ANTHELMINTIC ACTIVITY OF CHLOROPHYLLIN AGAINST DIFFERENT LARVAL STAGES OF Fasciola gigantica.
Fasciolosis is a food borne zoonosis, caused by the digenetic trematode Fasciola. Freshwater lymnaeid snails are the intermediate host of the trematodes. Chlorophyllin, a semi-synthetic derivative of chlorophyll and its formulations obtained from freeze dried cow urine (FCU) had their toxicity tested against redia and cercaria larvae of F. gigantica. The larvicidal activity of chlorophyllin and its formulations were found to depend on both, time and concentration used against the larvae. Toxicity of chlorophyllin + FCU (1:1 ratio) in sunlight against redia larva (8 h LC50: 0.03 mg/mL) was more pronounced than using just chlorophyllin (8 h LC50: 0.06 mg/mL). Toxicity of chlorophyllin + FCU in sunlight against redia (8 h LC50: 0.03 mg/mL) was higher than against cercaria (8 h LC50: 0.06 mg/mL). The larvicidal activity of chlorophyllin in sunlight (redia/cercaria larvae: 8 h LC50: 0.06 mg/mL) was more pronounced than under laboratory conditions (redia: 8 h LC50: 22.21 mg/mL/, cercaria 8 h LC50: 96.21 mg/mL). Toxicity of FCU against both larvae was lower than that of chlorophyllin and chlorophyllin + FCU. Chlorophyllin and its formulations + FCU were 357.4 to 1603.5 times more effective against redia/cercaria larvae in sunlight than under laboratory conditions. The present study has shown that chlorophyllin formulations may be used as potent larvicides against fasciolosis.


Microscopic formulation of the Zimm-Bragg model for the helix-coil transition.
A microscopic spin model is proposed for the phenomenological Zimm-Bragg model for the helix-coil transition in biopolymers. This model is shown to provide the same thermophysical properties of the original Zimm-Bragg model and it allows a very convenient framework to compute statistical quantities. Physical origins of this spin model are made transparent by an exact mapping into a one-dimensional Ising model with an external field. However, the dependence on temperature of the reduced external field turns out to differ from the standard one-dimensional Ising model and hence it gives rise to different thermophysical properties, despite the exact mapping connecting them. We discuss how this point has been frequently overlooked in the recent literature.


Superolateral pedicle for breast surgery: an operation for all reasons.
The evolution of procedures for reduction of breast volume and improvement of breast shape has been ongoing, based on the rich blood supply that has allowed a plethora of pedicle types. With particular consideration of the primary pattern of sensory innervation to the nipple-areola complex previously described, the authors have used the superolateral dermoparenchymal pedicle as a basis for surgery on a variety of presenting breast shapes. This has been proven to be a versatile and effective technique for a wide array of breast morphologies with differing patterns of skin excision. The operative technique involves superior rotation of a superolaterally based dermoparenchymal pedicle, resulting in a "periwinkle" effect that provides desirable superior pole fullness and increased projection to the breast. More than 1500 breast procedures have been performed by the senior author (Strauch) during the past 15 years using the superolateral pedicle. Experience has demonstrated that the operation is safe, with total nipple-areola complex loss observed in only four cases. Long-term follow-up to 15 years has shown that the results are maintained well with time. The superolateral dermoparenchymal pedicle has fulfilled the goals of successful breast surgery. It is a safe and effective technique that has provided long-lasting results for patients. The design of the procedure can be adapted to a variety of skin excision patterns and breast morphologies.


An integrated experimental-computational approach for predicting virulence in New Zealand white rabbits and humans following inhalation exposure to Bacillus anthracis spores.
Inhalation of Bacillus anthracis spores can lead to an anthrax infection that can be fatal. Previously published mathematical models have extrapolated kinetic rates associated with bacterial growth in New Zealand White (NZW) rabbits to humans, but to date, actual measurements of the underlying processes associated with anthrax virulence between species have not been conducted. To address this knowledge gap, we have quantified species-specific rate constants associated with germination, proliferation, and immune cell inactivation of B. anthracis Sterne using an in vitro test platform that includes primary lung epithelial and immune cells. The generated data was then used to develop a physiologically based biokinetic model (PBBK) which quantitatively compares bacterial growth and mean time to death under lethal conditions in rabbits and humans. Simulations based upon our in vitro data and previously published in vivo data from rabbits indicate that disease progression is likely to be faster in humans than in NZW rabbits under comparable total deposited dose conditions. With the computational framework established, PBBK parameters can now be refined using experimental data for lethal B. anthracis strains (e.g. Ames) under identical conditions in future studies. The PBBK model can also be linked to existing aerosol dosimetry models that account for species-specific differences in aerosol deposition patterns to further improve the human health risk assessment of inhalation anthrax.


Quality of care after ostomy surgery: a perspective study of patients.
Ostomy surgery affects life on a variety of levels. Clinicians need to facilitate the patient's adaptation to life with a stoma and provide information and support to ease the transition. To prospectively assess ostomy patients' perceptions of the quality of care received as well as the importance they ascribe to care conditions, 49 patients from nine Swedish hospitals completed a postoperative "Quality of Care from the Patient's Perspective" questionnaire modified to include stoma care variables. The questionnaire consists of 49 items covering 17 quality dimensions factors that address medical-technical competence, physical-technical conditions, identity-oriented approach, and socio-cultural atmosphere. The modified version contains an additional 13 ostomy-specific items that have demonstrated face validity. Responses to questions were provided using 4-point scales to assess perceived reality and subjective importance. "Medical treatment" received the highest score on the perceived reality scale; "interest in view-of-life," "care-room characteristics," and "participation" received the lowest scores. On the ostomy-specific section, patients were satisfied with most aspects of care received; "where to get advice and support concerning the ostomy" received the highest score. "Talking about sexuality with the ET nurse" received the lowest score on both perceived reality and subjective importance scales. Although the majority of patients regarded most aspects of care as important and were highly satisfied with the care they received before and following their ostomy surgeries, periodic follow-up will most likely enhance satisfaction and long-term follow-up results may differ from those obtained shortly after surgery.


Impact of Pretreatments and Drying Temperatures on Quality of Siwi and Sakkoti Dates.
Drying of date helps in preserving it to be consumed outside the harvest season and removes some moisture from dates and also slows down the action of date endogenous enzymes. This study was carried out to investigate pretreatments and drying temperature on the physical and chemical properties of 2 date varieties (Siwi and Sakkoti) at the khalal stage. The date fruits at khalal stage were dipped in ascorbic acid solution, sodium metabisulfite solution and sulfur dioxide before cut into pieces, halves and as whole. Then dates were dried at 50, 55, 60 and 65°C, respectively till ~20% moisture content and examined the physical and chemical properties of dried dates. Moisture content of Siwi and Sakkoti at the khalal stage was 56.90 and 51.72%, respectively, while total sugars were 79.76 and 75.74%, respectively on dry weight bases. The color of dates Hunter (L and b) were the highest of treated with meta-bisulfate solution or sulfur dioxide and the lowest of color date observed (Hunter, a) comparing with control and ascorbic acid. The pretreatments indicated that the dipping dates in sodium meta-bisulfate solution or sulfur dioxide then, dried at 60˚C produce high quality parameters of semi-dry dates comparing control and ascorbic acid.


Formylglycine, a post-translationally generated residue with unique catalytic capabilities and biotechnology applications.
Formylglycine (fGly) is a catalytically essential residue found almost exclusively in the active sites of type I sulfatases. Formed by post-translational oxidation of cysteine or serine side chains, this aldehyde-functionalized residue participates in a unique and highly efficient catalytic mechanism for sulfate ester hydrolysis. The enzymes that produce fGly, formylglycine-generating enzyme (FGE) and anaerobic sulfatase-maturating enzyme (anSME), are as unique and specialized as fGly itself. FGE especially is structurally and mechanistically distinct, and serves the sole function of activating type I sulfatase targets. This review summarizes the current state of knowledge regarding the mechanism by which fGly contributes to sulfate ester hydrolysis, the molecular details of fGly biogenesis by FGE and anSME, and finally, recent biotechnology applications of fGly beyond its natural catalytic function.


Is gingival bleeding a symptom of type 2 and 3 von Willebrand disease?
Von Willebrand disease (VWD) is the most common inherent bleeding disorder. Gingival bleeding is a frequently reported symptom of VWD. However, gingival bleeding is also a leading symptom of plaque-induced gingivitis and untreated periodontal disease. In type 1 VWD gingival bleeding was not increased compared to controls. Thus, this study evaluated whether type 2 and 3 VWD determines an increased susceptibility to gingival bleeding in response to the oral biofilm. Twenty-four cases and 24 controls matched for age, sex, periodontal diagnosis, number of teeth and smoking were examined hematologically (VWF antigen, VWF activity, factor VIII activity) and periodontally (Gingival Bleeding Index [GBI]), bleeding on probing [BOP], Plaque Control Record [PCR], periodontal inflamed surface area [PISA], vertical probing attachment level). BOP (VWD: 14.5±10.1%; controls: 12.3±5.3%; p = 0.542) and GBI (VWD: 10.5±9.9%; controls: 8.8±4.8%; p = 0.852) were similar for VWD and controls. Multiple regressions identified female sex, HbA1c, PCR and PISA to be associated with BOP. HbA1c and PCR were associated with GBI. Number of remaining teeth was negatively correlated with BOP and GBI. Type 2 and 3 VWD are not associated with a more pronounced inflammatory response to the oral biofilm in terms of BOP and GBI.


Scalable Fabrication of Polymeric Composite Microspheres to Inhibit Oral Pathogens and Promote Osteogenic Differentiation of Periodontal Membrane Stem Cells.
Periodontitis is a worldwide bacterial infectious disease, resulting in the resorption of tooth-supporting structures. Biodegradable polymeric microspheres are emerging as an appealing local therapy candidate for periodontal defect regeneration but suffer from tedious procedures and low yields. Herein, we developed a facile yet scalable approach to prepare polylactide composite microspheres with outstanding drug-loading capability. It was realized by blending equimolar polylactide enantiomers at the temperature between the melting point of homocrystallites and stereocomplex (sc) crystallites, enabling the precipitation of sc crystallites in the form of microspheres. Meanwhile, epigallocatechin gallate (EGCG) and nano-hydroxyapatite were encapsulated in the microspheres in the designated amount. Such an assembly allowed the fast and sustained release of EGCG and Ca2+ ions. The resultant hybrid composite microspheres not only exhibited strong antimicrobial activity against typical oral pathogens (Porphyromonas gingivalis and Enterococcus faecalis), but also directly promoted osteogenic differentiation of periodontal ligament stem cells with good cytocompatibility. These dual-functional composite microspheres offer a desired drug delivery platform to address the practical needs for periodontitis treatment.


Discovery and Biosynthesis of Azabicyclene, a Conserved Nonribosomal Peptide in Pseudomonas aeruginosa.
Azabicyclene, an azetidine-containing natural product, was identified using quorum-sensing molecules to upregulate expression of a gene cluster highly conserved in the human pathogen Pseudomonas aeruginosa. Mutational studies of the gene cluster revealed essential genes for biosynthesis, including an unusual nonribosomal peptide synthetase. Reconstitution of this enzyme in vitro identified key biosynthetic intermediates. This work demonstrates a useful strategy for discovering quorum-sensing-regulated natural products. It sets the stage for understanding the biosynthesis and bioactivity of azabicyclene.


Chiari malformation: CSF flow dynamics in the craniocervical junction and syrinx.
A CSF flow study in patients with Chiari malformation (ChM) who undergo craniocervical junction decompression (CCJD). Using spatial modulation of magnetization (SPAMM), cerebrospinal fluid (CSF) flow velocities were measured at the prepontine (PP), anterior cervical (AC), and posterior cervical (PC) subarachnoid spaces (SAS) in healthy subjects (n = 11) and patients with Chiari malformation (ChM) before and/or after CCJD (n = 15). In the syringes, the intrasyrigeal pulsatile CSF motion was estimated qualitatively as present or absent. In normal subjects, the mean CSF velocities were 2.4 +/- 0.2 cm/s (PP), 2.8 +/- 0.3 cm/s (AC), and 2.4 +/- 0.2 cm/s (PC). Velocities were significantly lower than normal in patients with ChM prior to CCJD, reduced by 38%, 25%, and 79% in the 3 regions, respectively (P<0.001). Post-CCJD, velocities were 20% (PP), 100% (AC), and 40% (PC) greater than preoperatively (P<0.001). In ChM, the posterior cervical CSF flow velocity was low, increased minimally after CCJD and, by itself, had limited predictive value. Post-CCJD, an increase of the sum of anterior and posterior cervical CSF flow velocities by more than 20% consistently preceded or coincided with marked headache improvement. After CCJD, the finding that the intrasyringeal CSF pulsatile motion had become absent was an earlier and more sensitive predictor of motor or sensory improvement than a reduction in syrinx's size. SPAMM can be used to assess whether CCJD has restored CSF flow, predict outcome and provide pathophysiological insights in ChM and syringomyelia.


In vitro antibacterial activity of ceftazidime, unlike ciprofloxacin, improves in the presence of ZnO nanofluids under acidic conditions.
The development of antibiotic resistance among hospital pathogens has provided a great need for new antimicrobial agents. Zinc oxide nanoparticles (ZnO NPs) in combination with various antibiotics can act as a reducing agent for antibiotic resistance. The aim of this study was to investigate the influence and the mechanism of ZnO NPs on the antimicrobial activity of ciprofloxacin (CP) and ceftazidime (CAZ) against Enterococcus faecalis (E. faecalis) and Acinetobacter baumannii (A. baumannii) bacteria in acidic conditions (pH 5.5). ZnO NPs were synthesised using the solvothermal method and characterised. The MIC90 value of ZnO NPs against A. baumannii was 0.25 mg ml-1 and its highest growth-inhibitory activity was observed at 0.125 mg ml-1 for E. faecalis. The Fourier transform infrared spectroscopy spectra of ZnO NPs treated with antibiotics showed the interaction between ZnO NPs and each of the two antibiotics. ZnO NPs at a sub-inhibitory concentration had no effect on the antibacterial activity of CP and CAZ against E. faecalis and CP against A. baumannii. The action mechanism of ZnO NPs for enhancing the antibacterial efficacy of CAZ against A. baumannii was evaluated. ZnO NPs caused to increase in the antibacterial activity of CAZ against A. baumannii, possibly through the release of Zn2+ and increasing of membrane permeability.


Short-latency somatosensory evoked potentials in dystrophia myotonica.
Somatosensory evoked potentials (SEPs) were recorded in a group of 21 patients with dystrophia myotonica and in a group of controls. Those with dystrophia myotonica had longer absolute peak latencies due to slower peripheral conduction. SEP abnormalities revealed peripheral and/or central conduction delays in 33% of the dystrophia myotonica subjects. There was no apparent relationship between the clinical severity of the disease and SEP abnormality.


Uteroplacental insufficiency leads to hypertension, but not glucose intolerance or impaired skeletal muscle mitochondrial biogenesis, in 12-month-old rats.
Growth restriction impacts on offspring development and increases their risk of disease in adulthood which is exacerbated with "second hits." The aim of this study was to investigate if blood pressure, glucose tolerance, and skeletal muscle mitochondrial biogenesis were altered in 12-month-old male and female offspring with prenatal or postnatal growth restriction. Bilateral uterine vessel ligation induced uteroplacental insufficiency and growth restriction in offspring (Restricted). A sham surgery was also performed during pregnancy (Control) and some litters from sham mothers had their litter size reduced (Reduced litter), which restricted postnatal growth. Growth-restricted females only developed hypertension at 12 months, which was not observed in males. In Restricted females only homeostasis model assessment for insulin resistance was decreased, indicating enhanced hepatic insulin sensitivity, which was not observed in males. Plasma leptin was increased only in the Reduced males at 12 months compared to Control and Restricted males, which was not observed in females. Compared to Controls, leptin, ghrelin, and adiponectin were unaltered in the Restricted males and females, suggesting that at 12 months of age the reduction in body weight in the Restricted offspring is not a consequence of circulating adipokines. Skeletal muscle PGC-1α levels were unaltered in 12-month-old male and female rats, which indicate improvements in lean muscle mass by 12 months of age. In summary, sex strongly impacts the cardiometabolic effects of growth restriction in 12-month-old rats and it is females who are at particular risk of developing long-term hypertension following growth restriction.


Electroacupuncture Pretreatment Ameliorates Anesthesia and Surgery-Induced Cognitive Dysfunction via Activation of an α7-nAChR Signal in Aged Rats.
Postoperative cognitive dysfunction (POCD) after anesthesia and surgery (AS) is a common complication in the elderly population. A cholinergic-dependent signal, the alpha7-nicotinic acetylcholine receptor (α7-nAChR), has been suggested to regulate cognitive processes in a variety of neurologic diseases. In the current study, we determined whether electroacupuncture (EA) pretreatment ameliorates AS-induced POCD in aged rats, as well as the underlying mechanism. Male Sprague-Dawley rats (20 months old) were randomly assigned to the following 5 groups (n=12): vehicle; POCD (tibial fracture surgery); EA plus POCD; EA plus POCD and alpha-bungarotoxin (α-BGT); and POCD plus α-BGT groups. Alpha-bungarotoxin (1 μg/kg), a selective antagonist of α7-nAChR, was administrated via intraperitoneal injection before EA. Thirty days post-AS, the Morris water maze and a novel objective recognition test were used to evaluate cognitive function. Neuronal amount, apoptosis, microglial activation, percentage of high mobility group box 1 (HMGB1)- and nuclear factor-κB (NF-κB)-positive microglia, and levels of HMGB-1 downstream factors, including NF-κB, interleukin-6 (IL-6), and IL-1β, were detected by Nissl staining, immunofluorescence, and Western blot assays. EA pretreatment significantly increased crossing platform times and elevated the time with a novel object, restored the quantity of neurons, decreased TUNEL-positive neurons, alleviated activation of microglia, downregulated expression of HMGB1 and NF-κB in the microglia, and reduced levels of phosphor-NF-κB, IL-6, and IL-1β 35 days after AS, while α-BGT partially reversed these changes. EA pretreatment improved AS-induced POCD in aged rats, and the underlying mechanism may be associated with inhibition of HMGB1-NF-κB via an α7-nAChR signal in the microglia.


Management and Survival Patterns of Patients with Gliomatosis Cerebri: A SEER-Based Analysis.
We used the SEER (Surveillance Epidemiology and End Results) database (1999-2010) to analyze the clinical practice patterns and overall survival in patients with gliomatosis cerebri (GC), or glioma involving 3 or more lobes of the cerebrum. We identified 111 patients (age ≥18 years) with clinically or microscopically diagnosed GC in the SEER database. Analyses were performed to determine clinical practice patterns for these patients and whether these practices were associated with survival. Fifty-eight percent of the 111 patients with GC received microscopic confirmation of their diagnosis. Of the remaining patients, 40% were diagnosed via imaging or laboratory tests, and 2% had unknown methods of diagnosis. Seven percent of patients who did not have microscopic confirmation of their diagnosis received radiation therapy. Radiation therapy and surgery were not associated with survival. The only variable significantly associated with overall survival was age at diagnosis. Patients aged 18-50 years showed improved survival relative to patients aged >50 years (median survival, 11 and 6 months, respectively; P = 0.03). For patients aged >50 years, improved overall survival was observed in the post-temozolomide era (2005-2010) relative to those treated in the pre-temozolomide era (1999-2004) (median survival, 9 and 4 months, respectively; P = 0.005). In the SEER database, ∼40% of the patients with glioma with imaging findings of GC do not receive microscopic confirmation of their diagnosis. We propose that tissue confirmation is warranted in patients with GC, because genomic analysis of these specimens may provide insights that will contribute to meaningful therapeutic intervention.


Reformatting palivizumab and motavizumab from IgG to human IgA impairs their efficacy against RSV infection in vitro and in vivo.
Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization and mortality in young children. Protective therapy options are limited. Currently, palivizumab, a monoclonal IgG1 antibody, is the only licensed drug for RSV prophylaxis, although other IgG antibody candidates are being evaluated. However, at the respiratory mucosa, IgA antibodies are most abundant and act as the first line of defense against invading pathogens. Therefore, it would be logical to explore the potential of recombinant human IgA antibodies to protect against viral respiratory infection, but very little research on the topic has been published. Moreover, it is unknown whether human antibodies of the IgA isotype are better suited than those of the IgG isotype as antiviral drugs to combat respiratory infections. To address this, we generated various human IgA antibody formats of palivizumab and motavizumab, two well-characterized human IgG1 anti-RSV antibodies. We evaluated their efficacy to prevent RSV infection in vitro and in vivo and found similar, but somewhat decreased efficacy for different IgA subclasses and formats. Thus, reformatting palivizumab or motavizumab into IgA reduces the antiviral potency of either antibody. Moreover, our results indicate that the efficacy of intranasal IgA prophylaxis against RSV infection in human FcαRI transgenic mice is independent of Fc receptor expression.


Hypermetabolic mesenteric brown adipose tissue on dual-time point FDG PET/CT in a patient with benign retroperitoneal pheochromocytoma.
Intense FDG uptake of the mesenteric brown adipose tissue (BAT) is rare. We present a case of benign retroperitoneal pheochromocytoma showing multiple hypermetabolic regions corresponding with common locations of BAT. Furthermore, the mesenteric region showed intense FDG uptake, with SUVmax of 10.6. FDG PET/CT findings of this case supports the previous theories that the incidence of BAT may be higher in patients with pheochromocytoma than in patients without, and the intra-abdominal fat of human adults, including the omental fat, which is brown adipose tissue in infancy, becomes reactivated in the presence of high circulating noradrenaline concentrations.


Information and communication technology: students' health education in 1st- to 6th-grade South Korea elementary schools.
The purposes of this study were to (1) identify school nurses' awareness of information and communication technology (ICT) use in students' health education and (2) explore the barriers or reasons for the adoption of ICT in school nursing practice, while (3) presenting strategies to speed ICT diffusion and dissemination into practice. For data collection, 209 primary school nurses in K province of Korea were selected and e-mailed the questionnaires. Collected data were analyzed as frequency, percentages, and chi-square tests. The major reasons to adopt ICT were increasing school nurses' confidence in providing health education and improving teaching methods using diverse multimedia. The major barriers to utilization of ICT were lack of time for preparation of educational materials, lack of software availability, and lack of computer skills of school nurses and students. Several strategies were suggested to speed the diffusion of ICT into students' health education, such as integrating a health education course into regular curriculum. It is important to identify barriers and reasons for adoption of ICT in school nursing. In addition, strategies should be emphasized that result in more rapid diffusion of these technologies in school nursing practice.


Multifaceted role of insulin-like growth factors and mammalian target of rapamycin in skeletal muscle.
This review describes the current literature on the interaction between insulin-like growth factors, endocrine hormones, and branched-chain amino acids on muscle physiology in healthy young individuals and during select pathologic conditions. Emphasis is placed on the mechanism by which physical and hormonal signals are transduced at the cellular level to either grow or atrophy skeletal muscle. The key role of the mammalian target of rapamycin and its ability to respond to hypertrophic and atrophic signals informs our understanding how a combination of physical, nutritional, and pharmacologic therapies may be used in tandem to prevent or ameliorate reductions in muscle mass.


The fate of thymocytes labeled in vivo with CFSE.
The fate of thymic emigrants had so far been studied using a variety of markers, each of which had inherent limitations as to stability, toxicity, or selectivity. We describe a new technique which relies on the in vivo injection of CFSE, an esterified vital dye hitherto used at 80 times lower concentrations for in vitro cell labeling. We show that CFSE labels a representative sample of all thymocyte subsets and that these migrate at a rate of approximately 2-3 x 10(6) cells/day to peripheral lymphoid organs. We show that they enter lymph nodes at day 1 postinjection and stay for at least 21 days, whereas the turnover in the spleen is more rapid. We also show by immunohistochemistry, using peroxidase-labeled anti-FITC antibodies, that CFSE-labeled thymic emigrants are confined to T-dependent areas of peripheral lymphoid organs.


Galactosyl and N-acetylgalactosaminyl homeostasis: a function for mammalian asialoglycoprotein receptors.
Mammalian livers express endocytic cell surface receptors that specifically bind natural or synthetic molecules containing terminal galactosyl or N-acetylgalactosaminyl sugars. One of these hepatocyte receptors is the asialoglycoprotein receptor, which mediates the endocytosis and subsequent lysosomal degradation of these glyco-molecules. Although the receptor was discovered almost 30 years ago, the physiological reason why mammals have this receptor is still unknown. At the cellular level, the basic molecular function of the receptor is to mediate the uptake and ultimate degradation of galactosyl/N-acetylgalactosaminyl-containing molecules (ligands). At the organism level, however, the physiological function is uncertain. The identity of the natural ligands and the reasons for this elaborate receptor system to remove these ligands are both unknown. This article proposes an explanation for the purpose of this asialoglycoprotein receptor and its role in regulating the dynamic flux of galactosyl/N-acetylgalactosaminyl glycoconjugates in mammals.


Worsening COVID-19 Disease Course After Surgical Trauma: A Case Series.
Current guidelines from the American Society of Anesthesiologists recommend postponing elective surgery on COVID-19-positive patients for a minimum of four to twelve weeks. However, literature focusing on the outcomes of COVID-19-positive patients undergoing surgery is scarce. In this case series, the outcome of asymptomatic COVID-19 patients undergoing acute or semi-urgent surgery was evaluated. A case series of four patients between 32 and 82 years old with a confirmed SARS-CoV-2 infection undergoing acute or semi-urgent surgery was presented here. All four patients were asymptomatic for COVID-19, developing severe respiratory failure following endo CABG, caesarian section, a thyroidectomy, or abdominal surgery. ICU admission, together with invasive ventilation, was necessary for all patients. Two patients required venovenous extracorporeal membrane oxygenation treatment. A mortality of 50% was observed. In conclusion, the present case series suggests that elective surgery in asymptomatic SARS-CoV-2 infected patients might elicit an exacerbated COVID-19 disease course. This study endorses the current international guidelines recommending postponing elective surgery for SARS-CoV-2-positive patients for seven weeks, depending on the severity of the surgery and perioperative morbidities, to minimize postoperative mortality.


Contribution of neuroinflammation to changes in [11C]flumazenil binding in the rat brain: Evaluation of the inflamed pons as reference tissue.
[11C]Flumazenil is a well-known PET tracer for GABAA receptors and is mainly used as an imaging biomarker for neuronal loss. Recently, GABAA receptors on immune cells have been investigated as target for modulation of inflammation. Since neuronal loss is often accompanied by neuroinflammation, PET imaging with [11C]flumazenil is potentially affected by infiltrating immune cells. This may also compromise the validity of using the pons as reference tissue in quantitative pharmacokinetic analysis. This study aims to evaluate whether inflammatory processes in the brain can influence [11C]flumazenil uptake and affect the outcome of pharmacokinetic modeling when the pons is used as reference tissue. The herpes simplex encephalitis (HSE) rat model is known to cause neuroinflammation in the brainstem. Dynamic [11C]flumazenil PET scans of 60-min, accompanied by arterial blood sampling and metabolite analysis, were acquired at day 6-7days post-infection of male Wistar rats (HSE, n=5 and control, n=6). Additionally, the GABAA receptor was saturated by injection of unlabeled flumazenil prior to the tracer injection in 4 rats per group. PET data were analyzed by pharmacokinetic modeling. No statistically significant differences were found in the volume of distribution (VT) or non-displaceable binding potential (BPND) between control and HSE rats in any of the brain regions. Pre-saturation with unlabeled flumazenil resulted in a statistically significant reduction in [11C]flumazenil VT in all brain regions. The BPND obtained from SRTM exhibited a good correlation to DVR - 1 values from the two-tissue compartment model, coupled with some level of underestimation. Reliable quantification of [11C]flumazenil binding in rats can be obtained by pharmacokinetic analysis using the pons as a pseudo-reference tissue even in the presence of strong acute neuroinflammation.


An investigation of fluoride protection against dietary induced osteoporosis in the rat.
The purpose of this study was to determine whether the accumulation of substantial levels of fluoride in the skeleton during bone formation would significantly reduce, or prevent, the occurrence of osteoporosis experimentally induced at a later time with a low mineral-containing diet. Male weanling rats were pretreated for 15 weeks with either 0 or 50 ppm F in their drinking water, followed by treatment for four to twelve weeks with diets either optimal or deficient in both Ca and P. Intake of the Ca and P deficient diet resulted in a progressive loss of bone mass (per unit volume of femur), with little effect on the remaining bone. High skeletal F offered no protective effect. Ca and P depletion caused a significant decrease in bone breaking strength but produced only slight reduction in percentage ash in bone. Fluoride offered little protection against either. Neither skeletal F nor dietary Ca and P levels influenced the concentration of Ca, P or Ca/P ratios in bone ash. Skeletal Mg levels were slightly lower in the Ca and P depleted rats; however, F treatment essentially eliminated this. Ca and P depletion resulted in higher F levels in both incisors and bone. We conclude that osteoporosis was produced by feeding the Ca and P deficient diet. High skeletal F did not prevent nor reduce the severity of this dietary-induced osteoporosis.


A Sound Therapy-Based Intervention to Expand the Auditory Dynamic Range for Loudness among Persons with Sensorineural Hearing Losses: Case Evidence Showcasing Treatment Efficacy.
Case evidence is presented that highlights the clinical relevance and significance of a novel sound therapy-based treatment. This intervention has been shown to be efficacious in a randomized controlled trial for promoting expansion of the dynamic range for loudness and increased sound tolerance among persons with sensorineural hearing losses. Prior to treatment, these individuals were unable to use aided sound effectively because of their limited dynamic ranges. These promising treatment effects are shown in this article to be functionally significant, giving rise to improved speech understanding and enhanced hearing aid benefit and satisfaction, and, in turn, to enhanced quality of life posttreatment. These posttreatment sound therapy effects also are shown to be sustained, in whole or part, with aided environmental sound and to be dependent on specialized counseling to maximize treatment benefit. Importantly, the treatment appears to be efficacious for hearing-impaired persons with primary hyperacusis (i.e., abnormally reduced loudness discomfort levels [LDLs]) and for persons with loudness recruitment (i.e., LDLs within the typical range), which suggests the intervention should generalize across most individuals with reduced dynamic ranges owing to sensorineural hearing loss. An exception presented in this article is for a person describing the perceptual experience of pronounced loudness adaptation, which apparently rendered the sound therapy inaudible and ineffectual for this individual. Ultimately, these case examples showcase the enormous potential of a surprisingly simple sound therapy intervention, which has utility for virtually all audiologists to master and empower the adaptive plasticity of the auditory system to achieve remarkable treatment benefits for large numbers of individuals with sensorineural hearing losses.


The social worker in the emerging field of home care: Professional activities and ethical concerns.
Although home care is one of the fastest growing segments of the health care delivery system, there is little empirical data on the professional functions or ethical concerns of social workers employed in home care. To provide this information 118 social workers in proprietary and nonprofit agencies in one midwestern and one southern state were surveyed. The results indicated that social workers performed a wider array of professional functions with a more diverse population of patients than had been documented previously. Workers experienced ethical concerns related to self-determination, barriers to access of services, implementing advance directives, and assessment of mental competence most often. Workers in proprietary agencies rated the ethical concern of barriers to access of services as occurring significantly more often than workers in nonprofit agencies.


Prosthetic joint infection development of an evidence-based diagnostic algorithm.
Increasing rates of prosthetic joint infection (PJI) have presented challenges for general practitioners, orthopedic surgeons and the health care system in the recent years. The diagnosis of PJI is complex; multiple diagnostic tools are used in the attempt to correctly diagnose PJI. Evidence-based algorithms can help to identify PJI using standardized diagnostic steps. We reviewed relevant publications between 1990 and 2015 using a systematic literature search in MEDLINE and PUBMED. The selected search results were then classified into levels of evidence. The keywords were prosthetic joint infection, biofilm, diagnosis, sonication, antibiotic treatment, implant-associated infection, Staph. aureus, rifampicin, implant retention, pcr, maldi-tof, serology, synovial fluid, c-reactive protein level, total hip arthroplasty (THA), total knee arthroplasty (TKA) and combinations of these terms. From an initial 768 publications, 156 publications were stringently reviewed. Publications with class I-III recommendations (EAST) were considered. We developed an algorithm for the diagnostic approach to display the complex diagnosis of PJI in a clear and logically structured process according to ISO 5807. The evidence-based standardized algorithm combines modern clinical requirements and evidence-based treatment principles. The algorithm provides a detailed transparent standard operating procedure (SOP) for diagnosing PJI. Thus, consistently high, examiner-independent process quality is assured to meet the demands of modern quality management in PJI diagnosis.


Correlations between community size and student perceptions of value.
The purpose of this study was to determine if medical students' feeling of being valued was correlated to community size. The study, conducted in several communities in South Dakota, examined students' feeling of value relating to attending physicians, healthcare teams and patients. Student value items were added to student satisfaction surveys sent out to students at the end of their primary clinical year and data collected from two graduating classes of students (n=114). Student responses were grouped by clinical campus and mean responses by community size were calculated. Additionally, student encounter logs were reviewed for study participants to gauge participation levels during clinical encounters. The degree to which students felt valued by their physician attending, the healthcare team and the patients decreased consistently as community size increased. Differences were statistically significant between students in the smallest and largest communities. Additionally, students in the community of 15 000 felt significantly more valued than students in the community of 170 000. Furthermore, there also appears to be a relationship between the percentage of participation in patient care by students and community size. Students in the smaller, rural communities participated at a higher percentage rather than observing. There appears to be a relationship between community size and the extent to which students feel value. The degree to which students felt valued decreased consistently as community size increased. Differences were statistically significant between students in the smallest communities and the two largest communities. Students in the smaller, rural communities participated at a higher percentage. Additional studies are needed to address whether students participate more as a result of feeling valued, or whether participation leads to an enhanced perception of value by students.


[Technical specifications for hospital-based intensive monitoring of post-marketing Chinese patent medicine].
In 2013,China pharmaceutical regulatory department issued guiduance on postmarketing drug safety monitoring for industry. It aimed to encourage industry to carry out postmarketing drug safety monitoring including hospital-based intensive monitoring of postmarketing Chinese patent medicine. Subsequently,more and more such kind of studies have been performed all over China. However,in view of the current situation in this field,the development of hospital-based intensive monitoring of postmarketing Chinese patent medicine lacks standardization,such as unreasonable design,omission of reports about adverse drug reactions,inadequate process of quality control,non-standardized interpretation of adverse reactions,etc. Therefore,it is necessary to formulate relevant technical specifications to guide this area. The developing of this technical specification refered to the international post-marketing safety monitoring model and advanced design concepts and methods. We developed it under the guidance of relevant laws,regulations and technical documents in China. Meanwhile the characteristics of Chinese patent medicines and the real situation in this area were considered. The aim of this technical specification is to obtain the incidence,type,degree and clinical manifestation of adverse drug reactions of Chinese patent medicines,to find new risk signals of adverse reactions,to identify risk factors,and to provide a basis for the formulation of risk management and control plans. This specification has been approved by China association of Chinese medicine which is numbered T/CACM011-2016.


Paradoxical Shock and Management of a Post-percutaneous Mechanical Thrombectomy Device in a Morbidly Obese Patient With a Submassive Pulmonary Embolism.
A submassive pulmonary embolism (PE) is a type of PE where the pulmonary artery is partially obstructed. It is categorized as an intermediate risk when compared to massive PE, which presents as a complete obstruction of the pulmonary artery, therefore placing it in the high-risk category. In either case, if not promptly assessed and treated, it can prove to be fatal. We report the case of a morbidly obese middle-aged female who presented with a submassive PE. Based on the evaluation of the patient's pre-existing conditions, risk factors, clinical severity, imaging, and lab findings, it was concluded that percutaneous mechanical thrombectomy (PMT) was essential to promptly alleviate the clot burden. Following the procedure, it was observed that the patient became hemodynamically unstable, accompanied by hypoxemia and respiratory acidosis. With the assistance of pressors and later the placement of a right ventricular Impella device, the patient was successfully stabilized and, several days later, discharged from the hospital. This report explores the potential factors that may have contributed to the patient's hemodynamic instability and acute right ventricular failure after the PMT procedure. These factors can be attributed to pre-existing changes in the right ventricle (RV) as a result of morbid obesity, as well as possible associations with obstructive sleep apnea or obesity hypoventilation syndrome. Furthermore, it is important to highlight that patients exhibiting submassive PE can be considered suitable candidates for PMT, with careful consideration of the patient's medical history, clinical severity of symptoms, and diagnostic findings. It is worth noting that PMT intervention in this patient demonstrated a favorable outcome.


Lack of association of soluble CD40 ligand with the presence of acute myocardial infarction or ischemic stroke in the emergency department.
Soluble CD40 ligand (sCD40L) has been proposed as a new risk marker for cardiovascular diseases; however, its possible role as a diagnostic marker in the emergency department (ED) has not yet been investigated. We investigated sCD40L for the diagnosis of acute myocardial infarction or ischemic stroke in 1089 consecutive patients (525 males, 564 females; age, 17-98 years; median, 56 years) in an ED treating mainly adults with medical or neurologic emergencies. We used a research assay from Roche Diagnostics to measure sCD40L in heparinized plasma prepared from routinely drawn blood samples. Intraassay and interassay CVs in our laboratory ranged from 1.6%-4.2% and from 4.4%-4.9%, respectively. A multiple linear regression analysis revealed sCD40L concentration to be significantly associated with C-reactive protein concentration (P = 0.012) and platelet count (P < 0.001). In addition, a subgroup analysis revealed a significant association between smoking and sCD40L concentration (P = 0.006). All other tested variables, including discharge diagnosis, age, sex, and other laboratory variables, showed no significant associations. In adults presenting to the ED, sCD40L is not useful as a diagnostic marker for acute cardiac, cerebrovascular ischemic, or thromboembolic events.


Scaled down glass transition temperature in confined polymer nanofibers.
Arrays of polymer nanostructures have been widely used in many novel devices and nanofabrication methods. The glass transition temperature, which is a key parameter influencing the long-term stability of polymer nanostructures, has not yet been systematically studied and well understood. Here we study this technological and fundamental issue with polymers of different values of molar mass M confined in nanocylinders of a varying diameter D. The glass transition temperature Tg loses its dependence on the molar mass for D ≲ 100 nm, a range in which the relative depression of Tg varies as D(-0.44). For higher cylinder diameters, Tg progressively recovers its dependence on the molar mass. This is quantitatively reproduced by a model based on an equilibrium interfacial excess of free volume, which needs to be created unless provided by the chain ends. Our findings suggest that the structural perturbations during nanofabrication may strongly affect the long-term stability of arrays of polymer nanostructures.


Effects of posture on concentrations of serum proteins in healthy adults. Dependence on the molecular size of proteins.
The effect of posture on changes in protein composition of serum and its dependence on molecular size has been investigated in forty individuals classified by age and sex. Blood specimens were drawn (A) at 0700 hours with persons still resting in bed after an overnight sleep; (B) at 0815 hours, in sitting position after 1 h of moderate exercise and again (C) at 0915 hours, lying in bed after 1 h of recumbency. Concentrations of alpha 1-antitrypsin, albumin and alpha 2-macroglobulin in serum were determined with high analytical precision. The mean fractional increases of concentrations from lying (A) to sitting (B) were 0.069 for alpha 1-antitrypsin and 0.063 for albumin, but lower, 0.040, for alpha 2-macroglobulin. Thus these increases, being related to molecular size, were not simply caused by posture induced changes of plasma volume. Considering the results of each individual we found a constant difference between the increase of alpha 1-antitrypsin and alpha 2-macroglobulin of about 0.030 for the whole range of increases (i.e. for alpha 1-antitrypsin 0-0.15). In contrast, the effects of recumbency were independent of molecular size. The mean, fractional decreases in concentration induced by changing of position from sitting (B) to lying (C) were approximately 0.065 for all three proteins.


A peptide sequence of heparin/heparan sulfate (HP/HS)-interacting protein supports selective, high affinity binding of HP/HS and cell attachment.
We previously have identified a novel cell surface heparan sulfate/heparin (HS/HP)-interacting protein (HIP) found in human uterine epithelia and a variety of other human epithelial and endothelial cells and cell lines (Liu, S., Smith, S. E., Julian, J., Rohde, L. H., Karin, N. J., and Carson, D. D. (1996) J. Biol. Chem. 271, 11817-11823; Rohde, L. H., Julian, J., Babaknia, A., and Carson, D. D. (1996) J. Biol. Chem. 271, 11824-11830). The amino acid sequence predicted for HIP revealed a potential HS/HP-binding motif. In the present studies, a synthetic peptide corresponding to this putative HS/HP-binding motif, HIP peptide, was synthesized and examined with regard to its HS/HP binding and cell attachment promoting activity. Results using solid phase binding assays demonstrate that HIP peptide binds HS/HP with high selectivity and has high affinity for bulk HP (50% saturation congruent with 300 nM) and even higher affinity for a subset of polysaccharides found in commercial [3H]HP (half-saturation congruent with 10 nM). Moreover, HIP peptide binds subsets of cell and extracellular matrix-associated HS and dermatan sulfate expressed by RL95 cells, a human uterine adenocarcinoma cell line. HIP peptide also binds a similar fraction of HS as well as dermatan sulfate expressed by JAR cells, a human choriocarcinoma cell line. In contrast to binding of cell- or extracellular matrix-associated HS, HIP peptide does not bind secreted or released forms of HS or DS from either RL95 or JAR cells to a significant extent. HS species that bind to HIP peptide are generally larger, have a higher negative charge density, and have a larger proportion of di- and trisulfated disaccharide units than HS species that do not bind to HIP peptide, demonstrating structural differences among these polysaccharides. This same peptide supports HS-dependent JAR cell attachment. Collectively, these data demonstrate that a linear peptide sequence found within HIP can account, at least in part, for the HS/HP binding and cell adhesion promoting activities of this protein.


Toxicoses in livestock from the hemlocks (Conium and Cicuta spp.).
The hemlocks, Conium maculatum (poison-hemlock) and Cicuta spp. (waterhemlock), are poisonous plants that cause sizeable losss to the livestock industry. Clinical signs of poisonhemlock toxicosis are similar in all species of livestock and include muscular weakness, incordination, trembling, initial central nervous system stimulation, depression and death from respiratory paralysis. Poison-hemlock also causes skeletal defects in the offspring of cattle, pigs and sheep and cleft palate in pigs when ingested during specific periods of gestation. The primary toxicants in poison-hemlock are coniine and gamma-coniceine. Coniine predominates in mature plants and seed, whereas gamma-coniceine predominates in early growth of the plant. Waterhemlock is the most violently toxic poisonous plant known. The toxicant is cicutoxin, which acts on the central nervous system, causing violent convulsions and death. Clinical signs of poisoning appear within 15 min after ingestion of a lethal dose and include excessive salivation, nervousness, tremors, muscular weakness and convulsive seizures interspersed by intermittent periods of relaxation and a final paralytic seizure resulting in anoxia and death. Elevated activities of lactic dehydrogenase, aspartate aminotransferase and creatine kinase in blood are observed, indicative of muscular damage. Toxicoses from poisonhemlock and waterhemlock generally occur in early spring when both plants emerge before other, more palatable plants begin to grow. All parts of the poison-hemlock plant are toxic. The root or tubers of waterhemlock are toxic; however, experimental evidence concerning the toxicity of other plant parts is inconclusive.


Editorial: 150 Years of the Technische Universität München: Innovation since 1868.
"… On Easter Sunday 1868, the decree founding the Polytechnische Hochschule München (today's Technische Universität München; TUM) was signed by the 23-year-old Ludwig II, King of Bavaria. Entrepreneurial spirit has been a hallmark of the TUM from the start, and it was the first German university to have a branch abroad. Interdisciplinary research is key, not least in the Department of Chemistry …" Read more in the Guest Editorial by Wolfgang A. Herrmann.


Platycodin D inhibits migration, invasion, and growth of MDA-MB-231 human breast cancer cells via suppression of EGFR-mediated Akt and MAPK pathways.
Platycodin D (PD), an active triterpenoid saponin from Platycodon grandiflorum, has been known to inhibit the proliferation of a variety of cancer cells, but the effect of PD on the invasiveness of cancer cells is largely unknown. In this study, we first determined the molecular mechanism by which PD inhibits the migratory and invasive abilities of the highly metastatic MDA-MB-231 breast cancer cell line. We demonstrated that a non-cytotoxic concentration of PD markedly suppressed wound healing migration, invasion through the matrigel, and adhesion to an ECM-coated substrate in a dose-dependent manner. Moreover, PD inhibited cell invasion by reducing matrix metalloproteinase (MMP)-9 enzyme activity and mRNA expression. Western blot analysis indicated that PD potently suppressed the phosphorylation of extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK) as well as blocked the phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signaling pathway. Furthermore, PD treatment inhibited the DNA binding activity of NF-κB, which is known to mediate the expression of epidermal growth factor receptor (EGFR), as observed by electrophoretic mobility shift assay. Specific mechanisms of action exerted by PD involved the downregulation of EGFR and the inhibition of EGF-induced activation of the EGFR, MAPK, and PI3K/Akt pathways. The in vivo studies showed that PD significantly inhibited the growth of MDA-MB-231 xenograft tumors in BALB/c nude mice. These results suggest that PD might be a potential therapeutic candidate for the treatment of breast cancer metastasis.


Silver(I)-mediated base pairing in parallel-stranded DNA involving the luminescent cytosine analog 1,3-diaza-2-oxophenoxazine.
1,3-Diaza-2-oxophenoxazine (X) has been introduced as a ligand in silver(I)-mediated base pairing in a parallel DNA duplex. This fluorescent cytosine analog is capable of forming stabilizing X-Ag(I)-X and X-Ag(I)-C base pairs in DNA duplexes, as confirmed by temperature-dependent UV spectroscopy and luminescence spectroscopy. DFT calculations of the silver(I)-mediated base pairs suggest the presence of a synergistic hydrogen bond. Molecular dynamics (MD) simulations of entire DNA duplexes nicely underline the geometrical flexibility of these base pairs, with the synergistic hydrogen bond facing either the major or the minor groove. Upon silver(I) binding to the X:X or X:C base pairs, the luminescence emission maximum experiences a red shift from 448 to 460 nm upon excitation at 370 nm. Importantly, the luminescence of the 1,3-diaza-2-oxophenoxazine ligand is not quenched significantly upon binding a silver(I) ion. In fact, the luminescence intensity even increases upon formation of a X-Ag(I)-C base pair, which is expected to be beneficial for the development of biosensors. As a consequence, the silver(I)-mediated phenoxazinone base pairs represent the first strongly fluorescent metal-mediated base pairs.


NEAR-EARTH ASTEROID (152931) 2000 EA107: A PROBABLE BINARY.
CCD photometric observations of the near-Earth asteroid (152931) 2000 EA107 were made in 2019 March and April at the Center for Solar System Studies (CS3). Analysis of the data found that the asteroid is likely a binary. The primary period is P 1 = 4.1367 ± 0.0002 h with a lightcurve amplitude of A 1 = 0.29 ± 0.02 mag. The secondary period is P 2 = 16.079 ± 0.006 h with a lightcurve amplitude of A 2 = 0.16 ± 0.01 mag. No mutual events (occultations and/or eclipses) were seen to confirm the presence of a satellite.


NutriCatt protocol in the Enhanced Recovery After Surgery (ERAS) program for colorectal surgery: The nutritional support improves clinical and cost-effectiveness outcomes.
Postoperative complications and length of hospital stay (LOS) are major issues and affect hospital costs. Enhanced Recovery After Surgery (ERAS) protocols are effective in reducing morbidity and LOS after major surgery. We propose a nutritional protocol within ERAS programs in colorectal surgery, starting from preadmission. We compared the ERAS + NutriCatt approach versus the ERAS standard program adopted in our center in the previous months. Complications, LOS, hospital readmission at 30 days, and late complications (at 90 days) were assessed and compared. A cost-effectiveness analysis was performed. A total of 114 patients were treated according to the ERAS program between April 2015 and January 2016; 105 were enrolled in the ERAS + NutriCatt protocol from February to September 2016; Patients' characteristics were similar in the two groups, except for American Society of Anesthesiologists score, which was significantly worse in the ERAS + NutriCatt cohort; preoperative diagnoses and surgical approaches were similar in the two periods. LOS was significantly inferior in the ERAS + NutriCatt protocol (4.9 ± 1.7 d; 95% confidence interval [CI] 4.60-5.28) compared with the standard ERAS program (6.1 ± 3.9 d, 95% CI 5.36-6.81) (P = 0.006), as were postoperative complications (36, 34.3% versus 55, 48.2%; P = 0.03). Complications within 90 d were 0 in ERAS + NutriCatt and 4 in the ERAS standard cohort. Cost-effectiveness analyses indicated savings in the ERAS + NutriCatt protocol. Nutritional care, starting from the preadmission visit, is able to reduce LOS, postoperative and late complications, and costs, in addition to ERAS standard items in colorectal surgery.


Liver injury induced by dichloropropanols--changes in the time course on hematological and blood chemical examinations.
The toxicity of dichloropropanols (DCPs) was investigated by hematological and blood chemical examination. Solutions of two isomers of DCPs, 1,3-dichloro-2-propanol (DC2P) and 2,3-dichloro-1-propanol (DC1P) were dissolved in saline at a concentration of 100 mg/ml and 0.1 ml of each was subcutaneously injected into male Wistar rats weighing about 200 g. Acute changes on transaminases and number of platelets were determined in the time course. 6 hours later, transaminases showed significant increases while the number of platelets significantly decreased in the DC2P-treated group. In the half the of DC2P-treated group, transaminases had increased furthermore at 24 hours, while those in the rest were recovered to the control level. No changes were observed in the DC1P-treated group. These results indicate that there is a prominent hepatotoxicity in DC2P, with the individual diversities to some extent and the hepatic toxicity differs considerably between DC2P and DC1P. Therefore, the monitoring of the working environment and biological monitoring of DCPs should be mandatory, in the workplace where DCPs, especially DC2P, are utilized.


Gene therapy for vascular proliferative disorders.
Despite major advances in interventional techniques in recent years, restenosis remains an important late complication of percutaneous revascularization procedures. Vascular smooth muscle cell proliferation after arterial injury plays an important role in the pathogenesis of restenosis. Major progress has been made recently in elucidating the cellular and molecular mechanisms underlying this proliferative response. This in turn has led to the development of novel, gene-based approaches for the treatment and prevention of restenosis as well as other vascular proliferative disorders. Included among these are somatic gene therapy the ability to introduce and express recombinant genes in non-germ-line cells of a recipient organism in vivo. This article reviews specific genetic approaches that have recently been developed for the treatment of vascular proliferative disorders such as restenosis, focusing on the use of adenovirus-mediated arterial gene transfer strategies designed to suppress the vascular smooth muscle cell proliferative response associated with these diseases.


Three new orcinol-conjugated hydrolysable tannins from the leaves of Cleyera japonica.
Three new orcinol (3-hydroxy-5-methylphenol)-conjugated hydrolysable tannins, together with two known compounds were isolated from the leaves of Cleyera japonica (CJ), and have been tentatively named cleyeratannin A (1), cleyeratannin B (2) and cleyeratannin C (3). The chemical structures of these compounds were elucidated using 1 dimensional (1D)/2D NMR and high resolution FAB-MS, and the absolute configuration was confirmed by circular dichroism (CD). To evaluate their anti-oxidative activities, 1,1-diphenyl-2-picrylhydrazyl (DPPH)/free radical scavenging activity and nitroblue tetrazolium (NBT)/superoxide anion scavenging activity were determined.


Enhancing organic and inorganic carbon sequestration in calcareous soil by the combination of wheat straw and wood ash and/or lime.
Increasing organic carbon sequestration in agricultural soils is important for improving soil fertility and mitigating climate change. Wood ash is generally applied as a potassium fertilizer, but the effects of simultaneous incorporation of wood ash and crop straw on the turnover of soil organic carbon (SOC) and inorganic carbon (SIC) are not well understood. In this study, a 118-day lab incubation experiment was conducted using a calcareous soil (with 10 years of continuous maize cropping history) to study the effects of adding wheat straw, wood ash and lime. Our study showed that straw addition led to an increase in both SOC (19%) and SIC (3%). Wood ash and lime addition decreased CO2 emission by 182 and 1210 mg kg-1 and increased SIC by 125 and 1001 mg kg-1 during the incubation, respectively, which was due to supply of CaO from wood ash and lime. The increase of SOC content was 2.4% due to the addition of lime. In addition to straw addition enhanced straw-derived OC content, the addition of lime also increased straw-derived OC content by 34.5%. This study demonstrated that lime was more effective in reducing CO2 emission and and enhancing SOC than wood ash. In conclusion, adding lime to calcareous soil might be an effective method of enhancing carbon sequestration and slowing climate change.


Membrane properties for permeability testing: Skin versus synthetic membranes.
Synthetic membranes that are utilized in diffusion studies for topical and transdermal formulations are usually porous thin polymeric sheets for example cellulose acetate (CA) and polysulfones. In this study, the permeability of human skin was compared using two synthetic membranes: cellulose acetate and Strat-M® membrane and lipophilic and hydrophilic compounds either as saturated or formulated solutions as well as marketed dosage forms. Our data suggests that hydrophilic compounds have higher permeation in Strat-M membranes compared with lipophilic ones. High variation in permeability values, a typical property of biological membranes, was not observed with Strat-M. In addition, the permeability of Strat-M was closer to that of human skin than that of cellulose acetate (CA > Strat-M > Human skin). Our results suggest that Strat-M with little or no lot to lot variability can be applied in pilot studies of diffusion tests instead of human skin and is a better substitute than a cellulose acetate.


Science and intuition: do both have a place in clinical decision making?
Intuition is widely used in clinical decision making yet its use is underestimated compared to scientific decision-making methods. Information processing is used within scientific decision making and is methodical and analytical, whereas intuition relies more on a practitioner's perception. Intuition is an unconscious process and may be referred to as a 'sixth sense', 'hunch' or 'gut feeling'. It is not underpinned by valid and reliable measures. Expert health professionals use a rapid, automatic process to recognise familiar problems instantly. Intuition could therefore involve pattern recognition, where experts draw on experiences, so could be perceived as a cognitive skill rather than a perception or knowing without knowing how. The NHS places great importance on evidence-based practice but intuition is seemingly becoming an acceptable way of thinking and knowing in clinical decision making. Recognising nursing as an art allows intuition to be used and the environment or situation to be interpreted to help inform decision making. Intuition can be used in conjunction with evidence-based practice and to achieve good outcomes and deserves to be acknowledged within clinical practice.


Caveolin-1: a marker for pancreatic cancer diagnosis.
Pancreatic ductal adenocarcinoma is the fourth most common cause of cancer death, but the prognosis and management of patients have remained unchanged despite the progress in understanding the molecular basis of this disease. There is no specific/sensitive tumor marker for pancreatic cancer, thus the battle of searching for new and validated tumor markers has become a hot topic. Among various new markers, caveolin-1 - with its dual function in cancer - stands apart due to its relation to the development and progression stage of cancer. Caveolin-1 has been considered an independent unfavorable prognostic factor, its level being elevated and related to tumor size and histological grade. Our experimental data confirmed the link between tissue caveolin-1 and classical proliferation markers in pancreatic ductal adenocarcinoma, and its overexpression was validated by western blot and correlated with tumor aggressiveness. Although the studies on caveolin-1 and pancreatic cancer are only preliminary and reveal conflicting data, this review aims to signal that caveolin-1, as a versatile signaling molecule, may represent a valuable marker in this type of cancer. For caveolin-1 we can foresee two future directions of development: validation it as a biomarker and/or as an anticancer therapy target.


Designs of drug-combination phase I trials in oncology: a systematic review of the literature.
Combining several anticancer agents can increase the overall antitumor action, but at the same time, it can also increase the overall observed toxicity. Adaptive dose-escalation designs for drug combinations have recently emerged as an attractive alternative to algorithm-based designs, and they seem more effective in combination recommendations. These methods are not used in practice currently. Our aim is to describe international scientific practices in the setting of phase I drug combinations in oncology. A bibliometric study on phase I dose-finding combination trials was conducted using the Medline(®) PubMed database between 1 January, 2011, and 31 December 2013. Sorting by abstract, we selected all papers involving a minimum of two agents and then retained only those in which at least two agents were dose-escalated. Among the 847 references retrieved, 162 papers reported drug-combination phase I trials in which at least two agents were dose-escalated. In 88% of trials, a traditional or modified 3 + 3 dose-escalation design was used. All except one trial used a design developed for single-agent evaluation. Our study suggests that drug-combination phase I trials in oncology are very safe, as revealed by the calculated median dose-limiting toxicity rate of 6% at the recommended dose, which is far below the target rate in these trials (33%). We also examined requirements of phase I clinical trials in oncology with drug combinations and the potential advantages of novel approaches in early phases. Efforts to promote novel and innovative approaches among statisticians and clinicians appear valuable. Adaptive designs have an important role to play in early phase development.


[Receptors and markers: toward a science of imaging through hybridization].
Genomic- and proteomic-based imaging will enable the selection of populations and individuals "at risk"of suffering a certain disease before the clinical symptoms appear, identifying the existence, location, and extension of the bases of the disease, stratifying the risk, and making it possible to carry out and control treatments designed for each patient. In order to be efficacious, these molecular imaging techniques must generate both functional and structural information. The use of imaging probes together with advanced equipment allows numerous molecular complexes and cellular structures to be seen. Molecular imaging makes it possible to acquire, whether directly or indirectly, information about the spatial and temporal distribution of molecular or cellular processes that have not only clinical (diagnostic and therapeutic) applications but also basic (biochemical and physiological) applications. In the clinical area, nuclear medicine and radiology must work together to lead the development, implementation, and technological evaluation of molecular imaging. From this perspective, molecular hybridization techniques must progress toward the coordination of efforts, in training and in application as well as in research, to enable us to develop fully as imaging professionals in the service of healthcare. Molecular imaging provides imaging physicians with the possibility to advance substantially in early diagnosis, in the stratification of risk and prognosis, as well as in treatment monitoring in numerous biological and cellular processes related to the disease.


Effect of nimodipine on cerebral and organ blood flow in normal and posthypoxemic newborn piglets.
Using the isotope-labelled microsphere method, blood flow to the brain, the heart and the kidneys were studied in newborn piglets during nimodipine infusion. Twenty piglets were studied in two different groups. Group 1 (n = 8) was kept normoxic and given a continuous nimodipine infusion (15 micrograms/kg/min). Group 2 (n = 12) was made hypoxemic by breathing 10% O2 for 10 min followed by an identical nimodipine infusion as group 1. In spite of a significant systemic hypotension, nimodipine infusion alone significantly increased blood flow in the brain stem and right cardiac ventricle at 30-60 min of infusion, while blood flow to cerebellum, cerebrum and the left cardiac ventricle did not change. Blood flow to the kidneys decreased significantly. In posthypoxemic piglets nimodipine infusion gave almost similar flow patterns, however, the changes appeared at an earlier time. We conclude that in spite of a significant reduction in blood pressure, cerebral and cardiac blood flow is preserved both in normal and posthypoxemic animals even at high doses of nimodipine. However, because of the decreased blood flow to the kidneys further dose-response studies are needed before clinical use in asphyctic newborns.


Factors Associated With Contraceptive Method Choice and Initiation in Adolescents and Young Women.
The purpose of the study was to identify factors associated with uptake of contraceptive implants or intrauterine devices (IUDs) by adolescents and young women. For this prospective cohort study, we recruited English-speaking female contraceptive initiators aged 14-24 years attending a Title X-supported, youth-focused clinic. Immediately prior to their visits, participants completed surveys assessing demographic and reproductive characteristics and awareness of, interest in, and intent to initiate specific contraceptive methods. Participants also answered questions about their social contacts' contraceptive experiences. Following the visit, participants reported the method initiated and the perceived importance of provider counseling. We used a multivariable regression model to ascertain factors associated with initiation of an IUD, an implant, or a short-acting reversible method. We enrolled 1,048 contraceptive initiators: 277 initiated short-acting methods, 384 IUDs, and 387 implants. High previsit personal acceptability of the method was associated with choosing that method for both implants and IUDs. Knowing someone who uses a specific method and likes it was predictive of personal acceptability of that method (IUD adjusted odds ratio: 10.9, 95% confidence interval: 3.8-31.1; implant adjusted odds ratio: 7.0, 95% confidence interval: 2.3-21.0). However, 10.4% of those initiating IUDs and 14.2% of those initiating implants had never heard of the method before their appointment. Even women with previsit intent to initiate a specific method found importance in contraceptive counseling. Previsit personal acceptability, which was associated with social contacts' experiences, was the strongest predictor of specific method uptake in our study. However, counseling informed the decisions of those with low previsit awareness and supported patients with formed intent.


Transgene expression kinetics after transfection with cationic phosphonolipids in hematopoietic non adherent cells.
Cationic lipids are considered to be capable of efficiently and safely mediating DNA transfer into cells, although expression is transient. A new family of cationic lipids, called phosphonolipids, has been developed, with the relationship between the hydrophobic domain of the lipid molecules and the significant enhancement of transduction efficiency in a non-adherent cell line characterised in the present study. The kinetics of transfection efficiency were also investigated. Our results demonstrate that the peak of the transient expression of these reporter genes mediated by cationic lipids occurred within 3 to 14 days, depending on the aliphatic chain length of the complex used and on its formulation in the presence or absence of DOPE. Furthermore, the kinetics of transgene expression were found to differ in adherent and non-adherent cells. These results were obtained using three different techniques: CPRG, luminescence, and FACS-gal, and were in agreement with electron microscopy studies. We thus hypothesized that the plasma membrane composition of cells could affect the efficiency of transfection with cationic lipids. Our results suggest that phosphonolipids constitute a promising class of compounds for gene transfer protocols, and that galenic optimization should improve and modify the transfection efficiency of these DNA-lipid complexes.


LC-APCI-MS/MS Quantification and Topical Bioavailability of Chloroacetamide in Rats.
Chloroacetamide (CAA) is a preservative used in various cosmetic, personal care and household products. Due to the hazard potential for allergic reaction and reproductive toxicity, CAA is being considered a high priority for screening assessment and toxicological re-evaluation. This study describes the development of a highly specific and sensitive atmospheric pressure chemical ionization tandem mass spectrometry method for the determination of CAA in rat plasma and its application to a topical bioavailability study. Chromatographic separations were achieved on a C8 column using a highly aqueous mobile phase with a binary gradient elution. The assay was linear in the concentration range of 5-2,500 ng/mL (r ≥ 0.995) using a small sample volume (100 µL). Applicability of the assay was demonstrated in a bioavailability study in rats after i.v. injection (0.5 or 2 mg/kg) and topical application (7.02 mg/kg). Average elimination half-life and clearance ranged from 26.6 to 30.5 min and 53.9 to 57.3 mL/min/kg, respectively. Upon topical application, CAA was slowly but steadily absorbed for a prolonged time period (12 h). The topical bioavailability was 53.5 and 48.3% for emulsion and lotion, respectively. The developed assay may be useful to examine the relationship between exposure and toxic potential of CAA in risk assessment.


[The solitary thyroid nodule. Diagnostic and therapeutic problems].
The records of 93 patients who underwent surgery for solitary thyroid nodule were reviewed. It is emphasized no findings or diagnostic studies currently available which are sufficiently specific to differentiate benign from malignant lesions. All solitary nodules should be removed by excision of the involved thyroid lobe followed pathological examination: operative complications are rare.


The DNA sequence of argI from Escherichia coli K12.
The argI gene from E. coli K12 has been sequenced. It contains an open reading frame of 1002 bases which encodes a polypeptide of 334 amino acids. Three such polypeptides are required to form the functional catalytic trimer (c3) of ornithine transcarbamoylase (OTCase-1, EC 220.127.116.11). The molecular mass of the mature trimer deduced from the amino acid sequence is 114,465 daltons. An altered form of argI was produced when a 1.6 kilobase DdeI fragment was subcloned into the HincII site of plasmid pUC8 extending the open reading frame an additional 20 nucleotides. It has been previously reported that the amino-terminal region of the respective polypeptides of argI, argF, and pyrB of E. coli possessed significant homology. In contrast, the homologous promoter/operator regions of argI and argF did not appear to share any homologies with pyrB. However, a closer scrutiny of the nucleotide sequence immediately preceding the pyrBI attenuator revealed a remarkable similarity to the argI and argF control region.


Acute bilateral useless hand syndrome: a rare presenting manifestation of vitamin B12 deficiency.
We report a case of bilateral useless hand syndrome, a rare presenting manifestation of vitamin B12 deficiency. A 38-year-old man, a strict vegetarian and a teacher by occupation, presented with acute onset clumsiness of both hands while performing fine movements. Detailed history-taking, examination of the patient and relevant investigations (complete blood count, serum vitamin B12 and MRI of the cervical spinal cord) were carried out. Laboratory analysis was suggestive of vitamin B12 deficiency and MRI demonstrated a lesion involving the posterior columns of the cervical cord. The patient was diagnosed as a case of non-compressive cervical myelopathy predominantly involving the posterior column due to vitamin B12 deficiency. Acute bilateral useless hand syndrome can be a rare presenting feature of vitamin B12 deficiency.


[Cardioverter-defibrillator implantation and follow-up in a non-university hospital].
Implantable cardioverter-defibrillators (ICD) have emerged as a major treatment for life threatening ventricular arrhythmias. This technique is available in France in all the university hospitals and, with the favor of the new regulation, in some qualified private centers. However, ICD implantation and follow-up in a non-university hospital is infrequent. This study reports long-term results following ICD implantation in 152 patients (age 61+/-13 years). The vast majority (49%) of the patients were implanted for post-infarction ventricular tachycardia and 17% in primary prevention for left ventricular dysfunction. An appropriate therapy was delivered in 83 patients including 68 (81%) treated by antitachycardia pacing without the need for a cardioversion shock. An inappropriate shock was observed in 13 patients (9%). Because of iterative shocks, catheter radiofrequency ablation was proposed among 9 patients, with a success in 8. In conclusion, the technique of the implantable defibrillator can be performed in a non-university hospital with acceptable results. The increase in the ICD number in France implies that there is a need for collaboration between non-university and university hospitals in managing routine and emergency follow-up.


Possible relationship between histamine and nitric oxide release in the postischemic flow response following mesenteric ischemia of different durations.
During the postischemic flow response (PFR), vasodilator mediators such as nitric oxide (NO) and histamine are liberated, influencing the blood flow rate at the onset of reperfusion. The possible roles of these two mediators, and the relationship between their release, were examined during segmental intestinal ischemia of different durations and subsequent reperfusion in two series of anesthetized dogs. In series I (untreated ischemia), 15, 30, 60, and 120 min ischemia and 2 h reperfusion were studied. In series II, the same experimental protocol was repeated after pretreatment with the NO synthase inhibitor N-nitro-L-arginine (NNA, 10 mumol/kg, i.e., 2.19 mg/kg). Intramucosal pH (pHi), segmental blood flow and effluent histamine levels were measured, and segmental vascular resistance (SVR) and PFR volumes were calculated. The ischemic periods caused a considerable fall in pHi. Reperfusion resulted in an early return to normal pHi levels following a 15 or 30 min ischemia, but this process took longer after longer occlusions. In the later phase of reperfusion, SVR was elevated. The PFR volume increased in proportion to the duration of occlusion, except after the 120 min ischemia. At the onset of reperfusion, peak histamine levels rose in parallel with the duration of ischemia. During reperfusion, a prolonged decrease in pHi, an increase in SVR, and a reduction in PFR volume, with no significant histamine level elevation, were observed in the NNA-treated groups. This study indicates that both NO and histamine take part in the PFR in the canine small intestine. Inhibition of NO synthesis prevents the postischemic release of histamine.


Top-down and bottom-up forces interact at thermal range extremes on American lobster.
Exploited marine populations are thought to be regulated by the effects of fishing, species interactions and climate. Yet, it is unclear how these forces interact and vary across a species' range. We conducted a meta-analysis of American lobster (Homarus americanus) abundance data throughout the entirety of the species' range, testing competing hypotheses about bottom-up (climate, temperature) vs. top-down (predation, fishing) regulation along a strong thermal gradient. Our results suggest an interaction between predation and thermal range - predation effects dominated at the cold and warm extremes, but not at the centre of the species' range. Similarly, there was consistent support for a positive climate effect on lobster recruitment at warm range extremes. In contrast, fishing effort followed, rather than led changes in lobster abundance over time. Our analysis suggests that the relative effects of top-down and bottom-up forcing in regulating marine populations may intensify at thermal range boundaries and weaken at the core of a species' range.


Realizing potential: improving interdisciplinary professional/paraprofessional health care teams in Canada's northern aboriginal communities through education.
To address a shortage of health professional human resources and to overcome cultural barriers, the interdisciplinary health care teams practicing in most northern Canadian aboriginal communities include a number of paraprofessionals recruited locally. This model has great potential to fill service gaps in many rural contexts; there are challenges, however. Drawing from an extensive program of research in indigenous communities in the northwestern part of the Province of Ontario, we identify factors fundamental to effective team functioning: members' clarity about their own and others' roles, appreciation of their respective 'equal but different' knowledge bases, and confidence in one another's competence. We argue for an extension of the information on interdisciplinary practice included in health science education programs to address these issues, thereby enhancing the utility of paraprofessionals within the health human resource mix in rural areas.


Closed-form multiple source direction-of-arrival estimator under reverberant environments.
Accurate direction-of-arrival (DOA) estimation of multiple sources, simultaneously active in a reverberant environment, remains a challenge, as the multi-path acoustic reflections and overlapped periods dramatically distort the direct-path wave propagation. This article proposes a prominent solution localizing multiple sources in a reverberant environment using closed-form estimates, circumventing any exhaustive search over the two-dimensional directional space. Apart from a low complexity cost, the algorithm has robustness to reverberant, inactive, and overlapped periods and an ease of operation in practice, achieving sufficient accuracy compared to state-of-the-art approaches. Specifically, this algorithm localizes an unknown number of sources through four steps: (i) decomposing the frequency domain signals on a spherical array to the spherical harmonics domain; (ii) extracting the first-order relative harmonic coefficients as the input features; (iii) achieving direct-path dominance detection and localization using closed-form estimation; and (iv) estimating the number of sources and their DOAs based on those pass the direct-path detection. Experimental results, using extensive simulated and real-life recordings, confirm the algorithm with a significantly reduced computational complexity, while preserving competitive localization accuracy as compared to the baseline approaches. Additional tests confirm this low-complexity algorithm even with a potential capacity for online DOA tracking of multiple moving sources.


[Free oxygen radicals in patients with hypertension].
The objective of the investigation was to test the impact of hypertension on the formation of free oxygen radicals which participate in the development of atherosclerosis. Using the method of luminol-dependent chemiluminescence, the authors assessed the spontaneous and stimulated production of free oxygen radicals in phagocytic cells of complete blood in a group of healthy subjects, in not treated essential hypertension (EH), essential hypertension treated with metipranolol (Trimepranol Spofa) and EH treated with diltiazem (Blokalcin Lachema). A statistically significant increase of spontaneous and activated production of free oxygen radicals was found in the group of EH treated with diltiazem. Differences between the group of healthy subjects, untreated EH and hypertension treated with metipranolol were not statistically significant.


Dispersionless density functional theory.
A new density functional (DF) method is proposed for calculations of intermolecular interaction energies. The exchange-correlation functional was optimized in such a way that the method recovers the interaction energies with the dispersion (including exchange-dispersion) component subtracted and therefore our approach is named the dispersionless DF (dlDF) method. The dlDF method is shown to predict very well the dispersionless part of the interaction energy for all types of intermolecular interactions. Thus, if combined with a dispersion component, computed ab initio or from a simple function fitted to ab initio values, it provides accurate and physically justified interaction energies in the whole range of intermolecular separations. Our dispersion function is significantly more accurate than the published ones.


Geniposide Attenuates the Phosphorylation of Tau Protein in Cellular and Insulin-deficient APP/PS1 Transgenic Mouse Model of Alzheimer's Disease.
Our previous studies have shown that geniposide plays an essential role in glucose-stimulated insulin secretion from pancreatic β cells and also regulates the metabolism of Aβ and its deposition in neurons. In this study, we reported that insulin deficiency induced significant increase of tau phosphorylation. Administration of geniposide for 4 weeks significantly decreased the phosphorylated level of tau and the acceleration of GSK-3β phosphorylation in the brain of APP/PS1 transgenic mice induced by insulin deficiency. We also observed that geniposide decreased the phosphorylation of tau protein directly and increased the phosphorylation of Akt in primary cultured cortical neurons. Furthermore, geniposide enhanced the role of insulin on the phosphorylation of Akt, GSK-3β, and tau in primary cultured cortical neurons. And these effects of geniposide in cortical neurons could be prevented by preincubation with LY294002, an inhibitor of PI3K. Taken together, our findings provide a mechanistic and perhaps a foundational link between diabetes and Alzheimer's disease and are consistent with the notion that geniposide might play an essential role on the phosphorylation of tau protein via enhancing insulin signaling and may convey a therapeutic benefit in Alzheimer's disease.


Secretion of Bacillus amyloliquefaciens Transglutaminase from Lactococcus lactis and Its Enhancement of Food Gel Properties.
(1) Background: Microbial transglutaminases (MTGase) catalyze protein crosslink. This is useful in the food industry to improve gelation, water holding capacity, and emulsifying capacity during foodstuff manufacturing. The production of MTGase in wild-type strains renders low yield and high costs of downstream purification, limiting its industrial applications. (2) Methods: In this work, MTGase from Bacillus amyloliquefaciens BH072 (BaMTGase) has been heterologously expressed in Lactococcus lactis, using the signal peptide Usp45 to direct the secretion of recombinant BaMTGase out of the cell for easier purification. (3) Results: In these conditions, MTGase was purified with a high yield (48.7 ± 0.2 mg/L) and high enzyme activity (28.6 ± 0.5 U/mg). Next, BaMTGase was tested for industrial applications. Recombinant BaMTGase and commercial MTGase were used for SPI solution crosslinking. BaMTGase formed a harder gel with higher water-holding capacity and a dense and smooth gel microstructure. (4) Conclusions: This work provides an attractive food-grade cell factory for the food industry and offers a suitable chassis for MTGase production.


Symptom management in the elderly cancer patient: fatigue, pain, and depression.
Patients who are > or =65 years of age are the fastest growing segment of the U.S. population. These patients with already existing physiologic decline and comorbidities, when diagnosed with cancer, provide considerable challenges in management issues. Along with therapy for the tumor the practicing oncologist must also keep in mind the various symptoms, like fatigue, pain, and depression, that may occur due to the tumor itself or due to therapy. The prevalence of fatigue is greater than 50-70% in advanced cancer. The tools to measure fatigue are all subjective in nature and no one tool has been tested in the elderly cancer patient. Treatment of fatigue in the elderly may involve education, antidepressants, treatment of anemia, exercise, and use of psychostimulants. Pain is present is 80% of elderly patients with advanced cancer. Pain should be assessed in a systematic way and it has been shown that the Visual Descriptor Scale is the tool most preferred by the elderly. Several guidelines for management of pain exist and options include acetaminophen, nonsteroidal anti-inflammatory drugs, opioids, adjuvant analgesics, and education of patients and caregivers. Depression is also a prevalent symptom arising from a variety of causes. There are many validated tools to measure depression in the elderly like the Geriatric Depression Scale. Treatment includes use of education, selective serotonin reuptake inhibitors, psychotherapy, and electroconvulsive therapy. There exists an interplay of many of these symptoms and quite often they can occur simultaneously in the elderly cancer patient. Future research is needed to expand our base of knowledge on the occurrence and management of each of these symptoms and to better understand how aging systems interact with these phenomena to produce unique situations in older adults.


HLA class II allele and haplotype frequencies in Iranian patients with leukemia.
Previous studies demonstrated significant differences in a number of HLA allele frequencies in leukemia patients and normal subjects. In this study, we have analyzed HLA class II alleles and haplotypes in 110 leukemia patients (60 acute myelogenous leukemia "AML", 50 chronic myelogenous leukemia"CML") and 180 unrelated normal subjects. Blood samples were collected from all of the patients and control subjects. DNA was extracted by salting out method and HLA typing was performed using PCR-SSP method. Significant positive association with AML was obtained for HLA-DRB1*11allele (35% vs. 24.7%, P=0.033). Two alleles including HLA-DRB4 and -DQB1*0303 were significantly less frequent in AML patients than in controls. HLA-DQB1*0303 allele was never observed in CML patients compared with allele frequency in controls (4.2%). According to haplotype analysis, HLA-DRB1*0101/DQA1*0104/-DQB1*0501 frequencies were significantly higher and -DRB1*16/-DQA1*01021/-DQB1*0501 frequencies were significantly lower in CML patients than in controls. In conclusion it is suggested that HLA-DRB1*16 allele and HLA-DRB1*15/-DQA1*0103/-DQB1*06011 and -DRB1*16/-DQA1*01021/-DQB1*0501 haplotypes predispose individuals to AML and HLA-DRB4 allele predispose to CML. Future studies are needed to confirm these results and establish the role of these associations in AML and CML.


Relationship between tooth contacts in the retruded contact position and mandibular positioning during retrusion.
We conducted a series of studies with the purpose to investigate the locations of tooth contacts in the retruded contact position (RCP) and to discuss their significance in the stomatognathic system. In the present study, the relationship between the locations of RCP contacts and mandibular positioning during retrusion was examined. Thirty dentists and clinical residents were selected as subjects. One specialist in prosthetic dentistry examined each subject for the location of the RCP contacts. The mandibular positioning during retrusion was measured using a mandibular movement analysis system with six degrees of freedom. Originally programmed software was developed. Five reference points were selected: the central lower incisor (point I), the first molars on both sides (points RM and LM) and the condyles on both sides (points RC and LC). Tooth contact was observed most frequently at the second molar, followed by the first premolar. Points I, RM and LM all moved in an inferior-posterior direction, whereas points RC and LC moved in various directions ranging from superior-posterior to inferior-posterior. When the subjects were divided into two groups according to the most anterior tooth of occlusion in the RCP, the condylar positioning tended to be more superior in the group with molar contact than that with premolar contact. These results suggest that the locations of RCP contacts could be an important factor in jaw guidance during retrusion.


A minimal optical trapping and imaging microscopy system.
We report the construction and testing of a simple and versatile optical trapping apparatus, suitable for visualizing individual microtubules (∼25 nm in diameter) and performing single-molecule studies, using a minimal set of components. This design is based on a conventional, inverted microscope, operating under plain bright field illumination. A single laser beam enables standard optical trapping and the measurement of molecular displacements and forces, whereas digital image processing affords real-time sample visualization with reduced noise and enhanced contrast. We have tested our trapping and imaging instrument by measuring the persistence length of individual double-stranded DNA molecules, and by following the stepping of single kinesin motor proteins along clearly imaged microtubules. The approach presented here provides a straightforward alternative for studies of biomaterials and individual biomolecules.


Atypical fibroxanthoma of hand.
Atypical fibroxanthoma (AFX) is a rare cutaneous ulcerative lesion with a good prognosis. Diagnosis is difficult and is usually made by exclusion from pleomorphic dermal sarcoma and squamous cell carcinoma. Definitive treatment varies from Mohs micrographic surgery to wide local excision. We present a case of 76-year-old woman with AFX over the dorsum of her left hand. The tumour was excised and the resulting defect was reconstructed with a local second dorsal metacarpal artery perforator flap.


Hypochondroplasia, Acanthosis Nigricans, and Insulin Resistance in a Child with FGFR3 Mutation: Is It Just an Association?
FGFR3 mutations cause wide spectrum of disorders ranging from skeletal dysplasias (hypochondroplasia, achondroplasia, and thanatophoric dysplasia), benign skin tumors (epidermal nevi, seborrhaeic keratosis, and acanthosis nigricans), and epithelial malignancies (multiple myeloma and prostate and bladder carcinoma). Hypochondroplasia is the most common type of short-limb dwarfism in children resulting from fibroblast growth factor receptor 3 (FGFR3) mutation. Acanthosis nigricans might be seen in severe skeletal dysplasia, including thanatophoric dysplasia and SADDAN syndrome, without a biochemical evidence of hyperinsulinemia. Insulin insensitivity and acanthosis nigricans are uncommonly seen in hypochondroplasia patients with FGFR3 mutations which may represent a new association. We aim to describe the association of hypochondroplasia, acanthosis nigricans, and insulin resistance in a child harboring FGFR3 mutation. To our knowledge, this is the first case report associating the p.N540 with acanthosis nigricans and the second to describe hyperinsulinemia in hypochondroplasia. This finding demonstrates the possible coexistence of insulin insensitivity and acanthosis nigricans in hypochondroplasia patients.


Eccrine poromatosis in a patient with acute myeloid leukemia following chemotherapy.
Eccrine poromas are rare, benign adnexal tumors that often occur as solitary papules. Rarely, eccrine poromas can present as multiple lesions, which is referred to as eccrine poromatosis. We report a case of eccrine poromatosis occuring on the palms and soles occuring after chemotherapy in a patient with a history of acute myeloid leukemia.