Is puberty getting earlier? The views of doctors and teachers.
To determine the views of teachers, general practitioners (GPs) and paediatricians about whether there has been a recent change in the timing of the onset of puberty in children in the UK and in the timing of menarche in girls. Questionnaires were sent to a stratified random sample of each professional group. In relation to girls, almost 80% of teachers believe that the onset of puberty is occurring earlier and 73% feel that the menarche is occurring earlier. Those who had been working for longer than 10 years were more likely to say that the age of onset of puberty had decreased. GPs feel that both puberty and menarche are starting earlier, whereas paediatricians were evenly divided between those who thought puberty was starting earlier and those who thought that the timing had not changed. In boys, professionals generally believe that the timing of the onset of puberty has not altered significantly. Further study is required to determine whether puberty is really occurring earlier in girls.


Recombinant follicle stimulating hormone is effective in poor responders to highly purified follicle stimulating hormone.
Ovarian stimulation in cases of poor ovarian responsiveness is an important challenge in in-vitro fertilization (IVF) programmes. Despite improvements in oocyte number and quality, an ideal ovarian stimulation strategy has yet to be defined. Here, the results of ovarian stimulation with recombinant follicle stimulating hormone (rFSH) in 28 poor responders to highly purified FSH (FSH-HP) with high basal concentrations of FSH are reported. The protocols used on the FSH-HP and rFSH cycles were identical with the sole exception of the FSH preparation: triptorelin 0.1 mg/day (gonadotrophin-releasing hormone, GnRH-agonist short protocol) and the starting FSH dose of 300 IU/day were administered from day 2 of the menstrual cycle. Ovarian outcome was classified as 'normal', 'intermediate' and 'poor', depending on the number of mature oocytes retrieved and the peak serum oestradiol concentration. Nine of the 28 subjects had an intermediate ovarian response to re-stimulation with rFSH. In the 26 patients who received human chorionic gonadotrophin on both cycles, re-stimulation resulted in a significant increase (P < 0.05) in the mean number of mature oocytes (2.4 +/- 1.4 versus 1.7 +/- 0.8), mean peak oestradiol concentration (606 +/- 252 versus 443 +/- 32 pg/ml) and fertilization rate (73.0 versus 53.3%). Four pregnancies were achieved. It is concluded that rFSH in a GnRH-agonist short protocol improves the ovarian outcome in poor responders to FSH-HP with high basal concentrations of FSH.


Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT.
Ceramide is synthesized at the endoplasmic reticulum (ER) and transported to the Golgi apparatus by CERT for its conversion to sphingomyelin in mammalian cells. CERT has a pleck-strin homology (PH) domain for Golgi targeting and a START domain catalyzing the intermembrane transfer of ceramide. The region between the two domains contains a short peptide motif designated FFAT, which is supposed to interact with the ER-resident proteins VAP-A and VAP-B. Both VAPs were actually co-immunoprecipitated with CERT, and the CERT/VAP interaction was abolished by mutations in the FFAT motif. These mutations did not affect the Golgi targeting activity of CERT. Whereas mutations of neither the FFAT motif nor the PH domain inhibited the ceramide transfer activity of CERT in a cell-free system, they impaired the ER-to-Golgi transport of ceramide in intact and in semi-intact cells at near endogenous expression levels. By contrast, when overexpressed, both the FFAT motif and the PH domain mutants of CERT substantially supported the transport of ceramide from the ER to the site where sphingomyelin is produced. These results suggest that the Golgi-targeting PH domain and ER-interacting FFAT motif of CERT spatially restrict the random ceramide transfer activity of the START domain in cells.


From soft to hard rod behavior in liquid crystalline suspensions of sterically stabilized colloidal filamentous particles.
The liquid crystalline phase behavior of a colloidal system of sterically stabilized rods is reported. Our colloidal suspensions consist of highly monodisperse, semi-flexible filamentous viruses which have been coated with neutral hydrophilic polymers by irreversibly binding poly(ethylene glycol) (PEG) to the surface of the virus particles. Depending on the size of the grafted polymer, up to three different phase transitions are observed (isotropic-to-chiral nematic, chiral nematic-to-smectic, and smectic-to-columnar). Each phase transition is shown to be independent of ionic strength, confirming the steric stabilization of the viral colloids. A direct, i.e. without any free parameters, comparison with theory and computer simulations of the volume fraction associated with the phase transition can be performed, showing a quantitative agreement with hard rod behavior at a low polymer chain size, and some deviation stemming from soft repulsion by increasing the polymer thickness coating of the rod. Specifically, we demonstrate that the columnar mesophase is not stabilized by electrostatic repulsion, and we discuss the conditions of its existence.


Gender differences in ondansetron pharmacokinetics in rats.
It has been reported that ondansetron is primarily metabolized via hepatic CYP2D and 3A1/2 in male Sprague-Dawley rats, and CYP2D1 and 3A2 are male dominant and male specific isozymes, respectively, in rats. Thus, it could be expected that the pharmacokinetics of ondansetron would be changed in male rats compared with those in female rats. Thus, gender-different ondansetron pharmacokinetics were evaluated after its intravenous or oral administration at a dose of 8 mg/kg to male and female Sprague-Dawley rats. After intravenous administration of ondansetron to male rats, the AUC and time-averaged non-renal clearance (Clnr) of the drug were significantly smaller (22.6% decrease) and faster (27.3% increase), respectively, than those in female rats. This probably could be due to faster hepatic blood flow rate in male rats. After oral administration of ondansetron to male rats, the AUC of the drug was also significantly smaller (58.8% decrease) than that in female rats, and this could have been due mainly to increased intestinal metabolism of ondansetron in addition to increased hepatic metabolism of the drug in male rats.


[Laparoscopic cholecystectomy during pregnancy].
The decision whether to perform cholecystectomy during pregnancy, and in what manner, is complex. A 26-year-old pregnant woman was admitted because of persistent biliary colic, which did not respond to conservative treatment. Laparoscopic cholecystectomy was done, with a normal course and without negative effects on the pregnancy. Contraindications to laparoscopic cholecystectomy are becoming fewer as technique improves and experience accumulates. This case report is added to the other few reported, which reinforce the view that pregnancy should no longer be considered a contraindication to laparoscopic cholecystectomy.


A new species of Echinostoma (Trematoda: Echinostomatidae) from the 'revolutum' group found in Brazil: refuting the occurrence of Echinostoma miyagawai (=E. robustum) in the Americas.
Although Echinostoma robustum (currently a synonym of E. miyagawai) was reported in the Americas based on molecular data, morphological support on adult parasites is still required. Herein, a new species of Echinostoma is described based on worms found in a chicken from Brazil. Molecular phylogenetic analyses based on 28S (1063 bp), ITS (947 bp) and Nad-1 (442 bp) datasets reveal the inclusion of the new species within Echinostoma 'revolutum' species complex. Moreover, it was verified the conspecificity between cercariae previously identified as E. robustum in Brazil [identical ITS and only 0.3% of divergence (1 nucleotide) in Nad-1]. Species discovery analyses show that these two isolates form an independent lineage (species) among Echinostoma spp. Compared to E. miyagawai, the new species presents relatively high divergence in Nad-1 (7.88–9.09%). Morphologically, the specimens are distinguished from all nominal species from the 'revolutum' species complex by the more posterior position of the testes (length of post-testicular field as a proportion of body length about 20%). They further differ from E. miyagawai and South American Echinostoma spp. by the higher proportion of forebody to the body length. Therefore, combined molecular and morphological evidence supports the proposal of the species named here as Echinostoma pseudorobustum sp. nov.


Synthesis of substituted nitroolefins: a copper catalyzed nitrodecarboxylation of unsaturated carboxylic acids.
A novel, mild and convenient method for the nitrodecarboxylation of substituted cinnamic acid derivatives to their nitroolefins is achieved using a catalytic amount of CuCl (10 mol%) and tertbutyl nitrite (2 equiv.) as a nitrating agent in the presence of air. This reaction provides a useful method for the synthesis of β,β-disubstituted nitroolefin derivatives, which are generally difficult to access from other conventional methods. Additionally, this reaction is selective as the E-isomer of the acid derivatives furnishes the corresponding E-nitroolefins. One more salient feature of the method is, unlike other methods, no metal nitrates or HNO3 are employed for the transformation.


Assay and Characteristics of Circadian Rhythmicity in Liquid Cultures of Neurospora crassa.
Previous work on circadian rhythms of Neurospora crassa has been done almost exclusively with cultures expressing rhythmic conidiation and growing on solid agar medium. Such conditions severely restrict the kinds of biochemical experiments that can be carried out. We have now developed systems which allow indirect assay of circadian rhythmicity in liquid culture. Neurospora was grown in glucose and acetate liquid media under conditions which result in a range of growth rates and morphologies. Liquid media were inoculated with conidia and the cultures were grown in constant light for 33 or 48 hours, by which time floating mycelial pads had formed. Experimental pieces of mycelium then were cut and placed in fresh new liquid medium. As controls, other pieces of mycelium were cut and put directly on solid agar medium in race tubes. All cultures were transferred to constant darkness at this time. This light-to-dark transition set the phase of the circadian clock of both the liquid and solid cultures. At various times after the light-to-dark transition, the mycelial pieces in the liquid were transferred in the dark to solid medium in race tubes, where they grew normally and conidiated rhythmically. Comparison of the phase of the rhythm in these race tubes to the controls demonstrated that, under appropriate conditions, the circadian clock of the liquid cultures functions normally for at least two cycles in constant conditions. Using these culture systems, a significantly greater variety of biochemical studies of circadian rhythmicity in Neurospora is now possible.


Essential oils from stem and leaves of Angelica urumiensis (Mozaffarian) from Iran.
The composition of essential oils of the leaves and stem of Angelica urumiensis were analysed by chromatography-mass spectrometry. Overall, 58 volatile components were identified on the basis of their mass spectra characteristics and retention indices. Twenty-seven compounds were identified in the oil of the leaves, comprising 94.69% of the total oil, in which alpha-cadinol (20.2%), palmitic acid (14.14%), hexahydrofarnesyl acetone (10.03%), 1-dodecanol (7.55%), linoleic acid (6.37%) and oleic acid (5.34%) were the major constituents. Oxygenated sesquiterpenes and fatty acids were the main groups of compounds with 30.7% and 25.85%, respectively. Fifty compounds, representing 96.35% of the total oil, were identified in the stem oil. Palmitic acid (13.37), alpha-cadinol (9.24%), (epi)-alpha-cadinol (5.76%) and delta-cadenine (6.11%) were the major compounds. Sesquiterpenes and oxygenated sesquiterpenes dominated in the oil, comprising 28.03% and 20.9%, respectively. The chemical compounds of the essential oils showed that there are only 22 common compounds between two parts.


Premature atherosclerosis is associated with hypovitaminosis D and angiotensin-converting enzyme inhibitor non-use in lupus patients.
The ultimate goal is to identify and target modifiable risk factors that will reduce major cardiovascular events in African American lupus patients. As a first step toward achieving this goal, this study was designed to explore risk factor models of preclinical atherosclerosis in a predominantly African American group of patients with systemic lupus erythematosus (SLE) using variables historically associated with endothelial function in nonlupus populations. Fifty-one subjects with SLE but without a history of clinical cardiovascular events were enrolled. At entry, a Framingham risk factor history and medication list were recorded. Sera and plasma samples were analyzed for lipids, lupus activity markers and total 25-hydroxyvitamin D (25 OH)D) levels. Carotid ultrasound measurements were performed to determine total plaque area (TPA) in both carotids. Cases had TPA values above age-matched controls from a vascular prevention clinic population. Logistic regression and machine learning analyses were performed to create predictive models. 25(OH)D levels were significantly lower, and SLE disease duration was significantly higher in cases. 25(OH)D levels inversely correlated with age-adjusted TPA. Angiotensin-converting enzyme (ACE) inhibitor nonuse associated with case status. Logistic regression models containing ACE inhibitor use, 25(OH)D levels and low-density lipoprotein levels had a diagnostic accuracy of 84% for predicting accelerated atherosclerosis. Similar results were obtained with machine learning models, but hydroxychlo-roquine use associated with controls in these models. This is the first study to demonstrate an association between atherosclerotic burden and 25(OH)D insufficiency or ACE inhibitor nonuse in lupus patients. These findings provide strong rationale for the study of ACE inhibitors and vitamin D replenishment as preventive therapies in this high-risk population.


Rilpivirine attenuates liver fibrosis through selective STAT1-mediated apoptosis in hepatic stellate cells.
Liver fibrosis constitutes a major health problem worldwide due to its rapidly increasing prevalence and the lack of specific and effective treatments. Growing evidence suggests that signalling through cytokine-activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways regulates liver fibrosis and regeneration. Rilpivirine (RPV) is a widely used anti-HIV drug not reported to produce hepatotoxicity. We aimed to describe the potential hepatoprotective effects of RPV in different models of chronic liver injury, focusing on JAK-STAT signalling regulation. The effects of RPV on hepatic steatosis, inflammation and fibrogenesis were studied in a nutritional mouse model of non-alcoholic fatty liver disease, carbon tetrachloride-induced fibrosis and bile duct ligation-induced fibrosis. Primary human hepatic stellate cells (hHSC) and human cell lines LX-2 and Hep3B were used to investigate the underlying molecular mechanisms. RPV exerted a clear anti-inflammatory and antifibrotic effect in all the in vivo models of liver injury employed, and enhanced STAT3-dependent proliferation in hepatocytes and apoptosis in HSC through selective STAT1 activation. These results were reproduced in vitro; RPV undermined STAT3 activation and triggered STAT1-mediated pathways and apoptosis in HSC. Interestingly, this selective pro-apoptotic effect completely disappeared when STAT1 was silenced. Conditioned medium experiments showed that HSC apoptosis activated STAT3 in hepatocytes in an interleukin-6-dependent mechanism. RPV ameliorates liver fibrosis through selective STAT1-dependent induction of apoptosis in HSC, which exert paracrinal effects in hepatocytes, thus promoting liver regeneration. RPV's actions may represent an effective strategy to treat chronic liver diseases of different aetiologies and help identify novel therapeutic targets.


[Farmland ecosystem service and its formation mechanism].
Farmland ecosystem service has a real and far-reaching effect on the sustainable development of human society, and its study is one of the hotspots in ecology. This paper introduced the connotations of farmland ecosystem service and its valuation methodology, and summarized the present status in researching the formation mechanism of farmland ecosystem service from the aspects of the characteristics of abiotic environment, biota, ecosystem process, and human activity. It's considered that besides its importance in supplying human society a great number of products, farmland ecosystem is of significance in providing environmental service and maintaining regional ecological safety. Abiotic environment, biota, ecosystem process, and their interactions are the bases of the formation of farmland ecosystem service, and human activity is the primary driving force. It's imperative to build up an indices system to valuate farmland ecosystem service, and to strengthen the research of the effects of human activity on the farmland ecosystem service formation.


Regression of oral leukoplakia with alpha-tocopherol: a community clinical oncology program chemoprevention study.
Oral leukoplakia is an important model for developing chemoprevention approaches for lesions in the upper aerodigestive tract. These lesions most often result from exposure to carcinogens such as tobacco and alcohol and may precede development of invasive cancer. The potent antioxidant alpha-tocopherol (vitamin E) has prevented the development of cancers of the oral cavities in animal models. The objectives of this study were to evaluate the toxicity and efficacy of alpha-tocopherol in patients with oral leukoplakia and to assess the feasibility of performing chemoprevention trials through the network of the Community Clinical Oncology Program (CCOP). A single-arm phase II study using the nontoxic agent alpha-tocopherol to treat oral premalignant leukoplakia was performed at seven institutions affiliated with the CCOP through The University of Texas M. D. Anderson Cancer Center. Patients with symptomatic leukoplakia or dysplasia were treated orally with alpha-tocopherol (400 IU) twice daily for 24 weeks. Follow-up was performed at 6, 12, and 24 weeks after the start of treatment to assess toxicity and response, and serum alpha-tocopherol levels were determined at baseline and at 6 and 24 weeks. Of the 43 patients who have completed 24 weeks of treatment, 20 (46%) had clinical responses and nine (21%) had histologic responses. Mean serum alpha-tocopherol levels were 16.1 micrograms/mL at baseline and increased to 34.29 micrograms/mL after 24 weeks of treatment. Patient-recorded drug calendars, as well as serum drug levels, indicated excellent patient compliance; an average of 95% of the prescribed pills were taken. Treatment was extremely well tolerated; no grade 3 or 4 toxic effects were reported. Administration of alpha-tocopherol resulted in both clinical and histologic responses in premalignant leukoplakia lesions. The study also demonstrated that chemoprevention trials can be performed through the CCOP. The major problems were that a high percentage of patients were not assessable for response, some patients withdrew because expenses were not reimbursable, and there was limited participation within the CCOP network. These problems may reflect difficulties inherent in the implementation of multi-institutional chemoprevention trials. The efficacy of alpha-tocopherol alone and in combination with other chemopreventive agents for carcinogenesis in the upper aerodigestive tract should be explored in future trials.


Study of the Therapeutic Efficiency of Transduced Olfactory Ensheathing Cells in Spinal Cord Cysts.
Posttraumatic spinal cord cysts are difficult to treat with medication and surgery. Gene-cell therapy is a promising area of treatment for such patients. However, optimal gene-cell construct for this therapy has not been developed. We investigated the therapeutic efficiency of human olfactory ensheathing cells (OECs) transduced by adenoviral vector encoding the mature form of brain-derived neurotrophic factor (mBDNF) in spinal cord cysts. The adenoviral vectors Ad5/35-CAG-mBDNF and Ad5/35-CAG-Fluc were constructed. Spinal cysts were modeled in female Wistar rats. We selected animals at the early and intermediate stages of recovery with scores to 13 according to the Basso, Beattie and Bresnahan (BBB) scale. The efficiency of therapy was evaluated by BBB tests. No cytotoxicity was detected using the Resazurin/AlamarBlue assay for both vectors at multiplicity of infection (MOIs) of 1, 5, and 25. There was an increase in the proliferation of cells treated with Ad5/35-CAG-mBDNF at MOIs of 5 and 25. The hind limb mobility after the transplantation of Ad5/35-CAG-mBDNF- and Ad5/35-CAG-Fluc-transduced human OECs and nontransduced OECs had approximately the same tendency to improve. Cyst reduction was observed with the transplantation of all the samples. Although Ad5/35-CAG-mBDNF-transduced OECs had high BDNF expression levels in vitro, these cells lacked positive effect in vivo because they did not exhibit significant effect concerning functional test when comparing the groups that received the same numbers of OECs. The therapeutic efficiency of transduced OECs appears to be due to the cell component. The autological and tissue-specific human OECs are promising for the personalized cell therapy. It is extremely important to test new gene-cell constructs based on these cells for further clinical use.


Young children's appreciation of the mental impact of their communicative signals.
This work addresses whether 30-month-olds appreciate that their communicative signals are being understood (or not) by another person. Infants produce a range of behaviors, such as repairing their failed signals, that have been construed as evidence that they have an implicit theory of mind. Such behavior could be interpreted as attempts to obtain some desired goal rather than as attempts to gain listener understanding. This study was designed to separate listener comprehension from obtaining a material goal. In 4 conditions, children either did or did not get what they wanted and the experimenter understood or misunderstood their request. As predicted, children clarified their signal more when the experimenter misunderstood compared to when she understood. Regardless of whether young children achieved their overt goal, they engaged in behaviors to ensure their communicative act had been understood.


Cytocompatibility and response of osteoblastic-like cells to starch-based polymers: effect of several additives and processing conditions.
This work reports on the biocompatibility evaluation of new biodegradable starch-based polymers that are under consideration for use in orthopaedic temporary applications and as tissue engineering scaffolds. It has been shown in previous works that by using these polymers it is both possible to produce polymer/hydroxyapatite (HA) composites (with or without the use of coupling agents) with mechanical properties matching those of the human bone, and to obtain 3D structures generated by solid blowing agents, that are suitable for tissue engineering applications. This study was focused on establishing the influence of several additives (ceramic fillers, blowing agents and coupling agents) and processing methods/conditions on the biocompatibility of the materials described above. The cytotoxicity of the materials was evaluated using cell culture methods, according to ISO/EN 109935 guidelines. A cell suspension of human osteosarcoma cells (HOS) was also seeded on a blend of corn starch with ethylene vinyl alcohol (SEVA-C) and on SEVA-C/HA composites, in order to have a preliminary indication on cell adhesion and proliferation on the materials surface. In general, the obtained results show that all the different materials based on SEVA-C, (which are being investigated for use in several biomedical applications), as well as all the additives (including the novel coupling agents) and different processing methods required to obtain the different properties/products, can be used without inducing a cytotoxic behaviour to the developed biomaterials.


Tacrolimus: a review of its use for the management of dermatoses.
The newly developed immunomodulator tacrolimus (FK506) is the first of a new class of agents that have enormous potential to change the way that dermatoses are treated and managed. Tacrolimus has been found to be active in a topical formulation with the latter exerting its effects by acting on the signal transduction pathways inside T cells and inhibiting gene transcription. The result is decreased responsiveness of T cells to antigens. Percutaneous absorption of tacrolimus is higher in diseased skin as opposed to healthy skin and, therefore, the drug will be taken in at progressively lower quantities as lesions heal. There is limited systemic absorption of tacrolimus over the course of therapy. The most extensive experience with tacrolimus has been in treating atopic dermatitis. In numerous trials, tacrolimus ointment 0.03-0.3% has shown to be effective in reducing the symptoms and severity of atopic dermatitis in adults and the paediatric population. Furthermore, there have been no significant toxic effects associated with topical therapy with tacrolimus. The most common complaint is that of local irritation after applying the ointment. This is generally transient and the patient is able to continue with therapy. The other dermatoses where tacrolimus has been used include contact dermatitis, psoriasis and pyoderma gangrenosum.


[New morpho-functional rehabilitation methods in cleft lip and palate].
The interdisciplinary, complex therapeutic protocol of the cleft lip and palate patients, applied in the Clinic of Cranio-Maxillo-Facial Surgery of "I. Haţieganu" University of Medicine and Pharmacy Cluj-Napoca, involves the morphologic reconstruction as well as the functional rehabilitation. Functional rehabilitation is the aspect, which gives the esthetics, social and familial integration of the patient, offering good quality of life. In the current study, a new method and concept of improving the phonetic function in the primary and secondary surgical steps, with the effect on muscle and bone, is presented. The new surgical techniques used comprise of the surgery of the levator veli palatini using the method designed by Sader, and bone distraction, during the same surgical procedure. The assessment of the phonetic results was performed using the NARSOM test. Following up the results of the techniques mentioned above, we consider that they improve extremely well the morphological status, while giving a functional and physiological support to the patient. Thus, they offer optimal conditions for the future progress of functional rehabilitation using specific speech therapy methods.


Can metal-organic framework materials play a useful role in large-scale carbon dioxide separations?
Metal-organic frameworks (MOFs) are a fascinating class of crystalline nanoporous materials that can be synthesized with a diverse range of pore dimensions, topologies, and chemical functionality. As with other well-known nanoporous materials, such as activated carbon and zeolites, MOFs have potential uses in a range of chemical separation applications because of the possibility of selective adsorption and diffusion of molecules in their pores. We review the current state of knowledge surrounding the possibility of using MOFs in large-scale carbon dioxide separations. There are reasons to be optimistic that MOFs may make useful contributions to this important problem, but there are several critical issues for which only very limited information is available. By identifying these issues, we provide what we hope is a path forward to definitively answering the question posed in our title.


Reconstitution of hematopoiesis after bone marrow purging with ricin A chain immunotoxin.
Bone marrow cells from healthy individuals were treated with an antihuman T cell immunotoxin (IT101). The treated marrow cells were cultured for multilineage hematopoietic colonies (CFU-GEMMT) containing various myeloid cell lineages and T lymphocytes, erythroid colonies (BFU-E), and granulocytic colonies (CFU-C). Optimal conditions were defined for the elimination of clonogenic human T leukemic cells artificially admixed with bone marrow cells. Marrow purging with IT101 led to the restoration of hematopoietic colony formation which was abolished in the presence of T leukemic cells. Mixed colonies grown from bone marrow treated with IT101 contained cells that reacted with monoclonal anti-T-cell antibodies. This suggests that pluripotent stem cells are not affected by marrow IT101 purging and may be able to regenerate lymphoid as well as myeloid lineages.


A periodic pattern of mRNA secondary structure created by the genetic code.
Single-stranded mRNA molecules form secondary structures through complementary self-interactions. Several hypotheses have been proposed on the relationship between the nucleotide sequence, encoded amino acid sequence and mRNA secondary structure. We performed the first transcriptome-wide in silico analysis of the human and mouse mRNA foldings and found a pronounced periodic pattern of nucleotide involvement in mRNA secondary structure. We show that this pattern is created by the structure of the genetic code, and the dinucleotide relative abundances are important for the maintenance of mRNA secondary structure. Although synonymous codon usage contributes to this pattern, it is intrinsic to the structure of the genetic code and manifests itself even in the absence of synonymous codon usage bias at the 4-fold degenerate sites. While all codon sites are important for the maintenance of mRNA secondary structure, degeneracy of the code allows regulation of stability and periodicity of mRNA secondary structure. We demonstrate that the third degenerate codon sites contribute most strongly to mRNA stability. These results convincingly support the hypothesis that redundancies in the genetic code allow transcripts to satisfy requirements for both protein structure and RNA structure. Our data show that selection may be operating on synonymous codons to maintain a more stable and ordered mRNA secondary structure, which is likely to be important for transcript stability and translation. We also demonstrate that functional domains of the mRNA [5'-untranslated region (5'-UTR), CDS and 3'-UTR] preferentially fold onto themselves, while the start codon and stop codon regions are characterized by relaxed secondary structures, which may facilitate initiation and termination of translation.


High-efficiency second-harmonic generation in coupled nano Fabry-Perot thin resonators.
In this paper we experimentally demonstrate second-harmonic generation (SHG) enhancement in thin 1D periodic plasmonic nanostructures on GaAs in the infrared spectral range. Due to the properly designed coupling of horizontal Fabry-Perot nanoresonators that occurs inside these structures, the obtained conversion efficiencies go up to the 10-7 W-1 range. Moreover, we demonstrate that the engineering of the plasmonic nanoantenna dimensions on the same GaAs layer can lead to SHG enhancement for pump wavelengths ranging from 2.8 µm to 3.3 µm.


Negativity, emotionality and populist rhetoric in election campaigns worldwide, and their effects on media attention and electoral success.
Very little is known in broad comparative terms about the nature and content of election campaigns. In this article, we present the first systematic and comparative assessment of the electoral campaigns of candidates having competed in elections across the world along three dimensions: negative campaigning, emotional campaigning and populist rhetoric. We do so by introducing a new dataset, based on expert judgements, that allows us to retrace the content of campaigns of 97 candidates having competed in 43 elections worldwide between 2016 and 2018. To put the importance of these three dimensions of electoral campaigns into perspective, we comparatively assess the extent to which these three dimensions are more or less likely to capture the attention of news media and to determine the electoral fate of those who rely on them. Our analyses reveal that negativity and emotionality significantly and substantially drive media coverage and electoral results: more positive and enthusiasm-based campaigns increase media attention, but so do campaigns based on personal attacks and fear appeals, especially during presidential elections and when the number of competing candidates is lower. Looking at electoral success, negativity backlashes overall, and yet personal attacks can be used successfully to increase the chances of an electoral victory. Furthermore, both appeals to enthusiasm (but not when a lot of candidates compete) and fear (especially in presidential elections) work as intended to capture the attention of the public and transform it into better electoral fortunes. We also discuss the results of a case study of the 2017 French presidential election, where we compare the campaigns of four leading candidates (Emmanuel Macron, Marine Le Pen, François Fillon and Jean-Luc Mélenchon); results of the case study offer interesting insights to understand the general trends, and beyond.


Coping with parental cancer: web-based peer support in children.
To investigate the use and content of web-based peer support in children coping with parental cancer. In children aged above 12 years, 158 forum discussions on the Dutch website www.kankerspoken.nl in a time-period of 3 months were investigated. Age, gender, number of discussions, participation and main activities on the website were quantitatively assessed. Contents of the discussions were qualitatively analyzed. In total, 129 children and 8 adults participated on the website with an average age of 15.3 years. The majority was female (80%). On average, a child was on-line for 3 days and participated in 4 to 5 forum discussions. Main activities on the website were sharing personal experience, providing encouragement/support, providing and seeking information or advice and seeking contact outside of the website. Qualitative content analysis revealed that children regularly faced emotional problems and experienced a lack of understanding and communication in their direct environment. In dealing with parental cancer, children experience a variety of difficulties. This study offers a window into the use of web-based peer support by children dealing with parental cancer.


CD4 positive peripheral T cells from patients with systemic lupus erythematosus (SLE) are clonally expanded.
T cell activation was analysed in peripheral CD4+ T cells from both systemic lupus erythematosus (SLE) patients with active and inactive disease as well as in normal healthy donors (NHD) to investigate the involvement of CD4+ T cells in the etiopathogenesis of SLE. CD4+ T cell receptor (TCR) beta-chain transcripts, containing the complementarity determining region 3 (CDR3), were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and analysed by high-resolution polyacrylamide gel electrophoresis. In addition the CDR3 of both clonally activated as well as heterogeneous Vbeta families from SLE patients were analysed at the molecular level. We observed a restricted CDR3 length polymorphism in peripheral CD4+ T cells from SLE patients compared with NHD, more pronounced in patients with high disease activity. Furthermore, in some Vbeta families single peaks in the histogram indicated nearly monoclonal T cell expansion. Sequencing of selected TCR beta-chains revealed a increased content of acidic amino acids in the CDR3 encoded by either proximal Jbeta elements or N nucleotides. We conclude that CD4+ T cells from peripheral blood of SLE patients display features of a secondary antigen driven immune response. The bias of the CDR3 towards acidic amino acids suggests the involvement of positively charged antigens.


A Phenomenological Study of Nurses' Experience in Caring for COVID-19 Patients.
This study aimed to understand and describe the experiences of nurses who cared for patients with COVID-19. A descriptive phenomenological approach was used to collect data from individual in-depth interviews with 14 nurses, from 20 October 2020 to 15 January 2021. Data were analyzed using the phenomenological method of Colaizzi. Five theme clusters emerged from the analysis: (1) nurses struggling under the weight of dealing with infectious disease, (2) challenges added to difficult caring, (3) double suffering from patient care, (4) support for caring, and (5) expectations for post-COVID-19 life. The findings of this study are useful primary data for developing appropriate measures for health professionals' wellbeing during outbreaks of infectious diseases. Specifically, as nurses in this study struggled with mental as well as physical difficulties, it is suggested that future studies develop and apply mental health recovery programs for them. To be prepared for future infectious diseases and contribute to patient care, policymakers should improve the work environment, through various means, such as nurses' practice environment management and incentives.


Embryonic stem cell secreted factors decrease invasiveness of triple-negative breast cancer cells through regulome modulation.
Stem cell microenvironments decrease the invasiveness of cancer cells, and elucidating the mechanisms associated with disease regression could further the development of targeted therapies for aggressive cancer subtypes. To this end, we applied an emerging technology, TRanscriptional Activity CEll aRray (TRACER), to investigate the reprogramming of triple-negative breast cancer (TNBC) cells in conditions that promoted a less aggressive phenotype. The repressive environment was established through exposure to mouse embryonic stem cell conditioned media (mESC CM). Assessment of carcinogenic phenotypes indicated that mESC CM exposure decreased proliferation, invasion, migration, and stemness in TNBC cells. Protein expression analysis revealed that mESC CM exposure increased expression of the epithelial protein E-cadherin and decreased the mesenchymal protein MMP9. Gene expression analysis showed that mESC CM decreased epithelial to mesenchymal transition (EMT) markers fibronectin, vimentin, and Snail. Over a period of 6 d, TRACER quantified changes in activity of 11 transcription factors (TFs) associated with oncogenic progression. The EMT profile was decreased in association with the activity of 7 TFs (Smad3, NF-κΒ, MEF2, GATA, Hif1, Sp1, and RXR). Further examination of Smad3 and GATA expression and phosphorylation revealed that mESC CM exposure decreased noncanonical Smad3 phosphorylation and Smad3-mediated gene expression, increased GATA3 expression and phosphorylation, and resulted in a synergistic decrease in migration of GATA3 overexpressing MDA-MB-231 cells. Collectively, the application of TRACER to examine TF activity associated with the transition of cancer cells to a less aggressive phenotype, as directed by mESC CM, identified novel mechanistic events linking the embryonic microenvironment to both favorable changes and cellular plasticity in TNBC cell phenotypes.


Phenolic compounds and furanic derivatives in the characterization and quality control of Brandy de Jerez.
This article shows the results obtained in the study of the extraction profiles from oak wood to distillate of several compounds, low molecular weight phenolics, and furanic derivatives, and the relationship of their contents with those found in commercial sherry brandies and other aged distillates of different geographical origin, in order to research the utility of these analytical variables for explaining the highly specific character of Brandy de Jerez. Using multivariate statistic techniques, the aging system (static by anadas, or dynamic, well known as Soleras y Criaderas) has been confirmed as having a great influence on the analytical profile of aged distillates (discrimination is up to 100%). Differences between commercial brandies and those aged experimentally of equivalent average age have also been confirmed. The Solera Gran Reserva Brandies de Jerez show a clear differentiation from the rest of the distillates of different origin (discrimination is up to 80%), indicating their highly specific character.


[Grain-Moxibustion may Protect Myocardium by Reducing Oxidative Stress in Doxorubicin-induced Cardiomyopathy Rats].
To observe the effectiveness of grain-moxibustion in resisting oxidative stress in doxorubicin (DOX)-induced cardiomyopathy rats. Sixty Sprague-Dawley (SD) rats were randomly divided into blank control group (blank group), cardiomyopathy model (model) group and grain-moxibustion (moxibustion) group, with 20 rats in each one. The cardiomyopathy model was established by intraperitoneal injection of DOX (0.5 mg/100 g), once a week for 4 weeks. Grain-moxibustion was applied to "Guanyuan" (CV 4) and "Juque" (CV 14) for 5 cones, once daily for 4 weeks except the Sundays. The rats' heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), left ventricular pressure maximum rising rate (+dp/dtmax), left ventricular pressure maximum decline rate (-dp/dtmax), left ventricular pressure change time (t-dp/dtmax) were detected to evaluate the cardiac function by using a physiological signal acquisition-analysis system. The pathological changes of the myocardium were observed by optical microscopy after H.E. staining. The activity of serum lactate dehydrogenase(LDH), creatine kinase(CK) and myocardial superoxide dismutase (SOD), and myocardial malondialdehyde (MDA) and serum cardiac troponin Ⅰ(cTnⅠ) contents were assayed by enzyme-linked immuno sorbent assay kit (ELISA). Following modeling, the HR, LVSP, +dp/dtmax, -dp/dtmax, and myocardial SOD activity were significantly down-regulated (P<0.05, P<0.01), while the LVDP, t-dp/dtmax, serum LDH and CK activity and cTnⅠ content, as well as myocardial MDA content were considerably increased in comparison with the blank group (P<0.05, P<0.01). After moxibustion intervention, the decreased HR, LVSP, +dp/dtmax, -dp/dtmax, and myocardial SOD activity levels and the increased LVDP, t-dp/dtmax, serum LDH and CK activity and cTnⅠ content, as well as myocardial MDA content were remarkably suppressed in comparison with the model group (P<0.05, P<0.01). Grain-moxibustion can significantly improve the left ventricular function, increase heart rate in cardiomyopathy rats, which may be associated with its effects in reducing myocardial oxidative stress damage by down-regulating the content of MDA and up-regulating SOD activity in the heart.


The Manchester Colour Wheel: enhancing its utility.
The Manchester Colour Wheel was developed to investigate the role of colour in the perception of illness in gastroenterology. During validation it was found that positive, neutral, or negative connotations of the shade of a colour were more important than the colour itself. However, when asked to relate mood to a colour, the response rate was greater in individuals with mood disorders than healthy controls. This study assessed whether response rate could be made more uniform by changing the wording of the question. Mood/colour choice was compared, using two slightly different questions, in 105 and 203 healthy volunteers, resulting in response rates of 39% and 95% respectively, with the latter not associated with increased false positive responses. These results show that adjustment of the wording of a mood-related question may allow equal response rates irrespective of the mood status of participants.


Antifibrotic effects of total or partial application of amniotic membrane in hepatic fibrosis.
Liver fibrosis is the final common pathway of chronic liver diseases, having cirrhosis as a possible progression, which has liver transplantation as the only effective treatment. Human amniotic membrane represents a potential strategy as a therapy for liver fibrosis, due to its anti-inflammatory, anti-fibrotic and immunomodulatory properties. The aim of this study was to evaluate amniotic membrane effects as a treatment for hepatic fibrosis induced in rats by bile duct ligation (BDL), verifying alterations between two different forms of amniotic membrane application, around all the lobes of the liver and around only one lobe of the liver. Two weeks after inducing fibrosis, an amniotic membrane fragment was applied to the surface of the liver, covering it either totally or partially. Four weeks later, the animals were euthanized and liver samples were collected. Histopathological and quantitative analyses demonstrated fibrosis severity decrease and an extremely significant reduction in the deposition of collagen in the groups treated with amniotic membrane, particularly when the amniotic membrane was applied in only one liver lobe. It is concluded that the amniotic membrane acted on the repair of liver fibrosis in both modes of application, with the application of the amniotic membrane around only one hepatic lobe being more effective in reducing the severity / extent of fibrosis.


[Macroprolactinemia, a benign form of hyperprolactinemia].
In a 34-year-old woman with primary subfertility, a strongly increased serum concentration of prolactin was found in combination with normal levels of oestradiol, which is an indication for the presence of prolactin forms without clinical effect. She appeared to have macroprolactinaemia, i.e. the presence of circulating large forms of prolactin (up to > 100 kDa), which may be detected by the immunoassays currently used. They give no clinical signs or symptoms. Diagnosing macroprolactinaemia means that further diagnostic tests for hypopituitarism abnormalities using MRI need not be carried out and unjustified treatment of otherwise healthy persons may be prevented.


The Isolation and Partial Characterization of the Lipopolysaccharides from Several Rhizobium trifolii Mutants Affected in Root Hair Infection.
The lipopolysaccharides (LPSs) from Rhizobium trifolii ANU843 and several transposon (Tn5) symbiotic mutants derived from ANU843 were isolated and partially characterized. The mutant strains are unable to induce normal root hair curling (Hac- phenotype) or nodulation (Nod-phenotype) in clover plants. The LPSs from the parent and mutants are very similar in composition. Analysis by PAGE shows that the LPSs consist of higher and lower molecular weight forms. The higher molecular weight form of the LPSs exists in several aggregation states when PAGE is done in 0.1% SDS but collapses into a single band when PAGE is done in 0.5% SDS. Mild acid hydrolysis of all the LPSs releases two polysaccharides, PS1 and PS2. Immunoblots of the PAGE gels and enzyme linked immunosorbant assay inhibition assays show that the PS1 fractions contain the immunodominant sites of the LPSs and that these sites are present in the higher molecular weight form of the LPSs. All the PS1 fractions contain methylated sugars, 2-amino-2,6-dideoxyhexose, heptose, glucuronic acid, and 2-keto-3-deoxyoctonic acid (KDO). All the PS2 fractions contain galacturonic acid, mannose, galactose, and KDO. The PS2 fractions have a molecular weight of about 700. The KDO is present at the reducing end of both the PS1 and the PS2 fractions. The PS1 and PS2 fractions from the mutants contain more glucose than these fractions from the parent. The LPS from a deletion mutant contains less acyl groups than the other LPSs. Immunoblots of the LPSs show that the parent and nod A mutant LPSs contain an additional antigenic band which is not observed in the other LPSs.


Development of a self-guided web-based exercise intervention (SPIN) to treat shoulder pain in people living with spinal cord injury: protocol of a mixed methods study.
Chronic shoulder pain is common after spinal cord injury (SCI) and limits community mobility. This leads to loss of independence and reduced quality of life. Evidence suggests that exercises can help reduce shoulder pain. However, cost, expertise and transport barriers frequently limit access to treatment services. The objective of this study is to develop an evidence-based, acceptable, usable and persuasive self-guided web-based exercise intervention to treat shoulder pain in people living with SCI. An iterative and phased person-based approach (PBA) will capture users' perspectives on usability and acceptability to develop guiding principles that will shape the design of the intervention. The intervention will be based on key elements identified through participant input and from evidence identified through systematic and narrative reviews, to ensure the intervention addresses participants' needs and increase the likelihood of uptake. The prototype will be iteratively refined through focus groups and think-aloud sessions. Review data will be synthesised drawing on systematic and narrative review conventions. Qualitative data will be analysed using conventional content analysis (planning phase) and directed content analysis (development phase) to inform intervention design and refinement. Ethical approval has been granted by the Auckland University of Technology Ethics Committee (AUTEC) in Auckland, New Zealand. The results of the study will be published in a peer-reviewed journal and presented at relevant national and international conferences. A summary of findings will be presented to key stakeholder groups. We will progress to a definitive trial should the findings from this intervention development study indicate the intervention is acceptable and usable.


Gender balance in an unprecedented time.
As the NHS responds to the ongoing COVID-19 pandemic, the strain is being felt across the entire workforce. Both direct effects of COVID-19 and the response to the crisis are unearthing a number of societal inequalities, not least, those relating to gender. The fact that women play a disproportionate role in frontline health and social care roles and perform the majority of caregiving responsibilities is more exposed than ever before. Concurrently, the underrepresentation of women in senior clinical and leadership roles is being brought into stark relief. Redressing gender imbalance across health and social care is vital if we are to translate experience and learnings from our frontline workforce into our national preparedness and response effort. It is also important as we continue to promote wider gender and health equity goals within society. While we focus on responding to the current situation, an opportunity arises for greater value to be assigned to frontline health and caregiver roles. We must raise the profile of women leaders who are taking a stand during this crisis and use this opportunity to ensure that our future health and social care leadership reflects the wider workforce and the population.


1550 nm high contrast grating VCSEL.
We demonstrate an electrically pumped high contrast grating (HCG) VCSEL operating at 1550 nm incorporating a proton implant-defined aperture. Output powers of >1 mW are obtained at room temperature under continuous wave operation. Devices operate continuous wave at temperatures exceeding 60 degrees C. The novel device design, which is grown in a single epitaxy step, may enable lower cost long wavelength VCSELs.


Bienzyme sensors based on novel polymethylferrocenyl dendrimers.
Amperometric bienzyme electrodes with horseradish peroxidase (HRP) and glucose oxidase (GOx) co-immobilized on polymethylferrocenyl dendrimers deposited onto platinum electrodes have been used for determination of the hydrogen peroxide produced by the oxidase during the enzymatic reaction. The redox dendrimers consist of flexible poly(propylenimine) dendrimer cores functionalised with octamethylferrocenyl units. The effects of dendrimer generation, the thickness of the dendrimer layer, substrate concentration, interferences, and reproducibility on the response of the sensors were investigated. The new bienzyme biosensors respond to substrate at work potential values between 200 and 50 mV (vs. SCE), have good sensitivity, and are resistant to interferences. Figure.


Higher subcortical and white matter cerebral blood flow in perinatally HIV-infected children.
This study aimed to evaluate cerebral blood flow (CBF) in pediatric human immunodeficiency virus (HIV)-infection, and its role in HIV-related cerebral injury and cognitive impairment.This cross-sectional observational study compared 28 perinatally HIV-infected children (8-18 years) to 34 healthy controls matched for age, sex, ethnicity, and socio-economic status. All participants underwent 3-Tesla magnetic resonance imaging, using arterial spin labeling to assess CBF in gray matter (GM), white matter (WM), basal ganglia, and thalamus. We used linear regression analysis to evaluate group differences and associations with HIV disease and treatment characteristics, macrostructural (volume loss, WM lesions) or microstructural injury (increased WM diffusivity, neurometabolite alterations), or poorer cognitive performance.HIV-infected children had higher CBF in WM (+10.2%; P = 0.042), caudate nucleus (+4.8%; P = 0.002), putamen (+3.6%; P = 0.017), nucleus accumbens (+3.9%; P = 0.031), and thalamus (+5.5%; P = 0.032). Thalamus CBF was highest in children with a Centers for Disease Control and Prevention stage B (Coef. = 6.45; P = 0.005) or C (Coef. = 8.52; P = 0.001) diagnosis. Lower GM CBF was associated with higher WM lesion volume in HIV-infected children (Coef. = -0.053; P = 0.001). No further associations with HIV-related cognitive impairment or cerebral injury were found.CBF was higher in WM, basal ganglia, and thalamus in combination antiretroviral therapy (cART)-treated perinatally HIV-infected children, but this was not associated with cerebral injury or cognitive impairment. HIV-infected children with lower GM CBF had a higher volume of WM lesions, which could reflect vascular disease as potential contributing factor to white matter injury. Lifelong exposure to HIV and cART in this population warrants longitudinal assessment of CBF and how it relates to (neuro)inflammation, vascular dysfunction, and cerebral injury in pediatric HIV.


Adaptive regulation of membrane lipids and fluidity during thermal acclimation in Tetrahymena.
The free-living eukaryotic protozoan Tetrahymena is a potentially useful model for the thermoadaptive membrane regulation because of easy growth in the axenic culture, systematic isolation of subcellular organelles, and quick response to temperature stress. Exposure of Tetrahymena cells to the cold temperature induces marked alterations in the lipid composition and the physical properties (fluidity) of various membranes. The increase in fatty acid unsaturation of membrane phospholipids is required to preserve the proper fluidity. In this homeoviscous adaptive response, acyl-CoA desaturase plays a pivotal role and its activity is regulated by induction of the enzyme via transcriptional activation.


Parathyroid hormone induction of rat interstitial collagenase mRNA in osteosarcoma cells is mediated through an AP-1-binding site.
Interstitial collagenase is secreted by the osteoblast in response to bone-resorbing agents. Previously, we cloned the rat interstitial collagenase cDNA from UMR 106-01 rat osteoblastic osteosarcoma cells. We demonstrated that induction of collagenase by PTH, a powerful resorbing agent, in UMR 106-01 cells is in part transcriptional. In the present study we isolate and characterize the rat interstitial collagenase gene. The gene consists of 10 exons and spans approximately 12 kbp. The major transcriptional start site, determined by primer extension analysis and confirmed by RNase protection assay, is 25 nucleotides upstream of the translational start site. The previously isolated cDNA was missing the 5'-untranslated sequence in addition to 17 nucleotides of the signal sequence of the preproenzyme; therefore, we also present these data. Chloramphenicol acetyl transferase (CAT) analyses were performed on the 5'-upstream region of the gene. These data indicate that PTH appears to mediate its effect through an AP-1 consensus-binding sequence (-51). Footprint analysis demonstrates protein binding to this site. Site-specific mutagenesis markedly decreased protein binding, which correlated directly with a decrease in CAT activation by PTH. Supershift data indicate that cAMP response element binding protein (CREB) is binding to this AP-1 consensus sequence. In addition we demonstrate that PTH induces phosphorylation of CREB.


Complications of stomas: their aetiology and management.
The formation of a stoma is an essential part of many colorectal operations. Despite the frequency with which these surgeries are performed and the number of specialists involved in stoma care, complications are still common. This article investigates the most common complications, explains the reasons for their occurrence and suggests potential management options. Common stoma complications were identified by the colorectal/ stoma clinical nurse specialist (CSCNS) and a literature search was performed using a variety of online databases, including Medline and CINAHL using the keywords stoma, complications, prolapse, ischaemia, retraction, hernia and stenosis. Articles used were selected on the basis of relevance to the topic. The commonest complications of stomas included skin irritation, prolapse, retraction, ischaemia, hernia and stenosis.


Assessment of exposure to and risk posed by toluene in Japanese residents: combining exposure from indoor and outdoor sources.
Toluene is a chemical substance whose release to the atmosphere is the largest among the pollutant release and transfer registers (PRTR) chemicals and is regarded as one of the major indoor air pollutants. We have developed a method of estimating the distribution of personal exposures of Japanese residents, combining exposure from indoor and outdoor sources. Personal exposure was divided into contributions of indoor and outdoor sources. Ambient toluene concentration was estimated for a 5 x 5 km square grid spatial resolution using the National Institute of Advanced Industrial Science and Technology-atmospheric dispersion model for exposure and risk assessment (AIST-ADMER) using PRTR emission data. The contribution of indoor sources was assumed to be the difference between indoor and outdoor concentrations, which was regarded to have a lognormal distribution. The health risk from toluene exposure in Japanese residents is expressed as the number of people whose personal exposure exceeded the reference values, which were set on the basis of a review of epidemiological studies. Finally, a risk-reduction strategy is suggested according to the proposed principle of risk management.


Globe fixation with homologous temporalis fascia transplant for treatment of restrictive esotropia strabismus: an interventional case report and review of the literature.
To report a case of fat adherence complication syndrome after pterygium surgery, sufficiently severe enough to create a recurring significant extraocular motility problem and its ultimate novel and successful management. A 75 year old man was referred with an acquired large angle esotropia after pterygium surgery. Multiple previous strabismus surgeries to relieve the esotropia had already been performed but failed. Bilateral poor vision obviated complaints of diplopia but his binocular visual field was halved and his vision overall and his motility vision was handicapped by this limited ocular motility in his right eye. We therefore utilized homologous adjacent temporalis fascia transplantation for re-fixation of his frozen esotropic globe in primary position. Result of Surgery: Not only was the esotropia resolved but he also developed and regained some degree of abduction in this eye. Homologous Temporalis fascia transplant can be used safely, for globe fixation in surgical treatment of severe restrictive strabismus.


Protective effect of taurine on sepsis‑induced lung injury via inhibiting the p38/MAPK signaling pathway.
Sepsis, a leading cause of acute lung injury (ALI), is characterized by an overwhelming systemic inflammatory response and widespread organ injury, particularly in the lungs. Taurine, an intracellular free amino acid, has been used for the treatment of various diseases, including lung injury; however, the underlying mechanisms are unclear. The present study aimed to investigate the protective effect of taurine on septic ALI and the underlying mechanism. A septic ALI model was established by performing cecal ligation and puncture (CLP) surgery on Sprague Dawley rats. Following successful model establishment, rats were treated with taurine. The results of hematoxylin and eosin, respiratory function detection, malondialdehyde level and superoxide dismutase activity determination and ELSIA demonstrated that taurine significantly alleviated lung injury, restored respiratory function, reduced oxidation and decreased the concentrations of inflammatory factors in CLP‑induced septic ALI model rats. In addition, compared with that in the ALI group, western blotting results indicated that taurine ameliorated lung epithelial injury by significantly increasing the expression levels of lung epithelial markers, E‑cadherin and occludin. The western blotting results demonstrated that, compared with the control group, the p38/MAPK and NF‑κB signaling pathways were significantly activated in CLP‑induced septic ALI model rats, but taurine significantly suppressed ALI‑mediated signaling pathway activation. To investigate the mechanism underlying taurine in the treatment of septic ALI, CLP‑induced septic ALI model rats were treated with an antagonist of the p38/MAPK signaling pathway (SB203580). The effects of SB203580 on CLP‑induced septic ALI model rats were similar to those of taurine. SB203580 significantly attenuated sepsis‑induced lung injury and increases in IL‑1β and TNF‑α concentrations in the lung tissue. In addition, SB203580 promoted restoration of the injured lung tissue and respiratory function in CLP‑induced septic ALI model rats. The western blotting results indicated that SB203580 significantly decreased the ratios of phosphorylated (p)‑p38/p38 and p‑p65/065, and increased the protein expression levels of E‑cadherin and occludin compared with those in the ALI group. In summary, the present study demonstrated that taurine alleviated sepsis‑induced lung injury, which was associated with suppression of the inflammatory response and oxidative stress via inhibiting the p38/MAPK signaling pathway. Therefore, the p38/MAPK signaling pathway may serve as a potential therapeutic target for the treatment of sepsis‑induced ALI.


Motor unit number estimation in evaluating disease progression in patients with amyotrophic lateral sclerosis.
We investigated the availability of motor unit number estimation (MUNE) as a quantitative method to assess the severity and clinical progression of amyotrophic lateral sclerosis (ALS). The 143 ALS patients were evaluated by statistical MUNE and the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R). By using mean values of MUNE according to disease duration, regression equation between mean MUNE and disease duration was presented as a formula. The individual MUNE ratio was calculated by dividing individual MUNE value by mean MUNE value. All patients were classified into 2 groups (MUNE ratio <1 vs. MUNE ratio >or=1) according to the MUNE ratio. Comparison between the 2 groups revealed that the patients in MUNE ratio <1 group or MUNE ratio >or=1 group were respectively assigned to rapid progression or slow progression. We recommended informative mean values of MUNE and best regression equation in ALS patients according to disease duration. These values allow us to evaluate the severity and rapidity of progression in ALS.


Self-Locked and Self-Cleaning Membranes for Efficient Removal of Insoluble and Soluble Organic Pollutants from Water.
A feasible and efficient membrane for long-term treatment of complex oily wastewater is especially in demand, but its development still remains a challenge because of serious membrane fouling and incomplete/destructive reclamation methods. Herein, an interpenetrating TiO2 nanorod-decorated membrane with self-locked and self-cleaning properties is rationally fabricated via coaxial electrospinning and hydrothermal synthesis. The self-locked membrane shows full reinstatement of the original state and exhibits satisfactory mechanical strength, superhydrophilicity, underwater superoleophobicity, and robust solvent resistance, which endow the membrane with successful separation for 16 types of highly emulsified oil-in-water emulsions (e.g., surfactant-free; anionic, cationic, and nonionic surfactant-stabilized). Moreover, successful sequencing treatment of soluble organic emulsions using the separated "bait-hook-destroy" strategy indicates that the pristine membrane can be used to treat multipollutant wastewater with various limits. Most importantly, the fouled membrane can easily be reinstated by light irradiation without reduction of both mechanical strength and separation performance. As a proof of concept, the as-synthesized membrane shows an ultrahigh flux over 5000 L m-2 h-1 with a removal efficiency of >99.92%. The present development would provide a highly efficient strategy for the fabrication of an inorganic-organic revivable electrospinning membrane for various applications.


Metabolic Bone Disease in Children with Intestinal Failure and Long-Term Parenteral Nutrition: A Systematic Review.
Metabolic bone disease (MBD) is a possible complication of intestinal failure (IF), with a multi-factorial pathogenesis. The reduction of bone density (BMD) may be radiologically evident before manifestation of clinical signs (bone pain, vertebral compression, and fractures). Diagnosis relies on dual-energy X-ray absorptiometry (DXA). Incidence and evolution of MBD are not homogeneously reported in children. The aim of this systematic review was to define the prevalence of MBD in IF children and to describe risk factors for its development. A comprehensive search of electronic bibliographic databases up to December 2021 was conducted. Randomized controlled trials; observational, cross-sectional, and retrospective studies; and case series published between 1970 and 2021 were included. Twenty observational studies (six case-control) were identified and mostly reported definitions of MBD based on DXA parameters. Although the prevalence and definition of MBD was largely heterogeneous, low BMD was found in up to 45% of IF children and correlated with age, growth failure, and specific IF etiologies. Data demonstrate that long-term follow-up with repeated DXA and calcium balance assessment is warranted in IF children even when PN dependence is resolved. Etiology and outcomes of MBD will be better defined by longitudinal prospective studies focused on prognosis and therapeutic perspectives.


Cervical degenerative changes in idiopathic scoliosis patients who underwent long fusion to the sacrum as adults: incidence, severity, and evolution.
To date, there have been no published studies of the degenerative changes in the cervical spine in adult idiopathic scoliosis patients with thoracic and lumbar curves severe enough to require major reconstructive surgery. The primary study group was 48 adult patients who had previously undergone a fusion from T10 or higher to the sacrum as an adult for idiopathic scoliosis. These were compared to 38 adults with unfused idiopathic scoliosis of 30 degrees -50 degrees and to 42 symptomatic adults presenting with cervical pain. Cervical degeneration was assessed using a new cervical degenerative index (CDI). The amount of degenerative change seen in the cervical spine in the long-fusion group was significantly higher at baseline (just prior to the fusion) than the two control populations and became much higher at a mean follow-up of 8.5 years. This unique subgroup of patients, those having fusion from the thoracic spine to the sacrum as adults for adolescent idiopathic scoliosis, had a high incidence and severity of degenerative changes in their cervical spine. Due to the presence of advanced cervical degenerative changes prior to the fusion, it is not possible to blame the fusion as the main cause for these findings. These changes are either related to the thoracic and lumbar deformities or are more likely due to this subgroup having a higher natural propensity for degenerative changes.


Adenosine analogues as selective inhibitors of glyceraldehyde-3-phosphate dehydrogenase of Trypanosomatidae via structure-based drug design.
In our continuation of the structure-based design of anti-trypanosomatid drugs, parasite-selective adenosine analogues were identified as low micromolar inhibitors of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Crystal structures of Trypanosoma brucei, Trypanosoma cruzi, Leishmania mexicana, and human GAPDH's provided details of how the adenosyl moiety of NAD(+) interacts with the proteins, and this facilitated the understanding of the relative affinities of a series of adenosine analogues for the various GAPDH's. From exploration of modifications of the naphthalenemethyl and benzamide substituents of a lead compound, N(6)-(1-naphthalenemethyl)-2'-deoxy-2'-(3-methoxybenzamido)adenosine (6e), N(6)-(substituted-naphthalenemethyl)-2'-deoxy-2'-(substituted-benzamido)adenosine analogues were investigated. N(6)-(1-Naphthalenemethyl)-2'-deoxy-2'-(3,5-dimethoxybenzamido)adenosine (6m), N(6)-[1-(3-hydroxynaphthalene)methyl]-2'-deoxy-2'-(3,5-dimethoxybenzamido)adenosine (7m), N(6)-[1-(3-methoxynaphthalene)methyl]-2'-deoxy-2'-(3,5-dimethoxybenzamido)adenosine (9m), N(6)-(2-naphthalenemethyl)-2'-deoxy-2'-(3-methoxybenzamido)adenosine (11e), and N(6)-(2-naphthalenemethyl)-2'-deoxy-2'-(3,5-dimethoxybenzamido)adenosine (11m) demonstrated a 2- to 3-fold improvement over 6e and a 7100- to 25000-fold improvement over the adenosine template. IC(50)'s of these compounds were in the range 2-12 microM for T. brucei, T. cruzi, and L. mexicana GAPDH's, and these compounds did not inhibit mammalian GAPDH when tested at their solubility limit. To explore more thoroughly the structure-activity relationships of this class of compounds, a library of 240 N(6)-(substituted)-2'-deoxy-2'-(amido)adenosine analogues was generated using parallel solution-phase synthesis with N(6) and C2' substituents chosen on the basis of computational docking scores. This resulted in the identification of 40 additional compounds that inhibit parasite GAPDH's in the low micromolar range. We also explored adenosine analogues containing 5'-amido substituents and found that 2',5'-dideoxy-2'-(3,5-dimethoxybenzamido)-5'-(diphenylacetamido)adenosine (49) displays an IC(50) of 60-100 microM against the three parasite GAPDH's.


Postoperative irradiation for pterygium: retrospective analysis of 1,253 patients from the Osaka University Hospital.
Irradiation of ocular pterygium is considered a valuable treatment supplementation after surgical therapy. Since prospective randomized trials are scare and only limited patient data are available, the aim of this study was to evaluate the patient population treated with fractioned 90Sr irradiation after surgical pterygium resection. Between September 1993 and March 2001, 1,147 patients with pterygium lesions (1,320 lesions) were treated surgically and with 90Sr postoperative beta-irradiation. A total dose of 30 Gy was used for patients treated within 48 h after surgery, while those treated>48 h postoperatively received a total dose of 35 Gy. A minimum follow-up period of 3 months was required for inclusion in the analysis, and 1,253 lesions were ultimately analyzed. Recurrence of the pterygium after postoperative 90Sr irradiation was observed in 97 of 1,253 cases (7.7%). Statistical analysis (uni- and multivariate) revealed, that male gender, younger age (<40 years), prior treatment (surgery and radiotherapy) and immediate irradiation (<2 h after surgery) were negative predictors for local recurrence. Temporary radiotherapy-induced side effects were observed in 15.2% of patients, including moderate conjunctivitis, local pain, visual disturbance and photophobia or an increase in tear flow. However, no long-term serious side effects were documented. 90Sr irradiation of pterygium after surgery represents a safe and effective treatment option to prevent disease recurrence. The data obtained in this study indicate that a certain interval after surgery might improve therapy outcome.


Serotonin syndrome.
Serotonin syndrome is a preventable, drug-related complication that results from increased brainstem serotonin activity, usually precipitated by the use of one or more serotonergic drugs. Its clinical presentation consists of autonomic dysfunction, alteration in mental status, and neuromuscular disorder. Early recognition and treatment is important, because this condition is potentially fatal. Management includes withdrawal of causative agents and supportive measures such as hemodynamic stabilization, sedation, temperature control, hydration, and monitoring for complications. Serotonin antagonists, specifically cyproheptadine, have been used, but the documented benefits are purely anecdotal.


A new species of Ptilomymar (Hymenoptera, Mymaridae) and a key to the described species.
Ptilomymar dianensis sp. n. (Hymenoptera, Mymaridae) from southwest China is described and illustrated. A key to the six described species is given. The type specimens are deposited in the insect collections of Northeast Forestry University, China.


Dementia associated with the antiphospholipid syndrome: clinical and radiological characteristics of 30 patients.
To analyse the clinical and radiological characteristics of patients with dementia associated with the antiphospholipid syndrome (APS). Twenty-five patients were identified by a computer-assisted (MEDLINE, National Library of Medicine, Bethesda, MD) search of the literature to locate all cases of dementia associated with APS published in English, Spanish and French from 1983 to 2003. Additionally, we included five patients from our clinics. There were 21 (70%) females and 9 (30%) males. The mean age of patients was 49+/-15 yr (range 16-79 yr). Fourteen (47%) of the patients suffered from primary APS, 9 (30%) had systemic lupus erythematosus and 7 (23%) had 'lupus-like' syndrome. Ten (33%) patients had Sneddon's syndrome and 2 (7%) had cerebral lesions described as Binswanger's disease. Other APS-related manifestations included thrombocytopenia in 12 (40%) patients, cerebrovascular accidents in 11 (37%), heart valve lesions in 8 (27%), deep vein thrombosis in 7 (28%), migraine in 7 (23%), seizures in 4 (13%); five of the 21 (24%) female patients had nine spontaneous abortions. Lupus anticoagulant was present in 21/29 (72%) patients and anticardiolipin antibodies were present in 24/29 (83%) patients. Cortical infarcts were found in 19 (63%) patients, subcortical infarcts in 9 (30%), basal ganglia infarcts in 7 (23%) and signs of cerebral atrophy in 11 (37%). Anticoagulation was used in 14/25 (56%) patients, steroids in 12/25 (48%), aspirin in 6/25 (24%) and dypiridamole in 5/25 (20%). Dementia is an unusual manifestation of APS but one which has a high disability impact in a patient's daily life. In order to prevent these consequences, an echocardiographic and cerebral CT or MRI evaluation are recommended in all patients with APS. Furthermore, ruling out APS should be recommended in the clinical approach to dementia, especially in young patients.


Accuracy of ultrasound measurements of female pelvic organs.
Uterine size, endometrial thickness and ovarian volume were measured ultrasonically and the results compared with caliper measurements made shortly afterwards at the time of total hysterectomy and bilateral salpingo-oophorectomy. The results establish the validity of ultrasound measurements. Histological studies also confirmed the diagnosis made with ultrasound of polycystic ovaries in women complaining of pain due to pelvic congestion.


Prognostic factors in carcinoma of the larynx: relevance of DNA ploidy, S-fractions and localization of the tumour.
The influence of the cell cycle profile and the site of the primary tumour on the overall survival were examined in 36 patients with squamous cell carcinoma of the larynx. DNA ploidy (p = 0.0091), the overall proliferative activity (p = 0.0001), the overall proliferative activity of diploid tumour cells (p = 0.0017) and primary tumour site (p = 0.0008) were found to be significant single prognostic factors of the overall survival. Multivariate analysis showed that only the overall proliferative activity was prognostically significant (p = 0.013). The results of the study show that the supraglottic site of the tumours correlates significantly with DNA ploidy (p = 0.0334) and the overall proliferative activity of tumour cells (p = 0.0159), whereas the correlation with proliferative activity of diploid tumour cells (p = 0.1416) has not been confirmed by this study. Glottic tumours showed a prognostically significant correlation with the overall proliferative activity (p = 0.0037) and proliferative activity of diploid tumour (p = 0.0054). Such a prognostic correlation was not found for DNA ploidy (p = 0.6542).


Current tobacco use policies in Nebraska public schools.
A critical effort to reduce the harmful effects of tobacco is to promote tobacco abstinence among the nation's adolescent population. In this regard, the message of tobacco tolerance within the education system of the State of Nebraska was examined. Although the majority of schools surveyed have an encouraging policy regarding student smoking, it has not yet been universally implemented. In addition, the tobacco-use policies for non-students within public school buildings is concerning. The Nebraska Indoor Clean Air Act and the recent Environmental Protection Agency warning on second-hand smoke provides a framework for change. Health care providers can be proactive in encouraging their school districts to promote the goal of a Tobacco-Free Nebraska.


Cloning, characterization and expression of an alpha-amylase gene from Streptomyces griseus IMRU3570.
A gene, amy, encoding an alpha-amylase, was cloned on a 4.8 kb Sau3A fragment from the DNA of Streptomyces griseus IMRU3570. The gene was localized to a 2.27 kb fragment by subcloning and deletion mapping experiments. The gene contained an open reading frame (ORF) of 1698 nucleotides that encoded a protein of 566 amino acids with a deduced Mr of 59713 Da. Dot-blot analysis revealed that the copy number of the transcript in S. lividans transformed with the amy gene was 2.8-fold higher than in the donor S. griseus strain in good agreement with the proportionally higher secretion of amylase in S. lividans. A transcription initiation site was found approximately 64 bp upstream from the ATG translation start codon. The promoter of the amy gene was subcloned on a 290 bp HindIII--EcoRI fragment. Expression of a neomycin resistance gene from the amy promoter was negatively regulated by glucose. A 219 nucleotide fragment extending from the single BstEII site to the end of the amy gene was dispensable since active alpha-amylase was secreted after deletion of this region and coupling of a TGA translation stop codon.


Retinal Image Enhancement Using Cycle-Constraint Adversarial Network.
Retinal images are the most intuitive medical images for the diagnosis of fundus diseases. Low-quality retinal images cause difficulties in computer-aided diagnosis systems and the clinical diagnosis of ophthalmologists. The high quality of retinal images is an important basis of precision medicine in ophthalmology. In this study, we propose a retinal image enhancement method based on deep learning to enhance multiple low-quality retinal images. A generative adversarial network is employed to build a symmetrical network, and a convolutional block attention module is introduced to improve the feature extraction capability. The retinal images in our dataset are sorted into two sets according to their quality: low and high quality. Generators and discriminators alternately learn the features of low/high-quality retinal images without the need for paired images. We analyze the proposed method both qualitatively and quantitatively on public datasets and a private dataset. The study results demonstrate that the proposed method is superior to other advanced algorithms, especially in enhancing color-distorted retinal images. It also performs well in the task of retinal vessel segmentation. The proposed network effectively enhances low-quality retinal images, aiding ophthalmologists and enabling computer-aided diagnosis in pathological analysis. Our method enhances multiple types of low-quality retinal images using a deep learning network.


Current epidemiological status of schistosomiasis in the state of Pernambuco, Brazil.
Uncontrolled peripheral urbanisation coupled with environmental degradation has affected the status of schistosomiasis in Pernambuco (PE), Brazil. This endemic disease continues to perpetuate its transmission in rural areas and has also become a cause for concern in coastal towns of the state. The lack of basic infrastructure (sanitation and health programmes) to support the new urban areas leads to faecal contamination of natural aquatic environments, resulting in consequent infection of vector snails and the emergence of new sources of schistosomiasis transmission. In the present paper, we discuss the current epidemiological status of schistosomiasis in PE. We have consolidated and analysed information from parasitological, malacological and morbidity surveys undertaken by the group of researchers at the Laboratory of Schistosomiasis, Centro de Pesquisas Aggeu Magalhães-Fiocruz. The results of our analysis show: (i) the maintenance of the levels of schistosomiasis in the rural Zona da Mata, PE, (ii) the record of the human cases of schistosomiasis and the foci of infected snails detected along the coast of PE through 2007, (iii) the high record of the severe clinical form of schistosomiasis in the metropolitan region of Recife (RMR) and (iv) new breeding sites of schistosomiasis vector snails that were identified in a 2008 survey covering the RMR and the coastal localities of PE.


Infraspecific variation of some brown Parmeliae (in Poland) - a comparison of ITS rDNA and non-molecular characters.
Infraspecific variation of the ITS rDNA region of some brown Parmeliae occurring in Poland is studied and compared with non-molecular characters. Haplotype networks are used to illustrate the variability within the species. Both newly-produced sequences from Central Europe and from all over the world, downloaded from the GenBank, are used. The number of haplotypes found for each taxon ranged from five in Melaneliastygia to 12 in Melaneliahepatizon and Montaneliadisjuncta; however, their numbers correlate with the number of specimens tested. New haplotypes for Melaneliaagnata, M.hepatizon and Cetrariacommixta are found. Based on our 169-sample dataset, we could not infer any geographical correlation, either locally or world-wide. Many of the analysed haplotypes were widely distributed and the same haplotype was often shared between temperate and polar populations. A comparison of molecular, morphological, anatomical and chemical characters also shows no correlation.


Effects of space flight on bone formation and resorption.
Samples of femurs and tibiae of male Wistar rats subjected to a 13 day space-flight on the biosatellite Cosmos 1887--were investigated and compared with vivarium and synchronous controls or immobilized rats, using histological and histomorphometric methods. 1. After flight in the metaphysis of bones the density and volume of the spongious trabeculae diminished significantly indicated by the Sv and Vv histomorphometric values and histological data comparing to the controls. In the diaphysis, the density of trabeculae decreased too. 2. In the flight group significant suppression of bone formation was determined by histological and histomorphometric (decrease of the OS, OB and OBI values) methods. 3. In the flight group according to the histological pictures the signs of bone resorption (increase of Hoswship's lacunae, osteoclastic activity, structural rarefication of spongious and cortical bones, osteon disintegration, osteocytic osteolysis) were revealed, which was substantiated by the histomorphometric results (increase of osteoclastic index: OCI). 4. Significant differences between flight and immobilized groups were not determined, except the osteoid value, which was increased in the case of immobilization. 5. Some histomorphometric values related to bone formation of synchronous control group showed close relationship rather to the flight group than to the vivarium control group.


Mice lacking Dad1, the defender against apoptotic death-1, express abnormal N-linked glycoproteins and undergo increased embryonic apoptosis.
Dad1 has been shown to play a role in preventing apoptotic cell death and in regulating levels of N-linked glycosylation in Saccharomyces cerevisiae and the BHK hamster cell line. To address the in vivo role of Dad1 in these processes during multicellular development, we have analyzed mice carrying a null allele for Dad1. Embryos homozygous for this mutation express abnormal N-glycosylated proteins and are developmentally delayed by embryonic day 7.5. Such mutants exhibit aberrant morphology, impaired mesodermal development, and increased levels of apoptosis in specific tissues. These defects culminate in homozygous embryos failing to turn the posterior axis and subsequent lethality by embryonic day 10.5. Thus, Dad1 is required for proper processing of N-linked glycoproteins and for certain cell survival in the mouse.


Modeling of elastic modulus evolution of cirrhotic human liver.
A micromechanics-based composite model is developed for the elastic behavior and its modulus evolution of cirrhotic human liver correlated with different pathological stages. Microstructurally, the cirrhotic liver is hypothesized to be pathologically elastic nodules embedded in the soft tissue matrix whose hyperelastic behavior is controlled by the Veronda-Westmann model. Under finite deformation, the total strain energy of the liver is collected through the combination of that in nodule particles and that in the tissue matrix. The overall constitutive relation of the pathological liver can further be established through the nonlinear hyperelasticity theory. Predictions of the elastic modulus and its pathological evolution are compared with available experimental data.


Detecting alcohol consumption as a cause of emergency general medical admissions.
In a general medical unit 27% of 104 admissions and 17% of bed occupancy were attributed to alcohol consumption, although only 10 of these 28 patients had classical alcohol-related conditions. Questioning on the amount of alcohol consumed was the most accurate method of screening for these patients. The brief MAST questionnaire, mean red cell volume, gamma-glutamyl transferase, aspartate transaminase and urate were all inadequate as screening tests. Only 13% of the admissions were defined as 'problem drinkers' on the brief MAST questionnaire, suggesting that harmful effects of alcohol are not confined to 'alcoholics'. Clinical suspicion and questions on the level of alcohol consumption are more efficient than questionnaire, biochemical or haematological screening tests in detecting alcohol-related medical problems.


Efficacy and safety of oral and transdermal hormonal replacement treatment containing levonorgestrel.
The oral combined formulation of levonorgestrel with estradiol valerate (LNG+EV) has demonstrated to be effective on some postmenopausal symptoms. The availability of a transdermal HRT in sequential formulation with 17-beta-estradiol plus levonorgestrel (TSE2+TSLNG) induced us to do this control-study with the aim to evaluate the efficacy and safety of both oral and transdermal treatments. At baseline, the psychological symptoms with the psychometric scale SCL-90, the bone resorption with the measurement of the urinary levels of pyridinoline and dexoxypirydinoline, and the insulin and lipid metabolism were assessed in 30 postmenopausal women (PMW) and in 18 premenopausal women. Then, the PMW women were randomly divided in three groups: group A (N=10) assumed EV+LNG, group B (N=10) did not assume any treatment, group C (N=10) was treated with TSE2+TSLNG. The length of the study was 12 months. The aforementioned assessments were repeated at different time-intervals up to the end of the study. The total score of SCL-90, the bone resorption, the levels of LDL-cholesterol, total-cholesterol and the parameters of insulin metabolism were higher in PMW than in premenopausal women. During the study, the SCL-90, the bone resorption, total-cholesterol, and LDL-cholesterol levels significantly decreased only in the groups A and C. By contrast, in the group B bone resorption significantly increased at the 12th month. During the treatments, insulin metabolism did not change in the groups A and B. In the group C the secretion of C-peptide and the C-peptide:insulin ratio after OGTT were significantly higher at the 12th month than before treatment. In all groups the endometrium thickness did not change during the study. A 12-month of either oral or transdermal HRT containing levonorgestrel seems to exert beneficial effects on the main postmenopausal symptoms without negative interferences on the endometrium.


Special Education Major or Attitudes to Predict Teachers' Self-Efficacy for Teaching in Inclusive Education.
This study aimed to determine the predictors for Saudi Arabian teachers' self-efficacy to work in inclusive education. Five independent variables were tested in this study: attitudes toward inclusive education, participants' educational major, having relative with disability, working with students with disability and gender. Further, predictors of teachers' attitudes toward inclusive education were examined. The sample was 185 elementary-school teachers in Saudi Arabia. The Arabic version of the Teacher Efficacy for Inclusive Practices scale was used to measure self-efficacy. To assess attitudes toward inclusion an Arabic version of the Sentiments, Attitudes, and Concerns about Inclusive Education Revised subscale was used. Results showed teacher attitude toward inclusion are strongly linked with teachers' self-efficacy to work in inclusive classrooms. Further, participants with a relative with a disability showed more positive attitudes for inclusive education. Levels of self-efficacy were unaffected by gender, having a special education degree, or having a relative with a disability. In sum, this study highlighted the importance of teachers' attitudes toward inclusive education as a main predictor of teachers' self-efficacy.


Interaction Effect of Awareness and Educational Attainment on the Benefits of Multicomponent Intervention for Persons with Mild Alzheimer's Disease.
The study investigated the effect of education on cognitive outcome following a multicomponent intervention program (MIP) for people with Alzheimer's disease (AD), also exploring the additional effect of level of awareness. Fifty-five participants with mild AD were randomized to an MIP (intervention group; IG) or a waiting-list (WL) group. They were further stratified into 4 groups by educational attainment (high vs. low) and level of awareness (aware [IGU-] vs. unaware [IGU+]). MIP efficacy in the different groups was measured using the mean change scores (MCSs) in the Cognitive subscale of Alzheimer's disease Assessment Scale, with pre- and post-treatment testing. A negative correlation was found between educational level and the MCS in the IG, whereas the correlation in the WL group was positive. Moreover, an interaction effect emerged between education and awareness. Here, in the group of aware individuals, those with high education benefited more from the intervention than those with low education. This difference was not observed in the unawareness group. Higher education may diminish the progression of cognitive decline after MIP, but this potentially depends on the level of awareness.


Maintenance carbon cycle in crassulacean Acid metabolism plant leaves : source and compartmentation of carbon for nocturnal malate synthesis.
The reciprocal relationship between diurnal changes in organic acid and storage carbohydrate was examined in the leaves of three Crassulacean acid metabolism plants. It was found that depletion of leaf hexoses at night was sufficient to account quantitatively for increase in malate in Ananas comosus but not in Sedum telephium or Kalanchoë daigremontiana. Fructose and to a lesser extent glucose underwent the largest changes. Glucose levels in S. telephium leaves oscillated diurnally but were not reciprocally related to malate fluctuations.Analysis of isolated protoplasts and vacuoles from leaves of A. comosus and S. telephium revealed that vacuoles contain a large percentage (>50%) of the protoplast glucose, fructose and malate, citrate, isocitrate, ascorbate and succinate. Sucrose, a major constituent of intact leaves, was not detectable or was at extremely low levels in protoplasts and vacuoles from both plants.In isolated vacuoles from both A. comosus and S. telephium, hexose levels decreased at night at the same time malate increased. Only in A. comosus, however, could hexose metabolism account for a significant amount of the nocturnal increase in malate. We conclude that, in A. comosus, soluble sugars are part of the daily maintenance carbon cycle and that the vacuole plays a dynamic role in the diurnal carbon assimilation cycle of this Crassulacean acid metabolism plant.


Electromechanical Characteristics by a Vertical Flip of C70 Fullerene Prolate Spheroid in a Single-Electron Transistor: Hybrid Density Functional Methods.
In this study, the B3LYP hybrid density functional theory was used to investigate the electromechanical characteristics of C70 fullerene with and without point charges to model the effect of the surface of the gate electrode in a C70 single-electron transistor (SET). To understand electron tunneling through C70 fullerene species in a single-C70 transistor, descriptors of geometrical atomic structures and frontier molecular orbitals were analyzed. The findings regarding the node planes of the lowest unoccupied molecular orbitals (LUMOs) of C70 and both the highest occupied molecular orbitals (HOMOs) and the LUMO of the C70 anion suggest that electron tunneling of pristine C70 prolate spheroidal fullerene could be better in the major axis orientation when facing the gate electrode than in the major (longer) axis orientation when facing the Au source and drain electrodes. In addition, we explored the effect on the geometrical atomic structure of C70 by a single-electron addition, in which the maximum change for the distance between two carbon sites of C70 is 0.02 Å.


Pharmacokinetics and biliary excretion of mitoxantrone in rats.
The objective of this investigation was to compare the observed biliary clearance (CL(b)) and % of dose excreted in the bile (PD(b)) of mitoxantrone with the predicted values obtained from quantitative structure pharmacokinetic relationship (QSPKR) models. Blood and bile samples were collected from bile duct cannulated rats after an intravenous bolus dose of 0.5 or 2 mg/kg mitoxantrone, and the concentrations were measured by HPLC. Mitoxantrone plasma concentrations exhibited a tri-exponential profile with systemic clearance of 118 +/- 6.8 mL/min/kg. After dosing, 6.08 +/- 2.32% and 5.69 +/- 0.59% of the dose were excreted into bile in unchanged form after a 3-h collection. CL(b) was 7.20 +/- 4.54 and 7.46 +/- 0.62 mL/min/kg after the two doses. With the co-administration of 10 mg/kg GF-120918, a P-glycoprotein and BCRP inhibitor, PD(b) was reduced to 0.69 +/- 0.07%, suggesting that BCRP or P-glycoprotein may play an important role in the biliary elimination of mitoxantrone. Using QSPKR models developed for the biliary excretion of cations/neutral compounds in rats, CL(b) and PD(b) of mitoxantrone were predicted as 5.18 mL/min/kg and 7.21%, respectively, suggesting that the models could be used to predict the biliary excretion of mitoxantrone.


Fate of fumonisins B1 and B2 in steeped corn kernels.
Corn kernels naturally contaminated with fumonisins B1 and B2 were steeped by dipping the whole kernels in either water or a 0.3% solution of sodium bisulphite (pH = 5.7) for 6, 12, 24, 36 and 48 h. The toxin content of both the solid and the liquid were analysed for each time period. A different rate of interchange between the solid matrix and the water solution was found for FB1 and FB2 and some differences were found in the fate of both fumonisins between the two steeping systems studied. In addition, a preliminary study of the distribution of FB1 and FB2 between the germ and the remaining part of the kernel was carried out.


The nature of fatty acid modifies the equilibrium position in the esterification catalyzed by lipase.
The equilibrium position in lipase mediated esterification of various fatty acids and butanol was studied. The influence of the chain length and the presence of unsaturations in the fatty acids on the equilibrium position was measured and predicted. To predict equilibrium position the program TREP extended (TREPEX) based on the UNIFAC group contribution method was used. Using an equilibrium constant of 35, calculated on the basis of thermodynamic activities, the equilibrium position between butanol and saturated and/or unsaturated fatty acids with different chain lengths can be predicted. The ester mole fraction at equilibrium increases with the fatty acid chain length, and for fatty acids with the same carbon number, the highest values are found for unsaturated fatty acids. For reaction systems containing two saturated fatty acids, a slightly higher mole fraction is obtained for the fatty acid with the higher chain length, while for mixtures consisting of saturated and unsaturated fatty acids, the mole fractions of the unsaturated esters are lower than those of the saturated ones, regardless the chain length of the fatty acid. These experimental results are in good agreement with the calculations with TREPEX.