Sex-Specific Mediation Effects of Workplace Bullying on Associations between Employees' Weight Status and Psychological Health Impairments.
Individuals with obesity face weight-related discrimination in many life domains, including workplace bullying, especially in female employees with obesity. However, associations between experiences of workplace bullying and psychological health impairments considering weight status and sex remain unclear. Within a representative population-based sample of N = 1290 employees, self-reported experiences of workplace bullying were examined for variations by weight status and sex. Using path analyses, sex-specific mediation effects of workplace bullying on associations between weight status and work-related psychological health impairments (burnout symptoms, quality of life) were tested. Employees with obesity experienced more workplace bullying than those with normal weight. Workplace bullying was positively associated with psychological health impairments and partially mediated the associations between higher weight status and elevated burnout symptoms and lower quality of life in women, but not in men. The result that more experiences of workplace bullying were, compared with weight status, more strongly associated with work-related psychological health impairments in women, but not in men, uniquely extends evidence on sex-specific effects within weight-related discrimination. Continued efforts by researchers, employers, and policy makers are needed to reduce weight-related discrimination in work settings, eventually increasing employees' health and job productivity.


Early Erythema Migrans: Do Not Count on Plasma Cells.
Three hundred thousand new cases of Lyme disease are diagnosed annually in the United States. The earliest manifestation of the disease, erythema migrans, occurs earlier than serologic conversion, and skin biopsies can be very helpful in suggesting the diagnosis. Histopathologic findings vary depending on where in the lesion the specimen is taken, but typically consist of a superficial and deep perivascular and interstitial lymphocytic infiltrate with eosinophils centrally and with histiocytes and plasma cells at the periphery. Rare cases with interstitial histiocytes and rare-to-sparse plasma cells exist. We present a 67-year-old man whose skin biopsy, taken on day 2 of his eruption, demonstrated a subtle perivascular and interstitial infiltrate of histiocytes without plasma cells. Dermatopathologists need to be aware of this pattern and consider the diagnosis of erythema migrans, despite negative initial serologic testing.


A comparative study of itraconazole in various dose schedules in the treatment of pulmonary aspergilloma in treated patients of pulmonary tuberculosis.
The optimal dose, duration, and efficacy of itraconazole in Indian patients of pulmonary aspergilloma (PA) are not clearly defined. Therefore, a study was carried out, to resolve these issues in diagnosed cases of PA complicating old treated patients of pulmonary tuberculosis. The study patients randomly received itraconazole either in a fixed dose schedule of 200 mg (group I), 200 mg twice daily (group II) or a variable dose schedule (group III), for 12 months. All the patients were followed up for the entire duration of the study for clinical, radiological, and immunological response. The side effects were recorded as and when reported by the patients and managed symptomatically. A total of 60 patients were enrolled, 20, in each group. There were no intergroup differences with regard to age, sex, body weight, smoking status, alcohol intake, symptoms, Potassium hydroxide (KOH) mount, fungal culture, pattern of radiological lesions or anti-aspergillus antibodies (anti-Asp-Ab) titers. The radiological response was poor in group I patients, as compared to the other groups, at two months (P < 0.05). The dose of itraconazole was increased in five of the patients in group I due to poor response. A higher number of group II patients suffered side effects and the dose of itraconazole had to be decreased in three of these patients, but none of the patients on a variable dose schedule required a change in dose schedule. Thus, a weight-based variable dose schedule of itraconazole was found to be a more effective and safer modality in the management of PA than a fixed dose schedule.


An improved method for the estimation and visualization of velocity fields from gastric high-resolution electrical mapping.
High-resolution (HR) electrical mapping is an important clinical research tool for understanding normal and abnormal gastric electrophysiology. Analyzing velocities of gastric electrical activity in a reliable and accurate manner can provide additional valuable information for quantitatively and qualitatively comparing features across and within subjects, particularly during gastric dysrhythmias. In this study, we compared three methods of estimating velocities from HR recordings to determine which method was the most reliable for use with gastric HR electrical mapping. The three methods were 1) simple finite difference (FD) 2) smoothed finite difference (FDSM), and 3) a polynomial-based method. With synthetic data, the accuracy of the simple FD method resulted in velocity errors almost twice that of the FDSM and the polynomial-based method, in the presence of activation time error up to 0.5 s. With three synthetic cases under various noise types and levels, the FDSM resulted in average speed error of 3.2% and an average angle error of 2.0° and the polynomial-based method had an average speed error of 3.3% and an average angle error of 1.7°. With experimental gastric slow wave recordings performed in pigs, the three methods estimated similar velocities (6.3-7.3 mm/s), but the FDSM method had a lower standard deviation in its velocity estimate than the simple FD and the polynomial-based method, leading it to be the method of choice for velocity estimation in gastric slow wave propagation. An improved method for visualizing velocity fields is also presented.


Procera AllCeram crowns followed for 5 to 10.5 years: a prospective clinical study.
This is a report on Procera AllCeram crowns in a prospective multicenter study. The aim of the study was to evaluate AllCeram crowns in dental practice over a 5- to 10.5-year period. Some of the AllCeram crowns were among the very first that were placed. The crowns were placed between 1989 and 1995. Twelve clinicians at nine clinics placed 87 crowns in 50 patients. The California Dental Association quality evaluation system was used for assessment of marginal integrity and esthetics. After 5 and 10 years a cumulative survival rate of 97.7% and 93.5%, respectively, and a cumulative success rate of 97.7% and 92.2%, respectively, was recorded. Six crowns (7%) were recorded as failures; five of these crowns (6%) had to be remade. The marginal integrity was considered excellent or acceptable for 92% of the crowns. Bleeding was somewhat more often recorded at teeth with AllCeram crowns (39%) than at contralateral teeth (27%). Endodontic treatment was performed for a low number (2%) of the AllCeram crowns. The patients found the esthetics to be excellent. The results of this study demonstrate about the same clinical outcome as has been reported by similar studies on all-ceramic crowns built on a core of alumina. The outcome is also in agreement with that reported for metal-ceramic crowns. The results indicate a good prognosis for Procera AllCeram crowns also for posterior teeth.


Control of hyperlipidaemia in juvenile diabetes. Standard and corn-oil diets compared over a period of 10 years.
The results of the first 10 years of a prospective study of the effect of corn-oil and standard diets given to diabetic children since diagnosis suggest that the corn-oil diets currently available in Britain are not acceptable to most diabetic children and adolescents. Attempts to administer such diets may result in hyperpre-beta-lipoproteinaemia. In most diabetic children normal serum lipid levels can be maintained with adequate diabetic control and a standard diabetic diet.


Ion Homeostasis in Chloroplasts under Salinity and Mineral Deficiency: II. Solute Distribution between Chloroplasts and Extrachloroplastic Space under Excess or Deficiency of Sulfate, Phosphate, or Magnesium.
Spinach (Spinacia oleracea var "Yates") plants grown hydroponically were exposed to an excess or deficiency of various mineral ions. Solutes were measured in leaf extracts and in isolated intact chloroplasts. Under phosphate (120 millimoles per liter NaH(2) PO(4)), sulfate (200 millimolar per liter (Na(2) SO(4)), or magnesium excess (150 millimolar per liter MgCl(2)), concentrations of these ions in leaf extracts increased, but in chloroplasts, concentrations of all ions remained constant. Concentrations of quarternary ammonium compounds in chloroplasts increased. Under mild phosphate or magnesium deficiency, concentrations of these ions decreased in chloroplasts less than in whole leaf extracts. Under severe sulfate deficiency causing chlorosis in younger leaves, sulfate concentrations in chloroplasts remained even unchanged, despite a drastic decrease of sulfate concentrations both in green and in chlorotic leaves. Together with results from a companion study (G Schröppel-Meier, WM Kaiser 1988 Plant Physiol 87: 822-827) our data demonstrate that leaf cells are able to keep the concentrations of several mineral ions rather constant in metabolically active compartments even at extremely large variations of ion concentrations in the culture solution and in the leaves.


Phase-space invariants for aggregates of particles: hyperangular momenta and partitions of the classical kinetic energy.
Rigorous definitions are presented for the kinematic angular momentum K of a system of classical particles (a concept dual to the conventional angular momentum J), the angular momentum L(xi) associated with the moments of inertia, and the contributions to the total kinetic energy of the system from various modes of the motion of the particles. Some key properties of these quantities are described-in particular, their invariance under any orthogonal coordinate transformation and the inequalities they are subject to. The main mathematical tool exploited is the singular value decomposition of rectangular matrices and its differentiation with respect to a parameter. The quantities introduced employ as ingredients particle coordinates and momenta, commonly available in classical trajectory studies of chemical reactions and in molecular dynamics simulations, and thus are of prospective use as sensitive and immediately calculated indicators of phase transitions, isomerizations, onsets of chaotic behavior, and other dynamical critical phenomena in classical microaggregates, such as nanoscale clusters.


Maternal Cigarette Smoke Exposure Exaggerates the Behavioral Defects and Neuronal Loss Caused by Hypoxic-Ischemic Brain Injury in Female Offspring.
Hypoxic-ischemic encephalopathy affects ∼6 in 1,000 preterm neonates, leading to significant neurological sequela (e.g., cognitive deficits and cerebral palsy). Maternal smoke exposure (SE) is one of the common causes of neurological disorders; however, female offspring seems to be less affected than males in our previous study. We also showed that maternal SE exaggerated neurological disorders caused by neonatal hypoxic-ischemic brain injury in adolescent male offspring. Here, we aimed to examine whether female littermates of these males are protected from such insult. BALB/c dams were exposed to cigarette smoke generated from 2 cigarettes twice daily for 6 weeks before mating, during gestation and lactation. To induce hypoxic-ischemic brain injury, half of the pups from each litter underwent left carotid artery occlusion, followed by exposure to 8% oxygen (92% nitrogen) at postnatal day (P) 10. Behavioral tests were performed at P40-44, and brain tissues were collected at P45. Maternal SE worsened the defects in short-term memory and motor function in females with hypoxic-ischemic injury; however, reduced anxiety due to injury was observed in the control offspring, but not the SE offspring. Both hypoxic-ischemic injury and maternal SE caused significant loss of neuronal cells and synaptic proteins, along with increased oxidative stress and inflammatory responses. Oxidative stress and inflammatory response due to maternal SE may be the mechanism of worsened neurological outcomes by hypoxic-ischemic brain injury in females, which was similar to their male littermates shown in our previous study.


Direct detection of the acetate-forming activity of the enzyme acetate kinase.
Acetate kinase, a member of the acetate and sugar kinase-Hsp70-actin (ASKHA) enzyme superfamily, is responsible for the reversible phosphorylation of acetate to acetyl phosphate utilizing ATP as a substrate. Acetate kinases are ubiquitous in the Bacteria, found in one genus of Archaea, and are also present in microbes of the Eukarya. The most well characterized acetate kinase is that from the methane-producing archaeon Methanosarcina thermophila. An acetate kinase which can only utilize PP(i) but not ATP in the acetyl phosphate-forming direction has been isolated from Entamoeba histolytica, the causative agent of amoebic dysentery, and has thus far only been found in this genus. In the direction of acetyl phosphate formation, acetate kinase activity is typically measured using the hydroxamate assay, first described by Lipmann, a coupled assay in which conversion of ATP to ADP is coupled to oxidation of NADH to NAD(+) by the enzymes pyruvate kinase and lactate dehydrogenase, or an assay measuring release of inorganic phosphate after reaction of the acetyl phosphate product with hydroxylamine. Activity in the opposite, acetate-forming direction is measured by coupling ATP formation from ADP to the reduction of NADP(+) to NADPH by the enzymes hexokinase and glucose 6-phosphate dehydrogenase. Here we describe a method for the detection of acetate kinase activity in the direction of acetate formation that does not require coupling enzymes, but is instead based on direct determination of acetyl phosphate consumption. After the enzymatic reaction, remaining acetyl phosphate is converted to a ferric hydroxamate complex that can be measured spectrophotometrically, as for the hydroxamate assay. Thus, unlike the standard coupled assay for this direction that is dependent on the production of ATP from ADP, this direct assay can be used for acetate kinases that produce ATP or PP(i).


Transnitrosylation of XIAP regulates caspase-dependent neuronal cell death.
X-linked inhibitor of apoptosis (XIAP) is a potent antagonist of caspase apoptotic activity. XIAP also functions as an E3 ubiquitin ligase, targeting caspases for degradation. However, molecular pathways controlling XIAP activities remain unclear. Here, we report that nitric oxide (NO) reacts with XIAP by S-nitrosylating its RING domain (forming SNO-XIAP), thereby inhibiting E3 ligase and antiapoptotic activity. NO-mediated neurotoxicity and caspase activation have been linked to several neurodegenerative disorders, including Alzheimer's, Parkinson's, and Huntington's diseases. We find significant SNO-XIAP formation in brains of patients with these diseases, implicating this reaction in the etiology of neuronal damage. Conversely, S-nitrosylation of caspases is known to inhibit apoptotic activity. Unexpectedly, we find that SNO-caspase transnitrosylates (transfers its NO group) to XIAP, forming SNO-XIAP, and thus promotes cell injury and death. These findings provide insights into the regulation of caspase activation in neurodegenerative disorders mediated, at least in part, by nitrosative stress.


The effect of high plasma levels of angiotensin-converting enzyme (ACE) and plasminogen activator inhibitor (PAI-1) on the reperfusion after thrombolytic therapy in patients presented with acute myocardial infarction.
The resistance to thrombolytic agents and delays in reperfusion occur in more than 30% after acute myocardial infarction. This may play an important role in the unsuccessful recanalization after thrombolytic therapy. The aim of this study is to assess the clinical and biochemical markers of reperfusion after different types of thrombolytic therapy and to find out the relationship between PAI-1 and ACE serum levels and the short-term outcome. Pretreatment ACE and PAI-1 plasma levels of 184 patients with acute myocardial infarction, treated with thrombolytic therapy were determined. Failure of thrombolysis was considered when reperfusion was delayed as assessed by noninvasive reperfusion criteria, reinfarction, and impaired left ventricular function. High plasma level of ACE (> 50 U/L), PAI-1 (> 43 ng/ml) and both was found in 57, 108 and 32 patients respectively. Subjects with high ACE plasma levels were characterized by impaired LV systolic function (79.0% vs. 75.0%), new Q-wave (88.4% vs. 74.2%), less reperfusion arrhythmia (19.3% vs. 22.8%) and prolonged hospitalization (70% vs. 66%) but no statistical significance was observed. High enzymes levels of PAI-1 were observed with higher incidence of anterior myocardial infarction (50.0% vs. 41.0%), lesser ST segment resolution (65.6% vs. 58.8%), reinfarction (6.3% vs. 5.9%), and impaired LV systolic function (90.6% vs. 76.0%), and prolonged hospitalization (70.4% vs. 63.4). There was a statistically significant difference between thrombolytic agents in the presence of high ACE regarding hospital overstay (p = 0.02). While the presence of high PAI-1 was significantly affect the degree of ST-segment resolution (p = 0.03). High plasma ACE and/or PAI-1 plays a considerable role in the higher incidence of unsuccessful reperfusion and impaired left ventricular function after thrombolytic therapy. A rapid diagnostic tool that enables physician of detecting those enzymes before giving thrombolytic therapy may change the strategy of treatment to offer another effective revascularization method.


Delivery of optical contrast agents using Triton-X100, part 1: reversible permeabilization of live cells for intracellular labeling.
Effective delivery of optical contrast agents into live cells remains a significant challenge. We sought to determine whether Triton-X100, a detergent commonly used for membrane isolation and protein purification, could be used to effectively and reversibly permeabilize live cells for delivery of targeted optical contrast agents. Although Triton-X100 is widely recognized as a good cell permeabilization agent, no systematic study has evaluated the efficiency, reproducibility, and reversibility of Triton-X100-mediated permeabilization in live mammalian cells. We report a series of studies to characterize macromolecule delivery in cells following Triton-X100 treatment. Using this approach, we demonstrate that molecules ranging from 1 to 150 kDa in molecular weight can be reproducibly delivered into live cells by controlling the moles of Triton-X100 relative to the number of cells to be treated. When Triton-X100 is administered at or near the minimum effective concentration, cell permeabilization is generally reversed within 24 h, and treated cells continue to proliferate and show metabolic activity during the restoration of membrane integrity. We conclude that Triton-X100 is a promising permeabilization agent for efficient and reproducible delivery of optical contrast agents into live mammalian cells.


Peer review in MRI: A quality improvement programme and pilot study.
The aim of this pilot study was to implement a peer review programme to evaluate MRI images and protocols, with the goal of improving quality and standardising protocols. A plan-do-check-act method of action research was adopted. A checklist was designed and two radiographers scored the images (Optimal, Diagnostic or Suboptimal). A sample of five Lumbar Spine examinations were selected and reviewed on two separate occasions, one month apart. A consultant radiologist also scored the selected examinations. There was excellent intra-rater reliability for both observers. At first assessment, Cohen's weighted Kappa analysis indicated moderate inter-rater agreement (0.457) rising to substantial agreement (0.606) at second assessment. Variations in sequence parameter settings by the radiographers were noted. Feedback via educational sessions were implemented and enhancement of protocols were made. Radiographers manipulate many parameters during MRI examinations, and image quality can be degraded if sequences are not optimised. This may lead to misinterpretation. Initial results suggest peer review can result in improved image quality, better protocols, and improved staff confidence. There are opportunity costs involved in releasing staff from clinical work and time and resources required for image appraisal training, however we suggest this model can be extended to other departments and modalities as a healthcare improvement initiative. Initial results suggest peer review processes performed by radiographers can result in improvement to protocols and image quality in MRI. With appropriate training, radiographers can implement and undertake appraisal of image quality in MRI as part of clinical governance. The purpose of feedback must be made clear, and good professional relationships should be forged to allow candid and supportive feedback with a focus on development and education.


Urban wastewater effluent increases antibiotic resistance gene concentrations in a receiving northern European river.
Antibiotic-resistant bacteria are an emerging global problem that threatens to undermine important advances in modern medicine. The environment is likely to play an important role in the dissemination of antibiotic-resistance genes (ARGs) among both environmental and pathogenic bacteria. Wastewater treatment plants (WWTPs) accumulate both chemical and biological waste from the surrounding urban milieu and have therefore been viewed as potential hotspots for dissemination and development of antibiotic resistance. To assess the effect of wastewater effluent on a river that flows through a Swedish city, sediment and water samples were collected from Stångån River, both upstream and downstream of an adjacent WWTP over 3 mo. Seven ARGs and the integrase gene on class 1 integrons were quantified in the collected sediment using real-time polymerase chain reaction (PCR). Liquid chromatography-mass spectrometry was used to assess the abundance of 10 different antibiotics in the water phase of the samples. The results showed an increase in ARGs and integrons downstream of the WWTP. The measured concentrations of antibiotics were low in the water samples from the Stångån River, suggesting that selection for ARGs did not occur in the surface water. Instead, the downstream increase in ARGs is likely to be attributable to accumulation of genes present in the treated effluent discharged from the WWTP.


The structure and function of proteins involved in mammalian pre-mRNA splicing.
Intervening sequences are removed from nuclear pre-mRNAs in a well-defined multi-step pathway. Small nuclear ribonucleoprotein particles (snRNPs) and numerous protein factors are essential for the formation of the active spliceosome in which intron excision proceeds in two successive transesterification reactions. Important elements for catalysis are the RNA moieties of the snRNPs that align the pre-mRNA splice sites in the active center of the spliceosome. Although pre-mRNA splicing is almost certainly RNA-mediated, both snRNA-associated proteins and non-snRNP splicing factors participate in each step of the splicing reaction. Splicing proteins exert auxiliary functions in the recognition, selection, and juxtaposition of the splice sites and drive conformational changes during spliceosome assembly and catalysis. Many splicing factors have been isolated in recent years and corresponding cDNAs have been cloned. This review summarizes the structure and function of mammalian proteins which are essential components of the constitutive splicing machinery.


A designed plasmid-transition strategy enables rapid construction of robust and versatile synthetic exoelectrogens for environmental applications.
Genetic engineering is promising to expand the application scope of exoelectrogens in energy and environmental applications and plasmid vectors, as one type of fundamental tool, are intensively applied. Antibiotics are widely utilized for plasmid selection and maintenance; however, their utilization suffers from environmental concerns on the spread of resistance genes, elevated costs, inevitable genotypic instability and phenotypic heterogeneity. In this work, we establish an auxotrophic complementation system for stable plasmid maintenance without antibiotic association, in Shewanella oneidensis, an attractive model exoelectrogen. A plasmid-transition strategy is designed to facilitate the rapid and efficient construction of the auxotrophic complementation system. Such a system not only enables the same intensive gene expression as the conventional antibiotic-associated plasmid system but also exhibits remarkably superior robustness and stability. With this system, the menaquinone pool of the extracellular respiratory chain is enhanced first independently and further synergized by engineering the Mtr conduit, leading to significantly promoted extracellular electron transfer (EET) outputs (up to 10.33- and 2.97-fold improvement in the maximum current density and the maximum output voltage) and heavy metal Cr(VI) reduction ability (5.15-fold improvement). This work provides a robust and stable platform to engineer exoelectrogens for environmental applications.


On the use of enzyme inhibitors to study the synthesis and utilization of brain GABA.
Changes in the GABA concentration in different parts of the rat brain were studied following inhibition of the glutamic acid decarboxylase or the GABA-alpha-ketoglutaric acid aminotransferase. The GABA concentration was reduced by the decarboxylase inhibitors 4-deoxypyridoxine and isoniazid, but not by 3-mercaptopropionic acid and DL-allylglycine. The aminotransferase inhibitor gamma-acetylenic GABA increased the concentration of GABA and this effect was markedly inhibited by 3-mercaptopropionic acid and partly by 4-deoxypyridoxine and isoniazid. The 4-deoxypyridoxine-induced decrease in GABA concentration was approximately maximal after 400 mg/kg intraperitoneally and 90 min. The brain DOPA decarboxylase activity in vivo was not inhibited by 4-deoxypyridoxine. The GABA concentration in the substantia nigra was reduced by 75 per cent 4 days after section of the striato-nigral GABA neurones. In the denervated substantia nigra, 4-deoxypyridoxine did not change the concentration of GABA whereas the effect of gamma-acetylenic GABA was reduced by 70 per cent.


Identification of human liver diacetyl reductases by nano-liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometry.
Several forms of diacetyl-reducing enzyme were found to exist in the human liver cytosol. Three (DAR-2, DAR-5, and DAR-7) of them were purified as a single band on SDS-PAGE by a combination of a few kinds of column chromatographies. The in-gel tryptic digests of the purified enzymes were analyzed by nano-liquid chromatography (LC)/Fourier transform ion cyclotron resonance mass spectrometry (FT ICR MS), which provided peptide masses at a ppm-level accuracy. The enzymes, DAR-2, DAR-5, and DAR-7, were identified as alcohol dehydrogenase beta subunit (ADH2), carbonyl reductase (CBR1), and aldehyde reductase (AKR1A1), respectively, by peptide mass fingerprinting. In addition, an alternating-scan acquisition of nano-LC/FT ICR mass spectra, i.e., switching of normal acquisition conditions and in-source fragmentation conditions scan by scan, provided sets of parent and fragment ion masses of many of the tryptic peptides in a single LC/MS run. The peptide sequence-tag information at the ppm-level accuracy was used to further confirm the protein identities. It was demonstrated that nano-LC/FT ICR MS can be used for rigorous protein identification at a subpicomole level as an alternative technique to nano-LC/MS/MS.


Combined Use of Specially-Designed Digital Surgical Guides and Pre-Formed Reconstruction Plate to Treat Bilateral Mandibular Fracture.
This paper describes the application of a modified digital surgical guide, an occlusal template and a pre-formed reconstruction titanium plate in the open reduction and internal fixation of a bilateral mandibular fracture. Bilateral mandibular fracture is a commonly encountered simple type of fracture. However, even for an experience surgeon, achieving precise treatment remains a challenge due to the movable temporomandibular joint, unstable fractured segments, the difficulty in forming a reconstruction plate, and the lack of an effective stabilizing and locating device. In this case, the surgeon used a specially-designed modified guide together with a reconstruction plate and an occlusal template to treat a bilateral mandible fracture, effectively improving the accuracy and the medical outcome of the operation, saving operation time and reducing postoperative complications.


Regulation of the mitochondrial permeability transition pore by ubiquinone analogs. A progress report.
The permeability transition pore (PTP) is a mitochondrial inner membrane Ca2+-sensitive channel that plays a key role in different models of cell death. In a series of recent studies we have shown that the PTP is modulated by quinones, and we have identified three functional classes: (i) PTP inhibitors; (ii) PTP inducers; and (iii) PTP-inactive quinones that compete with both inhibitors and inducers. Here, we review our current understanding of pore regulation by quinones, and present the results obtained with a new series of structural variants. Based on the effects of the compounds studied so far, we confirm that minor structural changes profoundly modify the effects of quinones on the PTP. On the other hand, quinones with very different structural features may have qualitatively similar effects on the PTP. Taken together, these results support our original proposal that quinones affect the PTP through a common binding site whose occupancy modulates its open-closed transitions, possibly through secondary changes of the Ca2+-binding affinity.


Vigilance as a caring expression and Leininger's theory of cultural care diversity and universality.
Vigilance, or the close, protective involvement of families caring for hospitalized relatives, was explored in this study using holistic ethnography. Leininger's theory of cultural care diversity and universality provided direction for the researcher to generate substantive data about the meanings, patterns, and day-to-day experience of vigilance. Five categories of meaning were derived from the data: commitment to care, emotional upheaval, dynamic nexus, transition, and resilience. The research findings expand understanding of vigilance as a caring expression, suggest direction for nursing practice, and contribute to Leininger's theory of cultural care diversity and universality and the development of nursing science.


Expression and characterization of single-chain variable fragment antibody against staphylococcal enterotoxin A in Escherichia coli.
The staphylococcal enterotoxins (SEs) are potent gastrointestinal exotoxins synthesized by Staphylococcus aureus, which is responsible for various diseases including septicemia, food poisoning, and toxic shock syndrome, as well as bovine mastitis. Among them, staphylococcal enterotoxin A (SEA) is one of the most commonly present serotypes in staphylococcal food poisoning cases. In this study, the stable hybridoma 3C12 producing anti-SEA monoclonal antibody was established with an equilibrium dissociation constant (KD) of 1.48 × 10(-8) mol·L(-1), its ScFv-coding genes were obtained and then the anti-SEA single chain variable fragment (ScFv) protein was expressed in Escherichia coli. Characterization of the expressed target ScFv protein was analyzed by sodium dodecyl sulfate - polyacrylamide gel electrophoresis, Western blot, and enzyme-linked immunosorbent assay. The results demonstrated that the recombinant anti-SEA ScFv protein retained a specific binding activity for SEA, and the KD value of the soluble ScFv was about 3.75 × 10(-7) mol·L(-1). The overall yield of bioactive anti-SEA ScFv in E. coli flask culture was more than 10 mg·L(-1).


Dispositional optimism and suicide among trans and gender diverse adults.
Trans and gender diverse adults are at increased suicide risk. Optimism protects against suicide across multiple populations. Applying the Interpersonal-Psychological Theory of Suicide (IPTS), we examined both factors among 237 adults recruited via social media and online platforms, 79.3% of whom reported serious suicide ideation. Dispositional optimism predicted suicidal ideation and behaviors (SIB), but did not moderate the relationship between the IPTS components and SIB. After controlling for depressive symptoms, hormone therapy and gender-affirming surgery did not predict SIB. Promoting dispositional optimism within a therapeutic framework may reduce SIB in this vulnerable population.


Fatty Acids and Membrane Lipidomics in Oncology: A Cross-Road of Nutritional, Signaling and Metabolic Pathways.
Fatty acids are closely involved in lipid synthesis and metabolism in cancer. Their amount and composition are dependent on dietary supply and tumor microenviroment. Research in this subject highlighted the crucial event of membrane formation, which is regulated by the fatty acids' molecular properties. The growing understanding of the pathways that create the fatty acid pool needed for cell replication is the result of lipidomics studies, also envisaging novel fatty acid biosynthesis and fatty acid-mediated signaling. Fatty acid-driven mechanisms and biological effects in cancer onset, growth and metastasis have been elucidated, recognizing the importance of polyunsaturated molecules and the balance between omega-6 and omega-3 families. Saturated and monounsaturated fatty acids are biomarkers in several types of cancer, and their characterization in cell membranes and exosomes is under development for diagnostic purposes. Desaturase enzymatic activity with unprecedented de novo polyunsaturated fatty acid (PUFA) synthesis is considered the recent breakthrough in this scenario. Together with the link between obesity and cancer, fatty acids open interesting perspectives for biomarker discovery and nutritional strategies to control cancer, also in combination with therapies. All these subjects are described using an integrated approach taking into account biochemical, biological and analytical aspects, delineating innovations in cancer prevention, diagnostics and treatments.


Characterization of Peroxisomes from the Alga Bumilleriopsis filiformis.
The Xanthophycean alga Bumilleriopsis filiformis possesses peroxisomes which on electron micrographs show a mostly spherical or ovoid shape with a diameter in the range of 0.3 micrometer. Their granular matrix is usually of moderate electron density and in a very few cases contains amorphous inclusions. No associations with other organelles could be observed.During separation in a sucrose gradient, the peroxisomes from Bumilleriopsis equilibrate at a density of 1.22 grams per cubic centimeter. Glycolate oxidase and glyoxylate-glutamate aminotransferase were found in the isolated organelles along with catalase and uricase. However, no further leaf peroxisomal enzymes were detected. This is the first time that an alga of the group of Xanthophyceae has been demonstrated to possess a glycolate oxidase.The organelles from Bumilleriopsis differ from leaf peroxisomes also by the absence of enzymes of the beta-oxidation pathway. All enzymes for the degradation of fatty acids which were tested are located solely in the mitochondria.


Altered matrix metalloproteinase expression associated with oncogene-mediated cellular transformation and metastasis formation.
Matrix metalloproteinase expression was examined in a series of mammalian cell lines of varying degrees of malignant progression. The expression of MMP-2 and MMP-9 was found to correlate with ras-mediated cellular transformation and as a function of malignant potential. Altered MMP-2 and MMP-9 expression was found to correlate also in other oncogene transformed cell lines and the level of expression of both MMP-2 and MMP-9 correlated with metastatic potential. Increased expression of both MMP-2 and MMP-9 was also found in cells which constitutively over-express MAP kinase kinase suggesting that one of the consequences of the persistent activation of the MAP kinase pathway is elevated expression of MMP-2 and MMP-9. Additionally, this study demonstrated a correlation between the expression of MMP-3 (stromelysin-1) and the level of ras expressed in cells and with the cells' ability to form tumors and with malignant potential. The existence of a novel 80 kDa caseinase activity which correlates with ras expression and the ability of the cell to form tumors was also demonstrated. The growth status of transformed cells was also found to be important in determining the expression of MMP-2 mRNA but not MMP-9 mRNA expression, and this expression was cell-type specific. This study also demonstrates that oncogenes can interact to influence and to determine the nature of the matrix metalloproteinases expressed and that this interaction results in a tumorigenic phenotype and, most importantly, contributes to the metastatic phenotype. Alterations in the expression and the regulation of MMPs, particularly MMP-2 and MMP-9, constitute an integral part of the altered growth regulatory program found within transformed cells and in particular, in transformed cells capable of malignant progression.


Hologram interferometry: carrier fringes.
The sensitivity of the interferometric techniques to longitudinal variations of the optical path can be increased by introducing carrier fringes. A new method for introducing such fringes is presented.


Role of Endoscopic Procedures in the Diagnosis of IgG4-Related Pancreatobiliary Disease.
The emergence of the disease entity of glucocorticoid-responsive systemic immunoglobulin G4 (IgG4)-related pancreatobiliary disease has generated substantial attention among the international gastroenterology society. IgG4-related pancreatobiliary disease includes type 1 autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC). The typical manifestations of IgG4-related pancreatobiliary disease are cholestatic liver dysfunction, obstructive jaundice, and weight loss, although it may present with no clinical symptoms. Since it mimics tumors on imaging, AIP/IgG4-SC may often be misdiagnosed as pancreatic or biliary cancer. The endoscopic armamentarium for the diagnosis of IgG4-related pancreatobiliary disease includes endoscopic ultrasonography, intraductal ultrasonography, endoscopic retrograde cholangiopancreatography, and cholangioscopy. The role of endoscopic tissue acquisition is two-fold in the diagnosis of IgG4-related pancreatobiliary disease: exclusion of cancer and procurement of histopathological proof for diagnosis of AIP/IgG4-SC, which can also be achieved by adding the immunohistochemistry for IgG4. Our review article addresses the role of various endoscopic examinations in diagnosing IgG4-related pancreatobiliary disease, focusing on the differentiation of this condition from pancreatobiliary malingnancies.


An Open-Source Wireless Sensor Node Platform with Active Node-Level Reliability for Monitoring Applications.
In wireless sensor networks, the quality of the provided data is influenced by the properties of the sensor nodes. Often deployed in large numbers, they usually consist of low-cost components where failures are the norm, even more so in harsh outdoor environments. Current fault detection techniques, however, consider the sensor data alone and neglect vital information from the nodes' hard- and software. As a consequence, they can not distinguish between rare data anomalies caused by proper events in the sensed data on one side and fault-induced data distortion on the other side. In this paper, we contribute with a novel, open-source sensor node platform for monitoring applications such as environmental monitoring. For long battery life, it comprises mainly low-power components. In contrast to other sensor nodes, our platform provides self-diagnostic measures to enable active node-level reliability. The entire sensor node platform including the hardware and software components has been implemented and is publicly available and free to use for everyone. Based on an extensive and long-running practical experiment setup, we show that the detectability of node faults is improved and the distinction between rare but proper events and fault-induced data distortion is indeed possible. We also show that these measures have a negligible overhead on the node's energy efficiency and hardware costs. This improves the overall reliability of wireless sensor networks with both, long battery life and high-quality data.


[Immobilized forms of daunorubicin in patients with acute leukemia].
To study pharmacokinetics of liposomal daunorubicine DaunoXome and daunorubicine (rubomycin) associated with red cells: to assess their effectiveness and toxicity in patients with acute leukemia. 7 patients with resistant or recurrent acute leukemia entered the trial. Of them 2 patients had acute myeloid leukemia. They received DaunoXome in dose 100 mg in days 1, 2 and 3 of 7 + 3 program. 1 patient had pretreated acute promyelocytic leukemia. This patient received 5-day course of DaunoXome in a dose 100 mg in the presence of ATRA therapy. 4 patients were given single dose daunorubicin associated with autoerythrocytes in the courses RACOP and 7 + 3 in a dose 45 mg/m2. Concentrations of free, bound and liposomal daunorubicin were determined spectrofluorimetrically in chlorophorm extracts of plasm, blood, liquor and bone marrow specimens. Immobilization of daunorubicin on the red cells and liposomes changes pharmacokinetics of the drug: peak concentrations change and the area under the concentration curve increases. Tolerance of DaunoXome and daunorubicine associated with red cells was satisfactory in all the cases: clinical and echo-CG signs of cordiotoxicity were absent, myelotoxicity was similar to that of free daunorubicine. DaunoXome was effective in 2 of 3 patients with acute myeloblastic leukemia. The findings are of practical interest for physicians designing new programs of therapy of acute leukemia.


[Aggressive skin metastasis in lung cancer].
A fifty seven year old male patient was admitted to our clinic because of complaints of cough and sputum. Computed tomography revealed by a 36x25 mm mass on the lateral of the 7th left rib, a 50x52 mm mass on the right main bronchus, growing 40x34 mm lymph nodes on the carina and paratracheal, 60x42 mm mass on the right adrenal and extensive bone metastasis. Squamous cell carcinoma was diagnosed by performed bronchoscopic biopsy. Scalp dermal biopsy was taken upon detection of extensive lesions on the skin.Scalp biopsy was reported squamous cell carcinoma infiltration.The last time when was given radiotherapy to footwell metastasis, the patient was fever and hypotension, we were accepted intensive care unit. In this article, we aimed to discuss rarely aggressive skin metastasis in a squamous cell carcinoma, a type of lung cancerin the light of current literature data.


Site-directed mutagenesis of rabbit proacrosin. Identification of residues involved in zona pellucida binding.
The mammalian acrosomal sperm protease proacrosin plays a role in fertilization by proteolysis of the oocyte's outer investments. In addition to its serine protease activity, acrosin from several species is known to have binding activity for the zona pellucida, and this action may serve to anchor sperm during zona penetration. In this study, proacrosin was purified from acid extracts of rabbit sperm and shown to bind to homologous zona pellucida using an in vitro assay. Measurement of this binding activity indicated a high affinity saturable interaction with a KD = 1.4 x 10(-8) M. Using cDNAs obtained from previously cloned and sequenced rabbit proacrosin and a splice variant that encodes a shorter form of acrosin (Richardson, R. T., and O'Rand, M. G. (1994) Biochim. Biophys. Acta 1219, 215-218), constructs of various sizes were produced using polymerase chain reaction and expressed as recombinant proteins. In the same in vitro zona binding assay, a construct representing residues 1-279 of rabbit proacrosin was found to bind to zona with a high affinity similar to that of native proacrosin, KD = 2.1 x 10(-8) M. By making smaller recombinant fragments and assaying them for zona binding activity, the location of the binding site was mapped to residues 47-94. Protein modeling of rabbit proacrosin using chymotrypsinogen A as a three-dimensional model indicated that an exposed loop Asp35 to His40 in chymotrypsinogen A is extended with an additional five amino acid residues in rabbit proacrosin from Ile43 to His53 containing arginine residues Arg47, Arg50 and Arg51. Site-directed mutagenesis of arginine residues Arg50 and Arg51 to alanine produced a recombinant without significant zona binding activity. These results are consistent with the hypothesis that rabbit proacrosin contains a specific zona pellucida binding site and that the loop containing arginine residues 50 and 51 is critical for zona binding activity.


Management of patients with stunned myocardium associated with subarachnoid hemorrhage.
Cardiac complications are well known after aneurysmal subarachnoid hemorrhage. Electrocardiographic changes occur in 50% to 100% of such cases. Arrhythmias, left ventricular dysfunction, and frank myocardial infarction are infrequently observed. Myocardial infarction must be differentiated from neurogenic stunned myocardium, which is a reversible condition. From 1996 to 2001, 105 patients with aneurysmal subarachnoid hemorrhage underwent endovascular treatment at the University of Michigan. Of these, four patients with no history of cardiac disease experienced cardiac failure related to neurogenic stunned myocardium. All had signs of left ventricular dysfunction, electrocardiographic changes, and elevated cardiac enzymes. Three had pulmonary edema at presentation. All were diagnosed with myocardial infarction. One underwent coronary angiography, which was normal. All were considered poor surgical candidates and underwent endovascular treatment of the aneurysms. Three of four patients developed symptomatic vasospasm, and two required balloon angioplasty. Three patients achieved good outcomes. The eldest died from severe vasospasm that was unresponsive to angioplasty. Reversible cardiac failure associated with subarachnoid hemorrhage may be due the neurogenic stunned myocardium. Frequent symptomatic vasospasm occurs, possibly related to poor cardiac output and the inability to optimize hyperdynamic hypervolemic therapy, particularly with compromised volume status. These patients can be treated with endovascular therapy of the aneurysms and balloon angioplasty as needed. With aggressive management, patients can recover from these reversible cardiac complications.


Novel propanamide analogue and antiproliferative diketopiperazines from mangrove Streptomyces sp. Q24.
A new propanamide analogue (1), along with one known alkaloid (2) and four known diketopiperazines (3-6), was isolated from a cultured broth of the actinomycete Streptomyces sp. Q24 that was obtained from a sample of mangrove soil. The structures of these isolates were characterised as 3-acetylamino-N-2-thienyl-propanamide (1), N-acetyltryptamine (2), cyclo-(l-phenylalanine-l-4-hydroxyproline) (3), cyclo-(l-leucine-l-4-hydroxyproline) (4), cyclo-(l-phenylalanine-d-4-hydroxyproline) (5) and cyclo-(l-leucine-l-proline) (6) based on their NMR and HRESIMS data as well as optical rotation. Three diketopiperazines (3, 4, 6) showed activity in inhibiting the proliferation of human glioma U87-MG and U251 cells. This type of the new propanamide analogue (1) is first found from a nature source and the antiproliferative property of these three diketopiperazines against glioma cells is also reported herein for the first time.


The acute effects of exercise on bone turnover.
Exercise is known to have long-term benefits on bone mass, but little is known about the short-term effects of exercise on bone turnover. The purpose of this study was to investigate whether acute effects of exercise on bone remodelling could be detected by measuring blood and urinary markers of bone turnover. We measured biochemical markers of bone turnover in ten healthy, young men before and up to 32 hours after 30 minutes of brisk treadmill walking. Blood samples were taken before, immediately after and at 0.5, 1, 8, 24 and 32 hours after the exercise. These were assayed for osteocalcin and bone specific alkaline phosphatase. Twenty-four hour urine samples were taken over three days (day before, day of and day after exercise) and measured for pyridinoline and deoxypyridinoline crosslinks. Crosslink excretion was standardised for total body bone mineral content (TBBMC) and urinary creatinine. Total body bone mineral density (and content) and body composition were measured by dual energy X-ray absorptiometry. No changes in the levels of either osteocalcin or alkaline phosphatase were seen at any time point following the exercise. Both urinary crosslinks exhibited an increase in levels on the day of the exercise and a further significant increase the day after (pyridinoline 38.7%, p = 0.05; deoxypyridinoline 42.3%, p = 0.025; median, corrected for TBBMC). There were significant negative correlations between the crosslinks, osteocalcin and body fat percentage. In conclusion, the exercise appears to have stimulated bone resorption within 32 hours of moderate exercise, but there was no measurable effect on bone formation after 32 hours. A longer study period may be necessary to detect changes in bone formation.


Complete mitochondrial genome of the mottled skate: Raja pulchra (Rajiformes, Rajidae).
The complete sequence of mitochondrial DNA of a mottled skate, Raja pulchra was sequenced as being circular molecules of 16,907 bp including 2 rRNA, 22 tRNA, 13 protein-coding genes (PCGs), and an AT-rich control region. The organization of the PCGs is the same as those found in other Rajidae species. The nucleotide of L-strand is composed of 29.8% A, 28.0% C, 27.9% T, and 14.3% G with a bias toward A + T slightly. Twelve of 13 PCGs are initiated by the ATG codon while COX1 starts with GTG. Only ND4 harbors the incomplete termination codon, TA. All tRNA genes have a typical clover-leaf structure of mitochondrial tRNA with the exception of [Formula: see text] which has a reduced DHU arm. This mitogenome will provide essential information for better phylogenetic resolution and precision of the family Rajidae and the genus Raja as well as for establishment of a fish stock recovery plan of the species.


Inferring gene regulatory networks using a time-delayed mass action model.
This paper demonstrates a new time-delayed mass action model which applies a set of delay differential equations (DDEs) to represent the dynamics of gene regulatory networks (GRNs). The mass action model is a classical model which is often used to describe the kinetics of biochemical processes, so it is fit for GRN modeling. The ability to incorporate time-delayed parameters in this model enables different time delays of interaction between genes. Moreover, an efficient learning method which employs population-based incremental learning (PBIL) algorithm and trigonometric differential evolution (TDE) algorithm TDE is proposed to automatically evolve the structure of the network and infer the optimal parameters from observed time-series gene expression data. Experiments on three well-known motifs of GRN and a real budding yeast cell cycle network show that the proposal can not only successfully infer the network structure and parameters but also has a strong anti-noise ability. Compared with other works, this method also has a great improvement in performances.


Molecular characterization of the Babesia caballi rap-1 gene and epidemiological survey in horses in Israel.
Equine piroplasmosis imposes great concerns for the equine industry regarding international horse movement, and therefore requires reliable diagnostic tools. Recent studies from South Africa and Jordan, including a preliminary study in Israel, reported extremely low seroprevalence to Babesia caballi (B. caballi) (0-1%) using the acceptable rhoptry-associated protein-1 (RAP-1) cELISA. In accordance with the study from South Africa demonstrating a significant heterogeneity in the rap-1 gene sequence of South African B. caballi isolates, the objectives of this study were to phylogenetically characterize the rap-1 gene of the Israeli isolates and determine the prevalence of B. caballi in horses in Israel. Out of 273 horses tested using the RAP-1 cELISA, only one was sero-positive, while 9.3% were positive on PCR performed on the rap-1 gene. Phylogenetic analysis of the rap-1 gene grouped the Israeli isolates in a cluster together with the South African strains (99% nt identity), but in a separate cluster from the American/Caribbean strains (81-82% nt identity). These findings support the existence of heterogeneity in the RAP-1 amino-acid sequences of the Israeli and South African isolates as compared to that used in the cELISA commercial kit and raise doubts as to the ability of this assay to serve as a sole regulatory test for international horse movement. Risk factor analysis found management and age to significantly associate with prevalence of B. caballi, as higher prevalence was noted in horses held out on pasture and a negative association was recorded with age. In addition, B. caballi was not detected in horses in the steppe-arid and extreme-arid climatic regions as compared to the wetter regions. Findings of this study emphasize the need to combine several detection methods to ameliorate the control and spread of the disease.


Analytical accuracy and reliability of commonly used nutritional supplements in prostate disease.
We determine the analytical accuracy and reliability of commonly used nutritional supplements for prostate disease by comparing the amounts of active ingredients of several brands of vitamin E, vitamin D, selenium, lycopene and saw palmetto. We also compared the amounts of active compound in different lots of the same brand to determine the consistency of the manufacturing process. Samples purchased at pharmacies and specialty stores were sent for independent chemical analysis. The measured dose was compared to the stated dose on the product label. Analysis of variance was performed to test for significance in interlot reliability. Vitamin E (7 samples) and selenium (5) were within a range of -41% to +57% and -19% to +23% of the stated dosage, respectively. All vitamin D brands (4 samples) were within 15% of the stated dose. Saw palmetto (6 samples) were within a range -97% to +140% of the stated dosages with 3 containing less than 20% of the stated dosages. Lycopene brands were between -38% and +143% of stated dosages. Among the reliability assays 1 of 3 brands of vitamin E, 1 of 2 brands of selenium and 1 of 2 brands of saw palmetto demonstrated statistical differences in interlot dosage (p <0.0055, approximate 20% to 25% differences in dose). The 1 assayed form of vitamin D was reliable between lots. Commonly used nutritional supplements for prostate disease vary widely in measured dose. Saw palmetto demonstrated tremendous variability with some samples containing virtually no active ingredients. In contrast, the more regulated substances we measured, such as vitamins and minerals, demonstrated less variation.


Three-dimensional nanotub submicrometer diffraction gratings for solar cells.
Diffraction gratings are a promising approach for reducing reflection and achieving light-trapping in solar cells. Using square lattices as a base structure, we investigate a novel bi-periodic nanotub three-dimensional grating structure and compare it with established textured structures for thin-film and wafer applications. For wafer application, simulations show that optimal AR coated nanotubs demonstrated solar weighted reflectance (SWR) of 2% compared to AR coated square pyramids with values 1.9%. Nanotubs also show SWR below 8% for polar angles to 60°. Simulated short-circuit current thin-film cells with nanotubs using smaller dimensions show higher yields (3-6 mA/cm2 average) compared to square pyramids. For periods greater than 700 nm at aspect ratios of 0.7 and greater, nanotubs have reduced current attributed to the increased planar surface area of the nanotub base, and evident in increased SWR. A simple nanoimprint lithography process was employed in experiments to define a square array of circular holes, utilizing a polydimethylsiloxane (PDMS) stamp applied onto a sol-gel imprint resist. The underlying silicon was then wet etched to produce the nanotub textures of 200 nm height and 513 nm period. AR coated nanotub wafers were produced via plasma enhanced chemical vapor deposition (PECVD), with an experimental and theoretical SWR of 6.4% and 5.4%, respectively.


Effects of two differently heparin-coated extracorporeal circuits on markers for brain and myocardial dysfunction.
The two most commonly used heparin-coated systems for cardiopulmonary bypass (CPB) are the Carmeda Bio-Active Surface (CBAS) (Medtronic, Minneapolis, MN, USA) and the Duraflo II coating (Baxter Healthcare, Irvine, CA, USA). The two surfaces are technically unequal and previous experimental studies have demonstrated disparities in effects on the immune system and blood cells. However, little is known concerning the influence of the two surfaces on markers for brain and myocardial dysfunction. Forty patients undergoing elective, primary coronary bypass grafting with CPB were prospectively randomized to either the CBAS system or the Duraflo II circuit. During and after CPB, biological markers for brain dysfunction and myocardial injury were analysed. Both markers for brain dysfunction S-100B and neuron-specific enolase (NSE) increased significantly during CPB (p = 0.01). The elevation during bypass correlated significantly with the duration of CPB (r = 0.39 and r = 0.38, respectively, both p < 0.02). NSE was somewhat more elevated in the Duraflo II group at the end of CPB (p = 0.01) and 5 h after CPB (p = 0.02); for S-100B, there were no intergroup differences. Also, the markers related to myocardial injury, myoglobin and creatine kinase (CK-MB) mass increased during CPB (p = 0.01), while elevation of troponin-I occurred 5 h after CPB (p = 0.01). There were no statistically significant intergroup differences. No significant correlation was seen between the release of cardiac markers and the duration of CPB. The clinical course was similar in both groups. Except for a slightly higher elevation of NSE at the end of CPB and 5 h after CPB in the Duraflo II group, there were no significant differences between the CBAS group and the Duraflo II group concerning markers for brain and myocardial dysfunction.


Association of nonsyndromic Wilms tumor with premature centromere division (PCD).
Wilms tumor was discovered in a 22-month-old otherwise healthy girl. Her pretreatment karyotype proved to be normal 46,XX with total premature division (PCD) in 21% of her lymphocyte mitoses. This phenomenon was not seen in the parents. PCD was found in less than 4% of lymphocyte mitoses of five other children with Wilms tumor. The individual finding provides further evidence for a relation of PCD to tumorigenesis; however, elucidation of the question needs further systematic studies.


Integrative analysis of miRNA and mRNA paired expression profiling of primary fibroblast derived from diabetic foot ulcers reveals multiple impaired cellular functions.
Diabetic foot ulcers (DFUs) are one of the major complications of diabetes. Its molecular pathology remains poorly understood, impeding the development of effective treatments. Although it has been established that multiple cell types, including fibroblasts, keratinocytes, macrophages, and endothelial cells, all contribute to inhibition of healing, less is known regarding contributions of individual cell type. Thus, we generated primary fibroblasts from nonhealing DFUs and evaluated their cellular and molecular properties in comparison to nondiabetic foot fibroblasts (NFFs). Specifically, we analyzed both micro-RNA and mRNA expression profiles of primary DFU fibroblasts. Paired genomic analyses identified a total of 331 reciprocal miRNA-mRNA pairs including 21 miRNAs (FC > 2.0) along with 239 predicted target genes (FC > 1.5) that are significantly and differentially expressed. Of these, we focused on three miRNAs (miR-21-5p, miR-34a-5p, miR-145-5p) that were induced in DFU fibroblasts as most differentially regulated. The involvement of these microRNAs in wound healing was investigated by testing the expression of their downstream targets as well as by quantifying cellular behaviors in prospectively collected and generated cell lines from 15 patients (seven DFUF and eight NFF samples). We found large number of downstream targets of miR-21-5p, miR-34a-5p, miR-145-5p to be coordinately regulated in mRNA profiles, which was confirmed by quantitative real-time PCR. Pathway analysis on paired miRNA-mRNA profiles predicted inhibition of cell movement and cell proliferation, as well as activation of cell differentiation and senescence in DFU fibroblasts, which was confirmed by cellular assays. We concluded that induction of miR-21-5p, miR-34a-5p, miR-145-5p in DFU dermal fibroblasts plays an important role in impairing multiple cellular functions, thus contributing to overall inhibition of healing in DFUs.


Interface between obesity with dysfunctional metabolism and inflammation, and the triple-negative breast cancer in African American women.
Obesity has dramatically increased over the past fifty years. In the last decade, it has been noted that augmented body mass, metabolic abnormalities, and the relevant "obese" tumor microenvironment (TME) are connected with signaling molecular networks, which in turn, may contribute to aggressive tumor biology in some patients with breast malignancies. This article presents the associations between obesity, metabolic derangements, inflammatory processes in the adipose tissue or TME, and aggressive behavior of triple-negative breast cancer (TNBC) in African American (AA) women. It also describes some abnormal molecular signaling patterns in the "obese" TME with relevance to TNBC biology. Ethnic disparities in TNBC can be due to a variety of biological features (e.g., genetic mutations and tumor heterogeneity), comorbidities (e.g., cardio-metabolic diseases, including diabetes mellitus), and reproductive factors (e.g., multiparty or short breastfeeding period). Such a constellation of biological variables potentially leads to the association between obesity, metabolic derangements, inflammatory processes in the adipose tissue or TME, and aggressive behavior of TNBC in AA women. Since the TNBC and its TME can display very aggressive behavior, it is crucial that the afflicted AA women make efforts to maintain healthy body weight, "flexible" metabolism, and a well-functioning immune system. Further studies are merited to explore the multi-disciplinary factors that can affect TNBC prevention, management, and outcomes to optimize treatment strategies and survival among AA women.


Craniomandibular signals of diet in adapids.
The craniomandibular morphology of the adapid primates of Europe, especially Adapis and Leptadapis (sensu lato), suggests that they possessed enormous jaw adductor muscles. The goal of this study is to estimate jaw adductor muscle mass, physiological cross-sectional area (PCSA), and fiber length in adapid primates from the Eocene of Europe. We also estimated muscle leverage, bite force, and gape parameters. We use bony morphology and osteological correlates of soft tissues in a sample of extant strepsirrhines to estimate these soft-tissue and performance variables in Adapis and Leptadapis. Our results suggest that, compared to a broad sample of extant strepsirrhines, Adapis and Leptadapis had relatively great jaw adductor muscle mass, PCSA, and bite force. They had moderately great jaw adductor leverage but no sign of adaptation for wide gapes. There is no support for the hypothesis that either adapid was a gouger. Our estimates support the inference that Adapis and Leptadapis were primarily folivorous, perhaps also consuming small to medium-sized tough fruits, nuts, and seeds. Explanations for the likely extreme development of the jaw adductor muscles in adapids remain speculative. These include (1) foods that were generally tougher and/or of higher yield strength than those eaten by strepsirrhines today, (2) using the muscles "in shifts" to avoid muscle fatigue in the context of an obdurate diet, and (3) potential constraints on reshaping of the skull for more efficient food processing.


Research agenda.
THIS ISSUE OF JERHRE introduces the concept of hidden ethics---empirical data relevant to ethical problem-solving that does not appear in the ethics literature and is difficult to access. Three related research agendas are suggested concerning methods of finding this literature, scope of inquiry, and synthesis of new knowledge about ethical problem-solving. This issue also introduces the complexities and uncertainties that face persons when deciding whether to participate in Phase 1 and Phase 2 trials. Finally, it introduces a rigorous statistical approach to determining whether an incentive can be large enough to influence subjects to take risks they ordinarily would not take, and thus sets as a research agenda the further exploration of the generalizability of this method and the current findings.


C-Type Lectin Maintains the Homeostasis of Intestinal Microbiota and Mediates Biofilm Formation by Intestinal Bacteria in Shrimp.
Intestinal microbiota are closely related to host physiology. Over the long course of evolution and interaction, both commensal bacteria and their host have evolved multiple strategies to adapt to each other. However, in invertebrates, the regulatory mechanism of intestinal microbiota homeostasis is largely unknown. In the current study, a digestive tract-specific C-type lectin, designated as CTL33, was identified because of its abundance and response to bacteria in the intestine of kuruma shrimp (Marsupenaeus japonicus). Silencing of CTL33 expression led directly to intestinal dysbiosis, tissue damage, and shrimp death. CTL33 could facilitate biofilm formation by the intestinal bacteria. This function originated from its unique architecture, with a lectin domain responsible for bacteria recognition and a coiled coil region that mediated CTL33 dimerization and cross-linked the bacteria into a biofilm-like complex. By mediating the formation of a biofilm, CTL33 promoted the establishment of intestinal bacteria in intestine and maintained the homeostasis of the microbiota. Thus, to our knowledge, we demonstrated a new mechanism of C-type lectin-mediated biofilm formation by intestinal bacteria, providing new insights into intestinal homeostasis regulation in invertebrates.


Lack of effects of recombinant growth hormone on muscle function in patients requiring prolonged mechanical ventilation: a prospective, randomized, controlled study.
To evaluate the benefit of recombinant human growth hormone administration on muscle strength and duration of weaning in critically ill patients undergoing prolonged mechanical ventilation. Prospective, randomized, controlled, single-blind study. Intensive care unit. Twenty patients requiring > or = 7 days of mechanical ventilation for acute respiratory failure. Random assignment to receive either 0.43 IU (approximately 0.14 mg) recombinant growth hormone/kg body weight/day (treated group), or saline (nontreated group) for 12 days. Nutritional support was guided by indirect calorimetry. Cumulative nitrogen balance was positive throughout the study period in the treated group 17.3 (44.9 +/- 17.3[SEM] g/12 days) vs. the nontreated group (-65.8 +/- 11.8 g/12 days) (p<.0001). Despite similar initial plasma concentrations, recombinant growth hormone supplementation resulted in marked increases in growth hormone, insulin like growth factor-1, and insulin concentrations (p<.05, .02, and .0001, respectively, vs. nontreated group). Body impedance determined net fat-free mass increased in the treated group (0.8 +/- 0.6 kg) vs. the nontreated group (-1.1 +/- O.5 kg) (p<.03). Initial peripheral muscle function, assessed by computer-controlled electrical stimulation of the adductor pollicis, was similarly lower in treated and nontreated groups than sex and age-matched normal controls, and decreased further during the study period. Arterial blood gases, cumulative total mechanical ventilation time, and number of hrs/day of mechanical ventilation during weaning were similar in both patient groups. Only three of the ten patients in each group were weaned from mechanical ventilation by day 12. Daily administration of recombinant growth hormone in mechanically ventilated patients with acute respiratory failure promotes a marked nitrogen retention. However, this reaction is accompanied neither by an improvement in muscle strength nor by a shorter duration of ventilatory supports.


X-ray crystallographic studies for ligand-protein interaction changes in rhodopsin.
G-protein-coupled receptors constitute the largest transmembrane receptor family in human. They are generally activated on binding their specific ligands at the extracellular side of membranes. The signal carried by an agonist is then transmitted to the intracellular side through a conformational change of the receptor, which becomes competent to catalyse GDP/GTP exchange in the alpha-subunit of heterotrimeric G-protein. Since most of the G-protein-coupled receptors (rhodopsin-like subfamily) share a set of conserved amino acid residues in the transmembrane domain, it is probable that the ligand-triggered activation process involves a common mechanism of rearrangement of the hepta-helical transmembrane bundle. For understanding the nature of this event that is not yet characterized sufficiently, X-ray crystallographic studies of rhodopsin with or without light stimulation can provide valuable information. In rhodopsin, the initial cis-trans photoisomerization of retinal chromophore triggers the structural changes of transmembrane helices. This activation process has been characterized with some spectroscopically distinct photoreaction intermediates (batho, lumi, Meta I and Meta II). With recent advances in the conditions for crystallographic experiments, the diffraction limit of the rhodopsin crystals has been substantially extended. As a result, it becomes possible to detect small structural changes evoked after photoactivation under cryogenic conditions.


Interactive effects of team cohesion on perceived efficacy in semi-professional sport.
The present study examined the relationships among cohesion, self-efficacy, coaches' perceptions of their players' efficacy at the individual level and athletes' perceptions of their teammates' efficacy. Participants (n = 76) recruited from four semi- professional soccer and basketball teams completed cohesiveness and efficacy questionnaires who. Data were analyzed through a correlational methodology. Results indicated significant correlations between self-efficacy and task cohesion and social cohesion. Regression analysis results suggest task cohesion positively related to coaches and teammate's perception of efficacy. These results have implications for practitioners in terms of the importance of team building to enhance team cohesion and feelings of efficacy. Key pointsThis paper increases the knowledge about soccer and basketball match analysis.Give normative values to establish practice and match objectives.Give applications ideas to connect research with coaches' practice.


A bizarre abdominal cystic lesion.
In spite of careful intraoperative precautions and gauze counts, mistakes can still occur during surgery. In the case reported, a retained gauze leaved during a surgical approach for removing a solid-cystic papillary tumor localized in the pancreatic tail, caused both persistent abdominal discomfort and the presence of an abdominal cystic lesion at imaging techniques. When a previous operative history is present, a foreign body should be taken into account in the differential diagnosis of a patient with an intra-abdominal cystic mass. Finally, radio-opaque marker should be routinely used by surgeons in order to reach a correct diagnosis in operated patients having retained gauze.


Search for I-A trans-complementation affecting the anti-thy-1 response in mice: a final report.
Twenty-nine different F1 hybrids were tested for the possible effect of the H-2 (I-A) heterozygosity purportedly mediated by I-A trans-complementation, on the magnitude of the anti-Thy-1 response. Although the hybrids tested responded well to immunization with Thy-1 disparate thymocytes from donors H-2 compatible with one of the parents they responded poorly when immunized with thymocytes from donors H-2 incompatible with both parents. Preliminary data suggest that H-2 heterozygosity may exert a small but definite effect in H-2r/H-2f hybrids.


Backscatter by azimuthally oriented ice crystals of cirrus clouds.
The backscattering Mueller matrix has been calculated for the first time for the hexagonal ice columns and plates with both zenith and azimuth preferential orientations. The possibility of a vertically pointing polarization lidar measuring the full Mueller matrix for retrieving the orientation distributions of the crystals is considered. It is shown that the element m44 or, equivalently, the circular depolarization ratio distinguishes between the low and high zenith tilts of the crystals. Then, at their low or high zenith tilts, either the element m22 or m34, respectively, should be measured to retrieve the azimuth tilts.


Bone non-union after osteotomy in patients treated with methotrexate.
We describe 2 men with seronegative rheumatoid arthritis who presented non-union of bone after osteotomy of the tibia in one case and of a metatarsal bone in the second. Both patients were still being treated with oral low doses of methotrexate (MTX). After MTX was stopped, a prompt healing of the bone occurred. These observations suggest that MTX should be stopped temporarily in cases with delayed bone healing after surgery.


Topological charge-entropy scaling in kagome Chern magnet TbMn6Sn6.
In ordinary materials, electrons conduct both electricity and heat, where their charge-entropy relations observe the Mott formula and the Wiedemann-Franz law. In topological quantum materials, the transverse motion of relativistic electrons can be strongly affected by the quantum field arising around the topological fermions, where a simple model description of their charge-entropy relations remains elusive. Here we report the topological charge-entropy scaling in the kagome Chern magnet TbMn6Sn6, featuring pristine Mn kagome lattices with strong out-of-plane magnetization. Through both electric and thermoelectric transports, we observe quantum oscillations with a nontrivial Berry phase, a large Fermi velocity and two-dimensionality, supporting the existence of Dirac fermions in the magnetic kagome lattice. This quantum magnet further exhibits large anomalous Hall, anomalous Nernst, and anomalous thermal Hall effects, all of which persist to above room temperature. Remarkably, we show that the charge-entropy scaling relations of these anomalous transverse transports can be ubiquitously described by the Berry curvature field effects in a Chern-gapped Dirac model. Our work points to a model kagome Chern magnet for the proof-of-principle elaboration of the topological charge-entropy scaling.


Detection of an adherence factor of enteropathogenic Escherichia coli with a DNA probe.
A DNA probe to detect genes conferring localized adherence of enteropathogenic Escherichia coli (EPEC) to Hep-2 cells was evaluated by using E. coli isolates from the stools of Peruvian infants with and without diarrhea. The probe was both sensitive and specific and revealed that Hep-2 adherence (because of the EPEC adherence factor [EAF] was more frequent in some O serogroups of EPEC than in others. Those serogroups in which EAF is almost always found have been designated class I EPEC; serogroups in which EAF is rarely found have been designated class II. Both class I (EAF-positive) and class II EPEC are associated with diarrheal disease.


In vitro studies to investigate the reasons for the low potency of cholestyramine and colestipol.
The association rates, dissociation rates, and equilibrium binding of bile acids with cholestyramine and colestipol were measured under physiological conditions with the most abundant bile acids found in humans. Cholestyramine and colestipol equilibrated with the bile acids (5 mM) within 1 h and they bound > 58% and > 17% of the bile acid, respectively, when at equilibrium with physiological concentrations of bile acid (4.3-10.1 mM). However, the conjugated trihydroxy bile acids taurocholic acid and glycocholic acid dissociated rapidly from both cholestyramine and colestipol when the sequestrants, preloaded with the bile acid, were washed with the Krebs-Henseleit buffer. The taurine-conjugated and dihydroxy bile acids dissociated more slowly from cholestyramine and colestipol than the glycine-conjugated and trihydroxy bile acids and, therefore, would be expected to avoid reabsorption to a greater extent by the terminal ileum and colon in vivo. We predict from these results that the reasons for the low potency of cholestyramine and colestipol are that they bind a relatively small proportion of the trihydroxy bile acids in the duodenum and jejunum and that all of the bile acids dissociate to varying extents from the sequestrants in the terminal ileum where the unbound bile acids are reabsorbed by the gut.


Bone marrow transplantation attenuates the myopathic phenotype of a muscular mouse model of spinal muscular atrophy.
Bone marrow (BM) transplantation was performed on a muscular mouse model of spinal muscular atrophy that had been created by mutating the survival of motor neuron gene (Smn) in myofibers only. This model is characterized by a severe myopathy and progressive loss of muscle fibers leading to paralysis. Transplantation of wild-type BM cells following irradiation at a low dose (6 Gy) improved motor capacity (+85%). This correlated with a normalization of myofiber number associated with a higher number of regenerating myofibers (1.6-fold increase) and an activation of CD34 and Pax7 satellite cells. However, BM cells had a very limited capacity to replace or fuse to mutant myofibers (2%). These data suggest that BM transplantation was able to attenuate the myopathic phenotype through an improvement of skeletal muscle regeneration of recipient mutant mice, a process likely mediated by a biological activity of BM-derived cells. This hypothesis was further supported by the capacity of muscle protein extracts from transplanted mutant mice to promote myoblast proliferation in vitro (1.6-fold increase). In addition, a tremendous upregulation of hepatocyte growth factor (HGF), which activates quiescent satellite cells, was found in skeletal muscle of transplanted mutants compared with nontransplanted mutants. Eventually, thanks to the Cre-loxP system, we show that BM-derived muscle cells were strong candidates harboring this biological activity. Taken together, our data suggest that a biological activity is likely involved in muscle regeneration improvement mediated by BM transplantation. HGF may represent an attractive paracrine mechanism to support this activity.


Resting-State Networks of Adolescents Experiencing Depersonalization-Like Illusions: Cross-sectional and Longitudinal Findings.
The mirror-gazing task (MGT) experimentally induces illusions, ranging from simple color changes in the specular image of oneself, to depersonalization-like anomalous self-experiences (ASE) as in experiencing one's specular image as someone else. The objective was to characterize how connectivity in resting-state networks (RSNs) differed in adolescents reporting such depersonalization-like ASEs during the MGT, in a cross-sectional (Y1) and in a longitudinal manner (a year after). 75 adolescents were recruited; for the cross-sectional analysis, participants were split into 2 groups: those who reported depersonalization-like ASEs on the MGT (ASE), and those who did not (NoASE). For the longitudinal analysis, participants were split into 3 groups whether they experienced MGT depersonalization-like ASEs: only at Y1 (Remitters), both times (Persisters), or never (Controls). Participants also filled out self-reports assessing schizotypal personality (Schizotypal Personality Questionnaire [SPQ]), and underwent resting-state functional MRI procedure (rs-fMRI). A group level Independent Component Analysis (ICA) was conducted and voxel-wise inter-group differences within RSNs were examined. The rs-fMRI analysis revealed lower connectivity of specific visual areas within the primary visual network (PVN), and higher connectivity of regions within the Default Mode Network (DMN) when contrasting the ASE and NoASE groups. The areas that were atypically connected within the PVN further presented differential pattern of connectivity in the longitudinal analysis. Atypical connectivity of visual area within the DMN at Y1 was associated with higher scores on the disorganized dimension of schizotypy at the second evaluation. The present study uncovers a subtle signature in the RSNs of non-clinical adolescents who experienced task-induced ASEs.


Skin permeation enhancement of diclofenac by fatty acids.
This study systematically investigated the enhancing effect of fatty acids on the skin permeation of diclofenac. The fatty acids were evaluated in terms of their carbon-chain length, the degree of unsaturation, and their functional groups. The rat-skin permeation rates of diclofenac, saturated in propylene glycol (PG) containing 1% (w/v) fatty acid, were determined using the Keshary-Chien diffusion cells at 37 degrees C. The effect of fatty acids on the saturated solubility of diclofenac in PG was also determined at 37 degrees C using high-performance liquid chromatography. Among the saturated fatty acids tested, palmitic acid (C16:0) showed the most potent skin permeation-enhancing effect. A parabolic correlation was observed between the enhancement effect and the fatty acid carbon-chain length among these saturated fatty acids of C12-C20 units. For the monounsaturated fatty acid series, an increase in permeation was observed as the carbon-chain length increased, and oleic acid (C18:1) showed the highest permeation-enhancing effect. Increasing the number of double bonds in the octadecanoic acids resulted in a parabolic effect in the permeation of diclofenac, revealing oleic acid as the most effective enhancer used in this study. When the carboxylic acid moiety of oleic acid was changed to an amide (oleamide) or hydroxyl (oleyl alcohol) group, a decrease in permeation activity was observed. These results, therefore, suggest that the cis-monounsaturated configuration and the carboxylic acid moiety of an 18-carbon unit fatty acid in PG are the optimum requirements for the effective skin permeation of diclofenac.


A comparative study of the accurate measurement of endotoxin in liposome-encapsulated hemoglobin.
We have examined three different methods of endotoxin determination utilizing the Limulus Amebocyte Lysate (LAL) assay to accurately determine endotoxin levels in Liposome Encapsulated Hemoglobin (LEH), 1) the gel-clot method, 2) chromogenic spectroscopic-based LAL, and 3) the turbidimetric method which determines endotoxin levels in solutions based on the time needed to reach a specific degree of turbidity. Both the chromogenic and turbidimetric methods require significant dilution of the LEH preparation before accurate measurement can be made. We have tested the levels of endotoxin in LEH solutions using these methods and measured LEH, liposome, and hemoglobin samples spiked with known amounts of endotoxin. A comparison of the three methods shows that the absolute value of endotoxin measured in LEH by the three methods can vary significantly. However, within any one assay the spiked amount of endotoxin in the sample can be accurately measured. The accuracy of these methods may also be complicated by the binding of endotoxin to LEH. This was evident by mixing free endotoxin with LEH followed by centrifugation to separate the LEH. Biological activity of endotoxin bound to LEH was measured by exposure to RAW264.7 followed by the expression of tumor necrosis factor.


Interleukin 3-dependent, asialo-GM1-positive cell line with natural cytotoxic but without natural killer cytotoxic activity.
IL-3-dependent cell line (designated as A-3) from adherent spleen cells was developed. The surface phenotype of A-3 cells was analysed by flow cytometry and determined as ASGM1+, FcR+, Ia+. There was no expression of T cell markers (Th1-CD3-CD4-CD8-), B cell marker (surface Ig) as well as macrophage marker Mac-1 antigen. Although A-3 cells expressed ASGM1, they are lacking NK cytotoxic activity in 4 h Cr release assay with YAC-1 targets. In contrast, A-3 cells are endowed with NC cytotoxic activity as shown in 18 h Cr release assay with WEHI-164 target cells.


Characterization of Two Toxin-Antitoxin Systems in Deep-Sea Streptomyces sp. SCSIO 02999.
Toxin-antitoxin (TA) systems are ubiquitous and abundant genetic elements in bacteria and archaea. Most previous TA studies have focused on commensal and pathogenic bacteria, but have rarely focused on marine bacteria, especially those isolated from the deep sea. Here, we identified and characterized three putative TA pairs in the deep-sea-derived Streptomyces sp. strain SCSIO 02999. Our results showed that Orf5461/Orf5462 and Orf2769/Orf2770 are bona fide TA pairs. We provide several lines of evidence to demonstrate that Orf5461 and Orf5462 constitute a type-II TA pair that are homologous to the YoeB/YefM TA pair from Escherichia coli. Although YoeB from SCSIO 02999 was toxic to an E. coli host, the homologous YefM antitoxin from SCSIO 02999 did not neutralize the toxic effect of YoeB from E. coli. For the Orf2769/Orf2770 TA pair, Orf2769 overexpression caused significant cell elongation and could lead to cell death in E. coli, and the neighboring Orf2770 could neutralize the toxic effect of Orf2769. However, no homologous toxin or antitoxin was found for this pair, and no direct interaction was found between Orf2769 and Orf2770. These results suggest that Orf2769 and Orf2770 may constitute a novel TA pair. Thus, deep-sea bacteria harbor typical and novel TA pairs. The biochemical and physiological functions of different TAs in deep-sea bacteria warrant further investigation.


Modern foraging: Presence of food and energy density influence motivational processing of food advertisements.
More energy dense foods are preferable from an optimal foraging perspective, which suggests these foods are more motivationally relevant due to their greater capability of fulfilling biological imperatives. This increase in motivational relevance may be exacerbated in circumstances where foraging will be necessary. This study examined how food energy density and presence of food in the immediate environment interacted to influence motivational processing of food advertisements. N = 58 adults viewed advertisements for foods varying in energy density in contexts where the advertised food was actually present in the viewing room or not. Advertisements for more energy dense foods elicited greater skin conductivity level compared to ads for less energy dense foods when food was not present. All ads elicited decreases in corrugator supercilii activation indicating positive emotional response resultant from appetitive motivational activation, though the greatest activation was exhibited toward higher energy density foods when food was present. This supports an optimal foraging perspective and has implications for healthy eating interventions.


β-Sitosterol induces G1 arrest and causes depolarization of mitochondrial membrane potential in breast carcinoma MDA-MB-231 cells.
It is suggested that dietary phytosterols, such as β-sitosterol (ST), have cancer chemopreventive effects; however, studies are limited to support such claims. Here, we evaluated the efficacy of ST on three different human cancer cell lines including skin epidermoid carcinoma A431 cells, lung epithelial carcinoma A549 cells and breast adenocarcinoma MDA-MB-231. Cell growth assay, cell cycle analysis, FACS, JC-1 staining, annexin V staining and immunoblotting were used to study the efficacy of ST on cancer cells. ST (30-90 μM) treatments for 48 h and 72 h did not show any significant effect on cell growth and death in A431 cells. Whereas similar ST treatments moderately inhibited the growth of A549 cells by up to 13% (p ≤ 0.05) in 48 h and 14% (p ≤ 0.05-0.0001) in 72 h. In MDA-MB-231 cells, ST caused a significant dose-dependent cell growth inhibition by 31- 63% (p ≤ 0.0001) in 48 h and 40-50% (p ≤ 0.0001) in 72 h. While exploring the molecular changes associated with strong ST efficacy in breast cancer cells, we observed that ST induced cell cycle arrest as well as cell death. ST caused G0/G1 cell cycle arrest which was accompanied by a decrease in CDK4 and cyclin D1, and an increase in p21/Cip1and p27/Kip1 protein levels. Further, cell death effect of ST was associated with induction of apoptosis. ST also caused the depolarization of mitochondrial membrane potential and increased Bax/Bcl-2 protein ratio. These results suggest prominent in vitro anti-proliferative and pro-apoptotic effects of ST in MDA-MB-231 cells. This study provides valuable insight into the chemopreventive efficacy and associated molecular alterations of ST in breast cancer cells whereas it had only moderate efficacy on lung cancer cells and did not show any considerable effect on skin cancer cells. These findings would form the basis for further studies to understand the mechanisms and assess the potential utility of ST as a cancer chemopreventive agent against breast cancer.


Candida endocarditis. A treatable form of pacemaker infection.
Fungal endocarditis is a rare complication of permanent pacemaker implantation. In all reports we have identified, this infection has been fatal, diagnosed postmortem. We present a patient in whom early echocardiographic diagnosis resulted in curative surgical and antimicrobial therapy. Fungal endocarditis is an unusual, but treatable complication of permanent pacemakers.


Order on the possession, distribution, dispensing, and administration of the pharmaceutical specialty Mifegyne 200 mg. in tablet form, 28 December 1988.
This French Order has been made having regard to an Order of 22 November 1988 inserting Mifepristone (RU 486) in division II of Schedule A of the Poisons Schedules. The following are among the principal provisions. Division I sets out duties of the manufacturer and wholesale distributors of the pharmaceutical specialty Mifegyne 200 mg in tablet form (Sections 1-5). Under Section 2, pharmaceutical establishments manufacturing or distributing this specialty must keep it in locked cupboards or premises. Under Section 3, every purchase or transfer by a wholesale pharmaceutical establishment, even without charge, must be recorded in a special register, following the procedures indicated. Requirements as to reporting are laid down in Section 4. The register referred to in Section 3 must be retained for 10 years. Division II covers the purchase of the pharmaceutical specialty Mifegyne 200 mg, in tablet form, by establishments performing voluntary terminations of pregnancy, and the dispensing and administration of this specialty (Sections 6-16). Detailed provisions are laid down concerning the procedures to be followed in purchasing, dispensing, etc. the specialty. In particular, a special numbered booklet is to be kept, containing a series of vouchers. The procedures for completing such vouchers and the conditions for their retention are indicated. Under Section 13, pharmacists may supply the specialty only to physicians entitled to prescribe it (and with their names and signatures filed with the pharmacist) or to the person in charge of a department in which voluntary terminations of pregnancy are performed. Section 14 lays down that only physicians performing such terminations are authorized to prescribe and administer this specialty. It is laid down in Section 15 that the pharmacist is to undertake, in the presence of the director of the establishment, a monthly inspection of the cupboard within the department where the specialty is kept.


Identifying efficient agricultural irrigation strategies in Crete.
Water scarcity and droughts are a major concern in most Mediterranean countries. Agriculture is a major user of water in the region and releases significant amounts of surface and ground waters, endangering the sustainable use of the available resources. Best Management Practices (BMPs) can mitigate the agriculture impacts on quantity of surface waters in agricultural catchments. However, identification of efficient BMPs strategies is a complex task, because BMPs costs and effectiveness can vary significantly within a basin. In this study, sustainable agricultural practices were studied based on optimal allocation of irrigation water use for dominant irrigated crops in the island of Crete, Greece. A decision support tool that integrates the Soil and Water Assessment Tool (SWAT) watershed model, an economic model, and multi-objective optimization routines, was used to identify and locate optimal irrigation strategies by considering crop water requirements, impact of irrigation changes on crop productivity, management strategies costs, and crop market prices. Three spatial scales (crop type, fields, and administrative regions) were considered to point out different approaches of efficient management. According to the analysis, depending on the spatial scale and complexity of spatial optimization, water irrigation volumes could be reduced by 32%-70% while preserving current agricultural benefit. Specific management strategies also looked at ways to relocate water between administrative regions (4 prefectures in the case of Crete) to optimize crop benefit while reducing global water use. It was estimated that an optimal reallocation of water could reduce irrigation water volumes by 52% (148 Mm3/y) at the cost of a 7% (48 M€) loss of agricultural income, but maintaining the current agricultural benefit (626.9 M€). The study showed how the identification of optimal, cost-effective irrigation management strategies can potentially address the water scarcity issue that is becoming crucial for the viability of agriculture in the Mediterranean region.


Application-Driven Material Design of Printable Strain Hardening Cementitious Composites (SHCC).
The creation of concrete shells from customized prefabricated modules is a novel approach that facilitates the construction of free-form surfaces considerably. In the framework of the Adaptive Concrete Diamond Construction (ACDC) project at TU Dresden, a material for 3D printing of the outer contours of such modules has been developed based on the principles of Strain Hardening Cementitious Composite (SHCC). In addition to its high ductility, the required material must also be suitable for 3D printing while enabling the achievement of high geometric accuracy in the manufacture of the modules. To gain the required performance, cellulose ether and starch ether were used specifically to extend the open time, for a longer period of maintaining initial workability, as well as for enhancing shape stability and surface quality. An extensive experimental program was carried out to evaluate the outcomes of the material modifications, including flow table tests, water retention tests, and several specific tests to determine the adhesiveness of the fresh SHCC. For hardened SHCC, surface roughness was assessed using a laser 3D scanner in addition to testing its mechanical properties.


Contribution of neutrophil-derived myeloperoxidase in the early phase of fulminant acute respiratory distress syndrome induced by influenza virus infection.
Because the pathogenesis of acute respiratory distress syndrome (ARDS) induced by influenza virus infection remains unknown, we can only improve on existing therapeutic interventions. To approach the subject, we investigated immunological etiology focused on cytokines and an acute lung damage factor in influenza-induced ARDS by using a PR-8 (A/H1N1)-infected mouse model. The infected mouse showed fulminant severe pneumonia with leukocyte infiltration, claudin alteration on tight junctions, and formation of hyaline membranes. In addition to interferon (IFN)-α, plenty of keratinocyte-derived chemokines (KC), macrophage inflammatory protein 2 (MIP-2), regulated on activation normal T-cell expressed and secreted (RANTES), and monocyte chemotactic protein 1 (MCP-1) were significantly released into bronchoalveolar lavage fluid (BALF) of the model. We focused on neutrophil myeloperoxidase (MPO) as a potent tissue damage factor and examined its contribution in influenza pneumonia by using mice genetically lacking in MPO. The absence of MPO reduced inflammatory damage with suppression of leakage of total BALF proteins associated with alteration of claudins in the lung. MPO(-/-) mice also suppressed viral load in the lung. The present study suggests that MPO-mediated OCl(-) generation affects claudin molecules and leads to protein leakage and viral spread as a damage factor in influenza-induced ARDS.