A survey of student nurses' attitudes toward help seeking for stress.
Globally, stress in student nurses may have serious implications for health, absenteeism, and attrition. Despite this, there is scant research on student nurses' attitudes toward help seeking. To examine student nurses' attitudes toward stress and help-seeking. A cross-sectional questionnaire survey design was employed to gather data from 219 student nurses at two large U.K. universities. Two-sample chi-square tests and Fisher's exact tests were used to analyze categorical associations between responses. Most had experienced stress before, believed the incidence within the profession was high, and would disclose their own stress to family/friends rather than to colleagues or professional institutions. The most popular outpatient treatment choice was social support; few would choose formal advice. The most common factor influencing inpatient treatment choice was confidentiality; for many, this factor would also lead them to seek distant rather than local inpatient care. Encouragingly, most would not lose confidence in a stressed colleague. Negative attitudes toward stress and help seeking may be entrenched even before training and may have a marked influence on how/whether students seek help. Nurse employers and educators should foster more supportive and accepting attitudes toward stress in order to tackle its unwanted consequences.


Optomechanics of a quantum-degenerate Fermi gas.
We explore theoretically the optomechanical interaction between a light field and a mechanical mode of ultracold fermionic atoms inside a Fabry-Pérot cavity. The low-lying phonon mode of the fermionic ensemble is a collective density oscillation associated with particle-hole excitations, and is mathematically analogous to the momentum side-mode excitations of a bosonic condensate. The mechanical motion of the fermionic particle-hole system behaves hence as a "moving mirror." We derive an effective system Hamiltonian that has the form of generic optomechanical systems. We also discuss the experimental consequences the optomechanical coupling in optical bistability and in the noise spectrum of the system.


Balloon kyphoplasty treatment for a spontaneous vertebral fracture in renal osteodystrophy.
Renal osteodystrophy is a spectrum of musculoskeletal abnormalities. Bony fractures can occur spontaneously or with minor trauma in this condition. The authors report the first case of balloon kyphoplasty treatment for painful renal osteodystrophy vertebral body collapse secondary to end-stage renal failure on dialysis. The authors have demonstrated that kyphoplasty is a safe procedure for pain management in severe dystrophic patients. In addition, pain treatment with kyphoplasty can be achieved without anatomical restoration of vertebral body height.


Synthesis and modification of functional poly(lactide) copolymers: toward biofunctional materials.
A polylactide copolymer with pendant benzyloxy groups has been synthesized by the copolymerization of a benzyl-ether substituted monomer with lactide. Debenzylation of the polymer to provide pendant hydroxyl groups followed by modification with succinic anhydride affords the corresponding carboxylic acid functionalized copolymer that is amenable to standard carbodiimide coupling conditions to attach amine-containing biological molecules. An amino-substituted biotin derivative was coupled to the carboxyl functional groups of copolymer films as proof-of-concept. In a demonstration of the function of these new materials, an RGD-containing peptide sequence was tethered to copolymer films at various densities and was shown to enhance the adhesion of epithelial cells. This strategy provides the opportunity for the attachment of a variety of ligands, allowing for the fabrication of a versatile class of biodegradable, biocompatible materials.


Hypothermal and hyperthermal acclimation differentially modulate cadmium accumulation and toxicity in the zebrafish.
Despite the fact that aquatic organisms are mostly poikilothermic and environmental temperature variations can have considerable impact on chemical toxicity, toxicity studies are mainly performed at the species' specific standard or optimal temperature. Since the zebrafish is a recommended test species for use in toxicity tests, we investigated the temperature dependence of 96 h cadmium accumulation and toxicity in zebrafish acclimated to 18, 26, 30 or 34°C. Zebrafish showed high cadmium tolerance with acute 96 h LC50 values of 121.5, 102.4, 124.6 and 126.7 μM at 18, 26, 30 and 34°C respectively. Differences in cadmium toxicity at the different temperatures were small and toxicity did not increase with increasing temperature as is often suggested. We did however observe an interesting concentration dependent crossover pattern in which the temperature dependence at the highest exposure concentrations was exactly opposite to the pattern at the lower concentrations. At the highest concentrations the following order of toxicity was observed: 26°C>18°C>30°C>34°C. Possibly, either the warm acclimation provoked a general stress response which protected organisms against future severe stress situations, or resulted in specific defence mechanisms which also provided protection against cadmium exposure. Although at 18°C cadmium accumulation decreased more than would be expected based on the metabolic rate, cadmium toxicity was not proportionately decreased. This increased cadmium sensitivity in the cold was likely due to the combined effect of low temperature and cadmium exposure on sodium loss. This study shows that the temperature dependence of cadmium toxicity results from the combination of altered cadmium accumulation and sensitivity. Inclusion of the temperature effect in the calculation of environmental quality standards may have to be considered to ensure that more sensitive species are also protected at suboptimal temperatures.


Heterogeneous chromosomal aberrations generate 3' truncations of the NFKB2/lyt-10 gene in lymphoid malignancies.
The NFKB2(lyt-10) gene codes for a protein that is a member of the NK-kappa B/rel family of transcription factors containing a DNA-binding rel domain and a carboxy-terminal ankyrin-like domain. The NFKB2 gene represents a candidate proto-oncogene, since it has been found to be involved in a chromosomal translocation t(10;14)(q24;q32) in one case of B-cell lymphoma and in gene rearrangements in various types of lymphoid malignancies. To elucidate the structural and functional consequences of NFKB2 rearrangements, we report the molecular characterization of three novel rearranged NFKB2 genes in lymphoid tumors. In one case of multiple myeloma (MM), cloning and sequencing analysis of reciprocal breakpoint sites showed that they occurred within intron 15 of the NFKB2 gene and led to the complete deletion of the 3' portion of the gene coding for the ankyrin domain. Fluorescent in situ hybridization (FISH) analysis showed that the novel regions involved in the NFKB2 rearrangement originated from chromosome 7q34, thus implying the occurrence of a t(7;10)(q34;q24) reciprocal chromosomal translocation. In one case of T-cell cutaneous lymphoma (CTCL) and in one of B-cell chronic lymphocytic leukemia (B-CLL), NFKB2 rearrangements occurred, respectively, within exons 18 and 20 of the gene and involved recombinations with distinct regions of chromosome 10q24. Molecular analysis suggested that these rearrangements may occur as a consequence of small internal chromosomal deletions. In both of these cases, the rearrangements led to specific carboxy-terminal truncations of NFKB2 generating abnormal transcripts that coded for proteins lacking portions of the ankyrin domain. These proteins localize in the nucleus, suggesting their constitutive activation in vivo. Overall, our results indicate that NFKB2 rearrangements in lymphoid neoplasia may occur by heterogeneous mechanisms, including internal chromosomal deletion or chromosomal translocation. The common consequence of these rearrangements appears to be the deletion of 3' sequences of NFKB2 leading to the production of carboxy-truncated constitutively nuclear proteins that may be involved in tumorigenesis.


Circadian variation of cytotoxicity and genotoxicity induced by an immunosuppressive agent "Mycophenolate Mofetil" in rats.
Immunosuppressive drugs such as Mycophenolate Mofetil (MMF) are used to suppress the immune system activity in transplant patients and reduce the risk of organ rejection. The present study investigates whether the potential cytotoxicity and genotoxicity varied according to MMF dosing-time in Wistar Rat. A potentially toxic MMF dose (300 mg/kg) was acutely administered by the i.p. route in rats at four different circadian stages (1, 7, 13 and 19 hours after light onset, HALO). Rats were sacrificed 3 days following injection, blood and bone marrow were removed for determination of cytotoxicity and genotoxicity analysis. The genotoxic effect of this pro-drug was investigated using the comet assay and the micronucleus test. Hematological changes were also evaluated according to circadian dosing time. MMF treatment induced a significant decrease at 7 HALO in red blood cells, in the hemoglobin rate and in white blood cells. These parameters followed a circadian rhythm in controls or in treated rats with an acrophase located at the end of the light-rest phase. A significant, thrombocytopenia was observed according to MMF circadian dosing time. Furthermore, abnormally shaped red cells, sometimes containing micronuclei, poikilocytotic in red cells and hypersegmented neutrophil nuclei were observed with MMF treatment. The micronucleus test revealed damage to chromosomes in rat bone marrow; the comet assay showed significant DNA damage. This damage varied according to circadian MMF dosing time. The injection of MMF in the middle of the dark-activity phase produced a very mild hematological toxicity and low genotoxicity. Conversely, it induced maximum hematological toxicity and genotoxicity when the administration occurred in the middle of the light-rest phase, which is physiologically analogous to the end of the activity of the diurnal phase in human patients.


Mechanisms of preejection and postejection velocity spikes in left ventricular myocardium: interaction between wall deformation and valve events.
Normal left ventricular myocardium demonstrates distinct spikes in the velocity trace before and after left ventricular ejection. We tested the hypothesis that the preejection and postejection velocity spikes reflect early systolic shortening and late systolic lengthening that are interrupted by mitral and aortic valve closure, respectively. In 11 anesthetized dogs, timing of valve closure was determined by pressure variables; left ventricular dimensions were determined by sonomicrometry. Myocardial shortening started 20+/-10 ms (mean+/-SD; P<0.001) before mitral valve closure and was interrupted at the time of mitral valve closure (time difference, 4+/-7 ms). Similarly, myocardial lengthening started 31+/-15 ms (P<0.001) before aortic valve closure and was interrupted at the time of aortic valve closure (time difference, 0+/-3 ms). Prevention of mitral (n=4) and aortic (n=4) valve closure by stenting the valves abolished the preejection and postejection velocity spikes, respectively. Echocardiographic measurements of patients (n=15) with severe mitral regurgitation showed that the preejection velocity spike was reduced after prosthetic valve replacement (43+/-25 versus 32+/-15 mm/s; P=0.036), indicating that preejection shortening was larger with a leaking valve. Similarly, late systolic lengthening was reduced in patients (n=15) with severe aortic regurgitation after prosthetic valve replacement; minimum postejection velocity spike was increased from -32+/-11 to -17+/-11 mm/s; P=0.0003). Asynchronous onset of contraction/relaxation and atrioventricular interaction were investigated as alternative mechanisms of the velocity spikes in dogs and patient groups but were found implausible. This study supports the hypothesis that normal left ventricular preejection and postejection velocity spikes are attributed to valve closures that interrupt early systolic shortening and late systolic lengthening, respectively.


[Contribution of orthodontics in treatment planning patients with reduced periodontium].
Orthodontics is the planned movement of teeth that can be carried thanks to the provoked resorption and apposition of osseous tissue. From the standpoint of the periodontium orthodontists should always be cognizant of the risk of iatrogenically weakening soft tissue status but at the same time they should consider that an improved character of the periodontium is one of the benefits that can be derived from mechano-therapy. These periodontal improvements, in the broadest sense of the term, can result from traditional overall therapy as well as treatment aimed solely at a local condition requiring extrusion of a tooth or, more rarely, alveolar distraction.


Segregation of Central Ventricular Conduction System Lineages in Early SMA+ Cardiomyocytes Occurs Prior to Heart Tube Formation.
The cardiac conduction system (CCS) transmits electrical activity from the atria to the ventricles to coordinate heartbeats. Atrioventricular conduction diseases are often associated with defects in the central ventricular conduction system comprising the atrioventricular bundle (AVB) and right and left branches (BBs). Conducting and contractile working myocytes share common cardiomyogenic progenitors, however the time at which the CCS lineage becomes specified is unclear. In order to study the fate and the contribution to the CCS of cardiomyocytes during early heart tube formation, we performed a genetic lineage analysis using a Sma-CreERT2 mouse line. Lineage tracing experiments reveal a sequential contribution of early Sma expressing cardiomyocytes to different cardiac compartments, labeling at embryonic day (E) 7.5 giving rise to the interventricular septum and apical left ventricular myocardium. Early Sma expressing cardiomyocytes contribute to the AVB, BBs and left ventricular Purkinje fibers. Clonal analysis using the R26-confetti reporter mouse crossed with Sma-CreERT2 demonstrates that early Sma expressing cardiomyocytes include cells exclusively fated to give rise to the AVB. In contrast, lineage segregation is still ongoing for the BBs at E7.5. Overall this study highlights the early segregation of the central ventricular conduction system lineage within cardiomyocytes at the onset of heart tube formation.


The epigenetic mechanisms involved in mitochondrial dysfunction: Implication for Parkinson's disease.
Mitochondrial dysfunction is one of the crucial factors involved in PD's pathogenicity, which emerges from a combination of genetic and environmental factors. These factors cause differential molecular expression in neurons, such as varied transcriptional regulation of genes, elevated oxidative stress, α-synuclein aggregation and endogenous neurotoxins release, which induces epigenetic modifications and triggers energy crisis by damaging mitochondria of the dopaminergic neurons (DN). So far, these events establish a complicated relationship with underlying mechanisms of mitochondrial anomalies in PD, which has remained unclear for years and made PD diagnosis and treatment extremely difficult. Therefore, in this review, we endeavored to discuss the complex association of epigenetic modifications and other associated vital factors in mitochondrial dysfunction. We propose a hypothesis that describes a vicious cycle in which mitochondrial dysfunction and oxidative stress act as a hub for regulating DA neuron's fate in PD. Oxidative stress triggers the release of endogenous neurotoxins (CTIQs) that lead to mitochondrial dysfunction along with abnormal α-synuclein aggregation and epigenetic modifications. These disturbances further intensify oxidative stress and mitochondrial damage, amplifying the synthesis of CTIQs and works vice versa. This vicious cycle may result in the degeneration of DN to hallmark Parkinsonism. Furthermore, we have also highlighted various endogenous compounds and epigenetic marks (neurotoxic and neuroprotective), which may help for devising future diagnostic biomarkers and target specific drugs using novel PD management strategies.


Sex-differences in symptoms and functioning in >5000 cancer survivors: Results from the PROFILES registry.
Previous reports highlight the greater number of side effects that women experience during cancer treatment, but little is known about sex differences in symptoms and functioning in long-term survivors. We investigated sex differences in the prevalence of physical (EORTC QLQ-C30) and emotional symptoms (Hospital Anxiety and Depression Scale) and loss of functioning (EORTC QLQ-C30) in 5339 cancer survivors (55% males). General linear models were computed to assess the differences in symptoms and functioning between female and male cancer survivors and between survivors and an age-matched reference population. The direct comparison between female and male cancer survivors identified more symptoms, such as nausea and vomiting (M = 5.0 versus. 3.2), insomnia (M = 26.1 versus. 15.9), anxiety (M = 5.2 versus. 4.2), and lower physical (M = 77.5 versus. 82.5) and emotional functioning (M = 83.4 versus. 86.3), in female survivors. However, comparison with an age-matched reference population demonstrated that several symptoms, such as fatigue, dyspnea, anxiety and depression, appeared to be more frequent in male patients. The investigation of functioning domains - compared with a reference population - highlighted further sex-specific differences. Female survivors experienced a moderate net loss in physical and cognitive functioning (-6.1 [95% CI = -8.1; -4,1] and -5.2 respectively [95% CI = -7; -3.5]), whereas male survivors displayed a significant net loss in role and social functioning compared to the reference population (-9.9 [95% CI = -11.2; -8.6] and -7.7 [95% CI = -9.6; -7.6] respectively). To adequately capture sex differences in symptoms and functioning in long-term cancer survivors, a comparison with a reference population should always be considered. In our study population, this adjustment highlighted a significant and unexpected long-term impact on male patients. Role and social functioning were especially impacted in male patients, emphasizing the need to further investigate these gendered domains.


Pseudomonas keratitis associated with continuous wear silicone-hydrogel soft contact lens: a case report.
To report a case of Pseudomonas aeruginosa culture-positive microbial keratitis in a patient wearing continuous-wear silicone hydrogel soft contact lenses. A 23-year-old white woman in good health had been wearing silicone hydrogel (lotrafilcon A) soft contact lenses continuously for 26 days when she was examined for a corneal ulcer in her left eye. She had given a history of water jet skiing and diving while wearing her contact lenses. Scrapings of the corneal ulcer were positive for P. aeruginosa, and the patient was treated with fortified topical cefazolin and gentamicin for 1 week and subsequently with topical ciprofloxacin for 2 weeks. The microbial keratitis resolved with successful treatment. However, the patient had a residual visual deficit secondary to stromal scarring. The recently introduced continuous-wear silicone hydrogel soft contact lenses, with their hyper oxygen permeability (Dk), have been shown to overcome hypoxia-associated complications and to have less P. aeruginosa binding to the corneal epithelium. Our case shows that sight-threatening microbial keratitis can still occur even with silicone hydrogel soft contact lenses. Contact lens practitioners should educate patients on the risk of sight-threatening microbial keratitis, the need for patient compliance, and prompt assessment of contact lens-related complaints.


Pregnancy and progeny in rats treated with prostaglandin A.
The effects of long-acting prostaglandin A1 upon pregnancy and fetal development were investigated in Long-Evans rats. The animals were treated by the intrauterine route either on gestational day 14 with 25 mug PGA1 or with 50 mug on day 17 of gestation. The incidence of fetal resorptions was significantly increased compared to the controls following treatment on gestational day 17. A significantly high incidence of nonspecific malformations was also induced in the offspring as a result of the treatment. There were no significant differences between experimental and control fetal and placental weights. The total protein content of fetal liver following treatment with PGA1 was not significantly reduced. Microscopic examination of placentas showed a consistent decrease in the thickness of the decidua basalis following treatment with 25 mug PGA1 on day 14 of gestation. The ovaries and umbilical cords showed no changes. In addition, treatment of rats daily with 200 mug PGA1, administered subcutaneously, on gestational days 9-12 or 12-15 did not affect the development of the conceptuses.


[Classification of manifestations in the course of infection with the human immunodeficiency virus (HIV)].
The vast number of symptoms, diseases and findings, which can be observed in the course of HIV-infection, required an arrangement in a systematic order. The classification system for adults of the Centers for Disease Control (CDC) distinguishes between 4 groups and some subgroups. Group I includes acute infection, group II asymptomatic infection, group II persistent generalized lymphadenopathy, group IV other diseases. Subgroup IV.A. stands for constitutional disease, IV.B. neurologic disease, IV.C. secondary infectious diseases, IV.D. secondary cancers and IV.E. other conditions. A somewhat different classification system is needed for children under 13 years of age. Class P-0 comprises indeterminate infection, P-1 asymptomatic infection and P-2 symptomatic infection. Subclass P-1.-A. concerns normal immune function, P-1.B. abnormal immune function, P-1.C. immune function not tested, P-2.A. nonspecific findings, P-2.B. progressive neurologic disease, P-2.C. lymphoid interstitial pneumonitis, P-2.D. secondary infectious diseases, P-2.E. secondary cancers and P-2.F. other diseases possibly due to HIV-infection.


Pharmacological effects of a vitamin K1 2,3-epoxide reductase (VKOR) inhibitor, 3-acetyl-5-methyltetronic acid, on cisplatin-induced fibrosis in rats.
Cisplatin (CDDP) is a chemotherapeutic agent that is widely used in the treatment of lymphomas and solid malignancies. However, its clinical usage is limited by its severe side effects in the kidneys. Glomerular and tubular injuries in the kidneys commonly progress to interstitial fibrosis and, ultimately, the end stage of renal failure. We previously reported that 3-acetyl-5-methyltetronic acid (AMT) had inhibitory effects on rat renal vitamin K1 2,3-epoxide reductase (VKOR) in vitro and also suppressed mesangial cell proliferation and, consequently, the formation of fibrosis via the vitamin K-dependent activation of the growth arrest-specific 6 (Gas6)/Axl pathway in anti-Thy-1 glomerulonephritis (Thy-1 GN) in rats. In the present study, we demonstrated that AMT alleviated the progression of renal fibrosis in CDDP-treated rats. The repeated intravenous administration of AMT for 28 days dose-dependently suppressed increases in plasma urea nitrogen and plasma creatinine levels as well as creatinine clearance in CDDP-treated rats. Furthermore, the treatment suppressed the expression of α-smooth muscle actin (SMA)-positive cells and ameliorated the extracellular matrix accumulation of collagen III, indicating an antifibrotic effect. In conclusion, our toxicological and histopathological results demonstrated quantitatively the pharmacological inhibitory effects of AMT on the progression of renal fibrosis in CDDP-treated rats.


MINE-BLAST TRAUMA AS A FACTOR IN THE EARLY DEVELOPMENT OF VASCULAR DISEASES OF THE BRAIN.
The aim of this study is to investigate the state of bulbar conjunctival vessels, rheological properties of blood, catecholamines (adrenaline, norepinephrine), lipid metabolism, alkaline proteins of blood serum in patients with consequences of mild combat traumatic brain injury. Materials and methods: 76 individuals aged 28 to 41 years were examined. The duration of the injury lasted from 2 to 4 years. The control group consisted of 28 individuals aged 45 to 49 years with primary cerebral atherosclerosis and manifestations of cerebral circulation disorders. The state of the bulbar conjunctiva vessels and blood circulation was studied using a slit lamp SHCHL-2B at 40-fold magnification. Rheological parameters, lipid metabolism, serum alkaline proteins, total catecholamines were studied according to generally accepted methods. Results: Changes in the vessels of the bulbar conjunctiva (stage II-III) were detected in 76% of the subjects, indicating the formation of cerebral vascular pathology, and in 87% of patients with initial cerebral atherosclerosis. The analysis of lipid metabolism showed significantly (p<0.05) increased data on all studied parameters (cholesterol, high-density lipoprotein, β-lipoprotein, atherogenic index), both in patients with aftereffects of mild combat traumatic brain injury and in patients with initial cerebral atherosclerosis. An increase in alkaline proteins indices we detected in 62% of patients with aftereffects of mild combat cerebral trauma and in 55% of patients with initial cerebral atherosclerosis. At the same time, there was an increase in total catecholamines in the erythrocytes of patients with combat head injury. An increase in fibrinogen was noted in both groups, but in the group with initial cerebral atherosclerosis it was more pronounced. Conclusions: Combat traumatic brain injury contributes to the early formation of cerebral atherosclerosis and cerebral circulation disorders in this category of patients. The examination methods we have studied should be included in the survey plan for these patients. They are important not only for diagnosis, but also for improving treatment and preventing vascular disasters.


Internanofiber Spacing Adjustment in the Bundled Nanofibers for Sensitive Fluorescence Detection of Volatile Organic Compounds.
In this work, we report the fabrication of hierarchical nanofiber bundles from a perylene monoimide molecule that enable the sensitive detection of various inert volatile organic compounds (VOCs). We demonstrate that the internanofiber spacing of the bundles with appropriate packing interactions can be effectively adjusted by various VOCs, which is in turn translated into the dynamic fluorescence responses. Upon further decreasing the size of the nanofiber bundles, of which the internanofiber spacing is more favorably adjusted, enhanced fluorescence responses to various VOC vapors can be achieved. Our work presents a new protocol, i.e., translating the stimuli-responsive internanofiber spacing into fluorescence responses, to construct novel fluorescence sensors for various hazardous chemical vapors.


The Cytochrome P450 3A4 has three Major Conformations: New Clues to Drug Recognition by this Promiscuous Enzyme.
We computed the channels of the 3A4 isoform of the cytochrome P450 3A4 (CYP) on the basis of 24 crystal structures extracted from the Protein Data Bank (PDB). We identified three major conformations (denoted C, O1 and O2) using an enhanced version of the CCCPP software that we developed for the present work, while only two conformations (C and O2 ) are considered in the literature. We established the flowchart of definition of these three conformations in function of the structural and physicochemical parameters of the ligand. The channels are characterized with qualitative and quantitative parameters, and not only with their surrounding secondary structures as it is usually done in the literature.


Discrimination between Protonation Isomers of Quinazoline by Ion Mobility and UV-Photodissociation Action Spectroscopy.
The influence of oriented electric fields on chemical reactivity and photochemistry is an area of increasing interest. Within a molecule, different protonation sites offer the opportunity to control the location of charge and thus orientation of electric fields. New techniques are thus needed to discriminate between protonation isomers in order to understand this effect. This investigation reports the UV-photodissociation action spectroscopy of two protonation isomers (protomers) of 1,3-diazanaphthalene (quinazoline) arising from protonation of a nitrogen at either the 1- or 3-position. It is shown that these protomers are separable by field-asymmetric ion mobility spectrometry (FAIMS) with confirmation provided by UV-photodissociation (PD) action spectroscopy. Vibronic features in the UVPD action spectra and computational input allow assignment of the origin transitions to the S1 and S5 states of both protomers. These experiments also provide vital benchmarks for protomer-specific calculations and examination of isomer-resolved reaction kinetics and thermodynamics.


Adhesive restorations: comparative evaluation between the adhesion of the glass-ceramics to the composite cement and the adhesion of the ceromer to the composite cement.
The aim of this work is to compare the adhesion of the glass-ceramic (empress II) to the composite cement and the adhesion of the ceromer to the composite cement. From each of the above materials, 10 little blocks, of 8 x 6 x 2 mm size, have been prepared. All the surface treatments suggested by the manufacturing industry have been performed: sandblasting and acid-etching of the ceramic, ceromer surface roughening with diamond bur and silanization and bonding application on both materials. A homogeneous layer of cement has been placed between couples of blocks of the same material and photopolymerised. Every sample, consisting of 2 bonded blocks, has been submitted to a traction force on a universal test machine connected with a computerized measure system (SINTEC D/10). Samples have been anchored to the machine binding devices by a bicomponent epoxy glue. Data on the breaking charge have been recorded and an analysis of the broken surfaces has been performed in order to classify the breaking modalities. The results ontained showed that the composite-glass-ceramic adhesion force (mean value 64 Mpa) was remarkably higher than the composite-ceromer adhesion (mean value 37.21 Mpa). The analysis of the broken surfaces by SEM showed that a mixed fracture occurred in all samples (both partly adhesive and cohesive).


Wake field in dielectric acceleration structures.
In this study we present a general approach for the analysis of the wake field of a point charge moving in a vacuum tunnel bored in dielectric material that is uniform in the direction parallel to the motion of the bunch. In the transverse direction the structure surrounding the dielectric may have arbitrary geometry. A quasianalytic expression that relates the decelerating force with the first dielectric layer, the radius of the vacuum tunnel where the charge moves, and the reflection characteristics of the structure has been developed. Simulation results for a simple structure indicate that, if the effective location where the reflection occurs in the dielectric is sufficiently apart from the edge of the vacuum tunnel, it has no effect on the point charge. In fact, the decelerating field converges exponentially as this distance increases, to the asymptotic value determined by the first dielectric layer. An estimate of the trailing wake when the structure supports a specific mode is also provided.


[Attitudes towards immunization].
Ever since vaccination was introduced, a minority has been opposed to this practice. Recently however, fear of adverse events and a general questioning of the usefulness of certain vaccines have led to wariness on the part of the broader public. In France, this phenomenon is particularly striking since the hepatitis B vaccination campaign. We wished to analyse the situation by drawing on the results of surveys conducted by the French Institute of Prevention and Health Education (Institut national de prévention et d'éducation pour la santé, INPES) which sought to gain a better understanding of health care professionals' and the general public's attitudes towards immunization. Although the majority of French men and women are convinced of the overall benefit of vaccination in the past, they increasingly question vaccine safety and usefulness today. In order to prevent further deterioration of the situation, efforts must be made to enhance public and professional awareness as to the stakes involved in the control of vaccine preventable diseases.


Design and experimental research of a 28 GHz TE01 mode 160° miter bend for electron cyclotron resonance ion source.
In this paper, a 28 GHz TE01 mode 160° miter bend employing two plane mirrors is proposed based on the quasi-optical technique and the coupled wave theory to realize high-efficiency transmission for the electron cyclotron resonance ion source. First, the TE01 mode was converted to TE0n hybrid modes with Gaussian beam characteristics by means of the designed mode converter. Second, the phase shift section was implemented to eliminate the phase difference of the hybrid modes. Then, upon reflection of two plane mirrors, the propagation direction of a wave beam is deviated by 160°. Finally, the hybrid modes were converted to the TE01 mode using the same structures of the phase shift section and the mode converter. The simulation results reveal that the TE01 mode transmission efficiency reaches 95.22% at the central frequency of 28 GHz. Additionally, the designed 160° miter bend has been fabricated, installed, and measured. The experimental results show that the power transmission efficiency reaches 98.54% including diffraction losses and ohmic losses.


A Comprehensive Needs Assessment Tool for Planning RHD Control Programs in Limited Resource Settings.
Rheumatic heart disease (RHD) is an important cause of disability and death in low- and middle-income countries. However, evidence-based interventions have not been implemented systematically in many countries. We present a RHD Needs Assessment Tool (NAT) that can be used at country or regional levels to systematically develop and plan comprehensive RHD control programs and to provide baseline data for program monitoring and evaluation. The RHD NAT follows a mixed-methods approach using quantitative and qualitative data collection instruments. Evidence is mapped to a conceptual model that follows a patient through the natural history of RHD. The NAT has 4 phases: 1) situational assessment; 2) facility-based assessment of epidemiology and health system capacity; 3) patient and provider experience of RHD using ethnographic methods; and 4) intervention planning, including stakeholder mapping and development of a monitoring and evaluation framework. The RHD NAT is designed to paint a comprehensive picture of RHD care in an endemic setting and to identify the major gaps to disseminating and implementing evidence-based interventions.


CURRENT CONCEPTS OF CANCER.
Because the cancerous change in cells appears to be a permanent alteration, handed on to daughter cells through innumerable divisions, it seems probable that it reflects an abnormality in the transfer of information from cell to daughter cells. Transfer of information in cells is believed to depend on their genetic apparatus, and transfer of abnormal information implies that the genetic apparatus is not functioning normally. Abnormalities in genetic material, whether induced by ionizing radiation, chemical compounds or viruses, would, if reproduced at cell division, reappear in daughter cells. If such abnormalities lead to cancerous change in cells, any one of these primary incitants might be effective. Under such circumstances, the nature of the primary incitant may not be the most important question, and definition of the nature of the abnormality in the genetic material may become the central problem. It may ultimately be feasible to explain the cancerous change in cells in chemical terms and to find that it represents a molecular disease which takes its origin from the emergence of abnormal nucleotide sequences in the genetic material. In biological terms this would correspond with an induced mutation which is heritable at the level of the somatic cell.


Adaptation of inner medullary collecting duct vacuolar H-adenosine triphosphatase to chronic acid or alkali loads in the rat.
Acidosis increases and alkalosis decreases proton secretion in the inner medullary collecting duct (IMCD). We examined the mechanism of this adaptation by studying the immunocytochemical distribution of the vacuolar H-adenosine triphosphatase (ATPase) in the IMCD from rats subjected to acid or alkali loads for a mean duration of 4 and 9 days. For immunocytochemical staining, a monoclonal antibody to the 31-kD subunit of the bovine kidney vacuolar H-ATPase was used. Intercalated cells were present only in the initial IMCD, and the principal cells and IMCD cells showed no appreciable H-ATPase staining under any experimental conditions. We found significant adaptive changes in the distribution of H-ATPase in the intercalated cells of the IMCD. H-ATPase staining in acid-loaded rats shifted from cytoplasmic vesicles to apical plasma membrane, whereas in alkali-loaded rats cytoplasmic vesicular staining was enhanced and staining of plasma membrane disappeared. These adaptive changes were most prominent on day 4 of acid-loaded and days 4 and 9 of alkali-loaded rats. Our results indicate that translocation of the H-ATPase pump between cytoplasmic vesicles and apical plasma membrane of the intercalated cells is an important mechanism is adaptation of the IMCD to chronic acid base perturbations.


Effects of Exercise Training on Renal Carnitine Biosynthesis and Uptake in the High-Fat and High-Sugar-Fed Mouse.
(1) Background: Diet-induced obesity inhibits hepatic carnitine biosynthesis. Herein, the effects of high-fat (HF) and high-sugar (HFHS) feeding and exercise training (ET) on renal carnitine biosynthesis and uptake were determined. (2) Methods: Male C57BL/6J mice were assigned to the following groups: lean control (standard chow), HFHS diet, and HFHS diet with ET. ET consisted of 150 min of treadmill running per week for 12 weeks. Protein levels of γ-butyrobetaine hydroxylase (γ-BBH) and organic cation transporter-2 (OCTN2) were measured as markers of biosynthesis and uptake, respectively. (3) Results: HFHS feeding induced an obese diabetic state with accompanying hypocarnitinemia, reflected by decreased free carnitine levels in plasma and kidney. This hypocarnitinemia was associated with decreased γ-BBH (~30%) and increased OCTN2 levels (~50%). ET failed to improve the obesity and hyperglycemia, but improved insulin levels and prevented the hypocarnitinemia. ET increased protein levels of γ-BBH, whereas levels of OCTN2 were decreased. Peroxisome proliferator-activated receptor-alpha content was not changed by the HFHS diet or ET. (4) Conclusions: Our results indicate that ET prevents the hypocarnitinemia induced by HFHS feeding by increasing carnitine biosynthesis in kidney. Increased expression of OCTN2 with HFHS feeding suggests that renal uptake was stimulated to prevent carnitine loss.


Chemotherapy-induced O(6)-benzylguanine-resistant alkyltransferase mutations in mismatch-deficient colon cancer.
The ability of O(6)-benzylguanine (BG) to inactivate alkyltransferase (AGT) to potentiate the antitumor efficacy of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) is being tested in clinical trials. As of now, there are no examples of acquired resistance to BG+BCNU in the clinical setting. However, we hypothesized that genetically unstable tumors might develop resistance to the combination after repeated drug-exposures to achieve therapeutic efficacy. To evaluate this possibility, we treated three colon cancer cell lines that are either proficient in mismatch repair (MMR) [SW480 (MMR wild type)] or deficient in MMR [HCT116 (hMLH1 mutant) and HCT15 (hMSH6 mutant)] with three cycles of BG+BCNU. After drug-treatments, HCT116 and HCT15 were completely resistant to BG-potentiated cytotoxicity of BCNU. In these two cell lines, the acquired BG resistance resulted from two de novo and different mutations at amino acid 165 in AGT: 165-lysine (K) to glutamic acid (E) (K165E in HCT116), and 165-lysine to asparagine (N) (K165N in HCT15). Both K165-mutated AGTs had markedly decreased enzymatic activity because of unstable AGT protein but were remarkably resistant to BG inactivation. FISH analysis showed that only one copy of MGMT gene exists in HCT116 cells, and the status of promoter methylation of MGMT in HCT15 showed that one allele of the MGMT promoter has an aberrant methylation. Thus, the MGMT gene expressing AGT either from one copy (HCT116) or from unmethylated allele (HCT15) was mutated because of the exposure to BG+BCNU in these two MMR-deficient cell lines. Conversely, MMR-proficient SW480 cells, treated with three cycles of BG+BCNU, maintained wt AGT and the sensitivity to BG-potentiated BCNU-cytotoxicity. To confirm that K165-mutated AGT proteins were responsible for resistance to BG+BCNU, we transfected K165E and K165N MGMT cDNAs into Chinese hampster ovary (CHO) cells. Transfected CHO cells had low AGT activity but increased IC(50) for either BCNU or temozolomide (TMZ), compared with parental CHO cells. BG did not potentiate the cytotoxicity of these two alkylating agents at concentrations up to 200 microM; in contrast, BG, at 25 microM, sensitized CHO-AGT (transfected with wt MGMT cDNA) cells to BCNU or TMZ-cytotoxicity by 3-4 fold. These results suggest that K165 AGT mutants arising in MMR-deficient tumor cells after treatment with chemotherapeutic agents are both resistant to BG-inactivation and are active in the repair of alkylated DNA adducts.


Public health and aging: influenza vaccination coverage among adults aged > or =50 years and pneumococcal vaccination coverage among adults aged > or =65 years--United States, 2002.
Vaccination of persons at risk for complications from influenza and pneumococcal disease is a key public health strategy in preventing morbidity and mortality in the United States. During the 1990-1999 influenza seasons, approximately 36,000 deaths were attributed annually to influenza infection, with approximately 90% of deaths occurring among adults aged > or =65 years. In 1998, an estimated 3,400 adults aged > or =65 years died as a result of invasive pneumococcal disease. One of the national health objectives for 2010 is to achieve 90% coverage of noninstitutionalized adults aged > or =65 years for both influenza and pneumococcal vaccinations (objective no. 14.29). In 2000, the Advisory Committee on Immunization Practices (ACIP) broadened the universal recommendations for influenza vaccination to include adults aged 50-64 years in addition to adults aged > or =65 years. To assess progress toward achieving the 2010 national health objective and implementing the ACIP recommendations, CDC analyzed data from the 2002 Behavioral Risk Factor Surveillance System (BRFSS). This report summarizes the results of that analysis, which indicate that influenza and pneumococcal vaccination levels among adults aged > or =65 years and influenza vaccination levels among adults aged 50-64 years varied widely among states/areas and racial/ethnic populations. Innovative approaches are needed to increase vaccination coverage, particularly among certain populations.


Molecular epidemiology of infectious bronchitis virus and avian metapneumovirus in Greece.
Respiratory diseases like infectious bronchitis virus (IBV) and avian metapneumovirus (aMPV) have been held accountable for major losses for poultry production. Nevertheless, scarce information was present dealing with the prevalence and molecular epidemiology of these infections in Greece and the efficacy of currently applied control strategies. To fill this gap, a specific epidemiological study was designed. A total of 106 broiler and layer farms, including 10 backyard and 96 commercial flocks, were sampled between March 2016 and May 2017, and the obtained tracheal swabs were tested for IBV and aMPV using RT-PCR based techniques followed by sequencing. For each farm, data regarding production type, flock features, clinical signs, and vaccination program were also recorded. Different associations between vaccination protocol, production type, animal category, birds density, age, presence of clinical signs, and IBV and/or aMPV infection were tested. Both IBV and aMPV field strain prevalence were proven high, approximately 20 and 30%, respectively, being the GI-19 lineage (14 out of 19; 73.6%) and B subtype (30 out of 30; 100%), the most commonly detected IBV and aMPV genetic types. Infection with IBV field strains was significantly associated with clinical sign presence (odds ratio = 8.55 [95CI = 2.17-42.90]). Remarkably, only the vaccination protocol involving a double vaccination at 1 D of age was proven protective against IBV-induced symptomatology, with the odds of developing disease being 4.14 [95CI = 1.34-14.51] times lower. No association was demonstrated between aMPV infection and clinical outbreaks or between aMPV and IBV detection, suggesting the marginal role of the former pathogen in poultry farming. Globally, the present study provides the first detailed investigation of the epidemiological scenario of 2 viruses traditionally considered of pivotal relevance in poultry farming and demonstrates that remarkable benefits could be obtained with just minor adjustments in vaccination protocols.


Concurrence of villous adenoma and non-muscle invasive bladder cancer arising in the bladder: a case report and review of the literature.
Villous adenoma arising in the urinary tract is rare tumor. Most cases have been identified as benign neoplasm in the colon. Villous adenoma of the gastrointestinal tract is thought arise from premalignant polyps. Here, we report a case of concurrence of villous adenoma and non-muscle invasive bladder cancer. An 85-year-old woman presented at our office because of gross hematuria. Cystoscopic examination detected two papillary tumors in the bladder. Each tumor was resected and diagnosed, respectively. Histopathology confirmed that the resected one tumor was a villous adenoma, and the other was urothelial carcinoma (T1, high grade). Immunostaining for cytokeratin (CK) 7, CK20 and Ki-67 confirmed that CK7: (-), CK20: (+) and Ki-67: (<=30%) in villous adenoma while CK7: (+), CK20: (+), and Ki-67: (70%) in urothelial carcinoma. Three months later from TUR, urothelial carcinoma recurred in the trigone. She received adjuvant intravesical immunotherapy with BCG post TUR for the recurrence site. There were no specific findings on ultrasonography, CT, MRI or cystoscopic examination morphologically. Therefore, pre-pathological villous adenoma of the bladder is extremely difficult to diagnose. There are some case reports of solitary villous adenoma in the bladder or with coexisting adeno carcinoma. However, to the best of our knowledge, this is only the second report of villous adenoma in the bladder of coexisting urothelial carcinoma that has been published in the literature. Premalignant villous adenoma of the bladder is extremely rare and difficult to diagnose without histologic examination. Any suspicious lesion of the bladder should be biopsied and/or resected to confirm histology.


Implementation of the Anammox process for improved nitrogen removal.
Stringent standards for nitrogen discharge necessitate the implementation of new systems for the sustainable removal of ammonium from wastewater. One of such systems is based on the process of anaerobic ammonium oxidation (Anammox), which is a new powerful tool especially for strong nitrogenous wastewaters. In this study, the Anammox process performance was tested with synthetic wastewater in a completely stirred tank reactor (CSTR). The reactor was operated for 511 days and fed with increasing amounts of ammonium and nitrite. In this period, an increase of ammonium and nitrite utilization rates were observed as a result of the increase of nitrogen loads in the influent. After 272 days, about 60% of the biomass was removed from the reactor and the system was restarted. Throughout 511 days 90% of the ammonium and more than 99% of the nitrite were converted mainly to dinitrogen (N2) and nitrate. The microbial community in the reactor was characterized with Fluorescence in situ Hybridization (FISH). The study showed that the population in the reactor was dominated by the deep-branching planctomycete Candidatus "Brocadia anammoxidans" strain Dokhaven 2.


[Maternal diabetes and fetal hypoxia].
Perinatal mortality has not decreased in type 1 diabetic pregnancies during the last 30 years. Fetal deaths are five times and neonatal deaths three times higher compared with the general population. Chronic intrauterine hypoxia caused by maternal diabetes is the most likely cause of stillbirths during the last weeks of pregnancy. Both fetal hyperglycemia and hyperinsulinemia can independently cause fetal chronic hypoxia by increasing fetal oxygen consumption. Fetal chronic hypoxia can be detected antenatally by measuring amniotic fluid erythropoietin concentration. Prepregnancy visits for advice and glycemic control should be increased among diabetic women. Furthermore, pregnancy surveillance should be enhanced and therapeutic strategies changed in order to improve perinatal outcome among diabetic pregnancies.


Edelfosine protects precultured heart fragments against the invasion of malignant cells through altered sialylation.
1-O-octadecyl-2-O-methylglycero-3-phosphocholine (ET-18-OMe)-treated precultured heart fragments (PHF) are resistant to the invasion of malignant cells. Previous studies have demonstrated that this effect is due to the alterations of the N-linked glycoproteins in PHF after 48-h ET-18-OMe treatment. Moreover, the observed effect was still present seven days after ET-18-OMe was omitted. The present study reveals that approximately 13.4% of the administered ET-18-OMe was taken up by PHF and about 75% of the initial uptake was still present after ET-18-OMe was removed. In addition, we found significant changes in the sialic acid content and sialyltransferase activities in both conditions. Overall, these results clearly demonstrate that the uptake and retention of ET-18-OMe are responsible for the resistance to the invasion of malignant cells due to the altered sialylation of the cell surface glycoproteins in PHF.


Use of ultrasound to diagnose pneumothorax after video assisted thoracic surgery: Do we need to acquire a new skill?
Diagnosis of a pneumothorax in the immediate post-operative area can be difficult. Traditional gold-standard modalities may not be available or feasible to institute. Ultrasound (US) guidance allows the anesthesia provider a method of quickly detecting this potentially life-threatening complication especially when it's least expected. We encountered such a case when a 40 years male patient posted for video assisted thoracic surgery for drainage of empyema on left side of chest developed pneumothorax on right side post-operatively. Timely diagnosis with the help of US saved time and his life. We thus want to emphasize the importance of this simple but useful skill to the anesthesiologist.


Closure of Large Myelomeningocele Defects Using the O-S Flap Technique.
Meningomyelocele is a kind of spina bifida. In this deformity, the spinal canal and the back bone is open. This type of birth defect is also called a neural tube defect. There are many and different methods on the closure of large meningomyelocele defects. Although small meningomyeloceles may be agreeable to direct or primary closure with the local surrounding skin, the closure of large meningomyelocele skin defects needs more complex methods. The author presented a different surgical procedure for the closure of large meningomyelocele defects. The authors presented 9 neonates treated with an O-S (O is the shape of the defect, and S is the final scar shape) advancement procedure. After neurosurgical repair of the placode performed, the skin defect is closed with the O-S flap. This flap method is used for the closure of large meningomyelocele defects in 8 patients, aged between 4 days to 3 months. The defect size was 9.0 to 12.0 cm to 5.3 to 8.5 cm on an average. Mean follow-up was 9.25 months (range: 2-19 months). In all patients, there was no any flap ischemia, and the tension-free 1-stage closure was ensured. All patients healed without any complication. In one patient, cerebrospinal fluid leakage was observed. Revision surgery was done for this patient. No wound dehiscence was seen at follow-up period. The major advantages of this technique are: defects can be closed with only 2 incisions, short operative time, and there is no additional muscle transfer. Our suggested technique also provides a well-vascularized cutaneous tissue covering over the neural tissues. This suggested new technique seems to be a safe and practical solution for closure of the large meningomyelocele defects.


Automated Catheter Navigation With Electromagnetic Image Guidance.
This paper describes a novel method of controlling an endoscopic catheter by using an automated catheter tensioning system with the objective of providing clinicians with improved manipulation capabilities within the patient. Catheters are used in many clinical procedures to provide access to the cardiopulmonary system. Control of such catheters is performed manually by the clinicians using a handle, typically actuating a single or opposing set of pull wires. Such catheters are generally actuated in a single plane, requiring the clinician to rotate the catheter handle to navigate the system. The automation system described here allows closed-loop control of a custom bronchial catheter in tandem with an electromagnetic tracking of the catheter tip and image guidance by using a 3D Slicer. An electromechanical drive train applies tension to four pull wires to steer the catheter tip, with the applied force constantly monitored through force sensing load cells. The applied tension is controlled through a PC connected joystick. An electromagnetic sensor embedded in the catheter tip enables constant real-time position tracking, whereas a working channel provides a route for endoscopic instruments. The system is demonstrated and tested in both a breathing lung model and a preclinical animal study. Navigation to predefined targets in the subject's airways by using the joystick while using virtual image guidance and electromagnetic tracking was demonstrated. Average targeting times were 29 and 10 s, respectively, for the breathing lung and live animal studies. This paper presents the first reported remote controlled bronchial working channel catheter utilizing electromagnetic tracking and has many implications for future development in endoscopic and catheter-based procedures.


Age structure affects population productivity in an exploited fish species.
Long-term changes in the age and size structure of animal populations are well documented, yet their impacts on population productivity are poorly understood. Fishery exploitation can be a major driver of changes in population age-size structure because fisheries significantly increase mortality and often selectively remove larger and older fish. Climate change is another potential driver of shifts in the demographic structure of fish populations. Northeast Arctic (NEA) cod is the largest population of Atlantic cod (Gadus morhua) and one of the world's most important commercial fish stocks. This population has experienced considerable changes in population age-size structure over the past century, largely in response to fishing. In this study, we investigate whether changes in spawner age structure have affected population productivity in NEA cod, measured as recruits per spawning stock biomass, over the past 75 years. We find evidence that shifts in age structure toward younger spawners negatively affect population productivity, implying higher recruitment success when the spawning stock is composed of older individuals. The positive effect of an older spawning stock is likely linked to maternal effects and higher reproductive output of larger females. Our results indicate a threefold difference in productivity between the youngest and oldest spawning stock that has been observed since the 1950s. Further, our results suggest a positive effect of environmental temperature and a negative effect of intraspecific cannibalism by older juveniles on population productivity, which partly masked the effect of spawner age structure unless accounted for in the model. Collectively, these findings emphasize the importance of population age structure for the productivity of fish populations and suggest that harvest-induced demographic changes can have negative feedbacks for fisheries that lead to a younger spawning stock. Incorporating demographic data into harvest strategies could thus facilitate sustainable fishery management.


Effects of nonthermal preservation technologies on antioxidant activity of fruits and vegetables: A review.
Consumer demand for safe and nutritious fruits and vegetables has given rise to the development of a number of nonthermal food preservation techniques. Recent studies have highlighted that antioxidant activity of fruits and vegetables plays an important role in human health. In this paper, the influences of nonthermal preservation technologies, including pulsed electric field, radiation processing, dense phase carbon dioxide, ozone processing, and edible coatings, on the antioxidant capacity and related compounds in fruits and vegetables are reviewed. The proposed mechanisms and future trends are also discussed to accelerate the further commercialization and exploration of these novel technologies, which will, in turn, help to promote human health.


Bacterial Profile And Antibiogram Of Otitis Media Among Children In Yemen.
Otitis media is a worldwide disease and is higher in developing countries, particularly among the low socioeconomic levels of the society. The aim of the study is to identify the bacterial etiologic agents of otitis media (OM) and their antibiotics sensitivity patterns among children in Specialized Sam Paediatric Centre (SSPC) and Al-Mamoon Diagnostic Medical Centre (AMDC), in Sana'a city. A cross-sectional study was done in SSPC and AMDC from January to October 2015. A total of 150 patients who had ear pus discharge and clinically diagnosed as OM were included in this study. Samples of ear discharge were collected, bacteriologically tested by standard methods and bacterial strains were identified using biochemical testes. Questionnaire was administered on patients or parents that cover the age, gender and the duration of symptoms. A total of 150 children with OM, their age ranged from below 1-15 years (85 males and 65 females). Children less than 5 years of age were 100 and 50 with age ranged from 6-15 years. Bacterial isolates were Staphylococcus aureus (44%), Pseudomonas aeruginosa (12.67%), Enterococcus species (12.67%), and Streptococcus pneumonia (10%). Bacterial culture revealed that, Staphylococcus aureus sensitivity to cefotaxime and azithromycin was 98%, to amoxicillin-clavulanic acid was 92% and it was 85% to gentamicin. Pseudomonas aeruginosa sensitivity to cefotaxime was 100%, to azithromycin and gentamicin was 98% and it was 80% to cefaclor. Enterococcus sensitivity to amoxicillin-clavulanic acid was 85%, to azithromycin was 80%, and it was 75% to cefotaxime, and gentamicin. The most common microorganism isolated was Staphylococcus aureus followed by Pseudomonas, Enterococcus species, and then Streptococcus pneumonia. The most effective antibiotics were cefotaxime, amoxicillin-clavulanic acid, azithromycin and gentamicin. Therefore, knowledge of antimicrobial susceptibility test is essential for guiding appropriate antibacterial therapy.


A comparative study-efficacy and safety of combined spinal epidural anesthesia versus spinal anesthesia in high-risk geriatric patients for surgeries around the hip joint.
Combined spinal epidural anesthesia (CSEA) has a significant advantage by enabling the use of low dose intrathecal local anesthetic, with knowledge that the epidural catheter may be used to extend the block as necessary. CSEA is useful in high-risk geriatric patients by providing greater hemodynamic stability. This study is designed to compare the clinical effects of CSEA versus spinal anesthesia in high-risk geriatric patients undergoing surgeries around the hip joint. Sixty patients aged >65 years, American Society of Anaesthesiology III and IV were randomly allocated into two equal groups. Group A (n = 30) received CSEA with 1 ml (5 mg) of 0.5% hyperbaric bupivacaine with 25 μg fentanyl through spinal route, and the expected incompleteness of spinal block was managed with small incremental dose of 0.5% isobaric bupivacaine through epidural catheter, 1-1.5 ml for every unblocked segment to achieve T10 sensory level. Group B (n = 30) received spinal anesthesia with 2.5 ml (12.5 mg) of 0.5% hyperbaric bupivacaine and 25 μg fentanyl. Both the groups showed rapid onset, excellent analgesia and good quality motor block. Group A showed a significantly less incidence of hypotension (P < 0.01) along with the provision of prolonging analgesia as compared to Group B. CSEA is a safe, effective, reliable technique with better hemodynamic stability along with the provision of prolonging analgesia compared to spinal anesthesia for high-risk geriatric patients undergoing surgeries around the hip joint.


Phosphorus May Induce Phenotypic Transdifferentiation of Vascular Smooth Muscle Cells through the Reduction of microRNA-145.
Phosphorus is a vital element for life found in most foods as a natural component, but it is also one of the most used preservatives added during food processing. High serum phosphorus contributes to develop vascular calcification in chronic kidney disease; however, it is not clear its effect in a population without kidney damage. The objective of this in vivo and in vitro study was to investigate the effect of high phosphorus exposure on the aortic and serum levels of miR-145 and its effect on vascular smooth muscle cell (VSMCs) changes towards less contractile phenotypes. The study was performed in aortas and serum from rats fed standard and high-phosphorus diets, and in VSMCs exposed to different concentrations of phosphorus. In addition, miR-145 silencing and overexpression experiments were carried out. In vivo results showed that in rats with normal renal function fed a high P diet, a significant increase in serum phosphorus was observed which was associated to a significant decrease in the aortic α-actin expression which paralleled the decrease in aortic and serum miR-145 levels, with no changes in the osteogenic markers. In vitro results using VSMCs corroborated the in vivo findings. High phosphorus first reduced miR-145, and afterwards α-actin expression. The miR-145 overexpression significantly increased α-actin expression and partially prevented the increase in calcium content. These results suggest that miR-145 could be an early biomarker of vascular calcification, which could give information about the initiation of the transdifferentiation process in VSMCs.


Dynamic expression of FKBP5 in the medial prefrontal cortex regulates resiliency to conditioned fear.
The factors influencing resiliency to the development of post-traumatic stress disorder (PTSD) remain to be elucidated. Clinical studies associate PTSD with polymorphisms of the FK506 binding protein 5 (FKBP5). However, it is unclear whether changes in FKBP5 expression alone could produce resiliency or susceptibility to PTSD-like symptoms. In this study, we used rats as an animal model to examine whether FKBP5 in the infralimbic (IL) or prelimbic (PL) medial prefrontal cortex regulates fear conditioning or extinction. First, we examined FKBP5 expression in IL and PL during fear conditioning or extinction. In contrast to the stable expression of FKBP5 seen in PL, FKBP5 expression in IL increased after fear conditioning and remained elevated even after extinction suggesting that IL FKBP5 levels may modulate fear conditioning or extinction. Consistent with this possibility, reducing basal FKBP5 expression via local infusion of FKBP5-shRNA into IL reduced fear conditioning. Furthermore, reducing IL FKBP5, after consolidation of the fear memory, enhanced extinction memory indicating that IL FKBP5 opposed formation of the extinction memory. Our findings demonstrate that lowering FKBP5 expression in IL is sufficient to both reduce fear acquisition and enhance extinction, and suggest that lower expression of FKBP5 in the ventral medial prefrontal cortex could contribute to resiliency to PTSD.


Identification of hub genes and their novel diagnostic and prognostic significance in pancreatic adenocarcinoma.
The main reasons for the poor prognoses of pancreatic adenocarcinoma (PA) patients are rapid early-stage progression, advanced stage metastasis, and chemotherapy resistance. Identification of novel diagnostic and prognostic biomarkers of PA is therefore urgently needed. Three mRNA microarray datasets were obtained from the Gene Expression Omnibus database to select differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for hub genes were performed using DAVID. Correlations between expression levels of hub genes and cancer-infiltrating immune cells were investigated by TIMER. Cox proportional hazard regression analyses were also performed. Serum hub genes were screened using the HPA platform and verified for diagnostic value using ELISAs. We identified 59 hub genes among 752 DEGs. GO analysis indicated that these 59 hub genes were mainly involved in the defense response to viruses and the type I interferon signaling pathway. We also discovered that RSAD2 and SMC4 were associated with immune cell infiltration in the PA microenvironment. Additionally, DLGAP5 mRNA might be used as an independent risk factor for the prognoses of PA patients. Furthermore, the protein encoded by ISG15, which exists in peripheral blood, was validated as a potential diagnostic biomarker that distinguished PA patients from healthy controls (area under the curve: 0.902, 95% confidence interval: 0.819-0.961). Our study suggested that RSAD2 and SMC4 were associated with immune cell infiltration in the PA microenvironment, while DLGAP5 mRNA expression might be an independent risk factor for the survival prognoses of PA patients. Moreover, ELISAs indicated that serum ISG15 could be a potential novel diagnostic biomarker for PA.


Basic science and clinical research advances in the pituitary transcription factors: Pit-1 and Prop-1.
The pituitary-specific transcription factors, Pit-1 (also called Pou1f1) and prophet of Pit-1 (Prop-1), are critical for normal pituitary development and function. The aim of the present review is to highlight the recent basic science and clinical research advances in these transcription factors, as they relate to signaling pathway interactions, gene regulation, and mutations in human diseases. A number of important basic research discoveries have been made in the area of the pituitary-specific transcription factors, Pit-1 and Prop-1. Among these findings include: the effects of the Pit-1 coactivators, GATA-2 and TRAP-220, on the transcriptional regulation of the TSHbeta gene and thyrotropin expression, characterization of a novel pituitary regulator of Pit-1 expression, Atbf1, elucidation of the roles of Wnt and Notch signaling on Prop-1-mediated specification of the Pit-1 cell lineage and gonadotropes, and the identification of regulatory regions of the Prop-1 gene. Advances in clinical research include: the identification of novel mutations in the human POU1F1 and PROP-1 genes, and screening guidelines for patients with combined pituitary hormone deficiencies and possible mutations in these transcription factors. Research into the complex interplay of signaling pathways and transcription factors that regulate the pituitary gland are important areas of developmental biology and normal physiology. Clinically, such research has important implications for human diseases by identifying inheritable transcription factor mutations that may cause pituitary hormonal deficiencies.


Expression of Axl and its prognostic significance in human breast cancer.
Breast cancer is the most common malignant cancer and second leading cause of cancer-related death among women, and its prevalence continues to increase. Axl overexpression has been identified in the many types of human cancer, and it has been demonstrated to participate in signaling pathways related to carcinogenesis and cancer development. In the present study, Axl expression was examined by performing immunohistochemical staining in 60 breast cancer tumors and 40 benign breast lesions (25 mammary dysplasia and 15 breast fibroadenoma). In total, 34 (56.67%) cancer tissues and 13 (32.5%) benign breast lesions were classified as exhibiting high levels of Axl expression, indicating a significant association between malignancy and high Axl expression. High Axl expression was also associated with estrogen receptor (ER) positivity (P=0.028), progesterone receptor (PR) positivity (P=0.007), and poor tumor differentiation (P=0.033). No significant associations were observed between Axl expression and age, tumor size, lymph node metastasis, tumor node metastasis staging, human epidermal growth factor receptor 2 and Ki67 antigen. The Kaplan-Meier survival analysis and Cox proportional hazard model both demonstrated that there was no statistical difference between Axl expression and breast cancer prognosis. However, it remains unclear whether the expression of Axl is correlated with the prognosis of luminal type breast cancer patients.


Associations between polycyclic aromatic hydrocarbon (PAH) exposure and oxidative stress in people living near e-waste recycling facilities in China.
Emission of polycyclic aromatic hydrocarbons (PAHs) from e-waste recycling activities in China is known. However, little is known on the association between PAH exposure and oxidative damage to DNA and lipid content in people living near e-waste dismantling sites. In this study, ten hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and two biomarkers [8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA)] of oxidative stress were investigated in urine samples collected from people living in and around e-waste dismantling facilities, and in reference population from rural and urban areas in China. The urinary levels of ∑10OH-PAHs determined in e-waste recycling area (GM: 25.4μg/g Cre) were significantly higher (p<0.05) than those found in both rural (11.7μg/g Cre) and urban (10.9μg/g Cre) reference areas. The occupationally exposed e-waste workers (36.6μg/g Cre) showed significantly higher (p<0.01) urinary Σ10OH-PAHs concentrations than non-occupationally exposed people (23.2μg/g Cre) living in the e-waste recycling site. The differences in urinary Σ10OH-PAHs levels between smokers (23.4μg/g Cre) and non-smokers (24.7μg/g Cre) were not significant (p>0.05) in e-waste dismantling sites, while these differences were significant (p<0.05) in rural and urban reference areas; this indicated that smoking is not associated with elevated levels of PAH exposure in e-waste dismantling site. Furthermore, we found that urinary concentrations of Σ10OH-PAHs and individual OH-PAHs were significantly associated with elevated 8-OHdG, in samples collected from e-waste dismantling site; the levels of urinary 1-hydroxypyrene (1-PYR) (r=0.284, p<0.01) was significantly positively associated with MDA. Our results indicate that the exposure to PAHs at the e-waste dismantling site may have an effect on oxidative damage to DNA among selected participants, but this needs to be validated in large studies.


Modulation of hepatocyte phenotype in vitro via chemomechanical tuning of polyelectrolyte multilayers.
It is increasingly appreciated that since cell and tissue functions are regulated by chemomechanical stimuli, precise control over such stimuli will improve the functionality of tissue models. However, due to the inherent difficulty in decoupling these cues as presented by extracellular materials, few studies have explored the independent modulation of biochemical and mechanical stimuli towards the manipulation of sustained cellular processes. Here, we demonstrate that both mechanical compliance and ligand presentation of synthetic, weak polyelectrolyte multilayers (PEMs) can be tuned independently to influence the adhesion and liver-specific functions of primary rat hepatocytes over extended in vitro culture (two weeks). These synthetic PEMs exhibited elastic moduli E ranging over 200kPa<E<142MPa, as much as one thousand-fold more compliant than tissue-culture polystyrene (E approximately 2.5GPa). The most compliant of these PEM substrata promoted hepatocyte adhesion and spheroidal morphology. Subsequent modification of PEMs with type I collagen and the proteoglycan decorin did not alter substrata compliance, but enhanced the retention of spheroids on surfaces and stabilized hepatic functions (albumin and urea secretion, CYP450 detoxification activity). Decorin exhibited unique compliance-mediated effects on hepatic functions, down-regulating the hepatocyte phenotype when presented on highly compliant substrata while up-regulating hepatocyte functions when presented on increasingly stiffer substrata. These results show that phenotypic functions of liver models can be modulated by leveraging synthetic polymers to study and optimize the interplay of biochemical and mechanical cues at the cell-material interface. More broadly, these results suggest an enabling approach for the systematic design of functional tissue models applied to drug screening, cell-based therapies and fundamental studies in development, physiology and disease.


Export of macroinvertebrate prey from tidal freshwater wetlands provides a significant energy subsidy for outmigrating juvenile salmon.
Tidal freshwater wetlands linking terrestrial, riverine, and saline habitats are critical areas for material processing and exchange. Once historically widespread, herbaceous marsh and forested tidal freshwater wetlands especially are now highly degraded worldwide. Additionally, quantitative assessments of hydrology and material exchange from these systems are lacking compared to lotic and estuarine (saltmarsh) habitats. Here we investigate macroinvertebrate and energy export from tidal marsh and forested wetlands and consider potential benefits from this ecological process to endangered Pacific salmon in a large tidal freshwater system, the Columbia River (USA). Macroinvertebrate (salmon prey) concentration, water velocity, and discharge were measured at several wetland habitat types (forested swamp, emergent marsh, and restored marsh). We used these data to compute prey flux and transport metrics. Then, applying literature values to calculate prey energy equivalents and juvenile salmon metabolic requirements, we estimated the potential energy subsidy available to juvenile salmon. Numerically, larval stages of aquatic insects were the predominant type of prey exported from the wetlands, with Diptera chironomid fly abundance exceeding other groups. Energetically, however, non-chironomid dipterans and hemipteran prey comprised most of energy transport due to their higher energetic content (energy density × mean weight). We determined the prey energy transported from the sampled tidal channels was sufficient to meet energetic needs of tens to thousands of juvenile salmon per day, depending on prey production and hydrography. The prey taxonomic composition differed among organisms exiting forested swamp, emergent marsh, and restored marsh habitats with corresponding differences in energy transport, but all habitat types supported similar numbers of juvenile salmon. We conclude that macroinvertebrate prey exported from varied tidal freshwater wetlands likely provide significant benefits to juvenile salmon over a larger ecological footprint than the wetland area would suggest.


Temporal sensitivities related to color theory.
Sensitivities of color-normal observers to temporal variations in stimulus luminance and chromaticity were measured for sine-wave stimuli between 1.5 and 20 Hz. Clear differences were found in observers' sensitivities to isochromatic luminance variations and to isoluminous chromaticity variations for wavelength pairs selected to test temporal discriminability along the red-green and yellow-blue dimensions, respectively. Despite interobserver differences in individual red-green functions, a given observer's sensitivity could be described by a single curve shape specific to that observer. Overall sensitivity for yellow-blue was less than that for red-green for all observers. Differences in curve shape between red-green and yellow-blue functions are found for individual observers, but group averages reveal that the differences are not systematic. Red-green temporal sensitivity is largely unaffected by adapting backgrounds in red-green equilibrium but is attenuated at low frequencies by nonequilibrium backgrounds of the same luminance. Isochromatic luminance sensitivity is largely independent of our adapting backgrounds, but heterochromatic luminance modulation functions undergo expected changes in form.


Serine-associated one-carbon metabolic reprogramming: a new anti-cancer therapeutic strategy.
Tumour metabolism is a major focus of cancer research, and metabolic reprogramming is an important feature of malignant tumours. Serine is an important non-essential amino acid, which is a main resource of one-carbon units in tumours. Cancer cells proliferate more than normal cells and require more serine for proliferation. The cancer-related genes that are involved in serine metabolism also show changes corresponding to metabolic alterations. Here, we reviewed the serine-associated one-carbon metabolism and its potential as a target for anti-tumour therapeutic strategies.


Trends and hotspots in familial hypercholesterolemia: A bibliometric systematic review from 2002 to 2022.
We visually assessed the research hotspots of familial hypercholesterolemia (FH) using bibliometrics and knowledge mapping in light of the research state and development trend of FH. We employed bibliometric tools, such as CiteSpace and the alluvial generator, to illustrate the scientific accomplishments on FH by extracting pertinent literature on FH from the Web of Science Core Collection database from January 1, 2002, to December 31, 2022. A total of 4402 papers in total were selected for study; 29.2% of all articles globally were from the USA, followed by the Netherlands and England. The University of Amsterdam, University of Oslo, and University of Western Australia are the 3 institutions with the most publications in this area. Gerald F. Watts, Raul D. Santos, and John J. P. Kastelein wrote the majority of the pieces that were published. The New England Journal of Medicine, Circulation, and Atherosclerosis were the journals with the greatest number of papers in this field. Prevalence and genetic analysis of FH, proprotein convertase subtilisin/kexin 9 inhibitors, and inclisiran are current research hotspots for the condition. Future research in this area will be focused on gene therapy. FH research has shown shows a trend of ascending followed by leveling off. The prevalence and diagnosis of FH, proprotein convertase subtilisin/kexin 9 inhibitors, inclisiran, and gene therapy are current research hotspots. This report may serve as a reference for current research trends.


Preconcentration of β-blockers using functionalized ordered mesoporous silica as sorbent for SPE and their determination in waters by chiral CE.
A method for simultaneous separation and determination of four enantiomeric pairs of β-blockers in waters by chiral CE has been developed. Off-line SPE was employed using functionalized ordered mesoporous silica as sorbent. Separation by CE was achieved using a BGE composed by methylated-β-CD (1.25% w/v) dissolved in a 50 mM phosphate buffer (pH 2.5) and 30°C, with good chiral resolution for all enantiomers. Mesoporous silica functionalized with octadecyl groups (denoted SBA15-C18) was prepared by a postsynthesis method and applied for the preconcentration of atenolol, propranolol, metoprolol, and pindolol enantiomers in waters by off-line SPE. Under optimized conditions, a preconcentration factor of 300 was achieved, employing 100 mg of SBA15-C18 as sorbent, with recoveries between 96 and 105% in tap water and good repeatability (% RSD = 7-11%, n = 6). Commercial C18 amorphous silica (ExtraBondR C18 ) was also tested as sorbent for SPE, but results revealed better extraction capacity with higher recoveries for the SBA15-C18 material. The analytical characteristics of the off-line SPE-chiral CE method were evaluated, showing good precision, linearity, and accuracy with method quantification limits between 5.3 and 13.7 μg/L for all enantiomers. The SBA15-C18 material allowed the extraction of four enantiomeric pairs of β-blockers spiked in tap water, river water, and ground water with recoveries between 58 and 105%.


Prostaglandin E2 confers protection against diabetic coronary atherosclerosis by stimulating M2 macrophage polarization via the activation of the CREB/BDNF/TrkB signaling pathway.
It has been documented that M2 macrophage polarization plays a suppressive role in atherosclerosis in diabetes mellitus (DM). In addition, prostaglandin E2 (PGE2) is implicated in the development of M2 macrophage polarization. Therefore, the study aimed to investigate the specific mechanism of PGE2 in M2 macrophage polarization in diabetic coronary atherosclerosis (DMAS). Initially, clinical samples were obtained and DMAS mouse model was established. The expression of BDNF was determined, and M1 and M2 macrophage polarizations were evaluated. Then, the levels of BDNF and PGE2 were modified in DMAS mice and the serum indicator, atherosclerotic plaque, lipid uptake by PBMCs, as well as M1 and M2 macrophage polarization were determined. Macrophages were isolated and the effects of PGE2 and the CREB/BDNF/TrkB signaling pathway on M2 macrophage polarization were explored. BDNF was downregulated and macrophages were differentiated into M1 in DMAS patients and mice. BDNF and PGE2 were observed to promote M2 macrophage polarization, where atherosclerotic plaque and lipid uptake by PBMCs were reduced, and DMAS was alleviated in mice. Overexpression of BDNF activated the CREB/BDNF/TrkB signaling pathway and stimulated M2 macrophage polarization in macrophages. PGE2 stimulated M2 macrophage polarization by inducing KLF4 via the activation of the CREB/BDNF/TrkB signaling pathway. This study demonstrates that PGE2 promotes M2 macrophage polarization by activating the CREB/BDNF/TrkB signaling pathway, thus alleviating DMAS.


Targeting of proteins derived from self-processing polyproteins containing multiple signal sequences.
The 18aa 2A self-cleaving oligopeptide from foot-and-mouth disease virus can be used for co-expression of multiple, discrete proteins from a single ORF. 2A mediates a co-translational cleavage at its own C-terminus and is proposed to manipulate the ribosome into skipping the synthesis of a specific peptide bond (producing a discontinuity in the peptide backbone), rather than being involved in proteolysis. To explore the utility of the system to target discrete processing products, self-processing polyproteins comprising fluorescent proteins flanking 2A were constructed, permutating both the type of signal sequence and the location within the polyprotein. A polyprotein comprising a protein bearing an N-terminal signal sequence, 2A, then a protein lacking any signal sequence, was constructed. Interestingly, both proteins were translocated into the endoplasmic reticulum. Despite the discontinuity in the peptide backbone, the mammalian ribosome:translocon complex did not disassemble--the second protein (lacking any signal) 'slipstreamed' through the translocon formed by the first (signal-bearing) protein. These polyprotein systems provide a novel method of targeting proteins to different subcellular sites by transfection with a plasmid encoding a single ORF. The inclusion of a fluorescent reporter enables visualisation of expression levels, whilst inclusion of a selectable marker enables stable cell-lines to be established rapidly.


In a prospective study in young people, associations between changes in smoking behavior and risk factors for cardiovascular disease were complex.
This study investigates how voluntary changes in tobacco consumption are related to changes in biological risk factors for cardiovascular disease in 21- to 36-year-old men and women. Data of the Amsterdam Growth and Health Longitudinal Study (AGAHLS) were used to study the association between voluntary changes in tobacco consumption and changes in biological risk factors for cardiovascular disease (CVD) during 4-6 years of follow-up in 165 men and 195 women aged 21-36 years. We used multiple linear regression analyses with corrections for age and changes in other lifestyles. In both sexes, we found trends for a reduction in blood pressure, high-density lipoprotein cholesterol (HDL-C), body weight, and waist-to-hip ratio (WHR) and a rise in the ratio between total serum cholesterol (TC) and HDL-C (TC/HDL-C) with increasing tobacco consumption. Opposite trends were found with reducing tobacco consumption. In women, body weight, WHR, and waist circumference reduced significantly and independently with increasing tobacco consumption and increased significantly with decreasing tobacco consumption. These results suggest that voluntary changes in tobacco consumption go together with both healthy and unhealthy changes in biological risk factors for CVD.


Amebic colitis presenting as acute inflammatory bowel disease. Case report.
A 41-year-old woman who had lived in the tropics for 23 years developed a clinical picture of inflammatory bowel disease 4 years after resettlement in Sweden. Search for ova and trophozoites in stools was negative. As medical treatment was unsuccessful, total colectomy was considered. Repeated colonic endoscopy with multiple biopsies initially failed to show amebiasis, but subsequently the trophozoites were identified in biopsies from the rectosigmoid mucosa. The diagnosis was serologically confirmed. Metronidazole treatment was rapidly and lastingly effective.


Modeling the effects of structure and dynamics of the nitroxide side chain on the ESR spectra of spin-labeled proteins.
In the companion paper (J. Phys. Chem. B 2006, 110, jp0629487), a study of the conformational dynamics of methanethiosulfonate spin probes linked at a surface-exposed alpha-helix has been presented. Here, on the basis of this analysis, X-band ESR spectra of these spin labels are simulated within the framework of the Stochastic Liouville equation (SLE) methodology. Slow reorientations of the whole protein are superimposed on fast chain motions, which have been identified with conformational jumps and fluctuations in the minima of the chain torsional potential. Fast chain motions are introduced in the SLE for the protein reorientations through partially averaged magnetic tensors and relaxation times calculated according to the motional narrowing theory. The 72R1 and 72R2 mutants of T4 lysozyme, which bear the spin label at a solvent-exposed helix site, have been taken as test systems. For the side chain of the R2 spin label, only a few noninterconverting conformers are possible, whose mobility is limited to torsional fluctuations, yielding almost identical spectra, typical of slightly mobile nitroxides. In the case of R1, more complex spectra result from the simultaneous presence of constrained and mobile chain conformers, with relative weights that can depend on the local environment. The model provides an explanation for the experimentally observed dependence of the spectral line shapes on temperature, solvent, and pattern of substituents in the pyrroline ring. The relatively simple methodology presented here allows the introduction of realistic features of the spin probe dynamics into the simulation of ESR spectra of spin-labeled proteins; moreover, it provides suggestions for a proper account of such dynamics in more sophisticated approaches.


Cryoextraction: A novel approach to remove aspirated chewing gum.
The extraction of aspirated foreign bodies can prove challenging at times, requiring even rigid bronchoscopy. Cryotherapy probes have been reported to help with extraction of foreign bodies. We present a case where successful "cryoextraction" was performed on an aspirated chewing gum. The case highlights the fact that this technique is useful to extract all materials that have water content. This technique can be performed through flexible bronchoscopy and can save patients from more aggressive approaches.


Synergistic inhibition of cancer cell proliferation with a combination of δ-tocotrienol and ferulic acid.
Rice bran consists of many functional compounds and thus much attention has been focused on the health benefits of its components. Here, we investigated the synergistic inhibitory effects of its components, particularly δ-tocotrienol (δ-T3) and ferulic acid (FA), against the proliferation of an array of cancer cells, including DU-145 (prostate cancer), MCF-7 (breast cancer), and PANC-1 (pancreatic cancer) cells. The combination of δ-T3 and FA markedly reduced cell proliferation relative to δ-T3 alone, and FA had no effect when used alone. Although δ-T3 induced G1 arrest by up-regulating p21 in PANC-1 cells, more cells accumulated in G1 phase with the combination of δ-T3 and FA. This synergistic effect was attributed to an increase in the cellular concentration of δ-T3 by FA. Our results suggest that the combination of δ-T3 and FA may present a new strategy for cancer prevention and therapy.


The Pro- and Anti-Inflammatory Cytokine Response to Exercise in Adolescent Swimmers.
Whether or not individuals with allergy and asthma experience different patterns of change in the balance of both pro- and anti-inflammatory mediators with acute exercise is not known. We hypothesized that adolescent swimmers with a clinical diagnosis of respiratory allergy would have an exaggerated proinflammatory response to laboratory exercise relative to a no-allergy comparison group. Adolescent swimmers (17 with clinical symptoms of respiratory allergy (CSRA) and 17 in comparison group) completed the American Thoracic Society (ATS) exercise challenge on cycle ergometer. Blood was collected at baseline and immediately post-exercise. All study tests were conducted at the Institute for Clinical Translational Science at the University of California, Irvine. Circulating cytokines, growth factors, and adhesion molecules were measured using ELISAs including transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, P-selectin, and immunoglobulin E (IgE). There was a trend toward higher resting levels of TNF-α in the CSRA group (P = 0.076). Exercise induced a significant increase in P-selectin and TGF-β1 in both groups. TNF-α increased significantly (17%) in the comparison group (pre = 0.6, post = 0.7 pg/mL), but not in the CSRA group. IL-6 increased significantly in the CSRA group (pre = 0.7, post = 0.8 pg/mL), but not in the comparison group. Circulating levels of IL-4 and IL-10 were not altered immediately post-exercise in either group. A short bout of intense exercise increased inflammatory growth factors and adhesion molecules, namely TGF-β1 and P-selectin, both of which are known to be involved in allergic airway diseases. Differences in resting IL-6 and TNF-α and exercise alterations in these cytokines may also contribute to allergic disease in adolescent elite swimmers.


Resveratrol as a therapeutic agent for Alzheimer's disease.
Alzheimer's disease (AD) is the most common cause of dementia, but there is no effective therapy till now. The pathogenic mechanisms of AD are considerably complex, including Aβ accumulation, tau protein phosphorylation, oxidative stress, and inflammation. Exactly, resveratrol, a polyphenol in red wine and many plants, is indicated to show the neuroprotective effect on mechanisms mostly above. Recent years, there are numerous researches about resveratrol acting on AD in many models, both in vitro and in vivo. However, the effects of resveratrol are limited by its pool bioavailability; therefore researchers have been trying a variety of methods to improve the efficiency. This review summarizes the recent studies in cell cultures and animal models, mainly discusses the molecular mechanisms of the neuroprotective effects of resveratrol, and thus investigates the therapeutic potential in AD.


Inspiratory work of breathing during spontaneous ventilation using demand valves and continuous flow systems.
To diminish the work of breathing, some demand valve systems are equipped with inspiratory pressure support (IPS). The purpose of this study was to evaluate the work performed during spontaneous breathing using the Siemens Servo 900C ventilator (SVC) at the minimal IPS level available, and comparing it with a demand valve ventilator without IPS, the Ohmeda CPU1 (CPU1), and with a home-built continuous flow system (CFS). We found a larger minute ventilation and inspiratory peak flow with the SVC and the CFS than with the CPU1 (p less than 0.05). When the work of breathing was measured at the airway opening, we found that the CFS led to the least amount of work (0.17 +/- 0.05 J.L-1, p less than 0.05). Additionally, this work was strikingly less for SVC than for CPU1 (0.22 +/- 0.06 versus 0.42 +/- 0.10 J.L-1, p less than 0.001) as a result of a higher flow supplied by the SVC. By contrast, the work measured using the esophageal pressure, i.e., including the work dissipated on the lung and airways, was significantly reduced with the CFS (1.34 +/- 0.45 J.L-1, p less than 0.05), but surprisingly not different between SVC and CPU1 (1.49 +/- 0.57 versus 1.54 +/- 0.51 J.L-1). We conclude that the absence of a demand valve in CFS involves the lowest work of breathing. Likewise, the high flow capability in SVC reduces the work necessary to overcome the circuit and demand valve resistances.(ABSTRACT TRUNCATED AT 250 WORDS)


[Vascular and tissue changes in brain contusion foci in the acute period of craniocerebral trauma with varying degrees of consciousness disorder].
The author presents a comparative analysis of vascular and tissue reactions in brain contusion foci in the acute period of a craniocerebral injury involving various degrees of consciousness disorders. These reactions were found to depend on the periods elapsed since the injury and the severity of consciousness disorders.


Apolipoprotein A-I Is a Prognosticator of Nasopharyngeal Carcinoma in the Era of Intensity-modulated Radiotherapy.
Background: In the era of intensity-modulated radiotherapy (IMRT), distant metastasis remains the major cause of death from nasopharyngeal carcinoma (NPC). This study aimed to evaluate the clinical value of pretreatment serum lipid profiles in predicting clinical outcome of NPC. Methodology / Principal Findings: A total of 1927 consecutive patients who had untreated NPC and completed radical IMRT between Jan. 2010 and Dec. 2011 were retrospectively reviewed. Pretreatment serum lipid indexes including total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-I (apoAI) and apolipoprotein B were analyzed for their association with survivals, together with the clinical features (age, sex, pathological type, anemia, chemotherapy sequence and Epstein-Barr virus deoxyribonucleic acid). Hazard ratio (HR) and 95% confidence interval (CI) were calculated for each independent prognosticator. After univariate and multivariate survival analysis, low apoAI level (< 1.125 mmol/L) appeared to predict poor 5-year overall survival (OS), disease-free survival (DFS) and distant-metastasis-free survival (DMFS).The HRs were 1.549 (95% CI, 1.137-2.109), 1.293 (95% CI, 1.047-1.597) and 1.288 (95% CI, 1.022-1.623), respectively. Subgroup survival analysis showed that the apoAI maintained predicting independence for OS, DFS and DMFS in patients with locally advanced NPC, even in those treated with concurrent chemoradiotherapy. Conclusions / Significance: NPC patient with low serum level of pretreatment apoAI might be at risk of distant metastasis. Treatment aiming to eradicate distant metastasis might improve survival of these patients.


Planarized and Twisted Intramolecular Charge Transfer: A Concept for Fluorophores Showing Two Independent Rotations in Excited State.
TICT (twisted intramolecular charge transfer) compounds are characterized by showing a rotation around a single bond in the excited state: starting from an almost planar geometry in the ground state, a twisted system is formed in the electronic excited state. The previously reported PLICT (planarized intramolecular charge transfer) compounds show inverse behavior: starting from a twisted geometry in the electronic ground state, a planarized system is formed in the excited state by rotation around a single bond. Here, a concept for planarized and twisted intramolecular charge transfer (PLATICT) states is presented which amalgamates both (TICT and PLICT) effects. Due to an intramolecular charge transfer, both a twisting around one single bond and a planarization around another one occurs. In sum, the PLATICT system shows two independent rotations around different axes in the excited state. By means of quantum chemical calculations (TD-cam-B3LYP and CC2) and experimental studies, it is demonstrated that N-aryl-substituted 1-aminoindoles are able to form photoinduced PLATICT states. In the fluorescence spectra of N-aryl-substituted 1-aminoindoles with a methoxycarbonyl or a cyano group as substituent in the aryl ring, very large Stokes shifts (ca. 18 000 cm-1 ; >250 nm) are observed. The two independent rotations in the excited state, the very large Stokes shifts and their easy availability starting from indoline, make them very attractive for use as optical switches and motors in various fields of chemistry.