[Physical activity assessment using accelerometry].
Physical activity is an important determinant of health in children and adults. Assessment of physical activity is therefore an important factor in the promotion of health and in several childhood and adulthood pathological situations. Physical activity can be estimated by various methods: pedometry, heart rate monitoring, questionnaires, the doubly labelled water method, and accelerometry. The choice of the type of device depends on the objectives of the clinician or researcher. Accelerometry currently represents the best objective method for measuring physical activity and is widely used in clinical or epidemiological studies. The purpose of this paper is to help practitioners and researchers to make better decisions when using accelerometry as a device for measuring physical activity measurement in order to obtain the most accurate and comparable information.


What do patients want? Expectations and perceptions of IVF clinic information and support regarding frozen embryo disposition.
To describe frozen embryo holders' expectations and perceptions of IVF clinic information, support, and storage fees and their relevance to embryo disposition decision making. Qualitative interview study. Three northern California IVF practices. One hundred six families (110 women and 74 men) with an average of six frozen embryos in storage for 5 years. Three in-depth interviews over 1 year. Thematic analysis of interview transcripts. Although embryo holders expected that IVF clinics were under obligation to assist in the disposition decision and would be their main source of information, these expectations did not become manifest until years after embryo cryopreservation. Patients expressed a variety of preferences for the timing, format, and content of information and support, ranging from detailed written information to counselor/advocates that could provide logistical guidance and/or psychologic support. Embryo holders perceived an insufficiently defined infrastructure to facilitate donation to other couples, whereas donating to medical research was seen as less complicated and more likely to be encouraged and supported by physicians and clinics. Although increasing storage fees motivated disposition decision making, they could be interpreted as coercive and/or not reflective of actual clinic costs. Frozen embryo-holding patients' expectations of information and support to assist them with disposition decision making and embryo donation suggests that IVF clinics may benefit from a review of their frozen embryo counseling, storage, and disposition policies and procedures.


[Dynamic evaluation of the effects of quality management].
Evaluation of the effects of quality management over time at a radiology department. Data concerning the performance of the department, entered on a monthly basis, will be compared with entries in the error report system on the basis of time series analysis (regression models taking seasons and auto-correlation effects into account). The observation period consists of 46 homogeneous monthly time pulses. Effects of the suggestions and the total number of reports in the quality assurance system on the performance of the department can be observed with a two-month delay. This association is statistically highly significant (p < 0.01) and, because of the procedures used, not attributable to general developmental trends, seasonal fluctuations or autoregressive processes. Evaluation of quality assurance measures is a well justified demand and should be based on the analysis of data collected from quality assurance systems operating on a continuous basis over a long period of time. The analysis of data from a radiology department shows that quality assurance is reflected in the performance of the department.


The use of periodontal probes and radiographs in clinical trials of diagnostic tests.
Periodontal probing attachment level measurements and intraoral radiographs are used to assess the level of the clinical attachment and bone support in the diagnosis of periodontitis. Together these physical measurements of tooth support comprise the standard against which new diagnostic tests are compared. Since probing and radiographs provide a measure of the severity of attachment or bone loss at one point in time, serial measurements must be compared to determine whether periodontitis is progressive. Periodontal probing may be performed manually or by using controlled force electronic instruments. The resolution, depending on the instrument, will vary from 1.0 mm to 0.1 mm. Variations in probing force, size and shape of tip, location of tip placement, detection or reference landmarks for attachment level probing, degree of gingival inflammation, and transcription may adversely influence accuracy. Electronic probes offer the advantage of improved resolution, force control, and automatic recording, but the literature is inconsistent about the advantages in terms of repeatability and accuracy. Radiographic assessment of alveolar bone loss may be achieved by visual interpretation, measurement, or digital image analysis. While visual interpretation of unstandardized radiographs is insensitive to changes in bone, standardized radiographs can permit measurement of changes on the order of 0.2 mm when computerized methods are used. Newer techniques such as digital subtraction radiography permit detection of bony changes too small to be seen by the unaided eye and are over 95% sensitive and specific in detecting bony changes less than 10 mg.


[Infiltrating lobular carcinoma of the breast. Clinical picture, treatment and prognosis].
An analysis of 80 patients with infiltrating lobular carcinoma of the breast treated at Center of Oncology in Kraków is presented. All patients underwent radical mastectomy. The evaluation of treatment results showed stage, pathological tumor size, and involvement of axillary nodes as the prognostic factors. The ten-year survival rate NED in all group was 38.8%; for stage I, II, and III it was 62.5%, 48.8%, and 19.4% respectively.


Adaptation of the bacterial membrane to changing environments using aminoacylated phospholipids.
Fine-tuning of the biophysical properties of biological membranes is essential for adaptation of cells to changing environments. For instance, to lower the negative charge of the lipid bilayer, certain bacteria add lysine to phosphatidylglycerol (PG) converting the net negative charge of PG (-1) to a net positive charge in Lys-PG (+1). Reducing the net negative charge of the bacterial cell wall is a common strategy used by bacteria to resist cationic antimicrobial peptides (CAMPs) secreted by other microbes or produced by the innate immune system of a host organism. The article by Klein et al. in the current issue of Molecular Microbiology reports a new modification of the bacterial membrane, addition of alanine to PG, in Pseudomonas aeruginosa. In spite of the neutral charge of Ala-PG, this modified lipid was found to be linked to several resistance phenotypes in P. aeruginosa. For instance, Ala-PG increases resistance to two positively charged antibacterial agents, a beta-lactam and high concentrations of lactate. These findings shed light on the mechanisms by which bacteria fine-tune the properties of their cell membranes by adding various amino acids on the polar head group of phospholipids.


Comparison of the effects of cognitive behavioural therapy and inhalation sedation on child dental anxiety.
To compare the effectiveness of inhalation sedation with nitrous oxide/oxygen (N2O/O2) and cognitive behavioural therapy (CBT) in reducing dental anxiety in preschool children. Randomised controlled clinical trial. This study was conducted on 45 preschoolers with moderate to severe dental anxiety (determined by the Children's Fear Survey Schedule Dental Subscale), who required pulp treatment of at least one primary mandibular molar. Baseline anxiety and cooperation levels were determined using Venham Clinical Anxiety and Cooperation Scales (VCAS and VCCS) and Venham Picture Test (VPT) at the first dental visit (dental prophylaxis and fluoride treatment). Before the second dental visit (pulp treatment), the children were randomly assigned to one of three groups--1: control, 2: N(2)O/O(2) and 3: CBT. In group 1, the usual behaviour management techniques were used, in group 2, nitrous oxide/oxygen gas was used and in group 3, unrelated play, Benson's breathing and positive self-talk and modelling were used. Anxiety and cooperation levels were determined at three periods: injection, rubber dam placement and the application of a high-speed handpiece with VCAS and VCCS and VPT. Finally, anxiety and cooperation differences between the two dental visits were compared within the three groups. Chi square, ANOVA and Kruskal-Wallis and Mann-Whitney U tests were used. N(2)O/O(2) and CBT significantly resulted in lower anxiety and higher cooperation in the second visit (at all three periods) compared to the control, although there was no significant difference between these two treatment methods. Both test methods were effective in reducing dental anxiety in preschoolers. Considering the adverse effects and necessity of equipment and trained personnel when using nitrous oxide and oxygen inhalation sedation, cognitive behavioural therapy is preferable because of its better applicability.


One-bead-one-compound library of end-capped dipeptides and deconvolution by microflow NMR.
As part of our program to identify novel small molecules with interesting biological activity, we have designed and synthesized a library of end-capped dipeptides with an emphasis on compound diversity, complexity, and membrane permeability. An approximately 1500-member library was synthesized manually on large polystyrene beads using the mix-and-split method. The final compounds were cleaved into 384-well plates to generate individual stock solutions for input into high-throughput biological screens. Individual compounds were decoded using a combination of mass spectrometry and microflow NMR spectroscopy. In principle, this approach to deconvolution obviates the need for complicated binary encoding-decoding strategies for one-bead-one-compound libraries.


Progresses and Challenges of Composite Laminates in Thin-Walled Structures: A Systematic Review.
Most engineering technologies, gadgets, and systems have been developed around the use of sophisticated materials. Composite laminates have found widespread application in various significant and innovative industries, such as aviation, maritime transportation, automobiles, and civil engineering. Recent studies have revealed that composite materials are extensively utilized in automotive, undersea, and structural applications. Extensive efforts have been dedicated to exploring the structural components constructed from composite materials due to their importance in engineering. While composite materials offer certain advantages over their metallic counterparts, they also present analysts and designers with intricate and challenging issues. Hence, this Review aims to highlight noteworthy studies on composite materials and their engineering applications, specifically focusing on structural components. Furthermore, this Review includes a comprehensive summary of the application of composite laminates, accompanied by a critical analysis of the existing literature in this field. By presenting this information, the Review intends to provide a valuable resource and guideline for researchers interested in leveraging composite materials for engineering structures.


Intravenous iron dextran for severe refractory restless legs syndrome.
Reduced brain iron is strongly associated with restless legs syndrome (RLS). Oral iron supplements are commonly recommended for RLS but are largely ineffective due to poor absorption and poor tolerability at required doses. Intravenous iron dextran has been shown to increase brain iron content. Surprisingly only a few reports have ever presented data on the clinical effect of high dose intravenous iron for RLS. We retrospectively identified 25 subjects (age 53.2+/-11.9, 7 male) that received intravenous iron for RLS refractory to conventional treatments. We infused 1g of high molecular weight iron dextran over five hours. The age of RLS onset was 32.6+/-13.0 years and 15 subjects had a positive family history of RLS. Patients attempted 7.5+/-2.7 medications for RLS prior to iron therapy. Baseline ferritins ranged from 5 to 248 ng/ml (mean 43.5+/-58.0) and 20/25 had ferritins of less than 50. Two subjects did not complete their entire infusion due to anaphylactic type symptoms but are included. Overall, 2 subjects reported complete amelioration of all RLS symptoms, 11 reported marked improvement, 2 moderate improvement, 3 mild improvement, and 6 reported no improvement. For those with improvement, the duration of effect was highly variable (mean 15.8+/-17.7 weeks, range 1-60 weeks). Twelve subjects had multiple infusions. Iron dextran can dramatically improve refractory RLS but results are inconsistent and not predicted by patient demographics. Although burdened by a higher rate of anaphylactic reactions, iron dextran may be superior to other IV iron preparations.


Role of nitrogen additive and temperature on growth of diamond films from nanocrystalline to polycrystalline.
In this work, the coupled effect of nitrogen addition into CH4/H2 mixtures and surface temperature on diamond growth ranging from large grained polycrystalline to fine-grained nanocrystalline were investigated. Moreover a new growth parameter window for simultaneous growth of nanocrystalline diamond (NCD) and {100} textured large-grained diamond films was developed by using a high power high pressure 5 kW microwave plasma assisted chemical vapor deposition (MPCVD) reactor. Scanning electron microscope (SEM), Raman spectroscopy, and X-ray diffraction (XRD) are employed to characterize the morphology, crystalline quality and texture of the diamond samples. Our results can be grouped by two catalogs: First, deposition run without and with 0.24% N2 addition, while keeping all the other parameters constant, resulted in a high quality transparent large-grained polycrystalline diamond film and a NCD film, respectively. This result clearly evidences nitrogen induced nanocrystallinity. Then, two different substrate surface temperatures were obtained by overlapping a small silicon slice on the top centre of a large silicon wafer of 5.08 cm in diameter in only one deposition run using 0.24% N2 addition and the same set of parameters as the previous runs. From this growth run, a NCD film of growth rate around 2.3 microm/h was obtained at low temperature, while a {100} textured large-grained diamond film of much higher growth rate about 10.4 microm/h was grown at high temperature. These results not only confirm the reproducibility of NCD by N2 addition, but also indicate that distinct growth modes were involved at different substrate temperatures with 0.24% nitrogen addition, or coupled effect of nitrogen addition and temperature on the growth of CVD diamond films happened. Finite element method (FEM) analysis was employed to simulate the temperature gradient and distribution on these two samples, and based on this simulation and other simulation results in the literature, the growth mechanism is briefly discussed.


A case of Kabuki make-up syndrome with central diabetes insipidus and growth hormone neurosecretory dysfunction.
A case of a 6 year old boy with Kabuki make-up syndrome with central diabetes insipidus and growth hormone neurosecretory dysfunction is reported. Magnetic resonance imaging revealed abnormal findings of the pituitary gland and stalk. Good catch-up growth was obtained by treatment with growth hormone. These findings suggest that hypothalamic-pituitary dysfunction might be involved in Kabuki make-up syndrome.


A sudden death case from retropharyngeal abscess.
A sudden death case, a 21-year-old man, from retropharyngeal abscess is reported. It seemed to be caused by an injury in the posterior wall of the pharynx by an ingested foreign body. Because he had never consulted a doctor, it had grown large in several days and ruptured into the pharynx, and he died suddenly from airway obstruction by the inhaled pus.


Effect of interaction between outer membrane permeability and beta-lactamase production on resistance to beta-lactam agents in gram-negative bacteria.
The effect of the interaction of beta-lactamase production and outer membrane permeability on the bacterial resistance to beta-lactam antibiotics was investigated using the Escherichia coli K12 substrains, which have outer membrane mutation and produce TEM-type penicillinase. Experiments confirmed that the cefazolin concentrations in the periplasm of cells exposed to the MIC were restricted to 2.4-4.6 microM among the bacteria, even though the MICs for the bacterial strains were distributed from 13 microM to 1,726 microM. The drug concentrations in the periplasm could be calculated on the basis of parameters obtained experimentally, and the calculated values were in fair agreement with the experimental values. The effect of beta-lactamase activity (Vmax/Km) and the outer membrane barrier on the elevation of MICs was observed to be synergistic, and the contribution of beta-lactamase was more effectively expressed in the bacterial cells with higher outer membrane barrier.


[Estimating the biological effect of detrimental substances on E. coli with flow microcalorimetry. II. Studies using 3 antibiotics].
The influence of three antibiotics (Penicillin G, Oxtetracycline, Polymyxin B), which show different modes of action against gram-negative bacteria, is tested on the growth of liquid E. coli cultures in a flow microcalorimeter. The antibiotics were added during the logarithmic growth phase of the culture when a heat flux of 40 mu W/ml was approached. A supply vessel and a reaction vessel were used for establishing of the baseline and for performing the test, respectively. When testing Oxytetracycline and Polymyxin B the germ content in the nutrient broth was determined, additionally. Some measurements of the optical density of the nutrient broth were carried out parallel to the microcalorimetric investigation on the effect of Polymyxin B. As was to be expected, Penicillin G shows an influence on E. coli at concentrations of about 50 microgram/ml medium, only. An influence of Oxytetracycline on the heat production can be observed at concentrations between 0.3 and 0.6 microgram/ml. Polymyxin B acts on the power-time-curve at 0.025 microgram/ml. The minimum doses of Oxytetracycline and Polymyxin B found by the microcalorimetric technique are distinctly lower than those found by bacterial count and by measuring the optical density. Microcalorimetric results are achieved within 2 hours after adding the test substance to the bacterial culture. Flow microcalorimetry seems to be a promising tool for testing antibacterial drugs.


The metabolic analysis of psoriasis identifies the associated metabolites while providing computational models for the monitoring of the disease.
The majority of studies on psoriasis have focused on explaining the genetic background and its associations with the immune system's response. The aim of this study was to identify the low-molecular weight compounds contributing to the metabolomic profile of psoriasis and to provide computational models that help with the classification and monitoring of the severity of the disease. We compared the results from targeted and untargeted analyses of patients' serums with plaque psoriasis to controls. The main differences were found in the concentrations of acylcarnitines, phosphatidylcholines, amino acids, urea, phytol, and 1,11-undecanedicarboxylic acid. The data from the targeted analysis were used to build classification models for psoriasis. The results from this study provide an overview of the metabolomic serum profile of psoriasis along with promising statistical models for the monitoring of the disease.


Hyperbaric oxygen induces apoptosis via a mitochondrial mechanism.
During therapeutic hyperbaric oxygenation lymphocytes are exposed to high partial pressures of oxygen. This study aimed to analyze the mechanism of apoptosis induction by hyperbaric oxygen. For intervals of 0.5-4 h Jurkat-T-cells were exposed to ambient air or oxygen atmospheres at 1-3 absolute atmospheres. Apoptosis was analyzed by phosphatidylserine externalization, caspase-3 activation and DNA-fragmentation using flow cytometry. Apoptosis was already induced after 30 min of hyperbaric oxygenation (HBO, P < 0.05). The death receptor Fas was downregulated. Inhibition of caspase-9 but not caspase-8 blocked apoptosis induction by HBO. Hyperbaric oxygen caused a loss of mitochondrial membrane potential and caspase-9 induction. The mitochondrial pro-survival protein Bcl-2 was upregulated, and antagonizing Bcl-2 function potentiated apoptosis induction by HBO. In conclusion, a single exposure to hyperbaric oxygenation induces lymphocyte apoptosis by a mitochondrial and not a Fas-related mechanism. Regulation of Fas and Bcl-2 may be regarded as protective measures of the cell in response to hyperbaric oxygen.


beta-Lactamases are absent from Archaea (archaebacteria).
beta-Lactamases, enzymes that hydrolyze and inactive beta-lactam antibiotics, are of widespread occurrence in Bacteria and are related to the metabolism of bacterial cell wall murein. So far, no information exists on beta-lactamases in Archaea, a separate domain of prokaryotes with diverse types of unique cell wall polymers. Different mesophilic methanogenic and extremely halophilic Archaea containing methanochondroitin, pseudomurein, or S-layer protein or glycoprotein cell walls, were tested for beta-lactamase activity with the chromogenic beta-lactam nitrocefin as substrate. Also tested were representative microbial Eucarya from algae, yeasts, and protozoa. No beta-lactamase activity was detected in any of the archaeal and eukaryotic organisms. This supports the view that beta-lactamases are restricted to the domain of Bacteria.


Quantum anharmonic densities of states using the Wang-Landau method.
The Wang-Landau sampling method is adapted to the calculation of quantum densities of states for fully coupled anharmonic systems. The accuracy of the method is illustrated against exact counting for two molecules with separable oscillators, namely, the Zundel complex H(5)O(2) (+) and the Na(11) cluster. Application to the fully coupled naphthalene molecule (C(10)H(8)) reveals significant deviations in the finite temperature thermodynamical properties that are not captured by simple perturbation theory. There are no limitations in the size of the molecules that can be treated with this method.


Effects of ibuprofen and hypoxia on neutrophil apoptosis in neonates.
Ibuprofen is a cyclooxygenase inhibitor that is effective in treating patent ductus arteriosus in preterm infants. However, recent trials have suggested that it may increase the risk of developing necrotizing enterocolitis and chronic lung disease. Apoptosis of neutrophils is impaired in newborns, leading to reduced clearance of activated cells and possibly contributing to the susceptibility of infants to these inflammatory diseases. In the present studies, we investigated the hypothesis that ibuprofen reduces neonatal neutrophil apoptosis in the setting of hypoxia or lipopolysaccharide (LPS). Neutrophils and peripheral blood mononuclear cells were isolated from adult and cord blood and cultured in the presence or absence of ibuprofen (1.5 mM), hypoxia (<5% O2), and bacterial LPS (100 ng/ml). Apoptosis was quantified by measuring binding of FITC-Annexin V using flow cytometry. Cytokine concentrations in cell supernatants were measured by ELISA. After 24 h, 20% of adult and 14% of neonatal neutrophils were apoptotic. Apoptosis was reduced by hypoxia in both adult and neonatal cells. Ibuprofen further reduced neutrophil apoptosis, but only when the cells were cultured in the presence of mixed leukocytes. This suggests that the effects of ibuprofen on apoptosis are dependent on soluble products secreted by peripheral blood mononuclear cells. We found that production of tumor necrosis factor (TNF)-alpha by neonatal leukocytes was significantly increased by ibuprofen, and was further increased following exposure to ibuprofen in the presence of LPS and hypoxia. In contrast, production of macrophage inflammatory protein (MIP)-1alpha was not affected by treatment with ibuprofen, and ibuprofen blocked induction of this chemokine by LPS. We conclude that the net effect of ibuprofen on neutrophils is antiapoptotic, especially in the presence of hypoxia or LPS. This effect may be mediated, in part, by increased production of TNF-alpha by peripheral blood mononuclear cells. These data suggest that treatment of infants with ibuprofen, in the presence of infection and/or tissue hypoperfusion/hypoxia, may contribute to the development of inflammatory diseases.


Rectocutaneous fistulas.
This article reviews the etiology, diagnosis, and treatment of rectal perforation and rectocutaneous fistula in small animals. In addition, the literature regarding use of enterostomy in small animals is reviewed and comparative aspects of this procedure in humans and horses are presented. A case report of rectal perforation leading to rectocutaneous fistula formation and the use of colostomy in the management of the case is presented.


Cavitation of Langmuir monolayers.
Cavitation in liquid expanded and liquid condensed Langmuir monolayers induced by laser heating or microbubble coalescence is studied experimentally using fluorescence and Brewster angle microscopy. The kinetics of hole closure of two-dimensional (2D) gaseous cavitation bubbles exhibits a decelerated dynamics for cavities surrounded by a liquid expanded phase and an accelerated dynamics for cavities in a liquid condensed phase. Most of the cavities in liquid condensed phases possess a nonconvex shape and do not close. The results are compared with theoretical predictions derived for 2D cavitation of liquid monolayers of different surface shear viscosities, and for solid monolayers with diffusive flux of vacancies and interstitials. While part of the theory is in qualitative agreement with the experiment, the experimentally observed hole persistence within the liquid condensed phases and the hole closure within liquid expanded phases remains to be explained. The technique of microbubble coalescence might be particularly useful for the study of the rheological properties of hexatic phases.


Cyclosporin A inhibits caspase-independent death of NGF-deprived sympathetic neurons: a potential role for mitochondrial permeability transition.
Opening of the permeability transition pore (PTP) has been implicated as an important mitochondrial event that occurs during apoptosis. We examined the role of the PTP in the well-characterized cell death of rat sympathetic neurons deprived of nerve growth factor (NGF) in vitro. Removal of NGF causes these neurons to undergo either a classic apoptotic cell death or, when treated with a broad-spectrum caspase inhibitor such as boc-aspartyl(OMe)-fluoromethylketone (BAF), a delayed, nonapoptotic cell death. The PTP inhibitor, cyclosporin A (CsA), blocked commitment-to-die in the presence of BAF, as defined by the ability of NGF readdition to rescue cells, but had little effect on commitment-to-die in the absence of BAF. CsA did not have trophic effects on BAF-saved cells, but did block the decrease in mitochondrial membrane potential. These data suggest that PTP opening is a critical event in caspase-independent, nonapoptotic (but not caspase-dependent, apoptotic) death of NGF-deprived rat sympathetic neurons.


Honey bee protein atlas at organ-level resolution.
Genome sequencing has provided us with gene lists but cannot tell us where and how their encoded products work together to support life. Complex organisms rely on differential expression of subsets of genes/proteins in organs and tissues, and, in concert, evolved to their present state as they function together to improve an organism's overall reproductive fitness. Proteomics studies of individual organs help us understand their basic functions, but this reductionist approach misses the larger context of the whole organism. This problem could be circumvented if all the organs in an organism were comprehensively studied by the same methodology and analyzed together. Using honey bees (Apis mellifera L.) as a model system, we report here an initial whole proteome of a complex organism, measuring 29 different organ/tissue types among the three honey bee castes: queen, drone, and worker. The data reveal that, e.g., workers have a heightened capacity to deal with environmental toxins and queens have a far more robust pheromone detection system than their nestmates. The data also suggest that workers altruistically sacrifice not only their own reproductive capacity but also their immune potential in favor of their queen. Finally, organ-level resolution of protein expression offers a systematic insight into how organs may have developed.


Effects of cytosine hydroxymethylation on DNA strand separation.
Cytosine hydroxymethylation is an epigenetic control factor in higher organisms. New discoveries of the biological roles of hydroxymethylation serve to raise questions about how this epigenetic modification exerts its functions and how organisms discriminate cytosine hydroxymethylation from methylation. Here, we report investigations that reveal an effect of cytosine hydroxymethylation on mechanical properties of DNA under load. The findings are based on molecular force assay measurements and steered molecular dynamics simulations. Molecular force assay experiments identified significant effects of hydroxymethylation on stretching-induced strand separation; the underlying physical mechanism has been revealed by steered molecular dynamics simulations. We find that hydroxymethylation can either upregulate or downregulate DNA's strand separation propensity, suggesting that hydroxymethylation can control gene expression by facilitating or obstructing the action of transcription machinery or the access to chromosomal DNA.


Surgical treatment of atrial fibrillation.
Surgery aims to eliminate atrial fibrillation (AF) through direct modification of the arrhythmogenic substratum. The Maze procedure, developed two decades ago, has proven to be clearly effective in restoring sinus rhythm in AF patients with or without associated organic cardiac disorders. Indications for surgery may be tailored to the clinical situation involved. In patients with continuous AF associated with structural heart disease (eg, valvular, congenital or coronary artery disease), the performance of a concomitant AF ablation procedure proven to add minimal morbidity to the operation may be highly beneficial to patient outcome. It is likely, although not entirely proven, that the restoration and maintenance of sinus rhythm after mitral valve surgery promotes survival by preventing tachycardia-induced cardiomyopathy and stroke. Novel strategies for AF surgery involve the use of alternate energy sources to create the lines of block in the atria and the simplification of the lesion pattern compared with the earlier Cox-Maze procedure. Published clinical data support the contention that left atrial ablation techniques performed concomitantly with valvular and/or coronary artery bypass surgery are likely to result in a 70% to 90% cure rate of AF in patients with preoperatively documented AF. Despite the lack of evidence for long-term outcome benefit, intraoperative pulmonary vein ablation, feasible with minimal morbidity, clearly appears to be an improvement over simply ignoring AF in patients undergoing cardiac surgery. Left atrial appendectomy appears warranted in patients with chronic persistent AF.


Differential cell cycle and proliferation marker expression in ductal pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia (PanIN).
Pancreatic cancer is an aggressive tumour following a multistep progression model through precursors called pancreatic intraepithelial neoplasia (PanIN). Identification of reliable prognostic markers would help in improving survival. The aim of this study was to investigate the role as well as the prognostic significance of different cell cycle and proliferation markers, namely p21, p27, p53 and Ki-67, in pancreatic carcinogenesis. We analysed the expression of p21, p27, p53 and Ki-67, in 210 ductal pancreatic adenocarcinomas, 40 PanIN-3 cases and 40 normal controls combined in a tissue microarray. The results were correlated with clinicopathological and follow-up data. Our study revealed a differential p27, p21, p53, and Ki-67 expression between ductal adenocarcinoma, PanIN-3 and normal pancreas. p27 expression progressively decreased from normal pancreas to PanIN and to pancreatic cancer. Decreased p27 and increased p53 expression showed a significant association with the T stage. A Ki-67 >5% correlated with reduced survival. In pancreatic cancer, loss of p27 and increased p53 expression is associated with a more aggressive phenotype. p27 may play an important role in pancreatic carcinogenesis. A Ki-67 >5% independently predicted poor outcome.


Arsenic alters nitric oxide signaling similar to autism spectrum disorder and Alzheimer's disease-associated mutations.
Epidemiological studies have proven that exposure to Arsenic (AS) leads to the development of many neurological disorders. However, few studies have investigated its molecular mechanisms in the brain. Our previous work has revealed nitric oxide (NO)-mediated apoptosis and SNO reprogramming in the cortex following arsenic treatment, yet the role of NO and S-nitrosylation (SNO) in AS-mediated neurotoxicity has not been investigated. Therefore, we have conducted a multidisciplinary in-vivo study in mice with two different doses of Sodium Arsenite (SA) (0.1 ppm and 1 ppm) in drinking water. We used the novel SNOTRAP-based mass spectrometry method followed by the bioinformatics analysis, Western blot validation, and five different behavioral tests. Bioinformatics analysis of SA-treated mice showed significant SNO-enrichment of processes involved in mitochondrial respiratory function, endogenous antioxidant systems, transcriptional regulation, cytoskeleton maintenance, and regulation of apoptosis. Western blotting showed increased levels of cleaved PARP-1 and cleaved caspase-3 in SA-treated mice consistent with SA-induced apoptosis. Behavioral studies showed significant cognitive dysfunctions similar to those of Autism spectrum disorder (ASD) and Alzheimer's disease (AD). A comparative analysis of the SNO-proteome of SA-treated mice with two transgenic mouse strains, models of ASD and AD, showed molecular convergence of SA environmental neurotoxicity and the genetic mutations causing ASD and AD. This is the first study to show the effects of AS on SNO-signaling in the striatum and hippocampus and its effects on behavioral characteristics. Finally, further investigation of the NO-dependent mechanisms of AS-mediated neurotoxicity may reveal new drug targets for its prevention.


Hospital Compare drives hospital performance improvement initiatives.
On April 1, 2005, the impetus for public reporting of comparative hospital data was ratcheted up a giant notch by the Centers for Medicare and Medicaid Services and the Hospital Quality Alliance. Even before reaching the public's radar screen, Hospital Compare--a website that includes quality measures on how often large, acute-care and smaller, critical care hospitals provide recommended treatments that adults should receive for certain conditions--is having a major impact on hospital performance initiatives.


Making membranes green: construction and characterization of GFP-fusion proteins targeted to discrete plasma membrane domains.
Cell membranes contain glycolipid-enriched membrane (GEM) domains, or lipid rafts. GEM domains represent a discrete assembly ofproteins and lipids within the plasma membrane thatfunctions in cell signaling. However, studies of the GEM domains often include the disruption of cells with detergent. Thus, many of the physical and biological properties of GEM domains remain unknown and even controversial. An approach to study these domains but avoid detergent lysis is to measure their properties using the fluorescence imaging of live cells. Accordingly, GFP was targeted to either the GEM or the non-GEMfraction of the plasma membrane using the minimal membrane-anchoring signals of p56lck and pp60c-Src, respectively. The targeting of the fusion proteins to the respective membrane fractions was assayed by membrane fractionation and by quantitating the enrichment in GEM caps in stimulated T cells. The results show that the GEM marker was targeted to GEM domains with similar efficiency as other GEM-associated proteins. Conversely, the non-GEM marker was completely excluded from GEM domains. These constructs represent a useful toolfor studying the discrete fractions of the plasma membrane in live cells using fluorescence imaging.


[Free transplantation of the split skin graft].
On basis of treatment results analysis in 932 patients (1000 operations) with trophic ulcers and protractedly nonhealing wounds of lower limbs, caused by different reasons but for the most part by chronic lymphovenous insufficiency, it has been proved that use of autodermotransplatation in complex treatment allows to reduce the treatment terms, decrease the number of complications in early postoperative period and to improve the treatment results and the quality of patients life. Introduction of preoperative preparation program in practice, including modern original modes of treatment and wound management, efficacious technique of autodermotransplantant fixation on a graft using biotissue ultrasonic bonding and active postoperative regimen management, allowed to improve treatment results.


Caring for the newborn with an omphalocele.
An omphalocele, a ventral defect of the umbilical ring resulting in herniation of the abdominal viscera, is one of the most common congenital abdominal wall defects seen in the newborn. Omphaloceles occur in 1 in 3000 to 10,000 live births. Associated malformations such as chromosomal, cardiac, or genitourinary abnormalities are common. Postnatal management includes protection of the herniated viscera, maintenance of fluids and electrolytes, prevention of hypothermia, gastric decompression, prevention of sepsis, and maintenance of cardiorespiratory stability. A primary or staged closure approach may be used to repair the defect. Some giant omphaloceles require a skin flap or nonoperative management approach, hoxvever. Immediate postoperative complications, usually related to significant changes in intra-abdominal pressures, include compromise of interior venous blood return and hemodynamic and respiratory instability due to diaphragmaric elevation. Complications occur more frequently with giant defects. Potential short-term complications include necrotizing enterocolitis, prolonged ileus, and respiratory distress. Long-term complications include parenteral nutrition dependence, gastroesophageal reflux, parenteral nutrition-related liver disease, feeding intolerance, and neurodevelopmental delay. Overall, advances in surgical therapies and nursing care have improved outcomes for infants with omphaloceles; survival rates for those with isolated omphaloceles are reported at 75 to 95 percent. Infants with associated anomalies and giant omphaloceles have the poorest outcomes.


[Propionibacterium acnes adenitis].
Propionibacterium acnes is a gram-positive pleomorphic rod-shaped anaerobic saprophyte of the skin, mouth and upper respiratory tract. Although associated with acne vulgaris, it is otherwise reported as a human pathogen only rarely, in various infections, notably cutaneous and osteoarticular, and in endocarditis. We report here a case of bilateral P. acnes-abscessed adenitis of the inguinal folds. A 32 year-old man presented with inguinal lymph nodes that had progressively and bilaterally reddened and become painful, with fistulation of the skin and pus. Culture of a surgical sample identified P. acnes. Although this strain has been associated with lymph node granuloma, especially in sarcoidosis, abscessed lymph node infection as seen in our patient has never been reported.


Gated Silica Mesoporous Materials in Sensing Applications.
Silica mesoporous supports (SMSs) have a large specific surface area and volume and are particularly exciting vehicles for delivery applications. Such container-like structures can be loaded with numerous different chemical substances, such as drugs and reporters. Gated systems also contain addressable functions at openings of voids, and cargo delivery can be controlled on-command using chemical, biochemical or physical stimuli. Many of these gated SMSs have been applied for drug delivery. However, fewer examples of their use in sensing protocols have been reported. The approach of applying SMSs in sensing uses another concept-that of loading pores with a reporter and designing a capping mechanism that is selectively opened in the presence of a target analyte, which results in the delivery of the reporter. According to this concept, we provide herein a complete compilation of published examples of probes based on the use of capped SMSs for sensing. Examples for the detection of anions, cations, small molecules and biomolecules are provided. The diverse range of gated silica mesoporous materials presented here highlights their usefulness in recognition protocols.


Anisotropic diffusion-limited aggregation.
Using stochastic conformal mappings, we study the effects of anisotropic perturbations on diffusion-limited aggregation (DLA) in two dimensions. The harmonic measure of the growth probability for DLA can be conformally mapped onto a constant measure on a unit circle. Here we map m preferred directions for growth to a distribution on the unit circle, which is a periodic function with m peaks in [-pi,pi) such that the angular width sigma of the peak defines the "strength" of anisotropy kappa= sigma(-1) along any of the m chosen directions. The two parameters (m,kappa) map out a parameter space of perturbations that allows a continuous transition from DLA (for small enough kappa ) to m needlelike fingers as kappa--> infinity. We show that at fixed m the effective fractal dimension of the clusters D(m,kappa) obtained from mass-radius scaling decreases with increasing kappa from D(DLA) approximately 1.71 to a value bounded from below by D(min) = 3 / 2. Scaling arguments suggest a specific form for the dependence of the fractal dimension D(m,kappa) on kappa for large kappa which compares favorably with numerical results.


Marginal Discrepancies of Monolithic Zirconia Crowns: The Influence of Preparation Designs and Sintering Techniques.
The marginal fit is an essential component for the clinical success of prosthodontic restorations. The aim of this study was to investigate the influence of different abutment finish line widths and crown thicknesses on the marginal fit of zirconia crowns fabricated using either standard or fast sintering protocols. Six titanium abutments were fabricated for receiving zirconia molar crowns. Crowns were designed virtually and milled from partially sintered zirconia blanks and divided into 12 groups (n = 10/group). Crowns in groups 1 to 6 were sintered by standard sintering, while those in groups 7 to 12 were sintered by fast sintering. Groups were further categorized according to abutment finish line and crown thickness: G1/G7 (0.5 mm chamfer, 0.8 mm thick); G2/G8 (0.5 mm chamfer, 1.5 mm thick); G3/G9 (1.0 mm chamfer, 0.8 mm thick); G4/10 (1.0 mm chamfer, 1.5 mm thick); G5/G11 (1.2 mm chamfer, 0.8 mm thick); G6/G12 (1.2 mm chamfer, 1.5 mm thick). The marginal gaps were assessed at 8 locations using digital microscopy. The linear mixed effect model analysis was performed at a significance level of 0.05. All vertical marginal gaps were within the clinically acceptable range (∼11-52 μm). G8 (FS, 0.5 mm chamfer, 1.5 mm thick) demonstrated the largest gaps (47.95 μm, 95% CI: 44.57-51.23), whereas G3 (SS, 1.0 mm chamfer, 0.8 thick) had the smallest marginal gap (14.43 μm, 95% CI: 11.15-17.71). A linear mixed effect models showed significant differences for the interaction between finish line × crown thickness × sintering (F = 18.96, p < 0.001). The lingual surfaces showed the largest gaps in both sintering protocols, while the mesial and mesiobuccal surfaces demonstrated the smallest gaps. There was a significant interaction between finish line widths, crown thickness, and sintering protocol on the marginal gaps in both sintering protocols; 1.0 mm finish line preparations with either 0.8 mm or 1.5 mm occlusal reduction had better marginal fit in both sintering protocols compared to 0.5 mm or 1.2 mm finish lines. Smaller marginal discrepancies were observed for standard sintering crowns with a 0.5 mm finish line and 1.5 mm occlusal reduction. Conservative occlusal reduction should be accompanied with a 1.2 mm finish line to obtain better marginal fit for full-contoured zirconia crowns.


Effectiveness and safety of eribulin mesylate: a new therapeutic option in the treatment of metastatic breast cancer.
There is no standard third-line chemotherapy treatment option for patients with metastatic breast cancer who have received an anthracycline and/or a taxane. A recent Phase III randomized controlled trial compared a new agent, eribulin mesylate with physician's treatment of choice in heavily pretreated patients with metastatic breast cancer, and a survival advantage was observed. Eribulin is a non-taxane microtubule dynamics inhibitor, approved by the US Food and Drug Administration (FDA) in November 2010 for use in patients who previously received at least two prior lines of chemotherapy for metastatic breast cancer. The mechanism of action, pharmacokinetics and the efficacy and safety data from preclinical and clinical trials of this new agent are presented in this paper. Phase II and a recent Phase III trial indicate that eribulin is well tolerated with a predictable safety profile. The most frequent adverse events observed in patients receiving eribulin were asthenia/fatigue, neutropenia, alopecia, peripheral neuropathy and nausea. It represents a new treatment option in the setting of anthracycline and taxane-refractory metastatic breast cancer.


[History of orthopedics].
Functional Jaws Orthopedics has become of great importance and development, because of the evolution of orthodontics, not only treating dental malpositions but also referring these anomalies to the rest of the body, in an anatomic-functional whole.


Role of thoracic and abdominal tomography in identifying a potential source of infection in patients with acute fever of unknown focus.
The objective of this study was to evaluate the relationship between clinical features and the presence of infection on thoracic and abdominal tomography (CT) scans in emergency department (ED) patients with acute febrile illness without apparent source. Patients aged 18 years and over who presented to ED with acute fever of unknown origin between January 1, 2020 and December 31, 2020 and underwent CT imaging (thoracic and abdomen) as a diagnostic test were included in the study retrospectively. Acute fever of unknown origin was defined as the absence of a history or physical examination finding that could explain the possible cause of fever, normal values of parameters that would suggest an infection in the urine analysis, and absence of infiltration on chest X-ray. The patients were divided into two groups according to the presence and absence of a source of infection on CT. The clinical and demographic data of the patients were evaluated. The effect of clinical factors on the presence of infection in CT scans was determined using the logistic regression analysis. Among the 173 patients included in the study, the CT scans were positive for the source of infection in 31.2% (n = 54) and negative in 68.8% (n = 119). In the multiple logistic regression analysis, age ≥ 65 years [odds ratio (OR): 2.72, 95% confidence interval (CI):1.15-4.35, p < 0.001), presence of comorbidity (OR:2.37, 95%CI:1.08-4.14, p = 0.033), and procalcitonin positivity (PCT) (OR: 2.54, 95%CI: 1.29-4.95, p = 0.006) were identified as risk factors for the presence of infection in CT. Patient's age, presence of comorbidity and PCT level should be considered when deciding on the use of CT in determining the source of infection in acute febrile patients without clinical clues.


Utilization of a low-lactose milk.
This study was undertaken to determine if a milk containing prehydrolyzed lactose, yet affording full nutritional benefits, could be ingested by a milk intolerant (MI) population without the symptoms of lactose intolerance. MI was defined by the failure of serum glucose to rise greater than 20 mg/100 ml after ingestion of 50 gm of lactose as well as by subjective and objective symptoms and signs after consumption of both 12.5 gm of lactose in water and 250 ml of skim milk. Lactose tolerance (LT) was evidenced by both lack of symptoms and a concomitant rise in serum glucose of greater than 20 mg/100 ml after ingestion of 50 gm lactose in water. A series of four, two hr tolerance tests were given to 12 MI patients and 12 LT controls. The following solutions were employed: 12.5 gm lactose, 250 ml skim milk. 250 ml low-lactose skim milk, and 6 gm glucose plus 6 gm galactose. In the MI group, significant differences were apparent between the tolerance test utilizing skim milk and that using low-lactose skim milk; no such differences were observed in the LT group. These observations indicate that in the MI population the lactose in skim milk was poorly absorbed or tolerated, but after hydrolysis the low-lactose skim milk was well tolerated. A MI individual then, appears able to absorb the monosaccharides of the prehydrolyzed milk and can, furthermore, tolerate the low-lactose skim milk without suffering from symptoms normally associated with lactose intolerance.


New paradigms in the recognition and acute treatment of migraine.
It would be ideal if clinical decisions regarding acute migraine treatment could be made on the basis of three parameters: a critical appraisal of available scientific evidence, clinical experience (including knowledge of the individual patient and his/her attack characteristics), and, of course, patient preferences. Patients are likely to prefer agents that offer rapid relief, pain-free status within 2 hours, no recurrence or need for rescue medication, extended time to recurrence (if present), consistency of therapeutic effect over multiple attacks, oral administration. good tolerability, safety, and minimal drug interactions. Fortunately, a number of specific therapies now are available which place these objectives within the patient's reach. Ongoing barriers to optimal migraine care include underrecognition, underconsultation, undertreatment, restrictions imposed by insurance companies, and exaggerated concerns regarding the safety of the triptans. Overcoming these barriers is likely to prove a more important contribution to patient care than endeavoring to establish the relative merits of one triptan over another. We have described in detail a number of strategies for improving recognition and treatment of migraine. Many headache specialists now believe that recurrent episodes of disabling headache, with a stable pattern over years, should be viewed as migraine until proven otherwise. In the end, this may represent the most useful paradigm in the primary care setting, where time is of the essence. Studies to validate this approach are needed. Acute treatment intervention that is based on scientific evidence, clinical experience, and patients' needs and desires will provide better outcomes than those presently obtained. Preliminary evidence favors early intervention with oral triptans, and randomized, prospective, double-blind, placebo-controlled studies, ideally employing a crossover design, are required to confirm this. The US Consortium's evidence-based guidelines, the National Headache Foundation's standards of care, and the Canadian guidelines have applied the standards of scientific inquiry to the field of headache management and "translation" of these guidelines into practical instruments for clinicians through vehicles such as the Primary Care Network's Patient-Centered Strategies for Effective Management of Migraine should raise the general standard of care for patients with migraine. Last, but far from least, initiatives undertaken by the World Health Organization (WHO) will add credibility to the many layfolk and professionals who have struggled to present headache as a disabling disorder worthy of scientific investigation and aggressive medical management. The WHO states: "These common complaints impose a significant health burden ... Despite this, both the public and the majority of healthcare professionals tend to perceive headache as a minor or trivial complaint. As a result, the physical, emotional, social and economic burdens of headache are poorly acknowledged in comparison with those of other, less prevalent, neurologic disorders." Migraine is finally out of the closet.


Particulate metal bioaccessibility in physiological fluids and cell culture media: Toxicological perspectives.
According to the literature, tiny amounts of transition metals in airborne fine particles (PM2.5) may induce proinflammatory cell response through reactive oxygen species production. The solubility of particle-bound metals in physiological fluids, i.e. the metal bioaccessibility is driven by factors such as the solution chemical composition, the contact time with the particles, and the solid-to-liquid phase ratio (S/L). In this work, PM2.5-bound metal bioaccessibility was assessed in various physiological-like solutions including cell culture media in order to evidence the potential impact on normal human bronchial epithelial cells (NHBE) when studying the cytotoxicity and inflammatory responses of PM2.5 towards the target bronchial compartment. Different fluids (H2O, PBS, LHC-9 culture medium, Gamble and human respiratory mucus collected from COPD patients), various S/L conditions (from 1/6000 to 1/100,000) and exposure times (6, 24 and 72h) were tested on urban PM2.5 samples. In addition, metals' total, soluble and insoluble fractions from PM2.5 in LHC-9 were deposited on NHBE cells (BEAS-2B) to measure their cytotoxicity and inflammatory potential (i.e., G6PDH activity, secretion of IL-6 and IL-8). The bioaccessibility is solution-dependent. A higher salinity or organic content may increase or inhibit the bioaccessibiliy according to the element, as observed in the complex mucus matrix. Decreasing the S/L ratio also affect the bioaccessibility depending on the solution tested while the exposure time appears less critical. The LHC-9 culture medium appears to be a good physiological proxy as it induces metal bioaccessibilities close to the mucus values and is little affected by S/L ratios or exposure time. Only the insoluble fraction can be linked to the PM2.5-induced cytotoxicity. By contrast, both soluble and insoluble fractions can be related to the secretion of cytokines. The metal bioaccessibility in LHC-9 of the total, soluble, and insoluble fractions of the PM2.5 under study did not explain alone, the cytotoxicity nor the inflammatory response observed in BEAS-2B cells. These findings confirm the urgent need to perform further toxicological studies to better evaluate the synergistic effect of both bioaccessible particle-bound metals and organic species.


Polyphosphate ions encapsulated in oxothiomolybdate rings: synthesis, structure, and behavior in solution.
Cyclic oxothiomolybdates containing polyphosphate ions were prepared by simple reactions in aqueous medium of the corresponding polyphosphate ions and the cyclic precursor K(2)I(2)Mo(10)S(10)O(10)(OH)(10)(OH(2))(5).15H(2)O. K(5)[Cl(P(2)O(7)]Mo(12)S(12)O(12)(OH)(12)(H(2)O)(4)].22H(2)O (1) was isolated from concentrated chloride solution (2.5 mol.L(-1)). 1 reveals a remarkable complex containing two different substrates encapsulated in a dodecanuclear ring, a H-bonded Cl(-) ion, and a covalently bonded [P(2)O(7)] group. The chloride ion in 1 can be selectively removed for a monohydrogenophosphate group yielding K(6)[(HPO(4))(P(2)O(7))Mo(12)S(12)O(12)(OH)(12)(H(2)O)(2)].19H(2)O (2), a mixed species containing a [P(2)O(7)] and a [HPO(4)] group. The substitution is accompanied by a significant change of the ring, which adopts a "pear-shape" conformation. In the presence of triphosphate ion, the "heart-shaped" decanuclear ring Rb(3)[(H(2)P(3)O(10))Mo(10)S(10)O(10)(OH)(10)].17.5H(2)O (3) is formed containing a linear [P(3)O(10)] group intimately embedded in the inorganic cyclic host. The three compounds were structurally characterized by single-crystal X-ray diffraction. The behaviors of 1, 2, and 3 in solution were studied by (31)P NMR. Variable temperature experiments, supported by a two-dimensional COSY (31)P experiment, revealed that the supramolecular interaction existing between the chloride ion and the ring in solid 1 is maintained in solution. Nevertheless, 1 remains labile, and successive equilibria were evidenced and interpreted as an ion-pair association involving a halide ion (Cl, Br, or I), responsible for the conformational change of the [P(2)O(7)] group within the cavity. The influence of the nature of the halide guest (Cl(-), Br(-), and I(-)) on the successive equilibria was studied, and the thermodynamic constant related to the postulated equilibrium was determined. The stability of the supramolecular association decreases in the order Cl > Br > I. In solution, a phosphate exchange is observed for 2 while for 3 the absence of temperature dependence of the (31)P NMR spectrum confirms the conformation of the host-guest system is blocked. Elemental analysis and infrared characterizations are also supplied.


β-Hemolytic streptococcal throat carriage and tonsillopharyngitis: a cross-sectional prevalence study in Gabon, Central Africa.
Group A streptococcus (GAS) and possibly other β-hemolytic streptococci (BHS) account for a considerable morbidity and mortality burden in African populations; however, disproportionately little is known about the epidemiology of BHS in sub-Saharan Africa. This study assessed the prevalence of GAS, group G streptococcus (GGS) and group C streptococcus (GCS) carriage and tonsillopharyngitis in a Central African population. A prospective cross-sectional study was performed to assess the prevalence of and risk factors for BHS carrier status and tonsillopharyngitis in children and adults in Gabon. The overall BHS carrier prevalence was 135/1,005 (13.4%); carrier prevalence of GAS, GGS, and GCS was 58/1,005 (5.8%), 50/1,005 (5.0%), and 32/1,005 (3.2%), respectively. Streptococcal carriage was associated with school and pre-school age (adjusted OR 2.65, 95% CI 1.62-4.36, p = 0.0001 and 1.90, 95% CI 1.14-3.17, p = 0.0141, respectively). Participants residing in urban areas were less likely carriers (OR 0.52, p = 0.0001). The point-prevalence of BHS-positive tonsillopharyngitis was 1.0% (9/1,014) and 15.0% (6/40) in school children with sore throat. Non-GAS exceeded GAS throat carriage and tonsillopharyngitis suggesting a yet underestimated role of non-GAS streptococci in BHS diseases.


Variation in the human genome and the inherited basis of common disease.
The availability of a reference human genome sequence-an increasingly dense catalog-knowledge of common genetic variation, and new developments in technology present an unprecedented opportunity to systematically explore the genetic basis of complex human diseases such as cancer. An understanding of the common mutations that can cause distinct human cancers will be critical for identifying new targets for drug discovery, patient stratification for clinical trials, and analysis of drug response data to delineate classes of patients that respond to therapy. The genome structure of cancer can be investigated in several ways. Germline mutations can be investigated in large-scale, case-control, or family studies. Somatic alternations can be identified using state-of-the-art genomic technologies such as high-density oligonucleotide arrays and targeted resequencing. Combined, these approaches will lead to a better understanding of the cancer genome.


Effect of multivariate process instability on principal component analysis: a case study.
With the rising use of principal component analysis/partial least squares (PCA/PLS) in the process analytical technology (PAT) initiative of the pharmaceutical industry, it seems appropriate to view that approach from a statistical process control (SPC) perspective. The purpose of this study was to demonstrate the effect of process instability (ie, state of statistical out-of-control) on use of PCA/PLS. The demonstrated differences in results should encourage PCA/PLS users to incorporate SPC as an active part of their process analytical control (PAC) toolkit to check for stability prior to drawing conclusions based on PCA/PLS analysis.


I-gel saves the day: Bradycardia and apnea in a patient undergoing burr hole and evacuation for a subdural hematoma under scalp block.
Awake craniotomy is generally performed in scalped block, although it is safe, but this procedure can sometimes produce severe hemodynamic disturbances. Here, we reported a case of 32-year-old male, who came for burr hole and during the craniotomy performed under scalped block developed bradycardia and became apneic as manifested by the absence of ETCO2 and no chest excursions. An I-gel was inserted rather than intubating the patient and the case was managed very well and which showed the importance of supraglottic airway devices in our day to day practice.


Differential response to myocardial reperfusion injury in eNOS-deficient mice.
Two strains of endothelial nitric oxide synthase (eNOS)-deficient (-/-) mice have been developed that respond differently to myocardial ischemia-reperfusion (MI/R). We evaluated both strains of eNOS(-/-) mice in an in vivo model of MI/R. Harvard (Har) eNOS(-/-) mice (n = 12) experienced an 84% increase in myocardial necrosis compared with wild-type controls (P < 0.05). University of North Carolina (UNC) eNOS(-/-) (n = 10) exhibited a 52% reduction in myocardial injury versus wild-type controls (P < 0.05). PCR analysis of myocardial inducible NO synthase (iNOS) mRNA levels revealed a significant (P < 0.05) increase in the UNC eNOS(-/-) mice compared with wild-type mice, and there was no significant difference between the Har eNOS(-/-) and wild-type mice. UNC eNOS(-/-) mice treated with an iNOS inhibitor (1400W) exacerbated the extent of myocardial necrosis. When treated with 1400W, Har eNOS(-/-) did not exhibit a significant increase in myocardial necrosis. These data demonstrate that two distinct strains of eNOS(-/-) mice display opposite responses to MI/R. Although the protection seen in the UNC eNOS(-/-) mouse may result from compensatory increases in iNOS, other genes may be involved.


Cytokines involved in B-cell differentiation and their sites of action.
B cells originate from pluripotent hematopoietic stem cells and differentiate in the bone marrow into mature B cells. The differentiation of a stem cell into a mature B cell can be subdivided into five steps: early pro-B cells, late pro-B cell stage, pre-B cell stage, immature B cells, and mature B cells. Each differentiation step appears to be regulated by co-receptor and cytokines. The earliest B-cell progenitors are bound to the stromal cell surface by adhesive interactions through cell surface molecules to promote the binding of c-kit to stem cell factor (SCF). At the late pro-B cell stage, interleukin-7 (IL-7) induces proliferation and differentiation of pro-B cells to pre-B cells. Surface Ig-expressing mature B cells leave bone marrow and circulate into peripheral lymphoid organs in which they can be activated to proliferate and to differentiate into antibody-secreting cells by encountering antigens and "helper" T (TH) cells. TH cells activate B cells by their products, cytokines such as IL-4, IL-5, and IL-6, and membrane-bound stimulatory molecules including CD40 ligand. Each cytokine has pleiotropic activity on B cells and other cell types, and acts through a specific receptor. Abnormal expression of a cytokine receptor and aberrant signal transduction causes functional abnormality of B cells.


[Jejunostomy by Midle in patients with insufficiency of anastomotic sutures of upper parts of gastrointestinal tract].
Insufficiency of anastomosis is one of the main causes of peritonitis. Progressed cachexia due to great losses through intestinal fistulas in combination with peritonitis was the indication to jejunostoma creation. Jejunostomy by Middle in the treatment of postoperative peritonitis due to sutures insufficiency of upper anastomosis of gastrointestinal tract permits to optimize treatment: to realize adequate enteral nutrition, intestinal decompression, to return fistula's losses. Polyorganic insufficiency, number of repeated surgeries and volume of loss through fistulas influence results of the treatment. Respiratory distress-syndrome and errosive bleeding have the most prognostic significance among the syndromes of polyorganic insufficiency.


Binding of dinitrogen to an iron-sulfur-carbon site.
Nitrogenases are the enzymes by which certain microorganisms convert atmospheric dinitrogen (N2) to ammonia, thereby providing essential nitrogen atoms for higher organisms. The most common nitrogenases reduce atmospheric N2 at the FeMo cofactor, a sulfur-rich iron-molybdenum cluster (FeMoco). The central iron sites that are coordinated to sulfur and carbon atoms in FeMoco have been proposed to be the substrate binding sites, on the basis of kinetic and spectroscopic studies. In the resting state, the central iron sites each have bonds to three sulfur atoms and one carbon atom. Addition of electrons to the resting state causes the FeMoco to react with N2, but the geometry and bonding environment of N2-bound species remain unknown. Here we describe a synthetic complex with a sulfur-rich coordination sphere that, upon reduction, breaks an Fe-S bond and binds N2. The product is the first synthetic Fe-N2 complex in which iron has bonds to sulfur and carbon atoms, providing a model for N2 coordination in the FeMoco. Our results demonstrate that breaking an Fe-S bond is a chemically reasonable route to N2 binding in the FeMoco, and show structural and spectroscopic details for weakened N2 on a sulfur-rich iron site.


MAP kinase/estrogen receptor cross-talk enhances estrogen-mediated signaling and tumor growth but does not confer tamoxifen resistance.
The estrogen receptor alpha (ERalpha) signaling plays an essential role in breast cancer progression and endocrine therapy. Mitogen-activated protein kinase (MAPK/Erk1/2) has been implicated in ligand-independent activation of ER, resulting in the cross-talk between growth factor and ER mediated signaling. In this study, we examined the effect of the cross-talk on estradiol (E(2))-mediated signaling, tumor growth and its effect on anti-estrogen therapy. Our findings demonstrate that expression of constitutively activated mitogen activated kinase kinase (MEK1), an immediate upstream activator of MAPK in estrogen receptor positive MCF-7 breast cancer cells (MEK/MCF-7), showed an increase in ERalpha-driven transcriptional activation. In MEK/MCF-7 cells maximal transactivation levels were achieved in response to treatment with much lower E(2) concentrations (10(-10) M E(2)) when compared to MCF-7 control cells (10(-8) M E(2)). Furthermore, we have seen an increased association between ERalpha and its nuclear coactivators AIB1 or TIF-2, in MEK/MCF-7 cells relative to those seen in MCF-7 control cells. In addition, in vivo studies show that MEK/MCF-7 cell tumors are approximately threefold larger than those of MCF-7 cell, in the presence of E(2). Immunohistochemical staining demonstrates that progesterone receptor (PR) and pS2, two E(2)-regulated gene products, are significantly increased in MEK/MCF-7 cell tumors compared to those of MCF-7 control tumors, suggesting that activation of ERalpha by MAPK enhances the expression of E(2)-regulated genes and accelerates tumor growth. Remarkably, the antiestrogens tamoxifen and ICI 182,780, were shown both in vitro and in vivo studies to efficiently antagonize the stimulatory effects of E(2) on ER regulated transactivation and tumor growth in MEK/MCF-7 as well as MCF-7 cell lines. Taken together, these data suggest that MAPK/ER cross-talk enhances ERalpha-mediated signaling and accelerates E(2)-dependent tumor growth without diminishing sensitivity to the inhibitory effects of anti-estrogens.


Inhibition of IL-8-mediated MAPK activation in human neutrophils by beta1 integrin ligands.
Chemokine and integrin receptors must work in concert when circulating leukocytes mobilize toward a site of tissue inflammation or infection. In a previous study, we reported that ligation of the alpha5beta1 integrin with a 120-kDa cell-binding fibronectin fragment (120-kDa FN) in suspensions of human polymorphonuclear leukocytes (PMNLs) inhibited chemotaxis toward the chemokine called interleukin-8 (IL-8). Binding of chemokines to their receptors on leukocytes leads to the activation of heterotrimeric G proteins that initiate multiple signaling cascades, including p38 and p42/p44 mitogen-activated protein kinase (MAPK) pathways. In the present study, we examine the potential interaction of beta1 integrin ligation on chemokine-mediated MAPK signaling in human PMNLs. We demonstrate that blockade of the p42/p44 MAPK signaling pathway by the inhibitor PD98059 suppresses IL-8-mediated PMNL chemotaxis. Furthermore, when PMNLs are pretreated with 120-kDa FN or an activating antibody to beta1 integrins (TS2/16), IL-8-mediated phosphorylation of p42/p44 MAPK is also inhibited. In contrast, pretreating PMNL with a specific ligand (laminin-1) for the alpha6beta1 integrin does not suppress IL-8-mediated phosphorylation of p42/p44 MAPK. These observations demonstrate a desensitization of IL-8-mediated p42/p44 MAPK signaling in response to ligation of the alpha5beta1 integrin in PMNL. Also, they suggest an interplay between integrin and chemokine signaling during PMNL migration through the extracellular matrix.


The production of soluble and cellular interleukin-2 receptors by cord blood mononuclear cells following in vitro activation.
Cord blood mononuclear cells (CBMC) were investigated for their capacity to generate both cellular and soluble, supernatant interleukin-2 receptors (IL-2R) following cellular activation in vitro. Soluble IL-2R were measured in cell-free supernatants and in detergent-solubilized cell extracts with a "sandwich" enzyme-linked immunosorbent assay. CBMC and adult peripheral blood mononuclear cells were activated with phytohemagglutinin or the murine monoclonal antibody OKT3. CBMC and adult peripheral blood mononuclear cells generated cellular and soluble IL-2R in response to both activators. Peak values for supernatant IL-2R were observed on day 7, while peak values of cell-associated IL-2R occurred on day 5, followed by a decline on day 7. With the exception of supernatant IL-2R production induced by OKT3 stimulation, CBMC produced IL-2R in amounts comparable to adult mononuclear cells. Cord blood plasma also contained amounts of IL-2R comparable to that found in adult sera/plasma. Thus, CBMC appear largely immunocompetent with regard to the expression of IL-2R.


[NOS-2 induction in rat lungs after Escherichia coli lupopolisaccharide administration].
Endotoxin-induced acute lung injury may be differently modulated by nitric oxide, dependently on the phase of endotoxemia as well as on the amounts and cellular source of this free radical. We investigated rapid (within 1 hr) increase of NOS-2 mRNA and activity in rat lungs following endotoxin treatment. The increase of lung NOS-2 correlated with LPS-induced pulmonary neutrophil sequestration. Sequestrated leukocytes seem to be responsible for rapid NOS-2 induction in lung tissue after LPS treatment. The pathophysiological role of this phenomenon requires further clarification.


A rapid and simple one step method for isolation of poly(A)+ RNA from cells in monolayer.
A simple method was developed to isolate low abundance hormone receptor poly(A)+ RNA from cells in tissue culture. Adherent cells in tissue culture plates were directly released with proteinase K and solubilized in SDS. Oligo(dT) cellulose was directly added to the lysate to obtain poly(A)+ RNA. Yields and purity of the poly(A)+ RNA were comparable to other more lengthy methods. IGF-I receptor and insulin receptor mRNA could be detected on Northern blot without any degradation.


Immigrant women's perceptions of their maternity care: a review of the literature. Part 2.
In the first of this two part article, the methods of the literature review looking at immigrant women's perceptions of their maternity were outlined along with the first two themes identified, including communication and impediments to access of maternity care. In this concluding part, the remaining three themes of the literature review will be discussed and conclusions will be drawn, with recommendations for practice.


Dual regulation of actin rearrangement through lysophosphatidic acid receptor in neuroblast cell lines: actin depolymerization by Ca(2+)-alpha-actinin and polymerization by rho.
Lysophosphatidic acid (LPA) is a potent lipid mediator with actions on many cell types. Morphological changes involving actin polymerization are mediated by at least two cognate G protein-coupled receptors, LPA(1)/EDG-2 or LPA(2)/EDG-4. Herein, we show that LPA can also induce actin depolymerization preceding actin polymerization within single TR mouse immortalized neuroblasts. Actin depolymerization resulted in immediate loss of membrane ruffling, whereas actin polymerization resulted in process retraction. Each pathway was found to be independent: depolymerization mediated by intracellular calcium mobilization, and alpha-actinin activity and polymerization mediated by the activation of the small Rho GTPase. alpha-Actinin-mediated depolymerization seems to be involved in growth cone collapse of primary neurons, indicating a physiological significance of LPA-induced actin depolymerization. Further evidence for dual regulation of actin rearrangement was found by heterologous retroviral transduction of either lpa(1) or lpa(2) in B103 cells that neither express LPA receptors nor respond to LPA, to confer both forms of LPA-induced actin rearrangements. These results suggest that diverging intracellular signals from a single type of LPA receptor could regulate actin depolymerization, as well as polymerization, within a single cell. This dual actin rearrangement may play a novel, important role in regulation of the neuronal morphology and motility during brain development.


Distinct cytoplasmic regions of the growth hormone receptor are required for activation of JAK2, mitogen-activated protein kinase, and transcription.
The GH receptor (GHR) is a member of the cytokine/hematopoietic growth factor family, and protein tyrosine phosphorylation has been implicated in the signaling cascade of these receptors. It was recently shown that the tyrosine kinase JAK2 is associated with the GHR. GH induces the activation of JAK2, which phosphorylates itself and the receptor. Mitogen-activated protein (MAP) kinase activation and transcriptional stimulation of specific genes, such as Spi 2.1, have also been reported to be induced by GH. To identify functionally important regions in the cytoplasmic domain of the GHR, we compared the actions of the wild-type receptor, two truncated mutants, and one internal deletion mutant (similar to the intermediate Nb2 form of the PRL receptor) in transfectants of the Chinese hamster ovary cell line. A region of 46 amino acids adjacent to the membrane was found to be sufficient for activation of both JAK2 and MAP kinases. This region contains a proline-rich sequence (box 1) conserved in the cytokine receptor family that is important for signal transduction. For transcriptional activity, the C-terminal region of the GHR is required, and we found that the last 80 terminal residues contain sequences allowing activation of the Spi 2.1 promoter. Tyrosine phosphorylation of the receptor also requires the C-terminal portion of the GHR cytoplasmic domain, and we found that GHR tyrosine phosphorylation appears to be linked to activation of the Spi 2.1 transcription pathway. Thus, the GHR could be composed of at least 2 functional regions: the 46 proximal amino acids required for activation of JAK2 and sufficient to stimulate the MAP kinase pathway, and an additional carboxy-terminal region necessary for transcriptional activation.


Antioxidative system in sweet potato root is activated by low-temperature storage.
Sweet potato is susceptible to chilling injury during low-temperature storage. To explore the correlation between chilling injury and reactive oxygen species (ROS) metabolism, the content of ROS and the activities and gene expression of antioxidant enzymes were analyzed in the typical storage-tolerant cultivar Xushu 32 and storage-sensitive cultivar Yanshu 25. The activities of antioxidant enzymes including ascorbate peroxidase (APX), superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) were enhanced rapidly in the early period of storage in response to chilling stress. Thereafter, the content of ROS metabolites increased consistently due to gradual decrease in ROS scavenging enzymes. Storage-tolerant cultivar Xushu 32 had higher antioxidant enzyme activities and gene expressions as well as higher content of antioxidant metabolites and lower content of ROS metabolites compared with storage-sensitive cultivar Yanshu 25, suggesting that the capacity of ROS scavenging by antioxidant enzymes and antioxidants is highly associated with the tolerance of sweet potato to chilling stress. These results indicated that the antioxidative system is activated in the storage root of sweet potato and the antioxidative capacity is positively associated with better storage performance in the storage-tolerant cultivar. © 2019 Society of Chemical Industry.


Separation of splicing factor SF3 into two components and purification of SF3a activity.
Components required for the splicing of nuclear messenger RNA precursors in vitro have been isolated from HeLa cells. Here we describe the separation of splicing factor SF3 into two components, SF3a and SF3b. Both activities are required together with several other protein factors and U1 and U2 small nuclear ribonucleoproteins for the assembly of a presplicing complex which represents the first ATP-dependent step in the assembly of the active spliceosome. SF3a has been purified to homogeneity by a combination of ion-exchange chromatography, gel filtration, and glycerol gradient sedimentation. It consists of a complex of three polypeptides of 60, 66, and 120 kDa. The association of SF3a activity with these polypeptides has been confirmed by immunoprecipitation and depletion experiments using a monoclonal antibody directed against the 66-kDa subunit.


Effectiveness of an educational approach between adolescents and adults with patellofemoral pain syndrome: a scoping review with meta-analysis.
[Purpose] This study aimed to compare the effectiveness of an educational approach between adolescents and adults with patellofemoral pain syndrome. [Participants and Methods] The PROSPERO protocol number is CRD42022362680. Four databases (PubMed, CINAHL, Scopus, Cochrane) were searched. Randomized control trials on the effectiveness of the educational approach for patellofemoral pain syndrome were compared between adolescents and adults. Two investigators independently screened eligible studies. Two randomized control trials proceeded through meta-analysis with a visual analogue scale in the mid-term (from 18 weeks to 6 months). [Results] The meta-analysis results indicated that no significant difference was observed between education and combined education with exercise. A tendency to improve in the intervention of combined education with exercise for adolescents was noted, whereas no effect of education for adults was observed. [Conclusion] Treatment strategies combining education with exercise for patellofemoral pain syndrome may differ between adolescents and adults.


Understanding the binding affinity of noscapines with protease of SARS-CoV-2 for COVID-19 using MD simulations at different temperatures.
The current outbreak of a novel coronavirus, named as SARS-CoV-2 causing COVID-19 occurred in 2019, is in dire need of finding potential therapeutic agents. Recently, ongoing viral epidemic due to coronavirus (SARS-CoV-2) primarily affected mainland China that now threatened to spread to populations in most countries of the world. In spite of this, there is currently no antiviral drug/ vaccine available against coronavirus infection, COVID-19. In the present study, computer-aided drug design-based screening to find out promising inhibitors against the coronavirus (SARS-CoV-2) leads to infection, COVID-19. The lead therapeutic molecule was investigated through docking and molecular dynamics simulations. In this, binding affinity of noscapines(23B)-protease of SARS-CoV-2 complex was evaluated through MD simulations at different temperatures. Our research group has established that noscapine is a chemotherapeutic agent for the treatment of drug resistant cancers; however, noscapine was also being used as anti-malarial, anti-stroke and cough-suppressant. This study suggests for the first time that noscapine exerts its antiviral effects by inhibiting viral protein synthesis.


Scalp psoriasis.
Many people suffer from scalp psoriasis. While the cause of this condition is not known, there is effective treatment. With well-planned therapy and patient compliance, scalp lesions can be controlled. Useful agents include coal tar shampoos and preparations, keratolytics and topical corticosteroids. Systemic agents are almost never indicated for scalp psoriasis alone.


Early Trauma and Relationships among Recent Stress, Depressive Symptoms, Anxiety Symptoms, and Suicidal Ideation in Korean Women.
Evidence continues to accumulate that the presence or absence of early trauma (ET) implies unique characteristics in the relationships between suicidal ideation and its risk factors. We examined the relationships among recent stress, depressive symptoms, anxiety symptoms, and suicidal ideation in Korean suicidal women with or without such a history. Using data on suicidal adult females, 217 victims and 134 non-victims of ET, from the Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior, we performed structural equation modeling to investigate the contribution of recent stress, depressive symptoms, and anxiety symptoms on suicidal ideation within each group according to the presence or absence of a history of ET. Structural equation modeling with anxiety and depressive symptoms as potential mediators showed a good fit. Recent stress had a direct effect on both depressive symptoms and anxiety symptoms in both groups. Only anxiety symptoms for victims of ET (standardized regression weight, 0.281; P = 0.005) and depressive symptoms for non-victims of ET (standardized regression weight, 0.326; P = 0.003) were full mediators that increased suicidal ideation. Thus, stress contributed to suicidal ideation by increasing the level of anxiety and depressive symptoms for victims and non-victims, respectively. Tailored strategies to reduce suicidal ideation should be implemented according to group type, victims or non-victims of ET. Beyond educating suicidal women in stress-management techniques, it would be effective to decrease anxiety symptoms for those with a history of ET and decrease depressive symptoms for those without such a history.


Anesthetic technic using profound hypothermia for correction of congenital heart defects in infants and small children.
Profound hypothermia can be a useful adjunct in the intraoperative management of infants and small children undergoing surgical correction of congenital heart defects. A case description of a 5 1/2-month-old male infant with total anomalous pulmonary venous drainage who had successful repair using surface cooling, cardiopulmonary bypass, and pump cooling to 20 C with intermittent periods of low systemic blood flow illustrates the technic. Discussed are the value of surface cooling before cooling on cardiopulmonary bypass, physiologic changes affecting the intraoperative and postoperative course, and the major risks and advantages of the technic.


Case of intraoperative acute pulmonary embolism diagnosed by transesophageal echocardiography under general anesthesia and successfully managed with extracorporeal membrane oxygenation.
Acute pulmonary thromboembolism (PTE), which carries a high mortality rate, is difficult to diagnose when it occurs intraoperatively. Therefore, patient prognosis depends on a prompt diagnosis by anesthesiologists. A 49-year-old woman underwent right lower extremity dissection due to a contusion of the right lower extremity caused by trauma. Eleven days after surgery, she underwent debridement for necrosis of the amputation wound. Intraoperatively, a drop in blood pressure and tachycardia were observed, and PTE was suspected based on a rapid deterioration in oxygen saturation and a drop in end-tidal carbon dioxide partial pressure. Transesophageal echocardiography (TEE) showed a thrombus filling the right pulmonary artery, and a diagnosis of PTE was made. The patient was treated using venoarterial extracorporeal membrane oxygenation, and thrombectomy was performed the next day to save her life. In this case, we were able to diagnose and treat the intraoperative acute PTE at an early stage. In addition, the appropriate choice of treatment saved the patient's life without complications.


Sonic Hedgehog influences the balance of osteogenesis and adipogenesis in mouse adipose-derived stromal cells.
Adipose-derived stromal cells (ASCs) present a great potential for tissue engineering, as they are capable of differentiating into osteogenic and adipogenic cell types, among others. In this study, we examined the role of Hedgehog signaling in the balance of osteogenic and adipogenic differentiation in mouse ASCs. Results showed that Hedgehog signaling increased during early osteogenic differentiation (Shh, Ptc1, and Gli1), but decreased during adipogenic differentiation. N-terminal Sonic Hedgehog (Shh-N) significantly increased in vitro osteogenic differentiation in mouse ASCs, by all markers examined (*p < 0.01). Concomitantly, Shh-N abrogated adipogenic differentiation, by all markers examined (*p < 0.01). Conversely, blockade of endogenous Hedgehog signaling, with the Hedgehog antagonist cyclopamine, enhanced adipogenesis at the expense of osteogenesis. We next translated these results to a mouse model of appendicular skeletal regeneration. Using quantitative real-time polymerase chain reaction and in situ hybridization, we found that skeletal injury (a monocortical 1 mm defect in the tibia) results in a localized increase in Hedgehog signaling. Moreover, grafting of ASCs treated with Shh-N resulted in significantly increased bone regeneration within the defect site. In conclusion, Hedgehog signaling enhances the osteogenic differentiation of mouse ASCs, at the expense of adipogenesis. These data suggest that Hedgehog signaling directs the lineage differentiation of mesodermal stem cells and represents a promising strategy for skeletal tissue regeneration.


Pattern Formation in Phase-Separated Langmuir and Langmuir Monolayer Films.
Mixed monolayer films comprising hydrogenated and fluorinated surfactants can undergo phase separation to produce interfaces with diverse structures at the micrometer and nanometer scales. This review discusses our progress over the past decade to probe the relationship that exists between the molecular structure of the surfactants that comprise the films and the overall patterns formed in the monolayers. We review two main classes of mixed perfluorocarbon-hydrocarbon surfactant systems, including fatty acids and a recently developed family of EDTA-based gemini surfactants. In addition to summarizing the state-of-the-art of this field, the key scientific questions and relationships that require further elucidation are discussed, along with directions for continuing research into this fascinating area of research.


[Morbidity and mortality in a series of patients suffering from intraperitoneal neoplasia treated with peritoneal cytoreduction and hyperthermic intraperitoneal chemotherapy at the Fundación Santa Fe de Bogotá Teaching Hospital (ONCOLGroup--ATIA study)].
The procedure of radical peritonectomy followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is considered the standard treatment for peritoneal cancers. To evaluate various outcomes in a cohort of patients with peritoneal tumors treated with HIPEC. Twenty-four patients consecutively treated with radical peritonectomy plus HIPEC within the time frame of November 2007 to July 2010 were enrolled; 15 (62%) had tumors of appendicular origin, 4 (16.7%) had primary peritoneal tumors, 2 had ovarian carcinomas and there was one case of colon cancer, one carcinosarcoma and one hemangioendothelioma. Mean age was 53 years (range: 26-68) and median follow-up was 14.2 months (range: 1-32). Demographic data, histology, peritoneal cancer index (PCI), surgical procedure characteristics, recurrence-free survival (RFS), and overall survival (OS) were all evaluated. Short-term morbidity and mortality were also determined. Complete cytoreduction was achieved in 18 patients (75%). Mean PCI was 15 (<10: 41% and >10: 58%), and the median (range) for surgery duration, length of stay in the Intensive Care Unit, parenteral nutritional support, and hospital stay were 12,5 (7-20) hours, 11,4 (2-74) days, 13,8 (12-65) days, and 29,1 (10-90) days, respectively. One patient (4%) died 6 months after the procedure, due to multiple associated complications. Considerable morbidity was seen in 52% of cases, including thromboembolic events (41%), catheter-related bacteremia (29%), fistulas (29%), and nephrotoxicity (25%). Six patients (25%) recurred after a median of 21 months of RFS. Cytoreductive surgery plus HIPEC in well-selected patients presenting with tumors that affect the peritoneum is a procedure that can be carried out in Colombia with an adequate safety and effectiveness profile. Mortality was similar to that reported in the international literature.


Clinical applications of ultra-high field magnetic resonance imaging in multiple sclerosis.
Magnetic resonance imaging (MRI) is of paramount importance for the early diagnosis of multiple sclerosis (MS) and MRI findings are part of the MS diagnostic criteria. There is a growing interest in the use of ultra-high-field strength -7 Tesla- (7T) MRI to investigate, in vivo, the pathological substrate of the disease. Areas covered: An overview of 7T MRI applications in MS focusing on increased sensitivity for lesion detection, specificity of the central vein sign and better understanding of MS pathophysiology. Implications for disease diagnosis, monitoring and treatment planning are discussed. Expert commentary: 7T MRI provides increased signal-to-noise and contrast-to-noise-ratio that allow higher spatial resolution and better detection of anatomical and pathological features. The high spatial resolution reachable at 7T has been a game changer for neuroimaging applications not only in MS but also in epilepsy, brain tumors, dementia, and neuro-psychiatric disorders. Furthermore, the first 7T device has recently been cleared for clinical use by the food and drug administration.


Energy-entropy prediction of octanol-water logP of SAMPL7 N-acyl sulfonamide bioisosters.
Partition coefficients quantify a molecule's distribution between two immiscible liquid phases. While there are many methods to compute them, there is not yet a method based on the free energy of each system in terms of energy and entropy, where entropy depends on the probability distribution of all quantum states of the system. Here we test a method in this class called Energy Entropy Multiscale Cell Correlation (EE-MCC) for the calculation of octanol-water logP values for 22 N-acyl sulfonamides in the SAMPL7 Physical Properties Challenge (Statistical Assessment of the Modelling of Proteins and Ligands). EE-MCC logP values have a mean error of 1.8 logP units versus experiment and a standard error of the mean of 1.0 logP units for three separate calculations. These errors are primarily due to getting sufficiently converged energies to give accurate differences of large numbers, particularly for the large-molecule solvent octanol. However, this is also an issue for entropy, and approximations in the force field and MCC theory also contribute to the error. Unique to MCC is that it explains the entropy contributions over all the degrees of freedom of all molecules in the system. A gain in orientational entropy of water is the main favourable entropic contribution, supported by small gains in solute vibrational and orientational entropy but offset by unfavourable changes in the orientational entropy of octanol, the vibrational entropy of both solvents, and the positional and conformational entropy of the solute.


OPTICAL COHERENCE TOMOGRAPHY BIOMARKERS TO DISTINGUISH DIABETIC MACULAR EDEMA FROM PSEUDOPHAKIC CYSTOID MACULAR EDEMA USING MACHINE LEARNING ALGORITHMS.
In diabetic patients presenting with macular edema (ME) shortly after cataract surgery, identifying the underlying pathology can be challenging and influence management. Our aim was to develop a simple clinical classifier able to confirm a diabetic etiology using few spectral domain optical coherence tomography parameters. We analyzed spectral domain optical coherence tomography data of 153 patients with either pseudophakic cystoid ME (n = 57), diabetic ME (n = 86), or "mixed" (n = 10). We used advanced machine learning algorithms to develop a predictive classifier using the smallest number of parameters. Most differentiating were the existence of hard exudates, hyperreflective foci, subretinal fluid, ME pattern, and the location of cysts within retinal layers. Using only 3 to 6 spectral domain optical coherence tomography parameters, we achieved a sensitivity of 94% to 98%, specificity of 94% to 95%, and an area under the curve of 0.937 to 0.987 (depending on the method) for confirming a diabetic etiology. A simple decision flowchart achieved a sensitivity of 96%, a specificity of 95%, and an area under the curve of 0.937. Confirming a diabetic etiology for edema in cases with uncertainty between diabetic cystoid ME and pseudophakic ME was possible using few spectral domain optical coherence tomography parameters with high accuracy. We propose a clinical decision flowchart for cases with uncertainty, which may support the decision for intravitreal injections rather than topical treatment.


Automated Phenotyping Indicates Pupal Size in Drosophila Is a Highly Heritable Trait with an Apparent Polygenic Basis.
The intense focus on studying human height has done more than any other genetic analysis to advance our understanding of the heritability of highly complex phenotypes. Here, we describe in detail the properties of a previously unexplored trait in Drosophila melanogaster that shares many salient properties with human height. The total length of the pupal case varies between 2.8 and 3.9 mm among natural variants, and we report that it is among the most heritable traits reported in this species. We have developed a simple semiautomatic phenotyping system with which a single operator can reliably score >5000 individuals in a day. The precision of the automated system is 0.042 mm (± 0.030 SD). All phenotyped individuals are available to be mated in subsequent generations or uniquely archived for future molecular work. We report both broad sense and narrow sense heritability estimates for two biologically distinct data sets. Narrow sense heritability (h2) ranged from 0.44 to 0.50, and broad sense heritability (H2) ranged from 0.58 to 0.61. We present results for mapping the trait in 195 recombinant inbred lines, which suggests that there are no loci with >10% effect size in this panel. We propose that pupal size genetics in Drosophila could represent a model complex trait amenable to deep genetic dissection using the automated system described.


Effects of immunization of heifers against estradiol on growth, reproductive traits, and carcass characteristics.
An experiment was performed to evaluate the effects of active immunization of heifers against estradiol on feedlot performance (growth and efficiency), carcass characteristics, and reproductive functions. Seventy-two crossbred heifers were divided into four equal treatment groups consisting of controls, ovariectomized heifers, and heifers actively immunized against keyhole limpet-estradiol antigen and bovine serum albumin-estradiol antigen. Heifers were fed ad libitum for 170 days. Both groups of heifers immunized against estradiol had higher (P less than 0.05) average daily gains than controls. Heifers immunized against bovine serum albumin-estradiol had increased feed efficiency (P less than 0.05) over controls. Ovariectomized heifers did not perform at levels sufficient to compensate for the initial setback from surgery. No differences were noted in carcass grade, quality, or concentration of water, fat, or protein. Uterine weights were increased in estrogen-immunized animals but were not significantly greater than controls. Ovarian weights and numbers of large follicles (greater than 9 mm diam) in immunized animals were significantly greater than in controls. Twenty-eight percent of the animals (n = 5) in the bovine serum albumin-estradiol-immunized group had cystic follicles (greater than 20 mm diam) and 50% (n = 9) of this group had no detectable corpus luteum. Low titer (1:100) systemic binding of estrogens may act as a steroid reservoir in which systemic estrogen clearance is decreased and availability to target tissues is increased.