probe the effect of charge fluctuations on triplet pairing, we study the pairing symmetry in the one-band Hubbard model having the off-site Coulomb repulsion (V) on top of the on-site repulsion as a model for the gamma band of Sr2RuO4, a strong candidate for a triplet pairing superconductor. The result, obtained with the dynamical cluster approximation combined with the quantum Monte Carlo method, and confirmed from the fluctuation exchange approximation, shows that while d(x(2)-y(2)) pairing dominates over p in the absence of V, introduction of V makes p(x+y) and d(xy) dominant. The gap function for the chiral p(x+y)+ip(x-y) has nodes that are consistent with the recent measurement of specific heat in rotated magnetic fields in the ruthenate. This suggests that the off-site repulsion may play an essential role in triplet superconductivity in this material.


Deciphering reproductive aging in women using a NOD/SCID mouse model for distinct physiological ovarian phenotypes.
Female fertility is negatively correlated with age, with noticeable declines in oocyte quantity and quality until menopause. To understand this physiological process and evaluate human approaches for treating age-related infertility, preclinical studies in appropriate animal models are needed. Thus, we aimed to characterize an immunodeficient physiological aging mouse model displaying ovarian characteristics of different stages during women's reproductive life. NOD/SCID mice of different ages (8-, 28-, and 36-40-week-old) were employed to mimic ovarian phenotypes of young, Advanced Maternal Age (AMA), and old women (~18-20-, ~36-38-, and >45-years-old, respectively). Mice were stimulated, mated, and sacrificed to recover oocytes and embryos. Then, ovarian reserve, follicular growth, ovarian stroma, mitochondrial dysfunction, and proteomic profiles were assessed. Age-matched C57BL/6 mice were employed to cross-validate the reproductive outcomes. The quantity and quality of oocytes were decreased in AMA and Old mice. These age-related effects associated spindle and chromosome abnormalities, along with decreased developmental competence to blastocyst stage. Old mice had less follicles, impaired follicle activation and growth, an ovarian stroma inconducive to growth, and increased mitochondrial dysfunctions. Proteomic analysis corroborated these histological findings. Based on that, NOD/SCID mice can be used to model different ovarian aging phenotypes and potentially test human anti-aging treatments.


Post-Pandemic: Investigation of the Degradation of Various Commercial Masks in the Marine Environment.
During COVID-19, personal protective equipment such as face masks was in urgent demand in the daily life. As the pandemic may have withdrawn from public attention, the disposal of face masks is a significant issue, especially plastic pollution. To address the degradation of the polymers in the marine environment, seven commercial masks were investigated via artificial weathering procedures in substitute ocean water. A suite of structural and chemical characterization techniques was employed, including scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, X-ray diffraction (XRD), and contact angle goniometry, to probe the treatment impact on commercially available N95, surgical, polyurethane, polyester, nylon, silk, and cotton masks. This work provides insights into the comprehensive analysis of material degradation in nature and raises public awareness of environmental issues post-pandemic.


Liver stiffness measurement by transient elastography predicts late posthepatectomy outcomes in patients undergoing resection for hepatocellular carcinoma.
Postoperative hepatic decompensation is a serious complication of liver resection in patients undergoing hepatectomy for hepatocellular carcinoma. Liver fibrosis and clinical significant portal hypertension are well-known risk factors for hepatic decompensation. Liver stiffness measurement is a noninvasive method of evaluating hepatic venous pressure gradient and functional hepatic reserve by estimating hepatic fibrosis. Effectiveness of liver stiffness measurement in predicting persistent postoperative hepatic decompensation has not been investigated. Consecutive patients with resectable hepatocellular carcinoma were recruited prospectively and liver stiffness measurement of nontumoral liver was measured using FibroScan. Hepatic venous pressure gradient was measured intraoperatively by direct puncture of portal vein and inferior vena cava. Hepatic venous pressure gradient ≥10 mm Hg was defined as clinically significant portal hypertension. Primary outcome was persistent hepatic decompensation defined as the presence of at least one of the following: unresolved ascites, jaundice, and/or encephalopathy >3 months after hepatectomy. One hundred and six hepatectomies, including 22 right hepatectomy (20.8%), 3 central hepatectomy (2.8%), 12 left hepatectomy (11.3%), 11 bisegmentectomy (10.4%), 30 unisegmentectomy (28.3%), and 28 partial hepatectomy (26.4%) were performed in patients for hepatocellular carcinoma (84 men and 22 women with median age of 67.5 years; median model for end-stage liver disease score of 8). Ninety-day mortality was 4.7%. Nine patients (8.5%) developed postoperative hepatic decompensation. Multivariate logistic regression bootstrapped at 1,000 identified liver stiffness measurement (P = .001) as the only preoperative predictor of postoperative hepatic decompensation. Area under receiver operating characteristic curve for liver stiffness measurement and hepatic venous pressure gradient was 0.81 (95% confidence interval, 0.506-0.907) and 0.71 (95% confidence interval, 0.646-0.917), respectively. Liver stiffness measurement ≥22 kPa had 42.9% sensitivity and 92.6% specificity and hepatic venous pressure gradient ≥10 mm Hg had 28.6% sensitivity and 96.3% specificity. In selected patients undergoing liver resection for hepatocellular carcinoma, transient elastography is an easy and effective test to predict persistent hepatic decompensation preoperatively.


Calcium pyrophosphate crystals in intermittent hydrarthrosis.
A 49-year-old female presented with intermittent hydrarthrosis affecting the right knee. Numerous calcium pyrophosphate crystals were demonstrated in synovial fluid aspirated from the knee.


Adipose-Derived Stem Cells Primed with Paclitaxel Inhibit Ovarian Cancer Spheroid Growth and Overcome Paclitaxel Resistance.
Adipose-derived stem cells (ADSCs) primed with paclitaxel (PTX) are now hypothesized to represent a potential Trojan horse to vehicle and deliver PTX into tumors. We analyzed the anticancer activity of PTX released by ADSCs primed with PTX (PTX-ADSCs) (~20 ng/mL) in a panel of ovarian cancer (OvCa) cells sensitive or resistant to PTX. We used two (2D) and three dimensional (3D) in vitro models (multicellular tumor spheroids, MCTSs, and heterospheroids) to mimic tumor growth in ascites. The coculture of OvCa cells with PTX-ADSCs inhibited cell viability in 2D models and in 3D heterospheroids (SKOV3-MCTSs plus PTX-ADSCs) and counteracted PTX-resistance in Kuramochi cells. The cytotoxic effects of free PTX and of equivalent amounts of PTX secreted in PTX-ADSC-conditioned medium (CM) were compared. PTX-ADSC-CM decreased OvCa cell proliferation, was more active than free PTX and counteracted PTX-resistance in Kuramochi cells (6.0-fold decrease in the IC50 values). Cells cultivated as 3D aggregated MCTSs were more resistant to PTX than 2D cultivation. PTX-ADSC-CM (equivalent-PTX) was more active than PTX in MCTSs and counteracted PTX-resistance in all cell lines. PTX-ADSC-CM also inhibited OvCa-MCTS dissemination on collagen-coated wells. In conclusion, PTX-ADSCs and PTX-MSCs-CM may represent a new option with which to overcome PTX-resistance in OvCa.


The effect of intraportal prostaglandin E1 on adhesion molecule expression, inflammatory modulator function, and histology in canine hepatic ischemia/reperfusion injury.
Prostaglandin E1 (PGE1) is known to protect the liver from I/R, however, the mechanism of cytoprotection is not well understood. This study investigates the effect of intraportal infusion of PGE1 in a warm liver ischemia/reperfusion (I/R) model on cytokines, adhesion molecules and liver structure. Twenty dogs underwent laparotomy under general anesthesia. PGE1 (0.02 microg\kg\min) was perfused through the portal vein in the PGE1 group (n = 10), or a similar volume of Ringer's solution in the control group (n = 10) for 15 min. Liver ischemia was induced by hepatic artery and portal vein occlusion and PGE1 was infused via the portal vein for 60 min. The occlusion was released and PGE1 infusion recommenced for 30 min. Blood and liver biopsies were sampled at baseline, 60 min ischemia, and 30 min reperfusion and assessed for transaminases, cytokines, adhesion molecules, and electron microscopy. PGE1 infusion significantly reduced transaminases TNF-alpha, sICAM-1, sP-selectin, and sE-selectin on ischemia and reperfusion. PGE1 reduced hepatocytic degeneration, portal and central ICAM-1 expression, central and sinusoidal VCAM-1 expression, portal and central P-selectin expression, and portal and sinusoidal E-selectin expression on reperfusion. Intraportal PGE1 infusion reduced I/R injury and was associated with down-regulation of ICAM-1, VCAM-1, P-selectin, and E-selectin on reperfusion.


Evaluation of antibiotic effects on Pseudomonas aeruginosa biofilm using Raman spectroscopy and multivariate analysis.
We investigate the mode of action and classification of antibiotic agents (ceftazidime, patulin, and epigallocatechin gallate; EGCG) on Pseudomonas aeruginosa (P. aeruginosa) biofilm using Raman spectroscopy with multivariate analysis, including support vector machine (SVM) and principal component analysis (PCA). This method allows for quantitative, label-free, non-invasive and rapid monitoring of biochemical changes in complex biofilm matrices with high sensitivity and specificity. In this study, the biofilms were grown and treated with various agents in the microfluidic device, and then transferred onto gold-coated substrates for Raman measurement. Here, we show changes in biochemical properties, and this technology can be used to distinguish between changes induced in P. aeruginosa biofilms using three antibiotic agents. The Raman band intensities associated with DNA and proteins were decreased, compared to control biofilms, when the biofilms were treated with antibiotics. Unlike with exposure to ceftazidime and patulin, the Raman spectrum of biofilms exposed to EGCG showed a shift in the spectral position of the CH deformation stretch band from 1313 cm(-1) to 1333 cm(-1), and there was no difference in the band intensity at 1530 cm(-1) (C = C stretching, carotenoids). The PCA-SVM analysis results show that antibiotic-treated biofilms can be detected with high sensitivity of 93.33%, a specificity of 100% and an accuracy of 98.33%. This method also discriminated the three antibiotic agents based on the cellular biochemical and structural changes induced by antibiotics with high sensitivity and specificity of 100%. This study suggests that Raman spectroscopy with PCA-SVM is potentially useful for the rapid identification and classification of clinically-relevant antibiotics of bacteria biofilm. Furthermore, this method could be a powerful approach for the development and screening of new antibiotics.


Effect of commercial processing of canola and rapeseed on growth of larvae of the yellow mealworm, Tenebrio molitor L.
Larvae of Tenebrio molitor L., Gembloux strain, race F, were used to determine the nutritional quality of commercial canola and rapeseed products. Application of heat in commercial processing increased considerably the nutritive values of Midas, Tower and Torch cultivars, and to a lesser extent that of Candle. This improvement was most noticeable for thigh-glucosinolate cultivars, presumably through the destruction of a mechanism for production of isothiocyanates that may be phagodeterrent or toxic to the larvae. For low-glucosinolate varieties, the improvement may be related to inhibition of nitrile production in heated material. The processing also reduced the concentration of available lysine in the products of all four cultivars; however, growth was unimpaired by this reduction. The latter results suggest that the feed products resulting from processing may exceed the optimal dietary requirement of lysine by larvae of Tenebrio molitor.


Development of Overarm Throwing Technique Reflects Throwing Ability during Childhood.
It is important to acquire fundamental movement skills during childhood. Throwing is a representative manipulative skill required for various intrinsic factors. However, the relationship between intrinsic factors and throwing ability in childhood is unclear. The purpose of this study was to investigate intrinsic factors related to the ball throwing distance of Japanese elementary school children. Japanese elementary school children from grades 1-6 (aged 6-12 years; n=112) participated in this study. The main outcome was throwing ability, which was measured as the ball throwing distance. We measured five general anthropometric parameters, seven physical fitness parameters, and the Roberton's developmental sequence for all subjects. The relationships between the throwing ability and the 13 parameters were analysed. The Roberton's developmental sequence was the best predictor of ball throwing distance (r=0.80, p≤0.01). The best multiple regression model, which included sex, handgrip strength, shuttle run test, and the Roberton's developmental sequence, accounted for 81% of the total variance. The development of correct throwing technique reflects throwing abilities in childhood. In addition to the throwing sequence, enhancement of grip strength and aerobic capacity are also required for children's throwing ability.


Caffeic acid treatment alters the extracellular adenine nucleotide hydrolysis in platelets and lymphocytes of adult rats.
This study evaluated the effects of caffeic acid on ectonucleotidase activities such as NTPDase (nucleoside triphosphate diphosphohydrolase), Ecto-NPP (nucleotide pyrophosphatase/phosphodiesterase), 5'-nucleotidase and adenosine deaminase (ADA) in platelets and lymphocytes of rats, as well as in the profile of platelet aggregation. Animals were divided into five groups: I (control); II (oil); III (caffeic acid 10 mg/kg); IV (caffeic acid 50 mg/kg); and V (caffeic acid 100 mg/kg). Animals were treated with caffeic acid diluted in oil for 30 days. In platelets, caffeic acid decreased the ATP hydrolysis and increased ADP hydrolysis in groups III, IV and V when compared to control (P<0.05). The 5'-nucleotidase activity was decreased, while E-NPP and ADA activities were increased in platelets of rats of groups III, IV and V (P<0.05). Caffeic acid reduced significantly the platelet aggregation in the animals of groups III, IV and V in relation to group I (P<0.05). In lymphocytes, the NTPDase and ADA activities were increased in all groups treated with caffeic acid when compared to control (P<0.05). These findings demonstrated that the enzymes were altered in tissues by caffeic acid and this compound decreased the platelet aggregation suggesting that caffeic acid should be considered a potentially therapeutic agent in disorders related to the purinergic system.


In Situ Atomic-Scale Observation of Electrochemical Delithiation Induced Structure Evolution of LiCoO2 Cathode in a Working All-Solid-State Battery.
We report a method for in situ atomic-scale observation of electrochemical delithiation in a working all-solid-state battery using a state-of-the-art chip based in situ transmission electron microscopy (TEM) holder and focused ion beam milling to prepare an all-solid-state lithium-ion battery sample. A battery consisting of LiCoO2 cathode, LLZO solid state electrolyte and gold anode was constructed, delithiated and observed in an aberration corrected scanning transmission electron microscope at atomic scale. We found that the pristine single crystal LiCoO2 became nanosized polycrystal connected by coherent twin boundaries and antiphase domain boundaries after high voltage delithiation. This is different from liquid electrolyte batteries, where a series of phase transitions take place at LiCoO2 cathode during delithiation. Both grain boundaries become more energy favorable along with extraction of lithium ions through theoretical calculation. We also proposed a lithium migration pathway before and after polycrystallization. This new methodology could stimulate atomic scale in situ scanning/TEM studies of battery materials and provide important mechanistic insight for designing better all-solid-state battery.


Role of ornithine decarboxylase in repair of gastric mucosal stress ulcers.
The purpose of this study was to determine whether ornithine decarboxylase (ODC) has a role in mucosal repair during the first 24 h after stress-induced damage. Rats were fasted 22 h, placed in a restraint cage, and immersed in water to the xiphoid process for 6 h. Animals were killed either immediately after the period of stress or at 2-h intervals up to 24 h thereafter. Gastric mucosal ODC increased significantly from 0 to 12 h and peaked 4 h after the 6-h stress period. By 24 h enzyme activity in the gastric mucosa was near normal. Macroscopic lesions were regularly produced after 6 h of stress. Histologically, stress caused extensive damage to the superficial epithelial cells, extending in some cases into the mucosa and beyond the basal lamina. However, after stress the mucosa recovered quickly, returning to near normal 24 h later. The decreases in mucosal content of DNA, RNA, and protein caused by stress also were restored and reached near-normal levels 24 h after stress. alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ODC, not only inhibited the ODC activity but significantly delayed the recovery from injury as well. DFMO also prevented the restoration of DNA, RNA, and protein content of the gastric mucosa. In conclusion, stress-induced gastric mucosal lesions are accompanied by significant increases in ODC activity. The increased ODC is necessary for the normal repair of the mucosa.


Congenital Volkmann ischemic contracture: a case report.
Congenital Volkmann ischemic contracture is a rare condition in which a neonate presents with an ulcerated forearm, necrotic subcutaneous tissue, nerve palsy, and muscular necrosis. We report a case of a 1-day-old infant who presented with an ulceration of the left forearm noted at delivery combined with decreased motor function of the left distal forearm. Histologic examination of the ulceration revealed findings of subcutaneous fat necrosis of the newborn. To our knowledge, this is the first case for which the findings of subcutaneous fat necrosis have been seen histologically.


Agomelatine: a new option for treatment of depression?
A number of diverse antidepressants with different mechanisms of action are available today. However, the mechanisms of action of US FDA-approved antidepressants still mainly rely on targeting monoamine neurotransmitters. The inadequate remission and response rates achieved by antidepressant treatment for depression have been well known through a number of manufacturer-sponsored randomized, placebo-controlled, clinical trials (RCTs), independent RCTs, some large practical clinical trials and many meta-analyses. In the light of the limited efficacy of currently available antidepressants and the need for an antidepressant with a novel mechanism of action, the availability of agomelatine is prudent and timely for clinical practice. Although agomelatine has been approved for the treatment of depression in Europe and some other countries, its clear efficacy has been questionable based on results from individual RCTs and meta-analyses. However, agomelatine may be more beneficial in specific populations such as those who suffer from unwanted adverse events (AEs) (i.e., sexual dysfunction) by current antidepressants or elderly populations who are vulnerable to AEs. Based on currently available findings, agomelatine may not be recommendable as the first-line antidepressant for treating depression; especially, its putative benefits compared with other antidepressants must be thoroughly studied in adequately powered and well-designed future clinical trials.


Rapid separation of enkephalins and endorphins on Sep-Pak reverse phase cartridges.
A simple, rapid method is described for separating neuropeptides. Samples were injected on Sep-Pak disposable reverse phase cartridges and eluted with a step gradient of n-propanol in formate-pyridine buffer. Enkephalins are separated from metabolic products. Separation alpha, beta and gamma-endorphin demonstrated, and Met- and Leu-enkephalin are also separated. This inexpensive, reproducible method a useful in studies of neuropeptide metabolism, purification of synthesized peptides, separation prior to RIA, or concentration of neuropeptides.


[Whole-skin electron therapy: a therapeutic concept for mycosis fungoides and Sézary syndrome. 2: Therapy].
The alterations of mycosis fungoides of a malignant T-cell lymphoma are extremely radiosensitive. In the treatment of the cutaneous manifestation of mycosis fungoides, the whole-skin electron therapy is superior to the superficial application of mechlorethamine (NH2), to photochemotherapy with psoralen and ultraviolet radiation as well as to chemotherapy as monotherapy and combined therapy. Complete remissions are to be expected in 93% of all cases after application of a high total dose of more than 30 Gy. After less than 10 Gy, this rate is 18%. A combination of whole-skin electron therapy (30 Gy) with chemotherapy or with a total lymphoid irradiation with 30 Gy represents a new approach for the treatment of advanced tumor stages.


An ultrasensitive multi-walled carbon nanotube-platinum-luminol nanocomposite-based electrochemiluminescence immunosensor.
An ultrasensitive electrochemiluminescence (ECL) immunosensor for carbohydrate antigen 19-9 (CA19-9) detection using multi-walled carbon nanotube-platinum-luminol nanocomposites (MWCNT-Pt-luminol) as nanointerface and signal tags was designed. First, the MWCNT-Pt-luminol nanocomposite was decorated on the surface of a glassy carbon electrode (GCE) through the film-forming properties of chitosan (Chi). Then, the CA19-9 antibody (anti-CA19-9) was attached to the modified electrode surface via crosslinking with glutaraldehyde (GA). When CA19-9 was captured by its antibody immobilized on the immune platform via immunoreaction, the ECL signal intensity decreased. Under optimal conditions, the proposed ECL immunosensor showed excellent performance for CA19-9 ranging from 0.0001 U mL-1 to 10.0 U mL-1, with a detection limit of 0.000046 U mL-1 (S/N = 3) and a correlation coefficient of R = 0.9980. This is attributed to the fact that the MWCNTs-Pt nanomaterial has excellent conductivity and it could facilitate the decomposition of H2O2 to generate various reactive oxygen species (ROSs); thus, the ECL signals of luminol were effectively amplified and the sensitivity of the sensor was greatly increased. The prepared ECL immunosensor displayed simple, fast analysis, excellent stability, good reproducibility, and high specificity. Moreover, the developed ECL immunosensor provided satisfactory results in the determination of CA19-9 in real human serum samples.


Antibiotic overuse for acute respiratory tract infections in Sri Lanka: a qualitative study of outpatients and their physicians.
Acute respiratory tract infections (ARTIs) are a common reason for antibiotic overuse worldwide. We previously showed that over 80% of outpatients presenting to a tertiary care hospital in Sri Lanka with influenza-like illness received antibiotic prescriptions, although almost half were later confirmed to have influenza. The purpose of this qualitative study was to assess Sri Lankan patients' and physicians' attitudes towards ARTI diagnosis and treatment. Semi-structured interviews were conducted with 50 outpatients with ARTIs and five physicians in the Outpatient Department (OPD) at a large, public tertiary care hospital in southern Sri Lanka. Interviews were audio-recorded, transcribed, and analyzed for themes related to ARTI diagnosis and treatment. Patients frequently sought ARTI care in the public sector due to the receipt of free care and the perception that government hospitals carried a sense of responsibility for patients' health. Patients reported multiple medical visits for their illnesses of short duration and many indicated that they were seeking care in the OPD while at the hospital for another reason. While patients generally expected to receive medication prescriptions at their visit, most patients were not specifically seeking an antibiotic prescription. However, more than 70% of patients received antibiotic prescriptions at their OPD visit. Physicians incorrectly perceived that patients desired antibiotics or "capsules," a common formulation of antibiotics dispensed in this outpatient setting, and cited patient demand as an important cause of antibiotic overuse. Physicians also indicated that high patient volume and fear of bacterial superinfection drove antibiotic overuse. Patients in this study were seeking medication prescriptions for their ARTIs, but physicians incorrectly perceived that antibiotic prescriptions were desired. High patient volume and fear of bacterial superinfection were also important factors in antibiotic overuse. Training of physicians regarding guideline-concordant management and dealing with diagnostic uncertainty, education of patients regarding ARTI etiology and management, and systematic changes in the public outpatient care structure may help decrease unnecessary antibiotic prescriptions for ARTIs in this setting.


Evolution and transmission patterns of extensively drug-resistant tuberculosis in China.
The emergence and transmission of extensively drug-resistant tuberculosis (XDR-TB) pose an increasing threat to global TB control. This study aimed to identify the patterns of evolution and transmission dynamics of XDR-TB in populations in a region of China where TB is highly endemic. We analyzed a total of 95 XDR-TB isolates collected from 2003 to 2009 in Chongqing, China. Eight drug resistance genes covering 7 drugs that define XDR-TB were amplified by PCR followed by DNA sequencing. Variable-number tandem repeat 16-locus (VNTR-16) genotyping and genotypic drug resistance profiles were used to determine the evolution or transmission patterns of XDR-TB strains. Our results indicated that the Beijing genotype was predominant (85/95 [89.5%]) in XDR-TB strains, and as many as 40.0% (38/95) of the isolates were distributed into 6 clusters based on VNTR-16 genotyping and drug resistance mutation profiles. All isolates of each cluster harbored as many as six identical resistance mutations in the drug resistance genes rpoB, katG, inhA promoter, embB, rpsL, and gidB. Among the nine cases with continuous isolates from multidrug-resistant (MDR) to XDR-TB, 4 cases represented acquired drug resistance, 4 cases were caused by transmission, and 1 case was due to exogenous superinfection. The XDR-TB epidemic in China is mainly caused by a high degree of clonal transmission, but evolution from MDR to XDR and even superinfection with a new XDR strain can also occur.


Correlation between Trop2 and amphiregulin coexpression and overall survival in gastric cancer.
Gastric cancer (GC) is a multistep and multistage disease and the majority of GC cells could overexpressed one or more oncogenes. Trop2 and amphiregulin (AREG) are both overexpressed in various epithelial cell cancers and have the role in the increases tumor cells division and metastasis. However, little is known about the function and correlation of two oncogenes coexpressed in GC. The expression level of these two genes in 791 cases of GC tissues were tested, the correlations between two genes expression and clinical pathological characteristics and overall survival in GC patients through immunohistochemistry (IHC) were analyzed. This study also explored the mRNA expression level of two genes in 26 cases of freshly GC tissues by qRT-PCR. The results indicated that Trop2+/AREG+ coexpression was higher in GC tissues than in adjacent tissues. Trop2+/AREG+ protein coexpression were associated with Tumor Node Metastasis (TNM) stage (χ2 = 50.345, P < 0.001), tumor size (χ2 = 40.349, P < 0.001), lymph node metastases (χ2 = 26.481, P < 0.001), and distant metastases (χ2 = 8.387, P = 0.039). GC patients with Trop2+ and AREG+ protein coexpression had poor overall survival rates (HR = 3.682, 95% CI = 2.038-6.654, P < 0.001). The expression level of Trop2/AREG were positively correlated (r 0.254 and P < 0.001). The result of the mRNA expression was similar to that of the protein expression. Overall, Trop2 and AREG could be seen as prognostic cobiomarker in GC and combined detection of Trop2 and AREG could be viewed as helpful in predicting the prognosis of the GC patients.


Optical and structural characterisation of epitaxial nanoporous GaN grown by CVD.
In this paper we study the optical properties of nanoporous gallium nitride (GaN) epitaxial layers grown by chemical vapour deposition on non-porous GaN substrates, using photoluminescence, cathodoluminescence, and resonant Raman scattering, and correlate them with the structural characteristic of these films. We pay special attention to the analysis of the residual strain of the layers and the influence of the porosity in the light extraction. The nanoporous GaN epitaxial layers are under tensile strain, although the strain is progressively reduced as the deposition time and the thickness of the porous layer increases, becoming nearly strain free for a thickness of 1.7 μm. The analysis of the experimental data point to the existence of vacancy complexes as the main source of the tensile strain.


Pharmacophore Model Refinement for 11β-Hydroxysteroid Dehydrogenase Inhibitors: Search for Modulators of Intracellular Glucocorticoid Concentrations.
11β-Hydroxysteroid dehydrogenases (11β-HSD) control the intracellular concentrations of glucocorticoids: 11β-HSD1 converts the inactive cortisone to the active cortisol, and 11β-HSD2 is responsible for the opposite reaction. Inhibition of 11β-HSD1 is beneficial in the treatment of metabolic syndrome, whereas 11β-HSD2 inhibition leads to hypertension. Therefore, 11β-HSD1 inhibitors should be selective over 11β-HSD2. To support drug discovery and toxicological studies, we have previously reported pharmacophore models for 11β-HSD1 and 2 inhibition. These models represent the common chemical features of 11β-HSD inhibitors, which were used as virtual screening filter. Since new inhibitors are constantly discovered, the quality of the pharmacophore models has to be evaluated in order to maintain a good predictive power. In this study, we report a systematic evaluation and refinement of our pharmacophore model collection. We employed our models for virtual screening, especially focusing on the 11β-HSD2 inhibition. In total, 42 compounds were biologically evaluated and among these we discovered 17 11β-HSD inhibitors that decreased the residual enzyme activity to 50% or less at the concentration of 20 µM. The experimental 11β-HSD1 and 2 readouts from these compounds were used for further model refinement. Evaluation metrics were applied for a quantitative comparison of the old and newly generated models which resulted in a set of improved pharmacophore models offering reliable in silico tools for the identification of novel and selective 11β-HSD inhibitors.


How Can I Implement Accurate Delirium Screening and Prevention Practices?
As a clinical nurse specialist (CNS), I am tasked with improving patient outcomes through collaborative research, evidence-based practice, and process improvement efforts that affect the quality and safety of patient care. However, I have learned over time that it is not enough to simply incorporate the latest evidence into organizational policies and procedures; it has to be followed in practice. .


The katoite hydrogarnet Si-free Ca3Al2([OH]4)3: a periodic Hartree-Fock and B3-LYP study.
The structure of the Si-free katoite hydrogarnet (116 atoms in the unit cell) has been investigated at the periodic ab initio quantum mechanical level with the CRYSTAL program, by using a Gaussian type basis set and both the HF and the hybrid B3-LYP Hamiltonians. The structure has been fully optimized at various pressures in the 0-46 GPa range; the modifications of the structure, and in particular of the (OH)4 group, as a function of pressure are analyzed. At the B3-LYP level and P greater than 15 GPa, a O-H...O interaction of increasing strength appears, with important modifications in the local geometry of the tetrahedral site. The calculated omega01(O-H) fundamental vibrational frequency at zero pressure is in excellent agreement with experiment (3674 and 3663 cm(-1), respectively); the omega01(O-H) stretching frequency remains essentially constant in the 0-15 GPa interval, whereas it dramatically decreases at higher pressures with a corresponding anharmonicity increase, as a consequence of the formation of a strong hydrogen bond. The hydration energy of grossular and the formation energy of Si-free katoite have also been computed, and the B3-LYP results are in quite good agreement with experiment.


Dual-Task nTMS Mapping to Visualize the Cortico-Subcortical Language Network and Capture Postoperative Outcome-A Patient Series in Neurosurgery.
Perioperative assessment of language function in brain tumor patients commonly relies on administration of object naming during stimulation mapping. Ample research, however, points to the benefit of adding verb tasks to the testing paradigm in order to delineate and preserve postoperative language function more comprehensively. This research uses a case series approach to explore the feasibility and added value of a dual-task protocol that includes both a noun task (object naming) and a verb task (action naming) in perioperative delineation of language functions. Seven neurosurgical cases underwent perioperative language assessment with both object and action naming. This entailed preoperative baseline testing, preoperative stimulation mapping with navigated Transcranial Magnetic Stimulation (nTMS) with subsequent white matter visualization, intraoperative mapping with Direct Electrical Stimulation (DES) in 4 cases, and postoperative imaging and examination of language change. We observed a divergent pattern of language organization and decline between cases who showed lesions close to the delineated language network and hence underwent DES mapping, and those that did not. The latter displayed no new impairment postoperatively consistent with an unharmed network for the neural circuits of both object and action naming. For the cases who underwent DES, on the other hand, a higher sensitivity was found for action naming over object naming. Firstly, action naming preferentially predicted the overall language state compared to aphasia batteries. Secondly, it more accurately predicted intraoperative positive language areas as revealed by DES. Thirdly, double dissociations between postoperatively unimpaired object naming and impaired action naming and vice versa indicate segregated skills and neural representation for noun versus verb processing, especially in the ventral stream. Overlaying postoperative imaging with object and action naming networks revealed that dual-task nTMS mapping can explain the drop in performance in those cases where the network appeared in proximity to the resection cavity. Using a dual-task protocol for visualization of cortical and subcortical language areas through nTMS mapping proved to be able to capture network-to-deficit relations in our case series. Ultimately, adding action naming to clinical nTMS and DES mapping may help prevent postoperative deficits of this seemingly segregated skill.


The benefit of the diffusion kurtosis imaging in presurgical evaluation in patients with focal MR-negative epilepsy.
The effectivity of diffusion-weighted MRI methods in detecting the epileptogenic zone (EZ) was tested. Patients with refractory epilepsy (N=25) who subsequently underwent resective surgery were recruited. First, the extent of white matter (WM) asymmetry from mean kurtosis (MK) was calculated in order to detect the lobe with the strongest impairment. Second, a newly developed metric was used, reflecting a selection of brain areas with concurrently increased mean Diffusivity, reduced fractional Anisotropy, and reduced mean Kurtosis (iDrArK). A two-step EZ detection was performed as (1) lobe-specific detection, (2) iDrArK voxel-wise detection (with a possible lobe-specific restriction if the result of the first step was significant in a given subject). The method results were compared with the surgery resection zones. From the whole cohort (N=25), the numbers of patients with significant results were: 10 patients in lobe detection and 9 patients in EZ detection. From these subsets of patients with significant results, the impaired lobe was successfully detected with 100% accuracy; the EZ was successfully detected with 89% accuracy. The detection of the EZ using iDrArK was substantially more successful when compared with solo diffusional parameters (or their pairwise combinations). For a subgroup with significant results from step one (N=10), iDrArK without lobe restriction achieved 37.5% accuracy; lobe-restricted iDrArK achieved 100% accuracy. The study shows the plausibility of MK for detecting widespread WM changes and the benefit of combining different diffusional voxel-wise parameters.


Inclusion of supported gold nanoparticles into their semiconductor support.
Supported particles are easily accessible as standard materials used in heterogeneous catalysis and photocatalysis. This article addresses our exemplary studies on the integration of supported nanoparticles into their solid support, namely gold nanoparticles into zinc oxide sub-micrometer spheres, by energy controlled pulsed laser melting in a free liquid jet. This one-step, continuous flow-through processing route reverses the educt's structure, converting the ligand-free surface adsorbate into a spherical subsurface solid inclusion within its former support. The results show how a nanoparticulate surface adsorbate can be included in the form of crystalline nanoparticles into the resolidified support matrix, demonstrated by using plasmonic nanoparticles and semiconductor microparticles as reference materials.


A Highly Denaturant-durable Alginate Lyase from a Marine Bacterium: Purification and Properties.
Poly(α-L-guluronate)lyase, which depolymerizes polyguluronate of alginate, was purified from the culture medium of a marine bacterium isolated from the intestine contents of a red sea bream, Pagrus major. The enzyme was homogeneous as judged by polyacrylamide gel electrophoresis in the presence and absence of SDS and the molecular weight of 42,000 and 40,000 on SDS gel electrophoresis and on a Sephacryl S200HR column chromatography, respectively. The activity of the enzyme was higher at around pH 8.5 and stable from pH 6-10. The active form of the enzyme, which has been thought to be once lost upon incubation of the enzyme at higher temperatures up to 80°C could be restored on cooling the enzyme. The residual activity was 45% even at 100°C. By treatment with other denaturants, the activity was maintained in 3% SDS and was 70% in 6M GHCI and 60% in 4M urea on incubation at 25°C for 30 min. In addition, several chemical· reagents were tested for the relationship between the functional amino acid residue and the active form of the enzyme.


Total synthesis of (-)-norzoanthamine.
No bones about it: (-)-Norzoanthamine, a promising candidate for an anti-osteoporotic drug, was the target of a total synthesis (see scheme). The final bisaminal formation with AcOH/H(2)O gave the DEFG ring, while the cyclization precursor was prepared by installing the remaining bisaminal unit after oxidative cleavage of the cyclopentanol moiety.


The relationship between mean square differences and standard error of measurement: comment on Barchard (2012).
In the discussion of mean square difference (MSD) and standard error of measurement (SEM), Barchard (2012) concluded that the MSD between 2 sets of test scores is greater than 2(SEM)² and SEM underestimates the score difference between 2 tests when the 2 tests are not parallel. This conclusion has limitations for 2 reasons. First, strictly speaking, MSD should not be compared to SEM because they measure different things, have different assumptions, and capture different sources of errors. Second, the related proof and conclusions in Barchard hold only under the assumptions of equal reliabilities, homogeneous variances, and independent measurement errors. To address the limitations, we propose that MSD should be compared to the standard error of measurement of difference scores (SEMx-y) so that the comparison can be extended to the conditions when 2 tests have unequal reliabilities and score variances.


Effects of different running programs on VO2 max, percent fat, and plasma lipids.
This study attempted to determine the effects of interval and continuous running on factors associated with cardiovascular health. Fifty-nine untrained men and women, ages 18-32 years, were randomly assigned to one of four groups: (1) 4 mile: running continuously at 75% of maximal heart rate (approximately 500 Cal/session) (2) 2 mile: running continuously at 75% of maximal heart rate (approximately 250 Cal/session) (3) interval: running one min at 90% maximal heart rate followed by three min of walking for eight sets (approximately 500 Cal/session) (4) control: no exercise program. The training was performed three times per week for 12 weeks. Treadmill VO2 max and percent body fat by hydrostatic weighing were assessed pre- and post training. Pre and post analyses were performed on plasma for triglycerides (TG), cholesterol (Chol), and high density lipoprotein cholesterol (HDL-C). Analysis of covariance indicated that only the interval group improved more than the control in VO2 max. Percent fat decreased in all exercise groups, but no program was superior. Changes in TG, Chol, or HDL-C were not different among groups. Although men and women differed on the pretests in VO2 max, percent fat, and HDL-C, their response to the training was similar. These results indicate that interval training may benefit aerobic capacity more than continuous running in young adults who have moderately high initial fitness levels. The data also indicate that cardiovascular fitness parameters are not easily altered by short term exercise in young active men and women.


Statistical Considerations for Embedded Pragmatic Clinical Trials in People Living with Dementia.
There is overwhelming need for nonpharmacological interventions to improve the health and well-being of people living with dementia (PLWD). The National Institute on Aging Imbedded Pragmatic Alzheimer's Disease (AD) and AD-Related Dementias Clinical Trials (IMPACT) Collaboratory supports clinical trials of such interventions embedded in healthcare systems. The embedded pragmatic clinical trial (ePCT) is ideally suited to testing the effectiveness of complex interventions in vulnerable populations at the point of care. These trials, however, are complex to conduct and interpret, and face challenges in efficiency (i.e., statistical power) and reproducibility. In addition, trials conducted among PLWD present specific statistical challenges, including difficulty in outcomes ascertainment from PLWD, necessitating reliance on reports by caregivers, and heterogeneity in measurements across different settings or populations. These and other challenges undercut the reliability of measurement, the feasibility of capturing outcomes using pragmatic designs, and the ability to validly estimate interventions' effectiveness in real-world settings. To address these challenges, the IMPACT Collaboratory has convened a Design and Statistics Core, the goals of which are: to support the design and conduct of ePCTs directed toward PLWD and their caregivers; to develop guidance for conducting embedded trials in this population; and to educate quantitative and clinical scientists in the design, conduct, and analysis of these trials. In this article, we discuss some of the contemporary methodological challenges in this area and develop a set of research priorities the Design and Statistics Core will undertake to meet these goals. J Am Geriatr Soc 68:S68-S73, 2020.


Emerging bronchoscopic treatments for chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by pathophysiological factors including airflow limitation, hyperinflation and reduced gas exchange. Treatment consists of lifestyle changes, lung rehabilitation and pharmacological therapies such as long acting beta-2-agonists (LABA) and long acting muscarinic antagonists (LAMA). More recently bronchoscopic treatments are emerging for COPD. Among them endobronchial valves (EBV) and endobronchial coils (EBC), next to endobronchial stents, sclerosing agents, targeted lung denervation and liquid nitrogen metered cryospray. In this review we aim to summarize the new emerging bronchoscopic treatments and their effect sizes compared with lung rehabilitation and pharmacological therapies.


Adverse drug interactions in dental practice: interactions associated with local anesthetics, sedatives and anxiolytics. Part IV of a series.
This article is the fourth in a five-part series based on a 1998 International Association for Dental Research symposium entitled "Adverse Drug Interactions in Dentistry: Separating the Myths From the Facts." The symposium evaluated the significance of various drug interactions associated with dental therapeutics. Local anesthesia and preoperative oral sedative/anxiolytic therapy often are indicated for routine oral surgery and restorative dentistry. The author conducted a literature review of the drug interactions associated with the use of local anesthetics and sedatives. The quality of the information used to document these interactions and the severity of the possible adverse outcome were assessed using a significance rating scale for dental drug interactions. Many of the frequently described drug interactions were found to be poorly documented in the dental and medical literature. Others were determined not to be relevant to current dental practice. The use of local anesthetics, sedatives or anxiolytic agents in combination with other central nervous system depressant agents or in combination with drugs that inhibit their metabolism was associated with a few serious adverse drug interactions or complications. The adverse drug interactions associated with the use of local anesthetics and oral sedative/anxiolytic agents in general practice vary in significance. An understanding of possible adverse drug interactions in dentistry may help practitioners avoid and prevent these complications.


Hypoxia and inflammation indicate significant differences in the severity of obstructive sleep apnea within similar apnea-hypopnea index groups.
We determined whether hypoxia parameters are associated with C-reactive protein (CRP), mean platelet volume (MPV), white matter hyperintensity (WMH), and the severity of obstructive sleep apnea (OSA), and also evaluated whether hypoxia parameters, CRP, MPV, and WMH differ in patients with similar apnea-hypopnea index (AHI) scores. A total of 297 patients, who were evaluated using polysomnography, were assessed retrospectively. The measured hypoxia parameters included total sleep time with oxygen saturation <90% (ST90), percentage of cumulative time with oxygen saturation <90% (CT90), and lowest oxygen saturation (min SaO2). The patients were divided into subgroups according to their CT90 values, and patients with different AHI severities were divided into subgroups according to their ST90 and min SaO2 levels. Hypoxia parameters are associated with CRP, MPV, WMH, and the severity of OSA (P < 0.05). The hypoxia parameters differed in all subgroup analyses of similar AHI groups (P < 0.001), and CRP differed only in severe OSA (P < 0.008, P < 0.001). In subgroup analyses of similar AHI groups, MPV and WMH were not significantly different (P > 0.05). Above the hypoxia threshold (CT90 ≥ 10%) of CRP, MPV increased significantly and the presence of WMH increased twofold. These data suggest that increased hypoxia severity may mediate increased inflammation and activation of platelets and contribute to the pathogenesis of WMH in patients with OSA. In addition, patients with severe OSA may show significant variability in inflammation and vascular risk. Further prospective data are needed.


Loss of function mutations in RPL27 and RPS27 identified by whole-exome sequencing in Diamond-Blackfan anaemia.
Diamond-Blackfan anaemia is a congenital bone marrow failure syndrome that is characterized by red blood cell aplasia. The disease has been associated with mutations or large deletions in 11 ribosomal protein genes including RPS7, RPS10, RPS17, RPS19, RPS24, RPS26, RPS29, RPL5, RPL11, RPL26 and RPL35A as well as GATA1 in more than 50% of patients. However, the molecular aetiology of many Diamond-Blackfan anaemia cases remains to be uncovered. To identify new mutations responsible for Diamond-Blackfan anaemia, we performed whole-exome sequencing analysis of 48 patients with no documented mutations/deletions involving known Diamond-Blackfan anaemia genes except for RPS7, RPL26, RPS29 and GATA1. Here, we identified a de novo splicing error mutation in RPL27 and frameshift deletion in RPS27 in sporadic patients with Diamond-Blackfan anaemia. In vitro knockdown of gene expression disturbed pre-ribosomal RNA processing. Zebrafish models of rpl27 and rps27 mutations showed impairments of erythrocyte production and tail and/or brain development. Additional novel mutations were found in eight patients, including RPL3L, RPL6, RPL7L1T, RPL8, RPL13, RPL14, RPL18A and RPL31. In conclusion, we identified novel germline mutations of two ribosomal protein genes responsible for Diamond-Blackfan anaemia, further confirming the concept that mutations in ribosomal protein genes lead to Diamond-Blackfan anaemia.


Use of lambda gt11 and monoclonal antibodies to map the genes for the six major glycoproteins of equine herpesvirus 1.
To localize the genes for the major glycoproteins of equine herpesvirus 1 (EHV-1), a library of the EHV-1 genome was constructed in the lambda gt11 expression vector. Recombinant bacteriophage expressing EHV-1 glycoprotein epitopes as fusion products with beta-galactosidase were detected by immunoscreening with monoclonal antibodies specific for each of six EHV-1 glycoproteins. Seventy-four recombinant lambda gt11 clones reactive with EHV-1 monoclonal antibodies were detected among 4 X 10(5) phage screened. Phage expressing determinants on each of the six EHV-1 glycoproteins were represented in the library. Herpesviral DNA sequences contained in lambda gt11 recombinants expressing epitopes of EHV-1 glycoproteins were used as hybridization probes for mapping insert sequences on the viral genome. Genes for five EHV-1 glycoproteins (gp2, gp10, gp13, gp14, and gp21/22a) mapped to the genome L component; only one EHV-1 glycoprotein (gp17/18) was expressed from the unique S region of the genome where genes of several major glycoproteins of other herpesviruses have been located. Two glycoproteins of EHV-1, gp13 and gp14, mapped to positions colinear with genes of major glycoproteins identified in several other alphaherpesviruses (gC- and gB-like glycoproteins, respectively). The genomic locations of other EHV-1 glycoproteins indicated the existence of major glycoproteins of EHV-1 (gp2, gp10, and gp21/22a) for which no genetic homologs have yet been detected in other herpesviruses. The results confirm the general utility of the lambda gt11 expression system for localizing herpesvirus genes and suggest that the genomic positioning of several high-abundance glycoproteins of EHV-1 may be different from that of the prototype alphaherpesvirus, herpes simplex virus.


Correlation between clinical tests and electroneuromyography for the diagnosis of leprosy neuropathy.
In leprosy, sensory function of nerves is evaluated with monofilaments test and the motor function with voluntary muscle test, however electroneuromyography is considered as the gold-standard tool. This study aimed: i) to evaluate the correlation between clinical tests and electroneuromyography for the diagnosis of leprosy neuropathy; and ii) to identify the prevalence of leprosy neuropathy and the most compromised peripheral nerves in leprosy. We analysed the data from a nested case-control study that identified 166 patients diagnosed with leprosy neuropathy confirmed by electromyography. This study was designed for an analysis of correlation between the diagnostic tests. The most prevalent type of the neural damage was the sensory and motor multiple mononeuropathy, observed in 62 (37.3%) cases. The highest prevalence was the ulnar nerve in 67 (40.3%) cases. Agreement specified by nerves was moderate, ranging from k = 0.58 in the deep peroneal nerve to k = 0.41 in the posterior tibial nerve). Overall agreement between the clinical tests and electroneuromyography was very poor. Monofilaments test with k = 0.02 (95% CI 0.00-0.12) and voluntary muscle test with 0.16 (95% CI 0.04 to 0.28, P = 0.01). There is a low to moderate correlation between clinical tests (monofilaments and voluntary muscle tests) and the electroneuromyography examination. The most prevalent type of neural impairment was the sensory and motor multiple mononeuropathy, and the most affected nerve was the ulnar.


The quality and cost of medical care in Sweden.
Swedish examples are used in favor of recent WHO recommendations of quality assurance. Even prior to present efforts at savings, the autopsy frequency in Swedish hospitals dropped 2% per year. Only 31% of Swedish out-patients see the same doctor on subsequent visits, and since few have a personal physician, emergency ward visits increase about 4% per year. Laboratory errors and uncertain diagnoses seem to be of the order of 20%, at least in some conditions.


Effect of increasing salinity to adapted and non-adapted Anammox biofilms.
The Anammox process is an efficient low energy alternative for the elimination of nitrogen from wastewater. The process is already in use for side stream applications. However, some industrial wastewaters, e.g. from textile industry are highly saline. This may be a limit for the application of the Anammox process. The aim of this study was to evaluate the effects of different NaCl concentrations on the efficiency of adapted and non-adapted Anammox biofilms. The tested NaCl concentrations ranged from 0 to 50 g NaCl*L-1. Concentrations below 30 g NaCl*L-1 did not significantly result in different nitrogen removal rates between adapted and non-adapted bacteria. However, adapted bacteria were significantly more resilient to salt at higher concentrations (40 and 50 g NaCl*L-1). The IC50 for adapted and non-adapted Anammox bacteria were 19.99 and 20.30 g NaCl*L-1, respectively. Whereas adapted biomass depletes the nitrogen in ratios of NO2- / NH4+ around 1.20 indicating a mainly Anammox-driven consumption of the nitrogen, the ratio increases to 2.21 at 40 g NaCl*L-1 for non-adapted biomass. This indicates an increase of other processes like denitrification. At lower NaCL concentrations up to 10 g NaCl*L-1, a stimulating effect of NaCl to the Anammox process has been observed.


Continuous theta burst transcranial magnetic stimulation affects brain functional connectivity.
Prefrontal cortex (PFC) plays an important role in the emotional processing as well as in the functional brain network. Hyperactivity in the right dorsolateral prefrontal cortex (DLPFC) would be found in anxious participants. However, it is still unclear what the role of PFC played in a resting functional network. Continuous theta burst transcranial magnetic stimulation (cTBS) is an effective tool to create virtual lesions on brain regions. In this paper, we applied cTBS over right prefrontal area, and investigated the effects of cTBS on the brain activity for functional connectivity by the method of graph theory. We recorded 64-channels EEG on thirteen healthy participants in the resting condition and emotional tasks before and after 40 s of cTBS. This work focused on the effect of cTBS on cortical activities in the resting condition by calculating the coherence between EEG channels and building functional networks before and after cTBS in the delta, theta, alpha and beta bands. Results revealed that 1) The functional connectivity after cTBS was significantly increased compared with that before cTBS in delta, theta, alpha and beta bands in the resting condition; 2) The efficiency-cost reached the maximum before and after cTBS both with the cost about 0.3 in the bands above, which meant that the information transmission of functional brain network with this cost was highly efficient; 3) the clustering coefficient and path length after cTBS was significantly increased in delta, theta and beta bands. In conclusion, cTBS over PFC indeed enhanced the functional connectivity in the resting condition. In addition, the information transmission in the resting brain network was highly efficient with the cost about 0.3.


Effects of fragmentation on the seed predation and dispersal by rodents differ among species with different seed size.
Fragmentation influences the population dynamics and community composition of vertebrate animals. Fragmentation effects on rodent species in forests may, in turn, affect seed predation and dispersal of many plant species. Previous studies have usually addressed this question by monitoring a single species, and their results are contradictory. Very few studies have discussed the fragmentation effect on rodent-seed interaction among tree species with different seed sizes, which can significantly influence rodent foraging preference and seed fate. Given that fruiting periods for many coexisting plant species overlap, the changing foraging preference of rodents may substantially alter plant communities. In this study, we monitored the dispersal and predation by rodents of 9600 seeds, belonging to 4 Fagaceae species with great variation in seed size, in both the edge and interior areas of 12 tropical forest fragments ranging in area from 6.3 to 13872.9 ha in Southwest China. The results showed that forest fragmentation altered the seed fates of all the species, but the intensity and even the direction of fragmentation effect differed between species with large versus small seeds. For the seeds harvested, fragment size showed negative effects in forest interiors but positive effects at edges for the 2 large-seeded species, but showed little effect for the 2 small-seeded species. For the seeds removed, negative effects of fragment size only existed among the small-seeded species. The different fragmentation effect on seed dispersal and predation among plant species may, in turn, translate into the composition differences of the regeneration of the whole fragmented forest.


A new nonpolar N-hydroxy imidazoline lead compound with improved activity in a murine model of late-stage Trypanosoma brucei brucei infection is not cross-resistant with diamidines.
Treatment of late-stage sleeping sickness requires drugs that can cross the blood-brain barrier (BBB) to reach the parasites located in the brain. We report here the synthesis and evaluation of four new N-hydroxy and 12 new N-alkoxy derivatives of bisimidazoline leads as potential agents for the treatment of late-stage sleeping sickness. These compounds, which have reduced basicity compared to the parent leads (i.e., are less ionized at physiological pH), were evaluated in vitro against Trypanosoma brucei rhodesiense and in vivo in murine models of first- and second-stage sleeping sickness. Resistance profile, physicochemical parameters, in vitro BBB permeability, and microsomal stability also were determined. The N-hydroxy imidazoline analogues were the most effective in vivo, with 4-((1-hydroxy-4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((1-hydroxy-4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)benzamide (14d) showing 100% cures in the first-stage disease, while 15d, 16d, and 17d appeared to slightly improve survival. In addition, 14d showed weak activity in the chronic model of central nervous system infection in mice. No evidence of reduction of this compound with hepatic microsomes and mitochondria was found in vitro, suggesting that N-hydroxy imidazolines are metabolically stable and have intrinsic activity against T. brucei. In contrast to its unsubstituted parent compound, the uptake of 14d in T. brucei was independent of known drug transporters (i.e., T. brucei AT1/P2 and HAPT), indicating a lower predisposition to cross-resistance with other diamidines and arsenical drugs. Hence, the N-hydroxy bisimidazolines (14d in particular) represent a new class of promising antitrypanosomal agents.


[Case of pancreatic endocrine tumor associated with Cushing's syndrome].
A 78-year-old woman was admitted complaining of edema of the bilateral lower extremities and face. Computed tomography (CT) and ultrasonography (US) of her abdomen revealed a pancreatic tumor and multiple liver metastases. After admission, hypokalemia and muscle weakness and edema of the bilateral lower extremities rapidly worsened. The diagnosis of Cushing's syndrome was established based on clinical and biochemical data and endocrine studies. We thought that the primary tumor was a pancreatic endocrine tumor based on the liver tumor biopsy findings, and that the pancreatic tumor and liver metastatic tumors were ectopic ACTH-producing tumors. A case of pancreatic endocrine tumor associated with Cushing's syndrome is relatively rare. We summarize previous reports.


Identification and production of a bacteriocin from Enterococcus mundtii QU 2 isolated from soybean.
Identification of the bacteriocin produced by Enterococcus mundtii QU 2 newly isolated from soybean and fermentative production of the bacteriocin. The bacteriocin produced by Ent. mundtii QU 2 inhibited the growth of various indicator strains, including Enterococcus, Lactobacillus, Leuconostoc, Pediococcus and Listeria. The bacteriocin activity was stable at wide pH range and against heat treatment, but completely abolished by proteolytic enzymes. The bacteriocin was purified from the culture supernatant by the three-step chromatographic procedure. Mass spectrometry, amino acid sequencing and DNA sequencing revealed that the bacteriocin was similar to class IIa bacteriocins produced by other Ent. mundtii strains. The bacteriocin production decreased in the absence of glucose, nitrogen sources, or Tween 80 in MRS medium. Additionally, it was strongly suppressed by addition of Ca(2+) (CaCO(3) or CaCl(2)). In pH-controlled fermentations, the highest bacteriocin production was achieved at pH 6.0, whereas the highest cell growth was obtained at pH 7.0. Ent. mundtii QU 2 produced a class IIa bacteriocin. Some growth factors (e.g. Ca(2+) and pH) influenced the bacteriocin production. A new soybean isolate, Ent. mundtii QU 2 was found to be a class IIa bacteriocin producer. Factors influencing the bacteriocin production described herein are valuable for applications of the bacteriocins from Ent. mundtii strains.


Therapeutic hypothermia, still "too cool to be true?".
Therapeutic hypothermia, an intervention reducing core body temperature below 35 degrees Celsius, has gained popularity in the management of acute brain injury after a series of small clinical trials in patients following cardiac arrest, stroke and traumatic brain injury. This article reviews the evidence relating to therapeutic hypothermia as an intervention in acute injury.


A tradeoff between the losses caused by computer viruses and the risk of the manpower shortage.
This article addresses the tradeoff between the losses caused by a new virus and the size of the team for developing an antivirus against the virus. First, an individual-level virus spreading model is proposed to capture the spreading process of the virus before the appearance of its natural enemy. On this basis, the tradeoff problem is modeled as a discrete optimization problem. Next, the influences of different factors, including the infection force, the infection function, the available manpower, the alarm threshold, the antivirus development effort and the network topology, on the optimal team size are examined through computer simulations. This work takes the first step toward the tradeoff problem, and the findings are instructive to the decision makers of network security companies.


Meso-American nephropathy: what we have learned about the potential genetic influence on chronic kidney disease development.
Chronic kidney disease of unknown aetiology (CKDu) refers to the epidemic level of incidence of CKD in several low- and middle-income countries, usually near the equator, for which the aetiology has not been identified. CKDu represents a form of CKD hotspot, defined as a country, region, community or ethnicity with a higher than average incidence of CKD. In terms of the number of persons affected, the so-called hypertensive nephropathy of African Americans probably represents the largest CKD hotspot, which is largely driven by variants of the APOL1 gene, questioning the very existence of hypertensive nephropathy and illustrating how kidney disease driven by genetic predisposition may underlie some forms of hypertension. For CKDu, hard physical work leading to dehydration (the first global warming-related disease?) and local toxins are leading aetiological candidates. Meso-American nephropathy is probably the best-characterized CKDu. In this issue of CKJ, a systematic review and meta-analysis by Gonzalez et al. identified positive associations between Meso-American nephropathy and male gender, family history of CKD, high water intake and lowland altitude. We now discuss the potential relationship of family history to genetic predisposition and how a better understanding of CKDu may help advance the aetiological characterization of the nearly 50% of end-stage renal disease patients worldwide that have no known cause for CKD or have been assigned non-specific diagnoses.


Human leukocyte antigen in genodermatosis.
Tissue typing performed on the lymphocytes of 41 patients, including: 23 patients with ichthyosis (15 of autosomal dominant and 8 of the x-linked variety; 8 patients with tuberous sclerosis (epiloia); and 10 patients with acrodermatitis enteropathica (AEP). In addition, tissue typing was performed for a control group of 80 healthy unrelated subjects of the same ethnic origin as the patients. A significant increase of A2 antigen or its crossreacting antigen A28 was detected among the three diseases studied. A significant increase of HLA-A2 antigen was found in autosomal dominant ichthyosis, while the x-linked variety showed significant association with HLA-Cw2. A significant association with HLA-A28 antigen was noticed in both epiloia and AEP. The suggested mechanisms of such association may be referred to as incidental genetic linkage with mutants causing disease or deficiency.


Elemental composition of Marrubium astracanicum Jacq. growing in tungsten-contaminated sites.
This study evaluates the elemental (W, Mo, Zn, Fe, Cu, Cd, Mn, Pb, Cr, Co, B, and Bi) composition of Marrubium astracanicum Jacq. (Lamiaceae), around the abandoned tungsten mine on Uludağ Mountain, Turkey, to determine if it is an appropriate candidate for phytomonitoring and/or phytoremediation purposes. Three sample sites were selected around the mine for soil and plant sampling. Two sites approximately 500 m from the mine were assumed to be unpolluted sites. The other site was selected from a waste removal pool (WRP) and was assumed to be a polluted site. The soil and different organs (roots, leaves, and flowers) of plant samples were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS) to determine the elemental content. The classic open wet digestion procedure was applied to the samples with 5 mL HNO3 and 3 mL H2O2 in a borosilicate glass vessel for the roots, leaves, and the flowers of the plants. Kjeldahl digestion was used for the soil samples. The W, Zn, Fe, Cu, Cd, Mn, Pb, B, and Bi contents were found to be higher in the soil samples from the waste removal pools compared with the samples from the unpolluted sites. We also found that the elemental composition of M. astracanicum has generally been increased by the activity of the tungsten mine, and there were significant correlations between the elemental contents of the soil samples and plant parts, except for Mo and Cr. The high level of many elements in the soil samples indicates the presence of contamination related to tungsten-mining activity on Uludağ Mountain. Assessing the elemental contents of M. astracanicum, we can suggest this species as a candidate for phytoremediation purposes of W-contaminated sites due to its high W-accumulation capacity.


Potential malignant transformation in the gastric mucosa of immunodeficient mice with persistent Mycoplasma penetrans infection.
Mycoplasma infection has been reported in immunocompromised cancer patients; nevertheless, it is not clear if persistent Mycoplasma infection could facilitate the proliferation of cancer cells in immunocompromised organisms. The aim of this study was to examine the relationship between persistent Mycoplasma infection and malignant transformation in an immunodeficient host model. Immunodeficient mouse model was established using cyclophosphamide and mice gastric mucosal cells were infected with Mycoplasma penetrans (Mpe). After 18 weeks, mice were sacrificed and gastric mucosal Mpe infected cells were identified by fluorescence in situ hybridization (FISH). Moreover, pathological and ultrastructural changes in mice gastric mucosa were evaluated and the expression of multiple proto-oncogenes was examined by Western blot. Our data show that Mpe infection was detected in the blood of immunodeficient mice and Mpe persistent infection in mice gastric mucosa was confirmed by FISH. There were pathological and ultrastructural malignant transformation occurred in the gastric mucosa of infected mice compared to control mice. Mpe infected mice showed lower expression of p53 and p21 and higher H-ras expression compared to the control group. Moreover, expression of NF-κB p65 subunit increased in Mpe infected mice, similar to the TNF-α expression. Bax expression in gastric mucosa of Mpe infected mice was lower while Bcl-2 expression was higher than in the uninfected control group. Collectively these data demonstrate that persistent Mpe infection is associated with aberrant expression of multiple proto-oncogenes in gastric mucosa of immunodeficient mice which potentially facilitate the malignant transformation.


[Bronchial asthma: clinico-pathological study of fatalities in intensive care units].
Due to the great amount of asthmatic patients presenting complications which could endanger their lives, a revision of the possible threatening factors is carried out. The factors concurring with the base pathologic mechanism are analyzed and it is demonstrated, that some of these factors intervene independently from bronchial asthma. The study is carried out on the basis of age, sex, hospital stay duration, clinical picture, blood gases analysis, complications and pathology findings: 1) Most of the deceased patients presented various pathologies besides bronchial asthma which contributed to the decease. 2) The physician should be alert in order to establish good therapeutic procedure in these patients which could carry other important complications; these complications are responsible for the fatal outcome in a great number of patients. A complication should always be searched for, e.g. pneumothorax. 3) The vast majority of patients who passed away in status were relatively young. 4) A female predominance was found. 5) All patients before entering our Center, presented asthma crisis at least three days prior to admission. 6) The predominant hospital stay duration was 24 hours. 7) The most common pathologic findings were: pulmonary fibroemphysema, acute bronchopneumonia, bronchial mucoid plugging, atelectasia and cerebral edema. 8) Cerebral edema and compression of the amygdale were common brain pathologic findings. 9) Bronchopneumonia was a common necropsy finding. 10) Based on these findings, ICU treatment is extremely important. 11) The critical status of the patient in the moment of admission, is due to the delay in bringing him to the hospital for proper medical surveyance. This justifies the interest of the Public Health Department in ample distribution of proper information to the asthmatic patients.