Bacteriological indicators of anthropogenic impact prior to and during the recovery of water quality in an extremely polluted estuary, Golden Horn, Turkey.
Five years of monthly data of indicator bacteria from 1998 to 2002 were evaluated to find out the changes in water quality during the rehabilitation of the Golden Horn, an estuary severely polluted from industrial and domestic discharges since the 1950s. Surface fecal coliform was above 10(6) CFU/100 ml at the inner part in 1998. Following the achievement of healthy water circulation and control of most surface discharges, fecal coliform and fecal streptococci counts decreased below 10(3) CFU/100 ml in the summer of 2002. However, the decrease was interrupted by sudden shifts in rainy periods. Runoff, enhanced by domestic inputs during rainfall, has become the main factor influencing water quality in the estuary today. Increasing values of fecal coliform were observed during periods of low salinity, pH, dissolved oxygen and high ortho-phosphate, whilst decreasing values were detected during high salinity, pH and dissolved oxygen and low ortho-phosphate periods. Striking changes were observed within five years, promising that even an anoxic water body can turn into a recreational area with appropriate treatment.


Shed syndecan-1 translocates to the nucleus of cells delivering growth factors and inhibiting histone acetylation: a novel mechanism of tumor-host cross-talk.
The heparan sulfate proteoglycan syndecan-1 is proteolytically shed from the surface of multiple myeloma cells and is abundant in the bone marrow microenvironment where it promotes tumor growth, angiogenesis, and metastasis. In this study, we demonstrate for the first time that shed syndecan-1 present in the medium conditioned by tumor cells is taken up by bone marrow-derived stromal cells and transported to the nucleus. Translocation of shed syndecan-1 (sSDC1) to the nucleus was blocked by addition of exogenous heparin or heparan sulfate, pretreatment of conditioned medium with heparinase III, or growth of cells in sodium chlorate, indicating that sulfated heparan sulfate chains are required for nuclear translocation. Interestingly, cargo bound to sSDC1 heparan sulfate chains (i.e. hepatocyte growth factor) was transported to the nucleus along with sSDC1, and removal of heparan sulfate-bound cargo from sSDC1 abolished its translocation to the nucleus. Once in the nucleus, sSDC1 binds to the histone acetyltransferase enzyme p300, and histone acetyltransferase activity and histone acetylation are diminished. These findings reveal a novel function for shed syndecan-1 in mediating tumor-host cross-talk by shuttling growth factors to the nucleus and by altering histone acetylation in host cells. In addition, this work has broad implications beyond myeloma because shed syndecan-1 is present in high levels in many tumor types as well as in other disease states.


Peroral endoscopic full-thickness myotomy for the treatment of sigmoid-type achalasia: outcomes with a minimum follow-up of 12 months.
To explore the feasibility, safety, and efficacy of peroral endoscopic full-thickness myotomy (fPOEM) for the treatment of sigmoid-type achalasia. From August 2011 to June 2014, a total of 23 sigmoid-type achalasia patients received fPOEM at our hospital. Among these patients, 19 had sigmoid-type 1 achalasia and the other four had sigmoid-type 2 achalasia. Clinical data of general characteristics, procedure-related parameters and adverse events, symptom relief, and manometry outcomes before and during the periodic follow-up were retrospectively collected and analyzed. All the patients successfully received fPOEM, with a mean procedure time of 67.6 min; six patients received a conventional fPOEM whereas the other 17 received a modified fPOEM. During a median follow-up of 18 months, the median Eckardt score decreased obviously (pre-POEM vs. post-POEM, 7.0 vs. 1.0, P<0.05), the mean lower esophageal sphincter pressures and 4s integrated relaxation pressure decreased (pre-POEM vs. post-POEM, 34.78±4.51 vs. 11.50±2.56 mmHg and 29.52±3.67 vs. 10.61±1.54 mmHg, P<0.01), and the esophageal diameter decreased (pre-POEM vs. post-POEM, 58.2±11.6 vs. 37.5±7.3 mm, P<0.05). Overall treatment success was achieved in 95.6% of the patients (22/23), and morphological improvement was observed in 95% (19/20) of the patients. In 10 patients (43.5%) complications were encountered, including gas-related complications, mucosal perforation, and reflux esophagitis. There was no significant difference in terms of efficacy between conventional fPOEM and modified fPOEM, but modified fPOEM may reduce the occurrence of gas-related complications. fPOEM is feasible, safe, and effective for the treatment of sigmoid-type achalasia. A modified fPOEM may reduce the occurrence of gas-related complications. Yet, further experiences and long-term results are warranted.


The affective harm account (AHA) of moral judgment: Reconciling cognition and affect, dyadic morality and disgust, harm and purity.
Moral psychology has long debated whether moral judgment is rooted in harm versus affect. We reconcile this debate with the affective harm account (AHA) of moral judgment. The AHA understands harm as an intuitive perception (i.e., perceived harm), and divides "affect" into two: embodied visceral arousal (i.e., gut feelings) and stimulus-directed affective appraisals (e.g., ratings of disgustingness). The AHA was tested in a randomized, double-blind pharmacological experiment with healthy young adults judging the immorality, harmfulness, and disgustingness of everyday moral scenarios (e.g., lying) and unusual purity scenarios (e.g., sex with a corpse) after receiving either a placebo or the β-blocker propranolol (a drug that dampens visceral arousal). Results confirmed the three key hypotheses of the AHA. First, perceived harm and affective appraisals are neither competing nor independent but intertwined. Second, although both perceived harm and affective appraisals predict moral judgment, perceived harm is consistently relevant across all scenarios (in line with the theory of dyadic morality), whereas affective appraisals are especially relevant in unusual purity scenarios (in line with affect-as-information theory). Third, the "gut feelings" of visceral arousal are not as important to morality as often believed. Dampening visceral arousal (via propranolol) did not directly impact moral judgment, but instead changed the relative contribution of affective appraisals to moral judgment-and only in unusual purity scenarios. By embracing a constructionist view of the mind that blurs traditional dichotomies, the AHA reconciles historic harm-centric and current affect-centric theories, parsimoniously explaining judgment differences across various moral scenarios without requiring any "moral foundations." (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Ovine model for critical-size tibial segmental defects.
A segmental tibial defect model in a large animal can provide a basis for testing materials and techniques for use in nonunions and severe trauma. This study reports the rationale behind establishing such a model and its design and conclusions. After ethics approval of the study, aged ewes (older than 5 y; n = 12) were enrolled. A 5-cm mid diaphyseal osteoperiosteal defect was made in the left tibia and was stabilized by using an 8-mm stainless-steel cross-locked intramedullary nail. Sheep were euthanized at 12 wk after surgery and evaluated by using radiography, microCT, and soft-tissue histology techniques. Radiology confirmed a lack of hard tissue callus bridging across the defect. Volumetric analysis based on microCT showed bone growth across the 16.5 cm(3) defect of 1.82 ± 0.94 cm(3). Histologic sections of the bridging tissues revealed callus originating from both the periosteal and endosteal surfaces, with fibrous tissue completing the bridging in all instances. Immunohistochemistry was used to evaluate the quality of the healing response. Clinical, radiographic, and histologic union was not achieved by 12 wk. This model may be effective for the investigation of surgical techniques and healing adjuncts for nonunion cases, where severe traumatic injury has led to significant bone loss.


Synthesis of isostructural cage complexes of copper with cobalt and nickel for deposition of mixed ceramic oxide materials.
Heterobimetallic molecular precursors [Co2(acac)2mu-OH)2Cu4(dmae)4Cl4] (2) and [Ni2(acac)2(mu-OH)2Cu4(dmae)4Cl4] (3) [dmaeH = N,N-dimethylaminoethanol and acac = 2,4-pentanedionate] for the deposition of mixed oxide thin films were prepared by the interaction of tetrameric N,N-dimethylaminoethanolato copper(II) chloride, [Cu(dmae)Cl]4 (1) with M(acac)2.xH2O, [M = Co, Ni] in toluene. Both heterobimetallic cage complexes were characterized by melting point, elemental analysis, FT-IR spectroscopy, mass spectrometry, magnetometery, and single-crystal X-ray diffraction. Complexes 2 and 3 are isostructural and crystallize in the monoclinic space group P21/n. A TGA study shows that both complexes undergo controlled thermal decomposition at 450 degrees C to give mixed metal oxides. Solid-state infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDX), and X-ray powder diffraction (XRD) analysis were performed to analyze the chemical composition and surface morphology of the deposited oxide thin films. The results obtained indicate the formation of impurity-free crystalline mixed oxide films with particle sizes ranging from 0.55 to 2.0 microm.


Electrical stimulation of onlay bone grafts.
An animal model was developed to determine the ability of capacitively coupled electrical fields to enhance onlay bone graft survival in the craniofacial skeleton. Fifteen male New Zealand white rabbits were divided into control and stimulated groups. Blocks of iliac bone were transplanted as onlay grafts to the mandibular rami. In all animals a capacitor apparatus was attached externally over the right mandibular ramus; however, a 5-V peak-to-peak sinusoidal signal was applied only in the stimulated group. The experimental period was 6 weeks, with a total of 30 days of constant stimulation. Graft resorption in the stimulated animals was decreased a total of 24.8 percent (p less than 0.001). There appeared to be a trend toward decreased graft resorption caused by the apparatus alone, although this was not statistically significant. The electric field alone decreased resorption by 11.5 percent (p less than 0.05). No distinguishing features were demonstrated by fluorescent vital stains or routine histology.


To breathe or not to breathe? That is the question.
Our understanding of the role of the brain in respiratory rhythm generation and regulation began the early nineteenth century. Over the next 150 years the neuronal groups in the medulla oblongata and pons that were involved in eupnoea and in gasping were identified by techniques involving the lesioning of areas of the lower brainstem, several transections across the brainstem and focal electrical stimulation. An incomplete picture emerged that stressed the importance of the ventral medulla. Subsequent electrophysiological studies in in vivo, in situ and in vitro preparations have revealed the importance of restricted groups of neurones in this area, within the Bötzinger and pre-Bötzinger nuclei, that are the essential kernel for rhythm generation. The outputs to the spinal motoneurones responsible for the patterning of inspiratory and expiratory discharge are shaped by inputs from these neurones and others within the respiratory complex that determine the activity of respiratory bulbospinal neurones. It is clear that the developmental stage of the preparation is often critical for the pattern of respiratory activity that is generated and that these patterns have important physiological consequences. The models that are currently considered to explain rhythmogenesis are critically evaluated. The respiratory network is subject to regulation from peripheral and central chemoreceptors, amongst other afferent inputs, which act to ensure respiratory homeostasis. The roles of peripheral chemoreceptors as primarily O(2) sensors are considered, and the evolution of ideas surrounding their roles is described. New insights into the transduction mechanisms of chemoreception in the carotid body and chemosensitive areas of the ventral medullary surface, specifically in monitoring CO(2) levels, are reviewed. As new experimental tools, both genetic and cellular, are emerging, it can be expected that the detailed network architecture and synaptic interactions that pattern respiratory activity in relation to behavioural activity will be revealed over the next years.


The sphingomyelin synthase family: proteins, diseases, and inhibitors.
Sphingomyelin (SM) is among the most important biomolecules in eukaryotes and acts as both constructive components and signal carrier in physiological processes. SM is catalyzed by a membrane protein family, sphingomyelin synthases (SMSs), consisting of three members, SMS1, SMS2 and SMSr. SMSs modulate sphingomyelin and other sphingolipids levels, thereby regulating membrane mobility, ceramide-dependent apoptosis and DAG-dependent signaling pathways. SMSs was found associated with various diseases. Downregulation of SMS2 activity results in protective effects against obesity, atherosclerosis and diabetes and makes SMS2 inhibitors potential medicines. Structural guided specific drug design could be the next breakthrough, discriminating SMS2 from other homologs.


Patients and staff help choose designs.
A wide selection of Altro flooring and wallcovering products have been used in the award-winning Ferndene Children and Young People's Centre in Prudhoe, Northumberland, to create a healing environment that, according to the company, 'is visually stunning, as well as safe, hard-wearing, and hygienic'. HEJ reports.


A Quantitative and Qualitative Exploration of Photoaversion in Achromatopsia.
Photoaversion (PA) is a disabling and ubiquitous feature of achromatopsia (ACHM). We aimed to help define the characteristics of this important symptom, and present the first published assessment of its impact on patients' lives, as well as quantitative and qualitative PA assessments. Molecularly confirmed ACHM subjects were assessed for PA using four tasks: structured survey of patient experience, novel quantitative subjective measurement of PA, visual acuities in differing ambient lighting, and objective palpebral aperture-related PA testing. Photoaversion in ACHM was found to be the most significant symptom for a substantial proportion (38%) of patients. A novel subjective PA measurement technique was developed and demonstrated fidelity with more invasive paradigms without exposing often very photosensitive patients to brighter light intensities used elsewhere. An objective PA measurement was also refined for use in trials, indicating that higher light intensities than previously published are likely to be needed. Monocular testing, as required for trials, was also validated for the first time. This study offers new insights into PA in ACHM. It provides the first structured evidence of the great significance of this symptom to patients, suggesting that PA should be considered as an additional outcome measure in therapeutic trials. It also offers new insights into the characteristics of PA in ACHM, and describes both subjective and objective measures of PA that could be employed in clinical trials.


Phosphorylation analysis of G protein-coupled receptor by mass spectrometry: identification of a phosphorylation site in V2 vasopressin receptor.
Phosphorylation plays vital roles in the regulation and function of the V2 vasopressin receptor (V2R), a G protein-coupled receptor (GPCR) that is responsible for maintaining water homeostasis in the kidney. Through a combination of immunoaffinity purification, immobilized metal affinity chromatography, and nanoflow liquid chromatography tandem mass spectrometry, we identified a novel phosphorylation site (Ser(255)) in the third intracellular loop of human V2R. We showed that the third intracellular loop could be phosphorylated in vitro by protein kinase A, but not by Akt kinase, although sequence motif analysis predicated otherwise. The analytical procedures and methodologies described in this study should be generally applicable for identifying the endogenous phosphorylation sites in other GPCRs, overcoming the limitations of conventional approaches such as sequence motif analysis and site-directed mutagenesis.


Patient education among nurses: bringing evidence into clinical applicability in Iran.
The aim of this study was to present a comprehensive review of the literatures describing barriers and facilitators of patient education (PE) perceived by Iranian nurses in order to explain clinical applicability of patient education. Review of the literature was undertaken using the international databases including PubMed/Medline, Scopus, ScienceDirect, as well as Google Scholar. Also, Persian electronic databases such as Magiran, SID and IranMedex were searched. Electronic databases were searched up from conception to September 2014 using search terms: "patient education", " patients education", "patient teaching", "patient training", "nurse", " nurses", " nursing", " and "Iran". Only studies were included that were related to barriers and facilitators of PE among Iranian nurses. Twenty-seven studies were included. The main influential barriers were categorized into three major areas: 1) Nurse-related factors: nursing shortage 2) Administration-related factors: unsupportive organizational culture, and 3) Patient-related factors: low compliance. The most perceived facilitators were recognized as "increasing, selecting and training special nurses for providing PE" and "providing PE courses for nurses and appropriate facilities for PE". Iranian nurses encounter barriers in PE, and the most frequently encountered barriers were related to administration factors. These findings have implications for administrators and managers in health settings. In order to promote PE among nurses, administrators should create a supportive environment and use effective strategies to smooth the progress of PE by nurses in their practice in order to ensure optimal outcomes for patients.


Heteroleptic cationic iridium(III) complexes bearing naphthalimidyl substituents: synthesis, photophysics and reverse saturable absorption.
Three heteroleptic cationic iridium(iii) complexes containing a cyclometalating 2-[3-(7-naphthalimidylfluoren-2'-yl)phenyl]pyridine ligand and different diimine (N^N) ligands (N^N = 2,2'-bipyridine (bpy, ), 1,10-phenanthroline (phen, ), and 5,5'-bis[7-(benzothiazol-2'-yl)fluoren-2'-yl]-2,2'-bipyridine (BTF-bpy, )) were synthesized and characterized. The photophysics of these complexes was systematically investigated via spectroscopic methods and by time-dependent density functional theory (TDDFT). All complexes possess a very weak charge-transfer tail at ca. 450-570 nm; and two intense absorption bands in the region of 290-350 nm and 350-450 nm, respectively. The emission of in CH2Cl2 emanates predominantly from the C^N ligand-localized (3)π,π* state. These emitting excited states also give rise to broadband triplet excited-state absorption in the visible to the near-IR region (i.e. 420-800 nm for and , and 460-800 nm for ). The kinetics of fs transient absorption (TA) reveals that the lowest singlet excited-state lifetimes of these complexes vary from 1.43 ps to 142 ps. The stronger excited-state absorption of compared to their respective ground-state absorption in the visible spectral range leads to strong reverse saturable absorption (RSA) at 532 nm for ns laser pulses. The trend of transmission signal decrease follows > > . Extending the π-conjugation of the N^N ligand increases the strength of RSA. In addition, the naphthalimidyl (NI) substitution at the cyclometalating ligand dramatically increases the triplet excited-state lifetimes and broadens the triplet excited-state absorption to the NIR region compared to the respective Ir(iii) complexes with a benzothiazolyl substituent on the cyclometalating ligand.


Neopterin: a potential biomarker for delirium in elderly patients.
The diagnosis of delirium is not supported by specific biomarkers. In a previous study, high neopterin levels were found in patients with a postoperative delirium. In the present study, we investigated levels of neopterin, interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1) in acutely ill admitted elderly patients with and without a delirium. Plasma/serum levels of neopterin, IL-6 and IGF-1 were determined in patients aged ≥65 years admitted to the wards of Internal Medicine and Geriatrics. Differences in biomarker levels between patients with and without a delirium were investigated by the analysis of variance in models adjusted for age, gender, comorbidities and eGFR (when appropriate). Eighty-six patients were included; 23 of them with a delirium. In adjusted models, higher mean levels of neopterin (70.5 vs. 45.9 nmol/l, p = 0.009) and IL-6 (43.1 vs. 18.5 pg/ml, p = 0.034) and lower mean levels of IGF-1 (6.3 vs. 9.3 nmol/l, p = 0.007) were found in patients with a delirium compared to those without. The findings of this study suggest that neopterin might be a potential biomarker for delirium which, through oxidative stress and activation of the immune system, may play a role in the pathophysiology of delirium.


Nerve growth factor in mouse and rat serum: correlation between bioassay and radioimmunoassay determinations.
High levels of nerve growth factor (NGF) determined by competition radioimmunoassay do not agree with values obtained by bioassay. This discrepancy is illustrated here with rat and mouse serum as examples in which values up to 1000 ng/ml have been found by using competition radioimmunoassays. An explanation for the discordant results is presented: serum components bind NGF with an intermediate affinity (Kd = 10(-7) M) but with a very large capacity (up to 0.5 mg of NGF per ml of rat serum). The binding of 125I-labeled NGF to serum components competes with the binding to the solid-phase antibodies (Kd = 10(-9)M) present in limiting amounts, according to the principle of competition radioimmunoassays. Thus, less radioactivity is recovered bound to the antibodies and this gives the erroneous impression that NGF is present. To overcome this difficulty, a two-site radioimmunoassay has been developed which utilizes nonlimiting numbers of antibody binding sites. This assay provides a reliable determination of NGF levels in serum and it can be shown that in rat and mouse serum (either sex) there is less than 5 ng of NGF per ml, in agreement with the results of the bioassay.


Photoinduced charge transfer: from photography to solar energy.
To celebrate the centenary of Science Progress we offer a short survey of the progress made over the past one hundred years in the research and application of photoinduced charge transfer. After a brief historical overview and introduction to photoinduced charge transfer, we discuss developments in the theory and practice of photography, photovoltaics, photocatalysis, fluorescent probes and chemosensing.


Diffuse noxious inhibitory controls triggered by heterotopic CO2 laser conditioning stimulation decreased the SEP amplitudes induced by electrical tooth stimulation with different intensity at an equally inhibitory rate.
The purpose of this study was to investigate (1) whether selective Adelta-fiber stimulation with CO(2) laser produces a diffuse noxious inhibitory controls (DNIC) effect in the trigeminal nerve territory; and (2) whether the DNIC effect differs depending on test stimulus intensities under constant conditioning stimuli. To examine whether the CO(2) laser radiation on the dorsum of the hand selectively stimulates Adelta-fibers, laser evoked potentials (LEP) were recorded. The mean peak latency of LEP was 381.4 ms. The findings revealed that the CO(2) laser selectively stimulated Adelta-fibers. Electrical tooth stimuli with 3 levels of intensities (1.2, 1.4, 1.6 times the pain threshold) were applied to subjects as test stimulation in randomized order, with a CO(2) laser stimulus of 18 mJ/mm(2) applied to the dorsum of the hand for 4 min as the noxious conditioning stimulus. Somatosensory evoked potentials (SEP) induced by electrical tooth stimulation were recorded and tooth pain intensity was evaluated using a visual analogue scale (VAS). The amplitudes of the SEP late component and VAS values were significantly decreased only during the conditioning stimuli without aftereffect. The inhibitory rates of the amplitudes ranged from 31.3% to 34.6% and the VAS values from 29.0% to 31.2%. There were no significant differences in their inhibitory rates between the 3 test stimulus intensities. The result indicated that selective Adelta-fiber stimulation with the CO(2) laser produces a DNIC effect in the trigeminal nerve territory and suggested that the DNIC effect does not depend on the intensity of the test stimuli.


Elderly patients with an atypical presentation of illness in the emergency department.
Very little information is available on the prevalence and clinical outcome of elderly patients with atypical presentations of illness in the emergency department. The objective was to determine the prevalence and clinical outcome of elderly patients seen in the emergency department with an atypical presentation. A monocentric retrospective observational study on 355 elderly patients presenting to the emergency department. Patients of 80 years and older were included. Data were extracted from the electronic medical file. A total of 355 patients were included, with a mean age of 86 years; 53% of these elderly patients had an atypical presentation of illness. Mostly this was due to a fall (71%). A total of 15% of the patients with an atypical presentation reported no specific symptoms of the underlying disease. Patients with atypical presentation were more likely to have a longer stay in hospital (p < 0.001), to be discharged to a care institution (p = 0.000), and to have a higher delirium observation score (p < 0.001). There was no significant difference in one-year survival (p = 0.056). Atypical presentation of illness in elderly patients is highly prevalent in the emergency department. Falling accidents are the most important reason for this. Patients with an atypical presentation have a worse clinical outcome. Accurate training of emergency staff is necessary to recognise this group of patients to ensure proper clinical monitoring and timely treatment.


Research project: Charleston Bioengineered Kidney Project.
The goal of Charleston Bioengineered Kidney Project is to engineer a functional living human kidney suitable for surgical implantation using principles of directed tissue self-assembly and tissue fusion. This is a multidisciplinary project which incorporates multiple innovative bioengineering technologies and expertise from a broad spectrum of disciplines. The conceptual framework, engineering principles, design, potential cell source as well as the first preliminary data demonstrating the feasibility of the proposed Charleston Bioengineered Kidney Project are outlined. The potential challenges are described. Finally, the experts' opinion about the proposed project is also presented.


Record bandwidth and sub-picosecond pulses from a monolithically integrated mode-locked quantum well ring laser.
In this paper, we present the detailed characterization of a semiconductor ring passively mode-locked laser with a 20 GHz repetition rate that was realized as an indium phosphide based photonic integrated circuit (PIC). Various dynamical regimes as a function of operating conditions were explored in the spectral and time domain. A record bandwidth of the optical coherent comb from a quantum well based device of 11.5 nm at 3 dB and sub-picosecond pulse generation is demonstrated.


Expression of trimeric human dUTP pyrophosphatase in Escherichia coli and purification of the enzyme.
In order to rapidly purify human dUTPase, a cDNA fragment that encodes the enzyme was subcloned and expressed using the Escherichia coli plasmid vector pGEX2T. The resulting plasmid expressed high levels of a glutathione S-transferase-dUTPase fusion protein following induction with IPTG. Affinity chromatography was used to purify the fusion protein, and dUTPase was then released from the fusion protein by thrombin treatment. The purified dUTPase has two additional vector-encoded residues at the amino terminus (gly-ser), but they have no apparent effect on the activity of the enzyme since the recombinant dUTPase has catalytic properties similar to those reported for dUTPase purified from human cells (32.3 U/mg, kcat = 25 s-1, Km = 2.6 microM). Enzyme activity was inhibited by 5-mercuri-dUTP and was shown to be sensitive to EDTA. Periodate-oxidized UTP had no effect on the activity of the enzyme, and dTTP caused only slight inhibition. The results of gel filtration experiments are consistent with a homotrimeric subunit composition for dUTPase. The ability to purify human dUTPase from E. coli should allow further characterization of the enzyme and provide material for the screening of potentially useful inhibitors.


A Quartet Network Analysis Identifying Mechanically Responsive Long Noncoding RNAs in Bone Remodeling.
Mechanical force, being so ubiquitous that it is often taken for granted and overlooked, is now gaining the spotlight for reams of evidence corroborating their crucial roles in the living body. The bone, particularly, experiences manifold extraneous force like strain and compression, as well as intrinsic cues like fluid shear stress and physical properties of the microenvironment. Though sparkled in diversified background, long noncoding RNAs (lncRNAs) concerning the mechanotransduction process that bone undergoes are not yet detailed in a systematic way. Our principal goal in this research is to highlight the potential lncRNA-focused mechanical signaling systems which may be adapted by bone-related cells for biophysical environment response. Based on credible lists of force-sensitive mRNAs and miRNAs, we constructed a force-responsive competing endogenous RNA network for lncRNA identification. To elucidate the underlying mechanism, we then illustrated the possible crosstalk between lncRNAs and mRNAs as well as transcriptional factors and mapped lncRNAs to known signaling pathways involved in bone remodeling and mechanotransduction. Last, we developed combinative analysis between predicted and established lncRNAs, constructing a pathway-lncRNA network which suggests interactive relationships and new roles of known factors such as H19. In conclusion, our work provided a systematic quartet network analysis, uncovered candidate force-related lncRNAs, and highlighted both the upstream and downstream processes that are possibly involved. A new mode of bioinformatic analysis integrating sequencing data, literature retrieval, and computational algorithm was also introduced. Hopefully, our work would provide a moment of clarity against the multiplicity and complexity of the lncRNA world confronting mechanical input.


[Synergism of hyperthermia and hematoporphyrin derivative].
Much attention has been given to the photoradiation therapy, since its mechanism of effect is thought to be due to the cytotoxicity of singlet oxygen produced from hematoporphyrin derivative (HPD) by the light. We studied the effects of hyperthermia (HT) on cultured cells (T1) of ethylnitrosourea induced rat brain tumor which had uptaken HPD, because the extent of photopenetration is limited and the absorbed light is converted to heat. We used the T1 cells preincubated in Eagle MEM with 10% FCS and 2 micrograms/ml HPD, and estimated the cell survival by the colony formation using soft agar overlayer method. Synergistic effects of HT and HPD were recognized at the temperature over 41.5 degrees C-HT, suggesting that combined HT and HPD therapy could be a new promising technique. In these experiments, an increased cell proliferation was observed after temporary suppression by "insufficient hyperthermia" at 41.5 degrees C. This is a kind of rebound phenomenon, which has an important clinical implication. We should pay attention not only to the cell damage by HT but also to the outcome of the therapy which have received insufficient HT.


Obese elderly women exhibit low postural stability: a novel three-dimensional evaluation system.
The aim of this study was to evaluate the multisegmental static postural balance of active eutrophic and obese elderly women using a three-dimensional system under different sensory conditions. A cross-sectional study was conducted on 31 elderly women (16 eutrophic and 15 obese) aged 65 to 75 years. The following anthropometric measurements were obtained: weight, height, waist and hip circumference, and handgrip strength. The physical activity level was evaluated using the International Physical Activity Questionnaire. Body composition was measured using the deuterium oxide dilution technique. The Polhemus(®) Patriot (three-dimensional) equipment was used to measure the parameters of postural balance along the anteroposterior and laterolateral axes. The data acquisition involved one trial of 60 s to test the limit of stability and four trials of 90 s each under the following conditions: (1) eyes open, stable surface; (2) eyes closed, stable surface; (3) eyes open, unstable surface; and (4) eyes closed, unstable surface. For the limit of stability, significant differences were observed in the maximum anteroposterior and laterolateral displacement (p<0.01) and in the parameter maximum anteroposterior displacement in the eyes closed stable surface condition (p<0.01) and maximum anteroposterior and laterolateral displacement in the eyes open unstable surface (p<0.01 and p = 0.03) and eyes closed unstable surface (p<0.01 and p<0.01) conditions. Obese elderly women exhibited a lower stability limit (lower sway area) compared with eutrophic women, leaving them more vulnerable to falls.


Effect of inhalation of nebulized NO donor substance on acute hypoxic lung injury in newborn piglets.
Birth asphyxia may result in multiple organ dysfunction such as lung injury. Inhalation of nebulized nitric oxide precursor can selectively reduce pulmonary hypertension. However, it is unknown whether such precursors can alleviate lung injury induced by hypoxia. We evaluated the effect of inhalation of nebulized nitroglycerine and sodium nitroprusside on acute hypoxic lung injury in newborn piglets. Acute hypoxic lung injury was induced by inspiring 10% O2 for 1 hour. Twenty-four anaesthetized and mechanically ventilated piglets (5-7 days old) were randomly divided into four groups: (1) group S, not hypoxic; (2) group C, nebulized saline after hypoxia; (3) group NTG, nebulized nitroglycerine after hypoxia; (4) group SNP, nebulized sodium nitroprusside after hypoxia. Respiratory dynamic compliance and resistance of respiratory system were recorded at baseline, 0.5 hour and 1 hour of hypoxia; then 0.5 hour, 1 hour, 3 hours and 5 hours following hypoxia. After nebulization, arterial blood was collected for measuring methaemoglobin and nitrate/nitrite levels. Right lung tissue, wet-dry ratio and myeloperoxidase level were determined. White blood cell count (WBC), total surfactant phospholipids (TPL) and disaturated phosphatidyl choline (DSPC) of the bronchoalveolar lavage fluid (BALF) were calculated. Left lungs were used for examining pathological changes. No significant difference was observed in respiratory dynamic compliance, resistance of respiratory system, wet-dry ratio, levels of methaemoglobin and nitrate/nitrite after nebulization, TPL or DSPC/TPL among four groups. WBC in BALF in groups NTG and SNP significantly decreased as compared with group C: similarly for myeloperoxidase level in lung tissue. Lung histological findings showed infiltration of neutrophils in groups NTG and SNP decreased significantly as compared with group C. Inhalation of nebulized nitroglycerine or sodium nitroprusside can alleviate the infiltration of neutrophils, while it affects neither the metabolism of phospholipids nor water content in the lungs.


In Vitro Activity of Ceftazidime-Avibactam Against Enterobacteriaceae and P. aeruginosa Isolated at the Ibn Rochd University Hospital of Casablanca.
The aim of this study is to determine the in vitro activity of ceftazidime-avibactam (CZA) on Entero-bacteriaceae and P. aeruginosa strains isolated in the bacteriology-virology laboratory of the Ibn Rochd University of Casablanca. This is a prospective descriptive longitudinal study conducted from May 28 through June 25, 2022, on Enterobacteriaceae and P. aeruginosa isolated from diagnostic samples received at the Bacteriology-Virology and Hospital Hygiene Laboratory of the Ibn Rochd University Hospital of Casablanca. The isolation and identification of the strains were carried out using standard bacteriological techniques. The study of sensitivity to ceftazidime-avibactam was done by diffusion susceptibility testing on agar medium according to EUCAST 2022 recommendations. During the study period, 271 strains of Enterobacteriaceae were isolated. The sensitivity rate to ceftazidime-avibactam was 91% vs. 74% for ceftazidime alone. R. terrigena was the most resistant strain to CZA with a rate of 69%, followed by E. cloacae (14%), then K. pneumoniae (6%), and finally E. coli (5%). Among the strains isolated, 24% (n = 66) produced ESBL, of which 29% (n = 19) were resistant to CZA, and 10.7% (n = 29) were re-sistant to imipenem, including 44, 8% (n = 13) that were resistant to imipenem and CZA. Regarding P. aeruginosa, 92 strains were isolated. The CZA resistance rate was 33.6% (n = 31). Among the strains isolated, 30.4% (n = 29) were resistant to imipenem, of which 82.7% (n = 24) were resistant to CZA. The in vitro evaluation of the ceftazidime-avibactam activity on the strains isolated, mainly: E. Coli, K. Pneumoniae, and E. Cloacae, showed a good inhibitory activity of this molecule which can constitute a therapeutic alternative for the treatment of infections due to these microorganisms.


FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity.
The use of amikacin (AMK) in present treatment strategies results in severe ototoxicity; however, the underlying molecular mechanisms of this toxicity remain unclear. In this study, we investigated the effectiveness of orally administered pomegranate peel extract (PPE), a strong antioxidant, as a protective agent against AMK-induced ototoxicity. To this end, PPE was orally administered to adult BALB/c mice for 5 days, and the mice were then concurrently treated with AMK (500 mg/kg/day for 15 consecutive days). Auditory threshold shifts induced by AMK were significantly attenuated. The results of immunohistochemical staining and western blot analysis revealed that PPE exerted its protective effects by by downregulating the phosphorylation of Forkhead box O3a (FoxO3a), an important transcription factor which is involved in the responses to oxidative stress. The results also showed that PPE treatment inhibited mitogen-activated protein kinase phosphorylation, prevented the activation of pro-apoptotic protein caspase-3, decreased the levels of apoptosis-inducing Bax protein, and increased the levels of the anti-apoptotic mediator, Bcl-2, induced by AMK in the mouse cochlea. Taken together, our experimental findings suggest that phosphorylated FoxO3a mediates AMK-induced apoptosis in BALB/c mice cochlea. PPE effectively attenuated oxidative stress and ototoxicity by regulating FoxO3a, and may thus prove to be beneficial in protecting auditory cells from ototoxic drugs.


Bernstein-Greene-Kruskal solitary waves in three-dimensional magnetized plasma.
We study the width-amplitude relation for three-dimensional Bernstein-Greene-Kruskal (BGK) electrostatic solitary waves in magnetized plasmas, taking into account the dynamics of both electrons and ions. We obtain two coupled inequalities that constrain the amplitude and the widths parallel and perpendicular to the magnetic field for a Gaussian potential, and demonstrate how the solution space is further constrained by the finite temperature ratio between electrons and ions. The description is valid for both the electron and ion mode solitary waves. Our results provide a quantitative basis for understanding the ubiquity of BGK waves in widely different classes of collisionless plasmas.


Up-regulation of ETB receptor subtype mRNA by angiotensin II in rat cardiomyocytes.
The effect of angiotensin (ANG) II on the expression of endothelin (ET) receptor subtype (ETA, ETB) mRNA in cultured neonatal rat cardiomyocytes was studied. ANG II (10(-7) M) increased steady-state mRNA levels of ETB receptor, but not ETA receptor, during 6-12 hr incubation, whose effect was dose-dependent (10(-9)-10(-7) M). ANG II receptor type-1 (AT1) antagonist (CV-11974) completely inhibited the ANG II-induced up-regulation of ETB receptor, whereas the inhibitory effect by ANG II receptor type-2 (AT2) antagonist (PD 123319) was incomplete. These results suggest that ANG II up-regulates cardiac ETB receptor, predominantly via AT1 receptor.


Applications of the elastic modes of a circular plate in wavefront correction of the adaptive optics and the active optics.
The elastic modes of a general circular thin plate (EMCTP), reflecting the natural deformation of the resonance, are applied to the diffraction theory of the optical aberrations in this paper. Our work has shown that the mode shapes of the EMCTP resemble those of the Zernike polynomials. As an application example, the compensations of some low order aberrations of the 2.5 m-wide field survey telescope (WFST) have been performed with the EMCTP. Moreover, a quantitative comparative study of the active optics corrections for the EMCTP and the Zernike polynomials is presented in the numerical analysis. The quantitative analysis results have demonstrated that the efficiency of the EMCTP is superior to the standard Zernike polynomials as well as the annular Zernike polynomials.


Increased thirst and vasopressin secretion after myocardial infarction in rats.
Impaired regulation of salt and water balance in left ventricular dysfunction and heart failure can lead to pulmonary and peripheral edema and hyponatremia. Previous studies of disordered water regulation in heart failure have used models of low cardiac output with normal cardiac function (e.g., inferior vena cava ligation). We investigated thirst and vasopressin (AVP) secretion in a rat myocardial infarction model of chronic left ventricular dysfunction/heart failure in response to a 24-h water deprivation period. Thirst (implied from water drunk), hematocrit, plasma renin activity, and plasma AVP concentrations increased with water deprivation vs. ad libitum water access. Thirst and plasma AVP concentrations were significantly positively correlated with infarct size after 24-h water deprivation but not under ad libitum water access conditions. The mechanism by which this occurs is unclear but could involve increased osmoreceptor sensitivity, altered stimulation of baroreceptors, the renin-angiotensin system, or altered central neural control.


[Muti-model collaborative retrieval of chlorophyll a in Taihu lake based on data assimilation ].
Under the efforts of many scholars, large amount of remote retrieval models of water quality parameters have been developed. However, each model could only reflect the "true value" from one level because of the natural limitation of remote sensing. To get the relatively true value by combining various retrieval models, in this work, we developed a multi-model collaborative retrieval algorithm for retrieving the concentration of Chlorophyll a based on data assimilation. We measured water quality parameters and water reflectance spectra in Taihu Lake during 2006 to 2009. There were seven retrieve models established and six models were selected to participate in the multi-model collaborative retrieval algorithm. Then these selected models were combined to establish a multi-model for retrieving the concentration of Chlorophyll a. The results indicated: (1) the accuracy of multi-model retrieval algorithm was better than that of single-model retrieval method, with an optimal MAPE of only 22. 4% ; (2) with more models participating in the multi-model collaborative retrieval algorithm, the accuracy became better, the average MAPE was decreased from 25. 6% to 23. 4% , the average RMSE was decreased from 15. 082 μg.L-1 to 14. 575 μg.L-1, and the average correlation coefficient was improved from 0.91 to 0. 92; (3) the accuracy and errors of retrieval products could be effective evaluated through calculating the confidence interval, which makes possible the acquirement of spatial and temporal error distribution of Chlorophyll a concentration retrieval in Taihu Lake.


Phenotypic heterogeneity in the endothelium of the human vortex vein system.
The vortex vein system is the drainage pathway for the choroidal circulation and serves an important function in the effective drainage of the exceptionally high blood flow from the choroidal circulation. As there are only 4-6 vortex veins, a large volume of blood must be drained from many choroidal veins into each individual vortex vein. The vortex vein system must also cope with passing through tissues of different rigidity and significant pressure gradient as it transverses from the intrao-cular to the extra-ocular compartments. However, little is known about how the vortex vein system works under such complex situations in both physiological and pathological condition. Endothelial cells play a vital role in other vascular systems, but they have not been studied in detail in the vortex vein system. The purpose of this study is to characterise the intracellular structures and morphology in both the intra-and extra-ocular regions of the human vortex vein system. We hypothesise the presence of endothelial phenotypic heterogeneity through the vortex vein system. The inferior temporal vortex vein system from human donor eyes were obtained and studied histologically using confocal microscopy. The f-actin cytoskeleton and nuclei were labelled using Alexa Fluor conjugated Phalloidin and YO-PRO-1. Eight regions of the vortex vein system were examined with the venous endothelium studied in detail with quantitative data obtained for endothelial cell and nuclei size and shape. Significant endothelial phenotypic heterogeneity was found throughout the vortex vein system with the most obvious differences observed between the ampulla and its downstream regions. Variation in the distribution pattern of smooth muscle cells, in particular the absence of smooth muscle cells around the ampulla, was noted. Our results suggest the presence of significantly different haemodynamic forces in different regions of the vortex vein system and indicate that the vortex vein system may play important roles in regulation of the choroidal circulation.


"We are a Team": Couple Identity and Memory Loss.
Couplehood can be an important source of resilience in the face of memory loss, but couple identity has only recently been explored and has rarely been measured. This paper examines older spouses' descriptions of their couple identity and discusses salient themes. Data come from 19 couples from the Couples Life Story Project, a life review intervention where one partner has memory loss. Using baseline data, we analyzed how partners depicted their couple identity using a series of separate and overlapping circles. Almost half of the partners independently chose identical depictions of their relationships. An interpretative phenomenological approach revealed three major themes of couple identity: (1) doing things together and separately; (2) feelings, shared history, and closeness over time and; (3) essence of relationship. This study contributes to the small body of literature that focuses on couple identity and how partners mutually cope with aging-related challenges.


Pulmonary thrombotic microangiopathy caused by gastric carcinoma.
Pulmonary tumour thrombotic microangiopathy (PTTM) is characterised by wide spread tumour emboli along with fibrocellular intimal proliferation and thrombus formation in small pulmonary arteries and arterioles. PTTM is a rare but fatal complication of carcinoma, but the pathogenesis remains to be clarified. An autopsy case of PTTM caused by gastric adenocarcinoma is described, in which tumour cells in the PTTM lesion had positive immunoreactivity for platelet-derived growth factor (PDGF) and PDGF receptor (PDGFR), and proliferating fibromuscular intimal cells also showed expression of PDGFR. In addition, the overexpression of PGDF was detected in the alveolar macrophages. These findings suggest that PDGF derived from alveolar macrophages and from tumour cells may act together in promoting fibrocellular intimal proliferation. To the best of the authors' knowledge, the possible involvement of activated alveolar macrophages in PTTM has not been previously reported.


Cardiomyopathy in congenital complete lipodystrophy.
Molecular genetic studies have pointed to a relationship between congenital lipodystrophy syndromes and some cardiac disorders. For instance, mutations in LMNA cause either lipodystrophy or cardiomyopathy, indicating that different mutations in the same gene can produce these clinical syndromes. The present authors describe a 10-year-old female with Berardinelli-Seip congenital complete lipodystrophy (MIM 606158) caused by homozygosity for a frameshift mutation in BSCL2. In addition to the typical attributes of complete lipodystrophy, this subject had hypertrophic cardiomyopathy diagnosed in the first year of her life; its progress has been followed with non-invasive imaging. The mechanism underlying the hypertrophic cardiomyopathy in complete lipodystrophy is unclear. It may result from a direct effect of the mutant gene or it might be secondary to the effects of hyperinsulinemia on cardiac development. The variability of the associated cardiomyopathy in patients with complete generalized lipodystrophy may be caused by differential effects of mutations in the same gene or of mutations in different genes which underlie the lipodystrophy phenotype.


Use of a monoclonal antibody to evaluate integrity of the plasma membrane of stallion sperm.
Transmission electron microscopy was used to confirm that a monoclonal antibody (F79.3E2; class IgG1 kappa) was specifically localized to an antigen in the acrosomal ground substance of stallion sperm. This antibody was used to develop and validate an indirect immunofluorescent procedure to evaluate integrity of the plasma-acrosomal membranes of stallion sperm. The concept was that primary monoclonal antibody would be "shielded" from its acrosomal antigen by an intact plasma membrane. Conversely, sperm with damaged plasma-acrosomal membranes would exhibit green acrosomal fluorescence when viewed with an epifluorescence microscope. A lipophilic counterstain (red fluorescence) was used to insure that all sperm were visualized. Sperm in fresh-extended or frozen-thawed semen were incubated with hybridoma supernatant containing monoclonal antibody for 30 min at 37 degrees C, then a second antibody (rabbit anti-mouse IgG-FITC) was added for 30 min at 37 degrees C. Unbound antibody was removed by dilution and centrifugation. Sperm were resuspended in phosphate-buffered saline containing Evan's blue as a counterstain. All sperm fluoresced bright red, regardless of the status of cell membranes, except that in cells with damaged plasma-acrosomal membranes, the green fluorescence associated with antibody was overriding for the rostral portion. By counting fluorescent and nonfluorescent "acrosomes", the percentage of sperm with intact plasma-acrosomal membranes was easily determined. Evaluation of five mixtures of undamaged and damaged sperm by this procedure gave a correlation of 0.91 between the percentage of damaged sperm in a mixture and the percentage of sperm with a fluorescent acrosome. Intra- and interassay coefficients of variability were less than 6%.


Coercion in psychiatry: the importance of extramural factors.
Mechanical restraints and forced procedures in psychiatric wards are of major concern in Denmark and there is a desire to reduce these procedures to a minimum. So far, focus has primarily been on identifying and changing internal (intramural) factors when seeking to reduce coercion. To identify possible external (extramural) factors that may increase the risk of coercion during admission to a closed psychiatric ward. Using a retrospective case-controlled design, 235 patients admitted to a closed ward during 2011-2013 were randomly selected. Coercion comprised belt restraint, physical restraint, and forced medication. The data source was the electronic patient records, which include statutory information on all forced measures. Multiple logistic regression analyses were applied to calculate the risk (odds ratio, OR (95% confidence interval)) of forced measures being used. Out of the 235 patients, 66 (28%) were subject to coercion. The time of forced procedures was predominately during the first hours after admission. The risk of forced measures being applied was significantly higher if patients were involuntarily admitted (OR = 6.4 (3.4-11.9)), or were acutely intoxicated by substances at the time of admission (OR = 3.7 (1.7-8.2)). Extramural factors should be included when mental health authorities plan efforts to reduce coercion during admission to psychiatric wards. A reduced threshold for admission and improved integrated effort between mental health services and treatment for substance abuse could improve the course of disease for this group of patients and reduce the need for involuntary admissions and subsequently coercion.


Using beta-blockers to treat heart failure.
Bisoprolol, carvedilol, metoprolol, and nebivolol are beta-blocker drugs used to improve survival in patients with systolic heart failure. This article reviews these drugs and how practitioners can initiate and titrate them for maximum patient benefit.


Exploration, normalization, and genotype calls of high-density oligonucleotide SNP array data.
In most microarray technologies, a number of critical steps are required to convert raw intensity measurements into the data relied upon by data analysts, biologists, and clinicians. These data manipulations, referred to as preprocessing, can influence the quality of the ultimate measurements. In the last few years, the high-throughput measurement of gene expression is the most popular application of microarray technology. For this application, various groups have demonstrated that the use of modern statistical methodology can substantially improve accuracy and precision of the gene expression measurements, relative to ad hoc procedures introduced by designers and manufacturers of the technology. Currently, other applications of microarrays are becoming more and more popular. In this paper, we describe a preprocessing methodology for a technology designed for the identification of DNA sequence variants in specific genes or regions of the human genome that are associated with phenotypes of interest such as disease. In particular, we describe a methodology useful for preprocessing Affymetrix single-nucleotide polymorphism chips and obtaining genotype calls with the preprocessed data. We demonstrate how our procedure improves existing approaches using data from 3 relatively large studies including the one in which large numbers of independent calls are available. The proposed methods are implemented in the package oligo available from Bioconductor.


Sexual development of the urodele amphibian Pleurodeles waltl.
Pleurodeles waltl is a urodele amphibian that displays a ZZ/ZW genetic mode of sex determination involving a putative W-borne dominant determinant. This determining pathway can be environmentally inhibited since heat treated ZW larvae undergo a functional female to male sex reversal. Moreover, both genetic sexes can be reversed by treatment of larvae with steroid hormones suggesting they are the major players in the differentiation process. Indeed we demonstrated that i) aromatase expression and activity increase just before ovarian differentiation, ii) aromatase inhibitors induce a female to male sex reversal, iii) estrogens induce male to female sex reversal whereas the opposite is obtained with non-aromatizable androgens, iv) steroidogenic factor 1 and estrogen receptor alpha both display a female-enriched expression following the increase in aromatase activity. The role of endogenous hormones was investigated in a parabiosis model. Surprisingly, in ZW/ZZ associations, the ZW gonad could not differentiate suggesting that the ZZ parabiont produces an inhibiting factor, prior to ovarian differentiation. The role of AMH in this process is discussed, keeping in mind that Mullerian ducts are maintained in males. The development of antibodies and new molecular tools in the near future should help us to better understand the sexual development of this vertebrate.


Trypanosomes and haemosporidia in the buzzard (Buteo buteo) and sparrowhawk (Accipiter nisus): factors affecting the prevalence of parasites.
The prevalences of heteroxenous parasites are influenced by the interplay of three main actors: hosts, vectors, and the parasites themselves. We studied blood protists in the nesting populations of raptors in two different areas of the Czech Republic. Altogether, 788 nestlings and 258 adult Eurasian sparrowhawks (Accipiter nisus) and 321 nestlings and 86 adult common buzzards (Buteo buteo) were screened for parasites by the microscopic examination of blood smears and by cultivation. We examined the role of shared vectors and parasite phylogenetic relationships on the occurrence of parasites. In different years and hosts, trypanosome prevalence ranged between 1.9 and 87.2 %, that of Leucocytozoon between 1.9 and 100 %, and Haemoproteus between 0 and 72.7 %. Coinfections with Leucocytozoon and Trypanosoma, phylogenetically distant parasites but both transmitted by blackflies (Simuliidae), were more frequent than coinfections with Leucocytozoon and Haemoproteus, phylogenetically closely related parasites transmitted by different vectors (blackflies and biting midges (Ceratopogonidae), respectively). For example, 16.6 % buzzard nestlings were coinfected with Trypanosoma and Leucocytozoon, while only 4.8 % with Leucocytozoon and Haemoproteus and 0.3 % with Trypanosoma and Haemoproteus. Nestlings in the same nest tended to have the same infection status. Furthermore, prevalence increased with the age of nestlings and with Julian date, while brood size had only a weak negative/positive effect on prevalence at the individual/brood level. Prevalences in a particular avian host species also varied between study sites and years. All these factors should thus be considered while comparing prevalences from different studies, the impact of vectors being the most important. We conclude that phylogenetically unrelated parasites that share the same vectors tend to have similar distributions within the host populations of two different raptor species.


Evidence supporting preoperative chemotherapy for small cell carcinoma of the bladder: a retrospective review of the M. D. Anderson cancer experience.
Neuroendocrine tumors of the bladder comprise a small subset of all bladder tumors. To improve our understanding of this tumor and define outcomes with current management, we performed a retrospective review of these cases. We reviewed the records of 88 patients with small cell bladder carcinoma evaluated at our institution between 1985 and 2002. Of these patients 46 underwent cystectomy, including 25 who were treated with initial cystectomy and 21 who received preoperative chemotherapy. For patients treated with initial cystectomy median cancer specific survival (CSS) was 23 months, with 36% disease-free at 5 years. For patients receiving preoperative chemotherapy median CSS has not been reached (p = 0.026), although CSS at 5-years was 78% with no cancer related deaths observed beyond 2 years. Notably 7 of 25 patients treated with initial cystectomy received chemotherapy after surgery but their survival was no better than those treated with cystectomy alone. As others have observed, the pathological stage was higher than clinically appreciated for 56% of patients treated with initial cystectomy. Moreover, there were no cancer related deaths among patients with disease down staged to pT2 or less. Like other neuroendocrine tumors, small cell carcinoma of the bladder grows rapidly but is chemo-sensitive. Clinical under staging is the rule. Optimal results are achieved via integration of local and systemic treatment. Our results suggest that preoperative chemotherapy is the optimal strategy, even in the setting of clinically localized cancer. On the basis of these observations, we have initiated a trial in which 4 cycles of aggressive multiagent preoperative chemotherapy are followed by radical cystectomy.


Synaptic organization of primary axons in trigeminal nucleus oralis.
This report examines the morphology and synaptic connections of small-diameter primary trigeminal axons that terminate in the border zone (BZ) and ventrolateral (VL) subdivisions of rat trigeminal nucleus oralis (Vo). Primary axons were made visible for light and electron microscopic analysis by utilizing the method of anterograde transport of horseradish peroxidase. BZ receives the terminal arborizations of two different populations of small-diameter primary axons. One of these arises from unmyelinated parent fibers and terminates in the dorsal one-half of BZ, while the other has small myelinated parent branches that arborize throughout the subdivision. Terminating within VL are the arbors of a second population of small myelinated primary axons. The endings of all three populations of primary axons lie in synaptic glomeruli. Endings in both subdivisions derived from small myelinated parent fibers lie centrally in glomeruli. Those in VL form axodendritic synapses on numerous dendritic shafts and spines, while endings in BZ glomeruli make at least one axodendritic synapse on one or two dendritic shafts. Endings of unmyelinated primary axons in BZ lie at the periphery of glomeruli where each forms a single axodendritic synapse on a central dendrite. It is at these asymmetrical axodendritic synapses that these three populations of primary axons are thought to transfer their inputs directly to the dendritic arbors of second-order BZ and VL neurons. Common to all three glomeruli is one or more small axonal endings filled with flattened synaptic vesicles that establish axoaxonic synapses on the primary ending as well as axodendritic synapses on the dendritic element(s) receiving primary input. In view of their symmetrical to intermediate synaptic contacts, these endings are thought to belong to axons derived from at least one source that can inhibit or diminish the firing rate of second-order BZ and VL neurons in response to primary input.


Effect of cutting time, temperature, and calcium on curd moisture, whey fat losses, and curd yield by response surface methodology.
Response surface methodology was used to study the effect of temperature, cutting time, and calcium chloride addition level on curd moisture content, whey fat losses, and curd yield. Coagulation and syneresis were continuously monitored using 2 optical sensors detecting light backscatter. The effect of the factors on the sensors' response was also examined. Retention of fat during cheese making was found to be a function of cutting time and temperature, whereas curd yield was found to be a function of those 2 factors and the level of calcium chloride addition. The main effect of temperature on curd moisture was to increase the rate at which whey was expelled. Temperature and calcium chloride addition level were also found to affect the light backscatter profile during coagulation whereas the light backscatter profile during syneresis was a function of temperature and cutting time. The results of this study suggest that there is an optimum firmness at which the gel should be cut to achieve maximum retention of fat and an optimum curd moisture content to maximize product yield and quality. It was determined that to maximize curd yield and quality, it is necessary to maximize firmness while avoiding rapid coarsening of the gel network and microsyneresis. These results could contribute to the optimization of the cheese-making process.


Identification of an additional N-glycosylation site and thermostable mutations within the hemagglutinin-neuraminidase gene of the Newcastle disease virus belonging to the VII.1.1 sub-genotype.
Newcastle disease virus (NDV) is considered one of the most devastating avian viral patho-gens affecting the avian population, and it causes a significant economic burden on the poultry industry worldwide. The study aimed to gain deeper understanding of the molecular and phylogenetic analyses of the complete hemagglutinin-neuraminidase (HN) coding region among NDV isolates. The samples were obtained from different parts of Iran from July 2017 to February 2020, were used for phylogenic analysis in this study. The results confirmed the predominance of sub-genotype VII.1.1, previously known as sub-genotype VIIL, which is circulating in commercial broiler farms of Iran. Identification of (a) an additional N-glycosylation site (NIS) at position 144; (b) mutations S315P and I369V which are related to increasing the viral thermostability; (C) cysteine residues at positions 123; (d) amino acid substitutions in the HN antigenic sites, especially the mutations I514V and E347Q, as well as the other mutant within HN binding sites of the VII.1.1 sub-genotype, suggests the idea that this new sub-genotype of NDV may possess a high level of pathogenicity and virulence compared to other NDV sub-genotypes. In conclusion, the results indicate the presence of an additional NIS at position 144, which may alter the virulence of the isolates. Furthermore, the presence of the thermostable mutations (S315P and I369V) and the other amino acid substitutions among the VII.1.1 sub-genotype isolates may have an impact on the vaccine immunity against this new NDV sub-genotype.


A type 6 secretion system (T6SS) encoded gene within Salmonella enterica serovar Enteritidis contributes to virulence.
Bacteria interact with their host through protein secretion systems and surface structures. Pathogenic bacteria encode protein secretion systems that promote the invasion of the host's tissue, the evasion of the host's immune response, the thwarting microbial competitors, and ultimately survival within the host. For motile bacteria, the presence of extracellular flagella provides the host with a structural motif used for activation of the immune system. Within this issue of Virulence, the article "Identification of a novel gene in ROD9 island of Salmonella Enteritidis involved in the alteration of virulence-associated protein expression" describes the contribution of a gene, SEN1005, toward host-pathogen interaction. The authors demonstrate the contribution of SEN1005 to cell culture bioassays and infection in a mouse model of colitis. In each tested scenario, deletion of SEN1005 results in a phenotypic defect that was complemented by providing the SEN1005 gene in trans. SEN1005 contributes to the expression of known virulence factors within SPI-1, flagellar and chemotaxis genes, and heat shock/chaperone genes. Although much work is needed to fully elucidate the function of SEN1005, this work contributes toward our understanding of the genetic factors used by Salmonella to cause foodborne illnesses.


A Physio-Logging Journey: Heart Rates of the Emperor Penguin and Blue Whale.
Physio-logging has the potential to explore the processes that underlie the dive behavior and ecology of marine mammals and seabirds, as well as evaluate their adaptability to environmental change and other stressors. Regulation of heart rate lies at the core of the physiological processes that determine dive capacity and performance. The bio-logging of heart rate in unrestrained animals diving at sea was infeasible, even unimaginable in the mid-1970s. To provide a historical perspective, I review my 40-year experience in the development of heart rate physio-loggers and the evolution of a digital electrocardiogram (ECG) recorder that is still in use today. I highlight documentation of the ECG and the interpretation of heart rate profiles in the largest of avian and mammalian divers, the emperor penguin and blue whale.


Inhalation of glycopyrronium inhibits cigarette smoke-induced acute lung inflammation in a murine model of COPD.
Glycopyrronium bromide (GB) is a muscarinic receptor antagonist that has been used as a long-acting bronchodilator in chronic obstructive pulmonary disease (COPD) patients. The aim of this study was to investigate the anti-inflammatory activity of inhaled GB in a cigarette smoke-induced acute lung inflammation mouse model. We found that aerosol pre-treatment with GB suppresses the accumulation of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) in cigarette smoke (CS)-exposed mice. GB at doses of 300 and 600 μg/ml significantly inhibited the CS-induced increases in the mRNA and protein expression levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1 and transforming growth factor (TGF)-β1 in lung tissues and the BALF. Moreover, GB at a dose of 600 μg/ml significantly inhibited the CS-induced changes in glutathione (GSH) and myeloperoxidase (MPO) activities in the BALF, decreased the CS-induced expression of matrix metalloproteinases (MMP)-9, and increased the CS-induced expression of tissue inhibitor of metalloproteinases (TIMP)-1, as determined through the immunohistochemical staining of lung tissue. Our results demonstrate the beneficial effects of inhaled GB on the inflammatory reaction in COPD.


Effects of nutrition education and home gardening interventions on feto-maternal outcomes among pregnant women in Jimma Zone, Southwest Ethiopia: A cluster randomized controlled trial.
Although pro-dietary practices and associated malnutrition are modifiable risk factors, they have a significant effect on maternal and neonatal health outcomes. Therefore, this study aimed to assess the effect of nutritional education and home gardening promotion on feto-maternal outcomes among pregnant women. A three parallel arms community-based cluster randomized controlled trial was carried out in Jimma Zone, Southwest Ethiopia from August 2020 to January 2021. Eighteen selected clusters were randomly assigned into three arms: husband (pregnant woman with her husband), peers (pregnant woman with her peers), and the controls. A total of 348 pregnant women were recruited in a 1:1:1 allocation ratio to the study arms at the baseline and 336 attended the end-line survey. Three nutrition education sessions and four varieties of vegetable seeds were provided for women in the intervention arms (husband and peers) and only routine nutrition education for the controls. Data were collected using a pretested interviewer-administered structured questionnaire. Generalized estimating equation analysis (GEE) and one-way analysis of variance (ANOVA) and Kruskal Wallis test were used to evaluate the effect of the interventions. The intervention effect estimates were obtained through a difference-in-differences approach. In the final model, neonates born to women in the husband group were 232 g heavier than those in the control groups (β = 232, 95%CI: 228.00, 236.27. Similarly, women in the husband group had a 0.45 g/dl greater hemoglobin level than the control groups (β = 0.45, 95% CI: 36.48, 54.40). Likewise, a minimum diet diversity score was higher in the husband group as compared to the controls (β = 0.87 95% CI: (0.56, 1.18). Therefore, nutrition education and home gardening interventions resulted in a significant positive effect on the mean birth weight and maternal hemoglobin level among the intervention groups. The findings imply the need for enhancing such interventions to improve feto-maternal outcomes. The trial was registered at Pan African Clinical Trial Registry as PACTR202008624731801.


Epithelial to mesenchymal transition during gastrulation: an embryological view.
Gastrulation is a developmental process to generate the mesoderm and endoderm from the ectoderm, of which the epithelial to mesenchymal transition (EMT) is generally considered to be a critical component. Due to increasing evidence for the involvement of EMT in cancer biology, a renewed interest is seen in using in vivo models, such as gastrulation, for studying molecular mechanisms underlying EMT. The intersection of EMT and gastrulation research promises novel mechanistic insight, but also creates some confusion. Here we discuss, from an embryological perspective, the involvement of EMT in mesoderm formation during gastrulation in triploblastic animals. Both gastrulation and EMT exhibit remarkable variations in different organisms, and no conserved role for EMT during gastrulation is evident. We propose that a 'broken-down' model, in which these two processes are considered to be a collective sum of separately regulated steps, may provide a better framework for studying molecular mechanisms of the EMT process in gastrulation, and in other developmental and pathological settings.


Prenatal imaging: ultrasonography and magnetic resonance imaging.
The Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop on September 18-19, 2006, to summarize the available evidence on the role and performance of current fetal imaging technology and to establish a research agenda. Ultrasonography is the imaging modality of choice for pregnancy evaluation due to its relatively low cost, real-time capability, safety, and operator comfort and experience. First-trimester ultrasonography extends the available window for fetal observation and raises the possibility of performing an early anatomic survey. Three-dimensional ultrasonography has the potential to expand the clinical application of ultrasonography by permitting local acquisition of volumes and remote review and interpretation at specialized centers. New advances allow performance of fetal magnetic resonance imaging (MRI) without maternal or fetal sedation, with improved characterization and prediction of prognosis of certain fetal central nervous system anomalies such as ventriculomegaly when compared with ultrasonography. Fewer data exist on the usefulness of fetal MRI for non-central nervous system anomalies.


25 more midwives trained in F.P.
The 10th day of June 1993 was another day in the life of GRMA as 25 Private Midwives were awarded certificates in Family Planning Training. This is the first of 8 trainings to be held under the second phase of the Family Planning Project and was held at the Eredec Hotel, Koforidua, from 31st May - 11th June. Participants were drawn from 3 regions: Eastern 12, Volta 3, and Greater Accra 10. They were trained in Counselling of Clients and in the provision of Family Planning Services. The 3 new Trainers for the Association, with the help of the Project Director, Ms. Florence Quarcoopome, and Mrs. Charlotte Quimby, a training consultant from the US, handled the workshop. The Deputy Regional Minister, Mr. W. B. Asante, who gave the keynote address advised the participants not to waste their resources but to put all that they have learnt into practice to help mothers and children in Ghana. The Chairman of the occasion, Dr. Aaron Offei, Eastern Regional Deputy Director of Health Services, advised the participants to send in their returns correctly and on time. The participants staged a role play on dispelling of rumors in Family Planning.


The androgen receptor interacts with multiple regions of the large subunit of general transcription factor TFIIF.
The androgen receptor (AR) is a ligand-activated transcription factor that regulates genes important for male development and reproductive function. The main determinants for the transactivation function lie within the structurally distinct amino-terminal domain. Previously we identified an interaction between the AR-transactivation domain (amino acids 142-485) and the general transcription factor TFIIF (McEwan, I. J., and Gustafsson, J.-A. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 8485-8490). We have now mapped the binding sites for the AR-transactivation domain within the RAP74 subunit of TFIIF. Both the amino-terminal 136 amino acids and the carboxyl-terminal 155 amino acids of RAP74 interacted with the AR-transactivation domain and were able to rescue basal transcription after squelching by the AR polypeptide. Competition experiments demonstrated that the AR could interact with the holo-TFIIF protein and that the carboxyl terminus of RAP74 represented the principal receptor-binding site. Point mutations within AR-transactivation domain distinguished the binding sites for RAP74 and the p160 coactivator SRC-1a and identified a single copy of a six amino acid repeat motif as being important for RAP74 binding. These data indicate that the AR-transactivation domain can potentially make multiple protein-protein interactions with coactivators and components of the general transcriptional machinery in order to regulate target gene expression.


Therapeutic efficacy of the humanized JAA-F11 anti-Thomsen-Friedenreich antibody constructs H2aL2a and H3L3 in human breast and lung cancer xenograft models.
The Thomsen-Friedenreich antigen (TF-Ag-α) is found on ~85% of human carcinomas but is cryptic on normal tissue. The humanized highly specific hJAA-F11-H2aL2a and -H3L3 antibodies target TF-Ag-α without binding to TF-Ag-beta (found on surface glycolipids of some normal cells). The relative affinity of H3L3 is 17 times that of H2aL2a, which would seem to favor superior efficacy, however, increased affinity can result in less tumor penetration. To assess the potential therapeutic efficacy of these antibodies, four human cancer- mouse xenograft models were treated with H2aL2a and H3L3. The tumor xenograft models used were human non-small cell lung cancer, H520, and small cell lung cancer, HTB171 in nude mice and human triple negative breast cancer, MDA-MB-231 and HCC1806 in SCID mice. H2aL2a significantly decreased tumor growth in both breast and both lung cancer models. H2aL2a showed statistically equal or better efficacy than H3L3 and has superior production capabilities. These results suggest that H2aL2a may be superior as a naked antibody, as an antibody drug conjugate or as a radiolabeled antibody, however the higher affinity of H3L3 may lead to better efficacy in bi-specific therapies in which the binding is decreased due to the presence of only one TF-Ag-α binding site.


[Incidence and prognostic significance of inducible ventricular arrhythmias in the early post-infarction phase].
To identify patients at risk of sudden cardiac death or sustained ventricular tachycardia (VT) after recent acute myocardial infarction, 100 patients younger than 70 years (80 male, 20 female; 47 anterior wall infarction, 53 inferior wall infarction) were studied prospectively. 25 days (mean) after onset of myocardial infarction, programmed ventricular stimulation was performed, including the introduction of single (S2) and double (S2-S3) ventricular extrastimuli both during sinus rhythm and at paced ventricular cycle lengths (S1-S1) of 500, 430, 370, and 330 ms. The end of the protocol was reached as soon as 4 or more consecutive ventricular echo beats (VE) were initiated. Four or more VE were initiated in 46% of patients, 4 to 9 VE in 21%, greater than or equal to 10 VE or sustained VT in 25%. During follow-up (15 +/- 8 months), 5 patients died suddenly (less than or equal to 1 h), and 5 further patients developed spontaneous sustained ventricular tachycardia. In 3 patients who died suddenly and 4 with spontaneous sustained VT, greater than or equal to 4 VE had been induced by programmed ventricular stimulation (sensitivity 60% and 80% respectively). With regard to sudden cardiac death and spontaneous ventricular tachycardia, the predictive value of a positive test was 15%, that of a negative (normal) test 94%. False negative results occurred in 6%, whereas 85% of all abnormal results had to be regarded as false positive, as these patients did not develop an arrhythmic event during follow-up. Thus patients after recent myocardial infarction frequently have signs of increased ventricular vulnerability during programmed ventricular stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)


Retransplantation with stem cells from mismatched related donors after graft rejection in pediatric patients.
Graft failure is a life-threatening complication after transplantation of hematopoietic stem cells. We report a cohort of 11 pediatric patients with leukemias (n=8) and severe aplastic anemia (n=3) who experienced graft rejection after myeloablative transplantation from mismatched related donors (n=6) or after cord blood or matched unrelated donor transplantation (n=5). In the latter, the original donor was not available anymore. All patients were re-transplanted with CD34(+) selected or CD3/CD19 depleted stem cells from a second, haploidentical donor. Median time span from diagnosis of rejection to second transplant was 9 days. Reconditioning regimens comprised total lymphoid irradiation, thiotepa, fludarabine, ATG/OKT3 and were well tolerated. A median number of 23.5x10(6)/kg stem cells with 95,000/kg residual T-cells were infused. Sustained engraftment of neutrophiles/platelets and complete donor chimerism was achieved in all patients (ANC>500/microl: 9 (11-32) days). No GvHD>grade II was observed. 8/11 patients are disease free (median follow up 1.9 years; 1 year-EFS=72%). Causes of death were: pneumonitis, infection, relapse. Thus, haploidentical transplantation represents a realistic option to rescue patients with graft failure within a short time span, for whom a second donation from the original donor is not available. The use of different donors may contribute to avoid a second rejection.


The addition of reduced glutathione to cryopreservation media induces changes in the structure of motile subpopulations of frozen-thawed boar sperm.
Adding cryopreservation media with reduced glutathione (GSH) has previously been shown to maintain the motility, membrane integrity and fertilizing ability of frozen-thawed boar sperm, although the effects of GSH on good (GFE) and poor freezability (PFE) ejaculates rely upon the intrinsic ejaculate freezability. The resilience to withstand freeze-thawing procedures has previously been related to the existence of a specific distribution of motile sperm subpopulations, which differs between GFE and PFE. Thus, the main aim of this study was to determine whether the addition of GSH to freezing media has any impact on the distribution of motile sperm subpopulations in GFE and PFE. With this purpose, 18 GFE and 13 PFE were cryopreserved with or without 2 mM GSH. Sperm quality and motile subpopulations were evaluated at 30 min and 4 h post-thawing. Three subpopulations were identified and the percentages of spermatozoa belonging to the fastest and most linear subpopulation, which was referred as 'SP1', decreased over post-thawing time. Good freezability ejaculates that were cryopreserved in the presence of 2 mM exhibited a significantly higher percentage of spermatozoa belonging to SP1 than the other combinations of treatment and freezability both at 30 min (mean ± SEM: GFE-C: 16.6 ± 0.4; GFE-GSH 27.7 ± 0.6) and 4 h post-thawing (GFE-C: 7.8 ± 0.2 vs. 16.7 ± 0.4). In conclusion, the positive effect of GSH on the motility of frozen-thawed sperm is related to a specific sperm subpopulation (SP1), which could coincide with the fertile sperm one.


Sequential arrangement of gamma-valerolactone enantiomers enclathrated in cholic acid channels as studied by 13C solid-state NMR: elucidation of the optical resolution mechanism.
The mechanism of the optical resolution of gamma-valerolactone (VAL) enantiomers by enclathration in cholic acid (CA) channels was investigated. 13C cross-polarization magic-angle spinning spectra of CA/VAL inclusion compounds show four methyl 13C peaks of VAL with different intensities depending on the enantiomeric ratios. The four peaks were assigned to the inner and end (S)-(-)-enantiomers (S) in the S domain and the inner and end (R)-(+)-enantiomers (R). The relative intensities of the four methyl 13C peaks cannot be explained by the random process model for inclusion but are successfully reproduced by assuming the first-order Markov process, in which the inclusion probabilities of S and R depend on which enantiomer has precedingly entered the CA channel. The probability p(S/S) that two S enantiomers successively enter a channel is thus found to be 83%, and p(R/R) is 50%. The large probability of p(S/S) indicates that once an S enantiomer enters a channel, it become easy for other S enantiomers to successively enter the channel, and thus the large enantiomeric excess of S is obtained. The inclusion probabilities of S and R were confirmed by 1D 13C-13C polarization-transfer experiments among the four methyl carbons of VAL in the CA channel. Further, we found that the 13C line widths and peak positions of the CA tail group change depending on the enantiomeric ratio. We concluded that once S is included, it changes the conformation of the CA tail group so that other S enantiomers become easy to successively enter the channel.


[The use of metamizole as a risk factor in the occurrence of agranulocytosis].
The risk of agranulocytosis following the use of metamizole was studied by the method of controlled cases. All cases of agranulocytosis and their control cases in Sofia for the period 1982-1986 were included in the study. The mean agranulocytosis morbidity for this period was 3.16 cases for one million population for one year. The etiologic fraction was 7.1%. The relative risk of agranulocytosis following the use of metamizole is 1.25, the maximal risk is 0.03 cases for one million persons using metamizole for one year and the maximal lethal risk is 0.007 cases for one million persons using metamizole for one year. The use of metamizole in Bulgaria for the same period was studied, too. The data presented as a number of defined daily doses used by 1000 population for one day show that the use of metamizole in this country is high. A tendency toward an increase of 7.3% per year was found during the investigation. At the same time the agranulocytosis morbidity remained constant during the period of investigation. The results of the study lead to the conclusion that the use of metamizole is not related to a higher risk of agranulocytosis.


MicroRNA-7 inhibits the growth of human non-small cell lung cancer A549 cells through targeting BCL-2.
MicroRNAs(miRNAs) are emerging as important regulators in tumorigenesis. Increasing evidences have indicated microRNA-7(miR-7) to be a potential tumor suppressor in several human cancers. However, only a limited number of target genes have been identified so far and its biological function in Non-Small Cell Lung Cancer (NSCLC) remains to be further elucidated. In the present study, we observed a reduction of miR-7 level in NSCLC cell lines. Overexpression of miR-7 not only suppressed NSCLC A549 cells proliferation, induced cell apoptosis and inhibited cell migration in vitro, but also reduced tumorigenicity in vivo. Bioinformatics predictions revealed a potential binding site of miR-7 on 3'UTR of BCL-2 and it was further confirmed by luciferase assay. Moreover, subsequent experiments showed that BCL-2 was downregulated by miR-7 at both transcriptional and translational levels. These results suggest that miR-7 regulates the expression of BCL-2 through direct 3'UTR interactions. Therefore, we postulate BCL-2 to be a novel target possibly involved in miR-7-mediated growth suppression and apoptosis of A549 cells. These findings may provide a basic rationale for the use of miR-7 in the treatment of NSCLC.


ENDOCRINOLOGY IN PREGNANCY: Pregnancy and the incidence, diagnosing and therapy of Graves' disease.
Thyroid hormones are essential developmental factors, and Graves' disease (GD) may severely complicate a pregnancy. This review describes how pregnancy changes the risk of developing GD, how early pregnancy by several mechanisms leads to considerable changes in the results of the thyroid function tests used to diagnose hyperthyroidism, and how these changes may complicate the diagnosing of GD. Standard therapy of GD in pregnancy is anti-thyroid drugs. However, new studies have shown considerable risk of birth defects if these drugs are used in specific weeks of early pregnancy, and this should be taken into consideration when planning therapy and control of women who may in the future become pregnant. Early pregnancy is a period of major focus in GD, where pregnancy should be diagnosed as soon as possible, and where important and instant change in therapy may be warranted. Such change may be an immediate stop of anti-thyroid drug therapy in patients with a low risk of rapid relapse of hyperthyroidism, or it may be an immediate shift from methimazole/carbimazole (with risk of severe birth defects) to propylthiouracil (with less risk), or maybe to other types of therapy where no risk of birth defects have been observed. In the second half of pregnancy, an important concern is that not only the mother with GD but also her foetus should have normal thyroid function.


Berberine-Loaded Nanostructured Lipid Carriers Enhance the Treatment of Ulcerative Colitis.
Berberine (BBR), a major ingredient extracted from Coptis chinensis, is a natural drug with limited oral bioavailability. We developed nanostructured lipid carriers (NLCs) as a delivery system for enhanced anti-inflammatory activity of BBR against ulcerative colitis (UC). BBR-loaded nanostructured lipid carriers (BBR-NLCs) prepared via high-pressure homogenization were evaluated for particle size, zeta potential, drug entrapment efficiency, drug loading, drug release, toxicity, and cellular uptake. The anti-UC activities of free and encapsulated BBR were evaluated in a DSS-induced acute model of UC in mice. Spherical BBR-NLCs were prepared with a particle size of 63.96± 0.31 nm, a zeta potential of +3.16 ± 0.05 mV, an entrapment efficiency of 101.97±6.34%, and a drug loading of 6.00±0.09%. BBR-NLCs showed excellent biocompatibility in vivo. Cellular uptake experiments showed that BBR-NLCs improved uptake of BBR by RAW 264.7 cells and Caco-2 cells. Oral administration of BBR-NLCs significantly alleviated colitis symptoms (DAI, colon length, spleen swelling, MPO activity) through inhibition of NF-κB nuclear translocation, decreased expression of pro-inflammatory cytokines (IL-1β, IL-6, MMP-9, CX3CR1, COX-2, TERT), and increased expression of the tight junction protein ZO-1. BBR-loaded NLCs improved colitis symptoms, which suggested that this may be a novel formulation for treatment of UC.


The Sino-French 2012 Conference in Thoracic Oncology: an international academic platform for in-depth exchange on comprehensive research.
The Sino-French 2012 Conference in Thoracic Oncology, held November 17-18, 2012, was hosted by the Department of Thoracic Surgery at Sun Yat-sen University Cancer Center and organized in collaboration with two prestigious French hospitals: Institute Gustave Roussy and Marie Lannelongue Hospital. The conference was established by leading experts from China and France to serve as an international academic platform for sharing novel findings in basic research and valuable clinical practice experiences. Hot topics including innovation in surgical techniques, diagnosis and staging of early-stage lung cancer, minimally invasive surgery, multidisciplinary treatment of lung cancer, and progress in radiotherapy for lung cancer were explored. Highlights of the conference presentations are summarized in this report.


Synaptotagmin-7 is an asynchronous calcium sensor for synaptic transmission in neurons expressing SNAP-23.
Synchronization of neurotransmitter release with the presynaptic action potential is essential for maintaining fidelity of information transfer in the central nervous system. However, synchronous release is frequently accompanied by an asynchronous release component that builds up during repetitive stimulation, and can even play a dominant role in some synapses. Here, we show that substitution of SNAP-23 for SNAP-25 in mouse autaptic glutamatergic hippocampal neurons results in asynchronous release and a higher frequency of spontaneous release events (mEPSCs). Use of neurons from double-knock-out (SNAP-25, synaptotagmin-7) mice in combination with viral transduction showed that SNAP-23-driven release is triggered by endogenous synaptotagmin-7. In the absence of synaptotagmin-7 release became even more asynchronous, and the spontaneous release rate increased even more, indicating that synaptotagmin-7 acts to synchronize release and suppress spontaneous release. However, compared to synaptotagmin-1, synaptotagmin-7 is a both leaky and asynchronous calcium sensor. In the presence of SNAP-25, consequences of the elimination of synaptotagmin-7 were small or absent, indicating that the protein pairs SNAP-25/synaptotagmin-1 and SNAP-23/synaptotagmin-7 might act as mutually exclusive calcium sensors. Expression of fusion proteins between pHluorin (pH-sensitive GFP) and synaptotagmin-1 or -7 showed that vesicles that fuse using the SNAP-23/synaptotagmin-7 combination contained synaptotagmin-1, while synaptotagmin-7 barely displayed activity-dependent trafficking between vesicle and plasma membrane, implying that it acts as a plasma membrane calcium sensor. Overall, these findings support the idea of alternative syt∶SNARE combinations driving release with different kinetics and fidelity.


Suppurative interstitial ring keratitis due to streptococcus.
Three cases of interstitial ring abscess of the cornea caused by different strains of streptococcus are described. These infections occurred in three different clinical settings: after penetrating trauma at the limbus, after a cataract operation, and in conjunction with keratoconjunctivitis sicca. The acute appearance of a light, interstitial ring not extending to the limbus in the post-traumatized eye should alert the clinician to the possibility that a streptococcus may be responsible. The ring frequently progresses rapidly to a total ring abscess with intraocular extension. The outcome was poor in all three patients.


Structural consequence of the most frequently recurring cancer-associated substitution in DNA polymerase ε.
The most frequently recurring cancer-associated DNA polymerase ε (Pol ε) mutation is a P286R substitution in the exonuclease domain. While originally proposed to increase genome instability by disrupting exonucleolytic proofreading, the P286R variant was later found to be significantly more pathogenic than Pol ε proofreading deficiency per se. The mechanisms underlying its stronger impact remained unclear. Here we report the crystal structure of the yeast orthologue, Pol ε-P301R, complexed with DNA and an incoming dNTP. Structural changes in the protein are confined to the exonuclease domain, with R301 pointing towards the exonuclease site. Molecular dynamics simulations suggest that R301 interferes with DNA binding to the exonuclease site, an outcome not observed with the exonuclease-inactive Pol ε-D290A,E292A variant lacking the catalytic residues. These results reveal a distinct mechanism of exonuclease inactivation by the P301R substitution and a likely basis for its dramatically higher mutagenic and tumorigenic effects.


Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status.
Postabsorptive elimination of the various forms of vitamin E appears to play a key role in regulation of tissue tocopherol concentrations, but mechanisms of tocopherol metabolism have not been elucidated. Here we describe a pathway involving cytochrome P450-mediated omega-hydroxylation of the tocopherol phytyl side chain followed by stepwise removal of two- or three-carbon moieties, ultimately yielding the 3'-carboxychromanol metabolite that is excreted in urine. All key intermediates of gamma-tocopherol metabolism via this pathway were identified in hepatocyte cultures using gas chromatography-mass spectrometry. NADPH-dependent synthesis of the initial gamma- and alpha-tocopherol 13'-hydroxy and -carboxy metabolites was demonstrated in rat and human liver microsomes. Functional analysis of several recombinant human liver P450 enzymes revealed that tocopherol-omega-hydroxylase activity was associated only with CYP4F2, which also catalyzes omega-hydroxylation of leukotriene B(4) and arachidonic acid. Tocopherol-omega-hydroxylase exhibited similar binding affinities but markedly higher catalytic activities for gamma-tocopherol than alpha-tocopherol, suggesting a role for this pathway in the preferential physiological retention of alpha-tocopherol and elimination of gamma-tocopherol. Sesamin potently inhibited tocopherol-omega-hydroxylase activity exhibited by CYP4F2 and rat or human liver microsomes. Since dietary sesamin also results in elevated tocopherol levels in vivo, this pathway appears to represent a functionally significant means of regulating vitamin E status.


Beta agonist use during asthma exacerbations: how much is too much?
Overuse of inhaled beta agonist therapy is associated with risk in adult asthmatics. We report on a case of excessive short-acting and long-acting beta agonist use in the setting of a severe exacerbation of asthma, which highlights some important good practice points.