A comparison of postengraftment infectious morbidity and mortality after allogeneic partially T cell-depleted peripheral blood progenitor cell transplantation versus T cell-depleted bone marrow transplantation.
Postengraftment infections are a major cause of transplant-related morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-SCT). Allogeneic peripheral blood progenitor cell transplantation (PBPCT) is associated with faster hematopoietic recovery compared to bone marrow transplantation (BMT) and unmanipulated PBPCT may be associated with fewer postengraftment infections. We set out to evaluate and compare the incidence, cause, and outcome of postengraftment infections following HLA-identical sibling T cell-depleted PBPCT vs T cell-depleted BMT between days 30 and 365 posttransplant. Forty recipients of peripheral blood progenitor cells (PBPC) and 47 recipients of bone marrow (BM) were included. The two groups of patients were comparable with respect to their baseline characteristics. PBPC grafts contained significantly more CD34+ cells and PBPCT was associated with significantly faster neutrophil and lymphocyte recovery as compared to BMT. PBPC recipients experienced more chronic graft-vs-host disease (GVHD; 55% vs 34%; p=0.02). The number of definite and clinical infections per 100 patient days was comparable between recipients of PBPC and BM with similar contribution of causative microorganisms. At one year post SCT, 68% of PBPC recipients had experienced at least one CTC grade 3-4 infection vs 65% of BM recipients. Treatment-related mortality at one year from transplantation was 34% after PBPCT vs 30% after BMT, and no difference in infection-related mortality was observed. Postengraftment infectious morbidity and mortality were comparable between recipients of PBPC and BM despite a higher CD34+ cell content of PBPC grafts and faster lymphocyte recovery after PBPCT, which may in part be explained by the higher incidence of chronic GVHD.


Utilizing an o-Quinone Methide in Asymmetric Transfer Hydrogenation: Enantioselective Synthesis of Brosimine A, Brosimine B, and Brosimacutin L.
A concise and highly enantioselective synthesis of the flavonoids brosimine A, brosimine B, and brosimacutin L is reported for the first time. The key transformation is a single-step conversion of a flavanone into a flavan by means of an asymmetric transfer hydrogenation/deoxygenation cascade.


Solvent effects of a dimethyldicyanoquinonediimine buffer layer as N-type material on the performance of organic photovoltaic cells.
In the present work, we have fabricated organic photovoltaic cells consisting of ITO/PEDOT:PSS/P3HT:PCBM/DMDCNQI/Al using a dip-coating method with various solvent systems. We have investigated solvent effects (such as solubility, viscosity and vapor pressure) in deposition of a thin DMDCNQI buffer layer on the performance of organic photovoltaic cells. The solvent system which had low viscosity and good solubility properties, made a dense and uniform DMDCNQI ultra thin film, resulting in a high performance device. In particular, a prepared organic photovoltaic cell was fabricated using a cosolvent system (methanol:methylenechloride = 3:1) and showed a maximum power conversion efficiency of 4.53%.


Evolution of benign rheumatoid nodules into rheumatoid arthritis after 50 years.
A patient with benign rheumatoid nodules who developed rheumatoid arthritis after 50 years is described.


Physics-based RNA structure prediction.
Despite the success of RNA secondary structure prediction for simple, short RNAs, the problem of predicting RNAs with long-range tertiary folds remains. Furthermore, RNA 3D structure prediction is hampered by the lack of the knowledge about the tertiary contacts and their thermodynamic parameters. Low-resolution structural modeling enables us to estimate the conformational entropies for a number of tertiary folds through rigorous statistical mechanical calculations. The models lead to 3D tertiary folds at coarse-grained level. The coarse-grained structures serve as the initial structures for all-atom molecular dynamics refinement to build the final all-atom 3D structures. In this paper, we present an overview of RNA computational models for secondary and tertiary structures' predictions and then focus on a recently developed RNA statistical mechanical model-the Vfold model. The main emphasis is placed on the physics behind the models, including the treatment of the non-canonical interactions in secondary and tertiary structure modelings, and the correlations to RNA functions.


The ionization and distribution behavior of oleic acid in chylomicrons and chylomicron-like emulsion particles and the influence of serum albumin.
A reproducible, fairly narrow-sized population of rat lymph chylomicrons, approximately 100 nm, was isolated by centrifugation and combined with low levels of [1-13C]oleic acid for NMR studies. The carboxyl chemical shift was monitored as a function of aqueous pH to characterize the ionization behavior of the fatty acid in these particles. The titration curves were very similar to those for oleic acid in equivalent-sized emulsion particles composed of egg phosphatidylcholine and triolein. A simple partition-ionization model was fitted to the data to derive values for apparent ionization constant, expressed as pKapp, of 7.4-7.5 and the "true" surface to core partition coefficient of approximately 7 for oleic acid in chylomicrons. The fatty acid in chylomicrons thus appeared to be largely associated with the surface regions of these particles. Addition of bovine serum albumin to the samples showed that near physiologic pH much of the fatty acid was bound to the albumin at fatty acid to albumin-binding stoichiometries as high as 5.1 and with mass ratios of greater than 2 in favor of the lipid or lipoprotein particles. Lowering the pH of the medium shifted the distribution of fatty acid away from albumin so that at pH 5 with the emulsion, virtually all the fatty acid was associated with the lipid. The behavior observed under physiologic conditions is consistent with the rapid clearance and redistribution of fatty acid generated in these particles by lipolytic processes. However, under conditions of severe acidosis, hyperlipidemia, and hypoalbuminemia a significant portion of fatty acids might be retained in triglyceride-rich lipoproteins and their remnants and affect subsequent metabolism.


Whole-agent selectivity within the macaque face-processing system.
The primate brain contains a set of face-selective areas, which are thought to extract the rich social information that faces provide, such as emotional state and personal identity. The nature of this information raises a fundamental question about these face-selective areas: Do they respond to a face purely because of its visual attributes, or because the face embodies a larger social agent? Here, we used functional magnetic resonance imaging to determine whether the macaque face patch system exhibits a whole-agent response above and beyond its responses to individually presented faces and bodies. We found a systematic development of whole-agent preference through the face patches, from subadditive integration of face and body responses in posterior face patches to superadditive integration in anterior face patches. Superadditivity was not observed for faces atop nonbody objects, implying categorical specificity of face-body interaction. Furthermore, superadditivity was robust to visual degradation of facial detail, suggesting whole-agent selectivity does not require prior face recognition. In contrast, even the body patches immediately adjacent to anterior face areas did not exhibit superadditivity. This asymmetry between face- and body-processing systems may explain why observers attribute bodies' social signals to faces, and not vice versa. The development of whole-agent selectivity from posterior to anterior face patches, in concert with the recently described development of natural motion selectivity from ventral to dorsal face patches, identifies a single face patch, AF (anterior fundus), as a likely link between the analysis of facial shape and semantic inferences about other agents.


MR spectroscopy in a cervical abscess.
MR spectroscopy (MRS) has been used to analyse noninvasively tissues at a molecular level. Hydrogen and phosphorus MRS have been used for characterisation of intracranial solid and cystic masses, gynaecological tumours and lymph nodes. We report a cystic, tick-walled mass in the soft tissues of the neck. Single-voxel proton MRS revealed a prominent acetate peak at 1.92 ppm and a diagnosis of abscess was suggested. At operation a pyogenic neck abscess was confirmed, with culture of the pus.


Aortic wavelength as a determinant of the relation between heart rate and body size in mammals.
Measurements of aortic input impedance in the rat, dog, and man suggest a new hypothesis to explain the inverse correlation between rate and body size: that pulse wavelength and arterial length are matched in a way that minimizes cardiac work. The optimal rate is fast enough to avoid the high impedances produced by reflections at relatively low frequencies, yet slow enough to permit orderly excitation and recovery of the myocardium.


Myopic cracks, angioid streaks, and traumatic tears in Bruch's membrane.
We studied the pattern of break formation in 60 eyes with myopic lacquer cracks, angioid streaks, or traumatic tears in Bruch's membrane, using a graphics composition technique and computer analysis of digitized images. Lacquer cracks were found in a reticular distribution within a posterior staphyloma; angioid streaks occurred in a spider-web configuration centered on the optic nerve; traumatic tears were characteristically curved, perineural, and eccentric temporally. The specific break patterns imply the operation of biomechanical forces.


Increased capacity of lymphocytes to lyse tumor cells in vitro and production of lymphotoxins after cisplatin treatment.
Spleen lymphocytes from C3H/He mice when treated with cisplatin show increased cytostasis and cytotoxicity against Dalton's lymphoma cells in vitro. Cisplatin treatment of splenocytes does not render them cytotoxic/or cytostatic against normal splenocytes. Splenocytes on treatment with cisplatin also produce tumor cell-specific cytotoxic/cytostatic factors (lymphotoxins) which have cytolytic and cytostatic effect on Dalton's lymphoma cells. The increased cytotoxicity of splenocytes on treatment with cisplatin is reversed by the calcium channel blocker nifedipine and the calmodulin antagonist chlorpromazine, suggesting a role of calcium in cisplatin-activated lymphocyte-mediated cytotoxicity.


Assessment of a downsized potassium adsorption filter designed to transfuse neonates.
During storage, the potassium level of red blood cell (RBC) components increases, especially after irradiation. Neonates are prone to hyperkalemia, for example, non-oliguric hyperkalemia, so using potassium adsorption filters during transfusion may be helpful. To overcome dilution of RBC components caused by saline priming of existing potassium adsorption filters, a downsized potassium adsorption filter for neonates (PAF-n, Kawasumi Laboratories Inc., Tokyo, Japan) was developed. To assess the performance of PAF-n, its adsorption efficiency and RBC recovery rate were evaluated by testing pre-filtration and serial post-filtration (0-30 mL, 30-60 mL, 60-90 mL, and 90-120 mL) samples from 8 RBC components. The average potassium adsorption rate of the PAF-n was 90.5% ± 0.78%, and never less than 89.0% in any of 8 RBC components. RBC recovery rates were 99.3% ± 1.12%. The PAF-n showed an effective potassium ability with negligible RBC dilution.


Failure of thapsigargin to alter ion transport in human sweat gland epithelia while intracellular Ca2+ concentration is raised.
Cai in cultured human sweat gland epithelial monolayers was measured using Fura-2 fluorescence. Thapsigargin (Tg) caused a sustained increase in Cai, the rate of rise being slower but the magnitude greater than with the agonists lysylbradykinin and ATP. Tg caused an irreversible change such that even after it was removed Cai was dependent on the ambient calcium concentration, consistent with the hypothesis that Ca2+ entry is controlled by the state of the intracellular stores. Calcium entry after Tg was not modified by nimodipine, omega-conotoxin, or BAY K8644 but could be blocked by low concentrations (0.5 mM) of La3+. High concentrations of La3+ (2 mM) caused an increase in the response to Tg, suggesting that membrane ATPase exerts a major Cai lowering effect. Intracellular Ca2+ ion chelation with 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid significantly blunted the response to Tg. Finally, Mn2+ entry rate into epithelial cells was doubled by Tg. In spite of the evidence that Tg raises Cai to values greater and for longer than calcium requiring agonists only the latter affected transepithelial transport processes. It is shown that Tg neither affects transepithelial sodium transport nor chloride conductance, both of which increase in response to lysylbradykinin or ATP. It is concluded that spatio-temporal patterns of Cai increase after Tg and other agonists are different.


Predictors for recurrence after urethroplasty in pediatric and adolescent stricture urethra.
This study aims at evaluating factors predicting recurrence of urethral stricture following urethroplasty in pediatric patients at a tertiary care center. Fifty-two patients of up to 18 years of age, who underwent urethroplasty, were reviewed. Duration of symptoms, etiology, previous intervention, and site of stricture, surgical modality, stricture length, and spongiofibrosis at stricture site, recurrence, and ancillary procedures required were recorded. Forty-two (82.76%) patients (Group I) had recurrence-free course on follow-up. Of the 10 patients with recurrence (Group II), 9 had PTS and 1 had IS (p = 0.04). Most of the factors evaluated did not differ statistically between the groups; however, length of stricture (1.8 vs. 4.3 cm, p < 0.001) and degree of spongiofibrosis (61% vs. 90%, p = 0.003) were significantly different. Seven patients with recurrence were managed with single procedures, but three required multiple procedures because of multiple recurrences. History of incision and drainage for paraurethral abscess was significantly higher (28.6% vs. 100%, p = 0.002) in patients who had multiple recurrences. Etiology, fibrosis at local site, and stricture length have significant impact on recurrence of pediatric urethral stricture disease. Associated paraurethral abscess may further compromise the outcome of urethroplasty.


Inter-muscle differences in modulation of motor evoked potentials and posterior root-muscle reflexes evoked from lower-limb muscles during agonist and antagonist muscle contractions.
Voluntary contraction facilitates corticospinal and spinal reflex circuit excitabilities of the contracted muscle and inhibits spinal reflex circuit excitability of the antagonist. It has been suggested that modulation of spinal reflex circuit excitability in agonist and antagonist muscles during voluntary contraction differs among lower-limb muscles. However, whether the effects of voluntary contraction on the excitabilities of corticospinal and spinal reflex circuits depend on the tested muscles remains unknown. The purpose of this study was to examine inter-muscle differences in modulation of the corticospinal and spinal reflex circuit excitabilities of multiple lower-limb muscles during voluntary contraction. Eleven young males performed isometric plantar-flexion, dorsi-flexion, knee extension, and flexion at low torque levels. Motor evoked potentials (MEPs) and posterior root-muscle reflexes from seven lower-leg and thigh muscles were evoked by transcranial magnetic stimulation and transcutaneous spinal cord stimulation, respectively, at rest and during weak voluntary contractions. MEP and posterior root-muscle reflex amplitudes of agonists were significantly increased as agonist torque level increased, except for the reflex of the tibialis anterior. MEP amplitudes of antagonists were significantly increased in relation to the agonist torque level, but those of the rectus femoris were slightly depressed during knee flexion. Regarding the posterior root-muscle reflex of the antagonists, the amplitudes of triceps surae and the hamstrings were significantly decreased, but those of the quadriceps femoris were significantly increased as the agonist torque level increased. These results demonstrate that modulation of corticospinal and spinal reflex circuit excitabilities during agonist and antagonist muscle contractions differed among lower-limb muscles.


Characteristics of a MR-compatible ankle exercise ergometer for a 3.0 T head-only MR scanner.
An exercise ergometer, for isometric or dynamic contraction of both dorsiflexion and/or plantarflexion exercise, was designed and constructed for a 3.0 T head-only MR scanner. The principal features of this MR-compatible ergometer include electronic devices for quantification of force (during isometric exercise) and angular displacement (during dynamic exercise), without any significant losses to external motions or frictions. The ergometer was also made to be adjustable for subject leg length and was designed for suspension within the bore of the magnet to eliminate transmission of force and vibration to the MR scanner. A description of the design and construction, as well as the important technical features, is presented herein.


Impact of high-fat diet and voluntary running on body weight and endothelial function in LDL receptor knockout mice.
Obesity and physical inactivity are important cardiovascular risk factors. Regular physical exercise has been shown to mediate beneficial effects in the prevention of cardiovascular diseases. However, the impact of physical exercise on endothelial function in proatherosclerotic low-density lipoprotein receptor deficient (LDLR(-/-)) mice has not been studied so far. Six-week-old male LDLR(-/-) mice were fed a standard diet or a high-fat diet (39 kcal% fat diet) for 20 weeks. The impact of high-fat diet and voluntary running on body weight and amount of white adipose tissue was monitored. Basal tone and endothelial function was investigated in aortic rings using a Mulvany myograph. LDLR(-/-) mice on high-fat diet had increased cumulative food energy intake, but also higher physical activity compared to mice on control diet. Body weight and amount of visceral and retroperitoneal white adipose tissue of LDLR(-/-) mice were significantly increased by high-fat diet and partially reduced by voluntary running. Endothelial function in aortae of LDLR(-/-) mice was impaired after 20 weeks on standard and high-fat diet and could not be improved by voluntary running. Basal tone showed a trend to be increased by high-fat diet. Voluntary running reduced body weight and amount of white adipose tissue in LDLR(-/-) mice. Endothelial dysfunction in LDLR(-/-) mice could not be improved by voluntary running. In a clinical context, physical exercise alone might not have an influence on functional parameters and LDL-C levels in patients with familial hypercholesterolemia. However, physical activity in these patients may be in general beneficial and should be performed.


Enhanced external counterpulsation (EECP) decreases advanced glycation end products and proinflammatory cytokines in patients with non-insulin-dependent type II diabetes mellitus for up to 6 months following treatment.
Enhanced external counterpulsation (EECP) is a noninvasive, non-pharmacologic intervention proven to increase nitric oxide bioavailability in patients with coronary artery disease. The purpose of the present study was to evaluate the potential clinical benefits of EECP on advanced glycation end products (AGEs) and proinflammatory cytokine concentrations in patients with a clinical diagnosis of type II diabetes mellitus (T2DM). Thirty subjects (60.7 ± 1.9 years) with T2DM were randomly assigned (2:1 ratio) to receive either 35 1-h sessions of EECP (n = 20) or time-matched standard care (n = 10). AGEs, receptors for AGEs (RAGEs), soluble vascular cell adhesion molecules-1 (sVCAM-1), and 8-iso-prostaglandin 2α (8-iso-PGF2α) were evaluated before and at 48 h, 2 weeks, 3, and 6 months following EECP treatment or time-matched control. EECP significantly decreased AGEs and RAGEs at all follow-up measurement time points. AGEs and RAGEs were decreased at 48 h (-75 and -16 %), 2 weeks (-87 and -28 %), 3 months (-89 and -29 %), and 6 months (-92 and -20 %) following EECP treatment, respectively. sVCAM-1 and 8-iso-PGF2α were significantly decreased at 48 h (-30 and -49 %) and 2 weeks (-22 and -27 %) following EECP, respectively. sVCAM-1 (-27 %) remained significantly reduced at 3 months following EECP. Nitrite/nitrate (NOx) was significantly increased at 48 h (+48.4 %) and 2 weeks (+51.9 %) following EECP treatment. Our findings provide novel evidence that EECP decreases AGE/RAGE concentrations, inflammation, and oxidative stress in patients with T2DM that persist for up to 6 months following treatment.


Objective Structured Clinical Examination (OSCE) in Psychiatry Education: A Review of Its Role in Competency-Based Assessment.
Over the last two decades, Objective Structured Clinical Examination (OSCE) has become an increasingly important part of psychiatry education and assessment in the Australian context. A reappraisal of the evidence base regarding the use of OSCE in psychiatry is therefore timely. This paper reviews the literature regarding the use of OSCE as an assessment tool in both undergraduate and postgraduate psychiatry training settings. Suitable articles were identified using the search terms 'psychiatry AND OSCE' in the ERIC (educational) and PubMed (healthcare) databases and grouped according to their predominant focus: (1) the validity of OSCEs in psychiatry; (2) candidate preparation and other factors impacting on performance; and (3) special topics. The literature suggests that the OSCE has been widely adopted in psychiatry education, as a valid and reliable method of assessing psychiatric competencies that is acceptable to both learners and teachers alike. The limited evidence base regarding its validity for postgraduate psychiatry examinations suggests that more research is needed in this domain. Despite any shortcomings, OSCEs are currently ubiquitous in all areas of undergraduate and postgraduate medicine and proposing a better alternative for competency-based assessment is difficult. A critical question is whether OSCE is sufficient on its own to assess high-level consultancy skills, and aspects of professionalism and ethical practice, that are essential for effective specialist practice, or whether it needs to be supplemented by additional testing modalities.


The continuing emergency care clinic: improving patient compliance with follow-up care.
Traditionally, emergency patients have been noted for high rates of noncompliance with appointments in outpatient clinics for follow-up care. S study of cases referred for follow-up care at the outpatient clinic of The Medical College of Pennsylvania showed that less than 20% of the patients kept their appointments. To cope with this problem, a Continuing Emergency Care (CEC) clinic was established on the assumption that a change in structural environment could change noncompliance behavior patterns. The clinic is a small unit near the emergency department, separate from the larger hospital outpatient clinic area. Patient compliance data were collected on each case referred to the CEC clinic during a three-month period. Findings showed a threefold increase in appointment compliance over the previous study in which referrals were made to the hospital clinics.


Molecular mechanisms underlying the function diversity of transcriptional factor IclR family.
The IclR family transcriptional factor is widespread and involves in diverse bacterial physio-pathological events, such as primary and secondary metabolism, virulence, quorum sensing, sporulation. Unlike other transcriptional factors which function as either activators or repressors, IclR can assume both role simutaneously. Its N-terminal domain possesses a helix-turn-helix DNA binding motif which can dimerize or tetramerize to bind target promoters, while the C-terminal domain is for the effector binding. The function of IclR varies with the effectors bound. Escherichia coli transcription factor IclR is the archetype of this family, which regulates the aceBAK operon responsible for the glyoxylate shunt. The sophisticated regulatory mechanisms underlying iclR was largely based on E. coli iclR. Information concerning the pathogen IclR, especially those of Mycobacterium tuberculosis is poor, and is pivotal to our understanding of its biology and development of new effective TB control measures.


THBS1, a fatty acid-related metabolic gene, can promote the development of laryngeal cancer.
Laryngeal cancer is the second most prevalent head and neck tumor and it is one of the most common malignancies of the upper respiratory tract. Fatty acid metabolism affects cancer cell biology in several ways, and alterations in fatty acid metabolism are characteristic of both tumorigenesis and metastasis. Despite advances in laryngeal cancer diagnosis and treatment over the years, there has been no significant improvement in survival or mortality. Studying the role of fatty acid metabolism-related genes in laryngeal cancer will facilitate our search for valuable biomarkers to guide prognostic management and treatment selection. We constructed a prognostic risk score model for fatty acid metabolism-related genes by downloading and analyzing laryngeal cancers from the TCGA and GEO databases. We predicted survival outcomes of laryngeal cancer patients using a prognostic risk score model of fatty acid metabolism-related genes and analyzed the resistance of laryngeal cancer in different individuals to multiple drugs. In addition, the relationship between the prognostic risk score model and cellular infiltration characteristics of the tumor microenvironment were investigated. Through the prognostic risk scoring model, the genes with risk-prompting effect and related to prognosis were screened out for further research. Through the study of gene expression levels in the TCGA database, we screened out 120 differentially expressed fatty acid metabolism genes. LASSO-Cox and Cox regression analyses identified nine genes associated with prognosis to construct a prognostic risk score model for genes related to fatty acid metabolism. Both TCGA and GEO confirmed that samples in the high-risk score group had a worse prognosis than those in the low-risk score group. We found significant differences between the high-risk and low-risk groups for 22 drugs (P < 0.05). In addition, we found differences in immune cell infiltration between the different risk score groups. Finally, through the risk assessment model, combined with multiple databases, THBS1, a high-risk and prognosis-related gene, was screened. We also found that THBS1 could promote the migration, invasion and proliferation of laryngeal cancer cells by constructing THBS1 knockout cell lines. In our study, we identified key fatty acid-related genes differentially expressed in laryngeal carcinoma that can be used to adequately predict prognosis using a comprehensive bioinformatic experimental approach. It was also found that THBS1, a high-risk and prognosis-related gene, may regulate the occurrence and development of laryngeal cancer through fatty acid metabolism, which has further helped us to explore the role of fatty acid metabolism genes in laryngeal cancer.


Modeling rear-end collisions including the role of driver's visibility and light truck vehicles using a nested logit structure.
This paper presents an analysis of the effect of the geometric incompatibility of light truck vehicles (LTV)--light-duty trucks, vans, and sport utility vehicles--on drivers' visibility of other passenger cars involved in rear-end collisions. The geometric incompatibility arises from the fact that most LTVs ride higher and are wider than regular passenger cars. The objective of this paper is to explore the effect of the lead vehicle's size on the rear-end crash configuration. Four rear-end crash configurations are defined based on the type of the two involved vehicles (lead and following vehicles). Nested logit models were calibrated to estimate the probabilities of the four rear-end crash configurations as a function of driver's age, gender, vehicle type, vehicle maneuver, light conditions, driver's visibility and speed. Results showed that driver's visibility and inattention in the following (striker) vehicle have the largest effect on being involved in a rear-end collision of configuration CarTrk (a regular passenger car striking an LTV). Possibly, indicating a sight distance problem. A driver of a smaller car following an LTV, have a problem seeing the roadway beyond the LTV, and therefore would not be able to adjust his/her speed accordingly, increasing the probability of a rear-end collision. Also, the probability of a CarTrk rear-end crash increases in the case that the lead vehicle stops suddenly.


Hyaluronan coating improves liver engraftment of transplanted human biliary tree stem/progenitor cells.
Cell therapy of liver diseases with human biliary tree stem cells (hBTSCs) is biased by low engraftment efficiency. Coating the hBTSCs with hyaluronans (HAs), the primary constituents of all stem cell niches, could facilitate cell survival, proliferation, and, specifically, liver engraftment given that HAs are cleared selectively by the liver. We developed a fast and easy method to coat hBTSCs with HA and assessed the effects of HA-coating on cell properties in vitro and in vivo. The HA coating markedly improved the viability, colony formation, and population doubling of hBTSCs in primary cultures, and resulted in a higher expression of integrins that mediate cell attachment to matrix components. When HA-coated hBTSCs were transplanted via the spleen into the liver of immunocompromised mice, the engraftment efficiency increased to 11% with respect to 3% of uncoated cells. Notably, HA-coated hBTSC transplantation in mice resulted in a 10-fold increase of human albumin gene expression in the liver and in a 2-fold increase of human albumin serum levels with respect to uncoated cells. Studies in distant organs showed minimal ectopic cell distribution without differences between HA-coated and uncoated hBTSCs and, specifically, cell seeding in the kidney was excluded. A ready and economical procedure of HA cell coating greatly enhanced the liver engraftment of transplanted hBTSCs and improved their differentiation toward mature hepatocytes. HA coating could improve outcomes of stem cell therapies of liver diseases and could be immediately translated into the clinic given that GMP-grade HAs are already available for clinical use.


Gone in 60 days: our first experience with a bioconvertible IVC filter.
The Sentry bioconvertible IVC filter (Boston Scientific, MA, USA) contains a bioabsorbable filament which hydrolyses after 60 days, allowing the arms of the filter to spring open, retract into the vessel wall and endothelialise, leaving an unobstructed IVC lumen.It is a novel treatment option for patients at transient risk of pulmonary emboli with a contraindication to anticoagulation. The device provides similar protection to other currently available devices against pulmonary emboli with minimal complications. It represents an effective alternative to retrievable filters, the removal of which is variously not attempted, not possible or associated with high complication rates.We review the literature which underpins the development of the bioconvertible filter. We describe our first deployment of the filter in an 85-year-old female with gastric malignancy (who subsequently underwent a subtotal gastrectomy) with a history of anaemia and previous pulmonary emboli. The availability of a bioconvertible filter constitutes a further step forward in the management of patients with potential or active thromboembolic disease.


Dyssegmental dysplasia in siblings: prenatal ultrasonic diagnosis.
Two cases of dyssegmental dysplasia (type Silverman-Handmaker) in siblings are presented. The first-born died at the age of 3 months and the second fetus was followed during pregnancy with ultrasound examinations. In the 20th week of gestation marked shortening of the extremities was found; a female infant showing the same radiologic bony malformations as the firstborn was born by cesarean section. These cases support the autosomal recessive inheritance and demonstrate the possibility of prenatal diagnosis in this type of micromelic dwarfism.


Cell cycle arrest induced by pisosterol in HL60 cells with gene amplification.
The leukemia cell line HL60 is widely used in studies of the cell cycle, apoptosis, and adhesion mechanisms in cancer cells. We conducted a focused cytogenetic study in an HL60 cell line, by analyzing GTG-banded chromosomes before and after treatment with pisosterol (at 0.5, 1.0, and 1.8 microg/ml), a triterpene isolated from Pisolithus tinctorius, a fungus collected in the Northeast of Brazil. Before treatment, 99% of the cells showed the homogeneously staining region (HSR) 8q24 aberration. After treatment with 1.8 microg/ml pisosterol, 90% of the analyzed cells lacked this aberration. We further performed a pulse test, in which the cells treated with pisosterol (0.5, 1.0, and 1.8 microg/ml) were washed and re-incubated in the absence of pisosterol. Only 30% of the analyzed cells lacked the HSR 8q24 aberration, suggesting that pisosterol probably blocks the cells with HSRs at interphase. No effects were detected at lower concentrations. At the highest concentration examined (1.8 microg/ml), pisosterol also inhibited cell growth, but this effect was not observed in the pulse test, reinforcing our hypothesis that, at the concentrations tested, pisosterol probably does not induce cell death in the HL60 line. The results found for pisosterol were compared with those for doxorubicin. Cells that do not show a high degree of gene amplification (HSRs and double-minute chromosomes) have a less aggressive and invasive behavior and are easy targets for chemotherapy. Therefore, further studies are needed to examine the use of pisosterol in combination with conventional anti-cancer therapy.


Plasma cell granuloma of the stomach.
A case of plasma cell granuloma of the stomach is described, only one similar case having been previously recorded. Differentiation from a neoplastic plasmacytoma was achieved by demonstrating the polyclonal nature of the plasma cells using an immunoperoxidase technique.


Aqueductal stenting with an intra-catheter endoscope--a technical note.
Aqueductoplasty as well as aqueductal stenting is an accepted therapy option in short-segment aqueductal stenosis and isolated fourth ventricle. Over the years, different techniques with only slight modifications by using a conventional neuroendoscope with a working sheath to introduce different instruments have been presented. In summary, the use of Fogarty balloon catheters or flexible endoscopes to pass the narrowed aqueduct is recommended. This technical report describes a substantially new technique for this purpose. Six patients underwent aqueductal stenting with a new intracatheter endoscope. Aqueductal stenting was possible in 4 out of 6 cases. No complications occurred. Handling of this new technique was good and easy without a prolonged learning curve. All four stents did work appropriately, and the procedure was considered to be successful. Of the two failures, the technique was abandoned and endoscopic third ventriculostomy (ETV) was performed in one. In the other case, suboccipital shunting was done. This technical report describes a substantially new technique for aqueductal stenting. The combination of an intracatheter miniature endoscope and a prepared ventricular catheter enables careful and elegant aqueductal stenting. Large or flexible endoscopes, balloons, or special instruments to place a stent have become completely obsolete in selected cases.


Pharmacogenomic considerations in the opioid management of pain.
Physicians continue to struggle with the clinical management of pain, in part because of the large interindividual variability in the efficacy, occurrence of side effects and undesired severe adverse drug reactions from the prescribed analgesics. Pharmacogenomics, the study of how an individual's genetic inheritance affects the body's response to medications, has an important role and can explain some of this interindividual variability. Genetic identification of known variant alleles that affect the pharmacokinetics or pharmacodynamics of medications used for pain management can enable physicians to select the appropriate analgesic drug and dosing regimen for an individual patient, instead of empirical selection and dosing escalation. In this article, clinically relevant pharmacogenomic targets for the management of opioid pain, including efflux transporters, proteins that metabolize drugs, enzymes that regulate the neurotransmitters that modulate pain, and opioid receptors, will be reviewed.


Development of 1-(4-(Substituted)piperazin-1-yl)-2-((2-((4-methoxybenzyl)thio)pyrimidin-4-yl)oxy)ethanones That Target Poly (ADP-Ribose) Polymerase in Human Breast Cancer Cells.
A number of uracil amides cleave poly (ADP-ribose) polymerase and therefore novel thiouracil amide compounds were synthesized and screened for the loss of cell viability in a human-estrogen-receptor-positive breast cancer cell line. The synthesized compounds exhibited moderate to significant efficacy against human breast cancer cells, where the compound 5e IC50 value was found to be 18 μM. Thouracil amide compounds 5a and 5e inhibited the catalytical activity of PARP1, enhanced cleavage of PARP1, enhanced phosphorylation of H2AX, and increased CASPASE 3/7 activity. Finally, in silico analysis demonstrated that compound 5e interacted with PARP1. Hence, specific thiouracil amides may serve as new drug-seeds for the development of PARP inhibitors for use in oncology.


Topographic guidance labels in a sensory projection to the forebrain.
Visual connections to the mammalian forebrain are known to be patterned by neural activity, but it remains unknown whether the map topography of such higher sensory projections depends on axon guidance labels. Here, we show complementary expression and binding for the receptor EphA5 in mouse retina and its ligands ephrin-A2 and ephrin-A5 in multiple retinal targets, including the major forebrain target, the dorsal lateral geniculate nucleus (dLGN). These ligands can act in vitro as topographically specific repellents for mammalian retinal axons and are necessary for normal dLGN mapping in vivo. The results suggest a general and economic modular mechanism for brain mapping whereby a projecting field is mapped onto multiple targets by repeated use of the same labels. They also indicate the nature of a coordinate system for the mapping of sensory connections to the forebrain.


Caudato-nigral transmission in the substantia nigra pars reticulata neurons changes with recovery from circling movements induced by microinfusion of ibotenic acid. II. Electrophysiological study on synaptic transmission.
Caudato-nigral synaptic transmission was examined by stimulation of the caudate nucleus while recording from nigral neurons in cats recovering from circling movements induced by a unilateral circumscribed lesion in the substantia nigra pars reticulata after microinfusion of ibotenic acid. Extra- and intracellular recording from neurons in lesion-spared areas of the substantia nigra pars reticulata indicated that the caudato-nigral synaptic action on the side ipsilateral to the lesion exhibited a shorter duration of inhibition and a larger amplitude of excitation as a means of compensating for the circling movements.


A method to study in vivo stability of DNA nanostructures.
DNA nanostructures are rationally designed, synthetic, nanoscale assemblies obtained from one or more DNA sequences by their self-assembly. Due to the molecularly programmable as well as modular nature of DNA, such designer DNA architectures have great potential for in cellulo and in vivo applications. However, demonstrations of functionality in living systems necessitates a method to assess the in vivo stability of the relevant nanostructures. Here, we outline a method to quantitatively assay the stability and lifetime of various DNA nanostructures in vivo. This exploits the property of intact DNA nanostructures being uptaken by the coelomocytes of the multicellular model organism Caenorhabditis elegans. These studies reveal that the present fluorescence based assay in coelomocytes of C. elegans is an useful in vivo test bed for measuring DNA nanostructure stability.


Palmitoylation of the β4-subunit regulates surface expression of large conductance calcium-activated potassium channel splice variants.
Regulatory β-subunits of large conductance calcium- and voltage-activated potassium (BK) channels play an important role in generating functional diversity and control of cell surface expression of the pore forming α-subunits. However, in contrast to α-subunits, the role of reversible post-translational modification of intracellular residues on β-subunit function is largely unknown. Here we demonstrate that the human β4-subunit is S-acylated (palmitoylated) on a juxtamembrane cysteine residue (Cys-193) in the intracellular C terminus of the regulatory β-subunit. β4-Subunit palmitoylation is important for cell surface expression and endoplasmic reticulum (ER) exit of the β4-subunit alone. Importantly, palmitoylated β4-subunits promote the ER exit and surface expression of the pore-forming α-subunit, whereas β4-subunits that cannot be palmitoylated do not increase ER exit or surface expression of α-subunits. Strikingly, however, this palmitoylation- and β4-dependent enhancement of α-subunit surface expression was only observed in α-subunits that contain a putative trafficking motif (… REVEDEC) at the very C terminus of the α-subunit. Engineering this trafficking motif to other C-terminal α-subunit splice variants results in α-subunits with reduced surface expression that can be rescued by palmitoylated, but not depalmitoylated, β4-subunits. Our data reveal a novel mechanism by which palmitoylated β4-subunit controls surface expression of BK channels through masking of a trafficking motif in the C terminus of the α-subunit. As palmitoylation is dynamic, this mechanism would allow precise control of specific splice variants to the cell surface. Our data provide new insights into how complex interplay between the repertoire of post-transcriptional and post-translational mechanisms controls cell surface expression of BK channels.


Psammomatous Cavernous Malformation Presenting as Drug-Resistant Epilepsy: Case Illustration and Review of Literature.
Psammoma bodies (PBs) are whorled, laminated hyaline spherules containing calcium deposits. Intracranially, the presence of PBs is associated with variants of meningioma and pituitary lesions, as well as aging choroid plexus. Limited information exists on their presence in vascular malformation. In this report, we describe a case of an adolescent male with drug-resistant epilepsy that was surgically managed at our regional epilepsy center. The epileptogenic focus was determined to be emanating from an indolent right insular lesion. Histopathologic evaluation showed the abundance of intravascular and perivascular PBs. Immunohistochemical evaluation confirmed the vascular origin using vascular markers. The unusual presence of PBs in a vascular lesion was unanticipated. Based on our case, we present the clinicoradiologic characteristics, supplemented with intraoperative findings, for this unusual lesion. In addition, because of the unusual presence of PBs in vascular lesions, we provide the findings of a systematic literature review to show the association of PBs with intracranial vascular lesions.


Life years lost associated with mental illness: A cohort study of beneficiaries of a South African medical insurance scheme.
People with mental illness have a reduced life expectancy, but the extent of the mortality gap and the contribution of natural and unnatural causes to excess mortality among people with mental illness in South Africa are unknown. We analysed reimbursement claims from South African medical insurance scheme beneficiaries aged 15-85 years. We estimated excess life years lost (LYL) associated with organic, substance use, psychotic, mood, anxiety, eating, personality, developmental or any mental disorders. We followed 1,070,183 beneficiaries for a median of three years, of whom 282,926 (26.4 %) received mental health diagnoses. Men with a mental health diagnosis lost 3.83 life years (95 % CI 3.58-4.10) compared to men without. Women with a mental health diagnosis lost 2.19 life years (1.97-2.41) compared to women without. Excess mortality varied by sex and diagnosis, from 11.50 LYL (95 % CI 9.79-13.07) among men with alcohol use disorder to 0.87 LYL (0.40-1.43) among women with generalised anxiety disorder. Most LYL were attributable to natural causes (men: 3.42, women: 1.94). A considerable number of LYL were attributable to unnatural causes among men with bipolar (1.52) or substance use (2.45) disorder. Mental diagnoses are based on reimbursement claims. Premature mortality among South African individuals with mental disorders is high. Our findings support interventions for the prevention, early detection, and treatment of physical comorbidities in this population. Targeted programs for suicide prevention and substance use treatment, particularly among men, can help reduce excess mortality from unnatural causes.


Retinal vascular oximetry during ranibizumab treatment of central retinal vein occlusion.
To investigate the effect of intravitreal injections of the vascular endothelial growth factor inhibitor ranibizumab on retinal oxygenation in patients with central retinal vein occlusion (CRVO). Retinal oxygen saturation in patients with CRVO was analysed using the Oxymap Retinal Oximeter P3, before and during 6 months of treatment with intravitreal injections of ranibizumab. At presentation, retinal venous oxygen saturation was lower in eyes with CRVO than in the healthy fellow eyes (32±13% vs 59±10%, respectively, p=0.001) whereas retinal arterial saturation was higher in eyes with CRVO than in the fellow eyes (95%±8% and 91%±3%, p=0.04). Mean visual acuity increased from 51±24 letters ETDRS at baseline to 66±24 and 69±20 letters ETRDS, respectively, at 3 months and 6 months treatment (mean±SD, p<0.0001, repeated measures analysis of variance) and central retinal thickness was reduced from 697±139 µm to 368±113 µm and 340±96 µm, respectively, from baseline to 3 months and 6 months treatment (p<0.0001). Venous saturation increased during treatment (from 35.5%±13.8% at baseline to 43.1%±10.8% and 43.5%±13.7% after 3 months and 6 months treatment, respectively, p=0.012), while no significant change was found in arterial saturation (p=0.24). Retinal venous oxygen saturation was markedly reduced in untreated CRVO and was roughly halfway normalised during intravitreal ranibizumab treatment. Retinal artery oxygen saturation was not reduced in CRVO. NCT01360385.


Change in functional status of patients whilst awaiting prinmary total knee arthroplasty.
To investigate the effect of waiting lists on the rate of change in the functional status of patients awaiting total knee joint replacement. The Oxford knee score, a measure of functional status, was taken both at listing for operation and just prior to surgery for 58 patients listed for total knee replacement. The distribution of scores initially and pre-operatively were found to be normally distributed using the Kolmogorov-Smirnov test, therefore the paired t-test was used to compare the statistical significance. Waiting times were not normally distributed and the Spearmann rank correlation test was used to correlate waiting time and initial score and change in score.


Influence of inoculation time of an autochthonous selected malolactic bacterium on volatile and sensory profile of Tempranillo and Merlot wines.
A study was carried out to determine the effect of the inoculation time of the lactic acid bacteria (LAB) on the kinetic of vinification and on chemical and sensory characteristics of Tempranillo and Merlot wines. Traditional vinifications, with LAB inoculated after completion of AF, were compared with vinifications where yeast and bacteria were co-inoculated. Two commercial yeast strains and an autochthonous Oenococcus oeni strain (C22L9) previously identified and selected at our laboratory were used. Monitoring of alcoholic and malolactic fermentations was carried out by yeast and lactic acid bacteria counts and by measuring contents of glucose+fructose, malic acid and lactic acid. The implantation rate of O. oeni C22L9 was calculated by typing isolates obtained from count plates using the RAPD-PCR (Randomly Amplified Polymorphic DNA-Polymerase Chain Reaction) technique. Wines were chemically characterised and analysed for biogenic amine and volatile compound contents. A sensory analysis, consisting in a descriptive and a triangular test was also carried out. Results from this study showed that for both grape varieties, the concurrent yeast/bacteria inoculation of musts produced a significant reduction in duration of the process, without a pronounced degradation of malic acid during AF, nor an excessive increase in volatile acidity. Biogenic amine content was also lower in wines produced by co-inoculation. Important differences in volatile compound contents were observed, although there was little impact on the sensorial profile of wines. These results suggest that co-inoculation using O. oeni C22L9 is a worthwhile alternative compared to traditional post AF inoculation for Tempranillo and Merlot winemaking.


OCGR array: an oral cancer genomic regional array for comparative genomic hybridization analysis.
Genetic alterations have been recognized as important events in the carcinogenesis of oral squamous cell carcinoma (OSCC) and have been used as predictors of progression risk. In this study, we have designed an oral cancer-specific human bacterial artificial chromosome (BAC) array, called the oral cancer genomic regional array (OCGR), to detect and fine map copy number alterations in OSCC. This array contains a total of approximately 45 Mbp coverage of nine chromosomal regions reported to be involved in the progression of oral cancer. We demonstrate the detection of copy number alterations in 14 microdissected clinical specimens in each of the nine regions. These include both copy number increases and decreases. Although the number of regions selected for this first generation array is small, we observed multiple segmental changes. In some cases, we observed single BAC clone alterations at 7p11 and 11q13 which contain EGFR and cyclin D1 respectively highlighting the need for high resolution detection techniques. Array comparative genomic hybridization (CGH) complements traditional methods for detecting genetic alterations in OSCC (such as microsatellite and CGH analysis) by improving the detection of segmental copy number alterations to single BAC clone resolution. This work represents the first attempt at the construction of an oral cancer-specific CGH array.


Subtype IV of the BK polyomavirus is prevalent in East Asia.
BK polyomavirus (BKV) is ubiquitous in human populations, infecting children asymptomatically and then persisting in the kidney. Using either serological or genotyping methods, BKV isolates have been classified into four subtypes (I-IV), with subtype I mainly detected in all countries studied so far. To elucidate the subtype of BKV prevalent in East Asia, we examined BKV-positive urine samples collected from immunocompetent elderly patients in Mongolia, Northeast China, Northwest China, Southeast China, Southwest China, Vietnam and Japan. The 287-bp typing region of the viral genome in each of these samples was PCR-amplified and sequenced, and a phylogenetic tree was constructed. According to the tree, BKV isolates in East Asia were unambiguously classified into subtype I or IV (subtypes II and III were not detected). In Japan, subtype I was mainly detected and subtype IV was rare, whereas in the other regions subtype IV was detected frequently, at rates ranging from 24 to 100%. Thus, East Asia (excluding Japan) is a region in which subtype-IV BKV is prevalent, a finding that requires the view of the geographic distribution of BKV subtypes to be revised. Furthermore, we present evidence that the immunological states of urine donors do not affect the pattern of BKV subtypes.


Knowledge management in clinical practice: a systematic review of information seeking behavior in physicians.
To determine information seeking behavior of physicians. Systematic review of 19 studies that described information seeking behavior in a number of different settings using differing methodologies. Analysis was limited to quantitative studies describing sources of information sought by physicians. Investigators have used questionnaires, interviews and observation to identify the information seeking behavior of clinicians. The results were mainly obtained from trials in the United States and showed a wide variation in primary information sources used by physicians. The most frequent source for information used are text sources, second is asking colleagues and only one study found electronic databases to be the primary resource. Physician's desk reference is the commonest cited printed resource. Convenience of access, habit, reliability, high quality, speed of use, and applicability makes information seeking likely to be successful and to occur. The lack of time to search, the huge amount of material, forgetfulness, the belief that there is likely to be no answer, and the lack of urgency all hinder the process of answering questions. The wide variation in information seeking behavior implies a need for further categorization of information need and information sources. Careful planning of information delivery to physicians is required to enable them to keep up to date and to improve knowledge transfer.


Impact of prior cancer history on the survival of patients with larynx cancer.
Patients with a prior history of cancer are commonly excluded from clinical trial. Increasing number of studies implied that a prior cancer did not adversely affect the clinical outcome among various types of cancer patients. However, the impact of prior cancer on survival of larynx cancer patients remains largely unknown. The aim of this study was to evaluate the prevalence of prior cancer and assess its impact on survival of patients diagnosed with larynx cancer. Patients with larynx cancer as the first or second primary malignancy diagnosed from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was conducted to balance baseline characteristics. Kaplan-Meier method, multivariate Cox proportional hazard model, and multivariate competing risk model were performed for survival analysis. A total of 24,812 eligible patients with larynx cancer were included in the study, wherein a total of 2436 patients (9.8%) had a prior history of cancer. Prostate (36%), lung and bronchus (10%), urinary bladder (7%), and breast (6%) were the most common types of prior cancer. A prior cancer history served as a risk factor for overall survival (AHR =1.30; 95% CI [1.21-1.41]; P < 0.001) but a protective factor for cancer-specific mortality (AHR = 0.83; 95% CI [0.72-0.94]; P = 0.004) in comparison with those without prior cancer. The subgroup analysis showed that a prior history of cancer adversely affected overall survival of patients with larynx cancer in most subgroups stratified by timing and types of prior cancer, as well as by different clinicopathologic features. Our study indicated an adverse survival impact of a prior history of cancer on patients with larynx cancer. Except for a few particular prior cancer, clinical trials should be considered prudently for laryngeal cancer patients with prior cancers.


A general assay for monitoring the activities of protein tyrosine phosphatases in living eukaryotic cells.
Protein tyrosine phosphatases (PTPs) are key signal-transduction regulators and have emerged as potential drug targets for inhibitor design. Here we report a yeast-based assay that provides a general means of assessing the activity and/or inhibition of essentially any classical PTP in living cells. The assay uses the activity of an exogenously expressed PTP to counter the activity of a coexpressed and toxic tyrosine kinase, such that only active PTPs are capable of rescuing growth. PTP activity gives rise to both increased growth and decreased phosphotyrosine levels; cellular PTP activity can therefore be monitored by either yeast-growth curves or anti-phosphotyrosine Western blots. We show that four PTPs (TCPTP, Shp2, PEST, PTPα) are capable of rescuing the effects of v-Src toxicity. Since these PTPs are chosen from four distinct subfamilies, it is likely that biologically and medicinally important PTPs from other subfamilies can similarly function in the cellular PTP assay. Because many small-molecule PTP inhibitors fail to penetrate cell membranes effectively, this cell-based assay has the potential to serve as a useful screening tool for determining the cellular efficacy of candidate inhibitors in a more biologically relevant context than can be provided by an in vitro PTP assay.


Association of solidarity between adult children and older parents with cognitive decline.
The purpose of the present study was to investigate the association between older adults' contact with their adult children and their cognitive decline. Furthermore, contact with children was considered in terms of visual contact and non-visual contact. Data from the Korean Longitudinal Study of Aging from 2006 to 2014 was assessed using longitudinal data analysis, and 6634 participants were included at baseline with no missing information. The χ2 -test and generalized linear mixed model with a binary distribution were used to investigate the association between solidarity of adult children and parents, and cognitive decline. Non-visual contact with the first-born child was significantly associated with cognitive decline. With daily contact as the reference: for two to three times weekly, the OR was 1.224 (P = 0.033); for two to three times monthly, the OR was 1.357 (P = 0.003); for five to six times yearly, the OR was 1.3816 (P = 0.008); and for very rarely, the OR was 1.786 (P < 0.0002), showing a significant effect for all groups. In the final sex-, age- and marriage status-specific analysis, non-visual contact with the first-born child was significantly associated with cognitive decline for women, people aged ≤64 years and people who were married. The present study validated previous research on the importance of social contact, and further assessed different modes of contact to show that non-visual contact is more beneficial than visual contact in terms of cognitive decline. Geriatr Gerontol Int 2018; 18: 1501-1506.


Congenital tracheoesophageal fistula without esophageal atresia.
Congenital tracheoesophageal fistula (TEF) without esophageal atresia, commonly referred to as H-type fistula, comprises only 4.2% of all TEF's. Four infants with this entity were surgically treated at Santa Rosa Children's Hospital during the period of 1974 to 1977, and their diagnosis, surgical management, and hospital course are described in detail. H-type TEF is characterized by a clinical triad consisting of paroxysms of coughing precipitated by feeding, gaseous distention of the gastrointestinal tract, and pneumonitis. Demonstration of H-type TEF can be difficult and may be accomplished only by repeated examinations. The esophagogram using cinefluoroscopy and image intensification is the primary diagnostic technique utilized. If this is nondiagnostic, then tracheobronchoscopy should be performed in conjunction with ancillary techniques which improve endoscopic yield. Surgical correction can be accomplished through a cervical approach in 80% of cases. Preoperatival treatment of H-type TEF is dependent upon a high index of suspicion, an aggressive diagnostic approach, and prompt surgical correction. Our series of patients demonstrates that early diagnosis is feasible.


Discovery of N-arylalkyl-3-hydroxy-4-oxo-3,4-dihydroquinazolin-2-carboxamide derivatives as HCV NS5B polymerase inhibitors.
The metal ion chelating β-N-hydroxy-γ-ketocarboxamide pharmacophore was integrated into a quinazolinone scaffold, leading to N-arylalkyl-3-hydroxy-4-oxo-3,4-dihydroquinazolin-2-carboxamide derivatives as hepatitis C virus (HCV) NS5B polymerase inhibitors. Lead optimization led to the identification of N-phenylpropyl carboxamide 9 k (IC(50) =8.8 μM). Compound 9 k possesses selectivity toward HCV1b replicon Ava.5 cells (EC(50) =17.5 μM) over parent Huh-7 cells (CC(50) =187.5 μM). Compound 9 k effects a mixed mode of NS5B inhibition, with NTP-competitive displacement properties. The interaction between 9 k and NS5B is stabilized by the presence of magnesium ions. Docking studies showed that the binding orientation of 9 k occupies the central portions of both magnesium-mediated and NTP-ribose-response binding sites within the active site region of NS5B. As a result, 3-hydroxy-4-oxo-3,4-dihydroquinazolin-2-carboxamide derivatives are disclosed herein as novel, mainly active site inhibitors of HCV NS5B polymerase.


A pharmacoeconomical model for choice of a treatment for pregnant women with gestational diabetes.
This study discusses two main questions: the direct medical costs and the clinical effectiveness of the hospital treatment with insulin of pregnant women with gestational diabetes (GD). A prospective study that includes 50 women with GD is performed. The pregnant women are divided into 2 groups: Group I (n=30) - pregnant women treated only with a diet; and Group II (n=20) - pregnant women treated with diet and insulin. We found that the metabolite compensation degree is improved after the applied treatment with insulin. The coefficient cost/effectiveness is 6954 lv./100 women. The analysis decision tree confirms in a very convenient way the fact that insulin treatment is a clinically more effective and financially more profitable strategy.


Organics and nitrogen removal and sludge stability in aerobic granular sludge membrane bioreactor.
Novel aerobic granular sludge membrane bioreactor (GMBR) was established by combining aerobic granular sludge technology with membrane bioreactor (MBR). GMBR showed good organics removal and simultaneous nitrification and denitrification (SND) performances for synthesized wastewater. When influent total organic carbon (TOC) was 56.8-132.6 mg/L, the TOC removal of GMBR was 84.7-91.9%. When influent ammonia nitrogen was 28.1-38.4 mg/L, the ammonia nitrogen removal was 85.4-99.7%, and the total nitrogen removal was 41.7-78.4%. Moreover, batch experiments of sludge with different particle size demonstrated that: (1) flocculent sludge under aerobic condition almost have no denitrification capacity, (2) SND capacity was caused by the granular sludge, and (3) the denitrification rate and total nitrogen removal efficiency were enhanced with the increased particle size. In addition, study on the sludge morphology stability in GMBR showed that, although some granular sludge larger than 0.9 mm disaggregated at the beginning of operation, the granular sludge was able to maintain the stability of its granular morphology, and at the end of operation, the amount of granular sludge (larger than 0.18 mm) stabilized in GMBR was more than 56-62% of the total sludge concentration. The partial disaggregation of large granules is closely associated with the change of operating mode from sequencing batch reactor (SBR) system to MBR system.


Side-Chain Engineering of Benzodithiophene-Bridged Dimeric Porphyrin Donors for All-Small-Molecule Organic Solar Cells.
Two new A-D-A small-molecule donors (C8T-BDTDP and C8ST-BDTDP) are prepared from benzodithiophene (BDT)-linked dimeric porphyrin (DP), which differ in side chains of BDT linkers with 4,8-bis[5-(2-ethylhexyl)thiophen-2-yl]benzo[1,2-b:4,5-b']dithiophene (C8T-BDT) for the former and 4,8-bis{5-[(2-ethylhexyl)thio]-2-thienyl}benzo[1,2-b:4,5-b']dithiophene (C8ST-BDT) for the latter. Both dimeric porphyrin donors show strongly UV-visible to near-infrared absorption. Compared to C8T-BDTDP, C8ST-BDTDP with an alkylthiothienyl-substituted BDT linker exhibits more intense absorption bands in the film and a lower highest occupied molecular orbital energy level. The blend film of the electron acceptor 6TIC with the respective dimeric porphyrin donor displays a broad photon response from 400 to 900 nm, unfortunately, with an absorption valley at ca. 600 nm. The device based on C8ST-BDTDP/6TIC demonstrates a promising power conversion efficiency (PCE) of 10.39% with a high short-circuit current density (JSC) of 19.53 mA cm-2, whereas the device based on C8T-BDTDP/6TIC shows a slightly lower PCE of 8.73% with a JSC of 17.75 mA cm-2. The better performance for C8ST-BDTDP/6TIC is mainly attributed to efficient charge dissociation and transportation because of the smooth surface morphology and highly ordered crystalline packing.


Ideological and logistical barriers to the development of nursing research: real or imagined?
Australian nurses sit amidst a treasure-trove of developing knowledge, and yet are dragging their feet when it comes to nursing research. Barriers or 'perceived' barriers to the development of nursing research in this country are explored. These include ideological concerns, economic constraints, and infrastructural factors. A set of recommendations, which may assist nurses in attaining a research profile in keeping with the status of a profession is offered.


Elucidating the richness of bacterial groups in the gut of Nicobarese tribal community - Perspective on their lifestyle transition.
Lifestyle and dietary habits are crucial features that can alter the gut microbiome of humans. Humans, along with their gut microbes, have coevolved in order to sustain themselves in different environments. They were able to adapt themselves to the dietary sources available in their environment. The relation between humans and their gut microbiota and the link with coevolution forms an interesting aspect of research. To understand this association, the participation of ancient communities with less exposure to urbanization is a prerequisite. The current study quantifies the richness of bacterial groups in the gut of Nicobarese. This group of population is an ethnic community of Nicobar group of islands, who have migrated from the remote to rural and urban areas. Alterations in the dominant bacterial groups in relation to their lifestyle transition were emphasized, by comparing the participants from remote, rural and urban settings. The remote cohort remains diverse and stable than the other two cohorts and had higher numbers of Bacteroidetes. Prevotella forms the dominant genus in the Bacteroidetes phylum, indicating the carbohydrate-rich diet of remote Nicobarese. Whereas, the urban cohort is dominated by Bifidobacterium group rather than the Bacteroidetes. Implications of dietary patterns, the transition to different lifestyles and their impact on the microbiota among these cohorts are discussed.


More precisely biased: increasing the number of markers is not a silver bullet in genetic bottleneck testing.
In response to our review of the use of genetic bottleneck tests in the conservation literature (Peery et al. 2012,Molecular Ecology, 21, 3403–3418), Hoban et al. (2013, Molecular Ecology, in press) conducted population genetic simulations to show that the statistical power of genetic bottleneck tests can be increased substantially by sampling large numbers of microsatellite loci, as they suggest is now possible in the age of genomics. While we agree with Hoban and co-workers in principle, sampling large numbers of microsatellite loci can dramatically increase the probability of committing type 1 errors(i.e. detecting a bottleneck in a stable population) when the mutation model is incorrectly assumed. Using conservative values for mutation model parameters can reduce the probability of committing type 1 errors, but doing so can result in significant losses in statistical power. Moreover, we believe that practical limitations associated with developing large numbers of high-quality microsatellite loci continue to constrain sample sizes, a belief supported by a literature review of recent studies using next generation sequencing methods to develop microsatellite libraries. conclusion, we maintain that researchers employing genetic bottleneck tests should proceed with caution and carefully assess both statistical power and type 1 error rates associated with their study design.


Long-term clinical follow-up and molecular genetic findings in eight patients with triple A syndrome.
The triple A syndrome (Allgrove syndrome, OMIM #231550) is caused by autosomal recessively inherited mutations in the AAAS gene on chromosome 12q13 encoding the nuclear pore protein ALADIN. This multisystemic disease is characterised by achalasia, alacrima, adrenal insufficiency and neurological impairment. We analyse long-term clinical follow-up and results of sequencing of the AAAS gene in eight patients with triple A syndrome aged from 2 to 35 years. At the time of diagnosis, all patients presented with alacrima, neurological dysfunction, dermatological abnormalities, seven of them with adrenal insufficiency and five of them with achalasia. Sequencing of the AAAS gene identified the p.S263P mutation in five of eight patients, supporting the hypothesis that this mutation is a founder mutation in Slavic population. One of the patients is homozygous for the p.S263P mutation, two are compound heterozygous for the p.S263P and the p.G14fs mutation, two are compound heterozygous for the p.S263Pro mutation and p.S296Y mutation, two are compound heterozygous for the p.G14fs and the p.Q387X mutations and one is homozygous for the p.Q387X mutation. In the course of the follow-up time of 4-29 years, progression of existing and appearance of new symptoms developed. Although severe, many of these symptoms presented in all six young adult patients are often overlooked or neglected: postural hypotension with blurred vision and syncope, hyposalivation resulting with complete edentulosis, talocrular contractures with permanent walking difficulties and erectile dysfunction in male patients. Triple A syndrome is a progressive debilitating disorder which may seriously affect quality of life and even be life-threatening in patients with severe neurological impairment. Long-term follow-up of patients with triple A syndrome revealed a variety of the clinical features involving many systems. Progressive natural course of the disease may seriously affect quality of life and even be life-threatening in patients with severe neurological impairment.


Gynaecothelia--a common yet ignored sign of multibacillary leprosy in males: a case series with review of literature.
Leprosy is one of the causes of gynaecothelia (enlargement of nipples), however little has been published about this common but usually ignored sign. Herein, we report nine male patients with multibacillary leprosy who had gynaecothelia although only two of them had associated gynaecomastia. None of these patients was aware of gynaecothelia until it was detected by the treating doctor during examination. This study is presented to highlight this common but ignored sign, which may occur specifically in multibacillary leprosy.


From the Bay of Naples to the River Don: the Campanian Ignimbrite eruption and the Middle to Upper Paleolithic transition in Eastern Europe.
The Campanian Ignimbrite (CI) eruption, dated by 40Ar/39Ar and various stratigraphic methods to ca. 39,000 cal BP, generated a massive ash plume from its source in southern Italy across Southeastern and Eastern Europe. At the Kostenki-Borshchevo open-air sites on the Middle Don River in Russia, Upper Paleolithic artifact assemblages are buried below, within, and above the CI tephra (which is redeposited by slope action at most sites) on the second terrace. Luminescence and radiocarbon dating, paleomagnetism, and soil and pollen stratigraphy provide further basis for correlation with the Greenland and North Atlantic climate stratigraphy. The oldest Upper Paleolithic occupation layers at Kostenki-Borshchevo may be broadly correlated with warm intervals that preceded the CI event and Heinrich Event 4 (HE4; Greenland Interstadial: GI 12-GI 9) dating to ca. 45,000-41,000 cal BP. These layers contain an industry not currently recognized in other parts of Europe. Early Upper Paleolithic layers above the CI tephra are correlated with HE4 and warm intervals that occurred during 38,000-30,000 cal BP (GI 8-GI 5), and include an assemblage that is assigned to the Aurigancian industry, associated with skeletal remains of modern humans.


Non-coding RNAs: Functions and applications in endocrine-related cancer.
A significant fraction of the human genome is transcribed as non-coding RNAs (ncRNAs). This non-coding transcriptome has challenged the notion of the central dogma and its involvement in transcriptional and post-transcriptional regulation of gene expression is well established. Interestingly, several ncRNAs are dysregulated in cancer and current non-coding transcriptome research aims to use our increasing knowledge of these ncRNAs for the development of cancer biomarkers and anti-cancer drugs. In endocrine-related cancers, for which survival rates can be relatively low, there is a need for such advancements. In this review, we aimed to summarize the roles and clinical implications of recently discovered ncRNAs, including long ncRNAs, PIWI-interacting RNAs, tRNA- and Y RNA-derived ncRNAs, and small nucleolar RNAs, in endocrine-related cancers affecting both sexes. We focus on recent studies highlighting discoveries in ncRNA biology and expression in cancer, and conclude with a discussion on the challenges and future directions, including clinical application. ncRNAs show great promise as diagnostic tools and therapeutic targets, but further work is necessary to realize the potential of these unconventional transcripts.


Belt-induced abdominal injuries in recent frontal impact CIREN cases.
The objective is to report sex-related variation in 3-point belt-related abdominal injuries in Crash Injury Research Engineering Network (CIREN) cases. A query of CIREN cases was made for those with the highest ranked Collision Deformation Classification (CDC) to the front plane, a principal direction of force (PDOF) ±20° from 0°, and Abbreviated Injury Scale (AIS) 2+ abdomen injuries attributed to the seat belt. Patterns of injury were categorized as above the crest of the ilium, injuries below the crest of the ilium, and injuries above and below the ilium. This was done in the context of autonomous vehicle occupant kinematics testing results. Twelve 5th and 95th percentile 3-point belt-restrained postmortem human subjects were subjects; test speeds and recline angles varied. Abdomen injuries were anticipated; none were observed. Thirty-five occupants with belt-related abdominal injuries were identified. Seventeen case occupants sustained an injury only within the pelvic contents: 5 women and 12 men. Nine of the 17 were at or above the 81st percentile for height, 13 were between the 62nd and 80th percentile for height, and 4 were less than the 50th percentile for height. The stature component of the body mass index (BMI) appears to be a plausible candidate for an independent variable that is a contributing factor explaining the incidence of pelvic contents injuries when a 3-point belt-restrained occupant is involved in a frontal impact.


Hippocampal synaptoproteomic changes of susceptibility and resilience of male rats to chronic social isolation.
The susceptibility of an individual to chronic social isolation (CSIS) stress may cause major depression (MD) whereby some individuals are resistant to the stress. Recent studies relate MD with altered expression of synaptic proteins in specific brain regions. To explore the neurobiological underpinnings and identify candidate biomarkers of susceptibility or resilience to CSIS, a comparative proteomic approach was used to map hippocampal synaptic protein alterations of rats exposed to 6 weeks of CSIS, an animal model of depression. This model generates two stress-response phenotypes: CSIS-sensitive (depressive-like behaviour) and CSIS-resilience assessed by means of sucrose preference and forced swim tests. Our aim was to characterize the synaptoproteome changes representative of potential long-term changes in protein expression underlying susceptibility or resilience to stress. Proteomic data showed increased expression of glycolytic enzymes, the energy-related mitochondrial proteins, actin cytoskeleton, signalling transduction and synaptic transmission proteins in CSIS-sensitive rats. Protein levels of glutamate-related enzymes such as glutamate dehydrogenase and glutamine synthetase were also increased. CSIS-resilient rats showed similar proteome changes, however with a weaker increase compared to CSIS-sensitive rats. The main difference was observed in the level of protein expression of vesicle-mediated transport proteins. Nonetheless, only few proteins were uniquely up-regulated in the CSIS-resilient rats, whereby Cytochrome b-c1 complex subunit 2, mitochondrial (Uqcrc2) and Voltage-dependent anion-selective channel protein 1 (Vdac1) were uniquely down-regulated. Identified altered activated pathways and potential protein biomarkers may help us better understand the molecular mechanisms underlying synaptic neurotransmission in MD or resilience, crucial for development of new therapeutics.


Gender identity, gender assignment and reassignment in individuals with disorders of sex development: a major of dilemma.
Disorders of Sex Development (DSD) are a wide range of congenital conditions characterized by an incongruence of components involved in sexual differentiation, including gender psychosexual development. The management of such disorders is complex, and one of the most crucial decision is represented by gender assignment. In fact, the primary goal in DSD is to have a gender assignment consistent with the underlying gender identity in order to prevent the distress related to a forthcoming Gender Dysphoria. Historically, gender assignment was based essentially on surgical outcomes, assuming the neutrality of gender identity at birth. This policy has been challenged in the past decade refocusing on the importance of prenatal and postnatal hormonal and genetic influences on psychosexual development. (1) to update the main psychological and medical issues that surround DSD, in particular regarding gender identity and gender assignment; (2) to report specific clinical recommendations according to the different diagnosis. A systematic search of published evidence was performed using Medline (from 1972 to March 2016). Review of the relevant literature and recommendations was based on authors' expertise. A review of gender identity and assignment in DSD is provided as well as clinical recommendations for the management of individuals with DSD. Given the complexity of this management, DSD individuals and their families need to be supported by a specialized multidisciplinary team, which has been universally recognized as the best practice for intersexual conditions. In case of juvenile GD in DSD, the prescription of gonadotropin-releasing hormone analogues, following the World Professional Association for Transgender Health and the Endocrine Society guidelines, should be considered. It should always be taken into account that every DSD person is unique and has to be treated with individualized care. In this perspective, international registries are crucial to improve the understanding of these challenging conditions and clinical practice, in providing a better prediction of gender identity.


[Problem solving of the clinical case-method type for the development of clinical thinking. The illustrative problem of galactosemia].
Problem-solving case approach is an effective method for teaching clinical concepts. This method makes medical students be aware of the significance of Biochemistry for the clinical practice. The students are stimulated to study basic biochemical principles. The complete text of a problem case on galactosemia is presented. This case, usually given to the students during the final seminar on carbohydrate metabolism reflects a real situation, in which the student feels responsible to make decisions. He has to make the diagnosis and prescribe a treatment. The student's actions are assessed and commented. The students took a great interest in that problem case and that shows that it is possible and necessary even in the second preclinical year to joint the theoretical principles with the future clinical practice.


Toxicity of antirheumatic and anti-inflammatory drugs in children.
The aim of the study was to describe the long-term toxicity of antirheumatic and anti-inflammatory drugs in a paediatric rheumatology clinic population. One hundred and seventeen children were studied on first admission to a paediatric rheumatology clinic and after a mean of 8.6 +/- 0.4 years of follow-up. Medical records from the intermediate period were reviewed. The patients had 155 exposures to non-steroidal anti-inflammatory drugs (NSAIDs), 88 exposures to disease-modifying antirheumatic drugs (DMARDs) and 12 exposures of prednisolone during a total of 682 patient years. Drug toxicity was measured in terms of the number of toxic events, number of drug discontinuations due to toxicity, number of side-effects per patient year of drug exposure and as a toxicity index. Side-effects were seen in 69 (27%) of the drug exposures, corresponding to 0.10 toxic events per patient year of exposure. Abdominal pain was the most common side-effect, and was reported in 21 (14%) of the exposures to NSAIDs. Five severely toxic events, all leading to hospitalisation, occurred. The toxicity of NSAIDs was not significantly different from that of DMARDs with regard to the number of toxic events (21% and 31%, respectively, NS) and drug discontinuations due to toxicity (17% and 14%, respectively, NS). Piroxicam tended to be more toxic than ibuprofen (46% versus 18% toxic events, p <0.05; 36% versus 16% discontinuations due to toxicity, NS; 0.33 versus 0.05 side-effects per patient year and a toxicity index of 1.45 versus 0.20 units per patient year). Gold tended to be more toxic than antimalarials (41% versus 15% toxic events, p<0.05; 24% versus 12% discontinuations, NS; 0.37 versus 0.08 side-effects per patient year and a toxicity index of 1.56 versus 0.23 units per patient year). It was concluded that antirheumatic and anti-inflammatory drugs led to side-effects in 27% of the exposed children during 9 years of follow-up. There was an overlap of the toxicity of certain NSAIDs and the most commonly employed DMARDs.


The effect of 6-mercaptopurine on natural killer-cell activities in Crohn's disease.
Crohn's disease patients on long-term 6-mercaptopurine therapy (more than 4 months) were evaluated for activity of peripheral blood natural killer cells. Natural killer-cell cytolytic activity against K-562 tumor-cell targets was examined, as was natural killer-cell suppression of lymphoblastoid B-cell antibody production. In addition, these patients were studied for their ability to generate antitetanus-specific IgG-antibody-producing lymphoblastoid B cells following in vivo booster immunization. Crohn's disease patients on 6-mercaptopurine therapy had significant reductions in peripheral blood natural killer-cell activity against K-562 targets compared to normals, disease controls, and Crohn's disease patients not on 6-mercaptopurine. Natural killer-cell suppression of lymphoblastoid B-cell antibody production was likewise decreased in 6-mercaptopurine-treated patients compared to normal controls. In contrast, the in vivo generated lymphoblastoid B-cell antibody responses of Crohn's disease patients on 6-mercaptopurine therapy were not decreased compared to normal, while Crohn's disease patients not on 6-mercaptopurine therapy had significantly impaired IgG antitetanus antibody responses. These findings suggest that 6-mercaptopurine therapy in Crohn's disease affects several lymphoid subpopulations, resulting in a decreased natural killer-cell cytotoxic activity against K-562 target cells and a decreased natural killer-cell ability to suppress lymphoblastoid B-cell antibody production, as well as an improved humoral immune response following tetanus toxoid booster immunization.


Differences in three intercondylar notch geometry indices between males and females: a cadaver study.
The primary purpose of this unique evaluation of cadaveric skeletal geometry was to compare intercondylar notch geometry between males and females. One hundred male skeletons and 100 female skeletons were evaluated. Three indices of notch geometry were calculated from digital photographs of the distal femur: notch width index, notch area index, and notch shape index. Notch shape index for males exceeded that for females (P<0.004). The intercondylar notch appears less round in females and may play a role in causing ACL injuries. Future studies are required to confirm any link between notch geometry and ACL injury.


Effects of selection delays on radial maze performance: acquisition and effects of scopolamine.
The effects of post-selection confinement (delays) on both the acquisition of performance and the response to the muscarinic blocker, scopolamine, were examined in an automated version of the eight arm radial maze. Long-Evans rats, exposed to post-selection delays of 0.5 sec (n = 4) or 100 sec (n = 4) during daily training trials did not differ in either the number of trials to acquire an accurate baseline of performance or in the amount of time required to obtain all eight food pellets. However, the pattern (delta-arm scores) of within-session arm selections demonstrated by the two groups of rats differed. Rats exposed to the 0.5-sec delay typically selected arms adjacent to arms from which they exited while rats exposed to the 100-sec delay were more likely to enter arms 2-removed from the exit arm. When scopolamine (0.03 to 1.0 mg/kg) was administered prior to testing, rats in the 100-sec delay group showed a greater reduction of accuracy and a larger increase in selection latency than rats in the 0.5-sec delay group. The differential effect of delay value on delta-arm scores was also eliminated in a dosage dependent manner with scopolamine. Scopolamine methylbromide (0.3 mg/kg) was found to have little effect on performance. In summary, the results indicate that the post-selection delay procedure is a sensitive and selective test for chemical-induced dysfunctioning of spatial memory in rats.


Suppression of cytotoxic and proliferative xenogeneic T-cell responses by transgenic expression of indoleamine 2,3-dioxygenase.
Tryptophan catabolism initiated by the enzyme indoleamine 2,3-dioxygenase (IDO) has been postulated to be a natural regulatory mechanism for T cells. In this study, we generated a pig endothelial cell line expressing full-length human IDO (P-HuIDO) to serve as a simple model of a cellular xenogeneic graft. Splenocytes from mice primed to P-HuIDO cells were found to be as responsive to secondary stimulation as splenocytes from mice primed to parental cells. However, in T-cell proliferation assays using P-HuIDO cells as stimulators, a significant inhibition of both naive and memory xenogeneic proliferative responses was noted. Furthermore, the production of interferon-gamma and cytotoxic T lymphocyte function were also affected. When severe combined immunodeficiency mice were grafted with P-HuIDO cells, then challenged with primed splenocytes from BALB/c mice, cellular infiltration to the graft was delayed. Our findings suggest that transgenic expression of IDO in xenografts contributes to prolonged graft survival.


PeroxiBase: a database with new tools for peroxidase family classification.
Peroxidases (EC 1.11.1.x), which are encoded by small or large multigenic families, are involved in several important physiological and developmental processes. They use various peroxides as electron acceptors to catalyse a number of oxidative reactions and are present in almost all living organisms. We have created a peroxidase database (http://peroxibase.isb-sib.ch) that contains all identified peroxidase-encoding sequences (about 6000 sequences in 940 organisms). They are distributed between 11 superfamilies and about 60 subfamilies. All the sequences have been individually annotated and checked. PeroxiBase can be consulted using six major interlink sections 'Classes', 'Organisms', 'Cellular localisations', 'Inducers', 'Repressors' and 'Tissue types'. General documentation on peroxidases and PeroxiBase is accessible in the 'Documents' section containing 'Introduction', 'Class description', 'Publications' and 'Links'. In addition to the database, we have developed a tool to classify peroxidases based on the PROSITE profile methodology. To improve their specificity and to prevent overlaps between closely related subfamilies the profiles were built using a new strategy based on the silencing of residues. This new profile construction method and its discriminatory capacity have been tested and validated using the different peroxidase families and subfamilies present in the database. The peroxidase classification tool called PeroxiScan is accessible at the following address: http://peroxibase.isb-sib.ch/peroxiscan.php.


Gap junctional communication and compaction during preimplantation stages of mouse development.
The ability of gap junction antibodies to block dye transfer and electrical coupling was examined in the compacted 8-cell mouse zygote. In control zygotes, Lucifer yellow injected into 1 cell transferred to the rest of the embryo. When antibodies raised against the major protein extracted from gap junctions were co-injected with Lucifer yellow, dye transfer failed in 86% of the zygotes tested and electrical coupling was almost completely inhibited. Subsequently, the antibody-containing cells were extruded. When the antibodies were injected into 1 cell at the 2-cell stage, 82% of the zygotes divided normally to the 8-cell stage. Cells containing gap junction antibodies were uncompacted, but continued to divide. We conclude that these antibodies inhibit gap junctional communication in the early mouse zygote and that communication through gap junctions may be involved in the maintenance of compaction.


Ruptured aneurysm associated with a twig-like middle cerebral artery: An illustrative case report.
Anomalies of the middle cerebral artery (MCA) are rare; among the different types of anomalies, the aplastic or twig-like (Ap/T) MCA is extremely rare and has been reported under various names, including aplastic, unfused, or rete type anomaly. The occurrence of a brain aneurysm associated with this anatomic variant is an even rare event, and probably their development and rupture are related to hemodynamic stress of the tinny wall of vessels forming the network. We present a 43-year-old male patient with an explosive and persistent right orbitofrontal headache. A computed tomography showed a right frontobasal hematoma with intraventricular disruption. Magnetic resonance angiography showed a right MCA aneurysm and what seems to be a MCA trunk stenosis. Cerebral digital subtraction angiography demonstrated a plexiform arterial network and one aneurysm arising from the network. The patient was successfully treated by surgical clipping to evacuate the hematoma and to prevent further intracranial hemorrhages. The Ap/T-MCA may be associated with hemodynamic stress with a significant effect through the tinny wall of the vessels causing hemorrhage or leading to the formation and rupture of cerebral aneurysms. Based on a correct diagnosis of the anomaly, treatment can be completed successfully through different standard methods.


Pseudo-tumoral renal actinomycosis.
Actinomycosis is a rare granulomatous chronic infection that is localized most frequently in the cranio-cervical region. Renal localization is exceptional. The authors report a new case of pseudo-tumoral actinomycosis and discuss diagnostic and treatment issues of this disease.


Short-Term Outcomes following Virtual Surgery-Assisted Immediate Dental Implant Placement in Free Fibula Flaps for Oncologic Mandibular Reconstruction.
Despite reports demonstrating feasibility of immediate dental implant placement in mandibular reconstruction with free fibula flaps for benign disease, this practice is not routinely used in the oncologic setting. The authors aim to demonstrate the safety of immediate dental implant placement for oncologic mandible reconstruction. In 2017, the authors' center began immediate dental implant placement in free fibula flaps for oncologic patients undergoing mandibulectomy reconstruction. Immediate dental implant placement patients were compared to a historical cohort also reconstructed with computer-aided design and manufacturing technology beginning in 2011 (n = 34) as a noninferiority study design. Primary outcomes of interest included 90-day complications, time to radiotherapy, and time to and number of patients achieving dental restoration. Sixty-one patients underwent free fibula flaps following mandibulectomy using computer-aided design and manufacturing. Seventy-two dental implants were placed in the immediate dental implant placement cohort (n = 27). No differences were noted in major or minor 90-day complications between groups (p > 0.05). Radiotherapy was required in 55 percent in the immediate dental implant placement cohort versus 62 percent in the historical cohort, with no significant difference in time to radiotherapy (67.6 days versus 62.2 days, respectively). One dental implant was removed for nonosseointegration noted during vestibuloplasty. Fourteen (51.8 percent) immediate dental implant patients had complete dental restoration at 90 days compared with none in the historical cohort (p < 0.05). Immediate dental implant placement is a safe procedure with an unchanged short-term complication profile and no delay in radiotherapy initiation. Patients undergoing immediate dental implant placement are more likely to complete full dental rehabilitation. Long-term and health-related quality-of-life outcomes remain to be determined. Therapeutic, III.


Continuous-wave ultrasound and neoplastic transformation in vitro.
C3H/10T1/2 cells in suspension were assayed using an initiation-promotion protocol for neoplastic transformation induced by continuous-wave ultrasound. Cells were insonated at 1.765 MHz for 40 min. Two ultrasonic intensities were used: 1.3 and 2.6 W/cm2 spatial average. The first intensity was found to be noncytotoxic; the second resulted in immediate lysis of 20% of the cells, followed by the clonogenic survival of 64% of the remaining cells. Ultrasound was delivered alone or in combination with X-rays (2 Gy, 240 kVp given before ultrasound), and/or 12-O-tetradecanoyl-phorbol-13-acetate (TPA, 0.1 microgram/ml post-irradiation). Under all treatment conditions, there was no effect of ultrasound on transformation at the 95% confidence level.


Granulocyte-colony stimulating factor ameliorates irradiation-induced suppression of hippocampal neurogenesis in adult mice.
Granulocyte-colony stimulating factor (G-csf) is a member of the hematopoietic growth factor family and demonstrates neuroprotective functions in neurodegenerative diseases. This study evaluated the radioprotective effects of G-csf in the suppression of hippocampal neurogenesis in adult mice undergoing irradiation. The radioprotective effects were assessed using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and immunohistochemical markers of neurogenesis, including the proliferating cell marker Ki-67 and the immature progenitor neuron marker doublecortin (DCX). Acute exposure to cranial irradiation (5Gy γ-rays) induced neural apoptosis and inhibited neurogenesis in the dentate gyrus (DG) of the adult mouse hippocampus. Pretreatment with G-csf (100μg/kg every 12h subcutaneously on three consecutive days) attenuated neural apoptosis and decreased the number of Ki-67- and DCX-positive cells in the DG of the irradiated mouse hippocampus. Therefore, G-csf inhibited the detrimental effects of irradiation on hippocampal neurogenesis, suggesting that G-csf administration has potential therapeutic utility in brain irradiation.


[On the family placement at the service of family therapy: 150 years of Medical-psychological annals].
The historic of families colony (Geel in Belgium) brought a great debate in the "Annales Medico-Psychologiques", 150 years ago. The controversy stay very actual between hospitalocentrisme orientation and deinstitutionalization movement. The economic motivations influence very often on the final orientation of the mental health system.