Decomposition of paper wastes in presence of ceramics and cement raw material.
Paper recycling is an environmental important activity that is carried out in all the countries, but during the recycling process a paper waste is produced. Generally these wastes are placed in landfill sites but it is possible to profit it as secondary fuel and raw material in manufacture furnaces. In this work the combustion of the waste papers with cement and ceramic raw material has been studied with the objective to analyse the interaction of these substances with the emitted pollutants like PAHs and PCDD/Fs. The results of the study show that the presence of inorganic material produces an increment in the lighter PAH emission but chlorinated compounds are not affected. The PCDD/F emission level found in the combustion of this waste is quite low compared with other wastes subjected to similar conditions.


Kombucha ameliorates experimental autoimmune encephalomyelitis through activation of Treg and Th2 cells.
Multiple sclerosis (MS) is the most common inflammatory disorder of the central nervous system (CNS). Kombucha is produced by the fermentation of sugared tea with a symbiotic culture of bacteria and yeasts. This research was designed to reveal the therapeutic impact and the molecular and cellular processes determining the effect of kombucha on MS alleviation in an experimental autoimmune encephalomyelitis (EAE). The EAE was induced using myelin oligodendrocyte glycoprotein (MOG35-55) peptide emulsified in CFA and injected subcutaneously over two flank areas in C57BL/6 mice. In addition, pertussis toxin was injected intraperitoneally and repeated 48 h later. Treatment groups were received three different doses of kombucha (K1: low dose, K2: medium dose and K3: high dose) to obtain a maximum protection. Clinical scores and other criteria were followed daily for the 25 days. At the end of the course, T-helper-related cytokines (IFN-γ, IL-17, IL-4, and TGF-β) were measured through ELISA. Moreover, nitric oxide (NO) concentration in spinal cord tissue was detected. The severity of disease on the peak of disease in K1, K2, and K3 groups were 3.4 ± 0.18 and 2.6 ± 0.18 and 2 ± 0.14 respectively, compared to the CTRL group with 4.5 ± 0.19 (p < 0.001). Kombucha increased production of interleukin IL-4 (K1 = 95 ± 5, K2 = 110 ± 10, K3 = 115 ± 5 and CTRL = 65 ± 5; p < 0.05) and TGF-β (K1 = 1750 ± 80, K2 = 2050 ± 65, K3 = 2200 ± 75 and CTRL = 850 ± 85; p < 0.001) but concurrently resulted in a remarkable reduction in the production of IFN-γ (K1 = 950 ± 70, K2 = 890 ± 65, K3 = 850 ± 85 and CTRL = 3850 ± 115; p < 0.001) and IL-17 (K1 = 1250 ± 75, K2 = 1050 ± 90, K3 = 970 ± 80 and CTRL = 6450 ± 125; p < 0.001). Moreover, NO concentration in spinal cord tissue in the treatment groups was significantly less than the control group (K1: 35.42 ± 2.1, K2 = 31.21 ± 2.2, K3 = 28.24 ± 2.6 and CTRL = 45.25 ± 2.7; p < 0.05). These results supported that kombucha could reduce the severity of disease in an EAE model through motivating polarization of CD4+ T cells by induction of IL-4 and TGF-β as well as inhibition of IFN-γ and IL-17.


Endovascular Treatment of Infra-inguinal Arterial Occlusive Disease in Patients with Diabetes.
To present the early and mid-term results of PTA for femoropopliteal lesions in diabetic patients, performed by the cardiovascular surgeons. Experimental study. Department of Cardiovascular Surgery, Ankara City Hospital, Turkey, from August 2015 to April 2018. Seventy-nine patients with diabetes mellitus (DM) and lower limb arterial occlusive disease underwent endo-interventions causing Rutherford Class 2-5 pedal ischemia. Study end points included ankle brachial index (ABI) and primary patency (PP) evaluated through Kaplan-Meier analyses. The technical success rate was 92.4% with a mean follow-up period of 13.3 ± 9.2 months. Bailout stenting was required in 27 (34.2%) of the lesions and only 7 (8.9%) patients required percutaneous reintervention at the end of the follow-up period. Kaplan-Meier analysis of the bailout stenting group revealed higher primary patency and lower reintervention rates at 24 months when compared with the PTA group (70.8%, 57.7% and 80.5% 65.9%, respectively). Endovascular procedures can be performed by cardiovascular surgeons in the early and mid-term with high success and low complication rates in patients with diabetes mellitus. Key Words: Percutaneous transluminal angioplasty, Endovascular arterial intervention, Diabetes, Femoro-popliteal occlusion, Revascularisation, Lower limb arterial occlusion.


Bilateral occlusion of the cervical internal carotid arteries: a case with an unusual co-lateral circulation.
The case of a man, aged 67,who had bilateral occlusion of the cervical internal carotid arteries with an unusual collateral circulation between the occipital artery and the anterior cerebral artery, is described.


An environmentally relevant mixture of organochlorines, their metabolites and effects on preimplantation development of porcine embryos.
Environmental exposure of human populations to organochlorines is still widespread despite several international regulations banning or restricting their use. This study tested the hypothesis that an environmentally relevant complex mixture of organochlorines comprising polychlorinated biphenyls (PCBs), technical chlordane, dichlorodiphenyldichloroethylene and 12 other components is toxic for porcine embryos (at relative concentrations of 1-10000-fold the environmental organochlorine levels of contamination or 4.2 microg/l total PCBs). We also tested the embryotoxicity of a metabolised organochlorine mixture (relative concentrations of 0.9, 1.8, 2.7, 3.6 and 4.5 microg/l hydroxy-PCBs (OH-PCBs)) obtained by extracting plasma samples from sows treated with the native mixture. Embryos produced in vitro were exposed to either the organochlorine mixture or the metabolised extract for 9 days. The organochlorine mixture reduced embryonic development at the 10000x concentration (relative concentration of 42 mg/l PCBs; p=0.05). The organochlorine mixture also reduced the mean number of blastomeres per expanded blastocyst in a dose-dependent manner (p=0.038) but did not induce blastomere apoptosis (p>0.05). In contrast, the metabolised extract did not affect development or blastomere number at the concentrations tested, although the highest level of this mixture (4.5 microg/l OH-PCBs) was still very low (i.e. similar to the 1x concentration of the organochlorine mixture, which also did not alter embryo parameters). These data lead to the conclusion that while high concentrations of the native organochlorine mixture are toxic for porcine embryos, concentrations of either the native or the metabolised mixture that bear some relevance to exposure of human populations in the Arctic were without observable effect.


Possible involvement of endothelin peptides and L-arginine-nitric oxide pathway on the effect of endotoxin in the rabbit isolated perfused kidney.
Escherichia coli endotoxin (LPS) when infused through the renal artery of the rabbit isolated perfused kidney prepared as constant pressure mode, caused a decrease in flow rate and kidney weight indicating its primary vasoconstrictor effect. This effect was predominant in kidneys from rabbits pretreated with LPS. Endothelin-1 at a concentration of 10(-10) M and big endothelin-1 at a concentration of 10(-8) M produced equal vasoconstrictor effects in kidney. Addition of endotheHn converting enzyme inhibitor, phosphoramidon, to the perfusion medium at a concentration of 10(-6) M caused a reduction in the effects of both LPS and big ET-1 without altering the vasoconstrictor effect of ETol. However, addition of methylene blue (10(-5) M), a soluble guanylate cyclase inhibitor and N(G)-nitro-L-arginine-methyl ester (10(-6) M) to the perfusion medium caused a potentiation in the vasoconstrictor effect of LPS. Indomethacin at a concentration of 10(-6) M did not alter the effect of LPS. These results were taken as evidence for the participation of endothelin peptides and the L-arginine-nitric oxide pathway in the effect ofLPS in rabbit isolated perfused kidney.


Participant withdrawal: challenges and practical solutions for recruitment and retention in clinical trials.
A major challenge in the conduct of clinical trials is recruiting and retaining adequate numbers of study participants. Pressure for steady recruitment and retention is great. A wide range of strategies are used to retain participants; however, some approaches raise ethical questions. This article examines issues of participant retention, literature addressing the volunteer nature of informed consent, the moral distress surrounding participant withdrawal, and potential ethical implications. Strategies are proposed to resolve issues and reduce participant and investigator distress. Case studies of two patients with complex chronic illnesses illustrate practical solutions and lessons learned.


Genetic Testing in the Multidisciplinary Management of Melanoma.
Melanoma is increasing in incidence and represents an aggressive type of cancer. Efforts have focused on identifying genetic factors in melanoma carcinogenesis to guide prevention, screening, early detection, and targeted therapy. This article reviews the hereditary risk factors associated with melanoma and the known molecular pathways and genetic mutations associated with this disease. This article also explores the controversies associated with genetic testing and the latest advances in identifying genetic targets in melanoma, which offer promise for future application in the multidisciplinary management of melanoma.


In vitro wearing away of orthodontic brackets and wires in different conditions: A review.
The release of metallic ions from orthodontic brackets and wires typically depends on their quality (chemical composition) and the medium to which they are exposed, e.g., acidic, alkaline, substances with a high fluoride concentration, etc. This review examines corrosion and wear of orthodontic brackets, wires, and arches exposed to different media, including: beverages (juices), mouthwashes and artificial saliva among others, and the possible health effects resulting from the release of metallic ions under various conditions. This review aims to determine the exposure conditions that cause the most wear on orthodontic devices, as well as the possible health effects that can be caused by the release of metallic ions under various conditions. A search was carried out in the Scopus database, for articles related to oral media that can corrode brackets and wires. The initial research resulted in 8,127 documents, after applying inclusion and exclusion criteria, 76 articles remained. Stainless steel, which is commonly used in orthodontic devices, is the material that suffers the most wear. It was also found that acidic pH, alcohols, fluorides, and chlorides worsen orthodontic material corrosion. Further, nickel released from brackets and wires can cause allergic reactions and gingival overgrowth into patients.


PAX5 fusion genes are frequent in poor risk childhood acute lymphoblastic leukaemia and can be targeted with BIBF1120.
Despite intensive risk-based treatment protocols, 15% of paediatric patients with B-Cell Precursor Acute Lymphoblastic Leukaemia (BCP-ALL) experience relapse. There is urgent need of novel strategies to target poor prognosis subgroups, like PAX5 translocated. We considered 289 childhood BCP-ALL cases consecutively enrolled in Italy in the AIEOP-BFM ALL2000/R2006 protocols and we performed extensive molecular profiling, integrating gene expression, copy number analyses and fusion genes discovery by target-capture NGS. We developed preclinical strategies to target PAX5 fusion genes. We identified 135 cases without recurrent genetic rearrangements. Among them, 59 patients (43·7%) had a Ph-like signature; the remaining cases were identified as ERG-related (26%), High-Hyperdiploid-like (17%), ETV6::RUNX1-like (8·9%), MEF2D-rearranged (2·2%) or KMT2A-like (1·5%). A poor prognosis was associated with the Ph-like signature, independently from other high-risk features. Interestingly, PAX5 was altered in 54·4% of Ph-like compared to 16·2% of non-Ph-like cases, with 7 patients carrying PAX5 fusions (PAX5t), involving either novel (ALDH18A1, IKZF1, CDH13) or known (FBRSL1, AUTS2, DACH2) partner genes. PAX5t cases have a specific driver activity signature, extending to multiple pathways including LCK hyperactivation. Among FDA-approved drugs and inhibitors, we selected Dasatinib, Bosutinib and Foretinib, in addition to Nintedanib, known to be LCK ligands. We demonstrated the efficacy of the LCK-inhibitor BIBF1120/Nintedanib, as single agent or in combination with conventional chemotherapy, both ex vivo and in patient-derived xenograft model, showing a synergistic effect with dexamethasone. This study provides new insights in high-risk Ph-like leukaemia and identifies a potential therapy for targeting PAX5-fusion poor risk group. Ricerca Finalizzata-Giovani Ricercatori (Italian Ministry of Health), AIRC, Transcall, Fondazione Cariparo.


Type of diabetes and waist-hip ratio are important determinants of serum lipoprotein (a) levels in diabetic patients.
This cross-sectional study compared serum lipoprotein (a) [Lp(a)] concentrations in type 1 and type 2 diabetic subjects and examined the determinants of Lp(a) concentrations in both types of diabetes. Serum Lp(a) was measured in 26 type 1 and 107 type 2 diabetic patients and 126 non-diabetic controls. HbA(1c), fasting lipids and urinary albumin were also assayed. Lp(a) concentrations were higher in both type 1 and type 2 diabetic patients compared with controls (P<0.0001 and P<0.0001, respectively), and were higher in type 1 than type 2 diabetic patients (P<0.05). Waist-hip ratio (WHR) was an independent determinant of Lp(a) concentrations in both type 1 and type 2 diabetes.


Effect ofTrichoderma species on growth of Fusariumproliferatiom and production of fumonisins, fusaproliferin and beauvericin.
Trichoderma species has been suggested as potential biocontrol agent forFusarium verticillioides on maize. In this cereal,F. verticillioides and F. proliferatum contributed to fumonisin accumulation. In addition,F. proliferatum could produce beauvericin and fusaproliferin.The aim of this work was to evaluate the effect ofTrichoderma spp. on growth and fumonisin B(1) fusaproliferin and beauvericin production byF. proliferatum.Dual cultures of F.proliferatum andT. harzianum ITEM 3636 andT. longibrachiatum ITEM 3635 on maize meal agar at 0.995 aw were done. The effect ofTrichoderma spp. on the lineal growth ofF. proliferatum was determined. The effect ofTrichoderma species on fumonisin B(1), fusaproliferin and beauvericin production byF. proliferatum was determined on co-inoculated maize kernels by HPLC.T. harzianum suppressedF. proliferatum growth once contact between the colonies occurred.T. longibrachiatum showed a less antagonistic effect againstF. proliferatum. A reduction on fumonisin B(1) production of 98% and 88% was observed in the co-incubation ofF. proliferatum withT. harzianum andT. longibrachiatum, respectively. The decrease of FB(1) production was significant even in maize kernels on whichF. proliferatum had been growing 7 days prior to the addition ofTrichoderma spp. The concentration of beauvericin and fusaproliferin produced during 30 days coincubation ofF. proliferatum with bothTrichoderma spp. did not differ to those produced byF. proliferatum alone. These mycotoxins might enter the food chain causing so far unknown consequences to the health of domestic animals and humans. For this reason it is important, when a potential biocontrol agent is under study, to test the effect on the fungal growth and on the putative mycotoxin produced.


Bifidobacterium lactis TY-S01 protects against alcoholic liver injury in mice by regulating intestinal barrier function and gut microbiota.
Alcohol-induced liver injury poses a significant threat to human health. Probiotics have been proven to prevent and treat alcohol-induced liver injury. In this study, the preventive effect of Bifidobacterium lactis TY-S01 on alcohol-induced liver injury in mice was investigated. TY-S01 pretreatment effectively protected mice against alcohol-induced liver injury by preserving the levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, triglyceride and high-density lipoprotein-cholesterol in serum and maintaining the levels of the inflammatory cytokines tumor necrosis factor-α, interleukin-6 and interleukin-1β in liver tissue. Additionally, TY-S01 could maintain the endotoxin levels in serum, maintain the mRNA expression levels of zonula occluden-1, occludin, claudin-1 and claudin-3 in the gut, and prevent gut microbiota dysbiosis in mice with alcoholic liver injury. Spearman's correlation analysis revealed that there was a clear correlation among serum indicators, inflammatory cytokines and gut microbiota. In conclusion, TY-S01 attenuates alcohol-induced liver injury by protecting the integrity of the intestinal barrier and maintaining the balance of the gut microbiota.


Trapping Tribbles: Nanobody-assisted structure of the TRIB2 pseudokinase.
TRIB2, a member of the human Tribbles pseudokinase family, functions as a molecular scaffold in diverse signaling pathways. In this issue of Structure, Jamieson et al. report the first high-resolution structure of TRIB2 bound to a nanobody that offers insights into its "active-like" state.


Is There an Impact of Concomitant Injuries and Timing of Fixation of Major Fractures on Fracture Healing? A Focused Review of Clinical and Experimental Evidence.
This review aims to summarize current knowledge regarding the underlying patho-mechanisms of delayed fracture healing in polytraumatized patients. The following search terms were used: "fracture", "hemorrhage," "chest trauma," "inflammation," "inflammatory response," "fracture healing," "delayed healing," "nonunion," "fracture stabilisation," "intramedullary nailing," "external fixation," "early total care," and "damage control." Medline, Embase, and Cochrane Library were searched for studies published between January 1, 1990 through March 30, 2014. Of 1322 publications, 68 were included in the current summary. Concomitant injuries and the strategy for fracture stabilization seem to affect bone metabolism and fracture healing. Among the relevant patho-mechanisms, interactions between the local and systemic inflammatory response seem to play a role. However, the consequences of fracture fixation strategies in case of severe concomitant injuries on local inflammation and bone healing remain unknown. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Fracture nonunion in long bones: A literature review of risk factors and surgical management.
Nonunion following a long bone fracture causes considerable morbidity when it occurs. Risk factors depend on specific fractures but there is a complex interplay of injury severity, comorbidities, patient medication and infection. The majority of nonunions occur after long bone fractures with the tibia, femur, forearm, humerus and clavicle predominating. Despite interest in the biological augmentation of fracture healing, the majority of nonunions can be effectively managed with conventional surgical techniques. In this review we present a review of risk factors for nonunion and the outcome following surgical management.


T-DNA alleles of the receptor kinase THESEUS1 with opposing effects on cell wall integrity signaling.
Perturbation of cellulose synthesis in plants triggers stress responses, including growth retardation, mediated by the cell wall integrity-sensing receptor-like kinase (RLK) THESEUS1 (THE1). The analysis of two alleles carrying T-DNA insertions at comparable positions has led to conflicting conclusions concerning the impact of THE1 signaling on growth. Here we confirm that, unlike the1-3 and other the1 alleles in which cellular responses to genetic or pharmacological inhibition of cellulose synthesis are attenuated, the1-4 showed enhanced responses, including growth inhibition, ectopic lignification, and stress gene expression. Both the1-3 and the1-4 express a transcript encoding a predicted membrane-associated truncated protein lacking the kinase domain. However, the1-3, in contrast to the1-4, strongly expresses antisense transcripts, which are expected to prevent the expression of the truncated protein as suggested by the genetic interactions between the two alleles. Seedlings overexpressing such a truncated protein react to isoxaben treatment similarly to the1-4 and the full-length THE overexpressor. We conclude that the1-4 is a hypermorphic allele; that THE1 signaling upon cell wall damage has a negative impact on cell expansion; and that caution is required when interpreting the phenotypic effects of T-DNA insertions in RLK genes.


Knowledge of AIDS transmission, risk behavior, and perceptions of risk among urban, low-income, African-American and Hispanic youth.
Low-income, urban, African-American and Hispanic youth have been identified as a group that may be at risk for the spread of human immunodeficiency virus (HIV). This article evaluates general knowledge of acquired immunodeficiency syndrome (AIDS), knowledge of routes of sexual transmission of HIV, risk behaviors related to sex, and perceived susceptibility to AIDS of urban low-income youth in Detroit. We drew data from a household probability sample of 1,435 of these Detroit youth. The data indicate that, with a few exceptions, general knowledge of AIDS and routes of sexual HIV transmission was good; there were small ethnic and gender differences in knowledge. However, we found substantial ethnic and gender differences in risk behaviors. Young African-American men reported the earliest initiation of sexual activity and the most partners. Young Hispanic women reported the latest initiation of sexual activity and the fewest partners. A substantial minority of the youth were concerned about becoming infected with HIV, and these concerns were related to risk behavior. We demonstrate from these data a need for interventions in this population to correct misconceptions and to promote use of condoms and other safer sexual behaviors.


Handedness and cognitive function in older men and women: a comparison of methods.
Previous studies of handedness and cognitive function rely on self-classification and yield inconsistent results. This study examines the associations of self-reported versus grip-strength-based handedness with cognitive function in healthy older men and women. Cross-sectional study. 1988-91 follow-up clinic visit and 1991 mailed survey. 684 men and 985 women aged 55-95 who were community dwelling. Cognitive function was assessed with 12 tests and grip strength was measured by hand-held dynamometer. Self-reported handedness was obtained with a mailed survey. By self-report, 92.1% of men and women were right-handed; 2.0% were left handed. By grip strength, in men, 64.3% were right-handed, 22.5% left-handed, and 13.2% ambidextrous. In women, 61.3% were right-handed, 17.3% left-handed, and 21.4% ambidextrous. No cognitive function differences were found by self-reported handedness in either sex (p's>0.10). However, based on grip strength, left-handed women scored poorer than right-handed or ambidextrous women in immediate and delayed memory, attention, and verbal fluency (p's<0.05). Using categorical definitions, left-handed or ambidextrous individuals based on grip strength were more likely to show poor cognitive function on 4 of 5 tests. Grip strength is a useful alternative to self-reports for classifying handedness. Left-handedness by grip-strength, may be related to poorer cognitive function; this association may vary by gender.


Quantitative determination of regional extravascular lung water and regional blood volume in congestive heart failure.
Regional extravascular lung water (rELW) and blood volume (rBV) in five controls and 14 patients with congestive heart failure (CHF) were measured by constant infusion of H215O and inhalation of 11CO using positron emission tomography (PET). The analysis of 18 regions per patient revealed a relatively homogeneous level of rELW in the controls (mean = 0.11 +/- 0.02 g/cc; range, 0.08-0.21), whereas this increase in patients with CHF (0.17 +/- 0.02 g/cc; range, 0.10-0.51). The rBV was 0.21 +/- 0.02 g/cc in the controls and 0.17 +/- 0.02 g/cc in patients with CHF. A good correlation was found between the severity of chronic heart failure (according to the grading of the New York Heart Association) and mean extravascular lung water (ELW) (r = 0.69), as well as between CHF and the ratio rELW/rBV (r = 0.87); however, the correlation to hemodynamic data was less satisfactory (cardiac index, r = 0.45; pulmonary capillary wedge pressure, r = 0.47; ejection fraction, r = 0.60). In supine controls, a progressive decrease in regional blood volume from the basal to the apical regions was observed, whereas the differences in ELW were only small. In patients with chronic heart failure, ELW in the basal parts was markedly increased, whereas in the apical regions, only minor deviations from the controls were observed. In the basal regions of these patients, the blood volume was reduced by about 30%. Instead of the normal basoapical gradient of blood volume, these patients showed a rather flat distribution. Radiographic findings of pulmonary edema generally appeared together with an ELW level of greater than 0.14 g/cc.(ABSTRACT TRUNCATED AT 250 WORDS)


Motivation to seek psychotherapy in patients with recurrent depressive disorder.
Fifty-five hospital-treated patients with the ICD-10 diagnosis of recurrent depressive episode(s) were classified according to the Newcastle Depressive Diagnostic Scale as having either psychogenic (n = 25) or endogenous (n = 30) depression and interviewed using the Composite International Diagnostic Interview and the Questionnaire for Assessment of Motivation to Seek Psychotherapy. The two groups were found to differ significantly from one another in two Motivation to Seek Psychotherapy subscales ("layman's etiology" and "general expectations from therapy"). The motivation to seek psychotherapy was greater in patients with psychogenic depression than in patients with endogenous depression. Nonetheless, psychotherapy is indispensable in treating endogenous depression, especially for patients under situational stress or at risk of suicide.


Analysis of formaldehyde and acrolein in the aqueous samples using a novel needle trap device containing nanoporous silica aerogel sorbent.
In this research, a needle trap device (NTD) packed with nanoporous silica aerogel as a sorbent was used as a new technique for sampling and analysis of formaldehyde and acrolein compounds in aqueous and urine samples. The obtained results were compared with those of the commercial sorbent Carboxen1000. Active sampling was used and a 21-G needle was applied for extraction of gas in the sample headspace. The optimization of experimental parameters like salt addition, temperature and desorption time was done and the performance of the NTD for the extraction of the compounds was evaluated. The optimum temperature and time of desorption were 280 °C and 2 min, respectively. The ranges of limit of detection, limit of quantification and relative standard deviation (RSD) were 0.01-0.03 μg L-1, 0.03-0.1 μg L-1 and 2.8-7.3%, respectively. It was found that the NTD containing nanoporous silica aerogel had a better performance. Thus, this technique can be applied as an effective and reliable method for sampling and analysis of aldehyde compounds from different biological matrices like urine, exhalation and so on.


High performance liquid chromatography for the simultaneous analysis of penicillin residues in beef and milk using ion-paired extraction and binary water-acetonitrile mixture.
An ion-paired extraction (IPE) has been developed for the analysis of penicillin antibiotics (penicillin G, oxacillin and cloxacillin) in beef and milk samples using tetrabutylammonium bromide (TBABr) as ion-pairing agent and binary water-acetonitrile as extractant. The factors affecting the IPE efficiency were optimized including solution pH, volume of acetonitrile (ACN), concentration of TBABr and electrolyte salt (NH(4))(2)SO(4). The optimum IPE conditions were 10 mmol L(-1) phosphate buffer pH 8, 2 mL of ACN, 6 mmol L(-1) of TBABr and 2.5 mL of saturated ammonium sulfate. Under the HPLC condition: an Xbridge™ C18 reversed-phase column, isocratic elution of 5 mmol L(-1) phosphate buffer (pH 6.6) and acetonitrile (75:25, v/v) and a flow rate of 1 mL min(-1), with UV detection at 215 nm, the separation of three penicillins was achieved within 10 min. Under the selected optimum conditions, the enhancement of 21-53 folds compared to that without preconcentration and limits of detection (LODs) of 1-2 ng mL(-1) were obtained. Good reproducibility was achieved with RSD<2% for retention time and <5% for slope of calibration curves. The average recoveries higher than 85% were obtained. The proposed IPE-HPLC method has shown to be high efficient preconcentration and analysis method for penicillin residues in beef and milk with LOD lower than the maximum residue limits.


Microwave-assisted synthesis of deuterium labeled estrogen fatty acid esters.
Deuterated analogs of estrogen fatty acid esters are needed as internal standards for isotope dilution GC/MS analyses. We have developed a rapid and efficient synthesis for 2,4,16,16-D4-estrone palmitate, stearate, oleate, linoleate, and linolenate and the corresponding 2,4,16,16,17alpha-D5-estradiol fatty acid 17-mono and 3,17-diesters using analogous fatty acid chlorides or fatty acid anhydrides and 4-(dimethylamino)pyridine under microwave irradiation. Chemoselective hydrolysis of fatty acid diesters was carried out by KOH in t-BuOH.


Tipping points, thresholds and the keystone role of physiology in marine climate change research.
The ongoing and future effects of global climate change on natural and human-managed ecosystems have led to a renewed interest in the concept of ecological thresholds or tipping points. While generalizations such as poleward range shifts serve as a useful heuristic framework to understand the overall ecological impacts of climate change, sophisticated approaches to management require spatially and temporally explicit predictions that move beyond these oversimplified models. Most approaches to studying ecological thresholds in marine ecosystems tend to focus on populations, or on non-linearities in physical drivers. Here we argue that many of the observed thresholds observed at community and ecosystem levels can potentially be explained as the product of non-linearities that occur at three scales: (a) the mechanisms by which individual organisms interact with their ambient habitat, (b) the non-linear relationship between organismal physiological performance and variables such as body temperature and (c) the indirect effects of physiological stress on species interactions such as competition and predation. We explore examples at each of these scales in detail and explain why a failure to consider these non-linearities - many of which can be counterintuitive - can lead to Type II errors (a failure to predict significant ecological responses to climate change). Specifically, we examine why ecological thresholds can occur well before concomitant thresholds in physical drivers are observed, i.e. how even small linear changes in the physical environment can lead to ecological tipping points. We advocate for an integrated framework that combines biophysical, ecological and physiological methods to generate hypotheses that can be tested using experimental manipulation as well as hindcasting and nowcasting of observed change, on a spatially and temporally explicit basis.


Mucoid cytoplasmic inclusions in urothelial carcinomas.
To date, mucoid cytoplasmic inclusions in urothelial carcinomas have rarely been noted. However, we were impressed by the fact that these corpuscles are readily detectable in numerous urothelial neoplasms. Therefore, a histologic analysis of 100 cases of urothelial carcinomas was performed. Overall, 37 cases revealed periodic acid-Schiff-positive cytoplasmic inclusions. These were observed in 14% of grade 1, 49% of grade 2, and 63% of grade 3 carcinomas. The inclusions were histochemically, immunohistochemically, and ultrastructurally identified as cytoplasmic deposits of mucoid materials. Two types of deposits, condensed and noncondensed, could be distinguished. The demonstration of mucoid deposits in otherwise poorly differentiated metastatic carcinomas may be of some differential diagnostic importance insofar as urothelial carcinoma has to be considered as the possible primary tumor.


Cytokine induction by purified lipoteichoic acids from various bacterial species--role of LBP, sCD14, CD14 and failure to induce IL-12 and subsequent IFN-gamma release.
We have recently shown that highly purified lipoteichoic acid (LTA) represents a major immunostimulatory principle of Staphylococcus aureus. In order to test whether this translates to other bacterial species, we extracted and purified LTA from 12 laboratory-grown species. All LTA induced the release of TNF-alpha, IL-1beta, IL-6 and IL-10 in human whole blood. Soluble CD14 (sCD14) inhibited monokine induction by LTA but failed to confer LTA responsiveness for IL-6 and IL-8 release of human umbilical vein endothelial cells (HUVEC). In a competitive LPS-binding protein (LBP) binding assay, the IC(50) of the tested LTA preparations was up to 3,230-fold higher than for LPS. LBP enhanced TNF-alpha release of human peripheral blood mononuclear cells (PBMC) upon LPS but not LTA stimulation. These data demonstrate a differential role for the serum proteins LBP and sCD14 in the recognition of LPS and LTA. Different efficacies of various anti-CD14 antibodies against LPS vs. LTA-induced cytokine release suggest that the recognition sites of CD14 for LPS and LTA are distinct with a partial overlap. While the maximal achievable monokine release in response to LTA was comparable to LPS, all LTA induced significantly less IL-12 and IFN-gamma. IL-12 substitution increased LTA-inducible IFN-gamma release up to 180-fold, suggesting a critical role of poor LTA-inducible IL-12 for IFN-gamma formation. Pretreatment with IFN-gamma rendered galactosamine-sensitized mice sensitive to challenge with LTA. In conclusion, LTA compared to LPS, are weak inducers of IL-12 and subsequent IFN-gamma formation which might explain their lower toxicity in vivo.


Maternal hepatitis B virus and hepatitis C virus carrier status during pregnancy and long-term respiratory complications in the offspring.
Maternal HBV or HCV carrier status is a cause for concern regarding both the course of pregnancy and the short-term perinatal outcomes. Our main aim was to evaluate whether offspring born to carrier mothers during pregnancy, also suffer from long-term pediatric respiratory morbidity (until 18 years of age). A population-based cohort analysis was conducted at a single tertiary medical center. The study included all singleton deliveries between the years 1991-2014, comparing incidence of respiratory-related hospitalization of offspring born to mothers who were carrier of HBV or HCV during their pregnancy to those born to nonexposed mothers. Respiratory morbidities were based on a predefined set of ICD-9 codes. A Kaplan-Meier survival curve was used to compare cumulative hospitalization incidence between the groups and a Cox regression model was used to adjust for confounding variables. During the study period, 242,342 deliveries met the inclusion criteria. Of them, 771 (0.31%) were to HBV or HCV mother carriers during pregnancy. A Kaplan-Meier curve demonstrated that children born to HBV or HCV carriers had higher cumulative incidence of respiratory morbidity (Log rank test p = 0.007). In the Cox regression model, while controlling for maternal age, diabetes mellitus, hypertensive disorders, caesarian section and gestational age at birth, maternal HBV or HCV carrier status was noted as an independent risk factor for long-term respiratory morbidity in the offspring (adjusted HR = 1.43, 95% CI 1.07-1.90, p = 0.015). Maternal HBV or HCV carrier status in pregnancy may increase offspring susceptibility to long-term respiratory morbidity.


Postoperative wound infection.
Three clinicians review the work of Cruse and Foord, cited below, and discuss its effect on current and future practice.


A six-year study of the Omniscience valve in four Canadian centers.
Stimulated by the recent controversy over the Omniscience valve, we conducted a follow-up study on 413 hospital survivors in whom this prosthesis was implanted at four Canadian centers from 1979 to 1985. One hundred forty-seven underwent aortic valve replacement (AVR), 203 had mitral valve replacement (MVR), 10 had tricuspid valve replacement (TVR) and 53 underwent multiple valve replacement (45 AVR + MVR, 5 MVR + TVR, and 3 AVR + MVR + TVR). The mean age was 50.8 +/- 13 years (range, 2 months to 75 years). Follow-up of 96% was achieved for a mean of 2.6 years and a maximum of 6 years with a total of 1,076 patient-years. Complications were defined and graded according to severity. Analyses were performed to yield linearized and actuarial rates for complications. There were 30 late deaths (2.8% per patient-year). At 5 years, the actuarial survival was 89 +/- 3% (AVR, 89 +/- 3% and MVR, 91 +/- 3%). Percentages for freedom from each complication are as follows: endocarditis, 96 +/- 1% (AVR, 96 +/- 2% and MVR, 98 +/- 1%); periprosthetic leak, 99 +/- 0.6% (AVR, 98 +/- 1% and MVR, 99 +/- 0.6%); thrombotic complications, 87 +/- 3% (AVR, 84 +/- 6% and MVR, 90 +/- 3%); valve thrombosis 99.4% (AVR and MVR, 100%); anti-coagulant-related hemorrhage, 94 +/- 2% (AVR, 97 +/- 2% and MVR, 94 +/- 2%); and all valve-related complications, 77 +/- 3% (AVR, 77 +/- 6% and MVR, 79 +/- 4%). Reoperation was required at the rate of 1.2% per patient-year.(ABSTRACT TRUNCATED AT 250 WORDS)


A 400-Gb/s WDM-PAM4 OWC system through the free-space transmission with a water-air-water link.
A 400-Gb/s wavelength-division-multiplexing (WDM) four-level pulse amplitude modulation (PAM4) optical wireless communication (OWC) system through a 200-m free-space transmission with either an 8.8-m piped water-air-piped water link or a 6.5-m turbid water-air-turbid water link is successfully constructed. Incorporating PAM4 modulation with an 8-wavelength WDM scheme greatly increases the total transmission rate of the WDM-PAM4 OWC system to 400 Gb/s (50 Gb/s/λ × 8 λs). By adopting doublet lenses in free-space transmission, a laser beam reducer/expander and a reflective spatial light modulator (SLM) with an angle expander through the water-air-water link, good bit error rate performance and acceptable PAM4 eye diagrams are obtained. Using a reflective SLM with an angle expander not only adaptively adjusts the laser beam, but also effectively solves the oceanic engineering problems. This demonstrates WDM-PAM4 OWC system outperforms existing OWC systems through the free-space transmission with an air-water-air link because it can solve the practical engineering problems in actual oceanic environments.


The Age of Next-Generation Therapeutic-Microbe Discovery: Exploiting Microbe-Microbe and Host-Microbe Interactions for Disease Prevention.
Humans are considered "superorganisms," harboring a diverse microbial collective that outnumbers human cells 10 to 1. Complex and gravely understudied host- and microbe-microbe interactions-the product of millions of years of host-microbe coevolution-govern the superorganism in almost every aspect of life functions and overall well-being. Abruptly disrupting these interactions via extrinsic factors has undesirable consequences for the host. On the other hand, supplementing commensal or beneficial microbes may mitigate perturbed interactions or enhance the interactive relationships that ultimately benefit all parties. Hence, immense efforts have focused on dissecting the innumerable host- and microbe-microbe relationships to characterize if a "positive" or "negative" interaction is at play and to exploit such behavior for broader implications. For example, microbiome research has worked to identify and isolate naturally antipathogenic microbes that may offer therapeutic potential either in a direct, one-on-one application or by leveraging its unique metabolic properties. However, the discovery and isolation of such desired therapeutic microbes from complex microbiota have proven challenging. Currently, there is no conventional technique to universally and functionally screen for these microbes. With this said, we first describe in this review the historical (probiotics) and current (fecal microbiota or defined consortia) perspectives on therapeutic microbes, present the discoveries of therapeutic microbes through exploiting microbe-microbe and host-microbe interactions, and detail our team's efforts in discovering therapeutic microbes via our novel microbiome screening platform. We conclude this minireview by briefly discussing challenges and possible solutions with therapeutic microbes' applications and paths ahead for discovery.


Physicochemical properties, degradation kinetics, and antioxidant capacity of aqueous anthocyanin-based extracts from purple carrots compared to synthetic and natural food colorants.
As a means to evaluate the potential of carrot anthocyanins as food colorants and nutraceutical agents, we investigated the physicochemical stability and antioxidant capacity of purple carrot extracts under different pH (2.5-7.0) and temperature (4-40 °C) conditions, in comparison to a commercial synthetic (E131) and a natural grape-based (GRP) colorant. During incubation, the colorants were weekly-monitored for various color parameters, concentration of anthocyanins and phenolics, and antioxidant capacity. Carrot colorants were more stable than GRP; and their thermal stability was equal (at 4 °C) or higher than that of E131 (at 25-40 °C). Carrot anthocyanins had lower degradation rate at low pH and temperature, with acylated anthocyanins (AA) being significantly more stable than non-acylated anthocyanins (NAA). Anthocyanins acylated with feruloyl and coumaroyl glycosides were the most stable carrot pigments. The higher stability of carrot colorants is likely due to their richness in AA and -to a lesser extent- copigmentation with other phenolics.


Misplacement of nasogastric tubes and oesophageal monitoring devices.
Accidental invasion of the trachea past an inflated cuff may occur more easily when endotracheal tubes with soft, low pressure cuffs are used. A new, simple and safe technique for blind oesophageal intubation is outlined. Two cases of accidental invasion of the trachea by oesophageal tubes are described.


Proteome changes in rat serum after a chronic ingestion of enriched uranium: Toward a biological signature of internal contamination and radiological effect.
The civilian and military use of uranium results in an increased risk of human exposure. The toxicity of uranium results from both its chemical and radiological properties that vary with isotopic composition. Validated biomarkers of health effects associated with exposure to uranium are neither sensitive nor specific to uranium radiotoxicity and/or radiological effect. This study aimed at investigating if serum proteins could be useful as biomarkers of both uranium exposure and radiological effect. Male Sprague-Dawley rats were chronically exposed through drinking water to low levels (40mg/L, corresponding to 1mg of uranium per animal per day) of either 4% (235)U-enriched uranium (EU) or 12% EU during 6 weeks. A proteomics approach based on two-dimensional electrophoresis (2D-DIGE) and mass spectrometry (MS) was used to establish protein expression profiles that could be relevant for discriminating between groups, and to identify some differentially expressed proteins following uranium ingestion. It demonstrated that the expressions of 174 protein spots over 1045 quantified spots were altered after uranium exposure (p<0.05). Using both inferential and non-supervised multivariate statistics, we show sets of spots features that lead to a clear discrimination between controls and EU exposed groups on the one hand (21 spots), and between 4% EU and 12% EU on the other hand (7 spots), showing that investigation of the serum proteome may possibly be of relevance to address both uranium contamination and radiological effect. Finally, using bioinformatics tools, pathway analyses of differentially expressed MS-identified proteins find that acute phase, inflammatory and immune responses as well as oxidative stress are likely involved in the response to contamination, suggesting a physiological perturbation, but that does not necessarily lead to a toxic effect.


Systematic identification of chemical components in Fufang Shuanghua oral liquid and screening of potential active components against SARS-CoV-2 protease.
Coronavirus disease (COVID-19) caused by SARS-COV-2 infection has been widely prevalent in many countries and has become a common challenge facing mankind. Traditional Chinese medicine (TCM) has played a prominent role in this pandemic, and especially TCM with the function of "heat-clearing and detoxifying" has shown an excellent role in anti-virus. Fufang Shuanghua oral liquid (FFSH) has been used to treat the corresponding symptoms of influenza such as fever, nasal congestion, runny nose, sore throat, and upper respiratory tract infections in clinic, which are typical symptoms of COVID-19. The content of chlorogenic acid, andrographolide and dehydrated andrographolide as the quality control components of FFSH is not less than 1.0 mg/mL, 60 μg/mL and 60 μg/mL respectively. In this study, UPLC-Q-TOF-MS/MS was employed to describe the chemical profile of FFSH. Virtual screening and fluorescence resonance energy transfer (FRET) were used to screen the effective components of FFSH acting on SARS-CoV-2 main protease (Mpro). As a result, 214 compounds in FFSH were identified or preliminarily characterized by UPLC-Q-TOF-MS/MS, and 61 active ingredients with potential inhibitory effects on Mpro were selected through receptor-based and ligand-based virtual screening. In particular, quercetin, forsythoside A, and linoleic acid showed a good inhibitory effect on Mpro in FRET evaluation with IC50 values of 26.15 μM, 22.26 μM and 47.09 μM respectively, and had a strong binding affinity with the receptor Mpro (6LU7) in molecular docking. CYS145 and HIS41 were the main amino acid residues affected by small molecules in the protein binding domain. In brief, we characterized, for the first time, 214 chemical components in FFSH, and three of them, including quercetin, forsythoside A and linoleic acid, were screened out to exert beneficial anti-COVID-19 effects through CYS145 and HIS41 sites, which may provide a new research strategy for TCM to develop new therapeutic drugs against COVID-19.


Histology-specific FGFR2 alterations and FGFR2-TACC2 fusion in mixed adenoid cystic and neuroendocrine small cell carcinoma of the uterine cervix.
Neuroendocrine small cell carcinoma of the uterine cervix portends a dismal prognosis with limited treatment options. Rarely, tumors of mixed-lineage appear in gynecologic malignancies. Here, we report a 77-year-old woman who presented with complete uterine prolapse and 4-month history of vaginal bleeding. Histopathologic evaluation revealed a mixed adenoid cystic carcinoma and neuroendocrine small cell carcinoma of the uterine cervix. The tumor was PD-L1 and HPV 35 positive. The patient was treated with up-front surgery and adjuvant radiation. Independent, histology-specific alterations in FGFR2 and a FGFR2-TACC2 fusion were identified. Progression of disease occurred within 6 months for which she received chemotherapy and immunotherapy. However, the patient expired within a year. We comprehensively review how screening for and targeting of FGFR alterations in recurrent and metastatic cervical cancer might serve as a touchstone for future treatment regimens.


Molecular Design Principles for Ferroelectrics: Ferroelectrochemistry.
Ferroelectric materials have a variety of technological applications, as transducers, capacitors, sensors, etc. Great interest in molecular ferroelectrics has emerged because of their structural flexibility, tunability, and homochirality. However, the discoveries of molecular ferroelectrics are not abundant. The lack of chemical design is the main challenge in realizing new molecular ferroelectrics. Consequently, chemical design approaches, including the ideas of introducing quasi-spherical theory, homochirality, and H/F substitution, have been developed recently. Through these advanced methodologies, a wide range of ferroelectrics were successfully synthesized, changing the blind search into a targeted chemical design. In this Perspective, we aim to provide insight into the fundamental chemistry and physics of molecular ferroelectrics and propose the concept of "ferroelectrochemistry", concerned with the targeted design and performance optimization of molecular ferroelectrics from the chemical point of view. We start with the basic theories used in the modification of chemical structures for new molecular ferroelectrics, such as the quasi-spherical theory. After that, we focus on the fundamentals of homochirality from the perspective of chemistry and advantages of introducing a homochiral molecule within the scope of ferroelectrics. Further, we explore another design strategy, H/F substitution, as an analogue of the H/D isotope effect. The introduction of a F atom usually does not change the polar point group but may induce a minor structural disruption that enhances physical properties such as Curie temperature and spontaneous polarization. We hope our comprehensive studies on the targeted design and performance optimization strategies for molecular ferroelectrics may build up and enrich the content of ferroelectrochemistry.


Increased chitin biosynthesis contributes to the resistance of Penicillium polonicum against the antifungal protein PgAFP.
Antifungal proteins from molds have been proposed as a valuable tool against unwanted molds, but the resistance of some fungi limits their use. Resistance to antimicrobial peptides has been suggested to be due to lack of interaction with the mold or to a successful response. The antifungal protein PgAFP produced by Penicillium chrysogenum inhibits the growth of various ascomycetes, but not Penicillium polonicum. To study the basis for resistance to this antifungal protein, localization of PgAFP and metabolic, structural, and morphological changes were investigated in P. polonicum. PgAFP bound the outer layer of P. polonicum but not regenerated chitin, suggesting an interaction with specific molecules. Comparative two-dimensional gel electrophoresis (2D-PAGE) and comparative quantitative proteomics revealed changes in the relative abundance of several proteins from ribosome, spliceosome, metabolic, and biosynthesis of secondary metabolite pathways. The proteome changes and an altered permeability reveal an active reaction of P. polonicum to PgAFP. The successful response of the resistant mold seems to be based on the higher abundance of protein Rho GTPase Rho1 that would lead to the increased chitin deposition via cell wall integrity (CWI) signaling pathway. Thus, combined treatment with chitinases could provide a complementary means to combat resistance to antifungal proteins.


Keeping quality of vacuum-packed smoked sardine fillets: microbiological aspects.
The effect of mixed smoking (2 h at 30 degrees C and 45 min at 75 degrees C was studied on the keeping quality of lean and fatty sardine fillets from fish caught in the Mediterranean Sea in March and June, respectively. Raw material for smoking included both fresh and frozen sardine fillets. Microbiological and sensory analyses were performed over the storage period, which lasted for 120 days at 0 +/- 1 degrees C. Smoking reduced the viable microbial flora values from 3-5 x 10(4) cfu/g to 2 x 10(2) cfu/g. The antimicrobial action of smoking, combined with that of vacuum packaging, had the effect of producing a gram-positive flora made up mainly of lactic acid bacteria. A practical consequence of this was to extend the shelf life of the smoked sardines for a period of 4 months. Frozen storage of samples at -18 degrees C for 6 months prior to smoking affected the behaviour of the microbial flora during cold storage at 0 degrees C, but did not affect the behaviour of the flora over a period of 3 months frozen storage, since the initial numbers of bacteria decreased and microbial growth was retarded. Furthermore, at the end of the storage period, the number of bacteria in the samples of frozen fatty sardines were higher than in the samples of frozen lean sardine. Physical conditions, therefore appear to exert an influence on bacterial growth. Sulphite-reducing Clostridia were not detected during the storage period.


Autochthonous Bacilli and Fructooligosaccharide as Functional Feed Additives Improve Growth, Feed Utilisation, Haemato-Immunological Parameters and Disease Resistance in Rohu, Labeo rohita (Hamilton).
The effects of Bacillus spp. (7 Log CFU g-1 feed) and fructooligosaccharide (FOS, 1%) as functional feed additives, either alone or in combination, were evaluated in a study on rohu, Labeo rohita fingerlings. The fish were fed different diets for 90 days, including a control diet and diets supplemented with FOS, B. licheniformis, B. methylotrophicus or synbiotic formulations of these. The results showed that the combination of B. licheniformis and FOS significantly improved weight gain, feed utilisation and protease activity compared to the other groups. Overall, the groups supplemented with probiotics and synbiotics (B. licheniformis + FOS or B. methylotrophicus + FOS) showed improvements in haematology, serum biochemistry and immune parameters compared to the control group. After 90 days of experimental feeding, the fish were challenged with pathogenic Aeromonas hydrophila, and data on haematology, immunity and stress parameters were collected. The results indicated that the application of Bacillus spp. and FOS boosted immunity and resistance to physiological stress in the fish. The highest post-challenge survival rate was observed in fish fed a diet with B. licheniformis and FOS, indicating the potential of this particular combination of functional feed additives to enhance growth, immunity and disease resistance in L. rohita.


Extracellular RNAs/TLR3 signaling contributes to acute intestinal injury induced by intestinal ischemia reperfusion in mice.
Toll-like receptor 3 (TLR3), one pattern recognition receptor activated by viral and endogenous RNA, has been recently reported to regulate ischemia/reperfusion (I/R) injury in various organs. However, the role of TLR3 in the development of intestinal I/R injury remains unclear. The aim of this study is to evaluate the effects of extracellular RNAs/TLR3 signaling in intestinal I/R injury. An intestinal I/R injury model was established with superior mesenteric artery occlusion both in wild-type and TLR3 knockout (KO, -/-) mice, and MODE-K cells were subjected to hypoxia/reoxygenation (H/R) to mimic the I/R model in vivo. Extracellular RNAs (exRNAs), especially double-stranded RNAs (dsRNAs) co-localized with TLR3, were significantly increased both in vitro and in vivo. Compared with wild-type mice, TLR3 knockout obviously attenuated intestinal I/R injury. Both TLR3/dsRNA complex inhibitor and TLR3 siRNA administration reduced TLR3 expressions and subsequently inhibited intestinal inflammatory cytokine production and apoptosis. In conclusion, exRNAs/TLR3 signaling is a key mechanism that regulates intestinal I/R injury in adult mice, and the TLR3/dsRNA complex inhibitor can be an effective approach for attenuating intestinal I/R-induced inflammatory response and apoptosis.


Enhanced effect of aggregated gold nanoparticles on luminol chemiluminescence system and its analytical application.
Some organic compounds containing groups of OH, NH2, or SH, which could induce the aggregation of gold nanoparticles (AuNPs), were observed to enhance effectively the luminol-H2O2-2.6 nm AuNPs CL system. It was found that the aggregation of AuNPs was an important effect factor for the catalytic activity of AuNPs on luminol CL system. The aggregated AuNPs could effectively enhance luminol CL signal compared with the dispersed one. The enhanced effect was closely related to the sizes of AuNPs. Among the studied AuNPs with seven sizes, 2.6 nm AuNPs had the greatest enhancement effect on luminol CL system after its aggregation. The CL enhancement mechanism was investigated, and the marked enhancement of aggregated 2.6 nm AuNPs for luminol CL system was supposed to originate from the decrease of AuNPs' surface negative charge density compared to its dispersed state. For the luminol-H2O2-2.6 nm AuNPs CL system in the presence of organic compounds containing groups of OH, NH2, or SH, more than one factor played the role in influencing the CL intensity. It was found that the enhanced effect of aggregated 2.6 nm AuNPs induced by such organic compounds was much more significant than the inhibition effect of reducing groups of OH, NH2, or SH, which made it applicable for the determination of this kind of compounds.


Transmembrane protein models based on high-throughput molecular dynamics simulations with experimental constraints.
Elucidating the structure of transmembrane proteins domains with high-resolution methods is a difficult and sometimes impossible task. Here, we explain the method of combining a limited amount of experimental data with automated high-throughput molecular dynamics (MD) simulations of alpha-helical transmembrane bundles in an explicit lipid bilayer/water environment. The procedure uses a systematic conformational search of the helix rotation with experimentally constrained MDs simulations. The experimentally determined helix tilt and rotational angle of a labeled residue with site-specific infrared dichroism allows us to select a unique high-resolution model from a number of possible energy minima encountered in the systematic conformational search.


Neuroinflammatory perspectives on the two faces of Alzheimer's disease.
The amyloid plaques in Alzheimer's disease (AD) brains are co-localized with a broad variety of inflammation-related proteins (complement factors, acute-phase proteins, pro-inflammatory cytokines) and clusters of activated microglia. The present data suggest that Abeta deposits in AD brains are closely associated with a locally induced, non-immune mediated, chronic inflammatory response. Clinicopathological and neuroradiological studies show that activation of microglia is a relatively early pathogenic event that precedes the process of neuropil destruction in AD. Epidemiological studies indicate that polymorphisms of certain cytokines and acute-phase proteins that are colocalized with Abeta plaques, are genetic risk factors of AD. Epidemiological studies have also shown that the use of classical nonsteroidal anti-inflammatory drugs (NSAIDs) can prevent the risk of AD but clinical trials with anti-inflammatory drugs in AD patients were negative. These findings indicate that anti-inflammatory agents can be helpful in the prevention but not in the treatment of AD. So, pathological, genetic and therapeutic studies suggest that inflammatory mechanisms are most likely involved in the early steps of the pathological cascade. In the autosomal dominant inherited forms of AD the primary factor is the increased production of Abeta1-42 resulting into fibrillar Abeta deposition that elicits a brain inflammatory response. The etiology of the sporadic forms is yet unknown but this subtype is considered to be heterogeneous and multifactorial in its pathogenesis. Here we review the evidence that inflammation related events could be a critical etiological factor in certain forms of the sporadic AD.


A case of segmental myoclonus in amputation stump: evidence for spinal generator and physiopathogenetic hypothesis.
We describe a 68-year-old woman who experienced pain and phantom limb sensation following an above-the-knee amputation of the right leg. A month later, the patient had myoclonic jerks of the stump. Polymyo-graphic recordings showed synchronous jerks in the vastus medialis and adductors of the thigh on the right side. The patient responded to clonazepam. We conclude that the myoclonic jerks were of spinal cord origin.


Insurance status and access to urgent ambulatory care follow-up appointments.
There is growing pressure to avoid hospitalizing emergency department patients who can be treated safely as outpatients, but this strategy depends on timely access to follow-up care. To determine the association between reported insurance status and access to follow-up appointments for serious conditions that are commonly identified during an emergency department visit. Eight research assistants called 499 randomly selected ambulatory clinics in 9 US cities (May 2002-February 2003) and identified themselves as new patients who had been seen in an emergency department and needed an urgent follow-up appointment (within 1 week) for 1 of 3 clinical vignettes (pneumonia, hypertension, or possible ectopic pregnancy). The same person called each clinic twice using the same clinical vignette but different insurance status. Proportion of callers who were offered an appointment within a week. Of 499 clinics contacted in the final sample, 430 completed the study protocol. Four hundred six (47.2%) of 860 total callers and 277 (64.4%) of 430 privately insured callers were offered appointments within a week. Callers who claimed to have private insurance were more likely to receive appointments than those who claimed to have Medicaid coverage (63.6% [147/231] vs 34.2% [79/231]; difference, 29.4 percentage points; 95% confidence interval, 21.2-37.6; P<.001). Callers reporting private insurance coverage had higher appointment rates than callers who reported that they were uninsured but offered to pay 20 dollars and arrange payment of the balance (65.3% [130/199] vs 25.1% [50/199]; difference, 40.2; 95% confidence interval, 31.4-49.1; P<.001). There were no differences in appointment rates between callers who claimed to have private insurance coverage and those who reportedly were uninsured but willing to pay cash for the entire visit fee (66.3% [132/199] vs 62.8% [125/199]; difference, 3.5; 95% confidence interval -3.7 to 10.8; P = .31). The median charge was 100 dollars (range, 25 dollars-600 dollars). Seventy-two percent of clinics did not attempt to determine the severity of the caller's condition. Reported insurance status is associated with access to timely follow-up ambulatory care for potentially serious conditions. Having private insurance and being willing to pay cash may not eliminate the difficulty in obtaining urgent follow-up appointments.


Efficacy and safety of a novel submucosal injection solution for endoscopic resection in porcine models.
A submucosal injection is usually required to improve the efficacy and safety of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). This study aimed to evaluate the performance of 3.3% sodium carboxymethyl starch (Na-CMS) solution, a novel submucosal injection solution, for ESD and EMR. Na-CMS, normal saline (NS) and two commercially available agents (sigMAVisc and Eleview) were injected into the esophageal submucosa of randomly grouped pigs. The level of submucosal elevation was examined. Subsequently, ESD or EMR procedures using 3.3% Na-CMS or NS as submucosal injections were performed in the gastrointestinal tract of the pigs. Submucosal elevation was significantly higher and more sustained in the 3.3% Na-CMS group than in the controls (P < 0.05). The volume required for ESD or EMR was significantly lower in the 3.3% Na-CMS group than in the NS group (ESD: 12.21 ± 4.09 mL vs 28.25 ± 8.02 mL, P < 0.001; EMR: 3.99 ± 1.98 mL vs 7.15 ± 3.67 mL, P = 0.001). The ESD resection time was significantly shorter in the 3.3% Na-CMS group than in the NS group (16.58 ± 7.30 min vs 25.29 ± 11.89 min, P = 0.004). Hemorrhage after ESD in the 3.3% Na-CMS group was less severe than that in the NS group (P = 0.006). 3.3% Na-CMS is an effective, safe and low-cost submucosal injection solution and holds promise as preferable agent for submucosal injection in ESD and EMR procedures.


Potable and irrigation suitability of different water supply systems in riverine communities at river Cauvery distributaries, India.
Current study focused on investigating the pollution loads of open well, bore well and drinking water from riverine community sites. In addition, drinking and irrigation suitability assessment were also performed by using user specific water quality indices (USWQI) and parameters quality index (PQI). Principal component analysis (PCA) was also performed with physio-chemical parameters. Notable variation was found in most of the water quality parameters at major hamlet and some places exceeded the standards prescribed by authorized organizations. The USWQI was 97.53 to 38.15 in open wells, 96.06 to 68.23 in bore wells, and 88.64 to 74.16 in tap water (drinking water). Among the settlement, highest water quality was recorded at Vilangudi, while the lowest quality found in Karaipakkam area. The predominant drinking water samples were estimated as good quality for human health and hygiene whereas none of the sample was found to be excellent. Open and bore well water samples were of good quality and suitable for agriculture purposes except the few samples which were estimated as poor and fair quality.


The role of growth hormone and insulin-like growth factor-1 in Crohn's disease: implications for therapeutic use of human growth hormone in pediatric patients.
This review evaluates the role of the growth hormone (GH) and insulin-like growth factor (IGF) in influencing linear growth in pediatric Crohn's disease. It also examines the current evidence concerning the use of recombinant human growth hormone (rhGH) as a potential therapy in achieving optimal growth and inducing mucosal healing for pediatric Crohn's disease. Current treatment strategies for Crohn's disease including antitumor necrosis factor-α (TNF-α) therapy have been demonstrated to improve growth velocity, but linear growth deficits persist despite optimization of therapy. By complex mechanisms, including the reduction of levels of IGF-1 and induction of systemic and hepatic GH resistance, cytokines such as TNF-α and interleukin-6 (IL-6), commonly elevated in active Crohn's disease, are important as mediators of linear growth delay. Recent evidence suggests that rhGH therapy is effective in improving short-term linear growth for a selected group of patients but of limited benefit as a therapy for improving mucosal disease and reducing clinical disease activity. Crohn's disease interacts with the GH-IGF-1 axis in important ways. Recent studies evaluating rhGH use in pediatric Crohn's disease have demonstrated some efficacy in reversing persistent linear growth delay but limited benefits in terms of improving mucosal disease and clinical disease activity. Larger studies of adequate power are needed to confirm a true benefit in terms of growth, to examine a potential benefit with regard to modification of disease activity, and to evaluate long-term risks.


Multipurpose microfluidic probe.
Microfluidic systems allow (bio)chemical processes to be miniaturized with the benefit of shorter time-to-result, parallelism, reduced sample consumption, laminar flow, and increased control and efficiency. However, such miniaturization inherently limits the size of the solid objects that can be processed and entails new challenges such as the interfacing of macroscopic samples with microscopic conduits. Here, we report a microfluidic probe (MFP) that overcomes these problems by combining the concepts of 'microfluidics' and of 'scanning probes'. Here, liquid boundaries formed by hydrodynamic forces underneath the MFP confine a flow of processing solution and replace the solid walls of closed microchannels. The MFP is therefore mobile and can be used to process large surfaces and objects by scanning across them. We illustrate the versatility of this concept with several examples including protein microarraying, complex gradient-formation, multiphase laminar-flow patterning, erasing, localized staining of cells and the contact-free detachment of a single cell. Many constraints imposed by the monolithic construction of microfluidic channels can now be circumvented using an MFP, opening up new avenues for microfluidic processing.


First human experience with angiopeptin-eluting stent: a quantitative coronary angiography and three-dimensional intravascular ultrasound study.
Angiopeptin has been shown to reduce in-stent restenosis in various animal models. Meanwhile, BiodivYsio DD phosphorylcholine (PC)-coated stent provides a platform for local delivery of antiproliferative agents to the coronary artery. We studied the feasibility, safety, and impact on tissue growth of angiopeptin-eluting BiodivYsio DD PC-coated stents in human native de novo coronary lesions. We enrolled 14 patients (16 lesions) who underwent intravascular ultrasound (IVUS)-guided angiopeptin-eluting stent implantation in native coronary arteries between 3.0 and 4.0 mm in diameter with lesion length<or=18 mm. We successfully implanted 13 stents loaded with 22 microg of angiopeptin and three stents with 126 microg of angiopeptin. No major adverse cardiac events or target vessel failure occurred at 1-year clinical follow-up. All patients underwent 6-month angiographic and volumetric IVUS follow-up. In-stent late loss was 0.46+/-0.32 mm in the low-dose group and 0.26+/-0.14 mm in the high-dose group. Binary restenosis rate was 0%. Follow-up percentage neointimal hyperplasia by IVUS was 18.4%+/-22.5% for the low-dose group and 10.2%+/-5.8% for the high-dose group, respectively. There were no edge effect and late stent malapposition. Angiopeptin-eluting BiodivYsio DD PC stent appears feasible and safe in treating native de novo coronary lesions with modest degree of neointimal hyperplasia.


Prevalence and correlates of driving under the influence of stimulants: Evidence from a national sample.
Several million Americans use illicit stimulants every month and national data suggest stimulant use is increasing. However, little evidence exists that examines the prevalence and correlates of driving under the influence of stimulants (DUIS). The present study aimed to provide new evidence on the prevalence of DUIS in the U.S. adult population. This study examined data from 170,944 adults 18 and older in the 2016-2019 National Survey on Drug Use and Health. Using Stata and R, we estimated the prevalence and key correlates of DUIS among adults in the United States. The overall prevalence of DUIS was 0.7% among adults in general and 28.3% among past-year stimulant users. Among the full adult sample, the prevalence of DUI cocaine was 0.5% and the prevalence of DUI methamphetamine was 0.3%. More than one in five (21.6%) adults with past year cocaine use reported DUI of cocaine, while nearly one half (47.2%) of adults with past year methamphetamine use reported DUI of methamphetamine. There is also a substantially higher likelihood of driving under the influence of stimulants among individuals reporting early onset of use and among those meeting criteria for cocaine/methamphetamine use disorders. Among adults who used cocaine/methamphetamine, those who reported driving under the influence of stimulants were more than 2 times more likely to experience a depressive episode or psychological distress. Findings suggest that prevention/treatment approaches focused on multiple substances as well as mental health needs may be most appropriate for addressing the challenge of DUIS.


Clinical features and recovery pattern of secondary hypokalaemic paralysis.
Information regarding frequency, details of neurological signs and recovery patterns of patients with secondary hypokalaemic paralysis (HP) is limited. This study aimed to analyse the frequency, aetiology, clinical features and recovery patterns of patients with secondary HP. The clinical and laboratory records of 18 consecutive patients with secondary HP aged ≥ 18 years admitted to our hospital between April 2011 and March 2022 were reviewed. Patients with inherited hypokalaemic periodic paralysis were excluded. Of the 18 patients, 16 had a common aetiology: chronic alcoholism, diarrhoea or an imbalanced diet. Initial symptoms, such as fatigue, were often atypical. Three patients had prominent asymmetric limb weakness and four had predominant upper limb weakness. On admission, the mean serum potassium and creatine kinase (CK) levels of the patients were 1.90 mmol/L and 4488 U/mL, respectively. Ten patients (56%) had decreased potassium levels after admission, despite potassium replacement treatment (rebound hypokalaemia). Twelve patients presented with increased CK levels even after 2-5 days (delayed hyperCKaemia). Low serum magnesium levels significantly correlated with rebound hypokalaemia. Secondary HP can be caused by a variety of conditions, but mainly occurs due to lifestyle conditions/disorders. Secondary HP often presents with atypical symptoms, and the initial symptoms can be non-specific. Rebound hypokalaemia and delayed hyperCKaemia are common in secondary HP, despite potassium replacement. As such, careful serial monitoring is needed for patients with secondary HP.


Stop! In the name of transforming growth factor-beta: keeping estrogen receptor-alpha-positive mammary epithelial cells from proliferating.
Recent genetic and cell biological studies illustrate the importance of active transforming growth factor-beta signaling in preventing the proliferation of estrogen receptor-positive cells in the normal mammary gland, and suggest how the loss of this inhibition may be important in early breast cancer progression.


ISPCAN Child Abuse Screening Tool for Children (ICAST-C): Translation and adaptation to Mexican Spanish, and psychometric properties tested in Mexico City adolescents.
Research using the IPSCAN Child Abuse Screening Tool for Children (ICAST-C), has provided ample evidence of the magnitude of violence against children. Knowledge about its psychometric characteristics and validity is limited. Hence, our objective was to translate and culturally adapt the ICAST-C in adolescents from Mexico City and determine its psychometric properties. To determine the psychometric properties of the instrument 723 adolescents between 11 and 18 years of age from 9 public secondary schools in Mexico City participated. The study was carried out in two phases: 1) translation and adaptation of the instrument (in 5 steps) and 2) pilot evaluation of the psychometric properties. Total and factor reliabilities were determined, Pearson correlation was used for temporal stability while construct validity was determined by Confirmatory Factor Analysis (CFA), and final adequacy of the items eliminated by the CFA. We developed the culturally relevant Mexican Spanish version of the ICAST-C. The CFA confirmed the six-factor structure hypothesis. To improve the original model we eliminated ten items, the final model showed good global fit indices (χ2(1310) = 2207.68, p < .01, χ2/df = 1.68; CFI =0.95; RMSEA = 0.02 [CI95% 0.02-0.03]; SRMR = 0.08). Total and factor reliabilities were adequate (Alpha = 0.79-0.92, r = 0.52-0.75), except for the non-violent discipline factor (Alpha = 0.59, r = 0.38). While these data suggest that this version of the ICAST-C is valid and reliable for adolescents in Mexico City public secondary schools, further research should evaluate the psychometric properties in a national sample.


Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis.
Symptoms of treatment-induced menopause negatively affect quality of life and adherence to endocrine therapy of breast cancer (BC) survivors. Nevertheless, the use of systemic hormone replacement therapy (HRT) to mitigate these symptoms may be associated with an increased risk of disease recurrence in these patients. This systematic review and meta-analysis aimed to assess the safety of systemic HRT on risk of disease recurrence in BC survivors. A systematic search of PubMed up to April 20, 2021 was conducted to identify randomized controlled trials (RCTs) that investigated the risk of disease recurrence with the use of HRT in BC survivors. A random-effect model was applied to calculate the risk of recurrence, reported as pooled hazard ratio (HR) with 95% confidence intervals (CI). A subgroup analysis was performed to estimate the risk of recurrence according to hormone receptor status. Four RCTs were included in the meta-analysis (n = 4050 patients). Overall, 2022 patients were randomized to receive HRT (estrogen/progestogen combination or tibolone) and 2023 to the control group with placebo or no HRT. HRT significantly increased the risk of BC recurrence compared to placebo (HR 1.46, 95% CI 1.12-1.91, p = 0.006). At the subgroup analysis, the risk of BC recurrence with the use of HRT was significantly increased in patients with hormone receptor-positive disease (HR 1.8, 95% CI 1.15-2.82, p = 0.010) but not in those with hormone receptor-negative tumors (HR 1.19, 95% CI 0.80-1.77, p = 0.390). Use of HRT was associated with a detrimental prognostic effect in BC survivors, particularly in those with hormone receptor-positive disease. Alternative interventions to mitigate menopause-related symptoms should be proposed.


Development of clinical trial protocols involving advanced radiation therapy techniques: the European Organisation for Research and Treatment of Cancer Radiation Oncology Group approach.
The European Organisation for Research and Treatment of Cancer (EORTC) Master Protocol for phase III radiation therapy (RT) studies was published in 1995 to define in a consistent sequence the parameters which must be addressed when designing a phase III trial 'from the rationale to the references'. This was originally implemented to assist study investigators and writing committees, and to increase homogeneity within Radiation Oncology Group (ROG) study protocols. However, RT planning, delivery, treatment verification and quality assurance (QA) have evolved significantly over the last 15 years and clinical trial protocols must reflect these developments. The goal of this update is to describe the incorporation of these developments into the EORTC-ROG protocol template. Implementation of QA procedures for advanced RT trials is also briefly described as these essential elements must also be clearly articulated. This guide may assist both investigators participating in current ROG trials and others involved in writing an advanced RT trial protocol.


Structural characterization of two isolectins from the marine red alga Solieria filiformis (Kützing) P.W. Gabrielson and their anticancer effect on MCF-7 breast cancer cells.
As described in the literature, Solieria filiformis lectin (SfL) from the marine red alga S. filiformis was found to have antinociceptive and anti-inflammatory effects. In this study, we characterized two SfL variants, SfL-1 and SfL-2, with molecular mass of 27,552Da and 27,985Da, respectively. The primary structures of SfL-1 and SfL-2 consist of four tandem-repeat protein domains with 67 amino acids each. SfL-1 and -2 showed high similarity to OAAH-family lectins. 3D structure prediction revealed that SfL-1 and -2 are composed of two β-barrel-like domains formed by five antiparallel β-strands, which are connected by a short peptide linker. Furthermore, the mixture of isoforms (SfLs) showed anticancer effect against MCF-7 cells. Specifically, SfLs inhibited 50% of viability in MCF-7 cells after treatment at 125μg.mL-1, while the inhibition of Human Dermal Fibroblasts (HDF) was 34% with the same treatment. Finally, 24h after treatment, 25% of MCF-7 cells were in early apoptosis and 35% in late apoptosis. Evaluation of pro- and anti-apoptotic gene expression of MCF-7 cells revealed that SfLs induced caspase-dependent apoptosis within 24h.


Clinical significance of mitochondrial glutamic-oxaloacetic transaminase in serum of patients with liver disease.
Serum mitochondrial glutamic-oxaloacetic transaminase activity was determined in 83 patients with various liver diseases and 10 healthy adults. 1) The average of mitochondrial glutamic-oxaloacetic transaminase value was 1.2 mU in healthy adults, 8.3 mU in patients with acute hepatitis, 13.7 mU in patients with post-transfusion hepatitis, 5.0 mU in patients with persistent hepatitis, 4.5 mU in patients with chronic inactive hepatitis, 9.6 mU in patients with chronic active hepatitis, 5.6 mU in liver cirrhosis, and 295 mU in a patient with fulminant hepatitis. 2) While one patient with acute hepatitis showed the highest value in the group of 29 mU, one patient with fulminant hepatitis showed an extremely high value of 295 mU, revealing an obvious difference between them. 3) One patient with fresh myocardial infarction also showed an extremely high value of 110 mU.


Quantifying (12/13)CH(4) migration and fate following sub-surface release to an agricultural soil.
Following gas generation in a Geological Disposal Facility (GDF), (14)C-containing gases could migrate through the geosphere, eventually diffusing into soils at the Earth's surface. This paper reports summary results from laboratory and field experiments to obtain information on the probable rates of a) diffusive transport and b) oxidation of (12/13)CH(4) (as a surrogate for (14)CH4) in a typical agricultural soil in the UK. Rates of CH(4) oxidation were generally low in the field and undisturbed soil columns, though a re-packed column of homogenised topsoil oxidised ambient atmospheric CH(4) 20× faster than an undisturbed soil column. In contrast to low observed rates of CH(4) oxidation, the effective diffusion of CH(4) through the soil was rapid. Isotopically labelled CH(4) injected at a depth of 45 cm in the field diffused to the surface and exited the soil over a time period ranging from 8 to 24 h. The rate of CH(4) diffusion through the soil was increased by the presence of ryegrass roots which increased soil porosity and decreased water content. δ(13)C values for laboratory column soils after labelled CH(4) injection experiments showed no sign of residual (13)C, despite the extremely high δ(13)C values of the injected (12/13)CH(4). If laboratory observations are confirmed by measurements in field samples it can be concluded that the majority of (14)CH(4) from a GDF which enters a soil with low methanotrophic activity will be lost to the free atmosphere after diffusing rapidly through the soil column.


Interstrand duplexes in Friend erythroleukemia nuclear RNA. The interaction of non-polyadenylated nuclear RNA with polyadenylated nuclear RNA and with small nuclear RNAs.
Intermolecular duplexes among large nuclear RNAs, and between small nuclear RNA and heterogeneous nuclear RNA, were studied after isolation by a procedure that yielded protein-free RNA without the use of phenol or high salt. The bulk of the pulse-labeled RNA had a sedimentation coefficient greater than 45 S. After heating in 50% (v/v) formamide, it sedimented between the 18 S and 28 S regions of the sucrose gradient. Proof of the existence of interstrand duplexes prior to deproteinization was obtained by the introduction of interstrand cross-links using 4'-aminomethyl-4,5',8-trimethylpsoralen and u.v. irradiation. Thermal denaturation did not reduce the sedimentation coefficient of pulse-labeled RNA obtained from nuclei treated with this reagent and u.v. irradiated. Interstrand duplexes were observed among the non-polyadenylated RNA species as well as between polyadenylated and non-polyadenylated RNAs. beta-Globin mRNA but not beta-globin pre-mRNA also contained interstrand duplex regions. In this study, we were able to identify two distinct classes of polyadenylated nuclear RNA, which were differentiated with respect to whether or not they were associated with other RNA molecules. The first class was composed of poly(A)+ molecules that were free of interactions with other RNAs. beta-Globin pre-mRNA belongs to this class. The second class included poly(A)+ molecules that contained interstrand duplexes. beta-Globin mRNA is involved in this kind of interaction. In addition, hybrids between small nuclear RNAs and heterogeneous nuclear RNA were isolated. These hybrids were formed with all the U-rich species, 4.5 S, 4.5 SI and a novel species designated W. Approximately equal numbers of hybrids were formed by species U1a, U1b, U2, U6 and W; however, species U4 and U5 were significantly under-represented. Most of these hybrids were found to be associated stably with non-polyadenylated RNA. These observations demonstrated for the first time that small nuclear RNA-heterogeneous nuclear RNA hybrids can be isolated without crosslinking, and that proteins are not necessary to stabilize the complexes. However, not all molecules of a given small nuclear RNA species are involved in the formation of these hybrids. The distribution of a given small nuclear RNA species between the free and bound state does not reflect the stability of the complex in vitro but rather the abundance of complementary sequences in the heterogeneous nuclear RNA.(ABSTRACT TRUNCATED AT 400 WORDS)


Retrospective study to identify predictors of the presence and rapid progression of aortic dilatation in patients with bicuspid aortic valves.
Aortic dilatation is common among adults with bicuspid aortic valves (BAV). Predictors of risk and progression of aortic dilatation are not well described in this setting. We analyzed retrospective data on the presence of dilation in several aortic segments in 156 adult patients with BAV who had serial echocardiograms performed at least 1 year apart. Various risk factors for the presence and progression of aortic dilatation were identified. Mean echocardiographic follow-up was 3.8 +/- 1.4 years, yielding a total of 582 patient-years. Independent predictors of having a dilated aorta at baseline were age (odds ratio [OR] 1.06, 95% CI 1.03-1.09), body surface area (OR 8.78, 95% CI 1.08-71.70) and moderate to severe aortic regurgitation (OR 6.38, 95% CI 2.51-16.20). During echocardiographic follow-up, 16 (15.2%) patients developed dilatation (incidence 4 cases per 100 patient-years). Mean annual rates of progression were estimated at 0.37 mm (95% CI 0.17-0.57), 0.18 mm (95% CI 0.05-0.31), 0.17 mm (95% CI 0.06-0.29) and 0.18 mm (95% CI 0.05-0.31) for the ascending aorta, sinotubular junction, aortic sinus and aortic annulus, respectively. Fusion of the right and left valve leaflets was associated with rapid aortic dilatation (OR 2.92, 95% CI 1.15- 7.41) whereas prior coarctation repair was associated with protection from rapid aortic dilatation (OR 0.13, 95% CI 0.04-0.40). Patients with BAV and increased age, high body surface area and moderate to severe aortic regurgitation are more likely to have a dilated aorta. Patients with right-to-left leaflet fusion are at increased risk of rapid aortic dilatation.


[Unsuccessful treatment with OK-432 picibanil for orbital lymphangioma].
Lymphangioma is a malformation of the lymphatic system. The classic approach is surgery. We report a case of orbital lymphangioma in a girl who was given OK-432 to avoid surgery and its complications. OK-432 is a lyophilized mixture of group A Streptococcus pyogenes which produces a fibrosis limited to the lesion with a high cure rate. The main advantages are the easy intra-lesional application. with no scars and or damage of closed areas. Its main disadvantage is a significant local inflammatory reaction.


Relationship of cell-mediated cytotoxicity against melanoma cells to prognosis in melanoma patients.
The cell-mediated cytotoxicity (CMC) of blood mononuclear cells against cultured human melanoma cells was measured in patients after surgical removal of localized melanoma, at a time when they were considered on clinical grounds to be free of melanoma. It was found that the distribution of CMC values against melanoma cells in melanoma patients was different from that in control subjects, and several sub-populations of melanoma patients were evident on the basis of these measurements. No difference in distribution of CMC values was found against non-melanoma cells, which suggested the changes were specific for melanoma. The proportion of patients with recurrence of melanoma was compared between the patient groups with low, normal or high CMC values against cultured melanoma cells after surgery. Analysis for periods extending to 2 years showed that patients with low CMC values after surgery had a significantly higher incidence of recurrence from melanoma than patients with normal or high CMC values. These results suggest there may be a sub-group of melanoma patients who have intrinsically low CMC against melanoma cells, and that this may be an important predisposing factor in the development of recurrent melanoma.


Analysis of domestic animal movements in Colombia (2006-2014) and their possible influence on the bovine brucellosis spread.
Bovine brucellosis is a zoonotic disease that causes great economic losses. The disease is endemic in Colombia and animal movements from infected herds carry a risk of introduction to other herds. With the objective of analyzing the animal movements and determining their relationship with bovine brucellosis, we performed a descriptive analysis of the space-time movement of livestock in Colombia between 2006 and 2014. Multiple linear regression models (MLR) were employed to determine the relationship between brucellosis status and animal movements at the province level. The prevalence of bovine brucellosis in cattle was the dependent variable, and a total of 14 independent variables related to location, year, census, and animal movements were included. The prevalence of bovine brucellosis was significantly affected by the province (F = 3.42; P < 0.001), the year (F = 9.03; P < 0.001), and bovine (F = 5.45; P = 0.02) and equine movements (F = 3.8; P = 0.053). Fewer cattle and more horses entered provinces with high prevalence than those with low prevalence, indicating the possible relationship between the animal movements and the brucellosis infection in the country.


Innate sensors for Gram-positive bacteria.
More than half of invasive bacterial infections are Gram-positive in origin. This class of bacteria has neither endotoxins nor an outer membrane, yet it generates some of the most powerful inflammatory responses known in medicine. Some recent seminal studies go a long way toward settling the controversies that surround the process by which Gram-positive bacterial surfaces trigger the human immune system. Although the components of the cell wall are now chemically defined in exquisite detail and the interaction with the toll-like receptor 2 pathway has been discovered, it is only very recently that definitive studies combining these advanced biochemical and cell biological tools have been carried out. It is these breakthrough studies that have finally confirmed the paradigm of innate sensors for Gram-positive bacteria.


Andrographolide ameliorates intracerebral hemorrhage induced secondary brain injury by inhibiting neuroinflammation induction.
Microglia activation and neuroinflammation play important roles in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). In this study, we attempted to investigate the potential effects of Andrographolide (Andro) on ICH-induced SBI and the possible mechanisms behind these effects. Andro treatment effectively reduced neuronal cell death and degeneration and alleviated neurobehavioral disorders and brain edema in vivo. In an in vitro study, microglia activation-induced neuronal cell death was ameliorated by Andro treatment. In addition, microglia activation and neuroinflammation were induced by ICH, exhibiting elevated cytokine levels, which could be reversed with Andro treatment. The levels of TNF-α and IL-6 were significantly decreased after treatment with Andro, both in vivo and in vitro, due to the inhibition of nuclear transcription factor-κB (NF-κB) signaling pathway activation. Meanwhile, Andro decreased the levels of IL-1β and LDH, as well as microglia pyroptosis induced by ICH by suppressing the assembly of the nucleotide-binding oligomerization domain like receptor protein 3 (NLRP3) inflammasome. In summary, this study reveals an anti-inflammatory effect of Andro and its potential mechanisms, and it shows that Andro is a potential candidate for improving ICH-induced SBI.


Bile salts and their importance for drug absorption.
Bile salts are present in the intestines of humans as well as the animals used during the development of pharmaceutical products. This review provides a short introduction into the physical chemical properties of bile salts, a description of the bile concentration and composition of bile in different animal species and an overview of the literature investigating the influence of bile salts on the in vivo performance of different compounds and drug formulations. Generally, there is a positive effect on bioavailability when bile is present in the gastro-intestinal tract, independent of the formulation systems, e.g. suspensions, solutions, cyclodextrin complexes or lipid based formulations, but a few exceptions have also been reported.


ELITA consensus statements on the use of DAAs in liver transplant candidates and recipients.
The advent of safe and highly effective direct-acting antiviral agents (DAAs) has had huge implications for the hepatitis C virus (HCV) transplant field, and changed our management of both patients on the waiting list and those with HCV graft re-infection after liver transplantation (LT). When treating HCV infection before LT, HCV re-infection of the graft can be prevented in nearly all patients. In addition, some candidates show a remarkable clinical improvement and may be delisted. Alternatively, HCV infection can be treated post-LT either soon after the transplant, taking advantage of the removal of the infected native liver, or at the time of disease recurrence, as was carried out in the past. In either case, some DAAs have a limited use because of their drug to drug interactions with various immunosuppressants as well as the many other drugs liver transplant recipients are often prescribed. In addition, some DAAs should be avoided in case of severe renal failure, which is not an unusual complication after LT. The present document provides a series of consensus statements on the LT issues that have not been extensively addressed previously. These statements have been developed to support physicians and other stakeholders in charge of LT candidates and recipients when deciding to treat HCV, especially in difficult situations.


Exploring the Appropriateness of Culturally Safe Dementia Information with Indigenous People in an Urban Northern Ontario Community.
Ce projet en application de connaissances a exploré la pertinence d'une documentation en promotion de la santé élaborée pour une population autochtone nationale en vue de son utilisation dans une communauté autochtone urbaine du nord de l'Ontario. Une approche décolonisée et communautaire de recherche-action participative faisant appel à l'épistémologie tribale a été suivie pour former un groupe consultatif autochtone local et établir un partenariat avec le N'Swakamok Native Friendship Centre. Deux groupes de discussion (n=8) composés d'adultes autochtones et cinq entrevues individuelles avec des aidants autochtones soignant une personne atteinte de démence ont alimenté l'analyse thématique qualitative. Quatre thèmes sont ressortis des données: (1) la nécessité d'une compréhension commune des cultures autochtones et occidentales dans le cadre des soins de santé; (2) l'amélioration de la communication interculturelle dans les discussions sur la santé; (3) l'ancrage du matériel de promotion de la santé dans la culture, et (4) les stratégies autochtones de littératie en matière de santé et la sensibilisation aux maladies neurodégénératives. Considérant que les prestataires de soins de santé cherchent des moyens efficaces pour communiquer avec les peuples autochtones, il est important de fournir de l'information pertinente localement et sur le plan culturel afin d'améliorer l'adoption et l'efficacité chez ces populations. This knowledge translation project explored the appropriateness of utilizing health promotion materials developed for a national Indigenous population with Indigenous people living in a northern Ontario urban community. A de-colonized, community-based participatory action research approach using tribal epistemology assisted in establishing a local Indigenous advisory group and a partnership with the N'Swakamok Native Friendship Centre. Two focus groups (n = 8) with Indigenous adults and five one-on-one interviews with Indigenous caregivers of a person with dementia informed a qualitative thematic analysis. Four themes emerged from the data: (1) the need for shared understandings of Indigenous and Western cultures in health care; (2) improving cross-cultural communication within health-related encounters; (3) grounding health promotion materials in culture; and (4) Indigenous health literacy strategies for dementia awareness. As health care providers search for effective ways to communicate with Indigenous people, it is important to deliver locally and culturally relevant information to improve uptake and effectiveness by Indigenous people. Maanda enkiichigaadeg binda kenjigemgad gezhi nakaasang dibaajimowinan gaazhitoong giiwedinong anishinaabek endaajig nji. Enanchgwenzigwaa miinwaa N'swakamok Friendship Center maamwi giinaadmaadok nokiitmowaad wii maandonaa'aad waa nkwenmaagenjig. Niish we'aangizijig, kchi aak miinwaa enkiitaagejig gii nibwaachidook nenendamaawziwin nji wii rnkamwaad ge minodaapinigaadeg. Niiwin giibi zikaamgadoon ge naadmaagemgak. (1) Zhindawendaagwod nsastaadwin wiiteg Anishinaabe miinwaa Ewaabshkiiwed ezhi naagdawendiwaad; (2) Weweni wii ginoonding nokiitaageng; (3) Wii kinoomaading weweni dibaajimowinan waazhi giniwendizad bemaadzid; miinwaa (4) Anishinaabe ji nsastang enaabiisjigeng nenendamaawziwin nji. Epiichtaawaad bemiikgagejig wii mkamowaad gezhi ginoonaawaad Anishinaaben, kchi piitendaagwad weweni ji nsastamookiiwaad mii dash dani naawsek.