Biological homing: hypothesis for a quantum effect that leads to the existence of life.
In biological systems, complex molecules interact with specificity and rapidity. The hypothesis is advanced that there are complementary sites on the surfaces of pairs of biological molecules with an enhanced attraction due to quantum mechanics. I postulate that a biological homing effect arises from the quantum mechanical probability that complementary pairs of molecules will join, and that this phenomenon is the force that drives biology and gives rise to the existence of life. To illustrate the approach, a simplified calculation is given for the interaction cross-section between two molecules, each with N surface charges that have an identical spatial distribution but with paired charges having opposite signs. The resulting cross-section is enhanced by a factor of N2 over the coulomb-scattering cross-section for a single pair of charges. We hypothesize that the existence of life is a direct and inevitable consequence of the principles presented here.


A novel antigen defined by monoclonal antibody CR101 is associated with small cell lung carcinoma.
Small cell lung carcinoma (SCLC) represents about 25% of all lung cancers. Human SCLC shows neuroendocrine features such as the production of neural peptide hormones, marker enzymes and neurosecretory granules, and the expression of neural cell adhesion molecules (NCAMs). Although SCLC is sensitive to both chemotherapy and radiation, prognosis remains poor due to the appearance of post-treatment chemo- and radioresistant variants. Monoclonal antibodies (MAbs) have been developed that bind to SCLC tumor antigens. We have used similar technology to define another SCLC marker designated gP94/115. The MAb CR101 binds to a highly glycosylated, cell-surface antigen associated with SCLC. In vitro expression of the antigen appears to be restricted to cell lines of SCLC origin. Enzymatic removal of the sugars resolves the antigen into two proteins of 94 and 115 kD by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Fluorescence-activated cell sorting (FACS) analysis confirms the antibody's specificity. These results indicate that CR101 may recognize a novel protein expressed by SCLC.


[A modified nasal tamponade with foam rubber protection in epistaxis].
We present a modification of a nosebleed catheter or nasal/nasopharyngeal tamponade in case of bleeding from the posterior nasal cavity. A piece of foam rubber from a "moist nose" is cut to size and drawn over the tamponade. The advantage of the method is that it protects the sides of the patient's nose against pressure ulcers and prevents the tamponade from sliding into the naso/oropharynx. Treatment would be meaningfully complemented by continuous intravenous sedation of the patient by combining a peripheral with a central analgesic.


Marked downregulation of the granulopoiesis regulator LEF1 is associated with disease progression in the myelodysplastic syndromes.
Lymphoid enhancer-binding factor 1 (LEF1) is a neutrophilic granulopoiesis regulator whose absence is critical in congenital neutropenia. We have shown LEF1 downregulation in the CD34(+) cells of the majority of myelodysplastic syndromes (MDS) patients. LEF1 was the most significant differentially expressed gene between early and advanced MDS. Marked LEF1 downregulation was found in 27/32 patients with advanced MDS and in 6/35 patients with early MDS, and was associated with neutropenia. Downregulation of LEF1 mRNA was reflected at the protein level. Immunostaining for CD34/LEF1 may represent a marker of advanced MDS. LEF1 may play a role in the defective maturation of myeloid progenitors in MDS.


Biomechanical performance of orthopedic gloves.
The purpose of this study was to compare the biomechanical performance of commercially available orthopedic gloves to that of a single surgical glove, as well as a double glove system. The orthopedic gloves were found to be thicker than the single surgical glove. This increased thickness of the orthopedic glove was associated with a greater resistance to glove puncture. The thickest orthopedic gloves also had reduced tactile sensitivity when compared to the single surgical glove. In addition, the glove donning forces and glove hydration rates varied considerably. These latter biomechanical performance parameters were not significantly related to glove thickness. The double glove systems tested in this study had similar performance characteristics in regard to many of the orthopedic gloves. The glove donning forces for the double glove systems were the lowest of the gloves tested. In addition, the double glove systems displayed the greatest resistance to glove hydration of the gloves tested. Their performance in the glove hydration tests and the force required to don the double glove systems were much more desirable than any of the orthopedic gloves. The results of this study indicate that the double glove systems may provide a desirable alternative to the use of the single orthopedic gloves.


Developmentally regulated activity of CRM1/XPO1 during early Xenopus embryogenesis.
In this work, we have investigated the role of CRM1/XPO1, a protein involved in specific export of proteins and RNA from the nucleus, in early Xenopus embryogenesis. The cloning of the Xenopus laevis CRM1, XCRM1, revealed remarkable conservation of the protein during evolution (96.7% amino acid identity between Xenopus and human). The protein and mRNA are maternally expressed and are present during early embryogenesis. However, our data show that the activity of the protein is developmentally regulated. Embryonic development is insensitive to leptomycin B, a specific inhibitor of CRM1, until the neurula stage. Moreover, the nuclear localization of CRM1 changes concomitantly with the appearance of the leptomycin B sensitivity. These data suggest that CRM1, present initially in an inactive form, becomes functional before the initiation of the neurula stage during gastrula-neurula transition, a period known to correspond to a critical transition in the pattern of gene expression. Finally, we confirmed the gastrula-neurula transition-dependent activation of CRM1 by pull-down experiments as well as by the study of the intracellular localization of a green fluorescent protein tagged with a nuclear export signal motif during early development. This work showed that the regulated activity of CRM1 controls specific transitions during normal development and thus might be a key regulator of early embryogenesis.


Childhood trauma and dissociative symptoms in panic disorder.
Childhood trauma has been associated with increased risk for both panic disorder and dissociative symptoms in adulthood. The authors hypothesized that among individuals with a primary diagnosis of panic disorder, those experiencing depersonalization/derealization during panic attacks would be more likely to have a history of childhood trauma. Rates of traumatic events were compared between panic disorder patients with (N=34) and without (N=40) prominent depersonalization/derealization during panic attacks. Symptom severity in the two groups was also examined. Contrary to the authors' hypothesis, no evidence was found that depersonalization/derealization during panic attacks was associated with childhood trauma. Minimal differences in severity of illness were found between patients with dissociative symptoms and those without such symptoms. This finding is consistent with a multifactorial model of dissociation. Factors other than childhood trauma and general psychopathology may underlie vulnerability to dissociative symptoms in panic disorder.


Can clinicians accurately assess esophageal dilation without fluoroscopy?
This study questioned whether clinicians could determine the success of esophageal dilation accurately without the aid of fluoroscopy. Twenty patients were enrolled with the diagnosis of distal esophageal stenosis, including benign peptic stricture (17), Schatski's ring (2), and squamous cell carcinoma of the esophagus (1). Dilation attempts using only Maloney dilators were monitored fluoroscopically by the principle investigator, the physician and patient being unaware of the findings. Physicians then predicted whether or not their dilations were successful, and they examined various features to determine their usefulness in predicting successful dilation. They were able to predict successful dilation accurately in 97% of the cases studied; however, their predictions of unsuccessful dilation were correct only 60% of the time. Features helpful in predicting passage included easy passage of the dilator (98%) and the patient feeling the dilator in the stomach (95%). Excessive resistance suggesting unsuccessful passage was an unreliable feature and was often due to the dilator curling in the stomach. When Maloney dilators are used to dilate simple distal strictures, if the physician predicts successful passage, he is reliably accurate without the use of fluoroscopy; however, if unsuccessful passage is suspected, fluoroscopy must be used for confirmation.


Type III syndactyly and oculodentodigital dysplasia: a clinical spectrum.
A newborn male patient presented with complete cutaneous syndactyly of fingers 3-5 in the left hand and fingers 4-5 in the right hand. The mother and maternal grandmother were born with the same hand malformation. Facial features in the mother showed a thin nose and small teeth; eyes were normal. In the grandmother, teeth had been very small with enamel hypoplasia; eyes were normal. The present family provides evidence of the variable expression in oculodentodigital dysplasia. Inheritance is autosomal dominant.


PDGF-BB protects mitochondria from rotenone in T98G cells.
Rotenone is one of the most-studied neurotoxic substances as it induces oxidative stress processes both in cellular and animal models. Rotenone affects ATP generation, reactive oxygen species (ROS) production, and mitochondrial membrane potential in neurons and astrocyte-like cells. Previous epidemiologic studies have supported the role of neurotrophic factors such as BDNF and GDNF in neuroprotection mainly in neurons; however, only very few studies have focused on the importance of astrocytic protection in neurodegenerative models. In the present study, we assessed the neuroprotective effects of PDGF-BB against toxicity induced by rotenone in the astrocytic-like model of T98G human glioblastoma cell line. Our results demonstrated that pretreatment with PDGF-BB for 24 h increased cell viability, preserved nuclear morphology and mitochondrial membrane potential following stimulation with rotenone, and reduced ROS production nearly to control conditions. These observations were accompanied by important morphological changes induced by rotenone and that PDGF-BB was able to preserve cellular morphology under this toxic stimuli. These findings indicated that PDGF-BB protects mitochondrial functions, and may serve as a potential therapeutic strategy in rotenone-induced oxidative damage in astrocytes.


Class-, gene-, and group-specific HLA silencing by lentiviral shRNA delivery.
HLA incompatibility is the most relevant immunologic barrier to cell-based therapies. Improvement of histocompatibility is essential to achieving better survival of allogeneic cells in the foreign organism. RNA interference technology can be used to selectively and stably reduce cellular HLA class I expression. In the present study, we designed small interfering RNA (siRNA) molecules that target either beta2-microglobulin (beta2m) or HLA-A heavy chain transcripts and identified sensitive sites on the target RNAs using an in vitro transcription/translation (IVTT) system. Transfection of siRNA into B-lymphocyte cell lines (B-LCLs) resulted in specific reduction of HLA class I or HLA-A antigen expression by 79% at the mRNA and protein levels. An allele-specific HLA silencing rate of 65% was achieved in a B-LCL heterozygous for HLA-A*24,*68 allospecificities using HLA-A*68-specific siRNA. Lentiviral delivery of short hairpin RNA into HeLa and B-LCL cells resulted in selective and permanent silencing of HLA class I or HLA-A by up to 90% even under inflammatory conditions. In cytotoxicity and proliferation assays, it was demonstrated that HLA class I knockdown was effective in preventing antibody-mediated cell lysis and CD8+ T cell response, while the residual HLA expression in HLA-silenced cells was protective against NK-cell-mediated lysis. The present data strongly suggest that silencing of HLA expression in a class-, gene-, and group-specific manner is an effective approach that may provide a new basis for developing new immunotherapies in the field of regenerative medicine.


Antenna-coupled photon emission from hexagonal boron nitride tunnel junctions.
The ultrafast conversion of electrical signals to optical signals at the nanoscale is of fundamental interest for data processing, telecommunication and optical interconnects. However, the modulation bandwidths of semiconductor light-emitting diodes are limited by the spontaneous recombination rate of electron-hole pairs, and the footprint of electrically driven ultrafast lasers is too large for practical on-chip integration. A metal-insulator-metal tunnel junction approaches the ultimate size limit of electronic devices and its operating speed is fundamentally limited only by the tunnelling time. Here, we study the conversion of electrons (localized in vertical gold-hexagonal boron nitride-gold tunnel junctions) to free-space photons, mediated by resonant slot antennas. Optical antennas efficiently bridge the size mismatch between nanoscale volumes and far-field radiation and strongly enhance the electron-photon conversion efficiency. We achieve polarized, directional and resonantly enhanced light emission from inelastic electron tunnelling and establish a novel platform for studying the interaction of electrons with strongly localized electromagnetic fields.


Metal ion-mediated assembly of DNA nanostructures for cascade fluorescence resonance energy transfer-based fingerprint analysis.
Contamination of heavy metal ions in an aquatic environment poses a serious threat to human health. More seriously, heavy metal ions are usually present in the environment in a mixture, and the synergetic toxicity of multiple heavy metal ions is revealed (Aragay et al. Chem. Rev. 2011, 111, 3433; Chu et al. Aquat. Toxicol. 2002, 61, 53). Unfortunately, most of the existing methods based on DNA sequences are focusing on the detection of one type of metal ions. Simple and multiplexed detection of multiple metal ions has been poorly investigated and remains challenging. Here, we re-engineered the DNA sequences for Pb(2+), Hg(2+), and Ag(+), through which the binding of multiple metal ions initiated the self-assembly of these DNA sequences. On the basis of our rationally designed multicolor fluorescent labeling of the DNA sequences, cascade fluorescence resonance energy transfer (FRET) occurred. As a result, a fingerprint fluorescent spectrum was produced to indicate the presence of a single type of metal ions or multiple metal ions. The major advantages of our cascade FRET fingerprint technology include the following: (1) the "mix and read" detection mode in homogeneous solution is simple without the need of complicated instruments; (2) only single excitation is required to provide the cascade FRET fingerprint spectrum; (3) multiplexed detection capability can be realized intuitively and sensitively.


Myopathy in patients with Hashimoto's disease.
Hashimoto thyroiditis (HT) is an autoimmune disease of the thyroid gland. Patients may present or not a hypothyroid state, and frequently have manifestations of myopathy. The present work was aimed to assess the clinical symptoms and signs of skeletal muscle alterations in HT, describe the muscular pathological changes and relate them to the functional thyroid status and to the autoimmune condition of the patient. Clinical and laboratory studies were performed in ten HT patients and three control subjects (hormonal levels and electromyography). Biopsies from their vastus lateralis of quadriceps femoris muscle were analyzed under light (histochemistry and immunofluorescense) and electron microscopy. All patients showed muscle focal alterations, ranging from moderate to severe atrophy, necrosis, activation of satellite cells, presence of autophagosomes, capillary alterations and macrophage and mast cell infiltration, common to autoimmune diseases. The intensity of clinical signs and symptoms was not related to the morphological muscle findings, the electromyography results, or to the state of the thyroid function. Reactions for immunoglobulin in muscle fibers were positive in 80% of the patients. Fiber type II proportion was increased in all patients, with the exception of those treated with L-thyroxine. In conclusion, autoimmune processes in several of the patients may be associated to the skeletal muscle alterations, independently of the functional state of the thyroid gland; however, fiber II type proportion could have been normalized by L-thyroxine treatment.


Phase 2 study of S-1 and carboplatin plus bevacizumab followed by maintenance S-1 and bevacizumab for chemotherapy-naive patients with advanced nonsquamous non-small cell lung cancer.
A previous phase 3 trial demonstrated noninferiority in terms of overall survival for combined S-1 (an oral fluoropyrimidine) and carboplatin compared with combined paclitaxel and carboplatin as first-line treatment for advanced non-small cell lung cancer (NSCLC). In the current study, the authors evaluated the efficacy and safety of combined S-1, carboplatin, and bevacizumab followed by maintenance with S-1 and bevacizumab in chemotherapy-naive patients with advanced nonsquamous NSCLC. Patients received carboplatin (area under the concentration-time curve, 5 mg mL(-1) per minute) and bevacizumab (15 mg/kg) on day 1 plus oral S-1 (80 mg/m2 per day) on days 1 through 14 every 21 days for up to 6 cycles. For patients without disease progression, S-1 and bevacizumab were continued until disease progression or unacceptable toxicity developed. Forty-eight patients were enrolled in the phase 2 study; of these, 35 patients (72.9%) completed at least 4 cycles. Most toxicities of grade ≥3 were hematologic, and no increase in relative incidence associated with maintenance with S-1 and bevacizumab was observed. The objective response rate was 54.2% (95% confidence interval, 39.2%-68.6%), and the median progression-free survival was 6.8 months (95% confidence interval, 4.3-8.2 months). The regimen of combined S-1, carboplatin, and bevacizumab followed by maintenance with S-1 and bevacizumab was active and feasible as first-line treatment for advanced nonsquamous NSCLC.


Localization of alpha-interferon in the human feto-placental unit.
The distribution of alpha-interferon in human placental tissue was investigated by immunocytochemical study of paraffin wax-embedded tissue sections using a sheep alpha-interferon antiserum. Fifty-eight placentas of gestational ages from 8 to 40 weeks were examined. alpha-Interferon was present in the syncytiotrophoblast of the chorionic villi of all placentas and was also in macrophages in 28 cases. The appearances suggest production of interferon in human placental trophoblast and, in view of its diverse biological effects, support the concept of a role for alpha-interferon in the complex series of events required for successful gestation.


Effects of verapamil on (Na+ + K+)-ATPase, Ca2+-ATPase, and adenylate cyclase activity in a membrane fraction from rat and guinea pig ventricular muscle.
The electrophysiologic properties and the negative inotropic effect of verapamil are most likely due to the inhibition of calcium movement across the sarcolemmal membrane. A possible biochemical basis for this inhibition of calcium movement was studied in a membrane fraction rich in (Na+ + K+)-ATPase (EC 3.6.1.3) and adenylate cyclase (EC 4.6.1.1) activity and which demonstrated Ca2+-ATPase (EC 3.6.1.3) activity. Since each of these enzymes has the potential for influencing transsarcolemmal calcium movements, the effect of verapamil on their activities was studied in this membrane fraction isolated from rat and guinea pig hearts. Ca2+-ATPase activity in the rat was 37.7 mumol Pi/mg per hour compared with 13.8 +/- 2.9 in the guinea pig (p less than 0.01). Corresponding values for (Na+ + k+)-atpase activites were 7.9 +/- 0.9 mumol Pi/mg per hour versus 10.2 +/- 1.4. Adenylate cyclase activity in the rat was 240 +/- 8 pmol/mg per minute compared with 299 +/- 27. It was found that verapamil in concentrations of 0.01-100 mg/litre (2.1 X 10(-8) to 2.1 X 10(-4) M) had no effect on the activity of the above enzymes in either species and it was concluded that a biochemical basis for the effect of verapamil on calcium flux has yet to be defined.


CT brain perfusion protocol to eliminate the need for selecting a venous output function.
In CTP, an arterial input function is used for cerebral blood volume measurement. AIFs are often influenced by partial volume effects resulting in overestimated CBV. A venous output function is manually selected to correct for partial volume. This can introduce variability. Our goal was to develop a CTP protocol that enables AIF selection unaffected by partial volume. First, the effects of partial volume on artery sizes/types including the MCA were estimated by using a CTP phantom with 9 protocols (section thicknesses of 1, 1.8, and 5 mm and image resolutions of 0.5, 1, and 1.5 mm). Next, these protocols were applied to clinical CTP studies from 6 patients. The influence of the partial volume effect was measured by comparison of the time-attenuation curves from different artery locations with reference veins. AIFs from MCAs were unaffected by partial volume effects when using high image resolution (1 mm) and medium section thickness (1.8 mm). For the clinical data, a total of 104 arteries and 60 veins was selected. The data confirmed that high image resolution and thin section thickness enable selection of MCAs for AIFs free of partial volume influences. In addition, we found that large veins were not insusceptible to partial volume effects relative to large arteries, questioning the use of veins for partial volume correction. A CTP protocol with 1.8-mm section thickness and 1-mm image resolution allows AIF selection unaffected by partial volume effects in MCAs.


[Investigation of the residue of the fasciolicide nitroxynil in milk and dairy products].
A sensitive gas chromatographic method with electron capture detection of the fasciolicide, nitroxynil, in milk and dairy products was developed and was applied to assess nitroxynil concentration in cow's milk after subcutaneous injection of three lactating cows. The level of nitroxynil in cow's milk reached a maximum (0.25-0.26 micrograms/ml) in 6-30 hours, and was undetectable within 8 weeks. Analysis of nitroxynil concentrations in cream, skimmed milk, curd and whey prepared from nitroxynil excreting cow's milk showed that the chemical became concentrated in cream and curd. Nitroxynil appeared to be stable at temperature used in LTLT and HTST pasteurization with the rate of degradation in milk being less than 10%. Investigation of nitroxynil residues in milk (raw, liquid whole, processed) and dairy products (processed cheese, natural cheese, butter, sweetened condensed milk, evaporated skimmed milk, skimmed milk powder, formulated milk powder) was performed during 1976-1979. Nitroxynil was detected in 20% of milk samples at a maximum level of 39 ng/ml, with one formulated milk powder at level of 0.34 ng/g. Confirmation of nitroxynil was performed by GCMS. The results of this investigation were promptly reported to the government. Since then administrative guidance was provided leading to appropriated use of nitroxynil thereafter. The ordinance controlling dairy production amended in 1979 revised the withdrawal time for medicines administrated to cows from "three days" to "the period when medicine remains in the milk". There was no mutagenicity of nitroxynil evident by the Ames test.


Factors influencing indomethacin toxicity in the rat.
The influence of various experimental conditions, such as nature of the diet, feeding schedule, sex and castration on indomethacin toxicity in the rat has been determined. In general, the following conclusions can be drawn: a) Independently of feeding schedule, sex or castration, indomethacin is significantly more toxic in animals on regular (RD) than in those on fat-free diet (FFD). b) Regardless of sex or castration, fasting significantly reduces indomethacin toxicity in RD fed animals. c) With the exception of RD unfasted animals, indomethacin is significantly more toxic in males than in females. d) Incidence and degree of intestinal ulceration are not sex dependent. e) Independently of the kind of diet and of the feeding schedule, castration reduces indomethacin toxicity in males but does not modify it in females. These findings are discussed.


Arterial blood pressure responses to cell-free hemoglobin solutions and the reaction with nitric oxide.
Changes in mean arterial pressure were monitored in rats following 50% isovolemic exchange transfusion with solutions of chemically modified hemoglobins. Blood pressure responses fall into three categories: 1) an immediate and sustained increase, 2) an immediate yet transient increase, or 3) no significant change either during or subsequent to exchange transfusion. The reactivities of these hemoglobins with nitric monoxide (.NO) were measured to test the hypothesis that different blood pressure responses to these solutions result from differences in .NO scavenging reactions. All hemoglobins studied exhibited a value of 30 microM-1 s-1 for both .NO bimolecular association rate constants and the rate constants for .NO-induced oxidation in vitro. Only the .NO dissociation rate constants and, thus, the equilibrium dissociation constants varied. Values of equilibrium dissociation constants ranged from 2 to 14 pM and varied inversely with vasopressor response. Hemoglobin solutions that exhibited either transient or no significant increase in blood pressure showed tighter .NO binding affinities than hemoglobin solutions that exhibited sustained increases. These results suggest that blood pressure increases observed upon exchange transfusion with cell-free hemoglobin solutions can not be the result of .NO scavenging reactions at the heme, but rather must be due to alternative physiologic mechanisms.


Markov invariants for phylogenetic rate matrices derived from embedded submodels.
We consider novel phylogenetic models with rate matrices that arise via the embedding of a progenitor model on a small number of character states, into a target model on a larger number of character states. Adapting representation-theoretic results from recent investigations of Markov invariants for the general rate matrix model, we give a prescription for identifying and counting Markov invariants for such “symmetric embedded” models, and we provide enumerations of these for the first few cases with a small number of character states. The simplest example is a target model on three states, constructed from a general 2 state model; the "2 --> 3" embedding. We show that for 2 taxa, there exist two invariants of quadratic degree that can be used to directly infer pairwise distances from observed sequences under this model. A simple simulation study verifies their theoretical expected values, and suggests that, given the appropriateness of the model class, they have superior statistical properties than the standard (log) Det invariant (which is of cubic degree for this case).


A national survey of obstetric anaesthetic handovers.
The handover of patient information between shifts enables continuity of care and increases patient safety. We surveyed UK practice during handovers in obstetric anaesthesia. A questionnaire was sent to 239 lead consultant obstetric anaesthetists to record routine practice in their unit and individual opinion about handover procedures. Responses were received from 168 anaesthetists, a 70% response rate. Handover policies were available in 10% of units. Most (76%) responding units had an allocated time for handover. In most units (76%), the duration of handover was reported as being < 15 min but the actual duration and depth of any discussion involved were not specified. Handovers were rarely documented in writing (7%). Consultant anaesthetists were most likely to be present at the morning handover and few handovers were multidisciplinary. Four percent of units reported critical incidents following inadequate handovers in the past 12 months. We identify features in handover procedures that could be improved.


Effect of retinol on fetal lamb tracheal epithelium, with and without epidermal growth factor. A model for the effect of retinol on the healing lung of human premature infants.
Twelve pairs of fetal lambs were used to test the hypothesis that the necrotizing tracheobronchitis followed by squamous metaplasia seen in premature infants who develop chronic bronchopulmonary dysplasia might be related to low retinol stores and might, therefore, be reversed by retinol supplementation. Epidermal growth factor (EGF) was used to model the growth factor stimulus initiated by chronic wounding of the airways, and retinol was used as a differentiator of proliferating cells stimulated by EGF. Saline-treated animals were used as controls, as were fetal lambs receiving retinol alone or EGF alone. The effects of EGF on tracheal and bronchial epithelium consisted of proliferation of basal and intermediate cells, necrosis and slough of lining ciliated and mucous-producing cells, followed by squamous metaplasia. In fetal lambs given retinol, plasma, liver and lung retinol levels rose and mucous producing cells were increased in number. In the presence of EGF plus retinol, differentiation of mucous-producing cells was accelerated. We believe that this fetal lamb model with low initial levels of retinol in plasma, liver and lung, treated with EGF may mimic human premature infants with chronic bronchopulmonary dysplasia, and that the addition of retinol in amounts sufficient to raise their tissue levels produces a more normal surface epithelium in conducting airways.


[Main trends in the development of modern lymphology].
At a historical approach in studying the lymphatic system the role of the method for investigation of this important drainage system of the organism is noted. Certain modern morphological methods of investigation are presented. Their high degree of informativeness+ and perspectives of their application for widening the notion of lymphology as a science are shown. Problems necessary to be solved in connection with a successful adoption into clinical practice of operative methods of lymphocorrection are determined. Concrete tasks for investigating morphology, function and pathology of lymph nodes and lymph transport are proposed.


Risk factors for pediatric asthma in the South Bronx.
We identified main asthma risk factors for children living in the South Bronx, where asthma rates are eight times higher than the national average. This case-control study enrolled 261 children at Lincoln Medical and Mental Health Center from 2002 to 2003. We questioned the mothers on medical history and home environment. The most important risk factors for asthma in the South Bronx pediatric population are Hispanic ethnicity, family history of asthma, and exposure to tobacco smoke. South Bronx children limited to breast-feeding during the first 3 months of age are less likely to develop asthma.


Early commitment to the eosinophil lineage by cultured human peripheral blood CD34+ cells: messenger RNA analysis.
Early hematopoietic progenitors expressing the CD34+ phenotype can be harvested from the peripheral blood of normal individuals. We have optimized the liquid culture of human CD34+ peripheral blood progenitors (PBPs) to achieve differentiation into a population of cells consisting almost entirely of eosinophil progenitors and maturing eosinophils. Growth of CD34+ PBPs for 28 days in the presence of the combination of IL-3, granulocyte-macrophage colony-stimulating factor, and IL-5 resulted in an almost 250-fold increase in cell number, yielding a population that contained 83% maturing eosinophils. The residual population consisted of basophils and mast cells (3% by acidic toluidine blue staining, 15.2% by flow cytometric assay for binding to high-affinity IgE receptor) and immature cells. This provides an opportunity to examine the kinetics of the acquisition of specialized mature eosinophil characteristics during eosinophil differentiation. Several host-defense and bioactive proteins are found almost exclusively in eosinophil granules. In addition, stimulated eosinophils, like neutrophils, produce copious amounts of toxic oxygen radicals. We used our culture system and the sensitive technique of reverse-transcriptase polymerase chain reaction to analyze the kinetics of production of messenger RNA transcripts encoding several eosinophil proteins, including five eosinophil granule proteins and four subunit peptides of the superoxide-generating reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in small numbers of differentiating eosinophils from peripheral blood CD34+ cells. Freshly isolated CD34+ PBPs contained transcripts for the ubiquitously present housekeeping protein phosphoglucokinase but contained no eosinophil granule protein transcripts and barely detectable amounts of some oxidase protein transcripts. On day 3 of culture, no cells recognizable by histochemical staining as eosinophils could be detected, but transcripts for all five eosinophil granule proteins were present. These transcripts increased several fold during the entire culture period. Similar kinetics were seen for all but one of the NADPH oxidase protein transcripts. However, transcripts for the p67phox NADPH oxidase protein were not detected until day 7, and functional oxidase activity did not appear until day 12. From that point, oxidase activity increased dramatically over the culture period. These studies demonstrate that commitment of CD34+ PBPs to the eosinophil lineage occurs very early, by day 3, but that further events in differentiation must take place before the appearance of histologically staining eosinophil granules and acquisition of functional oxidase capacity.


Reliability of Cybex II isokinetic evaluations of torque in post-poliomyelitis syndrome.
The aim of this study was to ascertain the reliability of isokinetic strength measurements in a population of post-poliomyelitis subjects (PPS). Eight subjects (four males and females, mean age of 47.5 +/- 10 and 56.8 +/- 16 years, respectively) were evaluated, on a weekly basis for three weeks at approximately the same time of day. During each test session the knee flexors and extensors (bilaterally, where possible) were evaluated. Subjects became familiar with the equipment prior to recording three maximal contractions at the four test velocities (1.05, 2.09, 3.14, 4.18rads.s-1). A two-minute rest period was allowed between sets of contractions. The variables of peak torque, angle of peak torque, torque at specific joint angles (0.79 and 1.05rads), total contractile work, maximum power, and average power were measured on-line with the Cybex II a system using a commercially available software package. In both muscle groups, all the variables were significantly weaker on the most affected, but testable limb (p < 0.01) in subjects where both limbs could be tested (n = 5). Peak torque and total work of the quadriceps were observed to decrease with increasing velocity of movement. The effects of velocity were less apparent in the hamstrings. Average and maximum power developed by the knee extensors and flexors increased with increasing velocity of movement. Reliability of performance over three test sessions was confirmed by the intraclass correlation coefficient (ICC) values derived from the univariate ANOVAs calculated for each of the above variables (> 0.80).(ABSTRACT TRUNCATED AT 250 WORDS)


Lip repositioning with reversible trial for the management of excessive gingival display: a case series.
Lip repositioning surgery is a largely unknown and underutilized treatment modality for excessive gingival display. It involves precise resection of maxillary mucosal tissues with reattachment of the lip in a more coronal position. This limits lip elevation on smiling and increases lip fullness. While this is an elective treatment, no reported cases have yet offered patients the ability to preview the outcome in a reversible manner. This case series presents seven patients who were successfully managed with trial, and then definitive, lip repositioning.


Management of agenesis of the vagina.
The management of 92 women with vaginal agenesis is presented. All patients were managed by a modified McIndoe procedure. Four women (4 per cent) had intraoperative or postoperative complications, but only one woman had a complication that resulted in failure of vaginal function. We advocate the McIndoe vaginoplasty as the primary technique of management for women with vaginal agenesis.


Protective effect of vinconate, a novel vinca alkaloid derivative, on glucose utilization and brain edema in a new rat model of middle cerebral artery occlusion.
1. We investigated the effect of a novel vinca alkaloid derivative, vinconate, against brain damage after focal ischemia induced by a middle cerebral artery (MCA) occlusion in rats. 2. Persistent focal ischemia was induced by 6 hr, and vinconate (50 and 100 mg/kg) was given intraperitoneally twice 10 min and 3 hr after MCA occlusion. 3. Focal ischemia produced the disturbance of glucose metabolism, the increase of water content and the impairment of protein synthesis in the surrounding occluded MCA territory. 4. Vinconate was effective in preventing marked reduction of cerebral glucose utilization in the areas surrounding the occluded MCA territory. 5. Vinconate significantly reduced an increase of water content in the surrounding the occluded MCA territory. 6. Preliminary L-[methyl-14C]methionine autoradiographic study also indicated that vinconate can partly prevent a severe impairment of protein synthesis after focal ischemia. 7. The results indicate that vinconate may ameliorate the disturbance of glucose metabolism, brain edema and the impairment of protein synthesis after persistent focal ischemia, and they also suggest that vinconate has a beneficial effect against brain damage.


Temozolomide in the treatment of solid tumours: current results and rationale for dosing/scheduling.
This review examines the current evidence for the use of temozolomide in the treatment of solid tumours. The possible molecular and clinical advantages of temozolomide are identified and the molecular mechanism of temozolomide resistance is explored. Attempts to maximise efficacy have led to manipulation of both dosage and drug scheduling and the evidence for the various strategies is reviewed. Finally, the potential role of combination therapy is considered.


"Cannonballs" and psammoma bodies: unusual cytologic features of metastatic pulmonary small-cell carcinoma in a pleural effusion.
Large three-dimensional cell aggregates and psammoma bodies are usually encountered in benign serous effusions (mesothelial hyperplasia and endosalpingiosis), mesotheliomas, and metastatic papillary carcinomas. We report a case of pulmonary small-cell carcinoma occurring in an 88-year-old woman that initially presented with a malignant pleural effusion characterized cytologically by a predominance of large three-dimensional neoplastic cell aggregates ("cannonballs"), associated with rare psammoma bodies. Although the crowded three-dimensional tumor-cell aggregates did not allow detailed cytologic examination, the diagnosis of metastatic small-cell carcinoma could be established noting the characteristic chromatin features of the occasional single neoplastic cells and the characteristic "cell-in-cell" and "stack-of-coins" arrangements of rare small clusters of neoplastic cells. Immunoperoxidase stains showing positivity of the tumor cells for CD56, synaptophysin, and TTF1 further supported this diagnosis. Endobronchial ultrasound-guided fine-needle aspiration of a mediastinal lymph node subsequently confirmed the diagnosis of pulmonary small-cell carcinoma. Metastatic pulmonary small-cell carcinoma should be considered in the differential diagnosis of serous effusions showing large three-dimensional neoplastic cell aggregates and psammoma bodies to prevent a potential diagnostic pitfall.


[Open versus laparoscopic appendectomy in children in a regional hospital in Israel].
Although laparoscopic appendectomy (LA) has already been found to be associated with greater diagnostic accuracy, less post-operative pain and shorter hospital stay as compared to open appendectomy (OA), questions remain regarding the advantages of this approach and it is still not widely practiced in children, especially in regional hospitals. This study aims to evaluate Ha'emek Medical Center's initial experience with pediatric OA and LA between July 2002 and October 2003. This study is a retrospective outcome analysis of pediatric OA and LA. Records of all children aged 0 to 14 years who underwent appendectomy for acute appendicitis, were reviewed. Operating time (OT), antibiotic treatment, analgesic needs, length of stay (LOS) and complications were analyzed and were compared between the groups. Seventy-one children with acute appendicitis underwent appendectomy in Ha'emek Medical Center between July 2002 and October 2003. Fifty-two children underwent OA and 19 underwent LA. There were no differences in age, sex, race, or stage of the appendicitis between the groups. LA took longer than OA (68 vs 37 minutes), length of stay was shorter for LA (2.8 vs 4.3 days), complications rate was not significantly different and overall hospital expenses were less for LA (NIS 5,756.95 vs. NIS 6,055.47). LA is as safe as OA and although it takes longer, recovery is faster. We, therefore, conclude that LA can be safely recommended for treating children with acute non-perforated appendicitis.


Alkaline gel electrophoresis of deoxyribonucleic acid photoreacted with trimethylpsoralen: rapid and sensitive detection of interstrand cross-links.
Restriction fragments of phage lambda and phi X174 deoxyribonucleic acid (DNA) were photoreacted with 4,5',8-trimethylpsoralen to various extents, and the amount of covalent cross-linking was determined by electron microscopy of the DNA under totally denaturing conditions. The DNA was then analyzed by electrophoresis in alkaline agarose gels. A single cross-link in a DNA molecule produced a large decrease in its electrophoretic mobility. With DNA fragments 0.3--4 kilobase pairs in size, the apparent Mr (molecular weight) of the cross-linked DNA was 2.0 +/- 0.1 times and Mr of the unreacted, single-stranded DNA. A single cross-link in a larger DNA molecule resulted in an even greater increase in apparent Mr. Further cross-linking produced a decrease in the apparent Mr of the DNA, reaching a plateau at a value of 1.4 +/- 0.1 times the Mr of the unreacted, single-stranded DNA over a large range of fragment sizes (0.6--10 kilobase pairs). The apparent Mr of the cross-linked DNA was weakly dependent on the percentage of agarose in the gel. Although highly sensitive to interstrand cross-links the electrophoretic mobilities appeared to be unaffected by low levels of monoadducts (trimethylpsoralen covalently bound to one strand of the DNA). The DNA bandwidths increased by as much as 4-fold at low extents of cross-linking, presumably due to heterogeneity in the locations of the cross-links in the DNA molecules. The bands became sharp again at high levels of reaction. These observations from the basis of a new assay for interstrand DNA cross-links that is both more sensitive and more convenient than previous methods.


Use of zebrafish models to investigate rare human disease.
Rare diseases are collectively common and often extremely debilitating. Following the emergence of next-generation sequencing (NGS) technologies, the variants underpinning rare genetic disorders are being unearthed at an accelerating rate. However, many rare conditions lack effective treatments due to their poorly understood pathophysiology. There is therefore a growing demand for the development of novel experimental models of rare genetic diseases, so that potentially causative variants can be validated, pathogenic mechanisms can be investigated and therapeutic targets can be identified. Animal models of rare diseases need to be genetically and physiologically similar to humans, and well-suited to large-scale experimental manipulation, considering the vast number of novel variants that are being identified through NGS. The zebrafish has emerged as a popular model system for investigating these variants, combining conserved vertebrate characteristics with a capacity for large-scale phenotypic and therapeutic screening. In this review, we aim to highlight the unique advantages of the zebrafish over other in vivo model systems for the large-scale study of rare genetic variants. We will also consider the generation of zebrafish disease models from a practical standpoint, by discussing how genome editing technologies, particularly the recently developed clustered regularly interspaced repeat (CRISPR)/CRISPR-associated protein 9 system, can be used to model rare pathogenic variants in zebrafish. Finally, we will review examples in the literature where zebrafish models have played a pivotal role in confirming variant causality and revealing the underlying mechanisms of rare diseases, often with wider implications for our understanding of human biology.


Antiproliferative effect of gossypol and its optical isomers on human reproductive cancer cell lines.
The antiproliferative effect of gossypol and its optical isomers on various human cell lines of reproductive and nonreproductive tissue origin was studied. Various reproductive cancer cell lines of ovarian, gestational, and testicular origin were highly sensitive (IC50 values of 0.86-1.98) to gossypol. The antiproliferative action of gossypol was not restricted to reproductive cancers, as non-reproductive cancer cell lines were also equally sensitive (IC50 values of 0.69-3.55). In addition, actively proliferating untransformed cells such as fibroblasts and PHA-activated lymphocytes were also sensitive (IC50 values of 0.87-2.51). (-)-Gossypol was 3.6-12.4 times more potent than (+)-gossypol and 1.48-2.65 times more potent than (+/-)-gossypol. The most sensitive indicator of gossypol action was a decrease in DNA synthesis followed by inhibition of protein synthesis and uptake of rhodamine-123 by mitochondria as tested in an ovarian cancer cell line (OVCA 433) and a fibroblast line (Hs27). These results indicate that gossypol possesses a general nonselective antiproliferative action toward human cells in vitro. Further, the pharmacologic activity of gossypol as an antiproliferative agent is primarily attributable to its (-) isomer, which is also the active isomer as a contraceptive.


Leisure-time physical activity and sports in the Brazilian population: A social disparity analysis.
To estimate the prevalence of leisure-time physical activity (LTPA) or sports in the Brazilian population according to demographic and income variables. Data from 60,202 Brazilian individuals (18 years and over) were analyzed, belonging to the National Health Survey 2013 sample. The prevalence of different modalities of LTPA and sports was estimated according to age, sex, skin color and income. The adjusted prevalence ratios were estimated by Poisson regression. Of every thousand Brazilians, 695 do not practice LTPA or sports. Walking is the most practiced LTPA (98/1000), followed by soccer (68/1000) and weight training (45/1000). For poor and black men, the most frequent LTPA was soccer, and, for women, gymnastics and walking. The prevalence of weight training and gymnastics was higher for white people compared with black people. All LTPA practices were more prevalent in individuals with higher income, except for soccer. Running on a treadmill and weight training had, respectively, 24.7 and 6.4 times higher prevalence in the richer quartile. The study allowed identifying the type of LTPA and sport reported as the most frequent by the Brazilian population according to age, sex, skin color, and income, detecting strong social disparities in these practices.


Evidence against infection with hantaviruses among forest and park workers in the southwestern United States.
To determine if individuals with extensive exposure to rodent habitats were infected with Sin Nombre hantavirus (SNV), we evaluated forest and park service personnel from the region of endemicity in the southwestern United States. Information about work and recreational activities, including exposure to rodents and a history of recent illnesses, was obtained via a standardized questionnaire. Serum specimens were also collected. Of 140 participating workers, 84 (60%) were primarily engaged in outdoor work activities, 14 (10%) were office-based supervisors, and 42 (30%) were office workers. Of the 140 employees, 89 (64%) reported repeated exposures to rodents, rodent nests, and/or rodent droppings; 22 (16%) reported trapping or handling wild rodents. Hantavirus antibodies were not detected in any park employee. These data suggest that transmission of SNV is a rare event even among persons in the southwestern United States who have a high level of exposure to this virus. Although park employees and visitors in this region are at low risk of infection with SNV, these persons should continue to use recommended measures for risk reduction.


Electronic structures of [1 1 1]-oriented free-standing InAs and InP nanowires.
We report on a theoretical study of the electronic structures of the [1 1 1]-oriented, free-standing, zincblende InAs and InP nanowires with hexagonal cross sections by means of an atomistic sp(3)s*, spin-orbit interaction included, nearest-neighbor, tight-binding method. The band structures and the band state wave functions of these nanowires are calculated and the symmetry properties of the bands and band states are analyzed based on the C(3v) double point group. It is shown that all bands of these nanowires are doubly degenerate at the Γ-point and some of these bands will split into non-degenerate bands when the wave vector k moves away from the Γ-point as a manifestation of spin-splitting due to spin-orbit interaction. It is also shown that the lower conduction bands of these nanowires all show simple parabolic dispersion relations, while the top valence bands show complex dispersion relations and band crossings. The band state wave functions are presented by the spatial probability distributions and it is found that all the band states show 2π/3-rotation symmetric probability distributions. The effects of quantum confinement on the band structures of the [1 1 1]-oriented InAs and InP nanowires are also examined and an empirical formula for the description of quantization energies of the lowest conduction band and the highest valence band is presented. The formula can simply be used to estimate the enhancement of the band gaps of the nanowires at different sizes as a result of quantum confinement.


Effects of salinity on the survival of non-O1 Vibrio cholerae under environments of low temperature.
Under low temperature conditions, the effects of survival and growth of non-O1 Vibrio cholerae were studied in laboratory microcosms. As the environmental factors, various concentrations of NaCl solution and that of mono- and bivalent cation added nutrient of polypeptone were used under several temperatures. The results of these experiments suggested an extended survival of non-O1 V. cholerae at low temperature. When a range of NaCl concentration in microcosms water was between 0.4% and 2.0% with absent of nutrient, the survival of this organism was good under the temperature from 10 degrees C to 20 degrees C. With added nutrient, when about 10 mM bivalent cation and over 0.3% NaCl co-existed, this strain was able to grow at 10 degrees C, and showed good survival. This finding suggested the possibility of survival under 10 degrees C.


Trehalose lipid biosurfactants produced by the actinomycetes Tsukamurella spumae and T. pseudospumae.
Actinomycetales are known to produce various secondary metabolites including products with surface-active and emulsifying properties known as biosurfactants. In this study, the nonpathogenic actinomycetes Tsukamurella spumae and Tsukamurella pseudospumae are described as producers of extracellular trehalose lipid biosurfactants when grown on sunflower oil or its main component glyceryltrioleate. Crude extracts of the trehalose lipids were purified using silica gel chromatography. The structure of the two trehalose lipid components (TL A and TL B) was elucidated using a combination of matrix-assisted laser desorption/ionization time-of-flight/time-of-flight/tandem mass spectroscopy (MALDI-ToF-ToF/MS/MS) and multidimensional NMR experiments. The biosurfactants were identified as 1-α-glucopyranosyl-1-α-glucopyranosid carrying two acyl chains varying of C4 to C6 and C16 to C18 at the 2' and 3' carbon atom of one sugar unit. The trehalose lipids produced demonstrate surface-active behavior and emulsifying capacity. Classified as risk group 1 organisms, T. spumae and T. pseudospumae hold potential for the production of environmentally friendly surfactants.


Current issues in the development of a vaccine to prevent human immunodeficiency virus: insights from the society of infectious diseases pharmacists.
Infection with the human immunodeficiency virus (HIV) continues to affect millions of people worldwide. Preventive measures have done little to slow the transmission of the virus. Discovery of an effective vaccine to prevent HIV could have a tremendous impact on this global pandemic. However, the complex interactions between HIV and the host immune system have limited the progress in vaccine development. Traditional vaccination strategies have shown little promise. Currently, subunit vaccines, DNA vaccines, recombinant vector vaccines, and prime-boost strategies are being evaluated in clinical trials. Although many breakthroughs have been made in HIV vaccine research, only three candidate HIV vaccines have been studied in phase III clinical trials. The current strategies being investigated in the development of preventive HIV vaccines are reviewed.


Purinergic signalling at the plasma membrane: a multipurpose and multidirectional mode to deal with amyotrophic lateral sclerosis and multiple sclerosis.
ATP is a widespread and multipurpose signalling molecule copiously released in the extracellular environment of the whole nervous system upon cell activation, stress, or damage. Extracellular ATP is also a multidirectional information molecule, given the concurrent presence at the plasma membrane of various targets for ATP. These include ectonucleotidases (metabolizing ATP down to adenosine), ATP/adenosine transporters, P2 receptors for purine/pyrimidine nucleotides (ligand-gated ion channels P2X receptors and G-protein-coupled P2Y receptors), in addition to metabotropic P1 receptors for nucleosides. All these targets rarely operate as single units, rather they associate with each other at the plasma membrane as multi-protein complexes. Altogether, they control the duration, magnitude and/or direction of the signals triggered and propagated by purine/pyrimidine ligands, and the impact that each single ligand has on a variety of short- and long-term functions. A strict control system allows assorted, even divergent, biological outcomes. Among these, we enumerate cell-to-cell communication, tropic, trophic, but also noxious actions causing the insurgence/progression of pathological conditions. Here, we show that purinergic signalling in the nervous system can be instrumental for instance to neurodegenerative and neuroinflammatory diseases such as amyotrophic lateral sclerosis and multiple sclerosis.


Contribution of residential exposures to asthma in us children and adolescents.
Residential exposures are recognized risk factors for asthma, but the relative contribution of specific indoor allergens and their overall contribution to asthma among older children and adolescents in the United States are unknown. To estimate the relative contributions, population-attributable risks, and costs of residential risk factors for doctor-diagnosed asthma. Design. Nationally representative, cross-sectional survey conducted from 1988 to 1994. A total of 5384 children who were 6 to 16 years old and participated in the National Health and Nutrition Examination Survey III, a survey of the health and nutritional status of children and adults in the United States. Doctor-diagnosed asthma, as reported by the parent. Five hundred three of 5384 children and adolescents (11.4%) had doctor-diagnosed asthma. After adjusting for age, gender, race, urban status, region of country, educational attainment of the head of household, and poverty, predictors of doctor-diagnosed asthma included a history of allergy to a pet (odds ratio [OR: 2.4; 95% confidence interval [CI]: 1.7, 3.3), presence of a pet in the household (OR: 1.5; 95% CI: 1.1, 2.1), and immediate hypersensitivity to dust mite (OR: 1.5; 95% CI: 1.05, 2.0), Alternaria (OR: 1.9; 95% CI: 1.3, 2.8), and cockroach allergens (OR: 1.4; CI: 1.04, 1.9). Family history of atopy (OR: 1.7; 95% CI: 1.1, 2.7) and diagnosis of allergic rhinitis (OR: 2.1; CI: 1.1, 3.7) were also predictors for asthma. The population-attributable risk of having 1 or more residential exposures associated with doctor-diagnosed asthma was 44.4% (95% CI: 29-60), or an estimated 2 million excess cases. The attributable cost of asthma resulting from residential exposures was $405 million (95% CI: $264-$547 million) annually. The elimination of identified residential exposures, if causally associated with asthma, would result in a 44% decline in doctor-diagnosed asthma among older children and adolescents in the United States.


Neuroprotective activity of HU-211, a novel NMDA antagonist, in global ischemia in gerbils.
HU-211, a nonpsychotropic cannabinoid and a noncompetitive NMDA antagonist, was tested in a global ischemia model in the Mongolian gerbil. Male Mongolian gerbils underwent a 10-min bilateral common carotid artery occlusion. HU-211, administered i.v. at 4 mg/kg, 30 min postischemia, induced statistically significant neuroprotection of the CA1 subfield of the hippocampus. A dose-response study demonstrated an inverted U curve in which the 4 mg/kg dose induced the best neuroprotection in the CA1 subfield of the hippocampus (p < 0.05 ANOVA followed by Duncan's post-hoc test). The therapeutic window was then investigated, and in another study, HU-211 4 mg/kg were administered i.v. at 30, 60, 120, and 180 min postinsult. A statistically significant neuroprotection was detected at 30 and 60 min administration postinsult.


Plasma big endothelin-1 levels at admission and future cardiovascular outcomes: A cohort study in patients with stable coronary artery disease.
Big endothelin-1 (ET-1) has been proposed as a novel prognostic indicator of acute coronary syndrome, while its predicting role of cardiovascular outcomes in patients with stable coronary artery disease (CAD) is unclear. A total of 3154 consecutive patients with stable CAD were enrolled and followed up for 24months. The outcomes included all-cause death, non-fatal myocardial infarction, stroke and unplanned revascularization (percutaneous coronary intervention and coronary artery bypass grafting). Baseline big ET-1 was measured using sandwich enzyme immunoassay method. Cox proportional hazard regression analysis and Kaplan-Meier analysis were used to evaluate the prognostic value of big ET-1 on cardiovascular outcomes. One hundred and eighty-nine (5.99%) events occurred during follow-up. Patients were divided into two groups: events group (n=189) and non-events group (n=2965). The results indicated that the events group had higher levels of big ET-1 compared to non-events group. Multivariable Cox proportional hazard regression analysis showed that big ET-1 was positively and statistically correlated with clinical outcomes (Hazard Ratio: 1.656, 95% confidence interval: 1.099-2.496, p=0.016). Additionally, the Kaplan-Meier analysis revealed that patients with higher big ET-1 presented lower event-free survival (p=0.016). The present study firstly suggests that big ET-1 is an independent risk marker of cardiovascular outcomes in patients with stable CAD. And more studies are needed to confirm our findings.


Antigen discovery in chronic human inflammatory central nervous system disease: panning phage-displayed antigen libraries identifies the targets of central nervous system-derived IgG in subacute sclerosing panencephalitis.
The presence of increased IgG in the brains of humans with infectious and inflammatory CNS diseases of unknown etiology such as multiple sclerosis may be a clue to the cause of disease. For example, the intrathecally synthesized oligoclonal bands in diseases such as subacute sclerosing panencephalitis (SSPE) or cryptococcal meningitis have been shown to represent Ab directed against the causative agents, measles virus (MV), or Cryptococcus neoformans, respectively. Using SSPE as a model system, we developed a strategy to identify the antigenic targets of the intrathecal disease-relevant IgG in chronic human inflammatory and demyelinating diseases of the CNS. Libraries of cDNA Ags were displayed on the surface of T7Select bacteriophage and biopanned on IgG extracted from the brain of an SSPE patient, or on a monospecific recombinant Fab identified from SSPE brain. After three or six rounds of biopanning on either Ab, positive phage-displayed Ags reacting with IgG were enriched to 35-77% of all panned clones. Sequence analysis of the positive clones identified fragments of the nucleocapsid protein of MV, the cause of SSPE. The sensitivity of the system was determined by diluting the positive clones from this SSPE phage-displayed library at a ratio of 10(-6) into another phage-displayed library that did not contain any detectable MV Ags; after six rounds of panning, the positive clones comprised 34% of all phage and were also shown to be MV nucleocapsid specific. This strategy will be useful to identify potentially rare Ags in diseases of unknown cause.


Estimates of the incidence and prevalence of hepatocellular carcinoma in Italy in 2002 and projections for the years 2007 and 2012.
Data on liver cancer incidence and prevalence in Italy are not available on a national and regional level. We provided estimates of the number of incident and prevalent cases for hepatocellular carcinoma in Italy overall and in various regions in 2002 and gave projections for the years 2007 and 2012. We obtained annual numbers of incident cases of hepatocellular carcinoma by combining mortality data provided by the World Health Organization and information on survival for liver cancer, and subsequently derived five-year prevalence for hepatocellular carcinoma by combining incidence with information on survival. In 2002, there were about 5800 incident cases and 4300 prevalent cases of hepatocellular carcinoma in Italy. The most reliable estimate of hepatocellular carcinoma incident cases in Italy in 2007 is between 5500 and 6000, and this figure is likely to decline to 5000-5500 in 2012. The best estimate of prevalence is about 4000 cases in 2007, which is likely to decline to 3700 in 2012. Incidence and prevalence of hepatocellular carcinoma are likely to remain approximately stable between 2002 and 2007 and slightly decrease in the subsequent quinquennia. These projections are, however, subject to large uncertainties because of the problems in diagnosis and death certification for this neoplasm, particularly for the elderly.


Acute Stroke Patients With Mild-to-Moderate Pre-existing Disability Should Be Considered for Thrombolysis Treatment.
Thrombolytic therapy in patients with pre-existing disability presenting with acute ischemic stroke (AIS) is controversial because of concerns regarding poor outcomes and futility of treatment. We hypothesized that a similar proportion of patients with and without pre-existing disability would return to their premorbid functional status following thrombolysis. This was a retrospective study at a single high-volume academic primary stroke center. All patients with AIS treated with intravenous alteplase between January 2005 and July 2016 were included. Premorbid functional status was assessed using modified Rankin scale (mRS) and dichotomized as independent premorbid (mRS 0-1) or disabled premorbid (mRS 2-4) groups for comparison. Functional outcome was assessed by mRS at 90 days and compared between groups. Six hundred eighty patients independent premorbid (mean age 71.8 ± 13.1 years, 57.9% male) and 140 disabled premorbid (mean age 82.1 ± 8.7 years, 40.7% male) were included. Patients with pre-existing disability were older and had more vascular risk factors and more severe stroke on presentation (P < 0.05). A greater proportion of patients in the disabled premorbid group were dead at 90 days (35.7% versus 12.8%, P < 0.05). At 90 days, among patients with premorbid mRS 0, 1, 2, 3, and 4: 25%, 38%, 32%, 30%, and 25% of them returned to their respective premorbid mRS status. Irrespective of premorbid functional level, approximately one fourth to one third of thrombolyzed patients had returned to their premorbid functional levels at 90 days. Thrombolytic treatment should be considered in patients with mild-to-moderate pre-existing disability, taking into account the value placed on the chance of a return to premorbid functional status.


Inhibition of photosystem II photochemistry by Cr is caused by the alteration of both D1 protein and oxygen evolving complex.
The effect of chromium (Cr) on photosystem II (PSII) electron transport and the change of proteins content within PSII complex were investigated. When Lemna gibba was exposed to Cr during 96 h, growth inhibition was found to be associated with an alteration of the PSII electron transport at both PSII oxidizing and reducing sides. Investigation of fluorescence yields at transients K, J, I, and P suggested for Cr inhibitory effect to be located at the oxygen-evolving complex and Q(A) reduction. Those Cr-inhibitory effects were related to the change of the turnover of PSII D1 protein and the alteration of 24 and 33 kDa proteins of the oxygen-evolving complex. The inhibition of the PSII electron transport and the formation of reactive oxygen species induced by Cr were highly correlated with the decrease in the content of D1 protein and the amount of 24 and 33 kDa proteins. Therefore, functional alteration of PSII activity by Cr was closely related with the structural change within PSII complex.


Impact of diet-related cancer prevention messages written with cognitive and affective arguments on message characteristics, stage of change, and self-efficacy.
To determine if participants reading messages matched to a preferred style of message argument respond more favorably than participants reading unmatched messages. Randomized trial using telephone and in-person surveys and cognitive response interviews. University campus. Of 125 initially interested, a convenience sample of 100 university employees completed the study (female: 88%, white: 94%, mean age: 43.7). Participants read 2 print messages written with cognitive (COG) (fact based) or affective (AFF) (story based) arguments. 7-point Likert scale ratings of message appeal, understandability, persuasiveness, and relevance according to classification into 1 of 4 message groups: COG-AFF (mismatched to affective), AFF-COG (mismatched to cognitive), COG-COG (matched cognitive), and AFF-AFF (matched affective). 1-way analysis of variance (P < or = .05) and systematic review of qualitative interviews. The COG-AFF group consistently gave the lowest ratings to the affective messages and the AFF-COG group generally gave high scores compared with other message groups. Participants also expressed a desire for more factual information. A combination of cognitive and affective arguments may be appealing to subjects with an affective preference but disliked by individuals who prefer only a fact-based approach. Argument format may be an important message design consideration.


The T-cell repertoire is heavily influenced by tolerance to polymorphic self-antigens.
T cells with V beta 3+ alpha beta receptors are deleted by self-tolerance in mice with particular major histocompatibility complex/self-antigen combinations. This also occurs for other V beta elements. Polymorphism in the major histocompatibility complex and/or the self-antigens that cause massive deletion of T cells using particular V beta elements may be maintained by the need to balance the advantage of a diverse T-cell repertoire against the potential involvement of those elements in autoimmune disease.


Pulmonary infections mimicking cancer: a retrospective, three-year review.
Pulmonary infections can mimic or occasionally co-exist with pulmonary neoplasms. In order to determine the frequency and nature of these infections, we conducted a retrospective analysis, covering a 3-year period, of patients who were referred to our center with presumed lung cancer but turned out to have pulmonary infection instead. The overwhelming majority of patients (93.3%) referred to "rule out" lung cancer were documented as having a neoplastic process, and only 1.3% had an infection. Fungal infections (histoplasmosis, cryptococcosis, coccidiomycosis) accounted for 46%, mycobacteria for 27%, bacteria for 22%, and parasitic lesions (dirofilariasis) for 5% of these infections. The most common clinical manifestations were cough and chest pain, and the most common radiographic finding was a solitary pulmonary nodule. There were no specific clinical or radiographic features predictive of either infection or neoplastic disease. All patients responded to specific anti-infective therapy with or without surgical excision. Our data indicate that pulmonary infections mimic neoplasms very infrequently. However, establishing a specific diagnosis is critical, since the management and outcome of these two processes are entirely different.


Chronic kidney disease 5 on hemodialysis in Nepal Medical College Teaching Hospital.
Chronic Kidney Disease (CKD) 5 is defined when glomerular filtration rate (GFR) is <15.0 ml/min/1.73m2. Though nephrology service was started in Nepal as early as in 1970, we do not have data regarding CKD 5 patients till date. So this study is being undertaken to know the epidemiological profile and etiology of CKD 5 patients attending hemodialysis (HD) unit of Nepal Medical College Teaching Hospital. This is a prospective study which was carried out in HD unit over a period of one year. CKD 5 patients having GFR of <15 ml/min/1.73m2 under HD were included in the study. Among 100 patients included in the study 57 were male and mean age of the study population was 46.9+/-17.9 years. Most common cause of CKD 5 in the study was hypertension (54.0%); other causes included diabetic nephropathy (18.0%), idiopathic (13.0%) and glomerulonephritis (6.0%). Fifty percent of patients were from outside Kathmandu Valley. Around 20.0% of the study population is on regular follow up while 45.0% were lost to follow up. Twenty percent of the patient underwent transplantation and 15.0% of the study population died. Majority of patients were anemic (85.0%). Correction of anemia was done with blood transfusion in 88.0% and only 12.0% received erythropoietin. Hypertension was the leading cause of CKD 5; majority of patients (45.0%) discontinued hemodialysis most probably due to economical constrain; blood transfusion was the main modality of treatment of anemia.


Memory associations between negative emotions and alcohol on the lexical decision task predict alcohol use in women.
Implicit alcohol expectancies, or beliefs about alcohol which exist in the form of automatic memory associations, are thought to uniquely affect drinking behavior. Research also has indicated that there may be a distinctive relationship between negative reinforcement and alcohol use in women. However, the most common measures used to examine implicit alcohol cognitions may be insufficient to examine associations involving negative reinforcement. The current study utilized the Lexical Decision Task (LDT) to examine the relationship between implicit alcohol cognitions and reported drinking in a sample of college women. Seventy-eight female participants completed a LDT including alcohol- and emotion-words, questionnaire measures of explicit alcohol expectancies, and a measure of drinking behavior at baseline and after two months. Strong associations between negative emotion-words and alcohol-words (as measured by the LDT) were found to predict drinking at follow up, and to account for unique variance in drinking beyond the contribution of explicit measures. In addition, women who reported heavier drinking in response to social conflict on an explicit measure showed stronger priming of alcohol words by negative emotion words, thus implying that the LDT may tap into implicit cognitions related to alcohol use as a method of coping. These findings suggest that the LDT is sensitive to negative-reinforcement associations in a way that other measures are not.


Excellent thermoelectric performance induced by interface effect in MoS2/MoSe2 van der Waals heterostructure.
Herein, thermoelectric properties of MoS2/MoSe2 lateral and van der Waals heterostructure are investigated by using density functional theory calculations and non-equilibrium Green's function method. Compared with pure MoS2, the thermoelectric performance of MoS2/MoSe2 lateral heterostructure is significantly improved due to the sharply decreased thermal conductance and slightly reduced power factor. Moreover, the thermoelectric performance can be further improved by constructing MoS2/MoSe2 van der Waals heterostructure. The room temperature ZT can reach 3.5, which is about 3 and 6 times greater than MoS2/MoSe2 lateral heterostructure and pure MoS2, respectively. This is because the strongly local electron and phonon states result in an ultralow thermal conductance in MoS2/MoSe2 van der Waals heterostructure. Furthermore, we also find that the thermoelectric performance of MoS2/MoSe2 van der Waals heterostructure is insensitive to contact areas due to the competing influence of PF and total thermal conductance. The current study presents an effective strategy to improve the thermoelectric performance of 2D heterostructures, which can be extended to a variety of materials for different applications.


Determination of antioxidant capacities, α-dicarbonyls, and phenolic phytochemicals in Florida varietal honeys using HPLC-DAD-ESI-MS(n.).
Honeys contain phenolic compounds and α-dicarbonyls with antioxidant and antimicrobial capacities, respectively. The type and concentration of these compounds vary depending on the floral source and geographical location where the honey is produced. Seventeen varietal honeys, including 12 monofloral and 5 multifloral honeys, were sampled from different regions of Florida. The monofloral honeys included those from citrus, tupelo, palmetto, and gallberry. These honeys were evaluated for their antioxidant capacity, total phenolic content, and free radical scavenging capacity and compared with three New Zealand Manuka honeys. Phenolic phytochemicals and α-dicarbonyls were identified and quantified using HPLC-DAD-MS(n). Several honey varieties from gallberry, Manuka, and multifloral displayed a total phenolic content >1000 μg GAE/g. A citrus honey had the lowest total phenolic content of 286 μg GAE/g. The oxygen radical absorbance capacity of the honeys ranged from 1.48 to 18.2 μmol TE/g. All honeys contained 3-deoxyglucosone at a higher concentration than methylglyoxal or glyoxal. Manuka honeys had higher concentrations of methylglyoxal than other varieties. Plant hormones 2-cis,4-trans-abscisic acid and 2-trans,4-trans-abscisic acid were the most abundant phytochemicals in all honeys. Coumaric acid, rutin, chrysin, pinocembrin, quercetin, luteolin, and kaempferol were also found in samples but at lower concentrations.


Memory T lymphocytes.
Immunological memory protects organisms from recurrent challenge by pathogens. The persistence of a heightened reactive state initiated by antigenic challenge is mediated by long-lived memory lymphocytes. The survival of memory T cells is thought to require stimulation through the T cell receptor (TCR), sometimes by persistent antigen. However, memory T cells can survive in the absence of antigen, in which case TCR stimulation provided by cell surface self-peptide/ major histocompatibility complex (MHC) molecules and cytokines are required to sustain memory T cells. Recent work using mouse models has provided insights into the origin of memory T cells. Understanding the mechanisms that underlie the differentiation and persistence of memory T cells may improve the effectiveness of vaccines through the induction of T cell memory.


Inhibition of GSK-3beta Signaling Pathway Rescues Ketamine-Induced Neurotoxicity in Neural Stem Cell-Derived Neurons.
Clinical application of anesthetic reagent, ketamine (Keta), may induce irreversible neurotoxicity in central nervous system. In this work, we utilized an in vitro model of neural stem cells-derived neurons (nSCNs) to evaluate the role of GSK-3 signaling pathway in Keta-induced neurotoxicity. Embryonic mouse-brain neural stem cells were differentiated into neurons in vitro. Keta (50 μM)-induced neurotoxicity in cultured nSCNs was monitored by apoptosis, immunohistochemical and western blot assays, respectively. GSK-3 signaling pathways, including GSK-3α and GSK-3β, were inhibited by siRNA in the culture. The subsequent effects of GSK-3α or GSK-3β downregulation on Keta-induced neurotoxicity, including apoptosis and neurite loss, were then evaluated in nSCNs. Finally, caspase and Akt/ERK signal pathways were further examined by western blot to evaluate the regulatory effect of GSK-3 signaling pathways on Keta-induced neural injury. Keta (50 μM) caused markedly nSCN apoptosis and neurite degeneration in vitro. Keta decreased GSK-3β phosphorylation, but had no effect on GSK-3α phosphorylation. SiRNA-induced GSK-3β downregulation rescued Keta-induced neurotoxicity in nSCNs by reducing neuronal apoptosis and preventing neurite degeneration. On the other hand, GSK-3α downregulation had no effect on Keta-induced neurotoxicity. Western blot showed that, in Keta-injured nSCNs, GSK-3β downregulation reduced Caspase-1/3 proteins, but left phosphorylated Akt/ERK unchanged. GSK-3β, not GSK-3α, was specifically involved in the process of Keta-induced neurotoxicity in nSCNs. Inhibiting GSK-3β may be an effective approach to counter toxic effect of ketamine on central neurons in clinical and experimental applications.


[Experimental study of human recombinant insulin].
The experimental study of recombinant human insulin revealed its high specific activity. The kinetics of the hypoglycemic effect of various dosage forms of the insulin developed at the National Research Centre of Antibiotics and the dosage forms manufactured by Eli Lilly was similar. The pharmacological investigation of the dosage forms showed that they had no side effects on the vitally important organs and systems. It was concluded that the dosage forms of the gene engineered human insulin developed at the National Research Centre of Antibiotics did not differ by their characteristics from the analogous dosage forms manufactured in other countries.


[Design of the general population study NEMESIS-2: Netherlands Mental Health Survey and Incidence Study-2].
The longitudinal epidemiological population study NEMESIS-2 (Netherlands Mental Health Survey and Incidence Study-2) replicates the first study conducted from 1996 to 1999, and expands it by adding new subjects such as impulse-control disorders. To describe the aims and design of nemesis-2, particularly of its first round of measurements, to provide up-to-date figures on prevalence, incidence, course and consequences of mental disorders and associated factors, and to study trends in the mental health of the population aged 18-64 years and the use these people make of psychiatric services. Face-to-face interviews were conducted (November 2007-July 2009) by means of the Composite International Diagnostic Interview 3.0. The response was 65.1% (n = 6646). Respondents were reasonably representative for the population, but young persons were somewhat underrepresented. Two follow-up rounds of measurements are planned with three-year intervals between the rounds. The second round of measurements began in November 2010. A qualitatively good dataset was built up. This will allow several mental health topics to be studied in the future.


Diuretic effect of ITA 529.
The diuretic and saluretic activity of ITA 529 (Ethyl-beta-[(5-tert-butyl-3-chloro-2-hydroxy)benzylamino]crotonate++ +) in rat, rabbit and monkey is described in this study. In rat, the diuretic ED50 of ITA 529 was 1.23 mg/kg p.o. and its ED100 1.69 mg/kg p.o. The diuretic ED50 of furosemide was 18.48 mg/kg p.o. and its ED100 22.38 mg/kg p.o. Their effect lasted approximately 3 hours. In monkey, the diuretic ED50 of ITA 529 was 2.29 mg/kg p.o. and its ED100 6.54 mg/kg p.o. while for furosemide its ED50 was 2.44 mg/kg p.o. and its ED100 5.72 mg/kg p.o. In rabbit the ED50 of ITA 529 was 1.83 mg/kg p.o. and its ED100 3.37 mg/kg p.o. For furosemide, its ED50 was 2.25 mg/kg p.o. and its ED100 7.13 mg/kg p.o. The natriuretic activity of ITA 529 was reduced by indomethacin.


CD27 is acquired by primed B cells at the centroblast stage and promotes germinal center formation.
Studies on human B cells have featured CD27 as a marker and mediator of the B cell response. We have studied CD27 expression and function on B cells in the mouse. We find that B cells acquire CD27 at the centroblast stage and lose it progressively upon further differentiation. It is not a marker for somatically mutated B cells and is present at very low frequency on memory B cells. Enrichment of CD27 among centroblasts and the presence of its ligand CD70 on occasional T and B cells in or near germinal centers (GCs) suggested a role for CD27/CD70 interactions in clonal B cell expansion. Accordingly, GC formation in response to influenza virus infection was delayed in CD27 knockout mice. CD27 deficiency did not affect somatic hypermutation or serum levels of virus-specific IgM, IgG, and IgA attained in primary and recall responses. Adoptive transfer of T and B cells into CD27/CD28(-/-) mice revealed that CD27 promotes GC formation and consequent IgG production by two distinct mechanisms. Stimulation of CD27 on B cells by CD28(+) Th cells accelerates GC formation, most likely by promoting centroblast expansion. In addition, CD27 on T cells can partially substitute for CD28 in supporting GC formation.


Fixed implant-supported prostheses in elderly patients: a 5-year retrospective comparison between partially and completely edentulous patients aged 80 years or older at implant surgery.
Knowledge on implant treatment in the partially edentulous patient is low for elderly patients aged 80 years or older at inclusion. The objective of this study was to report and compare the clinical and radiological performance of implant treatment in edentulous and partially edentulous elderly patients during 5 years in function. Altogether, 192 edentulous (control) and 72 partially edentulous (study) patients, consecutively treated and provided with 1,091 and 265 Brånemark implants, respectively, were included during a period between January 1986 and December 2003, and followed-up for 5 years. Clinical information was retrospectively retrieved from patient files and intraoral radiographs were analyzed for examinations at prosthesis placement and after 1 and 5 years in function. Altogether, 92 (48%) control and 24 (33%) study patients were lost to follow-up during the 5-year period. In total, 13 (4.9%) and 26 (2.4%) implants were in the study and control groups, respectively, were lost during follow-up, resulting in a comparable 5-year implant cumulative survival rate ranging from 93.9% to 99.3% for upper and lower jaws for study and control groups, respectively. Comparable mean marginal bone loss during 5 years, ranging from 0.4 mm to 0.6 mm, was also observed in the groups. The most common complications for patients in both study and control group were soft tissue inflammation (mucositis). Patients included in the first years of the inclusion (1986-1991) period showed comparable results as patient included at the last part of the inclusion period (1998-2003). Implant treatment in the partially edentulous elderly patients showed comparable clinical and radiographic results as elderly patients treated in the edentulous jaw.


Inhibition of highly pathogenic porcine reproductive and respiratory syndrome virus replication by recombinant pseudorabies virus-mediated RNA interference in piglets.
Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is a variant of porcine reproductive and respiratory syndrome virus (PRRSV) which, in recent years, has caused heavy economic losses to swine-producing areas. Although current vaccines are somewhat prophylactic, they provide only limited protection. Furthermore, there are currently no effective anti-HP-PRRSV drugs. Consequently, it is necessary to develop novel antiviral strategies. In the present study, three recombinant pseudorabies viruses (PRV) expressing siRNAs against the ORF7 of HP-PRRSV strain HN1 (PRV gG-/siRNAN1, PRV gG-/siRNAN2, and PRV gG-/siRNAN3) were evaluated for the inhibition of HP-PRRSV replication. The results indicated that recombinant PRV-mediated siRNA could significantly decrease the replication of traditional PRRSV strain H1 at mRNA and protein levels in Marc-145 cells. Moreover, one recombinant PRV (PRV gG-/siRNAN2) was found to be inhibit the multiplication of HP-PRRSV strain HN1 effectively in Marc-145 cells at both the protein and ORF7 mRNA level. Twenty 21-day-old healthy weaned piglets were divided into four groups of five piglets each. Groups 1 and 2 were injected i.m. with PRV gG-/siRNAN2 and PRV gG-/siRNANeg individually. The piglets in group 3 were challenged with the HP-PRRSV control. After 24h, the piglets in groups 1-3 were challenged i.m. with HP-PRRSV strain HN1, while those in group 4 were i.m. administered with PBS as a negative control. The results showed that HP-PRRSV in serum and lung samples from piglets was effectively inhibited by PRV gG-/siRNAN2. The clinical signs and gross lesions of piglets inoculated with PRV gG-/siRNAN2 were significantly less invasive than those of the PRV gG-/siRNANeg group and HP-PRRSV control group. These results showed that siRNAs mediated by recombinant PRV could effectively suppress HP-PRRSV replication in vitro as well as in vivo. RNAi mediated by recombinant PRV presents a potential novel method to prevent HP-PRRSV infections in swine. However, the protective efficiency of PRV gG-/siRNAN2 should be assessed in a larger number of piglets in future studies.


Andrographis paniculata Diterpenoids Protect against Radiation-Induced Transformation in BALB/3T3 Cells.
One of the most concerning side effects of exposure to radiation are the carcinogenic risks. To reduce the negative effects of radiation, both cytoprotective and radioprotective agents have been developed. However, little is known regarding their potential for suppressing carcinogenesis. Andrographis paniculata , a plant, with multiple medicinal uses that is commonly used in traditional medicine, has three major constituents known to have cellular antioxidant activity: andrographolide (AP1); 14-deoxy-11,12-didehydroandrographolide (AP3); and neoandrographolide (AP4). In our study, we tested these elements for their radioprotective properties as well as their anti-neoplastic effects on transformation using the BALB/3T3 cell model. All three compounds were able to reduce radiation-induced DNA damage. However, AP4 appeared to have superior radioprotective properties compared to the other two compounds, presumably by protecting mitochondrial function. The compound was able to suppress radiation-induced cellular transformation through inhibition of STAT3. Treatment with AP4 also reduced expressions of MMP-2 and MMP-9. These results suggest that AP4 could be further studied and developed into an anti-transformation/carcinogenic drug as well as a radioprotective agent.


Vaccination and risk groups: how can we really protect the weakest?
Subjects who for their clinical conditions, age, occupational activities or living situations, are at increased risk of acquiring preventable infectious diseases or suffering from their complications, are the object of periodical attempts of identification and offer of vaccination. Several examples can be drawn from the past and from more recent experiences showing that targeted vaccination strategies usually fail to reach most of these subjects. As a matter of fact, obtaining a very high vaccination coverage in risk groups implies a complex integration of responsibilities in identifying, contacting, communicating with and immunizing many different categories of subjects. On the contrary, routine vaccination strategies of one or more cohorts of subjects have always shown the ability (if well implemented) to protect the weakest individuals in the community, due to the establishment of such a community protection as to get a remarkable positive impact even on those that are not immunized. It is ethically unsustainable that universal immunization strategies for diseases with remarkable impact and severity are delayed until an adequate coverage has been reached in subjects at risk, because this would paradoxically mean a serious damage just for those people that are the theoretical object of protection efforts through targeted vaccination strategies.


[Disease-related changes in work absenteeism of adolescents from 1967 to 1987].
The negative development of sickness figures up to 1976/77 as well as the subsequent change of this trend in adolescents are analysed with regard to specific diagnoses. Both, the positive trend change and remaining problems are presented.


Molecular and cellular mechanisms of porphyrin photosensitization.
Mechanisms of porphyrin-sensitized photochemistry involving biomolecular substrates have been studied in a diverse array of in vitro and in vivo experimental protocols. Porphyrin-sensitized, singlet oxygen-mediated photooxidative damage has been implicated in peroxidation of cell membrane lipids; cross-linking of cell membrane and intracellular proteins; inhibition of cell membrane associated, cytosolic, mitochondrial and microsomal enzymes; disruption of intracellular organelles with release of inflammatory mediators and hydrolases; damage to DNA with retarded protein synthesis and delay in cell cycle; and activation of complement-generated inflammatory events leading to cell injury or death.


Expression of small heat shock-related protein 20 (HSP20) in rat myometrium is markedly decreased during late pregnancy and labour.
The underlying mechanisms regulating uterine contractions during labour are still poorly understood. Heat shock protein 20 (HSP20) is known to be present at high levels in smooth muscle and implicated in muscle relaxation, but HSP20 expression in the myometrium is completely undetermined. Since HSP20 has been implicated in smooth muscle relaxation, we hypothesized that HSP20 would be highly expressed in the rat myometrium during early and mid-pregnancy when the myometrium is relatively quiescent. Northern blot analysis particularly demonstrated that HSP20 mRNA detection was significantly decreased from day (d) 22 of pregnancy to 1-day post-partum (PP) compared with d6 (P < 0.05). HSP20 mRNA detection was also significantly decreased from d22 to d23 of gestation compared with non-pregnant (NP) samples. Immunoblot analysis showed that detection of HSP20 was significantly decreased at d23 compared with d12 and d15 (P < 0.05). HSP20 detection also significantly decreased at PP compared with d15 (P < 0.05). Immunofluorescence analysis demonstrated that after d15, plasma membrane-associated localization of HSP20 decreased markedly in both circular and longitudinal muscle layers. In addition, HSP20 was detectable near cell membranes at much higher levels in the longitudinal muscle layer of progesterone-treated pregnant rats (delayed labour) at all gestational time points examined, compared with controls. Our results demonstrate that HSP20 mRNA and protein are highly expressed during early and mid-pregnancy and then the expression markedly decreases during late pregnancy and labour. The observed patterns of HSP20 expression are consistent with a potential role for HSP20 in facilitating myometrium quiescence during early and mid-pregnancy.


Efficient delivery of sticky siRNA and potent gene silencing in a prostate cancer model using a generation 5 triethanolamine-core PAMAM dendrimer.
Successful achievement of RNA interference in therapeutic applications requires safe and efficient vectors for siRNA delivery. In the present study, we demonstrate that a triethanolamine (TEA)-core PAMAM dendrimer of generation 5 (G(5)) is able to deliver sticky siRNAs bearing complementary A(n)/T(n) 3'-overhangs effectively to a prostate cancer model in vitro and in vivo and produce potent gene silencing of the heat shock protein 27, leading to a notable anticancer effect. The complementary A(n)/T(n) (n = 5 or 7) overhangs characteristic of these sticky siRNA molecules help the siRNA molecules self-assemble into "gene-like" longer double-stranded RNAs thus endowing a low generation dendrimer such as G(5) with greater delivery capacity. In addition, the A(n)/T(n) (n = 5 or 7) overhangs act as protruding molecular arms that allow the siRNA molecule to enwrap the dendrimer and promote a better interaction and stronger binding, ultimately contributing toward the improved delivery activity of G(5). Consequently, the low generation dendrimer G(5) in combination with sticky siRNA therapeutics may constitute a promising gene silencing-based approach for combating castration-resistant prostate tumors or other cancers and diseases, for which no effective treatment currently exists.


Iron polypyridyl catalysts assembled on metal oxide semiconductors for photocatalytic hydrogen generation.
A series of Fe(iii) complexes was recently reported that are active for photocatalytic hydrogen generation when paired with fluorescein and triethylamine. Herein we report an Fe(iii) complex immobilized on TiO2 and SrTiO3 that is significantly more active than the homogeneous system, achieving up to 7800 turnovers in 31 hours.


The burden of traditional practices, ebino and tea-tea, on child health in Northern Uganda.
Traditional medical practices persist today in Northern Uganda; for example, the operations of ebino and tea-tea are frequently performed in childhood. Ebino, or "false teeth", refers to gingival swellings during the eruption of the primary canine teeth in infants, and consists of the extraction of deciduous canine tooth buds. Tea-tea consists of systematic cuts made on the chest wall when the child has difficulty in breathing. The objectives of this study are to describe the morbidity and mortality related to complications arising from the ebino and tea-tea procedures among children admitted to the paediatric ward of St. Mary's Hospital Lacor in 1999, and to estimate the prevalence of ebino and tea-tea among children aged 0-4 years attending, for any cause, the child welfare department (CWD) of the hospital. The prevalence survey consisted of the examination of 1,995 children attending CWD during a four-week period in 1999 to look for missing primary canine teeth (ebino), and for "therapeutic" cuts on the chest wall (tea-tea). In the difficult context of war and social disruption prevailing in Northern Uganda, sustainable methods of data collection and analysis should be utilised to support evidence-based decision-making.


Electron ionization mass spectrometry for sequence analysis of glycosphingolipid mixtures by fractional evaporation in the ion source. Mass spectrometric evidence for an eleven-sugar glycolipid.
This paper describes the use of electron ionization mass spectrometry for structural characterization of a mixture of glycosphingolipids from a single human kidney and presents mass spectrometric evidence for the presence of an eleven-sugar glycolipid. A large amount of structural information is obtained from minor glycolipid constituents having long sugar chains by a fractional evaporation in the ion source, achieved by steadily increasing the ion-source temperature.


Expression of the Streptomyces alboniger pur cluster in Streptomyces lividans is dependent on the bldA-encoded tRNALeu.
Streptomyces lividans 1326-9, a bldA+ strain, and its bldA39 mutant derivative J1725 were transformed with a cosmid containing the pur cluster, which determines the puromycin biosynthetic pathway from Streptomyces alboniger. bldA+ transformants produced puromycin in typical amounts, whereas bldA39 transformants did so at drastically decreased levels. Transformation of low producers with the wild-type bldA gene reverted this phenotype to normal production. These data, in addition to the presence of a TTA codon in the amino-terminal coding region of the pur10 and pur6 genes of the pur cluster, suggest that the puromycin biosynthetic pathway is translationally dependent on the bldA gene product, a tRNALeu.