Interrelation between tumor-associated cell surface glycoprotein and host immune response in gastric carcinoma patients.
Expression of changes in cell surface glycoprotein may correlate with the malignant potential and development of gastric carcinoma. Immunologic defense mechanisms of the host against the tumor can be effective in preventing the development of gastric carcinoma. The authors studied the effects of immunologic defense of the host against the tumor, using infiltration of S-100 protein positive dendritic cells (DC) as a marker. In cases with or without changes in the surface glycoprotein of tumor cells, determinations were made by binding of Helix pomatia agglutinin (HPA). Paraffin blocks of 123 gastric carcinoma specimens were prepared for immunohistochemical staining with the antibody against HPA and S-100 protein. Clinicopathologic factors and patient prognosis were examined for each indicator. Patients with HPA positive tumors had a more aggressive character in several important prognostic aspects and poorer 5-year survival rates compared with patients with HPA negative tumors. The degree of infiltration of DC had no particular correlation with pathologic factors, and there was no significant difference between the prognosis of patients with slight and marked DC infiltration. In the HPA negative patients there was no significant difference in the 5-year survival rates between patients with slight and marked DC infiltration; however, in the HPA positive patients the 5-year survival rates of patients with marked infiltration of DC were higher. Further investigation showed that patients with marked DC infiltration had better 5-year survival rates than patients with slight DC infiltration, especially in patients with HPA positive and histologically advanced disease. Patients with a higher immunologic defense against cancer cells, as indicated by marked infiltration of DC, had a better prognosis in cases of gastric carcinomas of highly malignant potential, as indicated by a positive HPA.


Human Olfactory Bulb Neural Stem Cells (Hu-OBNSCs) Can Be Loaded with Paclitaxel and Used to Inhibit Glioblastoma Cell Growth.
Exploitation of the potential ability of human olfactory bulb (hOB) cells to carry, release, and deliver an effective, targeted anticancer therapy within the central nervous system (CNS) milieu remains elusive. Previous studies have demonstrated the marked ability of several types of stem cells (such as mesenchymal stem cells (MSCs) to carry and release different anti-cancer agents such as paclitaxel (PTX). Herein we investigate the ability of human olfactory bulb neural stem cells (Hu-OBNSCs) to carry and release paclitaxel, producing effective cytotoxic effects against cancer cells. We isolated Hu-OBNSCs from the hOB, uploaded them with PTX, and studied their potential cytotoxic effects against cancer cells in vitro. Interestingly, the Hu-OBNSCs displayed a five-fold increase in their resistance to the cytotoxicity of PTX, and the PTX-uploaded Hu-OBNSCs were able to inhibit proliferation and invasion, and to trigger marked cytotoxic effects on glioblastoma multiforme (GBM) cancer cells, and Human Caucasian fetal pancreatic adenocarcinoma 1 (CFPAC-1) in vitro. Despite their ability to resist the cytotoxic activity of PTX, the mechanism by which Hu-OBNSCs acquire resistance to PTX is not yet explained. Collectively our data indicate the ability of the Hu-OBNSCs to resist PTX, and to trigger effective cytotoxic effects against GBM cancer cells and CFPAC-1. This indicates their potential to be used as a carrier/vehicle for targeted anti-cancer therapy within the CNS.


Influence of vision on upper limb reaching movements in patients with cerebellar ataxia.
The effects of vision on spatial and temporal characteristics of free unrestrained reaching movements of the arm were examined in 17 patients with ataxic syndromes due to degenerative disease of the cerebellum and its connections. Subjects were required to reach out and touch a visually presented target either in the dark or with the target and their finger visible. Overall, patients had prolonged reaction times and their movements were performed slower than normal. The spatial paths described by their fingertips were more circuitous, being of greater length than normal, a characteristic that was uninfluenced by visual conditions. Ataxic movements were less accurate than normal in two ways. First, there was greater spatial variability between repeat paths to the same target. The increased variability was present very early in the movement trajectory and at that stage was not influenced by visual feedback. Secondly, there were large constant errors at the end of movement, but only when moving in darkness. Patients with Friedreich's ataxia as well as those with intrinsic cerebellar degeneration showed the above abnormalities, although there were some quantitative differences between the two groups. We suggest these spatial errors arise because the cerebellum contributes either directly or indirectly to preparatory motor processes which, based on limb proprioceptive and retinal information, compute the pattern of muscle activity required to launch the limb accurately towards a target. Patients were largely successful at using visual guidance to make midflight adjustments to their movements in order to improve accuracy. This manifested as a reduction in spatial variability between repeat paths as the target was approached and a reduction in constant error. However, the visual correction mechanism did not appear normal. Under visual guidance, the end-phase of movement was often prolonged and characterized by excessive deviations or direction changes in the path. These deviations may be the expression of a visual guidance system producing corrections which themselves contain error requiring further correction. Thus, this process may be abnormal for the same reason that the initial pattern of muscle activity is misjudged.


In Vitro Differentiation of Human Pluripotent Stem Cells into Trophoblastic Cells.
The placenta is the first organ to develop during embryogenesis and is required for the survival of the developing embryo. The placenta is comprised of various trophoblastic cells that differentiate from the extra-embryonic trophectoderm cells of the preimplantation blastocyst. As such, our understanding of the early differentiation events of the human placenta is limited because of ethical and legal restrictions on the isolation and manipulation of human embryogenesis. Human pluripotent stem cells (hPSCs) are a robust model system for investigating human development and can also be differentiated in vitro into trophoblastic cells that express markers of the various trophoblast cell types. Here, we present a detailed protocol for differentiating hPSCs into trophoblastic cells using bone morphogenic protein 4 and inhibitors of the Activin/Nodal signaling pathways. This protocol generates various trophoblast cell types that can be transfected with siRNAs for investigating loss-of-function phenotypes or can be infected with pathogens. Additionally, hPSCs can be genetically modified and then differentiated into trophoblast progenitors for gain-of-function analyses. This in vitro differentiation method for generating human trophoblasts starting from hPSCs overcomes the ethical and legal restrictions of working with early human embryos, and this system can be used for a variety of applications, including drug discovery and stem cell research.


[Changes in the direction of vestibulomotor responses in the process of adaptation to prolonged static head turning in man].
Vestibulomotor responses were studied in normal blindfold subjects in the upright posture during adaptation to maintaining the head turned to the left up to the extreme position for 10 min. The head was maintained in that position either passively or actively. In 5 out of 12 subjects tested, adaptation to the unusual head position resulted in a gradual decrease of the appreciated angle of the head position. The error in appreciating the head position reached as much as 70-80 degrees. The direction of the vestibulomotor response was found to change in parallel with the appreciated head orientation. Thus, under mismatch between the perceived and actual head positions the direction of the vestibulomotor response corresponded to the spatial perception rather than to the actual head orientation.


[Treating avascular necrosis of femoral head in young adult by grafting sartorius muscle iliac bone flap].
To explore an improved method of treating avascular necrosis of the femoral head in young adults by grafting the sartorius muscle iliac bone flap. From September 1994 to August 2003, 68 patients (57 males, 11 females; age, 16-58 years) underwent of the transplant the sartorius muscle oliac bone flap into the femoral head after decompression of the femoral head medullary core and removal of the dead bone and the fibrous tissue in the femoral head. The transplantation was performed on 31 patients left-unilaterally, on 37 patients right-unilaterally, and on 7 patients bilaterally. The pathological causes were as follows: alcoholism in 52 patients, prolonged use of hormones in 6, trauma in the hip in 6, and undetermined cause in 4. Their illness course ranged from 8 months to 4 years. According the Ficat staging, 10 patients belonged to Stage I (11 sides), 27 patients to Stage II (31 sides), and 31 patients to Stage III (33 sides). The follow-up of the 68 patients for 2. 5-11 years averaged 5. 2 years revealed that based on the Harris evaluation for the hip function, 23 patients had an excellent result, 33 had a good result, 10 had a fair result, and 2 had a poor result. The excellent and good results accounted for 82.3%. There was no recurrence after operation. This method has the following advantages: the lesion focus can be eradicated; enough decompression can be achieved, and the blood circulation for the femoral head can be rebuilt. The grafting of the sartorius muscle iliac bone flap can bring the osteogenesis components to the femoral head, promoting the reconstruction of the bones. This method is suitable and effective for the patients with avascular necrosis of the femoral head (Ficat Grades I, II and III) in young adults.


PDL and CD insensitive low complexity equalizer for short reach coherent systems.
We propose a polarization dependent loss (PDL) and chromatic dispersion (CD) insensitive, low-complexity adaptive equalizer (AEQ) for short-reach coherent optical transmission systems. The AEQ contains a 1-tap butterfly finite impulse response (FIR) filter and two N-tap FIR filters. It first performs polarization demultiplexing using the 1-tap filter, of which the coefficients are obtained based on Stokes space. Then it mitigates the inter-symbol interference (ISI) using the two N-tap finite impulse response (FIR) filters and adjust the filter's coefficients by utilizing constant modulus algorithm (CMA). Through theoretical and experimental analysis, we verify that this proposed AEQ can perform robust polarization demultiplexing when PDL and CD exists. Besides, our proposed AEQ has faster convergence speed compared with recently proposed AEQs. In addition, it reduces the number of multipliers and thus reduce the computational complexity of conventional butterfly filter structure AEQ. And this proposed AEQ suffers little bit error ratio loss compared with the conventional AEQ. Due to the low-complexity and robustness to PDL and CD, this proposed AEQ is well-suited for future low-cost short-reach optical communication system.


Effects of DMSO, glycerol, betaine and their combinations in detecting single nucleotide polymorphisms of epidermal growth factor receptor (EGFR) gene promoter sequence in non-small-cell lung cancer (NSCLC) patients.
The aim of the study was to examine the effects of frequently used polymerase chain reaction (PCR) additives DMSO, glycerol and betaine on amplification of GC-rich epidermal growth factor receptor (EGFR) gene promoter region, in order to detect the presence of -216G>T and -191C>A gene variations in non-small-cell lung cancer (NSCLC) patients. PCR products and restriction fragments were detected by electrophoresis on 8% polyacrylamide gel and 3% agarose gel. Our analysis shows that single used additives including DMSO in concentration of 7% and 10%, glycerol in concentration of 10%, 15% and 20%, as well as betaine in concentration of 1M, 1.5M and 2M significantly enhanced the yield and specificity of PCR reaction. In addition, the combination of 10% DMSO with 15% glycerol has shown positive effects, whereas other analyzed combinations of additives failed to amplify the EGFR promoter region.


p38 mitogen-activated protein kinase is critical for synergistic induction of the FSH(beta) gene by gonadotropin-releasing hormone and activin through augmentation of c-Fos induction and Smad phosphorylation.
GnRH and activin independently and synergistically activate transcription of the FSH beta-subunit gene, the subunit that provides specificity and is the limiting factor in the synthesis of the mature hormone. This synergistic interaction, as determined by two-way ANOVA, is specific for FSHbeta and may, therefore, contribute to differential expression of the two gonadotropin hormones, which is critical for the reproductive cycle. We find that the cross-talk between the GnRH and activin signaling pathways occurs at the level of p38 MAPK, because the synergy is dependent on p38 MAPK activity, which is activated by GnRH, and activin cotreatment augments p38 activation by GnRH. Both the Smad and activator protein-1 binding sites on the FSHbeta promoter are necessary and sufficient for synergy. After cotreatment, Smad 3 proteins are more highly phosphorylated on the activin-receptor signaling-dependent residues on the C terminus than with activin treatment alone, and c-Fos is more highly expressed than with GnRH treatment alone. Inhibition of p38 by either of two different inhibitors or a dominant-negative p38 kinase abrogates synergy on FSHbeta expression, reduces c-Fos induction by GnRH, and prevents the further increase in c-Fos levels that occurs with cotreatment. Additionally, p38 is necessary for maximal Smad 3 C-terminal phosphorylation by activin treatment alone and for the further increase caused by cotreatment. Thus, p38 is the pivotal signaling molecule that integrates GnRH and activin interaction on the FSHbeta promoter through higher induction of c-Fos and elevated Smad phosphorylation.


Cytotoxicity of low pH dentin-bonding agents in a dentin barrier test in vitro.
The reaction of three-dimensional cultures of pulp-derived cells in a dentin barrier test was recorded after exposure to All-Bond 2, Prime & Bond NT, Syntac SC, Syntac Classic, and Prompt L-Pop. The materials were applied on bovine dentin disks in a perfusion chamber, and the experiments were performed with (0.3 ml/h, 2 ml/h) and without perfusion of the pulpal part of the chamber. The cell reaction was recorded (MTT assay) and related to noncytotoxic controls. Bonding agents with low pH did not show any cytotoxicity. Syntac Classic decreased the cell activities to 38% to 72%, depending on different experimental conditions, and was more cytotoxic than Syntac SC. Perfusion (2 ml/h) reduced the cytotoxicity for Syntac Classic and increased cell activities from 52% to 72%. Because low pH bonding agents did not show toxic reactions in this dentin barrier test, pulp damage caused by the tested substance is unlikely if a dentin layer protects the pulp.


Engineering the ribosomal DNA in a megabase synthetic chromosome.
We designed and synthesized a 976,067-base pair linear chromosome, synXII, based on native chromosome XII in Saccharomyces cerevisiae SynXII was assembled using a two-step method, specified by successive megachunk integration and meiotic recombination-mediated assembly, producing a functional chromosome in S. cerevisiae. Minor growth defect "bugs" detected in synXII, caused by deletion of tRNA genes, were rescued by introducing an ectopic copy of a single tRNA gene. The ribosomal gene cluster (rDNA) on synXII was left intact during the assembly process and subsequently replaced by a modified rDNA unit used to regenerate rDNA at three distinct chromosomal locations. The signature sequences within rDNA, which can be used to determine species identity, were swapped to generate a Saccharomyces synXII strain that would be identified as Saccharomyces bayanus by standard DNA barcoding procedures.


Crossed renal ectopia with colic. A clinical clue to embryogenesis.
A clinicopathologic correlation of 2 patients with crossed renal ectopia presenting with ureteric colic and 4 cases collected from the literature is presented. The correlation serves to reaffirm the theory of ureteral and not renal, migration as the primary aberration resulting in this defect.


The multiple gene duplication problem revisited.
Deciphering the location of gene duplications and multiple gene duplication episodes on the Tree of Life is fundamental to understanding the way gene families and genomes evolve. The multiple gene duplication problem provides a framework for placing gene duplication events onto nodes of a given species tree, and detecting episodes of multiple gene duplication. One version of the multiple gene duplication problem was defined by Guigó et al. in 1996. Several heuristic solutions have since been proposed for this problem, but no exact algorithms were known. In this article we solve this longstanding open problem by providing the first exact and efficient solution. We also demonstrate the improvement offered by our algorithm over the best heuristic approaches, by applying it to several simulated as well as empirical datasets.


Lymphokine-activated killer (LAK) cells inhibit the clonogenic growth of human leukemic stem cells.
The effect of lymphokine-activated killer (LAK) cells on the in vitro clonogenic capacity of acute myeloid leukemia (AML) blasts was investigated in a semisolid medium assay. The leukemic clonogenic capacity of 11 AML cases, selected on the basis of their ability to grow in vitro, was highly reduced following overnight preincubation with LAK effectors. The degree of colony inhibition, which ranged between 66% and 98% (mean 83.8% +/- 11.4 SD), was quantitatively greater than by 51Cr release, which gave rise to lytic values between 5% and 65% (mean 43.2% +/- 19.2 SD). The demonstration that the clonogenic inhibition was still induced following a shorter pre-incubation period (4 hours) suggests that the effect is unlikely to be due only to the generation of cytotoxic activity during the incubation time. The possibility that LAK cells may be employed in the management of residual disease is strengthened by the evidence that the clonogenic potential of samples containing as few as 20% and 14.3% leukemic cells could be almost completely abolished by LAK effectors. These findings further point the possible role of adoptive immunotherapy with interleukin 2/LAK cells in the treatment of patients with acute leukemia.


High Selectivity and Sensitivity of Oligomeric p-Phenylene Ethynylenes for Detecting Fibrillar and Prefibrillar Amyloid Protein Aggregates.
Misfolding and aggregation of amyloid proteins into fibrillar aggregates is a central pathogenic event in neurodegenerative disorders such as Alzheimer's (AD) and Parkinson's diseases (PD). Currently, there is a lack of reliable sensors for detecting the range of protein aggregates involved in disease etiology, particularly the prefibrillar aggregate conformations that are more neurotoxic. In this study, the fluorescent sensing of two novel oligomeric p-phenylene ethynylenes (OPEs), anionic OPE1- and cationic OPE2+, for detecting prefibrillar and fibrillar aggregates of AD-associated amyloid-β (Aβ40 and Aβ42) and PD-associated α-synuclein proteins (wildtype, and single mutants A30P, E35K, and A53T) over their monomeric counterparts, were tested. Furthermore, the performance of OPEs was evaluated and compared to thioflavin T (ThT), the most widely used fibril dye. Our results show that OPE1- and OPE2+ exhibited aggregate-specific binding inducing large fluorescence turn-on and spectral shifts based on a combination of backbone planarization, hydrophobic unquenching, and superluminescent OPE complex formation sensing modes. OPEs exhibited higher selectivity, higher binding affinity, and comparable limits of detection for Aβ40 fibrils compared to ThT. OPE2+ exhibited the largest fluorescence turn-on and highest sensitivity. Significantly, OPEs detected prefibrillar aggregates of Aβ42 and α-synuclein that ThT failed to detect. The superior sensing performance, the nonprotein specific detection, and the ability to selectively detect fibrillar and prefibrillar amyloid protein aggregates point to the potential of OPEs to overcome the limitations of existing probes and promise significant advancement in the detection of the myriad of protein aggregates involved in the early stages of AD and PD.


The role of aortic chemoreceptors during acute anemia.
The importance of aortic chemoreceptors in the circulatory and metabolic responses during acute anemia was studied in anesthetized dogs. Data were obtained from nine dogs in which the aortic chemoreceptors were surgically denervated prior to induction of anemia, and from seven sham-operated dogs. Cardiac output (QT), limb blood flow (QL), limb and whole body oxygen uptake (VO2) were determined at normal hematocrit (Hct) and at 30 min of anemia (Hct = 13%) produced by isovolemic dextran-for-blood exchange. At 30 min of anemia, QT was increased from 91 to 186 mL . kg-1 . min-1 (p less than 0.01) and from 99 to 153 mL . kg-1 . min-1 (p less than 0.01) in the sham and denervated groups, respectively. The increase in QT during anemia was less (p less than 0.05) in the aortic-denervated series. Limb flow was also increased during anemia in both groups (p less than 0.01); the mean value of 89 mL . kg-1 . min-1 in the denervated group was less than that of 130 mL . kg-1 . min-1 observed in the sham animals (p less than 0.05). Whole body VO2 decreased (p less than 0.05) in the denervated group at 30 min of anemia; limb VO2 was maintained at the preanemic control value in both groups. The data indicate that during acute anemia the aortic chemoreceptors contribute to the increase in QT.


[Clostridium difficile in children and adolescents undergoing anticancer and antimicrobial chemotherapy. The possibility of nosocomial acquisition].
We looked for C. difficile and its cytotoxin among children and adolescents treated with diverse kinds of cancer chemotherapy in an oncologic ward of a pediatric hospital. Most of them were also given multiple antibiotic treatments, susceptible of making C. difficile colonization easier due to the modification of the intestinal ecosystem. As the colonization may have an external origin, we also looked for C. difficile in the environment. 14 patients have been studied and we found cytotoxic strains in four of them and non cytotoxic ones in two. This paper discusses the influence of cancer chemotherapy and antibiotherapy on C. difficile colonization among those patients, and the role played by this bacteria and its toxin on the diarrhea cycle. The facts that several patients have been colonized together and that environmental samples showed up positive, lead us to suspect a nosocomial spread. To confirm this thesis, strains originating from patients and environments were compared.


Tuberculosis and HIV: a partnership against the most vulnerable.
Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. Each year, there are eight million new Mycobacterium tuberculosis complex (MTB) infections and three million TB-related deaths. The catastrophic effects of TB are borne disproportionately among the most vulnerable. The HIV pandemic has further increased the burden so that the risk of TB reactivation from latency is 5 to 15 percent in HIV/TB coinfection. Tuberculosis reactivation fuels further primary infections, creating a vicious cycle of increasing infection, disease, and deaths. In addition, drug-resistant TB exacerbates this increasingly common problem. The clinical presentations of TB in relation to HIV and HIV-associated immune deficiency are discussed from the perspective of clinical diagnosis and treatment in patient care. Tuberculosis prophylaxis, concurrent drug treatment of TB and HIV, drug interactions, and overlapping toxicities are detailed for the practitioner. Immune reconstitution inflammatory reactions are now a common phenomenon in HIV treatment, where similar reactions have been less commonly described in TB treatment in the past. Global distributive injustices in wealth, the burden of disease, and the provision of healthcare are obvious in TB, and clearly show us that the needs of the most vulnerable populations must be met in order to address the problems.


An adaptive approach for heartbeat detection based on S-transform in seismocardiograms.
This study presents a new technique which allows identification of individual heartbeats from seismocardiograms (SCG) with high accuracy. Our method is electrocardiogram (ECG) independent and designed based upon S-transform and Shannon energy. The S-transform which is a time-frequency (TF) representation first provides frequency-dependent resolution while preserving a direct relationship with Fourier spectrum. Subsequently, individual heartbeats are detected in the time domain by calculating the Shannon energy (SSE) of each obtained local spectrum and employing other techniques such as successive mean quantization transform (SMQT) and adaptive thresholding. A total of 30 recordings were analysed in this study by measuring SCG and simultaneous electrocardiogram (ECG) in supine position. The performance of the algorithm was tested using the standard ECGs obtained from each test subject. The obtained results were as follows (sensitivity, precision, and detection error rate): (98.0%, 98.4% and 0.2%). In conclusion, the results confirmed that combination of S-transform, Shannon energy, and other techniques considerably enhanced the efficiency for the heartbeat detection in seismocardiograms.


Metalloporphines: Dimers and Trimers.
Procedures for the purification and subsequent crystallization of the slightly soluble four-coordinate metallporphines, the simplest possible porphyrin derivatives, are described. Crystals of the porphine derivatives of cobalt(II), copper(II), platinum(II), and two polymorphs of zinc(II) were obtained. Analysis of the crystal and molecular structures shows that all except the platinum(II) derivative form an unusual trimeric species in the solid state. The isomorphous cobalt(II), copper(II), and one zinc(II) polymorph pack in the unit cell to form dimers as well as the trimers. Interplanar spacings between porphine rings are similar in both the dimers and trimers and range between 3.24 and 3.37 Å. Porphine rings are strongly overlapped with lateral shifts between ring centers in both the dimers and trimers with values between 1.52 and 1.70 Å or in Category S as originally defined by Scheidt and Lee. Periodic trends in the M-Np bond distances parallel those observed previously for tetraphenyl- and octaethylporphyrin derivatives.


Ionic liquid marbles.
Liquid marbles have been reported during this decade and have been argued to be potentially useful for microfluidic and lab-on-a-chip applications. The liquid marbles described to date have been composed of either water or glycerol as the liquid and hydrophobized lycopodium or silica as the stabilizing particles. Both of these components are potentially reactive and do not permit the use of organic chemistry; the liquids are volatile. We report the use of perfluoroalkyl particles (oligomeric (OTFE) and polymeric (PTFE) tetrafluoroethylene, which are unreactive) to support/stabilize a range of ionic liquid marbles. Ionic liquids are not volatile and have been demonstrated to be versatile solvents for chemical transformations. Water marbles prepared with OTFE are much more robust than those prepared with hydrophobized lycopodium or silica.


Altered response to intravenous thiopental and succinylcholine in acute amphetamine abuse.
Substance abuse has become increasingly prevalent: illegal drugs have profound and varied physiologic effects which create a large potential for anesthetic problems and complications (1). Amphetamine is a strong sympathomimetic and may therefore influence the course of anesthesia. We report the case of a patient with acute amphetamine abuse presenting difficulties during anesthesia.


Molecular mechanisms and gene regulation of melphalan- and hyperthermia-induced apoptosis in Ewing sarcoma cells.
The prognosis of high-risk Ewing tumours (HR-ET) remains poor. Melphalan-containing chemotherapy regimens are commonly applied for HR-ET patients. Moreover, melphalan (Mel) is a promising agent in thermochemotherapy. Therefore, we investigated the single effects, the synergism and the gene regulation of Mel and hyperthermia (HT) in an ET cell line (RD-ES). Dose-dependent cytotoxicity by Mel was demonstrated, which was enhanced by the concomitant application of HT (42 degrees C for 2 h). Mel, HT and their combination caused a significant activation of caspase-3. Using the pan-caspase inhibitor z-VAD-fmk, we demonstrated that both stimuli mediated predominantly caspase-dependent cytotoxicity. With cDNA array analysis, 20 out of 198 apoptosis-related genes were identified to be differentially expressed by Mel and/or HT. Although a significant enhancement of three selected genes could not be proven at the protein level in subsequent experiments, this study gives insight into the complex molecular and genetic response of tumour cells to cytotoxic stimulation.


Controlling particle morphology and size in the synthesis of mesoporous SBA-15 materials.
Plate-like particles of SBA-15 form from smaller units (primary particles) that aggregate in an oriented manner. In this report we influence this aggregation by adding salt to the ongoing synthesis, generating well-ordered hexagonal p6m structure (SBA-15), with varying particle diameters. The additions, with either NaCl or NaI, were made at a time corresponding to the onset of oriented aggregation. Both salts promote the aggregation and particles with diameters of up to 5 microm were obtained. The thickness, about 0.4 microm, of the particles was retained, in accordance with the proposed growth mechanism. The aggregation characteristic was dependent on the salt used and the concentration of the salt. Both the cation and the anion were found to influence the aggregation. Having salt present already at the start of the synthesis gave a different product. The particle formation process depends on an interplay between attractive and repulsive forces between aggregates. We interpret the observed effect of salt addition to a medium which already has a very high ionic strength (1.6 M HCl) as due to ion binding to the combined polyethylene oxide-silica brush at the particles surface.


Spontaneous Mirror-Symmetry Breaking in Isotropic Liquid Phases of Photoisomerizable Achiral Molecules.
Spontaneous mirror-symmetry breaking is of fundamental importance in science as it contributes to the development of chiral superstructures and new materials and has a major impact on the discussion around the emergence of uniform chirality in biological systems. Herein we report chirality synchronization, leading to spontaneous chiral conglomerate formation in isotropic liquids of achiral and photoisomerizable azobenzene-based rod-like molecules. The position of fluorine substituents at the aromatic core is found to have a significant effect on the stability and the temperature range of these chiral liquids. Moreover, these liquid conglomerates occur in a new phase sequence adjacent to a 3D tetragonal mesophase.


Severe H1N1-infection during pregnancy.
H1N1 is known to induce fulminant courses in youths and young adults. We report the case of a 24-year gravida 4 para 2 with singleton pregnancy admitted to obstetrical unit for fever up to 38°C during the 20th week of a so far uncomplicated pregnancy. Ultrasound examination and urine test was inconspicuous. Throat complaints were initially relieved during antibiotic therapy, but the patient developed dyspnea with progressing signs of cyanosis. Intubation was necessary on the fifth day because of decreasing oxygen saturation. Coincidentally, progressive pancytopenia and increased inflammatory activity was recorded. Echocardiography, blood cultures, and bronchial lavage brought no pathological findings, but CT revealed acute respiratory distress syndrome and hepatomegaly. Recent human immunodeficiency virus, cytomegalic virus, herpes simplex virus, classical influenza and parainfluenza infections were excluded. An H1N1-infection was confirmed by PCR on the sixth day. The antiviral therapy was changed from zanamivir to oseltamivir. Extracorporeal membrane oxygenation was necessary due to insufficient oxygen saturation by mechanical ventilation. Until this time, pregnancy seemed to be unimpaired, but a sudden spontaneous expulsion of the fetus occurred on the seventh day (weight 460 g, no anomalies detectable). Curettage post abortem was not necessary. As a result of the antiviral therapy, H1N1-DNA was not detectable at day 16. Despite all endeavors, the respiratory situation could not be improved significantly; the patient additionally developed multiorgan failure during the time course and died on the 28th day of treatment. The recent case illustrates a very dangerous and imposing course of an H1N1-infection during pregnancy.


Nasopharingeal bacterial and fungal colonization in HIV-positive versus HIV-negative adults.
To compare mucosal flora in HIV-positive and HIV-negative subjects, to assess chemosusceptibility patterns of carriage isolates and to evaluate possible predisposing factors within the two groups. We analyzed microbes isolated from nasopharyngeal swabs in virologically suppressed and immunologically stable HIV-positive adult outpatients (n=105) at baseline and after 12 months and in an age-matched cohort of HIV-negative outpatients (n=100) at baseline. Bacteria and Candida spp strains were isolated and identified through standard biochemical assays and chemosusceptibility tests were performed. Multi Locus Sequence Typing was also determined to characterize Staphylococcus aureus isolates from HIV-infected persistent carriers. In HIV-positive patients a significantly higher rate of colonization by S. aureus as compared to HIV-negative controls was observed (19% vs 8%, p=0.02), with a relevant percentage of penicillin resistant strains (15% vs 0, p=0.24). Methicillin resistant strains were recovered only from HIV-positive subjects. Overall HIV-positive status was the only predictor of S. aureus colonization (OR 2.77, 95% CI 1.03;7.41, p=0.04). The nasopharyngeal bacterial flora differs between HIV-positive and HIV-negative subjects and appears relevant for possible development of staphylococcal infections in HIV-positive patients.


Theranostic nanoparticles.
Theranostic nanoparticles hold the potential to revolutionize disease management. Over the last decade, there has been growing interest in the engineering of various kinds of theranostic nanoparticles for simultaneous cancer imaging and therapy in small animals. Efficient targeting of theranostic nanoparticles to the tumor site is critical for both diagnosis and therapy. However, difficulties still exist in the engineering of biocompatible theranostic nanoparticles with highly specific in vivo tumor-targeting capabilities. Here, we discuss the current and prospective status of theranostic nanoparticles that actively target tumors, as well as the challenges that still exist.


Adenocarcinoma involving the urinary bladder.
A man in his 70s previously diagnosed with an adenocarcinoma of the prostate, received external beam radiation therapy (EBRT) and brachytherapy 11 years ago. Ten years later, he developed urinary symptoms and a cystoscopy identified a bladder neck tumour. A transurethral resection of a bladder tumour was performed, and pathology revealed a high-grade adenocarcinoma consistent with a colorectal primary. A colonoscopy was unremarkable, and imaging studies showed tumour involving the bladder and prostate. Tumour markers and a CARIS genomic prevalence score also favoured a colorectal cancer primary.The patient refused surgery and underwent chemoradiation with a combination of EBRT and brachytherapy with concurrent capecitabine. Imaging studies obtained 6 months after reirradiation revealed an enlarged left-sided mesorectal lymph node concerning for disease recurrence. The lymph node was treated with Stereotactic Body Radiation Therapy and his post-treatment imaging revealed a response to treatment with no other evidence of disease.


Buckwheat allergy: a potential problem in 21st century Britain.
Buckwheat is commonly consumed in many parts of the world and has recently become more available in the UK. Buckwheat allergy is well recognised in parts of mainland Europe and Asia, typically associated with consumption of specific regional foods. No adult cases of buckwheat allergy in the UK have been reported in the literature. The authors present two cases of buckwheat allergy that presented to our UK allergy service recently. A 57-year-old man presented with anaphylaxis after eating home-baked bread prepared using buckwheat flour bought in France. In the second case, a 63-year-old lady presented with bronchospasm and urticaria after consuming health-food muesli. Sensitisation was confirmed in both cases by positive skin prick testing and specific IgE to buckwheat. Given the growing popularity of foods that may contain buckwheat, including ethnic and health-food ranges, buckwheat allergy is likely to become increasingly common in the UK.


Myocardial imaging with technetium-99m-tetrofosmin: comparison of one-day and two-day protocols.
There is no evidence of myocardial redistribution after tetrofosmin injection, therefore, two separate injections are needed to differentiate scar from ischemia with this tracer. The injections can be given on the same day (one-day protocol) or on separate days (two-day protocol). As part of a Phase II clinical study, a one-day protocol was compared with a two-day protocol. Fifty-five patients with suspected coronary artery disease were studied according to the following protocol: on the first day at rest, anterior, left lateral, left anterior oblique 40 degrees and 70 degrees images were acquired 30 min after injection of 8 mCi of tetrofosmin for 5 min each. Two days later, exercise and rest images were acquired on the same day. At peak exercise, 8 mCi of tetrofosmin were injected and 30 min later the same four standard planar images were recorded as on Day one. Four hours after the exercise injection, 24 mCi of tetrofosmin were injected at rest and imaging was repeated 30 min later. Qualitative comparisons between the one- and two-day protocols were performed in 50 patients in whom all data were available following blinded evaluation of images by three readers. All three readers reported identical results for the 26 patients. A difference in extent or location between the observers was found in seven patients, differences between normal and abnormal in eight patients, while discrepancies between ischemia and necrosis were noted in four patients. In five patients, an ischemic area was found according to the one-day protocol, but according to the data of the two-day protocol, this area was judged to be necrotic. One observer reported the opposite in one patient. These discrepancies between the reversibility of defects were restricted to the inferior wall. Comparison with 201Tl data showed no systematic pattern of variation. Tetrofosmin can be used in a one-day protocol. However, in planar imaging, the inferior wall should be reported with caution.


Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis.
Pathogenic bacteria have evolved highly specialized systems to extract essential nutrients from their hosts. Mycobacterium tuberculosis (Mtb) scavenges lipids (cholesterol and fatty acids) to maintain infections in mammals but mechanisms and proteins responsible for the import of fatty acids in Mtb were previously unknown. Here, we identify and determine that the previously uncharacterized protein Rv3723/LucA, functions to integrate cholesterol and fatty acid uptake in Mtb. Rv3723/LucA interacts with subunits of the Mce1 and Mce4 complexes to coordinate the activities of these nutrient transporters by maintaining their stability. We also demonstrate that Mce1 functions as a fatty acid transporter in Mtb and determine that facilitating cholesterol and fatty acid import via Rv3723/LucA is required for full bacterial virulence in vivo. These data establish that fatty acid and cholesterol assimilation are inexorably linked in Mtb and reveals a key function for Rv3723/LucA in in coordinating thetransport of both these substrates.


Deformability considerations in filtration of biological cells.
Biological cells are highly sensitive to variation in local pressure because cellular membranes are not rigid. Unlike microbeads, cells deform under pressure or even lyse. In isolating or enriching cells by mechanical filtration, pressure-induced lysis is exacerbated when high local fluidic velocity is present or when a filter reaches its intended capacity. Microfabrication offers new possibilities to design fluidic environments to reduce cellular stress during the filtration process. We describe the underlying biophysics of cellular stress and general solutions to scale up filtration processes for biological cells.


Mechanisms involved in the loss of antibody-mediated adherence of macrophages to lung-stage schistosomula of Schistosoma mansoni in vitro.
Sera from rabbits vaccinated with irradiated cercariae mediated cell (P388D1 or mouse peritoneal macrophage) adherence to lung-stage schistosomula (LS) but such antibody-mediated cell adherence was short-lived in contrast to cell adherence to mechanically transformed schistosomula (MS). Thus LS lost 50% of their adherent cells within 3-6 h in culture and up to 90% by 24 h, whereas adherence to MS was undiminished during this time. Rapid loss of adherent cells was unique to schistosomula that had developed to the lung stage because schistosomula recovered from the skin up to 3 days post-infection did not exhibit the rapid cell loss shown by 3-day LS. To determine whether cell loss was caused by loss of surface antigenicity during culture LS were cultured on their own for up to 24 h and at various intervals samples of schistosomula were tested for antigenicity by addition of immune serum and cells. Levels of adherence to both MS and LS were maintained throughout the incubation period. When antibody-opsonized schistosomula were washed and indicator cells added at progressive intervals, persistence of adherence was again demonstrated, showing that antibody binding to LS had not promoted surface antigen loss or degradation of bound antibody. It was then shown, by adding fresh macrophages to cultures up to 24 h old that LS which had lost their adherent cells nevertheless retained bound antibody, and comparison of adherence of 'used' and 'fresh' cells to MS and LS showed that the cytoadherence properties of macrophages were not significantly reduced during their culture with LS from which cells had been lost.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation of Promoter Methylation of RASSF1A and ATM in Peripheral Blood of Breast Cancer Patients and Healthy Control Individuals.
Breast cancer (BC) is the most common cancer among women and has high mortality rates. Early detection is supposed to be critical for the patient's prognosis. In recent years, several studies have investigated global DNA methylation profiles and gene-specific DNA methylation in blood-based DNA to develop putative screening markers for cancer. However, most of the studies have not yet been validated. In our study, we analyzed the promoter methylation of RASSF1A and ATM in peripheral blood DNA of 229 sporadic patients and 151 healthy controls by the MassARRAY EpiTYPER assay. There were no significant differences in DNA methylation levels of RASSF1A and ATM between the sporadic BC cases and the healthy controls. Furthermore, we performed the Infinium HumanMethylation450 BeadChip (450K) array analysis using 48 sporadic BC cases and 48 healthy controls (cases and controls are the same from those of the MassARRAY EpiTYPER assay) and made a comparison with the published data. No significant differences were presented in DNA methylation levels of RASSF1A and ATM between the sporadic BC cases and the healthy controls. So far, the evidence for powerful blood-based methylation markers is still limited and the identified markers need to be further validated.


Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary absorption of encapsulated insulin compared with co-administered insulin.
We have previously shown that aerosolized liposomes with dipalmitoyl phosphatidylcholine (DPPC) enhance the pulmonary absorption of encapsulated insulin. In this study, we aimed to compare insulin encapsulated into the liposomes versus co-administration of empty liposomes and unencapsulated free insulin, where the DPCC liposomes would serve as absorption enhancer. The present study provides the useful information for development of noninvasive treatment of diabetes. Co-administration of empty DPPC liposomes and unencapsulated free insulin was investigated in vivo to assess the potential enhancement in protein pulmonary absorption. Co-administration was compared to DPPC liposomes encapsulating insulin, and free insulin. DPPC liposomes enhanced the pulmonary absorption of unencapsulated free insulin; however, the enhancing effect was lower than that of the DPPC liposomes encapsulating insulin. The mechanism of the pulmonary absorption of unencapsulated free insulin by DPPC liposomes involved the opening of epithelial cell space in alveolar mucosa, and not mucosal cell damage, similar to that of the DPPC liposomes encapsulating insulin. In an in vitro stability test, insulin in the alveolar mucus layer that covers epithelial cells was stable. These findings suggest that, although unencapsulated free insulin spreads throughout the alveolar mucus layer, the concentration of insulin released near the absorption surface is increased by the encapsulation of insulin into DPPC liposomes and the absorption efficiency is also increased. We revealed that the encapsulation of insulin into DPPC liposomes is more effective for pulmonary insulin absorption than co-administration of DPPC liposomes and unencapsulated free insulin.


Effectiveness of a 2-year menopause medicine curriculum for obstetrics and gynecology residents.
Previous work has shown American obstetrics and gynecology (OB/GYN) residents are lacking in menopause training. Our objective was to assess the effectiveness of a 2-year menopause medicine curriculum in improving OB/GYN residents' knowledge and self-assessed competency in menopause topics. We developed a menopause medicine-teaching curriculum for OB/GYN residents at our academic hospital-based residency program. The 2-year curriculum was composed of year 1: four 1-hour lectures and one 2-hour lab with cases presentations, and year 2: three 1-hour lectures and one 2-hour lab. Core topics included menopause physiology, hormone therapy, breast health, bone health, cardiovascular disease, and autoimmune disease. Pre- and posttests assessed resident knowledge and comfort in core topics, and a pre- and postcurriculum survey assessed utility and learning satisfaction. From July 2011 to June 2013, 34 OB/GYN residents completed the menopause curriculum annually with an average attendance at each module of 23 residents. Pre-/posttest scores improved from a mean pretest score of 57.3% to a mean posttest score of 78.7% (P < 0.05). Before the curriculum, most residents did not feel comfortable managing menopause patients with 75.8% reporting feeling "barely comfortable" and 8.4% feeling "not at all comfortable." After the 2-year curriculum, 85.7% reported feeling "comfortable/very comfortable" taking care of menopause patients. The majority of residents (95.2%) reported the menopause curriculum was "extremely useful." A 2-year menopause medicine curriculum for OB/GYN residents utilizing lectures and a lab with case studies is an effective modality to improve resident knowledge required to manage menopause patients.


The peroxisome proliferator-activated receptor β/δ (PPARβ/δ) agonist GW501516 prevents TNF-α-induced NF-κB activation in human HaCaT cells by reducing p65 acetylation through AMPK and SIRT1.
Nuclear factor (NF)-κB is a ubiquitously expressed transcription factor controlling the expression of numerous genes involved in inflammation. The aim of this study was to evaluate whether activation of the peroxisome proliferator-activated receptor (PPAR) β/δ prevented TNF-α-induced NF-κB activation in human HaCaT keratinocytes and, if so, to determine the mechanism involved. The PPARβ/δ agonist GW501516 inhibited the increase caused by TNF-α in the mRNA levels of the NF-κB target genes interleukin 8 (IL-8), TNF-α and thymic stromal lymphopoietin (TSLP). Likewise, GW501516 prevented the increase in NF-κB DNA-binding activity observed in cells exposed to TNF-α. The reduction in NF-κB activity following GW501516 treatment in cells stimulated with TNF-α did not involve either increased IκBα protein levels or a reduction in the translocation of the p65 subunit of NF-κB. In contrast, GW501516 treatment decreased TNF-α-induced p65 acetylation. Acetylation of p65 is mainly regulated by p300, a transcriptional co-activator that binds to and acetylates p65. Of note, AMP kinase (AMPK) activation phosphorylates p300 and reduces its binding to p65. GW501516 increased AMPK phosphorylation and the subsequent p300 phosphorylation, leading to a marked reduction in the association between p65 and this transcriptional co-activator. In addition, treatment with the PPARβ/δ agonist increased SIRT1 protein levels. Finally, the reduction in IL-8 mRNA levels following GW501516 treatment in TNF-α-stimulated cells was abolished in the presence of the PPARβ/δ antagonist GSK0660, the AMPK inhibitor compound C and the SIRT1 inhibitor sirtinol, indicating that the effects of GW501516 on NF-κB activity were dependent on PPARβ/δ, AMPK and SIRT1, respectively.


Ontogenesis of enzyme systems deaminating different monoamines.
1 A detailed investigation into the postnatal development of the activity of the enzyme monoamine oxidase (MAO) in the rat and domestic pig was carried out. 2 MAO activity was measured in littermate male rats aged between 3 and 122 days belonging to six breeding colonies. The tissues studied were three brain regions in which monoamines may play a role in neuronal transmission (septum, hypothalamus, corpus striatum) and, for comparison, in the cerebellum. Liver, heart and adrenal glands were the peripheral organs studied. The following substrates were used to measure MAO activity in each tissue homogenate: kynuramine, tyramine, dopamine, tryptamine and 5-hydroxytryptamine (5-HT). 3 MAO activity towards kynuramine, tyramine and dopamine increased after birth in all brain regions and also in the liver, to reach maximal values between days 40 and 80. In the heart and the adrenal glands enzyme activity remained low up to 30-40 days and then increased steeply. This was the case in all litters examined. 4 All tissues deaminated more tyramine than dopamine. In the liver, the ratio of the quantities of tyramine deaminated/dopamine deaminated was approx. 2 at all ages. In the homogenates of whole brains (including or excluding the hypothalamus and striatum) this ratio was also 2 at all ages. In contrast in the isolated striatum and hypothalamus it was first much higher and reached a value of 2 only at an age of about 20 days. This may indicate an independent development of a dopamine and a tyramine deaminating enzyme system in discrete brain regions. It was suggested, that the low ability to deaminate dopamine in discrete brain regions may be due to the local presence of an enzyme inhibitor which becomes too diluted to be active in homogenates of whole brain. 5 Deamination of tryptamine in the striatum decreased between day 5 and 20 in 3 out of 4 colonies tested. There was a large fall in the deamination of 5-HT in all tissues of one group of rats, but in another 4 groups the tissues of the 5 day old rats deaminated smaller amounts of 5-HT than those of the older rats. 6 Purified hypothalamic mitochondria from 40 day old rats deaminated more tyramine and dopamine but not tryptamine per mg protein than those from 5 day old rats. 7 In the domestic pig there was a significant rise in the values in hippocampal MAO activity towards dopamine and tyramine from the foetus (55 day gestation) to the 1 week old piglet. A further steady rise up to week 6 was indicated, but this rise was not statistically significant. The difference between rat and pig probably reflected the much higher degree of maturity of the latter at birth. 8 In the hippocampus of the pig the ratio between the amount of tyramine deaminated/dopamine deaminated decreased from greater than 10 (foetus) to 4.8 in the 6 week old pig and 2 in the adult.


The Impact of Anti-Tumor Necrosis Factor Alpha Therapy on Postoperative Complications in Pediatric Crohn's Disease.
The incidence of Crohn's disease (CD) within the pediatric population is increasing worldwide. Despite a growing number of these patients receiving anti-tumor necrosis factor α therapy (anti-TNF-α), one-third of them still require surgery. There is limited data as to whether anti-TNF-α influences postoperative complications. We evaluated postoperative complications in patients who were or were not exposed to anti-TNF-α therapy in our institutional cohort. A retrospective review of CD patients who underwent abdominal surgery between September 2013 and September 2018 was performed. The patients were divided into two groups based on whether they were treated with anti-TNF-α within 90 days before surgery. Thirty-day postoperative complications were assessed using Clavien-Dindo classification (D-C); this examination included surgical site infections (SSIs), stoma complications, intra-abdominal septic complications, non-SSIs, bleeding, ileus, readmission rate, and return to the operating room. Mann-Whitney U-test, Fisher's exact test, and multivariate logistic regression analyses were used for statistical analysis. Sixty-five patients (41 males) with a median age of 16 years (range: 7-19) at the time of operation were identified. The most common surgery was ileocecal resection in 49 (75%) patients. Forty-three (66.2%) patients were treated with anti-TNF-α preoperatively. Seven patients (11%) experienced postoperative complications. There was no statistically significant difference in postoperative complication in patients who did or did not receive anti-TNF-α before surgery (D-C minor 2.3% vs. 4.6%, p = 1; D-C major 7% vs. 9.1%, p = 1). The use of anti-TNF-α in pediatric CD patients within the 90 days prior to their abdominal surgery was not associated with an increased risk of 30-day postoperative complications.


Autoregressive linear least square single scanning electron microscope image signal-to-noise ratio estimation.
A technique based on linear Least Squares Regression (LSR) model is applied to estimate signal-to-noise ratio (SNR) of scanning electron microscope (SEM) images. In order to test the accuracy of this technique on SNR estimation, a number of SEM images are initially corrupted with white noise. The autocorrelation function (ACF) of the original and the corrupted SEM images are formed to serve as the reference point to estimate the SNR value of the corrupted image. The LSR technique is then compared with the previous three existing techniques known as nearest neighbourhood, first-order interpolation, and the combination of both nearest neighborhood and first-order interpolation. The actual and the estimated SNR values of all these techniques are then calculated for comparison purpose. It is shown that the LSR technique is able to attain the highest accuracy compared to the other three existing techniques as the absolute difference between the actual and the estimated SNR value is relatively small. SCANNING 38:771-782, 2016. © 2016 Wiley Periodicals, Inc.


Coronoid fractures of the elbow.
Coronoid fractures of the ulna are relatively uncommon, yet critical injuries to recognize. They often occur in association with elbow dislocations and play an important role in elbow instability. Historic recommendations are to fix all large coronoid fracture fragments, as well as small fracture fragments associated with instability. There is little data regarding management of small coronoid fracture fragments. The coronoid process acts as a bony buttress to prevent posterior dislocation and has three soft tissue insertions which lend stability as well: the anterior joint capsule of the elbow, the brachialis muscle and the medial ulnar collateral ligament. Injured patients often present with swelling, tenderness and limited range of motion. After obtaining a detailed history and performing a careful physical examination, plain radiographs should be obtained. If present, dislocations are reduced and post-reduction stability is assessed. If the elbow is unstable, management usually consists of a combination of bony and soft-tissue repairs often including coronoid process repair. Loss of motion is the most common complication of these injuries. The current recommendation is to repair virtually all coronoid fractures associated with instability.


Contrast-enhanced ultrasound-guided percutaneous microwave ablation of renal cell carcinoma that is inconspicuous on conventional ultrasound.
This study was designed to determine the safety, effectiveness and feasibility of contrast-enhanced ultrasound (CEUS)-guided percutaneous microwave ablation (MWA) of renal cell carcinoma (RCC) that is inconspicuous on conventional ultrasound (US). A total of 32 RCC nodules in 29 patients (23 men and 6 women) were treated with CEUS-guided percutaneous MWA between January 2010 and September 2014. The median maximum diameter of the nodules was 2.4 cm (interquartile range: 1.8-2.9 cm). The US contrast agent was SonoVue, a second-generation contrast agent. CEUS was applied before the needle was inserted into the tumour, and percutaneous MWA was performed under CEUS-guidance. In total 31 tumours were successfully visualised via CEUS using 1-2 (1.0-2.0 mL) contrast agent injections, and percutaneous MWA was performed under CEUS-guidance. The technical success rate of CEUS-guided percutaneous MWA of RCC was 96.9% (31/32). The mean number of sessions of CEUS-guided percutaneous MWA for each tumour was 1.2 ± 0.4. The mean duration of energy application for each tumour was 7.3 ± 2.7 min. All patients were followed up for 3-71 months (median 17 months) to observe the therapeutic effects and complications. The therapeutic effects were assessed at follow-up with computed tomography (CT) or magnetic resonance imaging (MRI) and CEUS. There was no local tumour progression and the technique effectiveness rate was 100% (31/31). The complications rate was 6.5% and the major complications rate was 3.2%. We observed one case of pleural effusion and one case of renal subcapsular haemorrhage after the percutaneous MWA procedures. CEUS-guided percutaneous MWA is a safe, efficient and feasible therapy for patients with RCCs inconspicuous on conventional US.


Determination of cut-off positivity values in nasal challenge testing of patients with allergic rhinitis.
Nasal challenge testing with allergen extracts is currently used to diagnose nasal allergy and, to a greater extent, in studies of pathophysiology of allergic rhinitis. The resulting nasal obstruction, measured as nasal airway resistance (NAR), is determined by rhinomanometry (RMM). The aim of this study was to define a cut-off NAR value for a positive response in a nasal allergen challenge test. Forty-two, grass-allergic adult patients and 40 nonallergic adults were challenged out of the grass pollen season under standard conditions with timothy grass extract administered intranasally in doses increasing from 10 to 1500 IU/mL. Inspiratory NAR was determined by computerized anterior active RMM. The cut-off value for a positive test was determined from receiver operating characteristic curves plotted from these data with the LABROC1 computer program. In addition, the subjects' nasal cycle was recorded during the four hours preceding the allergen challenge. The patients' mean NAR value at baseline (0.33 Pa/cc/sec) and when challenged with normal saline solution did not differ from those of the control subjects. The patients, but not the control subjects, experienced typical nasal allergic symptoms when challenged with the grass extract. The control subjects had no symptoms and their NAR did not change significantly when they were challenged with the same extract. All 42 allergic patients had measurable increases in NAR at the 800 IU/mL allergen dose; 19/42 patients had complete obstruction (i.e., NAR unmeasurable) when challenged with the 1500 IU/mL dose. The maximum diagnostic value (= sensitivity + specificity at the discriminator position on the receiver operating characteristic curves) was 1.96 with the 800 IU/mL dose. At that dose, the NAR cut-off value was 0.91 Pa/cc/sec, which was 2.7 times greater than their mean value at baseline. NAR varied less than 1-fold between the maximum and minimum points of the normal nasal cycle in both groups of subjects. An increase of NAR of nearly three-fold during nasal allergen challenge compared to the baseline value determined by computerized anterior active RMM discriminates best patients with allergic rhinitis from nonallergic adults.


[Poverty and sociocultural factors in the use of maternal health services in Ivory Coast].
Better health for populations is linked to the adequate access to health services. This is particularly important in developing countries, where a number of economic, social, and geographic barriers exist. Pregnant women are particularly at risk, as they have many health needs and problems. In addition, the use of maternal health services is particularly influenced by economic and socio-cultural factors. Therefore, we intended to appreciate the association between poverty, socio-cultural factors and use of maternal health services in Ivory Coast. For this study, our data were from the demographic and health survey in Ivory Coast in 1998. We used the logistic regression models to analyze the relation between poverty, socio-cultural factors and use of services (antenatal care, type of delivery). 62.4% of women used antenatal care adequately and 48.9% delivered in good conditions. Poverty is strongly linked to the use of services whatever the socio-cultural and demographic aspects are, with the poor using less services than the richer. Concerning the impact of socio-cultural characteristics, women living alone or with one adult (OR=1.60; 95% IC=1.06-2.42), those who are Christian (OR=1.83; 95% IC=1.25-2.67) or Akan are more likely to have adequate antenatal care than women living with 5 adults or more, having traditional or no religion, and those who are Senoufo or non Ivorian. Besides, when the number of children increases, they are less likely to consult. Primiparous, Christians (OR=2.45; 95% IC=1.68-3.59) or Muslims (OR=1.73; 95% IC=1.10-2.72) are more likely to deliver in a health center with a qualified assistance. Poverty has a negative effect on the use of maternal services but one should also take into account certain socio-cultural characteristics, namely number of adults in the household, parity, ethnicity and religion. While reducing poverty, it appears important to involve family members and religious or ethnic leaders in order to improve this use.


Inhibiting neddylation modification alters mitochondrial morphology and reprograms energy metabolism in cancer cells.
Abnormal activation of neddylation modification and dysregulated energy metabolism are frequently seen in many types of cancer cells. Whether and how neddylation modification affects cellular metabolism remains largely unknown. Here, we showed that MLN4924, a small-molecule inhibitor of neddylation modification, induces mitochondrial fission-to-fusion conversion in breast cancer cells via inhibiting ubiquitylation and degradation of fusion-promoting protein mitofusin 1 (MFN1) by SCFβ-TrCP E3 ligase and blocking the mitochondrial translocation of fusion-inhibiting protein DRP1. Importantly, MLN4924-induced mitochondrial fusion is independent of cell cycle progression, but confers cellular survival. Mass-spectrometry-based metabolic profiling and mitochondrial functional assays reveal that MLN4924 inhibits the TCA cycle but promotes mitochondrial OXPHOS. MLN4924 also increases glycolysis by activating PKM2 via promoting its tetramerization. Biologically, MLN4924 coupled with the OXPHOS inhibitor metformin, or the glycolysis inhibitor shikonin, significantly inhibits cancer cell growth both in vitro and in vivo. Together, our study links neddylation modification and energy metabolism, and provides sound strategies for effective combined cancer therapies.


Adherence to guidelines for antiulcer drug prescription in patients receiving low-dose aspirin therapy in Japan.
Prevalence of guideline adherence for antiulcer drug prescription in patients receiving low-dose aspirin (LDA) therapy was examined and the association of risk factors with the adherence was assessed. A retrospective cohort study using a population-based longitudinal healthcare database was conducted. Claims data between January 2005 and April 2016 were analyzed. A total of 3,079 patients were included in the study. The selected patients taking LDA were divided into two categories: those taking and those not taking antiulcer drugs in an inpatient setting. Additionally, they were classified into four groups according to the time antiulcer therapy was initiated. The risk factors for ulcer, such as history of gastrointestinal injuries; age ≥ 65 years; and concomitant use of anticoagulants, antiplatelets, oral corticosteroids, and nonsteroidal anti-inflammatory drugs except aspirin, were assessed. A total of 3,079 patients were included in the study. The rate of LDA patients using antiulcer drugs was 65.2%, with the strongest single factor associated with the use of antiulcer drugs being the concomitant use of corticosteroids. Among the LDA patients not taking antiulcer drugs, 66.8% had more than one risk factor. Irrespective of the use of concomitant treatment with antiulcer drug prior to hospital admission, 78.3% of the LDA patients continued their home regimen after hospital admission. Our results showed that the requirement of antiulcer therapy is not routinely evaluated at hospital admission, and antiulcer drugs for patients with ulcer risks are under-prescribed. Developing strategies to screen gastrointestinal risk factors at hospital admission is required to improve the guideline adherence for LDA-induced ulcer.


[Expression of S100A2 in secondarily radioresistant pancreatic cancer cells and significance thereof].
To investigate the association of S100A2 expression with the secondary radioresistance in pancreatic cancer cells. Human pancreatic cancer cells of the line SW1990, parental line, and the secondarily radioresistant human pancreatic cancer cells of the line SW1990/R were cultured and inoculated into the wells of a 6-well plate. 5-Aza-2'-deoxycytidine (5-aza-DC) of different concentrations was added into the culture fluid. Forty-eight hours later X-ray irradiation was conducted. Cloning efficiency assay was used to assess the cell survival. The cell cycle was analyzed by flow cytometry. The mRNA expression of S100A2 was examined by real-time RT-PCR and the protein expression of S100A2 was examined by immunofluorescence quantitative analysis. The S100A2 mRNA expression level of the SW1990 line was significantly higher than that of the SW1990/R line. Treated by 5-aza-dC, the S100A2 mRNA expression level of the SW1990/R line increased by 2 approximately 3 times. The S100A2 protein expression level of the SW1990 line was significantly higher than that of the SW1990/R line (t = 3.648, P = 0.022). Treated by 5-aza-dC, the S100A2 protein expression level of the SW1990/R line increased, by 5 times at most (t = -11.404, P = 0.001). The G(2)/M of the SW1990 line was 16.2%, significantly higher than that of the SW1990/R line (16.2%), and the G(2)/M levels of the SW1990/R line treated by 5-aza-dC of different concentrations were all increased dose-dependently. The colony-forming rates of the SW1990/R line of the 5-aza-dC + irradiation groups were all significantly lower than that of the SW1990/R line of the pure irradiation group, even the dose of 5-aza-dC was as low as 0.025 microm. The SF2 (cell survival rate with the irradiation dose of 2 Gy) of the 5-aza-dC + irradiation group was 0.122, significantly lower than that of the pure irradiation group (0.460). The expression level of S100A2 is low in the radioresistant pancreatic cancer cells, which may be one of the mechanisms of radioresistance of these cells.


Catheter simulator software tool to generate electrograms of any multi-polar diagnostic catheter from 3D atrial tissue.
Simulations are excellent tools for assessing new therapeutic strategies and are often conducted before implementing new therapy options in a clinical practice. For patients suffering from a heart arrhythmia, the main source of information comes from an intracardiac catheter. One of the common catheters is a Lasso multi-pole diagnostic catheter, which is a catheter that has 20 electrodes in a circular pattern. In this paper, we developed algorithm and simulation software that allows the users to place a multi-pole catheter on the atrial endocardial surface and record electrograms. In 3D atrial tissue, the plane of principal curvature is determined using eigenvectors of catheter vertices, from where the normals are projected and registered to the surface using 3D geodesic distance. This tool provides a platform for performing customized virtual cardiac experiments.


Influence of Alcohol Consumption on the Risk of Systemic Lupus Erythematosus Among Women in the Nurses' Health Study Cohorts.
Moderate alcohol consumption has antiinflammatory properties and is associated with reduced cardiovascular disease and rheumatoid arthritis risks. We investigated the association between alcohol consumption and systemic lupus erythematosus (SLE) risk among women followed in the Nurses' Health Study (NHS) cohorts. We conducted a prospective cohort analysis among 204,055 women in NHS (1980-2012) and NHSII (1989-2011) who were free of connective tissue disease and provided alcohol information at baseline. Alcohol consumption was assessed using a semiquantitative food frequency questionnaire every 2-4 years. We validated incident SLE through medical record review after self-report. Cox proportional hazards models estimated hazard ratios (HRs) for SLE based on cumulative average alcohol intake, adjusting for potential confounders. Results were meta-analyzed using DerSimonian and Laird random-effects models. We further investigated SLE risk associated with wine, beer, and liquor intake. We identified 125 incident SLE cases in NHS and 119 in NHSII. Mean ± SD age at SLE diagnosis was 55.8 ± 9.5 years in NHS and 43.4 ± 7.7 years in NHSII. Compared to no alcohol intake, the meta-analyzed multivariable HR for cumulative alcohol consumption ≥5 gm/day was 0.61 (95% confidence interval [95% CI] 0.41-0.89). When limiting alcohol exposure to >4 years prior to SLE diagnosis, the multivariable HR was similar: 0.61 (95% CI 0.41-0.91). Women who drank ≥2 servings/week of wine had significantly decreased SLE risk (HR 0.65, 95% CI 0.45-0.96) compared to women who did not drink wine. In these large prospective cohorts, we demonstrated an inverse association between moderate alcohol consumption (≥5 grams or 0.5 drink/day) and SLE risk in women.


Ovalbumin-specific IgE/IgG4 ratio might improve the prediction of cooked and uncooked egg tolerance development in egg-allergic children.
Accurate predictors of natural tolerance development to cooked and uncooked egg are needed in egg-allergic patients. To compare the diagnostic performance of different immunological tests in relation to egg allergy versus tolerance. Children aged 5-18 years diagnosed with IgE-mediated egg allergy were prospectively recruited. All followed an egg-free diet. Prick test and specific IgE (sIgE) to ovalbumin, ovomucoid and egg white, ovalbumin-sIgG4 and ovomucoid-sIgG4 were determined. By boiled and raw egg challenges, children were classified as cooked egg allergic (CEA, n = 50) or tolerant (CET, n = 35), and uncooked egg allergic (UEA, n = 64) or tolerant (UET, n = 21). Statistics. Comparative analysis (CEA vs. CET and UEA vs. UET). Multivariate logistic regression. Partial receiver operating characteristic curve analysis of tests in relation to CEA and UEA. Negative decision points were defined as cut-offs with sensitivity 95%. Ovalbumin-sIgG4 resulted an independent protective factor for uncooked egg allergy. To identify patients with high probability of egg tolerance, ovalbumin-sIgE/sIgG4 tended to perform better than sIgE and prick, specifically in children with ovalbumin-sIgE < 1.9 kU/L (for UEA) and ovomucoid-sIgE < 2.12 kU/L (for CEA). The most accurate cut-offs to recommend challenges were ovalbumin-sIgE/sIgG4 below 2.49 for cooked egg and 1.45 for uncooked egg, which associated 89.5% and 80% probability of tolerance (negative likelihood ratios 0.08 and 0.06), respectively. These cut-offs identified correctly as tolerant an additional 23% and 14% of children with negative challenges to cooked and uncooked egg, respectively, in comparison with sIgE negative decision points. Additionally, prick test tended to perform better than sIgE alone in predicting cooked and uncooked egg tolerance for ovomucoid-sIgE < 0.92 kU/L and ovalbumin-sIgE < 1.37 kU/L, respectively. Ovalbumin-specific IgG4 is an independent predictor of tolerance development to uncooked egg. Ovalbumin-sIgE/sIgG4 ratio, followed by skin prick test (SPT), seems to perform better than sIgE in identifying egg-allergic children with high probability of tolerance to cooked and uncooked egg over follow-up.


Shiga toxin-producing Escherichia coli in swine: the public health perspective.
Shiga toxin-producing Escherichia coli (STEC) strains are food-borne pathogens that are an important public health concern. STEC infection is associated with severe clinical diseases in human beings, including hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS), which can lead to kidney failure and death. Cattle are the most important STEC reservoir. However, a number of STEC outbreaks and HUS cases have been attributed to pork products. In swine, STEC strains are known to be associated with edema disease. Nevertheless, the relationship between STEC of swine origin and human illness has yet to be determined. This review critically summarizes epidemiologic and biological studies of swine STEC. Several epidemiologic studies conducted in multiple regions of the world have demonstrated that domestic swine can carry and shed STEC. Moreover, animal studies have demonstrated that swine are susceptible to STEC O157:H7 infection and can shed the bacterium for 2 months. A limited number of molecular epidemiologic studies, however, have provided conflicting evidence regarding the relationship between swine STEC and human illness. The role that swine play in STEC transmission to people and the contribution to human disease frequency requires further evaluation.


Influence of speed variation and age on ground reaction forces and stride parameters of children's normal gait.
The aim of this study was to assess the influence of both age and speed on ground reaction forces and temporal parameters during normal gait in children. Fifteen children aged 4-6 years (group 1), 16 aged 6-8 years (group 2), and 16 aged 8-10 years (group 3) walked at 2.7 km/h, 3.6 km/h, and 4.5 km/h on a treadmill. For each child thirty successive steps were recorded. The influence of speed and age on normalized gait parameters was examined with two-way analysis of variance. The first vertical peak force (Fz1) and all the antero-posterior forces of group 1 were higher than those of the other groups for the three speeds. The minimum vertical force (Fz2), the second vertical peak force (Fz3), and the duration of stride and stance were significantly higher in groups 2 and 3. For all the groups, Fz1 and all the antero-posterior forces increased with the speed while Fz2, stride, stance, and double-stance duration decreased. Fz3 was not influenced by speed variation. The results of this study show that age and walking speed influence ground reaction forces and stride time parameters in 4- to 10-year-old children.


Categorical data analysis in public health.
A greater variety of categorical data methods are used today than 15 years ago. This article surveys categorical data methods widely applied in public health research. Whereas large sample chi-square methods, logistic regression analysis, and weighted least squares modeling of repeated measures once comprised the primary analytic tools for categorical data problems, today's methodology is comprised of a much broader range of tools made available by increasing computational efficiency. These include computational algorithms for exact inference of small samples and sparsely distributed data, conditional logistic regression for modeling highly stratified data, and generalized estimating equations for cluster samples. The latter, in particular, has found wide use in modeling the marginal probabilities of correlated counted, binary, and multinomial outcomes. The various methods are illustrated with examples including a study of the prevalence of cerebral palsy in very low birthweight infants and a study of cancer screening in primary care settings.


Allelopathic exudates of cogongrass (Imperata cylindrica): implications for the performance of native pine savanna plant species in the southeastern US.
We conducted a greenhouse study to assess the effects of cogongrass (Imperata cylindrica) rhizochemicals on a suite of plants native to southeastern US pine savanna ecosystems. Our results indicated a possible allelopathic effect, although it varied by species. A ruderal grass (Andropogon arctatus) and ericaceous shrub (Lyonia ferruginea) were unaffected by irrigation with cogongrass soil "leachate" (relative to leachate from mixed native species), while a mid-successional grass (Aristida stricta Michx. var. beyrichiana) and tree (Pinus elliottii) were negatively affected. For A. stricta, we observed a 35.7 % reduction in aboveground biomass, a 21.9 % reduction in total root length, a 24.6 % reduction in specific root length and a 23.5 % reduction in total mycorrhizal root length, relative to the native leachate treatment. For P. elliottii, there was a 19.5 % reduction in percent mycorrhizal colonization and a 20.1 % reduction in total mycorrhizal root length. Comparisons with a DI water control in year two support the possibility that the treatment effects were due to the negative effects of cogongrass leachate, rather than a facilitative effect from the mixed natives. Chemical analyses identified 12 putative allelopathic compounds (mostly phenolics) in cogongrass leachate. The concentrations of most compounds were significantly lower, if they were present at all, in the native leachate. One compound was an alkaloid with a speculated structure of hexadecahydro-1-azachrysen-8-yl ester (C23H33NO4). This compound was not found in the native leachate. We hypothesize that the observed treatment effects may be attributable, at least partially, to these qualitative and quantitative differences in leachate chemistry.


[Chemical modification of recombinant adenovirus-associated virus vectors].
Recombinant adenovirus-associated virus (rAAV) vectors mediated gene delivery system has been widely used in the treatments of cancer or other genetic diseases. It is considered to be one of the most promising vector owing to its non-pathogenicicity, low immune response, potential to integrate site-specif-ically, persistent and stable gene expression. However, it was limited in clinical applications because it is easy to be neutralized in serum and non-selection to the target site. Chemical modifications of rAAV have been studied to overcome those problems. This article reviewed the progress of chemical modifications of rAAV by various compounds and different modification methods, and predicted what the researches needed to do in the future.


Age-dependent hypothalamic expression of neuropeptides in wild-type and melanocortin-4 receptor-deficient mice.
In young (35- to 56-day-old) and middle-aged (9-mo-old) wild-type (+/+) and melanocortin-4 receptor (MC4R)-deficient (+/-, -/-) mice, expressions of neuropeptide Y (NPY), agouti-related protein (AGRP), pro-opiomelanocortin (POMC), and cocaine-and-amphetamine-regulated transcript (CART) were analyzed in the arcuate nucleus (ARC) and adjacent regions comprising the dorsomedial (DMN) and ventromedial (VMN) nucleus. In the ARC of young mice, NPY and AGRP expression increased and POMC and CART expression decreased with body fat content. Adjusting for the influence of body fat content by ANCOVA showed that the levels of NPY, POMC, and CART were highest and of AGRP lowest in young -/- mice. In the middle-aged mice, feedback from body fat content was weakened. For -/- mice ANCOVA revealed higher NPY and AGRP, lower POMC, and unchanged CART expression levels relative to young -/- mice. In the DMN and VMN, POMC and AGRP signals were absent at each age. CART was expressed in the DMN independent of age, fat content, and genotype. For NPY expression, an age-dependent induction was found in the DMN and VMN; it was absent in the young but present in the middle-aged mice, showing close positive correlations between body fat content and the numbers of NPY-labeled cells which were further enhanced in -/- mice. Thus MC4R deficiency augments age-induced NPY expression in the DMN and VMN with no feedback from body fat content. Negative feedback control by body fat content on ARC neuropeptide expression is present in young animals but vanishes with age and is modulated by MC4R deficiency.


Long-term efficacy and safety of Chinese made sirolimus eluting stents: results, including off label usage, from two centres over three years.
Multiple randomized clinical trials have demonstrated that drug eluting stents can significantly reduce the rates of restenosis and subsequent adverse events across lesion and patient. We investigated the medium term clinical efficacy and safety of Firebird sirolimus eluting stent (SES) in coronary artery disease. The sample was 509 consecutive patients with coronary artery disease (CAD) who were treated by Firebird SES and finished three-year clinical follow-up. The occurrences of major adverse cardiac events (MACE) and Academic Research Consortium defined stent thrombosis (ST) were evaluated in patients with and without diabetes mellitus. Three hundred and thirty three patients (65.4%) were treated by Firebird SES by off label indications. Angiographic success was achieved in 98.3% of the lesions. MACE and target vessel revascularization rates at 6-month, 1 year's and 3 years' clinical follow-up were 2.4% and 1.4%, 4.1% and 2.8%, 7.9% and 5.1%, respectively. The cumulative 3-year MACE free survival rate was 92.1%. After 3 years, DM patients had significantly higher rates of MACE (13.7% vs 6.4%, P < 0.05) and TVR (9.8% vs 4.0%, P < 0.05) and the cumulative MACE free survival rate was very significantly lower in the DM group (86.4% vs 93.6%, P < 0.05). ST occurred in 7 patients (1.4%) at the end of 3 years' follow-up, 5 of them had definite ST with 4 cases presenting with myocardial reinfarction and 1 with unstable angina, the other 2 with probable ST had reinfarction in the stented coronary territory without angiographic follow-up. There was no difference in occurrence of ST between off label (1.5%) and on label groups (1.1%, P = 0.07). In daily practice, about 2/3 of patients were treated by Firebird SES by off label indications. Medium term clinical follow-up of 3 years indicated CAD patients treated by Firebird SES had a low MACE and acceptable ST rate. DM patients had higher rates of adverse events and than non DM.


Intraocular pressure in schizophrenic patients treated with psychiatric medications.
In order to assess the occurrence of adverse ocular effects of antipsychotic drugs, we sought to evaluate intraocular pressure of schizophrenic patients treated with psychiatric medications. Twenty-eight outpatients with DSM-IV diagnosis of schizophrenia who met both the inclusion and exclusion criteria were submitted to an ophthalmic evaluation for ocular abnormalities which included intraocular pressure measurement with Goldmann applanation tonometry. Raised intraocular pressure was found in three patients (11%). Abnormality in cup-disc ratio was seen in only one patient with cup-disc ratio asymmetry of 0.4. All these four patients were taking only ziprasidone. Patients using ziprasidone were found to have abnormalities in both intraocular pressure and cup-disc ratio.


Saccharomyces cerevisiae multidrug resistance transporter Qdr2 is implicated in potassium uptake, providing a physiological advantage to quinidine-stressed cells.
The QDR2 gene of Saccharomyces cerevisiae encodes a putative plasma membrane drug:H(+) antiporter that confers resistance against quinidine, barban, bleomycin, and cisplatin. This work provides experimental evidence of defective K(+) (Rb(+)) uptake in the absence of QDR2. The direct involvement of Qdr2p in K(+) uptake is reinforced by the fact that increased K(+) (Rb(+)) uptake due to QDR2 expression is independent of the Trk1p/Trk2p system. QDR2 expression confers a physiological advantage for the yeast cell during the onset of K(+) limited growth, due either to a limiting level of K(+) in the growth medium or to the presence of quinidine. This drug decreases the K(+) uptake rate and K(+) accumulation in the yeast cell, especially in the Deltaqdr2 mutant. Qdr2p also helps to sustain the decrease of intracellular pH in quinidine-stressed cells in growth medium at pH 5.5 by indirectly promoting H(+) extrusion affected by the drug. The results are consistent with the hypothesis that Qdr2p may also couple K(+) movement with substrate export, presumably with quinidine. Other clues to the biological role of QDR2 in the yeast cell come from two additional lines of experimental evidence. First, QDR2 transcription is activated under nitrogen (NH(4)(+)) limitation or when the auxotrophic strain examined enters stationary phase due to leucine limitation, this regulation being dependent on general amino acid control by Gcn4p. Second, the amino acid pool is higher in Deltaqdr2 cells than in wild-type cells, indicating that QDR2 expression is, directly or indirectly, involved in amino acid homeostasis.


Risperidone in Elderly Schizophrenic Patients: An Open-Label Trial.
The authors assessed the safety and efficacy of risperidone in a group of elderly patients with chronic schizophrenia and behavioral disturbances (N = 10). There were no clinically significant changes on physical examination. Also, schizophrenic symptoms and cognitive performance improved during risperidone administration. Patients showed a sufficient improvement in both areas to warrant a larger, double-blind study assessing the effects of risperidone on cognitive and psychiatric symptoms in elderly psychotic patients.


A microcosm study on bioremediation of p-nitrophenol-contaminated soil using Arthrobacter protophormiae RKJ100.
p-Nitrophenol (PNP), a toxic nitroaromatic compound, can build up in soils due to extensive usage of nitrophenolic pesticides and hence needs to be removed. Arthrobacter protophormiae RKJ100, a PNP-degrading organism, was used in this work to study factors affecting its growth, and then evaluated for its capacity to degrade PNP in soil microcosms. Molasses (10%) treated with 0.1% potassium hexacyanoferrate was found to be a suitable and cheap carbon source for inoculum preparation. Induction studies showed that PNP depletion was quicker when cells were induced by pre-exposure to PNP. The efficiency of PNP degradation in soil by strain RKJ100 was seen to be dependent on pH, temperature, initial PNP concentration and inoculum size. Microcosm studies performed with varying concentrations (1.4-210 ppm) of PNP-spiked soils showed that strain RKJ100 could effectively degrade PNP over the range 1.4-140 ppm. A cell density of 2x10(8) colony forming units/g soil was found to be suitable for PNP degradation over a temperature range of 20-40 degrees C and at a slightly alkaline pH (7.5). Our results indicate that strain RKJ100 has potential for use in in situ bioremediation of PNP-contaminated sites. This is a model study that could be used for decontamination of sites contaminated also with other compounds.


Skin-temperature distribution under a new type of defibrillating electrode.
The temperature rises under a new type of x-ray-transparent, improved current-density-distribution defibrillation electrode applied to pig skin were measured at four sites with fiberoptic thermal probes. Three anesthetized pigs, ranging in weight from 79 to 92 lb, were used. Temperature-time curves were obtained and the maximum temperature was identified. For 17 measurements at each site, the maximum temperature rise for a 360-joule shock was 317.3 +/- 53.0 millidegrees Celsius.


Acute Hemothorax Causing Hemorrhagic Shock Following Small-bore Thoracocentesis in a Patient on Clopidogrel: A Case Report and Literature Review.
Clopidogrel is one of the most commonly prescribed thienopyridines used postcoronary stenting for acute coronary syndrome (ACS). There have been several concerns regarding performing small-bore thoracocentesis on patients on clopidogrel in our practice. We present an 85-year-old male with a history of diabetes, atrial fibrillation, diastolic heart failure, chronic kidney disease (CKD) stage three, who recently had a non-ST elevation myocardial infarction (NSTEMI) requiring a drug-eluting stent (DES) to the left anterior descending (LAD) artery, and was on dual anti-platelet therapy (DAPT). He was admitted with worsening shortness of breath and found to have bilateral pleural effusions. He required several small-bore, ultrasound-guided thoracocentesis on the right side while on clopidogrel. Intensivists or residents did all the procedures. The patient went into a hemorrhagic shock following his third small-bore thoracocentesis, requiring pressors, blood and platelet transfusions, and a surgical intercostal (IC) drain insertion. He eventually became clinically stable. An IC arteriogram within 24 h ruled out IC artery injury. Healthcare professionals perceive small-bore thoracocentesis as a safe procedure done on medical, surgical, intensive care, and interventional radiology (IR) units. The overall consensus is that it is safe to perform it on patients taking clopidogrel. We emphasize through this case report the bleeding risks associated with performing such procedures on patients while on clopidogrel and considering holding clopidogrel when feasible or bridging with an intravenous anti-platelet drug.


Patterns of glomerulonephritis in Zimbabwe: survey of disease characterised by nephrotic proteinuria.
Ninety-eight Zimbabweans with glomerulonephritis characterised by nephrotic proteinuria were studied. There was no evidence to implicate Schistosoma mansoni or S. haemotobium in the aetiology, although schistosomiasis was diagnosed in 54 patients in the series. Similarly, Plasmodium malariae proved unimportant as a cause of the nephrotic syndrome, only one patient showing focal segmental glomerulosclerosis which was associated with subclinical quartan malarial infection. Nevertheless, infections were shown to play a major role in the genesis of glomerulonephritis which was associated with beta-haemolytic streptococcal, hepatitis B and syphilitic infection in 45 patients in the series. The major patterns of disease in childhood proved to be membranous glomerulopathy associated with hepatitis B antigenaemia. In young adults post-streptococcal proliferative glomerulonephritis constituted the commonest disease pattern. In older adult patients a miscellany of primary and secondary glomerulonephritides was encountered but proliferative glomerulonephritis, which was both idiopathic and streptococcus-related, predominated.


Recording ERGs and VERs from unsedated children.
A technique for recording the electroretinogram and visual evoked response from very young or mentally retarded children without general anesthesia is presented. Illustrative results from both normal and abnormal subjects are shown. The advantages to the patient of avoiding general anesthesia in reduced risk, time, and especially expense are discussed.


Inherently Chiral Upper-Rim-Bridged Calix[4]arenes Possessing a Seven Membered Ring.
The mercuration of calix[4]arene immobilized in the cone conformation allowed the introduction of an amino group at the meta position of the basic skeleton. Acylation and subsequent intramolecular Bischler-Napieralski-type cyclization led to a novel type of bridged calixarene containing a seven-membered ring. These compounds with an enlarged and rigidified cavity represent a unique and inherently chiral system that may potentially be applicable for the design of chiral receptors. The absolute configuration of one enantiomer, obtained by resolution of the racemate using chiral HPLC, was assigned by single-crystal structure determination.


A bite difficult to heal: Pasteurella multocida induced decompensated hepatic cirrhosis.
Pasteurella multocida is a gram-negative bacterium that colonizes domestic animals. It is commonly implicated in bite and scratch wounds, potentially resulting in cellulitis, superficial abscesses, osteomyelitis, or peritonitis. Rarely, it can lead to bacteremia and septic shock in high-risk patients. We present an atypical presentation of Pasteurella multocida bacteremia and sepsis in a patient with stage 4 decompensated cirrhosis. The patient presented with melena and altered mental status with CT imaging showing a heterogeneous nodular liver along with an enlarged portal vein, gastric varices, and ascites consistent with decompensated cirrhosis. The patient was initially managed with intravenous (IV) octreotide and pantoprazole, blood and platelet transfusions, and broad-spectrum antibiotics. Upper endoscopy showed diffuse non-bleeding esophageal and gastric varices, which required band ligation and continued IV octreotide therapy. The infection resolved after a 7-day course of IV ceftriaxone.


[Is a repeat treatment of antibiotic therapy necessary?].
Interrelations between host, bacterium and antibiotic compound in antibiotic therapy of bacterial infections are analysed. Some methods for the evaluation of antibacterial activity of antibiotics in vitro are described and their limits, in particular of the widely used MIC tests, are demonstrated. Data from trials comparing antibiotic applications once and twice a day as well as discussions in chemotherapy, concerning the applicability of in vitro results to therapy, are used to try to find practicable guidelines for the repetition of antibiotic therapy.


Positioning hydrogen reaction sites by constructing CdS/CoNiMoS4 heterojunctions for efficient photocatalytic hydrogen evolution.
The high gravimetric energy density of hydrogen makes it an ideal chemical fuel to address the issues of fossil fuel depletion and environmental pollution. Even though transition metal sulfides (TMSs) have been extensively investigated as substitutes for noble metals, their effectiveness is still doubtful for practical applications. Herein, we introduce a facile and general strategy to fabricate heterojunctions with CdS nanorods and a multimetallic transition metal sulfide (CoNiMoS4) for enhanced photocatalytic activity. The CdS/CoNiMoS4 heterojunction will serve as a dual-function photocatalyst with enhanced visible light absorption capability offered by CdS and high charge transfer efficiency provided by CoNiMoS4 nanostructures. Moreover, CdS/CoNiMoS4 nanostructures exhibit the best photocatalytic performance to generate H2 with an amount of 31.9 mmol g-1 h-1, with a distinguished stability for over 25 h. This synthetic approach may offer a new strategy to create diverse heterojunctions with Earth-abundant multimetallic components, which may broaden their scope of application in catalysis.


The effects of swimming exercise and supraphysiological doses of nandrolone decanoate on the testis in adult male rats: a transmission electron microscope study.
Anabolic-androgenic steroids (AAS) are used in high doses by athletes to improve athletic ability, physical appearance, and muscle mass. Unfortunately, the abuse of these agents has significantly increased. It has been established that exercise and high doses of AAS may influence the hypothalamic-pituitary gonadal (H-P-G) axis, which can in turn affect the ultrastructure of the testes. However, the effect of the combination of exercise and high doses of AAS on the ultrastructure of the testes is not known. This study was undertaken in order to examine the combination effects of swimming exercise and supraphysiological doses of nandrolone decanoate on the ultrastructural changes in rat testes. Five groups of male Wistar strain albino rats were treated as follows for 8 weeks: solvent of nandrolone decanoate (peanut oil) as a vehicle (sham); nandrolone decanoate (ND) (10 mg/kg/week) - ND; exercise (1 h/day, 5 days a week) - exercise; ND (10 mg/kg/week) and exercise (1 h/day, 5 days a week) - ND-EX; and sedentary control without any injection or exercise - control. Ultrastructural changes in the rat testes were characterised by transmission electron microscopy. The number and size of Leydig cells were considerably decreased in the interstitial space in the experimental rats. The increased thickness and irregular wavy multilaminar appearance of basement membrane in the treated animals, especially in the ND-EX group, are associated with well developed myoid cells. Cytoplasm vacuolisation, vesicular-like crista of the mitochondria, numerous lipid droplets, and lysosome and phagolysosome in Sertoli cells were significantly observed in the experimental groups. Several apoptotic germ cells were considerably observed in the experimental rats (p ≤ 0.05). Exercise training seems to increase the extent of ultrastructural changes caused by supraphysiological doses of ND in rats, which in turn may affect fertility.