The content expert program: A structured approach to increase emergency medicine resident scholarly activity.
The Accreditation Council for Graduate Medical Education requires residents to participate in scholarship and requires residency programs to provide an environment within which residents can acquire skills related to scholarly activities. However, consensus on the definition of scholarship and structure of program environments does not yet exist. We designed and implemented a content expert program (CEP) in 2015, in which each resident worked with a faculty advisor to develop a longitudinal scholarly activity linked to a core area of practice and, in doing so, became the department's "content expert." We hypothesized that the CEP would significantly increase the number of scholarly outputs per resident. The CEP was structured around an oversight committee composed of key faculty members, which guided development of CEP projects through regular meetings and formative feedback. Each resident generated one or more scholarly outputs from their content area. Outputs were categorized into educational, operational, research, and miscellaneous domains and further identified as intradepartmental, interdepartmental, or interdisciplinary collaborations. The number of outputs was compared to the baseline number of scholarly activities per resident at the study program using a Mann-Whitney U test. A total of 187 scholarly outputs were generated by 76 residents, which equated to 31.2 outputs per year, or 2.5 outputs per resident. This was a significant increase compared to the program baseline of one output per resident (p = 0.003). Eighteen distinct types of outputs spanned four major categories. Of the outputs, 37 were interdepartmental, 42 were interdisciplinary, and 32 were intradepartmental. The CEP proved to be a sustainable way to significantly increase scholarly activity and additionally improved collaborative efforts. With the appropriate structure and willing faculty in place, such a program can enhance the practical education provided by residency programs.


Hemin-decreased cadmium uptake in pak choi (Brassica chinensis L.) seedlings is heme oxygenase-1 dependent and relies on its by-products ferrous iron and carbon monoxide.
Cadmium (Cd) is a major pollutant in farmland, which not only greatly restricts crop production, but also brings a serious threat to human health through entering the food chain. Our previous study showed that hemin treatment could reduce the accumulation of Cd in pak choi seedlings. However, the underlying mechanism remains unclear. In this study, we used non-invasive micro-test technology (NMT) to detect the real-time Cd2+ flux from pak choi roots and demonstrated that hemin treatment decreased Cd uptake rather than its translocation within plants. Moreover, through comparing the responses of different chemical treatments in pak choi seedlings and Arabidopsis wild-type and heme oxygenase-1 (HO-1) mutant, we provided evidence that hemin-decreased Cd uptake was HO-1 dependent. Furthermore, analyses of hemin degradation products suggested that the hemin-derived suppression of Cd uptake suppression was probably relying on its degradation by-products, ferrous iron (Fe2+) and carbon monoxide (CO), via repressing the expression of a Fe2+/Cd2+ transporter BcIRT1 in pak choi roots.


Effects of Mediterranean diets on kidney function: a report from the PREDIMED trial.
Epidemiologic observations have linked healthy dietary patterns to improved kidney function. We assessed the effects of the Mediterranean diet (MedDiet) on kidney function in both a cross-sectional assessment and after a 1-year intervention in a cohort of the PREDIMED (Prevención con Dieta Mediterránea) Study, a multicenter 3-arm randomized clinical trial to determine the efficacy of the MedDiet on primary cardiovascular prevention. Community-dwelling men aged 55-80 years and women aged 60-80 years at high risk of cardiovascular disease from Reus, Spain. Participants were randomly assigned to 3 ad libitum diets: a MedDiet supplemented with virgin olive oil (MedDiet + olive oil), a MedDiet supplemented with mixed nuts (MedDiet + nuts), or a control low-fat diet. Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (ACR). Nutrient intake, adherence to the MedDiet, lifestyle variables, cardiovascular risk factors, serum urea and creatinine concentrations, eGFR, and urinary ACR were evaluated at baseline and after intervention for 1 year. Baseline kidney function markers were similar across quartiles of adherence to the MedDiet in 785 participants (55% women; mean age, 67 years). After a 1-year intervention in 665 participants, the 3 dietary approaches were associated with improved kidney function, with similar average increases in eGFR (4.7 [95% CI, 3.2-6.2], 3.5 [95% CI, 1.9-5.0], and 4.1 [95% CI, 2.8-5.5] mL/min/1.73 m(2) for the MedDiet + olive oil, MedDiet + nuts, and control groups, respectively [P < 0.001 vs baseline for each; P = 0.9 for differences among groups]), but no changes in ACRs after adjustment for various confounders. Generalization of results to other age groups or ethnicities. GFR was not directly measured. The results do not support the notion that the MedDiet has a beneficial effect on kidney function over and above that of advice for a low-fat diet in elderly individuals at high cardiovascular risk.


Qumquad: a UML-based approach for remodeling of legacy systems in health care.
Health care information systems still comprise legacy systems to a certain extent. For reengineering legacy systems a thorough remodeling is inalienable. Current modeling techniques like the Unified Modeling Language (UML) do not offer a systematic and comprehensive process-oriented method for remodeling activities. We developed a systematic method for remodeling legacy systems in health care called Qumquad. Qumquad consists of three major steps: (i) modeling the actual state of the application system, (ii) systematic identification of weak points in this model and (iii) development of a target concept for the reimplementation considering the identified weak points. We applied Qumquad for remodeling a documentation and therapy planning system for pediatric oncology (DOSPO). As a result of our remodeling activities we regained an abstract model of the system, an analysis of the current weak points of DOSPO and possible (partly alternative) solutions to overcome the weak points. Qumquad proved to be very helpful in the reengineering process of DOSPO since we now have at our disposal a comprehensive model for the reimplementation of DOSPO that current users of the system agree on. Qumquad can easily be applied to other reengineering projects in health care.


Synthesis of β-boswellic acid derivatives as cytotoxic and apoptotic agents.
A series of β-boswellic acid derivatives were synthesized and evaluated for anticancer activity. One of the lead analog 4f displayed significant anticancer activity against a panel of cancer cells as well as substantially inhibited colony formation in HCT-116 cells. Furthermore, 4f was found to be a potent inducer of apoptosis confirmed by loss of mitochondrial membrane potential, DAPI staining, Western blotting and ROS generation.


A comparison of a new slow release aspirin ("slow aspirin") with plain aspirin in the treatment of rheumatoid disease.
In a single centre double-blind crossover study in eighteen patients with established rheumatoid disease, a new slow release aspirin ("slow aspirin") was compared with plain aspirin with respect to patient tolerability and gastric mucosal damage as observed at gastroscopy. "Slow aspirin" was significantly better than plain aspirin with regard to gastroscopic findings. With "slow aspirin", the gastric mucosal appearances were definitely better in eight patients, worse in two, and eight showed no difference. There was a high incidence of gastric ulceration or erosions in the groups as a whole (39%) but few patients complained of dyspepsia. There was little difference in the ability of both plain and "slow aspirin" in controlling the patients' joint symptoms. Evidence has been provided to suggest that "slow aspirin" is less injurious to the gastric mucosa. In an attempt to reduce gastric mucosal damage due to prolonged aspirin treatment it is therefore concluded that "slow aspirin" merits consideration in the management of chronic rheumatoid disease.


Effects of gangliosides GM1 and GD1a on GAP-43 phosphorylation and dephosphorylation in isolated growth cones.
Phosphorylation of the nervous system-specific protein GAP-43 in growth cones in vivo increases as the growth cones near their targets, at a time when the gangliosides GM1 and GD1a are being accumulated in the growth cone membrane, thus raising the possibility that the gangliosides could modulate GAP-43 behavior. We used a subcellular fraction of intact isolated growth cones to show that both GM1 and GD1a affected the calcium-dependent posttranslational regulation of GAP-43 in several similar ways. Both gangliosides induced rapid incorporation of phosphate into GAP-43; however, the induction was undetectable with our antibody 2G12 that is specific for kinase C-phosphorylated GAP-43. Furthermore, neither ganglioside stimulated kinase C activity in isolated growth cones, suggesting that the rapid phosphorylation may not be on Ser41, the kinase C site. However, both gangliosides did induce a slower accumulation of GAP-43 phosphorylated on Ser41, apparently by inhibiting a phosphatase. Finally, calcium-dependent proteolysis of GAP-43 was also stimulated by both GM1 and GD1a. In contrast, GD1a, but not GM1, caused the redistribution of GAP-43 into the isolated growth cone cytoskeleton. The results demonstrate that both gangliosides can modulate the calcium-dependent regulation of GAP-43.


Acute Coronary Syndromes in Antiphospholipid Syndrome-above Suspicion: A Systematic Review.
Antiphospholipid syndrome(APS) is an autoimmune disorder characterized clinically by vascular thrombosis and/or pregnancy morbidity, associated with persistently elevated titers of antiphospholipid antibodies on at least two measurements over 12 weeks apart. In this study, we conducted a systematic review of the literature utilizing the Pubmed platform, in order to acquire clinical information about acute coronary syndromes in patients with APS. The obtained articles were reviewed in order to register the clinical characteristics, the rate of occurrence, the prognosis and the therapeutic approach of these patients. APS should be considered in young patients with acute myocardial infarction, even in patients with normal coronary arteries. The pharmaceutical approach is mainly based on the vitamin K antagonists, and in certain occasions aspirin, without any definite guidelines on the subject. Further randomized clinical trials are imperative for a better understanding of the particular characteristics of this group of patients, so that a more complete therapeutic approach to be obtained.


Saccharocin, a new aminoglycoside antibiotic. Fermentation, isolation, characterization and structural study.
A new aminoglycoside antibiotic, saccharocin has been isolated from the fermentation broth of Saccharopolyspora sp. AC-3440 (FERM P-6238) by column chromatography on a cation-exchange resin. Saccharocin is active against Gram-positive and Gram-negative bacteria. The structure was elucidated to be 4"-deamino-4"-hydroxyapramycin by 13C NMR spectral analysis.


Characterization of mutations in the reverse transcriptase region of hepatitis B virus in treated and untreated chronic hepatitis B patients.
The reverse transcriptase (RT) region of the hepatitis B virus (HBV) is the target of antiviral treatment. However, the discrepancy in RT mutations between nucleos(t)ide analogue (NA)-treated and -untreated chronic hepatitis B (CHB) patients is un clear. Serum samples were collected from 119 NA-treated and 135 NA-untreated patients. The sampling time was decided by the clinician. Full-length HBV RT regions were amplified using nest polymerase chain reaction. The mutations within the RT region were analysed by direct sequencing. The incidence of RT mutations in treated patients was higher than that in untreated patients (p<0.05). The classic drug-resistant mutations were detected in 44.5% (53/119) of treated patients, which was significantly higher than in untreated patients (6.7% [9/135]) (p<0.05). The non-classical mutations showed their complexity and diversity in both patient groups. Multiple mutations (three or more) were more frequent in treated patients than in untreated patients (p<0.05). Several novel mutations might be related to NA resistance. The selection pressures of NAs accelerated the development of RT mutations, especially within the functional domain. Mutations in the RT region occurred not only at classical sites, but also at other non-classical sites, which might be related to drug resistance and/or viral replication. The biological function and fitness of HBV isolates harbouring these novel mutations need further in vitro and in vivo verification experiments.


Thyroid function tests in the elderly in the community.
A study of the well elderly living at home has demonstrated that the ranges for serum thyroxine (T4), triiodothyronine (T3) uptake and free-thyroxine index (FTI) are much narrower than those for the sick elderly in-patient. The prevalence of thyroid disease appears similar in both types of elderly population.


A measles virus subgenomic RNA: structure and generation mechanism.
A plaque-derived line of measles virus induced the synthesis of 21S subgenomic RNA in addition to 50S genomic RNA. The nucleotide sequence of the former RNA was determined in comparison with that of the latter. The 21S subgenomic RNA was 2646 nucleotides long and had a copyback structure containing a 50S genomic 5'-end. At the site where copying turns back, there was a 15-nucleotide-long sequence resembling the "measles virus consensus sequence" which is present at the beginning of each gene on the measles virus genome and is presumed to serve as a signal for the initiation of transcription. Recognition of the specific sequence may have been involved in the aberrant replication and may represent an additional and novel copy choice mechanism leading to the generation of subgenomic RNAs.


Presence of cytomegalovirus in cerebrospinal fluid of patients with Guillain-Barre syndrome.
Because poliomyelitis has been almost completely eradicated, Guillain-Barre syndrome (GBS) now accounts for most cases of acute flaccid paralysis. Understanding of the role of cytomegalovirus (CMV) in the pathogenesis of GBS is still very limited. We identified 42 CMV-seropositive patients with GBS between 1998 and 2001. Cerebrospinal fluid (CSF) and serum samples obtained from these patients were tested by CMV-specific polymerase chain reaction, and the glycoprotein B (gB) segment of the detected CMV genome was analyzed. Virological findings were compared with clinical characteristics and CSF laboratory values. CMV DNA was detected in 13 (31%) of 42 CSF samples from patients with GBS but was not detected in 42 CSF samples from age-matched control subjects with acute encephalopathy. CSF samples obtained early after the onset of GBS were significantly more likely to be positive for CMV DNA (P=.048). gB1 was the most prevalent genotype detected in patients with GBS (88%), followed by gB3 (8%) and gB2 (4%). CMV DNA was detected frequently in CSF samples from CMV-seropositive patients with GBS, especially early during the course of the disease. The clinical significance of this finding has yet to be elucidated, but early administration of antiviral therapy might prove to be beneficial for selected patients with GBS.


Entanglement and decoherence of a micromechanical resonator via coupling to a Cooper-pair box.
We analyze the quantum dynamics of a micromechanical resonator capacitively coupled to a Cooper-pair box. With appropriate quantum state control of the Cooper box, the resonator can be driven into a superposition of spatially separated states. The Cooper box can also be used to probe the decay of the resonator superposition state due to environmental decoherence.


Phosphorylation of MCM3 protein by cyclin E/cyclin-dependent kinase 2 (Cdk2) regulates its function in cell cycle.
MCM2-7 proteins form a stable heterohexamer with DNA helicase activity functioning in the DNA replication of eukaryotic cells. The MCM2-7 complex is loaded onto chromatin in a cell cycle-dependent manner. The phosphorylation of MCM2-7 proteins contributes to the formation of the MCM2-7 complex. However, the regulation of specific MCM phosphorylation still needs to be elucidated. In this study, we demonstrate that MCM3 is a substrate of cyclin E/Cdk2 and can be phosphorylated by cyclin E/Cdk2 at Thr-722. We find that the MCM3 T722A mutant binds chromatin much less efficiently when compared with wild type MCM3, suggesting that this phosphorylation site is involved in MCM3 loading onto chromatin. Interestingly, overexpression of MCM3, but not MCM3 T722A mutant, inhibits the S phase entry, whereas it does not affect the exit from mitosis. Knockdown of MCM3 does not affect S phase entry and progression, indicating that a small fraction of MCM3 is sufficient for normal S phase completion. These results suggest that excess accumulation of MCM3 protein onto chromatin may inhibit DNA replication. Other studies indicate that excess of MCM3 up-regulates the phosphorylation of CHK1 Ser-345 and CDK2 Thr-14. These data reveal that the phosphorylation of MCM3 contributes to its function in controlling the S phase checkpoint of cell cycle in addition to the regulation of formation of the MCM2-7 complex.


Poly(ε-caprolactone)-block-poly(ethyl ethylene phosphate) micelles for brain-targeting drug delivery: in vitro and in vivo valuation.
The purpose of this work was to investigate the potential of poly(ε-caprolactone)-block-poly(ethyl ethylene phosphate) (PCL-PEEP) micelles for brain-targeting drug delivery. The coumarin-6-loaded PCL-PEEP micelles (CMs) were prepared and characterized. The cellular uptake of CMs was evaluated on in vitro model of brain-blood barrier (BBB), and the brain biodistribution of CMs in ICR mice was investigated. PCL-PEEP could self-assemble into 20 nm micelles in water with the critical micelle concentration (CMC) 0.51 μg/ml and high coumarin-6 encapsulation efficiency (92.5 ± 0.7%), and the micelles were stable in 10% FBS with less than 25% leakage of incorporated coumarin-6 during 24 h incubation at 37°C. The cellular uptake of CMs by BBB model was significantly higher and more efficient than coumarin-6 solution (CS) at 50 ng/ml. Compared with CS, 2.6-fold of coumarin-6 was found in the brains of CM-treated mice, and C(max) of CMs was 4.74% of injected dose/g brain. The qualitative investigation on the brain distribution of CMs indicated that CMs were prone to accumulate in hippocampus and striatum. These results suggest that PCL-PEEP micelles could be a promising brain-targeting drug delivery system with low toxicity.


Wet Your Whistles: Alcohol-Induced Flushing With Use of Topical Calcineurin Inhibitors.
Localized flushing after alcohol ingestion is a reported adverse effect of 2 topical calcineurin inhibitors, tacrolimus and pimecrolimus, which are approved to treat atopic dermatitis and used off label for other dermatologic conditions. We propose techniques for alleviating this phenomenon.


Qualitative evaluation of pharmaceuticals and metabolites in hospital effluent: Influence of sample preparation technique and outranking by environmental risk using the ELECTRE method.
The presence of pharmaceuticals and metabolites in effluents has become a serious environmental problem, so it is essential to be able to monitor these microcontaminants using qualitative approaches, as well as to assess the potential environmental risks that such compounds may present. Therefore, in this study, suspect screening analysis was performed of 2030 pharmaceuticals and metabolites in hospital effluent samples, applying different sample preparation techniques. Additionally, a pioneering association of (Q)SAR assessment of identified contaminants with the ELECTRE multi-criteria decision analysis technique made it possible to prioritize analytes according to their environmental risk, in order to enable their inclusion in environmental monitoring programs. The results showed that the most advantageous alternative sample preparation technique consisted of cleanup (100 mg of silica/alumina sorbent) + dispersive liquid-liquid microextraction (7.5 of aqueous matrix, 325 μL of chloroform (extracting solvent), and 500 μL of acetonitrile as dispersing solvent). This procedure resulted in the identification of 70 pharmaceuticals and metabolites in the composite sample tested. The suspect screening analysis found a total of 105 microcontaminants, 28 of them being "confirmed compounds" and 77 being "suspect compounds". Of the compounds identified, 87% were pharmaceuticals and 13% were metabolites. The compounds identified were subsequently evaluated using different open access software packages, considering eight endpoints: mobility, persistence, estrogen receptor binding, wastewater treatment plant total removal, biodegradability, PBT (persistent, bioaccumulation and toxic), mutagenicity, and carcinogenicity. The (Q)SAR prediction results were used as input data for the ELECTRE outranking method. Categorization of the identified compounds by ELECTRE resulted in the kernel (priority compounds) and a further 19 groups. ELECTRE sensitivity evaluation indicated that for all the cases, the kernel and the following two groups coincided. The categorization provided by the ELECTRE method constitutes a highly intuitive decision and choice tool, which can assist in the selection of compounds if subsequent quantitative analysis is to be carried out.


The Lived Experience of Frailty in Patients Aged 60 Years and Older with Heart Failure: A Qualitative Study.
The prevalence of frailty among patients with heart failure is about 45%. Frailty may result in patients' functional decline, falls, disability, and decreased quality of life. Qualitative studies can explore older patients' perceptions of frailty and help patients cope with it. However, a qualitative approach that explores the experience of frailty in older patients living with heart failure is lacking. This study aimed to explore the lived experience of frailty in older patients with heart failure. This qualitative study applies Giorgi's phenomenological method. Data were collected from October 2019 to August 2020. Thirteen older patients with heart failure aged at least 60 years were recruited using purposive sampling from a medical center in Taiwan. The participants participated in an in-depth interview using a semistructured interview guide. Seven themes were identified: "being reborn at the end of the road but having difficulty recovering", "living with a disease with an ineffable feeling", "feeling like being drained: physical weakness and a dysfunctional body", "struggling with impaired physical mobility and facing unexpected events", "suffering from mental exhaustion", "receiving care from loved ones", and "turning over a new leaf". Frailty in older patients with heart failure was obscure and difficult to describe. Frailty could be improved by medical intervention, self-management, and social support but was difficult to reverse. Patients with heart failure should be evaluated for frailty using multidimensional assessment tools at first diagnosis and provided frailty-related information so that patients have proper insight into their disease as early as possible.


Ruxolitinib Benefits Some with Pancreatic Cancer.
A phase II trial found that the drug ruxolitinib extends the lives of some patients with metastatic pancreatic cancer who no longer responded to first-line therapy. Ruxolitinib, approved for treating myelofibrosis, blocks the JAK/STAT pathway, which promotes inflammation. Ruxolitinib increased median survival from 1.8 to 2.7 months in patients with pancreatic cancer who had high levels of the inflammation marker C-reactive protein in their blood.


Synchronized sipping in alcoholics and social drinkers; a preliminary investigation.
In a laboratory setting, social drinking couples synchronized a greater proportion of their sips of alcoholic beverages than did alcoholic husbands and their wives.


Digital image quantification of siderophores on agar plates.
This article presents visual image data and detailed methodology for the use of a new method for quantifying the exudation of siderophores during fungal growth. The data include images showing time series for calibration, fungal exudation, and negative controls, as well as replication accuracy information. In addition, we provide detailed protocols for making CAS assay layer plates, the digital analysis protocol for determining area of color change, and discuss growth media that do and do not work with the layer plate method. The results of these data, their interpretation, and further discussion can be found in Andrews et al., 2016 [1].


Experimental investigation of the optimal driving pressure for a larger-volume controllable jet injection system.
Jet injection technology has become the alternative drug delivery method of conventional needle-based injection due to its obvious advantages. In order to meet the demand for larger volume injection, the pneumatic jet injection systems have efficiently administrated vaccine up to 1 mL in human. Our recent study has also demonstrated that controlling the driving pressure enabled the pneumatic jet injection system to deliver larger volumes of drugs to target sites at desired rates and times. This work continues to explore the optimal two-phase driving pressure combination with better injection efficiency for typical larger-volume (1.0 mL) jet injection with controllable pneumatic jet injection system. Under the combination of a first phase driving pressure of 1.00 MPa and a second phase driving pressure ranging from 0.25 to 0.90 MPa, dynamic characteristics, dispersion characteristics and pharmacokinetic characteristics of this controllable jet injection system were quantitatively analyzed. In all experiments, it was confirmed that the optimal driving pressure combination of 1.0 mL ejection volume was close to (1.00-0.50) MPa. That is, the injection velocities of 151.85 m/s and 102.01 m/s for the first and second phase respectively facilitated better injection performance with a controlled release of 1.0 mL ejection volume. This strategy is practical for facilitating the clinical application of large-volume controllable jet injection systems.


Gemcitabine plus dose-escalated epirubicin in advanced breast cancer: results of a phase I study.
Gemcitabine has shown single-agent activity in metastatic breast cancer. Epirubicin is also widely used for the adjuvant and treatment of metastatic breast cancer. The toxicity profiles and modes of action are different which provides a good rationale for studying both drugs in combination. In a phase I study gemcitabine at a fixed dose of 1000 mg/m2 on days 1, 8, 15 of a 28 day cycle was combined with escalated weekly doses of epirubicin starting with an initial dose of 10 mg/m2. Patients had stage IV metastatic disease without previous chemotherapy except as adjuvant treatment. Nineteen patients were included in the study which defined the maximum tolerated dose (MTD) of epirubicin at 20 mg/m2. Myelosuppression was the dose limiting toxicity with leucopenia WHO grade 3 and 4 in 40.0% and 20.0%, neutropenia WHO grade 3 and 4 without neutropenic fever in 20.0% and 40.0% and thrombocytopenia WHO grade 4 in 20.0%. At the epirubicin 15 mg/m2 dose level, leucopenia (11.1% WHO grade 3) and neutropenia (12.5 and 37.5% WHO grade 3 and 4) were reported. Symptomatic toxicity was generally mild: nausea/vomiting in about 20% of patients (WHO grade 3 or 4) on both 15 and 20 mg/m2 epirubicin dose levels. Alopecia WHO grade 3 and 4 was seen in 2 patients at MTD. Four of 19 evaluable patients had a partial response. We conclude that the combination of gemcitabine and epirubicin is well tolerated and has promising activity. A phase II study is underway with gemcitabine 1000 mg/m2 and epirubicin 15 mg/m2 on days 1, 8 and 15 of a 28 day cycle.


The anatomical logic of smell.
Olfactory receptor neurons (ORNs) expressing the same odorant receptor gene share ligand-receptor affinity profiles and converge onto common glomerular targets in the brain. The activation patterns of different ORN populations, evoked by differential binding of odorant molecular moieties, constitute the primary odor representation. However, odorants possess properties other than receptor-binding sites that can contribute to odorant discrimination. Among terrestrial vertebrates, odorant sorptiveness--volatility and water solubility--imposes physicochemical constraints on migration through the nose during inspiration. The non-uniform distributions of ORN populations along the inspiratory axis enable sorptiveness to modify odor representations by affecting the number of molecules reaching different receptors during a sniff. Animals can then modify and analyze odor representation further by the dynamic regulation of sniffing.


Parents sharing information with their children about genetic conditions.
Nurses are in an ideal situation to help families share information with their children about genetic conditions. While many factors contribute to this decision making, little is known about how parents decide when and how to convey this information to their children. The purpose of this qualitative analysis was to examine parents' beliefs and strategies related to sharing information about a genetic condition with their affected and unaffected children. One hundred thirty-nine parents participated in this study. Narrative analysis and fundamental qualitative description were employed to identify approaches and strategies that parents used to share information with their children. Parents' information sharing approaches and strategies were grounded in the goal of promoting the child's adaptation to the genetic condition. Parents shared information based on their assessment of the child's developmental readiness and interest and described information sharing as an unfolding process that continued throughout childhood. The approaches and strategies contribute to understanding the processes associated with information sharing between parents and their children and between health care professionals and parents.


Venous insufficiency in a young man secondary to a traumatic arteriovenous fistula.
The medical history in a young man who developed varicose veins and venous insufficiency secondary to an acquired arteriovenous fistula in the thigh is presented. The radiological and clinical findings are discussed. The disease process in the development of varicose veins is not fully understood and cannot be satisfactorily explained as a consequence of arterial pressure within the venous system or a defect in the venous valves alone. The widespread ectatic changes seen within the venous system in our patient suggests the activation of an unknown, possibly humoral factor, resulting in morphological modifications in the vein wall.


Efficacy and safety of ketotifen in young children with asthma.
Thirty children (aged 1 to 3 years) with mild to moderate asthma were entered into a 28-week double-blind, crossover study comparing the prophylactic effect of ketotifen and placebo. A patient daily diary card was used to document symptoms and concomitant medications taken during a 2-week baseline and subsequent 12-week drug/placebo period. This was followed by a 2-week washout and 12 more weeks of drug/placebo in a crossover design. Physician assessment was performed at the beginning, at the end of each period, and at 4-week intervals throughout the drug study. No significant difference was observed between ketotifen treatment and placebo treatment in any of the study parameters that were tested. A decrease in concomitant medication usage during the first treatment period with ketotifen was observed. The principle side effect of ketotifen therapy observed in this age group was weight gain. In contrast to studies in adults, no sedation was noted.


Mitochondrial reactive oxygen species production by fish muscle mitochondria: Potential role in acute heat-induced oxidative stress.
Acute heat challenge is known to induce cell-level oxidative stress in fishes. Mitochondria are well known for the capacity to make reactive oxygen species (ROS) and as such are often implicated as a source of the oxidants associated with this thermally-induced oxidative stress. This implication is often asserted, despite little direct data for mitochondrial ROS metabolism in fishes. Here we characterize mitochondrial ROS metabolism in three Actinopterygian fish species at two levels, the capacity for superoxide/H2O2 production and the antioxidant thiol-reductase enzyme activities. We find that red muscle mitochondria from all three species have measurable ROS production and respond to different assay conditions consistent with what might be anticipated; assuming similar relative contributions from difference ROS producing sites as found in rat skeletal muscle mitochondria. Although there are species and assay specific exceptions, fish mitochondria may have a greater capacity to produce ROS than that found in the rat when either normalized to respiratory capacity or determined at a common assay temperature. The interspecific differences in ROS production are not correlated with thiol-based antioxidant reductase activities. Moreover, mimicking an acute in vivo heat stress by comparing the impact of increasing assay temperature on these processes in vitro, we find evidence supporting a preferential activation of mitochondrial H2O2 production relative to the increase in the capacity of reductase enzymes to supply electrons to the mitochondrial matrix peroxidases. This supports the contention that mitochondria may be, at least in part, responsible for the ROS that lead to oxidative stress in fish tissues exposed to acute heat challenge.


Cloning, annotation and expression analysis of mycoparasitism-related genes in Trichoderma harzianum 88.
Trichoderma harzianum 88, a filamentous soil fungus, is an effective biocontrol agent against several plant pathogens. High-throughput sequencing was used here to study the mycoparasitism mechanisms of T. harzianum 88. Plate confrontation tests of T. harzianum 88 against plant pathogens were conducted, and a cDNA library was constructed from T. harzianum 88 mycelia in the presence of plant pathogen cell walls. Randomly selected transcripts from the cDNA library were compared with eukaryotic plant and fungal genomes. Of the 1,386 transcripts sequenced, the most abundant Gene Ontology (GO) classification group was "physiological process". Differential expression of 19 genes was confirmed by real-time RT-PCR at different mycoparasitism stages against plant pathogens. Gene expression analysis revealed the transcription of various genes involved in mycoparasitism of T. harzianum 88. Our study provides helpful insights into the mechanisms of T. harzianum 88-plant pathogen interactions.


Negative frequency dependent selection on plasmid carriage and low fitness costs maintain extended spectrum β-lactamases in Escherichia coli.
Plasmids may maintain antibiotic resistance genes in bacterial populations through conjugation, in the absence of direct selection pressure. However, the costs and benefits of conjugation for plasmid and bacterial fitness are not well understood. Using invasion and competition experiments with plasmid mutants we explicitly tested how conjugation contributes to the maintenance of a plasmid bearing a single extended-spectrum ß-lactamase (ESBL) gene (blaCTX-M-14). Surprisingly, conjugation had little impact on overall frequencies, although it imposed a substantial fitness cost. Instead, stability resulted from the plasmid conferring fitness benefits when rare. Frequency dependent fitness did not require a functional blaCTX-M-14 gene, and was independent of culture media. Fitness benefits when rare are associated with the core plasmid backbone but are able to drive up frequencies of antibiotic resistance because fitness burden of the blaCTX-M-14 gene is very low. Negative frequency dependent fitness can contribute to maintaining a stable frequency of resistance genes in the absence of selection pressure from antimicrobials. In addition, persistent, low cost resistance has broad implications for antimicrobial stewardship.


Controlled root targeted delivery of fertilizer using an ionically crosslinked carboxymethyl cellulose hydrogel matrix.
The recent increases in food prices caused by the corresponding increases in fertilizer costs have highlighted the demand for reducing the overuse of fertilizers in industrial agriculture. There has been increasing interest in developing plant root-targeted delivery (RTD) of fertilizers in order to address the problem of inefficient fertilizer use. The aim of this study is to develop a low cost controlled release device to deliver fertilizers to plant roots and thereby increase fertilizer use efficiency. The Root Targeted Delivery Vehicle (RTDV) is formed by dissolving Carboxymethyl Cellulose (CMC) chains in water, mixing it with liquid fertilizer and crosslinking using iron and calcium salts. Basic measurements quantifying nutrient release and green house growth trials were carried out to evaluate fertilizer use efficiency on wheat growing in nutrient depleted soil media. Growing wheat in nutrient depleted media showed that the RTDV permits a 78% reduction in the amount of fertilizer needed to achieve similar levels of plant yield in these conditions. Quantifying the losses associated with the RTDV synthesis showed that optimizing manufacturing could possibly increase this value as high as 94%. Furthermore, the delivery device showed a similar lifetime in soil to the plant's growth cycle, delivering fertilizer over the course of the plant's growth before removal from soil by degradation. These results illustrate the importance of fertilizer delivery in facilitating absorption and may have potential to vastly increase the use efficiency of fertilizers in soil, resulting in a significant reduction of costs and environmental damage. With more in depth study to quantify the fertilizer release and refine the device, there is great potential for the use of the RTDV as an effective means to increase fertilizer use efficiency in agriculture.


Cetuximab pharmacokinetic/pharmacodynamics relationships in advanced head and neck carcinoma patients.
Cetuximab associated with cisplatin and 5-fluorouracil is used to treat patients with inoperable or metastatic head and neck squamous cell carcinomas (HNSCC) up until disease progression or unacceptable toxicities. To date, no biomarkers of efficacy are available to select patients who will benefit from treatment. An ancillary pharmacokinetics (PK) exploration was performed in the context of a prospective study investigating circulating-tumour cells vs progression-free survival (PFS). Cetuximab plasma concentrations were analysed according to a population PK model. Individual exposure parameters were confronted with soluble epidermal growth factor receptor (sEGFR) concentrations, tumour response and PFS. PK data (28 patients, 203 observations) were best described by a two-compartment model with linear elimination. Performance status (PS) significantly correlated to both cetuximab clearance and central volume of distribution with both parameters increasing by 33.3% (95% CI 1-65.6) for each 1-point increase of PS compared to PS = 0. Univariate analysis showed that patients with higher trough cetuximab concentrations at Day 7 (Cmin,D7 ) had better tumour response (P = 0.03) and longer PFS (P = 0.035). However, multivariate analysis revealed that only PS and tumour size at baseline remained significantly associated with PFS. Levels of sEGFR increased during cetuximab treatment but were not associated with PFS in the multivariate analysis. Our study prospectively indicates that PS is likely a confounding factor in the relationship between cetuximab PK and PFS, patients with a poor PS having lower cetuximab plasma exposure and lower PFS.


Taenia solium metacestode antigens which are protective for pigs induce Th1/Th2 mixed responses in mice.
The purpose of this study was to determine the Th1 and Th2 cytokine responses induced by Taenia solium metacestode antigens in mice and correlate them with the immune responses elicited in vivo. To assess this aim, mice were inoculated with metacestode antigens. RNA was obtained from spleen cells of immunized or control mice incubated with metacestode antigens and used to determine the cytokine profile. Peripheral blood eosinophilia was measured daily in each mouse and specific serum antibody levels were determined. Results showed that metacestode antigens induce the synthesis of IL-4, IL-5 and IFN-gamma mRNAs in spleen cells. They also induced peripheral blood eosinophilia and elicited specific IgE and IgG antibodies, especially IgG1. Three antigens were recognized by all IgG subclasses and by IgE (104, 88 and 7 kDa), and a 57-kDa protein was recognized by IgG1, IgG2a, IgG2b, and IgE. IgG1 and IgG2b recognized 52, 30 and 20 kDa antigens. Immune responses elicited in vivo and the cytokine profile showed good correlation.


Safety and effectiveness of empagliflozin according to body mass index in Japanese patients with type 2 diabetes: a subgroup analysis of a 3-year post-marketing surveillance study.
Empagliflozin, a glucose-lowering drug licensed for type 2 diabetes (T2D), demonstrated tolerability and effectiveness overall in a post-marketing surveillance (PMS) study in Japan. However, the impact of body mass index (BMI) is unclear. This was a prespecified sub-analysis of the prospective, 3-year, PMS study of empagliflozin in Japan where the primary endpoint was adverse drug reactions (ADRs). We evaluated results according to BMI. We enrolled 7931 T2D patients treated with empagliflozin. Baseline mean age was 58.7 years; 63.01% were male. Baseline BMI was <20 kg/m2 in 2.06% of patients, while 21.28%, 37.35%, and 24.97% had BMI 20-<25, 25-<30 and ≥30 kg/m2, respectively. ADRs occurred in 19 (11.66%), 203 (12.03%), 411 (13.88%), and 295 (14.90%) patients with BMI <20, 20-<25, 25-<30 and ≥30 kg/m2, respectively. Excessive/frequent urination was the most frequent ADR of special interest in all BMI subgroups except 20-<25 kg/m2 (urinary tract infection). Mean change in glycated hemoglobin from baseline was -0.75%, with similar magnitude across BMI subgroups. Body-weight reduction seemed dependent on BMI, with almost no change in the <20 kg/m2 subgroup. Empagliflozin appeared well tolerated and effective in Japanese T2D patients regardless of BMI, although the number of patients with BMI <20 kg/m2 was small in this study.


Feasibility study of collagen membranes derived from bovine pericardium and intestinal serosa for the repair of cranial defects in ovariectomised rats.
The indication of biomaterials has increased substantially in the regenerative therapy of bone defects. However, in addition to evaluating the physicochemical properties of biomaterials, the quality of the recipient tissue is also essential for the osseointegration of implants, as abnormalities in bone metabolism, such as gonadal hormone deficiency, can influence bone healing. This study evaluated the osteoregenerative capacity of collagen membranes derived from bovine pericardium and intestinal serosa in the repair of cranial defects in ovariectomised rats. Thirty female Wistar rats were submitted to surgical creation of a 5-mm cranial bone defect. The rats were divided into a control group (not ovariectomised) and an ovariectomised group. The non-ovariectomised group was divided into three subgroups: control (G1) in which the defect was not filled with the biomaterial, and two subgroups (G2 and G3) that received the bovine pericardium- and serosa-derived collagen membranes, respectively. The ovariectomised group was divided into the same subgroups (G4, G5, and G6). The animals were sacrificed 8 weeks after surgery. The calvaria were removed for macroscopic and radiographic photodocumentation and processed for histomorphometric analysis of bone healing at the surgical site. Macroscopic, radiological, and microscopic analyses demonstrated the biocompatibility of the implanted collagen membranes, as indicated by the absence of infiltration and signs of inflammation at the surgical site. Histologically, discrete immature bone neoformation projecting from the margins of the defect was observed at the surgical site in ovariectomised groups when compared to the non-ovariectomised groups. The volume of newly formed bone was significantly higher in the non-ovariectomised groups (G1: 7.83%±1.32; G2: 21.33%±1.96; and G3: 22.83%±0.98) compared to the respective ovariectomised subgroups (G4: 3.16%±0.75; G5: 16.83%±0.98; and G6: 16.16%±0.75), thus demonstrating the deleterious effects of ovariectomy on bone homeostasis. Higher volumes of newly formed bone were observed in the groups receiving the membrane grafts (G2, G3, G5, and G6) compared to the control groups (G1 and G4). In conclusion, the bilateral ovariectomy compromises the ability to repair bone lesions grafted with osteoconductive biomaterials as in the case of collagen membranes derived from both bovine pericardium and intestinal serosa.


Secretin secretion in patients with duodenal ulcer, chronic pancreatitis and diabetes mellitus.
Secretin releasing response to intraduodenal acid infusion was investigated in 15 cases of diseased control, 7 cases of duodenal ulcer, 5 cases of chronic pancreatitis, and 6 cases of diabetes mellitus. Plasma secretin levels in response to duodenal acidification were less in duodenal ulcer and the appearance of the maximal peak was delayed compared with that found in control. It is suggested that the secretin release was impaired in duodenal ulcer in spite of hypersecretion of gastric acids. In chronic pancreatitis, secretin releasing response to acidification was markedly impaired, in addition, inhibition of secretin release by bicarbonate was diminished due to a lack of bicarbonate flow from the pancreas. On the other hand, although the response of secretin release in diabetes mellitus was also lower compared with that in control group, the capacity of secretin response showed values in-between control subjects and chronic pancreatitis. This research was supported in part by grant from the Ministry of Education, Science and Culture in Japan.


Severe thrombocytopenia after hepatitis B vaccine in an infant from Turkey.
Recombinant hepatitis B vaccine has been used widely in the world since 1991. The side effects of hepatitis B vaccine are seen rarely. In this paper, we present clinical and laboratory progress of an infant who gets severe thrombocytopenia after the second dosage hepatitis B vaccine. Our case is different from other cases because our patient is very young, the number of platelet is the lowest in the literature, and intravenous immunoglobulin (IVIG) are immunoglobulin (IVIG) are used in the treatment. Although it is a severe thrombocytopenia, the patient has recovered without any bleeding.


Mapping epistatic quantitative trait loci underlying endosperm traits using all markers on the entire genome in a random hybridization design.
Triploid endosperm is of great economic importance owing to its nutritious quality. Mapping endosperm trait loci (ETL) can provide an efficient way to genetically improve grain quality. However, most triploid ETL mapping methods do not produce unbiased estimates of the two dominant effects of ETL. A random hybridization design is an alternative method that may be used to overcome this problem. However, epistasis has an important role in the dissection of genetic architecture for complex traits. In this study, therefore, an attempt was made to map epistatic ETL (eETL) under a triploid genetic model of endosperm traits in a random hybridization design. The endosperm trait means of random hybrid lines, together with known marker genotype information from their corresponding parental F(2) plants, were used to estimate, efficiently and without bias, the positions and all of the effects of eETL using a penalized maximum likelihood method. The method proposed in this article was verified by a series of Monte Carlo simulation experiments. Results from the simulated studies show that the proposed method provides accurate estimates of eETL parameters with a low false-positive rate and a relatively short running time. This new method enables us to map triploid eETL in the same way as diploid quantitative traits.


Community-based intervention improves abortion knowledge and reduces abortion stigma among women in Oromia, Ethiopia: a quasi-experimental mixed methods evaluation.
Since liberalization of the Ethiopian abortion law, there have been significant improvements in the availability and utilization of facility-based abortion services in the country. However, nearly half of abortions still take place outside of health facilities, where the quality of procedures remains unknown. Abortion stigma is one reason that unsafe abortion persists. This study aims to evaluate the effect of community interventions conducted from 2016 to 2019 on the level and manifestation of abortion stigma and knowledge in a community in Oromia region, Ethiopia. The study is a quasi-experimental mixed methods evaluation including intervention and comparison communities. Two cross-sectional structured household surveys with independent samples, participatory evaluation wheels, and participatory impact diagrams were conducted with women of reproductive age (15-49) living in the communities. The baseline was conducted in 2016 and the endline in 2019. Difference-in-differences analysis was used to estimate the effect of the intervention on abortion knowledge and Stigmatizing Attitudes, Beliefs, and Actions Scale (SABAS) scores in the intervention community. One thousand five hundred fifty-five women participated in the household survey and 28 women participated in participatory evaluation meetings. Over one-third (37%) of women surveyed in the intervention community were exposed to the intervention activities. Knowledge of one or more indications of legal abortion increased from 21 to 85% in the intervention community, compared to an increase from 30 to 57% in the comparison. Mean SABAS scores decreased by 9.3 points in the intervention community and increased by 5.3 points in the comparison community. Differences-in-differences models indicate that exposure to the intervention resulted in decreased stigma scores (coefficient = - 9.33, p < 0.001) and increased knowledge (coefficient = 0.26, p < 0.001). This is one of the first studies to measure changes in community-level abortion stigma and knowledge over time in Ethiopia using a mixed method, quasi-experimental design. The results indicate that the community-based intervention improved abortion knowledge and reduced abortion stigma.


Overcoming the challenge of venous occlusion for lead implantation.
Vein stenosis or occlusion is a frequent finding in patients with previously-implanted transvenous leads. This editorial describes the different techniques that may be used to overcome this hurdle in case a new lead needs to be implanted, and discusses two case reports in this issue of the journal.


Psychometric properties of the CAST and SDS scales in young adult cannabis users.
To assess the validity of two cannabis use severity scales among young cannabis users and to evaluate their ability to detect Substance Use Disorders (SUD). 241 volunteers (18-25 years), with a wide spectrum of cannabis use in the last 12 months. The Cannabis Abuse Screening Test (CAST) and Severity of Dependence Scale (SDS) were self-administered. The Psychiatric Interview for Substance and Mental Disorders (PRISM) was used as gold standard for cannabis use disorders according to DSM-IV. Reliability and validity were assessed for two different CAST coding algorithms (b-binary and f-full) and for the SDS. In addition, the cannabis use diagnostic criteria contained in the PRISM were grouped to approximate forthcoming proposed DSM-V criteria to further evaluate these scales. 26.6% (95% CI: 21.0-32.2) of the subjects met criteria for cannabis dependence, and 49.0% (95% CI: 42.7-55.3) for cannabis use disorders. For both scales internal consistency (Cronbach's alpha>0.71) and test-retest intraclass correlation coefficients (>0.80) were good. The score 12 in the CAST-full discriminated better than others between presence and absence of dependence (27.0%; 95% CI: 21.4-32.6) while the score for discrimination of SUD was 9 (51.5%; 95% CI: 45.1-57.8). For the SDS the values were 7 (22.0%; 95% CI: 16.8-27.2) and 3 (64.7%; 95% CI: 58.7-70.8), respectively. According to proposed DSM-V criteria, for moderate and severe addiction the values for the CAST-f were 7 (68.5%; 95% CI: 62.5-74.3) and 12 (27%; 95% CI: 21.3-32.6) and for the SDS, 3 (65.0%; 95% CI: 58.7-70.8) and 7 (22%; 95% CI: 17.0-34.3), respectively. The CAST and SDS applied to young cannabis users are reliable and valid measures to detect cannabis use disorders when compared to both DSM-IV and proposed DSM-V criteria.


CsSAP, a teleost serum amyloid P component, interacts with bacteria, promotes phagocytosis, and enhances host resistance against bacterial and viral infection.
Serum amyloid P component (SAP) is a member of the pentraxins family that plays important roles in innate immunity in vertebrates. In fish, the biological function of SAP is essentially unknown. In this study, we examined the expression and function of a SAP homologue (CsSAP) from tongue sole Cynoglossus semilaevis. CsSAP shares 46%-58% overall sequence identities with known fish SAP and was upregulated in expression by bacterial and viral infection. Recombinant CsSAP (rCsSAP) exhibited differential binding capacities to a wide range of Gram-positive and Gram-negative bacteria and promoted uptake of the bound bacteria by host phagocytes. When introduced in vivo, rCsSAP enhanced host resistance not only to bacterial infection but also to viral infection. Consistently, antibody blockage of CsSAP significantly weakened the ability of tongue sole to clear invading bacteria. These results provide the first evidence that fish SAP contributes significantly to both antibacterial and antiviral immunities.


[The assignment of wines to location by determination of trace element patterns (author's transl)].
The concentrations of trace elements were determined in 70 wines by activation analysis and investigated as a function of location, grape variety and vintage year. It is possible using numerical taxonomy to cluster all the wines of one region by their greater similarity in trace element patterns. It is too early for a definative evaluation of the limits of this method.


Evaluating the effects of automated monitoring on driver non-compliance at active railway level crossings.
Collisions between road users and trains at urban railway level crossings persist, despite active protection. The number of railway level crossings in most settings render their removal unfeasible. To effectively reduce or manage risk, alternative treatments are required. Increases in road and rail traffic invariably result in congestion issues at urban railway level crossings, which influences non-compliances by road users. Automated enforcement is one form of treatment that is being considered to reduce such non-compliances. This study conceptualised and adopted a before-after design to evaluate the effect of a conspicuous monitoring system on non-compliances by vehicular road users at an active level crossing. Baseline measurements of vehicle movements and level crossing status were recorded for two months. Conspicuous cameras and radar were subsequently installed, and a further month of data was recorded. Non-compliances with flashing lights were extracted and arranged into "must stop" and "should stop if safe to do so" categories, aligning with road rules at traffic lights. Non-compliances frequently occurred (N = 1,086) with most (94%) of the latter category and ascribed to a lack of an advanced warning before crossing closure. Analysis with Generalised Linear Models revealed that non-compliances where drivers must stop reduced by 36% (from 13.4% to 8.6%) following the introduction of a conspicuous automated monitoring system, even though no actual enforcement was performed. This study suggests that non-compliances at railway level crossings have the potential to be reduced through the introduction of automated enforcement similar to the one used at traffic lights.


Cognitive behavioral therapy for insomnia combined with eszopiclone for the treatment of sleep disorder patients transferred out of the intensive care unit: A single-centred retrospective observational study.
Patients transferred out of the intensive care unit (ICU) are always impaired by sleep disorders. Cognitive behavioral therapy for insomnia (CBT-I) and eszopiclone are 2 commonly prescribed strategies for insomnia. In the current study, the effect of the combined application of the 2 methods on sleep disorders in ICU transferred out patients was assessed.Twenty-nine insomnia patients receiving combined treatment of CBT-I and eszopiclone and a corresponding number of patients treated with eszopiclone were collected. The incidence of discomfort experiences in ICU was recorded. Polysomnogram (PSG), Pittsburgh Sleep Quality Index (PSQI), self-rating anxiety scale (SAS), self-rating depression scale (SDS), and treatment emergent symptom scale (TESS) were used to assess the treatment efficacy and side effects.Hospitalization for over 7 days, use of benzodiazepines, and experiencing anxiety, insomnia, and mechanical ventilation increased chances of sleep disorders. The sleep latency, awakening time, and total sleep time were further improved in patients treated with the combined therapy than patients treated with eszopiclone (t = -2.334, -2.412, 2.383, P < .05). Similar changing pattern was observed for PSQI score (t = -2.262, P < .05). The improvement effect of the combined therapy on the sleep efficacy, SWS phase III, and rapid eye movement sleep was also significantly stronger (t = 2.112, 2.268, 2.311, P < .05). Moreover, the SAS and SDS scores in patients treated with the combined therapy decreased more than those of patients treated with eszopiclone.The efficacy of CBT-I combined with eszopiclone in the treatment of sleep disorders in ICU transferred out patients was better than eszopiclone.


Massive hematuria due to a congenital renal arteriovenous malformation mimicking a renal pelvis tumor: a case report.
Congenital renal arteriovenous malformations (AVMs) are very rare benign lesions. They are more common in women and rarely manifest in elderly people. In some cases they present with massive hematuria. Contemporary treatment consists of transcatheter selective arterial embolization which leads to resolution of the hematuria whilst preserving renal parenchyma. A 72-year-old man, who was heavy smoker, presented with massive hematuria and flank pain. CT scan revealed a filling defect caused by a soft tissue mass in the renal pelvis, which initially led to the suspicion of a transitional cell carcinoma (TCC) of the upper tract, in view of the patient's age and smoking habits. However a subsequent retrograde study could not depict any filling defect in the renal pelvis. Selective right renal arteriography confirmed the presence of a renal AVM by demonstrating abnormal arterial communication with a vein with early visualization of the venous system. At the same time successful selective transcatheter embolization of the lesion was performed. This case highlights the importance of careful diagnostic work-up in the evaluation of upper tract hematuria. In the case presented, a congenital renal AVM proved to be the cause of massive upper tract hematuria and flank pain in spite of the initial evidence indicating the likely diagnosis of a renal pelvis tumor.


EEG-based detection of emotional valence towards a reproducible measurement of emotions.
A methodological contribution to a reproducible Measurement of Emotions for an EEG-based system is proposed. Emotional Valence detection is the suggested use case. Valence detection occurs along the interval scale theorized by the Circumplex Model of emotions. The binary choice, positive valence vs negative valence, represents a first step towards the adoption of a metric scale with a finer resolution. EEG signals were acquired through a 8-channel dry electrode cap. An implicit-more controlled EEG paradigm was employed to elicit emotional valence through the passive view of standardized visual stimuli (i.e., Oasis dataset) in 25 volunteers without depressive disorders. Results from the Self Assessment Manikin questionnaire confirmed the compatibility of the experimental sample with that of Oasis. Two different strategies for feature extraction were compared: (i) based on a-priory knowledge (i.e., Hemispheric Asymmetry Theories), and (ii) automated (i.e., a pipeline of a custom 12-band Filter Bank and Common Spatial Pattern). An average within-subject accuracy of 96.1 %, was obtained by a shallow Artificial Neural Network, while k-Nearest Neighbors allowed to obtain a cross-subject accuracy equal to 80.2%.


Transarterial chemoembolization for hepatocellular carcinoma after transjugular intrahepatic portosystemic shunt.
The decreased portal blood flow and the potential decrease in arterial nutrient hepatic blood flow after creation of a transjugular intrahepatic portosystemic shunt (TIPS) makes the treatment of hepatocellular carcinoma (HCC) challenging. To evaluate the safety and efficacy of transarterial chemoembolization (TACE) after TIPS in patients with HCC. From 1998 to 2009, 20 patients underwent selective (segmental or subsegmental) TACE for HCC after TIPS. Among 20 patients, seven patients had undergone one to three sessions of TACE for HCC before TIPS creation. TACE was performed using a mixture of iodized oil and cisplatin, and absorbable gelatin sponge particles. Tumor response, complications, and patient survival were evaluated after TACE. After TACE, 14 of the 20 (70%) patients showed a tumor response, with only one (5%) experiencing a TACE-related major complication, spontaneous bacterial peritonitis. None of the patients who underwent TACE after TIPS died within 30 days. During the follow-up period (range 2.2-107 months; mean 32.6 months), 18 patients died and two remained alive. The median survival period after TACE was 23 months. Multivariate Cox regression analysis showed that tumor stage was the only independent prognostic factor for patient survival (P = 0.049). Selective TACE may be safe and effective for the palliative treatment of HCC in patients with TIPS. Late tumor stage ( ≥III) was poor prognostic factor for determining the patient survival period after post-TIPS TACE.


Metabolic profiles of endogenous and ethynyl steroids in plasma and urine from women during administration of oral contraceptives.
Conjugated ethynyl and endogenous steroids in plasma and urine from two women taking an oral contraceptive (Conlumin) containing 1 mg norethindrone and 50 micrograms mestranol have been analyzed by methods based on anion and ligand exchange chromatography and gas chromatography-mass spectrometry. Conjugated norethindrone and its reduced metabolites with 3 alpha,5 alpha, 3 alpha,5 beta, 3 beta,5 beta and 3 beta,5 alpha configurations were identified in the fluids. The quantitatively major metabolites in plasma were a disulphate of the 3 alpha,5 alpha isomer and a monosulphate of the 3 alpha,5 beta isomer. The renal clearance of the former compound was low. The major urinary metabolite of norethindrone was the 3 alpha,5 beta isomer conjugated with glucuronic or sulphuric acid. Disulphates constituted only a small portion of urinary ethynyl steroids. Metabolic profiles of endogenous neutral steroids in plasma and urine during the contraceptive cycle were compared with profiles during a physiological menstrual cycle. The concentrations of steroids in plasma during contraception were similar to those during the follicular and mid phases of the menstrual cycle, whereas levels of progesterone metabolites were higher in the luteal phase. The urinary excretion of steroids was 15-30% lower during the contraceptive cycle, due to a decrease in excretion of C21O5 steroids, 11-oxygenated androgens and etiocholanolone. The increase of urinary progesterone metabolites seen during the luteal phase was not observed during contraception, but the excretion of 5 beta-pregnane-3 alpha,20 alpha-diol glucuronide was higher than during the follicular and mid phases of the menstrual cycle.


Genetic diversity and structure revealed by genomic microsatellite markers in Centella asiatica (L.) Urb., a plant with medicinal potential.
Around the world, medicinal plants are utilised for various purposes. Centella asiatica is one of the important medicinal plants widely used in many medicinal systems. Nevertheless, analysis of the genetic diversity would pave the way for its most suitable utilisation. The present study analyses the genetic diversity and structure of eighty C. asiatica accessions collected from the southern states of India, using ten genomic microsatellite markers. The mean Nei's gene diversity (0.46) indicates considerable genetic diversity. Analysis of molecular variance (82.48%) exhibited significant genetic variance between samples within the population. The cluster analysis brought out the structure of the analysed populations as three subpopulations based on the genetic differentiation. The study showed significant intra-population variation, predominant inbreeding and population differentiation in C. asiatica. The findings will help better understanding of the genetic structure and gene pool of the plant.


HSP90 inhibition: two-pronged exploitation of cancer dependencies.
The early clinical hypothesis for inhibiting HSP90 in cancers was based on the dependence of certain key client proteins in malignant cells--including a host of well-characterized oncoproteins--on the activity of HSP90 for their function and stability. The additional concept has been established that cancer cells have heightened dependence on the efficient maintenance of intracellular proteomic homeostasis, central components of which are HSP90 and other heat shock proteins. We evaluate the evidence that inhibiting HSP90 in cancer exploits both of these biological vulnerabilities very effectively, we review the current status of the discovery and development of HSP90 inhibitors and we identify routes to improve their clinical efficacy, based on emerging knowledge.


Are sleep continuity disturbance and fatigue prodromal symptoms of cancer development?
Sleep continuity disturbance (also known as insomnia) and fatigue are common complaints of individuals diagnosed with cancer. Traditionally, many have believed that sleep continuity disturbance and fatigue are caused, in large measure, by the impact of the cancer diagnosis and treatment. Recent prospective research suggests however, that sleep continuity disturbance and fatigue may actually precede a cancer diagnosis. We suggest that sleep continuity disturbance and fatigue may in fact represent prodromal symptoms of cancer. We review the current perspectives of this sequence of events and present a revised schematic that accounts for the role of biological, behavioural, and cognitive factors that contribute to the development and maintenance of sleep continuity disturbances in cancer patients. Monitoring emergent and unexplained patient-reported fatigue, sleepiness, and insomnia may serve as early warning signs of new onset cancer, providing opportunity for early detection and early intervention.


The Role of CT Angiography to Predict the Shamblin Group in Carotid Body Tumors.
Carotid body tumors (CBTs) are uncommon benign head and neck neoplasms. Surgical resection is the treatment of choice for CBTs. However, the anatomical structures adjacent to the tumor tissue may encounter serious injuries during the surgery. Shamblin grading system is a surgical intra-operative scoring system to determine the risks associated with the surgery. Therefore, we aimed to evaluate the correlation of pre-surgical imaging parameters with Shamblin grades and intra-operative complications. In this cross sectional study, we enrolled 36 patients with CBTs. Preoperative cervical CT angiography was acquired in each participant and following parameters were reported in each case: Tumor volume, tumor distance to the base of the skull (TDBS), tumor contact with the internal carotid artery (ICA), and external carotid artery (ECA) and tumor density. Finally, we assessed the relation of pre-surgical imaging parameters with Shamblin grades, and intra-operative complications. Only tumor volume was significantly correlated with Shamblin grades (P < 0.05). The tumor contact with ECA was marginally correlated with Shamblin grades (P = 0.103); however, other imaging parameters were not significantly correlating with Shamblin grades. There was a statistically significant correlation between ICA contact and tumor volume with ECA injury. In addition, the tumor density significantly correlated with cranial nerves injury. The results of STATA analysis were indicative for 69.44% accordance between radiologic typing and Shamblin grading system. We found that tumor volume correlates significantly with Shamblin grading system, and there is significant correlation between tumor ICA contact, and tumor density and intra-operative complications.


The effects of trichostatin A on the oncolytic ability of herpes simplex virus for oral squamous cell carcinoma cells.
Combining the use of a chemotherapeutic agent with oncolytic virotherapy is a useful way to increase the efficiency of the treatment of cancer. The effect of the histone diacetylase (HDAC) inhibitor trichostatin A (TSA) on the antitumor activity of a herpes simplex virus type-1 (HSV-1) mutant was examined in oral squamous cell carcinoma (SCC) cells. Immunoblotting analysis and immunoflourescence staining revealed that a cytoplasmic nuclear factor-kappaB (NF-kappaB) component, p65, translocated into the nucleus after infection with gamma(1)34.5 gene-deficient HSV-1 R849, indicating that R849 activated NF-kappaB. TSA induced acetylation of p65 and increased the amount of p65 in the nucleus of oral SCC cells. Treatment of R849-infected cells with TSA also increased the amount of nuclear p65 and binding of NF-kappaB to its DNA-binding site and an NF-kappaB inhibitor SN50 diminished the increase in nuclear p65. In the presence of TSA, the production of virus and the expression of LacZ integrated into R849 and glycoprotein D, but not ICP0, ICP6 and thymidine kinase, were increased. The viability of cells treated with a combination of R849 and TSA was lower than that of those treated with R849 only. After treatment with TSA, expression of the cell cycle kinase inhibitor p21 was upregulated and the cell cycle was arrested at G1. These results indicate that TSA enhanced the replication of the HSV-1 mutant through the activation of NF-kappaB and induced cell cycle arrest at G1 to inhibit cell growth. TSA can be used as an enhancing agent for oncolytic virotherapy for oral SCC with gamma(1)34.5 gene-deficient HSV-1.


"Neural" responses to acoustic stimulation after destruction of cochlear hair cells.
Electrophysiological and histological observations in guinea pig's cochleas after amikacin treatment (14 X 450 mg/kg) confirm the results obtained in a former experiment: clear, short-latency, click-evoked responses were recorded in cochleas with only very few hair cells remaining at the extreme apex. Detailed analysis of these responses strongly indicates a neural origin and confirms their low-frequency sensitivity. Careful histological observations confirm the extensive hair cell loss and the preservation of nerve fibers in the remnants of the organ of Corti and of the vestibular sense organs. These results suggest that the acoustical vibrations either stimulate the vestibular receptors or act directly or through some kind of mechano-electrical transduction on the remaining cochlear nerve fibers.


Geographic redistribution of practice location of graduate dentists: a six-year retrospective analysis (2004-2009).
The purpose of this study was to analyse the geographic distribution of practice locations of graduate dentists from the University of Western Australia (UWA) over a period of six years. Using data from open access sources, all practice locations of the UWA's dental graduates from 2004 to 2009 were located. All practice locations were measured at the postcode level and the distribution of graduates was analysed across variables such as SEIFA (a socio-economic index of disadvantage) and ARIA (an index of accessibility and remoteness). Of the 228 UWA graduates, an almost equal proportion of males (49.1%) and females (50.9%) graduated over the six-year period. Of all the local graduates, 83% continued to practice in Western Australia, with 78% of the practice locations alone in ARIA 1 (highly accessible areas) and 22% of the graduates distributed among the remaining ARIA regions. Fifty-one per cent of graduates practised in the 30% most affluent suburbs and only 11.5% practised in the most socio-economically disadvantaged 30% suburbs. In SEIFA decile 10 (least disadvantaged areas), the highest numbers of practising dental graduates were also from the earliest graduates, with numbers steadily declining over the year of graduation from 2004 to 2009 (i.e. the most recent graduates). An apparent association exists between year of graduation and practice location, with more experienced dentists working in urban and higher socio-economic areas.


Chitosan/gellan gum ratio content into blends modulates the scaffolding capacity of hydrogels on bone mesenchymal stem cells.
Here, we have demonstrated the production and characterization of hydrogel scaffolds based on chitosan/gellan gum (CS/GG) assemblies, without any covalent and metallic crosslinking agents, conventionally used to yield non-soluble polysaccharide-based materials. The polyelectrolyte complexes (physical hydrogels called as PECs) are characterized by Fourier-transform infrared spectroscopy, wide-angle X-ray scattering, and scanning electron microscopy. Hydrogels containing chitosan (CS) excesses (ranging from 60 to 80 wt%) were created. Durable polysaccharide-based scaffolds with structural homogeneity and interconnecting pore networks are developed by modulating the CS/GG weight ratio. The CS/GG hydrogel prepared at 80/20 CS/GG weight ratio (sample CS/GG80-20) is cytocompatible, supporting the attachment, growth, and spreading of bone marrow mesenchymal stem cells (BMSCs) after nine days of cell culture. The cytocompatibility is correlated to the swelling capacity of the PEC in PBS buffer (pH 7.4). By controlling the CS content, we can tune the water uptake of the material, enhancing the capacity to serve as a three-dimensional cell scaffold for BMSCs. This work presents for the first time that CS/GG hydrogels can be applied as scaffolds for tissue engineering purposes.


The influence of knowledge, perceptions, and beliefs, on hand hygiene practices in nursing homes.
There are few studies that have assessed factors influencing infection control practices among health care workers (HCW) in nursing homes. We conducted a cross-sectional survey of HCWs (N = 392) in 4 nursing homes to assess whether knowledge, beliefs, and perceptions influence reported hand hygiene habits. Positive perceptions and beliefs regarding effectiveness of infection control in nursing homes were associated with reported appropriate glove use and fingernail characteristics, respectively, among HCWs. Further research on hand hygiene interventions, including targeted educational in-services should be conducted in the nursing home setting.


Geriatric Nutritional Risk Index can predict postoperative delirium and hospital length of stay in elderly patients undergoing non-cardiac surgery.
Malnutrition is common in older patients and is associated with adverse outcomes. The Geriatric Nutritional Risk Index (GNRI) has been developed as an objective index to assess nutritional risk in these patients. However, there is limited evidence regarding the association between GNRI and postoperative delirium (POD) as well as length of stay (LOS) in surgical older patients. Therefore, our goal was to examine the impact of poor nutrition, evaluated by the GNRI, on POD and length of stay in older patients undergoing non-cardiac surgery. In this prospective cohort study, older patients undergoing non-cardiac surgery from April to June of 2015 were included. Preoperative nutritional status was assessed by the GNRI within the first 48 h after hospital admission. The outcomes were POD and LOS. Multivariable logistic regression and linear regression analyses were used to assess the role of GNRI in predicting these outcomes. In the whole sample (N = 288), the prevalence of severe/moderate (GNRI <92) and low (GNRI 92-98) nutritional risk was 15.6% and 29.5%, respectively. The median length of hospital stay was 14 days. Delirium was present in 49 patients (17%). A linear regression analysis showed that low (β = 4.56, 95% confidence interval [CI]: 2.18-6.94) and severe/moderate (β = 3.70, 95% CI: 0.74-6.65) nutritional risk were associated with prolonged LOS. Moreover, a multivariate analysis revealed that patients with severe/moderate nutritional risk were more likely to develop POD compared with those without (odds ratio = 2.56, 95% CI: 1.11-5.89). Preoperative malnutrition, as assessed using the GNRI, predicted LOS and the development of POD in elderly non-cardiac surgical patients. Geriatr Gerontol Int 2020; 20: 759-764.


Broad host tropism of ACE2-using MERS-related coronaviruses and determinants restricting viral recognition.
Recently, two Middle East respiratory syndrome coronavirus (MERS-CoV) closely related to bat merbecoviruses, NeoCoV and PDF-2180, were discovered to use angiotensin-converting enzyme 2 (ACE2) for entry. The two viruses cannot use human ACE2 efficiently, and their host range and cross-species transmissibility across a wide range of mammalian species remain unclear. Herein, we characterized the species-specific receptor preference of these viruses by testing ACE2 orthologues from 49 bats and 53 non-bat mammals through receptor-binding domain (RBD)-binding and pseudovirus entry assays. Results based on bat ACE2 orthologues revealed that the two viruses were unable to use most, but not all, ACE2 from Yinpterochiropteran bats (Yin-bats), which is distinct from NL63 and SARS-CoV-2. Besides, both viruses exhibited broad receptor recognition spectra across non-bat mammals. Genetic and structural analyses of bat ACE2 orthologues highlighted four crucial host range determinants, all confirmed by subsequent functional assays in human and bat cells. Notably, residue 305, participating in a critical viral receptor interaction, plays a crucial role in host tropism determination, particularly in non-bat mammals. Furthermore, NeoCoV and PDF-2180 mutants with enhanced human ACE2 recognition expanded the potential host range, especially by enhancing their interaction with an evolutionarily conserved hydrophobic pocket. Our results elucidate the molecular basis for the species-specific ACE2 usage of MERS-related viruses and shed light on their zoonotic risks.


Exploring influential factors of CO2 emissions in China's cities using machine learning techniques.
The precise and exhaustive discernment of factors influencing CO2 emissions underpins the advancement toward sustainable, low-carbon development. Although numerous studies have probed the correlation between predetermined proxy variables and carbon emissions, methodological constraints have often led to an inability to effectively discern carbon emission determinants among numerous potential variables or unravel complex, non-linear relationships, and interaction effects. To redress these research gaps, this research utilized machine learning models to correlate urban CO2 emissions with socioeconomic indicators. The model outputs were then visualized and interpreted using explainable methods. The findings indicated that the model successfully identified a comprehensive array of dominant influences on urban CO2 emissions, principally associated with local fiscal policies, land use, energy consumption, industrial development, and urban transportation. The findings further revealed a complex non-linear association between these factors and urban CO2 emissions; however, the majority of these variables displayed a prevalent propensity to intensify carbon emissions in correspondence with an increase in sample value. Additionally, these factors exhibited a complex interactive influence on urban CO2 emissions, with distinct pairings producing a suppressive effect exclusively at specific combination of sample values. Consequently, this research posited that a robust correlation between urban socioeconomic development and CO2 emissions in China remains to be established. Given the varied impacts of these influencing factors across different cities, a differentiated approach to development should be adopted when charting low-carbon trajectories.


Eightfold induction of nicotine elimination in perfused rat liver by pretreatment with phenobarbital.
Elimination of nicotine by isolated rat livers was increased eightfold after pretreatment with phenobarbital (PB) as an inducer of cytochrome P-450 while it was only marginally influenced after pretreatment with 5,6-benzoflavone (BF) as an inducer of cytochrome P-448. Initial rates of cotinine formation were enhanced in the same order of magnitude in PB-induced livers. The 14C-nicotine-derived radioactivity excreted into bile within 2 h ranged between 6 -17% of the dose with only 2.7 fold higher values after PB pretreatment compared to controls.


The potential of miR-153 as aggressive prostate cancer biomarker.
Prostate cancer (PC) is one of the most frequently diagnosed cancers in males. MiR-153, as a member of the microRNA (miRNA) family, plays an important role in PC. This study aims to explore the expression and possible molecular mechanisms of the miR-153 action. Formalin-fixed paraffin-embedded (FFPE) tissues were collected from prostatectomy specimens of 29 metastatic and 32 initial stage PC patients. Expression levels of miR-153 were measured using real-time reverse transcription polymerase chain reaction (qRT-PCR). 2-ΔΔCT method was used for quantitative gene expression assessment. The candidate target genes for miR-153 were predicted by TargetScan. Mutations in target genes of miR-153 were identified using exome sequencing. Protein-protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the potential molecular mechanisms of miR-153 in PC. MiR-153 was significantly up-regulated in PC tissues compared to non-cancerous tissues. The analysis of correlation between the expression level of miR-153 and clinicopathological factors revealed a statistically significant correlation with the stage of the tumor process according to tumor, node, metastasis (TNM) staging system (p = 0.0256). ROC curve analysis was used to evaluate the predictive ability of miR-153 for metastasis development and it revealed miR-153 as a potential prognostic marker (AUC = 0.85; 95%CI 0.75-0.95; sensitivity = 0.72, specificity = 0.86)). According to logistic regression model the high expression of miR-153 increased the risk of metastasis development (odds ratios = 3.14, 95% CI 1.62-8.49; p-value = 0.006). Whole exome sequencing revealed nonsynonymous somatic mutations in collagen type IV alpha 1 (COL4A1), collagen type IV alpha 3 (COL4A3), forkhead box protein O1 (FOXO1), 2-hydroxyacyl-CoA lyase 1 (HACL1), hypoxia-inducible factor 1-alpha (HIF-1A), and nidogen 2 (NID2) genes. Moreover, KEGG analysis revealed that the extracellular matrix-receptor (ECM-receptor) interaction pathway is mainly involved in PC. MiR-153 is up-regulated in PC tissues and may play an important role in aggressive PC by targeting potential target genes.


Influence of branched-chain amino acid composition of culture media on the synthesis of plasma proteins by serum-free cultured rat hepatocytes.
Supplementation of Ham's F12 culture medium with essential amino acids (EAA) up to the rat plasma levels increased the rates of synthesis of albumin and transferrin by cultured rat hepatocytes by 1.3 and 1.7, respectively. Fifty percent of this increase could be attributed to three of the EAA: the branched-chain amino acids (BCAA: Leu Ile and Val). Non-branched-chain essential amino acids (non-BC-EAA) stimulated only 25% of the increase produced by the whole EAA mixture. When each EAA was tested individually, none of them caused an appreciable increase in albumin and transferrin in culture medium. When the concentrations of all EAA were raised to rat postprandial portal levels, albumin and transferrin synthesis rates reached a maximum, increasing by 3.2 and 3.5, respectively. Supplementation with BCAA at postprandial portal concentrations increased albumin and transferrin synthesis rates by 2.2 and 2.0, respectively, and had no noteworthy effect on the synthesis of cellular proteins. Non-BC-EAA at their postprandial portal concentrations increased albumin and transferrin synthesis rates by 1.7 and 1.9, respectively. Supplementation with alanine to reach a nitrogen content equal to that of the modified EAA-enriched medium had no stimulatory effect. Our results show that EAA have a specific effect on the synthesis of plasma proteins by cultured hepatocytes, and that BCAA at physiologic concentrations account for the major part of this stimulatory effect. Consequently, EAA and particularly BCAA concentration should be elevated in serum-free nutrient media to sustain maximum plasma protein synthesis.


Kinetics of erythroid and myeloid stem cells in post-hypoxia polycythaemia.
The number of erythroid burst-(BFU-E) and colony-forming units (CFU-E), as well as of myeloid-macrophage colony-forming units (CFU-C), has been evaluated in tibial marrow and spleen of ex-hypoxic polycythaemic mice, at sequential time intervals after the end of hypoxia. In both marrow and spleen, the kinetics of the CFU-E pool is characterized by a sharp fall from above normal to lower than normal values. BFU-E and CFU-C however rise from below normal to higher than normal levels. These results have been correlated with both the erythropoietin (Ep) and the erythropoietic activity curves. It is apparent that Ep levels largely control both the differentiation and the amplification of the CFU-E pool and it is suggested that Ep may act as a 'survival factor' at the CFU-E level and/or increase the flow of cells from BFU-E to CFU-E. The difference in response between CFU-E and BFU-E favours a clearcut distinction between these populations, whereas the similarity between the BFU-E and CFU-C response suggest a close relationship between these two cell populations. It is also of interest that the murine spleen functions as a large reservoir of erythroid microenvironment for hypoxia-induced stress erythropoiesis.


Third-generation slotplates for orthognathic and facial corrective surgery.
The aim of this study was to retrospectively assess the osteosynthesis material-related morbidity rates of third-generation (3.0) slotplates, and to compare those with the previously researched second-generation (2.0) slotplates. In the 2.0 slotplate design, there were additional tabs in line with the vertical slotted screw hole; in between these tabs, the additional locking screw was placed. In the 3.0 slotplates, these tabs were replaced by a full screw hole for the locking screw, and the 3.0 slotplates are slightly broader than the 2.0 slotplates. Osteosynthesis material-related morbidity rates after Le Fort I-type, zygoma-valgisation, and chin osteotomies were assessed in a cohort receiving 3.0 slotplates in a tertiary care centre and compared to a previously analysed cohort receiving 2.0 slotplates in the same tertiary care centre. Medical records of 77 patients (101 surgeries) receiving 3.0 slotplates were reviewed. Plate infection and plate removal rates were low in the 3.0 slotplate group (2.6% (p = 0.123) and 3.9% (p = 0.103), respectively). No delayed union or non-union occurred in the 3.0 slotplate group. Comparing the morbidity rates with the 2.0 slotplate cohort did not yield any significant differences. Although there was a tendency towards better outcomes with 3.0 slotplates compared to the 2.0 slotplates, the outcome differences did not reach statistical significance.


The IRAK-1-BCL10-MALT1-TRAF6-TAK1 cascade mediates signaling to NF-kappaB from Toll-like receptor 4.
Our previous studies have revealed that the signaling protein BCL10 plays a major role in adaptive immunity by mediating NF-kappaB activation in the LPS/TLR4 pathway. In this study, we show that IRAK-1 acts as the essential upstream adaptor that recruits BCL10 to the TLR4 signaling complex and mediates signaling to NF-kappaB through the BCL10-MALT1-TRAF6-TAK1 cascade. Following dissociation from IRAK-1, BCL10 is translocated into the cytosol along with TRAF6 and TAK1, in a process bridged by a direct BCL10-Pellino2 interaction. RNA interference against MALT1 markedly reduced the level of NF-kappaB activation stimulated by lipopolysaccharide (LPS) in macrophages, which suggests that MALT1 plays a major role in the LPS/TLR4 pathway. MALT1 interacted with BCL10 and TRAF6 to facilitate TRAF6 self-ubiquitination in the cytosol, which was strictly dependent on the dissociation of BCL10 from IRAK-1. We show that BCL10 oligomerization is a prerequisite for BCL10 function in LPS signaling to NF-kappaB and that IRAK-1 dimerization is an important event in this process.


Ratiometric fluorescence detection of ciprofloxacin using the terbium-based coordination polymers.
Herein, a facile self-assembly through adenosine monophosphate (AMP) and luminol with Tb3+ was employed to construct a dual-ligand coordinated AMP-Tb-luminol coordination polymers (CPs), which emitted the typical fluorescence of luminol. Based on the sensitization effect of ciprofloxacin (CIP) on the luminescence of Tb3+, a ratiometric sensor was fabricated using the fluorescence of luminol as an inert reference. The fluorescent intensity ratios of Tb3+ to that of luminol enhanced linearly with the CIP concentration in the range from 5 nM to 2.5 μM with a lower limit of detection of 2 nM. In addition, the proposed ratiometric fluorescent sensor exhibited high selectivity for CIP, which could also be used to detect CIP in human blood serum (HBS) with satisfactory results. To our knowledge, this is the first demonstration of using dual-ligand coordination lanthanide (Ln)-based CPs for ratio-metric CIP assay, and this straightforward strategy may open up a new platform for designing the ratio-metric sensors based on the Ln CPs.


Dynamics of microbial populations and strong selection for Cycloclasticus pugetii following the Nakhodka oil spill.
Microbial population changes were monitored immediately after the Nakhodka oil spill accident in January 1997 at the heavily oil-contaminated Mikuni coast along the Sea of Japan. The total cell number was almost stable for one year at 2-5 x 10(5) cells mL(-1), while the relative occurrence of culturable heterotrophs and degraders of oil components such as C-heavy oil, kerosene, and n-tetradecane varied, showing a maximum (>50% of the total) immediately following the accident. Gene amplification and phylogenetic analysis of a dilution culture using C-heavy oil as the sole carbon and energy source revealed that one of the predominant oil degraders at the oil-contaminated coast in 2 weeks after the accident closely resembled the aromatic hydrocarbon decomposer Cycloclasticus pugetii. Microbial community composition in oil-contaminated seawater was estimated at the molecular level using newly developed oligonucleotide probes, probe wash-off curve estimation, and quantitative fluorescence dot-blot hybridization techniques. At two different oil-polluted sites, harbor and intertidal regions, the C. pugetii group was estimated to make up 23-25% of the total Bacteria population, followed by the aliphatic hydrocarbon decomposer Alcanivorax borkumensis, which formed 4-7% of the Bacteria. In incubation experiments using floated oil slick and indigenous microbes collected at the harbor, oil degradation activities were enhanced by the addition of both organic and inorganic nutrients. Significant decreases were found in aromatic and aliphatic hydrocarbon fractions: 54-60% and 22-24% in 2 weeks to 68-77% and 23-32% in 2 months, respectively.


Quantitative immunocytochemistry of tyrosine hydroxylase in rat brain. II. Variations in the amount of tyrosine hydroxylase among individual neurons of the locus coeruleus in relationship to neuronal morphology and topography.
We sought to determine by a computer assisted quantitative immunocytochemical method using the peroxidase-antiperoxidase (PAP) technique if individual neurons of the nucleus locus coeruleus (LC) varied with respect to the amount of tyrosine hydroxylase (TH) within each cell and, if so, whether the amount of TH is related to morphometric characteristics and/or location of the neuron within the LC. Appropriate immunohistochemical reaction conditions were used so that the intensity of DAB reaction product formed in the PAP reaction was directly and linearly related to the amount of TH enzyme protein present in the tissue. The distribution of the average optical density of 1425 individual LC neurons obtained from 5 animals and standardized to an overall mean density varies unimodally over a 3-fold range. The relationship between staining intensity and morphological and topographic characteristics of individual neurons was examined. There was no correlation between staining intensity and morphological features of individual neurons, including cytoplasmic area. However, differences in the amount of TH in individual neurons correlated significantly (P less than 0.01) with the location of the cell in LC: the lightest staining neurons were located in the central core of the LC. The density of staining did not differ significantly in the other 4 traditionally defined regions of LC (the anterior, posterior, and ventral poles of the LC and the nucleus subcoeruleus) which form a rim around the central core. Similarly, cells which are closest to the center of mass of the LC showed a lighter staining intensity than cells located progressively further from the center. These lighter staining cells in the center were also packed more closely together (P less than 0.01). Therefore dense packing of neurons correlates with light staining intensity (P less than 0.01). We conclude that neurons of the LC vary with respect to the amount of TH, which in turn relates to the location of the cell in the LC and possibly its packing density, but not its morphometric characteristics. Since in noradrenergic neurons, the amount of TH is directly influenced by firing rate, the results suggest that the biochemical heterogeneity of LC neurons reflects differences in their functional activities. In turn, this may relate to heterogeneity of LC with respect to projection fields.


Expression of cell cycle associated proteins influences radiocurability of T2N0 squamous cell carcinoma of the larynx.
Cell cycle modulators are important in carcinogenesis and may be of prognostic and therapeutic relevance. This study has examined the influence of the proliferation index (Ki-67) and immunocytochemical expression of epidermal growth factor receptor (EGFR), cyclin D1, and retinoblastoma protein on recurrence rates at the primary site in 50 patients with T2N0 laryngeal carcinomas treated with radical irradiation. Pre-treatment biopsies were retrieved and sections scored for the four immunocytochemical markers. Statistical analysis for association, interaction and survival was performed. Five cases showed loss of expression of Rb protein. The median Ki-67 index was 50%, the median cyclin D1 index 21% and the median EGFR index 47% of cells. EGFR and cyclin D1 expression were positively correlated and, whilst local recurrence tended to occur with a Ki-67 labelling index of <50%, this was not statistically significant. When interactions were examined using Multiple Logistic Regression it was found that there was a direct relationship between EGFR and cyclin D1 expression. If the EGFR index was >20% and the cyclin D1 index >10%, then the odds ratio in favour of a primary site recurrence was very high (5.32 +/-0.41). This study demonstrates that the relationship between EGFR index and cyclin D1 index has a very strong association with primary site recurrence for T2 N0 laryngeal carcinomas treated by irradiation.


The statistical mechanics of felt uncertainty under active inference.
Convincing narratives are not confabulations. Presumably they "feel right" to decision-making agents because the probabilities they assign intuitively (i.e., implicitly) to potential outcomes are plausible. Can we render explicit the calculations that would be performed by a decision-making agent to evaluate the plausibility of competing narratives? And if we can, what, exactly, makes a narrative "feel right" to an agent?