Shape Memory Polyurethane with Porous Architectures for Potential Applications in Intracranial Aneurysm Treatment.
Conventional endovascular embolization of intracranial (or brain) aneurysms using helical detachable platinum coils can be time-consuming and occasionally requires retreatment due to incomplete coil packing. These shortcomings create a need for new biomedical devices and methods of achieving brain aneurysm occlusion. This paper presents a biocompatible and highly porous shape memory polymer (SMP) material with potential applications in the development of novel endovascular devices for treating complex intracranial aneurysms. The novel highly porous polyurethane SMP is synthesized as an open cell foam material with a glass transition temperature (Tg) of 39 °C using a sugar particle leaching method. Once heated above the Tg, the compressed SMP foam is able to quickly return to its original shape. An electrical resistance heating method is also employed to demonstrate a potential triggering design for the shape recovery process in future medical applications. The mechanical properties of the developed SMP foam are characterized at temperatures up to 10 °C above the respective Tg. The results from this work demonstrate that the porous SMP material developed in this study and the electrical resistance heating trigger mechanism provide a solid foundation for future design of biomedical devices to enhance the long-term therapeutic outcomes of endovascular intracranial aneurysm treatments.


Characterization of functional heme domains from soluble guanylate cyclase.
Soluble guanylate cyclase (sGC) is a heterodimeric, nitric oxide (NO)-sensing hemoprotein composed of two subunits, alpha1 and beta1. NO binds to the heme cofactor in the beta1 subunit, forming a five-coordinate NO complex that activates the enzyme several hundred-fold. In this paper, the heme domain has been localized to the N-terminal 194 residues of the beta1 subunit. This fragment represents the smallest construct of the beta1 subunit that retains the ligand-binding characteristics of the native enzyme, namely, tight affinity for NO and no observable binding of O(2). A functional heme domain from the rat beta2 subunit has been localized to the first 217 amino acids beta2(1-217). These proteins are approximately 40% identical to the rat beta1 heme domain and form five-coordinate, low-spin NO complexes and six-coordinate, low-spin CO complexes. Similar to sGC, these constructs have a weak Fe-His stretch [208 and 207 cm(-)(1) for beta1(1-194) and beta2(1-217), respectively]. beta2(1-217) forms a CO complex that is very similar to sGC and has a high nu(CO) stretching frequency at 1994 cm(-)(1). The autoxidation rate of beta1(1-194) was 0.073/min, while the beta2(1-217) was substantially more stable in the ferrous form with an autoxidation rate of 0.003/min at 37 degrees C. This paper has identified and characterized the minimum functional ligand-binding heme domain derived from sGC, providing key details toward a comprehensive characterization.


Effect of folinic acid on the capacity of trimethoprim-sulfamethoxazole to prevent and treat Pneumocystis carinii pneumonia in rats.
Daily administration of 1 mg of folinic acid to immunosuppressed rats with incipient or established Pneumocystis carinii pneumonia did not impair the capacity of trimethoprim-sulfamethoxazole to either prevent or treat this disease. These observations constitute the first experimental support for the use of folinic acid to prevent or control cytopenias that occur in patients with Pneumocystis carinii pneumonia who are under trimethoprim-sulfamethoxazole treatment.


High-Performance Flexible Photodetectors based on High-Quality Perovskite Thin Films by a Vapor-Solution Method.
Organometal halide perovskites are new light-harvesting materials for lightweight and flexible optoelectronic devices due to their excellent optoelectronic properties and low-temperature process capability. However, the preparation of high-quality perovskite films on flexible substrates has still been a great challenge to date. Here, a novel vapor-solution method is developed to achieve uniform and pinhole-free organometal halide perovskite films on flexible indium tin oxide/poly(ethylene terephthalate) substrates. Based on the as-prepared high-quality perovskite thin films, high-performance flexible photodetectors (PDs) are constructed, which display a nR value of 81 A W-1 at a low working voltage of 1 V, three orders higher than that of previously reported flexible perovskite thin-film PDs. In addition, these flexible PDs exhibit excellent flexural stability and durability under various bending situations with their optoelectronic performance well retained. This breakthrough on the growth of high-quality perovskite thin films opens up a new avenue to develop high-performance flexible optoelectronic devices.


Curriculum-Based Deep Reinforcement Learning for Quantum Control.
Deep reinforcement learning (DRL) has been recognized as an efficient technique to design optimal strategies for different complex systems without prior knowledge of the control landscape. To achieve a fast and precise control for quantum systems, we propose a novel DRL approach by constructing a curriculum consisting of a set of intermediate tasks defined by fidelity thresholds, where the tasks among a curriculum can be statically determined before the learning process or dynamically generated during the learning process. By transferring knowledge between two successive tasks and sequencing tasks according to their difficulties, the proposed curriculum-based DRL (CDRL) method enables the agent to focus on easy tasks in the early stage, then move onto difficult tasks, and eventually approaches the final task. Numerical comparison with the traditional methods [gradient method (GD), genetic algorithm (GA), and several other DRL methods] demonstrates that CDRL exhibits improved control performance for quantum systems and also provides an efficient way to identify optimal strategies with few control pulses.


Oral hygiene products and acidic medicines.
Acidic or EDTA-containing oral hygiene products and acidic medicines have the potential to soften dental hard tissues. The low pH of oral care products increases the chemical stability of some fluoride compounds, favors the incorporation of fluoride ions in the lattice of hydroxyapatite and the precipitation of calcium fluoride on the tooth surface. This layer has some protective effect against an erosive attack. However, when the pH is too low or when no fluoride is present these protecting effects are replaced by direct softening of the tooth surface. Xerostomia or oral dryness can occur as a consequence of medication such as tranquilizers, anti-histamines, anti-emetics and anti-parkinsonian medicaments or of salivary gland dysfunction e.g. due to radiotherapy of the oral cavity and the head and neck region. Above all, these patients should be aware of the potential demineralization effects of oral hygiene products with low pH and high titratable acids. Acetyl salicylic acid taken regularly in the form of multiple chewable tablets or in the form of headache powder as well chewing hydrochloric acids tablets for treatment of stomach disorders can cause erosion. There is most probably no direct association between asthmatic drugs and erosion on the population level. Consumers, patients and health professionals should be aware of the potential of tooth damage not only by oral hygiene products and salivary substitutes but also by chewable and effervescent tablets. Additionally, it can be assumed that patients suffering from xerostomia should be aware of the potential effects of oral hygiene products with low pH and high titratable acids.


Greater response to placebo in children than in adults: a systematic review and meta-analysis in drug-resistant partial epilepsy.
Despite guidelines establishing the need to perform comprehensive paediatric drug development programs, pivotal trials in children with epilepsy have been completed mostly in Phase IV as a postapproval replication of adult data. However, it has been shown that the treatment response in children can differ from that in adults. It has not been investigated whether differences in drug effect between adults and children might occur in the treatment of drug-resistant partial epilepsy, although such differences may have a substantial impact on the design and results of paediatric randomised controlled trials (RCTs). Three electronic databases were searched for RCTs investigating any antiepileptic drug (AED) in the add-on treatment of drug-resistant partial epilepsy in both children and adults. The treatment effect was compared between the two age groups using the ratio of the relative risk (RR) of the 50% responder rate between active AEDs treatment and placebo groups, as well as meta-regression. Differences in the response to placebo and to active treatment were searched using logistic regression. A comparable approach was used for analysing secondary endpoints, including seizure-free rate, total and adverse events-related withdrawal rates, and withdrawal rate for seizure aggravation. Five AEDs were evaluated in both adults and children with drug-resistant partial epilepsy in 32 RCTs. The treatment effect was significantly lower in children than in adults (RR ratio: 0.67 [95% confidence interval (CI) 0.51-0.89]; p = 0.02 by meta-regression). This difference was related to an age-dependent variation in the response to placebo, with a higher rate in children than in adults (19% versus 9.9%, p < 0.001), whereas no significant difference was observed in the response to active treatment (37.2% versus 30.4%, p = 0.364). The relative risk of the total withdrawal rate was also significantly lower in children than in adults (RR ratio: 0.65 [95% CI 0.43-0.98], p = 0.004 by metaregression), due to higher withdrawal rate for seizure aggravation in children (5.6%) than in adults (0.7%) receiving placebo (p < 0.001). Finally, there was no significant difference in the seizure-free rate between adult and paediatric studies. Children with drug-resistant partial epilepsy receiving placebo in double-blind RCTs demonstrated significantly greater 50% responder rate than adults, probably reflecting increased placebo and regression to the mean effects. Paediatric clinical trial designs should account for these age-dependent variations of the response to placebo to reduce the risk of an underestimated sample size that could result in falsely negative trials.


Editorial.
During its 128 years of operation, Psychological Review has exerted a powerful and consistent influence on the field under its long-term sponsor, the American Psychological Association (APA). Notwithstanding changes in ownership, it has always been what it is now-the flagship of the Association and the field. Since its inception, the journal has focused on theoretical analyses (e.g., systematic evaluations of alternative theories) and/or developments (e.g., the generation of novel theories) in the psychological sciences. Thus, the objectives of any incoming editor and editorial board remain steadfast: (a) to maintain and enhance the standing of Psychological Review in the field and (b) to correspondingly align its scope, content, and operations with any changes in the Association, the field of psychology in particular, and science and society in general. The journal's new senior editorial team is excited to navigate Psychological Review through the ever-changing landscape of psychology at this time of multiple challenges, referred to by the United Nations Secretary General António Guterres as "the greatest cascade of crises in our lifetime." Although we are initiating a number of changes, we will do our best to maintain Psychological Review's excellence. This will involve our capacity to reflect on and disseminate new theoretical developments, enriched and inspired by current trends in science in general and in psychological science in particular, while maintaining an overarching commitment to advancing the field through the incorporation of diverse perspectives. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


A quartz nanopillar hemocytometer for high-yield separation and counting of CD4(+) T lymphocytes.
We report the development of a novel quartz nanopillar (QNP) array cell separation system capable of selectively capturing and isolating a single cell population including primary CD4(+) T lymphocytes from the whole pool of splenocytes. Integrated with a photolithographically patterned hemocytometer structure, the streptavidin (STR)-functionalized-QNP (STR-QNP) arrays allow for direct quantitation of captured cells using high content imaging. This technology exhibits an excellent separation yield (efficiency) of ~95.3 ± 1.1% for the CD4(+) T lymphocytes from the mouse splenocyte suspensions and good linear response for quantitating captured CD4(+) T-lymphoblasts, which is comparable to flow cytometry and outperforms any non-nanostructured surface capture techniques, i.e. cell panning. This nanopillar hemocytometer represents a simple, yet efficient cell capture and counting technology and may find immediate applications for diagnosis and immune monitoring in the point-of-care setting.


Designing a Novel Monolayer β-CSe for High Performance Photovoltaic Device: An Isoelectronic Counterpart of Blue Phosphorene.
Using the first-principles method, an unmanufactured structure of blue-phosphorus-like monolayer CSe (β-CSe) was predicted to be stable. Slightly anisotropic mechanical characteristics in β-CSe sheet were discovered: it can endure an ultimate stress of 5.6 N/m at 0.1 along an armchair direction, and 5.9 N/m at 0.14 along a zigzag direction. A strain-sensitive transport direction was found in β-CSe, since β-CSe, as an isoelectronic counterpart of blue phosphorene (β-P), also possesses a wide indirect bandgap that is sensitive to the in-plane strain, and its carrier effective mass is strain-dependent. Its indirect bandgap character is robust, except that armchair-dominant strain can drive the indirect-direct transition. We designed a heterojunction by the β-CSe sheet covering α-CSe sheet. The band alignment of the α-CSe/β-CSe interface is a type-II van der Waals p-n heterojunction. An appreciable built-in electric field across the interface, which is caused by the charges transfering from β-CSe slab to α-CSe, renders energy bands bending, and it makes photo-generated carriers spatially well-separated. Accordingly, as a metal-free photocatalyst, α-CSe/β-CSe heterojunction was endued an enhanced solar-driven redox ability for photocatalytic water splitting via lessening the electron-hole-pair recombination. This study provides a fundamental insight regarding the designing of the novel structural phase for high-performance light-emitting devices, and it bodes well for application in photocatalysis.


Proton conductivity of imidazole entrapped in microporous molecular sieves.
Imidazole embedded in molecular sieves shows remarkable and steady proton conductivity (>1 × 10-5 S cm-1 above 360 K). It can be considered to be a promising solid high proton conducting electrolyte for fuel cells. The conductivity depends on imidazole loading and mobility, which result from the pore geometry, the chemical nature of matrices and the preparation method.


Dispersant Effects on Single-Walled Carbon Nanotube Antibacterial Activity.
There is significant interest in understanding whether nanomaterials with outstanding mechanical or electrical properties also possess antibacterial properties. However, assessment of antibacterial activity is a complex problem at the interface of chemistry and microbiology. Results can be affected by many factors including nanomaterial size, surface chemistry, concentration, and the dispersion media. The difficulty of dispersing nanomaterials such as single-walled carbon nanotubes (SWNTs) has resulted in many studies being conducted in the presence of dispersion aides which may themselves contribute to bacterial stress. The recent discovery that a standard microbial growth media, tryptic soy broth (TSB), is an effective SWNT dispersant provides a new opportunity to investigate the potential antibacterial activity of SWNTs using dispersants that range from antibacterial to growth-supporting. The five dispersants chosen for this work were Sodium dodecyl sulfate (SDS), pluronic, lysozyme, DNA, and tryptic soy broth. Staphylococcus aureus and Salmonella enterica were used as the model Gram-positive and Gram-negative bacteria. Activity was measured in terms of colony forming unit (CFU) and optical density measurements. None of the systems exhibited activity against Salmonella. SDS was fatal to Staph. aureus regardless of the presence of SWNTs. The activity of pluronic and lysozyme against Staph. aureus was enhanced by the presence of SWNTs. In contrast, the DNA and TSB dispersions did not have any activity regardless of the presence of SWNTs. These results highlight that the purported antibacterial activity of SWNTs may only be effective against bacteria that are sensitized by the dispersant and suggests the need for additional research on the mechanisms by which SWNT-dispersant interactions can result in antibacterial activity.


A multiplexed FRET aptasensor for the simultaneous detection of mycotoxins with magnetically controlled graphene oxide/Fe3O4 as a single energy acceptor.
Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are the most common mycotoxins and often coexist in agricultural products, and are known to form a toxic superposition and even have carcinogenic effects on humans. We propose a multiplexed fluorescence resonance energy transfer (FRET) aptasensor for the simultaneous detection of mycotoxins with magnetically controlled graphene oxide (GO)/Fe3O4 as the single energy acceptor. CdTe quantum dots emitting green (GQDs) and red (RQDs) fluorescence were modified by aptamers that are specific for AFB1 and FB1 and used as dual energy donors. Compared with conventional FRET systems based on a GO quencher, GO/Fe3O4, as a single energy acceptor, not only simultaneously quenches the different fluorescence emission peaks of the aptamer-modified GQDs and RQDs but also can be effectively removed by magnetic separation to eliminate background interference. In the absence of the GO/Fe3O4 nanocomposites, the aptamer-modified GQDs and RQDs emit strong fluorescence under ultraviolet radiation. The fluorescence of the GQDs and RQDs is quenched when the GO/Fe3O4 nanocomposites are added to the system owing to the π-π stacking interactions between the GO/Fe3O4 nanocomposites and the GQD- and RQD-labeled aptamers. However, in the presence of AFB1 and FB1, the binding of aptamers to their specific targets will fold their single stranded structures and hinder the contact between the base group in the aptamers and GO/Fe3O4, which will cause the fluorescence recovery of GQDs and RQDs. With the help of a one-step magnetic separation, the supernatants can be collected for fluorescence analysis. After the optimization of detection conditions, the developed method had a wide linear range of 10 pg mL-1-100 ng mL-1 for AFB1 and 50 pg mL-1-300 ng mL-1 for FB1 and showed no cross-reactivity with other closely related mycotoxins. The limit of detection for AFB1 and FB1 were calculated to be 6.7 and 16.2 pg mL-1 based on S/N = 3, respectively. The detection of mycotoxins was successfully realized in peanut samples, indicating the successful application of this new FRET system for various future targets.


Development of Causative Treatment Strategies for Lacrimal Gland Insufficiency by Tissue Engineering and Cell Therapy. Part 1: Regeneration of Lacrimal Gland Tissue: Can We Stimulate Lacrimal Gland Renewal In Vivo?
Severe dry eye syndrome (DES) is a complex disease that is commonly caused by inflammatory and degenerative changes in the lacrimal gland, and can result in severe pain and disruption to visual acuity. In healthy subjects, the ocular surface is continually lubricated by the tear film that ensures that the ocular surface remains moist and free of debris, enabling normal vision. The lacrimal fluid, mid-layer of the tear film, is mainly produced by the lacrimal gland and if this is dysfunctional for any reason, severe DES can develop. Currently, only palliative treatments for DES exist that aim to either replace or retain tears and/or minimize inflammation. A curative approach that aims to trigger the regeneration of existing lacrimal gland tissue in situ may, therefore, be very beneficial to DES patients. This article reviews the different approaches that have been explored toward lacrimal gland regeneration. Progress to date in vitro, in vivo, and in man is described with a focus on clinical feasibility and efficacy. Promising candidates for drug-dependent treatment of DES are growth factors and cytokines, such as hepatocyte growth factor (HGF) and tumor necrosis factor α-stimulated gene 6 protein (TSG-6). Only a few studies have evaluated gene therapy for lacrimal gland deficiencies, but with promising results. However gene therapy carries a variety of risks regarding carcinogenesis and therefore a treatment in the near future using this approach seems to be unlikely. Cell therapies utilizing mesenchymal stem cells (MSCs) seem to be more applicable than those using human amniotic membrane (hAM) epithelial cells or induced pluripotent stem (iPS) cells, since MSCs combine the favorable traits of both (multipotency, capability to stimulate regeneration immunomodulatory and non-immunogenic properties).


The gradient in health inequalities among families and children: a review of evaluation frameworks.
Public health policies and interventions that seek to tackle the social gradient in health need to be more adequately evaluated. The GRADIENT Project sets out to recommend public health policy options which effectively tackle health inequalities and address the gradient in health determinants among families and children in Europe. This work is underpinned by the development of a dedicated evaluation framework-a scheme that elaborates steps in a process of assessment which can act as a useful guide for decision makers. This paper presents the results from a narrative review, based on realist review principles, of 34 evaluation frameworks. It uses a set of analytical criteria, drawn from the EUHPID health development model, the Ottawa Charter for Health Promotion, and the wider literature on health inequalities, to analyse these frameworks. The findings reveal that no one suitable evaluation framework exists to evaluate whether policies and/or interventions targeting children and families reduce the health gradient. It is suggested that this work will be useful in assessing the complex nature of public health interventions and their evaluation. It will be used to develop an evaluation framework to guide decision makers to begin to understand the key drivers at each stage of the policy development and implementation cycle.


Unsaturated Polyester Resin Nanocomposites Containing ZnO Modified with Oleic Acid Activated by N,N'-Carbonyldiimidazole.
Hydrophobic zinc oxide (ZnO) nanoparticles were produced through grafting aminopropyltriethoxysilane (APS) and oleic acid (OA), which was activated by N,N'-carbonyldiimidazole (CDI). The functional group containing ZnO nanoparticles were incorporated into unsaturated polyester (UP) resin, and their dispersibility in the UP matrix and effects on the properties of UP/ZnO nanocomposites were investigated. ZnO nanoparticles modified by APS and OA activated by CDI, (CDI⁻OA⁻APS⁻ZnO), can be homogeneously dispersed as supported by transmission electron microscopy (TEM) investigations and had been encapsulated in the UP resin. CDI⁻OA⁻APS⁻ZnO nanoparticles were embedded in the net structure of the UP composites through chemical bonds between oleic acid, styrene, and polyester resin, which significantly influence the cure reaction of UP resin and the properties of UP composites. Thermogravimetric analysis (TGA) results show that the incorporation of ZnO nanoparticles could improve the thermal stability of UP when thermal cracking temperature exceeds 365 °C. The exothermic peak and the initial temperature of cure reaction of the UP resin decreased with increasing ZnO content. The tensile strength and bending strength of UP/CDI⁻OA⁻APS⁻ZnO nanocomposites increased by 91.4% and 71.3% when 3 wt % CDI⁻OA⁻APS⁻ZnO nanoparticles was added into the composites, respectively, compared with pure UP resin.


Automated Localization of Focal Ventricular Tachycardia From Simulated Implanted Device Electrograms: A Combined Physics-AI Approach.
Background: Focal ventricular tachycardia (VT) is a life-threating arrhythmia, responsible for high morbidity rates and sudden cardiac death (SCD). Radiofrequency ablation is the only curative therapy against incessant VT; however, its success is dependent on accurate localization of its source, which is highly invasive and time-consuming. Objective: The goal of our study is, as a proof of concept, to demonstrate the possibility of utilizing electrogram (EGM) recordings from cardiac implantable electronic devices (CIEDs). To achieve this, we utilize fast and accurate whole torso electrophysiological (EP) simulations in conjunction with convolutional neural networks (CNNs) to automate the localization of focal VTs using simulated EGMs. Materials and Methods: A highly detailed 3D torso model was used to simulate ∼4000 focal VTs, evenly distributed across the left ventricle (LV), utilizing a rapid reaction-eikonal environment. Solutions were subsequently combined with lead field computations on the torso to derive accurate electrocardiograms (ECGs) and EGM traces, which were used as inputs to CNNs to localize focal sources. We compared the localization performance of a previously developed CNN architecture (Cartesian probability-based) with our novel CNN algorithm utilizing universal ventricular coordinates (UVCs). Results: Implanted device EGMs successfully localized VT sources with localization error (8.74 mm) comparable to ECG-based localization (6.69 mm). Our novel UVC CNN architecture outperformed the existing Cartesian probability-based algorithm (errors = 4.06 mm and 8.07 mm for ECGs and EGMs, respectively). Overall, localization was relatively insensitive to noise and changes in body compositions; however, displacements in ECG electrodes and CIED leads caused performance to decrease (errors 16-25 mm). Conclusion: EGM recordings from implanted devices may be used to successfully, and robustly, localize focal VT sources, and aid ablation planning.


The environmental roots of non-communicable diseases (NCDs) and the epigenetic impacts of globalization.
Non-communicable diseases (NCDs) are increasing worldwide. We hypothesize that environmental factors (including social adversity, diet, lack of physical activity and pollution) can become "embedded" in the biology of humans. We also hypothesize that the "embedding" partly occurs because of epigenetic changes, i.e., durable changes in gene expression patterns. Our concern is that once such factors have a foundation in human biology, they can affect human health (including NCDs) over a long period of time and across generations. To analyze how worldwide changes in movements of goods, persons and lifestyles (globalization) may affect the "epigenetic landscape" of populations and through this have an impact on NCDs. We provide examples of such changes and effects by discussing the potential epigenetic impact of socio-economic status, migration, and diet, as well as the impact of environmental factors influencing trends in age at puberty. The study of durable changes in epigenetic patterns has the potential to influence policy and practice; for example, by enabling stratification of populations into those who could particularly benefit from early interventions to prevent NCDs, or by demonstrating mechanisms through which environmental factors influence disease risk, thus providing compelling evidence for policy makers, companies and the civil society at large. The current debate on the '25 × 25 strategy', a goal of 25% reduction in relative mortality from NCDs by 2025, makes the proposed approach even more timely. Epigenetic modifications related to globalization may crucially contribute to explain current and future patterns of NCDs, and thus deserve attention from environmental researchers, public health experts, policy makers, and concerned citizens.


About difference electron densities and their properties.
Difference electron densities do not play a central role in modern phase refinement approaches, essentially because of the explosive success of the EDM (electron-density modification) techniques, mainly based on observed electron-density syntheses. Difference densities however have been recently rediscovered in connection with the VLD (Vive la Difference) approach, because they are a strong support for strengthening EDM approaches and for ab initio crystal structure solution. In this paper the properties of the most documented difference electron densities, here denoted as F - Fp, mF - Fp and mF - DFp syntheses, are studied. In addition, a fourth new difference synthesis, here denoted as {\overline F_q} synthesis, is proposed. It comes from the study of the same joint probability distribution function from which the VLD approach arose. The properties of the {\overline F_q} syntheses are studied and compared with those of the other three syntheses. The results suggest that the {\overline F_q} difference may be a useful tool for making modern phase refinement procedures more efficient.


No easy answers.
Illegal immigration is on the rise and Congress has restricted access to health coverage for legal immigrants. Those factors combine to create a large pool of uninsured patients, and hospitals once again are left to foot the bill--to the tune of millions of dollars a year. And the problem is no longer restricted to border states and big cities.


Valuing difference: caregiving by mothers of children with disabilities.
Mothers who are caregivers of children with disabilities seek to have their children accepted and valued by others in society. This is supported by many reports of studies from different countries that involved mothers of children with disabilities, as well as through publications by disability advocates. In this paper, qualitative research data from interviews with seven mothers of children with disabilities were reanalysed using Bourdieu's theory of practice and van Manen's phenomenological methodology. The results showed that these mothers, who were caregivers of children with disabilities, valued their children despite ongoing challenges, and wanted others to do likewise. This study supports the importance of valuing difference in terms of the insights and understanding gained from those with disabilities and their caregivers. It would be difficult to replicate it exactly; its relevance lies in demonstrating that valuable insights can be gained from extending reflective practice to research that involves re-examining a study from a different theoretical perspective.


Soyasaponin I, a potent and specific sialyltransferase inhibitor.
A growing number of reports demonstrate that hypersialylation, which is observed in certain pathological processes, such as oncogenic transformation, tumor metastasis, and invasion, is associated with enhanced sialyltransferase (ST) activity. There is therefore a need for the development of ST inhibitors to modulate ST activity and thus alleviate the disease processes caused by STs. In the present study, soyasaponin I had been discovered to be a potent and specific ST inhibitor by screening strategy from 7500 samples including micribial extracts and natural products. Kinetic analysis shows that it is a CMP-Neu5Ac competitive inhibitor with for ST3Gal I with an inhibition constant (K(i)) of 2.1 microM. In addition, it is only active against ST, but not against the other tested glycosyltransferases and glycosidases. Our study is the first report to discover ST inhibitor by screening method and also to provide the new chemical structure information that should be useful in the development of other novel ST inhibitors.


Effect of ovariectomy, hypophysectomy and/or GnRH analog (HRF) administration on the cell proliferation of the MXT mouse hormone-dependent mammary tumor.
The MXT tumor is an experimental mammary neoplasm which is maintained by serial transplantation using B6D2F1 mice, and which contains significant amounts of estrogen and progesterone receptors. The aim of the present study is to examine the effects of ovariectomy (OVX) or ovariectomy plus hypophysectomy (OVX-HX) on both the macroscopic growth and the cell proliferation of this tumor. This cell proliferation was evaluated by means of in vivo tritiated thymidine autoradiography. In addition, we investigated the effects of a GnRH analog (Gonadorelin: HRF, 5-oxo-Pro-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-hydrochloride) on MTX tumor cell proliferation on 7 day-OVX and 5 day-HX (OVX-HX) mice. The uterine luminal epithelium was chosen to monitor the methodology. Our data clearly demonstrate that there is a delay in the growth of MXT tumors grafted into hypophysectomized animals and, to a lesser degree, ovariectomized animals. With respect to proliferation, castration induced a dramatic decrease of the thymidine labelling index (TLI) in the tissue used to monitor the methodology (the uterine luminal epithemium); in contrast, no cell proliferation was induced by hypophysectomy or HRF administration. In 4-week-old MXT tumors, ovariectomy also markedly decreased the TLI within a few days of its taking place. However hypophysectomy, performed on castrated animals, induced a significant and transient increase of cell proliferation in this neoplasm, an increase which lasted from the 2nd to the 5th day following the operation. The high basal level of MXT cell proliferation recorded in OVX-HX animals decreased dramatically after the administration of HRF between 12 and 48 h prior to the sacrifice of the animals. It is concluded that the HRF exerts a direct effect on the MXT tumor cells, and this HRF might be essential for their growth.


[Inequalities in the conditions of infection control in dentistry offices in a southeastern Brazilian city].
The study analyzed infection control conditions in dentistry offices in Cariacica, Espírito Santo, Brazil. Data pertaining to interviewees, location and type of office, setting, equipment, and materials were obtained by direct observation in all the registered services and in twenty unlicensed establishments operated by "non-graduate dentists". For grouped analysis of infection control measurements in each establishment, a composite indicator based on 19 variables was developed, such that the lower its value, the better the infection control. The results referred to 113 offices. Infection control in offices of "non-graduate dentists" (xICI = 23.05, dp = 11.86) was four times worse than for private offices. Public dental care services (xICI = 16.27; dp = 6.96) occupied an intermediate position. Conditions were also four times worse in dentistry offices located in peripheral urban areas. There was a clear-cut division in sanitary conditions within dental care as a whole. A large proportion of the population depending on dental care from unlicensed dentists is exposed to increased risk of cross-infection.


Fatal hepatic and renal toxicity as a complication of trabectedin therapy for radiation-induced sarcoma.
Trabectedin therapy was prescribed for a patient with radiation-induced sarcoma. Two doses of trabectedin were given before therapy was discontinued with the patient experiencing renal and liver failure. Despite discontinuing trabectedin the patient continued to experience increases in liver transaminases, bilirubin, blood urea nitrogen, and serum creatinine. Hemodialysis was initiated with no improvement. With all other causes being ruled out, trabectedin likely caused hepatic and renal failure leading to death in this patient. Recent literature suggests that patients may benefit from prophylactic dexamethasone as a means of reducing hepatic toxicity.


Phytoplankton Composition and Their Related Factors in Five Different Lakes in China: Implications for Lake Management.
In this paper, two trophic lakes: Lake Taihu and Lake Yanghe, and three alpine lakes: Lake Qinghai, Lake Keluke, and Lake Tuosu, were investigated to discover the connections between environmental factors and the phytoplankton community in lakes with differences in trophic levels and climatic conditions. Three seasonal data, including water quality and phytoplankton, were collected from the five lakes. The results demonstrated clear differences in water parameters and phytoplankton compositions in different lakes. The phytoplankton was dominated by Bacillariophyta, followed by Cyanobacteria and Chlorophyta in Lake Qinghai, Lake Keluke, and Lake Tuosu. It was dominated by Cyanobacteria (followed by Chlorophyta and Bacillariophyta in Lake Yanghe) and Cyanobacteria (followed by Chlorophyta and Cryptophyta in Lake Taihu). The temperature was an essential factor favoring the growth of Cyanobacteria, Chlorophyta, and Bacillariophyta, especially Cyanobacteria and Chlorophyta. The pH had significantly negative relationships with Cyanobacteria, Chlorophyta, and Bacillariophyta. Particularly, a high pH might be a strong and negative factor for phytoplankton growth in alpine lakes. A high salinity was also an adverse factor for phytoplankton. Those results could provide fundamental information about the phytoplankton community and their correlated factors in the alpine lakes of the Tibetan Plateau, contributing to the protection and management of alpine lakes.


p39R861-4, A Type 2 A/C2 Plasmid Carrying a Segment from the A/C1 Plasmid RA1.
The largest plasmid in the strain 39R861, which is used as a plasmid size standard, was recovered by conjugation and sequenced to determine its exact size. Plasmid p39R861-4 transferred at high frequency. Although reported to be the A/C1 plasmid RA1, p39R861-4 is a 155794-bp Type 2 A/C2 plasmid, in which a 39-kb segment, derived from RA1 that includes a relative of the RA1 resistance island, replaces 26.5 kb of the Type 2 backbone. p39R861-4 includes a single copy of IS10 and two resistance islands with a CR2-sul2 region in each of them. The 84 kb of backbone between the resistance islands is inverted relative to other known A/C plasmids and this inversion has arisen through recombination between the CR2-sul2 regions that are inversely oriented. The two resistance islands present before this inversion occurred were one related to but longer than that found in RA1, and one that is a form of the ARI-B island and identical to ARI-B in the A/C2 plasmid R55. They contain genes conferring resistance to tetracycline (tetA(D)), sulfonamides (sul2), and florfenicol and chloramphenicol (floR). The tet(D) determinant is flanked by two IS26 in a transposon-like structure named Tntet(D). Both resistance islands contain remnants of the two ends of the integrative element GIsul2, consistent with the sul2 gene being mobilized by GIsul2 rather than by CR2.


Early ostial vein graft stenosis: management by atherectomy.
During the initial perioperative period (1 mo to 1 yr) after saphenous vein coronary grafting, early stenosis and occlusion occurs in 5-8% of grafts due to intimal hyperplasia. We report a patient who developed ostial stenosis within 4 mo of bypass surgery at the aortotomy site of two vein grafts. Balloon angioplasty of the elastic stenoses did not provide significant luminal enlargement, but successful treatment of the lesions was obtained using directional atherectomy. Histological examination demonstrated intimal hyperplasia. Directional atherectomy may be an excellent technique for treatment of elastic ostial vein graft stenoses in lieu of conventional balloon dilatation.


Intrinsic competition and competitor-free-space influence the coexistence of parasitoids (Hymenoptera: Braconidae: Opiinae) of Neotropical Tephritidae (Diptera).
Endoparasitoid larvae may eliminate heterospecific competitors by physical or physiological means. The outcomes of these intrinsic competitions are often predictable with one species typically eliminating the other. The opiine braconids Doryctobracon areolatus (Szepligeti) and Utetes anastrephae (Viereck) are among the most common native parasitoids of frugivorous Tephritidae in the Neotropics and subtropics. U. anastrephae is typically the victor in intrinsic interactions with D. areolatus, but the later has a longer ovipositor and may find a competitor-free-space in larger fruit whose hosts are beyond the reach of U. anastrephae. An Asian opiine species, Diachasmimorpha longicaudata (Ashmead) has been introduced throughout much of the Americas. Its ovipositor is longer than that of D. areolatus and if it is a superior intrinsic competitor it should be able to cause local extinctions of D. areolatus. The outcomes of sequential ovipositions by D. longicaudata and D. areolatus and U. anastrephae found that D. longicaudata significantly suppresses development of D. areolatus. However, competitions between D. longicaudata and U. anastrephae were more equal. The denial of competitor free space may account for the gradual replacement of D. areolatus by D. longicaudata in Florida where both species were introduced ~40 yr ago. Diachasmimorpha longicaudata and D. areolatus continue to coexist in Mexico and this could be because of greater abiotic and biotic environmental complexity that allows for separate niches. Establishment or augmentative releases of D. longicaudata could result in elimination of native parasitoids and this should be considered before its introduction.


Boc5, a non-peptidic glucagon-like Peptide-1 receptor agonist, invokes sustained glycemic control and weight loss in diabetic mice.
Our recent discovery of the substituted cyclobutane Boc5, one of the first non-peptidic agonists at glucagon-like peptide-1 receptors, offers the potential of combining oral availability with full agonism capable of eliciting antidiabetic and antiobesity effects. The present study was aimed at determining the in vivo pharmacologic properties of Boc5 in both normal and diabetic mice following chronic administration, with emphasis on glycemic control and weight loss. C57BL/6J and db/db mice were treated daily with Boc5 for 4 weeks and a range of pharmacologic parameters, including hemoglobin A1c, intraperitoneal glucose tolerance, insulin tolerance, fasting insulin and leptin levels, food intake, body weight and fat mass, were assessed before and after the treatment. Effects on food intake, gastric emptying, and insulinogenic index were also investigated in animals acutely administered with Boc5. Boc5 (3 mg) was able to induce a durable restoration of glycemic control (normalization of both hemoglobin A1c and intraperitoneal glucose tolerance) in db/db mice, following 4 weeks of daily administration. As with peptidic glucagon-like peptide-1 receptor agonists, its glycemic benefit and weight (fat) loss were associated with dose-dependent effects that included reduction in food intake, slowing of gastric emptying (both of which reduce nutrient-drive at beta-cells), stimulation of insulin secretion (which was glucose-dependent), and elevation in insulin sensitivity. There was little effect on normal mice treated in the same manner. Our findings suggest that Boc5 is the only non-peptidic molecule reported thus far to simultaneously activate this spectrum of antidiabetic effects.


[Improvement of Medical Alarm Management Accuracy for Critical Care Nurses in a Continuous Renal Replacement Therapy Unit].
Continuous renal replacement therapy (CRRT) is a common medical treatment for critically ill patients. The alarm management component of CRRT is urgent and time sensitive. Patient safety and survival rates are jeopardized if critical care nurses do not handle this situation properly. However, clinical settings cannot provide nurses with the opportunity to practice alarm management, which results in related training difficulties. Based on a survey conducted in May 2018, the rate of proper alarm management for the nurses in our CRRT unit was only 53.1%. An investigation attributed this low rate to inadequacies in standard procedures, resources for reference, opportunities for hands-on experience, professional training at different levels, immediate assistance from industry, and lack of familiarity with the purpose and handling of alarm incidents. These findings motivated our project team to improve alarm management. To increase the accuracy of alarm management in CRRT critical care nurses to more than 90%. This project, which was implemented from September 8th, 2018 to August 31st, 2019, adopted a diverse and effective teaching strategy that included establishing standard procedures and technical tests; creating a plan for a case scenario simulation course using flipped teaching; providing scenario simulation videos; and designing online scenario simulation interactive exercises, nursing manuals, and flashcards of simplified procedures. The accuracy rate of proper alarm management for CCRT critical care nurses increased from 53.1% to 98.9%. Diverse teaching strategies may be used to effectively enhance the care provided by critical care nurses, increase patient safety, and improve the quality of care. The findings and strategies in this study may also be applied to other intensive care units.


Differences in cerebral asymmetries related to drinking history and ethnicity. A computerized axial tomography (CAT) scan study.
Normal computerized axial tomography scans of 179 American Indian, black, and white subjects were examined for cerebral asymmetry patterns. Information concerning the drinking history of each subject was also obtained. Results indicated that alcohol use history was associated with differences in asymmetry patterns, above and beyond differences associated with ethnicity. In subjects without a history of alcohol use, more whites were more likely to have left asymmetry of both occipital length and width, as compared to American Indians and blacks. In subjects with a history of alcohol use, all subjects closely resembled one another, regardless of ethnicity. In the total sample, alcohol users were more likely to show greater right occipital width.


An assessment of standardisation of HbA1c testing across clinical laboratories in India and its impact on diabetes management.
This study is aimed at evaluating the degree of standardisation of HbA1c and glucose testing across accredited laboratories in India. The information declared on the scope of testing by 147 medical laboratories accredited by the National Accreditation Board for Testing and Calibration Laboratories (NABL) across India was used by the authors for this study (http://www.nabl-india.org). This information on the scope of testing is available within the public domain and is accessible through the NABL website and covered laboratories accredited between 2009 and 2012. We focussed on HbA1c and glucose tests offered by laboratories and documented the way tests were named, the methodologies used and the degree of confidence in testing based on the coefficient of variation (CV). The data was independently reviewed by two medical biochemists and then subjected to analysis. Although the glucose test appeared to be ubiquitous, HbA1c assays appeared on the scope of testing in 87.1% of the laboratories. The HbA1c tests however appear to be poorly standardised across laboratories. We noted gross differences in test nomenclature, methodology and analytical performance across laboratories. This is one of the first studies that has focussed on the standards of laboratory care for diabetes management in India. The study highlights the lack of standardisation in nomenclature, analytical performance and methodology of tests used for HbA1c in NABL accredited laboratories across India. Affirmative actions in terms of improved regulation, patient advocacy, further studies on impact of laboratory quality and education of physicians, healthcare providers, laboratorians may improve harmonisation and quality of patient care in diabetes in India.


[Virtual bronchoscope system].
In this article, we describe the features of Virtual Bronchoscope System(VBS) and its practical use. VBS is constructed based on 3-D chest CT images. The bronchus region is automatically extracted from 3-D chest CT images by a three-dimensional region growing method. The surface rendering is employed for construction of virtualized tracheo-bronchial tree. It gives us an environment where we can observe inside the bronchi from an arbitrary viewpoint and a view direction. By mouse operation, the user can control the viewpoint and the view direction to fly through inside the airway in real time. VBS is applicable for a variety of purposes such as diagnosis, surgical planning, informed consent, education and training. One of extension of this system is a teaching tool for medical students. In the module for educational use, we have developed four functions for using the system as a teaching tool as follows: (a) automated display of bronchial anatomical names, (b) presenting questions about the currently observed branch in the endoscopic view, (c) display of the path which the user should follow, and (d) display of a question about the location of the artificially created tumor in the bronchus. These functions use the processed results of automated anatomical labeling. The method proposed here combines the knowledge based processing technique 'automated labeling of bronchial branch' and the novel visualization technique 'virtual bronchoscope'. This is one of new teaching tools of medical images. We conclude that this virtual bronchoscope system might have an important role in the medial students' education.


The potential impact of vaccination on the prevalence of gonorrhea.
Gonorrhea, one of the most common sexually transmitted infections worldwide, can lead to serious sequelae, including infertility and increased HIV transmission. Recently, untreatable, multidrug-resistant Neisseria gonorrhoeae strains have been reported. In the absence of new antibiotics, and given the speed with which resistance has emerged to all previously used antibiotics, development of a vaccine would be the ideal solution to this public health emergency. Understanding the desired characteristics, target population, and expected impact of an anti-gonococcal vaccine is essential to facilitate vaccine design, assessment and implementation. The modeling presented herein aims to fill these conceptual gaps, and inform future gonococcal vaccine development. Using an individual-based, epidemiological simulation model, gonococcal prevalence was simulated in a heterosexual population of 100,000 individuals after the introduction of vaccines with varied efficacy (10-100%) and duration of protection (2.5-20 years). Model simulations predict that gonococcal prevalence could be reduced by at least 90% after 20 years, if all 13-year-olds were given a non-waning vaccine with 50% efficacy, or a vaccine with 100% efficacy that wanes after 7.5 years. A 40% reduction in prevalence is achievable with a non-waning vaccine of only 20% efficacy. We conclude that a vaccine of moderate efficacy and duration could have a substantive impact on gonococcal prevalence, and disease sequelae, if coverage is high and protection lasts over the highest risk period (i.e., most sexual partner change) among young people.


Translating Research into Reality: Elimination of Lymphatic Filariasis from Haiti.
Research provides the essential foundation of disease elimination programs, including the global program to eliminate lymphatic filariasis (GPELF). The development and validation of new diagnostic tools and intervention strategies, critical steps in the evolution of GPELF, required a global effort. Lymphatic filariasis research in Haiti involved many partners and was directly linked to the development of the national elimination program and to the success achieved to date. Ongoing research efforts involving many partners will continue to be important in resolving the challenges faced by the program today in its final efforts to achieve elimination.


Scattering of a spherical wave by a small sphere: an elementary solution.
Wave scattering by objects that are small compared to the wavelength (Rayleigh scattering) is usually studied for plane incident waves. However, knowledge of the full Green's function of the problem becomes necessary when the separation of scatterers from either an interface or each other is comparable to the scatterers' dimensions. Here, an elementary analytic solution is derived for diffraction of a spherical sound wave by a small, soft sphere. The approximate solution is obtained from asymptotic expansions of an exact solution, holds everywhere outside the sphere, and reduces to classical results due to Kelvin and Rayleigh in appropriate special cases.


Re-reattachment of a fractured maxillary central incisor: a case study.
There has been a rise in incidence of dental trauma and crown fractures as reported in the literature. Children and teenagers are the most affected age groups, and the maxillary central incisors are the teeth most often affected. This article discusses reattachment techniques for the restoration of fractured teeth when the tooth fragment is recovered after a traumatic dental injury. This particular case study reports re-reattachment of a previously fractured and reattached tooth fragment.


Validation of the cognitive stimulation therapy (CST) program for people with dementia in Portugal.
Cognitive Stimulation Therapy (CST) is considered a gold-standard, evidence-based and cost-effective approach to improve cognitive function and quality of life of people with mild to moderate dementia. To validate CST for the Portuguese population and test its effectiveness. A single-blind, multi-center, randomized controlled trial recruited 112 older people with dementia. The primary outcome measure was cognition and secondary measures were quality of life, communication, autonomy, anxiety, depression, and global functioning. We also explored whether CST benefits people differently according to context, gender and level of cognitive reserve. Fifty-five people were randomized to the intervention and 57 to the control group. In the post-test, the intervention group significantly improved relative to controls in cognition (ADAS-Cog, p = 0.013), communication (HCS, p = 0.045), behaviour (CAPE-BRS, p = 0.017) and in global dementia rating (CDR, p = 0.008). Quality of life, depression and anxiety had no significant differences. The estimated number needed to treat was four for one to benefit a cognitive improvement (ADAS-Cog). Group CST is valid for the Portuguese population with benefits for people with mild to moderate dementia.


[Mechanism of high temperature promoting artemisinin biosynthesis in Artemisia annua].
Artemisia annua also known as Qinghao, is a kind of traditional Chinese medicine. Its active ingredient is artemisinin, a sesquiterpene lactone compound with a peroxy bridging group structure. A. annua is an effective antimalarial drug. Artemisinin, a secondary metabolite in A. annua, can be induced by many physical and chemical factors, such as salinity, moisture, light, and plant hormones. Temperature, as an important growth factor, also has a great influence on the synthesis of artemisinin. This article aims to study the effect of high temperature on inducing artemisinin biosynthesis in A. annua. The A. annua seedlings were placed at 25, 40 °C, and the samples were taken after 0, 3, 12 and 36 h. The content of artemisinin in each sample was determined by liquid chromatography-mass spectrometry. Total RNA was extracted from the samples, and then transcriptome sequencing and real-time fluorescence quantitative PCR were used to quantitatively analyze the expression of the key enzyme genes in artemisinin synthesis pathway and competition pathway. The results showed that artemisinin content was increased by 20%, 42% and 68% after 3, 12, 36 h of treatment at 40 °C. The expression levels of FDS, ALDH1, CYP71AV1 and ADS were up-regulated by 4.3, 3.3, 2.5, 1.9 times, and the expression levels of SQS and BPS were down-regulated by 37% and 90% respectively. In summary, high temperature can promote the biosynthesis of artemisinin by promoting the expression of synthetase genes in artemisinin synthesis pathway and inhibiting the expression of synthetase genes in artemisinin-competition pathway.


Gastrointestinal bleeding after percutaneous coronary intervention.
Percutaneous coronary intervention (PCI) is now performed in a wide range of patients with coronary artery disease. Complications of PCI include in-stent re-stenosis and in-stent thrombosis. According to the recent 2005 guidelines of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions, dual antiplatelet therapy with low-dose aspirin and thienopyridine derivatives such as ticlopidine and clopidogrel should be used in patients who have undergone PCI. A serious complication of dual antiplatelet therapy is bleeding, most of which arise from the gastrointestinal (GI) tract. In this article we review published studies about GI bleeding in patients who have undergone PCI. The prevalence of GI bleeding in patients who are administered dual antiplatelet therapy following PCI is approximately 2%, and GI bleeding after PCI is associated with increased morbidity, mortality, duration of hospitalization and cost. Advanced age, a history of peptic ulcer disease, co-administration of non-steroidal anti-inflammatory drugs, co-administration of anticoagulants, and physiological stress are considered to be the major risk factors for GI bleeding in patients undergoing antiplatelet therapy following PCI. Recent clinical and experimental studies indicate that administration of low-dose aspirin may also increase the risk of adverse events in the small intestine. Although some prophylactic strategies such as proton-pump inhibitor, H₂ receptor antagonist and eradication of Helicobacter pylori are proposed, there are few randomized controlled trials assessing the best strategy for the prevention of GI bleeding after PCI. Further extensive studies are required to ascertain the beneficial effect of prophylactic agents for dual antiplatelet therapy following PCI.


Collapsing health care in Serbia and Montenegro.
Serbia and Montenegro together form the Federal Republic of Yugoslavia. As well as the Serb majority this includes the mixed province of Vojvodina, the mainly Albanian population in Kosovo, and the large Muslim minority in Sandzak. Since the start of war in 1991 the attention and sympathies of the world have focused on Bosnia and Croatia. The United Nations imposed economic sanctions on the federal republic in 1992, although in theory medical supplies and aid are exempt. The economy has now collapsed under the triple burden of war, loss of trade between the republics, and UN sanctions. A major public health catastrophe is unfolding in the federal republic.


Post-myringotomy care: a prospective study.
Children with tympanostomy tubes have always been considered somewhat handicapped in regard to swimming and bathing. Their parents had to maintain constant surveillance to prevent then from getting water in their ears. A prospective study involving more than 1,000 children was conducted between June 1981 and August 1982 on two groups of randomly selected patients to determine the prevalence of suppurative otitis media and its relationship to bathing and swimming. One group had to follow strict rules to prevent water entering the ear (bathing caps, earplugs) whereas the other group was allowed to bathe and swim without any precaution upon the condition of using a polymyxin B/gramicidin ear drop combination at bedtime on the day they swam. The study shows no increase in prevalence of suppurative otitis media in the "open canal" group as compared to the "closed canal" group. Furthermore, the monthly distribution of infections shows a relatively evan distribution throughout the year. This study implies that swimming and bathing are safe for the vast majority of children with tympanostomy tubes and thus simplifies enormously the post-myringotomy care for the child, the parents, and the physician.


Fate of the mammalian cardiac neural crest.
A subpopulation of neural crest termed the cardiac neural crest is required in avian embryos to initiate reorganization of the outflow tract of the developing cardiovascular system. In mammalian embryos, it has not been previously experimentally possible to study the long-term fate of this population, although there is strong inference that a similar population exists and is perturbed in a number of genetic and teratogenic contexts. We have employed a two-component genetic system based on Cre/lox recombination to label indelibly the entire mouse neural crest population at the time of its formation, and to detect it at any time thereafter. Labeled cells are detected throughout gestation and in postnatal stages in major tissues that are known or predicted to be derived from neural crest. Labeling is highly specific and highly efficient. In the region of the heart, neural-crest-derived cells surround the pharyngeal arch arteries from the time of their formation and undergo an altered distribution coincident with the reorganization of these vessels. Labeled cells populate the aorticopulmonary septum and conotruncal cushions prior to and during overt septation of the outflow tract, and surround the thymus and thyroid as these organs form. Neural-crest-derived mesenchymal cells are abundantly distributed in midgestation (E9.5-12.5), and adult derivatives of the third, fourth and sixth pharyngeal arch arteries retain a substantial contribution of labeled cells. However, the population of neural-crest-derived cells that infiltrates the conotruncus and which surrounds the noncardiac pharyngeal organs is either overgrown or selectively eliminated as development proceeds, resulting for these tissues in a modest to marginal contribution in late fetal and postnatal life.


Spontaneously immortalised bovine mammary epithelial cells exhibit a distinct gene expression pattern from the breast cancer cells.
Spontaneous immortalisation of cultured mammary epithelial cells (MECs) is an extremely rare event, and the molecular mechanism behind spontaneous immortalisation of MECs is unclear. Here, we report the establishment of a spontaneously immortalised bovine mammary epithelial cell line (BME65Cs) and the changes in gene expression associated with BME65Cs cells. BME65Cs cells maintain the general characteristics of normal mammary epithelial cells in morphology, karyotype and immunohistochemistry, and are accompanied by the activation of endogenous bTERT (bovine Telomerase Reverse Transcriptase) and stabilisation of the telomere. Currently, BME65Cs cells have been passed for more than 220 generations, and these cells exhibit non-malignant transformation. The expression of multiple genes was investigated in BME65Cs cells, senescent BMECs (bovine MECs) cells, early passage BMECs cells and MCF-7 cells (a human breast cancer cell line). In comparison with early passage BMECs cells, the expression of senescence-relevant apoptosis-related gene were significantly changed in BME65Cs cells. P16INK4a was downregulated, p53 was low expressed and Bax/Bcl-2 ratio was reversed. Moreover, a slight upregulation of the oncogene c-Myc, along with an undetectable level of breast tumor-related gene Bag-1 and TRPS-1, was observed in BME65Cs cells while these genes are all highly expressed in MCF-7. In addition, DNMT1 is upregulated in BME65Cs. These results suggest that the inhibition of both senescence and mitochondrial apoptosis signalling pathways contribute to the immortality of BME65Cs cells. The expression of p53 and p16INK4a in BME65Cs was altered in the pattern of down-regulation but not "loss", suggesting that this spontaneous immortalization is possibly initiated by other mechanism rather than gene mutation of p53 or p16INK4a. Spontaneously immortalised BME65Cs cells maintain many characteristics of normal BMEC cells and exhibit non-malignant transformation. Although this cell line displays altered patterns of gene expression, it is clearly distinct from malignant breast cancer cell line. It showed that co-inhibition of cellular senescence and mitochondrial apoptosis pathways coordinates BME65Cs cells immortalisation. Additionally, mechanisms other than gene mutation are likely to be involved in regulation of cellular functions. This study provides an insight into the relationship between cell senescence and immortalisation. BME65Cs cells will be useful in future studies of cellular senescence and tumorigenesis.


An immunohistological study on the nephritis in chicks experimentally produced with avian nephritis virus.
One chick inoculated by a combined nasal and conjunctival sac route (in) and two chicks inoculated per os (io) died with visceral urate deposits at post inoculation days (dpi) 9 and 11. All infected chicks showed renal degeneration and inflammatory changes that originated from tubular cell necrosis. Avian nephritis virus (ANV) antigen was detected as cytoplasmic granules within the necrotic tubular epithelial cells. The serum uric acid was increased in in- and io-infected chicks 5 to 10 dpi and was coincident with the severity of the renal degeneration. Immunoglobulin (IgG and IgM)-containing cells were detected first in the renal lesion 5 and 7 dpi; they were coincident with the cell infiltration. IgG- and IgM-containing cells were demonstrated in the spleen 5 dpi and increased thereafter eight to 12 times more than those in non-infected control chicks. They were almost coincident with the detection of antibody against ANV. These findings suggested that ANV replication may stimulate the proliferative response of IgG- and IgM-containing cells in the spleen, and that the appearance of IgG- and IgM-containing cells in the kidney may also be closely associated with the clearance of ANV and regeneration of the renal lesion.


Quantitative assessment of left ventricular longitudinal function and myocardial deformation in Duchenne muscular dystrophy patients.
Duchenne muscular dystrophy (DMD) manifests in males mainly by skeletal muscle impairment, but also by cardiac dysfunction. The assessment of the early phases of cardiac involvement using echocardiography is often very difficult to perform in these patients. The aim of the study was to use cardiac magnetic resonance (CMR) strain analysis and mitral annular plane systolic excursion (MAPSE) in the detection of early left ventricular (LV) dysfunction in DMD patients. In total, 51 male DMD patients and 18 matched controls were examined by CMR. MAPSE measurement and functional analysis using feature tracking (FT) were performed. Three groups of patients were evaluated: A/ patients with LGE and LV EF < 50% (n = 8), B/ patients with LGE and LVEF ≥ 50% (n = 13), and C/ patients without LGE and LVEF ≥ 50% (n = 30). MAPSE and global LV strains of the 3 DMD groups were compared to controls (n = 18). Groups A and B had significantly reduced values of MAPSE, global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) in comparison to controls (p < 0.05). The values of MAPSE (11.6 ± 1.9 v 13.7 ± 2.7 mm) and GCS (- 26.2 ± 4.2 v - 30.0 ± 5.1%) were significantly reduced in group C compared to the controls (p < 0.05). DMD patients had decreased LV systolic function measured by MAPSE and global LV strain even in the case of normal LV EF and the absence of LGE. FT and MAPSE measurement provide sensitive assessment of early cardiac involvement in DMD patients.


Coordinate regulation of T cell activation by CD2 and CD28.
T cell activation requires co-engagement of the TCR with accessory and costimulatory molecules. However, the exact mechanism of costimulatory function is unknown. Mice lacking CD2 or CD28 show only mild deficits, demonstrating that neither protein is essential for T cell activation. In this paper we have generated mice lacking both CD2 and CD28. T cells from the double-deficient mice have a profound defect in activation by soluble anti-CD3 Ab and Ag, yet remain responsive to immobilized anti-CD3. This suggests that CD2 and CD28 may function together to facilitate interactions of the T cell and APC, allowing for efficient signal transduction through the TCR.


The study on SiO2 pattern fabrication using Ge1.5Sn0.5Sb2Te5 as resists.
Ge1.5Sn0.5Sb2Te5 (GSST) can be easily induced to phase transition from amorphous state to crystalline state by a laser direct writing (LDW) system. The results show that the crystalline phase of GSST is more durable against acid solution corrosion than the amorphous phase. So nano-scale patterns and structures can be formed on the GSST film resists using laser-induced phase change and wet etching. Moreover, reactive ion etching (RIE) technology was applied to transfer these patterns onto the SiO2 substrate. The result shows to the extent that GSST material has thermal resist characteristics with high resolution and well etching selectivity to SiO2 when etched in the CHF3, which is compatibility with the future nanofabricate processing.


Establishment of a CD4-positive plasmacytoma cell line (AMO1).
A human plasmacytoma cell line (AMO1) was established. The AMO1 cells had the light and electron microscopic characteristics typical of plasmacytoma cells and did not harbor Epstein-Barr virus. These cells expressed cytoplasmic immunoglobulin A kappa and the immunoglobulin heavy-chain gene (JH) and kappa light-chain gene (C kappa) were rearranged. Coexpression of a CD4 antigen and plasma cell antigens (CD38 and PCA-1) was an unusual and sustained feature. Neither the T-cell receptor beta nor the gamma chain gene displayed the rearranged form. Other lineage-specific surface antigens, namely T, B, monocytoid, and myeloid antigens, were all negative in AMO1. In accordance with the surface CD4 expression, polymerase chain reaction analysis indicated constitutive expression of CD4 mRNA, and the cytogenetic findings revealed that AMO1 cells had a derivative chromosome 12, which had a structural abnormality of the short arm carrying the CD4 gene locus. These findings provide strong evidence for the presence of CD4-positive malignant plasma cells and raise the possibility that the CD4 expression in the AMO1 cell line is closely associated with the derivative chromosome.


Antioxidative activity of microencapsulated gamma-oryzanol on high cholesterol-fed rats.
The effectiveness of microencapsulated gamma-oryzanol (M-gamma-OZ) was evaluated as an antioxidant in Sprague-Dawley rats. Lard containing 100 ppm of gamma-OZ (HCD III) or 100 ppm of M-gamma-OZ (HCD IV) was heated in an oven for 7 days, and the heat-treated lard as an ingredient in a high cholesterol diet (HCD) formulation was tested for analyzing in vivo cholesterol and lipid profiles. The HCDs containing fresh lard (HCD I) and heat-treated lard (HCD II) were fed to the rats for 4 weeks as control groups A and B, respectively, in this experiment. The liver thiobarbituric acid reactive substances values of group C (fed with HCD III) and group D (with HCD IV) were significantly lower (p < 0.05) than that of negative control, group B. One of the cholesterol oxidation products, 7-ketocholesterol, was not detected from group D, indicating that microencapsulation preserved antioxidative activity effectively. The levels of serum total cholesterol and lipoproteins, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein were also affected by heat-induced lipid oxidation.The M-gamma-OZ evidently decreased LDL-cholesterol content and increased HDL-cholesterol in blood samples of tested rats. These results suggested that the M-gamma-OZ was not only effective in inhibiting the hypercholesterolemia of serum and liver but also reduced the oxidation degree of lipids and cholesterol. Therefore, this microencapsulation can be a good potential technique to protect the antioxidant activity of gamma-OZ from heat-induced lipid oxidation.


Primary extramedullary plasmacytoma in cyclosporine-induced gingival overgrowth. A case report.
An unusual solitary extramedullary plasmacytoma developed in the gingiva of a 28 year-old male renal transplant patient with cyclosporine (CyA)-induced gingival overgrowth. On initial presentation, there was no suspicion of a tumor within the lesion. One year later, however, the lesion had increased progressively in size, and its surface was ulcerated. At this time, the lesion was excised by gingivectomy, and histopathological examination revealed plasmacytoma. CyA was discontinued and the patient has been closely observed for 4 years with no recurrence of the gingival lesion.


Cellular localization of type 1 plasminogen activator inhibitor messenger RNA and protein in murine renal tissue.
Type 1 plasminogen activator inhibitor (PAI-1) may be markedly increased in the plasma of patients with endotoxemia and/or renal disease. To investigate renal PAI-1 production during acute endotoxemia, a murine model system was used. Mice were injected with either saline alone or saline containing 50 micrograms endotoxin, and sacrificed 3 hours later and their tissues analyzed for PAI-1 messenger RNA (mRNA) and antigen. Northern blot analysis confirmed that the level of renal PAI-1 mRNA was greatly increased in the endotoxemic mice relative to the saline controls. In situ hybridization was then performed to determine the cellular localization of PAI-1 mRNA within the renal tissues. In the control kidneys, low levels of PAI-1 mRNA were detected in the renal papilla and in the muscular walls of renal arteries. However, in the endotoxemic mice, an intense hybridization signal for PAI-1 mRNA was observed in glomerular and peritubular cells. These cells also stained positively for von Willebrand factor antigen, an endothelial cell-specific marker. The PAI-1 mRNA hybridization signal could further be observed in peritubular endothelial cells in the medulla and in endothelial cells of veins and arteries throughout the kidney. Immunochemical analysis revealed that PAI-1 antigen co-localized to the cytoplasm of cells expressing PAI-1 mRNA. This study provides the first direct evidence that PAI-1 is induced in endothelial cells of the kidney during endotoxemia in vivo and suggests a role for PAI-1 in the pathogenesis of renal disease.


Toxicokinetics of topical sulfur mustard penetration, disposition, and vascular toxicity in isolated perfused porcine skin.
Sulfur mustard bis(2-chloroethyl) sulfide (HD) is a bifunctional alkylating agent that causes cutaneous vesication. The isolated perfused porcine skin flap is an in vitro model that has been used to study this toxic response. The purpose of this study was to formulate a toxicokinetic model of HD penetration and cutaneous disposition as an aid in correlating critical steps in the pathogenesis of vesication to HD concentrations in different regions of skin. [14C]HD was dosed topically in ethanol at 10.0 mg/ml in a 7.5-cm2 dosing site and venous efflux samples were collected over 2, 4, or 8 hr. At the termination of the experiment, stratum corneum tape strips, core biopsies for serial sections, and the entire skin flap were collected for radioassay. Peak 14C-radiolabel flux occurred within 5 to 60 min in all skin flaps, much earlier than signs of HD-induced toxicity. A toxicokinetic model was used to quantitate the time profile of HD disposition in different skin compartments. Estimates of vascular and extracellular volume changes due to topical HD toxicity were estimated using radiolabeled albumin and inulin infusions. A second toxicokinetic model, with a time-variant distribution rate, was used to simulate volume changes. In order to accurately predict HD disposition, it was necessary to add another compartment as a reservoir for slowly released metabolites of HD. This model provides a quantitative profile of the time course of HD (or metabolites) disposition within skin which would aid in the interpretation of mechanistic studies of vesication as well as in designing interventive antivesicant drug strategies.


Ultrasonographic evaluation of common duct diameter in pre and post cholecystectomy patients.
Thirty four patients with gall bladder disease and normal common duct were investigated prospectively by ultrasonography just before cholecystectomy and at periodic intervals of 1 months, 2 months, 3 months and once in 4-6 months after cholecystectomy. The pre and post cholecystectomy common duct diameters were measured at each visit and compared with each other to determine the statistical significance. No significant change (p > 0.05) occurred in common duct diameter following cholecystectomy.


[4 + 2] Benzannulation of 3-Alkenylpyrroles/Thiophenes with Propargylic Alcohols: Access to Substituted Indoles, Benzothiophenes, and Aza[5]helicenes.
An efficient and practical one-pot [4 + 2] benzannulation method to produce highly substituted indoles and 1-benzothiophenes via sequential acid-catalyzed propargylation/base-mediated cycloisomerization reactions has been developed. This method allows access to differently substituted (mainly on phenyl ring) indoles and 1-benzothiophenes from the reaction of 3-alkenylpyrroles/-thiophenes as C4 synthons with 1-aryl/1-heteroaryl propargylic alcohols as C2 synthons. Interestingly, dialkynyl substrates can undergo tandem benzannulations to give substituted aza[5]helicenes in 82-83% yield.


Transanal total mesorectal excision for rectal cancer: it's come a long way and here to stay.
Transanal total mesorectal excision (TaTME) was introduced as a novel technique to deal with rectal cancers. Its transanal approach offered the shortest distance to approach a challenging location, allowing an excellent visualization of the distal resection margin. Since its introduction in 2010, a significant amount of research has been put in to measure its development. In this review, we look at its ancestry, the genesis for its introduction and continued evolution as well as some of the important outcomes in its journey thus far. The importance of a structured and proctored learning journey is also stressed to enable the safe application and development of this technique. Beyond this, the TaTME movement has progressed relentlessly and its utility has been expanded to the management of benign conditions such as inflammatory bowel disease, Hartman reversals, and anastomotic strictures. We believe that the continued development and adoption of TaTME worldwide is here to stay.


Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model.
Inhalation of N-chlorotaurine (NCT), an endogenous new broad spectrum non-antibiotic anti-infective, has been shown to be very well tolerated in the pig model recently. In the present study, inhaled NCT was tested for tolerability and efficacy in the infected bronchopulmonary system using the same model. Anesthetized pigs were inoculated with 20 ml of a solution containing approximately 108 CFU/ml Streptococcus pyogenes strain d68 via a duodenal tube placed through the tracheal tube down to the carina. Two hours later, 5 ml of 1% NCT aqueous solution (test group, n = 15) or 5 ml of 0.9% NaCl (control group, n = 16) was inhaled via the tracheal tube connected to a nebulizer. Inhalation was repeated every hour, four times in total. Lung function and haemodynamics were monitored. Bronchoalveolar lavage samples were removed for determination of colony forming units (CFU), and lung samples for histology. Arterial pressure of oxygen (PaO2) decreased rapidly after instillation of the bacteria in all animals and showed only a slight further decrease at the end of the experiment without a difference between both groups. Pulmonary artery pressure increased to a peak 1-1.5 h after application of the bacteria, decreased in the following hour and remained constant during treatment, again similarly in both groups. Histology demonstrated granulocytic infiltration in the central parts of the lung, while this was absent in the periphery. Expression of TNF-alpha, IL-8, and haemoxygenase-1 in lung biopsies was similar in both groups. CFU counts in bronchoalveolar lavage came to 170 (10; 1388) CFU/ml (median and 25 and 75 percentiles) for the NCT treated pigs, and to 250 (10; 5.5 × 105) CFU/ml for NaCl treated pigs (p = 0.4159). Inhaled NCT at a concentration of 1% proved to be very well tolerated also in the infected bronchopulmonary system. This study confirms the tolerability in this delicate body region, which has been proven in healthy pigs previously. Regarding efficacy, no conclusions can be drawn, mainly because of the limited test period of the model.


What is known about pediatric antiphospholipid syndrome?
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by vascular thrombosis and/or pregnancy morbidity associated with the persistent presence of antiphospholipid antibodies (aPL) including lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and anti-β2 glycoprotein I antibodies (aβ2GPI). APS is considered as the most common acquired hypercoagulation state of autoimmune origin in children. Unfortunately, data about incidence, prevalence, thrombosis risk and effective treatment in paediatric APS are limited and unmethodical. Expert commentary: This review summarizes recent clinical, laboratory and therapy characterization of paediatric APS and emphasizes the differences between paediatric and adult populations.


[Relationship of coronary artery calcification identified by electron beam tomography with age and gender].
To investigate the relationship of coronary artery calcification identified by electron beam tomography with age and gender. Electron beam tomography was performed in 654 patients to detect coronary artery calcification. Examinations were done with electron beam tomography (Imatron C-150 XP), using prospective electrocardiography triggering to prevent cardiac motion artifacts. Total calcification scores were calculated based on the number, area and computed tomographic number of the calcifications. The influence of age and gender on the presence and amount of coronary artery calcification were evaluated. There were significant differences (p < 0.001) in mean total calcification scores between men and women. Men always had more coronary artery calcification than women at all age groups. The youngest patient with coronary artery calcification was below 40 years of age in men and above 40 years of age in women. The difference in the prevalence of coronary artery calcification between men and women was great at younger ages, and decreased after age 60. The difference in prevalence of coronary artery calcification for men and women was starting to be decreased after age 60. We observed that coronary artery calcification, a marker of arteriosclerosis, is strongly associated with age and gender.


[Hydration status and health].
Water is an important component of human body and plays a variety of important physiological roles. The intake and discharge of human water is in a dynamic equilibrium. Insufficient water intake will affect the hydration status of human body, which in turn affects cognition and health. Therefore, maintaining proper hydration status is of great importance for maintaining and promoting the health of the body. There were many indicators to evaluate the hydration status of body, including urine and blood plasma biomarkers. It is of great significance to evaluate the hydration status of body, keep the body in a suitable hydration status by replenishing water in time. The lack of drinking water in different populations in China is common, but it has not yet received enough attention and needs to carry out corresponding health education.


GDNF-RET signaling in ER-positive breast cancers is a key determinant of response and resistance to aromatase inhibitors.
Most breast cancers at diagnosis are estrogen receptor-positive (ER(+)) and depend on estrogen for growth and survival. Blocking estrogen biosynthesis by aromatase inhibitors has therefore become a first-line endocrine therapy for postmenopausal women with ER(+) breast cancers. Despite providing substantial improvements in patient outcome, aromatase inhibitor resistance remains a major clinical challenge. The receptor tyrosine kinase, RET, and its coreceptor, GFRα1, are upregulated in a subset of ER(+) breast cancers, and the RET ligand, glial-derived neurotrophic factor (GDNF) is upregulated by inflammatory cytokines. Here, we report the findings of a multidisciplinary strategy to address the impact of GDNF-RET signaling in the response to aromatase inhibitor treatment. In breast cancer cells in two-dimensional and three-dimensional culture, GDNF-mediated RET signaling is enhanced in a model of aromatase inhibitor resistance. Furthermore, GDNF-RET signaling promoted the survival of aromatase inhibitor-resistant cells and elicited resistance in aromatase inhibitor-sensitive cells. Both these effects were selectively reverted by the RET kinase inhibitor, NVP-BBT594. Gene expression profiling in ER(+) cancers defined a proliferation-independent GDNF response signature that prognosed poor patient outcome and, more importantly, predicted poor response to aromatase inhibitor treatment with the development of resistance. We validated these findings by showing increased RET protein expression levels in an independent cohort of aromatase inhibitor-resistant patient specimens. Together, our results establish GDNF-RET signaling as a rational therapeutic target to combat or delay the onset of aromatase inhibitor resistance in breast cancer.


Cambarus (Jugicambarus) adustus, a new species of crayfish from northeastern Kentucky delimited from the Cambarus (J.) aff. dubius species complex.
A new species of burrowing crayfish, Cambarus (Jugicambarus) adustus, is described from Lewis County in northeastern Kentucky, USA. The new species is most similar morphologically to C. dubius. Cambarus adustus coloration differs from C. dubius by lacking red, orange and blue hues, and instead is brown over the entire body surface. Morphological differences between C. dubius and C. adustus exist in the form I male gonopod, with C. adustus possessing a caudal knob, while C. dubius does not. In addition, the lateral carapace of C. adustus is distinctly tuberculate, whereas in C. dubius the carapace lacks extensive tuberculation. Cambarus (J.) adustus appears to have an extremely small geographic range (~19.5 km2), and as such we suggest its consideration for both state and federal levels of protection.


Adolescents' Views Regarding Uses of Social Networking Websites and Text Messaging for Adolescent Sexual Health Education.
BACKGROUND: Adolescents frequently report barriers to obtaining sexual health education. PURPOSE: The purpose of this study was to determine adolescents' views regarding how new technologies could be used for sexual health education. METHODS: Focus groups were conducted with a purposeful sample of adolescents between 14 and 19 years old. Facilitators asked participants for their views regarding use of social networking web sites (SNSs) and text messaging for sexual health education. Tape-recorded data was transcribed; transcripts were manually evaluated then discussed to determine thematic consensus. RESULTS: A total of 29 adolescents participated in 5 focus groups. Participants were 65.5% female. Three themes emerged from our data. First, adolescents preferred sexual health education resources that are accessible. Second, adolescents preferred online resources that are trustworthy. Third, adolescents discussed preference for "safe" resources. DISCUSSION: Adolescents were enthusiastic and insightful regarding technology for enhancing sexual health education. The themes that influence adolescents' preferences in sexual health education using technology are similar to barriers that exist in other aspects of adolescent health communication. TRANSLATION TO HEALTH EDUCATION PRACTICE: Findings suggest ways in which health organizations can understand adolescents' views and concerns about how their interactions with professionals take place regarding sexual health.


Neoadjuvant chemotherapy followed by surgery in cervical cancer: past, present and future.
Cisplatin-based concurrent chemoradiation is the standard treatment for locally advanced cervical cancer. In view of the difficulties associated with implementation of standard radiation protocols in low- and middle-income countries and the associated toxicities of chemoradiation, neoadjuvant chemotherapy followed by surgery has been tried as an alternative treatment for locally advanced cervical cancer. A comprehensive review was undertaken of the existing literature, caveats and potential avenues of neoadjuvant chemotherapy followed by surgery compared with chemoradiation in locally advanced cervical cancer. Randomized studies conducted in the pre-chemoradiation era comparing neoadjuvant chemotherapy followed by surgery with definitive radiotherapy alone showed favorable outcomes with the chemo-surgical approach. However, contemporary studies evaluating the role of neoadjuvant chemotherapy followed by surgery have failed to establish this approach as the standard. About 25-30% of patients who undergo neoadjuvant chemotherapy remain inoperable and require definitive chemoradiation. A similar proportion of patients would require adjuvant (chemo)radiation after neoadjuvant chemotherapy followed by surgery, resulting in excessive morbidity. Evaluation of time trends across the past few decades reveals that the advancements in delivery of radiation (external beam and brachytherapy) have translated into improvement in outcomes for locally advanced cervical cancer, while a similar trend was not observed for surgery or chemotherapy. Neoadjuvant chemotherapy followed by surgery cannot be considered a standard of care in patients with locally advanced cervical cancer. This approach needs further clinical research to generate robust high-quality evidence especially for the sub-sets that might potentially benefit in terms of survival, toxicity and quality of life, against the gold standard treatment of concomitant chemoradiation.


The evolution of worker caste diversity in social insects.
Morphological diversification of workers is predicted to improve the division of labor within social insect colonies, yet many species have monomorphic workers. Individual-level selection on the reproductive capacities of workers may counter colony-level selection for diversification, and life-history differences between species (timing of caste determination, colony size, genetic variation available) may mediate the strength of this selection. We tested this through phylogenetically independent contrast analyses on a new data set for 35 ant species. Evidence was found that early divergence of queen-worker developmental pathways may facilitate the evolution of worker diversity because queen-worker dimorphism was strongly positively associated with diversity. By contrast, risks for colonies that invest in specialized workers and colony size effects on costs of worker reproduction seem unlikely to strongly affect the evolution of worker diversity because there was no significant association between colony size and diversity when controlling statistically for queen-worker dimorphism. Finally, worker diversity was greater in species with multiple lineages per colony, and it was negatively associated with relatedness in monogynous species. This could be due to high intracolonial genetic variance favoring the expression and evolution of great worker diversity or to diversity evolving more easily when there is selection for repression of worker reproduction (worker policing).


Cleanup protocol for 226Ra-contaminated cobbly soil at UMTRA Project sites.
The nonuniform distribution of 226Ra and other radiological contamination of cobbly soil encountered on several Uranium Mill Tailings Remedial Action Project sites is presented and discussed, and the concomitant challenges to the intent and implementation of the U.S. Environmental Protection Agency's soil cleanup standards are noted. In response to technical assessments and information presented to the U.S. Nuclear Regulatory Commission by the U.S. Department of Energy, the Nuclear Regulatory Commission has recently resolved the dilemma by concluding that compliance with Environmental Protection Agency soil cleanup standards for cobby soil at Uranium Mill Tailings Remedial Action Project sites would be adequately attained using bulk radionuclide concentrations, instead of requiring that the radionuclide concentration of the finer soil fraction passing a #4 mesh sieve met the standards. A Nuclear Regulatory Commission-approved procedure developed for cobbly soil remediation is outlined and discussed. The site-specific implementation of this procedure at Uranium Mill Tailings Remedial Action Project sites containing cobbly soil is estimated to save millions of dollars.


Diffuse alveolar hemorrhage in systemic lupus erythematosus: a single center retrospective study in Taiwan.
This study is to describe our clinical experience of diffuse alveolar hemorrhage (DAH) in patients with systemic lupus erythematosus (SLE) in Taiwan. From July 1994 to June 2001, eight patients of DAH among 1541 different SLE patients (0.52%) admitted to the Chang Gung Memorial Hospital were included for chart review. Dyspnea (100%) and fever (87.5%) were the most common symptoms instead of hemoptysis (62.5%). The most common extrapulmonary presentation was renal involvement (100%), which included clinical nephritis, nephrotic syndrome or acute renal failure. The overall mortality rate was 50%. Two pregnant patients were successfully treated with combined plasmapheresis and continuous venovenous hemofiltration in addition to high dose corticosteroid. Analysis of the prognostic factors showed that the higher APACHE II (Acute physiology, Age and Chronic Health Evaluation) and organ system failure (OSF) scores, but not the SLE activity index (SLEDAI), were associated with the greater mortality. The higher serum creatinine level or the need of hemodialysis did not adversely affect the survival. In conclusion, DAH in SLE patients are often accompanied with multiple organ failure, aggressive immunosuppressive therapy and multiple modalities of extracorporeal organ support should be started early for a favorable outcome.


Epigenetic control of centromere: what can we learn from neocentromere?
The centromere is the special region on a chromosome, which serves as the site for assembly of kinetochore complex and is essential for maintaining genomic integrity. Neocentromeres are new centromeres that form on the non-centromeric regions of the chromosome when the natural centromere is disrupted or inactivated. Although neocentromeres lack the typical features found in centromeres, cells with neocentromeres divide normally during mitosis and meiosis. Neocentromeres not only arise naturally but their formation can also be induced experimentally. Therefore, neocentromeres are a great tool for studying functions and formation of centromeres. To study neocentromeres and use that knowledge to gain insights into the epigenetic regulation of canonical centromeres. Here, we review the characteristics of naturally occurring centromeres and neocentromeres and those of experimentally induced neocentromeres. We also discuss the mechanism of centromere formation and epigenetic regulation of centromere function, which we learned from studying the neocentromeres. Although neocentromeres lack main features of centromeres, such as presence of repetitive ⍺-satellite DNA and pericentric heterochromatin, they behave quite similar to the canonical centromere, indicating the epigenetic nature of the centromere. Still, further investigation will help to understand the formation and maintenance of the centromere, and the correlation to human diseases. Neocentromeres helped us to understand the formation of canonical centromeres. Also, since neocentromeres are associated with certain cancer types, knowledge about them could be helpful to treat cancer.


Is high level of disability an indication for spinal fusion? Analysis of long-term outcome after posterior lumbar interbody fusion using carbon fiber cages.
Posterior lumbar interbody fusion is a recognized procedure for the treatment of back pain associated with degenerative disc disease and segmental instability. It allows decompression of the spinal canal and circumferential fusion through a single posterior incision. Sixty-five consecutive patients who underwent posterior lumbar interbody fusion using carbon cages and pedicle fixation between 1993 and 2000 were recruited and contacted with a postal survey. Clinical outcome was assessed by the postoperative clinical findings and complications and the fusion rate, which was assessed using the scoring system described by Brantigan and Steffee. Functional outcome was measured by using improvement in the Oswestry Disability Index, return to work, and satisfaction with the surgical outcome. The determinants of functional relief were analyzed against the improvement in disability using multiple regression analysis. The mean postoperative duration at the time of the study was 4.4 years. Overall radiologic fusion rate was 98%. There was a significant improvement in Oswestry Disability Index (P < 0.01). There was 84% satisfaction with the surgical procedure and 61% return to predisease activity level and full employment. We found preoperative level of disability to be the best determinant of functional recovery irrespective of age or the degree of psychological morbidity and litigation (P < 0.01). The combination of posterior lumbar interbody fusion and posterior instrumented fusion is a safe and effective method of achieving circumferential segmental fusion. A direct relationship between preoperative level of disability and functional recovery suggests that disability should be measured preoperatively and spinal fusion should be performed to alleviate disability caused by degenerative spine.